PEMT variants are associated with nonsyndromic cleft lip with or without cleft palate in Chile.

Aim: To assess the association between PEMT variants and nonsyndromic cleft lip with or without cleft palate in Chile and the effects of these variants on global DNA methylation. Subjects & methods: The authors obtained genotypes for nine variants from 247 cases and 453 controls for genotype-phenotype associations. The effect of significant polymorphisms on global DNA methylation (percentage of long interspersed element-1 methylation) was evaluated in a subsample of 95 controls. Results: After multiple comparison corrections, variants rs7649 and rs4646409 were associated with nonsyndromic cleft lip with or without cleft palate. Carriers of risk alleles presented lower DNA methylation levels than noncarriers. Conclusion: According to functional analysis for risk variants from previous reports, the authors infer that a decrease of methyl group availability is occurring in affected subjects.

This study evaluated if variants in the gene named PEMT confers an increased risk for nonsyndromic cleft lip with or without cleft palate in Chile and its possible effects on methylation of DNA, a variable linked to gene expression modulation. The study found that the variants recognized as rs7649 and rs4646409 increase the risk of nonsyndromic cleft lip with or without cleft palate in the Chilean population and decrease DNA methylation. The authors conclude that this gene may be involved in this birth defect. New studies are needed to confirm the relation between this condition and DNA methylation mediated by these genetic variants.

Vitamin B12 Transport Genes and Nonsyndromic Cleft Lip With or Without Cleft Palate in Chile.

The aims of this study were to assess the association between polymorphisms within genes involved in vitamin B12 transport and nonsyndromic cleft lip with or without cleft palate (NSCL/P) and global DNA methylation in Chile. From 247 cases and 453 controls, we obtained variant genotypes for CBLIF, CUBN, AMN, ABCC1, CD320, and TCN2 from a single nucleotide polymorphisms array. Global DNA methylation in 95 controls was obtained through LINE-1 methylation. After multiple comparison corrections, only rs780807 in CUBN remains associated with NSCL/P at dominant model (OR 0.564, p-value = 0.0006, q-value = 0.0450). Carriers of protective allele showed lower levels of DNA methylation than non-carriers (p = 0.0259). Further studies are necessary in order to explain relations with the phenotype and DNA methylation due to the absence of functional evidence for rs780807 in CUBN.

Maternal genotypes of folate/one-carbon metabolism gene variants and nonsyndromic cleft lip with or without cleft palate risk in Chile.

The aim of this study was to evaluate, in a case-control design, the association between maternal genotypes for variants in 23 genes involved in folate/one-carbon metabolism and nonsyndromic cleft lip with or without cleft palate (NSCL/P) in a Chilean population. After applying several filters to an Illumina array, we extracted 175 single nucleotide polymorphisms (SNPs) from 150 mothers of NSCL/P cases and 150 control women. Association was evaluated using computed odds ratio (OR) with a 95% confidence interval (95% CI) in additive, recessive, and dominant models. After multiple comparison correction, only SNP rs4451422 (A>C), located 237 bp downstream of the gene encoding the human folylpolyglutamate synthetase (FPGS), maintained a significant association with NSCL/P in the offspring (OR 3.03; 95% CI 1.69-5.26). The variant rs4451422 is associated with a decrease in FPGS expression according to database annotation. Our results lead to a new hypothesis that a lower activity of FPGS enzyme reduces intracellular folate levels and increases the risk of an offspring having NSCL/P.

Genetic variants in S-adenosyl-methionine synthesis pathway and nonsyndromic cleft lip with or without cleft palate in Chile.

