The Invasion Factor ODZ1 Is Upregulated through an Epidermal Growth Factor Receptor-Induced Pathway in Primary Glioblastoma Cells.

We have previously shown that the transmembrane protein ODZ1 promotes cytoskeletal remodeling of glioblastoma (GBM) cells and invasion of the surrounding parenchyma through the activation of a RhoA-ROCK pathway. We also described that GBM cells can control the expression of ODZ1 through transcriptional mechanisms triggered by the binding of IL-6 to its receptor and a hypoxic environment. Epidermal growth factor (EGF) plays a key role in the invasive capacity of GBM. However, the molecular mechanisms that enable tumor cells to acquire the morphological changes to migrate out from the tumor core have not been fully characterized. Here, we show that EGF is able to induce the expression of ODZ1 in primary GBM cells. We analyzed the levels of the EGF receptor (EGFR) in 20 GBM primary cell lines and found expression in 19 of them by flow cytometry. We selected two cell lines that do or do not express the EGFR and found that EGFR-expressing cells responded to the EGF ligand by increasing ODZ1 at the mRNA and protein levels. Moreover, blockade of EGF-EGFR binding by Cetuximab, inhibition of the p38 MAPK pathway, or Additionally, the siRNA-mediated knockdown of MAPK11 (p38ß MAPK) reduced the induction of ODZ1 in response to EGF. Overall, we show that EGF may activate an EGFR-mediated signaling pathway through p38ß MAPK, to upregulate the invasion factor ODZ1, which may initiate morphological changes for tumor cells to invade the surrounding parenchyma. These data identify a new candidate of the EGF-EGFR pathway for novel therapeutic approaches.

Osteomesopyknosis associated with a novel ALOX5 variant that impacts the RANKL pathway.

BACKGROUND: Bone tissue homeostasis relies on the coordinated activity of the bone-forming osteoblasts and bone-resorbing osteoclasts. Osteomesopyknosis is considered a distinctive rare sclerosing skeletal disorder of unelucidated pathophysiology and presumably autosomal dominant transmission. However, the causal genes are unknown. METHODS: We present a case report encompassing clinical assessments, imaging studies, and whole-exome sequencing analysis, complemented by functional in vitro experiments. RESULTS: This new case of osteomesopyknosis was associated with a missense ALOX5 variant predicted to induce protein misfolding and proteasomal degradation. Transfection experiments demonstrated that the variant was associated with reduced protein levels restored by proteasomal inhibition with bortezomib. Likewise, gene expression analysis showed that the mutated gene was associated with a decreased RANKL/OPG ratio, which is a critical driver of osteoclast precursor differentiation. CONCLUSION: Our data indicate impaired bone resorption as the underlying mechanism of this rare osteosclerosis, implicating ALOX5 pathogenic variants as potential etiological factors.

Analysis of COL7A1 pathogenic variants in a large cohort of dystrophic epidermolysis bullosa patients from Argentina reveals a new genotype-phenotype correlation.

Dystrophic epidermolysis bullosa (DEB) is a clinically heterogeneous heritable skin disorder, characterized by blistering of the skin and mucous membranes following minor trauma. Dominant (DDEB) and recessive (RDEB) forms are caused by pathogenic variants in COL7A1 gene. Argentina's population has a heterogeneous genetic background, and little is known about the molecular basis of DEB in our country or in native South American populations. In this study, we present the prevalence and geographical distribution of pathogenic variants found in 181 patients from 136 unrelated families (31 DDEB and 105 RDEB). We detected 95 different variants, 59 of them were previously reported in the literature and 36 were novel, nine of which were detected in more than one family. The most prevalent pathogenic variants were identified in exon 73 in DDEB patients and in exon 3 in RDEB patients. We also report a new phenotype-genotype correlation found in 10 unrelated families presenting mild blistering and severe mucosal involvement. Molecular studies in populations with an unexplored genetic background like ours revealed a diversity of pathogenic variants, and we hope that these findings will contribute to the definition of targets for new gene therapies.

Signaling Pathways Regulating the Expression of the Glioblastoma Invasion Factor TENM1.

