Adverse childhood experiences and defensive gun use: The indirect role of threat sensitivity and depressive symptoms.

Background/purpose: Adverse childhood experiences (ACEs) have been linked to various detrimental life outcomes, including an increase in threat sensitivity and depressive symptoms. Studies have also found an association between ACEs and firearm ownership. To date, no study has assessed whether ACEs have direct or indirect effects on defensive gun use (DGU) through these risk factors.

Technical and management coaching for government institutions: Lessons learned and health systems transformations across 8 countries in sub-Saharan Africa and India.

Traditional engagement with local governments often relies on financial and human resources from international or local partners, leading to direct implementation by organizations, which can hinder sustainability. While some organizations include sustainability indicators, few focus on transferring technical and financial ownership to governments. The Challenge Initiative (TCI) uses a phased coaching model-lead, assist, observe, and monitor-to build local government capacity for scaling family planning (FP) and adolescent and youth sexual and reproductive health (AYSRH) programs.

Basic Science and Pathogenesis.

Background: While immune function is known to play a mechanistic role in Alzheimer's disease (AD), whether immune proteins in peripheral circulation influence the rate of amyloid-b (Aβ) progression remains unknown.

Method: Using the Baltimore Longitudinal Study of Aging (BLSA; n = 196; mean follow-up: 5 years/4 scans), we identified immune-related proteins in plasma (candidate proteins) related to rates of change in cortical Aβ levels, as measured by C-PiB PET. Along with identifying genetic variants that contributed to candidate protein associations, characterizing their relationships with tau-PET and changes in ADRD biomarkers (Aβ, NfL, GFAP, pTau-181), and assessing their expression patterns in human microglia, we leveraged data from the Atherosclerosis Risk in Communities (ARIC) study to determine if changes in candidate protein levels precede Ab = β onset (n = 272), and whether they predict 20-year dementia risk during mid-life (n = 11,596) and 8-year dementia risk during late-life (n = 4,288).

Basic Science and Pathogenesis.

Background: The ε4 allele of the apolipoprotein E (APOE) gene is the strongest genetic determinant for Alzheimer's disease and cognitive function in nearly all human populations, yet inconsistent effects have been reported in South Asians. The population of India has admixed genetic ancestry with most people falling on a North/South cline and having varying proportions of Ancestral North Indian (ANI) and Ancestral South Indian (ASI) ancestries, and those in east of India fall off the cline due to ancestry from additional ancestral populations. This study examined the ε4 association with cognitive function across 18 states/union territories of India and investigated whether ancestral background modulates ε4 association with cognitive function in 2,590 participants from the Longitudinal Aging Study in India - Diagnostic Assessment of Dementia (LASI-DAD).

Clinical Manifestations.

Background: Prior longitudinal studies among older adults have documented associations between hearing loss and changes in brain morphology. Whether interventions involving hearing aids can reduce age-related atrophy is unknown. A substudy within the Aging and Cognitive Health Evaluation in Elders (ACHIEVE, Clinicaltrials.

Clinical Manifestations.

Background: Hearing loss is highly prevalent and can have significant consequences for older adults aging with cognitive impairment. However, few older adults use hearing aids and disparities in care exist by race, ethnicity, and socioeconomic position. To understand the intersection of hearing loss and cognitive impairment with the ultimate goal of developing an affordable, accessible hearing care intervention responsive to the needs of end-users, a series of semi-structured interviews was conducted.

Basic Science and Pathogenesis.

Background: The prevalence of dementia in India is approximately 7.4% among those aged 60 years and older, yet little is known about genetic risk factors for dementia in this population. Examining genetic variants at higher frequency in India than other ancestries (i.

Clinical Manifestations.

Background: Higher level of cognitive reserve (CR), measured using proxies such as years of education or literacy, is associated with reduced risk of Mild Cognitive Impairment (MCI) and dementia. Little is known about how CR and other lifestyle factors impact non-cognitive outcomes, including depression and other neuropsychiatric symptoms (e.g.

