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Almost 40% of adults worldwide are classified as overweight or obese. Exercise is a beneficial intervention in obesity, partly due to increases in mitochondrial activity and subsequent increases in nicotinamide adenine dinucleotide (NAD+), an important metabolic cofactor. Recent studies have shown that increasing NAD+ levels through pharmacological supplementation with precursors such as nicotinamide mononucleotide (NMN) improved metabolic health in high-fat-diet (HFD)-fed mice. However, the effects of combined exercise and NMN supplementation are unknown. Thus, here we examined the combined effects of NMN and treadmill exercise in female mice with established obesity after 10 wk of diet. Five-week-old female C57BL/6J mice were exposed to a control diet (n = 16) or HFD. Mice fed a HFD were either untreated (HFD; n = 16), received NMN in drinking water (400 mg/kg; HNMN; n = 16), were exposed to treadmill exercise 6 days/wk (HEx; n = 16), or were exposed to exercise combined with NMN (HNEx; n = 16). Although some metabolic benefits of NMN have been described, at this dose, NMN administration impaired several aspects of exercise-induced benefits in obese mice, including glucose tolerance, glucose-stimulated insulin secretion from islets, and hepatic triglyceride accumulation. HNEx mice also exhibited increased antioxidant and reduced prooxidant gene expression in both islets and muscle, suggesting that altered redox status is associated with the loss of exercise-induced health benefits with NMN cotreatment. Our data show that NMN treatment impedes the beneficial metabolic effects of exercise in a mouse model of diet-induced obesity in association with disturbances in redox metabolism.NEW & NOTEWORTHY NMN dampened exercise-induced benefits on glucose handling in diet-induced obesity. click here NMN administration alongside treadmill exercise enhanced the ratio of antioxidants to prooxidants. We suggest that NMN administration may not be beneficial when NAD+ levels are replete.
The bladder cuff management and its surgical approach represent an essential and debated step in radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). The objective of our study was to determine which bladder-cuff management has the best oncological outcomes in terms of bladder recurrence-free survival ( BRFS).
We retrospectively analyzed all patients who underwent an open robot-assisted laparoscopic (RNU) or a combined RNU between March 2012 and March 2019 in three academic hospitals. Bladder-cuff management approaches were divided into two categories (O-cuff) open bladder cuff and (R-cuff) robot-assisted bladder cuff. We assessed demographic characteristics, distal ureter approach, pathology, and operative details as well as oncological outcomes including BRFS. Survival was analysed using the Kaplan-Meier method and compared using the log-rank test. A multivariable analysis was performed to identify predictive factors of bladder recurrence.
A total of 117 patients were includeddifference in BRFS between the O-cuff and R-cuff groups. Nevertheless, we underlined that distal ureter tumor was associated with bladder recurrence. Although we did not find differences regarding the surgical approach, bladder-cuff remains a very important step of RNU and caution should be taken when performed laparoscopically to avoid any tumor spillage. Risk factors for bladder cancer recurrence might be taken into account for the choice of its surgical approach. .
Oxidative stress is a characteristic of many systemic diseases associated with thrombosis. Thiol isomerases are a family of oxidoreductases important in protein folding and are exquisitely sensitive to the redox environment. They are essential for thrombus formation and represent a previously unrecognized layer of control of the thrombotic process. Yet the mechanisms by which thiol isomerases function in thrombus formation is unknown. Recent Advances The oxidoreductase activity of thiol isomerase in thrombus formation is controlled by the redox environment via oxidative changes to active site cysteines. Specific alterations can now be detected owing to advances in the chemical biology of oxidative cysteine modifications.
Understanding of the role of thiol isomerases in thrombus formation has focused largely on identifying single disulfide bond modifications in isolated proteins (e.g., αIIbβ3, tissue factor, vitronectin, or GPIbα). An alternative approach is to conceptualize thiol isomerases as effectors in redox signaling pathways that control thrombotic potential by modifying substrate networks.
Cysteine-based chemical biology will be employed to study thiol-dependent dynamics mediated by the redox state of thiol isomerases at the systems level. This approach could identify thiol isomerase-dependent modifications of the disulfide landscape that are prothrombotic.
Cysteine-based chemical biology will be employed to study thiol-dependent dynamics mediated by the redox state of thiol isomerases at the systems level. This approach could identify thiol isomerase-dependent modifications of the disulfide landscape that are prothrombotic.Introduction The proportion of robotic procedures continues to rise. The literature reinforces that robotic procedures take longer and are often more costly. We compared cost and peri-operative outcomes of laparoscopic radical nephrectomy (LRN) and robotic assisted radical nephrectomy (RARN) at our high-volume center. Methods We retrospectively reviewed our 2012-2015 data repository for patients undergoing RARN and LRN for a renal mass. Peri-operative and oncologic outcomes were compared. We performed a multivariate analysis of operative time, estimated blood loss, length of stay, overall and major 90-day complication rate while controlling for demographic data, Charlson Comorbidity Index (CCI), tumor size, and surgeon factors. We compared fixed, variable and distinct procedural costs. Results We identified 99 LRN and 95 RARN cases. There was no difference in demographic data, tumor size, preoperative renal function, and malignant histology. LRN had more comorbidities (49.5% vs 27.3% CCI 2+, p=0.018). Mean preoperative GFR was higher in the robotic cohort (84.
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