OBJECTIVES: Neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker for acute kidney injury. NGAL can be measured in both blood and urine. Apart from kidney injury, NGAL levels in both plasma and urine can be influenced by various pathological situations. Accurate evaluation and comparison of results deriving from clinical studies require robust assays, appropriate specimen handling and reference intervals that will reflect its levels in a healthy population for both biological matrices. METHODS: We report the analytical validation of a latex particle-enhanced turbidimetric immunoassay (PETIA) aimed to measure NGAL in plasma and urine on an automated biochemistry analyzer (ABBOTT-Architect-8000). Assay performance characteristics were evaluated using standard protocols. Urine and plasma specimen storage requirements were determined and reference ranges for blood and urine were determined using healthy controls. RESULTS: The assay is precise (total CV%<4.8%), and sensitive (limit of quantification: 8.4 ng/mL for plasma and 9.0 ng/mL for urine), showing no hook effect. Calibration is stable for at least 30 days. The assay showed excellent linearity over the studied interval (20-4450 ng/mL). The analyte is stable at 4 degrees C for at least 5 days, and at 20 degrees C for 4h. Gender specific reference ranges for plasma (male: 38.7-157.6 ng/mL, female: 24.4-142.5 ng/mL) and unisex for urine (<9.0-49.41 ng/mL) are proposed. CONCLUSION: Our data indicate that NGAL can be measured with adequate precision and sensitivity on automated biochemistry analyzers and its measurement could easily be added to a standard panel to screen kidney diseases

This study compares the differences in effectiveness of the five volleyball skills (serve, reception, attack, block, and dig) between men and women in high- level tournament games played at the last four consecutive Olympics. Results showed that men's and women's volleyball games are completely differentiated by two outcome measures. The first one is the higher proportion of faulty serves performed by men which is essentially attributable to the 19 cm difference in net height, while the second one derives from the fact that men outperform women at the execution of the attack.

Αντικείμενο του βιβλίου είναι η ανθρωπολογική μελέτη των κινητοποιήσεων στην πλατεία Συντάγματος το 2011, οι οποίες έγιναν γνωστές στον Τύπο ως το κίνημα των "Αγανακτισμένων". Σκοπός είναι η ανάδειξη της εμπειρίας των ανθρώπων που συμμετείχαν στην καθημερινότητα της ζωής στην Πλατεία και η σύνδεσή της με τα συναισθήματα και τη μουσική. Το βιβλίο βασίζεται στο εθνογραφικό υλικό που συλλέχθηκε από συνεντεύξεις και επιτόπια συμμετοχική παρατήρηση κατά τη διάρκεια των κινητοποιήσεων από τον Μάιο έως τον Αύγουστο του 2011.Η μουσική και τα συναισθήματα αποτελούν τους αναλυτικούς φακούς του βιβλίου. Ενισχύοντας σύγχρονες θεωρητικές τάσεις που υποστηρίζουν ότι τα συναισθήματα αποτελούν βασικό αντικείμενο έρευνας των κοινωνικών κινημάτων, το βιβλίο εστιάζει στην ποικιλία των συναισθημάτων που εκφράστηκαν στο Σύνταγμα και που δεν περιορίστηκαν στην "αγανάκτηση". Σε αντίθεση με τη σχετική βιβλιογραφία για τα κοινωνικά κινήματα που αποδίδει κυρίαρχο ρόλο στο τραγούδι, στο Σύνταγμα κυριάρχησε ο συλλογικός μουσικός και ρυθμικός αυτοσχεδιασμός.Η πλατεία Συντάγματος αποτελεί ξεκάθαρα μια "ζώνη πολιτισμικού αυτοσχεδιασμού", όπως την ορίζει ο ανθρωπολόγος Ντέιβιντ Γκραίμπερ, καθώς ετερόκλητοι άνθρωποι θέλησαν να βρουν τρόπους να συνυπάρξουν, παρά τις διαφορές τους, να "πειραματιστούν" και να "αυτοσχεδιάσουν" χωρίς να ταυτίζονται ιδεολογικά. Το πολιτικό συμπορεύτηκε με το μουσικό, συνθέτοντας μια νέα κουλτούρα κοινωνικής συνύπαρξης και εκφράζοντας μια νέα σχέση των ανθρώπων με τα κοινά. (Από την παρουσίαση στο οπισθόφυλλο του βιβλίου)

Background/aim: In light of the controversial published literature, this study aims to examine the potential prognostic role of AR immunohistochemical expression in triple negative breast cancer (TNBC). Patients and methods: Ninety patients with TNBC were included in this study; the associations between AR expression (Allred score), clinicopathological variables (stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression), and overall survival were evaluated. Results: AR expression was not associated with stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression. AR immunopositivity was not associated with overall survival either at the univariate or at the multivariate Cox regression analysis (multivariate hazard ratio =0.66, 95% confidence interval: 0.26–1.70, P=0.393). Conclusion: AR expression does not seem to play a prognostic role in TNBC. © 2015 Giannos et al.

The fumarylacetoacetate hydrolase (FAH) protein superfamily of metabolic enzymes comprises a diverse set of enzymatic functions, including ss-diketone hydrolases, decarboxylases, and isomerases. Of note, the FAH superfamily includes many prokaryotic members with very distinct functions that lack homologs in eukaryotes. A prokaryotic member of the FAH superfamily, referred to as Cg1458, was shown to encode a soluble oxaloacetate decarboxylase (ODx). Based on sequence homologies to Cg1458, we recently identified human FAH domain containing protein-1 (FAHD1) as the first eukaryotic oxaloacetate decarboxylase. The physiological functions of ODx in eukaryotes remain unclear. Here we have probed the function of fahd-1, the nematode homolog of FAHD1, in the context of an intact organism. We found that mutation of fahd-1 resulted in reduced brood size, a deregulation of the egg laying process and a severe locomotion deficit, characterized by a reduced frequency of body bends, reduced exploratory movements and reduced performance in an endurance exercise test. Notably, mitochondrial function was altered in the fahd-1(tm5005) mutant strain, as shown by a reduction of mitochondrial membrane potential and a reduced oxygen consumption of fahd-1(tm5005) animals. Mitochondrial dysfunction was accompanied by lifespan extension in worms grown at elevated temperature; however, unlike in mutant worms with a defect in the electron transport chain, the mitochondrial unfolded protein response was not upregulated in worms upon inactivation of fahd-1. Together these data establish a role of fahd-1 to maintain mitochondrial function and consequently physical activity in nematodes.

Employing first-principles electronic-structure calculations in conjunction with the frozen-magnon method, we calculate exchange interactions, spin-wave dispersion, and spin-wave stiffness constants in inverse-Heusler-based spin gapless semiconductor (SGS) compounds Mn2CoAl, Ti2MnAl, Cr2ZnSi, Ti2CoSi, and Ti2VAs. We find that their magnetic behavior is similar to the half-metallic ferromagnetic full-Heusler alloys, i.e., the intersublattice exchange interactions play an essential role in the formation of the magnetic ground state and in determining the Curie temperature T-c. All compounds, except Ti2CoSi, possess a ferrimagnetic ground state. Due to the finite energy gap in one spin channel, the exchange interactions decay sharply with the distance, and hence magnetism of these SGSs can be described considering only nearest-and next-nearest-neighbor exchange interactions. The calculated spin-wave dispersion curves are typical for ferrimagnets and ferromagnets. The spin-wave stiffness constants turn out to be larger than those of the elementary 3d ferromagnets. Calculated exchange parameters are used as input to determine the temperature dependence of the magnetization and Tc of the SGSs. We find that the Tc of all compounds is much above the room temperature. The calculated magnetization curve for Mn2CoAl as well as the Curie temperature are in very good agreement with available experimental data. This study is expected to pave the way for a deeper understanding of the magnetic properties of the inverse-Heusler-based SGSs and enhance the interest in these materials for application in spintronic and magnetoelectronic devices.

The recent revision of ISO15189 has further strengthened its position as the standard for accreditation for medical laboratories. Both for laboratories and their customers it is important that the scope of such accreditation is clear. Therefore the European co-operation for accreditation (EA) demands that the national bodies responsible for accreditation describe the scope of every laboratory accreditation in a way that leaves no room for doubt about the range of competence of the particular laboratories. According to EA recommendations scopes may be fixed, mentioning every single test that is part of the accreditation, or flexible, mentioning all combinations of medical field, examination type and materials for which the laboratory is competent. Up to now national accreditation bodies perpetuate use of fixed scopes, partly by inertia, partly out of fear that a too flexible scope may lead to over-valuation of the competence of laboratories, most countries only use fixed scopes. The EA however promotes use of flexible scopes, since this allows for more readily innovation, which contributes to quality in laboratory medicine. In this position paper, the Working Group Accreditation and ISO/CEN Standards belonging to the Quality and Regulation Committee of the EFLM recommends using an approach that has led to successful introduction of the flexible scope for ISO15189 accreditation as intended in EA-4/17 in The Netherlands. The approach is risk-based, discipline and competence-based, and focuses on defining a uniform terminology transferable across the borders of scientific disciplines, laboratories and countries

In preclinical studies screening for novel antidepressants, male and female animals should be used. However, in a widely used antidepressant test, the forced swim test (FST), sex differences between males and females are not consistent. These discrepancies may discourage the inclusion of females in FST studies. In order to overcome this problem and provide a detailed insight regarding the use of female animals in the FST, we designed the following experiment and we performed a thorough analysis of the relevant literature. Male and female Wistar adult rats were subjected to the FST and sertraline was used as an antidepressant in two doses (10 mg/kg and 40 mg/kg, 3 injections in 24 h). Rodents were subjected in the two FST sessions during all possible combinations of the estrous cycle stages. We found that females exhibited higher levels of immobility than males and this sex difference was alleviated following antidepressant treatment. Sertraline at both doses enhanced swimming in both sexes, but females appeared more responsive to lower sertraline doses regarding immobility levels. Surprisingly, the high sertraline dose enhanced climbing particularly in proestrous and diestrous. Marked sex differences were also observed in the frequency of head swinging, with females exhibiting lower counts than males. Conclusively, when screening for new antidepressants, it is recommended to use standard FST procedures and if possible to include females in all phases of the cycle. Using only one dose of an investigational drug in females in certain phases of the cycle could result to false negative results.

In preclinical studies screening for novel antidepressants, male and female animals should be used. However, in a widely used antidepressant test, the forced swim test (FST), sex differences between males and females are not consistent. These discrepancies may discourage the inclusion of females in FST studies. In order to overcome this problem and provide a detailed insight regarding the use of female animals in the FST, we designed the following experiment and we performed a thorough analysis of the relevant literature. Male and female Wistar adult rats were subjected to the FST and sertraline was used as an antidepressant in two doses (10 mg/kg and 40 mg/kg, 3 injections in 24 h). Rodents were subjected in the two FST sessions during all possible combinations of the estrous cycle stages. We found that females exhibited higher levels of immobility than males and this sex difference was alleviated following antidepressant treatment. Sertraline at both doses enhanced swimming in both sexes, but females appeared more responsive to lower sertraline doses regarding immobility levels. Surprisingly, the high sertraline dose enhanced climbing particularly in proestrous and diestrous. Marked sex differences were also observed in the frequency of head swinging, with females exhibiting lower counts than males. Conclusively, when screening for new antidepressants, it is recommended to use standard FST procedures and if possible to include females in all phases of the cycle. Using only one dose of an investigational drug in females in certain phases of the cycle could result to false negative results.

© Springer-Verlag London 2015. Aim: To present the technique and the results of treatment of vaginal aplasia with the use of Frank's Dilators and to critically report its potential advantages and limitations.Brief description of the reviewed data: Vaginal dilation involves the insertion of graduated dilators in the vaginal dimple and applying pressure. It is recognized as the first line method for creating a vagina in women with Mayer Rokitansky Kuster Hauser syndrome (MRKH) and Complete Androgen Insensitivity Syndrome (CAIS). An 80 {%} success rate is reported with improvement of sexual satisfaction and anxiety scores. There are only few complications reported in the literature making it a low risk and low cost method to create a vagina. Clinical implications: Vaginal dilation therapy should be offered to all women presenting with MRKH or CAIS prior to embarking on a surgical vaginoplasty. Adequate psychological support during the process is likely to improve success rates as well as the overall wellbeing of patients diagnosed with uterovaginal aplasia.Open issues for further research: More research is required on long term outcomes of vaginal dilation therapy as well as on the comparison between surgical and conservative methods to create a vagina.

Male breast cancer is an uncommon malignancy; little is known regarding hormonal manipulations for tamoxifen-resistant male breast cancer patients. This is the first pooled analysis of the literature to synthesize all available data and to evaluate the efficacy and safety of fulvestrant in male breast cancer. This study was performed in accordance with the PRISMA guidelines. All studies that examined the efficacy of fulvestrant in male breast cancer, regardless of sample size, were considered eligible. The search strategy retrieved 31 articles; of these, five articles were eligible (23 patients) for this pooled analysis. The mean age of the study sample was 63.1 years. Adjuvant hormonal treatment was administered in 87.5 % of cases. Fulvestrant was given as first or second line in 40 % of patients, while as third line or beyond in 60 % of patients. 79.0 % of patients at fulvestrant administration had visceral metastases. Regarding best response, in 26.1 % PR was achieved, in 47.8 % of cases SD was recorded, whereas in 26.1 % of patients PD was noted. The median PFS was equal to 5 months. No grade 3 and 4 adverse events were recorded; of note, hot flashes were reported in 18.2 % of male breast cancer patients. Fulvestrant may potentially play a promising role in the optimal therapeutic strategy for male patients with breast cancer diagnosis. However, further clinical and pharmacokinetic investigations are more than warranted before fulvestrant use becomes a common practice in male breast cancer patients. © 2014, Springer Science+Business Media New York.

In the scope of the France-Greek program PLATON n° 30409XH “EMerChanCy”, this work focuses on the beachrocks of Paros and Naxos Islands, in central Cyclades, Aegean Sea, Greece, in an attempt to study their geochemistry and interpret their palaeoenvironmental significance. Beachrocks are coastal sedimentary formations, consisting of beach sediments that are relatively quickly cemented through the precipitation of CaCO3. However, debate still exists concerning their depositional environment, and therefore, their use as indicators for sea-level changes. For the aim of the present study, representative bulk samples from both islands were analyzed for their mineralogical (XRD) and chemical compositition (SEM). Chemical analyses were performed by XRF . The cement agent and the fine sand/clay fraction of the samples mainly consist of authigenic magnesian calcite, which commonly precipitates in shallow marine environments, especially in high concentration of Ca2+(>4 mol% CaCO3 or 1.2 wt.%). Furthermore, a series of clastic silicate and alumino-silicate minerals are detected. The predominant coarse fragments hosted within cement material are quartz, albite and K-feldspar. The texture of the beachrock samples varies from almost homogeneous sandstone to a mixture of lithologies, such as massive gravel, sandstone and claystone. Most of the grains are flattened and only rarely angular pieces of siliceous rocks occur, hosted in the fine-grained Mg-calcite cement. This grain size and shape is indicative of the genetic environment of beachrocks, implying the maturity level of cementation from early stage to modern situation. The beachrock samples derived from various depositional periods and depths, from the front and end slabs. The beachrocks were also correlated with stratigraphical material from boreholes and archaeological remains from the study area in an attempt to understand the coastal changes during the late Holocene in Central Cyclades.

We conducted a pooled analysis of 869 individual newly diagnosed elderly patient data from 3 prospective trials. At diagnosis, a geriatric assessment had been performed. An additive scoring system (range 0-5), based on age, comorbidities, and cognitive and physical conditions, was developed to identify 3 groups: fit (score = 0, 39%), intermediate fitness (score = 1,31%), and frail (score ≥2, 30%). The 3-year overall survivalwas 84%in fit, 76% in intermediate-fitness (hazard ratio [HR], 1.61; P = .042), and 57% in frail (HR, 3.57; P < .001) patients. Thecumulative incidence of grade ≥3 nonhematologic adverse events at 12 months was 22.2%in fit, 26.4%in intermediate-fitness (HR, 1.23; P = .217), and 34.0%in frail (HR, 1.74; P < .001) patients. The cumulative incidence of treatment discontinuation at 12months was 16.5%in fit, 20.8%in intermediate-fitness (HR, 1.41; P = .052), and 31.2% in frail (HR, 2.21; P < .001) patients. Our frailty score predicts mortality and the risk of toxicity in elderly myeloma patients. The International Myeloma Working group proposes this score for the measurement of frailty in designing future clinical trials. These trials are registered at www.clinicaltrials.gov as #NCT01093136 (EMN01), #NCT01190787 (26866138MMY2069), and #NCT01346787 (IST-CAR-506).

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) subtype CRF01_AE originated in Africa and then passed to Thailand, where it established a major epidemic. Despite the global presence of CRF01_AE, little is known about its subsequent dispersal pattern. METHODS: We assembled a global data set of 2736 CRF01_AE sequences by pooling sequences from public databases and patient-cohort studies. We estimated viral dispersal patterns, using statistical phylogeographic analysis run over bootstrap trees estimated by the maximum likelihood method. RESULTS: We show that Thailand has been the source of viral dispersal to most areas worldwide, including 17 of 20 sampled countries in Europe. Japan, Singapore, Vietnam, and other Asian countries have played a secondary role in the viral dissemination. In contrast, China and Taiwan have mainly imported strains from neighboring Asian countries, North America, and Africa without any significant viral exportation. DISCUSSION: The central role of Thailand in the global spread of CRF01_AE can be probably explained by the popularity of Thailand as a vacation destination characterized by sex tourism and by Thai emigration to the Western world. Our study highlights the unique case of CRF01_AE, the only globally distributed non-B clade whose global dispersal did not originate in Africa.

Background: International collaborative research is a mechanism for improving the development of dis-ease- specific therapies and for improving health at the population level. However, limited data are available to assess the trends in research output related to orphan diseases. Methods and Findings: We used bibliometric mapping and clustering methods to illustrate the level of fragmentation in myeloma research and the development of collaborative efforts. Publication data from Thomson Reuters Web of Science were retrieved for 2005-2009 and followed until 2013. We created a database of multiple myeloma publications, and we analysed impact and coauthorship density to identify scientific collaborations, developments, and international key players over time. The global annual publication volume for studies on multiple myeloma increased from 1,144 in 2005 to 1,628 in 2009, which represents a 43% increase. This increase is high compared to the 24% and 14% increases observed for lymphoma and leukaemia. The major proportion (>90% of publications) was from the US and EU over the study period. The output and impact in terms of citations, identified several successful groups with a large number of intra-cluster collaborations in the US and EU. The US-based myeloma clusters clearly stand out as the most productive and highly cited, and the European Myeloma Network members exhibited a doubling of collaborative publications from 2005 to 2009, still increasing up to 2013. Conclusion and Perspective: Multiple myeloma research output has increased substantially in the past decade. The fragmented European myeloma research activities based on national or regional groups are progressing, but they require a broad range of targeted research investments to improve multiple myeloma health care. © 2015 Andersen et al.

