Non-APOE variants predominately expressed in smooth muscle cells contribute to the influence of Alzheimer's disease genetic risk on white matter hyperintensities.

Introduction: White matter hyperintensity volumes (WMHVs) are disproportionally prevalent in individuals with Alzheimer's disease (AD), potentially reflecting neurovascular injury. We quantify the association between AD polygenic risk score (AD-PRS) and WMHV, exploring single-nucleotide polymorphisms (SNPs) that are proximal to genes overexpressed in cerebrovascular cell species.

Methods: In a UK-Biobank sub-sample (mean age = 64, range = 45-81 years), we associate WMHV with (1) AD-PRS estimated via SNPs across the genome (minus apolipoprotein E [APOE] locus) and (2) AD-PRS estimated with SNPs proximal to specific genes that are overexpressed in cerebrovascular cell species.

Proof-of-concept recall-by-genotype study of extremely low and high Alzheimer's polygenic risk reveals autobiographical deficits and cingulate cortex correlates.

Background: Genome-wide association studies demonstrate that Alzheimer's disease (AD) has a highly polygenic architecture, where thousands of independent genetic variants explain risk with high classification accuracy. This AD polygenic risk score (AD-PRS) has been previously linked to preclinical cognitive and neuroimaging features observed in asymptomatic individuals. However, shared variance between AD-PRS and neurocognitive features are small, suggesting limited preclinical utility.

Reduced brain oxygen metabolism in patients with multiple sclerosis: Evidence from dual-calibrated functional MRI.

Cerebral energy deficiency is increasingly recognised as an important feature of multiple sclerosis (MS). Until now, we have lacked non-invasive imaging methods to quantify energy utilisation and mitochondrial function in the human brain. Here, we used novel dual-calibrated functional magnetic resonance imaging (dc-fMRI) to map grey-matter (GM) deoxy-haemoglobin sensitive cerebral blood volume (CBV), cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen consumption (CMRO) in patients with MS (PwMS) and age/sex matched controls.

Alzheimer's genetic risk effects on cerebral blood flow across the lifespan are proximal to gene expression.

Cerebrovascular dysregulation such as altered cerebral blood flow (CBF) can be observed in Alzheimer's disease (AD) and may precede symptom onset. Genome wide association studies show that AD has a polygenic aetiology, providing a tool for studying AD susceptibility across the lifespan. Here, we ascertain whether the AD genetic risk effects on CBF previously observed (Chandler et al.

A flow-diffusion model of oxygen transport for quantitative mapping of cerebral metabolic rate of oxygen (CMRO) with single gas calibrated fMRI.

One promising approach for mapping CMRO is dual-calibrated functional MRI (dc-fMRI). This method exploits the Fick Principle to combine estimates of CBF from ASL, and OEF derived from BOLD-ASL measurements during arterial O and CO modulations. Multiple gas modulations are required to decouple OEF and deoxyhemoglobin-sensitive blood volume.

Parent/Caregiver Views of the Effectiveness of Speech-Language Pathology for Children Born With Cleft Palate Delivered via Telemedicine During COVID-19.

Purpose: The purpose of this study was to describe and examine parent views of speech-language pathology (SLP) for children born with cleft palate delivered via telemedicine during the COVID-19 pandemic in the United Kingdom (UK).

Method: Parents were asked whether they found this method of delivery "very effective," "somewhat effective," or "not at all effective." Free text was then invited.

Corrigendum: A Frequency-Domain Machine Learning Method for Dual-Calibrated fMRI Mapping of Oxygen Extraction Fraction (OEF) and Cerebral Metabolic Rate of Oxygen Consumption (CMRO).

[This corrects the article DOI: 10.3389/frai.2020.

Tiagabine induced modulation of oscillatory connectivity and activity match PET-derived, canonical GABA-A receptor distributions.

As the most abundant inhibitory neurotransmitter in the mammalian brain, γ-aminobutyric acid (GABA) plays a crucial role in shaping the frequency and amplitude of oscillations, which suggests a role for GABA in shaping the topography of functional connectivity and activity. This study explored the effects of pharmacologically blocking the reuptake of GABA (increasing local concentrations) using the GABA transporter 1 (GAT1) blocker, tiagabine (15 mg). In a placebo-controlled crossover design, we collected resting magnetoencephalography (MEG) recordings from 15 healthy individuals prior to, and at 1-, 3- and 5- hours post, administration of tiagabine and placebo.

Multimodal hippocampal and amygdala subfield volumetry in polygenic risk for Alzheimer's disease.

Preclinical models of Alzheimer's disease (AD) suggest that volumetric reductions in medial temporal lobe (MTL) structures manifest before clinical onset. AD polygenic risk scores (PRSs) are further linked to reduced MTL volumes (the hippocampus/amygdala); however, the relationship between the PRS and specific subregions remains unclear. We determine the relationship between the AD-PRSs and MTL subregions in a large sample of young participants (N = 730, aged 22-35 years) using a multimodal (T1w/T2w) approach.

