A proteomic approach supports the clinical relevance of TAT-Cx43266-283 in glioblastoma.

Glioblastoma (GBM) is the most frequent and aggressive primary brain cancer. The Src inhibitor, TAT-Cx43266-283, exerts antitumor effects in in vitro and in vivo models of GBM. Because addressing the mechanism of action is essential to translate these results to a clinical setting, in this study we carried out an unbiased proteomic approach. Data-independent acquisition mass spectrometry proteomics allowed the identification of 190 proteins whose abundance was modified by TAT-Cx43266-283. Our results were consistent with the inhibition of Src as the mechanism of action of TAT-Cx43266-283 and unveiled antitumor effectors, such as p120 catenin. Changes in the abundance of several proteins suggested that TAT-Cx43266-283 may also impact the brain microenvironment. Importantly, the proteins whose abundance was reduced by TAT-Cx43266-283 correlated with an improved GBM patient survival in clinical datasets and none of the proteins whose abundance was increased by TAT-Cx43266-283 correlated with shorter survival, supporting its use in clinical trials.

Cuantificación de la carga de la enfermedad renal crónica en América Latina: una epidemia invisibilizada / Quantification of the burden of chronic kidney disease in Latin America: an invisible epidemic / Quantificação da carga da doença renal crônica na América Latina: uma epidemia invisível

[RESUMEN]. Objetivo. 1) Describir la carga de la enfermedad renal crónica en países de América Latina entre 1990 y 2019 y, 2) Estimar la correlación entre los años de vida saludables perdidos (AVISA) con el índice sociodemográfico y el índice de acceso y calidad de salud. Métodos. Análisis secundario y ecológico, basado en el Estudio de la Carga Global de Enfermedades, Lesiones y Factores de Riesgo 2019. Se reportaron las tasas estandarizadas de mortalidad, años perdidos por muertes prematuras (APMP), años de vida ajustados por discapacidad (AVAD) y AVISA por enfermedad renal crónica para 1990, 2005 y 2019. La información se desagregó por países, sexo, grupos etarios y subcausas. Resultados. Entre 1990 y 2019, la carga de la enfermedad renal crónica aumentó considerablemente en los países de América Latina, convirtiéndose en una de las principales causas de mortalidad y de AVISA. La tasa estandarizada de AVISA por enfermedad renal crónica se debió, en gran medida, al peso de las muertes prematuras más que a la discapacidad. En 2019, Nicaragua, El Salvador, México y Guatemala se destacaron por tener las tasas estandarizadas de mortalidad por enfermedad renal crónica y de AVISA más elevadas, mientras que Uruguay presentó las más bajas. Conclusiones. La enfermedad renal crónica es una epidemia invisibilizada que representa una carga excesiva, en mortalidad y AVISA, para los países de América Latina. Es indispensable aunar esfuerzos regionales para enfrentar la enfermedad, además de impulsar acciones locales que atiendan las particularidades de cada país.

[ABSTRACT]. Objective. 1) Describe the burden of chronic kidney disease in Latin American countries between 1990 and 2019; and 2) Estimate the correlation between disability-adjusted life years (DALYs) and the Sociodemogra- phic Index and the Healthcare Access and Quality Index. Methods. Secondary and ecological analysis, based on the 2019 Global Burden of Diseases, Injuries and Risk Factors Study. Standardized mortality rates, years of life lost to due to premature death (YLLs),years of healthy life lost due to disability (YLDs) and DALYs due to chronic kidney disease were reported for 1990, 2005, and 2019. Information was disaggregated by country, sex, age group, and sub-cause. Results. Between 1990 and 2019, the burden of chronic kidney disease increased considerably in Latin Ame- rican countries, becoming one of the main causes of mortality and DALYs. The standardized rate of DALYs for chronic kidney disease was largely due to the weight of premature deaths rather than disability. In 2019, Nica- ragua, El Salvador, Mexico, and Guatemala had the highest standardized mortality rates for chronic kidney disease and DALYs, while Uruguay had the lowest. Conclusions. Chronic kidney disease is an invisible epidemic that places an excessive burden in terms of mortality and DALYs on Latin American countries. It is essential to join forces to tackle the disease in the region, and promote local actions that address the particularities of each country.

