Usefulness of the MS-MLPA technique in the diagnosis of Beckwith-Wiedemann syndrome and Silver-Russell syndrome.

INTRODUCTION: Epigenetic and genomic imprinting alterations of the 11p15.5 region cause excessive or deficient growth, which result in Beckwith-Wiedemann syndrome (BWS) or Silver-Russell syndrome (SRS), respectively. OBJECTIVE: To evaluate the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) methylation analysis technique in the diagnosis of BWS and SRS. METHODS: 11p15.5 methylation and variants were evaluated in patients with clinical diagnosis of BWS and SRS using the MS-MLPA technique in peripheral blood DNA. RESULTS: Paternal uniparental disomy and loss of maternal IC2 methylation were identified in two patients with BWS who had omphalocele and macroglossia, respectively. Paternal IC1hypomethylation was recorded in two patients with SRS of classic phenotype. CONCLUSIONS: Adequate genotype-phenotype correlation was observed with the methylation defects that were identified, which confirms the usefulness of MLPA as a first-line study in patients diagnosed with BWS and SRS.

INTRODUCCIÓN: Las alteraciones epigenéticas y genómicas de la región improntada 11p15.5 producen crecimiento excesivo o deficiente, que se manifiesta como síndrome de Beckwith-Wiedemann o síndrome de Silver-Russell, respectivamente. OBJETIVO: Evaluar la técnica de análisis de metilación MLPA (MS-MLPA, methylation-specific multiplex ligation-dependent probe amplification) en el diagnóstico de los síndromes de Beckwith-Wiedemann y de Silver-Russell. MÉTODOS: Se evaluó la metilación y las variantes de 11p15.5 en pacientes con diagnóstico clínico de síndrome de Beckwith-Wiedemann y síndrome de Silver-Russell mediante la técnica MS-MLPA en ADN de sangre periférica. RESULTADOS: Se identificó disomía uniparental paterna y pérdida de metilación del IC2 materno en dos pacientes con síndrome de Beckwith-Wiedemann, quienes presentaron onfalocele y macroglosia, respectivamente. Se registró hipometilación paterna del IC1 en dos pacientes con síndrome de Silver-Russell de fenotipo clásico. CONCLUSIONES: Se observó adecuada correlación genotipo-fenotipo con los defectos de metilación encontrados, lo que confirma la utilidad del MLPA como estudio de primera línea en pacientes con diagnóstico de síndrome de Beckwith-Wiedemann y síndrome de Silver-Russell.

Utilidad de la técnica de MS-MLPA en el diagnóstico de los síndromes de Beckwith-Wiedemann y Silver-Russell / Usefulness of the MS-MLPA technique in the diagnosis of Beckwith-Wiedemann syndrome and Silver-Russell syndrome

Resumen Introducción: Las alteraciones epigenéticas y genómicas de la región improntada 11p15.5 producen crecimiento excesivo o deficiente, que se manifiesta como síndrome de Beckwith-Wiedemann o síndrome de Silver-Russell, respectivamente. Objetivo: Evaluar la técnica de análisis de metilación MLPA (MS-MLPA, methylation-specific multiplex ligation-dependent probe amplification) en el diagnóstico de los síndromes de Beckwith-Wiedemann y de Silver-Russell. Métodos: Se evaluó la metilación y las variantes de 11p15.5 en pacientes con diagnóstico clínico de síndrome de Beckwith-Wiedemann y síndrome de Silver-Russell mediante la técnica MS-MLPA en ADN de sangre periférica. Resultados: Se identificó disomía uniparental paterna y pérdida de metilación del IC2 materno en dos pacientes con síndrome de Beckwith-Wiedemann, quienes presentaron onfalocele y macroglosia, respectivamente. Se registró hipometilación paterna del IC1 en dos pacientes con síndrome de Silver-Russell de fenotipo clásico. Conclusiones: Se observó adecuada correlación genotipo-fenotipo con los defectos de metilación encontrados, lo que confirma la utilidad del MLPA como estudio de primera línea en pacientes con diagnóstico de síndrome de Beckwith-Wiedemann y síndrome de Silver-Russell.

Abstract Introduction: Epigenetic and genomic imprinting alterations of the 11p15.5 region cause excessive or deficient growth, which result in Beckwith-Wiedemann syndrome (BWS) or Silver-Russell syndrome (SRS), respectively. Objective: To evaluate the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) methylation analysis technique in the diagnosis of BWS and SRS. Methods: 11p15.5 methylation and variants were evaluated in patients with clinical diagnosis of BWS and SRS using the MS-MLPA technique in peripheral blood DNA. Results: Paternal uniparental disomy and loss of maternal IC2 methylation were identified in two patients with BWS who had omphalocele and macroglossia, respectively. Paternal IC1hypomethylation was recorded in two patients with SRS of classic phenotype. Conclusions: Adequate genotype-phenotype correlation was observed with the methylation defects that were identified, which confirms the usefulness of MLPA as a first-line study in patients diagnosed with BWS and SRS.

