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PubMed2026

Acute Performance, Mechanical and Thermal Effects of Isometric Conditioning Versus Standardized Volleyball Pre-Training Activation in Highly Trained Male Players.

This study compared acute performance, neuromuscular, and thermal responses to a maximal isometric conditioning activity (ICA) versus a standardized volleyball pre-training activation (VPA) in highly trained male volleyball players, and to explore putative mechanisms underpinning post-activation performance enhancement (PAPE) considering training load. In a randomized crossover, 14 men (27 ± 3 y) completed two sessions: VPA (mobility/plyometric drills; 9 min), and ICA comprising 3×5×3-s maximal isometric back-squat contractions (knee angle 120°; 3-min inter-set rest). Countermovement jump (CMJ) height (primary), relative peak power (PP), RSImod, and contraction time (CT) were recorded pre and 3, 6, 9, and 12 min post. Rectus femoris muscle viscoelastic properties and skin surface temperature (SST) were assessed at matched time points. Analyses used repeated-measures ANOVA, responder analysis, correlations, and regression. Period×Sequence interactions favored ICA for CMJ and PP when delivered in Period 2 (lower training volume): ∆CMJ was higher under ICA versus VPA (p = 0.005, d = 1.20); PP likewise greater (p = 0.026, ηp2 = 0.35). ICA yielded more beneficial responders than VPA (9/14 vs 1/14; McNemar exact p = 0.021). In Period 2, reductions in rectus femoris muscle stiffness independently predicted CMJ gains (β_std = -0.495, p = 0.005), whereas SST changes did not (p = 0.974). RSImod and CT showed no differences. A brief, high-effort isometric squat protocol was associated with superior acute improvements in jump performance compared with a standard volleyball warm-up, but this advantage emerged specifically when the preceding training volume was reduced (Period 2), suggesting that residual fatigue from training may reduce the effects of PAPE. Gains align with neuro-mechanical rather than thermal mechanisms, supporting ICA as a practical, equipment-minimal priming strategy for elite volleyball.

Humans↗

PubMed2026

Retrosigmoid craniotomy surgical guide: The way forward for precise exposure of the transverse-sigmoid sinuses.

INTRODUCTION: The retrosigmoid craniotomy is the workhorse approach to the cerebellopontine angle. Accurate localisation of the transverse-sigmoid junction (TSJ) is key for optimised exposure and cerebellar retraction. Various methods, both anatomical and navigational, have been used but with suboptimal results. We utilised a 3D-printed retrosigmoid surgical guide in an attempt to overcome this and report our early outcomes and experiences in the design, production and utilisation of the guide. METHODS: This is a prospective cohort study of the patients with retrosigmoid craniotomies performed using the surgical guides. Patient demographics and diagnoses, along with the accuracy of the planned burrhole and craniotomy, need for craniotomy extension, presence of venous sinus injury, set-up time, and cost were reported. RESULTS: There were ten cerebellopontine angle cases in which the surgical guides were utilised, three petrous meningiomas, two trigeminal neuralgias, two metastasis, and three other tumours. The planned burrhole and craniotomy were precise in all cases with accurate exposure of the TSJ and no requirement for craniotomy extension. The mean set up time was 3.9 min, and the mean cost of the surgical guides was USD 470.90. One elderly patient had an intraoperative transverse sinus injury related to adherent dura that was planned for exposure. CONCLUSION: The 3D-printed surgical guide is a potential solution to the rapid, precise and consistent identification of the TSJ when performing a retrosigmoid craniotomy. We present our early experience and discuss nuances in the designing, production, and intraoperative phases to optimise the precision of this guide. We suggest two methods to avoid sinus injury in elderly patients: either to plan the craniotomy to the edge of the sinus, or to plan sinus exposure but to use burr drills rather than the osteotome, as in our case, to expose the sinus.

Humans↗

PubMed2026

Effectiveness of passive vs. assistive robotic gait training on functional recovery and neuroplasticity post-stroke: A randomized controlled trial.

