Introduction: Substance use disorders represent a critical global challenge, characterized by multifaceted etiologies often studied in isolation. Epigenetics provides a mechanism linking environmental exposures to biological susceptibility. This review synthesizes the most recent evidence (2023-2025) to analyze substance use disorders complexity through a holistic lens integrating epigenetic, psychological, socio-biological, spiritual, and legal perspectives. Material and Methods: Following PRISMA guidelines, a comprehensive search of databases (PubMed, Scopus, Web of Science, PsycINFO, EMBASE, Cochrane) was conducted. Ninety-four studies meeting inclusion criteria were analyzed. Data were extracted, and random-effects meta-analyses were performed where feasible. Results: Quantitative synthesis revealed significant effect sizes across all domains. Key findings include a strong association between trauma and substance use disorder severity (OR 2.45) and a novel meta-analytic link between trauma and specific epigenetic aberrations (standardized mean differences 0.75). Social support (OR 2.90), religiosity (hazzard ratio 0.65), decriminalization (RR 0.71), and improved access to Medication for opioid use disorder (OR 2.10) emerged as protective factors. Epigenetic studies demonstrated how adversity becomes biologically embedded. Significant cross-domain interactions were identified, with epigenetics acting as a central mediator between environmental experiences and biological outcomes. Conclusion: Evidence supports a holistic, integrated model of substance use disorders where epigenetic processes mediate the biological embedding of risk and resilience. Effective intervention requires breaking down disciplinary silos to simultaneously address psychological trauma, socio-environmental stressors, and their epigenetic influences. Future research must employ longitudinal designs to investigate the reversibility of epigenetic markers and evaluate multilevel interventions incorporating this biological perspective.

Parkinson disease (PD) pathogenesis remains incompletely understood; beyond nigrostriatal loss, nondopaminergic mechanisms including neurovascular unit dysfunction may contribute to disability. Cerebral small vessel disease (CSVD) burden reflects neurovascular dysfunction in the form of white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMB), and enlarged perivascular spaces (ePVS). In PD cohorts, CSVD burden correlates with worse motor and gait scores. The aim of the study was to explore whether patients with PD exhibit greater CSVD burden than healthy controls (HC). We conducted a PRISMA-conformant systematic review and meta-analysis of studies including adults with idiopathic PD and a HC group that presented data comparing CSVD burden in these 2 groups. Six databases (MEDLINE, Embase, CINAHL Plus, CENTRAL, Scopus, and Web of Science) were searched on May 14 and 15, 2024. Two reviewers independently screened records, extracted data, and assessed risk of bias, with discrepancies resolved by consensus. Continuous outcomes were pooled as standardized mean differences (SMD); dichotomous outcomes as odds ratios (ORs). We evaluated small-study effects for pooled analyses with 10 or more studies using funnel plots and Egger regression test. We examined 13,403 records. Forty-six studies (45 cross-sectional) met inclusion criteria, totaling 3,817 PD and 2,593 HC (mean ages: 66.9 and 66.5, respectively). WMH volume (k = 21) was higher in PD (SMD 0.36, 95% CI 0.11-0.62). Visual ratings also indicated higher WMH in PD: global (k = 14) SMD 0.27 (95% CI 0.08-0.46); periventricular (k = 11) SMD 0.32 (95% CI 0.12-0.51); deep (k = 8) SMD 0.20 (95% CI 0.09-0.31). Differences in CMB (k = 6; OR 1.18, 95% CI 0.57-2.42) and lacunes (k = 4; OR 1.48, 95% CI 0.58-3.78) were not significant. ePVS results were heterogeneous but trended toward greater burden in PD, most notably in the midbrain (k = 3; SMD 1.80, 0.15-3.44). Overall evidence quality was rated as low, reflecting the observational nature of the included studies. Our analysis showed PD to be associated with greater WMH burden and increased midbrain ePVS. Pooled differences in CMB and lacunes were not significant. Substantial heterogeneity and cross-sectional designs limit certainty; standardized imaging and prospective cohorts are needed to define mechanisms and clinical implications.