Síndrome de Silver-Russell: Características clínicas, de neurodesenvolvimento e comunicação: Estudo de casos clínicos / Silver-Russell syndrome: clinical, neurodevelopmental and communication characteristics: clinical case studies

RESUMO A Síndrome de Silver Russel (SSR) é uma condição geneticamente heterogênea com fenótipo clínico que inclui restrição do crescimento intrauterino e pós-natal, alterações craniofaciais, assimetrias corporais, baixo índice de massa corporal e dificuldades alimentares. Há expectativa de alterações do desenvolvimento motor, da coordenação global e de fala. O presente estudo tem como objetivo apresentar características da síndrome, do neurodesenvolvimento e comunicação de três crianças do sexo masculino, com diagnóstico da síndrome, na faixa etária de 16, 18 e 44 meses, respectivamente. Cumpriram-se os critérios éticos. Foi realizada análise de prontuário, com objetivo de coletar informações da anamnese realizada com os responsáveis, e da avaliação realizada com as crianças. A avaliação foi realizada por meio da aplicação dos seguintes instrumentos: Observação do Comportamento Comunicativo (OCC), Teste de Screening de Desenvolvimento Denver-II (TSDD-II) e o Early Language Milestone Scale (ELMS). O levantamento de características confirmou a hipótese da SSR; na OCC verificou-se atraso nos comportamentos comunicativos para todos os participantes; no TSDD-II verificou-se atraso nas habilidades motora grossa, motora fina-adaptativa, linguagem e pessoal social. Na ELM verificou-se escores aquém do esperado para as funções auditiva receptiva e auditiva expressiva com habilidades receptivas mais desenvolvidas do que as habilidades expressivas. A SSR merece ser reconhecida pela comunidade científica, uma vez que as características fenotípicas e os dados de vida pregressa, possibilitam que seja levantada a hipótese da síndrome, visando o diagnóstico correto precocemente e um planejamento terapêutico que minimize os efeitos deletérios desta condição.

ABSTRACT Silver Russell Syndrome (SRS) is a genetically heterogeneous condition with a clinical phenotype that includes intrauterine and postnatal growth restriction, craniofacial alterations, body asymmetries, low body mass index, and feeding difficulties. Alterations in motor development, global coordination, and speech are expected. The current study aims to present the syndrome, neurodevelopment, and communication characteristics of three male children diagnosed with the syndrome, aged 16, 18, and 44 months, respectively. Ethical principles were followed. An analysis of the medical records, aiming to collect information of the anamnesis, conducted with the guardians, and of the assessment carried out with the children was performed. The assessment was performed by applying the following instruments: Communicative Behavior Observation (CBO), Development Screening Test Denver-II (TSDD-II), and the Early Language Milestone Scale (ELMS). The survey of characteristics confirmed the SRS hypothesis; it was verified a delay in communicative behavior for all participants in CBO; in TSDD-II there was a delay in gross motor, fine motor-adaptive, language, and social personal skills. Scores below expectations were found for receptive auditory and expressive auditory functions, with receptive abilities more developed than expressive abilities, in ELM. The SRS deserves to be recognized by the scientific community, since the phenotypic characteristics and the data from the previous life allow the hypothesis of the syndrome to be raised, aiming at an early correct diagnosis and therapeutic planning that minimizes the harmful effects of this condition.

Síndrome de Silver-Russell. Aspectos clínicos y etiopatológicos de una entidad ejemplo de impronta genómica / Silver-Russell syndrome. Clinical and etiopathological aspects of a model genomic imprinting entity

El síndrome de Silver-Russell se caracteriza por retraso del crecimiento intrauterino asimétrico, con circunferencia craneal normal, barbilla pequeña y puntiaguda, que proporciona un aspecto de rostro triangular. Puede, además, presentar asimetría corporal, entre otros. Tiene una incidencia mundial estimada de 1 en 30 000-100 000 nacimientos, aunque este número es, probablemente, subestimado. En alrededor del 60 % de los casos, se puede identificar una causa molecular y la principal es la hipometilación del alelo paterno en la región de control de impresión 1 localizado en 11p15.5-p15.4. Realizar el diagnóstico de esta entidad, excluir los diagnósticos diferenciales y conocer las correlaciones (epi)genotipo-fenotipo son necesarios para realizar el adecuado seguimiento, brindar las opciones terapéuticas disponibles y el oportuno asesoramiento genético familiar. El objetivo del presente artículo es mostrar el estado actual del síndrome de Silver-Russell, un ejemplo de trastorno de impronta genómica.

Silver-Russell syndrome is characterized by asymmetrical intrauterine growth retardation, with normal head circumference and small, pointed chin, which results in a triangular face. It can also include body asymmetry, among other characteristics. Its global incidence is estimated at 1 in 30 000-100 000 births, even though this figure may be underestimated. In approximately 60 % of cases, a molecular cause can be identified, and the main one is hypomethylation of the paternal allele at the imprinting control region 1 located at 11p15.5-p15.4. It is necessary to make the diagnosis of this entity, exclude differential diagnoses, and know (epi)genotype-phenotype correlations in order to ensure an adequate follow-up, provide available therapeutic options, and offer a timely family genetic counseling. The objective of this article is to describe the current status of the Silver-Russell syndrome, a model of genomic imprinting disorder.

Silver-Russell syndrome. Clinical and etiopathological aspects of a model genomic imprinting entity. / Síndrome de Silver-Russell. Aspectos clínicos y etiopatológicos de una entidad ejemplo de impronta genómica.

Silver-Russell syndrome is characterized by asymmetrical intrauterine growth retardation, with normal head circumference and small, pointed chin, which results in a triangular face. It can also include body asymmetry, among other characteristics. Its global incidence is estimated at 1 in 30 000-100 000 births, even though this figure may be underestimated. In approximately 60 % of cases, a molecular cause can be identified, and the main one is hypomethylation of the paternal allele at the imprinting control region 1 located at 11p15.5-p15.4. It is necessary to make the diagnosis of this entity, exclude differential diagnoses, and know (epi)genotype-phenotype correlations in order to ensure an adequate follow-up, provide available therapeutic options, and offer a timely family genetic counseling. The objective of this article is to describe the current status of the Silver-Russell syndrome, a model of genomic imprinting disorder.

