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Definition and prevalence of residual disease in inflammatory arthritis: a systematic literature review and meta-analysis.

OBJECTIVE: To assess how residual disease (i.e., clinically relevant signs/symptoms despite achieving treatment targets) is defined in rheumatoid arthritis (RA), psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA), and estimate the prevalence/severity of residual disease in these diseases. METHODS: Systematic review of original research in RA/PsA/axSpA. Two key residual disease components were extracted: (1) the patient's disease state (often remission/low disease activity) and (2) which residual signs/symptoms were measured, e.g. swollen joints or fatigue (indicators of residual disease). Frequencies of the disease states and indicators were described (Objective 1). Prevalence (%) and severity (absolute score on instrument, e.g. fatigue NRS) of residual disease was analysed by indicator, using random effects meta-analysis (&#x2265;4 studies) or descriptively (<4 studies) (Objective 2). RESULTS: Regarding residual disease definitions (59 studies), disease states were almost exclusively disease activity-based (>99%), but with much variation in specific instruments/thresholds. Across diseases, physician-reported (66%) and patient-reported (73%) indicators were used more often than laboratory indicators to define residual disease (46%). Especially peripheral joint counts, pain, physical function and CRP were frequently used (42-56% of studies). The prevalence of residual disease (84 studies) was notable. For example, 5-25% of RA and PsA patients in remission still had swollen joints, and up to one-third reported relevant pain or fatigue. For axSpA, evidence was limited. CONCLUSION: Residual disease definitions in RA/PsA/axSpA are based on various disease activity instruments/thresholds and indicators (signs/symptoms). Residual disease affects up to half of patients. Future research should aim for a consensus-based definition of residual disease.

Humans

Integration of single-cell transcriptomics and genomic mutation analysis identifies an immunotherapy-resistant tumor subcluster and validates ARNTL2 as a malignant driver in lung adenocarcinoma.

BACKGROUND: Immunotherapy resistance in lung adenocarcinoma (LUAD) remains a critical clinical challenge, and the mechanisms underlying resistance-associated intratumoral heterogeneity are poorly characterized. METHODS: We performed single-cell RNA sequencing of LUAD patients receiving neoadjuvant immunotherapy (responders vs. non-responders), integrating inferCNV, GSVA, and differential expression analyses. Cluster-specific genes were validated across seven independent cohorts (TCGA-LUAD, GSE13213, GSE26939, GSE29016, GSE30219, GSE31210, GSE42127). A multi-algorithm machine learning framework was used to construct a prognostic model, and the immune microenvironment was characterized using TCIA scoring, seven infiltration algorithms, and ESTIMATE. ARNTL2 function was assessed by CCK-8 and Transwell assays in A549 and H1299 cells. RESULTS: Non-responders showed significant enrichment of epithelial cells, depletion of cytotoxic T/NK cells, and elevated copy number variation burden versus responders (p < 0.0001). A resistance-enriched malignant subcluster (Cluster 2) exhibited hyperproliferative and metabolic reprogramming signatures with upregulated KRT17, S100A2, and CST6, which showed tumor-specific overexpression, adverse prognostic value, and genomic amplification across cohorts. CoxBoost combined with survivalSVM achieved optimal predictive performance (C-index = 0.686), yielding robust risk stratification (HR: 2.54-10.51, all p < 0.05). Low-risk patients showed greater immune infiltration and higher TCIA immunophenoscores. ARNTL2 was an independent prognostic factor (HR: 2.07-4.64) strongly correlated with risk score (r = 0.69), and its knockdown suppressed proliferation and invasion in both LUAD cell lines (all p < 0.05). CONCLUSION: This study identifies a resistance-associated malignant subcluster in LUAD, constructs a validated CoxBoost + survivalSVM prognostic model with robust immune stratification, and establishes ARNTL2 as a core oncogenic driver and therapeutic target.

ARNTL2

Stable chloroform emissions in southeastern China: insights from recent observations.

