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Background: 25-hydroxy vitamin D (Vit D)-deficiency is common among patients with chronic kidney disease (CKD) and contributes to cardiovascular disease (CVD). African Americans (AAs) suffer disproportionately from CKD and CVD, and 80% of AAs are Vit D-deficient. The impact of Vit D repletion on cardio-renal biomarkers in AAs is unknown. We examined Vit D repletion on full-length osteopontin (flOPN), c-terminal fibroblast growth factor-23 (FGF-23), and plasminogen activator inhibitor-1 (PAI-1), which are implicated in vascular and kidney pathology. Methods: We performed a randomized, placebo-controlled study of high-risk AAs with Vit D deficiency, treated with 100,000 IU Vit D3 (cholecalciferol; n = 65) or placebo (n = 65) every 4 weeks for 12 weeks. We measured kidney function (CKD-EPI eGFR), protein-to-creatinine ratio, vascular function (pulse wave velocity; PWV), augmentation index, waist circumference, sitting, and 24-h-ambulatory blood pressure (BP), intact parathyroid hormone (iPTH) and serum calcium at baseline and study end, and compared Vit D levels with laboratory variables. We quantified plasma FGF-23, PAI-1, and flOPN by enzyme-linked immunosorbent assay. Multiple regression analyzed the relationship between log flOPN, FGF-23, and PAI-1 with vascular and renal risk factors. Results: Compared to placebo, Vit D3 repletion increased Vit D3 2-fold (p < 0.0001), decreased iPTH by 12% (p < 0.01) and was significantly correlated with PWV (p < 0.009). Log flOPN decreased (p = 0.03), log FGF-23 increased (p = 0.04), but log PAI-1 did not change. Multiple regression indicated association between log flOPN and PWV (p = 0.04) and diastolic BP (p = 0.02), while log FGF-23 was associated with diastolic BP (p = 0.05), and a trend with eGFR (p = 0.06). Conclusion: Vit D3 repletion may reduce flOPN and improve vascular function in high risk AAs with Vit D deficiency.

Along with early-onset cancers, multiple primary cancers (MPCs) are likely resulting from increased genetic susceptibility; however, the associated predisposition genes or prevalence of the pathogenic variants genes in MPC patients are often unknown. We screened 71 patients with MPC of the stomach, colorectal, and endometrium, sequencing 65 cancer predisposition genes. A subset of 19 patients with early-onset MPC of stomach and colorectum were further evaluated for variants in cancer related genes using both normal and tumor whole exome sequencing. Among 71 patients with MPCs, variants classified to be pathogenic were observed in 15 (21.1%) patients and affected Lynch Syndrome (LS) genes: MLH1 (n = 10), MSH6 (n = 2), PMS2 (n = 2), and MSH2 (n = 1). All carriers had tumors with high microsatellite instability and 13 of them (86.7%) were early-onset, consistent with LS. In 19 patients with early-onset MPCs, loss of function (LoF) variants in RECQL5 were more prevalent in non-LS MPC than in matched sporadic cancer patients (OR = 31.6, 2.73-1700.6, p = 0.001). Additionally, there were high-confidence LoF variants at FANCG and CASP8 in two patients accompanied by somatic loss of heterozygosity in tumor, respectively. The results suggest that genetic screening should be considered for synchronous cancers and metachronous MPCs of the LS tumor spectrum, particularly in early-onset. Susceptibility variants in non-LS genes for MPC patients may exist, but evidence for their role is more elusive than for LS patients.

