Basic Science and Pathogenesis.

Background: Late onset Alzheimer disease is a complex syndrome, genetically, clinically and pathogenetically heterogeneous. Genome Wide association studies have identified risk alleles for AD harboring genes in the endolysosomal network (ELN). We hypothesize that aggregate burden of these endolysosomal risk alleles impacts cell type specific ELN function, thus contributing to LOAD pathogenesis.

Basic Science and Pathogenesis.

Background: Autosomal dominant progranulin (GRN) mutations are a common genetic cause of frontotemporal lobar degeneration. Though clinical trials for GRN-related therapies are underway, there is an unmet need for biomarkers that can predict symptom onset and track disease progression. We previously showed that presymptomatic GRN carriers exhibit thalamocortical hyperconnectivity that increases with age when they are presumably closer to symptom onset.

Basic Science and Pathogenesis.

Background: Compared to the 'neutral' E3, the E4 allele of Apolipoprotein E (APOE) confers up to a 15-fold increase in Alzheimer's Disease (AD) risk. Conversely, the neuroprotective E2 allele decreases AD risk by a similar degree. Here, we aimed to assess the therapeutic potential of cell-type specific allelic 'switching' by investigating the physiological and neuropathological changes associated with an inducible, in vivo APOE4 to APOE2 transition in astrocytes using a novel transgenic mouse model METHOD: The APOE "switch mouse" (APOE4s2) uses the Cre-loxP system to allow for inducible APOE allele switching from E4 to E2.

Basic Science and Pathogenesis.

Background: The human brain is a complex inter-wired system that emerges spontaneous functional fluctuations. In spite of tremendous success in the experimental neuroscience field, a system-level understanding of how brain anatomy supports various neural activities remains elusive.

Method: Capitalizing on the unprecedented amount of neuroimaging data, we present a physics-informed deep model to uncover the coupling mechanism between brain structure and function through the lens of data geometry that is rooted in the widespread wiring topology of connections between distant brain regions.

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.

Search for Fractionally Charged Particles with CUORE.

The Cryogenic Underground Observatory for Rare Events (CUORE) is a detector array comprised by 988 5  cm×5  cm×5  cm TeO_{2} crystals held below 20 mK, primarily searching for neutrinoless double-beta decay in ^{130}Te. Unprecedented in size among cryogenic calorimetric experiments, CUORE provides a promising setting for the study of exotic throughgoing particles. Using the first tonne year of CUORE's exposure, we perform a search for hypothesized fractionally charged particles (FCPs), which are well-motivated by various standard model extensions and would have suppressed interactions with matter.

Geographic Variation in Inpatient Rehabilitation Outcomes After Traumatic Brain Injury.

Objective: To determine whether regional variations exist in functional outcomes of patients with traumatic brain injury (TBI) admitted to inpatient rehabilitation facilities (IRFs) across the United States, while controlling for demographic and clinical variables.

Setting: Inpatient rehabilitation facilities (IRFs) across 4 U.S.

Clinical Manifestations.

Background: Apathy in Alzheimer's disease (AD) is associated with cognitive impairment, particularly executive functions such as selective attention, making it unclear whether apathy should be a separate treatment target. Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) is the largest and most recent trial assessing apathy and cognition. This analysis assessed whether changes in apathy correlated to changes in various cognitive domains in ADMET 2.

Does enteral nutrition protect against stress ulceration in the critically ill?

Purpose Of Review: Critically ill patients are at risk of gastrointestinal bleeding (GIB) due to stress ulceration. Strategies to reduce the risk include administration of prophylactic ulcer healing medications. Enteral nutrition (EN) may be favourably associated with GIB risks.

The Cumulative Burden of Social Risk Factors and 10-Year Change in Quality of Life.

Background: Social risk factors are linked to adverse health outcomes, but their total impact on long-term quality of life is obscure. We hypothesized that a higher burden of social risk factors is associated with greater decline in quality of life over 10 years.

Methods: We examined associations between social risk factors count and decline >5 points in (i) physical component summary, and (ii) mental component summary scores from the Short Form-12 among Black and White participants in the Reasons for Geographic and Racial Differences in Stroke study (n = 14 401).

Unsupervised machine learning analysis to identify patterns of ICU medication use for fluid overload prediction.

Background: Fluid overload (FO) in the intensive care unit (ICU) is common, serious, and may be preventable. Intravenous medications (including administered volume) are a primary cause for FO but are challenging to evaluate as a FO predictor given the high frequency and time-dependency of their use and other factors affecting FO. We sought to employ unsupervised machine learning methods to uncover medication administration patterns correlating with FO.

Risk of Blindness From Temple Filler Injections: Investigating Vascular Anastomoses Between the Deep Temporal and Ophthalmic Arteries.

Purpose: Soft-tissue filler injections, particularly hyaluronic acid, are popular for temple volume restoration. Although uncommon, this area poses risk for vision loss from embolic occlusion. Guidelines recommend injecting into the supraperiosteal plane for safety; however, the deep temporal arteries (DTAs) in this plane pose a risk.

Impact of Hurricanes and Floodings on Mental Health Outcomes Within the United States: A Systematic Review and Meta-Analysis.

Objective: Given the US population concentration near coastal areas and increased flooding due to climate change, public health professionals must recognize the psychological burden resulting from exposure to natural hazards.

Methods: We performed a systematic search of databases to identify articles with a clearly defined comparison group consisting of either pre-exposure measurements in a disaster-exposed population or disaster-unexposed controls, and assessment of mental health, including but not limited to, depression, post-traumatic stress (PTS), and anxiety.