This paper investigates two tense-based constructions in English and Greek and one complementation construction in Greek, whose import is to effect a deictic shift and allow narration to proceed from the point of view of the narrated events and a participant therein. In addition to the individual formal and discourse-pragmatic properties of the patterns at hand, I focus on properties of the embedding context, showing that these unrelated constructions impose similar formal and interpretational requirements. This, in turn, supports the statement of generalizations at the level of genre, in this case ‘empathetic narration’ as a special kind of narration that departs from the default past narrative deictically anchored to the narrator and the conversational coordinates. While the analysis adopts a bottom-up, language-driven approach to genre, it also refutes an exhaustive equation with linguistic conventions, arguing that a Bakhtinian view of genre, which includes both linguistic and socio-cultural dimensions, is more appropriate for the data at hand.

The aim of the current study was to compare the biological activities of total polar lipids (TPL) and thin-layer chromatography (TLC) polar lipid fractions of sardine fillet and cod liver oil against atherogenesis. TPL and TLC polar lipid fractions obtained from these two sources were assessed for their ability to inhibit the platelet-activating-factor (PAF)-induced platelet aggregation (PAF-antagonists) or to induce platelet aggregation (PAF-agonists), since PAF plays a crucial role in the initiation and development of atherosclerosis. This study focused on the polar lipids since previous studies have underlined that the antithrombotic properties of foodstuffs are mainly attributed to polar lipid micro-constituents. TPL of sardine fillet induced platelet aggregation, while TPL of cod liver had a bimodal effect on platelets. TLC polar lipid fractions of both samples exhibited in vitro aggregatory and inhibitory activity towards platelets. However, TLC sardine polar lipid fractions showed stronger in vitro antithrombotic activities than the cod liver oil ones. These data constitute evidence of the putative contribution of fish polar lipids against cardiovascular diseases, underling firstly the beneficial effect of fish and fish lipids as functional foodstuffs against atherogenesis and secondly the more important role of sardine polar lipids as opposed to cod liver oil.

This study aims to analyse the economic efficiency of Greek small and medium retail enterprises before and after the crisis that started in 2008. Based on the Accounting Equation, we use Data Envelopment Analysis (DEA) to estimate variable returns of scale efficiency scores and to conclude on specific characteristics that efficient companies have, for example, on capital structure. Our results from the DEA application show a high degree of inefficiency. We found that SMEs on the islands are more efficient than those on the mainland and that SMEs in the cities are the least efficient. Size seems to be important, more so on the islands and on the mainland than in the cities. We conclude that companies should act more conservatively in terms of operating cost when the first signs of a recession appear. In addition, during a recession period, companies that have evidences that their operations will continue positively should strengthen their operations by raising more own capital. Finally, our study clarifies four issues: the efficiency of retail companies in a period of growth and a period of recession, focusing on SMEs that operate in different regions, connecting Accounting Equation and DEA and adding acid ratio as an output in our model.

In recent years the costs of hospital care in developed countries absorbed a high proportion of total health resources. In Greece, after the establishment of the National Health System (NHS), funding for hospitals comes mainly from the state budget, and social insurance, therefore auditing of hospital cost is imperative to ensure their viability, especially at this time when the country is tested by economic crisis. Overtime many factors for the increase of hospital cost have been mentioned, such as the rapid development of medical technology, the low level of organization of the hospital system and the low productivity of human resources. The problem of rising health expenditure over the past decades is a worldwide phenomenon and it has brought about many changes in traditional retrospective methods for financing in the hospital sector, with prospective financial forms that combine patient composition and needs, and the productive activity of hospital need to the rationalization and contain expenditures. The system of Diagnosis Related Groups was a revolutionary success over the past decades and has now achieved worldwide recognition.

Factors associated with information retrieval have been tested in the present pilot project, suggested an appropriate instrument chosen from previous research. The purpose of this paper is to access the internal validity and the internal consistency reliability of the research instrument. The questionnaire determine the information needs, information seeking behavior, the adequacy of online information sources, examine access, training received, barriers in using information technology and research utilization. The pilot questionnaire was distributed to nurses and physicians working in Greek hospitals and was tested for its validity and reliability coefficients.

Despite the fact that several natural products (e.g. crude extracts or purified compounds) have been found to activate cell antioxidant responses and/or delay cellular senescence the effect(s) of small peptides on cell viability and/or modulation of protective mechanisms (e.g. the proteostasis network) remain largely elusive. We have thus studied a hexapeptide (Hexapeptide-11) of structure Phe-Val-Ala-Pro-Phe-Pro (FVAPFP) originally isolated from yeast extracts and later synthesized by solid state synthesis to high purity. We show herein that Hexapeptide-11 exhibits no significant toxicity in normal human diploid lung or skin fibroblasts. Exposure of fibroblasts to Hexapeptide-11 promoted dose and time-dependent activation of proteasome, autophagy, chaperones and antioxidant responses related genes. Moreover, it promoted increased nuclear accumulation of Nrf2; higher expression levels of proteasomal protein subunits and increased proteasome peptidase activities. In line with these findings we noted that Hexapeptide-11 conferred significant protection in fibroblasts against oxidative-stress-mediated premature cellular senescence, while at in vivo skin deformation assays in human subjects it improved skin elasticity. Finally, Hexapeptide-11 was found to induce the activity of extracellular MMPs and it also suppressed cell migration. Our presented findings indicate that Hexapeptide-11 is a promising anti-ageing agent.

Chronic hepatitis C virus (HCV) infection is a leading cause of liver related morbidity and mortality. In many countries, there is a lack of comprehensive epidemiological data that are crucial in implementing disease control measures as new treatment options become available. Published literature, unpublished data and expert consensus were used to determine key parameters, including prevalence, viremia, genotype and the number of patients diagnosed and treated. In this study of 15 countries, viremic prevalence ranged from 0.13% in the Netherlands to 2.91% in Russia. The largest viremic populations were in India (8 666 000 cases) and Russia (4 162 000 cases). In most countries, males had a higher rate of infections, likely due to higher rates of injection drug use (IDU). Estimates characterizing the infected population are critical to focus screening and treatment efforts as new therapeutic options become available.

Objectives. We examined HIV prevalence and risk factors among injection drug users (IDUs) in Athens, Greece, during an HIV outbreak. Methods. We used respondent-driven sampling (RDS) to recruit 1404 IDUs to the Aristotle intervention in August to October 2012. We interviewed participants and tested for HIV. We performed bivariate and multivariate analyses. Results. Estimated HIV prevalence was 19.8% (RDS-weighted prevalence = 14.8%). Odds of infection were 2.3 times as high in homeless as in housed IDUs and 2.1 times as high among IDUs who injected at least once per day as among less frequent injectors (both, P < .001). Six percent of men and 23.5% of women reported transactional sex in the past 12 months, and condom use was low. Intercourse with non-IDUs was common (53.2% of men, 25.6% of women). Among IDUs who had been injecting for 2 years or less the estimated incidence rate was 23.4 new HIV cases per 100 person-years at risk. Conclusions. Efforts to reduce HIV transmission should address homelessness as well as scaling up prevention services, such as needle and syringe distribution and other risk reduction interventions.

Objectives. We examined HIV prevalence and risk factors among injection drug users (IDUs) in Athens, Greece, during an HIV outbreak. Methods. We used respondent-driven sampling (RDS) to recruit 1404 IDUs to the Aristotle intervention in August to October 2012. We interviewed participants and tested for HIV. We performed bivariate and multivariate analyses. Results. Estimated HIV prevalence was 19.8% (RDS-weighted prevalence = 14.8%). Odds of infection were 2.3 times as high in homeless as in housed IDUs and 2.1 times as high among IDUs who injected at least once per day as among less frequent injectors (both, P < .001). Six percent of men and 23.5% of women reported transactional sex in the past 12 months, and condom use was low. Intercourse with non-IDUs was common (53.2% of men, 25.6% of women). Among IDUs who had been injecting for 2 years or less the estimated incidence rate was 23.4 new HIV cases per 100 person-years at risk. Conclusions. Efforts to reduce HIV transmission should address homelessness as well as scaling up prevention services, such as needle and syringe distribution and other risk reduction interventions.

A hallmark of human and experimental heart failure is deficient sarcoplasmic reticulum (SR) Ca-uptake reflecting impaired contractile function. This is at least partially attributed to dephosphorylation of phospholamban by increased protein phosphatase 1 (PP1) activity. Indeed inhibition of PP1 by transgenic overexpression or gene-transfer of constitutively active inhibitor-1 improved Ca-cycling, preserved function and decreased fibrosis in small and large animal models of heart failure, suggesting that inhibitor-1 may represent a potential therapeutic target. We recently identified a novel human polymorphism (G109E) in the inhibitor-1 gene with a frequency of 7% in either normal or heart failure patients. Transgenic mice, harboring cardiac-specific expression of G109E inhibitor-1, exhibited decreases in contractility, Ca-kinetics and SR Ca-load. These depressive effects were relieved by isoproterenol stimulation. Furthermore, stress conditions (2Hz +/- Iso) induced increases in Ca-sparks, Ca-waves (60% of G109E versus 20% in wild types) and after-contractions (76% of G109E versus 23% of wild types) in mutant cardiomyocytes. Similar findings were obtained by acute expression of the G109E variant in adult cardiomyocytes in the absence or presence of endogenous inhibitor-1. The underlying mechanisms included reduced binding of mutant inhibitor-1 to PP1, increased PP1 activity, and dephosphorylation of phospholamban at Ser16 and Thr17. However, phosphorylation of the ryanodine receptor at Ser2808 was not altered while phosphorylation at Ser2814 was increased, consistent with increased activation of Ca/calmodulin-dependent protein kinase II (CaMKII), promoting aberrant SR Ca-release. Parallel in vivo studies revealed that mutant mice developed ventricular ectopy and complex ventricular arrhythmias (including bigeminy, trigeminy and ventricular tachycardia), when challenged with isoproterenol. Inhibition of CaMKII activity by KN-93 prevented the increased propensity to arrhythmias. These findings suggest that the human G109E inhibitor-1 variant impairs SR Ca-cycling and promotes arrhythmogenesis under stress conditions, which may present an additional insult in the compromised function of heart failure carriers.

We report first results from our XMM-Newton observation of IGR J01217-7257 performed on November 7, 2015. This transient in the Small Magellanic Cloud (Coe et al. 2014, ATel #5806) was found to be in a new outburst during Integral observations end of October 2015 (Coe et al. 2015, ATel #8246).

The elucidation of the molecular mechanisms that lead to the development of metabolic syndrome, a complex of pathological conditions including type-2 diabetes, hypertension, and cardiovascular diseases, is an important issue with high biological significance and requires accurate methods capable of monitoring lipid storage distribution and dynamics in vivo. In this study, the nonlinear phenomena of second and third harmonic generation (SHG, THG) have been employed simultaneously as label-free, nondestructive diagnostic techniques, for the monitoring and the complementary three-dimensional (3D) imaging and analysis of the muscular areas and the lipid content localization. THG microscopy was used as a quantitative tool in order to record the accumulation of lipids in nonadipose tissues in the pharyngeal muscles of 18 Caenorhabditis elegans (C. elegans) specimens, while the SHG imaging provided the detailed anatomical information about the structure of the muscles. The ectopic accumulation of fat on the pharyngeal muscles increases in wild-type (N2) C. elegans between 1 and 9 days of adulthood. This suggests a correlation of ectopic fat accumulation with the process of aging. Our results can contribute to the unraveling of the link between the deposition of ectopic fat and aging, but mainly to the validation of SHG and THG microscopy modalities as new, noninvasive tools to localize and quantify selectively lipid formation and distribution.

The International Medical Informatics Association (IMIA) is the world body for biomedical and health informatics (BMHI). IMIA accreditation program allows the health and medical informatics programs around the world to reach to an international level. Staffs (professors, students, education programmes directors, others) that work on the accredited BMHI programs will have the opportunity to be engaged with organizations that possess a world-class research and education profile from other countries, which will have great impacts on their field at their institutions, within their country providing the high quality overall health services. IMIA accreditation procedure is usually a long process and slightly complicated. The goal of this paper is to illustrate and to simplify the IMIA accreditation process to increase the success of the applicants. Toward more dynamic IMIA accreditation procedure, the paper presents 4 steps: translation, IMIA-Accreditation Step by Step Guideline, Questions and Answers, and finally the (new) Labelling System.

© 2015, Springer Science+Business Media New York. The consequences of living in single-parent households on children's wellbeing are well documented, but less is known about the impact of living in single-mother households among children with high familial risk for depression. Utilizing data from an ongoing three-generation study of high-risk families, this preliminary study examined a sample of 161 grandchildren of probands diagnosed with major depressive disorder, comparing those in single-parent households to those in dual-parent households with household status defined as the full-time presence of a resident male in the home. High-risk children were compared across households in terms of psychiatric diagnoses (measured by Schedule for Affective Disorders and Schizophrenia for School-Age Children; K-SADS-PL) and global functioning (assessed by Global Assessment Scale, child version; C-GAS). Results indicated that high-risk children in single-parent households had 4.7 times greater odds for developing a mood disorder and had significantly lower mean C-GAS scores (p = 0.01) compared to those in dual-parent households. Differences remained significant when controlling for household income, child's age, and either parent's depression status. There were no significant differences between high-risk children across households when household status was instead defined as legal marital status. This study has several limitations: sample size was small, probands were recruited from a clinical population, and participants had not passed completely through the period of risk for adult psychiatric disorders. These findings point towards the importance of identifying and closely monitoring children at risk for depression, particularly if they reside in households without a resident father figure.

Pomalidomide is a distinct oral IMiD® immunomodulatory agent with direct antimyeloma, stromal-support inhibitory, and immunomodulatory effects. The pivotal, multicenter, open-label, randomized phase 3 trial MM-003 compared pomalidomide + low-dose dexamethasone vs high-dose dexamethasone in 455 patients with refractory or relapsed and refractory multiple myeloma after failure of bortezomib and lenalidomide treatment. Initial results demonstrated significantly longer progression-free survival and overall survival with an acceptable tolerability profile for pomalidomide + low-dose dexamethasone vs high-dose dexamethasone. This secondary analysis describes patient outcomes by treatment history and depth of response. Pomalidomide + low-dose dexamethasone significantly prolonged progression-free survival and favored overall survival vs high-dose dexamethasone for all subgroups analyzed, regardless of prior treatments or refractory status. Both univariate and multivariate analyses showed that no variable relating to either the number (≤ or > 3) or type of prior treatment was a significant predictor of progression-free survival or overall survival. No cross-resistance with prior lenalidomide or thalidomide treatment was observed. Patients achieving a minimal response or better to pomalidomide + low-dose dexamethasone treatment experienced a survival benefit, which was even higher in those achieving at least a partial response (17.2 and 19.9 months, respectively, as compared with 7.5 months for patients with less than minimal response). These data suggest that pomalidomide + low-dose dexamethasone should be considered a standard of care in patients with refractory or relapsed and refractory multiple myeloma regardless of prior treatment. ClinicalTrials.gov: NCT01311687; EudraCT: 2010-019820-30. © 2015 Ferrata Storti Foundation.

The growing period of the deep-rooted, winter-deciduous Capparis spinosa (caper) coincides with the dry season, in the Mediterranean Basin. Roots of wild shrubs of C. spinosa penetrated cracks of a pumice substrate and lengthened in the subterranean environment of the ancient catacombs of Milos Island (Greece); therein, they reached depths of up to 20 m and exploited water present in deep soil layers. Elevated water potential (Ψ) was measured in root segments (Ψr = −0.35 ± 0.06 MPa), a few centimetres from the root apices of C. spinosa found in the catacombs during the dry season. Also, estimates of foliar predawn water potential and gas exchange components, as well as of nocturnal floral water potential of C. spinosa grown on slopes above the subterranean monument were high and reflected the efficiency of roots in retaining acquisition of water from deep soil layers, during the dry season.

BACKGROUND & AIMS: The risk of hepatocellular carcinoma (HCC) in Caucasian patients with chronic hepatitis B (CHB), treated with entecavir (ETV) or tenofovir (TDF), is unclear. We evaluated the incidence and predictors of HCC and the accuracy of existing HCC risk scores in Caucasian CHB patients receiving ETV/TDF. METHODS: This large, multicentre, retrospective cohort study included 1666 adult Caucasian CHB patients under ETV/TDF for 39 months. CHB without cirrhosis, compensated and decompensated cirrhosis were present in 67%, 39%, and 3% of patients, respectively. The predictability of baseline parameters and three risk scores (GAG-HCC, CU-HCC, and REACH-B), developed in Asian patients, was assessed. RESULTS: The cumulative probability of HCC was 1.3%, 3.4%, and 8.7% at year-1, year-3, and year-5 after ETV/TDF onset. Older age and lower platelets were strong independent HCC predictors in the total population and in the subgroups of cirrhotic and non-cirrhotic patients, while liver disease severity was an independent HCC predictor in the total population and in the cirrhotics. GAG-HCC, CU-HCC, and REACH-B risk scores were associated with HCC development only in the univariable but not in the multivariable analyses and offered poor to modest predictability. CONCLUSIONS: HCC can still develop in Caucasian CHB patients treated with ETV/TDF. Besides the well-known predictors of HCC, such as older age, male gender and more advanced liver disease, lower platelets represent an independent factor of higher HCC risk. The applicability and predictability of HCC risk scores developed in Asian patients are poor or modest in Caucasian CHB patients, for whom different risk scores are required.

© 2015 European Society of Endocrinology. Objective: We aimed to evaluate the association between thyroid hormones and indices of obesity in a sample of euthyroid postmenopausal women. Design: Cross-sectional study. Methods: Serum levels of TSH, free triiodothyronine (FT3), and free thyroxine (FT4) as well as BMI and waist:hip ratio (WHR) were evaluated in 194 healthy euthyroid postmenopausal women. Ultrasonography was used to assess abdominal fat layers (subcutaneous fat (SF), preperitoneal fat (PF), and SF:PF ratio). Indices of adiposity were defined as high vs low depending on the median value of the assessed parameters. Results: After multivariate adjustment for traditional risk factors, lower FT4 levels and a higher FT3:FT4 ratio predicted higher SF mass (FT4, Exp(β)=0.035, P=0.020 and FT3:FT4, Exp(β)=2.374, P=0.018), whereas higher FT3 predicted higher PF mass (Exp(β)=2.815, P=0.032). Women with FT3:FT4 above the highest quartile had a significantly higher SF mass as compared to women in the lowest quartile (1.81±0.62 cm vs 1.54∓0.46 cm, P=0.027). BMI had a positive independent association with TSH (Exp(β)=1.829, P=0.018). Finally, FT3 was significantly associated with SF mass among women with higher BMI (FT3, β=0.259, P=0.040) and women with higher WHR (β=0.309, P=0.020) but not among women with lower BMI or WHR values. Conclusion: Thyroid hormone levels, and in particular FT3, were independently associated with SF and PF in euthyroid postmenopausal women, and this association was mainly evident in women with higher BMIs. On the other hand, among traditional indices of adiposity, only TSH was positively associated with BMI. Larger prospective studies are needed to evaluate the significance of the present findings.