Glioblastoma (GBM) is one of the most aggressive cancers, with dismal prognosis despite continuous efforts to improve treatment. Poor prognosis is mostly due to the invasive nature of GBM. Thus, most research has focused on studying the molecular players involved in GBM cell migration and invasion of the surrounding parenchyma, trying to identify effective therapeutic targets against this lethal cancer. Our laboratory discovered the implication of TENM1, also known as ODZ1, in GBM cell migration in vitro and in tumor invasion using different in vivo models. Moreover, we investigated the microenvironmental stimuli that promote the expression of TENM1 in GBM cells and found that macrophage-secreted IL-6 and the extracellular matrix component fibronectin upregulated TENM1 through activation of Stat3. We also described that hypoxia, a common feature of GBM tumors, was able to induce TENM1 by both an epigenetic mechanism and a HIF2α-mediated transcriptional pathway. The fact that TENM1 is a convergence point for various cancer-related signaling pathways might give us a new therapeutic opportunity for GBM treatment. Here, we briefly review the findings described so far about the mechanisms that control the expression of the GBM invasion factor TENM1.

Alteraciones cutáneas en neonatos que consultan en el departamento de urgencias pediátricas de un hospital público

RESUMEN Introducción: Los procesos dermatológicos pediátricos son problemas frecuentes a los que se enfrentan los pediatras durante la consulta Como tales debe estar familiarizados con las patologías cutáneas más comunes del recién nacido. Es de suma importancia realizar un diagnóstico correcto e instaurar una terapia adecuada para el futuro bienestar del niño que está iniciando su vida. Objetivo: Determinar la frecuencia y los tipos de alteraciones o lesiones cutáneas en neonatos que acuden al departamento de emergencias pediátricas de un hospital de referencia. Materiales y Métodos: Estudio observacional, descriptivo, prospectivo, transversal. Se evaluó neonatos que consultaron por lesiones en la piel en el Departamento de emergencias pediátricas de agosto a diciembre de 2018. Variables: Edad, sexo, procedencia, vía de nacimiento, edad gestacional, ingreso a la unidad de cuidados intensivos neonatales, tipo y extensión de las lesiones, síntomas asociados, y diagnósticos. Análisis de datos: SPSS v21 utilizando estadísticas descriptivas. Protocolo aceptado por el comité de ética institucional con consentimiento informado de los padres. Resultados: Fueron atendidos 416 neonatos, de los cuales 19,2% (N=80) consultaron por lesiones cutáneas, 32,5% (26/80) fueron pápulas, ampollas 1,3% (1/80), siendo 68,8% (55/80) localizadas. El diagnóstico de mayor frecuencia fue eritema tóxico en 21,3% (17/80). La fiebre estuvo asociada en 6,3% (5/80) a las infecciones de piel y un neonato presento sepsis bacteriana con puerta de entrada cutánea. Conclusiones: las lesiones cutáneas más frecuentes fueron las lesiones transitorias. El eritema toxico fue la alteración cutánea predominante. Las infecciones de piel se presentaron en el 25% % en neonatos

ABSTRACT Introduction: Pediatric dermatological processes are frequent problems that pediatricians face during consultation. As such, they must be familiar with the most common skin pathologies of the newborn. It is extremely important to make a correct diagnosis and establish an appropriate therapy for the future well-being of the child who is beginning his life. Objective: To determine the frequency and types of alterations or skin lesions in newborns who present to the pediatric emergency department of a reference hospital. Materials and Methods: This was an observational, descriptive, prospective and cross-sectional study. Newborns who consulted for skin lesions in the Pediatric Emergency Department from August to December 2018 were evaluated. Variables were age, sex, place of origin, route of birth, gestational age, admission to the neonatal intensive care unit, type and extension of injuries, associated symptoms, and diagnoses. Data analysis: SPSS v21 using descriptive statistics. Our protocol was accepted by the institutional ethics committee, parental informed consent was obtained. Results: 416 newborns were treated, of which 19.2% (N=80) consulted for skin lesions, 32.5% (26/80) were papules, blisters 1.3% (1/80), 68,8% (55/80) were localized findings. The most frequent diagnosis was toxic erythema in 21.3% (17/80). Fever was associated in 6.3% (5/80) with skin infections and one newborn presented with bacterial sepsis from a cutaneous entry portal. Conclusions: the most frequent skin lesions were transient lesions. Toxic erythema was the predominant cutaneous alteration. Skin infections occurred in 25% % in newborns.

