The high placebo response in acne clinical trials has slowed down the progress of new drug development. Therefore, this study used a model-based meta-analysis method to quantitatively analyse the placebo response and explore its influencing factors. This study included 21 627 subjects from acne-related randomized double-blind placebo-controlled trials. Pharmacodynamic models were developed for four endpoints: total lesion counts absolute change, noninflammatory lesion counts absolute change, inflammatory lesion counts absolute change and treatment success rate defined by the investigator global assessment scale. Covariate modelling and subgroup analyses were performed to explore influencing factors. Placebo response under different conditions was simulated based on the final model. Model simulation results showed that for the typical population, after 12 weeks of placebo intervention, their total lesion counts, noninflammatory lesion counts and inflammatory lesion counts were reduced by 19.05 (95% confidence interval: 16.54-21.52), 10.71 (9.18-12.17) and 8.58 (7.55-9.58) from baseline, respectively; the treatment success rate was 11.83% (9.41%-14.35%). Baseline lesion counts, female proportion, Caucasians proportion, sample size, dosage form, type of control drug, skincare programme, number of centres, funding source, study locations and publication year could all influence placebo response. We also used our model to synthesize placebo arms for two single-arm studies, demonstrating the efficacy superiority of the drugs. This study quantitatively described the time-response relationship of placebo in acne clinical trials, revealing the influence of baseline characteristics and trial design characteristics, which could provide evidence for optimizing clinical trial design. PROSPERO (CRD420250649902).

Optimal perampanel dose as the treatment for refractory partial-onset seizures: Network meta-analysis based on pivotal randomized double-blind clinical trials.

Effective postoperative pain management is challenging because of adverse effects associated with traditional analgesic methods. Multimodal analgesia, targeting multiple pain pathways, offers improved pain relief while reducing side effects. The authors evaluated the analgesic and anti-inflammatory effects of the ReproGel drug delivery system (DDS) combined with ropivacaine in a rat model of postoperative pain. Sixty-four Sprague-Dawley rats were randomly assigned to four groups: sham treatment, ReproGel DDS, ropivacaine 0.375%, and ReproGel DDS + ropivacaine 0.375%. Mechanical withdrawal threshold (MWT) tests and rotarod assessments were conducted at baseline; at 30, 60, 90, 120, 180, and 240 minutes; at 24 and 48 hours; and at 1 week postoperatively. Blood samples were collected at 24, 48 hours, and 1 week to measure levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 before euthanasia. The ReproGel DDS + ropivacaine group demonstrated significantly higher MWT values, demonstrating enhanced analgesia from 30 to 240 minutes postoperatively. Combination treatment with ReproGel demonstrated superior effectiveness at 240 minutes, outperforming ropivacaine alone, indicating a sustained analgesic effect. IL-1β and IL-6 levels were significantly reduced in groups receiving ropivacaine, particularly in the ReproGel DDS + ropivacaine group, at 24 and 48 hours postoperatively. No motor impairment was observed, confirming the safety of ReproGel DDS + ropivacaine in preserving motor function. The combination of ReproGel DDS and ropivacaine 0.375% in a postoperative rat model offers prolonged analgesic and anti-inflammatory effects without motor impairment, positioning it as a safe and effective option for postoperative pain management.

To evaluate the efficacy of nonablative capacitive-resistive monopolar radiofrequency on sexual function and vaginal health in postmenopausal women with genitourinary syndrome of menopause. This was a single-blind, randomized, controlled clinical trial. The participants were randomly assigned to receive six weekly sessions of capacitive-resistive monopolar radiofrequency (n=32) or sham treatment (n=30). Sexual function was assessed using the Female Sexual Function Index (FSFI) and vaginal health was assessed using the Vaginal Health Index (VHI). The estrogenic status was determined by vaginal cytology, which involves calculating the proportions of basal, intermediate, and superficial cells. Assessments were conducted at baseline, post-treatment, and 12-week follow-up. Compared with the control group, the intervention group showed significantly greater improvements in the Female Sexual Function Index and Vaginal Health Index at post-treatment and at the 12-week follow-up. FSFI mean changes were 5.86 versus 1.33 at posttreatment ( P <0.001) and 4.41 versus -0.41 at 12-week follow-up ( P =0.011). VHI mean changes were 4.75 versus -0.03 at post-treatment ( P <0.001) and 6.90 versus -0.66 at follow-up ( P <0.001). The effect sizes were moderate to large for the FSFI (Cohen's d >0.77, 95% CI, 0.25-1.29) and large for the VHI ( d >3.49, 95% CI, 2.68-4.28). No significant changes were observed in estrogenic status, and no adverse events were reported. Capacitive-resistive monopolar radiofrequency significantly improved sexual function and vaginal health in women with genitourinary syndrome of menopause, thereby supporting its use as a safe, nonhormone treatment option.

