Identification of genetic drivers of plasma lipoprotein size in the Diversity Outbred mouse population.

Despite great progress in understanding lipoprotein physiology, there is still much to be learned about the genetic drivers of lipoprotein abundance, composition, and function. We used ion mobility spectrometry to survey 16 plasma lipoprotein subfractions in 500 Diversity Outbred mice maintained on a Western-style diet. We identified 21 quantitative trait loci (QTL) affecting lipoprotein abundance. To refine the QTL and link them to disease risk in humans, we asked if the human homologs of genes located at each QTL were associated with lipid traits in human genome-wide association studies. Integration of mouse QTL with human genome-wide association studies yielded candidate gene drivers for 18 of the 21 QTL. This approach enabled us to nominate the gene encoding the neutral ceramidase, Asah2, as a novel candidate driver at a QTL on chromosome 19 for large HDL particles (HDL-2b). To experimentally validate Asah2, we surveyed lipoproteins in Asah2-/- mice. Compared to wild-type mice, female Asah2-/- mice showed an increase in several lipoproteins, including HDL. Our results provide insights into the genetic regulation of circulating lipoproteins, as well as mechanisms by which lipoprotein subfractions may affect cardiovascular disease risk in humans.

Lipidomic QTL in Diversity Outbred mice identifies a novel function for α/ß hydrolase domain 2 (Abhd2) as an enzyme that metabolizes phosphatidylcholine and cardiolipin.

We and others have previously shown that genetic association can be used to make causal connections between gene loci and small molecules measured by mass spectrometry in the bloodstream and in tissues. We identified a locus on mouse chromosome 7 where several phospholipids in liver showed strong genetic association to distinct gene loci. In this study, we integrated gene expression data with genetic association data to identify a single gene at the chromosome 7 locus as the driver of the phospholipid phenotypes. The gene encodes α/ß-hydrolase domain 2 (Abhd2), one of 23 members of the ABHD gene family. We validated this observation by measuring lipids in a mouse with a whole-body deletion of Abhd2. The Abhd2KO mice had a significant increase in liver levels of phosphatidylcholine and phosphatidylethanolamine. Unexpectedly, we also found a decrease in two key mitochondrial lipids, cardiolipin and phosphatidylglycerol, in male Abhd2KO mice. These data suggest that Abhd2 plays a role in the synthesis, turnover, or remodeling of liver phospholipids.

Nursing assessments of women with hypertensive disorders during labor in an academic medical center in Mississippi: a best practice implementation project.

OBJECTIVES: The objective of this project was to promote evidence-based practices regarding the nursing assessment of pregnant women with hypertensive disorders admitted to the intrapartum unit. INTRODUCTION: Hypertension during pregnancy has been associated with adverse maternal and fetal outcomes. Ongoing evaluation and nursing care are key in the prevention of complications resulting from hypertensive disorders in pregnancy. METHODS: The implementation of this best practice project was guided by the JBI Model of Evidence-based Healthcare and used the JBI Practical Application of Clinical Evidence System and Getting Research into Practice audit and feedback strategy to promote evidence-based practices regarding the nursing assessment of pregnant women with hypertensive disorders admitted to an intrapartum unit. Eight audit criteria that were representative of best-practice recommendations for nursing assessment of pregnant women with hypertensive disorders were used. A baseline audit was conducted, followed by the implementation of multiple strategies that were determined by the key stakeholders. The project was finalized with a follow-up audit to determine a change in compliance with best-practice recommendations. RESULTS: Baseline audits revealed an average 45% compliance rate with the eight best practice audit criteria. An on-site simulation event, which included a nursing assessment of normal and abnormal lung sounds along with the hands-on practice of deep tendon reflexes, was provided by project members. Evidence-based assessment guidelines were presented and reviewed with all participants. Input from the nursing staff was gathered regarding current documentation practices and electronic health record accessibility. As a result, an electronic health record change was requested, and improvements in nursing practice were observed for five of the eight audit criteria. Follow-up audits revealed an average compliance rate of 73% for all eight audit criteria, a 28% improvement. CONCLUSION: Continuing nursing education and ongoing competency refreshers can affect the quality of client care and outcomes by offering occasions to improve or strengthen clinical expertise and proficiency. For this project, the simulation training event improved nursing staff compliance with best practices.

Lipidomic QTL in Diversity Outbred mice identifies a novel function for α/ß hydrolase domain 2 ( Abhd2 ) as an enzyme that metabolizes phosphatidylcholine and cardiolipin.

