2023 UPDATE: Luso-Brazilian evidence-based guideline for the management of antidiabetic therapy in type 2 diabetes.

BACKGROUND: The management of antidiabetic therapy in people with type 2 diabetes (T2D) has evolved beyond glycemic control. In this context, Brazil and Portugal defined a joint panel of four leading diabetes societies to update the guideline published in 2020. METHODS: The panelists searched MEDLINE (via PubMed) for the best evidence from clinical studies on treating T2D and its cardiorenal complications. The panel searched for evidence on antidiabetic therapy in people with T2D without cardiorenal disease and in patients with T2D and atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or diabetic kidney disease (DKD). The degree of recommendation and the level of evidence were determined using predefined criteria. RESULTS AND CONCLUSIONS: All people with T2D need to have their cardiovascular (CV) risk status stratified and HbA1c, BMI, and eGFR assessed before defining therapy. An HbA1c target of less than 7% is adequate for most adults, and a more flexible target (up to 8%) should be considered in frail older people. Non-pharmacological approaches are recommended during all phases of treatment. In treatment naïve T2D individuals without cardiorenal complications, metformin is the agent of choice when HbA1c is 7.5% or below. When HbA1c is above 7.5% to 9%, starting with dual therapy is recommended, and triple therapy may be considered. When HbA1c is above 9%, starting with dual therapyt is recommended, and triple therapy should be considered. Antidiabetic drugs with proven CV benefit (AD1) are recommended to reduce CV events if the patient is at high or very high CV risk, and antidiabetic agents with proven efficacy in weight reduction should be considered when obesity is present. If HbA1c remains above target, intensification is recommended with triple, quadruple therapy, or even insulin-based therapy. In people with T2D and established ASCVD, AD1 agents (SGLT2 inhibitors or GLP-1 RA with proven CV benefit) are initially recommended to reduce CV outcomes, and metformin or a second AD1 may be necessary to improve glycemic control if HbA1c is above the target. In T2D with HF, SGLT2 inhibitors are recommended to reduce HF hospitalizations and mortality and to improve HbA1c. In patients with DKD, SGLT2 inhibitors in combination with metformin are recommended when eGFR is above 30 mL/min/1.73 m2. SGLT2 inhibitors can be continued until end-stage kidney disease.

In deep bioinformatic characterization of a novel fumarate hydratase variant FH c.199T > G; (p.Tyr67Asp) in hereditary leiomyomatosis and renal cell carcinoma.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare, autosomal dominant tumor predisposition syndrome characterized by variable development of multiple skin and uterus leiomyomas and aggressive forms of renal cell carcinoma (RCC). Mutations in fumarate hydratase (FH), one of the proteins in homologous recombination repair, precede the development of HLRCC with high penetrance. Considering the risk of early metastasis of RCC, FH has been included in mutation screening panels. The identification of a pathogenic FH variant guides the screening for tumors in the carriers. However, variants of uncertain significance (VUS) are frequent findings, limiting the clinical value of the mutation screening. Here, we describe the associated phenotype and an in-depth, multi-step Bioinformatic evaluation of the germline FH c.199T > G (p.Tyr67 > Asp) variant segregated in an HLRCC family. Evidence for FH c.199T > G; (p.Tyr67Asp) pathogenicity includes the variant segregation with the disease in three affected family members, its absence in populational databases, and the deep evolutionary conservation of the Tyr67 residue. At the protein level, this residue substitution causes the loss of molecular bonds and ionic interactions, affecting molecular dynamics and protein stability. Considering ACMG/AMP criteria, we propose the reclassification of the FH c.199T > G; (p.Tyr67Asp) variant to "likely pathogenic". In addition, the in-depth, in silico approach used here allowed us to understand how and why FH c.199T > G; (p.Tyr67Asp) could cause HLRCC. This could help in clinical management decisions concerning the monitoring of unaffected family members having this variant.

Do boys with MAOA_LPR*2R allele present cognitive and learning impairments? / Meninos com o alelo maoa_lpr*2r apresentam prejuízos cognitivos e de aprendizagem?

ABSTRACT. Monoamine oxidase A (MAOA) polymorphisms have been associated with antisocial disorders. Less attention has been paid to the cognitive functioning of individuals with different MAOA alleles. No study has described the cognitive phenotype associated with the less frequent, low enzyme activity allele, MAOA_LPR*2R. Objective: We describe the cognitive correlates of boys having MAOA_LPR*2R allele, ascertained in a sample of school children with normal intelligence, not referred for behavioral disorders. Methods: Participants were eight boys, attending from the second to fifth grades in state-run schools. They were identified among 712 children with typical general cognitive ability, genotyped for MAOA_LPR polymorphism. Participants were assessed with general intelligence, mathematics and spelling achievement, and verbal and visuospatial working memory tests. Neuropsychological performance was compared to published standards, using 1 SD below the mean as a cutoff value for low performance. Results: Intelligence of boys with MAOA_LPR*2R allele varied from above average (N=2) to low average in the other children. Five out of eight boys with the MAOA_LPR*2R allele had low mathematics achievement, and three presented additional difficulties with spelling. Four out of eight children had low short-term and working memory performance. Discussion: This is the first study describing cognitive correlates and school performance in boys having the MAOA_LPR*2R allele. Having this allele, and therefore, probably low MAO-A activity, does not necessarily imply low intelligence or low school performance. However, learning difficulties, particularly in math, and low working memory performance were observed in boys having this allele. This suggests a role of MAOA in learning difficulties.

