Exploring BPA alternatives - Environmental levels and toxicity review.

Bisphenol A alternatives are manufactured as potentially less harmful substitutes of bisphenol A (BPA) that offer similar functionality. These alternatives are already in the market, entering the environment and thus raising ecological concerns. However, it can be expected that levels of BPA alternatives will dominate in the future, they are limited information on their environmental safety. The EU PARC project highlights BPA alternatives as priority chemicals and consolidates information on BPA alternatives, with a focus on environmental relevance and on the identification of the research gaps. The review highlighted aspects and future perspectives. In brief, an extension of environmental monitoring is crucial, extending it to cover BPA alternatives to track their levels and facilitate the timely implementation of mitigation measures. The biological activity has been studied for BPA alternatives, but in a non-systematic way and prioritized a limited number of chemicals. For several BPA alternatives, the data has already provided substantial evidence regarding their potential harm to the environment. We stress the importance of conducting more comprehensive assessments that go beyond the traditional reproductive studies and focus on overlooked relevant endpoints. Future research should also consider mixture effects, realistic environmental concentrations, and the long-term consequences on biota and ecosystems.

Advancing Precision Medicine: Algebraic Topology and Differential Geometry in Radiology and Computational Pathology.

Precision medicine aims to provide personalized care based on individual patient characteristics, rather than guideline-directed therapies for groups of diseases or patient demographics. Images-both radiology- and pathology-derived-are a major source of information on presence, type, and status of disease. Exploring the mathematical relationship of pixels in medical imaging ("radiomics") and cellular-scale structures in digital pathology slides ("pathomics") offers powerful tools for extracting both qualitative and, increasingly, quantitative data. These analytical approaches, however, may be significantly enhanced by applying additional methods arising from fields of mathematics such as differential geometry and algebraic topology that remain underexplored in this context. Geometry's strength lies in its ability to provide precise local measurements, such as curvature, that can be crucial for identifying abnormalities at multiple spatial levels. These measurements can augment the quantitative features extracted in conventional radiomics, leading to more nuanced diagnostics. By contrast, topology serves as a robust shape descriptor, capturing essential features such as connected components and holes. The field of topological data analysis was initially founded to explore the shape of data, with functional network connectivity in the brain being a prominent example. Increasingly, its tools are now being used to explore organizational patterns of physical structures in medical images and digitized pathology slides. By leveraging tools from both differential geometry and algebraic topology, researchers and clinicians may be able to obtain a more comprehensive, multi-layered understanding of medical images and contribute to precision medicine's armamentarium.

Xerostomia in 75-85-year-olds: A longitudinal population study.

BACKGROUND: Xerostomia can pose significant problems for many elderly people. OBJECTIVES: To investigate longitudinal changes in prevalence, persistence, progression, remission and incidence of xerostomia from age 75 to 85 years. METHODS: All 75-year-olds (born 1932) from two Swedish counties, Sweden were mailed a questionnaire in 2007 (N = 5195), and again in 2017 when they were aged 85 (N = 3323). The total response rates at ages 75 and 85 years were 71.9% and 60.8%, respectively. A 'panel', those who participated in both surveys, comprised 1701 individuals (response rate 51.2%). RESULTS: At age 85, there was almost a doubling of self-reported 'yes often' xerostomia compared with age 75 (from 6.2% to 11.3%) and was almost twice as common in women than men (p < .001). When combining 'yes often'/'yes sometimes', xerostomia increased from 33.4% to 49.0%, and was more so among women (p < .001). Xerostomia was commoner at night than daytime, with 23.4% reporting 'yes often' night-time xerostomia at 85 compared with 18.5% at 75, and was also higher in women (p < .001). Progression rates for daytime and night-time xerostomia were 34.2% and 38.1%, for persistence 67.4% and 68.6%, and for remission 24.4% and 16.5%. Average yearly incidence was higher in women than men for both daytime (3.6% vs. 3.2%) and night-time (3.9% vs. 3.7%). Regression analyses predicted protective factors for developing xerostomia reported at age 75 as good general and oral health, absence of medications/intraoral symptom/s, good chewing function and social interaction. CONCLUSIONS: Xerostomia increases markedly from age 75 to 85 years.

Topological data analysis in medical imaging: current state of the art.

