Publications by Type: Journal Article

BACKGROUND: Renal function may be a major determinant of resistin levels, since most studies revealed association between elevated resistin levels and decreased glomerular filtration rate (GFR) in patients with chronic kidney disease (CKD). The aim of the present study was to test the hypothesis whether serum resistin is associated with markers of malnutrition and inflammation in elderly non-diabetic adults in different stages of CKD including hemodialysis. METHODS: This was a cross-sectional study of 80 elderly patients divided in four groups of 20 patients each according to eGFR and matched for age (+/- 5 years) and gender. Patients with eGFR more than 1.5 mL/second served as controls. Multivariate regression was used to evaluate the association of resistin with eGFR, demographic, metabolic and inflammatory markers, and insulin resistance. Hematological, biochemical, and immunochemical analyses were performed using commercially available enzyme immunoassays. RESULTS: Our results showed that: 1) serum resistin levels were two times higher in patients with advanced CKD especially those undergoing hemodialysis compared to controls, 2) in univariate analysis, resistin levels correlated directly with Tumor Necrosis Factor-alpha (TNF-alpha), high sensitive C-Reactive Protein (hsCRP), and serum phosphate and inversely correlated with albumin, eGFR, and hematocrit levels. We failed to reveal any relationship between resistin levels and Homeostasis Model Assessment Score of Insulin Resistance (HOMA-IR), body mass index (BMI), cholesterol and leptin levels, 3) in multivariate analysis, only TNF-alpha (p < 0.001) and hsCRP (p = 0.032) were the most important independent determinants of serum resistin levels. CONCLUSIONS: These results indicate that resistin increases as GFR declines and may be involved in the malnutrition-inflammation state and the reverse epidemiology phenomenon present in elderly, non-diabetic patients with CKD.

Background: A cross sectional study to investigate HPV prevalence according to age and cytology.Methods: Women presenting to a gynaecological outpatient clinic for a Pap smear test were included in the study (n=3177). All women had cervical cytology and HPV testing.Results: Overall prevalence of any 24 HPV type analysed was 33.1{%} (95{%} CI 31.5{%} to 34.7{%}) and HPV 16 and HPV 42 were the most frequent (6.7{%} (95{%} CI 5.8{%} to 7.6{%}), 6.8{%} (95{%} CI 5.9{%} to 7.6{%})), in total samples. Multiple HPV infection rate was 12.9{%} (95{%} CI 11.8{%} to 14.1{%}). High risk HPV (hrHPV) types were present in 27.4{%} (95{%} CI 25.8{%} to 28.9{%}) of the samples.HPV prevalence was highest among 14 to 19 y.o (46.6{%} (95{%} CI 40.7{%}-52.4{%})) and second highest among 30-34 y.o. (39.7{%}, 95{%} CI 35.4{%}-44{%}). HPV 16 was highest among 20-24 (9.0{%} (95{%} CI 6.4{%}-11.6{%})) and second highest among 50 to 54 y.o. (6.3{%} (95{%} CI 2.9{%} to 9.8{%}).In Low-grade Squamous Intraepithelial Lesions (LgSIL) cytology samples, the most frequently detected hrHPV types were: 16 (14.5{%} (95{%} CI 12.1{%} to 16.9{%})), 51 (13.0{%} (95{%} CI 10.7{%} to 15.3{%})) and 53 (9.1{%} (95{%} CI 7.2{%} to 11.1{%})) and in High-grade Squamous Intraepithelial Lesions (HgSIL) were: HPV 16 (37.2{%} (95{%} CI 26.5{%} to 47.9{%})), HPV 51 (17.9{%} (95{%} CI 9.4{%} to 26.5{%})) and HPV 18 (12.8{%} (95{%} CI 5.4{%} to 20.2{%})).Conclusions: In the population studied, HPV 16 and 51 were the most frequent detected hrHPV types. HPV positivity, hrHPV and multiple HPV types infections were higher in young women, while HPV prevalence declined with increasing age and presented two peaks a higher (14-19 y.o.) and a lower one (30-34 y.o.) These results may contribute to the creation of a national screening programme. © 2013 Argyri et al.; licensee BioMed Central Ltd.

Apoptosis and necrosis are the two major modes of cell death, the molecular mechanisms of which have been extensively studied. Although initially thought to constitute mutually exclusive cellular states, recent findings reveal cellular contexts that require a balanced interplay between these two modes of cellular demise. Several death initiator and effector molecules, signaling pathways and subcellular sites have been identified as key mediators in both processes, either by constituting common modules or alternatively by functioning as a switch allowing cells to decide which route to take, depending on the specific situation. Importantly, autophagy, which is a predominantly cytoprotective process, has been linked to both types of cell death, serving either a pro-survival or pro-death function. Here we review the recent literature that highlights the intricate interplay between apoptosis, necrosis and autophagy, focusing on the relevance and impact of this crosstalk in normal development and in pathology. This article is part of a Special Section entitled: Cell Death Pathways.

Introduction: Renal impairment (RI) is a common complication of symptomatic myeloma; 20-40% of newly diagnosed patients present with moderate or severe RI and 10% of them may require dialysis. Immediate initiation of specific antimyeloma therapy is crucial in order to improve RI. Areas covered: There has been a significant improvement in the outcome of patients with RI over the past 15 years. The authors review current data on the role of antimyeloma therapy on the improvement or resolution of RI and the importance of novel regimens, especially those based on bortezomib. IMiDs-based regimens, conventional chemotherapy and high-dose therapy is also reviewed. The role of extrarenal free light chain removal, by means of plasma exchange or extended hemodialysis with the use of high cutoff dialysis membranes, is also discussed. Expert opinion: Bortezomib/dexamethasone-based regimens are the preferred regimens for most patients with multiple myeloma (MM) who present with RI, especially for newly diagnosed patients; however, other novel agents (thalidomide, lenalidomide) in combination with dexamethasone may also improve RI in several patients. Further investigation is needed for the clarification of the role of plasma exchange or extended high cutoff dialysis. Carfilzomib, which was recently approved, may also be a treatment choice for selected patients with relapsed MM and RI. © 2013 Informa UK, Ltd.

We consider series of M/M/m queues with strategic customer behavior. Customers arrive to the first queue and decide whether to enter the system or balk and, if they enter, up to which queue to proceed before departing. Each customer makes an independent decision, with the objective of maximizing her total net benefit, which is equal to the value of service minus a cost due to expected delay. We formulate the customer decision as a game and identify the unique symmetric Nash equilibrium strategy, which is expressed in a backward recursive form. We also analyze the problem of maximizing the total customer welfare and establish the relationship between the equilibrium and the welfare maximizing strategies. © 2011 Springer Science+Business Media, LLC.

The origin of hepatitis B virus (HBV) infection in humans and other primates remains largely unresolved. Understanding the origin of HBV is crucial because it provides a framework for studying the burden, and subsequently the evolution, of HBV pathogenicity with respect to changes in human population size and life expectancy. To investigate this controversy we examined the relationship between HBV phylogeny and genetic diversity of modern humans, investigated the timescale of global HBV dispersal, and tested the hypothesis of HBV-human co-divergence. We find that the global distribution of HBV genotypes and subgenotypes are consistent with the major prehistoric modern human migrations. We calibrate the HBV molecular clock using the divergence times of different indigenous human populations based on archaeological and genetic evidence and show that HBV jumped into humans around 33,600 years ago; 95% higher posterior density (HPD): 22,000-47,100 years ago (estimated substitution rate: 2.2 × 10(-6) ; 95% HPD: 1.5-3.0 × 10(-6) substitutions/site/year). This coincides with the origin of modern non-African humans. Crucially, the most pronounced increase in the HBV pandemic correlates with the global population increase over the last 5,000 years. We also show that the non-human HBV clades in orangutans and gibbons resulted from cross-species transmission events from humans that occurred no earlier than 6,100 years ago. CONCLUSION: Our study provides, for the first time, an estimated timescale for the HBV epidemic that closely coincides with dates of human dispersals, supporting the hypothesis that HBV has been co-expanding and co-migrating with human populations for the last 40,000 years. (HEPATOLOGY 2013).

PURPOSE: Acute appendicitis within a femoral hernia is a rare condition that was first described by Rene Jacques de Garengeot. In the present study, we summarize the existing evidence on de Garengeot's hernia, with special emphasis on its clinical presentation and diagnostic approach. METHODS: A thorough search of the English-language literature published between 1980 and 2011 was performed. Studies reporting cases of de Garengeot's hernia were selected using specific inclusion criteria (description of femoral hernia appendicitis, statement of patient demographics and symptoms, and statement of diagnostic tests performed). RESULTS: Thirty-one studies that encompassed 36 patients (28 women, mean age 71.5 years) with de Garengeot's hernia were included in our analysis. Patients presented with a right groin mass in 35 (97 %) cases. The mass was almost always painful (n = 35, 97 %), while 14 (39 %) of the patients were febrile. Mean duration of symptoms was 5.17 days. Fifty-six percent of the groin masses were erythematous. Leukocytosis was present in 67 % of the patients, and 25 patients underwent imaging investigation with X-ray (n = 11), Ultrasound (n = 5) or Computed Tomography (CT, n = 9). Twenty percent of the Ultrasound and 44 % of the CT studies were diagnostic, leading to an overall rate of 14 % of femoral hernia appendicitis preoperative diagnosis. Eighty-one percent of the patients underwent herniorrhaphy with sutures while a mesh was used in 19 %. Mean hospital stay was 6.23 days. CONCLUSION: Preoperative diagnosis of de Garengeot's hernia is difficult due to its atypical clinical presentation. Further surgical treatment depends on the surgeon's sound clinical judgment.

We introduce a theoretical model to scrutinize the conductivity of small polarons in 1D disordered systems, focusing on two crucial – as will be demonstrated – factors: the density of states and the spatial extent of the electronic wave function. The investigation is performed for any temperature up to 300 K and under electric field of arbitrary strength up to the polaron dissociation limit. To accomplish this task, we combine analytical work with numerical calculations.

Electrolysis of ultrapure water in a two-electrode cell with silver anode and conductive substrate (Si wafer) as a cathode leads to the formation of nanostructured silver layers deposited on cathode. In the process, the silver anode is electrochemically dissolved to silver cations, which react with water (or OH• radicals derived from water electrolysis) forming silver oxide nanoparticles, which fill the interelectrode space by electrophoretic movement, diffusion and convection induced by temperature effects of electrolysis. During the process the silver oxide nanoparticles are partially transformed into silver nanoparticles. On the cathode, silver cations and silver/silver oxide nanoparticles undergo reduction to form nanostructured silver film. The results of the present study open a new, extremely simple and ultra-low cost way to prepare nanostructured silver films on conducting and semiconducting substrates. The prepared nanosilver coated silicon substrates exhibit high performances as amperometric sensors for hydrogen peroxide and also as SERS substrates. © 2013 The Electrochemical Society.

In this paper we aim to contribute to the process of networking between theoretical frames in mathematics education by means of forging connections between Constructionism and Instrumental Theory to discuss a design for instrumentalisation. We specifically focus on instrumentalisation, i.e. the ways in which students make changes to digital artifacts and generate meanings in reference to these, as something which will not inevitably happen during activity with digital media. We discuss the issue of designing artifacts and corresponding activities in order to facilitate an instrumentalisation process which will be rich in the generation of mathematical meanings. We report findings from research aimed at shedding light on the meanings of angle in 3D space generated by 13 year olds students while using a specially designed Turtle Geometry microworld. The analysis indicates that connections between the two theories on the issue of designing for instrumentalisation enhances our efficiency to explore the instrumental genesis in technology-rich environments.

Limited information is available to describe the molecular epidemiology of HIV-1 in Bulgaria. To better understand the genetic diversity and the epidemiologic dynamics of HIV-1 we analyzed 125 new polymerase (pol) sequences from Bulgarians diagnosed through 2009 and 77 pol sequences available from our previous study from persons infected prior to 2007. Epidemiologic and demographic information was obtained from each participant and phylogenetic analysis was used to infer HIV-1 evolutionary histories. 120 (59.5%) persons were infected with one of five different HIV-1 subtypes (A1, B, C, F1 and H) and 63 (31.2%) persons were infected with one of six different circulating recombinant forms (CRFs; 01_AE, 02_AG, 04_cpx, 05_DF, 14_BG, and 36_cpx). We also for the first time identified infection with two different clusters of unique A-like and F-like sub-subtype variants in 12 persons (5.9%) and seven unique recombinant forms (3.5%), including a novel J/C recombinant. While subtype B was the major genotype identified and was more prevalent in MSM and increased between 2000-2005, most non-B subtypes were present in persons ≥45 years old. CRF01_AE was the most common non-B subtype and was higher in women and IDUs relative to other risk groups combined. Our results show that HIV-1 infection in Bulgaria reflects the shifting distribution of genotypes coincident with the changing epidemiology of the HIV-1 epidemic among different risk groups. Our data support increased public health interventions targeting IDUs and MSM. Furthermore, the substantial and increasing HIV-1 genetic heterogeneity, combined with fluctuating infection dynamics, highlights the importance of sustained and expanded surveillance to prevent and control HIV-1 infection in Bulgaria.

The study of atmospheric concentration levels at a local scale is one of the most important topics in environmental sciences. Multivariate analysis, fuzzy logic, and neural networks have been introduced in forecasting procedures in order to elaborate operational techniques for level characterization of specific atmospheric pollutants at different spatial and temporal scales. Particularly, approaches based on artificial neural networks (ANNs) have been proposed and successfully applied for forecasting concentration levels of PM10, NO2, SO2, CO, and O3. The present study explores the development and application of ANN models for forecasting, 24 h ahead, not only the daily concentration levels of PM10 but also the number of hours exceeding the PM10 concentration threshold during the day in five different regions within the greater Athens area (GAA). The ANN modeling was based on measurements and estimates of the mean daily PM10 concentration, the maximum hourly NO2 concentration, air temperature, relative humidity, wind speed, and the mode daily value of wind direction from five different monitoring stations for the period 2001-2005. The evaluation of the model performance showed the risk of daily PM10 concentration levels exceeding certain thresholds as well as the duration of the exceedances can be successfully predicted. Despite the limitations of the model, the results indicate that ANNs, when adequately trained, have considerable potential to be used for 1 day ahead PM10 concentration forecasting and the duration within the GAA. © Springer Science+Business Media Dordrecht 2013.

Hepatitis delta virus (HDV) infection is a usually severe type of viral hepatitis associated with increased mortality and rapid evolution to cirrhosis. Currently, treatment is limited to extended interferon administration and measurement of HDV RNA blood levels is essential to judge the response. The aim of this study was to develop a highly sensitive and reproducible real-time reverse transcriptase-polymerase chain reaction (real-time RT-PCR) for the quantitation of circulating HDV RNA of all clades (1-8), and assess its usefulness in the follow-up of patients. The amplification was combined with molecular beacon technology using the LightCycler 2.0 system. The assay was specific and showed linearity over a wide range from 13 to 13 x 10(10) copies/mL. The 95% detection limit was 43.2 copies/mL. Intra-assay reproducibility, as expressed by the coefficient of variation, ranged from 1.84 to 18.61%, whereas the corresponding estimates for the inter-assay variability ranged from 0.57 to 10.18%. Finally, the dynamic profiles of six patients regarding virological (HDV RNA, HBV DNA), biochemical and serological data were constructed. We were able to observe that most patients who were treated with an interferon-based regime showed a significant reduction in delta viremia. In conclusion, our real-time RT-PCR for HDV RNA quantification combines high sensitivity and reproducibility in a high dynamic range, can provide important information for patient management and can be a useful tool for monitoring the response to antiviral therapies.

Background:Accurate prediction of outcome for metastatic renal cell carcinoma (mRCC) patients receiving targeted therapy is essential. Most of the available models have been developed in patients treated with cytokines, while most of them are fairly complex, including at least five factors. We developed and externally validated a simple model for overall survival (OS) in mRCC. We also studied the recently validated International Database Consortium (IDC) model in our data sets.Methods:The development cohort included 170 mRCC patients treated with sunitinib. The final prognostic model was selected by uni- and multivariate Cox regression analyses. Risk groups were defined by the number of risk factors and by the 25th and 75th percentiles of the model's prognostic index distribution. The model was validated using an independent data set of 266 mRCC patients (validation cohort) treated with the same agent.Results:Eastern Co-operative Oncology Group (ECOG) performance status (PS), time from diagnosis of RCC and number of metastatic sites were included in the final model. Median OS of patients with 1, 2 and 3 risk factors were: 24.7, 12.8 and 5.9 months, respectively, whereas median OS was not reached for patients with 0 risk factors. Concordance (C) index for internal validation was 0.712, whereas C-index for external validation was 0.634, due to differences in survival especially in poor-risk populations between the two cohorts. Predictive performance of the model was improved after recalibration. Application of the mRCC International Database Consortium (IDC) model resulted in a C-index of 0.574 in the development and 0.576 in the validation cohorts (lower than those recently reported for this model). Predictive ability was also improved after recalibration in this analysis. Risk stratification according to IDC model showed more similar outcomes across the development and validation cohorts compared with our model.Conclusion:Our model provides a simple prognostic tool in mRCC patients treated with a targeted agent. It had similar performance with the IDC model, which, however, produced more consistent survival results across the development and validation cohorts. The predictive ability of both models was lower than that suggested by internal validation (our model) or recent published data (IDC model), due to differences between observed and predicted survival among intermediate and poor-risk patients. Our results highlight the importance of external validation and the need for further refinement of existing prognostic models. © 2013 Cancer Research UK. All rights reserved.

PURPOSE: In the Greek population of Epirus, exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) occur at a high prevalence. In this study, we validate a novel lysyl oxidase-like 1 (LOXL1) genotyping method, investigate the previously reported association of LOXL1 with XFS/XFG, and evaluate apolipoprotein E (APOE) and methylenetetrahydrofolate reductase (MTHFR) polymorphisms as genetic risk factors for both conditions in our population. METHODS: Blood samples were collected from 82 patients with XFG, 69 patients with XFS, 52 patients with primary open-angle glaucoma (POAG), and 107 controls. APOE and MTHFR 677C>T genotyping was performed from extracted genomic DNA with established methods. A novel methodology of real-time PCR and melting curve analysis was developed and validated to accurately genotype the LOXL1 G153D and R141L polymorphisms by using two different fluorescent channels of the LightCycler instrument (Roche) examining each SNP separately. RESULTS: No significant differences were observed for the APOE and MTHFR polymorphisms between the patients with XFS, the patients with XFG, and the control subjects. The APOE epsilon2 allele appears to be associated with elevated risk of POAG in our population. Our novel LOXL1 genotyping method was easy to perform, fast, and accurate. A statistically significant association was found for the LOXL1 gene with XFS/XFG in this Greek population. The association of XFS and XFG with G153D appeared to be less powerful in this population (XFS: odds ratio [OR]=2.162, p=0.039, XFG: OR=2.794, p=0.002) compared to other populations, and for R141L, the association was proven only with XFG (OR=3.592, p<0.001). Neither of the two LOXL1 SNPs was significantly associated with POAG. CONCLUSIONS: We confirmed the association between LOXL1 and XFS/XFG, but the APOE and MTHFR polymorphisms are not significant risk factors for the development of XFS/XFG in our population of patients from Epirus (Greece)

Despite the available prevention and early detection strategies, advanced squamous-cell carcinoma of the uterine cervix remains a major concern for public health. Systemic treatment with cisplatin, either in combination with external beam irradiation for locally advanced disease, or as monotherapy for recurrent/metastatic disease has been the cornerstone of treatment for more than two decades. Cisplatin has been also combined with a number of agents including paclitaxel, topotecan, gemcitabine, vinorelbine and ifosfamide, leading to encouraging response rates and increases in progression-free survival in a series of randomized phase III trials. Platinum-based triplets have been also tested, albeit at the cost of substantial toxicity. More recently, combinations with molecular agents targeting critical pathways in cervical malignant transformation are being assessed in clinical trials. In the current review, we discuss all recent advances in the systemic treatment of metastatic cervical cancer with emphasis on the results of large randomized phase III trials. Concerns regarding treatment-related toxicity in the context of co-morbidities and the need for potent predictive biomarkers for individualized treatment are also addressed. © 2012 Elsevier Ltd.

Despite the available prevention and early detection strategies, squamous-cell carcinoma of the uterine cervix is still diagnosed as locally advanced disease in a large proportion of patients. Treatment with cisplatin, in combination with external beam irradiation, has been the cornerstone of treatment in this setting for more than two decades. Induction chemotherapy strategies followed by concurrent chemo-radiation or surgery and pre-operative concurrent chemo-radiation have been recently implemented in clinical trials in an effort to optimize both local control and the occurrence of distant metastases. More recently, combinations of chemotherapy or radiotherapy with molecular agents targeting critical pathways in cervical malignant transformation are being assessed in clinical trials. In this paper, we review the role of cisplatin in the disease in the context of other potent radiosensitizers. We also discuss all recently implemented therapeutic modalities for the treatment of locally advanced cervical cancer with emphasis on the novel induction strategies. Concerns regarding treatment-related toxicity in the context of co-morbidities and the need for potent predictive biomarkers for individualized therapeutic approach are also addressed.

Stroke is one of the leading causes of long-term disability and mortality. Mounting evidence from observational studies suggests that among lifestyle factors, diet may be playing an important role for the prevention of stroke. Neuroimaging markers, particularly white matter hyperintensity (WMH) volume and brain infarcts (BI) are more sensitive measurements of cerebrovascular disease than clinical assessments. We reviewed published observational and clinical studies that evaluate the association between dietary factors and WMH and BI. The few existing studies examined only a handful individual nutrients or foods (dietary intake of alcohol, B vitamins, fish, choline, serum markers of antioxidants, and a few food groups, Mediterranean-style diet, and nutrient biomarker patterns. Findings from these studies are inconclusive either due to conflicting results from different studies or due to lack of replication. Further studies are necessary to replicate the existing findings. Many other foods or nutrients or dietary patterns may worth of investigation and longitudinal studies are needed.

OBJECTIVE: The behavioral and psychological symptoms associated with dementia (BPSD) are highly burdensome to caregivers. While BPSD consist of a wide variety of patient behaviors including depression, physical aggression, and paranoid delusions, it remains unclear whether specific symptoms have a differential impact on caregivers. The aims of this study were 1) to assess how individual BPSD, categorized based on how they may affect caregivers, impact depressive symptoms for dementia patient caregivers and 2) to test the pathways by which BPSD clusters impact caregiver depressive symptoms. DESIGN: Cross-sectional analysis of data from a longitudinal study of patients with Alzheimer disease and dementia with Lewy bodies. SETTING: Multiple U.S. dementia clinics. PARTICIPANTS: One hundred sixty patient-caregiver dyads. METHODS: Using multivariate generalized estimating equation logistic models, we analyzed the relationship between four BPSD clusters (patient depressive symptoms, accusatory/aggressive behaviors, nonthreatening psychotic symptoms, and difficult to manage behaviors) and caregiver depressive symptoms and assessed mediators of these relationships. RESULTS: Only the presence of patient depressive symptoms was associated with caregiver depression (odds ratio: 1.55; 95% confidence interval: 1.14-2.1). This relationship was mediated by caregiver report of both the symptom's impact on the patient and perceived burden to caregivers. CONCLUSION: Patient depressive symptoms may be the most important driver of the relationship between BPSD and caregiver depression. Research in this field should further test the effects of individual BPSD and also consider how symptoms may negatively impact caregivers by increasing burden and evoking empathy for the patient.

RX J0520.5-6932 is a recently confirmed Be/X-ray binary system in the LMC (see ATel #4748).

With these comments on the paper "Attitude of Physicians Towards Automatic Alerting in Computerized Physician Order Entry Systems", written by Martin Jung and co-authors, with Dr. Elske Ammenwerth as senior author [1], the journal wants to stimulate a broad discussion on computerized physician order entry systems. An international group of experts have been invited by the editor of Methods to comment on this paper. Each of the invited commentaries forms one section of this paper.

Extensive variation in land snail shell morphology has been widely documented, although few studies have attempted to investigate the ecological and evolutionary drivers of this variation. Within a comparative phylogenetic framework, we investigated the temporal and spatial evolution of the shell morphology of the Greek endemic land snail genus Codringtonia. The contribution of both inter- and intraspecies shell differentiation in the overall shell variability is assessed. The effect of climate, space, and evolutionary history on the shell variability was inferred using a variance partitioning framework. For Codringtonia species, intraspecies divergence of shell traits contributes substantially to the overall shell variability. By decomposing this variability, it was shown that the overall shell size of Codringtonia clades is phylogenetically constrained, related to early speciation events, and strongly affected by large-scale spatial variability (latitudinal gradient). The effect of climate on shell size cannot be disentangled from phylogeny and space. Shell and, to a larger extent, aperture shape are not phylogenetically constrained, and appear to be mostly related to conspecific populations divergence events. Shell shape is substantially explained by both climate and space that greatly overlap. Aperture shape is mainly interpreted by medium to small-scale spatial variables. © 2013 The Linnean Society of London, Biological Journal of the Linnean Society, 2013, ●●, ●●–●●.

