A benchmark is a reference point for comparisons established from the value of a performance indicator. In order to create benchmarks for volleyball, we used performance data from each team of the Greek Volley League from the season 2005-2006 until the season 2016-2017 (N = 143). We considered the effectiveness of 14 parameters from five skills: serve, attack after passing, attack after defence, block and pass. The results showed that high-level teams of the Greek championship, which finished in positions 1-4, had as benchmarks: (a) in serve, two aces every five serve errors, while teams 9-12 had two aces every six errors, (b) in attack after passing one error or one passive block every four kills, while teams 9-12 had one every five kills, (c) in attack after defence one error or one passive block every three kills versus every two kills for 9-12 and (d) one error every nine passes on the target against every seven passes for 9-12. Overall, the results of this study indicate that success in volleyball can be explained with skill performance indicators, expressed as the ratio of successful to unsuccessful attempts, or with a ratio of successful attempts per set, in case of block skill. ABSTRACT FROM AUTHOR
Objective. Autonomy-supportive and psychologically controlling parenting have been shown to relate to positive and negative developmental outcomes, respectively. Most research that addresses antecedents of these parenting constructs has focused on the predictive role of between-parent differences (e.g., personality). To gain insight in dynamics of within-parent changes in reported parenting, this study focused on daily fluctuations in reported autonomy-supportive and psychologically controlling parenting and examined the role of parents’ need satisfaction and need frustration in accounting for those fluctuations. Design. Mothers (M age = 45) and fathers (M age = 47) of 198 adolescents (M age = 15) participated in a 7-day diary study. Results. Multilevel modeling provided evidence for significant day-to-day variability in both parenting dimensions. Daily fluctuations in need satisfaction were related to daily fluctuations in reported autonomy-supportive parenting and daily fluctuations in need frustration were related to daily fluctuations in reported psychologically controlling parenting. These associations were not moderated by between-parent differences in those parenting dimensions. Conclusions. The findings provide evidence for the role of parents’ own needs-related experiences in their daily display of autonomy-supportive and psychologically controlling parenting.
Context. We carried out new observations of two fields in the star-forming northern ring of M 31 with XMM-Newton with each one of them consisting of two exposures of about 100 ks each. A previous XMM-Newton survey of the entire M 31 galaxy revealed extended diffuse X-ray emission in these regions. Aims: We study the population of X-ray sources in the northern disc of M 31 by compiling a complete list of X-ray sources down to a sensitivity limit of ∼7 × 1034 erg s-1 (0.5-2.0 keV) and improve the identification of the X-ray sources. The major objective of the observing programme was the study of the hot phase of the interstellar medium (ISM) in M 31. The analysis of the diffuse emission and the study of the ISM is presented in a separate paper. Methods: We analysed the spectral properties of all detected sources using hardness ratios and spectra if the statistics were high enough. We also checked for variability. In order to classify the sources detected in the new deep XMM-Newton observations, we cross-correlated the source list with the source catalogue of a new survey of the northern disc of M 31 carried out with the Chandra X-ray Observatory and the Hubble Space Telescope (Panchromatic Hubble Andromeda Treasury, PHAT) as well as with other existing catalogues. Results: We detected a total of 389 sources in the two fields of the northern disc of M 31 observed with XMM-Newton. We identified 43 foreground stars and candidates and 50 background sources. Based on a comparison with the results of the Chandra/PHAT survey, we classify 24 hard X-ray sources as new candidates for X-ray binaries. In total, we identified 34 X-ray binaries and candidates and 18 supernova remnants (SNRs) and candidates. We studied the spectral properties of the four brightest SNRs and confirmed five new X-ray SNRs. Three of the four SNRs, for which a spectral analysis was performed, show emission mainly below 2 keV, which is consistent with shocked ISM. The spectra of two of them also require an additional component with a higher temperature. The SNR [SPH11] 1535 has a harder spectrum and might suggest that there is a pulsar-wind nebula inside the SNR. For all SNRs in the observed fields, we measured the X-ray flux or calculated upper limits. We also carried out short-term and long-term variability studies of the X-ray sources and found five new sources showing clear variability. In addition, we studied the spectral properties of the transient source SWIFT J004420.1+413702, which shows significant variation in flux over a period of seven months (June 2015 to January 2016) and associated change in absorption. Based on the likely optical counterpart detected in the Chandra/PHAT survey, the source is classified as a low-mass X-ray binary. Based on observations obtained with XMM-Newton, an ESA science mission with instruments and contributions directly funded by ESA Member States and NASA.Tables A.1-A.6 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/620/A28
Tsoukos, A, Veligekas, P, Brown, LE, Terzis, G, and Bogdanis, GC. Delayed effects of a low-volume, power-type resistance exercise session on explosive performance. J Strength Cond Res 32(3): 643-650, 2018-This study examined the delayed effects of a power-type training session on explosive performance. Seventeen well-trained male power and team sport athletes (age: 22.7 ± 5.5 years, height: 181 ± 8 cm, body mass: 80.7 ± 8.6 kg, body fat: 9.2 ± 1.7%, 1 repetition maximum (1RM) half-squat: 163 ± 29 kg) performed 4 sessions (2 experimental and 2 control) 1 week apart in a randomized and counterbalanced order. Explosive performance was assessed before, 24 and 48 hours after a low-volume, power-type training session (5 × 4 jump squats at 40% 1RM with 3 minutes rest), as well as before and after 24 and 48 hours of rest (control). Dependent variables were as follows: countermovement jump (CMJ), reactive strength index (RSI) during a drop jump, leg press maximum isometric force, and rate of force development (RFD) at 3 time windows: 0-100, 0-200, and 0-300 milliseconds. Analysis of variance revealed no changes in the control conditions. In contrast after training, CMJ was improved by 5.1 ± 1.0% and 3.0 ± 1.0% at 24 and 48 hours, respectively, compared with baseline. The RSI improved by 10.7 ± 2.1% only at 24 hours. The RFD increased at all time windows at 24 hours (range of improvement: 9.7 ± 3.4% to 18.3 ± 4.1%, p < 0.01). However, at 48 hours, improvement was only seen in RFD0-100 (9.8 ± 3.1%, p < 0.01). These findings suggest that a low-volume, power-type training session results in delayed enhancement of explosive muscle performance, which is greatest at 24 hours after the activity. Athletes are advised to perform power-type training 1 day before competition or a high-quality training session to improve their performances.
Cloud computing is a reality in most business sectors. Hospitals have been more reluctant to adopt cloud technology due to strict data security regulations. Cloud could provide economies of scale reducing Information Technology spending in the Greek state-owned hospitals, while giving the opportunity to the hospitals to upgrade their profile offering web-based services. We propose a simple, robust and easy to apply approach for the Greek hospitals, focusing on clinical and laboratory data in order to move to the cloud environment. To the best of our knowledge, there is no other study regarding the adoption of cloud infrastructure in the Greek hospital sector. This innovative method could transform the business model of the hospitals.
We report the results of AstroSat and NuSTAR observations of the Be/X-ray binary pulsar SXP 15.3 in the Small Magellanic Cloud during its outburst in late 2017, when the source reached a luminosity level of ∼1038 erg s-1, close to the Eddington limit. The unprecedented broad-band coverage of the source allowed us to perform timing and spectral analysis between 3 and 80 keV. The pulse profile exhibits a significant energy dependence, and morphs from a double-peaked profile to a single broad pulse at energies >15 keV. This can be explained by a spectral hardening during an intensity dip seen between the two peaks of the pulse profile. We detect a Cyclotron Resonance Scattering Feature at ∼5 keV in the X-ray spectrum, independent of the choice of the continuum model. This indicates a magnetic field strength of 6 × 1011 G for the neutron star.
We report an optical/UV jet and counterjet in M84, previously unreported in archival Hubble Space Telescope imaging. With archival VLA, ALMA, and Chandra imaging, we examine the first well-sampled spectral energy distribution of the inner jet of M84, where we find that multiple co-spatial spectral components are required. In particular, the ALMA data reveal that the radio spectrum of all four knots in the jet turns over at approximately 100 GHz, which requires a second component for the bright optical/UV emission. Further, the optical/UV has a soft spectrum and is inconsistent with the relatively flat X-ray spectrum, which indicates a third component at higher energies. Using archival VLA imaging, we have measured the proper motion of the innermost knots at 0.9 ± 0.6 and 1.1 ± 0.4c, which when combined with the low jet-to-counterjet flux ratio yields an orientation angle for the system of {74}-18+9°. In the radio, we find high fractional polarization of the inner jet of up to 30% while in the optical no polarization is detected (<8%). We investigate different scenarios for explaining the particular multicomponent spectral energy distribution (SED) of the knots. Inverse Compton models are ruled out due to the extreme departure from equipartition and the unrealistically high total jet power required. The multicomponent SED can be naturally explained within a leptohadronic scenario, but at the cost of very high power in relativistic protons. A two-component synchrotron model remains a viable explanation, but more theoretical work is needed to explain the origin and properties of the electron populations.
Introduction: Use of Integrated Health Information Systems (IHIS) for the provision of healthcare services benefits both healthcare professionals and patients, while requiring continuous evaluation and upgrading to fully support its role.
Aim: The main purpose of the study was to develop an evaluation framework for hospitals utilizing IHIS, within the three main areas identified as Human factor, Technology and Organization.
Material and methods: The questionnaire consisted of 43 questions, with 17 questions (related to categories procedures, system quality and satisfaction), 25 questions (related to categories, safety and collaboration) and 1 question related to accessibility to the system (within the category system quality). Three open questions were added to evaluate users' perception on what was needed for the improvement of health services in their respective hospitals for all 3 variables being evaluated. The open questions were included to allow participants to express their opinion in a more detailed setting. A database was developed, and the data were processed and analyzed.
Results: Factor analysis formed 5 categories for the evaluation framework. Cronbach's alpha coefficient was found in all categories to be above > 0.85.
Conclusion: Evaluation frameworks can be designed, developed and implemented by using different methodologies. For an evaluation framework to be effective it should be designed and implemented based on the aims and purpose of the research and the specific needs of the particular healthcare setting or hospital. Considering the categories satisfaction, collaboration, safety, system quality, procedures, and by using Likert scale and open questions in the current study, DIPSA can provide a holistic image of IHIS by evaluating any hospital system.
PURPOSE: The purpose of this study was the development of new quantitative methodologies for the general (total) COL11A1 gene and the C transcript (RT-qPCR methods for A and E transcripts have already been developed by our group previously), the quantification of all COL11A1 transcripts and the investigation for the first time of their potential association with histopathological prognostic factors in lung cancer. METHODS: Real-time RT-qPCR methodologies with dual hybridization probes were developed on the Light Cycler 1.5 platform (Roche,Germany). All COL11A1 transcripts were measured in 27 cDNA lung tissue specimens in a blinded fashion (8 control and 19 non-small cell lung cancer (NSCLC) tissues with known histopathological data). Statistical analysis was performed with the IBM SPSS program. RESULTS: The novel real-time RT-qPCR methodologies were appropriately validated. All 19 NSCLC samples were positive for the general COL11A1 transcript (range 11.2-1198.0 copies/mug total RNA, while 5 out of 8 control samples were negative: mean values were also statistically significantly different (p<0.001). In 4 tumor samples (21%), no specific COL11A1 transcript was detected. Transcript C was detected in only 3 tumor samples. Regarding transcripts A and E, 13 out of 19 tumor samples were positive for either one (68%) and 11 for both (58%). CONCLUSIONS: No other statistically significant association of the specific transcripts with histopathological data was observed, most probably due to the limited number of samples. As the number of general COL11A1 transcripts/microg exceeds the sum of A+E+C transcripts in all samples, there is opportunity for discovery and identification of other transcripts as well
In this study, we aimed to investigate the different routes through which perceived goal structures, and in turn mastery-approach and performance-approach goals in mathematics, predict subsequent academic performance. Path analyses with a sample of Turkish adolescents (N = 369; 49.1% males; M-age = 16.67 years, SD = 1.85) revealed two distinct paths. After controlling for mid-year grades, we found perceived mastery goal structures to relate (positively) to mastery-approach goals, which in turn positively predicted end-year grades through challenge seeking. In contrast, perceived performance goal structures related positively to both performance approach and performance-avoidance goals with the former directly predicting higher end-year grades, and the latter being related negatively to challenge seeking. These findings imply that there may exist different paths that can predict academic performance.
The well-characterized association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05-restricted CD8T-cell responses toward the conserved Gag KK10 (residues 263 to 272) and polymerase (Pol) KY9 (residues 901 to 909) epitopes. We studied the impact of the 3 amino acid differences between HLA-B*27:05 and the closely related HLA-B*27:02 on the HIV-specific CD8T-cell response hierarchy and on immune control of HIV. Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 are associated with slower disease progression and lower viral loads. The effect of HLA-B*27:02 appeared to be consistently stronger than that of HLA-B*27:05. In contrast to HLA-B*27:05, the immunodominant HIV-specific HLA-B*27:02-restricted CD8T-cell response is to a Nef epitope (residues 142 to 150 [VW9]), with Pol KY9 subdominant and Gag KK10 further subdominant. This selection was driven by structural differences in the F pocket, mediated by a polymorphism between these two HLA alleles at position 81. Analysis of autologous virus sequences showed that in HLA-B*27:02-positive subjects, all three of these CD8T-cell responses impose selection pressure on the virus, whereas in HLA-B*27:05-positive subjects, there is no Nef VW9-mediated selection pressure. These studies demonstrate that HLA-B*27:02 mediates protection against HIV disease progression that is at least as strong as or stronger than that mediated by HLA-B*27:05. In combination with the protective Gag KK10 and Pol KY9 CD8T-cell responses that dominate HIV-specific CD8T-cell activity in HLA-B*27:05-positive subjects, a Nef VW9-specific response is additionally present and immunodominant in HLA-B*27:02-positive subjects, mediated through a polymorphism at residue 81 in the F pocket, that contributes to selection pressure against HIV.CD8T cells play a central role in successful control of HIV infection and have the potential also to mediate the eradication of viral reservoirs of infection. The principal means by which protective HLA class I molecules, such as HLA-B*27:05 and HLA-B*57:01, slow HIV disease progression is believed to be via the particular HIV-specific CD8T cell responses restricted by those alleles. We focus here on HLA-B*27:05, one of the best-characterized protective HLA molecules, and the closely related HLA-B*27:02, which differs by only 3 amino acids and which has not been well studied in relation to control of HIV infection. We show that HLA-B*27:02 is also protective against HIV disease progression, but the CD8T-cell immunodominance hierarchy of HLA-B*27:02 differs strikingly from that of HLA-B*27:05. These findings indicate that the immunodominant HLA-B*27:02-restricted Nef response adds to protection mediated by the Gag and Pol specificities that dominate anti-HIV CD8T-cell activity in HLA-B*27:05-positive subjects.
We compare two of the most successful models for the description and analysis of drug release data. The fractal kinetics approach leading to release profiles described by a Weibull function and the fractional kinetics approach leading to release profiles described by a Mittag-Leffler function. We used Monte Carlo simulations to generate artificial release data from euclidean and fractal substrates. We have also used real release data from the literature and found that both models are capable in describing release data up to roughly 85% of the release. For larger times both models systematically overestimate the number of particles remaining in the release device.
The supernova impostor SN 2010da located in the nearby galaxy NGC 300, later identified as a likely supergiant B[e] high-mass X-ray binary, was simultaneously observed by NuSTAR and XMM-Newton between 2016 December 16 and 20, over a total time span of ∼310 ks. We report the discovery of a strong periodic modulation in the X-ray flux with a pulse period of 31.6 s and a very rapid spin-up, and confirm therefore that the compact object is a neutron star. We find that the spin period is changing from 31.71 s to 31.54 s over that period, with a spin-up rate of -5.56 × 10-7 s s-1, likely the largest ever observed from an accreting neutron star. The spectrum is described by a power-law and a disc blackbody model, leading to a 0.3-30 keV unabsorbed luminosity of 4.7 × 1039 erg s-1. Applying our best-fitting model successfully to the spectra of an XMM-Newton observation from 2010, suggests that the lower fluxes of NGC 300 ULX1 reported from observations around that time are caused by a large amount of absorption, while the intrinsic luminosity was similar as seen in 2016. A more constant luminosity level is also consistent with the long-term pulse period evolution approaching an equilibrium value asymptotically. We conclude that the source is another candidate for the new class of ultraluminous X-ray pulsars.
. Int J Financ Econ Trade [Internet]. 2018;2(2):11-17.
The aim of this study is to examine the correlation of the service quality dimensions to the overall customer satisfaction in the Greek banking sector, following its restructuring due to the mergers and the takeovers during the current financial crisis period (2009 - 2015), and to analyze in particular the case of Piraeus Bank, the biggest Greek commercial Bank. The research conducted so as the data to be collected, was drawn from a customer sample of the Piraeus Bank and as for the measurements used, are based on the widely accepted SERVQUAL model, as it is proposed by Parasuraman et al. (1988), where the five dimensions of service quality merged: reliability, responsiveness, empathy, assurance and tangibles. According to the results, all service quality dimensions are positively related to the customer satisfaction. The greatest impact, regarding customer satisfaction, was observed most in the dimensions of empathy and reliability. Moreover, it was discovered that a certain type of customer discontent is on the verge of being manifested among the considered bank services.
Spontaneous Generations: A Journal for the History and Philosophy of Science [Internet]. 2018;9(1):35-37.
I raise two challenges for scientific realists. The first is a pessimistic meta-induction (PMI), but not of the more common type, which focuses on rejected theories and abandoned entities. Rather, the PMI I have in mind departs from conceptual change, which is ubiquitous in science. Scientific concepts change over time, often to a degree that is difficult to square with the stability of their referents, a sine qua non for realists. The second challenge is to make sense of successful scientific practice that was centered on entities that have turned out to be fictitious.
. Επιστημονική Επιθεώρηση του ΠΜΣ "Ορθόδοξη Χριστιανική Θεολογία και Θρησκευτικός Πλουραλισμός" περιοδικό "Διάλογος: Σπουδές στη Θεολογία". 2018;9:483-492.eap-th-fanaras_georgiadou.pdf
. Documents pour l'histoire du français langue étrangère ou seconde [Internet]. 2018;60-61.
Les modifications considérables entreprises dans le domaine de l’enseignement en Grèce dans les premières décennies du XXe siècle, se répercutent aussi dans le domaine de l’enseignement du français qui s’adapte ainsi au gré d’une législation qui définit la politique éducative et éditoriale. Dans ce cadre sont publiés des manuels inspirés de la méthode directe qui se servent de l’image comme support de l’enseignement. Notre étude se focalise sur l’analyse du rôle de l’image dans les représentations de la culture française véhiculées dans la Collection enfantine de Théodore Kyprios, publiée en Grèce dans les années 1930. Cette série de manuels constitue un tournant dans la conception du matériel didactique utilisé à l’époque pour l’enseignement du français langue étrangère : l’image n’est plus utilisée comme un support au texte mais elle est plutôt conçue comme un outil autonome et indispensable pour l’enseignement-apprentissage de la langue étudiée. L’image n’est plus soumise au texte, comme dans la plupart des manuels de l’époque, mais c’est plutôt le texte qui est soumis à l’image. Sous l’influence de la méthode directe, l’image devient le pivot central d’un enseignement qui bannit le recours à la langue maternelle et qui favorise les fonctions d’observation et d’intuition de l’élève. La culture s’introduit progressivement dans la collection des manuels de Kyprios, suivant le schéma suggéré par les programmes officiels, et se fait plus visible dans les manuels complémentaires
Objectives: To assess the effectiveness, clinical performance, and potential adverse effects of early anterior crossbite correction through opening of the bite.
Subjects and methods: The sample consisted of 16 consecutive patients (8.0 ± 0.9, range: 6.2-9.3 years) with dental anterior crossbite in the mixed dentition who were treated through posterior bite opening. Patients were prospectively followed until a minimum of 6 months post-treatment and there were no drop-outs.
Results: In 14 patients (87.5 per cent), the anterior crossbite was corrected. Results remained stable without any retention regime. Active treatment of the successfully treated cases lasted 2.5 months (range: 0.6-8.9). Crossbite correction of central incisors was achieved by a 2.05 mm (range: 0.97-5.45) forward movement and 9.25° (range: 2.32-14.52°) buccal inclination of the crowns (P < 0.05). The antagonists showed spontaneous adaptation of their position in the opposite direction (P < 0.05). No important adverse effects were recorded.
Limitations: This was a non-comparative controlled study, on a limited sample.
Conclusions: Bite opening is a promising, simple, and non-compliance approach for early dental anterior crossbite correction. The technique of 3D superimposition and analysis of digital models used here, allowed precise evaluation of single tooth movement in all three planes of space.
The emergence of the information technologies has seriously changed the healthcare system. Thus, health professionals need to be well-educated in order to respond successfully to the challenges of their job. In higher education programs in, biomedical informatics and health informatics are continuously developing. At this study more than 500 universities and colleges in Europe were checked in order to find related educational programs at all academic levels. The outcome of the research includes 316 study programs at undergraduate and postgraduate level including a variety of specializations. The majority of these programs are taking place in Czech Republic, Ireland and Austria. In contrast, countries such as Croatia and Cyprus have very low number of study programs in these fields.
