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Integrated transcriptomic and metabolomic analyses provide new insights into the response of black rockfish (Sebastes schlegelii) larvae to temperature fluctuations.

Sebastes schlegelii usually encounter elevated and fluctuating water temperatures near its upper thermal limit in summer, yet the hepatic responses of larvae to repeated temperature fluctuation regimes remain unclear. To address this question, S. schlegelii larvae were exposed for 8&#xa0;days to four thermal regimes: constant 18&#xa0;&#xb0;C (CT), constant 28&#xa0;&#xb0;C (HT), intermittent cooling from 18 to 8&#xa0;&#xb0;C followed by recovery to 18&#xa0;&#xb0;C (FL), and intermittent warming from 18 to 28&#xa0;&#xb0;C followed by recovery to 18&#xa0;&#xb0;C (FH). Survival rate was evaluated, and integrated liver transcriptomic and metabolomic analyses were performed. Final survival rates were 96.67% in the CT group, 97.78% in the FL group, and 77.78% in the FH group. Survival rate in the HT group (38.89%) was significantly lower than that in the other three groups (P&#xa0;<&#xa0;0.05). HTvsCT, FLvsCT, FHvsCT, and FHvsHT comparisons identified 2598, 1207, 622, and 2404 differentially expressed genes and 627, 606, 690, and 610 differential metabolites, respectively. KEGG enrichment analyses of DEGs and SDMs in HTvsCT highlighted HSP-mediated proteostasis, endoplasmic-reticulum protein processing, branched-chain and sulfur amino acid metabolism, glutathione metabolism, and central carbon metabolism, with upregulated hsp90aa1, bckdha, gclc, and pfkp and reduced levels of branched-chain amino acids and methionine. Compared with HT, FH showed attenuated disturbances in proteostasis, amino acid and redox regulation, and central carbon metabolism, together with recovery-associated glycerophospholipid turnover. FL primarily induced polyunsaturated fatty acid (PUFA)-related membrane lipid remodeling. These findings indicate that hepatic responses differed between continuous high-temperature exposure and temperature fluctuations and between fluctuation regimes.

Animals

Excess iodine induces lipid metabolic disorders by the gut microbiota SCFAs/H2S-p-AMPK&#x3b1;/PPAR&#x3b3;/SREBP-1c pathway in female rats.

With the development of living standards, the problem of excess iodine has long been overlooked. This study aimed to investigate the detrimental effects of long-term excess iodine exposure on lipid metabolism in female Sprague-Dawley rats from the gut-liver axis perspective, and to elucidate the underlying molecular mechanisms by which the gut microbiota and its metabolites mediate iodine-induced lipid metabolic disorders. The results indicated that abnormal iodine nutrition has a negative effect on the health of rats. Specifically, excess iodine not only causes thyroid disorders but also leads to liver lipid metabolism disorders, including elevated serum and hepatic total cholesterol/triglyceride levels and lipid accumulation in the liver. Further investigation revealed that excess iodine causes liver lipid metabolism disorders by altering the gut microbiota, which resulted in an increase in the relative abundance of Desulfovibrio and Lachnospiraceae NK4A136_group, and a decrease in the relative abundance of Akkermansia and Blautia in excess iodine groups. A decrease in the relative abundance of Blautia and an increase in Lachnospiraceae NK4A136_group were strongly correlated with reductions in short-chain fatty acids (acetic, propionic, and valeric acids), whereas an increase in Desulfovibrio was strongly correlated with an increase in H2S. Additionally, acetic acid was negatively correlated with H2S in serum and liver. Excess iodine reduced hepatic p-AMPK&#x3b1; expression while upregulating key regulators of lipid metabolism, including SREBP-1c, PPAR&#x3b3; and ACC1. These changes may represent one of the key mechanisms by which excess iodine induces lipid metabolism disorders through the microbiota-metabolite axis. Overall, these findings suggest that excess iodine influences lipid metabolism through the gut-liver axis. The results of this study provide scientific references and guidance for the appropriate intake of iodine and offer novel insights for early nutritional interventions targeting lipid metabolism disorders.

Journal Article

Comparison of Iodinated Contrast Doses Based on Total Body Weight and Lean Body Weight in Pediatric Patients: Impact on Image Quality and Contrast Exposure.