Background: Significant controversy exists in the literature regarding the role of pregnancy in the prognosis of breast cancer. We designed a matched case-case study, matching pregnancy-associated breast cancer (PABC) cases with breast cancer cases for stage, age, and year of diagnosis. Patients and Methods: 39 consecutive cases of PABC were matched with 39 premenopausal cases of breast cancer. Univariate and multivariate survival analyses followed by adjustment for stage, grade, estrogen receptor status, and age at diagnosis, were performed. Results: Regarding overall survival (OS), univariate analysis pointed to longer OS in non-PABC cases vs. PABC cases. Accordingly, a more advanced stage predicted shorter survival. In the multivariate analysis, the independent aggravating effect mediated by pregnancy persisted. Interestingly, a post hoc nested analysis within PABC cases indicated that the 3rd trimester pointed to shorter OS. The aforementioned results on OS were also replicated during the examination of relapse-free survival. Conclusion: Implementing a matched case-case design, the present study points to pregnancy as a poor prognostic factor for breast cancer. © 2013 S. Karger GmbH, Freiburg.

Background: In hemodialysis (HD) patients, anemia relates to three main factors: insufficient production of erythropoietin; impaired management of iron; and decreased lifespan of red blood cells (RBCs). The third factor can relate to structural deterioration of RBCs due to extrinsic (extracorporeal circuit; biochemical activation and/or mechanical stress during dialysis) and intrinsic (uremic milieu; biochemical interference of the RBC membrane constituents with toxins) mechanisms. Herein, we evaluate information accessed with advanced imaging techniques at the cellular level. Methods: Atomic force and scanning electron microscopes were employed to survey intact RBCs (iRBCs) of seven HD patients in comparison to seven healthy donors. The extrinsic factor was investigated by contrasting pre- and post-HD samples. The intrinsic environment was investigated by comparing the microscopy data with the clinical ones. Results: The iRBC membranes of the enrolled HD patients were overpopulated with orifice-like (high incidence; typical size within 100-1,000 nm) and crevice-like (low incidence; typical size within 500-4,000 nm) defects that exhibited a statistically significant (P < 0.05) relative increase (+55% and +350%, respectively) in respect to healthy donors. The relative variation of the orifice and crevice indices (mean population of orifices and crevices per top membrane surface) between pre- and post-HD was not statistically significant (-3.3% and +4.5%, respectively). The orifice index correlates with the concentrations of urea, calcium, and phosphorus, but not, however, with that of creatinine. Conclusion: Extracorporeal circulation is not detrimental to the structural integrity of RBC membranes. Uremic milieu is a candidate cause of RBC membrane deterioration, which possibly worsens anemia.

Calcareous nannofossil biostratigraphy from Kotaphi Hill section allowed not only the biostratigraphic zonation of the Miocene units but also provided evidence for a distinct warm phase known as the Middle Miocene Climate Optimum (MMCO). Kotaphi Hill section is located in Agrokipia village (Nicosia region, Cyprus) and consists of cyclic marine deposits of the Pakhna Formation. High resolution sampling has been conducted and 84 samples were collected. Preliminary results indicated that several important calcareous nannofossil events can be consistently recognized along the studied section. High abundances of Discoaster druggii and Highest occurrence (HO) of Sphenolithus procerus suggest the presence of NN2 biozone while, LO of Sphenolithus belemnos has been used to recognize the base of biozone NN3. Upwards, Lowest Common Occurrence (LCO) of Sphenolithus heteromorphus marked the NN3-4 boundary-level. Biozone NN4 in Kotaphi Hill section is featured by high abundance of S. heteromorphus whereas total absence of the species together with the LO of Helicosphaera walbedorfensis mark the Paracme Beginning (PB) of S. heteromorphus interval. High abundance of warm indicators such as Discoasterids, S. heteromorphus, S. moriformis and Helicosphaera carteri observed in our material may partly reflect the warm phase of MMCO.

BACKGROUND: During 2011, a dramatic increase (1600%) of reported HIV-1 infections among injecting drug users (IDUs) was noted in Athens, Greece. We herein assess the potential causal pathways associated with this outbreak. METHODS: Our study employed high resolution HIV-1 phylogenetic and phylogeographic analyses. We examined also longitudinal data of ecological variables such as the annual growth of gross domestic product (GDP) of Greece in association with HIV-1 and HCV sentinel prevalence in IDUs, unemployment and homelessness rates and HIV transmission networks in Athens IDUs before and during economic recession (2008-2012). RESULTS: IDU isolates sampled in 2011 and 2012 suggested transmission networks in 94.6% and 92.7% of the cases in striking contrast with the sporadic networking (5%) during 1998-2009. The geographic origin of most HIV-1 isolates was consistent with the recently documented migratory waves in Greece. The decline in GDP was inversely correlated with annual prevalence rates of HIV and HCV and with unemployment and homelessness rates in IDUs (all p<0.001). The slope of anti-HCV prevalence in the sentinel populations of IDUs and in "new" drug injectors was found 120 and 1.9-fold (p = 0.007, p = 0.08 respectively) higher in 2008-2012 (economic recession) compared with 2002-2006. The median (25th, 75th) size of transmission networks were 34 (12, 58) and 2 (2, 2) (p = 0.057) in 2008-2012 and 1998-2007, respectively. The coverage of harm reduction services was low throughout the study period. CONCLUSIONS: Scaling-up harm reduction services and addressing social and structural factors related to the current economic crisis should be urgently considered in environments where HIV-1 outbreaks may occur.

BACKGROUND: During 2011, a dramatic increase (1600%) of reported HIV-1 infections among injecting drug users (IDUs) was noted in Athens, Greece. We herein assess the potential causal pathways associated with this outbreak. METHODS: Our study employed high resolution HIV-1 phylogenetic and phylogeographic analyses. We examined also longitudinal data of ecological variables such as the annual growth of gross domestic product (GDP) of Greece in association with HIV-1 and HCV sentinel prevalence in IDUs, unemployment and homelessness rates and HIV transmission networks in Athens IDUs before and during economic recession (2008-2012). RESULTS: IDU isolates sampled in 2011 and 2012 suggested transmission networks in 94.6% and 92.7% of the cases in striking contrast with the sporadic networking (5%) during 1998-2009. The geographic origin of most HIV-1 isolates was consistent with the recently documented migratory waves in Greece. The decline in GDP was inversely correlated with annual prevalence rates of HIV and HCV and with unemployment and homelessness rates in IDUs (all p<0.001). The slope of anti-HCV prevalence in the sentinel populations of IDUs and in "new" drug injectors was found 120 and 1.9-fold (p = 0.007, p = 0.08 respectively) higher in 2008-2012 (economic recession) compared with 2002-2006. The median (25th, 75th) size of transmission networks were 34 (12, 58) and 2 (2, 2) (p = 0.057) in 2008-2012 and 1998-2007, respectively. The coverage of harm reduction services was low throughout the study period. CONCLUSIONS: Scaling-up harm reduction services and addressing social and structural factors related to the current economic crisis should be urgently considered in environments where HIV-1 outbreaks may occur.

STUDY DESIGN: Comparative biomechanical study. OBJECTIVE: To determine whether an angular mismatch between the vertebral body replacement (VBR) endplate and the simulated foam vertebral endplate leads to accelerated subsidence in a cyclic compression model of the VBR-vertebra interface. SUMMARY OF BACKGROUND DATA: One of the main complications of the VBR surgery is postoperative subsidence and collapse of the VBR implant into the adjacent vertebral bodies. Although numerous factors affecting intervertebral cage subsidence have been cited, few studies have proposed factors responsible for VBR cage subsidence. METHODS: Hardwood blocks at 0-30-degree angles and polyurethane foam blocs have been used as base for this experimental setting. One end of the Synex (Synthes) expandable cage was attached to a material testing machine. The endplate of the implant was placed at a similar spot on the block in such a manner that there was an exact match between the Synex endplate and the foam block at 0 degrees, subsequent angled blocks would tilt the foam endplates by the 10-, 20-, and 30-degree increments as needed. Cyclic axial loads were applied in 9 load-unload cycles. RESULTS: Five samples were tested at each mismatch angle (0, 10, 20, and 30 degrees), for a total of 20 trials. Implant subsidence significantly increased for each 10-degree increase in mismatch angle. This effect, however, did not follow a uniform trend at all angles. The curve appeared exponential at 0 degree of angular mismatch, became linear at 10-20 degrees of mismatch, and then demonstrated some ability to resist load at 30 degrees, leading to a plateau at the higher loads. CONCLUSIONS: Increasing mismatch angles are an important factor in leading to increased cage subsidence into polyurethane blocks. Consequently, the incidence of subsidence in the clinical setting could be reduced by paying careful attention to ensuring that both the prosthetic and bony endplates are well apposed at the end of surgery.

The present work investigates the decadal morphological evolution of a microtidal, perched beach and the effect that beach rock formations can have on coastal morphology. Using historical and recent morphological observations from Ammoudara Beach on the island of Crete, Greece, and numerical modeling, the interaction of beach rock formation and retreating coastline are investigated. The principal feature of the morphological evolution of the coastal zone under investigation has been the transformation of a beach rock formation, initially attached to the shoreface (1950s), to a submerged reef that is aligned subparallel to the present-day shoreline. At present, the beach rock is attached to the shoreface at sea level at the western part of the beach, but it has evolved to a submerged reef toward the east, being approximately 40moff the shoreline at the central part and \~{}70moff the coastline at the eastern part of the beach. This kind of beach evolution is attributed to the interplay of natural hydrodynamic and sediment transport processes (that have been changing as the beach rock formation evolved to an offshore submerged reef) and to human intervention. The latter is exhibited mainly as changes in the sediment supply to the coastal zone (e.g., reduction in terrestrial freshwater/ sediment influx, deterioration of sand dune field, and arbitrary abstraction of beach material). After a period of readjustment of the nearshore hydrodynamics to the changing morphology and vice versa, it seems that, at present, Ammoudara Beach has attained a new morphodynamic equilibrium where the shore-parallel reef acts as a submerged breakwater.

Body size shapes the overall biology of organisms. We assessed the impact of size on temperature regulation in populations of normal-sized and large-bodied insular Mediterranean lizards (Podarcis gaigeae, Lacertidae). We hypothesized that large lizards would achieve higher body temperatures and thermoregulate more effectively than their smaller kin. Large- and small-bodied lizards share the same thermoregulation pattern, achieving similar body temperatures in the field. Large lizards, however, prefer higher set-point temperatures. Lizards in both populations thermoregulate effectively, but large lizards thermoregulated less effectively than normal sized lizards. The particular conditions at the islet that harbors the large-bodied population (harsh intraspecific competition) seem to account for this pattern.

Aim: The aim of the present study was to investigate the effects of the coach’s coaching and athletic experience on the four dimensions of Coaching Efficacy Scale (CES). Methods: The initial sample comprised 289 Greek male coaches, aged 39-6+6.9 years, from five different team sports (basketball, volleyball, football, handball, waterpolo). Combining the coaches’ high or low level of athletic and coaching experience, they were divided into four levels of experience profile. All coaches answered the Greek version of the 24-item questionnaire of Coaching Efficacy Scale during the final stages of the competition year of 2008-2009. Results: The MANOVA model revealed a significant effect of coaching and athletic experience on the dimensions of motivation, strategy and technique. Motivation is influenced only by athletic experience, while the presence of either coaching or athletic experience is sufficient to improve the efficacy of strategy. Conversely, the efficacy of technique can be significantly improved only if the coach has both adequate coaching and athletic experience. Finally the dimension of character building is not influenced by either the coaching or athletic experience. Conclusion: In conclusion, the three dimensions of CES (motivation, strategy and technique) are moderated by the coaches’ experience profile, with coaching and athletic experience acting specifically on each of the three dimensions.

The purpose of the present study was to investigate the effects of 6 weeks strength vs. ballistic-power (Power) training on shot put throwing performance in novice throwers. Seventeen novice male shot-put throwers were divided into Strength (N = 9) and Power (n = 8) groups. The following measurements were performed before and after the training period: shot put throws, jumping performance (CMJ), Wingate anaerobic performance, 1RM strength, ballistic throws and evaluation of architectural and morphological characteristics of vastus lateralis. Throwing performance increased significantly but similarly after Strength and Power training (7.0-13.5% vs. 6.0-11.5%, respectively). Muscular strength in leg press increased more after Strength than after Power training (43% vs. 21%, respectively), while Power training induced an 8.5% increase in CMJ performance and 9.0 - 25.8% in ballistic throws. Peak power during the Wingate test increased similarly after Strength and Power training. Muscle thickness increased only after Strength training (10%, p < 0.05). Muscle fibre Cross Sectional Area (fCSA) increased in all fibre types after Strength training by 19-26% (p < 0.05), while only type IIx fibres hypertrophied significantly after Power training. Type IIx fibres (%) decreased after Strength but not after Power training. These results suggest that shot put throwing performance can be increased similarly after six weeks of either strength or ballistic power training in novice throwers, but with dissimilar muscular adaptations. Key pointsBallistic-power training with 30% of 1RM is equally effective in increasing shot put performance as strength training, in novice throwers, during a short training cycle of six weeks.In novice shot putters with relatively low initial muscle strength/mass, short-term strength training might be more important since it can increase both muscle strength and shot put performance.The ballistic type of power training resulted in a significant increase of the mass of type IIx muscle fibres and no change in their proportion. Thus, this type of training might be used effectively during the last weeks before competition, when the strength training load is usually reduced, in order to increase muscle power and shot put performance in novice shot putters.

This paper presents an on-line research in Greek universities websites and an international literature review on electronic learning in the field of Health Informatics. The results reveal that there are a lot of e-learning programs offered by universities in Greece, but unfortunately none of them related to Health Informatics domain. On the other hand, the finding of the international literature shows that other European universities conduct e-learning studies in Health Informatics field. Future actions for the enrichment of e-learning service in Greek Health Informatics education are necessary.

In this study, we investigated the lateral electrical transport and photocurrent mechanisms in multilayers of two-dimensional arrays of silicon nanocrystals (SiNCs), grown on quartz substrates by low pressure chemical vapor deposition (LPCVD) of Si and thermal oxidation. At low voltages, electrical conduction was ohmic, whereas at higher voltages, it was space charge limited in the presence of traps. At temperatures higher than 200 K both dark current and photocurrent were determined by thermal activation of carriers across the energy band gap, with an activation energy depending either on the applied voltage or on illumination. At temperatures lower than 200 K, the rate of current variation with temperature was smaller as transport was realized by carrier hopping, via phonons, between trapping states within the energy band gap, located near in energy and around the Fermi level. However, at the same temperature range, photocurrent was independent of temperature, as it was determined by carrier hopping from higher energy states to progressively lower ones. From this analysis, carrier concentration, an effective carrier mobility and trap density were extracted. © 2013 American Institute of Physics.

Few layer graphene (FLG) is grown on single crystal Cu(111) by Chemical Vapor Deposition, and the electronic valence band structure is imaged by Angle-Resolved Photo-Emission Spectroscopy. It is found that graphene essentially grows polycrystalline. Three nearly ideal Dirac cones are observed along the Cu Γ ̄ K ̄ direction in k-space, attributed to the presence of ∼4°twisted three layer graphene with negligible interlayer coupling. The number of layers and the stacking order are compatible with Raman data analysis demonstrating the complementarity of the two techniques for a more accurate characterization of FLG. © 2013 AIP Publishing LLC.

High jumpers strive to maintain low body mass and may be at increased risk for inadequate nutrient intakes. Since there is no data on the nutritional status in this sport, this study aimed to evaluate the nutritional intake of elite high jumpers (7 males, 7 females). Athletes were in energy balance (energy intake was equal to energy expenditure and body mass was stable), but their energy intake was among the lowest reported for athletes (148±23 and 142±18 kJ/kg/day, for males and females). Carbohydrate intake of both males and females (3.6±0.8 g/kg/day) was low compared with recommended values, and diet was deficient in several micronutrients such as vitamin D (12% of dietary reference intake, DRI), vitamin E (34% DRI), folate (46% DRI), calcium (78% DRI) and iron (55% DRI, for females only). These low carbohydrate and micronutrient intakes may negatively affect training quality and adaptations and may jeopardize the athletes' health. © JPES.

High jumpers strive to maintain low body mass and may be at increased risk for inadequate nutrient intakes. Since there is no data on the nutritional status in this sport, this study aimed to evaluate the nutritional intake of elite high jumpers (7 males, 7 females). Athletes were in energy balance (energy intake was equal to energy expenditure and body mass was stable), but their energy intake was among the lowest reported for athletes (148±23 and 142±18 kJ/kg/day, for males and females). Carbohydrate intake of both males and females (3.6±0.8 g/kg/day) was low compared with recommended values, and diet was deficient in several micronutrients such as vitamin D (12% of dietary reference intake, DRI), vitamin E (34% DRI), folate (46% DRI), calcium (78% DRI) and iron (55% DRI, for females only). These low carbohydrate and micronutrient intakes may negatively affect training quality and adaptations and may jeopardize the athletes' health. © JPES.

High jumpers strive to maintain low body mass and may be at increased risk for inadequate nutrient intakes. Since there is no data on the nutritional status in this sport, this study aimed to evaluate the nutritional intake of elite high jumpers (7 males, 7 females). Athletes were in energy balance (energy intake was equal to energy expenditure and body mass was stable), but their energy intake was among the lowest reported for athletes (148±23 and 142±18 kJ/kg/day, for males and females). Carbohydrate intake of both males and females (3.6±0.8 g/kg/day) was low compared with recommended values, and diet was deficient in several micronutrients such as vitamin D (12% of dietary reference intake, DRI), vitamin E (34% DRI), folate (46% DRI), calcium (78% DRI) and iron (55% DRI, for females only). These low carbohydrate and micronutrient intakes may negatively affect training quality and adaptations and may jeopardize the athletes' health. © JPES.

We report our two-year experience in the endovascular treatment of brain aneurysms in relation to their parent artery wall. We prospectively recorded patients with intracranial aneurysms (107 ruptured - 38 unruptured) treated with coiling during a two-year period: 145 patients, 94 females and 51 males - mean age 56 years. The aneurysms were divided into side-wall (A) and bifurcation (B) groups. A total occlusion rate was noted in post-embolization angiograms in 101 aneurysms (70%) with a morbidity of 4%. No angiographic recurrence arose in the six-month follow-up. The two groups had a similar total occlusion rate (68.31% and 71.8% respectively), while the complication rate was 3% in group A and 4.7% in group B. Significant differences between the two groups were noted in the number of assisted coiling cases: 28 out of 60 cases (46.7%) in group A - 14 out of 85 cases (16.5%) in group B. Further statistical analysis showed strong dependencies for the type of endovascular procedure between the ruptured and unruptured aneurysms in both groups (p 0.000<0.05), but no dependencies between the aneurysm occlusion rate and the ruptured or non-ruptured aneurysms, or between the occlusion rate and the type of endovascular procedure (p 0.552>0.05 and 0.071>0.05 respectively). In conclusion, the anatomic relation of the aneurysm sac with the wall of the parent artery is important, as significant differences in endovascular practice, devices and techniques were noted between side-wall and bifurcation aneurysms.

Absorption of carbon dioxide and water in 1-butyl-3-methylimidazoliun tricyanomethanide ([C4C1im][TCM]) and 1-octyl-3- methylimidazolium tricyanomethanide ([C8C1im][TCM]) ionic liquids (ILs) was systematically investigated for the first time as a function of the H2O content by means of a gravimetric system together with in-situ Raman spectroscopy, excess molar volume (VE), and viscosity deviation measurements. Although CO2 absorption was marginally affected by water at low H2O molar fractions for both ILs, an increase of the H2O content resulted in a marked enhancement of both the CO2 solubility (ca. 4-fold) and diffusivity (ca. 10-fold) in the binary [CnC1im][TCM]/H2O systems, in contrast to the weak and/or detrimental influence of water in most physically and chemically CO2-absorbing ILs. In-situ Raman spectroscopy on the IL/CO2 systems verified that CO2 is physically absorbed in the dry ILs with no significant effect on their structural organization. A pronounced variation of distinct tricyanomethanide Raman modes was disclosed in the [CnC1im][TCM]/H2O mixtures, attesting to the gradual disruption of the anion-cation coupling by the hydrogen-bonded water molecules to the [TCM]- anions, in accordance with the positive excess molar volumes and negative viscosity deviations for the binary systems. Most importantly, CO2 absorption in the ILs/H2O mixtures at high water concentrations revealed that the [TCM]- Raman modes tend to restore their original state for the heavily hydrated ILs, in qualitative agreement with the intriguing nonmonotonous transients of CO 2 absorption kinetics unveiled by the gravimetric measurements for the hybrid solvents. A molecular exchange mechanism between CO2 in the gas phase and H2O in the liquid phase was thereby proposed to explain the enhanced CO2 absorption in the hybrid [C nC1im][TCM]//H2O solvents based on the subtle competition between the TCM-H2O and TCM-CO2 interactions, which renders these ILs very promising for CO2 separation applications. © 2013 American Chemical Society.

A sol-gel method based on the self-assembly technique with a nonionic surfactant was employed to synthesize visible-light-active CNTiO2 films with rough surface for drinking water treatment. The enhancement of photocatalytic activity of CNTiO2 films on the degradation of microcystin-LR (MC-LR) was subsequently evaluated under visible light irradiation. The films were characterized by XRD, ESEM, AFM, HRTEM, UV-vis diffuse reflectance spectroscopy (DRS), FT-IR, XPS, and porosimetry analysis. The results revealed that the physicochemical properties of the films, such as BET surface area, porosity, crystallite size and pore size distribution, could be controlled by adjusting the calcination temperature. Higher surface area, smaller crystallite size, narrow pore size distribution, and very high surface roughness (360 nm) were obtained for CN-codoped TiO2 films calcined at 400 °C. DRS showed that as-prepared CNTiO2 films exhibited higher absorption in the visible light region and a red shift in the band gap transition due to CN-doping. CNTiO2 films effectively degraded MC-LR under visible light irradiation compared to the reference film. In particular, the film calcined at 400 °C showed high mechanical stability during three consecutive cycles for MC-LR degradation. The enhancement on the photocatalytic activity of the CNTiO2 films under visible light irradiation was attributed to the synergistic effects of carbon and nitrogen doping as well as the high surface roughness of the prepared films. © 2013 Elsevier B.V.

Treatment outcomes of patients with cardiac stage III light chain (AL) amyloidosis remain poorly studied. Such cases have been excluded from most clinical studies due to perceived dismal prognosis. We report treatment outcomes of 346 patients with stage III AL amyloidosis from the United Kingdom, Italy, Germany, and Greece. Median overall survival (OS) was 7 months with OS at 3, 6, 12, and 24 months of 73%, 55%, 46%, and 29%, respectively; 42% died before first response evaluation. On an intention-to-treat basis, the overall hematologic response rate was 33%, including a complete response rate of 12%. OS rates at 12 and 24 months, respectively, for 201 response evaluable patients were 88% and 85% for complete responders, 74% and 53% for partial responders, and 39% and 22% for nonresponders. Forty-five percent of responders achieved an organ response. Amino-terminal fragment of brain-type natriuretic peptide (NT-proBNP) >8500 ng/L and systolic blood pressure (SBP) <100 mm Hg were the only factors that independently impacted OS and identified an especially poor prognosis subgroup of patients with a median OS of only 3 months. Outcome and organ function of stage III AL amyloidosis without very elevated NT-proBNP and low SBP is improved by a very good hematologic response to chemotherapy.

This paper presents a literature review on how health professionals are seeking health information using internet retrieval systems, databases. Publications present many attitude scales which evaluate the behavior of the users and the barriers that they face through the information research. On the following review are mentioned the characteristics that health professionals encounter on the use of computing. Also, is mentioned a number of problems which are associated with the information recourses such as reliability that were elicited and reviewed.

Estradiol (E2)-estrogen receptor (ER) actions are implicated in initiation, growth and progression of hormone-dependent breast cancer. Crosstalk between ERs, epidermal growth factor receptor (EGFR) and/or insulin-like growth factor receptor (IGFR) is critical for the observed resistance to endocrine therapies. Cell surface heparan sulfate proteoglycans (HSPGs) are principal mediators of cancer cell properties and the E2-ER pathway as well as those activated by EGFR and IGFR have significant roles in regulating the expression of certain cell surface HSPGs, such as syndecan-2 (SDC-2), syndecan-4 (SDC-4) and glypican-1. In this study, we therefore evaluated the role of EGFR-IGFR signaling on the constitutive expression and E2-mediated expression of ERs and HSPGs as well as the effect of E2-ERs and IGFR/EGFR-mediated cell migration in ERalpha+ (MCF-7) and ERbeta+ (MDA-MB-231) breast cancer cells using specific intracellular inhibitors of EGFR and IGFR. We report that the expression of ERalpha is mainly enhanced by IGFR, whereas ERbeta expression is mainly coordinated by EGFR. Moreover, constitutive SDC-2 expression in ERalpha+ and ERbeta+ cells is mainly mediated through the IGFR, whereas in ERalpha+ E2-treated cells EGFR is the active one. In contrast, SDC-4 expression is regulated by IGFR in the presence and absence of E2. E2 also seems to diminish the inhibitory effect of EGFR and IGFR inhibitors in breast cancer cell migration. These data suggest that the coordinated action of ERs with EGFR and/or IGFR is of crucial importance, providing potential targets for designing and developing novel multi-potent agents for endocrine therapies.

