Nevin Manimala

J Orthop Surg Res. 2025 Oct 8;20(1):883. doi: 10.1186/s13018-025-06300-2.

ABSTRACT

BACKGROUND: This study evaluates the effects of exenatide (EXE), a glucagon-like peptide-1 (GLP-1) receptor agonist, on bone healing in rats using a single radius cortical defect model and histopathological, biochemical, and in silico methods.

METHODS: Forty-two male Sprague-Dawley rats, excluding controls, were divided into 7 groups after receiving a standard radius defect. The serum levels of total protein (TP), calcium (Ca²⁺), phosphorus (P), alkaline phosphatase (ALP), osteocalcin (OC), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in each specimen were measured. Radius samples were examined histopathologically using hematoxylin and eosin (H&E) and Masson’s trichrome staining. Molecular docking analyses were used to assess EXE interactions with the GLP-1 receptor and osteogenic transcription factors. Statistical significance was set at p < 0.05.

RESULTS: Changes in the selected serum markers were observed in the blood samples obtained from the specimens; however, these changes may not have been due to EXE administration. No significant negative effect on bone healing was observed in the groups that received subcutaneous EXE after the bone defect was created. By contrast, it was observed that for the treatment group that received EXE for 7 consecutive days before the bone defect was created on Day 7, bone healing progressed more slowly than in the groups treated with saline. Regarding the binding of EXE to the other target receptors, root mean square deviation (RMSD) values were low, bruised surface area (BSA) was high, and electrostatic interactions were strong, indicating that the ligand (i.e., EXE) binds to the selected receptor surfaces.

CONCLUSION: Although the data obtained from the in vitro analyses in this study were verified using molecular docking, it should be noted that its design is preclinical. Given the widespread clinical use of GLP-1 receptor agonists in the management of type 2 diabetes mellitus (T2DM), our research findings may have translational relevance. Although derived from an experimental animal model, these results suggest that GLP-1 agonists such as EXE can exert additional effects on bone healing and inflammatory processes, thus warranting further studies, including controlled clinical investigations, to elucidate the potential implications for patient care.

PMID:41063270 | DOI:10.1186/s13018-025-06300-2

BMC Med. 2025 Oct 8;23(1):543. doi: 10.1186/s12916-025-04318-1.

ABSTRACT

BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by dysregulated interferon (IFN) signaling. Despite its importance, a comprehensive and systematic synthesis of available data is lacking and findings across studies have been inconsistent. To address this gap, a systematic review and meta-analysis was conducted to evaluate global variations in IFNα, IFN-γ, and some important cytokines in adult SLE cases compared to healthy controls (HCs). Furthermore, we assessed their association with disease activity and effect of detection methods, sample types, and regional variations.

METHODS: A systematic search was conducted in PubMed and Scopus as primary databases, with Google Scholar used as a supplementary search engine, using MeSH terms and keywords related to SLE and IFNs (up to 15 November 2024). The Quantitative synthesis was performed using Comprehensive Meta-Analysis, calculating standardized mean differences (SMD) with 95% confidence intervals (CI) using a random-effects model for continuous outcomes. Correlation data were analyzed using Fisher’s z transformation. Publication bias was accessed using funnel plots and Egger’s test. For heterogeneity, Cochrane’s Q test, I² statistic, subgroup analyses, sensitivity analyses, and Bayesian meta-analysis were conducted.

RESULTS: A total of 33 eligible studies, comparing IFN levels among 2307 SLE patients and 1599 HCs were included. Significantly elevated levels of IFNα (SMD = 1.428, 95%CI [0.78, 2.08], p < 0.001) and IFNγ (SMD = 0.922, 95%CI [0.32, 1.52], p = 0.003) in SLE patients compared with HCs were observed. Elevated levels of IFNγ were correlated with disease activity (SMD = 0.609, 95%CI [0.30, 0.91], p < 0.001). Additionally, significantly elevated levels of key pro-inflammatory cytokines, including IL-6 (SMD = 0.679, 95%CI [0.45, 0.90], p < 0.001) and TNFα (SMD = 1.754, 95%CI [0.25, 3.26], p = 0.022), were observed. Subgroup analyses revealed that differences in detection method, sample type, and geographic regions could influence measured cytokine levels.

