Complicaciones relacionadas a la contención fija en ortodoncia:"Efecto giro". Revisión Bibliográfica

Las contenciones fijas en ortodoncia han demostrado tener excelentes resultados para la estabilidad y durabilidad del tratamiento. A pesar de esto, se ha observado que existen ciertos movimientos dentarios indeseados totalmente diferentes a una recidiva a su posición inicial previa al tratamiento de ortodoncia. El llamado "efecto giro" es uno de ellos, y se caracteriza por ser una inclinación en sentidos opuestos de los caninos contralaterales, en donde uno presenta una inclinación hacia vestibular y el otro hacia lingual o palatino. Se presenta principalmente en la mandíbula, a pesar de que la contención permanece perfectamente adherida a los dientes. El objetivo de esta revisión bibliográfica es evaluar los distintos factores reportados en la literatura que puedan estar relacionados con la aparición del "efecto giro" y qué tan relevantes pueden ser en su desarrollo. Como conclusión es importante considerar el carácter multifactorial de este tipo de complicaciones, en donde el tipo y calidad del alambre que se utilice para la contención, junto con las características periodontales del paciente demostraron tener cierta participación en la génesis de este, por lo tanto, resulta fundamental concientizar a los pacientes de la importancia de los controles ortodóncicos periódicos posteriores al retiro de los aparatos fijos para monitorear y controlar los resultados oclusales logrados y el estado de los dispositivos de contención instalados.

As contenções fixas em ortodontia têm demonstrado excelentes resultados para a estabilidade e durabilidade do tratamento. Apesar disso, observou-se que existem certos movimentos dentários indesejados totalmente diferentes de uma recorrência à sua posição inicial anterior ao tratamento ortodôntico. O chamado "efeito de torção" é um deles, e se caracteriza por uma inclinação em sentidos opostos dos caninos contralaterais, onde um apresenta uma inclinação para vestibular e outro para lingual ou palatino. Ocorre principalmente na mandíbula, apesar do retentor permanecer perfeitamente preso aos dentes. O objetivo desta revisão bibliográfica é avaliar os diferentes fatores relatados na literatura que podem estar relacionados ao aparecimento do "efeito turn" e quão relevantes podem ser no seu desenvolvimento. Em conclusão, é importante considerar a natureza multifatorial deste tipo de complicações, onde o tipo e a qualidade do fio utilizado para contenção, juntamente com as características periodontais do paciente, mostraram algum envolvimento na sua génese, pelo que é essencial conscientizar os pacientes sobre a importância de check-ups ortodônticos periódicos após a remoção dos aparelhos fixos para monitorar e controlar os resultados oclusais alcançados e o estado dos dispositivos de contenção instalados.

Neumomediastino secundario a fractura aislada de piso de órbita / Pneumomediastinum secondary to isolated fracture of orbit floorx

Resumen Introducción: El neumomediastino se define como la presencia de aire o gas dentro de los planos fasciales del mediastino. Por lo general, es un fenómeno secundario a perforaciones traumáticas del tracto aerodigestivo. El neumomediastino secundario a una fractura orbitaria es un evento raro. Se asocia a complicaciones potencialmente mortales como el neumotórax, el neumopericardio y la mediastinitis. Objetivo: Describir un caso de neumomediastino secundario a una fractura aislada de piso orbitario y su manejo médico-quirúrgico. Caso clínico: Paciente de sexo femenino de 42 años que sufre traumatismo en regiones facial, cervical y torácica desarrollando secundariamente un enfisema subcutáneo panfacial y un neumomediastino, el cual se resuelve exitosamente. Discusión: El neumomediastino secundario a una fractura aislada de piso orbitario es un evento muy raro. El aire puede descender a lo largo de los espacios fasciales hasta el mediastino. En este sentido, sonarse la nariz es un factor de riesgo para desarrollar esta pa-tología. Conclusión: Ocurrido un trauma maxilofacial puede presentarse enfisemas de espacios profundos de la cabeza, cuello e incluso el mediastino.

