Prognostic assessment of 18F-boronophenylalanine positron emission tomography (BPA-PET) in salvage boron neutron capture therapy for malignant brain tumors.

Background: Boron neutron capture therapy (BNCT) stands out as a propitious anti-cancer modality. 18F-boronophenylalanine positron emission tomography (BPA-PET) holds the potential to ascertain the concentration of BPA within the tumor, enabling meticulous treatment planning and outcome evaluation. However, no studies have been conducted on comparing the outcomes of those treated with BNCT to those who did not undergo this therapy. This study endeavors to analyze the correlation between BPA-PET and BNCT in the context of malignant brain tumors, and assess the survival outcomes following BNCT. Methods: A cohort study was performed on patients who underwent BPA-PET between February 2017 and April 2022 in our hospital. Patients were stratified into two groups: those subjected to BNCT (Group 1) and those not (Group 2). The tumor to normal tissue (T/N) ratio derived from BPA-PET was set at 2.5. The findings were scrutinized based on clinical follow-up. Student's t-test and Chi-squared test were employed to discern differences between the groups. A cumulative survival curve was constructed employing the Kaplan-Meier method. Differences were considered statistically significant at P<0.05. Results: In total, 116 patients with T/N ratios obtained from BPA-PET were enrolled. BNCT was administered to 58 patients, while mortality was observed in 100 patients. The median overall survival (OS) for the two groups was 8.5 and 6.0 months, respectively. The cumulative OS exhibited no significant discrepancy between the two groups, nor in their T/N ratios. Within Group 1, 44 out of 58 (75.9%) patients exhibited T/N ratios exceeding 2.5. Excluding 3 patients who expired within 3 months, 55 out of 58 patients were evaluated for response after BNCT. The objective response rate (ORR) was 30.9%. Patients achieving ORR displayed substantially higher survival rates compared to those without (median OS 13.5 vs. 8.3 months, P=0.0021), particularly when T/N ratio exceeded 2.5 (median OS 14.8 vs. 9.0 months, P=0.0199). Conclusions: BNCT does not appear indispensable for prolonging the survival of patients afflicted with malignant brain tumors. Nevertheless, it proves advantageous when ORR is attained, a condition closely linked to the values of T/N ratio derived from BPA-PET.

Nitrogen-doped metal-free granular activated carbons as economical and easily separable catalysts for peroxymonosulfate and hydrogen peroxide activation to degrade bisphenol A.

The fabrication of low-cost, highly efficient, environmentally friendly, and easily separable metal-free heterogeneous catalysts for environmental remediation remains a challenge. In this study, granular nitrogen-doped highly developed porous carbons with a particle size of 0.25-0.30 mm were prepared by preoxidation and subsequent NH3 modification of a commercially available coconut-based activated carbon, and used to activate peroxymonosulphate (KHSO5) or hydrogen peroxide (H2O2) to degrade bisphenol A (BPA). The nitrogen-doped carbon (ACON-950) prepared by NH3 modification at 950 °C, with the addition of only 0.15 g/L could remove 100% of 50 mg/L BPA in 150 min, and more than 90% of the removed BPA was due to degradation. The removal rates of total organic carbon of ACON-950/KHSO5 and ACON-950/H2O2 systems reached 60.4% and 66.2% respectively, indicating the excellent catalytic activity of ACON-950. The reaction rate constant was significantly positively correlated with the absolute content of pyridinic N (N-6) and graphitic N (N-Q) and negatively and weakly positively correlated with pyrrolic N (N-5) and defects. Quenching experiments combined with electron paramagnetic resonance demonstrated that singlet oxygen was the dominant reactive oxidative species for BPA degradation. ACON-950 was characterized before and after the degradation reaction using N2 adsorption-desorption analyzer, Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). The results confirmed the prominent contribution of both the N-6 and N-Q to the catalytic performance of nitrogen-doped carbons. The reusability of ACON-950 and its application in actual water bodies further demonstrated its remarkable potential for the remediation of organic pollutants in wastewater.

Quality improvement project to reduce medicare 1-day write-offs due to inappropriate admission orders.