BACKGROUND: The S-adenosyl-methionine (SAM) availability is crucial for DNA methylation, an epigenetic mechanism involved in nonsyndromic cleft lip with or without cleft palate (NSCL/P) expression. The aim of this study was to assess the association between single-nucleotide polymorphisms (SNPs) of genes involved in SAM synthesis and NSCL/P in a Chilean population. METHODS: In 234 cases and 309 controls, 18 SNPs in AHCY, MTR, MTRR, and MAT2A were genotyped, and the association between them and the phenotype was evaluated based on additive (allele), dominant, recessive and haplotype models, by odds ratio (OR) computing. RESULTS: Three deep intronic SNPs of MTR showed a protective effect on NSCL/P expression: rs10925239 (OR 0.68; p = 0.0032; q = 0.0192), rs10925254 (OR 0.66; p = 0.0018; q = 0.0162), and rs3768142 (OR 0.66; p = 0.0015; q = 0.0162). Annotations in expression database demonstrate that the protective allele of the three SNPs is associated with a reduction of MTR expression summed to the prediction by bioinformatic tools of its potentiality to modify splicing sites. CONCLUSIONS: The protective effect against NSCL/P of these intronic MTR SNPs seems to be related to a decrease in MTR enzyme expression, modulating the SAM availability for proper substrate methylation. However, functional analyses are necessary to confirm our findings. IMPACT: SAM synthesis pathway genetic variants are factors associated to NSCL/P. This article adds new evidence for folate related genes in NSCL/P in Chile. Its impact is to contribute with potential new markers for genetic counseling.

Nonsyndromic orofacial clefts in Chile: LINE-1 methylation and MTHFR variants.

Aim: To evaluate the risk of nonsyndromic orofacial clefts (NSOFCs) associated with LINE-1 methylation, as a marker of global DNA methylation, and the effect of MTHFR functional variants on this variable. Patients & methods: LINE-1 methylation was evaluated by bisulfite modification coupled to DNA pyrosequencing in 95 NSOFC cases and 95 controls. In these subjects, MTHFR genotypes for variants c.C677T (rs1801133) and c.A1298C (rs1801131) were obtained. Results: Middle levels (second tertile) of LINE-1 methylation increase the risk of NSOFCs. In addition, LINE-1 methylation depends on c.A1298C genotypes in controls but not in cases. Conclusion: A nonlinear association between global DNA methylation and NSOFCs was detected in this Chilean population, which appears to be influenced by MTHFR functional variants.

A SHMT1 variant decreases the risk of nonsyndromic cleft lip with or without cleft palate in Chile.

OBJECTIVE: To assess the association between polymorphic variants from SHMT1 and MTHFS genes, involved in the cytoplasmic futile folate cycle, and the risk of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in the Chilean population. SUBJECTS AND METHODS: In a sample of 139 Chilean NSCL/P cases and 278 controls, we obtained the genotypes for nine variants of SHMT1 and MTHFS and the association between them and the phenotype was evaluated using odds ratios (OR) in additive (allele), dominant, and recessive models. RESULTS: After correction for multiple comparisons, only the variant rs1979277 (G > A; p.Leu474Phe) from SHMT1 showed a significant and protective effect for additive (OR 0.60; 95% CI 0.42-0.86; p = .0054, q = 0.0488) and dominant models (OR 0.48; 95% CI 0.29-0.75; p = .0009; q = 0.0081). Our bioinformatic prediction plus functional evidence from previous reports demonstrate that the A allele for this missense variant decreases the enzymatic activity. CONCLUSIONS: Owing to the rs1979277 A allele, which reduces the cytoplasmic SHMT activity and has a higher frequency in controls than in NSCL/P cases, we hypothesized that a low enzyme activity may increase the cytoplasmic concentration of folates and, therefore, explain the protective role against OFCs.

Presencia y relaciones anatomofuncionales del ligamento discomaleolar: una revisión de la literatura / Presence and anatomofunctional relations of the discomaleolar ligament: a literature review

El Ligamento Discomaleolar es una estructura que no se describe en los textos clásicos de anatomía a pesar de ser descrito por primera vez por Rees, Pinto y luego por diversos autores como una estructura ligamentosa de tejido fibroelástico que conecta el cuello y el proceso anterior del martillo a través de la fisura petrotimpánica hasta la parte medioposterosuperior de la cápsula de la articulación temporomandibular (ATM), el disco articular y el ligamento esfenomandibular. Diversos estudios han reportado las implicaciones clínicas del ligamento discomaleolar y la relación entre los trastornos temporomandibulares con los síntomas asociados al oído medio. El objetivo de este estudio fue realizar una revisión sobre estudios que describen el ligamento discomaleolar y determinar si se considera una estructura independiente anatómica y funcionalmente y su relación con el oído medio. Se realizó una búsqueda de literatura científica identificó artículos donde se identifican las estructuras anatómicas asociadas a la articulación témporomandibular y el oído medio, fueron seleccionados 24 artículos según los criterios de selección. Los resultados obtenidos en los estudios seleccionados en esta revisión sugieren la existencia de una lámina o fascículo fibroso que conecta el disco de la ATM con el maléolo del oído medio, lo que validaría la presencia y relación entre el ligamento discomaleolar y los trastornos del oído medio.

