Search Results (1,002)

Objective: This study assessed the blood-pressure effects of various exercise regimens in middle-aged and older adults with type 2 diabetes, considering baseline levels, to clarify dose–response relationships for personalized exercise guidance. Methods: We conducted a dose–response network meta-analysis. Systematic searches were performed in Web of Science, EMBASE, PubMed and Cochrane Library. Baseline blood pressure was modelled as an explanatory variable via meta-regression. Thirty-six eligible RCTs of physical-activity interventions in older adults with type 2 diabetes reporting blood-pressure outcomes were included. Results: In stage 1–2 hypertension, mind–body activities were associated with the greatest systolic blood-pressure reduction and appear to be the most effective intervention based on available evidence. For diastolic blood pressure, combined aerobic-resistance training was effective in stage 1 hypertension. Dose–response analysis indicated that clinically meaningful reductions occur at modest volumes (668 and 657 MET-min/week for systolic and diastolic pressures, respectively), aligning with the lower end of international activity guidelines. Conclusions: Individualized exercise prescription based on baseline blood pressure may offer a useful non-pharmacological strategy for hypertension management in older adults with type 2 diabetes. By quantifying the required activity dose, this work provides an evidence base for integrating structured exercise into precision care for this high-risk population. Full article

Crossfit^® is a high-intensity interval training modality that combines weightlifting, aerobic exercises, and gymnastics. Although it has gained widespread popularity, it also presents a considerable injury rate without clarity on the extent to which experience categories exhibit distinct temporal patterns. This study identifies the most common injuries and their progression across CrossFit^® categories over 12 months. We defined injury as any Crossfit-related event requiring healthcare consultation and interrupting an athlete’s activity. An observational, longitudinal study was conducted with 102 participants categorized into three groups (n = 34): beginner, scale, and rx. An adapted injury index questionnaire was applied, and descriptive statistics were performed. Results showed that the most frequent injuries affected the shoulder and knee, with variations across the different athlete categories. Beginners exhibited the highest injury rates: knee (56%) and shoulder (35%). The scale group presented a greater concentration of shoulder injuries, whereas rx demonstrated the lowest injury incidence overall. Over the 12-month follow-up, 135 injuries were reported at baseline, decreasing to 116 at six months and 101 at the final evaluation. Dropout rates were 35% among beginners, 12% in the scale group, and 0% in the rx group. Crossfit-related injuries primarily affect the shoulders and knees, with a higher incidence in beginners. Future studies should investigate movement technique, strength, mobility, and limb dominance considering the overhead demands and the associated injury risk, in addition studies should examine training programming too Full article

Exercise training improves maximum aerobic capacity, in part, through improvements in skeletal muscle function. This study aimed to investigate adaptations to improved aerobic capacity training through non-invasive and non-exhaustive tests of hyperemic muscle blood flow and near-infrared spectroscopy (NIRS) muscle oxygenation kinetics. An experimental study was conducted on 18 participants (age, 28.2 ± 5.3 yr; _absVO_2max, 3.60 ± 0.67 L·min⁻¹). Before and after the intervention of a 6-week of high-intensity interval training (HIIT), participants underwent three tests: (1) a graded cardiopulmonary exercise test; (2) a vascular occlusion test; and (3) a steady-state exercise (SSE) at 60% of PPO. Expired gas analysis, superficial femoral blood flow (occlusion test only) and SmO₂ kinetics were measured. The intervention increased maximal aerobic capacity _absVO_2max (p < 0.001, d = 0.65) and PPO (p < 0.001; d = 0.41). Moreover, steady-state _absVO₂ (p = 0.006; d = 0.37) and HR (p = 0.001; d = 0.65) were reduced. With the cuff test, the SmO₂ desaturation slope increased (p = 0.04; d = 0.52), while peak muscle blood flow (p = 0.02; d = 0.51) and the SmO₂ 10 s reoxygenation rate increased (p < 0.001 d = 1.11; 0.74 ± 0.28 to 1.17 ± 0.45%/s). During steady-state exercise, SmO₂ decreased less (p = 0.02; d = 0.43), and the 10s recovery kinetics rate was slowed (p = 0.01 d = 0.30; 0.28 ± 0.20 to 0.22 ± 0.21%/s). The improvement in VO_2max had a moderate correlation with the SmO₂ recovery rate post-steady-state exercise (p = 0.05, r = −0.54). HIIT changed maximal aerobic capacity alongside improvements in skeletal muscle hyperemic blood flow, SmO₂ post-occlusive reactive hyperemia and SmO₂ post-exercise recovery kinetics. Thus, the findings indicated that non-invasive and non-exhaustive hemodynamic kinetic profiles can monitor adaptations to improved aerobic capacity. Full article