Effectiveness of diathermy in reducing subcutaneous adipose tissue affected by lipedema: a pilot study.

Differential effects of transcranial direct current stimulation on depression symptom clusters.

TRANSFORM-1 Phase 3 study: Efficacy and safety of navitoclax plus ruxolitinib in patients with untreated myelofibrosis.

Response letter to the editor: efficacy of cervical physical therapy on pain sensitivity in patients with migraine compared to no treatment, sham treatment or usual medical care: a systematic review and meta-analysis

Inferior alveolar nerve (IAN) sensory disturbance after mandibular third molar extraction can persist and affect speech, mastication, and quality of life. Photobiomodulation (PBM) has been used to promote peripheral nerve recovery, but the most suitable irradiation strategy remains unclear. Laser acupuncture (LA) delivers PBM to predefined acupoints and may provide both local and central neuromodulatory effects. To compare standardized LA with direct nerve-trajectory PBM for post-extraction IAN hypoesthesia in a randomized, double-blind, sham-controlled trial. Adults aged 18-60 years with unilateral IAN hypoesthesia lasting ≥7 days and ≤12 weeks were randomized (1:1:1) to LA, direct PBM along the external IAN projection, or sham treatment. All participants received mecobalamin (0.5 mg, three times daily) for 30 days. PBM was delivered using an 808-nm diode laser (continuous wave, 100 mW; beam area 1.0 cm2), 90 s/site (9 J; 9 J/cm2), every other day for 15 sessions. LA used a fixed 5 + 2 prescription: ST4, ST6, ST7, CV24, Jiachengjiang (EX-HN19), plus LI4 and PC6. Primary outcomes were two-point discrimination (TPD) and Semmes-Weinstein monofilament examination (SWME) at day 30. Secondary outcomes included Visual Analog Scale (VAS) numbness, additional sensory tests, and day-60 follow-up. Sixty participants completed the intervention. Both active groups improved more than sham for TPD and SWME (group × time p < 0.01). Mean TPD change at day 30 was -3.2 ± 1.8 mm (LA) and -2.6 ± 1.7 mm (direct PBM) versus -0.8 ± 1.1 mm (sham). SWME improved by ≥1 grade in 85%, 80%, and 25%, respectively. VAS numbness decreased by 60%, 48%, and 12%, respectively, and the improvement was largely maintained at day 60. No treatment-related adverse events occurred. Under matched PBM dosimetry, both irradiation strategies improved sensory recovery compared with sham. LA produced comparable results and was associated with greater improvement in patient-reported numbness.

This study aimed to assess the clinical and histopathological effects of maximal available and supramaximal energy exposure in direct selective laser trabeculoplasty (DSLT®) on target and nontarget ocular tissues compared with selective laser trabeculoplasty (SLT) and sham treatments. Thirty eyes of 16 Dutch Belted Rabbits were allocated into seven groups: (A) Maximal energy DSLT exposure (2.6 mJ), (B) supramaximal energy DSLT exposure (3.5 mJ) with double nominal density spot spacing, (C and D) nontarget DSLT on sclera and iris at maximal and supramaximal energy, (E) SLT treatment at maximal energy (2.6 mJ), (F) SLT treatment with two overlapping shots at maximal energy (2.6mJ), and (G) sham control. The eyes were examined using a biomicroscope slit lamp, anterior segment OCT (AS-OCT), and a specular microscope at baseline, Day 1, and Weeks 1, 2, and 4 post-treatments. Histopathological evaluation was conducted on eyes enucleated on Days 1 and 29 posttreatment. The study was conducted at the Harlan laboratory, Ness-Ziona, Israel. All DSLT and SLT laser treatments were uneventful. Minor acute responses were observed 1-day posttreatment at the slit lamp biomicroscopy exam, with similar DSLT and SLT responses. No significant clinical or histopathological findings were observed in any treatment groups at 29 days posttreatment. No notable findings indicative of damage to nontarget tissues were noted, including damage to the limbal stem cells. DSLT treatment at the limbus, iris, and sclera yielded no significant clinical or histopathological changes compared to SLT or sham eyes, even with supramaximal energy and double-density exposures.

