Polygenic burden of short tandem repeat expansions promotes risk for Alzheimer's disease.

Studies of the genetics of Alzheimer's disease (AD) have largely focused on single nucleotide variants and short insertions/deletions. However, most of the disease heritability has yet to be uncovered, suggesting that there is substantial genetic risk conferred by other forms of genetic variation. There are over one million short tandem repeats (STRs) in the genome, and their link to AD risk has not been assessed.

A Novel Approach to the Management of an Intra-abdominal Abscess: A Case Report and Literature Review.

Exploratory laparotomies for blunt or penetrating trauma often result in significant morbidity. Despite advancements in resuscitation, surgical techniques, and antibiotics, intra-abdominal abscesses remain a serious complication, contributing to poor outcomes and extended hospital stays. Percutaneous computed tomography-guided drainage is the standard treatment for abscesses, offering high success rates and low morbidity.

Successful Percutaneous Coronary Stenting in End-Stage Liver Disease Patients Awaiting Liver Transplantation.

Coronary artery disease (CAD) is associated with poor outcomes after orthotopic liver transplantation (OLT). We report on six high-risk end-stage liver disease (ESLD) patients who underwent percutaneous coronary intervention (PCI) with bare metal stents during the preoperative evaluation process. There was no mortality or major adverse cardiac event (MACE) within 90 days of OLT.

Management of asynchronous multifocal adult glioblastoma with loss of BRAF -mutant clonality: a case report.

Glioblastoma (GBM) classification involves a combination of histological and molecular signatures including IDH1/2 mutation, TERT promoter mutation, and EGFR amplification. Non-canonical mutations such as BRAF, found in 1-2% of GBMs, activate the MEK-ERK signaling pathway. This mutation can be targeted by small molecule inhibitors, offering therapeutic potential for GBM.

Number of children and dementia risk: a causal mediation analysis using data from the HUNT study linked with national registries in Norway.

Background: Childlessness, as well as having a high number of children, has been reported to be associated with an elevated risk of dementia compared to having 2-3 children. The mechanisms underlying these relationships are not well understood and may be mediated by different midlife risk factors. We examined the mediating role of various factors on the relationship between the number of children and dementia risk.

Retinoids and retinoid-binding proteins: Unexpected roles in metabolic disease.

Alterations in tissue expression levels of both retinol-binding protein 2 (RBP2) and retinol-binding protein 4 (RBP4) have been associated with metabolic disease, specifically with obesity, glucose intolerance and hepatic steatosis. Our laboratories have shown that this involves novel pathways not previously considered as possible linkages between impaired retinoid metabolism and metabolic disease development. We have established both biochemically and structurally that RBP2 binds with very high affinity to very long-chain unsaturated 2-monoacylglycerols like the canonical endocannabinoid 2-arachidonoyl glycerol (2-AG) and other endocannabinoid-like substances.

Development of nebulized inhalation delivery for fusion-inhibitory lipopeptides to protect non-human primates against Nipah-Bangladesh infection.

Nipah virus (NiV) is a lethal zoonotic paramyxovirus that can be transmitted from person to person through the respiratory route. There are currently no licensed vaccines or therapeutics. A lipopeptide-based fusion inhibitor was developed and previously evaluated for efficacy against the NiV-Malaysia strain.

Protocol for recording physiological signals from the human cerebellum using electroencephalography.

As Purkinje cells of the cerebellum have a very fast firing rate, techniques with high temporal resolution are required to capture cerebellar physiology. Here, we present a protocol to record physiological signals in humans using cerebellar electroencephalography (cEEG). We describe steps for electrode placement and recording.

Apixaban to Prevent Covert Infarcts After Cryptogenic Stroke in Patients With Atrial Cardiopathy: A Secondary Analysis of the ARCADIA Randomized Clinical Trial.

Importance: In the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) randomized clinical trial, anticoagulation did not prevent recurrent stroke among patients with a recent cryptogenic stroke and atrial cardiopathy. It is unknown whether anticoagulation prevents covert infarcts in this population.

Objective: To test the use of apixaban vs aspirin for prevention of nonlacunar covert infarcts after cryptogenic stroke in patients with atrial cardiopathy.

Exploring the role of T cells in Alzheimer's and other neurodegenerative diseases: Emerging therapeutic insights from the T Cells in the Brain symposium.

This proceedings article summarizes the inaugural "T Cells in the Brain" symposium held at Columbia University. Experts gathered to explore the role of T cells in neurodegenerative diseases. Key topics included characterization of antigen-specific immune responses, T cell receptor (TCR) repertoire, microbial etiology in Alzheimer's disease (AD), and microglia-T cell crosstalk, with a focus on how T cells affect neuroinflammation and AD biomarkers like amyloid beta and tau.

Hearing Loss and Discrimination: Evidence of Intersectionality in the All of Us Research Program.

Objectives: Hearing loss (HL) has significant implications on social functioning. Here, we study the relationship between HL, race, and these combined categories as risk factors for discrimination in the large national All of Us cohort.

Methods: The National Institutes of Health All of Us dataset was analyzed after including individuals who completed the Everyday Discrimination Survey between November 2021 and January 2022.

Distinct CD8 T-cell types Associated with COVID-19 Severity in Unvaccinated HLA-A2 Patients.

