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PubMed2026

Effects of transcutaneous electrical acupoint stimulation versus acupressure on the trajectories of multidimensional adverse reactions to chemotherapy in breast cancer patients: a secondary analysis of a randomized controlled trial.

BACKGROUND: Chemotherapy for breast cancer often induces multidimensional adverse reactions such as nausea and vomiting, anxiety, depression, and sleep disturbances. These symptoms are interrelated and may evolve dynamically, impacting patients' treatment outcomes and quality of life. As non-pharmacological interventions, transcutaneous electrical acupoint stimulation (TEAS) and self-acupressure (SA) have shown potential in alleviating symptoms. However, their long-term effects on the joint developmental trajectories of these multidimensional symptoms (nausea and vomiting, anxiety, depression, and sleep disturbances) remain unclear. OBJECTIVE: This study aimed to identify potential trajectory class of multidimensional adverse reactions in breast cancer patients undergoing chemotherapy and to explore the differential effects of TEAS and SA on different trajectory subgroups. METHODS: This was a secondary analysis of a randomized controlled trial. A total of 189 breast cancer patients receiving chemotherapy were included. The Group-Based Multi-Trajectory Model (GBMTM) was employed to identify joint developmental trajectories of acute/delayed chemotherapy-induced nausea and vomiting (CINV), anxiety, depression, and sleep quality during chemotherapy. Subsequently, causal forest was used to analyze the average treatment effects (ATE) of TEAS (vs. control group) and SA (vs. control group) on patients' symptom trajectory. RESULTS: Multidimensional adverse reactions were classified into two heterogeneous trajectories: a "High Symptom Burden-Persistent (HSBP)" type (n = 101) and a "Low Symptom Burden-Relieving (LSBR)" type (n = 88). The persistent high incidence of acute CINV contrasted sharply with the comprehensive relief of other symptoms in the latter group. Causal forest suggested that both TEAS and SA significantly increased the probability of patients being classified into the "LSBR" trajectory. The ATE was 0.147 (95% CI: 0.143, 0.151) for TEAS, slightly lower (P < 0.05) than 0.176 (95% CI: 0.162, 0.190) for SA.  CONCLUSION: Multidimensional adverse reactions in breast cancer patients undergoing chemotherapy exhibit heterogeneity in their trajectories. Both TEAS and SA were associated with a higher probability of patients being classified into a more favorable symptom trajectory-LSBR. The multidimensional trajectory identification with treatment effect estimation may serve as a useful analytical strategy for future longitudinal research in cancer chemotherapy-induced adverse reactions symptom management. CLINICAL TRIAL REGISTRATION: ChiCTR2300077667 (Chinese Clinical Trial Registry, https://www.chictr.org.cn/ ), Registered 15 November 2023.

Humans↗

PubMed2026

Patient-reported outcomes in pediatric regional anesthesia trials: current use and limitations.

PURPOSE OF REVIEW: This review examines the current use and limitations of patient-reported outcome measures (PROMs) in pediatric regional anesthesia research. Despite the increasing emphasis on patient-centered outcomes, existing pediatric outcome assessment frameworks may inadequately capture the pain experience and interference with daily living. RECENT FINDINGS: Across 17 identified randomized controlled trials and 15 ongoing studies, PROM use remains highly variable, with consistent reliance on observational pain scales such as the Face, Legs, Activity, Cry, and Consolability scale and limited incorporation of standardized, longitudinal health-related quality-of-life measures. SUMMARY: Current pediatric PROM frameworks remain fragmented, limiting comprehensive evaluation of recovery. Greater standardization and incorporation of developmentally appropriate, longitudinal outcome measures are needed to better align clinical research with meaningful patient-centered endpoints and to improve assessment of functional and psychosocial recovery.

Humans↗

PubMed2026

Early-stage trajectories of social-occupational functioning and long-term functional outcome prediction in early psychosis: A 12-year follow-up of the randomized controlled trial on extended early intervention.

