Ravncombs3991

The inverse weighted method revealed no associations of AD on broad depression [odds ratio (OR) 1·014; P=0·431], probable MDD (OR 1·002; P=0·568), International Classification of Diseases, Ninth/Tenth Revision-based MDD (OR 1·001; P=0·466) or anxiety (OR 1·097; P=0·180).

This MR study does not support a causal effect of AD on depression and anxiety.

This MR study does not support a causal effect of AD on depression and anxiety.

Local anaesthetics block sodium and a variety of potassium channels. Although previous studies identified a residue in the pore signature sequence together with three residues in the S6 segment as a putative binding site, the precise molecular basis of inhibition of K

channels by local anaesthetics remained unknown. Crystal structures of K

channels predict that some of these residues point away from the central cavity and face into a drug binding site called side pockets. Thus, the question arises whether the binding site of local anaesthetics is exclusively located in the central cavity or also involves the side pockets.

A systematic functional alanine mutagenesis approach, scanning 58 mutants, together with in silico docking experiments and molecular dynamics simulations was utilized to elucidate the binding site of bupivacaine and ropivacaine.

Inhibition of K

1.5 channels by local anaesthetics requires binding to the central cavity and the side pockets, and the latter requires interactions with residues of the S5 and the back of the S6 segments. Danicamtiv order Mutations in the side pockets remove stereoselectivity of inhibition of K

1.5 channels by bupivacaine. Although binding to the side pockets is conserved for different local anaesthetics, the binding mode in the central cavity and the side pockets shows considerable variations.

Local anaesthetics bind to the central cavity and the side pockets, which provide a crucial key to the molecular understanding of their K

channel affinity and stereoselectivity, as well as their spectrum of side effects.

Local anaesthetics bind to the central cavity and the side pockets, which provide a crucial key to the molecular understanding of their Kv channel affinity and stereoselectivity, as well as their spectrum of side effects.Oxysterols have gained attention over the last decades and are now considered as fully fledged bioactive lipids. The study of their levels in several conditions, including atherosclerosis, obesity and neurodegenerative diseases, led to a better understanding of their involvement in (patho)physiological processes such as inflammation and immunity. For instance, the characterization of the cholesterol-7α,25-dihydroxycholesterol/GPR183 axis and its implication in immunity represents an important step in the oxysterome study. Besides this axis, others were identified as important in several inflammatory pathologies (such as colitis, lung inflammation and atherosclerosis). However, the oxysterome is a complex system notably due to a redundancy of metabolic enzymes and a wide range of receptors. Indeed, deciphering oxysterol roles and identifying the potential receptor(s) involved in a given pathology remain challenging. Oxysterol properties are very diverse, but most of them could be connected by a common component inflammation. Here, we review the implication of oxysterol receptors in inflammatory diseases.Despite the progress in characterising the pharmacological profile of drugs of abuse, their precise biochemical impact remains unclear. The metabolome reflects the multifaceted biochemical processes occurring within a biological system. This includes those encoded in the genome but also those arising from environmental/exogenous exposures and interactions between the two. Using metabolomics, the biochemical derangements associated with substance abuse can be determined as the individual transitions from recreational drug to chronic use (dependence). By understanding the biomolecular perturbations along this time course and how they vary across individuals, metabolomics can elucidate biochemical mechanisms of the addiction cycle (dependence/withdrawal/relapse) and predict prognosis (recovery/relapse). In this review, we summarise human and animal metabolomic studies in the field of opioid and psychostimulant addiction. We highlight the importance of metabolomics as a powerful approach for biomarker discovery and its potential to guide personalised pharmacotherapeutic strategies for addiction targeted towards the individual's metabolome.

Catheter ablation of atrial fibrillation in heart failure seems to be the way to improve the quality of life, life expectance, and prognosis. In this review, we outline the growing role of this therapy and which patients can benefit from it.

While previous studies comparing rate control and rhythm control had not demonstrated the superiority of rhythm control in the prognosis of patients with atrial fibrillation and heart failure, recent findings seem to demonstrate that catheter ablation of atrial fibrillation reduces mortality and hospitalization for heart failure and improves the quality of life, when compared to medical therapy alone. An early rhythm-control strategy in atrial fibrillation may reduce cardiovascular death, stroke, hospitalization for HF, or acute coronary syndrome. Catheter ablation in heart failure is an effective and safe solution to obtain a rhythm control and, therefore, to improve outcomes. A better selection of the patients could help to avoid futile procedures and to identify patients requiring a closer follow-up, to redo procedures, or the addition of antiarrhythmic drugs.

