Category: Nevin Manimala

Environ Int. 2025 Aug 28;203:109762. doi: 10.1016/j.envint.2025.109762. Online ahead of print.

ABSTRACT

BACKGROUND: Testicular germ cell cancer (TGCC) originates during fetal life. Fetal exposure to environmental chemicals may contribute to its development, but epidemiological data are lacking. We investigated per- and polyfluoroalkyl substances (PFAS), which can act as endocrine disruptors during fetal development, and TGCC risk in adulthood.

METHODS: We conducted a nested case-control study of 549 mother-male offspring pairs (103 TGCC cases, 446 matched controls). The source population included over 100,000 pregnant women with biobanked serum samples collected during 1985-1994, a period before PFAS restrictions. Male offspring were followed for up to 38 years, and TGCC cases were identified from the Danish Cancer Registry based on histological confirmation. Eight PFAS were quantified in maternal serum using LC-MS/MS. Associations between individual PFAS and their mixtures with TGCC risk were assessed through Cox regression and quantile g-computation models.

RESULTS: Associations between individual PFAS and TGCC risk were modest and not statistically significant. Hazard ratios (HRs) for perfluoroalkyl sulfonic acids (PFOS, PFHxS, PFHpS) suggested higher TGCC risks per quartile increase in concentrations, but lower risks for perfluoroalkyl carboxylic acids (PFOA, PFNA, PFDA, PFHpA, PFUnDA). Mixture analyses supported this pattern, with higher TGCC risk for the joint effect of sulfonic acids (HR 1.13, 95 % CI: 0.89; 1.44). Stratified analyses by histological subtype showed higher risk for seminomas than for nonseminomas across all PFAS.

CONCLUSIONS: We found limited evidence of an association between fetal PFAS exposure and TGCC risk. Indications of a potential adverse effect of perfluoroalkyl sulfonic acids, particularly for seminomas, merit further research.

PMID:40902259 | DOI:10.1016/j.envint.2025.109762

J Behav Ther Exp Psychiatry. 2025 Aug 31;90:102069. doi: 10.1016/j.jbtep.2025.102069. Online ahead of print.

ABSTRACT

This study explored the relationships between dissociative experiences, childhood trauma, maladaptive schemas, schema modes, and schema coping in a nonclinical sample. Three theoretical models were tested: (1) dissociative experiences resulting from schema mode activation, (2) dissociative experiences as an innate trait shaping schema coping, and (3) dissociative experiences arising from childhood trauma that influence coping strategies. Data from 401 Dutch psychology students were analyzed using path analyses to compare model fit. While all models showed good fit, Model 2 emerged as the best based on AIC and BIC values. This model linked dissociative experiences to avoidance and surrender coping styles and specific schema modes, such as the punitive parent and detached self-soother. Findings suggest dissociative experiences shape responses to schema-related stress through disengagement or immersion. Future research in clinical populations is recommended to further explore these dynamics and their therapeutic relevance.

PMID:40902253 | DOI:10.1016/j.jbtep.2025.102069

Ecotoxicol Environ Saf. 2025 Sep 2;303:118981. doi: 10.1016/j.ecoenv.2025.118981. Online ahead of print.

ABSTRACT

BACKGROUND: Carotid atherosclerosis (CAS) is a major contributor to cerebrovascular incidence and mortality, yet its etiology in non-dyslipidemic individuals remains poorly understood. Emerging evidence suggests that environmental metal exposure may play a critical role in CAS development.

METHODS: We conducted a retrospective matched case-control study involving 1290 non-dyslipidemic middle-aged and elderly individuals to examine the association between urinary metal exposure and CAS. Twenty-eight urinary metals were measured using inductively coupled plasma mass spectrometry (ICP-MS), and statistical analyses-including conditional logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR)-were applied to assess single and mixed-metal effects. Mediation analysis was performed to evaluate the potential role of metabolic and inflammatory clinical indicator.

RESULTS: Conditional logistic regression found that six metals (OR_Q4vsQ1=1.63, 95 %CI: 1.14-2.34 for lithium (Li); OR_Q4vsQ1= 1.65, 95 %CI: 1.16-2.35 for titanium (Ti); OR_Q4vsQ1= 1.53, 95 %CI: 1.07-2.22 for cobalt (Co); OR_Q4vsQ1= 1.77, 95 %CI: 1.24-2.51 for nickel (Ni); OR_Q4vsQ1= 1.93, 95 %CI: 1.33-2.79 for copper (Cu), and OR_Q4vsQ1= 2.14, 95 %CI: 1.45-3.18 for cadmium (Cd)) were significantly associated with increased CAS risk, while selenium (Se) (OR _Q2vsQ1 = 0.65, 95 %CI: 0.46-0.93, OR_Q2vsQ1 = 0.59, 95 %CI: 0.41-0.84) was negatively associated with the risk of CAS. Mixed-metal exposure analyses, including WQS (OR=1.35, 95 %CI 1.12-1.63) and BKMR, consistently demonstrated a positive correlation with CAS, primarily driven by Ti. Mediation analysis further revealed that 11.54 % of association between Cu and CAS explained by remnant cholesterol (RC).

