Nevin Manimala

BMC Psychol. 2026 Jun 19. doi: 10.1186/s40359-026-05044-w. Online ahead of print.

ABSTRACT

BACKGROUND: Adverse childhood experiences (ACEs) are associated with increased risk of depressive symptoms across the life course. Medical students are exposed to sustained academic and psychosocial stress, which may interact with earlier adversity to influence mental health outcomes. However, evidence from non-Western contexts remains limited. This study examined the prevalence of ACEs and their association with depressive symptoms among Thai medical students.

METHODS: A cross-sectional study was conducted between April and July 2025 among medical students at one faculty of medicine and two affiliated medical education centers in Southern Thailand. All participants completed an anonymous online survey that included the Thai version of the Adverse Childhood Experiences questionnaire and the validated Thai version of the Patient Health Questionnaire-9 (PHQ-9). ACE exposure was categorized as low (0-1), moderate (2-3), and high (≥ 4). Depressive symptoms were defined as PHQ-9 scores ≥ 9. Multivariable logistic regression analyses were performed to examine associations between ACE exposure and depressive symptoms, adjusting for demographic variables, physical illness, and recent life stress.

RESULTS: Among 540 participants (median age 21 years; 60.4% female), 54.6% reported at least one ACE. Moderate and high ACE exposure were observed in 20.2% and 6.7% of students, respectively. The most commonly reported ACE domains were physical neglect (31.9%), parental divorce or separation (28.8%), and household mental illness (26.8%). Depressive symptoms were present in 17.6% of participants. In multivariable analyses, moderate ACE exposure was independently associated with depressive symptoms (adjusted odds ratio [aOR] = 2.26; 95% CI: 1.29-3.93; p = 0.004). High ACE exposure showed a similar magnitude of association but did not reach statistical significance. Current life stress (aOR = 5.83; 95% CI: 2.77-14.31; p < 0.001) and physical illness (aOR = 2.30; 95% CI: 1.19-4.36; p = 0.012) were also independently associated with depressive symptoms.

CONCLUSION: ACEs were common among Thai medical students and were associated with higher odds of depressive symptoms after adjustment for current stressors. These findings highlight the role of early-life adversity as a potential vulnerability factor for psychological distress in medical training. Longitudinal research is warranted to clarify temporal pathways and inform culturally appropriate mental health support strategies in medical education settings.

PMID:42321925 | DOI:10.1186/s40359-026-05044-w

Pilot Feasibility Stud. 2026 Jun 20. doi: 10.1186/s40814-026-01862-2. Online ahead of print.

ABSTRACT

BACKGROUND: Cognitive difficulties are common in people with multiple sclerosis (MS) and predict poorer quality of life, yet effective treatment is lacking. Cognitive remediation therapy (CRT) improves functioning in individuals with severe mental health conditions and could benefit people with MS if adequately adapted. Recognising patient and public involvement (PPI) benefits in developing acceptable interventions, this study engaged people with MS to develop a protocol to assess the feasibility of delivering a computerised, therapist-assisted CRT programme (CIRCuiTS™) to people with MS. This paper describes this process and presents the trial protocol, highlighting how PPI informed the study design and treatment implementation.

METHODS: Protocol co-development involved three phases of consultation with people with MS. First, the PPI lead, who has MS, contributed along with mental health professionals to the design draft. Second, co-development using an observational qualitative design was conducted with people with MS in a structured 2-day workshop. Workshop discussions were recorded, transcribed, and analysed thematically to arrive at 24 specific, actionable recommendations. These recommendations, alongside statistical input, guided the trial design. Finally, a separate PPI group provided feedback on the trial documents. The proposed trial will recruit 24 people with MS experiencing cognitive difficulties from a UK NHS service, randomly assigning them to receive a 12-week CIRCuiTS™ MS programme immediately or after a 13-week wait. This relatively short waiting period was recommended as likely to maintain engagement. Standard CIRCuiTS™ delivery will be adapted to MS needs by offering remote sessions, dexterity tailoring and MS-specific therapist training. Primary outcomes are feasibility and acceptability. Guided by PPI-anticipated benefits, the secondary outcomes will be goal attainment, cognition, fatigue, mood, and daily functioning. Two people with MS continue to guide the study in the oversight group and a PPI Advisory group will provide ongoing advice on trial management.

