ResearchPad - palate https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[The emerging risk of oropharyngeal and oral cavity cancer in HPV-related subsites in young people in Brazil]]> https://www.researchpad.co/article/elastic_article_14563 Human papillomavirus (HPV) is responsible for the rise in the incidence of cancer in the oropharynx, tonsils, and base of the tongue (i.e., HPV-related subsites). HPV triggered the changes in the epidemiology of oropharyngeal and oral cavity cancer (OPC/OCC) in Asia, Europe, North America, and Oceania. Hence, the incidence of cancer in HPV-related subsites is augmenting, while that in other HPV-unrelated subsites is decreasing. In South America, although the incidence of HPV-positive tumors has gradually increased, there is an atypically low prevalence of HPV in people with OPC/OCC. To clarify whether this dramatic shift in incidence trends also occurred in this population, we estimated the burden of HPV on the incidence trends of OPCs/OCCs in São Paulo city in Brazil. In this population-based study, we categorized OPCs/OCCs by HPV-related and HPV-unrelated subsites. We used Poisson regression to assess the age-standardized incidence rates (ASRs) stratified by sex and age groups, as well as to examine the age-period-cohort effects. There were 15,391 cases of OPCs/OCCs diagnosed in HPV-related (n = 5,898; 38.3%) and HPV-unrelated (n = 9,493; 61.7%) subsites. Overall, the ASRs decreased for most subsites, for both sexes and for all age groups, except for HPV-related OPC/OCC in young males and females, which increased by 3.8% and 8.6% per year, respectively. In the birth-cohort-effect analysis, we identified an increasing risk for HPV-related OPC/OCC in both sexes in recent birth cohorts; however, this risk was sharply decreased in HPV-unrelated subsites. Our data demonstrate an emerging risk for HPV-related OPC/OCC in young people, which supports prophylactic HPV vaccination in this group.

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<![CDATA[Flat Feline Faces: Is Brachycephaly Associated with Respiratory Abnormalities in the Domestic Cat (Felis catus)?]]> https://www.researchpad.co/article/5989daf3ab0ee8fa60bc1ffa

There has been little research into brachycephalism and associated disorders in cats. A questionnaire aimed at cat owners was used to determine the relationship between feline facial conformation and owner-reported cat management requirements and respiratory abnormalities. Owner-submitted photographs of cats were used to develop novel measures of skull conformation. One thousand valid questionnaires were received. Within these there were 373 valid photographs that allowed measurement of muzzle ratio (M%) and 494 that allowed nose position ratio (NP%). The data included 239 cats for which both measurements were available. Owners reported lifestyle factors (e.g. feeding type, grooming routine, activity level), physical characteristics (e.g. hair length) and other health characteristics of their cat (e.g. tear staining, body condition score). A composite respiratory score (RS) was calculated for each cat using their owner’s assessment of respiratory noise whilst their cat was asleep and then breathing difficulty following activity. Multivariate analyses were carried out using linear models to explore the relationship between RS and facial conformation, and lifestyle risk factors. The results showed that reductions in NP% and M% were significantly associated with RS (P < 0.001 and P = 0.026, respectively) and that the relationship was significantly negatively correlated (r = -0.56, P < 0.001 for both). Respiratory score was also significantly associated with increased presence of tear staining (P < 0.001) and a sedentary lifestyle (P = 0.01). This study improves current knowledge concerning cats with breeding-related alterations in skull confirmation and indicates that brachycephalism may have negative respiratory implications for cat health and welfare, as has been previously shown in dogs.

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<![CDATA[Meta-analysis Reveals Genome-Wide Significance at 15q13 for Nonsyndromic Clefting of Both the Lip and the Palate, and Functional Analyses Implicate GREM1 As a Plausible Causative Gene]]> https://www.researchpad.co/article/5989da70ab0ee8fa60b94768

Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO, respectively). Although genetic components play an important role in nsCLP, the genetic factors that predispose to palate involvement are largely unknown. In this study, we carried out a meta-analysis on genetic and clinical data from three large cohorts and identified strong association between a region on chromosome 15q13 and nsCLP (P = 8.13×10−14 for rs1258763; relative risk (RR): 1.46, 95% confidence interval (CI): 1.32–1.61)) but not nsCLO (P = 0.27; RR: 1.09 (0.94–1.27)). The 5 kb region of strongest association maps downstream of Gremlin-1 (GREM1), which encodes a secreted antagonist of the BMP4 pathway. We show during mouse embryogenesis, Grem1 is expressed in the developing lip and soft palate but not in the hard palate. This is consistent with genotype-phenotype correlations between rs1258763 and a specific nsCLP subphenotype, since a more than two-fold increase in risk was observed in patients displaying clefts of both the lip and soft palate but who had an intact hard palate (RR: 3.76, CI: 1.47–9.61, Pdiff<0.05). While we did not find lip or palate defects in Grem1-deficient mice, wild type embryonic palatal shelves developed divergent shapes when cultured in the presence of ectopic Grem1 protein (P = 0.0014). The present study identified a non-coding region at 15q13 as the second, genome-wide significant locus specific for nsCLP, after 13q31. Moreover, our data suggest that the closely located GREM1 gene contributes to a rare clinical nsCLP entity. This entity specifically involves abnormalities of the lip and soft palate, which develop at different time-points and in separate anatomical regions.

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<![CDATA[Cone-beam computed tomography evaluation of the maxillofacial features of patients with unilateral temporomandibular joint ankylosis undergoing condylar reconstruction with an autogenous coronoid process graft]]> https://www.researchpad.co/article/5989db4fab0ee8fa60bdbce1

Objective

To evaluate the changes in the jaws and the upper airways of unilateral temporomandibular joint ankylosis patients who underwent condylar reconstruction via autogenous coronoid process grafts using cone-beam computed tomography (CBCT).

Study design

The 27 included patients underwent CBCT examinations at three stages: T0 (within two weeks before surgery), T1 (two weeks after surgery), and T2 (an average of 13 months after surgery). Forty items related to the maxillofacial hard tissues and the upper airway collected at the three times and the coronoid process graft volumes after surgery were compared.

Results

Some integral items related to the mandibular hard tissues exhibited statistical difference shortly after surgery. Some integral items related to maxillofacial hard tissues changing obviously long period after surgery may result from graft remodeling. Asymmetry-related item regarding local neo-condyle and some airway items were significantly different between T0 and T1. Due to variations in graft remodeling, some related local asymmetry items and airway items differed significantly between T0 and T2.

Conclusions

Anteriorly and inferiorly located neo-condyles and a trend toward the pronation of the mandible were observed and the narrowness of the upper airway was improved shortly after surgery. The grafts remodeled differently and some integral and asymmetry items related to neo-condyle changed. The improvements in the upper airway were slightly reduced.

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<![CDATA[Magnitude of Birth Defects in Central and Northwest Ethiopia from 2010-2014: A Descriptive Retrospective Study]]> https://www.researchpad.co/article/5989da12ab0ee8fa60b79e6e

Background

Birth defects are defined as structural and functional defects that develop during the organogenesis period and present at birth or detected later in life. They are one of the leading causes of infant and child mortality, morbidity, and long term disability. The magnitude of birth defects varies from country to country and from race/ethnicity to race/ethnicity, and about 40–60% of their causes are unknown. The known causes of birth defects are genetic and environmental factors which may be prevented. For various reasons, there is lack of data and research on birth defects in Ethiopia.

Objective

The major objective of this study is to estimate the magnitude of birth defects in Ethiopia.

Subject and Methods

A hospital based, retrospective, cross sectional, descriptive study was conducted. The subjects were babies/children aged 0–17years who visited selected hospitals between 2010 and 2014. Fourteen hospitals (8 in Addis Ababa, 6 in Amhara Region) were selected purposively based on case load. A data retrieving form was developed to extract relevant information from record books.

Results

In the hospitals mentioned, 319,776 various medical records of children aged 0–17years were found. Of these, 6,076 (1.9% with 95% CI: 1.85%–1.95%) children were diagnosed as having birth defects. The majority (58.5%) of the children were male and 41.5% female. A slightly more than half (51.1%) of the children were urban dwellers, while 48.9% were from rural areas. Among the participants of the study the proportion of birth defects ranged as follows: orofacial (34.2%), neural tube (30.8%), upper and lower limb (12.8%), cardiovascular system (10.3%), digestive system and abdominal wall (4.8%), unspecified congenital malformations (2.5%), Down syndrome (2%), genitourinary system (2%), head, face, and neck defects (0.4%), and others (0.3%). The trend of birth defects increased linearly over time [Extended Mantel-Haenszel chi square for linear trend = 356.7 (P<0.0001)]. About 275 (4.5%) of the cases had multiple (associated) birth defects and 5,801 (95.5%) isolated (single) birth defects. Out of the total birth defects, 6,018 (99%) were major and 58 (1%) minor.

