Search Results (1,039)

Background and Objectives: Emerging evidence indicates that individuals exposed to adverse childhood experiences (ACEs) face elevated risks for various chronic illnesses. However, the association between ACEs and osteoporosis risk remains underexplored, particularly regarding potential modifications by genetic susceptibility. This prospective cohort study aims to examine the relationship of ACEs with incident osteoporosis and investigate interactions with polygenic risk score (PRS). Materials and Methods: This study analyzed 124,789 UK Biobank participants initially free of osteoporosis. Cumulative ACE burden (emotional neglect, emotional abuse, physical neglect, physical abuse, sexual abuse) was ascertained through validated questionnaires. Multivariable-adjusted Cox proportional hazards models assessed osteoporosis risk during a median follow-up of 12.8 years. Moderation analysis examined genetic susceptibility interactions using a standardized PRS incorporating osteoporosis-related SNPs. Results: Among 2474 incident osteoporosis cases, cumulative ACEs showed dose–response associations with osteoporosis risk (adjusted hazard ratio [HR]_{per one-unit increase} = 1.07, 95% confidence interval [CI] 1.04–1.11; high ACEs [≥3 types] vs. none: HR = 1.26, 1.10–1.43). Specifically, emotional neglect (HR = 1.14, 1.04–1.25), emotional abuse (HR = 1.14, 1.03–1.27), physical abuse (HR = 1.17, 1.05–1.30), and sexual abuse (HR = 1.15, 1.01–1.31) demonstrated comparable effect sizes. Sex-stratified analysis revealed stronger associations in women. Joint exposure to high ACEs/high PRS tripled osteoporosis risk (HR = 3.04, 2.46–3.76 vs. low ACEs/low PRS) although G × E interaction was nonsignificant (P-interaction = 0.10). Conclusions: These results suggest that ACEs conferred incremental osteoporosis risk independent of genetic predisposition. These findings support the inclusion of ACE screening in osteoporosis prevention strategies and highlight the need for targeted bone health interventions for youth exposed to ACEs. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most prevalent chronic diseases in the world, lacking specific pharmacological interventions or well-established treatments. MASLD involves intricate pathological mechanisms characterized by oxidative stress and robust inflammatory responses. Selenium, an essential trace element, plays a critical role in antioxidation, regulation of inflammation, anticancer activity, and so on. Recent studies have reported that supplementation with selenium could alleviate MASLD and associated hepatic disorders, while excessive consumption may result in insulin resistance or even selenosis. Therefore, supranutritional selenium supplementation can be more suitable for the therapy and prevention of MASLD. This paper comprehensively reviews research about selenium and MASLD to highlight the potential applications and risks of supranutritional selenium supplementation in MASLD, following three steps: conducting a search, reviewing research articles and reviews, and discussing results. The keywords for the search include but are not limited to selenium, MASLD, supranutritional, hepatic diseases, selenoproteions, and selenium nanoparticles (SeNPs). We have reached the following conclusions: supranutritional selenium supplementation exhibits promising potential as a strategy to treat MASLD, but there are still some risks, depending on the dose and form of selenium; evaluating MASLD severity and selenium nutritional status accurately, as well as supplementing with superior forms of selenium (e.g., organic selenium and SeNPs), can further ensure the safety and efficacy of selenium supplementation. However, relationships between selenium homeostasis disorders and the occurrence and development of MASLD have not been fully elucidated. Methods for comprehensively assessing selenium status and mechanisms of selenosis require further investigation and research. Full article