Background/Objectives: Low-carbohydrate (LCD) and ketogenic diets (KD) are increasingly adopted by athletes due to their ability to enhance fat oxidation and induce metabolic adaptations. While their effects on aerobic power and capacity have been widely investigated, their influence on anaerobic performance remains unclear. Given the strong dependence of high-intensity exercise on glycolytic metabolism and muscle glycogen availability, carbohydrate restriction may have significant implications for short-duration maximal efforts and repeated high-intensity exercise. Therefore, this systematic review and meta-analysis aimed to evaluate the effects of LCD and KD on anaerobic performance outcomes in trained athletes. Methods: A comprehensive search of five electronic databases (PubMed, SCOPUS, Web of Science, SPORTDiscus, and Cochrane Central Register of Controlled Trials) identified 13 unique studies (yielding 15 study-level entries across three anaerobic performance domains) meeting comprehensive inclusion criteria. Individual study sample sizes ranged from n = 5 to n = 65 participants, reflecting substantial inter-study variability that should be considered when interpreting pooled estimates. Outcomes included peak and mean power output, repeated sprint performance, blood lactate responses, and markers of substrate utilization. Study quality was assessed using the Newcastle–Ottawa Scale, and meta-analyses were performed using random-effects models where appropriate. Results: Overall, the effects of carbohydrate-restricted diets on anaerobic performance were domain-specific. Some studies reported maintained or slightly improved peak power during single maximal efforts, while others showed no effect. Impairments were more consistently observed in repeated high-intensity exercise. Repeated sprint performance was impaired in several studies, likely reflecting reduced muscle glycogen availability and limited glycolytic ATP production. Carbohydrate restriction consistently increased fat oxidation and was associated with lower blood lactate concentrations during high-intensity exercise. Random-effects meta-analyses yielded domain-specific pooled effect sizes: maintained-to-slightly-improved anaerobic power output (Cohen’s d = +0.29; 95% CI: −0.08 to +0.66), modestly impaired repeated sprint ability (d = −0.33; 95% CI: −0.80 to +0.14), and a large, consistent reduction in blood lactate concentration (d = −0.89; 95% CI: −1.20 to −0.58). Given substantial between-study heterogeneity in intervention durations (2 days to 12 weeks), dietary composition, athlete populations, and outcome measures (1RM, Wingate, CMJ within the power domain; varied protocols within the RSA and lactate domains), these pooled estimates should be interpreted as exploratory rather than confirmatory. Conclusions: LCD and KD appear to have domain-specific effects on anaerobic performance in trained athletes. Although single, short-duration efforts may be preserved in some contexts, repeated, high-intensity performance appears to be more susceptible to impairment. These findings highlight the importance of aligning dietary strategies with the metabolic demands of training and competition. Full article

Combined functional training (FT), high-intensity interval training (HIIT) and aquatic exercise may improve health-related fitness in aging populations; however, the influence of baseline adiposity on training responses remains unclear. This study evaluated the effects of a 12-week multicomponent training program on aerobic capacity, body composition, metabolic health, and physical performance in middle-aged and older women and explored whether baseline body fat percentage modulated these responses. Thirty-four women (50–72 years) were assigned to a control group (Ctrl, n = 10) or an exercise group, stratified into normal fat (NF%, n = 10) and high fat (HF%, n = 14). The intervention included three weekly 60 min sessions consisting of HIIT, FT, and aquatic-based interval and resistance exercises, while controls maintained their habitual lifestyle without structured exercise. Significant improvements were observed in VO₂max, skeletal muscle mass, fasting insulin, triglycerides, total cholesterol, HDL cholesterol, and functional performance. Baseline adiposity influenced metabolic adaptations, with greater improvements in the HF% group. These findings suggest that multicomponent training may improve cardiometabolic health and physical performance; however, the results should be interpreted cautiously due to the quasi-experimental design and small sample size. Full article