Conclusion

The magnitude of birth defects increased from 2010–2014. Orofacial and neural tube defects contributed about two thirds of the birth defects. There is an urgent need for registry and surveillance system strategies for intervention and control of birth defects in Ethiopia.

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<![CDATA[Joint Testing of Genotypic and Gene-Environment Interaction Identified Novel Association for BMP4 with Non-Syndromic CL/P in an Asian Population Using Data from an International Cleft Consortium]]> https://www.researchpad.co/article/5989da65ab0ee8fa60b91cc4

Background

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common disorder with complex etiology. The Bone Morphogenetic Protein 4 gene (BMP4) has been considered a prime candidate gene with evidence accumulated from animal experimental studies, human linkage studies, as well as candidate gene association studies. The aim of the current study is to test for linkage and association between BMP4 and NSCL/P that could be missed in genome-wide association studies (GWAS) when genotypic (G) main effects alone were considered.

Methodology/Principal Findings

We performed the analysis considering G and interactions with multiple maternal environmental exposures using additive conditional logistic regression models in 895 Asian and 681 European complete NSCL/P trios. Single nucleotide polymorphisms (SNPs) that passed the quality control criteria among 122 genotyped and 25 imputed single nucleotide variants in and around the gene were used in analysis. Selected maternal environmental exposures during 3 months prior to and through the first trimester of pregnancy included any personal tobacco smoking, any environmental tobacco smoke in home, work place or any nearby places, any alcohol consumption and any use of multivitamin supplements. A novel significant association held for rs7156227 among Asian NSCL/P and non-syndromic cleft lip and palate (NSCLP) trios after Bonferroni correction which was not seen when G main effects alone were considered in either allelic or genotypic transmission disequilibrium tests. Odds ratios for carrying one copy of the minor allele without maternal exposure to any of the four environmental exposures were 0.58 (95%CI = 0.44, 0.75) and 0.54 (95%CI = 0.40, 0.73) for Asian NSCL/P and NSCLP trios, respectively. The Bonferroni P values corrected for the total number of 117 tested SNPs were 0.0051 (asymptotic P = 4.39*10−5) and 0.0065 (asymptotic P = 5.54*10−5), accordingly. In European trios, no significant association was seen for any SNPs after Bonferroni corrections for the total number of 120 tested SNPs.

Conclusions/Significance

Our findings add evidence from GWAS to support the role of BMP4 in susceptibility to NSCL/P originally identified in linkage and candidate gene association studies.

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<![CDATA[Accelerated Wound Closure In Vitro by Fibroblasts from a Subgroup of Cleft Lip/Palate Patients: Role of Transforming Growth Factor-α]]> https://www.researchpad.co/article/5989da75ab0ee8fa60b9644f

In a fraction of patients surgically treated for cleft lip/palate, excessive scarring disturbs maxillary growth and dento-alveolar development. Since certain genes are involved in craniofacial morphogenesis as well as tissue repair, a primary defect causing cleft lip/palate could lead to altered wound healing. We performed in vitro wound healing assays with primary lip fibroblasts from 16 cleft lip/palate patients. Nine foreskin fibroblast strains were included for comparison. Cells were grown to confluency and scratch wounds were applied; wound closure was monitored morphometrically over time. Wound closure rate showed highly significant differences between fibroblast strains. Statistically, fibroblast strains from the 25 individuals could be divided into three migratory groups, namely “fast”, “intermediate”, and “slow”. Most cleft lip/palate fibroblasts were distributed between the “fast” (5 strains) and the “intermediate” group (10 strains). These phenotypes were stable over different cell passages from the same individual. Expression of genes involved in cleft lip/palate and wound repair was determined by quantitative PCR. Transforming growth factor-α mRNA was significantly up-regulated in the “fast” group. 5 ng/ml transforming growth factor-α added to the culture medium increased the wound closure rate of cleft lip/palate strains from the “intermediate” migratory group to the level of the “fast”, but had no effect on the latter group. Conversely, antibody to transforming growth factor-α or a specific inhibitor of its receptor most effectively reduced the wound closure rate of “fast” cleft lip/palate strains. Thus, fibroblasts from a distinct subgroup of cleft lip/palate patients exhibit an increased migration rate into wounds in vitro, which is linked to higher transforming growth factor-α expression and attenuated by interfering with its signaling.

