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The size of the satellite cell pool is reduced in estradiol (E2)-deficient female mice and humans. Here, we use a combination of in vivo and in vitro approaches to identify mechanisms, whereby E2 deficiency impairs satellite cell maintenance. By measuring satellite cell numbers in mice at several early time points postovariectomy (Ovx), we determine that satellite cell numbers decline by 33% between 10 and 14 days post-Ovx in tibialis anterior and gastrocnemius muscles. At 14 days post-Ovx, we demonstrate that satellite cells have a reduced propensity to transition from G0/G1 to S and G2/M phases, compared with cells from ovary-intact mice, associated with changes in two key satellite cell cycle regulators, ccna2 and p16INK4a. Further, freshly isolated satellite cells treated with E2 in vitro have 62% greater cell proliferation and require less time to complete the first division. Using clonal and differentiation assays, we measured 69% larger satellite cell colonies and enhanced satellite cell-derived myoblast differentiation with E2 treatment compared with vehicle-treated cells. Together, these results identify a novel mechanism for preservation of the satellite cell pool by E2 via promotion of satellite cell cycling.

What is the central question of this study? Is 1 week of exercise training sufficient to reduce local and systemic inflammation? Do obesity and short-term concurrent aerobic and resistance exercise training alter skeletal muscle extracellular vesicle (EV) contents? What is the main finding and its importance? Obesity alters skeletal muscle small EV microRNAs targeting inflammatory and growth pathways. Exercise training alters skeletal muscle small EV microRNAs targeting inflammatory pathways, indicative of reduced inflammation. Our findings provide support for the hypotheses that EVs play a vital role in intercellular communication during health and disease and that EVs mediate many of the beneficial effects of exercise.Obesity is associated with chronic inflammation characterized by increased levels of inflammatory cytokines, whereas exercise training reduces inflammation. Small extracellular vesicles (EVs; 30-150 nm) participate in cell-to-cell communication in part through microRNA (miRNA) post-transcriptional regulation of mRNA. We examined whether obesity and concurrent aerobic and resistance exercise training alter skeletal muscle EV miRNA content and inflammatory signalling. Vastus lateralis biopsies were obtained from sedentary individuals with (OB) and without obesity (LN). Before and after 7 days of concurrent aerobic and resistance training, muscle-derived small EV miRNAs and whole-muscle mRNAs were measured. Pathway analysis revealed that obesity alters small EV miRNAs that target inflammatory (SERPINF1, death receptor and Gα

Obesity is associated with numerous changes in skeletal muscle including greater muscle mass and muscle fiber cross sectional area (FCSA), yet fasted muscle protein synthesis is lower. Activation of the IGF-1/Akt/mTOR pathway is critical for muscle mass maintenance, muscle hypertrophy, and muscle protein regulation. Resistance exercise (RE) increases muscle mass, FCSA, and IGF-1. Persons with obesity have greater skeletal muscle mass and larger skeletal muscle fiber cross sectional area. The IGF-1/Akt/mTOR pathway is critical for the regulation of skeletal muscle mass. Our study found men and women with obesity have lower skeletal muscle IGF-1 mRNA and protein and higher expression of miR-206 an epigenetic regulator of IGF-1, at rest and following an acute bout of resistance exercise. Despite this, Akt mediated signaling was maintained and maintenance of phosphorylation does not appear to be accounted for by compensatory pathways. Our findings suggest a possible negative feedback mechanism via increased miR-206 and in turn decreased IGF-1 to limit further skeletal muscle hypertrophy in persons with obesity. The current work investigated if: (1) obesity dysregulates basal skeletal muscle IGF-1 pathways; and (2) obesity augments the muscle IGF-1 pathway responses to acute RE. Eight sedentary (no self-reported physical activity), lean (LN) and eight sedentary subjects with obesity (OB) had vastus lateralis biopsies taken at rest, and 15 min and 3 h post-acute RE for the measurement of the IGF-1 pathway and muscle FCSA. Type II FCSA was larger in OB vs. LN. Skeletal muscle IGF-1 mRNA and IGF-1 protein were lower in OB vs. LN at rest and post-exercise. Acute RE increased IGF-1 protein similarly in both groups. The expression of miR-206, a post-transcriptional inhibitor of IGF-1 expression, was higher in OB vs. LN and linked with lower IGF-1 mRNA (r = – 0.54). In spite of greater muscle FCSA, muscle IGF-1 expression was lower in obesity suggesting negative feedback may be limiting muscle mass expansion in obesity.

What is the central question of this study? Do obesity and acute resistance exercise alter the regulation of muscle intercellular communication pathways consistent with inadequate compensatory angiogenesis in response to muscle loading present in individuals with obesity? What is the main finding and its importance? Obesity is associated with differences in both pro- and anti-angiogenic signalling consistent with lower muscle capillarization. Acute resistance exercise increases the release of skeletal muscle small extracellular vesicles independent of body mass. These results identify new cellular factors associated with impaired angiogenesis in obesity and the positive effects of acute resistance exercise in lean and obese skeletal muscle.Obesity (OB) impairs cell-to-cell communication signalling. Small extracellular vesicles (EVs), which include exosomes, are released by skeletal muscle and participate in cell-to-cell communication, including the regulation of angiogenesis. Resistance exercise (REx) increases muscle fibre size and capillarization. Although obesity increases muscle fibre size, there is an inadequate increase in capillarization such that capillary density is reduced. It was hypothesized that REx-induced angiogenic signalling and EV biogenesis would be lower with obesity. Sedentary lean (LN) and OB subjects (n = 8 per group) performed three sets of single-leg knee-extension REx at 80% of maximum. Muscle biopsies were obtained at rest, 15 min and 3 h postexercise and analysed for angiogenic and EV biogenesis mRNA and protein. In OB subjects, muscle fibre size was ∼20% greater and capillary density with type II fibres ∼25% lower compared with LN subjects (P 0.001). In response to REx, the increase in VEGF mRNA (pro-angiogenic) was similar (3-fold) between groups, while thrombospondin-1 (TSP-1) mRNA (anti-angiogenic) increased ∼2.5-fold in OB subjects only (P = 0.010). miR-130a (pro-angiogenic) was ∼1.4-fold (P = 0.011) and miR-503 (anti-angiogenic) ∼1.8-fold (P = 0.017) greater in OB compared with LN subjects at all time points. In both groups, acute REx decreased the EV surface protein Alix by ∼50%, consistent with the release of exosomes (P = 0.016). Acute REx appears to induce the release of skeletal muscle small EVs independent of body mass. However, with obesity there is predominantly impaired angiogenic signalling, consistent with inadequate angiogenesis in response to basal muscle hypertrophy.

