An implantable system for opioid safety.

Naloxone can effectively rescue victims from opioid overdose, but less than 5% survive due to delayed or absent first responder intervention. Current overdose reversal systems face key limitations, including low user adherence, false positive detection, and slow antidote delivery. Here, we describe a subcutaneously implanted robotic first responder to overcome these challenges.

Carbohydrate supplementation maintains physical performance during short-term energy deficit despite reductions in exogenous glucose oxidation.

Exogenous glucose oxidation is reduced 55% during aerobic exercise after three days of complete starvation. Whether energy deficits more commonly experienced by athletes and military personnel similarly affect exogenous glucose oxidation and what impact this has on physical performance remains undetermined. This randomized, longitudinal parallel study aimed to assess the effects of varying magnitudes of energy deficit (DEF) on exogenous glucoseoxidation and physical performance compared to energy balance (BAL).

Rethinking the rise of early onset gastrointestinal cancers: a call to action.

Since the early 1990s, there has been a dramatic rise in gastrointestinal cancers diagnosed in patients under age 50 for reasons that remain poorly understood. The most significant change has been the increase in incidence rates of early-onset colorectal cancer, especially rates of left-sided colon and rectal cancers. Increases in gastric, pancreatic, and other gastrointestinal cancer diagnoses have further contributed to this trend.

Brain mechanical properties predict longitudinal cognitive change in aging and Alzheimer's disease.

Age-related cognitive decline is a complex phenomenon that is influenced by various neurobiological processes at the molecular, cellular, and tissue levels. The extent of this decline varies between individuals and the underlying determinants of these differences are not fully understood. Two of the most prominent signs of cognitive decline in aging are the deterioration of episodic memory, which is a hallmark of Alzheimer's disease (AD), and the nearly always accompanying atrophy of the medial temporal lobe.

Evaluation of Cereblon-Directing Warheads for the Development of Orally Bioavailable PROTACs.

PROTACs usually occupy physicochemical space outside the one defined by classical drug-like molecules, which often presents considerable challenges in their optimization and development for oral administration. We have previously reported phenyl glutarimide (PG)-based BET PROTAC SJ995973, with improved overall degradation and antiproliferative activities compared to its direct thalidomide-based analogue dBET1, but similarly poor pharmacokinetic profile. To further demonstrate the PG utility, we describe here optimization efforts that led to the discovery of an orally bioavailable BET-PROTAC SJ44236 (), and results of a comprehensive comparative study with analogues containing alternative CRBN-directing warheads.

Advanced Restriction Imaging and Reconstruction Technology for Prostate Magnetic Resonance Imaging (ART-Pro): A Study Protocol for a Multicenter, Multinational Trial Evaluating Biparametric Magnetic Resonance Imaging and Advanced, Quantitative Diffusion Magnetic Resonance Imaging for the Detection of Prostate Cancer.

Multiparametric magnetic resonance imaging (mpMRI) is strongly recommended by current clinical guidelines for improved detection of clinically significant prostate cancer (csPCa). However, the major limitations are the need for intravenous (IV) contrast and dependence on reader expertise. Efforts to address these issues include use of biparametric magnetic resonance imaging (bpMRI) and advanced, quantitative magnetic resonance imaging (MRI) techniques.

Lateral End-Range Movement Profile and Shot Effectiveness During Grand Slam Tennis Match-Play.

End-range movements are among the most demanding but least understood in the sport of tennis. Using male Hawk-Eye data from match-play during the 2021-2023 Australian Open tournaments, we evaluated the speed, deceleration, acceleration, and shot quality characteristics of these types of movement in men's Grand Slam tennis. Lateral end-range movements that incorporated a change of direction (CoD) were identified for analysis using k-means (end-range) and random forest (CoD) machine learning models.

Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma.

Circulating tumor DNA (ctDNA) detection can predict clinical risk in early-stage tumors. However, clinical applications are constrained by the sensitivity of clinically validated ctDNA detection approaches. NeXT Personal is a whole-genome-based, tumor-informed platform that has been analytically validated for ultrasensitive ctDNA detection at 1-3 ppm of ctDNA with 99.