Background: While timely blood transfusion is critical for restoring oxygen-carrying capacity after coronary artery bypass grafting (CABG), allogeneic blood product transfusions are independently associated with increased long-term mortality, necessitating a risk-stratified approach to balance oxygen delivery against immunological complications and infection risks. Methods: We retrospectively analyzed 3376 patients undergoing isolated CABG between 2005 and 2023 at a single tertiary center. Patients who died during their perioperative hospital stay within 30 days were excluded. Transfusion burden was assessed both as the absolute number of blood product units (packed red blood cells, platelet transfusion, fresh frozen plasma) and as a percentage of calculated patient blood volume. The primary outcome was all-cause mortality at 5 years. Flexible Cox regression with penalized smoothing splines, adjusted for EuroSCORE II, was used to model dose–response relationships. Results: From our cohort of 3376 patients, a total of 137 patients (4.05%) received >10 units of packed red blood cells (PRBC) perioperatively. These patients were older (median 71 vs. 68 years, p < 0.001), more often female (29% vs. 15%, p < 0.001), and had higher preoperative risk (EuroSCORE II: 2.53 vs. 1.41, p < 0.001). After 5 years, mortality was 42% in the massive transfusion group versus 10% in controls. Spline regression revealed an exponential increase in mortality with transfused units: 14 units yielded a 1.5-fold higher hazard of death (HR 1.46, 95% CI 1.31–1.64), rising to HR 2.71 (95% CI 2.12–3.47) at 30 units. When transfusion was indexed to blood volume, this relationship became linear and more tightly correlated with mortality, with lower maximum hazard ratios and narrower confidence intervals. Conclusions: Indexing transfusion burden to the percentage of patient blood volume replaced provides a more accurate and clinically actionable predictor of 5-year mortality after CABG than absolute unit counts. Our findings support a shift toward individualized, volume-based transfusion strategies to optimize patient outcomes and resource stewardship in a time of limited availability of blood products. Full article

The present study aims to investigate the multi-year effects (5 years) of individualized whole-body vibration (WBV) on locomotion, postural control, and handgrip strength in a 68-year-old man with relapse remitting multiple sclerosis (PwRRMS). The dose–response relationship induced by a single session was quantified by determining the surface electromyographic activity (sEMG) of the participant. The participant wore an orthosis to limit the lack of foot dorsiflexion in the weakest limb during walking in daily life. The gait alteration during walking was assessed at 1, 2 and 3 km/h (without the orthosis) through angle–angle diagrams by quantifying the area, perimeter and shape of the loops, and the sEMG of leg muscles was recorded in both limbs. The evaluation of postural control was conducted during upright standing by quantifying the displacement of the center of pressure (CoP). The handgrip strength was assessed by measuring the force–time profile synchronized with the sEMG activity of upper arm muscles. The participant improved his ability to walk at higher speeds (2–3 km/h) without the orthosis. There were greater improvements in the area and perimeter of angle–angle diagrams for the weakest limb (Δ = 36–51%). The sEMG activity of the shank muscles increased at all speeds, particularly in the tibialis anterior of weakest limbs (Δ = 10–68%). The CoP displacement during upright standing decreased (Δ = 40–60%), whereas the handgrip strength increased (Δ = 32% average). Over the 5-year period of intervention, the individualized WBV improved locomotion, postural control and handgrip strength without side effects. Future studies should consider the possibility of implementing an individualized WBV in PwRRMS. Full article

Botulinum neurotoxin-A (BoNT-A) injections are effective in reducing focal limb spasticity; however, their impact on strength and active function needs to be established. This review was a secondary analysis aimed at evaluating changes to active function in the context of muscle strength changes following BoNT-A intramuscular injection for adult upper and lower limb spasticity. The original review searched eight databases (CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Google Scholar, MEDLINE, PEDro, PubMed, Web of Science) and was conducted with methodology that followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines as described in section 6.2 of Gill et al. For this secondary analysis, no databases were searched; only further data were extracted. The current and preceding review were registered in the Prospective Register of Systematic Reviews (PROSPERO: CRD42022315241). Twenty studies were screened for inclusion, and three studies were excluded because active function was not assessed in all participants. Seventeen studies (677 participants) met the inclusion criteria for analysis. Quality was examined using the PEDro scale and modified Downs and Black checklist and rated as fair to good. Pre- and post-BoNT-A injection strength (agonist, antagonist, and global), active function (activity), participation, and quality-of-life outcomes at short-, mid-, and long-term time points were extracted and analysed. Significant heterogeneity and limited responsiveness in strength and active function outcome measures limited the ability to determine whether changes in strength mediate an effect on active function. Further, variability in BoNT-A type and dose, adjunctive therapies provided, and variability in reporting limited analyses. Overall, no clear relationship existed between the change in muscle strength and active function following BoNT-A injections to the upper and lower limbs for focal spasticity in adult-onset neurological conditions. Full article

