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GATA2 deficiency: enhancer deregulation, immune surveillance failure, and clonal evolution.

Germline mutations in GATA2 cause a syndromic inborn error of immunity characterized by cytopenia, infections, immune dysregulation, and a marked predisposition to myelodysplastic syndrome and acute myeloid leukemia. Initially defined by the DCML phenotype-dendritic cell, monocyte, B- and NK-cell deficiency-GATA2 deficiency is now recognized as a disorder of global immune-hematopoietic homeostasis. Recent multi-omics and experimental models reveal enhancer-driven inflammatory rewiring, IRF8-dependent lineage imbalance, and premature hematopoietic aging. In parallel, adaptive immune defects, including impaired B- and T-cell development and function, contribute to defective immune surveillance. These alterations not only explain susceptibility to infection but also shape clonal evolution and malignant transformation. Clinically, improved risk stratification and transplant outcomes underscore the importance of early recognition and monitoring of immune dysfunction. GATA2 deficiency thus represents a paradigm linking immune dysregulation, inflammatory stress, and cancer predisposition.

Humans

Latent profile analysis of pregnant exercise adherence and the relationship with demographic and socio-psychological factors: a multicentre cross-sectional study.

BACKGROUND: Pregnancy physical activity (PA) and exercise benefits both mothers and babies, but requires sustained adherence. Many pregnant women fail to meet recommended levels. The reasons for low adherence comprised fluctuating physiological and environmental factors. This study aims to identify discrete profiles of pregnant women based on exercise adherence and to examine differences in demographic and socio-psychological factors across these profiles. METHODS: A survey was conducted among 1,255 pregnant women in three hospitals in Shenzhen, Dongguan, and Shunde, China, using the Exercise Adherence Rating Scale (EARS), the Pregnancy Exercise Self-Efficacy Scale (P-ESES), and the Pregnancy Physical Activity Social Support Scale (P-PASSS). In the analysis, EARS items were scored higher, indicating a healthier state (e.g., sufficient time and energy). Latent profile analysis (LPA) was employed to classify adherence profiles, and multinomial logistic regression was used to examine differences in demographic, self-efficacy, and social support across four groups. RESULTS: Four profiles of exercise adherence were identified: (1) Profile 1 (16.97%), characterized by deficits in time and energy, (2) Profile 2 (15.22%), a group with sufficient time resources but the lowest self-efficacy, (3) Profile 3 (43.98%), characterized by high adherence despite moderate barriers, and (4) Profile 4 (23.83%), a group with optimal exercise adherence, confidence, and resources. Women with higher P-ESES (OR: 1.14-1.38) and P-PASSS (OR: 1.04-1.06) scores were more likely to be in Profiles 3 and 4. Additionally, women's partners who never or occasionally exercise were significantly more likely to be categorized into Profile 1 (OR = 0.18 for Profile 4 vs. Profile 1). Furthermore, the first trimester emerged as a significant risk period for lower exercise adherence, whereas overweight/obesity was independently associated with higher odds of membership in Profile 4. CONCLUSION: The study identified four distinct profiles of exercise adherence among pregnant women. 32.19% of participants were in the two lower exercise-adherence groups. Pregnant women in Profile 1 were characterized by challenges related to a lack of time and knowledge. Participants in Profile 2 showed the lowest exercise self-efficacy and social support among the four profiles. Furthermore, women in early pregnancy were more likely to have lower adherence profiles. Hence, targeted interventions addressing these specific groups are warranted to improve exercise adherence during pregnancy.

Humans

Influence of ovarian maturity, age, and mating status on the antennal responses of wild and laboratory reared Xyleborus affinis (Coleoptera: Curculionidae: Scolytinae) to ethanol.

