Live-cell chromosome dynamics and outcome of X chromosome pairing events during ES cell differentiation.

Random X inactivation represents a paradigm for monoallelic gene regulation during early ES cell differentiation. In mice, the choice of X chromosome to inactivate in XX cells is ensured by monoallelic regulation of Xist RNA via its antisense transcription unit Tsix/Xite. Homologous pairing events have been proposed to underlie asymmetric Tsix expression, but direct evidence has been lacking owing to their dynamic and transient nature. Here we investigate the live-cell dynamics and outcome of Tsix pairing in differentiating mouse ES cells. We find an overall increase in genome dynamics including the Xics during early differentiation. During pairing, however, Xic loci show markedly reduced movements. Upon separation, Tsix expression becomes transiently monoallelic, providing a window of opportunity for monoallelic Xist upregulation. Our findings reveal the spatiotemporal choreography of the X chromosomes during early differentiation and indicate a direct role for pairing in facilitating symmetry-breaking and monoallelic regulation of Xist during random X inactivation.

Diversity of Native Arbuscular Mycorrhiza Extraradical Mycelium Influences Antioxidant Enzyme Activity in Wheat Grown Under Mn Toxicity.

Sustainable agricultural practices based on the development of native arbuscular mycorrhizal fungi (AMF) can improve crop growth and stress tolerance in acidic soils with manganese toxicity. The beneficial effects are stronger when crops are colonized early in development by an intact extraradical mycelium (ERM), but are dependent on AMF assemblage. In wheat colonized by AMF associated to Lolium rigidum L. (LOL) or Ornithopus compressus (ORN), growth and stress tolerance are differently influenced. In the present study, this functional diversity was studied by evaluating the activity of ascorbate peroxidase (APX), catalase (CAT), glutathione reductase (GR), guaiacol peroxidase (GPX), superoxide dismutase (SOD) and Mn-SOD. ORN treatment promoted higher wheat shoot and root dry weights, a higher root protein content, decreased root APX, GR and SOD activities but a higher proportion of MnSOD activity. ORN associated microbiota differently manage antioxidant enzyme activity of succeeding wheat to improve growth.

Toxic levels of manganese in an acidic Cambisol alters antioxidant enzymes activity, element uptake and subcellular distribution in Triticum aestivum.

In the Montado system, in Portuguese Alentejo region, some Eutric Cambisols are known to promote manganese (Mn) toxicity in wheat. Variation on bioavailable Mn concentration depends on soil acidity, which can be increased by natural events (e.g. waterlogging) or human activity (e.g. excess use of chemical fertilizers). The effect of increasing soil Mn on crop element uptake, element distribution and oxidative stress was evaluated on winter wheat (Triticum aestivum). Plants were grown for 3 weeks in an acidic Cambisol spiked with increasing Mn concentrations (0, 45.2 and 90.4 mg MnCl2/Kg soil). Calcium (Ca), phosphorus (P), magnesium (Mg) and Mn were quantified in the soil solution, root and shoot tissues and respective subcellular fractions. The activity of the antioxidant enzymes ascorbate peroxidase (APX), catalase (CAT), glutathione reductase (GR), guaiacol peroxidase (GPX) and superoxide dismutase (SOD) were determined in extracts of wheat shoots and roots. Overall, increase in soil bioavailable Mn inhibited the uptake of other elements, increased the Ca proportion in the root apoplast, promoted the translocation of Mn and P to shoot tissues and increased their proportion in the shoot vacuoles. Wheat roots showed greater antioxidant enzymes activities than shoots. These activities decreased at the highest soil Mn concentration in both plant parts. Wheat roots appear to be more sensitive to oxidative stress derived from excess soil Mn and promote Mn translocation and storage in shoot vacuoles, probably in Mn and P complexes, as a detoxification strategy. Improvement in wheat production, in acidic soils, may rely on the enhancement of its Mn detoxification strategies.

Haemophagocytic Lymphohistiocytosis Associated With Anaplastic Large-Cell Lymphoma in a Young Woman.