Introduction: Pneumomediastinum is defined as the presence of air or gas within the fascial planes of the mediastinum. It is usually a phenomenon secondary to traumatic perforations of the aerodigestive tract. Pneumomediastinum secondary to an orbital fracture is a rare event. And it is related to life-threatening complications such as pneumothorax, pneumopericardium and mediastinitis. Aim: To describe a case of pneumomediastinum secondary to an isolated orbital floor fracture and its medical-surgical management. Clinical case: A 42-year-old female patient who suffers trauma to the facial, cervical and thoracic regions, secondary development of a subcutaneous panfacial emphysema and pneumomediastinum, which resolves successfully. Discussion: Pneumomediastinum following an isolated orbital floor fracture is a very rare event. The air can descend along the fascial spaces to the mediastinum. In this sense, blowing your nose is a risk factor to develop this pathology. Conclusion: After a maxillofacial trauma, emphysema of the deep spaces of the head, neck and even the mediastinum can occur

Imaging low-mass planets within the habitable zone of α Centauri.

Giant exoplanets on wide orbits have been directly imaged around young stars. If the thermal background in the mid-infrared can be mitigated, then exoplanets with lower masses can also be imaged. Here we present a ground-based mid-infrared observing approach that enables imaging low-mass temperate exoplanets around nearby stars, and in particular within the closest stellar system, α Centauri. Based on 75-80% of the best quality images from 100 h of cumulative observations, we demonstrate sensitivity to warm sub-Neptune-sized planets throughout much of the habitable zone of α Centauri A. This is an order of magnitude more sensitive than state-of-the-art exoplanet imaging mass detection limits. We also discuss a possible exoplanet or exozodiacal disk detection around α Centauri A. However, an instrumental artifact of unknown origin cannot be ruled out. These results demonstrate the feasibility of imaging rocky habitable-zone exoplanets with current and upcoming telescopes.

Mediastinitis necrotizante descendente de origen odontogénico / Descending necrotizing mediastinitis of odontogenic origin

Resumen Introducción: El tratamiento inoportuno e ineficaz de las infecciones odontogénicas puede causar complicaciones potencialmente mortales como la mediastinitis necrotizante descendente (MND). La MDN es una infección grave que afecta al cuello-tórax, con una alta tasa de mortalidad por sepsis e insuficiencia orgánica si no se trata de manera rápida y efectiva. Objetivo: Describir un caso de MND de origen odontogénico y su manejo médico-quirúrgico. Caso clínico: Presentamos un paciente de sexo masculino de 34 años que ingresa con un cuadro infeccioso agudo de origen odontogénico, que compromete espacios de la cabeza, cuello y tórax (mediastino superior), el cual se trata exitosamente. Discusión: Las infecciones odontogénicas son generalmente localizadas y que se pueden tratar mediante terapias convencionales. A pesar de esto, si estas infecciones no pueden controlarse, ya sea por no realización de tratamientos oportunos o por estados inmunosuprimidos del paciente, se pueden desarrollar diferentes complicaciones como la MND. Conclusión: Un diagnóstico rápido, el tratamiento quirúrgico agresivo, la terapia antibiótica adecuada y la atención de apoyo son los pilares fundamentales para el manejo de la MND.

Introduction: Inappropriate and ineffective treatment of odontogenic infections can cause life-threatening complications such as Descending Necrotizing Mediastinitis (MND). MDN is a serious infection that affects the neck-thorax, with a high mortality rate from sepsis and organ failure if it is not treated quickly and effectively. Aim: To describe a case of MND of odontogenic origin and its medical-surgical management. Case report: We present a 34-year-old male patient who is admitted with an acute infectious condition of odontogenic origin, which compromises spaces of the head, neck and thorax (upper mediastinum), which is treated successfully. Discussion: Odontogenic infections are generally localized and can be treated by conventional therapies. In spite of this, if these infections cannot be controlled, either by not carrying out appropriate treatments or by immunosuppressed states of the patient, different complications such as MND can develop. Conclusion: A rapid diagnosis, aggressive surgical treatment, adequate antibiotic therapy and supportive care are the fundamental pillars for the management of MND.

Making sense of parameter estimation and model simulation in bioprocesses.

Most articles that report fitted parameters for kinetic models do not include meaningful statistical information. This study demonstrates the importance of reporting a complete statistical analysis and shows a methodology to perform it, using functionalities implemented in computational tools. As an example, alginate production is studied in a batch stirred-tank fermenter and modeled using the kinetic model proposed by Klimek and Ollis (1980). The model parameters and their 95% confidence intervals are estimated by nonlinear regression. The significance of the parameters value is checked using a hypothesis test. The uncertainty of the parameters is propagated to the output model variables through prediction intervals, showing that the kinetic model of Klimek and Ollis (1980) can simulate with high certainty the dynamic of the alginate production process. Finally, the results obtained in other studies are compared to show how the lack of statistical analysis can hold back a deeper understanding about bioprocesses.

