Xanomeline-Trospium for Adults with Schizophrenia Experiencing Acute Psychosis: A Systematic Review and Meta-analysis of Safety and Tolerability Outcomes.

The United States Food and Drug Administration approved the xanomeline-trospium combination in September 2024 for treating schizophrenia, based in part on three double-blind, randomized placebo-controlled trials in adults with schizophrenia experiencing acute psychosis. This random-effects model pairwise meta-analysis of those three trials found that xanomeline-trospium was comparable to placebo in terms of all-cause discontinuation, discontinuation rate due to adverse events, Simpson-Angus Scale score change, Barnes Akathisia Rating Scale score change, body weight change, body mass index change, blood pressure change, serum total cholesterol change, blood glucose change, QTc interval changes, and the incidence of headache, somnolence, insomnia, dizziness, akathisia, agitation, tachycardia, gastroesophageal reflux disease, diarrhea, increased weight, and decreased appetite. However, xanomeline-trospium was associated with a higher incidence of at least one adverse event, dry mouth, hypertension, nausea, vomiting, dyspepsia, and constipation, and increased serum triglyceride compared with placebo.

Latest clinical frontiers related to autism diagnostic strategies.

The diagnosis of autism is currently based on the developmental history, direct observation of behavior, and reported symptoms, supplemented by rating scales/interviews/structured observational evaluations-which is influenced by the clinician's knowledge and experience-with no established diagnostic biomarkers. A growing body of research has been conducted over the past decades to improve diagnostic accuracy. Here, we provide an overview of the current diagnostic assessment process as well as of recent and ongoing developments to support diagnosis in terms of genetic evaluation, telemedicine, digital technologies, use of machine learning/artificial intelligence, and research on candidate diagnostic biomarkers.

Gene and phenome-based analysis of the shared genetic architecture of eye diseases.

While many eye disorders are linked through defects in vascularization and optic nerve degeneration, genetic correlation studies have yielded variable results despite shared features. For example, glaucoma and myopia both share optic neuropathy as a feature, but genetic correlation studies demonstrated minimal overlap. By leveraging electronic health record (EHR) resources that contain genetic variables such as genetically predicted gene expression (GPGE), researchers have the potential to improve the identification of shared genetic drivers of disease by incorporating knowledge of shared features to identify disease-causing mechanisms.

Sequence variants in HECTD1 result in a variable neurodevelopmental disorder.

Dysregulation of genes encoding the homologous to E6AP C-terminus (HECT) E3 ubiquitin ligases has been linked to cancer and structural birth defects. One member of this family, the HECT-domain-containing protein 1 (HECTD1), mediates developmental pathways, including cell signaling, gene expression, and embryogenesis. Through GeneMatcher, we identified 14 unrelated individuals with 15 different variants in HECTD1 (10 missense, 3 frameshift, 1 nonsense, and 1 splicing variant) with neurodevelopmental disorders (NDDs), including autism, attention-deficit/hyperactivity disorder, and epilepsy.

Prenatal gene editing for neurodevelopmental diseases: Ethical considerations.

Neurodevelopmental diseases (NDDs) are notoriously difficult to treat because clinical symptoms stem from developmental processes that begin before birth. Prenatal gene editing could fill the treatment gap for NDDs by targeting and permanently correcting the genetic variants that underlie these pathogenic developmental processes. At the same time, there is a risk of unintended edits to the fetus or the pregnant person that could result in serious adverse consequences that are difficult, if not impossible, to undo.

A cis-regulatory element controls expression of histone deacetylase 9 to fine-tune inflammasome-dependent chronic inflammation in atherosclerosis.

Common genetic variants in a conserved cis-regulatory element (CRE) at histone deacetylase (HDAC)9 are a major risk factor for cardiovascular disease, including stroke and coronary artery disease. Given the consistency of this association and its proinflammatory properties, we examined the mechanisms whereby HDAC9 regulates vascular inflammation. HDAC9 bound and mediated deacetylation of NLRP3 in the NACHT and LRR domains leading to inflammasome activation and lytic cell death.

Redirecting glucose flux during in vitro expansion generates epigenetically and metabolically superior T cells for cancer immunotherapy.

Cellular therapies are living drugs whose efficacy depends on persistence and survival. Expansion of therapeutic T cells employs hypermetabolic culture conditions to promote T cell expansion. We show that typical in vitro expansion conditions generate metabolically and functionally impaired T cells more reliant on aerobic glycolysis than those expanding in vivo.