HIF2α Upregulates the Migration Factor ODZ1 under Hypoxia in Glioblastoma Stem Cells.

Background: Glioblastoma (GBM) remains a major clinical challenge due to its invasive capacity, resistance to treatment, and recurrence. We have previously shown that ODZ1 contributes to glioblastoma invasion and that ODZ1 mRNA levels can be upregulated by epigenetic mechanisms in response to hypoxia. Herein, we have further studied the transcriptional regulation of ODZ1 in GBM stem cells (GSCs) under hypoxic conditions and analyzed whether HIF2α has any role in this regulation. Methods: We performed the experiments in three primary GSC cell lines established from tumor specimens. GSCs were cultured under hypoxia, treated with HIF regulators (DMOG, chetomin), or transfected with specific siRNAs, and the expression levels of ODZ1 and HIF2α were analyzed. In addition, the response of the ODZ1 promoter cloned into a luciferase reporter plasmid to the activation of HIF was also studied. Results: The upregulation of both mRNA and protein levels of HIF2α under hypoxia conditions correlated with the expression of ODZ1 mRNA. Moreover, the knockdown of HIF2α by siRNAs downregulated the expression of ODZ1. We found, in the ODZ1 promoter, a HIF consensus binding site (GCGTG) 1358 bp from the transcription start site (TSS) and a HIF-like site (CCGTG) 826 bp from the TSS. Luciferase assays revealed that the stabilization of HIF by DMOG resulted in the increased activity of the ODZ1 promoter. Conclusions: Our data indicate that the HIF2α-mediated upregulation of ODZ1 helps strengthen the transcriptional control of this migration factor under hypoxia in glioblastoma stem cells. The discovery of this novel transcriptional pathway identifies new targets to develop strategies that may avoid GBM tumor invasion and recurrence.

Glioblastoma invasion factor ODZ1 is induced by microenvironmental signals through activation of a Stat3-dependent transcriptional pathway.

We have previously shown that the transmembrane protein ODZ1 serves for glioblastoma (GBM) cells to invade the surrounding tissue through activation of RhoA/ROCK pathway. However, the transcriptional machinery used by GBM cells to regulate the expression of ODZ1 is unknown. Here we show that interaction with tumor microenvironment elements, mainly activated monocytes through IL-6 secretion, and the extracellular matrix protein fibronectin, induces the Stat3 transcriptional pathway and upregulates ODZ1 which results in GBM cell migration. This signaling route is abrogated by blocking the IL-6 receptor, inhibiting Jak kinases or knocking down Stat3. Furthermore, we have identified a Stat3 responsive element in the ODZ1 gene promoter, about 1 kb from the transcription start site. Luciferase-reporter assays confirmed that the promoter responds to the presence of monocytic cells and this activation is greatly reduced when the Stat3 site is mutated or following treatment with a neutralizing anti-IL-6 receptor antibody or transfecting GBM cells with a dominant negative variant of Stat3. Overall, we show that monocyte-secreted IL-6 and the extracellular matrix protein fibronectin activate the axis Stat3-ODZ1 and promote migration of GBM cells. This is the first described transcriptional mechanism used by tumor cells to promote the expression of the invasion factor ODZ1.

Landscape of Germline Genetic Variants in AGT, MGMT, and TP53 in Mexican Adult Patients with Astrocytoma.