The Pleurotus ostreatus oyster species is a common edible mushroom, rich in ergothioneine, a bioactive that has previously shown preclinical benefits to cognition when administered in extract form. The OYSCOG study investigated the effects of a 12-week oyster mushroom intervention on cognition, mood, and serum markers in 80 healthy older adults aged 60-80 years. Participants consumed four portions per week of either oyster mushroom (OM) or placebo (PL). All measures were collected at baseline and 12-weeks post-intervention. EEG activity was recorded in a subset of participants (n = 40) at rest and during a simple cognitive task. ANCOVA between baseline and 12-weeks revealed slower task switching reaction times, indicating decreased performance, in the PL group. Increases in negative mood, as indicated by PANAS-X ratings of fear, sadness, and shyness and DASS-21 anxiety ratings, were similarly observed in the PL group. Conversely, DASS-21 anxiety ratings and RAVLT delayed word recall and delayed word recognition were improved for the OM group, while levels of inflammatory markers (cyclo-oxygenase 2 and NADPH oxidase 2) were reduced in an in vitro rodent microglial cell model. After 12-weeks supplementation, the OM group outperformed the PL group in RAVLT delayed word recall and delayed word recognition and displayed lower negative mood, as indicated by PANAS-X sadness, PANAS-X shyness and DASS-21 anxiety. Overall, the 12-week OM intervention, maintained mood and improved episodic memory in older adults compared to PL, alongside reducing markers of inflammation.

Transcranial direct current stimulation (tDCS) has potential as a treatment for adult depression, but its effectiveness in adolescents remains unexplored. This study evaluated the feasibility, safety, and efficacy of tDCS in young in-patients with depression. In a randomized, double-blind, sham-controlled trial, 34 adolescent in-patients (mean age 15.48 years) received ten sessions of either tDCS or sham stimulation over two weeks, alongside standard treatment. Depression severity, quality of life, emotional and behavioral issues, and executive functions were assessed before, immediately after, and two weeks post-treatment. The results indicated that tDCS was feasible and well-tolerated, with 28 patients completing at least eight sessions. Side effects were reported in nearly half of the sessions (45% sham, 48% tDCS), primarily mild to moderate, and no sessions were interrupted due to discomfort. Both groups experienced significant improvements in depressive symptoms and high treatment satisfaction, but no significant differences were found between the tDCS and sham groups. In conclusion, while tDCS appears to be a safe treatment option for adolescents with depression, this study could not show it to be superior to sham treatment. Further research with greater statistical power is needed to control for covariates.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-026-56839-1.

Research on the acute effects of β-alanine supplementation has primarily focused on performance outcomes, with limited attention to the underlying physiological mechanisms. This study aimed to investigate the acute effects of two β-alanine doses on performance, mechanical output, and acid-base balance during a 10 min cycling time trial (10'-TT), and to explore the relationship between buffering-related variables and performance. Eighty-five recreational cyclists performed a 10'-TT under indoor conditions before (control) and following the acute ingestion of β-alanine (moderate-dose β-alanine 10 g-BAM; high-dose β-alanine 20 g-BAH) or placebo (PLA), with each condition tested on separate days. Data were analyzed using two-way repeated-measures ANOVA and correlation analyses. No significant differences were observed in performance variables (distance, speed, cadence, or heart rate; p ≥ 0.751). However, total external mechanical work (kJ) was significantly reduced following acute supplementation (p = 0.028). Notably, the BAM condition reduced the mechanical cost of exercise without impairing performance, and this effect was moderately associated with changes in bicarbonate levels. Acute β-alanine supplementation did not improve performance outcomes but may alter buffering-related physiological responses associated with reduced mechanical work during high-intensity cycling exercise. These findings highlight the relevance of buffering-related mechanisms, particularly bicarbonate dynamics, in modulating the mechanical cost (work performed relative to performance achieved) of high-intensity exercise.

Background/Objectives: Although vitamin K has been implicated in osteoarthritis pathophysiology, the specific effects of vitamin K2 (menaquinone) on cartilage degeneration remain poorly characterized. This study aimed to investigate the effect of oral vitamin K2 supplementation in a monosodium iodoacetate-induced osteoarthritis model. Methods: Twenty-four male Sprague Dawley rats were included in the study and divided into 3 equal groups: sham group, control (osteoarthritis) group, and treatment group. Saline was applied to the right knee of the sham group, and MIA was applied intra-articularly to the right knee of the control and treatment groups to create an osteoarthritis model. Rats in the treatment group were given 8 micrograms (μg)/day of vitamin K2 orally in addition to the standard diet. After 28 days of follow-up, all rats were euthanized. The right knee articular cartilage was examined histologically with Hematoxylin-Eosin and Safranin O and immunohistochemically with type II collagen alpha 1 and Matrix Metalloproteinase-13. Results: Histological evaluation demonstrated significantly lower Mankin scores in the treatment group (4.25 ± 0.83) compared with the control group (11.10 ± 0.83). Immunohistochemical analysis showed more intense type II collagen staining and reduced matrix metalloproteinase-13 staining in the treatment group relative to the control group. Conclusions: Oral vitamin K2 administration was associated with reduced cartilage degeneration and improved matrix preservation at the 28-day endpoint in an induced MIA osteoarthritis rat model.