OBJECTIVE: We estimated and compared the risk of clinically identified acquired drug resistance under immediate initiation [the currently recommended antiretroviral therapy (ART) initiation strategy], initiation with CD4 cell count less than 500 cells/μl and initiation with CD4 cell count less than 350 cells/μl.
DESIGN: Cohort study based on routinely collected data from the HIV-CAUSAL collaboration.
METHODS: For each individual, baseline was the earliest time when all eligibility criteria (ART-naive, AIDS free, and others) were met after 1999. Acquired drug resistance was defined using the Stanford classification as resistance to any antiretroviral drug that was clinically identified at least 6 months after ART initiation. We used the parametric g-formula to adjust for time-varying (CD4 cell count, HIV RNA, AIDS, ART regimen, and drug resistance testing) and baseline (calendar period, mode of acquisition, sex, age, geographical origin, ethnicity and cohort) characteristics.
RESULTS: In 50 981 eligible individuals, 10% had CD4 cell count more than 500 cells/μl at baseline, and 63% initiated ART during follow-up. Of 2672 tests for acquired drug resistance, 794 found resistance. The estimated 7-year risk (95% confidence interval) of acquired drug resistance was 3.2% (2.8,3.5) for immediate initiation, 3.1% (2.7,3.3) for initiation with CD4 cell count less than 500 cells/μl, and 2.8% (2.5,3.0) for initiation with CD4 cell count less than 350 cells/μl. In analyses restricted to individuals with baseline in 2005-2015, the corresponding estimates were 1.9% (1.8, 2.5), 1.9% (1.7, 2.4), and 1.8% (1.7, 2.2).
CONCLUSION: Our findings suggest that the risk of acquired drug resistance is very low, especially in recent calendar periods, and that immediate ART initiation only slightly increases the risk. It is unlikely that drug resistance will jeopardize the proven benefits of immediate ART initiation.
The purpose of the present study was to investigate the effect of a short-term, high-intensity, low-volume Mixed Martial Arts (MMA) specific strength and conditioning training program on performance in national level MMA athletes. Seventeen experienced fighters were divided into two groups: (A) Specific Training Group (STG; n = 10), which followed a specific strength and conditioning program designed according to the demands of MMA competition and (B) Regular Training Group (RTG; n = 7), in which participants followed a regular strength and conditioning program commonly used by MMA athletes. Before and after the four-week training period (3 days per week), body composition, aerobic fitness, strength, power and speed were evaluated. Significant improvements in estimated VO, average power during the 2000 m rowing, bench press, back squat and deadlift 1RM, SJ power, CMJ height power, medicine ball throw velocity, 10 m sprint and 2 m take down speed and fat-free mass were found only in the STG (3.7 to 22.2%; p < 0.05; Hedge's g = -0.42 - 4.1). No significant changes were found for the RTG (p = 0.225 to 0.811). Significant differences between the groups were found for almost all post-training assessments (p < 0.05; Hedge's g = 0.25 - 1.45) as well as for the percentage changes from pre to post training (p < 0.05; Hedge's g: 0.25 - 1.45). Significant relationships were found between percentage changes in fat-free mass, endurance capacity, muscle strength/power and speed (r: -0.475 to 0.758; p < 0.05). These results suggest that a high-intensity low-volume strength and conditioning training intervention designed according to the demands of MMA competition may result in significant performance improvements for well-trained fighters.
The purpose of this meta-analysis was to examine the effectiveness of Mosston and Ashworth’s (2008) practice and reciprocal styles of teaching on motor skill acquisition of school and university students. A systematic search in bibliographical databases led to the identification of 23 relevant studies published in peer-reviewed journals. Using certain methodological and statistical criteria, we retained six studies for further analysis. We estimated proper Effect Size (ES) statistics for each study and each teaching style. Heterogeneity of the ESs was almost negligence for the reciprocal style and moderate to large for the practice style (I2 > 50%). Both teaching styles appear to produce rather large effects, with the practice style (mean d = 1.16) having larger effects than the reciprocal style (mean d = 0.94). This meta-analysis provides an overview and synthesis of relevant studies and highlights both teaching styles for increasing K-12 and university students’ motor skill learning. The results are discussed in light of the Spectrum theory.
Keywords: meta-analysis, Spectrum, practice style, reciprocal style, motor skill
This study compared knee angle-specific neuromuscular adaptations after two low-volume isometric leg press complex training programmes performed at different muscle lengths. Fifteen young males were divided into two groups and trained three times per week for 6 weeks. One group (n = 8) performed 5-7 sets of 3 s maximum isometric leg press exercise, with 4 min recovery, with knee angle at 85° ± 2° (longer muscle-tendon unit length; L-MTU). The other group (n = 7) performed the same isometric training at a knee angle of 145° ± 2° (180°= full extension; shorter muscle-tendon unit length; S-MTU). During the recovery after each set of isometric exercise, participants performed two CMJ every minute, as a form of complex training. Maximum isometric force (MIF) and rate of force development (RFD) were measured over a wide range of knee angles. Countermovement jump (CMJ) performance and maximum half-squat strength (1RM) were also assessed. Training at S-MTU induced a large increase of MIF (22-58%, p < 0.02) and RFD (18-43%, p < 0.05 to 0.001) at knee angles close to the training angle and resulted in a 14° ± 9° shift of the force vs. knee joint angle relationship towards extended knee joint angles (p = 0.001). In contrast, training at L-MTU, resulted in a moderate and similar (≈12.3%, p = 0.028) improvement of force at all knee angles. CMJ performance and 1RM were equally increased in both groups after training by 10.4% ± 8.3% and 7.8% ± 4.7% (p < 0.001), respectively. Low-volume maximal isometric leg-press complex training at S-MTU causes angle-specific adaptations in isometric strength and RFD, while dynamic muscle performance is independent of muscle length during training.
BACKGROUND & AIMS: The effects of long-term antiviral therapy on survival have not been adequately assessed in chronic hepatitis B (CHB). In this 10-centre, ongoing cohort study, we evaluated the probability of survival and factors affecting survival in Caucasian CHB patients who received long-term entecavir/tenofovir therapy. METHODS: We included 1,951 adult Caucasians with CHB, with or without compensated cirrhosis and without hepatocellular carcinoma (HCC) at baseline, who received entecavir/tenofovir for >/=12months (median, six years). Kaplan-Meier estimates of cumulative survival over time were obtained. Standardized mortality ratios (SMRs) were calculated by comparing death rates with those in the Human Mortality Database. RESULTS: The one-, five-, and eight-year cumulative probabilities were 99.7, 95.9, and 94.1% for overall survival, 99.9, 98.3, and 97.4% for liver-related survival, and 99.9, 97.8, and 95.8% for transplantation-free liver-related survival, respectively. Overall mortality was independently associated with older age and HCC development, liver-related mortality was associated with HCC development only, and transplantation-free liver-related mortality was independently associated with HCC development and lower platelet levels at baseline. Baseline cirrhosis was not independently associated with any type of mortality. Compared with the general population, in all CHB patients mortality was not significantly different (SMR 0.82), whereas it was lower in patients without HCC regardless of baseline cirrhosis (SMR 0.58) and was higher in patients who developed HCC (SMR 3.09). CONCLUSION: Caucasian patients with CHB and compensated liver disease who receive long-term entecavir/tenofovir therapy have excellent overall and liver-related eight-year survival, which is similar to that of the general population. HCC is the main factor affecting their overall mortality, and is the only factor affecting their liver-related mortality. LAY SUMMARY: Caucasian patients with chronic hepatitis B with or without compensated cirrhosis who receive long-term entecavir or tenofovir therapy have excellent overall eight-year survival, which is similar to that of the general population. Hepatocellular carcinoma is the main factor affecting their overall mortality, and is the only factor affecting liver-related mortality in this setting.
Fibrosis is the extensive accumulation and buildup of extracellular matrix components, especially fibrillar collagens, during wound healing in response to tissue injury. During all individual stages of fibrosis ECM proteases, mainly matrix metalloproteinases, have diverse roles. The functional role of MMPs and their endogenous inhibitors are differentiated among their family members, and according to the different stages of fibrosis. MMPs levels are elevated in several inflammatory and non-inflammatory fibrotic tissues contributing to the development, progression or resolution of the disease, whereas in other tissues their expression levels can be diminished or be stable to the baseline. The biological roles of MMPs during fibrosis are not fully resolved, but they seem to differ according the specific member of the family, the affected tissue and the stage of the fibrotic response. Remarkably, some members of the family exhibit profibrotic actions while other function as antifibrotic molecules. Diverse animal models indicate that MMPs are contributing in processes related to immunity, tissue repair and ECM turnover, providing significant impact on mechanisms related to fibrosis. For that purpose, these proteases are considered as pharmacological targets and new biological drugs have been developed in order to treat fibrosis.
A deterministic seismic risk and monetary loss model is presented for the capital of Santorini volcanic Island, the town of Fira, on a building block scale. A local seismic source of M5.6 inferred from a recent volcano unrest in 2011–2012, detailed seismic vulnerability of 435 buildings and site conditions deduced from free-field ambient noise measurements were combined toward assessing the EMS-98 damage grade and its probability to occur. The seismic scenario yielded no damage or slight damage for 84{%} of the buildings, 16{%} of the constructions are expected to present moderate-to-heavy damage, while the economic loss amounts to 4 million euros. Although the model predicts low damage and direct economic loss, interaction with the touristic business activities might produce cascade side effects for the economy of the island and consequently Greece's GDP, an important part of which emanates from Santorini.
This paper discusses a new method for encoding ByzantineMusic Neumatic Notation (especially the one developedduring the ‘transitory’ period 1670-1814). The Notation ofthis period is characterized by difficulties and peculiarities.The difficult access to Byzantine manuscripts and their deterioratedcondition, complicate reading. In addition, our incompleteknowledge of the interpretation of signs impedesthe comprehension of the musical text leading in results thatare often in dispute. The fact that sign unions are complexenough together with their presence in various places ina composition make electronic transcriptions the ultimatechallenge. Moreover, there does not exist a framework fordata encoding and analysis. This work presents a proposalfor the development of such a model for the old ByzantineNeumatic Notation in Python. The implementation of thisproject is still at an initial stage, and focuses, mostly, on theefficient digitization of old manuscripts. The system, eventhough fully functional, has certain limitations. Some signsare missing, and the musical text is created using microphotographies.Future developments of the program will focuson resolving these deficiencies and adding more features tothe system.
The current paper presents the students' evaluation of a laboratory e-learning course in Health Informatics. After attending the e-learning course, students assessed the e-learning course through an anonymous questionnaire. The study results present the positive attitude of the students towards the e-learning course in Health Informatics. The current e-learning course is easy to use, and it is preferred on the same extent as the hybrid one (e-learning and in-class learning combination). The majority of the participants believed that the e-learning method is at least the same or more efficient compared to the traditional learning approach. Based on the study findings, it seems that this e-learning course could offer important advantages on the learning process as long as it helps students learn in a more effective manner than traditional learning.
Cerebral cortex size differs dramatically between reptiles, birds, and mammals, owing to developmental differences in neuron production. In mammals, signaling pathways regulating neurogenesis have been identified, but genetic differences behind their evolution across amniotes remain unknown. We show that direct neurogenesis from radial glia cells, with limited neuron production, dominates the avian, reptilian, and mammalian paleocortex, whereas in the evolutionarily recent mammalian neocortex, most neurogenesis is indirect via basal progenitors. Gain- and loss-of-function experiments in mouse, chick, and snake embryos and in human cerebral organoids demonstrate that high Slit/Robo and low Dll1 signaling, via Jag1 and Jag2, are necessary and sufficient to drive direct neurogenesis. Attenuating Robo signaling and enhancing Dll1 in snakes and birds recapitulates the formation of basal progenitors and promotes indirect neurogenesis. Our study identifies modulation in activity levels of conserved signaling pathways as a primary mechanism driving the expansion and increased complexity of the mammalian neocortex during amniote evolution.
Frequency-dependent brightness fluctuations of radio sources, the so-called extreme scattering events (ESEs), have been observed over the last three decades. They are caused by Galactic plasma structures whose geometry and origin are still poorly understood. In this paper, we construct axisymmentric two-dimensional (2D) column density profiles for the plasma lens and explore the resulting ESEs for both point-like and extended sources. A quantity that becomes relevant is the impact parameter b, namely the distance of the observer's path from the lens' symmetry axis. We demonstrate its effects on the shape of ESE light curves and use it for a phenomenological classification of ESEs into four main types. Three of them are unique outcomes of the 2D model and do not show a characteristic U-shaped dip in the light curve, which has been traditionally used as an identification means of ESEs. We apply our model to five well-studied ESEs and show that elongated plasma tubes or quasi-spherical clouds are favoured over plasma sheets for four of them, while the remaining one is compatible with both lens geometries.
The role of extended lymphadenectomy in the surgical treatment of gastric cancer has been debated for many years. So far six prospective randomized trials and a number of meta-analyses comparing D- to D-lymphadenectomy in open surgery have been published with contradicting results. The possible oncologic benefit of radical lymphadenectomy has been blurred by a number of reasons. In most of the trials the strategies under comparison were made similar after protocol violations. Imperfect design of the trials could not exclude the influence of cofounding factors. Inappropriate endpoints could not detect evidently the difference between the two surgical strategies. On the other hand radical lymphadenectomy was characterized by increased morbidity and mortality. This was mostly caused by the addition of pancreatico-splenectomy in all D-dissections, even when not indicated. A careful analysis of the available evidence indicates that D-lymphadenectomy performed by adequately trained surgeons without resection of the pancreas and/or spleen, unless otherwise indicated, decreases Gastric Cancer Related Deaths and increases Disease Specific Survival. This evidence is not compelling but cannot be ignored. D-lymphadendctomy is nowadays considered to be the standard of care for resectable gastric cancer.
A number of environmental pollutants and endogenous oxidation agents form 1-(2-deoxy-β-D-ribofura- nosyl)-5-hydroxy-5-methylhydantoin (HydT), an important DNA lesion resulting from thymidine oxi- dation. In this paper, two intermediates, postulated in the formation of HydT, have been characterised for the first time. The first, N1-formyl-N3-pyruvoylurea intermediate, was produced by the ozonolysis reaction of 2’,3’,5’-tri-O-acetylribo-, 3’,5’-di-O-TBS- and N3,O3’,O5-tribenzyl-protected thymidines and was shown to produce, upon decomposition and depending on the protecting group and the conditions, HydT alone, or together with protected-β-D-ribofuranosyl-N1-formylurea and formamide products. In addition, the second and long sought, open-chain-pyruvoylurea intermediate, was produced through de novo synthesis in protected β-D-ribofuranosyl-, 2-deoxy-β-D-ribofuranosyl- and 2-deoxy-β-D-ribo- pyranosyl systems. The conditions that induce the cyclization to the hydantoin ring of HydT have been determined. The chemistry utilised in the de novo synthesis is suitable for generating isotopically labelled HydT, as a reference in isotope-dilution-aided quantification of DNA damage.
We are witnessing the birth of a new variety of pharmacokinetics where non-integer-order differential equations are employed to study the time course of drugs in the body: this is dubbed ``fractional pharmacokinetics{''}. The presence of fractional kinetics has important clinical implications such as the lack of a half-life, observed, for example with the drug amiodarone and the associated irregular accumulation patterns following constant and multiple-dose administration. Building models that accurately reflect this behaviour is essential for the design of less toxic and more effective drug administration protocols and devices. This article introduces the readers to the theory of fractional pharmacokinetics and the research challenges that arise. After a short introduction to the concepts of fractional calculus, and the main applications that have appeared in literature up to date, we address two important aspects. First, numerical methods that allow us to simulate fractional order systems accurately and second, optimal control methodologies that can be used to design dosing regimens to individuals and populations.
Context. The second Gaia data release (Gaia DR2) contains high-precision positions, parallaxes, and proper motions for 1.3 billion sources as well as line-of-sight velocities for 7.2 million stars brighter than GRVS = 12 mag. Both samples provide a full sky coverage. Aims: To illustrate the potential of Gaia DR2, we provide a first look at the kinematics of the Milky Way disc, within a radius of several kiloparsecs around the Sun. Methods: We benefit for the first time from a sample of 6.4 million F-G-K stars with full 6D phase-space coordinates, precise parallaxes (σϖ/ϖ ≤ 20%), and precise Galactic cylindrical velocities (median uncertainties of 0.9-1.4 km s-1 and 20% of the stars with uncertainties smaller than 1 km s-1 on all three components). From this sample, we extracted a sub-sample of 3.2 million giant stars to map the velocity field of the Galactic disc from 5 kpc to 13 kpc from the Galactic centre and up to 2 kpc above and below the plane. We also study the distribution of 0.3 million solar neighbourhood stars (r < 200 pc), with median velocity uncertainties of 0.4 km s-1, in velocity space and use the full sample to examine how the over-densities evolve in more distant regions. Results: Gaia DR2 allows us to draw 3D maps of the Galactocentric median velocities and velocity dispersions with unprecedented accuracy, precision, and spatial resolution. The maps show the complexity and richness of the velocity field of the galactic disc. We observe streaming motions in all the components of the velocities as well as patterns in the velocity dispersions. For example, we confirm the previously reported negative and positive galactocentric radial velocity gradients in the inner and outer disc, respectively. Here, we see them as part of a non-axisymmetric kinematic oscillation, and we map its azimuthal and vertical behaviour. We also witness a new global arrangement of stars in the velocity plane of the solar neighbourhood and in distant regions in which stars are organised in thin substructures with the shape of circular arches that are oriented approximately along the horizontal direction in the U - V plane. Moreover, in distant regions, we see variations in the velocity substructures more clearly than ever before, in particular, variations in the velocity of the Hercules stream. Conclusions: Gaia DR2 provides the largest existing full 6D phase-space coordinates catalogue. It also vastly increases the number of available distances and transverse velocities with respect to Gaia DR1. Gaia DR2 offers a great wealth of information on the Milky Way and reveals clear non-axisymmetric kinematic signatures within the Galactic disc, for instance. It is now up to the astronomical community to explore its full potential.
Context. Gaia Data Release 2 provides high-precision astrometry and three-band photometry for about 1.3 billion sources over the full sky. The precision, accuracy, and homogeneity of both astrometry and photometry are unprecedented. Aims: We highlight the power of the Gaia DR2 in studying many fine structures of the Hertzsprung-Russell diagram (HRD). Gaia allows us to present many different HRDs, depending in particular on stellar population selections. We do not aim here for completeness in terms of types of stars or stellar evolutionary aspects. Instead, we have chosen several illustrative examples. Methods: We describe some of the selections that can be made in Gaia DR2 to highlight the main structures of the Gaia HRDs. We select both field and cluster (open and globular) stars, compare the observations with previous classifications and with stellar evolutionary tracks, and we present variations of the Gaia HRD with age, metallicity, and kinematics. Late stages of stellar evolution such as hot subdwarfs, post-AGB stars, planetary nebulae, and white dwarfs are also analysed, as well as low-mass brown dwarf objects. Results: The Gaia HRDs are unprecedented in both precision and coverage of the various Milky Way stellar populations and stellar evolutionary phases. Many fine structures of the HRDs are presented. The clear split of the white dwarf sequence into hydrogen and helium white dwarfs is presented for the first time in an HRD. The relation between kinematics and the HRD is nicely illustrated. Two different populations in a classical kinematic selection of the halo are unambiguously identified in the HRD. Membership and mean parameters for a selected list of open clusters are provided. They allow drawing very detailed cluster sequences, highlighting fine structures, and providing extremely precise empirical isochrones that will lead to more insight in stellar physics. Conclusions: Gaia DR2 demonstrates the potential of combining precise astrometry and photometry for large samples for studies in stellar evolution and stellar population and opens an entire new area for HRD-based studies. The full Table A.1 is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/616/A10
Context. The Gaia spacecraft of the European Space Agency (ESA) has been securing observations of solar system objects (SSOs) since the beginning of its operations. Data Release 2 (DR2) contains the observations of a selected sample of 14,099 SSOs. These asteroids have been already identified and have been numbered by the Minor Planet Center repository. Positions are provided for each Gaia observation at CCD level. As additional information, complementary to astrometry, the apparent brightness of SSOs in the unfiltered G band is also provided for selected observations. Aims: We explain the processing of SSO data, and describe the criteria we used to select the sample published in Gaia DR2. We then explore the data set to assess its quality. Methods: To exploit the main data product for the solar system in Gaia DR2, which is the epoch astrometry of asteroids, it is necessary to take into account the unusual properties of the uncertainty, as the position information is nearly one-dimensional. When this aspect is handled appropriately, an orbit fit can be obtained with post-fit residuals that are overall consistent with the a-priori error model that was used to define individual values of the astrometric uncertainty. The role of both random and systematic errors is described. The distribution of residuals allowed us to identify possible contaminants in the data set (such as stars). Photometry in the G band was compared to computed values from reference asteroid shapes and to the flux registered at the corresponding epochs by the red and blue photometers (RP and BP). Results: The overall astrometric performance is close to the expectations, with an optimal range of brightness G 12 - 17. In this range, the typical transit-level accuracy is well below 1 mas. For fainter asteroids, the growing photon noise deteriorates the performance. Asteroids brighter than G 12 are affected by a lower performance of the processing of their signals. The dramatic improvement brought by Gaia DR2 astrometry of SSOs is demonstrated by comparisons to the archive data and by preliminary tests on the detection of subtle non-gravitational effects.
