Complimentary vertebrate Wac models exhibit phenotypes relevant to DeSanto-Shinawi Syndrome.

Monogenic syndromes are associated with neurodevelopmental changes that result in cognitive impairments, neurobehavioral phenotypes including autism and attention deficit hyperactivity disorder (ADHD), and seizures. Limited studies and resources are available to make meaningful headway into the underlying molecular mechanisms that result in these symptoms. One such example is DeSanto-Shinawi Syndrome (DESSH), a rare disorder caused by pathogenic variants in the WAC gene. Individuals with DESSH syndrome exhibit a recognizable craniofacial gestalt, developmental delay/intellectual disability, neurobehavioral symptoms that include autism, ADHD, behavioral difficulties and seizures. However, no thorough studies from a vertebrate model exist to understand how these changes occur. To overcome this, we developed both murine and zebrafish Wac/wac deletion mutants and studied whether their phenotypes recapitulate those described in individuals with DESSH syndrome. We show that the two Wac models exhibit craniofacial and behavioral changes, reminiscent of abnormalities found in DESSH syndrome. In addition, each model revealed impacts to GABAergic neurons and further studies showed that the mouse mutants are susceptible to seizures, changes in brain volumes that are different between sexes and relevant behaviors. Finally, we uncovered transcriptional impacts of Wac loss of function that will pave the way for future molecular studies into DESSH. These studies begin to uncover some biological underpinnings of DESSH syndrome and elucidate the biology of Wac, with advantages in each model.

Lineage-specific mutation of Lmx1b provides new insights into distinct regulation of suture development in different areas of the calvaria.

The calvaria (top part of the skull) is made of pieces of bone as well as multiple soft tissue joints called sutures. The latter is crucial to the growth and morphogenesis of the skull, and thus a loss of calvarial sutures can lead to severe congenital defects in humans. During embryogenesis, the calvaria develops from the cranial mesenchyme covering the brain, which contains cells originating from the neural crest and the mesoderm. While the mechanism that patterns the cranial mesenchyme into bone and sutures is not well understood, function of Lmx1b, a gene encoding a LIM-domain homeodomain transcription factor, plays a key role in this process. In the current study, we investigated a difference in the function of Lmx1b in different parts of the calvaria using neural crest-specific and mesoderm-specific Lmx1b mutants. We found that Lmx1b was obligatory for development of the interfrontal suture and the anterior fontanel along the dorsal midline of the skull, but not for the posterior fontanel over the midbrain. Also, Lmx1b mutation in the neural crest-derived mesenchyme, but not the mesoderm-derived mesenchyme, had a non-cell autonomous effect on coronal suture development. Furthermore, overexpression of Lmx1b in the neural crest lineage had different effects on the position of the coronal suture on the apical part and the basal part. Other unexpected phenotypes of Lmx1b mutants led to an additional finding that the coronal suture and the sagittal suture are of dual embryonic origin. Together, our data reveal a remarkable level of regional specificity in regulation of calvarial development.

Employing Indirect Adenosine 2A Receptors (A2AR) to Enhance Osseointegration of Titanium Devices: A Pre-Clinical Study.

The present study aimed to evaluate the effect of dipyridamole, an indirect adenosine 2A receptors (A2AR), on the osseointegration of titanium implants in a large, translational pre-clinical model. Sixty tapered, acid-etched titanium implants, treated with four different coatings ((i) Type I Bovine Collagen (control), (ii) 10 µM dipyridamole (DIPY), (iii) 100 µM DIPY, and (iv) 1000 µM DIPY), were inserted in the vertebral bodies of 15 female sheep (weight ~65 kg). Qualitative and quantitative analysis were performed after 3, 6, and 12 weeks in vivo to assess histological features, and percentages of bone-to-implant contact (%BIC) and bone area fraction occupancy (%BAFO). Data was analyzed using a general linear mixed model analysis with time in vivo and coating as fixed factors. Histomorphometric analysis after 3 weeks in vivo revealed higher BIC for DIPY coated implant groups (10 µM (30.42% ± 10.62), 100 µM (36.41% ± 10.62), and 1000 µM (32.46% ± 10.62)) in comparison to the control group (17.99% ± 5.82). Further, significantly higher BAFO was observed for implants augmented with 1000 µM of DIPY (43.84% ± 9.97) compared to the control group (31.89% ± 5.46). At 6 and 12 weeks, no significant differences were observed among groups. Histological analysis evidenced similar osseointegration features and an intramembranous-type healing pattern for all groups. Qualitative observation corroborated the increased presence of woven bone formation in intimate contact with the surface of the implant and within the threads at 3 weeks with increased concentrations of DIPY. Coating the implant surface with dipyridamole yielded a favorable effect with regard to BIC and BAFO at 3 weeks in vivo. These findings suggest a positive effect of DIPY on the early stages of osseointegration.

