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Search Results (14,344)

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Keywords = randomized controlled trials

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15 pages, 483 KB  
Article
Combined Nutraceutical Supplementation and Pulsed Electromagnetic Field Therapy Enhances Early Pain Reduction and Bone Callus Formation After Distal Radius Fracture: A Randomized Controlled Trial
by Dalila Scaturro, Sofia Tomasello, Marika Triscari Barberi, Giuseppe Lo Re and Giulia Letizia Mauro
Nutrients 2026, 18(12), 2010; https://doi.org/10.3390/nu18122010 (registering DOI) - 20 Jun 2026
Abstract
Background: Distal radius fractures (DRFs) are common fragility fractures often associated with underlying osteoporosis. Objective: To evaluate the effect of nutraceutical supplementation in addition to pulsed electromagnetic field (PEMF) therapy on pain and early fracture healing. Methods: Sixty female patients were randomized into [...] Read more.
Background: Distal radius fractures (DRFs) are common fragility fractures often associated with underlying osteoporosis. Objective: To evaluate the effect of nutraceutical supplementation in addition to pulsed electromagnetic field (PEMF) therapy on pain and early fracture healing. Methods: Sixty female patients were randomized into two groups: Group A received PEMF therapy alone, while Group B received PEMF plus nutraceutical supplementation. The primary outcome was pain reduction (NRS). Secondary outcomes included biochemical markers and ultrasound-based callus formation. Results: At T1, Group B showed a trend toward greater pain reduction compared with Group A (mean difference −0.57; p = 0.007) and higher bone alkaline phosphatase levels (p = 0.0002). A higher proportion of patients reached minimal clinically important difference (MCID) in Group B (60% vs. 30%, p = 0.02). Conclusions: Nutraceutical supplementation in addition to PEMF was associated with improved short-term outcomes; however, due to the absence of a non-PEMF control group, the independent effect of PEMF cannot be determined. Full article
20 pages, 1133 KB  
Systematic Review
Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer: A Systematic Review with Meta-Analysis of Single-Arm Efficacy and Integration of Randomized and Real-World Evidence
by Marcelino Pérez-Bermejo, Marcelo Mazón-Albalate, María Teresa Murillo-Llorente, Javier Pérez-Murillo, María Ester Legidos-García, Francisco Tomás-Aguirre, Alma María Palau-Ferré, Miriam Martínez-Peris and Ignacio Ventura
Cancers 2026, 18(12), 2005; https://doi.org/10.3390/cancers18122005 (registering DOI) - 20 Jun 2026
Abstract
Background/Objectives: Metastatic triple-negative breast cancer (mTNBC) carries a poor prognosis and limited treatment options. Sacituzumab govitecan (SG), an anti-Trop-2 antibody–drug conjugate, has shown activity in this setting, but a quantitative synthesis integrating randomized and real-world evidence—particularly in underrepresented subgroups—was lacking. We aimed to [...] Read more.
Background/Objectives: Metastatic triple-negative breast cancer (mTNBC) carries a poor prognosis and limited treatment options. Sacituzumab govitecan (SG), an anti-Trop-2 antibody–drug conjugate, has shown activity in this setting, but a quantitative synthesis integrating randomized and real-world evidence—particularly in underrepresented subgroups—was lacking. We aimed to summarize the comparative benefit of SG, which derives from a single randomized trial, and to assess whether trial-level efficacy is consistent with the activity observed in routine practice. Methods: Following PRISMA 2020, we searched PubMed/MEDLINE and Web of Science (January 2017–April 2026) for trials and observational cohorts of SG monotherapy in mTNBC. Comparative effects were taken from randomized data; single-arm efficacy (objective response rate [ORR], clinical benefit rate [CBR], median progression-free [PFS], and overall survival [OS]) was pooled using random-effects models. Risk of bias was assessed with RoB 2 and ROBINS-I. The review was registered in the Open Science Framework. Results: Nine studies (1242 patients; 980 SG-treated) were included: one randomized trial (ASCENT), two single-arm trials, and six real-world cohorts. In ASCENT, SG improved PFS (hazard ratio [HR] 0.41, 95% CI 0.33–0.63) and OS (HR 0.51, 0.42–0.64). Pooled ORR was 31.1% (28.0–34.4), and CBR was 42.2% (37.7–46.8), with the median PFS being 4.8 months (4.4–5.3) and OS being 11.0 months (9.3–13.0); trial-derived and real-world estimates were concordant. The benefit persisted in older patients (HR 0.25) and Black women (HR 0.44) but not in those with brain metastases (HR 0.68, 0.38–1.23). Conclusions: SG shows clinically meaningful activity in mTNBC that is broadly consistent between controlled trials and routine practice. Comparative superiority over chemotherapy rests on a single randomized trial (ASCENT); the pooled single-arm estimates describe activity and its consistency rather than a comparative effect. Full article
(This article belongs to the Section Cancer Metastasis)
33 pages, 2312 KB  
Article
Telemonitoring in Inflammatory Bowel Disease: Findings from the TIGE-Rus Randomized Controlled Trial
by Dina A. Akhmedzyanova, Yuliya F. Shumskaya, Kristina V. Charaya, Yuriy A. Vasilev, Anton V. Vladzymyrskyy, Yulya A. Alymova, Ivan A. Blokhin, Roman V. Reshetnikov, Irina V. Kuprina, Olga V. Taschyan, Marta V. Yurazh and Marina G. Mnatsakanyan
J. Clin. Med. 2026, 15(12), 4800; https://doi.org/10.3390/jcm15124800 (registering DOI) - 20 Jun 2026
Abstract
Background: Telemedicine is increasingly used in inflammatory bowel disease (IBD), but its effects on quality of life (QoL) and psychological outcomes remain unclear. Objectives: This study aimed to evaluate the impact of 6-month telemonitoring on QoL, disease activity, treatment adherence, psychological well-being, [...] Read more.
