Diabetes Related Deaths in a Tertiary Pediatric Referral Institution in England: The Value of Biochemical Analyses in Post-Mortem Samples.

OBJECTIVES: To establish the incidence of "diabetes-related death" (DRD) in children with known and unknown Diabetes Mellitus (DM) dying unexpectedly, and describe post-mortem (PM) biochemistry findings. PATIENTS AND METHODS: PM reports from the previous 16-year period were reviewed. Cases of DRD were extracted. All available demographic, clinical, and autopsy data including laboratory analyses was retrieved. RESULTS: 9/1376 (0.7%) DRD cases were identified. This was attributed to Diabetic Ketoacidosis in 7 and to Death in Bed Syndrome in 2. 4/9 cases were known diabetic and on insulin; whilst in 5/9 cases the diagnosis of DM was at PM. The mean age was 11.6 years (range 2.5-15). At PM, 4 cases were undernourished. The histology demonstrated pancreatic changes in keeping with DM in 3/9 and unremarkable pancreatic findings in 6/9. 3 cases also had autoimmune thyroiditis (1 also had myocarditis and Armanni-Ebstein nephropathy). Toxicological and biochemical analysis showed raised: ß-hydroxybutyrate in 6, ketone bodies in 5 cases and raised HbA1c in 3c. CONCLUSION: Type 1 DM is an infrequent but yet potentially preventable cause of death in children. Our findings highlight the value of routine biochemical and toxicological analysis in all PM examinations of infants and children dying suddenly and unexpectedly.

Exposure to High-Fat Style Diet Induced Renal and Liver Structural Changes, Lipid Accumulation and Inflammation in Intact and Ovariectomized Female Rats.

PURPOSE: We hypothesized that low estrogen levels aggravate obesity-related complications. Diet-induced obesity can cause distinct pathologies, including impaired glucose tolerance, inflammation, and organ injury that leads to fatty liver and chronic kidney diseases. To test this hypothesis, ovariectomized (OVX) rats were fed a high-fat style diet (HFSD), and we examined structural changes and inflammatory response in the kidney and liver. METHODS: Sprague-Dawley female rats were ovariectomized or sham-operated and divided into four groups: sham-operated rats fed a normal diet (ND); ovariectomized rats fed a normal diet (OVX-ND); sham-operated rats fed a HFSD; ovariectomized rats fed a high-fat style diet (OVX-HFSD). Mean blood pressure and fasting blood glucose were measured on weeks 0 and 10. The rats were sacrificed 10 weeks after initiation of ND or HFSD, the kidney and liver were harvested for histological, immunohistochemical and immunofluorescence studies. RESULTS: HFSD-fed rats presented a significantly greater adiposity index compared to their ND counterparts. Liver index, fasting blood glucose and mean blood pressure was increased in OVX-HFSD rats compared to HFSD rats at study terminal. Histological and morphometric studies showed focal interstitial mononuclear cell infiltration in the kidney of HFSD rats with mesangial expansion being greater in the OVX-HFSD rats. Both HFSD fed groups showed increased expressions of renal inflammatory markers, namely TNF-alpha, IL-6 and MCP-1, and infiltrating M1 macrophages with some influence of ovarian hormonal status. HFSD-feeding also caused hepatocellular steatosis which was aggravated in ovariectomized rats fed the same diet. Furthermore, hepatocellular ballooning was observed only in the OVX-HFSD rats. Similarly, HFSD-fed rats showed increased expressions of the inflammatory markers and M1 macrophage infiltration in the liver; however, only IL-6 expression was magnified in the OVX-HFSD. CONCLUSION: Our data suggest that some of the structural changes and inflammatory response in the kidney and liver of rats fed a HFSD are exacerbated by ovariectomy.

MicroRNA expression in antiphospholipid syndrome: a systematic review and microRNA target genes analysis

Antiphospholipid antibodies (aPL) are autoantibodies that attack phospholipid through anti-beta 2-glycoprotein 1. The actions of aPL are associated with events leading to thrombosis and morbidity in pregnancy. Antiphospholipid syndrome (APS) is diagnosed when a patient is persistently positive for aPL and also has recognised clinical manifestations such as recurrent pregnancy losses, arterial or venous thrombosis and in a catastrophic case, can result in death. Unfortunately, the pathogenesis of APS is still not well established. Recently, microRNA expressed in many types of diseased tissues were claimed to be involved in the pathological progression of diseases and has become a useful biomarker to indicate diseases, including APS. Objective: This systematic review aims to search for research papers that are focussing on microRNA expression profiles in APS. Method: Three search engines (Ebcohost, ProQuest and Ovid) were used to identify papers related to expression of specific microRNA in antiphospholipid syndrome. Results and Discussion: A total of 357 papers were found and screened, out of which only one study fulfilled the requirement. In this particular study blood samples from APS patients were tested. The microRNAs found to be related to APS were miR-19b and miR-20a. No data was found on specific microRNA being expressed in obstetric antiphospholipid syndrome. Analysis on the microRNA target genes revealed that most genes targeted by miR-19b and miR-20a involve in TGF-Beta Signalling and VEGF, hypoxia and angiogenesis pathways. Conclusion: In view of the limited data on the expressions of microRNA in APS we recommend further research into this field. Characterization of microRNA profile in blood as well as in placenta tissue of patients with APS could be useful in identifying microRNAs involved in obstetric APS.