Single-cell analysis of cerebrospinal fluid reveals common features of neuroinflammation.

Neuroinflammation is often characterized by immune cell infiltrates in the cerebrospinal fluid (CSF). Here, we apply single-cell RNA sequencing to explore the functional characteristics of these cells in patients with various inflammatory, infectious, and non-inflammatory neurological disorders. We show that CSF is distinct from the peripheral blood in terms of both cellular composition and gene expression.

Lung development genes, adult lung function and cognitive traits.

Lower lung function is associated with lower cognitive function and an increased risk of dementia. This has not been adequately explained and may partly reflect shared developmental pathways. In UK Biobank participants of European ancestry, we tested the association between lung function measures (forced vital capacity and forced expiratory volume in 1 s to forced vital capacity ratio; = 306 476) and cognitive traits including nine cognitive function test scores ( = 32 321-428 609), all-cause dementia, Alzheimer's disease and vascular dementia (6805, 2859 and 1544 cases, respectively, and ∼421 241 controls).

Genetic architecture of routinely acquired blood tests in a British South Asian cohort.

Understanding the genetic basis of routinely-acquired blood tests can provide insights into several aspects of human physiology. We report a genome-wide association study of 42 quantitative blood test traits defined using Electronic Healthcare Records (EHRs) of ~50,000 British Bangladeshi and British Pakistani adults. We demonstrate a causal variant within the PIEZO1 locus which was associated with alterations in red cell traits and glycated haemoglobin.

The relationship between ethnicity and multiple sclerosis characteristics in the United Kingdom: A UK MS Register study.

Background: Previous studies have suggested differences in multiple sclerosis (MS) severity according to ethnicity.

Methods: Data were obtained from the UK MS Register, a prospective longitudinal cohort study of persons with MS. We examined the association between self-reported ethnic background and age at onset, symptom of onset and a variety of participant-reported severity measures.

Spinal Cord Stimulation (SCS) reduces Morphine Milligram Equivalents (MME) in patients using Opioid analgesics for Chronic Non-Cancer Pain.

Summary Of Background Data: Chronic Pain is a prevalent condition that affects many people in the United States. Spinal Cord Stimulation (SCS) has been documented to help reduce perceived pain; however, few studies have analyzed the impact of perceived pain on opioid consumption before and after SCS.

Objectives: This retrospective cohort study aimed to evaluate the impact of spinal cord stimulation on opioid consumption after permanent SCS implant.

Adverse Childhood Experiences and Police Contact in Canada.

A growing body of research has demonstrated that adverse childhood experiences (ACEs) are a risk factor for criminal justice system contact. However, much of this research is limited by (1) being conducted in the United States and (2) a lack of details on specific types of harmful experiences of criminal justice system contact, such as police contact characterized by intrusion or harassment. Using survey data from 940 individuals aged 16 to 30 in Canada from the Canadian Study of Adolescent Health Behaviors, this study investigates the relationship between ACEs and police contact, focusing on encounters involving intrusion or harassment.

Factors associated with lack of clinical improvement after vein ablation in the vascular quality initiative.

Background: Insurance companies have adopted variable and inconsistent approval criteria for chronic venous disease (CVD) treatment. Although vein ablation (VA) is accepted as the standard of care for venous ulcers, the treatment criteria for patients with milder forms of CVD remain controversial. This study aims to identify factors associated with a lack of clinical improvement (LCI) in patients with less severe CVD without ulceration undergoing VA to improve patient selection for treatment.

Comparative outcomes of open mesenteric bypass after a failed endovascular or open mesenteric revascularization for chronic mesenteric ischemia.

Introduction: Clinical practice guidelines have recommended an endovascular-first approach (ENDO) for the management of patients with chronic mesenteric ischemia (CMI), whereas an open mesenteric bypass (OMB) is proposed for subjects deemed to be poor ENDO candidates. However, the impact of a previous failed endovascular or open mesenteric reconstruction on a subsequent OMB is unknown. Accordingly, this study was designed to examine the results of a remedial OMB (R-OMB) after a failed ENDO or a primary OMB (P-OMB) for patients with recurrent CMI.

Laser assisted trans-endograft coil embolization of a type II endoleak.

A type II endoleak after endovascular aneurysm repair can be challenging to stop. Numerous methods have been described, including trans-arterial, trans-lumbar, trans-caval, trans-endograft, peri-endograft, and open and laparoscopic surgical techniques. We present our experience with a laser-assisted trans-endograft approach, including technical variations of previous descriptions that might improve efficacy.

Plasma proteomic profiles of UK Biobank participants with multiple sclerosis.

