A critical discussion of how psychological and biological factors influence the development of anxiety disorders.

Anxiety disorders are becoming a common symptom, with the number of people affected by them rapidly multiplying. Numerous studies try to explain their nature, yet there are no clear answer so far as to what exactly causes them. Up to date bibliography on psychological and biological factors possibly correlating with anxiety disorders, with a focus on genes, chromosomes, proteins, HPA axis, serotonin, the environment and even maternal care are critically discussed

New lessons on TDP-43 from old N. furzeri killifish

Frontotemporal dementia and amyotrophic lateral sclerosis are fatal and incurable neurodegenerative diseases linked to the pathological aggregation of the TDP-43 protein. This is an essential DNA/RNA-binding protein involved in transcription regulation, pre-RNA processing, and RNA transport. Having suitable animal models to study the mechanisms of TDP-43 aggregation is crucial to develop treatments against disease. We have previously demonstrated that the killifish Nothobranchius furzeri offers the advantage of being the shortest-lived vertebrate with a clear aging phenotype. Here, we show that the two N. furzeri paralogs of TDP-43 share high sequence homology with the human protein and recapitulate its cellular and biophysical behavior. During aging, N. furzeri TDP-43 spontaneously forms insoluble intracellular aggregates with amyloid characteristics and colocalizes with stress granules. Our results propose this organism as a valuable new model of TDP-43-related pathologies making it a powerful tool for the study of disease mechanism

Selection and Modelling of a New Single-Domain Intrabody Against TDP-43

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder associated to deteriorating motor and cognitive functions, and short survival. The disease is caused by neuronal death which results in progressive muscle wasting and weakness, ultimately leading to lethal respiratory failure. The misbehaviour of a specific protein, TDP-43, which aggregates and becomes toxic in ALS patient’s neurons, is supposed to be one of the causes. TDP-43 is a DNA/RNA-binding protein involved in several functions related to nucleic acid metabolism. Sequestration of TDP-43 aggregates is a possible therapeutic strategy that could alleviate or block pathology. Here, we describe the selection and characterization of a new intracellular antibody (intrabody) against TDP-43 from a llama nanobody library. The structure of the selected intrabody was predicted in silico and the model was used to suggest mutations that enabled to improve its expression yield, facilitating its experimental validation. We showed how coupling experimental methodologies with in silico design may allow us to obtain an antibody able to recognize the RNA binding regions of TDP-43. Our findings illustrate a strategy for the mitigation of TDP-43 proteinopathy in ALS and provide a potential new tool for diagnostics

'I think that it's a pain in the ass that I have to stand outside in the cold and have a cigarette': representations of smoking and experiences of disapproval in UK and Greek smokers

Smokers in Greece and the UK are habitually exposed to different levels of social disapproval. This qualitative study explored the accounts of smoking and disapproval offered by 32 UK and Greek smokers. Accounts were framed with reference to a highly moralized construction of smoking. Participants were sensitive to social disapproval of their smoking. While disapproval from those close to them was accepted, disapproval from the general public was not. Two discursive repertories 'smoking works for me now' and 'the struggle to quit' were identified as resources that participants drew upon to enable continued smoking while acknowledging the health issues. While there were many similarities in the accounts provided, there were important differences that seem to reflect the different 'smoking worlds' inhabited. Copyright 2006 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution

'I think that it's a pain in the ass that I have to stand outside in the cold and have a cigarette': representations of smoking and experiences of disapproval in UK and Greek smokers

Smokers in Greece and the UK are habitually exposed to different levels of social disapproval. This qualitative study explored the accounts of smoking and disapproval offered by 32 UK and Greek smokers. Accounts were framed with reference to a highly moralized construction of smoking. Participants were sensitive to social disapproval of their smoking. While disapproval from those close to them was accepted, disapproval from the general public was not. Two discursive repertories 'smoking works for me now' and 'the struggle to quit' were identified as resources that participants drew upon to enable continued smoking while acknowledging the health issues. While there were many similarities in the accounts provided, there were important differences that seem to reflect the different 'smoking worlds' inhabited. Copyright 2006 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution

Meta-Analysis Design and Results in Real Life: Problem Solvers or Detour to Maze. A Critical Review of Meta-Analysis of DAPT Randomized Controlled Trials.

Therapeutic strategies - such as duration of dual antiplatelet therapy after coronary artery stenting - usually generate a large quantity of meta-analyses. The meta-analyses that include the same randomized clinical trials should produce similar results. Our aim in the study is to analyze the quality and to compare the results of meta-analyses focused on a controversial topic such as dual antiplatelet therapy after percutaneous coronary intervention. We searched all published meta-analyses published up to November 2015 (near DAPT trial publication) selecting those that included the same randomized clinical trials comparing patterns of briefer versus longer-term double antiplatelet therapy. Seventeen meta-analyses achieved our selection criteria. Of the seventeen analyzed, we identified seven (41.1%) based on the same ten randomized clinical trials (RCTs), yet their results varied widely. Many of the meta-analyses differed in only some minor aspect of the design (i.e. eligible studies, length of comparators and statistical methods used). Some authors differed in the number of patients participating in RCTs and even, despite reviewing the same underlying trials, only 2 of the 7 meta-analyses included the same number of patients. Meta-analyses around cardiovascular, all-cause or non-cardiovascular death differ frequently. In the DAPT duration setting, several meta-analyses have been recently published based on the same data, presenting several issues making it difficult to determine clear recommendations on certain points.IN receives research funding from Astrazeneca; has received minor consulting fees from Boston, Medtronic, Astrazeneca; and speaking fees or support for attending scientificmeetings fromBoehringer, Daiichi-Sankyo, Lilly, AstraZeneca and Pfizer. AE is Astrazeneca employee. HB receives research funding from the Instituto de Salud Carlos III (PIE16/00021), AstraZeneca, BMS, Janssen and Novartis; has received consulting fees from Abbott, AstraZeneca, Bayer, BMS-Pfizer, Novartis; and speaking fees or support for attending scientificmeetings from AstraZeneca, Bayer, BMS-Pfizer, Ferrer, Novartis, Servier and MEDSCAPE-the heart.og. The other authors pose no relevant disclosures regarding this manuscript.S