[RESUMO]. Objetivo. 1) Descrever a carga da doença renal crônica nos países da América Latina entre 1990 e 2019 e 2) estimar a correlação entre os anos de vida saudável perdidos (AVISA), o índice sociodemográfico e o índice de acesso e qualidade da saúde. Métodos. Análise secundária e ecológica, baseada no estudo Carga Global de Doenças, Lesões e Fatores de Risco 2019 (GBD). Foram informadas taxas de mortalidade padronizadas, anos de vida perdidos por morte prematura (AVP) por morte prematura, anos de vida ajustados por incapacidade (AVAI) e AVISA devido a doença renal crônica de 1990, 2005 e 2019. Os dados foram desagregados por país, sexo, faixas etárias e causas subjacentes. Resultados. Entre 1990 e 2019, a carga de doença renal crônica aumentou consideravelmente nos países da América Latina, tornando-se uma das principais causas de mortalidade e de AVISA. A taxa padronizada de AVISA devido à doença renal crônica foi influenciada em grande parte pelo peso das mortes prematuras, e não da incapacidade. Em 2019, Nicarágua, El Salvador, México e Guatemala se destacaram por terem as maiores taxas padronizadas de mortalidade por doença renal crônica e AVISA, ao passo que Uruguai teve as menores taxas. Conclusões. A doença renal crônica é uma epidemia invisível, que representa uma carga excessiva em ter- mos de mortalidade e de AVISA para os países da América Latina. É essencial unir esforços na região para combater a doença, além de promover ações locais que atendam às particularidades de cada país.

[Quantification of the burden of chronic kidney disease in Latin America: an invisible epidemicQuantificação da carga da doença renal crônica na América Latina: uma epidemia invisível]. / Cuantificación de la carga de la enfermedad renal crónica en América Latina: una epidemia invisibilizada.

Objective: 1) Describe the burden of chronic kidney disease in Latin American countries between 1990 and 2019; and 2) Estimate the correlation between disability-adjusted life years (DALYs) and the Sociodemographic Index and the Healthcare Access and Quality Index. Methods: Secondary and ecological analysis, based on the 2019 Global Burden of Diseases, Injuries and Risk Factors Study. Standardized mortality rates, years of life lost to due to premature death (YLLs),years of healthy life lost due to disability (YLDs) and DALYs due to chronic kidney disease were reported for 1990, 2005, and 2019. Information was disaggregated by country, sex, age group, and sub-cause. Results: Between 1990 and 2019, the burden of chronic kidney disease increased considerably in Latin American countries, becoming one of the main causes of mortality and DALYs. The standardized rate of DALYs for chronic kidney disease was largely due to the weight of premature deaths rather than disability. In 2019, Nicaragua, El Salvador, Mexico, and Guatemala had the highest standardized mortality rates for chronic kidney disease and DALYs, while Uruguay had the lowest. Conclusions: Chronic kidney disease is an invisible epidemic that places an excessive burden in terms of mortality and DALYs on Latin American countries. It is essential to join forces to tackle the disease in the region, and promote local actions that address the particularities of each country.

Objetivo: 1) Descrever a carga da doença renal crônica nos países da América Latina entre 1990 e 2019 e 2) estimar a correlação entre os anos de vida saudável perdidos (AVISA), o índice sociodemográfico e o índice de acesso e qualidade da saúde. Métodos: Análise secundária e ecológica, baseada no estudo Carga Global de Doenças, Lesões e Fatores de Risco 2019 (GBD). Foram informadas taxas de mortalidade padronizadas, anos de vida perdidos por morte prematura (AVP) por morte prematura, anos de vida ajustados por incapacidade (AVAI) e AVISA devido a doença renal crônica de 1990, 2005 e 2019. Os dados foram desagregados por país, sexo, faixas etárias e causas subjacentes. Resultados: Entre 1990 e 2019, a carga de doença renal crônica aumentou consideravelmente nos países da América Latina, tornando-se uma das principais causas de mortalidade e de AVISA. A taxa padronizada de AVISA devido à doença renal crônica foi influenciada em grande parte pelo peso das mortes prematuras, e não da incapacidade. Em 2019, Nicarágua, El Salvador, México e Guatemala se destacaram por terem as maiores taxas padronizadas de mortalidade por doença renal crônica e AVISA, ao passo que Uruguai teve as menores taxas. Conclusões: A doença renal crônica é uma epidemia invisível, que representa uma carga excessiva em termos de mortalidade e de AVISA para os países da América Latina. É essencial unir esforços na região para combater a doença, além de promover ações locais que atendam às particularidades de cada país.

