Remineralization strategies in oral hygiene: a position paper of Italian Society of Oral Hygiene Sciences-S.I.S.I.O. working group

Background/Objective: The clinical conditions that lead to an alteration of the enamel structure are numerous. The diet high in sugars and acidifying substances, psychological stress that triggers parafunctional behaviors, the reduced intake of fiber-rich foods or alkalizing substances, together with other factors, contribute to demineralization of the tooth enamel. Dental mineralizing products on the current market are distinguished according to the dosage form, the active ingredient, the release technology, clinical indications and patient choice. Currently, it is necessary to propose to oral health professionals a guide to orient themselves in this chaotic choice, in order to prefer the most effective product for their own clinical target. Methods: Italian Society of Oral Hygiene Sciences-S.I.S.I.O. is one of the leading scientific Italian societies representing those dental hygienists working with high-quality standards and in agreement with scientific evidence: in the last year, the SISIO working group has carried out a study focused on remineralizing agents in dentistry, in order to give an authoritative point of view to indicate a guideline in the decision process of the choice of a remineralizing agent. We will report the results pointed out from the last consensus meeting in 2017. Results: We have reported the good the bad and the ugly have been discussed in a critical discussion of such topic. Conclusion: The SISIO experience has been reported in this position paper with the aim to serve as a useful aid in the daily choice of the clinical steps to perform, when dental professionals need to treat demineralized teeth. Keywords: Dental Hygiene, Oral health, Dental Remineralizing, Enamel, Toothpaste, Mouthwash

Challenges in predicting stabilizing variations: An exploration

An open challenge of computational and experimental biology is understanding the impact of non-synonymous DNA variations on protein function and, subsequently, human health. The effects of these variants on protein stability can be measured as the difference in the free energy of unfolding (ΔΔG) between the mutated structure of the protein and its wild-type form. Throughout the years, bioinformaticians have developed a wide variety of tools and approaches to predict the ΔΔG. Although the performance of these tools is highly variable, overall they are less accurate in predicting ΔΔG stabilizing variations rather than the destabilizing ones. Here, we analyze the possible reasons for this difference by focusing on the relationship between experimentally-measured ΔΔG and seven protein properties on three widely-used datasets (S2648, VariBench, Ssym) and a recently introduced one (S669). These properties include protein structural information, different physical properties and statistical potentials. We found that two highly used input features, i.e., hydrophobicity and the Blosum62 substitution matrix, show a performance close to random choice when trying to separate stabilizing variants from either neutral or destabilizing ones. We then speculate that, since destabilizing variations are the most abundant class in the available datasets, the overall performance of the methods is higher when including features that improve the prediction for the destabilizing variants at the expense of the stabilizing ones. These findings highlight the need of designing predictive methods able to exploit also input features highly correlated with the stabilizing variants. New tools should also be tested on a not-artificially balanced dataset, reporting the performance on all the three classes (i.e., stabilizing, neutral and destabilizing variants) and not only the overall results

Protein Stability Perturbation Contributes to the Loss of Function in Haploinsufficient Genes

Missense variants are among the most studied genome modifications as disease biomarkers. It has been shown that the \u201cperturbation\u201d of the protein stability upon a missense variant (in terms of absolute \u394\u394G value, i.e., |\u394\u394G|) has a significant, but not predictive, correlation with the pathogenicity of that variant. However, here we show that this correlation becomes significantly amplified in haploinsufficient genes. Moreover, the enrichment of pathogenic variants increases at the increasing protein stability perturbation value. These findings suggest that protein stability perturbation might be considered as a potential cofactor in diseases associated with haploinsufficient genes reporting missense variants

Impact of monotherapy on HIV-1 reservoir, immune activation, and co-infection with Epstein-Barr virus

Abstract Objectives Although monotherapy (mART) effectiveness in maintaining viral suppression and CD4 cell count has been extensively examined in HIV-1-infected patients, its impact on HIV-1 reservoir, immune activation, microbial translocation and co-infection with Epstein-Barr Virus (EBV) is unclear. Methods This retrospective study involved 32 patients who switched to mART; patients were studied at baseline, 48 and 96 weeks after mART initiation. Thirty-two patients who continued combined antiretroviral therapy (cART) over the same period of time were included in the study. Markers of HIV-1 reservoir (HIV-1 DNA and intracellular HIV-1 RNA) were quantified by real-time PCR. Markers of T-(CD3(+)CD8(+)CD38(+)) and B-(CD19(+)CD80/86(+) and CD19(+)CD10-CD21(low)CD27(+)) cell activation were evaluated by flow cytometry. Plasma levels of microbial translocation markers were quantified by real-time PCR (16S ribosomal DNA and mitochondrial [mt] DNA) or by ELISA (LPS and sCD14). EBV was typed and quantified by multiplex real-time PCR. Results At baseline, no differences were found between mART and cART groups. Three (10%) mART-treated patients had a virological failure vs none in the cART group. Levels of HIV-1 DNA, intracellular HIV-1 RNA and EBV-DNA remained stable in the mART group, while decreased significantly in the cART group. Percentages of T-and B-activated cells significantly increased in the mART-treated patients, while remained at low levels in the cART-treated ones (p = 0.014 and p<0.001, respectively). Notably, levels of mtDNA remained stable in the cART group, but significantly rose in the mART one (p<0.001). Conclusions Long-term mART is associated with higher levels of T-and B-cell activation and, conversely to cART, does not reduce the size of HIV-1 reservoir and EBV co-infection

