Store-operated Ca2+ entry (SOCE) channels are highly selective Ca2+ channels activated by the endoplasmic reticulum (ER) sensors STIM1 and STIM2. Their direct interaction with the pore-forming plasma membrane ORAI proteins (ORAI1, ORAI2, and ORAI3) leads to sustained Ca2+ fluxes that are critical for many cellular functions. Mutations in the human ORAI1 gene result in immunodeficiency, anhidrotic ectodermal dysplasia, and enamel defects. In our investigation of the role of ORAI proteins in enamel, we identified enamel defects in a patient with an ORAI1 null mutation. Targeted deletion of the Orai1 gene in mice showed enamel defects and reduced SOCE in isolated enamel cells. However, Orai2−/− mice showed normal enamel despite having increased SOCE in the enamel cells. Knockdown experiments in the enamel cell line LS8 suggested that ORAI2 and ORAI3 modulated ORAI1 function, with ORAI1 and ORAI2 being the main contributors to SOCE. ORAI1-deficient LS8 cells showed altered mitochondrial respiration with increased oxygen consumption rate and ATP, which was associated with altered redox status and enhanced ER Ca2+ uptake, likely due to S-glutathionylation of SERCA pumps. Our findings demonstrate an important role of ORAI1 in Ca2+ influx in enamel cells and establish a link between SOCE, mitochondrial function, and redox homeostasis.

Objective: Evaluate simulation-based comprehensive cleft care workshops as a reproducible model for education with sustained impact. Design: Cross-sectional survey-based evaluation. Setting: Simulation-based comprehensive cleft care workshop. Participants: Total of 180 participants. Interventions: Three-day simulation-based comprehensive cleft care workshop. Main Outcome Measures: Number of workshop participants stratified by specialty, satisfaction with the workshop, satisfaction with simulation-based workshops as educational tools, impact on cleft surgery procedural confidence, short-term impact on clinical practice, medium-term impact on clinical practice. Results: The workshop included 180 participants from 5 continents. The response rate was 54.5%, with participants reporting high satisfaction with all aspects of the workshop and with simulation-based workshops as educational tools. Participants reported a significant improvement in cleft lip (33.3 ± 5.7 vs 25.7 ± 7.6; P < .001) and palate (32.4 ± 7.1 vs 23.7 ± 6.6; P < .001) surgery procedural confidence following the simulation sessions. Participants also reported a positive short-term and medium-term impact on their clinical practices. Conclusion: Simulation-based comprehensive cleft care workshops are well received by participants, lead to improved cleft surgery procedural confidence, and have a sustained positive impact on participants’ clinical practices. Future efforts should focus on evaluating and quantifying this perceived positive impact, as well reproducing these efforts in other areas of need.

Objective: To present preliminary efforts to establish an internationally agreed set of minimum core practice and best practice guidelines, along with overarching principles to promote safe and comprehensive cleft care globally. Design: Representatives from 6 national and international organizations collaborated to form a World Cleft Coalition. Representatives met monthly/bimonthly to compile standards for safe, comprehensive, and sustainable cleft care. Outcomes were circulated within each organization and to a small subset of external constituents for feedback. Results: A series of overarching principles were established for those involved in International Cleft Treatment Programs, based on the experience of participating organizations. The overarching principles are followed by a structured and detailed Recommended Practice for Ensuring Safe, Comprehensive and Sustainable Cleft Care, which includes minimum core and best practice for the following areas: surgical safety, quality control, patient education, patient selection, patient follow-up, comprehensive care, partnership with the host nations and professionals, training and exchanges for sustainability, and local capacity building. Conclusions: Outcomes aimed to provide a working document to define core principles for safe comprehensive cleft care, while balancing various levels of resources, geographic locations, appropriately trained health care professional specialists, and training limitations. The study highlights the process and benefits to a collaborative international working group not only to establish best practice but also to solicit and engage others in discussion of their experiences with building and supporting safe, high-quality, comprehensive, sustainable, worldwide cleft care.