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OBJECTIVES: This investigation aimed to assess the optimal timing for lip repair in children with cleft lip and palate via 3D anthropometric analysis to evaluate their maxillofacial structures. METHODS: The sample comprised 252 digitized dental models, divided into groups according to the following timing of lip repair: G1 (n = 50): 3 months; G2 (n = 50): 5 and 6 months; G3 (n = 26): 8 and 10 months. Models were evaluated at two-time points: T1: before lip repair; T2: at 5 years of age. Linear measurements, area, and Atack index were analyzed. RESULTS: At T1, the intergroup analysis revealed that G1 had statistically significant lower means of I-C', I-C, C-C', and the sum of the segment areas compared to G2 (p = 0.0140, p = 0.0082, p = 0.0004, p < 0.0001, respectively). In addition, there was a statistically significant difference when comparing the cleft area between G2 and G3 (p = 0.0346). At T2, the intergroup analysis revealed that G1 presented a statistically significant mean I-C' compared to G3 (p = 0.0461). In the I-CC' length analysis, G1 and G3 showed higher means when compared to G2 (p = 0.0039). The I-T' measurement was statistically higher in G1 than in G2 (p = 0.0251). In the intergroup growth rate analysis, G1 and G2 showed statistically significant differences in the I-C' measurement compared to G3 (p = 0.0003). In the analysis of the Atack index, there was a statistically significant difference between G1 and the other sample sets (p < 0.0001). CONCLUSION: Children who underwent surgery later showed better results in terms of the growth and development of the dental arches.
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BACKGROUND: Premutations in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene, defined as between 55 and 200 CGGs, have been implicated in fragile X-associated primary ovarian insufficiency (FXPOI). Only 20% of female premutation carriers develop early ovulatory dysfunction, the reason for this incomplete penetrance is unknown. This study validated the mathematical model in premutation alleles, after assigning each allele a score representing allelic complexity. Subsequently, allelic scores were used to investigate the impact of allele complexity on age at amenorrhea for 58 premutation cases (116 alleles) previously published. METHODS: The allelic score was determined using a formula previously described by our group. The impact of each allelic score on age at amenorrhea was analyzed using Pearson's test and a contour plot generated to visualize the effect. RESULTS: Correlation of allelic score revealed two distinct complexity behaviors in premutation alleles. No significant correlation was observed between the allelic score of premutation alleles and age at amenorrhea. The same lack of significant correlation was observed regarding normal-sized alleles, despite a nearly significant trend. CONCLUSIONS: Our results suggest that the use of allelic scores combination have the potential to explain female infertility, namely the development of FXPOI, or ovarian dysfunction, despite the lack of correlation with age at amenorrhea. Such a finding is of great clinical significance for early identification of females at risk of ovulatory dysfunction, enhancement of fertility preservation techniques, and increasing the probability for a successful pregnancy in females with premutations. Additional investigation is necessary to validate this hypothesis.
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Alelos , Amenorrea , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Insuficiencia Ovárica Primaria , Humanos , Femenino , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Amenorrea/genética , Insuficiencia Ovárica Primaria/genética , Adulto , Heterocigoto , Mutación , Síndrome del Cromosoma X Frágil/genética , Factores de Edad , Adulto Joven , AdolescenteRESUMEN
Aim: This study aimed to investigate the occurrence of enamelin gene (ENAM) single nucleotide polymorphisms (SNP) and ENAM polymorphism association with dental anomalies (DA) in individuals with unilateral or bilateral cleft lip and palate (CLP). Methods: Saliva samples were collected from 147 individuals aged between 6 and 15 years-old, both genders, and divided into 4 groups: Group 1 (G1) - CLP and DA; Group 2 (G2) - CLP without DA; Group 3 (G3) - without CLP with DA; Group 4 (G4) - without CLP and DA. The genomic DNA was extracted from saliva samples and the following ENAM SNPs markers were genotyped: rs3796703, rs3796704, rs3796705, rs7671281, rs2609428, and rs35951442. Fisher exact and Pearson's Chi-square tests statistically analyzed the results (α=5%). Results: Individuals without CLP with DA (Group 3 - 19.2%) showed statistically higher prevalence of SNP rs2609428 heterozygotes (p=0.006) than individuals with CLP and DA (Group 1 - 0%). Individuals without CLP (10%) exhibited statistically higher prevalence of mutated heterozygotes/homozygous (p=0.028) than in individuals with CLP (1.3%). Conclusion: SNP rs2609428 marker of ENAM gene may be associated with dental anomalies in individuals without cleft lip and palate
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Humanos , Masculino , Femenino , Niño , Adolescente , Anomalías Dentarias , Proteínas de la Matriz Extracelular , Labio Leporino , Fisura del Paladar , Polimorfismo de Nucleótido SimpleRESUMEN
ABSTRACT Objective: To evaluate the clinical and radiographic response of pulp-dentin complex after selective caries removal with or without pulp lining in primary teeth. Material and Methods: Twenty-four primary molars with deep occlusal caries lesions and without pulpal alterations were selected from children, both genders, aged between 5 and 9 years old. After selective caries removal, the teeth were divided into three groups: without cavity liner (Group I), calcium hydroxide cement - CH (Group II), and Mineral trioxide aggregate - MTA (Group III). The final restoration was performed with resin-modified glass ionomer cement. Clinical and radiographic assessments were conducted at 6-month follow-up. The Kappa test determined intraexaminer reliability. Fisher's exact test evaluated intergroup comparisons (p<0.05). Results: All teeth showed clinical and radiographic success at the 6-month follow-up without statistically significant differences (p>0.05). Conclusion: Selective caries removal without cavity lining was acceptable for deep caries lesions in primary teeth.
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Humanos , Masculino , Femenino , Preescolar , Niño , Diente Primario , Radiografía Dental/instrumentación , Caries Dental/prevención & control , Recubrimiento de la Pulpa Dental , Interpretación Estadística de DatosRESUMEN
Objetivo: Avaliar a aceitabilidade e o conhecimento de estudantes de graduação em Odontologia e cirurgiões-dentistas sobre a remoção seletiva de tecido cariado (RSTC). Materiais e Métodos: Participaram do estudo graduandos do terceiro e quarto ano de Odontologia (Grupo 1) e egressos de um Centro Hospitalar de Odontologia (Grupo 2). Os participantes responderam de forma anônima e confidencial um questionário validado contendo onze questões sobre diagnóstico e manejo de lesões cariosas profundas. Teste qui-quadrado de Pearson e regressão logística multivariada foram aplicados (p<0.05). Resultados: A amostra total foi composta por 146 participantes. Destes, 81.5% eram do sexo feminino; 52.05% eram graduados e a faixa etária mais prevalente foi de 18 a 29 anos (85.62%). Sessenta e nove participantes escolheram o tratamento expectante (p=0.027). A análise de regressão logística mostrou diferenças estatisticamente significativas. Os participantes que consideraram a parede pulpar úmida têm aproximadamente oito vezes mais chances de escolha pelo tratamento invasivo (p=0.028). Aqueles que escolheram o tratamento endodôntico como opção de sobrevida em dois anos têm três vezes mais chances de optar pelo tratamento invasivo (p=0.032). Aqueles que afirmaram que a dentina cariada próxima à polpa não deveria ser removida tiveram quase três vezes mais chances de optar por tratamentos minimamente invasivos (p=0.031). Discussão: Estudos com questionários podem ser ferramentas úteis para detectar se estudantes e cirurgiões-dentistas estão seguindo as evidências mais atuais para o tratamento de lesões cariosas profundas. Conclusão: Os participantes tinham certo nível de conhecimento sobre RSTC, mas a aceitabilidade da técnica carecia de consenso.
Aim: The aim of this study was to evaluate the acceptability and knowledge of undergraduate dental students and dentists on selective caries tissue removal (SCTR). Materials and Methods: Third- and fourth-year Dentistry undergraduates (Group 1) and graduates working in a Hospital Dentistry Center (Group 2) were included in the study. Participants anonymously and confidentially answered a validated questionnaire containing eleven questions on the diagnosis and management of deep caries lesions. Pearson's Chi-square test and multivariate logistic regression compared the answers (p<0.05). Results: Total sample comprised 146 participants. Of these, 81.5% were female; 52.05% were graduates and the most prevalent age group was 18-29 years old (85.62%). Sixty-nine participants chose stepwise caries removal (p=0.027). The logistic regression analysis showed statistically significant differences. The participants who considered pulp wall moist have approximately eight times more likelihood to choose an invasive treatment (p=0.028). Those who chose endodontic treatment as an option for two-year survival have three times more likelihood to choose an invasive treatment (p=0.032). Those who affirmed that the carious dentin close to the pulp should not be removed had almost three times more likelihood to choose minimally invasive treatments (p=0.031). Discussion: Studies with questionnaires can be useful tools to detect whether the students and dentists are following the most current evidences to treat deep carious lesions. Conclusion: The participants had certain level of knowledge on SCTR, but the technique acceptability lacked consensus.