El síndrome de Silver-Russell se caracteriza por retraso del crecimiento intrauterino asimétrico, con circunferencia craneal normal, barbilla pequeña y puntiaguda, que proporciona un aspecto de rostro triangular. Puede, además, presentar asimetría corporal, entre otros. Tiene una incidencia mundial estimada de 1 en 30 000- 100 000 nacimientos, aunque este número es, probablemente, subestimado. En alrededor del 60 % de los casos, se puede identificar una causa molecular y la principal es la hipometilación del alelo paterno en la región de control de impresión 1 localizado en 11p15.5-p15.4. Realizar el diagnóstico de esta entidad, excluir los diagnósticos diferenciales y conocer las correlaciones (epi)genotipo-fenotipo son necesarios para realizar el adecuado seguimiento, brindar las opciones terapéuticas disponibles y el oportuno asesoramiento genético familiar. El objetivo del presente artículo es mostrar el estado actual del síndrome de Silver-Russell, un ejemplo de trastorno de impronta genómica.

Singlet oxygen generation by the reaction of acrolein with peroxynitrite via a 2-hydroxyvinyl radical intermediate.

Acrolein (2-propenal) is an environmental pollutant, food contaminant, and endogenous toxic by-product formed in the thermal decomposition and peroxidation of lipids, proteins, and carbohydrates. Like other α,ß-unsaturated aldehydes, acrolein undergoes Michael addition of nucleophiles such as basic amino acids residues of proteins and nucleobases, triggering aging associated disorders. Here, we show that acrolein is also a potential target of the potent biological oxidant, nitrosating and nitrating agent peroxynitrite. In vitro studies revealed the occurrence of 1,4-addition of peroxynitrite (k2 = 6 × 103 M-1 s-1, pH 7.2, 25 °C) to acrolein in air-equilibrated phosphate buffer. This is attested by acrolein concentration-dependent oxygen uptake, peroxynitrite consumption, and generation of formaldehyde and glyoxal as final products. These products are predicted to be originated from the Russell termination of •OOCH=CH(OH) radical which also includes molecular oxygen at the singlet delta state (O21Δg). Accordingly, EPR spin trapping studies with the 2,6-nitrosobenzene-4-sulfonate ion (DBNBS) revealed a 6-line spectrum attributable to the 2-hydroxyvinyl radical adduct. Singlet oxygen was identified by its characteristic monomolecular IR emission at 1,270 nm in deuterated buffer, which was expectedly quenched upon addition of water and sodium azide. These data represent the first report on singlet oxygen creation from a vinylperoxyl radical, previously reported for alkyl- and formylperoxyl radicals, and may contribute to better understand the adverse acrolein behavior in vivo.

Proteomics and antivenom immunoprofiling of Russell's viper (Daboia siamensis) venoms from Thailand and Indonesia.

The Eastern Russell's viper, Daboia siamensis, is a WHO Category 1 medically important venomous snake. It has a wide but disjunct distribution in Southeast Asia. The specific antivenom, D. siamensis Monovalent Antivenom (DsMAV-Thailand) is produced in Thailand but not available in Indonesia, where a heterologous trivalent antivenom, Serum Anti Bisa Ular (SABU), is used instead. This study aimed to investigate the geographical venom variation of D. siamensis from Thailand (Ds-Thailand) and Indonesia (Ds-Indonesia), and the immunorecognition of the venom proteins by antivenoms. METHODS: The venom proteins were decomplexed with reverse-phase high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by in-solution tryptic digestion, nano-liquid chromatography-tandem mass spectrometry and protein identification. The efficacies of DsMAV-Thailand and SABU in binding the various venom fractions were assessed using an enzyme-linked immunosorbent assay optimized for immunorecognition profiling. RESULTS: The two most abundant protein families in Ds-Thailand venom are phospholipase A2 (PLA2) and Kunitz-type serine protease inhibitor (KSPI). Those abundant in Ds-Indonesia venom are PLA2 and serine protease. KSPI and vascular endothelial growth factor were detected in Ds-Thailand venom, whereas L-amino acid oxidase and disintegrin were present in Ds-Indonesia venom. Common proteins shared between the two included snaclecs, serine proteases, metalloproteinases, phosphodiesterases, 5'nucleotidases and nerve growth factors at varying abundances. DsMAV-Thailand exhibited strong immunorecognition of the major protein fractions in both venoms, but low immunoreactivity toward the low molecular weight proteins e.g. KSPI and disintegrins. On the other hand, SABU was virtually ineffective in binding all fractionated venom proteins. CONCLUSION: D. siamensis venoms from Thailand and Indonesia varied geographically in the protein subtypes and abundances. The venoms, nevertheless, shared conserved antigenicity that allowed effective immunorecognition by DsMAV-Thailand but not by SABU, consistent with the neutralization efficacy of the antivenoms. A specific, appropriate antivenom is needed in Indonesia to treat Russell's viper envenomation.