BACKGROUND: Functional impairment in psychosis often persists despite symptomatic remission. There is a paucity of research examining early-course psychosocial functioning trajectories, and none has been conducted to examine relationship between the trajectories and prospective long-term functional outcomes in early psychosis sample. METHODS: We conducted 12-year follow-up of a randomized controlled trial on extended early intervention for first-episode psychosis to identify early-course social-occupational functioning trajectories and their baseline predictors and associations with 12-year outcomes. Participants who completed Social and Occupational Functioning Scale (SOFAS) scores at three or more timepoints between baseline and 3-year follow-up were included in the study. Premorbid adjustment, illness characteristics, symptom severity, functioning, and treatment profiles were assessed. Latent growth mixture modeling was employed to derive early-course social-occupational functioning trajectories based on SOFAS scores over 3-year follow-up. RESULTS: A total of 148 participants were included in this study, with 106 patients having completed the 12-year follow-up. Our results identified four distinct trajectories, including persistently-good class, gradually-improved class, suboptimal-stable class, and persistently-poor class. Patients in persistently-poor class had more severe negative symptoms at baseline compared to patients in persistently-good class. Patients with persistently-poor trajectory had worse long-term outcomes than those with other classes in the majority of functional measures at 12-year follow-up. CONCLUSIONS: The majority of patients were classified in early-stage suboptimal or poor functional trajectories. Above one-fourth of the participants exhibited persistently-poor social-occupational functioning trajectory, which predicted worse functional outcomes at 12-year follow-up. These findings highlighted the importance of tracking functional changes during the initial years of illness.

Humans↗

PubMed2026

A review on the environmental distribution, toxic effects, bioaccumulation characteristics and risk assessment of short-chain chlorinated paraffins.

Chlorinated paraffins (CPs) are synthetic chemicals, widely used as flame retardants and plasticizers. As emerging contaminants, short chain chlorinated paraffins (SCCPs) have attracted tremendous attention due to their persistence, chronic toxicity, long-range transport potential and bioaccumulation potential. This review synthesizes global data on SCCPs' environmental occurrence, toxicological impacts, and bioaccumulation characteristics. SCCPs are ubiquitously detected in various environmental media, including water, sediment, air, soil, and biota. Ecotoxicological studies reveal that SCCPs have lethality, carcinogenicity, growth and developmental toxicities, organs toxicities and endocrine-disrupting effects across species, which pose risks to ecological systems and human health. In addition, the bioaccumulation effects of SCCPs in terrestrial and aquatic ecosystems were analyzed, and proposed the key factors affecting the bioaccumulation of SCCPs. Finally, the risk assessment of SCCPs contamination in the surface water and the soil was carried out, and all soil and most water bodies were found to be low risk. The present study could provide scientific basis and reference for environmental management of CPs products.

Paraffin↗

PubMed2026

To Treat or Not to Treat: Navigating Early-Stage CLL in the Era of Targeted Therapy.

Chronic lymphocytic leukemia (CLL) is most frequently diagnosed at early, asymptomatic stages (Rai 0/Binet A), in which a watch-and-wait strategy remains the standard of care, based on historical trials demonstrating no overall survival benefit from early treatment. Over the past two decades, however, substantial advances in genomic profiling-including immunoglobulin heavy-chain variable region (IGHV) mutational status, TP53 disruption, recurrent gene mutations, and complex karyotype-have uncovered marked biological heterogeneity among early-stage patients and substantially improved prediction of disease progression. In parallel, targeted therapies such as Bruton tyrosine kinase (BTK) inhibitors and venetoclax-based combinations have transformed the management of symptomatic CLL, raising renewed interest in whether early intervention might favorably alter the natural history of biologically high-risk disease. In this review, we critically examine the evolution of prognostication in early-stage CLL, integrate contemporary molecular and clinical risk models, and summarize evidence from both historical chemotherapy-era studies and modern early-intervention trials. We discuss key unresolved controversies, including reliance on surrogate endpoints, the risks of overtreatment, and the persistent absence of an overall survival benefit across all early-treatment strategies. Finally, we outline future research priorities, including refined genomic stratification, minimal residual disease-driven (MRD)-driven approaches, and combination targeted therapies currently under investigation. Despite renewed interest in preemptive treatment, available evidence supports continued observation for asymptomatic patients outside clinical trials.

Humans↗

PubMed2026

Sugar rationing during the first 1000 days and early onset cancer: a natural experiment.