Xyleborus affinis Eichthoff is a neotropical ambrosia beetle that, in certain regions such as the United States and Mexico, has been associated with exotic phytopathogenic fungi causing extensive tree mortality. Although studies relating its olfactory response to volatile compounds and trapping systems have been published, factors such as the insect's physiological condition, which can affect its recognition or response to odors, have not been studied. Here, we evaluated the electroantennographic (EAG) response of wild and laboratory reared X. affinis females to 70% ethanol, a compound known to attract these insects. The experimental design was developed to consider and compare the following conditions: (i) females collected inside and outside host-galleries, (ii) sexual maturity (with mature and immature ovaries), (iii) age (0, 1, 3, and 5 d after emergence), and (iv) mating status (virgins and mated). Our results indicate that most of the wild females located outside the galleries were sexually mature but exhibited significantly lower EAG response than those inside the galleries. Regarding mating status, mated females exhibited significantly stronger antennal responses compared to virgins, whereas age did not affect antennal sensitivity. Finally, we provide images of the hitherto undescribed reproductive system of X. affinis females, a key element that enabled this investigation. The information generated offers a useful foundation for future studies aimed at understanding the physiological mechanisms and other critical factors related to sensory perception and reproductive condition. For example, factors that may influence the behavior and attraction of X. affinis females to host semiochemicals.

Animals

Advances in cereal protein applications for infant and Young child nutrition.

BACKGROUND: The increasing use of plant-derived proteins in infant and young child nutrition necessitates tailored amino acid profiles, high digestibility and strict safety controls. Cereal proteins, such as rice, oat, maize, millet, barley, and wheat, are widely used in complementary foods but face intrinsic limitations, notably lysine and tryptophan deficits, antinutritional factors that reduce bioavailability, gluten immunogenicity in wheat/barley, and inorganic arsenic risks in rice. SCOPE AND APPROACH: This review synthesizes recent advances in processing and formulation strategies, including enzymatic hydrolysis, fermentation, germination, extrusion, cereal-legume complementation, and micronutrient fortification. Their impacts on digestibility, techno-functionality, iron and zinc bioavailability, and protein quality, including Protein Digestibility-Corrected Amino Acid Score (PDCAAS) and Digestible Indispensable Amino Acid Score (DIAAS) are critically reviewed using data from in vitro assays, product development, and clinical trials. KEY FINDINGS AND CONCLUSIONS: Processing and blending approaches can substantially improve protein digestibility, amino acid balance and micronutrient availability, and hydrolyzed rice protein holds clinical promise for cow's milk protein allergy (CMPA). However, most evidence is preclinical, reporting of protein quality is inconsistent, and industrial translation is constrained by sensory, shelf-life, contaminant and cost issues. We recommend standardized DIAAS-based reporting, large-scale feeding trials, sensory /stability optimization, and targeted exploration of underutilized grains (e.g., oat, millet) with active allergen monitoring. Prioritizing amino acid-focused formulation coupled with strategies to enhance micronutrient bioavailability will accelerate safe adoption of cereal proteins in early-life nutrition.

Humans

Driven toward care, avoiding the end: A systematic review and meta-analysis of the relationship between death anxiety and healthcare utilisation.

Both overuse and underuse of the healthcare system have been recognised as significant problems. Relatedly, growing research has recognised the key role of death anxiety in driving various health-relevant behaviours. However, the relationship between death anxiety and healthcare utilisation has not yet been systematically explored. The current systematic review and meta-analysis addressed this gap. In total, 987 papers were screened for inclusion, of which 63 were included in the final review (Ntotal = 21,271). This included 33 quantitative studies, 27 qualitative studies and 3 mixed-methods designs. In total, 17 studies contained sufficient data to be meta-analysed. Overall, the included studies highlighted a significant relationship between death anxiety and healthcare utilisation; in particular, positive associations with desire for life-prolonging treatments and contact with hospitals and medical professionals. By contrast, a negative association was found with other aspects of healthcare utilisation, including hospice use and end-of-life communication. The sample type emerged as a significant moderator, suggesting that the relationship between death anxiety and healthcare usage was strongest in non-medical samples. The current findings suggest that death anxiety plays a key role in utilisation of the healthcare system. The fear of death may need to be targeted in psychological interventions, in order to ensure maximal effectiveness of health services, and improve outcomes for healthcare users.