BACKGROUND: We identified that Stanford Health Care had a significant number of patients who after discharge are found by the utilization review committee not to meet Center for Mediare and Medicaid Services (CMS) 2-midnight benchmark for inpatient status. Some of the charges incurred during the care of these patients are written-off and known as Medicare 1-day write-offs. This study which aims to evaluate the use of a Best Practice Alert (BPA) feature on the electronic medical record, EPIC, to ensure appropriate designation of a patient's hospitalization status as either inpatient or outpatient in accordance with Center for Medicare and Medicaid services (CMS) 2 midnight length of stay benchmark thereby reducing the number of associated write-offs. METHOD: We incorporated a best practice alert (BPA) into the Epic Electronic Medical Record (EMR) that would prompt the discharging provider and the case manager to review the patients' inpatient designation prior to discharge and change the patient's designation to observation when deemed appropriate. Patients who met the inclusion criteria (Patients must have Medicare fee-for-service insurance, inpatient length of stay (LOS) less than 2 midnights, inpatient designation as hospitalization status at time of discharge, was hospitalized to an acute level of care and belonged to one of 37 listed hospital services at the time of signing of the discharge order) were randomized to have the BPA either silent or active over a three-month period from July 18, 2019, to October 18, 2019. RESULT: A total of 88 patients were included in this study: 40 in the control arm and 48 in the intervention arm. In the intervention arm, 8 (8/48, 16.7%) had an inpatient status designation despite potentially meeting Medicare guidelines for an observation stay, comparing to 23 patients (23/40, 57.5%) patients in the control group (p = 0.001). The estimated number of write-offs in the control arm was 17 (73.9%, out of 23 inpatient patients) while in the intervention arm was 1 (12.5%, out of 8 inpatient patient) after accounting for patients who may have met inpatient criteria for other reasons based on case manager note review. CONCLUSION: This is the first time to our knowledge that a BPA has been used in this manner to reduce the number of Medicare 1-day write-offs.

Microbiota analysis for risk assessment of xenobiotic exposure and the impact on dysbiosis: identifying potential next-generation probiotics.

On-going projects of the team are currently dealing with microbiota, xenobiotics, endocrine-disrupting chemicals (EDCs), obesity, inflammation and probiotics. The combination of diet, lifestyle and the exposure to dietary xenobiotics categorised into microbiota-disrupting chemicals (MDCs) could determine obesogenic-related dysbiosis. This modification of the microbiota diversity impacts on individual health-disease balance, inducing altered phenotypes. Specific, complementary, and combined prevention and treatments are needed to face these altered microbial patterns and the specific misbalances triggered. In this sense, searching for next-generation probiotics (NGP) by microbiota culturing, and focusing on their demonstrated, extensive scope and well-defined functions could contribute to counteracting and repairing the effects of obesogens. Therefore, EU-FORA project contributes to present a perspective through compiling information and key strategies for directed taxa searching and culturing of NGP that could be administered for preventing obesity and endocrine-related dysbiosis by (i) observing the differential abundance of specific microbiota taxa in obesity-related patients and analysing their functional roles, (ii) developing microbiota-directed strategies for culturing these taxa groups, and (iii) design and applying the successful compiled criteria from recent NGP clinical studies. New isolated or cultivable microorganisms from healthy gut microbiota specifically related to xenobiotic obesogens' neutralisation effects might be used as an NGP single strain or in consortia, both presenting functions and the ability to palliate metabolic-related disorders. Identification of holistic approaches for searching and using potential NGP, key aspects, the bias, gaps and proposals of solutions were also considered in this workplan.

Assessment of five typical environmental endocrine disruptors and thyroid cancer risk: a meta-analysis.