EGFR amplification and EGFRvIII predict and participate in TAT-Cx43266-283 antitumor response in preclinical glioblastoma models.

BACKGROUND: Glioblastoma (GBM) commonly displays epidermal growth factor receptor (EGFR) alterations (mainly amplification and EGFRvIII) and TAT-Cx43266-283 is a Src-inhibitory peptide with antitumor properties in preclinical GBM models. Given the link between EGFR and Src, the aim of this study was to explore the role of EGFR in the antitumor effects of TAT-Cx43266-283. METHODS: The effect of TAT-Cx43266-283, temozolomide (TMZ) and erlotinib (EGFR inhibitor) was studied in patient-derived GBM stem cells (GSCs) and murine neural stem cells (NSCs) with and without EGFR alterations, in vitro and in vivo. EGFR alterations were analyzed by Western blot (WB) and Fluorescence In Situ Hybridization (FISH) in these cells, and compared with Src activity and survival in GBM samples from TCGA. RESULTS: The effect of TAT-Cx43266-283 correlated with EGFR alterations in a set of patient-derived GSCs and was stronger than that exerted by TMZ and erlotinib. In fact, TAT-Cx43266-283 only affected NSCs with EGFR alterations, but not healthy NSCs. EGFR alterations correlated with Src activity and poor survival in GBM patients. Finally, tumors generated from NSCs with EGFR alterations, showed a decrease in growth, invasiveness and vascularization after treatment with TAT-Cx43266-283, which enhanced the survival of immunocompetent mice. CONCLUSION: Clinically relevant EGFR alterations are predictors of TAT-Cx43266-283 response and part of its mechanism of action, even in TMZ- and erlotinib-resistant GSCs. TAT-Cx43266-283 targets NSCs with GBM-driver mutations, including EGFR alterations, in an immunocompetent GBM model in vivo, suggesting a promising effect on GBM recurrence. Together, this study represents an important step towards the clinical application of TAT-Cx43266-283.

Cuantificación de la carga de la enfermedad renal crónica en América Latina: una epidemia invisibilizada / Quantification of the burden of chronic kidney disease in Latin America: an invisible epidemic / Quantificação da carga da doença renal crônica na América Latina: uma epidemia invisível

RESUMEN Objetivo. 1) Describir la carga de la enfermedad renal crónica en países de América Latina entre 1990 y 2019 y, 2) estimar la correlación entre los años de vida saludables perdidos (AVISA) con el índice sociodemográfico y el índice de acceso y calidad de salud. Métodos. Análisis secundario y ecológico, basado en el Estudio de la Carga Global de Enfermedades, Lesiones y Factores de Riesgo 2019. Se reportaron las tasas estandarizadas de mortalidad, años perdidos por muertes prematuras (APMP), años de vida ajustados por discapacidad (AVAD) y AVISA por enfermedad renal crónica para 1990, 2005 y 2019. La información se desagregó por países, sexo, grupos etarios y subcausas. Resultados. Entre 1990 y 2019, la carga de la enfermedad renal crónica aumentó considerablemente en los países de América Latina, convirtiéndose en una de las principales causas de mortalidad y de AVISA. La tasa estandarizada de AVISA por enfermedad renal crónica se debió, en gran medida, al peso de las muertes prematuras más que a la discapacidad. En 2019, Nicaragua, El Salvador, México y Guatemala se destacaron por tener las tasas estandarizadas de mortalidad por enfermedad renal crónica y de AVISA más elevadas, mientras que Uruguay presentó las más bajas. Conclusiones. La enfermedad renal crónica es una epidemia invisibilizada que representa una carga excesiva, en mortalidad y AVISA, para los países de América Latina. Es indispensable aunar esfuerzos regionales para enfrentar la enfermedad, además de impulsar acciones locales que atiendan las particularidades de cada país.

