Nevin Manimala

JAMA Psychiatry. 2026 Apr 8. doi: 10.1001/jamapsychiatry.2026.0190. Online ahead of print.

ABSTRACT

IMPORTANCE: Ketamine has well-known dissociative, analgesic, and antidepressant properties, but it is unknown whether the neurophysiologic effects that are associated with these properties can be modulated separately from one another. Considering that specific cortical oscillations have been associated with specific therapeutic effects, modulating selective aspects of ketamine neurophysiology could inform efforts to develop more targeted therapies.

OBJECTIVE: To determine whether the neurophysiologic signatures of ketamine are associated with removal of conscious awareness using general anesthesia (GA).

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a secondary analysis of participant-level data from 3 prospective studies conducted between 2017 and 2023. The primary analysis included data from 2 study cohorts (University of Michigan and Stanford University), and the supplementary analysis included data from a third cohort (University of Auckland). The study cohorts included healthy volunteers, patients undergoing elective surgery, and patients with a diagnosis of depression (all aged ≥18 years).

EXPOSURE: Participants received a subanesthetic infusion of ketamine (0.5 mg/kg body weight) over 40 minutes or placebo with or without GA.

MAIN OUTCOMES AND MEASURES: The primary outcome was change in electroencephalographic (EEG) band power during medication infusion. Changes were computed using nonparametric paired statistical text (Wilcoxon signed-rank test).

RESULTS: This study included 52 participants in the primary analysis (mean [SD] age, 43.4 [18.3] years; 34 females [65.4%]) and 27 additional participants in the supplementary analysis (mean [SD] age, 30.2 [8.2] years; 15 females [55.6%]). GA differentially altered EEG features commonly associated with ketamine in all 52 participants (100%) in the primary analysis. Compared with awake administration, ketamine administered during GA preserved its βγ power modulation (mean [SEM] increase from 6.3 [11.3] to 11.6 [2.2] dB for awake administration; increase from 8.5 [2.9] to 11.2 [3.8] dB for administration during GA) but lacked its characteristic θ augmentation (increase from 17.3 [10.5] to 22.9 [3.1] dB during awake administration; nonsignificant decrease from 29.0 [3.0] to 27.8 [3.5] dB for administration during GA).

CONCLUSIONS AND RELEVANCE: In this cohort study, coadministration of ketamine with GA selectively modulated the θ but not the βγ neurophysiologic correlates of ketamine. These findings suggest a potential method to explore the role of these components in the behavioral effects of ketamine.

PMID:41949829 | DOI:10.1001/jamapsychiatry.2026.0190

MAGMA. 2026 Apr 8. doi: 10.1007/s10334-026-01351-w. Online ahead of print.

ABSTRACT

OBJECTIVES: Magnetic resonance spectroscopic imaging (MRSI) is a non-invasive technique for probing metabolism. MRSI enables spatial mapping of metabolite distributions, offering insights into regional metabolic heterogeneity that single-voxel spectroscopy (SVS) cannot capture. However, MRSI produces large multidimensional datasets and requires complex processing pipelines, limiting reproducibility and accessibility. While human studies benefit from advanced processing tools, similar developments in preclinical research remain scarce, highlighting a demand for practical tools accessible to non-experts. Furthermore, recent advances in deuterium-based MRSI have opened metabolic pathway studies, introducing additional dimensions for kinetic information and specific positional labeling, thus substantially increasing dataset complexity and analysis demands.

METHODS: To address these needs, we introduce the MRS4Brain Toolbox, a freely available MATLAB-based platform for preclinical MRSI supporting proton, deuterium, and other nuclei, with extended functionalities for SVS and diffusion-weighted spectroscopy.

RESULTS: The toolbox integrates reconstruction, preprocessing, quantification, quality control, brain segmentation automatically overlaid on metabolite maps, modeling, and statistical analysis into unified workflows accessible via a graphical interface.

CONCLUSION: By streamlining data processing and reducing technical barriers, MRS4Brain Toolbox promotes reproducibility, harmonization, and broader adoption of basic and advanced spectroscopic techniques in preclinical studies, ultimately facilitating translational metabolic research.

PMID:41949812 | DOI:10.1007/s10334-026-01351-w

Shock. 2026 Mar 20. doi: 10.1097/SHK.0000000000002725. Online ahead of print.