Sustainable and regulated educational-setting food interventions may support regular and appropriate nutritional intake, resulting in positive health outcomes. The aim of this review was to assess the strength of associations between educational-setting food interventions and health outcomes among students. The PubMed/MEDLINE, Embase, and Web of Science databases were searched systematically for studies that investigated the association on educational-setting feeding intervention and health outcomes. Students receiving vs those not receiving educational-setting feeding interventions were eligible. We extracted data on study characteristics, participants, feeding interventions, and health outcomes. Outcomes were aggregated and reported as mean difference (MD) or event rate (ER), along with 95% CIs, using a 1-stage approach and a random-effects model. We included 91 studies with a total of 47 241 students, of whom 25 220 received an educational-setting feeding intervention. Meta-analysis results indicated a significant association between educational-setting feeding intervention and higher hemoglobin (MD = 0.80; 95% CI, 0.73-0.88), body iron (MD = 1.60; 95% CI, 0.15-3.05), vitamin D (MD = 8.63; 95% CI, 6.46-10.81), zinc (MD = 1.19; 95% CI, 0.17-2.20), and soluble transferrin receptor (sTfR) (MD = -0.79; 95% CI, -1.42 to -0.15). Positive significant associations were also found for anthropometric parameters, including height, weight for age, height for age, and body mass index. No significant association with cognition was detected (MD = 1.27; 95% CI, -26 to 3.81). This work enhances the crucial role of educational-setting feeding interventions, highlighting their association with multiple health outcomes, and draws attention to the importance of integrated approaches to achieve better and more sustainable results. PROSPERO registration No. CRD420251027958.

Transtendon repair vs. tear completion in partial-thickness rotator cuff tears: systematic review and meta-analysis.

To compare the effects of continuous positive airway pressure (CPAP), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), their combination, and no active intervention on respiratory, sleepiness, and metabolic outcomes in adults with obstructive sleep apnea (OSA). We searched PubMed, Embase, and CENTRAL through August 2025 for randomised trials of CPAP, exenatide, liraglutide, tirzepatide, or their combinations. The primary endpoint was apnea-hypopnea index (AHI). Secondary endpoints were Epworth Sleepiness Scale (ESS), body mass index (BMI), systolic and diastolic blood pressure (SBP, DBP), fasting glucose, and glycated haemoglobin (HbA1c). Random-effects network meta-analyses estimated mean differences (MDs) with 95% confidence intervals (CIs). Treatments were ranked using SUCRA, and certainty of evidence was assessed with GRADE. Thirty-four trials including 3964 participants were eligible. CPAP produced the largest reduction in AHI versus no active intervention (MD -22.17 events/h; 95% CI -38.01 to -6.33) and improved ESS (MD -2.75; 95% CI -3.71 to -1.79). Liraglutide reduced BMI (MD -1.60 kg/m2; 95% CI -2.04 to -1.16) and HbA1c (MD -0.19%; 95% CI -0.25 to -0.13), whereas CPAP showed no meaningful metabolic effect. Liraglutide plus CPAP achieved the greatest BMI reduction (MD -2.00 kg/m2; 95% CI -3.49 to -0.51). No intervention significantly changed SBP, DBP, or fasting glucose. According to GRADE, certainty of evidence was moderate for CPAP effects on respiratory and sleepiness outcomes and for GLP-1 receptor agonists on BMI and HbA1c, and low for blood pressure and fasting glucose. CPAP is the most effective therapy for respiratory control, while GLP-1 receptor agonists primarily improve weight and glycaemic indices, supporting an integrated airway-metabolic approach to OSA management.

Effect of different types of exercise interventions on cardiometabolic risk factors: An umbrella review of systematic reviews and meta-analyses.

To compare the clinical efficacy and safety of intra-aortic balloon pump (IABP) and levosimendan in coronary artery bypass grafting (CABG). A systematic search of PubMed®, Embase, Cochrane Library, and Google Scholar was conducted through July 2024. Outcomes analyzed included atrial fibrillation, postoperative mediastinitis, the requirement for inotropic support, in-hospital mortality, postoperative intensive care unit (ICU) stay, postoperative length of stay, ventilation time, and mean arterial pressure (MAP) levels. The analysis included nine studies with 681 patients. Levosimendan presented advantage over IABP in CABG patients in terms of postoperative ICU stay, postoperative length of stay, and reduction in MAP levels, with effect sizes: mean difference (MD) = -0.83, 95% confidence interval (CI) -0.97 to -0.68, P < 0.00001, MD = -1.14, 95% CI: -1.33 to -0.95, P < 0.00001, and MD = -4.55, 95% CI: -6.14 to -2.96, P < 0.00001, respectively. Levosimendan had an advantage on subgroup analyses in terms of postoperative ICU stay and postoperative length of stay, with effect sizes: MD = -0.83, 95% CI: -0.93 to -0.72, P < 0.00001 and MD = -1.14, 95% CI: -1.28 to -1.01, P < 0.00001, respectively. However, the incidence of postoperative mediastinitis was higher in the levosimendan group (relative risk = 1.45, 95% CI: 0.88 to 2.38), though not statistically significant. Levosimendan may improve recovery and hemodynamic outcomes in high-risk CABG patients compared to IABP but may be associated with a higher, though non-significant, risk of mediastinitis. Further high-quality studies are warranted.

