Nevin Manimala

Implement Sci. 2026 Jul 17. doi: 10.1186/s13012-026-01528-w. Online ahead of print.

ABSTRACT

BACKGROUND: The treatment of depression is essential for improving both psychiatric and medical outcomes for youth with HIV (YWH). Previous studies have shown that the combination of a medication algorithm and CBT tailored for YWH (COMB) is efficacious for decreasing depressive symptoms and improving quality of life, but sustainability of effects remains difficult. Most recently, a cluster-randomized RCT found at Week 24 statistically significant improvement in the site-level mean number of depressive symptoms, the proportion of YWH with a treatment response, and the proportion in remission at COMB sites compared to treatment as usual (TAU) sites (6.7 vs. 10.6, 62% vs. 18%, 48% vs.17%, ps[Formula: see text]0.01, respectively). However, by Week 48, differences were no longer significant between arms for these outcomes. Additionally, viral suppression did not improve in COMB compared to TAU. These findings indicate a “voltage drop” of COMB’s impact. To improve sustainability, we plan to enhance the combination treatment with five additional implementation strategies (COMBEX) suggested in our post-trial interviews from our efficacy study. This protocol paper describes a Hybrid Type 2 Cluster Randomized Trial in which COMBEX will be compared to COMB, with co-primary effectiveness and implementation aims guided by the Consolidated Framework for Sustainability Constructs in Healthcare.

METHODS: Eligibility will include youth with HIV (15-24 years, n = 130) with a diagnosis of ongoing nonpsychotic depression at HIV clinic sites in the US. Using restricted randomization, sites (n = 8) will be assigned to either COMBEX (with its additional implementation strategies) or to COMB. Implementation outcomes of adoption, fidelity, and sustainability will be evaluated, as well as the impact of COMBEX compared to COMB in improving real-world effectiveness of reducing indices of depression (e.g., symptoms, treatment response, remission) and decreasing viral load over 72 weeks. Additionally, an explanatory, sequential, mixed-method approach will be used to evaluate the context of implementation for both COMB and COMBEX, guided by the sustainability framework with data from staff/clinicians (n = 64). Arm comparisons will use t-tests on site-level means.

DISCUSSION: This study will inform the broader implementation of this efficacious approach to treatment of depression for youth with HIV by revealing strategies relevant to its sustainment.

TRIAL REGISTRATION: NCT07211087 (registered October 7, 2025).

PMID:42469890 | DOI:10.1186/s13012-026-01528-w

BMC Psychol. 2026 Jul 17. doi: 10.1186/s40359-026-05152-7. Online ahead of print.

ABSTRACT

BACKGROUND: Sleep problems in children are an important risk factor for cognitive, emotional, and behavioral development. Previous studies have shown that interparental conflict is closely associated with poorer sleep quality in children. However, the internal psychological variables involved in this association, particularly how they may be understood within the Chinese family context, remain insufficiently examined. Based on a sample of Chinese children, this study examined the association between interparental conflict and poorer sleep quality in children, and it tested the mediating pathways of emotional insecurity and subjective well-being(SWB).

METHODS: This study employed a quantitatively driven explanatory sequential mixed-methods design combining questionnaire survey data with child interviews. The quantitative component included 900 upper-grade primary school children (M = 10.58, SD = 0.81). Correlation analyses and a serial mediation model were used to examine the associations among interparental conflict, emotional insecurity, SWB, and children’s sleep quality. In the qualitative component, semi-structured interviews were conducted with 23 children, and thematic analysis was used to supplement and contextualize the quantitative findings.

RESULTS: Interparental conflict was significantly associated with poorer sleep quality in children (r = 0.39, p < 0.001), and this association remained significant after emotional insecurity and SWB were included as mediators in the model (β = 0.11, p = 0.006). The statistical indirect effects through emotional insecurity, through SWB, and through emotional insecurity and SWB in sequence, were all significant, with effect values of 0.014, 0.019, and 0.004 respectively. The qualitative findings showed that the interviewed children incorporated interparental conflict into their understanding of family relationships, their own situations, and daily life circumstances. Within the Chinese family context, these responses were more clearly reflected in a contextualized organization of meaning around family harmony, parent-child connection, and relational responsibility.

CONCLUSIONS: Emotional insecurity and SWB are important psychological variables for understanding the association between interparental conflict and poorer sleep quality in children. At the same time, these processes may acquire specific meanings within the Chinese family context.

PMID:42469886 | DOI:10.1186/s40359-026-05152-7

J Cardiothorac Surg. 2026 Jul 17. doi: 10.1186/s13019-026-04513-y. Online ahead of print.

ABSTRACT

BACKGROUND: Postoperative bleeding is a common and potentially life-threatening complication following cardiac surgery, often exacerbated by multifactorial coagulopathy from cardiopulmonary bypass, hypothermia, and platelet dysfunction. While fresh frozen plasma (FFP) has traditionally been used for coagulation correction, it has significant limitations, including large volume requirements, slow onset, and increased risk of transfusion-related complications. Prothrombin complex concentrate (PCC) has emerged as a potential alternative, offering rapid coagulation correction with reduced volume load and no ABO compatibility requirements. This systematic review and meta-analysis compared the efficacy and safety of PCC versus FFP in managing coagulopathic bleeding in adult cardiac surgery patients.

