Sustainable Cleft Care: A Comprehensive Model Based on the Global Smile Foundation Experience

Introduction:Clefts of the lip and palate are leading congenital facial anomalies. Underserved patients with these facial differences lack access to medical care, surgical expertise, prenatal care, or psychological support. Moreover, the disease results in significant economic strains on patients and their families. While surgical outreach programs have attempted to fill this void, significant challenges facing international comprehensive cleft care persist.Objective:Propose a path toward international sustainable cleft care based on the Global Smile Foundation experience.Results:International sustainable comprehensive cleft care can be achieved by regulating surgical outreach programs. Regulation of these missions would ensure standardized care and encourage stakeholders to cooperate and adequately allocate funding and resources. Capacity building can be achieved through “diagonal” cleft care delivery models, multidisciplinary workshops, fellowship programs, research and quality assurance, as well as leveraging emerging technologies such as Augmented Reality.Conclusion:International comprehensive cleft care requires continuous collaborative efforts between visiting and local teams as well as international and national organizations. Standardizing and regulating current practices as well as promoting capacity building initiatives can contribute to sustainable cleft care.</jats:sec

BTP-7, a novel peptide for therapeutic targeting of malignant brain tumors

AbstractBackgroundTargeted therapies for malignant brain cancer that are currently available have little clinical activity, highlighting an urgent need for the development of novel precision medicines. Brevican (Bcan), a central nervous system (CNS)-specific extracellular matrix protein is upregulated in glioma cells. A brevican isoform lacking glycosylation, dg-Bcan, is a unique glioma marker and thus represents a valuable target for anti-cancer therapy. In this study, we aimed to find a versatile dg-Bcan specific ligand to facilitate glioma targeting.MethodsWe screened a D-peptide library to identify dg-Bcan-Targeting Peptide (BTP) candidates, which were characterized extensively through binding kinetic analyses, cell uptake tests and animal studies.ResultsThe top candidate, BTP-7 binds dg-Bcan with high affinity and specificity, is preferentially internalized by Bcan-expressing glioma cells and can cross the blood-brain barrier in vitro and in mice. Functionalization of camptothecin with BTP-7 led to increased drug delivery to intracranial glioblastoma and cytotoxicity in tumor tissues, as well as prolonged survival in tumor-bearing mice.Conclusiondg-Bcan is an attractive therapeutic target for high-grade gliomas, and BTP-7 represents a promising lead candidate for further development into novel targeted therapeutics.Key pointsBTP-7 is a high affinity peptide ligand for the dg-Bcan protein and Bcan-expressing cells.BTP-7 targets human intracranial GBM xenografts in mice.Functionalization of a toxic anti-cancer drug with BTP-7 enables targeted delivery of the therapeutic to intracranial GBM in miceImportance of the StudyTargeted therapies for malignant brain cancer that are currently available have little clinical activity, highlighting an urgent need for the development of novel precision medicines that can selectively recognize and kill high-grade glioma tissues. A protein called dg-Bcan is an ideal target because it is present only in the extracellular matrix of high-grade glioma cells and is absent from normal brain tissues. Here, we describe the discovery of a novel dg-Bcan-Targeting Peptide, called BTP-7 that can bind specifically to high-grade glioma cells/tissues, and thus serve as a promising drug delivery vehicle.</jats:sec

Targeting Glioblastoma Using a Novel Peptide Specific to a Deglycosylated Isoform of Brevican

Glioblastoma (GBM) is the most common and deadliest form of brain tumor and remains amongst the most difficult cancers to treat. Brevican (Bcan), a central nervous system (CNS)-specific extracellular matrix protein, is upregulated in high-grade glioma cells, including GBM. A Bcan isoform lacking most glycosylation, dg-Bcan, is found only in GBM tissues. Here, dg-Bcan is explored as a molecular target for GBM. In this study, a d-peptide library is screened to identify a small 8-amino acid dg-Bcan-Targeting Peptide (BTP) candidate, called BTP-7 that binds dg-Bcan with high affinity and specificity. BTP-7 is preferentially internalized by dg-Bcan-expressing patient-derived GBM cells. To demonstrate GBM targeting, BTP-7 is radiolabeled with 18F, a radioisotope of fluorine, and increased radiotracer accumulation is found in intracranial GBM established in mice using positron emission tomography (PET) imaging. dg-Bcan is an attractive molecular target for GBM, and BTP-7 represents a promising lead candidate for further development into novel imaging agents and targeted therapeutics

Simulation-Based Comprehensive Cleft Care Workshops: A Reproducible Model for Sustainable Education

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