BACKGROUND: Mesial protraction of mandibular posterior teeth requires increased anchorage to avoid undesired tooth movements. Orthodontic mini-implants have become a popular and successful way to increase skeletal anchorage in such cases. However, mini-implants may cause injury to adjacent teeth or anatomical structures and may lead to tissue inflammation. Induced ankylosed primary teeth have been used in the past as abutments for the protraction of the maxilla in cases of maxillary retrognathism. However, this technique has not been described in the literature for the protraction of mandibular molars. The aim of this paper is to present, through a case report, an alternative to mini-implant devices to maximize anchorage in the mandible by inducing ankylosis on a primary molar. FINDINGS: A 13-year-old female with class II right malocclusion, deep bite, and congenitally missing right second premolars was referred for orthodontic treatment. Treatment plan involved removal of the primary teeth and mesial protraction of the posterior. In the mandible, ankylosis was induced on the retained primary second molar by extraction, bisection, replantation of the mesial part after endodontic treatment, and bonding of a rigid splint. Ankylosis was diagnosed after 10 weeks and a closing T-loop sectional wire was inserted to move the permanent first molar mesially. At 6 months, the remaining space was closed using elastic chain on a rectangular stainless steel wire with tip-back bends, supported by class II elastics. CONCLUSIONS: Induced ankylosis of primary teeth can be an alternative to orthodontic mini-implants in selected cases, with minimal risks and maximum biocompatibility.

The Kolumbo submarine volcano, located 7 km northeast of the island of Santorini, is part of Santorini’s volcanic complex in the south Aegean Sea, Greece. Kolumbo’s last eruption was in 1650 AD. However, a unique and active hydrothermal vent field has been revealed in the northern part of its crater floor during an oceanographic survey by remotely operated vehicles (ROVs) in 2006. In the present study, conductivity-temperature-depth (CTD) data collected by ROV Hercules during three oceanographic surveys onboard E/V Nautilus in 2010 and 2011 have served to investigate the distribution of physicochemical properties in the water column, as well as their behavior directly over the hydrothermal field. Additional CTD measurements were carried out in volcanic cone 3 (VC3) along the same volcanic chain but located 3 km northeast of Kolumbo where no hydrothermal activity has been detected to date. CTD profiles exhibit pronounced anomalies directly above the active vents on Kolumbo’s crater floor. In contrast, VC3 data revealed no such anomalies, essentially resembling open-sea (background) conditions. Steep increases of temperature (e.g., from 16 to 19 °C) and conductivity near the maximum depth (504 m) inside Kolumbo’s cone show marked spatiotemporal correlation. Vertical distributions of CTD signatures suggest a strong connection to Kolumbo’s morphology, with four distinct zones identified (open sea, turbid flow, invariable state, hydrothermal vent field). Additionally, overlaying the near-seafloor temperature measurements on an X–Y coordinate grid generates a detailed 2D distribution of the hydrothermal vent field and clarifies the influence of fluid discharges in its formation.

Autoimmune β-cell death leads to type 1 diabetes and with findings that Ca2+-independent phospholipase A2β (iPLA2β) activation contributes to β-cell death, we assessed the effects of iPLA2β inhibition on diabetes development. Administration of FKGK18, a reversible iPLA2β inhibitor, to non-obese diabetic (NOD) mice significantly reduced diabetes incidence in association with (a) reduced insulitis, reflected by reductions in CD4+ T-cells and B-cells, (b) improved glucose homeostasis, (c) higher circulating insulin, and (d) β-cell preservation. Further, FKGK18 inhibited production of TNFα from CD4+ T-cells and antibodies from B-cells, suggesting modulation of immune cell responses by iPLA2β-derived products. Consistent with this, (a) adoptive transfer of diabetes by CD4+ T-cells to immunodeficient and diabetes-resistant NOD.scid mice was mitigated by FKGK18 pretreatment and (b) TNFα production from CD4+ T-cells was reduced by inhibitors of cyclooxygenase and 12-lipooxygenase, which metabolize arachidonic acid to generate bioactive inflammatory eicosanoids. However, adoptive transfer of diabetes was not prevented when mice were administered FKGK18-pretreated T-cells or FKGK18 administration is initiated with T-cell transfer. Our observations suggest that iPLA2β-derived lipid signals modulate immune cell responses, raising the possibility that early inhibition of iPLA2β may be beneficial in ameliorating autoimmune destruction of β-cells and mitigating type 1 diabetes development.

Proteoglycans control numerous normal and pathological processes, among which are morphogenesis, tissue repair, inflammation, vascularization and cancer metastasis. During tumor development and growth, proteoglycan expression is markedly modified in the tumor microenvironment. Altered expression of proteoglycans on tumor and stromal cell membranes affects cancer cell signaling, growth and survival, cell adhesion, migration and angiogenesis. Despite the high complexity and heterogeneity of breast cancer, the rapid evolution in our knowledge that proteoglycans are among the key players in the breast tumor microenvironment suggests their potential as pharmacological targets in this type of cancer. It has been recently suggested that pharmacological treatment may target proteoglycan metabolism, their utilization as targets for immunotherapy or their direct use as therapeutic agents. The diversity inherent in the proteoglycans that will be presented herein provides the potential for multiple layers of regulation of breast tumor behavior. This review summarizes recent developments concerning the biology of selected proteoglycans in breast cancer, and presents potential targeted therapeutic approaches based on their novel key roles in breast cancer.

Σήμερα πολλές χώρες και ιδιαίτερα η Ελλάδα πλήττονται από μια επώδυνη οικονομική κρίση. Για την υπέρβαση της κρίσης αυτής αναζητούνται κατά κύριο λόγο, εμπνευσμένοι ηγέτες οι οποίοι μεταξύ άλλων, θα άρουν και τα αδιέξοδα στα οποία έχει εγκλωβιστεί η οικονομική επιχειρηματικότητα. Οι αλλαγές που συντελούνται με επιταχυνόμενους ρυθμούς στο οικονομueικό πεδίο προκαλούν πέραν των άλλων και έναν μετασχηματισμό των χαρακτηριστικών τα οποία συνέθεταν μια εμπνευσμένη ηγεσία. Έννοιες όπως επιτυχία, καινοτομία, ηθικές πρακτικές, βιωσιμότητα και επιχειρείν επαναπροσδιορίζονται νοηματικά, γεγονός που με τη σειρά του προκαλεί την ανάγκη επανεξέτασης των τρόπων προσέγγισης και επίλυσης σύγχρονων επιχειρηματικών ζητημάτων-προβλημάτων. Σύμφωνα με τα σχετικά βιβλιογραφικά-ερευνητικά δεδομένα εμπνευσμένοι επιχειρηματίες-ηγέτες του μέλλοντος θα είναι εκείνοι που μεταξύ άλλων έχουν αναπτύξει, σε έναν υψηλό βαθμό, συναισθηματική/κοινωνική νοημοσύνη. Αυτή η εργασία εξετάζει ερευνητικά στοιχεία που  καταδεικνύουν ότι γυναίκες επιχειρηματίες χαρακτηρίζονται από την ικανότητα που έχουν να χτίζουν συναίνεση, να αναλαμβάνουν τον ρόλο του διαμεσολαβητή-ειρηνοποιού, να προσαρμόζονται ευκολότερα, να ακούν, να μοιράζονται, να δημιουργούν κίνητρα συνεργασίας και να εμπνέουν. Εμφανίζουν δηλαδή ένα υψηλό επίπεδο συναισθηματικής/κοινωνικής νοημοσύνης. Σε αυτή την προοπτική, επικεντρώνοντας το ενδιαφέρον μας στην γυναικεία επιχειρηματικότητα, τίθενται κάποια θεμελιώδη ερωτηματικά, όπως ποια είναι τα απαραίτητα στοιχεία τα οποία μπορούν να οδηγήσουν στην επαγγελματική επιτυχία. -----------------------------------------------------------------------------------------------------------------------------------Kamberidou, I. (2015). “Inspired Leaders–Empowering Leadership Skills: Women, Entrepreneurship and Sports”, pp. 28-30. Tips4skills conference, High Heels consortium, 19/2/2015, Athens, Greece [original in Greek]. In Tips4skills conference book, with support of the European Commission and the Lifelong Learning Programme of the European Union (pp. 28–30). High Heels consortium, EU project: http://www.highheelsproject.eu [Α.2.  in Apella]

 Full text:  http://www.tandfonline.com/eprint/QfxxQ5f9E7wVHtXDu7kB/full To cite this article: Irene Kamberidou (2015): Interacting, sharing and bonding: ‘notes of personal experience’ by nineteenth-century women travellers, Gender, Place & Culture: A Journal of Feminist Geography, DOI: 10.1080/0966369X.2015.1013451  To link to this article: http://dx.doi.org/10.1080/0966369X.2015.1013451

Mitochondria are highly dynamic and semi-autonomous organelles, essential for many fundamental cellular processes, including energy production, metabolite synthesis and calcium homeostasis, among others. Alterations in mitochondrial activity not only influence individual cell function but also, through non-cell autonomous mechanisms, whole body metabolism, healthspan and lifespan. Energy homeostasis is orchestrated by the complex interplay between mitochondrial biogenesis and mitochondria-selective autophagy (mitophagy). However, the cellular and molecular pathways that coordinate these 2 opposing processes remained obscure. In our recent study, we demonstrate that DCT-1, the Caenorhabditis elegans homolog of the mammalian BNIP3 and BNIP3L/NIX, is a key mediator of mitophagy, and functions in the same genetic pathway with PINK-1 and PDR-1 (the nematode homologs of PINK1 and Parkin respectively) to promote longevity and prevent cell damage under stress conditions. Interestingly, accumulation of damaged mitochondria activates SKN-1 (SKiNhead-1), the nematode homolog of NRF2, which in turn initiates a compensatory retrograde signaling response that impinges on both mitochondrial biogenesis and removal. In this commentary, we discuss the implications of these new findings in the context of innate immunity and aging. Unraveling the regulatory network that governs the crosstalk between mitochondrial biogenesis and mitophagy will enhance our understanding of the molecular mechanisms that link aberrant energy metabolism to aging and disease.

BACKGROUND & AIMS: The outcome of HBeAg-negative chronic hepatitis B virus (HBV) patients who may remain in the inactive carrier state (IC) or progress to HBeAg-negative chronic hepatitis B may be affected by the host genetic profile. Genetic polymorphisms within not only the promoter but also the coding sequence of the interferon receptor 1 (INFAR1) gene have been associated with susceptibility to chronic HBV infection, but their role on the outcomes of HBeAg-negative patients has not been evaluated. We examined the association of INFAR1 promoter polymorphisms with the phase of chronic HBV infection in a demographically characterized Caucasian cohort of 183 consecutive HBeAg-negative chronic HBV patients. METHODS: Using a combination of conventional and allele-specific polymerase chain reactions, bidirectional sequencing and DNA-fragment analysis, we performed typing of three Single Nucleotide Polymorphisms (SNPs -568G/C, -408C/T, -3C/T) and one Variable Number Tandem Repeat [VNTR -77(GT)n] within the INFR1 promoter sequence. RESULTS: The genetic polymorphisms examined were found to be associated with the phase of HBeAg-negative chronic HBV patients. Using a multiple logistic regression model adjusting for age, gender and origin of the individuals, we found that patients with linked genotypes -408CT_-3CT were more likely to be ICs (OR = 2.42 vs. CC, P = 0.036). Also, given the partial linkage between SNP -568G/C and VNTR -77(GT)n, we found that linked genotypes -77(GT)n ≤ 8/≤8_-568GC and -77(GT)n ≤ 8/≤8_-568CC were detected more frequently among ICs (OR = 11.69, P = 0.005 and OR = 7.56, P = 0.001 vs. -77(GT)n >8/>8_-568GG respectively). CONCLUSIONS: These findings suggest that these genetic variations represent important factors associated with the clinical phase of HBeAg-negative chronic HBV infection.

BACKGROUND & AIMS: The outcome of HBeAg-negative chronic hepatitis B virus (HBV) patients who may remain in the inactive carrier state (IC) or progress to HBeAg-negative chronic hepatitis B may be affected by the host genetic profile. Genetic polymorphisms within not only the promoter but also the coding sequence of the interferon receptor 1 (INFAR1) gene have been associated with susceptibility to chronic HBV infection, but their role on the outcomes of HBeAg-negative patients has not been evaluated. We examined the association of INFAR1 promoter polymorphisms with the phase of chronic HBV infection in a demographically characterized Caucasian cohort of 183 consecutive HBeAg-negative chronic HBV patients. METHODS: Using a combination of conventional and allele-specific polymerase chain reactions, bidirectional sequencing and DNA-fragment analysis, we performed typing of three Single Nucleotide Polymorphisms (SNPs -568G/C, -408C/T, -3C/T) and one Variable Number Tandem Repeat [VNTR -77(GT)n] within the INFR1 promoter sequence. RESULTS: The genetic polymorphisms examined were found to be associated with the phase of HBeAg-negative chronic HBV patients. Using a multiple logistic regression model adjusting for age, gender and origin of the individuals, we found that patients with linked genotypes -408CT_-3CT were more likely to be ICs (OR = 2.42 vs. CC, P = 0.036). Also, given the partial linkage between SNP -568G/C and VNTR -77(GT)n, we found that linked genotypes -77(GT)n 8/>8_-568GG respectively). CONCLUSIONS: These findings suggest that these genetic variations represent important factors associated with the clinical phase of HBeAg-negative chronic HBV infection.

In the 21st century technology has rapidly evolved and has managed to eliminate distances, and especially in the health sector. The purpose of this study is to investigate the families' satisfaction and effectiveness resulted from the use of telehealth services that are provided to children with diabetes mellitus type 1. The evaluation at the individual level (user) has been done by completing two questionnaires. The study involved 100 parents whose children have diabetes mellitus type 1 (50 using telemedicine and 50 without). The majority of parents involved in the study, thinks that their knowledge level on telemedicine system is sufficient (96%) and would recommend its use to other parents whose children have diabetes (82%). Meanwhile, 80% evaluate the telemedicine system as adequate.

Frataxin is a nuclear-encoded mitochondrial protein involved in the biogenesis of Fe-S-cluster-containing proteins and consequently in the functionality of the mitochondrial respiratory chain. Similar to other proteins that regulate mitochondrial respiration, severe frataxin deficiency leads to pathology in humans--Friedreich's ataxia, a life-threatening neurodegenerative disorder--and to developmental arrest in the nematode C. elegans. Interestingly, partial frataxin depletion extends C. elegans lifespan, and a similar anti-aging effect is prompted by reduced expression of other mitochondrial regulatory proteins from yeast to mammals. The beneficial adaptive responses to mild mitochondrial stress are still largely unknown and, if characterized, may suggest novel potential targets for the treatment of human mitochondria-associated, age-related disorders. Here we identify mitochondrial autophagy as an evolutionarily conserved response to frataxin silencing, and show for the first time that, similar to mammals, mitophagy is activated in C. elegans in response to mitochondrial stress in a pdr-1/Parkin-, pink-1/Pink-, and dct-1/Bnip3-dependent manner. The induction of mitophagy is part of a hypoxia-like, iron starvation response triggered upon frataxin depletion and causally involved in animal lifespan extension. We also identify non-overlapping hif-1 upstream (HIF-1-prolyl-hydroxylase) and downstream (globins) regulatory genes mediating lifespan extension upon frataxin and iron depletion. Our findings indicate that mitophagy induction is part of an adaptive iron starvation response induced as a protective mechanism against mitochondrial stress, thus suggesting novel potential therapeutic strategies for the treatment of mitochondrial-associated, age-related disorders.

{This study examined the relationship between hamstrings-to-quadriceps strength ratio (H:Q) and relative strength of the knee extensors in elite soccer players. Peak torque was measured during isokinetic knee extension/flexion at angular velocities of 60°·s-1, 180°·s-1 and 300°·s-1. 18 professional players were divided into 2 groups, depending on their H:Q at 60°·s-1. Players in the lower H:Q group (n=7) had significantly smaller H:Q ratios compared with the higher H:Q group (n=11) at all angular velocities (60°·s-1: 49.2%; 95% CI: 61.3-57.8% vs. 59.5%; 95% CI: 52.2-46.2%

{This study examined the relationship between hamstrings-to-quadriceps strength ratio (H:Q) and relative strength of the knee extensors in elite soccer players. Peak torque was measured during isokinetic knee extension/flexion at angular velocities of 60°·s-1, 180°·s-1 and 300°·s-1. 18 professional players were divided into 2 groups, depending on their H:Q at 60°·s-1. Players in the lower H:Q group (n=7) had significantly smaller H:Q ratios compared with the higher H:Q group (n=11) at all angular velocities (60°·s-1: 49.2%; 95% CI: 61.3-57.8% vs. 59.5%; 95% CI: 52.2-46.2%

Le projet d’universitarisation des études françaises en Grèce est conçu dès la fin du XIXe siècle. Il s’inscrit dans le cadre des stratégies étatiques mises en œuvre par la Grèce et la France en vue de promouvoir leurs intérêts culturels, économiques et politiques respectifs. À Thessalonique, il se concrétise par des initiatives visant, entre les deux guerres, à faire fonctionner une chaire de langue et littérature françaises au sein de la nouvelle université créée en 1925. Or, la période comprise entre la publication de la loi constitutive et la Seconde Guerre mondiale est surtout jalonnée de projets délaissés, de régressions et d’accélérations qui laissent percevoir la multiplicité des enjeux impliqués. Cependant, au cours de la décennie qui suit le conflit et sous l’effet du processus de recomposition des zones d’influence des grandes puissances, émerge en Grèce, en matière de disciplinarisation académique des littératures étrangères, un nouveau paysage universitaire composé de structures issues de conventions culturelles bilatérales : dans ce contexte, est née, en 1954, après de longues négociations menées entre les gouvernements hellénique et français, la section salonicienne d’études françaises, formule de préparation professionnelle qui, intégrée dans l’Institut de langues et littératures étrangères, devait durer jusqu’à la fin des années 1970. The project of the universitarization of French Studies in Greece has been conceived and designed since the late nineteenth century. It is part of state strategies implemented by Greece and France to promote their respective cultural, economic and political interests. In Thessaloniki, it materializes through initiatives launched during the interbellum and aiming at the creation of a Chair of French Language and Literature in the new university. However, the period between the publication in 1925 of the law establishing this University and the Second World War is mostly dotted with abandoned projects, regressions and accelerations that allow us to perceive the multiplicity and complexity of issues involved. Nevertheless, during the decade following the conflict and under the effect of the processes of recomposing the influence zones of the Great Powers, a new landscape for both Greek Schools of Humanities emerges, characterized mainly by the academic disciplinarization of Foreign Languages. It is formulated by structures stemming from bilateral cultural conventions. In this context and after lengthy negotiations between the French and the Greek government, a French Studies Department is integrated in the Institute of Foreign Languages and Literatures of Thessaloniki in 1954. This new academic formula for initial teacher professional preparation was to last until the late 1970s.