Introduction: There are conflicting reports on the association between environmental endocrine disruptors (EEDs) and thyroid cancer. This meta-analysis aimed to elucidate the relationship between EEDs and thyroid cancer. Methods: We searched for epidemiological studies on EEDs and thyroid cancer published in PubMed and Web of Science up to December 2022. We then screened the articles that could extract data on EEDs concentration levels in both thyroid cancer patients and healthy controls. We excluded articles that could not calculate effect sizes, focused on other thyroid diseases, or lacked controls. Standardized mean difference (SMD) was calculated to analyze the association between EEDs and thyroid cancer. We measured the heterogeneity among the included studies using I2, assessed publication bias by Egger's and Begg's test, and evaluated article quality using the Newcastle-Ottawa Quality Score (NOS). In the end, fifteen eligible case-control studies were included. Results: Our comprehensive analysis revealed that polychlorinated biphenyls (PCBs) were negatively associated with thyroid cancer{ SMD = -0.03, 95% confidence interval (CI) = (-0.05, -0.00), P = 0.03}, while polybrominated diphenyl ethers (PBDEs), phthalates (PAEs), and heavy metals were positively associated with thyroid cancer{PBDEs: SMD = 0.14, 95%CI = (0.04, 0.23), P = 0.007; PAEs: SMD = 0.30, 95%CI = (0.02, 0.58), P = 0.04; heavy metals: SMD = 0.21, 95%CI = (0.11, 0.32), P < 0.001}. We did not find a statistically significant relationship between bisphenol A (BPA) and thyroid cancer. Most of the included studies did not show publication bias, except for those on PCBs. Discussion: Our results indicate that exposure to certain EEDs, such as PBDEs, PAEs, and heavy metals, increases the risk of thyroid cancer. However, further large-scale epidemiological studies and mechanism studies are needed to verify these potential relationships and understand the underlying biological mechanisms.

Human health risk assessment for consumption of microplastics and plasticizing substances through marine species.

A special characteristic of MP (microplastics) in the ocean is they may act as carriers of additives specific to the plastic materials used in their manufacture, such as plasticizers, among which Bisphenol-A (BPA), bis (2-ethylhexyl) phthalate (DEHP), dybuthyl phthalate (DBP). Both MP as the plasticizers were searched in composite samples of mangrove cockle (Anadara tuberculosa), Stolzmann's weakfish (Cynoscion stolzmanni) and arched swimming crab (Callinectes arcuatus). Extraction of MP was done through physical-chemical techniques and identification was carried out employing the techniques of light microscopy, energy dispersive spectrometer (EDS), scanning electron microscope (SEM) and Raman spectroscopy; the sizes of MP obtained were between 0.5 µm and 106 µm, the following average results being obtained: for Arched swimming crab 4.0 ± 1.0 MP/g; mangrove cockle 3.3 ± 2.9 MP/g; and for Stolzmann's weakfish, the average was 2.4 ± 1.3 MP/g; the most observed shapes were fibers and irregular segments; the most identified MP was polyethylene terephthalate (PET). Regarding extraction and quantification of plasticizers, the extraction stage was carried out using QuEChERS tubes; and the identification and quantification with gas chromatography coupled to a mass spectrometer (GC-MS). Regarding the plasticizing substances, DEHP was found in detectable levels in all the samples; BPA was found in 84% of the composite samples analyzed; DBP was found in 50% of them, of the analyzed samples 34% were positive for the 3 analytes. The dietary exposure of people to plasticizers was calculated and for BPA the exposure obtained was compared with respect to the TDI (tolerable intake dose) for pregnant women and the new TDI proposed by EFSA in 2021 according to the estrogenic effect of this substance in the fetus. The objective of the work was to determine if a relationship could be established between both PM and plasticizers, which gave a positive relationship.

Combined reverse osmosis and UV/H2O2 treatment of aqueous solutions of bisphenol A and 17α-ethinylestradiol: assessment of estrogenic activity.

Bisphenol-A (BPA) and 17α-ethinylestradiol (EE2) are considered endocrine disrupting compounds (EDC) and they may be harmful to the normal functioning of endocrine systems of humans and animals. Moreover, the presence of these compounds in superficial and groundwater may represent serious risks, even in low concentrations like ng·L-1. The objectives of this study were to remove BPA and EE2 from solutions containing a mixture of these compounds in ultrapure water at low concentrations through reverse osmosis (RO) membrane combined with a UV/H2O2 process. Furthermore, to assess the estrogenic activity reduction after such treatments, in vitro recombinant yeast-estrogen screen (YES) assay was used. The removal efficiencies of target micropollutants increased with the increase of H2O2 dosage. For RO permeate stream, they enhanced from 91% to 96% for EE2 and from 76% to 90% for BPA while, for the concentrate stream, from 70% to 81% for EE2 and 41% to 84% for BPA as the H2O2 concentration were increased from 100 to 1000 µg·L-1. The OH radicals' generation was the dominant factor in the degradation of EDC during the UV/H2O2 treatment since the photolysis itself was not enough to degrade BPA or EE2. The estrogenic activity reduction after UV/H2O2 treatment was high, ranging from 92% to 98% for the permeate stream and from 50% to 93% for the concentrate stream. The EE2 was responsible for the whole observed estrogenic activity since BPA does not present estrogenicity, by in vitro YES assay, in the concentrations observed.

