Synthesis of Cytotoxic Benzofurans and Ethers Derivatives of Paeonol.

Paeonol is a broadly studied natural product due to its many biological activities. Using a methodology previously employed by our research group, 11 derivatives of paeonol were synthesized (seven of them are unpublished compounds), including four ethers and seven benzofurans. Additionally, we determined the crystal structure of one of these ether derivatives (1 a) and of five benzofuran derivatives (2 a, 2 b, 2 c, 2 f and 2 g) by single crystal X-ray diffraction. To continue studying the cytotoxicity of this natural product and its derivatives, all compounds were tested against two cancer cell lines, HCT116 and MCF-7. Compounds 2 b, 2 e, and 2 g were considered active against the colorectal adenocarcinoma cells HCT116 (Growth inhibition >60 %). Compound 2 e showed an IC50 of 0.2 µM and was selected for further analysis, results reinforce its anticancer potential.

Actualización en la detección de la tuberculosis a través de pruebas moleculares / An update on the detection of tuberculosis through molecular testing

La tuberculosis es una enfermedad infecciosa respiratoria que afecta a un tercio de la población mundial y es una amenaza significativa para la salud global. La detección de la tuberculosis de manera temprana es crucial para un tratamiento eficaz y prevenir su propagación. Una solución para mejorar el diagnóstico y abordar la resistencia a los medicamentos antituberculosos es el uso de pruebas moleculares de alto rendimiento para la identificación del Mycobacterium tuberculosis y su susceptibilidad. Este estudio de revisión narrativa busca describir las generalidades, la eficacia, la sensibilidad, las ventajas y las limitaciones de las principales pruebas moleculares; Truenat® MTB, MTB plus y MTB-RIF, Abbott RealTime MTB y MTB RIF/INH en el sistema m2000sp y m2000rt y FluoroType MTBDR, además, de compararlas con GeneXpert MTB/RIF o Xpert Ultra, utilizadas para la detección del patógeno resistente a medicamentos tuberculosos. Estas pruebas utilizan diversas técnicas para la detección del ADN del Mycobacterium tuberculosis y la cuantificación de la carga bacteriana con alta sensibilidad y especificidad, resultados rápidos, reducción de los errores humanos, así como la detección temprana de cepas drogo-resistentes. A pesar de que requieren infraestructura especializada y competencias profesionales para su implementación, representan avances significativos con el potencial de mejorar la atención sanitaria y la gestión de la tuberculosis. Estas pruebas moleculares, comparadas con el GeneXpert, son una alternativa viable, aunque esta última tecnología sigue siendo la preferida en áreas con recursos limitados

Tuberculosis is a respiratory infectious disease that affects one third of the world's population and is a significant threat to global health. Detecting tuberculosis early is crucial for effective treatment and preventing its spread. One solution to improve diagnosis and address antituberculosis drug resistance is the use of high-throughput molecular tests for the identification of Mycobacterium tuberculosis and its susceptibility. This narrative review study seeks to describe the generalities, efficacy, sensitivity, advantages and limitations of the main molecular tests: Truenat® MTB, MTB plus and MTB-RIF, Abbott RealTime MTB and MTB RIF/INH on the m2000sp and m2000rt system and FluoroType MTBDR, and to compare them with GeneXpert MTB/RIF or Xpert Ultra, used for the detection of the tuberculosis drug-resistant pathogen. These tests use various techniques for the detection of Mycobacterium tuberculosis DNA and quantification of bacterial load with high sensitivity and specificity, rapid results, reduction of human error, as well as early detection of drug-resistant strains

Encuesta sobre usos y prácticas de Doppler transcraneal en pacientes neurocríticos en unidades de cuidados intensivos pediátricos de Argentina / Survey on the use and practice of transcranial Doppler ultrasound in neurocritical patients in pediatric intensive care Units in Argentina

Introducción. El uso del Doppler transcraneal (DTC) en pacientes neurocríticos se reporta cada vez más en las terapias intensivas pediátricas. El objetivo de esta encuesta es conocer los usos y prácticas del DTC en la atención neurocrítica y el proceso de formación del personal que realiza el estudio. Materiales y métodos. Encuesta a profesionales de 23 unidades de terapia intensiva pediátrica de Argentina. Resultados. Porcentaje de respuesta del 86 %. Se utilizó en sospecha de muerte encefálica (n = 20), trauma de cráneo (n = 16) y accidente cerebrovascular (n = 16). El intensivista pediátrico es quien realiza los estudios (n = 13/20). Los encuestados utilizan el Doppler para decidir conductas y tratamientos, comenzar el proceso de evaluación de muerte encefálica, solicitar tomografía de cerebro y manejar la presión de perfusión cerebral con vasopresores. Conclusión. Todos los encuestados utilizan los hallazgos del DTC para guiar tratamientos o conductas. La mitad de los encuestados está poco conforme con la capacitación recibida.