Astrocytoma is the most common type of primary brain tumor. The risk factors for astrocytoma are poorly understood; however, germline genetic variants account for 25% of the risk of developing gliomas. In this study, we assessed the risk of astrocytoma associated with variants in AGT, known by its role in angiogenesis, TP53, a well-known tumor suppressor and the DNA repair gene MGMT in a Mexican population. A case-control study was performed in 49 adult Mexican patients with grade II-IV astrocytoma. Sequencing of exons and untranslated regions of AGT, MGMT, and TP53 from was carried in an Ion Torrent platform. Individuals with Mexican Ancestry from the 1000 Genomes Project were used as controls. Variants found in our cohort were then assessed in a The Cancer Genome Atlas astrocytoma pan-ethnic validation cohort. Variants rs1926723 located in AGT (OR 2.74, 1.40-5.36 95% CI), rs7896488 in MGMT (OR 3.43, 1.17-10.10 95% CI), and rs4968187 in TP53 (OR 2.48, 1.26-4.88 95% CI) were significantly associated with the risk of astrocytoma after multiple-testing correction. This is the first study where the AGT rs1926723 variant, TP53 rs4968187, and MGMT rs7896488 were found to be associated with the risk of developing an astrocytoma.

Transitory response of a myelodysplastic syndrome with deletion of chromosome 5q to thalidomide. Report of one case

ABSTRACT Myelodysplastic syndrome with deletion of chromosome 5q (5q-syndrome) has a favorable prognosis and a low risk of transformation to acute myeloid leukemia, when treated with lenalidomide. Azacitidine leads to complete remission even as second-line therapy and in patients with clonal evolution. We report a 70 years old female without previous exposure to myelotoxic drugs, presenting with three weeks with fatigue and dyspnea. She had anemia with normal white blood cell and platelet count. Bone marrow biopsy showed 50% cellularity and the karyotype analysis revealed a (5) (q33q34) deletion in 22% of the metaphases. A diagnosis of 5q-syndrome with low risk calculated using the Revised International Prognostic Scoring System (IPSS-R), was made. Since lenalidomide was not affordable, thalidomide 100 mg/day was initiated, achieving transfusion independence for three years. Afterwards, she developed pancytopenia and a bone marrow biopsy showed erythroid and megakaryocyte dysplasia with a complex karyotype, which worsened prognosis (IPSS-R of five points). Therefore, azacitidine (by donation) was administered. She achieved complete remission with a normal karyotype and completed 12 cycles of treatment. Thereafter, she relapsed and received only supportive care for a year. She suffered an ischemic stroke and died two weeks later.

El síndrome mielodisplásico con deleción del cromosoma 5q (síndrome 5q) tiene un pronóstico favorable y riesgo bajo de transformación a leucemia aguda en pacientes que son tratados con lenalidomida (tratamiento estándar). El uso Azactidina tiene respuestas completas incluso como segunda línea de tratamiento en pacientes con evolución clonal. Presentamos una mujer de 71 años, sin exposición a mielotóxicos que debutó con un síndrome anémico. Se realizó biopsia de medula ósea que mostró celularidad del 50% y en el análisis citogenético se detectó una deleción del cromosoma 5 en 22% de las metafases analizadas, lo que llevó al diagnóstico de Síndrome 5q- de riesgo bajo de acuerdo con el puntaje IPSS-R (Revised International Prognostic Scoring System). Ya que no se pudo costear lenalidomida, se trató con talidomida (100 mg/día). Permaneció tres años sin requerir soporte transfusional. Posteriormente, presentó pancitopenia y en el nuevo aspirado de médula ósea se observó displasia de la serie roja y megacariocitos, con cariotipo complejo y peor pronóstico (IPSS-R 5 puntos). Se trató con 12 ciclos de azacitidina con lo que logró respuesta completa. Recayó 12 meses después y continuó manejo de soporte por un año. Finalmente falleció debido a un accidente vascular cerebral.

Síndrome inflamatorio multisistémico en niños asociado al SARS-CoV-2

RESUMEN En general la afectación del Covid 19 en niños es leve o asintomática. Un porcentaje pequeño de pacientes requirieron ingreso a la Unidad de cuidados intensivos pediátricos. Se reporta el caso de un paciente pediátrico hospitalizado en Unidad de Cuidados Intensivos de un hospital pediátrico, en el contexto de la pandemia SARS-CoV-2, que requirió ingreso a la UCI por presentar un shock tóxico, con marcadores inflamatorios, reactantes de fase aguda elevados y manifestaciones clínicas que corresponden al Síndrome Inflamatorio Multisistémico descripto recientemente y relacionado a la infección por COVID-19.

