ALSUntangled #77: Psilocybin.

ALSUntangled reviews alternate and off-label treatments prompted by patient interest. Here, we review psilocybin, a chemical derived from mushrooms and belonging in the category of drugs known as psychedelics. Psilocybin has plausible mechanisms for slowing ALS progression because of its ability to cross the blood brain barrier and effect neurogenesis and inflammation.

Expert-based physical activity guidelines for metabolic and bariatric surgery patients: a systematic review of randomized controlled trials.

Patients undergoing metabolic and bariatric surgery (MBS) can improve outcomes through a physically active lifestyle. Despite ongoing research, clinical recommendations for physical activity (PA) are not fully developed. For this review, 39 articles representing 24 randomized clinical trials satisfied inclusion criteria.

Detecting white adipose tissue browning in mice with in vivo R* mapping at 9.4T MRI.

White adipose tissue (WAT) browning is considered a promising strategy to combat obesity and related metabolic diseases. Currently, fat-water fraction (FWF) has been used as a marker for the loss of lipids associated with WAT browning. However, FWF may not be sensitive to metabolic changes and cannot specifically reflect iron-regulated metabolism during browning.

The advancement of structure, bioactivity, mechanism, and synthesis of bufotalin.

Toad venom, a family of toxic yet pharmacologically valuable biotoxins, has long been utilized in traditional medicine and holds significant promise in modern drug development. Bufotalin, a prominent bufotoxin, has demonstrated potent cytotoxic properties through mechanisms such as apoptosis induction, cell cycle arrest, endoplasmic reticulum stress activation, and inhibition of metastasis by modulating key pathways including Akt, p53, and STAT3/EMT signaling-these multi-target mechanisms position bufotalin as a promising agent to combat multidrug resistance in cancer therapy. Additionally, advances in bufotalin synthesis, including chemical and biocatalytic methods, have streamlined production, with strategies such as C14-α-hydroxylation and novel coupling techniques enhancing yield and reducing environmental impact.

Hippo pathway activation causes multiple lipid derangements in a murine model of cardiomyopathy.

Metabolic reprogramming occurs in cardiomyopathy and heart failure contributing to progression of the disease. Activation of cardiac Hippo pathway signaling has been implicated in mediating mitochondrial dysfunction and metabolic reprogramming in cardiomyopathy, albeit influence of Hippo pathway on lipid profile is unclear. Using a dual-omics approach, we determined alterations of cardiac lipids in a mouse model of cardiomyopathy due to enhanced Hippo signaling and explored molecular mechanisms.

International prevalence patterns of low eGFR in adults aged 18-60 without traditional risk factors from a population-based cross-sectional disadvantaged populations eGFR epidemiology (DEGREE) study.

The disadvantaged populations eGFR (estimated glomerular filtration rate) epidemiology (DEGREE) study was designed to gain insight into the burden of chronic kidney disease (CKD) of undetermined cause (CKDu) using standard protocols to estimate the general-population prevalence of low eGFR internationally. Therefore, we estimated the age-standardized prevalence of eGFR under 60 ml/min per 1.73m in adults aged 18-60, excluding participants with commonly known causes of CKD; an ACR (albumin/creatinine ratio) over 300 mg/g or equivalent, or self-reported or measured (HT) hypertension or (DM) diabetes mellitus, stratified by sex and location.

KLHL24 associated cardiomyopathy: Gene function to clinical management.

Background: KLHL24 (Kelch-like protein 24) is a significant component of the ubiquitin-proteasome system (UPS), involved in regulating protein turnover through targeted ubiquitination and degradation. Germline mutations in KLHL24 gene have been known to cause Epidermolysis Bullosa Simplex characterized by skin fragility but has recently been found to cause Cardiomyopathy.

Main Body: Various cardiomyopathies, including hypertrophic cardiomyopathy and dilated cardiomyopathy, leading to abnormal protein degradation and affecting the stability and function of essential cardiac proteins which finally results into structural and functional abnormalities in cardiac muscle.

Novel Digital Anomalies, Hippocampal Atrophy, and Mutations Expand the Genotypic and Phenotypic Spectra of CNKSR2 in the Houge Type of X-Linked Syndromic Intellectual Development Disorder (MRXSHG).

