Background Individuals with anterior cruciate ligament reconstruction (ACLR) demonstrated neurological adaptations, but it remains unclear how these changes evolve from rehabilitation to return to sport (RTS) and how they affect quadriceps neuromuscular weakness. Therefore, this review aims to: (a) compare the activation in the cerebral cortex as well as the corticospinal and spinal tract of quadriceps between individuals with ACLR and healthy controls; (b) determine the effects of the neurological alterations on quadriceps neuromuscular function during rehabilitation and RTS. Methods A systematic search was conducted across PubMed, Web of Science, Medline, and SPORTDiscus. Risk of bias was assessed by the Methodological Index for Non-randomized Studies checklist and Egger’s test. The evidence certainty was evaluated by the Grading of Recommendations Assessment, Development, and Evaluation guidelines. Participant characteristics, time of data collection, the stage of rehabilitation (<12 months post-ACLR) or RTS (≥12 months post-ACLR), data on neurological measures (cortical activation, corticospinal and spinal excitability), data on quadriceps neuromuscular function (strength, rate of torque development (RTD), central activation ratio (CAR)), and relevant results in individual studies were extracted and synthesized in a narrative or quantitative format. Results Twenty studies involving 504 individuals with ACLR and 362 healthy controls were included, with certainty levels rated low to very low. Compared to healthy controls, individuals with ACLR exhibited increased active/resting motor threshold (AMT/RMT) in the nonsurgical limb only (standardized mean difference (SMD) = 0.64, p = 0.009), comparable interval intracortical facilitation and short interval intracortical inhibition, bilateral increased motor evoked potential (MEP) amplitudes (surgical: SMD = 0.71, p = 0.02; nonsurgical: SMD = 0.32, p = 0.03), and comparable H-reflex/M-wave ratio (H/M ratio), with the MEP amplitudes negatively associated with quadriceps strength during rehabilitation. At RTS, individuals with ACLR presented greater activation in frontal and parietal regions in the brain cortex contralateral to the surgical limb during knee flexion/extension movements, increased AMT/RMT (SMD = 0.73, p = 0.003) and H/M ratio (SMD = 0.33, p = 0.0009) in the surgical limb, with a negative association between AMT/RMT and quadriceps CAR. Conclusion Individuals with ACLR demonstrate bilateral corticospinal maladaptations in the quadriceps during rehabilitation (<12 months post-ACLR), and the alterations in the cortical, corticospinal, and spinal excitability in the surgical limb remain unresolved at the time of RTS (≥12 months post-ACLR). These neurological alterations are associated with quadriceps neuromuscular function, which underscores the importance of incorporating bilateral neurophysiological interventions and assessments into rehabilitation protocols and RTS criteria to improve the outcomes of ACLR.
A substantial body of research provides compelling evidence that tai ji quan, a mind-body exercise rooted in traditional Chinese medicine, is effective in reducing falls and improving mobility and has gained increasing recognition as a form of evidence-based exercise medicine within mainstream healthcare. Despite this strong evidence base and growing policy support, the translation of tai ji quan from research into routine clinical practice remains limited. Addressing this evidence-to-practice gap will require innovative translational strategies that more effectively integrate evidence-based tai ji quan with evolving models of healthcare delivery and emerging digital health technologies. This article reviews the current state of tai ji quan research in falls prevention and proposes an integrated translational roadmap to advance its adoption as a routinely prescribed, clinically embedded, technology-driven intervention. The roadmap is built upon 3 interrelated pillars: embedding tai ji quan within routine clinical workflows, expanding evidence generation through decentralized virtual trial designs, and augmenting implementation through responsibly governed artificial intelligence (AI)-enabled tools and systems. The framework presented may also serve as a generalizable model for applying evidence-based exercise medicine to the prevention, treatment, and management of other chronic conditions associated with aging.
