Category: Nevin Manimala

J Neuroinflammation. 2026 Jul 17. doi: 10.1186/s12974-026-03965-2. Online ahead of print.

ABSTRACT

Persistent upregulation of the purinergic receptor P2X4R is strongly associated with microglial activation in neuropathic pain, yet the epigenetic mechanisms linking chromatin remodeling to its dysregulation remain unclear. Here, we delineate a hierarchical epigenetic cascade that promotes transcriptional activation of P2X4R in spinal microglia following nerve injury. In a mouse spared nerve injury (SNI) model, microglial activation was accompanied by increased expression of P2X4R and the histone acetyltransferase p300, together with enhanced histone acetylation (H3K9ac, H3K27ac, H4K5ac, and H4K8ac) and increased chromatin accessibility at the P2rx4 promoter. Microglia-specific deletion of p300 blunted injury-induced histone acetylation and suppressed P2X4R upregulation. We further demonstrate that the acetylation reader BRD4 is recruited to these regions and cooperates with the transcription factor SP1 to drive P2rx4 transcription, supported by chromatin analyses revealing inducible assembly of a BRD4-p300-SP1 axis. Disruption of this cascade via p300 inhibition (C646) or BRD4 blockade (JQ1) attenuated spinal neuroinflammation and alleviated nociceptive hypersensitivity. Notably, reactivation of P2X4R by BzATP largely reversed the analgesic effects of BRD4 inhibition, establishing P2X4R as a critical downstream effector. Collectively, these findings support a p300-BRD4-SP1 epigenetic cascade linking chromatin remodeling to microglia-mediated neuropathic pain, highlighting this pathway as a potential therapeutic target.

PMID:42469847 | DOI:10.1186/s12974-026-03965-2

Clin Epigenetics. 2026 Jul 17. doi: 10.1186/s13148-026-02206-w. Online ahead of print.

ABSTRACT

BACKGROUND: Global population aging underscores the urgent need for biomarkers quantifying biological aging trajectories. While DNA methylation-derived pace of aging (DunedinPoAm) measures individual differences, its generalizability across diverse populations and mechanistic links to systemic inflammation remain underexplored. This study aimed to systematically examine the longitudinal associations between the DunedinPoAm and all‑cause mortality in a multiethnic cohort, and to quantify the extent to which systemic inflammatory biomarkers mediate these associations using causal mediation analysis.

METHODS: For this cohort study, information on a nationally representative cohort of 21,004 U.S. adults was extracted from the National Health and Nutrition Examination Survey (NHANES) conducted from 1999 to 2002, along with the NHANES Linked Mortality File, which ascertained mortality through December 31, 2019. The exposures were Pace of aging (DunedinPoAm) and inflammation. The survival outcome measured was all-cause mortality. We employed Cox proportional hazards models, Kaplan-Meier survival curves, restricted cubic splines, and Bayesian mediation frameworks to evaluate mortality risk, explore non-linear dose-response relationships, and investigate inflammatory mediation.

RESULTS: Data were analyzed from 2,532 participants, with a mean follow-up duration of 18.5 ± 1.29 years. Higher DunedinPoAm quartiles exhibited graded mortality risks (Q4 vs. Q1: HR = 2.50, 95% CI 1.84-3.38), which persisted after multivariable adjustment. Restricted cubic splines revealed a non-linear association (P for overall < 0.001; P for nonlinearity < 0.001), indicating the presence of threshold effects. Systemic inflammation mediated 2.33-23.5% of the mortality risk associated with DunedinPoAm, driven by CD4 + T cells, B cells, CRP and comprehensive inflammatory indices. A significant interaction with diabetes (P for interaction = 0.026) underscored metabolic dysregulation as a vulnerability factor.

CONCLUSION: DunedinPoAm predicts all-cause mortality in a non-linearly manner across multiethnic populations, partially mediated by pathways associated with inflammaging. The observed diabetes-specific interactions and threshold effects indicate the potential for precision approaches targeting high-risk subgroups. These findings support the integration of DunedinPoAm into gerotherapeutic trials and public health strategies aimed at addressing disparities in aging.

