Alternative 3' UTR polyadenylation is disrupted in the rNLS8 mouse model of ALS/FTLD.

Recent research has highlighted widespread dysregulation of alternative polyadenylation in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). Here, we identify significant disruptions to 3` UTR polyadenylation in the ALS/FTLD-TDP mouse model rNLS8 that correlate with changes in gene expression and protein levels through the re-analysis of published RNA sequencing and proteomic data. A subset of these changes are shared with TDP-43 knock-down mice suggesting depletion of endogenous mouse TDP-43 is a contributor to polyadenylation dysfunction in rNLS8 mice.

Delayed primacy recall in AVLT is associated with medial temporal tau PET burden in cognitively unimpaired adults.

Background: Alzheimer's disease (AD) can be diagnosed by in vivo abnormalities of amyloid-β plaques (A) and tau accumulation (T) biomarkers. Previous studies have shown that analyses of serial position performance in episodic memory tests, and especially, delayed primacy, are associated with AD pathology even in individuals who are cognitively unimpaired. The earliest signs of cortical tau pathology are observed in medial temporal lobe (MTL) regions, yet it is unknown if serial position markers are also associated with early tau load in these regions.

Associations Between Peak Expiratory Flow and Community Mobility Loss Among Older Adults in the United States.

Background: Community mobility is a vital patient-centered outcome for older adults living in the community. These deficits in mobility are linked to social isolation, increased hospitalizations, and higher mortality rates. Impaired pulmonary function may be a modifiable risk factor for mobility decline, with existing inequities in lung health potentially contributing disproportionately to mobility loss among Black older adults.

Segregation in hospital care for Medicare beneficiaries by race and ethnicity and dual-eligible status from 2013 to 2021.

Objective: To examine the extent of segregation between hospitals for Medicare beneficiaries by race, ethnicity, and dual-eligible status over time.

Data Sources And Study Setting: We used Medicare inpatient hospital provider data for fee-for-service (FFS) beneficiaries, and the Dartmouth Atlas of Health Care from 2013 to 2021 nationwide, for hospital referral regions (HRRs), and for and hospital service areas (HSAs).

Study Design: We conducted time trend analysis with dissimilarity indices (DIs) for Black (DI-Black), Hispanic (DI-Hispanic), non-White (including Black, Hispanic, and other non-White) (DI-non-White), and dual-eligible (DI-Dual) beneficiaries.

Smoking as a Marker of Comorbid Vulnerability Among Persons with Probable Posttraumatic Stress Disorder Who Engage in Hazardous Drinking.

Persons with posttraumatic stress disorder (PTSD) compared to those without evince high rates of hazardous drinking, or patterns of alcohol consumption that increase the risk for harmful consequences. One potential marker of vulnerability for PTSD-hazardous drinking comorbidity may be smoking behavior. Individuals with PTSD have a higher prevalence of smoking and smoke at higher rates.

Risk of Incident Cancer in Veterans with Diabetes Who Use Metformin Versus Sulfonylureas.

Prior research suggests metformin has anti-cancer effects, yet data are limited. We examined the association between diabetes treatment (metformin versus sulfonylurea) and risk of incident diabetes-related and non- diabetes-related cancers in US veterans. This retrospective cohort study included US veterans, without cancer, aged ≥ 55 years, who were new users of metformin or sulfonylureas for diabetes between 2001 to 2012.

Status of Sepsis Care in European Hospitals: Results from an International Cross-Sectional Survey.

Rationale: Early detection, standardized therapy, adequate infrastructure and strategies for quality improvement should constitute essential components of every hospital's sepsis plan.

Objectives: To investigate the extent to which recommendations from the sepsis guidelines are implemented and the availability of infrastructure for the care of patients with sepsis in acute hospitals.

Methods: A multidisciplinary cross-sectional questionnaire was used to investigate sepsis care in hospitals.

Endocrinologic Dysfunctions and Neuropsychiatric Sequelae in Pediatric Patients With a History of Central Nervous System Infection (ENDLESS): A Prospective Monocentric Study.

Introduction: Central nervous system (CNS) infections represent some of the most critical pediatric health challenges, characterized by high mortality rates and a notable risk of long-term complications. Despite their significance, standardized guidelines for endocrinological follow-up of CNS infection survivors are lacking, leading to reliance on the expertise of individual centers and clinicians.