Background: The HER2 gene has been established as a valid biological marker for the treatment of breast cancer patients with trastuzumab and probably other agents, such as paclitaxel and anthracyclines. The TOP2A gene has been associated with response to anthracyclines. Limited information exists on the relationship of HER2/TOP2A gene status in the presence of centromere 17 (CEP17) gain with outcome of patients treated with anthracycline-containing adjuvant chemotherapy.Methods: Formalin-fixed paraffin-embedded tumor tissue samples from 1031 patients with high-risk operable breast cancer, enrolled in two consecutive phase III trials, were assessed in a central laboratory by fluorescence in situ hybridization for HER2/TOP2A gene amplification and CEP17 gain (CEP17 probe). Amplification of HER2 and TOP2A were defined as a gene/CEP17 ratio of >2.2 and ≥2.0, respectively, or gene copy number higher than 6. Additionally, HER2, TopoIIa, ER/PgR and Ki67 protein expression was assessed by immunohistochemistry (IHC) and patients were classified according to their IHC phenotype. Treatment consisted of epirubicin-based adjuvant chemotherapy followed by hormonal therapy and radiation, as indicated.Results: HER2 amplification was found in 23.7% of the patients and TOP2A amplification in 10.1%. In total, 41.8% of HER2-amplified tumors demonstrated TOP2A co-amplification. The median (range) of HER2, TOP2A and CEP17 gain was 2.55 (0.70-45.15), 2.20 (0.70-26.15) and 2.00 (0.70-26.55), respectively. Forty percent of the tumors had CEP17 gain (51% of those with HER2 amplification). Adjusting for treatment groups in the Cox model, HER2 amplification, TOP2A amplification, CEP17 gain and HER2/TOP2A co-amplification were not associated with time to relapse or time to death.Conclusion: HER2 amplification, TOP2A amplification, CEP17 gain and HER2/TOP2A co-amplification were not associated with outcome in high-risk breast cancer patients treated with anthracycline-based adjuvant chemotherapy.Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12611000506998 and ACTRN12609001036202. © 2013 Fountzilas et al.; licensee BioMed Central Ltd.

Through this research relative sea level changes from Late Holocene until the present day were studied, in the area of Skopelos and Alonnisos Islands. The study was accomplished through methodical underwater geomorphological research in both islands and led to the location of six and seven distinct submerged fossil shorelines, in Skopelos and Alonnisos accordingly, along the islands' coastline. Both islands have been affected during the last millennia, by repeated subsidence events, often of coseimic origin. The amount of each subsidence displacement was generally limited to one or a few decimetres, with recurrence intervals of some centuries.

We explore the derivation of interatomic exchange interactions in ferromagnets within density-functional theory (DFT) and the mapping of DFT results onto a spin Hamiltonian. We delve into the problem of systems comprising atoms with strong spontaneous moments together with atoms with weak induced moments. All moments are considered as degrees of freedom, with the strong moments thermally fluctuating only in angle and the weak moments thermally fluctuating in angle and magnitude. We argue that a quadratic dependence of the energy on the weak local moments magnitude, which is a good approximation in many cases, allows for an elimination of the weak-moment degrees of freedom from the thermodynamic expressions in favor of a renormalization of the Heisenberg interactions among the strong moments. We show that the renormalization is valid at all temperatures accounting for the thermal fluctuations and resulting in temperature-independent renormalized interactions. These are shown to be the ones directly derived from total-energy DFT calculations by constraining the strong-moment directions, as is done, e. g., in spin-spiral methods. We furthermore prove that within this framework the thermodynamics of the weak-moment subsystem, and in particular all correlation functions, can be derived as polynomials of the correlation functions of the strong-moment subsystem with coefficients that depend on the spin susceptibility and that can be calculated within DFT. These conclusions are rigorous under certain physical assumptions on the measure in the magnetic phase space. We implement the scheme in the full-potential linearized augmented plane wave method using the concept of spin-spiral states, considering applicable symmetry relations and the use of the magnetic force theorem. Our analytical results are corroborated by numerical calculations employing DFT and a Monte Carlo method.

INTRODUCTION: Sildenafil is the first effective oral treatment for male erectile dysfunction. Although it is generally accepted that its action is peripheral, it has been suggested that it influences central neural pathways that are involved in male sexual arousal. Recently, it was shown that local sildenafil administration enhances extracellular dopamine (DA) in the nucleus accumbens (NAcc). AIM: The aim of this study was to determine whether sildenafil administration alters dopaminergic and serotonergic activity in the NAcc and the medial preoptic area (mPOA) during a model of sexual arousal. METHODS: An acute (2 days) or chronic (21 days) sildenafil regimen (1 mg/kg) was administered intraperitoneally to male rats. Thirty minutes after the last sildenafil injection, all males were exposed to noncontact erection sessions by the presentation of inaccessible estrous females. Half of the males had previous experience of noncontact sexual encounter and the other half were exposed for the first time. MAIN OUTCOME MEASURES: Tissue levels of DA and its metabolites, 3,4-Dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), as well as serotonin (5-HT) and its metabolite 5-HIAA, were measured in the mPOA and NAcc with high-performance liquid chromatography with electrochemical detector. Dopamine ([DOPAC+HVA]/DA) and serotonin (5-HIAA/5-HT) turnovers were also calculated as indices of neurotransmission. RESULTS: In nontrained males, acute and chronic sildenafil treatment increased DA and 5-HT turnover rates in the mPOA and NAcc. In trained rats, acute sildenafil also increased DA and 5-HT turnover rates in both structures, whereas chronic treatment enhanced 5-HT turnover rate only in the mPOA and DA turnover rate only in the NAcc. CONCLUSIONS: Our data confirm that sildenafil enhances dopaminergic activity in the NAcc, extend these findings to the mPOA and furthermore, reveal sildenafil-induced effects on serotonergic activity in these brain regions as well. Therefore, present findings support an effect of sildenafil on central neural pathways that are involved in the control of sexual arousal.

INTRODUCTION: Sildenafil is the first effective oral treatment for male erectile dysfunction. Although it is generally accepted that its action is peripheral, it has been suggested that it influences central neural pathways that are involved in male sexual arousal. Recently, it was shown that local sildenafil administration enhances extracellular dopamine (DA) in the nucleus accumbens (NAcc). AIM: The aim of this study was to determine whether sildenafil administration alters dopaminergic and serotonergic activity in the NAcc and the medial preoptic area (mPOA) during a model of sexual arousal. METHODS: An acute (2 days) or chronic (21 days) sildenafil regimen (1 mg/kg) was administered intraperitoneally to male rats. Thirty minutes after the last sildenafil injection, all males were exposed to noncontact erection sessions by the presentation of inaccessible estrous females. Half of the males had previous experience of noncontact sexual encounter and the other half were exposed for the first time. MAIN OUTCOME MEASURES: Tissue levels of DA and its metabolites, 3,4-Dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), as well as serotonin (5-HT) and its metabolite 5-HIAA, were measured in the mPOA and NAcc with high-performance liquid chromatography with electrochemical detector. Dopamine ([DOPAC+HVA]/DA) and serotonin (5-HIAA/5-HT) turnovers were also calculated as indices of neurotransmission. RESULTS: In nontrained males, acute and chronic sildenafil treatment increased DA and 5-HT turnover rates in the mPOA and NAcc. In trained rats, acute sildenafil also increased DA and 5-HT turnover rates in both structures, whereas chronic treatment enhanced 5-HT turnover rate only in the mPOA and DA turnover rate only in the NAcc. CONCLUSIONS: Our data confirm that sildenafil enhances dopaminergic activity in the NAcc, extend these findings to the mPOA and furthermore, reveal sildenafil-induced effects on serotonergic activity in these brain regions as well. Therefore, present findings support an effect of sildenafil on central neural pathways that are involved in the control of sexual arousal.

Electronic patient records are important in patient data management. Aim of this 2-year study was to investigate the effect of an e-documentation system on the ED length of stay. The study compared three length of stay parameters with and without the use of a prototype e-documentation system. 99 of trauma patients were monitored with the use of the electronic system and 101 patients (control group) were monitored with traditional methods. Time between the admission and completion of care was significantly lower in the e-documentation group (100±92 minutes, control group: 149±29 minutes). Similar effect was also found to the total ED length of stay (127±93 vs. 206±41 minutes) and time between completion of care and ED exit (26±10 vs. 57±23 minutes). LOS was reduced with the e-documentation system. This is important for the quality of trauma patient care, since saving time during the first hours after the accident usually determines the outcome of trauma patients.

Assessment of bioequivalence (BE) for highly variable drugs is challenging. As within-subject variability increases, it becomes more difficult to prove BE, unless a large number of subjects is recruited. In order to face this problem, several approaches have been proposed. Among them, scaled BE limits (BEL) have recently attracted special attention because the European Medicines Agency and the US Food and Drug Administration adopted scaled approaches. Scaled BELs expand with variability using specific mathematical functions while include additional regulatory criteria in some cases. The aim of this study is twofold: (1) to provide a deeper insight into the dependence of scaled BELs on variability and (2) to unveil the underlying mathematical relationships. The comparative analysis of these BELs is implemented through algebraic manipulations and graphic illustrations. Special emphasis is placed on the ``absolute change{''} of each BEL and the ``relative change,{''} reflecting the portion of the relative to the maximum expansion of a BEL. This analysis reveals the causal differences between the different BELs on the mode of ``absolute{''} and ``relative{''} change. The results derived from this study are in agreement with the observed different performances of the various scaled BE approaches. (C) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:296-301, 2013

Asymptomatic multiple myeloma (AMM) is characterized by a constant risk of progression to symptomatic myeloma. To evaluate previously recognized risk factors and to identify high-risk features we analyzed 96 patients with AMM and at least 18 months of follow-up. The progression rate at 1,2, and 3 years was 8%, 15% and 26%, respectively, and the projected 5-year progression rate was 38%. Extensive bone marrow (BM) infiltration, abnormal free light chain (FLC) ratio and serum monoclonal (M)-protein≥3 gr/dl were the most significant factors for progression, whereas the type of heavy (IgG vs IgA) or light chain or immunoparesis of the uninvolved immunoglobulins were not. Abnormal marrow signal of magnetic resonance imaging of the spine was associated with a significant risk of progression (median 15 months, P=0.001). Extensive BM infiltration ≥60% (hazard ratio, HR: 13.7, P<0.001) and FLC ratio≥100 (HR: 9, P=0.003) independently identified a 'very high-risk' group, which included 12.5% of patients with AMM and who progressed ≤18 months from initial diagnosis. Development of anemia and/or lytic bone lesions were the most common features of symptomatic progression. In conclusion, there is a subgroup of patients who have a substantial risk of progression to symptomatic disease that can be detected at diagnosis (either by extensive BM infiltration≥60% or FLC ratio≥100) and may be considered for immediate treatment. © 2013 Macmillan Publishers Limited All rights reserved.

Microvillus inclusion disease (MVID), a rare severe congenital enteropathy characterized by intracytoplasmic microvillous inclusions and variable brush border atrophy on intestinal epithelial cells histology, is associated with defective synthesis or abnormal function of the motor protein myosin Vb encoded by the MYO5B gene. Although MYO5B gene is expressed in all epithelial tissues, it is unclear so far whether organs other than intestine are affected in MVID patients. We report a case of an infant with MVID who presented liver dysfunction, hematuria, and Pneumocystis jiroveci pneumonia during the course of the disease. It is discussed whether extraintestinal manifestations in this patient are secondary consequences of MVID or might be features of the disease associated with altered MYO5B function. Conclusions: MVID is classically included in the differential diagnosis of congenital diarrhea of secretory type. Recent advances in our knowledge regarding the role of myosin Vb in the pathophysiology of MVID is expected to clarify the clinical spectrum of the disease and the possible primary involvement of organs other than intestine.

In this paper we explore the interaction of discourse properties in the syntax of small clauses from a cross-linguistic perspective. In line with Chomsky’s (2007, 2008) idea that phasal properties should be extended to all phases, we argue for a strict parallelism between C-T and v-V, suggesting that v enters the derivation with both agreement and discourse features. These features may be inherited by V depending on the relevant language. Building on Miyagawa (2010) and Jimenez-Fernandez (2010), we claim that in Spanish and Greek, in contrast with English, both agreement and discourse features are inherited by V. This strategy accounts for the different order rearrangements detected in small clauses. The proposal can easily be extended to other languages such as Italian, Serbo-Croatian, Russian and Ukrainian, as opposed to French, Norwegian, Afrikaans and German.

INTRODUCTION: The First Aid Manual constitutes a detailed guide which contains useful information and suggested acts for potential pathogenic conditions in everyday life, given in an Android environment. AIM: The aim of the project is the capability of eliciting information regarding First Aid, by means of a widespread use device, such as smartphones. MATERIAL: For the conduction of the project a database was used, into which the information was incorporated, in order to be later reloaded into the Eclipse environment. It will there receive its final form as an executable file for android cellphones. RESULTS: The executable file axx.apk originated an application which, providing the user with 6 main categories (definition, epidemiological evidence, aggravating factors, symptoms, what to do, what to avoid, acts) gives them access to an easy navigation and enables them to provide first grade care, without the requirement of any previous experience. CONCLUSION: The more and more advanced needs of the modern lifestyle, combined with technological achievements have created a complex system of social fabric, having of course an effect also on the area of human accidents. Hence, First Aid information given in the environment of a mobile phone can prove to be a useful tool for anyone, in case of an accident.

The facile two-electron reduction of the phosphaalkyne tBuC=P by the U III cyclopentadienyl-pentalene mixed-sandwich complex [U(η5-C5Me5){η8-C 8H4(SiiPr3)2}] is reported. A single-crystal X-ray structural analysis of the diuranium(IV) product [(U{η5-C5Me5}{η8-C 8H4(SiiPr3)2})2(μ- tBuCP)] shows that it contains a slightly unsymmetrical, bridging μ-η2:η1- ligated phosphaalkene dianion. © 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Methane Hydrates are a new energy resource in the global energy market which has received extreme attention from a technological and geopolitical point of view. The reserve estimates exceed by far the overall estimates of all the other conventional energy reserves. With the existing technological know-how the exploitation of methane hydrates is expected to dominate the international energy market within the next 10-15 years. Methane hydrates have been mapped within the Hellenic Submarine Space and especially in the region of Kastellorizo, with whatever consequences it may have of geo-strategic nature for the political decisions of Greece and its relations with the neighboring countries and the delimitation of its EEZ.

Dental casts of 160 Greek subjects (80 males, 80 females) were scanned by a structured-light scanner. The upper and lower right first molar occlusal surface 3D meshes were processed using geometric morphometric methods. A total of 265 and 274 curve and surface sliding semilandmarks were placed on the upper and lower molar surfaces, respectively. Principal component analysis and partial least square analysis were performed to assess shape parameters. Molars tended to vary between an elongated and a more square form. The first two principal components (PCs), comprising almost 1/3 of molar shape variation, were related to mesiodistal-buccolingual ratios and relative cusp position. Distal cusps displayed the greatest shape variability. Molars of males were larger than those of females (2.8 and 3.2% for upper and lower molars respectively), but no shape dimorphism was observed. Upper and lower molar sizes were significantly correlated (r(2) = 0.689). Allometry was observed for both teeth. Larger lower molars were associated with shorter cusps, expansion of the distal cusp, and constriction of the mesial cusps (predicted variance 3.25%). Upper molars displayed weaker allometry (predicted variance 1.59%). Upper and lower molar shape covariation proved significant (RV = 17.26%, P < 0.0001). The main parameter of molar covariation in partial least square axis 1, contributing to 30% of total covariation, was cusp height, in contrast to the primary variability traits exhibited by PC1 and PC2. The aim of this study was to evaluate shape variation and covariation, including allometry and sexual dimorphism, of maxillary and mandibular first permanent molar occlusal surfaces.

This investigation aimed to quantify craniofacial variation in a sample of modern humans. In all, 187 consecutive orthodontic patients were collected, of which 79 were male (mean age 13.3, SD 3.7, range 7.5-40.8) and 99 were female (mean age 12.3, SD 1.9, range 8.7-19.1). The male and female subgroups were tested for differences in mean shapes and ontogenetic trajectories, and shape variability was characterized using principal component analysis. The hypothesis of modularity was tested for six different modularity scenarios. The results showed that there were subtle but significant differences in the male and female Procrustes mean shapes. Males were significantly larger. Mild sexual ontogenetic allometric divergence was noted. Principal component analysis indicated that, of the four retained biologically interpretable components, the two most important sources of variability were (i) vertical shape variation (i.e. dolichofacial vs. brachyfacial growth patterns) and (ii) sagittal relationships (maxillary prognatism vs. mandibular retrognathism, and vice versa). The mandible and maxilla were found to constitute one module, independent of the skull base. Additionally, we were able to confirm the presence of an anterior and posterior craniofacial columnar module, separated by the pterygomaxillary plane, as proposed by Enlow. These modules can be further subdivided into four sub-modules, involving the posterior skull base, the ethmomaxillary complex, a pharyngeal module, and the anterior part of the jaws.

 This paper presents a systemic analysis of the Iran-SyriaLebanon geopolitical sub-system within the frame of the Wider Middle East geo-complex and in light of the geopolitical factor of the Shiite Islamist movement. We consider that the Shiite Islamist movement, which is represented by Hezbollah in Lebanon and by proxy Shiite organizations in Iraq (Kataeb Hezbollah and Asa’ib Ahl al Haq), has been transformed, under Tehran’s management and direction, into an important power redistribution factor in the region. Turkey’s foreign policy is evaluated as unsuccessful and dangerous for the security of the state of Israel and the stability of the Middle Eastern geopolitical system, particularly in relation to Ankara’s support of radical Islamist groups operating inside Syria. Ankara’s policy is also considered as a trigger mechanism for the acceleration of secessionist and state-formation ambitions, such as in the case of the gradual autonomy of an ethnically Kurdish zone in the northeastern Syrian territory. In addition, the US-Russian initiative for the destruction of the chemical arsenal of the Assad regime is evaluated as beneficial for the regional stability. Equally, we evaluate the US-Iranian negotiation process as a strategically agile diplomatic maneuver from Washington’s part.

This paper presents a systemic analysis of the Greater Middle East Geo-complex, in the light of the geopolitical factor of the Islamist movement –both Shiite and Sunnite. We consider that the geostrategy practiced by the Anglo-Saxon actors of the Super-system of this specific geocomplex aims at the containment strategy of the Russian and Chinese actors from the Mediterranean Sub-system, along with their ally states of Qatar, Turkey, Saudi Arabia and some of the UAE (e.g. Abu Dhabi). Furthermore, with the rise to power of the Sunnite Islamist governments in the region, a “remote” threat is tried to be exerted against both of the aforementioned actors in order to increase the negotiating benefits of the dipole of the London-Washington Special Relationship, in view of the provoked redrawing of the borders of the former nation-state regime. Moreover, the US appear willing to create strong and permanent territorial strategic bases in the Middle East, in order to guarantee, both for Israel and the US, the strategic depth that is desirable for their security. We are making reference to the gradually developing strategic plan for the creation of an Independent Kurdistan, that would be able to serve Western security interests, as well as the energy-related interests of the Anglo-Saxon, and European oil consortia, but also Washington’s power projection to the Russian Near Abroad and the Chinese Northwest region of Xinjiang, increasing the power gap once again, in favor of the US, at the centre of the Rimland.

The geophysical and geological indications (pockmarks, gas chimneys, salt domes, etc.) that have been traced on the seabed using multi–beam echo–sounders and side–scan sonars, as well as the corresponding seismic surveys in the region South, South–west and South– east of Cyprus, as well as the corresponding international interest of investors, especially in the marine region of the Levantine Basin, lead to the conclusion that, from a geopolitical perspective, Greece must be urged to accelerate the consolidation of its sovereign rights and understand anew and in practical terms, that “Cyprus is not far away, not at all actually”. With respect to Kastellorizo and the submarine area of its EEZ, it is noted that de-tailed geophysical, bathymetric and sediment surveys have confirmed the fact that the region of the submarine Anaximander mountains presents active mud volcanoes, linked to the presence of gas hydrates. Samples of gas hydrates were collected using indicative samplings in mud volcanoes thoroughly mapped in sub–seabed layers of no more 1.5 m deep. Their form is “ice crystal”. New mud volcanoes were also discovered (“Athens” and “Thessaloniki”). Gas hydrates were found in samplings conducted on–board the M/V “Thessaloniki”. Based on preliminary assessments, the total capacity of the mud volcanoes of the Anaximander mountains complex is estimated between 2.56 6.40 c. km.1.

Back in 2010, during my presentation at the Conference of the Institute of Energy of South East Europe (ΙΕΝΕ) on 8 February 2010, I had stressed the importance for Greece to proclaim an EEZ, and clarified the pertinent diplomatic arguments, together with its geopolitical and geostrategic advantages. Later, this communication was published in the Press («Estia», 8 January 2011) and on the Internet (skai.gr). Also, the weekly Epikaira published a complete study, co–authored by me and Dr. G.–A. Sgouros, in the form of a special insert entitled The Greek EEZ and Kastellorizo: Principles of a Geopolitical Analysis (issue 82, 12–18.5.2011). There are comparative demarcations, using Turkey’s baseline, in two ways: one using the Voronoi method and one using the median line principle, as applied also by competent international organizations). The arguments expressed in these documents are still valid, considering there has been no change, on the part of Greece, on the practicalities of the EEZ. There have been, of course, many promises and declarations from politicians, as there have been “extremely good intentions”. In the meantime, many views were also circulated, which were extremely dangerous, on “how far is Kastellorizo located”, as well as relevant, equally unfortunate views. We tend to forget, as my colleague Th. Karyotis also points out, that “there are 137 states having a 200 nm EEZ”.

Europe’s “energy hunger” in the years to come will be such, as to oblige it to seek alternative fuel sources, far beyond the ones currently in use. A solution that presents itself as ideal is the supply of the continent with natural gas from the new reserves of Eastern Mediterranean. Turkey, a country outside this political game, reacts to such a perspective. However, the era does not seem to be favoring it.

BACKGROUND: Postoperative nausea and vomiting (PONV) are frequently encountered after thyroidectomy. For PONV prevention, selective serotonin 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists are considered one of the first-line therapy. We report on the efficiency of granisetron and tropisetron, with that of placebo on the prevention of PONV in patients undergoing total thyroidectomy. METHODS: One hundred twenty-seven patients were divided into three groups and randomized to receive intravenously, prior to induction of anesthesia, tropisetron 5 mg, or granisetron 3 mg, or normal saline. All patients received additionally 0.625 mg droperidol. All episodes of postoperative PONV during the first 24 h after surgery were evaluated. RESULTS: Nausea visual analogue scale (VAS) score was lower in tropisetron and granisetron groups than the control group at all measurements (P<0.01) except for the 8-h measurement for tropisetron (P=0.075). Moreover, granisetron performed better than tropisetron (P<0.011 at 4 h and P<0.01 at all other points of time) apart from the 2-h measurement. Vomiting occurred in 22.2%, 27.5%, and 37.5% in granisetron, tropisetron, and control groups, respectively (P=0.43). CONCLUSIONS: The combination of the 5-HT3 antagonists with droperidol given before induction of anesthesia is well tolerated and superior to droperidol alone in preventing nausea but not vomiting after total thyroidectomy.

We report a case of Azospirillum infection manifestating as granulomatous tenosynovitis of the right hand, in an immunocompetent middle-aged female. We highlight the unusual source of the infection, the diagnostic workup, as well as the treatment approach.

Grazing of goats on Mediterranean islets is a common practice. Its consequences on plant communities are well documented, although not on vertebrates. We aim to shed light on the effect of livestock farming on lizards by investigating five populations of the insular lizard, Podarcis gaigeae, differing in the duration and intensity of grazing. Data on grazing regime, invertebrate abundance, tick prevalence, infestation levels, gull nests and lizard densities were collected during a period of 6 consecutive years. Grazing had a negative impact on insect populations, thus decreasing food availability for lizards. Tick prevalence and infestation levels were higher in places of continuous grazing. Goat activity disturbed gulls, which avoid nesting, so depriving the islets of marine subsidies. As a consequence of all these factors, lizard densities were higher in ungrazed and lower in grazed biotopes. Grazing effects were more severe on islets communities than on the main island populations. Our data imply that management action should be taken to conserve the highly diverse islet populations.

The latest developments in the geopolitical complex of the Eastern Mediterranean and more in particular in the dipole of Greece and Turkey, correspond to the implementation stage for Turkey’s geostrategic goals. This is witnessed, inter alia, by the declarations of the Turkish Foreign Minister, A. Davutoğlu, during his latest visit in Greece, in March 2011. The sincerity of these declarations should be taken for granted, and should have been expected by the Greek diplomacy. This paper analyses the principles of a Geopolitical Analysis concerning the Greek EEZ.

