Dysbiosis by Eradication of Helicobacter pylori Infection Associated with Follicular Gastropathy and Pangastropathy.

Dysbiosis plays an important role in the development of bacterial infections in the gastric mucosa, particularly Helicobacter pylori. The international guidelines for the treatment of H. pylori infections suggest standard triple therapy (STT). Nevertheless, because of the increasing resistance rates to clarithromycin, metronidazole has been widely considered in several countries. Unfortunately, the non-justified administration of antibiotics induces dysbiosis in the target organ. We characterized the gastric microbiota of patients diagnosed with follicular gastropathy and pangastropathy attributed to H. pylori infection, before and after the administration of STT with metronidazole. Dominant relative abundances of Cutibacterium were observed in pre-treatment patients, whereas H. pylori was observed at <11%, suggesting the multifactor property of the disease. The correlation of Cutibacterium acnes and H. pylori with gastric infectious diseases was also evaluated using quantitative real-time polymerase chain reaction. The dominance of C. acnes over H. pylori was observed in gastritis, gastropathies, and non-significant histological alterations. None of the microorganisms were detected in the intestinal metaplasia. Post-treatment alterations revealed an increase in the relative abundances of Staphylococcus, Pseudomonas, and Klebsiella. Non-H. pylori gastrointestinal bacteria can be associated with the initiation and development of gastric diseases, such as pathobiont C. acnes.

Is Your Kid Actin Out? A Series of Six Patients With Inherited Actin-Related Protein 2/3 Complex Subunit 1B Deficiency and Review of the Literature.

BACKGROUND: Hereditary actin-related protein 2/3 complex subunit 1B deficiency is characterized clinically by ear, skin, and lung infections, bleeding, eczema, food allergy, asthma, skin vasculitis, colitis, arthritis, short stature, and lymphadenopathy. OBJECTIVE: We aimed to describe the clinical, laboratory, and genetic features of six patients from four Mexican families. METHODS: We performed exome sequencing in patients of four families with suspected actinopathy, collected their data from medical records, and reviewed the literature for reports of other patients with actin-related protein 2/3 complex subunit 1B deficiency. RESULTS: Six patients from four families were included. All had recurrent infections, mainly bacterial pneumonia, and cellulitis. A total of 67% had eczema whereas 50% had food allergies, failure to thrive, hepatomegaly, and bleeding. Eosinophilia was found in all; 84% had thrombocytopenia, 67% had abnormal-size platelets and anemia. Serum levels of IgG, IgA, and IgE were highly increased in most; IgM was normal or low. T cells were decreased in 67% of patients, whereas B and NK cells were increased in half of patients. Two of the four probands had compound heterozygous variants. One patient was successfully transplanted. We identified 28 other patients whose most prevalent features were eczema, recurrent infections, failure to thrive, bleeding, diarrhea, allergies, vasculitis, eosinophilia, platelet abnormalities, high IgE/IgA, low T cells, and high B cells. CONCLUSION: Actin-related protein 2/3 complex subunit 1B deficiency has a variable and heterogeneous clinical spectrum, expanded by these cases to include keloid scars and Epstein-Barr virus chronic hepatitis. A novel deletion in exon 8 was shared by three unrelated families and might be the result of a founder effect.

Peutz-Jeghers syndrome in pediatric patients: experience in a tertiary care institution in Mexico.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant inherited disease characterized by the development of polyps in the gastrointestinal tract, mucocutaneous pigmentation, and the risk of developing malignant neoplasms. This study aimed to analyze the epidemiological, clinical, and histopathological data of patients with PJS treated in a tertiary pediatric hospital. METHODS: We conducted a retrospective observational study to describe the epidemiological, clinical, endoscopic, and histological characterization of patients with PJS treated in a tertiary pediatric hospital in Mexico. RESULTS: We included 13 cases with a male-female ratio of 1.16:1. Abdominal pain was the main reason for consultation, followed by rectorrhagia. Patients showed mucocutaneous pigmentation and polyps in the gastrointestinal tract, frequently of the hamartomatous type, although inflammatory polyps, follicular hyperplasia, and adenomatous polyps were also found. Among the complications, there was a high prevalence of emergency surgery secondary to abdominal obstructive processes, the main reason for first-time consultation in these patients. CONCLUSIONS: The main clinical manifestations were mucocutaneous pigmentation, abdominal pain, and rectorrhagia. PJS should be included in the differential diagnosis in the presence of intestinal obstruction. The diagnosis of PJS should not be excluded if hamartomatous polyps are not evident on the first endoscopy. Nutritional assessment should be included due to the risk of presenting some degree of malnutrition.