Background: Telemedicine is increasingly used in inflammatory bowel disease (IBD), but its effects on quality of life (QoL) and psychological outcomes remain unclear. Objectives: This study aimed to evaluate the impact of 6-month telemonitoring on QoL, disease activity, treatment adherence, psychological well-being, patient satisfaction, and healthcare utilization. Methods: This randomized, open-label, single-center study conducted in Russia (July 2023–December 2024) included adults with ulcerative colitis or Crohn’s disease, who were assigned 1:1 to telemonitoring or standard care. The intervention involved monthly remote assessments and access to a web-based platform containing educational information, disease activity assessment, and a chat with a gastroenterologist. The primary outcome was health-related QoL (SIBDQ). Exploratory outcomes included general QoL (WHOQOL-26), psychological well-being (HADS), alexithymia (TAS-26), visceral sensitivity (VSI), treatment adherence (GMAS), patient satisfaction (PSQ-18), achievement of clinical remission, and healthcare utilization. Results: Sixty-eight patients completed the study (32 intervention, 36 control). Telemonitoring was associated with lower anxiety levels (β = −1.76, p = 0.021), reduced visceral sensitivity (β = −5.08, p = 0.039), and higher medication adherence (β = 1.75, p = 0.008). No significant associations were observed for SIBDQ, WHOQOL-26 domains, depressive symptoms, alexithymia, achievement of clinical remission, or patient satisfaction with care (p > 0.05). Patients in the telemonitoring group also required fewer outpatient visits (p < 0.001), with no difference in hospitalizations. Within-group analysis demonstrated improvements in QoL, treatment adherence, visceral sensitivity, and disease activity in the telemonitoring group, but not in the controls. Conclusions: Six-month telemonitoring in IBD was associated with lower anxiety, reduced visceral sensitivity, improved treatment adherence, and fewer outpatient visits. The health-related QoL assessed by the SIBDQ did not differ compared to standard care. No clear clinical disadvantage compared with standard care was detected during the study period. Full article
17 pages, 998 KB  
Article
The Mediation Role of Relatedness and Competence for Patient Activation: A Longitudinal Study of Older Adults with Chronic Illness
by Monica Kaltenbrunner, Maria Flink, Amanda Hellström and Mirjam Ekstedt
Healthcare 2026, 14(12), 1783; https://doi.org/10.3390/healthcare14121783 (registering DOI) - 20 Jun 2026
Abstract
Background: Patient activation is associated with both health outcomes and the utilization of healthcare resources. Since various factors influence activation levels among older ill adults, further exploration of this topic is needed. Specifically, we aim to examine the extent to which changes [...] Read more.
Background: Patient activation is associated with both health outcomes and the utilization of healthcare resources. Since various factors influence activation levels among older ill adults, further exploration of this topic is needed. Specifically, we aim to examine the extent to which changes over time in self-rated symptoms of depression are associated with changes in patient activation and to what extent self-rated health status and satisfaction of basic psychological needs (autonomy, relatedness, and competence) have a mediation effect. Methods: A longitudinal and correlational design was employed in which two hundred and seven participants with heart failure or chronic obstructive pulmonary disease were recruited from two hospitals in the middle of Sweden. The sample used in this study is the same as that used in a randomized controlled trial. A questionnaire was administered at baseline, and at 30-, 90-, and 180 days post-discharge, involving ratings of depression, patient activation, self-rated health, and satisfaction of basic psychological needs (autonomy, relatedness, and competence). As the results from the original study showed no difference between the two randomized groups in patient activation, the analysis in this study was conducted using a combined sample in which the intervention and control groups were merged. For estimation of the direct effects and the components of indirect effects, we employed multilevel modeling using a linear mixed model, and to test mediation, the stand-alone program RMediation was used. Results: Over time, increases in depressive symptoms were associated with reduced patient activation, with this relationship mediated by declines in relatedness and competence. No evidence was found showing that autonomy or self-rated health had a mediation effect. Conclusions: The results indicate that older chronically ill individuals may benefit from interventions targeting psychological mediators to improve and sustain activation. Full article
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13 pages, 724 KB  
Article
Meal-Specific and Qualitative Patterns of Ultra-Processed Food Consumption in Adults with Food Addiction and Excess Weight: A Secondary Cross-Sectional Analysis of a Randomized Controlled Trial
by Débora C. Ferro, Marianna V. C. Rocha, Thayná X. R. de Oliveira, Mariana K. de B. Lima, Cellyne V. da Silva and Nassib B. Bueno
Obesities 2026, 6(3), 43; https://doi.org/10.3390/obesities6030043 (registering DOI) - 20 Jun 2026
Abstract
Evidence suggests that individuals with food addiction (FA) consume more ultra-processed foods (UPFs), but gaps remain regarding which types and at which meals. This study compared the types of UPFs consumed and the meals with the highest UPF density between individuals with and [...] Read more.