Haemophagocytic lymphohistiocytosis is a syndrome of excessive immunological activation that can be triggered by various diseases, including haematological cancers. We report a case of a 25-year-old woman presenting with constitutional symptoms and a painful thoracic mass of four months duration. Laboratory exams showed pancytopenia, hypertriglyceridemia and extremely high serum ferritin levels. A whole-body computed tomography (CT) scan revealed splenomegaly and highlighted the mass on the deep tissues of the left breast; the biopsy was compatible with anaplastic large-cell lymphoma. Additionally, a bone marrow biopsy revealed haemophagocytosis, fulfilling the criteria for associated haemophagocytic lymphohistiocytosis. The patient was quickly sent for chemotherapy followed by autologous haematopoietic cell transplantation. She achieved a complete metabolic response and has been in clinical remission after nearly four years of follow-up. We emphasise the benefit of a timely diagnosis and intervention which were the keys to success in this case.

Mycorrhizal Colonization of Wheat by Intact Extraradical Mycelium of Mn-Tolerant Native Plants Induces Different Biochemical Mechanisms of Protection.

Soil with excess Mn induces toxicity and impairs crop growth. However, with the development in the soil of an intact extraradical mycelia (ERM) from arbuscular mycorrhizal fungi (AMF) symbiotic to native Mn-tolerant plants, wheat growth is promoted due to a stronger AMF colonization and subsequent increased protection against Mn toxicity. To determine the biochemical mechanisms of protection induced by this native ERM under Mn toxicity, wheat grown in soil from previously developed Lolium rigidum (LOL) or Ornithopus compressus (ORN), both strongly mycotrophic plants, was compared to wheat grown in soil from previously developed Silene gallica (SIL), a non-mycotrophic plant. Wheat grown after LOL or ORN had 60% higher dry weight, ca. two-fold lower Mn levels and almost double P contents. Mn in the shoots was preferentially translocated to the apoplast along with Mg and P. The activity of catalase increased; however, guaiacol peroxidase (GPX) and superoxide dismutase (SOD) showed lower activities. Wheat grown after ORN differed from that grown after LOL by displaying slightly higher Mn levels, higher root Mg and Ca levels and higher GPX and Mn-SOD activities. The AMF consortia established from these native plants can promote distinct biochemical mechanisms for protecting wheat against Mn toxicity.

Influence of Intact Mycelium of Arbuscular Mycorrhizal Fungi on Soil Microbiome Functional Profile in Wheat under Mn Stress.

In the current agronomic context, the adoption of alternative forms of soil management is essential to increase crop yield. Agricultural sustainability requires practices that generate positive impacts and promote an increase in microbiome diversity as a tool to overcome adverse environmental conditions. An important ally is the indigenous arbuscular mycorrhizal fungi (AMF) that can improve plant growth and provide protection against abiotic stress such as metal toxicity. In a greenhouse experiment, this work studied the effect of wheat growth on several parameters of biological activity and functional microbiome in relation to wheat antecedent plant mycotrophy and soil disturbance under Mn stress. When the wheat was planted after highly mycotrophic plants and the soil was not previously disturbed, the results showed a 60% increase in wheat arbuscular colonization and a 2.5-fold increase in dry weight along with higher values of photosynthetic parameters and dehydrogenase activity. Conversely, soil disturbance before wheat planting increased the ß-glucosidase activity and the count of manganese oxidizers, irrespectively of antecedent plant, and decreased drastically the wheat dry weight, the AMF colonization and the chlorophyll content compared to the undisturbed treatment. These findings suggest that not only the wheat growth but also the soil functional microbiome associated is affected by the antecedent type of plant and previous soil disturbance imposed. In addition, the improvement in wheat dry weight despite Mn toxicity may rely on shifts in biological activity associated to a well-established and intact ERM early developed in the soil.

[Rooming-in, Breastfeeding and Neonatal Follow-up of Infants Born to Mothers with COVID-19]. / Alojamento Conjunto, Amamentação e Seguimento Neonatal de Recém-Nascidos de Mãe com COVID-19.