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<![CDATA[BMP4 Was Associated with NSCL/P in an Asian Population]]> https://www.researchpad.co/article/5989db0fab0ee8fa60bcb88a

Background

The Bone Morphogenetic Protein 4 gene (BMP4) is located in chromosome 14q22-q23 which has shown evidence of linkage for isolated nonsyndromic cleft lip with or without cleft palate (NSCL/P) in a genome wide linkage analysis of human multiplex families. BMP4 has been shown to play crucial roles in lip and palatal development in animal models. Several candidate gene association analyses also supported its potential risk for NSCL/P, however, results across these association studies have been inconsistent. The aim of the current study was to test for possible association between markers in and around the BMP4 gene and NSCL/P in Asian and Maryland trios.

Methodology/Principal Findings

Family Based Association Test was used to test for deviation from Mendelian assortment for 12 SNPs in and around BMP4. Nominal significant evidence of linkage and association was seen for three SNPs (rs10130587, rs2738265 and rs2761887) in 221 Asian trios and for one SNP (rs762642) in 76 Maryland trios. Statistical significance still held for rs10130587 after Bonferroni correction (corrected p = 0.019) among the Asian group. Estimated odds ratio for carrying the apparent high risk allele at this SNP was 1.61 (95%CI = 1.20, 2.18).

Conclusions

Our results provided further evidence of association between BMP4 and NSCL/P.

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<![CDATA[A Survey of Congenital Heart Disease and Other Organic Malformations Associated with Different Types of Orofacial Clefts in Eastern China]]> https://www.researchpad.co/article/5989da13ab0ee8fa60b7a67e

Background

A high incidence of orofacial clefts is reported in China, but no data has shown the relation between cleft types and the incidence of other defects so far. The aim of this study is to assess the incidence of congenital heart diseases and other organic defects associated with different types of orofacial clefts.

Methodology and Principal Findings

All children with orofacial clefts, which were sought out from the Health Information System of Shanghai Ninth People's Hospital between 1st Jan 2009 and 30th Dec 2011, were enrolled in this study. All subjects underwent a thorough examination and grouped by the cleft phenotype. The numbers and types of other organic defects were recorded and analyzed statistically using SPSS 17.0. Of 2180 cases reported as having orofacial clefts, 657 (30.1%) had other congenital abnormalities, which were significantly more common in cleft palate (47.9% (329/687)) than that in cleft lip (10.6% (80/755)) or cleft lip and palate (33.6% (248/738)) (P<0.01). In subgroups, unilateral cleft lip and palate had a statistically higher incidence of associated abnormalities than bilateral cleft lip and palate (P<0.01). The most common malformation was congenital heart disease, which counted 45.1% (296/657) of all malformations. Disorders of the central nervous system (14.3%(94/657)) and Skeletal anomalies (13.1%(86/657)) were also frequently associated. Additionally, the most common defect in heart was atrial septal defect, which was 39.7% (118/296) of all congenital heart diseases.

Conclusions and Significance

As the high incidence of heart defects and other organic abnormalities in the children with cleft palate in Eastern China, special attention should be paid to them and echocardiography should be a proposed examination in the evaluation of children with cleft palate before any surgical correction being executed.

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<![CDATA[Coordinately Co-opted Multiple Transposable Elements Constitute an Enhancer for wnt5a Expression in the Mammalian Secondary Palate]]> https://www.researchpad.co/article/5989da86ab0ee8fa60b9c68f

Acquisition of cis-regulatory elements is a major driving force of evolution, and there are several examples of developmental enhancers derived from transposable elements (TEs). However, it remains unclear whether one enhancer element could have been produced via cooperation among multiple, yet distinct, TEs during evolution. Here we show that an evolutionarily conserved genomic region named AS3_9 comprises three TEs (AmnSINE1, X6b_DNA and MER117), inserted side-by-side, and functions as a distal enhancer for wnt5a expression during morphogenesis of the mammalian secondary palate. Functional analysis of each TE revealed step-by-step retroposition/transposition and co-option together with acquisition of a binding site for Msx1 for its full enhancer function during mammalian evolution. The present study provides a new perspective suggesting that a huge variety of TEs, in combination, could have accelerated the diversity of cis-regulatory elements involved in morphological evolution.