We and others have previously shown that genetic association can be used to make causal connections between gene loci and small molecules measured by mass spectrometry in the bloodstream and in tissues. We identified a locus on mouse chromosome 7 where several phospholipids in liver showed strong genetic association to distinct gene loci. In this study, we integrated gene expression data with genetic association data to identify a single gene at the chromosome 7 locus as the driver of the phospholipid phenotypes. The gene encodes α/ß-hydrolase domain 2 ( Abhd2 ), one of 23 members of the ABHD gene family. We validated this observation by measuring lipids in a mouse with a whole-body deletion of Abhd2 . The Abhd2 KO mice had a significant increase in liver levels of phosphatidylcholine and phosphatidylethanolamine. Unexpectedly, we also found a decrease in two key mitochondrial lipids, cardiolipin and phosphatidylglycerol, in male Abhd2 KO mice. These data suggest that Abhd2 plays a role in the synthesis, turnover, or remodeling of liver phospholipids.

Consuming High-Fat and Low-Fat Ground Beef Depresses High-Density and Low-Density Lipoprotein Cholesterol Concentrations, and Reduces Small, Dense Low-Density Lipoprotein Particle Abundance.

We hypothesized that consumption of high-fat (HF) ground beef (24% fat) would not affect plasma concentrations of high-density lipoprotein cholesterol (HDL-C) or low-density lipoprotein (LDL-C), whereas low-fat (LF) ground beef (5% fat) would decrease HDL-C and LDL-C concentrations. In a randomized 2-period crossover, controlled feeding trial, 25 men (mean age and body mass index, 40 years and 31.2) consumed 115-g HF or LF patties, 5/week for 5 weeks with a 4-week washout. The HF treatment increased % energy from fat (p = 0.006) and saturated fat (p = 0.004) and tended (p = 0.060) to depress % energy from carbohydrates. The HF and LF treatments decreased the plasma concentrations of HDL-C (p = 0.001) and LDL-C (p = 0.011). Both ground beef treatments decreased the abundance of HDL3a and increased the abundance of HDL3 (p ≤ 0.003); the LF treatment also decreased the abundance of HDL2b and HDL2a (p ≤ 0.012). The HF and LF treatments decreased the abundance of LDL3 and LDL4 (p ≤ 0.024) and the HF treatment also decreased LDL5 (p = 0.041). Contrary to our hypothesis, the HF treatment decreased plasma HDL-C and LDL-C concentrations despite increased saturated fat intake, and both treatments decreased the abundance of smaller, denser LDL subfractions.

Potential Influencers of COVID-19 Vaccine Acceptance Among Adults Living in the United States Who Have Accepted or Plan to Accept the Vaccine: An Online Survey.

PURPOSE: The purpose of this study was to 1) determine the demographic differences between adults who have accepted, or plan to accept, the COVID-19 vaccine and those who will not accept the COVID-19 vaccine and 2) describe the potential influencers in deciding to accept the COVID-19 vaccine among adults living in the United States who have accepted or plan to accept the vaccine. DESIGN: A cross-sectional design utilizing an online survey was deployed using social media and a crowdsourcing platform. SETTING: United States. SUBJECTS: One thousand three hundred ninety-five (1395) adults completed the survey. The majority were white, male, between the ages of 25 and 45, and with representation from 50 states and Puerto Rico. MEASURES: A two-branched survey was used to assess demographic information, vaccination intention, and 19 potential influencers of COVID-19 vaccine acceptance. ANALYSIS: Analysis included descriptive statistics and Chi-square tests to determine differences between groups. RESULTS: A higher proportion of male (P < .001), married (P < .001), and college-educated (P < .001) participants reported acceptance of the vaccine. The factors with the highest mean score of reported level of influence were duty to protect the vulnerable and contribution to move society back to a sense of normalcy. CONCLUSION: Understanding the potential influencers of vaccine acceptance may provide insight into strategies that could increase vaccination uptake.

Factors contributing to a positive childbirth experience for women in a hospital setting: an umbrella review protocol.

OBJECTIVE: The objective of this umbrella review is to identify and evaluate the factors that contribute to a positive childbirth experience in laboring women in the hospital setting. INTRODUCTION: Childbirth is a milestone for women. Overall, the experience can positively or negatively affect self-esteem, bonding, future childbirth decisions, and overall health and well-being. Understanding of the mother's perception and expectation of the childbirth event is needed to promote positive experiences and outcomes. INCLUSION CRITERIA: This review will consider qualitative systematic reviews that include pregnant women, women in active labor, or women who have recently given birth. This review will consider systematic reviews conducted in a hospital setting in any geographical location reporting on women's positive childbirth experiences, and the factors that led to positive experiences. METHODS: The search strategy will aim to locate qualitative systematic reviews. Databases to be searched include MEDLINE, CINAHL, Embase, Scopus, JBI Evidence Synthesis, and Cochrane Database of Systematic Reviews. Sources of unpublished reviews and gray literature to be searched include ProQuest Dissertations and Theses Sciences and Engineering Collection and OpenGrey. Systematic reviews published since 2001 in the English language will be included. Data will be extracted from systematic reviews by two independent reviewers and findings from the included reviews, as they relate to the umbrella review question, will be presented in tabular format with a supplemental narrative to ensure interpretability. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42021251796.