INTRODUCTION: Due to growing evidence suggesting COVID-19 may have a benign course in the newborn, a number of guidelines supporting rooming-in and breastfeeding were developed. The main aim of the study was to assess the safety of this approach, through the risk of developing severe neonatal infection. MATERIAL AND METHODS: Prospective observational study from April 2020 to February 2021 on the approach and neonatal follow-up of infants born to mothers with COVID-19 at the time of delivery in a hospital with advanced neonatal care, where rooming in and breastfeeding were promoted whenever possible. We collected data during hospital admission and over the phone during the neonatal period. RESULTS: We included 77 infants born to mothers with COVID-19 (3.8% of newborns born during the time of study), median gestational age 39 weeks + 5 days and median birth weight 3270 g; 9% were born premature (versus 12% born premature among newborns born during the time of study). Rooming-in took place in all of them although 4% were briefly admitted to the Neonatal Intensive Care Unit; 88% were discharged home up to day three, 97% were breastfed at the time of discharge and 90% were still breastfed by the end of the neonatal period. We completed neonatal follow-up of 63 newborns, eight of them developed COVID-associated symptoms, three with need of medical evaluation; 40% had no medical assessment after being discharged. Out of 77, 5% of infants were infected with SARS-CoV-2 (total of four, one mild, three asymptomatic), with no significant differences during hospital stay or follow-up. DISCUSSION: Neonatal infection was uncommon and mild, and there was no increase in prematurity. Rooming-in and breastfeeding were safe and should be promoted whenever clinically possible. Follow-up care after hospital discharge needs improvement. CONCLUSION: Infants born to mothers with COVID-19 were safely roomed in with their mothers and exclusively breastfed.

Introdução: Dada a evidência crescente de maior benignidade da COVID-19 no recém-nascido, surgiram recomendações de promoção do alojamento conjunto e da amamentação. O principal objetivo do estudo foi avaliar a segurança dessa abordagem, através do risco de infeção neonatal grave.Material e Métodos: Estudo observacional prospetivo de abril 2020 a fevereiro 2021 da abordagem hospitalar e seguimento após a alta dos recém-nascidos de mãe com COVID-19 num hospital com apoio perinatal diferenciado, onde foram advogados o alojamento conjunto e amamentação, sempre que possível. Recolhemos os dados no internamento e em seguimento telefónico durante o período neonatal.Resultados: Incluímos 77 recém-nascidos de mãe com COVID-19 (3,8% do total de recém-nascidos), com medianas de idade gestacional 39 semanas e 5 dias e 2370 g de peso à nascença; destes, 9% nasceram pré-termos (versus 12% pré-termos no total de recém-nascidos). Todos estiveram em alojamento conjunto e 4% foram admitidos transitoriamente na Unidade de Cuidados Intensivos Neonatais; um total de 88% recém-nascidos tiveram alta até ao terceiro dia de vida, 97% tiveram alta sob aleitamento materno e 90% mantinham-no no fim do período neonatal. Dos 63 recém-nascidos com seguimento telefónico completo, oito tiveram sintomas compatíveis com COVID-19, três dos quais com observação médica. Em 40% dos casos não houve consulta médica de vigilância após a alta. Houve 5% recém-nascidos com COVID-19 (num total de quatro, registámos um quadro ligeiro e três assintomáticos), sem particularidades no internamento ou seguimento.Discussão: A infeção neonatal foi incomum, não houve quadros graves nem maior incidência de prematuridade. O alojamento conjunto e a amamentação foram práticas seguras, devendo ser promovidas desde que clinicamente possível. Destacamos que a vigilância de saúde após a alta necessita de ser melhorada.Conclusão: Os recém-nascidos de mãe com COVID-19 podem ser mantidos em alojamento conjunto e sob aleitamento materno exclusivo.

Effect of Tillage System and Cover Crop on Maize Mycorrhization and Presence of Magnaporthiopsis maydis.

The sustainability of agriculture requires the adoption of agricultural soil conservation practices with positive impacts on soil quality, which can promote beneficial soil microbiota like arbuscular mycorrhizal fungi (AMF) and its diversity. This study aims to assess the influence of the presence of intact extraradical mycelium as a preferential source of inoculum of the native AMF in order to guarantee a better colonization as well as its possible bioprotective effect against Magnaporthiopsis maydis. In order to vary the available extraradical mycelium, two experiments, with and without cover crop, were carried out, in which two tillage systems and two maize varieties were studied. The capitalization of the benefits, in terms of grain production and M. maydis presence, associated to the cover crop were only achieved with minimum tillage. Therefore, both cultural practices are necessary to reduce the fungus presence, coupling the effect of mycorrhization together with other benefits associated with the cover crop. Although in the absence of a cover crop and using conventional tillage, yields and lower levels of M. maydis are possibly achieved, this system is more dependent on the variety used, does not benefit from the advantages associated with the cover crop, is more expensive, and environmentally unsustainable.

BAC array CGH distinguishes mutually exclusive alterations that define clinicogenetic subtypes of gliomas.