Machine learning, and especially deep learning, is rapidly gaining acceptance and clinical usage in a wide range of image analysis applications and is regarded as providing high performance in detecting anatomical structures and identification and classification of patterns of disease in medical images. However, there are many roadblocks to the widespread implementation of machine learning in clinical image analysis, including differences in data capture leading to different measurements, high dimensionality of imaging and other medical data, and the black-box nature of machine learning, with a lack of insight into relevant features. Techniques such as radiomics have been used in traditional machine learning approaches to model the mathematical relationships between adjacent pixels in an image and provide an explainable framework for clinicians and researchers. Newer paradigms, such as topological data analysis (TDA), have recently been adopted to design and develop innovative image analysis schemes that go beyond the abilities of pixel-to-pixel comparisons. TDA can automatically construct filtrations of topological shapes of image texture through a technique known as persistent homology (PH); these features can then be fed into machine learning models that provide explainable outputs and can distinguish different image classes in a computationally more efficient way, when compared to other currently used methods. The aim of this review is to introduce PH and its variants and to review TDA's recent successes in medical imaging studies.

Temporal changes and gender differences related to orofacial symptoms in two cohorts of 75-year-old Swedish subjects examined in 2007 and 2017: A repeated cross-sectional study.

OBJECTIVES: To compare two cohorts of 75-year-old persons, born 10 years apart, in regard to reported symptoms related to temporomandibular disorders (TMD) and orofacial complaints with special reference to gender differences. MATERIAL AND METHODS: In 2007, a questionnaire comprising questions on social factors, general and oral health, and a series of attitude-related questions was mailed to all individuals born in 1932 living in two Swedish counties (N = 5195), and in 2017 to all born in 1942 (N = 7204). The response rate for the cohort examined in 2007 was 71.9% (n = 3735) and 70.7% (n = 5091) for the cohort examined in 2017. Bivariate statistical analyses were applied. RESULTS: Reported bruxism and pain from the temporomandibular joint were significantly higher in the 1942 cohort compared to the 1932 cohort, while reports of oral lesions and daytime dry mouth were lower. Women reported problems significantly more frequently in most of the domains investigated in both 2007 and 2017, that is, TMD, burning mouth, sensitive teeth, oral lesions, taste changes, daytime/night-time dry mouth, except bad breath. CONCLUSIONS: TMD-related symptoms increased while complaints from oral lesions and daytime mouth dryness decreased between 2007 and 2017. Temporal changes were otherwise few, but the findings underline the gender inequalities that exist, to the disadvantage of women. This must be considered when planning for clinical care/dental education to appropriately address the needs of older people.

Comparative study of left atrium epicardial fat tissue pattern using persistent homology approach.

OBJECTIVE: Atrial Fibrillation (A-fib) is an abnormal heartbeat condition in which the heart races and beats in an uncontrollable way. It is observed that the presence of increased epicardial fat/fatty tissue in the atrium can lead to A-fib. Persistent homology using topological features can be used to recapitulate enormous amounts of spatially complicated medical data into a visual code to identify a specific pattern of epicardial fat tissue with non-fat tissue. Our aim is to evaluate the topological pattern of left atrium epicardial fat tissue with non-fat tissue. RESULTS: A topological data analysis approach was acquired to study the imaging pattern between the left atrium epicardial fat tissue and non-fat tissue patches. The patches of eight patients from CT images of the left atrium heart were used and categorized into "left atrium epicardial fat tissue" and "non-fat tissue" groups. The features that distinguish the "epicardial fat tissue" and "non-fat tissue" groups are extracted using persistent homology (PH). Our result reveals that our proposed research can discriminate between left atrium epicardial fat tissue and non-fat tissue. Specifically, the range of Betti numbers in the epicardial tissue is smaller (0-30) than the non-fat tissue (0-100), indicating that non-fat tissue has good topology.

Satisfaction with dental appearance in two cohorts of 75-year-olds examined in 2007 and 2017: A repeated cross-sectional study.

