Adapting Elements of Cleft Care Protocols in Low- and Middle-income Countries During and After COVID-19: A Process-driven Review With Recommendations.

A consortium of global cleft professionals, predominantly from low- and middle-income countries, identified adaptations to cleft care protocols during and after COVID-19 as a priority learning area of need.A multidisciplinary international working group met on a videoconferencing platform in a multi-staged process to make consensus recommendations for adaptations to cleft protocols within resource-constrained settings. Feedback was sought from a roundtable discussion forum and global organizations involved in comprehensive cleft care.Foundational principles were agreed to enable recommendations to be globally relevant and two areas of focus within the specified topic were identified. First the safety aspects of cleft surgery protocols were scrutinized and COVID-19 adaptations, specifically in the pre- and perioperative periods, were highlighted. Second, surgical procedures and cleft care services were prioritized according to their relationship to functional outcomes and time-sensitivity. The surgical procedures assigned the highest priority were emergent interventions for breathing and nutritional requirements and primary palatoplasty. The cleft care services assigned the highest priority were new-born assessments, pediatric support for children with syndromes, management of acute dental or auditory infections and speech pathology intervention.A collaborative, interdisciplinary and international working group delivered consensus recommendations to assist with the provision of cleft care in low- and middle-income countries. At a time of global cleft care delays due to COVID-19, a united approach amongst global cleft care providers will be advantageous to advocate for children born with cleft lip and palate in resource-constrained settings.

Use of Pig as a Model for Mesenchymal Stem Cell Therapies for Bone Regeneration.

Bone is a plastic tissue with a large healing capability. However, extensive bone loss due to disease or trauma requires extreme therapy such as bone grafting or tissue-engineering applications. Presently, bone grafting is the gold standard for bone repair, but presents serious limitations including donor site morbidity, rejection, and limited tissue regeneration. The use of stem cells appears to be a means to overcome such limitations. Bone marrow mesenchymal stem cells (BMSC) have been the choice thus far for stem cell therapy for bone regeneration. However, adipose-derived stem cells (ASC) have similar immunophenotype, morphology, multilineage potential, and transcriptome compared to BMSC, and both types have demonstrated extensive osteogenic capacity both in vitro and in vivo in several species. The use of scaffolds in combination with stem cells and growth factors provides a valuable tool for guided bone regeneration, especially for complex anatomic defects. Before translation to human medicine, regenerative strategies must be developed in animal models to improve effectiveness and efficiency. The pig presents as a useful model due to similar macro- and microanatomy and favorable logistics of use. This review examines data that provides strong support for the clinical translation of the pig model for bone regeneration.

Adipose-derived mesenchymal stem cells enhance healing of mandibular defects in the ramus of swine.

PURPOSE: This study investigated the effect of adipose-derived mesenchymal stem cells (ASCs) injected locally or systemically on the bone regeneration of a 10-mm-diameter cylindrical noncritical-size defect in the ramus of the pig mandible. MATERIALS AND METHODS: Fifteen Yorkshire pigs, weighing 60 to 80 kg, received bilateral 10-mm-diameter cylindrical surgical defects in each ramus of the mandible. Pigs received 1) a direct injection into the defect of 2.5 million carboxy-fluorescein diacetate succinimidyl ester-labeled ASCs from 1 of 2 pig donors (n = 6); 2) an ear vein injection of 5 million carboxy-fluorescein diacetate succinimidyl ester-labeled ASCs from 1 of 2 pig donors (n = 6); or 3) an ear vein injection of culture Dulbecco's Modified Eagle's Medium without stem cells (control; n = 3). Pigs from each treatment were sacrificed at 1 hour, 2 weeks, or 4 weeks after surgery. Healing of the defect was evaluated by dual-energy x-ray absorptiometry, micro-computed tomography, fluorescent microscopy, and histology. RESULTS: Bone healing was accelerated in the ASC-injected treatment groups at 2 and 4 weeks after surgery compared with the control pigs. CONCLUSIONS: Results from this animal model provide evidence that the injection of ASC locally into a bone defect or systemically can accelerate the healing of bone.

Craniometric and velopharyngeal assessment of infants with and without cleft palate.

BACKGROUND: The current study was designed to obtain qualitative and quantitative information of the velopharyngeal mechanism and craniometric dimensions in infants born with a normal mechanism and in infants with an unrepaired cleft palate. MATERIALS AND METHODS: Clinical magnetic resonance imaging data were obtained from the medical charts of 4 infants (2 with cleft lip and palate and 2 without) between the ages of 8 and 9 months. Craniometric measures and levator veli palatini muscle morphology were analyzed using visualization modeling software. Both raw measures and measures normalized by head circumference were examined. RESULTS: Patients 1 and 2 demonstrated normal velopharyngeal anatomy and a similar distance between levator muscle origins (38.9-40.7 mm), sagittal angles of origin (56-57 degrees), and levator muscle bundle lengths (28.4-30.7 mm). Patients with an unrepaired cleft palate displayed smaller oblique coronal angles of origins (58-62 degrees) compared with patients without cleft palate (62-67 degrees). Patients without cleft palate showed a steeper muscle (56-57 degrees) compared with patients without cleft palate (66-67 degrees). The basion-sella-nasion angle, hard palate length, and hard palate width measurements are related systematically to head circumference in this patient group. DISCUSSION: Results from the current study are in agreement with previous studies demonstrating variations across patients with cleft palate particularly in the muscle bundle lengths, distance between muscle origins, velar thickness, and velar length. Longitudinal studies are needed to determine how levator muscle and craniometric dimensions vary between those with and without cleft palate. A larger sample size is necessary to provide statistical analysis.