Evidence suggests that individuals with food addiction (FA) consume more ultra-processed foods (UPFs), but gaps remain regarding which types and at which meals. This study compared the types of UPFs consumed and the meals with the highest UPF density between individuals with and without FA. Food intake was assessed via 24 h dietary recalls, and foods were classified via the NOVA system and disaggregated into subgroups. FA was identified using the modified Yale Food Addiction Scale 2.0. Linear regression compared UPF consumption between groups, adjusted for confounders. A total of 144 participants were analyzed, and 26 (18%) met the criteria for FA. In multivariable analysis, the FA group had a higher UPF energy contribution (in %kcal) than those without FA (28.30% vs. 22.30%; p = 0.02), and a lower consumption of unprocessed and minimally processed foods (47.40% vs. 54.40%; p = 0.03). Higher consumption of ultra-processed sweets and confectionery (10.39% vs. 4.18%; p = 0.001) and greater UPF intake as part of the afternoon snack (8.34% vs. 4.67%; p = 0.005) were also observed in the FA group. UPF consumption differed between groups. Individuals with FA showed a sweets-dominant, meal-specific pattern with a higher intake of ultra-processed sweets and confectionery, concentrated during the afternoon snack. Full article
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32 pages, 667 KB  
Article
Clinical Status and Salivary aMMP-8 Evaluation of 0.12% Chlorhexidine Versus MicroRepair® ABX Mouthwash in the Non-Surgical Management of Plaque-Induced Gingivitis: A Randomized Controlled Trial
by Andrea Scribante, Maurizio Pascadopoli, Matteo Pellegrini, Cinzia Casu, Eva Massazzi and Andrea Butera
Dent. J. 2026, 14(6), 383; https://doi.org/10.3390/dj14060383 (registering DOI) - 20 Jun 2026
Abstract
Objectives: To compare the adjunctive efficacy of a MicroRepair® mouthwash containing an antibacterial complex (ABX), composed of cetylpyridinium chloride, magnolol, and honokiol, with 0.12% chlorhexidine (CHX) in the management of generalized plaque-induced gingivitis, assessing clinical periodontal parameters, salivary activated matrix metalloproteinase-8 [...] Read more.
Objectives: To compare the adjunctive efficacy of a MicroRepair® mouthwash containing an antibacterial complex (ABX), composed of cetylpyridinium chloride, magnolol, and honokiol, with 0.12% chlorhexidine (CHX) in the management of generalized plaque-induced gingivitis, assessing clinical periodontal parameters, salivary activated matrix metalloproteinase-8 (aMMP-8) levels, and patient-reported outcomes over 6 months. Methods: A randomized, controlled, parallel-group clinical trial included 40 systemically healthy adults with generalized gingivitis and was reported in accordance with CONSORT 2025 guidelines. Following professional oral hygiene according to the Guided Biofilm Therapy (GBT) protocol, participants were randomly allocated to ABX or 0.12% CHX, used twice daily for 14 days. Clinical parameters, including Full-Mouth Bleeding Score (FMBS, primary outcome), Full-Mouth Plaque Score (FMPS), Probing Pocket Depth (PPD), Clinical Attachment Level (CAL), Gingival Recession (REC), and Modified Lobene Stain Index (MLSI), were recorded at baseline, 2 weeks, 1, 3, and 6 months. Salivary aMMP-8 levels were assessed at baseline and 2 weeks. Heavy smokers were excluded, and smoking status was evaluated as a potential covariate. Non-parametric tests were applied (p < 0.05). Results: Both groups showed significant reductions in FMBS and FMPS over time (p < 0.05), with no intergroup differences for the primary outcome at any follow-up at the patient level. Patient-level analyses did not reveal consistent differences across secondary parameters. At the tooth level, lower FMPS values were observed in the trial group at 2 weeks and 1 month (p < 0.05), with earlier PPD reduction. CAL, and REC remained stable. Salivary aMMP-8 levels decreased significantly in both groups without intergroup differences. Patient-reported outcomes were comparable. Smoking status was balanced between groups and was not significantly associated with treatment allocation or the main clinical outcomes. Conclusions: No significant differences were observed between ABX and CHX for the main clinical and molecular outcomes, supporting its potential use as an adjunct in gingivitis management. Full article
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11 pages, 454 KB  
Article
The Effect of Night-Time Feeding on Steer Performance After Terminal Sort
by Madeline R. Mancke, Brad J. White, Eduarda M. Bortoluzzi and Robert L. Larson
Animals 2026, 16(12), 1912; https://doi.org/10.3390/ani16121912 (registering DOI) - 20 Jun 2026
Abstract
Heat stress occurs when total environmental and metabolic heat production is greater than an animal’s ability to dissipate that heat. Heat stress negatively impacts feeder cattle performance and welfare. Limited research has been conducted to determine if feeding cattle in the evening, thereby [...] Read more.