BACKGROUND: The "first 1000 days" of life is a critical window for metabolic programming, while the long-term oncological consequences of nutritional exposures during this period remain understudied. OBJECTIVES: We aimed to evaluate whether restricted sugar intake in utero and during early childhood reduces risk of early onset cancer diagnosis and mortality in adulthood, utilizing a natural experiment. METHODS: We analyzed 63,819 United Kingdom Biobank participants born between October 1951 and March 1956, spanning the end of United Kingdom sugar rationing (September 1953). Leveraging a quasi-experimental birth cohort design, we compared participants exposed to sugar rationing in utero and during infancy with those unexposed. Early onset cancer incidence (≤50 y) and mortality were ascertained via integrated national Cancer Registry and hospital inpatient records. Multivariable Cox proportional hazards models (including Gompertz distribution) were used to estimate hazard ratios (HRs), with exploratory site-specific analyses. RESULTS: Among 63,819 participants (56.3% female), 40,397 were exposed to rationing and 23,422 were unexposed. Early life sugar restriction significantly reduced early onset cancer risk (HR: 0.66; 95% confidence interval: 0.53, 0.81; P < 0.001). A dose-response relationship was observed, with peak protection in individuals exposed for ≤24 mo postnatally. This protection was observed systemically across solid tumors, independent of specific cancer sites. Specificity was corroborated by null associations with negative controls (herpes zoster and cataract). No significant difference was found for cancer-specific mortality. CONCLUSIONS: Restricting sugar intake during the first 1000 days is associated with a reduced risk of early onset cancer, extending the disease-free lifespan. The divergence between reduced incidence and unchanged mortality suggests early life metabolic environments primarily influence tumor latency rather than biological aggressiveness. These findings highlight the potential long-term public health implications of early life dietary guidelines against the rising burden of early onset cancer.

Humans↗

PubMed2026

Infant Dietary Patterns and Early Childhood Weight Outcomes: A Secondary Analysis from the Starting Early Program Trial.

BACKGROUND: The Starting Early Program (StEP) promotes healthy nutrition during early life and leads to healthier child weight, but whether dietary patterns contribute to weight or mediate StEP weight outcomes has not been studied. OBJECTIVES: This secondary analysis identified infant dietary patterns in StEP, determined associations between dietary patterns and child weight outcomes, and examined whether dietary patterns mediated the relationship between StEP and child weight. METHODS: Data were from 377 mother-infant dyads in a randomized trial testing the efficacy of StEP. Dietary patterns at 10 months were identified using latent class analysis. Child weights were abstracted from medical records at 12, 24, and 36 months. Associations between infant dietary patterns and weight-for-age z-score (WFAz) and likelihood of being classified as overweight (WFA ≥85th percentile) were assessed using linear and logistic multivariable regression models. Mediation was used to assess intervention effects on WFAz via impacts on infant dietary patterns. RESULTS: Four classes of infant dietary patterns were identified: Breastfed-High variety, Formula fed-High variety, Formula fed-Low variety, and Mixed fed-Low variety. Compared to the Breastfed-High variety class, infants in the Formula fed-Low variety class had higher WFAz and were more likely to be classified as overweight at 24 and 36 months. Participation in StEP increased membership in Breastfed-High variety, which mediated the association between StEP and lower WFAz at 24 months. CONCLUSIONS: Infant dietary patterns were identified, and some were associated with child overweight. StEP was associated with a dietary pattern most consistent with guidelines, which mediated intervention effects on child weight.

Humans↗

PubMed2026

Neonatal complications in late-preterm and early-term infants: a systematic review of observational studies.

This is a protocol for a Cochrane review (flexible). The objectives are as follows: To assess neonatal complications, specifically neonatal mortality and morbidities, in late-preterm and early-term infants compared to full-term newborns.

Humans↗

PubMed2026

Insights into the regulation of the HOTAIR proximal promoter.

HOTAIR (HOX transcript antisense RNA) is a HOXC-cluster long intervening non-coding RNA (lincRNA) whose cancer relevance is tightly coupled to how its transcription is wired into hormone, hypoxia, inflammatory, and developmental signaling. HOTAIR is known to associate with cancer cell proliferation, motility, tumor invasion, and metastasis. The present mini-review focuses on the regulatory architecture and mechanistic complexity of HOTAIR transcriptional regulation, with emphasis on three organizing principles. First, we consider the impact of promoter choice between a canonical proximal promoter (P1), which supports the 2.2-2.4 kb transcript, and an alternative upstream promoter/TSS (P2), which contributes to context-dependent transcription initiation. Second, we examine the long-distance enhancer-promoter communication between HOTAIR distal enhancer and P1/P2. Third, we summarize the recent epigenetic and epi-transcriptomic mechanisms involved in HOTAIR transcript initiation and elongation. A combination of these events determines isoform-specific transcription to govern cell-type-, context-, and cancer specific modulation of HOTAIR expression that promotes tumor formation and cancer progression. Finally, the review proposes how large-scale RNA datasets, long-read sequencing, and isoform-specific studies can refine our understanding of this versatile lincRNA's regulation.