Context. We present the second Gaia data release, Gaia DR2, consisting of astrometry, photometry, radial velocities, and information on astrophysical parameters and variability, for sources brighter than magnitude 21. In addition epoch astrometry and photometry are provided for a modest sample of minor planets in the solar system. Aims: A summary of the contents of Gaia DR2 is presented, accompanied by a discussion on the differences with respect to Gaia DR1 and an overview of the main limitations which are still present in the survey. Recommendations are made on the responsible use of Gaia DR2 results. Methods: The raw data collected with the Gaia instruments during the first 22 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into this second data release, which represents a major advance with respect to Gaia DR1 in terms of completeness, performance, and richness of the data products. Results: Gaia DR2 contains celestial positions and the apparent brightness in G for approximately 1.7 billion sources. For 1.3 billion of those sources, parallaxes and proper motions are in addition available. The sample of sources for which variability information is provided is expanded to 0.5 million stars. This data release contains four new elements: broad-band colour information in the form of the apparent brightness in the GBP (330-680 nm) and GRP (630-1050 nm) bands is available for 1.4 billion sources; median radial velocities for some 7 million sources are presented; for between 77 and 161 million sources estimates are provided of the stellar effective temperature, extinction, reddening, and radius and luminosity; and for a pre-selected list of 14 000 minor planets in the solar system epoch astrometry and photometry are presented. Finally, Gaia DR2 also represents a new materialisation of the celestial reference frame in the optical, the Gaia-CRF2, which is the first optical reference frame based solely on extragalactic sources. There are notable changes in the photometric system and the catalogue source list with respect to Gaia DR1, and we stress the need to consider the two data releases as independent. Conclusions: Gaia DR2 represents a major achievement for the Gaia mission, delivering on the long standing promise to provide parallaxes and proper motions for over 1 billion stars, and representing a first step in the availability of complementary radial velocity and source astrophysical information for a sample of stars in the Gaia survey which covers a very substantial fraction of the volume of our galaxy.
Context. The second release of Gaia data (Gaia DR2) contains the astrometric parameters for more than half a million quasars. This set defines a kinematically non-rotating reference frame in the optical domain. A subset of these quasars have accurate VLBI positions that allow the axes of the reference frame to be aligned with the International Celestial Reference System (ICRF) radio frame. Aims: We describe the astrometric and photometric properties of the quasars that were selected to represent the celestial reference frame of Gaia DR2 (Gaia-CRF2), and to compare the optical and radio positions for sources with accurate VLBI positions. Methods: Descriptive statistics are used to characterise the overall properties of the quasar sample. Residual rotation and orientation errors and large-scale systematics are quantified by means of expansions in vector spherical harmonics. Positional differences are calculated relative to a prototype version of the forthcoming ICRF3. Results: Gaia-CRF2 consists of the positions of a sample of 556 869 sources in Gaia DR2, obtained from a positional cross-match with the ICRF3-prototype and AllWISE AGN catalogues. The sample constitutes a clean, dense, and homogeneous set of extragalactic point sources in the magnitude range G ≃ 16 to 21 mag with accurately known optical positions. The median positional uncertainty is 0.12 mas for G < 18 mag and 0.5 mas at G = mag. Large-scale systematics are estimated to be in the range 20 to 30 μas. The accuracy claims are supported by the parallaxes and proper motions of the quasars in Gaia DR2. The optical positions for a subset of 2820 sources in common with the ICRF3-prototype show very good overall agreement with the radio positions, but several tens of sources have significantly discrepant positions. Conclusions: Based on less than 40% of the data expected from the nominal Gaia mission, Gaia-CRF2 is the first realisation of a non-rotating global optical reference frame that meets the ICRS prescriptions, meaning that it is built only on extragalactic sources. Its accuracy matches the current radio frame of the ICRF, but the density of sources in all parts of the sky is much higher, except along the Galactic equator.
The littoral region of Alexandria, east of Silsileh (the eastern promontory of the Eastern
Harbor) to Montazah promontory was investigated combining archaeological and geomorphological evidence in order to better understand the subsidence of the coastal zone. The coastal zone is rich in archaeological and geomorphological features able to provide insights into the evolution of the coastline and the relative sea level changes. Our study has revealed a continuous subsidence of the coastal zone, owed to various contributing processes, while further research is required to decipher the coastal evolution of this littoral.
Fluvial geomorphology is affected by physical conditions which allow its adaptation due to high dynamics and environmental influences. Fluvial morphological changes are manifested as a result of tendency of the river system to maintain its physical balance. Our study area is the upper and middle flow part of Vouraikos river and surrounding area, near the NW border of Chelmos mountain in Northern Peloponnese, near the town of Kalavrita, at an altitude of 800 m. The area is part of the Skepasto basin, constituting of a graben with a general E-W direction that was developed NW of Kalavrita. The area comprises of Mesozoic, Upper Triassic-Jurassic limestone and dolomite of the Tripolitsa unit External Hellenides and Plio-Pleistocene fluvio-lacustrine sequences, while its tectonic structure is characterized mainly by normal faults. The geomorphological landscape is characterized by alluvial deposits and important geomorphological features including fluvial terraces, alluvial fans, fluvial scarps and their main rill washes. This area has been a place of major human activity as shown by the findings of many uncovered artifacts and a settlement. Through a paleographic reconstruction, detailed field investigations, in combination with the compilation of geomorphological maps using GIS software and archaeological evidence found in the area, we attempted to reconstruct the fluvial evolution of Vouraikos river and identify the major geomorphological factors that led to, and influenced it. Finally, the link between cultural activities and sedimentary processes is also studied. The recorded environmental variations had a great impact on the geomorphological shaping and instability of Kalavrita plain and Vouraikos river and are being reflected on the buried settlement. Sediment fluxes were high enough to form strath terraces, while local tectonics aided in the strath and fill terrace creation. Smaller and younger strath terraces, formed during increased sediment supply periods, when the valley was at a higher level.
Vein-type Pb-Ni-Bi-Au-Ag mineralization at the Clemence deposit in the Kamariza and “km3” in the Lavrion area, was synchronous with the intrusion of a Miocene granodiorite body and related felsic and mafic dikes and sills within marbles and schists in the footwall of (and within) the Western Cycladic detachment system. In the Serpieri deposit (Kamariza area), a porphyry-style pyrrhotite-arsenopyrite mineralized microgranitic dike is genetically related to a garnet-wollastonite bearing skarn characterized by a similar base metal and Ni (up to 219 ppm) enrichment. The Ni–Bi–Au association in the Clemence deposit consists of initial deposition of pyrite and arsenopyrite followed by an intergrowth of native gold-bismuthinite and oscillatory zoned gersdorffite. The zoning is related to variable As, Ni, and Fe contents, indicating fluctuations of arsenic and sulfur fugacity in the hydrothermal fluid. A late evolution towards higher sulfur fugacity in the mineralization is evident by the deposition of chalcopyrite, tennantite, enargite, and galena rimming gersdorffite. At the “km3” locality, Ni sulfides and sulfarsenides, vaesite, millerite, ullmannite, and polydymite, are enclosed in gersdorffite and/or galena. The gersdorffite is homogenous and contains less Fe (up to 2 wt.%) than that from the Clemence deposit (up to 9 wt.%). Bulk ore analyses of the Clemence ore reveal Au and Ag grades both exceeding 100 g/t, Pb and Zn > 1 wt.%, Ni up to 9700 ppm, Co up to 118 ppm, Sn > 100 ppm, and Bi > 2000 ppm. The “km3” mineralization is enriched in Mo (up to 36 ppm), Ni (>1 wt.%), and Co (up to 1290 ppm). Our data further support a magmatic contribution to the ore-forming fluids, although remobilization and leaching of metals from previous mineralization and/or host rocks, through the late involvement of non-magmatic fluid in the ore system, cannot be excluded.
The Mesio-Temporal Lobe Epilepsy syndrome is the most common form of intractable epilepsy. It is characterized by recurrence of focal seizures and is often associated with hippocampal sclerosis and drug resistance. We aimed to characterize the molecular changes occurring during the initial stages of epileptogenesis in search of new therapeutic targets for Mesio-Temporal Lobe Epilepsy. We used a mouse model obtained by intra-hippocampal microinjection of kainate and performed hippocampal whole genome expression analysis at 6h, 12h and 24h post-injection, followed by multilevel bioinformatics analysis. We report significant changes in immune and inflammatory responses, neuronal network reorganization processes and glial functions, predominantly initiated during status epilepticus at 12h and persistent after the end of status epilepticus at 24h post-kainate. Upstream regulator analysis highlighted Cyba, Cybb and Vim as central regulators of multiple overexpressed genes implicated in glial responses at 24h. In silico microRNA analysis indicated that miR-9, miR-19b, miR-129, and miR-223 may regulate the expression of glial-associated genes at 24h. Our data support the hypothesis that glial-mediated inflammatory response holds a key role during epileptogenesis, and that microglial cells may participate in the initial process of epileptogenesis through increased ROS production via the NOX complex.
This paper investigates the spread of the Global Financial Crisis (GFC) and the Eurozone Sovereign Debt Crisis (ESDC) to different market capitalization segments across countries and regions. Specifically, it tests for capitalization-specific contagion across both crises and their phases by examining large, medium and small capitalization indices of G-20 equity markets. The analysis across stable and the two crisis periods shows the existence of a stronger largecap transmission channel for the majority of countries. On the other hand, the contagion dynamics across the phases of the two crises do not provide a clear pattern of a specific cap size-based contagion across all markets. However, there is evidence that the Pacific region and the three cap groups of some individual markets of different regions are less severely affected. Further, all three cap groups of developed markets are mostly affected during the last phase of the ESDC, while emerging and frontier markets show a more diverse pattern of contagion across the phases of both crises. Finally, the Lehman Brothers’ collapse triggers a dramatic increase of the infection rate, while the ESDC seems to be more contagious than the GFC.
Bidwell PA, Liu GS, Nagarajan N, Lam CK, Haghighi K, Gardner G, Cai WF, Zhao W, Mugge L, Vafiadaki E, et al.HAX-1 regulates SERCA2a oxidation and degradation. J Mol Cell CardiolJ Mol Cell CardiolJ Mol Cell Cardiol. 2018;114:220-233.Abstract
Ischemia/reperfusion injury is associated with contractile dysfunction and increased cardiomyocyte death. Overexpression of the hematopoietic lineage substrate-1-associated protein X-1 (HAX-1) has been shown to protect from cellular injury but the function of endogenous HAX-1 remains obscure due to early lethality of the knockout mouse. Herein we generated a cardiac-specific and inducible HAX-1 deficient model, which uncovered an unexpected role of HAX-1 in regulation of sarco/endoplasmic reticulum Ca-ATPase (SERCA2a) in ischemia/reperfusion injury. Although ablation of HAX-1 in the adult heart elicited no morphological alterations under non-stress conditions, it diminished contractile recovery and increased infarct size upon ischemia/reperfusion injury. These detrimental effects were associated with increased loss of SERCA2a. Enhanced SERCA2a degradation was not due to alterations in calpain and calpastatin levels or calpain activity. Conversely, HAX-1 overexpression improved contractile recovery and maintained SERCA2a levels. The regulatory effects of HAX-1 on SERCA2a degradation were observed at multiple levels, including intact hearts, isolated cardiomyocytes and sarcoplasmic reticulum microsomes. Mechanistically, HAX-1 ablation elicited increased production of reactive oxygen species at the sarco/endoplasic reticulum compartment, resulting in SERCA2a oxidation and a predisposition to its proteolysis. This effect may be mediated by NAPDH oxidase 4 (NOX4), a novel binding partner of HAX-1. Accordingly, NOX inhibition with apocynin abrogated the effects of HAX-1 ablation in hearts subjected to ischemia/reperfusion injury. Taken together, our findings reveal a role of HAX-1 in the regulation of oxidative stress and SERCA2a degradation, implicating its importance in calcium homeostasis and cell survival pathways.
BACKGROUND: Elimination of hepatitis C virus (HCV) among people who inject drugs (PWID) is a costly investment, so strategies should not only focus on eliminating the disease, but also on preventing disease resurgence. The aims of this study are to compute the minimum necessary antiviral therapies to achieve elimination with and without the additional expansion of harm reduction (HR) programs and to examine the sustainability of HCV elimination after 2030 if treatment is discontinued. METHOD: We considered two types of epidemic (with low (30%) and high (50%) proportion of PWID who engage in sharing equipment (sharers)) within three baseline chronic HCV (CHC) prevalence settings (30%, 45% and 60%), assuming a baseline HR coverage of 40%. We define sustainable elimination strategies, those that could maintain eliminations results for a decade (2031-2040), in the absence of additional treatment. RESULTS: The model shows that the optimum elimination strategy is dependent on risk sharing behavior of the examined population. The necessary annual treatment coverage to achieve HCV elimination under 45% baseline CHC prevalence, without the simultaneous expansion of HR programs, ranges between 4.7-5.1%. Similarly, under 60% baseline CHC prevalence the needed treatment coverage varies from 9.0-10.5%. Increasing HR coverage from 40% to 75%, reduces the required treatment coverage by 6.5-9.8% and 11.0-15.0% under 45% or 60% CHC prevalence, respectively. In settings with
BACKGROUND: High Density Lipoprotein (HDL) and its main protein component, apolipoprotein A-I (apoA-I), have numerous atheroprotective functions on various tissues including the endothelium. Therapies based on reconstituted HDL containing apoA-I (rHDL-apoA-I) have been used successfully in patients with acute coronary syndrome, peripheral vascular disease or diabetes but very little is known about the genomic effects of rHDL-apoA-I and how they could contribute to atheroprotection. OBJECTIVE: The present study aimed to understand the endothelial signaling pathways and the genes that may contribute to rHDL-apoA-I-mediated atheroprotection. METHODS: Human aortic endothelial cells (HAECs) were treated with rHDL-apoA-I and their total RNA was analyzed with whole genome microarrays. Validation of microarray data was performed using multiplex RT-qPCR. The expression of ANGPTL4 in EA.hy926 endothelial cells was determined by RT-qPCR and Western blotting. The contribution of signaling kinases and transcription factors in ANGPTL4 gene regulation by HDL-apoA-I was assessed by RT-qPCR, Western blotting and immunofluorescence using chemical inhibitors or siRNA-mediated gene silencing. RESULTS: It was found that 410 transcripts were significantly changed in the presence of rHDL-apoA-I and that angiopoietin like 4 (ANGPTL4) was one of the most upregulated and biologically relevant molecules. In validation experiments rHDL-apoA-I, as well as natural HDL from human healthy donors or from transgenic mice overexpressing human apoA-I (TgHDL-apoA-I), increased ANGPTL4 mRNA and protein levels. ANGPTL4 gene induction by HDL was direct and was blocked in the presence of inhibitors for the AKT or the p38 MAP kinases. TgHDL-apoA-I caused phosphorylation of the transcription factor forkhead box O1 (FOXO1) and its translocation from the nucleus to the cytoplasm. Importantly, a FOXO1 inhibitor or a FOXO1-specific siRNA enhanced ANGPTL4 expression, whereas administration of TgHDL-apoA-I in the presence of the FOXO1 inhibitor or the FOXO1-specific siRNA did not induce further ANGPTL4 expression. These data suggest that FOXO1 functions as an inhibitor of ANGPTL4, while HDL-apoA-I blocks FOXO1 activity and induces ANGPTL4 through the activation of AKT. CONCLUSION: Our data provide novel insights into the global molecular effects of HDL-apoA-I on endothelial cells and identify ANGPTL4 as a putative mediator of the atheroprotective functions of HDL-apoA-I on the artery wall, with notable therapeutic potential.
Blazar OJ287 exhibits large thermal flares at least twice every 12 years. The times of these flares have been predicted successfully using the model of a quasi-Keplerian eccentric black hole binary where the secondary impacts the accretion disk of the primary, creating the thermal flares. New measurements of the historical light curve have been combined with the observations of the 2015 November/December flare to identify the impact record since year 1886, and to constrain the orbit of the binary. The orbital solution shows that the binary period, now 12.062 years, is decreasing at the rate of 36 days per century. This corresponds to an energy loss to gravitational waves that is 6.5 +/- 4 % less than the rate predicted by the standard quadrupolar gravitational wave (GW) emission. We show that the difference is due to higher order gravitational radiation reaction terms that include the dominant order tail contributions.
The effects of high intensity interval training (HIIT) frequency on cardiometabolic health and quality of life were examined in 35 healthy inactive adults (age: 31.7±2.6 yrs, VOpeak: 32.7±7.4 ml·: kg ·: min). Participants were randomly assigned to a control (CON) and two training groups, which performed 10×60-s cycling at ~83% of peak power, two (HIIT-2) or three times per week (HIIT-3) for eight weeks. Compared with CON, both training regimes resulted in similar improvements in VOpeak (HIIT-2: 10.8%, p=0.048, HIIT-3: 13.6%, p=0.017), waist circumference (HIIT-2: -1.4 cm, p=0.048, HIIT-3: -2.4 cm, p=0.028), thigh cross-sectional area (HIIT-2: 11.4 cm, p=0.001, HIIT-3: 9.3 cm, p=0.001) and the physical health component of quality of life (HIIT-2: 8.4, p=0.001, HIIT-3: 12.2, p=0.001). However, HIIT-3 conferred additional health-related benefits by reducing total body and trunk fat percentage (p<0.05, compared with CON), total cholesterol and low-density lipoprotein-cholesterol (p<0.02, compared with CON) and by improving the mental component of quality of life (p=0.045, compared with CON). In conclusion, performing HIIT only twice per week is effective in promoting cardiometabolic health-related adaptations and quality of life in inactive adults. However, higher HIIT frequency is required for an effect on fat deposits, cholesterol and mental component of well-being.
Sudden unexpected cardiac death (SCD) accounts for up to half of all-cause mortality of heart failure patients. Standardized cardiology tools such as electrocardiography, cardiac imaging, electrophysiological and serum biomarkers cannot accurately predict which patients are at risk of life-threatening arrhythmic episodes. Recently, a common variant of the histidine-rich calcium binding protein (HRC), the Ser96Ala, was identified as a potent biomarker of malignant arrhythmia triggering in these patients. HRC has been shown to be involved in the regulation of cardiac sarcoplasmic reticulum (SR) Ca(2+) cycling, by binding and storing Ca(2+) in the SR, as well as interacting with the SR Ca(2+) uptake and release complexes. The underlying mechanisms, elucidated by studies at the molecular, biochemical, cellular and intact animal levels, indicate that transversion of Ser96 to Ala results in abolishment of an HRC phosphorylation site by Fam20C kinase and dysregulation of SR Ca(2+) cycling. This is mediated through aberrant SR Ca(2+) release by the ryanodine receptor (RyR2) quaternary complex, due to the impaired HRC/triadin interaction, and depressed SR Ca(2+) uptake by the sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA2) pump, due to the impaired HRC/SERCA2 interaction. Pharmacological intervention with KN-93, an inhibitor of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), in the HRC Ser96Ala mouse model, reduced the occurrence of malignant cardiac arrhythmias. Herein, we summarize the current evidence on the pivotal role of HRC in the regulation of cardiac rhythmicity and the importance of HRC Ser96Ala as a genetic modifier for arrhythmias in the setting of heart failure.
Since HIV-1 treatment is increasingly considered an effective preventionstrategy, it is important to study local HIV-1 epidemics to formulate tailored preventionpolicies. The prevalence of HIV-1 in Cyprus was historically low until 2005. To investigatethe shift in epidemiological trends, we studied the transmission dynamics of HIV-1 in Cyprususing a densely sampled Cypriot HIV-1 transmission cohort that included 85 percent ofHIV-1-infected individuals linked to clinical care between 1986 and 2012 based on detailedclinical, epidemiological, behavioral and HIV-1 genetic information. Subtyping andtransmission cluster reconstruction were performed using maximum likelihood and Bayesianmethods, and the transmission chain network was linked to the clinical, epidemiological andbehavioral data. The results reveal that for the main HIV-1 subtype A1 and B sub-epidemics,young and drug-naïve HIV-1-infected individuals in Cyprus are driving the dynamics of thelocal HIV-1 epidemic. The results of this study provide a better understanding of thedynamics of the HIV-1 infection in Cyprus, which may impact the development of preventionstrategies. Furthermore, this methodology for analyzing densely sampled transmissiondynamics is applicable to other geographic regions to implement effective HIV-1 preventionstrategies in local settings.