INTRODUCTION: Iodinated contrast dosing in pediatric computed tomography (CT) traditionally relies on total body weight (TBW), which may result in excessive contrast administration, particularly in patients with higher adiposity. Lean body weight (LBW)-based protocols have shown promise in adults but remain underexplored in children. Therefore, the aim of this study was to compare contrast volume requirements and hepatic enhancement quality among three dosing protocols: LBW-based, TBW-based, and the Control Group (CG), based on the institutional standard for pediatric abdominal CT. METHODS: This prospective study enrolled 66 patients (age 0-16 years) undergoing contrast-enhanced abdominal CT between September 2023 and August 2024. Patients were randomly assigned to receive iodinated contrast (iobitridol 350mg I/mL) dosed by: (1) LBW (0.63 g iodine/kg x LBW, calculated using Peters formula; n = 23), (2) TBW (0.46 g iodine/kg x TBW; n = 20), or (3) institutional control protocol (2 mL/kg x TBW, equivalent to 0.7 g iodine/kg; n = 23). Kruskal-Wallis, ANOVA, Two-way ANOVA, ANCOVA, Scheirer-Ray-Hare, and Cohen's Kappa tests with Likert scale were used. RESULTS: The LBW group received lower median contrast volumes (27 mL; IQR, 10-80 mL) compared to the TBW group (34.5 mL; IQR, 18-78 mL) and the CG group (40 mL; IQR, 13-80 mL), although the differences did not reach statistical significance (P > 0.05). Notably, this reduction did not compromise hepatic enhancement, which remained comparable to the CG (552 &#xb1; 139 HU; P = 0.107). CONCLUSION: Lean body weight may be a useful parameter for estimating contrast dose in pediatric abdominal CT, potentially reducing administered volumes without compromising diagnostic image quality. IMPLICATIONS FOR PRACTICE: These results provide early evidence that LBW-based dosing may support more individualized contrast administration in pediatric CT, potentially reducing exposure-related risks.

Humans

Naltrexone Is Superior to Placebo for Abstinence and Craving Reduction in Alcohol-Associated Cirrhosis: NAL-CI Trial.

BACKGROUND AND AIMS: Alcohol use disorder (AUD) coexisting with cirrhosis carries high morbidity and mortality, with no approved pharmacotherapy for AUD. We evaluated the safety and efficacy of naltrexone, an opioid receptor antagonist, in patients with compensated alcohol-associated cirrhosis (AaC) and AUD. METHODS: One hundred patients with compensated AaC and DSM-5 AUD were randomised 1:1 to naltrexone (50&#x2009;mg/day) or placebo for 12&#x2009;weeks. The primary endpoint was point-prevalence abstinence at 12&#x2009;weeks, defined as no alcohol use in the four preceding weeks. Secondary endpoints included craving (Obsessive Compulsive Drinking Scale [OCDS]-Obsessive and Compulsive subscales), lapses, relapses, and hepatic safety. Standardised psychosocial support was provided to both arms. RESULTS: Baseline characteristics were well matched between groups (mean MELD 12.6 vs. 12.7; CTP score 5.9 vs. 6.2; age 42.9 vs. 44.3&#x2009;years). AUDIT and OCDS scores were comparable between groups. Abstinence at 12&#x2009;weeks was significantly higher with naltrexone: 64% (32/50) versus 22% (11/50), p&#x2009;<&#x2009;0.001; OR 10.86 (95% CI: 1.89-62.2). Naltrexone significantly reduced lapses at 3&#x2009;months (28% vs. 54%, p&#x2009;=&#x2009;0.008) and showed a trend toward fewer heavy-drinking relapses (12% vs. 28%, p&#x2009;=&#x2009;0.07). Maintenance of abstinence at 6&#x2009;months favoured naltrexone (22% vs. 8%, p&#x2009;=&#x2009;0.09). No patient developed hepatic decompensation attributable to study medication, and no AST/ALT elevation exceeding 5&#xd7; ULN was observed in either group. Mean craving scores were lower with naltrexone by week 12 than with placebo: OCDS-O score (6.63&#x2009;&#xb1;&#x2009;1.16 vs. 9.29&#x2009;&#xb1;&#x2009;1.78, p&#x2009;<&#x2009;0.01) and OCDS-C score (6.35&#x2009;&#xb1;&#x2009;1.23 vs. 9.02&#x2009;&#xb1;&#x2009;1.86, p&#x2009;<&#x2009;0.01). Adverse events were comparable between the groups. CONCLUSION: Naltrexone is safe and effective in patients with compensated alcohol-associated cirrhosis, achieving a threefold higher abstinence rate and significantly reducing craving compared with placebo. These findings support the use of naltrexone as a pharmacological option in patients with compensated AaC and AUD. TRIAL REGISTRATION: NCT04391764.

Humans

Associations Between Paternal Pre-Conceptional Body Mass Index and Lifestyle Factors and Offspring Weight Development.

