Haptoglobin genotype is a risk factor for coronary artery disease in prediabetes: A case-control study.

Objective: Coronary artery disease (CAD) prediction remains inconsistent with many unappreciated risk factors. Haptoglobin genotype determines the haptoglobin protein's effectiveness to bind free hemoglobin and prevent oxidative stress, a contributor to atherosclerosis. The haptoglobin 2-2 genotype increases the prevalence of cardiovascular disease (CVD) approximately five times compared to the 1-1 genotype in individuals with diabetes. The risk is unknown in prediabetes. The purpose of this study was to determine an association between haptoglobin genotype and CAD in prediabetes. Methods: The researchers used case-control convenience sampling from two cardiovascular disease prevention clinics in Memphis, TN, and Spokane, WA, from January 1, 2016 to March 31, 2020. Participants were ages 35-70, had prediabetes, and free of chronic inflammatory or infectious diseases. Cases had a history of subclinical or clinical CAD, while controls did not have a history of CAD. Differences between cases and controls and among haptoglobin genotypes were analyzed using t-tests and ANOVA for continuous variables and chi-square or Fisher's exact tests for categorical variables. Associations among Hp genotypes and CAD were estimated using logistic regression. Results: The sample (N = 178; 72 cases and 106 controls) was 96 % white and 64 % male. Cases had lower total cholesterol (p = 0.0001) and high-sensitivity C-reactive protein (p = 0.021). Except for CAD, haptoglobin genotype was independent of any demographic or clinical variable. Haptoglobin 2-2 genotype had 4.0 times higher odds of CAD than haptoglobin 1-1 (p = 0.01). Conclusion: Haptoglobin 2-2 genotype had approximately four times higher odds of having CAD compared to the haptoglobin 1-1 genotype. Cases had more desirable clinical profiles, likely attributable to more aggressive treatment of traditional risk factors than controls. Haptoglobin genotype is a potentially important CAD risk factor in prediabetes (88 million Americans). Further studies are needed for interventions to reduce the oxidative stress associated with the Hp 2-2 genotype and glycosylated hemoglobin and for CAD reduction.

Oxidative Stress Underpins Clinical, Social, and Genetic Risk Factors for Atherosclerotic Cardiovascular Disease.

Background: Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide and is poorly predicted with current risk estimation tools. The biological mechanisms relating ASCVD risk factors to oxidative stress (OS) and how this accumulates ASCVD risk are misunderstood. Purpose: To develop a comprehensive conceptual model explaining how expanded clinical, social, and genetic ASCVD risk factors accumulate ASCVD risk through OS. Conclusions: OS (primarily from excess reactive oxygen species) and inflammation are present along the entire ASCVD pathophysiologic continuum. An expanded list of clinical and social ASCVD risk factors (including hypertension, obesity, diabetes, kidney disease, inflammatory diseases, substance use, poor nutrition, psychosocial stress, air pollution, race, and genetic ancestry) influence ASCVD largely through increased OS. Many risk factors exert a positive feedback mechanism to increase OS. One genetic risk factor, haptoglobin (Hp) genotype, is associated with higher ASCVD risk in diabetes and hypothesized to do the same in those with insulin resistance due to the Hp 2-2 genotype increasing OS. Implications: Understanding the biological mechanisms of OS informs how these ASCVD risk factors relate to each other and compound ASCVD risk. Individualized ASCVD risk estimation should include a comprehensive, holistic perspective of risk factors to better address the clinical, social, and genetic influences of OS. Preventing and reducing OS is key to preventing ASCVD development or progression.

An Integrative Review of the Utilization of the Perceived Stress Scale in Stroke Recovery.