Purpose: Recent studies have shown that high-intensity interval training (HIIT) can improve cardiometabolic health in individuals with spinal cord injury (SCI); however, many barriers remain for individuals with spinal cord injury to participate in exercise such as lack of time, accessible equipment and facilities, and transportation. The use of telehealth interventions may be a form of exercise delivery that can ease the burden on the participant and lead to greater exercise participation. Thus, the purpose of this study was to determine the feasibility and efficacy of a home-based telehealth HIIT arm crank exercise training program for individuals with spinal cord injury. Methods: Participants were randomly assigned to 16 weeks of telehealth HIIT arm crank exercise training or a no-exercise control group. Body composition, resting energy expenditure (REE), blood lipids, insulin sensitivity, blood pressure, aerobic capacity (VO₂ max), and a qualitative interview were assessed at baseline and at 16 weeks post intervention. Results: Six individuals (four male and two female, mean age 52.7 ± 10.2 years) with spinal cord injury were recruited for this study. Four out of five HIIT participants showed improvements in aerobic capacity, insulin sensitivity, and resting energy expenditure. Three qualitative themes emerged: (1) convenience and perceived benefits were critical elements of engagement; (2) high-intensity exercise elicited time-sensitive responses; and (3) trainers played a key role in promoting strong program adherence. Conclusions: Overall, we found that this program could be easily implemented and per-formed at home in individuals with spinal cord injury. We also found that participants enjoyed the 1:1 training sessions with a telecoach and that the intervention was easy to adhere to, as demonstrated by participant attendance. There is a need for future randomized controlled trials to determine the efficacy of telehealth exercise training for improving cardiometabolic health in spinal cord injury. Full article

Background: Working memory is essential for college students’ academic success, yet modern sedentary and digitally distracted lifestyles threaten cognitive health. This network meta-analysis compared the effectiveness of six exercise modalities on working memory in this population. Methods: Following PRISMA-NMA guidelines (PROSPERO: CRD420261331066), we systematically searched PubMed, Web of Science, Embase, Cochrane Library, SPORTDiscus, and CNKI for randomized controlled trials up to 13 February 2026. The primary outcome was reaction time on working memory tasks. We used frequentist random-effects network meta-analysis in Stata 18.0. Results: Thirty-five trials (2314 participants) were included. Compared to controls, significant benefits were found for aerobic exercise (SMD = −0.63, 95% CI: −0.94 to −0.32), mixed-modal training (SMD = −0.59, 95% CI: −0.92 to −0.26), HIIT (SMD = −0.56, 95% CI: −0.96 to −0.16), and resistance training (SMD = −0.48, 95% CI: −0.82 to −0.14). Ball sports and cognitive training showed no significant effects. HIIT and mixed-modal training ranked highest (SUCRA 80.3% and 76.0%). Chronic interventions (≥4 weeks) yielded larger effects than acute protocols. Direct comparisons among effective modalities revealed no significant differences. Conclusions: Aerobic-dominant exercise interventions were associated with moderate working memory improvements in college students, though the optimal type remains uncertain pending further comparative trials. Full article

Tyrosol, a phenolic compound derived from olive products, exhibits anti-inflammatory, neuroprotective, and cardiometabolic properties, whereas creatine is a well-established ergogenic aid with documented benefits for muscular performance and emerging evidence for cognitive support. This 5-week randomized, double blind, placebo-controlled trial examined the effects of Tyrosol, creatine, their combination, and placebo on resistance and aerobic exercise performance and psychomotor vigilance in healthy adults. Participants (n = 48; 18–50 years) consumed their assigned supplement for 4 weeks, after which changes in upper and lower body strength, submaximal resistance performance, aerobic capacity, lactate responses, plyometric performance, and acute cognitive function were assessed. The Tyrosol + Creatine condition produced the most consistent improvements in upper body resistance performance, particularly for higher load, higher volume bench press work. In contrast, neither the Tyrosol-alone group, the creatine-alone group, nor the placebo group achieved this effect, which suggests there is a synergistic effect between Tyrosol and creatine. No significant effects were observed for intermediate resistance loads, isometric lower body strength, grip strength, aerobic endurance, lactate responses, plyometric outcomes, or acute psychomotor vigilance. Collectively, these findings support the use of short-term co-supplementation with Tyrosol and low-dose creatine (without a loading phase) as a potentially beneficial strategy to enhance upper-body training quality in specific tests and improve upper-body strength endurance. Full article

