The Effect of Dipeptide Repeat Proteins on FUS/TDP43-RNA Condensation in C9orf72 ALS/FTD.

Condensation of RNA binding proteins (RBPs) with RNA is essential for cellular function. The most common familial cause of the diseases ALS and FTD is C9orf72 repeat expansion disorders that produce dipeptide repeat proteins (DPRs). We explore the hypothesis that DPRs disrupt the native condensation behavior of RBPs and RNA through molecular interactions resulting in toxicity.

Enacting an "Empowerment Approach" After Sexual Assault: The Views and Beliefs of Forensic Nurse Examiners and Crisis Support Workers.

Background: Sexual violence is a profoundly disempowering experience. It is essential that survivors are offered access to comprehensive medical care, psychological support, and follow-up in a way that offers them a high level of choice and control.

Aims: There has been little research into how practitioners working in the context of immediate postassault understand empowerment and reflect this in their care delivery.

Blood pressure variability supersedes heart rate variability as a real-world measure of dementia risk.

Blood pressure variability (BPV) and heart rate variability (HRV) have been associated with Alzheimer's Disease and Related Dementias (ADRD) in rigorously controlled studies. However, the extent to which BPV and HRV may offer predictive information in real-world, routine clinical care is unclear. In a retrospective cohort study of 48,204 adults (age 54.

Structural properties of the HNF-1A transactivation domain.

Hepatocyte nuclear factor 1α (HNF-1A) is a transcription factor with important gene regulatory roles in pancreatic β-cells. gene variants are associated with a monogenic form of diabetes (HNF1A-MODY) or an increased risk for type 2 diabetes. While several pancreatic target genes of HNF-1A have been described, a lack of knowledge regarding the structure-function relationships in HNF-1A prohibits a detailed understanding of HNF-1A-mediated gene transcription, which is important for precision medicine and improved patient care.

Initial Results from a New College Substance Use Prevention Program Targeting Externalizing and Internalizing Traits.

College students engage in high rates of risky substance use. Standard college prevention strategies focus on providing feedback about current substance use behaviors and harm reduction strategies but do not address the underlying genetically-influenced risk factors impacting these behaviors. We created an online Personalized Feedback Program (PFP) for college students that targets genetically-influenced externalizing and internalizing risk pathways and provides personalized recommendations and campus resources.

Exploring Intra- and Inter-Regional Interactions in the IDP α-Synuclein Using smFRET and MD Simulations.

Theoretical concepts from polymer physics are often used to describe intrinsically disordered proteins (IDPs). However, amino acid interactions within and between regions of the protein can lead to deviations from typical polymer scaling behavior and even to short-lived secondary structures. To investigate the key interactions in the dynamic IDP α-synuclein (αS) at the amino acid level, we conducted single-molecule fluorescence resonance energy transfer (smFRET) experiments and coarse-grained molecular dynamics (CG-MD) simulations.

Integrating Theory with Education about Genetic Risk for Alcohol Use Disorder: The Effects of a Brief Online Educational Tool on Elements of the Health Belief Model.

Introduction: The utility of genetic risk information relies on the assumption that individuals will use the information to change behavior to reduce risk of developing health problems. Educational interventions designed to target elements of the Health Belief Model have shown to be effective in promoting behaviors for positive outcomes.

Methods: A randomized controlled trial (RCT) was conducted in 325 college students to assess whether a brief, online educational intervention altered elements of the Health Belief Model that are known to be associated with motivations and intentions to change behavior.

Bridging the gap between genetic epidemiological research and prevention: A randomized control trial of a novel personalized feedback program for alcohol and cannabis use.

Background: Risky substance use among college students is widespread and associated with numerous negative consequences. We created an online Personalized Feedback Program (PFP) for college students that targets genetically influenced risk pathways for substance use and provides feedback on four risk domains (Sensation Seeking, Impulsivity, Extraversion, and Neuroticism) along with individualized recommendations and campus resources.

Methods: A pilot randomized controlled trial was conducted to evaluate the effects of the PFP on alcohol and cannabis use.

Apparent Risks of Postural Orthostatic Tachycardia Syndrome Diagnoses After COVID-19 Vaccination and SARS-Cov-2 Infection.

Postural orthostatic tachycardia syndrome (POTS) has been previously described after SARS-CoV-2 infection; however, limited data is available on the relation of POTS with COVID-19 vaccination. Here we show in a cohort of 284,592 COVID-19 vaccinated individuals using a sequence-symmetry analysis, that the odds of POTS are higher 90 days after vaccine exposure than 90 days prior to exposure, and that the odds for POTS are higher than referent conventional primary care diagnoses, but lower than the odds of new POTS diagnosis after SARS-CoV-2 infection. Our results identify a possible association between COVID-19 vaccination and incidence of POTS.

The impact of receiving polygenic risk scores for alcohol use disorder on psychological distress, risk perception, and intentions to reduce drinking.

For the return of polygenic risk scores to become an acceptable clinical practice in psychiatry, receipt of polygenic risk scores must be associated with minimal harm and changes in behavior that decrease one's risk for developing a psychiatric outcome. Data from a randomized controlled trial was used to assess the impact of different levels of hypothetical polygenic risk scores for alcohol use disorder on psychological distress, risk perception, and intentions to change drinking behaviors. The analytic sample consisted of 325 participants recruited from an urban, public university.

Association of blood pressure variability during acute care hospitalization and incident dementia.