Projection-targeted photopharmacology reveals distinct anxiolytic roles for presynaptic mGluR2 in prefrontal- and insula-amygdala synapses.

Dissecting how membrane receptors regulate neural circuits is critical for deciphering principles of neuromodulation and mechanisms of drug action. Here, we use a battery of optical approaches to determine how presynaptic metabotropic glutamate receptor 2 (mGluR2) in the basolateral amygdala (BLA) controls anxiety-related behavior in mice. Using projection-specific photopharmacological activation, we find that mGluR2-mediated presynaptic inhibition of ventromedial prefrontal cortex (vmPFC)-BLA, but not posterior insular cortex (pIC)-BLA, connections produces a long-lasting decrease in spatial avoidance.

Extracellular volume expansion drives vertebrate axis elongation.

The vertebrate bauplan is primarily established via the formation of embryonic tissues in a head-to-tail progression. The mechanics of this elongation, which requires the presomitic mesoderm (PSM), remain poorly understood. Here, we find that avian PSM explants can elongate autonomously when physically confined in vitro, producing a pushing force promoting posterior elongation of the embryo.

Interpretable data-driven chemometric approach for predicting non-optically active water quality parameters using ultraviolet-visible-near infrared absorption spectroscopy and physical-chemical measurements.

Non-optically active water quality parameters (NAWQPs) are essential for surface water quality assessments, although automated monitoring methods are time-consuming, include labor-intensive chemical pretreatment, and pose challenges for high spatiotemporal resolution monitoring. Advancements in spectroscopic techniques and machine learning may address these issues. We integrated ultraviolet-visible-near infrared absorption spectroscopy with physical-chemical measurements to predict total nitrogen (TN), dissolved oxygen (DO), and total phosphorus (TP) in the Yangtze River Basin, China.

Phosphorus release under short-term submergence of pasture soils in critical source areas.

Critical source areas (CSAs) can act as a source of phosphorus (P) in surface waters by releasing soil P to porewater during frequent rainfall events. The extent of P release under short-term, frequent submergence has not been systematically studied in CSAs in New Zealand. A study was conducted to explore the potential of three contrasting dairy and sheep/beef farm soils (Recent, Pallic and Allophanic soils) to release P to porewater and pondwater under short-term and frequent submergence.

Utilizing Preoperative Rectus Sheath Blocks to Decrease Opioid Administration During Pediatric Umbilical Hernia Repair.

Introduction: Regional anesthetic blocks are an adjunct to decrease pediatric opioid utilization and improve perioperative pain control. We compared opioid use in patients who underwent umbilical hernia repair (UHR) with or without preoperative bilateral rectus sheath block (BRSB).

Methods: We conducted a single-center retrospective cohort study evaluating opioid use in patients <18 years who underwent an UHR.

Pediatric ECMO Outcomes in Children With Severe Infections: Does Infectious Source Matter?

Background: Although Extracorporeal Membrane Oxygenation (ECMO) utilization in pediatric patients with cardiopulmonary failure due to infection improves mortality, it is unclear whether the infectious etiology impacts outcomes. The aim of this study is to compare ECMO outcomes in children with sepsis and severe acute lung injury secondary to infections based on culture data.

Methods: A retrospective review was done of patients aged <18 with severe infections whose management included ECMO from 2013 to 2022 at a quaternary children's hospital.

Quantitative approaches to structural intersectionality research: Conceptual and methodologic considerations.

There has been a recent influx in the development of novel measures of structural forms of discrimination, including structural racism, xenophobia, sexism, heterosexism, and cisgenderism. These systems of power and oppression are inherently interdependent and mutually constitutive, yet a paucity of research has investigated their joint impacts; this gap is likely reflective of the limited guidance that exists regarding how to effectively combine multiple measures of structural discrimination to examine their joint impacts on population health and health inequities. In this commentary, we seek to redress this by describing conceptual and methodologic considerations for population health researchers interested in conducting quantitative structural intersectionality research - an intersectionality-informed research approach focused on examining how systems of power and oppression intersect to shape population health and health inequities.

Immigrant experiences of harm in sexual and reproductive healthcare in Spain.

The medical encounter represents a site where patients may be harmed, with intersecting vulnerabilities shaping the risk and nature of this harm. Sexual and reproductive healthcare is an important site for exploring this dynamic. Questions concerning how immigrant women experience sexual and reproductive healthcare abound, with researchers and practitioners calling for greater attention to a population whose experiences are underrepresented in existing literature.