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<![CDATA[Psychiatric Diagnoses in Individuals with Non-Syndromic Oral Clefts: A Danish Population-Based Cohort Study]]> https://www.researchpad.co/article/5989d9e1ab0ee8fa60b6979b

Background

The aim of this study was to investigate the risk of psychiatric diagnoses in individuals with non-syndromic oral clefts (OC) compared with individuals without OC, including ages from 1 to 76 years.

Methods

Linking four Danish nationwide registers, we investigated the risk of psychiatric diagnoses at Danish psychiatric hospitals during the period 1969–2012 for individuals born with non-syndromic OC in Denmark 1936–2009 compared with a cohort of 10 individuals without OC per individual with OC, matched by sex and birth year. The sample included 8,568 individuals with OC, observed for 247,821 person-years, and 85,653 individuals without OC followed for 2,501,129 person-years.

Results

A total of 953 (11.1%) of the individuals with OC (9.6% for cleft lip (CL), 10.8% for cleft lip and palate (CLP) and 13.1% for cleft palate (CP)) and 8,117 (9.5%) in the comparison group had at least one psychiatric diagnosis. Cox proportional hazard regression model revealed that individuals with OC had significantly higher risk of a psychiatric diagnosis (hazard ratio (HR) = 1.19, 95% CI: 1.12–1.28). When examining cleft type, no difference was found for CL (HR = 1.03, 95% CI: 0.90–1.17), but CLP was associated with a small increased risk (HR = 1.13, 95% CI: 1.01–1.26), whereas individuals with CP had the largest increased risk (HR = 1.45, 95% CI: 1.30–1.62). The largest differences were found in schizophrenia-like disorders, mental retardation and pervasive developmental disorders, but we found no increased risk of mood disorders and anxiety-related disorders.

Conclusion

Individuals with non-syndromic OC had significantly higher risk of psychiatric diagnoses compared with individuals without OC. However, the elevated risk was observed for individuals with CLP and CP but not for individuals with CL and the absolute risk increase was modest.

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<![CDATA[Methods to Quantify Soft-Tissue Based Facial Growth and Treatment Outcomes in Children: A Systematic Review]]> https://www.researchpad.co/article/5989dad7ab0ee8fa60bb895a

Context

Technological advancements have led craniofacial researchers and clinicians into the era of three-dimensional digital imaging for quantitative evaluation of craniofacial growth and treatment outcomes.

Objective

To give an overview of soft-tissue based methods for quantitative longitudinal assessment of facial dimensions in children until six years of age and to assess the reliability of these methods in studies with good methodological quality.

Data Source

PubMed, EMBASE, Cochrane Library, Web of Science, Scopus and CINAHL were searched. A hand search was performed to check for additional relevant studies.

Study Selection

Primary publications on facial growth and treatment outcomes in children younger than six years of age were included.

Data Extraction

Independent data extraction by two observers. A quality assessment instrument was used to determine the methodological quality. Methods, used in studies with good methodological quality, were assessed for reliability expressed as the magnitude of the measurement error and the correlation coefficient between repeated measurements.

Results

In total, 47 studies were included describing 4 methods: 2D x-ray cephalometry; 2D photography; anthropometry; 3D imaging techniques (surface laser scanning, stereophotogrammetry and cone beam computed tomography). In general the measurement error was below 1 mm and 1° and correlation coefficients range from 0.65 to 1.0.

Conclusion

Various methods have shown to be reliable. However, at present stereophotogrammetry seems to be the best 3D method for quantitative longitudinal assessment of facial dimensions in children until six years of age due to its millisecond fast image capture, archival capabilities, high resolution and no exposure to ionizing radiation.