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This study aimed to evaluate the postsurgical effects from 5 years on the palate after surgical repair of the lip at 3 or 9 months of age in children with cleft lip and palate. Eighty-four digitized dental impressions were divided into the following groups: group 1 (G1): lip surgery at 3 months of life; group 2 (G2): lip surgery at 9 months of life; group 3 (G3): without orofacial cleft. Five angular (C'IC, ICM, IC'M', CMM', and C'M'M) and 3 linear parameters (C-C', c-c', and M-M') were evaluated. Statistical analysis was applied with α=5%. Intraclass Correlation Coefficient was significantly smaller in G1 than in G3 ( P =0.005), while IC'M' was significantly smaller in G3 than in G1 ( P <0.001). C'M'M was significantly smaller in G1 than in G2 and G3 ( P <0.001). The distances C-C' and c-c' were significantly smaller in G1 than in G2 and G3 ( P <0.001). There was a statistically significant difference in both G1 and G2 ( P <0.001, in all) in the analysis of palatal symmetry. Linear regression analysis showed that the, 11.2% of outcomes determined by c-c' distance can be explained by the age of lip repair ( P =0.013). In conclusion, lip surgery at 3 months of life showed a tendency toward more restriction in 5-year postsurgery palate development. The age of cheiloplasty is one of the factors that can influence palatal development; however, other factors may be associated and should be studied.
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Labio Leporino , Fisura del Paladar , Niño , Humanos , Preescolar , Labio Leporino/cirugía , Fisura del Paladar/cirugía , Estudios Transversales , Maxilar/cirugía , Arco DentalRESUMEN
Orofacial clefts are the most prevalent craniofacial congenital anomalies, affecting the lip, with or without involvement of the palate, or solely the palate [...].
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The assessment of rehabilitation outcomes requires a patient documentation protocol, including records obtained at standardized ages, to compare different types of surgeries, their effects, as well as between different rehabilitation centers. The aim of this paper was to present proper trays for babies with different types of cleft lip and palate, which are used in the outpatient routine at Hospital of Rehabilitation of Craniofacial Anomalies/USP (HRAC/USP). The customized trays are made with self-curing acrylic resin. The tray must have suitable depth to copy the buccal sulcus, and wax is usually applied to contour the tray edge, and the adjustment of the tray to the fornix, making the tray specific for each child. The impression precludes the utilization of dental casts for diagnosis, treatment plan, and research measurements. In the clinical practice at HRAC-USP, it was observed that customized trays increased the quality of impression, accurately reproducing anatomical features of dental arches of babies with oral clefts.
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Labio Leporino , Fisura del Paladar , Niño , Humanos , Labio Leporino/cirugía , Labio Leporino/rehabilitación , Fisura del Paladar/cirugía , Fisura del Paladar/rehabilitación , Técnica de Impresión Dental , Resultado del TratamientoRESUMEN
We describe the phenotype of 22 male patients (20 probands) carrying a hemizygous missense variant in MED12. The phenotypic spectrum is very broad ranging from nonspecific intellectual disability (ID) to the three well-known syndromes: Opitz-Kaveggia syndrome, Lujan-Fryns syndrome, or Ohdo syndrome. The identified variants were randomly distributed throughout the gene (p = 0.993, χ2 test), but mostly outside the functional domains (p = 0.004; χ2 test). Statistical analyses did not show a correlation between the MED12-related phenotypes and the locations of the variants (p = 0.295; Pearson correlation), nor the protein domain involved (p = 0.422; Pearson correlation). In conclusion, establishing a genotype-phenotype correlation in MED12-related diseases remains challenging. Therefore, we think that patients with a causative MED12 variant are currently underdiagnosed due to the broad patients' clinical presentations.