Large-scale brain network dysfunction is increasingly recognized as an important feature of Alzheimer's disease (AD), offering insight into disease mechanisms and opportunities for targeted therapeutic intervention. The spectral features of this dysfunction remain poorly understood, and how neuromodulatory interventions interact with and reshape these frequency-resolved network signatures has yet to be explored. Triple-transgenic (3×Tg-AD) mice underwent resting-state functional MRI to assess functional connectivity, signal power, and variance across frequency bands after acute and longitudinal transcranial pulse stimulation (TPS), a low-intensity single-pulse neuromodulatory intervention. Novel object recognition testing was used to evaluate exploratory drive and short-term recognition memory following repeated TPS or sham treatment. AD mice exhibited widespread functional connectivity loss accompanied by reduced low-frequency resting-state power and variance, together with a redistribution of spectral energy from slow-5 (0.01-0.027Hz) to slow-4 (0.027-0.073Hz) activity. TPS modulated these abnormalities by increasing low-frequency power, rebalancing slow-5/slow-4 fractional power, and strengthening network coherence, with the most prominent effects in cingulate, insular, piriform, and striatal regions. TPS effects showed a non-linear, region-dependent emergence across stimulation trains, with the strongest and most consistent modulation appearing after repeated stimulation. Similar spectral rebalancing was observed both after acute and longitudinal stimulation, persisting for up to 5 days. In addition, hippocampal regions that showed minimal acute responses exhibited delayed spectral changes at 24h, with further modulation at 120h. TPS-treated 3×Tg-AD mice did not show the decline in object exploration observed in sham-treated animals and showed an exploration-adjusted increase in novel object preference. Frequency-specific neural dynamics are sensitive markers of AD-related dysfunction and may provide a useful framework for tracking disease-related network abnormalities. TPS selectively modulates low-frequency oscillatory activity and network coherence and is accompanied by preliminary behavioral changes, including preserved exploratory engagement and an exploration-adjusted increase in novel object preference in a separate behavioral cohort. This highlights the potential of combining neuromodulation with spectral network analysis to monitor disease-related network dysfunction and treatment-associated responses.

Borderline personality disorder (BPD) is associated with psychosocial dysfunction and has a number of untoward public health associations. There is no established first-line pharmacological treatment for BPD, and available options are not suitable for all individuals. The aim of this study was to evaluate the safety and efficacy of lumateperone in adults with BPD. Sixty adults with BPD were recruited for a randomized, double-blind, placebo-controlled study. Participants received 8-week treatment with lumateperone (42mg/day) or identical placebo in a parallel design. The primary efficacy outcome measure was the clinician-rated Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD). Safety data were collected. Effects of active versus placebo treatment were analyzed using a linear mixed-effects regression model that included terms for treatment group, time, and treatment-by-time interaction. There was no significant interaction between treatment and time on the ZAN-BPD scale at week 8. Lumateperone was generally well tolerated. Secondary measures did not result in statistically significant differences from placebo. Lumateperone did not appear to reduce BPD symptoms compared with placebo. These findings also need to be viewed cautiously given the small sample size, large drop-out rate, and robust placebo response.

ABSTRACT Taurine (TAU) is a conditionally essential amino acid whose consumption has recently increased, particularly among young people, through supplements and energy drinks. It has potential beneficial effects on physical performance; however, scientific evidence remains limited. To evaluate the effects of acute ingestion of 1 g of TAU on metabolic and aerobic capacity in physically active young adults. This experimental, randomized, triple-blind, cross-over study included 16 volunteers (11 women and 5 men). Data were collected during a progressive cardiopulmonary exercise test (CPET) at the Ergoespirometry Laboratory of the Department of Physical Education, Federal University of Pernambuco (DEF-UFPE). After familiarization with the test, participants completed two CPETs, 1 hour after ingesting either TAU or placebo (PLA) capsules, with a 7-day washout period between sessions. A significance level of 5% (p < .05) was adopted for all analyses. No significant differences were observed between the TAU and PLA conditions in the main aerobic capacity variables, including peak oxygen consumption (p = .160), time to exhaustion (p = .361), and respiratory compensation point (p = .166), and in lipid metabolism variables (duration—p = .559 and peak—p = 1.000) and glycolytic metabolism (duration—p = .904 and peak—p = .383). Acute intake of 1 g of TAU did not significantly alter aerobic capacity and energy metabolism in physically active young adults. Future research should consider other dosages and types of activities, different levels of physical fitness, and exercise durations.

