The present study investigated the effects of exercising with self-selected music on exercise tolerance and related physiological responses during endurance cycling. Recreationally active adults (N = 29) completed two time-to-exhaustion (TTE) trials at ∼80% of peak power output under counterbalanced conditions: music (self-selected, 120-140 bpm) and no-music. Participants cycled longer with music (M = 35.61, SD = 14.01 min) than without (M = 29.80, SD = 11.47 min), t (28) = 3.62, p = .001, dz = 0.67. Heart-rate (HR) analyses (N = 27) showed greater cumulative cardiovascular load under music (AUC +15.4% vs no-music; t (26) = 2.40, p = .024), and a small isotime HR increase (+2.9 bpm, ∼+1.9%; t (26) = 2.75, p = .011). Music also extended the time participants tolerated suprathreshold effort, both in absolute (p < .001) and proportional (p = .005) terms. Total energy expenditure was higher with music (+69 kJ; +17%; t (28) = 3.34, p = .002), whereas energy-expenditure rate did not differ (+0.11 kJ min-1; p = .652); post-exercise lactate was unaffected after controlling for TTE (cond. +0.32-0.39 mmol·L-1; p ≥ .265). Aerobic fitness (VO2peak) did not moderate the ergogenic effect (r = -0.28, p = .135). Despite longer performance and higher cumulative exposure, terminal responses (end %HRmax, %VO2peak, RPE, lactate) were similar (all p ≥ .14). Qualitative data contextualised the participant experience. Results suggest that self-selected music may facilitate tolerance of sustained effort consistent with altered tolerance of effort rather than improved metabolic efficiency.

Diabetes is a rapidly growing non-communicable disease globally, with 360 million out of 537 million affected adults residing in urban centres in 2021. In Pakistan, the situation is alarming, with diabetes prevalence alone exceeding 28.3

Abstract This study investigated sex differences in neuromuscular responses during dynamic balance perturbations and isometric maximal voluntary contractions (IMVCs) by examining if menstrual cycle (MC) phase and the fluctuations in endogenous hormones influence the observation of sex differences. Twenty‐seven young adults (17 males: 28.5 ± 6.4 years; 10 females: 31.2 ± 6.5 years) were measured twice: females were measured at the early‐follicular (EF) phase, that is 2–4 days after onset of bleeding, and at the mid‐luteal phase (LUT), coinciding with peak levels of progesterone. Males were measured twice with 7–14 days between measurements. During dynamic balance perturbations, H‐reflex and V‐wave (neural drive) responses were recorded from the posterior perturbations at four latencies (40 ms, 70 ms, 100 ms, and 130 ms) coinciding with short‐ (SLR), medium‐ (MLR), and long‐ (LLR) latency responses and voluntary activation. Further, IMVC and its associated neural drive were assessed. Sex differences in either the H‐reflex (P = 0.217) or the V‐wave (P = 0.475) were not observed during balance perturbation tasks when females at EF were compared to males. However, when the measurements were conducted at LUT, a significant sex difference was revealed in both H‐reflex (P = 0.029) and V‐wave (P = 0.049) responses. Similarly, in neural drive during IMVC, no sex differences were observed at EF (P = 0.440), but a significant sex difference at LUT was observed (P = 0.024). Our results suggest that hormonal fluctuation in two distinct MC phases lead to females having lower neural responses during dynamic balance and voluntary force generation tasks at LUT compared to males.

Health technology assessment (HTA) processes provide evidence to inform the supply of healthcare, often comparing results from economic evaluation to a policy threshold to judge cost-effectiveness. However, recommended policy thresholds may not always align with empirical estimates of the opportunity costs of health care expenditure, captured by marginal productivity of healthcare expenditure (‘k’). Such estimates are needed to inform the net health impact of funding decisions. We map policy thresholds in HTA guidelines against published estimates of k. We extract information from HTA guidelines identified in a previous literature review, including recommended perspective, relevant costs and outcomes, and justification for the threshold. Studies estimating k were obtained from a separate review. Of the 47 included HTA guidelines, 20 state an explicit policy threshold and 12 justify their choice. Estimates of k were available for 13 countries. Among the eight countries with explicit policy thresholds and k estimates, three matched. The recommended perspective influences whether k alone is sufficient or appropriate to inform cost-effectiveness judgements. It is important that guideline setters are aware of empirical estimates of k; and that economic evaluations consider k to reflect health opportunity costs even where the policy threshold is justified on other grounds.

