Síndrome de Alagille, reporte de un caso y revisión de la literatura / Alagille Syndrome, case study and literature review / Sindrome de Alagille, relato de caso e revisão de literatura

El síndrome de Alagille es una patología poco frecuente, de herencia autosómica dominante. Se caracteriza por la presencia de colestasis crónica progresiva ocasionada por hipoplasia de las vías biliares; anomalías vertebrales, oculares y cardíacas, y fenotipo facial particular. Entre sus diagnósticos diferenciales se incluyen las infecciones, enfermedades endocrinometabólicas, atresia biliar y causas idiopáticas. El pronóstico de este síndrome es variable y depende de la entidad de la afectación hepática y los defectos cardiovasculares. El abordaje terapéutico suele ser interdisciplinario e individualizado, enfocado en el control sintomático, prevención de la malnutrición y el déficit de vitaminas liposolubles. Se presenta el caso de un lactante de 2 meses en el que se estudiaron las causas más frecuentes de colestasis y se llegó al diagnóstico de síndrome de Alagille. Se describe su abordaje terapéutico y seguimiento.

Alagille syndrome is an inherited autosomal dominant rare disease. It is characterized by the presence of progressive chronic cholestasis caused by hypoplasia of the bile ducts; vertebral, ocular and cardiac anomalies, and particular facial phenotype. Its differential diagnoses include infections, endocrine-metabolic diseases, biliary atresia and idiopathic causes. The prognosis of this syndrome is variable and depends on the degree of liver involvement and cardiovascular defects. The therapeutic approach is usually interdisciplinary and customized, focused on symptomatic control, prevention of malnutrition and fat-soluble vitamin deficiency. We present the case of a 2-month-old infant in whom the most frequent causes of cholestasis were studied and to whom Alagille Syndrome was diagnosed. We hereby describe its therapeutic approach and follow-up.

A síndrome de Alagille é uma doença rara, hereditária, autossômica e dominante. Caracteriza-se pela presença de colestase crônica progressiva causada por hipoplasia das vias biliares; anomalias vertebrais, oculares e cardíacas e fenótipo facial particular. Seus diagnósticos diferenciais incluem infecções, doenças endócrino-metabólicas, atresia biliar e causas idiopáticas. O prognóstico desta síndrome é variável e depende do grau de envolvimento hepático e defeitos cardiovasculares. A abordagem terapêutica geralmente é interdisciplinar e personalizada, focada no controle sintomático, prevenção da desnutrição e deficiência de vitaminas lipossolúveis. Apresentamos o caso de uma criança de 2 meses de idade em que foram estudadas as causas mais frequentes de colestase e a quem foi diagnosticada Síndrome de Alagille. Descrevemos a sua abordagem terapêutica e seguimento.

PALB2 germline mutations in a multi-gene panel testing cohort of 1905 breast-ovarian cancer patients in Argentina.

PURPOSE: PALB2 variants have been scarcely described in Argentinian and Latin-American reports. In this study, we describe molecular and clinical characteristics of PALB2 mutations found in multi-gene panels (MP) from breast-ovarian cancer (BOC) families in different institutions from Argentina. METHODS: We retrospectively identified PALB2 pathogenic (PV) and likely pathogenic (LPV) variants from a cohort of 1905 MP results, provided by one local lab (Heritas) and SITHER (Hereditary Tumor Information System) public database. All patients met hereditary BOC clinical criteria for testing, according to current guidelines. RESULTS: The frequency of PALB2 mutations is 2.78% (53/1905). Forty-eight (90.5%) are PV and five (9.5%) are LPV. Most of the 18 different mutations (89%) are nonsense and frameshift types and 2 variants are novel. One high-rate recurrent PV (Y551*) is present in 43% (23/53) of the unrelated index cases. From the 53 affected carriers, 94% have BC diagnosis with 14% of bilateral cases. BC phenotype is mainly invasive ductal (78%) with 62% of hormone-receptor positive and 22% of triple negative tumors. Self-reported ethnic background of the cohort is West European (66%) and native Latin-American (20%) which is representative of Buenos Aires and other big urban areas of the country. CONCLUSION: This is the first report describing molecular and clinical characteristics of PALB2 carriers in Argentina. Frequency of PALB2 PV in Argentinian HBOC families is higher than in other reported populations. Y551* is a recurrent mutation that seems to be responsible for almost 50% of PALB2 cases.

Genomic insights into an andean multiresistant soil actinobacterium of biotechnological interest.