INTRODUCCIÓN: El síndrome de Peutz-Jeghers es una enfermedad hereditaria autosómica dominante poco frecuente, caracterizada por el desarrollo de pólipos en el tubo digestivo, pigmentación mucocutánea y riesgo de desarrollar neoplasias malignas. El objetivo de este estudio fue analizar los datos epidemiológicos, clínicos e histopatológicos de los pacientes con SPJ atendidos en un hospital pediátrico de tercer nivel. MÉTODOS: Se llevó a cabo un estudio observacional retrospectivo, para describir las características epidemiológicas, clínicas, endoscópicas e histopatológicas de los pacientes con SPJ atendidos en un hospital pediátrico de tercer nivel de atención en México. RESULTADOS: Se recopilaron 13 casos con una relación masculino-femenino de 1.16:1. El dolor abdominal fue el principal motivo de consulta, seguido por rectorragia. Los pacientes presentaban pigmentación mucocutánea y pólipos en el tubo digestivo, la mayoría del tipo hamartomatoso, aunque también se hallaron pólipos inflamatorios, hiperplasia folicular y adenomatosos. Dentro de las complicaciones se encontró una alta prevalencia de cirugías de emergencia secundarias a procesos obstructivos abdominales, motivo principal de consulta de primera vez en estos pacientes. CONCLUSIONES: Las principales manifestaciones clínicas fueron pigmentación mucocutánea, dolor abdominal y rectorragia. Ante un cuadro de obstrucción intestinal se debe considerar el SPJ en el diagnóstico diferencial. No se debe excluir el diagnóstico de SPJ si no se evidencian pólipos hamartomatosos en la primera endoscopia. Se debe incluir la valoración nutricional por el riesgo de presentar algún grado de desnutrición.

Ganglioneuromatosis intestinal difusa a lo largo del tubo digestivo.

BACKGROUND: Ganglioneuromas are histologically benign neoplasms derived from the sympathetic nervous system, whose occurrence in the gastrointestinal tract is rare and often syndromic. According to the injury pattern and extension, lesions are divided into polypoid ganglioneuroma, ganglioneuromatous polyposis, and diffuse ganglioneuromatosis. This work aimed to present the incidental post mortem finding of diffuse ganglioneuromatosis of the gastrointestinal tract in a patient without syndromic involvement. CASE REPORT: We describe the case of a two-year-old female patient with surgically corrected type III tracheoesophageal atresia and fistulous recanalization, multiple episodes of aspiration pneumonia, and septic shock. During the last admission, she developed massive pulmonary hemorrhage and multi-organ failure. Post mortem histopathological study identified hypertrophy of the pylorus and enlarged enteric nerve trunks and plexuses with intermingled mature ganglion cells. We identified ganglioneuromatosis affecting all gastrointestinal tract segments with the predominance of the myenteric plexuses. CONCLUSIONS: Intestinal ganglioneuromatosis is a rare disease with a spectrum of lesions ranging from isolated to syndromic with high morbidity and mortality. Therefore, it is necessary to know the condition, investigate systematically when it is suspected, and rely on genetic studies to confirm or rule out any syndromic association.

INTRODUCCIÓN: Los ganglioneuromas son neoplasias histológicamente benignas derivadas del sistema nervioso simpático, cuya ocurrencia en el tubo digestivo es rara y comúnmente sindromática. De acuerdo con el patrón de la lesión y la extensión se dividen en ganglioneuroma polipoide, poliposis ganglioneuromatosa y ganglioneuromatosis difusa. El objetivo de este trabajo es presentar el hallazgo incidental post mortem de ganglioneuromatosis difusa del tubo digestivo en una paciente sin afectación sindromática. CASO CLÍNICO: Se describe el caso de un paciente de sexo femenino de 2 años con atresia traqueoesofágica tipo III corregida quirúrgicamente que cursó con recanalización fistulosa, múltiples episodios de neumonía por aspiración y choque séptico. Durante el último ingreso cursó con hemorragia pulmonar masiva y falla multiorgánica. En el estudio post mortem se identificó hipertrofia del píloro y de los troncos y plexos nerviosos entéricos con células ganglionares maduras entremezcladas. Se identificó ganglioneuromatosis que afectaba todos los segmentos del tubo digestivo, con predominio de los plexos mientéricos. CONCLUSIONES: La ganglioneuromatosis intestinal es una rara enfermedad que presenta un espectro de lesiones desde una forma aislada hasta sindromática con morbimortalidad elevada. Por ello, es necesario conocer la enfermedad, indagar sistemáticamente cuando se sospeche y apoyarse de estudios genéticos que confirmen o descarten alguna asociación sindromática.

Peutz-Jeghers syndrome in pediatric patients: experience in a tertiary care institution in Mexico / Síndrome de Peutz-Jeghers en pacientes pediátricos: experiencia en una institución de tercer nivel de atención en México

Abstract Background: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant inherited disease characterized by the development of polyps in the gastrointestinal tract, mucocutaneous pigmentation, and the risk of developing malignant neoplasms. This study aimed to analyze the epidemiological, clinical, and histopathological data of patients with PJS treated in a tertiary pediatric hospital. Methods: We conducted a retrospective observational study to describe the epidemiological, clinical, endoscopic, and histological characterization of patients with PJS treated in a tertiary pediatric hospital in Mexico. Results: We included 13 cases with a male-female ratio of 1.16:1. Abdominal pain was the main reason for consultation, followed by rectorrhagia. Patients showed mucocutaneous pigmentation and polyps in the gastrointestinal tract, frequently of the hamartomatous type, although inflammatory polyps, follicular hyperplasia, and adenomatous polyps were also found. Among the complications, there was a high prevalence of emergency surgery secondary to abdominal obstructive processes, the main reason for first-time consultation in these patients. Conclusions: The main clinical manifestations were mucocutaneous pigmentation, abdominal pain, and rectorrhagia. PJS should be included in the differential diagnosis in the presence of intestinal obstruction. The diagnosis of PJS should not be excluded if hamartomatous polyps are not evident on the first endoscopy. Nutritional assessment should be included due to the risk of presenting some degree of malnutrition.