MRI and 3D Computer Modeling of the Levator Veli Palatini Muscle Before and After Primary Palatoplasty.

Abstract Objective: This study was designed for two purposes: (a) to obtain qualitative and quantitative information of the velopharyngeal mechanism in infants born with cleft palate before and after primary palatoplasty using MRI and 3D computer technology and (b) to demonstrate the potential of using computer technology and MRI for presurgical planning. Methods: Clinical MRI data were obtained from the medical charts of four infants (two with cleft lip and palate and two without) between 8 - 15 months of age. Computer technology was used to obtain quantitative measures of the levator veli palatini (levator) muscle and to create 3D computer models. Results: There was little difference in angles of origin between individuals with normal velopharyngeal anatomy (ranging from 41 masculine-45 masculine). Subjects with cleft palate displayed smaller angles of origins (average of 40 masculine) prior to surgery compared to that of the subjects without cleft palate (average of 43 masculine). Following surgery, the levator muscle increased in length (ranging from 32mm-40.4mm) and formed larger angles of origin (average of 39 masculine) becoming more similar to the angles of origin observed in the subjects without cleft palate. Conclusions: Although the subjects with normal anatomy displayed levator muscle lengths, thickness, and distance between origins that were dissimilar, nevertheless the angles of origin measures were similar. Subjects with cleft palate had greater variations in the angle of origin. It is possible that the angle of the muscle as it descends from the base of the skull might be a critical feature to produce velopharyngeal closure.

Identifying conserved gene clusters in the presence of homology families.

The study of conserved gene clusters is important for understanding the forces behind genome organization and evolution, as well as the function of individual genes or gene groups. In this paper, we present a new model and algorithm for identifying conserved gene clusters from pairwise genome comparison. This generalizes a recent model called "gene teams." A gene team is a set of genes that appear homologously in two or more species, possibly in a different order yet with the distance of adjacent genes in the team for each chromosome always no more than a certain threshold. We remove the constraint in the original model that each gene must have a unique occurrence in each chromosome and thus allow the analysis on complex prokaryotic or eukaryotic genomes with extensive paralogs. Our algorithm analyzes a pair of chromosomes in O(mn) time and uses O(m+n) space, where m and n are the number of genes in the respective chromosomes. We demonstrate the utility of our methods by studying two bacterial genomes, E. coli K-12 and B. subtilis. Many of the teams identified by our algorithm correlate with documented E. coli operons, while several others match predicted operons, previously suggested by computational techniques. Our implementation and data are publicly available at euler.slu.edu/ approximately goldwasser/homologyteams/.

Surgical management of facial skin cancer.

Surgical excision is the gold standard for management of cutaneous basal cell carcinoma or squamous cell carcinoma. Surgical management of nonmelanotic facial skin cancer requires preoperative planning and an in-depth understanding of reconstructive techniques, including primary closure, skin grafting, and local tissue flaps. The decision regarding the method of treatment of nonmelanotic skin cancer is highly individualized and depends on patient age, cancer size, histologic subtype, and site. No single therapy or technique can be used in every situation. The goals of treatment include complete removal of the lesion with preservation of normal tissue, function, and cosmesis. In this article we discuss the principles and techniques of surgical excision and reconstruction of site-specific facial skin cancers.

Magnetic resonance imaging of the levator veli palatini muscle before and after primary palatoplasty.

OBJECTIVE: To explore the application of magnetic resonance imaging (MRI) in the evaluation of patients with cleft palate before and after primary palatoplasty with particular attention focused on the levator veli palatini muscle. DESIGN: Prospective study using MRIs of subjects before and after primary cleft palate surgery. SETTING: Hospital and university based. PATIENTS: One female infant with normal anatomy. Three male and four female infants with cleft palate of varying severity. INTERVENTION: Furlow double-opposing Z-plasty and V-Y palatoplasty. MAIN OUTCOME MEASURES: Magnetic resonance images. RESULTS: It was found that the levator veli palatini muscle can be imaged before and after palatal surgery in infants using MRI. The muscle may have sufficient volume, proportionate to a normal infant or adult, in infants born with cleft palate. If retrodisplaced properly, the muscle is likely to be steeper (more vertical) from its origin at the base of the skull to its insertion into the velum following palatoplasty, thus providing a more favorable angle for elevating the velum. Following palatal surgery, the levator muscle mass may not be as cohesive across the velar midline, compared with normal musculature. CONCLUSION: MRI is a viable imaging modality for the evaluation of the anatomy of the levator veli palatini muscle before and after primary palatoplasty in infants born with cleft palate.