Development of a predictive model for pediatric intranasal drug delivery with nasal sprays: Leveraging intersubject variability in anatomical dimensions, administration-related parameters, and airway patency.

In this study, we examined the correlation between anatomical dimensions, spray administration parameters, pressure drop across 40 pediatric nasal cavities, and in vitro posterior drug delivery (PDD) using Nasacort ALLERGY 24HR and FLONASE SENSIMIST nasal suspensions sprays, with different nozzle and actuation designs. The importance of each parameter and their interaction in the outcome (PDD) was evaluated. To do so, initially we measured anatomical and administration-related parameters, and the pressure drop of each cavity.

Impact of continuous positive airway pressure therapy on restless legs syndrome in patients with coexistent obstructive sleep apnea: A qualitative systematic review.

Introduction: Obstructive sleep apnea (OSA) is characterized by repetitive episodes of complete or partial upper airway collapse during sleep. Restless legs syndrome (RLS) is a sleep-related movement disorder characterized by an uncomfortable urge to move the legs, especially during inactivity and evenings. Both OSA and RLS are common with significant overlap: RLS is present in up to 36% of those with OSA.

Neurocognitive performance in obsessive-compulsive disorder before and after treatment with cognitive behavioral therapy.

Background: Cross-sectional studies have reported neurocognitive performance deficits in obsessive-compulsive disorder (OCD), particularly on tasks assessing response inhibition and proactive control over stimulus-driven behaviors (task control). However, it is not clear whether these deficits represent trait-like markers of OCD or are state-dependent.

Methods: This study examined performance on two neurocognitive tasks in OCD patients (N = 26) before and after cognitive behavioral therapy (CBT) and matched healthy controls (HCs, N = 19).

Granulosa cell function in domestic animals: A review on the in vitro effects of FSH, insulin and insulin-like growth factor 1.

Ovarian granulosa cells produce a variety of biologically active compounds in addition to steroid hormones that include numerous families of growth factors, cytokines and adipokines. Many of these function as endocrine, paracrine and autocrine hormones to regulate ovarian activity. The goal of this review is to provide an update on the evidence in domestic animals on how FSH, insulin and IGF1 regulate the function of granulosa cells with a focus on ovarian steroidogenesis and cell proliferation with comparisons across six domestic animals: pigs, cattle, horses, water buffalo, goats and sheep.

Tensor neural networks for high-dimensional Fokker-Planck equations.

We solve high-dimensional steady-state Fokker-Planck equations on the whole space by applying tensor neural networks. The tensor networks are a linear combination of tensor products of one-dimensional feedforward networks or a linear combination of several selected radial basis functions. The use of tensor feedforward networks allows us to efficiently exploit auto-differentiation (in physical variables) in major Python packages while using radial basis functions can fully avoid auto-differentiation, which is rather expensive in high dimensions.

The benefit of national clinical guidelines for open lower limb fractures in reducing healthcare burden: A length of inpatient stay cost-analysis.

Introduction: Severe open lower limb fractures are complex and costly injuries. Studies reporting the costs associated with these injuries, the economic impact of complications, and the clinical benefit of adherence to national guidelines have been previously reported. However, the economic benefits of national guidelines and their relationship with length of inpatient stay have not been described.

A comparison of virtual reality and verbal imaginal exposure for childhood anxiety disorders.

Virtual reality is a promising tool for improving efficacy of exposure therapy for childhood anxiety disorders (CADs), particularly for exposures that are challenging to orchestrate in vivo. The present study compared virtual reality exposure (VRE) to verbal imaginal exposure (IE) on anxiety elicited, homework completion, and preparation for subsequent exposures. Forty-five youth with CADs completed both types of exposure in session (order randomly assigned), practiced one form of exposure as homework (randomly assigned), and returned a week later to repeat both exposures (in randomized order), provide user feedback, and complete a related in vivo exposure.

Severe postoperative pancreatitis following treatment of peritoneal metastases.

Postoperative pancreatitis is an unusual complication of upper abdominal surgery that can result in severe morbidity and has been associated with postoperative death. It can be caused by trauma to the surface of the gland, injury to pancreatic ducts, vascular compromise, ductal obstruction within the pancreas parenchyma or because of duodenal stagnation. Our database of peritoneal surface malignancy patients was surveyed in a search for patients who manifested signs and symptoms of severe postoperative pancreatitis.