Objectives: Many health systems aim to reduce health inequalities. Reimbursement mechanisms for healthcare providers, including pay-for-performance, are common policy levers to align provider behavior with health systems objectives. We develop a methodology to incorporate equity concerns into value-based pricing in the English National Health Service. We focus on socioeconomic inequalities in health measured by deprivation quintiles. We show how changes in the design of a national pay-for-performance scheme in primary care, the Quality Outcome Framework, can be evaluated in terms of their effects on the level and distribution of health across socioeconomic status. Methods: After developing our theoretical framework, which is based on Distributional Cost-Effectiveness Analysis and contract theory, we calibrate a model of physician behavior using information on costs and health benefits of different incentivized activities, achievement rates, and supply responsiveness to prices. We evaluate the effect of hypothetical 20% increases in price of 1 incentivized activity, which is financed by a reduction in another price to retain budget neutrality. Trade-offs between efficiency and socioeconomic inequalities in health are evaluated using the Equally Distributed Equivalent level of health. Results: We illustrate our methodology using 3 scenarios: changes in prices for 2 incentivized activities for the same health condition (diabetes), different health conditions (diabetes and chronic obstructive pulmonary disease), and across socioeconomic groups within the same activity (flu vaccination for diabetes patients). Conclusions: Our analysis illustrates how inequality aversion can be incorporated into value-based pricing when assessing the effect of financial incentives on the health distribution across socioeconomic groups.

ABSTRACT:Rostami, M, Lee, A, Frazer, AK, Akalu, Y, Tallent, J, Walker, S, and Kidgell DJ. Strength training preferentially enhances corticospinal output compared to high-intensity interval training. J Strength Cond Res 40(4): 386-399, 2026-Corticospinal responses to motor training are influenced by the specific task, muscle group involved, and contraction type. Yet, the distinct effects of high-intensity interval training (HIIT) and strength exercise ( SE ) on corticospinal excitability and inhibition remain unclear. Although most studies focus on upper-limb muscles not directly engaged in HIIT, this study investigated corticospinal, intracortical, and spinal responses in lower-limb muscles actively involved in both exercises. Eighteen healthy untrained subjects completed a 20-minute high-intensity interval cycling task (HIIT), a single bout of high-intensity SE , and a no-exercise control session on separate days. Corticospinal, intracortical, and spinal responses were assessed using transcranial magnetic stimulation (TMS) and peripheral nerve stimulation at baseline and 5 minutes postexercise. Compared with control, both HIIT and SE significantly increased motor-evoked potential (MEP) amplitude at 130% active motor threshold (AMT) (HIIT: p = 0.006; SE : p < 0.001), with SE inducing substantially greater increases than HIIT ( p < 0.001). At 150% AMT, only SE significantly increased MEP amplitude compared with baseline, control, and HIIT ( p < 0.001). Silent period duration was significantly reduced following SE at 130% AMT ( p = 0.004) and following both HIIT ( p = 0.03) and SE ( p = 0.04) at 150% AMT. Only SE led to significant reduction in short-interval intracortical inhibition ( p = 0.02). Spinal excitability remained unchanged. These findings highlight task-dependent corticospinal plasticity in lower-limb muscles and suggest that SE may be particularly effective for enhancing acute corticospinal excitability, with potential implications for neurorehabilitation programs targeting conditions associated with reduced corticospinal excitability.