Resumen Introducción: El síndrome de Peutz-Jeghers es una enfermedad hereditaria autosómica dominante poco frecuente, caracterizada por el desarrollo de pólipos en el tubo digestivo, pigmentación mucocutánea y riesgo de desarrollar neoplasias malignas. El objetivo de este estudio fue analizar los datos epidemiológicos, clínicos e histopatológicos de los pacientes con SPJ atendidos en un hospital pediátrico de tercer nivel. Métodos: Se llevó a cabo un estudio observacional retrospectivo, para describir las características epidemiológicas, clínicas, endoscópicas e histopatológicas de los pacientes con SPJ atendidos en un hospital pediátrico de tercer nivel de atención en México. Resultados: Se recopilaron 13 casos con una relación masculino-femenino de 1.16:1. El dolor abdominal fue el principal motivo de consulta, seguido por rectorragia. Los pacientes presentaban pigmentación mucocutánea y pólipos en el tubo digestivo, la mayoría del tipo hamartomatoso, aunque también se hallaron pólipos inflamatorios, hiperplasia folicular y adenomatosos. Dentro de las complicaciones se encontró una alta prevalencia de cirugías de emergencia secundarias a procesos obstructivos abdominales, motivo principal de consulta de primera vez en estos pacientes. Conclusiones: Las principales manifestaciones clínicas fueron pigmentación mucocutánea, dolor abdominal y rectorragia. Ante un cuadro de obstrucción intestinal se debe considerar el SPJ en el diagnóstico diferencial. No se debe excluir el diagnóstico de SPJ si no se evidencian pólipos hamartomatosos en la primera endoscopia. Se debe incluir la valoración nutricional por el riesgo de presentar algún grado de desnutrición.

Ganglioneuromatosis intestinal difusa a lo largo del tubo digestivo / Diffuse intestinal ganglioneuromatosis along the gastrointestinal tract

Resumen Introducción: Los ganglioneuromas son neoplasias histológicamente benignas derivadas del sistema nervioso simpático, cuya ocurrencia en el tubo digestivo es rara y comúnmente sindromática. De acuerdo con el patrón de la lesión y la extensión se dividen en ganglioneuroma polipoide, poliposis ganglioneuromatosa y ganglioneuromatosis difusa. El objetivo de este trabajo es presentar el hallazgo incidental post mortem de ganglioneuromatosis difusa del tubo digestivo en una paciente sin afectación sindromática. Caso clínico: Se describe el caso de un paciente de sexo femenino de 2 años con atresia traqueoesofágica tipo III corregida quirúrgicamente que cursó con recanalización fistulosa, múltiples episodios de neumonía por aspiración y choque séptico. Durante el último ingreso cursó con hemorragia pulmonar masiva y falla multiorgánica. En el estudio post mortem se identificó hipertrofia del píloro y de los troncos y plexos nerviosos entéricos con células ganglionares maduras entremezcladas. Se identificó ganglioneuromatosis que afectaba todos los segmentos del tubo digestivo, con predominio de los plexos mientéricos. Conclusiones: La ganglioneuromatosis intestinal es una rara enfermedad que presenta un espectro de lesiones desde una forma aislada hasta sindromática con morbimortalidad elevada. Por ello, es necesario conocer la enfermedad, indagar sistemáticamente cuando se sospeche y apoyarse de estudios genéticos que confirmen o descarten alguna asociación sindromática.

Abstract Background: Ganglioneuromas are histologically benign neoplasms derived from the sympathetic nervous system, whose occurrence in the gastrointestinal tract is rare and often syndromic. According to the injury pattern and extension, lesions are divided into polypoid ganglioneuroma, ganglioneuromatous polyposis, and diffuse ganglioneuromatosis. This work aimed to present the incidental post mortem finding of diffuse ganglioneuromatosis of the gastrointestinal tract in a patient without syndromic involvement. Case report: We describe the case of a two-year-old female patient with surgically corrected type III tracheoesophageal atresia and fistulous recanalization, multiple episodes of aspiration pneumonia, and septic shock. During the last admission, she developed massive pulmonary hemorrhage and multi-organ failure. Post mortem histopathological study identified hypertrophy of the pylorus and enlarged enteric nerve trunks and plexuses with intermingled mature ganglion cells. We identified ganglioneuromatosis affecting all gastrointestinal tract segments with the predominance of the myenteric plexuses. Conclusions: Intestinal ganglioneuromatosis is a rare disease with a spectrum of lesions ranging from isolated to syndromic with high morbidity and mortality. Therefore, it is necessary to know the condition, investigate systematically when it is suspected, and rely on genetic studies to confirm or rule out any syndromic association.

