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[Comparative analysis of comprehensive treatment outcomes in patients with chronic bacterial prostatitis with the addition of the multicomponent complex AndrOPREN].

INTRODUCTION: Type II chronic bacterial prostatitis is characterized by persistent infection, insufficient efficacy of standard therapy, and a high recurrence rate, which necessitates the search for additional treatment options. AIM: To evaluate the efficacy and safety of adding the multicomponent complex AndrOPREN to comprehensive therapy for type II chronic bacterial prostatitis. MATERIALS AND METHODS: This prospective, comparative, randomized study included 233 patients allocated to the main group (n=126) and the control group (n=107). In both groups, patients received standard therapy; men in the main group additionally received the multi-ingredient complex AndrOPREN at a dose of two capsules of No. 1 and two capsules of No. 2 daily for 1-2 months. The follow-up period was 60 days. Changes in symptoms according to the IPSS and QoL scores, urinalysis parameters, microscopy findings of expressed prostatic secretions, pathogen eradication, and biochemical safety parameters were assessed. RESULTS: Improvement was observed in both groups and was more pronounced in the main group. By day 14, the median IPSS score was 14.0 [12.0; 16.0] vs. 18.0 [15.0; 20.0] in the control group (p<0.001); by day 60, the corresponding values were 7.0 [5.0; 9.0] and 11.0 [9.0; 13.0] (p<0.001). At the end of follow-up, the QoL score was 2.0 [1.0; 2.0] and 3.0 [2.0; 3.0], respectively. No microbial growth was detected in 91.2% and 80.4% of patients, respectively (p=0.026); Escherichia coli eradication was achieved in 91.7% and 76.9%, respectively. No biochemical changes indicative of nephrotoxicity or hepatotoxicity were detected. DISCUSSION: The addition of the multicomponent complex AndrOPREN was associated with more rapid symptom resolution, a reduction in inflammatory changes, restoration of the secretory function of the prostate, and greater microbiological efficacy. CONCLUSION: The addition of the multicomponent complex AndrOPREN to comprehensive therapy for type II chronic bacterial prostatitis improves treatment efficacy while maintaining a favorable safety profile.

Humans

Adherence and effectiveness of multicomponent exercise fall prevention programmes across delivery formats in community-dwelling older adults: a systematic review and multilevel meta-analysis.

BACKGROUND: Multicomponent exercise is widely implemented for fall prevention in older adults, but the role of exercise adherence and delivery format in determining intervention effectiveness remains inadequately understood, particularly in analyses that account for within-study outcome dependence. METHODS: We searched five databases to 23 November 2025 for RCTs of multicomponent exercise in adults aged &#x2265;60 years. Fall outcomes were synthesised using three-level random-effects meta-analysis and meta-regression, with adherence evaluated as continuous/categorical factors and as moderator alongside delivery format, accounting for within-study effect-size dependence. RESULTS: Forty-one publications were included, comprising 36 distinct cohorts and involving 20,202 participants. Multicomponent exercise programmes significantly reduced fall incidence (IRR = 0.776, 95% CI 0.641-0.939), risk of experiencing at least one fall (RR = 0.914, 95% CI 0.858-0.974), and fall-related injury incidence (IRR = 0.754, 95% CI 0.663-0.858). Programmes achieving adherence &#x2265;75% were independently associated with greater reductions in fall incidence (IRR = 0.501, 95% CI 0.336-0.747) and fall risk (RR = 0.821, 95% CI 0.697-0.967). Mean adherence was highest in combined individual and group delivery, lower in single-format programmes, though including a group component may enhance adherence. CONCLUSIONS: Multicomponent exercise fall prevention programmes are effective for fall prevention in community-dwelling older adults, whereas evidence for their protective effects on fall-related injury outcomes remains limited. Adherence is an important factor influencing programme implementation and intervention effectiveness.