A frequency-domain machine learning method for dual-calibrated fMRI mapping of oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO).

Magnetic resonance imaging (MRI) offers the possibility to non-invasively map the brain's metabolic oxygen consumption (CMRO), which is essential for understanding and monitoring neural function in both health and disease. However, in depth study of oxygen metabolism with MRI has so far been hindered by the lack of robust methods. One MRI method of mapping CMRO is based on the simultaneous acquisition of cerebral blood flow (CBF) and blood oxygen level dependent (BOLD) weighted images during respiratory modulation of both oxygen and carbon dioxide.

Polygenic risk for Alzheimer's disease shapes hippocampal scene-selectivity.

Preclinical models of Alzheimer's disease (AD) suggest APOE modulates brain function in structures vulnerable to AD pathophysiology. However, genome-wide association studies now demonstrate that AD risk is shaped by a broader polygenic architecture, estimated via polygenic risk scoring (AD-PRS). Despite this breakthrough, the effect of AD-PRS on brain function in young individuals remains unknown.

"What's happening in Syria even affects the rocks": a qualitative study of the Syrian refugee experience accessing noncommunicable disease services in Jordan.

Background: Humanitarian actors and host-countries in the Middle East and North Africa region are challenged with meeting the health needs of Syrian refugees and adjusting the response to contemporary humanitarian conditions - urban-based refugees, stressed host-country health systems and high NCD prevalence. Although several studies have explored NCD prevalence, utilization of services and barriers to access, these analyses took place prior to dramatic shifts in Jordanian health policy and did not account for nuances in health seeking and utilization behaviors or operational barriers. Accordingly, we aimed to understand the depth and nuances of Syrian refugees' experiences accessing NCD services in urban and semi-urban settings in Jordan.

Polygenic impact of common genetic risk loci for Alzheimer's disease on cerebral blood flow in young individuals.

Genome-wide association studies (GWAS) show that many common alleles confer risk for developing Alzheimer's disease (AD). These risk loci may contribute to MRI alterations in young individuals, preceding the clinical manifestations of AD. Prior evidence identifies vascular dysregulation as the earliest marker of disease progression.

Recommendations on How to Manage Anticipated Communication Dilemmas Involving Medical Countermeasures in an Emergency.

National investments to facilitate prompt access to safe and effective medical countermeasures (MCMs) (ie, products used to diagnose, prevent, protect from, or treat conditions associated with chemical, biological, radiological, or nuclear threats, or emerging infectious diseases) have little merit if people are not willing to take a recommended MCM during an emergency or inadvertently misuse or miss out on a recommended MCM during an emergency. Informed by the Expert Working Group on MCM Emergency Communication, the Johns Hopkins Center for Health Security developed recommendations for achieving desired public health outcomes through improved MCM communication based on a review of model practices in risk communication, crisis communication, and public warnings; detailed analysis of recent health crises involving MCMs; and development of a scenario depicting future MCM communication dilemmas. The public's topics of concern, emotional requirements, capacity for processing information, and health needs will evolve as an emergency unfolds, from a pre-event period of routine conditions, to a crisis state, to a post-event period of reflection.

Public Health Resilience Checklist for High-Consequence Infectious Diseases-Informed by the Domestic Ebola Response in the United States.

Context: The experiences of communities that responded to confirmed cases of Ebola virus disease in the United States provide a rare opportunity for collective learning to improve resilience to future high-consequence infectious disease events.

Design: Key informant interviews (n = 73) were conducted between February and November 2016 with individuals who participated in Ebola virus disease planning or response in Atlanta, Georgia; Dallas, Texas; New York, New York; or Omaha, Nebraska; or had direct knowledge of response activities. Participants represented health care; local, state, and federal public health; law; local and state emergency management; academia; local and national media; individuals affected by the response; and local and state governments.

Lessons from the domestic Ebola response: Improving health care system resilience to high consequence infectious diseases.

Background: The domestic response to the West Africa Ebola virus disease (EVD) epidemic from 2014-2016 provides a unique opportunity to distill lessons learned about health sector planning and operations from those individuals directly involved. This research project aimed to identify and integrate these lessons into an actionable checklist that can improve health sector resilience to future high-consequence infectious disease (HCID) events.

Methods: Interviews (N = 73) were completed with individuals involved in the domestic EVD response in 4 cities (Atlanta, Dallas, New York, and Omaha), and included individuals who worked in academia, emergency management, government, health care, law, media, and public health during the response.

Being prepared: emergency treatment following a nerve agent release.

Nerve agents are extremely toxic and are some of the most lethal substances on earth. This group of chemicals consists of sarin, cyclosarin, soman, tabun, VX, and VR. It is currently unknown how many countries possess these chemicals and in what quantities.