Physical Activity Modulates Corticospinal Excitability of the Lower Limb in Young and Old Adults

Aging is associated with reduced neuromuscular function, which may be due in part to altered corticospinal excitability. Regular physical activity (PA) may ameliorate these age-related declines, but the influence of PA on corticospinal excitability is unknown. The purpose of this study was to determine the influence of age, sex, and PA on corticospinal excitability by comparing the stimulus-response curves of motor evoked potentials (MEP) in 28 young (22.4 ± 2.2 yr; 14 women and 14 men) and 50 old adults (70.2 ± 6.1 yr; 22 women and 28 men) who varied in activity levels. Transcranial magnetic stimulation was used to elicit MEPs in the active vastus lateralis muscle (10% maximal voluntary contraction) with 5% increments in stimulator intensity until the maximum MEP amplitude. Stimulus-response curves of MEP amplitudes were fit with a four-parameter sigmoidal curve and the maximal slope calculated (slopemax). Habitual PA was assessed with tri-axial accelerometry and participants categorized into either those meeting the recommended PA guidelines for optimal health benefits (\u3e10,000 steps/day, high-PA; n = 21) or those not meeting the guidelines (n = 41). The MEP amplitudes and slopemax were greater in the low-PA compared with the high-PA group (P \u3c 0.05). Neither age nor sex influenced the stimulus-response curve parameters (P \u3e 0.05), suggesting that habitual PA influenced the excitability of the corticospinal tract projecting to the lower limb similarly in both young and old adults. These findings provide evidence that achieving the recommended PA guidelines for optimal health may mediate its effects on the nervous system by decreasing corticospinal excitability

Physical Activity Modulates Corticospinal Excitability of the Lower Limb in Young and Old Adults

Aging is associated with reduced neuromuscular function, which may be due in part to altered corticospinal excitability. Regular physical activity (PA) may ameliorate these age-related declines, but the influence of PA on corticospinal excitability is unknown. The purpose of this study was to determine the influence of age, sex, and PA on corticospinal excitability by comparing the stimulus-response curves of motor evoked potentials (MEP) in 28 young (22.4 ± 2.2 yr; 14 women and 14 men) and 50 old adults (70.2 ± 6.1 yr; 22 women and 28 men) who varied in activity levels. Transcranial magnetic stimulation was used to elicit MEPs in the active vastus lateralis muscle (10% maximal voluntary contraction) with 5% increments in stimulator intensity until the maximum MEP amplitude. Stimulus-response curves of MEP amplitudes were fit with a four-parameter sigmoidal curve and the maximal slope calculated (slopemax). Habitual PA was assessed with tri-axial accelerometry and participants categorized into either those meeting the recommended PA guidelines for optimal health benefits (\u3e10,000 steps/day, high-PA; n = 21) or those not meeting the guidelines (n = 41). The MEP amplitudes and slopemax were greater in the low-PA compared with the high-PA group (P \u3c 0.05). Neither age nor sex influenced the stimulus-response curve parameters (P \u3e 0.05), suggesting that habitual PA influenced the excitability of the corticospinal tract projecting to the lower limb similarly in both young and old adults. These findings provide evidence that achieving the recommended PA guidelines for optimal health may mediate its effects on the nervous system by decreasing corticospinal excitability

Age-related Deficits in Voluntary Activation: A Systematic Review and Meta-analysis

Whether there are age-related differences in neural drive during maximal effort contractions is not clear. This review determined the effect of age on voluntary activation during maximal voluntary isometric contractions. The literature was systematically reviewed for studies reporting voluntary activation quantified with the interpolated twitch technique (ITT) or central activation ratio (CAR) during isometric contractions in young (18–35 yr) and old adults (\u3e60 yr; mean, ≥65 yr). Of the 2697 articles identified, 54 were eligible for inclusion in the meta-analysis. Voluntary activation was assessed with electrical stimulation and transcranial magnetic stimulation on five different muscle groups. Random-effects meta-analysis revealed lower activation in old compared with young adults (d = −0.45; 95% confidence interval, −0.62 to −0.29; P \u3c 0.001), with moderate heterogeneity (52.4%). To uncover the sources of heterogeneity, subgroup analyses were conducted for muscle group, calculation method (ITT or CAR), and stimulation type (electrical stimulation or transcranial magnetic stimulation) and number (single, paired, or train stimulations). The age-related reduction in voluntary activation occurred for all muscle groups investigated except the ankle dorsiflexors. Both ITT and CAR demonstrated an age-related reduction in voluntary activation of the elbow flexors, knee extensors, and plantar flexors. ITT performed with paired and train stimulations showed lower activation for old than young adults, with no age difference for the single electrical stimulation. Together, the meta-analysis revealed that healthy older adults have a reduced capacity to activate some upper and lower limb muscles during maximal voluntary isometric contractions; however, the effect was modest and best assessed with at least paired stimulations to detect the difference

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

The effects of computerised cognitive training on post-CABG delirium and cognitive change: A prospective randomised controlled trial

