Automated artificial intelligence-based three-dimensional comparison of orthodontic treatment outcomes with and without piezocision surgery.

OBJECTIVE(S): This study aims to evaluate the influence of the piezocision surgery in the orthodontic biomechanics, as well as in the magnitude and direction of tooth movement in the mandibular arch using novel artificial intelligence (AI)-automated tools. MATERIALS AND METHODS: Nineteen patients, who had piezocision performed in the lower arch at the beginning of treatment with the goal of accelerating tooth movement, were compared to 19 patients who did not receive piezocision. Cone beam computed tomography (CBCT) and intraoral scans (IOS) were acquired before and after orthodontic treatment. AI-automated dental tools were used to segment and locate landmarks in dental crowns from IOS and root canals from CBCT scans to quantify 3D tooth movement. Differences in mesial-distal, buccolingual, intrusion and extrusion linear movements, as well as tooth long axis angulation and rotation were compared. RESULTS: The treatment time for the control and experimental groups were 13.2 ± 5.06 and 13 ± 5.52 months respectively (P = .176). Overall, anterior and posterior tooth movement presented similar 3D linear and angular changes in the groups. The piezocision group demonstrated greater (P = .01) mesial long axis angulation of lower right first premolar (4.4 ± 6°) compared with control group (0.02 ± 4.9°), while the mesial rotation was significantly smaller (P = .008) in the experimental group (0.5 ± 7.8°) than in the control (8.5 ± 9.8°) considering the same tooth. CONCLUSION: The open source-automated dental tools facilitated the clinicians' assessment of piezocision treatment outcomes. The piezocision surgery prior to the orthodontic treatment did not decrease the treatment time and did not influence in the orthodontic biomechanics, leading to similar tooth movements compared to conventional treatment.

Superoxide Dismutase-3 Downregulates Laminin α5 Expression in Tumor Endothelial Cells via the Inhibition of Nuclear Factor Kappa B Signaling.

The balance between laminin isoforms containing the α5 or the α4 chain in the endothelial basement membrane determines the site of leukocyte diapedesis under inflammatory conditions. Extracellular superoxide dismutase (SOD3) induces laminin α4 expression in tumor blood vessels, which is associated with enhanced intratumor T cell infiltration in primary human cancers. We show now that SOD3 overexpression in neoplastic and endothelial cells (ECs) reduces laminin α5 in tumor blood vessels. SOD3 represses the laminin α5 gene (LAMA5), but LAMA5 expression is not changed in SOD1-overexpressing cells. Transcriptomic analyses revealed SOD3 overexpression to change the transcription of 1682 genes in ECs, with the canonical and non-canonical NF-κB pathways as the major SOD3 targets. Indeed, SOD3 reduced the transcription of well-known NF-κB target genes as well as NF-κB-driven promoter activity in ECs stimulated with tumor necrosis factor (TNF)-α, an NF-κB signaling inducer. SOD3 inhibited the phosphorylation and degradation of IκBα (nuclear factor of the kappa light polypeptide gene enhancer in B-cells inhibitor alpha), an NF-κB inhibitor. Finally, TNF-α was found to be a transcriptional activator of LAMA5 but not of LAMA4; LAMA5 induction was prevented by SOD3. In conclusion, SOD3 is a major regulator of laminin balance in the basement membrane of tumor ECs, with potential implications for immune cell infiltration into tumors.

Extracellular Superoxide Dismutase, the Endothelial Basement Membrane, and the WNT Pathway: New Players in Vascular Normalization and Tumor Infiltration by T-Cells.

Tumor-infiltrating lymphocytes (TILs) are major players in the immune-mediated control of cancer and the response to immunotherapy. In primary cancers, however, TILs are commonly absent, suggesting T-cell entry into the tumor microenvironment (TME) to be selectively restricted. Blood and lymph vessels are the first barriers that circulating T-cells must cross to reach the tumor parenchyma. Certainly, the crossing of the endothelial cell (EC) basement membrane (EC-BM)-an extracellular matrix underlying EC-is a limiting step in T-cell diapedesis. This review highlights new data suggesting the antioxidant enzyme superoxide dismutase-3 (SOD3) to be a regulator of EC-BM composition in the tumor vasculature. In the EC, SOD3 induces vascular normalization and endows the EC-BM with the capacity for the extravasation of effector T-cells into the TME, which it achieves via the WNT signaling pathway. However, when activated in tumor cells, this same pathway is reported to exclude TILs. SOD3 also regulates TIL density in primary human colorectal cancers (CRC), thus affecting the relapse rate and patient survival.

