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PubMed2026

Game-Based Intervention for Bullying: Assessing the Efficacy of the REThink Therapeutic Game in Primary School Children.

Children's mental health issues can have a lasting effect into adulthood, including enhanced risks for their social and emotional development, as well as their academic performance and overall behavior. Worldwide nearly 1 billion children are affected by the bullying phenomenon, with social, emotional, and economic consequences. In this vein, our study aimed to analyze the effect of the therapeutic game REThink on the improvement of emotion regulation abilities and the reduction of both bullying behavior and victimization in primary school children. Our sample consisted of 75 children who were voluntarily enrolled by their parents, and randomly assigned to the intervention group (n = 38) or to the control group (n = 37). They completed the baseline assessment consisting of emotion regulation, irrationality, bullying and victimization behavior measurements, then the children from the intervention group played the therapeutic game REThink. Four weeks later, after completing each level twice, every participant had completed the same questionnaires at the post-test assessment. The results indicated significant changes across victimization for children who were exposed to verbal, physical or social bullying, increased emotional control and lower levels of irrationality, low frustration tolerance to work and demandingness, with small to medium effect size improvements for the REThink game group compared to the control group. The REThink therapeutic game proved to be a promising intervention tool for reducing victimization effects and irrationality, and improving emotion regulation abilities in primary school children. Future research could improve on these results by addressing the timeline stability limit.

Humans↗

PubMed2026

Muscle Massage Adding Capacitive Resistive Electric Transfer Therapy in Active or Sham Condition for Post-Exercise Recovery in Athletes: A Crossover Clinical Trial.

The increasing demands of elite sports reduce recovery time, impair performance, and increase injury risk. Efficient lactate transport is essential for postexercise recovery. Capacitive resistive electric transfer (CRET) therapy enhances deep tissue heating, induces vasodilation, and promotes circulation. To evaluate whether adding active CRET to a standardized muscle recovery massage, compared with the same massage plus sham CRET, influences indicators of muscle recovery following a maximal anaerobic effort test. A randomized, single-blind, sham-controlled, and crossover clinical trial was conducted in 25 athletes. Participants completed four visits and, after the maximal power and anaerobic capacity test (Wingate test), received a standardized muscle recovery massage combined with either active CRET or sham CRET. Blood lactate levels, muscle oxygenation, muscle thickness, echogenicity, knee extension force, and muscle activity were assessed before and after the test, after treatment, and 24 hours later. Compared with massage plus sham CRET, massage plus active CRET was associated with lower blood lactate concentration at 60 min postexercise (p = 0.029). Ultrasound-derived muscle thickness and echogenicity also differed between conditions at several time points (p < 0.05). However, no significant differences were observed in Wingate test performance, force, muscle activity, and oxygenation between conditions. In athletes performing repeated Wingate exercise, adding active CRET to massage was associated with lower blood lactate concentration at 60 min postexercise and with differences in ultrasound-derived muscle thickness and echogenicity compared with sham CRET plus massage. However, these between-condition differences were not accompanied by clear short-term functional recovery benefits. TRIAL REGISTRATION: NCT06906146.

Humans↗

PubMed2026

Prognostic effect of serum glial fibrillary acidic protein and neurofilament light chain for predicting progression independent of relapse activity in multiple sclerosis: A systematic review.

