Efficient derivation of dopaminergic neurons from SOX1(-) floor plate cells under defined culture conditions.

BACKGROUND: Parkinson's disease (PD) is a severe neurodegenerative disease associated with loss of dopaminergic neurons. Derivation of dopaminergic neurons from human embryonic stem cells (hESCs) could provide new therapeutic options for PD therapy. Dopaminergic neurons are derived from SOX(-) floor plate (FP) cells during embryonic development in many species and in human cell culture in vitro. Early treatment with sonic hedgehog (Shh) has been reported to efficiently convert hESCs into FP lineages. METHODS: In this study, we attempted to utilize a Shh-free approach in deriving SOX1(-) FP cells from hESCs in vitro. Neuroectoderm conversion from hESCs was achieved with dual inhibition of the BMP4 (LDN193189) and TGF-β signaling pathways (SB431542) for 24 h under defined culture conditions. RESULTS: Following a further 5 days of treatment with LDN193189 or LDN193189 + SB431542, SOX1(-) FP cells constituted 70-80 % of the entire cell population. Upon treatment with Shh and FGF8, the SOX1(-) FP cells were efficiently converted to functional Nurr1(+) and TH(+) dopaminergic cells (patterning), which constituted more than 98 % of the entire cell population. However, when the same growth factors were applied to SOX1(+) cells, only less than 4 % of the cells became Nurr1(+), indicating that patterning was effective only if SOX1 expression was down-regulated. After transplanting the Nurr1(+) and TH(+) cells into a hemiparkinsonian rat model, significant improvements were observed in amphetamine induced ipslateral rotations, apomorphine induced contra-lateral rotations and Rota rod motor tests over a duration of 8 weeks. CONCLUSIONS: Our findings thus provide a convenient approach to FP development and functional dopaminergic neuron derivation.published_or_final_versio

Tooth autotransplantation: An umbrella review

Tooth autotransplantation is a versatile procedure with several clinical applications among patients across different age groups. The success of this procedure depends on multiple factors. Despite the wealth of studies available, no single primary study or systematic review is able to report on every factor affecting the outcomes of autotransplantation. The aims of this umbrella review were to evaluate treatment-related and patient-related outcomes of autotransplantation and to assess the pre-, peri- or post-operative factors that could affect these. An umbrella review was conducted according to the PRISMA statement. A literature search of five databases was performed up to 25 September 2022. Systematic Reviews (SR) with and without meta-analysis evaluating autotransplantation were included. Calibration among reviewers was carried out prior to study selection, data extraction and Risk of Bias (RoB) assessment. Study overlap was calculated using corrected covered area. Meta-meta-analysis (MMA) was performed for suitable SRs. The AMSTAR 2 critical appraisal tool was used to evaluate the quality of evidence. Seventeen SRs met the inclusion criteria. Only two SRs were suitable for conduct of MMA on autotransplantation of open apex teeth. The 5-year and 10-year survival rates were >95%. A narrative summary on factors that could affect autotransplantation outcomes and comparisons of autotransplantation to other treatment options were reported. Five SRs were rated as ‘low quality’ and 12 SRs were rated as ‘critically low quality’ in the AMSTAR 2 RoB assessment. In order to facilitate a more homogenous pool of data for subsequent meta-analysis, an Autotransplantation Outcome Index was also proposed to standardise the definition of outcomes. Autotransplantation of teeth with open apices have a high survival rate. Future studies should standardise the reporting of clinical and radiographic findings, as well as the definition of outcomes.Open Access funding provided by the Qatar National Library

The use of aesthetic paediatric full coverage restorations among paediatric dental practitioners: an international survey

Despite the recent growing evidence in support of prefabricated zirconia crown use as a successful option in managing grossly carious anterior and posterior primary teeth, the use of such crowns remains controversial within the paediatric dental profession. This study aims to assess the use of aesthetic full coverage paediatric restorations among paediatric dentists worldwide, with emphasis on aesthetic prefabricated zirconia crowns. This was an online cross-sectional survey questionnaire study comprising of 38 multiple-choice questions disseminated worldwide through the contact lists of national, regional and international paediatric dental organisations and social media platforms. The survey was completed by 556 respondents thus achieving power, with 391 (70.3%) females and 165 (29.7%) males. The respondents were from 55 different countries spread across six continents. The use of aesthetic full coverage restorations was reported by 80% (n = 444) of the respondents. For restoring anterior teeth, participants mainly used either composite strip crowns (94.4%, n = 419) or zirconia crowns (73.6%, n = 327), while those who used aesthetic crowns for restoring posterior teeth mainly used zirconia crowns (68.2%, n = 303). Within the limitations of this study, the results have shown a wide use of full coverage aesthetic restorations, including the use of zirconia crowns, of primary teeth within this international sample of practicing dentists.Scopu

Effect of dental trauma management resources on dental practitioners' confidence and knowledge: A pilot cross-sectional study