Introduction. The use of transcranial Doppler (TCD) ultrasoundin neurocritical patients is reported to be increasingly common in pediatric intensive care units. The objective of this survey was to know about the use and practice of TCD ultrasound in neurocritical care and the training process of staff members performing it. Materials and methods. Survey administered to providers from 23 pediatric intensive care units of Argentina. Results. The percentage of response was 86%. TCD ultrasound was used for suspected brain death (n = 20), head injury (n = 16), and stroke (n = 16). Pediatric intensivists perform the test (n = 13/20). Surveyed participants use TCD ultrasound to decide on treatment and management, start brain death assessment, request brain computed tomography, and manage cerebral perfusion pressure with vasopressors. Conclusion. All surveyed participants use TCD ultrasound findings to guide management or treatments. Half of surveyed participants are little satisfied with their training.

Survey on the use and practice of transcranial Doppler ultrasound in neurocritical patients in pediatric intensive care Units in Argentina. / Encuesta sobre usos y prácticas de Doppler transcraneal en pacientes neurocríticos en unidades de cuidados intensivos pediátricos de Argentina.

INTRODUCTION: The use of transcranial Doppler (TCD) ultrasound in neurocritical patients is reported to be increasingly common in pediatric intensive care units. The objective of this survey was to know about the use and practice of TCD ultrasound in neurocritical care and the training process of staff members performing it. MATERIAL AND METHODS: Survey administered to providers from 23 pediatric intensive care units of Argentina. RESULTS: The percentage of response was 86%. TCD ultrasound was used for suspected brain death (n = 20), head injury (n = 16), and stroke (n = 16). Pediatric intensivists perform the test (n = 13/20). Surveyed participants use TCD ultrasound to decide on treatment and management, start brain death assessment, request brain computed tomography, and manage cerebral perfusion pressure with vasopressors. CONCLUSIONS: All surveyed participants use TCD ultrasound findings to guide management or treatments. Half of surveyed participants are little satisfied with their training.

Introducción. El uso del Doppler transcraneal (DTC) en pacientes neurocríticos se reporta cada vez más en las terapias intensivas pediátricas. El objetivo de esta encuesta es conocer los usos y prácticas del DTC en la atención neurocrítica y el proceso de formación del personal que realiza el estudio. Materiales y métodos. Encuesta a profesionales de 23 unidades de terapia intensiva pediátrica de Argentina. Resultados. Porcentaje de respuesta del 86 %. Se utilizó en sospecha de muerte encefálica (n = 20), trauma de cráneo (n = 16) y accidente cerebrovascular (n = 16). El intensivista pediátrico es quien realiza los estudios (n = 13/20). Los encuestados utilizan el Doppler para decidir conductas y tratamientos, comenzar el proceso de evaluación de muerte encefálica, solicitar tomografía de cerebro y manejar la presión de perfusión cerebral con vasopresores. Conclusión. Todos los encuestados utilizan los hallazgos del DTC para guiar tratamientos o conductas. La mitad de los encuestados está poco conforme con la capacitación recibida.

Autoimmune manifestations in pediatric patients with human type I T - cell lymphotropic virus (HTLV-1) infection / Manifestaciones autoinmunes en pacientes pediátricos con infección por virus linfotrópico humano de células T tipo I (HTLV-1)

ABSTRACT HTLV-1 is a retrovirus that has an impact on human health due to its T-lymphocyte tropism. It occurs worldwide, but is more prevalent in tropical regions. Although most infected individuals will remain asymptomatic, the infection may manifest with complications such as uveitis, myelopathy, and leukemia, among others. The diagnosis is a chieved by the detection of anti-HTLV antibodies and a confirmatory test (Western Blot or proviral load). Although there is no specific treatment, medical treatments are aimed towards the management of secondary diseases. Three cases are described of pediatric patients diagnosed with HTLV-1 infection and associated autoimmune manifestations.