ABSTRACT Objective. 1) Describe the burden of chronic kidney disease in Latin American countries between 1990 and 2019; and 2) Estimate the correlation between disability-adjusted life years (DALYs) and the Sociodemographic Index and the Healthcare Access and Quality Index. Methods. Secondary and ecological analysis, based on the 2019 Global Burden of Diseases, Injuries and Risk Factors Study. Standardized mortality rates, years of life lost to due to premature death (YLLs),years of healthy life lost due to disability (YLDs) and DALYs due to chronic kidney disease were reported for 1990, 2005, and 2019. Information was disaggregated by country, sex, age group, and sub-cause. Results. Between 1990 and 2019, the burden of chronic kidney disease increased considerably in Latin American countries, becoming one of the main causes of mortality and DALYs. The standardized rate of DALYs for chronic kidney disease was largely due to the weight of premature deaths rather than disability. In 2019, Nicaragua, El Salvador, Mexico, and Guatemala had the highest standardized mortality rates for chronic kidney disease and DALYs, while Uruguay had the lowest. Conclusions. Chronic kidney disease is an invisible epidemic that places an excessive burden in terms of mortality and DALYs on Latin American countries. It is essential to join forces to tackle the disease in the region, and promote local actions that address the particularities of each country.

RESUMO Objetivo. 1) Descrever a carga da doença renal crônica nos países da América Latina entre 1990 e 2019 e 2) estimar a correlação entre os anos de vida saudável perdidos (AVISA), o índice sociodemográfico e o índice de acesso e qualidade da saúde. Métodos. Análise secundária e ecológica, baseada no estudo Carga Global de Doenças, Lesões e Fatores de Risco 2019 (GBD). Foram informadas taxas de mortalidade padronizadas, anos de vida perdidos por morte prematura (AVP) por morte prematura, anos de vida ajustados por incapacidade (AVAI) e AVISA devido a doença renal crônica de 1990, 2005 e 2019. Os dados foram desagregados por país, sexo, faixas etárias e causas subjacentes. Resultados. Entre 1990 e 2019, a carga de doença renal crônica aumentou consideravelmente nos países da América Latina, tornando-se uma das principais causas de mortalidade e de AVISA. A taxa padronizada de AVISA devido à doença renal crônica foi influenciada em grande parte pelo peso das mortes prematuras, e não da incapacidade. Em 2019, Nicarágua, El Salvador, México e Guatemala se destacaram por terem as maiores taxas padronizadas de mortalidade por doença renal crônica e AVISA, ao passo que Uruguai teve as menores taxas. Conclusões. A doença renal crônica é uma epidemia invisível, que representa uma carga excessiva em termos de mortalidade e de AVISA para os países da América Latina. É essencial unir esforços na região para combater a doença, além de promover ações locais que atendam às particularidades de cada país.

YKL-40 serum levels are predicted by inflammatory state, age and diagnosis of idiopathic inflammatory myopathies.

YKL-40 increase according to the aging process, and its functions have been associated with tissue remodeling and systemic inflammation. In Rheumatoid Arthritis (RA) it has been proposed as a possible biomarker of activity and severity, however; in the field of idiopathic inflammatory myopathies (IIM) the role of YKL-40 in IIM is not clear. Thus, we aimed to evaluate if there is an association between the serum levels and muscle tissue expression of YKL-40 with age, IIM phenotype, muscle strength and myositis disease activity. The main finding was that age is the most important variable that affects the YKL-40 serum levels. In muscle biopsy, we observed that YKL-40 is mainly expressed in infiltrating lymphoid cells than in muscle tissue. Using ANCOVA according to the b-coefficients, YKL-40 serum levels are predicted by inflammatory state, age, and IIM diagnosis.

Production and Partial Characterization of Bioactive Compounds from Underutilized Marine Bioresources for a Cosmetic Formulation: Cytotoxicity and Bioactivity Evaluation.