Background/Aim: The knowledge of standardized care guidelines is critical to the confidence of practitioners in managing dental trauma. Therefore, the aim of this study was to assess the awareness, use and impact of the International Association of Dental Traumatology guidelines, and the online Dental Trauma Guide on general dental practitioners' self-reported confidence and knowledge in managing traumatic dental injuries in the primary and permanent dentitions. Materials and Methods: A cross-sectional, pre-piloted, 27-item self-administered questionnaire survey was distributed electronically to general dental practitioners' working within five member states of the Gulf Cooperation Council countries (Kingdom of Bahrain, Kingdom of Saudi Arabia, Kuwait, Oman, and Qatar) between September and December 2020. Data were collected and analysed using descriptive statistics and Wilcoxon Signed Rank test analysis for relevant comparisons. Results: A total of 294 respondents completed the survey, with the majority being from the Kingdom of Saudi Arabia (47.4%) and Qatar (27.3%). A lack of evidence-based knowledge in managing traumatic dental injuries was evident among more than half of the respondents. Respondents who were cognizant of the recent International Association of Dental Traumatology guidelines (2020) and those who use the Dental Trauma Guide routinely demonstrated a higher self-reported confidence level in managing both simple and complex primary dentition trauma, as well as simple traumatic dental injuries in the permanent dentition (p <.05). Conclusion: This survey highlights critical deficiencies in the knowledge of a large number of the respondents in the management of dental trauma which is likely to cause irreversible long-term patient effects.Open Access funding provided by the Qatar National Library

Vital Pulp Therapy in Primary Teeth with Deep Caries: An Umbrella Review.

Purpose: The purpose of this umbrella review was to retrieve and assess the available systematic reviews reporting on pulp treatment of vital primary teeth with deep carious lesions. Methods: A literature search was conducted on electronic bibliographic databases to locate systematic reviews reporting on vital pulp therapy techniques or medicaments with two-arm comparisons and a follow-up period of at least 24 months. Eligible reviews were selected, data were extracted, and the risk of bias was assessed using a risk of bias in systematic reviews (ROBIS) tool. The degree of overlap was evaluated by calculating the corrected covered area (CCA). Results: Nine systematic reviews that cited 96 primary studies, with a high degree of overlap (14 percent CCA) were included. Indirect pulp capping had the highest success rate (94 percent) at 24 months, followed by direct pulp capping (88.8 percent), with different medicaments not significantly affecting the outcome. Pulpotomy showed the lowest success rate (82.6 percent), with the highest quality of evidence supporting the effective application of mineral trioxide aggregate (MTA) and formocresol (FC). Conclusions: The high success rate of pulp therapy techniques for the management of deep caries in vital primary teeth is evident; nevertheless, there remains insufficient evidence to draw scientifically solid conclusions about which technique and material are superior

Development of oral health resources and a mobile app for caregivers and autistic children through consensus building

This study aimed to (1) develop evidence-based resources and (2) test face, content validity, and usability of a newly developed mobile application (app) to equip and empower caregivers with resources and skills to promote better oral health for autistic children. A series of resources on oral health, including information on oral diseases and home care and social stories on dental visits were developed. Concurrently, an app was developed by dentists, occupational therapist and software developers. The resources underwent content validation by an international panel of paediatric dentists (Expert Working Group). Face validation of the resources and usability testing of the app by parents were then carried out. Validation and feedback were obtained by the Delphi method, with consensus set at 70% agreement. A total of 12 resources and 2 social stories were developed. Consensus was achieved among the Expert Working Group regarding the content and illustrations of the resources and social stories. Both the Expert Working Group and parents agreed that the resources were easy to read and understand. Parents also found the app easy to use, aesthetically pleasing and help them to better care for their child’s oral health. Lay Abstract: Caregivers of autistic children often lack knowledge regarding oral homecare and when and where to see the dentist. To address this need, we developed a series of information on oral health. An autistic child assisted in developing two social stories to showcase a dental visit. A mobile app was developed to deliver the above mentioned. Other features include creation of customised social stories and visual schedule and an inbox to allow dentists to send messages to parents. The developed information and social stories were reviewed by experts and parents. The app also underwent anonymous and independent testing by parents. Overall the information and app were well received by the experts and parents

Contemporary management of deep caries in primary teeth: a systematic review and meta-analysis.