Background: Cognitive impairments, including delirium, are common after coronary artery bypass grafting (CABG). Improving cognition pre- and post-operatively using computerised cognitive training (CCT) may be an effective approach to improve cognitive outcomes in CABG patients. Objectives: Investigate the effect of remotely supervised CCT on cognitive outcomes, including delirium, in older adults undergoing CABG surgery. Methods: Thirty-six participants, were analysed in a single-blinded randomised controlled trial (CCT Intervention: n = 18, Control: n = 18). CCT was completed by the intervention group pre-operatively (every other day, 45–60-minute sessions until surgery) and post-operatively, beginning 1-month post-CABG (3 x 45–60-minute sessions/week for 12-weeks), while the control group maintained usual care plus weekly phone calls. Cognitive assessments were conducted pre- and post-operatively at multiple follow-ups (discharge, 4-months and 6-months). Post-operative delirium incidence was assessed daily until discharge. Cognitive change data were calculated at each follow-up for each cognitive test (Addenbrooke’s Cognitive Examination III and CANTAB; z-scored). Results: Adherence to the CCT intervention (completion of three pre-operative or 66% of post-operative sessions) was achieved in 68% of pre-CABG and 59% of post-CABG participants. There were no statistically significant effects of CCT on any cognitive outcome, including delirium incidence. Conclusion: Adherence to the CCT program was comparatively higher than previous feasibility studies, possibly due to the level of supervision and support provided (blend of face-to-face and home-based training, with support phone calls). Implementing CCT interventions both pre- and post-operatively is feasible in those undergoing CABG. No statistically significant benefits from the CCT interventions were identified for delirium or cognitive function post-CABG, likely due to the sample size available (study recruitment greatly impacted by COVID-19). It also may be the case that multimodal intervention would be more effective

The association between reallocations of time and health using compositional data analysis: a systematic scoping review with an interactive data exploration interface

Background: How time is allocated influences health. However, any increase in time allocated to one behaviour must be offset by a decrease in others. Recently, studies have used compositional data analysis (CoDA) to estimate the associations with health when reallocating time between different behaviours. The aim of this scoping review was to provide an overview of studies that have used CoDA to model how reallocating time between different time-use components is associated with health. Methods: A systematic search of four electronic databases (MEDLINE, Embase, Scopus, SPORTDiscus) was conducted in October 2022. Studies were eligible if they used CoDA to examine the associations of time reallocations and health. Reallocations were considered between movement behaviours (sedentary behaviour (SB), light physical activity (LPA), moderate-to-vigorous physical activity (MVPA)) or various activities of daily living (screen time, work, household chores etc.). The review considered all populations, including clinical populations, as well as all health-related outcomes. Results: One hundred and three studies were included. Adiposity was the most commonly studied health outcome (n = 41). Most studies (n = 75) reported reallocations amongst daily sleep, SB, LPA and MVPA. While other studies reported reallocations amongst sub-compositions of these (work MVPA vs. leisure MVPA), activity types determined by recall (screen time, household chores, passive transport etc.) or bouted behaviours (short vs. long bouts of SB). In general, when considering cross-sectional results, reallocating time to MVPA from any behaviour(s) was favourably associated with health and reallocating time away from MVPA to any behaviour(s) was unfavourably associated with health. Some beneficial associations were seen when reallocating time from SB to both LPA and sleep; however, the strength of the association was much lower than for any reallocations involving MVPA. However, there were many null findings. Notably, most of the longitudinal studies found no associations between reallocations of time and health. Some evidence also suggested the context of behaviours was important, with reallocations of leisure time toward MVPA having a stronger favourable association for health than reallocating work time towards MVPA. Conclusions: Evidence suggests that reallocating time towards MVPA from any behaviour(s) has the strongest favourable association with health, and reallocating time away from MVPA toward any behaviour(s) has the strongest unfavourable association with health. Future studies should use longitudinal and experimental study designs, and for a wider range of outcomes

Clinical benefit of glasdegib plus low-dose cytarabine in patients with de novo and secondary acute myeloid leukemia: long-term analysis of a phase II randomized trial

This analysis from the phase II BRIGHT AML 1003 trial reports the long-term efficacy and safety of glasdegib + low-dose cytarabine (LDAC) in patients with acute myeloid leukemia ineligible for intensive chemotherapy. The multicenter, open-label study randomized (2:1) patients to receive glasdegib + LDAC (de novo, n = 38; secondary acute myeloid leukemia, n = 40) or LDAC alone (de novo, n = 18; secondary acute myeloid leukemia, n = 20). At the time of analysis, 90% of patients had died, with the longest follow-up since randomization 36 months. The combination of glasdegib and LDAC conferred superior overall survival (OS) versus LDAC alone; hazard ratio (HR) 0.495; (95% confidence interval [CI] 0.325–0.752); p = 0.0004; median OS was 8.3 versus 4.3 months. Improvement in OS was consistent across cytogenetic risk groups. In a post-hoc subgroup analysis, a survival trend with glasdegib + LDAC was observed in patients with de novo acute myeloid leukemia (HR 0.720; 95% CI 0.395–1.312; p = 0.14; median OS 6.6 vs 4.3 months) and secondary acute myeloid leukemia (HR 0.287; 95% CI 0.151–0.548; p < 0.0001; median OS 9.1 vs 4.1 months). The incidence of adverse events in the glasdegib + LDAC arm decreased after 90 days’ therapy: 83.7% versus 98.7% during the first 90 days. Glasdegib + LDAC versus LDAC alone continued to demonstrate superior OS in patients with acute myeloid leukemia; the clinical benefit with glasdegib + LDAC was particularly prominent in patients with secondary acute myeloid leukemia. ClinicalTrials.gov identifier: NCT01546038.Open Access funding enabled and organized by Projekt DEAL. This study was funded by Pfizer.Peer reviewe

The aggregation of an alkyl-C₆₀ derivative as a function of concentration, temperature and solvent type

Contrast-variation SANS, SAXS, NMR and ITC measurements show that molecule1associates into micelles with tunable size based on the solution parameters.</p

Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials