Voluntary Activation and Variability During Maximal Dynamic Contractions with Aging

Whether reduced supraspinal activation contributes to age-related reductions in maximal torque during dynamic contractions is not known. The purpose was to determine whether there are age differences in voluntary activation and its variability when assessed with stimulation at the motor cortex and the muscle during maximal isometric, concentric, and eccentric contractions. Thirty young (23.6 ± 4.1 years) and 31 old (69.0 ± 5.2 years) adults performed maximal isometric, shortening (concentric) and lengthening (eccentric) contractions with the elbow flexor muscles. Maximal isometric contractions were performed at 90° elbow flexion and dynamic contractions at a velocity of 60°/s. Voluntary activation was assessed by superimposing an evoked contraction with transcranial magnetic stimulation (TMS) or with electrical stimulation over the muscle during maximal voluntary contractions (MVCs). Old adults had lower MVC torque during isometric (− 17.9%), concentric (− 19.7%), and eccentric (− 9.9%) contractions than young adults, with less of an age difference for eccentric contractions. Voluntary activation was similar between the three contraction types when assessed with TMS and electrical stimulation, with no age group differences. Old adults, however, were more variable in voluntary activation than young (standard deviation 0.99 ± 0.47% vs. 0.73 ± 0.43%, respectively) to both the motor cortex and muscle, and had greater coactivation of the antagonist muscles during dynamic contractions. Thus, the average voluntary activation to the motor cortex and muscle did not differ with aging; however, supraspinal activation was more variable during maximal dynamic and isometric contractions in the old adults. Lower predictability of voluntary activation may indicate subclinical changes in the central nervous system with advanced aging

Access to and safety of COVID-19 convalescent plasma in the United States Expanded Access Program: A national registry study

BACKGROUND: The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma. METHODS AND FINDINGS: Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician-principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had-or were at risk of progression to-severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (\u3c1%), and the overall crude 30-day mortality rate was 25.2% (95% CI, 25.0% to 25.5%). This registry study was limited by the observational and pragmatic study design that did not include a control or comparator group; thus, the data should not be used to infer definitive treatment effects. CONCLUSIONS: These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT#: NCT04338360

Use of convalescent plasma in COVID-19 patients with immunosuppression

In the absence of effective countermeasures, human convalescent plasma has been widely used to treat severe acute respiratory syndrome coronavirus 2, the causative agent of novel coronavirus disease 19 (COVID-19), including among patients with innate or acquired immunosuppression. However, the association between COVID-19-associated mortality in patients with immunosuppression and therapeutic use of convalescent plasma is unknown. We review 75 reports, including one large matched-control registry study of 143 COVID-19 patients with hematological malignancies, and 51 case reports and 23 case series representing 238 COVID-19 patients with immunosuppression. We review clinical features and treatment protocols of COVID-19 patients with immunosuppression after treatment with human convalescent plasma. We also discuss the time course and clinical features of recovery. The available data from case reports and case series provide evidence suggesting a mortality benefit and rapid clinical improvement in patients with several forms of immunosuppression following COVID-19 convalescent plasma transfusion. The utility of convalescent plasma or other forms of antibody therapy in immune-deficient and immune-suppressed patients with COVID-19 warrants further investigation

Differential Effects of Aging and Physical Activity on Corticospinal Excitability of Upper and Lower Limb Muscles

Corticospinal tract excitability can be altered by age, physical activity (PA), and possibly sex, but whether these effects differ between upper and lower limb muscles is unknown. We determined the influence of age, PA, and sex on corticospinal excitability of an upper limb and a lower limb muscle during submaximal contractions by comparing stimulus-response curves of motor evoked potentials (MEPs). Transcranial magnetic stimulation (TMS) was used to evoke stimulus-response curves in active muscles by incrementally increasing the stimulator intensity from below the active motor threshold (AMT) until a plateau in MEP amplitudes was achieved. Stimulus-response curves were analyzed from the first dorsal interosseous (FDI) of 30 young (23.9 ± 3.8 yr) and 33 older (72.6 ± 5.6 yr) men and women and the vastus lateralis (VL) of 13 young (23.2 ± 2.2 yr) and 25 older (72.7 ± 5.5 yr) men and women. Corticospinal excitability was determined by fitting the curves with a four-parameter sigmoidal curve and calculating the maximal slope (slopemax). PA was assessed with triaxial accelerometry, and participants were dichotomized into high-PA (\u3e10,000 steps/day, n = 15) or low-PA (n = 43) groups. Young adults had larger FDI MEP amplitudes (% maximum amplitude of compound muscle action potential) at higher TMS intensities (120–150% AMT) and greater slopemax than older adults (P \u3c 0.05), with no differences between high- and low-PA groups (P \u3e 0.05). VL MEP amplitudes and slopemax, however, were lower in the high-PA than low-PA participants, with no age or sex differences. These data suggest that aging and PA, but not sex, differentially influence the excitability of the corticospinal tracts projecting to muscles of the upper compared with the lower limb

Commentaries on viewpoint : physiology and fast marathons

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Are masters athletic performances predictive of human aging in men and women?

Human aging particularly after ∼70 years, is associated with declines in physical function and athletic performance, that are accelerated in part by age-associated declines in physical activity and exercise training. Because elite athletes maintain high levels of physical activity across the lifespan, older athletes (Masters) may present as a proxy for healthy human aging. Although longitudinal studies are most informative about human aging, there are substantial practical challenges to conducting longitudinally designed research. Masters athletic records and comparisons of performance across age groups can serve as a practical and unique probe to predict the trajectory of human function throughout the lifespan. While useful, the cross-sectional comparison of elite athletic performance across different age groups, however, has inherent limitations in predicting healthy human aging, particularly among women. This review presents evidence that (1) there is a progressive age-related decline in world class performances in freestyle swim swimming, marathon, and triathlon, that accelerates into very old age (∼70 years), and (2) lower participation rates of women relative to men results in an overestimation of the age-related decline in athletic performance particularly in very old women. Thus, while useful, there are some limitations to predicting biological aging among women using current Masters Athletic performances

Sex differences in youth elite swimming.

BackgroundThe timing and magnitude of sex differences in athletic performance during early human development, prior to adulthood, is unknown.ObjectiveTo compare swimming velocity of boys and girls for all Olympic-length freestyle swimming events to determine the age of divergence in swimming performance.MethodsWe collected the all-time top 100 U.S. freestyle swimming performance times of boys and girls age 5 to 18 years for the 50m to 1500m events.ResultsSwimming performance improved with increasing age for boys and girls (pConclusionThe top 5 girls demonstrated faster swimming velocities and the 10th-50th place girls demonstrated similar swimming velocities than boys (until ~10 years). After age 10, however, boys demonstrated increasingly faster swimming velocities than girls until 17 years. Collectively, these data suggest girls are faster, or at least not slower, than boys prior to the performance-enhancing effects of puberty