BACKGROUND: Evidence suggests that pre-conceptional paternal factors, including BMI and diet, may influence offspring development. OBJECTIVES: We examined the associations between paternal BMI, dietary protein intake, glycemic index (GI), smoking and alcohol consumption and offspring development during the first 5&#x2009;years of life. METHODS: This secondary analysis of an RCT included 162 father-child pairs from pregnancies among women with pre-pregnancy overweight or obesity. Paternal characteristics were reported at gestational week 15, reflecting the preceding 3&#x2009;months. Offspring anthropometry was measured at birth, 6 and 18&#x2009;months, 3 and 5&#x2009;years. Associations were examined using linear mixed models and linear regression models. RESULTS: No consistent associations were found between paternal characteristics and offspring outcomes from birth to 3&#x2009;years. At age 5, higher paternal BMI was associated with higher offspring BMI z-score (&#x3b2;&#x2009;=&#x2009;0.07 (CI: 0.03; 0.10)), fat mass index (&#x3b2;&#x2009;=&#x2009;0.07&#x2009;kg/m2 (CI: 0.02; 0.12)) and fat-free mass index (&#x3b2;&#x2009;=&#x2009;0.05&#x2009;kg/m2 (CI: 0.01; 0.08)). Lower paternal protein intake was associated with higher offspring BMI z-score (&#x3b2;&#x2009;=&#x2009;0.54 (CI: 0.07; 1.01)) and fat-free mass index (&#x3b2;&#x2009;=&#x2009;0.60&#x2009;kg/m2 (CI: 0.13; 1.07)), while moderately higher protein intake was associated with higher waist-to-height ratio (&#x3b2;&#x2009;=&#x2009;0.03 (CI: 3.00&#x2009;&#xd7;&#x2009;10-3; 0.05)). Higher paternal GI was associated with lower offspring BMI z-score (&#x3b2;&#x2009;=&#x2009;-0.04 (CI: -0.08; -2.14-10-3)) at age 5. Smoking and alcohol were not associated with offspring outcomes. CONCLUSION: Paternal BMI was associated with offspring outcomes at age 5&#x2009;years, while findings for paternal dietary factors were less consistent.

Humans

Carboxyl group number and acidity of organic acids regulate structural reorganization and low glycemic index in cassava pyrodextrins via molecular interactions.

Transforming high-glycemic cassava starch into functional dietary fiber via pyrodextrinization is a promising way to valorize tuber crops, yet the molecular mechanisms catalyzed by organic acids with different carboxyl numbers and acidity remain unclear. This study investigates how carboxyl number and acidity of acetic acid (AA), tartaric acid (TA), and citric acid (CA) affect structural reorganization and low glycemic properties of cassava pyrodextrins. Compared with AA, TA, and CA with stronger acidity and more carboxyl groups promoted more extensive hydrolysis, transglycosylation, repolymerization, and esterification. These changes increased indigestible glycosidic linkages and the branching degree, while reducing molecular weight. Molecular docking confirmed stronger hydrogen-bonding interactions between TA/CA and starch chains. Furthermore, TA- and CA-catalyzed pyrodextrins exhibited superior anti-digestive properties with resistant starch up to 54.26% and an estimated glycemic index as low as 42.46, highlighting the critical role of carboxyl numbers and acidities in modulating the functionality of pyrodextrins.

Manihot

Impact of a CARE-ORIENT Education Program on Oral Hygiene Among Institutionalized Older Adults: A Double Blinded Cluster Randomized Controlled Study.

BACKGROUND: Older adults residing in long-term care facilities often depend on caregivers for daily oral care. Inadequate caregiver training may contribute to poor plaque control and denture hygiene. METHODS: A six-month parallel-arm cluster randomized controlled study was conducted in selected long-term care facilities in Northern India. Two old age homes were randomly selected, with one allocated to the intervention group and the other to the control group. A total of 150 older adults and 46 caregivers participated. Caregivers in the intervention group received a structured caregiver oriented oral health education. Clinical assessments were performed at baseline, 3 and 6 months. Outcomes included Debris Index, Turesky-Gilmore-Glickman Plaque Index, Denture Plaque Index and Denture Stomatitis Index. Caregiver knowledge and practice were evaluated using a validated questionnaire. RESULTS: Caregiver knowledge and practice scores improved significantly in the intervention group at 3 and 6 months. Significant differences were observed in Debris Index (DI), Plaque Index (PI), and Denture Plaque Index (DPI) in the intervention group over the six-month follow-up (p < 0.001). The Debris Index decreased from 2.76 &#xb1; 0.07 at baseline to 1.54 &#xb1; 0.05 at 6 months. Plaque Index scores declined from 3.26 &#xb1; 0.06 to 1.85 &#xb1; 0.08, and Denture Plaque Index scores reduced from 3.22 &#xb1; 0.03 to 1.74 &#xb1; 0.05. Denture Stomatitis Index improved over time; however, intergroup differences were not statistically significant. CONCLUSION: Structured caregiver-focused oral health education significantly improved oral hygiene among institutionalized older adults over six months, supporting integration of caregiver training within routine long-term care.