A molecular epidemiology study of HIV-1 infection was conducted in one hundred diagnosed and untreated HIV-1-infected patients in Cyprus between 2010 and 2012, representing 65.4% of all the reported HIV-1 infections in Cyprus in this three-year period, using a previously defined enrolment strategy. Eighty-two patients were newly diagnosed (genotypic drug resistance testing within six months from diagnosis), and eighteen patients were HIV-1 diagnosed for a longer period or the diagnosis date was unknown. Phylogenetic trees of the pol sequences obtained in this study with reference sequences indicated that subtypes B and A1 were the most common subtypes present and accounted for 41.0 and 19.0% respectively, followed by subtype C (7.0%), F1 (8.0%), CRF02_AG (4.0%), A2 (2.0%), other circulating recombinant forms (CRFs) (7.0%) and unknown recombinant forms (URFs) (12%). Most of the newly-diagnosed study subjects were Cypriots (63%), males (78%) with median age 39 (Interquartile Range, IQR 33-48) reporting having sex with other men (MSM) (51%). A high rate of clustered transmission of subtype B drug-sensitive strains to reverse transcriptase and protease inhibitors was observed among MSM, twenty-eight out of forty-one MSM study subjects (68.0%) infected were implicated in five transmission clusters, two of which are sub-subtype A1 and three of which are subtype B strains. The two largest MSM subtype B clusters included nine and eight Cypriot men, respectively, living in all major cities in Cyprus. There were only three newly diagnosed patients with transmitted drug resistant HIV-1 strains, one study subject from the United Kingdom infected with subtype B strain and one from Romania with sub-subtype A2 strain, both with PI drug resistance mutation M46L and one from Greece with sub-subtype A1 with non-nucleoside reverse transcriptase inhibitors (NNRTI) drug resistance mutation K103N.
Koseoglou P, Werner V, Pietralla N, IKP TU, Bonatsos D. HNPS Proceedings. 2018.
This study examines the attitudes of 552 undergraduate heterosexual students—of the National and Kapodistrian University of Athens, the School of Physical Education and Sport Science—towards male and female homosexuality. The authors begin with an overview of the hegemonic gender order in sports, subsequently examining the factors/variables that determine homophobic attitudes in male and female heterosexual students. Initially, 577 physical education students were asked to participate: 25 declared they were non-heterosexual (homosexual and bisexual). The 552 students that agreed to continue completed a demographic questionnaire and Herek’s (1994) Attitudes Towards Lesbian and Gay Men
Scale (ATLG), specifically the Greek version (Grigoropoulos, Papacharitou, & Moraitou, 2010). The findings show that sport participation/engagement is not a factor that influences attitudes. The four factors that predict attitudes towards homosexuals are gender, religiosity, political leaning and socializing with a non-heterosexual. The results indicate that anti-homophobia strategies are required. Accordingly, the article concludes with recommendations and proposals for future research, arguing for the integration of a gender perspective—including unconscious bias training—diversity policies and monitoring processes in organisational and institutional structures to change attitudes, and eventually eliminate systemic discrimination directed at individuals or groups due to sexual orientation and gender identity.
Keywords : Gender, hegemonic masculinity, non-heterosexuals, sports, respect for diversity, Homophobia, homosexuality, gender attitudes, gender order, sport, physical education
Quality standards have been widely adopted in healthcare, while the Hospital Information Systems (HIS) support quality management in modern hospitals. However, staff compliance lags behind. In this study, we investigated the effect of a novel application, implemented in the HIS, on staff compliance in the Intensive Care Unit of a tertiary teaching hospital. This application integrates quality protocols to the HIS, which is routinely used by the nursing staff. Demographic data and self-reported compliance were recorded before and after the intervention. We found that the compliance rate was significantly increased and the application was well accepted by the majority of the staff. We also showed that previous ICU working experience is independently and positively associated with compliance (p=0.02, OR=2.86; 95% CI: 1.16 - 7.06), after adjustment for age and total nursing experience In conclusion, we developed an effective application for quality improvement aiming at facilitating educational processes and enhancing staff compliance.
The present study focuses on the profile of "endogeneous" caveolin-1 protein in septic lung (CLP model).Caveolin-1, CD25, pP38, pAkt, and 14-3-3b protein expression profiles were studied using flow cytometry and immunohistochemistry 6, 12, 24, 36, and 48 h after sepsis induction. Cell viability was determined by 7-AAD staining and fibrosis by Masson trichrome stain. The effect of protein C zymogen concentrate (PC) on caveolin-1 expression was also investigated given that PC, once dissociated from caveolin-1, elicits a PAR-1-mediated protective signaling by forming a complex with endothelial protein C receptor (EPCR).CLP treatment increased lung inflammation and cell apoptosis. Fibrosis was apparent in vessels and alveoli. Caveolin-1+ cells presented reduced protein expression, especially 12 h post-CLP (P = 0.002). Immunohistochemistry revealed caveolin-1 positive expression mainly in regions with strong inflammatory reaction. Early induction of pP38+ cell population (P = 0.014) and gradual increase of CD25+ cells were also observed. Alternations in 14-3-3b expression related to apoptosis were apparent and accompanied by increased AKT phosphorylation activity late during sepsis progression.After PC administration, cell apoptosis was reduced (P = 0.004) and both the percentile and expression intensity of caveolin-1 positive cells were compromised (P = 0.009 and P = 0.027, respectively). 14-3-3b, CD25, and pP38 protein expression were decreased (P = 0.014, P = 0.004, and P = 0.007, respectively), whereas pAkt expression was induced (P = 0.032).The observed decline of endogenous caveolin-1 protein expression during sepsis implies its involvement in host's cytoprotective reaction either directly, by controlling caveolae population to decrease bacterial burden, or indirectly via regulating 14-3-3b-dependent apoptosis and EPCR-PAR-1-dependent protective signaling.
HERV-K HML-2 (HK2) has been proliferating in the germ line of humans at least as recently as 250,000 years ago, with some integrations that remain polymorphic in the modern human population. One of the solitary HK2 LTR polymorphic integrations lies between exons 17 and 18 of RASGRF2, a gene that affects dopaminergic activity and is thus related to addiction. Here we show that this antisense HK2 integration (namely RASGRF2-int) is found more frequently in persons who inject drugs compared with the general population. In a Greek HIV-1-positive population (n = 202), we found RASGRF2-int 2.5 times (14 versus 6%) more frequently in patients infected through i.v. drug use compared with other transmission route controls (P = 0.03). Independently, in a United Kingdom-based hepatitis C virus-positive population (n = 184), we found RASGRF2-int 3.6 times (34 versus 9.5%) more frequently in patients infected during chronic drug abuse compared with controls (P < 0.001). We then tested whether RASGRF2-int could be mechanistically responsible for this association by modulating transcription of RASGRF2 We show that the CRISPR/Cas9-mediated insertion of HK2 in HEK293 cells in the exact RASGRF2 intronic position found in the population resulted in significant transcriptional and phenotypic changes. We also explored mechanistic features of other intronic HK2 integrations and show that HK2 LTRs can be responsible for generation of cis-natural antisense transcripts, which could interfere with the transcription of nearby genes. Our findings suggest that RASGRF2-int is a strong candidate for dopaminergic manipulation, and emphasize the importance of accurate mapping of neglected HERV polymorphisms in human genomic studies.
Interfaces are ubiquitous in materials science, and in devices in particular. As device dimensions are constantly shrinking, understanding the physical properties emerging at interfaces is crucial to exploit them for applications, here for spintronics. Using first-principles techniques and Monte Carlo simulations, we investigate the mutual magnetic interaction at the interface between graphene and an antiferromagnetic semiconductor BaMnO3. We find that graphene deeply affects the magnetic state of the substrate, down to several layers below the interface, by inducing an overall magnetic softening, and switching the in-plane magnetic ordering from antiferromagnetic to ferromagnetic. The graphene-BaMnO3 system presents a Rashba gap 300 times larger than in pristine graphene, leading to a flavor of quantum anomalous Hall effect (QAHE), a hybrid QAHE, characterized by the coexistence of metallic and topological insulating states. These findings could be exploited to fabricate devices that use graphene to control the magnetic configuration of a substrate.
PURPOSE:
Irisin, a newly discovered adipo-myokine, is implicated in the modulation of the adipose phenotype, increasing energy expenditure and ameliorating systemic metabolism. Our aim was to investigate circulating irisin in subclinical hypothyroidism (SH) and study its associations with cardiometabolic risk factors.
METHODS:
In a large case-control study, serum irisin, insulin resistance and lipid parameters, classic adipokines, inflammatory and hepatic biomarkers, and cardiovascular risk factors were determined in 120 consecutive patients with SH and 120 healthy controls matched on age, gender, and date of blood draw. Sixteen patients with SH received L-T4 treatment and, after 6 months, serum irisin and other biomarkers were assessed.
RESULTS:
SH cases exhibited significantly higher circulating irisin than controls (p < 0.001). In all participants, irisin was positively associated with TSH, anti-TG, HOMA-IR, C-peptide, lipid and inflammatory biomarkers, leptin, and cardiovascular risk factors, including Framigham score and apolipoprotein B/apolipoprotein A-I. Irisin was negatively correlated with adiponectin, HDL-C, and thyroid hormones. Serum irisin was independently associated with SH, above and beyond body mass index and cardiometabolic factors (p = 0.02). TSH was an independent predictor of circulating irisin (p = 0.003). L-T4 therapy did not reverse considerably the hyperirisinemic status in treated SH patients (p = 0.09).
CONCLUSIONS:
Irisin may represent an adipo-myokine counterbalancing a potential, gradual deterioration of lipid metabolism and insulin sensitivity in SH as well as reflecting a protective compensatory mechanism against oxidative muscle and thyroid cell stress. More mechanistic and prospective studies shedding light on the pathogenetic role of irisin in SH are needed to confirm and extend these data.
The Large Magellanic Cloud (LMC) currently hosts around 23 high-mass X-ray binaries (HMXBs) of which most are Be/X-ray binaries. The LMC XMM-Newton survey provided follow-up observations of previously known X-ray sources that were likely HMXBs, as well as identifying new HMXB candidates. In total, 19 candidate HMXBs were selected based on their X-ray hardness ratios. In this paper we present red and blue optical spectroscopy, obtained with Southern African Large Telescope and the South African Astronomical Observatory 1.9-m telescope, plus a timing analysis of the long-term optical light curves from OGLE to confirm the nature of these candidates. We find that nine of the candidates are new Be/X-ray binaries, substantially increasing the LMC Be/X-ray binary population. Furthermore, we present the optical properties of these new systems, both individually and as a group of all the BeXBs identified by the XMM-Newton survey of the LMC.
We report on the temporal analysis of NICER and Fermi/GBM observations of the new transient Swift J005139.2-721704 located in the SMC (ATel #12209, #12219) that resulted in its identification with the known X-ray pulsar XTE J0052-723 (SXP 4.78).
We report on the X-ray and optical properties of two high-mass X-ray binary systems located in the Large Magellanic Cloud (LMC). Based on the obtained optical spectra, we classify the massive companion as a supergiant star in both systems. Timing analysis of the X-ray events collected by XMM-Newton revealed the presence of coherent pulsations (spin period ∼2013 s) for XMMU J053108.3-690923 and fast flaring behaviour for XMMU J053320.8-684122. The X-ray spectra of both systems can be modelled sufficiently well by an absorbed power law, yielding hard spectra and high intrinsic absorption from the environment of the systems. Due to their combined X-ray and optical properties, we classify both systems as SgXRBs: the 19th confirmed X-ray pulsar and a probable supergiant fast X-ray transient in the LMC, the second such candidate outside our Galaxy.
BACKGROUND: HBsAg immune-escape mutations can favor HBV-transmission also in vaccinated individuals, promote immunosuppression-driven HBV-reactivation, and increase fitness of drug-resistant strains. Stop-codons can enhance HBV oncogenic-properties. Furthermore, as a consequence of the overlapping structure of HBV genome, some immune-escape mutations or stop-codons in HBsAg can derive from drug-resistance mutations in RT. This study is aimed at gaining insight in prevalence and characteristics of immune-associated escape mutations, and stop-codons in HBsAg in chronically HBV-infected patients experiencing nucleos(t)ide analogues (NA) in Europe. METHODS: This study analyzed 828 chronically HBV-infected European patients exposed to ≥ 1 NA, with detectable HBV-DNA and with an available HBsAg-sequence. The immune-associated escape mutations and the NA-induced immune-escape mutations sI195M, sI196S, and sE164D (resulting from drug-resistance mutation rtM204 V, rtM204I, and rtV173L) were retrieved from literature and examined. Mutations were defined as an aminoacid substitution with respect to a genotype A or D reference sequence. RESULTS: At least one immune-associated escape mutation was detected in 22.1% of patients with rising temporal-trend. By multivariable-analysis, genotype-D correlated with higher selection of ≥ 1 immune-associated escape mutation (OR[95%CI]:2.20[1.32-3.67], P = 0.002). In genotype-D, the presence of ≥ 1 immune-associated escape mutations was significantly higher in drug-exposed patients with drug-resistant strains than with wild-type virus (29.5% vs 20.3% P = 0.012). Result confirmed by analysing drug-naïve patients (29.5% vs 21.2%, P = 0.032). Strong correlation was observed between sP120T and rtM204I/V (P < 0.001), and their co-presence determined an increased HBV-DNA. At least one NA-induced immune-escape mutation occurred in 28.6% of patients, and their selection correlated with genotype-A (OR[95%CI]:2.03[1.32-3.10],P = 0.001). Finally, stop-codons are present in 8.4% of patients also at HBsAg-positions 172 and 182, described to enhance viral oncogenic-properties. CONCLUSIONS: Immune-escape mutations and stop-codons develop in a large fraction of NA-exposed patients from Europe. This may represent a potential threat for horizontal and vertical HBV transmission also to vaccinated persons, and fuel drug-resistance emergence.
Hepatitis B virus (HBV) infection, a global public health problem can be asymptomatic, acute or chronic and can lead to serious consequences of infection, including cirrhosis, and hepatocellular carcinoma. HBV, a partially double stranded DNA virus, belongs to the family Hepadnaviridae, and replicates via reverse transcription of an RNA intermediate. This reverse transcription is catalyzed by a virus-encoded polymerase that lacks proof reading ability, which leads to sequence heterogeneity. HBV is classified into nine genotypes and at least 35 subgenotypes, which may be characterized by distinct geographical distributions. This HBV diversification and distinct geographical distribution has been proposed to be the result of the co-expansion of HBV with modern humans, after their out-of-Africa migration. HBeAg is a non-particulate protein of HBV that has immunomodulatory properties as a tolerogen that allows the virus to establish HBV infection in vivo. During the natural course of infection, there is seroconversion from a HBeAg-positive phase to a HBeAg-negative, anti-HBe-positive phase. During this seroconversion, there is loss of tolerance to infection and immune escape-HBeAg-negative mutants can be selected in response to the host immune response. The different genotypes and, in some cases, subgenotypes develop different mutations that can affect HBeAg expression at the transcriptional, translational and post-translational levels. The ability to develop mutations, affecting HBeAg expression, can influence the length of the HBeAg-positive phase, which is important in determining both the mode of transmission and the clinical course of HBV infection. Thus, the different genotypes/subgenotypes have evolved in such a way that they exhibit different modes of transmission and clinical manifestation of infection. Loss of HBeAg may be a sign of short-sighted evolution because there is loss of tolerogenic ability of HBeAg and HBeAg-negative virions are less transmissible. Depending on their ability to lead to HBeAg seroconversion, the genotype/subgenotypes exhibit varying degrees of short-sighted evolution. The "arms race" between HBV and the immune response to HBeAg is multifaceted and its elucidation intricate, with transmissibility and persistence being important for the survival of the virus. We attempt to shed some light on this complex interplay between host and virus.
BACKGROUND AND AIMS: Genetic polymorphisms within the promoter of interferon-α receptor type-1 (IFNAR1) have been associated with the susceptibility to and the outcome of chronic hepatitis B virus (HBV) infection. However, the impact of these polymorphisms in the transcriptome of the HBV-associated hepatocellular carcinoma (HCC) remains largely unexplored. METHODS: Using whole-genome and exome sequencing data from The Cancer Genome Atlas project, we characterized three single-nucleotide polymorphisms (SNPs: -568G/C, -408C/T, -3C/T) and one variable number tandem repeat [VNTR: -77(GT)n] within the IFNAR1 promoter sequence in 49 HCC patients. RNAseq data from 10 genotyped HCC samples were grouped according to their -77VNTR or -3SNP genotype to evaluate the impact of these polymorphisms on the differential expression on the HCC transcriptome. RESULTS: There is a fourfold higher impact of the -77VNTR on the HCC transcriptome compared to the -3SNP (q < 0.1, p < 0.001). The expression of the primary IFNAR1 transcript is not affected by these polymorphisms but a secondary, HCC-specific transcript is expressed only in homozygous -77VNTR ≤8/≤8(GT)n samples (p < 0.05). At the same time, patients carrying at least one -77VNTR >8(GT) allele, presented a strong upregulation of the fibronectin-1 (FN-1) gene, which has been associated with the development of HCC. Gene Ontology and pathway enrichment analysis of the differentially expressed genes revealed a strong disruption of the PI3K-AKT signaling pathway, which can be partially triggered by the extracellular matrix FN-1. CONCLUSION: The IFNAR-1 promoter polymorphisms are not involved in the expression levels of the main IFNAR-1 transcript. The -77VNTR has a regulatory role on the expression of a secondary, truncated, HCC-specific transcript, which in turn coincides with disruptions in cancer-associated pathways and in FN-1 expression modifications.
Colorectal cancer (CRC) is among the most common cancers. In fact, it is placed in the third place among the most diagnosed cancer in men, after lung and prostate cancer, and in the second one for the most diagnosed cancer in women, following breast cancer. Moreover, its high mortality rates classifies it among the leading causes of cancer‑related death worldwide. Thus, in order to help clinicians to optimize their practice, it is crucial to introduce more effective tools that will improve not only early diagnosis, but also prediction of the most likely progression of the disease and response to chemotherapy. In that way, they will be able to decrease both morbidity and mortality of their patients. In accordance with that, colon cancer research has described numerous biomarkers for diagnostic, prognostic and predictive purposes that either alone or as part of a panel would help improve patient's clinical management. This review aims to describe the most accepted biomarkers among those proposed for use in CRC divided based on the clinical specimen that is examined (tissue, faeces or blood) along with their restrictions. Lastly, new insight in CRC monitoring will be discussed presenting promising emerging biomarkers (telomerase activity, telomere length and micronuclei frequency).
Given globalization and other social phenomena, controlling the spread of infectious diseases has become an imperative public health priority. A plethora of interventions that in theory can mitigate the spread of pathogens have been proposed and applied. Evaluating the effectiveness of such interventions is costly and in many circumstances unrealistic. Most important, the community effect (i.e., the ability of the intervention to minimize the spread of the pathogen from people who received the intervention to other community members) can rarely be evaluated. Here we propose a study design that can build and evaluate evidence in support of the community effect of an intervention. The approach exploits molecular evolutionary dynamics of pathogens in order to track new infections as having arisen from either a control or an intervention group. It enables us to evaluate whether an intervention reduces the number and length of new transmission chains in comparison with a control condition, and thus lets us estimate the relative decrease in new infections in the community due to the intervention. We provide as an example one working scenario of a way the approach can be applied with a simulation study and associated power calculations.
Inspired by the work of Molino, we show that the integrability obstruction for transitive Lie algebroids can be made to vanish by adding extra dimensions. In particular, we prove that the Weinstein groupoid of a non-integrable transitive and abelian Lie algebroid is the quotient of a finite-dimensional Lie groupoid. Two constructions as such are given: First, explaining the counterexample to integrability given by Almeida and Molino, we see that it can be generalized to the construction of an “Almeida–Molino” integrable lift when the base manifold is simply connected. On the other hand, we notice that the classical de Rham isomorphism provides a universal integrable algebroid. Using it we construct a “de Rham” integrable lift for any given transitive Abelian Lie algebroid.
Muscle fascicle length and muscle fibre conduction velocity are thought to be important parameters for power performance. It might be expected that faster muscle fibre conduction velocities would compensate for longer fascicle lengths to increase the speed of action potential propagation along the elongated fibres. However, the relationship between muscle fascicle length and muscle fibre conduction velocity (MFCV) remains unknown. The aim of the present study was to explore the relationship between average vastus lateralis MFCV and average fascicle length. In seventeen moderately-trained healthy male physical education students (age 23.4 ± 3.1 years, body height 178 ± 5.5 cm, body mass 82.7 ± 6.9 kg, BMI 24.6 ± 1.5 kg∙m-2) resting MFCV was measured with intramuscular microelectrodes while muscle architecture was evaluated with ultrasonography. Fascicle length was highly correlated with total MFCV (r: 0.923, p = 0.000), maximum MFCV (r: 0.949, p = 0.000), and MFCV of the fastest (r: 0.709, p = 0.001), but not of the slowest fibres (r: 0.131, p = 0.616). No significant correlations were also found between vastus lateralis thickness or fascicle angle with any of MFCV parameters (r: 0.145 - 0.430; R2 < 0.130; p > 0.05). These data indicate that average MFCV is associated with average fascicle length in vastus lateralis muscle in different individuals. It seems that participants with longer fascicle lengths have also higher muscle fibre conduction velocities.
