Frequencies and spectra of aflatoxin B1-induced mutations in liver genomes of NEIL1-deficient mice as revealed by duplex sequencing.

Increased risk for the development of hepatocellular carcinoma (HCC) is driven by a number of etiological factors including hepatitis viral infection and dietary exposures to foods contaminated with aflatoxin-producing molds. Intracellular metabolic activation of aflatoxin B1 (AFB1) to a reactive epoxide generates highly mutagenic AFB1-Fapy-dG adducts. Previously, we demonstrated that repair of AFB1-Fapy-dG adducts can be initiated by the DNA glycosylase NEIL1 and that male Neil1-/- mice were significantly more susceptible to AFB1-induced HCC relative to wild-type mice. To investigate the mechanisms underlying this enhanced carcinogenesis, WT and Neil1-/- mice were challenged with a single, 4 mg/kg dose of AFB1 and frequencies and spectra of mutations were analyzed in liver DNAs 2.5 months post-injection using duplex sequencing. The analyses of DNAs from AFB1-challenged mice revealed highly elevated mutation frequencies in the nuclear genomes of both males and females, but not the mitochondrial genomes. In both WT and Neil1-/- mice, mutation spectra were highly similar to the AFB1-specific COSMIC signature SBS24. Relative to wild-type, the NEIL1 deficiency increased AFB1-induced mutagenesis with concomitant elevated HCCs in male Neil1-/- mice. Our data establish a critical role of NEIL1 in limiting AFB1-induced mutagenesis and ultimately carcinogenesis.

Transición en las enfermedades crónicas gastrointestinales. Del cuidado pediátrico al del adulto / Transition in chronic gastrointestinal diseases. From pediatric to adult care

Los avances tecnológicos y del conocimiento hicieron que un mayor número de pacientes con enfermedad crónica gastrointestinal pasen de ser atendidos por el pediatra al control por los médicos de adultos durante una de las etapas más vulnerables de la vida: la adolescencia. El Grupo de Trabajo de Transición del Comité de Gastroenterología de la Sociedad Argentina de Pediatría realizó una búsqueda de literatura exhaustiva y convocó a especialistas referentes del país, con el objeto de unificar los criterios basados en la evidencia y la experiencia. De esta manera, se proponen una serie de recomendaciones para todo el equipo de salud (pediatra, gastroenterólogo infantil, nutricionista, gastroenterólogo de adultos, psicólogo, enfermería), incluso para pacientes y familias, que faciliten el proceso de transición y optimicen el seguimiento, el control, la prevención de complicaciones y la calidad de vida de los pacientes con enfermedades crónicas gastrointestinales

Technological advances and the globalization of knowledge have led to a considerable increase in the number of patients with chronic gastrointestinal disease who transition from pediatric to adult care during one of the most vulnerable life stages: adolescence. The Transition Working Group of the Gastroenterology Committee of the Sociedad Argentina de Pediatría conducted an exhaustive literature search and summoned leading specialists in the most frequent chronic pathologies from all over the country to unify criteria based on evidence and experience. As a result, a series of recommendations are proposed for the whole health team (pediatrician, pediatric gastroenterologist, nutritionist, adult gastroenterologist, psychologist, and nurse) including patients and families, to facilitate the transition process, optimize follow-up, prevent complications, and improve the quality of life of patients with chronic gastrointestinal diseases.

[Transition in chronic gastrointestinal diseases. From pediatric to adult care]. / Transición en las enfermedades crónicas gastrointestinales. Del cuidado pediátrico al del adulto.

Technological advances and the globalization of knowledge have led to a considerable increase in the number of patients with chronic gastrointestinal disease who transition from pediatric to adult care during one of the most vulnerable life stages: adolescence. The Transition Working Group of the Gastroenterology Committee of the Sociedad Argentina de Pediatría conducted an exhaustive literature search and summoned leading specialists in the most frequent chronic pathologies from all over the country to unify criteria based on evidence and experience. As a result, a series of recommendations are proposed for the whole health team (pediatrician, pediatric gastroenterologist, nutritionist, adult gastroenterologist, psychologist, and nurse) including patients and families, to facilitate the transition process, optimize follow-up, prevent complications, and improve the quality of life of patients with chronic gastrointestinal diseases.

Los avances tecnológicos y del conocimiento hicieron que un mayor número de pacientes con enfermedad crónica gastrointestinal pasen de ser atendidos por el pediatra al control por los médicos de adultos durante una de las etapas más vulnerables de la vida: la adolescencia. El Grupo de Trabajo de Transición del Comité de Gastroenterología de la Sociedad Argentina de Pediatría realizó una búsqueda de literatura exhaustiva y convocó a especialistas referentes del país, con el objeto de unificar los criterios basados en la evidencia y la experiencia. De esta manera, se proponen una serie de recomendaciones para todo el equipo de salud (pediatra, gastroenterólogo infantil, nutricionista, gastroenterólogo de adultos, psicólogo, enfermería), incluso para pacientes y familias, que faciliten el proceso de transición y optimicen el seguimiento, el control, la prevención de complicaciones y la calidad de vida de los pacientes con enfermedades crónicas gastrointestinales.