Humans

Advanced mitigation strategies for acrylamide formation in foods: Mechanistic insights, emerging innovations, and future perspectives.

Acrylamide is a heat-induced contaminant formed predominantly in carbohydrate-rich foods during high-temperature processing, posing significant concerns due to its potential carcinogenic, neurotoxic, and genotoxic effects. This review critically examines the mechanisms of acrylamide formation, emphasizing the role of the Maillard reaction and key precursors such as asparagine and reducing sugars, along with the influence of processing conditions including temperature, time, pH, and moisture. Various mitigation strategies are comprehensively discussed, ranging from raw material selection and genetic approaches to enzymatic treatments such as asparaginase and the application of natural and chemical inhibitors. Advances in processing technologies, including optimization of conventional thermal methods and emerging non-thermal techniques such as cold plasma and ultrasound, are evaluated for their effectiveness. The review also highlights the role of food additives, functional ingredients, and fermentation in reducing acrylamide formation. Furthermore, recent developments in analytical techniques, including chromatographic methods, biosensors, and artificial intelligence-based predictive models, are explored for improved detection and control. Risk assessment, toxicological implications, and global regulatory frameworks are also examined. Finally, future perspectives focusing on genetic engineering, personalized nutrition, and digital technologies such as AI and blockchain are discussed to support sustainable and industry-applicable mitigation strategies.

Acrylamide

Effects of Time-Based and Distance-Based Repeated Sprint Training on Physical and Physiological Adaptations in Collegiate Basketball Players.

PURPOSE: This study aimed to compare the effects of time-based (TB) and distance-based (DB) repeated-sprint training (RST) on athletic performance adaptations in collegiate basketball players during preseason and to examine whether the 2 training prescriptions produce different levels of homogeneity in the magnitude of individual adaptations. METHODS: Thirty young male basketball players (age = 21.3 [1.4]&#xa0;y) were randomly and equally assigned to 3 groups (n = 10): DB-RST, TB-RST, and an active control group. Participants completed a 7-week RST program performed 3 times per week, consisting of 4 sets of 4 to 9 repetitions per session. The DB-RST group completed each sprint by covering a fixed 35-m distance, whereas the TB-RST group performed each sprint maximally for a fixed 5-second duration. Performance assessments including countermovement vertical jump, 20-m sprint, Illinois change-of-direction speed, reactive strength index, Wingate anaerobic power, and cardiorespiratory fitness were conducted before and after the 7-week training period. RESULTS: Both training groups demonstrated significant performance improvements over the 7-week intervention and relative to the control group (P < .05). Similar gains were observed in the magnitude of adaptations in the countermovement vertical jump, 20-m sprint, Illinois change-of-direction speed, and reactive strength index for the DB-RST and TB-RST groups. Interestingly, the TB-RST group showed more gains than the DB-RST in the magnitude of adaptations in the peak and mean power outputs, as well as cardiorespiratory fitness. Moreover, the TB-RST group showed lower intersubject variability in adaptive responses across the measured performance outcomes following the training intervention. CONCLUSION: Our findings indicate that RST effectively enhances the performance of basketball players, and that implementing a TB-RST protocol is more effective than a DB-RST approach for producing greater adaptations in physiological variables-specifically anaerobic power output and cardiorespiratory fitness-over the 7-week preseason period.

Humans

Thyroid-joint crosstalk: a systematic review and meta-analysis of thyroid autoimmunity and dysfunction in juvenile idiopathic arthritis.

