TMEM63 proteins function as monomeric high-threshold mechanosensitive ion channels.

OSCA/TMEM63s form mechanically activated (MA) ion channels in plants and animals, respectively. OSCAs and related TMEM16s and transmembrane channel-like (TMC) proteins form homodimers with two pores. Here, we uncover an unanticipated monomeric configuration of TMEM63 proteins.

Posterior capsule edema in adhesive capsulitis: comparison with established non-contrast MRI findings and multivariable analysis.

Objectives: To evaluate posterior glenohumeral capsule edema compared to other MRI findings in adhesive capsulitis (AC).

Methods: This study was approved by the local Institutional Review Board and it is HIPAA compliant. A retrospective search identified subjects who received fluoroscopically guided intra-articular corticosteroid injections for AC and had an MRI within 6 months prior to injection.

Snapshot: Choroid plexus brain barrier.

Located in each brain ventricle, choroid plexus (ChP) tissue forms a blood-CSF barrier and produces cerebrospinal fluid (CSF) and other supportive factors. Sheets of ChP epithelial cells enclose a vascularized stroma of mesenchymal, immune, and neuron/glia-like cells. Burgeoning ChP studies are revealing its complex set of functions across the lifespan.

Development of webcam-collected and artificial-intelligence-derived social and cognitive performance measures for neurodevelopmental genetic syndromes.

This study focused on the development and initial psychometric evaluation of a set of online, webcam-collected, and artificial intelligence-derived patient performance measures for neurodevelopmental genetic syndromes (NDGS). Initial testing and qualitative input was used to develop four stimulus paradigms capturing social and cognitive processes, including social attention, receptive vocabulary, processing speed, and single-word reading. The paradigms were administered to a sample of 375 participants, including 163 with NDGS, 56 with idiopathic neurodevelopmental disability (NDD), and 156 neurotypical controls.

Quantitative somatosensory testing of the abdomen: establishing initial reference values across developmental age and biological sex.

Abdominal pain is a common symptom of several debilitating conditions (eg, inflammatory bowel disease, irritable bowel syndrome, and endometriosis) and affects individuals throughout their lifespan. Quantitative sensory testing (QST) reference values exist for many body sites but not the abdomen. Using a QST battery adapted from the German Research Network on Neuropathic Pain, we collected QST data on the upper and lower abdomen in 181 pain-free participants, ages 12 to 50 years, to establish reference values by age and biological sex.

ICAM1 antibody drug conjugates exert potent antitumor activity in papillary and anaplastic thyroid carcinoma.

Treatment options for anaplastic thyroid cancer (ATC) and refractory papillary thyroid carcinoma (PTC) are limited and outcomes remain poor. In this study, we determined via bioinformatic expression analyses and immunohistochemistry staining that intercellular adhesion molecule-1(ICAM1) is an attractive target for ATC and PTC. We designed and engineered two ICAM1-directed antibody-drug conjugate (I1-MMAE and I1-DXd), both of which potently and selectively ablate multiple human ATC and PTC cell lines without affecting non-plastic cells .

Advancing Understanding of Inequities in Rare Disease Genomics.

Purpose: Advances in genomic research have facilitated rare disease diagnosis for thousands of individuals. Unfortunately, the benefits of advanced genetic diagnostic technology are not distributed equitably among the population, as has been seen in many other health care contexts. Quantifying and describing inequities in genetic diagnostic yield is inherently challenging due to barriers to both clinical and research genetic testing.

Biallelic MED27 variants lead to variable ponto-cerebello-lental degeneration with movement disorders.

MED27 is a subunit of the Mediator multiprotein complex, which is involved in transcriptional regulation. Biallelic MED27 variants have recently been suggested to be responsible for an autosomal recessive neurodevelopmental disorder with spasticity, cataracts and cerebellar hypoplasia. We further delineate the clinical phenotype of MED27-related disease by characterizing the clinical and radiological features of 57 affected individuals from 30 unrelated families with biallelic MED27 variants.

Inflammasomes as regulators of non-infectious disease.

Inflammasomes are cytoplasmic organelles that stimulate inflammation upon cellular detection of infectious or non-infectious stress. While much foundational work has focused on the infection-associated aspects of inflammasome activities, recent studies have highlighted the role of inflammasomes in non-infectious cellular and organismal functions. Herein, we discuss the evolution of inflammasome components and highlight characteristics that permit inflammasome regulation of physiologic processes.

Neuroendocrine Gene Expression Coupling of Interoceptive Bacterial Food Cues to Foraging Behavior of .

Animal internal state is modulated by nutrient intake, resulting in behavioral responses to changing food conditions. The neural mechanisms by which internal states are generated and maintained are not well understood. Here, we show that in the nematode , distinct cues from bacterial food - interoceptive signals from the ingestion of bacteria and gustatory molecules sensed from nearby bacteria - act antagonistically on the expression of the neuroendocrine TGF-beta ligand DAF-7 from the ASJ pair of sensory neurons to modulate foraging behavior.

Sustaining wakefulness: Brainstem connectivity in human consciousness.

Consciousness is comprised of arousal (i.e., wakefulness) and awareness.

Rethinking mental healthcare for refugees.