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<![CDATA[Genetic Disruption of the Sh3pxd2a Gene Reveals an Essential Role in Mouse Development and the Existence of a Novel Isoform of Tks5]]> https://www.researchpad.co/article/5989d9e7ab0ee8fa60b6bbbf

Tks5 is a scaffold protein and Src substrate involved in cell migration and matrix degradation through its essential role in invadosome formation and function. We have previously described that Tks5 is fundamental for zebrafish neural crest cell migration in vivo. In the present study, we sought to investigate the function of Tks5 in mammalian development by analyzing mice mutant for sh3pxd2a, the gene encoding Tks5. Homozygous disruption of the sh3pxd2a gene by gene-trapping in mouse resulted in neonatal death and the presence of a complete cleft of the secondary palate. Interestingly, embryonic fibroblasts from homozygous gene-trap sh3pxd2a mice lacked only the highest molecular weight band of the characteristic Tks5 triplet observed in protein extracts, leaving the lower molecular weight bands unaffected. This finding, together with the existence of two human Expressed Sequence Tags lacking the first 5 exons of SH3PXD2A, made us hypothesize about the presence of a second alternative transcription start site located in intron V. We performed 5′RACE on mouse fibroblasts and isolated a new transcript of the sh3pxd2a gene encoding a novel Tks5 isoform, that we named Tks5β. This novel isoform diverges from the long form of Tks5 in that it lacks the PX-domain, which confers affinity for phosphatidylinositol-3,4-bisphosphate. Instead, Tks5β has a short unique amino terminal sequence encoded by the newly discovered exon 6β; this exon includes a start codon located 29 bp from the 5'-end of exon 6. Tks5β mRNA is expressed in MEFs and all mouse adult tissues analyzed. Tks5β is a substrate for the Src tyrosine kinase and its expression is regulated through the proteasome degradation pathway. Together, these findings indicate the essentiality of the larger Tks5 isoform for correct mammalian development and the transcriptional complexity of the sh3pxd2a gene.

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<![CDATA[The Ubiquitin E3 Ligase NOSIP Modulates Protein Phosphatase 2A Activity in Craniofacial Development]]> https://www.researchpad.co/article/5989da3eab0ee8fa60b88e38

Holoprosencephaly is a common developmental disorder in humans characterised by incomplete brain hemisphere separation and midface anomalies. The etiology of holoprosencephaly is heterogeneous with environmental and genetic causes, but for a majority of holoprosencephaly cases the genes associated with the pathogenesis could not be identified so far. Here we report the generation of knockout mice for the ubiquitin E3 ligase NOSIP. The loss of NOSIP in mice causes holoprosencephaly and facial anomalies including cleft lip/palate, cyclopia and facial midline clefting. By a mass spectrometry based protein interaction screen we identified NOSIP as a novel interaction partner of protein phosphatase PP2A. NOSIP mediates the monoubiquitination of the PP2A catalytic subunit and the loss of NOSIP results in an increase in PP2A activity in craniofacial tissue in NOSIP knockout mice. We conclude, that NOSIP is a critical modulator of brain and craniofacial development in mice and a candidate gene for holoprosencephaly in humans.

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<![CDATA[Three Dimensional Assessment of the Pharyngeal Airway in Individuals with Non-Syndromic Cleft Lip and Palate]]> https://www.researchpad.co/article/5989da72ab0ee8fa60b955c6

Introduction

Children with cleft lip and palate (CLP) are known to have airway problems. Previous studies have shown that individuals with CLP have a 30% reduction in nasal airway size compared to non-cleft controls. No reports have been found on cross-sectional area and volume of the pharyngeal airway in clefts. Introduction of Cone-Beam CT (CBCT) and imaging software has facilitated generation of 3D images for assessment of the cross-sectional area and volume of the airway.

Objective

To assess the pharyngeal airway in individuals with CLP using CBCT by measuring volume and smallest cross-sectional areas and compare with 19 age- and sex-matched non-cleft controls.

Methods

Retrospective study of CBCT data of pre-adolescent individuals (N = 19, Mean age = 10.6, 7 females, 12 males, UCLP = 6, BCLP = 3) from the Center for Craniofacial Anomalies. Volumetric analysis was performed using image segmentation features in CB Works 3.0. Volume and smallest cross-sectional were studied in both groups. Seven measurements were repeated to verify reliability using Pearson correlation coefficient. Volume and cross-sectional area differences were analyzed using paired t-tests.

Results

The method was found to be reliable. Individuals with CLP did not exhibit smaller total airway volume and cross sectional area than non-CLP controls.

Conclusion

3D imaging using CBCT and CB Works is reliable for assessing airway volume. Previous studies have shown that the nasal airway is restricted in individuals with CLP. In our study, we found that the pharyngeal airway is not compromised in these individuals.

