Evaluation of Appropriate Conditions for Efficient Simultaneous Determination of US EPA and EU Priority Polycyclic Aromatic Hydrocarbons in Various Food Categories and Assessment of Their Consumption Risk.

The QuEChERS (quick, easy, cheap, effective, rugged and safe) conditions were optimized for efficient determination of the U.S. Environmental Protection Agency (US EPA) and European Union (EU) priority polycyclic aromatic hydrocarbons (PAHs) for the categories of grains, tuber & starchy vegetables, soy beans and products, fish & seafood, and poultry & meat, including raw materials and their corresponding products. The PAHs were analyzed using ultrahigh-performance liquid chromatography with temperature-controlled fluorescence detection and gas chromatography with tandem mass spectrometry. The established conditions had good accuracy, repeatability, and precision. Environmental pollution and processing methods influence the level of PAHs in samples. The low molecular weight PAHs were present in all raw materials, and processing increased high and low molecular weight PAHs in the products. The excess cancer risk for consumption of PAHs in cooked samples was mostly acceptable; a small number of samples might be of slight concern in certain age groups.

Worldwide serum concentration-based probabilistic mixture risk assessment of perfluoroalkyl substances among pregnant women, infants, and children.

Pregnant women, infants, and children are particularly vulnerable to perfluoroalkyl substances (PFASs), yet little is known about related health risks. Here, we aimed to study the four main PFASs: perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS), and assess the mixture risks of co-exposure to PFASs for pregnant women and children as well as for infants associated with maternal PFAS exposure at national and global scales, based on biomonitoring data on serum. We conducted a literature search and aggregated 69 data sources across 22 countries/regions from 2010 to 2020 to profile the serum concentrations of these four PFASs in pregnant women and children. Based on toxicity assessments by regulatory authorities, we determined conservative reference levels (RfLs) in the serum for the primary adverse effects of PFASs, including hepatic, developmental, and immune effects. The cumulative hazard quotient (HQ) was combined with probabilistic analysis to compare serum levels with RfLs and to quantify mixture risks. Our analysis revealed that PFOS was the dominant PFAS in maternal and child serum worldwide, with median levels 2.5-10 times higher than those of PFOA, PFNA, and PFHxS. The estimated global median serum levels of PFOS were 6.17 ng/mL for pregnant women and 4.85 ng/mL for children, and their immune effects in pregnant women and children are concerning as their cumulative HQs could exceed 1. For infants, the cumulative HQs for both developmental and immune effects could also be > 1, suggesting that maternal exposure to PFASs during pregnancy and breastfeeding may pose concerns for infant development and immunity. Our national and global serum database and risk assessment offer additional insights into PFAS exposures and mixture risks in susceptible populations, serving as a reference for evaluating the effectiveness of ongoing regulatory mitigation measures.

Assessing risk associated with recreational activities in coastal areas by using a bayesian network.

Taiwan is an island and therefore has a considerable amount of coastal land. Drowning or near-drowning incidents often occur in coastal recreational areas. To reduce the risk of drowning or near-drowning associated with marine recreational activities in Taiwan, this study collected data on the risk associated with marine recreational activities. It selected risk factors using a modified Delphi panel method, with an expert panel used to obtain probability values for each risk factor. A Bayesian network for risk assessment was then established. The results of this study can serve as a reference for stakeholders involved in marine recreational activities. Severe weather conditions increase wave height and current speed, resulting in an increased risk of drowning or near-drowning when coastal recreational activities occur under these conditions. Individuals who undertake marine recreational activities without safety awareness are more likely to exhibit risky behaviors. When self-rescue ability is insufficient to prevent possible danger, the probability of drowning or near-drowning is higher. Serious incidents may lead to death, and therefore, marine recreational activities should be avoided when weather conditions are poor. In addition, the safety awareness and self-rescue ability of individuals undertaking coastal recreational activities should be improved. This study did not explore emergency response measures or postincident policy management.