Assessment of BPA and BPS exposure in the general population in Guangzhou, China - Estimation of daily intakes based on urinary metabolites.

Human exposure to bisphenol A (BPA) and bisphenol S (BPS) has garnered considerable global health concerns. In this paper, the daily intake (DI) of BPA and BPS in the general population of Guangzhou, China, were back-calculated using the biomarkers BPA glucuronides (BPA-G) and BPS glucuronides (BPS-G), respectively. The biomarkers are preferable to total BPA and BPS measurements because they are not susceptible to external contamination. A total of 1440 urine samples were gathered from the general population in Guangzhou, China, which were classified by age and sex into 36 pooled urine samples. 100% and 98% of pooled urine samples contained BPA-G and BPS-G at median values of 1.57 and 0.38 ng/mL, respectively. Based on urinary BPA-G and BPS-G concentrations, we determined the median DI of BPA and BPS to be 31.07 and 7.37 ng/(kg bw*d), respectively, and the highest values to be 106.77 ng/(kg bw*d) and 18.19 ng/(kg bw*d), respectively. Furthermore, our results showed that for the entire dataset, the DI of BPA and BPS were considerably greater in males than in females (p < 0.01)and declined significantly with age (p < 0.05). For risk assessment, the estimated DIs of BPA and BPS were much lower than the European Food Safety Authority' s (EFSA) the temporary acceptable reference dose of 4 µg/(kg bw*d) advised for BPA, suggesting that the exposure risk of BPA and BPS for Guangzhou population is within a controllable safety range. This is the first study to investigate BPA and BPS exposure in the general population of Guangzhou, China, on the basis of urinary metabolites.

Human health risk assessment of bisphenol A (BPA) through meat products.

Meat and meat products are often consumed in our daily diet, providing essential nutrients. Contamination by chemical hazards, including bisphenol A (BPA) in meat products, is a concern and is continuously monitored. BPA is well-known for its endocrine-disrupting properties, which may cause potential toxicological effects on reproductive, nervous, and immune systems. Dietary consumption is the main route of BPA exposure, and meat products are a major contributor. BPA exposure from meat consumption is the focus of this review. This review found that BPA has been widely detected in canned and non-canned meat products. BPA in canned meat is assumed to be predominantly from migration from can coatings. Relatively low levels are observed in non-canned products, and the source of contamination in these products has yet to be definitively identified. A recent European Food Safety Authority (EFSA) draft opinion has proposed to lower the tolerable daily intake of BPA from 4 µg kg body weight (bw)-1 day-1 to 0.04 ng kg body weight (bw)-1 day-1, therefore potential health risks need to be addressed. This review has investigated potential contamination at the farm, industrial processes, and retail levels. Data gaps in the literature are also identified to improve future food safety in the meat industry. Also, a unified risk assessment strategy has been proposed. Further understanding of BPA migration in meat products is needed as a part of the exposure assessment to reduce potential risk, and more data on the dose-response relationship will help comprehend potential adverse health effects of BPA on humans. This research will inform the public, meat producers and processing industry, and policymakers on potential exposure to BPA and risk reduction measures, thus, ensuring food safety.

Human Biomonitoring Guidance Values (HBM-GVs) for Bisphenol S and Assessment of the Risk Due to the Exposure to Bisphenols A and S, in Europe.

Within the European Joint Programme HBM4EU, Human Biomonitoring Guidance Values (HBM-GVs) were derived for several prioritised substances. In this paper, the derivation of HBM-GVs for the general population (HBM-GVGenPop) and workers (HBM-GVworker) referring to bisphenol S (BPS) is presented. For the general population, this resulted in an estimation of the total urinary concentration of BPS of 1.0 µg/L assuming a 24 h continuous exposure to BPS. For workers, the modelling was refined in order to reflect continuous exposure during the working day, leading to a total urinary concentration of BPS of 3.0 µg/L. The usefulness for risk assessment of the HBM-GVs derived for BPS and bisphenol A (BPA) is illustrated. Risk Characterisation Ratios (RCRs) were calculated leading to a clear difference between risk assessments performed for both bisphenols, with a very low RCR regarding exposure to BPA., contrary to that obtained for BPS. This may be due to the endocrine mediated endpoints selected to derive the HBM-GVs for BPS, whereas the values calculated for BPA are based on the temporary Tolerable Daily Intake (t-TDI) from EFSA set in 2015. A comparison with the revised TDI recently opened for comments by EFSA is also discussed. Regarding the occupational field, results indicate that the risk from occupational exposure to both bisphenols cannot be disregarded.