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Blefarofimosis , Discapacidad Intelectual , Discapacidad Intelectual Ligada al Cromosoma X , Masculino , Humanos , Complejo Mediador/genética , Discapacidad Intelectual Ligada al Cromosoma X/genética , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Blefarofimosis/genética , Mutación Missense/genética , Fenotipo , SíndromeRESUMEN
Craniofacial development begins during the fourth week of intrauterine life (IUL) [...].
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Aim: to evaluate the surgical effects of two rehabilitation protocols on dental arch occlusion of 5-year-old children with or without cleft lip and palate. Methods: this is a retrospective longitudinal study the sample comprised 45 digitized dental casts divided into followed groups: Group 1 (G1) children who underwent to cheiloplasty (Millard technique) at 3 months and to one-stage palatoplasty (von Langenbeck technique) at 12 months; Group 2 (G2) children who underwent to cheiloplasty (Millard technique) and two-stage palatoplasty (Hans Pichler technique for hard palate closure) at 3 months and at 12 months to soft palate closure (Sommerlad technique); and Group 3 (G3) children without craniofacial anomalies. Linear measurements, area, and occlusion were evaluated by stereophotogrammetry software. Shapiro-Wilk test was used to verify normality. ANOVA followed by posthoc Tukey test and Kruskal-Wallis followed by posthoc Dunn tests were used to compared groups. Results: For the measures intercanine distance (C-C'), anterior length of dental arch (I-CC'), and total length of the dental arch (IMM'), there were statistical differences between G1x G3 and G2xG3, the mean was smaller for G1 and G2. No statistically significant differences occurred in the intermolar distance and in the dental arch area among groups. The occlusion analysis revealed significant difference in the comparison of the three groups (p=0.0004). Conclusion: The surgical effects of two rehabilitation protocols affected the occlusion and the development of the anterior region of the maxilla of children with oral clefts when compared to children without oral clefts.
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Humanos , Masculino , Femenino , Preescolar , Niño , Cirugía Bucal , Protocolos Clínicos , Labio Leporino , Fisura del Paladar , Arco Dental , Oclusión DentalRESUMEN
BACKGROUND: It is necessary to analyze and monitor the facial growth of orofacial cleft patients. The documentation should therefore begin before and after primary surgeries. Technological evolution has transformed plaster models into 3D images through scanners that allow rational storage, manipulation, and rotation without the possibility of breakage or damage. Based on this fact, this narrative review aims to provide a feature on the three-dimensional tools available for the assessment of dental arches in children with orofacial cleft and mixed dentition. MATERIAL AND METHODS: Three databases were chosen (PubMed, ScienceDirect, and Scopus) and keywords were used to select papers. RESULTS: During the database screening, 292 potentially relevant papers were found. After removing duplicates, titles, and abstracts, 32 papers presented qualifications for analysis. Through evaluating each document by reading it one by one, 24 papers fulfilled the eligibility criteria. CONCLUSIONS: It was concluded that digital tools-i.e., benchtop scanners which evaluate the dental arches of children with cleft lip, palate, and mixed dentition-are reproducible and reliable, without the use of ionizing radiation, allow storage, manipulation with sustainability, and help preserve the environment.
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Ritscher-Schinzel syndrome (RTSCS) is a rare genetic condition characterized by peculiar craniofacial features and cerebellar and cardiovascular malformations. To date, four genes are implicated in this condition. The first two genes described were the autosomal recessive inherited gene WASHC5 associated with Ritscher-Schinzel syndrome 1 (RTSCS1), and CCDC22, an X-linked recessive gene causing Ritscher-Schinzel syndrome 2 (RTSCS2). In recent years, two other genes have been identified: VPS35L (RTSCS3) and DPYSL5 (RTSCS4). Only few patients with a molecular diagnosis of RTSCS have been reported, leaving the phenotypical spectrum and genotype-phenotype correlations ill-defined. We expand the number of genetically confirmed patients with RTSCS1 and 2; reporting three live born and three terminated pregnancies from two unrelated families. Four siblings carried compound heterozygous variants in WASHC5 while two siblings harboured a hemizygous CCDC22 variant. The most common findings in all patients were craniofacial dysmorphism, particularly macrocephaly, down slanted palpebral fissures and low set-ears. Developmental delay, intellectual disability and ataxic gait were present in all patients. One of the patients with the CCDC22 variant presented pubertas tarda. Elevation of nuchal translucency was observed in the first trimester ultrasound in three foetuses with compound heterozygous variants in WASHC5. None of the patients had epilepsy. The pre- and postnatal findings of this cohort expand the known phenotype of RTSCS1 and 2, with direct impact on postnatal outcome, management, and familial counseling.