Accurate sexing methods are of great importance in forensic anthropology since sex assessment is among the principal tasks when examining human skeletal remains. The present study explores a novel approach in assessing the most accurate metric traits of the human cranium for sex estimation based on 80 ectocranial landmarks from 176 modern individuals of known age and sex from the Athens Collection. The purpose of the study is to identify those distance and angle measurements that can be most effectively used in sex assessment. Three-dimensional landmark coordinates were digitized with a Microscribe 3DX and analyzed in GNU Octave. An iterative linear discriminant analysis of all possible combinations of landmarks was performed for each unique set of the 3160 distances and 246,480 angles. Cross-validated correct classification as well as multivariate DFA on top performing variables reported 13 craniometric distances with over 85% classification accuracy, 7 angles over 78%, as well as certain multivariate combinations yielding over 95%. Linear regression of these variables with the centroid size was used to assess their relation to the size of the cranium. In contrast to the use of generalized procrustes analysis (GPA) and principal component analysis (PCA), which constitute the common analytical work flow for such data, our method, although computational intensive, produced easily applicable discriminant functions of high accuracy, while at the same time explored the maximum of cranial variability.
Ruess S, Avramidis KA, Fuchs M, Gantenbein G, Ioannidis Z, Illy S, Jin J, Kalaria PC, Kobarg T, Pagonakis IG, et al.KIT coaxial gyrotron development: From ITER toward DEMO. International Journal of Microwave and Wireless Technologies [Internet]. 2018;10:547-555. Website
Ruess S, Avramidis KA, Fuchs M, Gantenbein G, Ioannidis Z, Illy S, Jin J, Kalaria PC, Kobarg T, Pagonakis GI, et al.{KIT} coaxial gyrotron development: from {ITER} toward {DEMO}. International Journal of Microwave and Wireless Technologies [Internet]. 2018;10:547–555. Website
Intimement liée aux divers projets, créations et réformes relatives à l’organisation d’une formation initiale, l’évolution des programmes de formation culturelle des francisants grecs au XXe siècle doit être étudiée dans une double optique. Celle, tout d’abord, que proposent les voies originales qu’emprunta le processus de disciplinarisation des études françaises en Grèce. Cette approche est, par ailleurs, inséparable d’une autre, plus politique : fruits d’une collaboration franco-hellénique étroite autant qu’ambiguë, les programmes d’enseignement des structures projetées ou mises en place entre 1914 et 1976 constituent, d’une certaine manière, le reflet des fluctuations des relations diplomatiques et culturelles entre les deux pays.Intimately linked with the various projects, creations and reforms related to the organization of an initial training, the development of the cultural curricula of the Greek Teachers of French in the twentieth century must be studied in a dual perspective. Primarily the one that is proposed by the original ways that borrow the process of disciplinarization of French studies in Greece. This approach is, moreover, inseparable from another, more political: fruits of close as well as ambiguous French-Hellenic cooperation, the educational programs of the structures designed or created between 1914 and 1976 are, in some way, the reflection of the fluctuations of diplomatic and cultural relations between the two countries.
Mucinous adenocarcinoma associated with an anal fistula is a rare oncologic entity which may pose diagnostic and therapeutic challenges for Surgeons and Medical Oncologists. Few reported cases without definite therapeutic guidelines exist. It represents 2-3% of all gastrointestinal malignancies and arises from chronic anal fistulas, ischiorectal or perianal abscesses. We report a case of perianal mucinous adenocarcinoma in a 65-year-old male initially surgically treated multiple times for a recurrent fistula in ano of 5 years duration. He presented with an ischiorectal and a perianal fistula. Incisional biopsy from fistulotomy revealed mucinous adenocarcinoma. Contrast enhanced computed tomography scan and magnetic resonance imaging showed a localized perianal growth of a tumor which was further evaluated with colonoscopy. With no evidence of metastasis, we performed a laparoscopic abdominoperineal resection (APR). Two years follow-up after APR and without adjuvant chemotherapy there is not any evidence of recurrence or distant metastasis.
Although there is rich evidence for human occupation of Paros’ coastline, there is a dearth of data with regards to the evolution of the island's seaboard palaeoenvironments. In this paper, we use sedimentological and palaeontological proxies of late Holocene coastal deposits from lagoonal environment to reconstruct the evolution of coastal landscapes in Paroikia Bay (Paros Island, Greece). A semi-enclosed lagoon existed in the northeastern part of Paroikia from at least 2915–2551 BC, which was gradually infilled after around 780–436 BC. Although it was not possible to chronologically constrain the timing of the infill, it is most likely relatively young, indicating anthropogenic effects. A correlation of our chronostratigraphic data with archaeological remains and tidal notches in the study area suggests that the subsidence observed on Paros Island is linked to long-term subsidence in combination with vertical seismic displacements.
INTRODUCTION: Lung ischemia-reperfusion injury after thoracoabdominal aortic occlusion represents a major complication, which increases morbidity and mortality. In the present study we hypothesized that lazaroid U-74389G intravenous administration protects from lung ischemia-reperfusion injury through lipid peroxidation inhibition. MATERIALS AND METHODS: A total of 24 pigs were randomized in three groups. Group I (n=8) underwent sham operation, group II (n=8) underwent thoracoabdominal aortic occlusion for 45min and received placebo and group III (n=8) received 3 doses of lazaroid (3mg/kg) 60 and 30min before thoracoabdominal aortic occlusion and at 30min during thoracoabdominal aortic occlusion (duration 45min). Aortic occlusion was performed with aortic balloon-catheters under fluoroscopic guidance. All animals were sacrificed at the 7th postoperative day and lung specimens were harvested for molecular analysis. RESULTS: mRNA levels of leukotrienes LB4 (LTB4R2), LC4 (LTC4S) and nitric oxide synthase (NOS) isoforms including iNOS, nNOS and eNOS were determined with real-time RT-qPCR. Nitric oxide can either induce (iNOS) or inhibit (nNOS and eNOS) lipid peroxidation based on its specific isoform origin. Group III showed significantly reduced mRNA levels of LTB4R2 (-63.7%), LTC4S (-35.9%) and iNOS (-60.2%) when compared with group II (P < 0.05, for all). The mRNA levels of nNOS was significantly increased (+37.4%), while eNOS was slightly increased (+2.1%) in group III when compared with group II (P < 0.05 and P = 0.467 respectively). CONCLUSION: Lazaroid U-74389G may represent an effective pharmacologic intervention in reducing lung ischemia-reperfusion injury following thoracoabdominal aortic occlusion
The present study focuses on adult trainees’ reflection upon their personal course of action and development on completing the five-year long post graduate program: “Adult Education” at the Hellenic Open University. Reflecting back, students where asked to evaluate their experience. It seems that learning within the research context is positively experienced. The positive aspects are relevant to how participants in this study managed to communicate with others when they were asked to express their own assumptions and reflect feelings and thoughts in a context of critical thinking and open dialogue.
ABSTRACTWe exploit macroseismic observations and instrumental data aiming at explaining the effects of the 17th November 2015 Mw=6.5 earthquake, occurred beneath the southwestern peninsula of Lefkas Island (Ionian Sea) causing two casualties, major geo-environmental and slight-to-moderate structural effects. The spatial distribution of the structural damage of the local building stock is well correlated with the deformation pattern deduced from satellite geodesy, it appears though considerably low with respect to the ground deformation. Comparison with the previous strong earthquake on 14.8.2003 with Mw=6.2 occurred about 20 km to the north, shows that structural damage was significantly lower during the recent quake and also manifests good behaviour of the local buildings. This is partly explained by the characteristics of the ground motion and primarily explained by the unique concepts applied to the non-engineered buildings of Lefkas to resist ground motions.
n Volleyball a team’s performance in skills is connected to the game result and to the team’s success in a championship. In order to identify the determinant parameters for the success in male volleyball, performance data for all teams of 12 Greek Volleyball championships from 2005-06 until 2016-17 (n=143) was used. The effectiveness of fourteen (14) parameters from 5 basic volleyball skills: serve, attack after passing, attack after defence, block and reception was examined. The findings lead to the conclusion that the best predictors of a team’s success in final ranking are serve aces, passing errors, precise pass and attack after pas sing or after defence. The relevant discriminant function has classified correctly 77.6% of the teams in positions 1-4, 5-8 and 9-12. Furthermore, among teams in positions 1-2 and 3-4 (n=48) the variables attack win and attack error, after reception and de fence have significantly higher scores and are able to discriminate correctly 83,3% of the original cases.
BACKGROUND: Bladder cancer (BlCa) heterogeneity and the lack of personalised prognosis lead to patients' highly variable treatment outcomes. Here, we have analysed the utility of the GAS5 tumour-suppressor lncRNA in improving BlCa prognosis. METHODS: GAS5 was quantified in a screening cohort of 176 patients. Hedegaard et al. (2016) (n = 476) and TCGA provisional (n = 413) were used as validation cohorts. Survival analysis was performed using recurrence and progression for NMIBC, or death for MIBC. Internal validation was performed by bootstrap analysis, and decision curve analysis was used to evaluate the clinical benefit on disease prognosis. RESULTS: GAS5 levels were significantly downregulated in BlCa and associated with invasive high-grade tumours, and high EORTC-risk NMIBC patients. GAS5 loss was strongly and independently correlated with higher risk for NMIBC early relapse (HR = 2.680, p = 0.011) and progression (HR = 6.362, p = 0.035). Hedegaard et al. and TCGA validation cohorts' analysis clearly confirmed the association of GAS5 loss with NMIBC worse prognosis. Finally, multivariate models incorporating GAS5 with disease established markers resulted in higher clinical benefit for NMIBC prognosis. CONCLUSIONS: GAS5 loss is associated with adverse outcome of NMIBC and results in improved positive prediction of NMIBC patients at higher risk for short-term relapse and progression, supporting personalised prognosis and treatment decisions.
Cardiovascular disease (CVD) continues to be the leading cause of global morbidity and mortality. Heart failure remains a major contributor to this mortality. Despite major therapeutic advances over the past decades, a better understanding of molecular and cellular mechanisms of CVD as well as improved therapeutic strategies for the management or treatment of heart failure are increasingly needed. Loss of myocardium is a major driver of heart failure. An attractive approach that appears to provide promising results in reducing cardiac degeneration is stem cell therapy (SCT). In this review, we describe different types of stem cells, including embryonic and adult stem cells, and we provide a detailed discussion of the properties of induced pluripotent stem cells (iPSCs). We also present and critically discuss the key methods used for converting somatic cells to pluripotent cells and iPSCs to cardiomyocytes (CMs), along with their advantages and limitations. Integrating and non-integrating reprogramming methods as well as characterization of iPSCs and iPSC-derived CMs are discussed. Furthermore, we critically present various methods of differentiating iPSCs to CMs. The value of iPSC-CMs in regenerative medicine as well as myocardial disease modeling and cardiac regeneration are emphasized.
We analyzed the massive star population of the Virgo Cluster galaxy NGC 4535 using archival Hubble Space Telescope Wide Field Planetary Camera 2 images in filters F555W and F814W, equivalent to Johnson V and Kron-Cousins I. We performed high precision point spread function fitting photometry of 24353 sources including 3762 candidate blue supergiants, 841 candidate yellow supergiants, and 370 candidate red supergiants. We estimated the ratio of blue to red supergiants as a decreasing function of galactocentric radius. Using Modules for Experiments in Stellar Astrophysics (MESA) isochrones at solar metallicity, we defined the luminosity function and estimated the star formation history of the galaxy over the last 60 Myr. We conducted a variability search in the V and I filters using three variability indexes: the median absolute deviation, the interquartile range, and the inverse von-Neumann ratio. This analysis yielded 120 new variable candidates with absolute magnitudes ranging from MV = -4 to -11 mag. We used the MESA evolutionary tracks at solar metallicity to classify the variables based on their absolute magnitude and their position on the color-magnitude diagram. Among the new candidate variable sources are eight candidate variable red supergiants, three candidate variable yellow supergiants and one candidate luminous blue variable, which we suggest for follow-up observations. Full Table A.1 is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/618/A185
Mitophagy is an evolutionarily conserved cellular process to remove dysfunctional or superfluous mitochondria, thus fine-tuning mitochondrial number and preserving energy metabolism. In this Review, we survey recent advances towards elucidating the molecular mechanisms that mediate mitochondrial elimination and the signalling pathways that govern mitophagy. We consider the contributions of mitophagy in physiological and pathological contexts and discuss emerging findings, highlighting the potential value of mitophagy modulation in therapeutic intervention.
We report on the optical response of a nonreciprocal bianisotropic metamaterial, consisting of spherical, metal-coated magnetic nanoparticles embedded in an optically active medium, thus combining gyrotropy, plasmonic resonances, and chirality in a versatile design. The corresponding effective medium is deduced by an appropriate two-step generalized Maxwell-Garnett homogenization scheme. The associated photonic band structure and transmission spectra are obtained through a six-vector formulation of Maxwell equations, which provides an efficient framework for general bianisotropic structures going beyond existing approaches that involve cumbersome nonlinear eigenvalue problems. Our results, analyzed and discussed in the light of group theory, provide evidence that the proposed metamaterial exhibits some remarkable frequency-tunable properties, such as strong, plasmon-enhanced nonreciprocal polarization azimuth rotation and magnetochiral dichroism.
Right or subtotal colectomy either open or laparoscopic may be a challenging operation owing to technical difficulties. One of these, is to identify a safe and adequate dissection plane, ligating and dissecting lymph nodes around middle colic vessels. The purpose of this study was to depict a rare anatomic variation of middle colic vein (MCV) draining to splenic vein. We report the case of a 55-year-old male patient, who was subjected to a right hemicolectomy for an adenocarcinoma in the ascending colon. During dissecting the transverse mesocolon from the greater omentum, for complete mesocolic excision (CME), we encountered that the MCV drained in the splenic vein. With respect of this rare anatomic variability, CME was completed without hemorrhage. Our aim is to depict that deep knowledge of MCV anatomy and its variations is of paramount importance to achieve CME and to avoid dangerous or massive bleeding.
Clinical heterogeneity of bladder cancer prognosis requires the identification of bladder tumors' molecular profile to improve the prediction value of the established and clinically used markers. In this study, we have analyzed miR-221/222 cluster expression in bladder tumors and its clinical significance for patients' prognosis and disease outcome. The study included 387 tissue specimens. Following extraction, total RNA was polyadenylated at 3'-end and reversed transcribed. SYBR-Green based qPCR assays were performed for the quantification of miR-221/222 expression. Extensive statistical analysis was completed for the evaluation of miR-221/222 cluster's clinical significance. The expression of miR-221/222 is significantly downregulated in tumors compared to normal urothelium, while ROC curve and logistic regression analysis highlighted cluster's discriminatory ability. However, miR-222 levels were increased in muscle-invasive (T2-T4) compared to superficial tumors (TaT1), and in high compared to low-grade tumors. Kaplan-Meier survival curves and Cox regression analysis revealed the stronger risk of TaT1 patients overexpressing miR-222 for disease short-term relapse and progression following treatment. Moreover, multivariate Cox models highlighted the independent prognostic value of miR-222 overexpression for TaT1 patients' poor prognosis. Finally, the analysis of miR-222 expression improved significantly the positive prediction strength of the clinically used prognostic markers of tumor stage, grade, EORTC risk-stratification and recurrence at the first follow-up cystoscopy for TaT1 patients' outcome, and resulted to higher clinical net benefit following decision curve analysis. In conclusion, the expression of miR-221/222 cluster is deregulated in bladder tumors and miR-222 overexpression results to a superior positive prediction of TaT1 patients' short-term relapse and progression.
INTRODUCTION: The elucidation of tumor molecular hallmarks and the identification of novel molecular markers are of first translational priority in breast and ovarian cancer research, aiming to support personalized disease treatment and monitoring decisions. Recent high-throughput studies have revealed that ~ 80% of the genome is transcribed into RNAs without protein-coding potential, namely non-coding RNAs (ncRNAs), challenging the concept of 'junk DNA'. Undoubtedly, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) represent the best-studied family classes, emerging as the most powerful gene-expression regulators at epigenetic, transcriptional and post-transcriptional levels. Areas covered: Cancer research has highlighted the active implication of ncRNAs, most notably of miRNAs and lncRNAs, in almost every aspect of the cancer cells' biology as well as their deregulated expression in both breast and ovarian tumors. In the present manuscript we discuss the existing knowledge regarding the involvement of miRNAs and lncRNAs in the molecular background of breast and ovarian malignancies, to highlight their clinical utility in improving disease management. Expert commentary: miRNAs and lncRNAs represent central mediators of cancer cells' phenotype, and promising molecular markers and therapeutic targets to support precision medicine in breast and ovarian cancers.
The mixed sandwich U(III) complex {U[η8-C8H6(1,4-Si(iPr)3)2](Cp*)(THF)} reacts with the organic azides RN3 (R = SiMe3, 1-Ad, BMes2) to afford the corresponding, structurally characterised U(V) imido complexes {U[η8-C8H6(1,4-Si(iPr)3)2](Cp*)(NR)}. In the case of R = SiMe3, the reducing power of the U(III) complex leads to reductive coupling as a parallel minor reaction pathway, forming R-R and the U(IV) azide-bridged complex{[U]}2(μ-N3)2, along with the expected [U] = NR complex. All three [U] = NR complexes show a quasi-reversible one electron reduction between −1.6 and −1.75 V, and for R = SiMe3, chemical reduction using K/Hg affords the anionic U(IV) complex K+{U[η8-C8H6(1,4-Si(iPr)3)2](Cp*) = NSiMe3}-. The molecular structure of the latter shows an extended structure in the solid state in which the K counter cations are successively sandwiched between the Cp* ligand of one [U] anion and the COTtips2 ligand of the next.
Disorders of neuronal mispositioning during brain development are phenotypically heterogeneous and their genetic causes remain largely unknown. Here, we report biallelic variants in a Hippo signaling factor-MOB2-in a patient with one such disorder, periventricular nodular heterotopia (PH). Genetic and cellular analysis of both variants confirmed them to be loss-of-function with enhanced sensitivity to transcript degradation via nonsense mediated decay (NMD) or increased protein turnover via the proteasome. Knockdown of Mob2 within the developing mouse cortex demonstrated its role in neuronal positioning. Cilia positioning and number within migrating neurons was also impaired with comparable defects detected following a reduction in levels of an upstream modulator of Mob2 function, Dchs1, a previously identified locus associated with PH. Moreover, reduced Mob2 expression increased phosphorylation of Filamin A, an actin cross-linking protein frequently mutated in cases of this disorder. These results reveal a key role for Mob2 in correct neuronal positioning within the developing cortex and outline a new candidate locus for PH development.
Background: The Transmission Reduction Intervention Project (TRIP) is a network-based intervention that aims at decreasing human immunodeficiency virus type 1 (HIV-1) spread. We herein explore associations between transmission links as estimated by phylogenetic analyses, and social network-based ties among persons who inject drugs (PWID) recruited in TRIP. Methods: Phylogenetic trees were inferred from HIV-1 sequences of TRIP participants. Highly supported phylogenetic clusters (transmission clusters) were those fulfilling 3 different phylogenetic confidence criteria. Social network-based ties (injecting or sexual partners, same venue engagement) were determined based on personal interviews, recruitment links, and field observation. Results: TRIP recruited 356 individuals (90.2% PWID) including HIV-negative controls; recently HIV-infected seeds; long-term HIV-infected seeds; and their social network members. Of the 150 HIV-infected participants, 118 (78.7%) were phylogenetically analyzed. Phylogenetic analyses suggested the existence of 13 transmission clusters with 32 sequences. Seven of these clusters included 14 individuals (14/32 [43.8%]) who also had social ties with at least 1 member of their cluster. This proportion was significantly higher than what was expected by chance. Conclusions: Molecular methods can identify HIV-infected people socially linked with another person in about half of the phylogenetic clusters. This could help public health efforts to locate individuals in networks with high transmission rates.
BACKGROUND: The Transmission Reduction Intervention Project (TRIP) is a network-based intervention that aims at decreasing human immunodeficiency virus type 1 (HIV-1) spread. We herein explore associations between transmission links as estimated by phylogenetic analyses, and social network-based ties among persons who inject drugs (PWID) recruited in TRIP. METHODS: Phylogenetic trees were inferred from HIV-1 sequences of TRIP participants. Highly supported phylogenetic clusters (transmission clusters) were those fulfilling 3 different phylogenetic confidence criteria. Social network-based ties (injecting or sexual partners, same venue engagement) were determined based on personal interviews, recruitment links, and field observation. RESULTS: TRIP recruited 356 individuals (90.2% PWID) including HIV-negative controls; recently HIV-infected seeds; long-term HIV-infected seeds; and their social network members. Of the 150 HIV-infected participants, 118 (78.7%) were phylogenetically analyzed. Phylogenetic analyses suggested the existence of 13 transmission clusters with 32 sequences. Seven of these clusters included 14 individuals (14/32 [43.8%]) who also had social ties with at least 1 member of their cluster. This proportion was significantly higher than what was expected by chance. CONCLUSIONS: Molecular methods can identify HIV-infected people socially linked with another person in about half of the phylogenetic clusters. This could help public health efforts to locate individuals in networks with high transmission rates.