OBJECTIVE: This study seeks to compare the impacts of various robotic gait training (RAGT) modes on lower limb motor function recovery in stroke patients while exploring the corresponding neural mechanisms. DESIGN: A single-blind, randomized controlled trial. SETTING: Inpatient Rehabilitation Facility. PARTICIPANTS: Forty-eight patients aged 18-80 who had experienced their first unilateral subacute stroke accompanied by walking impairments were included. INTERVENTIONS: Participants were randomly assigned to: (1) assistive mode training, (2) passive mode training, or (3) control group receiving only traditional rehabilitation. Clinical and neurological outcomes were assessed at pre-intervention (T0), and post-2-week intervention (T1). MAIN OUTCOME MEASURES: Outcomes were evaluated using the Fugl-Meyer Assessment for Lower Extremity, Berg Balance Scale, Modified Barthel Index, the Functional Ambulatory Category, and functional near-infrared spectroscopy. RESULTS: Among the 48 patients recruited, significant time effects were observed across all groups in FMA-LE scores (p < 0.001). Notable improvements were detected in the conventional group (MD = 2.69, p＜0.01) and the passive group (MD = 3.67, p < 0.001), with the assistive mode also demonstrating a significant effect (MD = 1.79, p < 0.05). BBS scores improved across all groups; however, no significant differences were noted between the groups (p = 0.11). Similarly, MBI scores showed a significant time effect (p < 0.001), without notable group differences (p = 0.29). CONCLUSION: All training modalities effectively enhanced motor function, balance, and daily living skills in stroke patients. Distinct cortical activation and connectivity patterns were observed between training modalities, which may reflect different neuroplastic mechanisms. These preliminary neural differences may help inform personalized rehabilitation strategies, although no clinical superiority of one mode over another can be concluded from the present data.

Humans↗

PubMed2026

Pembrolizumab-Chemotherapy Versus Pembrolizumab in Head and Neck Squamous Cell Carcinoma: A PD-L1 CPS-Stratified Analysis of Updated KEYNOTE-048 Data.

Based on KEYNOTE-048, pembrolizumab monotherapy and pembrolizumab-chemotherapy are established category 1 first-line treatments for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) with programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥ 1. We compared their efficacy using updated trial data. We analyzed 4-year progression-free survival on next-line therapy (PFS2) and 5-year overall survival (OS) data from KEYNOTE-048 by reconstructing time-to-event data using KMSubtraction. Efficacy was compared in CPS 1-19 and CPS ≥ 20 subgroups using Kaplan-Meier estimates, Cox models, restricted mean survival time (RMST), and landmark analyses. Among 499 patients with CPS ≥ 1, 240 (48.1%) had CPS 1-19 and 259 (51.9%) had CPS ≥ 20. In the CPS 1-19 subgroup, pembrolizumab-chemotherapy showed numerically longer median PFS2 (10.1 vs. 8.0 months; hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.62-1.06) and OS (12.8 vs. 10.8 months; HR: 0.87; 95% CI: 0.67-1.15) versus monotherapy, without statistical significance. For CPS ≥ 20 patients, efficacy was comparable between regimens, with similar median PFS2 (11.3 vs. 11.7 months; HR: 0.95) and OS (14.7 vs. 14.9 months; HR: 0.96). RMST and landmark analyses showed an early PFS2 benefit and a trend toward OS benefit with pembrolizumab-chemotherapy in CPS 1-19, with comparable outcomes in CPS ≥ 20. Pembrolizumab-chemotherapy showed a trend toward improved outcomes in the CPS 1-19 subgroup, with comparable efficacy in the CPS ≥ 20 subgroup, supporting a refined first-line strategy: monotherapy for CPS ≥ 20 to minimize toxicity, and combination therapy for CPS 1-19 to potentially enhance disease control.

Humans↗

PubMed2026

Dual-Reporter Gene-Based Multimodal Imaging for Tracking Mesenchymal Stem Cells in Diabetic Skin Wound Repair.

BACKGROUND: Diabetic foot ulcer (DFU) is a clinically challenging complication characterized by poor healing outcomes, and conventional therapies provide limited benefit. Mesenchymal stem cell (MSC) transplantation offers a promising strategy for DFU repair. However, the low survival of transplanted MSCs in the hostile wound microenvironment, coupled with the lack of real-time, non-invasive methods to track these cells in vivo, severely hampers their therapeutic efficacy and clinical translation. METHODS: We engineered MSCs to co-express a dual reporter system comprising near-infrared fluorescent protein (iRFP) and ferritin heavy chain (FTH1). These modified cells were then integrated with a fibrin glue (FG) scaffold to create a unified platform that supports both multimodal imaging and therapeutic function within skin wounds. First, FTH1 overexpression enhances the antioxidant capacity of MSCs, while the FG scaffold provides structural support; this combination enhances cell survival and retention. Second, the iRFP/FTH1 dual reporter enables near-infrared fluorescence imaging and MRI-based localization, establishing a multimodal platform for real-time cell tracking. RESULTS: In a full-thickness skin defect model in diabetic mice, multimodal imaging revealed that transplanted cells persisted in the wound area for approximately seven days. Treatment with iRFP/FTH1-MSCs/FG significantly accelerated wound closure and promoted hair follicle regeneration and angiogenesis. Additionally, local iron deposition resulting from FTH1 expression enhanced fibroblast migration and collagen synthesis, further facilitating extracellular matrix remodeling. Mechanistic studies demonstrated that this therapy drives macrophage polarization toward the anti-inflammatory M2 phenotype and activates the PI3K-AKT-VEGF signaling pathway. These complementary effects synergistically enhance tissue regeneration and systematically improve diabetic wound healing. CONCLUSIONS: Collectively, this multimodal stem cell-scaffold system effectively integrates dynamic cell tracking with stem cell therapy during skin wound repair. It addresses a critical technical gap in visualizing stem cells within the wound microenvironment and provides valuable methodological and theoretical foundations for optimizing regenerative strategies for diabetic skin wounds.