CONCLUSIONS: The elevated IFN levels in SLE patients, with a significant correlation of IFNγ with disease activity, suggest their role in disease pathogenesis and potential as a biomarker for monitoring disease activity. The findings identify IFNs and key pro-inflammatory cytokines as potential therapeutic targets. Given the limitations of our study, future research employing robust study designs and methodologies are warranted to increase the reliability of our findings.

TRIAL REGISTRATION: PROSPERO CRD42023445357.

PMID:41063268 | DOI:10.1186/s12916-025-04318-1

AIDS Res Ther. 2025 Oct 8;22(1):100. doi: 10.1186/s12981-025-00765-1.

ABSTRACT

BACKGROUND: While non-disclosure of HIV status may protect people living with HIV (PLWH) against stigma, discrimination, and violence, disclosure may facilitate access to social support and improve treatment adherence. This study examined factors associated with non-disclosure among recently-diagnosed PLWH at IeDEA study sites in Cameroon.

METHODS: We conducted a cross-sectional study of adults ≥ 19 years newly enrolling in HIV care at three Cameroon hospitals from January 2016 to June 2023 with recent (< 1 year) diagnoses and no evidence of prior HIV care. We used logistic regression to identify factors associated with non-disclosure of HIV status at the time of enrolment.

RESULTS: Among 2880 participants, the overall prevalence of HIV status non-disclosure at enrolment was 34.4%, ranging from 48.0% among those enrolling on the day of diagnosis to 18.7% among those enrolling > 30 days after diagnosis. Men and single participants had higher odds of non-disclosure compared with women (aOR: 1.68; 95% CI 1.38, 2.04) and those who were married/living with a partner (aOR: 1.66; 95% CI 1.36, 2.02). Those with early-stage HIV disease (WHO Stage 1 or 2 or CD4 ≥ 200 cells/mm³) also had higher odds of non-disclosure (aOR: 1.48; 95% CI 1.20, 1.83) compared with participants with advanced-stage disease.

CONCLUSION: Among those diagnosed with HIV within 1 year prior to enrolment, men, single/unmarried people, and those with early-stage HIV disease were less likely to disclose their status. Further research on barriers to status disclosure among these groups is needed to guide disclosure support and counselling interventions.

PMID:41063261 | DOI:10.1186/s12981-025-00765-1

Epigenetics Chromatin. 2025 Oct 8;18(1):66. doi: 10.1186/s13072-025-00630-5.

ABSTRACT

Environmental changes can induce epigenetic modifications, influencing gene expression, phenotype, and species adaptation. This study investigates how temperature affects genome-wide DNA methylation patterns, particularly in genes crucial for sex development and whether these modifications can be transmitted across generations. Using the European sea bass -a fish model with both genetic and environmental sex determination- we analyzed DNA methylation at single nucleotide resolution using reduced representation bisulfite sequencing in 64 individuals from five families across two generations (F0 and F1). Parental fish (F0) were exposed to either control (16 °C, C) or elevated (21 °C, T) temperatures from 12 to 60 days post-fertilization. Their offspring (F1) were then subjected to four thermal regimes: control (CC), ancestral exposure via sires (TC), developmental exposure in offspring (CT), and dual exposure (TT). We determined the length of differentially methylated regions (DMRs) using a conservative, reproducible, and species-specific method adapted from plant epigenetics. To disentangle ancestral and developmental temperature effects, DMRs were classified according to their association with F0, F1, or F0 x F1 interaction effects. This allowed us to quantify the relative contribution of each treatment, separately for testes and ovaries in the F1 generation. While the proportion of additive DMRs showing cumulative temperature effects (e.g., 2.1% in testes, 1.4% in ovaries) was relatively rare, a substantial proportion of DMRs (37% in testes, 31.1% in ovaries), exhibited opposing methylation changes with F0 and F1 treatments, indicative of compensatory epigenetic interactions. These interactions were also reflected at the phenotypic level: TT individuals showed body weights comparable to CC, and the sex ratio in TT approached statistical significance when compared to CC (P = 0.051), suggesting a link between epigenetic regulation and phenotypic plasticity under elevated temperatures. Finally, we also investigated the inheritance of epimarks from sires to offspring. While most epimarks remained stable across generations, ~ 5% of all DMRs were both temperature-induced and inherited, offering direct evidence for environmentally responsive multigenerational epigenetic inheritance. This study demonstrates the role of temperature in shaping the epigenome and highlights the potential of epigenetic plasticity and inheritance in species adaptation and conservation amid global warming.

