A Drosophila cardiac myosin increases jump muscle stretch activation and shortening deactivation.

Stretch activation (SA), a delayed increase in force production following rapid muscle lengthening, is critical to the function of vertebrate cardiac muscle and insect asynchronous indirect flight muscle (IFM). SA enables or increases power generation in muscle types used in a cyclical manner. Recently, myosin isoform expression has been implicated as a mechanism for varying the amplitude of SA in some muscle types.

Intersection of rare pathogenic variants from TCGA in the All of Us Research Program v6.

Using rare cancer predisposition alleles derived from The Cancer Genome Atlas (TCGA) and high cancer prevalence (14% of participants) in All of Us (version 6), we assessed the impact of these rare alleles on cancer occurrence in six broad groups of genetic similarity provided by All of Us: African/African American (AFR), Admixed American/Latino (AMR), East Asian (EAS), European (EUR), Middle Eastern (MID), or South Asian (SAS). We observed that germline susceptibility to cancer consistently replicates in EUR-like participants but less so in other participants. We found that All of Us participants from the EUR (p = 1.

Characterization of a novel conditional knockout mouse model to assess efficacy of mRNA therapy in the context of severe ornithine transcarbamylase deficiency.

Ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle disorder, characterized by hyperammonemia and accompanied by a high unmet patient need. mRNA therapies have been shown to be efficacious in hypomorphic Sparse-fur abnormal skin and hair (Spf-ash) mice, a model of late-onset disease. However, studying the efficacy of ornithine transcarbamylase (OTC) mRNA therapy in traditional knockout mice, a model for severe early-onset OTCD, is hampered by the rapid lethality of the model, and poor lipid nanoparticle (LNP) uptake into neonatal mouse liver.

Efficient Gene Delivery Admitted by small Metabolites Specifically Targeting Astrocytes in the Mouse Brain.

The development of efficient and targeted methods for delivering DNA in vivo has long been a major focus of research. In this study, we introduce a gene Delivery approach Admitted by small Metabolites, named gDAM, for the efficient and targeted delivery of naked DNA into astrocytes in the adult brains of mice. gDAM utilizes a straightforward combination of DNA and small metabolites, including glycine, L-proline, L-serine, L-histidine, D-alanine, Gly-Gly, and Gly-Gly-Gly, to achieve astrocyte-specific delivery of naked DNA, resulting in transient and robust gene expression in these cells.

Artificial enforcement of the unfolded protein response (UPR) reduces disease features in multiple preclinical models of ALS/FTD.

Amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD) are part of a spectrum of diseases that share several causative genes, resulting in a combinatory of motor and cognitive symptoms and abnormal protein aggregation. Multiple unbiased studies have revealed that proteostasis impairment at the level of the endoplasmic reticulum (ER) is a transversal pathogenic feature of ALS/FTD. The transcription factor XBP1s is a master regulator of the unfolded protein response (UPR), the main adaptive pathway to cope with ER stress.

Psychotic-Spectrum Disorders With Comorbid Anxiety are Predisposing Factors for Parkinson's Disease in a Case-Control Study.

Background: Multiple studies have demonstrated associations between psychiatric conditions and Parkinson's disease (PD) development; fewer have examined psychotic-spectrum disorders and PD development.

Objective: The objective was to assess the prevalence of psychotic-spectrum disorders with and without depression and anxiety preceding a PD diagnosis.

Methods: In this retrospective, case-control study of adults > 60 years of age, cases were identified by PD diagnosis and controls were identified in a 3:1 ratio by ambulatory encounter from 2015 to 2020.

Comparative diversification analyses of Hydrangeaceae and Loasaceae reveal complex evolutionary history as species disperse out of Mesoamerica.

Premise: The movement of lineages into novel areas can promote ecological opportunity and adaptive radiation, leading to significant species diversity. Not all studies, however, have identified support for ecological opportunity associated with novel intercontinental colonizations. To gain key insights into the drivers of ecological opportunity, we tested whether intercontinental dispersals resulted in ecological opportunity using the Hydrangeaceae-Loasaceae clade, which has numerous centers of diversity across the globe.

Tetragonia tetragonioides extract prevented high-fat diet-induced obesity and changed hepatic and adipose transcriptomic signatures in C57BL/6J male mice.