Aged

Efficacy of smartphone- and bibliotherapy-delivered multicomponent lifestyle medicine interventions for probable depression: A three-arm randomized controlled trial.

BACKGROUND: This study examined the efficacy of smartphone- (AG) and bibliotherapy-delivered (BG) lifestyle medicine (LM) interventions compared with a waitlist control group (WLG) in reducing depressive symptoms. METHODS: A total of 122 adults with probable depression were randomized to AG (n&#xa0;=&#xa0;41), BG (n&#xa0;=&#xa0;40), or WLG (n&#xa0;=&#xa0;41). AG and BG received the same core 8-week multicomponent LM intervention via a smartphone application or booklets, respectively. The core content included lifestyle psychoeducation, physical activity, diet and nutrition, stress and sleep management, goal-setting, and motivational techniques. Outcomes were assessed at baseline and immediate post-intervention (Week 9) in all groups, with 1-month (Week 13) and 3-month (Week 21) follow-ups conducted in the intervention groups only. RESULTS: At Week 9, AG (d&#xa0;=&#xa0;0.89) and BG (d&#xa0;=&#xa0;0.64) showed significantly greater reductions in depressive symptoms than WLG, with within-group improvements maintained at 1- and 3-month follow-ups (ps&#xa0;<.001, d&#xa0;=&#xa0;0.77-0.96). Clinically significant improvement was achieved by 78% of AG and 55% of BG participants, both significantly higher than WLG (19.5%; ps&#xa0;<.001). Compared with WLG, both interventions yielded greater improvements in overall lifestyle and physical activity (d&#xa0;=&#xa0;0.59-0.91) at Week 9. The AG showed additional benefits for perceived stress, health responsibility, nutrition, spiritual growth, and stress management (d&#xa0;=&#xa0;0.58-0.73), whereas BG uniquely improved insomnia symptoms (d&#xa0;=&#xa0;0.83). CONCLUSION: Smartphone- and bibliotherapy-delivered LM interventions are efficacious for managing probable depression. Further RCTs comparing them with established treatments are warranted.

Humans

Yoga MAT: A factorial randomized study using the Multiphase Optimization Strategy to develop a multicomponent yoga intervention for people with chronic pain taking medications for opioid use disorder.

BACKGROUND: People taking medications for opioid use disorder (MOUD) commonly experience chronic pain. Yoga interventions show promise for decreasing pain-related disability in other populations. More time spent in yoga practice may improve pain-related outcomes. METHODS: The Multiphase Optimization Strategy (MOST) provided the framework for developing an optimized yoga intervention package. In a 2x2x2x2 factorial experiment, we evaluated four candidate intervention components which, when added to a weekly yoga class, might increase yoga engagement. The primary outcome was minutes per week of yoga practice (classes and other yoga practice) over the 12-week intervention period. We sought to determine which combination of intervention components was associated with the most yoga practice for people with chronic pain taking buprenorphine or methadone as MOUD. RESULTS: We enrolled 192 adults. There was a significant main effect for Component "B" (having two private sessions with a yoga teachers; IRR = 1.10, 90%CI 1.02; 1.18), and a synergistic interaction between Components "B" and "D" (D was financial incentives for attending class; IRR = 1.11, 90%CI 1.02; 1.19). This combination of these two components (without other potential components) was associated with the second highest model-predicted mean minutes of yoga per week (157.1min; 90% CI = 120.1-194.0) which was only 4min less than the combination including all four components. CONCLUSIONS: We identified a combination of intervention components as the optimized intervention. A next step will be to test the effect of this optimized intervention on pain and substance use outcomes in a randomized controlled clinical trial.

Humans

Use of wearable technologies for physical activity promotion in older adults: A systematic review.