PMID:42469841 | DOI:10.1186/s13148-026-02206-w

BMC Sports Sci Med Rehabil. 2026 Jul 17. doi: 10.1186/s13102-026-01886-4. Online ahead of print.

ABSTRACT

BACKGROUND: This study investigated the effects of static quadriceps angle (Q-angle) and body composition on dynamic landing mechanics in young female athletes.

METHODS: Twenty-four right-limb dominant female athletes (age: 17.04 ± 0.36 years, BMI: 20.65 ± 2.62) participated. Body composition was assessed via bioelectrical impedance. Static Q-angle, frontal plane projection angle (FPPA), and Landing Error Scoring System (LESS) scores during a drop vertical jump were analyzed using 120 fps cameras and Kinovea software.

RESULTS: Correlation analysis revealed significant negative relationships between right Q-angle and both right FPPA (rho = -0.440, p = .031) and left FPPA (rho = -0.490, p = .015). A significant positive correlation was found between body fat percentage and LESS scores (r = .521, p = .009). The regression model explained 22.6% of variance in right FPPA, showing a near-significant exploratory trend for right Q-angle (beta = -0.394, p = .060). ROC analysis suggested a potential, exploratory threshold value of 15.00 degrees for right Q-angle to detect high-risk landing mechanics (LESS > 6), yielding 78.6% sensitivity and 60.0% specificity, although the model did not reach formal statistical significance (p = .143).

CONCLUSIONS: While the static Q-angle demonstrates a preliminary correlation with dynamic knee valgus tendencies in the dominant limb, non-significant predictive models prevent its use as a definitive standalone screening tool at this stage. Conversely, an elevated body fat percentage independently impairs overall movement quality rather than altering specific frontal plane joint angles.

TRIAL REGISTRATION: Not applicable.

PMID:42469835 | DOI:10.1186/s13102-026-01886-4

Cardiovasc Diabetol. 2026 Jul 17. doi: 10.1186/s12933-026-03295-w. Online ahead of print.

ABSTRACT

BACKGROUND: Integrating metabolic biomarkers with anthropometric indicators has been shown to enhance the discriminative capacity for cardiovascular disease (CVD). However, the impact of the cholesterol-HDL-glucose index (CHG) and its derivatives on CVD risk remains unclear. This study aimed to investigate the associations of CHG and its derivatives with CVD and to compare their discriminative performance.

METHODS: This prospective study included 3,359 CVD-free participants from the China Health and Retirement Longitudinal Study (CHARLS). Repeated measurements obtained in 2011 and 2015 were used to derive cumulative exposure and longitudinal trajectory patterns of CHG and its derivatives. Associations of baseline values, cumulative exposure, and longitudinal trajectories of these indicators with incident CVD and stroke were examined using Cox proportional hazards regression models.

RESULTS: During a median follow-up of 5 years, 466 participants (13.9%) developed CVD. Both CHG and its derivatives were significantly associated with CVD across baseline measurements, cumulative exposure, and longitudinal trajectories. Cumulative CHG derivatives showed significantly better discriminative power than isolated cumulative CHG (Delong’s test P < 0.05), with the highest associations observed for cumulative CHG-waist circumference (HR = 1.29) and cumulative CHG-Chinese visceral adiposity index (HR = 1.28). Regarding trajectory patterns, participants with stably high CHG-CVAI exhibited the greatest risk compared with those maintaining stable low levels (HR = 1.79), followed by CHG-WC (HR = 1.65). Additionally, ascending and declining trajectories of both CHG-CVAI and CHG-WC were associated with increased CVD risk (ascending CHG-CVAI: HR = 1.79; declining CHG-CVAI: HR = 1.54; ascending CHG-WC: HR = 1.45; declining CHG-WC: HR = 1.54).

CONCLUSIONS: CHG and its derivatives were strongly associated with incident CVD, with CHG-CVAI and CHG-WC exhibiting the most pronounced associations. Moreover, ascending and declining trajectories of CHG-CVAI and CHG-WC were linked to higher risk, highlighting the importance of tracking dynamic increases while also accounting for baseline metabolic status. These indicators may facilitate the identification of individuals at elevated risk for CVD.