Central-Andean Ecosystems (between 2000 and 6000 m above sea level (masl) are typical arid-to-semiarid environments suffering from the highest total solar and ultraviolet-B radiation on the planet but displaying numerous salt flats and shallow lakes. Andean microbial ecosystems isolated from these environments are of exceptional biodiversity enduring multiple severe conditions. Furthermore, the polyextremophilic nature of the microbes in such ecosystems indicates the potential for biotechnological applications. Within this context, the study undertaken used genome mining, physiological and microscopical characterization to reveal the multiresistant profile of Nesterenkonia sp. Act20, an actinobacterium isolated from the soil surrounding Lake Socompa, Salta, Argentina (3570 masl). Ultravioet-B, desiccation, and copper assays revealed the strain's exceptional resistance to all these conditions. Act20's genome presented coding sequences involving resistance to antibiotics, low temperatures, ultraviolet radiation, arsenic, nutrient-limiting conditions, osmotic stress, low atmospheric-oxygen pressure, heavy-metal stress, and toxic fluoride and chlorite. Act20 can also synthesize proteins and natural products such as an insecticide, bacterial cellulose, ectoine, bacterial hemoglobin, and even antibiotics like colicin V and aurachin C. We also found numerous enzymes for animal- and vegetal-biomass degradation and applications in other industrial processes. The resilience of Act20 and its biotechnologic potential were thoroughly demonstrated in this work.

La región sudeste del Gran Buenos Aires frente a la pandemia Evaluación de la ampliación del sistema de salud en el marco de la COVID 19 / The Southeastern region of the Buenos Aires Province metropolitan area in the face of the pandemic: evaluation of the expansion of the health system in the framework of COVID-19

INTRODUCCIÓN: La región sudeste del Gran Buenos Aires (GBA) reformuló el sistema público de salud por la pandemia de COVID19. Entre las medidas que se tomaron, está la ampliación del número de camas mediante la construcción y puesta en marcha de tres hospitales. OBJETIVO: Evaluar el impacto de la ampliación del número de camas en los resultados de internación de los pacientes asistidos por los efectores públicos de salud durante el período de estudio (8 de abril de 2020 al 11 de septiembre de 2020). MÉTODOS: Estudio descriptivo a partir de información registrada en el Tablero COVID-19, software de gestión desarrollado por el equipo del Instituto del Cálculo de la Universidad de Buenos Aires, en el que se obtienen datos de cada paciente internado en la red de efectores de salud; se evalúan los resultados del efecto del aumento de la capacidad instalada. RESULTADOS: Se registraron 2 306 pacientes internados, de los cuales 266 (11,54%) requirieron internación en unidad de cuidados intensivos (UCO), 1 786 (77,4%) en cuidados intermedios y 254 (11%) pacientes en sala general. La media de edad fue de 50,63 y los pacientes de sexo masculino representaron el 55,5% del total. Se produjeron 253 muertes (10,97%), de las cuales el 64% fueron hombres. El 58,3% del total tenían enfermedades preexistentes, estos tienen un riesgo 90% más alto que quienes no las tenían. El promedio total de ocupación de camas en UCI fue del 40,7%, mientras que el de ocupación en cuidados intermedios fue de 61,5%. Sin los hospitales nuevos, 169 pacientes (9,46%) no hubieran tenido camas en cuidados intermedios y 31 pacientes (11,6%) no hubieran tenido cama en la UCI. DISCUSIÓN: El sistema de salud de la región sudeste del GBA se preparó de manera adecuada gracias a la ampliación del número de camas de internación.

Distribution of maternal lineages in hunter-gatherer societies of the southern coast of Tierra del Fuego, Argentina.

OBJECTIVES: The aim of this work is to explore the maternal genetic diversity of hunter-gatherers of the southern Tierra del Fuego, specifically the north coast of Beagle Channel, the Península Mitre, and Isla de los Estados through ancient mitochondrial DNA analysis. MATERIALS AND METHODS: The hypervariable regions 1 and 2 of the mitochondrial genome of five individuals from the north coast of Beagle Channel, six individuals from Península Mitre, and one individual from Isla de los Estados were analyzed. Through diversity statistics, Analysis of Molecular Variance (AMOVA), and Median Joining networks analyses, maternal relationships in the region were evaluated and phylogenetic similarities between ancient and contemporary populations of Tierra del Fuego were determined. RESULTS: The mitochondrial DNA lineages from the ancient individuals analyzed reveals the presence of subclades C1b and D1g. Pattern of decreasing genetic diversity toward the South is observed. The AMOVAs performed found no statistically significant differences between individuals of the north coast of Beagle Channel and Península Mitre-Isla de los Estados, and modern Yámana populations. Median joining network of haplotypes of clades C1 and D1g, show the same results. DISCUSSION: Ethnohistoric and ethnographic records of Península Mitre show that this region was occupied during the 19th century by Haush or Manekenk populations, although their biological, cultural, and subsistence characterization is unclear. We explore their maternal lineages and encounter low levels of genetic diversity and the absence of population differentiation with modern Yámana groups. We suggest that Península Mitre-Isla de los Estado was part of the same hunting and gathering populations as those of the Beagle Channel.

Bacterial Infection Disrupts Clock Gene Expression to Attenuate Immune Responses.

The circadian clock modulates immune responses in plants and animals; however, it is unclear how host-pathogen interactions affect the clock. Here we analyzed clock function in Arabidopsis thaliana mutants with defective immune responses and found that enhanced disease susceptibility 4 (eds4) displays alterations in several circadian rhythms. Mapping by sequencing revealed that EDS4 encodes the ortholog of NUCLEOPORIN 205, a core component of the inner ring of the nuclear pore complex (NPC). Consistent with the idea that the NPC specifically modulates clock function, we found a strong enrichment in core clock genes, as well as an increased nuclear to total mRNA accumulation, among genes that were differentially expressed in eds4 mutants. Interestingly, infection with Pseudomonas syringae in wild-type (WT) plants downregulated the expression of several morning core clock genes as early as 1 h post-infection, including all members of the NIGHT LIGHT-INDUCIBLE AND CLOCK-REGULATED (LNK) gene family, and this effect was attenuated in eds4. Furthermore, lnk mutants were more susceptible than the WT to P. syringae infection. These results indicate that bacterial infection, acting in part through the NPC, alters core clock gene expression and/or mRNA accumulation in a way that favors bacterial growth and disease susceptibility.

A novel heterozygous STAT5B variant in a patient with short stature and partial growth hormone insensitivity (GHI).

BACKGROUND: The most frequent monogenic causes of growth hormone insensitivity (GHI) include defects in genes encoding the GH receptor itself (GHR), the signal transducer and activator of transcription (STAT5B), the insulin like-growth factor type I (IGF1) and the acid-labile subunit (IGFALS). GHI is characterized by a continuum of mild to severe post-natal growth failure. OBJECTIVE: To characterize the molecular defect in a patient with short stature and partial GHI. PATIENT AND METHODS: The boy was born at term adequate for gestational age from non-consanguineous normal-stature parents. At 2.2 years, he presented proportionate short stature (height -2.77 SDS), wide forehead and normal mental development. Whole-exome analysis and functional characterization (site-directed mutagenesis, dual luciferase reporter assay, immunofluorescence and western immunoblot) were performed. RESULTS: Biochemical and endocrinological evaluation revealed partial GH insensitivity with normal stimulated GH peak (7.8 ng/mL), undetectable IGF1 and low IGFBP3 levels. Two heterozygous variants in the GH-signaling pathway were found: a novel heterozygous STAT5B variant (c.1896G>T, p.K632N) and a hypomorphic IGFALS variant (c.1642C>T, p.R548W). Functional in vitro characterization demonstrated that p.K632N-STAT5b is an inactivating variant that impairs STAT5b activity through abolished phosphorylation. Remarkably, the patient's immunological evaluation displayed only a mild hypogammaglobulinemia, while a major characteristic of STAT5b deficient patients is severe immunodeficiency. CONCLUSIONS: We reported a novel pathogenic inactivating STAT5b variant, which may be associated with partial GH insensitivity and can present without severe immunological complications in heterozygous state. Our results contribute to expand the spectrum of phenotypes associated to GHI.

Chitosan-Hydroxyapatite Scaffold for Tissue Engineering in Experimental Lumbar Laminectomy and Posterolateral Spinal Fusion in Wistar Rats.

STUDY DESIGN: Experimental study with an animal model. PURPOSE: To evaluate the role of a chitosan and hydroxyapatite composite for spinal fusion in a lumbar experimental model based on regenerative tissue engineering principles. OVERVIEW OF LITERATURE: Chitosan and hydroxyapatite represent an alternative biodegradable implant material for tissue engineering and regeneration. The combination of chitosan and hydroxyapatite in a 20:80 ratio could potentiate their individual properties as an implantable composite for experimental laminectomy. METHODS: Phase I: design and synthesis of a porous composite scaffold composed of chitosan-hydroxyapatite using a freeze drying technique. Phase II: experimental microsurgical lumbar laminectomy at L5. A total of 35 Wistar rats were categorized into three experimental groups: control (laminectomy alone), experimental (laminectomy with implant), and reference (intact spine) (n=5 per group). Postoperative structural and functional evaluations were performed using computed tomography scans. In addition, radiologic, clinical, histological, and immunohistochemical microstructures were evaluated. RESULTS: At the laminectomy site, the composite implant induced bone regeneration, which was observed in the axial reconstruction of the rat lumbar spine in all cases. Biomechanical changes in the lumbar spine were observed by radiology in both groups after the surgery. The posterolateral space was covered by a bone structure in the treated spine, a condition not seen in the control group. The range of motion was 7.662°±0.81° in the scaffold group versus 20.72°±3.47° in the control group. Histological findings revealed qualitatively more bone tissue formation in the implant group. CONCLUSIONS: A composite of chitosan-hydroxyapatite at a 20:80 ratio induced bone formation after experimental laminectomy in rats and led to spinal fusion, which was assessed by radiology and biomechanical tests. No functional complications in posture or walking were observed at 90 days post-surgery, despite biomechanical changes in the spine.

Improvement of alfalfa forage quality and management through the down-regulation of MsFTa1.