Asiakaslähtöisen munasolunsaajien hoitoprosessin kehittäminen lapsettomuusklinikalla

Tämä opinnäytetyö oli työelämä lähtöinen kehittämistyö, joka toteutettiin Väestöliiton lapsettomuus klinikoiden Helsingin yksikössä. Tämän kehittämistyön tarkoituksena oli tuottaa uusi asiakaslähtöinen munansolunsaajien hoitoprosessi ja sen myötä parantaa asiakkaiden tyytyväisyyttä saamaansa hoitoon. Kehittämishankkeen tavoitteena oli kartoittaa haastattelemalla munasolunluovutushoidon läpi käyneiden asiakkaiden näkemyksiä nykyisestä hoitoprosessista ja sen asiakaslähtöisyydestä. Tavoitteena oli myös huomioida klinikan kokeneen henkilökunnan ajatuksia hoitoprosessin parantamiseksi. Uuden hoitoprosessin luominen aloitettiin määrittelemällä nykyinen munasolunsaajien hoitoprosessi. Tämän jälkeen kartoitettiin munasolunluovutushoidon läpi käyneiden asiakkaiden näkemyksiä nykyisestä hoitoprosessista, sen asiakaslähtöisyydestä ja heidän ehdotuksia hoitoprosessin parantamiseksi. Analysoitujen haastattelu aineistojen avulla tehtiin hahmotelma uudesta hoitoprosessista. Hahmotelma hoitoprosessista ja haastatteluiden tulokset esiteltiin klinikan henkilökunnalle, joka ideoi näiden pohjalta kehittämiskohteita uuteen hoitoprosessiin. Edellisten vaiheiden jälkeen kehitettiin lopullinen versio uudesta hoitoprosessista. Munasolunluovutushoito on otettu käyttöön Väestöliiton klinikoilla vuonna 1991 ja se on nykyisin yksi standardi lapsettomuudenhoito menetelmä. Munasolunluovutushoito on saajille iso panostus henkisesti ja taloudellisesti. Hoitoprosessin kehittämisellä pyritään siihen, että hoitoprosessin toimimattomuuden takia he eivät joutuisi uusien pettymysten eteen. Terveydenhuollossa on ymmärretty viime vuosina asiakaslähtöisyyden tärkeys niin Suomessa, kuin maailmallakin. Opinnäytetyön lähestymistapana oli toimintatutkimus. Aineistonkeruu menetelmänä oli munasolunluovutushoidossa olleiden asiakkaiden teemahaastattelu. Tämän lisäksi henkilökunnan ehdotuksia hoitoprosessin kehittämiseksi kartoitettiin aivoriihi ideoinnin avulla. Teemahaastatteluun osallistui kahdeksan asiakasta ja haastatteluaineisto analysoitiin induktiivisella sisällön analyysilla. Aivoriihi ideoinnin tuloksena syntyneet ideat pisteytettiin, ryhmiteltiin ja yhdisteltiin samaa tarkoittaviin ideoihin. Tämän jälkeen aineistosta muodostettiin uusi hoitoprosessi. Haastatteluaineiston tulosten mukaan asiakaslähtöisyys on empaattista vuorovaikutusta ja asiakkaan kokonaisuuden huomioimista. Asiakkaat kokivat nykyisen hoitoprosessin sujuvana, mutta toisaalta kokivat siihen sisältyvän hallitsemattomuutta. Hyvänä nykyisessä hoitoprosessissa he kokivat tulosten mukaan olevan empaattisen ja yksilöllisen kohtaamisen ja hoitoprosessin yksilöllisyyden. Monipuolisiin palveluihin, hoitoprosessin yksilölliseen suunnitteluun ja psyykkiseen taakkaan tulisi tulosten mukaan kiinnittää huomiota uutta hoitoprosessia laadittaessa. Suomessa ei ole tehty tutkimuksia asiakaslähtöisyydestä lapsettomuushoitoihin liittyen. Ulkomaisista tutkimuksista on saatu samansuuntaisia tuloksia asiakaslähtöisyydestä lapsettomuushoitoihin liittyen kuin tässä opinnäytetyössä. Se osoittaa samojen asioiden olevan tärkeitä lapsettomuuspotilaille maan rajoista huolimatta. Jatkossa Väestöliiton klinikoilla tulisi tehdä seurantaa, siitä miten uuden hoitoprosessin käyttöönotto on mennyt.This thesis is the result of a workplace based development project implemented at the Väestöliitto fertility clinic in Helsinki. The goal of the project was to develop a new patient centred ovum donation process which would increase patients’ satisfaction with their care. The aim of the project was to survey thoughts of patients who had gone through the ovum donation process with regard to the current treatment process and its patient centeredness. The expertise of the more experienced employees of the clinic was to be taken into consideration throughout the development project. The development of the new process began by defining the current care process for ovum donation recipients. Following this, the ovum donation recipients were interviewed for their thoughts of the current care process and its patient centeredness. The patients were asked for suggestions for the improvement of the care process. Following an analysis of the intelligence gathered from the interviews, an outline for a new patient care process was drafted. The analysis of the intelligence and the new patient care process were presented to the clinic employees at a staff event. The goal of the event was to encourage the employees to brainstorm ideas for improving patient centeredness and thus enabling them to take part in developing the improved patient care process. Following the event, with the new ideas gathered, the final care process was developed. The ovum donation treatments started in 1991 at Väestöliitto fertility clinic and it is today one of the standard treatment methods for infertility. The treatment method requires a significant financial and psychological input from the recipients. The patients treated by this method have usually suffered from infertility for several years already, and have experienced many disappointments whilst going through previous infertility treatments. The aim of developing the new, improved patient care process, is that a poor design of the care process would not add to the disappointments that the patient may experience. The value of patient centeredness has been realised in Finland and all over the world in the recent years. The approach for this thesis was an action research method. The data was collected by interviewing patients and by executing a brainstorming event with the personnel. Eight patients who had undergone ovum donation were interviewed by an individual theme interview method. The data was analysed by inductive content analysis. The new ideas collected during the brainstorming ses-sion were categorised into groups based on their similarities and differences. By using a points system, the ideas and categories were analysed and the most significant ideas were utilized in the design of the new care process. The results of the patient interviews show that patient centeredness is empathic interaction and entire consideration of the patient. The patients felt that the current care process was fluent, but uncontrollable. Positive things in the current treatment process were empathic and individual encounter with the caregivers and the individuality of the treatment process. According to analysed data, a diverse range of treatment methods, individual planning of the treatment process, and the psychological burden of the treatments are things which should be taken carefully into account when planning new treatment processes. Previous studies show similar results about patient centerednes