Chloroform (CHCl3) is a short-lived ozone-depleting substance not currently regulated under the Montreal Protocol. Due to the unique meteorological conditions in East Asia, CHCl3 emitted in this region has a greater potential to reach the stratosphere and contribute to ozone depletion. As an essential component of national CHCl3 emissions, southeastern China has attracted increasing attention. However, long-term observational data in this region remain relatively scarce, with no updates since 2020. In this study, we continuously measured atmospheric CHCl3 concentrations at a remote monitoring station in southeastern China from 1 June 2023 to 31 May 2025. Frequent concentration enhancements were observed during the monitoring period, with mixing ratios ranging from 9.3 to 134.1 ppt and an average value of 36.8 &#xb1; 19.7 ppt. Back-trajectory analysis indicated that air masses associated with elevated CHCl3 levels primarily originated from coastal industrial provinces in eastern China. Using the Potential Source Contribution Function and Concentration Weighted Trajectory methods, we identified the Yangtze River Delta (Jiangsu, Anhui, and Zhejiang Provinces) and Jiangxi Province as dominant source regions. Emissions of CHCl3 in southeastern China were estimated using the Tracer Ratio Method to be approximately 30.1 &#xb1; 5.3 Gg/yr from 2023-06-01 to 2025-05-31, indicating overall stability relative to earlier estimates and no apparent upward trend. These findings provide updated insights into the current status of CHCl3 emissions in southeastern China and highlight the need for continued monitoring and emission assessment of CHCl3 in East Asia, given its unregulated status and implications for ozone layer recovery.

Air Pollutants

Medication safety in older adults in India: an integrative PhD synthesis of direct evidence and contextual implementation evidence.

BACKGROUND: Unsafe medication practices among older adults are an important global health concern, particularly in low- and middle-income countries where multimorbidity, fragmented care, self-medication, and informal healthcare provision intersect. OBJECTIVE(S): To synthesize direct evidence on medication safety among older adults in India and contextual evidence on deprescribing and community-level provider interventions relevant to safer medication use. METHODS: This PhD synthesis integrates four studies: a record-based cross-sectional study on polypharmacy and cardiovascular autonomic function in Kolkata; a six-city community study of 600 Indian older adults; a systematic review and meta-analysis on deprescribing preventive medications in frail or end-of-life older adults; and a systematic review of informal healthcare provider interventions in low- and middle-income countries. Studies I-II provided direct Indian older-adult evidence, while Studies III-IV provided indirect contextual evidence for their optimization and implementation. RESULTS: Polypharmacy was associated with higher anticholinergic burden and numerically higher cardiac autonomic neuropathy although residual confounding limits causal interpretation. In the multicity study, one-third had polypharmacy, while potentially inappropriate medications, prescribing omissions, and self-medication were common. Risks were higher with multimorbidity, recent hospitalization, care transitions, or living alone. Deprescribing showed no statistically significant increase in mortality, hospitalization, or major cardiovascular events, but heterogeneity was high and certainty low to very low. Informal-provider interventions showed the potential to improve knowledge, referral, case management, and medication-related practices. CONCLUSIONS: Medication safety among older adults in India requires an integrated continuum approach, but direct evidence supports only some components and implementation strategies that need prospective evaluation.

Humans

Boosting domestic wastewater treatment with quorum signal-augmented heterotrophic nitrification-aerobic denitrification bacterial-algal aerobic granular sludge.