DISCUSSION: PPI, as recommended in the new CONSORT 2025 statement, strengthened the feasibility and acceptability of the trial by addressing challenges and shaping the protocol. This collaboration enhances the evaluation of CRT for people with MS and provides a model for transparent PPI reporting in trial development.

TRIAL REGISTRATION: ClinicalTrials.gov ID NCT06877273, 14th March 2025.

PMID:42321924 | DOI:10.1186/s40814-026-01862-2

J Cannabis Res. 2026 Jun 19. doi: 10.1186/s42238-026-00463-3. Online ahead of print.

ABSTRACT

BACKGROUND: Hypertension is a leading risk factor for cardiovascular disease, particularly in ageing populations. While pharmacological interventions are common, issues with long-term adherence and side effects have prompted interest in alternative treatments. Cannabidiol (CBD), a non-psychoactive component of Cannabis sativa, has been proposed as a potential agent for blood pressure regulation due to its anxiolytic, anti-inflammatory, and vasodilatory properties. This systematic review aimed to evaluate the effects of oral CBD supplementation on blood pressure in adults with normotension and hypertension.

METHODS: A systematic search of PubMed, Web of Science, Scopus, and Medline was conducted in September 2024. Eligible studies were randomised controlled trials (RCTs) involving oral CBD administration in normotensive or hypertensive adults, with blood pressure as an outcome. Studies involving animals, inhaled CBD, or non-English texts were excluded. Risk of bias was assessed using the Cochrane Risk of Bias tool. Clinical heterogeneity was assessed by comparing study populations, CBD dosing regimens, outcome measures, and assessment conditions. Substantial variability in dosing and blood pressure outcome reporting precluded quantitative pooling; therefore, results were synthesised narratively due to clinical heterogeneity.

RESULTS: Four RCTs involving 120 participants met the inclusion criteria. Studies varied in CBD dose (225-600 mg/day), duration (two hours to 5 weeks), and participant health status. An association was observed between CBD dosage (mg/day) and reductions in blood pressure indicators, with greater reductions occurring at higher doses. All four studies reported statistically significant reductions in systolic blood pressure compared to placebo, particularly under stress or during sleep. Two studies reported lower diastolic pressure. The strongest effects were observed with acute administration of the highest-dose studies of 600 mg/day. Side effect severity was generally mild to moderate, including nausea, diarrhoea, and fatigue. No serious cardiovascular events were reported.

CONCLUSION: Oral CBD may reduce blood pressure amongst healthy and hypertensive individuals, particularly under stressful conditions and during sleep. Limitations included small sample sizes, short trial durations, variability in CBD matrices and dosages, lack of pharmacokinetic data, and uncertainty surrounding hepatic safety. Larger, longer-term trials with homogeneous supplementation strategies and bioavailability measures are needed to determine CBD’s therapeutic role in blood pressure management.

PMID:42321899 | DOI:10.1186/s42238-026-00463-3

Confl Health. 2026 Jun 19. doi: 10.1186/s13031-026-00815-z. Online ahead of print.

ABSTRACT

BACKGROUND: Access to essential medicines is a fundamental human right and a critical pillar of effective healthcare. In Africa, armed conflicts severely weaken health systems, disrupting the availability of essential medicine, leading to gaps in patients’ treatment and, in turn, posing a serious risk to overall public health. Therefore, this study aimed to identify the impact of armed conflicts on the availability of essential medicines as a cornerstone of healthcare across African regions, and quantify the extent of this disruption over time and by country.

