Type-2 Diabetes Mellitus (T2DM) is presently the fastest growing disease and has been recognized to be caused by a collision between inherited parental genes and the environment. The current prevalence in Pakistan of type-2 diabetes mellitus is 26.3%. Out of them 19.2% had disease two to three decades back while 7.1% are recently diagnosed cases. Worldwide burden of disease was 415 million in 2015 and this number will increase to 642 million by 2040. Parental history of diabetes mellitus is a chief reason for the development of T2DM in children, but whether this association derives from shared genetic or environmental factors is unclear. Persistent high blood glucose levels can result in drastic outcomes like Diabetic Ketoacidosis and Hyperosmolar non ketotic syndrome. Genome-wide association analyses have uncovered multiple genomic regions associated with T2DM, but identification of the causal variants remains a challenge. This review will discuss the approach of diagnosing T2DM by analyzing the association of gene variants and family history.
<abstract><sec> <title>Objective</title> <p>The aim of the current study was to explore the gene enrichment and dysregulated pathways on the basis of interaction network analysis of <italic>SLC30A8</italic> in type 1 diabetes mellitus (T1DM). <italic>SLC30A8</italic> polymorphism could be characterized as a beneficial tool to identify the interacting gene in developing T1DM.</p> </sec><sec> <title>Materials and methods</title> <p><italic>SLC30A8</italic> interacting protein interaction network was obtained by String Interaction network Version 11.0. Ten proteins were identified interacting with <italic>SLC30A8</italic> and were analysed by protein-protein interaction and enrichment network analysis along with Functional Enrichment analysis tool (FunRich 3.1.3) to map the gene data sets. In entire analysis, FunRich database was used as background against all annotated gene/protein list. Protein-protein interaction (PPI) and enrichment network analysis of the selected protein: <italic>SLC30A8</italic> gene along with gene mapping and pathway enrichment were performed using FunRich 3.1.3 and String Interaction network Version 11.0.</p> </sec><sec> <title>Results</title> <p>Biological pathway grouping displayed enriched proteins in TRAIL signalling pathway (<italic>p</italic> < 0.001). <italic>PTPRN, GAD2</italic> and <italic>TCF7L2</italic> were enriched in TRAIL Signalling pathway when <italic>INS</italic> was made focused gene and directly interacting with <italic>SLC30A8</italic>.</p> </sec><sec> <title>Conclusions</title> <p>TRAIL signalling pathways were enriched in T1DM. Therefore, <italic>SLC30A8</italic> along with <italic>PTPRN, GAD2</italic> and <italic>TCF7L2</italic> involved in TRAIL pathway must be further explored to understand their in vivo role in T1DM.</p> </sec></abstract>
Background Nontuberculous mycobacterium (NTM) is a rare cause of prosthetic joint infection (PJI) following primary total knee arthroplasty (TKA). NTM causes a variety of infections, mainly divided into pulmonary and extrapulmonary infections. In Pakistan, there was a 7.7-fold increase in NTM infections from 21 cases in 2012 to 163 cases in 2018. An earlier study evaluating the distribution of NTM species across Pakistan suggested geographical variation across different regions, every area having its own distribution spectrum. There are no data available especially in developing countries such as Pakistan regarding PJI due to NTM following primary TKA. The purpose of our study was to determine treatment outcomes of two-stage revision surgery following NTM infection. Methods This is a retrospective study. Patients who underwent TKA between June 2008 and December 2018 were included in the study. NTM was defined as the presence of traditional criteria for diagnosing PJI plus growth of NTM cultured from a joint aspirate or deep periprosthetic tissue specimen using Löwenstein-Jensen medium and Mycobacteria Growth Indicator Tube medium. All patients were female with a mean age of 62.8 ± 7.9 years. The mean body mass index was 25.6 ± 2.8 kg/m 2 . Treatment outcomes were categorized into favorable and unfavorable. Results We found rapid-growing mycobacterium in 6 patients whereas slow-growing mycobacterium was found in 2 patients only. Generally, clarithromycin was the standard antibiotic used in all cases of NTM infections. All patients underwent revision surgery. Conclusions Meticulous surgical debridement and prolonged antibiotic treatment course were the only hope of cure to combat the unusual cause of PJI following primary TKA.
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