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Anomalías Craneofaciales , Síndrome de Dandy-Walker , Femenino , Humanos , Embarazo , Anomalías Múltiples , Anomalías Craneofaciales/genética , Síndrome de Dandy-Walker/genética , Defectos del Tabique Interatrial , Hidrolasas/genética , Proteínas Asociadas a Microtúbulos/genética , Fenotipo , Proteínas/genética , SíndromeRESUMEN
OBJECTIVE: Oral cleft surgical repairs are performed using different techniques worldwide. To evaluate and compare the development of the dental arches of children with unilateral cleft lip and palate before and after the primary surgeries performed with different techniques at the first months and six years of life. METHODOLOGY: This is a retrospective longitudinal study. The sample comprised 56 dental casts divided int the following groups: Group 1 (G1) - cheiloplasty (Millard technique) at three months and one-step palatoplasty (von Langenbeck technique) at 12 months; and Group 2 (G2) - cheiloplasty (Millard technique) and two-step palatoplasty: anterior hard palate closure (Hans Pichler technique) at three months and posterior soft palate closure (Sommerlad technique) at 12 months. The digitized dental casts were evaluated at three months - pre-surgical (T1) and six years of life- post-surgical (T2). The following linear measurements were analyzed: intercanine (C-C'), intertuberosity (T-T') distances; anterior dental arch (I-CC'), anterior intersegment (I-C'), and total arch (I-TT') lengths. The palate area was also measured. Parametric and non-parametric tests were applied (p<0.05). RESULTS: In G1, the intragroup comparison showed statistically significant smaller I-CC' and I-C' at T2 (p=0.001 and p<0.001, respectively), while T-T', I-TT', and area comparisons were significantly greater (p<0.001, p=0.002, and p<0.001, respectively). In G2, the intragroup comparison exhibited statistically significant smaller C-C' and I-C' at T2 (p=0.004, for both), whereas T-T', I-TT' and area comparisons were significantly greater (p<0.001, p=0.004, and p<0.001, respectively). At T2, the intergroup analysis revealed that G1 had a statistically significant smaller I-CC' (p=0.014). The analysis of the intergroup differences (∆=T2-T1) showed that G1 had a statistically smaller I-CC' (p=0.043). CONCLUSION: The two-step palatoplasty showed a more favorable prognosis for the maxillary growth than one-step palatoplasty in children with oral clefts.
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Labio Leporino , Fisura del Paladar , Niño , Labio Leporino/cirugía , Fisura del Paladar/cirugía , Protocolos Clínicos , Arco Dental/cirugía , Humanos , Estudios Longitudinales , Maxilar/cirugía , Estudios RetrospectivosRESUMEN
This study describes the preparation, characterization, and antimicrobial properties of novel hybrid biopolymer materials doped with bioactive silver(I) coordination polymers (bioCPs). Two new bioCPs, [Ag2(µ6-hfa)]n (1) and [Ag2(µ4-nda)(H2O)2]n (2), were assembled from Ag2O and homophthalic (H2hfa) or 2,6-naphthalenedicarboxylic (H2nda) acids as unexplored building blocks. Their structures feature 2D metal-organic and supramolecular networks with 3,6L64 or sql topology. Both compounds act as active antimicrobial agents for producing bioCP-doped biopolymer films based on epoxidized soybean oil acrylate (SBO) or potato starch (PS) as model biopolymer materials with a different rate of degradability and silver release. BioCPs and their hybrid biopolymer films (1@[SBO]n, 2@[SBO]n, 1@[PS]n, and 2@[PS]n) with a very low loading of coordination polymer (0.05-0.5 wt %) show remarkable antimicrobial activity against Staphylococcus aureus and Staphylococcus epidermidis (Gram-positive) and Escherichia coli and Pseudomonas aeruginosa (Gram-negative) bacteria. Biopolymer films also effectively impair the formation of bacterial biofilms, allowing total biofilm inhibition in several cases. By reporting on new bioCPs and biopolymer films obtained from renewable biofeedstocks (soybean oil and PS), this study blends highly important research directions and widens a limited antimicrobial application of bioCPs and derived functional materials. This research thus opens up the perspectives for designing hybrid biopolymer films with outstanding bioactivity against bacterial biofilms.