BACKGROUND: Recent observational studies outlined the concomitant presence of autoimmune diseases in children with juvenile idiopathic arthritis (JIA), including endocrine autoimmunity. Despite the growing evidence of thyroid involvement in JIA, available data are heterogeneous and fragmented. We aimed to systematically review the available evidence on the prevalence of thyroid autoantibody positivity and thyroid dysfunction in patients with JIA. METHODS: PubMed/Medline, Cochrane, and Scopus databases were approached to identify studies reporting data on thyroid autoantibody positivity and dysfunction in children with JIA. RESULTS: A total of 15 studies were included in the final analysis, encompassing 19 015 children with JIA (13 225 females, 69.6%) with a weighted mean age of 8.0 years (range 1.8-21 years). The pooled prevalence estimates of antithyroid antibody positivity and thyroid dysfunction were 0.04 (95% CI: 0.03-0.05) and 0.04 (95% CI: 0.03-0.08), respectively. The risk difference for thyroid autoantibody positivity between children with JIA and controls was 0.08 (95% CI: 0.02-0.14). Possible risk factors were analyzed: the presence of family history for thyroid autoimmune disease (odds ratio - OR 3.91, 95% CI 1.86-8.25), concurrent Antinuclear Antibodies (ANA) positivity (OR 1.62, 95% CI 1.13-2.31), and older age (MD 2.10 years, 95% CI 1.32-2.89) were associated with thyroid autoantibody positivity and/or thyroid dysfunction in children with JIA. No significant difference emerged for the specific JIA form. CONCLUSION: Thyroid dysfunction may be detected in children with JIA, with a significant risk difference in comparison to healthy controls. Specific clinical characteristics, such as family history, ANA positivity, and older age at JIA onset, may suggest which patients should benefit from thyroid autoantibody screening.

Humans

Joint association of sedentary behaviour and physical activity with cardiovascular disease: a systematic review and meta-analysis.

This systematic review and meta-analysis of cohort studies aimed to synthesize existing evidence on the joint association of physical activity (PA) and sedentary behaviour (SB) with cardiovascular disease (CVD) risk among adults. We searched PubMed, EMBASE, and Cochrane for English studies published between January 2010 and February 2025 that examined the joint association of PA and SB (fatal and non-fatal) CVD among adults and pooled their results through meta-analyses using study-level data. Using findings from 17 studies, the pooled effect size for the lowest PA + highest SB group was 1.78 (95% CI: 1.59-2.00), suggesting increased risk for CVD compared with the reference group (i.e. highest PA + lowest SB). Compared with the same reference group, we found an increased risk for CVD in the lowest PA + lowest SB (HR = 1.25, 95% CI: 1.12-1.40) and the highest PA + highest SB (HR = 1.16, 95% CI: 1.06-1.27) groups. Subgroup analyses according to domains or types of PA and SB exposure, outcome measures, and exposure measurement method revealed a similar pattern. In conclusion, individuals with the lowest PA combined with the highest SB may experience an increased risk for CVD events compared with those with the highest PA and lowest SB. There was also an increased risk for individuals with a combination of either low PA + low SB and high PA + high SB, albeit to a lesser extent. Although substantial study-level heterogeneity exists, the results highlight the potential value of considering both behaviours jointly in relation to CVD risk.

Humans

Systematic review of machine learning approaches for predicting sickle cell crisis and mortality risk at the climate-health nexus.