High-density lipoprotein regulates angiogenesis by long non-coding RNA HDRACA.

Normal high-density lipoprotein (nHDL) can induce angiogenesis in healthy individuals. However, HDL from patients with coronary artery disease undergoes various modifications, becomes dysfunctional (dHDL), and loses its ability to promote angiogenesis. Here, we identified a long non-coding RNA, HDRACA, that is involved in the regulation of angiogenesis by HDL. In this study, we showed that nHDL downregulates the expression of HDRACA in endothelial cells by activating WW domain-containing E3 ubiquitin protein ligase 2, which catalyzes the ubiquitination and subsequent degradation of its transcription factor, Kruppel-like factor 5, via sphingosine 1-phosphate (S1P) receptor 1. In contrast, dHDL with lower levels of S1P than nHDL were much less effective in decreasing the expression of HDRACA. HDRACA was able to bind to Ras-interacting protein 1 (RAIN) to hinder the interaction between RAIN and vigilin, which led to an increase in the binding between the vigilin protein and proliferating cell nuclear antigen (PCNA) mRNA, resulting in a decrease in the expression of PCNA and inhibition of angiogenesis. The expression of human HDRACA in a hindlimb ischemia mouse model inhibited the recovery of angiogenesis. Taken together, these findings suggest that HDRACA is involved in the HDL regulation of angiogenesis, which nHDL inhibits the expression of HDRACA to induce angiogenesis, and that dHDL is much less effective in inhibiting HDRACA expression, which provides an explanation for the decreased ability of dHDL to stimulate angiogenesis.

Large yellow croaker (Larimichthys crocea) mitofusin 2 inhibits type I IFN responses by degrading MAVS via enhanced K48-linked ubiquitination.

In mammals, mitofusin 2 (MFN2) is involved in mitochondrial fusion, and suppresses the virus-induced RIG-I-like receptor (RLR) signaling pathway. However, little is known about the function of MFN2 in non-mammalian species. In the present study, we cloned an MFN2 ortholog (LcMFN2) in large yellow croaker (Larimichthys crocea). Phylogenetic analysis showed that MFN2 emerged after the divergence of amphioxus and vertebrates. The protein sequences of MFN2 were well conserved from fish to mammals. LcMFN2 was expressed in all the tissues/organs examined at different levels, and its expression was upregulated in response to poly(I:C) stimulation. Overexpression of LcMFN2 inhibited MAVS-induced type I interferon (IFN) promoter activation and antiviral gene expression. In contrast, knockdown of endogenous LcMFN2 enhanced poly(I:C) induced production of type I IFNs. Additionally, LcMFN2 enhanced K48-linked polyubiquitination of MAVS, promoting its degradation. Also, overexpression of LcMFN2 impaired the cellular antiviral response, as evidenced by the increased expression of viral genes and more severe cytopathic effects (CPE) in cells infected with spring viremia of carp virus (SVCV). These results indicated that LcMFN2 inhibited type I IFN response by degrading MAVS, suggesting its negative regulatory role in cellular antiviral response. Therefore, our study sheds a new light on the regulatory mechanisms of the cellular antiviral response in teleosts. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00189-8.

Assessment of various conditions for the simultaneous determination of US EPA and EU priority PAHs in coffee samples and their PAHs consumption risk.

The optimal conditions for simultaneous determination of the U.S. Environmental Protection Agency (US EPA) and European Union (EU) priority polycyclic aromatic hydrocarbons (PAHs) in coffee beans and coffee brews were developed. The QuEChERS (quick, easy, cheap, effective, rugged and safe) technology combined with high performance liquid chromatography - temperature-controlled fluorescence detection and gas chromatography - tandem mass spectrometry were used in the investigation. PAHs could be determined in commercially available green coffee beans (possibly caused by environmental contamination), and their PAHs content increased with the degree of roasting. Coffee beans brewed with the coffee machine released more PAHs into their brews than those brewed with the drip bag. The PAHs consumption risk of the brewed coffee samples was not high due to their low PAH level. Nevertheless, the methods of roasting and brewing and the amount of drinking could still be considered to reduce the intake of PAHs.