Humans

The relationship between composite dietary antioxidant index and odds of depression: A systematic review and dose-response meta-analysis of observational studies.

BACKGROUND: Recently, the association between the composite dietary antioxidant index (CDAI) score and depression has received special attention from researchers. However, this possible association has not been comprehensively examined. Thus, the present study aims to comprehensively assess the relationship between CDAI score and depression odds. METHODS: A thorough literature search was performed using Scopus, PubMed, and Web of Science up to November 2025. Observational studies assessing the relationship between CDAI score and depression odds were included. The odds ratios (ORs) and their 95% confidence intervals (CIs) reported in each study were extracted, and a pooled effect size was calculated using a random-effects model with inverse-variance weighting. RESULTS: Four observational studies were included in the current systematic review and meta-analysis. The pooled effect size indicated that a higher CDAI score was associated with lower odds of depression (OR:0.62; 95%CI: 0.51-0.76, I2&#xa0;=&#xa0;48.5%; P-value&#xa0;=&#xa0;0.121). In an exploratory linear dose-response analysis based on two eligible studies, no significant association was observed between a one-unit increase in CDAI score and the odds of depression (OR&#xa0;=&#xa0;0.96; 95% CI: 0.91-1.02; I2&#xa0;=&#xa0;92.2%; P-value<0.001). Given the limited number of studies and substantial heterogeneity, these findings should be interpreted cautiously. CONCLUSIONS: Our findings suggest that higher CDAI scores, reflecting greater adherence to antioxidant-rich dietary patterns, are associated with lower odds of depression.

Humans

Effect of SGLT2 inhibitor drugs on triglyceride-glucose (TyG) index in adults: A systematic review and meta-analysis.

BACKGROUND: Insulin resistance is a serious public health concern. The triglyceride-glucose (TyG) index is a simple, cheap, and reproducible surrogate of insulin resistance, and sodium-glucose cotransporter-2 (SGLT2) inhibitors have reshaped cardio-metabolic care beyond glycemic control. METHODS: We followed PRISMA and registered the protocol in PROSPERO (CRD420251056341). We searched PubMed, Scopus, Web of Science, EMBASE, and Cochrane from inception to May 31st, 2026, including observational studies and clinical trials reporting baseline and follow-up TyG in adults. Two reviewers screened records, a third resolved disagreements, data were extracted with a standardized form, and quality was assessed with Cochrane RoB 2.0, the Newcastle-Ottawa Scale, and the JBI checklists. The primary outcome was within-group change in TyG pooled with random-effects (Hartung-Knapp); tests were two-sided with a significance threshold of 0.05. RESULTS: Twelve studies comprising thirteen study arms were included, with a total of 1845 participants. Follow-up ranged from 12 weeks to 5 years. Across studies, SGLT2 inhibitor therapy was associated with a significant reduction in TyG index (mean difference = -0.28, 95% confidence interval [-0.41; -0.14], I2 = 99.5%). Egger's test suggested possible small-study effects, whereas Begg's test and trim-and-fill analysis did not show clear evidence of publication bias; leave-one-out analyses showed that no single study materially influenced the pooled estimate. CONCLUSION: Despite heterogeneity in populations, drug choice, and follow-up duration, SGLT2 inhibitors were associated with a significant decrease in TyG, although small-study effects cannot be excluded.

Humans

Vegan multinutrient supplementation significantly increases Omega-3 index and 25-OH-vitamin D status: a randomized, double-blind, placebo-controlled trial in healthy young vegans.

In this randomized, double-blind, placebo-controlled trial, 72 healthy vegan adults (aged 19-57 years) received a multinutrient supplement consisting of a vitamin and mineral supplement (providing 26 &#xb5;g vitamin D) and an omega-3 supplement administered in either a single dose (EPA 98.7 mg, DHA 171.0 mg, additional vitamin D 36 &#xb5;g, vitamin E 3.7 mg) or a double dose (EPA 197.4 mg, DHA 342.0 mg, additional vitamin D 72 &#xb5;g, vitamin E 7.4 mg) or placebo capsules for 4 months. Nutrient biomarkers were assessed at baseline and at the end of the intervention after 4 months. An analysis of covariance was employed to test for between-group differences (p < 0.05) and adjusted for multiple testing using the Bonferroni-Holm method. Compared to the control group, which showed on average a significant decline in both the omega-3-index and 25-hydroxyvitamin D, participants in both intervention groups demonstrated significant increase in these parameters (p < 0.001). Although the double dose group exhibited numerically greater increases in omega-3 index and vitamin D compared to the simple dose group, the differences between these dosing regimens were not statistically significant. As expected, vitamin E levels remained unchanged, reflecting its inclusion solely for antioxidative protection in the omega-3 supplement rather than as a critical nutrient in vegan diets. In conclusion, supplementation significantly improved omega-3 and vitamin D status in healthy vegans, with no significant benefit from doubling the dose. Although clinical endpoints were not evaluated, improved nutrient status may have potential implications for health. The study has been registered at the German Clinical Trials Register (DRKS00028151).