Allergic Rhinitis (AR) is an IgE-mediated inflammatory disorder that impairs quality of life and systemic function. Following the ‘one airway, one disease’ paradigm, AR-related inflammation often extends to the lower respiratory tract. This randomized controlled trial investigated the effects of an 8-week moderate-intensity aerobic exercise (MOA) program on clinical symptoms, nasal airflow, airway inflammation, pulmonary function, and cardiorespiratory parameters in young adults with physician-confirmed persistent AR. To isolate the exercise effects, all participants discontinued antihistamines, corticosteroids, and leukotriene antagonists before and during the study period. Eighteen participants were allocated to either the MOA group (n = 9), which performed treadmill walking or jogging at 50–60% heart rate reserve three times per week for eight weeks, or a control group (CON, n = 9) that maintained usual daily activities. Clinical symptoms, peak nasal inspiratory flow, fractional exhaled nitric oxide, pulmonary function, heart rate, blood pressure, aerobic fitness, and perceived exertion were assessed at baseline, week 4, and week 8 using standardized procedures. Compared with baseline and the CON group, the exercise intervention resulted in significant reductions in nasal congestion, itching, sneezing, and rhinorrhea, accompanied by increased nasal airflow and reduced airway inflammation. Pulmonary function indices and cardiorespiratory parameters also improved following training. These findings suggest that moderate-intensity aerobic exercise may offer a valuable non-pharmacological approach to support conventional care, potentially enhancing respiratory and physiological outcomes in young adults with persistent AR. Full article

Cognitive frailty (CF), characterized by concurrent cognitive and motor decline, is a major challenge to healthy aging, yet effective interventions remain limited. Klotho, an anti-aging protein that declines with age, has been implicated in both hippocampal function and skeletal muscle homeostasis. In this study, we investigated whether aerobic exercise combined with multisensory stimulation training (CT) ameliorates age-related CF through systemic Klotho signaling. A 16-month-old mouse model of age-related CF was assigned to aerobic training, multisensory stimulation, or combined training, and behavioral, electrophysiological, histological, and molecular assessments were performed. To examine the mechanistic role of Klotho, dual-route shRNA delivery was used to inhibit systemic Klotho expression. CT significantly improved cognitive and motor performance compared with either intervention alone. CT also increased hippocampal dendritic spine density and long-term potentiation, reduced collagen deposition in gastrocnemius muscle, and upregulated Klotho, FGF19, and FGFR1 expression in both hippocampus and muscle, accompanied by elevated serum Klotho levels. Klotho knockdown attenuated these beneficial effects, reduced PSD95 and GluN2B expression, and increased MuRF3 and TNF-α levels. These findings suggest that CT alleviates cognitive frailty and that systemic Klotho is a key mediator linking hippocampal synaptic function and skeletal muscle homeostasis. Full article

Background/Objectives: Understanding the available interventions and circumstances under which physical therapy is administered to patients with diabetic foot ulcers is important to provide more evidence regarding physical therapy and associated outcomes in this population. This study aimed to investigate the scope, nature, and extent of literature on physical therapy interventions for adults with diabetic foot ulcers. Methods: Articles on physiotherapy interventions for adults with diabetic foot ulcers published up to 30 June 2024 were included. Relevant articles were identified through searches of PubMed, Scopus, MEDLINE, and the Cochrane Library databases. Opinion articles, study protocols, meeting abstracts, and articles that did not describe physical therapy interventions were excluded. Results: The systematic search identified 13 articles that met the inclusion criteria. Eleven of the 13 articles were specifically related to outpatient physical therapy. Outpatient physiotherapy included unloading gait instruction, ankle stretching instruction, progressive resistance training, and aerobic exercise. In two other cases, exercise instructions were practiced in the early postoperative period of the wound during the hospitalization period. A multidisciplinary approach aimed at improving postoperative activities of daily living was included. The main efficacy indices were the wound reduction rate, plantar pressure reduction, hemodynamics, ankle joint range of motion, walking ability, and other physical function-related parameters. Conclusions: Physiotherapy during outpatient follow-up may contribute to preventing wound deterioration and maintaining physical function in patients with stable DFUs. However, standardized protocols regarding intervention timing, exercise intensity, and wound severity remain unestablished, and interventions should be applied cautiously based on individual clinical conditions. Full article