RESUMEN El virus linfotrópico humano de células T tipo I (HTLV-1) es un retrovirus que causa impacto en la salud del ser humano debido al tropismo para infectar a linfocitos T. Está distribuido mundialmente, pero es más prevalente en regiones tropicales. La mayoría de las personas afectadas permanecen asintomáticas, sin embargo, al manifestarse puede causar complicaciones como uveítis, mielopatía y leucemia, entre otras. Su diagnóstico se hace mediante la determinación de anticuerpos anti-HTLV y prueba confirmatoria (Western Blot o carga proviral). No tiene tratamiento específico, las medidas están dirigidas a la prevención y el manejo de las afecciones secundarias. Se describen tres pacientes en edad pediátrica con diagnóstico de infección por HTLV-1 y manifestaciones autoinmunes.

Early Genomic, Epidemiological, and Clinical Description of the SARS-CoV-2 Omicron Variant in Mexico City.

Omicron is the most mutated SARS-CoV-2 variant-a factor that can affect transmissibility, disease severity, and immune evasiveness. Its genomic surveillance is important in cities with millions of inhabitants and an economic center, such as Mexico City. Results. From 16 November to 31 December 2021, we observed an increase of 88% in Omicron prevalence in Mexico City. We explored the R346K substitution, prevalent in 42% of Omicron variants, known to be associated with immune escape by monoclonal antibodies. In a phylogenetic analysis, we found several independent exchanges between Mexico and the world, and there was an event followed by local transmission that gave rise to most of the Omicron diversity in Mexico City. A haplotype analysis revealed that there was no association between haplotype and vaccination status. Among the 66% of patients who have been vaccinated, no reported comorbidities were associated with Omicron; the presence of odynophagia and the absence of dysgeusia were significant predictor symptoms for Omicron, and the RT-qPCR Ct values were lower for Omicron. Conclusions. Genomic surveillance is key to detecting the emergence and spread of SARS-CoV-2 variants in a timely manner, even weeks before the onset of an infection wave, and can inform public health decisions and detect the spread of any mutation that may affect therapeutic efficacy.

Comprehensive omic characterization of breast cancer in Mexican-Hispanic women.

Breast cancer is a heterogeneous pathology, but the genomic basis of its variability remains poorly understood in populations other than Caucasians. Here, through DNA and RNA portraits we explored the molecular features of breast cancers in a set of Hispanic-Mexican (HM) women and compared them to public multi-ancestry datasets. HM patients present an earlier onset of the disease, particularly in aggressive clinical subtypes, compared to non-Hispanic women. The age-related COSMIC signature 1 was more frequent in HM women than in those from other ancestries. We found the AKT1E17K hotspot mutation in 8% of the HM women and identify the AKT1/PIK3CA axis as a potentially druggable target. Also, HM luminal breast tumors present an enhanced immunogenic phenotype compared to Asiatic and Caucasian tumors. This study is an initial effort to include patients from Hispanic populations in the research of breast cancer etiology and biology to further understand breast cancer disparities.

[Spatio-temporal analysis of the biophysical and ecological conditions of Triatoma dimidiata (Hemiptera: Reduviidae: Triatominae) in the northeast region of Colombia].

INTRODUCTION: Due to the lack of information regarding biophysical and spatio-temporal conditions (hydrometheorologic and vegetal coverage density) in areas with Triatoma dimidiata in the Colombian departments of Santander and Boyacá, there is a need to elucidate the association patterns of these variables to determine the distribution and control of this species. OBJECTIVE: To make a spatio-temporal analysis of biophysical variables related to the distribution of T. dimidiate observed in the northeast region of Colombia. MATERIALS AND METHODS: We used the Intergovernmental Panel on Climate Change Special Report on Emissions Scenarios (IPCC SRES) data bases registering vector presence and hydrometheorologic data. We studied the variables of environmental temperature, relative humidity, rainfall and vegetal coverage density at regional and local levels, and we conducted spatial geostatistic, descriptive statistical and Fourier temporal series analyses. RESULTS: Temperatures two meters above the ground and on covered surface ranged from 14,5°C to 18,8°C in the areas with the higher density of T. dimidiata. The environmental temperature fluctuated between 30 and 32°C. Vegetal coverage density and rainfall showed patterns of annual and biannual peaks. Relative humidity values fluctuated from 66,8 to 85,1%. CONCLUSIONS: Surface temperature and soil coverage were the variables that better explained the life cycle of T. dimidiata in the area. High relative humidity promoted the seek of shelters and an increase of the geographic distribution in the annual and biannual peaks of regional rainfall. The ecologic and anthropic conditions suggest that T. dimidiata is a highly resilient species.

