The ligand binding domain of a type IV pilus chemoreceptor PilJ has a different fold from that of another PilJ-type receptor McpN.

Bacterial chemoreceptors sense the extracellular signals and regulate bacterial motilities, biofilm formation, etc. The periplasmic ligand binding domains of chemoreceptors occur as different structural folds and recognize a diversity of chemical molecules. In Pseudomonas aeruginosa (PAO1), two bacterial chemoreceptors, McpN (PA2788) and PilJ (PA0411), are proposed to both contain a PilJ-like ligand-binding domain (LBD) (Pfam motif PF13675) and involved in nitrate chemotaxis and type IV pilus-mediated motility, respectively. The LBDs of McpN and PilJ consist of 135 and 263 residues, respectively, and share very low sequence identity, suggesting they might occur as different structures. Here, we found that PilJ-LBD folded into an HBM module, the same as the sensor domains of McpS-LBD and TorS-LBD, but it differed from that of McpN-LBD. We also observed a trimer in SEC and AUC and proposed a trimeric model based on the crystal structure. Based on the sequence, we classified the Pfam containing McpN-LBD and PilJ-LBD into three classes: sPilJ (single PilJ) represented by McpN-LBD with only one PilJ domain, dPilJ (dual PilJ) that contained dual PilJ domains, and hPilJ (hybrid PilJ) that comprises of a PilJ domain and another non-PilJ domain. Our work indicates a significant structural difference between the ligand binding domains of PilJ and McpN and will help our further study on both kinds of chemoreceptors.

Clinical features, treatment, and follow-up of OPPG and high-bone-mass disorders: LRP5 is a key regulator of bone mass.

Osteoporosis-pseudoglioma syndrome (OPPG) and LRP5 high bone mass (LRP5-HBM) are two rare bone diseases with opposite clinical symptoms caused by loss-of-function and gain-of-function mutations in LRP5. Bisphosphonates are an effective treatment for OPPG patients. LRP5-HBM has a benign course, and age-related bone loss is found in one LRP5-HBM patient. PURPOSE: Low-density lipoprotein receptor-related protein 5 (LRP5) is involved in the canonical Wnt signaling pathway. The gain-of-function mutation leads to high bone mass (LRP5-HBM), while the loss-of-function mutation leads to osteoporosis-pseudoglioma syndrome (OPPG). In this study, the clinical manifestations, disease-causing mutations, treatment, and follow-up were summarized to improve the understanding of these two diseases. METHODS: Two OPPG patients and four LRP5-HBM patients were included in this study. The clinical characteristics, biochemical and radiological examinations, pathogenic mutations, and structural analysis were summarized. Furthermore, several patients were followed up to observe the treatment effect and disease progress. RESULTS: Congenital blindness, persistent bone pain, low bone mineral density (BMD), and multiple brittle fractures were the main clinical manifestations of OPPG. Complex heterozygous mutations were detected in two OPPG patients. The c.1455G > T mutation in exon 7 was first reported. During the follow-up, BMD of two patients was significantly improved after bisphosphonate treatment. On the contrary, typical clinical features of LRP5-HBM included extremely high BMD without fractures, torus palatinus and normal vision. X-ray showed diffuse osteosclerosis. Two heterozygous missense mutations were detected in four patients. In addition, age-related bone loss was found in one LRP5-HBM patient after 12-year of follow-up. CONCLUSION: This study deepened the understanding of the clinical characteristics, treatment, and follow-up of OPPG and LRP5-HBM; expanded the pathogenic gene spectrum of OPPG; and confirmed that bisphosphonates were effective for OPPG. Additionally, it was found that Ala242Thr mutation could not protect LRP5-HBM patients from age-related bone loss. This phenomenon deserves further study.

Development and validation of a scale to measure hypertensive Chinese individual's behavior toward salt reduction consumption.