Recent breakthroughs in cancer immunotherapy have shown remarkable success, yet treatment efficacy varies significantly among individuals. Emerging evidence highlights the gut microbiota as a key modulator of immunotherapy response, while vitamin D (VD), an immunomodulatory hormone, has garnered increasing attention for its potential interactions with gut microbiota and immunotherapy outcomes. However, the precise mechanisms and clinical applications of VD in this context remain controversial. This study systematically analyzed peer-reviewed evidence from PubMed, Scopus, Web of Science, PsycINFO, and MEDLINE (January 2000–May 2025) to investigate the complex interplay among VD, gut microbiota, and cancer immunotherapy. This review demonstrates that VD exerts dual immunomodulatory effects by directly activating immune cells through vitamin D receptor (VDR) signaling while simultaneously reshaping gut microbial composition to enhance antitumor immunity. Clinical data reveal paradoxical outcomes: optimal VD levels correlate with improved immunotherapy responses and reduced toxicity in some studies yet are associated with immunosuppression and poorer survival in others. The bidirectional VD–microbiota interaction further complicates this relationship: VD supplementation enriches beneficial bacteria, which reciprocally regulate VD metabolism and amplify immune responses, whereas excessive VD intake may disrupt this balance, leading to dysbiosis and compromised therapeutic efficacy. These findings underscore the need to elucidate VD’s dose-dependent and microbiota-mediated mechanisms to optimize its clinical application in immunotherapy regimens. Future research should prioritize mechanistic studies of VD’s immunoregulatory pathways, personalized strategies accounting for host–microbiota variability, and large-scale clinical trials to validate VD’s role as an adjuvant in precision immunotherapy. Full article

Climate change and air pollution are reshaping viral circulation patterns and increasing host vulnerability, amplifying the burden of respiratory illness in early childhood. This narrative review synthesizes current evidence on how environmental exposures, particularly to nitrogen dioxide, ozone, and fine particulate matter, contribute to the incidence and severity of bronchiolitis, with a focus on biological mechanisms, epidemiological trends, and public health implications. Bronchiolitis remains one of the leading causes of hospitalization in infancy, with Respiratory Syncytial Virus (RSV) being responsible for the majority of severe cases. Airborne pollutants penetrate deep into the airways, triggering inflammation, compromising mucosal defenses, and impairing immune function, especially in infants with pre-existing vulnerabilities. These interactions can intensify the clinical course of viral infections and contribute to more severe disease presentations. Children in urban areas exposed to high levels of traffic-related emissions are disproportionately affected, underscoring the need for integrated public health interventions. These include stricter emission controls, urban design strategies to reduce exposure, and real-time health alerts during pollution peaks. Prevention strategies should also address indoor air quality and promote risk awareness among families and caregivers. Further research is needed to standardize exposure assessments, clarify dose–response relationships, and deepen our understanding of how pollution interacts with viral immunity. Bronchiolitis emerges as a sentinel condition at the crossroads of climate, environment, and pediatric health, highlighting the urgent need for collaboration across clinical medicine, epidemiology, and environmental science. Full article