Obesity, often driven by high-fat diets (HFD), is a major global health issue, necessitating effective preventive measures. Tetragonia tetragonoides, a plant with known medicinal properties, has not been extensively studied for its effects on HFD-induced obesity and related genetic changes in mice. This study explores the impact of Tetragonia tetragonoides extract (TTE; 300 mg/kg) on obesity-related traits in C57BL/6J male mice, with a focus on transcriptomic changes in the liver and white adipose tissue (WAT).

Cannabis use characteristics and associations with problematic use outcomes, quitting-related factors, and mental health among US young adults.

Objective: Given the changes in trends of cannabis use (e.g., product types), this study examined latent classes of young adult use and associations with use-related outcomes.

Knowledge of Accredited Social Health Activists in India: a systematic review and meta analysis of evidence drawn from primary studies published between 2005 and 2022.

Background: Since the inception of the ASHAs in the year 2005, their work horizons have increased from Reproductive, Maternal, Newborn, Child, and Adolescent health (RMNCH + A), Communicable and Non-Communicable Diseases (CD & NCD) to oral health, ophthalmologic care, and other supportive community level healthcare services. The present literature lacks comprehensive understanding and synthesis of domain-wise knowledge of ASHAs and the factors affecting their knowledge. Therefore, this study aimed to synthesize and collate the relevant evidence to understand the overall knowledge of ASHAs.

Clinician perspectives on designing and implementing a hereditary cancer transition clinic.

Early identification of hereditary cancer predisposition in adolescents and young adults represents a unique opportunity to target cancer prevention and improve survival in a population at risk for adverse health outcomes. However, adolescents and young adults face challenges unique to their stage of life that can undermine their transition from pediatric to adult healthcare and lead to interruptions in preventative care. The purpose of this study was to understand expert perspectives on factors relevant to designing and implementing a transition clinic for adolescents and young adults with hereditary cancer predisposition.

Nebulized dexmedetomidine in the treatment of obstetric post-dural puncture headache: two case reports.

Post-dural puncture headache (PDPH) is a debilitating complication of neuraxial anesthesia, particularly prevalent in obstetric patients, usually characterized by a postural headache. PDPH is hypothesized to result from cerebrospinal fluid leakage through a dural puncture, triggering symptoms like neck stiffness and subjective hearing changes. While conservative measures are common for treatment, more refractory cases may require invasive interventions such as an epidural blood patch (EBP).

Global surgery and climate change: how global surgery can prioritise both the health of the planet and its people.

Climate change is an emerging global health crisis, disproportionately affecting low- and middle-income countries (LMICs) where health outcomes are increasingly compromised by environmental stressors such as pollution, natural disasters, and human migration. With a focus on promoting health equity, Global Surgery advocates for expanding access to surgical care and enhancing health outcomes, particularly in resource-limited and disaster-affected areas like LMICs. The healthcare industry-and more specifically, surgical care-significantly contributes to the global carbon footprint, primarily through resource-intensive settings, i.

Young, Empowered & strong (YES): a study protocol paper for a randomized controlled trial of an mHealth symptom monitoring and self-management intervention for adolescent and young adult (AYA) breast cancer survivors.

Background: Compared to older adults with breast cancer (BC), adolescents and young adults (AYAs) develop more aggressive disease necessitating more intensive therapy with curative intent, which is disruptive to planned life trajectories. The burden of unmet needs among AYA BC survivors exists in two domains: (1) symptoms (e.g.

Posttraumatic stress disorder in disaster-exposed youth: examining diagnostic concordance and model fit using ICD-11 and DSM-5 criteria.

Background: Competing definitions of posttraumatic stress disorder (PTSD) have been proposed by ICD-11 and DSM-5; it is unclear which diagnostic model works best for children and adolescents. Although other studies have predicted the impact of these models by approximating the criteria using older measures, this study advances the research by comparing measures designed to assess ICD-11 and DSM-5 criteria in hurricane-exposed youth. This study evaluates ICD-11 and DSM-5 (both the standard and preschool-age) diagnostic models by identifying diagnostic rates, evaluating diagnostic concordance, investigating the predictive value of constructs associated with PTSD (demographics, disaster threat and exposure, functional impairment), and examining model fit.

Associations of daily step count with all-cause mortality and cardiovascular mortality in hypertensive US adults: a cohort study from NHANES 2005-2006.

Background: The health benefits of physical activity, including walking, are well-established, but the relationship between daily step count and mortality in hypertensive populations remains underexplored. This study investigates the association between daily step count and both all-cause and cardiovascular mortality in hypertensive American adults.