Alfalfa (Medicago sativa L.) is one of the most important forage crops worldwide. As a perennial, alfalfa is cut several times each year. Farmers face a dilemma: if cut earlier, forage nutritive value is much higher but regrowth is affected and the longevity of the stand is severely compromised. On the other hand, if alfalfa is cut later at full flower, stands persist longer and more biomass may be harvested, but the nutritive value diminishes. Alfalfa is a strict long-day plant. We reasoned that by manipulating the response to photoperiod, we could delay flowering to improve forage quality and widen each harvesting window, facilitating management. With this aim, we functionally characterized the FLOWERING LOCUS T family of genes, represented by five members: MsFTa1, MsFTa2, MsFTb1, MsFTb2 and MsFTc. The expression of MsFTa1 correlated with photoperiodic flowering and its down-regulation led to severe delayed flowering. Altogether, with late flowering, low expression of MsFTa1 led to changes in plant architecture resulting in increased leaf to stem biomass ratios and forage digestibility. By manipulating photoperiodic flowering, we were able to improve the quality of alfalfa forage and management, which may allow farmers to cut alfalfa of high nutritive value without compromising stand persistence.

Experiencia en la utilización de cánula nasal de alto flujo en niños con infecciones respiratorias agudas hospitalizados en un sector de internación / Use of high flow nasal cannula in hospitalized children with acute respiratory infections / Uso de cânula nasal de alto fluxo em crianças hospitalizadas com infecções respiratórias agudas

Resumen: Introducción: las infecciones respiratorias agudas bajas (IRAB) constituyen la principal causa de ingreso hospitalario en menores de 2 años. La utilización de cánula nasal de alto flujo (CNAF) es un instrumento terapéutico eficaz para evitar la ventilación invasiva, especialmente para los pacientes menores de 6 meses que constituyen el grupo de mayor riesgo. Objetivos: presentar la experiencia en la implementación de la terapia con CNAF en pacientes menores de 2 años con IRAB con insuficiencia respiratoria tratados en un sector de internación de infecciones respiratorias virales y analizar la población derivada a sectores de mayor complejidad. Pacientes y método: estudio observacional prospectivo en el que se incluyeron pacientes menores de 2 años con IRAB e insuficiencia respiratoria que recibieron tratamiento con CNAF, desde el 1° de junio al 31 de agosto del 2015 en un sector de internación del Hospital Pediátrico del Centro Hospitalario Pereira Rossell (HP/CHPR) de Montevideo, Uruguay. Resultados: se incluyeron 125 pacientes, 47 niñas y 78 varones, con una mediana de edad de 3 meses (16 días - 24 meses). En el 53% de ellos se identificó VRS. La duración de la terapia con CNAF tuvo una mediana de 69 horas (4 - 192 horas). La mediana del score de TAL modificado previo a su utilización fue de 7 (rango 5 - 9) y a las dos horas de 5 (rango 3 - 8). La terapia con CNAF se acompañó de una reducción significativa de la frecuencia cardíaca (FC). No se observaron efectos adversos ni complicaciones por la técnica. Requirieron ingreso a sectores de mayor complejidad (unidad de cuidados intensivos UCI o cuidados respiratorios especiales agudos CREA) el 38% (n=47), de los cuales el 36% (n=17) requirió asistencia ventilatoria mecánica invasiva (AVMI), el 25% (n=12) ventilación no invasiva (VNI) y el 38% (n=18) continuó recibiendo tratamiento con CNAF. Los menores de 3 meses requirieron derivación a sectores de mayor complejidad con más frecuencia (p=0,0036). Conclusiones: la utilización de CNAF pudo ser implementada sin complicaciones en una sala de internación pediátrica. El 62% de los pacientes no requirió otro tipo de apoyo respiratorio. Los menores de 3 meses requirieron traslado a cuidados críticos con mayor frecuencia.

Summary: Introduction: acute lower respiratory infections (LRTI) are the leading cause of hospitalization in children under 2 years of age. High-Flow Oxygen (HFO) is a highly effective method to prevent invasive ventilation, even for patients under 6 months of age, the highest-risk group. Objective: to present our experience and results for patients under 2 years of age with LRTI and moderate or severe respiratory distress treated with HFO and to analyze the subgroup of patients that needed to be transferred to other hospital units to continue their treatment. Patients and method: patients under 2 years of age with LRTI and respiratory failure who required HFO were included in a prospective observational study carried out between June 1 and August 31, 2015 at the Inpatient Area of the Pediatric Hospital, Centro Hospitalario Pereira Rossell (PH/CHPR), Montevideo, Uruguay. Results: 125 patients were included. 47 girls and 78 boys with a median age of 3 months (16 days-24 months). 53% of them were RSVs positive. The median connection time was 69 hours (Range 4 -192). The median for the modified TAL score was 7 (Range 5-9) and 5 (Range 3-8) before connection and 2 hours later respectively. HFO resulted into a significant reduction of heart rate. No adverse effects or complications were observed. 38% (n = 47) of patients were transferred to intensive care or special acute respiratory care but just a 36% (n = 17) of them needed mechanical ventilation and 25.5% (n = 12) needed non-invasive ventilation (NIV); the remaining 18 patients continued receiving HFO. Patients under 3 months of age needed to be transferred to ICU more often than older ones (p = 0.0036) Conclusions: the HFO technique could be implemented without complications in pediatric units. 62% of patients did not need additional respiratory support. Patients under 3 months of age needed to be transferred to Intensive Care more often than older patients.