SOD3 boosts T cell infiltration by normalizing the tumor endothelium and inducing laminin-α4.

The conversion of a non-T cell-inflamed into a T cell-inflamed tumor microenvironment (TME) is a key to sensitizing tumors to T-cell-based immunotherapies. Recent data show that the extracellular superoxide dismutase (SOD3) alters endothelial basement membrane (EC-BM) composition, providing permissive signals that enhance tumor infiltration by effector T cells. Abbreviations: AJ, adherens junction; EC, endothelial cell; EC-BM, endothelial basement membrane; HIF, hypoxia-inducible factor; ICAM-1, intercellular adhesion molecule-1; LAMA4, laminin-α4; SOD3, superoxide dismutase-3; TME, tumor microenvironment; VCAM-1, vascular cell adhesion molecule-1; VEGF, vascular-endothelial growth factor.

Relationship between the polymorphism in the interleukin 1-ß and the treatment time of patients subjected to a modified piezocision technique.

AIM: We aimed to evaluate the correlation between the polymorphism of the interleukin 1-Beta (IL1-ß, +3954 C>T) and tooth movement, in a group of Colombian patients undergoing surgically accelerated orthodontic tooth movement. METHODS: The study was nested to a controlled clinical trial. Blood samples were taken from 11 women and 29 healthy Colombian male volunteers between 18 and 40 years old, after 1 year of starting orthodontic treatment. The patients presented malocclusion class I, with grade II or III. To detect the genetic polymorphism of the nucleotide +3954 C to T in the IL-1ß gene, we used a real-time PCR assay. RESULTS: Eleven individuals presented the allele 2 (T) heterozygous with the allele 1 (T/C) and 19 individuals were homozygous for the allele 1 (C/C). When analyzing the presence of the SNP, no significant differences were found in any of the variables. The best treatment was reflected in Group 3 (selective upper and lower alveolar decortication and 3D collagen matrix) and Group 4 (only selective alveolar decortication in the upper arch, with 3D collagen matrix), with 27% and 35% more speed respectively than in the control group. CONCLUSIONS: Our analyses indicated that a reduction in the total treatment time can be mostly potentiated by using decortication and collagen matrices and not for the presence of the allele 2 in the IL-1ß. Nevertheless, it is important that further studies investigate if the polymorphism could be associated with the speed of tooth movement and analyze the baseline protein levels.

OBJETIVO: Evaluar la correlación entre el polimorfismo de la interleucina 1-Beta (IL1-ß, +3954 C> T) y el movimiento de los dientes, en un grupo de pacientes colombianos sometidos a un movimiento dental ortodóncico acelerado quirúrgicamente. MÉTODOS: Este fue un estudio secundario derivado de un ensayo clínico aleatorio controlado. Se tomaron muestras de sangre de 11 mujeres y 29 voluntarios varones colombianos sanos entre 18 y 40 años, después de 1 año de comenzar el tratamiento de ortodoncia. Los pacientes presentaron maloclusión clase I, con grado II o III. Para detectar el polimorfismo genético del nucleótido +3954 C a T en el gen IL-1ß, se usó un ensayo de PCR en tiempo real. RESULTADOS: 11 individuos presentaron el alelo 2 (T) heterocigoto con el alelo 1 (T / C) y 19 individuos fueron homocigotos para el alelo 1 (C / C). Al analizar la presencia del SNP, no se encontraron diferencias significativas en ninguna de las variables. El mejor tratamiento se reflejó en el Grupo 3 (decorticación alveolar superior e inferior selectiva y matriz de colágeno 3D) y el Grupo 4 (solo decorticación alveolar selectiva en el arco superior, con matriz de colágeno 3D), con un 27% y un 35% más de velocidad, respectivamente, que en el grupo de control. CONCLUSIONES: Los análisis indicaron que una reducción en el tiempo total de tratamiento puede potenciarse principalmente mediante el uso de decorticación y matrices de colágeno y no por la presencia del alelo 2 en la IL-1ß. Sin embargo, es importante que otros estudios investiguen si el polimorfismo podría estar asociado con la velocidad del movimiento de los dientes y analizar los niveles de proteína de referencia.