Heat stress occurs when total environmental and metabolic heat production is greater than an animal’s ability to dissipate that heat. Heat stress negatively impacts feeder cattle performance and welfare. Limited research has been conducted to determine if feeding cattle in the evening, thereby shifting their metabolic heat production to a cooler period of the day, can help mitigate heat stress. This pen-level randomized controlled trial evaluated the effects of evening feeding (PM; feedings at 2000, 2300, and 0200 h; n = 24 pens) versus morning feeding (AM; feedings at 0500, 0800, and 1200 h; n = 24 pens) on terminally sorted steer performance in a commercial feedyard in the Pacific Northwest. Data collection included feed delivery, water consumption, health events, open mouth breathing prevalence, and carcass traits. Linear and generalized linear mixed-effects models were used to determine potential differences between treatment group and temperature-humidity index (THI; <80 versus ≥80). Only 14% of the total study days had a THI ≥ 80, indicating little to no heat stress impacts. There were no differences found between PM and AM for any outcome (p < 0.05). Regardless of treatment group, water consumption tended (p = 0.07) to increase, and open mouth breathing significantly (p < 0.05) increased on days with THI ≥ 80. Further research is warranted to assess evening feeding as a heat stress mitigation strategy in a feedyard setting. Full article
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28 pages, 567 KB  
Systematic Review
Effects of Curcumin Supplementation on Exercise Recovery, Oxidative Stress, Inflammation, Muscle Damage, and Performance in Exercise and Sport Contexts: A Systematic Review
by Jesús Lloret-Gil, Desirée Victoria-Montesinos and Francisco Javier Martínez-Noguera
Nutrients 2026, 18(12), 1992; https://doi.org/10.3390/nu18121992 (registering DOI) - 19 Jun 2026
Abstract
Background/Objectives: Curcumin has been proposed as a nutritional strategy to support exercise recovery through antioxidant and anti-inflammatory actions. However, trials differ in sport context, training status, supplementation timing, dose, formulation, and methodological control. This systematic review evaluated its effects on recovery outcomes in [...] Read more.
Background/Objectives: Curcumin has been proposed as a nutritional strategy to support exercise recovery through antioxidant and anti-inflammatory actions. However, trials differ in sport context, training status, supplementation timing, dose, formulation, and methodological control. This systematic review evaluated its effects on recovery outcomes in active individuals and athletes, with particular attention to the applicability of the evidence to real-world sport settings. Methods: PubMed, Scopus, Web of Science, SPORTDiscus, and Cochrane Library/CENTRAL were searched from 2012 to June 2026. Randomized double-blind placebo-controlled trials were eligible when they evaluated oral curcumin, curcuminoids, Curcuma-derived preparations with a specified curcumin dose, or curcumin combined only with bioavailability enhancers. Studies using artificial muscle-damage protocols, clinical populations, non-randomized designs, or combined bioactive interventions were excluded. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale, supplemented by a Cochrane Risk of Bias 2 (RoB 2) assessment and a Grading of Recommendations Assessment, Development and Evaluation (GRADE) certainty-of-evidence evaluation. Owing to heterogeneity, findings were synthesized narratively by outcome domain, supplementation timing, formulation type, exercise context, and training status. Results: Fifteen trials were included. Favorable effects were reported in 6/7 studies assessing oxidative stress, 4/6 assessing muscle damage, 3/8 assessing inflammation, 3/7 assessing subjective recovery, soreness, or fatigue, and 4/8 assessing physical or athletic performance. However, effects varied substantially according to population, exercise context, biomarker selection, timing of assessment, and formulation type. The certainty of evidence was low for oxidative stress and very low for muscle damage, inflammation, subjective recovery/soreness/fatigue, and performance. Conclusions: Curcumin supplementation may support selected aspects of exercise recovery, particularly oxidative stress responses. However, these findings should be interpreted cautiously because the evidence derives mostly from small trials with heterogeneous populations, exercise protocols, supplementation regimens, formulations, biomarkers, and assessment time points. Evidence for muscle damage, inflammation, subjective recovery, fatigue, and performance remains inconsistent, and further well-controlled trials in trained and high-performance athletes are needed before practical recommendations can be established. Full article
22 pages, 2402 KB  
Article
Clinical Outcomes of Plasma-Assisted Saline Irrigation in Nonsurgical Root Canal Treatment: A Preliminary Retrospective Cohort Study
by Young-Hee Kim, Jeong-Hyo Lyu, Hyun-Sook Chung, Sang-Yoon Park, Sang-Min Yi, Soo-Hwan Byun, Sung-Woon On, Jae-Seo Lee, Dong-Jun Kim and Byoung-Eun Yang
Biomedicines 2026, 14(6), 1389; https://doi.org/10.3390/biomedicines14061389 (registering DOI) - 19 Jun 2026
Abstract
Background: Effective root canal disinfection is essential for successful nonsurgical root canal treatment (RCT). Although sodium hypochlorite (NaOCl) remains the standard irrigant, it carries a risk of chemical tissue injury if extruded beyond the root canal system and may have limited penetration into [...] Read more.