The aerobic bacterial-algal granular sludge (ABGS) enhanced with heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria, as a novel symbiotic technology, exhibits fluctuating treatment efficiency and unstable performance primarily due to the unstable symbiotic relationship. This study proposes an innovative approach to strengthening the bacteria-algae symbiosis by introducing exogenous signaling molecules. Concurrently, high-throughput, correlation analysis of environmental factors and metagenomic sequencing techniques are employed to elucidate the enhancement mechanisms of the signaling molecules. The results demonstrate that signaling molecule enhancement boosted total nitrogen (TN) removal efficiency by 24.51 % in the bacteria-algae symbiotic system (X1). Scanning electron microscopy (SEM) characterization revealed that the addition of signaling molecules resulted in more compact aerobic granular sludge (AGS) and markedly improved stability. High-throughput sequencing showed signaling molecules enriched denitrifying bacteria (Hydrogenophaga, Pseudoxanthomonas, Thauera, Zoogloea) and organic-degrading Desulfomicrobium, optimizing microbial diversity and enhancing nitrogen/organic removal. Correlation analysis of environmental factors indicate that the addition of C8-HSL facilitates the enrichment and functional activation of specific genera. Metagenomic analysis revealed that signaling molecules enhanced the system's denitrification performance by modulating gene expression and associated metabolic pathways. Quantitative polymerase chain reaction (qPCR) analysis further confirmed that the signaling molecules upregulated the expression of the napA, nirK, and nirS genes. An increased abundance of the napA gene facilitated aerobic denitrification (NO&#x2083;&#x207b;-N&#x2192;NO&#x2082;&#x207b;-N), while upregulated abundance of the nirK and nirS genes accelerated nitrite reduction (NO&#x2082;&#x207b;-N&#x2192;N&#x2082;). This study aims to provide theoretical and practical foundations for implementing advanced bacteria-algae symbiotic technologies.

Denitrification

Mapping the Molecular Evolution and Role of Wild Rice GLYIII Protein-Encoding Genes in Abiotic Stress Response.

To address the need for sustainable food production amid rapid global climate change, developing rice varieties that grow optimally even under harsh conditions is essential. An effective approach in this direction would be to harness the stress resilience traits of the crop wild relatives (CWRs) of rice. Among the various crucial stress-responsive genes, the Glyoxalase III (GLYIII) gene family is of utmost importance for its ability to detoxify the toxic glycolytic byproduct, methylglyoxal (MG), in a less energy-intensive, single-step process, as well as for its multifaceted cytoprotective role. In our study, a comprehensive genome-wide search across the Oryza genus revealed that GLYIII genes are conserved across wild rice genotypes. Their number has expanded during domestication, driven by gene duplications. Interestingly, only a few orthologous pairs showed positive selection, suggesting that the functions of most others need to be constrained and or conserved.We found that higher GLYIII activity, Total Antioxidant Capacity, endogenous glutathione (GSH) levels, and free radical scavenging activity contributes to the stress resilience of wild rices O. punctata, O. meridionalis, and O. nivara, in addition to other factors. , , . , . Our qRT-PCR analysis revealed differential expression of the OpGLYIII, OmGLYIII, and OnGLYIII genes across different developmental stages and in response to various abiotic stresses. Furthermore, we report that wild rice GLYIII proteins, specifically OpGLYIII-3, OmGLYIII-3, and OnGLYIII-5, exhibit high catalytic efficiency over a broad pH range and at higher temperatures under in vitro assay conditions. Overexpression of these proteins was found to impart substantial stress resilience to the transformed E. coli cells. These findings collectively suggest that GLYIII proteins constitute a key component of the abiotic stress response machinery in wild rice.

Oryza

A stent-plus-irrigation protocol after adolescent hypospadias repair: a multicentre randomised controlled trial.

OBJECTIVES: To evaluate whether a stent-plus-irrigation protocol reduces complication rates following hypospadias repair in adolescents compared with catheter drainage alone. PATIENTS AND METHODS: In this multicentre randomised controlled trial, adolescents (Tanner Stage II-V) undergoing hypospadias repair were randomly assigned to either a stent-plus-irrigation group or a catheter-drainage group. The catheter-drainage group received standard urethral catheter drainage alone, whereas the stent-plus-irrigation group received an additional small-calibre urethral stent positioned within the reconstructed urethra and twice-daily saline irrigation. The primary outcome was the overall postoperative complication rate; secondary outcomes included urinary function and cosmetic outcomes. RESULTS: A total of 172 adolescents were assessed for eligibility, with 150 participants (75 in the stent-plus-irrigation group and 75 in the catheter-drainage group) included in the final analysis. Compared with the catheter-drainage group, the stent-plus-irrigation group demonstrated a significantly lower overall complication rate (risk ratio [RR] 0.33, 95% confidence interval [CI] 0.20-0.56; P&#x2009;<&#x2009;0.001), urethral fistula rate (RR 0.27, 95% CI 0.14-0.51; P&#x2009;<&#x2009;0.001), and surgical site infection (SSI) rate (RR 0.43, 95% CI 0.21-0.87; P&#x2009;=&#x2009;0.020). CONCLUSIONS: A postoperative stent-plus-irrigation protocol was associated with lower rates of postoperative complications, particularly urethral fistula and SSI, compared with catheter drainage alone after adolescent hypospadias repair. Because the intervention included both an additional urethral stent and saline irrigation, the independent contribution of irrigation cannot be determined in this two-arm trial.