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Antiinfecciosos , Solanum tuberosum , Antibacterianos/química , Antibacterianos/farmacología , Antiinfecciosos/farmacología , Biopelículas , Escherichia coli , Bacterias Gramnegativas , Pruebas de Sensibilidad Microbiana , Polímeros/química , Polímeros/farmacología , Plata/química , Plata/farmacología , Aceite de Soja , Staphylococcus epidermidis , Almidón/farmacologíaRESUMEN
X-chromosome inactivation (XCI) is a developmental process to compensate the imbalance in the dosage of X-chromosomal genes in females. A skewing of the XCI pattern may suggest a carrier status for an X-linked disease or explain the presence of a severe phenotype. In these cases, it is important to determine the XCI pattern, conventionally using the gold standard Human Androgen-Receptor Assay (HUMARA), based on the analysis of the methylation status at a polymorphic CAG region in the first exon of the human androgen receptor gene (AR). The aim of this study was to evaluate whether the methylation status of the fragile mental retardation protein translational regulator gene (FMR1) can provide an XCI pattern similar to that obtained by HUMARA. A set of 48 female carriers of FMR1 gene normal-sized alleles was examined using two assays: HUMARA and a FMR1 methylation PCR (mPCR). Ranges were defined to establish the XCI pattern using the methylation pattern of the FMR1 gene by mPCR. Overall, a 77% concordance of the XCI patterns was obtained between the two assays, which led us to propose a set of key points and a stepwise analysis towards obtaining an accurate result for the XCI pattern and to minimize the underlying pitfalls.
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Metilación de ADN , Inactivación del Cromosoma X , Animales , Cromosomas , Metilación de ADN/genética , Femenino , Heterocigoto , Masculino , Fenotipo , Inactivación del Cromosoma X/genéticaRESUMEN
This study evaluated the palatal surface area in children with different oral clefts after primary surgeries and at five years of age. This longitudinal study was composed by 216 digital models: unilateral complete cleft lip (UCL), unilateral complete cleft lip and palate (UCLP), and complete cleft palate (CP). The models were analysed at four time periods: T1 (before cheiloplasty), T2 (before palatoplasty), T3 (after palatoplasty); and T4 - (at five years of age). Area of the dental arches was measured through stereophotogrammetry software. Measurements evaluated with Student's test and ANOVA followed by the Tukey test (p<0.05) (AQ 1). In the UCL group, the palatal surface area significantly increased among phases. In the primary surgery periods, UCLP and CP significantly decreased (p<0.001). Palatal area in the UCLP group was significantly greater than the CP group. Overall, no statistically significant differences occurred among groups. At T4, the area of the palate in the UCL group was significantly greater than the UCLP group and no significant differences occurred between UCLP and CP groups. This study suggests that cheiloplasty did not inhibit the growth of the palatal surface area in children with UCL and UCLP. Palatoplasty significantly decreased the palatal area in children with UCLP and CP, demonstrating a significant negative effect of palatal repair on maxillary growth. At five years, children with UCLP and CP had a significantly smaller palate area than those with UCL.