ABSTRACT: BACKGROUND: Stroke survivors (SS) may experience alterations in physical and cognitive processes that increase stress and reduce well-being. Timely and accurate measurement of stress throughout the continuum of recovery is necessary to inform targeted interventions that will improve quality of life for this group. OBJECTIVE: The aim of this study was to describe the utilization of the Perceived Stress Scale (PSS) during recovery in SS. METHODS: A comprehensive literature search was conducted using CINAHL, PsycINFO, PubMed, and Scopus databases. Studies were included if they captured primary data collection using any version of the PSS at any time point in the poststroke recovery period and were published in English between 2011 and 2022. Systematic reviews and meta-analyses were excluded. Evidence was synthesized, and themes were discussed. RESULTS: Among 397 studies, a total of 13 met inclusion criteria. Of these, 8 were cross-sectional studies, 3 were longitudinal studies, 1 was a randomized controlled trial, and the remaining study was a prospective nonrandomized trial. The PSS-10 (n = 7, 54%) was the most used version of the instrument, followed by the PSS-14 (n = 3, 23%) and PSS-4 (n = 2, 15.4%), with the modified PSS-10 being used in only 1 (7.6%) study. The PSS surveys were administered at various time points, ranging from the first day of admission to 3, 6, 9, or 12 months after discharge. Perceived stress may continue to negatively influence SS's psychological and physical well-being throughout the chronic phase of recovery. CONCLUSIONS: Stress is a unique and individualized experience that influences recovery trajectories in SS, an experience often overlooked or marginalized by clinicians and healthcare providers. To help mobilize strategies to achieve long-term health and wellness goals, future studies should explore and tailor interventions to minimize the influence of stress, as identified by the PSS, on well-being and quality of life during poststroke recovery.

Impact of Social Determinants of Health on Outcomes Following Resection for Hepatocellular Carcinoma.

BACKGROUND: We sought to determine the impact of social determinants of health (SDoH) on outcomes of patients undergoing resection for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Patients with HCC in the National Cancer Database who underwent resection from 2009 to 2018 were identified. SDoH associated with length of stay (LOS), 30-day readmission, and 30-day mortality were analyzed using regression analyses adjusted for confounding variables. RESULTS: Among 9235 patients, the median age (range) was 65.0 (18-90) years, 72.1% were male, and 57.9% were White. A total of 3% were uninsured, 11.1% had Medicaid, 21% resided in regions with a median household income within the lowest quartile of the US population, and 27.0% resided in regions within the lowest quartile of education level. The odds for having longer LOS were lower among patients with the highest regional education level compared with those with the lowest level [odds ratio (OR) 0.86, 95% confidence interval (CI) 0.77-0.97]. The risk of readmission was lower among patients with Medicare (OR 0.52; 95% CI 0.33-0.81), Medicaid (OR 0.52; 95% CI 0.31-0.87), or private insurance (OR 0.56; 95% CI 0.35-0.88) compared with uninsured patients. Thirty-day overall mortality was less likely among patients with Medicare (OR 0.45; 95% CI 0.27-0.75), Medicaid (OR 0.53; 95% CI 0.30-0.93), or private insurance (OR 0.40; 95% CI 0.24-0.66), and among patients with high regional income (OR 0.58; 95% CI 0.44-0.77). CONCLUSIONS: Adjusted regression analyses identified SDoH that were associated with HCC outcomes. Increased awareness of how SDoH relate to outcomes may inform strategies that attempt to account for these associations and improve patient outcomes.

Verapamil inhibits TXNIP-NLRP3 inflammasome activation and preserves functional recovery after intracerebral hemorrhage in mice.