Mutación DGAT1 en dos hermanas con falla de medro: reporte de caso / DGAT1 mutation in two sisters with failure to thrive: a case report

Las diarreas y enteropatías congénitas (CODE por su sigla en inglés) son un grupo de trastornos monogénicos que se han descrito en los últimos años. Dentro de las CODE, la mutación del gen de la diacilglicerol o-aciltransferasa 1 (DGAT1) es un trastorno enzimático poco común asociado con diarrea crónica grave de aparición temprana. El objetivo es presentar a dos hermanas que consultaron por diarrea crónica, retraso en el crecimiento, vómitos e hipoalbuminemia en la primera infancia. En ambas pacientes se encontró un compuesto heterocigota de la mutación del DGAT1. Esta mutación se describió previamente en la población asiática; sin embargo, estas son las dos primeras pacientes en tener esta mutación en la población latinoamericana. Estos dos casos pueden ampliar nuestro conocimiento sobre las diarreas congénitas en general y las características clínicas de los pacientes con mutaciones en DGAT1 en particular.

Congenital diarrhea and enteropathies (CODEs) are a group of monogenic disorders that have been described in recent years. Within the CODEs, the mutation in the diacylglycerol O-acyltransferase 1 (DGAT1) gene is a rare enzyme disorder associated with severe, early-onset chronic diarrhea. Our objective is to describe the case of 2 sisters who consulted for chronic diarrhea, growth retardation, vomiting, and hypoalbuminemia in early childhood. A compound heterozygous DGAT1 mutation was found in both patients. This mutation was previously described in the Asian population; however, these are the first 2 patients to show this mutation in the Latin American population. These 2 cases may expand our knowledge about congenital diarrhea in general and the clinical characteristics of patients with DGAT1 mutations in particular.

Enfoque integral en el diagnóstico del patrón esquelético maxilomandibular, la postura corporal y cráneo-cervical / A comprehensive approach to the diagnosis of the maxillomandibular skeletal pattern, body posture and craniocervical position

Introducción: Los principios biomecánicos de cabeza y cuello cobran un interés especial en el campo de la ortodoncia y la ortopedia dentomaxilofacial. Cualquier anomalía debe ser analizada y tratada dentro del sistema cráneo-cérvico-mandibular con un enfoque integral. Objetivo: Describir la relación entre el patrón esquelético maxilomandibular sagital, la postura corporal y la posición cráneo-cervical en adolescentes. Métodos: Estudio descriptivo, transversal, desarrollado entre marzo del 2018 a junio del 2019. La muestra estuvo conformada por 105 adolescentes del séptimo grado de la ESBU "Eduardo Anoceto Rega", de Santa Clara. Se determinó el patrón esquelético maxilomandibular de clase I, II y III midiendo la convexidad facial del cefalogramas de Ricketts; la posición cráneo-cervical de extensión, normoinclinación y flexión con el cefalograma de Rocabado; el tipo de postura con el método de Bricot. Se siguieron las normas éticas y fueron aplicados los estadígrafos chi cuadrado, F de Fisher y estadístico de Welch. Resultados: La postura D (espalda plana y plano escapular anterior) predominó en todas las clases esqueléticas 64,76 por ciento de los adolescentes, seguido de la postura C (plano escapular posterior). En la clase II, después de la postura D siguió la postura B (plano escapular y glúteo alineados con aumento de las curvas anteriores) con un 6,22 por ciento. Predominó la normoinclinación cráneo-cervical 46,67 por ciento y la flexión 42,86 por ciento. En la clase III predominó la flexión y el ángulo posteroinferior de Rocabado mayor respecto a las otras clases esqueléticas de 107º. Conclusiones: La posición del cráneo respecto a las estructuras cervicales, asociada a las características de cada clase esquelética, puede ser un indicador importante en el diagnóstico morfológico. A pesar de las muchas investigaciones en este campo, aún no se puede hablar de consenso en cuanto al grado de relación entre la postura craneocervical y las maloclusiones(AU)

Introduction: Head and neck biomechanical principles are particularly relevant in the fields of orthodontics and dentomaxillofacial orthopedics. Any anomaly should be analyzed and treated within the cranio-cervical-mandibular system applying a comprehensive approach. Objective: Describe the relationship between the sagittal maxillomandibular skeletal pattern, body posture and craniocervical position in adolescents. Methods: A descriptive cross-sectional study was conducted from March 2018 to June 2019. The study sample was 105 adolescents attending seventh grade at Eduardo Anoceto Rega junior high school in Santa Clara. Determination was made of maxillomandibular skeletal patterns Classes I, II and III, measuring the facial convexity in Ricketts' cephalograms, craniocervical extension, normal inclination and flexion positions with Rocabado's cephalogram, and posture type with Bricot's method. Ethical standards were complied with. Use was made of the statistical tests chi-square, Fisher's F and Welch's. Results: Posture D (flat back and anterior scapular plane) prevailed in all skeletal classes: 64.76 percent of the adolescents, followed by posture C (posterior scapular plane). In Class II, posture D was followed by posture B (scapular and gluteal plane aligned with increased anterior curves): 6.22 percent. A predominance was observed of craniocervical normal inclination: 46.67 percent and flexion: 42.86 percent. In Class III, Rocabado's flexion and posteroinferior angle were more common than the remaining 107º skeletal classes. Conclusions: Cranial position with respect to cervical structures, according to the characteristics of each skeletal class, may be an important indicator in morphological diagnosis. Despite the large number of studies conducted in this field, consensus has not been achieved about the degree of relationship between craniocervical posture and malocclusions(AU)

Guía de práctica clínica Ibero-Latinoamericana sobre la esofagitis cáustica en Pediatría: aspectos terapéuticos (2a. Parte) / Ibero-Latinamerican Clinical Practical Guidelines on pediatric caustic esophagitis: therapeutical aspects (Part 2)