OBJECTIVE: This study aimed to develop and validate the Salt Reduction Behavior Scale (SRBS) to measure the behavior of hypertensive Chinese individuals in adhering to salt reduction practices. METHODS: The SRBS was constructed based on the Health Belief Model, consisting of five constructs: knowledge, perceived severity, perceived benefits, perceived barriers, and cues to action. Data were collected from 2,082 hypertensive patients in Beijing, China, who completed a questionnaire administered through an online platform. Kaiser-Meyer-Olkin (KMO) test was used to assess the adequacy of the sample and the Bartlett's test of sphericity to examine the factorability of the dataset. Confirmatory Factor Analysis (CFA) was used to assess the structural validity and reliability of the SRBS. RESULTS: The KMO analysis yielded a notably elevated value of 0.95, indicating that the data was highly suitable for Exploratory Factor Analysis (EFA). Bartlett's test of sphericity yielded a statistically significant test statistic (P < 0.001). The 32-item SRB questionnaire demonstrated strong internal consistency with a Cronbach's alpha coefficient of 0.923. A second-order Confirmatory Factor Analysis (CFA) revealed that, after removing the unrelated construct of barriers, SRB could be represented by four sub-constructs: knowledge, severity, benefits, and action. The final version of the SRBS consists of 21 items. These items displayed high factor loadings, indicating a strong relationship between the items and their respective sub-constructs. The discriminant validity analysis revealed that the SRBS sub-constructs were distinct from each other. The SRBS scores were positively correlated with self-reported salt reduction practices. This demonstrates that individuals with higher SRBS scores were more likely to engage in actual salt reduction behaviors, indicating concurrent validity. CONCLUSION: The results illustrate that the Salt Reduction Behavior Scale is a robust and comprehensive instrument for assessing salt reduction behavior among hypertensive Chinese individuals. The scale's specific sub-constructs provide a detailed understanding of their knowledge, attitudes, and practices related to salt consumption. Healthcare professionals and policymakers can utilize this tool to tailor interventions and educational programs to encourage healthier dietary habits, thereby reducing the risk of cardiovascular diseases in China.

Factors influencing baby boomers' intention to choose a dish featuring plant-based meat alternatives (PBMA) at a restaurant: Findings from an online panel study.

The purpose of this study is to examine the psychosocial determinants of baby boomers'-born between 1946 and 1964- intention to choose a menu item featuring plant-based meat alternatives (PBMA) when dining out. The specific objectives are as follows: 1) to identify the baby boomer generation's health-related perceptions about PBMA, and 2) to examine the factors that influence baby boomers' intention to choose a dish featuring PBMA at a restaurant. A total of 174 responses obtained using the Qualtrics panel were analyzed with content analysis and partial least squares structural equation modeling (PLS-SEM). The findings identified various underlying perceptions of baby boomers toward PBMA, such as perceived health outcomes, perceived availability, and willingness to purchase. Furthermore, subjective norm, cues to action, and self-identity were found to be significant predictors of the intention to choose a menu item featuring PBMA when dining out. Theoretical and practical implications are discussed.

When increasing risk perception does not work. Using behavioral psychology to increase smoke alarm ownership.

The central question of our study is which determinants drive smoke alarm ownership and intention to purchase one, and whether we can increase smoke alarm ownership by addressing these determinants in a communication-based intervention. We first made an inventory of possible determinants for smoke alarm prevention by consulting prominent prevention behavior theories protection motivation theory and Health Belief Model and other relevant literature. We expanded this list of determinants based on interviews (n = 15) and used survey data representative for the Netherlands to decide to focus on smoke alarm ownership (rather than installation or maintenance). We then tested the determinants of smoke alarm ownership and buying intention in a survey (n = 622). Based on these results, we ran an A/B test (n = 310) of two messages to stimulate smoke alarm ownership: one emphasized the determinants we found to be strong predictors in the survey (know-how, social norm, annoyance) and one emphasized typical determinants that are often addressed in campaigns but were poor predictors in the survey (vulnerability, severity, benefits). Results showed that the message based on the strong determinants resulted in a significant increase in smoke alarm ownership (9.1%) compared to the control group (0.9%; p = 0.027), while the message using the typical determinants did not lead to significant effects. Taken together, our results give a promising direction for interventions to increase smoke alarm ownership, and above all, show that a comprehensive problem analysis for a specific target behavior is a necessary step to induce behavioral change.

Predicting the Posture of High-Rise Building Machines Based on Multivariate Time Series Neural Network Models.