Control measure implications of COVID-19 infection in healthcare facilities reconsidered from human physiological and engineering aspects.

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 (R0) - exposure time - indoor population number by using the Wells-Riley model to provide a robust means to assist in planning containment efforts. We quantified SARS-CoV-2 changes in a case study of two Wuhan (Fangcang and Renmin) hospitals. We conducted similar approach to develop control measures in various hospital functional units by taking all accountable factors. We showed that inhalation rates of individuals proved crucial for influencing the transmissibility of SARS-CoV-2, followed by air supply rate and exposure time. We suggest a minimum air change per hour (ACH) of 7 h-1 would be at least appropriate with current room volume requirements in healthcare buildings when indoor population number is < 10 and exposure time is < 1 h with one infector and low activity levels being considered. However, higher ACH (> 16 h-1) with optimal arranged-exposure time/people and high-efficiency air filters would be suggested if more infectors or higher activity levels are presented. Our models lay out a practical metric for evaluating the efficacy of control measures on COVID-19 infection in built environments. Our case studies further indicate that the Wells-Riley model provides a predictive and mechanistic basis for empirical COVID-19 impact reduction planning and gives a framework to treat highly transmissible but mechanically heterogeneous airborne SARS-CoV-2.

[Morphological changes of upper airway in patients with skeletal Class â ¢ malocclusion after bimaxillary surgery and correlation analysis].

PURPOSE: To analyze the morphological changes of the upper airway and related influencing factors in patients with skeletal Class Ⅲ malocclusion after bimaxillary surgery. METHODS: Twenty skeletal Class Ⅲ patients who underwent Le Fort I osteotomy and bilateral sagittal split ramus osteotomy(BSSRO) for maxillary advancement and mandibular setback were selected. The patients received CT scans before(T0) and 3-6 months after surgery, and the images were reconstructed three-dimensionally with Dolphin Imaging 11.9 software. Changes in the volume, cross-sectional area, and landmarks of each soft and hard tissue of the airway were measured. Statistical analysis of the data was performed using SPSS 25.0 software package. RESULTS: The volume of nasopharyngeal airway increased after operation (P＜0.05), and the volume of oropharyngeal airway decreased significantly(P＜0.01). The cross-sectional area of the airway at the plane of the second cervical vertebra was significantly decreased (P＜0.01), and the coronal and sagittal diameters were decreased(P＜0.05). The change of nasopharyngeal airway volume was moderately positively correlated with the sagittal change of the posterior nasal spine (r=0.460, P＜0.05), and the change of oropharynx and laryngopharyngeal airway volume was positively correlated with the vertical change of the midpoint of the soft palate(r=0.496, 0.696, P＜0.05). The airway cross-sectional area in the second and third cervical vertebra planes and the sagittal diameter of the airway in the third cervical vertebra plane were positively correlated with the vertical changes of the midpoint of the soft palate(r=0.474, 0.629, 0.547, P＜0.05). The change of airway cross-sectional area at the third cervical vertebra plane was moderately negatively correlated with the change of mandibular plane angle(r=-0.536, P＜0.05). CONCLUSIONS: The volume and cross-sectional area of oropharyngeal airway in skeletal Class Ⅲ patients after bimaxillary surgery will decrease. However, the total upper airway volume doesn't change significantly. The changes in the upper airway are correlated with the changes in some soft and hard tissue landmarks.

Pathological collagen targeting and penetrating liposomes for idiopathic pulmonary fibrosis therapy.

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.

[Cone-beam CT measurement of morphological changes of the root and alveolar bone of the central incisor during orthodontic treatment with extraction].