Humans↗

PubMed2026

Candidate biomarkers for early Giardia duodenalis infection revealed by time-resolved secretome proteomics.

Giardia duodenalis is a zoonotic protozoan parasite that causes giardiasis in humans and other mammals. Early diagnosis remains challenging because current diagnostic methods, including microscopy and enzyme-linked immunosorbent assays (ELISAs), primarily detect established infections. Consequently, a critical diagnostic gap exists during the early stage of infection within the first 2-48 h following exposure. To address this limitation, we characterized the proteins released by in vitro-cultured G. duodenalis trophozoites under serum-free conditions and evaluated their potential as early diagnostic biomarkers. Proteomic analysis of culture supernatants collected during early trophozoite incubation identified 31,773 peptides corresponding to 2504 quantifiable proteins. Temporal profiling showed distinct secretion patterns, including proteins that peaked during the early stage, progressively accumulated over time, or remained persistently abundant throughout the incubation period. Based on their secretion characteristics and predicted immunogenic properties, five candidate biomarkers were selected for further evaluation. Polyclonal antibodies raised against selected candidates successfully detected the corresponding proteins in serum-free culture supernatants, providing preliminary evidence for their potential utility as early-stage diagnostic targets. These findings identify stage-associated candidate proteins that may serve as a resource for future early giardiasis diagnostic development, provide a valuable resource for investigating host-parasite interactions, and establish a foundation for future diagnostic assay development. However, further validation in clinical and biological samples is required to confirm their diagnostic applicability. SIGNIFICANCE: Giardiasis, caused by Giardia duodenalis, is a major diarrheal disease worldwide. Although enzyme-linked immunosorbent assays (ELISAs) provide rapid detection, their diagnostic utility is limited by the lack of biomarkers capable of identifying infection during its earliest stages, creating a critical gap in the detection of active infection within 2-48 h following exposure. Using data-independent acquisition proteomics, this study provides a time-resolved characterization of proteins released by G. duodenalis trophozoites into serum-free culture supernatants. Our findings reveal temporal secretion dynamics of protein secretion and identify candidate biomarkers with potential utility for the development of early-stage diagnostic assays pending rigorous biological and clinical validation. In addition, this proteomic resource provides a foundation for investigating host-parasite interactions and may facilitate the development of future point-of-care diagnostic strategies.

Giardiasis↗

PubMed2026

Early mobilization within 24 to 48 h improves postoperative clinical outcomes in older adults with hip fracture: A systematic review and meta-analysis.

BACKGROUND: Hip fracture is a major public health concern among older adults, often resulting in prolonged disability, institutionalization, and increased healthcare burden. Early mobilization has been widely recommended to enhance postoperative recovery; however, there is a lack of consolidated evidence quantifying its impact on clinical and functional outcomes. This study aimed to synthesize and evaluate the impact of early mobilization following hip fracture surgery in older adults and to explore potential sources of heterogeneity to better inform clinical and nursing practice. METHODS: A comprehensive literature search was conducted across seven databases (PubMed, Embase, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, and Emcare) from inception to June 15, 2025. Eligible studies included randomized controlled trials and observational cohort studies comparing early mobilization (defined as ambulation within 24 to 48 h postoperatively) to delayed or usual mobilization in patients undergoing hip fracture surgery. Primary outcomes included mortality, discharge destination, and length of hospital stay. Secondary outcomes included postoperative complications, functional recovery, and readmission. Risk of bias was assessed using funnel plots and Egger's test. RESULTS: Twenty-six studies involving 297,435 patients were included. Compared with delayed mobilization, early mobilization significantly reduced 30-day mortality (relative risk = 0.40, 95% confidence interval: 0.25-0.64) and 1-year mortality (relative risk = 0.57, 95% confidence interval: 0.40-0.80) (both p < 0.05). In regional analyses of pooled mortality, similar reductions were observed across Asia-Pacific, North America, and Europe. Patients receiving early mobilization were more likely to be discharged home and had shorter hospital stays. Early mobilization also resulted in a reduced risk of postoperative complications (relative risk = 0.79, 95% confidence interval: 0.74-0.84, p < 0.05), with specific improvements in pneumonia and thromboembolism rates. Functional independence was significantly improved, as shown by higher Barthel Index scores and increased odds of achieving Functional Independence Measure ≥5 at discharge. No significant difference was observed in readmission rates. CONCLUSIONS: lization within 24 to 48 h following hip fracture surgery was associated with favorable outcomes, including reduced mortality, improved functional independence, higher rates of discharge to home, shorter hospital length of stay, and fewer postoperative complications. Although heterogeneity across studies and the predominance of observational evidence warrant cautious interpretation, these findings support current recommendations for early mobilization and highight the potential value of structured and standardized mobilization protocols in routine postoperative hip fracture care.

