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COVID-19 infection risk assessment in a kindergarten utilizing continuous air quality monitoring data
No full text[[abstract]]Researchers and transnational public health organizations have recognized aerosol transmission as an essential route of COVID-19 transmission. Therefore, improving ventilation systems is now adopted as a core preventive measure. As young children aged 2-6 in kindergartens generally lack vaccine protection and multiple infection clusters have been identified during the pandemic, we aimed to quantify the risk of aerosol transmission in kindergartens in Taipei, Taiwan. From August to November 2021, we conducted on-site visits and continuously monitored indoor air quality indicators including carbon dioxide (CO2) in a kindergarten located in northern Taiwan. We utilized the Wells-Riley model to estimate the basic reproduction number (R0) of each classroom and staff office, with input parameters including the number of occupants, duration of their stay, and indoor/outdoor CO2 concentration. Contagious settings were defined as those where the R0 estimate exceeded 1. We conducted a scenario/sensitivity analysis to assess the effect of simulated improvement measures. During school hours, the average concentration of CO2 in each classroom and the staff office was often more than 400 ppm higher than the outdoor levels. The R0 estimates gradually increased from Monday to Friday and throughout school hours, corresponding to the hourly and daily distribution of the CO2 concentration, which could not dissipate completely during off-duty time. The R0 estimates during school hours ranged from 3.01 to 3.12 in classrooms with a maximum of 30 occupants. To lower the R0 estimate, it is imperative to substantially reduce the number of occupants, the duration of their stay, and indoor CO2 concentration. The risk of outbreaks of cluster infections in kindergartens should not be underestimated. Feasible strategies to mitigate this risk should include improving ventilation systems through engineering control and limiting the number of indoor occupants and their time staying indoor through administrative control
Hormone therapy and venous thromboembolism risk in women of menopausal age: A target trial emulation
No full text[[abstract]]Contemporary data from randomized clinical trials focusing on the effect of oral hormone therapy (HT) on venous thromboembolism (VTE) in women aged 50-60 years are scarce despite evolving HT regimens. Here, we evaluated the association between HT and the risk of developing VTE using a target trial emulation among women of menopausal age. This retrospective cohort study applied a target trial emulation framework using claims data from a universal health insurance program in Taiwan. We emulated a sequence of trials in which women aged 50-60 years with no previous history of HT, hysterectomy, gynecologic disorders, or cardiovascular events were enrolled. Eligibility and HT use were evaluated monthly from 2011 to 2019. Eligible women were classified as either HT initiators or non-initiators for each consecutive month. Observational analogs of the intention-to-treat and per-protocol effects were estimated using pooled logistic regression models. Of the 150,686,148 eligible person-trials (3,001,112 women), 192,215 initiators and 768,860 propensity score-matched non-initiators were included in the analysis. The average duration of the HT was 1.25 years. Over a median follow-up of 5.83 years, 3,334 women developed VTE. The estimated hazard ratio (95% confidence interval) was 0.96 (0.88, 1.04) in the intention-to-treat analysis and 0.66 (0.41, 1.05) in per-protocol analysis. The estimated intention-to-treat and per-protocol 5-year VTE-free survival differences (95% confidence interval) were 0.1 parts per thousand (- 0.3 parts per thousand, 0.7 parts per thousand) and 0.3 parts per thousand (- 2.8 parts per thousand, 4.0 parts per thousand), respectively. In the contemporary clinical setting, we did not observe an increased VTE risk associated with HT in women aged 50-60 years
A self-cascading catalytic therapy and antigen capture scaffold-mediated t cells augments for postoperative brain immunotherapy