PMID:42469827 | DOI:10.1186/s12933-026-03295-w

Malar J. 2026 Jul 17. doi: 10.1186/s12936-026-06058-w. Online ahead of print.

ABSTRACT

BACKGROUND: Malaria remains a major cause of febrile illness in Malawi; however, the epidemiology of non-malarial febrile illnesses (NMFIs) is less well characterized. Understanding the distribution and determinants of NMFIs across demographic groups is essential for improving case management in malaria-endemic settings.

OBJECTIVES: This study aimed to characterized the distribution and predictors of NMFIs among preschool-aged children (PSC), school-aged children (SAC), women of reproductive age (WRA), and men in Malawi.

METHODS: Secondary data from the 2015-2016 Malawi Micronutrient Survey were analyzed. Multivariable logistic regression models were fitted separately for each population subgroup to identify factors independently associated with NMFIs. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were reported.

RESULTS: The prevalence of NMFIs was highest among PSC (27.0%) and lowest among men (9.1%). Asymptomatic malaria was most common in SAC (28.6%), while symptomatic malaria was highest in PSC (15.9%). Among PSC, age 24-35 months (aOR = 2.5; 95% CI 1.4-4.6), recent diarrhea (aOR = 1.6; 95% CI 1.1-2.5), recent cough (aOR = 3.8; 95% CI 2.5-5.7), wasting (aOR = 2.2; 95% CI 1.0-4.8), and urban residence (aOR = 1.9; 95% CI 1.0-3.5) were associated with increased odds of NMFIs. In SAC, WRA, and men, recent cough was a consistent predictor of NMFIs (aOR = 1.9; 95% CI 0.9-4.2; aOR = 3.1; 95% CI 1.7-5.8; and aOR = 44.3; 95% CI 10.2-192.8, respectively). Among WRA and men, elevated alpha-1-acid glycoprotein levels were also associated with higher odds of NMFIs (aOR = 2.2; 95% CI 1.0-4.8 and aOR = 4.5; 95% CI 1.0-86.4, respectively).

CONCLUSION: PSC bear the highest burden of NMFIs and symptomatic malaria, while SAC commonly harbor asymptomatic malaria. Febrile illness management should move beyond malaria-focused approaches to include integrated screening for common non-malarial infections, particularly in young children.

PMID:42469805 | DOI:10.1186/s12936-026-06058-w

BMC Oral Health. 2026 Jul 17. doi: 10.1186/s12903-026-09276-5. Online ahead of print.

ABSTRACT

BACKGROUND: Psychiatric outpatients receiving long-term psychotropic therapy are at increased risk of oral health problems because of medication-related xerostomia, impaired self-care, and reduced utilisation of dental services. This study evaluated the association between psychological distress and periodontal status, plaque accumulation, and salivary flow rate among psychiatric outpatients in Peshawar, Pakistan.

METHODS: A hospital-based analytical cross-sectional study was conducted in the psychiatric outpatient departments of tertiary care hospitals in Peshawar, Khyber Pakhtunkhwa, Pakistan. A total of 168 participants receiving psychotropic medications for at least six months were recruited through consecutive sampling. Psychological distress was assessed using the validated Depression Anxiety Stress Scale-21 (DASS-21). Clinical parameters included the Silness and Löe Plaque Index (PI), mean probing pocket depth (PPD) measured using a UNC-15 periodontal probe, and unstimulated salivary flow rate (SFR).

RESULTS: The mean age of participants was 34.7 ± 10.2 years, and 53.0% were male. Moderate to extremely severe psychological distress was observed in 64.9% of participants. The mean plaque index was 1.87 ± 0.61, the mean probing pocket depth was 3.42 ± 0.89 mm, and the mean salivary flow rate was 0.21 ± 0.09 mL/min. DASS-21 total score showed a significant positive correlation with plaque index (r = 0.47, p < 0.001) and probing pocket depth (r = 0.43, p < 0.001), while an inverse correlation was observed with salivary flow rate (r = – 0.52, p < 0.001). Multiple linear regression analysis identified DASS-21 score, plaque index, salivary flow rate, age, and duration of psychotropic medication use as independent predictors of probing pocket depth (R² = 0.48, p < 0.001).