To determine the efficacy of functional training on cardiorespiratory fitness in individuals with cerebral palsy (CP). Randomized controlled trials involving individuals with CP who had functional training interventions, which also reported cardiorespiratory fitness outcomes, were included in this systematic review. Two independent reviewers searched PubMed, MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL up to February 2025, and selected studies and extracted data. Study quality was assessed using the Cochrane Risk of Bias 2 tool. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. Mean differences and standard mean differences with 95% confidence intervals (CIs) were calculated. From 594 papers, 11 randomized controlled trials (n=387, mean ages 5 years 10 months-20 years 6 months, Gross Motor Function Classification Systems levels I-IV) were included. Functional training had statistically and clinically significant effects on the 6-minute walk test (mean difference=30.91; 95% CI=28.34-33.48; p < 0.001) and Physiological Cost Index (mean difference=-0.16; 95% CI=-0.20 to -0.13; p < 0.001). No effect was found for gait speed or the timed stair test. Functional training has the potential to improve functional exercise capacity in individuals with CP. Given the significant impact of cardiorespiratory problems on the morbidity and mortality of individuals with CP, integrating cardiorespiratory parameters into functional training programmes may contribute to long-term health benefits.

Adalimumab, Anakinra, and Tocilizumab in Patients With Noninfectious Uveitis: A Multicenter Randomized Controlled Trial.

Laparoscopic transabdominal preperitoneal (TAPP) versus open Lichtenstein primary unilateral inguinal hernia repair: A systematic review and meta-analysis of randomized controlled trials.

Postoperative outcomes associated with preoperative oral hygiene in elective surgery: a systematic review and meta-analysis.

This systematic review aimed to evaluate current evidence according to toothpastes containing different active ingredients for the management of root caries in laboratory-based, in situ and clinical studies. This systematic review was conducted in accordance with Cochrane guidelines. Literature searches were performed across nine databases (up to 31.01.2024). In vitro and in situ studies were evaluated using a quality assessment tool. The Cochrane risk of bias tool (RoB2.0) was employed to assess the included clinical studies. Two reviewers independently conducted study selection, data extraction, risk of bias assessment, and certainty of evidence evaluation using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Thirteen in vitro, three in situ and 12 clinical studies were reported to meet the eligibility criteria. Mean differences (MD) were calculated for the lesion depth, mineral loss and root caries increments. Risk ratios (RR) were calculated for changes in lesion hardness and new root carious lesions in a random effects model. Meta-analysis revealed that significant differences in root carious lesions depth (MD: -55.75; 95 % CI, -90.70 to -20.80; p = 0.002) and mineral loss (MD: -1.18; 95 % CI, -1.85 to -0.51; p = 0.0006) between toothpaste and placebo treatment. In clinical studies, the use of toothpastes containing high concentration of sodium fluoride (5000 ppm) or 1.5 % arginine plus 1450 ppm Na2PO3F, when compared with standard toothpastes containing 1450 ppm sodium fluoride appeared to be effective for hardening and reversing root carious lesions (RR: 1.60; 95 % CI: 0.92 to 2.79). The pooled estimates reported that root carious lesions became hard following the use of bioactive toothpaste (1100 ppm NaF + 1 % CaSO4 + 1.1 % NH4H2PO4) in comparison to the standard toothpastes (RR: 1.81, 95 % CI: 1.39-2.36). Within the studies identified in the systematic review, toothpaste with sodium fluoride as an active ingredient in high concentration was the most effective at reducing lesion depth, improving lesion hardness, and preventing new caries. The incorporation of bioactive components that deliver calcium and phosphate (bioactive toothpaste) and the adjunctive use of fluoride with arginine may potentially manage these lesions in comparison to the standard toothpaste containing 1450 ppm sodium fluoride which might be insufficient to arrest active root caries in high-risk patients. The use of toothpaste containing high concentration of sodium fluoride as active ingredient by prescription only can be considered as the first-line non-invasive therapy for arresting active root caries. Alternatively, over-the-counter toothpastes either containing fluoride with arginine or bioactive ingredients could potentially be an optimum option for patients who cannot tolerate or decline to use high-fluoride prescriptions.

