Japanese encephalitis virus is absolutely dependent on their host cells and has evolved various strategies to manipulate the cellular secretory pathways for viral replication. However, how cellular secretory pathways are hijacked, and the origin of the viral vesicles remains elusive during JEV replication. Here we show how JEV manipulates multiple components of the cellular secretory pathway, including autophagic machinery, to generate a superior environment for genome replication. We utilized double-strand RNA antibodies to label JEV RNA complex seeking the viral replication compartments and found that JEV genome replication takes place in lysosomes (LAMP1), not in autophagosomes (LC3). Subsequently, in situ hybridization results showed that viral RNAs (vRNAs) of JEV strongly colocalized with LAMP1. What surprised us was that JEV vRNAs markedly colocalized with LC3, indicating that autophagy plays an active role in JEV replication. Interestingly, we found that JEV utilized autophagic components for intracellular growth in an autophagy-dependent manner and the fusion of autophagosome-lysosome plays a positive role in JEV post-RNA replication processes. Collectively, our findings demonstrate that JEV can manipulate cellular secretory pathway to form genome replication organelles and exploit autophagy components for intracellular growth, providing new insights into the life cycle of JEV and uncovering an attractive target for antiviral drugs.
  The Motor Neuron Disease Behavioural Scale (MiND-B) is a clinically validated tool that was developed to detect behavioural dysfunction in patients with amyotrophic lateral sclerosis (ALS). The current study aimed to evaluate behavioural impairment using MiND-B, as well as cognitive dysfunction in ALS patients, and to determine their prognostic implications.
 
  Patients with a clinical diagnosis of ALS were prospectively recruited from a specialised multidisciplinary ALS clinic. Patients underwent behavioural assessment with the Motor Neuron Disease Behavioural Scale (MiND-B) and cognitive evaluation using the Addenbrooke's Cognitive Examination (ACE). Primary outcome measure was selected as survival time, defined by time from assessment to time of death or censor date. Univariate assessment of survival effect was carried out using Kaplan-Meier survival analysis followed by cox regression analysis to assess the effect of MiND-B and ACE scores on survival time.
 
  A total of 134 patients were included in the s simple and efficient clinical tools that can be administered in the multidisciplinary ALS clinic, that aid in the prognostication of this patient population.
  Research output is one element of a multifactorial process that residency programs consider when evaluating applicants. However, there are minimal data assessing research productivity on admittance into research-oriented integrated vascular surgery residency (RO-IVSR) programs. The purpose of this study was to evaluate the association of peer-reviewed research and the RO-IVSR match process.
 
  Vascular surgery residents who matched into an RO-IVSR in 2015-2017 were divided into those matching an RO-IVSR top 10 program versus other. Total publications, first authorships, and type of research were compared between groups. Mann-Whitney U-tests were then performed between discrete levels of research productivity (0-1 versus ≥2 publications) to detect differences in ability to match a top 10 program.
 
  One hundred and fifty-eight residents published a total of 214 original research articles (83%), 26 case reports (10%), and 19 systematic reviews (7%). There were 66 first authorships (25%). Median total publicatio an applicants' research productivity as a distinct qualification category and a marker of future success.Mutations in nuclear genes encoding for mitochondrial proteins very long-chain acyl-CoA dehydrogenase (VLCAD) and trifunctional protein (TFP) cause rare autosomal recessive disorders. Studies in fibroblasts derived from patients with mutations in VLCAD and TFP exhibit mitochondrial defects. To gain insights on pathological changes that account for the mitochondrial deficits we performed quantitative proteomic, biochemical, and morphometric analyses in fibroblasts derived from subjects with three different VLCAD and three different TFP mutations. Proteomic data that was corroborated by antibody-based detection, indicated reduced levels of VLCAD and TFP protein in cells with VLCAD and TFP mutations respectively, which in part accounted for the diminished fatty acid oxidation capacity. Decreased mitochondrial respiratory capacity in cells with VLCAD and TFP mutations was quantified after glucose removal and cells with TFP mutations had lower levels of glycogen. Despite these energetic deficiencies, the cells with VLCAD and TFP mutations did not exhibit changes in mitochondria morphology, distribution, fusion and fission, quantified by either confocal or transmission electron microscopy and corroborated by proteomic and antibody-based protein analysis. Fibroblasts with VLCAD and to a lesser extend cells with TFP mutations had increased levels of mitochondrial respiratory chain proteins and proteins that facilitate the assembly of respiratory complexes. With the exception of reduced levels of catalase and glutathione S-transferase theta-1 in cells with TFP mutations, the levels of 45 proteins across all major intracellular antioxidant networks were similar between cells with VLCAD and TFP mutations and non-disease controls. Collectively the data indicate that despite the metabolic deficits, cells with VLCAD and TFP mutations maintain their proteomic integrity to preserve cellular and mitochondria architecture, support energy production and protect against oxidative stress.In this meta-analysis we updated a review from 2013 investigating the evidence on the efficacy of hypnosis in adults undergoing surgical procedures compared to standard care alone or an attention control. A comprehensive literature search using Medline, CENTRAL, Web of Science, PsycINFO, ProQuest Dissertations and Theses database, and manual searches were conducted to identify randomized controlled trials. In this update, N = 23 eligible studies were added to the existing study pool, resulting in N = 50 studies with 4269 patients. Random effects meta-analyses revealed positive treatment effects on mental distress (g = 0.55, 95% CI [0.39; 0.70], NNT = 3.32), pain (g = 0.37, 95% CI [0.25; 0.50], NNT = 4.78), medication consumption (g = 0.46, 95% CI [0.23; 0.68], NNT = 3.95), recovery (g = 0.26, 95% CI [0.09; 0.42], NNT = 6.91), and surgical procedure time (g = 0.23, 95% CI [0.14; 0.33], NNT = 7.6). No effects were found for physiological parameters (g = 0.13, 95% CI [-0.06; 0.33], NNT = 13.26).  https://www.selleckchem.com/products/rocaglamide.html  95% prediction intervals included the null effect for all outcomes except for procedure time.