METHODS: We conducted a systematic review and meta-analysis following PRISMA guidelines. Electronic databases (MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials) were searched using MeSH terms and keywords related to “Cardiothoracic Surgery”, “Prothrombin Complex Concentrate”, and “Fresh Frozen Plasma”, from inception to Jan 2026. Cohort studies and randomized controlled trials comparing PCC and FFP in patients aged > 18 years undergoing cardiac surgery complicated by bleeding or coagulopathy were included. Primary outcomes were RBC transfusion requirement, chest tube drainage, and thromboembolic events. Secondary outcomes included surgical re-exploration for bleeding, stroke, duration of mechanical ventilation, hospital and ICU stays, and acute kidney injury. Risk of bias was assessed using the Cochrane Risk of Bias Tool 2.0 for RCTs and the Newcastle-Ottawa Scale for observational studies. Statistical analysis was conducted using Review Manager (RevMan) version 5.4, applying risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, both with 95% confidence intervals. The meta-analysis protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under protocol number CRD420251088737.

RESULTS: This meta-analysis included ten studies with 2,643 patients. PCC use moderately reduced RBC transfusion in the first 24 h (RR = 0.84; 95% CI: 0.76-0.93; p = 0.05; I² = 47%), 12-24-h chest tube drainage (MD = – 188.89 mL; 95% CI: – 248.48 to – 125.30; p < 0.00001; I² = 50%), and hospital stay (MD = – 1.19 days; 95% CI: – 2.21 to – 0.18; p = 0.004; I² = 67%). No significant differences were observed for surgical re-exploration (RR = 0.81; 95% CI: 0.66-1.00; p = 0.05; I² = 0%), mechanical ventilation (MD = – 0.08; 95% CI: – 0.34 to 0.19; p > 0.05; I² = 73%), ICU stay (MD = – 0.07 days; 95% CI: – 0.59 to 0.45; p = 0.78; I² = 59%), all-cause mortality (RR = 1.10; 95% CI: 0.82-1.50; p = 0.51; I² = 0%), thromboembolic events (RR = 1.22; 95% CI: 0.80-1.85; p = 0.35; I² = 0%), stroke (RR = 1.10; 95% CI: 0.75-1.63; p = 0.63; I² = 0%), acute kidney injury (RR = 1.08; 95% CI: 0.74-1.56; p = 0.70; I² = 77%), serious adverse events (RR = 0.78; 95% CI: 0.56-1.09; p = 0.15; I² = 35%), and any adverse event (RR = 0.95; 95% CI: 0.81-1.11; p = 0.54; I² = 53%). Moderate to high heterogeneity was noted in several outcomes, for which subgroup analyses were performed.

CONCLUSIONS: This meta-analysis demonstrates that PCC is superior to FFP in reducing RBC transfusion requirements, 12-24-h chest tube drainage, and hospital length of stay in adult cardiac surgery patients, while maintaining a comparable safety profile. Further large-scale, high-quality RCTs are warranted to strengthen the evidence base and inform future guidelines.

PMID:42469870 | DOI:10.1186/s13019-026-04513-y

BMC Nurs. 2026 Jul 17;25(1):634. doi: 10.1186/s12912-026-05015-x.

ABSTRACT

BACKGROUND: Hantavirus infection is uncommon in many settings but can cause severe pulmonary or renal disease. Nursing students require disease-specific preparedness for exposure-history taking, safe prevention counselling and infection prevention during community and clinical learning. This study examined undergraduate nursing students’ knowledge, risk perception and preventive practice toward hantavirus and identified associated factors.

METHODS: A descriptive analytical cross-sectional survey was conducted among 236 undergraduate nursing students in one nursing program in Ras Al Khaimah, the United Arab Emirates during the 2025-2026 academic year. Data was collected using the researcher-developed Hantavirus Knowledge, Attitudes and Preventive Practices Questionnaire for Nursing Students (HKAPP-NS). Descriptive statistics, Cronbach’s alpha, Pearson correlations and multivariable linear regression with HC3 robust standard errors were used.

RESULTS: Knowledge was low among the 236 complete-case respondents (mean 8.13/20, SD 5.84), with 59.0% classified as having poor knowledge. Attitude was moderate (mean 33.34/50, SD 7.78), and overall practice was higher (mean 42.98/64, SD 15.83). Internal consistency was strong across domains (alpha 0.886-0.967). Attitude correlated with overall practice (r = 0.569, p < 0.001), whereas knowledge did not (r = 0.101, p = 0.120). Previous hantavirus teaching, infection prevention and control training and environmental exposure predicted higher knowledge. Attitude was the strongest independent predictor of overall practice.

CONCLUSIONS: Students reported comparatively frequent precautionary practice but had important disease-specific knowledge gaps, particularly regarding safe rodent-contamination cleanup, routine vaccine availability, specific antiviral treatment and person-to-person transmission. The finding that attitude, rather than knowledge, independently predicted practice suggests that scenario-based One Health education should combine factual teaching with risk appraisal, self-efficacy building, exposure-history taking and prevention counselling to strengthen future nurses’ preparedness for rodent-borne zoonotic infections.

PMID:42469853 | DOI:10.1186/s12912-026-05015-x

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