Differential Effect of Positive End-Expiratory Pressure Strategies in Patients With ARDS: A Bayesian Analysis of Clinical Subphenotypes.

BACKGROUND: ARDS is a heterogeneous condition with two subphenotypes identified by different methodologies. Our group similarly identified two ARDS subphenotypes using nine routinely available clinical variables. However, whether these are associated with differential response to treatment has yet to be explored. RESEARCH QUESTION: Are there differential responses to positive end-expiratory pressure (PEEP) strategies on 28-day mortality according to subphenotypes in adult patients with ARDS? STUDY DESIGN AND METHODS: We evaluated data from two prior ARDS trials (Higher vs Lower Positive End-Expiratory Pressures in Patients With the ARDS [ALVEOLI] and the Alveolar Recruitment in ARDS Trial [ART]) that compared different PEEP strategies. We classified patients into one of two subphenotypes as described previously. We assessed the differential effect of PEEP with a Bayesian hierarchical logistic model for the primary outcome of 28-day mortality. RESULTS: We analyzed data from 1,559 patients with ARDS. Compared with lower PEEP, a higher PEEP strategy resulted in higher 28-day mortality in patients with subphenotype A disease in the ALVEOLI study (OR, 1.61; 95% credible interval [CrI], 0.90-2.94) and ART (OR, 1.73; 95% CrI, 1.01-2.98), with a probability of harm resulting from higher PEEP in this subphenotype of 94.3% and 97.7% in the ALVEOLI and ART studies, respectively. Higher PEEP was not associated with mortality in patients with subphenotype B disease in each trial (OR, 0.95 [95% CrI, 0.51-1.73] and 1.00 [95% CrI, 0.63-1.55], respectively), with probability of benefit of 56.4% and 50.7% in the ALVEOLI and ART studies, respectively. These effects were not modified by Pao2 to Fio2 ratio, driving pressure, or the severity of illness for the cohorts. INTERPRETATION: We found evidence of differential response to PEEP strategies across two ARDS subphenotypes, suggesting possible harm with a higher PEEP strategy in one subphenotype. These observations may assist with predictive enrichment in future clinical trials.

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.

HLA-DMB alleles and haplotypes in Ecuador (Cuenca) Amerindians: Importance for HLA and disease studies.

HLA-DMB allele frequencies and HLA-DBM-DRB1-DQB1 extended haplotypes were studied for the first time in Amerindians (Cuenca city area, Ecuador). It was found that most common extended haplotypes gathered the most frequent HLA-DRB1 Amerindian alleles. HLA-DMB polymorphism studies may be important to uncover HLA and diseases pathogenesis and also in an extended HLA haplotype frameshift. HLA-DM molecule has a crucial role together with CLIP protein in HLA class II peptide presentation. HLA extended haplotypes including complement and non classical genes alleles are proposed to HLA and disease studies.

Class II HLA in Georgia Caucasus Tbilisi Georgians and their Mediterranean ancestry: The Usko Mediterranean languages.

Georgia (or Sakartvelo in its own language) is a South Caucasus Mts. country with its easternmost part is enigmatically named Iberia, like the Iberian Peninsula, which may refer to rivers "Kura" and "Ebro" or their valleys respectively. Most of their inhabitants speak Georgian which is included within Dene-Caucasian group and Usko-Mediterranean subgroup of languages. The latter includes Basque, Berber, ancient Iberian-Tartessian, Etruscan, Hittite, Minoan Lineal A and others. In the present paper, HLA class II -DRB1 and -DQB1 alleles has been studied and extended haplotypes calculated. Most frequent haplotypes are also of Mediterranean origin (i. e.: (A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*51)-DRB1*13:01-DQB1*06:03, or (A*24-B*35)-DRB1*01:01-DQB1*05:01) and DA genetic distances show that closest world populations to Georgians are Mediterraneans. Georgians also show common extended haplotypes ((A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*13)-DRB1*07:01-DQB1*02:01 and (A*03-B*35)-DRB1*11:01-DQB1*03:01) with Svan people, a secluded population in North Georgia mountains. We can conclude that Georgians belong to a very old Mediterranean substratum according to both linguistics (Usko Mediterranean languages) and HLA genetics.

