Craniofacial Birth Defects Research Articles

Accelerating Oral Wound Healing Using Bilayer Biomaterial Delivery of FTY720 Immunotherapy.

Orofacial clefts are the most common congenital craniofacial anomaly. Adverse healing following cleft palate repair can lead to oronasal fistula (ONF), a persistent connection between the oral and nasal cavities. Although human allograft tissues are currently the gold standard for ONF repair, these methods carry risks of infection and rejection, often requiring surgical revision. Immunoregenerative therapies present a novel alternative approach to harness the body's immune response and enhance the wound healing environment. An FDA-approved immunomodulatory drug, FTY720, is repurposed to reduce lymphocyte egress and induce immune cell fate switching toward pro-regenerative phenotypes. In this study, a bilayer biomaterial system is engineered using Tegaderm to secure and control the delivery of FTY720-nanofiber scaffolds (FTY720-NF). The release kinetics of the bilayer FTY720-NF is optimized to maintain drug release for up to 7 days, ensuring safe transdermal absorption and tissue biodistribution. The comprehensive immunophenotyping results demonstrate a regenerative state transition in hybrid immune cells recruited to the wound site. Further, histological evaluations reveal a significant ONF closure in mice by day 7 following bilayer FTY720-NF implantation. These findings demonstrate the utility of immunomodulatory strategies for oral wound healing, better positing the field to develop more efficacious treatment options in pediatric patients.

Timely Access for Orofacial Cleft Repairs in a Brazilian Amazon Center.

Orofacial clefts are the most common congenital craniofacial anomalies worldwide, and if not managed in a timely manner, can lead to significant complications. We aim to examine surgical timing at one of the few cleft care centers in the North region of Brazil since its foundation in 2016. This retrospective, descriptive study analyzed medical records from 2016 to 2023. We calculated the age at surgery for each time period and each primary surgery performed. We also evaluated the number of procedures performed outside the recommended age. Of the 1439 procedures performed from 2016 to 2023, 713 procedures met our inclusion criteria. Among these, 66.67% (n=188) of primary cheiloplasties, 67.80% (n=40) of primary lip adhesions, and 54.57% (n=203) of palatoplasties were performed outside the recommended time frame. Of the surgeries performed, 45.16% (n=322) were between 2016 and 2019, while 54.84% (n=391) were from 2020 to 2023. Considering procedures performed within the ideal recommended age groups, only 32.92% (n=106) were done between 2016 and 2019, in contrast to 45.01% (n=176) between 2020 and 2023. In conclusion, since the inception of the specialized center, there has been an increase in surgical volume and an improvement in their timing. However, many surgeries are still being conducted outside the recommended time frame.

The prevalence of orofacial clefts in Qatar : a cross-sectional nationwide study

BackgroundCleft lip and palate are congenital craniofacial anomalies that significantly impact individuals and their families, both medically and psychosocially. The Qatari population has unique characteristics that are suggestive of a high prevalence of congenital anomalies: high consanguinity rate, large family size, advanced paternal age and high prevalence of certain genetic disorders. The lack of existing data concerning the epidemiology of cleft lip and/or palate in Qatar warrants a descriptive study addressing this topic.MethodsA retrospective nationwide hospital-based cross-sectional study conducted to determine the prevalence of orofacial clefts in Qatar from 2016 to 2021. Data were extracted from the corporation’s Cerner database and electronic health records. Information concerning the cleft’s characteristics, type, affected side, patient’s gender, presence of associated syndromes, nationality, and maternal age were collected.ResultsOut of the 147,727 live births, 148 had an orofacial cleft. The prevalence of cleft lip and/or palate was determined to be 1 per 1000 livebirths (95% CI: 0.85, 1.18). The prevalence of cleft lip was 0.18 (95% CI: 0.12, 0.27), cleft palate 0.39 (95% CI: 0.30, 0.51), and cleft lip and palate 0.43 (95% CI: 0.33, 0.55). Qataris had a prevalence of CL 0.25, CP 0.40, and CLP 0.56, compared to 0.16, 0.39, 0.39 for non-Qataris (p-value 0.186). Unilateral clefts predominated over bilateral (74.4% and 25.6%, respectively). Among the unilateral cases, 70.2% occurred on the left side. Most cases were isolated clefts, with only 10.2% having associated syndromes.ConclusionsThe prevalence of orofacial clefts in Qatar is consistent with the globally reported prevalence. Most cases were unilateral and on the left side. Associated syndromes were infrequent and more common with cleft palate alone. Intriguing patterns were revealed between Qatari nationals and non-Qatari residents, with specific subtypes of orofacial clefts showing higher prevalence among nationals.

