Function of specialized regulatory proteins and signaling pathways in exercise-induced muscle mitochondrial biogenesis

AbstractSkeletal muscle mitochondrial content and function are regulated by a number of specialized molecular pathways that remain to be fully defined. Although a number of proteins have been identified to be important for the maintenance of mitochondria in quiescent muscle, the requirement for these appears to decrease with the activation of multiple overlapping signaling events that are triggered by exercise. This makes exercise a valuable therapeutic tool for the treatment of mitochondrially based metabolic disorders. In this review, we summarize some of the traditional and more recently appreciated pathways that are involved in mitochondrial biogenesis in muscle, particularly during exercise

Access to Care and Outcomes for Neuroendocrine Tumours: Does Socioeconomic Status Matter?

Introduction: Neuroendocrine tumours (NETS) are a poorly understood malignancy lacking standardized care. Differences in socioeconomic status (SES) might worsen the effect of non-standardized care. We examined the effect of SES on NET peri-diagnostic care patterns and outcomes. Methods: In this population-based cohort study, NET cases identified from a provincial cancer registry (1994–2009) were divided into low (1st and 2nd income quintiles) and high (3rd, 4th, and 5th quintiles) SES groups. We compared peri-diagnostic health care utilization (–2 years to +6 months), metastatic recurrence, and overall survival (os) between the groups. Results: Of 4966 NET patients, 38.3% had a low SES. Neither the primary NET sites (p = 0.15), nor the metastatic presentation (p = 0.31) differed. Patients with low SES had a higher mean number of physician visits (20.1 ± 19.9 vs. 18.1 ± 16.5, p = 0.001) and imaging studies (56 ± 50 vs. 52 ± 44, p = 0.009) leading to the NET diagnosis. Rates of primary tumour resection (p = 0.14), hepatectomy (p = 0.45), systemic therapy (p = 0.38), and liver embolization (p = 0.13) did not differ with SES. In the low-SES group, metastatic recurrence was more likely (41.1% vs. 37.6%, p = 0.01) during a median follow-up of 61.7 months, and the 10-year os was inferior (47.1% vs. 52.2%, p < 0.01). Low SES was associated with worse os (hazard ratio: 1.16; 95% confidence interval: 1.06 to 1.26) after adjustment for age, sex, comorbidity burden, primary NET site, and rural living. Conclusions: Low SES was associated with more physician visits and imaging before a NET diagnosis, but not with more advanced stage at presentation nor with an effect on the pattern of therapy. Long-term outcomes were inferior in the low-SES group. These data can help to inform the design of health care delivery for NETS

Critical appraisal of predictive tools to assess the difficulty of laparoscopic liver resection: a systematic review

BACKGROUND: Objective assessment of the difficulty of laparoscopic liver resection (LLR) preoperatively is key in improving its uptake. Difficulty scores are proposed but are not used routinely in practice. We identified and appraised predictive models to estimate LLR difficulty. METHODS: We systematically searched the literature for tools predicting LLR difficulty. Two independent reviewers selected studies, abstracted data and assessed methodology. We evaluated tools' quality and clinical relevance using the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) guidelines. RESULTS: From 1037 citations, we included 8 studies reporting on 4 predictive tools using data from 1995 to 2016 in Asia and Europe. In 4 development studies, tools were designed to predict difficulty as assigned by experts using a 10-level difficulty index, operative time, post-operative morbidity or intra-operative complications. Internal validation and performance metrics were reported in one development study. One tool was subjected to external validations in 4 studies (1 independent and geographic). Validations compared post-operative outcomes (operative time, blood loss, transfusion, major morbidity and conversion) between the risk categories. One study validated discrimination (AUROC 0.53). Calibration was not assessed. CONCLUSION: Existing tools cannot be used confidently to predict LLR difficulty. Consistent objective clinical outcomes to predict to define LLR difficulty should be established, and better-quality tools developed and validated in a wide array of populations and clinical settings, following best practices for predictive tools development and validation. This will improve risk stratification for future trials and uptake of LLR