SOD3 induces a HIF-2α-dependent program in endothelial cells that provides a selective signal for tumor infiltration by T cells.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs), mainly CD8+ cytotoxic T lymphocytes (CTL), are linked to immune-mediated control of human cancers and response to immunotherapy. Tumors have nonetheless developed specific mechanisms that selectively restrict T cell entry into the tumor microenvironment. The extracellular superoxide dismutase (SOD3) is an anti-oxidant enzyme usually downregulated in tumors. We hypothesize that upregulation of SOD3 in the tumor microenvironment might be a mechanism to boost T cell infiltration by normalizing the tumor-associated endothelium. RESULTS: Here we show that SOD3 overexpression in endothelial cells increased in vitro transmigration of naïve and activated CD4+ and CD8+ T cells, but not of myeloid cells. Perivascular expression of SOD3 also specifically increased CD4+ and CD8+ effector T cell infiltration into tumors and improved the effectiveness of adoptively transferred tumor-specific CD8+ T cells. SOD3-induced enhanced transmigration in vitro and tumor infiltration in vivo were not associated to upregulation of T cell chemokines such as CXCL9 or CXCL10, nor to changes in the levels of endothelial adhesion receptors such as intercellular adhesion molecule-1 (ICAM-1) or vascular cell adhesion molecule-1 (VCAM-1). Instead, SOD3 enhanced T cell infiltration via HIF-2α-dependent induction of specific WNT ligands in endothelial cells; this led to WNT signaling pathway activation in the endothelium, FOXM1 stabilization, and transcriptional induction of laminin-α4 (LAMA4), an endothelial basement membrane component permissive for T cell infiltration. In patients with stage II colorectal cancer, SOD3 was associated with increased CD8+ TIL density and disease-free survival. SOD3 expression was also linked to a T cell-inflamed gene signature using the COAD cohort from The Cancer Genome Atlas program. CONCLUSION: Our findings suggest that SOD3-induced upregulation of LAMA4 in endothelial cells boosts selective tumor infiltration by T lymphocytes, thus transforming immunologically "cold" into "hot" tumors. High SOD3 levels are associated with human colon cancer infiltration by CD8+ T cells, with potential consequences for the clinical outcome of these patients. Our results also uncover a cell type-specific, distinct activity of the WNT pathway for the regulation of T cell infiltration into tumors.

Relationship between the polymorphism in the interleukin 1-β and the treatment time of patients subjected to a modified piezocision technique / Relación entre el polimorfismo en la interleucina 1-β y el tiempo de tratamiento de pacientes sometidos a una técnica de piezocisión modificada

Abstract Aim: We aimed to evaluate the correlation between the polymorphism of the interleukin 1-Beta (IL1-β, +3954 C>T) and tooth movement, in a group of Colombian patients undergoing surgically accelerated orthodontic tooth movement. Methods: The study was nested to a controlled clinical trial. Blood samples were taken from 11 women and 29 healthy Colombian male volunteers between 18 and 40 years old, after 1 year of starting orthodontic treatment. The patients presented malocclusion class I, with grade II or III. To detect the genetic polymorphism of the nucleotide +3954 C to T in the IL-1β gene, we used a real-time PCR assay. Results: Eleven individuals presented the allele 2 (T) heterozygous with the allele 1 (T/C) and 19 individuals were homozygous for the allele 1 (C/C). When analyzing the presence of the SNP, no significant differences were found in any of the variables. The best treatment was reflected in Group 3 (selective upper and lower alveolar decortication and 3D collagen matrix) and Group 4 (only selective alveolar decortication in the upper arch, with 3D collagen matrix), with 27% and 35% more speed respectively than in the control group. Conclusions: Our analyses indicated that a reduction in the total treatment time can be mostly potentiated by using decortication and collagen matrices and not for the presence of the allele 2 in the IL-1β. Nevertheless, it is important that further studies investigate if the polymorphism could be associated with the speed of tooth movement and analyze the baseline protein levels.