ABSTRACT In general, Covid 19 infection in children is mild or asymptomatic. A small percentage of patients require admission to the Pediatric Intensive Care Unit. We report the case of a pediatric patient hospitalized in the Intensive Care Unit of a pediatric hospital, in the context of the SARS-CoV-2 pandemic, who required admission to the ICU due to toxic shock, with elevation of inflammatory markers and acute phase reactants, along with clinical manifestations that corresponded to the recently described Multisystemic Inflammatory Syndrome related to COVID-19 infection.

A novel pathogenic FERMT1 variant in four families with Kindler syndrome in Argentina.

BACKGROUND: Kindler syndrome is a rare genodermatosis. Major clinical criteria include acral blistering in infancy and childhood, progressive poikiloderma, skin atrophy, abnormal photosensitivity, and gingival fragility. METHODS: FERMT1 gene was sequenced in 5 patients with a clinical diagnosis of Kindler syndrome. RESULTS: We report a novel pathogenic variant detected in four unrelated families of Paraguayan origin, where one nucleotide deletion in FERMT1 gene (c.450delG) is predicted to cause a frameshift mutation leading to loss of function. Haplotype analysis revealed the propagation of an ancestral allele through this population. CONCLUSIONS: The identification of this recurrent pathogenic variant enables optimization of molecular detection strategies in our patients, reducing the cost of diagnosis.

Transitory response of a myelodysplastic syndrome with deletion of chromosome 5q to thalidomide. Report of one case.

Myelodysplastic syndrome with deletion of chromosome 5q (5q-syndrome) has a favorable prognosis and a low risk of transformation to acute myeloid leukemia, when treated with lenalidomide. Azacitidine leads to complete remission even as second-line therapy and in patients with clonal evolution. We report a 70 years old female without previous exposure to myelotoxic drugs, presenting with three weeks with fatigue and dyspnea. She had anemia with normal white blood cell and platelet count. Bone marrow biopsy showed 50% cellularity and the karyotype analysis revealed a (5) (q33q34) deletion in 22% of the metaphases. A diagnosis of 5q-syndrome with low risk calculated using the Revised International Prognostic Scoring System (IPSS-R), was made. Since lenalidomide was not affordable, thalidomide 100 mg/day was initiated, achieving transfusion independence for three years. Afterwards, she developed pancytopenia and a bone marrow biopsy showed erythroid and megakaryocyte dysplasia with a complex karyotype, which worsened prognosis (IPSS-R of five points). Therefore, azacitidine (by donation) was administered. She achieved complete remission with a normal karyotype and completed 12 cycles of treatment. Thereafter, she relapsed and received only supportive care for a year. She suffered an ischemic stroke and died two weeks later.

Hypoxia Can Induce Migration of Glioblastoma Cells Through a Methylation-Dependent Control of ODZ1 Gene Expression.

The transmembrane protein ODZ1 has been associated with the invasive capacity of glioblastoma (GBM) cells through upregulation of RhoA/ROCK signaling, but the mechanisms triggering the ODZ1 pathway remain elusive. In addition, it is widely accepted that hypoxia is one of the main biological hallmarks of the GBM microenvironment and it is associated with treatment resistance and poor prognosis. Here we show that hypoxic tumor regions express higher levels of ODZ1 and that hypoxia induces ODZ1 expression in GBM cells by regulating the methylation status of the ODZ1 promoter. Hypoxia-induced upregulation of ODZ1 correlates with higher migration capacity of GBM cells that is drastically reduced by knocking down ODZ1. In vitro methylation of the promoter decreases its transactivation activity and we found a functionally active CpG site at the 3'end of the promoter. This site is hypermethylated in somatic neural cells and mainly hypomethylated in GBM cells. Mutagenesis of this CpG site reduces the promoter activity in response to hypoxia. Overall, we identify hypoxia as the first extracellular activator of ODZ1 expression and describe that hypoxia controls the levels of this migration-inducer, at least in part, by regulating the methylation status of the ODZ1 gene promoter.