PMID:41063260 | DOI:10.1186/s13072-025-00630-5

J Orthop Surg Res. 2025 Oct 8;20(1):872. doi: 10.1186/s13018-025-06298-7.

ABSTRACT

OBJECTIVE: Neglected acetabular fractures, defined as those not addressed surgically within three weeks of injury, pose significant technical and prognostic challenges due to chronic displacement, malunion, and soft tissue contracture. This study aimed to evaluate radiological and functional outcomes of open reduction and internal fixation (ORIF) in a large prospective cohort managed at a tertiary trauma center.

METHODS: Between 2009 and 2019, patients aged 14 years and older with displaced, neglected acetabular fractures (> 3 weeks post-injury) were enrolled at a high-volume Level I pelvic trauma center. Exclusion criteria included pathological fractures, fresh fractures, unreconstructable articular surfaces, and patients who did not complete the minimum follow-up period. Of the total cohort, 94 patients underwent ORIF and were analyzed. Preoperative evaluation included CT imaging, and fractures were classified using the Letournel-Judet system. Radiological reduction quality was graded by Matta’s criteria, and functional recovery was assessed using the modified Merle d’Aubigné-Postel score. Secondary outcomes included complication rates and conversion to THA. For subgroup analysis, patients were stratified into early-late presenters (3-5 weeks) and very-late presenters (> 5 weeks). Statistical analysis employed chi-square tests for categorical variables, Student’s t-test or Mann-Whitney U test for continuous variables, and multivariate logistic regression to identify predictors of outcome, with significance set at p < 0.05.

RESULTS: Among the 94 patients analyzed, anatomical reduction (≤ 1 mm displacement) was achieved in 59.6%, with imperfect and poor reductions in 26.6% and 13.8%, respectively. Quality of reduction (β = 0.44, p < 0.001) and surgical delay (β = – 0.32, p = 0.006) independently predicted functional outcome, while fracture type and femoral head condition were not significant.On subgroup comparison, early-late presenters (3-5 weeks) showed a trend toward better outcomes compared with very-late presenters (> 5 weeks), although differences did not reach statistical significance. Major complications included heterotopic ossification (12.8%), post-traumatic arthritis (14.9%), avascular necrosis (9.6%), and conversion to THA during follow-up (10.6%).

CONCLUSION: This study represents one of the largest prospective series on neglected acetabular fractures with midterm follow-up. Despite delayed presentation, ORIF achieved satisfactory anatomical and functional results in most cases. Early surgical intervention within the neglected window was associated with superior outcomes, while subgroup analysis highlighted a gradual adverse effect of increasing delay. These findings underscore the importance of individualized surgical strategies, meticulous planning, and experienced surgical execution in optimizing results for this challenging patient population.

PMID:41063253 | DOI:10.1186/s13018-025-06298-7

World J Surg Oncol. 2025 Oct 8;23(1):360. doi: 10.1186/s12957-025-04021-8.