BACKGROUND: Current chemotherapy regimens for the treatment of colorectal cancer (CRC) include oxaliplatin, irinotecan, and fluorouracil along with leucovorin. Cytotoxicity involves the induction of programmed cell death. OBJECTIVE: The purpose of this study was to assess the molecular effects of doxorubicin (a 14-OH derivative of the natural product daunorubicin) and common chemotherapeutic drugs (used in the clinical practice to treat CRC) on the expression of the most prominent members of the BCL2 family, namely BCL2, BAX, BCLX, and MCL1. Moreover, we sought to define the role of BCL2L12, another member of the BCL2 family, the apoptotic role of which is ambiguous. METHODS: The MTT cell proliferation assay was used to determine the IC50 of each chemotherapeutic drug at 72 hours of treatment of Caco-2 and DLD-1 colorectal adenocarcinoma cell lines. Real-time PCR was used to quantify the antiapoptotic BCL2-alpha, BLCX-L, and MCL1-L transcripts, the proapoptotic BAX, BLCX-S, BLCX-ES, MCL1-S, and MCL1-ES transcripts, and BCL2L12 expression in relation to GAPDH mRNA levels. RESULTS: We constructed growth curves of Caco-2 and DLD-1 cells and determined the IC50 of each drug at 72 hours of treatment. Significant alterations in the expression levels of the studied BCL2 family genes and/or particular transcripts were observed. CONCLUSION: The intrinsic apoptotic pathway is activated during treatment of CRC cells with common chemotherapeutic drugs. Moreover, BCL2L12 mRNA expression increases progressively during treatment, similarly to the expression of other BCL2 family genes favoring apoptosis and/or particular proapoptotic transcripts, thus suggesting a proapoptotic role for BCL2L12 in chemotherapy-treated CRC cells.
Ukraine has one of the largest HIV epidemics in Europe, historically driven by people who inject drugs (PWID). The epidemic showed signs of stabilization in 2012, but the recent war in eastern Ukraine may be reigniting virus spread. We investigated the movement of HIV-infected people within Ukraine before and during the conflict. We analyzed HIV-1 subtype-Anucleotide sequences sampled during 2012-2015 from 427 patients of 24 regional AIDS centers and used phylogeographic analysis to reconstruct virus movement among different locations in Ukraine. We then tested for correlations between reported PWID behaviors and reconstructed patterns of virus spread. Our analyses suggest that Donetsk and Lugansk, two cities not controlled by the Ukrainian government in eastern Ukraine, were significant exporters of the virus to the rest of the country. Additional analyses showed that viral dissemination within the country changed after 2013. Spearman correlation analysis showed that incoming virus flow was correlated with the number of HIV-infected internally displaced people. Additionally, there was a correlation between more intensive virus movement and locations with a higher proportion of PWID practicing risky sexual behaviors. Our findings suggest that effective prevention responses should involve internally displaced people and people who frequently travel to war-affected regions. Scale-up of harm reduction services for PWID will be an important factor in preventing new local HIV outbreaks in Ukraine.
New diagnoses of HIV-1 infection among people who inject drugs (PWID) rocketed in Athens, Greece between 2011 and 2014 (HIV-1 outbreak). Our aim was to identify, during that period, potential cross-group transmissions between the within-Greece PWID and other risk or national groups using molecular methods. Sequences from 33 PWID were outside the PWID-outbreak networks in Greece (PWID-imported transmissions). Phylogenetic analyses on 28 of these sequences (subtypes A and B) showed that 11 subtype B infections originated from Greece, whereas 8 and 7 subtype A strains were from former Soviet Union countries (A(FSU)) and Greece, respectively. The putative source in half of the PWID-imported transmissions with Greek origin was an individual who acquired HIV via sexual contact. During four years of an HIV-1 outbreak among PWID in Athens, Greece, 33 individuals in this group (4.6% of all diagnoses with phylogenetic analyses) are likely to represent infections, sexually or injection-acquired, outside the within-Greece-PWID-outbreak networks. Combined molecular and traditional HIV surveillance to monitor introductions of new strains, and interventions that aim at reducing the rate of both injection and sexual risky practices are needed during drug injection-related HIV outbreaks.
New diagnoses of HIV-1 infection among people who inject drugs (PWID) rocketed in Athens, Greece between 2011 and 2014 (HIV-1 outbreak). Our aim was to identify, during that period, potential cross-group transmissions between the within-Greece PWID and other risk or national groups using molecular methods. Sequences from 33 PWID were outside the PWID-outbreak networks in Greece (PWID-imported transmissions). Phylogenetic analyses on 28 of these sequences (subtypes A and B) showed that 11 subtype B infections originated from Greece, whereas 8 and 7 subtype A strains were from former Soviet Union countries (AFSU) and Greece, respectively. The putative source in half of the PWID-imported transmissions with Greek origin was an individual who acquired HIV via sexual contact. During four years of an HIV-1 outbreak among PWID in Athens, Greece, 33 individuals in this group (4.6% of all diagnoses with phylogenetic analyses) are likely to represent infections, sexually or injection-acquired, outside the within-Greece-PWID-outbreak networks. Combined molecular and traditional HIV surveillance to monitor introductions of new strains, and interventions that aim at reducing the rate of both injection and sexual risky practices are needed during drug injection-related HIV outbreaks.
Proteasome is central to proteostasis network functionality and its overactivation represents a hallmark of advanced tumors; thus, its selective inhibition provides a strategy for the development of novel antitumor therapies. In support, proteasome inhibitors, e.g. Bortezomib or Carfilzomib have demonstrated clinical efficacy against hematological cancers. Herein, we studied proteasome regulation in peripheral blood mononuclear cells and erythrocytes isolated from healthy donors or from Multiple Myeloma patients treated with Bortezomib or Carfilzomib. In healthy donors we found that peripheral blood mononuclear cells express higher, as compared to erythrocytes, basal proteasome activities, as well as that proteasome activities decline during aging. Studies in cells isolated from Multiple Myeloma patients treated with proteasome inhibitors revealed that in most (but, interestingly enough, not all) patients, proteasome activities decline in both cell types during therapy. In peripheral blood mononuclear cells, most proteostatic genes expression patterns showed a positive correlation during therapy indicating that proteostasis network modules likely respond to proteasome inhibition as a functional unit. Finally, the expression levels of antioxidant, chaperone and aggresomes removal/autophagy genes were found to inversely associate with patients' survival. Our studies will support a more personalized therapeutic approach in hematological malignancies treated with proteasome inhibitors.
Detection of the IceCube-170922A neutrino coincident with the flaring blazar TXS 0506+056, the first and only ∼3σ high-energy neutrino source association to date, offers a potential breakthrough in our understanding of high-energy cosmic particles and blazar physics. We present a comprehensive analysis of TXS 0506+056 during its flaring state, using newly collected Swift, NuSTAR, and X-shooter data with Fermi observations and numerical models to constrain the blazar’s particle acceleration processes and multimessenger (electromagnetic (EM) and high-energy neutrino) emissions. Accounting properly for EM cascades in the emission region, we find a physically consistent picture only within a hybrid leptonic scenario, with γ-rays produced by external inverse-Compton processes and high-energy neutrinos via a radiatively subdominant hadronic component. We derive robust constraints on the blazar’s neutrino and cosmic-ray emissions and demonstrate that, because of cascade effects, the 0.1-100 keV emissions of TXS 0506+056 serve as a better probe of its hadronic acceleration and high-energy neutrino production processes than its GeV-TeV emissions. If the IceCube neutrino association holds, physical conditions in the TXS 0506+056 jet must be close to optimal for high-energy neutrino production, and are not favorable for ultrahigh-energy cosmic-ray acceleration. Alternatively, the challenges we identify in generating a significant rate of IceCube neutrino detections from TXS 0506+056 may disfavor single-zone models, in which γ-rays and high-energy neutrinos are produced in a single emission region. In concert with continued operations of the high-energy neutrino observatories, we advocate regular X-ray monitoring of TXS 0506+056 and other blazars in order to test single-zone blazar emission models, clarify the nature and extent of their hadronic acceleration processes, and carry out the most sensitive possible search for additional multimessenger sources.
Detection of the IceCube-170922A neutrino coincident with the flaring blazar TXS 0506+056, the first and only ∼3σ high-energy neutrino source association to date, offers a potential breakthrough in our understanding of high-energy cosmic particles and blazar physics. We present a comprehensive analysis of TXS 0506+056 during its flaring state, using newly collected Swift, NuSTAR, and X-shooter data with Fermi observations and numerical models to constrain the blazar’s particle acceleration processes and multimessenger (electromagnetic (EM) and high-energy neutrino) emissions. Accounting properly for EM cascades in the emission region, we find a physically consistent picture only within a hybrid leptonic scenario, with γ-rays produced by external inverse-Compton processes and high-energy neutrinos via a radiatively subdominant hadronic component. We derive robust constraints on the blazar’s neutrino and cosmic-ray emissions and demonstrate that, because of cascade effects, the 0.1-100 keV emissions of TXS 0506+056 serve as a better probe of its hadronic acceleration and high-energy neutrino production processes than its GeV-TeV emissions. If the IceCube neutrino association holds, physical conditions in the TXS 0506+056 jet must be close to optimal for high-energy neutrino production, and are not favorable for ultrahigh-energy cosmic-ray acceleration. Alternatively, the challenges we identify in generating a significant rate of IceCube neutrino detections from TXS 0506+056 may disfavor single-zone models, in which γ-rays and high-energy neutrinos are produced in a single emission region. In concert with continued operations of the high-energy neutrino observatories, we advocate regular X-ray monitoring of TXS 0506+056 and other blazars in order to test single-zone blazar emission models, clarify the nature and extent of their hadronic acceleration processes, and carry out the most sensitive possible search for additional multimessenger sources.
INTRODUCTION: The purpose of this study was to examine the effects of a short-term fast eccentric and ballistic complex training program on muscle power, rate of force development (RFD), muscle fiber composition, and cross-sectional area (CSA).
METHODS: Sixteen male physical education students were randomly assigned to either a training group (TG, n = 8) or a control group (n = 8). The TG followed a 6-wk low volume training program, including fast eccentric squat training with an individually optimized load of 74% ± 7% of maximal half-squat strength (1RM) twice per week and a ballistic training session with loaded (30% 1RM) and unloaded jump squats, once per week, all combined with unloaded plyometric jumps.
RESULTS: Half squat 1RM was increased in the TG from 1.87 ± 0.28 to 2.14 ± 0.31 kg per kilogram body mass (14.4% ± 9.3%, P = 0.01). The percentage of types I, IIA, and IIX fibers were similar in the two groups at pretesting and did not change after the intervention period (P = 0.53-0.89). Muscle fiber CSA increased in all fiber types by 8.3% to 11.6% (P = 0.02 to 0.001) in TG only. Countermovement jump height and peak power measured at five different external loads (0%-65% of 1RM) only increased in the TG by approximately 20% to 36% (P < 0.01) and approximately 16% to 22% (P < 0.01), respectively. Peak ground reaction force during jump squats remained unchanged in both groups, whereas RFD increased in the TG only (40%-107%, P = 0.001).
CONCLUSIONS: A combination of low-volume fast eccentric and ballistic jump squat training with plyometric jumps in a strength-power potentiation complex format, induced substantial increases in peak leg muscle power, RFD, and maximal strength, accompanied by gains in CSA of all muscle fiber types, without a reduction in fast twitch fiber composition.
Recently, four different operative techniques, referring to the primary anterior cruciate ligament (ACL) repair, were described. These are the dynamic intraligamentary stabilization (DIS) with Ligamys™, the Bridge-enhanced repair (BEAR), the use of internal brace, and the refixation with suture anchors. The purpose of this study was to assess the already-published, clinical, and pre-clinical results of those techniques. A literature review was conducted and implemented by three independent researchers. Inclusion criteria were clinical or cadaveric or animal studies about patients suffering from ACL rupture, who were treated with one of those four different arthroscopic techniques of primary ACL repair. There were 10 clinical trials dealing with the different techniques of primary ACL repair and 12 cadaveric or animal studies. The majority of the published clinical trials investigated the dynamic intraligamentary stabilization (DIS), while only four studies referred to the three other surgical techniques. Most of the clinical trials suggested that primary ACL repair should be done during the first 14-21 days after a proximal ACL rupture and not later. Further clinical evidence is needed for the techniques of bridge-enhanced ACL repair, internal brace, and suture anchors ACL refixation in order to support the animal and cadaveric biomechanical studies. Till now, the existing clinical trials were not enough to establish the use of those techniques in the ACL-ruptured patients. On the contrary, the Dynamic intraligamentary stabilization with Ligamys™ device demonstrated very promising results in different types of clinical studies.
BACKGROUND: TRIP (Transmission Reduction Intervention Project) was a network-based, contact tracing approach to locate and link to care, mostly people who inject drugs (PWID) with recent HIV infection. OBJECTIVE: We investigated whether sequences from HIV-infected participants with high viral load cluster together more frequently than what is expected by chance. METHODS: Paired end reads were generated for 104 samples using Illumina MiSeq next-generation sequencing. RESULTS: 63 sequences belonged to previously identified local transmission networks of PWID (LTNs) of an HIV outbreak in Athens, Greece. For two HIV-RNA cut-offs (105 and 106 IU/mL), HIV transmissions were more likely between PWID with similar levels of HIV-RNA (p<0.001). 10 of the 14 sequences (71.4%) from PWID with HIV-RNA >106 IU/mL were clustered in 5 pairs. For 4 of these clusters (80%), there was in each one of them at least one sequence from a recently HIVinfected PWID. CONCLUSION: We showed that transmissions are more likely among PWID with high viremia.
PURPOSE: This paper presents an overview of different kinds of risk and social network methods and the kinds of research questions each can address. RECENT FINDINGS: It also reviews what network research has discovered about how network characteristics are associated with HIV and other infections, risk behaviors, preventive behaviors, and care, and discusses some ways in which network-based public health interventions have been conducted. Based on this, risk and social network research and interventions seem both feasible and valuable for addressing the many public health and social problems raised by the widespread use of opioids in the US South.
Background: The thyroid gland has a special relationship with oxidative stress. While generation of oxidative substances is part of normal iodide metabolism during thyroid hormone synthesis, the gland must also defend itself against excessive oxidation in order to maintain normal function. Antioxidant and detoxification enzymes aid thyroid cells to maintain homeostasis by ameliorating oxidative insults, including during exposure to excess iodide, but the factors that coordinate their expression with the cellular redox status are not known. The antioxidant response system comprising the ubiquitously expressed NFE2-related transcription factor 2 (Nrf2) and its redox-sensitive cytoplasmic inhibitor Kelch-like ECH-associated protein 1 (Keap1) defends tissues against oxidative stress, thereby protecting against pathologies that relate to DNA, protein, and/or lipid oxidative damage. Thus, it was hypothesized that Nrf2 should also have important roles in maintaining thyroid homeostasis. Methods: Ubiquitous and thyroid-specific male C57BL6J Nrf2 knockout (Nrf2-KO) mice were studied. Plasma and thyroids were harvested for evaluation of thyroid function tests by radioimmunoassays and of gene and protein expression by real-time polymerase chain reaction and immunoblotting, respectively. Nrf2-KO and Keap1-KO clones of the PCCL3 rat thyroid follicular cell line were generated using CRISPR/Cas9 technology and were used for gene and protein expression studies. Software-predicted Nrf2 binding sites on the thyroglobulin enhancer were validated by site-directed in vitro mutagenesis and chromatin immunoprecipitation. Results: The study shows that Nrf2 mediates antioxidant transcriptional responses in thyroid cells and protects the thyroid from oxidation induced by iodide overload. Surprisingly, it was also found that Nrf2 has a dramatic impact on both the basal abundance and the thyrotropin-inducible intrathyroidal abundance of thyroglobulin (Tg), the precursor protein of thyroid hormones. This effect is mediated by cell-autonomous regulation of Tg gene expression by Nrf2 via its direct binding to two evolutionarily conserved antioxidant response elements in an upstream enhancer. Yet, despite upregulating Tg levels, Nrf2 limits Tg iodination both under basal conditions and in response to excess iodide. Conclusions: Nrf2 exerts pleiotropic roles in the thyroid gland to couple cell stress defense mechanisms to iodide metabolism and the thyroid hormone synthesis machinery, both under basal conditions and in response to excess iodide.
NGC 300 ULX1 is a newly identified ultra-luminous X-ray pulsar. The system is associated with the supernova impostor SN 2010da that was later classified as a possible supergiant Be X-ray binary. In this work we report on the spin period evolution of the neutron star based on all the currently available X-ray observations of the system. We argue that the X-ray luminosity of the system has remained almost constant since 2010, at a level above ten times the Eddington limit. Moreover, we find evidence that the spin period of the neutron star evolved from ∼126 s down to ∼18 s within a period of about 4 years. We explain this unprecedented spin evolution in terms of the standard accretion torque theory. An intriguing consequence for NGC 300 ULX1 is that a neutron star spin reversal should have occurred a few years after the SN 2010da event.
NICER observed the new transient Swift J005139.2-721704 located in the Small Magellanic Cloud (SMC), and discovered on 2018 Nov. 9 (ATel #12209). The source position identified using Swift XRT as RA=00:51:39.2 and DEC=-72:17:03.6 (with an uncertainty of 1.4 & Prime;, ATel #12209).
Context. High-resolution radio imaging of active galactic nuclei (AGN) has revealed that the jets of some sources present superluminal knots and transverse stratification. Recent observational projects, such as ALMA and γ-ray telescopes, such as HESS and HESS2 have provided new observational constraints on the central regions of rotating black holes in AGN, suggesting that there is an inner- or spine-jet surrounded by a disk wind. This relativistic spine-jet is likely to be composed of electron-positron pairs extracting energy from the black hole and will be explored by the future γ-ray telescope CTA. Aims: In this article we present an extension to and generalization of relativistic jets in Kerr metric of the Newtonian meridional self-similar mechanism. We aim at modeling the inner spine-jet of AGN as a relativistic light outflow emerging from a spherical corona surrounding a Kerr black hole and its inner accretion disk. Methods: The model is built by expanding the metric and the forces with colatitude to first order in the magnetic flux function. As a result of the expansion, all colatitudinal variations of the physical quantities are quantified by a unique parameter. Unlike previous models, effects of the light cylinder are not neglected. Results: Solutions with high Lorentz factors are obtained and provide spine-jet models up to the polar axis. As in previous publications, we calculate the magnetic collimation efficiency parameter, which measures the variation of the available energy across the field lines. This collimation efficiency is an integral part of the model, generalizing the classical magnetic rotator efficiency criterion to Kerr metric. We study the variation of the magnetic efficiency and acceleration with the spin of the black hole and show their high sensitivity to this integral. Conclusions: These new solutions model collimated or radial, relativistic or ultra-relativistic outflows in AGN or γ-ray bursts. In particular, we discuss the relevance of our solutions to modeling the M 87 spine-jet. We study the efficiency of the central black hole spin to collimate a spine-jet and show that the jet power is of the same order as that determined by numerical simulations.
Aging is a complex biological process affecting almost all living organisms. Although its detrimental effects on animals' physiology have been extensively documented, several aspects of the biology of aging are insufficiently understood. Mitochondria, the central energy producers of the cell, play vital roles in a wide range of cellular processes, including regulation of bioenergetics, calcium signaling, metabolic responses, and cell death, among others. Thus, proper mitochondrial function is a prerequisite for the maintenance of cellular and organismal homeostasis. Several mitochondrial quality control mechanisms have evolved to allow adaptation to different metabolic conditions, thereby preserving cellular homeostasis and survival. A tight coordination between mitochondrial biogenesis and mitochondrial selective autophagy, known as mitophagy, is a common characteristic of healthy biological systems. The balanced interplay between these two opposing cellular processes dictates stress resistance, healthspan, and lifespan extension. Mitochondrial biogenesis and mitophagy efficiency decline with age, leading to progressive accumulation of damaged and/or unwanted mitochondria, deterioration of cellular function, and ultimately death. Several regulatory factors that contribute to energy homeostasis have been implicated in the development and progression of many pathological conditions, such as neurodegenerative, metabolic, and cardiovascular disorders, among others. Therefore, mitophagy modulation may serve as a novel potential therapeutic approach to tackle age-associated pathologies. Here, we review the molecular signaling pathways that regulate and coordinate mitophagy with mitochondrial biogenesis, highlighting critical factors that hold promise for the development of pharmacological interventions toward enhancing human health and quality of life throughout aging.