While previous studies comparing rate control and rhythm control had not demonstrated the superiority of rhythm control in the prognosis of patients with atrial fibrillation and heart failure, recent findings seem to demonstrate that catheter ablation of atrial fibrillation reduces mortality and hospitalization for heart failure and improves the quality of life, when compared to medical therapy alone. An early rhythm-control strategy in atrial fibrillation may reduce cardiovascular death, stroke, hospitalization for HF, or acute coronary syndrome. Catheter ablation in heart failure is an effective and safe solution to obtain a rhythm control and, therefore, to improve outcomes. A better selection of the patients could help to avoid futile procedures and to identify patients requiring a closer follow-up, to redo procedures, or the addition of antiarrhythmic drugs.

Despite primary percutaneous coronary intervention (PPCI) is generally considered the best therapy in older frail adults with ST-segment elevation myocardial infarction (STEMI), the incidence of re-hospitalization for cardiovascular diseases remains significant in these patients.

We hypothesized that thrombus aspiration (TA) before PPCI could be a useful treatment for reducing mortality and rehospitalizations in frail patients undergoing PPCI for STEMI.

We conducted a study comparing PPCI alone vs TA + PPCI in frail STEMI patients. We examined a cohort of consecutive frail patients aged ≥ 65years with first STEMI treated with PPCI between February 2008 and July 2015 at the Department of Cardiology of the "Cardarelli" Hospital in Naples, Italy.

The study was completed by 389 patients (PPCI 195, TA + PPCI 194). At 1-month follow-up, the rate of death from any cause was 7.0% in patients treated with PPCI alone vs 3.0% in patients treated with TA + PPCI (p 0.036), whereas death from cardiovascular causes was 6.0% in the PPCI group vs 3.0% in the TA + PPCI group (p 0.028). Equally important, the rate of re-hospitalization due to heart failure was 7.5% in the PPCI group vs 4.0% in TA + PPCI group (p 0.025) and the rate of re-hospitalization due to acute coronary syndrome was 10.0% in the PPCI group vs 4.5% in the TA + PPCI group (p 0.016).

These results indicate the importance of TA in the treatment of STEMI in a group of high-risk patients such as elderly with frailty.

These results indicate the importance of TA in the treatment of STEMI in a group of high-risk patients such as elderly with frailty.Silversides are a widely distributed group across South America, with several species occupying marine, freshwater and estuarine environments. Several authors suggest main transitions among these environments took place during Pleistocene, and were accompanied with rapid speciation events. This scenario produced very limited genetic and morphological differentiation among the species. However, most of these surveys have an incomplete coverage of the intraspecific genetic diversity of the taxa studied. In this work, we reconstructed six mitochondrial genomes of O. argentinensis using transcriptomic data, and used them-in combination with several nuclear markers retrieved from the same transcriptomes-to explore the effect of additional coverage of intraspecific diversity of this species in phylogenetic reconstructions. Unlike previous works, phylogenetic analyses failed to identify O. argentinensis as a monophyletic group in relation with closely related taxa. Our results suggest that several species of the genus, especially those related to O. argentinensis, need further taxonomic revision.LSG is one of the most performed bariatric procedures worldwide. It is a safe and effective operation with a low complication rate. Unsatisfactory weight loss/regain may occur, suggesting that the operation design could be improved. A bioengineering approach might significantly help in avoiding the most common complications. Computational models of the sleeved stomach after LSG were developed according to bougie size (range 27-54 Fr). The endoluminal pressure and the basal volume were computed at different intragastric pressures. At an inner pressure of 22.5 mmHg, the basal volume of the 54 Fr configuration was approximately 6 times greater than that of the 27 Fr configuration (57.92 ml vs 9.70 ml). Moreover, the elongation distribution of the gastric wall was assessed to quantify the effect on mechanoreceptors impacting satiety by differencing regions and layers. An increasing trend in elongation strain with increasing bougie size was observed in all cases. The most stressed region and layer were the antrum (approximately 25% higher stress than that in the corpus at 37.5 mmHg) and mucosa layer (approximately 7% higher stress than that in the muscularis layer at 22.5 mmHg), respectively. In addition, the pressure-volume behaviors were reported. Computational models and bioengineering methods can help to quantitatively identify some critical aspects of the "design" of bariatric operations to plan interventions, and predict and increase the success rate. Moreover, computational tools can support the development of innovative bariatric procedures, potentially skipping invasive approaches.

The complexity of HIV care and its expanding clinical workforce has created a need for new distance learning models to deliver medical education. We conducted a narrative review to assess the acceptability and effectiveness of recent eHealth HIV education interventions supporting HIV healthcare providers.

Evidence from 24 articles revealed that synchronous (real time), asynchronous (any time), and hybrid (combination) models of eHealth education are feasible and acceptable. Only two interventions (one asynchronous, one hybrid) of 19 included in the review utilized a randomized controlled design. Some studies showed improvement in confidence and perceived quality of case management, but few studies were designed to demonstrate impact. Successful eHealth education interventions require a thorough understanding of the target community's capacity and needs. Both synchronous and asynchronous strategies appear acceptable and potentially effective, but more studies are needed to assess impact on knowledge and practices to determine the most effective delivery models.