Anabolic resistance of muscle protein turnover comes in various shapes and sizes

Anabolic resistance is defined by a blunted stimulation of muscle protein synthesis rates (MPS) to common anabolic stimuli in skeletal muscle tissue such as dietary protein and exercise. Generally, MPS is the target of most exercise and feeding interventions as muscle protein breakdown rates seem to be less responsive to these stimuli. Ultimately, the blunted responsiveness of MPS to dietary protein and exercise underpins the loss of the amount and quality of skeletal muscle mass leading to decrements in physical performance in these populations. The increase of both habitual physical activity (including structured exercise that targets general fitness characteristics) and protein dense food ingestion are frontline strategies utilized to support muscle mass, performance, and health. In this paper, we discuss anabolic resistance as a common denominator underpinning muscle mass loss with aging, obesity, and other disease states. Namely, we discuss the fact that anabolic resistance exists as a dimmer switch, capable of varying from higher to lower levels of resistance, to the main anabolic stimuli of feeding and exercise depending on the population. Moreover, we review the evidence on whether increased physical activity and targeted exercise can be leveraged to restore the sensitivity of skeletal muscle tissue to dietary amino acids regardless of the population

Plastic formulation is an emerging control of its photochemical fate in the ocean

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Walsh, A. N., Reddy, C. M., Niles, S. F., McKenna, A. M., Hansel, C. M., & Ward, C. P. Plastic formulation is an emerging control of its photochemical fate in the ocean. Environmental Science & Technology, 55(18), (2021): 12383–12392, https://doi.org/10.1021/acs.est.1c02272.Sunlight exposure is a control of long-term plastic fate in the environment that converts plastic into oxygenated products spanning the polymer, dissolved, and gas phases. However, our understanding of how plastic formulation influences the amount and composition of these photoproducts remains incomplete. Here, we characterized the initial formulations and resulting dissolved photoproducts of four single-use consumer polyethylene (PE) bags from major retailers and one pure PE film. Consumer PE bags contained 15–36% inorganic additives, primarily calcium carbonate (13–34%) and titanium dioxide (TiO2; 1–2%). Sunlight exposure consistently increased production of dissolved organic carbon (DOC) relative to leaching in the dark (3- to 80-fold). All consumer PE bags produced more DOC during sunlight exposure than the pure PE (1.2- to 2.0-fold). The DOC leached after sunlight exposure increasingly reflected the 13C and 14C isotopic composition of the plastic. Ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry revealed that sunlight exposure substantially increased the number of DOC formulas detected (1.1- to 50-fold). TiO2-containing bags photochemically degraded into the most compositionally similar DOC, with 68–94% of photoproduced formulas in common with at least one other TiO2-containing bag. Conversely, only 28% of photoproduced formulas from the pure PE were detected in photoproduced DOC from the consumer PE. Overall, these findings suggest that plastic formulation, especially TiO2, plays a determining role in the amount and composition of DOC generated by sunlight. Consequently, studies on pure, unweathered polymers may not accurately represent the fates and impacts of the plastics entering the ocean.Funding was provided by the Seaver Institute, the Gerstner Family Foundation, Woods Hole Oceanographic Institution, and the National Science Foundation Graduate Research Fellowship Program (A.N.W.). The Ion Cyclotron Resonance user facility at the National High Magnetic Field Laboratory is supported by the National Science Foundation Division of Chemistry and Division of Materials Research through DMR-1644779 and the State of Florida

Evidencing the impact of teaching-related CPD: beyond the ‘Happy Sheets’

peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope. aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=rija2

Peri-Pubertal Emergence of UNC-5 Homologue Expression by Dopamine Neurons in Rodents

Puberty is a critical period in mesocorticolimbic dopamine (DA) system development, particularly for the medial prefrontal cortex (mPFC) projection which achieves maturity in early adulthood. The guidance cue netrin-1 organizes neuronal networks by attracting or repelling cellular processes through DCC (deleted in colorectal cancer) and UNC-5 homologue (UNC5H) receptors, respectively. We have shown that variations in netrin-1 receptor levels lead to selective reorganization of mPFC DA circuitry, and changes in DA-related behaviors, in transgenic mice and in rats. Significantly, these effects are only observed after puberty, suggesting that netrin-1 mediated effects on DA systems vary across development. Here we report on the normal expression of DCC and UNC5H in the ventral tegmental area (VTA) by DA neurons from embryonic life to adulthood, in both mice and rats. We show a dramatic and enduring pubertal change in the ratio of DCC:UNC5H receptors, reflecting a shift toward predominant UNC5H function. This shift in DCC:UNC5H ratio coincides with the pubertal emergence of UNC5H expression by VTA DA neurons. Although the distribution of DCC and UNC5H by VTA DA neurons changes during puberty, the pattern of netrin-1 immunoreactivity in these cells does not. Together, our findings suggest that DCC:UNC5H ratios in DA neurons at critical periods may have important consequences for the organization and function of mesocorticolimbic DA systems