Superparamagnetic iron oxide nanoparticles with well-integrated multimodality imaging properties have generated increasing research interest in the past decade, especially when it comes to the targeted imaging of tumors. Bevacizumab (BCZM) on the other hand is a well-known and widely applied monoclonal antibody recognizing VEGF-A, which is overexpressed in angiogenesis. The aim of this proof-of-concept study was to develop a dual-modality nanoplatform for in vivo targeted single photon computed emission tomography (SPECT) and magnetic resonance imaging (MRI) of tumor vascularization. Iron oxide nanoparticles (IONPs) have been coated with dimercaptosuccinic acid (DMSA), for consequent functionalization with the monoclonal antibody BCZM radiolabeled with Tc-99m, via well-developed surface engineering. The IONPs were characterized based on their size distribution, hydrodynamic diameter and magnetic properties. In vitro cytotoxicity studies showed that our nanoconstruct does not cause toxic effects in normal and cancer cells. Fe3O4-DMSA-SMCC-BCZM-Tc-99m were successfully prepared at high radiochemical purity (> 92%) and their stability in human serum and in PBS were demonstrated. In vitro cell binding studies showed the ability of the Fe3O4-DMSA-SMCC-BCZM-Tc-99m to bind to the VEGF-165 isoform overexpressed on M-165 tumor cells. The ex vivo biodistribution studies in M165 tumor-bearing SCID mice showed high uptake in liver, spleen, kidney and lungs. The Fe3O4-DMSA-SMCC-BCZM-Tc-99m demonstrated quick tumor accumulation starting at 8.9 +/- 1.88% ID/g at 2 h p.i., slightly increasing at 4 h p.i. (16.21 +/- 2.56% ID/g) and then decreasing at 24 h p.i. (6.01 +/- 1.69% ID/g). The tumor-to-blood ratio reached a maximum at 24 h p.i. (similar to 7), which is also the case for the tumor-to- muscle ratio (similar to 18). Initial pilot imaging studies on an experimental gamma-camera and a clinical MR camera prove our hypothesis and demonstrate the potential of Fe3O4-DMSA-SMCC-BCZM-Tc-99m for targeted dual-modality imaging. Our findings indicate that Fe3O4-DMSA-SMCC-BCZM-Tc-99m IONPs could serve as an important diagnostic tool for biomedical imaging as well as a promising candidate for future theranostic applications in cancer.
The hippocampus and prefrontal cortex (PFC) are connected in a reciprocal manner: whereas the hippocampus projects directly to the PFC, a polysynaptic pathway that passes through the nucleus reuniens (RE) of the thalamus relays inputs from the PFC to the hippocampus. The present study demonstrates that lesioning and/or inactivation of the RE reduces coherence in the PFC-hippocampal pathway, provokes an antidepressant-like behavioral response in the forced swim test and prevents, but does not ameliorate, anhedonia in the chronic mild stress (CMS) model of depression. Additionally, RE lesioning before CMS abrogates the well-known neuromorphological and endocrine correlates of CMS. In summary, this work highlights the importance of the reciprocal connectivity between the hippocampus and PFC in the establishment of stress-induced brain pathology and suggests a role for the RE in promoting resilience to depressive illness.
The hippocampus and prefrontal cortex (PFC) are connected in a reciprocal manner: whereas the hippocampus projects directly to the PFC, a polysynaptic pathway that passes through the nucleus reuniens (RE) of the thalamus relays inputs from the PFC to the hippocampus. The present study demonstrates that lesioning and/or inactivation of the RE reduces coherence in the PFC-hippocampal pathway, provokes an antidepressant-like behavioral response in the forced swim test and prevents, but does not ameliorate, anhedonia in the chronic mild stress (CMS) model of depression. Additionally, RE lesioning before CMS abrogates the well-known neuromorphological and endocrine correlates of CMS. In summary, this work highlights the importance of the reciprocal connectivity between the hippocampus and PFC in the establishment of stress-induced brain pathology and suggests a role for the RE in promoting resilience to depressive illness.
Continuously rising trends in obesity-related malignancies render this disease spectrum a public health priority. Worldwide, the burden of cancer attributable to obesity, expressed as population attributable fraction, is 11.9% in men and 13.1% in women. There is convincing evidence that excess body weight is associated with an increased risk for cancer of at least 13 anatomic sites, including endometrial, esophageal, renal and pancreatic adenocarcinomas; hepatocellular carcinoma; gastric cardia cancer; meningioma; multiple myeloma; colorectal, postmenopausal breast, ovarian, gallbladder and thyroid cancers. We first synopsize current epidemiologic evidence; the obesity paradox in cancer risk and mortality; the role of weight gain and weight loss in the modulation of cancer risk; reliable somatometric indicators for obesity and cancer research; and gender differences in obesity related cancers. We critically summarize emerging biological mechanisms linking obesity to cancer encompassing insulin resistance and abnormalities of the IGF-I system and signaling; sex hormones biosynthesis and pathway; subclinical chronic low-grade inflammation and oxidative stress; alterations in adipokine pathophysiology; factors deriving from ectopic fat deposition; microenvironment and cellular perturbations including vascular perturbations, epithelial-mesenchymal transition, endoplasmic reticulum stress and migrating adipose progenitor cells; disruption of circadian rhythms; dietary nutrients; factors with potential significance such as the altered intestinal microbiome; and mechanic factors in obesity and cancer. Future perspectives regarding prevention, diagnosis and therapeutics are discussed. The aim of this review is to investigate how the interplay of these main potential mechanisms and risk factors, exerts their effects on target tissues provoking them to acquire a cancerous phenotype.
The X-ray source 1RXS J051439.2-021615 (RA 05h14m39.20s, Dec -02d16m15.00, J2000.0) showed an optical V-band flare, during the night of 25/26 January 2018 (JD=2458114).
The perennial geophyte sea daffodil, sea lily or sand lily (Pancratium maritimum L.) is a flowering species during the dry summer, widely distributed along Mediterranean seashores and grown in a wild stage. Populations of sea daffodil are exposed to sea breeze, salt spray, water shortage, strong solar radiation, elevated temperatures, substrate instability and moving sand. Also, it is expected that excessive tourism and human-induced activities will constrain the development of populations of P. maritimum, which have resulted from a long-term evolutionary process. P. maritimum exhibits large white flowers of a great aesthetic value during dry and hot summer weather conditions, when simultaneously flowering plant taxa are scarce. The buds remain protected below the soil surface on the underground perennial organ and the growth period alternates with a period of dormancy. The above-ground organs and tissues are exposed to harsh, ambient conditions and the large inflorescences of remarkable beauty and fragrance carry particular ornamental worth and thus economic value.
In Volleyball, complex 1 consists of pass-set-attack skills in this specified order. This sequence is a stable pattern to win a point. Furthermore, it is important for teams' success. Taking into account that this pattern is a first-order Markov chain, the creation of a probability transition matrix is feasible. Assuming multinomial likelihood with a Dirichlet prior on the transition probabilities a Markovian transition matrix can be constructed, and the calculation of conditional success probabilities is, thus, achievable. Data from the performance analysis of the winning team from recent world championships in three age categories (U19, U21, Men) of male Volleyball is used. Evaluation of the pass through a six-level ordinal scale is possible after the validation of the entire scale. The findings lead to redefining target pass area and to shrinking the evaluation scale at least for the teams under study. Moreover, pass accuracy is necessary because it must give at least two options for attack, but not sufficient condition for the success of attack in all age categories for male Volleyball. In U19 age category, there is a lack of stabilization in the complex 1 sequence after pass against jump spin serve.
A unique and often overlooked property of a source loaded with relativistic protons is that it can become supercritical, i.e. it can undergo an abrupt transition from a radiatively inefficient to a radiatively efficient state once its proton energy density exceeds a certain threshold. In this paper, we investigate the temporal variability of hadronic systems in this hardly explored regime. We show that there exists a range of proton densities that prevent the system from reaching a steady state, but drive it instead in a quasi-periodic mode. The escaping radiation then exhibits limit cycles, even if all physical parameters are held constant in time. We extend our analysis to cases where the proton injection rate varies with time and explore the variability patterns of escaping radiation as the system moves in and out from the supercritical regime. We examine the relevance of our results to the variability of the prompt gamma-ray burst emission and show that, at least on a phenomenological level, some interesting analogies exist.
A unique and often overlooked property of a source loaded with relativistic protons is that it can become supercritical, i.e. it can undergo an abrupt transition from a radiatively inefficient to a radiatively efficient state once its proton energy density exceeds a certain threshold. In this paper, we investigate the temporal variability of hadronic systems in this hardly explored regime. We show that there exists a range of proton densities that prevent the system from reaching a steady state, but drive it instead in a quasi-periodic mode. The escaping radiation then exhibits limit cycles, even if all physical parameters are held constant in time. We extend our analysis to cases where the proton injection rate varies with time and explore the variability patterns of escaping radiation as the system moves in and out from the supercritical regime. We examine the relevance of our results to the variability of the prompt gamma-ray burst emission and show that, at least on a phenomenological level, some interesting analogies exist.
Christopher Marlowe's The Massacre at Paris, a play which probably dates from 1592 but has reached posterity in a mangled form, enacts the incorporation of religious and state politics in the theatre. Through a sequence of short scenes characterized by senseless brutality and black humor, Marlowe revisits one of the darkest episodes of French history, the Saint Bartholomew‘s Day Massacre, which took place on the 24th and 25thAugust 1572. Dramatizing the slaughter of thousands of Protestants by Catholics, the play not only reflects on the significance of massacre as a political term for an increasingly absolutist Renaissance Europe but also translates the violence of massacre into aesthetic form. Itself alien within the body of Marlowe’s dramatic works, The Massacre at Paris has rarely been performed after its Elizabethan successful performances at the Rose; this is not surprising given the state of the extant text and its dismissal by many critics as crude anti-Catholic propaganda. Yet, the Massacre's corrupt and incomplete form, political ambiguities and emphasis on theatrical violence have inspired two contemporary artists, the French director Guillaume Delaveau and the Austrian composer Wolfgang Mitterer, to rethink and revive it. Both Delaveau's Massacre à Paris, first performed at Toulouse in 2007 and Mitterer's experimental opera Massacre, composed in 2003 and performed in 2008 and 2010 in France, refer to recent wars and atrocities and rejoice in the irony of the play. This paper seeks to investigate the play's ability to convey political thought and provoke contemporary audiences by reading it together with Delaveau and Mitterer's adaptations.The challenge of reworking the Massacre for our age involves the question of the theatre's potential to expose the audience to the horror of history.
Maternal affective disorders are frequently treated with selective serotonin reuptake inhibitor medications (SSRIs); with up to 10% of women being prescribed these medications during pregnancy. Infant development depends on the early serotonergic environment, which is altered by perinatal SSRIs, raising concern about how these medications affect neural outcomes. While clinical and preclinical research suggests an impact of SSRIs on the developing brain, more research is needed to determine the effects on neuroplasticity, the serotonergic system, and the hypothalamic-pituitary-adrenal axis in neural regions mediating behavior. The current work investigated the effects of the SSRI, fluoxetine, on the serotonergic system in the prefrontal cortex (PFC) during pre-adolescence, and changes to synaptic markers and glucocorticoid receptor density in the cingulate cortex (medial PFC) of pre-adolescent and adult Sprague-Dawley male and female rats. To model aspects of Perinatal Depression and maternal anxiety, pre-gestational maternal stress was used resulting in male and female offspring from 4 groups: 1) control, 2) perinatal fluoxetine exposed, 3) pre-gestational maternal stress exposed, and 4) pre-gestational maternal stress + fluoxetine. Perinatal fluoxetine prevented the effects of maternal stress on 5-HT levels and 5-HT turnover ratio in the PFC of pre-adolescent offspring, particularly in females. However, pre-gestational stress reduced synaptophysin and PSD-95 densities in the cingulate cortex, effects that were more pronounced in males. Interestingly, perinatal fluoxetine exposure reduced GR density in adult males in this same brain area. Together, results show differential effects of perinatal SSRIs and pre-gestational maternal stress on neurodevelopment in the PFC of males and females.
Maternal affective disorders are frequently treated with selective serotonin reuptake inhibitor medications (SSRIs); with up to 10% of women being prescribed these medications during pregnancy. Infant development depends on the early serotonergic environment, which is altered by perinatal SSRIs, raising concern about how these medications affect neural outcomes. While clinical and preclinical research suggests an impact of SSRIs on the developing brain, more research is needed to determine the effects on neuroplasticity, the serotonergic system, and the hypothalamic-pituitary-adrenal axis in neural regions mediating behavior. The current work investigated the effects of the SSRI, fluoxetine, on the serotonergic system in the prefrontal cortex (PFC) during pre-adolescence, and changes to synaptic markers and glucocorticoid receptor density in the cingulate cortex (medial PFC) of pre-adolescent and adult Sprague-Dawley male and female rats. To model aspects of Perinatal Depression and maternal anxiety, pre-gestational maternal stress was used resulting in male and female offspring from 4 groups: 1) control, 2) perinatal fluoxetine exposed, 3) pre-gestational maternal stress exposed, and 4) pre-gestational maternal stress + fluoxetine. Perinatal fluoxetine prevented the effects of maternal stress on 5-HT levels and 5-HT turnover ratio in the PFC of pre-adolescent offspring, particularly in females. However, pre-gestational stress reduced synaptophysin and PSD-95 densities in the cingulate cortex, effects that were more pronounced in males. Interestingly, perinatal fluoxetine exposure reduced GR density in adult males in this same brain area. Together, results show differential effects of perinatal SSRIs and pre-gestational maternal stress on neurodevelopment in the PFC of males and females.
We study the energy structure and the transfer of an extra electron or hole along periodic polymers made of N monomers, with a repetition unit made of P monomers, using a tight-binding wire model, where a site is a monomer (e.g., in DNA, a base pair), for P even, and deal with two categories of such polymers: made of the same monomer (GC…, GGCC…, etc.) and made of different monomers (GA…, GGAA…, etc.). We calculate the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) eigenspectra, density of states, and HOMO-LUMO gap and find some limiting properties these categories possess, as P increases. We further examine the properties of the mean over time probability to find the carrier at each monomer. We introduce the weighted mean frequency of each monomer and the total weighted mean frequency of the whole polymer, as a measure of the overall transfer frequency content. We study the pure mean transfer rates. These rates can be increased by many orders of magnitude with appropriate sequence choice. Generally, homopolymers display the most efficient charge transfer. Finally, we compare the pure mean transfer rates with experimental transfer rates obtained by time-resolved spectroscopy.
BACKGROUND: Firefighters participate in activities with intense physical and psychological stress and are constantly at risk to develop various psychopathological reactions. AIMS: To investigate psychological reactions in firefighters one month after devastating wildfires in Greece, during August 2007, which lead to the devastation of large areas and the death of 43 people among whom three were firefighters. METHODS: One month after the wildfires, a joint task force of mental health clinicians was organized in order to provide psychological support and to investigate the psychological consequences of wildfires to firefighters. One hundred and two firefighters, living within the fire-devastated area, who were on duty for the whole period of wildfires were interviewed and assessed with the use of several questionnaires and inventories. RESULTS: Post-traumatic stress disorder (PTSD) was detected in 18.6% of firefighters. Multiple logistic regression found that existence of fear of dying during firefighting, insomnia and increased scores in neuroticism, as well as in depression subscale of the SCL-90, were significantly associated with greater likelihood for having PTSD. Additionally those firefighters who worked permanently had 70% lower probability of having PTSD vs. those seasonally employed. CONCLUSIONS: Insomnia, depressive symptoms, as well as personality characteristics as neuroticism and the perception of fear of imminent death during firefighting operations may precipitate the development of PTSD in firefighters. Within this context, mental health clinicians should be aware that the early detection of these predisposing factors may facilitate the prevention and mitigation of PTSD in firefighters particularly those who are seasonally employed.
Dry powder inhalers containing the budesonide/formoterol combination have currently a well-established position among other inhaled products. Even though their efficacy mainly depends on the local concentrations of the drug they deliver within the lungs, their safety profile is directly related to their total systemic exposure. The aim of the present investigation was to explore the absorption and disposition kinetics of the budesonide/formoterol combination delivered via two different dry powder inhalers in asthma patients. Plasma concentration time data were obtained from a single-dose, crossover bioequivalence study in asthma patients. Non compartmental and population compartmental approaches were applied to the available datasets. The non compartmental analysis allowed for an initial characterization of the primary pharmacokinetic (PK) parameters of the two inhaled drugs and subsequently the bioequivalence assessment of the two different dry powder inhalers. The population pharmacokinetic analysis further explored the complex absorption and disposition characteristics of the two drugs. In case of inhaled FOR, a five-compartment PK model including an enterohepatic re-circulation process was developed. For inhaled BUD, the incorporation of two parallel first-order absorption rate constants (fast and slow) for lung absorption in a two-compartment PK model emphasized the importance of pulmonary anatomical features and underlying physiological processes during model development. The role of potential covariates on the variability of the PK parameters was also investigated.
During the 2014-2015 mutual events season, the Institut de Mécanique Céleste et de Calcul des Éphémérides (IMCCE), Paris, France, and the Sternberg Astronomical Institute (SAI), Moscow, Russia, led an international observation campaign to record ground-based photometric observations of Galilean moon mutual occultations and eclipses. We focused on processing the complete photometric observations data base to compute new accurate astrometric positions. We used our method to derive astrometric positions from the light curves of the events. We developed an accurate photometric model of mutual occultations and eclipses, while correcting for the satellite albedos, Hapke's light scattering law, the phase effect, and the limb darkening. We processed 609 light curves, and we compared the observed positions of the satellites with the theoretical positions from IMCCE NOE-5-2010-GAL satellite ephemerides and INPOP13c planetary ephemeris. The standard deviation after fitting the light curve in equatorial positions is ±24 mas, or 75 km at Jupiter. The rms (O-C) in equatorial positions is ±50 mas, or 150 km at Jupiter.
The geological, geomorphic conditions of a mountainous environment along with precipitation and human activities influence landslide occurrences. In many cases, their relation to landslide events is not well defined. The scope of the present study is to identify the influence of physical and anthropogenic factors in landslide activity. The study area is a mountainous part of the northern Peloponnesus in southern Greece. The existing landslides, lithology, slope angle, rainfall, two types of road network (highway-provincial roads and rural roads) along with land use of the study area are taken into consideration. Each physical and anthropogenic factor is further divided into sub-categories. Statistical analysis of landslide frequency and density, as well as frequency and density ratios, are applied and combined with a geographic information system (GIS) to evaluate the collected data and determine the relationship between physical and anthropogenic factors and landslide activity. The results prove that Plio-Pleistocene fine-grained sediments and flysch, relatively steep slopes (15°-30°) and a rise in the amount of rainfall increase landslide frequency and density. Additionally, Plio-Pleistocene fine-grained sediments and flysch, as well as schist chert formations, moderate (5°-15°) and relatively steep slopes (15°-30°), along with the amount of rainfall of > 700 mm are strongly associated with landslide occurrences. The frequency and magnitude of landslides increase in close proximity to roads. Their maximum values are observed within the 50 m buffer zone. This corresponds to a 100 m wide zone along with any type of road corridors, increasing landslide occurrences. In addition, a buffer zone of 75 m or 150 m wide zone along highway and provincial roads, as well as a buffer zone of 100 m or 200 m wide zones along rural roads, are strongly correlated with landslide events. The extensive cultivated land of the study area is strongly related to landslide activity. By contrast, urban areas are poorly related to landslides, because most of them are located in the northern coastal part of the study area where landslides are limited. The results provide information on physical and anthropogenic factors characterizing landslide events in the study area. The applied methodology rapidly estimates areas prone to landslides and it may be utilized for landslide hazard assessment mapping as well as for new and existing land use planning projects.
Wild or semi-wild edible greens (chórta) are an integral part of the traditional Greek Mediterranean diet due to their nutritional value, containing various phytonutrients beneficial to human health. Water-based decoctions of chórta are widely consumed in Greek alternative medicine as health promoting agents. This study examined the chemical profile of the decoctions of eight edible plants, Cichorium intybus, C. endivia, C. spinosum, Crepis sancta, Sonchus asper, Carthamus lanatus, Centaurea raphanina, and Amaranthus blitum, by UPLC-ESI-HRMS and HRMS/MS analysis, to determine possibly bioactive constituents. The profiles of the plants from the Asteraceae family are dominated by the presence of phenolic acids and flavonoid derivatives, whereas the A. blitum decoction is rich in triterpene saponins. Interestingly, the Centaurea raphanina decoction was found to be extremely rich in flavanones, particularly in the aglycone pinocembrin. Further phytochemical investigation and fractionation of this extract resulted in the isolation and identification of five compounds: phlorin (1), syringin (2), pinocembrin (3), pinocembroside (4), and pinocembrin-7-O-neohesperidoside (5). The extracts were also tested for their antioxidant and differential cytotoxic activity against tumor cells. C. raphanina was found to be differentially toxic against metastatic tumor cells. In conclusion, we found that Greek edible greens are a rich source of bioactive secondary metabolites and their consumption could contribute to the maintenance of overall health.