BACKGROUND: Satisfaction with dental appearance plays an important role in the self-esteem and psychological well-being of the elderly, the significance of which the attending dentist may not always be fully cognisant of. OBJECTIVES: To assess the level of satisfaction with dental appearance, its associated factors and temporal changes in two cohorts of 75-year-old Swedes born 10 years apart. METHODS: In 2007, a questionnaire was mailed to all those living in Örebro and Östergötland counties, Sweden, who were born in 1932 (n = 5195), and in 2017 to all born in 1942 (n = 7204). The evaluation was carried out with a global question 'Are you satisfied with the appearance of your teeth?', and four attitude-related statements about dental appearance. RESULTS: About 80% in both cohorts were 'very satisfied' or 'to large extent satisfied' with their dental appearance. The 1932 cohort was significantly more concerned about their dental appearance than the 1942 cohort, and women were generally also significantly more concerned than men. In the regression analysis, 'very satisfied' with dental appearance was predicted by good chewing efficiency, having complete dentures, no impact from Oral Impacts on Daily Performance, disagreement that 'minor esthetic imperfections of the teeth have no importance, only they should function well', better perceived general health than same-aged peers and belonging to the 1932 cohort. CONCLUSION: Satisfaction with dental appearance among 75-year-olds was generally high, with attitudes varying by gender and temporally. Women and the earlier-born generation (1932) were more concerned about dental appearance than men and the later-born generation (1942), respectively.

Prediction of xerostomia in a 75-year-old population: A 25-year longitudinal study.

OBJECTIVES: To follow the same individuals from age 50 up to 75 years to report on prevalence, persistence, progression, remission, incidence and predictors for xerostomia. METHODS: A questionnaire was distributed to all 50-years-olds (1992) in two Swedish counties (N = 8888) and repeated at the age of 65 (2007) and 75 years (2017). 3060 individuals responded on all three occasions (response rate 42.5%). Xerostomia was assessed with two questions. Additional questions addressed inter alia general/oral health and oral function. RESULTS: Reported prevalence of daytime xerostomia were 23.3% and 14.7%, and 39.5% and 27.5% in women and men, age 50 and 75, respectively. Night-time prevalence was higher. At age 50, 27.4% women and 24.0% men reported having dry mouth, and at age 75, 61.0% and 53.8%, respectively. At all time points, women reported significantly more xerostomia than men. Progression (deterioration) was common, and persistence (continuing presence) was high, while 25-year incidence for daytime xerostomia was 16.2% and 12.8%, and 33.6% and 29.8% at night-time, for women and men, respectively. Based on reports at age 50, regression analyses showed that prediction for developing xerostomia during the observation period, and reporting xerostomia at age 75 years, were female gender, impaired general health, chewing, jaw opening and intraoral problems, dissatisfaction with dental appearance, low education and having white/plastic filling. CONCLUSIONS: Xerostomia is common in older people, especially at night and in women. It can be predicted by diverse factors reported earlier in life. CLINICAL SIGNIFICANCE: Clinicians need to be made aware of that elderly often suffers from dry mouth so that they can recommend effective measures to eliminate or ease the patients accompanying symptoms and also exclude or lessen possible negative impact on oral health related to xerostomia.

Gene co-expression network analysis reveals mechanisms underlying ozone-induced carbamazepine toxicity in zebrafish (Danio rerio) embryos.

Sewage effluent ozonation can reduce concentrations of chemical pollutants including pharmaceutical residues. However, the formation of potentially toxic ozonation byproducts (OBPs) is a matter of concern. This study sought to elucidate toxicity mechanisms of ozonated carbamazepine (CBZ), an anti-epileptic drug frequently detected in sewage effluents and surface water, in zebrafish embryos (Danio rerio). Embryos were exposed to ozonated and non-ozonated CBZ from 3 h post-fertilization (hpf) until 144 hpf. Embryotoxicity endpoints (proportion of dead and malformed embryos) were assessed at 24, 48, and 144 hpf. Heart rate was recorded at 48 hpf. Exposure to ozonated CBZ gave rise to cardiovascular-related malformations and reduced heart rate. Moreover, embryo-larvae exposed to ozonated CBZ displayed a lack of swim bladder inflation. Hence, the expression patterns of CBZ target genes involved in cardiovascular and embryonal development were investigated through a stepwise gene co-expression analysis approach. Two co-expression networks and their upstream transcription regulators were identified, offering mechanistic explanations for the observed toxicity phenotypes. The study presents a novel application of gene co-expression analysis elucidating potential toxicity mechanisms of an ozonated pharmaceutical with environmental relevance. The resulting data was used to establish a putative adverse outcome pathway (AOP).