Polymorphisms within the ARNT2 and CX3CR1 Genes Are Associated with the Risk of Developing Invasive Aspergillosis.

Invasive aspergillosis (IA) is a life-threatening infection that affects an increasing number of patients undergoing chemotherapy or allo-transplantation, and recent studies have shown that genetic factors contribute to disease susceptibility. In this two-stage, population-based, case-control study, we evaluated whether 7 potentially functional single nucleotide polymorphisms (SNPs) within the ARNT2 and CX3CR1 genes influence the risk of IA in high-risk hematological patients. We genotyped selected SNPs in a cohort of 500 hematological patients (103 of those had been diagnosed with proven or probable IA), and we evaluated their association with the risk of developing IA. The association of the most interesting markers of IA risk was then validated in a replication population, including 474 subjects (94 IA and 380 non-IA patients). Functional experiments were also performed to confirm the biological relevance of the most interesting markers. The meta-analysis of both populations showed that carriers of the ARNT2rs1374213G, CX3CR1rs7631529A, and CX3CR1rs9823718G alleles (where the RefSeq identifier appears as a subscript) had a significantly increased risk of developing IA according to a log-additive model (P value from the meta-analysis [PMeta] = 9.8 · 10-5, PMeta = 1.5 · 10-4, and PMeta =7.9 · 10-5, respectively). Haplotype analysis also confirmed the association of the CX3CR1 haplotype with AG CGG with an increased risk of IA (P = 4.0 · 10-4). Mechanistically, we observed that monocyte-derived macrophages (MDM) from subjects carrying the ARNTR2rs1374213G allele or the GG genotype showed a significantly impaired fungicidal activity but that MDM from carriers of the ARNT2rs1374213G and CX3CR1rs9823718G or CX3CR1rs7631529A alleles had deregulated immune responses to Aspergillus conidia. These results, together with those from expression quantitative trait locus (eQTL) data browsers showing a strong correlation of the CX3CR1rs9823718G allele with lower levels of CX3CR1 mRNA in whole peripheral blood (P = 2.46 · 10-7) and primary monocytes (P = 4.31 · 10-7), highlight the role of the ARNT2 and CX3CR1 loci in modulating and predicting IA risk and provide new insights into the host immune mechanisms involved in IA development.

Mathematical modelling of in-situ microaerobic desulfurization of biogas from sewage sludge digestion.

Microaeration can be used to cost-effectively remove in-situ H2S from the biogas generated in anaerobic digesters. This study is aimed at developing and validating an extension of the Anaerobic Digestion Model n°1 capable of incorporating the main phenomena which occurs during microaeration. This innovative model was implemented and tested with data from a pilot scale digester microaerated for ∼ 200 d. The results showed that despite the model's initial ability to predict the digester's behavior, its predicted performance was improved by calibrating the most influential parameters. The model's prediction potential was largely enhanced by adding retention parameters that account for the activity of sulfide oxidizing bacteria retained inside the anaerobic digester, which have been consistently shown to be responsible for a large share of the H2S removed.

Sialometaplasia Necrotizante: Revisión de la Literatura a Propósito de un Caso / Necroting Sialometaplasia: Review of the Literature on a Case

RESUMEN: La sialometaplasia necrotizante (SN) es una rara enfermedad benigna, inflamatoria, autolimitante, que afecta más frecuentemente a las glándulas salivales menores y que comúnmente se asocia a las ubicadas en la porción más posterior del paladar duro. Su etiología no esta clara, la mayoría de los autores sugieren que una lesión química, física o biológica de los vasos sanguíneos produciría cambios isquémicos, que provocarían infarto del tejido glandular con necrosis, inflamación e intento de reparación. Clínicamente puede presentarse como una úlcera de márgenes irregulares, ligeramente elevados y lecho necrótico, mientras que histopatológicamente se caracteriza por presentar metaplasia escamosa de conductos y acinos e hiperplasia pseudoepiteliomatosa del epitelio mucoso. La similitud de sus características clínicas e histopatológicas con algunas lesiones glandulares malignas de la cavidad oral, puede resultar en tratamientos innecesarios, considerando que la SN se trata de una patología autoresolutiva, por lo que es fundamental realizar un correcto diagnóstico clínico e histopatológico para evitar tratamientos quirúrgicos mutilantes o innecesarios. En el presente trabajo se presenta un caso de una mujer joven, con diagnóstico de SN, con sus características clínicas, histopatológicas y la evolución de la lesión.