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<![CDATA[Computer-Assisted Orthognathic Surgery for Patients with Cleft Lip/Palate: From Traditional Planning to Three-Dimensional Surgical Simulation]]> https://www.researchpad.co/article/5989da70ab0ee8fa60b94994

Background

Although conventional two-dimensional (2D) methods for orthognathic surgery planning are still popular, the use of three-dimensional (3D) simulation is steadily increasing. In facial asymmetry cases such as in cleft lip/palate patients, the additional information can dramatically improve planning accuracy and outcome. The purpose of this study is to investigate which parameters are changed most frequently in transferring a traditional 2D plan to 3D simulation, and what planning parameters can be better adjusted by this method.

Patients and Methods

This prospective study enrolled 30 consecutive patients with cleft lip and/or cleft palate (mean age 18.6±2.9 years, range 15 to 32 years). All patients received two-jaw single-splint orthognathic surgery. 2D orthodontic surgery plans were transferred into a 3D setting. Severe bony collisions in the ramus area after 2D plan transfer were noted. The position of the maxillo-mandibular complex was evaluated and eventually adjusted. Position changes of roll, midline, pitch, yaw, genioplasty and their frequency within the patient group were recorded as an alternation of the initial 2D plan. Patients were divided in groups of no change from the original 2D plan and changes in one, two, three and four of the aforementioned parameters as well as subgroups of unilateral, bilateral cleft lip/palate and isolated cleft palate cases. Postoperative OQLQ scores were obtained for 20 patients who finished orthodontic treatment.

Results

83.3% of 2D plans were modified, mostly concerning yaw (63.3%) and midline (36.7%) adjustments. Yaw adjustments had the highest mean values in total and in all subgroups. Severe bony collisions as a result of 2D planning were seen in 46.7% of patients. Possible asymmetry was regularly foreseen and corrected in the 3D simulation.

Conclusion

Based on our findings, 3D simulation renders important information for accurate planning in complex cleft lip/palate cases involving facial asymmetry that is regularly missed in conventional 2D planning.

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<![CDATA[Maternal Transmission Effect of a PDGF-C SNP on Nonsyndromic Cleft Lip with or without Palate from a Chinese Population]]> https://www.researchpad.co/article/5989da6fab0ee8fa60b9428f

Cleft lip with or without palate (CL/P) is a common congenital anomaly with a high birth prevalence in China. Based on a previous linkage signal of nonsyndromic CL/P (NSCL/P) on the chromosomal region 4q31–q32 from the Chinese populations, we screened the 4q31–q32 region for susceptibility genes in 214 trios of Han Chinese. PDGF-C, an important developmental factor, resides in the region and has been implicated in NSCL/P. However, in our family-based association test (transmission disequilibrium test; TDT), we could not conclude an association between PDGF-C and NSCL/P as previously suggested. Instead, we found strong evidence for parent-of-origin effect at a PDGF-C SNP, rs17035464, by a likelihood ratio test (unadjusted p-value = 0.0018; Im = 2.46). The location of rs17035464 is 13 kb downstream of a previously reported, NSCL/P-associated SNP, rs28999109. Furthermore, a patient from our sample trios was observed with a maternal segmental uniparental isodisomy (UPD) in a region containing rs17035464. Our findings support the involvement of PDGF-C in the development of oral clefts; moreover, the UPD case report contributes to the collective knowledge of rare variants in the human genome.

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<![CDATA[Economic Analysis of Children’s Surgical Care in Low- and Middle-Income Countries: A Systematic Review and Analysis]]> https://www.researchpad.co/article/5989da1aab0ee8fa60b7c717

Background

Understanding the economic value of health interventions is essential for policy makers to make informed resource allocation decisions. The objective of this systematic review was to summarize available information on the economic impact of children’s surgical care in low- and middle-income countries (LMICs).

Methods

We searched MEDLINE (Pubmed), Embase, and Web of Science for relevant articles published between Jan. 1996 and Jan. 2015. We summarized reported cost information for individual interventions by country, including all costs, disability weights, health outcome measurements (most commonly disability-adjusted life years [DALYs] averted) and cost-effectiveness ratios (CERs). We calculated median CER as well as societal economic benefits (using a human capital approach) by procedure group across all studies. The methodological quality of each article was assessed using the Drummond checklist and the overall quality of evidence was summarized using a scale adapted from the Agency for Healthcare Research and Quality.

