Category: Nevin Manimala

Toxicol Sci. 2026 Jul 30:kfag094. doi: 10.1093/toxsci/kfag094. Online ahead of print.

ABSTRACT

We previously described an integrated in vitro liability assay for seizure, a new approach methodology (NAM) to reduce toxicity due to central nervous system (CNS) liability in drug discovery and development. Here we report the development of SAR (structure activity relationships) to guide drug design away from this liability. SAR test compounds were selected from the Enamine REadily AccesibLe (REAL) database using pharmacophore features and similarity to previous test compounds (amoxapine, diphenhydramine, quetiapine, 4-AP, linopirdine) or to ion channel positive reference compounds (bepridil, NS1619, quinidine, verapamil, XE991). These 88 compounds (10 parent compounds and 78 structurally related derivatives) were screened by automated electrophysiology in cell lines expressing human KV2.1, NaV1.2, the α1β2γ2 GABAA or α4β2 nicotinic receptors to generate IC50 values. Across all four ion channels, the derivative compounds exhibited increased, equivalent or reduced potency compared with the parent compounds, providing a complex and rich dataset for SAR. Regarding individual pharmacophoric features, statistical analysis identified 12 features significantly associated with activity at the α4β2 nicotinic receptor; 4 of these were also significantly associated with activity at KV2.1. Selected parent compounds (amoxapine, diphenhydramine, quetiapine) and structural analogues were screened for seizure-like activity in human induced pluripotent stem cell neurons using microelectrode array. The seizure-like phenotype was altered with the derivatives, as expected from the respective ion channel IC50 values. These data provide insight into specific substructures associated with seizure-like drug toxicity, offering the opportunity to avoid CNS liability in the development of novel compounds, saving time, money and resources.

PMID:42530889 | DOI:10.1093/toxsci/kfag094

Prim Care Companion CNS Disord. 2026 Jul 23;28(4):26m04192. doi: 10.4088/PCC.26m04192.

ABSTRACT

Objective: Internet gaming disorder (IGD) has gained increasing global recognition, yet little is known about how health care providers perceive and manage this condition in clinical practice. The objective of this study was to assess health care providers’ IGD-related beliefs, familiarity with diagnostic criteria, confidence in diagnosis and management, and perceived training needs.

Methods:A cross-sectional online survey of internal medicine and psychiatry health care providers was conducted between September and October 2025 at a large academic medical center, assessing IGD-related beliefs, familiarity with diagnostic criteria, confidence in diagnosis and management, and perceived training needs.

Results: Among 67 respondents, most participants endorsed IGD as a clinically significant condition (84%) that contributes to psychiatric comorbidities (87%). However, fewer than half of providers reported confidence diagnosing (44%) or managing IGD (29%), and only 37% were familiar with currently proposed Diagnostic and Statistical Manual of Mental Disorders criteria. Psychiatric health care providers reported greater confidence and familiarity with IGD than their internal medicine counterparts, particularly in diagnosis, management, and identification of diagnostic criteria during clinical encounters. Overall, 81% of participants indicated that they would benefit from additional IGD-related education.

Conclusion: Despite broad recognition of IGD’s clinical significance, substantial gaps remain in provider confidence and familiarity with diagnostic and management approaches, particularly outside of psychiatry. These findings identify actionable gaps in provider preparedness and highlight the need for targeted educational efforts to support effective clinical management of IGD across medical specialties.

Prim Care Companion CNS Disord 2026;28(4):26m04192.

Author affiliations are listed at the end of this article.

PMID:42530875 | DOI:10.4088/PCC.26m04192

Prim Care Companion CNS Disord. 2026 Jul 21;28(4):26m04184. doi: 10.4088/PCC.26m04184.

ABSTRACT

Objective: To adapt the Borderline Symptom List 23 (BSL-23) to Brazilian Portuguese and evaluate its psychometric properties in a large nonclinical sample.