CONCLUSION: Psychological distress was significantly associated with poorer periodontal status and reduced salivary flow among psychiatric outpatients receiving chronic psychotropic therapy. These findings highlight the importance of integrating routine oral health assessment and preventive dental care into psychiatric outpatient services, particularly in low- and middle-income country settings.

PMID:42469801 | DOI:10.1186/s12903-026-09276-5

BMC Oral Health. 2026 Jul 17. doi: 10.1186/s12903-026-09355-7. Online ahead of print.

ABSTRACT

BACKGROUND: Although smoking is a well-recognized risk indicator for peri-implantitis (PI), the association between the intensity of current smoking and PI remains insufficiently characterized. This study investigated the association between smoking exposure, categorized according to daily cigarette consumption, and PI in a survey-based cross-sectional study.

METHODS: A total of 1,021 patients with at least one functional dental implant were included. Peri-implant conditions were classified at the patient level according to the implant site showing the poorest peri-implant condition in each participant, based on standardized clinical and radiographic criteria. Smoking exposure was assessed using a self-administered questionnaire and categorized as non-smoker, former smoker, or current smoker, with current smokers further stratified as light smokers (1-9 cigarettes/day), moderate smokers (10-19 cigarettes/day), or heavy smokers (≥ 20 cigarettes/day). Logistic regression analyses were performed to estimate crude and adjusted odds ratios for PI after sequential adjustment for age, sex, periodontitis stage, diabetes mellitus, and hypertension.

RESULTS: PI was identified in 150 participants (14.7%). Moderate smokers exhibited significantly higher odds of PI (adjusted odds ratio [AOR] = 2.01; 95% confidence interval [CI], 1.13-3.59), and heavy smokers showed the highest odds (AOR = 3.57; 95% CI, 2.00-6.38). In contrast, the estimates for former smokers and light smokers were not statistically significant and should be interpreted cautiously because of the small number of PI events and wide CIs.

CONCLUSION: Higher daily cigarette consumption was associated with higher odds of PI, with significant associations observed in individuals smoking 10 or more cigarettes per day. These findings support the clinical relevance of assessing daily cigarette consumption during peri-implant risk evaluation. However, longitudinal studies are needed to confirm temporality and to further refine smoking-related risk assessment in peri-implant care.

PMID:42469796 | DOI:10.1186/s12903-026-09355-7

BMC Health Serv Res. 2026 Jul 18. doi: 10.1186/s12913-026-15094-w. Online ahead of print.

ABSTRACT

BACKGROUND: Fragmented interfaces between municipal and specialist services make integrated mental healthcare difficult, and coordination in rural settings presents unique challenges. Flexible Assertive Community Treatment (FACT) aims to reduce fragmentation through multidisciplinary, community-based care. However, evidence remains limited regarding the services rural FACT teams deliver and how integrated care is enacted in everyday practice. This study examined service distribution and the coordination practices that enable integration in a rural Norwegian FACT team.

METHODS: We used an explanatory sequential mixed-methods design. A prospective service mapping captured 2,319 patient-related contacts among 70 patients over 12 weeks and was analysed with time-weighted descriptive statistics. A subsequent focus group with team members was analysed using reflexive thematic analysis. Integration occurred by building (quantitative results informed the interview guide) and merging (interpretive integration of quantitative patterns and qualitative themes).

RESULTS: Approximately 80% of services were delivered directly by the team and 20% in collaboration with external partners. Service delivery was broadly divided between clinical contacts (one-third) and interprofessional coordination/collaboration (one-third); the remaining third comprised daily life mastery, therapeutic alliance, and social support. 28% of contacts were conducted via phone, text, or videoconference, mainly for rapid coordination. Qualitative findings identified three interrelated practices underpinning integration under rural constraints: collaborative alliance, involving trust-based partnerships with patients, families, and services; information alignment, encompassing the gathering, refinement, and communication of fragmented information to establish a shared and actionable understanding; and safety valve thinking, referring to anticipating uncertainty and maintaining contingency plans to flexibly organise care within the rural network of care.