BACKGROUND: Progression independent of relapse activity (PIRA) is increasingly appreciated as one of the important factors contributing to disability accumulation in MS. sGFAP and sNfL could represent markers reflecting two separate biological processes related to relapse-independent progression in MS. OBJECTIVE: To perform a systematic review of the literature on blood GFAP and/or NfL measured in relation to PIRA or other similar relapse-independent progression endpoints in people with MS. METHODS: PubMed, Scopus, and Web of Science databases were searched from inception to 1 June 2026. The eligible studies were original human studies measuring blood GFAP and/or NfL concentrations in serum, plasma, or any other type of blood-derived material and assessing PIRA, PIRMA, CDP/CDW without relapses, relapse-free EDSS progression, non-inflammatory progression, or comparable relapse-independent disability worsening outcomes. Methodological quality was assessed according to the Newcastle-Ottawa scale and the QUIPS instrument for bias detection in the body of evidence on prognostic factors. Due to heterogeneity of outcomes, biomarker measurements and effect estimates, results were synthesized qualitatively rather than quantitatively. RESULTS: After removing duplicates, 1206 records were screened, followed by full-text review of 120 reports. A total of 18 reports were included. Overall, sGFAP was associated more frequently with PIRA or PIRA-like disability progression, particularly in cohorts with suppressed or limited overt inflammatory activity. Evidence for sNfL was more variable and context-dependent: several studies reported associations with PIRA-like or relapse-independent disability worsening when acute inflammatory activity was absent, suppressed, or analytically separated, whereas other studies reported negative or inconclusive findings. Negative or inconclusive results were reported by several articles, particularly when broad outcomes were evaluated or the study population was small. CONCLUSION: Blood GFAP and NfL give complementary but non-interchangeable information concerning PIRA in MS patients. The existing evidence base does not allow us to perform meta-analysis because of heterogeneity in terms of outcomes, standardization of biomarkers, and treatment context. Further prospective investigations with uniform criteria will be necessary for their use as biomarkers of PIRA in clinical settings.

Humans↗

PubMed2026

Tripled-Stranded Antisense Oligonucleotide for Biomarker-Activated Suppression of Essential Genes.

Conditional activation of antisense oligonucleotides (ASOs) is a promising strategy for selective suppression of cancer cells without affecting normal cells. In this study, we developed a tripled-stranded ASO (tsASO) that is rendered inactive through complexation with two additional oligonucleotides. The key innovation is the use of partial overlap between the parent ASO and the biomarker sequence, combined with toehold-mediated strand displacement, enabling precise conditional activation. The tsASO effectively triggered RNase H-mediated degradation of DYNC1I2 and DARS1 RNAs exclusively in the presence of the ERBB2 sequence. In cell-free systems, the tsASO demonstrated high cleavage efficiency (up to 81%), comparable to the parent ASO efficiency, with minimal background activity in the absence of the biomarker sequence, validating the concept at the molecular level. However, in cells using lipid-based transfection, the tsASO exhibited nonspecific cytotoxicity that did not correlate with biomarker presence or target gene expression. Detailed analysis showed no clear support for known sequence-driven toxicity mechanisms (CpG/TLR9, G-quadruplexes) in the nonimmune cell lines, suggesting that the primary limitation is intracellular delivery rather than the tsASO design. Future work should focus on optimizing delivery platforms to achieve controlled cellular uptake and biomarker-dependent release, unlocking the therapeutic potential of this conditional gene silencing approach.

Oligonucleotides, Antisense↗

PubMed2025

A Systematic Review of Quantitative Studies of Depression and Loneliness in Black Women with Hypertension in the United States.

INTRODUCTION: Hypertension disproportionately affects Black women with subsequent complications that can extend beyond physical health. Notably, there is a significant relationship between hypertension, depression, and loneliness, with hypertensive Black women more likely to exhibit symptoms of depression. Since loneliness and social isolation are predictors of depression, recognizing and addressing these interconnected health concerns could improve patient outcomes and quality of life. This systematic review presents a synthesis of findings on depression screening practices, depression symptoms, and loneliness in quantitative studies of Black women with hypertension in the United States. METHODS: Using the EbscoHost platform, a comprehensive literature search for studies measuring depression and loneliness in Black women with hypertension was conducted. The following databases were selected: Medline Complete, CINAHL Complete, APA PsychArticles, and PsychINFO. RESULTS: Twenty-three articles were included; 16 focused on depression, and these studies highlighted a significant burden of depression in this demographic compared to their counterparts. Five studies reported loneliness and its relation to depression and hypertension. Loneliness and social isolation, as independent risk factors, exacerbated symptoms of depression and contributed to the onset and progression of hypertension. Two prior reviews corroborated these findings. Studies have emphasized the role of trust in clinical interactions and the importance of appropriate therapeutic interventions. DISCUSSION: Black women with hypertension are at a heightened risk for symptoms of depression, compounded by feelings of loneliness. Loneliness and depression are linked to physiological stress, contributing to hypertension. These problems are underrecognized and undertreated across populations, and this lack of recognition and treatment contributes to health inequity.