Root resorption in relation to a modified piezocision technique.

OBJECTIVES: To evaluate root resorption of lower incisors and canines quantitatively in a group of patients who underwent orthodontic treatment with piezocision and/or a collagen reinforcement technique with a fully resorbable three-dimensional (3D) collagen xenograft matrix compared with a control group. MATERIALS AND METHODS: The study sample of this secondary analysis consisted of 32 periodontally healthy patients with angle Class I malocclusion or mild Class II or III malocclusion and moderate irregularity index scores who underwent orthodontic treatment and had before (T0) and after treatment (T1) cone-beam computed tomography scans. Root resorption of lower incisors and canines was assessed quantitatively in the following four groups: the control group received orthodontic treatment without piezocision, experimental group 1 received orthodontic treatment with piezocision, experimental group 2 received orthodontic treatment with piezocision and a 3D collagen matrix, and experimental group 3 received orthodontic treatment with a 3D collagen matrix. RESULTS: An overall statistically significant decrease in root length from T0 to T1 for all groups was observed (P < .05). However, there was no significant difference among the groups in the amount of root length decrease from T0 to T1. CONCLUSIONS: Orthodontic treatment combined with piezocision does not increase the risk of root resorption of lower incisors and canines when compared with orthodontic treatment without acceleration techniques. More studies with larger samples should be undertaken to confirm these results.

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.

Gene Expression Scoring of Immune Activity Levels for Precision Use of Hydrocortisone in Vasodilatory Shock.

PURPOSE: Among patients with vasodilatory shock, gene expression scores may identify different immune states. We aimed to test whether such scores are robust in identifying patients' immune state and predicting response to hydrocortisone treatment in vasodilatory shock. MATERIALS AND METHODS: We selected genes to generate continuous scores to define previously established subclasses of sepsis. We used these scores to identify a patient's immune state. We evaluated the potential for these states to assess the differential effect of hydrocortisone in two randomized clinical trials of hydrocortisone versus placebo in vasodilatory shock. RESULTS: We initially identified genes associated with immune-adaptive, immune-innate, immune-coagulant functions. From these genes, 15 were most relevant to generate expression scores related to each of the functions. These scores were used to identify patients as immune-adaptive prevalent (IA-P) and immune-innate prevalent (IN-P). In IA-P patients, hydrocortisone therapy increased 28-day mortality in both trials (43.3% vs 14.7%, P = 0.028) and (57.1% vs 0.0%, P = 0.99). In IN-P patients, this effect was numerically reversed. CONCLUSIONS: Gene expression scores identified the immune state of vasodilatory shock patients, one of which (IA-P) identified those who may be harmed by hydrocortisone. Gene expression scores may help advance the field of personalized medicine.

Identification of acute respiratory distress syndrome subphenotypes de novo using routine clinical data: a retrospective analysis of ARDS clinical trials.

OBJECTIVES: The acute respiratory distress syndrome (ARDS) is a heterogeneous condition, and identification of subphenotypes may help in better risk stratification. Our study objective is to identify ARDS subphenotypes using new simpler methodology and readily available clinical variables. SETTING: This is a retrospective Cohort Study of ARDS trials. Data from the US ARDSNet trials and from the international ART trial. PARTICIPANTS: 3763 patients from ARDSNet data sets and 1010 patients from the ART data set. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was 60-day or 28-day mortality, depending on what was reported in the original trial. K-means cluster analysis was performed to identify subgroups. Sets of candidate variables were tested to assess their ability to produce different probabilities for mortality in each cluster. Clusters were compared with biomarker data, allowing identification of subphenotypes. RESULTS: Data from 4773 patients were analysed. Two subphenotypes (A and B) resulted in optimal separation in the final model, which included nine routinely collected clinical variables, namely heart rate, mean arterial pressure, respiratory rate, bilirubin, bicarbonate, creatinine, PaO2, arterial pH and FiO2. Participants in subphenotype B showed increased levels of proinflammatory markers, had consistently higher mortality, lower number of ventilator-free days at day 28 and longer duration of ventilation compared with patients in the subphenotype A. CONCLUSIONS: Routinely available clinical data can successfully identify two distinct subphenotypes in adult ARDS patients. This work may facilitate implementation of precision therapy in ARDS clinical trials.