Resumen Objetivo: Evaluar la correlación entre el polimorfismo de la interleucina 1-Beta (IL1-β, +3954 C> T) y el movimiento de los dientes, en un grupo de pacientes colombianos sometidos a un movimiento dental ortodóncico acelerado quirúrgicamente. Métodos: Este fue un estudio secundario derivado de un ensayo clínico aleatorio controlado. Se tomaron muestras de sangre de 11 mujeres y 29 voluntarios varones colombianos sanos entre 18 y 40 años, después de 1 año de comenzar el tratamiento de ortodoncia. Los pacientes presentaron maloclusión clase I, con grado II o III. Para detectar el polimorfismo genético del nucleótido +3954 C a T en el gen IL-1β, se usó un ensayo de PCR en tiempo real. Resultados: 11 individuos presentaron el alelo 2 (T) heterocigoto con el alelo 1 (T / C) y 19 individuos fueron homocigotos para el alelo 1 (C / C). Al analizar la presencia del SNP, no se encontraron diferencias significativas en ninguna de las variables. El mejor tratamiento se reflejó en el Grupo 3 (decorticación alveolar superior e inferior selectiva y matriz de colágeno 3D) y el Grupo 4 (solo decorticación alveolar selectiva en el arco superior, con matriz de colágeno 3D), con un 27% y un 35% más de velocidad, respectivamente, que en el grupo de control. Conclusiones: Los análisis indicaron que una reducción en el tiempo total de tratamiento puede potenciarse principalmente mediante el uso de decorticación y matrices de colágeno y no por la presencia del alelo 2 en la IL-1β. Sin embargo, es importante que otros estudios investiguen si el polimorfismo podría estar asociado con la velocidad del movimiento de los dientes y analizar los niveles de proteína de referencia.

Interleukin 1-beta (IL-1ß) polymorphism and orthodontics: a systematic review / Polimorfismo de la interleuquina 1 beta (IL-1ß) y ortodoncia: revisión sistemática

ABSTRACT Introduction: the aim of this systematic review is to explore the published literature to analyze the relationship between polymorphism of interleukin 1-beta (IL-1β) and orthodontics. Methods: the search strategy developed for Medline, Scopus and Embase was used, verifying search records and selecting articles according to the guidelines set forth by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two researchers evaluated studies in humans undergoing orthodontic treatment that evaluate IL-1β polymorphism, movement speed and/or root resorption, including clinical trials, case-control studies, cross-sectional studies, and cohort studies, published up to April 2017. Results: of the 123 relevant articles identified, 9 studies published between 2001 and 2016 were included in the detailed analysis. Studies on tooth movement generally agree that there is an increase in IL-1β levels in the first hours after starting the orthodontic treatment. Conclusion: an association of IL-1β polymorphism with external root resorption and tooth movement speed was found.

RESUMEN Introducción: el objetivo de esta revisión sistemática es analizar, a través de la literatura publicada, la relación entre el polimorfismo de la interleuquina 1 beta (IL-1β) y la ortodoncia. Métodos: se aplicó la estrategia de búsqueda desarrollada para Medline, Scopus y Embase y se verificaron los registros de la búsqueda y los artículos seleccionados de acuerdo a los lineamientos de la declaración para Revisiones Sistemáticas y Metaanálisis (PRISMA). Dos investigadores evaluaron los estudios en humanos sometidos a tratamiento de ortodoncia, donde se evalúan el polimorfismo de la IL-1β y la velocidad de movimiento y/o resorción radicular, como ensayos clínicos, estudios de casos y controles, estudios transversales o estudios de cohortes, publicados hasta abril de 2017. Resultados: de los 123 estudios relevantes identificados, 9 de ellos, publicados entre 2001 y 2016, fueron incluidos en el análisis detallado. Los estudios de movimiento dental concuerdan en el aumento de los niveles de IL-1β en las primeras horas de inicio del tratamiento ortodóncico. Conclusión: se encontró asociación del polimorfismo de la IL-1β con la resorción radicular externa y la velocidad de movimiento dental.

Accuracy and reliability of mandibular digital model registration with use of the mucogingival junction as the reference.

OBJECTIVE: The aim of the study was to validate a method of mandibular digital model (DM) registration, acquired from an intraoral scanner, compared with high-resolution voxel-based cone beam computed tomography (CBCT) registration with use of the mucogingival junction as the reference. STUDY DESIGN: Pre- and post-treatment CBCT and DM images from 12 adults were randomly selected from an initial sample of 40 patients who had undergone orthodontic treatment. The DM registration was performed in 6 steps: (1) construction of 3-dimensional (3-D) volumetric label maps of CBCT scans, (2) voxel-based registration of CBCT scans, (3) prelabeling of CBCT images, (4) approximation and registration of DM models to the corresponding CBCT models, (5) mucogingival-junction registration of pretreatment and post-treatment DM images, and (6) measurements. The Mann-Whitney U test was used to calculate the significance of differences between the CBCT and DM registrations. The intraclass correlation coefficient (ICC) was performed to assess reproducibility of the registration method. RESULTS: When registered CBCT models and registered DM models were compared, no statistically significant differences in the measurements were found (right-left P = .267; anterior-posterior P = .238; superior-inferior P = .384; and 3-D P = .076). ICC showed excellent intra- and inter-rater correlation (ICC > 0.90). CONCLUSIONS: The method of DM registration of the mandible with use of the mucogingival junction as the reference is accurate, reliable, and reproducible.