Análisis espacio-temporal de las condiciones biofísicas y ecológicasde Triatoma dimidiata (Hemiptera: Reduviidae: Triatominae)en la region nororiental de los Andes de Colombia / Spatio-temporal analysis of the biophysical and ecological conditions of Triatoma dimidiata(Hemiptera: Reduviidae: Triatominae) in the northeast region of Colombia

Resumen Introducción. Ante el desconocimiento del contexto espacio-temporal de las condiciones biofísicas (hidrometereológicas y de densidad de la cobertura vegetal) de las zonas con presencia deTriatoma dimidiata en Santander y Boyacá, es necesario dilucidar los patrones asociados con estas variables para determinar su distribución y control. Objetivo. Hacer el análisis espacio-temporal de las variables biofísicas relacionadas con la distribución de Triatoma dimidiata de los departamentos de Santander y Boyacá en la región nororiental de Colombia. Materiales y métodos. Se utilizaron las bases de datos de los registros de presencia de T. dimidiata y de factores hidrometereológicos del Special Report on Emissions Scenarios (SrES) del Intergovernmental Panel on Climate Change, IPCC. Se estudiaron las variables de temperatura, humedad relativa, pluviosidad y densidad de la cobertura vegetal a nivel regional y local, se hizo el análisis espacial y el geoestadfstico, asf como el análisis estadfstico descriptivo y temporal de las series de Fourier. Resultados. En las áreas con mayor presencia de T. dimidiata, las temperaturas a dos metros del suelo y en suelo cubierto oscilaron entre 14,5 y 18,8 °C, y la temperatura ambiente fue de 30 a 32 °C. La densidad de la cobertura vegetal y la pluviosidad en las áreas de mayor presencia de T. dimidiata exhibieron patrones de picos anuales y bienales. Los valores de la humedad relativa fluctuaron entre 66,8 y 85,1 %. Conclusiones. Las temperaturas a nivel de superficie y a dos metros del suelo fueron las variables determinantes de la distribución espacio-temporal de T. dimidiata. La elevada humedad relativa incentivó la búsqueda de refugios e incrementó la distribución geográfica en los picos anual y bienal de pluviosidad a nivel regional. Las condiciones ecológicas y antrópicas sugieren que T. dimidiata es una especie de gran resiliencia.

Abstract Introduction: Due to the lack of information regarding biophysical and spatio-temporal conditions (hydrometheorologic and vegetal coverage density) in areas with Triatoma dimidiata in the Colombian departments of Santander and Boyacá, there is a need to elucidate the association patterns of these variables to determine the distribution and control of this species. Objective: To make a spatio-temporal analysis of biophysical variables related to the distribution of T. dimidiate observed in the northeast region of Colombia. Materials and methods: We used the Intergovernmental Panel on Climate Change Special Report on Emissions Scenarios (IPCC SRES) data bases registering vector presence and hydrometheorologic data. We studied the variables of environmental temperature, relative humidity, rainfall and vegetal coverage density at regional and local levels, and we conducted spatial geostatistic, descriptive statistical and Fourier temporal series analyses. Results: Temperatures two meters above the ground and on covered surface ranged from 14,5°C to 18,8°C in the areas with the higher density of T. dimidiata. The environmental temperature fluctuated between 30 and 32°C. Vegetal coverage density and rainfall showed patterns of annual and biannual peaks. Relative humidity values fluctuated from 66,8 to 85,1%. Conclusions: Surface temperature and soil coverage were the variables that better explained the life cycle of T. dimidiata in the area. High relative humidity promoted the seek of shelters and an increase of the geographic distribution in the annual and biannual peaks of regional rainfall. The ecologic and anthropic conditions suggest that T. dimidiata is a highly resilient species.

Aplicación precoz de presión positiva continua en el tratamiento de la infección respiratoria aguda baja moderada-grave en pacientes menores de 2 años / Early use of continuous positive airway pressure in the treatment of moderate to severe acute lower respiratory tract infections among patients younger than 2 years old

Objetivo. Analizar las características de los pacientes menores de 2 años que padecieron una infección respiratoria aguda baja moderada-grave tratados precozmente con presión positiva continua en la vía aérea de burbuja y los factores asociados al éxito de la intervención. Método. Estudio retrospectivo y descriptivo. Niños menores de 2 años internados en Cuidados Intermedios Pediátricos del Hospital Provincial Neuquén entre junio de 2009 y diciembre de 2010. Se aplicó presión positiva continua en la vía aérea de burbuja y se midieron frecuencias cardíacas y respiratorias, puntaje de Tal, saturación y fracción inspirada de oxígeno a las 0, 2, 6, 24 y 48 h. Resultados. Se incluyeron 120 pacientes. La mediana de edad fue 3 meses. La intervención fue exitosa en el 72% de los casos. A las 2 h, un descenso del 15% de la frecuencia respiratoria y de 2 puntos en el puntaje de Tal fueron predictores del éxito, con un OR 6,41 (IC 95%: 2,68-15,36) y 9,07 (IC 95%: 3,72-22,19), respectivamente.Conclusiones. La disminución de la frecuencia respiratoria, de la frecuencia cardíaca y del puntaje de Tal a las 2 horas de inicio fueron predictores de éxito.