This systematic review, conducted according to PRISMA guidelines and registered in PROSPERO (CRD420251055299), examined the use of wearable technologies for promoting physical activity (PA) in adults aged 60 years and older. Searches across five databases (PubMed, Scopus, Web of Science, CINAHL, Cochrane) identified 2438 records, of which only six randomized controlled trials published between 2021 and 2025 met inclusion criteria, with sample sizes ranging from 36 to 551 participants and mean ages between 65 and 79 years. Given the small number of included studies, findings should be interpreted as preliminary. The studies ranged from the standalone use of commercial trackers (Fitbit, Polar, ActiGraph) to multicomponent interventions combining wearables with physiotherapist feedback, telephone counseling, web-based platforms, or interactive cognitive-motor training. Wearables used alone, as in the REACT trial, produced small or non-significant PA effects. In contrast, interventions integrating devices with personalized feedback, professional support, or digital platforms, such as PROMOTE and TASMANIA, were associated with more consistent improvements in PA, physical function, and cognitive outcomes. Multicomponent programs, such as PEER and ICMT, reported broader benefits, including cognition, balance, and reductions in sedentary behavior, though these findings derive from individual trials and require replication. Risk of bias, assessed with the Cochrane Risk of Bias tool version 2 (RoB 2.0), was rated as "some concerns" for five studies and low for only one, mainly due to gaps in randomization reporting, missing data, and lack of preregistration. Tentatively, and based on a very limited evidence base, wearables may have greater impact when embedded within broader behavioral systems, incorporating feedback, coaching, or interactive components, rather than when used in isolation as passive monitoring tools. Adherence and psychosocial outcomes appeared related to comfort and perceived usefulness among older adults, though larger and more robust trials are needed to confirm these patterns.

Humans

Effectiveness of tobacco cessation interventions delivered in clinical settings in South Asia: a systematic review and meta-analysis.

BACKGROUND: Despite the burden of tobacco use, access to cessation support in South Asia remains scarce. OBJECTIVE: This review evaluates the effectiveness of tobacco cessation interventions delivered in clinical settings in South Asia. METHODS: Five relevant databases were searched from inception to February 2025. Eligibility criteria included randomized and non-randomized studies evaluating behavioral, pharmacotherapy, and multicomponent interventions delivered in clinical settings in South Asia. Data on study setting and design, participant information, intervention, comparator, and outcomes were extracted. Meta-analyses using random-effect models were conducted where possible. Certainty of evidence was assessed using GRADE. RESULTS: Thirty-seven studies were included (22 randomized and 15 non-randomized). Interventions involved pharmacotherapy (n&#x2009;=&#x2009;6; 16.2%), nicotine replacement therapy (n&#x2009;=&#x2009;7; 18.9%), behavioral counseling (n&#x2009;=&#x2009;12; 32.4%), or combined/multicomponent interventions (n&#x2009;=&#x2009;12; 32.4%). Most studies were conducted in India (n&#x2009;=&#x2009;26; 70.3%), followed by Pakistan (n&#x2009;=&#x2009;6; 16.2%), Nepal (n&#x2009;=&#x2009;3; 8.1%), and two studies (5.4%) were multi-country in India, Pakistan, and Bangladesh. Pooled analyses demonstrated higher quit rates among intervention versus control for continuous abstinence at 0-3&#x2009;months (RR: 1.21, 95%CI: 1.06 to 1.37) and >3&#x2009;months (RR: 1.68, 95%CI: 1.1.4 to 2.47), and for point abstinence at >3&#x2009;months post-intervention (RR: 2.03, 95%CI:1.35 to 3.08). Heterogeneity was high for all analyses (I2 range: 94% to 97%). Combined behavioral and pharmacotherapy interventions were most effective (RR: 1.70, 95%CI: 0.98 to 2.92), although not statistically significant (p&#x2009;=&#x2009;0.06). CONCLUSION: Tobacco cessation interventions delivered in clinical settings in South Asia are effective, particularly when combining behavioral support with pharmacotherapy. However, evidence is limited by methodological weaknesses.

