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Inhibition with the miR-193b-3p Guards In opposition to Oxidized Low-Density Lipoprotein-Induced HUVECs Harm by simply upregulating ALDH2.
Background The demand for donated human hearts far exceeds the number available. Xenotransplantation of genetically modified porcine organs provides an alternative. In 2000, an Advisory Board of the International Society for Heart and Lung Transplantation set the benchmark for commencing clinical cardiac xenotransplantation as consistent 60% survival of non-human primates after life-supporting porcine heart transplantations. Recently, we reported the stepwise optimization of pig-to-baboon orthotopic cardiac xenotransplantation finally resulting in consistent success, with 4 recipients surviving 90 (n = 2), 182, and 195 days. Here, we report on 4 additional recipients, supporting the efficacy of our procedure. Results The first 2 additional recipients succumbed to porcine cytomegalovirus (PCMV) infections on Days 15 and 27, respectively. In 2 further experiments, PCMV infections were successfully avoided, and 3-months survival was achieved. Throughout all the long-term experiments, heart, liver, and renal functions remained within normal ranges. Post-mortem cardiac diameters were slightly increased when compared with that at the time of transplantation but with no detrimental effect. There were no signs of thrombotic microangiopathy. The current regimen enabled the prolonged survival and function of orthotopic cardiac xenografts in altogether 6 of 8 baboons, of which 4 were now added. These results exceed the threshold set by the Advisory Board of the International Society for Heart and Lung Transplantation. Conclusions The results of our current and previous experimental cardiac xenotransplantations together fulfill for the first time the pre-clinical efficacy suggestions. PCMV-positive donor animals must be avoided.Background Tobacco smoking and diabetes mellitus contribute significantly to the overall health burden and mortality of Australians. We aimed to assess the relationship of smoking with glycemic control, metabolic profile and complications in Australian patients living with diabetes. Methods We analysed the 2011-2017 biennial Australian National Diabetes Audit cross-sectional data. Patients were classified as current, past or never smokers. Linear (or quantile) and logistic regression models were used to assess for associations. Results Data from 15,352 patients were analysed, including 72.2% with type 2 diabetes. Current smokers comprised 13.5% of the study population. Current and past smokers had a median HbA1c that was 0.49% and 0.14% higher than never smokers, respectively, as well as higher triglyceride and lower HDL levels (all p values less then .0001). Compared to never smokers, current smokers had higher odds of severe hypoglycemia and current and past smokers had higher odds of myocardial infarction, stroke, peripheral vascular disease, lower limb amputation, erectile dysfunction and peripheral neuropathy (all p values ≤.001), with no significant change over time. Conclusion When compared to never smokers, current and past smokers had poorer glycemic and lipid control and higher odds of macrovascular and microvascular complications. Despite this, current smoking remains prevalent among Australians with diabetes.Objective To evaluate the association between glycemic control (hemoglobin A1C, fasting glucose, and random glucose) and the outcomes of wound healing and lower extremity amputation (LEA) among patients with diabetic foot ulcers (DFUs). Research design and methods Medline, EMBASE, Cochrane Library, and Scopus were searched for observational studies published up to March 2019. Five independent reviewers assessed in duplicate the eligibility of each study based on predefined eligibility criteria and two independent reviewers assessed risk of bias. Ameta-analysis was performed to calculate a pooled odds ratio (OR) or hazard ratio (HR) using random effects for glycemic measures in relation to the outcomes of wound healing and LEA. Subgroup analyses were conducted to explore potential source of heterogeneity between studies. The study protocol is registered with PROSPERO (CRD42018096842). Results Of 4572 study records screened, 60 observational studies met the study eligibility criteria of which 47 studies had appropriate data for inclusion in one or more meta-analyses(n = 12,604 DFUs). JNJ26481585 For cohort studies comparing A1C >7.0 to 7.5% vs. lower A1C levels, the pooled OR for LEA was 2.04 (95% CI, 0.91, 4.57) and for studies comparing A1C ≥ 8% vs. less then 8%, the pooled OR for LEA was 4.80 (95% CI 2.83, 8.13). For cohort studies comparing fasting glucose ≥126 vs. less then 126 mg/dl, the pooled OR for LEA was 1.46 (95% CI, 1.02, 2.09). There was no association with A1C category and wound healing (OR or HR). There was high risk of bias with respect to comparability of cohorts as many studies did not adjust for potential confounders in the association between glycemic control and DFU outcomes. Conclusions Our findings suggest that A1C levels ≥8% and fasting glucose levels ≥126 mg/dl are associated with increased likelihood of LEA in patients with DFUs. A purposively designed prospective study is needed to better understand the mechanisms underlying the association between hyperglycemia and LEA.Background Primary hyperparathyroidism is primarily caused by parathyroid adenoma, followed by hyperplasia and parathyroid carcinoma. In the era of minimally invasive, targeted parathyroidectomy, the main challenge remains that of distinguishing intraoperatively pathological parathyroid from normal glands and peri-thyroid fat tissue. The aim of this study is to evaluate the surgical outcomes of a novel minimally invasive technique called ultrasound-guided dye-assisted parathyroidectomy (USDAP). Methods We perform a retrospective analysis of patients affected by parathyroid adenoma, treated with USDAP at our institution between 2014 and 2019. Data were collected on patient age and sex, tumor location and size, preoperative investigations, histopathology, perioperative complications and surgical outcomes. Results Between January 2014 and June 2019, 43 patients underwent parathyroidectomy in our Institute. Each case was discussed by the Institutional Multidisciplinary Board. All patients undergoing thyroidectomy together with USDAP or patients undergoing USDAP under endoscopic control were excluded from the present study.
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