Objective: We aimed to describe plasma protein biomarkers of multiple sclerosis risk and to explore protein biomarkers of disease severity using radiological outcome measures.

Methods: Multiple sclerosis cases and controls were identified in UK Biobank, a longitudinal cohort study of ~500,000 British adults. Plasma proteins were assayed in ~50,000 UK Biobank participants using the Olink proximity extension assay.

Size thresholds for repair of abdominal aortic aneurysms warrant reconsideration.

Background: The historical size threshold for abdominal aortic aneurysm (AAA) repair is widely accepted to be 5.5 cm for men and 5.0 cm for women.

Gene-Environment Interactions for Parkinson's Disease.

Objective: Parkinson's disease (PD) is a neurodegenerative disorder with complex etiology. Multiple genetic and environmental factors have been associated with PD, but most PD risk remains unexplained. The aim of this study was to test for statistical interactions between PD-related genetic and environmental exposures in the 23andMe, Inc.

Genome-wide association study of thyroid-stimulating hormone highlights new genes, pathways and associations with thyroid disease.

Thyroid hormones play a critical role in regulation of multiple physiological functions and thyroid dysfunction is associated with substantial morbidity. Here, we use electronic health records to undertake a genome-wide association study of thyroid-stimulating hormone (TSH) levels, with a total sample size of 247,107. We identify 158 novel genetic associations, more than doubling the number of known associations with TSH, and implicate 112 putative causal genes, of which 76 are not previously implicated.

Functional Disabilities and Food Insufficiency During Pregnancy: Results from the Pregnancy Risk Assessment Monitoring System.

Disability is a well-documented risk factor for food insecurity. However, prior literature has overlooked the possible connection between disability and food insecurity during the antenatal period. This study extends previous research by examining the relationship between those with any functional disabilities and food insufficiency during pregnancy among a sample of mothers.

ADRA2A and IRX1 are putative risk genes for Raynaud's phenomenon.

Raynaud's phenomenon (RP) is a common vasospastic disorder that causes severe pain and ulcers, but despite its high reported heritability, no causal genes have been robustly identified. We conducted a genome-wide association study including 5,147 RP cases and 439,294 controls, based on diagnoses from electronic health records, and identified three unreported genomic regions associated with the risk of RP (p < 5 × 10). We prioritized ADRA2A (rs7090046, odds ratio (OR) per allele: 1.

Genotype Prevalence and Association With Recurrent Myocardial Infarction in British-South Asians Treated With Clopidogrel.

Background: Cytochrome P450 family 2 subfamily C member 19 (CYP2C19) is a hepatic enzyme involved in the metabolism of clopidogrel from a prodrug to its active metabolite. Prior studies of genetic polymorphisms in and their relationship with clinical efficacy have not included South Asian populations.

Objectives: The objective of this study was to assess prevalence of common genotype polymorphisms in a British-South Asian population and correlate these with recurrent myocardial infarction risk in participants prescribed clopidogrel.

Influence of autozygosity on common disease risk across the phenotypic spectrum.

Autozygosity is associated with rare Mendelian disorders and clinically relevant quantitative traits. We investigated associations between the fraction of the genome in runs of homozygosity (F) and common diseases in Genes & Health (n = 23,978 British South Asians), UK Biobank (n = 397,184), and 23andMe. We show that restricting analysis to offspring of first cousins is an effective way of reducing confounding due to social/environmental correlates of F.

Modifiable risk factors for multiple sclerosis have consistent directions of effect across diverse ethnic backgrounds: a nested case-control study in an English population-based cohort.

Background: Multiple sclerosis is a leading cause of non-traumatic neurological disability among young adults worldwide. Prior studies have identified modifiable risk factors for multiple sclerosis in cohorts of White ethnicity, such as infectious mononucleosis, smoking, and obesity during adolescence/early adulthood. It is unknown whether modifiable exposures for multiple sclerosis have a consistent impact on risk across ethnic groups.

Adverse childhood experiences and prescription opioid use during pregnancy: an analysis of the North and South Dakota PRAMS, 2019-2020.

Objectives: This study assesses the association between adverse childhood experiences (ACEs) and prescription opioid use during pregnancy.

Methods: This study uses data on 2,999 individuals from the 2019 and 2020 Pregnancy Risk Assessment Monitoring System (PRAMS) from North Dakota and South Dakota. The relationship between ACEs and prescription opioid use during pregnancy is examined using multiple logistic regression.

Ventriculo-inferior-venacaval shunt salvage via endovascular surgery.

Introduction: Hydrocephalus treatment can be very challenging. While some hydrocephalic patients can be treated endoscopically, many will require ventricular shunting. Frequent shunt issues over a lifetime is not uncommon.