SOD3 improves the tumor response to chemotherapy by stabilizing endothelial HIF-2α.

One drawback of chemotherapy is poor drug delivery to tumor cells, due in part to hyperpermeability of the tumor vasculature. Extracellular superoxide dismutase (SOD3) is an antioxidant enzyme usually repressed in the tumor milieu. Here we show that specific SOD3 re-expression in tumor-associated endothelial cells (ECs) increases doxorubicin (Doxo) delivery into and chemotherapeutic effect on tumors. Enhanced SOD3 activity fostered perivascular nitric oxide accumulation and reduced vessel leakage by inducing vascular endothelial cadherin (VEC) transcription. SOD3 reduced HIF prolyl hydroxylase domain protein activity, which increased hypoxia-inducible factor-2α (HIF-2α) stability and enhanced its binding to a specific VEC promoter region. EC-specific HIF-2α ablation prevented both the SOD3-mediated increase in VEC transcription and the enhanced Doxo effect. SOD3, VEC, and HIF-2α levels correlated positively in primary colorectal cancers, which suggests a similar interconnection of these proteins in human malignancy.

Orthodontic treatment in patient with idiopathic root resorption: A case report

Multiple idiopathic external root resorption is a rare pathological condition usually detected as an incidental radiographic finding. External root resorption of permanent teeth is a multifactorial process related to several local and systemic factors. If an etiological factor cannot be identified for root resorption, the term "idiopathic" is applied. This report presents a case of multiple idiopathic apical root resorption. The condition was found in a young female patient seeking orthodontic treatment due to malocclusion. This kind of resorption starts apically and progresses coronally, causing a gradual shortening and rounding of the remaining root. Patients with this condition are not the ideal candidates for orthodontic treatment; however, the aim of this report is to describe an unusual case of idiopathic root resorption involving the entire dentition, and to present the orthodontic treatment of this patient. It describes the progress and completion of orthodontic therapy with satisfactory end results.

A reabsorção radicular externa idiopática é uma rara condição patológica, normalmente detectada como um achado fortuito radiológico. Trata-se de um processo multifatorial, relacionado a diversos fatores locais e sistêmicos. Se um fator etiológico não for identificado, a reabsorção radicular é classificada como idiopática. Apresentamos o caso de uma paciente do sexo feminino com reabsorção radicular idiopática, que procurou tratamento ortodôntico para corrigir uma má oclusão. Esse tipo de reabsorção começa apicalmente e evolui coronalmente, provocando o encurtamento gradual e o arredondamento da raiz remanescente. Os pacientes com essa condição não são os candidatos ideais para o tratamento ortodôntico, no entanto, o objetivo desse relato é descrever um caso incomum de reabsorção radicular idiopática que envolveu toda a dentição. Além disso, pretende-se apresentar o tratamento ortodôntico da paciente. Também são descritos o progresso e a conclusão do tratamento ortodôntico, assim como os satisfatórios resultados finais.

Distalización con el C-DFD modificado con mini-tornillos. Reporte de caso / Distalization with a C-DFD modified with mini-screws. A case report

En la actualidad existen muchos dispositivos para distalizar los molares cuando se presenta una maloclusión clase II; como son la tracción extraoral, el péndulo dento y óseosoprtado, el distal jet, sliding jig entre otros. Todos con efectos secundarios indeseables. Este reporte de caso pretende ilustrar los resultados obtenidos con un dispositivo con anclaje cortical y óseo en una maloclusión clase II. Reporte de caso clínico en un paciente clase II esquelético y dental. Se usó un aparato de anclaje cortical, diseñado en la Universidad CES de Medellín, llamado Cortical Dual Forcé Distalizer (C-DFD), el cual fue modificado con un par de mini-tornillos para reforzar el anclaje, logrando la distalización superior de los molares evitando un tratamiento con exodoncias. El C-DFD es un distalizador óseo-soportado que logra un movimiento distal del primer molar superior.