Humans

Genomic characterization of a hypervirulent Aeromonas veronii NN0115 from Nile tilapia and head kidney transcriptome of infected fish reveals B-cell-dominated immune response with specific immunoglobulin downregulation.

Aeromonas veronii is a pathogen of multiple fish species, yet systematic understanding of its infection in Nile tilapia (Oreochromis niloticus) remains limited. A dominant strain, NN0115, was isolated from a natural outbreak and identified as A. veronii by 16S rRNA and whole-genome average nucleotide identity (ANI, 96.33%). Experimental infection revealed high virulence (LD50&#x202f;=&#x202f;3.41&#x202f;&#xd7;&#x202f;106&#x202f;CFU/mL, equivalent to 8.53&#x202f;&#xd7;&#x202f;104&#x202f;CFU/fish). The genome is 4.58&#x202f;Mb (58.57% GC) and encodes 4216 proteins. Virulence factor analysis identified 1253 genes, dominated by motility-related (264) and immune modulation (208) factors. Genomic island GI2 harbors 7 virulence genes and two dual-function resistance-virulence genes. The strain is resistant to 9 of 25 agents tested but carries three RND efflux pump genes whose predicted resistance was not phenotypically observed. The head kidney transcriptome of tilapia at 24&#x202f;h post-bacterial infection identified 773 differentially expressed genes; among them, 57 were immunoglobulin (Ig) genes, and 56 were down-regulated. Integration of published single-cell transcriptomic data showed that non-Ig B-cell marker genes were down-regulated by 32%, whereas Ig genes were reduced by 63%, indicating selective transcriptional suppression of Ig genes rather than a general decrease in B-cell transcriptional activity. Together, this study provides a comprehensive characterization of a highly virulent A. veronii from Nile tilapia and reveals that selective downregulation of B-cell Ig genes is the dominant transcriptional feature of the host head kidney response.

Animals

Six weeks of isometric resistance training led to evidence of corticospinal but not reticulospinal adaptation in previously untrained adult males.

The latest hypothesis regarding the source of enhanced neural activation from resistance training is the reticulospinal rather than the corticospinal tract, based on invasive animal and emerging human data. The present study employed a six-week isometric resistance training intervention in a randomized controlled design to address this knowledge gap. Thirty-nine healthy, untrained males (age ~23 y, sustained contraction group n = 13, explosive contraction group n = 9, control group n = 17) underwent neuromuscular and electrophysiological testing and completed all study requirements. Maximal isometric torque (MVC) and rate of torque development (RTD) were measured during a familiarization session as well as before and after the six-week period. Transcranial magnetic stimulation was used to assess motor-evoked potential (MEP) area and silent period duration while subjects contracted to 10% of MVC. Loud sound (120&#xa0;dB) was used to modulate MEP area and reaction time to visual stimuli during the StartReact test. Only the intervention groups demonstrated significant improvements in MVC (27%) and RTD (60%) (both P < 0.01), along with reduced MEP area (-&#xa0;21%) and silent period duration (-&#xa0;23%) (both P < 0.01). The sustained contraction group showed reduced modulation of reaction time and increased MEP suppression due to loud sound. Short-term resistance training seemed to reduce cortical inhibition and corticospinal excitability in both training groups. The study showed conflicting changes in measures purported to evaluate reticulospinal functioning. It is recommended to examine different forms of resistance training and longer training exposure in future.

