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Urine Proteomic Signatures of Kidney Function Decline after Hospitalization
No full textBACKGROUND: Urine proteomics may provide mechanistic insights on why patients experience a higher risk of kidney function decline after hospitalization. METHDOS: In 174 patients with and without acute kidney injury (AKI) from the Assessment, Serial Evaluation, and Subsequent Sequelae in AKI (ASSESS-AKI) cohort, we used Olink to profile 2783 urine proteins collected at 3 months post-hospitalization and determined their association with estimated glomerular filtration rate (eGFR) decline during median [IQR] of 5.1[4.0-6.0] years follow-up. In four independent cohorts including the Kidney Precision Medicine Project (KPMP), we determined if proteins were differentially expressed with AKI. We used weighted correlation network analysis to determine proteins\u27 cellular enrichment in the kidney transcriptome (single-cell and spatial transcriptomics) in patients with AKI receiving research kidney biopsy. RESULTS: We identified 387 and 10 proteins associated with faster and slower eGFR decline, respectively, most of which were differentially expressed in patients at the time of AKI. Among these proteins, 283 (71%) were expressed by kidney cells in participants with AKI from KPMP. The expression formed 3 clusters enriched in the proximal tubule, degenerative tubule and myeloid cells, and stromal cells, and correlated with histopathological features of AKI, such as tubular injury, interstitial inflammation, and fibrosis, respectively. CONCLUSION: Urinary proteins reflecting degenerative tubular injury, inflammation, and fibrosis are associated with eGFR decline in recently hospitalized patients. FUNDING: The Kidney Precision Medicine Project (KPMP) is supported by the National Institute of Diabetes and Digestive Kidney Diseases (NIDDK) through the following grantsU01DK133081, U01DK133091, U01DK133092, U01DK133093, U01DK133095, U01DK133097, U01DK114866, U01DK114908, U01DK133090, U01DK133113, U01DK133766, U01DK133768, U01DK114907, U01DK114920, U01DK114923, U01DK114933, U24DK114886, UH3DK114926, UH3DK114861, UH3DK114915, and UH3DK114937 We gratefully acknowledge the essential contributions of our patient participants and support of the American public though their tax dollars. SM is supported by NIDDK Grant K23DK128358
Climate change and the global food chain: a catalyst for emerging infectious diseases?
No full textBACKGROUND: Climate change is disrupting the global food chain, affecting food production, delivery and safety. Extreme weather events disrupt the quality of food and water, while rising temperatures accelerate the spread of microbes. Habitat destruction also forces wildlife in close proximity to people, increasing the risk of zoonotic diseases. Threatening global health seriously, these disturbances also increase the probability of infectious and food-borne diseases. METHOD: A narrative review of literature data from WHO publications, Google Scholar and PubMed. The review examines the impacts of climate change on agriculture, food supply systems, and the associated transmission of infectious disease - specifically zoonotic and food-borne diseases. RESULTS: As temperatures increase, the germs multiply easily - and the risk of E. coli and Salmonella goes up. Waterborne diseases such as Norovirus and Hepatitis A are more likely to spread in typified extreme weather conditions such as floods. Ecosystem changes push humans and animals into a closer relationship that can lead to zoonotic spillovers, such as the Nipah virus and COVID-19. The growth of animal production and international trade exacerbates antimicrobial resistance (AMR) issues, imposing challenges to disease control. CONCLUSION: Climate change is a critical public health emergency with risks of zoonotic and food-borne illnesses alarmingly on the rise. This is an important step toward a One Health approach, which also addresses the integration of human, animal, and environmental health, as well as strengthens food safety regulations and enhances disease surveillance. It needs immediate international cooperation to construct a robust and sustainable food system that reduces health hazards. CLINICAL TRIAL NUMBER: Not applicable
Intranasal administration of KCNN2 blocking peptide improves deficits in cognitive flexibility in mouse model of Fetal Alcohol Spectrum Disorders
No full textBACKGROUND: Fetal Alcohol Spectrum Disorders (FASD) show a myriad of cognitive and neurological deficits, with the prevalence estimated to be 1-5 % in children. To date, there are no effective treatments for these deficits in FASD. In a mouse model of FASD, daily intraperitoneal administration of a KCNN2 blocking peptide has been shown to improve motor learning deficits due to upregulation of KCNN2 channels. This study investigates whether intranasal administration of a KCNN2 blocking peptide, Lei-Dab7, can improve cognitive flexibility, specifically reversal learning deficits, in these mice. METHODS: We utilized a mouse model of prenatal alcohol exposure. Cognitive flexibility was assessed using the water T-maze test at postnatal day 40 (P40). Lei-Dab7\u27s specificity and cytotoxicity were evaluated in vitro, and intranasal delivery efficiency was confirmed through immunohistochemistry, quantifying its distribution and binding to neurons with elevated KCNN2 expression in the prefrontal cortex (PFC). RESULTS: Lei-Dab7 showed high specificity and negligible cytotoxicity in vitro. Intranasal administration efficiently delivered Lei-Dab7 to the PFC, where it specifically bound to neurons expressing increased KCNN2 channels. Behavioral tests demonstrated that Lei-Dab7 significantly improved cognitive flexibility, reversing the deficits in the water T-maze test seen in ethanol-exposed mice, without apparent acute physiological adverse effects. CONCLUSIONS: Intranasal administration of KCNN2 blockers, such as Lei-Dab7, represents a promising, non-invasive therapeutic approach for treating cognitive inflexibility and possibly other cognitive dysfunctions associated with FASD