Animals↗

PubMed2026

Patient-reported outcomes with tarlatamab in extensive-stage small cell lung cancer after platinum-based chemotherapy: results from the phase 3 DeLLphi-304 trial.

BACKGROUND: Extensive-stage small cell lung cancer (ES-SCLC) is associated with a high symptom burden and impaired health-related quality of life (HRQoL). This prespecified analysis from the phase 3 DeLLphi-304 trial evaluated patient-reported outcomes (PROs) for tarlatamab versus standard-of-care (SoC) chemotherapy following first-line platinum-based therapy. METHODS: DeLLphi-304 is a multicenter, open-label, randomized phase 3 study in adults with ES-SCLC. PROs were assessed using validated instruments, including the EORTC QLQ-C30, EORTC QLQ-LC13, FACT-G GP5, BPI-SF, and the EQ-5D-5L visual analogue scale. Change from baseline, response rates, and time to deterioration in these PROs were analyzed. RESULTS: PRO data from all 509 patients enrolled were evaluated. Compliance with QLQ-C30 and QLQ-LC13 assessments remained above 69% through 19 weeks. A higher proportion of patients receiving tarlatamab achieved symptom or functional improvement at 19 weeks compared with SoC in chest pain (19% vs 10%), cough (35% vs 26%), dyspnea (22% vs 7%), physical functioning (13% vs 8%), and global health status (23% vs 15%), respectively. Tarlatamab also delayed deterioration in symptoms, physical functioning, and pain at worst relative to SoC. FACT-G GP5 results indicated that patients receiving tarlatamab were less bothered by treatment side effects over time. CONCLUSIONS: In addition to its previously reported antitumor activity, tarlatamab demonstrated clinically meaningful improvements in symptoms and HRQoL compared with SoC. These findings support a favorable benefit-risk profile of tarlatamab in patients previously treated for ES-SCLC.

Humans↗

PubMed2026

Ablative radiotherapy in castration-resistant prostate cancer.

OBJECTIVE: To prove the oncological benefit of ablative radiotherapy in patients with up to five metastases from castration-resistant prostate cancer (CRPC) a single-centre randomised trial was initiated. PATIENTS AND METHODS: This monocentric, randomised, phase II clinical trial enrolled patients with up to five prostate-specific membrane antigen-positive bone or lymph node metastases developing prostate-specific antigen (PSA) progression during androgen deprivation (ADT) or ADT and androgen-receptor targeted therapy. Participants were randomised (2:1) to receive metastasis-directed therapy (MDT) or observation (OBS) without changing systemic therapy. The primary endpoint was the proportion of patients having PSA progression within 1 year, with statistical analyses conducted using intention-to-treat principles. Here, results of a planned interim analysis of the primary endpoint are reported. RESULTS: A total of 30 patients (12 in the observation arm and 18 in the MDT arm) were enrolled, PSA progression within 1 year occurred in 44% of the MDT group vs 75% in the OBS group (P = 0.14, not significant). The median time to PSA progression was significantly longer in the MDT arm (12.4 months) compared to the OBS arm (2.9 months, P = 0.03). The pre-defined criteria to discontinue the study were not met. Limitations include the single-centre design and small sample size at interim analysis. CONCLUSION: This pre-planned interim analysis of the primary endpoint did not meet the discontinuation criteria of the study protocol, suggesting that MDT in oligometastatic CRPC may extend the time to PSA progression without immediate change of systemic therapy. The continuation of the study in a multicentre setting is planned (Institutional funding by the TU Dresden, ClinicalTrials.gov identifier: NCT04141709).