Humans

Genomic determinants underlying biogenic amine detoxification phenotypes in food-associated lactic acid bacteria: Mechanism, evolutionary origin, and relevance to fermented food safety.

Biogenic amines (BAs) are toxic metabolites that accumulate in fermented foods and pose significant food safety concerns. Although several lactic acid bacteria (LAB) have previously been reported to exhibit strain-specific BA-degrading phenotypes, the genetic determinants underlying these activities have remained largely uncharacterized. Here, we analyzed 8251 LAB genomes to validate BA-degrading phenotypes. We predicted five BA-associated genes, including two direct biogenic amine-degrading genes (BADGs), mco and patA, and three polyamine-modifying genes (PMGs), speG, paiA, and bltD. Among BADGs, mco was broadly distributed across LAB and strongly enriched across food-associated niches. patA, organized within a conserved potD-glnB-potABC-patA cassette, is a putative, functionally distinct BADG in LAB, revealing a nitrogen-responsive polyamine uptake-catabolism module. Phylogenomics, phylogenetic reconciliation, and synteny analysis established that all five genes entered the LAB through episodic horizontal gene transfer followed by lineage-specific fixation. GC compositional bias and mobile genetic element association further corroborated the horizontal origin of the two BADGs. Structural analysis confirmed the conservation of catalytic core residues of BADGs across LAB, indicating strong purifying selection. Phenotype-to-genotype correlation with experimentally reported LAB suggested mco as a reliable genomic predictor of degrading phenotype. Integration of degradation and biosynthetic profiles predicted multiple LAB species capable of both synthesizing and degrading BA, along with 1823 genomes with degradation potential but lacking detectable BA biosynthesis genes. This study provides the first large-scale genome framework linking BA-degrading phenotypes with their genetic determinants in LAB and offers a rational basis for selecting BA-detoxifying strains for fermented food applications.

Biogenic Amines

Effects of Hydrogen-Rich Water Supplementation on Exercise Performance, Autonomic Nervous System Recovery, and Blood Lactate Concentration During Repeated Sprint Exercise in Male University Athletes.

Hydrogen-rich water (HRW) supplementation has been proposed to exert anti-fatigue effects during exercise; however, its impact on exercise performance and autonomic nervous system (ANS) function during repeated sprinting remains unclear. The aim of this study was to examine the effects of acute pre-exercise HRW ingestion on repeated sprint performance, ANS regulation, and blood lactate concentration. This randomized, single-blind, placebo-controlled crossover study included 13 male university athletes (23.9 &#xb1; 2.0 years). Each participant completed two sessions of 7&#xd7;6-second all-out cycling sprints interspersed with 30-second recovery intervals, with a one-week washout period between sessions. Critical flicker fusion frequency, heart rate, heart rate variability (HRV), and blood lactate were assessed at baseline, during exercise, and at 0-5 min and 10 min post-exercise. Compared to the placebo trial, the HRW trial demonstrated significantly higher average power output (d = 0.61) and significantly lower total work decrement and fatigue index (d = 0.62; d = 0.64). Post-exercise HRV recovery was significantly accelerated in the HRW trial, including RMSSD (d = 0.62), LF/HF ratio (d = 0.82), SampEn (d = 0.79), and DFA&#x3b1;1 (d = 0.79). Blood lactate at 3 min post-exercise was approximately 1 mmol/L lower in the HRW trial (d = 0.64). These findings suggest that acute HRW ingestion attenuates the decline in power output, accelerates ANS recovery, and enhances lactate clearance following repeated sprint exercise.

Humans

Plasma proteome profiling identifies XPNPEP3 as a novel biomarker associated with metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes mellitus.

