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.

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.

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.

Probabilistic Integrated Human Mixture Risk Assessment of Multiple Metals Through Seafood Consumption.

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.

Anemia risk in relation to lead exposure in lead-related manufacturing.

BACKGROUND: Lead-exposed workers may suffer adverse health effects under the currently regulated blood lead (BPb) levels. However, a probabilistic assessment about lead exposure-associated anemia risk is lacking. The goal of this study was to examine the association between lead exposure and anemia risk among factory workers in Taiwan. METHODS: We first collated BPb and indicators of hematopoietic function data via health examination records that included 533 male and 218 female lead-exposed workers between 2012 and 2014. We used benchmark dose (BMD) modeling to estimate the critical effect doses for detection of abnormal indicators. A risk-based probabilistic model was used to characterize the potential hazard of lead poisoning for job-specific workers by hazard index (HI). We applied Bayesian decision analysis to determine whether BMD could be implicated as a suitable BPb standard. RESULTS: Our results indicated that HI for total lead-exposed workers was 0.78 (95% confidence interval: 0.50-1.26) with risk occurrence probability of 11.1%. The abnormal risk of anemia indicators for male and female workers could be reduced, respectively, by 67-77% and 86-95% by adopting the suggested BPb standards of 25 and 15 µg/dL. CONCLUSIONS: We conclude that cumulative exposure to lead in the workplace was significantly associated with anemia risk. This study suggests that current BPb standard needs to be better understood for the application of lead-exposed population protection in different scenarios to provide a novel standard for health management. Low-level lead exposure risk is an occupational and public health problem that should be paid more attention.

Assessing exposure risks for freshwater tilapia species posed by mercury and methylmercury.

Waterborne and dietborne exposures of freshwater fish to mercury (Hg) in the forms of inorganic (Hg(II)) and organic (methylmercury or MeHg) affect their growth, development, and reproduction. However, an integrated mechanistic risk model framework to predict the impact of Hg(II)/MeHg on freshwater fish is lacking. Here, we integrated biokinetic, physiological and biogeographic data to calibrate and then establish key risk indices-hazardous quotient and exceedance risk-for freshwater tilapia species across geographic ranges of several major rivers in Taiwan. We found that Hg(II) burden was highest in kidney followed by gill, intestine, liver, blood, and muscle. Our results showed that Hg was less likely to pose mortality risk (mortality rate less than 5 %) for freshwater tilapia species. However, Hg is likely to pose the potential hazard to aquatic environments constrained by safety levels for aquatic organisms. Sensitivity analysis showed that amount of Hg accumulated in tilapia was most influenced by sediment uptake rate. Our approach opens up new possibilities for predicting future fish population health with the impacts of continued Hg exposure to provide information on which fish are deemed safe for human consumption.

Quantifying the impact of drug combination regimens on TB treatment efficacy and multidrug resistance probability.

OBJECTIVES: TB patients' non-adherence to the multidrug treatment regimen is thought to be the main cause of the emergence of drug resistance. The purpose of this study was to quantify the impacts of two-drug combination regimens and non-adherence to these regimens on treatment efficacy and drug resistance probability. METHODS: A drug treatment modelling strategy was developed by incorporating a pharmacokinetic/pharmacodynamic model into a bacterial population dynamic model to explore the dynamics of TB bacilli and evolution of resistance during multidrug combination therapy, with an emphasis on non-adherence. A Hill-equation-based pharmacodynamic model was used to assess the bactericidal efficacy of single drugs and to estimate drug interactions. RESULTS: Non-adherence to the treatment regimen increased treatment duration by nearly 1.6- and 3.4-fold relative to compliance with treatment. Symptom-based intermittent treatment, a form of non-adherence, might lead to treatment failure and accelerated growth and evolution of resistant mutants, resulting in a dramatically higher probability of 4.17 × 10(-3) (95% CI 2.10 × 10(-4)-1.28 × 10(-2)) for the emergence of MDR TB. Overall, determination of the optimal treatment regimen depended on the different types of medication adherence. CONCLUSIONS: Our model not only predicts evolutionary dynamics, but also quantifies treatment efficacy. More broadly, our model provides a quantitative framework for improving treatment protocols and establishing an emergence threshold of resistance that can be used to prevent drug resistance.

[Investigation of spectroscopy of ZnCuInS/ZnSe/ZnS quantum dots].

ZnCuInS/ZnSe/ZnS quantum dots were non-toxic and heavy-metal free semiconductor nanocrystals. In the present paper, ZnCuInS/ZnSe/ZnS core/shell/shell quantum dots were prepared with the particle size of 3.3, 2.7 and 2.3 nm. The photoluminescence of ZnCuInS/ZnSe/ZnS quantum dots with different size were measured, and the wavelength of peak was blue-shifted with decreasing the diameter. The wavelength of absorption peaks and photoluminescence peaks were 510 nm, 611 nm (3.3 nm), 483 nm, 583 nm (2.7 nm) and 447 nm and 545 nm(2.3 nm). The obvious size-dependence of ZnCuInS/ZnSe/ZnS quantum dots was shown. The Stokes shifts of ZnCuInS/ZnSe/ZnS quantum dots were 398 meV (3.3 nm), 436 meV (2.7 nm) and 498 meV (2.3 nm). Such large Stokes shifts indicate that the emission should be ascribed to the defect-related recombination. The temperature-dependent photoluminescence of ZnCuInS/ZnSe/ZnS quantum dots with the particle size of 3.3 nm were measured. The wavelength of peaks was red-shifted with increasing temperature and the intensity of photoluminescence spectra was decreased with increasing temperature. Therefore, the emission was concluded to be the transition from the conduction band to defect state.

