High resolution kinematic approach for quantifying impaired mobility of dystrophic zebrafish larvae.

Dystrophin-deficient zebrafish larvae are a small, genetically tractable vertebrate model of Duchenne muscular dystrophy well suited for early stage therapeutic development. However, current approaches for evaluating their impaired mobility, a physiologically relevant therapeutic target, are characterized by low resolution and high variability. To address this, we used high speed videography and deep learning-based markerless motion capture to develop linked-segment models of larval escape response (ER) swimming.

Dominant stop-loss HNRNPA1 variants in juvenile-onset myopathy.

Introduction/aims: Heterogeneous nuclear ribonucleoprotein A1 is involved in nucleic acid homeostatic functions. The encoding gene HNRNPA1 has been associated with several neuromuscular disorders including an amyotrophic lateral sclerosis-like phenotype, distal hereditary motor neuropathy, multisystem proteinopathy, and various myopathies. We report two unrelated individuals with monoallelic stop loss variants affecting the same codon of HNRNPA1.

Effects of HMGCR deficiency on skeletal muscle development.

Pathogenic variants in were recently linked to a limb-girdle muscular dystrophy (LGMD) phenotype. The protein product HMG CoA reductase (HMGCR) catalyzes a key component of the cholesterol synthesis pathway. The two other muscle diseases associated with HMGCR, statin-associated myopathy (SAM) and autoimmune anti-HMGCR myopathy, are not inherited in a Mendelian pattern.

Role of PKN1 in Retinal Cell Type Formation.

We recently identified PKN1 as a developmentally active gatekeeper of the transcription factor neuronal differentiation-2 (NeuroD2) in several brain areas. Since NeuroD2 plays an important role in amacrine cell (AC) and retinal ganglion cell (RGC) type formation, we aimed to study the expression of NeuroD2 in the postnatal retina of WT and animals, with a particular focus on these two cell types. We show that PKN1 is broadly expressed in the retina and that the gross retinal structure is not different between both genotypes.

Comparison of direct oral anticoagulants and warfarin in chronic limb-threatening ischemia.

Objective: The role of direct oral anticoagulants (DOACs) in chronic limb-threatening ischemia after revascularization is unknown. Current evidence-based guidelines do not provide clear guidance on the role of anticoagulation or the selection of anticoagulant. Current practice is highly varied and based on provider and patient preference.

Optimizing assays of zebrafish larvae swimming performance for drug discovery.

Introduction: Zebrafish larvae are one of the few vertebrates amenable to large-scale drug discovery screens. Larval swimming behavior is often used as an outcome variable and many fields of study have developed assays for evaluating swimming performance. An unintended consequence of this wide interest is that details related to assay methodology and interpretation become scattered across the literature.

Mendelian Disorders in an Interstitial Cystitis/Bladder Pain Syndrome Cohort.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder causing symptoms of urinary frequency, urgency, and bladder discomfort or pain. Although this condition affects a large population, little is known about its etiology. Genetic analyses of whole exome sequencing are performed on 109 individuals with IC/BPS.

Variants in DTNA cause a mild, dominantly inherited muscular dystrophy.

DTNA encodes α-dystrobrevin, a component of the macromolecular dystrophin-glycoprotein complex (DGC) that binds to dystrophin/utrophin and α-syntrophin. Mice lacking α-dystrobrevin have a muscular dystrophy phenotype, but variants in DTNA have not previously been associated with human skeletal muscle disease. We present 12 individuals from four unrelated families with two different monoallelic DTNA variants affecting the coiled-coil domain of α-dystrobrevin.

The impact of COVID-19 on the treatment of opioid use disorder in carceral facilities: a cross-sectional study.

While the COVID-19 pandemic disrupted healthcare delivery everywhere, persons with carceral system involvement and opioid use disorder (OUD) were disproportionately impacted and vulnerable to severe COVID-associated illness. Carceral settings and community treatment programs (CTPs) rapidly developed protocols to sustain healthcare delivery while reducing risk of COVID-19 transmission. This survey study assessed changes to OUD treatment, telemedicine use, and re-entry support services among carceral and CTPs participating in the National Institute on Drug Abuse (NIDA)-funded study, Long-Acting Buprenorphine vs.

Parents' Political Ideology Predicts How Their Children Punish.

From an early age, children are willing to pay a personal cost to punish others for violations that do not affect them directly. Various motivations underlie such "costly punishment": People may punish to enforce cooperative norms (amplifying punishment of in-groups) or to express anger at perpetrators (amplifying punishment of out-groups). Thus, group-related values and attitudes (e.

Erratum: Skeletal muscle-specific overexpression of miR-486 limits mammary tumor-induced skeletal muscle functional limitations.

[This corrects the article DOI: 10.1016/j.omtn.

Tandem duplication within the DMD gene in Labrador retrievers with a mild clinical phenotype.

A form of dystrophinopathy with mild or subclinical neuromuscular signs has been previously reported in a family of Labrador retrievers. Markedly and persistently elevated creatine kinase activity was first noted at 6 months of age. Skeletal muscle biopsies revealed a dystrophic phenotype, with dystrophin non-detectable on western blotting and immunohistochemical staining, and with increased utrophin expression.

Diagnostic capabilities of nanopore long-read sequencing in muscular dystrophy.

Many individuals with muscular dystrophies remain genetically undiagnosed despite clinical diagnostic testing, including exome sequencing. Some may harbor previously undetected structural variants (SVs) or cryptic splice sites. We enrolled 10 unrelated families: nine had muscular dystrophy but lacked complete genetic diagnoses and one had an asymptomatic DMD duplication.