Proteomics and antivenom immunoprofiling of Russell's viper (Daboia siamensis) venoms from Thailand and Indonesia

Background The Eastern Russells viper, Daboia siamensis, is a WHO Category 1 medically important venomous snake. It has a wide but disjunct distribution in Southeast Asia. The specific antivenom, D. siamensis Monovalent Antivenom (DsMAV-Thailand) is produced in Thailand but not available in Indonesia, where a heterologous trivalent antivenom, Serum Anti Bisa Ular (SABU), is used instead. This study aimed to investigate the geographical venom variation of D. siamensis from Thailand (Ds-Thailand) and Indonesia (Ds-Indonesia), and the immunorecognition of the venom proteins by antivenoms. Methods: The venom proteins were decomplexed with reverse-phase high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by in-solution tryptic digestion, nano-liquid chromatography-tandem mass spectrometry and protein identification. The efficacies of DsMAV-Thailand and SABU in binding the various venom fractions were assessed using an enzyme-linked immunosorbent assay optimized for immunorecognition profiling. Results: The two most abundant protein families in Ds-Thailand venom are phospholipase A2 (PLA2) and Kunitz-type serine protease inhibitor (KSPI). Those abundant in Ds-Indonesia venom are PLA2 and serine protease. KSPI and vascular endothelial growth factor were detected in Ds-Thailand venom, whereas L-amino acid oxidase and disintegrin were present in Ds-Indonesia venom. Common proteins shared between the two included snaclecs, serine proteases, metalloproteinases, phosphodiesterases, 5nucleotidases and nerve growth factors at varying abundances. DsMAV-Thailand exhibited strong immunorecognition of the major protein fractions in both venoms, but low immunoreactivity toward the low molecular weight proteins e.g. KSPI and disintegrins. On the other hand, SABU was virtually ineffective in binding all fractionated venom proteins. Conclusion: D. siamensis venoms from Thailand and Indonesia varied...(AU)

Proteomics and antivenom immunoprofiling of Russell's viper (Daboia siamensis) venoms from Thailand and Indonesia

The Eastern Russell's viper, Daboia siamensis, is a WHO Category 1 medically important venomous snake. It has a wide but disjunct distribution in Southeast Asia. The specific antivenom, D. siamensis Monovalent Antivenom (DsMAV-Thailand) is produced in Thailand but not available in Indonesia, where a heterologous trivalent antivenom, Serum Anti Bisa Ular (SABU), is used instead. This study aimed to investigate the geographical venom variation of D. siamensis from Thailand (Ds-Thailand) and Indonesia (Ds-Indonesia), and the immunorecognition of the venom proteins by antivenoms. Methods: The venom proteins were decomplexed with reverse-phase high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by in-solution tryptic digestion, nano-liquid chromatography-tandem mass spectrometry and protein identification. The efficacies of DsMAV-Thailand and SABU in binding the various venom fractions were assessed using an enzyme-linked immunosorbent assay optimized for immunorecognition profiling. Results: The two most abundant protein families in Ds-Thailand venom are phospholipase A2 (PLA2) and Kunitz-type serine protease inhibitor (KSPI). Those abundant in Ds-Indonesia venom are PLA2 and serine protease. KSPI and vascular endothelial growth factor were detected in Ds-Thailand venom, whereas L-amino acid oxidase and disintegrin were present in Ds-Indonesia venom. Common proteins shared between the two included snaclecs, serine proteases, metalloproteinases, phosphodiesterases, 5'nucleotidases and nerve growth factors at varying abundances. DsMAV-Thailand exhibited strong immunorecognition of the major protein fractions in both venoms, but low immunoreactivity toward the low molecular weight proteins e.g. KSPI and disintegrins. On the other hand, SABU was virtually ineffective in binding all fractionated venom proteins. Conclusion: D. siamensis venoms from Thailand and Indonesia varied geographically in the protein subtypes and abundances. The venoms, nevertheless, shared conserved antigenicity that allowed effective immunorecognition by DsMAV-Thailand but not by SABU, consistent with the neutralization efficacy of the antivenoms. A specific, appropriate antivenom is needed in Indonesia to treat Russell's viper envenomation.(AU)

Stability of the hypocotyl length of soybean cultivars using neural networks and traditional methods / Estabilidade do comprimento do hipocótilo de plantas de cultivares de soja por meio de redes neurais e metodologias tradicionais

The length of the hypocotyl has been highlighted as a potential descriptor of the soybean crop. However, there is no information available in the published literature about its behavior over several planting times. The present study aimed to identify soybean cultivars with stability and predictability of hypocotyl length behavior through neural networks and traditional adaptability and stability methodologies. We analyzed 16 soybean cultivars in 6 planting seasons under greenhouse conditions. In each season, a randomized block design with 4 replications was adopted. The experimental unit was composed of 3 plants. The plot mean was used in the analysis. Hypocotyl length data were analyzed by analysis of variance and Tukeys test. Then analyses were carried out using the Traditional Method, Plaisted and Peterson, Wricke, Eberhart and Russell, and Artificial Neural Networks. A significant effect (p<0.01 by the F test) was identified for Cultivars versus Planting Season and Planting Seasons and Cultivars. Cultivars BRS810C, BRSMG760SRR, TMG1175RR, and BMX Tornado RR showed lower averages, high stability, and general adaptability regarding soybean hypocotyl length whereas the cultivar BG4272 presented higher mean, high stability, and general adaptability. Identification of soybean cultivars of predictable and stable behavior as to hypocotyl length contributes to Soybean Improvement as it further our knowledge on the potential descriptor and the possibility of increasing the number of descriptors.(AU)