The Discomaleolar Ligament is a structure that is not described in the classic texts of anatomy despite being described for the first time by Rees, Pinto and later by various authors as a ligamentous structure of fibroelastic tissue that connects the neck and the anterior process of the malleus through the petrotympanic cleft to the mid-superior part of the capsule of the temporomandibular joint (TMJ), the articular disc and the sphenomandibular ligament. Several studies have reported the clinical implications of the discomaleolar ligament and the relationship between temporomandibular disorders and symptoms associated with the middle ear. The aim of this study was to conduct a review of studies that describe the discomaleolar ligament and determine if an anatomically and functionally independent structure and its relation to the middle ear is considered. A search was performed of scientific literature identified articles where the anatomical structures associated with the temporomandibular joint and the middle ear were identified, 24 articles were selected according to the selection criteria. The results obtained in the studies selected in this review suggest the existence of a lamina or fibrous fascicle that connects the TMJ disc with the malleolus of the middle ear, which would validate the presence and relationship between the discomaleolar ligament and middle ear disorders.

Review of the Tanaka ligament in the temporomandibular joint: analyzing its scientific validity / Revisión del ligamento de tanaka en la articulación temporomandibular: analizando su validez científica

SUMMARY: The temporomandibular joint (TMJ) is composed of bony structures, cartilage, capsule, articular disc, synovial membrane and ligaments. Some authors consider the "Tanaka ligament" described in the 1980s by Terry Tanaka as an intra-capsular ligament of the TMJ that unites medially the articular disc and mandibular fossa. The aim of the present study was to analyze the use of the term "Tanaka ligament" in the literature evaluating the scientific support of its existence. A literature review was carried out under the terms "Tanaka Ligament [AND] TMJ" and "Ligamento Tanaka [AND] ATM" (Spanish and Portuguese) in the search engines: MEDLINEPubmed, Science Direct, Google Scholar, LILACS-Bireme and SciELO. Scientific articles and theses were considered in English, Spanish and Portuguese. A total of 1,355 studies were found, summing up the results of all the search engines, of which 8 studies (5 articles and 3 theses) were selected after applying inclusion and exclusion criteria, selection by title, abstract and content. Most of these studies were discarded because they had contents related to the TMJ and/or ligaments wherein an author used the surname "Tanaka", that were not related to the Tanaka ligament. Among the 8 selected studies, 6 of them cite text books, 1 cites a video published by Terry Tanaka and 1 cites a thesis. Most of these textbooks cited also refer to videos by Terry Tanaka and his books. Moreover, most of the anatomical literature does not consider this ligament as an individualized structure. Although there are descriptions of Tanaka's ligament in textbooks, the scientific support of its existence is based only on videos and texts by Terry Tanaka. The dissemination of knowledge associated with this ligament must be cautious, as there is a need for further morphological and functional studies to confirm its existence.