Humans↗

PubMed2026

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-α, IL-6, and IL-1β, 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-κB, 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 (PPARγ) 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↗

PubMed2026

Blood Bile Acids for Inflammatory Bowel Disease Diagnosis and Disease Activity Assessment: A Metabolomics Meta-Analysis.

Alterations in circulating bile acids (BAs) have been reported in inflammatory bowel disease (IBD), but the consistency of these changes across clinically relevant comparisons remains unclear. Our goal was to investigate systemic BA alterations in IBD using a metabolomics meta-analysis with an exploratory analysis of BA-related gene expression as a supporting context. A systematic review and meta-analysis of 28 metabolomics studies examined blood BA profiles associated with IBD, IBD diagnosis, and disease activity assessment. Univariate analysis and logistic regression modeling of two independent IBD cohorts explored the blood BA-related genes and IBD. Across 28 studies that comprised 5056 IBD patients, 1721 healthy controls, and 314 non-IBD patients, 131 BAs were reported. Eight predefined clinical comparisons were eligible for the meta-analysis. Lower secondary BA levels were consistently observed in IBD patients compared with controls, between UC and CD, and in active versus remission patients. Deoxycholic acid, glycodeoxycholic acid, and taurodeoxycholic acid were frequently decreased, whereas glycocholic acid was increased in certain comparisons. Transcriptomics analyses revealed differential expression of several BA-related genes in blood, including SLC51A, ABCB4, and ACOT8, across the comparisons. Our findings identify consistent circulating BA alterations in IBD and highlight the relevance of blood BA for future biomarker research in the diagnosis and disease activity assessment.

Humans↗

PubMed2026

Activity of Aztreonam-avibactam and Ceftazidime-Avibactam against Enterobacterales and Pseudomonas aeruginosa causing infections in patients hospitalized in hematology, oncology, and transplant units from United States medical centres (2019-2024).

Immunosuppression increases the risks and severity of infections and is associated with a higher incidence of infection with multidrug-resistant (MDR) pathogens. We evaluated the antimicrobial susceptibility of Enterobacterales and Pseudomonas aeruginosa from patients hospitalized in hospital units where the frequency of immunosuppressed patients is very high. Bacterial isolates were consecutively collected (1/patient) from 75 US medical centres in 2019-2024 and susceptibility tested by broth microdilution. Enterobacterales (n = 2,407) and P. aeruginosa (n = 485) from patients hospitalized in hematology, oncology, and transplant units were evaluated. Carbapenem-resistant Enterobacterales (CRE) were screened for β-lactamases by whole genome sequencing. Enterobacterales were mainly from bloodstream infection (BSI; 53.6%) and urinary tract infection (19.9%) and P. aeruginosa were mainly from BSI (37.9%) and pneumonia (35.0%). Aztreonam-avibactam, ceftazidime-avibactam, and meropenem-vaborbactam were highly active against Enterobacterales (99.9-99.4% susceptible), including MDR isolates (99.6-98.1% susceptible), but only aztreonam-avibactam exhibited good activity against CRE (95.8% susceptible). Ceftolozane-tazobactam showed good activity against Escherichia coli (95.7% S) and Klebsiella pneumoniae (92.8% S), but limited activity against Enterobacter cloacae species complex (75.9% susceptible). All (100.0%) carbapenemase (CBase)-producing CRE isolates were aztreonam-avibactam-susceptible while 77.4% were ceftazidime-avibactam-susceptible and 67.7% were meropenem-vaborbactam-susceptible. The most common CBases were KPC (41.7%), NDM (12.5%), and OXA-48 types (10.4%). Metallo-β-lactamases represented 23.5% of CBases and were identified in 16.7% of CREs. The most active agents against P. aeruginosa were ceftazidime-avibactam (95.7% susceptible), ceftolozane-tazobactam (94.8% susceptible), and tobramycin (91.5% susceptible). Piperacillin-tazobactam and meropenem were active against 81.4% and 82.5% of P. aeruginosa, respectively, and aztreonam-avibactam inhibited 78.6% of P. aeruginosa at ≤8 mg/L.