Resumen: La ingestión de cáusticos representa un grave problema médico-social por las consecuencias devastadoras e irreversibles que puede producir en el tracto digestivo superior. En Iberoamérica no se han publicado datos fidedignos sobre la incidencia o la prevalencia de lesiones inducidas por cáusticos. La información disponible sobre la presentación clínica, diagnóstico, tratamiento y pronóstico se basa en series retrospectivas de casos y, de hecho, su manejo clínico se sustenta en muchos casos fundamentalmente en la opinión de expertos. Recientemente como una iniciativa de la Sociedad Latinoamericana de Gastroenterología, Hepatología y Nutrición Pediátrica (SLAGHNP) y con la co laboración de colegas de la Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediá trica (SEGHNP), hemos diseñado una Guía de Práctica Clínica (GPC) la cual incluye una serie de enunciados y recomendaciones dirigidos a optimizar la atención a los pacientes y que se basan en la revisión sistemática de la evidencia. En dos (2) manuscritos sucesivos nos hemos enfocado primero, en los aspectos fisiopatológicos y de diagnóstico clínico-endoscópico de la esofagitis cáustica en niños (1a. Parte) y en segundo lugar, en los aspectos más relevantes del tratamiento (2a. Parte). Esperamos esta guía se convierta en una herramienta útil para el clínico en el difícil proceso de toma de decisio nes a la hora de evaluar un paciente posterior a la ingesta de una sustancia cáustica.

Abstract: Caustic ingestion represents a serious social-medical problem due to the devastating and irreversible consequences it can produce in the upper digestive tract. In Ibero-America, there are no published reliable data on the incidence or prevalence of caustic-induced injuries, and most of the available information on clinical presentation, diagnosis, treatment, and prognosis is based on retrospective clinical series and, indeed, its clinical management is often based primarily on expert opinion. Re cently as an initiative of the Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition (LASPGHAN) and with the cooperation of the Spanish Society for Pediatric Gastroente rology, Hepatology and Nutrition (SEGHNP), we have designed a Clinical Practice Guideline that include a series of statements and recommendations aimed at optimizing patient medical care which is based on the systematic review of evidence. Two (2) separate papers focused on the evaluation of physiopathological and clinical-endoscopic diagnostic features of caustic esophagitis in children (1st. Paper) and, on the other hand, the most relevant therapeutic considerations (2nd. Paper). We expect this guideline to become a useful tool for the physician in the difficult decision-making process when assessing patients after caustic ingestion.

Guía de práctica clínica Ibero-Latinoamericana sobre la esofagitis cáustica en Pediatría: fisiopatología y diagnóstico clínico-endoscópico (1a Parte) / Ibero-latinamerican clinical practical guidelines on pediatric caustic esophagitis: physiopathology and clinical-endoscopic diagnosis (1st Part)

Resumen: La ingestión de cáusticos representa un grave problema médico-social por las consecuencias devastadoras e irreversibles que puede producir en el tracto digestivo superior. En Iberoamérica no se han publicado datos fidedignos sobre la incidencia o la prevalencia de lesiones inducidas por cáusticos. La información disponible sobre la presentación clínica, diagnóstico, tratamiento y pronóstico se basa en series retrospectivas de casos y, de hecho, su manejo clínico se sustenta en muchos casos fundamentalmente en la opinión de expertos. Recientemente como una iniciativa de la Sociedad Latinoamericana de Gastroenterología, Hepatología y Nutrición Pediátrica (SLAGHNP) y con la co laboración de colegas de la Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediá trica (SEGHNP), hemos diseñado una Guía de Práctica Clínica (GPC) la cual incluye una serie de enunciados y recomendaciones dirigidos a optimizar la atención a los pacientes y que se basan en la revisión sistemática de la evidencia. En dos (2) manuscritos sucesivos nos hemos enfocado primero, en los aspectos fisiopatológicos y de diagnóstico clínico-endoscópico de la esofagitis cáustica en niños (1a. Parte) y en segundo lugar, en los aspectos más relevantes del tratamiento (2a. Parte). Esperamos esta guía se convierta en una herramienta útil para el clínico en el difícil proceso de toma de decisio nes a la hora de evaluar un paciente posterior a la ingesta de una sustancia cáustica.

Abstract: Caustic ingestion represents a serious social-medical problem due to the devastating and irreversible consequences it can produce in the upper digestive tract. In Ibero-America, there are no published reliable data on the incidence or prevalence of caustic-induced injuries, and most of the available information on clinical presentation, diagnosis, treatment, and prognosis is based on retrospective clinical series and, indeed, its clinical management is often based primarily on expert opinion. Re cently as an initiative of the Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition (LASPGHAN) and with the cooperation of the Spanish Society for Pediatric Gastroente rology, Hepatology and Nutrition (SEGHNP), we have designed a Clinical Practice Guideline that include a series of statements and recommendations aimed at optimizing patient medical care which is based on the systematic review of evidence. Two (2) successive papers focused on the evaluation of physiopathological and clinical-endoscopic diagnostic features of caustic esophagitis in children (1st. Paper) and, on the other hand, the most relevant therapeutic considerations (2nd. Paper). We expect this guideline to become a useful tool for the physician in the difficult decision-making process when assessing patients after caustic ingestion.

APOE ε2 is associated with increased tau pathology in primary tauopathy.

Apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease mainly by modulating amyloid-ß pathology. APOE ε4 is also shown to exacerbate neurodegeneration and neuroinflammation in a tau transgenic mouse model. To further evaluate the association of APOE genotype with the presence and severity of tau pathology, we express human tau via an adeno-associated virus gene delivery approach in human APOE targeted replacement mice. We find increased hyperphosphorylated tau species, tau aggregates, and behavioral abnormalities in mice expressing APOE ε2/ε2. We also show that in humans, the APOE ε2 allele is associated with increased tau pathology in the brains of progressive supranuclear palsy (PSP) cases. Finally, we identify an association between the APOE ε2/ε2 genotype and risk of tauopathies using two series of pathologically-confirmed cases of PSP and corticobasal degeneration. Our data together suggest APOE ε2 status may influence the risk and progression of tauopathy.

Changes in the Gut Microbiota of Urban Subjects during an Immersion in the Traditional Diet and Lifestyle of a Rainforest Village.

People living traditional lifestyles have higher gut microbiota diversity than urban subjects. We hypothesized that shifting lifestyles from an urban environment to a traditional rainforest village would lead to changes in the microbiota of visitors, which would become more similar to the microbiota of villagers. Here, we characterized at different time points the microbiota of 7 urban visitors (5 adults and 2 children) staying in a rainforest Amerindian village for 16 days and compared them with a reference collection of samples from age-matched local villagers. We performed a 16S rRNA gene survey of samples from multiple body sites (including fecal, oral, nasal, and skin samples) using Illumina MiSeq sequencing. The main factor segregating the microbiotas of each body site was the human group (i.e., visitors versus villagers), with the visitor microbiota tending to have lower alpha diversity; the lowered alpha diversity was statistically significant in the microbiota of skin and in the children's fecal and oral microbiota. During the rainforest period, all visitors experienced microbiota changes within their personal cloud of variation. For all body sites, the microbiota conformations in the visitor children better matched the microbiota conformations in villagers of the same age than did those of the visitor adults, which showed a lower "microbiota age" than the microbiota of the villagers. The results suggest higher stability in the adult microbiota, with the less resilient children's microbiota responding more to dietary changes.IMPORTANCE Despite the limitations of a small study, our results evidence higher resilience of the gut microbiota with respect to dietary manipulation in adults than in children and urge further studies to understand the extent of microbiota plasticity in response to dietary changes and the mechanisms underlying microbiota resilience. These studies are relevant to the potential of future human pre- and probiotics in preventing or curing microbiota-associated diseases.

Replication of progressive supranuclear palsy genome-wide association study identifies SLCO1A2 and DUSP10 as new susceptibility loci.

BACKGROUND: Progressive supranuclear palsy (PSP) is a parkinsonian neurodegenerative tauopathy affecting brain regions involved in motor function, including the basal ganglia, diencephalon and brainstem. While PSP is largely considered to be a sporadic disorder, cases with suspected familial inheritance have been identified and the common MAPT H1haplotype is a major genetic risk factor. Due to the relatively low prevalence of PSP, large sample sizes can be difficult to achieve, and this has limited the ability to detect true genetic risk factors at the genome-wide statistical threshold for significance in GWAS data. With this in mind, in this study we genotyped the genetic variants that displayed the strongest degree of association with PSP (P<1E-4) in the previous GWAS in a new cohort of 533 pathologically-confirmed PSP cases and 1172 controls, and performed a combined analysis with the previous GWAS data. RESULTS: Our findings validate the known association of loci at MAPT, MOBP, EIF2AK3 and STX6 with risk of PSP, and uncover novel associations with SLCO1A2 (rs11568563) and DUSP10 (rs6687758) variants, both of which were classified as non-significant in the original GWAS. CONCLUSIONS: Resolving the genetic architecture of PSP will provide mechanistic insights and nominate candidate genes and pathways for future therapeutic intervention strategies.

[Gallstone ileus, surgical management review]. / Íleo biliar, revisión del manejo quirúrgico.

BACKGROUND: Gallstone ileus (GI) represents a rare cause of mechanical intestinal occlusion, which is caused by the impaction of a gallstones at the gastrointestinal tract, being most frequently the terminal ileum; its etiology is due to the passage of a calculum through a biliary-enteric fistula. Due to its low incidence, diagnostic suspicion and adequate initial surgical treatment are essential for an adequate clinical evolution. OBJECTIVE: A bibliographic review on the current surgical management of GI was carried out and exemplified by the presentation a clinical case. CLINICAL CASE: 78-year-old male with bowel obstruction, upon undergoing a CT scan, a gallstone at the level of distal ileum is displayed, therefore, an exploratory laparotomy (ex lap) is performed with enterotomy and extraction of the calculus. The patient bestowed adequate postoperative clinical evolution, and the presence of a cholecystoduodenal fistula is documented by an upper endoscopy. DISCUSSION: GI represents an uncommon pathology, however, there is discrepancy in the literature regarding the initial surgical management, especially in whether or not a biliary procedure should be associated with emergency enterolithotomy. CONCLUSION: GI is associated with complications secondary to diagnostic delay and its late surgical resolution, although the initial treatment is aimed at resolving the intestinal obstruction through enterotomy and gallstone extraction, there is controversy regarding the preferred time for cholecystectomy and repair of biliary-enteric fistula, being the two-stage surgery the surgical procedure of choice, especially in patients with a high risk of complications.