OBJECTIVE: Burnout is prevalent among vascular surgery trainees. Here we aim to identify modifiable risk factors for burnout in vascular surgery training, to facilitate the development of programs to enhance and sustain trainee well-being. METHODS: The Association of Program Directors in Vascular Surgery issued the Annual Training survey in the fall of 2018 to all trainees. The survey contained items to assess frequency of burnout, as well as mentorship, training environment, and stress coping mechanisms using an abbreviated COPE (Coping Orientation to Problems Experienced) inventory. RESULTS: Of 628 surveys issued, the response rate was 30% (n = 188). Respondents indicated that the majority of programs offer mentorship opportunities (n = 150 [83%]) that are longitudinal throughout the duration of training (n = 140 [77%]). Fifty-eight percent (n = 109) indicated there was an appropriate balance between learning and productivity in their program, with more respondents leaning toward too much clinical productivity (n = 57) and fewer toward too much learning (n = 19). Forty-five percent of respondents indicated feeling burnout at least weekly (n = 81). The burnout group was less likely to report an appropriate balance between clinical productivity and learning (49.4% vs 67.7%; P < .001), as well as a lower frequency of mentorship opportunities (72.1% vs 92.7%; P < .001). Certain coping skills were used more frequently in the burnout group, including self-distraction, disengagement, humor, self-blame, and substance use. In multivariate analysis, frequent use of self-blame conferred a 9.847-fold increased risk (95% confidence interval, 2.114–45.871) of burnout (P = .003), while feeling appropriately challenged by the faculty was significantly protective (odds ratio for burnout, 0.158; 95% confidence interval, 0.031–0.820; P = .03). CONCLUSIONS: The protective effect against vascular surgery trainee burnout conferred by the availability of mentorship suggests that an expansion and emphasis on mentorship in training may help to mitigate trainee burnout. Mentorship may also be a suitable channel to assess for an appropriate level of challenge, as well as for an appropriate balance between clinical productivity and learning that, when present, are also protective against burnout. Furthermore, the correlation between the frequent use of certain coping skills and burnout highlight this as an area for intervention, potentially through a combination of mentor modeling and formal training on healthy stress-related coping strategies.

Background The literature directly comparing the utility of clinical examination (CE) to that of CT in detecting recurrence of squamous cell carcinoma (SCC) for primary site recurrences is lacking. Methods Patients who received both CT scans and CEs after primary treatment for SCC of the upper aerodigestive tract (oropharynx, hypopharynx, and larynx) were identified. Individual CT scans and CEs were evaluated for their ability to detect recurrence status. Results One hundred thirty-one patients underwent a total of 886 CEs and 346 CT scans during the follow-up period. The sensitivity for CE and CT was 84.0% and 66.7%, respectively; for specificity, 98.7% and 90.7%, respectively; for positive predictive value, 65.6% and 31.8%, respectively; and for negative predictive value the values were 99.5% and 97.7%, respectively. Conclusion Due to the low sensitivity and positive predictive value of CT scans compared to physical examination in evaluating primary site tumor recurrences, the utility of CT for surveillance may be limited. © 2010 Wiley Periodicals, Inc. Head Neck, 2011

Object The vertebral artery (VA) and its branches may be encountered during various neurosurgical procedures such as far lateral suboccipital approaches to the skull base and spinal operations. Therefore, a working knowledge of the distribution and significance of such VA branches may be advantageous to the surgeon. To date, quantitation of these branches is lacking in the literature. Methods The authors evaluated the branches of 20 VAs from 10 adult cadavers and assessed the distribution and surgical significance of the branches from the V2 and V3 segments. Results In terms of target tissues, the VA branches encountered at the C1–2 level were most likely to be muscular, branches at C2–3 osseous, and those at C3–6 radicular. No radicular or medullary branches were identified arising from any V3 segment of the VA or C1–2 level of the V2 segment. The greatest concentration of branches per level was found arising from the V2 segment at C2–3. Posterior branches of the VA tended to be radicular or muscular, whereas anterior branches tended to be radicular or osseous. Lateral branches were most commonly radicular and medial branches tended to be osseous or muscular in nature. The largest branches of the VA originated from its V3 segment or the C2–3 part of its V2 segment. Rarely, branches to the extracranial glossopharyngeal and spinal accessory nerves were identified originating from the V3 and V2 segments of the VA, respectively. Conclusions Although seemingly diverse in their distribution, the branches of the V2 and V3 segments of the VA may follow a certain consistent arrangement. The potential for injury to neural branches of the VA is minimal at its V3 segment and the C1–2 portion of its V2 segment. Such knowledge may be of use to the neurosurgeon who operates in the neck and at the craniocervical junction.