The impact of co-housing on murine aging studies.

Analysis of preclinical lifespan studies often assume that outcome data from co-housed animals are independent. In practice, treatments, such as controlled feeding or putative life-extending compounds, are applied to whole housing units, and as a result, the outcomes are potentially correlated within housing units. We consider intra-class (here, intra-cage) correlation in three published and two unpublished lifespan studies of aged mice encompassing more than 20,000 observations.

Social Determinants, Mental Well-Being, and Disrupted Life Transitions Among Young Adults with Disabling Mental Health Conditions.

This study sought to understand how young adults (age 18-25) with histories of mental health disorders are coping with disrupted transitions to adulthood during the COVID-19 pandemic. A cross-sectional web survey was conducted in March-June 2021 of 967 US young adults with pre-pandemic psychiatric disability to assess their current psychiatric status, interrupted transitions, and associations with social determinants including income, community participation, and social context. Mental health was assessed with the Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder Scale (GAD-7), and PTSD Checklist-Civilian Version.

Exploring a shared vision for success in permanent supportive housing: a community-partnered study in Colorado, USA.

In the United States and within Colorado, the number of persons experiencing homelessness has risen, with over 600,000 counted on a single night in 2023. Limited data integration across healthcare and social services hinders understanding of how permanent supportive housing (PSH) affects health outcomes. Our study in partnership with healthcare experts, housing providers, and a community advisory panel aimed to integrate data from health records, the justice system, and housing case manager notes to create a multidimensional measure of PSH success.

Dung predicts the global distribution of herbivore grazing pressure in drylands.

Dryland grazing sustains millions of people worldwide but, when poorly managed, threatens food security. Here we combine livestock and wild herbivore dung mass data from surveys at 760 dryland sites worldwide, representing independent measurements of herbivory, to generate high-resolution maps. We show that livestock and wild herbivore grazing is globally disconnected, and identify hotspots of herbivore activity across Africa, the Eurasian grasslands, India, Australia and the United States.

Loss of Kmt2c or Kmt2d primes urothelium for tumorigenesis and redistributes KMT2A-menin to bivalent promoters.

Members of the KMT2C/D-KDM6A complex are recurrently mutated in urothelial carcinoma and in histologically normal urothelium. Here, using genetically engineered mouse models, we demonstrate that Kmt2c/d knockout in the urothelium led to impaired differentiation, augmented responses to growth and inflammatory stimuli and sensitization to oncogenic transformation by carcinogen and oncogenes. Mechanistically, KMT2D localized to active enhancers and CpG-poor promoters that preferentially regulate the urothelial lineage program and Kmt2c/d knockout led to diminished H3K4me1, H3K27ac and nascent RNA transcription at these sites, which leads to impaired differentiation.

Prevalence and Temporal Trends of Attention Deficit Hyperactivity Disorder Medication Fills During Pregnancy and Breastfeeding in Denmark.

Background And Objectives: Females of reproductive age are increasingly using attention deficit hyperactivity disorder (ADHD) medication, but its use during pregnancy and breastfeeding is largely unknown. The aim of this study is to examine the prevalence of ADHD medication fills during pregnancy and breastfeeding, including characteristics of these females and cohort differences over time.

Methods: We conducted a descriptive study using Danish nationwide registers.

Detecting early cognitive deficits in preclinical Alzheimer's disease using a remote digital multi-day learning paradigm.

Remote, digital cognitive testing on an individual's own device provides the opportunity to deploy previously understudied but promising cognitive paradigms in preclinical Alzheimer's disease (AD). The Boston Remote Assessment for NeuroCognitive Health (BRANCH) captures a personalized learning curve for the same information presented over seven consecutive days. Here, we examined BRANCH multi-day learning curves (MDLCs) in 167 cognitively unimpaired older adults (age = 74.

Sexual Networks and Behavioral Characteristics of HIV-Positive Male Military Members, Female Sex Workers, and Male Civilians.

Military members and female sex workers (FSWs) may be more likely to acquire or transmit HIV. Mapping HIV transmission across these high-risk populations and identifying behaviors associated with sexual network clustering are needed for effective HIV prevention approaches. A cross-sectional study recruited participants newly diagnosed with HIV among militaries, civilians, and FSWs in Zambia, Senegal, and Democratic Republic of the Congo (DRC).

Specialized pericyte subtypes in the pulmonary capillaries.

Pericytes are essential for capillary stability and homeostasis, with impaired pericyte function linked to diseases like pulmonary arterial hypertension. Investigating pericyte biology has been challenging due to the lack of specific markers, making it difficult to distinguish pericytes from other stromal cells. Using bioinformatic analysis and RNAscope, we identified Higd1b as a unique gene marker for pericytes and subsequently generated a knock-in mouse line, Higd1b-CreERT2, that accurately labels pericytes in the lung and heart.

Lifetime risk and projected burden of dementia.

Understanding the lifetime risk of dementia can inform public health planning and improve patient engagement in prevention. Using data from a community-based, prospective cohort study (n = 15,043; 26.9% Black race, 55.

Rapid discovery of cyclic peptide protein aggregation inhibitors by continuous selection.

Protein aggregates are associated with numerous diseases. Here we report a platform for the rapid phenotypic selection of protein aggregation inhibitors from genetically encoded cyclic peptide libraries in Escherichia coli based on phage-assisted continuous evolution (PACE). We developed a new PACE-compatible selection for protein aggregation inhibition and used it to identify cyclic peptides that suppress amyloid-β42 and human islet amyloid polypeptide aggregation.

Implementation and evaluation of a novel community-based urban mobile health clinic in Toronto, Ontario.