ANTECEDENTES: El íleo biliar (IB) es una causa poco frecuente de oclusión intestinal mecánica, causado por la impactación de un cálculo biliar en el tubo digestivo, siendo la localización más frecuente el íleon terminal; se debe al paso de un cálculo a través de una fístula bilioentérica. Debido a su baja incidencia, la sospecha diagnóstica y el tratamiento quirúrgico inicial adecuado son de gran importancia para la evolución clínica. OBJETIVO: Realizar una revisión bibliográfica sobre el manejo quirúrgico actual del IB y ejemplificarlo mediante la presentación de un caso clínico. CASO CLÍNICO: Varón de 78 años con cuadro de oclusión intestinal, con presencia de cálculo biliar en el íleon distal por tomografía. Se realiza laparotomía exploradora con enterotomía y extracción del cálculo. Cursa con adecuada evolución posquirúrgica, documentándose fístula colecistoduodenal por panendoscopia. DISCUSIÓN: El IB es una patología poco común, por lo cual existe discrepancia en cuanto al tipo de manejo quirúrgico ideal, sobre todo en si se debe o no asociar un procedimiento biliar a la enterolitotomía de urgencia. CONCLUSIÓN: El IB se asocia a complicaciones secundarias al retraso diagnóstico y a una mala elección de la técnica quirúrgica inicial. Si bien el tratamiento está encaminado a resolver la obstrucción intestinal mediante enterotomía y extracción del cálculo biliar, existe controversia en cuanto al tiempo preferido para realizar la colecistectomía y la reparación de la fístula bilioentérica, siendo la cirugía en dos tiempos el procedimiento quirúrgico de elección, sobre todo en pacientes con alto riesgo de complicaciones.

Registro prospectivo durante un año de enfermedad inflamatoria intestinal en población pediátrica argentina / One-year prospective registry of inflammatory bowel disease in the Argentine pediatric population

Introducción. La enfermedad inflamatoria intestinal (EII) comprende la colitis ulcerosa (CU) y la enfermedad de Crohn (EC). Su diagnóstico es cada vez más frecuente en pediatría y la incidencia es desconocida en Argentina. El objetivo de este trabajo fue determinar la incidencia anual de EII en menores de 18 años de nuestro país, los aspectos epidemiológicos y las formas clínicas de presentación. Población y métodos. Estudio prospectivo, multicéntrico y observacional que abarcó todo el territorio nacional. Se incluyeron menores de 18 años con diagnóstico de EII de centros públicos y privados entre el 1/6/2012 y el 31/5/2013, a través de protocolo en la web. Resultados. Participaron 17 centros, y se registraron 50 pacientes en 10 centros. La incidencia fue 0, 4/100 000 < 18 años; EC, 20; CU, 25; y EII no clasificable, 5. Distribución según sexo: 26 varones y 24 mujeres. La edad media al momento del diagnóstico fue de 9, 7 años y la demora diagnóstica, de 16, 5 meses. Los síntomas y signos más frecuentes fueron diarrea crónica con sangre y/o moco, dolor abdominal y adelgazamiento. El retraso del crecimiento fue menor de lo esperado. Las manifestaciones extraintestinales se presentaron en el 24% en CU y en el 25% en EC. La localización más frecuente en EC fue ileocolónica, y, en CU, pancolónica. No se observó CU con formas graves. Conclusiones. La incidencia fue menor que la reportada por otros registros. Se considera conveniente la creación de un registro permanente, que no solo permita conocer la incidencia, sino también servir de apoyo a los centros referentes que diagnostican y tratan esta patología.

Introduction. Inflammatory bowel disease (IBD) includes ulcerative colitis (UC) and Crohn's disease (CD). IBD diagnosis has become increasingly common in pediatrics but its incidence is unknown in Argentina. The objective of this study was to determine the annual incidence of IBD in children and adolescents younger than 18 years in Argentina, its epidemiological aspects, and clinical presentations. Population and methods. Prospective, observational, multicenter study conducted in Argentina. Children and adolescents younger than 18 years from public and private facilities, diagnosed with IBD between June 1st, 2012 and May 31st, 2013 were included via a web protocol. Results. Seventeen sites participated in the study; 50 patients were recruited from 10 sites. IBD incidence was 0.4/100 000 among individuals <18 years; CD, 20; UC, 25; and idiopathic IBD, 5. Distribution by sex: 26 boys and 24 girls. Patients' mean age at diagnosis was 9.7 years, and delay in the diagnosis was 16.5 months. The most common symptoms and signs were chronic diarrhea with blood and/or mucus, abdominal pain, and weight loss. Growth retardation was less common than expected. Extraintestinal manifestations were observed in 24% of UC cases and in 25% of CD cases. The most common location of CD was the ileum and colon, and of UC was the entire colon (pancolonic). There were no cases with severe UC. Conclusions. The incidence was lower than that reported in other registries. We recommend the development of an ongoing registry, to establish the incidence of IBD, but also to serve as backup for referring facilities where this disease is diagnosed and treated.

One-year prospective registry of inflammatory bowel disease in the Argentine pediatric population. / Registro prospectivo durante un año de enfermedad inflamatoria intestinal en población pediátrica argentina.

INTRODUCTION: Inflammatory bowel disease (IBD) includes ulcerative colitis (UC) and Crohn's disease (CD). IBD diagnosis has become increasingly common in pediatrics but its incidence is unknown in Argentina. The objective of this study was to determine the annual incidence of IBD in children and adolescents younger than 18 years in Argentina, its epidemiological aspects, and clinical presentations. POPULATION AND METHODS: Prospective, observational, multicenter study conducted in Argentina. Children and adolescents younger than 18 years from public and private facilities, diagnosed with IBD between June 1st, 2012 and May 31st, 2013 were included via a web protocol. RESULTS: Seventeen sites participated in the study; 50 patients were recruited from 10 sites. IBD incidence was 0.4/100 000 among individuals <18 years; CD, 20; UC, 25; and idiopathic IBD, 5. Distribution by sex: 26 boys and 24 girls. Patients' mean age at diagnosis was 9.7 years, and delay in the diagnosis was 16.5 months. The most common symptoms and signs were chronic diarrhea with blood and/or mucus, abdominal pain, and weight loss. Growth retardation was less common than expected. Extraintestinal manifestations were observed in 24% of UC cases and in 25% of CD cases. The most common location of CD was the ileum and colon, and of UC was the entire colon (pancolonic). There were no cases with severe UC. CONCLUSIONS: The incidence was lower than that reported in other registries. We recommend the development of an ongoing registry, to establish the incidence of IBD, but also to serve as backup for referring facilities where this disease is diagnosed and treated.