High-rise building machines (HBMs) play a critical role in the successful construction of super-high skyscrapers, providing essential support and ensuring safety. The HBM's climbing system relies on a jacking mechanism consisting of several independent jacking cylinders. A reliable control system is imperative to maintain the smooth posture of the construction steel platform (SP) under the action of the jacking mechanism. Long Short-Term Memory (LSTM), Gated Recurrent Unit (GRU), and Temporal Convolutional Network (TCN) are three multivariate time series (MTS) neural network models that are used in this study to predict the posture of HBMs. The models take pressure and stroke measurements from the jacking cylinders as inputs, and their outputs determine the levelness of the SP and the posture of the HBM at various climbing stages. The development and training of these neural networks are based on historical on-site data, with the predictions subjected to thorough comparative analysis. The proposed LSTM and GRU prediction models have similar performances in the prediction process of HBM posture, with medians R2 of 0.903 and 0.871, respectively. However, the median MAE of the GRU prediction model is more petite at 0.4, which exhibits stronger robustness. Additionally, sensitivity analysis showed that the change in the levelness of the position of the SP portion of the HBM exhibited high sensitivity to the stroke and pressure of the jacking cylinder, which clarified the position of the cylinder for adjusting the posture of the HBM. The results show that the MTS neural network-based prediction model can change the HBM posture and improve work stability by adjusting the jacking cylinder pressure value of the HBM.

'It is in our hands-Why wait until you are sick?': Perceptions about diabetes prevention of Latina mothers in Mexico and the United States.

AIMS: This study aimed to understand the perceptions driving type 2 diabetes mellitus prevention and management behaviours of Mexican and Latina mothers in Mexico and the United States. METHODS: Low-income Mexican mothers in San Luis Potosí, Mexico and Latina mothers in Illinois, United States, were recruited by the Holistic Obesity Prevention Study (HOPS). Verbatim transcripts of the semistructured interviews conducted in Spanish (n = 24) and English (n = 1) were analysed using the Health Belief Model (HBM) framework. RESULTS: Of the 25 participants, 22 (88%) indicated 'knowing someone with diabetes'-specifically a father (n = 8), mother (n = 6) or grandparent (n = 7). Using the HBM, themes showed that mothers perceived: that Type 2 diabetes can happen to anyone, are attributable to genetic predisposition and may be driven by strong emotions (perceived susceptibility). Type 2 diabetes introduces severe comorbidities and emotional difficulties for people and their families (perceived severity). Adopting a healthier diet, exercising and staying in good spirits were recognized as benefits of Type 2 diabetes prevention (perceived benefits). The costs of food, challenges of exercising, dieting, modifying habits and time limitations were recognized as perceived costs. Cues to action included doctors' recommendations (external) and fear (internal). Mothers acknowledged they could live a healthy life by controlling their weight, exercising, adhering to treatments/medications and having the determination to carry-on (self-efficacy). CONCLUSIONS: Mothers sought to prevent Type 2 diabetes and live healthy lives, particularly, after receiving a diagnosis of gestational diabetes or when learning about their children's risks for Type 2 diabetes but perceived significant barriers to Type 2 diabetes prevention.

HIV testing and related factors among 50 years and older MSM in China: results from a cross-sectional study.

ABSTRACTHIV prevalence has increased continuously, and the age groups most afflicted by the epidemic have also shifted to people aged above 50 years. Informed by the theory of HBM, we aimed to investigate related factors associated with regular HIV testing behavior. Cross-sectional data were collected using online questionnaire from geosocial networking (GSN) mobile application (apps) for MSM during May 2020 (N = 1259). Data were analyzed by univariate and multivariate logistic regression. Around 62.0% (n = 781) had received HIV testing before. Participants being divorced/widowed (AOR = 1.5,95%CI:1.1-2.0), being aware of HIV/AIDS-related knowledge (AOR = 1.8,95%CI:1.4-2.3), having disclosed sexual orientation (AOR = 1.9,95%CI:1.5-2.5), ever had sexually transmitted infections symptoms (STIs)before (AOR = 2.4,95%CI:1.8-3.2), having had≥2 sexual partners (AOR = 1.8,95%CI:1.4-2.3) and with high self-efficacy (AOR = 1.1,95%CI:1.0-1.1) were more likely to receive HIV testing. Findings suggest that many Chinses MSM aged 50 and above have not been tested for HIV. Interventions for promoting HIV testing should focus on expanding scales of HIV/STIs screening, providing HIV/AIDS-related knowledge, creating a more supportive social environment and improving self-efficacy of HIV testing.