Immunoadsorption Versus Sham Treatment for Post-COVID Syndrome: A Randomised Sham-Controlled Crossover Trial

Strategies to augment weight loss, fitness, and body composition are in high demand. The myokine beta-amino-isobutyric acid (BAIBA) has been shown to increase fat loss, while grains of paradise (GOP), a member of the ginger family, may aid weight loss by reducing appetite and increasing thermogenesis.Purpose To evaluate the impact of 56 days of supplementing with L-BAIBA or L-BAIBA + GOP (BGOP) on resting metabolic rate, body composition, perceptual indicators of mood and affect, and cardiometabolic markers in overweight and obese men and women. MethodsHealthy men and women (43.2 ± 11.4 years, 169.4 ± 7.6 cm, 90.3 ± 15.6 kg, 31.4 ± 4.4 kg∙m-2) completed a weekly exercise program and followed a calorie-restrictive diet and were randomly assigned in a double-blind and blocked manner according to sex and DXA lean mass to consume daily either a placebo (PLA) (n=12 [11F, 1M]), 500 mg L-BAIBA (L-BAIBA: MitoBurn™, NNB Nutrition) (n=13 [9F, 4M]), or 500 mg L-BAIBA + 40 mg GOP (BGOP: CaloriBurn™, NNB Nutrition) (n=12 [8F, 4M]). After 0, 14, 28, and 56 days of supplementation, participants were evaluated for changes in body mass, body composition using dual-energy x-ray absorptiometry (DXA), resting metabolic rate, perceptual indicators of hunger, appetite, energy, focus, attention, and concentration using 100-mm anchored visual analog scales (VAS) and mood using the Profile of Mood States along with evaluation of selected cardiometabolic markers. Dietary intake was evaluated using 3-day dietary recalls using ASA24 throughout the study. Mixed factorial ANOVAs with repeated measures assessed the main and interaction effects. A p-value of 0.05 was used to determine statistical outcomes.ResultsNo statistically significant group × time interactions (p>0.05) were found for body mass, resting metabolic rate, DXA fat mass, DXA fat-free mass, DXA % fat, VAS ratings for appetite, energy, focus, attention, and concentration, resting heart rate, systolic blood pressure, diastolic blood pressure, glucose, or lipid panel component. A significant group × time interaction (p = 0.011) for hunger VAS ratings was observed. Compared with PLA, BAIBA reported reduced hunger ratings after 14, 28, and 56 days of supplementation, while BGOP reported reduced hunger ratings after 28 days of supplementation. Conclusion Despite no accompanying changes in body composition, resting metabolic rate, or dietary intake, supplementation with BAIBA and BGOP reduced perceived hunger compared to PLA during the diet and exercise program.

Gosset, M, Coquart, A, Delaval, B, Catalano, J, Huou, G, Boufflers, M, Bozok, D, Bellanger, L, Douchet, T, Viroux, P, Jaffré, C, and Abaïdia, A-E. Compression garments and adaptations to plyometric training in soccer players: A randomized-controlled study. J Strength Cond Res XX(X): 000-000, 2026-The aim of this study was to analyze the effects of the chronic use of compression garments (CG) during a 6-week plyometric microcycle training block on training adaptations in soccer players. It was hypothesized that CG would have a beneficial effect on training adaptations, compared with placebo (PLA). Eighteen male soccer players (19.54 ± 1.39 years; 180.45 ± 5.25 cm; 71.14 ± 6.73 kg) from a reserve team of an elite professional club were randomly assigned to receive either CG or PLA for 24 hours after each plyometric session. The players participated in a plyometric training program: 2 sessions per week for 6 weeks. In a fully rested state, the players were tested before and after the training program on the following parameters: countermovement jump performance, One-leg sprint power, knee extensor strength, pennation angle of the calf muscles, creatine kinase levels, and perceived muscle soreness. The results were analyzed using a 2-factor mixed linear model. Countermovement jump performance showed a moderate, significant improvement in the CG group (d = 0.762), and a small, nonsignificant improvement in the PLA group (d = 0.344). One-leg power performance showed a large, significant improvement in the CG group (d = 1.690) and in the PLA group (d = 0.867). The results of this study show that the chronic use of CG for recovery does not negatively affect training adaptations and may improve power following a plyometric training program.