BACKGROUND: Sickle cell anemia (SCA) is a severe genetic blood disorder characterized by recurrent vaso-occlusive crises and increased mortality, with the greatest burden occurring in low- and middle-income countries. Climatic and environmental conditions, including temperature variability, humidity, rainfall, air pollution, and seasonal changes, have been associated with disease exacerbation. However, the extent to which these factors have been incorporated into predictive models remains unclear. This study systematically reviews the application of machine learning (ML) models for predicting SCA crises and mortality in relation to climate and environmental factors. METHODOLOGY: The PRISMA guidelines were used, and 34 peer-reviewed studies published between 2005 and 2026 were analyzed to identify the climate variables, ML approaches employed, and predictive performance. The reviewed studies applied a range of ML techniques, including artificial neural networks, random forests, support vector machines, decision trees, logistic regression, and deep learning models. Temperature, humidity, rainfall, wind speed, air quality indicators, and seasonal patterns were the most frequently examined environmental variables. RESULTS: The findings indicate that most existing models rely predominantly on clinical and demographic data, with limited integration of climate information and inadequate representation of high-burden regions, especially Sub-Saharan Africa. Studies incorporating environmental variables reported improved predictive performance and highlighted the potential of climate-informed early warning systems for SCA management. CONCLUSION: The review recommends development of interdisciplinary, climate-aware ML frameworks, expansion of longitudinal environmental datasets, and increased research in underrepresented regions to support climate-resilient and patient-centered SCA care.

Humans

How is goal setting used in interventions for chronic disease prevention and management in sub-Saharan Africa? A systematic review and narrative synthesis.

Non-communicable diseases are increasingly prevalent in sub-Saharan Africa, and goal setting is often used to promote healthy self-management behaviours. In this review, we aimed to synthesise literature around how goal setting is used, for application in future interventions in the region. A systematic search was conducted in six databases and results screened for eligibility. Study characteristics, intervention details, goal setting components, feedback from participants and facilitators were extracted. Data were analysed using narrative synthesis and thematic analysis. The Mixed Methods Appraisal Tool was used to assess study quality. We included 24 publications describing 18 unique interventions. Included studies were of high to moderate methodological quality. Goal setting intervention components were informed by a variety of frameworks and involved a range of tasks. Interventions were often facilitator-led; many were conducted in group settings. Participants reported goal setting as useful for putting self-management into practice but encountered challenges related to language and literacy levels. Adequate detail on goal setting intervention components was not always present. Through this review, we provide a comprehensive picture of the variability of goal setting approaches in chronic disease prevention and management in sub-Saharan Africa and recommend more standardised use and reporting of goal setting intervention components.

Humans

Does high fructose consumption trigger microglia activation and neuroinflammation? A systematic review.

This systematic review evaluated the effects of fructose intake on neuroinflammatory markers in rodent models. The search terms Fructose AND neuroinflammation OR Neurodegeneration OR chemokines OR interleukins OR microglia OR behaviour OR memory OR cognition were used in Google Scholar, Scopus and Web of Science. Thirteen animal studies investigating fructose-induced neuroinflammation that matched the eligibility criteria were included in the study. Across the studies, 16 inflammatory markers were identified and significantly altered following exposure to fructose. The findings consistently demonstrated elevated expression of pro-inflammatory cytokines, TNF-&#x3b1;, IL-6, and IL-1&#x3b2;, following fructose administration. Fructose consumption also dysregulated MCP-1, fractalkine, and CX3CR1 levels, thereby promoting inflammatory signalling and microglial activation. Furthermore, fructose exposure significantly increased IBA-1 and CD11b, indicating sustained neuroimmune activation. Alterations in important inflammatory pathways involving TLR4, NLRP3, NF-&#x3ba;B, MyD88, iNOS, and cyclooxygenases (COX-1 and COX-2) were also observed. In contrast, expression of the anti-inflammatory regulator peroxisome proliferator-activated receptor gamma (PPAR&#x3b3;) was reduced after fructose treatment. Overall, the findings suggest that chronic fructose consumption induces neuroinflammation through multiple inflammatory and immune-related mechanisms in the brain. These effects appear to be dose- and duration-dependent and may contribute significantly to neurodegeneration and cognitive impairment.

Microglia

Diagnostic performance of machine learning models versus established risk stratification for intracranial aneurysm rupture: a systematic review and bivariate meta-analysis.