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Exercising to offset muscle mass loss in hemodialysis patients: The disconnect between intention and intervention

Skeletal muscle loss is the most important hallmark of protein energy wasting syndrome as it contributes to declines in physical independence, poor quality of life, and higher mortality risk in individuals with ESRD on maintenance hemodialysis (HD). As such, exercise and nutritional interventions have been investigated with the goal to preserve skeletal muscle mass and overall quality of life. Unfortunately, current efforts are unable to confirm the capacity of exercise to mitigate ESRD‐associated muscle wasting. However, the inconclusive data are often accompanied by suboptimal exercise prescriptions. Exercise sessions are often implemented in‐clinic during the catabolic and proinflammatory period of dialysis treatment and without concurrent nutritional support. Additionally, indirect considerations like exercise intolerance and exercise program compliance/adherence also inhibit exercise training potential. These shortcomings all stem from the current lack of understanding in skeletal muscle mass regulation within the context of ESRD and intermittent HD. As such, this review summarizes the current understanding of exercise regulation on skeletal muscle mass and ESRD‐related obstacles of anabolism to contextualize the ineffectiveness of current exercise interventions for HD patients

Potato Ingestion as an Effective Race Fuel Alternative to Improve Cycling Performance in Trained Cyclists

Carbohydrate (CHO) ingestion is an established strategy to improve endurance performance. Race fuels should not only sustain performance, but also be readily digested and absorbed and replenish electrolytes. Potatoes are a cost-effective option that fulfills these criteria; however, their impact on endurance performance remains unexamined. PURPOSE: Compare the effects of potato purée (POT) ingestion during endurance cycling on subsequent performance versus commercial CHO gel (GEL) or a control (water, CTL). METHODS: Twelve trained cyclists (31±9y; 71±8kg; VO2max: 61±9mL/kg/min) consumed a standardized breakfast then performed a 2h cycling challenge (60-85%VO2max) followed by a time trial (6kJ/kg body mass) while consuming POT, GEL, or CTL in a randomized-crossover design. POT, GEL and CTL were administered with U-[13C6]glucose for an indirect estimate of gastric emptying rate. Repeated blood samples were collected. RESULTS: Time trial performance significantly improved (P=0.03) with POT (33.0±4.5min) and GEL (33.0±4.2min) versus CTL condition (39.5±7.9min); while POT and GEL conditions (P=1.00) had no difference. Post-challenge, blood glucose concentrations were lower (P0.05). CONCLUSION: Potatoes served as a viable alternative to commercial gels by sustaining performance and blood glucose concentrations during endurance cycling events in trained cyclists

Use of a Simulation-based Advanced Resuscitation Training Curriculum: Impact on Cardiopulmonary Resuscitation Quality and Patient Outcomes

Background: Despite a continued focus on improved cardiopulmonary resuscitation quality, survival remains low from in-hospital cardiac arrest. Advanced Resuscitation Training has been shown to improve survival to hospital discharge and survival with good neurological outcome following in-hospital cardiac arrest at its home institution. We sought to determine if Advanced Resuscitation Training implementation would improve patient outcomes and cardiopulmonary resuscitation quality at our institution. Methods: This was a prospective, before–after study of adult in-hospital cardiac arrest victims who had cardiopulmonary resuscitation performed. During phase 1, standard institution cardiopulmonary resuscitation training was provided. During phase 2, providers received the same quantity of training, but with emphasis on Advanced Resuscitation Training principles. Primary outcomes were return of spontaneous circulation, survival to hospital discharge, and neurologically favorable survival. Secondary outcomes were cardiopulmonary resuscitation quality parameters. Results: A total of 156 adult in-hospital cardiac arrests occurred during the study period. Rates of return of spontaneous circulation improved from 58.1 to 86.3% with an adjusted odds ratios of 5.31 (95% CI: 2.23–14.35, P \u3c 0.001). Survival to discharge increased from 26.7 to 41.2%, adjusted odds ratios 2.17 (95% CI: 1.02–4.67, P \u3c 0.05). Survival with a good neurological outcome increased from 24.8 to 35.3%, but was not statistically significant. Target chest compression rate increased from 30.4% of patients in P1 to 65.6% in P2, adjusted odds ratios 4.27 (95% CI: 1.72–11.12, P = 0.002), and target depth increased from 23.2% in P1 to 46.9% in P2, adjusted odds ratios 2.92 (95% CI: 1.16–7.54, P = 0.024). Conclusions: After Advanced Resuscitation Training implementation, there were significant improvements in cardiopulmonary resuscitation quality and rates of return of spontaneous circulation and survival to discharge