The pathological classification of gliomas constitutes a critical step of the clinical management of patients, yet it is frequently challenging. To assess the relationship between genetic abnormalities and clinicopathological characteristics, we have performed a genetic and clinical analysis of a series of gliomas. A total of 112 gliomas were analyzed by comparative genomic hybridization on a BAC array with a 1 megabase resolution. Altered regions were identified and correlation analysis enabled to retrieve significant associations and exclusions. Whole chromosomes (chrs) 1p and 19q losses with centromeric breakpoints and EGFR high level amplification were found to be mutually exclusive, permitting identification of 3 distinct, nonoverlapping groups of tumors with striking clinicopathological differences. Type A tumors with chrs 1p and 19q co-deletion exhibited an oligodendroglial phenotype and a longer patient survival. Type B tumors were characterized by EGFR amplification. They harbored a WHO high grade of malignancy and a short patient survival. Finally, type C tumors displayed none of the previous patterns but the presence of chr 7 gain, chr 9p deletion and/or chr 10 loss. It included astrocytic tumors in patients younger than in type B and whose prognosis was highly dependent upon the number of alterations. A multivariate analysis based on a Cox model shows that age, WHO grade and genomic type provide complementary prognostic informations. Finally, our results highlight the potential of a whole-genome analysis as an additional diagnostic in cases of unclear conventional genetic findings.

CAPweb: a bioinformatics CGH array Analysis Platform.

Assessing variations in DNA copy number is crucial for understanding constitutional or somatic diseases, particularly cancers. The recently developed array-CGH (comparative genomic hybridization) technology allows this to be investigated at the genomic level. We report the availability of a web tool for analysing array-CGH data. CAPweb (CGH array Analysis Platform on the Web) is intended as a user-friendly tool enabling biologists to completely analyse CGH arrays from the raw data to the visualization and biological interpretation. The user typically performs the following bioinformatics steps of a CGH array project within CAPweb: the secure upload of the results of CGH array image analysis and of the array annotation (genomic position of the probes); first level analysis of each array, including automatic normalization of the data (for correcting experimental biases), breakpoint detection and status assignment (gain, loss or normal); validation or deletion of the analysis based on a summary report and quality criteria; visualization and biological analysis of the genomic profiles and results through a user-friendly interface. CAPweb is accessible at http://bioinfo.curie.fr/CAPweb.

The major ß-catenin/E-cadherin junctional binding site is a primary molecular mechano-transductor of differentiation in vivo.

In vivo, the primary molecular mechanotransductive events mechanically initiating cell differentiation remain unknown. Here we find the molecular stretching of the highly conserved Y654-ß-catenin-D665-E-cadherin binding site as mechanically induced by tissue strain. It triggers the increase of accessibility of the Y654 site, target of the Src42A kinase phosphorylation leading to irreversible unbinding. Molecular dynamics simulations of the ß-catenin/E-cadherin complex under a force mimicking a 6 pN physiological mechanical strain predict a local 45% stretching between the two α-helices linked by the site and a 15% increase in accessibility of the phosphorylation site. Both are quantitatively observed using FRET lifetime imaging and non-phospho Y654 specific antibody labelling, in response to the mechanical strains developed by endogenous and magnetically mimicked early mesoderm invagination of gastrulating Drosophila embryos. This is followed by the predicted release of 16% of ß-catenin from junctions, observed in FRAP, which initiates the mechanical activation of the ß-catenin pathway process.

VAMP: visualization and analysis of array-CGH, transcriptome and other molecular profiles.

MOTIVATION: Microarray-based CGH (Comparative Genomic Hybridization), transcriptome arrays and other large-scale genomic technologies are now routinely used to generate a vast amount of genomic profiles. Exploratory analysis of this data is crucial in helping to understand the data and to help form biological hypotheses. This step requires visualization of the data in a meaningful way to visualize the results and to perform first level analyses. RESULTS: We have developed a graphical user interface for visualization and first level analysis of molecular profiles. It is currently in use at the Institut Curie for cancer research projects involving CGH arrays, transcriptome arrays, SNP (single nucleotide polymorphism) arrays, loss of heterozygosity results (LOH), and Chromatin ImmunoPrecipitation arrays (ChIP chips). The interface offers the possibility of studying these different types of information in a consistent way. Several views are proposed, such as the classical CGH karyotype view or genome-wide multi-tumor comparison. Many functionalities for analyzing CGH data are provided by the interface, including looking for recurrent regions of alterations, confrontation to transcriptome data or clinical information, and clustering. Our tool consists of PHP scripts and of an applet written in Java. It can be run on public datasets at http://bioinfo.curie.fr/vamp AVAILABILITY: The VAMP software (Visualization and Analysis of array-CGH,transcriptome and other Molecular Profiles) is available upon request. It can be tested on public datasets at http://bioinfo.curie.fr/vamp. The documentation is available at http://bioinfo.curie.fr/vamp/doc.