There are currently many devices used for molar distalization when there is a Class II malocclusion; some of these devices include headgear, tooth-supported and bone-supported pendulums, the distal jet, and the sliding jig, among others. All of them have undesirable side effects. This case report aims to illustrate the results obtained by using a device with cortical and bone anchorage to treat a Class II malocclusion of a patient with a skeletal and dental class II malocclusion. A Cortical Dual Forcé Distalizer (C-DFD, a cortical-anchoring appliance designed at CES University in Medellín, Colombia was used. This device was modified by using a couple of mini-screws to reinforce anchorage, thus achieving upper distalization of molars and avoiding treatment with extractions. The C-DFD is a bone-supported distalizer that achieves a more controlled and in-body distal movement of the first upper molar, avoiding the inclinations produced by other distalizers.

Método de superposición estructural de Björk para evaluar crecimiento y desarrollo craneofacial / Björk structural superimposition method to evaluate craniofacial growth and development

La superposición cefalométrica es una herramienta indispensable en la práctica de la Ortodoncia ya que permite evaluar los cambios que sufre el complejo craneofacial a través del proceso de crecimiento y desarrollo o aquellos cambios logrados mediante un tratamiento. En la literatura se han descrito múltiples técnicas de superposición cefalométrica; la mayoría de ellas utilizan como puntos de referencia zonas anatómicas poco estables durante el periodo de crecimiento y desarrollo. El doctor Björk describió una técnica de superposición cefalométrica basada en estudios con implantes metálicos, lo cual permitió identificar puntos de referencia y zonas anatómicas mas estables durante este periodo, por lo que permite medir y valorar los cambios craneofaciales de una manera mas confiable. El Objetivo de este articulo es describir la técnica de superposición estructural de Björk para su utilización como herramienta en la practica clínica e investigativa de la Ortodoncia.

Cephalometric superimposition is a critical tool in Orthodontics when evaluating changes affecting the craniofacial complex through the process of growth and development, or those obtained with treatment. Several cephalometric superimposition techniques have been reported previously, but most of them use unstable anatomical landmarks as reference areas or points to establish changes during growth and development. Björk's method describes a cephalometric superimposition technique based on studies with metal implants which allowed to identify stable reference points during the growth and therefore enable the possibility of measuring and evaluating craniofacial changes in amore reliable manner. The objective of this article is to describe Björk structural superimposition method as a tool in clinical practice and research in Orthodontics.

Tratamiento de ortodoncia en paciente con síndrome de down / Orthodontic treatment of A patient with down's syndrome

El tratamiento de ortodoncia en pacientes con síndrome de Down ha sido un tema debatido durante muchos años por las deficiencias físicas y mentales de los pacientes y la dificultad en la cooperación con el tratamiento. El objetivo es lograr un buen vínculo odontólogo-paciente-acudiente para mejorar la calidad de vida de éstos, corrigiendo desde su respiración, su función masticatoria y llegando a una armonía estética facial. Este artículo muestra el resultado del tratamiento de ortodoncia de un paciente con síndrome de Down, con maloclusión clase III, mordida cruzada anterior y posterior, mordida abierta, deficiencia de tercio medio, perfil cóncavo, protrusión lingual e incompetencia labial. La aparatología fija con extracción asimétrica en el arco inferior y elásticos intermaxilares de clase III, fué el tratamiento elegido para corregir el overbite, overjet y lograr una muy buena intercuspidación y una estética facial y placas essix con elásticos de clase III se emplearon para la retención.

Orthodontic treatment in patients with Down Syndrome has been debated due to their physical and mental disabilities as well as the difficulty in cooperation during treatment. The purpose of treatment is to achieve a good dentist-patient- care provider relationship that improves the quality of life of the patient by correcting breathing, masticatory function and facial aesthetic harmony. This article presents the result of the orthodontic treatment of a patient with Down's Syndrome, with class III malocclusion, posterior and anterior crossbite, open bite, middle third deficiency, concave profile, tongue protrusion and lip incompetence. Fixed appliances with extractions in the lower arch and intermaxillary elastics for class III, are used in order to correct the overbite, overjet and achieve adequate intercuspation and facial aesthetics; essix plates and with class III elastic are used for retention.