This study aims to assess the activity of the glymphatic system in patients with neuropsychiatric systemic lupus erythematosus (NPSLE) and non-NPSLE using diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) and explore the potential correlation between the DTI-ALPS index and clinical indicators. A total of 33 non-NPSLE patients, 13 NPSLE patients, and 33 age-matched healthy controls (HC) were enrolled in this study. Clinical indicators of patients were recorded, and DTI images were obtained to determine diffusivity along the x-, y-, and z-axes at the level of the lateral ventricle body. The DTI-ALPS index was calculated, and one-way ANOVA analysis with Bonferroni post hoc tests was used to assess differences among HC, non-NPSLE, and NPSLE. Pearson or Spearman correlation analysis was applied to investigate the correlation between DTI-ALPS index and clinical indicators. According to the SLEDAI scores, 44 SLE patients (non-NPSLE, n = 31; NPSLE, n = 13) were categorized into four groups, and one-way ANOVA analysis with Bonferroni post hoc tests was used to compare the ALPS index among the four groups. Compared to the healthy control (HC) group (1.705 ± 0.167), the ALPS index in the total SLE group (1.507 ± 0.138) was significantly lower [t (77) = 3.921, P < 0.001]. Both the NPSLE group (1.550 ± 0.113, n = 33) and non-NPSLE group (1.578 ± 0.148, n = 13) exhibited significantly reduced ALPS index in comparison with the HC group. One-way ANOVA showed a significant group effect on the ALPS index [F (2,76) = 7.775, P < 0.001]. Bonferroni-corrected post hoc tests indicated that the HC group had a higher ALPS index than the non-NPSLE group [mean difference = 0.127, 95% confidence interval (CI) (0.036, 0.219), P_adj = 0.003], and higher than the NPSLE group [mean difference = 0.155, 95% CI (0.033, 0.277), P_adj = 0.008]. The NPSLE was lower than that of the non-NPSLE, but this difference was not statistically significant (P_adj = 1.000), which may be partly due to the small NPSLE sample size. And we classified total SLE patients into four grades based on their SLEDAI scores. One-way ANOVA demonstrated a significant difference in ALPS index among the four SLEDAI grades [F (3, 40) = 3.210, P = 0.033]. After Bonferroni correction, only the difference between Grade 1 and Grade 3 remained significant (P_adj = 0.029); all other comparisons were not significant. Addition, no significant correlations were found between DTI-ALPS index and various clinical indicators, including serum C3, C4, CH50, anti-Smith antibodies, and SLEDAI scores. The DTI-ALPS index can serve as a noninvasive imaging biomarker for assessing glymphatic system function in non-NPSLE and NPSLE patients. These findings contribute to a better understanding of the pathophysiological mechanisms of SLE. Key Points • The pathological mechanism of SLE may be related to functional impairment of the glymphatic system. • DTI-ALPS index may serve as an MR biomarker for SLE patients.