Background/Objectives: Substance use disorders, particularly opioid addiction, continue to pose a major global health and toxicological challenge. Morphine dependence represents a significant problem in both clinical practice and preclinical research, particularly in modeling the pharmacodynamics of withdrawal. Rodent models remain indispensable for investigating the neurotoxicological effects of chronic opioid exposure and withdrawal. However, conventional behavioral assessments rely on manual observation, limiting objectivity, reproducibility, and scalability—critical constraints in modern drug toxicity evaluation. This study introduces MWB_Analyzer, an automated and high-throughput system designed to quantitatively and objectively assess morphine withdrawal behaviors in rats. The goal is to enhance toxicological assessments of CNS-active substances through robust, scalable behavioral phenotyping. Methods: MWB_Analyzer integrates optimized multi-angle video capture, real-time signal processing, and machine learning-driven behavioral classification. An improved YOLO-based architecture was developed for the accurate detection and categorization of withdrawal-associated behaviors in video frames, while a parallel pipeline processed audio signals. The system incorporates behavior-specific duration thresholds to isolate pharmacologically and toxicologically relevant behavioral events. Experimental animals were assigned to high-dose, low-dose, and control groups. Withdrawal was induced and monitored under standardized toxicological protocols. Results: MWB_Analyzer achieved over 95% reduction in redundant frame processing, markedly improving computational efficiency. It demonstrated high classification accuracy: >94% for video-based behaviors (93% on edge devices) and >92% for audio-based events. The use of behavioral thresholds enabled sensitive differentiation between dosage groups, revealing clear dose–response relationships and supporting its application in neuropharmacological and neurotoxicological profiling. Conclusions: MWB_Analyzer offers a robust, reproducible, and objective platform for the automated evaluation of opioid withdrawal syndromes in rodent models. It enhances throughput, precision, and standardization in addiction research. Importantly, this tool supports toxicological investigations of CNS drug effects, preclinical pharmacokinetic and pharmacodynamic evaluations, drug safety profiling, and regulatory assessment of novel opioid and CNS-active therapeutics. Full article

Objective: Tumor progression is regulated by systemic immune status, nutritional metabolism, and the inflammatory microenvironment. This study aims to investigate inflammatory–nutritional biomarkers associated with metachronous liver metastasis (MLM) in colorectal cancer (CRC) and develop a machine learning model for accurate prediction. Methods: This study enrolled 680 patients with CRC who underwent curative resection, randomly allocated into a training set (n = 477) and a validation set (n = 203) in a 7:3 ratio. Feature selection was performed using Boruta and Lasso algorithms, identifying nine core prognostic factors through variable intersection. Seven machine learning (ML) models were constructed using the training set, with the optimal predictive model selected based on comprehensive evaluation metrics. An interactive visualization tool was developed to interpret the dynamic impact of key features on individual predictions. The partial dependence plots (PDPs) revealed a potential dose–response relationship between inflammatory–nutritional markers and MLM risk. Results: Among 680 patients with CRC, the cumulative incidence of MLM at 6 months postoperatively was 39.1%. Multimodal feature selection identified nine key predictors, including the N stage, vascular invasion, carcinoembryonic antigen (CEA), systemic immune–inflammation index (SII), albumin–bilirubin index (ALBI), differentiation grade, prognostic nutritional index (PNI), fatty liver, and T stage. The gradient boosting machine (GBM) demonstrated the best overall performance (AUROC: 0.916, sensitivity: 0.772, specificity: 0.871). The generalized additive model (GAM)-fitted SHAP analysis established, for the first time, risk thresholds for four continuous variables (CEA > 8.14 μg/L, PNI < 44.46, SII > 856.36, ALBI > −2.67), confirming their significant association with MLM development. Conclusions: This study developed a GBM model incorporating inflammatory-nutritional biomarkers and clinical features to accurately predict MLM in colorectal cancer. Integrated with dynamic visualization tools, the model enables real-time risk stratification via a freely accessible web calculator, guiding individualized surveillance planning and optimizing clinical decision-making for precision postoperative care. Full article

Using the behavioral model of engagement in health services, the current study assessed client characteristics that may contribute to treatment duration in trauma-focused psychotherapy in a community clinic setting. Participants (n = 893) were adults ages 18–78 years old (M = 36.36, SD 12.37). Demographic data (e.g., age, income) and health profile questionnaires assessing trauma and depression symptoms were collected at intake and every three sessions thereafter to track health outcome progress. Logistic regression models assessed factors associated with treatment duration at three time points: treatment initiation (0–2 sessions), treatment engagement (3–5 sessions), and treatment sustainment (6–8 sessions). For this sample, 38.6% ended treatment at the treatment initiation phase. Lower education level and higher quality of social relationships was predictive of ending treatment. In the engagement phase, 29.2% of the remaining participants (n = 548) ended treatment before six sessions, but there were no predictors of ending. During the sustainment phase, 31.7% ended treatment. African American race was associated with ending at this phase. In total, 70.3% of participants ended treatment before nine sessions. Participants who remained in treatment through the sustainment phase showed significant improvement in trauma and depression symptoms at each of the previous treatment phases, providing evidence of a dose response effect. Lower education, higher quality of social relationships, and African American race were associated with leaving treatment early. Many participants ended treatment before nine sessions, but those that completed treatment experienced improvement in symptoms to sub-clinical levels. Full article