Assessment of Exposure to Di-(2-ethylhexyl) Phthalate (DEHP) Metabolites and Bisphenol A (BPA) and Its Importance for the Prevention of Cardiometabolic Diseases.

Exposomics analyses have highlighted the importance of biomonitoring of human exposure to pollutants, even non-persistent, for the prevention of non-communicable diseases such as obesity, diabetes, non-alcoholic fatty liver disease, atherosclerosis, and cardiovascular diseases. Phthalates and bisphenol A (BPA) are endocrine disrupting chemicals (EDCs) widely used in industry and in a large range of daily life products that increase the risk of endocrine and cardiometabolic diseases especially if the exposure starts during childhood. Thus, biomonitoring of exposure to these compounds is important not only in adulthood but also in childhood. This was the goal of the LIFE-PERSUADED project that measured the exposure to phthalates (DEHP metabolites, MEHP, MEHHP, MEOHP) and BPA in Italian mother-children couples of different ages. In this paper we describe the method that was set up for the LIFE PERSUADED project and validated during the proficiency test (ICI/EQUAS) showing that accurate determination of urinary phthalates and BPA can be achieved starting from small sample size (0.5 mL) using two MS techniques applied in cascade on the same deconjugated matrix.

Biomarker-assisted assessment of aquatic health using the cosmopolitan common carp, Cyprinus carpio (L): a case study of bisphenol-A exposures.

Monitoring aquatic health from environmental pollutants is critical, none more so than bisphenol-A (BPA), a ubiquitous endocrine-disrupting chemical (EDC). The present study brings out the responses of selected transcripts, hormone levels, and tissue histomorphology in a widely distributed fish species Cyprinus carpio (Linn.), following exposure to environmentally relevant (10, 100 ng/L) and higher (1000 ng/L) concentration of BPA. The response of cyp19a1a, cyp19a1b, and c3 significantly decreased, while that of vtg increased in their respective tissue domains. The hematological parameters TEC, Hb, and Hct decreased significantly in contrast to TLC (p < 0.05) at all exposure concentrations, whereas none of the erythrocytic indices (MCV, MCH, and MCHC) was perturbed. The steroidogenic hormone levels, such as estradiol and progesterone, increased significantly with increasing BPA concentrations. In contrast, the testosterone and all the thyroid hormones (T3, T4, and TSH) were suppressed significantly (p < 0.05). At the histological level, the BPA induced chondrocyte proliferation, which was accompanied by hemorrhage of the gill lamellae, increased melanomacrophagic centers (MMCs), and degeneration of tubules and fluid accumulation in the kidney. In parallel, binucleated hepatocytes and inflammations were prominent in the liver. Collectively, the histomorphology confirmed induction of degenerative effects in all the tissues investigated, while the cyclic responses of biochemical markers suggest an ability to regulate the impacts. However, a chronic exposure could result in overriding the endemic reproductive pathways with potential population-level effects. In conclusion, the study identified multiple molecular, cellular, and physiological markers that could be employed to detect early signs of BPA and more broadly EDC exposures. These markers in combination with a wide distribution of C. carpio should allow comparative studies of pollutants at environmental concentrations.

A critical assessment of the estrogenic potency of benzyl salicylate.