OBJECTIVE: To identify plasma protein differences between type 2 diabetes mellitus (T2DM) patients with and without metabolic dysfunction-associated steatotic liver disease (MASLD), and to evaluate the diagnostic potential of X-prolyl aminopeptidase 3 (XPNPEP3) for identifying MASLD in T2DM patients. METHODS: Twenty T2DM inpatients were categorized into groups with and without MASLD and their plasma samples&#xa0;were analyzed using data-independent acquisition mass spectrometry, followed by bioinformatics analysis to identify differentially expressed proteins. The cohort was then expanded to 84 patients, and plasma XPNPEP3 levels were validated by enzyme-linked immunosorbent assay. Correlation between XPNPEP3 and clinical indicators were evaluated, and diagnostic performance was determined via receiver operating characteristic (ROC) analysis. Immunohistochemistry was employed to compare hepatic XPNPEP3 expression between the two groups. RESULTS: Proteomic analysis identified 176 differentially expressed proteins, with XPNPEP3 exhibiting the most significant down-regulation by fold change. In the validation cohort, plasma XPNPEP3 was significantly lower in T2DM+MASLD versus T2DM alone. XPNPEP3 levels were negatively correlated with diabetes duration, liver function markers, and triglyceride levels, and was identified as an independent factor inversely associated with MASLD in T2DM.ROC analysis demonstrated strong diagnostic performance for XPNPEP3, further enhanced when combined with BMI and diabetes duration.&#xa0; Immunohistochemistry confirmed reduced hepatic XPNPEP3 expression in T2DM+MASLD patients. CONCLUSIONS: Lower plasma XPNPEP3 is independently associated with MASLD in T2DM patients and demonstrates strong diagnostic potential, positioning XPNPEP3 as a promising biomarker for diagnosing MASLD in T2DM patients and a novel target for non-invasive diagnostic tool development.

Humans

An oxidative stress - and immunotherapy-related six-gene signature defines immune subtypes and predicts prognosis and immunotherapy response in hepatocellular carcinoma.

BACKGROUND: Oxidative stress and the tumor immune microenvironment jointly shape hepatocellular carcinoma (HCC) progression and response to immunotherapy, yet integrated biomarkers linking these processes are lacking. METHODS: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to identify oxidative stress- and immunotherapyrelated differentially expressed genes (OSIRDEGs). Functional enrichment, weighted gene co-expression network analysis (WGCNA) and LASSO-Cox regression were used to construct a prognostic signature. Consensus clustering, TIDE, CIBERSORT and ssGSEA characterized immune phenotypes. Somatic mutation, copy-number and drug-response data were integrated to assess genomic alterations and drug sensitivity. Expression of model genes was validated by qRT-PCR and western blotting in HCC cell lines. RESULTS: We identified 24 OSIRDEGs enriched in cell-cycle and mitotic pathways. WGCNA intersection yielded 18 module genes, from which a six-gene signature (BUB1B, CDKN2A, CENPE, HMMR, PTTG1, SPP1) was derived. The signature robustly stratified patients into high- and low-risk groups with significantly different progression-free and disease-free survival in both TCGA-LIHC and GSE14520. Based on signature expression, two molecular subtypes were defined, exhibiting distinct survival, immune landscapes and predicted immunotherapy responsiveness. Model genes harbored recurrent alterations and showed significant correlations with anticancer agents. All six genes were upregulated at mRNA and protein levels in metastatic HCC cell lines versus normal hepatocytes. CONCLUSIONS: We systematically explored the landscape of OSIRDEGs in HCC, and proposed a validated six-gene signature that refines prognostic stratification, delineates immunerelevant HCC subtypes and highlights candidate biomarkers for therapeutic selection and mechanistic investigation.

Humans

Occupationally relevant vibrations and the brain: frequency-dependent proteomics signatures in a rat model.

