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The Wells-Riley model invokes human physiological and engineering parameters to successfully treat airborne transmission of infectious diseases. Applications of this model would have high potentiality on evaluating policy actions and interventions intended to improve public safety efforts on preventing the spread of COVID-19 in an enclosed space. Here, we constructed the interaction relationships among basic reproduction number (R

Idiopathic pulmonary fibrosis (IPF) is a fibrotic interstitial lung disease in which collagen progressively deposits in the supporting framework of the lungs. The pathological collagen creates a recalcitrant barrier in mesenchyme for drug penetration, thus greatly restricting the therapeutical efficacy. On the other hand, this overloaded collagen is gradually exposed to the bloodstream at fibrotic sites because of the vascular hyperpermeability, thus serving as a potential target. Herein, pathological collagen targeting and penetrating liposomes (DP-CC) were constructed to deliver anti-fibrotic dual drugs including pirfenidone (PFD) and dexamethasone (DEX) deep into injured alveoli. The liposomes were co-decorated with collagen binding peptide (CBP) and collagenase (COL). CBP could help vehicle recognize the pathological collagen and target the fibrotic lungs efficiently because of its high affinity to collagen, and COL assisted in breaking through the collagen barrier and delivering vehicle to the center of injured sites. Then, the released dual drugs developed a synergistic anti-fibrotic effect to repair the damaged epithelium and remodel the extracellular matrix (ECM), thus rebuilding the lung architecture. This study provides a promising strategy to deliver drugs deep into pathological collagen accumulated sites for the enhanced treatment of IPF.

Probiotics have been used to alleviate disease transmission in aquaculture. However, there are limited studies on probiotic use in modulating tilapia lake virus (TiLV). We assessed commercially available probiotic supplements used in TiLV-infected tilapia and performed mortality and cohabitation assays. We developed a mechanistic approach to predict dose-response interactions of probiotic effects on mortality and immune gene response. We used a susceptible-infected-mortality disease model to assess key epidemiological parameters such as transmission rate and basic reproduction number (R

To study the effect of orthodontic treatment with extraction on root resorption and alveolar bone morphology of the central incisor in adult patients.Eleven adult patients receiving orthodontic treatment were enrolled, and asked to take cone-beam CT(CBCT) scanning before and after treatment. Root resorption of the upper and lower central incisors after treatment, changes in alveolar bone thickness and height of alveolar bone were measured and compared. Statistical analysis was performed using SPSS 23.0 software package.The length of the tooth and root was reduced to a certain degree. The change in root length of the maxillary incisor was larger than that of the mandibular incisor. The alveolar bone width of the lingual and palatal neck of the central incisor showed some reduction, and alveolar bone width of the palatal neck of the upper central incisor and the middle lingual side of the mandibular central incisor changed to a certain extent. The width of the alveolar bone in the middle labial side of the mandibular central incisor increased, but the alveolar bone on the lingual and palatal side increased after orthodontic treatment, which was more obvious than that of the maxillary central incisor.Orthodontic treatment with tooth extraction is accompanied by a certain degree of root resorption of the central incisor and alveolar bone on the lingual and palatal side. However it is also accompanied by an increase in the amount of alveolar bone on the labial side. More fenestration and dehiscence are observed in the mandible.

A sharp increase in migrant workers has raised concerns for TB epidemics, yet optimal TB control strategies remain unclear in Taiwan regions. This study assessed intervention efforts on reducing tuberculosis (TB) infection among migrant workers. We performed large-scale data analyses and used them to develop a control-based migrant worker-associated susceptible–latently infected–infectious–recovered (SLTR) model. We used the SLTR model to assess potential intervention strategies such as social distancing, early screening, and directly observed treatment, short-course (DOTS) for TB transmission among migrant workers and locals in three major hotspot cities from 2018 to 2023. We showed that social distancing was the best single strategy, while the best dual measure was social distancing coupled with early screening. However, the effectiveness of the triple strategy was marginally (1–3%) better than that of the dual measure. Our study provides a mechanistic framework to facilitate understanding of TB transmission dynamics between locals and migrant workers and to recommend better prevention strategies in anticipation of achieving WHO’s milestones by the next decade. Our work has implications for migrant worker-associated TB infection prevention on a global scale and provides a knowledge base for exploring how outcomes can be best implemented by alternative control measure approaches.