Longitudinal associations and interactions of heat and metal(loid) exposure with kidney outcomes in Mexican agricultural workers
No full textBACKGROUND: Agricultural workers perform physically demanding labor in extreme heat, increasing their risk for kidney injury. Agricultural workers are also exposed to nephrotoxic metal(loid)s, yet little research examines the combined effects of heat and metal(loid) exposure on kidney health. OBJECTIVE: This study assessed how simultaneous exposure to metal(loid)s and heat impacts acute kidney injury (AKI) and kidney function over time. METHODS: As part of a longitudinal study, we followed a cohort of male grape farmworkers near the Arizona-Sonora border (n = 77), collecting biological samples and questionnaires at two timepoints: at the beginning (i.e., baseline) and again at the end of the work season (i.e., follow-up). Physiological strain index (PSI) was estimated using inner ear temperature and heart rate. Urine samples were analyzed for metal(loid)s, specific gravity, and neutrophil gelatinase-associated lipocalin (uNGAL), while blood serum was used to calculate estimated glomerular filtration rate (eGFR). Linear mixed effect and linear regression models evaluated the impact of metal(loid)s and PSI on kidney health, incorporating interaction terms for chronic (seasonal) and acute (PSI) heat exposure. RESULTS: Participants averaged 29 years old, with 35 % primarily speaking an Indigenous language. Urinary arsenic (β = 0.35, 95 %CI: 0.15, 0.55), cadmium (β = 0.27, 95 %CI: 0.14, 0.40), and chromium (β = 0.54, 95 %CI: 0.20, 0.88) were associated with increased uNGAL, while increased uranium was associated with reduced eGFR (β = -2.45, 95 %CI: 4.81, -0.08). Effects were attenuated in stratified models. Interactions showed chronic heat exposure exacerbated arsenic and cadmium\u27s effects (arsenic-uNGAL, p \u3c 0.01; cadmium-uNGAL, p = 0.02). No significant interactions were observed for acute heat stress. DISCUSSION: Heat may modify the impact of toxic metal(loid)s on kidney health, emphasizing the need for workplace policies that mitigate heat stress among agricultural workers
Cannabis Use Among Adolescents and Young Adults with Cancer: A Scoping Review
No full textThere have been recent increases in cannabis use for medical and non-medical (i.e., recreational ) purposes. One prominent medical use is for cancer-related symptoms. Young adults with a cancer history may have unique cannabis use characteristics, yet little research has examined this topic. This scoping review assessed the literature on cannabis use among young adults with a history of cancer. In October 2024, we conducted a MEDLINE/PubMed search for empirical, peer-reviewed articles written in English. Inclusion criteria were (1) primary research, (2) included participants ages 18-39 previously diagnosed with cancer, (3) included data on cannabis use, and (4) written in English. This review included 15 articles, which varied in timing of cancer diagnosis (e.g., childhood, adolescence, young adulthood) and age at data collection (e.g., 15-25, 18-39). Most (n = 11) were cross-sectional survey studies; others were longitudinal (n = 2), observational (n = 1), or chart reviews (n = 1). Results varied regarding cannabis use prevalence among cancer survivors compared to peers without a cancer diagnosis, as well as whether certain treatment-related factors were associated with use. Several studies documented medical use motives (e.g., nausea, pain, insomnia, mood), with some indication of effectiveness. Existing research has largely focused on medical use and use during treatment; less research has assessed use outside of cancer treatment or for non-medical reasons among individuals with a cancer diagnosis. Young adults with a cancer history may have unique cannabis use characteristics given their likely use for both medical and non-medical purposes
Testing the reliability and validity of the nurse practitioner student competency assessment
No full textBACKGROUND: The American Association of Colleges of Nursing (AACN) Essentials (2021) and the National Organization of Nurse Practitioner Faculties (NONPF) Role Competencies (2022) outline professional nursing competencies, resulting in a shift toward Nurse Practitioner (NP) competency-based education. PURPOSE: To evaluate the reliability and validity of the Nurse Practitioner Student Competency Assessment (NPSCA), a revised instrument measuring person-centered competencies established by AACN and NONPF. METHODOLOGY: Fifty-three students from four NP programs in their first clinical experience participated in the study. Each student performed one simulation, which was video-recorded. Two faculty members reviewed and scored each student\u27s video recording using the NPSCA and the Virginia Commonwealth University (VCU) Scale, an instrument similar to those used by NP programs. The faculty ratings were collected using an online survey program. RESULTS: The final version of the NPSCA has 17 items. Eight faculty members rated the items on a scale from 1 (not very relevant) to 4 (very relevant), with 100% agreement that the items were relevant or very relevant, indicating sufficient content validity. Internal consistency: α = 0.884-0.895. Correlations between the NPSCA and the VCU scale were r = 0.288, p = .036 and r = 0.589, p \u3c .001, respectively. CONCLUSIONS: The evidence supports the reliability and validity of the NPSCA. Its internal consistency is excellent, and the content validity and criterion-related validity were sufficiently supported. IMPLICATIONS: With a shortage of reliable and valid tools to assess NP graduates, the NPSCA may play a role in evaluating and ensuring the readiness of NP graduates for practice
How Does Part-Time Work Affect Chinese Undergraduate Students\u27 Mental Health and Academic Performance?
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