Hemifacial microsomia – a review of the literature of current hypotheses of pathogenesis, and possible therapeutic methods

<b>Introduction:</b> Hemifacial microsomia (HFM) is the second most common congenital craniofacial anomaly.<b>Aim:</b> The aim of this study is to review data related to HFM.<b>Materials and methods:</b> Materials for the review were selected based on an analysis of publications published in the last 10 years.<b>Results:</b> There are three possible models of pathogenesis – vascular abnormalities, Meckel’s cartilage damage, and abnormal development of cranial neural crest cells – caused by genetic, maternal, and external factors. Symptoms results from disorders of structures originating from the first, and second branchial arches, most commonly resulting in mandibular hypoplasia, microtia or anotia, hypoplasia of the auditory ossicles, facial nerve paralysis, and soft tissue deficiency. The severity of the disorder varies greatly, depending on the number of structures involved, and the degree of penetration. The most common classification system (Orbit, Mandible, Ear, Nerve, Soft tissue; OMENS) has recently been proposed to assess the temporomandibular joint disc, and to assess disturbances originating from another structures. Other classifications such as FACIAL or ICHOM criteria have also been developed. The approach to treating each case should be individualized, primarily focusing on reconstructing the underdeveloped mandible, orthodontic treatment, creating the external ear, and filling soft tissue deficiencies.<b>Discussion:</b> The complexity of the condition is noted, as well as the need for interdisciplinary patient care.<b>Conclusions:</b> Through analysis of existing research, and clinical data, significant information regarding etiology, symptoms, possible classification systems, and therapeutic options has been gathered.

Pattern of Cleft Lip and Palate Clefts at a Tertiary Care Hospital in Saudi Arabia.

Clefts of the lip and palate (CL/P) and cleft palate (CP) are the most common craniofacial congenital anomalies. Clefts are classified as syndromic and nonsyndromic. Nonsyndromic clefts have no known genetic causes. This study combines prospective and retrospective studies to review the patterns of CL/P and CP and associated syndromes and conditions in patients registered for CL/P surgery at a tertiary care pediatric center in our tertiary care hospital in Saudi Arabia. It included patient data from May 2015 through April 2023. Patient record forms and SPSS (IBM version 20.0) were used to collect and analyze data. A significance level of 5% was used, with p ≤ 0.05 considered statistically significant. Of the 319 patients who met our inclusion criteria, 175 were male. Of the total, 99 had a left unilateral isolated cleft lip, 61 had a right unilateral isolated cleft lip, 69 had a bilateral cleft lip, and 90 had an isolated CP. Of the total, 140 had CL/P. Around 242 were nonsyndromic. The Chi-square test revealed a significant association between the prevalence of isolated CP and CLP and gender. The prevalence of left unilateral isolated cleft lip and bilateral and isolated CP was significantly associated with syndromic and nonsyndromic cases. Males are more likely to be affected by orofacial clefts, which is consistent with the global trend. Isolated CP was the most common orofacial cleft. Within the sample, syndromes' association with orofacial clefts was significantly weaker than that of isolated and bilateral clefts.

Mll4 regulates postnatal palate growth and midpalatal suture development.