No full text[[abstract]]The recruitment of T lymphocytes holds great potential for suppressing the most aggressive glioblastoma (GBM) recurrence with immunotherapy. However, the phenomenon of immune privilege and the generally low immunogenicity of vaccines often reduce the presence of lymphocytes within brain tumors, especially in brain tumor recurrence clusters. In this study, an implantable self-cascading catalytic therapy and antigen capture scaffold (CAS) that can boost catalytic therapy efficiency at post-surgery brain tumor and capture the antigens via urethane-polyethylene glycol-polypropylene glycol (PU-EO-PO) segments are developed for postoperative brain immunotherapy. The CAS consists of 3D-printed elastomers modified with iron (Fe2+) metal-organic frameworks (MOFs, MIL88) and acts as a programmed peroxide mimic in cancer cells to initiate the Fenton reaction and sustain ROS production. With the assistance of chloroquine (CQ), autophagy is inhibited through lysosome deacidification, which interrupts the self-defense mechanism, further enhances cytotoxicity, and releases antigens. Then, CAS containing PU-EO-PO groups acts as an antigen depot to detain autologous tumor-associated antigens to dendritic cells maturation and T cell augments for sustained immune stimulation. CAS enhanced the immune response to postoperative brain tumors and improved survival through brain immunotherapy
Genetic variants in severe hypertriglyceridemia among taiwanese participants - insights from genome-wide association and whole-exome sequencing analyses
No full text[[abstract]]BACKGROUND: There are limited data on the use of whole-exome sequencing (WES) to diagnose severe hypertriglyceridemia. Our aim was to identify candidate genes linked to triglyceride levels via a genome-wide association study (GWAS) and to recruit participants with severe hypertriglyceridemia for WES to assess allelic variants in the candidate genes. METHODS AND RESULTS: A GWAS was conducted involving 120,140 participants to identify lead loci associated with blood triglyceride levels. Following the identification of these lead loci, WES was performed on DNA samples from 29 participants with hypertriglyceridemia whose triglyceride levels exceeded 800 mg/dL to assess variations in the corresponding genes. In the GWAS of 120,140 participants, the apolipoprotein A5 (APOA5) locus on chromosome 11 showed the strongest association with blood triglyceride levels (lead single nucleotide polymorphism [SNP] rs2075291; P=3.07×10(-108)), along with 5 independent SNPs (most significant P=7.84×10(-167)). Other key loci included BUD13 homolog (BUD13; P=2.73×10(-62)), glucokinase regulator (GCKR; P=2.63×10(-24)), and lipoprotein lipase (LPL; P=1.50×10(-11)). WES in 29 hypertriglyceridemia patients identified additional genes, including ALDH1A2, APOC1, LPL, RGS7, and SIK3, showing significant allele frequency variations and potential roles in lipid metabolism. CONCLUSIONS: Our study confirms the role of known genetic loci in triglyceride metabolism and hypertriglyceridemia while uncovering novel loci, offering new perspectives on lipid regulation and potential avenues for therapeutic advancements
Upper airway collapsibility during rapid eye movement sleep tracks the response to upper airway surgery for obstructive sleep apnea
No full text[[abstract]]OBJECTIVES: Endotype-based intervention has shown promise in treatment for patients with obstructive sleep apnea, and upper airway surgery is an important therapeutic option. However, the response to surgery varies among patients with obstructive sleep apnea. This study aims to examine changes in endotypic traits following upper airway surgery and their association with surgical outcome. METHODS: We prospectively recruited 25 patients with obstructive sleep apnea who visited a single sleep center for upper airway surgery and completed polysomnographic studies both before and following surgery. Endotypic traits during non-rapid eye movement and rapid eye movement sleep - including collapsibility (Vpassive), arousal threshold, loop gain, and upper airway compensation - were estimated using the Phenotyping Using Polysomnography method. Patients were classified as responders or non-responders based on improvements in the apnea-hypopnea index, and we compared pre-surgery endotypic traits between them using Mann-Whitney tests. Changes in pre- and post-surgery endotypic traits between responders and non-responders were compared using generalized linear mixed models. RESULTS: We identified 12 responders and 13 non-responders. Compared to non-responders, collapsibility during rapid eye movement sleep improved in responders (22.3 vs. - 8.2 %eupnea Vpassive, p = 0.01), and the arousal threshold decreased during non-rapid eye movement sleep in responders (-22.4 %eupnea, p = 0.02). No endotypic trait predicted surgical response, but AHI during rapid eye movement sleep was higher among responders than non-responders (51.8 vs. 34.4/h, p = 0.05). CONCLUSION: Upper airway surgery significantly reduced collapsibility during rapid eye movement sleep among responders. The target pathology for upper airway surgery is a compromised upper airway during rapid eye movement sleep