ABSTRACT

BACKGROUND: Preoperative localization of pulmonary nodules is crucial for sublobar resection under thoracoscopy; however, controversy persists over the optimal localization method in terms of accuracy and safety. This study evaluates a novel technique integrating indocyanine green (ICG) with medical adhesive for pulmonary nodule localization.

MATERIALS AND METHODS: In this single-center retrospective cohort, 168 consecutive patients (188 pulmonary nodules ≤ 2 cm) undergoing preoperative localization followed by uniportal thoracoscopic resection (July 2023 to June 2024) were divided into two groups: ICG combined with medical adhesive group (n = 86) versus medical adhesive group (n = 82). Localization outcomes, related complications, surgical and pathological outcomes were compared between the two groups.

RESULTS: There were no deaths or serious complications. All nodules were successfully resected thoracoscopically. The combined group demonstrated a shorter operative duration than the medical adhesive group (46.3 ± 6.7 min vs. 53.1 ± 5.9 min, P < 0.001). No statistically significant differences were identified in surgical type, length of stay, duration of drain tube retention, and total postoperative drainage volume between the two groups (P > 0.05).

CONCLUSION: The combined use of ICG and medical adhesive for preoperative localization in uniportal thoracoscopic sublobar resection of small pulmonary nodules reduces operative time compared with medical adhesive positioning and demonstrates favorable safety profiles.

PMID:41063249 | DOI:10.1186/s12957-025-04021-8

Nutr Metab (Lond). 2025 Oct 8;22(1):116. doi: 10.1186/s12986-025-01003-1.

ABSTRACT

BACKGROUND: Although nutritional support is crucial in intensive care, the impact of protein intake remains unclear, emphasizing the need for further randomized controlled trials. This study aimed to evaluate the effects of high-protein versus conventional-protein nutritional support on clinical outcomes in critically ill patients, with 60-day mortality as the primary endpoint.

METHOD: In this double-blind, two-arm, parallel-group randomized controlled trial, 56 adult patients admitted to the intensive care unit [1] were enrolled. Participants received either high-protein support (2.2 g/kg/day, actual body weight [ABW]) or conventional-protein support (1.0 g/kg/day, ABW) for 12 days. Both groups targeted 25 kcal/kg/day energy intake. Patients and data analysts were blinded. Mortality was assessed at ICU discharge, on days 28 and 60, and at hospital discharge. Hospital mortality was defined as any death occurring during the hospital stay, including both the ICU and post-ICU periods. Mid-arm circumference (MAC) was measured as an indicator of muscle attenuation.

RESULTS: Mean protein intake was 1.67 ± 0.33 vs. 0.93 ± 0.10 g/kg/day in high- vs. conventional-protein groups (P < 0.05). In-hospital mortality was significantly lower in the high-protein group (8 patients [28.6%]) compared to the conventional-protein group (16 patients [57.1%]; adjusted P = 0.049). Although 60-day mortality was also lower in the high-protein group (28.6% vs. 53.6%), the difference did not reach statistical significance (adjusted P = 0.07). A significant reduction in MAC attenuation was observed in the high-protein group (P < 0.001).

CONCLUSION: High-protein intake (1.67 g/kg/day) significantly reduced in-hospital mortality and improved preservation of muscle mass. Although 60-day mortality reduction was not significant, the trend suggests a meaningful benefit warranting further study.

IRCT REGISTRATION ID: IRCT20180619040151N4.

PMID:41063248 | DOI:10.1186/s12986-025-01003-1

Int J Equity Health. 2025 Oct 8;24(1):256. doi: 10.1186/s12939-025-02619-8.

ABSTRACT

BACKGROUND: Conflict-related sexual violence (CRSV) remains a critical public health and human rights issue across Africa, affecting vulnerable populations including women, children, and marginalized groups. This study explores the patterns and dynamics of CRSV across 54 African countries between 2020 and 2024.

