Mechanisms of Fatigability in People with Type 2 Diabetes and Prediabetes

Dynamic fatiguing exercise of limb muscles is the basis of exercise training and a cornerstone of management of type 2 diabetes mellitus (T2D) and prediabetes. Little is known however, about the fatigability of limb muscles (the acute exercise induced reduction in force or power) and the involved mechanisms in people with T2D and prediabetes. Current evidence suggests that people with T2D have reduced muscle strength and power, are more fatigable after static contractions, and have physical impairments affecting activities of daily living. However, impaired function in people with T2D compared with controls is larger for dynamic than static tasks. The purpose of this dissertation was to determine the magnitude and mechanisms of fatigability in people with T2D and prediabetes after a dynamic exercise task with the knee extensor muscles. Importantly, these studies matched people with T2D and prediabetes to controls based on age, sex, physical activity and body size. The first studies determined the magnitude of fatigability and the neural and muscular mechanisms in people with T2D and controls (Study 1) and in prediabetes (Study 2). People with T2D had approximately twice the decline in both power (fatigability) and electrically-evoked muscle contractile properties than controls after the six-minute dynamic task with the knee extensor muscles. People with prediabetes also had greater fatigability (~50%) and reductions in contractile properties than controls, but less than people with T2D. The reduction in voluntary activation (neural drive to the muscle) after fatiguing exercise was not different between people with T2D, prediabetes and controls. Thus, the greater fatigability in people with T2D was due to mechanisms within the skeletal muscle rather than neural drive. Study 3 determined whether skeletal muscle blood flow could explain the greater fatigability in people with T2D. People with T2D had greater fatigability and lower blood flow after exercise than controls, and there was an association between fatigability and the exercise-induced increase in muscle blood flow after exercise. Collectively, these data suggest that people with T2D and prediabetes have greater fatigability during dynamic exercise with knee extensor muscles due to mechanisms effecting muscle contractile properties, including impaired skeletal muscle blood flo

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

Fatigability of the Lumbopelvic Stabilizing Muscles in Women 8 and 26 Weeks Postpartum

Background: Pregnancy and childbirth are associated with lumbopelvic pain and instability. Fatigability of the lumbopelvic stabilizing muscles after childbirth is unknown, and no clinical tests exist to assess this important metric of muscle function. Objectives: To compare fatigability of the lumbopelvic stabilizing muscles in postpartum and nulligravid (control) women using the Active Straight Leg Raise (ASLR) Fatigue Task, and to determine whether fatigability is associated with interrecti distance (IRD), physical function, and pain/disability. Study design: A longitudinal case-control study. Methods: Twenty-nine nulligravid (25.4 +/- 9.1 years) and 31 postpartum women (31.4 +/- 5.2 years; vaginal delivery n = 18) were tested at 2 time points, 16 weeks apart (postpartum women tested at 8-10 and 24-26 weeks postpartum). Muscular function was assessed with manual muscle testing (MMT), the ASLR test, and a new ASLR Fatigue Task. Other measures included IRD, rectus abdominis thickness, physical activity, and 6-minute walk distance. Results: Postpartum women were 23% more fatigable (P = .028) and were weaker (MMT) (P \u3c .001) than controls up to 26 weeks postpartum. The ASLR Fatigue Task (time-to-failure) was associated with smaller IRD, greater rectus abdominis thickness, higher physical activity levels, greater MMT strength, and further distance walked in 6 minutes (P \u3c .05). Conclusion: Postpartum women (up to 6 months) had greater fatigability of the lumbopelvic stabilizing muscles and lower physical function than nulligravid women, suggesting core muscle function and fatigability should be assessed after pregnancy and childbirth. The ASLR Fatigue Task could be a clinically useful tool to determine fatigability of the lumbopelvic stabilizing muscles in women postpartum

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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