HLA-G(∗)01:05N null allele in Mayans (Guatemala) and Uros (Titikaka Lake, Peru): evolution and population genetics.

HLA-G molecules seem to have a protective effect for the semi-allogeneic fetus by mother immunosuppression. Also, pregnancy pathologies have been associated to HLA-G(∗)01:05N "null allele". In addition, other general regulatory immune functions have been associated to HLA-G in infections, tumors and autoimmunity. Thus, it is striking that HLA(∗)01:05N allele is maintained in a substantial frequency in certain human populations. In the present work, we have analysed HLA-G allele frequencies in Amerindian Mayans from Guatemala and in Uros from Titikaka Lake "totora" (reed) floating islands (Peru). No HLA-G(∗)01:05N has been found in both of these Amerindian populations. Further studies in Worldwide populations show that the highest HLA-G(∗)01:05 allele frequencies are found in Middle East; these findings have a bearing in future clinical/epidemiological studies in Amerindians. This would suggest that either this area was close to the "null" allele origin (as predicted by us) and/or some evolutive pressures are maintaining these high frequencies in Middle East. However, the fact that Cercopithecinae primate family (primates postulated as distant human ancestors) has also a MHC-G "null" allele in all individuals suggests that this allele may confer some advantage either at maternal/fetal interface or at other immune HLA-G function level (tumors, infections, autoimmunity). Human HLA-G(∗)01:05N may produce HLA-G isoforms, like Cercopithecinae monkeys may, which may suffice for function.

Extraccion del primer molar permanente como una alternativa en el tratamiento de ortodoncia / Extractions of first permanent molars as a choice of the orthodontic treatment

La extracción de primeros molares permanentes es una alternativa de tratamiento en algunos casosde ortodoncia como aquellos que presentan apiñamiento moderado, biprotrusión, mordidas abiertas,clase II y III en casos en los cuales es necesario realizar exodoncias y en donde los primeros molaresestán en mal estado por caries extensas u otras alteraciones en su formación, lo que los hace maselegibles para ser extraidos evitando restauraciones extensas futuras o la necesidad de colocar implantespara remplazarlos . Este articulo describe tres casos con diferentes tipos de maloclusiones en los cualeslos primeros molares superiores y/o inferiores fueron elegidos para ser extraídos y así poder obtenerresultados clínicos óptimos tanto faciales como oclusales.

Extraction of First permanent molars is a treatment alternative in patients with moderate crowding, bimaxillaryprotrusion, open bites, class III, Class II, in cases of extensive caries or other developmental problems or to prevent the placement of implants to replace them. This article describes three different clinical cases in which first, upper and lower permanent molars were chosen to be extracted in order toobtain clinical, facial and oclusal good results.

Single-walled carbon nanotubes deliver peptide antigen into dendritic cells and enhance IgG responses to tumor-associated antigens.

We studied the feasibility of using single-wall carbon nanotubes (SWNTs) as antigen carriers to improve immune responses to peptides that are weak immunogens, a characteristic typical of human tumor antigens. Binding and presentation of peptide antigens by the MHC molecules of antigen presenting cells (APCs) is essential to mounting an effective immune response. The Wilm's tumor protein (WT1) is upregulated in many human leukemias and cancers and several vaccines directed at this protein are in human clinical trials. WT1 peptide 427 induces human CD4 T cell responses in the context of multiple human HLA-DR.B1 molecules, but the peptide has a poor binding affinity to BALB/c mouse MHC class II molecules. We used novel, spectrally quantifiable chemical approaches to covalently append large numbers of peptide ligands (0.4 mmol/g) onto solubilized SWNT scaffolds. Peptide-SWNT constructs were rapidly internalized into professional APCs (dendritic cells and macrophages) within minutes in vitro, in a dose dependent manner. Immunization of BALB/c mice with the SWNT-peptide constructs mixed with immunological adjuvant induced specific IgG responses against the peptide, while the peptide alone or peptide mixed with the adjuvant did not induce such a response. The conjugation of the peptide to SWNT did not enhance the peptide-specific CD4 T cell response in human and mouse cells, in vitro. The solubilized SWNTs alone were nontoxic in vitro, and we did not detect antibody responses to SWNT in vivo. These results demonstrated that SWNTs are able to serve as antigen carriers for delivery into APCs to induce humoral immune responses against weak tumor antigens.

