23 research outputs found

    Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

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    Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

    Organizational changes in diabetic foot care practices for patients at low and moderate risk after implementing a comprehensive foot care program in Alberta, Canada

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    Abstract Background Neuropathy and vasculopathy can lead to costly and debilitating complications in people with diabetes. The purpose of this study was to evaluate, at an organizational level, uptake of practices included in a diabetic foot care clinical pathway and associated resources. This research focused on patients at low and moderate risk in Alberta, Canada between 2014 to 2019. Methods Serial surveys (2014, 2019) of practices related to screening and care of the feet of people with diabetes. Surveys were administered using a combination of targeted and snowball sampling in order to assess the impact of the clinical pathway first implemented in 2015. The pathway focused on screening, assessment and referral of patients from primary care. High-risk foot teams (HRFT) were established at six sites to provide increased access to specialty care. Comparative statistics were performed to assess differences in footcare practices between 2014 and 2019 using two-tailed Fisher’s exact test or Chi-square test. Results Respondents (n = 104, 2014 and n = 75, 2019) included personnel from primary health care, home care and long-term care, acute and emergency care, specialty clinics, diabetes-specific programs and private contractors. The proportion of primary care and home care/long-term care (HC/LTC) sites providing screening increased significantly (p < 0.05). A significant increase in the proportion of sites providing assessment for patients designated as moderate risk also increased from 35% (34 out of 96 sites) to 55% (36 out of 65 sites) (p < 0.05), particularly with respect to vascular assessment, and the proportion of sites reporting appropriate follow-up intervals according to the pathway recommendation was also improved. Conclusion Provision of a clinical pathway for diabetic foot care along with education and resources led to increased screening in primary care and HC/LTC settings in Alberta, Canada. HRFT provided primary healthcare providers with an important option for referral and also provided increased expertise for procedures such as vascular assessment for patients with moderate risk of ulceration. This comprehensive model has the potential to reduce progression of foot problems and overall health services utilization. Further analyses of outcomes such as incident lower limb amputation and long-term cost-effectiveness of pathway implementation are underway

    Calcium-Dependent Interaction of Calmodulin with Human 80S Ribosomes and Polyribosomes

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    Ribosomes are the protein factories of every living cell. The process of protein translation is highly complex and tightly regulated by a large number of diverse RNAs and proteins. Earlier studies indicate that Ca<sup>2+</sup> plays a role in protein translation. Calmodulin (CaM), a ubiquitous Ca<sup>2+</sup>-binding protein, regulates a large number of proteins participating in many signaling pathways. Several 40S and 60S ribosomal proteins have been identified to interact with CaM, and here, we report that CaM binds with high affinity to 80S ribosomes and polyribosomes in a Ca<sup>2+</sup>-dependent manner. No binding is observed in buffer with 6 mM Mg<sup>2+</sup> and 1 mM EGTA that chelates Ca<sup>2+</sup>, suggesting high specificity of the CaM–ribosome interaction dependent on the Ca<sup>2+</sup> induced conformational change of CaM. The interactions between CaM and ribosomes are inhibited by synthetic peptides comprising putative CaM-binding sites in ribosomal proteins S2 and L14. Using a cell-free <i>in vitro</i> translation system, we further found that these synthetic peptides are potent inhibitors of protein synthesis. Our results identify an involvement of CaM in the translational activity of ribosomes
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