Humans↗

PubMed2026

Analysis of the Relationship between Early Clinical Factors and Glasgow Outcome Scale in Patients With Traumatic Brain Injury.

OBJECTIVE: This study aimed to evaluate the association between early clinical factors and the Glasgow outcome scale (GOS) in patients with traumatic brain injury (TBI). METHODS: We conducted a retrospective analysis of 98 TBI patients who underwent emergency surgery between January 2021 and January 2024. Based on GOS scores at 6 months post-surgery, patients were classified into a favorable outcome group (GOS ≥ 4, defined as moderate disability or good recovery, n = 58) and an unfavorable outcome group (GOS < 4, i.e., death, persistent vegetative state, or severe disability, n = 40). Baseline and early clinical parameters were compared between groups. Statistically significant variables from univariate analysis were entered into a multivariate logistic regression model to identify independent prognostic factors. RESULTS: Significant intergroup differences were observed in age, time from injury to surgery, bleeding site, midline shift, Glasgow coma scale (GCS) score at admission, blood glucose level, and D-dimer level (all p < 0.05). Multivariate analysis confirmed that age, time from injury to surgery, GCS score, blood glucose, and D-dimer level were independent predictors of GOS (all p < 0.05). CONCLUSION: Early clinical factors, including age, time to surgery, GCS score, blood glucose, and D-dimer level, independently influence GOS in TBI patients. Time from injury to surgery emerged as a potentially modifiable factor in this cohort, suggesting that minimizing delays may improve outcomes.

Humans↗

PubMed2026

Long-term motor outcomes after parent-administered early physiotherapy in children born very preterm.

OBJECTIVE: This observational follow-up study investigated whether early parent-administered physiotherapy during the neonatal period was associated with motor outcomes in childhood, and compared these outcomes between two preterm groups and a term-born control group. STUDY DESIGN: This is a follow-up of a pragmatic randomised controlled trial that initially included 153 infants born very preterm (≤32 weeks' gestation), randomised to either early parent-administered physiotherapy or standard care, between 34 and 37 weeks' gestation. At 7-10 years, motor outcomes were assessed in 92 children (intervention, n = 43; standard care, n = 49) and in 83 term-born controls. The primary outcome was the Movement Assessment Battery for Children-Second Edition (MABC-2). Group differences were analysed using linear mixed models adjusted for age, sex, and parental education. Odds ratios (ORs) were calculated for scores ≤5th and ≤ 15th percentiles to estimate the likelihood of having or being at risk for movement difficulties. RESULTS: Mean MABC-2 total score was 9.0 (SD3.0) in the intervention group, 9.6 (SD3.0) in the standard care group, and 10.8 (SD2.9) in the control group. Adjusted mean difference between the intervention and the standard care groups did not differ but both the intervention and standard care groups had lower scores than the control group (-1.2; 95% CI: -2.3 to -0.2 and -0.6; 95% CI: -1.6 to 0.3, respectively). Adjusted ORs for scoring ≤5th or ≤15th percentile did not differ in either preterm group compared with the control group. CONCLUSION: At 7-10 years, motor outcomes did not differ between children born very preterm who received three-week parent-administered physiotherapy and those who received standard care during the neonatal period. However, both preterm groups had lower motor scores than term-born peers.