Involvement of the central nervous system (CNS) is a rare complication of multiple myeloma (MM). Herein, we have described the incidence, characteristics, prognostic factors for post CNS-MM survival, and outcome of CNS-MM and explored the efficacy of novel agents (NA) (thalidomide, bortezomib, lenalidomide) in this setting. Between 2000 and 2013, 31 (0.9 %) out of 3408 newly diagnosed symptomatic MM patients, consecutively diagnosed and treated during the same period in 12 Greek centers, developed CNS-MM (M/F 15/16, median age 59 years, range 20–96 years; newly diagnosed/relapsed-refractory 2/29; median time to CNS-MM diagnosis 29 months). Clinical and laboratory characteristics were retrospectively recorded. Twenty-six percent of patients had circulating plasma cells (PCs) or plasma cell leukemia (PCL) at CNS-MM and 39 % had skull-derived plasmacytomas, suggesting hematological and contiguous spread. Treatment for CNS-MM was offered in 29/31 patients and 11/29 responded (NA 18/29, additional radiotherapy 9/28, intrathecal chemotherapy 13/29). The median post CNS-MM survival was 3 months (95 % CI 1.9–4.1) and did not differ between patients treated with NA and/or radiotherapy vs. others. In the multivariate analysis, prior treatment of MM with NA, extramedullary disease (EMD) during MM course (i.e., plasmacytomas, circulating PCs, or documented PCL) and abnormally high LDH at MM diagnosis were independent prognostic factors, whereas treatment of CNS-MM with NA did not predict for post CNS-MM survival. Despite the relatively limited number of patients due to the rarity of CNS-MM, our results suggest that NA do not seem to improve post CNS-MM survival. Patients with EMD display shortened post CNS-MM survival and should be followed thoroughly. © 2015, Springer-Verlag Berlin Heidelberg.

Remains of past sea levels, such as tidal notches, benches, beachrocks, etc. may provide valuable information for the investigation of relative sea level changes of eustatic and/or tectonic origin. Tidal notches are usually formed in limestone cliffs in the mid-littoral zone, are well known as precise sea-level indicators and they can attest to the modality of sea level change (rapid or slow) allowing to identify palaeoseismic events. In this framework, this work focuses on the eastern coasts of the Attica Peninsula (eastern Greece) in order to trace the palaeoshorelines of the Upper Holocene through the use of tidal notches and discuss their implication for the interpretation of the recent tectonic history in the area. A submarine geomorphological investigation took place in the coasts of eastern Attica, aiming to identify palaeoshorelines. Former sea-level positions were deduced from emerged and submerged tidal notches. An attempt was made to date past sea level positions, based on 14C datings from sedimentological data of drillings in nearby locations for the submerged tidal notches while one uplifted shoreline was dated with 14C based on a shell collected at a nearby location. Eight fossil shorelines were deduced in the study area; two emerged ones at about +24±6 and +40±6 cm, and six submerged ones at about -22±6 (modern), -40±6, -60±6, -80±6, -130±6 and -460±6 cm. It is worth mentioning that a rather different tectonic behavior may be distinguished between the south (AT1-AT5) and the north (AT10-AT28) part of the study area.

À la charnière des XIXe et XXe siècles, dans un contexte de concurrence franco-allemande accrue dans l’espace balkanique, l’absence en Grèce d’une formation officielle pour francisants, vite associée au faible niveau de l’enseignement donné dans les établissements publics, fut considérée par les milieux de la diplomatie culturelle de l’Hexagone comme un obstacle notable à la promotion de la langue française. Pendant une période de trente ans, jalonnée de projets délaissés et de tentatives mort-nées, de régressions et d’accélérations, l’École française d’Athènes, établissement culturel dont l’une des missions originelles était l’enseignement, mena de difficiles négociations, officieuses et officielles, avec le gouvernement grec en vue d’être chargée de la mission de former les francisants grecs. Le projet français trouve sa réalisation en 1930 dans la loi qui créa la première structure franco-hellénique de préparation au professorat de français et confia le monopole de l’organisation des enseignements de spécialité à l’Institut supérieur d’études françaises, annexe de l’École française d’Athènes.On the verge of the twentieth century, in the midst of an ever increasing antagonism among the great powers in the Balkans, the absence in Greece of a formal instruction for teachers of French was considered by the French cultural diplomacy as a serious obstacle towards realizing the latter’s linguistic political agenda in the area. For thirty years, the French Archaeological School – a cultural institution founded in Greece in 1846 aiming, among other things, to promote the French language through Education – conducted negotiations with the Greek government in order to undertake the responsibility of professionally training Greek teachers of the French Language. This French pursuit was finally realized by the 1930 law, which created the first relevant Greek-French formation structure and assigned the monopoly of organizing specialization courses to the educational branch of the French Archaeological School, the French Institute.

Le but de l’article est de décrire une expérience éducative réalisée en contexte universitaire, afin de discuter de la contribution du tutorat par les pairs au développement de la compétence pédagogique des futurs et novices enseignants de FLE. L’étude de cas en question a duré tout au long d’un semestre académique et a impliqué des étudiants du 1er et du 2e cycle.

The dorsiventral, hypostomatic leaf of Euphorbia characias is investigated to disclose its structural features and the chemical nature of the secondary metabolites produced. Light and scanning electron microscopy along with histochemical tests were employed to investigate the leaf of this well known perennial dwarf Mediterranean shrub. The compact leaf is characterized by numerous, rather uniform, curly, unicellular hairs on both surfaces, vaulty protrusions of the outer periclinal walls of the epidermal cells, prominent on the lower epidermis in particular, and a network of latex producing ducts (laticifers) extending in two layers within the mesophyll. Histochemical reactions proved positive only for alkaloids within the laticifers and phenolic compounds, especially for the condensed tannins accumulated within the vacuole of the epidermal cells. GC-MS and GC-FID analyses of the latex revealed the presence of several secondary metabolites, mainly belonging to the class of triterpenes. Lanosterol, butyrospermol, cycloartenol and lupeol were the major constituents in the extract examined. © 2014 Elsevier GmbH.

Biomechanical findings show that running is asymmetric in many kinetic properties. Running stiffness is a vital kinetic property of yet unknown pattern of lateralization. The aim of this study was to examine the degree and variability of lower limb dominance specific asymmetry of running in terms of leg stiffness, vertical stiffness, contact time, flight time, maximal ground reaction forceduring contact, vertical displacement of the center of mass, and change in leg length. Leg and vertical stiffness was estimated by the sine-wave method in 22 young males during treadmill runningat 4.44m/s. Lower limb dominance was determined by the triple jump test. Asymmetry was expressed as dominant – non-dominant, and indexed by the absolute asymmetry index. Significant asymmetry was found only in flight time (3.98%) and in maximal ground reaction force (1.75%). The absolute asymmetry index ranged from 1.8% to 6.4%, showed high variation between subjects (0–31.6%), and differentiated among the 7 analyzed variables. Leg and vertical stiffness in treadmill running of moderate pace (4.44 m/s) should be considered symmetric.

This is the first of a two-volume final report on the excavation of the Minoan cemetery and associated finds at Livari Skiadi, near Goudouras, at the southeastern end of Crete. The cemetery was unearthed during a rescue excavation performed by the 24th Ephorate of Prehistoric and Classical Antiquities of the Hellenic Ministry of Culture, under the direction of Chrysa Sofianou, who was at that time responsible for the antiquities of the Siteia prefecture, and with the participation of Yiannis Papadatos, together with a small group of archaeology students from the Department of History and Archaeology of the National and Kapodistrian University of Athens. The excavation lasted three consecutive summers, from 2008 until 2010, and it revealed a tholos tomb and burial rock shelter used in the Prepalatial period, a house tomb dated to the Neopalatial period, and deposits of funerary material in open areas surrounding these tombs.

Bortezomib and lenalidomide are increasingly used in patients with AL amyloidosis, but long term data on their use as primary therapy in AL amyloidosis are lacking while early mortality remains significant. Thus, we analyzed the long term outcomes of 85 consecutive unselected patients, which received primary therapy with bortezomib or lenalidomide and we prospectively evaluated a risk adapted strategy based on bortezomib/dexamethasone to reduce early mortality. Twenty-six patients received full-dose bortezomib/dexamethasone, 36 patients lenalidomide with oral cyclophosphamide and low-dose dexamethasone and 23 patients received bortezomib/dexamethasone at a dose and schedule adjusted to the risk of early death. On intent to treat, 67% of patients achieved a hematologic response (24% hemCRs) and 34% an organ response; both were more frequent with bortezomib. An early death occurred in 20%: in 36% of those treated with full-dose bortezomib/dexamethasone, in 22% of lenalidomide-treated patients but only in 4.5% of patients treated with risk-adapted bortezomib/dexamethasone. Activity of full vs. adjusted dose bortezomib/dexamethasone was similar; twice weekly vs. weekly administration of bortezomib also had similar activity. After a median follow up of 57 months, median survival is 47 months and is similar for patients treated with bortezomib vs. lenalidomide-based regimens. However, risk adjusted-bortezomib/dexamethasone was associated with improved 1-year survival vs. full-dose bortezomib/dexamethasone or lenalidomide-based therapy (81% vs. 56% vs. 53%, respectively). In conclusion, risk-adapted bortezomib/dexamethasone may reduce early mortality and preserve activity while long term follow up indicates that remissions obtained with lenalidomide or bortezomib may be durable, even without consolidation with alkylators. © 2015 Wiley Periodicals, Inc.

Consecutive patients that had primary metal-on-metal (MoM) or metal-on-polyethylene (MoP) hip arthroplasty were prospectively enrolled to this study. All operated hips were evaluated with MRI by one radiologist who was blinded to the radiographic findings and clinical symptoms. Three groups of patients were formed: (1) thirteen MoM THRs in 13 patients with groin pain (Group 1), (2) ten MoM THRs in 10 patients with no pain (Group 2), (3) five MoP THRs in 4 patients without pain (control group). Abnormal MRI findings were distributed in all groups in a balanced way, irrespective of the patients' symptoms, prostheses, or metal ion levels. Two patients from Group 1 and one patient of Group 3 (control group) were diagnosed with a large periprosthetic mass (pseudotumor).

Multiciliated cells are abundant in the epithelial surface of different tissues, including cells lining the walls of the lateral ventricles in the brain and the airway epithelium. Their main role is to control fluid flow and defects in their differentiation are implicated in many human disorders, such as hydrocephalus, accompanied by defects in adult neurogenesis and mucociliary disorder in the airway system. Here we show that Mcidas, which is mutated in human mucociliary clearance disorder, and GemC1 (Gmnc or Lynkeas), previously implicated in cell cycle progression, are key regulators of multiciliated ependymal cell generation in the mouse brain. Overexpression and knockdown experiments show that Mcidas and GemC1 are sufficient and necessary for cell fate commitment and differentiation of radial glial cells to multiciliated ependymal cells. Furthermore, we show that GemC1 and Mcidas operate in hierarchical order, upstream of Foxj1 and c-Myb transcription factors, which are known regulators of ependymal cell generation, and that Notch signaling inhibits GemC1 and Mcidas function. Our results suggest that Mcidas and GemC1 are key players in the generation of multiciliated ependymal cells of the adult neurogenic niche.

Spin periods of Be/X-ray binary (BeXRB) pulsars are important for probing their formation channels and the connection between orbital period and pulsar spin in XRBs (Knigge+ 2011). From the 120 BeXRBs in the SMC only 50% have known spin periods, with the majority of them measured during outburst with ToOs. From the remaining systems only 6 have a known orbital period. XMMU J004855.5-734946 is a BeXRB in the SMC (Haberl & Sturm 2016, XMM Lx (0.03-1)x10^35 erg/s) with a 36.43d orbital period (Atel#9198), but with no X-ray pulsations detected so far. On 06/24 a 37s Swift/XRT observation detected the system at Lx 10^37 erg/s (Atel#9197) following a marginal detection on 06/16 (Lx<5x10^36 erg/s) confirming the onset of a large outburst. A follow-up 1ks Swift ToO on 06/29 measures an Lx = 8.3x10^36 erg/s. This is a unique opportunity to measure the spin period of one of the few BeXRBs in the SMC with known orbital period but unknown spin period.

The assessment of dietary attitudes and behaviors provides information of interest to sports nutritionists. Although there has been little analysis of the quality of research undertaken in this field, there is evidence of a number of flaws and methodological concerns in some of the studies in the available literature. This review undertook a systematic assessment of the attributes of research assessing the nutritional knowledge and attitudes of athletes and coaches. Sixty questionnaire-based studies were identified by a search of official databases using specific key terms with subsequent analysis by certain inclusion–exclusion criteria. These studies were then analyzed using 33 research quality criteria related to the methods, questionnaires, and statistics used. We found that many studies did not provide information on critical issues such as research hypotheses (92%), the gaining of ethics approval (50%) or informed consent (35%), or acknowledgment of limitations in the implementation of studies or interpretation of data (72%). Many of the samples were non-probabilistic (85%) and rather small (42%). Many questionnaires were of unknown origin (30%), validity (72%), and reliability (70%) and resulted in low (≤ 60%) response rates (38%). Pilot testing was not undertaken in 67% of the studies. Few studies dealt with sample size (2%), power (3%), assumptions (7%), confidence intervals (3%), or effect sizes (3%). Improving some of these problems and deficits may enhance future research in this field.

In the case of pediatric medicinal products the selection of an appropriate and palatable liquid dosage form can make the difference between treatment success and failure. Since the recent adoption of Pediatric Regulations in the U.S. and E.U., there is a greater demand for age-appropriate medicines for children. Extended research on the use of milk on drug administration in pediatric population has shown the multiple benefits of its use. Milk exhibits great solubilizing, gastroprotective and taste masking properties, which are very important characteristics in the case of insoluble, irritating and bitter-tasting active compounds. Milk-based formulations rely on a novel, simple and user-friendly approach for the delivery of ionized and unionized lipophilic drugs. In parallel they can provide critical nutritive elements and a wide range of biologically active peptides, very important elements especially for pediatric patients. (C) 2015 Elsevier B.V. All rights reserved.

This paper addresses the critical issue of how wrong can water resources management go if the structure and hydrodynamic evolution of the exploited system is not well known. As a case study the River Pinios estuarine groundwater system in central Greece, is discussed. The study area has a spatial extent of about 80km2 and a typical estuarine shape. Due to the neotectonic evolution and the eustatic moves, a unique geomorphological environment and a dense hydrological network have been developed. Dominant socioeconomic activity in the region is agriculture and secondarily tourism that is focused only along a narrow strip along the coastal line and occurs only seasonally. Domestic water demands are covered by groundwater abstractions mainly from deeper wells drilled at the margins of the estuarine. Shallow wells in the alluvial sediments of the basin augment irrigation demands that are predominantly catered by surface water from the river Pinios and its tributaries, and to a minor extent several springs that emerge along the marginal fans of the basin. Due to the shallow groundwater levels, a large percentage of irrigation demands is covered by direct osmosis of water from the root zone.

Mitochondria represent the major bioenergetic hub coordinating cellular and organismal homeostasis. The underlying causes of many pathologies tormenting humans converge on impaired mitochondrial maintenance. Mitochondria-specific autophagy (mitophagy), a cellular catabolic process targeting mitochondria, holds a prominent role in mitochondrial quality control. In addition to core autophagic machinery components, mitophagy exploits a variety of molecules that identify damaged or superfluous mitochondria and mediate their elimination. Signaling pathways integrating environmental and genetic stimuli interact with key mitophagy effectors to activate cellular stress response mechanisms, ultimately modulating health and lifespan. Here, we review the signaling cascades and molecular mechanisms that govern the process of mitophagy and discuss their involvement in ageing and neurodegeneration. This article is part of a Special Issue entitled: Mitochondrial Dysfunction in Aging.

Molecular typing data on antimicrobial-resistant Propionibacterium strains are limited in the literature. We examined antimicrobial resistance profiles and the underlying resistance mechanisms in Propionibacterium spp. isolates recovered from patients with moderate to severe acne vulgaris in Greece. The clonallity of the resistant Propionibacterium acnes isolates was also investigated. Propionibacterium spp. isolates were detected using Tryptone-Yeast Extract-Glucose (TYG) agar plates supplemented with 4% furazolidone. Erythromycin, clindamycin, vancomycin, penicillin, co-trimoxazole, doxycycline, minocycline and ciprofloxacin MICs were determined using the gradient strip method. Erythromycin, clindamycin and tetracycline mechanisms of resistance were determined using PCR and sequencing of the domain V of 23S rRNA and 16S rRNA, as well as the presence of the ermX gene. Typing was performed using the multi locus sequence typing (MLST) methodology. Seventy nine isolates from 76 patients were collected. Twenty-three isolates (29.1%) exhibited resistance to erythromycin and clindamycin, while two additional isolates (2.5%) were resistant only to erythromycin. Resistance to tetracycline was not detected. The underlying molecular mechanisms were point mutations A2059G and A2058G. MLST typing of the P. acnes resistant isolates revealed that lineage type IA1 (ST-1, 3 and 52) prevailed (12/18; 66.7%), whilst lineage type IA2 (ST-2 and 22) accounted for five more isolates (27.8%). Susceptible isolates were more evenly distributed between ST types. Propionibacterium spp. from moderate to severe acne vulgaris in Greece are frequently resistant to erythromycin/clindamycin but not to tetracyclines, mainly due to the point mutations A2059G and A2058G. P. acnes resistant isolates were more clonally related than susceptible ones and belonged to a limited number of MLST types.

BACKGROUND: HIV-1 subtype B is the predominant one in European regions several, while other subtypes and recombinants are also circulating with high prevalence. A sub-epidemic of subtype F with specific characteristics and low response to treatment has been recently identified in Galicia. In this study we investigated the characteristics of the HIV-1 subtype F sub-epidemic in A Coruña and Santiago de Compostela in Northwest Spain. METHODS: 420 newly HIV-1 diagnosed patients during 2009-2013 were enrolled in this study. HIV-1 subtyping was carried out using automated subtyping tools and phylogenetic analysis. Molecular epidemiology investigation of subtypes B and F was performed by means of phylogenetic analysis using fast maximum likelihood. Phylodynamic analysis was performed using Bayesian method as implemented in BEAST v1.8. RESULTS: Subtype B found to be the predominant (61.2% and 70.4%) followed by subtype F (25.6% and 12.0%) in both areas (A Coruña and Santiago de Compostela, respectively). The latter found to mainly spread among men having sex with men (MSM). The vast majority of subtype F lineages from both areas clustered monophyletically, while subtype B sequences clustered in several tree branches. The exponential growth of subtype F sub-epidemic dated back in 2008 by means of phylodynamic analysis. Most of new infections during 2009-2013 occurred within the subtype F transmission cluster. CONCLUSIONS: Subtype F circulates at high prevalence in A Coruña and Santiago de Compostela in Northwest Spain, suggesting that the HIV-1 epidemic in this region has distinct characteristics to the rest of Spain. Subtype F has being spreading among MSM and is currently the most actively spreading network. The single cluster spread of this local sub-epidemic might provide an explanation for the distinct characteristics and the low response to antiretroviral treatment.

