Placental and immune cell DNA methylation reference panel for bulk tissue cell composition estimation in epidemiological studies.

To distinguish DNA methylation (DNAm) from cell proportion changes in whole placental villous tissue research, we developed a robust cell type-specific DNAm reference to estimate cell composition. We collated new and existing cell type DNAm profiles quantified via Illumina EPIC or 450k microarrays. To estimate cell composition, we deconvoluted whole placental samples ( = 36) with robust partial correlation based on the top 30 hyper- and hypomethylated sites identified per cell type.

Relationship between alcohol consumption and dementia with Mendelian randomization approaches among older adults in the United States.

Introduction: In observational studies, the association between alcohol consumption and dementia is mixed.

Methods: We performed two-sample Mendelian randomization (MR) using summary statistics from genome-wide association studies of weekly alcohol consumption and late-onset Alzheimer's disease and one-sample MR in the Health and Retirement Study (HRS), wave 2012. Inverse variance weighted two-stage regression provided odds ratios of association between alcohol exposure and dementia or cognitively impaired, non-dementia relative to cognitively normal.

Placental and Immune Cell DNA Methylation Reference Panel for Bulk Tissue Cell Composition Estimation in Epidemiological Studies.

To distinguish DNA methylation (DNAm) from cell proportion changes in whole placental tissue research, we developed a robust cell type-specific DNAm reference to estimate cell composition. We collated newly collected and existing cell type DNAm profiles quantified via Illumina EPIC or 450k microarrays. To estimate cell composition, we deconvoluted whole placental samples (n=36) with robust partial correlation based on the top 50 hyper- and hypomethylated sites per cell type.

Relationship between alcohol consumption and dementia with Mendelian randomization approaches among older adults in the United States.

Background: In observational studies, the association between alcohol consumption and dementia is mixed.

Methods: We performed two-sample Mendelian randomization (MR) using summary statistics from genome-wide association studies of weekly alcohol consumption and late-onset Alzheimer's disease and one-sample MR in the Health and Retirement Study (HRS), wave 2012. Inverse variance weighted two-stage regression provided odds ratios of association between alcohol exposure and dementia or cognitively impaired, non-dementia relative to cognitively normal.

Placental single cell transcriptomics: Opportunities for endocrine disrupting chemical toxicology.

The placenta performs essential biologic functions for fetal development throughout pregnancy. Placental dysfunction is at the root of multiple adverse birth outcomes such as intrauterine growth restriction, preeclampsia, and preterm birth. Exposure to endocrine disrupting chemicals during pregnancy can cause placental dysfunction, and many prior human studies have examined molecular changes in bulk placental tissues.

Practical approaches to the detection of macrotroponin.

Introduction: Macrotroponin is increasingly recognised as a cause of confusion in interpreting high-sensitivity cardiac troponin (hs-cTnI) results. In this study, we sought to evaluate two practical approaches to detecting macrotroponin. These two approaches are PEG precipitation and SVM (support vector machine) analysis to classify discrepancies between hs-cTn assays.

Detrimental effects of PCSK9 loss-of-function in the pediatric host response to sepsis are mediated through independent influence on Angiopoietin-1.

Background: Sepsis is associated with significant mortality. Yet, there are no efficacious therapies beyond antibiotics. PCSK9 loss-of-function (LOF) and inhibition, through enhanced low-density lipoprotein receptor (LDLR) mediated endotoxin clearance, holds promise as a potential therapeutic approach among adults.

Placental cell type deconvolution reveals that cell proportions drive preeclampsia gene expression differences.

The placenta mediates adverse pregnancy outcomes, including preeclampsia, which is characterized by gestational hypertension and proteinuria. Placental cell type heterogeneity in preeclampsia is not well-understood and limits mechanistic interpretation of bulk gene expression measures. We generated single-cell RNA-sequencing samples for integration with existing data to create the largest deconvolution reference of 19 fetal and 8 maternal cell types from placental villous tissue (n = 9 biological replicates) at term (n = 40,494 cells).

Detrimental effects of PCSK9 loss-of-function in the pediatric host response to sepsis are mediated through independent influence on Angiopoietin-1.

Sepsis is associated with significant mortality, yet there are no efficacious therapies beyond antibiotics and supportive care. In adult sepsis studies, PCSK9 loss-of-function (LOF) and inhibition has shown therapeutic promise, likely through enhanced low-density lipoprotein receptor (LDLR) mediated endotoxin clearance. In contrast, we previously demonstrated higher mortality in septic juvenile hosts with LOF.

Smad3 promotes adverse cardiovascular remodeling and dysfunction in doxorubicin-treated hearts.

Many anticancer therapies cause serious cardiovascular complications that degrade quality of life and cause early mortality in treated patients. Specifically, doxorubicin is known as an effective anticancer agent that causes cardiomyopathy in treated patients. There has been growing interest in defining the role of endothelial cells in cardiac damage by doxorubicin.

Effect of Macrotroponin in a Cohort of Community Patients with Elevated Cardiac Troponin.

Background: Macrotroponin is an important cause of discrepancy between current high-sensitivity cardiac troponin (hs-cTn) assays, however, its clinical significance is unclear. This study examined the effects of macrotroponin and repeat testing by different hs-cTnI assays in a cohort of community patients with elevated hs-cTnI.

Methods: The first residual serum specimen from each patient in the community admitted to hospital with elevated hs-cTnI (Siemens hs-cTnI Centaur) was retested after immunoglobulin depletion and by 5 other hs-cTn assays.

Assessment of International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) Code Assignment Validity for Case Finding of Medication-related Hypoglycemia Acute Care Visits Among Medicare Beneficiaries.