Objectives To assess the potential epidemiological impact and cost-effectiveness of shorter antibiotic regimens in high tuberculosis (TB) burden regions of Taiwan. Methods This study combined the TB population dynamic model and cost-effectiveness analysis with local data to simulate the disease burdens, effectiveness and costs of hypothetical 4-month, 2-month and 7-day regimens compared with the standard regimen. Results The main outcomes were the potential of shorter regimens for averted incidence, mortality and disability-adjusted life years, incremental cost-effectiveness ratio and net monetary benefit. Shorter regimens would lower incidence rates and mortality cases in a high TB burden region by an average of 19–33% and 27–41%, respectively, with the potential for cost-effectiveness or cost-saving. The 2-month and 7-day regimens would be more cost-effective than the 4-month regimen. The threshold daily drug prices for achieving cost-effectiveness and cost-saving for 4-month, 2-month and 7-day regimens were $US1, $US2 and $US70, respectively. Such cost-effectiveness would remain, even if the willingness-to-pay threshold was less than one gross domestic product per capita. Conclusions The findings support the inclusion of shorter regimens in global guidelines and regional-scale TB control strategies, which would improve disease control, particularly in settings with high rates of incidence and poor treatment outcomes.

Background Exposure to ambient fine particulate matter (PM2.5) is associated with vascular diseases. Polycyclic aromatic hydrocarbons (PAHs) in PM2.5 are highly hazardous; however, the contribution of PM2.5-bound PAHs to PM2.5-associated vascular diseases remains unclear. The ToxCast high-throughput in vitro screening database indicates that some PM2.5-bound PAHs activate the aryl hydrocarbon receptor (AhR). The present study investigated whether the AhR pathway is involved in the mechanism of PM2.5-induced vascular toxicity, identified the PAH in PM2.5 that was the major contributor of AhR activation, and identified a biomarker for vascular toxicity of PM2.5-bound PAHs. Results Treatment of vascular smooth muscle cells (VMSCs) with an AhR antagonist inhibited the PM2.5-induced increase in the cell migration ability; NF-κB activity; and expression of cytochrome P450 1A1 (CYP1A1), 1B1 (CYP1B1), interleukin-6 (IL-6), and osteopontin (OPN). Most PM2.5-bound PAHs were extracted into the organic fraction, which drastically enhanced VSMC migration and increased mRNA levels of CYP1A1, CYP1B1, IL-6, and OPN. However, the inorganic fraction of PM2.5 moderately enhanced VSMC migration and only increased IL-6 mRNA levels. PM2.5 increased IL-6 secretion through NF-κB activation; however, PM2.5 and its organic extract increased OPN secretion in a CYP1B1-dependent manner. Inhibiting CYP1B1 activity and silencing OPN expression prevented the increase in VSMC migration ability caused by PM2.5 and its organic extract. The AhR activation potencies of seven PM2.5-bound PAHs, reported in the ToxCast database, were strongly correlated with their capabilities of enhancing the migration ability of VSMCs. Benzo(k)fluoranthene (BkF) contributed the most to the AhR agonistic activity of ambient PM2.5-bound PAHs. The association between PM2.5-induced vascular toxicity, AhR activity, and OPN secretion was further verified in mice; PM2.5-induced intimal hyperplasia in pulmonary small arteries and OPN secretion were alleviated in mice with low AhR affinity. Finally, urinary concentrations of 1-hydroxypyrene, a major PAH metabolite, were positively correlated with plasma OPN levels in healthy humans. Conclusions The present study offers in vitro, animal, and human evidences supporting the importance of AhR activation for PM2.5-induced vascular toxicities and that BkF was the major contributor of AhR activation. OPN is an AhR-dependent biomarker of PM2.5-induced vascular toxicity. The AhR activation potency may be applied in the risk assessment of vascular toxicity in PAH mixtures.

This study aimed to estimate the dietary risk of nitrates and nitrites in vegetables based on internal dose in a probabilistic manner by integrating exogenous exposure based on measured concentrations in vegetables with endogenous exposure using a toxicokinetic (TK) model. We optimized and validated a previous TK model and incorporated Monte Carlo simulations to account for variability across different age populations for predicting internal dose. High levels of nitrates were detected in leafy vegetables (from 545 ± 274 to 1641 ± 873 mg/kg). Nitrite contents of vegetables were generally low (from 1.26 ± 1.40 to 8.20 ± 14.1 mg/kg). The dietary risk was found to be different based on internal versus external dose, suggesting that it is critical to include endogenous nitrite formation into risk assessment. Nitrate and nitrite exposure from vegetables is unlikely to result in appreciable risks for most populations but may be a potential risk for preschoolers.