Impact of workflow times on successful reperfusion after endovascular treatment in the late time window.

Background And Purpose: Successful and complete reperfusion should be the aim of every endovascular thrombectomy (EVT) procedure. However, the effect of time delays on successful reperfusion in late window stroke patients presenting 6-to-24 h from onset has not been investigated.

Materials And Methods: We pooled individual patient-level data from seven trials and registries for anterior circulation stroke patients treated with EVT between 6 and 24 h from onset.

Structural Dynamics of the Ubiquitin Specific Protease USP30 in Complex with a Cyanopyrrolidine-Containing Covalent Inhibitor.

Inhibition of the mitochondrial deubiquitinating (DUB) enzyme USP30 is neuroprotective and presents therapeutic opportunities for the treatment of idiopathic Parkinson's disease and mitophagy-related disorders. We integrated structural and quantitative proteomics with biochemical assays to decipher the mode of action of covalent USP30 inhibition by a small-molecule containing a cyanopyrrolidine reactive group, . The inhibitor demonstrated high potency and selectivity for endogenous USP30 in neuroblastoma cells.

Broadband Long Wavelength Light Promotes Myopic Eye Growth and Alters Retinal Responses to Light Offset in Chick.

Purpose: Prolonged exposure to broadband light with a short-wavelength (blue) or long-wavelength (orange/red) bias is known to impact eye growth and refraction, but the mechanisms underlying this response are unknown. Thus, the present study investigated the effects of broadband blue and orange lights with well-differentiated spectrums on refractive development and global flash electroretinography (gfERG) measures of retinal function in the chick myopia model.

Methods: Chicks were raised for 4 days with monocular negative lenses, or no lens, under blue, orange, or white light.

Pediatric Borderline Ovarian Tumors: A Retrospective Study of 15 Cases at a Single Institution.

Borderline ovarian tumors (BOTs) are rare in pediatric populations and typically follow an indolent clinical course with few reported recurrences. Consequently, guidelines for pediatric BOT management are minimal. We retrospectively examined the management of 15 adolescent patients who underwent BOT resection at our institution over 14 years, with a specific focus on recurrence.

A multimodal neural signature of face processing in autism within the fusiform gyrus.

Atypical face processing is commonly reported in autism. Its neural correlates have been explored extensively across single neuroimaging modalities within key regions of the face processing network, such as the fusiform gyrus (FFG). Nonetheless, it is poorly understood how variation in brain anatomy and function jointly impacts face processing and social functioning.

A standards-based application for improving platelet transfusion workflow.

Objective: Thrombocytopenia is a common complication of hematopoietic stem-cell transplantation (HSCT), though many patients will become immune refractory to platelet transfusions over time. We built and evaluated an electronic health record (EHR)-integrated, standards-based application that enables blood-bank clinicians to match platelet inventory with patients using data previously not available at the point-of-care, like human leukocyte antigen (HLA) data for donors and recipients.

Materials And Methods: The web-based application launches as an EHR-embedded application or as a standalone application.

Multimodality Imaging Evaluation of Diseases of the Pulmonic Valve and Right Ventricular Outflow Tract for the Adult Cardiologist.

Disorders of the pulmonic valve (PV) receive considerably less attention than other forms of valvular heart disease. Due to the dramatically improved survival of children with congenital heart disease over the last 5 decades, there has been a steady increase in the prevalence of adults with congenital heart disease, which necessitates that clinicians become familiar with the anatomy and the evaluation of right ventricular outflow tract and PV anomalies. A multimodality imaging approach using echocardiography, cardiac computed tomography, and magnetic resonance imaging is essential for a comprehensive evaluation of the anatomy and function of the right ventricular outflow tract, PV, and supravalvular region.

Use of design thinking to develop a benchmarking tool to assess documentation procedures in a hospital pharmacy aseptic compounding unit: a case study.