BACKGROUND: Machine learning (ML) models have been proposed to improve the discrimination of intracranial aneurysm rupture status beyond established clinical risk stratification tools. However, reported performance is heterogeneous and the relative contribution of model architecture and feature dominance remains unclear. METHODS: We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-diagnostic test accuracy systematic review and diagnostic meta-analysis of studies evaluating ML models for intracranial aneurysm rupture discrimination. PubMed, Embase and CENTRAL were searched to February 2026. Sensitivity and specificity were pooled using a bivariate random-effects model, with summary receiver operating characteristic curves generated across training, internal testing and external validation datasets. Models were compared with regression-based approaches and Population, Hypertension, Age, Size of aneurysm, Earlier subarachnoid haemorrhage, Site of aneurysm (PHASES) scores. Subgroup and meta-regression analyses explored associations between algorithm family and feature domain. RESULTS: Sixty-two retrospective cohorts (29&#x2009;709 patients 209 models) met the inclusion criteria. In training datasets, pooled sensitivity and specificity for ML were 0.81 (95% CI 0.75 to 0.85)&#x2009;and 0.83 (0.80-0.86), with an area under the curve (AUC) of 0.878, exceeding PHASES (AUC 0.667). In testing datasets, ML retained higher discrimination (AUC 0.837) than regression models (0.806) and PHASES (0.646). In external validation, sensitivity was preserved (0.82), but specificity declined (0.66). Deep learning demonstrated the highest AUCs (training and testing). Incorporation of haemodynamic or radiomic features improved pooled discrimination relative to morphology alone. Evidence of small-study effects and mostly unclear Prediction Model Risk Of Bias Assessment Tool ratings were observed. CONCLUSIONS: ML approaches demonstrate higher pooled discrimination for aneurysm rupture status than conventional risk scores in retrospective datasets, but reduced external validation specificity and heterogeneity limit confidence for clinical translation. Prospective, externally validated, calibrated models are required before integration into routine cerebrovascular risk stratification.

Humans

Associations Between Health-Related Physical Fitness and Accelerometry-Based Energy Expenditure in Physiotherapy Workers.

BACKGROUND AND PURPOSE: Although it has been assumed that higher physical activity (PA) levels will contribute to better physical fitness (PF) performance, the interplay between these two has yet to be investigated. Moreover, the majority of studies have been presented in children and adolescents, and older adults, while little is known about the correlation in the adult working population of physiotherapists. Therefore, the main purpose of the study was to examine associations between objectively measured PA and health-related PF. METHODS: We recruited 50 physiotherapists (72.6% women) from several public and private settings in the city of Zagreb. The SenseWearArmbandPro3 (SWA), a triaxial accelerometer placed on the nondominant hand for 7 consecutive days, was used to capture total energy expenditure (TEE) and active EE (AEE). Cardiorespiratory fitness included the Harvard step test, and muscular fitness was composed of sit-ups in 60&#xa0;sec and the Handgrip strength. Flexibility was evaluated using the Toe-touch test. RESULTS: TEE and AEE were moderately and positively correlated with the Harvard step test (r&#xa0;=&#xa0;0.65 and 0.62, p&#xa0;<&#xa0;0.001), sit-ups (r&#xa0;=&#xa0;0.70 and 0.59, p&#xa0;<&#xa0;0.001), and the Handgrip strength test (r&#xa0;=&#xa0;0.74 and 0.64, p&#xa0;<&#xa0;0.001). No significant correlation with the Toe-touch test was observed (r&#xa0;=&#xa0;-0.25 and -0.19, p&#xa0;>&#xa0;0.05). When models were adjusted for age, weaker, but significant positive correlations remained. DISCUSSION: The findings suggest that both cardiorespiratory and muscular fitness are positively associated with PA, whereas no statistically significant association with flexibility was detected. Thus, it is not surprising that we obtained moderate to almost strong correlations between TEE and AEE with cardiorespiratory and muscular fitness. CONCLUSIONS: In physiotherapists, TEE and AEE yield moderate correlations with health-related PF, especially for cardiorespiratory and muscular fitness.