Through the eyes of western women of the 18th and 19th centuries, this paper discusses the Ottoman slavery institution and 'the real position of women in the religious system of Islam' (Garnett 1895: 61).  Focusing on primary sources, first-hand accounts of European women travel writers, authors and journalists in Ottoman territories and principally in Asia Minor (Turkey), this article confirms that all the harem inmates were women of different nations and races: Islamized slaves, liberated slaves and descendants of slaves. Western women, in their intimate contacts with the harem inmates—free and slave—discuss the Ottoman dynasty’s reproductive politics, forced abortion, marriage, divorce, veiling or Muslim women’s attire,  slave rights and social mobility, including requirements for slave liberation. This researcher concludes that the Multiethnic-Multiracial Harem Slavery Institution was the collective segregation, confinement or enslavement of the female gender in one specific space (household/harem), as one collective identity since all the women—slave and free—shared or legally belonged to one man or master: sultan, grand vizier, vizier, pacha, etc. Keywords: slavery, sexual slavery, social mobility, polygyny, eunuchs, children’s harem, seraglio, marriage, divorce, veiling ----------------------------------------------------------------------------------------------- When citing: Kamberidou, I. (2015). The Multiethnic Slavery Institution through the Eyes of Western Women and 'the real position of women in the religious system of Islam'. In Miriam Diez Bosch and Jordi Sanchez Torrents (eds). Media, Religion and Gender in Europe (pp. 53-79). Barcelona: Blanquerna Observatory on Media, Religion and Culture. Faculta de Comunicatio i Relacions Internacionals Blanquerna,Universitat Ramon Llull.  DOI: 10.13140/RG.2.1.3034.4166 ·

This chapter has shown that the multiethnic harem slavery institution was the Ottoman system’s primary socialization agent and an indispensable part of its self­-reproduction. It has contributed to the discourse on sexual slavery, primarily through the first-hand accounts of western women and harem inmates of the 19th century. It has shown that multiethnic–multiracial slavery was vital for the Ottoman economy and social system and provided a means of social integration-assimilation and social mobility: status and political power. Sexual slavery was a central part of the slave system and slaves of both genders were easily integrated into Ottoman society, eventually becoming free Muslims.       Mainly through the eyes of western women and harem inmates of the 19th century, corroborating that the harem system was based on slavery, this chapter has contributed additional evidence confirming that:  firstly, the expansionist views of Islam and the institution of slavery resulted in the multiethnic composition of the Ottoman households: harems and selemliks. Secondly, an Ottoman harem— especially that of the elite and so-called middle-class—was made up of women and children from different nations: Islamized slaves, liberated slaves and descendants of slaves, including islamized eunuchs. Thirdly, the Ottoman elite was responsible for the preservation of slavery until the early 20th century and, as a result, the prolongation of polygyny and the large-scale castration of African boys, which was another dehumanizing aspect of the Ottoman slavery institution.   Acknowledgments I would like to express my gratitude to the Greek artist Areti Kamperidis for her magnificent artwork, including her exceptional paintings, inspired by the female accounts and illustrated in this article.Keywords: human trafficking, slavery, sexual slavery, social mobility, polygyny, eunuchs, children’s harem, seraglio, marriage, divorce, veiling, gender, womenWHEN CITING: Kamberidou, I. (2015). The Multiethnic Slavery Institution through the Eyes of Western Women and 'the real position of women in the religious system of Islam'. In Miriam Diez Bosch and Jordi Sanchez Torrents (eds). Media, Religion and Gender in Europe (pp. 53-79). Barcelona: Blanquerna Observatory on Media, Religion and Culture. Faculta de Comunicatio i Relacions Internacionals Blanquerna,Universitat Ramon Llull.                     [Α.1. in Apella]    

Tidal notches are a well-known sea-level indicator, marking clearly former shorelines, which have often been used to deduce Quaternary tectonic trends and sea-level changes, mainly in uplifting areas. If raised notches have often been used to estimate past changes in sea level and tectonic movements, submerged notches, which are more difficult to observe, have been studied mainly occasionally by a few authors. Nevertheless, Holocene tectonics may include more than a single episode and it may be useful to extend underwater observations below the first submerged notch. In this context, this work focuses in the Aegean region, an area characterized by extensional tectonics, where subsidence prevails, related to the subduction of the Mediterranean floor below the Hellenic arc, where Quaternary uplift trends tend to prevail. In some islands of Cyclades and Sporades, there is evidence of the occurrence of repeated rapid subsidences during the Late Holocene. In this paper, the shape of tidal notches that may well be preserved underwater is recalled in order to reconstruct sequences of coseismic subsidences and other relative sea-level changes that occurred during at least the last few millennia. A re-analysis of already published measurements of submerged tidal notches in several islands reveals that subsidence trends in many areas of the Aegean are not continuous and gradual, but the result of repeated coseismic vertical subsidences of some decimetres at each time. The estimated average return times are of the order of approximately some centuries to one millennium. Although the results cannot be used for short-term predictions of earthquakes, they may provide useful indications about the long-term tectonic trends that are active in the Aegean region.

Muscle LIM Protein (MLP) has emerged as a key regulator of striated muscle physiology and pathophysiology. Mutations in cysteine and glycine-rich protein 3 (CSRP3), the gene encoding MLP, are causative of human cardiomyopathies, whereas altered expression patterns are observed in human failing heart and skeletal myopathies. In vitro and in vivo evidences reveal a complex and diverse functional role of MLP in striated muscle, which is determined by its multiple interacting partners and subcellular distribution. Experimental evidence suggests that MLP is implicated in both myogenic differentiation and myocyte cytoarchitecture, although the full spectrum of its intracellular roles still unfolds.

The aim of the study was to compare the effects of compound vs. complex resistance training on strength, high-speed movement performance, and muscle composition. Eighteen young men completed compound (strength and power sessions on alternate days) or complex training (strength and power sets within a single session) 3 times per week for 6 weeks using bench press, leg press, Smith machine box squat, and jumping exercises. Pre- and posttraining, jumping and throwing performance and maximum bench press, leg press, and Smith machine box squat strength were evaluated. The architecture of vastus lateralis and gastrocnemius muscle was assessed using ultrasound imaging. Vastus lateralis morphology was assessed from muscle biopsies. Jumping (4 ± 3%) and throwing (9 ± 8%) performance increased only with compound training (p < 0.02). Bench press (5 vs. 18%), leg press (17 vs. 28%), and Smith machine box squat (27 vs. 35%) strength increased after both compound and complex training. Vastus lateralis thickness and fascicle angle and gastrocnemius fascicle angle were increased with both compound and complex training. Gastrocnemius fascicle length decreased only after complex training (-11.8 ± 9.4%, p = 0.006). Muscle fiber cross-sectional areas increased only after complex training (p ≤ 0.05). Fiber type composition was not affected by either intervention. These results suggest that short-term strength and power training on alternate days is more effective for enhancing lower-limb and whole-body power, whereas training on the same day may induce greater increases in strength and fiber hypertrophy.

BACKGROUND: There is sparse evidence that demonstrates the association between macro-environmental processes and drug-related HIV epidemics. The present study explores the relationship between economic, socio-economic, policy and structural indicators, and increases in reported HIV infections among people who inject drugs (PWID) in the European Economic Area (EEA). METHODS: We used panel data (2003-2012) for 30 EEA countries. Statistical analyses included logistic regression models. The dependent variable was taking value 1 if there was an outbreak (significant increase in the national rate of HIV diagnoses in PWID) and 0 otherwise. Explanatory variables included the growth rate of Gross Domestic Product (GDP), the share of the population that is at risk for poverty, the unemployment rate, the Eurostat S80/S20 ratio, the Gini coefficient, the per capita government expenditure on health and social protection, and variables on drug control policy and drug-using population sizes. Lags of one to three years were investigated. FINDINGS: In multivariable analyses, using two-year lagged values, we found that a 1% increase of GDP was associated with approximately 30% reduction in the odds of an HIV outbreak. In GDP-adjusted analyses with three-year lagged values, the effect of the national income inequality on the likelihood of an HIV outbreak was significant [S80/S20 Odds Ratio (OR) = 3.89; 95% Confidence Interval (CI): 1.15 to 13.13]. Generally, the multivariable analyses produced similar results across three time lags tested. INTERPRETATION: Given the limitations of ecological research, we found that declining economic growth and increasing national income inequality were associated with an elevated probability of a large increase in the number of HIV diagnoses among PWID in EEA countries during the last decade. HIV prevention may be more effective if developed within national and European-level policy contexts that promote income equality, especially among vulnerable groups.

BACKGROUND: There is sparse evidence that demonstrates the association between macro-environmental processes and drug-related HIV epidemics. The present study explores the relationship between economic, socio-economic, policy and structural indicators, and increases in reported HIV infections among people who inject drugs (PWID) in the European Economic Area (EEA). METHODS: We used panel data (2003-2012) for 30 EEA countries. Statistical analyses included logistic regression models. The dependent variable was taking value 1 if there was an outbreak (significant increase in the national rate of HIV diagnoses in PWID) and 0 otherwise. Explanatory variables included the growth rate of Gross Domestic Product (GDP), the share of the population that is at risk for poverty, the unemployment rate, the Eurostat S80/S20 ratio, the Gini coefficient, the per capita government expenditure on health and social protection, and variables on drug control policy and drug-using population sizes. Lags of one to three years were investigated. FINDINGS: In multivariable analyses, using two-year lagged values, we found that a 1% increase of GDP was associated with approximately 30% reduction in the odds of an HIV outbreak. In GDP-adjusted analyses with three-year lagged values, the effect of the national income inequality on the likelihood of an HIV outbreak was significant [S80/S20 Odds Ratio (OR) = 3.89; 95% Confidence Interval (CI): 1.15 to 13.13]. Generally, the multivariable analyses produced similar results across three time lags tested. INTERPRETATION: Given the limitations of ecological research, we found that declining economic growth and increasing national income inequality were associated with an elevated probability of a large increase in the number of HIV diagnoses among PWID in EEA countries during the last decade. HIV prevention may be more effective if developed within national and European-level policy contexts that promote income equality, especially among vulnerable groups.

BACKGROUND: Greece experienced an unprecedented increase in HIV cases among drug injectors in 2011 after economic crisis. Network-level factors are increasingly understood to drive HIV transmission in emerging epidemics. METHODS: We examined the relationship between networks, risk behaviors, and HIV serostatus among 1404 people who inject drugs in Athens, Greece. We generated networks using the chain-referral structure within a large HIV screening program. Network proportions, the proportion of a respondent's network with a given characteristic, were calculated. Multiple logistic regression models were used to assess the relationship between network proportions and individual HIV seroprevalence, injection frequency and unprotected sex. RESULTS: Of note, 1030 networks were generated. Respondent HIV seroprevalence was associated with greater proportions of network members who were HIV infected (ie, those with ≥ 50% of network members HIV positive vs. those with no network members HIV positive) (AOR: 3.11; 95% CI: 2.10 to 4.62), divided drugs (AOR: 1.60; 95% CI: 1.10 to 2.35), or injected frequently (AOR: 1.50; 95% CI: 1.02 to 2.21). Homelessness was the only sociodemographic characteristic associated with a risk outcome measure--high-frequency injecting (AOR: 1.41; 95% CI: 1.03 to 1.93). These associations were weaker for more distal second- and third-degree networks and not present when examined within random networks. CONCLUSIONS: Networks are an independently important contributor to the HIV outbreak in Athens, Greece. Network associations were strongest for the immediate network, with residual associations for distal networks. Homelessness was associated with high-frequency injecting. Prevention programs should consider including network-level interventions to prevent future emerging epidemics.

BACKGROUND: Greece experienced an unprecedented increase in HIV cases among drug injectors in 2011 after economic crisis. Network-level factors are increasingly understood to drive HIV transmission in emerging epidemics. METHODS: We examined the relationship between networks, risk behaviors, and HIV serostatus among 1404 people who inject drugs in Athens, Greece. We generated networks using the chain-referral structure within a large HIV screening program. Network proportions, the proportion of a respondent's network with a given characteristic, were calculated. Multiple logistic regression models were used to assess the relationship between network proportions and individual HIV seroprevalence, injection frequency and unprotected sex. RESULTS: Of note, 1030 networks were generated. Respondent HIV seroprevalence was associated with greater proportions of network members who were HIV infected (ie, those with >/= 50% of network members HIV positive vs. those with no network members HIV positive) (AOR: 3.11; 95% CI: 2.10 to 4.62), divided drugs (AOR: 1.60; 95% CI: 1.10 to 2.35), or injected frequently (AOR: 1.50; 95% CI: 1.02 to 2.21). Homelessness was the only sociodemographic characteristic associated with a risk outcome measure--high-frequency injecting (AOR: 1.41; 95% CI: 1.03 to 1.93). These associations were weaker for more distal second- and third-degree networks and not present when examined within random networks. CONCLUSIONS: Networks are an independently important contributor to the HIV outbreak in Athens, Greece. Network associations were strongest for the immediate network, with residual associations for distal networks. Homelessness was associated with high-frequency injecting. Prevention programs should consider including network-level interventions to prevent future emerging epidemics.

The purpose of our study was to summarize all the knowledge concerning the innovative pioneer in the field of orthopaedic surgery, Nicholas J. Giannestras (1908-1978). A thorough study of texts, medical books and reports, in the field of history of medicine, together with a review of the available literature in PubMed, was undertaken. Giannestras left his mark in the history of orthopaedics with his clinical work and his publications, mainly his treatise "Foot Disorders: Medical and Surgical Management" (1973), while his name lingers in Greece with the introduction of spine fusion with the use of metallic implants. He was an eminent university clinical professor of orthopaedics who had harmonically combined academic writing, teaching and clinical research in every field of orthopaedic surgery.

BACKGROUND: Age-related macular degeneration (AMD) is a degenerative ocular disease, which may lead to loss of central vision. In Caucasian populations, a strong correlation has been established with polymorphism Y402H (rs1061170) in the complement factor H gene (CFH). The H131R polymorphism (rs1801274) in the FCGR2A gene has been associated with many inflammatory diseases, but has not been investigated in relation to AMD. The goal of our study was the development of a novel method for Y402H (g.43097C>T) genotyping, the confirmation of its association with AMD in the Greek population and the investigation of the H131R polymorphism in AMD. METHODS: DNAs were extracted from blood samples of 120 patients with the severe wet form of AMD and 103 age- and sex-matched controls, all of whom were clinically evaluated. A real-time PCR and melting curve analysis method for Y402H genotyping was developed in the LightCycler platform, after in silico design of appropriate primers and probes. Genotyping for H131R was performed using a real-time PCR method previously described by our group. RESULTS: The novel genotyping method for Y402H in the CFH gene is fast, reproducible (Efficiency=1.79, reproducibility CVCq=3.33%, Tm C allele 53.36 degrees C and T allele 61.91 degrees C, DeltaTm=8.55) and accurate as results were confirmed with the gold standard DNA Sequencing method. CONCLUSIONS: The present study confirmed the association between CFH Y402H SNP and wet AMD in the Greek population (OR=1.77, p=0.002). FCGR2A H131R polymorphism was investigated for the first time in this present study for possible correlation with wet AMD and a statistically significant association was detected (OR=1.74, p=0.006), that awaits further confirmation in a larger set of samples

OBJECTIVES: Chewing efficiency may be evaluated using cohesive specimen, especially in elderly or dysphagic patients. The aim of this study was to evaluate three two-coloured chewing gums for a colour-mixing ability test and to validate a new purpose built software (ViewGum©). METHODS: Dentate participants (dentate-group) and edentulous patients with mandibular two-implant overdentures (IOD-group) were recruited. First, the dentate-group chewed three different types of two-coloured gum (gum1-gum3) for 5, 10, 20, 30 and 50 chewing cycles. Subsequently the number of chewing cycles with the highest intra- and inter-rater agreement was determined visually by applying a scale (SA) and opto-electronically (ViewGum©, Bland-Altman analysis). The ViewGum© software determines semi-automatically the variance of hue (VOH); inadequate mixing presents with larger VOH than complete mixing. Secondly, the dentate-group and the IOD-group were compared. RESULTS: The dentate-group comprised 20 participants (10 female, 30.3±6.7 years); the IOD-group 15 participants (10 female, 74.6±8.3 years). Intra-rater and inter-rater agreement (SA) was very high at 20 chewing cycles (95.00-98.75%). Gums 1-3 showed different colour-mixing characteristics as a function of chewing cycles, gum1 showed a logarithmic association; gum2 and gum3 demonstrated more linear behaviours. However, the number of chewing cycles could be predicted in all specimens from VOH (all p<0.0001, mixed linear regression models). Both analyses proved discriminative to the dental state. CONCLUSION: ViewGum© proved to be a reliable and discriminative tool to opto-electronically assess chewing efficiency, given an elastic specimen is chewed for 20 cycles and could be recommended for the evaluation of chewing efficiency in a clinical and research setting. CLINICAL SIGNIFICANCE: Chewing is a complex function of the oro-facial structures and the central nervous system. The application of the proposed assessments of the chewing function in geriatrics or special care dentistry could help visualising oro-functional or dental comorbidities in dysphagic patients or those suffering from protein-energy malnutrition.