ABSTRACT: The Necrotizing Sialometaplazia (NS) it's a rare self-limiting, inflammatory, benign disease, that most frequently affects the minor salivary glands and it is commonly associated to the glands located at the most posterior portion of the hard palate. Its etiology is not clear. Most authors suggest that a chemical, physical or biological lesion of the blood vessels would produce ischemic changes, which lead to infarction of muscle tissue with necrosis, inflammation and attempts to repair. Clinically it can present as a slightly elevated ulcer with irregular edges and necrotic bed, while histopathologically it is characterized for present squamous metaplasia of ducts and acini and pseudoepitheliomatous hyperplasia of mucosal epithelium. The similarity of its clinical and histopathological characteristics with some malignant glandular lesions of the oral cavity, can result in unnecessary treatments, considering that NS is a self-sustaining pathology, it is therefore essential to perform a correct clinical and histopathological diagnosis to avoid mutilating or unnecessary surgical treatments. In the present work we present the case of a young woman, with diagnosis of NS, with its clinical and histopathological characteristics and the evolution of the lesion.

Partition coefficients of methylated DNA bases obtained from free energy calculations with molecular electron density derived atomic charges.

Partition coefficients serve in various areas as pharmacology and environmental sciences to predict the hydrophobicity of different substances. Recently, they have also been used to address the accuracy of force fields for various organic compounds and specifically the methylated DNA bases. In this study, atomic charges were derived by different partitioning methods (Hirshfeld and Minimal Basis Iterative Stockholder) directly from the electron density obtained by electronic structure calculations in a vacuum, with an implicit solvation model or with explicit solvation taking the dynamics of the solute and the solvent into account. To test the ability of these charges to describe electrostatic interactions in force fields for condensed phases, the original atomic charges of the AMBER99 force field were replaced with the new atomic charges and combined with different solvent models to obtain the hydration and chloroform solvation free energies by molecular dynamics simulations. Chloroform-water partition coefficients derived from the obtained free energies were compared to experimental and previously reported values obtained with the GAFF or the AMBER-99 force field. The results show that good agreement with experimental data is obtained when the polarization of the electron density by the solvent has been taken into account, and when the energy needed to polarize the electron density of the solute has been considered in the transfer free energy. These results were further confirmed by hydration free energies of polar and aromatic amino acid side chain analogs. Comparison of the two partitioning methods, Hirshfeld-I and Minimal Basis Iterative Stockholder (MBIS), revealed some deficiencies in the Hirshfeld-I method related to the unstable isolated anionic nitrogen pro-atom used in the method. Hydration free energies and partitioning coefficients obtained with atomic charges from the MBIS partitioning method accounting for polarization by the implicit solvation model are in good agreement with the experimental values. © 2018 Wiley Periodicals, Inc.

Metástasis palpebral como primera manifestación de un tumor renal / Eyelid metastasis as first presentation of renal cell carcinoma

Caso clínico: Un varón de 87 años desarrolló en el párpado superior un nódulo de crecimiento lento, no doloroso y bien definido. El tumor de 1 cm de diámetro estaba pigmentado y adherido a planos profundos. El estudio anatomopatológico fue compatible con un carcinoma de células renales. El estudio de extensión mostró una masa tumoral en cada riñón y múltiples metástasis pulmonares. Conclusión: El oftalmólogo puede jugar un papel importante en el diagnóstico del cáncer metastásico, cuando la enfermedad ocular está presente. Por tanto, cabe destacar la relevancia de realizar una biopsia en aquellas lesiones sospechosas y/o recurrentes del párpado (AU)

Case report: An 87-year-old male presented with a slow-growing, painless and well defined nodule in the upper eyelid. The tumour measured 1cm, and was pigmented and adhered to deep planes. The histopathology analysis was compatible with renal cell carcinoma. The extension study showed a tumour mass in each kidney, as well as multiple pulmonary metastases. Discussion: The ophthalmologist can play an important role in the diagnosis of metastatic cancer when eye disease is present. Therefore, the importance of a biopsy should be noted in those suspicious and/or recurrent lesions of the eyelid (AU)

[Face protective patches do not reduce facial pressure ulcers in a simulated model of non-invasive ventilation]. / Uso de parches protectores faciales no reduce la presión facial en un modelo simulado de ventilación mecánica no invasiva.