Dental long axes using digital dental models compared to cone-beam computed tomography.

OBJECTIVE: Standard methods of evaluating tooth long axes are not comparable (digital dental models [DDMs], panoramic and cephalometric radiographs) or expose patients to more radiation (cone-beam computed tomography [CBCT]). This study aimed to compare angular changes in tooth long axes using DDMs vs using CBCTs. SETTINGS AND SAMPLE POPULATION: Secondary data analysis of DDMs and CBCTs, taken before and after orthodontic treatment with piezocision of 24 patients. METHODS: Angular changes in tooth long axes were evaluated using landmarks on first molars (centre of the occlusal surface and centre of the furcation), canines and incisors (cusp tip and centre of the root at the cementoenamel junction). Wilcoxon test, intraclass correlation coefficient (ICC) and Bland-Altman plots were used to test intra- and inter-rater agreement and compare DDM and CBCT measurements. RESULTS: The mesiodistal angulation and buccolingual inclination DDM measurements were reproducible. Overall mean differences between DDM and CBCT measurements of mesiodistal angulation, 1.9°±1.5°, and buccolingual inclination, 2.2 ± 2.2°, were not significant for all teeth. ICC between DDM and CBCT measurements ranged from good (0.85 molars) to excellent (0.94 canines; 0.96 incisors). The percentages of measurements outside the range of ±5 were 17.4% for molars, 13.8% for canines and 4.5% for incisors. CONCLUSIONS: DDM assessment of changes in tooth long axes has good reproducibility and yields comparable measurements to those obtained from CBCT within a 5° range. These findings lay the groundwork for machine learning approaches that synthesize crown and root canal information towards planning tooth movement without the need for ionizing radiation scans.

Automatic Segmentation of Dental Root Canal and Merging with Crown Shape.

In this paper, machine learning approaches are proposed to support dental researchers and clinicians to study the shape and position of dental crowns and roots, by implementing a Patient Specific Classification and Prediction tool that includes RootCanalSeg and DentalModelSeg algorithms and then merges the output of these tools for intraoral scanning and volumetric dental imaging. RootCanalSeg combines image processing and machine learning approaches to automatically segment the root canals of the lower and upper jaws from large datasets, providing clinical information on tooth long axis for orthodontics, endodontics, prosthodontic and restorative dentistry procedures. DentalModelSeg includes segmenting the teeth from the crown shape to provide clinical information on each individual tooth. The merging algorithm then allows users to integrate dental models for quantitative assessments. Precision in dentistry has been mainly driven by dental crown surface characteristics, but information on tooth root morphology and position is important for successful root canal preparation, pulp regeneration, planning of orthodontic movement, restorative and implant dentistry. In this paper we propose a patient specific classification and prediction of dental root canal and crown shape analysis workflow that employs image processing and machine learning methods to analyze crown surfaces, obtained by intraoral scanners, and three-dimensional volumetric images of the jaws and teeth root canals, obtained by cone beam computed tomography (CBCT).

Buccal bone defects and transversal tooth movement of mandibular lateral segments in patients after orthodontic treatment with and without piezocision: A case-control retrospective study.

INTRODUCTION: This study aimed to compare the extent of buccal bone defects (dehiscences and fenestrations) and transversal tooth movement of mandibular lateral segments in patients after orthodontic treatment with and without piezocision in cone-beam computed tomography and digital dental models. METHODS: The study sample of this study consisted of cone-beam computed tomography scans and digital dental models taken before (T0) and after (T1) orthodontic treatment of 36 patients with moderate mandibular anterior crowding. The experimental group consisted of 17 patients that had piezocision performed at the beginning of treatment with the goal of accelerating tooth movement, which was compared with 19 patients who did not receive piezocision. The measurement of bone defects, buccolingual inclination, and transversal distances of the tooth in the mandibular lateral segments (mandibular canines, premolars, and first molars) were evaluated at baseline and at the end of the orthodontic treatment. RESULTS: Overall, an increase in dehiscences, buccal inclination, and arch width from T0 to T1 was observed in both groups, but no statistically significant difference was found between groups. A significant increase in fenestrations from T0 to T1 was observed only for the canines in the experimental group. No statistically significant association was found between the increase of dehiscences and the amount of buccolingual inclination or transversal width changes. However, the changes in transversal width were statistically significantly associated with the increase in buccal inclination at the canines, first and second premolars. CONCLUSIONS: No significant differences were found in buccal dehiscences and transversal tooth movement (buccolingual inclination and arch width) of mandibular lateral segments between patients after orthodontic treatment with and without piezocision. Dehiscences, buccal inclination, and arch width significantly increased from T0 to T1 in both groups.