MLL4, also known as KMT2D, is a histone methyltransferase that acts as an important epigenetic regulator during various organogenesis programs. Mutations in the MLL4 gene are the major cause for Kabuki syndrome, a human developmental disorder that involves craniofacial birth defects, including anomalies in the palate. The purpose of this study was to investigate the role of Mll4 and the underlying mechanisms in the development and growth of the palate. We generated a novel conditional knockout (cKO) mouse model with tissue-specific deletion of Mll4 in the palatal mesenchyme. By using micro-computed tomography (CT), histology, cell mechanism assays, and gene expression analysis approaches, we examined the development and growth of the palate in the Mll4 -cKO mice. Gross intra-oral examination at adult stages showed that Mll4 -cKO mice had defects along the midline of the palate, which included disrupted rugae pattern and widened midpalatal suture. Micro-CT-based skeletal analysis in the adult mice revealed that the overall palate width was decreased in the Mll4 -cKO mice. By using whole-mount and histological staining approaches at perinatal stages, we identified that the midline defects started to appear as early as 1 day prior to birth, manifesting initially as a widened midpalatal suture, accompanied by increased cell apoptosis in the suture mesenchyme cells. Genome-wide analysis of mRNA expression in the midpalatal suture tissue showed that Mll4 is essential for timely expression of major genes for cartilage development, such as Col2a1 and Acan , at birth. These results were validated through immunofluorescence staining, confirming that the expression of chondrogenic markers Sox9 and Col2a1 were markedly decreased, whereas that of the osteogenic marker Runx2 remained unchanged, in the midpalatal suture of the Mll4 -cKO mice. Indeed, time-course histological analysis during postnatal palate growth revealed retardation in the development of the suture cartilage in the Mll4 -cKO mice. In parallel, time-course micro-CT analysis during postnatal palatogenesis confirmed a transverse growth deficit in the palate of the Mll4 -cKO mice. Taken together, our results show that Mll4 is essential for timely occurrence of key cellular and molecular events that lead to proper midpalatal suture development and palate growth.

Does a Point-of-Care 3-Dimensional Printer Result in a Decreased Length of Surgery for Orbital Fractures?

Utilization of point-of-care 3-dimensional printing (3DP) has decreased length of surgery in facial trauma. Little is known regarding 3DP's impact on length of surgery in orbital fracture. The purpose of this study was to compare length of surgery between 3DP/preadapted (3DPPA) orbital plates and intraoperative adapted plates (IOAP) for orbital fracture reconstruction. This was a prospective, non-blinded, randomized clinical study of consecutive subjects with orbital fractures presented to Grady Memorial Hospital in Atlanta, Georgia, between January 2018 and June 2021. Subjects ≥ 18years, unilateral fracture, no previous orbital surgery, and/or congenital craniofacial anomaly were included. We excluded subjects <18years and bilateral fractures. Primary predictor variable was the treatment approach. Randomization software was used, and subjects were randomized to 3DPPA or IOAP groups. Primary outcome variable was length of surgery in minutes. Secondary outcomes were the time required for plate insertion and fixation in minutes, operating room (OR) charges, and orbital volume (OV) calculation. Age, sex, race, etiology, laterality, location, dimension, indication for surgery, postoperative enophthalmos, and diplopia. Univariate and bivariate analyses were calculated. Statistical significance was P<.05. Twenty-five subjects met the inclusion criteria. Mean ages in 3DPPA and conventional IOAP groups were 41.5 (±9) and 38.2 (±10, P=.31), respectively. The mean length of surgery was 32.6 (±13.7) in 3DPPA and 53.3 (±12.8, P<.001) in conventional IOAP. The mean time required for plate insertion and fixation was 15.8n (±14.4) in 3DPPA and 41.4 (±9.4, P<.001) in conventional IOAP. The mean OR charges were $1,072.5 (±524.6) in 3DPPA and $1,757.3 (±422.6, P ≤ 0.001) in conventional IOAP. The mean calculated OV of uninjured and reconstructed orbit for the 3DPPA was 23.5 (±3.2)cm3 and 23 (±3.5, P=.37)cm3, respectively. The mean calculated OV of uninjured and reconstructed orbit for conventional IOAP was 28.6 (±3.6)cm3 and 22.8 (±2.6, P<.001)cm3, respectively. Using 3DP to produce a model that enables preoperative plate bending/adaptation reduces the length of surgery, decreases OR charges, and results in predictable OV.