Humans↗

PubMed2025

Predictive Validity of Violence Screening Tools in Emergency and Psychiatric Services: A Systematic Review.

Violence against healthcare staff, including a threat or an act of violence toward people during their work, poses a physical and psychological risk to workers internationally. Screening is an important strategy in preventing violence against healthcare professionals. The aim of this systematic review was to synthesize evidence on the predictive validity of risk assessment tools used to screen for violence and aggression risk toward healthcare workers in emergency and psychiatric departments (PD). Primary studies that examined the predictive validity of risk assessment tools for workplace violence were identified via a systematic search of Medline, PsycINFO, Embase, and the Cochrane databases. There were 62 eligible studies, ten of which had a lower risk of bias (RoB). Those studies with high RoB were primarily due to a failure to present calibration measures as part of the analysis. All included studies adopted a longitudinal design and were conducted in PDs. The ten highest-quality studies reported on eight different instruments, four of which showed acceptable to outstanding predictive performance. The Dynamic Appraisal of Situational Aggression and the Brøset Violence Checklist showed the best predictive performance; they were also validated in emergency departments and are best suited for short-term risk prediction. We recommend that the selection of a risk assessment tool should consider the following: (a) the target population, (b) the violence operationalization, and (c) the purpose of the monitoring. We note that the use of a screening tool should be a part of a multicomponent strategy to ensure staff safety.

Humans↗

PubMed2026

Structural and physicochemical characterisation of branched dextrans produced by an active α-(1→2) branching sucrase from Apilactobacillus kunkeei PDER37.

Recently, branching sucrases encoded in the genomes of certain Lactic Acid Bacteria (LAB) strains have become novel enzymes to obtain branched α-glucans. In this study an active α-(1 → 2) branching sucrase from Apilactobacillus kunkeei PDER37 was expressed, characterised and distinct branched dextrans was obtained with reactions under different sucrose: dextran ratio. Structural characterisation by 1H and 13C NMR analysis demonstrated the branching of the dextran with (1 → 2)-linked α-d-glucose units with no alteration in the final structure depending on sucrose: dextran ratio (D0) but this ratio was effective for the determination of the molecular weights of the branched dextrans (D1, D2 and D3). FTIR analysis further supported the dextran structures and suggested the higher accumulation of the α-Glc units in the branched dextrans. Thermal characterisation of the branched dextrans obtained by TGA and DSC analysis suggested the increased hygroscopicity of the branching units. Both SEM and AFM analysis demonstrated more porous chain like structures in the branched dextrans. This study provides valuable information on the role of active α-(1 → 2) branching sucrase (BS37) for the production of branched dextrans with potential increased physicochemical status applicable for food and other industries.

Dextrans↗

PubMed2026

Genomic and Phenotypic Characterization of Two Novel Enterobacter Phages With EDTA-Enhanced Antibiofilm Activity.