Hypoxia and estrogen co-operate to regulate gene expression in T-47D human breast cancer cells.

Experimental and clinical studies have shown that both estrogen (E2) and hypoxia (H) are involved in tumor development and progression. A study was undertaken to determine whether these factors could interact to modulate gene expression using a microarray approach. We screened the transcript levels of over 8000 genes in the estrogen receptor (ERalpha) positive T-47D human breast cancer cell lines maintained at 21% O2 or 1% O2 with or without E2 co-treatment. Treatment by E2 or hypoxia alone altered the expression of 26 and 9 genes, respectively, whilst the expression of 31 genes was modulated by the H-E2 combination. The majority (21/31 genes) underwent a down-regulation. Microarray data was validated for 19 by quantitative real-time PCR and a good correlation noted (r2=0.8). Five out of these 19 genes were assayed for protein expression by Western blot. A correlation was also found between mRNA and protein levels. Statistical analysis showed that the gene expression modulation by the combined H and E2 treatment was additive in most cases, but for RasGRP2 and transferrin (TF) an antagonistic interaction was noted. The results demonstrate that hypoxic conditions and estrogen exposure interact to modulate the expression of a limited number of genes involved in cell growth and differentiation, angiogenesis, protein transport, metabolism and apoptosis.

Spatial normalization of array-CGH data.

BACKGROUND: Array-based comparative genomic hybridization (array-CGH) is a recently developed technique for analyzing changes in DNA copy number. As in all microarray analyses, normalization is required to correct for experimental artifacts while preserving the true biological signal. We investigated various sources of systematic variation in array-CGH data and identified two distinct types of spatial effect of no biological relevance as the predominant experimental artifacts: continuous spatial gradients and local spatial bias. Local spatial bias affects a large proportion of arrays, and has not previously been considered in array-CGH experiments. RESULTS: We show that existing normalization techniques do not correct these spatial effects properly. We therefore developed an automatic method for the spatial normalization of array-CGH data. This method makes it possible to delineate and to eliminate and/or correct areas affected by spatial bias. It is based on the combination of a spatial segmentation algorithm called NEM (Neighborhood Expectation Maximization) and spatial trend estimation. We defined quality criteria for array-CGH data, demonstrating significant improvements in data quality with our method for three data sets coming from two different platforms (198, 175 and 26 BAC-arrays). CONCLUSION: We have designed an automatic algorithm for the spatial normalization of BAC CGH-array data, preventing the misinterpretation of experimental artifacts as biologically relevant outliers in the genomic profile. This algorithm is implemented in the R package MANOR (Micro-Array NORmalization), which is described at http://bioinfo.curie.fr/projects/manor and available from the Bioconductor site http://www.bioconductor.org. It can also be tested on the CAPweb bioinformatics platform at http://bioinfo.curie.fr/CAPweb.

El enfrentamiento a la covid-19 en servicios estomatológicos cubanos / Facing COVID-19 in Cuban Dentistry Services

RESUMEN El escenario estomatológico, si no se aplican adecuadamente los protocolos de protección, constituye una importante fuente de infección cruzada entre pacientes y profesionales de la Estomatología. Muchos son los microorganismos involucrados, y a esto se ha incorporado recientemente el SARS-CoV-2. Al tener en cuenta la letalidad mundial de esta enfermedad, es imprescindible reconsiderar si las medidas de bioseguridad establecidas son estrictas y eficaces para evitar su propagación. Fue realizada esta investigación con el objetivo de actualizar información relacionada con la presente pandemia y los modos de actuación que propicien una consulta estomatológica segura en tiempos de COVID-19 (AU).