Background/Objectives: Aging is closely associated with sarcopenia, which has a significant impact on muscle mass and its function. Protein supplementation (PS) brings benefits such as lean mass and strength gains during exercise training. This paper determined the optimal regimen among the composites of variate protein sources and training modalities for older individuals. Methods: We comprehensively searched the electronic databases, namely MEDLINE Complete, PEDro, the Cochrane Library, Google Scholar, EMBASE, and the China National Knowledge Infrastructure, from its inception until December 2025. We included randomized controlled trials (RCTs) that examined the effectiveness of any type of PS combined with one of three exercise types—resistance, aerobic, or multicomponent training—in untrained older adults. The main outcomes used to identify sarcopenia were assessed, including lean mass, handgrip and leg strength, and physical mobility measures. Network meta-analysis (NMA) was performed by a frequentist method using random-effects models. The estimated treatment effect was expressed as the standard mean difference (SMD) with a 95% confidence interval (CI). Any potential factor moderating the treatment effect was determined by the meta-regression analyses, including participant characteristics and methodological factors. Certainty of evidence (CoE) was assessed by the GRADE framework. Results: In total, we included 235 RCTs (20,980 participants) for analyses. A total of 10 protein sources (whey, soy, casein, milk, and the others) were identified, corresponding to 24 monotherapy and combined regimens of PS and exercise. Among the treatment arms, whey plus resistance training was ranked as the most effective treatment for muscle mass (large SMD, 1.29; CoE, moderate) and leg strength (large SMD, 1.16; CoE, moderate); additionally, whey plus multicomponent exercise training achieved the most promising effects on such sarcopenia-related physical indicators such as chair rise (large effect, SMD = 1.09; CoE: high), timed up and go (medium SMD, 0.70; CoE, high), and global mobility score (large SMD, 1.02; CoE, high). Conclusions: The treatment efficacy appears to be moderated by the participant’s conditions, PS resource, and PS dose, particularly the outcome of muscle mass and strength. The present NMA results indicate that whey protein incorporated with resistance training is the optimal program to help combat sarcopenia in older adults. Full article

Objective: The goal was to investigate the relationship between methodological adherence and clinical outcomes in Progressive Resistance Training (PRT) for Parkinson’s Disease (PD), specifically identifying why findings of “superiority” over active controls remain inconsistent. Methods: This umbrella review utilized a multi-stage process to identify a sample of the primary literature for methodological analysis. An initial search identified 38 systematic reviews published within the specified timeframe. From the reference lists of these reviews, a subset of 34 primary clinical studies was purposefully selected. Inclusion was prioritized for studies providing comprehensive methodological data on PRT protocols and standardized clinical outcomes. Interventions were evaluated using a three-tiered framework: (1) training protocol with specifications of Frequency, Intensity, Time, Type, Volume, and Progression (FITT-VP) (General Exercise), (2) FITT-VP integrated with the American College of Sports Medicine (ACSM) Supplementary Guidelines (Integrated Guidelines), and (3) principles of progression (mechanistic growth). Studies were categorized by control type (active (e.g., aerobic or balance), n = 26; passive (e.g., standard care or no exercise), n = 8). Results: In trials that compared PRT with an active control group, PRT achieved clinical superiority in 57% (n = 15) of trials and 46% (n = 12) when focusing on trials with an effect on specific functional or balance outcomes. Among these successful interventions, 75% maintained high adherence (≥70%) to the Integrated Guidelines, and 58% maintained high adherence to the principles of progression. In the 53% (n = 14) of studies where PRT was found non-superior (equivalent or inferior in functional or balance outcomes) to an active control, 0% met the high adherence threshold for progression. While general FITT-VP compliance remained high (78%), the failure to implement systematic load, specificity, and variation served as a definitive barrier to competitive superiority. In the 100% of studies where PRT outperformed passive controls, high progression was present in 57% of cases. This may suggest that while a baseline resistance stimulus outperforms inactivity, it is fundamentally insufficient to outperform other active clinical therapies. Conclusions: This umbrella review indicates that adherence to the principles of progression may be an important factor influencing the clinical outcomes of PRT in individuals with PD. The variability observed in the current literature suggests that inconsistent application of established exercise frameworks—rather than the failure of the modality itself—could be a contributing element to the reported “inconclusiveness.” To potentially enhance functional outcomes and the comparative effectiveness of PRT, future research should consider prioritizing structured adherence to FITT-VP, Integrated Guidelines, and progression-based frameworks. Establishing a 70% adherence threshold is proposed as a potential benchmark to improve protocol consistency and support rehabilitation efficacy in this population. Full article