METHODS: Secondary, de-identified data were sourced from the Global Health Data Exchange (GHDx). Descriptive statistics were conducted using IBM SPSS v27 to determine the trends in types of sexual violence and perpetrators. Pearson’s chi-square (χ²) and Fisher-Freeman-Halton tests were used to assess associations between variables. Count data panel regression using Stata 15 was applied to examine factors associated with both the frequency and mortality outcomes of CRSV.

RESULTS: Rape was the most prevalent form of sexual violence reported across the study period. Militants and national military forces were identified as leading perpetrators. Significant associations were found between types of sexual violence and perpetrator categories (χ²=208.209, p < 0.05), as well as between violence type and victim status (χ²=11.351, p = 0.040). Regression results revealed that perpetrators such as civilians (β = 0.897) and militants (β = 0.610) were more likely to be involved in multi-victim incidents. Sexual violence involving civilians was significantly associated with increased deaths (β = 1.342).

CONCLUSION: CRSV in Africa is widespread and patterned by conflict dynamics and perpetrator type. These findings call for the strengthening of survivor-centered policy responses, improved data systems, and legal accountability mechanisms to address CRSV as a barrier to peace and development.

PMID:41063245 | DOI:10.1186/s12939-025-02619-8

BMC Med Ethics. 2025 Oct 8;26(1):129. doi: 10.1186/s12910-025-01296-0.

ABSTRACT

The EU Clinical Trials Regulation (CTR) was introduced to harmonize clinical trial evaluations across Member States while upholding participant protection and ethical integrity. This study analyzes 6740 Requests for Information (RFIs) issued by Belgian Medical Research Ethics Committees (MRECs) across 266 trial dossiers evaluated between 2017 and 2024, spanning both the CTR pilot phase and the initial CTIS implementation. Using framework content analysis, we examined the number and content of RFIs in relation to trial outcomes, sponsor type (commercial vs. non-commercial), and the MREC’s role as Reporting Member State (RMS) or Member State Concerned (MSC).Results show a decline in total RFIs over time, mainly due to a reduction in typographical and linguistic remarks, yet significant variability persists in the formulation and scope of ethical feedback. While statistical and methodological concerns remained central in Part I evaluations, RFIs increasingly addressed newer challenges such as decentralized trials, e-consent, and data collection on ethnicity. Part II RFIs continued to focus heavily on informed consent documents. We further observed that MSCs raised fewer RFIs than RMSs for Part I, prompting reflection on the necessity and efficiency of full multi-state review in this section.The study also highlights a growing emphasis on regulatory compliance-sometimes at the expense of ethical deliberation-and the limited authority of policy advisors to correct inconsistencies, despite their expertise. We recommend clearer guidance, formalized roles for policy advisors in quality control, improved pre-submission processes, and limited direct communication between MRECs and sponsors. These findings support ongoing efforts to improve ethics review efficiency and quality under the CTR, with broader relevance for harmonization across Europe.

PMID:41063237 | DOI:10.1186/s12910-025-01296-0

AIDS Res Ther. 2025 Oct 8;22(1):101. doi: 10.1186/s12981-025-00753-5.

ABSTRACT

This study examines the prevalence of Human immunodeficiency virus (HIV) in Mizoram, Northeast India, with a focus on age-group transmission routes and gender-specific prevalence. According to data from the ART Plus Centre at Civil Hospital Aizawl (January-December 2023), men were more likely to be infected with HIV, with the 26-35 age group being the most affected. Heterosexual transmission and intravenous drug use (IDU) were shown to be the most common modes of transmission. Gender and age variations were identified by statistical analysis using SPSS^® (V 27.0), highlighting the need for focused interventions. To effectively combat the HIV epidemic in this area, gender-specific policies, harm reduction strategies, and stigma reduction measures are essential.

PMID:41063233 | DOI:10.1186/s12981-025-00753-5