Aims: To examine the biocontrol potential of multiactive Greek indigenous Streptomyces isolates carrying antifungal activity against Rhizoctonia solani that causes damping-off symptoms on beans.Methods and Results: A total of 605 Streptomyces isolates originated from 12 diverse Greek habitats were screened for antifungal activity against R. solani DSM843. Almost one-third of the isolates proved to be antagonistic against the fungus. From the above isolates, six were selected due to their higher antifungal activity, identified by analysing their 16S rRNA gene sequence and studied further. The obtained data showed the following: firstly, the isolates ACTA1383 and ACTA1557 exhibited the highest antagonistic activity, and therefore, they were selected for in vivo experiments using bean seeds as target; secondly, in solid and liquid culture experiments under optimum antagonistic conditions, the medium extracts from the isolates OL80, ACTA1523, ACTA1551 and ACTA1522 suppressed the growth of the fungal mycelium, while extracts from ACTA 1383 and ACTA1557 did not show any activity. Conclusions: These results corresponded important indications for the utility of two Greek indigenous Streptomyces isolates (ACTA1557 and ACTA1383) for the protection of the bean crops from R. solani damping-off symptoms, while four of them (isolates OL80, ACTA1523, ACTA1551 and ACTA1522) seem to be promising producers of antifungal metabolites. Significance and Impact of the Study: This is the first study on the biocontrol of R. solani using multiactive Streptomyces isolates originated from ecophysiologically special Greek habitats. Our study provides basic information to further explore managing strategies to control this critical disease.

Background: The mesenchymal-epithelial transition (MET) pathway is frequently altered in tumours. The purpose of our study was to determine the prognostic value of tumour MET expression levels in patients with triple-negative breast cancer (TNBC), in order to strengthen the rationale for targeted therapy of TNBC using MET inhibitors. Methods: We determined expression of MET in formalin-fixed paraffin-embedded surgical specimens of TNBC by immunohistochemistry. Recurrence-free and overall survival was analysed with Cox models adjusted for clinical and pathological factors.Results:Immunostaining for MET was classified as high in 89 of 170 (52%) tumours. MET expression was more frequently observed in G3 carcinomas (P=0.02) but was not significantly associated to any of the other clinical or pathological parameters. High MET expression predicted shorter survival of the patients. Multivariate Cox proportional hazards regression analyses identified MET to be an independent prognostic factor for recurrence (adjusted hazard ratio (HR) for recurrence 3.43; 95% confidence interval (CI) 1.65-7.12; P=0.001) and death (adjusted HR for death 3.74; 95% CI 1.65-8.46; P=0.002). Conclusion: These results provide further evidence that the MET pathway could be exploited as a target for TNBC. © 2013 Cancer Research UK. All rights reserved.

OBJECTIVE: Excess body weight has been implicated in the pathogenesis of myelodysplastic syndrome (MDS). We thus explored the role of serum fetuin-A reflecting ectopic hepatic fat deposition when storage capacity of adipocytes has been exceeded, free leptin reflecting overall fat mass and adiponectin reflecting visceral fat mass, all potential mediators of the effects of obesity on insulin resistance and, consequently, to MDS risk. MATERIALS & METHODS: In a hospital-based case-control study, we studied 101 cases with incident, histologically confirmed primary MDS and 101 controls matched on gender, age and date of diagnosis, between 2004 and 2007. Serum fetuin-A, adiponectin, leptin, leptin receptor, free leptin and insulin were determined. RESULTS: Higher serum fetuin-A, lower adiponectin and lower free leptin were all individually and independently associated with higher risk of MDS before and after controlling for matching and risk factors, such as age, gender, date of diagnosis, body mass index (BMI), family history of lymphohematopoietic cancer, smoking history and serum insulin. Interestingly, we have shown that these associations were prominent among overweight/obese individuals and persisted after controlling for BMI and serum insulin indicating that their effects are above and beyond insulinemia only. CONCLUSION: Elevated serum fetuin-A but lower adiponectin and free leptin are associated with higher risk of MDS particularly among overweight/obese individuals. These findings suggest that the association between excessive weight gain and the risk of MDS could be mediated by fetuin-A, adiponectin and free leptin, which may have potential clinical and preventive implications.

The dynamic and kinematic characteristics of surface explosive cyclones in the Mediterranean are examined and compared to those of ordinary cyclones. The cyclone detection is performed with the tracking algorithm developed in the University of Melbourne, using the 1° × 1° ERA-40 mean sea level pressure dataset for a 40 year period. It is verified that the explosive cyclogenesis in the Mediterranean is mainly a maritime phenomenon, occurring along the northern Mediterranean coast during the cold season. On the contrary, the ordinary cyclogenesis exhibits significant maxima in both continental and maritime environments throughout the year. The explosive cyclones are characterized by longer lifetime and greater propagation speed. They are larger and deeper in the eastern Mediterranean, whereas the ordinary cyclones are deeper in the western and larger in the eastern Mediterranean. The trend analysis revealed that both explosive and ordinary cyclones become less frequent in the Mediterranean basin, while there is a tendency for deeper ordinary cyclones over North Africa and shallower over the Aegean Sea and Cyprus. © 2013 Springer-Verlag Berlin Heidelberg.

BACKGROUND: Understanding HIV-1 subtype distribution and epidemiology can assist preventive measures and clinical decisions. Sequence variation may affect antiviral drug resistance development, disease progression, evolutionary rates and transmission routes. RESULTS: We investigated the subtype distribution of HIV-1 in Europe and Israel in a representative sample of patients diagnosed between 2002 and 2005 and related it to the demographic data available. 2793 PRO-RT sequences were subtyped either with the REGA Subtyping tool or by a manual procedure that included phylogenetic tree and recombination analysis. The most prevalent subtypes/CRFs in our dataset were subtype B (66.1%), followed by sub-subtype A1 (6.9%), subtype C (6.8%) and CRF02_AG (4.7%). Substantial differences in the proportion of new diagnoses with distinct subtypes were found between European countries: the lowest proportion of subtype B was found in Israel (27.9%) and Portugal (39.2%), while the highest was observed in Poland (96.2%) and Slovenia (93.6%). Other subtypes were significantly more diagnosed in immigrant populations. Subtype B was significantly more diagnosed in men than in women and in MSM > IDUs > heterosexuals. Furthermore, the subtype distribution according to continent of origin of the patients suggests they acquired their infection there or in Europe from compatriots. CONCLUSIONS: The association of subtype with demographic parameters suggests highly compartmentalized epidemics, determined by social and behavioural characteristics of the patients.

BACKGROUND: Neonatal immune neutropenia (NIN) is a rare, but potentially life-threatening, disorder caused by maternal alloantibodies recognizing paternal neutrophil antigens on fetal cells. Alloantibodies directed against the human neutrophil alloantigen system (HNA)-1 located on Fcγ receptor IIIb (FcγRIIIb) are most frequently implicated in NIN. In this report, we describe two cases of NIN with alloantibodies against FcγRIIIb, which did not match one of the known HNA-1a, -1b, or -1c specificities, but define a new antigen, HNA-1d. STUDY DESIGN AND METHODS: Neutrophil-reactive antibodies were detected by agglutination, microscopic immunofluorescence, and monoclonal antibody (MoAb)-specific immobilization of neutrophil antigens (MAIGA) assay. For epitope mapping of FcγRIIIb-reactive antibodies, recombinant chimeric variants of FcγRIIIb were used in the MAIGA assay. Genotyping of FCGR3B was performed by allele-specific polymerase chain reaction. RESULTS: Both mothers were typed FCGR3B*01+, *02-, *03+. Antibody screening revealed the presence of alloantibodies reactive with FcγRIIIb encoded by FCGR3B*02, but not with FcγRIIIb encoded by FCGR3B*03. MAIGA with recombinant, partly chimeric FcγRIIIb variants demonstrated that the antigen recognized by maternal antibodies is characterized by two amino acids, Ala78 and Asp82. Among the FCGR3B alleles, the sequence Ala78–-Asn82 is exclusively encoded by FCGR3B *02. CONCLUSION: A previously unrecognized second antigen, HNA-1d, is present on FcγRIIIb encoded by FCGR3B*02. This antigen is characterized by the sequence Ala78–-Asn82. It appears that only individuals carrying the HNA-1c phenotype can form anti-HNA-1d alloantibodies. The HNA-1 system now consists of four antigens encoded by three alleles.

Lenalidomide is a distinct second-generation immunomodulatory drug with multiple anticancer and immunomodulatory effects against hematologic malignancies, in particular multiple myeloma (MM). Dexamethasone synergistically enhances the anticancer effects of lenalidomide, and the combination of lenalidomide and dexamethasone (Len/Dex) is approved for the treatment of patients with relapsed and/or refractory MM. Results from pivotal phase III trials in this setting have demonstrated that Len/Dex extends overall survival compared with dexamethasone alone. Optimal clinical benefits are seen when Len/Dex is initiated at first relapse and continued, beyond best treatment response, until disease progression. Lenalidomide based regimens are also effective as induction therapy in patients with newly diagnosed MM. Importantly, lenalidomide has a predictable and manageable tolerability profile, with minimal neurotoxicity, allowing long-term administration. As the paradigm of myeloma disease continues to change, future studies will determine the efficacy of lenalidomide in novel combinations with potentially complimentary agents. © 2013 Elsevier Ireland Ltd.

PURPOSE: To address the factors that surgeons use to decide between 2 options for treatment when the evidence is inconclusive. METHODS: We tested the null hypothesis that the factors surgeons use do not vary by training, demographics, and practice. A total of 337 surgeons rated the importance of 7 factors when deciding between treatment and following the natural history of the disease and 12 factors when deciding between 2 operative treatments using a 5-point Likert scale between "very important" and "very unimportant." RESULTS: According to the percentages of statements rated very important or somewhat important, the most popular factors influencing recommendations when evidence is inconclusive between treatment and following the natural course of the illness were "works in my hands," "familiarity with the treatment," and "what my mentor taught me." The most important factors when evidence shows no difference between 2 surgeries were "fewer complications," "quicker recovery," "burns fewer bridges," "works in my hands" and "familiarity with the procedure." Europeans rated "works in my hands" and "cheapest/most resourceful" of significantly greater importance and "what others are doing," "highest reimbursement," and "shorter procedure" of significantly lower importance than surgeons in the United States. Observers with fewer than 10 years in independent practice rated "what my mentor taught me," "what others are doing" and "highest reimbursement" of significantly lower importance compared to observers with 10 or more years in independent practice. CONCLUSIONS: Surgeons deciding between 2 treatment options, when the evidence is inconclusive, fall back to factors that relate to their perspective and reflect their culture and circumstances, more so than factors related to the patient's perspective, although this may be different for younger surgeons. CLINICAL RELEVANCE: Hand surgeons might benefit from consensus fallback preferences when evidence is inconclusive. It is possible that falling back to personal comfort makes us vulnerable to unhelpful commercial and societal influences.

Purpose: Pharmacological inhibition of Hsp90 shows great promise in breast cancer treatment. This is the first systematic review to synthesize all available data and to evaluate the efficacy and safety of Hsp90 inhibitors in breast cancer. Methods: This study was performed in accordance with the PRISMA guidelines. Eligible articles were identified by a search of MEDLINE and ClinicalTrials.gov databases, using a predefined combination of the terms "breast", "cancer", "Hsp90", "inhibitors". Results: Overall, 19 articles (190 patients) were eligible. The greatest clinical activity has been observed on the field of HER2-positive metastatic breast cancer. However, accumulating data suggest that Hsp90 inhibitors may play a significant role in the treatment of triple negative and aromatase inhibitor-resistant breast cancer. Conclusion: In the last decade, the development of Hsp90 inhibitors has moved forward rapidly; however, no phase III trials have been conducted and none agent has been approved for use in the clinical practice. © 2013 Elsevier Ltd.

The objective of this work is the assessment of human thermal bioclimatic conditions in the Athens University Campus (AUC), including the Faculties and their respective Departments of the largest state institution of higher learning in Greece, and among the largest universities in Europe. The analysis of bioclimate was carried out, using the physiologically equivalent temperature (PET), which is based on the energy balance model of the human body. The meteorological data required for the calculation of PET concern hourly values of air temperature, relative humidity, wind speed and total solar radiation, for the time period 1999-2007. The recorded data sets were obtained from the meteorological station of the Laboratory of Climatology and Atmospheric Environment of the University of Athens. The results revealed the hours of the day in which thermal comfort or stress prevails, as well as the trends and variability of PET, for the studied period. Finally, the intense heat waves occurred during summer 2007 along with extreme cold conditions during December 2003-February 2004 were analyzed in terms of PET classes and compared to the respective average bioclimatic conditions of the study period. © 2013 Panagiotis T. Nastos and Andreas Matzarakis.

The development of hybrid materials exhibiting the simultaneous action of photocatalysis and membrane filtration can lead to improved water treatment processes. Photocatalysis has the potential to solve problems related to the fouling of membranes, the generation of toxic condensates, and the existence of very small and harmful organic pollutants in the permeate effluent. On the other hand membranes, especially the ceramic ones, are appropriate supports for the deposition of thin photocatalytic layers due to their high affinity with the photocatalyst (e.g., TiO2) and the possibility to further stabilize and activate the deposit with calcination. In addition, membranes exhibit two surfaces that come into contact with the polluted water and can be exploited for the photocatalyst deposition. Thus, with appropriate design of the membrane module it is possible to illuminate both membrane surfaces and develop very efficient photocatalytic ultrafiltration processes. Such processes must involve "double sided active photocatalytic membranes", where the pollutant undergoes two sequential photodegradation steps, the first in contact with the feed surface and the second in contact with the permeate surface of the membrane. Moreover the asymmetric pore structure of ceramic membranes assures proper mixing of the fluid and better contact with the porous photocatalytic layers. In this work double side active photocatalytic ultrafiltration (UF) membranes were developed by means of different chemical vapor deposition (CVD) techniques. Their performance in the elimination of methyl orange from water was elucidated by means of a prototype photocatalytic membrane reactor under continuous flow, applying UV irradiation on both membrane surfaces. Important aspects of membrane technology such as the evolution of water permeability and the energy consumption were compared with the standard and highly efficient nanofiltration (NF) process and the results indicated the beneficial effects of the hybrid UF/photocatalytic process. © 2013 American Chemical Society.

OBJECTIVE: The constellation of obesity, insulin resistance, and serum adipocytokine levels is associated with the risk and prognosis of postmenopausal breast cancer (PBC). Altered secretion of resistin may underlie the association between overweight/obesity and PBC. We thus explored the association of serum resistin with PBC, taking into account established risk factors, including adipokines and anthropometric, metabolic, and inflammatory markers. METHODS: In a case-control study, we studied 102 postmenopausal women with pathologically confirmed, incident invasive breast cancer and 102 control participants matched on age and time of diagnosis between 2003 and 2010 at the Veterans' Administration General Hospital of Athens (NIMTS Hospital). Serum resistin, adiponectin, leptin, metabolic (homeostasis model assessment score of insulin resistance) and inflammatory (tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein) parameters, and tumor markers (carcinoembryonic antigen and CA 15-3) were determined. RESULTS: The mean serum resistin level was significantly higher in case participants than in control participants (P < 0.001) in both univariate and multivariable analyses, adjusting for age, date of diagnosis, education, family history of cancer, use of exogenous hormones, alcohol consumption, smoking status, physical activity, reproductive markers, metabolic markers, anthropometric (body mass index and weight circumference) markers, inflammatory markers, and adipokines (odds ratio, 1.17; 95% CI, 1.03-1.34; P = 0.02). In case participants, resistin level correlated significantly with tumor markers and inflammatory parameters, but not with metabolic and anthropometric variables. CONCLUSIONS: Further prospective, longitudinal, and mechanistic studies are needed to determine whether hyperresistinemia is involved in the development of PBC or reflects changes during PBC progression and therefore could be used as a biomarker for PBC. Targeting resistin inhibition could be an effective therapeutic strategy in breast cancer by down-regulating the inflammatory microenvironment in breast tissue.

In human and experimental heart failure, the activity of the type 1 phosphatase is significantly increased, associated with dephosphorylation of phospholamban, inhibition of the sarco(endo)plasmic reticulum Ca(2+) transport ATPase (SERCA2a) and depressed function. In the current study, we investigated the molecular mechanisms controlling protein phosphatase-1 activity. Using recombinant proteins and complementary in vitro binding studies, we identified a multi-protein complex centered on protein phosphatase-1 that includes its muscle specific glycogen-targeting subunit GM and substrate phospholamban. GM interacts directly with phospholamban and this association is mediated by the cytosolic regions of the proteins. Our findings suggest the involvement of GM in mediating formation of the phosphatase-1/GM/phospholamban complex through the direct and independent interactions of GM with both protein phosphatase-1 and phospholamban. Importantly, the protein phosphatase-1/GM/phospholamban complex dissociates upon protein kinase A phosphorylation, indicating its significance in the beta-adrenergic signalling axis. Moreover, protein phosphatase-1 activity is regulated by two binding partners, inhibitor-1 and the small heat shock protein 20, Hsp20. Indeed, human genetic variants of inhibitor-1 (G147D) or Hsp20 (P20L) result in reduced binding and inhibition of protein phosphatase-1, suggesting aberrant enzymatic regulation in human carriers. These findings provide insights into the mechanisms underlying fine-tuned regulation of protein phosphatase-1 and its impact on the SERCA2/phospholamban interactome in cardiac function.

OBJECTIVES: Health informatics programs usually are evaluated by national accreditation committees. Not always are the members of these committees well informed about the international level of (education in) health informatics. Therefore, when a program is accredited by a national accreditation committee, this does not always mean that the program is of an international level. The International Medical Informatics Association (IMIA) has expertise in the field of education. The IMIA Recommendations on Education in Biomedical and Health Informatics guide curricula development. The goal of this article is to show that IMIA can also play the role of accreditation agency and to present the IMIA accreditation protocol and experiences obtained with it. METHODS: The accreditation procedure used in the Netherlands and Belgium was taken as a template for the design of the IMIA accreditation protocol. In a trial period of one and a half year the protocol is tested out on six health informatics programs. RESULTS: An accreditation protocol was designed. For judging the curriculum of a program the IMIA Recommendations are used. The institution has to write a self-assessment report and a site visit committee visits the program and judges its quality, supported by the self-assessment report and discussions with all stakeholders of the program. CONCLUSIONS: After having visited three programs it appears that the IMIA accreditation procedure works well. Only a few changes had to be introduced. Writing the self-assessment report already appears to be beneficial for the management of the program to obtain a better insight in the quality of their program.

A debate at the European Union Parliament was held on 13 November 2012 on the Impact of early diagnosis and control of chronic respiratory diseases on Active and Healthy Ageing (AHA). The debate was held under the auspices of the Cyprus Presidency of the European Union (2012) and represents a follow-up of the priorities of the Polish Presidency of the European Union (2011). It highlighted the importance of early life events on the occurrence of chronic respiratory diseases later in life and their impact on active and healthy ageing. Epidemiologic evidence was followed by actions that should be taken to prevent and manage chronic respiratory diseases in children. The debate ended by practical, feasible and achievable projects, demonstrating the strength of the political action in the field. Three projects will be initiated from this debate: The first will be a meeting sponsored by the Région Languedoc-Roussillon on the developmental origins of chronic diseases and ageing: from research to policies and value creation. The second project is being led by the WHO Collaborating Centre for Asthma and Rhinitis: Prevention of Asthma, Prevention of Allergy (PAPA). The third project is the GA(2)LEN sentinel network.

Abstract The overall biology of ectotherms is strongly affected by the thermal quality of the environment. The particular conditions prevailing on islands have a strong effect on numerous features of animal life. In this study we compared mainland and island populations of the lizard Lacerta trilineata and hypothesized that insularity would affect the thermoregulatory strategy. Continental habitats were of lower thermal quality, experiencing more intense fluctuations and had higher values of operative temperatures. Nevertheless mainland lizards selected for higher body temperatures in the lab and showed more effective thermoregulation during summer than their island peers. Lizards achieved similar body temperatures in the field in both types of habitat, underlining the importance of predation as a potential factor to mainland lizards that failed to reach their higher thermal preferences. Both island and mainland populations of L. trilineata have been adapted to their thermal environment, supporting the labile view on the evolution of thermal physiology for this species.

BACKGROUND: Influenza is associated with an increased risk for serious illness, hospitalization, and mortality in infants aged <6 months. However, influenza vaccines are not licensed for administration in this age group. The study evaluated the effectiveness of postpartum influenza vaccination of mothers and household members in infants. METHODS: The influenza vaccine was offered to mothers and household members of neonates born or hospitalized in 3 hospitals prior to the 2012-2013 season. Mothers were contacted every 2 weeks during the influenza season, and data regarding the onset of fever and/or respiratory symptoms in infants, healthcare seeking, hospitalization, and administration of antibiotics were collected. RESULTS: The study group consisted of 553 mothers who delivered 573 neonates. The influenza vaccine was administered to 841 of 1844 (45.6%) household contacts. Vaccination coverage rates ranged between 41.9% for neonates siblings and 49% for mothers. Five hundred thirty infants were analyzed for vaccine effectiveness. For outcomes in the infant, postpartum maternal vaccination had 37.7% effectiveness against acute respiratory illness (ARI), 50.3% against a febrile episode, 53.5% against influenza-like illness (ILI), 41.8% against related healthcare seeking, and 45.4% against administration of antibiotics. Multiple logistic regression analyses showed that maternal influenza vaccination was significantly associated with a decreased probability for febrile episodes, ARIs, and/or ILIs in infants, related healthcare seeking, and/or administration of antibiotics during the influenza season. Vaccination of other household contacts had no impact. CONCLUSIONS: Maternal postpartum vaccination against influenza was associated with a significant reduction of influenza-related morbidity, healthcare seeking, and antibiotic prescription in infants during the influenza season.

MYCN is a well-known oncogene overexpressed in different human malignancies including neuroblastoma, rhabdomyosarcoma, medulloblastoma, astrocytoma, Wilms' tumor, and small cell lung cancer. While neuroblastoma is one of the most common childhood malignancies, in adults it is extremely rare and its treatment is based on pediatric protocols that take into consideration stage and genotypic features, such as MYCN amplification. Although neuroblastoma therapy has evolved, identification of early stage patients who need chemotherapy continues to pose a therapeutic challenge. The emerging prognostic role of MYCN phenotype of this disease is currently under investigation as it may redefine MYCN amplified subgroups. We describe an unusual case of adult neuroblastoma with MYCN amplification diagnosed incidentally and discuss possible therapeutic dilemmas.

Objective: The prognosis for patients with platinum-resistant advanced ovarian cancer remains poor. The impact of approved agents on survival has not been clarified during the last decade. We studied survival trends during the last 15 years in platinum-resistant patients treated with cytoreductive surgery followed by paclitaxel/platinum chemotherapy. Methods: Patients with epithelial ovarian, fallopian or peritoneal cancer, stages III/IV and platinum-resistant disease after first-line chemotherapy with paclitaxel/platinum were included. They were grouped according to the period of chemotherapy: group A 31/3/1995-31/12/2001 (n = 56) and Group B 1/1/2002-24/12/2008 (n = 57). In order to compensate for the difference in follow-up between the 2 groups, we performed minimum follow-up (MFU) analyses by considering as cases only women who had an event within 3 years of follow-up. Patients with no events for up to 3 years were censored at that time. Results: MFU analyses showed that median overall survival (OS) was significantly longer in group B: 12.3 vs. 17.5 months (p = 0.012). This was due to a doubling of the median OS after relapse: 5.7 vs. 10.9 months (p = 0.0180). Multivariate Cox regression indicated group and histology as factors statistically significantly associated with OS. Following relapse, patients in group B were predominantly treated with liposomal doxorubicin and gemcitabine, and patients in group A were treated with platinum compounds, docetaxel and oral etoposide (p < 0.001). Conclusions: The introduction of novel agents without cross-resistance to platinum or taxanes has improved the prognosis of platinum-resistant patients. © 2012 S. Karger AG, Basel.

