Rescue therapy after failed thrombectomy in medium/distal vessel occlusions: A retrospective analysis of an international, multi-center registry.

Background: There are limited therapeutic options in cases of failed reperfusion (modified thrombolysis in cerebral infarction [mTICI] score < 2b) after stent-retriever and/or aspiration based endovascular treatment (EVT) for acute ischemic stroke. Despite the absence of data supporting its use, rescue therapy (balloon angioplasty and/or stent implantation) is often utilized in such cases. Studies are limited to large vessel occlusions, while the outcomes and complications after rescue therapy in medium/distal vessel occlusions (MDVOs) have not been reported.

Urinary Kidney Injury Biomarker Profiles in Healthy Individuals and After Nephrotoxic and Ischemic Injury.

Two observational studies were conducted to support an initiative to qualify translational kidney safety biomarkers as clinical drug development tools that identify tubular injury prior to changes in estimated glomerular filtration rate (eGFR). Normal healthy volunteers provided three morning spot urine collections over 4 weeks. Patients undergoing surgical resection and intrathoracic cisplatin for malignant pleural mesothelioma provided urine samples pre- and postoperatively at 4, 8, and 12 hours and daily for 6 days.

Systematic Review of Randomized Controlled Trials Evaluating the Use of Platelet-Rich Plasma for Knee Osteoarthritis: Adherence to Minimum Information for Studies Evaluating Biologics in Orthopaedics.

Background: The Minimum Information for Studies Evaluating Biologics in Orthopedics (MIBO) guidelines were developed in May 2017 to encourage improved reporting standards, promote increased transparency and reproducibility, and enhance clinical evaluation capabilities. The MIBO guidelines consist of 23 checklist items considered necessary to critically appraise clinical studies evaluating platelet-rich plasma (PRP).

Purpose: To assess randomized controlled trials that evaluated PRP for the treatment of knee osteoarthritis in order to systematically review their adherence to the MIBO guidelines.

Gentrification, gun violence, and disparities in access to care for shooting victims.

Background: Gentrification is associated with redistribution of shootings but impacts on access to care are unknown. We evaluate the association of gentrification with shooting rates, transport times, and survival in Boston.

Methods: Gentrification was defined using income, housing, and educational attainment from the 2010-2020 census.

Outcomes of venous sinus stenosis stenting in patients with pulsatile tinnitus and sigmoid sinus wall anomalies.

Background: Transverse sinus stenosis (TSS) and sigmoid sinus wall anomalies (SSWAs) are the most common causes of pulsatile tinnitus (PT). While these conditions may co-occur, they usually require different management approaches. This study aims to evaluate whether TSS stenting alone, without targeted treatment of SSWAs, is sufficient to resolve PT in patients presenting with PT, TSS, and SSWAs.

Multi-modal comparison of molecular programs driving nurse cell death and clearance in Drosophila melanogaster oogenesis.

The death and clearance of nurse cells is a consequential milestone in Drosophila melanogaster oogenesis. In preparation for oviposition, the germline-derived nurse cells bequeath to the developing oocyte all their cytoplasmic contents and undergo programmed cell death. The death of the nurse cells is controlled non-autonomously and is precipitated by epithelial follicle cells of somatic origin acquiring a squamous morphology and acidifying the nurse cells externally.

Updated Geriatrics Competencies for Graduating Medical Students: Training Physicians to Provide Age-Friendly Care.

Purpose: Medical student education in geriatrics is a critical need for every doctor-in-training as the population ages, with fewer than 7,000 geriatricians, and older patients, who now approach 20% of the U.S. population, having unique health care needs.

SNP rs6543176 is associated with extreme human longevity but increased risk for cancer.

Using whole-genome sequencing (WGS) might offer insights into rare genetic variants associated with healthy aging and extreme longevity (EL), potentially pointing to useful therapeutic targets. In this study, we conducted a genome-wide association study using WGS data from the Long Life Family Study and identified a novel longevity-associated variant rs6543176 in the SLC9A2 gene. This SNP also showed a significant association with reduced hypertension risk and an increased, though not statistically significant, cancer risk.