Prospective association of interventions for at-risk families with illicit drug use among young students in Taiwan
No full text[[abstract]]Background: Young people who use illicit drugs disproportionately experience multiple problems in individual, family, and school domains. With a focus on illicit drug-using middle schoolers, the present study aims to characterize intervention services for risk indicators and to examine the prospective associations with reinitiated use throughout adolescence. Methods: A retrospective cohort of 1605 adolescents was identified from the 2013 to 2016 national school-based indicated prevention program serving illicit drug-using students in Taiwan. Reinitiated use of illicit drugs was confirmed by the Drug Abuse Big Datasets comprising police arrest records. Information concerning the history of intervention services—attention deficit hyperactivity disorder (ADHD) treatment, intervention for at-risk families, and school dropout consultation—was ascertained from national administrative data. A cohort of young adolescents from the general population (n = 809,477) was sampled for comparison. The Cox proportional hazards model was used to evaluate the risk of drug use. Results: Nearly 80 % of illicit drug-involved middle schoolers used ketamine only, and 17 % used amphetamine or methamphetamine. Over a four-year follow-up, 35 % of middle schoolers were re-reported for drug use, with police arrest being the major source. A history of ADHD treatment was not linked with illicit drug use, whereas dropping out in early schooling can elevate middle schoolers’ hazard by 46 %. Notably, receiving services targeting at-risk families in late childhood can lower the hazard by 43 %, with the reduction even greater when non-school-attending adolescents were included. Discussion: To reduce progression into advanced drug involvement and substance use disorders, an integrated model of school-based interventions is urgently needed
Exposure distribution and profiles of paraben in Taiwanese (2013-2016)
No full text[[abstract]]Parabens are well-known endocrine disrupting chemicals (EDCs), which is added in food and pharmaceuticals and personal care products (PPCPs) as preservatives. Therefore, the aims of this study were: 1) to use the representative urine sample of the general Taiwan population and establish the background level of urinary parabens. We selected 1345 adults (ages 18-97 yrs) and 622 minors (ages 7-17 yrs) which was from a representative Survey from 2013 to 2016. The questionnaire, the morning blood sample and the first-morning urine sample were collected from the subjects and analyzed the urinary parabens from each participant including methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP) and butylparaben (BuP) by using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). We found the general Taiwanese were exposure at a high level of four parabens, especially MeP and PrP. The geometric mean (GM) of parabens for adults were higher than minors (adults: MeP, 395; EtP, 39.5; PrP, 103 and BuP 5.81 μg/L; minors: MeP, 288; EtP, 25.0; PrP, 65.4 and BuP 4.36 μg/L). The level of four parabens was higher than other countries. We concluded that paraben exposure of the general population in Taiwan varies by sex, age, and region. Exposure by the ≥18-year-old group to MeP, PrP, and BuP in Taiwan remains higher than that of adult from other countries. Reference values (RVs) of paraben in Taiwan were established in the current study
Recruitment for voluntary video and mobile HIV testing on social media platforms during the COVID-19 pandemic: Cross-sectional study
No full text[[abstract]]Background: The COVID-19 pandemic prompted social distancing policies and caused misinformation that hindered in-person HIV screening for high-risk groups. Social media platforms provide additional options for voluntary counseling and testing (VCT) for HIV, overcoming these limitations. However, there is a lack of data on HIV testing recruitment through social media platforms and its outcomes during the pandemic. Objective: This study aimed to measure the rate of face-to-face mobile and video VCT conducted after recruitment through social media platforms and friend referrals during the pandemic and compare the geographic distribution, risk feature targeting, testing outcome, and cost between the 2 models. Methods: Data were collected from March 3 to December 31, 2021, during the COVID-19 outbreak in Taiwan. Participants engaging in unprotected sex were recruited. After one-on-one message discussions through the platforms, the well-trained research assistants provided mobile or video VCT based on the participants’ availability. Primary outcomes were completion rate, testing results, and CD4 count. Secondary outcomes included demographic and HIV risk-taking and protective features from a questionnaire. Selection bias was controlled by adjusting for the testing site (Taipei vs non-Taipei) using univariable multinomial logistic regression. Results: This study gathered 5142 responses on the social media platforms, recruiting 1187 participants. Video VCT had a completion rate of 31.8% (207/651), higher than mobile VCT’s 21.8% (980/4491). Both rates were higher than those before the COVID-19 pandemic. Recruitment through friend referrals, instant messaging apps (eg, Line [LY Corporation]), and geosocial dating apps (eg, Hornet [Queer Networks Inc], Grindr [Grindr LLC], and Gsland [Tien-Hao Tsai]) resulted in higher acceptance and completion rates than social networks (eg, Facebook [Meta], X [formerly Twitter], and Instagram [Meta]). Mobile VCT had higher recruitment among urban residents and screening density, while video VCT reached a broader geographic area. The mobile group was more likely to have had more than 10 sexual partners (odds ratio [OR] 1.92, 95% CI 1.05-3.50; P=.03), history of sex work (OR 4.19, 95% CI 1.68-10.43; P=.002), and sexually transmitted diseases (OR 2.23, 95% CI 1.18-4.23; P=.01) within the past 3 months. The video group was more likely to meet sexual partners through social media. The HIV-positive rate in the mobile group was 0.7% (7/973) with an average CD4 count of 460/μL, while in the video group, it was 1% (2/205) with an average CD4 count of 347/μL, indicating a later diagnosis. Both positivity rates were higher than those before the COVID-19 pandemic, with no significant difference between the groups. The video group cost US 50.36 for the mobile group. Conclusions: Recruiting through social media platforms that facilitate one-on-one message discussions can effectively target high-risk groups for mobile and video VCT. This approach should be integrated into the current screening model to enhance HIV case finding
Fluvastatin, an HMG-CoA reductase inhibitor, exerts protective effect against NMDA-induced seizure by increasing the seizure threshold and modulating membrane excitability in embryonic rat cortical neuron
No full text[[abstract]]Background: Epilepsy affects nearly 50 million people worldwide. Previous studies have indicated the neuroprotective effects of statin on several neuropathological conditions. However, it is very much unknown whether fluvastatin was able to alter the seizure types related to neuronal excitability and progression mediated by NMDA receptor activation, and the mechanisms involved in these actions are not completely understood so far. Our study evaluated the effects of fluvastatin on the NMDA-induced seizure, BKCa channels activity, NMDA receptor activation opens BKCa current, sodium channel current, NMDA receptor-mediated current, and hyperexcitable neuronal activity associated with activation of NMDA receptor. Methods: The effects of fluvastatin on seizure thresholds induced by NMDA were monitored in mice. The cell-attached and whole-cell patch-clamp recordings were applied to evaluate the ionic currents and action potentials of rCN or SHSY5Y neuroblastoma cells. Results: The results of our study have demonstrated that fluvastatin did increase the NMDA-induced seizure threshold and suppressed the frequency of action potentials induced by NMDA. Notably, our findings provide the evidence that fluvastatin exhibits inhibitory effects on NMDA receptor-mediated current, BKCa channels currents, NMDA receptor activation opens BKCa current, and sodium channel currents in rCN and SHSY5Y neuroblastoma cells. Conclusion: Our findings suggested that fluvastatin may protect against seizure types related to neuronal excitability and NMDA receptor activation by inhibiting NMDA-mediated action potentials, NMDA receptor-mediated currents, BKCa channels, and sodium channels
Aminothiazole compounds as protein kinase inhibitors
No full text[[abstract]]Aminothiazole compounds of Formula (I) shown below and pharmaceutical compositions containing one of such compounds. Also disclosed are methods of inhibiting a tyrosine kinase and treating cancer associated with a tyrosine kinase with one of the aminothiazole compounds