Examining ipsilateral motor pathways, purportedly reflecting cortico-reticulospinal excitability, has received growing attention in rehabilitation and exercise science. However, the reliability of measures used to assess its excitability, such as ipsilateral motor-evoked potential (iMEP), remains largely unverified. Fifty-three participants (26 males and 27 females) completed two laboratory visits 1 wk apart. Dominant arm contralateral MEP (cMEP) and nondominant arm iMEP, along with maximal compound muscle action potential (M-max), from both m.biceps brachii were recorded. After determination of preacher curl one-repetition maximum (1-RM), participants performed four sets of five preacher curl repetitions at 30% of 1-RM, with 30 s rest between sets. Transcranial magnetic stimulation was delivered at 100% of maximum stimulator output during the concentric phase of the contraction (110° of flexion). Intraclass correlation coefficients (ICCs) for all variables indicated good-to-excellent intrasession (ICC ≥ 0.88) and intersession reliability (ICC ≥ 0.80). Notably, the ICCs for iMEP and cMEP amplitudes demonstrated excellent reliability for both intrasession (ICC ≥ 0.98) and intersession (ICC ≥ 0.91) measurements. iMEP presence was reliable (ICC = 0.87) and had similar variability as iMEP amplitude. However, ICC for iMEP/cMEP ratio (ICAR) was 0.83, and there was substantial intersession variability (coefficient of variation = 56.8%; relative standard error of measurement = 31.7%). Sex did not influence the reliability of the measures. iMEP and cMEP measured during preacher curl exhibited excellent intrasession and good-to-excellent intersession reliability in both sexes. Thus, this test is a useful tool to evaluate cortico-reticulospinal and corticospinal excitability in humans, although caution is advised if using ICAR.NEW & NOTEWORTHY The cortico-reticulospinal tract is now thought to be an important regulator of voluntary force, but there is a shortage of accepted measures assessing its excitability. Here, we used transcranial magnetic stimulation to elicit ipsilateral motor-evoked potentials (iMEPs) in a large group of healthy males and females. We demonstrated good-to-excellent reproducibility across all iMEP characteristics (including latency, amplitude, and presence) in both sexes. iMEPs are, thus, a useful tool to assess cortico-reticulospinal excitability.

INTRODUCTION:Resistance exercise is the primary strategy to counteract age-related declines in muscle function. Training loads are typically prescribed relative to an individual's one-repetition maximum (1-RM), but direct 1-RM testing is time-consuming and may increase injury risk in older adults. Because movement velocity can predict relative load, this cross-sectional study examined the accuracy of 1-RM estimation from individual load-velocity (L-v) profiles. METHODS:Ninety-six participants (60 males, 36 females; 69 ± 5.8 years) performed unilateral explosive repetitions on a pneumatic leg press at five submaximal loads to generate individualized L-v equations, followed by single repetitions to determine 1-RM. The group's sex-specific average measured velocity at 1-RM (V1RM; males: 0.17 ± 0.08 m·s-1, females: 0.18 ± 0.09 m·s-1) was defined. A corrected V1RM, which accounted for non-linearity of the L-v relationship near maximal load, was also calculated (males: 0.31 ± 0.15 m·s-1, females: 0.33 ± 0.12 m·s-1). To estimate 1-RM, measured V1RM and corrected V1RM values were input into the individual L-v equations. RESULTS:Estimates based on measured V1RM overestimated 1-RM (mean difference = -7.7 ± 7.4 kg; d = 1.05) and did not achieve statistical equivalence. Estimates using corrected V1RM more closely matched measured 1-RM (mean difference = -0.4 ± 6.8 kg; d = 0.06) and demonstrated statistical equivalence, with the 90% confidence interval contained within predefined equivalence bounds (±7.2 kg). CONCLUSION:Although 1-RM estimates derived from the corrected V1RM showed minimal average bias, interindividual variability persisted across both estimation methods, limiting the accuracy of 1-RM predictions at the individual level.

High force production depends on effective transmission of motor commands to spinal motoneurones, a capacity that declines with age. Although strength adaptations are often attributed to cortical mechanisms, subcortical pathways providing strong descending drive remain understudied. The reticulospinal tract, with its fast, widespread projections to motoneurones, is well positioned to support force generation, yet its role in human strength adaptation is largely unknown. This study examined age-related differences in corticospinal and reticulospinal adaptations following short-term strength training. Thirteen older adults (67 ± 5 years) and twelve younger adults (26 ± 6 years) completed a two-week unilateral elbow-flexor strength training programme. Neurophysiological and behavioural assessments were performed to evaluate cortical and subcortical activity and their contribution to strength gains. Both groups demonstrated similar increases in strength; however, corticospinal excitability decreased in younger adults and remained unchanged in older adults. Reduced GABAergic inhibition, indexed by shortened cortical silent periods, occurred in both groups. Reaction time and rate of force development in response to startling stimuli improved in both groups, with a more pronounced StartReact effect in older adults, consistent with enhanced reticulospinal responsiveness. Voluntary drive, measured by central activation ratio, increased significantly in older adults (p < 0.001), whereas MMAX remained stable. Early strength gains were accompanied by reduced intracortical inhibition and increased engagement of subcortical descending pathways. The pronounced StartReact responses and enhanced early-force kinetics provide indirect evidence of greater reticulospinal contribution, with older adults appearing to rely more heavily on this pathway when corticospinal plasticity is limited. Short-term strength training improved rate of force development and reaction time in older and younger adults. Corticospinal excitability decreased in younger adults after training, with no change in older adults, indicating age-related differences in corticospinal plasticity. GABAergic inhibition, as indexed by cortical silent period (cSP), was reduced in both groups following training.

