The Secreted Metalloprotease ADAMTS20 Is Required for Melanoblast Survival

ADAMTS20 (A disintegrin-like and metalloprotease domain with thrombospondin type-1 motifs) is a member of a family of secreted metalloproteases that can process a variety of extracellular matrix (ECM) components and secreted molecules. Adamts20 mutations in belted (bt) mice cause white spotting of the dorsal and ventral torso, indicative of defective neural crest (NC)-derived melanoblast development. The expression pattern of Adamts20 in dermal mesenchymal cells adjacent to migrating melanoblasts led us to initially propose that Adamts20 regulated melanoblast migration. However, using a Dct-LacZ transgene to track melanoblast development, we determined that melanoblasts were distributed normally in whole mount E12.5 bt/bt embryos, but were specifically reduced in the trunk of E13.5 bt/bt embryos due to a seven-fold higher rate of apoptosis. The melanoblast defect was exacerbated in newborn skin and embryos from bt/bt animals that were also haploinsufficient for Adamts9, a close homolog of Adamts20, indicating that these metalloproteases functionally overlap in melanoblast development. We identified two potential mechanisms by which Adamts20 may regulate melanoblast survival. First, skin explant cultures demonstrated that Adamts20 was required for melanoblasts to respond to soluble Kit ligand (sKitl). In support of this requirement, bt/bt;Kittm1Alf/+ and bt/bt;KitlSl/+ mice exhibited synergistically increased spotting. Second, ADAMTS20 cleaved the aggregating proteoglycan versican in vitro and was necessary for versican processing in vivo, raising the possibility that versican can participate in melanoblast development. These findings reveal previously unrecognized roles for Adamts proteases in cell survival and in mediating Kit signaling during melanoblast colonization of the skin. Our results have implications not only for understanding mechanisms of NC-derived melanoblast development but also provide insights on novel biological functions of secreted metalloproteases

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Reconstruction of Severely Resorbed Maxilla with Biodegradable Polylactide Screws: Case Series

Purpose: After the loss of natural teeth, bone changes in the jaws begin to take place immediately. Because the alveolar bone no longer responds to stresses placed in this area by teeth and periodontal ligaments, the bone begins to resorb. In such cases, alveolar bone reconstruction followed by implant-prosthetic treatment must be considered to reestablish esthetics and function. The present study was designed to compare and evaluate the effectiveness of titanium screws and absorbable fixation systems for the fixation of autogenous onlay bone grafts in maxillary reconstruction. Materials and Methods: A total of 10 consecutive patients with severely resorbed maxillae were referred to the Oral and Maxillofacial Surgery Department at Piracicaba Dental School, Campinas State University (Sao Paulo, Brazil), for oral rehabilitation through implant placement. The bone defects were treated by autologous bone grafting from the iliac crest, which was fixed with absorbable screws. The patients were followed for a minimum of 6 months after prosthodontic work was concluded. Results: The average age of the patients in this study was 46.9 years. Two dental implants were lost during the healing period. Four absorbable screws showed an unusual tissue reaction and were lost, and 90% of patients received the planned fixed prostheses. The implant success rate was 97% at 1 year after prosthesis placement. Conclusion: Fixation with absorbable screws has been shown to be safe and predictable. The absorbable screws did not interfere with bone graft healing and dental implant osseointegration. INT J ORAL MAXILLOFAC IMPLANTS 2010;25:821-82525482182

Mineralized Tissue Formation Associated With 2 Different Dental Implant Designs: Histomorphometric Analyses Performed in Dogs

The clinical success of dental implants might be associated with such factors as installation technique, implant shape, size, material, and screw threads. Therefore, the aim of this study is to analyze mineralized tissue formation on the screw threads of conical and cylindrical dental implants. This study includes 7 beagle dogs that had the lower premolars extracted. Three months after bone and soft tissue repair, 2 different designs of dental implants (1 conical and 1 cylindrical) were installed in each hemimandible using a nonsubmerged technique. Both implants when installed had different shape and thread, as revealed by scanning electron microscopy. Six weeks after implant installation, animals were killed and submitted to histomorphometric analysis. Cervical, middle, and apical areas were analyzed. Statistical analysis was carried out using Student t test at a significance level of P < .05. Statistically significant differences were not found between the conical and cylindrical implants. The conical implants presented fewer threads, a smaller area, and more bone formation when compared with the cylindrical ones, without significant differences (P = .1226). The highest values concerning bone formation were observed for the cervical area (P = .4005), and the lowest for the apical area (P = .1899); however, no statistically significant difference was observed. In conclusion, no statistically significant difference was observed in thread bone formation between the cylindrical and conical implant designs when placed using the nonsubmerged technique.37331932