Objective. To analyze the characteristics of patients younger than 2 years old who had a moderate to severe acute lower respiratory tract infection and were treated early with bubble continuous positive airway pressure, and factors associated with a successful intervention. Method. Retrospective and descriptive study. Children younger than 2 years old admitted to the Pediatric Intermediate Care Unit of Hospital Provincial Neuquen between June 2009 and December 2010. Bubble continuous positive airway pressure was used, and the following outcomes were measured: heart rate, respiratory rate, Tal's score, oxygen saturation, and fraction of inspired oxygen at 0, 2, 6, 24, and 48 h. Results. One hundred and twenty patients were included. Their median age was 3 months old. The intervention was successful in 72% of patients. At 2 h, a 15% reduction in respiratory rate, and a 2-point decrease in Tal's score were predictors of success, with an odds ratio of 6.41 (95% confidence interval: 2.68-15.36), and of 9.07 (95% confidence interval: 3.72-22.19), respectively. Conclusions. A reduction in respiratory rate, heart rate, and Tal's score at 2 hours of starting the intervention were predictors of success.

Early use of continuous positive airway pressure in the treatment of moderate to severe acute lower respiratory tract infections among patients younger than 2 years old. / Aplicación precoz de presión positiva continua en el tratamiento de la infección respiratoria aguda baja moderada-grave en pacientes menores de 2 años.

OBJETIVE: To analyze the characteristics of patients younger than 2 years old who had a moderate to severe acute lower respiratory tract infection and were treated early with bubble continuous positive airway pressure, and factors associated with a successful intervention. METHOD: Retrospective and descriptive study. Children younger than 2 years old admitted to the Pediatric Intermediate Care Unit of Hospital Provincial Neuquen between June 2009 and December 2010. Bubble continuous positive airway pressure was used, and the following outcomes were measured: heart rate, respiratory rate, Tal's score, oxygen saturation, and fraction of inspired oxygen at 0, 2, 6, 24, and 48 h. RESULTS: One hundred and twenty patients were included. Their median age was 3 months old. The intervention was successful in 72% of patients. At 2 h, a 15% reduction in respiratory rate, and a 2-point decrease in Tal's score were predictors of success, with an odds ratio of 6.41 (95% confidence interval: 2.68-15.36), and of 9.07 (95% confidence interval: 3.72-22.19), respectively. CONCLUSIONS: A reduction in respiratory rate, heart rate, and Tal's score at 2 hours of starting the intervention were predictors of success.

OBJETIVO: Analizar las características de los pacientes menores de 2 años que padecieron una infección respiratoria aguda baja moderada-grave tratados precozmente con presión positiva continua en la vía aérea de burbuja y los factores asociados al éxito de la intervención.Estudio retrospectivo y descriptivo. Niños menores de 2 años internados en Cuidados Intermedios Pediátricos del Hospital Provincial Neuquén entre junio de 2009 y diciembre de 2010. Se aplicó presión positiva continua en la vía aérea de burbuja y se midieron frecuencias cardíacas y respiratorias, puntaje de Tal, saturación y fracción inspirada de oxígeno a las 0, 2, 6, 24 y 48 h. RESULTADOS: Se incluyeron 120 pacientes. La mediana de edad fue 3 meses. La intervención fue exitosa en el 72% de los casos. A las 2 h, un descenso del 15% de la frecuencia respiratoria y de 2 puntos en el puntaje de Tal fueron predictores del éxito, con un OR 6,41 (IC 95%: 2,68-15,36) y 9,07 (IC 95%: 3,72-22,19), respectivamente. CONCLUSIONES: La disminución de la frecuencia respiratoria, de la frecuencia cardíaca y del puntaje de Tal a las 2 horas de inicio fueron predictores de éxito.

Exploring the distribution of genetic markers of pharmacogenomics relevance in Brazilian and Mexican populations.

