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《Genetics in medicine》2023,25(3):100351
PurposeNephrolithiasis (NL) affects 1 in 11 individuals worldwide, leading to significant patient morbidity. NL is associated with nephrocalcinosis (NC), a risk factor for chronic kidney disease. Causative genetic variants are detected in 11% to 28% of NL and/or NC, suggesting that additional NL/NC-associated genetic loci await discovery. Therefore, we employed genomic approaches to discover novel genetic forms of NL/NC.MethodsExome sequencing and directed sequencing of the OXGR1 locus were performed in a worldwide NL/NC cohort. Putatively deleterious, rare OXGR1 variants were functionally characterized.ResultsExome sequencing revealed a heterozygous OXGR1 missense variant (c.371T>G, p.L124R) cosegregating with calcium oxalate NL and/or NC disease in an autosomal dominant inheritance pattern within a multigenerational family with 5 affected individuals. OXGR1 encodes 2-oxoglutarate (α-ketoglutarate [AKG]) receptor 1 in the distal nephron. In response to its ligand AKG, OXGR1 stimulates the chloride-bicarbonate exchanger, pendrin, which also regulates transepithelial calcium transport in cortical connecting tubules. Strong amino acid conservation in orthologs and paralogs, severe in silico prediction scores, and extreme rarity in exome population databases suggested that the variant was deleterious. Interrogation of the OXGR1 locus in 1107 additional NL/NC families identified 5 additional deleterious dominant variants in 5 families with calcium oxalate NL/NC. Rare, potentially deleterious OXGR1 variants were enriched in patients with NL/NC compared with Exome Aggregation Consortium controls (χ2 = 7.117, P = .0076). Wild-type OXGR1-expressing Xenopus oocytes exhibited AKG-responsive Ca2+ uptake. Of 5 NL/NC-associated missense variants, 5 revealed impaired AKG-dependent Ca2+ uptake, demonstrating loss of function.ConclusionRare, dominant loss-of-function OXGR1 variants are associated with recurrent calcium oxalate NL/NC disease. 相似文献
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BackgroundPatterns of alcohol use change from adolescence to adulthood and may differ based on race/ethnicity, sexual identity, and education. If alcohol use measures do not operate consistently across groups and developmental periods, parameter estimates and conclusions may be biased.ObjectivesTo test the measurement invariance of a multi-item alcohol use measure across groups defined by race/ethnicity, sexual identity, and college education during the transition to adulthood.MethodsUsing three waves from the National Longitudinal Study of Adolescent to Adult Health, we tested configural, metric, and scalar invariance of a 3-item alcohol use measure for groups defined by race/ethnicity, sexual identity, and college education at three points during the transition to adulthood. We then assessed longitudinal measurement invariance to test the feasibility of modeling developmental changes in alcohol use within groups defined by these characteristics.ResultsOverall, findings confirm notable variability in the construct reliability of a multi-item alcohol use measure during the transition to adulthood. The alcohol use measure failed tests of metric and scalar invariance, increasingly across ages, both between- and within-groups defined by race/ethnicity, sexual identity, and college education, particularly among females.ConclusionsMeasurement testing is a critical step when utilizing multi-item measures of alcohol use. Studies that do not account for the effects of group or longitudinal measurement non-invariance may be statistically biased, such that recommendations for risk and prevention efforts could be misguided. 相似文献
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Because nursing is a high risk profession in terms of occupational health and safety (OHS), the topic of OHS is an important component of student nurse education and practice. Seeking ways to enhance curricular content and foster student health, safety and wellbeing is an ongoing pursuit. This pilot study explored nursing student perspectives about OHS in the clinical setting to develop an understanding of student views that could enlighten teaching about this topic within the undergraduate nursing course. Focus groups were held with pre-registration student nurses in two discrete cohort levels (first and third year). Themes were identified from the focus group discussion about trust, knowledge and responsibility. The students demonstrated a sound grasp of clinical hazards and associated administrative controls. Strengthening student awareness of higher order controls and their evaluation would augment their knowledge of legislative requirements. Students may benefit from learning about a risk management approach to OHS which would provide them with a structured basis for problem solving. This may assist them with clinical reasoning about health and safety issues and empower them in aspects of self-care. 相似文献
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《Health policy (Amsterdam, Netherlands)》2018,122(11):1249-1254
ObjectiveThe German Patients' Rights Act (PRA), promulgated on February 25, 2013, was created to enhance transparency of patients' rights. This prospective study aimed to objectively measure physicians' comprehension of the PRA.MethodsWe generated a controlled study design, developing a questionnaire consisting of six case scenarios with 4–7 dichotomous items each. The survey concluded with seven 5-point-Likert scale questions, dealing with the PRA’s effects. Physicians teaching at the Westfälische Wilhelms-Universität (WWU) Münster served as the intervention group, and medical students from WWU Münster at the beginning of their clinical education formed the control group. Physicians were surveyed in November 2015; students were surveyed in February 2016.ResultsA total 56 completed surveys of physicians and 134 of students were analyzed. Of a total 33 points, on average physicians answered 21.04 (95% confidence interval (CI) 20.43–21.64) items correctly, a significantly higher result than students' 19.74 (95% CI 19.31–20.17) points (p < 0.001; Hedges' g = 0.53). Estimations of the PRA’s effects were ambiguous. Students agreed with the PRA’s supporting effect more often than physicians (p < 0.001) whereas physicians felt increased uncertainty arising from the PRA.ConclusionComprehension of the PRA increases significantly over the course of medical work experience; however, this comprehension is limited among medical experts. The PRA leads to ambiguity and uncertainty in the medical decision-making process. 相似文献
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BackgroundTo describe the study methods, baseline characteristics and burden of study procedures of an intervention designed to reduce family stress symptoms through early support from the palliative care team. Length of stay of ≥ 8 days was the trigger for early palliative care involvement.MethodsCluster-randomized trial with children as the unit of randomization. Up to 3 family members per child were recruited. Family stress symptoms were recorded at baseline, discharge from the ICU, and 3 months post-enrollment. Questionnaire burden was assessed on a 1–10 point scale at each time point and open-ended comments were analyzed to describe the participants' experience in the study.Results380 family members of 220 children (control = 115 children and 204 family members; intervention = 105 children and 176 family members) were recruited, which represented 50% of all eligible families. Most family participants were parents (86% control; 92% intervention) and female (66% both groups). Retention rates were high through the 3-month follow-up: 93% and 90% for the control and intervention groups respectively. Questionnaire burden was very low: mean (sd) scores were 1.1 (1.6), 0.7 (1.5), and 0.9 (1.6) for the baseline, discharge and follow-up questionnaires, respectively. Comments suggest that participation was beneficial by promoting reflection and self-awareness about stress, coping and resilience, and feeling cared for because the intervention and questionnaires focused on their own well-being.ConclusionsThe participants' comments regarding the focus on them as the point of intervention reflects the value of conducting research with family members of seriously ill children during ICU stays. 相似文献
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