BACKGROUND:Age-related impairments in thermoregulatory and cardiovascular function contribute to a heightened vulnerability to heat-related morbidity and mortality. While passive heat acclimation is highly effective at improving heat loss mechanisms in older adults, its effects on autophagic regulation remain unknown. Given autophagy represents a critical cellular survival mechanism and declines with advancing age, we sought to assess whether short-term passive heat acclimation via warm-water immersion modulates autophagic regulation and accompanying cellular stress pathways in older adults. METHODS:Twelve healthy older males (median interquartile range (IQR): 68 (64‒73) years) completed 7 days of passive heat acclimation via warm-water immersion (∼40°C), with core temperature maintained at 38.5°C for 60 min. Before and after acclimation, participants completed an exercise-heat stress test in 40°C (∼13% relative humidity) consisting of three 30-min cycling bouts (150, 200, and 250 W/m2), each separated by 15-min rest. Changes in protein content and gene expression were assessed in peripheral blood mononuclear cells (PBMC) before and after each exercise-heat stress test, as well as Days 1, 4, and 7 of the acclimation protocol. RESULTS:Across acclimation days, microtubule-associated light chain 3B (LC3)-II, LC3-II/I ratio, and lysosome-associated membrane protein-2A proteins progressively increased (p ≤ 0.019), while sequestosome-1/p62 decreased (p = 0.003), consistent with enhanced autophagic activity. Conversely, apoptotic-related cleaved-caspase-3 progressively declined with acclimation (p = 0.004). Post-acclimation exercise-heat stress responses elicited greater elevations in protein and gene markers of autophagy, as well as reduced apoptotic responses. CONCLUSION:Short-term passive heat acclimation increased PBMC markers associated with autophagy while reducing markers of apoptotic signaling in healthy, active older males.
BACKGROUND:Male breast cancer is a rare but increasingly recognized disease with limited data on modifiable risk factors. Specifically, it is not known if the inverse association between cardiorespiratory fitness (CRF) and breast cancer risk reported in women is similar to the association between CRF and breast cancer in men. The study aimed to evaluate the association between CRF and the incidence of male breast cancer in a large, nationally representative cohort of U.S. Veterans. METHODS:We analyzed data from 777,618 male Veterans who completed an exercise treadmill testing (ETT) between 1999 and 2024 within the Veterans Health Administration and had no evidence of breast cancer prior to the ETT. CRF was expressed in peak metabolic equivalents (METs). The cohort was categorized into 4 age-adjusted CRF categories based on the peak METs achieved. The primary outcome was incident male breast cancer, ascertained through the Veterans Affairs Computerized Patient Record System. Cox proportional hazards models were used to estimate hazard ratios (HRs) for breast cancer incidence across CRF categories, adjusted for age, race, body mass index, hypertension, diabetes (T2DM), chronic kidney disease, smoking, and alcohol use. RESULTS:Over a median follow-up of 10.7 years 518 men were diagnosed with breast cancer. After multivariable adjustment, age (HR = 1.24, 95% confidence interval (95%CI): 1.14-1.36) per decade, chronic kidney disease (HR = 2.13; 95%CI: 1.41-3.23), hypertension (HR = 1.57; 95%CI: 1.28-1.92), T2DM (HR = 1.24; 95%CI: 1.02-1.51), and poor CRF (HR = 1.69; 95%CI: 1.24-2.30) were the strongest predictors of breast cancer. Compared to patients in the lowest CRF category, breast cancer risk was 41% lower for individuals in the highest CRF quartile (HR = 0.59; 95%CI: 0.44-0.81). CONCLUSION:Higher CRF was independently associated with a substantially lower risk of breast cancer in men. These findings suggest that CRF may represent a modifiable risk factor in the prevention of male breast cancer, underscoring the broader importance of physical fitness in reducing cancer risk across sexes.