O comprimento do hipocótilo tem-se destacado como potencial descritor da cultura da soja, no entanto, não se tem informação sobre o seu comportamento ao longo de várias épocas de plantio. Diante disto, objetivou-se identificar cultivares de soja com estabilidade e previsibilidade de comportamento quanto ao comprimento do hipocótilo por meio de redes neurais e metodologias tradicionais de adaptabilidade e estabilidade. Analisou-se 16 cultivares de soja em seis épocas de plantio, em condições de casa de vegetação. Em cada época, adotou-se o delineamento em blocos casualizados com quatro repetições, sendo a unidade experimental composta por três plantas e usou-se a média da parcela na análise. Os dados de comprimento de hipocótilo foram analisados por meio da análise de variância e teste de Tukey e, posteriormente, procedeu-se análises por meio do Método Tradicional, Plaisted e Peterson, Wricke, Eberhart e Russell e Redes Neurais Artificiais. Identificou-se efeito significativo (p<0,01 pelo teste F) para Cultivares x Épocas, Épocas e Cultivares. As cultivares BRS810C, BRSMG760SRR, TMG1175RR e BMX Tornado RR apresentaram menores médias, alta estabilidade e adaptabilidade geral quanto ao comprimento do hipocótilo de soja; enquanto que, a cultivar BG4272 apresentou maior média, alta estabilidade e adaptabilidade geral. A identificação de cultivares de soja de comportamento previsível e estável, quanto ao comprimento do hipocótilo, contribui para o Melhoramento da Soja no tocante ao melhor conhecimento do potencial descritor e à possibilidade de incremento do número de descritores.(AU)

Stability of the hypocotyl length of soybean cultivars using neural networks and traditional methods / Estabilidade do comprimento do hipocótilo de plantas de cultivares de soja por meio de redes neurais e metodologias tradicionais

ABSTRACT: The length of the hypocotyl has been highlighted as a potential descriptor of the soybean crop. However, there is no information available in the published literature about its behavior over several planting times. The present study aimed to identify soybean cultivars with stability and predictability of hypocotyl length behavior through neural networks and traditional adaptability and stability methodologies. We analyzed 16 soybean cultivars in 6 planting seasons under greenhouse conditions. In each season, a randomized block design with 4 replications was adopted. The experimental unit was composed of 3 plants. The plot mean was used in the analysis. Hypocotyl length data were analyzed by analysis of variance and Tukey's test. Then analyses were carried out using the Traditional Method, Plaisted and Peterson, Wricke, Eberhart and Russell, and Artificial Neural Networks. A significant effect (p<0.01 by the F test) was identified for Cultivars versus Planting Season and Planting Seasons and Cultivars. Cultivars BRS810C, BRSMG760SRR, TMG1175RR, and BMX Tornado RR showed lower averages, high stability, and general adaptability regarding soybean hypocotyl length whereas the cultivar BG4272 presented higher mean, high stability, and general adaptability. Identification of soybean cultivars of predictable and stable behavior as to hypocotyl length contributes to Soybean Improvement as it further our knowledge on the potential descriptor and the possibility of increasing the number of descriptors.

RESUMO: O comprimento do hipocótilo tem-se destacado como potencial descritor da cultura da soja, no entanto, não se tem informação sobre o seu comportamento ao longo de várias épocas de plantio. Diante disto, objetivou-se identificar cultivares de soja com estabilidade e previsibilidade de comportamento quanto ao comprimento do hipocótilo por meio de redes neurais e metodologias tradicionais de adaptabilidade e estabilidade. Analisou-se 16 cultivares de soja em seis épocas de plantio, em condições de casa de vegetação. Em cada época, adotou-se o delineamento em blocos casualizados com quatro repetições, sendo a unidade experimental composta por três plantas e usou-se a média da parcela na análise. Os dados de comprimento de hipocótilo foram analisados por meio da análise de variância e teste de Tukey e, posteriormente, procedeu-se análises por meio do Método Tradicional, Plaisted e Peterson, Wricke, Eberhart e Russell e Redes Neurais Artificiais. Identificou-se efeito significativo (p<0,01 pelo teste F) para Cultivares x Épocas, Épocas e Cultivares. As cultivares BRS810C, BRSMG760SRR, TMG1175RR e BMX Tornado RR apresentaram menores médias, alta estabilidade e adaptabilidade geral quanto ao comprimento do hipocótilo de soja; enquanto que, a cultivar BG4272 apresentou maior média, alta estabilidade e adaptabilidade geral. A identificação de cultivares de soja de comportamento previsível e estável, quanto ao comprimento do hipocótilo, contribui para o Melhoramento da Soja no tocante ao melhor conhecimento do potencial descritor e à possibilidade de incremento do número de descritores.

Síndrome de Silver-Russell, un desafío diagnóstico / Silver-russell syndrome, a diagnostic challenge

El síndrome de Silver-Russell es una condición infrecuente que clínicamente se manifiesta por macrocefalia relativa, dismorfias faciales, restricción importante de crecimiento pre-y postnatal y otros hallazgos variables al examen físico. En un 60% de los pacientes el estudio genético actualmente disponible permite establecer el diagnostico, sin embargo prevalecen los criterios clínicos. Se presenta el caso clínico de un paciente evaluado al año de vida con historia de restricción de crecimiento prenatal y con talla baja y desnutrición crónica descompensada, en el cuál se descartaron otras etiologías y se concluye por criterios clínicos de padecer el síndrome, a pesar de un estudio genético negativo. Debido a un amplio espectro de manifestaciones clínicas a veces sutiles y confundentes se debe conocer este síndrome para su diagnóstico oportuno.

Silver-Russell syndrome is an uncommon condition that manifests itself as relative macrocephaly, facial dysmorphia, poor pre-and post-natal growth and other variable physical features. In 60% of patients it is possible to establish the diagnosis through available genetic testing; however, clinical criteria are more important. We present the clinical case of a patient with poor pre-natal growth, small size and chronic malnutrition evaluated at one year old where other etiologies were discounted and the syndrome diagnosed because of the clinical signs, despite genetic tests being negative. With its ample spectrum of sometimes subtle and confusing clinical signs, familiarity with this syndrome is key to reaching an early diagnosis.