Background: Effective root canal disinfection is essential for successful nonsurgical root canal treatment (RCT). Although sodium hypochlorite (NaOCl) remains the standard irrigant, it carries a risk of chemical tissue injury if extruded beyond the root canal system and may have limited penetration into anatomically complex regions. Underwater discharge plasma (UDP) generates reactive oxygen and nitrogen species (RONS) through high-frequency, high-voltage electrical discharge in aqueous media, and preclinical and in vitro studies have reported broad-spectrum antimicrobial activity. This study evaluated the clinical and radiographic outcomes of nonsurgical RCT performed using physiological saline-based UDP irrigation without NaOCl in a heterogeneous real-world clinical cohort. Methods: This single-center retrospective cohort study included 186 teeth from 134 patients treated with the PLAZEN RCT® UDP device and physiological saline irrigation, without NaOCl. The median follow-up period was 16 months. Radiographic outcomes were assessed using the Periapical Index (PAI) system, and treatment success was evaluated according to prespecified Strict and Loose criteria incorporating both radiographic and clinical findings. Stratified analysis was performed according to preoperative PAI score: Group A (PAI 1–2) and Group B (PAI 3–5). UDP-related adverse events, defined as thermal tissue injury caused by discharge heat, were ascertained through retrospective review of clinical records, operative notes, and serial periapical radiographs. Results: Among the 186 treated teeth, radiographic outcomes were classified as Healed (85.5%), Healing (3.8%), and Unhealed (10.8%). Overall Strict and Loose success rates were 79.6% and 82.3%, respectively. Initial treatment showed numerically higher success rates than retreatment. In the stratified analysis, Group A showed an 84.1% success rate with 100% tooth survival, whereas Group B demonstrated Strict and Loose success rates of 68.5% and 83.3%, respectively. Exploratory multivariable analysis showed that periodontal pocket depth > 3 mm was the most consistent factor associated with lower odds of treatment success, whereas associations involving canal obliteration and higher preoperative PAI score were less stable across sensitivity analyses and should be interpreted with caution. No UDP-related adverse events were recorded during follow-up. Attrition sensitivity analyses were performed, and the outcome estimates should be interpreted with caution, given the retrospective design and substantial loss to follow-up. Conclusions: In this preliminary observational cohort, physiological saline-based UDP irrigation without NaOCl was associated with favorable observed periapical healing outcomes and no recorded UDP-related adverse events over a median follow-up of 16 months. However, loss to follow-up was substantial; when all 116 teeth lost to follow-up were classified as treatment failures, the worst-case Strict success rate decreased to 49.0%. Therefore, these findings should be interpreted as preliminary descriptive evidence of clinical feasibility rather than as evidence of comparative efficacy or definitive clinical safety. Adequately powered randomized controlled trials with concurrent NaOCl control arms and long-term follow-up are warranted to evaluate the comparative effectiveness, safety, and reproducibility of physiological saline-based UDP irrigation protocols. Full article
(This article belongs to the Special Issue Biomedicine in Dental and Oral Rehabilitation)
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13 pages, 270 KB  
Systematic Review
Glucagon-like Peptide-1 Receptor Agonists and Alcohol Use Outcomes: A Systematic Review of Clinical Evidence
by Ibrahim K. Altami, Eyad A. Alabdulrahim and Osamah M. Alfayez
J. Clin. Med. 2026, 15(12), 4781; https://doi.org/10.3390/jcm15124781 (registering DOI) - 19 Jun 2026
Abstract
Background and Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for type 2 diabetes and obesity treatment and may influence reward-related behaviors, including alcohol use. This study aimed to evaluate the effects of GLP-1RAs on alcohol consumption and related outcomes in [...] Read more.