Resumo: Introdução: as infecções respiratórias agudas inferiores (IRA) são a principal causa de hospitalização em crianças menores de 2 anos. O oxigênio de alto fluxo (OAF) é um método altamente eficaz para prevenir a ventilação invasiva, mesmo em pacientes com menos de 6 meses de idade, o grupo de maior risco. Objetivo: apresentar nossa experiência e resultados nos pacientes com menos de 2 anos de idade com IRA com dificuldade respiratória moderada ou grave tratados com OAF e analisar o subgrupo de pacientes que precisaram ser transferidos para outras áreas hospitalares para continuar o seu tratamento. Pacientes e método: pacientes com menos de 2 anos de idade com ITRI e insuficiência respiratória que necessitaram de OAF foram incluídos em um estudo observacional prospectivo realizado entre 1 de junho e 31 de agosto de 2015 na Área de Internação do Hospital Pediátrico, Centro Hospitalario Pereira Rossell (PH / CHPR), Montevidéu, Uruguai. Resultados: 125 pacientes foram incluídos. 47 meninas e 78 meninos com idade média de 3 meses (16 dias a 24 meses). 53% deles foram positivos para o VSR. O tempo médio de conexão foi de 69 horas (Faixa 4 -192). A mediana do escore TAL modificado foi de 7 (intervalo 5-9) e 5 (intervalo 3-8) antes da conexão e 2 horas depois, respectivamente. HFO resultou em uma redução significativa na frequência cardíaca. Não foram observados efeitos adversos ou complicações. 38% (n = 47) dos pacientes foram transferidos para tratamento intensivo ou respiratório agudo especial, mas apenas 36% (n = 17) deles necessitaram de ventilação mecânica e 25,5% (n = 12) necessitaram de ventilação não invasiva (VNI); os 18 pacientes restantes continuaram recebendo HFO. Pacientes com menos de 3 meses de idade precisaram ser transferidos para UTI mais frequentemente do que os outros (p = 0,0036) Conclusões: a técnica OAF poderia ser implementada sem complicações em unidades pediátricas. 62% dos pacientes não precisaram de suporte respiratório adicional. Pacientes com menos de 3 meses de idade precisaram ser transferidos para terapia intensiva com mais frequência do que pacientes mais velhos.

Utilización de probióticos, antisecretores y zinc en la gastroenteritis aguda en pediatría en Uruguay / Use of probiotic, antisecretory drugs and zinc for acute gastroenteritis in Uruguayan pediatric patients / Uso de probióticos, drogas anti-secretoras e zinco em gastroenterite aguda em pediatria no Uruguai

Resumen: Introducción: luego de la difusión de las sales de rehidratación oral, que resultó en una radical disminución en la morbimortalidad por gastroenteritis aguda (GEA), existe interés creciente en tratamientos destinados a reducir su duración. Objetivo: conocer la utilización de los tratamientos para disminuir la duración de la GEA (probióticos, antisecretores, zinc) por los pediatras uruguayos. Método: encuesta online difundida a través de la Sociedad Uruguaya de Pediatría. Resultados: n=245 encuestas de pediatras procedentes de 17/19 departamentos del país (59% Montevideo). El 39,4% no indica probióticos en tratamiento de GEA; 5,8% lo indica siempre, y 49% en algunas situaciones (15,2% ingreso hospitalario; 21,2% inmunodeprimidos). La elección se basa en 13% en evidencia científica y 47,9% por disponibilidad en el lugar de cobertura. El 32,2% conoce adecuadamente el impacto en la duración de la diarrea. El 61,4% nunca utiliza antisecretores y 24,9% lo utiliza (96,6% racecadotrilo; 3,4% loperamida) en algunas situaciones (56,7% <5 años; 41,6% >5 años; 21,6% en pacientes que requieren internación). El 22% conoce adecuadamente el impacto de su utilización en la duración de la diarrea. En relación con el uso de zinc, 76,3% lo utiliza en algunas situaciones (64% pacientes desnutridos; 46% pacientes internados; 31% >6 meses y 26% <6 meses), y 6,9% lo utiliza siempre). Conclusiones: existe una amplia utilización de probióticos y zinc y un escaso uso de antisecretores en nuestro medio. Los pediatras uruguayos reconocen el posible rol de estos fármacos en la GEA. Un alto porcentaje de los pediatras no conoce la evidencia que fundamenta su uso. Es necesaria la implementación de programas de educación médica continua para guiar su uso.