Topological data analysis reveals genotype-phenotype relationships in primary ciliary dyskinesia.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a heterogeneous inherited disorder caused by mutations in approximately 50 cilia-related genes. PCD genotype-phenotype relationships have mostly arisen from small case series because existing statistical approaches to investigating relationships have been unsuitable for rare diseases. METHODS: We applied a topological data analysis (TDA) approach to investigate genotype-phenotype relationships in PCD. Data from separate training and validation cohorts included 396 genetically defined individuals carrying pathogenic variants in PCD genes. To develop the TDA models, 12 clinical and diagnostic variables were included. TDA-driven hypotheses were subsequently tested using traditional statistics. RESULTS: Disease severity at diagnosis, measured by forced expiratory volume in 1 s (FEV1) z-score, was significantly worse in individuals with CCDC39 mutations (compared to other gene mutations) and better in those with DNAH11 mutations; the latter also reported less neonatal respiratory distress. Patients without neonatal respiratory distress had better preserved FEV1 at diagnosis. Individuals with DNAH5 mutations were phenotypically diverse. Cilia ultrastructure and beat pattern defects correlated closely to specific causative gene groups, confirming these tests can be used to support a genetic diagnosis. CONCLUSIONS: This large scale, multi-national study presents PCD as a syndrome with overlapping symptoms and variations in phenotype according to genotype. TDA modelling confirmed genotype-phenotype relationships reported by smaller studies (e.g. FEV1 worse with CCDC39 mutation) and identified new relationships, including FEV1 preservation with DNAH11 mutations and diversity of severity with DNAH5 mutations.

Modeling Bioavailable Concentrations in Zebrafish Cell Lines and Embryos Increases the Correlation of Toxicity Potencies across Test Systems.

Linking cellular toxicity to low-tier animal toxicity and beyond is crucial within the adverse outcome pathway concept and the 3R framework. This study aimed to determine and compare the bioavailable effect concentrations in zebrafish cell lines and embryos. Acute, short-term toxicity (48 h) of eight veterinary pharmaceuticals was measured in two zebrafish cell lines (hepatocytes, fibroblasts) and zebrafish embryos. Seven endpoints of cytotoxicity were recorded. The fish embryo acute toxicity test was modified by adding sublethal endpoints. Chemical distribution modeling (mass balance) was applied to compute the bioavailable compound concentrations in cells (Cfree) and embryos (Cint;aq) based on nominal effect concentrations (Cnom). Effect concentration ratios were calculated (cell effects/embryo effects). A low correlation was observed between cytotoxicity and embryo toxicity when nominal concentrations were used. Modeled bioavailable effect concentrations strongly increased correlations and placed regression lines close to the line of unity and axis origin. Cytotoxicity endpoints showed differences in sensitivity and predictability. The hepatocyte cell line depicted closer proximity to the embryo data. Conclusively, the high positive correlation between the cell- and embryo-based test systems emphasizes the appropriate modulation of toxicity when linked to bioavailable concentrations. Furthermore, it highlights the potential of fish cell lines to be utilized in integrated testing strategies.

Changes in conditions related to reported oral and general health over a ten-year period as reflected in two cohorts of 75-year-old subjects examined in 2007 and 2017.

BACKGROUND: The rapidly ageing and increasingly dentate population puts great demands on society regarding the provision of adequate medical and dental care facilities. OBJECTIVES: To present changes in reported demographic, general and oral health factors in two cohorts of 75 year olds in 2007 and 2017, and to analyse factors associated with self-reported number of remaining teeth and chewing efficiency. MATERIAL AND METHODS: All 75-year-old people living in two Swedish counties received a questionnaire in 2007 and in 2017. The response rates in 2007 and in 2017 were 71.9% (n = 3735) and 70.7% (n = 5091), respectively. Reported number of teeth was clinically validated in a selected subgroup. RESULTS: The 2017 cohort reported significantly better general health and dental state. Edentulousness was 7.8% in 2007 and 2.3% in 2017, while 'very good' chewing efficiency was 55.2% and 60.5%, respectively. Born outside Sweden, single living, not feeling healthy and smoking predicted reduced number of teeth in both cohorts. Impaired chewing efficiency in both cohorts was predicted by being born outside Sweden, lower education, not feeling healthy, reduced number of teeth and denture wearing. CONCLUSIONS: Seventy-five-year-old people in Sweden reported much better oral and general health in 2017 compared to 2007. In 2017, 75% had practically all natural teeth present and only 2% were edentulous. This development of an increasingly dentate and partially dentate ageing population will put high demands on the oral healthcare system and will need adapting undergraduate/postgraduate education and management strategies to meet the requirements of the elderly.

