The impact of common and rare genetic variants on bradyarrhythmia development.

To broaden our understanding of bradyarrhythmias and conduction disease, we performed common variant genome-wide association analyses in up to 1.3 million individuals and rare variant burden testing in 460,000 individuals for sinus node dysfunction (SND), distal conduction disease (DCD) and pacemaker (PM) implantation. We identified 13, 31 and 21 common variant loci for SND, DCD and PM, respectively.

Psychometric evaluation of the Yale-Brown Obsessive-Compulsive Scale in pregnant women.

Purpose: Although many women experience obsessive-compulsive symptoms during the perinatal period, the Yale-Brown Obsessive Compulsive Scale (YBOCS) has not yet been psychometrically evaluated in this population. This study examined the internal consistency, convergent and divergent validity, and factor structure of the YBOCS among pregnant women.

Methods: 256 Women who were 20 to 24 weeks pregnant completed the clinician-administered YBOCS and Mini International Neuropsychiatric Interview (MINI) along with a series of self-report questionnaires including the Edinburgh Postnatal Depression Scale (EPDS), Perinatal Anxiety Screening Scale (PASS) and Obsessive-Compulsive Inventory-Revised (OCI-R).

Identification of Transdiagnostic Childhood Externalizing Pathology Within an Electronic Medical Records Database and Application to the Analysis of Rare Copy Number Variation.

Externalizing traits and behaviors are broadly defined by impairments in self-regulation and impulse control that typically begin in childhood and adolescence. Externalizing behaviors, traits, and symptoms span a range of traditional psychiatric diagnostic categories. In this study, we sought to generate an algorithm that could reliably identify transdiagnostic childhood-onset externalizing cases and controls within a university hospital electronic health record (EHR) database.

Long-term impact of Diabetes Prevention Program interventions on walking endurance.

Objectives: Type 2 diabetes (T2D) and prediabetes are associated with poor walking endurance, a marker of physical function. We aimed to examine the long-term effects of metformin or intensive lifestyle intervention in adults at high risk of T2D on their 6-min walk test (6MWT) performance.

Methods: Participants were randomized in the 3-year Diabetes Prevention Program (DPP) to one of the three groups: lifestyle intervention, metformin, or placebo, and were subsequently followed in the DPP Outcomes Study.

JHU-2545 preferentially shields salivary glands and kidneys during PSMA-targeted imaging.

Purpose: Prostate-specific membrane antigen (PSMA) radioligand therapy is a promising treatment for metastatic castration-resistant prostate cancer (mCRPC). Several beta or alpha particle-emitting radionuclide-conjugated small molecules have shown efficacy in late-stage mCRPC and one, [[177Lu]Lu]Lu-PSMA-617, is FDA approved. In addition to tumor upregulation, PSMA is also expressed in kidneys and salivary glands where specific uptake can cause dose-limiting xerostomia and potential for nephrotoxicity.

Development of a rapid screener to elicit patient preferences for antiseizure medication discontinuation.

Objective: While guidelines encourage individualized discussions of the risks and benefits of antiseizure medication (ASM) withdrawal after a period of seizure-freedom, no formal methods exist for assessing patient preferences. We report the initial development of a rapid patient preferences screener.

Methods: We conducted a mixed-methods study of adults who were ≥1 year seizure-free and seen for epilepsy across three institutions.

Assessing law enforcement officer skills in Crisis Intervention Team (CIT) research: developing and implementing standardized scenarios.

This paper outlines the development of standardized scenarios used to assess the efficacy of Crisis Intervention Team (CIT) training in a randomized, controlled trial. The objective was to create scenarios that accurately simulate mental health crisis situations for law enforcement officers, ensuring that each scenario tests specific CIT skills relevant to real-world encounters. Our process involved building an interdisciplinary team and drawing from the knowledge and experience of professionals in law enforcement, mental health, and performance arts to design a set of scenarios that are both realistic and challenging.

Maternal Gestational Diabetes Mellitus (GDM) Moderates the Association Between Birth Weight and EEG Power in Healthy Term-Age Newborns.