Editorial: Computational and experimental protein variant interpretation in the era of precision medicine

Most traits of the human phenotype depend on the combination of various genetic factors with environmental influences, and a major challenge is the understanding of the relationship among genetic and phenotype variations (Casadio et al., 2011). In the last years, both advancements in human genome sequencing technologies and the creation of databases collecting information on human variations at the gene and protein levels have hugely enhanced the investigations on the role of these variations in determining health and disease (Austin-Tse et al., 2022). At the same time, the increasing amount of data generated by these resources are requiring new accurate and reliable computer-aided tools to predict phenotype–genotype associations (Brandes et al., 2023; Cheng et al., 2023). Efficient and powerful analytical methods are necessary for the discovery of unknown etiologies, which is important for rare diseases (Greene et al., 2023). Licata et al. highlighted the most relevant online resources and computational tools for single-nucleotide variant interpretation that can enhance the diagnosis, clinical management, and development of treatments for rare disorders

DataSheet1_Unravelling the instability of mutational signatures extraction via archetypal analysis.PDF

The high cosine similarity between some single-base substitution mutational signatures and their characteristic flat profiles could suggest the presence of overfitting and mathematical artefacts. The newest version (v3.3) of the signature database available in the Catalogue Of Somatic Mutations In Cancer (COSMIC) provides a collection of 79 mutational signatures, which has more than doubled with respect to previous version (30 profiles available in COSMIC signatures v2), making more critical the associations between signatures and specific mutagenic processes. This study both provides a systematic assessment of the de novo extraction task through simulation scenarios based on the latest version of the COSMIC signatures and highlights, through a novel approach using archetypal analysis, which COSMIC signatures are redundant and more likely to be considered as mathematical artefacts. 29 archetypes were able to reconstruct the profile of all the COSMIC signatures with cosine similarity >0.8. Interestingly, these archetypes tend to group similar original signatures sharing either the same aetiology or similar biological processes. We believe that these findings will be useful to encourage the development of new de novo extraction methods avoiding the redundancy of information among the signatures while preserving the biological interpretation.</p

HIV-1 reservoir levels in mART-treated and cART-treated patients.

<p>HIV-1 DNA (A) and intracellular HIV-1 RNA (B) levels in mART and cART patients at baseline, at 48 and 96 weeks of follow-up. Each symbol represents one patient. The lines indicate the median and the 25–75th percentiles.</p

Circulating markers of immune activation levels in mART-treated and cART-treated patients.

<p>mtDNA (A), 16S rDNA (B), sCD14 (C) and LPS (D) levels in mART and cART patients at baseline, at 48 and 96 weeks of follow-up. Each symbol represents one patient. The lines indicate the median and the 25–75th percentiles.</p