Intracerebral hemorrhage (ICH) is the second most common type of stroke with no satisfactory treatment. Recent studies from our group and others indicated a potential positive effect of verapamil, a commonly prescribed calcium channel blocker, with thioredoxin-interacting protein (TXNIP) inhibitor properties, in ischemic stroke and cognitive disorders. It is unclear whether there would be a beneficial effect of verapamil administration in ICH. Therefore, this study was designed to determine the neuroprotective effects of verapamil in a murine ICH model. ICH was induced by stereotactic injection of collagenase type VII (0.075 U) into the right striatum of adult male C57BL/6 mice. Verapamil (0.15 mg/kg) or saline was administered intravenously at 1 h post-ICH followed by oral (1 mg/kg/d) administration in drinking water for 28 days. Motor and cognitive function were assessed using established tests for motor coordination, spatial learning, short- and long-term memory. A subset of animals was sacrificed at 72 h after ICH for molecular analysis. Verapamil treatment reduced expression of TXNIP and NOD-like receptor pyrin domain-containing-3 inflammasome activation in the perihematomal area. These protective effects of verapamil were associated with decreased proinflammatory mediators, microglial activation, and blood-brain barrier permeability markers and paralleled less phosphorylated nuclear factor kappa B level. Our findings also demonstrate that long-term low-dose verapamil effectively attenuated motor and cognitive impairments. Taken together, these data indicate that verapamil has therapeutic potential in improving acute motor function after ICH. Further investigations are needed to confirm whether verapamil treatment could be a promising candidate for clinical trials.

A Systematic Review of Inflammatory Cytokine Changes Following Aneurysmal Subarachnoid Hemorrhage in Animal Models and Humans.

Aneurysmal subarachnoid hemorrhage (aSAH) is a severe form of stroke that occurs following rupture of a cerebral aneurysm. Acute inflammation and secondary delayed inflammatory responses, both largely controlled by cytokines, work together to create high mortality and morbidity for this group. The trajectory and time course of cytokine change must be better understood in order to effectively manage unregulated inflammation and improve patient outcomes following aSAH. A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Three different search phrases ("cytokines and subarachnoid hemorrhage," "cytokine levels and subarachnoid hemorrhage," and "cytokine measurement and subarachnoid hemorrhage") were applied across three databases (PubMed, SCOPUS, and the Cochrane Library). Our procedures returned 856 papers. After application of inclusion/exclusion criteria, 95 preclinical animal studies and 41 clinical studies remained. Across studies, 22 different cytokines had been investigated, 5 different tissue types were analyzed, and 3 animal models were utilized. Three main pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) demonstrated reliable increases following aSAH across the included studies. While this is a promising area of research for potential therapeutics, there are gaps in the knowledge base that bar progress for clinical translation of this information. In particular, there is a need for investigations that explore the systemic inflammatory response following injury in a more diverse number of cytokines, the balance of specific pro-/anti- inflammatory cytokines, and how these biomarkers relate to patient outcomes and recovery over time.

The pancreatic cancer immune tumor microenvironment is negatively remodeled by gemcitabine while TGF-ß receptor plus dual checkpoint inhibition maintains antitumor immune cells.

Pancreatic ductal adenocarcinoma (PDA) tumors have a highly immunosuppressive desmoplastic tumor microenvironment (TME) where immune checkpoint inhibition (ICI) therapy has been exceptionally ineffective. Transforming growth factor-ß (TGF-ß) receptor activation leads to cancer and immune cell proliferation and phenotype, and cytokine production leading to tumor progression and worse overall survival in PDA patients. We hypothesized that TGF-ß receptor inhibition may alter PDA progression and antitumor immunity in the TME. Here, we used a syngeneic preclinical murine model of PDA to explore the impact of TGF-ß pathway inhibitor galunisertib (GAL), dual checkpoint immunotherapy (anti-PD-L1 and CTLA-4), the chemotherapy gemcitabine (GEM), and their combinations on antitumor immune responses. Blockade of TGF-ß and ICI in immune-competent mice bearing orthotopically injected murine PDA cells significantly inhibited tumor growth and was accompanied by antitumor M1 macrophage infiltration. In contrast, GEM treatment resulted in increased PDA tumor growth, decreased antitumor M1 macrophages, and decreased cytotoxic CD8+ T cell subpopulation compared to control mice. Together, these findings demonstrate the ability of TGF-ß inhibition with GAL to prime antitumor immunity in the TME and the curative potential of combining GAL with dual ICI. These preclinical results indicate that targeted inhibition of TGF-ß may enhance the efficacy of dual immunotherapy in PDA. Optimal manipulation of the immune TME with non-ICI therapy may enhance therapeutic efficacy.