Cleft Lip Surgery in Sudan: Clinical Presentations, Early Outcomes, and Patient and Professional Satisfaction: A sub-Saharan African experience

BackgroundCleft lip and palate are the most common congenital craniofacial anomalies. They account for approximately 13% of all congenital anomalies. ObjectivesTo study the presentation of cleft lip and the early results of surgical repair among patients who presented to our centers. MethodsThis was a hospital-based prospective cohort study of 72 patients who underwent cleft lip repair in Sudan. ResultsThe commonest age group was between 10–18 months. The male-to-female ratio was 2:1, and a family history of cleft lip was found in 2.8% of patients. The cleft lip was complete in 81.9%, incomplete in 12.5%, and hybrid in 5.6% of patients. Associated cleft palate was observed in 54 patients. Associated syndromes were found in 10 patients. The surgery was carried out in most patients at 9 months or less; in 4 patients, it was more than 18 months. Achievement of reasonable lip repair was moderate (50% collectively). High achievement was observed for criteria, such as accurate union (90.3%), and sub-moderate achievement in even vermillion border and cupid's bow (44%), low nose symmetry (30.6%), and quality of scar (18.1%). Early complications were reported at the rate of 13.9%. Patient satisfaction was 59.7%; however, the professionals showed higher satisfaction levels (66.7%). The anthropometric measurements of normal infants were moderately similar to those of the infants who underwent surgery. ConclusionThe patients with cleft lip showed early presentation, with a predominance of the male gender and left side pattern. The preliminary outcome of cleft lip repair was moderate, with variations in different criteria. Patient and professional satisfaction were above average.

The Accuracy of Digital Impressions versus Conventional Impressions in Neonates with Cleft Lip and/or Palate: A Laboratory-Based Study.

Cleft lip and palate (CL/P) are a common congenital craniofacial anomaly requiring precise impressions for effective treatment. Conventional impressions (CIs) pose challenges in neonates with CL/P due to their delicate oral anatomy. While digital impressions (DIs) are increasingly recognised for their potential benefits over conventional methods in dentistry, their accuracy and application in neonates with cleft lip and palate (CL/P) remain underexplored. This study aimed to assess the accuracy of DIs compared to CIs in neonates with CL/P, using alginate and putty materials as references. A laboratory-based case-control study was conducted, utilising soft acrylic models resembling neonatal mouths with CL/P. Alginate and putty impressions were obtained conventionally, while digital impressions were captured using an intraoral scanner (IOS). A total of 42 models were analysed, divided evenly into three groups, with each group comprising 14 models. Superimposition and surface discrepancy analyses were performed to evaluate impression accuracy. The results revealed no statistically significant differences between the digital and conventional impressions in their intra-arch measurements and surface discrepancies. The mean measurement values did not significantly differ among groups, with p values indicating no significant variations (p > 0.05), confirmed by an analysis of variance. High intra-examiner reliability with Intra Class Coefficient (ICC) values close to 1 indicated consistent measurements over time. The current study demonstrates that DIs are equally accurate as conventional alginate and putty impressions in neonates with cleft lip and palate, offering a viable and less invasive alternative for clinical practise. This advancement holds promise for improving the treatment planning process and enhancing patient comfort, particularly in vulnerable neonatal populations. Further research is warranted to explore the clinical implications and factors affecting DI accuracy in this population.

A single-center prospective study of perioperative anesthetic complications in cleft lip, alveolus, and palate surgeries in a teaching hospital in Lagos, Nigeria