Multidrug-resistant members of the Enterobacter cloacae complex (ECC) are increasingly linked to difficult-to-treat infections and biofilm-mediated antimicrobial tolerance. Here, two lytic phages, vB_EhoIP_HHH and vB_EluM_RZH, displaying podovirus-like and myovirus-like morphology, respectively, were isolated from the River Chelt. HHH has a 39,582 bp genome (51.2% GC, 63 ORFs), while RZH has a 174,197 bp genome (39.4% GC, 314 ORFs), with neither genome carrying antimicrobial resistance, virulence or lysogeny-associated genes. VIRIDIC and VICTOR analyses placed HHH within Kayfunavirus and RZH within Karamvirus, supporting their classification as distinct species. Both phages demonstrated rapid adsorption, short latent periods and stability across physiological pH and temperature ranges. A phage cocktail targeting MDR ECC strain was evaluated with EDTA against established biofilms. Crystal violet assays showed the greatest biomass reduction at MOI 10 with 0.5-0.75 mM EDTA. Bliss independence analysis revealed localized synergy within this window but significant overall antagonism at higher EDTA concentrations. CFU enumeration confirmed greater activity against 24 h than 48 h biofilms. The optimized combination also reduced recoverable bacteria in a fibroblast infection model while maintaining low LDH release. These findings identify two novel lytic Enterobacter phages and support a narrow EDTA concentration window for enhanced phage-mediated antibiofilm activity.

Biofilms↗

PubMed2026

Lipid-mediated activation of BLT2 promotes membrane repair to prevent cell death.

Various pathogenic microorganisms produce toxins that create pores in cell membranes, causing cell damage and disrupting the host epithelial barrier. Recently, we reported that mice lacking the G protein-coupled receptor leukotriene B4 receptor 2 (BLT2), which is expressed in vascular endothelial and alveolar epithelial cells, are highly susceptible to pneumolysin (PLY), a pneumococci-generated toxin. Although we clarified the protective roles of BLT2 in vascular endothelial cells, those in alveolar epithelial cells have not been elucidated. Here, we report that lipid mediator 12-hydroxyheptadecatrienoic acid (12-HHT), which is produced by membrane-damaged epithelial cells, prevents cell death by promoting membrane repair through BLT2. BLT2 promoted the release of PLY-bound plasma membranes as extracellular vesicles in a sphingomyelinase-dependent manner. Additionally, BLT2 activated Rac1 and subsequent actin polymerization, leading to resistance to cell death. Furthermore, inhibition of 12-HHT production by aspirin and treatment with a BLT2 antagonist abolished the protective effect of BLT2. These findings provide a new therapeutic strategy for bacterial infection.

Receptors, Leukotriene B4↗

PubMed2026

Effectiveness and usability of artificial intelligence-powered assistive technologies in Supporting daily activities of children with cerebral palsy: a systematic review.

BACKGROUND: Cerebral Palsy (CP) is the main cause of motor disabilities in childhood, necessitating innovative approaches to rehabilitation and assistive technology (AT). Simultaneously, artificial intelligence (AI) is increasingly being integrated into devices to create more adaptive, personalized, and effective AT. This systematic review aimed to evaluate the effectiveness and usability of AI-powered assistive technologies designed to support daily activities and rehabilitation in children with CP. MATERIALS AND METHODS: Five databases, including Scopus, Web of Science, PubMed, Embase, and IEEE Xplore, were systematically searched, and 23 articles were included in the final analysis. Articles were identified, selected, and categorized into emerging thematic areas based on the primary function and application of the technology. RESULTS: Five key thematic topics were identified: 1) AI-driven motor rehabilitation and gait training for functional mobility; 2) intelligent assessment and monitoring systems for clinical decision support; 3) AI-supported communication, social interaction, and intention recognition tools; 4) gamified and virtual reality-based interventions to enhance engagement and usability; and 5) smart assistive systems supporting daily living and independent mobility. The findings demonstrate a strong trend toward the application of AI technologies in personalized, engaging, and data-driven interventions for children with CP. However, the field is predominantly in the proof-of-concept stage, with limitations including small sample sizes, lack of long-term clinical validation, challenges in user-centered design, and usability for children with CP. CONCLUSION: AI-powered assistive technologies hold significant potential for transforming the care of children with CP by enabling highly personalized and engaging interventions. To actualize this potential, future work must realize that practical application remains challenging owing to limited clinical validation, technological integration, and usability barriers for children with CP. Future research must prioritize user-centered design and multidisciplinary collaboration to ensure that AI and robotic advancements improve the usability and quality of life for children with CP.

Humans↗

PubMed2026

Gender-specific pathways linking body dissatisfaction, self-disgust, and social anxiety in Chinese adolescents: A three-wave longitudinal study.