INTRODUCCIÓN: La enfermedad inflamatoria intestinal (EII) comprende la colitis ulcerosa (CU) y la enfermedad de Crohn (EC). Su diagnóstico es cada vez más frecuente en pediatría y la incidencia es desconocida en Argentina. El objetivo de este trabajo fue determinar la incidencia anual de EII en menores de 18 años de nuestro país, los aspectos epidemiológicos y las formas clínicas de presentación. POBLACIÓN Y MÉTODOS: Estudio prospectivo, multicéntrico y observacional que abarcó todo el territorio nacional. Se incluyeron menores de 18 años con diagnóstico de EII de centros públicos y privados entre el 1/6/2012 y el 31/5/2013, a través de protocolo en la web. RESULTADOS: Participaron 17 centros, y se registraron 50 pacientes en 10 centros. La incidencia fue 0,4/100 000 < 18 años; EC, 20; CU, 25; y EII no clasificable, 5. Distribución según sexo: 26 varones y 24 mujeres. La edad media al momento del diagnóstico fue de 9,7 años y la demora diagnóstica, de 16,5 meses. Los síntomas y signos más frecuentes fueron diarrea crónica con sangre y/o moco, dolor abdominal y adelgazamiento. El retraso del crecimiento fue menor de lo esperado. Las manifestaciones extraintestinales se presentaron en el 24% en CU y en el 25% en EC. La localización más frecuente en EC fue ileocolónica, y, en CU, pancolónica. No se observó CU con formas graves. CONCLUSIONES: La incidencia fue menor que la reportada por otros registros. Se considera conveniente la creación de un registro permanente, que no solo permita conocer la incidencia, sino también servir de apoyo a los centros referentes que diagnostican y tratan esta patología.

Visita virtual a la Facultad de Estomatología: pertinencia en la orientación profesional de la carrera / Virtual visit to the Dentistry Faculty: its pertinence in career professional orientation

Introducción: la orientación profesional a través de medios audiovisuales es una estrategia novedosa y efectiva para motivar a estudiantes en la selección de la carrera de Estomatología. Objetivo: valorar la pertinencia del audiovisual Visita virtual a la Facultad de Estomatología, dirigido a estudiantes de primer año y aspirantes a la carrera, según criterios de especialistas y usuarios. Métodos: se realizó una investigación descriptiva en la Facultad de Estomatología de la Universidad de Ciencias Médicas de Villa Clara. Para ello se emplearon métodos teóricos: análisis-síntesis, histórico-lógico e inductivo-deductivo; y empíricos: la encuesta en forma de cuestionario y de entrevista a los estudiantes. Para la valoración del producto se utilizó el criterio de especialistas y usuarios. Resultados: entre las causas motivadoras de los estudiantes para optar por la carrera predominó la colaboración con otros países; en cuanto a los criterios asumidos sobre la Estomatología: los de primer año tuvieron los mayores aciertos, dados por su participación en el curso introductorio; con respecto a las formas en que recibieron orientación profesional, sobresalen la asistencia masiva a las puertas abiertas por los aspirantes y la escasa participación en círculos de interés por ambos grupos; por lo que se elaboró un recurso audiovisual el cual fue valorado por especialistas y usuarios. Conclusiones: el medio fue valorado como pertinente por el dinamismo de sus secuencias, los efectos visuales, el equilibrio entre los diálogos y su aire juvenil; todo lo cual lo convierte en apropiado para la orientación profesional.

Background: professional orientation through audiovisual media is a novel and effective strategy to motivate students in the enrollment to the Dentistry career. Objective: to assess the pertinence of the audiovisual Virtual visit to the Dentistry Faculty, aimed at first year students and aspirants to the career, according to the criteria of specialists and users. Methods: a descriptive research was carried out at Villa Clara University of Medical Sciences Dentistry Faculty. For this purpose theoretical methods were used: analysis-synthesis, historical-logical and inductive-deductive; and empirical ones: the survey in questionnaire form and an interview was applied to students. The users and specialists´ criteria was used for the assessment of the product. Results: among the motivating causes of the students to opt for the career predominated the collaboration with other countries; In terms of the criteria adopted on Dentistry: the first year students had the greatest success, because of their participation in the introductory course; With regard to the ways in which they received professional orientation, the massive attendance to the opened doors by the aspirants and the low participation in vocational training activities by both groups stand out; For which an audiovisual teaching aid was elaborated which was valued by specialists and users. Conclusions: the teaching aid was valued as relevant by the dynamism of its sequences, the visual effects, the balance between the dialogues and its youthful air; all of which makes it suitable for career professional orientation.