A Comparison of Motorcycle and Bicycle Accidents in Oral and Maxillofacial Trauma

Purpose: The aim of this study was to present a large series of motorcycle- and bicycle-related traumas to the face in an attempt to identify the injury pattern in motorcyclists and bicyclists. Patients and Methods: Data were collected from patients during a 10-year period (1999 through 2009), which included demographic data, diagnosis of facial fractures, use of protective devices, dentoalveolar trauma, and facial soft tissue injuries. Results: There were 556 patients with bicycle accidents and 367 with motorcycle accidents. Men were involved in 79% (436) of bicycles accidents and 82% (299) of motorcycle accidents. Young male patients were more frequent in bicycle and motorcycle accidents. Two hundred fifty bicyclists showed 311 maxillofacial fractures. Two hundred twenty-one motorcyclists showed 338 maxillofacial fractures. Motorcycle accidents caused multiple fractures in more patients. Seventy-six percent of motorcyclists were using helmets at the time of the accidents, whereas 6% of cyclists were using helmets. Motorcyclists showed a larger number of lacerations, whereas bicyclists showed a larger number of abrasions. Avulsion was the most common dentoalveolar injury for these accident types. Hospital stays were 3.8 days for motorcyclists and 1.3 days for bicyclists. Conclusions: The high-impact collisions typically observed in motorcycle accidents is directly related to larger percentages of soft tissue lacerations and facial fractures. The low-impact trauma that is observed in bicycle accidents is more commonly associated with soft tissue abrasion, hematoma, and dentoalveolar fractures. This stresses the need for compulsory legislation for helmet use with face-guards for cyclists and motorcyclists. It is important to take measures to alert the public regarding the severity of injuries likely to occur in bicycle- and motorcycle-related accidents and ways to prevent them. (c) 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70:577-583, 201270357758

Bone Repair is Influenced by Different Particle Sizes of Anorganic Bovine Bone Matrix: A Histologic and Radiographic Study In Vivo

Purpose: The aim of this study was to analyze histologically and radiographically the influence of particle size of anorganic bovine bone matrix (ABBM) on bone repair. Materials and Methods: Four calvarial defects of 8 mm each were prepared in 18 adult New Zealand rabbits. The defects were then filled with either particulate autogenous bone (control group) or ABBM of large, medium, and small size granules. The animals were sacrificed at 15, 30, and 60 days after surgery. The samples were radiographically examined before being submitted to histological processing. Results: Autogenous bone showed a slight radiopacity at the beginning, which was increased at the final period, being very similar to the adjacent bone tissue. The large and medium size ABBM particles maintained the same radiographic behavior, showing a radiolucent area in the central portion of the defect at 60 days. ABBM of small size granules showed a slight radiolucity at the initial period, which was increased at the subsequent periods. More intense bone formation occurred in the control group (autogenous bone). All 3 particle sizes of the biomaterial resulted in inflammatory infiltration at 15 and 30 days. ABBM of small size granules lead to a greater amount of osteoid tissue, and the particles were almost totally reabsorbed within 60 days of implantation. Conclusions: Autogenous bone graft lead to the best result in terms of bone defect repair; ABBM of large and medium size granules are not totally reabsorbed at the observed period; ABBM of small size granules was more intensively reabsorbed and led to a greater osteoid tissue formation when compared to the medium and large ABBM granules.24410741077Campinas States University, Piracicaba School of Dentistr

Incidence of Maxillary Sinusitis Following Le Fort I Osteotomy: Clinical, Radiographic, and Endoscopic Study

Purpose: The correction of maxillomandibular deformities may require maxillary osteotomy procedures that usually present low rates of postoperative complications, such as maxillary sinusitis. The present study evaluated the incidence of maxillary sinusitis after Le Fort I osteotomy in 21 adult patients who underwent maxillary surgery (Le Fort I osteotomy) or bimaxillary surgery (Le Fort I osteotomy plus sagittal mandibular osteotomies) for correction of dentofacial deformities. Patients and Methods: Verification of the presence of maxillary sinusitis was assessed through a brief questionnaire, x-rays (Waters views), and nasal endoscopy before surgery and 6 to 8 months after surgery. Results: Analysis of results showed an incidence of 4.76% of maxillary sinusitis as a postoperative complication in the studied population. Conclusion: Symptomatic patients with a positive radiographic finding or an increased risk for postoperative sinusitis will benefit from endoscopic evaluation to aid in treatment planning and follow-up. 0 2011 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 69:346351, 201169234635