After several years of downturn in new resettlement, the United States is projected to admit 125,000 refugees in the current fiscal year. Refugee communities have known risks of developing mental health problems due to high rates of exposure to war and conflict-related trauma and chronic stressors associated with displacement and resettlement. In this commentary, we examine limitations in the current system of mental health care available to newly arriving refugee communities and make recommendations for expanding and redesigning services to better meet the needs of culturally diverse refugee communities.

Predictors of Outcomes in 900 Alveolar Bone Grafts.

Background: Significant discrepancies exist in the reported variables influencing alveolar bone graft outcomes. The purpose of this study was to evaluate graft success and identify outcome predictors in a large patient cohort using an objective cone beam computed tomography assessment tool.

Methods: Consecutive patients with cleft lip/palate who underwent alveolar bone grafting by 1 surgeon were included.

Air Displacement Plethysmography is an Accurate and Feasible Noninvasive Measure of Fat-Free Mass in Children With Intestinal Failure.

Background: The nutritional status of children with intestinal failure (IF) can be difficult to determine using body weight and currently available anthropometric techniques. Air displacement plethysmography (ADP) is a noninvasive measure of whole-body composition that measures body mass and volume, with a calculation of percent body fat (%BF) and fat-free mass (FFM) that may be useful during the provision of specialized nutrition.

Objectives: To evaluate the validity and feasibility of measuring body composition in children with IF using ADP compared with deuterium dilution (DD), as well as secondarily with other measures of body composition, namely bioelectrical impedance analysis (BIA), dual-energy X-ray absorptiometry (DXA), and four-site skinfold anthropometry.

Researching models of innovation and adoption in health professions education.

Background: Despite the constant presence of change and innovation in health professions education (HPE), there has been relatively little theoretical modelling of such change, the experiences of change, the ideology associated with change or the unexpected consequences of change. In this paper, the authors explore theoretical approaches to the adoption of innovations in HPE as a way of mapping a broader theoretical landscape of change.

Method: The authors, HPE researchers with an interest in technology adoption and systemic change, present a narrative review of the literature based on a series of thought experiments regarding how communities and individuals respond to the introduction of new ideas or methods.

Multi-Task Training with In-Domain Language Models for Diagnostic Reasoning.

Generative artificial intelligence (AI) is a promising direction for augmenting clinical diagnostic decision support and reducing diagnostic errors, a leading contributor to medical errors. To further the development of clinical AI systems, the Diagnostic Reasoning Benchmark (DR.BENCH) was introduced as a comprehensive generative AI framework, comprised of six tasks representing key components in clinical reasoning.

The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).

Objective: Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most inflammatory contexts. They can progress rapidly, and early identification and management are critical for preventing organ failure and mortality. This effort aimed to develop evidence-based and consensus-based points to consider to assist clinicians in optimising decision-making in the of diagnosis, treatment and monitoring of HLH/MAS.

The 2022 EULAR/ACR Points to Consider at the Early Stages of Diagnosis and Management of Suspected Haemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS).

Objective: Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most inflammatory contexts. They can progress rapidly, and early identification and management are critical for preventing organ failure and mortality. This effort aimed to develop evidence-based and consensus-based points to consider to assist clinicians in optimising decision-making in the early stages of diagnosis, treatment and monitoring of HLH/MAS.

Pancreatitis-Associated Medication Use in Hospitalized Pediatric and Young Adult Patients With Acute Pancreatitis.

Objective: The objective of this study is (1) to describe the prevalence of pancreatitis-associated medication (PAM) use at admission and discharge in pediatric and young adult patients hospitalized with acute pancreatitis (AP) and (2) to describe the prevalence of PAM use at admission in patients classified as having idiopathic AP.

Study Design: A single-center retrospective study of patients <21 years who were hospitalized with AP or acute recurrent pancreatitis from March 2015 to July 2017 was performed. Charts were reviewed for demographic data, etiology of pancreatitis, comorbidities, and use of PAMs at admission and discharge.

Evolution of clinical and translational advances in the management of pediatric arteriovenous malformations.

Arteriovenous malformations (AVMs) represent one of the most challenging diagnoses in pediatric neurosurgery. Until recently, the majority of AVMs was only identified after hemorrhage and primarily treated with surgery. However, recent advances in a wide range of fields-imaging, surgery, interventional radiology, radiation therapy, and molecular biology-have profoundly advanced the understanding and therapy of these complex lesions.

Tranexamic Acid Use in Pediatric Craniotomies at a Large Tertiary Care Pediatric Hospital: A Five Year Retrospective Study.

Tranexamic acid (TXA), a synthetic antifibrinolytic drug, has proven efficacy and is recommended for major pediatric surgery to decrease perioperative blood loss. Accumulating evidence suggests that TXA reduces bleeding and transfusion in a variety of adult neurosurgical settings. However, there is a paucity of research regarding TXA indications for pediatric neurosurgery and thus, there are currently no recommendations for its use with this specific population.

Is chronotype linked with adherence to the Mediterranean diet among adolescents? The EHDLA study.

Background: No previous study has evaluated the relationship between chronotype and adherence to the Mediterranean diet among adolescents. The aim of the present study was to assess the association between chronotype and adherence to the Mediterranean diet in a sample of Spanish adolescents aged 12-17 years.

Methods: This study examined secondary data from 820 adolescents (55.