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Diabetic kidney disease (DKD) represents a major global health problem. Accelerated ageing is a key feature of DKD and, therefore, characteristics of accelerated ageing may provide useful biomarkers or therapeutic targets. Harnessing multi-omics, features affecting telomere biology and any associated methylome dysregulation in DKD were explored. Genotype data for nuclear genome polymorphisms in telomere-related genes were extracted from genome-wide case–control association data (n = 823 DKD/903 controls; n = 247 end-stage kidney disease (ESKD)/1479 controls). Telomere length was established using quantitative polymerase chain reaction. Quantitative methylation values for 1091 CpG sites in telomere-related genes were extracted from epigenome-wide case–control association data (n = 150 DKD/100 controls). Telomere length was significantly shorter in older age groups (p = 7.6 × 10−6). Telomere length was also significantly reduced (p = 6.6 × 10−5) in DKD versus control individuals, with significance remaining after covariate adjustment (p = 0.028). DKD and ESKD were nominally associated with telomere-related genetic variation, with Mendelian randomisation highlighting no significant association between genetically predicted telomere length and kidney disease. A total of 496 CpG sites in 212 genes reached epigenome-wide significance (p ≤ 10−8) for DKD association, and 412 CpG sites in 193 genes for ESKD. Functional prediction revealed differentially methylated genes were enriched for Wnt signalling involvement. Harnessing previously published RNA-sequencing datasets, potential targets where epigenetic dysregulation may result in altered gene expression were revealed, useful as potential diagnostic and therapeutic targets for intervention.

BackgroundGeneral practitioners (GPs) need robust, up-to-date evidence to deliver high-quality patient care. There is limited literature regarding the role of international GP professional organizations in developing and publishing clinical guidelines to support GPs clinical decision making.ObjectiveTo identify evidence-based guidance and clinical guidelines produced by GP professional organizations and summarize their content, structure, and methods of development and dissemination.MethodsScoping review of GP professional organizations following Joanna Briggs Institute guidance. Four databases were searched and a grey literature search was conducted. Studies were included if they were: (i) evidence-based guidance documents or clinical guidelines produced de novo by a national GP professional organization, (ii) developed to support GPs clinical care, and (iii) published in the last 10 years. GP professional organizations were contacted to provide supplementary information. A narrative synthesis was performed.ResultsSix GP professional organizations and 60 guidelines were included. The most common de novo guideline topics were mental health, cardiovascular disease, neurology, pregnancy and women’s health and preventive care. All guidelines were developed using a standard evidence-synthesis method. All included documents were disseminated through downloadable pdfs and peer review publications. GP professional organizations indicated that they generally collaborate with or endorse guidelines developed by national or international guideline producing bodies.ConclusionThe findings of this scoping review provide an overview of de novo guideline development by GP professional organizations and can support collaboration between GP organizations worldwide thus reducing duplication of effort, facilitating reproducibility, and identifying areas of standardization.Protocol registrationOpen Science Framework: https://doi.org/10.17605/OSF.IO/JXQ26.

The prevalence of diabetes is increasing globally, and this trend is predicted to continue for future decades. Research is needed to uncover new ways to manage diabetes and its co-morbidities. A significant secondary complication of diabetes is kidney disease, which can ultimately result in the need for renal replacement therapy, via dialysis or transplantation. Diabetic kidney disease presents a substantial burden to patients, their families and global healthcare services. This review highlights studies that have harnessed genomic, epigenomic and functional prediction tools to uncover novel genes and pathways associated with DKD that are useful for the identification of therapeutic targets or novel biomarkers for risk stratification. Telomere length regulation is a specific pathway gaining attention recently because of its association with DKD. Researchers are employing both observational and genetics-based studies to identify telomere-related genes associated with kidney function decline in diabetes. Studies have also uncovered novel functions for telomere-related genes beyond the immediate regulation of telomere length, such as transcriptional regulation and inflammation. This review summarises studies that have revealed the potential to harness therapeutics that modulate telomere length, or the associated epigenetic modifications, for the treatment of DKD, to potentially slow renal function decline and reduce the global burden of this disease.