Humans

Effects of exercise on aerobic capacity in people with prehypertension or hypertension: a systematic review and meta-analysis of randomized controlled trials.

This study aimed to quantify the effects of exercise on aerobic capacity in people with prehypertension or hypertension and to identify exercise prescription parameters that optimize improvements. A comprehensive search was conducted in PubMed, Web of Science, Embase, Cochrane Library, and Scopus from inception to 24 October 2025. Data were pooled using standardized mean differences (SMDs) with 95% confidence intervals (CI). Fifteen studies met the inclusion criteria. Exercise significantly improved aerobic capacity in people with prehypertension or hypertension (SMD&#x200a;=&#x200a;0.88; 95% CI: 0.61-1.15; P &#x200a;<&#x200a;0.00001), with multicomponent training demonstrating superior efficacy. Exploratory subgroup analyses suggest that longer programs (&#x2265;12&#x200a;weeks), lower frequency (<3&#x200a;sessions/week), 60-min sessions or longer, total weekly exercise less than 180&#x200a;min, and professional supervision may be associated with better outcomes.

Humans

Human-Centered Workspace Optimization: A 2 &#xd7; 2 Factorial Study of Adjustable Furniture and Indoor Environmental Quality.

Small workspaces function as integrated systems, yet ergonomic furniture and indoor environmental conditions are usually evaluated separately. A six-site, assessor-blinded, randomized 2 &#xd7; 2 factorial controlled study was conducted of two multicomponent packages-adjustable furniture and optimized indoor environmental quality (IEQ)-among 240 office workers for four weeks. Each group included 60 participants. Overall comfort in week 4 was highest for both packages (5.62 &#xb1; 0.53 versus 3.99 &#xb1; 0.60 with fixed furniture and basic IEQ). In a site-adjusted factorial model with HC3 robust standard errors, the adjustable-furniture effect was 0.86 points (95% confidence interval [CI], 0.62-1.09), the optimized-IEQ effect was 0.34 points (95% CI, 0.12-0.55), and their interaction was 0.44 points (95% CI, 0.14-0.74). Adjustable furniture improved postural comfort and reduced neck and lower back discomfort; optimized IEQ improved environmental comfort; both packages improved perceived productivity, satisfaction, and fatigue. The task-accuracy interaction did not remain significant after false-discovery-rate adjustment, and exploratory mediation and spline analyses did not support indirect or nonlinear effects. These results support coordinated ergonomic and environmental implementation while preserving distinct outcome pathways.

Interior Design and Furnishings

Integrated Telehealth Rehabilitation and Quality of Life in Mechanically Ventilated Adults: A Randomized Clinical Trial.