Hydrolyzed collagen, glycogen, and hyaluronic acid, obtained through the biotechnological valorization of underutilized marine bioresources, fulfill cosmetic industry requirements for sustainable products produced under circular economy principles. Hydrolyzed collagen was obtained by hydrolyzing blue shark collagen with papain and ultrafiltration. Glycogen was isolated from industrial mussel cooking wastewaters through ultrafiltration, precipitation, and selective polysaccharide separation. Hyaluronic acid was produced by fermentation, purification, and depolymerization. The main objective was to test the feasibility of including these three biomolecules in a cosmetic formulation as bioactive compounds. For this, the in vitro irritant potential of the three ingredients and also that of the cosmetic formulation was assayed according to the Reconstituted Human Epithelium Test method OECD 439. Moreover, an in vitro assessment of the effect of hydrolyzed collagen and hyaluronic acid combinations on mRNA expression and collagen type I synthesis was evaluated in adult human fibroblasts. This study establishes, for the first time, the potential use of particular hydrolyzed collagen and hyaluronic acid combinations as stimulators of collagen I synthesis in fibroblast cultures. Besides, it provide safety information regarding potential use of those biomolecules in the formulation of a cosmetic preparation positively concluding that both, ingredients and cosmetic preparation, resulted not irritant for skin following an international validated reference method.

Procesos de estigmatización social y accesibilidad al sistema de salud de personas con consumos problemáticos / Processes of social stigmatization and accessibility to the health system of people with problematic consumption

RESUMEN INTRODUCCIÓN: El presente trabajo es un recorte seleccionado del proyecto de investigación desarrollado en el marco de la tesis doctoral de la autora. Su objetivo fue analizar los problemas de accesibilidad al sistema de salud de personas con consumos problemáticos. MÉTODOS: La estrategia metodológica utilizada adhirió a las dimensiones básicas de la investigación en políticas, sistemas y servicios de salud: abordaje de distintos niveles de análisis y articulación entre academia y servicios de salud. Se realizaron entrevistas en profundidad a profesionales del sector y a personas con consumos problemáticos en tratamiento en la ciudad de Buenos Aires. RESULTADOS: Lo más significativo del relato de los usuarios fue la profundización del sufrimiento vivenciado por efecto de los procesos de estigmatización social. Los discursos de los profesionales mostraron consenso en la idea de que el sistema de salud suele rechazar la atención de personas con consumos problemáticos. DISCUSIÓN: El problema central no tiene relación específica con las sustancias consumidas, sino con la accesibilidad a los servicios de salud y múltiples derechos que suelen ser vulnerados en las personas afectadas. Es necesario transformar estos puntos relevantes para asegurar un marco de políticas respetuosas de los derechos humanos.

ABSTRACT INTRODUCTION: The work presented here is a selected excerpt from the research project developed within the framework of the author's doctoral thesis. Its objective was to analyze the problems of accessibility to the health system for people with problematic consumption. METHODS: The methodological strategy followed the basic dimensions of research in health policies, systems and services: approach to different levels of analysis and articulation between academia and health services. In-depth interviews were conducted with health professionals and people with problematic consumption under treatment in the city of Buenos Aires. RESULTS: The most significant finding of the users' report was the intensification of the suffering experienced as a result of the processes of social stigmatization. The speeches of the professionals showed consensus about the idea that the health care system usually rejects people with problematic consumption. DISCUSSION: The main problem is not specifically related to the substances consumed, but to the accessibility to health services and multiple rights that are usually violated to the detriment of people with these problems. It is necessary to tackle these relevant issues to ensure a policy framework that respects human rights.

Clinical and Demographic Features of Paracoccidioidomycosis in Argentina: A Multicenter Study Analysis of 466 Cases.

Information on paracoccidioidomycosis (PCM) in Argentina is fragmented and has historically been based on estimates, supported only by a series of a few reported cases. Considering the lack of global information, a national multicentric study in order to carry out a more comprehensive analysis was warranted. We present a data analysis including demographic and clinical aspects of a historical series of 466 cases recorded over 10 years (2012-2021). Patients were aged from 1 to 89 years. The general male: female (M:F) ratio was 9.5:1 with significant variation according to the age group. Interestingly, the age range 21-30 shows an M:F ratio of 2:1. Most of the cases (86%) were registered in northeast Argentina (NEA), showing hyperendemic areas in Chaco province with more than 2 cases per 10,000 inhabitants. The chronic clinical form occurred in 85.6% of cases and the acute/subacute form occurred in 14.4% of cases, but most of these juvenile type cases occurred in northwestern Argentina (NWA). In NEA, the incidence of the chronic form was 90.6%; in NWA, the acute/subacute form exceeded 37%. Diagnosis by microscopy showed 96% positivity but antibody detection displays 17% of false negatives. Tuberculosis was the most frequent comorbidity, but a diverse spectrum of bacterial, fungal, viral, parasitic, and other non-infectious comorbidities was recorded. This national multicenter registry was launched in order to better understand the current status of PCM in Argentina and shows the two endemic zones with a highly diverse epidemiology.