Studies of pharmacogenomics-related traits are increasingly being performed to identify loci that affect either drug response or susceptibility to adverse drug reactions. However, the effect of the polymorphisms can differ in magnitude or be absent depending on the population being assessed. We used the Affymetrix Drug Metabolizing Enzymes and Transporters (DMET) Plus array to characterize the distribution of polymorphisms of pharmacogenetics and pharmacogenomics (PGx) relevance in two samples from the most populous Latin American countries, Brazil and Mexico. The sample from Brazil included 268 individuals from the southeastern state of Rio de Janeiro, and was stratified into census categories. The sample from Mexico comprised 45 Native American Zapotecas and 224 self-identified Mestizo individuals from 5 states located in geographically distant regions in Mexico. We evaluated the admixture proportions in the Brazilian and Mexican samples using a panel of Ancestry Informative Markers extracted from the DMET array, which was validated with genome-wide data. A substantial variation in ancestral proportions across census categories in Brazil, and geographic regions in Mexico was identified. We evaluated the extent of genetic differentiation (measured as FST values) of the genetic markers of the DMET Plus array between the relevant parental populations. Although the average levels of genetic differentiation are low, there is a long tail of markers showing large frequency differences, including markers located in genes belonging to the Cytochrome P450, Solute Carrier (SLC) and UDP-glucuronyltransferase (UGT) families as well as other genes of PGx relevance such as ABCC8, ADH1A, CHST3, PON1, PPARD, PPARG, and VKORC1. We show how differences in admixture history may have an important impact in the distribution of allele and genotype frequencies at the population level.

[Hereditary angioedema: strange cause of abdominal pain]. / Angioedema hereditario: causa rara de dolor abdominal.

BACKGROUND: Hereditary angioedema is an episodic swelling disorder with autosomal dominant inheritance characterized by sudden attacks of peripheral swelling. Patients also commonly have episodic swelling of the wall of hollow viscera, including the bowel. CLINICAL CASE: We present a 33-year-old previously healthy male with a complaint of acute-onset intense abdominal pain localized in the epigastrium. Pain irradiated to the right lower quadrant and was associated with five episodes of vomiting. Computed tomography showed thickening of the duodenal wall with liquid in the subphrenic space. Complementary laboratory tests showed low C4 complement levels (5.5 mg/dl) and 30% complement C1 inhibitor activity. CONCLUSIONS: Hereditary angioedema is caused by a deficiency (type I) or dysfunction (type II) in complement C1 inhibitor. Abdominal associated with angioedema may manifest as severe acute-onset abdominal pain or as moderately severe chronic recurrent abdominal pain. Two medications are currently FDA-approved for the treatment of these patients.

Antecedentes: el angioedema hereditario es un trastorno inflamatorio episódico, que se hereda de manera autosómica dominante y se caracteriza por episodios de edema periférico. Los pacientes pueden tener edema de la pared de cualquier víscera hueca, incluido el intestino. Caso clínico: se comunica el caso de un paciente masculino de 33 años de edad, sin antecedentes de importancia, con dolor abdominal, localizado en el epigastrio, irradiado al cuadrante inferior derecho, acompañado de 5 vómitos. La tomografía abdominal mostró engrosamiento de la pared de la segunda y tercera porción del duodeno, con infiltración de grasa y líquido libre. Los exámenes de laboratorio mostraron: concentraciones bajas del complemento C4 (5.5 mg/dL) y actividad del inhibidor de C1 del complemento de 30%. Conclusiones: el angioedema hereditario es consecuencia de la deficiencia (tipo I) o disfunción (tipo II) del inhibidor C1 del complemento. El dolor abdominal asociado con angioedema es de inicio súbito, como dolor cólico, recurrente y de intensidad moderada. En la actualidad existen dos medicamentos aprobados por la Food and Drug Administration para el tratamiento de pacientes con esta afección.

Neurocysticercosis: the effectiveness of the cysticidal treatment could be influenced by the host immunity.

Neurocysticercosis, a clinically and radiologically pleomorphic parasitic disease, is still endemic to most non-developed countries of Latin America, Africa, and Asia. Anti-helminthic drugs (AHD) are generally effective and rapidly destroy parenchymal cysticerci. In contrast, several cycles of AHD are frequently necessary to damage extraparenchymally located parasites. The present study was designed to evaluate whether differences in the immunological profile of the patients is involved in the diversity of the response to AHD. To this end, a global gene expression microarray and a cytokine analysis were made. Responder patients were those showing a radiological reduction greater than 50 % in the parasite burden following AHD treatment. Microarray pre- and post-treatment comparisons showed that a total of eighteen immune-related genes were up-regulated in the five responder patients with respect the expression profile seen in the four non-responder subjects. The function of up-regulated genes exerted pro-inflammatory (RORγC, Sema4A, SLAMF3, SLAMF6), anti-inflammatory (TGFß, TNFRSF25, TNFRS18, SLAMF1, ILF2), or immunomodulatory effects (CXCL2, RUNX3, SLAMF9, TGFBR3). To further explore the causes of the heterogeneity in the response to treatment, a wide ELISA cytokine analysis was performed in serum, PBMC supernatants, and CSF samples from 39 responder and 26 non-responder patients. Responder patients showed higher CSF IL-17A levels (P = 0.04) and higher supernatant IL-6 levels (P = 0.03) 60 days after treatment. These results suggest a possible influence of pro-inflammatory cytokines on the response to AHD as observed by radiological methods, and thus the possible participation of the host immunity in the effectiveness of AHD treatment.