Although emerging data have revealed the critical role of memory CD8 T cells in preventing and controlling SARS-CoV-2 infection, virus-specific CD8 T-cell responses against SARS-CoV-2 and its memory and innate-like subsets in unvaccinated COVID-19 patients with various disease manifestations in an HLA-restricted fashion remain to be understood. Here, we show the strong association of protective cellular immunity with mild COVID-19 and unique cell types against SARS-CoV-2 virus in an HLA-A2 restricted manner. ELISpot assays reveal that SARS-CoV-2-specific CD8 T-cell responses in mild COVID-19 patients are significantly higher than in severe patients, whereas neutralizing antibody responses against SARS-CoV-2 virus significantly correlate with disease severity.

Association of a multiplex immune marker panel with incident cognitive impairment and dementia: The Northern Manhattan Study.

Objective: To determine whether a panel of immune markers adds significant information to known correlates of risk of dementia and cognitive impairment.

Background: The impact of immune mechanisms on dementia risk is incompletely characterized.

Design/methods: A subsample of the Northern Manhattan Study, a prospective cohort study in the racially/ethnically diverse population of New York City, underwent comprehensive neuropsychological testing up to three times, at approximately 5-year intervals.

Neural Correlates of Irritability and Potential Moderating Effects of Inhibitory Control.

Background: Irritability affects up to 20% of youth and is a primary reason for referral to pediatric mental health clinics. Irritability is thought to be associated with disruptions in processing of reward, threat, and cognitive control; however, empirical study of these associations at both the behavioral and neural level have yielded equivocal findings that may be driven by small sample sizes and differences in study design. Associations between irritability and brain connectivity between cognitive control and reward- or threat-processing circuits remain understudied.

Management of Labral Tears in the Hip: A Consensus Statement.

Background: Inconsistencies in the workup of labral tears in the hip have been shown to result in a delay in treatment and an increased cost to the medical system.

Purpose: To establish consensus statements among Canadian nonoperative/operative sports medicine physicians via a modified Delphi process on the diagnosis, nonoperative and operative management, and rehabilitation and return to play (RTP) of those with labral tears in the hip.

Study Design: A consensus statement.

Characterizing Wellness Initiatives in Academic Radiation Oncology Departments.

Purpose: Burnout is prevalent in radiation oncology (RO), and an increased focus on promoting physician wellness and formalizing wellness-directed efforts has transpired in recent years. We aimed to characterize current wellness leadership positions and efforts within academic RO departments.

Methods And Materials: Academic RO department chairs were contacted to inquire whether they had a departmental wellness leader with a request for leader contact information, if applicable.

The Association Between Hearing Loss and Depression in a Large Electronic Health Record System.

Objective: Hearing loss (HL) is associated with depression, but existing datasets are limited by the type of data available for both hearing and mental health conditions. The purpose of this study is to determine if there is an association between HL and depressive disorders within a large bi-institutional electronic health record (EHR) system containing more granular diagnostic information.

Study Design: Cross-sectional epidemiologic study.

Protocol for identifying Dicer as dsRNA binding and cleaving reagent in response to transfected dsRNA.

Mammalian Dicer has been proved to be functional on double-stranded RNAs (dsRNAs) and involved in antiviral immunity or immune regulation. Here, we present a protocol for identifying Dicer as a dsRNA binding and cleaving factor to transfected dsRNA in cell lines, based on small RNA sequencing (RNA-seq) and dsRNA-immunoprecipitation (dsRNA-IP). We detail both experimental processes and analysis on small RNA-seq data.

Plant Compounds Inhibit the Growth of W12 Cervical Precancer Cells Containing Episomal or Integrant HPV DNA; Tanshinone IIA Synergizes with Curcumin in Cervical Cancer Cells.

This study explores the effects of plant compounds on human papillomavirus (HPV)-induced W12 cervical precancer cells and bioelectric signaling. The aim is to identify effective phytochemicals, both individually and in combination, that can prevent and treat HPV infection and HPV associated cervical cancer. Phytochemicals were tested using growth inhibition, combination, gene expression, RT PCR, and molecular docking assays.

Investigations of Long-Acting Formulations in Children, Adolescents, and Pregnant Women: A Systematic Review.

Long-acting and extended-release drug delivery strategies have greatly improved treatment for a variety of medical conditions. Special populations, specifically infants, children, young people, and pregnant and postpartum women, could greatly benefit from access to these strategies but are often excluded from clinical trials. We conducted a systematic review of all clinical studies involving the use of a long-acting intramuscular injection or implant in infants, children, young people, and pregnant and postpartum people.

Model-Assisted Spleen Contouring for Assessing Splenomegaly in Myelofibrosis: A Fast and Reproducible Approach to Evaluate Progression and Treatment Response.

: Accurate and reproducible spleen volume measurements are essential for assessing treatment response and disease progression in myelofibrosis. This study evaluates techniques for measuring spleen volume on abdominal MRI. : In 20 patients with bone marrow biopsy-proven myelofibrosis, 5 observers independently measured spleen volume on 3 abdominal MRI pulse sequences, 3D-spoiled gradient echo T1, axial single-shot fast spin echo (SSFSE) T2, and coronal SSFSE T2, using ellipsoidal approximation, manual contouring, and 3D nnU-Net model-assisted contouring comparing coefficients of variation.