The adipocyte-derived adiponectin hormone bridges obesity and its cardio-metabolic complications. Genetic variants at the ADIPOQ locus, in ADIPOR1 , and ADIPOR2 have been associated with adiponectin concentrations and cardio-metabolic complications in diverse ethnicities. However, no studies have examined these associations in Mexican children. We recruited 1 457 Mexican children from Mexico City. Six genetic variants in or near ADIPOQ (rs182052, rs2241766, rs266729, rs822393), ADIPOR1 (rs10920533), and ADIPOR2 (rs11061971) were genotyped. Associations between serum adiponectin, genetic variants, and cardio-metabolic traits were assessed using linear and logistic regressions adjusted for age, sex, and recruitment center. Serum adiponectin concentration was negatively associated with body mass index, waist to hip ratio, low-density lipoprotein cholesterol, total cholesterol, triglycerides, fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance, dyslipidemia and overweight/obesity status (7.76 × 10 −40 ≤ p ≤ 3.00 × 10 −3 ). No significant associations between genetic variants in ADIPOQ , ADIPOR1 , and ADIPOR2 and serum adiponectin concentration were identified (all p ≥ 0.30). No significant associations between the six genetic variants and cardio-metabolic traits were observed after Bonferroni correction (all p < 6.9 × 10 −4 ). Our study suggests strong associations between circulating adiponectin concentration and cardio-metabolic traits in Mexican children.

Caveolin-1 (cav-1), an integral protein of the membrane microdomains caveolae, is required for synthesis of matrix proteins by glomerular mesangial cells (MC). Previously, we demonstrated that the antifibrotic protein follistatin (FST) is transcriptionally upregulated in cav-1 knockout MC and that its administration is protective against renal fibrosis. Here, we screened cav-1 wild-type and knockout MC for FST-targeting microRNAs in order to identity novel antifibrotic therapeutic targets. We identified that miR299a-5p was significantly suppressed in cav-1 knockout MC, and this was associated with stabilization of the FST 3′UTR. Overexpression and inhibition studies confirmed the role of miR299a-5p in regulating FST expression. Furthermore, the profibrotic cytokine TGFβ1 was found to stimulate the expression of miR299a-5p and, in turn, downregulate FST. Through inhibition of FST, miR299a-5p overexpression augmented, while miR299a-5p inhibition diminished TGFβ1 profibrotic responses, whereas miR299a-5p overexpression re-enabled cav-1 knockout MC to respond to TGFβ1. In vivo, miR299a-5p was upregulated in the kidneys of mice with chronic kidney disease (CKD). miR299a-5p inhibition protected these mice against renal fibrosis and CKD severity. Our data demonstrate that miR299a-5p is an important post-transcriptional regulator of FST, with its upregulation an important pathogenic contributor to renal fibrosis. Thus, miR299a-5p inhibition offers a potential novel therapeutic approach for CKD.

patients (mean age 65 years, mean Deyo-Charlson Comorbidity Index 0.6, mean hospital length of stay 6.35 days); 214 cases and 214 controls were randomly selected from the cohort for chart data analysis. In the 12 months post-index arthroplasty, there were 830 (2.5%) patients who had SSI, 644 (1.9%) who had SSB, and 84 (0.3%) who developed VTE. Of all SSI events, 65% occurred by 90 days following arthroplasty. Significantly more patients who had received post-discharge thromboprophylaxis versus those that did not developed SSI but not SSB (SSI: 28.4% vs 23.2% [PϽ0.0001]; SSB:28.5% vs 23.3% [Pϭ0.07]). In the logistic regression analysis, only the duration of surgery (Pϭ0.004), surgical revision (Pϭ0.04), and rehospitalization (PϽ0.001) emerged as independent predictors of SSI. CONCLUSIONS: Postdischarge thromboprophylaxis and SSB were not associated with post-operative SSI, thus dispelling concerns about the increased risk of developing SSI due to prolonged SSB associated with the use of pharmacologic thromboprophylaxis. Additional studies are needed to endorse these findings in similar patient populations. OBJECTIVES:The risk of post-discharge venous thromboembolism (VTE) and bleeding in total knee and hip arthroplasty (TKA/THA) has not been completely elucidated because interventions to reduce these adverse outcomes have evolved rapidly. The objective of this study was to determine the incidence of these events and associated risk factors, and to evaluate the use of thromboprophylaxis. METHODS: Administrative medical records (2004 -2009) from a large healthcare plan were linked to an inpatient database of 450 hospitals in the United States. Adult patients undergoing TKA or THA with no evidence of prior orthopaedic surgeries, prior VTE, post-discharge revision surgeries, or death were included. ICD-9-CM diagnosis and CPT/HCPC procedure codes were used for evaluating symptomatic VTE and bleeding rates 90 days post-surgery. Multivariate analyses were performed to identify predictors of VTE and bleeding after hospitalization. RESULTS: Two hundred twenty-six of 9167 patients (2.5%; 3109 THA, 6058 TKA) with a median age of 60 years and a mean Charlson-Quan comorbidity index score of 0.5 experienced VTE, and 324 (3.5%) had bleeding. Most of these events occurred post-discharge (70% and 79%, respectively). Over 50% of VTE occurred within 30 days post-discharge. Consistent predictors of VTE and bleeding after hospitalization were inpatient VTE or bleeding, respectively, and all-cause rehospitalization. Post-discharge thromboprophylaxis was not a significant risk factor for bleeding. Ninety-eight percent of patients received thromboprophylaxis during hospitalization; 26% received it post-discharge. During hospitalization, three-fourths of patients received enoxaparin and/or warfarin, often in combination with mechanical prophylaxis devices (57%). Post-discharge, mean antithrombotic drug exposure was 7.4 days. CONCLUSIONS: Patients who experience VTE or bleeding during hospitalization and patients who are rehospitalized are...