A Conceptual Model of the Influence of Mindfulness-Based Interventions on Stress and Quality of Life in Patients With Chronic Conditions.

Individuals with chronic conditions are susceptible to stress-related health complications. Left unattended, chronic stress exacerbates inflammation, diminishes quality of life (QOL), and increases all-cause mortality. Here, we suggest a theoretical framework promoting the use of mindfulness-based interventions (MBIs) in patients with chronic conditions and a conceptual model of how MBIs may influence stress and QOL.

Strategies to enhance the success of mid-career nurse scientists.

BACKGROUND: The mid-career nurse scientist, defined as an associate professor with/without tenure, is often faced with a multitude of challenges and opportunities PURPOSE: This paper shares strategies to assist mid-career scientists as they juggle required career demands and navigate the mid-career phase in pursuit of the rank of full professor. METHOD: A review of the literature was performed on mid-career nurse scientists. DISCUSSION: A combination of increased research responsibilities, increased institutional teaching and service demands, and dwindling support can result in a sense of overwhelm and burnout. The mid-career nurse scientist must balance several balls in the air at one time to remain successful. CONCLUSION: Strategies aligned with the Ecological Framework, focus on intrapersonal, interpersonal, institutional, organizational, and public policy domains to provide a wide scope of strategies that target the mid-career scientist and engage the larger nursing community.

Lessons Learned From Pairing Education-Intensive and Research-Intensive Faculty to Increase Scholarship in Nursing.

ABSTRACT: Many nurse faculty find scholarship goals difficult to achieve while also maintaining education, practice, and service duties. This article describes a partnership between education-intensive and research-intensive faculty members that increased scholarly output. Challenges included conflicting schedules and responsibilities and an increasing desire to accomplish more than was possible in the allotted time. Differences in educational preparation and experiences were found to be a facilitator that enabled the team to be more productive. An equally felt commitment to the process and dedicated meetings also helped this team to be successful.

Genotype-expression interactions for BDNF across human brain regions.

BACKGROUND: Genetic variations in brain-derived neurotrophic factor (BDNF) are associated with various psychiatric disorders including depression, obsessive-compulsive disorder, substance use disorders, and schizophrenia; altered gene expression triggered by these genetic variants may serve to create these phenotypes. But genotype-expression interactions for this gene have not been well-studied across brain regions relevant for psychiatric disorders. RESULTS: At false discovery rate (FDR) of 10% (q < 0.1), a total of 61 SNPs were associated with BDNF expression in cerebellum (n = 209), 55 SNPs in cortex (n = 205), 48 SNPs in nucleus accumbens (n = 202), 47 SNPs in caudate (n = 194), and 58 SNPs in cerebellar hemisphere (n = 175). We identified a set of 30 SNPs in 2 haplotype blocks that were associated with alterations in expression for each of these 5 regions. The first haplotype block included variants associated in the literature with panic disorders (rs16917204), addiction (rs11030104), bipolar disorder (rs16917237/rs2049045), and obsessive-compulsive disorder (rs6265). Likewise, variants in the second haplotype block have been previously associated with disorders such as nicotine addiction, major depressive disorder (rs988748), and epilepsy (rs6484320/rs7103411). CONCLUSIONS: This work supports the association of variants within BDNF for expression changes in these key brain regions that may contribute to common behavioral phenotypes for disorders of compulsion, impulsivity, and addiction. These SNPs should be further investigated as possible therapeutic and diagnostic targets to aid in management of these and other psychiatric disorders.

Enhancing Research Through the Use of the Genotype-Tissue Expression (GTEx) Database.

Despite a growing interest in multi-omic research, individual investigators may struggle to collect large-scale omic data, particularly from human subjects. Publicly available datasets can help to address this problem, including those sponsored by the NIH Common Fund, such as the Genotype-Tissue Expression (GTEx) database. This database contains genotype and expression data obtained from 54 non-diseased tissues in human subjects. But these data are often underutilized, because users may find the browsing tools to be counterintuitive or have difficulty navigating the procedures to request controlled data access. Furthermore, there is limited knowledge of these resources among nurse scientists interested in incorporating such information into their programs of research. This article outlines the procedures for using the GTEx database. Next, we provide one exemplar of using this resource to enhance existing research by investigating expression of dopamine receptor type 2 (DRD2) across brain tissues in human subjects.