PURPOSE To systematically evaluate the available evidence regarding contemporary management of deep caries in vital primary teeth. This review was carried out to facilitate the development of European Academy of Paediatric Dentistry (EAPD) guidelines on deep caries management of primary teeth in paediatric dentistry. METHODS A systematic electronic literature search was conducted to locate studies reporting on interventions and medicaments used for the treatment of deep caries in vital primary teeth. To facilitate this, the Cochrane Library (1992 to up to December 6th, 2020), MEDLINE (PubMed, 1946 to December Week 1, 2020), Ovid MEDLINE (In-Process & Other Non-Indexed Citations, December 6th, 2020); EMBASE (Embase.com, 1974 to December 6th, 2020) and LILACS (1982 to December 6th, 2020) were accessed. Hand search of reference lists of included articles, as well as handbooks and grey literature search was also performed. Study screening was done in duplicate and study inclusions were agreed upon by all authors. Data extraction, and methodological quality and risk of bias assessment were carried out in duplicate for each of the included studies. Overall success rate of each intervention and medicament within the intervention was reported. Meta-analysis was also performed for high-quality studies reporting similar interventions and comparable outcomes in homogeneous population. RESULTS A total of 1332 papers were identified. Following the primary and secondary assessment process, 36 papers were included in the review. Of these, 8 papers were deemed to represent 4 individual studies, leaving a total of 32 unique studies eventually included in the final analysis. These studies were further categorized into three main vital pulp treatment methods for analysis: indirect pulp capping (IPC), direct pulp capping (DPC), and pulpotomy (PP). Overall, IPC, DPC and PP interventions have high success rates with the reported clinical success rates higher than radiographic success rates. Medicaments used for IPC and DPC have similar success rates. Mineral trioxide aggregate (MTA), ferric sulfate (FS) and formocresol (FC) PP showed similar success rates, and which were all higher than calcium hydroxide (CH). Majority of included studies (n = 22; 63%) were rated low in terms of their potential risk of bias, 6 studies were rated high (17%), and 7 studies were of unclear risk (20%). CONCLUSION Within the limitations of the studies included, IPC, DPC, and PP can be recommended as effective treatment modalities for primary teeth with deep caries under specific conditions

Deep Dentine Caries Management of Immature Permanent Posterior Teeth with Vital Pulp: A Systematic Review and Meta-analysis.

OBJECTIVES Preservation of pulpal vitality in immature permanent teeth with deep carious lesions is essential to enable further root development and apical closure. This systematic review aimed to evaluate the evidence regarding the efficacy, presented clinical and radiographic success, and bacteriological outcomes of techniques and materials used for deep caries management in vital immature permanent teeth. DATA Randomised controlled trials evaluating Vital Pulp Therapy (VPT) for deep caries in immature permanent posterior teeth without history of irreversible pulpitis, and a follow up period of ≥12 months were included. Study characteristics and outcomes of all included studies were summarized. Cochrane's Risk-of-bias tool 2.0 was used to assess the quality of eligible studies. Meta-analyses using a random effects model was performed. SOURCES Electronic databases PubMed, Medline, Embase, LILACS, CENTRAL and Cochrane Library were searched, followed by a manual search. STUDY SELECTION Twelve papers were included into the review. Overall success rates were 98%, 93.5%, 93.6% for direct pulp cap (DPC), indirect pulp cap (IPC) and pulpotomy (PP) respectively. Regardless of VPT technique, there were no significant differences between clinical and radiographic success rates. Completion of root development was achieved in more than 83% of the cases in all VPT techniques. CONCLUSIONS All treatment modalities for PP were equally efficient with high overall success rates. Biodentine showed high success rates regardless of technique. No significant differences were found in the clinical and radiographic success rates between various follow-up intervals. There are no clear conclusions regarding superiority of either VPT technique on apical closure. CLINICAL SIGNIFICANCE This manuscript systematically evaluates the evidence and summarises all available data on each vital pulp therapy technique and materials used in treatment of deep caries in immature permanent teeth with vital pulps. The limitations in the current scientific literature and recommendations for future research are also highlighted

Deep dentine caries management of immature permanent posterior teeth with vital pulp: A systematic review and meta-analysis

Objectives: Preservation of pulpal vitality in immature permanent teeth with deep carious lesions is essential to enable further root development and apical closure. This systematic review aimed to evaluate the evidence regarding the efficacy, presented clinical and radiographic success, and bacteriological outcomes of techniques and materials used for deep caries management in vital immature permanent teeth. Data: Randomised controlled trials evaluating Vital Pulp Therapy (VPT) for deep caries in immature permanent posterior teeth without history of irreversible pulpitis, and a follow up period of ?12 months were included. Study characteristics and outcomes of all included studies were summarized. Cochrane's Risk-of-bias tool 2.0 was used to assess the quality of eligible studies. Meta-analyses using a random effects model was performed. Sources: Electronic databases PubMed, Medline, Embase, LILACS, CENTRAL and Cochrane Library were searched, followed by a manual search. Study Selection: Twelve papers were included into the review. Overall success rates were 98%, 93.5%, 93.6% for direct pulp cap (DPC), indirect pulp cap (IPC) and pulpotomy (PP) respectively. Regardless of VPT technique, there were no significant differences between clinical and radiographic success rates. Completion of root development was achieved in more than 83% of the cases in all VPT techniques. Conclusions: All treatment modalities for PP were equally efficient with high overall success rates. Biodentine showed high success rates regardless of technique. No significant differences were found in the clinical and radiographic success rates between various follow-up intervals. There are no clear conclusions regarding superiority of either VPT technique on apical closure. Clinical significance: This manuscript systematically evaluates the evidence and summarises all available data on each vital pulp therapy technique and materials used in treatment of deep caries in immature permanent teeth with vital pulps. The limitations in the current scientific literature and recommendations for future research are also highlighted. 2022The authors wish to thank all the corresponding authors of the studies who assisted us with our clarifications on queries regarding their studies.Scopu