The objective of this study is to present and analyse the indoor and outdoor temporal variability of the particulate matters of different sizes (namely: PM10, with diameter less than 10 μm; PM7, with diameter less than 7 μm; PM2.5, with diameter less than 2.5 μm and PM1, with diameter less than 1 μm) found in Athens, Greece. Four detectors were used for indoor and outdoor recordings. More specifically, the indoor recordings were performed in seminar rooms, full of students attending lectures, at the University of Athens and the Technological Education Institute of Piraeus. Findings of this research show that on one hand, the indoor particulate matter concentrations remained at lower levels than the thresholds set by the European Council Directives, but on the other hand, the outdoor particulate matter concentrations exceeded the thresholds many times. © The Author(s) 2012 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

The effect of the electrochemical anodization growth process on the development of self-organized TiO2 nanotube (NT) films and their efficiency as photoelectrodes in dye sensitized solar cells (DSCs) has been comparatively investigated, by keeping constant the total anodization charge. Slow and rapid potentiostatic anodization processes were accordingly compared to the galvanostatic one, while a two step potentiostatic-galvanostatic technique was applied for the first time for the growth of TiO2 NT arrays, as a step forward in relation to the existing potentiostatic-potentiostatic (P-P) technique. Scanning electron microscopy and Raman spectroscopy verified the wide diversity in the morphological and structural characteristics of the TiO 2 NTs obtained by the different anodization modes. The novel approach of galvanostatic tube growth on a potentiostatically patterned Ti foil provided the most uniform TiO2 nanotubular films with clean top surface exempt of nanograss or cracks over extended areas. Evaluation of the TiO 2 NTs performance as photoelectrodes in DSC devices showed distinct differences of their electrical parameters that reflected finely the underlying structure/morphology variations of the different anodic oxidation conditions. Galvanostatic TiO2 NT films presented the most favorable (open-ordered) structure for DSC photoelectrodes with superior electrical performance, essentially impaired by a relatively low fill factor that requires improvement by appropriate post-treatment. Furthermore, despite the marked differences in morphology, the TiO2 NT photoelectrodes exhibited comparable overall performance (of the order of 4%), with only exception the P-P samples which presented slightly lower (about 25%) photovoltaic efficiency. These results indicate that the anodization charge is a critical factor that effectively controls the nanotubes behavior when they are used as photoelectrodes in DSCs. © 2013 Elsevier Ltd.

Fruit and vegetable intake in children remains below recommendations in many countries. The long-term effects of early parental feeding practices on fruit and vegetable intake are not clearly established.|The purpose of the current study was to examine whether early feeding practices influence later fruit and vegetable intake in preschool children.|The study used data from 4 European cohorts: the British Avon Longitudinal Study of Parents and Children (ALSPAC), the French Etude des Déterminants pre et postnatals de la santé et du développement de l'Enfant study, the Portuguese Generation XXI Birth Cohort, and the Greek EuroPrevall study. Fruit and vegetable intake was assessed in each cohort by food-frequency questionnaire. Associations between early feeding practices, such as breastfeeding and timing of complementary feeding, and fruit and/or vegetable intake in 2-4-y-old children were tested by using logistic regressions, separately in each cohort, after adjustment for infant's age and sex and maternal age, educational level, smoking during pregnancy, and maternal fruit and vegetable intake.|Large differences in early feeding practices were highlighted across the 4 European cohorts with longer breastfeeding duration in the Generation XXI Birth Cohort and earlier introduction to complementary foods in ALSPAC. Longer breastfeeding duration was consistently related to higher fruit and vegetable intake in young children, whereas the associations with age of introduction to fruit and vegetable intake were weaker and less consistent across the cohorts. Mothers' fruit and vegetable intake (available in 3 of the cohorts) did not substantially attenuate the relation with breastfeeding duration.|The concordant positive association between breastfeeding duration and fruit and vegetable intake in different cultural contexts favors an independent specific effect.

Knowledge, research, and innovation are of crucial importance for the competitiveness of an economy and a recipe for economic development not only for developed and developing countries, but also for entities surviving a political abnormality, such as the Palestinian territories. As Palestinians are currently planning for their future viable state, the policy and decision makers should formulate relevant science, technology, and innovation policies that encourage the different national sectors to utilize the available innovation potentials and the experience and support of other countries, for developing a competitive economy. Conducting and analyzing a community innovation survey on two major Palestinian industrial sectors, namely quarrying and stone fabrication and the food and beverages sector, brought about very promising indicators and showed high innovative potentials in both sectors. Employment, export, and revenues are clearly improved in innovative enterprises. Lack of cooperation between the industrial sector and the higher education and research and development institutions is found to be a major problem that should be tackled in order to strengthen the enterprises’ ability to innovate.

Knowledge, research, and innovation are of crucial importance for the competitiveness of an economy and a recipe for economic development not only for developed and developing countries, but also for entities surviving a political abnormality, such as the Palestinian territories. As Palestinians are currently planning for their future viable state, the policy and decision makers should formulate relevant science, technology, and innovation policies that encourage the different national sectors to utilize the available innovation potentials and the experience and support of other countries, for developing a competitive economy. Conducting and analyzing a community innovation survey on two major Palestinian industrial sectors, namely quarrying and stone fabrication and the food and beverages sector, brought about very promising indicators and showed high innovative potentials in both sectors. Employment, export, and revenues are clearly improved in innovative enterprises. Lack of cooperation between the industrial sector and the higher education and research and development institutions is found to be a major problem that should be tackled in order to strengthen the enterprises’ ability to innovate.

Nanostructured modified TiO2 (m-TiO2) was synthesized using the gel combustion method based on the calcination of an acidified alkoxide solution mixed with urea. The materials were characterized by Raman, FT-IR and UV-vis diffuse reflectance spectroscopies, transmission (TEM) and scanning electron microscopies (SEM), X-ray photoelectron spectroscopy (XPS) and electron paramagnetic resonance (EPR), in comparison with reference material untreated with urea (ref-TiO2). The effect of both the urea content and calcination temperature were optimized, providing the optimal absorption threshold of 2.19eV for solar light harvesting. The photocatalytic performance of the m-TiO2 powder was tested for the degradation of methylene blue (MB) azo dye under UVA (350-365nm), visible (440-460nm), and daylight (350-750nm) illumination. The hybrid inorganic/organic material shows exceptional physicochemical properties and significant photocatalytic activity, especially in the visible, attributed to sensitization of the TiO2 by a thin porous layer of carbonacious species in controlled core-shell morphology. © 2012 Elsevier B.V.

The reactions of [Ir(κ3N,N,H-Tai)(COD)] and [Ir(κ3N,N,H-PhBai)(COD)] (where Tai = HB(azaindolyl)3 and PhBai = Ph(H)B(azaindolyl) 2) with carbon monoxide result in the formation of Z-type iridium-borane complexes supported by 7-azaindole units. Analysis of the reaction mixtures involving the former complex revealed the formation of a single species in solution, [Ir(η1-C8H 13){κ3N,N,B-B(azaindolyl)3}(CO) 2], as confirmed by NMR spectroscopy. In the case of the PhBai complex, a mixture of species was observed. A postulated mechanism for the formation of the new complexes has been provided, supported by computational studies. Computational studies have also focused on the reaction step involving the migration of hydrogen from boron (in the borohydride group) to the iridium center. These investigations have demonstrated a small energy barrier for the hydrogen migration step (ΔG298 = 10.3 kcal mol-1). Additionally, deuterium labeling of the borohydride units in Tai and PhBai confirmed the final position of the former borohydride hydrogen atom in the resulting complexes. The importance of the "third azaindolyl" unit within these transformations and the difference in reactivity between the two ligands are discussed. The selective coordination properties of this family of metallaboratrane complexes have also been investigated and are discussed herein. © 2013 American Chemical Society.

Unveil the properties of a two-stage design (TSD) for bioequivalence (BE) studies. A TSD with an upper sample size limit (UL) is described and analyzed under different conditions using Monte Carlo simulations. TSD was split into three branches: A, B1, and B2. The first stage included branches A and B1, while stage two referred to branch B2. Sample size re-estimation at B2 relies on the observed GMR and variability of stage 1. The properties studied were % BE acceptance, % uses and % efficiency of each branch, as well as the reason of BE failure. No inflation of type I error was observed. Each TSD branch exhibits different performance. Stage two exhibits the greatest % BE acceptances when highly variable drugs are assessed with a low starting number of subjects (N-1) or when formulations differ significantly. Branch A is more frequently used when variability is low, drug products are similar, and a large N-1 is included. BE assessment at branch A is very efficient. The overall acceptance profile of TSD resembles the typical pattern observed in single-stage studies, but it is actually different. Inclusion of a UL is necessary to avoid inflation of type I error.

The epidemiology of chronic viral infections, such as those caused by Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV), is affected by the risk group structure of the infected population. Risk groups are defined by each of their members having acquired infection through a specific behavior. However, risk group definitions say little about the transmission potential of each infected individual. Variation in the number of secondary infections is extremely difficult to estimate for HCV and HIV but crucial in the design of efficient control interventions. Here we describe a novel method that combines epidemiological and population genetic approaches to estimate the variation in transmissibility of rapidly-evolving viral epidemics. We evaluate this method using a nationwide HCV epidemic and for the first time co-estimate viral generation times and superspreading events from a combination of molecular and epidemiological data. We anticipate that this integrated approach will form the basis of powerful tools for describing the transmission dynamics of chronic viral diseases, and for evaluating control strategies directed against them.

The epidemiology of chronic viral infections, such as those caused by Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV), is affected by the risk group structure of the infected population. Risk groups are defined by each of their members having acquired infection through a specific behavior. However, risk group definitions say little about the transmission potential of each infected individual. Variation in the number of secondary infections is extremely difficult to estimate for HCV and HIV but crucial in the design of efficient control interventions. Here we describe a novel method that combines epidemiological and population genetic approaches to estimate the variation in transmissibility of rapidly-evolving viral epidemics. We evaluate this method using a nationwide HCV epidemic and for the first time co-estimate viral generation times and superspreading events from a combination of molecular and epidemiological data. We anticipate that this integrated approach will form the basis of powerful tools for describing the transmission dynamics of chronic viral diseases, and for evaluating control strategies directed against them.

The aim of the International Myeloma Working Group was to develop practice recommendations for the management of multiple myeloma (MM) -related bone disease. An interdisciplinary panel of clinical experts on MM and myeloma bone disease developed recommendations based on published data through August 2012. Expert consensus was used to propose additional recommendations in situations where there were insufficient published data. Levels of evidence and grades of recommendations were assigned and approved by panel members. Bisphosphonates (BPs) should be considered in all patients with MM receiving first-line antimyeloma therapy, regardless of presence of osteolytic bone lesions on conventional radiography. However, it is unknown if BPs offer any advantage in patients with no bone disease assessed by magnetic resonance imaging or positron emission tomography/computed tomography. Intravenous (IV) zoledronic acid (ZOL) or pamidronate (PAM) is recommended for preventing skeletal-related events in patients with MM. ZOL is preferred over oral clodronate in newly diagnosed patients with MM because of its potential antimyeloma effects and survival benefits. BPs should be administered every 3 to 4 weeks IV during initial therapy. ZOL or PAM should be continued in patients with active disease and should be resumed after disease relapse, if discontinued in patients achieving complete or very good partial response. BPs are well tolerated, but preventive strategies must be instituted to avoid renal toxicity or osteonecrosis of the jaw. Kyphoplasty should be considered for symptomatic vertebral compression fractures. Low-dose radiation therapy can be used for palliation of uncontrolled pain, impending pathologic fracture, or spinal cord compression. Orthopedic consultation should be sought for long-bone fractures, spinal cord compression, and vertebral column instability.

Excess body weight constitutes a worldwide health problem with epidemic proportions impacting on the risk and prognosis of several disease states including malignancies. It is believed that the metabolic changes associated with weight gain, particularly visceral obesity, and physical inactivity could lead to dysfunctional adipose and muscle tissues causing insulin resistance, low-grade chronic inflammation and abnormal secretion of adipokines and myokines. The complex paracrine and endocrine interconnection between adipokines and myokines reflects a yin-yang balance with important implications in processes such as lipolysis control, insulin sensitivity and prevention from obesity-driven chronic low-grade inflammation and cancer promotion through anti-inflammatory adipokines and myokines. Furthermore, the complex pathophysiology of cancer cachexia is based on the interplay between muscle and adipose tissue mediated by free fatty acids, various adipokines and myokines. The purpose of this editorial is to explore the role of the adipose and muscle tissue interplay in carcinogenesis, cancer progression and cachexia, and to examine the mechanisms underpinning their association with malignancy. Understanding of the mechanisms connecting the interplay of adipokines and myokines with cancer pathophysiology is expected to be of importance in the development of therapeutic strategies against cancer cachexia. Advances in the field of translational investigation may lead to tangible benefits to obese and inactive persons who are at increased risk of cancer as well as to cancer patients with cachexia.

Leptomeningeal carcinomatosis (MC) represents an uncommon, but devasting manifestation of metastatic breast cancer. This is the first systematic review/pooled analysis to synthesize all available data evaluating the efficacy and safety of intrathecal (IT) administration of trastuzumab for the treatment of MC in HER2-positive breast cancer patients. This study was performed in accordance with the PRISMA guidelines. A total of 13 articles (17 patients) were eligible. The mean age of patients at IT trastuzumab administration was 48.2 years (SD 8.4, range 38-66). The mean total dose was 399.8 mg (SD 325.4, range 35-1,110 mg). IT trastuzumab alone or as part of combination therapies seemed to be safe; no serious adverse events were reported in 88.2 % of cases. In 68.8 % of cases, a significant clinical improvement was observed, while stabilization or progression of the disease was noticed in 31.2 % of cases. Cerebrospinal fluid (CSF) response was noted in 66.7 % of cases. The median overall survival was 13.5 months, whereas the median central nervous system progression-free survival (CNS-PFS) was 7.5 months. In 23.5 % of cases, IT trastuzumab was administered beyond CNS progression with a response noticed in 75 % of cases and a CNS-PFS of 9.4 months. The cumulative dose of IT trastuzumab given was 1,040 mg (SD 697.9, median 1,215, range 55-1,675). The protective effect of prior radio- or neurosurgery upon CNS-PFS was sizeable but did not reach formal statistical significance (HR 0.28, 95 % CI 0.06-1.37). Clinical improvement (HR 0.14, 95 % CI 0.02-0.91) and CSF response (HR 0.09, 95 % CI 0.01-0.89) were associated with longer CNS-PFS. IT trastuzumab administration seems to represent a safe and in some cases effective option for the treatment of HER2-positive breast cancer patients with leptomeningeal involvement. However, clinical trials are urgently needed to establish the definite role of IT trastuzumab in HER2-positive metastatic breast cancer patients with MC. © 2013 Springer Science+Business Media New York.

The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project.

The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project.

The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project.

The volatile constituents of 22 samples of commercial beers (lager, ale, and lambic) were isolated using adsorption resin XAD-4 and analyzed by gas chromatography, using mass-spectrometric detection. The presence of 63 volatile components was examined in each sample. Major common compounds identified in all of the studied samples were 2-methylpropanol (0.77-12.9%), 3-methylbutanol (32.0-55.5%), phenylethanol (18.7- 58.8%), and tyrosol (0.69-5.82%), expressed as TIC percent. Most other components were found in various concentrations but their presence was not uniformly distributed in all the studied beers. One of the minor volatile compounds, 2-(3H)-benzoxazolone, was found only in beers made with wheat malt. Additionally, for the first time, tryptophol acetate was identified as beer constituent. Finally, principal component analysis of the volatile compounds was able to discriminate the group of beers containing wheat. © 2013 American Society of Brewing Chemists, Inc.

Innovative redox electrolytes for dye-sensitized solar cells (DSCs) were prepared using binary mixtures of 1-methyl-3-propylimidazolium iodide (MPII) with 1-alkyl-methylimidazolium tricyanomethanide, CνmimTCM (ν = 2, 4, 6, 8) ionic liquids (ILs) to lower the high viscosity of MPII. The investigation of the physicochemical properties of the IL blends as a function of temperature has shown that both density and viscosity strongly depend on the kind of the Cνmim cation in the mixture. The corresponding Raman spectra were dominated by the vibrational modes of the IL components in an additive way and confirmed the absence of any specific interaction, independent of the Cν alkyl chain length. The electrochemical properties (triiodide diffusion coefficients, specific conductivity), determined in symmetrical thin layer cells using polarization and electrochemical impedance spectroscopy (EIS) measurements, have shown that both diffusion and conductivity decreased with increasing viscosity, and further confirmed the electrolytes' compatibility with the cathode. Incorporation of the novel electrolytes in DSC devices revealed a systematic dependence of the cell photovoltaic performance on the alkyl chain length of CνmimTCM; the maximum power conversion efficiency exceeded 5 and 6.5% under 1 and 0.1 sun AM 1.5 G illumination, respectively, for the ionic liquid with the shortest alkyl chain. The solar cells were further characterized by EIS (IMPS) spectroscopy, exploring charge recombination dynamics and identifying conduction band edge shifts. Solidification of the electrolytes with silica nanoparticles, demonstrated that the ionic liquid electrolytes with long chain length (ν > 4) not only retain their efficiencies, but also exhibit a 22% efficiency enhancement, which is most pronounced for the electrolytes employing ionic liquids with the longest (hexyl- and octyl-) alkyl chains. © 2013 The Royal Society of Chemistry.

Central nervous system (CNS) involvement in patients with primary mediastinal large B-cell (PMLBCL) lymphoma is a rare event, occurring in approximately 6% of patients, on the basis of the review of the literature prior to induction of Rituximab. The aim of this retrospective study was to describe the incidence of CNS relapse among 100 consecutive patients with PMLBCL who were treated with R-CHOP±RT in comparison to patients treated with CHOP±RT (n=45) in 11 hospitals in Greece. Two patients experienced a CNS relapse, representing an overall frequency of 2.0% in R-CHOP treated patients and a 2-year actuarial incidence of 2.3%. Both patients had isolated CNS relapses. The incidence of CNS relapse after CHOP without Rituximab was 2/45 (4.4%) for a 2-year actuarial incidence of 7.5% (p=0.29). Again, both patients had isolated CNS relapses. Parenchymal-only localizations accounted for 3/4 cases. Risk factors for CNS involvement could include leukocytosis, poor performance status and higher age-adjusted International Prognostic Index, although their impact was weakened by competing risk survival analysis. Both patients relapsing after R-CHOP required CNS radiotherapy to achieve a complete remission and be forwarded to high-dose therapy and autologous stem cell transplantation: They are both alive and disease-free 18 and 23months after CNS relapse. Both cases relapsing after CHOP without Rituximab were salvaged by CNS radiotherapy (one also received intrathecal chemotherapy) entering long-term remissions. In conclusion, CNS relapses are rare in PMLBCL tending to be isolated in the CNS, probably reflecting the persistence of latent CNS disease than dissemination of resistant disease. The impact of Rituximab in reducing CNS relapses remains unknown. Established risk factors for CNS involvement in aggressive lymphomas may not be helpful in assessing the risk of CNS recurrence in this disease. Routine CNS prophylaxis is not probably required in PMLBCL. © 2012 John Wiley & Sons, Ltd.

This review starts with an introduction on the theoretical aspects of biopharmaceutics and developments in this field from mid-1950s to late 1970s. It critically addresses issues related to fundamental processes in oral drug absorption such as the complex interplay between drugs and the gastrointestinal system. Special emphasis is placed on drug dissolution and permeability phenomena as well as on the mathematical modeling of oral drug absorption. The review ends with regulatory aspects of oral drug absorption focusing on bioequivalence studies and the US Food and Drug Administration and European Medicines Agency guidelines dealing with Biopharmaceutics Classification System and Biopharmaceutic Drug Disposition Classification System. (C) 2013Wiley Periodicals, Inc. and the American Pharmacists Association

Conventional experimental models of respiratory allergy have contributed greatly to our current knowledge of the pathophysiology of allergic airway diseases; nevertheless, they are contingent upon unnatural sensitization techniques, entailing adjuvant-aided intraperitoneal (i.p) administration of antigen. Currently, there is a growing appreciation of the impact of tolerance mechanics in the pathophysiology of respiratory allergy. Thus, inasmuch as adjuvants exert a robust tolerance-modifying action, a transition from the conventional method of experimental sensitization to one that is more naturally and clinically relevant becomes important. We therefore opted to survey the literature and identify agents that could interfere with sensitization mechanics following non-adjuvant-aided airway exposure of laboratory rodents to aeroallergen. GM-CSF was found to exert robust Th2-polarizing action in this setting. Conversely, IL-10 fulfilled an important, albeit not so clear-cut, tolerance-favoring role; TGF-β was also identified as a likely instigator of tolerogenesis. The role of Notch signaling in the sensitization versus tolerance dilemma appeared to be important but diverse. Collectively, these factors appeared to profoundly and diversely modulate the balance between tolerance and sensitization in naturally relevant experimental models of allergic airway disease.

Kiwifruit is a common cause of food allergy. Symptoms range from mild to anaphylactic reactions.|We sought to elucidate geographic differences across Europe regarding clinical patterns and sensitization to kiwifruit allergens. Factors associated with the severity of kiwifruit allergy were identified, and the diagnostic performance of specific kiwifruit allergens was investigated.|This study was part of EuroPrevall, a multicenter European study investigating several aspects of food allergy. Three hundred eleven patients with kiwifruit allergy from 12 countries representing 4 climatic regions were included. Specific IgE to 6 allergens (Act d 1, Act d 2, Act d 5, Act d 8, Act d 9, and Act d 10) and kiwifruit extract were tested by using ImmunoCAP.|Patients from Iceland were mainly sensitized to Act d 1 (32%), those from western/central and eastern Europe were mainly sensitized to Act d 8 (pathogenesis-related class 10 protein, 58% and 44%, respectively), and those from southern Europe were mainly sensitized to Act d 9 (profilin, 31%) and Act d 10 (nonspecific lipid transfer protein, 22%). Sensitization to Act d 1 and living in Iceland were independently and significantly associated with severe kiwifruit allergy (odds ratio, 3.98 [P = .003] and 5.60 [P < .001], respectively). Using a panel of 6 kiwifruit allergens in ImmunoCAP increased the diagnostic sensitivity to 65% compared with 20% for skin prick tests and 46% ImmunoCAP using kiwi extract.|Kiwifruit allergen sensitization patterns differ across Europe. The use of specific kiwifruit allergens improved the diagnostic performance compared with kiwifruit extract. Sensitization to Act d 1 and living in Iceland are strong risk factors for severe kiwifruit allergy.

Proposition initiale: Avant toute tentative de définition métathéorique lakatienne de l’analyse géopolitique systémique et de définition ontologique de ses notions structurelles, nous admettrons que l’approche théorique de l’analyse géopolitique systémique contemporaine, laquelle est de nature interdisciplinaire et se fonde sur la géographie politico-économique1 participe sur un pied d’égalité à l’ensemble des approches théoriques qui constituent le programme de recherche géopolitique néo-positiviste.

The anatomy of the dorsiventral, amphistomatic leaf of Papaver rhoeas was investigated. It was a simple structure possessing large epidermal cells having their vacuole impregnated with glycoproteins which varied in texture, forming a dense, hard core in the middle of the vacuole. Slender rays of cisternae radiated from the dense central core to the cell wall. Thin-walled palisade cells presented a unique, lobed shape probably creating larger surfaces for gas exchange. Mesophyll cells secreted phenolics, condensed tannins, alkaloids, terpene containing steroids and sesquiterpenes. P. rhoeas although being a therophyte, has adopted some structural features common in mediterranean phanerophytes. © 2013 Taylor & Francis Group, LLC.

The dorsiventral, amphistomatic, hairy leaf of Pelargonium odoratissimum was lacking the variety of the anatomical features considered advantages for the Mediterranean plant life compared to the leaf of most Mediterranean xerophytes. Conversely, it had a well-equipped and intensely functioning secretory apparatus. Light, scanning, and transmission electron microscopy were employed to investigate the leaf structure while histochemical reactions traced the nature of the secreted metabolites. The numerous trichomes of the leaf were very active in producing phenolics, terpenes, and flavonoids mixed in a fragrant essential oil accumulated in an ovoid chamber at the top of each secreting hair. In-vitro cell cultures may be used for the production of novel compounds from low-cost precursors. © 2013 Taylor & Francis Group, LLC.

The MM-015 trial assessed the effect of lenalidomide-based therapy on health-related quality of life. Patients (n=459) with newly diagnosed multiple myeloma aged 65 years or over were randomized 1:1:1 to nine 4-week cycles of lenalidomide, melphalan, and prednisone, followed by lenalidomide maintenance; or lenalidomide, melphalan, and prednisone, or melphalan and prednisone, with no maintenance therapy. Patients completed health-related quality of life questionnaires at baseline, after every third treatment cycle, and at treatment end. Health-related quality of life improved in all treatment groups during induction therapy. Patients receiving lenalidomide maintenance had the most pronounced improvements, Global Health Status/Quality of Life (P<0.05), Physical Functioning (P<0.01), and Side Effects of Treatment (P<0.05) out of 6 pre-selected health-related quality of life domains. More patients receiving lenalidomide maintenance achieved minimal important differences (P<0.05 for Physical Functioning). Therefore, lenalidomide, melphalan, and prednisone, followed by lenalidomide maintenance, improves health-related quality of life in patients with newly diagnosed multiple myeloma. (Clinicaltrials.gov identifier NCT00405756). © 2013 Ferrata Storti Foundation.

Since its discovery as an adipocyte-secreted hormone, leptin has been found to impact food intake, energy homeostasis, and metabolism through its effects on the central nervous system and peripheral organs. Recent research indicates that leptin may also be involved in cognition, immune function, and bone metabolism. These findings place leptin at the intersection of neuroendocrinology and metabolism, and possibly immune function, and render it an appealing therapeutic target for several niche areas of unmet clinical need. Current evidence regarding classic and emerging roles of leptin as well as the pros and cons of its potential clinical use are summarized herein.