Humans↗

PubMed2026

The impact of prehabilitation on postoperative outcomes in patients undergoing radical prostatectomy for prostate cancer: a systematic review and meta-analysis.

PURPOSE: Preoperative rehabilitation training can optimize functional reserve before radical prostatectomy (RP), thereby improving postoperative outcomes. However, its effects on urinary incontinence, erectile function, and quality of life (QoL) remain controversial. This study systematically evaluated these outcome measures. METHODS: Data from randomized controlled trials (RCTs) were retrieved from the PubMed, Cochrane Library, Embase, and CINAHL databases. The risk of bias was assessed using the RoB-2 tool, and meta-analysis was performed using Stata 18.0 software. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment. Meta-analyses were conducted using fixed- or random-effects models according to heterogeneity. Outcomes included urinary incontinence incidence, urinary incontinence severity, erectile function, and QoL at different postoperative follow-up time points. RESULTS: 16 randomized controlled trials involving 1,542 participants were included. Prehabilitation significantly reduced the incidence of urinary incontinence at 1 month (OR = 0.58, 95% CI 0.39-0.84) and 6 months (OR = 0.52, 95% CI 0.28-0.96) after RP, with a non-significant borderline reduction at 3 months, and no significant benefit at 12 months. No significant improvement was observed in urinary incontinence severity or erectile function at any follow-up time point. Prehabilitation significantly improved QoL within 3 months (SMD = -0.70, 95% CI -1.08 to -0.32) and 6 months (SMD = -0.45, 95% CI -0.74 to -0.16) postoperatively. However, within 12 months, the effect size attenuated, showing only a marginal trend that did not reach statistical significance (SMD = -0.33, 95% CI -0.66 to 0.00). Risk of bias was generally moderate. CONCLUSION: Prehabilitation reduces early incontinence and improves QoL post-RP, but its effects on severity and erectile function remain unclear. SYSTEMATIC REVIEW REGISTRATION: PROSPERO [CRD420251183407].

Humans↗

PubMed2026

Short-term aerobic exercise as an adjunct treatment for depression in acute geriatric psychiatry: Results of a randomized controlled trial.

BACKGROUND: This randomized controlled trial examined whether short-term aerobic exercise provided additional clinical benefit over an active control in older inpatients with depression in geriatric psychiatry. METHODS: 100 patients (mean age 76 years) were randomized to 2-week supervised aerobic ergometer training (intervention group, IG) or a flexibility program (control group, CG), both delivered in addition to treatment as usual (TAU). Adherence, training exposure and adverse events were recorded to assess feasibility. The primary outcome was clinical improvement measured with the Clinical Global Impression of Change (CGI). Secondary outcomes included depressive symptom severity assessed by the Beck Depression Inventory-II (BDI-II) and clinician-rated Hamilton Rating Scale for Depression (HAMD), physical activity, 6-min walk test (6MWT) performance, and fluoxetine-equivalent antidepressant dose (FLX). RESULTS: Thirty-nine participants attended at least 80% of sessions, with lower adherence in the IG. Weekly training duration differed between groups (74.0 ± 31.9 vs. 95.0 ± 25.3 min/week, p = .003). CGI did not differ between groups (IG: MD -0.31, 95% CI -0.67 to 0.05; p = .069). Depressive symptom severity decreased over time in both groups (p < .001), without significant between-group differences for HAMD (MD -0.22, 95% CI -2.55 to 2.12) or BDI-II (MD -0.62, 95% CI -3.68 to 2.45). 6MWT and FLX increased over time (both p < .001), without group differences (6MWT: MD -1.08 m, 95% CI -20.04 to 17.89; FLX: MD 5.69 mg/day, 95% CI -2.40 to 13.77). CONCLUSION: Short-term aerobic exercise was deliverable, but showed no additional clinical benefit over low-intensity flexibility during TAU. Further research should determine dose, duration and adherence for clinically relevant effects.

Humans↗

PubMed2026

Effect of Food on Balcinrenone/Dapagliflozin Pharmacokinetics and the Pharmacokinetics of Balcinrenone When Dosed with a P-gp Inhibitor.