METHODS: In this systematic review and meta-analysis, data were retrieved from published articles accessible in PubMed, Semantic Scholar, and grey literature covering the period from 1985 to 2025 and 2001 to 2024 for system impact and medicines availability studies, respectively. The literature search was conducted from January to May 2025. Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, studies were independently screened by two reviewers and included if they contained information on medicine availability or its relation to health systems in conflict zones and were published in English. The quality of studies was evaluated using the Joanna Briggs Institute criteria. Pooled estimates of medicine availability and their 95% CIs were obtained using a random-effects analysis. Heterogeneity was assessed using the I² statistic. The risk of bias and small study effects were assessed with funnel plots and Egger’s test. Additionally, the leave-one-out sensitivity test and influence diagnostics test were considered to evaluate study-level impact.

RESULTS: The review included data from 1,581 health facilities and 989 essential medicines across eight conflict-affected African countries. The pooled availability of essential medicines calculated from the data obtained from 41 studies conducted in African countries shouldering frequent armed conflict was estimated at 55% (95% CI, 47-63), with substantial heterogeneity across studies (I² = 93%, p < 0.001). Country-level analysis showed the highest availability in the Central African Republic (79%; 95% CI, 49-95) and the lowest in Nigeria (40%; 95% CI, 1-78). A temporal decline in medicine availability was observed, from 76% (2001-2010) to 46% post-2020. No significant publication bias was detected (funnel plot asymmetry p = 0.9560; Egger’s test p = 0.494). Additionally, the influence diagnostic test and the leave-one-out sensitivity analysis indicated that observed heterogeneity likely reflects methodological differences and the sample size across the studies rather than bias or outliers. The systematic review revealed that armed conflicts have profoundly compromised health system functionality through the destruction of healthcare infrastructure, closure of medical facilities, displacement of the health workforce, pervasive insecurity and psychological distress among healthcare providers, and disruptions in supply chains and transportation networks, all of which have adversely affected the accessibility of essential medicines.

CONCLUSION: On average, only 55% of essential medicines were available in conflict-affected regions of Africa, which was below the WHO benchmark of 80%. This finding underscores the severe threat that armed conflict poses to medicine availability and, consequently, to increased indirect morbidity and mortality. Additionally, the conflict undermines medicine availability through multiple, often interconnected mechanisms, indicating the need for a coordinated, multisectoral approach to ensure continuous access to essential medicines. Therefore, strengthening healthcare infrastructure in conflict settings is critical. Furthermore, the international community should enforce accountability mechanisms for violations affecting healthcare services, while donors and regional humanitarian assistance and emergency response mechanisms should increase investment and medicine supply in resilient medicine supply systems capable of maintaining availability during periods of armed conflict.

STUDY PROTOCOL REGISTRATION: The study protocol was registered in PROSPERO (CRD420251154811), the International Prospective Register of Systematic Reviews, maintained by the National Institute for Health and Care Research (NIHR).

PMID:42321895 | DOI:10.1186/s13031-026-00815-z

Chiropr Man Therap. 2026 Jun 19. doi: 10.1186/s12998-026-00659-7. Online ahead of print.

ABSTRACT

BACKGROUND: The back squat is a commonly prescribed exercise for developing lower body strength. The ability to squat can be affected by reduced ankle dorsiflexion range of motion (DF-ROM), leading to limited squat depth and dysfunctional compensatory movement patterns.

OBJECTIVE: To investigate the effect of high-velocity low-amplitude lower limb manipulations on 1 repetition maximum (1RM) back squat strength, sagittal plane ankle kinematics during a squat, and active DF-ROM in individuals with asymptomatic deficits in DF-ROM.

METHODS: Twenty-six enrolled; Twenty-four analysed resistance-trained participants with asymptomatic deficits in DF-ROM participated in this double-blind randomised sham-controlled cross-over trial. Interventions involved high-velocity low-amplitude joint manipulations targeting ankle DF-ROM, and a sham which mimicked the manipulations using a mechanical drop mechanism. The primary outcome was a change in back squat 1RM between baseline to post-intervention, with secondary outcomes being maximal ankle DF-ROM during the 1RM squat using 3D motion capture, and change in DF-ROM during the weightbearing lunge test.