Carbamazepine Ozonation Byproducts: Toxicity in Zebrafish (Danio rerio) Embryos and Chemical Stability.

Carbamazepine (CBZ) is an anticonvulsant medication with highly persistent properties in the aquatic environment, where it has the potential to affect nontarget biota. Because CBZ and many other pharmaceuticals are not readily removed in conventional sewage treatment plants (STP), additional STP effluent treatment technologies are being evaluated and implemented. Whole effluent ozonation is a prospective method to remove pharmaceuticals such as CBZ, yet knowledge on the toxicity of CBZ ozonation byproducts (OBPs) is lacking. This study presents, for the first time, in vivo individual and mixture toxicity of four putative OBPs, that is, carbamazepine 10,11-epoxide, 10,11-Dihydrocarbamazepine, 1-(2-benzaldehyde)-4-hydro-(1H,3H)-quinazoline-2-one (BQM), and 1-(2-benzaldehyde)-(1H,3H)-quinazoline-2,4-dione (BQD) in developing zebrafish (Danio rerio) embryos. BQM and BQD were isolated from the ozonated solution as they were not commercially available. The study confirmed that the OBP mixture caused embryotoxic responses comparable to that of ozonated CBZ. Individual compound embryotoxicity assessment further revealed that BQM and BQD were the drivers of embryotoxicity. OBP chemical stability in ozonated CBZ water solution during 2 week dark storage at 22 °C was also assessed. The OBP concentrations remained over time, except for BQD which decreased by 94%. Meanwhile, ozonated CBZ persistently induced embryotoxicity over 2 week storage, potentially illustrating environmental concern.

Self-reported dry mouth in 50- to 80-year-old Swedes: Longitudinal and cross-sectional population studies.

Xerostomia is a common condition among elderly. The objectives were to examine prevalence, persistence, progression, yearly incidence of xerostomia, associated background factors and its influence on oral impacts on daily performances (OIDP) in 50- to 80-year-old people. In 1992, a questionnaire was sent to all 50-year-old (n = 8888) and in 2007 to all 75-year-old persons (n = 5195) living in two Swedish counties. In 2012, the same questionnaire was sent to both age cohorts, now 70- and 80-year-old. Response rate was for the 50-, 70- 75- and 80-year-old groups 71.4%, 72.2%, 71.9% and 66.4%, respectively. In the 50- to 70-year-old sample, 40.3% of the participants answered all five examinations and in the 75-80 group 49.5% (intact samples). In all age groups, xerostomia was significantly more prevalent in women than in men. At age 80, "often mouth dryness at night" was reported by 24.3% and 16.2% of women and men, respectively. Prevalence increased with age and was more frequent at night-time. Persistence of xerostomia was reported by 61.4%-77.5%, progression by 11.5%-33.0% and remission by 5.7%-11.3%. Average yearly incidence was 0.99%-3.28%. Xerostomia was more prevalent in those who reported a negative impact on OIDP. Highest odd ratios for xerostomia were burning mouth (OR 12.0), not feeling healthy (OR 5.1) and medicine usage (OR 3.9). Xerostomia is common in older age, persistence is high and progression common. The comorbidity between xerostomia, oral health problems and impaired general health needs to be taken into consideration when providing dental care to elderly patients.

Behavioural effects and bioconcentration of per- and polyfluoroalkyl substances (PFASs) in zebrafish (Danio rerio) embryos.