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.

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 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.

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.

Comparison of linear and angular changes assessed in digital dental models and cone-beam computed tomography.

OBJECTIVE: To compare the three-dimensional (3D) linear displacements and the mesiodistal and buccolingual angulation changes after orthodontic treatment in digital dental models (DDMs) and 3D models derived from cone-beam computed tomography (CBCT). SETTINGS AND SAMPLE POPULATION: Digital dental model and CBCT scans were selected from 24 adults who had undergone orthodontic treatment for mandibular anterior crowding. MATERIAL AND METHODS: 3D linear displacements and changes in angular measurements (mesiodistal and buccolingual angulation) were assessed in pre- and post-treatment DDM and CBCT images using the software ITK-snap and 3D SlicerCMF. Intra- and inter-rater agreement of measurements in DDM and CBCT were tested using the intraclass correlation coefficient (ICC). DDM and CBCT measurements were compared using the Wilcoxon test (P < .05), ICC and Bland-Altman plots. RESULTS: Intra- and inter-rater agreement varied from good (ICC > 0.75) to excellent (ICC > 0.90) for both DDM and CBCT measurements. Although no significant difference between DDM and CBCT methods was observed for linear measurements of tooth movement, the angular assessments were different for most measurements. The agreement between measurements from both assessments varied from poor to excellent. CONCLUSIONS: Longitudinal assessments of tooth movements including 3D linear displacements and mesiodistal and buccolingual angulation are reproducible when using both DDM and CBCT. Changes in angular measurements due to orthodontic treatment are discordant when measured in the digital models (clinical crown) and in the CBCT images (whole tooth).

Gorgan (Iran) population HLA genetics and anthropology.

Gorgan (Iran) have been studied for HLA-A, -B, -C, -DRB1 and -DQB1 genes for the first time. They are Turkmen and originated in East Asia around Altai Mts; they originally spoke a Turk language classified within the Turkish-Oguz group. Peripheral blood samples were collected from Gorgan City (Iran) and HLA typed by standard methodology. HLA allele frequencies were compared with 7984 chromosomes of other World populations and it was shown existence of admixture of Siberian and Mediterranean HLA characters in this population, probably due to longlasting contact with Persians. Three new HLA extended haplotypes were found: A*01:01-B*35:01-DRB1*03:01-DQB1*02:01, A*30:01-B*13:01-DRB1*15:01-DQB1*02:01 and A*31:01-B*35:01-DRB1*15:01-DQB1*03:01. Gorgan (Iran) were most close to Chuvashians (Noth Caspian Sea, Russia) and Siberians, like Tuvinians, Mansi and Buryats in Neighbour Joining and Vista analyses. It is established a relationship of this population with Kurgan (Gorgan, Iran) archaeological mounds culture. However, their kinship with Scythians (2nd century BC) and Sarmatians (4th century AD) is obscure although both of them spoke a Persian language.

Patient Specific Classification of Dental Root Canal and Crown Shape.

This paper proposes machine learning approaches to support dentistry researchers in the context of integrating imaging modalities to analyze the morphology of tooth crowns and roots. One of the challenges to jointly analyze crowns and roots with precision is that two different image modalities are needed. Precision in dentistry is mainly driven by dental crown surfaces characteristics, but information on tooth root shape and position is of great value for successful root canal preparation, pulp regeneration, planning of orthodontic movement, restorative and implant dentistry. An innovative approach is to use image processing and machine learning to combine crown surfaces, obtained by intraoral scanners, with three dimensional volumetric images of the jaws and teeth root canals, obtained by cone beam computed tomography. In this paper, we propose a patient specific classification of dental root canal and crown shape analysis workflow that is widely applicable.

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.