RESULTS: There was no statistically significant difference between interventions for back squat 1RM (p = 0.27). From baseline, the 1RM increased by 4.75 kg (3.6%) following manipulation and 2.75 kg (2.1%) following the sham. There were no statistically significant differences between interventions on maximal DF-ROM during the back squat (p = 0.24) and no statistically significant differences in ankle DF-ROM immediately following either intervention (p = 0.39).

CONCLUSION: Based on these results a single session of high-velocity low-amplitude manipulations targeting ankle DF-ROM does not significantly improve 1RM back squat strength compared to sham, and does not influence short-term ankle DF-ROM. Trial registration The study was pre-registered with ANZCTR (ACTRN12622000811707).

PMID:42321886 | DOI:10.1186/s12998-026-00659-7

Ital J Pediatr. 2026 Jun 19. doi: 10.1186/s13052-026-02298-3. Online ahead of print.

ABSTRACT

BACKGROUND: The 2024 international pediatric sepsis consensus definition has undergone a paradigm shift from a systemic inflammatory response syndrome (SIRS)-based framework to the organ dysfunction-centered Phoenix Sepsis Criteria (PSC). We aimed to evaluate the diagnostic concordance, predictive performance for 28-day pediatric intensive care unit (PICU) mortality, and phenotypic overlap between these two pediatric sepsis definitions.

METHODS: This single-center retrospective cohort study included 1034 children aged > 1 month to < 18 years with confirmed or suspected infection who were directly admitted to the PICU of Children’s Hospital of Chongqing Medical University between January 1, 2020, and November 21, 2023. All patients were independently evaluated for sepsis using both the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) SIRS criteria and the 2024 PSC. Diagnostic agreement was assessed using the Kappa coefficient. Binary logistic regression was employed to establish association models between factors and phenotypes, as well as between factors and PICU 28-day mortality. Predictive performance was compared using the C-statistic.

RESULTS: Among 1034 patients, 613 (59.3%) met the Sepsis-SIRS criteria with a 28-day PICU mortality of 15.2% (93/613), 744 (72.0%) met the Sepsis-Phoenix criteria with a mortality of 16.3% (121/744), 489 (47.3%) met both criteria with a mortality of 18.6% (91/489), and 166 (16.1%) met neither criterion with a mortality of 2.4% (4/166). Agreement between the two criteria was poor (kappa = 0.202, 95% CI: 0.143-0.261). After adjusting for clinically relevant confounders, the PSC remained a strong independent predictor of 28-day mortality (adjusted OR = 5.123, 95% CI: 2.128-12.333, p < 0.001), whereas the SIRS criteria showed no independent predictive value (adjusted OR = 0.937, 95% CI: 0.523-1.678, p = 0.827). The PSC demonstrated significantly superior discriminatory ability compared with the SIRS criteria (C-statistic = 0.809 vs. 0.589, p < 0.001). Notably, 20.2% of SIRS-positive patients were not classified as sepsis by the Phoenix Criteria, and this subgroup had an extremely low mortality of 1.6%, reflecting higher specificity of the PSC.

CONCLUSIONS: The SIRS and PSC identify partially overlapping populations with distinct risk stratification, showing poor diagnostic concordance. The PSC has superior independent predictive performance for PICU 28-day mortality and may be considered for prognostic assessment of infected children in the PICU setting. Importantly, historical study results based on the SIRS criteria should be extrapolated cautiously to PSC-defined populations.

PMID:42321878 | DOI:10.1186/s13052-026-02298-3

BMC Psychol. 2026 Jun 19. doi: 10.1186/s40359-026-04960-1. Online ahead of print.

ABSTRACT

BACKGROUND: Combat athletes face unique psychological demands, and stress may influence both their cognitive experiences and psychological well-being. This study aimed to examine the mediating role of mental fatigue awareness in the relationship between perceived stress and psychological well-being among combat athletes, thereby contributing to a clearer understanding of a potential cognitive mechanism linking stress to well-being in this population.

METHODS: A total of 303 combat athletes voluntarily participated. Participants completed the Perceived Stress Scale, Mental Fatigue Awareness Scale, and Psychological Well-being Scale. Statistical analyses assessed the direct effects of perceived stress on psychological well-being, the effect of stress on mental fatigue awareness, and the potential mediating role of mental fatigue awareness.