ABSTRACT

INTRODUCTION: Calibrated automated thrombography (CAT) assay parameters have been shown to assess hypercoagulation state and, therefore, may independently predict post-trauma, symptomatic venous thromboembolism (VTE). Yet, CAT lacks high throughput and standardization, limiting diagnostic potential. This study analyzed thrombin generation profiles in trauma patients using a high throughput assay, processing up to 10 samples at once, providing batch testing capabilities. We hypothesized that trauma patients who developed VTE would show distinct thrombin generation profiles compared to those who did not.

METHODS: Trauma patients presenting to a Level I Trauma Center had samples collected within 12 hours post-injury prospectively. Follow-up was conducted to 90 days, time to symptomatic VTE diagnosis or death, confirmed via autopsy or imaging. Thrombin generation profiles were measured from the ST Genesia assay. Data was presented as median [IQR] or n (%), with Wilcoxon rank-sum or chi-squared test. Associations between thrombin generation parameters and clinical risk factors were assessed using Spearman correlation analysis or the Wilcoxon rank-sum test.

RESULTS: Two-hundred and fifty-four trauma patients were analyzed (48.5 years [31.0, 62.0], 72.0% male): 64 patients with VTE (25.2%) to 190 with non-VTE. VTE pts had a median time to VTE of 8 days, with 29 developing deep venous thrombosis (DVT), 24 with pulmonary embolism (PE), and 11 with DVT/PEs. No significant differences were found in age, sex, or Body Mass Index (BMI); significantly more VTE patients underwent surgery and blood transfusions within 24 hours. Thrombin generation profiles demonstrated accelerated thrombin generation in patients who developed VTE compared to non-VTE, with significant differences in Peak Height (p=0.001), Time to Peak (p=0.021), Endogenous Thrombin Potential (p<0.001) and Velocity Index (p=0.001).

CONCLUSION: Thrombin generation profiles using ST Genesia can differentiate trauma patients at high risk of developing VTE. The platform suits clinical labs needing high throughput by providing batch testing capabilities.Study Type: Prospective study with less than large effect and no negative criteria.Level of Evidence: II.

PMID:41949808 | DOI:10.1097/SHK.0000000000002725

Ophthalmic Physiol Opt. 2026 Apr 8. doi: 10.1007/s44402-026-00076-6. Online ahead of print.

ABSTRACT

PURPOSE: To refit contact lens (CL) dropouts who dropped out of CLs because of dryness or discomfort into lehfilcon A (TOTAL30®) monthly, spherical CLs to determine the frequency that they can be comfortably refitted into CLs.

METHODS: A 6-month, four-visit, multi-centre, open-label, single-arm, six-site study was conducted in the United States. Adults, 18- to 40-year-old, past CL wearers who dropped out of reusable CLs at least 3 months but not more than 2 years ago because of discomfort or dryness were enrolled. Participants were required to have no significant dry eye symptoms (SPEED scores ≤3). All participants were then fitted into lehfilcon A CLs. The participants were evaluated with the SPEED, a comfort visual analogue scale (VAS; 0-100 scale) and a Likert questionnaire.

RESULTS: This study enrolled 61 participants who had a median (interquartile) age of 28 (7) years (78.7% female). The participants had a right eye median (IQR) refractive error (sphere/cylinder power) of -1.50 D (2.50 D)/-0.50 D (0.50 D). This study had a CL retention rate of 98.4% at 1 month and 65.6% at 6 months. The VAS yielded a median comfort score of 81 (40) at 6 months. The Likert questionnaire found that 80.7% of participants would recommend the CLs to a friend at 6 months. SPEED scores increased statistically after resuming CL wear (p = 0.0001) at 1 month, yet this symptom change was unlikely to be clinically meaningful.

CONCLUSIONS: This study found that previous CL wearers who had dropped out of CLs could be comfortably refitted with lehfilcon A monthly replacement, silicone hydrogel CLs, with most of them continuing to wear the CLs after 6 months of daily wear. The results suggest that the monthly soft CLs with water gradient technology can be a viable option for many CL dropout sufferers.

PMID:41949795 | DOI:10.1007/s44402-026-00076-6

Ophthalmic Physiol Opt. 2026 Apr 8. doi: 10.1007/s44402-026-00058-8. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the effect of nightly 0.01% atropine eye drops on choroidal thickness (ChT) in pre-myopic children (at risk of myopia).