The interplay between estrogen receptor beta and protein kinase C, a crucial collaboration for medulloblastoma cell proliferation and invasion.

Medulloblastoma (MB) is the most common and aggressive pediatric intracranial tumor. Estrogen receptor ß (ERß) expression correlates with MB development and its phosphorylation modifies its transcriptional activity in a ligand-dependent or independent manner. Using in silico tools, we have identified several residues in ERß protein as potential targets of protein kinases C (PKCs) α and δ. Using Daoy cells, we observed that PKCα and PKCδ associate with ERß and induce its phosphorylation. The activation of ERß promotes MB cells proliferation and invasion, and PKCs downregulation dysregulates these steroid receptor mediated processes. Our data suggest that these kinases may play a crucial role in the regulation of the ERß transcriptional activity. Overexpression of both PKCα and PKCδ in MB biopsies samples supports their relevance in MB progression.

Histomorphometry evaluation of bone anabolism promoted by prostaglandin E1 and its relation to hypercalcemia / Evaluación histomorfométrica del anabolismo óseo en la reparación promovida por la prostaglandina E1 y su relación con la hipercalcemia

Abstract Background: At present, parathyroid hormone is the only existing anabolic bone therapy but produces hypercalcemia. Prostaglandin E1 (PGE1) has been suggested as a bone anabolic agent that allows bone modeling formation without producing hypercalcemia. This study aimed to corroborate these PGE1 properties. Methods: For 22 days, rabbits (n = 30) were divided into three groups (n = 10 each group) and received intravenous solutions: vehicle (control group), palate disjunction + vehicle (sham group), and palate disjunction + 50 mg of PGE1 (PGE1 group). On days 1, 3, and 22, palatine suture X-rays were taken. On day 22, bone formation markers were analyzed, and the rabbits were sacrificed. Bone palate undecalcified samples were processed. Histomorphometry software was used to analyze bone parameters, and the mineralization front was stained with toluidine blue. Scalloped lines reflect remodeling-based bone formation (RBF), and smooth lines reflect modeling-based formation (MBF). Results: X-rays showed more significant palatal disjunction in the PGE1 group; this group exhibited significant calcitriol serum increments. Hypercalciuria was observed in the PGE1 group, and resorption markers (N-telopeptides) remained stable. Sutural bones in the PGE1 group exhibited significant anabolism in structural parameters. RBF was 20%, and MBF was 6% in the sham group; in the PGE1 group, RBF was 8.6%, and MBF was 17%. In the PGE1 group, mineralization was significantly accelerated, but resorption remained stable. Conclusions: This model suggests that PGE1 favors palate disjunction, calcitriol synthesis, and shortens the mineralization. Therefore, PGE1 is an important bone anabolic molecule predominantly of modeling-based form and no hypercalcemia.

Resumen Introducción: La hormona paratiroidea es la única molécula anabólica ósea, pero ocasiona hipercalcemia. La prostaglandina E1 (PGE1) sugiere ser un anabólico óseo con formación por modelación predominante y generalmente no ocasiona hipercalcemia. El objetivo de este estudio fue corroborar estas propiedades de la PGE1. Métodos: Por 22 días, 30 conejos divididos en tres grupos (n = 10 cada grupo) recibieron una solución por vía intravenosa: vehículo (grupo control), disyunción palatina más vehículo (grupo sham) y disyunción palatina más 50 mg de PGE1 (grupo PGE1). A los días 1, 3 y 22 se obtuvieron radiografías de la sutura palatina. En el día 22 se analizaron los marcadores bioquímicos de formación ósea y se sacrificó a los conejos. Las suturas y los huesos suturales se procesaron sin descalcificar. La evaluación histomorfométrica fue digitalizada y el frente de mineralización ósea se tiñó con azul de toluidina. Las líneas irregulares reflejan resorción (remodelación) y las líneas rectas no resorción (modelación). Resultados: Radiográficamente, la disyunción palatina fue mayor en el grupo PGE1. Este grupo mostró una hipercalcitonemia significativa, pero la calcemia y los marcadores resortivos (N-telopéptidos) se mantuvieron estables. Por histomorfometría, los huesos suturales del grupo PGE1 mostraron anabolismo significativo en parámetros estructurales. En el grupo sham, la remodelación ósea fue del 20% y la modelación fue del 6%; en el grupo PGE1, la remodelación fue del 8.6% y la modelación fue del 17%. En este mismo grupo, la mineralización fue significativamente acelerada, pero la resorción se mantuvo igual. Conclusiones: Este modelo sugiere que la PGE1 favorece la disyunción palatina y el aumento del calcitriol, y acelera la mineralización y el anabolismo óseo por modelación predominante sin hipercalcemia.

Curli of Uropathogenic Escherichia coli Enhance Urinary Tract Colonization as a Fitness Factor.