The Houge type of X-linked syndromic intellectual developmental disorder (MRXSHG) encompasses a spectrum of neurodevelopmental disorders characterized by intellectual disability (ID), language/speech delay, attention issues, and epilepsy. These conditions arise from hemizygous or heterozygous deletions, along with point mutations, affecting CNKSR2, a gene located at Xp22.12.

Understanding the financial barriers to treatment among individuals with opioid use disorder: a focus group study.

Introduction: Despite the established effectiveness and relatively widespread availability of Medications for Opioid Use Disorder, individuals seeking treatment frequently encounter various structural and social barriers, including costs of treatment. This study aimed to understand the financial barriers that affect treatment continuation in individuals with opioid use disorder (OUD).

Methods: In this qualitative study, seven semi-structured in-depth focus group interviews were conducted among 28 participants in treatment for OUD.

The asymptomatic tuberculosis proportion among the elderly population: a systematic review and meta-analysis.

Background: The elderly population is a high-risk group for tuberculosis, and increasing evidence demonstrates a comparatively high proportion of asymptomatic tuberculosis in this group. This study aimed to determine the proportion of asymptomatic tuberculosis among patients with active tuberculosis through active case finding in the elderly population.

Materials And Methods: We searched for relevant articles published from the establishment of each database to December 31, 2023 in Web of Science, PubMed, VIP database, Chinese National Knowledge Infrastructure, and Wanfang database.

Guidelines for Seizure Prophylaxis in Patients Hospitalized with Nontraumatic Intracerebral Hemorrhage: A Clinical Practice Guideline for Health Care Professionals from the Neurocritical Care Society.

Background: There is practice heterogeneity in the use, type, and duration of prophylactic antiseizure medications (ASM) in patients hospitalized with acute nontraumatic intracerebral hemorrhage (ICH).

Methods: We conducted a systematic review and meta-analysis assessing ASM primary prophylaxis in adults hospitalized with acute nontraumatic ICH. The following population, intervention, comparison, and outcome (PICO) questions were assessed: (1) Should ASM versus no ASM be used in patients with acute ICH with no history of clinical or electrographic seizures? (2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT/fPHT) be preferentially used? and (3) If an ASM is used, should a long (> 7 days) versus short (≤ 7 days) duration of prophylaxis be used? The main outcomes assessed were early seizure (≤ 14 days), late seizures (> 14 days), adverse events, mortality, and functional and cognitive outcomes.

Insulin clearance at randomisation and in response to treatment in youth with type 2 diabetes: a secondary analysis of the TODAY randomised clinical trial.

Aims/hypothesis: Insulin resistance and compensatory hyperinsulinaemia are core features leading to beta cell failure in youth-onset type 2 diabetes. Insulin clearance (IC) is also a key regulator of insulin concentrations, but few data exist on IC in youth-onset type 2 diabetes. In a secondary analysis of our Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) randomised clinical trial, we investigated potential sex-, race-, ethnicity- and treatment-related differences in IC in youth-onset type 2 diabetes and aimed to identify metabolic phenotypes associated with IC at baseline and in response to metformin, metformin plus a lifestyle intervention, and metformin plus rosiglitazone.

Epigenomic Landscape of Human Cumulus Cells in Premature Ovarian Insufficiency Using Single-Base Resolution Methylome and Hydroxymethylome.

Premature ovarian insufficiency (POI) has recently been reported to be linked with epigenetic changes. Previous studies have focused on the regulation of individual genes associated with ovarian function through single-gene epigenetic variations; however, there is a deficiency in the comprehensive comprehension of the epigenetic profile for POI. Therefore, we conducted a multi-omics study integrating methylation, hydroxymethylation and transcriptome sequencing analyses in cumulus cells from women with POI and their matched controls.

Vagus nerve stimulation in treatment-resistant depression: A one-year, randomized, sham-controlled trial.

Background: Few treatments are available for individuals with marked treatment-resistant depression (TRD).

Objective: Evaluate the safety and effectiveness of FDA-approved adjunctive vagus nerve stimulation (VNS) in patients with marked TRD.

Methods: This 12-month, multicenter, double-blind, sham-controlled trial included 493 adults with marked treatment-resistant major depression who were randomized to active or no-stimulation sham VNS for 12 months.

The Society of Thoracic Surgeons Expert Consensus Statements on a Framework for a Standardized National Robotic Curriculum for Thoracic Surgery Trainees.