Humans

Validation of the lung immune prognostic index in extensive-stage small cell lung cancer: Post hoc analysis of the caspian and IMpower133 phase 3 trials.

BACKGROUND: The Lung Immune Prognostic Index (LIPI) is an inflammation-based biomarker associated with outcomes to immunotherapy across several tumor types. Its prognostic value in extensive-stage small-cell lung cancer (ES-SCLC), however, remains insufficiently validated. We aimed to validate the prognostic impact of LIPI in ES-SCLC using data from two phase III trials. METHODS: Patients enrolled in the CASPIAN (NCT03043872) and IMpower133 (NCT02763579) trials were included. LIPI groups were defined as good (dNLR<3 and LDH<ULN), intermediate (dNLR&#x2265;3 or LDH&#x2265;ULN) and poor (dNLR&#x2265;3 and LDH&#x2265;ULN). Overall survival (OS) and progression-free survival (PFS) were assessed across LIPI categories and treatment arms. RESULTS: LIPI was available for 1140 patients (Good: 34%, Intermediate: 49%, Poor: 17%), including 708 treated with chemotherapy-immunotherapy and 432 with chemotherapy alone. Poor LIPI was associated with unfavorable characteristics, including lower albumin levels and higher rate of liver metastases. Median OS was 14.6 months (95%CI: 12.4-15.9) for LIPI Good, 10.9 (10.1-11.5) for Intermediate, and 8.4 (7.1-9.3) for Poor (p&#x202f;<&#x202f;0.0001). In multivariate models adjusted on gender, age, ECOG, treatment arm and metastatic sites, LIPI remained an independent prognostic factor for OS (HR Poor vs. Good: 1.76, 95%CI: 1.45-2.15, p&#x202f;<&#x202f;0.001) and PFS (HR: 1.59, 95%CI: 1.33-1.90, p&#x202f;<&#x202f;0.001). Although patients with poor LIPI derived limited benefit from immunotherapy, no significant treatment-LIPI interaction was observed. CONCLUSION: This large post hoc analysis confirms LIPI as a robust and clinically applicable prognostic biomarker in ES-SCLC. Patients with poor LIPI have substantially worse outcomes and limited benefit from immunotherapy, highlighting the need for novel therapeutic strategies in this subgroup.

Humans

Angiography-Based Index of Microcirculatory Resistance in Assessing the MVO and Infarct Size in STEMI Patients.

OBJECTIVES: To evaluate angiography-based index of microcirculatory resistance (angio-IMR) in assessing microvascular obstruction (MVO) and infarct size (IS) in ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The effect of thrombolysis on post-percutaneous coronary intervention (PCI) angio-IMR, and its associations with MVO and IS remains unclear. METHODS: One hundred twenty-three STEMI patients randomized to receive 5&#x2009;mg intravenous bolus of recombinant staphylokinase (r-SAK) or normal saline (NS) before PCI were recruited. Angio-IMR was computed in infarct-related arteries. MVO and IS were detected by cardiac magnetic resonance imaging. RESULTS: Compared with NS group, r-SAK group exhibited numerically lower post-PCI angio-IMR (39.12 U vs. 42.57 U; p&#x2009;=&#x2009;0.567), MVO (54.0% vs. 70.9%; p&#x2009;=&#x2009;0.059), MVO extent (0.70% vs. 1.90%; p&#x2009;=&#x2009;0.101) and IS (21.30% vs. 24.50%; p&#x2009;=&#x2009;0.079). Post-PCI angio-IMR was positively correlated with MVO extent (&#x3c1;&#x2009;=&#x2009;0.347; p&#x2009;<&#x2009;0.001) and IS (&#x3c1;&#x2009;=&#x2009;0.324; p&#x2009;<&#x2009;0.001). Receiver operating characteristic analyses showed moderate diagnostic performance of angio-IMR for MVO (area under the curve [AUC] = 0.750; p&#x2009;<&#x2009;0.001), MVO&#x2009;>&#x2009;2.6% (AUC&#x2009;=&#x2009;0.735; p&#x2009;<&#x2009;0.001) and IS&#x2009;>&#x2009;25% (AUC&#x2009;=&#x2009;0.712; p&#x2009;<&#x2009;0.001). The exploratory optimal cut-off values for these endpoints were approximately 40&#x2009;U. CONCLUSIONS: In STEMI patients, a single bolus of r-SAK before PCI was associated with numeric reductions in post-PCI angio-IMR, MVO, MVO extent and IS. Additionally, angio-IMR exhibited a significantly positive correlation with both MVO extent and IS, demonstrating the diagnostic value of this wire-free method for assessing microvascular injury.

