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.

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.

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.

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.

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.

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.

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.

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.

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.

Zirconia abutments for single-tooth implant restorations: a 10- to 11-year follow-up study.

OBJECTIVES: To evaluate the clinical outcome of custom-made zirconia abutments for implant-supported single-tooth restorations 10-11 years after insertion. MATERIAL AND METHODS: The study comprises a clinical examination of 23 patients with 30 restorations placed 10-11 years ago. Oral surgeons placed the implants. The prosthodontic treatment was provided at a prosthodontic specialist clinic. The restoration was either an all-ceramic crown for cementation or a screw-retained one-piece restoration with the veneering porcelain baked directly to the zirconia abutment. Besides the clinical and radiographic examination at the 10- to 11-year follow-up, the patients' records were scrutinized regarding clinical and radiographic data from insertion of the restoration up to the last visit at the clinic. RESULTS: The zirconia abutments performed well. Both technical and biological complications were rare; most patients were in general extremely satisfied with the restorations. No all-ceramic crowns fractured during the observation period. One implant was lost after 5½ years in service. There were no significant differences for changes in any of the soft tissue registrations or the peri-implant marginal bone level between the conventional two-piece abutment-crown restoration and the one-piece restoration. The peri-implant bone level changes from placement to the clinical examination 10-11 years later were small (mean 0.26 mm, SD 0.6 mm). CONCLUSIONS: Zirconia abutments for single-implant crowns demonstrated excellent technical and biological results over 10-11 years of function, and most patients were extremely satisfied with the aesthetics and the function of their single-implant restorations.

Topology of viral evolution.

The tree structure is currently the accepted paradigm to represent evolutionary relationships between organisms, species or other taxa. However, horizontal, or reticulate, genomic exchanges are pervasive in nature and confound characterization of phylogenetic trees. Drawing from algebraic topology, we present a unique evolutionary framework that comprehensively captures both clonal and reticulate evolution. We show that whereas clonal evolution can be summarized as a tree, reticulate evolution exhibits nontrivial topology of dimension greater than zero. Our method effectively characterizes clonal evolution, reassortment, and recombination in RNA viruses. Beyond detecting reticulate evolution, we succinctly recapitulate the history of complex genetic exchanges involving more than two parental strains, such as the triple reassortment of H7N9 avian influenza and the formation of circulating HIV-1 recombinants. In addition, we identify recurrent, large-scale patterns of reticulate evolution, including frequent PB2-PB1-PA-NP cosegregation during avian influenza reassortment. Finally, we bound the rate of reticulate events (i.e., 20 reassortments per year in avian influenza). Our method provides an evolutionary perspective that not only captures reticulate events precluding phylogeny, but also indicates the evolutionary scales where phylogenetic inference could be accurate.

Some issues related to evidence-based implantology.

This article reviews relevant dental literature to answer some frequent questions related to evidence-based implantology. There are hundreds of implant systems on the market, but the majority lack clinical documentation. Recommended number of implants for full-arch fixed prostheses is four or five in the mandible but at least six in the maxilla. Less expensive implant-retained overdentures make implant treatment available to a greater portion of edentulous subjects. Mandibular overdentures on two implants, and even one implant, have shown excellent long-term outcomes. In the maxilla, less than four implants are not recommended for good results. Single implant restorations have good prognosis, but placement of the implant should be postponed until adulthood. Osseointegrated implants have revolutionized clinical dentistry. However, in a global perspective, implants make up only a small part of all prosthodontic treatment. Knowledge and skill in conventional prosthodontics must be maintained as it will remain the most common part of the specialty.

Topological methods reveal high and low functioning neuro-phenotypes within fragile X syndrome.

Fragile X syndrome (FXS), due to mutations of the FMR1 gene, is the most common known inherited cause of developmental disability as well as the most common single-gene risk factor for autism. Our goal was to examine variation in brain structure in FXS with topological data analysis (TDA), and to assess how such variation is associated with measures of IQ and autism-related behaviors. To this end, we analyzed imaging and behavioral data from young boys (n = 52; aged 1.57-4.15 years) diagnosed with FXS. Application of topological methods to structural MRI data revealed two large subgroups within the study population. Comparison of these subgroups showed significant between-subgroup neuroanatomical differences similar to those previously reported to distinguish children with FXS from typically developing controls (e.g., enlarged caudate). In addition to neuroanatomy, the groups showed significant differences in IQ and autism severity scores. These results suggest that despite arising from a single gene mutation, FXS may encompass two biologically, and clinically separable phenotypes. In addition, these findings underscore the potential of TDA as a powerful tool in the search for biological phenotypes of neuropsychiatric disorders.

Topology based data analysis identifies a subgroup of breast cancers with a unique mutational profile and excellent survival.