INTRODUCTION: Occupational exposure to whole-body vibration (WBV), particularly in agricultural environments, has been associated with adverse cognitive and physiological effects. This study examined the neurophysiological impact of WBV in a rat model at 4&#x202f;Hz and 30&#x202f;Hz, frequencies representative of off-road and on-road vehicle operation. METHODOLOGY: Forty-four Sprague-Dawley rats were assigned to control (0&#x202f;Hz), low-frequency (4&#x202f;Hz), or high-frequency (30&#x202f;Hz) vibration conditions. After three days of exposure, brain tissues were collected and analyzed using mass spectrometry-based proteomics to identify differentially expressed proteins. RESULTS: Proteomic profiling revealed distinct, frequency-dependent alterations in brain protein expression. Compared with controls, 32 cognition-related proteins were differentially regulated at 4&#x202f;Hz and 29 at 30&#x202f;Hz, with 13 differing between the two vibration conditions. Principal component analysis showed clear separation among groups, indicating unique proteomic signatures for each exposure frequency. Functional enrichment and protein-protein interaction analyses demonstrated involvement of synaptic plasticity, cytoskeletal organization, calcium regulation, and neurotransmitter release. Exposure to 4 Hz was associated with the upregulation of proteins involved in calcium homeostasis and synaptic integrity, suggesting potential disruption of cognitive processes. In contrast, 30 Hz increased the expression of proteins related to axonal guidance and neuroprotection, indicating a less clearly adverse response that may reflect adaptive or potentially beneficial effects. DISCUSSION: These findings provide new insight into biological mechanisms underlying WBV-induced cognitive changes and underscore the importance of vibration frequency in shaping neurophysiological outcomes. They also establish a foundation for future studies integrating proteomics with behavioural assessments in animals and humans.

Animals

A randomized study of antibiotic prophylaxis after hypospadias repair in children.

BACKGROUND AND OBJECTIVE: Antibiotic resistance is a challenge in contemporary world. Urethroplasty for hypospadias is one of the most common urological surgeries performed around the world, yet, there is still no consensus on the use of antibiotics pre- and post-operatively. Our objective was to analyze the effectiveness of antibiotic prophylaxis and therapy before, during, and after hypospadias repair in children. METHODS: A prospective randomized trial was carried out including patients with coronal hypospadias who underwent urethroplasty performed by one surgeon. Urethral catheters were used in all cases for 10 days. Study participants were randomly assigned in a 1:1:1 ratio to receive a single intraoperative administration of antibiotics (Group I); an intraoperative antibiotic prophylaxis and antibiotic therapy for 10 days until the removal of urethral catheter (Group II); no antibiotic administration (Group III). Randomization was performed using computer-generated permuted blocks with randomly varying block sizes, prepared by an independent statistician. The results were analyzed using the analysis of variance (ANOVA). The following criteria were compared: postoperative functional complications, such as: urethral fistula, stenosis, diverticulum; wound infection symptoms: hyperemia of surgical site, pain during palpation, and symptomatic urinary tract infection. RESULTS: A total of 300 patients were included in the study. Two patients (2%) in Group I, two patients (2%) in Group II, and four patients (4%) in Group III had urethral fistulas, requiring surgery 6 months after primary repair, yet without statistical difference between groups. We found no significant difference in frequency of symptomatic UTIs between three groups (p = 0.182). CONCLUSION: There is no effect of antibiotic prophylaxis and therapy on the frequency of postoperative surgical and infectious complications after urethroplasty for coronal hypospadias repair in children.

Humans

Nebivolol treatment improves hypertension-induced endothelial cell dysfunction by reducing TGF-&#x3b2;1-dependent senescence and normalizing mitochondrial indices.

OBJECTIVES: Serum from patients with hypertension (HT) causes endothelial cell (EC) damage, leading to senescence and dysfunctional phenotype. This study investigated whether serum from patients treated with the antihypertensive drugs could normalize EC activity. METHODS: This study involved 71 patients with newly diagnosed HT, who were randomly assigned to one of three groups based on the antihypertensive treatment: amlodipine, nebivolol, or perindopril. Serum samples collected before and 6&#x200a;weeks after treatment were applied to ECs in vitro to assess their angiogenic activity, cellular senescence, mitochondrial metabolism, and oxidative stress. RESULTS: Results showed that exposure of ECs to serum from patients treated for 6&#x200a;weeks significantly altered EC function, with varying effects among the drugs. Serum from nebivolol-treated patients produced the most consistent benefits, reducing EC proliferation and HIF-1&#x3b1; expression, likely due to lower levels of angiogenic factors such as angiopoietin-1, basic fibroblast growth factor (bFGF), insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF). Additionally, this serum contained reduced levels of pro-inflammatory cytokines (E-selectin, P-selectin, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor &#x3b1; (TNF&#x3b1;)) and lower TGF-&#x3b2;1, which are linked to HT-related EC senescence. Nebivolol treatment decreased senescence biomarkers such as SA-&#x3b2;-Gal, 53BP1, and p16, with SA-&#x3b2;-Gal reduction comparable to that of TGF-&#x3b2;1 neutralizing antibodies. Oxidative stress was reduced, indicated by lower oxidized DNA product levels. CONCLUSIONS: Nebivolol was the most effective at reducing the factors, associated with HT induced cellular senescence of endothelium, through reducing TGF-&#x3b2;1.

