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We have deployed a multi-omics approach in large cohorts of patients with existing type 2 diabetes to identify biomarkers for disease progression across three molecular classes, metabolites, lipids and proteins. A Cox regression analysis for association with time to insulin requirement in 2,973 patients in the DCS, ANDIS and GoDARTS cohorts identified homocitrulline, isoleucine and 2-aminoadipic acid, as well as the bile acids glycocholic and taurocholic acids, as predictive of more rapid deterioration. Increased levels of eight triacylglycerol species, and lowered levels of the sphingomyelin SM 42:2;2 were also predictive of disease progression. Of ∼1,300 proteins examined in two cohorts, levels of GDF-15/MIC1, IL-18RA, CRELD1, NogoR, FAS, and ENPP7 were associated with faster progression, whilst SMAC/DIABLO, COTL1, SPOCK1 and HEMK2 predicted lower progression rates. Strikingly, identified proteins and lipids were also associated with diabetes incidence and prevalence in external replication cohorts. Implicating roles in disease compensation, NogoR/RTN4R improved glucose tolerance in high fat-fed mice and tended to improved insulin signalling in liver cells whilst IL-18R antagonised inflammatory IL-18 signalling towards nuclear factor kappa-B in vitro. Conversely, high NogoR levels led to islet cell apoptosis. This comprehensive, multi-disciplinary approach thus identifies novel biomarkers with potential prognostic utility, provides evidence for new disease mechanisms, and identifies potential therapeutic avenues to slow diabetes progression.

BackgroundAcute gastrointestinal bleeding (GIB) is a common gastroenterological emergency worldwide with significant morbidity and mortality of 6 per cent-14 per cent. The main causes of death in patients with GIB include shock, aspiration, and therapeutic procedure carried out for the management of the GIB. Thus, the resuscitation strategy of blood transfusion plays a very important role in these patients before any other specific treatment. Currently, endoscopy is considered the mainstay of diagnosis and treatment for patients with GIB. AimsTo assess the effect of an early endoscopic intervention on the need for blood transfusion in patients presented with GIB. MethodsWe retrospectively analysed the data for patients presented with hematemesis, melena, or haematochezia, from July 2015 to July 2016, in Ballarat Base Hospital (BHS) in Victoria, Australia. Data were extracted from the hospital coding system related to patient's demographic history, alcohol intake, comorbidity, procedure details including the timing and the type of procedure performed, and the number of units of blood transfused. Additionally, the laboratory blood test results for each patient were examined through the electronic records to assess the haemoglobin level before and after the blood transfusion.[AMJ 2019;12(2):56-62] of cost of treatment from blood transfusion can be achieved by adopting an optimized restrictive transfusion strategy. What this study adds:1. What is known about this subject? Most guidelines recommend performing endoscopic procedures within 24 hours of acute GI bleeding. What new information is offered in this study?This study assesses the time to perform an endoscopic procedure in patients presenting with acute GIB in relation to the need for blood transfusion. There is a trend towards having more blood transfusion with delayed endoscopic procedure (>12 hours). What are the implications for research, policy, or practice?More prospective studies are needed to further assess the role of early endoscopic intervention in patients with acute GIB.

In the present study the length-weight relationship and condition factor of L.bata (Labeo bata) had been investigated and elucidated with particular reference to the growth status and condition factor in hill stream of Ranikot at District Jamshoro Sindh-Pakistan. A total of 291 individuals with their sixteen morphometric traits were analyzed for length-weight relationship, correlation and condition factor. The length-weight relationship, morphometrics and condition factor indicated positive allometric growth and high level of interdependence (0.992-0.887) between morphometric traits. The mean total length 20.7+1.21cm and mean weight 13.85+1.42gm were observed. A strong linear relationship (r=0.975) was observed between total length and weight variables (a=0.3338). The value of regression coefficient (b=2.684) suggests isometric growth in L.bata. The condition (K=0.724) and relative condition factors (kn=0.751) were observed <1.0, that indicated the environmental impact on the fish in hill stream of Ranikot. The findings suggest satisfactory growth and well-being of fish in the surrounding aquatic environment. In further, more hydrological factors might be investigated to know the real impacting factors.

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