Balcinrenone (AZD9977) is a novel selective non-steroidal mineralocorticoid receptor antagonist with a distinct mode of action being developed as a fixed-dose combination with the sodium-glucose cotransporter-2 inhibitor dapagliflozin for the treatment of heart failure with impaired kidney function, and chronic kidney disease. In this Phase 1 randomized open-label three-way crossover study we investigated the effect of food on balcinrenone/dapagliflozin pharmacokinetics, and the pharmacokinetics of balcinrenone when dosed with a P-glycoprotein (P-gp) inhibitor. Fourteen healthy participants were administered an oral capsule of balcinrenone/dapagliflozin 40 mg/10 mg in three dosing periods: fasted (reference), fed (high-fat, high-calorie meal) and with a P-gp inhibitor (quinidine 300 mg × 2). Balcinrenone exposure was comparable in the fed and fasted states (geometric mean ratios [GMRs] [90% CI]: maximum plasma concentration [Cmax] 1.05 [0.88, 1.25]; area under the plasma concentration-time curve from time 0 to infinity [AUCinf] 1.12 [1.06, 1.19]). In the fed state, dapagliflozin AUCinf was comparable to the fasted state (GMR [90% CI] 1.05 [1.01, 1.09]), whereas Cmax was decreased (GMR [90% CI] 0.59 [0.51, 0.69]), in line with previous dapagliflozin food interaction studies. Co-administration with quinidine increased balcinrenone exposure: GMRs (90% CI) 1.48 (1.24, 1.76) and 1.24 (1.17, 1.31) for Cmax and AUCinf, respectively, but AUC fold increase was <2, the level used for classification of sensitive P-gp substrates. All interventions were well tolerated. In conclusion, this study supports dosing of balcinrenone/dapagliflozin without regard to food. Balcinrenone is not considered a sensitive P-gp substrate. No P-gp based dosing precautions are warranted based on this study.

Adult↗

PubMed2026

Prevalence and pattern of psychological symptoms in form of dental fear and anxiety in children and adolescents with traumatic dental injuries: a systematic review.

BACKGROUND/AIMS: This systematic review aimed to evaluate the level and pattern of dental fear and anxiety (DFA) amongst children and adolescents with traumatic dental injuries (TDI) and, where available, to compare these outcomes with non-traumatised controls. METHODS: An a priori protocol was developed and registered in PROSPERO (CRD420261329946). A comprehensive literature search was conducted in PubMed, EMBASE, Web of Science, and Scopus on 3 March 2026, with additional grey literature, citation, and reference searching. No language or time restrictions were applied. Observational clinical studies assessing DFA in individuals with TDI using validated tools were included. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Joanna Briggs Institute checklist. Certainty of evidence was evaluated using the GRADE approach. RESULTS: A total of 2885 records were identified, of which 4 cross-sectional studies met the inclusion criteria after screening. Studies were conducted in Croatia and Kosovo and included paediatric populations. Sample sizes ranged from 147 to 505 participants. Different validated scales (CFSS-DS, CDAS, S-DAI) were used to assess DFA. Overall, children with TDI demonstrated predominantly low levels of dental fear and anxiety across assessment tools. However, findings were inconsistent, with some studies reporting lower or similar anxiety levels in TDI patients compared to controls. Risk of bias was moderate or high in three of the four studies, and the overall certainty of evidence was rated as low to very low due to methodological limitations, heterogeneity, and imprecision. CONCLUSION: The limited available evidence suggests that children and adolescents with TDI do not consistently present with higher levels of dental fear and anxiety than non-traumatised controls. These findings indicate that TDI does not inherently cause DFA, underscoring the critical role of empathetic behaviour support in mitigating post-traumatic dental fear. However, the evidence is based on a small number of regionally concentrated cross-sectional studies with low to very low certainty. Future prospective studies using standardised TDI classifications, validated DFA instruments, and clearly defined assessment time points are needed.

Dental anxiety↗

PubMed2026

Effect of adding umbilical cord blood derived stem cells to haploidentical stem cell transplant (haplo-cord) on post-transplant survival and graft-versus-host disease in patients with hematological malignancies: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Haploidentical stem cell transplantation (haplo-SCT) carries a substantial risk of graft-versus-host disease (GvHD), whereas umbilical cord blood (UCB) transplantation offers lower GvHD risk but slower engraftment. The haplo-cord approach combines both graft sources, aiming to mitigate GvHD while ensuring timely engraftment. This meta-analysis compares haplo-cord transplantation with haplo-SCT alone for the treatment of hematological malignancies. METHODS: Four electronic databases and two clinical trial registries were systematically searched. Effect sizes from eligible studies were pooled using odds ratios (ORs) for dichotomous outcomes and hazard ratios (HRs) for time-to-event outcomes. RESULTS: Twelve studies met the inclusion criteria. Haplo-cord was associated with a statistically significant reduction in chronic GvHD (OR = 0.62, 95%-CI: 0.42-0.93), while no significant difference was observed for grade II-IV acute GvHD (OR = 0.75, 95%-CI: 0.52-1.09). Survival outcomes favored haplo-cord, with lower HRs for overall survival (HR = 0.68, 95%-CI: 0.53-0.86) and event-free survival (HR = 0.61, 95%-CI: 0.52-0.72), while non-relapse mortality was not significant. Relapse at 3 years was significantly lower with haplo-cord (OR = 0.54, 95%-CI: 0.35-0.82). Haplo-cord also demonstrated higher day-30 engraftment, along with lower relapse-related and GvHD-related mortality, while CMV and EBV viremia showed no difference between groups. CD34 selection in the haplo graft significantly influenced effect sizes and heterogeneity in both subgroup analyses and meta-regression for acute GvHD. CONCLUSION: Haplo-cord transplantation improves GvHD outcomes, survival, and relapse risk compared with haplo-SCT alone. However, whether protocol optimization, possibly via CD34 selection, confers additional benefit remains uncertain and requires confirmation in future studies.