Leptin is an adipocyte-secreted hormone that has been proposed to regulate energy homeostasis as well as metabolic, reproductive, neuroendocrine, and immune functions. In the context of open-label uncontrolled studies, leptin administration has demonstrated insulin-sensitizing effects in patients with congenital lipodystrophy associated with relative leptin deficiency. Leptin administration has also been shown to decrease central fat mass and improve insulin sensitivity and fasting insulin and glucose levels in HIV-infected patients with highly active antiretroviral therapy (HAART)-induced lipodystrophy, insulin resistance, and leptin deficiency. On the contrary, the effects of leptin treatment in leptin-replete or hyperleptinemic obese individuals with glucose intolerance and diabetes mellitus have been minimal or null, presumably due to leptin tolerance or resistance that impairs leptin action. Similarly, experimental evidence suggests a null or a possibly adverse role of leptin treatment in nonlipodystrophic patients with nonalcoholic fatty liver disease. In this review, we present a description of leptin biology and signaling; we summarize leptin's contribution to glucose metabolism in animals and humans in vitro, ex vivo, and in vivo; and we provide insights into the emerging clinical applications and therapeutic uses of leptin in humans with lipodystrophy and/or diabetes.

Cet article, basé sur les sources des textes sacrés du Coran ainsi que sur des textes de kanunistes importants de l’Islam, soutient le point de vue que le seul qui a le pouvoir absolu de déclarer le Djihad (en arabe égyptien: Gehad) c’est le Calife de l’Oumma qui a été choisi selon la Loi Sacrée (Shari’a). Cependant, puisque dans les circonstances actuelles l’Oumma des croyants (des musulmans) n’a pas la structure califale et donc n’a pas du calife, personne ne peut déclarer le Gehad selon les dispositions de la Loi Sacrée (Shari’a). Ainsi, «la Réouverture des Portes de l’Idjtihad (en arabe égyptien: Edgehad)» que les islamistes tentent et leur indifférence pour l’idjma’a (en arabe égyptien: egma’a) des kanunistes ne permet pas le support, du point de vue juridique, de la «déclaration du Gehad» par les dirigeants des divers secteurs des mouvements islamistes.

This review summarizes the findings and importance of 12 articles from research at Columbia University in New York City that were among the most cited in the literature between 2006 and 2011. The 12 articles summarized in this review made important contributions to the field of Alzheimer's disease in the last 5 years. Four of the articles established the Mediterranean diet as a food consumption pattern that may prevent Alzheimer's disease in addition to physical activity. Two of the articles advanced our knowledge of predictors of conversion from mild cognitive impairment to dementia. Four of the articles provided important knowledge of risk factors for the progression of Alzheimer's disease and its complications. Lastly, one of the articles laid the theoretical framework for the study of cognitive reserve, an important modifier of the manifestation of Alzheimer's disease. These studies have advanced our knowledge about risk factors, modifiers, and progression of late onset Alzheimer's disease

BACKGROUND: International travel plays a role in the spread of HIV-1 across Europe. It is, however, not known whether international travel is more important for spread of the epidemic as compared to endogenous infections within single countries. In this study, phylogenetic associations among HIV of newly diagnosed patients were determined across Europe. RESULTS: Data came from the SPREAD programme which collects samples of newly diagnosed patients that are representative for national HIV epidemics. 4260 pol sequences from 25 European countries and Israel collected in 2002-2007 were included.We identified 457 clusters including 1330 persons (31.2% of all patients). The cluster size ranged between 2 and 28. A number of 987 patients (74.2%) were part of a cluster that consisted only of patients originating from the same country. In addition, 135 patients (10.2%) were in a cluster including only individuals from neighboring countries. Finally, 208 patients (15.6%) clustered with individuals from countries without a common border. Clustering with patients from the same country was less prevalent in patients being infected with B subtype (P-value <0.0001), in men who have sex with men (P-value <0.0001), and in recently infected patients (P-value =0.045). CONCLUSIONS: Our findings indicate that the transmission of HIV-1 in Europe is predominantly occurring between patients from the same country. This could have implications for HIV-1 transmission prevention programmes. Because infections through travelling between countries is not frequently observed it is important to have good surveillance of the national HIV-1 epidemics.

The major risk factor of perinatal transmission of Hepatitis B virus (HBV) infection is the level of maternal HBV-deoxyribonucleic acid (DNA) during the third trimester of pregnancy. The primary aim of this study was to evaluate the hematological and biochemical status in Hepatitis B e-antigen (HBeAg)-negative chronic HBV-infected pregnant women and to correlate the findings with the presence or absence of viremia. Ninety-five consecutive chronic HBV-infected pregnant women were evaluated between the 28th and 32nd week of gestation. Viral load was determined by using the COBAS TaqMan HBV test. Sixty-nine women were evaluated and 14 of them exhibited HBV-DNA levels higher than 2000 IU·ml. In this study, viremic women exhibited significantly higher alanine aminotransferase (ALT), creatinine, and uric acid values as well as significantly lower white blood cell count compared with nonviremic women. There was also a significant statistical difference concerning ALT/sodium ratio between viremic and nonviremic women (0.20 ± 0.22 vs. 0.10 ± 0.09, respectively, p= .024). The optimal cutoff points discriminating those women with a high probability to have detectable serum HBV-DNA were 0.092 for ALT/sodium ratio (sensitivity = 73.0%, specificity = 61.5%, area under the receiver operating characteristic curve [AUC] = 71.05%) and 12.8 IU/L for ALT (sensitivity = 73.0%, specificity = 63.0%, AUC = 72.2%). Chronic HBV-infected pregnant women with ALT/sodium ratio ≥ 0.11 had the higher probability of having serum HBV-DNA levels higher than 2000 IU/ml (sensitivity = 76.92%, specificity = 58%, AUC = 62.38%). Presence of HBV-DNA in maternal blood during the third trimester of pregnancy is significantly associated with maternal serum ALT levels in HBeAg-negative chronic HBV-infected pregnant women. Women with an ALT/sodium ratio greater than 0.092 have the higher probability of HBV-DNA presence in maternal blood whereas an ALT/sodium ratio greater than 0.11 could discriminate those women with HBV-DNA levels higher than 2000 IU/ml.

The influence of microscale and mesoscale meteorology on the local scale variation of air temperature cannot be correctly simulated by the coarse resolution Global Climate Models. The scope of this work is to develop a hybrid dynamic-statistical downscaling procedure and quantify its predictive ability to estimate air temperature variability at finer spatial scales. The study focuses on the warm period of the year (June - August) and the method is applied to eight sites located in Greece with different topographical characteristics. The two-step methodology initially involves the dynamic downscaling of coarse resolution climate data via the RegCM4 regional climate model and subsequently the statistical downscaling of the modeled outputs by training site-specific artificial neural networks (ANN). The RegCM4 model is employed to enhance the representativity of the dataset, while the ANNs are used as function approximators to model the relationship between a number of atmospheric predictor variables and the observed air temperature time series. An insight of the ANN transfer function is obtained by examining the relative contribution of each input variable. The performance of the methodology is evaluated and the results indicate significant improvement from the inclusion of the ANN models in downscaling air temperature. © 2013 Global NEST Printed in Greece. All rights reserved.

OBJECTIVES: To examine in an observational study (1) relationships between cholinesterase inhibitors (ChEI) and memantine use, and functional and cognitive end points and mortality in patients with Alzheimer's disease (AD); (2) relationships between other patient characteristics and these clinical end points; and (3) whether effects of the predictors change across time. METHODS: The authors conducted a multicenter, natural history study that included three university-based AD centers in the United States. A total of 201 patients diagnosed with probable AD with modified Mini-Mental State Examination (MMSE) scores ≥ 30 at study entry were monitored annually for 6 years. Discrete-time hazard analyses were used to examine relationships between ChEI and memantine use during the previous 6 months reported at each assessment, and time to cognitive (MMSE score ≤ 10) and functional (Blessed Dementia Rating Scale score ≥ 10) end points and mortality. Analyses controlled for clinical characteristics, including baseline cognition, function, and comorbid conditions, and presence of extrapyramidal signs and psychiatric symptoms at each assessment interval. Demographic characteristics included baseline age, sex, education, and living arrangement at each assessment interval. RESULTS: ChEI use was associated with delayed time in reaching the functional end point and death. Memantine use was associated with delayed time to death. Different patient characteristics were associated with different clinical end points. CONCLUSIONS: Results suggest long-term beneficial effects of ChEI and memantine use on patient outcomes. As for all observational cohort studies, observed relationships should not be interpreted as causal effects.

Laboratory-size dye solar cells (DSCs), based on industrially feasible materials and processes employing liquid electrolytes, have been developed. Cells based on two electrolyte solvents with different physical properties were subjected to thermal stress test at 80 C for 2000 h in the dark to monitor their long-term thermal stability. The DSCs incorporating a methoxypropionitrile (MPN)-based electrolyte presented a severe efficiency loss at 1 sun AM 1.5G of more than 70% upon thermal aging, while the solar cells using tetraglyme (TG) as a high boiling point solvent attained a promising stability with only 20% loss of performance. To better understand the above behavior, systematic experiments, including optical microscopy, linear sweep voltammetry, UV-vis absorption, electrochemical impedance, and Raman spectroscopies were conducted. Virtually no dye degradation/desorption, electrolyte decomposition, semiconductor passivation, or loss of cathode activity could be identified. For the MPN-based cells, a sharp decrease in the short-circuit photocurrent was observed at high illumination intensities following thermal stress, attributed to charge-transfer limitations due to severe triiodide loss, verified by different experimental techniques. These degradation effects were efficiently mitigated by replacing MPN with the high-boiling-point solvent in the electrolyte. © 2013 American Chemical Society.

BACKGROUND: Prostate cancer (PCa) is characterised by great heterogeneity of the disease progression rate. Tumours range from insignificant and not life threatening to high risk for relapse ones. Consequently, a large number of patients undergo unnecessary treatment. miR-145 is a well-documented tumour suppressor and its expression, which is regulated by the p53 pathway, has been found to be decreased in the majority of human malignancies. The aim of our study was to evaluate the clinical utility of miR-145 for the prognostication of PCa. METHODS: Total RNA was isolated from 137 prostate tissue specimens obtained from 73 radical prostatectomy-treated PCa patients and 64 transurethral- or open prostatectomy-treated benign prostate hyperplasia (BPH) patients. Following polyadenylation and reverse transcription, miR-145 levels were determined by quantitative real-time PCR assay, using SNORD48 (RNU48) for normalisation purposes. RESULTS: Downregulated miR-145 expression was found in PCa compared with BPH patients. The reduction of miR-145 expression in PCa was correlated with higher Gleason score, advanced clinical stage, larger tumour diameter and higher prostate-specific antigen (PSA) and follow-up PSA levels. In addition, higher risk for biochemical recurrence and significantly shorter disease-free survival (DFS) was found for the PCa patients expressing lower miR-145. Focusing on 'low- and intermediate-recurrence risk' PCa patients, miR-145 loss was revealed to be a reliable predictor of biochemical relapse and poor DFS independent from Gleason score, clinical stage, PSA and patients' age. CONCLUSION: The loss of the tumour-suppressor miR-145 increases the risk for disease progression and predicts the poor survival of PCa patients.

Introduction and hypothesis: Congenital vaginal aplasia is a condition with devastating implications for fertility and sexuality. However, little is known on whether urinary symptomatology is more common prior and following vaginal lengthening procedures in these women. Methods: We performed a prospective observational study of 19 women with vaginal agenesis before and after vaginal dilation treatment or a laparoscopic Vecchietti procedure. All women completed the ICIQ FLUTS questionnaire before and after treatment in order to assess incidence and changes in urinary symptomatology. Results: Urinary symptoms were present in 53{%} of women prior to treatment. The majority of bladder symptoms were not significantly altered by treatment, except for incomplete bladder emptying. Women following the Vecchietti procedure had increased urinary hesitancy and a poorer steam compared with those completing dilation treatment. The longer the vaginal length, the greater the urinary frequency. Conclusion: Women with vaginal agenesis had significant levels of urinary symptoms and to our knowledge this has not been reported before. The majority of symptoms were not altered by treatment. © 2012 The International Urogynecological Association.

Malassezia yeasts are commensal microorganisms, which under insufficiently understood conditions can become pathogenic. We have previously shown that specific strains isolated from diseased human skin can preferentially produce agonists of the aryl hydrocarbon receptor (AhR), whose activation has been linked to certain skin diseases. Investigation of skin scale extracts from patients with Malassezia-associated diseases demonstrated 10-to 1,000-fold higher AhR-activating capacity than control skin extracts. Liquid chromatography-tandem mass spectrometry analysis of the patients’ extracts revealed the presence of indirubin, 6-formylindolo[3,2-b]carbazole (FICZ), indolo[3,2-b]carbazole (ICZ), malassezin, and pityriacitrin. The same compounds were also identified in 9 out of 12 Malassezia species culture extracts tested, connecting their presence in skin scales with this yeast. Studying the activity of the Malassezia culture extracts and pure metabolites in HaCaT cells by reverse transcriptase real-time PCR revealed significant alterations in mRNA levels of the endogenous AhR-responsive genes Cyp1A1, Cyp1B1, and AhRR. Indirubin-and FICZ-activated AhR in HaCaT and human HepG2 cells with significantly higher, yet transient, potency as compared with the prototypical AhR ligand, dioxin. In loco synthesis of these highly potent AhR inducers by Malassezia yeasts could have a significant impact on skin homeostatic mechanisms and disease development. © 2013 The Society for Investigative Dermatology.

Kriging interpolation technique is adapted to create the mapping of surface ozone seasonality and trends across Europe during 1997-2006, based on European Monitoring and Evaluation Programme ground measurements. The climatology, the annual and seasonal trends and the altitude above sea level (asl) dependence were studied as well as the relation with the North Atlantic Oscillation (NAO). The mean seasonal cycle amplitude and seasonal maximum display an increasing gradient from northwest to southeast, with high levels in Austria and eastern Mediterranean. Significantly close to 0 positive trends appear in UK, Slovakia, southern Scandinavia and Austria in winter and autumn. In Northern Hemisphere winter (December-February), about 40 % of near-surface ozone variability in the western edge of Europe may be attributed to circulation changes and ozone precursors' transport related to NAO. © 2013 Springer Science+Business Media Dordrecht.

INTRODUCTION: Our objective was to investigate potential associations between maxillary sinus floor extension and inclination of maxillary second premolars and second molars in patients with Class II Division 1 malocclusion whose orthodontic treatment included maxillary first molar extractions. METHODS: The records of 37 patients (18 boys, 19 girls; mean age, 13.2 years; SD, 1.62 years) treated between 1998 and 2004 by 1 orthodontist with full Begg appliances were used in this study. Inclusion criteria were white patients with Class II Division 1 malocclusion, sagittal overjet of ≥4 mm, treatment plan including extraction of the maxillary first permanent molars, no missing teeth, and no agenesis. Maxillary posterior tooth inclination and lower maxillary sinus area in relation to the palatal plane were measured on lateral cephalograms at 3 time points: at the start and end of treatment, and on average 2.5 years posttreatment. Data were analyzed for the second premolar and second molar inclinations by using mixed linear models. RESULTS: The analysis showed that the second molar inclination angle decreased by 7° after orthodontic treatment, compared with pretreatment values, and by 11.5° at the latest follow-up, compared with pretreatment. There was evidence that maxillary sinus volume was negatively correlated with second molar inclination angle; the greater the volume, the smaller the inclination angle. For premolars, inclination increased by 15.4° after orthodontic treatment compared with pretreatment, and by 8.1° at the latest follow-up compared with baseline. The volume of the maxillary sinus was not associated with premolar inclination. CONCLUSIONS: We found evidence of an association between maxillary second molar inclination and surface area of the lower sinus in patients treated with maxillary first molar extractions. Clinicians who undertake such an extraction scheme in Class II patients should be aware of this potential association and consider appropriate biomechanics to control root uprighting.

A hindcast simulation in the Aegean–Levantine basins for the years 1960–2000 is performed, using an eddy resolving ocean model (1°/30). The model incorporates a 6-h atmospheric forcing provided by the ARPERA and captures the observed variability of the 40-years. The Eastern Mediterranean Transient (EMT) is the most prominent climatic event of the period. We investigate the impact of the atmospheric versus lateral forcing on the buoyancy content of the Aegean–Levantine basins. During the pre-EMT period, the basins’ buoyancy content is lowered by surface fluxes by about 1.5×10−8m2s−3 in the Aegean Sea, mostly related to surface heat loss, and lateral fluxes by about 0.9×10−8m2s−3, mostly related to salt flux, with the Levantine changes leading those of the Aegean. Furthermore, while long-term trends of surface and lateral inputs are preconditioning the changes in the Aegean stratification, it is the extreme heat loss pulses, related to the variability of the wind field that is controlling the formation processes by abruptly lowering the buoyancy content. Those events are possibly linked to an eastern Mediterranean bimodal atmospheric oscillation, with the anomalous surface heat fluxes shifting from the Levantine in the 1960s to the Aegean in the 1990s. The central Aegean due to its topography and thermohaline properties trigger events of excessive formation and producing the Aegean’s densest waters. During the EMT winters the central Aegean lower layers contain very dense waters, with σΘ larger than 29.3kgm−3. These waters form the core of the water mass outflowing in the Eastern Mediterranean, after being mixed with ambient waters along their southward flow. The outflowing layer is characterized by density of 29.21kgm−3. The deepest parts of the NW Levantine is initially filled with the new water mass, which later spreads to the SE parts of the basin, flowing over the Eastern Mediterranean Ridge.

OBJECTIVE: This meta-analysis aims to quantitatively synthesize all studies that examine the association between adherence to a Mediterranean diet and risk of stroke, depression, cognitive impairment, and Parkinson disease. METHODS: Potentially eligible publications were those providing effect estimates of relative risk (RR) for the association between Mediterranean diet and the aforementioned outcomes. Studies were sought in PubMed up to October 31, 2012. Maximally adjusted effect estimates were extracted; separate analyses were performed for high and moderate adherence. RESULTS: Twenty-two eligible studies were included (11 covered stroke, 9 covered depression, and 8 covered cognitive impairment; only 1 pertained to Parkinson's disease). High adherence to Mediterranean diet was consistently associated with reduced risk for stroke (RR = 0.71, 95% confidence interval [CI] = 0.57-0.89), depression (RR = 0.68, 95% CI = 0.54-0.86), and cognitive impairment (RR = 0.60, 95% CI = 0.43-0.83). Moderate adherence was similarly associated with reduced risk for depression and cognitive impairment, whereas the protective trend concerning stroke was only marginal. Subgroup analyses highlighted the protective actions of high adherence in terms of reduced risk for ischemic stroke, mild cognitive impairment, dementia, and particularly Alzheimer disease. Meta-regression analysis indicated that the protective effects of Mediterranean diet in stroke prevention seemed more sizeable among males. Concerning depression, the protective effects of high adherence seemed independent of age, whereas the favorable actions of moderate adherence seemed to fade away with more advanced age. INTERPRETATION: Adherence to a Mediterranean diet may contribute to the prevention of a series of brain diseases; this may be of special value given the aging of Western societies.

Accumulating evidence supports that psoriasis may be a potential multisystem inflammatory disease associated with a range of co-morbidities showing an overlapping pathology and an important health impact such as metabolic diseases.   Psoriasis is associated with an increased risk of obesity, metabolic syndrome (Mets) and diabetes mellitus type 2 (t2DM), following a “dose-response” relationship from mild to severe psoriasis. Conversely, recent evidence from large prospective studies suggests that obesity constitutes a risk factor for psoriasis and psoriatic arthritis. Also, a dyslipidemic profile may precede psoriasis onset. Both obesity, Mets and psoriasis, characterized as chronic inflammatory states, stem from a shared underlying pathophysiology exhibiting common genetic predisposition and risk factors such as high caloric intake, physical inactivity and psychological stress. Excess weight may potentiate the inflammation of psoriasis through the deregulation of adipocytokines while, at the same time, it may help the development of Mets. Interestingly, recent translational data has shown that psoriasis, through increased T-helper inflammatory cytokines in skin and sera, may exert a plethora of effects on insulin regulation and lipid metabolism. Larger population-based prospective cohort and longitudinal studies are needed to unravel the association between psoriasis and metabolic co-morbidities. The recognition of the intricate complex interplay between psoriasis and metabolic co-morbidities may help dermatologists to be aware of associated metabolic co-morbidities in order to screen for metabolic diseases and manage holistically and effectively the psoriatic patient.

Medullary thyroid carcinoma (MTC) is a rare tumour which frequently occurs in the context of the multiple endocrine neoplasia syndromes, where it coexists with other usually benign tumours. The clinical picture varies and distant metastases are frequently present at diagnosis. Calcitonin levels are elevated in the presence of metastatic disease. Two MTC cases are presented, which had elevated postoperative calcitonin levels. Imaging revealed lung lesions which were originally attributed to metastatic disease from the MTC. However, at follow-up, these cases presented unusual features. The rapid increase in the lung lesions and the development of hypercalcaemia in the first patient suggested a second unrelated tumour. Biopsy of the lung lesion was compatible with lung adenocarcinoma. In the second patient, the appearance of a liver mass, although calcitonin levels remained stable, led to biopsy of the lesion: this was negative for calcitonin and compatible with metastatic lung adenocarcinoma. These MTC cases show that further malignancies may coexist with MTC and may obscure the clinical picture and influence the therapeutic decisions, especially in the case of metastatic disease. Features such as unusual imaging characteristics and the development of hypercalcemia, never encountered in MTC outside the MEN2 syndromes, as well as 'disproportionately' low calcitonin levels, incompatible with extensive metastatic disease, were the factors that led to further work-up. Both the cases subsequently proved to carry an unsuspected second malignancy. It is crucial to discriminate the metastatic lesion attributed to MTC from another coexisting primary malignancy, because different therapeutic strategies are needed for each setting. © 2013 Springer Science+Business Media New York.

Integrating amplifying media with metamaterials allows loss-free plasmonic operation and opens a route for controlling nanoscale quantum emitters.

The Aegean region of Greece hosts a series of crustal-scale extensional detachment systems that have accommodated the southward retreating Hellenic subduction zone. Extension has overprinted and dissected the Alpine nappe pile and locally exhumed Cordilleran-type metamorphic core complexes. On the island of Paros, a low-angle extensional detachment fault separates metamorphic footwall rocks from an unmetamorphosed sedimentary succession of the hanging wall. Basement orthogneisses were extensionally sheared in the footwall of the detachment until after 16. Ma (zircon U-Pb age of a slightly deformed granite), but pervasive ductile deformation had ceased by 7. Ma (zircon U-Pb age of an undeformed rhyolite dike that intrudes gneisses). Apatite and zircon (U-Th)/He ages from the gneisses confirm a period of cooling at rates >. 100. °C/Ma from 16 to 7. Ma. In the upper-plate, the basal sedimentary unit yields reset detrital apatite (U-Th)/He (DAHe) ages from 17 to 7. Ma and detrital zircon (U-Th)/He (DZHe) ages ranging from 270 to 18. Ma. DAHe ages from the stratigraphically higher fanglomerate units are reset to 10-7. Ma. The DZHe data have a primary thermal signature of 12-7. Ma, but preserve ages up to 113. Ma. The uppermost conglomerates exhibit completely reset DAHe ages of 15-9. Ma and reset DZHe ages from 10 to 8. Ma, with DZHe ages up to 104. Ma. Reset DAHe ages indicate late exposure of the footwall and constrain the depositional age of most sedimentary rocks on Paros to be from 14 to 7. Ma. Unreset DZHe ages preserve thermal signatures from the major Mesozoic-Tertiary tectonic events in the Aegean Region: [1] Cretaceous Pelagonian-type metamorphism; [2] Eocene peak HP metamorphism; and [3] Miocene Barrovian overprinting. Preservation of these signatures indicates long-term upper-plate recycling prior to syn-extensional deposition. The Paros supradetachment basin represents a classic inverted unroofing sequence deposited during progressive core complex exhumation in the Middle to Late Miocene. © 2012 Elsevier B.V.

This case control study aims to investigate the role of MMP-2 -1306C > T polymorphism as a potential risk factor and possible prognostic marker for breast cancer in a South European population. 113 consecutive incident cases of histologically confirmed ductal breast cancer and 124 healthy controls were recruited. MMP-2 -1306C > T polymorphism was genotyped; multivariate logistic regression as well as Cox regression analysis were performed. MMP-2 -1306C > T status was not associated with breast cancer risk either at the total sample or at the subanalyses on premenopausal and postmenopausal women. At the survival analysis, a trend towards a favorable association between MMP-2 -1306C > T allele and disease-free survival as well as overall survival was observed. Regarding subanalyses on ER-negative and ER-positive cases, the favorable association implicating MMP-2 -1306C > T allele was particularly evident among ER-positive cases; no significant associations emerged among ER-negative cases. MMP-2 -1306C > T polymorphism does not seem to be a risk factor for breast cancer in South European population; however, a trend towards a favorable association with survival has been observed. © 2013 Springer Science+Business Media Dordrecht.