Basic Science and Pathogenesis.

Background: Several viruses have been linked to Alzheimer disease (AD) by independent lines of evidence.

Method: Whole genome and whole exome sequences (WGS/WES) derived from brain (3,404 AD cases, 894 controls) and blood (15,612 AD cases, 24,544 controls) obtained from European ancestry (EU), African American (AA), Mexican (HMX), South Asian Indian (IND), and Caribbean Hispanic (CH) participants of the Alzheimer's Disease Sequencing Project (ADSP) and 276 AD cases 3,584 controls (all EU) from the Framingham Heart Study (FHS) that did not align to the human reference genome were aligned to viral reference genomes. A genome-wide association study (GWAS) for viral DNA load was conducted using PLINK software and regression models with covariates for sex, age, ancestry principal components, and tissue source.

Basic Science and Pathogenesis.

Background: Single-nucleus RNA sequencing (snRNAseq) allows for the dissection of the cell type-specific transcriptional profiles of tissue specimens. In this study, we compared gene expression in multiple brain cell types in brain tissue from Alzheimer disease (AD) cases with no or other co-existing pathologies including Lewy body disease (LBD) and vascular disease (VaD).

Method: We evaluated differential gene expression measured from single nucleus RNA sequencing (snRNAseq) data generated from the hippocampus region tissue donated by 11 BU ADRC participants with neuropathologically confirmed AD with or without a co-existing pathology (AD-only = 3, AD+VaD = 6, AD+LBD = 2).

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) has both genetic and environmental risk factors. Gene-environment interaction may help explain some missing heritability. There is strong evidence for cigarette smoking as a risk factor for AD.

Basic Science and Pathogenesis.

Background: We aim to investigate efficacies of Ras homolog (Rho)-associated kinases (ROCK) inhibitors on Alzheimer's disease (AD) pathological proteins in human induced pluripotent stem cell (iPSC)-differentiated human neurons and the P301S tau transgenic mouse model (PS19).

Method: Quantitative liquid chromatography-mass spectrometry (LC-MS/MS) and targeted ELISA were implemented to investigate the effect of treatment with fasudil or its derivatives on the human neurons and brains from PS19 mice. We explored the efficacy of these ROCK inhibitors in reducing tau phosphorylation, and the brain proteomic profiles after their administration in mice.

Basic Science and Pathogenesis.

Background: The Apolipoprotein E ε4 (APOE-ε4) allele is common in the population, but acts as the strongest genetic risk factor for late-onset Alzheimer's disease (AD). Despite the strength of the association, there is notable heterogeneity in the population including a strong modifying effect of genetic ancestry, with the APOE-ε4 allele showing a stronger association among individuals of European ancestry (EUR) compared to individuals of African ancestry (AFR). Given this heterogeneity, we sought to identify genetic modifiers of APOE-ε4 related to cognitive decline leveraging APOE-ε4 stratified and interaction genome-wide association analyses (GWAS).

Basic Science and Pathogenesis.

Background: With a rapidly aging population, South Korea anticipates a surge in Alzheimer disease (AD). However, the genetic basis of AD in Koreans is not well understood.

Method: We sequenced the genomes of 3,540 Koreans (1,583 AD cases and 1,957 controls) older than age 60 and performed a genome-wide association study (GWAS) of AD using logistic regression models that included covariates for age, sex, five ancestry principal components, and an empirical genetic relationship matrix.

Basic Science and Pathogenesis.

Background: T-cell infiltration into the brain parenchyma is associated with hyperphosphorylated tau (p-tau) accumulation in neurodegenerative diseases. Chronic traumatic encephalopathy (CTE) is a progressive tauopathy caused by exposure to repetitive head impacts (RHI). CTE is defined by the perivascular accumulation of p-tau at the cortical sulcal depths and can be stratified into mild and severe pathological stages.

Basic Science and Pathogenesis.