Humans↗

PubMed2026

Effects of antidepressant administration on physical performance and perceived exertion in athletes: systematic review and meta-analysis.

INTRODUCTION: Antidepressants are commonly prescribed in athletes with depressive disorders, yet their potential effects on physical performance and perceived exertion remain unclear, and existing evidence is limited and inconsistent. AIM: This systematic review and meta-analysis aimed to evaluate the effects of antidepressant use on objective physical performance and perceived exertion in athletes. METHOD: A systematic literature search was conducted in PubMed, the Cochrane Library, Web of Science, and SPORTDiscus through March 2025. Eligible studies were randomised controlled trials (RCTs) published in English that enrolled elite, competitive, or recreational athletes; compared antidepressant administration with placebo or no treatment; and reported at least one objective or subjective performance-related outcome. Meta-analyses were performed using random-effects models, and pooled mean differences with 95% confidence intervals (CI) were calculated. This systematic review and meta-analysis was registered in PROSPERO (CRD420251123740). RESULTS: Ten crossover RCTs involving 99 male athletes were included. Interventions included a norepinephrine reuptake inhibitor (reboxetine), a norepinephrine-dopamine reuptake inhibitor (bupropion), and selective serotonin reuptake inhibitors (fluoxetine or paroxetine). Acute antidepressant administration was associated with a small increase in rating of perceived exertion (RPE; mean difference 0.52 points on the Borg 6-20 scale, 95% CI 0.01-1.04; p < 0.05). No significant overall effects were observed for time-trial performance, mean power output, heart rate or blood lactate. However, subgroup analyses showed that reboxetine significantly impaired time-trial performance (mean difference 3.62 min, 95% CI 0.18-7.06; p < 0.05) and reduced mean power output (mean difference - 19.97 W, 95% CI - 36.87 to - 3.06; p < 0.05). CONCLUSION: Short-term antidepressant administration in athletes was associated with a small increase in perceived exertion, without consistent impairment in objective physical performance. As the current evidence derives exclusively from male athletes and acute exposure, further research should clarify its relevance to female athletes and to longer-term antidepressant treatment in athletes with depressive disorders.

Humans↗

PubMed2026

Effects of a situational interest-based rotational fitness training program on positive affect in university students: A randomized controlled trial.

BACKGROUND: To evaluate whether a 12-week situational interest-based rotational fitness program improved positive emotional states in university students, to compare module-specific effects, and to examine whether the intervention moderated the heart rate-emotion association. METHODS: In this 2-arm randomized controlled trial, 560 freshmen from 10 Chinese universities were assigned to an experimental (n = 280) or control group (n = 280). The experimental group completed weekly 90-minute sessions covering strength, endurance, speed, and agility modules; controls received regular physical education. Positive emotional states were assessed using the positive well-being subscale of the Subjective Exercise Experiences Scale through ecological momentary assessment at 3 points per session, yielding over 14,000 observations. Linear mixed-effects models tested group, time, group × time, heart rate, and heart rate × group effects. Assessors and analysts were blinded. Ethical approval for the trial was granted by the Institutional Review Board of Capital University of Physical Education and Sports (2025A055). RESULTS: Improvement was greater in the experimental group than in controls (EMM change: 1.843 vs 0.505; difference = 1.338, 95% confidence interval [CI]: 1.275-1.400, P < .001). At week 12, the raw between-group difference was 1.85 (d = 2.23), and all group × week interactions from weeks 2 to 12 were significant. Heart rate positively predicted emotional states in controls (B = 0.005, 95% CI: 0.003-0.007), but this association was attenuated in the experimental group (interaction B = -0.008, 95% CI: -0.011 to -0.005). Strength and agility showed significant improvements, while endurance produced consistently higher emotional states across assessment points. Heart rate moderation was significant for strength and endurance, but not speed or agility. CONCLUSION: The rotational program improved positive emotional states more than regular physical education, although effects varied by module. Strength showed the most robust benefit. The program also weakened, but did not eliminate, the heart rate-emotion association during more demanding activities.