Humans

Tracking microplastic contamination across seasons in a freshwater reservoir: Evidence from surface water, sediments, and fishes.

Microplastics (MPs) are prevalent contaminants in aquatic environments, posing substantial ecological and health risks. These particles migrate within the different layers of aquatic bodies with time and affect the respective biota. Thus, to get an in-depth understanding of the particles, this current study investigated the seasonal distribution, morphological and chemical characteristics, along with potential ecological and human health impacts in the samples including surface water, sediment, and fish from a drinking water supplying reservoir in eastern India. Across three different seasons, pre-monsoon, monsoon, and post-monsoon samples were collected using optimized methods. Results revealed distinct seasonal trends: MP abundance in surface water peaked during the monsoon (mean: 1.15 MPs/L), while sediment showed the highest concentrations in the pre-monsoon (mean: 596 MPs/kg), indicating temporal accumulation dynamics influenced by runoff, hydrodynamics, and sedimentation. Fish gut analysis confirmed ingestion of MPs across five species, with concentrations ranging from 26 to 100 MPs/kg, depending on feeding habits. The most dominant MP type were fragments, followed by fibers, films, and beads. Polymer analysis via &#xb5;FTIR identified polyethylene, polypropylene, and polyvinyl chloride as prevalent, with hazard assessments (i.e., Polymer Hazard Index (PHI)) indicating medium to very high ecological risks. Heavy metal association was more dominant in the MPs isolated from sediments than the waterborne MPs. Pollution Load Index (PLI) values were > 1 in most seasons, confirming contamination. Health risk analysis suggested potential exposure through both drinking water and fish consumption. This study emphasizes the need for seasonal monitoring, improved waste management, and mitigation strategies to address MP pollution in freshwater ecosystems.

Microplastics

The impact of body mass index classification on operative characteristics and perioperative outcomes in lumbar microdiscectomy.

INTRODUCTION: Body mass index (BMI) stratification helps classify obesity severity. In patients undergoing microdiscectomy for symptomatic lumbar disc herniation, the effect of obesity on perioperative risk remains incompletely understood. This retrospective single-institution study evaluated whether BMI class influences perioperative risk in a large surgical cohort. METHODS: Adults older than 18&#xa0;years who underwent primary, elective single-level lumbar microdiscectomy between June 2018 and March 2025 with at least 3&#xa0;months of follow-up were included. Patients were grouped by BMI: without obesity (WO, BMI&#xa0;<&#xa0;30), class I (CI, 30-34.9), class II (CII, 35-39.9), and class III (CIII, &#x2265;40). Outcomes were analyzed separately for open microdiscectomy (OM), tubular microdiscectomy (TM), and endoscopic discectomy (ED). Continuous variables were compared using Kruskal-Wallis testing with Dunn post hoc analysis; categorical variables were compared with chi-square tests. Significance was set at p&#xa0;<&#xa0;0.05. RESULTS: A total of 757 patients were included (OM 422, TM 190, ED 145). Higher obesity classes underwent ED more frequently (p&#xa0;=&#xa0;0.038). In the OM cohort (WO 258, CI 97, CII 50, CIII 17), CI had a higher proportion of males and CII a lower proportion (p&#xa0;=&#xa0;0.007). Operative time, length of stay, and estimated blood loss were greatest in CII and CIII patients (all p&#xa0;<&#xa0;0.001). CII patients also had more emergency department visits within 1&#xa0;year than other classes (p&#xa0;=&#xa0;0.026). No differences were found in age, smoking status, disc herniation type, dural tears, intraoperative or postoperative complications, or revision presence/time. In the TM cohort (WO 117, CI 47, CII 21, CIII 5), WO patients were oldest and CIII youngest (p&#xa0;<&#xa0;0.001), with no other significant differences. In the ED cohort (WO 79, CI 31, CII 20, CIII 15), WO patients were oldest and CIII youngest (p&#xa0;=&#xa0;0.004). CIII patients had higher estimated blood loss (p&#xa0;=&#xa0;0.028) and shorter time to revision (p&#xa0;<&#xa0;0.001), while other variables were similar. CONCLUSIONS: ED was used more often in higher obesity classes. In OM, CII and CIII obesity were associated with longer operative time, longer hospital stay, and greater blood loss, likely due to increased exposure requirements. TM and ED showed few obesity-related differences in complications, suggesting minimally invasive approaches may mitigate obesity-related perioperative risk. However, the retrospective design and small number of CIII patients warrant further study.