Gestational diabetes mellitus (GDM) affects around 10% of pregnancies in the United States and has been linked to neurodevelopmental sequelae in children. However, there is a paucity of studies investigating early-life neural markers in GDM-exposed infants. This study examined the association of GDM with relative EEG power among healthy term-age neonates collected during natural sleep.

Willingness to Use Oral and Long-Acting Injectable PrEP in Substance-Using Men who have Sex with Men (SU-MSM) in High HIV Incidence Southern U.S. Cities: A NIDA Clinical Trials Network Study.

In Southern U.S. states with high HIV incidence and low HIV Pre-Exposure Prophylaxis (PrEP) uptake, enhanced efforts to increase interest in and willingness to use PrEP are needed.

Informed Consent in Psychedelic-Assisted Therapy.

Humans have long used classical serotonergic psychedelics, such as psilocybin, for a variety of purposes. Entactogens, such as methylenedioxymethamphetamine (MDMA), emerged during the twentieth century and have likewise seen use in a broad range of settings. Interest has arisen in the use of classical psychedelics and entactogens, together termed "psychedelics," for therapeutic purposes in Western clinical settings.

Generating fair, reliable, and accurate neuropsychological test norms for people with HIV in a low- or middle-income country.

Effective neuropsychological assessment of people with HIV (PWH) in low- and middle-income countries (LMICs) is hampered by the unavailability of adequate test norms. We aimed to: (1) develop demographically-corrected (regression-based) South African (SA) normative data for an HIV appropriate neuropsychological test battery for Xhosa home-language speakers; (2) compare the utility of those norms to that of (i) internal standardization norms and (ii) US test publisher norms; and (3) determine the criterion validity of the newly-developed norms. 114 controls and 102 demographically comparable Xhosa home-language people living with HIV completed a well-establised, standard HIV neuropsychological test battery assessing seven cognitive domains.

Unveiling the neglected role of the intensity of acute stress disorder in the prediction of full- and sub-threshold posttraumatic stress disorder: looking beyond the diagnosis.

Purpose: Exposure to traumatic events may lead to the development of Acute Stress Disorder (ASD) within the first month post-trauma in some individuals, while others may not exhibit ASD symptoms. ASD was introduced as a potential early indicator to identify those at higher risk of developing Posttraumatic Stress Disorder (PTSD), however, PTSD can occur in some individuals even without prior ASD. Assessing ASD post-trauma can assist in identifying those who would most benefit from intervention to prevent later PTSD, yet the predictive power of ASD varies across studies, with intensity of ASD symptoms and subthreshold PTSD often less considered.

The relationship between mitochondrial health, telomerase activity and longitudinal telomere attrition, considering the role of chronic stress.

Telomere attrition is a hallmark of biological aging, contributing to cellular replicative senescence. However, few studies have examined the determinants of telomere attrition in vivo in humans. Mitochondrial Health Index (MHI), a composite marker integrating mitochondrial energy-transformation capacity and content, may be one important mediator of telomere attrition, as it could impact telomerase activity, a direct regulator of telomere maintenance.

Spatial proteomic differences in chronic traumatic encephalopathy, Alzheimer's disease, and primary age-related tauopathy hippocampi.

Introduction: Alzheimer's disease (AD), primary age-related tauopathy (PART), and chronic traumatic encephalopathy (CTE) all feature hyperphosphorylated tau (p-tau)-immunoreactive neurofibrillary degeneration, but differ in neuroanatomical distribution and progression of neurofibrillary degeneration and amyloid beta (Aβ) deposition.

Methods: We used Nanostring GeoMx Digital Spatial Profiling to compare the expression of 70 proteins in neurofibrillary tangle (NFT)-bearing and non-NFT-bearing neurons in hippocampal CA1, CA2, and CA4 subregions and entorhinal cortex of cases with autopsy-confirmed AD (n = 8), PART (n = 7), and CTE (n = 5).

Results: There were numerous subregion-specific differences related to Aβ processing, autophagy/proteostasis, inflammation, gliosis, oxidative stress, neuronal/synaptic integrity, and p-tau epitopes among these different disorders.

Bias-Based Bullying Among Sexual and Gender Minority Youth Living With Disabilities.