Curli, a type of fimbriae widely distributed in uropathogenic Escherichia coli (UPEC), are involved in adhesion to human bladder cell surfaces and biofilm development. The role of UPEC curli was evaluated in a murine model of urinary tract infection. The aim of this study was to establish the role of curli in C57BL/6 mice transurethrally infected with curli-producing and non-curli-producing UPEC strains. We confirmed that curli enhanced UPEC colonization in the urinary tract, resulting in damage to both the bladder and kidney. Intranasal immunization with recombinant CsgA protein protected against colonization by curli-producing UPEC in the urinary tract. Quantification of cytokines from urinary tract organs showed increases in interleukin-6 and tumor necrosis factor (TNF) release in the kidneys 48 h postinfection with curli-producing UPEC. By contrast, mice infected with non-curli-producing UPEC showed the highest release of interleukin-6, -10, and -17A and TNF. Curli may obscure other fimbriae and LPS, preventing interactions with Toll-like receptors. When intranasal immunization with recombinant FimH and PapG proteins and subsequent infection with this strain were performed, cytokine quantification showed a decrease in the stimulation and release by the uroepithelium. Thus, curli are amyloid-like fimbriae that enhances colonization in the urinary tract and a possible fitness factor.

Differential expression of miRNA-146a and miRNA-155 in gastritis induced by Helicobacter pylori infection in paediatric patients, adults, and an animal model.

BACKGROUND: Helicobacter pylori is a major aetiologic agent associated with gastritis. H. pylori infections increase the expression of the Toll-like receptor (TLR), which in turn modulates the expression of microRNA (miRNA)-146a and miRNA-155. The objective of this study was to compare the expression of miRNA-146a and miRNA-155 in gastric lesions of paediatric and adult patients with different pathologies and in Mongolian gerbils (Meriones unguiculatus) infected with H. pylori 26,695. METHODS: Quantification of miRNA expression was performed by quantitative real-time polymerase chain reaction (qRT-PCR) of paraffin-embedded gastric lesions of children with or without an infection (n = 25), adults with follicular gastritis and metaplasia (n = 32) and eight-week-old M. unguiculatus males (Hsd:MON) infected with H. pylori 26,695 for 0, 3, 6, 12 and 18 months (n = 25). The genes RNU48 and RNU6 were used as endogenous controls for data normalization. Statistical analyses were performed using Kruskal-Wallis, Mann-Whitney, ANOVA and Student's t-test. RESULTS: The expression of miRNA-146a and miRNA-155 in infected children increased by 247.6- and 79.4-fold (on average), respectively, compared to that observed in the control group. However, these results were not significant (p = 0.12 and p = 0.07 respectively). In some children a gradual increase in expression was observed, while in others, expression was very high. Additionally, the expression levels of miRNA-146a and miRNA-155 increased by an average of 21.7- and 62-fold, respectively, in adult patients with follicular gastritis when compared to those of the controls. In M. unguiculatus infected with H. pylori 26,695, the expression of both miRNAs increased as the infection progressed. CONCLUSION: This is the first report to show differences in the expression of miRNA-146a and miRNA-155 in paediatric and adult patients with gastritis who were infected with H. pylori. In addition, in M. unguiculatus infected with H. pylori, miRNA expression was associated with the progression of infection and the ability of the bacteria to adapt to the host.

Oral primary localized amyloidosis in HIV-infected patients: the oral face of a described skin lesion.

Oral primary localized amyloidosis should be considered in the diagnosis of oral white lesions such as hyperplastic candidosis, lichen planus and lichenoid reactions; it is not associated with antiretroviral therapy use, systemic involvement or malignant transformation.

Análisis in silico de proteínas potencialmente involucradas en la biogénesis de fimbrias en Helicobacter pylori / In silico analysis of proteins potentially involved in fimbrial biogenesis in Helicobacter pylori

Introducción. La colonización e infección crónica por Helicobacter pylori es el factor de mayor contribución al desarrollo de cáncer gástrico. Se ha descrito un gran repertorio de adhesinas que contribuyen a la adaptación específica de la bacteria al nicho gástrico y, para H. pylori , al igual que en otras bacterias patógenas, la formación de biopelícula es fundamental en la supervivencia a ambientes no favorables. Las fimbrias o pili tipo IV son responsables de la adhesión de diversas bacterias patógenas ( Escherichia coli , Pseudomonas aeruginosa y Vibrio cholerae) a distintas superficies. El objetivo de este trabajo fue identificar y analizar genes que pudieran codificar para proteínas involucradas en la biogénesis de fimbrias en H. pylori y caracterizar su expresión durante la formación de biopelícula. Métodos. Se emplearon herramientas bioinformáticas y moleculares, tales como la base de datos del NCBI para la búsqueda de secuencias de proteínas relacionadas con la biogénesis de fimbrias, así como la herramienta de PSI BLAST. Los alineamientos múltiples se realizaron con el programa T-COFFEE y HMMER. La predicción de las estructuras secundarias se realizó con ANTHEPROT y las estructuras terciarias se predijeron con el programa I-TASSER. Resultados. Se identificaron dos homólogos, jhp0257 y HP0272, de la proteína PilN de Campylobacter rectus y Xilella fastidiosa , la cual es parte de la maquinaria del ensamble de la fimbria tipo IV. Asimismo, las proteínas jhp0887 y HP0953 presentaron homología a nivel del péptido señal de PilA de P. aeruginosa , y la proteína HP0953 se sobreexpresó durante la formación de la biopelícula. Conclusiones. H. pylori posee proteínas homólogas a las proteínas de familias fimbriales, específicamente PilN y PilA, que ensamblan fimbria tipo IV en otras bacterias. Esta última tiene un nivel de expresión mayor durante la etapa inicial del proceso de formación de biopelícula.