In many cases, technological advances are based on artificial low-dimensional structures of heterogeneous constituents, thus called hybrids, that when come together they provide stand-alone entities that exhibit entirely different properties. Such hybrids are nowadays intensively studied since they are attractive for both basic research and oncoming practical applications. Here, we studied hybrids constituted of piezoelectric (PE) and ferromagnetic (FM) components in the form FM/PE/FM, ultimately aiming to provide means for the controlled modulation of the properties of the FM electrodes, originating from the strain imposed to them by the PE mediator when an electric field is applied. The PE component is in single crystal form, 0.71Pb(Mg1/3Nb2/3)O-3-0.29PbTiO(3) (PMN-PT), while the FM outer layers are Cobalt (Co) in thin film form. Detailed magnetization measurements performed under variation of the electric field applied to PMN-PT demonstrated the efficient modulation of the properties of the Co electrodes at low temperature (coercive field modulation up to 27% and saturation magnetization absolute modulation up to 4% at T = 10K for electric field not exceeding 6 kV/cm). The modulation degree faints upon increase of the temperature, evidencing that the thermal energy eventually dominates all other relevant energy scales. Candidate mechanisms are discussed for the explanation of these experimental observations. The results presented here demonstrate that commercially available materials can result in quantitatively noticeable effects. Thus, such elemental Co/PMN-PT/Co units can be used as a solid basis for the development of devices. (C) 2013 AIP Publishing LLC.

Here we examine the carbapenem and metronidazole resistance mechanisms of 640 Bacteroides strains reported in the 2008-2009 European antibiotic susceptibility survey. Of the 22 strains with elevated imipenem minimum inhibitory concentrations (≥4 μg/mL), 10 were cfiA-positive and out of these 5 carried activating insertion sequence (IS) elements in the upstream regions of the cfiA genes. However, resistant strains with cfiA genes but with no activating IS elements were found (n=2) as well as a resistant strain with no cfiA gene. In the former the resistance phenotypes by Etest were heterogeneous, whilst in the latter no carbapenemase production was seen; both mechanisms have been rarely observed, examined and characterised. Interestingly, few (n=3) nim-positive strains were found, including one metronidazole-resistant strain harbouring nimE activated by ISBf6, and two susceptible strains harbouring chromosomally located nim genes.

Correct identification of the culprit allergen is an essential part of diagnosis and treatment in immunoglobulin E (IgE)-mediated allergic diseases. In recent years, molecular biology has made important advances facilitating such identification and overcoming some of the drawbacks of natural allergen extracts, which consist of mixtures of various proteins that may be allergenic or not, specific for the allergen source or widely distributed (panallergens). New technologies offer the opportunity for a more accurate component-resolved diagnosis, of benefit especially to polysensitized allergic patients. The basic elements of molecular diagnostics with potential relevance to immunotherapy prescription are reviewed here, with a focus on Southern European sensitization patterns to pollen allergens. We propose a basic algorithm regarding component-resolved diagnostic work-up for pollen allergen-specific immunotherapy candidates in Southern Europe; this and similar algorithms can form the basis of improved patient management, conceptually a 'Component-Resolved Allergy Management'.

Pancreatic cancer is the fourth leading cause of cancer-related death. Most patients present with an advanced stage of disease that has a dismal outcome, with a median survival of approximately 6 months. Evidently, there is a clear need for the development of new agents with novel mechanisms of action in this disease. A number of biological agents modulating different signal transduction pathways are currently in clinical development, inhibiting angiogenesis and targeting epidermal growth factor receptor, cell cycle, matrix metalloproteinases, cyclooxygenase-2, mammalian target of rapamycin, or proteasome. This is the first systematic review of the literature to synthesize all available data coming from trials and evaluate the efficacy and safety of molecular targeted drugs in unresectable and metastatic pancreatic cancer. However, it should be stressed that although multiple agents have been tested, only 9 phase 3 trials have been conducted and one agent (erlotinib) has been approved by the Food and Drug Administration for use in clinical practice. As knowledge accumulates on the molecular mechanisms underlying carcinogenesis in the pancreas, the anticipated development and assessment of molecularly targeted agents may offer a promising perspective for a disease which, to date, remains incurable. Copyright © 2013 by Lippincott Williams & Wilkins.

We investigate the origin of high-energy emission in blazars within the context of the leptohadronic one-zone model. We find that γ-ray emission can be attributed to synchrotron radiation either from protons or from secondary leptons produced via photohadronic processes. These possibilities imply differences not only in the spectral energy distribution (SED) but also in the variability signatures, especially in the X- and γ-ray regime. Thus, the temporal behaviour of each leptohadronic scenario can be used to probe the particle population responsible for the high-energy emission as it can give extra information not available by spectral fits. In this work, we apply these ideas to the non-thermal emission of Mrk 421, which is one of the best monitored TeV blazars. We focus on the observations of 2001 March, since during that period Mrk 421 showed multiple flares that have been observed in detail both in X-rays and γ-rays. First, we obtain pre-flaring fits to the SED using the different types of leptohadronic scenarios. Then, we introduce random-walk-type, small-amplitude variations on the injection compactness or on the maximum energy of radiating particles and follow the subsequent response of the radiated photon spectrum. For each leptohadronic scenario, we calculate the X-ray and γ-ray fluxes and investigate their possible correlation. Whenever the `input' variations lead, apart from flux variability, also to spectral variability, we present the resulting relations between the spectral index and the flux, both in X-rays and γ-rays. We find that proton synchrotron models are favoured energetically but require fine tuning between electron and proton parameters to reproduce the observed quadratic behaviour between X-rays and TeV γ-rays. On the other hand, models based on pion decay can reproduce this behaviour in a much more natural way.

We investigate the origin of high-energy emission in blazars within the context of the leptohadronic one-zone model. We find that γ-ray emission can be attributed to synchrotron radiation either from protons or from secondary leptons produced via photohadronic processes. These possibilities imply differences not only in the spectral energy distribution (SED) but also in the variability signatures, especially in the X- and γ-ray regime. Thus, the temporal behaviour of each leptohadronic scenario can be used to probe the particle population responsible for the high-energy emission as it can give extra information not available by spectral fits. In this work, we apply these ideas to the non-thermal emission of Mrk 421, which is one of the best monitored TeV blazars. We focus on the observations of 2001 March, since during that period Mrk 421 showed multiple flares that have been observed in detail both in X-rays and γ-rays. First, we obtain pre-flaring fits to the SED using the different types of leptohadronic scenarios. Then, we introduce random-walk-type, small-amplitude variations on the injection compactness or on the maximum energy of radiating particles and follow the subsequent response of the radiated photon spectrum. For each leptohadronic scenario, we calculate the X-ray and γ-ray fluxes and investigate their possible correlation. Whenever the `input' variations lead, apart from flux variability, also to spectral variability, we present the resulting relations between the spectral index and the flux, both in X-rays and γ-rays. We find that proton synchrotron models are favoured energetically but require fine tuning between electron and proton parameters to reproduce the observed quadratic behaviour between X-rays and TeV γ-rays. On the other hand, models based on pion decay can reproduce this behaviour in a much more natural way.

Objective To assess the interaction of the MTHFR C677T polymorphism with changes in lipid and glucose metabolism effected by oral hormone replacement therapy (HRT) in postmenopausal women. Methods In this open-label, prospective, interventional study, parameters of lipid and glucose metabolism, as well as homocysteine, were assessed in 97 postmenopausal women at baseline and 1 year after the initiation of HRT. Participants were stratified into three subgroups, according to the MTHFR C677T polymorphism (wild-type: CC genotype; heterozygous: CT genotype; homozygous for the mutant variable: TT genotype). Results The TT genotype was associated with an elevation of total and low density lipoprotein (LDL) cholesterol, while CT and CC genotypes were associated with a reduction of total cholesterol and LDL cholesterol after 1 year of HRT (p = 0.032 for total cholesterol and p = 0.002 for LDL cholesterol). Women with the TT genotype had higher glucose levels in contrast to women with the CC genotype who had lower glucose levels after 1 year of HRT (p = 0.011). Additionally, CC carriers under HRT had a significant elevation of apolipoprotein A1 levels (p = 0.018), contrarily to CT and TT genotypes. Conclusion While HRT was associated with favorable changes in lipid and metabolic parameters in carriers of the CC genotype, this effect was not evident in carriers of the T allele. The MTHFR C677T polymorphism may modify the effect of HRT on lipid and metabolic parameters in postmenopausal women. © 2013 International Menopause Society.

A multiwalled carbon nanotube (MWCNT)-based electrochemical biosensor is developed for monitoring microcystin-LR (MC-LR), a toxic cyanobacterial toxin, in sources of drinking water supplies. The biosensor electrodes are fabricated using vertically well-aligned, dense, millimeter-long MWCNT arrays with a narrow size distribution, grown on patterned Si substrates by water-assisted chemical vapor deposition. High temperature thermal treatment (2500 °C) in an Ar atmosphere is used to enhance the crystallinity of the pristine materials, followed by electrochemical functionalization in alkaline solution to produce oxygen-containing functional groups on the MWCNT surface, thus providing the anchoring sites for linking molecules that allow the immobilization of MC-LR onto the MWCNT array electrodes. Addition of the monoclonal antibodies specific to MC-LR in the incubation solutions offers the required sensor specificity for toxin detection. The performance of the MWCNT array biosensor is evaluated using micro-Raman spectroscopy, including polarized Raman measurements, X-ray photoelectron spectroscopy, cyclic voltammetry, optical microscopy, and Faradaic electrochemical impedance spectroscopy. A linear dependence of the electron-transfer resistance on the MC-LR concentration is observed in the range of 0.05 to 20 μg L-1, which enables cyanotoxin monitoring well below the World Health Organization (WHO) provisional concentration limit of 1 μg L-1 for MC-LR in drinking water. An highly sensitive Faradaic electrochemical impedance biosensor for monitoring microcystin-LR (MC-LR) in sources of drinking water supplies is developed using millimeter-long multiwalled carbon nanotube (MWCNT) arrays grown by water-assisted chemical vapor deposition with vertical alignment. A linear sensing response shows a wide microcystin-LR concentration range that is below the World Health Organization (WHO) provisional guideline limit of 1 μg L-1 for MC-LR in drinking water. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

En este artículo se presentan la narración y la argumentación desde dos perspectivas:la lingüística y la cognitiva. Por un lado, nos detendremos en la narración y en laargumentación como tipos discursivos presentando las diferentes definiciones dadaspor los investigadores, así como los elementos característicos que las distinguen deotros tipos discursivos. Además, se exponen las diversas maneras en que las mismaspueden estar estructuradas. Por otro, las examinaremos desde la perspectiva cognitiva,es decir, como una modalidad de pensamiento y una habilidad cognitiva humana. Finprincipal del presente estudio es servir de herramienta didáctica a todos aquellosdocentes de LE que se vean involucrados en la enseñanza de los tipos textuales en laproducción escrita.

Neudesin (also known as neuron derived neurotrophic factor, Nenf) is a scarcely studied putative non-canonical neurotrophic factor. In order to understand its function in the brain, we performed an extensive behavioral characterization (motor, emotional, and cognitive dimensions) of neudesin-null mice. The absence of neudesin leads to an anxious-like behavior as assessed in the elevated plus maze (EPM), light/dark box (LDB) and novelty suppressed feeding (NSF) tests, but not in the acoustic startle (AS) test. This anxious phenotype is associated with reduced dopaminergic input and impoverished dendritic arborizations in the dentate gyrus granule neurons of the ventral hippocampus. Interestingly, shorter dendrites are also observed in the bed nucleus of the stria terminalis (BNST) of neudesin-null mice. These findings lead us to suggest that neudesin is a novel relevant player in the maintenance of the anxiety circuitry.

Neudesin (also known as neuron derived neurotrophic factor, Nenf) is a scarcely studied putative non-canonical neurotrophic factor. In order to understand its function in the brain, we performed an extensive behavioral characterization (motor, emotional, and cognitive dimensions) of neudesin-null mice. The absence of neudesin leads to an anxious-like behavior as assessed in the elevated plus maze (EPM), light/dark box (LDB) and novelty suppressed feeding (NSF) tests, but not in the acoustic startle (AS) test. This anxious phenotype is associated with reduced dopaminergic input and impoverished dendritic arborizations in the dentate gyrus granule neurons of the ventral hippocampus. Interestingly, shorter dendrites are also observed in the bed nucleus of the stria terminalis (BNST) of neudesin-null mice. These findings lead us to suggest that neudesin is a novel relevant player in the maintenance of the anxiety circuitry.

We report on integrated geomorphological, mineralogical, geochemical and biological investigations of the hydrothermal vent field located on the floor of the density-stratified acidic (pH   5) crater of the Kolumbo shallow-submarine arc-volcano, near Santorini. Kolumbo features rare geodynamic setting at convergent boundaries, where arc-volcanism and seafloor hydrothermal activity are occurring in thinned continental crust. Special focus is given to unique enrichments of polymetallic spires in Sb and Tl (±Hg, As, Au, Ag, Zn) indicating a new hybrid seafloor analogue of epithermal-to-volcanic-hosted-massive-sulphide deposits. Iron microbial-mat analyses reveal dominating ferrihydrite-type phases, and high-proportion of microbial sequences akin to "Nitrosopumilus maritimus", a mesophilic Thaumarchaeota strain capable of chemoautotrophic growth on hydrothermal ammonia and CO2. Our findings highlight that acidic shallow-submarine hydrothermal vents nourish marine ecosystems in which nitrifying Archaea are important and suggest ferrihydrite-type Fe3+-(hydrated)-oxyhydroxides in associated low-temperature iron mats are formed by anaerobic Fe2+-oxidation, dependent on microbially produced nitrate.

This paper concerns records of species that have extended their distribution in the Mediterranean Sea. The finding of the rare brackish angiosperm Althenia filiformis in the island of Cyprus is interesting since its insertion in the Red Data Book of the Flora of Cyprus is suggested. The following species enriched the flora or fauna lists of the relevant countries: the red alga Sebdenia dichotoma (Greece), the hydrachnid mite Pontarachna adriatica (Slovenia), and the thalassinid Gebiacantha talismani (Turkey). Several alien species were recorded in new Mediterranean localities. The record of the burrowing goby Trypauchen vagina in the North Levantine Sea (Turkish coast), suggests the start of spreading of this Lessepsian immigrant in the Mediterranean Sea. The findings of the following species indicate the extension of their occurrence in the Mediterranean Sea: the foraminifer Amphistegina lobifera (island of Zakynthos, Greece), the medusa Cassiopea andromeda (Syria), the copepod Centropages furcatus (Aegean Sea), the decapod shrimp Melicertus hathor (island of Kastellorizo, Greece), the crab Menoethius monoceros (Gulf of Tunis), the barnacles Balanus trigonus, Megabalanus tintinnabulum, Megabalanus coccopoma and the bivalves Chama asperella, Cucurbitula cymbium (Saronikos Gulf, Greece).

This paper concerns records of species that have extended their distribution in the Mediterranean Sea. The finding of the rare brackish angiosperm Althenia filiformis in the island of Cyprus is interesting since its insertion in the Red Data Book of the Flora of Cyprus is suggested. The following species enriched the flora or fauna lists of the relevant countries: the red alga Sebdenia dichotoma (Greece), the hydrachnid mite Pontarachna adriatica (Slovenia), and the thalassinid Gebiacantha talismani (Turkey). Several alien species were recorded in new Mediterranean localities. The record of the burrowing goby Trypauchen vagina in the North Levantine Sea (Turkish coast), suggests the start of spreading of this Lessepsian immigrant in the Mediterranean Sea. The findings of the following species indicate the extension of their occurrence in the Mediterranean Sea: the foraminifer Amphistegina lobifera (island of Zakynthos, Greece), the medusa Cassiopea andromeda (Syria), the copepod Centropages furcatus (Aegean Sea), the decapod shrimp Melicertus hathor (island of Kastellorizo, Greece), the crab Menoethius monoceros (Gulf of Tunis), the barnacles Balanus trigonus, Megabalanus tintinnabulum, Megabalanus coccopoma and the bivalves Chama asperella, Cucurbitula cymbium (Saronikos Gulf, Greece).

Several epidemiological studies have shown that the traditional Mediterranean diet is associated with a lower incidence of atherosclerosis, cardiovascular disease, neurodegenerative diseases, and certain kinds of cancer. These appreciable health-promoting properties have been partially correlated with the regular consumption of extra virgin olive oil as the principal source of fat. Olive oil is the most famous agricultural product in the Mediterranean, with a history as old as that region’s civilization. Olive fruits and olive oil not only are delicious but also have been considered as medicines since ancient times.

Group VIA calcium-independent phospholipase A2 (GVIA iPLA2) has recently emerged as an important pharmaceutical target. Selective and potent GVIA iPLA2 inhibitors can be used to study its role in various neurological disorders. In the current work, we explore the significance of the introduction of a substituent in previously reported potent GVIA iPLA2 inhibitors. 1,1,1,2,2-Pentafluoro-7-(4-methoxyphenyl)heptan-3-one (GK187) is the most potent and selective GVIA iPLA2 inhibitor ever reported with a XI(50) value of 0.0001, and with no significant inhibition against GIVA cPLA2 or GV sPLA2. We also compare the inhibition of two difluoromethyl ketones on GVIA iPLA2, GIVA cPLA2, and GV sPLA2.

In a monitoring observation of the central region of the Andromeda Galaxy (M 31) with the Ultra-violet/Optical Telescope (UVOT) on board the Swift satellite (ObsID 00035336102, starting 2013-05-27.15 UT), we detected a new UV transient (UVW1 filter, 181-321 nm). The source is located at RA 00h 42m 55.62s, Dec +41d 14' 12.3" (± 0.5", J2000, 90% confidence level). The following table lists the Swift ObsID, the MJD at the beginning of the exposure, UVW1 magnitudes (Vega system), and 1σ statistical uncertainties.

In the early 80s, the word automation was used in the clinical laboratory setting referring only to analyzers. But in late 80s and afterwards, automation found its way into all aspects of the diagnostic process, embracing not only the analytical but also the pre- and post-analytical phase. While laboratories in the eastern world, mainly Japan, paved the way for laboratory automation, US and European laboratories soon realized the benefits and were quick to follow. Clearly, automation and robotics will be a key survival tool in a very competitive and cost-concious healthcare market. What sets automation technology apart from so many other efficiency solutions are the dramatic savings that it brings to the clinical laboratory. Further standardization will assure the success of this revolutionary new technology. One of the main difficulties laboratory managers and personnel must deal with when studying solutions to reengineer a laboratory is familiarizing themselves with the multidisciplinary and technical terminology of this new and exciting field. The present review/glossary aims at giving an overview of the most frequently used terms within the scope of laboratory automation and to put laboratory automation on a sounder linguistic basis.

A detailed and rigorous theoretical investigation of the optical properties of a generic three-dimensional chiral structure of plasma spheres, without and under the action of an external static uniform magnetic field, is presented. Corresponding photonic band diagrams in conjunction with relevant transmission spectra, calculated by the full electrodynamic layer-multiple-scattering method properly extended to the case of gyrotropic spherical scatterers, are discussed in the light of the theory of nonsymmorphic space groups. This analysis provides a consistent interpretation of some remarkable features and effects like Dirac points, polarization-dependent transmission, as well as band splitting and non-reciprocal optical response that emerge as a result of time-reversal-symmetry breaking, induced by the external static magnetic field, and the lack of space-inversion symmetry in the crystal.

We report on the occurrence and properties of photonic surface states in periodic structures of magnetized plasma nanospheres by means of rigorous calculations using the full-electrodynamic layer-multiple-scattering method, properly extended to treat gyrotropic spheres with arbitrarily oriented gyration vector. More specifically, dispersion diagrams of Tamm states at the (001) surface of a semi-infinite fcc crystal of plasma nanospheres and of guided modes of a square array of such spheres supported by a quartz substrate, without and under the action of an in-plane static uniform magnetic field, are analyzed and nonreciprocal optical response, which emerges as a result of the simultaneous lack of space-inversion and time-reversal symmetries, is demonstrated in the Voigt geometry.

When a healthy woman expresses concerns about her vulva, the doctor's response should be informed by clinical knowledge. For many doctors, accumulation of such knowledge would have begun with undergraduate teaching and medical textbooks. The aim of this study is to examine the information on female genital morphology in medical textbooks. A total of 59 gynaecology and anatomy textbooks were searched for information on the dimensions of vulval constitutent parts. No textbook gave measurements for all vulval structures. Vaginal length was reported in 21/59 textbooks, clitoral size in 15/59 and labia minora in 1/59. Where measurements appear, they suggest narrower ranges than recent reports. Information of vulval morphology is scanty and inaccurate in medical textbooks. The general lack of professional resources means that doctors may consciously or non-consciously rely upon personal experiences and popular culture to form their opinions, as do their patients. © 2013 Informa UK, Ltd.

Selected CCD photometry of the nova forwarded by E. Waagen, AAVSO: Aug. 13.955 UT, [10.2 (G. Murawski, Suwalki, Poland; V-band); 14.817, V = 6.5 (I. Sergey, Molodechno, Belarus); 14.872, V = 6.43 (P. Hallsten, Vasterhaninge, Sweden); 14.876, B = 6.43 (L. Corp, Rodez, France); 14.877, V = 6.11 (Corp); 14.878, R = 5.68 (Corp); 15.837, B = 5.35 (T. Wikander, Borlange, Sweden); 15.883, V = 5.13 (A. Sonka, Bucharest, Romania); 16.037, I = 4.60 (K. Gazeas, Athens, Greece); 16.035, R = 4.71 (Gazeas); 16.033, V = 4.80 (Gazeas); 16.031, B = 4.97 (Gazeas); 16.279, V = 4.44 (A. Oksanen, Muurame, Finland); 16.278, B = 4.82 (Oksanen);

DYRK kinases are involved in alternative pre-mRNA splicing as well as in neuropathological states such as Alzheimer’s disease and Down syndrome. In this study, we present the design, synthesis, and biological evaluation of indirubins as DYRK inhibitors with enhanced selectivity. Modifications of the bis-indole included polar or acidic functionalities at positions 5' and 6' and a bromine or a trifluoromethyl group at position 7, affording analogues that possess high activity and pronounced specificity. Compound 6i carrying a 5'-carboxylate moiety demonstrated the best inhibitory profile. A novel inverse binding mode, which forms the basis for the improved selectivity, was suggested by molecular modeling and confirmed by determining the crystal structure of DYRK2 in complex with 6i. Structure-activity relationships were further established, including a thermodynamic analysis of binding site water molecules, offering a structural explanation for the selective DYRK inhibition. © 2012 American Chemical Society.

Blending of chewing gums of different colours is used in the clinical setting, as a simple and reliable means for the assessment of chewing efficiency. However, the available software is difficult to use in an everyday clinical setting, and there is no possibility of automated classification of the patient's chewing ability in a graph, to facilitate visualisation of the results and to evaluate potential chewing difficulties. The aims of this study were to test the validity of ViewGum - a novel image analysis software for the evaluation of boli derived from a two-colour mixing ability test - and to establish a baseline graph for the representation of the masticatory efficiency in a healthy population. Image analysis demonstrated significant hue variation decrease as the number of chewing cycles increased, indicating a higher degree of colour mixture. Standard deviation of hue (SDHue) was significantly different between all chewing cycles. Regression of the log-transformed values of the medians of SDHue on the number of chewing cycles showed a high statistically significant correlation (r² = 0.94, P < 0.01). ViewGum eliminates drawbacks of previous two-colour chewing gum test methods by the simplicity of its application. The newly developed ViewGum software provides speed, ease of use and immediate extraction of clinically useful conclusions to the already established method of chewing efficiency evaluation and is a valid adjunct for the evaluation of masticatory efficiency with two-colour chewing gum.

Worldwide, breast cancer (BC) represents the most common type of non-skin human malignancy and the second leading cause of cancer-related deaths amid women in Western countries. Obesity and its metabolic complications have rapidly become major global health issues and are associated with increased risk for cancer, especially BC in postmenopausal women. Adipose tissue is considered as a genuine endocrine organ secreting a variety of bioactive adipokines, such as leptin, adiponectin, resistin and nicotinamide phosphoribosyl-transferase/visfatin. Recent evidence has indicated that the constellation of obesity, insulin resistance and adipokines is associated with the risk and prognosis of postmenopausal BC. Direct evidence is growing rapidly supporting the stimulating and/or inhibiting role of adipokines in the process of development and progression of BC. Adipokines could exert their effects on the normal and neoplastic mammary tissue by endocrine, paracrine and autocrine mechanisms. Recent studies support a role of adipokines as novel risk factors and potential diagnostic and prognostic biomarkers in BC. This editorial aims at providing important insights into the potential pathophysiological mechanisms linking adipokines to the etiopathogenesis of BC in the context of a dysfunctional adipose tissue and insulin resistance in obesity. A better understanding of these mechanisms may be important for the development of attractive preventive and therapeutic strategies against obesity-related breast malignancy.