Transient monoclonal gammopathy and hypercalcemia in a male patient with Systemic Lupus Erythematosus / Gammapatía monoclonal transitoria e hipercalcemia en un paciente masculino con lupus eritematoso sistémico

Systemic Lupus Erythematosus (SLE) as an autoimmune disorder, is characterized by a profound B cell activation, however, the association of this disease with a monoclonal gammopathy has been infrequently reported, while hypercalcemia is associated with Hypercalcemia-Lymphadenopathy Syndrome (HL-SLE). We report the case of a 45-year-old man, with anemia, hypoalbuminemia, hypergammaglobulinemia, hypercalcemia, and bone marrow infiltrated with plasma cells. He was diagnosed as Monoclonal Gammopathy of Undetermined Significance (MGUS), one year later he attended with erythematous macules on both arms, at this time the electrophoresis reported a polyclonal hypergammaglobulinemia. Immunologic panel reported ANA 1:2560, mitochondrial ANA 1:80, anti-double-stranded DNA IgG 15.3 and hipocomplementemia. We confirmed SLE and treatment was initiated. In our patient we ruled out MGUS, γHCD (γ-heavy-chain disease) and hypercalcemia related to HL-SLE. To our knowledge, the findings of monoclonal gammopathy and hypercalcemia as the onset of SLE have never been reported and the role of clinical laboratory was very important in the approach to establish a definitive diagnosis

El lupus eritematoso sistémico (LES) es un padecimiento autoinmune, caracterizado por la activación de las células B. Se ha reportado ocasionalmente su asociación con la gammapatía monoclonal. Reportamos el caso de un varón de 45 años con anemia, hipoalbuminemia, hipergammaglobulinemia, hipercalcemia e infiltración de médula ósea con células plasmáticas. Se diagnosticó de gammapatía monoclonal de significado incierto. Posteriormente presentó máculas en brazos, con hipergammaglobulinemia policlonal y serología con ANA 1:2.560, ANA mitocondriales 1:80, IgG 15,3 e hipocomplementemia que establecieron el diagnóstico de LES. La presencia de hipercalcemia y gammapatía monoclonal en asociación con LES no se había reportado con anterioridad

Algunos aspectos clínicos-epidemiológicos de la enfermedad de Hansen en el municipio Yara .Granma. 2013-2017 / Some clinical-epidemiological aspects of Hansen's disease in the Yara municipality. Granma. 2013-2017

RESUMEN La lepra es una enfermedad transmisible tan antigua como el hombre mismo. Se realizó un estudio descriptivo retrospectivo, para caracterizar algunos aspectos clínicos-epidemiológicos de la lepra, en el período 2013 - 2017, Municipio Yara, Provincia, Granma. El universo estuvo constituido por 13 pacientes notificados y registrados con la enfermedad. Se confeccionó una planilla que recogió las variables clínicas-epidemiológicas: edad, sexo, y formas clínicas (Según Madrid y operacional o sanitaria), se utilizó el método estadístico de por cientos para el procesamiento de los datos. El año de mayor incidencia de la enfermedad fue 2014, el grupo etáreo 60-74 años aporto el mayor número de casos, el sexo masculino fue el más representativo, las formas clínicas según la clasificación de Madrid, predominante fue lepra lepromatosa, de acuerdo a la operacional, los multibacilares. La pesquisa activa y diagnóstico oportuno de la lepra podría disminuir la aparición de sus complicaciones y la invalidez que causa.

ABSTRACT The leprosy is a transmissible disease so ancient like the man per se. A descriptive retrospective study, in order to characterize some clinical epidemiologic aspects of the leprosy in the period, accomplished 2013 itself - 2017, Municipio Yara, Provincia, Granma. The universe was constituted for 13 patients notified and registered with the disease. A payroll that gathered the clinical epidemiologic variables was manufactured: Age, sex, and clinical forms (According To Madrid and operational or sanitary), you utilized the statistical method of by the hundreds for the processing of the data. The year of bigger incidence of the disease was 2014, the group etáreo 60-74 years I contribute the bigger number of cases, the masculine sex was the more representative, the clinical forms according to the classification of Madrid, prevailing lepromatosa, according to the operational the multi-bacillar was leprosy. The active investigation and opportune diagnosis of the leprosy would be able to decrease the appearing of his complications that it causes and the invalidity.