Impaired muscle strength is associated with ultrastructure damage in myositis.

The muscle fiber ultrastructure in Idiopathic Inflammatory Myopathies (IIM) has been scarcely explored, especially in Inclusion Body Myositis. The aim of this study was to implement the Scanning Electron Microscopy (SEM) in a small cohort of IIM patients, together with the characterization of immunological profile for a better understanding of the pathophysiology. For immunological profile characterization, we identified the presence of autoantibodies (Ro-52, OJ, EJ, PL7, PL12, SRP, Jo-1, PMScl75, PMScl100, Ku, SAE1, NXP2, MDA5, TIF1γ, Mi-2α, Mi-2ß) and quantified cytokines (IL-1ß, IFN-α2, IFN-γ, TNF-α, IL-6, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33) and chemokines (CCL2, CXCL8). The histological analysis was made by hematoxylin-eosin staining while the muscle fiber ultrastructure was characterized by SEM. We observed changes in the morphology and structure of the muscle fiber according to muscle strength and muscle enzymes. We were able to find and describe muscle fiber ultrastructure with marked irregularities, porosities, disruption in the linearity and integrity of the fascicle, more evident in patients with increased serum levels of muscle enzymes and diminished muscle strength. Despite the scarce reports about the use of SEM as a tool in all clinical phenotypes of IIM, our work provides an excellent opportunity to discuss and reframe the clinical usefulness of SEM in the diagnostic approach of IIM.

Autoantibodies in the pathogenesis of idiopathic inflammatory myopathies: Does the endoplasmic reticulum stress response have a role?

Idiopathic inflammatory myopathies (IIMs) are a group of rare, acquired autoimmune diseases characterized by profound muscle weakness and immune cell invasion into non-necrotic muscle. They are related to the presence of antibodies known as myositis-specific antibodies and myositis-associated antibodies, which are associated with various IIM phenotypes and the clinical prognosis. The possibility of the participation of other pathological mechanisms involved in the inflammatory response in IIM has been proposed. Such mechanisms include the overexpression of major histocompatibility complex class I in myofibers, which correlates with the activation of stress responses of the endoplasmic reticulum (ER). Taking into account the importance of the ER for the maintenance of homeostasis of the musculoskeletal system in the regulation of proteins, there is probably a relationship between immunological and non-immunological processes and autoimmunity, and an example of this might be IIM. We propose that ER stress and its relief mechanisms could be related to inflammatory mechanisms triggering a humoral response in IIM, suggesting that ER stress might be related to the triggering of IIMs and their auto-antibodies' production.

Group-Wise Cortical Surface Parcellation Based on Inter-Subject Fiber Clustering.

We present an automatic algorithm for the group-wise parcellation of the cortical surface. The method is based on the structural connectivity obtained from representative brain fiber clusters, calculated via an inter-subject clustering scheme. Preliminary regions were defined from cluster-cortical mesh intersection points. The final parcellation was obtained using parcel probability maps to model and integrate the connectivity information of all subjects, and graphs to represent the overlap between parcels. Two inter-subject clustering schemes were tested, generating a total of 171 and 109 parcels, respectively. The resulting parcels were quantitatively compared with three state-of-the-art atlases. The best parcellation returned 69 parcels with a Dice similarity coefficient greater than 0.5. To the best of our knowledge, this is the first diffusion-based cortex parcellation method based on whole-brain inter-subject fiber clustering.

Primeras experiencias de niños helitransportados en Uruguay / First experiences of helicopter transportation of children in Uruguay / Primeiras experiências de crianças transportadas de helicóptero no Uruguai

Se presentan los primeros tres pacientes pediátricos helitransportados con traumatismo encéfalo craneano (TEC) grave asistidos en nuestra institución. Se muestra el protocolo de asistencia utilizado en el hospital para la recepción, estabilización y oportuno traslado previa coordinación con sectores públicos y privados de asistencia médica. Se solicita consentimiento informado a los padres para el uso de los datos en actividades científicas y publicaciones.