ObjectiveAfrican Americans (AA) suffer disproportionately from diabetic nephropathy (DN). C-reactive protein (CRP) has been associated with prevalent DN, but its association with incident DN in AA is unknown. We examined hs-CRP and incident DN in AA.Research design and methodsWe conducted a longitudinal analysis of data from exams 1, 2, and 3 in 4,043 eligible Jackson Heart Study (JHS) participants. Participants with DN or without hs-CRP at exam 1 were excluded. Incident DN was defined as urinary albumin-to-creatinine ratio (ACR) >30 mg/g or self-reported dialysis/transplantation and type 2 diabetes mellitus (DM) or HbA1c >6.5% by exam 2 or 3 among participants free of DN at exam 1. Kaplan-Meier curves examined DN event-free survival probability by hs-CRP. With Cox proportional hazards regression we estimated hazard ratios (HRs) and 95% CI for DN by hs-CRP tertiles, adjusting for demographics and clinical and laboratory data.ResultsDuring 7.8 years of median follow-up time, participants who developed DN had significantly higher baseline hs-CRP, age, fasting glucose, triglycerides, ACR, systolic blood pressure, waist circumference, and duration of DM (P < 0.05). The overall incident rate of DN was 7.9%. The mean time to incident DN was shorter for participants with hs-CRP in the high tertile (>4.24 mg/L) than in the low tertile (

Chronic kidney disease (CKD) is a major non-communicable disease associated with high rates of premature morbidity and mortality. The prevalence of hypovitaminosis D (deficiency of 25(OH)D or 25D) is greater in racial/ethnic minorities and in patients with CKD than the general population. Low 25D is associated with bone and mineral disorders as well as immune, cardiometabolic and cardiovascular (CV) diseases. Thus, it has been suggested that low 25D contributes to the poor outcomes in patients with CKD. The prevalence of hypovitaminosis D rises progressively with advancing severity of kidney disease with over 30% of patients with CKD stage 3 and 70% patients with CKD stage 5 estimated to have low levels of 25D. This report describes several of the abnormal physiologic and counter-regulatory actions related to low 25D in CKD such as those in oxidative stress and inflammatory systems, and some of the preclinical and clinical evidence, or lack thereof, of normalizing serum 25D levels to improve outcomes in patients with CKD, and especially for the high risk subset of racial/ethnic minorities who suffer from higher rates of advanced CKD and hypovitaminosis D.

Rising health concerns regarding chronic diseases call for exploring natural sources of antioxidants and factors that influence their activity. This study evaluated the diversity of 112 sesame germplasms from Africa and Asia based on ten agronomic traits (seven quantitative and three qualitative), two antioxidant activities (ABTS and DPPH radical scavenging activities), and the content of one metabolite (TPC). TPC, DPPH, and ABTS were in the ranges of 4.98–87.88 µg GAE/mg DE, 3.97–46.23 µg AAE/mg DE, and 3.42–176.01 µg TE/mg DE, respectively. Statistical analyses revealed significant variations in agronomic traits, TPC, and antioxidant activities among the sesame germplasms (p < 0.05). Furthermore, the individual and interaction effects of seed color and the continent of origin on the levels of the quantitative traits, TPC, ABTS, and DPPH were analyzed, and the correlation among the traits was further evaluated. Diversity in TPC, ABTS, and DPPH was significantly associated with seed color and most of the quantitative agronomic traits (p < 0.05) but not with continent of origin. Principal component analysis revealed TPC, ABTS, DPPH, and five quantitative traits as the most discriminant traits. In general, six sesame accessions with high TPC and antioxidant activities (IT194356, IT170094, IT29971, IT185998, IT104246, and IT169623) as well as important agronomic traits were identified and, hence, could be used for developing improved sesame varieties. [ABSTRACT FROM AUTHOR]

Purpose: While the intellectual and scientific rationale for research collaboration has been articulated, a paucity of information is available on a strategic approach to facilitate the collaboration within a research network designed to reduce health disparities. This study aimed to (1) develop a conceptual model to facilitate collaboration among biostatisticians in a research network; (2) describe collaborative engagement performed by the Network's Data Coordinating Center (DCC); and (3) discuss potential challenges and opportunities in engaging the collaboration. Methods: Key components of the strategic approach will be developed through a systematic literature review. The Network's initiatives for the biostatistical collaboration will be described in the areas of infrastructure, expertise and knowledge management and experiential lessons will be discussed. Results: Components of the strategic approach model included three Ps (people, processes and programs) which were integrated into expert management, infrastructure management and knowledge management, respectively. Ongoing initiatives for collaboration with non-DCC biostatisticians included both web-based and face-to-face interaction approaches: Network's biostatistical capacities and needs assessment, webinar statistical seminars, mobile statistical workshop and clinics, adjunct appointment program, one-on-one consulting, and on-site workshop. The outreach program, as a face-to-face interaction approach, especially resulted in a useful tool for expertise management and needs assessment as well as knowledge exchange. Conclusions: Although fostering a partnered research culture, sustaining senior management commitment and ongoing monitoring are a challenge for this collaborative engagement, the proposed strategies centrally performed by the DCC may be useful in accelerating the pace and enhancing the quality of the scientific outcomes within a multidisciplinary clinical and translational research network.