Background and Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for type 2 diabetes and obesity treatment and may influence reward-related behaviors, including alcohol use. This study aimed to evaluate the effects of GLP-1RAs on alcohol consumption and related outcomes in adults with alcohol use or alcohol use disorder (AUD). Methods: A systematic review was conducted following PRISMA 2020 guidelines. PubMed and Web of Science were searched from inception to December 2025. Eligible studies included randomized controlled trials (RCTs), secondary analyses of RCTs, and observational studies reporting quantitative alcohol consumption outcomes. Data extraction and risk of bias assessment (RoB 2 and ROBINS-I) were performed independently by two reviewers. Results: Five studies (n = 49,892) were included, comprising three RCT-based analyses and one large cohort study. Semaglutide and dulaglutide were associated with modest reductions in alcohol consumption and craving in several studies, with statistically significant improvements in selected behavioral outcomes. In contrast, exenatide did not demonstrate significant effects in the overall AUD population, with signals limited to subgroups. The cohort study showed small but statistically significant reductions in AUDIT-C scores following GLP-1RA initiation. Objective measures (e.g., PEth, breath alcohol concentration) showed reductions in selected contexts but were reported in a few studies. Conclusions: GLP-1RAs may be associated with modest reductions in alcohol consumption, but evidence remains limited and heterogeneous. Larger, well-designed RCTs are needed to define their role in the management of AUD. Full article
(This article belongs to the Section Endocrinology & Metabolism)
11 pages, 1754 KB  
Review
TWO2 Therapy Demonstrates Clinically Meaningful Long-Term Outcomes Compared to Other Advanced Wound Care Modalities: Real-World Evidence Supported by Mechanistic and RCT Clinical Data
by Anahita Dua, Naseer Ahmad, Cyaandi R. Dove, Matthew J. Regulski, Sara Rose-Sauld and Matthew G. Garoufalis
J. Clin. Med. 2026, 15(12), 4780; https://doi.org/10.3390/jcm15124780 (registering DOI) - 19 Jun 2026
Abstract
Background/Objectives: Chronic diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) remain a major source of morbidity, healthcare utilization, and limb loss, despite adherence to established standards of care protocols and the widespread availability of advanced wound technologies. Many advanced modalities only [...] Read more.
Background/Objectives: Chronic diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) remain a major source of morbidity, healthcare utilization, and limb loss, despite adherence to established standards of care protocols and the widespread availability of advanced wound technologies. Many advanced modalities only target isolated aspects of wound healing and fail to address the complex, interdependent pathophysiology of chronic wounds, particularly tissue hypoxia, edema, impaired microcirculation, and persistent inflammation. Cyclical Pressurized Topical Wound Oxygen (TWO2) therapy is a home-based, multimodal intervention that combines humidified topical oxygen delivery with cyclical non-contact compression to address these core drivers simultaneously. Methods: This review synthesizes mechanistic rationale and evidence from randomized controlled trials, long-term venous ulcer studies, and real-world comparative effectiveness analyses. Emphasis is placed on the large cohort study by Yellin et al., which directly compared TWO2 with other advanced modalities including negative pressure wound therapy (NPWT), skin substitutes, and growth factor therapies. Results: Across these studies, TWO2 therapy is consistently associated with improved healing durability, reduced recurrence, and substantial reductions in hospitalization and amputation rates compared with both standard care and advanced wound therapies. Conclusions: The convergence of randomized and real-world evidence supports TWO2 therapy as a clinically meaningful and mechanism-driven adjunctive treatment option for patients with chronic, high-risk lower-extremity wounds. Full article
(This article belongs to the Special Issue New Advances in Wound Healing and Skin Wound Treatment)
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21 pages, 900 KB  
Review
The Gut-Bone Axis and Skeletal Health: Regulatory Mechanisms and Therapeutic Applications of Plant-Derived Bioactive Compounds
by Tianzhu Zhang, Yufei Li, Jiahui Pei, Qingxia Zhang, Fengyun Lin and Shuzhen Li
Biomolecules 2026, 16(6), 912; https://doi.org/10.3390/biom16060912 (registering DOI) - 19 Jun 2026
Abstract
The gut microbiota and its metabolites, as components of the gut–bone axis, play a pivotal role in regulating skeletal homeostasis through the bidirectional communication network. In this systematic review, evidence was collected from mainstream databases following standardized inclusion/exclusion criteria for screening, to comprehensively [...] Read more.