Noninvasive ventilation (NIV) frequently involves the development of facial pressure ulcers (FPU). Its prevention considers the empirical use of protective patches between skin and mask, in order to reduce the pressure exerted by it. OBJECTIVES: To evaluate the effect of protective patches on the pressure exerted by the facial mask, and its impact on the programmed ventilatory parameters. METHOD: Bilevel NIV simulated model using full face mask in phantom with a physiological airway (ALS PRO +) in supine position. Forehead, chin and cheekbones pressure were measured using 3 types of standard protective patches versus a control group using pressure sensors (Interlinks Electronics®). The values obtained with the protective patches-mask model were evaluated in the programmed variables maximum inspiratory flow (MIF)), expired tidal volume (Vte) and positive inspiratory pressure (IPAP), with Trilogy 100 ventilator, Respironics®. The programming and recording of the variables was carried out in 8 opportunities in each group by independent operators. RESULTS: There was no decrease in facial pressure with any of the protective patches compared to the control group. Moltopren increased facial pressure at all support points (p < 0.001), increased leakage, it decreased MIF, Vte and IPAP (p < 0.001). Hydrocolloid patches increased facial pressure only in the left cheekbone, increased leakage and decreased MIF. Polyurethane patches did not produce changes in facial pressure or ventilatory variables. CONCLUSION: The use of protective patches of moltopren, hydrocolloid and polyurethane transparent did not contribute to the decrease of the facial pressure. A deleterious effect of the moltopren and hydrocolloid patches was observed on the administration of ventilatory variables, concluding that the non-use of the protective patches allowed a better administration of the programmed parameters.

Uso de parches protectores faciales no reduce la presión facial en un modelo simulado de ventilación mecánica no invasiva / Face protective patches do not reduce facial pressure ulcers in a simulated model of non-invasive ventilation

La ventilación mecánica no invasiva (VMNI) tiene como complicación frecuente el desarrollo de úlceras faciales por presión (UPP). Su prevención considera el uso empírico de parches protectores entre piel y mascarilla, para disminuir la presión ejercida por ésta. Objetivos: Evaluar el efecto de los parches protectores sobre la presión ejercida por la mascarilla facial, y su impacto en los parámetros ventilatorios programados. Método: Modelo simulado de VMNI binivelada usando mascarilla facial total en fantoma con vía aérea fisiológica (ALS PRO+) en posición supina. Se midió la presión en frente, mentón y pómulos, usando 3 tipos de parches protectores de uso habitual versus un grupo control, utilizando sensores de presión (Interlinks Electronics®). Se evaluaron los valores obtenidos con el modelo de mascarilla-parches protectores en las variables programadas flujo máximo inspiratorio (FMI), volumen corriente espirado (Vte) y presión positiva inspiratoria (IPAP), con ventilador Trilogy 100, Respironics®. La programación y registro de las variables fue efectuada en 8 oportunidades en cada grupo por operadores independientes. Resultados: No se observó disminución de la presión facial con ninguno de los parches protectores respecto al grupo control. Moltoprén aumentó la presión facial en todos los puntos de apoyo (p < 0,001), aumentó fuga, disminuyó FMI, Vte e IPAP (p < 0,001). Parches de hidrocoloide aumentaron la presión facial sólo en pómulo izquierdo, aumentaron la fuga y disminuyeron FMI. Parches de poliuretano no generaron cambios en la presión facial ni en variables ventilatorias. Conclusión: El uso de parches protectores de moltoprén, hidrocoloide y poliuretano transparente no contribuyó a la disminución de la presión facial. Se observó un efecto deletéreo de los parches de moltoprén e hidrocoloide sobre la administración de variables ventilatorias, concluyendo que el no uso de los parches protectores permitió una mejor administración de los parámetros programados.