Distracción osteogénica alveolar, una alternativa para el manejo de recidivas quirúrgicas de las maloclusiones esqueléticas clase II: reporte de un caso / Alveolar bone distraction an alternative for the correction of surgical relapse ofskeletal class II malocclusions: a case report

La distracción osteogénica es un proceso biológico de neo formación ósea a partir de dos segmentososeos previamente osteotomizados que se separan en forma gradual debido a una tracción mecánica incremental generada por un tornillo distractor. El proceso biológico da inicio cuando lasfuerzas de distracción posteriores a un periodo de latencia, se aplican sobre la matriz colágena que forma el callo óseo entre los segmentos de hueso seccionados,estimulando de esta forma la neoformacion ósea paralela al vector de distracción. Esta alternativa quirúrgica ha sido por décadasempleada para el alargamiento de extremidades, especialmente de huesos largos. Actualmente es utilizada con múltiples propósitos en el complejo maxilofacial, ofreciendo la posibilidad de modular la cantidad de hueso y demás tejidos blandos de los maxilares y de esta manera restableciendo suarquitectura en cualquier plano del espacio obteniendo muy buenos resultados. Este reporte de casopresenta la distracción osteogénica alveolar (DOA) como alternativa para el tratamiento de recidivas,secundarias a la corrección quirúrgica de discrepancias Maxilomandibulares clase II mediante la técnica osteotomía sagital de rama mandibular (OSRM) de avance; en pacientes donde no esposible una segunda intervención quirúrgica.

Osteogenic distraction is a biological process of osseous neoformation from two segments previouslysubjected to osteotomy which are separated in a gradual form by an incremental mechanical tractiongenerated by a distracting screw. The biological process begins when posterior distraction forcesare applied after a latency period on a collagenous matrix which forms a bony callous between thesectioned bone fragments stimulating in this form bone neoformation parallel to the distraction vector.This surgical alternative has been used for decades in the lengthening of limbs, especially in long bones. Currently it is used for multiple purposes in the craniofacial complex offering the possibility of modeling the amount of bone and surrounding soft tissues and in this way reestablishing its architecture in any spatial plane and obtaining very good results. A case report is presented of an alveolar bone distraction as an alternative for the treatment of relapse secondary to surgical correctionof Class II maxillofacial discrepancies with advanced sagittal osteotomy of the mandibular ramus in patients in which a second surgical intervention is not possible.

Distalización de molares maxilares con aparatos intraorales de nueva generación que no necesitan colaboración del paciente / Maxillary molar distalization with new generation intraoral appliances that does not require patient cooperation

Las alternativas de tratamiento de las maloclusiones de clase II esqueléticas y dentales incluyen las extracciones de dientes permanentes y la distalización de los molares maxilares con aparatos extraorales e intraorales. Estos últimos, no necesitan la cooperación del paciente, además, en ellos se han hecho variaciones importantes en su mecánica y diseño a lo largo de los años. Con el uso de los minitornillos se ha podido eliminar, en gran parte, los efectos de reacción como la vestibularización de los incisivos y la mesialización de los premolares. Este artículo sintetiza una revisión de la literatura de los últimos 20 años de los diferentes diseños y sistemas mecánicos que se han usado con éxito en la distalización de los molares maxilares.

The alternatives of treatment of class II skeletal and dental maloclussions included the extractions of permanent teeth and the maxillary molars distalization by extraoral devices and intraoral devices. The above mentioned, does not need cooperation of the patient. In addition, important variations have been mechanics and design throughout the years. With the miniscrews one could have eliminated, largely, the effects of reaction as the vestibularization of the incisor teeth and the mesialization of the bicuspid. This article is a synthesis of a review of the literature of last 20 years of the different designs and mechanical systems that have been used successfully in the distalization of the maxillary molars.

Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association.

The HLA-G gene displays several peculiarities that are distinct from those of classical HLA class I genes. The unique structure of the HLA-G molecule permits a restricted peptide presentation and allows the modulation of the cells of the immune system. Although polymorphic sites may potentially influence all biological functions of HLA-G, those present at the promoter and 3' untranslated regions have been particularly studied in experimental and pathological conditions. The relatively low polymorphism observed in the MHC-G coding region both in humans and apes may represent a strong selective pressure for invariance, whereas, in regulatory regions several lines of evidence support the role of balancing selection. Since HLA-G has immunomodulatory properties, the understanding of gene regulation and the role of polymorphic sites on gene function may permit an individualized approach for the future use of HLA-G for therapeutic purposes.