Background/Aims: Klotho is a multifunctional protein expressed predominantly in kidney tubular epithelium. Here, we investigated the protective effects of Klotho on necroptosis in renal ischemic-reperfusion injury (IRI) and the role of oxidative stress in this process. Methods: Mice were subjected to bilateral renal pedicle clamping. Mouse renal tubular epithelial (TCMK-1) cells were exposed to hypoxia/reoxygenation (H/R) or H2O2. Kidney samples from acute kidney injury (AKI) patients and controls were examined by immunofluorescence. Klotho protein and N-acetyl-L-cysteine (NAC) were used to define their roles in mediating necroptosis. Necroptosis was assessed by TUNEL staining, immunoblotting, and real-time PCR. Oxidative stress was studied via ELISA, immunoblotting, colorimetric, and thiobarbituric acid reactive substances assays. Results: Renal IRI induced Klotho deficiency in the serum and kidney, but an increase in the urine. The levels of the necroptotic markers receptor-interacting protein kinase (RIP) 1, RIP3, IL-1β, and TUNEL-positive cells increased after IRI; all increases were ameliorated by Klotho. In TCMK-1 cells, Klotho and NAC attenuated the elevation in RIP1, RIP3, and LDH release induced by H/R or H2O2. Moreover, Klotho decreased the levels of oxidative stress biomarkers and elevated superoxide dismutase 2 expression in both in vivo and in vitro experiments. Studies in human samples further confirmed the Klotho deficiency and increased formation of RIP3 puncta in AKI kidneys. Conclusion: Klotho protects tubular epithelial cells from IRI and its anti-necroptotic role may be associated with oxidative stress inhibition.
Background and Objectives Many investigators of Alzheimer’s disease and related dementias (AD/ADRD) are unfamiliar with the embedded pragmatic clinical trials (ePCTs) and the indispensable pilot phase preceding ePCTs. This paper provides a much-needed example for such a pilot phase and discusses implementation barriers and additional infrastructure and implementation strategies developed in preparation for a nationwide AD/ADRD ePCT. Research Design and Methods Two pilot trials were conducted in two hospices sequentially to refine and test Aliviado Dementia Care-Hospice Edition, a complex quality improvement intervention for advanced dementia symptom management. Readiness for the subsequent full-scale ePCT was assessed by three milestones: ≥80% training completion rate (“feasibility”), ≥80% post-training survey respondents indicating intention for practice changes (“applicability”), and at least one Aliviado care plan/assessment instrument administered in ≥75% of dementia patients admitted to home hospice within one-month post training (“fidelity”). Results Participants included 72 interdisciplinary team (IDT) members and 11 patients with AD/ADRD across the pilots. Feasibility, applicability, and fidelity outcomes (92%, 93%, and 100%, respectively) all surpassed the pre-established milestones (80%, 80%, and 75%). Main implementation challenges were related to hospice staff turnover, integration of the Aliviado toolbox materials within the electronic health records, and hospices’ limited research experience and infrastructure. Discussion and Implications This pilot phase demonstrated feasibility, applicability, and fidelity required to proceed to the full-scale ePCT. Our study findings and discussions of additional infrastructure and implementation strategies developed following the pilot phase can inform researchers and clinicians interested in conducting AD/ADRD-related pilot studies for ePTCs or quality improvement initiatives. Clinical Trial Number NCT03681119.