3D printed mesoporous bioactive glass, bioglass 45S5, and ß-TCP scaffolds for regenerative medicine: A comparative in vitro study.

BACKGROUND: While autografts to date remain the "gold standard" for bone void fillers, synthetic bone grafts have garnered attention due to their favorable advantages such as ability to be tailored in terms of their physical and chemical properties. Bioactive glass (BG), an inorganic material, has the capacity to form a strong bond with bone by forming a bone-like apatite surface, enhancing osteogenesis. Coupled with additive manufacturing (3D printing) it is possible to maximize bone regenerative properties of the BG. OBJECTIVE: The objective of this study was to synthesize and characterize 3D printed mesoporous bioactive glass (MBG), BG 45S5, and compare to ß-Tricalcium phosphate (ß-TCP) based scaffolds; test cell viability and osteogenic differentiation on human osteoprogenitor cells in vitro. METHODS: MBG, BG 45S5, and ß-TCP were fabricated into colloidal gel suspensions, tested with a rheometer, and manufactured into scaffolds using a 3D direct-write micro-printer. The materials were characterized in terms of microstructure and composition with Thermogravimetric Analyzer/Differential Scanning Calorimeter (TGA/DSC), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Micro-Computed Tomography (µ-CT), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDS), and Mattauch-Herzog-Inductively Coupled Plasma-Mass Spectrometry (MH-ICP-MS). RESULTS: Scaffolds were tested for cell proliferation and osteogenic differentiation using human osteoprogenitor cells. Osteogenic media was used for differentiation, and immunocytochemistry for osteogenic markers Runx-2, Collagen-I, and Osteocalcin. The cell viability results after 7 days of culture yielded significantly higher (p < 0.05) results in ß-TCP scaffolds compared to BG 45S5 and MBG groups. CONCLUSION: All materials expressed osteogenic markers after 21 days of culture in expansion and osteogenic media.

Derivaciones, procedimientos y complicaciones en servicios de cirugía bucal. Revisión de la literatura / Referrals, procedures and complications in oral surgery services. Literature review

Varios estudios han descrito y analizado el funcionamiento de los servicios quirúrgicos orales/bucales en miras a introducir mejoras de calidad y disponibilidad de la atención. El objetivo del presente artículo es revisar los patrones de derivación, procedimentales y de complicaciones descritos en la literatura de corriente principal. En estudios realizados principalmente en Inglaterra y África, se determinó que los procedimientos más frecuentes son de baja complejidad, principalmente exodoncias, y dentro de las exodoncias, primariamente terceros molares. En la mayoría de los procedimientos se utilizó anestesia local y el motivo más común de derivación fue por extracciones múltiples, quirúrgicas o complicadas. La derivación fue dada principalmente por el odontólogo general, y en menor cantidad por odontólogo especialista, médico general y médico especialista. Son pocos los procedimientos que generan complicaciones postquirúrgicas, dentro de las cuales está alvéolo seco, infección, inflamación y dolor alrededor de las suturas y hemorragias.

Several studies have described and analyzed performance of oral surgical services with the aim of introducing improvement in care quality and availability. The aim of the present article was to review referral, procedure and complication patterns described in scientific literature. In studies mainly conducted in the United Kingdom and Africa, it was determined that most frequent procedures are of low complexity, mainly extractions, and within extractions, those of third molars. Local anesthesia was used in most procedures, the most common reasons for referral were multiple, surgical or complicated extractions. Referral was mainly executed by the general dentist, and in lesser amounts by the specialist dentist, general physician and specialist physician. Few procedures cause post-surgical complications. Among these we can count dry socket, infection, inflammation, pain around sutures and hemorrhage.