RESUMEN: La articulación temporomandibular (TMJ) se compone de estructuras óseas, cartílago, cápsula, disco articular, membrana sinovial y ligamentos. Algunos autores consideran el "ligamento de Tanaka" descrito en los años 80 por Terry Tanaka como un ligamento intra-capsular de la ATM que une medialmente el disco articular y la fosa mandibular. El objetivo del presente estudio fue analizar el uso del término "ligamento de Tanaka" en la literatura evaluando el soporte científico de su existencia. Se realizó una revisión de la literatura bajo los términos "Tanaka Ligament [AND] TMJ" y "Ligamento Tanaka [AND] ATM" (Español y Portugués) en los buscadores: MEDLINE-Pubmed, Science Direct, Google Académico, LILACS-Bireme y SciELO. Se consideraron artículos científicos y tesis en inglés, español y portugués. Se obtuvieron un total de 1.355 estudios, sumando los resultados de todos los motores de búsqueda, de los cuales se seleccionaron 8 estudios (5 artículos y 3 tesis) después de aplicar los criterios de inclusión y exclusión y la selección por título, resumen y contenido. La mayoría de estos estudios fueron descartados porque tenían contenidos relacionados con la ATM y/o ligamentos cuyo autor tenía el apellido "Tanaka", que no estaba relacionado con el ligamento de Tanaka. Entre los 8 estudios seleccionados, 6 de ellos citan libros de texto, uno cita un video publicado por Terry Tanaka y otro cita una tesis. La mayoría de estos libros citados también se refieren a los videos de Terry Tanaka y sus libros. Además, la mayor parte de la literatura anatómica no considera este ligamento como una estructura individualizada. Aunque hay descripciones del ligamento de Tanaka en los libros de texto, el apoyo científico de su existencia se basa sólo en videos y textos de Terry Tanaka. La difusión del conocimiento asociado a este ligamento debe ser cautelosa, revelando la necesidad de más estudios morfológicos y funcionales para confirmar su existencia.

Influence of transmucosal height in abutments of single and multiple implant-supported prostheses: a non-linear three-dimensional finite element analysis.

The aim of this study was to analyze the influence of three different transmucosal heights of the abutments in single and multiple implant-supported prostheses through the finite element method. External hexagon implants, MicroUnit, and EsthetiCone abutments were scanned and placed in an edentulous maxillary model obtained from a tomography database. The simulations were divided into two groups: (1) one implant with 3.75 × 10 mm placed in the upper central incisor, simulating a single implant-supported fixed prosthesis with an EsthetiCone abutment; and (2) two implants with 3.75 × 10 mm placed in the upper lateral incisors with MicroUnit abutments, simulating a multiple implant-supported prosthesis. Subsequently, each group was subdivided into three models according to the transmucosal height (1, 2, and 3 mm). A static oblique load at an angle of 45 degrees to the long axis of the implant in palatal-buccal direction of 150 and 75 N was applied for multiple and single implant-supported prosthesis, respectively. The implants and abutments were assessed according to the equivalent Von Mises stress analyses while the bone and ceramics were analyzed through maximum and minimum principal stresses. The total deformation values increased in all models, while the transmucosal height was augmented. The transmucosal height of the abutments influences the stress values at the bone, ceramics, implants, and abutments of both the single and multiple implant-supported prostheses, with the transmucosal height of 1 mm showing the lowest stress values.

Transmigrated canines associated to odontomas / Caninos transmigrados asociados a odontomas

We present the case of a 13-year-old patient with bilateral transmigration of mandibular canine associated with multiple composite odontoma. Impacted canines are very uncommon, with a 0.1 % to 3.6 % prevalence of appearance. The presence in the mandible is less frequent. The odontoma development is often associated with the impacted canines. The etiology is unknown but is associated with traumatic, infectious, hereditary or genetic factors. This pathology is asymptomatic and associated with eruption disorders in temporal and permanent dentition.

Presentamos el caso de un paciente de 13 años de edad con trasmigración bilateral de canino mandibular asociado a múltiples odontomas compuestos. Los caninos impactados son muy poco frecuentes, con una prevalencia de aparición de 0,1 % a 3,6 %. La presencia en la mandíbula es menos frecuente. El desarrollo de odontomas se asocia a menudo con los caninos impactados. La etiología es desconocida pero está asociada con factores traumáticos, infecciosos, hereditarios o genéticos. Esta patología es asintomática y está asociada a trastornos de erupción en dentición temporal y permanente.