We present the first three pediatric patients transported by helicopter with severe cranioencephalic trauma assisted at our institution. The assistance protocol used in our Hospital for the reception, stabilization and timely transfer is shown after coordination with public and private health providers. Informed consent was requested from the children's parents for the use of the data in scientific activities and publications.

Apresentamos os três primeiros pacientes pediátricos transportados de helicóptero com traumatismo cranioencefálico grave (TCE) atendidos em nossa instituição. Descrevemos o protocolo de atendimento utilizado em nosso Hospital para o acolhimento, estabilização e transferência oportuna prévia coordenação aos setores público e privado de assistência médica. Solicitamos consentimento informado aos pais para o uso dos dados em atividades e publicações científicas.

Fiber Clustering Acceleration With a Modified Kmeans++ Algorithm Using Data Parallelism.

Fiber clustering methods are typically used in brain research to study the organization of white matter bundles from large diffusion MRI tractography datasets. These methods enable exploratory bundle inspection using visualization and other methods that require identifying brain white matter structures in individuals or a population. Some applications, such as real-time visualization and inter-subject clustering, need fast and high-quality intra-subject clustering algorithms. This work proposes a parallel algorithm using a General Purpose Graphics Processing Unit (GPGPU) for fiber clustering based on the FFClust algorithm. The proposed GPGPU implementation exploits data parallelism using both multicore and GPU fine-grained parallelism present in commodity architectures, including current laptops and desktop computers. Our approach implements all FFClust steps in parallel, improving execution times in all of them. In addition, our parallel approach includes a parallel Kmeans++ algorithm implementation and defines a new variant of Kmeans++ to reduce the impact of choosing outliers as initial centroids. The results show that our approach provides clustering quality results very similar to FFClust, and it requires an execution time of 3.5 s for processing about a million fibers, achieving a speedup of 11.5 times compared to FFClust.

Geographical Latitude Remains as an Important Factor for the Prevalence of Some Myositis Autoantibodies: A Systematic Review.

The idiopathic inflammatory myopathies (IIM) are characterized by muscular weakness, cutaneous manifestations, muscle damage revealed by increase of muscular enzymes, muscle biopsy, electromyography and changes on magnetic resonance imaging. However, the hallmark of these IIM, is the development of myositis specific antibodies (MSA) or myositis associated antibodies (MAA). The theories about their presence in the serum of IIM is not known. Some studies have suggested that some of these MSA, such as anti-Mi-2 increases according to the intensity of UV radiation. There is scarce information about the environmental factors that might contribute in order to be considered as triggering factors as UV radiation might be. In this review, we analyzed the reported prevalence of MSAs and MAAs regarding to their geographical location and the possible relation with UV radiation. We collected the prevalence data of fifteen MSA and thirteen MAA from 22 countries around the world and we were able to observe a difference in prevalence between countries and continents. We found differences in anti-PL7, anti-Ro52, anti-La and anti-Ku prevalence according to UV radiation level. Otherwise, we observed that anti-Mi-2 prevalence increases near to the Equator meanwhile anti-MJ/NXP2 and anti-ARS prevalence had an opposite behavior increasing their prevalence in the geographical locations farther to the Equator. Our results highlighted the importance to include the UV radiation and other environmental factors in IIM studies, in order to clarify its association with MSA and MAA prevalence as well as its possible role in the immunopathogenesis of these diseases.

Assessment of Occupational Health and Job Satisfaction in Workers with Intellectual Disability: A Job Demands-Resources Perspective.

In the contexts where people with intellectual disability work, there are factors that determine their job satisfaction. The objective of this study was to test the adequacy of the central assumptions of the Job Demands-Resources (JD-R) theory in workers with intellectual disability employed in different work alternatives. Data from 362 workers in sheltered workshops and 192 workers in supported employment were utilized. The model was contrasted using a structural equation model and a multi-group analysis. The results supported the suitability of the model and confirmed that job demands and job resources evoke two relatively independent processes such as health impairment and motivational process. The multi-group analysis confirmed the invariance of the model between the two work alternatives. Thus, the JD-R model offers a useful framework to explain the job satisfaction of workers with intellectual disability. Implications for the improvement of personal and job results are discussed.

Going Further: Comprehensive Disease Control of Rheumatoid Arthritis, Targeting Cytokines and Chemokines.