Comprehensive profiling and semi-quantification of exogenous chemicals in human urine using HRMS-based strategies.

Chemicals infiltrate our daily experiences through multiple exposure pathways. Human biomonitoring (HBM) is routinely used to comprehensively understand these chemical interactions. Historically, HBM depended on targeted screening methods limited to a relatively small set of chemicals with triple quadrupole instruments typically. However, recent advances in high-resolution mass spectrometry (HRMS) have facilitated the use of broad-scope target, suspect, and non-target strategies, enhancing chemical exposome characterization within acceptable detection limits. Despite these advancements, establishing robust and efficient sample treatment protocols is still essential for trustworthy broad-range chemical analysis. This study sought to validate a methodology leveraging HRMS-based strategies for accurate profiling of exogenous chemicals and related metabolites in urine samples. We evaluated five extraction protocols, each encompassing various chemical classes, such as pharmaceuticals, plastic additives, personal care products, and pesticides, in terms of their extraction recoveries, linearity, matrix effect, sensitivity, and reproducibility. The most effective protocol was extensively validated and subsequently applied to 10 real human urine samples using wide-scope target analysis encompassing over 2000 chemicals. We successfully identified and semi-quantified a total of 36 chemicals using an ionization efficiency-based model, affirming the methodology's robust performance. Notably, our results dismissed the need for a deconjugation step, a typically labor-intensive and time-consuming process.

Associations of PFAS-related plasma metabolites with cholesterol and triglyceride concentrations.

The wide-spread environmental pollutants per- and polyfluoroalkyl substances (PFAS) have repeatedly been associated with elevated serum cholesterol in humans. However, underlying mechanisms are still unclear. Furthermore, we have previously observed inverse associations with plasma triglycerides. To better understand PFAS-induced effects on lipid pathways we investigated associations of PFAS-related metabolite features with plasma cholesterol and triglyceride concentrations. We used 290 PFAS-related metabolite features that we previously discovered from untargeted liquid chromatography-mass spectometry metabolomics in a case-control study within the Swedish Västerbotten Intervention Programme cohort. Herein, we studied associations of these PFAS-related metabolite features with plasma cholesterol and triglyceride concentrations in plasma samples from 187 healthy control subjects collected on two occasions between 1991 and 2013. The PFAS-related features did not associate with cholesterol, but 50 features were associated with triglycerides. Principal component analysis on these features indicated that one metabolite pattern, dominated by glycerophospholipids, correlated with longer chain PFAS and associated inversely with triglycerides (both cross-sectionally and prospectively), after adjustment for confounders. The observed time-trend of the metabolite pattern resembled that of the longer chain PFAS, with higher levels during the years 2004-2010. Mechanisms linking PFAS exposures to triglycerides may thus occur via longer chain PFAS affecting glycerophospholipid metabolism. If the results reflect a cause-effect association, as implied by the time-trend and prospective analyses, this may affect the general adult population.

Urinary cotinine and exposure to passive smoke in children and adolescents in Germany - Human biomonitoring results of the German Environmental Survey 2014-2017 (GerES V).

Passive smoking is a preventable and significant cause of many serious health problems, with children being particularly at risk. In the fifth German Environmental Survey (GerES V), conducted from 2014 to 2017, information reflecting the extent of passive smoke exposure in children and adolescents was collected by interview-based questionnaires and human biomonitoring (HBM) analyses of cotinine in urine from 2260 participants, aged 3-17 years. Based on these population-representative data, we describe current passive smoke exposure stratified by different subgroups and identify specific exposure determinants using multivariate logistic regression. The questionnaire data revealed that 42% of children and adolescents lived with at least one smoker in the household. Quantifiable concentrations of cotinine could be detected in 56% of the participants. The overall median concentration of cotinine was 0.2 µg/L, with children and adolescents of low socioeconomic status found to be a group particularly affected by passive smoke with higher cotinine concentrations (median = 1.2 µg/L). In the multiple analysis, the most significant predictor of cotinine levels derived from the questionnaire was passive smoking at home (odds ratio (OR) 13.07 [95CI: 4.65, 36.70]). However, parental smoking and passive smoking among friends and relatives could also be identified as independent factors influencing elevated cotinine levels. The comparison between the previous cycle GerES IV (2003-2006) on 3-14-year-olds and GerES V shows that tobacco smoke exposure of children decreased significantly. This decrease is likely an effect of extensive non-smoker protection laws being enforced 2007-2008 on federal and state level. This is reflected by a halving of urinary cotinine concentrations. Nevertheless, our results indicate that passive smoke is still a relevant source of harmful pollutants for many children and adolescents in Germany, and thus support the need for further efforts to reduce passive smoke exposure, especially in the private environment.