Humans

Multi-omics analysis reveals stage-associated differences in gut immunity and microbiota between juvenile and adult common carp (Cyprinus carpio).

In vertebrates, the development of intestinal immunity is closely associated with dynamic changes in the gut microbiota. However, stage-associated differences in intestinal immunity and gut microbial communities remain poorly characterized in teleost fish. In this study, transcriptomic analysis combined with 16S rRNA gene sequencing was employed to characterize intestinal immunity and gut microbial communities in juvenile and adult common carp (Cyprinus carpio). Transcriptomic profiling revealed marked developmental differences in intestinal immune function. Juvenile carp exhibited a predominantly innate immune phenotype, characterized by elevated expression of pro-inflammatory cytokines, antimicrobial peptides, and lysozyme-related genes. This immune profile was accompanied by enhanced mucosal barrier function and a relatively pro-inflammatory intestinal environment. In contrast, adult carp displayed increased expression of genes associated with adaptive immunity, suggesting that adult common carp exhibit relatively stronger adaptive immune characteristics than juvenile fish. Gut microbiota analysis demonstrated significant stage-dependent differences in microbial diversity and community composition. Juvenile fish were enriched with bacterial taxa potentially associated with innate immune activation, whereas adult fish harbored distinct microbial communities linked to intestinal homeostasis and barrier maintenance. Furthermore, correlation analyses identified significant associations between specific microbial taxa and innate immune-related gene expression, suggesting a close association between gut microbiota composition and intestinal immune characteristics in juvenile and adult common carp. Collectively, these findings reveal stage-associated differences in intestinal immunity and gut microbial communities between juvenile and adult common carp, thereby providing insights into intestinal immune characteristics at different developmental stages in teleost fish.

Animals

Short-term effects of foot reflexology on pain, anxiety, and physiological responses in women with shoulder and neck pain: A randomized controlled trial.

OBJECTIVES: Shoulder and neck pain (SNP) is a common musculoskeletal complaint among women and is often accompanied by heightened anxiety. Foot reflexology (FR) is a complementary therapy proposed to promote relaxation and short-term psychophysiological regulation. This study examined the short-term effects of a single session of FR on pain, anxiety, and physiological responses in women with SNP. METHODS: A single-blind randomized controlled trial was conducted with 80 women aged 20-64&#xa0;years in southern Taiwan. Participants were randomly allocated to one of three groups: FR, exercise, or passive rest control. Each group received a single 50-min session. Pain intensity and anxiety were assessed using the Numeric Rating Scale (NRS) and the State-Trait Anxiety Inventory (STAI), respectively. Heart rate and blood pressure were recorded as physiological indicators. Outcomes were measured at baseline, immediately post-intervention, and at 24-h follow-up. RESULTS: Baseline pain, anxiety, and physiological measures did not significantly differ among groups. Immediately after the intervention, both the FR and exercise groups demonstrated greater reductions in pain intensity compared with the passive rest control (P&#xa0;<&#xa0;0.001 and P&#xa0;=&#xa0;0.018, respectively). The FR group additionally showed greater reductions in anxiety and heart rate compared with the passive rest group (P&#xa0;=&#xa0;0.005 and P&#xa0;=&#xa0;0.001, respectively). Pain reduction in the FR group remained significant at the 24-h follow-up (P&#xa0;=&#xa0;0.013), whereas anxiety reductions were not sustained. No significant between-group differences were observed for systolic blood pressure. CONCLUSION: A single session of FR was associated with immediate and short-term reductions in pain, anxiety, and heart rate among women with SNP. Foot reflexology may serve as a supportive, non-pharmacological approach for short-term modulation, although sustained effects require further investigation.

Humans

Phytolacca acinosa Roxb. induces intestinal toxicity through the histamine-MLCK-tight junction axis: Integrated evidence from proteomics, metabolomics, intestinal organoids and epithelial barrier validation.