CONCLUSION: Integrated care in rural FACT practice is enabled through extensive coordination and collaborative work, supported by relational and adaptive practices. These findings underscore the importance of context-sensitive adaptations alongside model fidelity to sustain patient safety and continuity of care.

PMID:42469790 | DOI:10.1186/s12913-026-15094-w

BMC Womens Health. 2026 Jul 17. doi: 10.1186/s12905-026-04688-5. Online ahead of print.

ABSTRACT

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a disorder commonly seen in females of reproductive age. Significant associations have been reported between oral inflammation, periodontal diseases, and PCOS. An increase in inflammatory markers may be a factor for quality of life in patients with PCOS.

OBJECTIVES: The aim of this study was to evaluate the relationship between xerostomia and oral health-related quality of life in females with PCOS.

METHODS: In face-to-face interviews, patients diagnosed with PCOS and a healthy control group completed a questionnaire including demographic data, the Oral Health Impact Profile (OHIP-14) and the Xerostomia Inventory. The data obtained were analyzed statistically in the IBM SPSS vn. 27 program.

RESULTS: The OHIP-14 total points and the xerostomia points were determined to be statistically significantly higher in the PCOS group than in the control group (p < 0.05). A positive, moderate-level correlation was seen between the OHIP-14 total points and the xerostomia points (p < 0.05).

CONCLUSION: The study results showed that xerostomia was associated with PCOS and the oral health-related quality of life was affected in these patients. In females diagnosed with PCOS, keeping oral health under control can improve quality of life. It highlights the importance of integrating routine oral health assessments into the standard clinical management of women with PCOS. Healthcare professionals should adopt a multidisciplinary approach to identify and manage oral health problems that could adversely affect patients’ quality of life.

PMID:42469787 | DOI:10.1186/s12905-026-04688-5

BMC Med Inform Decis Mak. 2026 Jul 17. doi: 10.1186/s12911-026-03665-0. Online ahead of print.

ABSTRACT

BACKGROUND: Parkinson’s disease is a rapidly growing neurodegenerative disorder with various motor and non-motor symptoms, affecting millions of people worldwide. These symptoms demonstrate significant medication-related fluctuations and inter-patient variability, highlighting the need for personalized management. Objective longitudinal symptom monitoring through wearable sensors and machine learning can support individualized care. However, to date, most approaches have been tested in lab-constrained environments. This study aims to develop a modular pipeline to automatically detect three cardinal Parkinson’s disease motor symptoms, tremor, bradykinesia, and levodopa-induced dyskinesia in more realistic scenarios.

METHODS: The proposed approach was evaluated on three datasets: the Levodopa Response Study and two newly introduced ALAMEDA datasets, containing tri-axial wrist accelerometer data collected with commercial wearable devices during clinical assessments and activities of daily living. For each symptom, separate context-agnostic models were developed using 92 hand-crafted features. Multiple segmentation window lengths and preprocessing techniques, including resampling and dimensionality reduction, alongside various machine learning models, including logistic regression, k-nearest neighbor, multilayer perceptron, support vector machine, decision tree, AdaBoost, and random forest, were explored. Statistical significance between configurations was assessed with the Wilcoxon signed-rank test. Model interpretability was investigated using Shapley additive explanations to identify highly influential predictors and assess their physiological relevance.

RESULTS: In the Levodopa Response Study dataset, tremor, bradykinesia, and dyskinesia detection reached 0.664, 0.636, and 0.443 area under the precision-recall curve, respectively, demonstrating scalability in high-complexity settings and revealing physiologically meaningful patterns. When evaluated on the ALAMEDA datasets, tremor and dyskinesia detection achieved 0.879 and 0.648 area under the precision-recall curve, highlighting strong model and feature generalizability. Across symptoms, longer segmentation windows and random forest classifiers performed better, while synthetic oversampling and principal component analysis showed limited impact.

CONCLUSIONS: Automated Parkinson’s disease symptom detection is feasible in more realistic, free-living conditions, with only a slight performance decrease despite substantially increased complexity. With carefully selected features and pipeline components, the objective, unobtrusive monitoring of motor symptoms can support personalized, evidence-based treatment suggestions, eventually improving patients’ quality of life.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:42469783 | DOI:10.1186/s12911-026-03665-0