BACKGROUND:Wearable activity monitors are widely used to measure daily step counts, a simple and health-relevant metric of physical activity. However, differences in sensor technologies, algorithms, and wear locations across devices can result in substantial variability in step count estimates, creating challenges for comparing and harmonizing data across studies and populations. This study aims to compare free-living daily step counts across commonly used activity monitoring devices in adults using network meta-analysis. METHODS:We systematically searched PubMed, Scopus, and PsycINFO through November 2025 for studies reporting concurrent daily step measurements using at least 2 devices from our target list of 13 manufacturers of research- and consumer-grade accelerometers and pedometers. Network meta-analysis estimated the ratio of means (ROMs) and mean differences in daily steps between devices. RESULTS:Across 59 studies, most consumer devices, pedometers, and the thigh (ActivPAL) and hip-worn research devices (ActiGraph GT, Axivity, and Actical) were within 10% ROM and <700 steps/day. Wear location was the primary source of variation, with wrist-worn and ankle-worn (StepWatch) research-grade accelerometers estimating 15‒30% more daily steps (+1000 to 2200 steps/day) than hip-worn devices, while consumer-grade wrist devices showed smaller differences (3‒15% higher or +200 to 1000 steps/day). CONCLUSION:These findings provide researchers with evidence-based guidance for selecting appropriate step devices, interpreting step count data across studies, and considerations when combining data from multiple device types and wear locations.
BACKGROUND:Excessive exposure to sedentary behavior (SB) is associated with cognitive decline and impaired brain health; however, the neurobiological mechanisms underlying this relationship remain unclear. Functional near-infrared spectroscopy (fNIRS) enables real-time monitoring of cerebral hemodynamics in naturalistic settings and offers unique technical advantages for understanding the effects of SB on brain health. Notably, methodological standardization specific to SB research is lacking, limiting cross-study comparisons and evidence synthesis despite established general fNIRS best practices. METHODS:Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched PubMed, Scopus, Web of Science, and PsycINFO through February 2026 for studies using fNIRS to assess SB's effects on brain function. Two independent reviewers conducted study selection, data extraction, and bias risk assessment. We systematically extracted and analyzed instrumentation specifications, spatial positioning, data processing pipelines, statistical methods, and quality control measures to identify methodological variations and best practice patterns in current research. RESULTS:From 36,477 initial records, 43 studies encompassing 2751 participants were included. Study types comprised acute (25 studies) and chronic interventions (8 studies) manipulating or monitoring SB patterns as well as cross-sectional studies (10 studies) analyzing the association between SB patterns and fNIRS-related parameters. Substantial heterogeneity was evident for specific methodological aspects, such as the use of diverse fNIRS systems and sampling rates (e.g., spanning 1.81-50.00 Hz), whereas others such as source-detector separation (i.e., 3.0 cm) were relatively homogenous across studies. Critical methodological issues included inadequate reporting of spatial registration and data quality control procedures, inconsistent implementation of multiple comparison corrections, and neglected monitoring of relevant environmental factors and physiological confounds. CONCLUSION:This review provides the first SB-specific standardized methodological framework for fNIRS applications, building on established fNIRS best practices and extending them to address unique challenges of SB research, encompassing 6 core domains: hardware configuration, extended monitoring protocols, data processing, statistical analysis, quality assessment, and SB-specific reporting. Recommendations are systematically classified by evidence level, distinguishing minimum reporting standards applicable across all laboratories from best practices and aspirational approaches for well-resourced settings. Minimum recommendations include reporting optode geometry and placement with sufficient detail for replication and, where feasible, using short-separation regression (or a clearly justified alternative) to mitigate systemic physiological confounds. These recommendations aim to enhance methodological rigor, promote cross-study comparability, and support the long-term goal of identifying SB-related neurobiological biomarkers.