Per- and polyfluoroalkyl substances (PFASs) are contaminants of emerging concern (CECs) that cause concern regarding their environmental impact and risk to human health. In this study, zebrafish (Danio rerio) embryos were exposed to PFASs for six days, to investigate behaviour toxicity and bioconcentration factor (BCF). Nine individual PFASs (five C4-C8 perfluoroalkyl carboxylates (PFCAs) (PFPeA, PFHxA, PFHpA, PFOA, PFNA), three C4, C6 and C8 perfluoroalkyl sulfonates (PFSAs) (PFBS, PFHxS, PFOS) and 6:2 fluorotelomersulfonate (6:2 FTSA)) and a mixture of these were investigated at seven concentrations ranging from environmentally relevant to acutely toxic levels. In exposed embryos, significant differences were found in total swimming distance (PFHpA, PFOA, PFNA, PFHxS, PFOS, 6:2 FTSA, PFAS mixture), burst activity (PFOA, PFNA, PFHxS, PFOS, PFAS mixture) and startle response (PFNA, PFHxS, PFOS, PFAS mixture). Toxicity was only observed at concentrations well above environmental levels. The toxicity of the PFAS mixture generally followed that of the individual substances, but the mixture reduced the potencies of individual PFASs. BCF was determined for all nine PFASs and ranged between 0.9 (PFPeA) and 2700 (PFOS). Long-chain PFASs (C8) and PFASs with sulfonate as an active group showed the greatest toxic potential, while short-chain PFASs (C6 and C7) also caused significant behaviour alterations and accumulated in the embryos. To our knowledge, this is the first study to compare the behaviour toxicity of a PFAS mixture with that of the individual PFASs. Follow-up studies are needed to identify the mechanistic responses to PFAS mixtures.

Effects of antidepressants with different modes of action on early life stages of fish and amphibians.

Drugs are excreted from the human body as both original substances and as metabolites and enter aquatic environment through waste water. The aim of this study was to widen the current knowledge considering the effects of waterborne antidepressants with different modes of action-amitriptyline, venlafaxine, sertraline-on embryos of non-target aquatic biota-fish (represented by Danio rerio) and amphibians (represented by Xenopus tropicalis). The tested concentrations were 0.3; 3; 30; 300 and 3000 µg/L in case of amitriptyline and venlafaxine and 0.1; 1; 10; 100 and 1000 µg/L for sertraline. Test on zebrafish embryos was carried out until 144 h post fertilization, while test on Xenopus embryos was terminated after 48 h. Lethal and sublethal effects as well as swimming alterations were observed at higher tested concentrations that are not present in the environment. In contrast, mRNA expression of genes related to heart, eye, brain and bone development (nkx2.5, otx 2, bmp4 and pax 6) seems to be impacted also at environmentally relevant concentrations. In a wider context, this study reveals several indications on the ability of antidepressants to affect non target animals occupying environments which may be contaminated by such compounds.

Effect-based environmental monitoring for thyroid disruption in Swedish amphibian tadpoles.

It is well-known that the metamorphosis process in amphibians is dependent on thyroid hormones. Laboratory studies have shown that several environmental contaminants can affect the function of thyroid hormones leading to alterations in the amphibian metamorphosis. The basic idea of the present study was to elucidate if the amphibian metamorphosis might be a useful tool as biomarker for effect-based environmental monitoring, examining wild tadpoles for potential thyroid hormone disruption. A laboratory test was performed to identify the responses from exposure to 6-propylthiouracil (PTU), which has a well-known mechanism on the thyroid system, on Swedish tadpoles from the Rana genus. This was followed by an environmental monitoring study where tadpoles of Rana arvalis, R. temporaria, and Bufo bufo were sampled from various sites in Sweden. Morphological data such as body weight, histopathological measurements of the thyroid glands, and environmental parameters were recorded. The results revealed that Rana tadpoles respond similar as other amphibians to PTU exposure, with interrupted development and increased size relative to the developmental stage. Data on some wild tadpoles showed similar features as the PTU exposed, such as high body weight, thus suggesting potential thyroid disrupting effects. However, histological evaluation of thyroid glands and pesticide analyses of the water revealed no clear evidence of chemical interactions. To a minor degree, the changes in body weight may be explained by natural circumstances such as pH, forest cover, and temperature. The present study cannot fully explain whether the high body weights recorded in some tadpoles have natural or chemical explanations. However, the study reveals that it is clearly achievable to catch tadpoles in suitable stages for the use in this type of biomonitoring and that the use of these biomarkers for assessment of thyroid disruption seems to be highly relevant.

Thyroid disruption properties of three indoor dust chemicals tested in Silurana tropicalis tadpoles.