Benzyl salicylate (BS) is a natural ingredient of essential oils and a widely used fragrance chemical. A number of in vitro screening studies have evaluated the estrogenic potential of BS with ambiguous results. Lack of dose-response information for the positive control 17ß-estradiol (E2) in most studies makes an assessment of the relative potency and efficacy challenging. Notwithstanding this difficulty, BS has been added as the only fragrance ingredient to the list of the first 14 substances to be screened as potential endocrine disruptors by the European Scientific Committee for Consumer Safety (SCCS) and it is included in the Community rolling action plan (CoRAP) of the European REACH regulation to be assessed for the same property. Here we review all literature evidence and present new data to quantify the in vitro potency and efficacy of BS vs. E2 with full dose response analysis in both an estrogen response element (ERE) depending reporter gene assay and in the MCF7 cell proliferation (E-screen) assay. In both assays, very similar results for BS were found. BS is a partial agonist exhibiting 35-47 % maximal efficacy and it is active only close to the cytotoxic concentration. The extrapolated concentration to achieve 50 % efficacy is 21'000'000 higher as compared to E2 in the reporter gene assay. A ca. 36'000'000 higher concentration of BS as compared to E2 is required to reach equivalent partial cell proliferation stimulation in the MCF7 proliferation assay. This potency is significantly below the agonistic activity of known chemicals which cause estrogenic effects in in vivo assays. Importantly, in this study the weak agonistic activity is for the first time directly related to the activity of E2 in a full quantitative comparison in human cell lines which may help ongoing evaluations of BS by regulatory bodies.

Serial right heart catheter assessment between balloon pulmonary angioplasty sessions identify procedural factors that influence response to treatment.

BACKGROUND: Balloon pulmonary angioplasty (BPA) is delivered as a series of treatments for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) however, there is little published data on the procedural determinants of outcome. METHODS: Pre- and post-BPA clinical and hemodynamic data, as well as serial hemodynamic and procedural data at each BPA session were evaluated to determine patient and procedure-related factors that influence hemodynamic response. RESULTS: Per procedure data from 210 procedures in 84 patients and per patient data from 182 procedures in 63 patients with completed treatment and 3-month follow-up were analyzed. A median of 3 (range 1-6) BPA procedures treating a median of 2 segments per procedure (range 1-3) were performed per patient with a median interval between procedures of 42 (range 5-491) days. Clinical outcome correlated with hemodynamic change (pulmonary vascular resistance [ΔPVR] vs Cambridge Pulmonary Hypertension Outcome Review [CAMPHOR] symptom score: p < 0.001, Pearson's r = 0.48, n = 49). Responders to BPA had more severe disease at baseline and 37.5 % of non-responders were post-PEA. There was a dose-response relationship between per procedure and total number of segments treated and hemodynamic improvement (ΔPVR: 1 segment: -0.9%, 2: -14.5%, 3 or more: -16.1%, p < 0.001). Treating totally occluded vessels had a greater hemodynamic effect (mean pulmonary artery pressure [ΔmPAP]: sessions with occlusion: -8.0%, without occlusion treated: -3.2%, p < 0.05) without an increased complication rate. CONCLUSIONS: The magnitude of clinical benefit is related to the hemodynamic effect of BPA which in turn is related to the number of segments treated and lesion severity. Patients who were post-PEA were less likely to respond to BPA.

Urinary bisphenol A and its alternatives among pregnant women: Predictors and risk assessment.

BACKGROUND: Exposure to bisphenol A (BPA) has been associated with various adverse health outcomes. Recently, an increasing concern on its alternatives such as bisphenol S (BPS) and bisphenol F (BPF) has been aroused due to the restriction use of BPA. Few studies have identified predictors of exposure to BPA alternatives and assessed their health risks. OBJECTIVE: The aim of this study was to identify predictors of BPA and its alternatives and to assess their health risks among pregnant women. METHODS: We detected first morning urinary concentrations of BPA and its alternatives (BPS and BPF) among 1097 pregnant women from an established Chinese cohort. A questionnaire was conducted to obtain demographic characteristics, dietary habits, and lifestyles. We examined the predictors of creatinine-adjusted urinary BPA and its alternatives concentrations using multivariable linear regression. Risk assessment of exposure to BPA and its alternatives was calculated based on the estimated of daily intake (EDI). RESULTS: Geometric means of creatinine-adjusted urinary BPA, BPF, and BPS were 0.92, 0.12, and 0.08 µg/g creatinine, respectively. Pregnant women from Wuhan had lower concentrations of BPA, BPF, and ∑BPs (sum of BPA, BPF, and BPS) than those from Xiaogan. Intake of fried food was related to higher concentrations of BPA, and intake of pickled food was associated with higher concentrations of BPF and ∑BPs. The maximum EDI values for exposure to BPA, BPF, BPS, and ∑BPs ranged from 5.6428 to 13.3356 nmol/kg body weight/day, which were below the tolerable daily intake (TDI) for BPA defined by the European Food Safety Authority (EFSA) (18 nmol/kg body weight/day). The maximum hazard index (HI) value was 0.7409. CONCLUSION: Several predictors identified in this study may inform public recommendations to reduce exposure to BPA and its alternatives.