High-intensity interval training (HIIT) and strength exercise (SE) induce corticospinal plasticity in exercised and non-exercised muscles. While HIIT's systemic neuromodulatory effects are well-established, SE's comparable remote responses remain unclear. This study investigated changes in corticospinal, intracortical, and spinal excitability, as well as motor performance, in non-exercised flexor carpi radialis following single-session HIIT and plantar flexion SE. Using a randomised crossover design, eighteen participants completed: (1) 20-minute high-intensity interval cycling, (2) high-intensity resistive plantar flexion, and (3) control. Corticospinal responses were assessed using transcranial magnetic stimulation and peripheral nerve stimulation; motor performance through reaction time tasks and maximum voluntary force at baseline and post-exercise. Only HIIT significantly increased motor-evoked potential amplitude (p = 0.002) and reduced short-interval intracortical inhibition (p = 0.04). HIIT reduced silent period duration compared to baseline and control (p <0.001), while SE showed reduction only versus control (p <0.001). Both HIIT and SE improved reaction time compared to baseline and control (p <0.05). These findings highlight differential corticospinal responses in a remote, non-exercised muscle, with HIIT inducing distributed excitability enhancements compared to SE. Unilateral, small-muscle SE may be insufficient to induce widespread corticospinal excitability changes, with implications for neurorehabilitation strategies targeting remote muscle groups.

BACKGROUND:Short-cycle antiretroviral therapy (ART), comprising 5 days on and 2 days off treatment, offers the potential for ART-free weekends, reduced toxicity, and improved quality of life for adolescents living with HIV, who typically have worse treatment outcomes than other age groups. We aimed to compare the efficacy and safety of short-cycle ART containing tenofovir disoproxil fumarate-lamivudine-dolutegravir with continuous ART in adolescents living with HIV in Africa. METHODS:We conducted an open-label, randomised, parallel, two-arm, non-inferiority trial (BREATHER Plus) in five clinical research centres across Kenya, South Africa, Uganda, and Zimbabwe. Adolescents (aged ≥12 years to <20 years) with an HIV-1 viral load of less than 50 copies per mL over the previous 12 months and no documented history of treatment failure were eligible for inclusion. Participants were randomly assigned (1:1) by use of permuted blocks to either short-cycle ART or continuous ART, stratified by clinical centre and mode of HIV acquisition (vertical vs horizontal or other). Participants received a daily oral fixed-dose combination of tenofovir disoproxil fumarate (300 mg), lamivudine (300 mg), and dolutegravir (50 mg); those assigned to short-cycle ART could choose their two consecutive days off (ie, Friday and Saturday or Saturday and Sunday). The primary outcome was confirmed viral rebound (the first of two consecutive viral load measurements ≥50 copies per mL) by week 96, analysed by intention to treat in all participants with viral load data after baseline assessment by use of adjusted Kaplan-Meier estimated proportions. The non-inferiority margin and confidence level depended on the event rate in the continuous ART group (an 8% margin with 99% CI for a 5% event rate). This trial is registered with ISRCTN (85058577), and follow-up is complete. FINDINGS:Between June 29, 2022, and May 10, 2023, 470 adolescents living with HIV were randomly assigned to either short-cycle ART (239 [51%]) or continuous ART (231 [49%]). 263 (56%) participants were female and 207 (44%) were male. Median follow-up was 117 weeks (IQR 108-120). 23 participants in the short-cycle ART group and 11 in the continuous ART group had confirmed viral rebound by 96 weeks, with an estimated probability of confirmed HIV-1 RNA of at least 50 copies per mL of 9·9% (95% CI 6·4-14·3) in the short-cycle ART group versus 4·8% (2·6-7·8) in the continuous ART group. With an estimated difference of 5·1% (99% CI -0·8 to 11·5; bootstrap p=0·034), an 8% higher rate of confirmed virological rebound in the short-cycle ART group was not rejected, and the rate of confirmed virological rebound was significantly higher in the short-cycle ART group than in the continuous ART group. By the end of follow-up, 16 serious adverse events in 15 participants were reported in the short-cycle ART group (including one death unrelated to HIV or ART) and 22 serious adverse events in 16 participants in the continuous ART group. INTERPRETATION:BREATHER Plus findings demonstrate that short-cycle ART with tenofovir disoproxil fumarate-lamivudine-dolutegravir should not be recommended for adolescents living with HIV receiving standard-of-care, routine viral load monitoring every 6-12 months. FUNDING:European and Developing Countries Clinical Trials Partnership, and UK Medical Research Council.