IMPORTANCE: Whether integrated rehabilitation strategies spanning intensive care unit (ICU), hospital, and postdischarge phases improve quality of life after acute respiratory failure is uncertain. OBJECTIVE: To evaluate the effect of an integrated multicomponent telehealth-based rehabilitation intervention on health-related quality of life at 90 days after hospital discharge among adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation. DESIGN, SETTING, AND PARTICIPANTS: This stepped-wedge cluster randomized clinical trial in ICUs of 20 public hospitals in Brazil enrolled adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation between June 2024 and May 2025, with follow-up through September 2025. INTERVENTIONS: A multicomponent telehealth-based rehabilitation program integrating an ICU telehealth-based rehabilitation intervention focused on ventilator liberation; a ward telehealth-based rehabilitation intervention targeting risk stratification and initiation of individualized rehabilitation plans; and a postdischarge telehealth-based rehabilitation intervention consisting of a 2-month personalized centralized telerehabilitation program. MAIN OUTCOMES AND MEASURES: Health-related quality of life at 90 days after hospital discharge, measured using the EuroQol 5-Dimension 3-Level (EQ-5D-3L) utility score (range, -0.17 [worse than death] to 1 [best health state], with 0 representing death). RESULTS: Among 1916 enrolled patients (mean [SD] age, 60.6 [17.3] years; 43.6% female), 1063 were assigned to the intervention and 853 to usual care per local protocols. At 90 days after hospital discharge, mean (SD) EQ-5D-3L utility scores were higher in the intervention group than in the usual care group (0.16 [0.31] vs 0.12 [0.28]; adjusted difference, 0.049; 95% CI, 0.0002 to 0.098; P&#x2009;=&#x2009;.04) but did not differ among survivors (0.60 [0.32] vs 0.59 [0.32]; adjusted difference, -0.045; 95% CI, -0.138 to 0.045; P&#x2009;=&#x2009;.34). Compared with usual care, the intervention resulted in lower 90-day all-cause mortality (71.8% [676 of 941] vs 78.3% [584 of 746]; adjusted difference, -7.6%; 95% CI, -14.7% to -0.6%; P&#x2009;=&#x2009;.03) and shorter mean (SD) mechanical ventilation duration (9.9 [10.3] vs 15.5 [15.9] days; adjusted difference, -6.2 days; 95% CI, -8.5 to -3.9; P&#x2009;<&#x2009;.001). CONCLUSIONS AND RELEVANCE: In this study, an integrated telehealth-based rehabilitation strategy delivered across ICU, hospital, and postdischarge phases improved 90-day health-related quality of life, potentially influenced by reduced mortality. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06343545.

Humans

School-based sexual violence prevention: A systematic review.

PURPOSE: Sexual violence profoundly affects the health and development of children, adolescents, and young adults, representing a persistent challenge to public policy. This systematic review examined the effectiveness of school-based interventions aimed at prevention. METHODS: Eighteen randomized controlled trials published between 2012 and 2024 were retrieved from four major databases. The programs were implemented in primary, secondary, and higher education settings and targeted children, adolescents, and young adults. RESULTS: The results revealed improvements in knowledge and attitude, particularly regarding consent and awareness, whereas evidence supporting behavioral changes was less frequent and often limited. Methodological limitations, such as short follow-up periods and participant attrition, restricted the assessment of long-term outcomes. CONCLUSIONS: This review highlights the importance of multicomponent, participatory, and culturally sensitive approaches, along with the integration of digital tools and continuous evaluation systems, to strengthen the role of schools as safe and transformative spaces in the prevention of sexual violence. IMPLICATIONS AND CONTRIBUTIONS: This systematic review suggests that school-based interventions hold significant potential for the prevention of sexual violence. It identifies promising strategies and reinforces the importance of culturally sensitive, sustained, evidence-based approaches to ensure learning environments that are safe, protective, and promotive of gender equity.

Humans

BIOCARD framework: integrating fecal bile acids, lipids, and metabolites to assess response to a cardiovascular health intervention.

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality, particularly in under-resourced populations. Although nutritional interventions are important for CVD prevention, their outcomes are commonly evaluated using conventional clinical and behavioral indicators, which may not fully capture early molecular responses. In this study, we developed the BIOCARD framework, an exploratory fecal multi-omics platform integrating bile acids, lipids, and metabolites to evaluate intervention outcomes related to cardiovascular health. Fecal samples were collected from caregiver-child participants enrolled in a 10-week randomized controlled trial comparing a multicomponent garden-based intervention (SHA) with an education-only control group (MSP). Fecal polar metabolites, lipids, and bile acids were analyzed by UHPLC-HRMS-based approaches and integrated with conventional health indicators. Traditional clinical indicators in the present study showed limited sensitivity for detecting intervention-related differences. In contrast, fecal multi-omics analyzes revealed intervention-associated differences in metabolites, lipids, and bile acids, with children showing more apparent molecular variation than parents. Network analysis further revealed associations between selected molecular features and cardiovascular-related indicators, including blood pressure, body fat, skin carotenoids, and Healthy Eating Index scores. Together, these findings suggest that the BIOCARD framework may serve as an exploratory molecular approach to complement traditional outcome measures and improve the evaluation of nutritional interventions for cardiovascular health.