The Feasibility and Efficacy of Remote App-Guided Home Exercises for Frozen Shoulder: A Pilot Study.

Home exercise programs are beneficial in managing frozen shoulder (FS), yet adherence remains challenging. This pilot study introduces the remote app, Defrozen, designed for home exercises and assesses its feasibility and clinical outcomes in FS patients undergoing intra-articular and sub-acromial corticosteroid treatment. Over a four-week period, patients used the Defrozen-app, engaging in guided exercises. The feasibility of the intervention was assessed through several measurement scales, including adherence, the Technology Acceptance Model 2 (TAM2), the System Usability Scale (SUS), and User Satisfaction and Engagement (USE). Clinical outcomes included pain scale, Oxford Shoulder Score (OSS), Quick Disability of the Arm, Shoulder, and Hand (QuickDASH) Score, and passive range of motion. The TAM2 results indicated high perceived usefulness (4.5/5), ease of use (4.8/5), and intention to use (4.4/5); the SUS score was high at 81.7/100, complemented by USE scores reflecting ease of learning (4.9/5) and satisfaction (4.3/5). Clinical outcomes showed significant pain reduction, improved shoulder function, reduced shoulder-related disability, and increased shoulder range of motion. These findings suggest the Defrozen-app as a promising solution for FS, significantly improving adherence and showing potential to enhance clinical outcomes. However, these clinical outcome results are preliminary and necessitate further validation through a large-scale randomized controlled trial to definitively confirm efficacy and assess long-term benefits.

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.

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.

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.

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.

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.

[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.

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.

Stress-induced phosphoprotein 1 as a secreted biomarker for human ovarian cancer promotes cancer cell proliferation.

Ovarian cancers are frequently not diagnosed until advanced stages, resulting in a high case fatality rate. Because of this, more tumor markers, in addition to CA125, for detecting and monitoring ovarian cancer are needed. During a systematic search for potential biomarkers of ovarian cancer, we compared the protein profiles between tumor interstitial fluid and normal interstitial fluid of ovaries, rationalizing that abnormal levels of proteins in tumor interstitial fluid may be detected in peripheral blood and thus serve as easily accessible tumor markers. Here, we show that stress-induced phosphoprotein 1 (STIP1) was secreted by ovarian cancer tissues into the peripheral blood of patients, resulting in a significant increase of serum levels of STIP1 in cancer patients compared with those in age-matched normal controls. Our results further indicated that combined use of CA125 and STIP1 may increase early detection of ovarian cancer. Functionally, recombinant STIP1 significantly induced ERK phosphorylation, promoted DNA synthesis, and increased Ki-67 immunoreactivity in ovarian cancer cells, suggesting that STIP1 in vitro promotes cell proliferation. Colocalization of STIP1 and phospho-ERK in human ovarian cancer tissues also supports an in vivo activation of ERK by STIP1. Further understanding of molecular roles of STIP1 in human ovarian cancer may shed light on its pathophysiology and development of novel therapeutic strategies.

Assessing trends and predictors of tuberculosis in Taiwan.

BACKGROUND: Variety of environmental and individual factors can cause tuberculosis (TB) incidence change. The purpose of this study was to assess the characteristics of TB trends in the period 2004 - 2008 in Taiwan by month, year, gender, age, temperature, seasonality, and aborigines. METHODS: The generalized regression models were used to examine the potential predictors for the monthly TB incidence in regional and national scales. RESULTS: We found that (i) in Taiwan the average TB incidence was 68 per 100,000 population with mortality rate of 0.036 person-1 yr-1, (ii) the highest TB incidence rate was found in eastern Taiwan (116 per 100,000 population) with the largest proportion of TB relapse cases (8.17%), (iii) seasonality, aborigines, gender, and age had a consistent and dominant role in constructing TB incidence patterns in Taiwan, and (iv) gender, time trend, and 2-month lag maximum temperature showed strong association with TB trends in aboriginal subpopulations. CONCLUSIONS: The proposed Poisson regression model is capable of forecasting patterns of TB incidence at regional and national scales. This study suggested that assessment of TB trends in eastern Taiwan presents an important opportunity for understanding the time-series dynamics and control of TB infections, given that this is the typical host demography in regions where these infections remain major public health problems.

A probabilistic transmission and population dynamic model to assess tuberculosis infection risk.

The purpose of this study was to examine tuberculosis (TB) population dynamics and to assess potential infection risk in Taiwan. A well-established mathematical model of TB transmission built on previous models was adopted to study the potential impact of TB transmission. A probabilistic risk model was also developed to estimate site-specific risks of developing disease soon after recent primary infection, exogenous reinfection, or through endogenous reactivation (latently infected TB) among Taiwan regions. Here, we showed that the proportion of endogenous reactivation (53-67%) was larger than that of exogenous reinfection (32-47%). Our simulations showed that as epidemic reaches a steady state, age distribution of cases would finally shift toward older age groups dominated by latently infected TB cases as a result of endogenous reactivation. A comparison of age-weighted TB incidence data with our model simulation output with 95% credible intervals revealed that the predictions were in an apparent agreement with observed data. The median value of overall basic reproduction number (R0) in eastern Taiwan ranged from 1.65 to 1.72, whereas northern Taiwan had the lowest R0 estimate of 1.50. We found that total TB incidences in eastern Taiwan had 25-27% probabilities of total proportion of infected population exceeding 90%, whereas there were 36-66% probabilities having exceeded 20% of total proportion of infected population attributed to latently infected TB. We suggested that our Taiwan-based analysis can be extended to the context of developing countries, where TB remains a substantial cause of elderly morbidity and mortality.