Background Alternatives to daily oral antiretroviral therapy (ART) are important for adolescents with HIV (AHIV) to improve adherence and outcomes. Long-Acting-injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) has demonstrated excellent efficacy and safety and strong patient preference in adults. Methods LATA is an ongoing randomised, open-label, 96-week, non-inferiority trial evaluating the efficacy, safety and acceptability of LAI CAB/RPV vs. daily oral therapy with tenofovir (disoproxil fumarate or alafenamide)/lamivudine/dolutegravir (TLD). Participants are virologically suppressed AHIV aged 12-

Modelling approaches that consider system-wide delivery platforms rather than single diseases can be instrumental in economic evaluation and forward-looking policy formulation. This study develops a costing approach tailored to the Thanzi La Onse (TLO) model of Malawi’s healthcare system, with general applicability to other health system models. We developed a mixed-method costing approach to estimate the total cost of healthcare delivery (excluding high-level administrative costs) in Malawi using the TLO model, from a healthcare provider perspective. Through iterative adjustments of key parameters, we aligned model-based estimates as closely as possible with real-world expenditure and budget data. Costs were projected for 2023–2030 under alternative scenarios of health system capacity. A comparison with expenditure and budget data suggests our costing method is broadly reliable for the conditions captured by the model, though some mismatches remain owing to data limitations and definitional inconsistencies. Under current system capacity, total healthcare delivery costs for 2023–2030 were estimated at 2.83 billion US dollars [95

The neural mechanisms underlying resistance training (RT) adaptations remain incompletely understood, particularly the contribution of cortico-reticular and reticulospinal tracts (RSTs), which have rarely been examined in humans. One factor that may critically shape these adaptations is training pace, an overlooked yet physiologically relevant variable, as externally paced and self-paced contractions impose distinct demands on cortical and subcortical motor circuits. This study examined (1) how RT affects RST excitability and (2) whether different types of RT produce distinct changes in descending motor pathway excitability. Thirty healthy participants were randomized to metronome-paced RT (MP-RT), self-paced RT (SP-RT) or control. Cortical and corticospinal excitability were assessed with transcranial magnetic stimulation, while cortico-reticulospinal and RST excitability were measured using the ipsilateral to contralateral motor-evoked potential amplitude ratio (ICAR) and the StartReact effect. Training consisted of dumbbell exercises performed three times weekly for three weeks, with repeated neurophysiological testing. Both RT protocols improved one-repetition maximum and maximal voluntary force (P < 0.001). SP-RT resulted in greater increases in the StartReact effect (P < 0.001), rate of force development (0.0453) and cortico-reticulospinal excitability (ICAR; P = 0.0351), whereas MP-RT elicited larger increases in corticospinal excitability (P = 0.00420) and greater reductions in short-interval intracortical inhibition (P < 0.001). This study provides the first evidence in humans that RT modifies cortico-reticular and RST excitability. Importantly, adaptations were pacing-dependent: SP-RT selectively targets cortico-reticular circuit and RST, whereas MP-RT engaged corticospinal and inhibitory intracortical circuits. This pathway-specific plasticity underscores training modality as critical determinant of neural adaptation, with implications for rehabilitation and performance. KEY POINTS: This study examined the effects of resistance training (RT) on descending motor pathways using transcranial magnetic stimulation and the StartReact protocol. Given the inaccessibility of the reticulospinal tract in humans, its excitability was inferred indirectly via the StartReact effect and ipsilateral to contralateral MEP amplitude ratio (ICAR), offering novel insight into cortico-reticulospinal modulation. Both metronome-paced and self-paced RT increased muscle strength but induced distinct neural adaptations. Self-paced RT engaged cortico-reticular and reticulospinal pathways, as indicated by elevated ICAR and StartReact effect values, while metronome-paced RT increased corticospinal excitability and reduced intracortical inhibition. These findings demonstrate, for the first time in humans, that RT pacing can differentially modulate corticospinal and reticulospinal excitability, two parallel descending motor systems with distinct roles. This selective pathway engagement suggests that training tempo is not merely behavioural but a physiologically meaningful factor for directing neuroplasticity.