RESUMO. Polimorfismos da monoaminoxidase A (MAOA) são associados a transtornos antissociais. Menos atenção tem sido dada ao funcionamento cognitivo de indivíduos com diferentes alelos de MAOA. Nenhum estudo descreveu o fenótipo cognitivo associado ao alelo menos frequente, de baixa atividade enzimática, MAOA_LPR*2R. Objetivo: Descrevemos os correlatos cognitivos de meninos com o alelo MAOA_LPR*2R, identificados em uma amostra de escolares com inteligência normal, não encaminhados por transtornos de comportamento. Métodos: Oito meninos com o alelo MAOA_LPR*2R foram identificados entre 712 crianças genotipadas, com inteligência típica, que cursavam do 2º ao 5º ano em escolas públicas. Foram avaliados: inteligência, desempenho em matemática e ortografia, memória de trabalho verbal e visuoespacial. O desempenho foi comparado a normas publicadas, utilizando-se 1 desvio padrão (DP) abaixo da média como ponto de corte para desempenho rebaixado. Resultados: A inteligência dos meninos com alelo MAOA_LPR*2R variou de acima da média (N=2) a médio-inferior nas demais crianças. Cinco dos oito meninos com alelo MAOA_LPR*2R apresentaram desempenho rebaixado em matemática e três apresentaram dificuldades adicionais em ortografia. Quatro dos oito meninos apresentaram baixo desempenho de memória de curto prazo e de trabalho. Discussão: Este é o primeiro estudo a descrever os correlatos cognitivos e o desempenho escolar em meninos com alelo MAOA_LPR*2R. Ter esse alelo não significa necessariamente baixa inteligência ou baixo desempenho escolar. No entanto, dificuldades de aprendizagem, principalmente em matemática, e desempenho rebaixado da memória de trabalho foram observados em mais da metade dos meninos com esse alelo. Isso sugere um papel do MAOA nas dificuldades de aprendizagem.

The quandary of diagnosing mathematical difficulties in a generally low performing population / O dilema de diagnosticar dificuldades de aprendizagem da matemática em uma população com desempenho geral aquém do esperado

ABSTRACT. Brazilian students' mathematical achievement was repeatedly observed to fall below average levels of mathematical attainment in international studies such as PISA. Objective: In this article, we argue that this general low level of mathematical attainment may interfere with the diagnosis of developmental dyscalculia when a psychometric criterion is used establishing an arbitrary cut-off (e.g., performance<percentile 10) may result in misleading diagnoses. Methods: Therefore, the present study evaluated the performance of 706 Brazilian school children from 3rd to 5th grades on basic arithmetic operations addition, subtraction, and multiplication. Results: In line with PISA results, children presented difficulties in all arithmetic operations investigated. Even after five years of formal schooling, less than half of 5th graders performed perfectly on simple addition, subtraction, or multiplication problems. Conclusions: As such, these data substantiate the argument that the sole use of a psychometric criterion might not be sensible to diagnose dyscalculia in the context of a generally low performing population, such as Brazilian children of our sample. When the majority of children perform poorly on the task at hand, it is hard to distinguish atypical from typical numerical development. As such, other diagnostic approaches, such as Response to Intervention, might be more suitable in such a context.

RESUMO. O desempenho em matemática dos estudantes brasileiros mostra-se consistentemente abaixo da média mundial em estudos internacionais como o PISA. Objetivo: No presente artigo, argumenta-se que um baixo desempenho geral na matemática, a exemplo dos estudantes brasileiros, pode interferir no diagnóstico de discalculia do desenvolvimento quando um critério puramente psicométrico é usado para estabelecer um ponto de corte arbitrário (por exemplo, desempenho<percentil 10), o que pode resultar em falsos diagnósticos. Métodos: Para tanto, investigou-se o desempenho de 706 estudantes brasileiros do 3º ao 5º ano escolar em operações aritméticas básicas de adição, subtração e multiplicação. Resultados: De forma consistente com os resultados do PISA, as crianças apresentaram dificuldades em todas as operações aritméticas investigadas. Mesmo após cinco anos de escolarização formal, menos da metade dos estudantes do 5º ano foi capaz de completar a tarefa envolvendo cálculos simples de adição, subtração ou multiplicação. Conclusões: Dessa forma, os resultados reforçam o argumento de que o uso exclusivo de um critério psicométrico pode não ser apropriado para o diagnóstico de discalculia no contexto de uma população com desempenho geral baixo, como no caso crianças brasileiras da presente amostra. Quando a maioria das crianças tem um desempenho aquém do esperado, torna-se difícil distinguir o desenvolvimento numérico atípico do típico. Portanto, outras abordagens diagnósticas, como Resposta à Intervenção, podem ser mais adequadas em tal contexto.