ABSTRACT The dentistry setting is an important crossed infection source among patients and Dentistry professionals if the protection protocols are not adequately applied. There are many microorganisms involved, and recently SARS-CoV-2 has added to them. When taking into account the worldwide lethality of this disease, it is bare essential reconsidering if the stablished biosafety measures are strict and efficacious to avoid spread. A thematic update was carried out with the aim of updating the information related to current pandemic and the ways of acting propitiating a safe Dentistry consultation in times of COVID-19 (AU).

Cuidados en los servicios de Prótesis frente a la pandemia por covid-19 / Cares in the Prosthetic services toward COVID-19 pandemic

RESUMEN La covid-19 es una enfermedad infecciosa causada por el virus SARS-CoV-2, y es capaz de provocar un cuadro clínico variable. Los individuos que están en contacto estrecho con pacientes positivos de esta enfermedad, tienen un mayor riesgo de infección. Así les sucede a los trabajadores de la salud que atienden directamente a pacientes. Al igual que otros servicios de salud, la atención estomatológica requiere del contacto estrecho entre el profesional y el paciente. El objetivo de este trabajo fue describir las principales recomendaciones para la prevención y control de infecciones por SARS-CoV-2 en los servicios de Prótesis. En la práctica dental, la prevención, el control y la reducción de la transmisión de infecciones se realiza a través del uso del equipo de protección personal y de un conjunto de procedimientos de descontaminación, desinfección y esterilización en cualquier superficie o instrumento. La constante actualización científica y la adopción de medidas de protección antes, durante y después de la atención estomatológica, podrán garantizar el éxito de la atención médica con el mínimo riesgo de contagio (AU).

ABSTRACT COVID-19 is an infectious diseases caused by SARS-CoV-2 virus, and it is able to provoke variable clinical characteristics. The individuals that are in close contact with this disease positive patients are at higher infection risk. That is the case of the heath care workers directly caring for patients. As in any health service, dentistry care requires the narrow contact between the professional and the patient. The aim of this paper was describing the main recommendations for preventing and control SARS-CoV-2 in Prosthetic services. In the dental practice, the prevention, control and reduction of infection transmission is achieved using the personal protection equipment and a whole of decontamination, disinfection and sterilization procedures in any surface or device. The constant scientific updating and adopting protection measures before, during and after the dentistry care can ensure the success of health care with the minimal risk of contagion (AU).

Habilidades investigativas en estudiantes del ciclo clínico de la carrera de Estomatología / Research skills in students of the clinical cycle of Stomatology pre-graduate studies

RESUMEN Introducción: las habilidades investigativas se insertan en la formación del profesional de estomatología como una de las dimensiones claves del proceso de formación. Objetivo: evaluar la percepción de los estudiantes acerca del estado actual de desarrollo de las habilidades investigativas en el ciclo clínico de la carrera de Estomatología de la Universidad de Ciencias Médicas de Matanzas. Materiales y métodos: se realizó una investigación descriptiva, de corte transversal, en la que participaron 68 estudiantes de tercer a quinto año, durante la culminación del curso 2018-2019. Fueron seleccionados a través de un muestreo intencional. Se empleó un cuestionario de percepción del dominio de las habilidades relacionadas con el manejo de la información científica, el diseño y ejecución de investigaciones, y el análisis de situación de salud bucal. Resultados: los estudiantes reconocieron tener dominio de la habilidad para el manejo de la información científica y para el análisis de situación de salud bucal. Las acciones menos dominadas fueron la recopilación de información y el diseño de un perfil de proyecto de investigación. La Jornada Científica Estudiantil y el trabajo de curso fueron las vías más empleadas para la divulgación científica. Predominaron los obstáculos externos, seguidos de obstáculos asociados al propio dominio de la habilidad para el diseño y la ejecución de la investigación científica. Conclusión: los estudiantes del ciclo clínico de la carrera de Estomatología reconocen poseer un adecuado dominio de las habilidades investigativas, lo cual contribuye de modo satisfactorio a la formación profesional. No obstante, resulta necesario promover acciones educativas que tributen a las operaciones menos dominadas y estimulen la inserción estudiantil en proyectos de investigación para la sistematización de estas habilidades (AU).