We conducted a systematic review and meta-analysis to compare continuous ketamine infusion to other analgosedatives in critically ill children receiving invasive mechanical ventilation (IMV). We searched four electronic databases and trial registries to September 1, 2025. We searched published conference abstracts from two major critical care conferences (2022 to 2025). We preregistered the protocol on PROSPERO (CRD42025631768). Reviewers screened abstracts and full texts independently and in duplicate. We included randomized controlled trials (RCTs) and nonrandomized studies comparing ketamine to other analgosedatives in critically ill children receiving IMV. Independently and in duplicate, we conducted data extraction. We assessed risk of bias using the Risk Of Bias instrument for Use in SysTematic reviews for RCTs or Risk Of Bias In Nonrandomized Studies of Interventions tool, and certainty of evidence using Grading of Recommendations, Assessment, Development, and Evaluation. We pooled data using random-effects models. We included three RCTs and five nonrandomized studies (n = 1436 participants). Pooled analysis demonstrated that ketamine may have no effect on IMV duration (mean difference, 0.00 d; 95% CI, 0.03 d fewer to 0.03 d more; low certainty) and may reduce opioid exposure (mean difference, -8.88 µg/kg cumulative fentanyl equivalents; 95% CI, -6.99 to -10.77; low certainty). We found an uncertain effect of ketamine on delirium, withdrawal, length of stay, clinically important hypotension, and mortality compared with other analgosedatives. Long-term outcomes were not measured in included studies. There is a paucity of studies examining ketamine analgosedation in children receiving IMV, yielding mostly very low certainty evidence for patient-important outcomes due to imprecision and issues related to serious risk of bias of included studies. Methodologically rigorous RCTs are needed to better understand the potential role of ketamine analgosedation in the PICU.

Evidence-based management strategies for adult trigger digits: a systematic review and network meta-analysis of randomized controlled trials.

Men's exposure to ambient air pollution and in vitro fertilization outcomes among an infertility treatment population.

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver condition and a major cause of cirrhosis, hepatocellular carcinoma, and liver transplantation. Resmetirom, a thyroid hormone receptor β agonist, and Efruxifermin, a fibroblast growth factor 21 analogue, have shown promise in improving hepatic fat fraction (HFF) and liver enzyme levels. This study systematically compares the efficacy and safety of Resmetirom and Efruxifermin in treating MASH. A systematic search of PubMed, Cochrane, and Scopus identified 211 studies, of which eight randomized controlled trials (RCTs) were included. Primary outcomes included reductions in liver enzyme levels. Secondary outcomes assessed HFF measured by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF), as well as lipid profiles. Safety outcomes consist of serious adverse events and events leading to treatment discontinuation. Efruxifermin was associated with significant improvement in MRI-PDFF with an mean difference (MD) of -62.83% (95% CI: -72.30 to -53.36, p = 0.00), followed by Resmetirom with an MD of -37.15% (95% CI: -44.43 to -29.88, p = 0.00), additionally Efruxifermin was associated with significant reduction in aspartate transferase (AST) level, with an MD of -14.32 (95% CI: -23.92 to -4.72, p = 0.003), compared to Resmetirom (MD: -2.81; 95% CI: -12.40 to 6.79, p = 0.56). For lipid profiles, Efruxifermin showed a significant reduction in triglyceride levels with an MD of -36.95 (95% CI: -52.67 to -21.24, p = 0), while Resmetirom had an MD of -24.72 (95% CI: -33.31 to -16.14, p = 0.00). Efruxifermin demonstrated a slightly greater effect on MRI-PDFF and AST, along with more favourable safety outcomes.

Impact of having pulmonary embolism response team (PERT) on outcome of pulmonary embolism: A systematic review and meta-analysis.

Use of 940nm diode laser irradiation on conventional and cerium oxide-reinforced orthodontic adhesive before light-activated polymerization on the degree of conversion, and adhesive strength of orthodontic brackets. A scanning Electron microscope assessment.

This study aimed to summarize evidence on peripheral nerve enlargement in patients with diabetes, with and without diabetic sensorimotor polyneuropathy (DSP), compared with healthy controls. PubMed and Embase were systematically searched for ultrasound studies measuring the cross-sectional area (CSA) of peripheral nerves in patients with diabetes with and without DSP. The primary outcome was the weighted inter-group mean difference in CSA at all reported upper- and lower extremity sites. Forty-seven studies were identified, of which 41 were included in the meta-analyses. Patients with diabetes without DSP showed significantly larger CSA values than healthy controls at 3 of 11 anatomical locations, all located in the lower extremity. Patients with diabetes and DSP demonstrated increased CSA compared with controls at 9 of 14 sites, particularly at distal compression sites of the median and tibial nerves. Compared with patients with diabetes without DSP, those with DSP had significantly larger CSA values at 14 of 21 sites, with the greatest difference observed 4-5cm proximal to the medial malleolus (pooled mean difference+5.26mm2, 95% CI 0.94-9.57). In conclusion, peripheral nerve CSA is increased in diabetes and further enlarged in the presence of DSP, with the largest effects at distal compression sites.