Perfil Nutricional de Crianças Portadoras de Tumores Cerebrais com Síndrome Diencefálica ou Síndrome de Russell recebendo Dieta Enteral / Nutritional Profile of Children with Brain Tumor with Diencephalic Syndrome or Russell Syndrome receiving Enteral Diet / Perfil Nutricional de Niños Portadores de Tumores Cerebrales con Síndrome diencefálico o Síndrome de Russell recibiendo dieta Enteral

Introdução: a síndrome diencefálica é uma doença pediátrica rara, decorrente de tumores hipotalâmicos, caracterizada por failure to thrive. Objetivo: descrever o estado nutricional e a terapia nutricional por meio de sonda nasoenteral de pacientes com tumores cerebrais com a síndrome diencefálica. Método:sete pacientes foram acompanhados de julho/1999 a abril/2002 e analisados retrospectivamente, usando os escores-z de peso para idade (P/i), peso para estatura (P/e) e estatura para idade (e/i) no diagnóstico da desnutrição. todos foram avaliados por meio de composição corporal: prega cutânea triciptal (Pct) e circunferências do braço e muscular do braço (cB e cMB) e receberam alimentação por sonda nasoenteral ou gastrostomia após o diagnóstico da neoplasia. Resultados: a idade variou de 2 meses a 13 anos, cinco do sexo masculino. a duração média da nutrição enteral foi de 7 meses (1,1-18,5) após o diagnóstico, sem diferença estatística significante na evolução dos escores-z, apesar do aumento nas médias de P/i (-4,42 para -3,50) e P/e (-3,06 para -1,99), e dos indicadores de composição corporal (Pct: 2,85 para 4,88; cB: 9,81 para 11,84 e cMB: 8,91 para 10,31). Houve redução na média da e/i, caracterizando o atraso no crescimento dessas crianças. Conclusão: a nutrição enteral demonstrou garantir a oferta nutricional e recuperar em parte os indicadores nutricionais de desnutrição aguda; principalmente a gordura corporal, mais do que massa magra. entretanto, manteve-se o déficit de crescimento, agravado na maioria dos casos. a terapia nutricional deve ser implantada durante o tratamento oncológico, assegurando sua continuidade.

Introduction:diencephalic syndrome is a rare disorder of infancy characterized by profound emaciation with failure to thrive. The majority of cases of the syndrome are due to low grade gliomas of the anterior hypothalamus or optic nerve. Objective:to report the nutritional status and efficacy of nutritional support in patients with brain tumors that developed the russell's syndrome. Method:seven patients were retrospectively evaluated by means of z-score of the weight for age (W/a), weight for height (W/H) and height for age (H/a) nutritional status index, for protein-energy malnutrition diagnosis. They were evaluated by means of triceps skinfold thickness (tsFt), arm circumferences (ac) and muscle arm circumferences (Mac) and received enteral nutrition, by nasoenteral tube or gastrostomy at cancer diagnostic. Results: The ages ranged from 2 months to 13 years, five children were males. Mean of the nutritional support was 7 months (1.1-18.5 months) after diagnostic, without statistical differences in z-scores evolution, but there are increase in averages of the W/a (-4,42 to -3,50) and W/H (-3,06 to -1,99), and body composition indicators (tsFt): 2.85 to 4.88, ac: 9.81 to 11.84 and Mac: 8.91 to 10.31). There was decreased in average of H/a, evidencing the growth arrest of these children. Conclusion:enteral feeding has been shown to guarantee nutritional supply and to partially recover nutritional indicators of acute malnutrition; especially body fat, rather than lean mass. However, the growth deficit was not corrected, being aggravated in most cases. nutritional support should be implanted during oncological treatment, ensuring its maintenance.

Introducción:el síndrome diencefalica es una enfermedad pediátrica rara, derivada de tumores de la región hipotalámica, caracterizada por failure to thrive. Objetivo: describir condiciones nutricionales y terapia nutricional de pacientes con tumores cerebrales com síndrome diencefalica y nutrición enteral. Método: siete pacientes fueron acompañados de julio/1999 a abril/2002 y analizados retrospectivamente, usando el score-Z de peso para edad (P/i), peso para estatura (P/e) y estatura para edad (e/i) para el diagnóstico de la desnutrición. todos fueron evaluados por composición corporal (pliegue cutáneo triciptal y circunferencias del brazo y muscular del brazo). los pacientes recibieron nutrición enteral por sonda o gastrostomía, luego del diagnóstico de cancer. Resultados:la edad varía de 2 meses a 13 años, cinco del sexo masculino. la duración media de la nutrición enteral fue de 7 meses (1,1-18,5) después del diagnóstico. no hubo diferencia estadística en la evolución nutricional, a pesar del aumento en P/i (-4,42 a -3,50) y P/e (-3,06 a -1,99), así como en la composición corporal (Pct: 2,85 a 4,88, cB: 9,81 a 11,84 y cMB: 8,91 para 10.31). Hubo una reducción de e/i, caracterizando el retraso en el crecimiento. Conclusión:la nutrición enteral demostró garantizar la oferta nutricional.e la recuperación parcial de la desnutrición aguda, principalmente grasa corporal, más que masa magra, sin respuesta al déficit en el crecimiento, que se agravó en casi todos los casos. la terapia nutricional debe ser implantada durante el tratamiento oncológico, asegurando su continuidad.