Introduction: Reflection is thought to be an essential skill for physicians. Although much has been written about it, there is little concurrence about how to best teach reflection in medical education. The aim of this review was to determine: (i) which educational interventions are being used to develop reflection, (ii) how is reflection being assessed, and (iii) what are the most effective interventions. Methods: Inclusion criteria comprised: (i) undergraduate medical students, (ii) a teaching intervention to develop reflection, and (iii) assessment of the intervention. A review protocol was developed and nine databases were searched. Screening, data extraction, and analysis procedures were performed in duplicate. Due to the heterogeneity of studies, a narrative synthesis approach was performed for the study analysis. Results: Twenty-eight studies met the inclusion criteria. The interventions in these studies had at least of two of the following components related to reflection: (i) introduction, (ii) trigger, (iii) writing, (iv) guidelines, (v) small group discussion, (vi) tutor and (vii) feedback. Three validated rubrics were used to assess reflective writing in these studies. Conclusions: The strongest evidence from studies in this review indicates that guidelines for, and feedback on, reflective writing improve student reflection.

Multiple genetic strategies are available to help improve understanding of diabetic nephropathy. This methods chapter provides an overview of phenotype considerations specific to diabetic nephropathy and biobank essentials, and provides detailed methodology for a common benchtop wet-lab approach (Ion Torrent semiconductor sequencing) including in silico genetic variant identification from next-generation sequencing data to identify genetic risk factors for diabetic nephropathy.

The aim of this study was to determine whether mutations in mitochondrial DNA play a role in high-pressure primary open-angle glaucoma (OMIM 137760) by analyzing new data from massively parallel sequencing of mitochondrial DNA.Glaucoma patients with high-tension primary open-angle glaucoma and ethnically matched and age-matched control subjects without glaucoma were recruited. The entire human mitochondrial genome was amplified in two overlapping fragments by long-range polymerase chain reaction and used as a template for massively parallel sequencing on an Ion Torrent Personal Genome Machine. All variants were confirmed by conventional Sanger sequencing.Whole-mitochondrial genome sequencing was performed in 32 patients with primary open-angle glaucoma from India (n = 16) and Ireland (n = 16). In 16 of the 32 patients with primary open-angle glaucoma (50% of cases), there were 22 mitochondrial DNA mutations consisting of 7 novel mutations and 8 previously reported disease-associated sequence variants. Eight of 22 (36.4%) of the mitochondrial DNA mutations were in complex I mitochondrial genes.Massively parallel sequencing using the Ion Torrent Personal Genome Machine with confirmation by Sanger sequencing detected a pathogenic mitochondrial DNA mutation in 50% of the primary open-angle glaucoma cohort. Our findings support the emerging concept that mitochondrial dysfunction results in the development of glaucoma and, more specifically, that complex I defects play a significant role in primary open-angle glaucoma pathogenesis.

The global prevalence of diabetic nephropathy is rising in parallel with the increasing incidence of diabetes in most countries. Unfortunately, up to 40 % of persons diagnosed with diabetes may develop kidney complications. Diabetic nephropathy is associated with substantially increased risks of cardiovascular disease and premature mortality. An inherited susceptibility to diabetic nephropathy exists, and progress is being made unravelling the genetic basis for nephropathy thanks to international research collaborations, shared biological resources and new analytical approaches. Multiple epidemiological studies have highlighted the clinical heterogeneity of nephropathy and the need for better phenotyping to help define important subgroups for analysis and increase the power of genetic studies. Collaborative genome-wide association studies for nephropathy have reported unique genes, highlighted novel biological pathways and suggested new disease mechanisms, but progress towards clinically relevant risk prediction models for diabetic nephropathy has been slow. This review summarises the current status, recent developments and ongoing challenges elucidating the genetics of diabetic nephropathy.

Chronic kidney disease (CKD) has become a serious public health problem because of its associated morbidity, premature mortality, and attendant healthcare costs. The rising number of persons with CKD is linked with the aging population structure and an increased prevalence of diabetes, hypertension, and obesity. There is an inherited risk associated with developing CKD, as evidenced by familial clustering and differing prevalence rates across ethnic groups. Previous studies to determine the inherited risk factors for CKD rarely identified genetic variants that were robustly replicated. However, improvements in genotyping technologies and analytic methods are now helping to identify promising genetic loci aided by international collaboration and multiconsortia efforts. More recently, epigenetic modifications have been proposed to play a role in both the inherited susceptibility to CKD and, importantly, to explain how the environment dynamically interacts with the genome to alter an individual's disease risk. Genome-wide, epigenome-wide, and whole transcriptome studies have been performed, and optimal approaches for integrative analysis are being developed. This review summarizes recent research and the current status of genetic and epigenetic risk factors influencing CKD using population-based information.