The management of end-stage kidney disease (ESKD) poses a substantial clinical and economic challenge, characterized by a growing patient burden, rising healthcare costs, and persistent unmet needs to enhance survival outcomes and quality of life. Background/Objectives: Conventional high-flux hemodialysis (HD) remains the dominant form of renal replacement therapy for ESKD but is still associated with substantial morbidity and mortality. High-volume post-dilution online hemodiafiltration (HVHDF) offers a promising alternative by enhancing the convective removal of uremic toxins. Methods: We conducted a narrative review of randomized controlled trials, meta-analyses, real-world cohort studies, and registry analyses published between 2010 and 2024. Evidence was categorized into short-term, medium-term, and long-term outcomes, including hemodynamic stability, inflammation, anemia, infection risk, cardiovascular events, cognitive decline, quality of life, and survival. Results: HVHDF improves short-term outcomes by enhancing toxin clearance, stabilizing blood pressure, reducing inflammation and oxidative stress, and improving anemia management. Medium-term benefits include improved nutritional status, reduced hospitalizations related to infections, and improved neurological and immune function. Long-term data from major trials (e.g., ESHOL, CONVINCE) and large real-world studies show consistent reductions in all-cause and cardiovascular mortality, particularly with convection volumes ≥ 23 L/session. A clear dose–response relationship supports the clinical relevance of convection volume targets. HVHDF has also shown benefits in preserving cognitive function and enhancing health-related quality of life. Conclusions: Strong and converging evidence supports HVHDF as a superior dialysis modality. Given its survival benefits, better tolerance, and broader impact on patient outcomes, HVHDF should be considered the new standard of care in dialysis, especially in light of the recent regulatory approval of the machine that provides the ability to perform HDF in the United States. Full article

Polyethylene (PE) is the most widely produced plastic globally. It is extensively used as packaging in both the food and pharmaceutical industries. Its use can result in the formation of emerging contaminants—microplastics (MPs). This review summarizes current knowledge on PE and PE-derived microplastics (PE–MPs) and highlights existing gaps. It discusses the factors influencing PE degradation, with particular emphasis on interactions with packaged contents and food products. The role of PE–MPs as vectors for environmental contaminants is also examined, focusing on their adsorption and desorption behavior. Finally, we explore the toxicity and bioaccessibility of PE–MPs. Our findings indicate that pH, temperature, and exposure time are the most significant factors driving PE degradation. However, comparative studies examining a broad spectrum of parameter values remain scarce. The process of PE–MP generation remains largely unexplored. Adsorption mechanisms on PE–MPs are well documented in the literature. In contrast, desorption has received significantly less scientific attention, and its relevance to human exposure is still unclear. Numerous studies have suggested potential links between human exposure to PE–MPs and the development of non-communicable diseases, including cardiovascular and neurodegenerative disorders. Nevertheless, no studies have yet examined the bioavailability of PE–MPs. Similarly, the dose-response relationship between PE and MP exposure and toxicological outcomes in humans remains unclear. As a result, it is currently not possible to establish safety thresholds for PE–MP contamination in food products. This review offers a novel polymer-specific approach to MPs research and outlines specific recommendations for future studies. Full article