Objective: With robotic technology's rapid growth and integration, an urgent need to bridge the educational gap in thoracic surgical training has emerged. This document, a result of consensus among a group of experts in the practice and training of robotic surgery from the Society of Thoracic Surgeons (STS), aims to provide a framework for a standardized national robotic curriculum for thoracic surgery trainees.

Methods: The STS Task Force on Robotic Thoracic Surgery and Workforce on E-learning and Educational Innovation assembled an expert group with the input of the Thoracic Surgery Director's Association (TSDA).

The role of the psychedelic experience in psilocybin treatment for treatment-resistant depression.

Objective: To determine the relationships between psilocybin dose, psychedelic experiences, and therapeutic outcome in treatment-resistant depression.

Methods: For treatment-resistant depression, 233 participants received a single dose of 25, 10, or 1 mg of COMP360 psilocybin (a proprietary, pharmaceutical-grade synthesized psilocybin formulation, developed by the sponsor, Compass Pathfinder Ltd.) with psychological support.

Toluene is a cerebral artery constrictor acting via BK channels.

Acute intoxication by toluene usually follows intentional inhalation to achieve a "high", which may lead to repeated use due to toluene's reinforcing properties. In both acute and chronic intoxication brain function is primarily affected. Neuronal and glial elements participate in toluene's reinforcing properties and chronic toxicity, yet the targets underlying acute toxicity remain unknown.

A programmable arthritis-specific receptor for guided articular cartilage regenerative medicine.

Objective: Investigational cell therapies have been developed as disease-modifying agents for the treatment of osteoarthritis (OA), including those that inducibly respond to inflammatory factors driving OA progression. However, dysregulated inflammatory cascades do not specifically signify the presence of OA. Here, we deploy a synthetic receptor platform that regulates cell behaviors in an arthritis-specific fashion to confine transgene expression to sites of cartilage degeneration.

DDX39A resolves replication fork-associated RNA-DNA hybrids to balance fork protection and cleavage for genomic stability maintenance.

Safeguarding replication fork stability in transcriptionally active regions is crucial for precise DNA replication and mutation prevention. Here, we discover the pervasive existence of replication fork-associated RNA-DNA hybrids (RF-RDs) in transcriptionally active regions of human cells. These hybrids function as protective barriers, preventing DNA2-mediated nascent DNA degradation and replication fork collapse under replication stress.

Declining trends and regional variations of organophosphate ester contamination in indoor dust from mainland China: Insights from a filed study and meta-analysis.

This study investigated the presence of 20 organophosphate esters (OPEs) in indoor dust samples collected from the Chinese cities of Lanzhou, Xining, and Lhasa. The results demonstrate the ubiquitous presence of most OPEs in these three cities, with the highest concentrations of ΣOPEs found in Xining. We also summarized the occurrence of OPEs in indoor environments from 38 studies with 1875 samples collected across various regions of mainland China from 2012 to 2023.

Isolated Langerhans cell histiocytosis of the stomach in adults: An analysis of clinicopathologic characteristics and molecular genetics.

Isolated gastric Langerhans cell histiocytosis (LCH) occurs extremely rarely in adults. We characterized the clinicopathological and molecular genetics of this rare entity. We retrospectively analyzed the clinicopathologic and prognostic features of 3 patients with isolated gastric LCH during the past 10 years, with a review of an additional 20 patients from the literature.

Case report of antifungal drug-induced phlebitis in a patient with myelodysplastic syndrome.

Rationale: This article summarized the nursing experience of phlebitis caused by intravenous infusion of amphotericin B cholesterol sulfate complex in a patient with myelodysplastic syndrome.

Patient Concerns: A 59-year-old man with myelodysplastic syndrome complicated with fungal infection was treated with antifungal therapy.

Diagnoses: Patient with myelodysplastic syndrome was diagnosed with secondary phlebitis caused by liposomal amphotericin B.

Survival analysis of clear cell renal cell carcinoma based on radiomics and deep learning features from CT images.

Purpose: To create a nomogram for accurate prognosis of patients with clear cell renal cell carcinoma (ccRCC) based on computed tomography images.

Methods: Eight hundred twenty-two ccRCC patients with contrast-enhanced computed tomography images involved in this study were collected. A rectangular region of interest surrounding the tumor was used to extract quantitative radiomics and deep-learning features, which were filtered by Cox proportional hazard regression model and least absolute shrinkage and selection operator.