Plasmoids, overdense blobs of plasma containing magnetic fields and high-energy particles, are a self-consistent outcome of the reconnection process in the relativistic regime. Recent two-dimensional particle-in-cell (PIC) simulations have shown that plasmoids can undergo a variety of processes (e.g. mergers, bulk acceleration, growth, and advection) within the reconnection layer. We developed a Monte Carlo code, benchmarked with the recent PIC simulations, to examine the effects of these processes on the steady-state size and momentum distributions of the plasmoid chain. The differential plasmoid size distribution is shown to be a power law, ranging from a few plasma skin depths to ∼0.1 of the reconnection layer's length. The power-law slope is shown to be linearly dependent upon the ratio of the plasmoid acceleration and growth rates, which slightly decreases with increasing plasma magnetization. We perform a detailed comparison of our results with those of recent PIC simulations and briefly discuss the astrophysical implications of our findings through the representative case of flaring events from blazar jets.
The purpose of this study is to demonstrate whether and to what extent a single injection of platelet-rich plasma (PRP), under ultrasound guidance, can improve the clinical symptoms of patients with a mild to moderate carpal tunnel syndrome (CTS). We conducted a prospective, randomized, clinical study including 50 patients suffering from mild to moderate CTS for a minimum duration of 3 months. Patients were randomly divided into 2 groups: Group A (26 patients) received an ultrasound-guided PRP injection into the carpal tunnel, whereas Group B (24 patients) was injected with placebo (0.9% normal saline). The short- and mid-term outcomes were determined with the use of the Q-DASH questionnaire and the pain scale VAS administered at 0, 4, and 12 weeks follow-up. The success ratio was determined by the difference in the Q-DASH obtained pre-injection minus the final Q-DASH obtained after 12 weeks follow-up. Success was defined as a difference more than 25%. Group A patients demonstrated a 76.9% success as determined by the difference Q-DASH, whereas Group B patients demonstrated 33.3% success, which was significantly less than Group A (Χ , p = .011). The findings of this study suggest that a single PRP ultrasound-guided injection has positive effects in patients with CTS.
Various systematic reviews have recently shown that intra-articular platelet-rich plasma (IA-PRP) can lead to symptomatic relief of knee osteoarthritis for up to 12 months. There exist limited data on its use in small joints, such as the trapeziometacarpal joint (TMJ) or carpometacarpal joint (CMCJ) of the thumb. A prospective, randomized, blind, controlled, clinical trial of 33 patients with clinical and radiographic osteoarthritis of the TMJ (grades: I-III according to the Eaton and Littler classification) was conducted. Group A patients (16 patients) received 2 ultrasound-guided IA-PRP injections, while group B patients (17 patients) received 2 ultrasound-guided intra-articular methylprednisolone and lidocaine injections at a 2-week interval. Patients were evaluated prior to and at 3 and 12 months after the second injection using the visual analogue scale (VAS) 100/100, shortened Disabilities of the Arm, Shoulder, and Hand Questionnaire (Q-DASH), and patient's subjective satisfaction. No significant differences between the baseline clinical and demographic characteristics of the 2 groups were identified. After 12 months' follow-up, the IA-PRP treatment has yielded significantly better results in comparison with the corticosteroids, in terms of VAS score ( P = 0.015), Q-DASH score ( P = 0.025), and patients' satisfaction ( P = 0.002). Corticosteroids offer short-term relief of symptoms, but IA-PRP might achieve a lasting effect of up to 12 months in the treatment of early to moderate symptomatic TMJ arthritis.
As part of a network study of HIV infection among people who inject drugs (PWID) and their contacts, we discovered a connected subcomponent of 29 uninfected PWID. In the context of a just-declining large epidemic outbreak, this raised a question: What explains the existence of large pockets of uninfected people? Possible explanations include "firewall effects" (Friedman et al., 2000; Dombrowski et al., 2017) wherein the only HIV+ people that the uninfected take risks with have low viral loads; "bottleneck effects" wherein few network paths into the pocket of non-infection exist; low levels of risk behavior; and an impending outbreak. We considered each of these. Participants provided information on their enhanced sexual and injection networks and assisted us in recruiting network members. The largest connected component had 241 members. Data on risk behaviors in the last 6 months were collected at the individual level. Recent infection was determined by LAg (Sedia(TM) Biosciences Corporation), data on recent seronegative tests, and viral load. HIV RNA was quantified using Artus HI Virus-1 RG RT-PCR (Qiagen). The 29 members of the connected subcomponent of uninfected participants were connected (network distance = 1) to 17 recently-infected and 24 long-term infected participants. Fourteen (48%) of these 29 uninfected were classified as "extremely high risk" because they self-reported syringe sharing and had at least one injection partner with viral load >100,000 copies/mL who also reported syringe sharing. Seventeen of the 29 uninfected were re-interviewed after 6 months, but none had seroconverted. These findings show the power of network research in discovering infection patterns that standard individual-level studies cannot. Theoretical development and exploratory network research studies may be needed to understand these findings and deepen our understanding of how HIV does and does not spread through communities. Finally, the methods developed here provide practical tools to study "bottleneck" and "firewall" network hypotheses in practice.
Aim: To evaluate the biomization technique for reconstructing past vegetation in the Eastern Mediterranean–Black Sea–Caspian-Corridor using an extensive modern pollen data set and comparing reconstructions to potential vegetation and observed land cover data. Location: The region between 28–48°N and 22–62°E. Methods: We apply the biomization technique to 1,387 modern pollen samples, representing 1,107 entities, to reconstruct the distribution of 13 broad vegetation categories (biomes). We assess the results using estimates of potential natural vegetation from the European Vegetation Map and the Physico-Geographic Atlas of the World. We test whether anthropogenic disturbance affects reconstruction quality using land use information from the Global Land Cover data set. Results: The biomization scheme successfully predicts the broadscale patterns of vegetation across the region, including changes with elevation. The technique discriminates deserts from shrublands, the prevalence of woodlands in moister lowland sites, and the presence of temperate and mixed forests at higher elevations. Quantitative assessment of the reconstructions is less satisfactory: the biome is predicted correctly at 44% of the sites in Europe and 33% of the sites overall. The low success rate is not a reflection of anthropogenic impacts: only 33% of the samples are correctly assigned after the removal of sites in anthropogenically altered environments. Open vegetation is less successfully predicted (33%) than forest types (73%), reflecting the under-representation of herbaceous taxa in pollen assemblages and the impact of long-distance pollen transport into open environments. Samples from small basins ( < 1 km 2 ) are more likely to be reconstructed accurately, with 58% of the sites in Europe and 66% of all sites correctly predicted, probably because they sample an appropriate pollen source area to reflect regional vegetation patterns in relatively heterogeneous landscapes. While methodological biases exist, the low confidence of the quantitative comparisons should not be over-emphasized because the target maps themselves are not accurate representations of vegetation patterns in this region. Main Conclusions: The biomization scheme yields reasonable reconstructions of the broadscale vegetation patterns in the Eastern Mediterranean–Black Sea–Caspian-Corridor, particularly if appropriate-sized sampling sites are used. Our results indicate biomization could be used to reconstruct changing patterns of vegetation in response to past climate changes in this region.
The synthesis and characterisation of a new anionic flexible scorpionate ligand, methyl(bis-7-azaindolyl)borohydride [MeBai]- is reported herein. The ligand was coordinated to a series of group nine transition metal centres forming the complexes, [Ir(MeBai)(COD)] (1), [Rh(MeBai)(COD)] (2), [Rh(MeBai)(CODMe)] (2-Me) and [Rh(MeBai)(NBD)] (3), where COD = 1,5-cyclooctadiene, CODMe = 3-methyl-1,5-cyclooctadiene and NBD = 2,5-norbornadiene. In all cases, the boron based ligand was found to bind to the metal centres via a κ3-N,N,H coordination mode. The ligand and complexes were fully characterised by spectroscopic and analytical methods. The structures of the ligand and three of the complexes were confirmed by X-ray crystallography. The potential for migration of the "hydride" or "methyl" units from boron to the metal centre was also explored. During these studies an unusual transformation, involving the oxidation of the rhodium centre, was observed in complex 2. In this case, the η4-COD unit transformed into a η1,η3-C8H12 unit where the ring was bound via one sigma bond and one allyl unit. This is the first time such a transformation has been observed at a rhodium centre.
Georgiou A, Prapa A, Papatheodoridis G, Deutsch M, Alexopoulou A, Vlachogiannakos J, Ioannidou P, Papageorgiou M-V, Papadopoulos N, Karagiannakis D, et al.Prevalence of malnutrition in a sample of cirrhotic patients. Clinical Nutrition. 2018;37:S63–S64.
The mammalian neocortex has undergone remarkable changes through evolution. A consequence of such rapid evolutionary events could be a trade-off that has rendered the brain susceptible to certain neurodevelopmental and neuropsychiatric conditions. We analyzed the exomes of 65 patients with the structural brain malformation periventricular nodular heterotopia (PH). De novo coding variants were observed in excess in genes defining a transcriptomic signature of basal radial glia, a cell type linked to brain evolution. In addition, we located two variants in human isoforms of two genes that have no ortholog in mice. Modulating the levels of one of these isoforms for the gene PLEKHG6 demonstrated its role in regulating neuroprogenitor differentiation and neuronal migration via RhoA, with phenotypic recapitulation of PH in human cerebral organoids. This suggests that this PLEKHG6 isoform is an example of a primate-specific genomic element supporting brain development.
The liar and kindred paradoxes show that we can derive contradictions if our language possesses sentences lending themselves to paradox and we reason classically from schema (T) about truth:
S is true iff p,
where the letter p is to be replaced with a sentence and the letter S with a name of that sentence. This article presents a theory of truth that keeps (T) at the expense of classical logic. The theory is couched in a language that possesses paradoxical sentences. It incorporates all the instances of the analogue of (T) for that language and also includes other platitudes about truth. The theory avoids contradiction because its logical framework is an appropriately constructed nonclassical propositional logic. The logic and the theory are different from others that have been proposed for keeping (T), and the methods used in the main proofs are novel.
Background: Senescence is a fundamental biological process implicated in various pathologies, including cancer. Regarding carcinogenesis, senescence signifies, at least in its initial phases, an anti-tumor response that needs to be circumvented for cancer to progress. Micro-RNAs, a subclass of regulatory, non-coding RNAs, participate in senescence regulation. At the subcellular level micro-RNAs, similar to proteins, have been shown to traffic between organelles influencing cellular behavior. The differential function of micro-RNAs relative to their subcellular localization and their role in senescence biology raises concurrent in situ analysis of coding and non-coding gene products in senescent cells as a necessity. However, technical challenges have rendered in situ co-detection unfeasible until now. Methods: In the present report we describe a methodology that bypasses these technical limitations achieving for the first time simultaneous detection of both a micro-RNA and a protein in the biological context of cellular senescence, utilizing the new commercially available SenTraGorTM compound. The method was applied in a prototypical human non-malignant epithelial model of oncogene-induced senescence that we generated for the purposes of the study. For the characterization of this novel system, we applied a wide range of cellular and molecular techniques, as well as high-throughput analysis of the transcriptome and micro-RNAs. Results: This experimental setting has three advantages that are presented and discussed: i) it covers a "gap" in the molecular carcinogenesis field, as almost all corresponding in vitro models are fibroblast-based, even though the majority of neoplasms have epithelial origin, ii) it recapitulates the precancerous and cancerous phases of epithelial tumorigenesis within a short time frame under the light of natural selection and iii) it uses as an oncogenic signal, the replication licensing factor CDC6, implicated in both DNA replication and transcription when over-expressed, a characteristic that can be exploited to monitor RNA dynamics. Conclusions: Consequently, we demonstrate that our model is optimal for studying the molecular basis of epithelial carcinogenesis shedding light on the tumor-initiating events. The latter may reveal novel molecular targets with clinical benefit. Besides, since this method can be incorporated in a wide range of low, medium or high-throughput image-based approaches, we expect it to be broadly applicable.
The aim of this work is to develop a gastrointestinal (GI) drug absorption model based on a reaction limited model of dissolution and consider its impact on the biopharmaceutic classification of drugs. Estimates for the fraction of dose absorbed as a function of dose, solubility, reaction/dissolution rate constant and the stoichiometry of drug-GI fluids reaction/dissolution were derived by numerical solution of the model equations. The undissolved drug dose and the reaction/dissolution rate constant drive the dissolution rate and determine the extent of absorption when high-constant drug permeability throughout the gastrointestinal tract is assumed. Dose is an important element of drug-GI fluids reaction/dissolution while solubility exclusively acts as an upper limit for drug concentrations in the lumen. The 3D plots of fraction of dose absorbed as a function of dose and reaction/dissolution rate constant for highly soluble and low soluble drugs for different ``stoichiometries{''} (0.7, 1.0, 2.0) of the drug-reaction/dissolution with the GI fluids revealed that high extent of absorption was found assuming high drug-reaction/dissolution rate constant and high drug solubility. The model equations were used to simulate in vivo supersaturation and precipitation phenomena. The model developed provides the theoretical basis for the interpretation of the extent of drug's absorption on the basis of the parameters associated with the drug-GI fluids reaction/dissolution. A new paradigm emerges for the biopharmaceutic classification of drugs, namely, a model independent biopharmaceutic classification scheme of four drug categories based on either the fulfillment or not of the current dissolution criteria and the high or low % drug metabolism.
Vegetation patterns during the 1st millennium AD in the central Mediterranean, exhibit a great variability, due to the richness of these habitats and the continuous shaping of the environment by human societies. Variations in land use, witnessed in the pollen record, reflect the role that local vegetation and environmental conditions played in the choices made by local societies. The interdisciplinary study of off-site cores remains the key evidence for palaeoenvironmental transformations mirroring the ‘semi-natural’ vegetation, and revealing temporal fluctuations and the amount of human impact on a regional scale.
HSPB6/Hsp20 (heat shock protein family B [small] member 6) has emerged as a novel cardioprotector against stress-induced injury. We identified a human mutant of HSPB6 (HSPB6(S10F)) exclusively present in dilated cardiomyopathy (DCM) patients. Cardiac expression of this mutant in mouse hearts resulted in remodeling and dysfunction, which progressed to heart failure and early death. These detrimental effects were associated with reduced interaction of mutant HSPB6(S10F) with BECN1/Beclin 1, leading to BECN1 ubiquitination and its proteosomal degradation. As a result, autophagy flux was substantially inhibited and apoptosis was increased in HSPB6(S10F)-mutant hearts. In contrast, overexpression of wild-type HSPB6 (HSPB6 WT) not only increased BECN1 levels, but also competitively suppressed binding of BECN1 to BCL2, resulting in stimulated autophagy. Indeed, preinhibition of autophagy attenuated the cardioprotective effects of HSPB6 WT. Taken together, these findings reveal a new regulatory mechanism of HSPB6 in cell survival through its interaction with BECN1. Furthermore, Ser10 appears to be crucial for the protective effects of HSPB6 and transversion of this amino acid to Phe contributes to cardiomyopathy.
Characterization of the least number of muscle fibers analyzed for a quick and reliable, evaluation of intramuscular fiber conduction velocity (MFCV) is of importance for sport scientists. The aim of this study was to evaluate the reliability of vastus lateralis' intramuscular MFCV measuring either 25 or 50 different muscle fibers per participant, as well as to compare intramuscular MFCV measured in 25 (C ), 50 (C ), or 140 (C ) muscle fibers. Resting vastus lateralis' MFCV was measured in 21 young healthy males (age 22.1±2.4 years) using intramuscular microelectrodes in different days. Test-retest reliability of MFCV's parameters was calculated for C and C , while MFCV was compared among C , C , and C . Significant differences of MFCV parameters were observed between C condition and those of C and C . The differences in MFCV values between conditions C and C were non-significant. A close correlation was found for MFCV between C and C (r=0.884-0.988, P=.000). All reliability measures of MFCV measured with 50 fibers were high (eg, ICC=0.813-0.980, P=.000), in contrast to C (eg, ICC=0.023-0.580 P>.05). In conclusion, an average of 50 different fibers per subject is sufficient to provide a quick and reliable intramuscular evaluation of vastus lateralis MFCV.
BACKGROUND: Radiographic fracture classification helps with research on prognosis and treatment. AO/OTA classification into fracture type has shown to be reliable, but further classification of fractures into subgroups reduces the interobserver agreement and takes a considerable amount of practice and experience in order to master.
QUESTIONS/PURPOSES: We assessed: (1) differences between more and less experienced trauma surgeons based on hip fractures treated per year, years of experience, and the percentage of their time dedicated to trauma, (2) differences in the interobserver agreement between classification into fracture type, group, and subgroup, and (3) differences in the interobserver agreement when assessing fracture stability compared to classifying fractures into type, group and subgroup.
METHODS: This study used the Science of Variation Group to measure factors associated with variation in interobserver agreement on classification of proximal femur fractures according to the AO/OTA classification on radiographs. We selected 30 anteroposterior radiographs from 1061 patients aged 55 years or older with an isolated fracture of the proximal femur, with a spectrum of fracture types proportional to the full database. To measure the interobserver agreement the Fleiss' kappa was determined and bootstrapping (resamples = 1000) was used to calculate the standard error, z statistic, and 95% confidence intervals. We compared the Kappa values of surgeons with more experience to less experienced surgeons.
RESULTS: There were no statistically significant differences in the Kappa values on each classification level (type, group, subgroup) between more and less experienced surgeons. When all surgeons were combined into one group, the interobserver reliability was the greatest for classifying the fractures into type (kappa, 0.90; 95% CI, 0.83 to 0.97; p < 0.001), reflecting almost perfect agreement. When comparing the kappa values between classes (type, group, subgroup), we found statistically significant differences between each class. Substantial agreement was found in the clinically relevant groups stable/unstable trochanteric, displaced/non-displaced femoral neck, and femoral head fractures (kappa, 0.60; 95% CI, 0.53 to 0.67, p < 0.001).
CONCLUSIONS: This study adds to a growing body of evidence that relatively simple distinctions are more reliable and that this is independent of surgeon experience.
B[e] supergiants are luminous evolved massive stars. The mass-loss during this phase creates a complex circumstellar environment with atomic, molecular, and dusty regions usually found in rings or disc-like structures. For a better comprehension of the mechanisms behind the formation of these rings, detailed knowledge about their structure and dynamics is essential. To address that, we obtained high-resolution optical and near-infrared (near-IR) spectra for eight selected Galactic B[e] supergiants, for which CO emission has been detected. Assuming Keplerian rotation for the disc, we combine the kinematics obtained from the CO bands in the near-IR with those obtained by fitting the forbidden emission [O I] λ5577, [O I] λλ6300,6363, and [Ca II] λλ7291,7323 lines in the optical to probe the disc structure. We find that the emission originates from multiple ring structures around all B[e] supergiants, with each one of them displaying a unique combination of rings regardless of whether the object is part of a binary system. The confirmed binaries display spectroscopic variations of their line intensities and profiles as well as photometric variability, whereas the ring structures around the single stars are stable.
Nicotinamide phosphoribosyl-transferase (Nampt) or pre-B cell colony-enhancing factor or visfatin represents a pleiotropic molecule acting as an enzyme, a cytokine and a growth factor. Intracellular Nampt plays an important role in cellular bioenergetics and metabolism, particularly NAD biosynthesis. NAD biosynthesis is critical in DNA repair, oncogenic signal transduction, transcription, genomic integrity and apoptosis. Although its insulin-mimetic function remains a controversial issue, extracellular Nampt presents proliferative, anti-apoptotic, pro-inflammatory, pro-angiogenic and metastatic properties. Nampt is upregulated in many malignancies, including obesity-associated cancers, and is associated with worse prognosis. Serum Nampt may be a potential diagnostic and prognostic biomarker in cancer. Pharmacologic agents that neutralize Nampt or medications that decrease Nampt levels or downregulate signaling pathways downstream of Nampt may prove to be useful anti-cancer treatments. In particular, Nampt inhibitors as monotherapy or in combination therapy have displayed anti-cancer activity in vivo and in vitro. The aim of this review is to explore the role of Nampt in cancer pathophysiology as well as to synopsize the mechanisms underlying the association between extracellular and intracellular Nampt, and malignancy. Exploring the interplay of cellular bioenergetics, inflammation and adiposopathy is expected to be of importance in the development of preventive and therapeutic strategies against cancer.
Mitochondria are cellular organelles essential for multiple biological processes, including energy production, metabolites biosynthesis, cell death, and immunological responses among others. Recent advances in the field of immunology research reveal the pivotal role of energy metabolism in innate immune cells fate and function. Therefore, the maintenance of mitochondrial network integrity and activity is a prerequisite for immune system homeostasis. Mitochondrial selective autophagy, known as mitophagy, surveils mitochondrial population eliminating superfluous and/or impaired organelles and mediating cellular survival and viability in response to injury/trauma and infection. Defective removal of damaged mitochondria leads to hyperactivation of inflammatory signaling pathways and subsequently to chronic systemic inflammation and development of inflammatory diseases. Here, we review the molecular mechanisms of mitophagy and highlight its critical role in the innate immune system homeostasis.