Adolescence is a critical period for physical and psychological development. Body dissatisfaction is a significant concern during this stage, contributing to psychological issues such as social anxiety. However, the longitudinal relationships among body dissatisfaction, self-disgust, and social anxiety, as well as the potential role of gender differences in these dynamics, remain unclear. A total of 1109 junior high school students in China completed the baseline survey, with data collected at three time points (Mage = 12.67 years, SD = 0.68; 51.9% girls). Data were collected using the Body Areas Satisfaction Scale (BASS), the Self-Disgust Scale (SDS), and the Social Anxiety Scale for Children (SASC). Structural equation modeling (SEM) was employed to examine the longitudinal mediating effects among body dissatisfaction, self-disgust, and social anxiety, as well as to explore gender differences in these relationships. After controlling for autoregressive effects of self-disgust and social anxiety across waves, body dissatisfaction at T1 was found to indirectly predict social anxiety at T3 through self-disgust at T2, while indirectly predicting self-disgust at T3 through social anxiety at T2. Multi-group analyses revealed significant gender differences: for females, only the mediating pathway with self-disgust as the mediator was significant; for males, only the pathway with social anxiety as the mediator was significant. These findings contribute to a more nuanced understanding of the emotional mechanisms linking body dissatisfaction to social anxiety and highlight the importance of considering gender-specific pathways in prevention and intervention efforts.

Adolescent↗

PubMed2026

Intraspecific variation in Bothrops neuwiedi snake venom: Influence of age and sex.

Snake venom is a complex mixture of molecules and is subject to intraspecific variations due to the influence of abiotic and/or biotic factors, one of which is the animal's ontogeny. Some studies have already shown the influence of age on the composition and properties of snake venom, but these variations are not uniform, and each species may exhibit a specific pattern of variation. Therefore, this study aimed to analyze the influence of age on the venom of Bothrops neuwiedi, using 5 age groups, differentiating between males and females. To this end, we analyzed the protein profile of these venoms (using SDS-PAGE, HPLC, and proteomic analyses); enzymatic activities (PLA2, LAAO, and proteolytic activities); coagulant activity, in vivo assays (MDH; LD50 and ED50), and immunorecognition tests (Western blotting and ELISA). Protein profile analysis showed that males exhibited a gradual increase in SVMP and PLA2 concentrations. Both sexes showed a decrease in CTL concentration and a loss of PLA2 activity, which occurred more gradually in males. Proteolytic activity did not show clear ontogenetic differences, but both sexes showed activity peaks in the 2-year-old and senile groups, with females exhibiting higher proteolytic activity than males. Regarding LAAO activity, it increased in males and decreased in females. Although the LD50 did not show age-dependent differences, the venom from the 1-year-old group took longer to cause death in mice but showed a higher hemorrhagic activity than seniles. Furthermore, more antivenom was needed to neutralize the venom from the 1-year-old group than the venom from the senile group; despite this, immunorecognition tests did not show significant ontogenetic variations. In conclusion, the venom of the snake B. neuwiedi undergoes ontogenetic variations with certain sexual differences, showing some peculiarities that have not been found in ontogenetic analyses of other species of the same genus.

Animals↗

PubMed2026

Epigenetic drift and LINE-1 activation in aging brain: Implications for neurodegenerative disease.

Brain aging and age-associated neurological diseases, such as Alzheimer's Disease (AD), Parkinson's Disease (PD), and Amyotrophic Lateral Sclerosis (ALS), are largely attributed to epigenetic drift which is characterized by the gradual accumulation of alterations in neural cell methylation patterns over time. These methylation changes are particularly evident in transposable element (TE)-derived sequences such as Long interspersed element-1 (LINE-1) which comprises approximately 17% of the human genome. During aging, LINE-1 elements gradually lose their methylation, as well as the regulatory safeguard mechanisms that usually keep them inactive. This repression loss can lead to LINE-1 reactivation, contributing to harmful effects including genomic instability, neuroinflammation, and more. Together these findings indicate that impaired epigenetic maintenance, especially in repetitive genome regions, plays a key role in biological aging of neurons and glial cells. In this narrative review, we discuss the methylation dynamics and regulatory mechanisms of LINE-1 retrotransposons, their activation processes during aging, and contribution to age-associated neurological diseases. We also highlight the potential of targeting LINE-1 methylation to restore methylation homeostasis, epigenetic stability and delay brain aging.