BACKGROUND:Alternatives to daily oral antiretroviral therapy (ART) are important for adolescents with HIV (AHIV) to improve adherence and outcomes. Long-Acting-injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) has demonstrated excellent efficacy and safety and strong patient preference in adults. METHODS:LATA is an ongoing randomised, open-label, 96-week, non-inferiority trial evaluating the efficacy, safety and acceptability of LAI CAB/RPV vs. daily oral therapy with tenofovir (disoproxil fumarate or alafenamide)/lamivudine/dolutegravir (TLD). Participants are virologically suppressed AHIV aged 12- < 20 years in Kenya/South Africa/Uganda/Zimbabwe. Randomisation was 1:1 to LAI CAB/RPV given once every 8 weeks (after optional oral lead-in) or daily oral TLD. The primary outcome is viral rebound (two consecutive viral loads ≥50 copies/mL by 96-weeks). Viral loads are measured every 24 weeks. The trial employs the Smooth Away From the Expected (SAFE) non-inferiority frontier, where the non-inferiority margin depends on the observed event rate in the control arm. Secondary outcomes include confirmed viral load ≥200 copies/mL by 96-weeks, HIV resistance, safety, patient-reported outcomes and cost-effectiveness. LAI participants return to oral ART at confirmed viral load ≥200 copies/mL; LAI participants who become pregnant are given the choice to continue on LAI or to switch back to daily oral ART, with optional pharmacokinetic sampling during pregnancy and post-partum in both groups. Enrolment of 476 AHIV completed in April 2024. Results will be reported in 2026. CONCLUSION:LATA is the first trial comparing the efficacy, safety and acceptability of LAI CAB/RPV to oral ART in AHIV, enrolled in Sub-Saharan Africa, using a programmatic approach to viral load testing. TRIAL REGISTRATION:This trial has been registered with ClinicalTrials.gov (NCT05154747).

Ageing is associated with a decline in strength; however, the neural mechanisms underpinning these changes remain poorly understood. Motor unit discharge rate (MUDR) and recruitment threshold (MURT) regulate the magnitude of motoneuron output through rate coding and orderly recruitment, while discharge rate variability (MUDRV) reflects the steadiness of motoneuron output. Yet, age-related differences in these properties remain inconsistent across the literature. Therefore, this systematic review and meta-analysis quantified age-related differences in motor unit behaviours and their contribution to maximal isometric strength. Electronic databases (Medline, Embase, Scopus, PsycINFO, Ovid Emcare, CENTRAL, and Web of Science) were searched up to May 2025, yielding 1493 records; of these, 48 studies met the inclusion criteria. Standardised mean differences (SMDs) were calculated using random-effects models to compare older and younger adults, and methodological quality was assessed using the AXIS tool. Older adults exhibited markedly lower maximal strength than younger adults (SMD = -1.01; 95% CI -1.22, -0.79). MUDR was lower in older adults across all contraction intensities, with greater reductions at high forces (> 60% maximal voluntary contraction (MVC): SMD = -0.65; 95% CI -0.96, -0.34) compared to low forces (< 30% MVC: SMD = -0.34; 95% CI -0.50, -0.18). Discharge rate variability was greater (SMD = 0.44; 95% CI 0.15, 0.72), whereas recruitment thresholds relative to MVC were lower (SMD = -0.42; 95% CI -0.80, -0.03) in older adults. Collectively, these findings suggest that age-related alterations in motor unit discharge behaviour may contribute, at least in part, to reduced maximal strength in older adults.