Cardiovascular Disease (CVD) and related disorders remain a leading cause of health disparities and premature death for African Americans. Hypovitaminosis D is disproportionately prevalent in African Americans and has been linked to CVD and CVD risk factors including hypertension, diabetes and obesity. Thus, hypovitaminosis D may represent a common pathway influencing CV risk factors in a select subgroup of persons. The purpose of this paper is to report the study design of a prospective eight week prospective double-blind randomized, placebo-controlled trial (n = 330 allocated 2:1 to intervention vs. control) to assess the effect of placebo vs. high-dose oral cholecalciferol (100,000 IU vitamin D3 at baseline and week 2) on 6-week change of select biologic cardiometabolic risk factors (including parathyroid hormone to assess biologic activity, pro-inflammatory/pro-thrombotic/fibrotic markers, insulin sensitivity and vitamin D metabolites) and their relationship to vitamin D administration and modification by vitamin D receptor polymorphisms in overweight, hypertensive African Americans with hypovitaminosis D. Findings from this trial will present insights into potential causal links between vitamin D repletion and mechanistic pathways of CV disease, including established and novel genomic markers.

Purpose: The purpose of this study was to investigate the impact of ethical nursing competence and positive nursing organizational culture on person-centered care among intensive care unit (ICU) nurses. Methods: A cross-sectional research design was adopted for this study. The participants were 156 ICU nurses working at three hospitals in Seoul City and Gyeonggi-do. The data were collected from September 8 to September 30, 2023. The questionnaire consisted of tools for general characteristics, person-centered care, ethical nursing competence, and positive nursing organizational culture. Results: Participants had a mean age of 28.90±5.38 years, and the mean score for person-centered care was 3.65±0.46. Person-centered care was influenced by ethical nursing competence (β=.60, p<.001) and positive nursing organizational culture (β=.21, p=.004). The explanatory power was 32.4% (F=13.36, p<.001, Adj. R2 =.324). Conclusion: Based on the findings of this study, to improve the performance of person-centered nursing by ICU nurses, it is necessary to provide ongoing, systematic education focusing on ethical nursing. This educational initiative should be designed to address the specific ethical challenges encountered in ICU settings. In addition, strengthening managers' active leadership and promoting a positive nursing organizational culture can be expected to improve person-centered nursing performance. [ABSTRACT FROM AUTHOR]

This study examines the dark side of ESG, which has emerged as a new paradigm in that the concept is broad and must respond to stakeholder pressure. This study aims to conceptualize Environmental, Social, and Governance (ESG) stress, or the stress experienced by employees due to ESG, and empirically analyze its impact on mental health. We also examined the moderating effects of job crafting and relationship conflict using the job demand-resource model. Based on a survey of 228 ESG managers with at least five years of work experience, the results of the regression analysis are as follows. First, ESG stress (ESG complexity and ESG uncertainty) was found to cause depression, a negative mental health outcome. Second, job creation was found to moderate depression caused by ESG stress (ESG complexity and ESG uncertainty). Third, relationship conflict was found to reinforce depression caused by ESG stress (ESG complexity and ESG uncertainty). This study is significant because it identifies the relationship between ESG stress and mental health, as ESG has become a requirement for corporate sustainability. Additionally, this study is expected to extend ESG research by examining the moderating effects of job crafting and relationship con-flict from the JD-R on ESG stress and mental health. [ABSTRACT FROM AUTHOR]