High-throughput biological data, whether generated as sequencing, transcriptional microarrays, proteomic, or other means, continues to require analytic methods that address its high dimensional aspects. Because the computational part of data analysis ultimately identifies shape characteristics in the organization of data sets, the mathematics of shape recognition in high dimensions continues to be a crucial part of data analysis. This article introduces a method that extracts information from high-throughput microarray data and, by using topology, provides greater depth of information than current analytic techniques. The method, termed Progression Analysis of Disease (PAD), first identifies robust aspects of cluster analysis, then goes deeper to find a multitude of biologically meaningful shape characteristics in these data. Additionally, because PAD incorporates a visualization tool, it provides a simple picture or graph that can be used to further explore these data. Although PAD can be applied to a wide range of high-throughput data types, it is used here as an example to analyze breast cancer transcriptional data. This identified a unique subgroup of Estrogen Receptor-positive (ER(+)) breast cancers that express high levels of c-MYB and low levels of innate inflammatory genes. These patients exhibit 100% survival and no metastasis. No supervised step beyond distinction between tumor and healthy patients was used to identify this subtype. The group has a clear and distinct, statistically significant molecular signature, it highlights coherent biology but is invisible to cluster methods, and does not fit into the accepted classification of Luminal A/B, Normal-like subtypes of ER(+) breast cancers. We denote the group as c-MYB(+) breast cancer.

Is there a trend of decreasing prevalence of TMD-related symptoms with ageing among the elderly?

OBJECTIVE: Older adults have not been studied as much as younger ones regarding prevalence of TMD-related symptoms. The aim was to assess the prevalence of TMD-related symptoms in two population samples, 70 and 80 years old. MATERIALS AND METHODS: Identical questionnaires were in 2012 sent to all subjects born in 1932 and 1942 living in two Swedish counties. The response rate was 70.1%, resulting in samples of 5697 70- and 2922 80-year-old subjects. The questionnaire comprised 53 questions. Answers to questions on problems regarding TMD-related symptoms and awareness of bruxism were analysed. RESULTS: Twelve per cent of the women and 7% of the men in the 70-year-old group reported some, rather great or severe problems regarding TMD pain. In the 80-year-olds the prevalence was 8% and 7%, respectively. Subjects who had problems with TMJ sounds reported difficulty to open the jaw wide 6-times and TMJ pain 10-13-times more frequently than subjects without such problems. Changes of taste and awareness of bruxism were the only variables significantly associated with TMD symptoms in both age groups. Number of teeth was not significantly associated with any of the TMD-related symptoms. CONCLUSIONS: Most of the elderly subjects had no severe problems with TMD-related symptoms, but 12% of the 70-year-old women reported some, rather great or severe problems. The marked gender difference at age 70 had disappeared in the 80-year-old group. The prevalence was lower among the 80- compared with the 70-year-old subjects of both sexes. The results support the comorbidity between TMD-related symptoms and general health problems.

Use of implant-supported prostheses in edentulous mandibles among prosthodontists in Sweden.

The aim of this study was to investigate the production of mandibular implant-supported fixed and removable prostheses among prosthodontic specialists in Sweden and to compare the results with findings in a similar study made in 2001 (17). Questionnaires regarding treatment with mandibular implant prostheses during 20011 were mailed to all specialists in prosthodontics in Sweden (n = 156, according to available data). Of the 156 questionnaires, 129 (83%) were returned and of those 114 were completed. The reported number of treatments with mandibular implant-supported prostheses varied much among the specialists. Fixed implant prostheses were more common than overdentures (means 11 and 3, median values 8 and 2, respectively). However, the range was large for both alternatives. Ten (9%) of the specialists reported no treatment with fixed implant prostheses while 29 (25%) had not made any implant overdenture during 2011. The most common anchorage system for overdentures in 2011 (as well as in 2001) was two un-splinted implants with ball attachments or Locator abutments. The most common reasons for choosing overdenture treatment instead of a fixed implant prosthesis in 2011 were the reduced cost and the patient's main wish to improve denture retention. A majority of the prosthodontists (58%) reported that patients with implant overdentures were as satisfied as those with fixed implant-supported prostheses, whereas 40% claimed they were less satisfied. Two respondents (2%) considered that overdenture patients were more satisfied than those with a fixed prosthesis. It can be concluded that the general attitude among Swedish prosthodontists towards implant overdentures has not changed much during the 10-year period between the present and the previous investigation.An overdenture is still a seldom-used option in implant treatment of patients with edentulous mandibles in Sweden. Instead, a fixed implant-supported prosthesis continues to be the preferred option,

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.

Building Markov state models with solvent dynamics.

BACKGROUND: Markov state models have been widely used to study conformational changes of biological macromolecules. These models are built from short timescale simulations and then propagated to extract long timescale dynamics. However, the solvent information in molecular simulations are often ignored in current methods, because of the large number of solvent molecules in a system and the indistinguishability of solvent molecules upon their exchange. METHODS: We present a solvent signature that compactly summarizes the solvent distribution in the high-dimensional data, and then define a distance metric between different configurations using this signature. We next incorporate the solvent information into the construction of Markov state models and present a fast geometric clustering algorithm which combines both the solute-based and solvent-based distances. RESULTS: We have tested our method on several different molecular dynamical systems, including alanine dipeptide, carbon nanotube, and benzene rings. With the new solvent-based signatures, we are able to identify different solvent distributions near the solute. Furthermore, when the solute has a concave shape, we can also capture the water number inside the solute structure. Finally we have compared the performances of different Markov state models. The experiment results show that our approach improves the existing methods both in the computational running time and the metastability. CONCLUSIONS: In this paper we have initiated an study to build Markov state models for molecular dynamical systems with solvent degrees of freedom. The methods we described should also be broadly applicable to a wide range of biomolecular simulation analyses.