Urinary pesticide mixture patterns and exposure determinants in the adult population from the Netherlands and Switzerland: Application of a suspect screening approach.

INTRODUCTION: Non-occupational sources of pesticide exposure may include domestic pesticide usage, diet, occupational exposure of household members, and agricultural activities in the residential area. We conducted a study with the ambition to characterize pesticide mixture patterns in a sample of the adult population of the Netherlands and Switzerland, using a suspect screening approach and to identify related exposure determinants. METHODS: A total of 105 and 295 adults participated in the Dutch and Swiss studies, respectively. First morning void urine samples were collected and analyzed in the same laboratory. Harmonized questionnaires about personal characteristics, pesticide-related activities, and diet were administered. Detection rates and co-occurrence patterns were calculated to explore internal pesticide exposure patterns. Censored linear and logistic regression models were constructed to investigate the association between exposure and domestic pesticide usage, consumption of homegrown and organic foods, household members' exposure, and distance to agricultural and forest areas. RESULTS: From the 37 detected biomarkers, 3 (acetamiprid (-CH2), chlorpropham (4-HSA), and flonicamid (-C2HN)) were detected in ≥40% of samples. The most frequent combination of biomarkers (acetamiprid-flonicamid) was detected in 22 (5.5%) samples. Regression models revealed an inverse association between high organic vegetable and fruit consumption and exposure to acetamiprid, chlorpropham, propamocarb (+O), and pyrimethanil (+O + SO3). Within-individual correlations in repeated samples (summer/winter) from the Netherlands were low (≤0.3), and no seasonal differences in average exposures were observed in Switzerland. CONCLUSION: High consumption of organic fruit and vegetables was associated with lower pesticide exposure. In the two countries, detection rates and co-occurrence were typically low, and within-person variability was high. Our study results provide an indication for target biomarkers to include in future studies aimed at quantifying urinary exposure levels in European adult populations.

Association of exposure to perfluoroalkyl substances (PFAS) and phthalates with thyroid hormones in adolescents from HBM4EU aligned studies.

BACKGROUND: Perfluoroalkyl substances (PFAS) and phthalates are synthetic chemicals widely used in various types of consumer products. There is epidemiological and experimental evidence that PFAS and phthalates may alter thyroid hormone levels; however, studies in children and adolescents are limited. AIM: To investigate the association of exposure to PFAS and phthalate with serum levels of thyroid hormones in European adolescents. METHODS: A cross-sectional study was conducted in 406 female and 327 male adolescents (14-17 years) from Belgium, Slovakia, and Spain participating in the Aligned Studies of the HBM4EU Project (FLEHS IV, PCB cohort, and BEA, respectively). Concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), free thyroxine (FT4), free triiodothyronine (FT3), and thyroid-stimulating hormone (TSH) were measured in sera from study participants, and urinary metabolites of six phthalates (DEP, DiBP, DnBP, BBzP, DEHP, and DiNP) and the non-phthalate plasticizer DINCH® were quantified in spot urine samples. Associations were assessed with linear regression and g-computational models for mixtures. Effect modification by sex was examined. RESULTS: In females, serum PFOA and the PFAS mixture concentrations were associated with lower FT4 and higher FT3 levels; MEP and the sums of DEHP, DiNP, and DINCH® metabolites (∑DEHP, ∑DiNP, and ∑DINCH) were associated with higher FT4; ∑DEHP with lower FT3; and the phthalate/DINCH® metabolite mixture with higher FT4 and lower FT3. In males, PFOA was associated with lower FT4 and the PFAS mixture with higher TSH levels and lower FT4/TSH ratio; MEP and ∑DiNP were associated with higher FT4; and MBzP, ∑DEHP, and the phthalate/DINCH® metabolite mixture with lower TSH and higher FT4/TSH. PFOA, mono-(2-ethyl-5-hydroxyhexyl) phthalate (OH-MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (oxo-MEHP), and monocarboxyoctyl phthalate (MCOP) made the greatest contribution to the mixture effect. CONCLUSIONS: Results suggest that exposure to PFAS and phthalates is associated with sex-specific differences in thyroid hormone levels in adolescents.