The gut microbiota and its metabolites, as components of the gut–bone axis, play a pivotal role in regulating skeletal homeostasis through the bidirectional communication network. In this systematic review, evidence was collected from mainstream databases following standardized inclusion/exclusion criteria for screening, to comprehensively retrieve and screen eligible studies from multiple mainstream databases according to standardized inclusion and exclusion criteria, and systematically summarize current research progress on plant-derived bioactive compounds targeting the gut–bone axis for skeletal health regulation. This review systematically explores the underlying mechanisms of the gut–bone axis and critically evaluates the regulatory effects and therapeutic potential of plant-derived bioactive compounds. Particular attention is given to targeted interventions involving prebiotics, probiotics, synbiotics, and plant-rich diets or functional foods. Among these interventions, synbiotics represent the most successful strategy and show the most prominent therapeutic possibilities in bone-related disorders. Different from single prebiotics (only nourish endogenous intestinal microbes), individual probiotics (easy to be degraded in gastrointestinal tract with poor colonization) and ordinary plant-rich diets (unfixed effective dosage and weak targeting property), synbiotics combine prebiotic carriers and viable probiotic strains to produce complementary advantages, which is the core reason for its outstanding therapeutic prospect against bone diseases. Synbiotics exert synergistic effects on gut microecology, mineral absorption, and immune regulation, leading to more robust and consistent improvements in bone health than single prebiotics, probiotics, or general plant-rich diets. They have been verified in preclinical and clinical studies to ameliorate osteoporosis and related skeletal diseases via the gut–bone axis. These strategies offer novel insights into the prevention and treatment of bone metabolic disorders, such as osteoporosis, by targeting the gut–bone axis with phytochemicals. Key outcomes of this review include that synbiotics, soy isoflavones, naringin, curcumin, and resveratrol effectively improve bone mineral density, restore gut microbiota balance, and inhibit pathological bone resorption via the gut–bone axis. Collectively, the above bioactive substances realize bone protection mainly by reshaping gut flora, elevating mineral uptake and suppressing excessive osteoclast activity. Representative cases include soy isoflavones mitigating estrogen-deficient bone loss in OVX models, naringin improving the trabecular microarchitecture, and probiotic BL-11 promoting longitudinal bone growth in children. Future directions will focus on clarifying dose–response relationships, developing standardized synbiotic formulations, constructing microbiome-guided precision diets, and conducting large-sample randomized controlled trials to translate plant-derived compounds into clinical therapies. Full article
(This article belongs to the Section Natural and Bio-derived Molecules)
22 pages, 3060 KB  
Systematic Review
Dose-Response Effect of Oral Caffeine Use on Aerobic Exercise Performance: A Systematic Review and Meta-Analysis
by Gabriel L. Martins, Juliana M. Aparecido, Marcelo L. Marquezi, Caroline S. Frientes, Leonardo R. Miedes, Matheus S. Fornel, Tiago Fernandes and Antônio Herbert Lancha
Nutrients 2026, 18(12), 1989; https://doi.org/10.3390/nu18121989 - 19 Jun 2026
Abstract
Background/Objective: Caffeine has demonstrated ergogenic effects across various doses (2–9 mg·kg−1). However, aerobic responses to caffeine vary substantially, with time-trial performance ranging from ~–3% to +16%. Given that higher doses may increase adverse effects without clear additional benefits, this review examined [...] Read more.
Background/Objective: Caffeine has demonstrated ergogenic effects across various doses (2–9 mg·kg−1). However, aerobic responses to caffeine vary substantially, with time-trial performance ranging from ~–3% to +16%. Given that higher doses may increase adverse effects without clear additional benefits, this review examined the effects of low (≤3 mg·kg−1), moderate (4–6 mg·kg−1), and high (>6 mg·kg−1) caffeine doses on time-trial performance. Methods: A systematic review and meta-analysis of randomized, placebo-controlled trials was conducted using PubMed, Embase, and Virtual Health Library databases. Eligible studies included healthy adults (18–59 years) acutely ingesting oral anhydrous caffeine before aerobic time-trial tests, with performance outcomes measured exclusively as time-to-completion variables. Data were pooled using standardized mean differences (SMDs) and 95% confidence intervals under random-effects models, and risk of bias was assessed using the Cochrane Risk of Bias tool. Results: Forty-eight studies (689 participants) met the inclusion criteria. Both low and moderate caffeine doses significantly reduced time-trial completion time relative to placebo. Low doses produced a standardized mean difference of −0.27 (95% CI: −0.44 to −0.11; p = 0.001), whereas moderate doses resulted in an SMD of −0.52 (95% CI: −0.77 to −0.28; p < 0.0001). No studies evaluating high caffeine doses (>6 mg·kg−1) and reporting time-to-completion outcomes met the inclusion criteria. Subgroup analyses demonstrated similar ergogenic effects in both trained and highly trained individuals consuming moderate caffeine doses. Conclusions: This is the first meta-analysis specifically focused on aerobic time-trial performance to suggest that pre-exercise ingestion of low caffeine doses (1.3–3 mg·kg−1) may enhance endurance performance by reducing time-trial completion time. Notably, the use of moderate caffeine doses (4–6 mg·kg−1) appears to produce a more consistent ergogenic effect. Full article
(This article belongs to the Special Issue Individualised Caffeine Use in Sport and Exercise)
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17 pages, 2661 KB  
Systematic Review
Health Effects of Plant-Based Diets in People with Overweight or Obesity: A Systematic Review and Meta-Analysis
by Ildikó Csölle, Viktória Cseh, Gábor Veres, László Czina, Daniela Kuellenberg de Gaudry, Dávid U. Nagy, Almut Georgi and Szimonetta Lohner
Nutrients 2026, 18(12), 1987; https://doi.org/10.3390/nu18121987 - 19 Jun 2026
Abstract
Background/Objectives: Nutrition plays a core role in chronic disease management, and there is growing interest in the health impact of plant-based diets (PBDs) in people with overweight or obesity. We conducted this systematic review and meta-analysis to summarize the evidence on the health [...] Read more.