ABSTRACT Background: Cleft lip and/or palate are one of the most common congenital craniofacial anomalies that require surgical management. Patients undergoing primary cleft repair are at increased risk of perioperative anesthetic complications due to their young age and anatomical defects. Aim: This study aimed to present the frequency of perioperative airway-related morbidities in the anesthetic management of cleft lip, alveolus, and palate surgeries. Patients and Methods: This study was conducted at Lagos University Teaching Hospital, Nigeria. Patients undergoing cleft lip, alveolus, or palate repair were prospectively studied from January 2015 to December 2019. Data on patient demography, type of cleft, presence of syndromes and other deformities, and intra- and postoperative complications were collected. Results: A total of 150 patients were included, with a median age of 15.5 months, and 67 (44.7%) of the patients were &lt;12 months old. Most patients were female (56%), and the most common type of cleft was lip, alveolus, and palate (36.6%). Sixteen (10.7%) of the patients had associated syndromes. Notably, intraoperative complications were observed in 5 (3.3%) patients, including laryngospasm and difficult intubation. Postoperative complications were rare, with one case of nasal bleeding. Significant associations between presence of other deformities and syndromes and intraoperative complications were noted (P &lt; 0.05). Conclusion: Patients with orofacial clefts and other deformities tend to be predisposed to anesthetic complications. However, the incidence of anesthetic complications in this study was low (3.3%) probably because the current protocol used in the author’s hospital for cleft surgeries was followed and appropriate.

Retinoic Acid Upregulates METTL14 Expression and the m6A Modification Level to Inhibit the Proliferation of Embryonic Palate Mesenchymal Cells in Cleft Palate Mice.

Cleft palate only (CPO) is one of the most common craniofacial birth defects. Environmental factors can induce cleft palate by affecting epigenetic modifications such as DNA methylation, histone acetylation, and non-coding RNA. However, there are few reports focusing on the RNA modifications. In this study, all-trans retinoic acid (atRA) was used to simulate environmental factors to induce a C57BL/6J fetal mouse cleft palate model. Techniques such as dot blotting and immunofluorescence were used to find the changes in m6A modification when cleft palate occurs. RNA-seq and KEGG analysis were used to screen for significantly differentially expressed pathways downstream. Primary mouse embryonic palate mesenchymal (MEPM) cells were successfully isolated and used for in vitro experimental verification. We found that an increased m6A methylation level was correlated with suppressed cell proliferation in the palatine process mesenchyme of cleft palate mice. This change is due to the abnormally high expression of m6A methyltransferase METTL14. When using siRNAs and the m6A methyltransferase complex inhibitor SAH to interfere with the expression or function of METTL14, the teratogenic effect of atRA on primary cells was partially alleviated. In conclusion, METTL14 regulates palatal mesenchymal cell proliferation and cycle-related protein expression relies on m6A methylation modification, affecting the occurrence of cleft palate.

Dyrk1a is required for craniofacial development in Xenopus laevis.

Loss of function variations in the dual specificity tyrosine-phosphorylation-regulated kinase 1 A (DYRK1A) gene are associated with craniofacial malformations in humans. Here we characterized the effects of deficient DYRK1A in craniofacial development using a developmental model, Xenopus laevis. Dyrk1a mRNA and protein were expressed throughout the developing head and both were enriched in the branchial arches which contribute to the face and jaw. Consistently, reduced Dyrk1a function, using dyrk1a morpholinos and pharmacological inhibitors, resulted in orofacial malformations including hypotelorism, altered mouth shape, slanted eyes, and narrower face accompanied by smaller jaw cartilage and muscle. Inhibition of Dyrk1a function resulted in misexpression of key craniofacial regulators including transcription factors and members of the retinoic acid signaling pathway. Two such regulators, sox9 and pax3 are required for neural crest development and their decreased expression corresponds with smaller neural crest domains within the branchial arches. Finally, we determined that the smaller size of the faces, jaw elements and neural crest domains in embryos deficient in Dyrk1a could be explained by increased cell death and decreased proliferation. This study is the first to provide insight into why craniofacial birth defects might arise in humans with variants of DYRK1A.

A BMP-controlled metabolic/epigenetic signaling cascade directs midfacial morphogenesis.