Methods: A total of 2,682 participants completed an online questionnaire between December 2021 and January 2022. Participants had a mean age of 26.64 years; most were female (78.2%) and had completed higher education. The adaptation process followed established guidelines, including translation, back-translation, expert evaluation, and target-population review. In addition to the BSL-23, participants completed the Depression, Anxiety and Stress Scale-21 Items (DASS-21), Difficulties in Emotion Regulation Scale (DERS), Barratt Impulsiveness Scale, and Childhood Trauma Questionnaire. Statistical analyses included exploratory and confirmatory factor analyses, internal consistency assessment, and tests of concurrent validity and measurement invariance.

Results: The BSL-23 maintained a unidimensional structure and demonstrated excellent internal consistency (Cronbach α=0.95). Exploratory factor analysis indicated high factor loadings for most items, while confirmatory factor analysis required minor adjustments due to collinearity between certain item pairs. Measurement invariance analyses showed small but statistically significant gender differences with minimal practical impact. Concurrent validity was supported by strong correlations with DASS-21 stress and depression subscales and moderate correlations with DERS dimensions.

Conclusion: The Brazilian Portuguese version of the BSL-23 demonstrated robust psychometric properties, confirming its validity for use in Brazilian samples. Future studies should include clinical populations and assess test-retest reliability to strengthen evidence of temporal stability.

Prim Care Companion CNS Disord 2026;28(4):26m04184.

Author affiliations are listed at the end of this article.

PMID:42530867 | DOI:10.4088/PCC.26m04184

Acta Neurol Belg. 2026 Jul 30. doi: 10.1007/s13760-026-03113-w. Online ahead of print.

ABSTRACT

BACKGROUND: Neuromodulation therapies, including vagus nerve stimulation (VNS), anterior nucleus of the thalamus deep brain stimulation (ANT-DBS), and responsive neurostimulation (RNS), have become established treatments for drug-resistant epilepsy. While seizure outcomes have been well-characterized, the long-term neuropsychiatric consequences of these interventions remain incompletely understood. This review aimed to compile available evidence on depression, anxiety, cognitive function, and quality of life following chronic neuromodulation therapy in adults and children with epilepsy.

METHODS: We conducted a systematic search of PubMed, EMBASE, the Cochrane Library, and PsycINFO from inception through September 2025. Studies reporting neuropsychiatric outcomes after at least six months of VNS, ANT-DBS, or RNS therapy in patients with epilepsy were eligible. Random-effects meta-analysis was performed using standardized mean differences (SMDs). Heterogeneity was assessed via Cochran Q and I-squared statistics. Publication bias was evaluated with funnel plots and Egger regression.

RESULTS: From 2,847 records screened, 35 studies met inclusion criteria and 24 contributed to quantitative synthesis, encompassing 2,418 patients. The pooled effect on depression was a small but statistically significant improvement (SMD = -0.25; 95% CI: -0.43 to -0.07; p = 0.007). Subgroup analysis showed VNS had the largest antidepressant effect (SMD = -0.40; 95% CI: -0.69 to -0.10), while ANT-DBS (SMD = -0.18; 95% CI: -0.50 to 0.15) and RNS (SMD = -0.14; 95% CI: -0.47 to 0.19) showed non-significant trends toward improvement. Cognitive outcomes remained largely stable across all modalities, with no significant decline in overall cognitive performance (VNS: SMD = 0.07; DBS: SMD = 0.05; RNS: SMD = 0.02). Quality of life improved progressively, with clinically meaningful gains observed by the second year of treatment across modalities. Neuropsychiatric adverse events were most frequent in the ANT-DBS group, where 14.8% reported depressive symptoms during the blinded phase of the SANTE trial, though these diminished substantially over long-term follow-up.

CONCLUSIONS: Neuromodulation for drug-resistant epilepsy is associated with modest improvements in depression and quality of life without meaningful cognitive deterioration over follow-up durations of 6 months to 14 years. VNS demonstrated the most robust antidepressant signal, likely reflecting its established effects on monoaminergic brainstem circuits. Clinicians should monitor neuropsychiatric status, particularly during the early postimplantation period for ANT-DBS. Earlier intervention may optimize mood and quality of life benefits.

PMID:42530840 | DOI:10.1007/s13760-026-03113-w

Community Ment Health J. 2026 Jul 30. doi: 10.1007/s10597-026-01664-z. Online ahead of print.

