elimination disorders

BACKGROUND: Once-nightly sodium oxybate (ON-SXB), an extended-release oxybate formulation, yielded significant ( P  < 0.001 at 6 g, 7.5 g, and 9 g) reductions in cataplexy episodes in participants in the phase 3 REST-ON clinical trial (NCT02720744). This post hoc analysis from REST-ON further characterized changes in cataplexy episodes in participants with narcolepsy type 1 (NT1). METHODS: Participants with narcolepsy aged ≥16 years received ON-SXB (1 wk, 4...

BACKGROUND: The COVID-19 pandemic catalyzed a rapid shift in healthcare delivery towards telehealth services, impacting patient care, including opioid use disorder (OUD) treatment. Regulatory changes eliminated the in-person evaluation requirement for buprenorphine treatment, encouraging adoption of telehealth. This study focused on understanding experiences of primary care providers in predominantly rural areas who used telehealth for OUD treatment during the pandemic. METHODS: Semi-structured interviews were conducted with 22 primary care providers...

DNA-protein crosslinks (DPCs) induced by aldehydes interfere with replication and transcription. Hereditary deficiencies in DPC repair and aldehyde clearance processes cause progeria, including Ruijs-Aalfs syndrome (RJALS) and AMeD syndrome (AMeDS) in humans. Although the elimination of DPC during replication has been well established, how cells overcome DPC lesions in transcription remains elusive. Here we show that endogenous aldehyde-induced DPC roadblocks are efficiently resolved by transcription-coupled repair (TCR)...

Regulation of nicotine vaping products (NVPs) is an ongoing challenge across the world. Australia currently has a globally unique NVP regulatory model that requires a medical prescription to purchase and use NVPs, with further restrictions in progress in response to evidence of widespread illicit NVP sales. Against this background, we examine the new measures and consider a modification of the model to pharmacist-only supply as an option for increasing access to NVPs for smoking cessation, while retaining health practitioner oversight of supply...

Major Depressive Disorder (MDD) is a widespread psychiatric condition that affects a significant portion of the global population. The classification and diagnosis of MDD is crucial for effective treatment. Traditional methods, based on clinical assessment, are subjective and rely on healthcare professionals' expertise. Recently, there's growing interest in using Resting-State Functional Magnetic Resonance Imaging (rs-fMRI) to objectively understand MDD's neurobiology, complementing traditional diagnostics...

Sirtuin1 (SIRT1), an NAD+ -dependent histone deacetylase, plays a crucial role in regulating molecular signaling pathways. Recently, inhibition of SIRT1 rather than its activation shows the therapeutic potential for central nervous system disorder, however, the discovered SIRT1 inhibitors remains limited. In this work, a dual recognition-based strategy was developed to screen SIRT1 inhibitors from natural resources in situ. This approach utilized a Ni-modified metal-organic framework (Ni@Tyr@UiO-66-NH2 ) along with cell lysate containing an engineered His-tagged SIRT1 protein, eliminating the need for purified proteins, pure compounds, and protein immobilization...

INTRODUCTION: After a promising start in Australia, elimination efforts for hepatitis C are not on track. Following the global campaign to 'find the missing' in hepatitis C response, this qualitative study explores stakeholder perspectives on the 'missing' in the 'endgame' of hepatitis elimination in the state of New South Wales, Australia. METHOD: Twenty-eight key informants working in New South Wales, elsewhere in Australia and internationally in high income countries participated in a semi-structured qualitative interview...

BACKGROUND: Recurrent upper endoscopies are essential for monitoring therapy response and disease activity in patients with eosinophilic esophagitis (EoE), leading to increased costs, procedural complications, and anesthesia exposure. The aim of this study was to examine an office-based model using serial sedation-free blind esophageal epithelial brushing (BEEB) to monitor therapy response through eosinophil-derived neurotoxin (EDN) levels and guide therapy plans in pediatric EoE patients...

BACKGROUND: Discontinuing sublingual buprenorphine (SL-BUP) has been identified by some patients as a potential outcome of success for opioid use disorder treatment. The process of tapering SL-BUP can be lengthy as unpleasant opioid withdrawal symptoms limit the pace of dose adjustments. Uncontrolled withdrawal symptoms pose a risk for return to illicit opioid use and more patient-centered options for tapering SL-BUP are needed. Previous case reports have identified using extended-release subcutaneous buprenorphine (ER-BUP) to minimize withdrawal symptoms as the dose self-decreases very gradually...

BACKGROUND: Autoimmune diseases encompass a diverse array of disorders that disturb the optimal functioning of the immune system, which is to eliminate the 'foreign or/and dangerous' to mistakenly target the body's own tissues. OBJECTIVE: The aim of this research is to evaluate the most effective approach to managing autoimmune diseases within the framework of pregnancy. METHODS: The exact causes and etiologies of these diseases are multifactorial and mostly still unclear...