Exposure assessment of bisphenol A by drinking coffee from plastic cups.

BACKGROUND: Human exposure to plastic and Bisphenol-A (BPA) is very wide in food or beverage containers and baby bottles that have contacted polycarbonate and epoxy resin. Currently a traditional beverage in Arabian culture is served in plastic cups instead of glass cups in different occasions. OBJECTIVE: To evaluate the possible BPA leach from the grade 5 drinking coffee plastic cups into the coffee and whether the use of plastic cups instead of glass ones to serve hot Arabian coffee poses a health risk. MATERIALS AND METHODS: Oral administration of such coffee to three different groups of rats were undertaken. Each group consisted of 10 males and 10 females. The first group (G1) was gavaged 1.5 ml of hot water in glass cups. The second group (G2) was gavaged 1.5 ml of hot water in plastic cups while the third one (G3) was gavaged 1.5 ml of Arabian coffee in plastic cups. Serum concentrations of Bisphenol-A were measured 4 weeks later. Complete postmortem examination was conducted and representative tissue samples were subjected to histopathological evaluation. RESULTS: In the control group receiving water kept in a glass cup had 24 ± 2 µg/L serum concentration and the second group was 36 ± 4 µg/L while in the third group was 29 ± 6 µg/L. No significant postmortem changes or histopathological findings were present in the studied animals. CONCLUSIONS: Bisphenol-A can be leached from food-grade plastic cups into hot drinks within short period of time, posing a significant impact to public health.

Risk assessment of predicted serum concentrations of bisphenol A in children and adults following treatment with dental composite restoratives, dental sealants, or orthodontic adhesives using physiologically based pharmacokinetic modeling.

Bisphenol A (BPA) is a chemical used to manufacture bisphenol A glycidyl methacrylate (BisGMA). BisGMA has been used for decades in dental composite restoratives, sealants, and adhesives. Based on published studies, exposure to low concentrations of BPA are possible from dental and orthodontic devices. The serum BPA concentrations arising from such devices and oral doses were predicted using a PBPK model in children and adult females based on 1) published extraction data for cured and uncured 3M ESPE Filtek Supreme Ultra Flowable, 3M ESPE Filtek Bulk Fill Restorative, and 3M ESPE Clinpro Sealant and 2) published 20% ethanol/water and water rinsate data following orthodontic application with 3M ESPE Transbond MIP Primer and 3M ESPE Transbond XT Adhesive. Predicted oral exposure to BPA arising from these dental and orthodontic devices is low (median <10 ng/treatment) and predicted serum BPA concentrations were also low (<10-4 nM). Even the maximum predicted exposure in this study (533.2 ng/treatment) yields a margin of exposure of 7.5 relative to the EFSA t-TDI (4 µg/kg-day) and is only 2.8% of the daily BPA exposure for the US population in a 58-kg woman (15,660 ng/day). Therefore, the exposure to BPA arising from the 3M ESPE dental and orthodontic devices evaluated in this study is negligible relative to daily BPA exposure in the general population and these potential BPA sources do not constitute a risk to patients.

Toxicological risk assessment of bisphenol a released from dialyzers under simulated-use and exaggerated extraction conditions.

Bisphenol A (BPA) belongs to a group of chemicals used in the production of polycarbonate, polysulfone, and polyethersulfone which are used, among other applications, in the manufacture of dialyzers. While exposure to BPA is widespread in the general population, dialysis patients represent a population with potentially chronic parenteral BPA exposures. To assess the potential risk of BPA exposure to dialysis patients through dialyzer use, exposure estimates were calculated based on BPA levels measured by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry following extractions from dialyzers manufactured by Fresenius Medical Care. Extraction conditions included both simulated-use leaching and exaggerated extractions to evaluate possible leachable and extractable BPA, respectively, from the devices. The mean BPA concentrations were 3.6 and 108.9 ppb from simulated-use and exaggerated extractions, respectively, from polycarbonate-containing dialyzers. No BPA was detected from polypropylene-containing dialyzers. Margins of Safety (MOS) were calculated to evaluate the level of risk to patients from estimated BPA exposure from the dialyzers, and the resulting MOS were 229 and 45 for simulated-use and exaggerated extractions, respectively. The findings suggest that there is an acceptable level of toxicological risk to dialysis patients exposed to BPA from use of the dialyzers tested in the current study.