Humans↗

PubMed2026

Optimising Exercise Prescription: A Meta-Analysis Examining the Dose Response of Exercise Duration on Cardiorespiratory Fitness Following HIIT and MICT.

BACKGROUND: High-intensity interval training (HIIT) is often promoted as a time-efficient alternative to moderate-intensity continuous training (MICT) for improving cardiorespiratory fitness, yet the duration of HIIT sessions varies considerably across studies. OBJECTIVE: We aimed to characterise the dose-response relationship between exercise session duration and the improvement in cardiorespiratory fitness for HIIT and MICT. METHODS: A dose-response meta-analysis of randomised controlled trials comparing exercise duration in HIIT and MICT, following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and registered in PROSPERO (CRD42022335590). Effect sizes were calculated using a random-effects meta-analysis. The primary outcome was maximal oxygen uptake (VO2max). Secondary outcomes included blood pressure, lipid profiles, glucose metabolism markers and body composition measures. A one-stage random-effects dose-response meta-analysis was performed to examine the relationship between exercise duration and adaptations. We searched PubMed and Google Scholar; eligibility criteria for selecting studies were randomised controlled trials in humans, published in English and exercise interventions lasting at least 4 weeks. RESULTS: We identified 69 randomised controlled trials (2387 participants). High-intensity interval training elicited greater improvements in VO2max than MICT (d = 0.38, 95% confidence interval 0.27-0.49, p < 0.001). High-intensity interval training demonstrated a non-linear dose-response relationship between exercise session duration and VO2max, with 80% of maximal effect (changes in VO2max = 3.45 mL/kg/min) achieved with only ~11 min/session (95% confidence interval 9.5-40.2). Moderate-intensity interval training showed a linear dose-response relationship between exercise session duration and VO2max, requiring ~52 min/session to achieve 80% of the maximal observed effect (95% confidence interval 30.4-55.8). The dose-response relationship was consistent across populations. High-intensity interval training and MICT had comparable effects in improving cardiometabolic risk factors. CONCLUSIONS: High-intensity interval training demonstrated a non-linear dose response, with 80% of maximal effect on VO2max in ~11 min/session, whilst MICT required four to five times longer to reach similar responses. The different types of training had comparable effects on cardiometabolic risk factors.

Journal Article↗

PubMed2026

Effects of Transcranial Direct Current Stimulation and Individualized Physical Therapy on Pain and Function in Individuals With Chronic Knee Pain: A Pilot Study.

BACKGROUND AND PURPOSE: Noninvasive brain stimulation is a promising neuromodulatory intervention for chronic pain. This study aimed to determine the impact that transcranial direct current stimulation (tDCS) in combination with individualized physical therapy (PT) has on pain and function in individuals with chronic knee pain. METHODS: This study was a preliminary pragmatic, triple-blinded, randomized, and sham-controlled clinical trial performed in an outpatient orthopedic physical therapy clinic. Participants participated in 5 sessions of active or sham tDCS followed by individualized PT intervention. Pain outcomes included the Numeric Pain Rating Scale, Movement-Evoked Pain, pressure pain thresholds (PPT), and the Central Sensitization Inventory. Functional outcomes included the 2-minute walk test, 5-time sit-to-stand test, quadriceps strength, knee range of motion, Patient Specific Functional Scale, and the Lower Extremity Functional Scale. RESULTS: Thirty participants with chronic knee pain completed the study. There were no significant differences observed for primary patient-centered pain and functional outcomes. For secondary outcomes, the active tDCS group had a significant effect (p < 0.05) on percent change in lateral joint line PPT and a significant multivariate effect of group on PPT change scores for 3-site and 5-site clusters (p < 0.05). Exploratory responder analyses demonstrated that the active tDCS group was 12.8 times more likely to achieve the minimum detectable change in quadriceps strength improvement compared with the sham tDCS group (p < 0.05). DISCUSSION: There were no significant between-group differences for primary pain and functional outcomes. However, the active tDCS group showed improvements in pain sensitivity, as measured by PPT, and quadriceps strength, which were superior to those seen in the sham tDCS group. These preliminary findings provide insight into possible mechanisms of tDCS in addressing pain as opposed to efficacy. Given that there were no clear between-group differences in patient-centered outcomes, there is insufficient evidence for routine tDCS use for chronic knee pain. TRIAL REGISTRATION: NCT06132412.