Setting: Despite Canada's single-payer health system, marginalized populations often experience poor health outcomes and barriers to healthcare access. In response, mobile health clinics (MHCs) have been deployed in several cities across Canada. MHCs are well established in the United States; however, little is known about their role and impact in a country with universal healthcare.

Health risk assessment via ingestion of disinfection by-products in drinking water.

Disinfection is a critical process to ensure the safety of drinking water. To curb the spread of various bacteria and viruses, disinfectants are extensively employed in communities, hospitals, sewage treatment plants, and other settings. However, disinfectants can produce disinfection by-products (DBPs) that threaten human health.

Somatic mutation as an explanation for epigenetic aging.

DNA methylation marks have recently been used to build models known as epigenetic clocks, which predict calendar age. As methylation of cytosine promotes C-to-T mutations, we hypothesized that the methylation changes observed with age should reflect the accrual of somatic mutations, and the two should yield analogous aging estimates. In an analysis of multimodal data from 9,331 human individuals, we found that CpG mutations indeed coincide with changes in methylation, not only at the mutated site but with pervasive remodeling of the methylome out to ±10 kilobases.

Left atrial mechanics in youth with chronic kidney disease and similarly aged healthy controls.

Background: In adults with chronic kidney disease (CKD), abnormal left atrial reservoir strain (LASr) is an early, yet clinically significant, indicator of myocardial dysfunction. However, left atrial mechanics are understudied in youth with CKD. The objective of this study was to assess left atrial strain function in youth with CKD and similarly aged, healthy controls.

Basal forebrain innervation of the amygdala: an anatomical and computational exploration.

Theta oscillations of the mammalian amygdala are associated with processing, encoding and retrieval of aversive memories. In the hippocampus, the power of the network theta oscillation is modulated by basal forebrain (BF) GABAergic projections. Here, we combine anatomical and computational approaches to investigate if similar BF projections to the amygdaloid complex provide an analogous modulation of local network activity.

High throughput method for simultaneous screening of membrane permeability and toxicity for discovery of new cryoprotective agents.

Cryoprotective agent (CPA) toxicity is the most limiting factor impeding cryopreservation of critically needed tissues and organs for transplantation and medical research. This limitation is in part due to the challenge of rapidly screening compounds to identify candidate molecules that are highly membrane permeable and non-toxic at high concentrations. Such a combination would facilitate rapid CPA permeation throughout the sample, enabling ice-free cryopreservation with minimal toxicity.

Survival and prognostic factors among different types of liposarcomas based on SEER database.

The aim of this study is to elucidate the disparities in survival and risk factors among different subtypes of liposarcoma, through analysis of epidemiological and prognostic data. The study cohort consisted of 12,822 patients diagnosed with liposarcoma in the United States between 2000 and 2021, whose data were retrieved from the Surveillance, Epidemiology, and End Results (SEER) program. The prognosis for different subtypes of liposarcoma and the associated factors such as age, tumor stage, intervention, gender, tumor grade, location, size, chemotherapy and radiotherapy, were retrieved from the database.

Efficacy of melatonin treatment in a cystic fibrosis mouse model of airway infection.

Approaches to mitigate the severity of infections and of immune responses are still needed for the treatment of cystic fibrosis (CF) even with the success of highly effective modulator therapies. Previous studies identified reduced levels of melatonin in a CF mouse model related to circadian rhythm dysregulation. Melatonin is known to have immunomodulatory properties and it was hypothesized that treatment with melatonin would improve responses to bacterial infection in CF mice.

Action inflexibility and compulsive-like behavior accompany neurobiological alterations in the anterior orbitofrontal cortex and associated striatal nuclei.

The orbitofrontal cortex (OFC) is a large cortical structure, expansive across anterior-posterior axes. It is essential for flexibly updating learned behaviors, and paradoxically, also implicated in inflexible and compulsive-like behaviors. Here, we investigated mice bred to display inflexible reward-seeking behaviors that are insensitive to action consequences.

A broad spectrum Shigella vaccine based on VirG multiepitope region produced in a cell-free system.

Dysentery caused by Shigella species remains a major health threat to children in low- and middle-income countries. There is no vaccine available. The most advanced candidates, i.

Probabilistic nested model selection in pharmacokinetic analysis of DCE-MRI data in animal model of cerebral tumor.

Best current practice in the analysis of dynamic contrast enhanced (DCE)-MRI is to employ a voxel-by-voxel model selection from a hierarchy of nested models. This nested model selection (NMS) assumes that the observed time-trace of contrast-agent (CA) concentration within a voxel, corresponds to a singular physiologically nested model. However, admixtures of different models may exist within a voxel's CA time-trace.

Evaluation of Drug-Drug Interactions in Pharmacoepidemiologic Research.

Drug-drug interactions (DDIs) represent a significant concern for clinical care and public health, but the health consequences of many DDIs remain largely underexplored. This knowledge gap underscores the critical need for pharmacoepidemiologic research to evaluate real-world health outcomes of DDIs. In this review, we summarize the definitions commonly used in pharmacoepidemiologic DDI studies, discuss common sources of bias, and illustrate through examples how these biases can be mitigated.

Long-Term Opioid Therapy and Risk of Opioid Overdose by Derived Clinical Indication in North Carolina, 2006-2018.

Purpose: Long-term opioid therapy (LTOT) has been shown to be associated with opioid overdose, but the definition of LTOT varies widely across studies. We use a rigorous LTOT definition to examine risk of opioid overdose by duration of treatment.

Methods: Data were from a large private health insurance provider in North Carolina linked to mortality records from 2006-2018.