Background And Objectives: Recognized as a potential risk factor for Alzheimer's disease and related dementias (ADRD), blood pressure variability (BPV) could be leveraged to facilitate identification of at-risk individuals at a population level. Granular BPV data are available during acute care hospitalization periods for potentially high-risk patients, but the incident ADRD risk association with BPV measured in this setting is unknown. Our objective was to evaluate the relation of BPV, measured during acute care hospitalization, and incidence of ADRD.

Mechanically Ventilated Patients With Coronavirus Disease 2019 Had a Higher Chance of In-Hospital Death If Treated With High-Flow Nasal Cannula Oxygen Before Intubation.

Background: The impact of high-flow nasal cannula (HFNC) on outcomes of patients with respiratory failure from coronavirus disease 2019 (COVID-19) is unknown. We sought to assess whether exposure to HFNC before intubation was associated with successful extubation and in-hospital mortality compared to patients receiving intubation only.

Methods: This single-center retrospective study examined patients with COVID-19-related respiratory failure from March 2020 to March 2021 who required HFNC, intubation, or both.

Condom Use Behaviors, Risk Perception, and Partner Communication Following Oral HIV Self-testing Among Adolescents and Young Adults in Kenya: A Cohort Study.

HIV self-testing (HIVST) can improve testing completion among adolescents and young adults (AYA), although its influence on sexual behaviors is unclear. We evaluated whether HIVST was associated with changes in talking with sexual partners about HIVST, condom use, and HIV risk perception among AYA ages 15-24 years in a study of HIVST distribution through homes, pharmacies, and nightclubs in Nairobi, Kenya. All participants had negative HIVST results.

Evaluating the impact of a new educational tool on understanding of polygenic risk scores for alcohol use disorder.

Introduction: As gene identification efforts have advanced in psychiatry, so have aspirations to use genome-wide polygenic information for prevention and intervention. Although polygenic risk scores (PRS) for substance use and psychiatric outcomes are not yet available in clinical settings, individuals can access their PRS through online direct-to-consumer resources. One of these widely used websites reports that alcohol use disorder is the third most requested PRS out of >1,000 conditions.

Unwanted abortion disclosure and social support in the abortion decision and mental health symptoms: A cross-sectional survey.

Objectives: To assess the extent of unwanted abortion disclosure and levels of social support in the abortion decision and their association with depression, anxiety, and stress.

Study Design: From January to June 2019, we surveyed people presenting for abortion at four clinics in California, New Mexico, and Illinois regarding their experiences accessing abortion. We used multivariable regression to examine associations between unwanted abortion disclosure and social support in the abortion decision, and symptoms of depression, anxiety and stress.

Cardiovascular and hepatic disease associations by magnetic resonance imaging: A retrospective cohort study.

Background: Hepatic disease is linked to cardiovascular events but the independent association between hepatic and cardiovascular disease remains unclear, given shared risk factors.

Methods: This was a retrospective study of consecutive patients with a clinical cardiac MRI (CMR) and a serological marker of hepatic fibrosis, the FIB-4 score, within one year of clinical imaging. We assessed the relations between FIB-4 scores grouped based on prior literature: low (< 1.

Clinical, environmental, and genetic risk factors for substance use disorders: characterizing combined effects across multiple cohorts.

Substance use disorders (SUDs) incur serious social and personal costs. The risk for SUDs is complex, with risk factors ranging from social conditions to individual genetic variation. We examined whether models that include a clinical/environmental risk index (CERI) and polygenic scores (PGS) are able to identify individuals at increased risk of SUD in young adulthood across four longitudinal cohorts for a combined sample of N = 15,134.

Evidence of premature lymphocyte aging in people with low anti-spike antibody levels after BNT162b2 vaccination.

SARS-CoV-2 vaccines have unquestionably blunted the overall impact of the COVID-19 pandemic, but host factors such as age, sex, obesity, and other co-morbidities can affect vaccine efficacy. We identified individuals in a relatively healthy population of healthcare workers (CORALE study cohort) who had unexpectedly low peak anti-spike receptor binding domain (S-RBD) antibody levels after receiving the BNT162b2 vaccine. Compared to matched controls, "low responders" had fewer spike-specific antibody-producing B cells after the second and third/booster doses.

Returning complex genetic risk information to promote better health-related behaviors: a commentary of the literature and suggested next steps.

Genome-wide association studies aim to identify genetic variants that are associated with a disease phenotype in order to enhance precision medicine efforts. Despite the excitement surrounding the promise of precision medicine and interest among the public in accessing personalized genetic information, there has been little effort dedicated to understanding how complex genetic risk information could be incorporated into clinical practice to inform prevention, screening, and treatment. In this article, we briefly summarize the literature on the impact of receiving genetic risk information on health-related behavior, discuss the limitations of these studies, and outline the challenges that will need to be overcome, along with suggested next steps for future studies, to understand the true promise of precision medicine.

Disparities in Geographic Access to Cardiac Rehabilitation in Los Angeles County.

Background Exercise-based cardiac rehabilitation (CR) is known to reduce morbidity and mortality for patients with cardiac conditions. Sociodemographic disparities in accessing CR persist and could be related to the distance between where patients live and where CR facilities are located. Our objective is to determine the association between sociodemographic characteristics and geographic proximity to CR facilities.

Variability independent of mean blood pressure as a real-world measure of cardiovascular risk.

Background: Individual-level blood pressure (BP) variability, independent of mean BP levels, has been associated with increased risk for cardiovascular events in cohort studies and clinical trials using standardized BP measurements. The extent to which BP variability relates to cardiovascular risk in the real-world clinical practice setting is unclear. We sought to determine if BP variability in clinical practice is associated with adverse cardiovascular outcomes using clinically generated data from the electronic health record (EHR).