Background Broad-scale evidence has shown the significant association between ambient air pollutants and the development of tuberculosis (TB). However, the impact of air quality on the risk of TB in Taiwan is still poorly understood. Objective To develop a probabilistic integrated population-level risk assessment approach for evaluating the contribution of ambient air pollution exposure to the risk of TB development among different regions of Taiwan. Materials and methods A Bayesian-based probabilistic risk assessment model was implemented to link exposure concentrations of various air pollutants quantified in a probabilistic manner with the population-based exposure-response models developed by using an epidemiological investigation. Results The increment of the risk of TB occurred in a region with a higher level of air pollution, indicating a strong relationship between ambient air pollution exposures and TB incidences. Carbon monoxide (CO) exposure showed the highest population attributable fraction (PAF), followed by nitrogen oxides (NOX) and nitrogen dioxide (NO2) exposures. In a region with higher ambient air pollution, it is most likely (80% risk probability) that the contributions of CO exposure to development of TB were 1.6-12.2% (range of median PAFs), whereas NOX and NO2 exposures contributed 1.2-9.8% to developing TB. Conclusion Our findings provide strong empirical support for the hypothesis and observations from the literature that poor air quality is highly likely to link aetiologically to the risk of TB. Therefore, substantial reductions in CO, NOX, and NO2 exposures are predicted to have health benefits to susceptible and latently infected individuals that provide complementary mitigation efforts in reducing the burden of TB. Considering that people continue to be exposed to both TB bacilli and ambient air pollutants, our approach can be applied for different countries/regions to identify which air pollutants contribute to a higher risk of TB in order to develop potential mitigation programs.

The impacts of dietary nitrates and nitrites on human health have been a controversial topic for many years. However, the risk and benefit assessment of nitrates and nitrites is complicated by the large variation in nitrate and nitrite intake among people and the endogenous nitrite formation in the body. This study conducted a probabilistic risk–benefit assessment of dietary nitrates and nitrites based on internal dose by integrating exogenous and endogenous exposures with human trial data on cardiovascular benefits. A total diet study was carried out to quantify the age-specific dietary intakes of nitrates and nitrites. A previously well-validated human toxicokinetic model was used to predict internal doses for different age groups. In addition, the integrated approach was applied to different populations from different countries/regions based on reported exposure estimates to conduct a comprehensive risk–benefit assessment of dietary nitrates and nitrites. The results demonstrated that vegetable consumption was the main contributor to the internal nitrate and nitrite levels in all age groups. Exposure to nitrates and nitrites exceeding acceptable daily intakes in a variety of foods showed cardiovascular benefits. The probabilistic risk assessment showed that the exposure to nitrates and nitrites did not pose an appreciable health and safety risk. Therefore, the present results suggest that dietary nitrates and nitrites have clear cardiovascular benefits that may outweigh potential risks. Our analysis contributes significantly to addressing the controversy regarding risks and benefits from dietary nitrates and nitrites, and our approach could be applied to other dietary constituents with the potential for both risks and benefits.

Exposure to ambient volatile organic compounds (VOCs) is associated with a risk of cancer in the residents living near petrochemical facilities. However, research on the contribution of different VOCs to the lifetime cancer risk remains inconclusive. The variability in source emissions, geographical locations, seasons, and meteorological conditions can be assessed through long-term measurement of ambient VOCs with a wide spatial distribution, thus reducing the uncertainty of health risk assessment from source emissions. This study analyzed comprehensive measurement data of 109 VOCs at 17 monitoring stations around petrochemical industrial parks, collected once every six days during 2015-2018 by the Taiwan Environmental Protection Agency. We calculated the annual mean concentration of selected VOCs and then integrated the probability risk assessment (PRA) and positive matrix factorization (PMF) models to identify the sources of VOCs of high concern. First, we prioritized 12 out of 23 carcinogenic VOCs based on the PRA results. Further, the results obtained from the PMF model revealed that petrochemical industrial parks contributed to more than 50% of the emissions of six VOCs, namely 1,3-butadiene, benzene, 1,2-dichloroethane, chloroform, vinyl chloride, and acrylonitrile, measured at a few monitoring stations. This integrated approach can help regulatory agencies to efficiently propose control strategies on the emissions of VOCs of high concern, thereby reducing the population's health risk.

Chronic exposure to inorganic arsenic (iAs) is associated with chronic kidney disease (CKD) and urinary cancer, but the risks are poorly understood. Human biomonitoring can serve as a tool to better quantify human exposure and to conduct risk assessment. We aimed to assess the population risks of CKD and urinary cancer due to iAs intake based on the blood arsenic concentrations of 601 participants in Taiwan. A physiologically based pharmacokinetic modeling-based reverse dosimetry was conducted to estimate the daily intakes of iAs (DIiAs). We performed the benchmark dose (BMD) modeling for CKD using participants’ estimated glomerular filtration rate (eGFR) and the estimated DIiAs to derive a point of departure (POD). Margin of exposure (MOE) was used to characterize the risks. The population with eGFR values of