Background. Colonization and chronic infection with Helicobacter pylori is the major contributing factor to the development of gastric cancer. A large repertoire of adhesins has been described that contribute to the adaptation of bacteria to a specific gastric niche. As in other pathogenic bacteria, H. pylori biofilm formation is central to survival on unfavorable environments. Type IV pili or fimbriae are responsible for the adhesion of many pathogenic bacteria (e.g., Escherichia coli, Pseudomonas aeruginosa and Vibrio cholerae ) to various surfaces. The aim of this study was to identify and analyze genes that might encode proteins involved in the biogenesis of fimbriae on H. pylori and characterize their expression during biofilm formation. Methods. PSI BLAST, bioinformatics and molecular tools were used as well as the NCBI database search for sequences related to protein biogenesis of fimbriae. Multiple alignments were performed using the HMMer and T-COFFEE programs. The secondary structure prediction was performed with ANTHEPROT and the tertiary structures were predicted with the I-Tasser. Results. We identified two counterparts-jhp0257 and HP0272-from protein of Campylobacter rectus and PilN Xilella fastidiosa , which is part of the machinery of assembly type IV fimbria. Similarly, proteins jhp0887 and HP0953 show homology from peptide PilA level of P. aeruginosa , and the HP0953 protein is overexpressed during the formation of the biofilm. Conclusions. H. pylori possesses proteins homologous to fimbrial protein families, specifically PilN and PilA, which join type IV fimbriae in other bacteria. The latter has a higher expression level during the initial stage of the formation of biofilm.

Expression of BART-5, BART-16 and BART-22, and NF-κB factor in classic Hodgkin's lymphoma in pediatric patients / Expresión de BART-5, BART -16 y BART -22, y del factor NF-κB en pacientes pediátricos con linfoma de Hodgkin clásico

Introducción. El linfoma de Hodgkin clásico es una neoplasia cuyo desarrollo se asocia con la presencia del virus del Epstein-Barr. No se conoce qué reguladores moleculares (como microRNAs del virus del Epstein-Barr) se expresan. Tampoco la asociación con factores proinflamatorios neoplásicos. El objetivo de este trabajo fue analizar la expresión de los microRNAs específicos del virus del Epstein-Barr, conocidos como BARTs (BART-5, BART-16 y BART-22), así como la expresión del factor NF-κB en pacientes pediátricos con linfoma de Hodgkin clásico. Métodos. Se seleccionaron 24 casos que cumplieron los criterios de inclusión. Entre las diferentes variedades, la esclerosis nodular y el de celularidad mixta fueron las más frecuentes. Resultados. Los resultados mostraron que la expresión del BART-5 fue la más frecuente (83%) en el linfoma de Hodgkin clásico. La expresión de BART-22 fue la segunda más frecuente, de 33.3% respecto a los testigos. En todos estos casos las diferencias fueron significativas respecto a los ganglios linfáticos reactivos (p <0.05). La expresión de NF-κB se encontró en 62.5% de los casos de linfoma de Hodgkin clásico, y se presentó en 83.3% de los ganglios linfáticos reactivos (p <0.05). La variedad de celularidad mixta lo expresó en 90% de los casos, lo que contrastó con 20% que presentó la variedad esclerosis nodular (p <0.05). Conclusiones. Se puede concluir que la expresión del BART-5 fue la más frecuente en los casos de linfoma de Hodgkin clásico. También, que el factor NF-κB es un indicador importante de inflamación, y presentó mayor expresión en los ganglios linfáticos activos.

Background. Classic Hodgkin's lymphoma (CHL) is a neoplasm in which the presence of, or infection by, the Epstein-Barr virus (EBV) is associated with disease development. Two aspects of this condition are currently unknown: first, whether molecular regulators such as the microRNAs of EBV are expressed and second, if there is an association with inflammation-promoting, neoplastic factors in pediatric CHL. The aim of the present study was to use RT-PCR to analyze the expression of the specific microRNAs of EBV called BARTs, specifically BARTs-5, -16 and -22 and that of factor NF-κB, also using RT-PCR. Methods. A total of 24 cases were selected after meeting the inclusion criteria, which involved different varieties of CHL including the nodular sclerosis (NS) and mixed cellularity (MC) types. These resulted in being the most common ones, each with a frequency of 41.6%. Results. BART-5 was the one most frequently expressed in CHL, at 83.3%. BART-22 was the second most frequent, at 33.3%, compared to 0% in controls (reactive lymph nodes, RLN). In all cases, the differences compared to RLN were significant (p <0.05). Expression of NF-κB was found in 62.5% of CHL cases and was present in 83.3% of RLN (p <0.05). The MC type expressed it in 90% of cases, compared to only 20% for the NS variety (p <0.05). Conclusions. BART-5 was the one most frequently expressed in CHL cases. NF-κB factor is an important indicator of inflammation most often expressed in RLN.