Background: We previously discovered that Aβ accumulates in the cortical/supranuclear region of the lens in people with Alzheimer's Disease (AD) (Goldstein et al., 2003) and Down Syndrome (DS; (Moncaster et al., 2010).

Basic Science and Pathogenesis.

Background: Cardio and cerebrovascular risk factors (CVRFs) increase the risk of cerebrovascular disease and clinical Alzheimer's Disease (AD), and over 70% of the patients with AD coincident cerebrovascular pathology. We previously found that FMNL2 interacts with a burden score of hypertension, diabetes, heart disease, and body mass index (BMI) by altering the normal astroglial-vascular mechanisms that underly amyloid clearance. Stroke, defined by history of a clinical stroke or brain imaging, is a moderately robust risk factor for AD and dementia.

Basic Science and Pathogenesis.

Background: Age is the largest risk factor for late-onset Alzheimer's Disease (LOAD). Although >80 genetic loci have been associated with LOAD, little is known about the age dependencies of these associations except the APOE region.

Method: We performed cross-ancestry and ancestry-specific genome-wide gene-age interaction and age-stratified association study using TOPMed-imputed genome-wide association study (GWAS) data from Alzheimer's Disease Genetics Consortium (ADGC) including 34,833 non-Hispanic Whites (NHW), 7,264 African Americans (AA), 3,232 East Asians (EA), and 2,024 Caribbean Hispanics (CH) aged 60 years and older.

Basic Science and Pathogenesis.

Background: "SuperAgers" are older adults (ages 80+) whose cognitive performance resembles that of adults in their 50s to mid-60s. Factors underlying their exemplary aging are underexplored in large, racially diverse cohorts. Using eight cohorts, we investigated the frequency of APOE genotypes in SuperAgers compared to middle-aged and older adults.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) and AD-related dementias (ADRD) are modulated by gene-environment (GxE) interactions across the lifespan. Variants of specific genes increase AD risk and synergize with lifetime exposure to environmental toxicants ("exposome"), including neurotoxic metals (lead, Pb; cadmium, Cd) and metalloid (As). These metal/metalloid toxicants readily enter the body (e.

Basic Science and Pathogenesis.

Background: There is growing evidence that epigenetic age acceleration may predict late life cognitive decline and dementia, but it is unknown whether this is due to accelerated neurodegeneration or reduction in cognitive resilience. We examined the relationship between epigenetic clocks and domain specific neuropsychological (NP) factor scores, mild cognitive impairment (MCI), Alzheimer's Disease (AD), and all-cause dementia, before and after accounting for plasma total tau (t-tau), a marker of neurodegeneration.

Method: DNA methylation and plasma t-tau (Simoa assay; Quanterix) data from 2091 Framingham Heart Study Offspring cohort participants were generated from blood at the same Exam 8 visit (2005-2008).

Basic Science and Pathogenesis.

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive head impact (RHI) although little is known about its molecular pathogenesis. Previous studies of single neurons showed that private somatic mutations increase both during normal aging and in neurodegenerative disorders, and show diverse mutational patterns.

Method: We applied two orthogonal single-nucleus whole-genome sequencing (snWGS) methods to neurons isolated from the prefrontal cortex of 15 individuals with CTE, and 4 individuals with RHI but no CTE diagnosis, and compared mutational rates and spectra with neurons from neurotypical controls and Alzheimer's disease (AD).

Basic Science and Pathogenesis.

Background: The Alzheimer's Disease Sequencing Project (ADSP) aims to identify genetic variation contributing to the development or protection of Alzheimer's disease (AD) in diverse ancestral populations. The latest ADSP whole genome sequencing (WGS) data release includes over 36,000 individuals from 37 datasets (NIAGADS NG00067.v11 ADSP R4).

Basic Science and Pathogenesis.

Background: Some subjects exhibit AD pathology but remain cognitively intact. This resilience has been associated with cell-type abundance changes, particularly in neurons. We investigated the molecular basis of cognitive resilience by deconvoluting bulk RNA sequencing (RNA-seq) data into multiple brain cell types derived from three brain regions.