BACKGROUND:The American College of Sports Medicine (ACSM) provides recommendations for exertional heat illness risk assessment in different environmental conditions. The objectives of this study were to explore the thermal and cardiovascular responses of individuals performing self-paced running time trials equal to or greater than 5 km in different environmental risk categories, as determined by the ACSM extreme heat policy. METHODS:MEDLINE, PubMed, Scopus, and SPORTDiscus were systematically searched. Eligible studies included self-paced running (of at least 5 km) and reported core temperature and environmental conditions. Studies were sub-grouped according to the ACSM risk categorization (low/green (≤22.2°C Wet-bulb globe temperature (WBGT)), moderate/yellow (22.3‒25.6°C, WBGT), high/orange (25.7‒27.8°C, WBGT), or very-high/red (≥27.9°C, WBGT)). Meta-analyses (for each risk category) for pooled aggregate data were conducted using the common-effect inverse-variance model followed by a meta-regression to identify statistical differences between the risk categories. RESULTS:Forty-three studies (48 participant groups) were included with environmental risk conditions ranging from low, moderate, high, and very-high. The high-risk category had the highest end core temperature (39.50°C; 95% confidence interval (95%CI): 39.44‒39.55°C), although only the low and high risk groups were significantly different (p = 0.026). Skin temperature was significantly greater in all risk groups when compared to low risk (all p ≤ 0.008) and highest in the very-high risk category (35.46°C; 95%CI: 35.38‒35.55°C). High risk resulted in a significantly greater heart rate (185 beats/min; 95%CI: 184‒186 beats/min; p = 0.022) than moderate (181 beats/min; 95%CI: 180-182 beats/min) risk. Percentage body mass loss was highest in the very-high risk group (1.8%; 95%CI: 1.7-1.9%), but there was not a significant difference between the risk groups (all p > 0.05). CONCLUSION:Descriptive meta-analyses revealed that the thermoregulatory and cardiovascular strain was typically greater in the higher risk categories. However, risk thresholds were not consistently distinct according to the meta-regressions for core temperature, heart rate, % body mass loss, and time-trial performance.
BACKGROUND:Reduced high-density lipoprotein cholesterol (HDL-C) is a hallmark metabolic abnormality in metabolic syndrome (MetS). Exercise is widely recommended to improve HDL-C, but the optimal modality and dose remain uncertain. METHODS:This systematic review and network meta-analysis (NMA) followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane guidelines and was prospectively registered in PROSPERO (CRD420251049084). Five databases were searched through November 17, 2025. The NMA compared continuous aerobic exercise (CAE), high-intensity interval training (HIIT), resistance training (RT), combined aerobic-resistance exercise (CAREX), and mind-body exercise (MBE). Dose-response NMA (DR-NMA) using restricted cubic splines modeled multidimensional exercise doses derived from metabolic equivalent of task (MET)-min/week, % maximal oxygen uptake (VO₂max), and % 1-repetition maximum (1RM). RESULTS:Fifty-six randomized controlled trials comprising 3788 individuals with MetS were included. HIIT ranked as the most effective modality for raising HDL-C, with the highest surface under the cumulative ranking curve value (SUCRA = 86%), producing an increase of 0.08 mmol/L when performed at 750-1500 MET-min/week and 80-90% VO₂max, whereas higher volumes (≥1750 MET-min/week) or lower intensities (<60% VO2max) attenuated the benefit. CAREX increased HDL-C by 0.07-0.10 mmol/L at 750-2000 MET-min/week, combining 70-80% VO₂max aerobic work with 60-80% 1RM resistance loading. RT alone yielded only modest improvements (≈0.03-0.04 mmol/L) at ≥80% 1RM, with unfavorable responses at moderate loads (60-70% 1RM). CAE increased HDL-C modestly (≈0.04 mmol/L) at 65-75% VO2max, while higher intensities were associated with reductions. MBE did not produce meaningful HDL-C improvement and was associated with a small decrease (≈-0.08 mmol/L) at very high volumes. Across all modalities, HDL-C increased from 600 MET-min/week (0.05 mmol/L), peaked at 1070 MET-min/week (0.09 mmol/L), and diminished thereafter; intensity-based analyses further indicated optimal HDL-C responses at approximately 80% VO2max (0.11 mmol/L) and 80% 1RM (0.04 mmol/L). CONCLUSION:Exercise effectively improves HDL-C in individuals with MetS, with HIIT and CAREX offering the greatest benefits. Clear optimal dose ranges were identified across physiological load indicators, underscoring the need for individualized, dose-precise exercise prescriptions to optimize HDL-C improvement.