Evaluación de la fuerza masticatoria máxima funcional en adultos jóvenes chilenos / Evaluation of functional maximum bite force in Chilean young adults

La fuerza masticatoria máxima funcional (FMMF) se ha definido como la máxima fuerza generada entre los dientes maxilares y mandibulares. Así el objetivo de esta investigación fue de obtener datos reales sobre las FMMF a nivel molar, premolar, canino e incisivo en individuos adultos jóvenes. El estudio incluyó una muestra de 50 individuos entre 18 y 25 años de edad, totalmente dentados y con perfil esqueletal tipo I y clase I molar y canino. Se utilizó como instrumento un dispositivo de medición de fuerzas portátil, realizando las medidas en la región molar, premolar, canina e incisiva. A los individuos se les indicó morder el instrumento con la mayor fuerza posible, alternando las diferentes zonas a medir, aplicándose tres mediciones en cada diente y registrando el mayor valor en cada zona. La media de las fuerzas ejercidas del sexo masculino fue de 698, 516, 322 y 220 N, en las regiones molar, premolar, canina e incisiva, respectivamente. Por otro lado, en el sexo femenino se observaron valores medios de 466, 431, 232 y 174 N en las regiones molar, premolar, canina e incisiva, respectivamente. Se puede concluir que se observaron diferencias significativas de FMMF entre ambos sexos en las diferentes regiones, identificando los mayores valores en los individuos de sexo masculino en la región molar. Además, se identificaron diferencias significativas de la FMMF sólo en la región canina del sexo masculino al relacionarlas con el lado del arco.

The Functional maximum bite force (FMMF) is defined as the maximum force generated between the maxillary and mandibular teeth. Therefore, the aim of this research was to obtain real data about the FMMF at a molar, premolar, canine and incisive level in young adult individuals. The study included a sample of 50 individuals between 18 and 25 years old, fully toothed with a skeletal type I and Class I molar and canine profile. The measuring instrument used was a portable force measuring device, making measurements in the molar, premolar, canine and incisive regions. Individuals were instructed to bite the instrument with the greatest possible force, alternating different areas to measure, applying three measurements on each tooth and recording the highest value in each zone. The average of the forces exerted by males was 698, 516, 322 and 220 N, in the molar regions, premolar, canine and incisor, respectively. Furthermore, in females average values of 466, 431, 232 and 174 N were observed in the molar, premolar, canine and incisor regions respectively. It can be concluded that significant differences were observed in the FMMF between the sexes in different regions, identifying the highest values in male subjects in the molar region. In addition,significant differences were identified in the FMMF of males only in the canine region when related to the side of the arch.

Assessment of buccal bone thickness of aesthetic maxillary region: a cone-beam computed tomography study.

PURPOSE: The aim of this study was to analyze the anatomical dimensions of the buccal bone walls of the aesthetic maxillary region for immediate implant placement, based upon cone-beam computed tomography (CBCT) scans in a sample of adult patients. METHODS: Two calibrated examiners analyzed a sample of 50 CBCT scans, performing morphometric analyses of both incisors and canines on the left and right sides. Subsequently, in the sagittal view, a line was traced through the major axis of the selected tooth. Then, a second line (E) was traced from the buccal to the palatal wall at the level of the observed bone ridges. The heights of the buccal and palatal bone ridges were determined at the major axis of the tooth. The buccal bone thickness was measured across five lines. The first was at the level of line E. The second was at the most apical point of the tooth, and the other three lines were equidistant between the apical and the cervical lines, and parallel to them. Statistical analysis was performed with a significance level of P≤0.05 for the bone thickness means and standard deviations per tooth and patient for the five lines at varying depths. RESULTS: The means of the buccal wall thicknesses in the central incisors, lateral incisors and canines were 1.14±0.65 mm, 0.95±0.67 mm and 1.15±0.68 mm, respectively. Additionally, only on the left side were significant differences in some measurements of buccal bone thickness observed according to age and gender. However, age and gender did not show significant differences in heights between the palatal and buccal plates. In a few cases, the buccal wall had a greater height than the palatal wall. CONCLUSIONS: Less than 10% of sites showed more than a 2-mm thickness of the buccal bone wall, with the exception of the central incisor region, wherein 14.4% of cases were ≥2 mm.

Description of intraoral pressures on sub-palatal space in young adult patients with normal occlusion.

