VESPA: an optimized protocol for accurate metabarcoding-based characterization of vertebrate eukaryotic endosymbiont and parasite assemblages.

Protocols for characterizing taxonomic assemblages by deep sequencing of short DNA barcode regions (metabarcoding) have revolutionized our understanding of microbial communities and are standardized for bacteria, archaea, and fungi. Unfortunately, comparable methods for host-associated eukaryotes have lagged due to technical challenges. Despite 54 published studies, issues remain with primer complementarity, off-target amplification, and lack of external validation. Here, we present VESPA (Vertebrate Eukaryotic endoSymbiont and Parasite Analysis) primers and optimized metabarcoding protocol for host-associated eukaryotic community analysis. Using in silico prediction, panel PCR, engineered mock community standards, and clinical samples, we demonstrate VESPA to be more effective at resolving host-associated eukaryotic assemblages than previously published methods and to minimize off-target amplification. When applied to human and non-human primate samples, VESPA enables reconstruction of host-associated eukaryotic endosymbiont communities more accurately and at finer taxonomic resolution than microscopy. VESPA has the potential to advance basic and translational science on vertebrate eukaryotic endosymbiont communities, similar to achievements made for bacterial, archaeal, and fungal microbiomes.

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.

The multi-tissue landscape of somatic mtDNA mutations indicates tissue-specific accumulation and removal in aging.

Accumulation of somatic mutations in the mitochondrial genome (mtDNA) has long been proposed as a possible mechanism of mitochondrial and tissue dysfunction that occurs during aging. A thorough characterization of age-associated mtDNA somatic mutations has been hampered by the limited ability to detect low-frequency mutations. Here, we used Duplex Sequencing on eight tissues of an aged mouse cohort to detect >89,000 independent somatic mtDNA mutations and show significant tissue-specific increases during aging across all tissues examined which did not correlate with mitochondrial content and tissue function. G→A/C→T substitutions, indicative of replication errors and/or cytidine deamination, were the predominant mutation type across all tissues and increased with age, whereas G→T/C→A substitutions, indicative of oxidative damage, were the second most common mutation type, but did not increase with age regardless of tissue. We also show that clonal expansions of mtDNA mutations with age is tissue- and mutation type-dependent. Unexpectedly, mutations associated with oxidative damage rarely formed clones in any tissue and were significantly reduced in the hearts and kidneys of aged mice treated at late age with elamipretide or nicotinamide mononucleotide. Thus, the lack of accumulation of oxidative damage-linked mutations with age suggests a life-long dynamic clearance of either the oxidative lesions or mtDNA genomes harboring oxidative damage.

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.

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

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.

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.

Pediatric Inflammatory Bowel Disease: A Multicenter Study of Changing Trends in Argentina Over the Past 30 Years.

Purpose: To analyze the characteristics of pediatric inflammatory bowel disease (IBD) over the past three decades in Argentina and determine if there are differences between the first two decades and the past decade. Methods: We conducted a retrospective multicenter analytical study in children with IBD between 0 and 18 years of age diagnosed between 1987 and 2017 in three tertiary health centers in Argentina. The evaluation included clinical characterization, endoscopy, histology, and imaging data together with therapeutic strategies. The patients were divided into two groups: Group 1, diagnosed between 1987 and 2007, and Group 2, diagnosed between 2008 and 2017. Results: Of the 756 patients included, 409 (54%) had ulcerative colitis (UC), 250 (33%) had Crohn's disease (CD), and 97 (13%) had IBD-unclassified (IBD-U). The positive family history was 3.8%, which was more frequent among children under two years of age (6.7%). There were no significant differences in clinical presentation and extraintestinal manifestations between periods, with hepatic manifestations being the most frequent. In the last decade, we found an upward trend in CD, a downward trend in UC/IBD-U, even after adjustment for socioeconomic status, and a decrease of 50% in surgical treatments coinciding with the advent of biological therapy. Conclusion: This is the first multicenter cohort study in a Latin American country to describe clinical, endoscopic, and therapeutic data across the past 30-year period. Although CD was responsible for the overall increase in incidence, UC was still prevalent in this region.

The Complicated Nature of Somatic mtDNA Mutations in Aging.

Mitochondria are the main source of energy used to maintain cellular homeostasis. This aspect of mitochondrial biology underlies their putative role in age-associated tissue dysfunction. Proper functioning of the electron transport chain (ETC), which is partially encoded by the extra-nuclear mitochondrial genome (mtDNA), is key to maintaining this energy production. The acquisition of de novo somatic mutations that interrupt the function of the ETC have long been associated with aging and common diseases of the elderly. Yet, despite over 30 years of study, the exact role(s) mtDNA mutations play in driving aging and its associated pathologies remains under considerable debate. Furthermore, even fundamental aspects of age-related mtDNA mutagenesis, such as when mutations arise during aging, where and how often they occur across tissues, and the specific mechanisms that give rise to them, remain poorly understood. In this review, we address the current understanding of the somatic mtDNA mutations, with an emphasis of when, where, and how these mutations arise during aging. Additionally, we highlight current limitations in our knowledge and critically evaluate the controversies stemming from these limitations. Lastly, we highlight new and emerging technologies that offer potential ways forward in increasing our understanding of somatic mtDNA mutagenesis in the aging process.