Craniofacial anomalies, especially midline facial defects, are among the most common birth defects in patients and are associated with increased mortality or require lifelong treatment. During mammalian embryogenesis, specific instructions arising at genetic, signaling, and metabolic levels are important for stem cell behaviors and fate determination, but how these functionally relevant mechanisms are coordinated to regulate craniofacial morphogenesis remain unknown. Here, we report that bone morphogenetic protein (BMP) signaling in cranial neural crest cells (CNCCs) is critical for glycolytic lactate production and subsequent epigenetic histone lactylation, thereby dictating craniofacial morphogenesis. Elevated BMP signaling in CNCCs through constitutively activated ACVR1 (ca-ACVR1) suppressed glycolytic activity and blocked lactate production via a p53-dependent process that resulted in severe midline facial defects. By modulating epigenetic remodeling, BMP signaling-dependent lactate generation drove histone lactylation levels to alter essential genes of Pdgfra, thus regulating CNCC behavior in vitro as well as in vivo. These findings define an axis wherein BMP signaling controls a metabolic/epigenetic cascade to direct craniofacial morphogenesis, thus providing a conceptual framework for understanding the interaction between genetic and metabolic cues operative during embryonic development. These findings indicate potential preventive strategies of congenital craniofacial birth defects via modulating metabolic-driven histone lactylation.

Dynamic enhancer landscapes in human craniofacial development

The genetic basis of human facial variation and craniofacial birth defects remains poorly understood. Distant-acting transcriptional enhancers control the fine-tuned spatiotemporal expression of genes during critical stages of craniofacial development. However, a lack of accurate maps of the genomic locations and cell type-resolved activities of craniofacial enhancers prevents their systematic exploration in human genetics studies. Here, we combine histone modification, chromatin accessibility, and gene expression profiling of human craniofacial development with single-cell analyses of the developing mouse face to define the regulatory landscape of facial development at tissue- and single cell-resolution. We provide temporal activity profiles for 14,000 human developmental craniofacial enhancers. We find that 56% of human craniofacial enhancers share chromatin accessibility in the mouse and we provide cell population- and embryonic stage-resolved predictions of their in vivo activity. Taken together, our data provide an expansive resource for genetic and developmental studies of human craniofacial development.

A comprehensive consolidation of data on the relationship between IRF6 polymorphisms and non-syndromic cleft lip/palate susceptibility: From 79 case-control studies

BackgroundNon-syndromic cleft lip with or without cleft palate (NSCL/P) is a prevalent craniofacial birth defect on a global scale. A number of candidate genes have been identified as having an impact on NSCL/P. However, the association between interferon regulatory factor 6 (IRF6) polymorphisms and NSCL/P has yielded inconsistent results, prompting the need for a meta-analysis to obtain more accurate estimates. MethodsWe conducted a thorough screening of all relevant articles published up until November 15, 2023, in online bibliographic databases. The statistical analysis of the collected data was performed using the Comprehensive Meta-Analysis (Version 4.0) software. ResultsA total of 79 case-control studies, comprising 14,003 cases and 19,905 controls, were included in our analysis. The combined data indicated that the IRF6 rs642961 and rs2235371 polymorphisms were associated with an increased risk of NSCL/P in the overall population. However, no significant association was found between the rs2013162 and rs2235375 polymorphisms and the risk of NSCL/P in the overall population. Furthermore, subgroup analyses revealed significant correlations between the IRF6 rs642961, rs2235371, and rs2235375 polymorphisms and the risk of NSCL/P based on ethnic background and country of origin. Nevertheless, the rs2013162 polymorphism plays a protective role in Caucasians and mixed populations. ConclusionsOur collective data indicates a significant association between the rs642961 and rs2235371 polymorphisms and the risk of NSCL/P in the overall population. The rs2235375 polymorphism could influence the susceptibility to NSCL/P based on ethnic background. Meanwhile, the rs2013162 polymorphism provides protective effects in Caucasian, mixed populations, and the Brazilian population.

Prenatal incidence of cleft lip/palate and cocaine abuse in parents: a systematic review and meta-analysis.