Humans↗

PubMed2026

Comfort and Usability of Digital Versus Conventional Custom-Fit Mouthguards: A Randomized Clinical Trial.

BACKGROUND/OBJECTIVES: The use of mouthguards protects teeth and the supporting tissues against impacts. Digital impressions and 3D-printed models can reduce manufacturing steps and minimize discomfort. This study evaluated the fit, comfort, and usability of custom-made mouthguards, obtained by conventional and digital workflow, in amateur athletes. MATERIALS AND METHODS: Amateur athletes were recruited for this randomized, double-blind, crossover clinical study. Each participant received two 4-mm-thick custom-fit mouthguards made of ethylene vinyl acetate (EVA) sheets using two protocols: conventional impression using alginate to produce dental stone cast (CMP) and intraoral digital scanning to produce 3D-printed resin models (DMP). Each mouthguard was worn during all training and matches over 3 months. The order of mouthguard use was randomly assigned. Patient satisfaction with the impression protocol and mouthguard use, model accuracy, and mouthguard fit were assessed. RESULTS: Overall, 46 participants completed the study. The DMP protocol required less execution time (p = 0.023), caused less discomfort (p = 0.018), anxiety (p = 0.008), nausea (p = 0.027), difficulty breathing (p < 0.001), and unpleasant taste (p = 0.006) compared to the CMP protocol. The pain (p = 0.971) perceived by the participants was similar in both impression protocols. The CMP-mouthguards were considered to be better fitting by the majority of participants (p = 0.027). Between-group comparisons revealed that DMP-mouthguard caused less discomfort immediately postadaptation (p = 0.034), with no significant differences observed at 30 or 90 days. CONCLUSIONS: The digital workflow demonstrated to be efficient in the fabrication of mouthguards. Digital impression was more comfortable, requiring less execution time, with more accurate printed models and produced mouthguards with reported comfort and fit levels similar to those manufactured conventionally.

Humans↗

PubMed2026

Preoperative intramuscular testosterone and urethrocutaneous fistula formation after primary hypospadias repair.

INTRODUCTION: Preoperative androgen stimulation is widely used before hypospadias repair to increase penile dimensions and optimise surgical conditions. However, its impact on postoperative complications, particularly urethrocutaneous fistula formation, remains controversial. OBJECTIVE: To evaluate the association between preoperative intramuscular testosterone therapy and urethrocutaneous fistula formation in children undergoing primary hypospadias repair. STUDY DESIGN: This was a retrospective comparative analysis of prospectively collected clinical data from 111 boys undergoing primary hypospadias repair at a single tertiary pediatric urology center. Patients were divided into two groups: those who did not receive hormonal therapy (Group 1, n = 55) and those who received intramuscular testosterone enanthate (2 mg/kg administered 5 and 2 weeks before surgery; Group 2, n = 56). Preoperative penile measurements, operative characteristics, and postoperative complications were compared. The primary outcome was urethrocutaneous fistula formation. The mean follow-up duration was 11.9 months (median 7 months). RESULTS: Preoperative testosterone therapy was associated with significant increases in glans diameter and stretched penile length at the time of surgery. The hormone-treated group had a significantly higher proportion of proximal hypospadias (p = 0.001), underwent more complex urethroplasty procedures, and had longer operative times (p = 0.007). Postoperative edema and local inflammatory changes were more frequently observed in the hormone-treated group. Despite these differences, urethrocutaneous fistula occurred in four patients in each group (7.3% vs 7.1%, p = 0.357), with no statistically significant difference between groups. DISCUSSION: Despite greater baseline anatomical severity and operative complexity in the hormone-treated group, preoperative testosterone administration was not associated with an increased risk of urethrocutaneous fistula. These findings suggest that improved tissue bulk and vascularity may offset the potential adverse effects of transient inflammatory changes. CONCLUSION: Selective preoperative intramuscular testosterone therapy was not associated with increased urethrocutaneous fistula risk and may be considered a reasonable adjunct in appropriately selected patients undergoing primary hypospadias repair. CLINICAL/TRANSLATIONAL APPLICABILITY: These findings provide clinical reassurance that preoperative testosterone can be used selectively in patients with smaller penile dimensions or anticipated technical difficulty without increasing fistula risk, thereby supporting shared decision-making in clinical practice.

Humans↗