Clinical Manifestations.

Background: How clinicians discuss, document, and diagnose health concerns within a visit shapes patient perceptions of their health conditions. Undiagnosed hearing loss among older adults with dementia or cognitive concerns may exacerbate neuropsychiatric symptoms and care challenges. This study investigates clinician documentation of hearing concerns and whether documentation, diagnosis, and referral vary for older adults with dementia/cognitive concerns.

Clinical Manifestations.

Background: Although it is well established that lower cognitive performance, on average, is associated with a greater risk of developing Alzheimer's disease (AD) dementia, it is unclear whether distinct cognitively-defined subgroups exist among non-demented older adults and whether such profiles map onto distinct AD neuroimaging measure profiles.

Method: The sample consisted of 167 non-demented older adults from the BIOCARD study with comprehensive neuropsychological and clinical evaluations, amyloid PET and brain MRI scans. The MRI measure included: global cortical volume in AD-signature regions and a medial-temporal lobe composite; resting-state functional connectivity within 5 large-scale cognitive networks; global white matter microstructure, index by fractional anisotropy (FA) and radial diffusion (RD) on DTI scans; and global white matter hyperintensity (WMH) volume on FLAIR scans.

Clinical Manifestations.

Background: Subjective memory concerns (SMC) may be a sensitive marker of future cognitive declines. However, there are multiple factors that can impact the predictive utility of SMC. Prior studies have demonstrated the effect of depression on SMC.

Health-seeking behaviours and traditional healer practices for snakebite in rural and tribal communities in southern India.

Background: Nearly 60 000 Indians die of snakebite envenoming each year. Most deaths occur in rural communities and remote tribal settlements. We describe snakebite-related epidemiology and health-seeking behaviours in a rural (Timiri) and remote tribal block (Jawadhu Hills) in Tamil Nadu, India.

A surrogate ELISA to select high titer human convalescent plasma for treating immunocompromised patients infected with SARS-CoV-2 variants of concern.

Background: The emergence of new SARS-CoV-2 variants poses a new challenge for the treatment of immunocompromised patients against COVID-19. In this context, high titer COVID-19 Convalescent Plasma (CCP) is one of the few available therapeutics for these patients. We have revisited the selection of CCP samples and its efficacy against Omicron XBB.

The use of patient-generated health data in the management of low anterior resection syndrome: a qualitative study.

Background: The cornerstone of low anterior resection syndrome (LARS) treatment is self-management, which requires patient engagement. Colorectal surgeons and nurses may use patient-generated health data (PGHD) to help guide patients in their use of self-management strategies for LARS. However, the perspectives of LARS experts on the use of PGHD remain largely unexplored.

"They talked to me like I was dirt under their feet:" Treatment and withdrawal experiences of incarcerated pregnant people with opioid use disorder in four U.S. states.

Background: Many pregnant individuals with opioid use disorder (OUD) spend time in jail, yet access to standard of care medications for OUD (MOUD) in jail is limited. Though qualitative studies of non-incarcerated pregnant and non-pregnant incarcerated individuals with OUD demonstrate complexities that must be considered in delivering effective care, studies with pregnant, incarcerated patients with OUD are lacking.

Methods: We conducted semi-structured qualitative interviews from October 2020-November 2021 with pregnant and postpartum people with OUD who were currently or previously in jail in Florida, Maryland, Ohio, and Virginia.

Is severe maternal morbidity a risk factor for postpartum hospitalization with mental health or substance use disorder diagnoses? Findings from a retrospective cohort study in Maryland: 2016-2019.

Background: Perinatal mental health conditions and substance use are leading causes, often co-occurring, of pregnancy-related and pregnancy-associated deaths in the United States. This study compares odds of hospitalization with a mental health condition or substance use disorder or both during the first year postpartum between patients with and without severe maternal morbidity (SMM) during delivery hospitalization.