Skeletal muscle-specific overexpression of miR-486 limits mammary tumor-induced skeletal muscle functional limitations.

miR-486 is a myogenic microRNA, and its reduced skeletal muscle expression is observed in muscular dystrophy. Transgenic overexpression of miR-486 using muscle creatine kinase promoter (MCK-miR-486) partially rescues muscular dystrophy phenotype. We had previously demonstrated reduced circulating and skeletal muscle miR-486 levels with accompanying skeletal muscle defects in mammary tumor models.

Chronic Alcohol Exposure Among People Living with HIV Is Associated with Innate Immune Activation and Alterations in Monocyte Phenotype and Plasma Cytokine Profile.

Despite advances in antiretroviral therapy, chronic immune activation continues to be observed among individuals with well-controlled HIV viral loads, and is associated with non-AIDS defining morbidities among people living with HIV. Alcohol use disorder impacts a significant proportion of individuals living with HIV, and alcohol exposure is known to damage the intestinal epithelium which may increase translocation of pathogens and their molecular products, driving systemic immune activation and dysregulation. The aim of this study was to determine if adults living with HIV with well-controlled viral loads, who also suffer from alcohol use disorder with and without hepatitis C virus co-infection (n=23), exhibit evidence of advanced systemic immune activation, intestinal damage, and microbial translocation, as compared to adults living with HIV who are not exposed to chronic alcohol or other substances of abuse (n=29).

HIV clinic-based extended-release naltrexone versus treatment as usual for people with HIV and opioid use disorder: a non-blinded, randomized non-inferiority trial.

Background And Aim: Opioid agonist medications for treatment of opioid use disorder (OUD) can improve human immunodeficiency virus (HIV) outcomes and reduce opioid use. We tested whether outpatient antagonist treatment with naltrexone could achieve similar results.

Design: Open-label, non-inferiority randomized trial.

Correlates of days of medication for opioid use disorder exposure among people living with HIV in Northern Vietnam.

Background: In Vietnam, access to medications for opioid use disorder (MOUD) for people living with HIV has rapidly expanded, but MOUD use over time remains low. We sought to assess factors associated with days of MOUD treatment exposure.

Methods: From 2015 to 2019, patients with OUD in six Northern Vietnamese HIV clinics were randomized to receive HIV clinic-based buprenorphine (BUP/NX) or referral for methadone maintenance therapy (MMT) and followed for 12 months.

Perspectives on extended-release naltrexone induction among patients living with HIV and opioid use disorder: a qualitative analysis.

Background: The CHOICES study randomized participants with HIV and opioid use disorder (OUD) to HIV clinic-based extended-release naltrexone (XR-NTX), which requires complete cessation of opioid use, versus treatment-as-usual (i.e., buprenorphine, methadone).

Use of methamphetamine and alcohol among people with opioid use disorder and HIV in Vietnam: a qualitative study.

Background: Heroin use continues to drive HIV transmission in Vietnam, but methamphetamine and alcohol use are growing rapidly and, as in other countries, polysubstance use is widespread. The objective of this study was to understand the interplay between heroin, methamphetamine, and alcohol use among people with opioid use disorder (OUD) and HIV in Vietnam.

Methods: We conducted 44 in-depth, face-to-face qualitative interviews with people with OUD and HIV who participated in the BRAVO trial of buprenorphine versus methadone in five Vietnam HIV clinics.

hnRNP L is essential for myogenic differentiation and modulates myotonic dystrophy pathologies.

Introduction: RNA-binding proteins (RBPs) play an important role in skeletal muscle development and disease by regulating RNA splicing. In myotonic dystrophy type 1 (DM1), the RBP MBNL1 (muscleblind-like) is sequestered by toxic CUG repeats, leading to missplicing of MBNL1 targets. Mounting evidence from the literature has implicated other factors in the pathogenesis of DM1.

POLRMT mutations impair mitochondrial transcription causing neurological disease.

While >300 disease-causing variants have been identified in the mitochondrial DNA (mtDNA) polymerase γ, no mitochondrial phenotypes have been associated with POLRMT, the RNA polymerase responsible for transcription of the mitochondrial genome. Here, we characterise the clinical and molecular nature of POLRMT variants in eight individuals from seven unrelated families. Patients present with global developmental delay, hypotonia, short stature, and speech/intellectual disability in childhood; one subject displayed an indolent progressive external ophthalmoplegia phenotype.

HIV clinic-based buprenorphine plus naloxone versus referral for methadone maintenance therapy for treatment of opioid use disorder in HIV clinics in Vietnam (BRAVO): an open-label, randomised, non-inferiority trial.

Background: UNAIDS recommends integrating methadone or buprenorphine treatment of opioid use disorder with HIV care to improve HIV outcomes, but buprenorphine adoption remains limited in many countries. We aimed to assess whether HIV clinic-based buprenorphine plus naloxone treatment for opioid use disorder was non-inferior to referral for methadone maintenance therapy in achieving HIV viral suppression in Vietnam.

Methods: In an open-label, non-inferiority trial (BRAVO), we randomly assigned people with HIV and opioid use disorder (1:1) by computer-generated random number sequence, in blocks of ten and stratified by site, to receive HIV clinic-based buprenorphine plus naloxone treatment or referral for methadone maintenance therapy in six HIV clinics in Vietnam.