Rare variants in SQSTM1 and VCP genes and risk of sporadic inclusion body myositis

Genetic factors have been suggested to be involved in the pathogenesis of sporadic inclusion body myositis (sIBM). SQSTM1 and VCP are two key genes associated with several neurodegenerative disorders but have yet to be thoroughly investigated in sIBM. A candidate gene analysis was conducted using whole-exome sequencing data from 181 sIBM patients, and whole-transcriptome expression analysis was performed in patients with genetic variants of interest. We identified six rare missense variants in the SQSTM1 and VCP in seven sIBM patients (4.0%). Two variants SQSTM1 p.G194R and the VCP p.R159C were significantly overrepresented in this sIBM cohort compared with controls. Five of these variants had been previously reported in patients with degenerative diseases. The mRNA levels of MHC genes were up-regulated, this elevation being more pronounced in SQSTM1 patient group. We report for the first time potentially pathogenic SQSTM1 variants and expand the spectrum of VCP variants in sIBM. These data suggests that defects in neurodegenerative pathways may confer genetic susceptibility to sIBM and reinforce the mechanistic overlap in these neurodegenerative disorders

SQSTM1 and VCP mutations in a series of 205 inclusion body myositis cases

Introduction: Clinico-pathologically overlapping inherited dis- orders indicate that genetic factors might be involved in sporadic inclusion body myositis (IBM) pathogenesis. Objectives: To identify genetic risk factors associated with IBM. Methods: Whole-exome sequencing was performed in 205 IBM patients. Muscle tissue was pathologically evaluated and whole- transcriptome expression profiles generated. Results: We identified eight rare missense mutations in the SQSTM1 and VCP genes in 10 IBM patients (5%). Five of the mutations had been previously reported in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) with Paget’s disease of bone (PDB); p62 staining was increased and MHC-I was up-regulated in the muscle tissue of these patients, Conclusions: Variants in SQSTM1 and VCP may constitute genetic susceptibility factors for IBM. The occurrence of mutations in SQSTM1 and VCP in IBM, ALS, FTD and PDB rein- forces the link between these disorders, pinpointing converging pathogenic pathways resulting in impaired autophagy-lysosome processing, causing dysregulation of protein homeostasis

Electrical pulse-induced electrochemical biosensor for hepatitis E virus detection

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Efficacy and safety of Bimagrumab in sporadic inclusion body myositis : long-term extension of RESILIENT

ObjectiveTo assess long-term (2 years) effects of bimagrumab in participants with sporadic inclusion body myositis (sIBM).MethodsParticipants (aged 36-85 years) who completed the core study (RESILIENT [Efficacy and Safety of Bimagrumab/BYM338 at 52 Weeks on Physical Function, Muscle Strength, Mobility in sIBM Patients]) were invited to join an extension study. Individuals continued on the same treatment as in the core study (10 mg/kg, 3 mg/kg, 1 mg/kg bimagrumab or matching placebo administered as IV infusions every 4 weeks). The co-primary outcome measures were 6-minute walk distance (6MWD) and safety.ResultsBetween November 2015 and February 2017, 211 participants entered double-blind placebo-controlled period of the extension study. Mean change in 6MWD from baseline was highly variable across treatment groups, but indicated progressive deterioration from weeks 24-104 in all treatment groups. Overall, 91.0% (n = 142) of participants in the pooled bimagrumab group and 89.1% (n = 49) in the placebo group had >= 1 treatment-emergent adverse event (AE). Falls were slightly higher in the bimagrumab 3 mg/kg group vs 10 mg/kg, 1 mg/kg, and placebo groups (69.2% [n = 36 of 52] vs 56.6% [n = 30 of 53], 58.8% [n = 30 of 51], and 61.8% [ n = 34 of 55], respectively). The most frequently reported AEs in the pooled bimagrumab group were diarrhea 14.7% (n = 23), involuntary muscle contractions 9.6% (n = 15), and rash 5.1% (n = 8). Incidence of serious AEs was comparable between the pooled bimagrumab and the placebo group (18.6% [n = 29] vs 14.5% [n = 8], respectively).ConclusionExtended treatment with bimagrumab up to 2 years produced a good safety profile and was well-tolerated, but did not provide clinical benefits in terms of improvement in mobility. The extension study was terminated early due to core study not meeting its primary endpoint.Classification of EvidenceThis study provides Class IV evidence that for patients with sIBM, long-term treatment with bimagrumab was safe, welltolerated, and did not provide meaningful functional benefit. The study is rated Class IV because of the open-label design of extension treatment period 2.Neurological Motor Disorder

Nanosensors based detection of foodborne pathogens

Contaminated food cause by pathogens is one of the main reasons incidences of human diseases cases all around the world. Typically, most foodborne contaminants caused by bacteria, parasites and virus that have a major economic impact. It is important to restrain them, thus early detection system is very crucial. Several methods have been explored for the detection and identification of these microorganisms in food samples. However, some of these methods are involves complicated sample pre-treatment, laborious, time-consuming and are not suitable for on-site applications. Therefore, it is very important to develop rapid, sensitive, selective and more approachable detection methods. Recently, biosensors have been explored as alternative approach method and considered as one of most rapid and on-site applicable methods. Advancements in nanotechnology have provided biosensor with novel architecture by using nanoscaled materials and structures for enhance the biosensing performance. This article highlights the significant progress of nanosensor based on electrochemical and optical, and other types of nanosensors with the focus on the foodborne pathogen detection