Galectin-3, GDF-15, and sST2 for the assessment of disease severity and therapy response in patients suffering from inoperable chronic thromboembolic pulmonary hypertension.

PURPOSE: This study examined sST2, GDF-15, and galectin-3 as indicators of disease severity and therapy response in chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: This study included 57 inoperable CTEPH patients who underwent balloon pulmonary angioplasty and 25 controls without cardiovascular disease. Biomarker levels were examined in relation to advanced hemodynamic impairment [tertile with worst right atrial pressure (RAP) and cardiac index], hemodynamic therapy response [normalized hemodynamics (meanPAP ≤25 mmHg, PVR ≤3 WU and RAP ≤6 mmHg) or a reduction of meanPAP ≥25%; PVR ≥ 35%, RAP ≥25%]. RESULTS: GDF-15 [820 (556-1315) pg/ml vs. 370 (314-516) pg/ml; p < 0.001] and sST2 [53.7 (45.3-74.1) ng/ml vs. 48.7 (35.5-57.0) ng/ml; p = 0.02] were higher in CTEPH patients than in controls. At baseline, a GDF-15 level ≥1443 pg/ml (AUC 0.88; OR 31.4) and a sST2 level ≥65 ng/ml (AUC 0.80; OR 10.9) were associated with advanced hemodynamic impairment. At follow-up GDF-15 ≤ 958 pg/ml (AUC = 0.74, OR 18) identified patients with optimal hemodynamic therapy response and ≤760 pg/ml (AUC = 0.79, OR 14). CONCLUSION: GDF-15 and sST2 levels are higher in CTEPH and identified patients with advanced hemodynamic impairment. Further, decreased GDF-15 levels at follow-up were associated with hemodynamic therapy response. The diagnostic strength was not superior to NT-proBNP.

Bisphenol A shapes children's brain and behavior: towards an integrated neurotoxicity assessment including human data.

Concerns about the effects of bisphenol A (BPA) on human brain and behavior are not novel; however, Grohs and colleagues have contributed groundbreaking data on this topic in a recent issue of Environmental Health. For the first time, associations were reported between prenatal BPA exposure and differences in children's brain microstructure, which appeared to mediate the association between this exposure and children's behavioral symptoms. Findings in numerous previous mother-child cohorts have pointed in a similar worrying direction, linking higher BPA exposure during pregnancy to more behavioral problems throughout childhood as assessed by neuropsychological questionnaires. Notwithstanding, this body of work has not been adequately considered in risk assessment. From a toxicological perspective, results are now available from the CLARITY-BPA consortium, designed to reconcile academic and regulatory toxicology findings. In fact, the brain has consistently emerged as one of the most sensitive organs disrupted by BPA, even at doses below those considered safe by regulatory agencies such as the European Food Safety Authority (EFSA). In this Commentary, we contextualize the results of Grohs et al. within the setting of previous epidemiologic and CLARITY-BPA data and express our disquiet about the "all-or-nothing" criterion adopted to select human data in a recent EFSA report on the appraisal methodology for their upcoming BPA risk assessment. We discuss the most relevant human studies, identify emerging patterns, and highlight the need for adequate assessment and interpretation of the increasing epidemiologic literature in this field in order to support decision-making. With the aim of avoiding a myopic or biased selection of a few studies in traditional risk assessment procedures, we propose a future reevaluation of BPA focused on neurotoxicity and based on a systematic and comprehensive integration of available mechanistic, animal, and human data. Taken together, the experimental and epidemiologic evidence converge in the same direction: BPA is a probable developmental neurotoxicant at low doses. Accordingly, the precautionary principle should be followed, progressively implementing stringent preventive policies worldwide, including the banning of BPA in food contact materials and thermal receipts, with a focus on the utilization of safer substitutes.