Pure trisomy 2p syndrome in two siblings with an unbalanced translocation and minimal terminal 12q monosomy characterized by high-density microarray.

Pure partial trisomy 2p patients have rarely been reported. Oligonucleotide array analysis has proved to be important for examining 2p rearrangements to delineate the involved segment and to rule out additional imbalances modifying the phenotype. Here, we report 2 siblings with an unbalanced translocation that led to a partial trisomy 2p (p22.3pter) and a terminal deletion of 12q (q24.33qter). This finding was characterized by the molecular karyotyping of both siblings. The 12q loss spanned approximately 300 kb and did not yield clinical features in our patients. The trisomic region in the short arm of chromosome 2 spanned 32.8 Mb and yielded phenotypic features of pure distal 2p trisomy, notably facial anomalies, growth failure, and psychomotor delay. The clinical features of our patients help to delineate the phenotype of the pure trisomy 2p syndrome. Patient 2 also showed a horseshoe kidney which is a previously unrecognized defect associated with this syndrome.

Cysticerci drive dendritic cells to promote in vitro and in vivo Tregs differentiation.

Regulatory T cells (Tregs) play a crucial role in immune homeostasis. Treg induction is a strategy that parasites have evolved to modulate the host's inflammatory environment, facilitating their establishment and permanence. In human Taenia solium neurocysticercosis (NC), the concurrence of increased peripheral and central Treg levels and their capacity to inhibit T cell activation and proliferation support their role in controlling neuroinflammation. This study is aimed at identifing possible mechanisms of Treg induction in human NC. Monocyte-derived dendritic cells (DC) from healthy human donors, cocultivated with autologous CD4(+) naïve cells either in the presence or absence of cysticerci, promoted CD25(high)Foxp3+ Treg differentiation. An increased Treg induction was observed when cysticerci were present. Moreover, an augmentation of suppressive-related molecules (SLAMF1, B7-H1, and CD205) was found in parasite-induced DC differentiation. Increased Tregs and a higher in vivo DC expression of the regulatory molecules SLAMF1 and CD205 in NC patients were also found. SLAMF1 gene was downregulated in NC patients with extraparenchymal cysticerci, exhibiting higher inflammation levels than patients with parenchymal parasites. Our findings suggest that cysticerci may modulate DC to favor a suppressive environment, which may help parasite establishment, minimizing the excessive inflammation, which may lead to tissue damage.

Resveratrol induces downregulation of DNA repair genes in MCF-7 human breast cancer cells.

To gain insights into the antitumor mechanisms of resveratrol (RES), we carried out a DNA microarray analysis in the breast cancer cell line MCF-7 to study the global gene expression profile induced by RES treatment. The mRNA expression level of 19 734 well-characterized human genes from MCF-7 cells was determined using Affymetrix microarrays under two different RES treatments: 150 µmol/l (IC(50)) and 250 µmol/l during 48 h. A total of 1211 genes were found to have altered mRNA expression levels of two-fold or more in the 150 µmol/l RES-treated group (518 upregulated and 693 downregulated genes). However, 2412 genes were found to have altered expression levels of two-fold or more in the 250 µmol/l RES-treated group (651 genes upregulated and 1761 downregulated). Under both conditions of RES treatment, several genes of mismatch repair, DNA replication, homologous recombination (HR), and cell cycle were strongly inhibited. Consistently, we found decreased protein levels of the MRN complex (MRE11-NBS1-RAD50), an important complex of the HR DNA repair pathway. The ability to inhibit the expression of DNA repair genes by RES could help to overcome drug resistance commonly shown by transformed cells and to provide a solid basis for carrying out clinical trials with RES, alone or in combination with other agents, to enhance treatment efficacy, reduce toxicity, and overcome chemoresistance. Remarkably, after RES treatment, we found a decrease in NBS1 and MRE11 protein levels, two major proteins involved in HR, which suggests that RES could be used to sensitize cancer cells to cell death in combination with anticancer drugs.

