Risk assessment of Pakistani individuals for diabetes (RAPID)

ObjectiveTo develop and evaluate a risk score to predict people at high risk of developing type 2 diabetes in Pakistan.MethodologyCross sectional data regarding primary prevention of diabetes in Pakistan. Diabetes risk score was developed by using simple parameters namely age, waist circumference, and family history of diabetes. Odds ratios of the model were used to assign a score value for each variable and the diabetes risk score was calculated as the sum of those scores.ResultsWe externally validated the score using two data from 1264 subjects and 856 subjects aged 25 years and above from two separate studies respectively. Validating this score using the first data from the second screening study gave an area under the receive operator characteristics curve [AROC] of 0.758. A cut point of 4 had a sensitivity of 47.0% and specificity of 88% and in the second data AROC is 0.7 with 44% sensitivity and 89% specificity.ConclusionsA simple diabetes risk score, based on a set of variables can be used for the identification of high risk individuals for early intervention to delay or prevent type 2 diabetes in Pakistani population.     

Modulation of ENaC,CFTR, and iNOS expression in bronchial epithelial cells after stimulation with Staphylococcus epidermidis (94B080) and Staphylococcus aureus (90B083)

Bacteria affect the respiratory epithelium, which is covered by airway surface liquid (ASL) and mucus. Ion concentrations in the ASL are determined by the cystic fibrosis transmembrane conductance regulator (CFTR) and the epithelial Na⁺ channel (ENaC). Neonatal sepsis is a major risk factor for subsequent pulmonary disease in preterm newborns. Predominating are coagulase‐negative staphylococci (e.g., Staphylococccus epidermidis and Staphylococccus aureus). The aim of this study was to investigate modulation of CFTR, ENaC, mucins, proinflammatory cytokines, and inducible nitric oxide synthase (iNOS) in respiratory epithelial cells after S. epidermidis 94B080 and S. aureus 90B083 exposure. Bronchial epithelial cells were incubated with S. epidermidis 94B080 and S. aureus 90B083 (neonatal blood isolates) for 1–36 h. Expression of CFTR, ENaC, iNOS, and mucins was analyzed by real‐time PCR and Western blotting. Release of cytokines was analyzed by ELISA, and production of NO by the Griess assay. Expression of CFTR significantly decreased after 36 h incubation with S. epidermidis and more prominently with S. aureus, whereas S. epidermidis caused a significant increase in the expression of β‐ and γ‐ENaC. Expression of iNOS increased, but NO was not detected. Both staphylococci caused a decrease in the intracellular Ca²⁺ concentration. S. aureus induced increased secretion of IL‐6, IL‐8, and transforming nuclear factor (TNF)‐α in a time‐dependent manner as compared with S. epidermidis. In conclusion, expression of ENaC, CFTR, and iNOS is modulated by exposure to S. aureus 90B083 and S. epidermidis 94B080. S. aureus is more potent in causing release of IL‐6, IL‐8, and TNF‐α by bronchial epithelial cells as compared with S. epidermidis. The mRNA expression for the mucus proteins MUC2, MUC5AC, and MUC5B could not be measured, neither in the presence nor in the absence of bacteria.     

Neonatal Liver Disease Associated with Placental Transfer of Anti-mitochondrial Antibodies

Background: Anti-mitochondrial antibody is the diagnostic hallmark of primary biliary cirrhosis. Its role in the aetiology of primary biliary cirrhosis is controversial. Methods: Two cases of neonatal hepatitis seropositive for anti-mitochondrial antibody are described. Anti-mitochondrial antibody Ig isotype and epitopic specificity were investigated by immunofluorescence and enzyme immunoassays. Results: In both infants anti-mitochondrial antibody was of the G class, mainly G1 and G3 subclasses, and reacted with two synthetic peptides reproducing major M2 epitopic regions: inner lipoyl domain pyruvate dehydrogenase complex (PDC)-E2_162-176 and PDC-E3 binding protein (PDC-E3BP)_86-100. One infant also reacted with outer lipoyl domain PDC-E2_35-49, and 2-oxoglutarate dehydrogenase complex (OGDC)-E2_99-113. An identical pattern of reactivity was present in their mothers, indicating the maternal origin of the antibodies. Anti-mitochondrial antibody disappeared in the infants with the disappearance of the liver pathology. Conclusions: The simultaneous disappearance of hepatitis and anti-mitochondrial antibody in the infants suggests a possible causal link between the two.