The study aimed to investigate the association between maternal cocaine abuse during pregnancy and the prevalence of cleft lip/palate (CL/P) in offspring, synthesizing existing evidence through a systematic review and meta-analysis. CL/P is a congenital craniofacial anomaly with complex etiology, and prior research has suggested potential links between maternal cocaine use and CL/P. However, these associations remain inconclusive. A comprehensive literature search was conducted to identify relevant studies published up to the study's cutoff date in September 2021. Several databases were systematically searched using predefined search terms. Inclusion criteria were set to encompass studies reporting on the prevalence of CL/P in infants born to mothers with a history of cocaine use during pregnancy, with a comparison group of non-cocaine-using mothers. Data were extracted, and a meta-analysis was performed using a random-effects model to calculate pooled odds ratios (OR) and relative risks (RR) with their respective 95% confidence intervals (CI). The review included data from 4 studies that met the inclusion criteria. The combined OR from two studies was 0.05 (95% CI: 0.00, 4.41), which does not suggest a statistically significant association between prenatal cocaine exposure and the incidence of CL/P due to the confidence interval crossing the null value. Additionally, the combined RR was 0.17 (95% CI: 0.04, 0.66), indicating a statistically significant decrease in the risk of CL/P associated with prenatal cocaine exposure. These results, with an OR that is not statistically significant and an RR suggesting decreased risk, should be interpreted with caution due to considerable heterogeneity and variability among the included studies' findings. Further research is needed to clarify these associations. The findings from this systematic review and meta-analysis suggest that maternal cocaine use during pregnancy is not a statistically significant independent risk factor for the development of CL/P in offspring. These results underscore the multifactorial nature of CL/P etiology and emphasize the importance of considering other genetic, environmental, and nutritional factors in understanding the condition's origins. While the study provides important insights, limitations such as data heterogeneity and potential confounders should be acknowledged. Future research should adopt rigorous study designs and explore a broader range of potential risk factors to comprehensively elucidate CL/P development.

Holoprosencefalia associada a sinoftalmia e arinia em felino (Felis catus): relato de caso

The aim of this study was to describe the macroscopic and histological lesions observed in domestic newborn felines with facial lesions characterized by holoprosencephaly associated with synophthalmia and arhinia. A feline with multiple craniofacial congenital anomalies was necropsied, and the brain was collected, followed by photodocumentation and histopathological processing with H&amp;E. The diagnosis of alobar holoprosencephaly with grade (I) morphological lesions of the face was made through the anatomopathological changes observed during the clinical and necroscopic examination, characterized by deformation of the cerebral hemispheres, shown failure in the forebrain vesicle development, located in the cranial neural tube part, associated with craniofacial dysmorphisms. In the microscopic study of the CNS, lesions characterized by abnormal lamination of the cerebral hemisphere's outermost cell layers and multiple areas of vacuolization of the cortex and in the cerebellum low cell density of the granular layer, with the presence of large intracytoplasmic vacuoles and absence of Purkinje cells were observed. It was not possible to determine the deformation cause, since laboratory tests were not performed, as well as the association with the FeLV virus.

The presence and distribution of various genes in postnatal CLP-affected palatine tissue

BackgroundWorldwide cleft lip with or without a cleft palate (CL/P) is the most common craniofacial birth defect. Apart from changes in facial appearance, additionally affected individuals often suffer from various associated comorbidities requiring complex multidisciplinary treatment with overall high expenses. Understanding the complete pathogenetic mechanisms of CL/P might aid in developing new preventative strategies and therapeutic approaches, help with genetic counselling, and improve quality of life. Many genes have been associated with the development of orofacial clefts; however, the majority require further research. Based on the role of PAX7, PAX9, SHH, SOX3, WNT3A, and WNT9B in orofacial development, the intention was to use chromogenic in situ hybridization to detect the six genes in postnatal CLP-affected palatine tissue and compare their distribution within the tissue samples.ResultsStatistically significant differences in the distribution of PAX7, PAX9, WNT3A, and WNT9B were observed. In total, 19 pairs of moderate to very strong positive correlations were noted.ConclusionsChanges in the cleft-affected palatine epithelium primarily seem to be associated with the PAX7 gene; however, PAX9, WNT3A, WNT9B, and SOX3 role seems to be more limited. Whilst connective tissue changes seem to depend on PAX7 only, SHH seems to participate individually and indistinctly. Numerous positive correlations reflect the complicating interactions of the pathways and their components in the orofacial cleft morphopathogenesis.