Objective COVID-19 has disproportionately impacted nursing homes (NHs) with large shares of Black residents. We examined the associations between the proportion of Black residents in NHs and COVID-19 infections and deaths, accounting for structural bias (operationalized as county-level factors) and stratifying by urbanicity/rurality. Design This was a cross-sectional observational cohort study using publicly available data from the LTCfocus, Centers for Disease Control and Prevention (CDC) Long-Term Care Facility COVID-19 Module, and the NYTimes county-level COVID-19 database. Four multivariable linear regression models omitting and including facility characteristics, COVID-19 burden, and county-level fixed effects were estimated. Setting and Participants: 11,587 US NHs that reported data on COVID-19 to the CDC and had data in LTCfocus and NYTimes from January 20 th , 2020 through July 19 th , 2020. Measures Proportion of Black residents in NHs (exposure); COVID-19 infections and deaths (main outcomes). Results The proportion of Black residents in NHs were as follows: none= 3,639 (31.4%), <20%= 1,020 (8.8%), 20-49.9%= 1,586 (13.7%), ≥50= 681 (5.9%), not reported= 4,661 (40.2%). NHs with any Black residents showed significantly more COVID-19 infections and deaths than NHs with no Black residents. There were 13.6 percentage points more infections and 3.5 percentage points more deaths in NHs with ≥50% Black residents than in NHs with no Black residents (p<.001). While facility characteristics explained some of the differences found in multivariable analyses, county-level factors and rurality explained more of the differences. Conclusions and Implications It is likely that attributes of place, such as resources, services, and providers, important to equitable care and health outcomes are not readily available to counties where NHs have greater proportions of Black residents. Structural bias may underlie these inequities. It is imperative that support be provided to NHs that serve greater proportions of Black residents while considering the rurality of the NH setting.
Background: Quality of life (QoL) is an important component of individuals’ general well-being, particularly in older adults. However, factors influencing QoL among older adults in low- and middle-income countries (LMICs) have not been fully examined. Furthermore, the role of gender differences in relation to QoL in multiple LMICs has also not been examined in detail. Methods: This study used data from the World Health Organization’s Study on Global AGEing and adult health (SAGE), Wave-1. Based on a literature review of existing works, a set of variables—an independent variable and covariates—were selected. The study sample consisted of 33,019 participants aged 50 years and above from China, Ghana, India, Russia, and South Africa. Multivariate linear regression models were estimated with the World Health Organization QoL scores as the dependent variable. To preserve the analytical sample size, multiple imputation was used to account for missing data. Results: L The results showed that generally, male older adults reported a better QoL than female older adults across all of the countries. The associations between QoL and sociodemographic factors, health-related factors, and social support factors among older adults differed according to country. Conclusions: This study provides a better understanding of QoL among older adults in LMICs, which can help prepare LMICs to better address the QoL of older adults. The results of this study can be used to develop programs to promote better living standards and services to reduce gender disparities and ultimately, to improve the QoL among older adults in LMICs. Keywords: Quality of life, gender inequality, older adults, low- and middle-income country
The activation of the heart inward rectifier potassium channel (I(K1) ) can reduce the injury of myocardial cells by shortening the action potential duration and reducing intracellular calcium overload. Zacopride is a selective I(K1) agonist and suppresses triggered arrhythmias in rat hearts. This investigation studied the effects of St. Thomas (ST) cardioplegia enriched with Zacopride on the isolated rat heart model. Sprague-Dawley rat hearts were harvested and perfused for 20 minutes with 37°C Krebs-Henseleit (KH) buffer followed by 15 minute perfusion with 4°C calcium-free KH buffer in the Control group (Con, n = 8), ST cardioplegia in the ST group (ST, n = 8) and ST cardioplegia with Zacopride in the STZ group (STZ, n = 8). After 45 minutes of arresting, all hearts were reperfused with 37°C KH buffer for 60 minutes. Hearts in the STZ group arrested faster than the Con and ST groups (9.25 ± 2.38 s vs. 72.25 ± 8.1 s, 12.75 ± 2.87 s). The recovery of the left ventricular developed pressure, ± dP/dtmax, heart rate, and coronary flow in the STZ group is significantly better than the other two groups during reperfusion. Compared with the Con and ST groups, the STZ group showed significant decreases in the maximum carciac troponin I level (P < 0.05) and the infarct size (P < 0.05). The superoxide dismutase level in the STZ group increased during the first 20 minutes of reperfusion (P < 0.05). ST cardioplegia enriched with Zacopride has beneficial effects against ischemia-reperfusion injury in this isolated rat heart model.
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