Combined risk assessment of endocrine effects of bisphenol A (BPA) and its analogues, such as bisphenols S, F, and AF (BPS, BPF, and BPAF), is challenging due to lack of related common toxicity metrics. This study conducted a population-based in vitro-to-in vivo extrapolation using physiologically based pharmacokinetic (PBPK) models coupled with Monte Carlo simulations to convert ToxCast in vitro estrogen receptor (ER) assays to human equivalent doses (HEDs). The ER pathway-based HEDs were compared with HEDs from animal studies and used to assess the combined risks for different populations across different countries/regions in a probabilistic manner. The estimated ER pathway-based HEDs for the four bisphenols (BPs) matched the animal-derived HEDs. The HEDs for the ER gene transcription (the common biological process target among BPs) were 0.40 (2.5th-97.5th percentiles: 0.06-5.42), 4.43 (0.69-53.84), 3.30 (0.51-626.57), and 1.12 (0.16-9.73) mg/kg/day for BPA, BPS, BPF, and BPAF, respectively. Results suggest a potentially moderate concern for combined risks of activating the ER pathway for toddlers and adults with high dietary exposures. This study presents in vitro-based credible HEDs for the four BPs and represents an advancement in the application of in vitro-in silico-based alternative approaches in human health risk assessment.

Inorganic arsenic (iAs), cadmium (Cd), lead (Pb), and methylmercury (MeHg) are toxic metals that cause substantial health concern and are present in various seafood items. This study linked probabilistic risk assessment to the interactive hazard index (HIINT ) approach to assess the human mixture risk posed by the dietary intake of iAs, Cd, Pb, and MeHg from seafood for different age populations, and joint toxic actions and toxic interactions among metals were also considered in the assessment. We found that, in combination, an iAs-Cd-Pb-MeHg mixture synergistically causes neurological toxicity. Furthermore, an iAs-Cd-Pb mixture antagonistically causes renal and hematological effects and additively causes cardiovascular effect. Our results demonstrated that if toxic interactions are not considered, the health risk may be overestimated or underestimated. The 50th percentile HIINT estimates in all age populations for neurological, renal, cardiovascular, and hematological effects were lower than 1; however, the 97.5th percentile HIINT estimates might exceed 1. In particular, toddlers and preschoolers had the highest neurological risk, with 0.16 and 0.19 probabilities, respectively, of neurological HIINT exceeding 1. Saltwater fish consumption was the principal contributor to the health risk. We suggest that regular monitoring of metal levels in seafood, more precise dietary surveys, further toxicological data, and risk-benefit analysis of seafood consumption are warranted to improve the accuracy of human mixture risk assessment and determine optimal consumption.

Yi-Hsien Cheng,1 Yi-Jun Lin,2 Szu-Chieh Chen,3,4 Shu-Han You,5 Wei-Yu Chen,6,7 Nan-Hung Hsieh,8 Ying-Fei Yang,9 Chung-Min Liao9 1Institute of Computational Comparative Medicine (ICCM), Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA; 2Institute of Food Safety and Health Risk Assessment, National Yang-Ming University, Taipei, Taiwan, Republic of China; 3Department of Public Health, Chung Shan Medical University, Taichung, Taiwan, Republic of China; 4Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan, Republic of China; 5Institute of Food Safety and Risk Management, National Taiwan Ocean University, Keelung, Taiwan, Republic of China; 6Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China; 7Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China; 8Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA; 9Department of Bioenvironmental Systems Engineering, National Taiwan University, Taipei, Taiwan, Republic of China Background: The high prevalence of dengue in Taiwan and the consecutive large dengue outbreaks in the period 2014–2015 suggest that current control interventions are suboptimal. Understanding the effect of control effort is crucial to inform future control strategies. Objectives: We developed a framework to measure season-based health burden risk from 2001 to 2014. We reconstructed various intervention coverage to assess the attributable effect of dengue infection control efforts. Materials and methods: A dengue–mosquito–human transmission dynamic was used to quantify the vector–host interactions and to estimate the disease epidemics. We used disability-adjusted life years (DALYs) to assess health burden risk. A temperature-basic reproduction number (R0)–DALYs relationship was constructed to examine the potential impacts of temperature on health burden. Finally, a health burden risk model linked a control measure model to evaluate the effect of dengue control interventions. Results: We showed that R0 and DALYs peaked at 25°C with estimates of 2.37 and 1387, respectively. Results indicated that most dengue cases occurred in fall with estimated DALYs of 323(267–379, 95% CI) at 50% risk probability. We found that repellent spray had by far the largest control effect with an effectiveness of ~71% in all seasons. Pesticide spray and container clean-up have both made important contributions to reducing prevalence/incidence. Repellent, pesticide spray, container clean-up together with Wolbachia infection suppress dengue outbreak by ~90%. Conclusion: Our presented modeling framework provides a useful tool to measure dengue health burden risk and to quantify the effect of dengue control on dengue infection prevalence and disease incidence in the southern region of Taiwan. Keywords: dengue, DALYs, modeling, infection, control intervention