Protein misfolding, aggregation, and spread through the brain are primary drivers of neurodegenerative diseases pathogenesis. Phagocytic glia are responsible for regulating the load of pathogenic protein aggregates in the brain, but emerging evidence suggests that glia may also act as vectors for aggregate spread. Accumulation of protein aggregates could compromise the ability of glia to eliminate toxic materials from the brain by disrupting efficient degradation in the phagolysosomal system. A better understanding of phagocytic glial cell deficiencies in the disease state could help to identify novel therapeutic targets for multiple neurological disorders...

Cough is a common symptom of multiple respiratory diseases, such as asthma and chronic obstructive pulmonary disorder. Various research works targeted cough detection as a means for continuous monitoring of these respiratory health conditions. This has been mainly achieved using sophisticated machine learning or deep learning algorithms fed with audio recordings. In this work, we explore the use of an alternative detection method, since audio can generate privacy and security concerns related to the use of always-on microphones...

BACKGROUND: The elimination of restrictive practices, such as seclusion and restraint, is a major aim of mental health services globally. The role of art therapy, a predominantly non-verbal mode of creative expression, is under-explored in this context. This research aimed to determine whether art therapy service provision was associated with a reduction in restrictive practices on an acute inpatient child and adolescent mental health services (CAMHS) unit. METHODS: The rate (events per 1,000 occupied bed days), frequency (percent of admitted care episodes with incident), duration, and number of incidents of restrictive practices occurring between July 2015 and December 2021 were analysed relative to art therapy service provision...

PURPOSE: This study examined time trends in significant child and adolescent psychological symptoms and explored the association of frequent and problematic social media use with these symptoms. METHODS: Time trends in psychological symptoms were assessed using data from five waves of the international survey of Health Behavior in School-aged Children (HBSC), conducted between 2001 and 2018 (N = 1,036,869). The associations of frequent and problematic social media use with significant psychological symptoms were assessed by hierarchical multinomial logistic regression using data from 2001-2002 and the 2017-2018 survey waves...

Vestibular rehabilitation therapy (VRT) is a highly effective treatment approach for addressing both peripheral and central vestibular disorders, offering the ability to significantly improve patients' coordination and control across the vestibular, visual, and proprioceptive systems, all of which are crucial factors in maintaining balance. By promoting vestibular compensation, VRT has been shown to mitigate or even eliminate symptoms of dizziness, vertigo, and instability. With the rapid development of vestibular research, VRT has evolved into a more individualized and precise treatment approach based on evidence-based medicine...

Signal transduction through G protein-coupled receptors (GPCRs) has been a major focus in cell biology for decades. Numerous disorders are associated with GPCRs that utilize Gi proteins to inhibit adenylyl cyclase (AC) as well as regulate other effectors. Several early studies have successfully defined the AC-interacting domains of several members of Gαi by measuring the loss of activity upon homologous replacements of putative regions of constitutive active Gαi mutants. However, whether such findings can indeed be translated into the context of a receptor-activated Gαi have not been rigorously verified...

OBJECTIVE: Tolvaptan is a vasopressin V2 receptor antagonist that is commonly prescribed to alleviate edema associated with renal diseases. However, the clinical benefits of tolvaptan in chronic kidney disease (CKD) remain unclear. This study aimed to evaluate the effectiveness of tolvaptan in managing edema caused by CKD. MATERIALS AND METHODS: The efficacy and treatment regimen of tolvaptan were assessed in a cohort of 96 patients with renal edema and CKD. During the treatment, the patients' creatinine (CR), uric acid (UA), and estimated glomerular filtration rate (eGFR) were monitored as important indicators of kidney function...

BACKGROUND: Hepatitis C virus (HCV) is a major health threat in Canada. In British Columbia (BC) province, 1.6% of the population had been exposed to HCV by 2012. Prevalence and incidence of HCV are very high in populations of people who use drugs (PWUD) and sex workers (SW), who may experience unique barriers to healthcare. Consequently, they are less likely to be treated for HCV. Overcoming these barriers is critical for HCV elimination. This research sought to explore the healthcare experiences of PWUD and SW and how these experiences impact their willingness to engage in healthcare in the future, including HCV care...

Epilepsy is a neurological disorder characterized by overstimulation of neurotransmitters and uncontrolled seizures. Current medications for epilepsy result in adverse effects or insufficient seizure control, highlighting the necessity to develop alternative therapies. Cannabidiol (CBD), derived from cannabis plants, has been popularly explored as an alternative. CBD is shown to have anti-convulsivatng and muscle-relaxing properties, which have been used in patients with epilepsy with promising results. Current research explores varying dosages in either adult or paediatric patients, with little or no comparison between the two populations...

Mitochondrial DNA (mtDNA) analysis is crucial for the diagnosis of mitochondrial disorders, forensic investigations, and basic research. Existing pipelines are complex, expensive, and require specialized personnel. In many cases, including the diagnosis of detrimental single nucleotide variants (SNVs), mtDNA analysis is still carried out using Sanger sequencing. Here, we developed a simple workflow and a publicly available webserver named Mitopore that allows the detection of mtDNA SNVs, indels, and haplogroups...