Results: Twenty-five studies, with a combined total of 616 657 people were included in a systematic review, and 11 studies with a total of 2012 people were included in a meta-analysis of 3 mental health outcomes.

Population Pharmacokinetics and Pharmacodynamics of Sotalol Following Expedited Intravenous Loading in Patients With Atrial Arrhythmias.

Sotalol, a class III antiarrhythmic agent, is used to maintain sinus rhythm in patients with atrial fibrillation or atrial flutter (AFIB/AFL). Despite its efficacy, sotalol's use is limited by its potential to cause life-threatening ventricular arrhythmias due to QT interval prolongation. Traditionally, sotalol administration required hospitalization to monitor these risks.

Sex-Specific Effects in Acute Nicotine Vapor Exposure on Binge Drinking and Activity in the Central Amygdala and Ventral Tegmental Area.

Introduction: The increasing prevalence of electronic nicotine delivery systems and alcohol drinking has led to increases in nicotine and alcohol co-use. However, the impact of ENDs on brain activity and binge drinking behavior is not fully understood.

Aims And Methods: We subjected female and male C57BL/6J mice to a voluntary drinking and electronic nicotine vapor exposure paradigm.

Predictors of Medical Mistrust Among Surrogate Decision-Makers of Patients in the ICU at High Risk of Death: A Pilot Study.

Background: Medical mistrust may worsen communication between ICU surrogate decision-makers and intensivists. The prevalence of and risk factors for medical mistrust among surrogate decision-makers are not known.

Research Question: What are the potential sociodemographic risk factors for high medical mistrust among surrogate decision-makers of critically ill patients at high risk of death?

Study Design And Methods: In this pilot cross-sectional study conducted at a single academic medical center between August 2022 and August 2023, adult patients admitted to the medical ICU and their surrogate decision-makers were enrolled.

The Historical Case for a Strong and Diverse Neurology Clerkship Leadership Team.

The role of the clerkship director has evolved significantly over the past century and now requires a diverse range of skills to meet the rigorous standards set by national accrediting bodies such as the Liaison Committee on Medical Education. We conducted a historical exploration, spanning the past 43 years, of the educational practices in the Neurology Department at Johns Hopkins University School of Medicine. We learned that no entity is responsible for documenting the history of the clerkship.

A new measure of professional caregiver coping in long-term care: The LTC COPE.

Introduction: The professional caregiver workforce (nursing assistants and personal care aides) is critical to quality of care and quality of life in nursing home (NH) and assisted living (AL) settings. The work is highly stressful, so improving responses to stress in this workforce could contribute to satisfaction and retention. This research developed a coping measure appropriate for the diverse professional caregiver workforce.

Stress-related coping and its relationship to well-being in nursing assistants and personal care aides in nursing homes and assisted living.

Introduction: Professional caregivers (nursing assistants and personal care aides) in nursing homes (NH) and assisted living (AL) provide the majority of long-term residential care for persons with Alzheimer's disease and related dementias. Their work is stressful, but until recently, no measures were available to assess stress in this workforce. Using the new Long-Term Care Cope (LTC COPE) scale, this study evaluates the relationship of coping with staff demographic characteristics and outcomes; the findings can be used to develop and evaluate interventions to improve staff well-being.

Alternate definitions of adverse pathology to predict a very high risk of metastasis in men with intermediate- and low-risk prostate cancer.

Background: Adverse pathology (AP) is often used as an intermediate end point for long-term outcomes in men with prostate cancer (PCa) who are active surveillance candidates. The association between a commonly used AP definition and long-term outcomes was tested, which identified definitions more strongly linked to a high risk of metastasis.

Methods: Data were reviewed from the Shared Equal Access Regional Cancer Hospital cohort of men undergoing radical prostatectomy (RP) from 1988 to 2020 at nine Veterans Affairs hospitals.

Comorbid conditions and survival among Black women with ovarian cancer.

Background: Black women with epithelial ovarian cancer (EOC) have worse survival and a higher burden of comorbid conditions compared with other racial groups. This study examines the association of comorbid conditions and medication use for these conditions with survival among Black women with EOC.

Methods: In a prospective study of 592 Black women with EOC, the Charlson comorbidity index (CCI) based on self-reported data, three cardiometabolic comorbidities (type 2 diabetes, hypertension, and hyperlipidemia), and medication use for each cardiometabolic comorbidity were evaluated.

Sex Differences, Menses-Related Symptoms and Menopause in Disorders of Gut-Brain Interaction.

Background: Disorders of gut-brain interaction (DGBI) predominate in women, but little is known about sex differences in menses-related or menopause symptoms.

Methods: Using data from the Rome Foundation Global Epidemiology Survey, we assessed Rome IV DGBI symptoms in individuals in 26 countries who met criteria for ≥ 1 of 5 DGBI: irritable bowel syndrome (IBS), functional dyspepsia (FD), functional constipation (FC), functional diarrhea (FDr), or functional bloating (FB). Participants included pre- and post-menopausal women with DGBI and age-matched men.

Food Allergy Prevalence in Two Population-Based UK Cohorts Born 12 Years Apart.

Background: Adverse food reactions include food allergy (FA; immune-mediated) and food intolerances (non-immune-mediated). FA are classified into IgE- and non-IgE-mediated FA. There is limited information available about changes in FA prevalence over time.