Humans

Predictive Validity of Violence Screening Tools in Emergency and Psychiatric Services: A Systematic Review.

Violence against healthcare staff, including a threat or an act of violence toward people during their work, poses a physical and psychological risk to workers internationally. Screening is an important strategy in preventing violence against healthcare professionals. The aim of this systematic review was to synthesize evidence on the predictive validity of risk assessment tools used to screen for violence and aggression risk toward healthcare workers in emergency and psychiatric departments (PD). Primary studies that examined the predictive validity of risk assessment tools for workplace violence were identified via a systematic search of Medline, PsycINFO, Embase, and the Cochrane databases. There were 62 eligible studies, ten of which had a lower risk of bias (RoB). Those studies with high RoB were primarily due to a failure to present calibration measures as part of the analysis. All included studies adopted a longitudinal design and were conducted in PDs. The ten highest-quality studies reported on eight different instruments, four of which showed acceptable to outstanding predictive performance. The Dynamic Appraisal of Situational Aggression and the Br&#xf8;set Violence Checklist showed the best predictive performance; they were also validated in emergency departments and are best suited for short-term risk prediction. We recommend that the selection of a risk assessment tool should consider the following: (a) the target population, (b) the violence operationalization, and (c) the purpose of the monitoring. We note that the use of a screening tool should be a part of a multicomponent strategy to ensure staff safety.

Humans

Effectiveness of peer recovery support services for substance use disorders: A systematic review of healthcare utilization, behavioral health, and engagement outcomes.

BACKGROUND: Peer recovery support services (PRS) delivered by individuals with lived experience of substance use, are increasingly incorporated into substance use disorder (SUD) care systems to improve care engagement, reduce acute care use, and support recovery. However, existing systematic reviews have focused on substance use outcomes, with limited attention to healthcare utilization, psychosocial functioning, and outcomes across settings, and populations. METHODS: This systematic review, registered in PROSPERO (CRD42023469279), synthesized peer-reviewed studies from 2003 to 2026 evaluating PRS for individuals with alcohol or drug-related SUD. Using MEDLINE, Embase, PsycINFO, and CINAHL, the review included 53 studies primarily conducted in high-income countries that reported quantitative outcomes across substance use, healthcare utilization, behavioral health, and treatment engagement. Risk of bias was assessed using Cochrane RoB 2, ROBINS-I, and ROBINS-E tools. RESULTS: Overall, evidence was most favorable for selected treatment-linkage and engagement outcomes, whereas findings for substance use, emergency department use, hospitalization, overdose, and mortality were inconsistent. Uncontrolled longitudinal studies frequently reported improvements in depression and anxiety, but no randomized trials evaluated these outcomes, limiting causal inference. Exploratory cross-study patterns suggested that sustained navigation, practical assistance, and repeated peer contact were more often present in programs reporting favorable outcomes; however, these components were not independently evaluated. Substantial heterogeneity, frequent multicomponent interventions, high risk of bias in many nonrandomized studies, and limited long-term and economic data constrain conclusions. CONCLUSIONS: Findings support the promise of PRS while underscoring the need for more rigorous comparative studies, cost-effectiveness data, and further research in low- and middle-income countries.

Humans

Structural complexity and mechanistic diversity of MECOM rearrangements in myeloid neoplasms.