Algunos aspectos clínicos-epidemiológicos de la enfermedad de Hansen en el municipio Yara, Granma, 2013-2017 / Some clinical-epidemiological aspects of Hansen's disease in the Yara municipality. Granma, 2013-2017

La lepra es una enfermedad transmisible tan antigua como el hombre mismo. Se realizó un estudio descriptivo retrospectivo, para caracterizar algunos aspectos clínicos-epidemiológicos de la lepra, en el período 2013–2017, Municipio Yara, Provincia, Granma. El universo estuvo constituido por 13 pacientes notificados y registrados con la enfermedad. Se confeccionó una planilla que recogió las variables clínicas-epidemiológicas: edad, sexo, y formas clínicas (Según Madrid y operacional o sanitaria), se utilizó el método estadístico de por cientos para el procesamiento de los datos. El año de mayor incidencia de la enfermedad fue 2014, el grupo etáreo 60-74 años aporto el mayor número de casos, el sexo masculino fue el más representativo, las formas clínicas según la clasificación de Madrid, predominante fue lepra lepromatosa, de acuerdo a la operacional, los multibacilares. La pesquisa activa y diagnóstico oportuno de la lepra podría disminuir la aparición de sus complicaciones y la invalidez que causa(AU)

The leprosy is a transmissible disease so ancient like the man per se. A descriptive retrospective study, in order to characterize some clinical epidemiologic aspects of the leprosy in the period, accomplished 2013 it self–2017, Municipio Yara, Provincia, Granma. The universe was constituted for 13 patients notified and registered with the disease. A payroll that gathered the clinical epidemiologic variables was manufactured: Age, sex, and clinical forms (According To Madrid and operational or sanitary), you utilized the statistical method of by the hundreds for the processing of the data. The year of bigger incidence of the disease was 2014, the group etáreo 60-74 years I contribute the bigger number of cases, the masculine sex was the more representative, the clinical forms according to the classification of Madrid, prevailing lepromatosa, according to the operational the multi-bacillar was leprosy. The active investigation and opportune diagnosis of the leprosy would be able to decrease the appearing of his complications that it causes and the invalidity(EU)

Angiotensinogen rs5050 germline genetic variant as potential biomarker of poor prognosis in astrocytoma.

INTRODUCTION: Renin-angiotensin system (RAS) in brain cancer represents a scarcely explored field in neuro-oncology. Recently, some pre- and clinical studies have reported that RAS components play a relevant role in the development and behavior of gliomas. The angiotensinogen (AGT) rs5050 genetic variant has been identified as a crucial regulator of the transcription of AGT mRNA, which makes it a logical and promising target of research. The aim of this study was to determine the relationship between the AGT rs5050 genetic variant in blood with prognosis in astrocytoma. METHODS: A prospective pilot study was performed on forty-eight astrocytoma patients, who received the standard-of-care treatment. Blood samples were taken prior to surgery and DNA was sequenced using Ion Torrent next-generation sequencing and analyzed by Ion Reporter software. Descriptive, bivariate, multivariate, and survival analyses were performed using SPSS v21, STATA 12 and GraphPad Prism 7. RESULTS: Median follow-up was 41 months (range 1-48). Survival analysis showed a significant difference between the rs5050 genotypes (p = .05). We found lower survival rates in individuals with the GG-genotype of rs5050 AGT compared to patients with the TT- and TG-genotype (2 months vs. 11.5 months, respectively [p = .01]). In bivariate and multivariate analyses, GG-genotype was negatively associated with survival. CONCLUSIONS: In patients with astrocytoma, AGT rs5050 GG-genotype was associated with poor prognosis. We propose this germline genetic variant as a complementary biomarker, which can be detected practically and safely in blood samples or saliva.

¿Qué hacemos si un paciente diabético no ingresa? Nuevas pautas según el tiempo de estancia en urgencias / What to do if the patient with acute hyperglycemia is not to be admitted to hospital? A call for new protocols according to the emergency department stay

No disponible