Humans

Predictors of Efficacy Maintenance After Vunakizumab Discontinuation in Patients With Moderate-to-Severe Plaque Psoriasis: A Post Hoc Analysis of a Randomized Controlled Trial.

BACKGROUND: Efficacy cannot be maintained in some psoriasis patients after biological discontinuation. This study aimed to explore predictors of efficacy maintenance after vunakizumab discontinuation in patients with moderate-to-severe plaque psoriasis. METHODS: This post hoc analysis used data from a phase III trial (NCT04839016); 291 patients with moderate-to-severe plaque psoriasis who achieved 100% improvement in Psoriasis Area and Severity Index (PASI) score at Week 52 were enrolled. Efficacy maintenance was defined as patients who maintained PASI 90 or PASI 100 after 20&#x2009;weeks of vunakizumab discontinuation. RESULTS: There were 44.7% and 72.5% of patients with PASI 100 and PASI 90 maintenance, respectively. In the multivariate logistic regression model, body mass index (BMI) (odds ratio [OR]&#x2009;=&#x2009;0.922, p&#x2009;=&#x2009;0.024) and treatment interruption (OR&#x2009;=&#x2009;0.550, p&#x2009;=&#x2009;0.020) were independently associated with a lower possibility of PASI 100 maintenance; however, the association of family history of psoriasis and the first time of PASI 100 achievement with PASI 100 maintenance did not achieve statistical significance. Duration of psoriasis (OR&#x2009;=&#x2009;0.972, p&#x2009;=&#x2009;0.049) and treatment interruption (OR&#x2009;=&#x2009;0.257, p&#x2009;<&#x2009;0.001) were independently associated with a lower possibility of PASI 90 maintenance. Two nomograms for predicting PASI 90 and PASI 100 maintenance were constructed based on the multivariate models, which disclosed good calibration performance. CONCLUSIONS: PASI 90 and PASI 100 maintenance rates are 72.5% and 44.7% after 20&#x2009;weeks of vunakizumab discontinuation in patients with moderate-to-severe plaque psoriasis. BMI, treatment interruption, and duration of psoriasis predict a lower possibility of efficacy maintenance after vunakizumab discontinuation.

Humans

Psychometric Evaluation of the Breast Inflammatory Symptom Severity Index Versions 2 and 3 Among Lactating Women.

OBJECTIVE: To evaluate the psychometric properties of Versions 2 and 3 of the Breast Inflammatory Symptom Severity Index (BISSI). DESIGN: Secondary data analysis of clinical trial data. SETTING: Private physiotherapy practices, a public tertiary hospital, and a community in Melbourne, Australia. PARTICIPANTS: Women more than 7 days after birth with inflammatory conditions of the lactating breast (N = 43). METHODS: We performed confirmatory factor analysis of the BISSI Version 2 to examine item loading, which informed development of the BISSI Version 3 (V3). We assessed convergent validity by comparing total BISSI V3 scores with human milk sodium to potassium ratio (Na+:K+) at Trial Days 1, 3, and 10 using Bland-Altman plots. We compared item-level scores for size of affected area with objective receiver operating characteristic curve analysis to assess discriminant validity for symptom severity and Cronbach's alpha for internal reliability. RESULTS: After confirmatory factor analysis, we removed two items, resulting in a six-item BISSI V3. All retained items demonstrated comparable loading on the overall scale. Limits of agreement for total BISSI V3 scores and item-level scores for size of affected area were acceptable at all time points, with more than 90% of observations falling within 2 standard deviations of the mean difference, supporting convergent validity. Discriminant validity of the BISSI V3 was supported. We found high internal reliability at both time points CONCLUSION: Our findings provide evidence for the validity and reliability of the BISSI V3 and support its continued development and for clinical use of the BISSI V3 and human milk Na+:K+ analysis to enhance management of inflammatory conditions of the lactating breast.