Phytolacca acinosa Roxb. (PR) is a saponin-rich medicinal plant associated with gastrointestinal toxicity, but the mechanisms underlying PR-induced intestinal barrier injury remain unclear. In this study, raw PR extract was analytically characterized by UPLC-ZenoTOF-MS/MS, confirming triterpenoid saponins as the predominant constituents. C57BL/6&#x202f;J mice were orally exposed to characterized PR extract (1.20 or 12.0&#x202f;g/kg for 5&#x202f;h), and Caco-2 cells and mouse intestinal organoids were used to assess epithelial toxicity and barrier disruption. Histopathology, ELISA, FITC-dextran permeability assays, immunofluorescence, CCK-8, LDH release, western blotting, DIA-based proteomics and untargeted metabolomics were integrated to define toxicological mechanisms. PR induced dose-dependent intestinal inflammation and barrier dysfunction, with the ileum as the most sensitive target. PR increased serum DAO and D-lactate and intestinal TNF-&#x3b1; and IL-1&#x3b2;, disrupted organoid morphology, enhanced epithelial permeability, and reduced ZO-1 expression. Proteomics revealed changes in inflammatory, lipid-metabolic, cytoskeletal and tight-junction pathways, including upregulation of MLCK3 and phospholipase-related proteins and downregulation of ZO-1 and ZO-2. Metabolomics identified histidine metabolism disturbance and histamine accumulation. Integrated multi-omics and pharmacological validation indicated that histamine activated the PLC/IP&#x2083;/Ca&#xb2;&#x207a;/CaM/MLCK cascade, promoting MLC phosphorylation, tight-junction disassembly and epithelial leakiness. MLCK inhibition partially restored ZO-1/ZO-2 expression and attenuated PR-induced epithelial injury. These findings identify the histamine-MLCK-tight junction axis as a key mechanism of PR-induced intestinal toxicity and support hazard identification of saponin-rich PR exposure.

Animals

Regional and statewide hysterectomy-corrected endometrial cancer incidence and five-year relative survival in Texas.

BACKGROUND: Rising endometrial cancer (EC) incidence nationwide, particularly among Hispanic women, and high prevalence of risk factors such as obesity and comorbidities in Texas, motivated us to estimate EC incidence rates (IRs) and survival by age (<50 years/ early-onset, &#x2265;50 years/late-onset), race-ethnicity (Non-Hispanic-White [NHW], -Black [NHB], Hispanic), histology (endometrioid, non-endometrioid), and area-based socioeconomic (SES) factors across Texas Health Service Regions (HSRs). STUDY DESIGN: Between 2000 and 2019, a total of 42,571 women (20-79 years) with EC were reported from Texas within the Surveillance, Epidemiology, and End Results Program. IRs and 5-year relative survival were calculated using SEER*Stat. IRs were corrected for hysterectomy using Behavioral Risk Factor Surveillance System data. RESULTS: Statewide EC IRs rose from 38.5 (2000-2009) to 44.5 (2010-2019), with the highest increase in the Upper-South (42.6 to 53.8). Across HSRs, Upper-South consistently had higher IRs among women <&#x202f;50 (13.9) and &#x2265;&#x202f;50 years (112.7). Among those <&#x202f;50 years, Hispanics had the highest IRs (12.4), predominantly endometrioid tumors, whereas in women &#x2265;&#x202f;50 years, NHB had the highest IRs (119.2) with a large proportion of non-endometrioid tumors. IRs were higher in areas with lower poverty, and higher education, income, and urbanization. Associations with unemployment were mixed. Worse survival outcomes were observed among NHBs, non-endometrioid, advanced-stage, and lower SES. Central Texas had more favorable survival outcomes compared to other HSR. CONCLUSION: EC IRs and survival rates in Texas largely mirror national trends, with regional differences likely reflecting sociodemographic and histologic distributions.

Humans