OBJECTIVES: Mechanism of action of biological and synthetic disease-modifying antirheumatic drugs (DMARDs) includes the inhibition of specific proinflammatory cytokines. This study aimed to elucidate the cytokines and chemokines inhibited by different treatments (conventional synthetic DMARD [csDMARD], biological and targeted synthetic DMARD) in rheumatoid arthritis (RA). METHODS: Fifty-nine RA patients with low disease activity or remission included in a cross-sectional study were classified by treatment in groups: abatacept, certolizumab, rituximab (RTX), tocilizumab, tofacitinib (TOF), baricitinib (BAR), and csDMARD. Cytokine and chemokine serum levels were measured by LEGENDplex Human Inflammation panel. Quantitative variables were compared using Student t or Mann-Whitney U test as appropriate, whereas qualitative variables were compared using χ2 or Fisher exact test. p < 0.05 was considered significant. RESULTS: Certolizumab, RTX, tocilizumab, and TOF showed that most cytokine pathways inhibited: tumor necrosis factor α, interferon γ, interleukin 1ß (IL-1ß), IL-12, IL-18, and IL-23; in addition, csDMARDs showed a similar inhibition patron except for IL-23. Serum level of tumor necrosis factor α pathway was one of the most inhibited being undetectable in RTX, TOF, and BAR groups. Interleukin 6 was shown to be inhibited by abatacept, RTX, and TOF; however, higher levels were observed in 3 patients treated with tocilizumab. Abatacept, certolizumab, RTX, and TOF downregulated IL-10 in this group of patients but remained detectable in almost half of the subjects, with the highest levels in the BAR group. The active pathways that remained the most were CC chemokine ligand 2, IL-8, IL-17, and IL-33. CONCLUSIONS: Understanding the cytokine chemokine pathways inhibition could help rheumatologists to prescribe a tailored therapy using the arsenal of DMARDs for individualized RA treatment in an evidence-based decision manner.

Targeting metabolic plasticity in glioma stem cells in vitro and in vivo through specific inhibition of c-Src by TAT-Cx43266-283.

BACKGROUND: Glioblastoma is the most aggressive primary brain tumour and has a very poor prognosis. Inhibition of c-Src activity in glioblastoma stem cells (GSCs, responsible for glioblastoma lethality) and primary glioblastoma cells by the peptide TAT-Cx43266-283 reduces tumorigenicity, and boosts survival in preclinical models. Because c-Src can modulate cell metabolism and several reports revealed poor clinical efficacy of various antitumoral drugs due to metabolic rewiring in cancer cells, here we explored the inhibition of advantageous GSC metabolic plasticity by the c-Src inhibitor TAT-Cx43266-283. METHODS: Metabolic impairment induced by the c-Src inhibitor TAT-Cx43266-283 in vitro was assessed by fluorometry, western blotting, immunofluorescence, qPCR, enzyme activity assays, electron microscopy, Seahorse analysis, time-lapse imaging, siRNA, and MTT assays. Protein expression in tumours from a xenograft orthotopic glioblastoma mouse model was evaluated by immunofluorescence. FINDINGS: TAT-Cx43266-283 decreased glucose uptake in human GSCs and reduced oxidative phosphorylation without a compensatory increase in glycolysis, with no effect on brain cell metabolism, including rat neurons, human and rat astrocytes, and human neural stem cells. TAT-Cx43266-283 impaired metabolic plasticity, reducing GSC growth and survival under different nutrient environments. Finally, GSCs intracranially implanted with TAT-Cx43266-283 showed decreased levels of important metabolic targets for cancer therapy, such as hexokinase-2 and GLUT-3. INTERPRETATION: The reduced ability of TAT-Cx43266-283-treated GSCs to survive in metabolically challenging settings, such as those with restricted nutrient availability or the ever-changing in vivo environment, allows us to conclude that the advantageous metabolic plasticity of GSCs can be therapeutically exploited through the specific and cell-selective inhibition of c-Src by TAT-Cx43266-283. FUNDING: Spanish Ministerio de Economía y Competitividad (FEDER BFU2015-70040-R and FEDER RTI2018-099873-B-I00), Fundación Ramón Areces. Fellowships from the Junta de Castilla y León, European Social Fund, Ministerio de Ciencia and Asociación Española Contra el Cáncer (AECC).