ABSTRACT Introduction: research skills are inserted in the training of the stomatology professional as one of the key dimensions of the training process. Objective: to evaluate the perception of students about the current state of development of research skills in the clinical cycle of the pre-graduate studies of Stomatology of the University of Medical Sciences of Matanzas. Materials and methods: a descriptive, cross-sectional research was carried out, involving 68 third to fifth year students, during the co a descriptive, cross-sectional research was carried out, involving 68 third to fifth year students, during the completion of the 2018-2019 course. They were chosen through intentional sampling. A perception questionnaire was used for the mastering skills related to the management of scientific information, the design and execution of research, and oral health situation analysis. Results: the students recognized to master the ability of handling scientific information and oral health situation analysis. Less mastered actions were the collection of information and the design of a research project profile. The Student Science Day and the course work were the most widely used ways for scientific dissemination. External difficulties predominated, followed by difficulties associated with the own mastery of the ability to design and execute scientific research. Conclusion: the students in the clinical cycle of the pre-grade studies of Stomatology recognize having an adequate mastery of research skills, which contributes satisfactorily to professional training. However, it is necessary to promote educational actions that contribute to the less dominated operations and stimulate the insertion of students in research projects for the systematization of these skills (AU).

Tratamiento de Ortodoncia en un paciente con síndrome de Down / The Orthodontics treatment in a patient with Down syndrome

RESUMEN El tratamiento de Ortodoncia en pacientes con síndrome de Down, ha sido un tema debatido durante muchos años por los especialistas debido a las deficiencias físicas, mentales y a la dificultad de estos en la cooperación con el tratamiento. El objetivo de este trabajo es mostrar resultados adecuados de tratamiento ortodóncico en una paciente femenina de 12 años de edad con síndrome de Down. La niña acudió a consulta acompañada de su mamá y de su abuela solicitando tratamiento por presentar los dientes virados. En el examen clínico se observó rotación marcada de 11 y 21 mayor de 900 que afecta su estética facial. Se explicó a la familia lo difícil que podía resultar el tratamiento a esta adolescente con necesidades especiales, a la que habría que aplicar una fuerza ortodóncica que genera marcada molestia y pudiera presentarse una escasa tolerancia al dolor. La familia aseguró su cooperación. Se decidió emprender la terapia para lo cual se diseñó un plan de tratamiento en dos etapas. En una primera etapa se empleó aparatología ortodóncica removible y en una segunda etapa aparatología fija. Al concluir el tratamiento se logró resolver de manera satisfactoria el motivo de consulta con buena cooperación por parte de la paciente y su familia. El éxito del tratamiento se debió a la satisfactoria cooperación de la paciente y al establecimiento de una relación favorable ortodoncista-paciente-familia (AU).

ABSTRACT The Orthodontics treatment in patients with Down syndrome has being a theme debated by specialist during many years, due to the physical and mental deficiencies of this kind of patients and their difficulty in cooperating with the treatment. The aim of this article is showing the adequate results of the orthodontic treatment in a female patient aged 12 years with Down syndrome. The girl assisted to consultation with her mother and grandmother asking treatment for having crooked teeth. At the physical examination it was observed a remarked rotation of 11 and 21 of more than 900, affecting her facial esthetics. Doctors explained to relatives that the treatment could result very difficult to this teenager with special requirements due to the application of an orthodontic force generating great discomfort in this girl, possibly having a scarce tolerance to pain. The relatives agreed to cooperate. They decided to start the therapy, and a two-stage plan was designed. In the first stage, removable orthodontic braces were used, and fixed ones were used in the second stage. At the end of the treatment the cause of the consultation was successfully solved with a good cooperation of the patient and her relatives. The success of the treatment was achieved due to the satisfactory cooperation of the patient and the establishment of a favorable relationship orthodontist-patient-family (AU).

Distancia intercanina en niños con dentición temporal, mixta y permanente / Intercanine distance in children with temporary, mixed and permanent dentition