Valid characterization of carotid atherosclerosis (CA) is a crucial public health issue, which would limit the major risks held by CA for both patient safety and state economies. This paper investigated the unexplored potential of kinematic features in assisting the diagnostic decision for CA in the framework of a computer-aided diagnosis (CAD) tool. To this end, 15 CAD schemes were designed and were fed with a wide variety of kinematic features of the atherosclerotic plaque and the arterial wall adjacent to the plaque for 56 patients from two different hospitals. The CAD schemes were benchmarked in terms of their ability to discriminate between symptomatic and asymptomatic patients and the combination of the Fisher discriminant ratio, as a feature-selection strategy, and support vector machines, in the classification module, was revealed as the optimal motion-based CAD tool. The particular CAD tool was evaluated with several cross-validation strategies and yielded higher than 88% classification accuracy; the texture-based CAD performance in the same dataset was 80%. The incorporation of kinematic features of the arterial wall in CAD seems to have a particularly favorable impact on the performance of image-data-driven diagnosis for CA, which remains to be further elucidated in future prospective studies on large datasets.

abstract extra virgin olive oil contains significant quantities of polar phenolic ingredients. The large majority is made up of esters of tyrosol or hydroxytyrosol with secoiridoid derivatives from oleuropein or ligstroside. in the current study we describe a number of new or incompletely characterized forms of ligstroside and oleuropein aglycons. two of them which are stable enolic forms are described for the first time as real olive oil ingredients although their presence in olive oil had been postulated. to minimize the confusion with the complicated names of the agly-con isomers we propose the names oleokoronal and oleomissional for the two ingredients. after screening 2000 samples of olive oil from most major varieties we were able to identify samples of olive oil in which oleokoronal and oleomissional were the major phenolic ingredients and could be used as starting material for their isolation. interestingly, during normal or reversed phase chromatography both compounds were transformed to the known forms of monoaldehydic closed ring aglycons, which offers an explanation as to why those compounds had not been identified so far. Their real presence in olive oil was confirmed by direct nMr observation without the use of any solvent.

abstract extra virgin olive oil contains significant quantities of polar phenolic ingredients. The large majority is made up of esters of tyrosol or hydroxytyrosol with secoiridoid derivatives from oleuropein or ligstroside. in the current study we describe a number of new or incompletely characterized forms of ligstroside and oleuropein aglycons. two of them which are stable enolic forms are described for the first time as real olive oil ingredients although their presence in olive oil had been postulated. to minimize the confusion with the complicated names of the agly-con isomers we propose the names oleokoronal and oleomissional for the two ingredients. after screening 2000 samples of olive oil from most major varieties we were able to identify samples of olive oil in which oleokoronal and oleomissional were the major phenolic ingredients and could be used as starting material for their isolation. interestingly, during normal or reversed phase chromatography both compounds were transformed to the known forms of monoaldehydic closed ring aglycons, which offers an explanation as to why those compounds had not been identified so far. Their real presence in olive oil was confirmed by direct nMr observation without the use of any solvent.

Central to the process of transmembrane cargo trafficking is the successful folding and exit from the ER through packaging in COPII vesicles. Here, we use the UapA purine transporter of Aspergillus nidulans to investigate the role of cargo oligomerization in membrane trafficking. We show that UapA oligomerizes (at least dimerizes) and that oligomerization persists upon UapA endocytosis and vacuolar sorting. Using a validated BiFC assay, we provide evidence that a UapA oligomerization is associated with ER exit and turnover, as ER-retained mutants, either due to modification of a Tyr-based N-terminal motif or partial misfolding, physically associate, but do not associate properly. Co-expression of ER-retained mutants with wild-type UapA leads to in trans plasma membrane localization of the former, confirming that oligomerization initiates in the ER. Genetic suppression of an N-terminal mutation in the Tyr motif and mutational analysis suggest that transmembrane α-helix 7 affects the oligomerization interface. Our results reveal that transporter oligomerization is essential for membrane trafficking and turnover and is a common theme in fungi and mammalian cells.

BACKGROUND: Atherosclerotic lesions at the origin of common carotid, subclavian, and innominate arteries are causes for brain and hand ischemic symptoms. Surgical reconstructions of symptomatic cases remain the golden standard treatment, although the endovascular approach has been promising as well. In this retrospective study, long-term results of open reconstructions from 2 University Hospitals are presented. METHODS: Through a 30-year period, prospective data of 107 patients, suffering from symptomatic atherosclerotic supra-aortic artery disease, were retrospectively reviewed and included in this study. Demographic data, arterial risk factors, presenting symptoms and signs, diagnostic evaluation, operative treatment and complications, resolution of symptoms, redo surgery, and overall mortality were analyzed. RESULTS: Eighty-one patients were operated on for subclavian, 14 for innominate, and 12 for common carotid severe lesions, through an extra-thoracic reconstruction (91 patients) or a transthoracic one (16 patients). Perioperative mortality was null although morbidity was 16.8%, and primary perioperative patency was 97.2% (secondary patency 100%). The cumulative primary patency was 95.3%, 90.7%, and 86.0% at 5, 10, and 15 years, respectively. The mean time of patency was 214.6 months (95% confidence interval = 198.5-230.6), with no difference between transthoracic and extrathoracic reconstructions (P = 0.278). CONCLUSIONS: Open reconstructions remain a therapeutic strategy with a considerably low perioperative morbidity/mortality offering excellent long-term results regarding patency of the reconstructions and clinical resolution of the symptoms. However, in the modern era of the endovascular techniques, we need more studies for establishing anatomic and clinical criteria regarding patient selection for endovascular angioplasty/stenting or open repair.

V404 Cyg is a known black hole Low mass X-ray binary with a late G-type companion, having a ~6.5 d orbital period. On June 15 18:32 UT Swift Burst Alert Telescope (BAT) was triggered due to the high X-ray activity of the system (Barthelmy et al.

A puzzling, slightly submerged, single tidal notch has been reported from the carbonate coasts of the northeastern Adriatic Sea. This paper attempts to explain the origin and the recent evolution of this marine erosion feature and the reasons for its uniqueness in the late Holocene. After reviewing how tidal notches are usually formed, a comparison of recent measurements of bioerosion rates carried out in the area show that when the contribution of dissolution processes can be neglected, bioerosion rates of the deepening of tidal-notch profiles appear to be very low (often <0.1 mm/y) along the coasts of Istria, in contrast to higher rates (between 0.2 and 1.0 mm/y) generally reported in other Mediterranean areas. Such a low rate of bioerosion implies a long period favourable to tidal-notch development. Several glacial isostatic adjustment computations show that relative sea level changes in the area during the last few millennia may correspond to a period of equilibrium between the regional tectonic subsidence and hydro-isostatic emergence during which relative sea level changes were limited, permitting development of the tidal notch observed. The submergence of the notch is consistent with a coseismic subsidence in late Roman time. After this, a new tidal notch could not form at the present sea level because of the limited amount of local bioerosion and the relatively large rate of sea level rise.

NCS1 proteins are H(+) /Na(+) symporters specific for the uptake of purines, pyrimidines and related metabolites. In this article we study the origin, diversification and substrate specificity of fungal NCS1 transporters. We show that the two fungal NCS1 subfamilies, Fur and Fcy, and plant homologues, originate through independent horizontal transfers from prokaryotes, and that expansion by gene duplication led to the functional diversification of fungal NCS1. We characterized all Fur proteins of the model fungus Aspergillus nidulans and discovered novel functions and specificities. Homology modelling, substrate docking, molecular dynamics and systematic mutational analysis in three Fur transporters with distinct specificities identified residues critical for function and specificity, located within a major substrate binding site, in transmembrane segments TMS1, TMS3, TMS6 and TMS8. Most importantly, we predict and confirm that residues determining substrate specificity are located not only in the major substrate binding site, but also in a putative outward-facing selective gate. Our evolutionary and structure-function analysis contributes in the understanding of the molecular mechanisms underlying the functional diversification of eukaryotic NCS1 transporters, and in particular, forward the concept that selective channel-like gates might contribute to substrate specificity.

Bone metabolism has not been systematically studied in primary (AL) amyloidosis. Thus we prospectively evaluated bone remodeling indices in 102 patients with newly diagnosed AL amyloidosis, 35 healthy controls, 35 newly diagnosed myeloma and 40 monoclonal gammopathy of undetermined significance patients. Bone resorption markers (C-telopeptide of type-1 collagen, N-telopeptide of type-1 collagen) and osteoclast regulators (soluble receptor activator of nuclear factor-κB ligand (sRANKL), osteoprotegerin (OPG)) were increased in AL patients compared with controls (P<0.01), but bone formation was unaffected. Myeloma patients had increased bone resorption and decreased bone formation compared with AL patients, while sRANKL/OPG ratio was markedly decreased in AL, due to elevated OPG in AL (P<0.001). OPG correlated with N-terminal pro-brain natriuretic peptide (P<0.001) and was higher in patients with cardiac involvement (P=0.028) and advanced Mayo stage (P=0.001). OPG levels above the upper value of healthy controls was associated with shorter survival (34 versus 91 months; P=0.026), while AL patients with OPG levels in the top quartile had very short survival (12 versus 58 months; P=0.024). In Mayo stage 1 disease, OPG identified patients with poor survival (12 versus >60 months; P=0.012). We conclude that increased OPG in AL is not only a compensation to osteoclast activation but may also reflect early cardiac damage and may identify patients at increased risk of death within those with earlier Mayo stage.

Bone metabolism has not been systematically studied in primary (AL) amyloidosis. Thus we prospectively evaluated bone remodeling indices in 102 patients with newly diagnosed AL amyloidosis, 35 healthy controls, 35 newly diagnosed myeloma and 40 monoclonal gammopathy of undetermined significance patients. Bone resorption markers (C-telopeptide of type-1 collagen, N-telopeptide of type-1 collagen) and osteoclast regulators (soluble receptor activator of nuclear factor-κB ligand (sRANKL), osteoprotegerin (OPG)) were increased in AL patients compared with controls (P<0.01), but bone formation was unaffected. Myeloma patients had increased bone resorption and decreased bone formation compared with AL patients, while sRANKL/OPG ratio was markedly decreased in AL, due to elevated OPG in AL (P<0.001). OPG correlated with N-terminal pro-brain natriuretic peptide (P<0.001) and was higher in patients with cardiac involvement (P = 0.028) and advanced Mayo stage (P = 0.001). OPG levels above the upper value of healthy controls was associated with shorter survival (34 versus 91 months; P = 0.026), while AL patients with OPG levels in the top quartile had very short survival (12 versus 58 months; P = 0.024). In Mayo stage 1 disease, OPG identified patients with poor survival (12 versus 460 months; P = 0.012). We conclude that increased OPG in AL is not only a compensation to osteoclast activation but may also reflect early cardiac damage and may identify patients at increased risk of death within those with earlier Mayo stage.

INTRODUCTION: Heart failure (HF) treatment attracts a share of intensive research because of its poor HF prognosis. In the past decades, the prognosis of HF has improved considerably, mainly as a consequence of the progress that has been made in the pharmacological management of HF. AREAS COVERED: This article reviews the outpatient pharmacological management of chronic HF due to left ventricular systolic dysfunction and offers recommendations on the use of various drugs. In addition, the present article attempts to provide practical therapeutic algorithms based on current clinical strategies. EXPERT OPINION: Continued research directed toward identifying factors associated with high pharmacotherapy guideline adherence and understanding of variants that influence response to drugs will hopefully halt or reverse the major pathophysiological mechanisms involved in this syndrome.

Summary: In the phase III MM-003 trial, pomalidomide plus low-dose dexamethasone (POM+LoDEX) improved overall survival (OS) versus high-dose dexamethasone (HiDEX) in 455 patients with relapsed and refractory multiple myeloma (RRMM) after treatment with bortezomib and lenalidomide. Here, a two-stage Weibull method was used to adjust for the crossover of patients in the HiDEX arm to pomalidomide-based therapy. The adjusted difference in median OS between patients in the POM+LoDEX and HiDEX arms was 7·0 months (12·7 vs. 5·7 months, respectively). These findings provide important evidence for understanding the clinical efficacy of pomalidomide on OS benefits seen in RRMM patients. © 2014 John Wiley & Sons Ltd.

PURPOSE: The identification of childhood acute lymphoblastic leukemia (ch-ALL) patients who are at a higher risk of chemotherapy resistance and relapse is essential for successful treatment decisions, despite the application of novel therapies. The aim of the study is the evaluation of BCL2 and BAX expression for the prognosis of ch-ALL patients treated with Berlin-Frankfurt-Munster (BFM) backbone protocol. METHODS: Bone marrow specimens were obtained at the time of diagnosis and on day 33 following BFM treatment induction from 82 ch-ALL patients, as well as from 63 healthy children. Following extraction, total RNA was reverse transcribed and BCL2 and BAX expression levels were determined by qPCR. RESULTS: BCL2 expression and BCL2/BAX ratio were strongly upregulated in ch-ALL compared to healthy children and were correlated with favorable prognostic disease features. Increased levels of BCL2 and BAX expression were associated with disease remission, as ch-ALL patients with lower expression ran a significantly higher risk of M2-M3 response, positive MRD and poor survival outcome. Moreover, the upregulation of BCL2 and BAX following BFM treatment induction was shown to represent an independent predictor of patients' short-term relapse, which was further confirmed in ch-ALL patients with favorable prognostic markers. CONCLUSIONS: In conclusion, BCL2 and BAX could be effectively used for an enhanced prediction of BFM-treated patients' outcome.

Oxidative stress refers to cellular or molecular damage caused by reactive oxygen species, which especially occurs in age-related conditions as a result of an imbalance between the production of reactive oxygen species and the antioxidant defense response. Dry age-related macular degeneration (AMD) and exfoliation syndrome (XFS) are two common and complex age-related conditions that can cause irreversible vision loss. Two subtypes of AMD, which is the leading cause of blindness in the Western world, exist: the most prevalent dry type and the most severe wet type. Early dry AMD is characterized by formation of drusen, which are sub-retinal deposits, in the macular area and may progress to geographic atrophy with more dramatic manifestation. XFS is a systemic disorder of the extracellular matrix characterized by the accumulation of elastic fibrils that leads, in most cases, to glaucoma development with progressive and irreversible vision loss. Due to the aging population, the prevalence of these already-widespread conditions is increasing and is resulting in significant economic and psychological costs for individuals and for society. The exact composition of the abnormal drusen and XFS material as well as the mechanisms responsible for their production and accumulation still remain elusive, and consequently treatment for both diseases is lacking. However, recent epidemiologic, genetic and molecular studies support a major role for oxidative stress in both dry AMD and XFS development. Understanding the early molecular events in their pathogenesis and the exact role of oxidative stress may provide novel opportunities for therapeutic intervention for the prevention of progression to advanced disease

Important earthquakes are often accompanied by vertical-land displacements. Therefore in coastal areas they may result in rapid changes of the relative sea level. An essential tool for the study of coastal paleoseismicity is the identification of fossil paleoshorelines, paying special attention to sea-level indicators that are consistent or provide evidence of rapid relative sea-level change.Here, different types of sea-level indicators that are often used in literature in order to determine changes in fossil shorelines are summarized. Information is also provided regarding four case studies of important earthquakes that occurred in Greece (in AD 365, 1953, and 1956) and in Japan (in 1923).

Paleoceanographic proxies, such as marine micropaleontology, sedimentology and organic geochemistry havebeen performed in the sediment record of SK-3 gravity core (total length 217cm, water depth 249m) in order toprovide possible determination of late interglacial-Holocene the paleoenvironmental changes, at the southwestern margin of Cyclades plateau in the SW Aegean Sea. The sediment core exhibits two sapropels layer; thefirst one is associated with sapropel S1. The second sapropelic layer which we focus on represents anoxicconditions during the high sea-level warm event associated with sapropel S5 deposition.

Detailed pollen analyses were performed at the lower sapropelic deposits of the marine core SK-3 within theframework of a multiproxy palaeoceanographic-palaeoenvironmental study. Pollen flora is characterized byhigh arboreal pollen abundances, mainly deciduous Quercus, together with Pinus, Juniperus and otherdeciduous taxa. A transition is marked from vegetation where Mediterranean elements appear more abundanttowards mixed deciduous woodland. In the upper part of the deposits an expansion of Abies, Pinus and Fagushas been recorded. The overall vegetation pattern adds significant evidence about the terrestrialpalaeoenvironmental conditions during deposition of sapropel S5.

Insulinomas are rare pancreatic neuroendocrine tumors that are most commonly benign, solitary, and intrapancreatic. Uncontrolled insulin overproduction from the tumor produces neurological and adrenergic symptoms of hypoglycemia. Biochemical diagnosis is confirmed by the presence of Whipple's triad, along with corroborating measurements of blood glucose, insulin, proinsulin, C-peptide, β-hydroxybutyrate, and negative tests for hypoglycemic agents during a supervised fasting period. This is accompanied by accurate preoperative localization using both invasive and non-invasive imaging modalities. Following this, careful preoperative planning is required, with the ensuing procedure being preferably carried out laparoscopically. An integral part of the laparoscopic approach is the application of laparoscopic intraoperative ultrasound, which is indispensable for accurate intraoperative localization of the lesion in the pancreatic region. The extent of laparoscopic resection is dependent on preoperative and intraoperative findings, but most commonly involves tumor enucleation or distal pancreatectomy. When performed in an experienced surgical unit, laparoscopic resection is associated with minimal mortality and excellent long-term cure rates. Furthermore, this approach confers equivalent safety and efficacy rates to open resection, while improving cosmesis and reducing hospital stay. As such, laparoscopic resection should be considered in all cases of benign insulinoma where adequate surgical expertise is available.

Outcomes for patients with multiple myeloma (MM) have improved significantly over the past decade. Despite these advances, MM remains incurable and an unmet medical need remains for patients who are relapsed and/or refractory. Panobinostat is a potent, oral pan-deacetylase inhibitor that elicits anti-myeloma activity through epigenetic modulation of gene expression and disruption of protein metabolism. Preclinical data demonstrated that panobinostat has synergistic effects on myeloma cells when combined with bortezomib and dexamethasone. In a Phase III clinical trial evaluating bortezomib and dexamethasone in combination with panobinostat or placebo in patients with relapsed or relapsed and refractory MM (PANORAMA 1), panobinostat led to a significant increase in median progression-free survival. Panobinostat is currently under regulatory review with a recent accelerated approval granted for the treatment of relapsed disease, in which both bortezomib and immunomodulatory drugs have failed. Here, we summarize the preclinical, pharmacokinetic and clinical data for panobinostat in MM. © 2015 Informa UK, Ltd.

BACKGROUND: Besides the vast success and reliability of lower extremity joint replacement, deep and periprosthetic infection remains a serious complication of such operations. Many publications addressing periprosthetic infection have remarked about this "devastating" complication, with a risk around 1% after total hip arthroplasty and between 1% and 2% after total knee arthroplasty. The purpose of this study is to assess current trends in prevention of contamination with improved up-to-date pre-operative skin preparation methods and intra-operative draping. METHODS: A literature review was conducted in MEDLINE, Web of Science, and the Cochrane database, looking for high-quality papers summarizing the most widely held and up-to-date concepts of perioperative measures for reducing infection, focusing on the best available evidence concerning skin preparation for joint arthroplasty (THR and THR) and surgical draping. RESULTS: Current evidence suggests the use of alcohol solutions for pre-operative painting with emphasis on the use of chlorhexidine gluconate solutions beginning the night before surgery. Hair removal should be performed in the operating room with electric clippers, not razor blades. In order to enhance drape adhesion to the skin, the use of iodophor-in-alcohol solutions is recommended over the traditional scrub-and-paint technique. Disposable non-woven drapes are superior to reusable woven cotton/linen drapes in resisting bacterial penetration. Finally, the use of adherent plastic adhesive incision drapes for the prophylaxis of post-operative surgical site infections is considered not necessary in orthopedic surgery. CONCLUSIONS: The importance of skin preparation and adequate and reliable draping cannot be overemphasized for infection prevention, especially in clean operations such as THR and TKR. Thorough and strict protocols are mandatory for every department, as well as education curricula for operating room personnel. Further randomized studies are mandatory to specify the effect of the above measures, their pitfalls, and their improvement, along with further crucial details such as cost-benefit analysis of different pre-operative preparations in preventing infections.