Detection of Epstein-Barr virus and genotyping based on EBNA2 protein in Mexican patients with hodgkin lymphoma: a comparative study in children and adults.

BACKGROUND: Epstein-Barr virus (EBV) is a member of the Herpesviridae family and is associated with Hodgkin lymphoma (HL). Isolates of EBV are classified according to sequence variation in the latency genes such as Epstein-Barr virus nuclear antigen (EBNA). EBNA2 contains the most divergent locus and is classified into type 1 and type 2 or EBNA2A and EBNA2B, respectively. We compared the frequency of EBV and the distribution of EBNA genotypes in Mexican children and adults with HL. PATIENTS AND METHODS: Lymph node biopsy specimens from children and adults with HL were embedded in paraffin. EBV was identified by LMP1 amplification and Epstein-Barr-encoded RNA EBER by in situ hybridization (ISH) and genotyped as EBNA2A or EBNA2B using nested polymerase chain reaction (PCR) and specific primers for the detection of subtype. RESULTS: Sixty-six samples were obtained from 3 hospitals-42 (63%) from children and 24 (37%) from adults with HL. Thirty-two of the 42 samples (76.1%) were positive for EBV in children and 16 of 24 (66.6%) samples were positive in adults (P = .41). In both children and adults, EBV was found more frequently in male patients. Thirty-four of 48 cases could be typed (70.8%). EBNA2A was found in 7/21 (33.3%) children and in 4/13 (30.8%) adults (P = 1.0), and EBNA2B was found in 10/21 (47.6%) children and in 9/13 (69.2%) adults (P = .22). A mix of subtypes was found in 4/21 (19%) children. CONCLUSION: EBV was found frequently in both children and adults with HL. EBNA2B was the most frequent subtype, and a high frequency of mixed subtypes was found in children.

Borreliosis, fiebre recurrente causada por espiroquetas. Informe de un caso / Borreliosis: recurrent fever due to spirochetes. Case report

Introducción. Las fiebres recurrentes son un grupo complejo de enfermedades causadas por diversas espiroquetas del género Borrelia, que el hombre adquiere por piquetes de piojos o garrapatas. El propósito de este trabajo es presentar un caso con esta enfermedad. Caso Clínico. Paciente femenino de 12 años de edad, que presentó inicialmente fiebre, cefalea, adenitis cervical y exantema toracoabdominal. La fiebre fue recurrente durante tres meses, con periodos 3 a 5 días e intervalos afebriles de 15 a 21 días. Los resultados de los exámenes de laboratorio fueron negativos para los anticuerpos anti Borrelia burgdorferi. En el frotis de sangre se identificaron espiroquetas. Fue tratada con diversos esquemas de antibióticos y, finalmente, con doxiciclina. Su evolución fue satisfactoria, y tres meses después aún se encuentra asintomática. Conclusiones. En el presente caso se consideró prudente, entre los diagnósticos diferenciales, incluir la posibilidad de fiebre recurrente atribuida a espiroquetemia. La dificultad para establecer el diagnóstico nos muestra la importancia de tener en mente este tipo de infecciones.

Background. Relapsing fever is a complex group of diseases caused by spirochetes of the genus Borrelia transmitted to humans by lice or ticks. The purpose of this study is to present a case of relapsing fever. Case report. A 12-year-old girl with no relevant clinical history was admitted with fever, headache, cervical adenitis, and thoracoabdominal exanthema. She had relapsing fever for 3 to 5 days with 15- to 21-day-intervals of apyrexia during the past 3 months. Laboratory exams were normal or negative including antibodies for Borrelia burdorferi. Peripheral blood smear showed spirochetes. She was treated with various antibiotics and finally doxycycline was added with a good response. The patient is asymptomatic and without sequelae 3 months after treatment. Conclusion. In the case we reported, relapsing fever due to spirochetemia was made during the differential diagnosis. Due to the difficulty in identification, it is important to have a clinical suspicion of this type of infection.

Flagella from five Cronobacter species induce pro-inflammatory cytokines in macrophage derivatives from human monocytes.