RESUMEN Introducción: Los valores de la distancia intercanina representan una referencia auxiliar útil, para predecir problemas de deficiencia de espacio relacionados con el crecimiento transversal de los maxilares. Objetivo: Determinar los valores de la distancia intercanina en niños con oclusión normal en ambas arcadas dentarias y distintos períodos de dentición. Métodos: Fue realizado un estudio de tipo descriptivo y transversal. El universo estuvo comprendido por 6 033 escolares, de los cuales se obtuvo una muestra aleatoria estratificada de 525 niños con edades de 3, 6, 9 y 12 años, seleccionados de acuerdo con las etapas de desarrollo dental: dentición temporal, mixta temprana, tardía y permanente. Fue realizado un examen clínico facial y bucal, para lo cual se aplicaron los criterios de inclusión. Las variables fueron: edad, sexo y distancia intercanina superior e inferior. Para valorar la posible existencia de asociación entre la distancia intercanina y el sexo, así como con la edad, se utilizó la prueba t de Student para muestras independientes y el análisis de varianza (ANOVA), respectivamente. Resultados: La distancia intercanina superior a los 3 años fue: 27,3 mm, 6 años: 30,42 mm, 9 años: 31,67 y 12 años: 32,93 mm, e inferior (23,19 mm, 24,66 mm, 25,61 y 25,98 mm) para los 3, 6, 9, y 12 años, respectivamente. El sexo masculino mostró los mayores valores. Se comprobaron diferencias significativas en relación con el sexo en la distancia intercanina superior a los 6 y 12 años (p= 0,000) y en la inferior en las mismas edades (p= 0,001 y p=0,01), entre las edades (p= 0,000) tanto en superior como inferior. Conclusiones: La distancia intercanina se incrementa en ambos maxilares conjuntamente con la edad. Se comprueba un predominio de mayor anchura del sexo masculino a los 6 y 12 años en ambos maxilares(AU)

ABSTRACT Introduction: Intercanine distance values are a useful auxiliary reference to predict space deficiency problems related to transverse maxillary growth. Objective: Determine intercanine distance values for children with normal occlusion in both dental arches during the different dentition periods. Methods: A descriptive, cross-sectional study was conducted. The study universe was 6 033 schoolchildren, from whom a stratified random sample was selected of 525 children aged 3, 6, 9 and 12 years, corresponding to the stages of dental development: temporary, early mixed, late mixed and permanent dentition. Facial and oral clinical examination was performed, based on the inclusion criteria. The variables studied were age, sex, upper intercanine distance and lower intercanine distance. The possible association between intercanine distance and sex and age was determined with Student's independent samples t-test and analysis of variance (ANOVA), respectively. Results: Upper intercanine distance was 27.3 mm at 3 years, 30.42 mm at 6 years, 31.67 mm at 9 years and 32.93 mm at 12 years. Lower intercanine distance was 23.19 mm, 24.66 mm, 25.61 mm and 25,98 mm at 3, 6, 9 and 12 years, respectively. Male subjects exhibited greater values. Significant differences were found with respect to sex in upper intercanine distance at 6 and 12 years (p= 0.000) and in lower intercanine distance at the same ages (p= 0.001 and p=0.01), as well as in upper and lower intercanine distance across the different ages (p= 0.000). Conclusions: Intercanine distance increases in both jaws with age. A predominance was found of a greater width in the male sex in both jaws at 6 and 12 years of age(AU)

Proteomic screening identifies a YAP-driven signaling network linked to tumor cell proliferation in human schwannomas.

BACKGROUND: Inactivation of the NF2 gene predisposes to neurofibromatosis type II and the development of schwannomas. In vitro studies have shown that loss of NF2 leads to the induction of mitogenic signaling mediated by receptor tyrosine kinases (RTKs), MAP kinase, AKT, or Hippo pathways. The goal of our study was to evaluate the expression and activity of these signaling pathways in human schwannomas in order to identify new potential therapeutic targets. METHODS: Large sets of human schwannomas, totaling 68 tumors, were analyzed using complementary proteomic approaches. RTK arrays identified the most frequently activated RTKs. The correlation between the expression and activity of signaling pathways and proliferation of tumor cells using Ki67 marker was investigated by reverse-phase protein array (RRPA). Finally, immunohistochemistry was used to evaluate the expression pattern of signaling effectors in the tumors. RESULTS: We showed that Her2, Her3, PDGFRß, Axl, and Tie2 are frequently activated in the tumors. Furthermore, RRPA demonstrated that Ki67 levels are linked to YAP, p-Her3, and PDGFRß expression levels. In addition, Her2, Her3, and PDGFRß are transcriptional targets of Yes-associated protein (YAP) in schwannoma cells in culture. Finally, we observed that the expression of these signaling effectors is very variable between tumors. CONCLUSIONS: Tumor cell proliferation in human schwannomas is linked to a signaling network controlled by the Hippo effector YAP. Her2, Her3, PDGFRß, Axl, and Tie2, as well as YAP, represent potentially valuable therapeutic targets. However, the variability of their expression between tumors may result in strong differences in the response to targeted therapy.