METHODS: In a 12-month randomised, double-blind, placebo-controlled trial, 54 children aged 5-12 received nightly 0.01% atropine or placebo in both eyes. ChT was measured in 15 macular sectors using swept-source OCT at baseline and every 3 months. Longitudinal mixed-effects models (LMM) compared ChT changes between groups, and an unsupervised clustering analysis of individual ChT trajectories was performed.

RESULTS: Both groups showed progressive choroidal thinning. At 12 months, atropine-treated eyes showed a trend towards less choroidal thinning than placebo, especially in the central, inferior and temporal macular areas, but between-group differences did not reach statistical significance after multiple comparison correction. Clustering of ChT trajectories revealed two exploratory clusters: a “Thinning-dominant” pattern with pronounced mid-year thinning (6-9 months) followed by partial recovery by month 12 and a “Stable ChT” pattern with minimal change. Eyes in the Thinning-dominant group had faster axial elongation than the Stable group, suggesting an association between ΔChT clusters and ocular growth.

CONCLUSIONS: Nightly low-dose atropine in pre-myopic children showed a non-significant trend toward reduced macular choroidal thinning. Clustering and early-change analyses revealed heterogeneity in ChT responses and exploratory associations with ocular growth. These findings require external validation and do not support early ΔChT as a clinically actionable treatment-response marker.

PMID:41949791 | DOI:10.1007/s44402-026-00058-8

J Orthop Traumatol. 2026 Apr 8. doi: 10.1186/s10195-026-00917-7. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to evaluate whether the acetabular angle (AA) by Tönnis and lateral center-edge angle (LCEA) by Wiberg-key radiographic parameters in pediatric hip assessment-have changed in a contemporary pediatric population compared with historical reference values, considering trends in earlier skeletal maturation and body composition.

MATERIALS AND METHODS: This retrospective diagnostic accuracy study assessed changes in AA and center-edge angle (CE) angles in a contemporary cohort. A total of 1774 anteroposterior pelvic radiographs (3548 hips) from patients aged 0-18 years without hip pathology were analyzed. Radiographs were obtained between 2006 and 2018 and measured using the Supervisely digital platform. Standardized anatomical landmarks were applied. Data were stratified by age and sex and compared with historical values using two-sample t-tests (p < 0.05). To minimize measurement bias, two independent observers conducted all assessments using standardized digital protocols.

RESULTS: A total of 1774 patients aged 0-18 years (mean age, 8.30 ± 5.20 years; 666 females, 1108 males) were evaluated. AA values did not show statistically significant differences in 11 of 16 age groups compared with historical data (p > 0.05). In contrast, LCEAs were significantly higher in the contemporary cohort, especially in the 5-8, 9-12, and 12-16 age groups (all p < 0.01), indicating a trend toward earlier or increased acetabular ossification and femoral head coverage.

CONCLUSIONS: LCEA values were significantly higher in the contemporary pediatric cohort compared with historical data, while AA values remained stable across most age groups. These findings suggest that current radiographic reference standards for LCEA may warrant reassessment to ensure accurate dysplasia assessment.

LEVEL OF EVIDENCE: level 3 (diagnosis).

PMID:41949745 | DOI:10.1186/s10195-026-00917-7

Phys Eng Sci Med. 2026 Apr 8. doi: 10.1007/s13246-026-01718-2. Online ahead of print.

NO ABSTRACT

PMID:41949742 | DOI:10.1007/s13246-026-01718-2

Indian J Gastroenterol. 2026 Apr 8. doi: 10.1007/s12664-026-01967-9. Online ahead of print.

ABSTRACT

BACKGROUND: Gallbladder cancer (GBC) is the most common biliary tract malignancy and a leading cause for mortality in the Asian sub-continent. The low survival rate is attributed to current invasive diagnostic methods and late-stage disease detection. The aim of this study was to estimate the potential value of miR 183_5p and 3651 as diagnostic blood-based biomarkers in GBC patients.

METHODS: This single center observational study evaluates differential expression of miRNAs in GBC and normal gallbladder tissues via micro-array analysis. The level of selected oncogenic miRNAS were detected in 130 individuals comprising GBC patients, Gallbladder stone (GBS) and healthy controls by using qRT-PCR. The diagnostic value of miR-183-5p and 3651 in GBC was evaluated and compared with the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19.9 (CA 19.9).