Cronobacter spp. are opportunistic pathogens linked to lie-threatening infections in neonates and contaminated powdered infant formula that has been epidemiologically associated with these cases. Clinical symptoms of Cronobacter include necrotizing enterocolitis, bacteremia, and meningitis. Flagella from C. sakazakii are involved in biofilm formation and its adhesion to epithelial cells. We investigated the role of flagella from C. sakazakii ST1 and ST4, C. malonaticus, C. muytjensii, C. turicensis and C. dublinensis during the activation of cytokines (IL-8, TNF-α, and IL-10) in macrophage derivatives from human monocytes, which has not been extensively studied. The production and identity of flagella from the five Cronobacter species were visualized and recognized with anti-flagella antibodies by immunogold labeling through transmission electron microscopy. Purified flagella were dissociated into monomers in 12% SDS-PAGE Coomassie blue-stained gels showing a band of ∼28 kDa and, in addition, mass spectrometry revealed the presence of several peptides that correspond to flagellin. Flagella (100 ng) induced the release of IL-8 (3314-6025 pg/ml), TNF-α (39-359 pg/ml), and IL-10 (2-96 pg/ml), in macrophage isolates from human monocytes and similar results were obtained when flagella were dissociated into monomers. Inhibition assays using three dilutions of anti-flagella antibodies (1∶10, 1∶100, and 1∶200) suppressed the secretion of IL-8, TNF-α, and IL-10 between 95-100% using 100 ng of protein. A transfection assay using 293-hTLR5 cells showed IL-8 release of 197 pg/ml and suppression in the secretion of IL-8 when anti-hTLR5-IgA antibodies were used at different concentrations. These observations suggest that flagella and flagellin are involved in an inflammatory response dependent on TLR5 recognition, which could contribute to the pathogenesis of the bacteria.

[Pediatric liver transplant program at Hospital Infantil de Mexico Federico Gomez]. / Programa de trasplante hepático pediátrico en el Hospital Infantil de México Federico Gómez.

This article reports the experience of the largest pediatric liver transplant (LT) program in México. Between June 1998 and May 2011, 76 LT were performed in 74 recipients, including 80% cadaveric-whole organ grafts and 20% segmental grafts, 12% of those coming from live donors and 8% from cadaver reduced donors. The most common indication for LT was biliary atresia (43%), followed by metabolic disorders (13%) and fulminant hepatitis (12%). Most of the recipients were infants or toddlers weighing <15 kg (age range 0.7-17.2 years, weight range 6.5-66 kg), 73% had moderate to severe malnutrition and 72% had multiples surgeries previous to LT. There were 9 cases of hepatic artery thrombosis (11.8%) and 2 portal vein thrombosis (2.6%), however, 8 of these 10 grafts were rescued with early thrombectomy and reanastomosis. All biliary complications (19 cases, 25%) were solved with medical or surgical interventions and did not cause any graft loss. Acute cellular rejection (30 cases, 39%) required thymoglobulin in only 3 cases and chronic rejection (4 cases, 5%) has been retransplanted in 2 cases. CMV infection or reactivation occurred in 30% of cases and easily responded to preemptive therapy. Nine recipients developed postLT neoplasias (7 post-transplant lymphoproliferative disorders, one multivisceral Kaposi sarcoma and one systemic smooth muscle tumor). Five of them responded to decreasing or discontinuing immunosuppression, and 2 are completely tolerant to the graft. The one and five-year patient survival for those LT performed during 2001-2011 was 85 and 75%. The first successful live donor LT in the country was performed in 2001 at this program, as was the first simultaneous liver-kidney transplant in a child. This is the largest and most successful pediatric LT series in the country. Our results demonstrate that pediatric LT is a feasible undertaking in Mexico, with survival rates similar to those of foreign centers.

Detection of fusion genes in formalin-fixed paraffin-embedded tissue sections of rhabdomyosarcoma by RT-PCR and fluorescence in situ hybridization in Mexican patients.

BACKGROUND AND AIMS: Rhabdomyosarcoma (RMS) is a pediatric tumor whose classification is based on histological criteria according to two main subgroups, embryonal RMS (ERMS) and alveolar RMS (ARMS). The majority but not all ARMS carry the specific PAX3(7)/FKHR translocation. The type of translocation in patients with ARMS defines the prognosis. METHODS: We retrospectively analyzed 30 cases of ARMS in Mexican patients and evaluated the fusion status of the genes using RT-PCR and fluorescence in situ hybridization (FISH) in formalin-fixed paraffin-embedded tissues (FFPET). RESULTS: From 25 samples (83%) with optimal RNA quality, RT-PCR revealed 15 cases (50%) with the t(2;13)/PAX3-FKHR. Only one case (3%) was positive to t(1;13)/PAX7-FKHR and nine cases (30%) were fusion-negative. Correspondingly, using FISH, the t(2;13)/PAX3-FKHR was found positive in 19 cases (63.5%), one case (3%) revealed the t(1;13)/PAX7/FKHR and ten cases (33.5%) were fusion-negative by this method. Five cases were not evaluable by RT-PCR but recovered by FISH. Only four of the total revealed t(2;13); the other was fusion-negative. CONCLUSIONS: FISH technique is more sensitive when FFPET is used to describe the chromosomal translocation of ARMS. These Latino patients showed an association of the t(2;13) in older patients (mean: 9 years) and negative translocation in younger patients (mean: 4 years) (p <0.05). Both t(2;13) and negative-fusion were present in patients with clinical stages III and IV (p <0.05). There was a nonsignificant trend of t(2;13) to lower overall survival than negative-fusion status.