Rearrangements involving MECOM at chromosome 3q26.2 are recurrent in myeloid neoplasms, classically represented by inv(3)(q21q26.2) and t(3;3)(q21;q26.2), which reposition the GATA2-distal haematopoietic enhancer and drive aberrant EVI1 overexpression. However, the full structural and mechanistic diversity of MECOM rearrangements (MECOM-r) is yet to be explored. We retrospectively analysed 97 cases with cytogenetically defined MECOM-r and identified 12 with complex rearrangements using GTG-banded karyotyping and tri-colour interphase/metaphase fluorescence in situ hybridisation analyses. These 12 cases demonstrated remarkable structural heterogeneity. The abnormalities encompassed translocations, inversions, insertions, duplications, and deletions, which often coexisted within the same specimen as multiple rearranged subclones. Insertional events emerged as a distinct mechanism of MECOM activation. These encompassed insertions of MYNN and/or MECOM into chromosomes 1 and 6, insertion of chromosome 8 segment into MECOM, and inverted insertions between homologous chromosome 3 segments. Recurrent breakpoints at 3q21 across multiple cases, together with localised copy number imbalances frequently involving the MYNN and GOLIM4 loci at 3q26.2, underscore the architectural fragility of these two regions. Co-occurring abnormalities such as -5/del(5q), -7/del(7q), and TP53 loss were common, reflecting a permissive genomic background for chromosomal reassembly. Our findings expand the mechanistic landscape of MECOM-r beyond canonical inv(3)/t(3;3), establishing 3q21 and 3q26.2 as structural 'hotspots' and genomic instability hubs. Distinct from fusion-driven oncogenes such as KMT2A, MECOM activation results from enhancer hijacking and regional structural remodelling, leading to EVI1 overexpression and clonal evolution in myeloid malignancies.

Humans

Anatomy and Biomechanics of the Deltoid Ligament Complex in Healthy Ankles: Protocol for a Systematic Review and Meta-Analysis.

INTRODUCTION: Up to one in two individuals who have a history of an ankle injury will develop chronic ankle instability, which subsequently increases the risk of osteoarthritis development. Although lateral ankle ligament injuries are the most common, recent research shows that concomitant injuries to the deltoid (medial collateral) ligament complex may be more prevalent than previously recognised. However, the anatomy and biomechanics of the deltoid ligament complex are reported inconsistently in the literature. This systematic review will summarise current evidence on the anatomy and biomechanics of the deltoid ligament complex in healthy adult ankles. METHODS: Searches will be conducted in Scopus, MEDLINE, Embase, CINAHL and SPORTDiscus. Our search strategy will cover terms associated with 'deltoid ligament', 'anatomy' and 'biomechanics'. We will only include dissection and imaging studies published in English that report any of the listed clinically relevant properties of the deltoid ligament in healthy adult human ankles. Two reviewers will independently perform screening and assess study quality using the anatomical quality assessment (AQUA) tool. One reviewer will extract relevant data, which will be independently verified by co-authors. Primary outcomes include band prevalence, length, width, cross-sectional area, maximum and/or failure load and elastic modulus. If three or more studies report a primary outcome, we will conduct a meta-analysis and report findings as pooled means with 95% confidence intervals. If a meta-analysis is not feasible, outcomes will be summarised as a narrative analysis. Measures will be taken during data synthesis to address anticipated methodological heterogeneity across included studies, and pooled estimates will be interpreted with caution. DISCUSSION: This protocol details a systematic review that aims to summarise the anatomy and biomechanics of the deltoid ligament complex. Our findings will inform computational modelling, clinical management and biomechanics for ankle pathologies, as well as identifying research gaps and directions for future research. TRIAL REGISTRATION: PROSPERO: CRD420251142867.

Humans

Diverse structures of mcr-10-bearing plasmids and high colistin resistance in Enterobacter cloacae complex clinical isolates from South Korea.