RESULTS: As many as 45 differentially expressed microRNAs (p < 0.05) were determined, of which 23 were upregulated and 22 were down regulated. miR 183_5p (2.5-fold) and 3651 (5.6-fold) were significantly over expressed in GBC patients compared to controls (p < 0.05). The area under the curve (AUC) value of miR 183_5p and 3651 for GBC diagnosis was 0.684 and 0.752, respectively, which was more valuable than those including CEA (0.617) and CA19.9 (0.718).

CONCLUSION: Study underscores ability of serum miRNAs 183_5p and 3651 as diagnostic biomarkers for early GBC detection.

PMID:41949739 | DOI:10.1007/s12664-026-01967-9

Environ Monit Assess. 2026 Apr 8;198(5):417. doi: 10.1007/s10661-026-15276-3.

ABSTRACT

Urban air pollution remains a critical environmental challenge in rapidly growing Southeast Asian tropical coastal cities. This 5-year air quality monitoring analysis investigates long-term trend patterns and meteorological influences on major air pollutants (PM₁₀, PM_2.5, SO₂, CO, NO₂, and O₃) in Padang, Indonesia, using continuous observations from 2019 to 2023. Long-term trend analysis based on the Mann-Kendall test indicates significant increasing trends in combustion-related pollutants, particularly CO (+311.5 µg m⁻³ yr⁻¹, p < 0.001) and NO₂ (+2.34 µg m⁻³ yr⁻¹, p < 0.05), whereas O₃ exhibits a significant long-term monotonic decreasing trend (-8.67 µg m⁻³ yr⁻¹, p < 0.01), despite seasonal and episodic increases observed during dry and post-pandemic periods. CO and NO₂ showed positive associations with high solar radiation and pressure and negative associations with precipitation, indicating pollutant accumulation under hot and dry conditions. Conversely, particulate matter demonstrated weak long-term trends but clear wet-scavenging influences. Seasonal monsoon variability and atmospheric stagnation appear to play important roles in shaping pollutant variability. These findings highlight the importance of integrating meteorological influence into air quality management strategies in tropical coastal cities.

PMID:41949715 | DOI:10.1007/s10661-026-15276-3

Clin Rheumatol. 2026 Apr 8. doi: 10.1007/s10067-026-08098-8. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the impact of fear-avoidance beliefs, anxiety, and depression on disease activity in patients with ankylosing spondylitis (AS), focusing on pain as a mediator and exercise as a moderator.

METHODS: This cross-sectional study included 77 AS patients. We assessed disease activity using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), pain via Visual Analog Scale (VAS), anxiety and depression with the Hospital Anxiety and Depression Scale (HADS), and fear-avoidance beliefs. We controlled for key covariates including age, gender, disease duration, functional status (HAQ), and medication use (biologic agents, antidepressants). Advanced statistical analyses included bootstrapped mediation (5,000 samples), moderated mediation, tenfold cross-validation, and robustness checks.

RESULTS: Abnormal anxiety (HADS-A ≥ 8) was present in 27.3% and abnormal depression (HADS-D ≥ 8) in 13.0% of patients. Pain was found to be a significant mediator in the pathway between fear-avoidance and BASDAI. The unstandardized indirect effect was 0.265 (95% CI [0.129, 0.446]), accounting for 49.1% of the total effect. This indirect pathway was significantly moderated by exercise, with the effect being stronger in low exercisers compared to high exercisers. A prediction model for high disease activity demonstrated strong discriminative ability (AUC = 0.863) with minimal overfitting confirmed by cross-validation (cross-validated AUC = 0.816).

CONCLUSION: Psychosocial factors are significant predictors of disease activity in AS. Our findings suggest that pain mediates the association between fear-avoidance beliefs and disease activity, a pathway that appears to be attenuated by regular exercise. These findings support a biopsychosocial approach in AS management. Future longitudinal studies are needed to confirm causal pathways. Key Messages • Fear-avoidance beliefs, assessed via a brief screening measure, are associated with disease activity in ankylosing spondylitis. • Pain partially mediates the relationship between fear-avoidance and disease activity, a pathway that is weakened by regular exercise. • Psychosocial screening and targeted interventions should be integrated into standard AS management.

PMID:41949713 | DOI:10.1007/s10067-026-08098-8