Findings

We identified 86 articles that met inclusion criteria, spanning 36 groups of surgical interventions. The procedure group with the lowest median CER was inguinal hernia repair ($15/DALY). The procedure group with the highest median societal economic benefit was neurosurgical procedures ($58,977). We found a wide range of study quality, with only 35% of studies having a Drummond score ≥ 7.

Interpretation

Our findings show that many areas of children’s surgical care are extremely cost-effective in LMICs, provide substantial societal benefits, and are an appropriate target for enhanced investment. Several areas, including inguinal hernia repair, trichiasis surgery, cleft lip and palate repair, circumcision, congenital heart surgery and orthopedic procedures, should be considered “Essential Pediatric Surgical Procedures” as they offer considerable economic value. However, there are major gaps in existing research quality and methodology which limit our current understanding of the economic value of surgical care.

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<![CDATA[Stress-Coping and Cortisol Analysis in Patients with Non-Syndromic Cleft Lip and Palate: An Explorative Study]]> https://www.researchpad.co/article/5989daa0ab0ee8fa60ba5722

Background

Non-syndromic clefts of the orofacial region occur in approximately 1 per 500 to 2,500 live births, depending on geographical area and ethnicity. It can be supposed that the disruption of the normal facial structure and the long-standing pressure of treatment from birth to adulthood bring about a range of life stressors which may lead to a long-lasting impact on affected subjects throughout their lives. Therefore, the present study aimed to assess different aspects of psychosocial stress in affected individuals.

Methods

The study was divided into two parts: first, the Trier Social Stress Test which involves uncontrollability and high levels of social-evaluative stress under real conditions and second, the query of various aspects of coping with psychosocial stress. The test group consisted of 30 affected adult subjects, and an equally sized control group of unaffected volunteers. Cortisol dysregulation was determined by saliva samples before and after stress induction. Meanwhile, participants were asked to complete the SVF 120 stress-coping questionnaire.

Results

The analysis of saliva samples showed a similar baseline concentration as well as a similar increase in cortisol levels after stress induction for both groups. Subsequently, the decline in cortisol concentrations was significantly faster in the CLP group (course: p<0.001; groups: p = 0.102; interaction: p = 0.167). The evaluation of the stress-coping questionnaire revealed a significantly shorter rumination about a stressful event in individuals with CLP-related malformations (p = 0.03).

Conclusion

We conclude that adults with CLP have significantly better stress-coping strategies than their healthy peers.

Trial Registration

German Clinical Trials Organization DRKS00003466

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<![CDATA[Neighborhood Deprivation and Risk of Congenital Heart Defects, Neural Tube Defects and Orofacial Clefts: A Systematic Review and Meta-Analysis]]> https://www.researchpad.co/article/5989da16ab0ee8fa60b7b3bf

Background

We conducted this systematic review and meta-analysis to address the open question of a possible association between the socioeconomic level of the neighborhoods in which pregnant women live and the risk of Congenital Heart Defects (CHDs), Neural Tube Defects (NTDs) and OroFacial Clefts (OFCs).

Methods

We searched MEDLINE from its inception to December 20th, 2015 for case-control, cohort and ecological studies assessing the association between neighborhood socioeconomic level and the risk of CHDs, NTDs and the specific phenotypes Cleft Lip with or without Cleft Palate (CLP) and Cleft Palate (CP). Study-specific risk estimates were pooled according to random-effect and fixed-effect models.

Results

Out of 245 references, a total of seven case-control studies, two cohort studies and two ecological studies were assessed in the systematic review; all studies were enrolled in the meta-analysis with the exception of the two cohort studies. No significant association has been revealed between CHDs or NTDs and neighborhood deprivation index. For CLP phenotype subgroups, we found a significantly higher rate in deprived neighborhoods (Odds Ratios (OR) = 1.22, 95% CI: 1.10, 1.36) whereas this was not significant for CP phenotype subgroups (OR = 1.20, 95%CI: 0.89, 1.61).

Conclusion

In spite of the small number of epidemiological studies included in the present literature review, our findings suggest that neighborhood socioeconomic level where mothers live is associated only with an increased risk of CLP phenotype subgroups. This finding has methodological limitations that impede the formulation of firm conclusions, and further investigations should confirm this association.

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