Noninvasive ventilation (NIV) frequently involves the development of facial pressure ulcers (FPU). Its prevention considers the empirical use of protective patches between skin and mask, in order to reduce the pressure exerted by it. Objectives: To evaluate the effect of protective patches on the pressure exerted by the facial mask, and its impact on the programmed ventilatory parameters. Method: Bilevel NIV simulated model using full face mask in phantom with a physiological airway (ALS PRO +) in supine position. Forehead, chin and cheekbones pressure were measured using 3 types of standard protective patches versus a control group using pressure sensors (Interlinks Electronics®). The values obtained with the protective patches-mask model were evaluated in the programmed variables maximum inspiratory flow (MIF)), expired tidal volume (Vte) and positive inspiratory pressure (IPAP), with Trilogy 100 ventilator, Respironics®. The programming and recording of the variables was carried out in 8 opportunities in each group by independent operators. Results: There was no decrease in facial pressure with any of the protective patches compared to the control group. Moltopren increased facial pressure at all support points (p < 0.001), increased leakage, it decreased MIF, Vte and IPAP (p < 0.001). Hydrocolloid patches increased facial pressure only in the left cheekbone, increased leakage and decreased MIF. Polyurethane patches did not produce changes in facial pressure or ventilatory variables. Conclusion: The use of protective patches of moltopren, hydrocolloid and polyurethane transparent did not contribute to the decrease of the facial pressure. A deleterious effect of the moltopren and hydrocolloid patches was observed on the administration of ventilatory variables, concluding that the non-use of the protective patches allowed a better administration of the programmed parameters.

Eyelid metastasis as first presentation of renal cell carcinoma. / Metástasis palpebral como primera manifestación de un tumor renal.

CASE REPORT: An 87-year-old male presented with a slow-growing, painless and well defined nodule in the upper eyelid. The tumour measured 1cm, and was pigmented and adhered to deep planes. The histopathology analysis was compatible with renal cell carcinoma. The extension study showed a tumour mass in each kidney, as well as multiple pulmonary metastases. DISCUSSION: The ophthalmologist can play an important role in the diagnosis of metastatic cancer when eye disease is present. Therefore, the importance of a biopsy should be noted in those suspicious and/or recurrent lesions of the eyelid.

CymeR: cytometry analysis using KNIME, docker and R.

Summary: Here we present open-source software for the analysis of high-dimensional cytometry data using state of the art algorithms. Importantly, use of the software requires no programming ability, and output files can either be interrogated directly in CymeR or they can be used downstream with any other cytometric data analysis platform. Also, because we use Docker to integrate the multitude of components that form the basis of CymeR, we have additionally developed a proof-of-concept of how future open-source bioinformatic programs with graphical user interfaces could be developed. Availability and Implementation: CymeR is open-source software that ties several components into a single program that is perhaps best thought of as a self-contained data analysis operating system. Please see https://github.com/bmuchmore/CymeR/wiki for detailed installation instructions. Contact: brian.muchmore@genyo.es or marta.alarcon@genyo.es.

Osteocytic connexin hemichannels suppress breast cancer growth and bone metastasis.

Although the skeleton is one of the predominant sites for breast cancer metastasis, why breast cancer cells often become dormant after homing to bone is not well understood. Here, we reported an intrinsic self-defense mechanism of bone cells against breast cancer cells: a critical role of connexin (Cx) 43 hemichannels in osteocytes in the suppression of breast cancer bone metastasis. Cx43 hemichannels allow passage of small molecules between the intracellular and extracellular environments. The treatment of bisphosphonate drugs, either alendronate (ALN) or zoledronic acid (ZOL), opened Cx43 hemichannels in osteocytes. Conditioned media (CM) collected from MLO-Y4 osteocyte cells treated with bisphosphonates inhibited the anchorage-independent growth, migration and invasion of MDA-MB-231 human breast cancer cells and Py8119 mouse mammary carcinoma cells, and this inhibitory effect was attenuated with Cx43(E2), a specific hemichannel-blocking antibody. The opening of osteocytic Cx43 hemichannels by mechanical stimulation had similar inhibitory effects on breast cancer cells and this inhibition was attenuated by Cx43(E2) antibody as well. These inhibitory effects on cancer cells were mediated by ATP released from osteocyte Cx43 hemichannels. Furthermore, both Cx43 osteocyte-specific knockout mice and osteocyte-specific Δ130-136 transgenic mice with impaired Cx43 gap junctions and hemichannels showed significantly increased tumor growth and attenuated the inhibitory effect of ZOL. However, R76W transgenic mice with functional hemichannels but not gap junctions in osteocytes did not display a significant difference. Together, our studies establish the specific inhibitory role of osteocytic Cx43 hemichannels, and exploiting the activity of this channel could serve as a de novo therapeutic strategy.

The microphysics of collisionless shock waves.