CONCLUSION: Our findings revealed a significant correlation between environmental metal exposure and CAS, independent of traditional lipid abnormalities. Future prospective studies are warranted to confirm these associations and elucidate the underlying biological mechanisms, potentially guiding targeted prevention strategies.

PMID:40902247 | DOI:10.1016/j.ecoenv.2025.118981

Drug Alcohol Depend. 2025 Aug 22;276:112848. doi: 10.1016/j.drugalcdep.2025.112848. Online ahead of print.

ABSTRACT

INTRODUCTION: Through secondary data analyses, we investigated sex differences in the effects of IQOS, a heated tobacco product, on combustible cigarette smoking.

METHODS: Adults who smoke cigarettes (N = 118; 21-65 years old) completed a baseline ad-lib smoking period (days 1-5), two laboratory visits (days 6-7), and a 14-day period where they were instructed to switch from smoking cigarettes to using IQOS 3.0 (days 8-21). Models estimated the changes in cigarettes smoked per day (CPD) and the percentage of baseline CPD substituted by HeatSticks during the switch period. Bivariate statistics assessed sex differences in covariates and IQOS-associated effects (i.e., subjective reward, relative reinforcing value, craving relief, and withdrawal relief) for model inclusion.

RESULTS: Males and females significantly reduced their CPD to 29.8 % and 21.8 % of their baseline CPD by the end of the switch period, respectively. CPD slopes were significant for males (β =-0.46/day [CI95 % -0.97 to -0.04] p = 0.002) and females (β =-0.83/day [CI95 % -1.34 to -0.31] p < 0.001), although slopes did not significantly differ (p = 0.3). Males and females substituted HeatSticks at 83.2 % and 67.4 % of their baseline CPD across the switch period. The IQOS slopes were significant for males (β =1.136/day [CI95 % 0.59-2.14] p = 0.001) but not females (β =0.64/day [CI95 % -0.67-1.94] p = 0.34), although the slopes did not significantly differ (p = 0.36). There were no significant sex differences in IQOS-associated effects (all p values > 0.05).

CONCLUSIONS: Males and females do not appear to differ in IQOS-associated effects or the initial substitutability of IQOS for combustible cigarettes.

PMID:40902222 | DOI:10.1016/j.drugalcdep.2025.112848

Clin Nutr. 2025 Aug 23;53:109-118. doi: 10.1016/j.clnu.2025.08.025. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: The association between meat intake and breast cancer risk remains unclear. This study examined the relationship between specific types of meat intake and breast cancer risk in a prospective cohort study.

METHODS: This study included 71,264 women aged 40-69 years from the Health Examinees-Gem (HEXA-G) study (2004-2013). Cancer diagnosis was identified via the Korea Central Cancer Registry and death certificate-linked data were provided by the Korea National Statistical Office until 31 December 2018. Cox proportional hazards models were used to estimated multivariate hazard ratios (HRs) and 95 % confidence intervals (CIs) for breast cancer risk by meat intake.

RESULTS: During 655,566.9 person-years of follow-up, 713 breast cancer cases were identified. Women who consumed one or more servings of processed meat per week had a 57 % increased risk of breast cancer (HR = 1.57, 95 % CI: 1.09-2.27, p for trend = 0.003), compared to those who did not consume processed meat. Stronger associations were observed among women under 50 years of age (p for trend = 0.021), with no family history of breast cancer (p for trend = 0.001), no regular exercise (p for trend = 0.028), no alcohol consumption (p for trend = 0.002) and a body mass index (BMI) below 25 kg/m² (p for trend = 0.005). Beef intake was associated with a potential reduction in breast cancer risk (HR = 0.82, 95 % CI: 0.67-1.01, p trend = 0.051, for 2 or more servings per month vs. none). Also, reduction of breast cancer risk was observed in women who consumed alcohol (p for trend = 0.036). More pronounced associations were found in women without family history of breast cancer (p for trend = 0.049), and in women who did not engage in regular exercise (p for trend = 0.015).