PURPOSE: To study the effect of orthodontic treatment with extraction on root resorption and alveolar bone morphology of the central incisor in adult patients. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Demographic Control Measure Implications of Tuberculosis Infection for Migrant Workers across Taiwan Regions.

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.

Aryl hydrocarbon receptor activation-mediated vascular toxicity of ambient fine particulate matter: contribution of polycyclic aromatic hydrocarbons and osteopontin as a biomarker.

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.

Assessing the effect of probiotics on tilapia lake virus-infected tilapia: Transmission and immune response.

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 (R0 ) based on our viral load dynamic data. We found that the most marked benefits of probiotics are significantly associated with immune system enhancements (~30%) and reductions in disease transmission (~80%) and R0 (~70%) in tilapia populations, resulting in a higher tolerance of farming densities (~400 fold) in aquaculture. These findings provide early insights as to how probiotic use-related factors may influence TiLV transmission and the immune responses in TiLV-infected tilapia. Our study facilitates understanding the mode of action of probiotics in disease containment and predicting better probiotic dosages in diet and supplements to achieve the optimal culturing conditions. Overall, our analysis assures that further study of rationally designed and targeted probiotics, or mechanistic modelling is warranted on the basis of promising early data of this approach.

An integrated strategy by using long-term monitoring data to identify volatile organic compounds of high concern near petrochemical industrial parks.

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.

Probabilistic risk and benefit assessment of nitrates and nitrites by integrating total diet study-based exogenous dietary exposure with endogenous nitrite formation using toxicokinetic modeling.

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.

Integration of biomonitoring data and reverse dosimetry modeling to assess population risks of arsenic-induced chronic kidney disease and urinary cancer.

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 <60 mL/min/1.73 m2 had significantly higher DIiAs (median: 3.20 µg/kg/day, 2.5th-97.5th percentiles: 2.35-4.67 µg/kg/day) than those with normal renal function (1.99, 1.22-3.42 µg/kg/day). The POD for CKD was 1.557 µg/kg/day, which could serve as a possible reference value for CKD risk assessment. The MOEs indicated that the CKD risk due to iAs intake may potentially be a cause for high concern for the population with reduced renal function. The iAs-induced urinary cancer risk may be a cause for moderate-to-high concern.

In vitro-in silico-based probabilistic risk assessment of combined exposure to bisphenol A and its analogues by integrating ToxCast high-throughput in vitro assays with in vitro to in vivo extrapolation (IVIVE) via physiologically based pharmacokinetic (PBPK) modeling.

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.

Shorter antibiotic regimens impact the control efforts in high tuberculosis burden regions of Taiwan.

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.

Assessing dietary exposure risk to neonicotinoid residues among preschool children in regions of Taiwan.

Neonicotinoids (NEOs) are a class of pesticides widely used worldwide. This study analyzed post-cooking residues of NEO pesticides and assessed their potential health risks for preschool children (0-6 years old) by conducting a total diet study (TDS). It involved food sampling, preparation, analysis of pesticide residues, estimation of food consumption data, and assessment of food safety risks. Food sampling was conducted between March and June 2015. A total of 128 food samples were obtained from 4 parts of Taiwan. After the food had been prepared, the 128 samples were aggregated into 32 composite food items and the NEO residues analyzed. Acetamiprid had the highest detection rate of the NEO residues (59.4%), and the concentrations ranged from not detected to 80.5 µg/kg. The estimated daily intake (EDI) of NEO residues among preschool children was found to be lower than the adjusted acceptable daily intake (ADI) even for highly exposed groups. The results showed that NEO pesticides were primarily detected in preserved fruits, cherry tomato, rape, bell fruit, and baby bok choy. The main health risk posed by detected NEO residues at high consumption rates for preschool children was attributed to acetamiprid (34.20 %ADI) and imidacloprid (23.69 %ADI), respectively. Therefore, this research implicates that the present level of NEO residues in the diets for preschool children in Taiwan does not exceed 100 %ADI.