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)

A replication-linked mutational gradient drives somatic mutation accumulation and influences germline polymorphisms and genome composition in mitochondrial DNA.

Mutations in mitochondrial DNA (mtDNA) cause maternally inherited diseases, while somatic mutations are linked to common diseases of aging. Although mtDNA mutations impact health, the processes that give rise to them are under considerable debate. To investigate the mechanism by which de novo mutations arise, we analyzed the distribution of naturally occurring somatic mutations across the mouse and human mtDNA obtained by Duplex Sequencing. We observe distinct mutational gradients in G→A and T→C transitions delimited by the light-strand origin and the mitochondrial Control Region (mCR). The gradient increases unequally across the mtDNA with age and is lost in the absence of DNA polymerase γ proofreading activity. In addition, high-resolution analysis of the mCR shows that important regulatory elements exhibit considerable variability in mutation frequency, consistent with them being mutational 'hot-spots' or 'cold-spots'. Collectively, these patterns support genome replication via a deamination prone asymmetric strand-displacement mechanism as the fundamental driver of mutagenesis in mammalian DNA. Moreover, the distribution of mtDNA single nucleotide polymorphisms in humans and the distribution of bases in the mtDNA across vertebrate species mirror this gradient, indicating that replication-linked mutations are likely the primary source of inherited polymorphisms that, over evolutionary timescales, influences genome composition during speciation.

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

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.

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

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: 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.

Real-time PCR detection of a 16S rRNA single mutation of Helicobacter pylori isolates associated with reduced susceptibility and resistance to tetracycline in the gastroesophageal mucosa of individual hosts.

The molecular mechanism of Helicobacter pylori resistance to tetracycline involves mutations in the primary binding site of the ribosome. A resistance or reduced susceptibility to tetracycline could be the result of single, double or triple mutations in the 16S rRNA gene of H. pylori. We investigated if the genotype was correlated to tetracycline resistance as determined phenotypically in vitro for 96 H. pylori isolates in the gastroesophageal mucosa of Venezuelan individual hosts. E-test for antimicrobial susceptibility test and real-time PCR for the detection of 16S rRNA gene mutations were performed in 96 H. pylori isolates (48 obtained from antrum, and 48 from oesophagus) from eight dyspeptic patients. In the gastric mucosa, 38 isolates were identified sensitive and 10 resistant to tetracycline by E-test, whereas 44 sensitive and 4 resistant isolates were found in the oesophagus. Real-time PCR detection of the 16S rRNA gene exhibited mutants with a single base-pair substitution (AGA926GGA) in six antrum isolates and seven oesophagus isolates, whereas only three harboured a low level of tetracycline resistance in vitro. Our results indicate that real-time PCR detection of 16S rRNA is a reliable method to classify among tetracycline-resistant genotypes and useful in patients who have experienced a first-line treatment failure with triple therapy.

Comparative prevalence of Oxalobacter formigenes in three human populations.

There has been increasing interest in the human anaerobic colonic bacterium Oxalobacter formigenes because of its ability to metabolize oxalate, and its potential contribution to protection from calcium oxalate kidney stones. Prior studies examining the prevalence of this organism have focused on subjects in developed countries and on adults. Now using O. formigenes-specific PCR, we have compared the prevalence of these organisms among subjects in two remote areas in which modern medical practices have hardly been present with a USA group of mothers and their infants for the first three years of life. Among the Amerindians of the Yanomami-Sanema and Yekwana ethnic groups in Venezuela and the Hadza in Tanzania, O. formigenes was detected in 60-80% of the adult subjects, higher than found in adults from USA in this and prior studies. In young children, the prevalence was much lower in USA than in either tribal village. These data extend our understanding of the epidemiology of O. formigenes carriage, and are consistent with the hypothesis that the rising incidence of kidney stones is associated with the progressive loss of O. formigenes colonization in populations that have been highly impacted by modern medical practices.

Publisher Correction: Complex virome in feces from Amerindian children in isolated Amazonian villages.

In the original version of this Article, the affiliation details for Eric Delwart were incorrectly given as 'Blood Systems Research Institute, San Francisco, CA 94118, USA and Amazonic Center for Research and Control of Tropical Diseases (CAICET), Puerto Ayacucho 7101, Venezuela'. The correct affiliations are 'Blood Systems Research Institute, San Francisco, CA 94118, USA and Department of Laboratory Medicine, University of California at San Francisco, San Francisco, CA 94118, USA'. This has been corrected in both the PDF and HTML versions of the Article.

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.

Complex virome in feces from Amerindian children in isolated Amazonian villages.

The number of viruses circulating in small isolated human populations may be reduced by viral extinctions and rare introductions. Here we used viral metagenomics to characterize the eukaryotic virome in feces from healthy children from a large urban center and from three Amerindian villages with minimal outside contact. Numerous human enteric viruses, mainly from the Picornaviridae and Caliciviridae families, were sequenced from each of the sites. Multiple children from the same villages shed closely related viruses reflecting frequent transmission clusters. Feces of isolated villagers also contained multiple viral genomes of unknown cellular origin from the Picornavirales order and CRESS-DNA group and higher levels of nematode and protozoan DNA. Despite cultural and geographic isolation, the diversity of enteric human viruses was therefore not reduced in these Amazonian villages. Frequent viral introductions and/or increased susceptibility to enteric infections may account for the complex fecal virome of Amerindian children in isolated villages.