Collisionless shocks, that is shocks mediated by electromagnetic processes, are customary in space physics and in astrophysics. They are to be found in a great variety of objects and environments: magnetospheric and heliospheric shocks, supernova remnants, pulsar winds and their nebulæ, active galactic nuclei, gamma-ray bursts and clusters of galaxies shock waves. Collisionless shock microphysics enters at different stages of shock formation, shock dynamics and particle energization and/or acceleration. It turns out that the shock phenomenon is a multi-scale non-linear problem in time and space. It is complexified by the impact due to high-energy cosmic rays in astrophysical environments. This review adresses the physics of shock formation, shock dynamics and particle acceleration based on a close examination of available multi-wavelength or in situ observations, analytical and numerical developments. A particular emphasis is made on the different instabilities triggered during the shock formation and in association with particle acceleration processes with regards to the properties of the background upstream medium. It appears that among the most important parameters the background magnetic field through the magnetization and its obliquity is the dominant one. The shock velocity that can reach relativistic speeds has also a strong impact over the development of the micro-instabilities and the fate of particle acceleration. Recent developments of laboratory shock experiments has started to bring some new insights in the physics of space plasma and astrophysical shock waves. A special section is dedicated to new laser plasma experiments probing shock physics.

The SLE variant Ala71Thr of BLK severely decreases protein abundance and binding to BANK1 through impairment of the SH3 domain function.

The B-lymphocyte kinase (BLK) gene is associated genetically with several human autoimmune diseases including systemic lupus erythematosus. We recently described that the genetic risk is given by two haplotypes: one covering several strongly linked single-nucleotide polymorphisms within the promoter of the gene that correlated with low transcript levels, and a second haplotype that includes a rare nonsynonymous variant (Ala71Thr). Here we show that this variant, located within the BLK SH3 domain, is a major determinant of protein levels. In vitro analyses show that the 71Thr isoform is hyperphosphorylated and promotes kinase activation. As a consequence, BLK is ubiquitinated, its proteasomal degradation enhanced and the average life of the protein is reduced by half. Altogether, these findings suggest that an intrinsic autoregulatory mechanism previously unappreciated in BLK is disrupted by the 71Thr substitution. Because the SH3 domain is also involved in protein interactions, we sought for differences between the two isoforms in trafficking and binding to protein partners. We found that binding of the 71Thr variant to the adaptor protein BANK1 is severely reduced. Our study provides new insights on the intrinsic regulation of BLK activation and highlights the dominant role of its SH3 domain in BANK1 binding.

[High flow nasal cannula in infants: Experience in a critical patient unit]. / Cánula nasal de alto flujo en lactantes: experiencia en una unidad de paciente crítico.

INTRODUCTION: The high flow nasal cannula (HFNC) is a method of respiratory support that is increasingly being used in paediatrics due to its results and safety. OBJECTIVE: To determine the efficacy of HFNC, as well as to evaluate the factors related to its failure and complications associated with its use in infants. PATIENTS AND METHOD: An analysis was performed on the demographic, clinical, blood gas, and radiological data, as well as the complications of patients connected to a HFNC in a critical care unit between June 2012 and September 2014. A comparison was made between the patients who failed and those who responded to HFNC. A failure was considered as the need for further respiratory support during the first 48hours of connection. The Kolmogorov Smirnov, Mann-Whitney U, chi squared and the Exact Fisher test were used, as well as correlations and a binary logistic regression model for P≤.05. RESULTS: The study included 109 patients, with a median age and weight: 1 month (0.2-20 months) and 3.7kg (2-10kg); 95 percentile: 3.7 months and 5.7kg, respectively. The most frequent diagnosis and radiological pattern was bronchiolitis (53.2%) and interstitial infiltration (56%). Around 70.6% responded. There was a significant difference between failure and response in the diagnosis (P=.013), radiography (P=018), connection context (P<.0001), pCO2 (median 40.7mmHg [15.4-67 mmHg] versus 47.3mmHg [28.6-71.3mmHg], P=.004) and hours on HFNC (median 60.75hrs [5-621.5 hrs] versus 10.5hrs [1-29 hrs], P<.0001). The OR of the PCO2 ≥ 55mmHg for failure was 2.97 (95% CI; 1.08-8.17; P=.035). No patient died and no complications were recorded. CONCLUSION: The percentage success observed was similar to that published. In this sample, the failure of HFNC was only associated with an initial pCO2 ≥ 55mmHg. On there being no complications reported as regards it use, it is considered safe, although a randomised, controlled, multicentre study is required to compare and contrast these results.