ABSTRACT

Faith and spirituality have long been recognized as important components of recovery from mental illness, yet little is known about how these experiences evolve over time or the extent to which individuals feel supported by mental health professionals in pursuing them. This study explored how peer support workers’ experiences with spirituality and faith change over time, how they perceive the role of spirituality in their recovery, and how supported they feel by mental health professionals from whom they are receiving care in this aspect of their well-being. The study involved a cross-sectional online survey of 266 peer support workers in the United States, examining their experiences with faith and spirituality. Data were analyzed using paired-sample t-tests and descriptive statistics. Participants reported significantly more positive faith and spiritual experiences in the present compared to the past. Current experiences were largely positive (83%), with 92% reporting that faith/spirituality played a very positive or positive role in their recovery. Nonetheless, challenges persisted, including disagreement with family or friends about religious issues (62%) and feeling lonely or different from others because of religious or spiritual beliefs (40%). While most participants (63%) felt encouraged by healthcare providers to pursue spirituality, fewer than half (45%) reported receiving active support. Findings suggest faith and spirituality are a significant part of recovery for many peer support workers. However, inconsistent provider support underscores the need for more integrated, holistic models of mental health services that acknowledge spirituality as a dynamic, evolving dimension of recovery.

PMID:42530835 | DOI:10.1007/s10597-026-01664-z

Environ Sci Pollut Res Int. 2026 Jul 30. doi: 10.1007/s11356-026-38087-y. Online ahead of print.

ABSTRACT

Advancing air pollution forecasting: a review of physical, statistical, and machine learning methods provides a timely and comprehensive overview of deterministic, statistical, machine learning (ML), and hybrid approaches in air quality modeling. The review effectively summarizes recent developments and highlights emerging trends, such as physics-informed machine learning and integrated forecasting systems. However, several critical operational challenges require further discussion. These include model transferability across data-sparse regions, uncertainty quantification, the interpretability of deep learning architectures, operational robustness, and data quality constraints. Recent advancements in adaptive mesh refinement, AI-assisted chemical transport models, and hybrid deep learning frameworks further underscore the need for explainable, multi-scale, and impact-oriented systems. We argue that future air quality forecasting must move beyond predictive accuracy alone to increasingly integrate atmospheric chemistry, high-resolution observations, rigorous uncertainty analysis, and public health frameworks. Hybrid systems that couple physical interpretability with artificial intelligence represent the most promising frontier for next-generation operational workflows.

PMID:42530833 | DOI:10.1007/s11356-026-38087-y

Environ Sci Pollut Res Int. 2026 Jul 30. doi: 10.1007/s11356-026-38094-z. Online ahead of print.

ABSTRACT

Chronic scarcity of continuous in situ sampling severely hampers trophic monitoring in tropical reservoirs, restricting the application of data-intensive models in regulatory environments. Therefore, the aim of this study was to develop a cross-validation framework integrating a Mamdani Fuzzy Inference System (FIS) with Sentinel-2 Normalized Difference Chlorophyll Index (NDCI) retrievals via Google Earth Engine (GEE) to overcome these limitations. The methods involved parameterizing the FIS with subtropical thresholds using a 16-year limnological dataset from the Billings Reservoir (Brazil). This system was then cross-validated against satellite-derived NDCI distributions using non-parametric statistical tests. Subsequently, it was applied to the Funil Reservoir to evaluate spatial transferability based exclusively on NDCI mapping, without concurrent in situ validation. The results demonstrated a statistically significant validation at the Billings Reservoir (Kruskal-Wallis, p < 0.05 ), confirming that NDCI medians vary systematically across fuzzy-classified trophic states. Additionally, Levene’s test revealed homogeneous variance for total phosphorus (TP) ( W = 3.09 , p = 0.051 ) contrasting with heteroscedastic chlorophyll-a (Chl-a) ( p < 0.05 ), characterizing the distinct dispersion regimes of eutrophication drivers and biological responses. Furthermore, the NDCI-based application to the Funil Reservoir yielded synoptic maps that indicated potential algal bloom expansion at resolutions unattainable by conventional monitoring. In conclusion, this approach establishes remote sensing-based surveillance via NDCI, initially calibrated by fuzzy logic, as a valuable screening tool for eutrophication monitoring in data-scarce aquatic systems.