breastfeeding

Safety, tolerability, and efficacy of RIPK1 inhibitor, SAR443820, in amyotrophic lateral sclerosis (HIMALAYA): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: RIPK1, a protein regulating inflammatory signalling and cell death, is implicated in amyotrophic lateral sclerosis (ALS) pathophysiology. SAR443820 is a selective, oral, CNS-penetrant, reversible RIPK1 inhibitor. We aimed to evaluate the safety, tolerability, and efficacy of SAR443820 in participants with ALS. METHODS: This multicentre, randomised, double-blind, placebo-controlled, phase 2 trial was conducted at 63 clinical sites in 13 countries (Belgium, Canada, China, France, Germany, Italy, Japan, the Netherlands, Poland, Spain, Sweden, the UK, and the USA). Adults (aged 18-80 years) with a diagnosis of possible ALS, clinically probable ALS, clinically probable laboratory-supported ALS, or clinically definite ALS, in accordance with the revised El Escorial World Federation of Neurology criteria, were randomly assigned (2:1) by use of a stratified block design (blocks of three) to receive either 20 mg SAR443820 orally twice per day or matching placebo in the 24-week double-blind period. Randomisation was done centrally using interactive response technology and stratified by geographical region of trial site, region of ALS onset, use of riluzole, use of edaravone, and use of the combination of sodium phenylbutyrate and taurursodiol. Participants, care providers, investigators, and outcomes assessors were masked to trial intervention. The primary outcome was a change in ALS Functional Rating Scale Revised (ALSFRS-R) total score from baseline to week 24 and was calculated for all participants who had an ALSFRS-R total score available at baseline and at week 24. Safety analyses included all randomly assigned participants receiving one dose or more of trial intervention. This trial is registered with ClinicalTrials.gov (NCT05237284) and was terminated early. FINDINGS: Between April 13, 2022, and July 17, 2023, 397 participants were screened and 305 randomly assigned to SAR443820 (n=203) or placebo (n=102); six were excluded from the primary analysis due to missing baseline ALSFRS-R values. Mean age was 56&#xb7;9 years (SD 11&#xb7;5); 183 (60%) participants were male and 122 (40%) were female. Least squares mean change in ALSFRS-R from baseline to week 24 was -6&#xb7;73 (95% CI -7&#xb7;48 to -5&#xb7;98) for SAR443820 group (n=169) and -6&#xb7;32 (-7&#xb7;36 to -5&#xb7;27) for placebo group (n=87). There was no statistically significant difference between the study groups (least squares mean difference -0&#xb7;41 [95% CI -1&#xb7;71 to 0&#xb7;88]). Participants in the SAR443820 group had higher incidence of adverse events (171 [85%] of 202 vs placebo 80 [78%] of 102) and treatment discontinuations (28 [14%] of 202 vs placebo five [5%] of 102), with elevated hepatic enzymes being the most common cause. Nine deaths occurred in the double-blind period (seven [3%] of 202 in the SAR443820 group and two [2%] of 102 in the placebo group); none was attributed to SAR443820. INTERPRETATION: SAR443820 did not show clinical benefit and was associated with higher hepatic enzyme increase, indicating that further clinical development of SAR443820 in ALS is not warranted. FUNDING: Sanofi.

Humans

The Effect of Pulsed Electromagnetic Field on Pain and Foot Function Index in Patients With Plantar Fasciitis.

The plantar fascia is a thick band of connective tissue that originates from the heel, and its inflammation is the most common cause of heel pain in adults. The Pulsed Electromagnetic Field (PEMF) is a non-invasive modality in the field of physiotherapy. This study aimed to determine the effects of PEMF on pain scores and the Foot Function Index (FFI) in patients with plantar fasciitis (PF). In this clinical trial study, 40 patients with PF, aged between 20 and 68 years, were randomly assigned in a block design into two groups: the Conventional Physiotherapy (CP) group and the CP plus PEMF (CPP) group. The Numerical Pain Rating Scale (NPRS) and the FFI questionnaire were used to assess the pain score (morning and evening pain) and foot function, respectively. Assessments were conducted before the study, at the tenth session of the CP and CPP groups, and 4 weeks later. The study variables in both the CP and CPP groups changed significantly (p&#x2009;<&#x2009;0.05). In comparing the results between the two groups, the reduction in evening pain scores in the CPP group was significant compared to the CP group (p&#x2009;<&#x2009;0.05). In comparison, there was no significant difference in morning pain scores between the two groups. The FFI score in the CPP group significantly decreased compared to the CP group. Both CP and CPP are effective in reducing pain and the FFI in patients with PF. The addition of PEMF to CP demonstrates a more significant effect on reducing evening pain and somewhat on reducing the FFI in patients compared to CP alone. However, it did not have an additional effect on reducing morning pain. Bioelectromagnetics. 00:00-00, 2026. &#xa9; 2026 Bioelectromagnetics Society.

Humans