Summary: Introduction: there is an increasing interest regarding treatments that shorten the duration of acute gastroenteritis (AG) in children, although little is known about it in Uruguay. Aim: that Uruguayan pediatricians get acquainted with probiotics, antisecretory drugs and zinc treatments. Methods: online survey sent to pediatricians members of the Uruguayan Pediatrics Association. Results: n=245 surveys carried out by pediatricians at 17/19 departments in Uruguay (59% from Montevideo). 39.4% stated they had not used probiotics to treat AG, 5.8% had always used it and 49% used it depending on the situation (15.2% used it with inpatients and 21.2% with immune depressed children). The choice of probiotics was based: 13% on scientific evidence and 47.9% on availability. 32.2% of pediatricians knew the real impact of probiotics on the duration of AG. 61.4% did not use antisecretory drugs and 24.9% used them depending on the situation (56.7% <5 years old, 41.6% >5 years, 21.6% inpatients). 96.6% of them chose Racecadotril and 3.4% Loperamide. 22% were aware of the real impact of the duration of AG. 76.3% of pediatricians used zinc to treat GEA in some situations (64% malnourished children, 46% inpatients, 31% >6 months, 26% <6 months) and 6.9% always used it. Conclusion: while probiotics and zinc are widely used, antisecretory drugs are slightly used as AG treatments in Uruguay. Uruguayan pediatricians identify the potential useful role of these treatments for AG, although many of them are not aware of its real use, so it is necessary to offer permanent medical training programs in this respect.

Resumo: Introdução: há um interesse crescente em tratamentos para reduzir a duração da gastroenterite aguda (GA) em pediatria, embora ainda há pouco conhecimento do tratamento no Uruguai. Objetivo: que os pediatras uruguaios se familiarizem com os tratamentos com probióticos, medicamentos anti-secretores e zinco. Métodos: pesquisa online enviada aos pediatras da Sociedade Uruguaia de Pediatria. Resultados: n = 245 pesquisas realizadas por pediatras em 17/19 departamentos do Uruguai (59% de Montevidéu). 39,4% afirmaram não ter usado probióticos para tratar a GEA, 5,8% sempre usaram e 49% usaram dependendo da situação (15,2% usaram com pacientes internados e 21,2% com imunossuprimidos). A escolha dos probióticos foi baseada: 13% na evidência científica e 47,9% na disponibilidade. 32,2% dos pediatras conheciam o real impacto dos probióticos na duração da GA. 61,4% não faziam uso de drogas antisecretoras e 24,9% usaram dependendo da situação (56,7% <5 anos, 41,6% ± 5 anos, 21,6% internados). 96,6% deles escolheram Racecadotril e 3,4% Loperamida. 2% conheciam o impacto real na duração da GA. 76,3% dos pediatras usaram zinco para tratar a GA em algumas situações (64% das crianças desnutridas, 46% dos pacientes internados, 31% >6 meses, 26% <6 meses) e 6,9% sempre usaram. Conclusão: os probióticos e o zinco são amplamente utilizados, enquanto os antisecretores são pouco usados no Uruguai. Pediatras uruguaios tem identificado o potencial papel útil desses tratamentos para a GA, embora muitos deles ainda não conheçam seu uso real, por isso é necessário oferecer programas permanentes de capacitação médica nesse assunto.

A different gut microbiome linked to inflammation found in cirrhotic patients with and without hepatocellular carcinoma.

INTRODUCTION AND AIM: A pro-oncogenic intestinal microbiome was observed in murine models; however, no specific microbiome in patients with hepatocellular carcinoma (HCC) has been reported. We aimed to compare the gut microbiome found in cirrhotic patients with or without HCC. MATERIALS AND METHODS: From 407 patients with Child Pugh A/B cirrhosis prospectively followed, 25 with HCC (cases) were matched with 25 without HCC (wo-HCC) in a 1:1 ratio according to age, gender, etiology, Child Pugh and severity of portal hypertension. In addition, results were also compared with 25 healthy subjects. Fecal stool samples were sequenced for the V3-V4 region of the microbial 16S rRNA (Illumina MiSeq Platform). Plasma cytokines were quantified including interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). RESULTS: We found a differential abundance in family members of Firmicutes with a 3-fold increase of Erysipelotrichaceae and a 5-fold decrease in family Leuconostocaceae in HCC when compared to wo-HCC controls. Genus Fusobacterium was found to be 5-fold decreased in HCC vs wo-HCC. The ratio bacteriodes/prevotella was increased in HCC. Three operational taxonomic units (OTUs), genus Odoribacter and Butyricimonas were more abundant in HCC, whereas a decreased abundance in Lachnospiraceae family genus Dorea was observed in HCC patients. A Random Forest model trained with differential abundant taxa correctly classified HCC individuals. This pattern was associated with an inflammatory milieu with a putative increased activation of NOD-like receptor pathways. CONCLUSION: We found a pattern of microbiome linked to inflammation that could be potentially useful as HCC biomarker after follow-up validation studies.