Time trend of exposure to secondhand tobacco smoke and polycyclic aromatic hydrocarbons between 1995 and 2019 in Germany - Showcases for successful European legislation.

Starting in 2002, regulations and legislative amendments in Germany focused on the non-smoker protection with several measures to reduce exposure to secondhand tobacco smoke (SHS). The present work aimed to evaluate the relationship between polycyclic aromatic hydrocarbons (PAHs) and SHS exposure and to determine to which extent enforced non-smoking regulations and smoking bans affected the exposure of the non-smoking population in Germany since their implementation in the early 2000s until today. For this purpose, cotinine and selected monohydroxylated PAHs (OH-PAHs) were analyzed by means of (UP)LC-MS/MS in 510 24-h-urine samples of the Environmental Specimen Bank collected over a time span of 24 years from 1995 to 2019. Median urinary cotinine levels were found to steadily and significantly decline by 82% from 1995 to 2019. A significant decrease of urinary 3-hydroxybenzo[a]pyrene (19%), 1-OH-pyrene (39%), 1-naphthol (66%), 1- (17%), 2- (25%), and 3-OH-phenanthrene (22%) was also observed throughout the same time span. The decline in urinary levels of cotinine and several OH-PAHs can most likely be attributed to smoking bans and regulations limiting SHS and PAH exposure. This study therefore emphasizes the relevance of human biomonitoring to investigate the exposure of humans to chemicals of concern, assess the effectiveness of regulatory measures, and help policies to enforce provisions to protect public health.

A time trend of urinary 4-methylbenzylidene camphor metabolites in young adults from Germany.

4-methylbenzylidene camphor (4-MBC) is used as a UV-B filter in cosmetics. Two oxidized metabolites of 4-MBC - 3-(4-carboxybenzylidene)camphor (cx-MBC) and 3-(4-carboxybenzylidene)-6-hydroxycamphor (cx-MBC-OH) - were analyzed in 250 24-h urine samples from young adults in Germany. The samples were from the German Environmental Specimen Bank (ESB) and represented exposure in the years 1995, 2005, 2010, 2015 and 2019. A UHPLC-MS/MS method enabled the sensitive determination of both metabolites, with limits of quantification at 0.15 µg L-1 (cx-MBC) and 0.30 µg L-1 (cx-MBC-OH), respectively. A temporal trend of the internal exposure to 4-MBC was clearly noticeable. The metabolite cx-MBC was frequently quantifiable at the beginning of the period: in 70% of the samples in 1995, and 56% in 2005. After 2005, urinary concentrations and detection rates of cx-MBC dropped to reach very low levels. In 2015 and 2019, the detection rate was only 2% and 0%, respectively. A similar trend was observed for cx-MBC-OH, though overall, this metabolite was detected less often and at lower concentration levels than cx-MBC. Nowadays, measurable levels of urinary 4-MBC metabolites are an extremely rare occurrence in Germany. These trends are consistent with the history of 4-MBC use by the cosmetic industry. The highest measured individual concentration of 16.20 µg L-1 (in a sample of the year 2005) was still more than 30 times below the health-based guidance value (HBM-I). An investigation of the ratios between both metabolites uncovered several features of the 4-MBC metabolism which have been essentially overlooked until now. In particular, stereochemical aspects should be explored in future studies. As urine was collected in autumn/winter in Northwestern Germany, the 4-MBC metabolites measured probably do not arise from sunscreen products in a narrow sense. They rather may reveal the use of other skin care products containing 4-MBC for UV protection as an added feature.

Consideration of pathways for immunotoxicity of per- and polyfluoroalkyl substances (PFAS).