Materials And Methods: Prospective monocentric observational study conducted at the Fondazione Policlinico Universitario Agostino Gemelli in Rome, Italy.

Scaling and spreading age-friendly care: Early lessons from the VA National Age-Friendly Action Community.

Background: The Age-Friendly Health System (AFHS) initiative seeks to improve care for older adults through assessing and acting on the 4Ms (What Matters, Medication, Mentation, Mobility). The Department of Veterans Affairs (VA) joined the initiative in 2020, and from 2022 to 2023, VA led its first Age-Friendly Action Community, a 7-month online educational series to teach clinicians about implementing the 4Ms across VA care settings.

Methods: The VA Action Community was designed to spread awareness about Age-Friendly care for older Veterans, improve interprofessional team knowledge for providing care guided by the 4Ms, and support AFHS implementation across multiple care settings.

Trajectories of Resilience-Related Traits and Their Impact on Health Outcomes in Schizophrenia: Results From a 4-Year Longitudinal Study.

Background And Hypothesis: For the rapidly growing population of older people living with schizophrenia (PLWS), psychological resilience, or the capacity to adapt to adversity, is an understudied target for improving health. Little is known about resilience and its longitudinal impact on outcomes among PLWS. This study assesses trajectories of resilience-related traits in PLWS and a nonpsychiatric comparison group (NCs) and longitudinal interactions between resilience and health.

Utility of Candidate Genes From an Algorithm Designed to Predict Genetic Risk for Opioid Use Disorder.

Importance: Recently, the US Food and Drug Administration gave premarketing approval to an algorithm based on its purported ability to identify individuals at genetic risk for opioid use disorder (OUD). However, the clinical utility of the candidate genetic variants included in the algorithm has not been independently demonstrated.

Objective: To assess the utility of 15 genetic variants from an algorithm intended to predict OUD risk.

Menopausal hormone therapy is associated with worse levels of Alzheimer's disease biomarkers in APOE ε4-carrying women: An observational study.

Introduction: Menopausal hormone therapy (MHT), along with the apolipoprotein E (APOE) ε4 allele, has been suggested as a possible risk factor for Alzheimer's disease (AD). However, the relationship between MHT and cerebrospinal fluid (CSF) biomarkers is unknown: we investigated this association, and whether APOE ε4 carrier status moderates it.

Methods: In an observational study of 136 cognitively unimpaired female participants (M = 66.

The CLCA1/TMEM16A/Cl- current axis associates with H2S deficiency in diabetic kidney injury.

The role played by anionic channels in diabetic kidney disease (DKD) is not known. Chloride channel accessory 1 (CLCA1) facilitates the activity of TMEM16A (Anoctamin-1), a Ca2+-dependent Cl- channel. We examined if CLCA1/TMEM16A had a role in DKD.

Impact of neighborhood disadvantage on cardiometabolic health and cognition in a community-dwelling cohort.

Introduction: Neighborhood disadvantage may be an important determinant of cardiometabolic health and cognitive aging. However, less is known about relationships among individuals with mild cognitive impairment (MCI).

Methods: The objective of this study is to investigate the relationship between neighborhood disadvantage measured by national Area Deprivation Index (ADI) rank with measures of cardiometabolic health and cognition among Wake Forest (WF) Alzheimer's Disease Research Center (ADRC) participants, with and without MCI.

Enterobactin inhibits microbiota-dependent activation of AhR to promote bacterial sepsis in mice.

Sepsis is a major cause of morbidity and mortality, but our understanding of the mechanisms underlying survival or susceptibility is limited. Here, as pathogens often subvert host defence mechanisms, we hypothesized that this might influence the outcome of sepsis. We used microbiota analysis, faecal microbiota transplantation, antibiotic treatment and caecal metabolite analysis to show that gut-microbiota-derived tryptophan metabolites including indoles increased host survival in a mouse model of Serratia marcescens sepsis.

Multicomponent telerehabilitation program for veterans with multimorbidity: A randomized controlled feasibility study.

Background: Older veterans with multimorbidity experience physical and social vulnerabilities that complicate receipt of and adherence to physical rehabilitation services. Thus, traditional physical rehabilitation programs are insufficient to address this population's heterogenous clinical presentation.