Shade delays flowering in Medicago sativa.

Shade-intolerant plants respond to the decrease in the red (R) to far-red (FR) light ratio (R:FR) occurring under shade by elongating stems and petioles and by re-positioning leaves, in a race to outcompete neighbors for the sunlight resource. In some annual species, the shade avoidance syndrome (SAS) is accompanied by the early induction of flowering. Anticipated flowering is viewed as a strategy to set seeds before the resources become severely limiting. Little is known about the molecular mechanisms of SAS in perennial forage crops like alfalfa (Medicago sativa). To study SAS in alfalfa, we exposed alfalfa plants to simulated shade by supplementing with FR light. Low R:FR light produced a classical SAS, with increased internode and petiole lengths, but unexpectedly also with delayed flowering. To understand the molecular mechanisms involved in uncoupling SAS from early flowering, we used a transcriptomic approach. The SAS is likely to be mediated by increased expression of msPIF3 and msHB2 in low R:FR light. Constitutive expression of these genes in Arabidopsis led to SAS, including early flowering, strongly suggesting that their roles are conserved. Delayed flowering was likely to be mediated by the downregulation of msSPL3, which promotes flowering in both Arabidopsis and alfalfa. Shade-delayed flowering in alfalfa may be important to extend the vegetative phase under suboptimal light conditions, and thus assure the accumulation of reserves necessary to resume growth after the next season.

Photolyases and Cryptochromes in UV-resistant Bacteria from High-altitude Andean Lakes.

"High-altitude Andean Lakes" (HAAL) are pristine environments harboring poly-extremophilic microbes that show combined adaptations to physical and chemical stress such as large daily ambient thermal amplitude, extreme solar radiation levels, intense dryness, alkalinity, high concentrations of arsenic (up to 200 ppm) and dissolved salts. In this work, we compared the UV resistance profiles, pigment content and photoreactivation abilities of three UV-resistant bacteria isolated from distinct niches from HAALs, that is Acinetobacter sp. Ver3 (water, Lake Verde; 4400 m), Exiguobacterium sp. S17 (stromatolite, Lake Socompa, 3570 m) and Nesterenkonia sp. Act20 (soil, Lake Socompa, 3570 m). UV resistance ability of HAAL's strains indicate a clear adaptation to high radiation exposure encountered in their original habitat, which can be explained by genetic and physiological mechanisms named as the UV-resistome. Thus, the UV-resistome depends on the expression of a diverse set of genes devoted to evading or repairing the damage it provoked direct or indirectly. As pigment extraction and photoreactive assays indicate the presence of photoactive molecules, we characterized more in detail proteins with homology to photolyases/cryptochromes members (CPF). Phylogenetic analyses, sequence comparison and 3D modeling with bona fide CPF members were used to prove the presence of functional domains and key residues in the novel proteins.

Exome-first approach identified novel INDELs and gene deletions in Mowat-Wilson Syndrome patients.

Mowat-Wilson syndrome (MWS) is characterized by severe intellectual disability, absent or impaired speech and microcephaly, with a gradual post-natal onset. The syndrome is often confused with other Angelman-like syndromes (ALS) during infancy, but in older children and adults, the characteristic facial gestalt of Mowat-Wilson syndrome allows it to be distinguished easily from ALS. We report two cases in which an exome-first approach of patients with MWS identified two novel deletions in the ZEB2 gene ranging from a 4 base deletion (case 1) to at least a 573 Kb deletion (case 2).

Multiple vertebral fractures at the "dr. manuel dufoo" spine clinic / Fraturas vertebrais múltiplas na clínica de coluna "dr. manuel dufoo" / Fracturas vertebrales múltiples en la clínica de columna "dr. manuel dufoo"

ABSTRACT Objective: To establish the frequency of presentation of multiple vertebral fractures and evaluate the relationship between the postsurgical condition and the initial neurological lesion, as well as to report the associated injuries in this group of patients. Methods: We conducted a review of patients with spinal trauma and a diagnosis of multiple vertebral fractures who were admitted to the "Dr. Manuel Dufoo Olvera" Spine Clinic of the Secretary of Health of Mexico City from January 1,2014 to June 30, 2017. The multiple fractures were classified as either contiguous or non-contiguous, according to the number of vertebral bodies and levels affected. The statistical analysis was conducted using formulas of descriptive statistics and the information was then tabulated and graphed to assess the relationship between the anatomical classification and the degree of neurological injury. Results: We observed 530 patients, of whom 47 met the criteria. Thirty-one (65.95%) of the cases corresponded to contiguous fractures and 16 cases (34.05%) to non-contiguous fractures. Fourteen patients (29.78%) with neurological integrity were classified as ASIA D, 20 patients (42.58%) with complete lesion as ASIA A, 7 seven patients (14.89%) as ASIA B, and 6 patients (12.76%) with partial injury as ASIA C. Conclusions: The correlation between the classification of vertebral injuries and the presence of neurological lesion did not show significant differences between contiguous and non-contiguous fractures. Level of Evidence II; Retrospective.