Chronic gastrointestinal inflammation in a dog mimicking human russell body gastroduodenitis

Herein we describe an unusual benign chronic gastroduodenal inflammation associated with protein losing enteropathy in a dog. A 10-year-old Golden Retriever dog was presented for chronic weight loss associated with pica, ptyalism, vomiting and diarrhea. Blood chemistry showed hypoproteinaemia and hypoalbuminaemia. Gastric and duodenal full-thickness biopsies were collected and histopathological examination revealed severe mucosal infiltration with Mott cells, consistent with Russell body gastroduodenitis in humans. Warthin-starry stain showed no Helicobacterspp. proliferation in gastric biopsies. After treatment includinganti-acid, antibiotics and corticosteroids, no recurrence of gastrointestinal signs was reported and improvement in clinical and biological condition was observed.(AU)

Comparison of different laboratory tests in the evaluation of hemorrhagic risk of patients using rivaroxaban in the critical care setting: diagnostic accuracy study.

BACKGROUND: Rivaroxaban is a direct oral anticoagulant designed to dispense with the necessity of laboratory monitoring. However, monitoring rivaroxaban levels is necessary in certain clinical conditions, especially in the critical care setting. METHODS: This is a diagnostic accuracy study evaluating sensitivity and specificity of prothrombin time (PT), activated partial thromboplastin time (aPTT), and Dilute Russell viper venom time (dRVVT), to evaluate the hemorrhagic risk in patients taking rivaroxaban. The study used a convenience sample of 40 clinically stable patients using rivaroxaban to treat deep vein thrombosis or atrial fibrillation admitted in a private hospital in Brazil, compared to a group of 60 healthy controls. The samples from patients were collected two hours after the use of the medication (peak) and two hours before the next dose (trough). RESULTS: The correlation with the plasmatic concentration measured by anti-FXa assay was higher for PT and dRVVTS. The PT and aPTT tests presented higher specificity, while dRVVT was 100% sensible. CONCLUSIONS: There was a strong correlation between the tests and the plasma concentration of the drug. Additionally, our results demonstrated the potential use of dRVVT as a screening test in the emergency room and the need of a second test to improve specificity.

Chronic gastrointestinal inflammation in a dog mimicking human russell body gastroduodenitis

Herein we describe an unusual benign chronic gastroduodenal inflammation associated with protein losing enteropathy in a dog. A 10-year-old Golden Retriever dog was presented for chronic weight loss associated with pica, ptyalism, vomiting and diarrhea. Blood chemistry showed hypoproteinaemia and hypoalbuminaemia. Gastric and duodenal full-thickness biopsies were collected and histopathological examination revealed severe mucosal infiltration with Mott cells, consistent with Russell body gastroduodenitis in humans. Warthin-starry stain showed no Helicobacterspp. proliferation in gastric biopsies. After treatment includinganti-acid, antibiotics and corticosteroids, no recurrence of gastrointestinal signs was reported and improvement in clinical and biological condition was observed.

A new large Myloplus Gill 1896 from rio Negro basin, Brazilian Amazon (Characiformes: Serrasalmidae).

Myloplus lucienae, new species, is described from the blackwater tributaries of the rio Negro basin. It is one of the few Myloplus species typically found in rapid areas of the Guiana Shield. It is diagnosed from congeners by the combination of an elongated body, small prepelvic spines that reach anteriorly just to the middle of the abdomen between verticals through pectoral- and pelvic-fin origin, and large scales on flanks resulting in smaller scale counts.

Dabigatran en plasma: tiempos de trombina diluido, Ecarin y veneno de víbora de Russell diluido / Plasma dabigatran: diluted thrombin time, Ecarin and diluted Russell Viper Venom Time / Dabigatrana em plasma: tempos de trombina diluído, Ecarin e veneno de víbora de Russell diluído

Los objetivos del trabajo fueron verificar la calidad analítica del ensayo tiempo de trombina diluido (DTI) para medición de la concentración plasmática (cc) de dabigatran comparando dos coagulómetros de detección foto-óptica, comparar los resultados con el tiempo de Ecarin (ECT) y correlacionar las cc con las pruebas básicas de coagulación Tiempo de protrombina (TP), APTT y Tiempo de trombina (TT), y tiempo de veneno de víbora de Russell con fosfolípidos concentrados (DRVVTC). Se tomaron 43 muestras de plasma en el valle (10-14 h de la última toma) de 40 pacientes que recibían dabigatran. DTI y ECT presentaron (%) repetitividad <5,4% y <7,5%, CV interensayo <6% y <9%, respectivamente, en el protocolo EP15A2, aceptables para un Error Total permitido (TEa) <15%. Las cc medidas en pacientes fueron: mediana 83 (4-945) ng/mL. La comparación de equipos ACL TOP 300 y 500 dio resultados equivalentes por procedimiento alternativo de comparación de métodos. La comparación ECT vs. DTI fue satisfactoria por regresión de Deming (pendiente 1,143, ordenada al origen -19,33). Las correlaciones de cc vs. APTT, TP y DRVVTC fueron moderadas y no lineales tendiendo a plateau a cc>350 ng/mL, r2 0,59, 0,66 y 0,59, respectivamente. El TT fue extremadamente sensible: >120 s a cc 50 ng/mL. DTI presentó un buen desempeño analítico y permitió cuantificar dabigatran plasmático a cc bajas y altas en ambos equipos utilizados. ECT presentó resultados comparables a DTI. Se verifica una correlación moderada entre cc de dabigatran y las pruebas clásicas y DRVVTC, pudiendo ser estimadores de cc a partir de los 50 ng/mL.