Objectives: This paper combines the concepts of design thinking and benchmarking in an aseptic manufacturing context. Design thinking is a problem-solving approach that aims to understand user needs, generate ideas, prototypes and test solutions. There are no published examples in the Irish healthcare setting.

Antimicrobial resistant Enterobacterales of clinical importance in mute swans.

Urban water environments, including canals, harbours and estuaries are susceptible to contamination with antimicrobials and drug-resistant bacteria through domestic and industrial wastewater discharges and storm water overflows. There is potential for wildlife using these waters to acquire and transmit drug-resistant bacteria and antimicrobial resistance genes (ARGs) of clinical importance. This study aimed to assess clinically important drug-resistant bacteria in urban waterfowl, particularly mute swans.

Drivers of forest productivity in two regions of the United States: Relative impacts of management and environmental variables.

Climate, environmental conditions, and management strategies are key factors affecting forest net ecosystem production (NEP). However, little is known about the relationship between management approaches and regional to continental-scale forest productivity. In this study, we utilized forests of the U.

Parent-Adolescent Communication, Self-Efficacy, and Self-Management of Type 1 Diabetes in Adolescents.

Purpose: The purpose of this study was to investigate adolescent perspectives of parent-adolescent communication, type 1 diabetes mellitus (T1DM)-specific family conflict, self-efficacy, and their relationship to adolescent self-management of T1DM.

Methods: A cross-sectional survey design was employed. Adolescents completed measures of parent-adolescent communication, T1DM-specific family conflict, self-efficacy, and self-management, which included activation and division of responsibility for management tasks.

Epistaxis Versus Nonepistaxis Bleeding in Anticoagulated Patients With Atrial Fibrillation: Results From the ENGAGE AF-TIMI 48 Trial.

Background: Epistaxis is common with antithrombotic therapy and is often troublesome to patients, yet its frequency, severity, and outcomes are poorly characterized.

Methods And Results: Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) randomized 21 105 patients with atrial fibrillation and CHADS2 risk score ≥2 to higher-dose edoxaban regimen (60 mg daily, dose-reduced to 30 mg), lower-dose edoxaban regimen (30 mg, dose reduced to 15 mg, daily), or warfarin. Bleeds were adjudicated using International Society on Thrombosis and Haemostasis criteria.

Chronic GIPR agonism results in pancreatic islet GIPR functional desensitisation.

Objectives: There is renewed interest in targeting the glucose-dependent insulinotropic polypeptide receptor (GIPR) for treatment of obesity and type 2 diabetes. G-protein coupled receptor desensitisation is suggested to reduce the long-term efficacy of glucagon-like-peptide 1 receptor (GLP-1R) agonists and may similarly affect the efficacy of GIPR agonists. We explored the extent of pancreatic GIPR functional desensitisation with sustained agonist exposure.

SAFETY, PHARMACOKINETICS, AND CLINICAL EFFICACY OF ADS051, A NEUTROPHIL MODULATOR, IN ULCERATIVE COLITIS: RESULTS OF A RANDOMIZED PHASE 1B TRIAL.

Objectives: Ulcerative colitis (UC) is characterized by colonic inflammation, with neutrophils playing a key role in UC activity, prognosis, and response to therapies. Current UC therapeutics can have significant side effects and limited efficacy. ADS051 is a novel, oral, gut-restricted small molecule that modulates neutrophil migration and activation without in vitro suppression of T-cell activation.

Cardiopulmonary Exercise Test Interpretation Across the Lifespan in Congenital Heart Disease: A Scientific Statement From the American Heart Association.

Survivorship from congenital heart disease has improved rapidly secondary to advances in surgical and medical management. Because these patients are living longer, treatment and disease surveillance targets have shifted toward enhancing quality of life and functional status. Cardiopulmonary exercise testing is a valuable tool for assessing functional capacity, evaluating cardiac and pulmonary pathology, and providing guidance on prognosis and interventional recommendations.