PMID:42530831 | DOI:10.1007/s11356-026-38094-z

Adv Ther. 2026 Jul 30. doi: 10.1007/s12325-026-03734-w. Online ahead of print.

ABSTRACT

INTRODUCTION: To evaluate postpartum depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS) and identify demographic, obstetric, and neonatal factors associated with EPDS positivity in women without prior psychiatric history.

METHODS: This retrospective, archive-based multicentre study enrolled 763 women aged 20-35 years who delivered at two public hospitals in Turkey (June 2022-June 2025). Variables included educational attainment, employment, pregnancy planning, mode of delivery, abortion/stillbirth history, preeclampsia, birth weight, and neonatal intensive care unit (NICU) admission. Participants were classified as EPDS < 13 or ≥ 13 at the fourth postpartum week; comparisons used univariable and multivariable logistic regression with Bonferroni adjustment.

RESULTS: Of 763 women, 198 (26.0%) scored ≥ 13. After adjustment and Bonferroni correction, history of abortion and preeclampsia remained statistically significant. Working status and history of stillbirth showed nominal associations before correction but did not remain significant after Bonferroni correction. NICU admission was significant in unadjusted analysis but did not remain significant after adjustment (aOR 1.44, 95% CI 0.80-2.60, p = 0.226).

CONCLUSION: Postpartum depressive symptoms affected one in four women. After adjustment and Bonferroni correction, preeclampsia and history of abortion remained associated with EPDS positivity. Targeted psychological screening may be considered for women with high-risk pregnancy or neonatal complications.

PMID:42530824 | DOI:10.1007/s12325-026-03734-w

Int J Cardiovasc Imaging. 2026 Jul 30. doi: 10.1007/s10554-026-03785-8. Online ahead of print.

ABSTRACT

The Coronary Artery Disease Reporting and Data System (CAD-RADS) standardizes coronary CT angiography (CCTA) reporting, but not all reports contain CAD-RADS classifications. We benchmarked 54 large language model (LLM) configurations across 50 distinct models, including recent proprietary and open-weight reasoning models, for zero-shot CAD-RADS classification. We retrospectively analyzed 500 anonymized CCTA reports from four hospitals across three U.S. regions. Expert cardiovascular radiologists provided the reference standard (human inter-rater [Formula: see text]). Fifty-four model configurations (50 distinct LLMs; four configurable models tested in both thinking and non-thinking modes) spanning Llama 2 7B through recent thinking models (DeepCogito v2, Gemini 3 Pro) processed reports using identical zero-shot prompts. Performance was measured with unweighted Cohen’s κ. Two LLMs met both pre-specified non-inferiority criteria ([Formula: see text] margin and entire 95% CI within the human inter-rater agreement band, [Formula: see text]-0.956): Claude 4.6 Opus ([Formula: see text], 95% CI 0.817-0.889) and the open-weight Gemma 4 31B ([Formula: see text], 95% CI 0.810-0.882), which ranked second overall. Both met the criteria at the pre-specified [Formula: see text] margin; at [Formula: see text] no model qualified. On the reports originally dictated without a CAD-RADS statement (n=343), the top models reached [Formula: see text]. Performance declined with longer thinking chains (proxy for case complexity), but thinking-mode outperformed non-thinking mode on matched difficult reports. Gemma 4 31B remained non-inferior at 3-bit quantization and fits on a 24 GB consumer GPU. Current LLMs extract the CAD-RADS stenosis severity category from unstructured CCTA reports with agreement approaching the human inter-rater band, without task-specific training. Our data shows the remarkable rise of open models. A 31B open-weight model matched top proprietary systems and runs on consumer GPUs, enabling privacy-preserving local deployment for clinical data mining.

PMID:42530821 | DOI:10.1007/s10554-026-03785-8

Updates Surg. 2026 Jul 30. doi: 10.1007/s13304-026-02787-4. Online ahead of print.

NO ABSTRACT

PMID:42530818 | DOI:10.1007/s13304-026-02787-4