The aims of the study were to verify the analytical performance of Dilute Thrombin Time (DTI) test to measure plasma dabigatran concentration (cc) in two photo-optical coagulometers, compare Ecarin clotting Time (ECT) and DTI results, and correlate cc with classical coagulation tests: prothrombin time (PT), APTT, thrombin time (TT) and diluted Russell Viper Venom Time tests with high phospholipid concentration (DRVVTC). Forty three plasma samples from 40 patients taking dabigatran were drown at through (10-14 hs.since last dose). DTI and ECT showed repetitivity (%) <5.4% and <7.5%, interassay CV <6% and <9%, respectively, following EP15A2 protocol, acceptable considering a Allowed Total Error (TEa)<15%. Patients` cc: median 83 (4-945) ng/mL. The comparison between ACL TOP 300 and 500 coagulometers showed equivalent results by using the alternative method comparison test. ECT vs. DTI: acceptable by Deming`s regression (slope 1.143, Y insert -19.33). cc vs. APTT, TP and DRVVTC: nonlinear and moderate correlations with plateau reached at cc >350 ng/mL, r2 0.59, 0.66 y 0.59, respectively. TT is extremely prolonged at cc >50 ng/mL. In conclusion: DTI showed a good analytical performance in both coagulometers. ECT showed comparable results to DTI. We verified that dabigatran cc presented moderate correlations with PT, APTT and DRVVTC, and that these tests could only qualitative estimate cc >50 ng/mL.

Os objetivos do trabalho foram verificar a qualidade analítica do ensaio tempo de trombina diluído (DTI) para medição da concentração plasmática (cc) de dabigatrana, comparando dois coagulômetros de detecção foto-óptica, comparar os resultados com o tempo de Ecarina (ECT) e correlacionar as cc com os testes básicos de coagulação Tempo de protrombina (TP), APTT e Tempo de trombina (TT), e tempo de veneno de víbora de Russell com fosfolipídios concentrados (DRVVTC). Foram tomadas 43 amostras de plasma no vale (10-14 h. da última toma) de 40 pacientes que recebiam dabigatrana. DTI e ECT apresentaram (%) repetitividade <5,4% e <7,5%, CV interensaio <6% e <9%, respectivamente, no protocolo EP15A2, aceitáveis para um Erro Total permitido (TEa) <15%. Cc medidas em pacientes: mediana 83 (4-945) ng/mL. Comparação de equipamentos ACL TOP 300 e 500: resultados equivalentes por procedimento alternativo de comparação de métodos. Comparação ECT vs. DTI: satisfatória por regressão de Deming (pendente 1,143, ordenada à origem -19,33). Correlações cc vs. APTT, TP e DRVVTC: moderadas e não lineares tendendo a plateau a cc>350 ng/mL, r2 0,59; 0,66 e 0,59, respectivamente. O TT é extremamente sensível: >120 s a cc 50 ng/mL. DTI apresentou um bom desempenho analítico e permitiu quantificar dabigatrana plasmática a cc baixas e altas em ambos os equipamentos utilizados. ECT apresentou resultados comparáveis com DTI. Verifica-se uma correlação moderada entre cc de dabigatrana e os testes clássicos e DRVVTC, podendo ser estimadores de cc a partir dos 50 ng/mL.

Are participants in markets for water rights more efficient in the use of water than non-participants? A case study for Limarí Valley (Chile).

The need to increase water productivity in agriculture has been stressed as one of the most important factors to achieve greater agricultural productivity and sustainability. The main aim of this paper is to investigate whether there are differences in water use efficiency (WUE) between farmers who participate in water markets and farmers who do not participate in them. Moreover, the use of a non-radial data envelopment analysis model allows to compute global efficiency (GE), WUE as well the efficiency in the use of other inputs such as fertilizers, pesticides, energy, and labor. In a second stage, external factors that may affect GE and WUE are explored. The empirical application focuses on a sample of farmers located in Limarí Valley (Chile) where regulated permanent water rights (WR) markets for surface water have a long tradition. Results illustrate that WR sellers are the most efficient in the use of water while non-traders are the farmers that present the lowest WUE. From a policy perspective, significant conclusions are drawn from the assessment of agricultural water productivity in the framework of water markets.

B cell lymphoma with mott cell differentiation in a dog

Background: B cell lymphoma with Mott cell differentiation is rarely reported in dogs. This neoplasms has been diagnosed in the gastrointestinal tract and therefore is considered the differential diagnosis of obstruction by foreign body, enteritis and other intestinal neoplasms. The objective of the present study was to describe macroscopic, microscopic and immunohistochemical findings of a B cell lymphoma with Mott cell differentiation in the gastrointestinal tract of a dog.Case: A 7-year-old male German Shepherd dog was referred to necropsy with a mass 12 cm in diameter in the ileum-cecocolic junction, compromising mesenteric lymph nodes. Cytology showed two types of lymphoid cells. Approximately 80-90% of cells were round, with large cytoplasm containing numerous basophilic inclusion corpuscles, round nuclei, condensed chromatin, inconspicuous nucleoli, moderate anisokaryosis and marked anisocytosis. The other cells were round, with scarce basophilic cytoplasm, round nuclei, condensed chromatin and inconspicuous nucleoli. Mild anisokaryosis and anisocytosis and mitotic figures were sometimes identified. Histology revealed the predominance of round cells, with large cytoplasm containing numerous eosinophilic corpuscles (Russel bodies). Neoplastic cells were PAS and PTAH-positive, and toluidine blue-negative. Immunohistochemistry revealed positive immunoreactivity to antibodie...