Background: Although B vitamins are implicated in cardiovascular regulation, the associations between serum thiamine (vitamin B1) and blood pressure (BP) remain unclear, particularly among women who are at high risk for hypertension-related complications. This study aimed to investigate relationships between serum thiamine levels and BP outcomes among middle-aged and elderly women in eastern China. Methods: A community-based cross-sectional study was conducted among 2015 women aged 45–69 years in Zhejiang Province, China. Serum thiamine levels were quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS). Hypertension was defined as measured BP ≥ 140/90 mmHg, or current use of antihypertensive medications. Multivariate logistic and linear regression models were used to assess associations of thiamine with hypertension prevalence and BP levels, respectively. Dose–response relationships were evaluated using restricted cubic splines (RCSs). Results: Higher thiamine levels were significantly associated with reduced hypertension prevalence (adjusted OR per SD increase: 0.87; 95%CI: 0.77, 0.97), with RCSs confirming linear dose–response (p-overall < 0.05, p-nonlinearity > 0.05). Compared with the lowest tertile, participants in the highest thiamine tertile had a 25% lower hypertension risk. Thiamine levels also showed negative associations with systolic BP (adjusted coef: −1.51 mmHg per SD; 95% CI: −2.33, −0.68), with the participants in the highest tertile showing a 3.94 mmHg reduction (95%CI: −5.97, −1.92). No significant relationship was found for diastolic BP. Conclusions: Serum thiamine is inversely associated with both hypertension prevalence and systolic BP in middle-aged and elderly women. This study supports the potential of serum thiamine as a modifiable biomarker in hypertension prevention strategies, particularly among aging women. Full article

Environmental tobacco smoke (ETS) exposure is a public health concern linked to neurodevelopmental disorders like attention deficit hyperactivity disorder (ADHD). Prior studies link ETS to ADHD, but gaps remain regarding gender differences, critical exposure windows, and dose–response relationships. This study assessed ETS exposure’s association with ADHD-like behaviors in Chinese preschoolers, evaluating overall risk, critical periods, dose–response relationships, and gender differences. Analyzing data from 64,472 preschoolers, ETS exposure (prenatal; infancy, 0–1; and early childhood, 1–3 years) was assessed via parent questionnaires, and ADHD-like behaviors were measured using the Conners’ Parent Rating Scale-Revised, with associations examined via logistic regression. ETS-exposed children had a 49% higher ADHD-like behavior risk (AOR = 1.49, 95% CI: 1.38–1.62, p < 0.001), with dose–response effects: The risk increased from AOR = 1.25 (95% CI: 1.10–1.40) at low exposure to 2.24 (95% CI: 1.63–3.01) at high exposure. Prenatal (AOR = 1.42, 95% CI: 1.17–1.71) and infancy exposures (AOR = 1.43, 95% CI: 1.05–1.90) showed the strongest associations, while early childhood exposure (1–3 years) was non-significant (AOR = 1.04, 95% CI: 0.82–1.29). No gender-specific differences were observed. Early-life ETS exposure, particularly prenatally and in infancy, elevates ADHD-like behavior risk in preschoolers, demonstrating dose–response trends without gender disparity, highlighting the need for universal strategies to reduce such exposures. Full article

Regional increases in atmospheric O₃ are phytotoxic not only to major crops but also to root vegetables such as radish, and their effects can be further modulated by nitrogen (N) addition. To assess how cherry radish responds to elevated O₃ (eO₃) under N addition and to compare the dose–response relationships, we established six open-top chambers with two O₃ levels and two N treatments in Beijing, China, to examine gas exchange, growth, and biomass throughout the growing period. The results showed that: 1. eO₃ had a “priming effect” on photosynthesis rates (Pn) at the beginning of the experiment. N addition alleviated the O₃-induced Pn reduction at the end of the experiment by 6.76% but did not significantly influence the O₃-dose response to Pn; 2. stomatal conductance (gs) did not have a dose response to all treatments while evaporation rates (E) showed strong negative regression with AOT40; 3. N addition reduced the hypocotyl biomass (−47.70%), leaf biomass (−32.22%), and the whole plant biomass reduction caused by O₃ (−38.47%) at the end of the experiment, but N addition did not significantly influence O₃-dose response to biomass. In conclusion, N addition can alleviate O₃-induced reductions in Pn and biomass via non-stomatal mechanisms, but it is ineffective in altering long-term O₃ dose–response relationships. Soil N addition offers a short-term strategy to mitigate O₃ impacts on short-lived root vegetables such as cherry radish but does not influence key functional traits over the long term. This study highlights the potential of N addition to alleviate acute oxidative stress, while underscoring its limitations in mitigating the effects of prolonged O₃ exposure in root vegetables. Full article