Indoor dust contains a multitude of industrial chemicals, and ingestion of dust is considered an important exposure route to organic contaminants. Some of these contaminants have been shown to interfere with the thyroid system, which may result in significant consequences on public health. The amphibian metamorphosis is a thyroid hormone-dependent process, which can be used as an in vivo model for studies on thyroid hormone-disrupting potency. Three contaminants of indoor dust were tested on metamorphosing Silurana (Xenopus) tropicalis tadpoles. The tested chemicals were Tris (1,3-dichloroisopropyl) phosphate (TDCiPP), tetrabromobisphenol-A (TBBPA) and propylparaben (PrP). Measurements reflecting general growth, development progress and thyroid epithelial cell height were performed on the exposed tadpoles as well as chemical analyses of the exposure water. It was shown that TDCiPP acts as a thyroid hormone-disrupting chemical in metamorphosing tadpoles by causing increased epithelial cell height in thyroid glands after exposure to a nominal concentration of 0.010 mg/L and in higher concentrations. TBBPA caused reductions in general growth of tadpoles at the nominal concentration 0.125 mg/L, and PrP caused acute toxicity at the nominal concentration 12.5 mg/L. However, no evident indications of specific thyroid-disrupting effects caused by TBBPA or PrP were observed.

Embryotoxicity of ozonated diclofenac, carbamazepine, and oxazepam in zebrafish (Danio rerio).

Pharmaceutical residues are polluting the surface water environments worldwide. Sewage and wastewater treatment, therefore, needs to be improved in order to remove pharmaceutical residues from the effluent. One such treatment improvement is effluent ozonation. Even though ozonation has proven to be very efficient in reducing pharmaceutical parent compound concentrations in wastewater effluents, much remains unclear regarding potentially toxic ozonation by-product (OBP) formation. In this study, we sought to elucidate the aquatic toxicity of ozonated pharmaceuticals in zebrafish (Danio rerio) embryos in a static 144 h post fertilization (hpf) fish embryotoxicity (ZFET) assay. Three pharmaceuticals commonly detected in wastewater effluents, i.e. carbamazepine, diclofenac, and oxazepam, were selected for testing. Toxicity was assessed before and after 1 min ozonation (0.053 mg L-1 peak O3 concentration) and 10 min ozonation (0.147 mg L-1 peak O3 concentration). Chemical analysis showed that carbamazepine and diclofenac were largely removed by ozone (90 ±â€¯11% and 97 ±â€¯3.8%), whereas oxazepam was removed to a lesser extent (19 ±â€¯5.7%). The ZFET assay revealed diverging toxicities. Diclofenac embryotoxicity decreased with increasing ozonation. Oxazepam did not cause embryotoxicity in the ZFET assay either pre- or post ozonation, but larvae swimming activity was affected at 144 hpf. Carbamazepine embryotoxicity, on the other hand, increased with increasing ozonation. Chemical analysis showed the formation of two OBPs (carbamazepine-10,11-epoxide and 10,11-dihydrocarbamazepine), possibly explaining the increased embryotoxicity. The results of this study highlight the importance of new chemical and toxicological knowledge regarding the formation of OBPs in post-ozonated effluents.

An International Survey among Prosthodontists of the Use of Mandibular Implant-Supported Dental Prostheses.

PURPOSE: To evaluate the use of implant-supported overdentures (IOD) and implant-supported fixed dental prostheses (IFDP) in patients with edentulous mandibles among international prosthodontists. MATERIALS AND METHODS: A questionnaire was sent by e-mail to all clinically active prosthodontists in the International College of Prosthodontists with questions related to implant treatment of the edentulous mandible performed in 2015. RESULTS: One hundred and sixteen prosthodontists from 33 countries responded to the questionnaire. The vast majority of the responding prosthodontists was faculty or worked in private practice, and the great majority had performed treatment with mandibular implant-supported dental prostheses; however, two thirds of the respondents reported that <20% of the implant patients in their clinic had received treatment related to edentulous mandibles. The majority reported using 2 implants (84%), while 13% used 4 for overdenture retention. There were great variations regarding retention systems used for mandibular IODs; the most common was individual Locator attachments. Cost was considered the most common reason to choose mandibular IOD, There was a wide variation of materials used for mandibular IFDPs. The most common combination included milled titanium frameworks and acrylic resin teeth. CONCLUSIONS: This survey, completed by 116 prosthodontists from 33 countries, showed that implant treatment for edentulous mandibles is common, but there was great variation among the respondents regarding amount of treatments performed, design, and materials used for the implant prostheses.