CONCLUSIONS: Our results suggest that processed meat intake is linked to a higher risk of breast cancer, whereas beef consumption may reduce the risk of breast cancer.

PMID:40902216 | DOI:10.1016/j.clnu.2025.08.025

Semin Arthritis Rheum. 2025 Aug 28;74:152822. doi: 10.1016/j.semarthrit.2025.152822. Online ahead of print.

ABSTRACT

OBJECTIVE: A revision of the 2017 EULAR-ACR myositis classification criteria, namely EULAR-ACR funded Myositis Revision of Classification (MyoROC) project, is currently underway involving a large international group of experts. In the first phase of this project, we identified additional items to be tested in the criteria.

METHODS: We distributed an electronic survey to International Myositis Assessment and Clinical Studies (IMACS) members to identify new items. The identified items were discussed within the Steering Committee and a multi-step Delphi consensus process consisting of an open discussion and three rounds of e-voting were conducted to reach the final item list.

RESULTS: The IMACS survey results revealed 24 new items. After an open discussion with Steering Committee members, 14 items were dropped and five new items were added, resulting in a total of 15 items. After three rounds of e-voting, the following variables were agreed to be tested in addition to the original items: finger flexion, knee extension ≥ hip flexion weakness, myonecrosis pattern on biopsy, magnetic resonance imaging and electromyography findings of myositis, additional rashes, skin biopsy, capillaroscopy, interstitial lung disease, arthritis, Raynaud’s phenomenon, myositis-specific (MSA) and -associated autoantibodies, enzyme elevation at ≥2 time points, and aldolase.

CONCLUSION: The new items that will be tested in the revised criteria were generated with input from a wide range of stakeholders and included, most importantly, MSA, pattern of weakness, skin changes, and additional diagnostic modalities. The next steps of the project are data collection followed by statistical analysis for development and validation of the revised criteria.

PMID:40902212 | DOI:10.1016/j.semarthrit.2025.152822

JMIR Med Educ. 2025 Sep 3;11:e65053. doi: 10.2196/65053.

ABSTRACT

BACKGROUND: The necessity for self-regulated, lifelong learners in the rapidly evolving field of medicine underscores the importance of effective study skills. Efforts to support students with these skills have had positive outcomes but are often limited in scope and accessibility, with a tendency to target groups facing immediate challenges.

OBJECTIVE: This study aimed to explore the student perspective on study skills support at University College London Medical School through a student-staff partnership, with the goal of guiding future improvements.

METHODS: A mixed methods approach was adopted using an anonymous questionnaire and focus groups. After analyzing questionnaire responses using descriptive statistics to refine focus group questions, focus groups were conducted to delve deeper into identified issues. Transcripts were analyzed thematically using inductive coding.

RESULTS: In total, 116 students completed the questionnaire in full and 6 students participated in 2 focus groups. The questionnaire revealed that 68% (68/100) of respondents felt that they never received study skills support at University College London Medical School. Preferred methods of support included small group sessions (56/100, 56%) and topics like examination preparation (83/100, 83%) and study skills specific to medicine (72/100, 72%). Focus group themes were the lack of current study skills support, delivery of study skills support, specific study skills for medical school, personalized approach to support needed, and accessing support. Findings informed the co-creation of study skills resources.

CONCLUSIONS: Overall, the findings highlight the need for strategically incorporating study skills support at medical school, emphasizing early and consistent promotion and tailored delivery methods.

PMID:40902194 | DOI:10.2196/65053

Medwave. 2025 Sep 3;25(8):e381. doi: 10.5867/medwave.2025.08.3081.

ABSTRACT

INTRODUCTION: The COVID-19 pandemic had a major impact on emergency services, including stroke care. Changes in the administration times of brain reperfusion therapies for stroke have been little explored in Chile. The aim of this study was to analyze the impact that the pandemic had on critical stroke treatment times, the number of patients treated, clinical severity, and the presence of major vessel occlusion.

METHODS: We performed a retrospective analysis of patients undergoing encephalic reperfusion therapy in a hospital in Valparaíso, Chile. Two groups of patients treated one year before (pre-pandemic group) and one year after (pandemic group) the start of health restrictions were compared.

RESULTS: 104 patients were included, with a mean age of 67.4 ± 13 years and a clinical severity of 13.5 ± 6.5 in the NIHSS. 91.5% received thrombolytic therapy. No significant intergroup differences were found in the metrics of treatment time, number of patients treated, clinical severity, or presence of major vessel occlusion. Although there was a non-significant trend towards delayed institutional therapeutic times, a significant correlation was found suggesting that the shorter the time from symptom onset to door, the shorter the time to access therapy (r = 0.84).