Sequence analysis of mutations and translocations across breast cancer subtypes.

Breast carcinoma is the leading cause of cancer-related mortality in women worldwide, with an estimated 1.38 million new cases and 458,000 deaths in 2008 alone. This malignancy represents a heterogeneous group of tumours with characteristic molecular features, prognosis and responses to available therapy. Recurrent somatic alterations in breast cancer have been described, including mutations and copy number alterations, notably ERBB2 amplifications, the first successful therapy target defined by a genomic aberration. Previous DNA sequencing studies of breast cancer genomes have revealed additional candidate mutations and gene rearrangements. Here we report the whole-exome sequences of DNA from 103 human breast cancers of diverse subtypes from patients in Mexico and Vietnam compared to matched-normal DNA, together with whole-genome sequences of 22 breast cancer/normal pairs. Beyond confirming recurrent somatic mutations in PIK3CA, TP53, AKT1, GATA3 and MAP3K1, we discovered recurrent mutations in the CBFB transcription factor gene and deletions of its partner RUNX1. Furthermore, we have identified a recurrent MAGI3-AKT3 fusion enriched in triple-negative breast cancer lacking oestrogen and progesterone receptors and ERBB2 expression. The MAGI3-AKT3 fusion leads to constitutive activation of AKT kinase, which is abolished by treatment with an ATP-competitive AKT small-molecule inhibitor.

Stray dogs as reservoirs of the zoonotic agents Leptospira interrogans, Trypanosoma cruzi, and Aspergillus spp. in an urban area of Chiapas in southern Mexico.

This investigation determined the presence and prevalence of the zoonotic agents Leptospira interrogans, Trypanosoma cruzi, and Aspergillus spp. in the stray dog population (a total of 224 stray dogs) in an urban area of Southern Mexico. Blood serum samples were taken from all dogs, and root hair samples were taken from dogs with skin lesions and partial alopecia. IgG antibodies for L. interrogans from 10 serovars were detected using the microscopic agglutination test. Immunofluorescence antibody test and Western blot assay were used for serologic diagnosis of T. cruzi. The Sabouraud medium was used to isolate Aspergillus spp. Prevalence of L. interrogans was 4.9%, which was determined by identifying only serovars Pyrogenes, which accounted for 3.6%, and Tarassovi, which constituted 1.3%, with titers from 1:100 to 1:800. Additionally, T. cruzi antibodies were detected in 4.5% of the dogs. Skin lesions were found in 43% of the dogs (98/224), and 35 cultures were positive for Aspergillus spp. (35.7%, p < 0.05, 95% confidence interval 2.45-3.67), identified as A. niger (82.8%), A. flavus (14.3%), and A. terreus (2.9%). This study demonstrates the presence of certain zoonotic agents (bacteria, protozoa, and fungi) in stray dogs living within the studied area. Dogs play an important role in the transmission of diseases that are potentially harmful to humans. Although the prevalence of canine leptospirosis and trypanosomiasis is not high in Southern Mexico compared with other tropical regions of Mexico, the presence of these zoonotic agents in the stray dog population demonstrates that the stray dog population in this region is a significant reservoir and potential source of infection in humans. Special care should be taken when handling stray dogs that exhibit skin lesions with partial alopecia, since a pathological Aspergillus sp. fungus may be present.

Analysis of genomic diversity in Mexican Mestizo populations to develop genomic medicine in Mexico.

Mexico is developing the basis for genomic medicine to improve healthcare of its population. The extensive study of genetic diversity and linkage disequilibrium structure of different populations has made it possible to develop tagging and imputation strategies to comprehensively analyze common genetic variation in association studies of complex diseases. We assessed the benefit of a Mexican haplotype map to improve identification of genes related to common diseases in the Mexican population. We evaluated genetic diversity, linkage disequilibrium patterns, and extent of haplotype sharing using genomewide data from Mexican Mestizos from regions with different histories of admixture and particular population dynamics. Ancestry was evaluated by including 1 Mexican Amerindian group and data from the HapMap. Our results provide evidence of genetic differences between Mexican subpopulations that should be considered in the design and analysis of association studies of complex diseases. In addition, these results support the notion that a haplotype map of the Mexican Mestizo population can reduce the number of tag SNPs required to characterize common genetic variation in this population. This is one of the first genomewide genotyping efforts of a recently admixed population in Latin America.