Efficacy of new-generation antidepressants assessed with the Montgomery-Asberg depression rating scale, the gold standard clinician rating scale : a meta-analysis of randomised placebo-controlled trials

It has been claimed that efficacy estimates based on the Hamilton Depression Rating-Scale (HDRS) underestimate antidepressants true treatment effects due to the instrument's poor psychometric properties. The aim of this study is to compare efficacy estimates based on the HDRS with the gold standard procedure, the Montgomery-Asberg Depression Rating-Scale (MADRS)

Quantifying protein densities on cell membranes using super-resolution optical fluctuation imaging

Surface molecules, distributed in diverse patterns and clusters on cell membranes, influence vital functions of living cells. It is therefore important to understand their molecular surface organisation under different physiological and pathological conditions. Here, we present a model-free, quantitative method to determine the distribution of cell surface molecules based on TIRF illumination and super-resolution optical fluctuation imaging (SOFI). This SOFI-based approach is robust towards single emitter multiple-blinking events, high labelling densities and high blinking rates. In SOFI, the molecular density is not based on counting events, but results as an intrinsic property due to the correlation of the intensity fluctuations. The effectiveness and robustness of the method was validated using simulated data, as well as experimental data investigating the impact of palmitoylation on CD4 protein nanoscale distribution in the plasma membrane of resting T cells.Comment: 9 pages, 3 figures plus Supplementary Informatio

Comparing the effects of repetitive transcranial magnetic stimulation and electroconvulsive therapy in the treatment of depression : a systematic review and meta-analysis

Electroconvulsive therapy (ECT) is the longest standing psychiatric treatment available and has unequivocal benefit in severe depression. However this treatment comes with a number of side effects such as memory impairment. On the other hand, Repetitive Transcranial Magnetic Stimulation (rTMS) is a relatively new form of treatment which has been shown to be efficacious in patients suffering from a number of psychopathologies, including severe depression, with few reported side effects. Due to its potential therapeutic efficacy and lack of side effects, rTMS has gained traction in the treatment of depression, with a number of authors keen to see it take over from ECT. However, it is not clear whether rTMS represents a therapeutic alternative to ECT. This meta-analysis will therefore compare the "gold standard" treatment for severe depression, with the relatively new but promising rTMS. A literature search will be performed with the intention to include all randomised clinical trials. The null hypothesis is that there is no difference in the antidepressant efficacy between the two types of treatment modalities. Statistical analysis of Hamilton Depression Rating Scale (HDRS) scores will be performedpeer-reviewe

Selection and environmental adaptation along a path to speciation in the Tibetan frog Nanorana parkeri.

Tibetan frogs, Nanorana parkeri, are differentiated genetically but not morphologically along geographical and elevational gradients in a challenging environment, presenting a unique opportunity to investigate processes leading to speciation. Analyses of whole genomes of 63 frogs reveal population structuring and historical demography, characterized by highly restricted gene flow in a narrow geographic zone lying between matrilines West (W) and East (E). A population found only along a single tributary of the Yalu Zangbu River has the mitogenome only of E, whereas nuclear genes of W comprise 89-95% of the nuclear genome. Selection accounts for 579 broadly scattered, highly divergent regions (HDRs) of the genome, which involve 365 genes. These genes fall into 51 gene ontology (GO) functional classes, 14 of which are likely to be important in driving reproductive isolation. GO enrichment analyses of E reveal many overrepresented functional categories associated with adaptation to high elevations, including blood circulation, response to hypoxia, and UV radiation. Four genes, including DNAJC8 in the brain, TNNC1 and ADORA1 in the heart, and LAMB3 in the lung, differ in levels of expression between low- and high-elevation populations. High-altitude adaptation plays an important role in maintaining and driving continuing divergence and reproductive isolation. Use of total genomes enabled recognition of selection and adaptation in and between populations, as well as documentation of evolution along a stepped cline toward speciation

Maintenance deep transcranial magnetic stimulation sessions are associated with reduced depressive relapses in patients with unipolar or bipolar depression

Introduction: Deep transcranial magnetic stimulation (dTMS) is a new form of TMS allowing safe stimulation of deep brain regions. The objective of this preliminary study was to assess the role of dTMS maintenance sessions in protecting patients with bipolar disorder (BD) or recurrent major depressive disorder (MDD) from developing depressive or manic relapses in a 12-month follow-up period. Methods: Twenty-four drug-resistant patients with a current depressive episode and a diagnosis of MDD or BD have been enrolled in the study. All the participants underwent daily dTMS sessions for 4 weeks. One group (maintenance - M group) received additional maintenance dTMS sessions weekly or twice a week. Results: After the first dTMS cycle, a significant reduction of Hamilton Depression Rating Scale (HDRS) scores was observed in all participants. Subsequently, the HDRS mean scores did not significantly change over time in the M group, while it significantly increased in the non-M-group after 6 and 12 months. Discussion: This study confirms previous evidence of a positive therapeutic effect of dTMS on depressive symptoms and suggests that, after recovery from acute episodes, maintenance dTMS sessions may be helpful in maintaining euthymia in a 12-month follow-up period