Methods: We used data from the National Health and Nutrition Examination Survey 2005-2006, including 1,629 hypertensive participants with accelerometer-measured step counts.

Differences in gut microbial diversity and composition between growth phenotypes of farmed juvenile sandfish, Holothuria scabra.

Background: The observed growth variability of different aquaculture species in captivity hinders its large-scale production. For the sandfish Holothuria scabra, a tropical sea cucumber species, there is a scarcity of information on its intestinal microbiota in relation to host growth, which could provide insights into the processes that affect growth and identify microorganisms with probiotic or biochemical potential that could improve current production strategies. To address this gap, this study used 16 S rRNA amplicon sequencing to characterize differences in gut and fecal microbiota among large and small juveniles reared in floating ocean nurseries.

Red cell distribution width as a cardiovascular risk predictor in adults with hypertension in sub-Saharan Africa.

Red cell distribution width (RDW) quantifies the degree of variation in erythrocyte size, is identified as a potential marker of adverse cardiovascular events, and may be a surrogate marker for assessing cardiovascular disease (CVD) risk in low-resource settings. We evaluated RDW as a predictor of CVD risk compared to the World Health Organization (WHO) CVD risk score among adults with hypertension attending primary healthcare centers (PHCs) in Ghana and Nigeria. Adults with hypertension attending selected PHCs in Ghana and Nigeria participated in a cross-sectional study.

Classroom air quality in a randomized crossover trial with portable HEPA air cleaners.

Background: Children living in communities with lower socioeconomic status and higher minority populations are often disproportionately exposed to particulate matter (PM) compared to children living in other communities.

Objective: We assessed whether adding HEPA filter air cleaners to classrooms with existing HVAC systems reduces indoor air pollution exposure.

Methods: From July 2022 to June 2023, using a block randomized crossover trial of 17 Los Angeles Unified School District elementary schools, classroom PM concentrations were monitored and compared for 99 classrooms with HEPA filter air cleaners and 87 classrooms with non-HEPA filter air cleaners.

Nivolumab Combined with Chemotherapy in FGFR2 and PD-L1 Co-Expressing Metastatic Gastric Cancer: A Prospective Phase 2 NIVOFGFR2 Study.

Background: Immunotherapy is increasingly significant in treating metastatic gastric cancer. This prospective phase 2 study investigates the efficacy and safety of combining nivolumab with chemotherapy in patients with metastatic gastric cancer co-expressing FGFR2 and PD-L1.

Methods: Eligible patients were aged 18 years or older, with previously untreated HER-2 negative, PD-L1 positive, and FGFR2 positive metastatic gastric adenocarcinoma.

Promoted read-through and mutation against pseudouridine-CMC by an evolved reverse transcriptase.

Pseudouridine (Ψ) is an abundant RNA chemical modification that plays critical biological functions. Current Ψ detection methods are limited in identifying Ψs at base-resolution in U-rich sequence contexts, where Ψ occurs frequently. Here we report "Mut-Ψ-seq" that utilizes the classic N-cyclohexyl N'-(2-morpholinoethyl)carbodiimide (CMC) agent and an evolved reverse transcriptase ("RT-1306") for Ψ mapping at base-resolution.

Kyphectomy followed by self-sliding pedicle screw and translumbosacral rod impaction and fixation: a novel growth-friendly technique in myelomeningocele patients.

Introduction: Congenital lumbar kyphosis is present in about 15% of patients with myelomeningocele. Worsening of deformity with complications such as chronic skin ulcers and bone exposure is common. In patients under 8 years of age, treatment becomes even more challenging: in addition to resecting the apex of the kyphotic deformity, we should ideally stabilize the spine with fixation methods that do not interrupt the growth of the rib cage, associated with the challenging pelvic fixation in this population.

Cadmium translocation combined with metabolomics analysis revealed potential mechanisms of MT@MSN-CS and GSH@MSN-CS in reducing cadmium accumulation in rice (Oryza sativa L.) grains.

Applying nano-delivery systems for phytohormones via foliar application has proven effective in reducing grain cadmium (Cd) levels in crops. However, the mechanisms underlying this reduction remain inadequately understood. This study integrated the determination of leaf photosynthetic parameters, Cd translocation analysis, and metabolomics to elucidate the effects of reduced glutathione (GSH) and melatonin (MT), delivered with or without chitosan-encapsulated mesoporous silica nanoparticles (MSN-CS), on grain Cd levels in rice.