Background: Long-term methamphetamine use disrupts brain function and impairs cognition. Currently, there is a lack of effective treatments for cognitive dysfunction in this population. This study aimed to investigate the effects of different exercise interventions on cognitive function and brain activation in methamphetamine-dependent individuals and to explore the potential neural mechanisms underlying cognitive improvement. Methods: In this randomized, assessor-blind, controlled study, 162 male methamphetamine-dependent individuals in compulsory isolation were randomly assigned to one of four groups: traditional regimen training (TR, n = 41), aerobic exercise (AE, n = 40), multimodal cognitive exercise training (MC, n = 40), and a control group (MA, n = 41). All participants completed an 8-week intervention. Cognitive function was assessed before and after the intervention using the Stroop task, while fNIRS was used to measure task-related hemodynamic responses. In addition, the Memory and Executive Screening (MES) and choice reaction time tests were used to evaluate cognitive and psychomotor performance. Results: After 8 weeks, traditional regimen training (p = 0.006), aerobic exercise (p = 0.024), and multimodal cognitive exercise training (p < 0.001) all significantly improved Stroop task accuracy. Aerobic exercise significantly increased activation in L-DLPFC (p = 0.044), R-DLPFC (p = 0.036), and L-FPA (p = 0.038), improved MES-T scores (p < 0.001) and shortened choice reaction time (p < 0.001). Traditional regimen training increased L-DLPFC activation (p = 0.026), improved MES-T scores (p < 0.001), and shortened choice reaction time (p < 0.001). Multimodal cognitive exercise training increased activation in L-DLPFC (p = 0.006), R-DLPFC (p = 0.014), and L-FPA (p = 0.002), improved MES-T scores (p < 0.001) and shortened choice reaction time (p < 0.001). Conclusions: Cognitive impairment in methamphetamine-dependent individuals may be associated with reduced prefrontal functional activity. Different exercise modalities produced different patterns of cognitive improvement and brain activation, with multimodal cognitive exercise training showing the largest overall benefit. Full article

Background: Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by fluctuating skeletal muscle weakness and fatigue, leading to reduced functional independence and impaired quality of life (QoL). Although exercise has historically been discouraged due to concerns about symptom exacerbation, emerging evidence suggest that structured exercise programs may be safe and beneficial in clinically stable patients. This systematic review critically evaluates current evidence on exercise and physical activity interventions in MG, focusing on effectiveness, safety, and impact on functional outcomes, fatigue, and QoL. Materials and Methods: A systematic review was conducted following PRISMA guidelines. Searches were performed in PubMed, Web of Science, Google Scholar, Scopus and ScienceDirect for studies published between 2015 and 2025. Keywords included MG, physical activity, aerobic training, resistance training, and respiratory muscle training. Methodological quality was assessed using the Downs and Black checklist. Results: Eight controlled studies met the inclusion criteria, encompassing aerobic, resistance, combined, and respiratory muscle training interventions. Sample sizes ranged from small pilot studies to moderate-size randomized controlled trials. Overall, exercise interventions were well tolerated, with no evidence of sustained symptoms exacerbation. Aerobic and combined programs consistently improved functional capacity, muscle strength, and activities of daily living. Respiratory muscle training demonstrated improvements in pulmonary function and inspiratory muscle strength, although findings were more heterogeneous. Study quality ranged from poor to excellent, with common limitations including small sample size, short follow-up duration, and heterogeneity in exercise programs. Conclusions: Current evidence supports the safety and potential efficacy of individualized, symptom-guided exercise interventions in clinically stable MG. Regular physical activity exercise may reduce secondary deconditioning, improve functional outcomes, and enhance QoL. However, larger, high-quality randomized controlled trials with standardized programs and longer follow-up periods are required to strengthen clinical recommendations and clarify long-term effects. Full article