X-ray Spectral Signatures of the Photon Bubble Model for Ultraluminous X-ray Sources

The nature of ultraluminous X-ray sources in nearby galaxies is one of the major open questions in modern X-ray astrophysics. One possible explanation for these objects is an inhomogeneous, radiation dominated accretion disk around a $\sim 10 M_{\odot}$ black hole -- the so-called ``photon bubble'' model. While previous studies of this model have focused primarily on its radiation-hydrodynamics aspects, in this paper, we provide an analysis of its X-ray spectral (continuum and possible edge and line) characteristics. Compton reflection between high and low density regions in the disk may provide the key to distinguishing this model from others, such as accretion onto an intermediate mass black hole. We couple a Monte Carlo/Fokker-Planck radiation transport code with the XSTAR code for reflection to simulate the photon spectra produced in a photon bubble model for ULXs. We find that reflection components tend to be very weak and in most cases not observable, and make predictions for the shape of the high-energy Comptonizing spectra. In many cases the Comptonization dominates the spectra even down to $\sim$ a few keV. In one simulation, a \sim 9 \kev feature was found, which may be considered a signature of photon bubbles in ULXs; furthermore, we make predictions of high energy power-laws which may be observed by future instruments.Comment: Accepted for publication in the Astrophysical Journa

Accelerated intermittent theta burst stimulation for suicide risk in therapy-resistant depressed patients : a randomized, sham-controlled trial

Objectives: We aimed to examine the effects and safety of accelerated intermittent Theta Burst Stimulation (iTBS) on suicide risk in a group of treatment-resistant unipolar depressed patients, using an extensive suicide assessment scale. Methods: In 50 therapy-resistant, antidepressant-free depressed patients, an intensive protocol of accelerated iTBS was applied over the left dorsolateral prefrontal cortex (DLPFC) in a randomized, sham-controlled crossover design. Patients received 20 iTBS sessions over 4 days. Suicide risk was assessed using the Beck Scale of Suicide ideation (BSI). Results: The iTBS protocol was safe and well tolerated. We observed a significant decrease of the BSI score over time, unrelated to active or sham stimulation and unrelated to depression-response. No worsening of suicidal ideation was observed. The effects of accelerated iTBS on mood and depression severity are reported in Duprat et al. (2016). The decrease in suicide risk lasted up to 1 month after baseline, even in depression non-responders. Conclusions: This accelerated iTBS protocol was safe. The observed significant decrease in suicide risk was unrelated to active or sham stimulation and unrelated to depression response. Further sham-controlled research in suicidal depressed patients is necessary. (Clinicaltrials.gov identifier: NCT01832805)

Usual energy and macronutrient intakes in 2-9-year-old European children

OBJECTIVE: Valid estimates of population intakes are essential for monitoring trends as well as for nutritional interventions, but such data are rare in young children. In particular, the problem of misreporting in dietary data is usually not accounted for. Therefore, this study aims to provide accurate estimates of intake distributions in European children. DESIGN: Cross-sectional setting-based multi-centre study. SUBJECTS: A total of 9560 children aged 2-9 years from eight European countries with at least one 24-h dietary recall (24-HDR). METHODS: The 24-HDRs were classified in three reporting groups based on age- and sex-specific Goldberg cutoffs (underreports, plausible reports, overreports). Only plausible reports were considered in the final analysis (N=8611 children). The National Cancer Institute (NCI)-Method was applied to estimate population distributions of usual intakes correcting for the variance inflation in short-term dietary data. RESULTS: The prevalence of underreporting (9.5%) was higher compared with overreporting (3.4%). Exclusion of misreports resulted in a shift of the energy and absolute macronutrient intake distributions to the right, and further led to the exclusion of extreme values, that is, mean values and lower percentiles increased, whereas upper percentiles decreased. The distributions of relative macronutrient intakes (% energy intake from fat/carbohydrates/proteins) remained almost unchanged when excluding misreports. Application of the NCI-Method resulted in markedly narrower intake distributions compared with estimates based on single 24-HDRs. Mean percentages of usual energy intake from fat, carbohydrates and proteins were 32.2, 52.1 and 15.7%, respectively, suggesting the majority of European children are complying with common macronutrient intake recommendations. In contrast, total water intake (mean: 1216.7 ml per day) lay below the recommended value for >90% of the children. CONCLUSION: This study provides recent estimates of intake distributions of European children correcting for misreporting as well as for the daily variation in dietary data. These data may help to assess the adequacy of young children's diets in Europe