RESULTS: Perceived stress significantly increased mental fatigue awareness (b = 0.732, SE = 0.064, β = 0.549, p = 0.001) and directly decreased psychological well-being (b = – 0.488, SE = 0.166, β = – 0.191, p = 0.004). Mental fatigue awareness negatively affected psychological well-being (b = – 0.374, SE = 0.124, β = – 0.195, p = 0.003) and partially mediated the relationship between stress and well-being (indirect effect: b = – 0.274, SE = 0.115, β = – 0.107, p = 0.003; 95% CI = – 0.504 to – 0.049).

CONCLUSION: Perceived stress was associated with psychological well-being both directly and indirectly through increased mental fatigue awareness. These findings suggest that mental fatigue awareness may represent a relevant cognitive pathway linking stress perceptions to well-being. Accordingly, stress management and strategies aimed at regulating mental fatigue may be considered as potentially beneficial components in efforts to support psychological well-being among combat athletes.

PMID:42321877 | DOI:10.1186/s40359-026-04960-1

BMC Vet Res. 2026 Jun 20. doi: 10.1186/s12917-026-05577-7. Online ahead of print.

ABSTRACT

BACKGROUND: As the threat of antimicrobial resistance (AMR) escalates globally, the influence of indiscriminate antimicrobial use (AMU) in livestock cannot be overlooked. Antimicrobial use practices are continually explored in larger food-producing animals; however, small ruminants (sheep and goats) receive comparatively less research attention. Our study addresses this gap by investigating small ruminant production practices in Nigeria and exploring how they affect the use of antimicrobials and alternatives.

METHODS: We adopted a mixed-methods study design. A semi-structured questionnaire was administered to 785 farmers. Following this, a focus group discussion (FGD) was conducted with 23 small ruminant industry stakeholders, which included farmers, para-veterinarians, and butchers. Participants were split into three round tables, with 7-8 participants per table.

RESULTS: Of questionnaire respondents, 68% of farmers never vaccinated their flock against peste de petits ruminants (PPR) nor contagious caprine pleuropneumonia virus. Several health problems were regularly experienced by animals, including PPR, mastitis, and dermatophilosis. Diseases were mostly self-managed with antibiotics and herbs (> 70%) rather than through reliance on veterinary care (< 15%). More farmers (48%) used antibiotics than herbal remedies (14%) over the previous three months. Farmers’ use of herbs was affected by their having low awareness of available options and how to use them appropriately. Perceived effectiveness also influenced farmers’ choice between antibiotics and herbs, while economic considerations also led them to sell off sick animals before or during treatment. Among farmers who used animal health services, more farmers (59%) consulted unlicensed para-veterinarians and drugstore vendors rather than licensed government and private veterinarians (36%), a disparity attributed to the unavailability of qualified veterinary doctors. Most farmers had poor knowledge (62%), attitudes (47%), and practices (43%) towards AMU and AMR.

CONCLUSIONS: We recommend conducting further studies to identify and investigate the efficacy of currently used herbs in treating common diseases. There is a crucial need to improve farmers’ access to vaccines, veterinary care, and laboratory diagnostics. Barriers that hinder better compliance with regulations that govern the use of non-prescribed antimicrobials should be explored. Awareness programmes could be conducted to improve farmers’ awareness of AMR and appropriate disease preventive practices.

PMID:42321859 | DOI:10.1186/s12917-026-05577-7

Epigenetics Chromatin. 2026 Jun 19. doi: 10.1186/s13072-026-00685-y. Online ahead of print.

ABSTRACT

BACKGROUND: Asthma is a clinically heterogeneous airway disorder characterized by complex interactions between environmental exposures, immune activation, and molecular regulatory programs, whose underlying mechanisms are not fully elucidated by known genetic loci. DNA methylation serves as a mechanistic interface bridging genetic predisposition and environmental influences; however, most epigenetic studies remain confined to isolated CpG sites, lacking robust biological interpretability.