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are of public health concern, because of their ubiquitous and extremely persistent occurrence, and depending on their structure, their bio-accumulative, mobile and toxic properties. Human health effects associated with exposure to PFAS include adverse effects on the immune system. In 2020, EFSA (the European Food Safety Authority) defined adverse effects on the immune system as the most critical effect for human health risk assessment, based on reduced antibody responses to childhood vaccines and similar effects observed in experimental animal studies. Likewise, the U.S. EPA (Environmental Protection Agency) considers PFAS-induced immunotoxicity, especially in children, as the critical effect for risk assessment. However, the mechanisms by which antibody concentrations are impacted are not completely understood. Furthermore, other targets of the immune system functions have been reported in the literature. OBJECTIVE: The aim of this review is to explore PFAS-associated immune-related effects. This includes, relevant mechanisms that may underlie the observed effects on the immune system, immunosuppression as well as immunoenhancement, such as i) modulation of cell signalling and nuclear receptors, such as NF-κB and PPARs; ii) alteration of calcium signalling and homoeostasis in immune cells; iii) modulation of immune cell populations; iv) oxidative stress and v) impact on fatty acid metabolism & secondary effects on the immune system. METHODS: A literature research was conducted using three databases (Web of Science, PubMed, and Scopus), which were searched in July 2021 for relevant studies published in the time frame from 2018 to 2021. In total, 487 publications were identified as potentially eligible and following expert-based judgement, articles relevant for mechanisms of PFAS induced immunotoxicity are discussed. CONCLUSIONS: Taken together, we show that there is substantial evidence from both in vitro and in vivo experimental as well as epidemiological studies, supporting that various PFAS, not only PFOA and PFOS, affect multiple aspects of the immune system. Timing of exposure is critical, because the developing immune system is especially vulnerable to toxic insults, resulting in a higher risk of particularly adverse immune effects but also other organs later in life.

Decision-making process of breastfeeding behavior in mothers with gestational diabetes mellitus based on health belief model.

BACKGROUND: Gestational diabetes mellitus (GDM) threatens GDM mothers and their offspring's health and breastfeeding is one of the most effective ways to decrease the risk. However, the prevalence of breastfeeding among GDM mothers is far from optimal and how GDM mothers develop their feeding behavior is still unclear. Thus, this study aimed to explore the formation of GDM mothers' breastfeeding behaviors based on the health belief model (HBM). METHODS: A questionnaire survey was conducted on 324 GDM mothers who have given birth within 6 months from January 1 to February 6, 2022. According to HBM, GDM mothers' knowledge, the perceived threat from GDM, the perceived value of breastfeeding, self-efficacy, social support and GDM mothers' breastfeeding behavior were measured. Exclusive breastfeeding (EBF) was defined as an infant who received only breast milk in the past 24 h before the survey. Structural equation modeling (SEM) was applied to explore how GDM mothers form their breastfeeding behaviors based on HBM. RESULTS: The prevalence of EBF among GDM mothers was 33.95%. GDM mothers had limited knowledge of GDM (average 63.14% correct answer to 7 questions), especially poor on the long-term effect of GDM (39.81%) and protective effect of breastfeeding (34.57%-45.99%). Although GDM mothers showed high perceived benefits (Mean: 3.35, SD: 0.46), high self-efficacy (Mean: 3.43, SD: 0.97) and high level of social support for breastfeeding (Mean: 3.74, SD: 0.74), the various barriers (Mean: 2.20, SD: 0.47) hindered their success in EBF. The SEM results showed that a higher level of social support and more self-efficacy of breastfeeding resulted in a higher likelihood of EBF, while the higher level of knowledge of GDM, perceived higher barriers and benefits of breastfeeding and higher susceptibility to GDM consequences led to less EBF. CONCLUSION: To promote EBF, physicians' education, emphasizing the protective effect of breastfeeding and how to correct breastfeeding, is highly recommended. In addition, social support for GDM mothers is also important to reduce their barriers to breastfeeding and help enhance self-efficacy in breastfeeding.

Determination of in vitro hepatotoxic potencies of a series of perfluoroalkyl substances (PFASs) based on gene expression changes in HepaRG liver cells.