To date, an obesity/asthma link is well defined in adults; however, the nature of such a link is obscure in children, partly due to Body Mass Index (BMI) limitations as a surrogate fat mass marker in childhood. We thus opted to investigate the association of adiposity with asthma in children of different ages, using several indices to assess fat mass.|Wheeze ever/in the last 12 months (current) and physician-diagnosed asthma were retrospectively reported via questionnaire by the parents of 3641 children, participating in two cross-sectional studies: 1626 children aged 2-5 (the Genesis Study) and 2015 children aged 9-13 (the Healthy Growth Study). Perinatal data were recorded from the children's medical records or reported by parents. Anthropometric measurements (i.e., BMI, waist/hip circumference, biceps/triceps/subscapular/suprailiac skinfold thickness) were conducted in both cohorts; bioelectric impedance analysis (BIA) was conducted only in preadolescent children.|In children aged 2-5, asthma was positively correlated with conicity index, waist/hip circumference, waist-to-height ratio, skinfold thickness, and skinfold-derived percentage fat mass (P < 0.05) but not BMI or BMI-defined overweight/obesity, after adjusting for several confounders. In children aged 9-13, asthma was positively associated with conicity index, waist circumference, waist-to-height ratio, skinfold thickness, skinfold-derived percentage fat mass, BIA-derived percentage fat mass, BMI, and BMI-defined overweight/obesity, following adjustment (P < 0.05). Current/ever wheeze was not consistently associated with fat mass in either population.|Fat mass is positively linked to asthma in both 2-5 and 9-13 age spans. However, the failure of BMI to correlate with preschool asthma suggests its potential inefficiency in asthma studies at this age range.

The present study, deals with the 24-hour prognosis of the outdoor biometeorological conditions in an urban monitoring site within the Greater Athens area, Greece. For this purpose, artificial neural networks (ANNs) modelling techniques are applied in order to predict the maximum and the minimum value of the physiologically equivalent temperature (PET) one day ahead as well as the persistence of the hours with extreme human biometeorological conditions. The findings of the analysis showed that extreme heat stress appears to be 10.0% of the examined hours within the warm period of the year, against extreme cold stress for 22.8% of the hours during the cold period of the year. Finally, human thermal comfort sensation accounts for 81.8% of the hours during the year. Concerning the PET prognosis, ANNs have a remarkable forecasting ability to predict the extreme daily PET values one day ahead, as well as the persistence of extreme conditions during the day, at a significant statistical level of P < 0.01. © 2013 K. P. Moustris et al.

This article studies the dynamic control of arrivals of multiple job classes in N-stage production systems with finite buffers and blocking after service. A model with multiple processing stages in series is formulated as a Markov decision process and a state definition from the queueing analysis literature is used to simplify the state-space description. This allows several fundamental admission control results from M/M/N and M/M/N/N queueing models as well as tandem models without blocking to be extended to tandem systems with blocking. Specifically, it is shown that the net benefit of admitting a job declines monotonically with the system congestion; thus the decision to admit any job class is based on threshold values of the number of jobs present in the system. Furthermore, conditions under which a job class is always or never admitted, regardless of the state, are derived. The interaction of blocking and admission control is explored by analyzing the effect of blocking on the optimal admission policy and profit. The article concludes with analyses of why extensions including loss and abandonment cannot sustain the monotonicity properties and two surrogate admission rules that may be used in practice but do not account for the blocking effect. © 2013 Taylor & Francis Group, LLC.

Chios mastic gum, the resin obtained as an exudate from the trunk and branches of Pistacia lentiscus L var. chia, is used extensively as a constituent of herbal drugs or functional foods. The oral absorption of its major constituents still remains unclear. In the context of identifying the features of mastic gum that are responsible for either therapeutic effects or effects of nutritional value, a methodology based on high-performance liquid chromatography (HPLC) coupled to tandem mass spectrometry (MS/MS) was developed and applied for the quantification of mastic gum triterpenic acids, 24Z-isomasticadienonic acid (IMNA), and 24Z-isomasticadienolic acid (IMLA) in mouse plasma. The specific compounds were selected based on their biological activity and potential against Helicobacter pylori. Concentrations were determined simultaneously in mouse plasma after oral administration of mastic gum or total mastic extract without polymer (TMEWP) in order to evaluate the role of the natural polymer, poly-β-myrcene, in the absorption process. Following TMEWP administration in mice, circulating IMNA and IMLA plasma levels were significantly higher (approximately 10-fold) in comparison to IMNA and IMLA plasma levels following total mastic gum administration (CMG), suggesting that the polymer plays a critical role in the absorption process. More specifically following TMEWP administration, Cmax plasma values were 3300 ± 859 ng/mL for IMNA and 163 ± 58 ng/mL for IMLA. In comparison, following CMG administration, Cmax plasma values were 329 ± 57 ng/mL for IMNA and 28 ± 8 ng/mL for IMLA.The methodological approaches presented in this study, along with the findings, offer valuable information on the availability of bioactive components following ingestion of mastic and facilitate the uses of mastic either as an ingredient of functional foods or as a herbal drug. © Georg Thieme Verlag KG.

Using density functional theory calculations, ultrathin films of SrVO3(d(1)) and SrCrO3(d(2)) on SrTiO3 substrates have been studied as possible multiferroics. Although both are metallic in the bulk limit, they are found to be insulating as a result of orbital ordering driven by lattice distortions at the ultrathin limit. While the distortions in SrVO3 have a first-order Jahn-Teller origin, those in SrCrO3 are ferroelectric in nature. This route to ferroelectricity results in polarizations comparable with conventional ferroelectrics.

In this work, we prepared oriented mesoporous thin films of silica on various solid substrates using the pluronic block copolymer P123 as a template. We attempted to insert guest iron oxide (FexOy) nanoparticles into these films by two different methods: (a) by co-precipitation-where iron precursors are introduced in the synthesis sol before deposition of the silica film-and subsequent oxide production during the film calcination step; (b) by preparing and calcining the silica films first then impregnating them with the iron precursor, obtaining the iron oxide nanoparticles by a second calcination step. We have examined the structural effects of the guest nanoparticles on the silica film structures using grazing incidence X-ray scattering (GISAXS), high-resolution transmission electron spectroscopy (HRTEM), spectroscopic ellipsometry, X-ray photoelectron spectroscopy (XPS), and Raman microscopy. Formation of nanoparticles by co-precipitation may induce substantial changes in the film structure leading, in our adopted process, to the appearance of lamellar ordering in the calcination stage. On the contrary, impregnation-based approaches perturb the film structures much more weakly, but are also less efficient in filling the pores with nanoparticles. © 2013 by the authors.

Background: Tumour-associated lymphocytes (TALs) present in effusions of ovarian cancer patients exhibit impaired activities, due to the immunosuppressive environment of the ascites. Means to enhance their cytotoxicity against autologous tumour cells are of clinical importance. The immunomodulator prothymosin alpha (proTα) increases the specific lysis of tumour cells by activated CD8+ T-lymphocytes and its immunoreactivity is exerted by the carboxy-terminal decapeptide, proTα(100-109). These two molecules were studied on TALs in vitro, and in SCID mice bearing human ovarian tumours. Methods: TALs and tumour cells were isolated from 41 ovarian cancer patients and co-cultured in the presence of proTα or proTα(100-109). The cytotoxicity of peptide-stimulated TALs was tested against autologous tumour cells and K562. Ex vivo peptide-stimulated TALs from three patients were adoptively transferred intraperitoneally in SCID mice, previously inoculated with each patient's autologous tumour cells. Results: ProTα and its immunoreactive peptide proTα(100-109), enhanced the cytotoxic activity of TALs against autologous tumour cells in vitro, but marginally affected the lysis of K562. The effect of proTα and proTα(100-109) was higher after 7-14 days of stimulation, whereas TAL cytotoxicity was significantly decreased after 21 days. Mice administered TALs, ex vivo activated with proTα or proTα(100-109) for 7 days, showed a relatively lower tumour increase rate and a prolongation of their survial, compared to controls. Conclusion: Our data demonstrate that, in the presence of tumour antigens, proTα and proTα(100-109) enhance the depressed cytotoxicity of TALs against autologous tumour cells in vitro and retard tumour growth in vivo. © 2013 Elsevier Ltd. All rights reserved.

BACKGROUND: SAHA syndrome is characterized by the tetrad: seborrhea, acne, hirsutism, and androgenetic alopecia. No previous study has examined the prevalence of glucose abnormalities in ovarian SAHA and explored whether it may be an independent risk factor for glucose abnormalities. OBJECTIVE: In a prospective controlled study, we investigated the spectrum of glucose abnormalities in ovarian SAHA and explored whether it is associated with a more insulin-resistant profile. METHODS: In all, 316 patients with a diagnosis of polycystic ovary syndrome (PCOS) (56 with SAHA) and 102 age-matched healthy women were examined and underwent a 2-hour oral glucose tolerance test. Serum glucose homeostasis parameters, hormones, and adipokines were determined. RESULTS: SAHA prevalence was 17.7% in patients with PCOS and predominance of the severe PCOS phenotype. Ovarian SAHA was independently associated with a more insulin-resistant profile (higher homeostatic model assessment of insulin resistance score, lower quantitative insulin sensitivity check index [QUICKI] and MATSUDA indices, and relative hypoadiponectinemia), and represented an independent risk factor for glucose abnormalities regardless of anthropometric features, age, and PCOS phenotype. LIMITATION: There was no performance of skin biopsies. CONCLUSION: The prompt recognition of SAHA syndrome in women with PCOS permits an earlier diagnosis and surveillance of metabolic abnormalities, especially in Mediterranean PCOS population exhibiting a lower prevalence of glucose abnormalities.

OBJECTIVE: To examine whether both OX40 and its ligand OX40L are expressed in idiopathic inflammatory myopathies and to investigate the types of inflammatory cells expressing OX40L. STUDY DESIGN: Immunohistochemistry was performed in limb muscle specimens from dermatomyositis, polymyositis and inclusion body myositis patients to analyze the expression of OX40 and its ligand OX40L. Double immunofluorescence labeling was performed to clarify the phenotype of inflammatory cells expressing OX40L. RESULTS: OX40 and OX40L expressing cells were observed in all subsets of inflammatory myopathies following a similar pattern of distribution mainly in the perimysium. In polymyositis and inclusion body myositis inflammatory cells expressing the receptors invaded non-necrotic muscle fibers. OX40L expression was also found in endothelial blood cells in all dermatomyositis and some polymyositis specimens. In all subsets of inflammatory myopathies OX40L was expressed by T cells (CD4+ and CD8+), macrophages (CD68+), B cells (CD20+) and myeloid dendritic cells (BDCA1+). Plasmacytoid dendritic cells (BDCA2+) expressing OX40L were found only in dermatomyositis and polymyositis. CONCLUSION: The simultaneous expression of both OX40 and its ligand OX40L in idiopathic inflammatory myopathies suggests that they might participate in disease pathogenesis. Expression of OX40L by different types of cells within the inflamed muscle implies that OX40-OX40L interaction may contribute in disease mechanisms through different pathways.

The results of a comparison between monthly mean ozone column variations calculated from the chemical transport model Oslo CTM2 and those derived from solar backscatter ultraviolet (SBUV) satellite observations are presented for the period 1998-2009. Monthly mean total ozone derived from improved model simulations were used to compute monthly zonal means over 10 latitude zones over the northern and southern hemispheres. Ozone column variations from Oslo CTM2 are highly correlated with SBUV retrievals at all latitude zones. Equatorial zonal winds at 30 hPa were used as index to study the impact of quasi-biennial oscillation (QBO) on ozone. Correlations between modeled ozone and the QBO were found to be the order of +0.8 in the tropics. The impact of QBO was most pronounced at equatorial latitudes with amplitudes of +4 to -4 %. Seasonal variations in surface ozone and tropospheric ozone column calculated by the model are also presented. © 2013 Springer Science+Business Media Dordrecht.

Rhinitis is a common problem in childhood and adolescence and impacts negatively on physical, social and psychological well-being. This position paper, prepared by the European Academy of Allergy and Clinical Immunology Taskforce on Rhinitis in Children, aims to provide evidence-based recommendations for the diagnosis and therapy of paediatric rhinitis. Rhinitis is characterized by at least two nasal symptoms: rhinorrhoea, blockage, sneezing or itching. It is classified as allergic rhinitis, infectious rhinitis and nonallergic, noninfectious rhinitis. Similar symptoms may occur with other conditions such as adenoidal hypertrophy, septal deviation and nasal polyps. Examination by anterior rhinoscopy and allergy tests may help to substantiate a diagnosis of allergic rhinitis. Avoidance of relevant allergens may be helpful for allergic rhinitis (AR). Oral and intranasal antihistamines and nasal corticosteroids are both appropriate for first-line AR treatment although the latter are more effective. Once-daily forms of corticosteroids are preferred given their improved safety profile. Potentially useful add-on therapies for AR include oral leukotriene receptor antagonists, short bursts of a nasal decongestant, saline douches and nasal anticholinergics. Allergen-specific immunotherapy is helpful in IgE-mediated AR and may prevent the progression of allergic disease. There are still a number of areas that need to be clarified in the management of rhinitis in children and adolescents.

The history of Mediterranean vegetation can be outlined using pollen grains contained in lacustrine, marine and other sediments. These sediments have recorded very important vegetation changes during recent geological times. For example, during the last 6 Ma (million years), the effects of different events acting at regional (e.g. the Messinian salinity crisis between 5.96 Ma and 5.33 Ma) and global (expansion of the Arctic ice at ca 2.6 Ma) scales produced a progressive decrease and final disappearance of tropical and subtropical taxa. However, prior to the start of the Quaternary the Mediterranean flora still included a consistent number of tropical and subtropical arboreal taxa accompanying deciduous and partly evergreen trees that have persisted until today. The most important features of the vegetation history of the Quaternary consist in the fact that vegetation adapted to climate changes due to changes in orbital cyclicity, alternating between glacial and interglacial periods. The more widespread vegetation types were steppe and grassland formations during the dry and cold glacial periods whereas either deciduous or evergreen forests were characteristic of interglacial periods. These cold-dry to warmhumid climate cycles became more and more intense towards the present. During the second half of the present interglacial, after the mid-Holocene, joint actions of increasing dryness, climate oscillations and human impact led to the present day Mediterranean plant landscape. It is however not clear how far the causation of this spread of evergreen taxa was climatic or human. One of the most exciting challenges is the prediction of the future course of Mediterranean vegetation. In this perspective a consistent help, not fully explored yet, can be found in aeropalynology, recording the pollen transported in the air. Together with modern surface samples, these data act as modern analogues. Though it probably does not represent the same past vegetational composition, the current pollen rain is the only basic reference on which our comparative approach can rely. Present trends are interpreted and future scenarios can be hypothesized just using a combination of aero- and archaeo-/palaeo-palynological approaches.

Populations of many countries are becoming increasingly overweight and obese, driven largely by excessive calorie intake and reduced physical activity; greater body mass is accompanied by epidemic levels of comorbid metabolic diseases. At the same time, individuals are living longer. The combination of aging and the increased prevalence of metabolic disease is associated with increases in aging-related comorbid diseases such as Alzheimer's disease, cerebrovascular dementia, and sarcopenia. Here, correlative and causal links between diseases of overnutrition and diseases of aging and cognition are explored.

High-power high-frequency gyrotrons are required for several applications, including plasma heating, current drive, and plasmas stabilization for controlled thermonuclear fusion. Despite the use of dumping dielectric material in these gyrotrons, parasitic oscillations often appear, which significantly affect their operation and efficiency. In this paper, we perform an extended parametric study on the effect of the beam-tunnel characteristics, i.e., the outer radius of the inner waveguide and the width of the grooves, as well as the lossy material properties and the beam-radial position on the dumping of these oscillations.

The strong epidemiologic and pathophysiologic link between allergic rhinitis (AR) and asthma has led to the concept of 'united airways disease' or 'respiratory allergy', implying that allergy, in its widest sense, underlies this clinical syndrome. Progression from AR to asthma is frequent and part of the 'atopic march'. Since pediatric immune responses are more adaptable and therefore may be more amenable to treatment, interventions at early childhood are characterized by a higher chance to affect the natural history of respiratory allergy. Although current treatments are quite effective in alleviating respiratory allergy symptoms, it has proven much more difficult to confirm any influence on the progression of the disease. Much more promising is the field of specific allergen immunotherapy, where current evidence, although not yet of ideal robustness, points towards a disease-modifying effect. In addition, newer or emerging, possibly more effective or more targeted interventions are promising in the preventive sense.

Purpose This final analysis of the phase III VISTA trial (Velcade As Initial Standard Therapy in Multiple Myeloma: Assessment With Melphalan and Prednisone) was conducted to determine whether the overall survival (OS) benefit with bortezomib-melphalan-prednisone (VMP) versus melphalanprednisone (MP) in patients with myeloma who were ineligible for transplantation was maintained after 5 years of follow-up and to explore the risk of second primary malignancies. Patients and Methods In all, 682 patients received up to nine 6-week cycles of VMP or MP and were then observed every 12 weeks or less. Data on second primary malignancies were collected by individual patient inquiries at all sites from 655 patients. Results After median follow-up of 60.1 months (range, 0 to 74 months), there was a 31% reduced risk of death with VMP versus MP (hazard ratio [HR], 0.695; P < .001; median OS 56.4 v 43.1 months). OS benefit with VMP was seen across prespecified patient subgroups (age ≥ 75 years, stage III myeloma, creatinine clearance < 60 mL/min). Sixty-three percent of VMP patients and 73% of MP patients had received subsequent therapy. Time to next therapy (median, 30.7 v 20.5 months; HR, 0.557; P < .001) was longer with VMP than with MP. Among patients who received subsequent therapies, survival from start of subsequent therapy was similar following VMP (median, 28.1 months) or MP (median, 26.8 months; HR, 0.914). Following VMP/MP, incidence proportions of hematologic malignancies (1%/1%) and solid tumors (5%/3%) and exposure-adjusted incidence rates (0.017/0.013 per patient-year) were similar and were consistent with background rates. Conclusion VMP resulted in a significant reduction in risk of death versus MP that was maintained after 5 years' follow-up and despite substantial use of novel-agent-based salvage therapies. There is no emerging safety signal for second primary malignancies following VMP. © 2012 by American Society of Clinical Oncology.

Pertuzumab is a monoclonal antibody that represents the first among a new class of agents known as human epidermal growth factor receptor (HER) dimerization inhibitors. This is the first systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to synthesize all available data of pertuzumab in breast cancer. The search strategy retrieved 11 studies that evaluated pertuzumab. One study was conducted in the neoadjuvant setting (417 patients), whereas all the others dealt with patients with recurrent, metastatic, or refractory disease (1023 patients). Six studies were conducted in HER2+ breast cancer population (1354 patients), whereas 5 studies (86 patients) were conducted in HER2- (or unknown HER2 status) disease. Pertuzumab is the most recent agent approved by the US Food and Drug Administration in combination with trastuzumab and docetaxel for the treatment of patients with HER2+ metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. This approval has been based on data from a phase III Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) study. The antitumor activity with the significant reduction in the risk of progression or death, as reflected upon the increase of 6.1 months in median progression-free survival, indicates that pertuzumab may provide an avenue for achieving additional benefit for patients with HER2+. Moreover, pertuzumab seems to have a putative role in the management of patients with HER2 who are resistant to trastuzumab. The promising role of pertuzumab in the neoadjuvant and adjuvant settings remains to be further investigated and established in the future. © 2013 Elsevier Inc. All rights reserved.

INTRODUCTION: Geriatric depression is a heterogeneous disorder with a complex genetic background. Current first-line treatment of depression is associated with a lower therapeutic outcome in aged depressed patients, when compared to younger subjects. Research which has explored this inadequate response has highlighted several factors which have come into play with the pharmacogenetics of antidepressants in the elderly being a particular area of interest. AREAS COVERED: The authors perform a critical review of the English language articles from PubMed using search terms such as late-life/geriatric depression, antidepressants, pharmacogenetics, pharmacogenomics, pharmacokinetic, genetic, genotype, remission, therapy, treatment and polymorphism. EXPERT OPINION: The emerging clinical and pharmacogenetic data are slowly unveiling the importance of the genome - age interaction in antidepressant response. This data introduces a critical new parameter in personalized medicine. A profound analysis of the age factor in the pharmacogenetics of antidepressant response is imperative, in order to elucidate the clinical significance of these findings and thereby improve patient treatment in the elderly.

INTRODUCTION: Geriatric depression is a heterogeneous disorder with a complex genetic background. Current first-line treatment of depression is associated with a lower therapeutic outcome in aged depressed patients, when compared to younger subjects. Research which has explored this inadequate response has highlighted several factors which have come into play with the pharmacogenetics of antidepressants in the elderly being a particular area of interest. AREAS COVERED: The authors perform a critical review of the English language articles from PubMed using search terms such as late-life/geriatric depression, antidepressants, pharmacogenetics, pharmacogenomics, pharmacokinetic, genetic, genotype, remission, therapy, treatment and polymorphism. EXPERT OPINION: The emerging clinical and pharmacogenetic data are slowly unveiling the importance of the genome - age interaction in antidepressant response. This data introduces a critical new parameter in personalized medicine. A profound analysis of the age factor in the pharmacogenetics of antidepressant response is imperative, in order to elucidate the clinical significance of these findings and thereby improve patient treatment in the elderly.

INTRODUCTION: Geriatric depression is a heterogeneous disorder with a complex genetic background. Current first-line treatment of depression is associated with a lower therapeutic outcome in aged depressed patients, when compared to younger subjects. Research which has explored this inadequate response has highlighted several factors which have come into play with the pharmacogenetics of antidepressants in the elderly being a particular area of interest. AREAS COVERED: The authors perform a critical review of the English language articles from PubMed using search terms such as late-life/geriatric depression, antidepressants, pharmacogenetics, pharmacogenomics, pharmacokinetic, genetic, genotype, remission, therapy, treatment and polymorphism. EXPERT OPINION: The emerging clinical and pharmacogenetic data are slowly unveiling the importance of the genome - age interaction in antidepressant response. This data introduces a critical new parameter in personalized medicine. A profound analysis of the age factor in the pharmacogenetics of antidepressant response is imperative, in order to elucidate the clinical significance of these findings and thereby improve patient treatment in the elderly.

Molecular beam epitaxy has been employed to obtain Ga1−xMnxN films with x up to 10% and Curie temperatures TC up to 13 K. The magnitudes of TC and their dependence on x, TC(x)∝xm, where m=2.2±0.2, are quantitatively described by a tight-binding model of superexchange interactions and Monte Carlo simulations of TC. The critical behavior of this dilute magnetic insulator shows strong deviations from the magnetically clean case (x=1), in particular, (i) an apparent breakdown of the Harris criterion, (ii) a nonmonotonic crossover in the values of the susceptibility critical exponent γeff between the high temperature and critical regimes, and (iii) a smearing of the critical region, which can be explained either by the Griffiths effects or by macroscopic inhomogeneities in the spin distribution with a variance Δx=(0.2±0.1)%.

This phase II study is the first prospective evaluation of bortezomib-dexamethasone as second-line therapy for relapsed/refractory multiple myeloma. A total of 163 patients were enrolled to receive four cycles of bortezomibdexamethasone. Patients were investigator-assessed for response at cycle 5 Day 1, then treated as follows: responding patients received another four cycles of bortezomib-dexamethasone, while patients with stable disease were subsequently randomized to sequential treatment with a further four cycles of bortezomib-dexamethasone alone or with added cyclophosphamide or lenalidomide. The primary end point was response to sequential therapy; however, this could not be evaluated because investigator-assessed response rates to bortezomib-dexamethasone after four cycles were high, and an insufficient number of patients were randomized to sequential treatment per protocol. Among all 163 patients, validated best confirmed response rate was 66%, including 37% complete/very good partial responses; median response duration was 9.7 months. After a median follow up of 16.9 months, median time to progression and progression-free survival were 9.5 and 8.6 months, respectively; estimated 1-year overall survival was 81%. Median glomerular filtration rate improved from baseline during treatment. Among 58 patients with baseline glomerular filtration rate below 50 mL/min, 24 had renal responses. Grade 3/4 adverse events included: thrombocytopenia (17%), anemia (10%), constipation (6%), peripheral sensory neuropathy (5%), and polyneuropathy (5%). Overall, 57% of neuropathy events improved/resolved; median time to improvement was 2.1 months. These findings suggest bortezomib-dexamethasone represents an active, feasible second-line treatment option for patients with relapsed/refractory myeloma.. © 2013 Ferrata Storti Foundation.

Introduction: Phospholipases A2 have been implicated in various pathological conditions, such as rheumatoid arthritis, cardiovascular diseases, neurological disorders and cancer. The scientific community focuses on the search of potent and selective PLA2 inhibitors of each PLA2 class in order to identify novel medicinal agents. At present, only one lipoprotein-associated PLA2 (LpPLA2) inhibitor has reached Phase III clinical trials for the treatment of atherosclerosis. Areas covered: This review article focuses on the role of the most important PLA2s in inflammatory diseases and other severe pathological conditions presented in patent literature from June 2009 to September 2012. Expert opinion: Even though the role of each PLA2 in different diseases or pathological conditions is not yet definitively identified, the progress in the quest for potent and selective PLA2 inhibitors is exciting and the use of such inhibitors as medicinal agent looks now more promising than ever.