Background/Objectives: Nutrition plays a core role in chronic disease management, and there is growing interest in the health impact of plant-based diets (PBDs) in people with overweight or obesity. We conducted this systematic review and meta-analysis to summarize the evidence on the health effect of PBDs compared to omnivorous diets in overweight or obese individuals. Methods: We searched the databases Cochrane Central Register of Controlled Trials, MEDLINE, Embase, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform from inception to 3 January 2024. Two review authors independently screened studies for eligibility, extracted data, evaluated the risk of bias, and rated the certainty of the evidence using GRADE. This study is registered with PROSPERO, CRD42021225525. We used random-effects meta-analysis to analyze data. Results: Of 2664 records identified, 10 randomized controlled trials (RCTs) and six ongoing studies met the inclusion criteria. The available evidence suggests little to no difference between plant-based and omnivorous diets for body weight, systolic blood pressure, diastolic blood pressure, serum glucose, serum insulin, insulin sensitivity, total cholesterol, triglyceride, HDL cholesterol and body fat mass. Plant-based diets may slightly reduce LDL cholesterol. They may also reduce BMI and HbA1c, although the certainty of the evidence is very low. Longer-duration dietary interventions (14 weeks or more) showed greater improvements in BMI, LDL cholesterol and HbA1c. Conclusions: Plant-based diets may represent a dietary option for people with overweight or obesity and may support modest improvements in selected cardiometabolic outcomes, although the available evidence is limited and uncertain. Most outcomes showed little or no difference between PBDs and comparison diets, while the observed effects on BMI and HbA1c were supported by very low certainty evidence. Full article
(This article belongs to the Section Nutrition and Obesity)
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15 pages, 998 KB  
Article
Perceived Exertion Is Associated with Cardiovascular Strain but Not Glycemic Response to Gym-Based Exercise in Adults with Type 1 Diabetes: An Exploratory Randomized Crossover Trial
by José Adevalton Feitosa Gomes, Anthony Rodrigues de Vasconcelos, José Roberto Andrade do Nascimento Júnior, Ysadora Verena Ribeiro de Souza, Fabiana Oliveira dos Santos Camatari, Bruno Bavaresco Gambassi, Manoel da Cunha Costa, Paulo Adriano Schwingel and Jorge Luiz de Brito Gomes
Int. J. Environ. Res. Public Health 2026, 23(6), 814; https://doi.org/10.3390/ijerph23060814 (registering DOI) - 19 Jun 2026
Abstract
Adults with type 1 diabetes mellitus (T1DM) face elevated cardiovascular risk, and regular exercise is a key non-pharmacological mitigation strategy. However, safe prescription requires cardiovascular and glycemic monitoring, often unfeasible in real-world gyms. Low-cost psychophysiological tools (ratings of perceived exertion—RPE and enjoyment) may [...] Read more.
Adults with type 1 diabetes mellitus (T1DM) face elevated cardiovascular risk, and regular exercise is a key non-pharmacological mitigation strategy. However, safe prescription requires cardiovascular and glycemic monitoring, often unfeasible in real-world gyms. Low-cost psychophysiological tools (ratings of perceived exertion—RPE and enjoyment) may offer practical alternatives. This exploratory randomized crossover trial examined whether post-session RPE and enjoyment are associated with acute heart rate (HR) and capillary blood glucose (BG) responses to gym-based aerobic and resistance training. Twelve adults with T1DM (29.8 ± 7.8 years; HbA1c 7.7 ± 1.6%; LDL-c 119.5 ± 24.4 mg/dL) completed three ~30 min sessions: aerobic interval training (AE) and two resistance protocols (STA, STB). HR and BG were measured pre-, immediately post-, and 20 min post-exercise; RPE and enjoyment, post-session. Multiple linear regression, controlling for exercise session type, examined associations of RPE and enjoyment with resting HR, BG, and percentage of heart rate reserve (%HR). RPE was higher after STA and STB than AE (p < 0.001; η2p = 0.529), while enjoyment and %HR were similar across sessions. Neither variable was associated with resting HR or BG (all adjusted R2 < 0; all p > 0.05). Controlling for exercise session type, RPE was a significant positive predictor of %HR (β = 0.44, p = 0.044), whereas enjoyment was not (β = −0.06, p = 0.719); however, the overall %HR model did not reach statistical significance (adjusted R2 =0.119; F(4,31) = 2.183; p = 0.094). These exploratory findings suggest that RPE, but not enjoyment, may serve as a low-cost adjunct intensity marker to inform exercise prescription in adults with T1DM at elevated cardiovascular risk; however, replication in larger samples is needed before clinical recommendations can be drawn. Direct BG monitoring remains essential for safety. Full article
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