Evaluación in vitro de dos extractos de Aloe vera en bacterias patógenas / In vitro evaluation of two extracts of Aloe vera in pathogenic bacteria

El incremento en los mecanismos de resistencia bacteriana, ha planteado a la comunidad científica la necesidad en la búsqueda de principios activos para producir nuevos antibióticos, donde el Aloe vera se proyecta como una fuente de obtención de los mismos. El objetivo de esta investigación fue evaluar el comportamiento de dos tipos de extractos; uno de gel fresco procesado con DMSO, y otro obtenido del mesofilo por un proceso de extracción con etanol que luego fue filtrado, concentrado y liofilizado. Ambos extractos fueron evaluados con la prueba de susceptibilidad antimicrobiana por difusión en disco contra Helicobacter pylori, Escherichia coli, Enterococcus faecalis, Staphylococcus aureus y Streptococcus mutans. El extracto etanólico del mesófilo liofilizado se ensayó en concentraciones de 0,5; 1,0; 1,5; 2,0 y 2,5 mg/ mL, con cada una de las bacterias de referencia, evidenciándose ausencia de inhibición sobre el crecimiento bacteriano en todas las concentraciones. El extracto Gel-DMSO se ensayó con las cepas H. pylori, E. coli y S. aureus; obteniendo halos de inhibición de 14, 8,5 y 8,5 mm respectivamente. La evidencia científica de la actividad antibacteriana de esta planta suele ser contradictoria, donde el procesamiento del extracto, es un factor importante en esta variabilidad. Según nuestros resultados se puede concluir que H. pylori, fue la bacteria más sensible al extracto Gel-DMSO en comparación con E. coli y S. aureus; asimismo, para futuras investigaciones, se debería desestimar el uso de extractos liofilizados diluidos y considerar otros procesos de extracción.

The increase of bacterial resistance mechanisms has created special interest in the scientific community to search for active principles for the production of new antibiotics, and the Aloe Vera plant has been considered as a potential source to obtain them. The objective of this research was to evaluate the behavior of two types of Aloe Vera extracts, one fresh gel processed with DMSO and other obtained by the mesophyll by ethanol extraction process that was filtered, concentrated and lyophilized. Both extracts were evaluated with antimicrobial susceptibility testing by disc diffusion against Helicobacter pylori, Escherichia coli, Enterococcus faecalis, Staphylococcus aureus and Streptococcus mutans. The ethanolic extract of lyophilized mesophyll was tested in concentrations of 0.5 1.0 1.5 2.0 and 2.5 mg / ml, with each of the reference bacteria, showing no inhibition on bacterial growth in all concentrations tested. Gel-DMSO extract was tested with strains H. pylori, E. coli and S. aureus, obtaining inhibition halos of 14, 8.5 and 8.5 mm respectively. Scientific evidence of the antibacterial activity of this plant can be contradictory, and the processing of the extract is a determining factor in such variability. According to our results, we conclude that H. pylori was the bacteria most sensitive to Gel- DMSO extract compared with E. coli and S. aureus bacteria; also, we advise against the use of diluted and lyophilised extracts is in future research; rather, other alternative extraction process should be considered.

BIOFILM FORMATION OF Vibrio cholerae ON STAINLESS STEEL USED IN FOOD PROCESSING.

Vibrio cholerae represents a significant threat to human health in developing countries. This pathogen forms biofilms which favors its attachment to surfaces and its survival and transmission by water or food. This work evaluated the in vitro biofilm formation of V. cholerae isolated from clinical and environmental sources on stainless steel of the type used in food processing by using the environmental scanning electron microscopy (ESEM). Results showed no cell adhesion at 4 h and scarce surface colonization at 24 h. Biofilms from the environmental strain were observed at 48 h with high cellular aggregations embedded in Vibrio exopolysaccharide (VPS), while less confluence and VPS production with microcolonies of elongated cells were observed in biofilms produced by the clinical strain. At 96 h the biofilms of the environmental strain were released from the surface leaving coccoid cells and residual structures, whereas biofilms of the clinical strain formed highly organized structures such as channels, mushroom-like and pillars. This is the first study that has shown the in vitro ability of V. cholerae to colonize and form biofilms on stainless steel used in food processing.

Bacterias similares a Helicobacter pylori, en aguas de acueductos del estado Táchira y su probable asociación con patología gástrica / Similar bacteria to Helicobacter pylori, in water supplies of Táchira state and its possible association with gastric pathology

Introducción: Helicobacter pylori es uno de los agentes asociado al cáncer gástrico y posee una alta prevalencia en los países en vías de desarrollo. Sus rutas de transmisión no han sido totalmente establecidas; sin embargo, en algunos estudios se ha detectado su ADN en muestras de aguas residuales, subterráneas y superficiales. El objetivo de este trabajo fue detectar el ADN del género Helicobacter en muestras provenientes de acueductos rurales del municipio San Cristóbal y el Acueducto Regional del Táchira (ART). Materiales y métodos: Se recolectaron 500 ml de seis acueductos rurales y el ART. Se determinó la presencia de ADN del género Helicobacter a través de PCR y PCR semianidada con la posterior secuenciación de los productos de reacción. Resultados y discusión: El género Helicobacter no fue detectado mediante PCR, pero se observó la banda esperada en tres muestras mediante una PCR semianidada. La secuenciación de dos amplicones mostraron una similitud del 99% con Ralstonia pickettii, indicando que Helicobacter no fue detectada en los acueductos muestreados. Conclusiones: La secuenciación de los amplicones para el género Helicobacter, mostraron que se trata de R. pickettii un patógeno oportunista, con características similares a H. pylori.