Both sexual and gender minority youth (SGMY) and youth living with disabilities are disproportionately impacted by bias-based bullying in school settings. While research has separately examined how sexual and gender minority status and disability status are associated with experiences of bullying, very little research has explored the experiences of youth living with these identities simultaneously. This study examined to what extent SGMY report differential experiences of bias-based bullying depending on various identities and the type of disability an individual reports.

Correlates of neurocognitive performance in older adults with chronic pain and negative emotions: baseline data from the problem adaptation therapy for pain (PATH-pain) randomized controlled trial.

Chronic pain is highly prevalent among older adults, is associated with cognitive deficits, and is commonly treated in primary care. We sought to document the extent of impairment across specific neurocognitive domains and its correlates among older adults with chronic pain in primary care. We analyzed baseline data from the Problem Adaptation Therapy for Pain trial, which examined a psychosocial intervention to improve emotion regulation in 100 adults ≥ 60 years with comorbid chronic pain and negative emotions, who did not have evidence of moderate-to-severe cognitive impairment.

The use and operationalization of "structural stigma" in health-related research: A scoping review.

Background: Research that investigates the negative health effects of stigma beyond the individual and interpersonal levels is increasingly using the concept of "structural stigma." This scoping review investigates how the concept of "structural stigma" has been used and operationalized in health-related literature to date in order to characterize its usage and inform future operationalizations.

Methods: A systematic search and screening process identified peer-reviewed, English-language research articles that used the term "structural stigma" available prior to January 1, 2024 in five databases (i.

Molecular biomarkers associated with TBI outcome in individuals of Black racial identity or African ancestry: a narrative review.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide and a major global health concern. In the United States (US), individuals of Black or African American racial identity experience disproportionately higher rates of TBI and suffer from worse post-injury outcomes. Contemporary research agendas have largely overlooked or excluded Black populations, resulting in the continued marginalization of Black patient populations in TBI studies, thereby limiting the generalizability of ongoing research to patients in the US and around the world.

A descriptive examination of rurality in the Environmental influences on Child Health Outcomes Cohort: Implications, illustrations, and future directions.

Purpose: The Environmental influences on Child Health Outcomes (ECHO) Cohort has enrolled over 60,000 children to examine how early environmental factors (broadly defined) are associated with key child health outcomes. The ECHO Cohort may be well-positioned to contribute to our understanding of rural environments and contexts, which has implications for rural health disparities research. The present study examined the outcome of child obesity to not only illustrate the suitability of ECHO Cohort data for these purposes but also determine how various definitions of rural and urban populations impact the presentation of findings and their interpretation.

Pharmacological modulation of dopamine receptors reveals distinct brain-wide networks associated with learning and motivation in non-human primates.

The neurotransmitter dopamine (DA) has a multifaceted role in healthy and disordered brains through its action on multiple subtypes of dopaminergic receptors. How modulation of these receptors influences learning and motivation by altering intrinsic brain-wide networks remains unclear. Here we performed parallel behavioral and resting-state functional MRI experiments after administration of two different DA receptor antagonists in male and female macaque monkeys.

Prediction of Central Post-Stroke Pain by Quantitative Sensory Testing.

Objective: Among patients with acute stroke, we aimed to identify those who will later develop central post-stroke pain (CPSP) versus those who will not (non-pain sensory stroke [NPSS]) by assessing potential differences in somatosensory profile patterns and evaluating their potential as predictors of CPSP.

Methods: In a prospective longitudinal study on 75 acute stroke patients with somatosensory symptoms, we performed quantitative somatosensory testing (QST) in the acute/subacute phase (within 10 days) and on follow-up visits for 12 months. Based on previous QST studies, we hypothesized that QST values of cold detection threshold (CDT) and dynamic mechanical allodynia (DMA) would differ between CPSP and NPSS patients before the onset of pain.

Prescription psychostimulant use, admissions and treatment initiation and retention in pregnant people with opioid use disorder.

While attention deficit hyperactivity disorder is common among people with addiction, the risks and benefits of attention deficit hyperactivity disorder medication in pregnant people with opioid use disorder are poorly understood. Here, using US multistate administrative data, we examined 3,247 pregnant people initiating opioid use disorder treatment, of whom 5% received psychostimulants. Compared to peers not receiving psychostimulants, the psychostimulant cohort had greater buprenorphine (adjusted relative risk 1.