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PubMed2026

Innovation-related perception as a key driver of alternative protein acceptance: evidence from an early-stage model for cultivated meat and algae-/microalgae-based alternative protein products in Italy.

Alternative proteins are increasingly considered part of the transition toward more sustainable food systems, yet their diffusion depends critically on consumer acceptance. This study investigates the early-stage acceptance of two alternative protein categories in Italy-cultivated meat and algae-/microalgae-based alternative protein products. Focusing on the first three phases of acceptance, the analysis examines how innovation-related perception (IRP) shapes consumer perceived value (CPV), consumer perceived risk (CPR), and subsequent affective (AFF), cognitive (COG), and conative (CON) responses. Data were collected through an online survey administered to 238 Italian respondents and analysed using partial least squares structural equation modelling (PLS-SEM). The results show that IRP is the main upstream driver of early-stage acceptance in both product domains: more favourable perceptions strongly increase perceived value and reduce perceived risk. In turn, CPV exerts a much stronger influence than CPR on both affective and cognitive attitudes. A tentative cross-model comparison suggests only a descriptive variation in the final transition toward conative acceptance: affective and cognitive responses were both significant in the two models, with a relatively larger affective coefficient for cultivated meat and more balanced coefficients for algae-/microalgae-based products. Overall, the findings support a process-based interpretation of alternative protein acceptance and highlight the central role of innovation-related perception in shaping early consumer responses. These results provide relevant implications for communication strategies, product positioning, and policy actions aimed at improving the acceptability of alternative proteins in food cultures characterised by strong culinary traditions.

Italy↗

PubMed2026

Deimplementation of inappropriate feeding practices in early care and education: a Hybrid Type 3 cluster-randomized trial.

BACKGROUND: The science of deimplementation-reducing harmful or ineffective practices-has focused almost exclusively on clinical prescribing, with no studies conducted in community or educational settings. Early care and education (ECE) settings offer a strategic venue for shaping eating behaviors, with children consuming up to 500 meals annually in these environments. However, ECE educators routinely use feeding practices that undermine self-regulation, including pressuring children to eat, rushing mealtimes, and offering food as reward. These practices contribute to food aversions, diminished self-regulation, and obesity risk. METHODS: We will conduct a Hybrid Type 3 cluster-randomized trial evaluating a co-designed deimplementation strategy package (WISE Words) across 88 ECE sites in Arkansas and Louisiana. Sites will be randomized 1:1 to WISE Words or usual practice, with usual practice sites receiving the intervention after two years (waitlist design). WISE Words includes six strategies: dynamic training using improvisation methods, peer learning collaboratives with goal setting, external facilitation, audit and feedback, environmental reminders, and tailored educational materials. The primary outcome is de-adoption of inappropriate feeding practices measured via direct mealtime observation (Table Talk). Secondary outcomes include adoption of evidence-based practices, acceptability, appropriateness, and sustainability at 12- and 24-months post-intervention. Child outcomes include Body Mass Index, skin carotenoid levels (Veggie Meter) willingness to try new foods (observed) and food neophobia (teacher and caregiver report). An explanatory sequential mixed methods design will test mechanisms of change derived from the Implementation Trust Building Theory of Change examining whether trust mediates strategy effects on outcomes. DISCUSSION: This trial extends deimplementation science into community settings by targeting culturally embedded behavioral practices rather than clinical prescribing behaviors. Results will inform approaches to shifting entrenched practices in ECE and similar settings while testing trust as a deimplementation mechanism. Sustainability assessments will address a notable gap, as few studies have examined whether deimplementation effects persist. TRIAL REGISTRATION: NCT07101321, July 20, 2025.

Humans↗

PubMed2026

Estrone disrupts early reproductive development in juvenile male Siniperca chuatsi and is associated with brain and gonadal responses.