BACKGROUND: The emergence of mcr-mediated colistin resistance in Enterobacter cloacae complex (ECC) poses a significant threat to antimicrobial therapy. Among mcr variants, mcr-10 has been identified in various environments, but its genetic diversity, structural context, and functional role in colistin resistance remain unclear. METHODS: We investigated 183 ECC isolates and identified 60 colistin-resistant strains through minimum inhibitory concentration (MIC) testing. The presence of mcr-10 was screened using reference genomes from NCBI, and whole plasmid sequencing was conducted on mcr-10-positive isolates. The genetic environment of mcr-10 was analyzed via synteny and structural annotation. RESULTS: Whole-plasmid sequencing of eight mcr-10-positive ECC isolates identified three replicon types among the mcr-10-harboring plasmids: IncFIB (n=3), IncFII (n=3), and IncFII/IncFIB (n=2). Although all plasmids shared the xerC-mcr-10 cassette, they lacked a conserved backbone and showed diverse genetic contexts with variable insertion sequences near mcr-10, indicating marked structural heterogeneity. No additional antimicrobial resistance genes were detected on these plasmids. When introduced into E. coli DH5&#x3b1;, the plasmids increased colistin MICs only modestly, whereas representative plasmids transferred into colistin-susceptible E. roggenkampii and E. kobei conferred high-level resistance comparable to that of the parental mcr-10-positive isolates. Consistently, qRT-PCR showed higher mcr-10 expression in ECC transformants than in E. coli under colistin exposure, supporting a hostdependent effect on mcr-10-mediated colistin resistance. CONCLUSION: These findings highlight the diversity of mcr-10-carrying plasmids and suggest that mcr-10-mediated colistin resistance is shaped by the host genetic background. Further studies are needed to clarify the mechanisms underlying mcr-10 expression.

Colistin

Induced degradation of Ufd1 reveals regulation of cohesin by the VCP/p97Ufd1-Npl4 complex.

The AAA ATPase VCP/p97 has emerged as a critical regulator of ubiquitin and chromatin-associated processes but progress in understanding has been hampered by the complexity of p97 functions and the various p97 cofactors involved. Here, we combined ubiquitin profiling with acutely induced degradation of the Ufd1 subunit of the p97 ubiquitin adapter, Ufd1-Npl4, in human cells. We identified a set of chromatin regulators, HUS1, XRCC1, MORF4L1, and the cohesin subunit RAD21 as targets of p97Ufd1-Npl4 We find that RAD21 is ubiquitylated and targeted by p97Ufd1-Npl4 specifically in S phase to remove a subpopulation of cohesin from chromatin. Acute degradation of Ufd1 in S phase, after replication licensing is completed, impedes replication and leads to replication-associated DNA damage. Our findings suggest that a fraction of cohesin rings need to be removed by p97Ufd1-Npl4 from DNA to allow unhindered replication and reveal a critical function of p97 that ensures genome stability.

Cell Cycle Proteins

Metabolomic differences in the Ophiura sarsii complex from the Yellow Sea Cold Water Mass and Bering Sea Cold Pool.

Metabolomics provides a functional readout of cellular physiology and can reveal metabolite-level differences associated with environmental and evolutionary contexts. Here, we used GC-MS- and LC-MS-based metabolomics to characterize metabolic profiles of the Ophiura sarsii complex from the Yellow Sea Cold Water Mass (YSCWM) and the Bering Sea Cold Pool (BSCP). This metabolomics analysis identified 398 LC-MS/MS and 87 GC-MS/MS differential metabolites (DEMs). Marked metabolic differences were observed between the two taxa, involving antioxidant-related metabolites, central carbon-related intermediates, osmolyte-associated compounds, and membrane lipid components. O. sarsii vadicola from the YSCWM showed higher levels of glutathione, glucose, citric acid, D-ribulose 5-phosphate, and unsaturated lipid-related metabolites, indicating differences in antioxidant-related and energy-associated metabolic profiles. By contrast, O. sarsii from the BSCP was characterized by higher levels of sugar alcohols, particularly myo-inositol, together with differences in membrane lipid-associated metabolites. These results provide metabolomics-based evidence for metabolite-level physiological differences between two members of the O. sarsii complex sampled from the Yellow Sea Cold Water Mass and the Bering Sea Cold Pool, while the relative contributions of lineage divergence and site-specific environmental variation remain to be tested experimentally.

Metabolomics