Per- and polyfluoroalkyl substances (PFASs) are omnipresent and have been shown to induce a wide range of adverse health effects, including hepatotoxicity, developmental toxicity, and immunotoxicity. The aim of the present work was to assess whether human HepaRG liver cells can be used to obtain insight into differences in hepatotoxic potencies of a series of PFASs. Therefore, the effects of 18 PFASs on cellular triglyceride accumulation (AdipoRed assay) and gene expression (DNA microarray for PFOS and RT-qPCR for all 18 PFASs) were studied in HepaRG cells. BMDExpress analysis of the PFOS microarray data indicated that various cellular processes were affected at the gene expression level. From these data, ten genes were selected to assess the concentration-effect relationship of all 18 PFASs using RT-qPCR analysis. The AdipoRed data and the RT-qPCR data were used for the derivation of in vitro relative potencies using PROAST analysis. In vitro relative potency factors (RPFs) could be obtained for 8 PFASs (including index chemical PFOA) based on the AdipoRed data, whereas for the selected genes, in vitro RPFs could be obtained for 11-18 PFASs (including index chemical PFOA). For the readout OAT5 expression, in vitro RPFs were obtained for all PFASs. In vitro RPFs were found to correlate in general well with each other (Spearman correlation) except for the PPAR target genes ANGPTL4 and PDK4. Comparison of in vitro RPFs with RPFs obtained from in vivo studies in rats indicate that best correlations (Spearman correlation) were obtained for in vitro RPFs based on OAT5 and CXCL10 expression changes and external in vivo RPFs. HFPO-TA was found to be the most potent PFAS tested, being around tenfold more potent than PFOA. Altogether, it may be concluded that the HepaRG model may provide relevant data to provide insight into which PFASs are relevant regarding their hepatotoxic effects and that it can be applied as a screening tool to prioritize other PFASs for further hazard and risk assessment.

A walk in the PARC: developing and implementing 21st century chemical risk assessment in Europe.

Current approaches for the assessment of environmental and human health risks due to exposure to chemical substances have served their purpose reasonably well. Nevertheless, the systems in place for different uses of chemicals are faced with various challenges, ranging from a growing number of chemicals to changes in the types of chemicals and materials produced. This has triggered global awareness of the need for a paradigm shift, which in turn has led to the publication of new concepts for chemical risk assessment and explorations of how to translate these concepts into pragmatic approaches. As a result, next-generation risk assessment (NGRA) is generally seen as the way forward. However, incorporating new scientific insights and innovative approaches into hazard and exposure assessments in such a way that regulatory needs are adequately met has appeared to be challenging. The European Partnership for the Assessment of Risks from Chemicals (PARC) has been designed to address various challenges associated with innovating chemical risk assessment. Its overall goal is to consolidate and strengthen the European research and innovation capacity for chemical risk assessment to protect human health and the environment. With around 200 participating organisations from all over Europe, including three European agencies, and a total budget of over 400 million euro, PARC is one of the largest projects of its kind. It has a duration of seven years and is coordinated by ANSES, the French Agency for Food, Environmental and Occupational Health & Safety.

Human Papillomavirus Vaccine Acceptance (HPV-VA) and Vaccine Uptake (HPV-VU): assessing the impact of theory, culture, and trusted sources of information in a Hispanic community.

BACKGROUND: Human papillomavirus (HPV) is the most common sexually transmitted infection and is associated with many types of cancers that disproportionately impact Hispanics. An HPV vaccine is available for individuals ages 9-45 that can prevent up to 90% of HPV-associated cancers. The current study investigates factors associated with accepting the HPV vaccine in a predominately Hispanic community. METHODS: A cross-sectional study design with an online questionnaire was used to collect data from a community sample of adults between the ages 18-65 residing in a U.S./Mexico border city, El Paso, Texas. Theory-based factors (e.g., the Health Belief Model), culture-based factors (e.g., familism), and trusted sources of information were examined as predictors of HPV-vaccine acceptance (HPV-VA) and HPV-vaccine uptake (HPV-VU). RESULTS: Community members (N = 602, Mage = 34.65, SD = 9.79) who were predominately Hispanic (89.4%) and female (79.6%) participated in the study. Linear regression models revealed that HPV-VA was associated with household size, primary language, engagement in organizational activities, health-related community stigma, government trust, and the HBM theory-based factors: perceived benefits, perceived harm, and perceived severity. Logistic regression analyses revealed that HPV-VU was associated with household size, engagement in non-organizational activities, HPV trusted sources of information, and perceived safety. CONCLUSIONS: Adequate HPV vaccination uptake among all vaccine-eligible Hispanics is an important step to lessen the HPV-attributed cancer burden. Our hypothesis that theory-based factors would be associated with HPV-VA and HPV-VU was supported. Our findings have implications for designing trusted, theory-based, and culturally sensitive health communications and interventions to promote vaccines in minority underrepresented communities.