Under normal conditions, the oral cavity presents a perfect system of equilibrium between teeth, soft tissues and tongue. The equilibrium of soft tissues forms a closed capsular matrix, generating differences with the atmospheric environment. This difference is known as intraoral pressure. Negative intraoral pressure is fundamental to the stabilization of the soft palate and tongue, reducing neuromuscular activity for the permeability of the respiratory tract. Thus, the aim of this study was to describe the variations of intraoral pressure of the sub-palatal space (SPS) under different physiological conditions and biofunctional phases. A case series was conducted with 20 individuals aged between 18 and 25. The intraoral pressures were measured through a system of cannulae connected to a digital pressure meter in the SPS during seven biofunctional phases. Descriptive statistics were used based on the mean and standard deviation. The data recorded pressure variations under physiological conditions, reaching 65 mbar as the intraoral peak in forced inspiration. In the swallowing phase, peaks reached -91.9 mbar. No pressure variations were recorded in terms of atmospheric changes with the mouth open and semi-open. The data obtained during the swallowing and forced inspiration phases indicated forced lingual activity. In the swallowing phase, the adequate position of the tongue creates negative intraoral pressure, which represents a fundamental mechanism for the physical stabilization of the soft palate. This information could contribute to subsequent research into the treatment of primary roncopathies.

Caracterización morfométrica del reborde anterior de la maxila mediante tomografía computarizada cone-beam / Morphometric characterization of anterior maxillary alveolar ridge by cone-beam computed tomography

Las imágenes obtenidas por Tomografía Computarizada Cone-Beam (TCCB) permiten determinar las relaciones de estructuras anatómicas tridimensionalmente y superar limitaciones de la radiografía convencional. El objetivo de este estudio fue describir las características morfométricas de la zona anterior del maxilar y su relación con los dientes canino y premolares mediante exámenes de TCCB. Se realizó un estudio descriptivo sobre 50 imágenes de TCCB siguiendo una sistemática de observación tridimensional se ubicaron puntos anatómicos entre dientes y paredes del seno maxilar, y se trazaron tangentes para su medición. Se calculo la Media y DE para cada parámetro, y la normalidad de la distribución se comprobó mediante la prueba de Kolmogorov-Smirnov. Los datos fueron comparados con la prueba ANOVA, con una valor p < 0,05 como significativo. El análisis de la relación entre los dientes y la pared anterior del seno maxilar, mostró que en un 80% de los casos se relacionó con el canino y 20% con el primer premolar. La menor altura entre el reborde alveolar y la pared inferior del seno maxilar se observó a nivel del segundo premolar con 13,54±0,30 mm en el lado derecho y 14,65± 0,30 mm en el izquierdo. Se registraron diferencias significativas en relación a las mediciones morfométricas y la variable rango etáreo. Los datos obtenidos en este estudio complementan las características morfométricas de la zona anterior del maxilar, lo que permite ejecutar tratamientos de implantes bajo una base morfológica científica y minimizando al máximo los riesgos de fracaso o daño a las estructuras anatómicas relacionadas.

The images obtained by Cone -Beam Computed Tomography (CBCT) allow the determination of three-dimensional relationships of anatomical structures and overcome limitations of conventional radiography. The aim of this study was to describe the morphometric characteristics of the anterior maxilla and its relation to canine and premolars by CBCT exams. A descriptive study on 50 CBCT images was made, following a systematic observation of three-dimensional anatomical points between teeth and maxillary sinus walls, they were located and plotted tangent for measurement. The Mean and SD was calculated for each parameter, and the normality of distribution was tested by Kolmogorov -Smirnov test. Data were compared by ANOVA test, with a p value <0.05 as significant. The analysis of the relationship between the teeth and the anterior wall of the maxillary sinus, showed that in 80% of cases are associated with the canine and in 20% to first molar. The lower height between the alveolar ridge and the inferior wall of the maxillary sinus was observed at the second premolar with 13.54±0.30 mm on the right side and 14.65±0.30 mm on the left. Significant differences were recorded in relation to morphometric measurements and age range variable. The data obtained in this study complement the morphometric characteristics of the anterior maxilla, allowing implant treatments in a scientific morphological basis and minimizing the level of risk of failure or damage to the anatomical structures related.