Objective: Administrative claims are commonly relied upon to identify hypoglycemia. We assessed validity of 14 International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis code assignments to identify medication-related hypoglycemia leading to acute care encounters.

Research Design And Methods: A multisite, retrospective medical record review study was conducted in a sample of Medicare beneficiaries prescribed outpatient diabetes medications and who received hospital care between January 1, 2016 and September 30, 2017.

Actions to improve quality: results from a national hospital survey.

Objectives: CMS measures and reports hospital performance to drive quality improvement (QI), but information on actions that hospitals have taken in response to quality measurement is lacking. We aimed to develop national estimates of QI actions undertaken by hospitals and to explore their relationship to performance on CMS quality measures.

Study Design: Nationally representative cross-sectional survey of acute care hospitals in 2016 (n = 1313 respondents; 64% response rate).

Identification of macrotroponin T: findings from a case report and non-reproducible troponin T results.

Objectives: Macrotroponin is due to cardiac troponin (cTn) binding to endogenous cTn autoantibodies. While previous studies showed a high incidence of macrotroponin affecting cTnI assays, reports of macrotroponin T, particularly without cTnI reactivity, have been rare. Although the clinical significance of macrotroponin is not fully understood, macroenzymes and complexes are recognised to cause confusion in interpretation of laboratory results.

Home health agency adoption of quality improvement activities and association with performance.

Background: The Centers for Medicare & Medicaid Services (CMS) Home Health Quality Reporting Program (HHQRP) uses performance measurement to spur improvements in home health agencies' (HHAs') quality of care. We examined quality improvement (QI) activities HHAs reported making to improve on HHQRP quality measures, and whether reported QI activities were associated with better measure performance.

Methods: We used responses (N = 1052) from a Web- and mail-based survey of a stratified random sample of HHAs included in CMS Home Health Compare in October 2019.

Excess death estimates in patients with end-stage renal disease - United States, February-August 2020.

This article describes an estimated 6953–10 316 excess deaths among individuals with end-stage renal disease during the early months of the COVID-19 pandemic in February 2020–August 2020 (compared to death rates prior to the pandemic). Notably, the estimated number of excess deaths was reported as 10.8–16.

Effect of macrotroponin on the utility of cardiac troponin I as a prognostic biomarker for long term total and cardiovascular disease mortality.

Macrotroponin is a complex formed between endogenous cardiac troponin autoantibodies and circulating cardiac troponin (cTn). It is a recognised cause of discrepancy between current high sensitivity troponin (hs-cTn) assays; and immunoglobulin-bound (macrotroponin) and unbound cTn can coexist in varying proportions in the acute setting. Increasingly it is considered when laboratory cTn results do not match a patient's clinical picture.

The impact of a national COVID-19 lockdown on acute coronary syndrome hospitalisations in New Zealand (ANZACS-QI 55).

Background: Countries with a high incidence of coronavirus 2019 (COVID-19) reported reduced hospitalisations for acute coronary syndromes (ACS) during the pandemic. This study describes the impact of a nationwide lockdown on ACS hospitalisations in New Zealand (NZ), a country with a low incidence of COVID-19.

Methods: All patients admitted to a NZ Hospital with ACS who underwent coronary angiography in the All NZ ACS Quality Improvement registry during the lockdown (23 March - 26 April 2020) were compared with equivalent weeks in 2015-2019.

Excess Death Estimates in Patients with End-Stage Renal Disease - United States, February-August 2020.

End-stage renal disease (ESRD) is a condition in which kidney function has permanently declined such that renal replacement therapy* is required to sustain life (1). The mortality rate for patients with ESRD in the United States has been declining since 2001 (2). However, during the COVID-19 pandemic, ESRD patients are at high risk for COVID-19-associated morbidity and mortality, which is due, in part, to weakened immune systems and presence of multiple comorbidities (3-5).

Prenatal exposure to metals and autism spectrum disorder: Current status and future directions.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder with genetic and environmental contributors to etiology. Many metals have the potential to be neurotoxic and their exposures are widespread. The field of metals exposure and ASD research is emerging, and in this review article we assess the current state of the literature, with emphasis on the previous two years.

A three-way comparison of glycated haemoglobin: are results from the three platforms interchangeable?

Aims: To determine whether glycated haemoglobin (HbA1c) results from three commonly used platforms can be interpreted cumulatively and used interchangeably in individuals with common haemoglobinopathies. A secondary goal was to assess the relationship between HbA1c concentrations, and haemoglobin and mean corpuscular volume in this population.

Methods: One hundred and forty-five samples, mostly with haemoglobinopathies, were tested by each of: Roche Gen.

Change in troponin concentrations in patients with macrotroponin: An in vitro mixing study.

Introduction: Macrotroponin is a complex formed between endogenous cardiac troponin autoantibodies (cTnAABs) and circulating cardiac troponin (cTn). The potential effect of macrotroponin on current high sensitivity cTn assays has not been fully explored but has recently been identified as a major cause of discrepancy in cTn results between assays. In this study we investigated the effects of mixing troponin (cTn) standards to specimens with and without macrotroponin.

Cell Types in Environmental Epigenetic Studies: Biological and Epidemiological Frameworks.

Purpose Of Review: This article introduces the roles of perinatal DNA methylation in human health and disease, highlights the challenges of tissue and cellular heterogeneity to studying DNA methylation, summarizes approaches to overcome these challenges, and offers recommendations in conducting research in environmental epigenetics.

Recent Findings: Epigenetic modifications are essential for human development and are labile to environmental influences, especially during gestation. Epigenetic dysregulation is also a hallmark of multiple diseases.