A publicity campaign run in Athens by the Alexander S. Onassis Public Benefit Foundation in October 2013 in order to advertise its acquisition of the Cavafy Archive, until then lying in relevant obscurity, turned into a media disaster when critics and members of the public protested against what they argued was a misquoting of the highly revered Alexandrian. In this paper, I am looking at this rather entertaining story of misunderstood intentions in order to suggest that even though Cavafy himself may be shown to have enjoyed history as fragmented experience, and despite the fact that the modern archive is one of often conflicting partialities rather than one of completeness, we, as consumers of Cavafy’s oeuvre, tend to sustain his long-established position as a paragon of Greek culture, canonised through his own nonconformity. As a typical case of ‘archive fever’, the events described here confirm the political specificity of any literary discourse, even when conducted out of context (or especially so).

We compared the safety and efficacy of siltuximab (S), an anti-interleukin-6 chimeric monoclonal antibody, plus bortezomib (B) with placebo (plc) + B in patients with relapsed/refractory multiple myeloma in a randomized phase 2 study. Siltuximab was given by 6 mg/kg IV every 2 weeks. On progression, B was discontinued and high-dose dexamethasone could be added to S/plc. Response and progression-free survival (PFS) were analyzed pre-dexamethasone by European Group for Blood and Marrow Transplantation (EBMT) criteria. For the 281 randomized patients, median PFS for S + B and plc + B was 8.0 and 7.6 months (HR 0.869, P = 0.345), overall response rate was 55 versus 47% (P = 0.213), complete response rate was 11 versus 7%, and median overall survival (OS) was 30.8 versus 36.8 months (HR 1.353, P = 0.103). Sustained suppression of C-reactive protein, a marker reflective of inhibition of interleukin-6 activity, was seen with S + B. Siltuximab did not affect B pharmacokinetics. Siltuximab/placebo discontinuation (75 versus 66%), grade ≥3 neutropenia (49 versus 29%), thrombocytopenia (48 versus 34%), and all-grade infections (62 versus 49%) occurred more frequently with S + B. The addition of siltuximab to bortezomib did not appear to improve PFS or OS despite a numerical increase in response rate in patients with relapsed or refractory multiple myeloma. © 2014 Wiley Periodicals, Inc.

The recent IceCube discovery of 0.1-1 PeV neutrinos of astrophysical origin opens up a new era for high-energy astrophysics. Although there are various astrophysical candidate sources, a firm association of the detected neutrinos with one (or more) of them is still lacking. A recent analysis of plausible astrophysical counterparts within the error circles of IceCube events showed that likely counterparts for nine of the IceCube neutrinos include mostly BL Lacs, among which Mrk 421. Motivated by this result and a previous independent analysis on the neutrino emission from Mrk 421, we test the BL Lac-neutrino connection in the context of a specific theoretical model for BL Lac emission. We model the spectral energy distribution (SED) of the BL Lacs selected as counterparts of the IceCube neutrinos using a one-zone leptohadronic model and mostly nearly simultaneous data. The neutrino flux for each BL Lac is self-consistently calculated, using photon and proton distributions specifically derived for every individual source. We find that the SEDs of the sample, although different in shape and flux, are all well fitted by the model using reasonable parameter values. Moreover, the model-predicted neutrino flux and energy for these sources are of the same order of magnitude as those of the IceCube neutrinos. In two cases, namely Mrk 421 and 1H 1914-194, we find a suggestively good agreement between the model prediction and the detected neutrino flux. Our predictions for all the BL Lacs of the sample are in the range to be confirmed or disputed by IceCube in the next few years of data sampling.

The recent IceCube discovery of 0.1-1 PeV neutrinos of astrophysical origin opens up a new era for high-energy astrophysics. Although there are various astrophysical candidate sources, a firm association of the detected neutrinos with one (or more) of them is still lacking. A recent analysis of plausible astrophysical counterparts within the error circles of IceCube events showed that likely counterparts for nine of the IceCube neutrinos include mostly BL Lacs, among which Mrk 421. Motivated by this result and a previous independent analysis on the neutrino emission from Mrk 421, we test the BL Lac-neutrino connection in the context of a specific theoretical model for BL Lac emission. We model the spectral energy distribution (SED) of the BL Lacs selected as counterparts of the IceCube neutrinos using a one-zone leptohadronic model and mostly nearly simultaneous data. The neutrino flux for each BL Lac is self-consistently calculated, using photon and proton distributions specifically derived for every individual source. We find that the SEDs of the sample, although different in shape and flux, are all well fitted by the model using reasonable parameter values. Moreover, the model-predicted neutrino flux and energy for these sources are of the same order of magnitude as those of the IceCube neutrinos. In two cases, namely Mrk 421 and 1H 1914-194, we find a suggestively good agreement between the model prediction and the detected neutrino flux. Our predictions for all the BL Lacs of the sample are in the range to be confirmed or disputed by IceCube in the next few years of data sampling.

The Neolithic settlement of Dispilió (lake Orestiás, northern Greece) is a unique site due to its continual inhabitation from the Middle Neolithic (5400 BC) to the Chalcolithic (3600 BC) and its exceptional location at the shore of Lake Orestiás (also known as Lake Kastoria). The plant landscape shaping of the area has been examined by correlating pollen and non-pollen palynomorphs (NPPs) from both on-site and off-site records. The examined pollen profiles bear concrete evidence of agricultural activities and land use in the area. The local pollen assemblages identified, each of them corresponding either to a different kind or intensity of exploitation of natural resources, display the diachronic evolution of the cultural landscape during more than 2000 years of human activity. The successive phases of intense human impact on vegetation patterns are in good accordance with the periods of major constructing activities described by the archaeological study of the Dispilió settlement. Finally, the differences on palynomorph accumulation pathways of the examined records made possible the distinction between local and “regional” plant landscapes and related human activities.

The polycystins PC1 and PC2 are emerging as major players in mechanotransduction, a process that influences all steps of the invasion/metastasis cascade. We hypothesized that PC1 and PC2 facilitate cancer aggressiveness. Immunoblotting, RT-PCR, semi-quantitative and quantitative real-time PCR and FACS analyses were employed to investigate the effect of polycystin overexpression in colorectal cancer (CRC) cells. The impact of PC1 inhibition on cancer-cell proliferation was evaluated through an MTT assay. In vitro data were analyzed by Student's t-test. HT29 human xenografts were treated with anti-PC1 (extracellular domain) inhibitory antibody and analyzed via immunohistochemistry to determine the in vivo role of PC1 in CRC. Clinical significance was assessed by examining PC1 and PC2 protein expression in CRC patients (immunohistochemistry). In vivo and clinical data were analyzed by non-parametric tests, Kaplan-Meier curves, log-rank test and Cox model. All statistical tests were two-sided. PC1 overexpression promotes epithelial-to-mesenchymal transition (EMT) in HCT116 cells, while PC2 overexpression results in upregulation of the mTOR pathway in SW480 cells. PC1 inhibition causes reduced cell proliferation in CRC cells inducing tumor necrosis and suppressing EMT in HT29 tumor xenografts. In clinical study, PC1 and PC2 overexpression associates with adverse pathological parameters, including invasiveness and mucinous carcinomas. Moreover, PC1 overexpression appears as an independent prognostic factor of reduced recurrence-free survival (HR = 1.016, p = 0.03) and lowers overall survival probability, while aberrant PC2 expression predicts poor overall survival (p = 0.0468). These results support, for the first time, a direct link between mechanosensing polycystins (PC1 and PC2) and CRC progression.

Pomalidomide is a distinct immunomodulatory agent with significant activity in relapsed/refractory multiple myeloma (RRMM). The optimal treatment schedule in patients with RRMM who have received multiple lines of treatment, including bortezomib and lenalidomide, is 4 mg/day on days 1-21 of a 28-day cycle in combination with weekly low-dose dexamethasone. Improved responses and outcomes relative to traditional therapies continue to be confirmed in recently completed and ongoing trials. Pomalidomide exhibits direct tumoricidal, immunomodulatory, anti-angiogenic and anti-inflammatory activities, which facilitate combination therapy with agents with complementary mechanisms of action, resulting in greater anti-myeloma effects than single-agent therapy or previous combination therapies. For example, in combination with proteasome inhibitors and traditional chemotherapeutic agents in doublet or triplet regimens, pomalidomide provides high rates of durable response, and represents an important new treatment option for patients with RRMM requiring effective new therapies. Additionally, pomalidomide maintains its efficacy and tolerability profile in difficult-to-treat patients, including the elderly, patients with poor cytogenetics and those with renal impairment. This review summarises the clinical development of pomalidomide and discusses this effective agent for the treatment of patients with RRMM in the context of current myeloma treatment options, as well as potential future directions to further improve patient outcomes.

Background Health-related quality of life (HRQoL) is an important element for consideration in treatment decisions in patients with relapsed/refractory multiple myeloma (RRMM). The pivotal MM-003 (A Phase 3, Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Pomalidomide in Combination With Low-Dose Dexamethasone vs. High-Dose Dexamethasone in Patients With Refractory Multiple Myeloma or Relapsed and Refractory Multiple Myeloma and Companion Study [NIMBUS]) randomized, open-label, multicenter, phase III trial demonstrated improved progression-free survival (PFS) and prolonged overall survival (OS) with pomalidomide (POM) plus low-dose dexamethasone (POM + LoDEX) versus high-dose dexamethasone (HiDEX) in patients with RRMM in whom lenalidomide (LEN) and bortezomib (BORT) had failed. MM-003 also investigated HRQoL as a predefined secondary end point. Patients and Methods Recruited patients (n = 455) were refractory to their last treatment and had failed LEN and BORT after ≥ 2 consecutive cycles of each (alone or in combination). Eight clinically relevant and validated HRQoL domains from the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-MY20, and EQ-5D questionnaires were selected for analysis. Time to symptom worsening based on minimally important differences (MIDs) was calculated. Results Clinically meaningful improvements in HRQoL as determined by MIDs, regression analyses, and best response analyses were observed more frequently in patients receiving POM + LoDEX than in those receiving HiDEX. POM + LoDEX significantly extended median time to clinically meaningful worsening in HRQoL versus HiDEX in 4 HRQoL domains and demonstrated a trend in an additional 3 domains. Patients in the HiDEX arm experienced earlier HRQoL deterioration compared with those in the POM + LoDEX arm in each domain analyzed. Conclusion POM + LoDEX offer good clinical outcomes that lead to improved and prolonged HRQoL compared with HiDEX in patients with RRMM and end-stage disease. © 2015 Elsevier Inc.

The combination of fluticasone propionate (FLP) and salmeterol (SAL) is often used in clinical practice for the treatment of pulmonary disorders. The purpose of this study was to explore the pharmacokinetics (PK) of inhaled FLP and SAL, after concomitant administration, in healthy male and female subjects using two dry powder inhalers. Plasma concentration (C)-time (t) data were obtained from a single dose, two-sequence, two-period, crossover (2 x 2) bioequivalence (BE) study. Activated charcoal was co-administered in order to prohibit absorption from the gastrointestinal tract. A number of 60 subjects were recruited, while 57 of them completed the study and were included in the PK analysis. Initially, PK parameters of FLP and SAL were estimated using the classic non-compartmental methods. Subsequently, BE assessment was applied to the estimated PK parameters of the two dry powder inhalers. Special focus was placed on the population PK analysis of the C-t data, which were pooled together. `Treatment' (i.e., test or reference) and `period' of the BE study were considered as covariates. A variety of structural and residual error models were tested to find the one which best described the plasma C-t data of FLP and SAL. Demographic data were also evaluated for their impact on the PK parameters. Several goodness-of-fit criteria were utilized. The non-compartmental PK estimates of this study were in agreement with previously reported values. The population PK analysis showed that FLP data were described by a two compartment model with first-order absorption and elimination kinetics. Body weight was found to affect significantly absorption rate constant, inter-compartmental clearance, and volume of distribution of the peripheral compartment. As body weight increases, the values of these PK parameters also rise. For SAL, the best results were obtained when a two-compartment disposition model was used assuming very rapid absorption kinetics (like intravenous bolus) and first-order elimination kinetics. Gender was found to be a significant covariate on clearance, with men exhibiting higher clearance than women. (C) 2015 Elsevier B.V. All rights reserved.

Ketamine is an anesthetic with antidepressant properties. The rapid and lasting effect of ketamine observed in preclinical and clinical research makes it a promising therapeutic to improve current major depression (MD) treatment. Our work intended to evaluate whether the combined use of classic antidepressants (imipramine or fluoxetine) and ketamine would improve the antidepressant response. Using an animal model of depressive-like behavior, we show that the addition of ketamine to antidepressants anticipates the behavioral response and accelerates the neuroplastic events when compared with the use of antidepressants alone. In conclusion, our results suggest the need for a reappraisal of the current pharmacological treatment of MD.

Ketamine is an anesthetic with antidepressant properties. The rapid and lasting effect of ketamine observed in preclinical and clinical research makes it a promising therapeutic to improve current major depression (MD) treatment. Our work intended to evaluate whether the combined use of classic antidepressants (imipramine or fluoxetine) and ketamine would improve the antidepressant response. Using an animal model of depressive-like behavior, we show that the addition of ketamine to antidepressants anticipates the behavioral response and accelerates the neuroplastic events when compared with the use of antidepressants alone. In conclusion, our results suggest the need for a reappraisal of the current pharmacological treatment of MD.

Intercostal hernias are rare, and usually occur following injuries of the thoracic wall. The scope of this report is to present a case of a 53-year-old obese patient that developed a transdiaphragmatic intercostal hernia. The patient presented with a palpable, sizeable, reducible mass in the right lateral thoracic wall, with evident bowel sounds in the area, 6 months after a motor-vehicle accident. On computed tomography (CT), the hernia sac contained part of the liver and part of the ascending colon. A surgical repair of the defect was performed, using a prosthetic patch. The patient's postoperative course was uneventful and she remains recurrence free at 12 months after surgery. Intercostal hernias should be suspected following high-impact injuries of the thoracic wall, and CT scans will facilitate the diagnosis of intercostal hernia. We consider the surgical repair of the defect, with placement of a prosthetic mesh, as the treatment of choice to ensure a favorable outcome.

A study on living coccolithophores from the euphotic zone is conducted in the northeastern Aegean Sea, anarea under the direct influence of the Black Sea waters inflowing into the Aegean. A total of 53 planktonsamples from 5 stations have been collected during four sampling periods between 2011 and 2014. Highconcentrations of Emiliania huxleyi and low concentrations of oligotrophic species, such asholococcolithophores, are indicative of a direct influence of the Black Sea waters inflow on the coccolithophoreassemblages in the northeastern Aegean Sea.

Morbidity and mortality attributable to chronic hepatitis C virus (HCV) infection are increasing in many countries as the infected population ages. Models were developed for 15 countries to quantify and characterize the viremic population, as well as estimate the number of new infections and HCV related deaths from 2013 to 2030. Expert consensus was used to determine current treatment levels and outcomes in each country. In most countries, viremic prevalence has already peaked. In every country studied, prevalence begins to decline before 2030, when current treatment levels were held constant. In contrast, cases of advanced liver disease and liver related deaths will continue to increase through 2030 in most countries. The current treatment paradigm is inadequate if large reductions in HCV related morbidity and mortality are to be achieved.

OBJECTIVES: The objective of this study was to define the natural genotypic variation of the HIV-1 integrase gene across Europe for epidemiological surveillance of integrase strand-transfer inhibitor (InSTI) resistance. METHODS: This was a multicentre, cross-sectional study within the European SPREAD HIV resistance surveillance programme. A representative set of 300 samples was selected from 1950 naive HIV-positive subjects newly diagnosed in 2006-07. The prevalence of InSTI resistance was evaluated using quality-controlled baseline population sequencing of integrase. Signature raltegravir, elvitegravir and dolutegravir resistance mutations were defined according to the IAS-USA 2014 list. In addition, all integrase substitutions relative to HXB2 were identified, including those with a Stanford HIVdb score ≥ 10 to at least one InSTI. To rule out circulation of minority InSTI-resistant HIV, 65 samples were selected for 454 integrase sequencing. RESULTS: For the population sequencing analysis, 278 samples were retrieved and successfully analysed. No signature resistance mutations to any of the InSTIs were detected. Eleven (4%) subjects had mutations at resistance-associated positions with an HIVdb score ≥ 10. Of the 56 samples successfully analysed with 454 sequencing, no InSTI signature mutations were detected, whereas integrase substitutions with an HIVdb score ≥ 10 were found in 8 (14.3%) individuals. CONCLUSIONS: No signature InSTI-resistant variants were circulating in Europe before the introduction of InSTIs. However, polymorphisms contributing to InSTI resistance were not rare. As InSTI use becomes more widespread, continuous surveillance of primary InSTI resistance is warranted. These data will be key to modelling the kinetics of InSTI resistance transmission in Europe in the coming years.

Prions induce lethal neurodegeneration and consist of PrPSc, an aggregated conformer of the cellular prion protein PrPC. Antibody-derived ligands to the globular domain of PrPC (collectively termed GDL) are also neurotoxic. Here we show that GDL and prion infections activate the same pathways. Firstly, both GDL and prion infection of cerebellar organotypic cultured slices (COCS) induced the production of reactive oxygen species (ROS). Accordingly, ROS scavenging, which counteracts GDL toxicity in vitro and in vivo, prolonged the lifespan of prion-infected mice and protected prion-infected COCS from neurodegeneration. Instead, neither glutamate receptor antagonists nor inhibitors of endoplasmic reticulum calcium channels abolished neurotoxicity in either model. Secondly, antibodies against the flexible tail (FT) of PrPC reduced neurotoxicity in both GDL-exposed and prion-infected COCS, suggesting that the FT executes toxicity in both paradigms. Thirdly, the PERK pathway of the unfolded protein response was activated in both models. Finally, 80% of transcriptionally downregulated genes overlapped between prion-infected and GDL-treated COCS. We conclude that GDL mimic the interaction of PrPSc with PrPC, thereby triggering the downstream events characteristic of prion infection.

The performance analysis of the classical M / G / 1 queue, under a general mixed joining/balking strategy was carried out recently by Kerner (Stoch Mod 24:364–375, 2008), who used an analytic approach based on the supplementary variable method. The tractability of the corresponding queueing system with state-dependent arrival rates is particularly significant, as it has important applications in situations where the customers are strategic. In this paper, we present an alternative path for the analysis of the same system, using purely probabilistic arguments.