Age-related declines in neuromuscular performance are well documented; however, the cortical processes underlying these changes remain unclear. This systematic review and meta-analysis compared younger and older adults across key transcranial magnetic stimulation measures of corticospinal and intracortical function, including corticospinal excitability, cortical silent period, intracortical facilitation and intracortical inhibition. Age-related differences in maximal voluntary strength were also quantified as a secondary outcome. A comprehensive literature search identified 52 eligible studies from 1682 records. Methodological quality was evaluated using a modified Downs and Black checklist, and the certainty of evidence was assessed using the GRADE approach. A random-effects model was applied to calculate standardised mean differences (SMDs) with 95% confidence intervals (CIs). Compared to younger adults, older adults produced lower maximal isometric voluntary force (SMD = -0.76) and exhibited reduced resting motor evoked potential amplitudes (SMD = -0.55) and intracortical facilitation (SMD = -0.27). These age-related differences were not observed during active contractions. Cortical silent period duration was longer in older adults (SMD = 0.39). No age-related differences were found in short- or long-interval intracortical inhibition. These findings indicate that ageing is associated with reduced resting corticospinal and intracortical excitability, prolonged cortical silent periods and lower maximal voluntary strength. As neural and strength outcomes were analysed independently, a causal relationship cannot be established, but the parallel pattern points to central neural alterations as plausible targets for future interventions aimed at mitigating age-related neuromuscular decline.

Global health initiatives have expanded access to HIV, tuberculosis, and malaria services in low-income countries, yet these programmes often operate within fragile health systems where shortages of healthcare workers and essential medicines limit their effectiveness and sustainability. Evaluating investments in health system capacity remains challenging because their benefits are difficult to attribute. Here, using a dynamic microsimulation model of Malawi’s health system, we show that health system strengthening investments alone could avert 11.4% of disability-adjusted life years between 2025 and 2035, delivering a return of $26.1 per dollar invested. Combining system strengthening with HIV, tuberculosis, and malaria programme expansion produces three times greater health impact than disease-focused investment alone, delivering a return of $11.7 per dollar invested compared with $5.4 for disease-focused expansion alone. These findings support a shift toward integrated global health financing strategies that combine health system strengthening with disease-targeted programmes. A modelling study of Malawi’s health system shows that combining health system strengthening with disease-targeted programmes delivers twice the return on investment and three times the health impact of disease-focused investment alone.

The latest hypothesis regarding the source of enhanced neural activation from resistance training is the reticulospinal rather than the corticospinal tract, based on invasive animal and emerging human data. The present study employed a six-week isometric resistance training intervention in a randomized controlled design to address this knowledge gap. Thirty-nine healthy, untrained males (age 23 y, sustained contraction group n = 13, explosive contraction group n = 9, control group n = 17) underwent neuromuscular and electrophysiological testing and completed all study requirements. Maximal isometric torque (MVC) and rate of torque development (RTD) were measured during a familiarization session as well as before and after the six-week period. Transcranial magnetic stimulation was used to assess motor-evoked potential (MEP) area and silent period duration while subjects contracted to 10

In Pakistan, every third adult is suffering from diabetes. Community-based approaches have the potential to be effective in preventing diabetes. We aim to evaluate the effectiveness of a Participatory Learning and Action (PLA) intervention in the prevention and control of diabetes. We will conduct a two-arm cluster randomised controlled-trial in two rural tehsils of district Swabi and district Peshawar in Pakistan. We will recruit 72 randomly selected clusters (the smallest official administrative unit in a tehsil) from two districts of the Khyber Pakhtunkhwa Province of Pakistan. From each cluster, 177 participants will be randomly selected for baseline and follow-up assessments, constituting a total sample size of 12,744. Following the baseline survey, the 72 clusters will be randomly allocated (1:1) to the intervention and control arms. The intervention arm will receive an 18-month long PLA intervention, including monthly community meetings where group members will identify, prioritise, and address problems associated with diabetes and the related risk factors. The primary outcomes of the trial are the prevalence of Type II Diabetes Mellitus (TIIDM), prevalence of Intermediate Hyperglycaemia (IHG), and 2-year cumulative incidence of TIIDM. Secondary outcomes include prevalence of hypertension, body mass index, abdominal obesity, prevalence of overweight obesity, body fat composition, fruit and vegetable intake, physical activity, quality of life, psychological distress, knowledge of TIIDM risk factors, symptoms, complications and self-awareness of diabetic status. Embedded economic and process evaluations will also be conducted. The trial has received ethics approval from the National Bioethics Committee of Pakistan, and the ethics committees of The Aga Khan University, and Khyber Medical University. We will use a variety of channels, conferences, social media, dissemination events, and scientific publications to share the study findings with all the relevant stakeholders. The trial is registered with clinicaltrials.gov—NCT06561126. Date of registration: 23rd August 2024.