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Labio Leporino , Fisura del Paladar , Niño , Labio Leporino/cirugía , Fisura del Paladar/cirugía , Arco Dental/cirugía , Humanos , Estudios Longitudinales , Maxilar/cirugíaRESUMEN
Free oligosaccharides (fOSs) are soluble oligosaccharide species generated during N-glycosylation of proteins. Although little is known about fOS metabolism, the recent identification of NGLY1 deficiency, a congenital disorder of deglycosylation (CDDG) caused by loss of function of an enzyme involved in fOS metabolism, has elicited increased interest in fOS processing. The catabolism of fOSs has been linked to the activity of a specific cytosolic mannosidase, MAN2C1, which cleaves α1,2-, α1,3-, and α1,6-mannose residues. In this study, we report the clinical, biochemical, and molecular features of six individuals, including two fetuses, with bi-allelic pathogenic variants in MAN2C1; the individuals are from four different families. These individuals exhibit dysmorphic facial features, congenital anomalies such as tongue hamartoma, variable degrees of intellectual disability, and brain anomalies including polymicrogyria, interhemispheric cysts, hypothalamic hamartoma, callosal anomalies, and hypoplasia of brainstem and cerebellar vermis. Complementation experiments with isogenic MAN2C1-KO HAP1 cells confirm the pathogenicity of three of the identified MAN2C1 variants. We further demonstrate that MAN2C1 variants lead to accumulation and delay in the processing of fOSs in proband-derived cells. These results emphasize the involvement of MAN2C1 in human neurodevelopmental disease and the importance of fOS catabolism.
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Quistes del Sistema Nervioso Central/genética , Trastornos Congénitos de Glicosilación/genética , Hamartoma/genética , Discapacidad Intelectual/genética , Oligosacáridos/metabolismo , Péptido-N4-(N-acetil-beta-glucosaminil) Asparagina Amidasa/deficiencia , Polimicrogiria/genética , alfa-Manosidasa/genética , Adolescente , Alelos , Tronco Encefálico/metabolismo , Tronco Encefálico/patología , Línea Celular Tumoral , Quistes del Sistema Nervioso Central/metabolismo , Quistes del Sistema Nervioso Central/patología , Vermis Cerebeloso/metabolismo , Vermis Cerebeloso/patología , Niño , Preescolar , Trastornos Congénitos de Glicosilación/metabolismo , Trastornos Congénitos de Glicosilación/patología , Femenino , Feto , Glicosilación , Hamartoma/metabolismo , Hamartoma/patología , Humanos , Hipotálamo/metabolismo , Hipotálamo/patología , Discapacidad Intelectual/metabolismo , Discapacidad Intelectual/patología , Leucocitos/metabolismo , Leucocitos/patología , Masculino , Manosa/metabolismo , Péptido-N4-(N-acetil-beta-glucosaminil) Asparagina Amidasa/genética , Péptido-N4-(N-acetil-beta-glucosaminil) Asparagina Amidasa/metabolismo , Polimicrogiria/metabolismo , Polimicrogiria/patología , Lengua/metabolismo , Lengua/patología , alfa-Manosidasa/deficienciaRESUMEN
OBJECTIVES: This study aimed to compare dimensional alterations of dental arches in children with unilateral complete cleft lip and palate before and after different techniques of primary plastic surgeries. MATERIALS AND METHODS: The sample was divided into two groups: group 1-cheiloplasty by Millard's technique and one-stage palatoplasty by von Langenbeck's technique; group 2-cheiloplasty by Millard's technique and two-stage palatoplasty: anterior palatoplasty by Hans Pichler's technique and posterior palatoplasty by Sommerlad's technique. Dental arches were evaluated before (T1), after the first phase (T2), and 1 year after the second phase (T3) of primary surgeries. Linear measurements and palatal area were assessed. To analyze the method's error, interclass correlation coefficient was applied. ANOVA (followed by Tukey test), dependent, and independent t-test were used (p < 0.05). RESULTS: At T1, the intertuberosity distance was statistically greater in G2 (p = 0.004). At T2, the anterior length of the dental arch was statistically greater in G2 (p = 0.025), while the area of the smaller palatal segment (p = 0.001), cleft area (p = 0.014), and total area (p = 0.002) were statistically smaller in G2. At T3, the intertuberosity distance was statistically greater in G2 (p = 0.017). CONCLUSION: This study suggests that cheiloplasty and one-stage palatoplasty resulted in smaller growth of maxilla than cheiloplasty and two-stage palatoplasty in the linear measurements (T-T' and I-CC') and total area of the dental arches. CLINICAL RELEVANCE: Surgical protocols need to be evaluated to verify their effects aiming at improving the clinical practice of the interdisciplinary team, determining new parameters for the rehabilitation of individuals with cleft lip and palate.