Whether estrone (E1)-associated disruption of early reproductive development in fish is accompanied by brain responses in addition to direct gonadal effects remains unclear. Here, juvenile Siniperca chuatsi, a non-model but economically important freshwater species, were exposed for 60 d to 0, 0.01, 0.1, and 1.0 μg/L E1, spanning environmentally reported and elevated concentrations. By integrating waterborne concentration monitoring, histopathology, transcriptomics, and quantitative real-time PCR (qPCR) validation, we evaluated E1-associated changes in brain and gonadal tissues during early reproductive development. Waterborne E1 concentrations remained generally stable throughout the exposure period. At the highest tested concentration (1.0 μg/L), E1 caused neuronal vacuolation and pyknosis in the hypothalamic region and induced distinct ovarian-like structures in the gonads of genetic males. In the brain, cyp19a1, crhr1, and adcy2a were significantly upregulated, whereas egr1 was significantly downregulated, indicating transcriptional changes in genes associated with local estrogen conversion, stress-response/cAMP signaling, and neuronal activity-related regulation within a broader injury/stress-response background. In the gonad, RNA-seq analysis showed significant downregulation of star2, hsd3b1, cyp17a1, and cyp11b and significant upregulation of hsd17b1, suggesting alterations in steroidogenesis-related gene expression at the transcriptomic level. qPCR analysis of selected gonadal candidate genes showed expression directions generally consistent with the RNA-seq results, and these molecular patterns were consistent with the feminized histological phenotype. Together, these results indicate that E1 can disrupt early reproductive development in juvenile S. chuatsi and support a cautious working model in which E1 exposure is accompanied by concurrent brain and gonadal responses. This study provides new evidence for understanding the toxic effects and ecological risk implications of natural estrogen E1 during early fish development.

Animals↗

PubMed2026

Effect of cognitive enhancement therapy for early course schizophrenia on gray matter volume: A confirmatory multisite randomized clinical trial.

BACKGROUND: Cognitive Enhancement Therapy (CET) is an evidence-based cognitive remediation intervention for early course schizophrenia with established benefits for cognition. CET may protect against broad temporolimbic gray matter volume loss associated with cognitive improvement, but this finding has yet to be replicated. This research reexamined if CET protects against temporolimbic gray matter volume loss in an independent and larger multisite early course sample, and if this neuroprotective effect predicts cognitive and social adjustment improvement. METHODS: Ninety-nine participants with early course schizophrenia completed MRI, cognitive, and social adjustment assessments at baseline, 9 (mid-treatment), and 18 (end of treatment) months. Linear mixed-effects models examined the differential impact of CET (n = 56) compared to Enriched Supportive Therapy (n = 43) on temporolimbic gray matter volume in regions-of-interest (ROIs) that previously demonstrated CET-related neuroprotection (primary ROIs), as well as frontotemporal ROIs outlined in the first trial (secondary ROIs). RESULTS: The right rostral anterior cingulate was the only primary ROI to demonstrate a significant group × time interaction, but was unrelated to cognitive and social adjustment change. No secondary ROIs exhibited a differential treatment effect. CONCLUSION: This confirmatory trial did not recapitulate the observed broad pattern of CET-related temporolimbic gray matter volume neuroprotection. Consistent with the larger literature demonstrating limited evidence of cognitive remediation effects on the brain in schizophrenia, these findings underscore the need for continued investigation of CET-related changes with other neuroimaging modalities, especially given its established cognitive benefits. Such information is critical for cognitive remediation optimization based on validated therapeutic mechanisms.

Humans↗

PubMed2026

L-glutamine supplementation improves porcine sperm quality and early embryo development during in vitro fertilization.

L-glutamine (Gln), as a key additive in porcine sperm capacitation medium and in vitro fertilization (IVF) systems, has been shown to significantly improve sperm motility and survival rates. However, its precise roles during porcine IVF and subsequent early embryonic development remain elusive. This study utilized an IVF model in pigs to investigate the effects of glutamine on sperm quality and embryonic development. We found that Gln supplementation during sperm treatment significantly improved sperm quality, as evidenced by reduced reactive oxygen species (ROS) production and early apoptosis, while enhancing calcium ion levels and endoplasmic reticulum activity. Supplementing glutamine during embryo culture reduced polyspermy rates, promoted zygotic genome activation (ZGA) and accumulation of 5-ethynyluridine (EU) and histone modifications (H3K4me3 and H3K27ac) at the two-cell and four-cell stages, increased blastocyst formation rates and total cell numbers, while simultaneously reducing DNA damage and early apoptosis during the blastocyst stage. In summary, these findings demonstrate that Gln enhances porcine IVF outcomes by improving sperm quality, reducing polyspermy, and facilitating early embryonic development, thereby providing a basis for optimizing culture systems.

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