Methods: Data are from the Maryland's State Inpatient Database and include patients with a delivery hospitalization during 2016-2018 (n = 197,749).

Addressing Methodological Challenges in Follow-Up RCTs During the COVID-19 Pandemic: The Impact of the Good Behavior Game and MyTeachingPartner™ on Teacher Burnout and Self-Efficacy.

Retention of early career teachers is a critical issue in education, with burnout and self-efficacy serving as important precursors to teachers leaving the field. An integration of the PAX Good Behavior Game (GBG; Barrish et al., 1969) and MyTeachingPartner (MTP; Allen et al.

Influence of Neighborhood Socioeconomic Deprivation on Effectiveness of an Intensive Lifestyle Intervention.

Objective: To assess the influence of neighborhood socioeconomic deprivation on the effectiveness of an intensive lifestyle intervention (ILI) in the Look AHEAD trial.

Research Design And Methods: Look AHEAD randomized adults with overweight/obesity and type 2 diabetes to ILI for weight loss, or Diabetes Support and Education (DSE). We linked participant data from four study sites to the 2000 United States Census to generate a neighborhood socioeconomic deprivation score.

Long COVID in transgender and gender nonbinary people in the United States.

Despite recommendations in the US National Research Action Plan on Long COVID, gender identity is rarely reported in research and surveillance used to guide public health programming and clinical care. We analyzed data from a cross-sectional study of COVID-19 in a nationwide sample of transgender and nonbinary (TNB) people (N = 2,134). Participants were surveyed between June 14, 2021 and May 1, 2022.

Coupling metabolomics and exome sequencing reveals graded effects of rare damaging heterozygous variants on gene function and human traits.

Genetic studies of the metabolome can uncover enzymatic and transport processes shaping human metabolism. Using rare variant aggregation testing based on whole-exome sequencing data to detect genes associated with levels of 1,294 plasma and 1,396 urine metabolites, we discovered 235 gene-metabolite associations, many previously unreported. Complementary approaches (genetic, computational (in silico gene knockouts in whole-body models of human metabolism) and one experimental proof of principle) provided orthogonal evidence that studies of rare, damaging variants in the heterozygous state permit inferences concordant with those from inborn errors of metabolism.

Maternal and infant predictors of human milk macronutrient and energy concentrations in rural Bangladesh: an observational cohort study.

Background: Human milk macronutrient (protein, fat, and carbohydrate) and energy concentrations vary based on maternal and infant factors and time postpartum.

Objective: To determine the change in milk macronutrient and energy concentrations from approximately 2 to 5 months postpartum and identify factors associated with this variation among a lactation cohort in Bangladesh.

Methods: In this prospective observational lactation cohort in rural Sylhet, Bangladesh, we collected hand-expressed mid-feed human milk samples and analyzed macronutrient concentrations using mid-infrared spectroscopy.

Modified dosing schedule efficacy of fosmidomycin and clindamycin against murine malaria Plasmodium berghei.

Fosmidomycin and clindamycin target the Plasmodium apicoplast. Combination clinical trials have produced mixed results with the primary problem being the recrudescent infection frequency by day 28. Given that antibiotic efficacy against bacterial infections often depends on the constant drug presence over several days, we hypothesized that the antimalarial blood or liver stage efficacy of fosmidomycin and clindamycin could be improved by implementing a more frequent dosing schedule.

Protective antibodies target cryptic epitope unmasked by cleavage of malaria sporozoite protein.

The most advanced monoclonal antibodies (mAbs) and vaccines against malaria target the central repeat region or closely related sequences within the circumsporozoite protein (PfCSP). Here, using an antigen-agnostic strategy to investigate human antibody responses to whole sporozoites, we identified a class of mAbs that target a cryptic PfCSP epitope that is only exposed after cleavage and subsequent pyroglutamylation (pGlu) of the newly formed N terminus. This pGlu-CSP epitope is not targeted by current anti-PfCSP mAbs and is not included in the licensed malaria vaccines.