RESUMO Objetivos: Estabelecer a frequência de apresentação de múltiplas fraturas vertebrais e avaliar a relação de sua condição pós-cirúrgica e a lesão neurológica inicial, bem como relatar as lesões associadas neste grupo de pacientes. Métodos: Uma revisão dos casos com traumatismo espinhal e diagnóstico de fratura vertebral múltipla, que entraram no Spine Clinic " Dr Manuel Dufoo Olvera " Secretário da Cidade do México saúde da coluna vertebral, durante o período de 1 de janeiro de 2014 a 30 de Junho de 2017. A classificação divide fraturas múltiplas como contíguas e não contíguas, seguido pelo número de pessoas afetadas e os corpos de nível. A análise estatística foi realizada utilizando fórmulas statística descritivas, então tabuladas e as informações representadas graficamente. Para avaliar a relação entre a classificação anatômica e do grau de lesão neurológica. Resultados: 530 Pacientes foram observados, dos quais 47 apresentaram os critérios necessários. 31 pacientes (65,95%) do estudo foram classificados com fraturas adjacentes contíguas e 16 casos (34,05%) como não contíguas. 14 doentes (29,78%) foram classificados com integridade neurológica ÁSIA D, 20 doentes (42,58%) apresentaram lesão completa ÁSIA A, sete doentes (14,89%) na ASIA B e seis doentes. (12,76%) com lesão incompleta ÁSIA C. Conclusão: A correlação entre a classificação das lesões da coluna vertebral e a presença de lesão neurológica não mostraram diferenças significativas entre fraturas adjacentes e não adjacentes. Nível de Evidência II; Restrospectivo.

RESUMEN Objetivo: Establecer la frecuencia de presentación de las fracturas vertebrales múltiples y evaluar la relación de su condición postquirúrgica y la lesión neurológica inicial, así como relatar las lesiones asociadas en este grupo de pacientes. Métodos: Se realiza una revisión de los casos con traumatismo raquimedular y diagnóstico de fractura vertebral múltiple que ingresaron a la Clínica de Columna "Dr. Manuel Dufoo Olvera" de la Secretaría de Salud de Ciudad de México del 1° de enero de 2014 al 30 de junio del 2017. La clasificación divide las fracturas múltiples como contiguas y no contiguas, acorde al número de cuerpos afectados y el nivel.. El análisis estadístico se realizó utilizando fórmulas de estadística descriptiva, para después tabular y graficar la información, para evaluar la relación entre la clasificación anatómica y el grado de lesión neurológica. Resultados: Fueron observados 530 pacientes, de los cuales 47 presentaron los criterios necesarios. Treinta y un pacientes (65,95%) del estudio fueron clasificados con fracturas contiguas y 16 casos (34,05%) con no contiguas. Catorce pacientes (29,78%) fueron clasificados con integridad neurológica ASIA D, 20 pacientes (42,58%) presentaron lesión completa ASIA A, siete pacientes (14,89%) en ASIA B y seis pacientes (12,76%) con lesión incompleta ASIA C. Conclusiones: La correlación entre la clasificación de lesión de columna vertebral y la presencia de lesión neurológica no mostró diferencias significativas entre fracturas contiguas y no contiguas. Nivel de Evidencia II; Retrospectivo.

Rewiring of auxin signaling under persistent shade.

Light cues from neighboring vegetation rapidly initiate plant shade-avoidance responses. Despite our detailed knowledge of the early steps of this response, the molecular events under prolonged shade are largely unclear. Here we show that persistent neighbor cues reinforce growth responses in addition to promoting auxin-responsive gene expression in Arabidopsis and soybean. However, while the elevation of auxin levels is well established as an early event, in Arabidopsis, the response to prolonged shade occurs when auxin levels have declined to the prestimulation values. Remarkably, the sustained low activity of phytochrome B under prolonged shade led to (i) decreased levels of PHYTOCHROME INTERACTING FACTOR 4 (PIF4) in the cotyledons (the organs that supply auxin) along with increased levels in the vascular tissues of the stem, (ii) elevated expression of the PIF4 targets INDOLE-3-ACETIC ACID 19 (IAA19) and IAA29, which in turn reduced the expression of the growth-repressive IAA17 regulator, (iii) reduced abundance of AUXIN RESPONSE FACTOR 6, (iv) reduced expression of MIR393 and increased abundance of its targets, the auxin receptors, and (v) elevated auxin signaling as indicated by molecular markers. Mathematical and genetic analyses support the physiological role of this system-level rearrangement. We propose that prolonged shade rewires the connectivity between light and auxin signaling to sustain shade avoidance without enhanced auxin levels.