Humans

Faster N1 latency in response to homeostatic-like plasticity of PREPs is impaired during pain: A randomized-placebo capsaicin-pain study.

INTRODUCTION: Homeostatic-like plasticity (HP-like) stabilizes cortical excitability through long-term potentiation and depression-like mechanisms. The efficacy of homeostatic regulation in the corticomotor system is impaired during pain, which may have functional relevance for chronic pain. This study investigated whether a cortical HP-like response could be assessed by nociceptive stimulation, and if such response was impaired by experimental tonic pain. METHODS: Twenty-eight healthy participants completed placebo and capsaicin sessions, with 11 sham controls for time and design. HP-like plasticity was induced with two blocks of anodal tDCS over the primary motor cortex. The N1 (TP7) and N2P2 (Cz) components of electrically induced pain-related evoked potentials (PREPs) were assessed from the volar forearm before and after patch application, and again immediately and 20&#xa0;min after HP-like induction. An HP-like response was defined by PREP decrease after induction, and further normalization to baseline. RESULTS: Anodal tDCS did not induce an HP-like regulation of PREP amplitudes. Interestingly, an HP-like response was observed as a fastening of N1 latency after HP-like induction, which returned to baseline values after 20&#xa0;min. The latter effect was impaired during capsaicin-induced pain, where N1 was slower. The N2P2 component showed habituation over time in all sessions. CONCLUSION: This is the first study that investigates the HP-like regulation of nociceptive-evoked responses. An HP-like response was observed as a shortening of N1 latency, suggesting that early nociceptive processing may be susceptible to homeostatic regulation. In contrast, the later component, N2P2, showed habituation over time, which prevented evaluation of HP-like effects.

Humans

Multi-Omics Genome-Wide to Explore the Formation and Development Targets for Intracranial Aneurysms.

Intracranial aneurysms (IAs) represent a significant and potentially life-threatening category of disease, and there is currently a lack of effective treatment options aimed at preventing the progression of the disease. Accordingly, this study is dedicated to exploring and identifying effective drug targets that can help in the prevention of both the formation and rupture of IAs, along with a detailed examination of the underlying potential mechanisms involved in these processes. The data related to IAs for this research was obtained from the ISGC Biobank and UK Biobank. Then, we investigated the possible biological functions and unintended consequences of targeting the specific genes that were highlighted in IAs by using mediation analysis, virtual knockout experiments, and PW-MR studies. A total of 5 unique potential drug targets for IAs (FKTN, MAP3K1, PSMA4, SLC22A4, ADAM17), 4 unique potential drug targets for SAH (PSMA4, ADAM17, GPR160, SLC22A4), and 2 unique potential drug targets for UIA (SLC22A4, PRCP) were identified across brain or blood samples. Among the various candidates identified, SLC22A4 has emerged as a promising potential drug target, showing significant expression levels in both blood and brain tissues. Additionally, phenome-wide MR of SLC22A4 across 32 selected phenotypes did not identify statistically significant adverse associations after FDR correction. Virtual knockout (KO) experiments on SLC22A4 revealed that SLC22A4 KO disrupted 81 genes, all of which are involved in IAs-related pathways. Besides, we recognized BRD-K85337334 as potential candidates for targeting SLC22A4. This research indicates that an increase in SLC22A4 gene expression within the blood or brain is directly linked to a heightened risk of IAs rupture, which will aid in prioritizing the development of drugs for IAs.

Humans