Curation and validation of electronic medical record-based dementia diagnoses in the VA Million Veteran Program.

Background: The age distribution and diversity of the VA Million Veteran Program (MVP) cohort make it a valuable resource for studying the genetics of Alzheimer's disease (AD) and related dementias (ADRD).

Objective: We present and evaluate the performance of several International Classification of Diseases (ICD) code-based classification algorithms for AD, ADRD, and dementia for use in MVP genetic studies and other studies using VA electronic medical record (EMR) data. These were benchmarked relative to existing ICD algorithms and AD-medication-identified cases.

Multidisciplinary Management of Morbidities Associated with Chronic Graft-Versus-Host Disease.

Chronic graft-versus-host disease (cGVHD) represents a common long-term complication after allogeneic hematopoietic stem cell transplantation (HSCT). It imposes a significant morbidity burden and is the leading cause of non-relapse mortality among long-term HSCT survivors. cGVHD can manifest in nearly any organ, severely affecting the quality of life of a transplant survivor.

Genomic structural equation modeling reveals latent phenotypes in the human cortex with distinct genetic architecture.

Genetic contributions to human cortical structure manifest pervasive pleiotropy. This pleiotropy may be harnessed to identify unique genetically-informed parcellations of the cortex that are neurobiologically distinct from functional, cytoarchitectural, or other cortical parcellation schemes. We investigated genetic pleiotropy by applying genomic structural equation modeling (SEM) to map the genetic architecture of cortical surface area (SA) and cortical thickness (CT) for 34 brain regions recently reported in the ENIGMA cortical GWAS.

Sexual health and emotional wellbeing of patients with haematological malignancies: general review.

Sexual health is an important aspect of a person's life. Many patients and haematologists believe that intimacy and sexuality issues are substantial during cancer treatment. The haematological cancer disease, diagnosis, shock of the announcement, treatment, and follow-up appointments, can all have negative effects on the quality of life of patients, their partners, other family members, and friends.

Role of the X Chromosome in Alzheimer Disease Genetics.

Importance: The X chromosome has remained enigmatic in Alzheimer disease (AD), yet it makes up 5% of the genome and carries a high proportion of genes expressed in the brain, making it particularly appealing as a potential source of unexplored genetic variation in AD.

Objectives: To perform the first large-scale X chromosome-wide association study (XWAS) of AD.

Design, Setting, And Participants: This was a meta-analysis of genetic association studies in case-control, family-based, population-based, and longitudinal AD-related cohorts from the US Alzheimer's Disease Genetics Consortium, the Alzheimer's Disease Sequencing Project, the UK Biobank, the Finnish health registry, and the US Million Veterans Program.

No Replication of Alzheimer's Disease Genetics as a Moderator of Combat Exposure's Association with PTSD risk in 138,592 Combat Veterans.

Large-scale cohort and epidemiological studies suggest that posttraumatic stress disorder (PTSD) confers risk for late-onset Alzheimer's disease (AD) and related dementias (ADRD); however, the basis for this association remains unclear. Several prior studies of military Veterans have reported that carriers of the apolipoprotein E () ε4 gene variant are at heightened risk for the development of PTSD following combat exposure, suggesting that PTSD and ADRD may share some genetic risk. This cohort study was designed to further examine the hypothesis that ADRD genetic risk also confers risk for PTSD.

Traumatic Brain Injury and Genetic Risk for Alzheimer's Disease Impact Cerebrospinal Fluid β-Amyloid Levels in Vietnam War Veterans.

Traumatic brain injuries (TBIs) may increase the risk for Alzheimer's disease (AD) and its neuropathological correlates, although the mechanisms of this relationship are unclear. The current study examined the synergistic effects of TBI and genetic risk for AD on β-amyloid (Aβ) levels among Vietnam War Veterans. We hypothesized that the combination of TBI and higher polygenic risk score (PRS) for AD would be associated with lower cerebrospinal fluid (CSF) Aβ.

Subjective cognitive concerns, APOE ε4, PTSD symptoms, and risk for dementia among older veterans.

Background: Posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) are associated with self-reported problems with cognition as well as risk for Alzheimer's disease and related dementias (ADRD). Overlapping symptom profiles observed in cognitive disorders, psychiatric disorders, and environmental exposures (e.g.

Systems biology dissection of PTSD and MDD across brain regions, cell types, and blood.

The molecular pathology of stress-related disorders remains elusive. Our brain multiregion, multiomic study of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) included the central nucleus of the amygdala, hippocampal dentate gyrus, and medial prefrontal cortex (mPFC). Genes and exons within the mPFC carried most disease signals replicated across two independent cohorts.

The Role of X Chromosome in Alzheimer's Disease Genetics.