Prevalence, trend, and associated risk factors for cleft lip with/without cleft palate: a national study on live births from 2016 to 2021

BackgroundsCleft lip with or without cleft palate (CL/P) is the most common congenital craniofacial anomaly, including non-syndromic cleft lip with or without cleft palate and cleft palate only. Failure in the fusion of median and lateral nasal processes, the maxillary prominence, and soft tissues around the oral cavity can cause CL/P. Previously, the prevalence has been estimated to be 1 among every 1000 births in 2014 among American neonates and no other reports have been available since. Thus, this study aimed to calculate the prevalence and trend of isolated CL/P among American live births from 2016 to 2021 with its associated risk factors.Methods and materialsIn this cross-sectional population-based retrospective study, we used live birth data provided by the National Center for Health Statistics (NCHS) from the Center for Disease Control and Prevention (CDC). We calculated the prevalence per 10,000 live births of isolated (non-syndromic) CL/P from 2016 to 2021. To examine risk factors for developing isolated CL/P, we used logistic regression modelling.ResultsThe total prevalence per 10,000 births from 2016 to 2021 was 4.88 (4.79–4.97), for both sexes, and 5.96 (5.82–6.10) for males, and 3.75 (3.64–3.87) for females. The prevalence did not show any consistent linear decreasing or increasing pattern. We found significant association between increased odds of developing isolated CL/P among cases with 20 to 24 year-old mothers (OR = 1.07, 1.01–1.13, p = 0.013), mothers who smoked 11 to 20 cigarettes per day (OR = 1.46, 1.33–1.60, p < 0.001), mothers with extreme obesity (OR = 1.32, 1.21–1.43, p < 0.001), mothers with grade II obesity (OR = 1.32, 1.23–1.42, p < 0.001), mothers with pre-pregnancy hypertension (OR = 1.17, 1.04–1.31, p = 0.009), mothers with pre-pregnancy diabetes mellitus (OR = 1.96, 1.71–2.25, p < 0.001), and mothers who used assisted reproductive technology (OR = 1.40, 1.18–1.66, p < 0.001).ConclusionsOur findings suggest a minuscule increase, albeit insignificant, in the trend of CL/P prevalence from 2016 to 2021. Developing CL/P had greater odds among mothers with pre-pregnancy diabetes, smoking, obesity, and pre-pregnancy hypertension mothers along with mothers who used assisted reproductive technology. Isolated CL/P had the highest prevalence in non-Hispanic Whites, American Indian or Alaskan Native and Native Hawaiian and Other Pacific Islanders.

Physicochemical and biocompatibility characterisation of a 3D lyophilised platelet-rich fibrin scaffold for cleft lip and palate repair.

Craniofacial bone defects result from various disorders such as trauma, congenital malformations and infections. Cleft lip and palate are the most prevalent congenital craniofacial birth defect in humans. Growth factors (GFs) are soluble proteins secreted by cells that regulate various cellular processes and tissue regeneration. At present, developing three-dimensional scaffolds for delivering GFs to the site of injury has become an important aspect in craniofacial bone regeneration. This study aims to develop a novel 3D bone substitute using lyophilized-platelet-rich fibrin (LyPRF) biocomposite scaffolds for potential application for CLP repair. Collagen (C), bioglass (BG), and LyPRF were used to fabricate a biocomposite (C-BG-LyPRF) scaffold. The physical, chemical, and biocompatibility properties of the scaffold were evaluated. The C-BG-LyPRF scaffold demonstrated a mean pore diameter of 146 µm within a porosity of 87.26%. The FTIR spectra verified the presence of am-ide I, II, and III functional groups. The inorganic phase of the C-BG-LyPRF scaffold was composed of sodium, calcium, silicon, and phosphorus, as determined by EDX analysis. Furthermore, C-BG-LyPRF scaffold was biocompatible with MC3T3-E1 cells in both the Live/Dead and prolif-eration assays. Data demonstrate the developed C-BG-LyPRF scaffold exhibits biomimetic and biocompatibility properties, establishing it as a promising biomaterial for craniofacial regeneration.