Elevated liver function tests in COVID-19: Causes, clinical evidence, and potential treatments.

COVID-19 causes severe respiratory and multiorgan failure, including liver damage and elevated transaminase levels. This article addresses the potential causes of liver function abnormalities in patients diagnosed with COVID-19 and management approaches for NPs focusing on preventing and alleviating liver injury.

Expression of Dopamine-Related Genes in Four Human Brain Regions.

A better understanding of dopaminergic gene expression will inform future treatment options for many different neurologic and psychiatric conditions. Here, we utilized the National Institutes of Health's Genotype-Tissue Expression project (GTEx) dataset to investigate genotype by expression associations in seven dopamine pathway genes (ANKK1, DBH, DRD1, DRD2, DRD3, DRD5, and SLC6A3) in and across four human brain tissues (prefrontal cortex, nucleus accumbens, substantia nigra, and hippocampus). We found that age alters expression of DRD1 in the nucleus accumbens and prefrontal cortex, DRD3 in the nucleus accumbens, and DRD5 in the hippocampus and prefrontal cortex. Sex was associated with expression of DRD5 in substantia nigra and hippocampus, and SLC6A3 in substantia nigra. We found that three linkage disequilibrium blocks of SNPs, all located in DRD2, were associated with alterations in expression across all four tissues. These demographic characteristic associations and these variants should be further investigated for use in screening, diagnosis, and future treatment of neurological and psychiatric conditions.

Applying Social Determinants of Health to Nursing Education Using a Concept-Based Approach.

BACKGROUND: The assessment of a patient's social determinants of health (SDOH) may uncover potentially modifiable factors that each contribute to or detract from the health and wellness of individuals, families, and groups. A concept-based curriculum may offer advantages for introducing SDOH assessment to nursing students. METHOD: The concept of SDOH was threaded throughout a baccalaureate concept-based curriculum using innovative and team-based learning strategies. RESULTS: A concept-based curriculum provides an effective platform for introducing SDOH topics in nursing education, but many of the learning activities also could be incorporated into traditional curricula. CONCLUSION: Nursing education should incorporate teaching about SDOH to prepare students for high-quality nursing practice and better patient advocacy. Assessment of SDOH also allows treatment plans to be tailored to the needs of that patient or population, which in turn may improve health outcomes. [J Nurs Educ. 2020;59(5):293-296.].

Gene co-expression networks are associated with obesity-related traits in kidney transplant recipients.

BACKGROUND: Obesity is common among kidney transplant recipients; However biological mediators of obesity are not well understood in this population. Because subcutaneous adipose tissue can be easily obtained during kidney transplant surgery, it provides a unique avenue for studying the mechanisms of obesity for this group. Although differential gene expression patterns were previously profiled for kidney transplant patients, gene co-expression patterns can shed light on gene modules not yet explored on the coordinative behaviors of gene transcription in biological and disease processes from a systems perspective. METHODS: In this study, we collected 29 demographic and clinical variables and matching microarray expression data for 26 kidney transplant patients. We conducted Weighted Gene Correlation Network Analysis (WGCNA) for 5758 genes with the highest average expression levels and related gene co-expression to clinical traits. RESULTS: A total of 35 co-expression modules were detected, two of which showed associations with obesity-related traits, mainly at baseline. Gene Ontology (GO) enrichment was found for these two clinical trait-associated modules. One module consisting of 129 genes was enriched for a variety of processes, including cellular homeostasis and immune responses. The other module consisting of 36 genes was enriched for tissue development processes. CONCLUSIONS: Our study generated gene co-expression modules associated with obesity-related traits in kidney transplant patients and provided new insights regarding the cellular biological processes underlying obesity in this population.