Importance: The X chromosome has remained enigmatic in Alzheimer's disease (AD), yet it makes up 5% of the genome and carries a high proportion of genes expressed in the brain, making it particularly appealing as a potential source of unexplored genetic variation in AD.

Objectives: Perform the first large-scale X chromosome-wide association study (XWAS) of AD. Primary analyses are non-stratified, while secondary analyses evaluate sex-stratified effects.

Less is more: Smaller hippocampal subfield volumes predict greater improvements in posttraumatic stress disorder symptoms over 2 years.

Posttraumatic stress disorder (PTSD) is a heterogeneous disorder, and symptom severity varies over time. Neurobiological factors that predict PTSD symptoms and their chronicity remain unclear. This study investigated whether the volume of the hippocampus and its subfields, particularly cornu ammonis (CA) 1, CA3, and dentate gyrus, are associated with current PTSD symptoms and whether they predict PTSD symptom changes over 2 years.

Complete genome sequences of seven phages Albedo, Kenzers, Swervy, Cranjis, JaimeB, Fullmetal, and Stormbreaker.

Seven bacteriophages were isolated from soil in Pennsylvania and Wisconsin using the host . These bacteriophages range in the number of predicted genes encoded, from 25 to 91, and are distributed across actinobacteriophage clusters EB, EC, EE, and EK.

An EWAS of dementia biomarkers and their associations with age, African ancestry, and PTSD.

Background: Large-scale cohort and epidemiological studies suggest that PTSD confers risk for dementia in later life but the biological mechanisms underlying this association remain unknown. This study examined this question by assessing the influences of PTSD, APOE ε4 genotypes, DNA methylation, and other variables on the age- and dementia-associated biomarkers Aβ40, Aβ42, GFAP, NfL, and pTau-181 measured in plasma. Our primary hypothesis was that PTSD would be associated with elevated levels of these markers.

Blood-based DNA methylation and exposure risk scores predict PTSD with high accuracy in military and civilian cohorts.

Background: Incorporating genomic data into risk prediction has become an increasingly useful approach for rapid identification of individuals most at risk for complex disorders such as PTSD. Our goal was to develop and validate Methylation Risk Scores (MRS) using machine learning to distinguish individuals who have PTSD from those who do not.

Methods: Elastic Net was used to develop three risk score models using a discovery dataset (n = 1226; 314 cases, 912 controls) comprised of 5 diverse cohorts with available blood-derived DNA methylation (DNAm) measured on the Illumina Epic BeadChip.

Pharmacists' perspectives on recommending herbal medicines for acute infections: a qualitative study.

Background: Community pharmacists have an essential role in antimicrobial stewardship by providing self-care advice for self-limiting infections.

Aim: To explore community pharmacists' perceptions and experiences of advising patients on management of acute respiratory tract infections (RTIs) and urinary tract infections (UTIs), and to explore issues regarding use of over-the-counter (OTC) medicines, including herbal medicines.

Design & Setting: A qualitative study using semi-structured interviews with community pharmacists in England.

Dental Caries, Race and Incident Ischemic Stroke, Coronary Heart Disease, and Death.

Background: Dental caries is a highly prevalent disease worldwide. In the United States, untreated dental caries is present in >1 in 5 adults. The objective of this study was to determine the relationship between dental caries and incident ischemic stroke, coronary heart disease (CHD) events, and death.

Longitudinal study of traumatic-stress related cellular and cognitive aging.

Traumatic stress is associated with both accelerated epigenetic age and increased risk for dementia. Accelerated epigenetic age might link symptoms of traumatic stress to dementia-associated biomarkers, such as amyloid-beta (Aβ) proteins, neurofilament light (NFL), and inflammatory molecules. We tested this hypothesis using longitudinal data obtained from 214 trauma-exposed military veterans (85 % male, mean age at baseline: 53 years, 75 % White) who were assessed twice over the course of an average of 5.

PTSD and Alcohol Use Disorders Predict the Pace of Cellular Aging.

Advanced epigenetic age is associated with psychopathology and may help to explain the link between psychopathology and physical health morbidity and mortality. Using a longitudinal sample of 171 trauma-exposed Veterans, we modeled the rate of change in epigenetic age across two time points (averaging 5.58 years apart) using two epigenetic age algorithms (GrimAge and Horvath) and tested associations with posttraumatic stress disorder (PTSD), alcohol use disorder (AUD), and depression.

Genome-wide association study of traumatic brain injury in U.S. military veterans enrolled in the VA million veteran program.

Large-scale genetic studies of traumatic brain injury (TBI) are lacking; thus, our understanding of the influence of genetic factors on TBI risk and recovery is incomplete. This study aimed to conduct a genome-wide association study (GWAS) of TBI in VA Million Veteran Program (MVP) enrollees. Participants included a multi-ancestry cohort (European, African, and Hispanic ancestries; N = 304,485; 111,494 TBI cases, 192,991 controls).