METHODS: We developed a cross-tissue, multi-cohort, and mechanistically interpretable epigenetic framework to delineate pathway-level methylation mechanisms underlying asthma. Leveraging data from 908 participants across one combined training cohort and three independent validation cohorts, we constructed a linear support vector classifier based on pathway-derived methylation scores. Additionally, SHapley Additive exPlanations (SHAP) were applied to quantify the contributions of individual pathways. To assess the statistical significance of pathway contributions, one-sample t-tests were performed for each pathway’s SHAP values against zero, followed by Benjamini-Hochberg false discovery rate (FDR) correction to obtain adjusted p values.

RESULTS: The model exhibited reproducible and cross-tissue performance, achieving area under the curve (AUC) values of 0.792 (95% CI: 0.782-0.799; GSE65163) and 0.980 (95% CI: 0.974-0.990; GSE201872) in two airway epithelial cohorts, and 0.736 (95% CI: 0.690-0.771; GSE104471) in peripheral blood samples. Pathway interpretability analyses identified dominant roles of amino acid metabolism, epithelial and mesodermal developmental programs, metabolic-immune transport pathways, and neuroimmune signalling in shaping asthma-associated methylation patterns. Mediation analyses further revealed that these pathways influence asthma both directly and indirectly via eosinophil activity, epithelial proliferative dynamics, and nitric oxide-linked airway inflammation. Notably, pathways annotated by GO:0061205 and GO:0098727 exerted significant direct effects independent of immune intermediates.

CONCLUSIONS: This study describes a pathway-level methylation model designed for biological interpretability that shows associations with both clinical severity and latent molecular heterogeneity. It provides statistical evidence contributing to the understanding of epigenetic, immune, and metabolic signatures in asthma, offering a potential framework warranting further validation for precision respiratory medicine.

PMID:42321852 | DOI:10.1186/s13072-026-00685-y

Cancer Imaging. 2026 Jun 20. doi: 10.1186/s40644-026-01069-x. Online ahead of print.

ABSTRACT

Hypoxia is associated with poor outcomes in soft tissue sarcoma (STS) and is linked to increased expression of hypoxia-inducible factor 1-alpha (HIF-1α), carbonic anhydrase IX (CAIX), and lysyl hydroxylase 2 (PLOD2). These factors are potential therapeutic targets. This exploratory study aimed to investigate the correlation between ¹⁸F-fluoromisonidazole (¹⁸F-FMISO) positron emission tomography (PET) imaging, a marker of hypoxia, and the expression of these biomarkers in STS. This imaging phase II clinical trial (NCT #03730077) recruited 5 patients with suspected soft tissue sarcoma (STS) and imaged these patients with ¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG) and ¹⁸F-FMISO within 2 weeks of each other. STS tissue was analyzed for HIF-1α, CAIX, and PLOD2 expression using immunohistochemistry and western blotting. Collagen formation was assessed by Masson’s trichrome. In this small sample, a correlation was found between STS size and PLOD2 expression (r = 0.996, P = 0.004). STS grade correlated positively with ¹⁸F-FMISO T/M (tumor/muscle) SUVmax (r = 0.894, P = 0.041). ¹⁸F-FDG correlated positively with ¹⁸F-FMISO SUVmax (r = 0.994, P = 0.006). Positive but non-significant associations were noted between ¹⁸F-FMISO T/M SUVmax and CAIX (r = 0.95, P > 0.05) and PLOD2 (r = 0.93, P > 0.05). These preliminary observations in a small sample are hypothesis-generating at best and must be interpreted with substantial caution due to the extremely limited number of patients, which precludes robust statistical inference and generalizability. No definitive conclusions can be drawn regarding the relationship between 18F-FMISO uptake and hypoxia biomarker expression. Larger, adequately powered prospective studies are essential to validate these findings, clarify potential correlations, and determine the clinical utility of 18F-FMISO PET/CT as a noninvasive hypoxia biomarker in STS.

PMID:42321847 | DOI:10.1186/s40644-026-01069-x