CONCLUSIONS: There were no significant differences in the therapeutic times of stroke in the period prior to the COVID-19 pandemic and the pandemic period, showing similarities to the experience reported in Chile and highlighting the adaptation of the health system during the health crisis. Studies with more complex epidemiological designs analyzing larger samples of patients will allow us to complement these results.

PMID:40902137 | DOI:10.5867/medwave.2025.08.3081

J Clin Oncol. 2025 Sep 3:JCO2402644. doi: 10.1200/JCO-24-02644. Online ahead of print.

ABSTRACT

PURPOSE: Patients with advanced, well-differentiated extrapancreatic neuroendocrine tumors (epNETs) have limited systemic treatment options. Pazopanib, an oral multikinase inhibitor with activity against vascular endothelial growth factor receptor (VEGFR)-2 and -3, PDGFR-alpha and-beta, and c-Kit, was tested for efficacy in epNET.

PATIENTS AND METHODS: We conducted a multicenter, randomized, double-blind, phase II study of pazopanib (800 mg once daily) versus placebo in low- to intermediate-grade epNET with radiologic progressive disease (PD) within 12 months of study entry. Previous somatostatin analog (SSA) was required for midgut tumors, and concurrent SSA was allowed. The primary end point was progression-free survival (PFS) by blinded independent central review. Unblinding and crossover were allowed if PD was confirmed by central review.

RESULTS: One hundred seventy-one patients (97 pazopanib and 74 placebo) were randomly assigned between September 2013 and October 2015. The majority had a midgut primary site (75%) and previous SSA treatment (93%). About half (49%) of the patients had functional tumors. The median follow-up was 61 months (95% CI, 60 to 63). Median PFS was 11.8 versus 7.6 months in pazopanib versus placebo, respectively (hazard ratio, 0.54 [95% CI, 0.37 to 0.79]; P < .001); 49 placebo patients crossed over to pazopanib. There was no significant difference in overall survival between the treatment arms. Rates of grade 3 or greater adverse events (regardless of attribution) were higher in pazopanib versus placebo (84% v 47%; P < .001), as were grade 5 death events (8% v 0%, P = .017).

CONCLUSION: Pazopanib compared with placebo significantly improves PFS in patients with progressive epNET, confirming that the VEGF signaling pathway is a valid target for therapy in epNET. However, after integrating the associated risks relative to the benefits, further development of pazopanib in this clinical context is not planned.

PMID:40902132 | DOI:10.1200/JCO-24-02644

Eur J Prev Cardiol. 2025 Sep 3:zwaf573. doi: 10.1093/eurjpc/zwaf573. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The most recent guidelines from the European Society of Cardiology (ESC) categorize blood pressure (BP) into three groups: (1) non-elevated BP, (2) elevated BP and (3) hypertension. This study aimed to determine whether the 2024 guidelines from the ESC for elevated BP and hypertension accurately identify populations at increased risk of future cardiovascular diseases.

METHODS: In a population-based cohort derived from the Korean National Health Insurance Service database, we included individuals aged ≥40 years who underwent national health examinations in 2009. Those with a history of stroke or myocardial infarction were excluded. Multivariable Cox proportional hazards models were used to assess the association between blood BP categories and the risk of the composite outcome (stroke, myocardial infarction, and all-cause mortality). Risk estimates based on the 2023 European Society of Hypertension (ESH) classification were also analyzed to illustrate differences in categorization.

RESULTS: A total of 2,604,340 participants were included in the final analysis, with a mean follow-up duration of 11.66 ± 2.25 years. Compared to the non-elevated BP group, both the elevated BP and hypertension groups showed significantly higher risks for the composite outcome (adjusted hazard ratio [aHR] 1.072 (95% CI: 1.059-1.084) and 1.201 (95% CI: 1.186-1.217)). The risks of stroke, myocardial infarction, and all-cause mortality were likewise significantly elevated in both the elevated BP and hypertension groups, respectively. Applying both the ESC and ESH frameworks demonstrated how differing BP thresholds can result in variation in risk assessment across population subgroups.

CONCLUSIONS: Elevated BP and hypertension, as defined by the 2024 ESC guidelines, were associated with increased risk of future cardiovascular events. While findings were directionally consistent with the 2023 ESH classification, the ESC framework identified a broader at-risk population. These results indicate that individuals with elevated BP, as defined by the 2024 ESC classification, have a modestly higher risk of cardiovascular events, particularly ischemic stroke, compared with those with non-elevated BP.

PMID:40902101 | DOI:10.1093/eurjpc/zwaf573