10/05/2024


Aromatic antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs) add up to the limited use of the AEDs in the treatment and prevention of seizures. Human leukocyte antigen-B (HLA-B) alleles have been linked to AEDs-induced cADRs. We investigated the association between cADRs (including Stevens-Johnson syndrome; SJS/toxic epidermal necrolysis; TEN, drug reaction with eosinophilia and systemic symptoms; DRESS, and Maculopapular eruption; MPE) caused by AEDs (phenytoin, carbamazepine, lamotrigine, phenobarbital and oxcarbazepine) and HLA-B alleles in Thai population. Through the case-control study, 166 patients with AEDs-induced cADRs, 426 AEDs-tolerant patients (AEDs-tolerant controls), and 470 healthy subjects (Thai population) were collected. The HLA genotypes were detected using the polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. We also performed a meta-analysis with these data and other populations. The carrier rate of HLA-B*1502 was significantly diith the AEDs-tolerant group (p = 0.029, 0.007, and 0.017, respectively). The HLA-B*1502 allele may represent a risk factor for AEDs-induced cADRs.
Making landfall in Rockport, Texas in August 2017, Hurricane Harvey resulted in unprecedented flooding, displacing tens of thousands of people, and creating environmental hazards and exposures for many more.

We describe a collaborative project to establish the Texas Flood Registry to track the health and housing impacts of major flooding events.

Those who enroll in the registry answer retrospective questions regarding the impact of storms on their health and housing status. We recruit both those who did and did not flood during storm events to enable key comparisons. We leverage partnerships with multiple local health departments, community groups, and media outlets to recruit broadly. We performed a preliminary analysis using multivariable logistic regression and a binomial Bayesian conditional autoregressive (CAR) spatial model.

We find that those whose homes flooded, or who came into direct skin contact with flood water, are more likely to experience a series of self-reported health effects. Median household income is inversely related to adverse health effects, and spatial analysis provides important insights within the modeling approach.

Global climate change is likely to increase the number and intensity of rainfall events, resulting in additional health burdens. Population-level data on the health and housing impacts of major flooding events is imperative in preparing for our planet's future.
Global climate change is likely to increase the number and intensity of rainfall events, resulting in additional health burdens. Population-level data on the health and housing impacts of major flooding events is imperative in preparing for our planet's future.
As smoking prevalence has decreased in Canada, particularlyduring pregnancy and around children, and technological improvements have lowered detection limits, the use of traditional tobacco smoke biomarkers in infant populations requires re-evaluation.

We evaluated concentrations of urinary nicotine biomarkers, cotinine and trans-3'-hydroxycotinine (3HC), and questionnaire responses. We used machine learning and prediction modeling to understand sources of tobacco smoke exposure for infants from the CHILD Cohort Study.

Multivariable linear regression models, chosen through a combination of conceptual and data-driven strategies including random forest regression, assessed the ability of questionnaires to predict variation in urinary cotinine and 3HC concentrations of 2017 3-month-old infants.

Although only 2% of mothers reported smoking prior to and throughout their pregnancy, cotinine and 3HC were detected in 76 and 89% of the infants' urine (n = 2017). Questionnaire-based models explained 31 and 41% The pervasiveness of thirdhand smoke, the potential for dermal and oral routes of nicotine exposure, along with changes in public perceptions of smoking exposure and risk warrant further exploration.T cell exhaustion plays critical roles in tumor immune evasion. Novel strategies to suppress immune evasion are in urgent need. https://www.selleckchem.com/products/td139.html We aimed to identify potential compounds to target T cell exhaustion and increase response to immune checkpoint inhibitors (ICIs). Differentially expressed genes (DEGs) were identified between tumors with different immune evasion potential by comparing the transcriptome data. DEGs were then analyzed in the Connectivity Map (CMap) platform to identify potential compounds to increase response to ICIs. Gene set enrichment analysis, LDH release assay, Chromatin immunoprecipitation (ChIP), and Co-IP were performed to explore the potential mechanisms in vitro. Patients derived organoids and humanized xenograft mouse model were utilized to validate the finding ex vivo and in vivo. We identified 25 potential compounds that may play critical roles in regulating tumor immune evasion. We further pinpointed a specific compound, dexamethasone, which shows potent anti-tumor effect in multiple cancer cell lines when cocultured with T cells. Dexamethasone can suppress T cell exhaustion by decreasing the activity of two immune checkpoints simultaneously, including PD-L1 and IDO1. Functional study shows dexamethasone can increase the sensitivity of ICIs in coculture system, 3D organoid model and humanized mouse model. Mechanism study shows dexamethasone mediated transcriptional suppression of PD-L1 and IDO1 depends on the nuclear translocation of GR/STAT3 complex. These findings demonstrate dexamethasone can suppress immune evasion by inducing GR/STAT3 mediated downregulation of PD-L1 and IDO1 pathways.BACKGROUND Limited clinical data are available on bone loss in ankylosing spondylitis (AS) patients with hip involvement, especially for bone strength. The purpose of this study was to analyze bone strength and bone turnover markers in AS patients with hip involvement. MATERIAL AND METHODS The stiffness index (SI) calculated by quantitative ultrasound (QUS) was used to compare the bone strength between patients with AS with radiographic hip involvement (RHI-AS, BASRI-hip ≥2) and those without radiographic hip involvement (WORHI-AS, BASRI-hip ≤1). The Spearman correlation test was used to evaluate the association between SI and bone turnover markers [TP1NP, OC, ß-CTx, 25(OH)VD3, and PTH]. RESULTS RHI-AS (BASRI-hip ≥2) patients accounted for 52.2% (177/339) of all patients. There was no significant difference in most of the basic clinical features between RHI-AS and WORHI-AS patients, except for age and BMI. After adjusting for confounding factors (age and BMI), the stiffness index (SI) of RHI-AS patients was significantly lower than that of WORHI-AS patients (ORadj=0.