Humans↗

PubMed2026

Symptom assessment and health-related quality of life in children with lower urinary tract dysfunction: A retrospective cross-sectional study.

INTRODUCTION: Lower urinary tract dysfunction (LUTD) significantly impacts children's health-related quality of life (HRQoL), but key determinants of this impairment remain incompletely understood within a patient-centered framework. METHODS: This retrospective cross-sectional study enrolled 272 children with LUTD. Clinical symptoms were assessed using the Dysfunctional Voiding Scoring System (DVSS) and the Overactive Bladder Symptom Score (OABSS), and HRQoL via the Pediatric Quality of Life Inventory (PedsQL™) 4.0 Generic Core Scales. RESULTS: The mean total PedsQL score was 83.66 ± 16.07, with the School Functioning domain being the most impaired (73.75 ± 20.94). Univariate analysis identified older age (≥11 years), daytime urinary leakage, overactive bladder (OAB) symptoms, and abnormal DVSS scores as factors associated with reduced HRQoL (all P < 0.05); multivariate regression further confirmed only older age and abnormal DVSS were independent influencing factors (both P < 0.001). A significant negative correlation existed between the total DVSS score and the total PedsQL score (r = -0.390, P < 0.01), indicating that greater symptom severity predicts poorer overall HRQoL. CONCLUSION: This study indicates that in children with LUTD, the severity of voiding dysfunction (quantified by DVSS) is inversely correlated with HRQoL. Voiding dysfunction impairs multiple domains of daily functioning, including physical well-being, emotional adjustment, social interaction, and school performance. Shifting from a symptom-focused to a patient-centered care model and integrating routine HRQoL assessment into standard clinical management can optimize clinical practice for pediatric LUTD.

Humans↗

PubMed2026

Single-cell transcriptome revealed the aberrant keratinocytes activation in antigen presentation in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD), a common chronic inflammatory skin disease, has been extensively studied using single-cell genomics. However, keratinocytes, as key effector cells in AD, have underlying mechanisms remain incompletely understood and require further investigation. METHODS: We integrated single-cell transcriptomic data from skin tissues of healthy controls, chronic active AD patients, spontaneously healed AD (SHAD) patients, and an ovalbumin-induced AD mouse model. The study particularly emphasized the gene expression and cellular dynamics of keratinocytes across the different groups, as well as their interactions with immune cells. RESULTS: Compared to healthy controls, we observed significant changes in the keratinocyte transcriptome, cellular state, and keratinocyte-immune cell ligand-receptor interactions in AD skin, particularly the marked activation of genes involved in antigen processing and presentation. Interestingly, such gene activation was not observed in keratinocytes from the ovalbumin-induced AD mouse model, despite its phenotype closely resembling human AD. Furthermore, in SHAD, we identified a recovery of both the ligand-receptor interaction patterns and antigen processing and presentation genes, accompanied by a notable shift in the transcriptome. This involved a significant downregulation of genes related to cytoplasmic transcription and oxidative phosphorylation. Notably, this pattern was not observed in the self-healing mouse model following the removal of ovalbumin stimulation. CONCLUSION: Our results suggest that the persistent activation of antigen processing and presentation pathways in keratinocytes may be a key driver of chronic inflammation in AD. Therefore, redirecting anti-allergic therapeutic strategies from solely targeting immune cells to targeting of keratinocyte-mediated antigen presentation may offer a more effective approach. Furthermore, we raise concerns about the use of ovalbumin-induced mouse models to recapitulate human chronic AD, as the underlying mechanisms may differ significantly.

Dermatitis, Atopic↗