Whole and Isolated Protein Fractions Differentially Affect Gastrointestinal Integrity Markers in C57Bl/6 Mice Fed Diets with a Moderate-Fat Content.

Various proteins or protein fractions reportedly positively affect gastrointestinal integrity and inflammation in diets providing >45% energy as fat. This study tested whether benefits were seen in diets providing 30% of energy as fat. Purified diets (PD) with isolated soy protein (ISP), dried whole milk powder (DWMP), milk fat globule membrane (MFGM), or milk protein concentrate (MPC) as protein sources were fed to C57BL/6J mice (n = 15/diet group) for 13 weeks. MFGM-fed mice were heaviest (p < 0.005) but remained within breeder norms. Growth rates and gut motility were similar for all PD-fed mice. FITC-dextran assessed gut permeability was lowest in DWMP and MFGM (p = 0.054); overall, plasma endotoxin and unprovoked circulating cytokines indicated a non-inflammatory state for all PD-fed mice. Despite differences in cecal butyrate and intestinal gene expression, all PDs supported gastrointestinal health. Whole milk provided more positive effects compared to its fractions. However, ISP-fed mice showed a >370%, (p < 0.006) increase in colonic myeloperoxidase activity indicative of tissue neutrophil infiltration. Surprisingly, FITC-dextran and endotoxin outcomes were many folds better in PD-fed mice than mice (strain, vendor, age and sex matched) fed a "chow-type" nutritionally adequate non-PD. Additional variables within a diet's matrix appear to affect routine indicators or gastrointestinal health.

Lipoprotein lipase reaches the capillary lumen in chickens despite an apparent absence of GPIHBP1.

In mammals, GPIHBP1 is absolutely essential for transporting lipoprotein lipase (LPL) to the lumen of capillaries, where it hydrolyzes the triglycerides in triglyceride-rich lipoproteins. In all lower vertebrate species (e.g., birds, amphibians, reptiles, fish), a gene for LPL can be found easily, but a gene for GPIHBP1 has never been found. The obvious question is whether the LPL in lower vertebrates is able to reach the capillary lumen. Using purified antibodies against chicken LPL, we showed that LPL is present on capillary endothelial cells of chicken heart and adipose tissue, colocalizing with von Willebrand factor. When the antibodies against chicken LPL were injected intravenously into chickens, they bound to LPL on the luminal surface of capillaries in heart and adipose tissue. LPL was released rapidly from chicken hearts with an infusion of heparin, consistent with LPL being located inside blood vessels. Remarkably, chicken LPL bound in a specific fashion to mammalian GPIHBP1. However, we could not identify a gene for GPIHBP1 in the chicken genome, nor could we identify a transcript for GPIHBP1 in a large chicken RNA-seq data set. We conclude that LPL reaches the capillary lumen in chickens - as it does in mammals - despite an apparent absence of GPIHBP1.

Phenamil, an amiloride derivative, restricts long bone growth and alters keeled-sternum bone architecture in growing chickens.

"Broiler-type" chickens are fast-grow-ing, heavy-bodied birds with high demands on bone quality. Phenamil increased mineralization in cultured murine mesenchymal stem cells. Phenamil effects were tested in 2 groups of weight and gender matched day-old broiler chickens (n = 13). Oral administration of 30 mg phenamil/kg body weight d 1 to 13 reduced growth of chicks d 5 to 14 (P = 0.002); with phenamil-treated (PT) chick body weight being 84% of vehicle-treated (VT) chicks' body weight on d 14. Tissues collected on d 15 showed that femur lengths and widths did not differ, but tibias from PT chicks were 6% shorter (P = 0.002) and 13% narrower (P = 0.012) with 18% thinner tibial cross-sections (P < 0.008) than in VT chicks. Angles of the caudal aspect of the anterior surface of keeled-sternums were 166° in PT chicks, flatter than the 148° found in VT chicks (P = 0.000). Total mineral content of both tibia and femur were lower in PT chicks (P = 0.005 for both). Bone Ca, P, and Mg (ppm) in ash were similar, but Ca:P was lower (1.70 vs 1.75) in PT versus VT chicks (P < 0.05). Osteocalcin was ∼20% lower (P = 0.020), PINP was ∼45% higher (P = 0.000) in PT chicks. Carboxy-terminal telopeptide type I collagen (ICTP) and cross-linked N-telopeptide of type I collagen (NTX1) were similar in the 2 groups. Phenamil had unexpected and detrimental effects on bone formation in growing broiler chicks, reducing linear skeletal growth and markedly changing bone architecture.