The novel platinum (II) dimethyl complexes Pt(κ2-L1)Me2 and Pt(κ2-L1)Me2 (1), Pt(κ2-L2a)Me2 (2a) and Pt(κ2-L2b)Me2 (2b) bearing the functionalised N-heterocyclic carbenes (NHCs), L1 = 1-(2-diphenylphosphinoethyl)-3-(2,6-diisopropyl-phenyl)-imidazol-2-ylidene, L2a = 1-(2-pyridyl)-3-(2,6-diisopropyl-phenyl)-imidazol-2-ylidene, L2b = 1-(2-(3-picolinyl))-3-(2, 6-diisopropyl-phenyl)-imidazol-2-ylidene, react with the acid [H(Et2O)2+B(ArF)4-], ArF = 3, 5-(CF3)2C6H3, in the presence of various neutral donors (Dn) to give the salts [{Pt(κ2-L)(Me)(Dn)}+{B(ArF)4}-], where Dn occupies specifically the site trans to the P and the CNHC donor atoms of the coordinated ligands L1 and L2a, L2b, respectively. Spectroscopic data give evidence that the same selectivity prevails when other acids are employed. Activation of the Cl-CH2Cl bond by 2b led to [Pt(κ2-L2b)(Me)Cl], while reaction of CH3I with the dimethyl complexes led to isolable [Pt(κ2-L)Me3I] species.

This paper examines the effects of quantitative easing (QE) announcements by the European Central Bank, the Bank of Japan and the Bank of England on exchange rate dynamics. Using intraday data of three major exchange rates (EUR/USD, GBP/USD, JPY/USD), we apply a univariate APARCH(1,1) model and include QE dummies to empirically investigate how exchange rates are affected in mean and volatility. The empirical results indicate: (i) a direct negative impact on GBP and JPY and no effect of their volatility around the QE announcements of the corresponding central banks, (ii) a delayed devaluation of EUR and an increase of its volatility before and after the ECB’s announcements. Furthermore, the behavior of dynamic conditional correlation among currencies is investigated across the QE announcements. We find a decline in the conditional correlation between EUR and GBP around the announcements by the BoE. These findings highlight the differences on the credibility and effectiveness of the monetary easing strategies and provide important implications from the investors’ and policy makers’ perspective.

We introduce a new method to localize lightwaves. We show how the interaction of a gain medium with a planar deep-UV plasmonic heterostructure, at its zero-vg point, strongly localizes light. A quantum-coherent drive provides a means to control the localization and dramatically improve the dynamics. © OSA 2015.

We introduce a new method to localize lightwaves. We show how the interaction of a gain medium with a planar deep-UV plasmonic heterostructure, at its zero-vg point, strongly localizes light. A quantum-coherent drive provides a means to control the localization and dramatically improve the dynamics. © 2015 OSA.

We analyzed near-infrared data of the nearby galaxy IC5063 taken with the Very Large Telescope SINFONI instrument. IC5063 is an elliptical galaxy that has a radio jet nearly aligned with the major axis of a gas disk in its center. The data reveal multiple signatures of molecular and atomic gas that has been kinematically distorted by the passage of the jet plasma or cocoon within an area of ∼1 kpc2. Concrete evidence that the interaction of the jet with the gas causes the gas to accelerate comes from the detection of outflows in four different regions along the jet trail: near the two radio lobes, between the radio emission tip and the optical narrow-line-region cone, and at a region with diffuse 17.8 GHz emission midway between the nucleus and the north radio lobe. The outflow in the latter region is biconical, centered 240 pc away from the nucleus, and oriented perpendicularly to the jet trail. The diffuse emission that is observed as a result of the gas entrainment or scattering unfolds around the trail and away from the nucleus with increasing velocity. It overall extends for ≳700 pc parallel and perpendicular to the trail. Near the outflow starting points, the gas has a velocity excess of 600-1200 km s-1 with respect to ordered motions, as seen in [Fe ii], {Pa}α , or {{{H}}}2 lines. High {{{H}}}2 (1-0) S(3)/S(1) flux ratios indicate non-thermal excitation of gas in the diffuse outflow.

We analyzed near-infrared data of the nearby galaxy IC5063 taken with the Very Large Telescope SINFONI instrument. IC5063 is an elliptical galaxy that has a radio jet nearly aligned with the major axis of a gas disk in its center. The data reveal multiple signatures of molecular and atomic gas that has been kinematically distorted by the passage of the jet plasma or cocoon within an area of ∼1 kpc2. Concrete evidence that the interaction of the jet with the gas causes the gas to accelerate comes from the detection of outflows in four different regions along the jet trail: near the two radio lobes, between the radio emission tip and the optical narrow-line-region cone, and at a region with diffuse 17.8 GHz emission midway between the nucleus and the north radio lobe. The outflow in the latter region is biconical, centered 240 pc away from the nucleus, and oriented perpendicularly to the jet trail. The diffuse emission that is observed as a result of the gas entrainment or scattering unfolds around the trail and away from the nucleus with increasing velocity. It overall extends for ≳700 pc parallel and perpendicular to the trail. Near the outflow starting points, the gas has a velocity excess of 600-1200 km s-1 with respect to ordered motions, as seen in [Fe ii], {Pa}α , or {{{H}}}2 lines. High {{{H}}}2 (1-0) S(3)/S(1) flux ratios indicate non-thermal excitation of gas in the diffuse outflow.

BACKGROUND: Liver resection is currently the most efficient curative approach for a wide variety of liver tumors. The application of modern techniques and new surgical devices has improved operative outcomes. Radiofrequency ablation is used more often for liver parenchymal transection. This study aimed to assess the efficacy and safety of radiofrequency ablation-assisted liver resection. METHODS: A retrospective study of 145 consecutive patients who underwent radiofrequency ablation-assisted liver resection was performed. Intraoperative blood loss, need for transfusion or intraoperative Pringle maneuver, the duration of liver parenchymal transection, perioperative complications, and postoperative morbidity and mortality were all evaluated. RESULTS: Fifty minor and ninety-five major liver resections were performed. The mean intraoperative blood loss was 251 mL, with a transfusion rate of 11.7%. The Pringle maneuver was necessary in 12 patients (8.3%). The mean duration for parenchymal transection was 51.75 minutes. There were 47 patients (32.4%) with postoperative complications. There is no mortality within 30 days after surgery. CONCLUSIONS: Radiofrequency ablation-assisted liver resection permits both major and minor liver resections with minimal blood loss and without occlusion of hepatic inflow. Furthermore it decreases the need for blood transfusion and reduces morbidity and mortality. (

Since 2011, Romania has faced an HIV outbreak among injecting drug users (IDUs). Our aim was to identify and describe clinical and epidemiological patterns of this outbreak. A cross-sectional study enrolled 138 IDUs diagnosed with HIV infection between 2011 and 2013 with 58 sexually infected individuals included as the control group. The IDUs had a long history of heroin abuse (10 years) and a recent history of new psychostimulant injection (3-4 years). Classical epidemiological data and molecular techniques were used to describe the transmission dynamics. A high prevalence of hepatitis C virus (HCV) coinfection was noted (98.6%) compared to the control group (10.3%) (p<0.001). IDUs had initially been infected with HCV. HIV infection was more recent, linked to starting injecting stimulants. HIV subtype analysis showed a predominance of the local F1 strain in both IDUs and sexually infected patients; in IDUs it also identified 28 CRF14_BG recombinants and six unique recombinant forms (URFs) between F1 and CRF14_BG. A few patients from both risk groups were infected with subtype B. Among IDUs, CRF14_BG was associated with a lower CD4 cell count and more advanced stages of disease, which correlated with CXCR4 tropism. Phylogenetic analysis revealed the spread of HIV through three major IDU clusters of recent date. Among IDUs with CRF14_BG, some reported travel abroad (Spain, Greece). By identifying clusters of IDUs with related viruses, molecular epidemiologic methods provide valuable information on patterns of HIV transmission that can be useful in planning appropriate harm reduction interventions.

We report the detection of three new X-ray transients and one recurrent X-ray source in recent XMM-Newton observations of the M31 disk. Two 100-ks observations were carried out on 2015-06-28 (ObsID 0763120101; June) and 2015-08-11 (ObsID 0763120301; August).

The aim of this study is to analyze and quantify the future projections of heat waves in Greece. For this reason, specific climatic indices were used in the analysis concerning absolute, percentile and duration indices defined by the CCl/CLIVAR/JCOMM Expert Team (ET) on Climate Change Detection and Indices (ETCCDI). The future projections (SRES A1B) of these indices such as summer days, tropical days, maximum daily maximum air temperature, warm days, tropical nights, maximum daily minimum air temperature, warm nights and warm spell duration were carried out using six regional climate models from the ENSEMBLES project, concerning the near future 2031-2050 and the far future 2071-2100 compared to the reference period 1961-1990. The ensemble means along with the inter-model-standard deviations of the examined extreme indices for the future model projections are presented and analyzed. Further, the findings of this analysis are discussed against recent recorded heat waves during 2007, in order to understand if such events are even more extreme or common in the future climate. It is very likely, that the anomalies observed in 2007, especially for extreme indices of minimum air temperature, could be more frequent considered as typical events by the end of the 21th century. © 2014 Elsevier B.V.

The cytokine granulocyte colony-stimulating factor (G-CSF) binds to its receptor (G-CSFR) to stimulate hematopoietic stem cell mobilization, myelopoiesis, and the production and activation of neutrophils. In response to exercise-induced muscle damage, G-CSF is increased in circulation and G-CSFR has recently been identified in skeletal muscle cells. While G-CSF/G-CSFR activation mediates pro- and anti-inflammatory responses, our understanding of the role and regulation in the muscle is limited. The aim of this study was to investigate, in vitro and in vivo, the role and regulation of G-CSF and G-CSFR in skeletal muscle under conditions of muscle inflammation and damage. First, C2C12 myotubes were treated with lipopolysaccharide (LPS) with and without G-CSF to determine if G-CSF modulates the inflammatory response. Second, the regulation of G-CSF and its receptor was measured following eccentric exercise-induced muscle damage and the expression levels we investigated for redox sensitivity by administering the antioxidant N-acetylcysteine (NAC). LPS stimulation of C2C12 myotubes resulted in increases in G-CSF, interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNFα) messenger RNA (mRNA) and an increase in G-CSF, IL-6, and MCP-1 release from C2C12 myotubes. The addition of G-CSF following LPS stimulation of C2C12 myotubes increased IL-6 mRNA and cytokine release into the media, however it did not affect MCP-1 or TNFα. Following eccentric exercise-induced muscle damage in humans, G-CSF levels were either marginally increased in circulation or remain unaltered in skeletal muscle. Similarly, G-CSFR levels remained unchanged in response to damaging exercise and G-CSF/G-CSFR did not change in response to NAC. Collectively, these findings suggest that G-CSF may cooperate with IL-6 and potentially promote muscle regeneration in vitro, whereas in vivo aseptic inflammation induced by exercise did not change G-CSF and G-CSFR responses. These observations suggest that different models of inflammation produce a different G-CSF response.

Self-determination theory posits that satisfaction of the needs for autonomy, competence and relatedness represents the basic nutriments for humans’ optimal functioning. It also postulates that with greater the degree to which these three needs are equally satisfied, the quality of motivation is further enhanced. Yet, this premise has remained relatively underexplored. In this correlational study, we surveyed Greek middle-school students (N = 435; 47.1% males; Mage = 13.95; SD = 0.85) and investigated to what extent balanced need satisfaction contributes over and above the need satisfaction in the prediction of quality of motivation in physical education contexts. Path analysis showed that need satisfaction along with balanced need satisfaction were linked with autonomous motivation but not with controlled motivation. The present findings imply that balanced satisfaction of the needs for autonomy, competence and relatedness can be an additional source of optimal motivation and functioning in physical education.

Observations of gamma-ray-bursts and jets from active galactic nuclei reveal that the jet flow is characterized by a high radiative efficiency and that the dissipative mechanism must be a powerful accelerator of non-thermal particles. Shocks and magnetic reconnection have long been considered as possible candidates for powering the jet emission. Recent progress via fully-kinetic particle-in-cell simulations allows us to revisit this issue on firm physical grounds. We show that shock models are unlikely to account for the jet emission. In fact, when shocks are efficient at dissipating energy, they typically do not accelerate particles far beyond the thermal energy, and vice versa. In contrast, we show that magnetic reconnection can deposit more than 50 per cent of the dissipated energy into non-thermal leptons as long as the energy density of the magnetic field in the bulk flow is larger than the rest-mass energy density. The emitting region, i.e. the reconnection downstream, is characterized by a rough energy equipartition between magnetic fields and radiating particles, which naturally accounts for a commonly observed property of blazar jets.

In this article the author argues that the teaching of religion(s) in education, in a social pedagogical context, can encourage community cohesion especially when, during the current harsh crisis, the need for cohesion seems to be of paramount importance in enabling seemingly insurmountable problems to be overcome. At the same time minorities become vulnerable and diversity, a matter of high priority, comes to the fore. The author reviews evidence of research on the effect of educational intervention within Religious Education on student attitudes toward religious diversity. He proposes that constructivist methodology, using theatre/drama as a means of Religious Education, could give people the choice to be critical religious believers and active members in a society applyingthe fundamental social pedagogical principle of tolerance to and respect for the ‘other’.

Religious Education (RE) in Greece is a compulsory school subject according the 2011 new framework for compulsory education, entitled ‘New School’. This article focuses on two statutory documents for RE, ‘The Curriculum for RE’ and the ‘The Teacher’s Guide for RE’, and the pilot scheme of the new curriculum running in school years, 2011–2014, in 188 schools (primary and secondary education). Findings of the research demonstrate that, though the revision seems inevitable, the pedagogical and theological dimension of the RE curriculum is radical as it is based on contemporary theories and methodologies of the construction of the curriculum and RE approaches. However, the article indicates constructivist and critical approaches to RE that influenced the change to an actual non-confessional compulsory subject and also highlighted the tension between an overall constructivist approach to learning and the traditional orthodox content of much of the curriculum. The author opens a discussion on problematic aspects that need to be taken in to consideration when revising the curriculum.

This study is an attempt to address the issue of religion in the public sphere and secularism. Since the Eastern Orthodox Church has been established by the Greek constitution (1975) as the prevailing religion of Greece, there are elements of legal agreements-which inevitably spawn interactions-between state and Church in different areas. One such area is Religious Education. This article focuses on Religious Education (RE) in Greece which is a compulsory school subject and on two important interventions that highlight the interplay between religion, politics and education: firstly the new Curriculum for RE (2011) and secondly the introduction of an Islamic RE (2014) in a Greek region (Thrace) where Christians and Muslims have lived together for more than four centuries. The researches are based on fieldwork research and they attempt to open the discussion on the role of RE in a secular education system and its potential for coexistence and social cohesion.

Purpose: The clinical outcome of multiple myeloma (MM) is heterogeneous. A simple and reliable tool is needed to stratify patients with MM. We combined the International Staging System (ISS) with chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization after CD138 plasma cell purification and serum lactate dehydrogenase (LDH) to evaluate their prognostic value in newly diagnosed MM (NDMM). Patients and Methods: Clinical and laboratory data from 4,445 patients with NDMM enrolled onto 11 international trials were pooled together. The K-adaptive partitioning algorithm was used to define the most appropriate subgroups with homogeneous survival. Results: ISS, CA, and LDH data were simultaneously available in 3,060 of 4,445 patients. We defined the following three groups: revised ISS (R-ISS) I (n = 871), including ISS stage I (serum β2-microglobulin level < 3.5 mg/L and serum albumin level ≥ 3.5 g/dL), no high-risk CA [del(17p) and/or t(4;14) and/or t(14;16)], and normal LDH level (less than the upper limit of normal range); R-ISS III (n = 295), including ISS stage III (serum β2-microglobulin level > 5.5 mg/L) and high-risk CA or high LDH level; and R-ISS II (n = 1,894), including all the other possible combinations. At a median follow-up of 46 months, the 5-year OS rate was 82% in the R-ISS I, 62% in the R-ISS II, and 40% in the R-ISS III groups; the 5-year PFS rates were 55%, 36%, and 24%, respectively. Conclusion: The R-ISS is a simple and powerful prognostic staging system, and we recommend its use in future clinical studies to stratify patients with NDMM effectively with respect to the relative risk to their survival. © 2015 American Society of Clinical Oncology. All rights reserved.

The epidemiology of multiple myeloma (MM) is an increasingly investigated field, with many controversies. This systematic review aims to synthesize meta-analyses examining risk factors for MM so as to provide a comprehensive, parsimonious summary of the current evidence. Eligible meta-analyses were sought in PubMed adopting a predefined algorithm, without any restriction of publication language; end-of-search date was October 10, 2014. The selection of eligible studies and data extraction were performed by working in pairs, independently and blindly to each other; in case of disagreement, consensus with the whole team was reached. Among the 22 ultimately included meta-analyses, 9 examined occupational factors, 4 assessed aspects of lifestyle (smoking, alcohol, body mass index), 5 evaluated the presence of other diseases, and 4 addressed genetic factors as potential risk factors of MM. A vast compendium of significant associations arose, including farming, occupation as a firefighter, occupation as a hairdresser, exposures to chemicals or pesticides, overweight and obesity, patterns of alcohol intake, pernicious anemia, ankylosing spondylitis, gene promoter methylation, and polymorphisms. In conclusion, MM is a multifactorial disease, encompassing a wide variety of risk factors that span numerous life aspects. Further accumulation of evidence through meta-analyses is anticipated in this rapidly growing field. © 2015 Elsevier Inc.

Purpose: The aim of International Myeloma Working Group was to develop practical recommendations for the use of magnetic resonance imaging (MRI) in multiple myeloma (MM). Methods: An interdisciplinary panel of clinical experts on MM and myeloma bone disease developed recommendations for the value of MRI based on data published through March 2014. Recommendations: MRI has high sensitivity for the early detection of marrow infiltration by myeloma cells compared with other radiographic methods. Thus, MRI detects bone involvement in patients with myeloma much earlier than the myeloma-related bone destruction, with no radiation exposure. It is the gold standard for the imaging of axial skeleton, for the evaluation of painful lesions, and for distinguishing benign versus malignant osteoporotic vertebral fractures. MRI has the ability to detect spinal cord or nerve compression and presence of soft tissue masses, and it is recommended for the workup of solitary bone plasmacytoma. Regarding smoldering or asymptomatic myeloma, all patients should undergo whole-body MRI (WB-MRI; or spine and pelvic MRI if WB-MRI is not available), and if they have > one focal lesion of a diameter > 5 mm, they should be considered to have symptomatic disease that requires therapy. In cases of equivocal small lesions, a second MRI should be performed after 3 to 6 months, and if there is progression on MRI, the patient should be treated as having symptomatic myeloma. MRI at diagnosis of symptomatic patients and after treatment (mainly after autologous stem-cell transplantation) provides prognostic information; however, to date, this does not change treatment selection. © 2015 by American Society of Clinical Oncology.