Background: Helicobacter pylori is one of the agents associated with gastric cancer and has high prevalence in developing countries. Its routes of transmission have not been fully established, however, some studies have detected H. pylori DNA in wastewater, groundwater and surface water. The aim of our study was detect H. pylori DNA in water samples from rural water supplies of San Cristóbal and the Tachira’s Regional Water Supply (TRWS). Materials and methods: Water (500 ml) of six rural water supplies and the TRWS were collected. T DNA of Helicobacter genus was detected by Polimerase Chain Reaction (PCR) and seminested PCR and the PCR amplicons were sequenced. Results: Helicobacter genus PCR results were negative but the seminested PCR were positive in three samples. However the two amplicons sequenced showed a 99% similitud with Ralstonia pickettii. Conclusions: Helicobacter amplicon sequenced, showed a high similarity with R. pickettii, an oportunist pathogen, with similar characteristics to H. pylori.

Modelo de evaluación integral para la educación en el trabajo del internado de Estomatología / Model of comprehensive assessment for the in-service training in the odontoloy internship

Fundamento: la evaluación sistemática de estudiantes durante la educación en el trabajo es imprescindible para valorar el cumplimiento de las habilidades alcanzadas. Objetivo: valorar el efecto de un modelo de evaluación integral diseñado para el internado de Estomatología a través de criterios de especialistas y la calidad de resultados académicos. Métodos: se realizó una investigación cualitativa, de tipo experimental, en la Facultad de Estomatología de Villa Clara, en el curso escolar 2013-2014. El universo lo constituyeron 180 estudiantes de quinto año, con los cuales se trabajó en su totalidad; se utilizaron métodos teóricos y entre los empíricos: revisión documental, la encuesta y la técnica de grupo nominal. Resultados: en la revisión documental realizada se constató la necesidad de un modelo de evaluación integral para el control y evaluación sistemático en la educación en el trabajo del interno de Estomatología, el cual fue diseñado incluyendo en él, todas las acciones que responden a objetivos instructivos y formativos de los programas. Conclusiones: el instrumento fue valorado como pertinente por resultar necesario, útil, factible, económico y de fácil manipulación, estimuló la creatividad metodológica del colectivo de año y contribuyó al perfeccionamiento del proceso docente educativo al exhibir resultados de calidad luego de su implementación.

Background: the systematic evaluation of students during the in-service training is indispensable to value the abilities acquisition. Objective: to value the effect of the comprehensive assessment model designed for the Odontoloy internship through the specialists' criteria and the quality of academic results. Methods: it was carried out a qualitative investigation, of experimental type, in Villa Clara Odontoloy faculty, in the academic year 2013-2014. The universe comprised 180 fifth year students, the sample matches the universe; theoretical methods were used and among the empiric ones: documental revision, the survey and the technique of nominal group. Results: the documental revision showed the necessity of a comprehensive assessment model for the control and systematic evaluation in the in-service training of the Odontoloy internship, which was designed including in it all the actions that respond to instructive and formative objectives of the programs. Conclusions: the assessment instrument was valued as pertinent for it was necessary, useful, feasible, economic and of easy manipulation, it stimulated the methodological creativity of the year teaching staff and it contributed to the improvement of the teaching-learning process because it showed good quality results after it had been implemented.

Environmental scanning electron microscopy analysis of Proteus mirabilis biofilms grown on chitin and stainless steel.

Proteus mirabilis is a human pathogen able to form biofilms on the surface of urinary catheters. Little is known about P. mirabilis biofilms on natural or industrial surfaces and the potential consequences for these settings. The main aim of this work was to assess and compare the adhesion and biofilm formation of P. mirabilis strains from different origins on chitin and stainless steel surfaces within 4 to 96 h. Using environmental scanning electron microscopy, the biofilms of a clinical strain grown on chitin at 4 h showed greater adhesion, aggregation, thickness, and extracellular matrix production than those grown on stainless steel, whereas biofilms of an environmental strain had less aggregation on both surfaces. Biofilms of both P. mirabilis strains developed different structures on chitin, such as pillars, mushrooms, channels, and crystalline-like precipitates between 24 and 96 h, in contrast with flat-layer biofilms produced on stainless steel. Significant differences (p < 0.05) were found in the frequency of pillars and channels. Images of transmission electron microscopy demonstrated abundant fimbriae in 100 % of cells from both strains, which could be related to surface adherence and biofilm formation. This represents the first study of P. mirabilis showing adhesion, biofilm formation, and development of different structures on surfaces found outside the human host.

A Point Mutation in PDGFRB Causes Autosomal-Dominant Penttinen Syndrome.

Penttinen syndrome is a distinctive disorder characterized by a prematurely aged appearance with lipoatrophy, epidermal and dermal atrophy along with hypertrophic lesions that resemble scars, thin hair, proptosis, underdeveloped cheekbones, and marked acro-osteolysis. All individuals have been simplex cases. Exome sequencing of an affected individual identified a de novo c.1994T>C p.Val665Ala variant in PDGFRB, which encodes the platelet-derived growth factor receptor ß. Three additional unrelated individuals with this condition were shown to have the identical variant in PDGFRB. Distinct mutations in PDGFRB have been shown to cause infantile myofibromatosis, idiopathic basal ganglia calcification, and an overgrowth disorder with dysmorphic facies and psychosis, none of which overlaps with the clinical findings in Penttinen syndrome. We evaluated the functional consequence of this causative variant on the PDGFRB signaling pathway by transfecting mutant and wild-type cDNA into HeLa cells, and transfection showed ligand-independent constitutive signaling through STAT3 and PLCγ. Penttinen syndrome is a clinically distinct genetic condition caused by a PDGFRB gain-of-function mutation that is associated with a specific and unusual perturbation of receptor function.