Objective: To evaluate the feasibility and acceptability of a MultiComponent TeleRehabilitation (MCTR) program for older veterans with multimorbidity.

Unveiling the unusual i-motif-derived architecture of a DNA aptamer exhibiting high affinity for influenza A virus.

Non-canonical nucleic acid structures play significant roles in cellular processes through selective interactions with proteins. While both natural and artificial G-quadruplexes have been extensively studied, the functions of i-motifs remain less understood. This study investigates the artificial aptamer BV42, which binds strongly to influenza A virus hemagglutinin and unexpectedly retains its i-motif structure even at neutral pH.

SPRINT Treatment Among Adults With Chronic Kidney Disease From 2 Large Health Care Systems.

Importance: It is unclear whether the effects of intensive vs standard blood pressure (BP) targets seen in clinical trials generalize to patients with chronic kidney disease (CKD) encountered in everyday practice due to differences in the distribution of cardiovascular risk factors and coexisting conditions.

Objective: To evaluate whether the beneficial and adverse effects of intensive vs standard BP control observed in the Systolic Blood Pressure Intervention Trial (SPRINT) are transportable to a target population of adults with CKD in clinical practice.

Design, Setting, And Participants: This comparative effectiveness study identified 2 populations with CKD who met the eligibility criteria for SPRINT between January 1 and December 31, 2019, in the Veterans Health Administration (VHA) and Kaiser Permanente of Southern California (KPSC).

Development of a Japanese version of the patient perceptions of deprescribing - Short form.

Background: Deprescribing is a critical component of clinical practice, especially in geriatric medicine. Nevertheless, the attributes of patients who are prepared for, interested in, and could potentially benefit from deprescribing have not been well examined. The Patient Perceptions of Deprescribing (PPoD) evaluates patients' overall readiness for deprescribing and is complemented by an 11-item validated short form (SF-PPoD).

Prevalence of Depression in Older Adults and the Potential Protective Role of Volunteering: Findings From the LongROAD Study.

Background: As the US population continues to age, depression and other mental health issues have become a significant challenge for healthy aging. Few studies, however, have examined the prevalence of depression in community-dwelling older adults in the United States.

Methods: Baseline data from the Longitudinal Research on Aging Drivers study were analyzed to examine the prevalence and correlates of depression in a multisite sample of community-dwelling adults aged 65-79 years who were enrolled and assessed between July 2015 and March 2017.

Medicare Part D: Major Shifts With the Inflation Reduction Act and a Way Forward.

The Inflation Reduction Act (IRA) of 2022 introduced major changes in the Part D benefit that aim to improve medication access and correct several of the financial misalignments in the current Part D benefit. The changes address financial obligations of Medicare beneficiaries, the federal government, Part D plan sponsors (i.e.

Modifying Informed Consent to Help Address Functional Unmasking in Psychedelic Clinical Trials.

Importance: There is unprecedented clinician, industry, and patient interest in the therapeutic development of psychedelic drugs. This is due to a combination of promising clinical trial results, positive media coverage, and the lack of novel pharmacologic treatments for psychiatric disorders in recent decades. However, the field faces a key methodological challenge: masking participants to treatment conditions in psychedelic clinical trials has been largely unsuccessful.

Feasibility and acceptability for LION, a fully remote, randomized clinical trial within the VA for light therapy to improve sleep in Veterans with and without TBI: An MTBI2 sponsored protocol.

Sleep-wake disturbances frequently present in Veterans with mild traumatic brain injury (mTBI). These TBI-related sleep impairments confer significant burden and commonly exacerbate other functional impairments. Therapies to improve sleep following mTBI are limited and studies in Veterans are even more scarce.

Advancing Delirium Treatment Trials in Older Adults: Recommendations for Future Trials From the Network for Investigation of Delirium: Unifying Scientists (NIDUS).

Objectives: To summarize the delirium treatment trial literature, identify the unique challenges in delirium treatment trials, and formulate recommendations to address each in older adults.

Design: A 39-member interprofessional and international expert working group of clinicians (physicians, nurses, and pharmacists) and nonclinicians (biostatisticians, epidemiologists, and trial methodologists) was convened. Four expert panels were assembled to explore key subtopics (pharmacological/nonpharmacologic treatment, methodological challenges, and novel research designs).