Mobile web application for use in the Extended Family Health and Primary Care Center: content and usability validation / Aplicativo móvel para utilização do Núcleo Ampliado de Saúde da Família e Atenção Básica: validação de conteúdo e de usabilidade

ABSTRACT Purpose: to validate the content and usability of the "Network NASF" application, intended for the teams of the Extended Family Health and Primary Care Center (NASF-AB). Methods: eighteen specialists, researchers, and professionals from different fields of study participated to validate the content and usability of the application, carried out in four stages: adjustment of the instrument; administration of the Suitability Assessment of Materials (SAM); validation of the content by calculating the content validity index (CVI); and usability evaluation through the System Usability Scale (SUS), in this order. Results: the participants classified the material as valid regarding both its content and usability. The index achieved in the SAM was 83.5%, as four, out of the six topics in the instrument, had values over 0.78. Hence, these four were considered excellent, while the other two were considered good. The recommendations given by the specialized judges were accepted and the usability index (5.5%) was considered relevant. Conclusion: the application developed for NASF-AB professionals was considered valid regarding its content and usability.

RESUMO Objetivo: validar por conteúdo e usabilidade o aplicativo "NASF em Rede" direcionado para as equipes dos Núcleos Ampliados de Saúde da Família e Atenção Básica (NASF-AB). Métodos: estudo metodológico, no qual participaram 18 especialistas, pesquisadores e profissionais, com diferentes áreas de formação, com vistas à validação de conteúdo e de usabilidade do APP. Realizado em quatro etapas: adaptação do instrumento; aplicação do instrumento de Avaliação de Adequação de Materiais (SAM); validação de conteúdo por meio do cálculo do Índice de Validade de Conteúdo (IVC) e avaliação da usabilidade por meio do System Usability Scale (SUS), respectivamente. Resultados: os participantes classificaram o material como válido, tanto no que concerne ao conteúdo quanto à usabilidade. Obteve-se índice de 83,5% para o instrumental SAM, pois 04 dos 06 tópicos constantes no instrumento apresentaram valores de 0,78, os quais foram considerados excelentes e dois deles foram avaliadas como bons, sendo acolhidas as recomendações dos juízes especialistas. O índice de usabilidade (5,5%) também foi considerado relevante. Conclusão: o aplicativo desenvolvido para profissionais do NASF- AB foi considerado válido quanto ao conteúdo e à usabilidade.

O ensino de enfermagem em saúde mental na percepção de estudantes / Mental health nursing teaching based on students' perception

Objetivo: Compreender a experiência de estudantes de Enfermagem no processo de ensino-aprendizagem em saúde mental. Métodos: Estudo qualitativo, realizado com oito estudantes de enfermagem de uma instituição pública. As narrativas foram coletadas através de grupo focal, gravadas e transcritas na íntegra. A análise pautou-se na técnica de análise categorial temática. Resultados: Emergiram duas categorias analíticas: Formação em saúde mental na Graduação em Enfermagem e Experiências dos estudantes no processo de ensino-aprendizagem. Conclusão: A experiência discente apontou: a necessidade de potencializar a formação em saúde mental com a criação de disciplinas que abordassem esta área de conhecimento; desenvolvimento de estratégias de integração do conteúdo deste campo específico com o de outras disciplinas; uso de metodologias ativas e inovadoras; maiores oportunidades de atuação na Rede de Atenção Psicossocial; e desenvolvimento de práticas de cuidado em enfermagem que favoreçam a superação da estigmatização da pessoa em sofrimento psíquico. (AU)

Objective: Analyzing nursing students' experience in the teaching-learning process in mental health. Methods: Study qualitative conducted with eight nursing students from a public institution. Participants' narratives were recorded in a focus group and fully transcribed. Data analysis was based on the theme/category-based content analysis technique. Results: Two analytical categories emerged, namely: Mental Health Training in Undergraduate Nursing and Students experiences in teaching-learning process. Conclusion: Students' experience pointed towards the need of improving mental health training by creating a discipline focused on addressing this knowledge field; developing strategies focused on integrating the content of this specific field with that of other disciplines; using active and innovative methodologies; enabling greater opportunities for students to act in the Psychosocial Care Network; and developing nursing care practices to help individuals in psychological distress to overcome stigmatization. (AU)

Objetivo: Entender la experiencia de los estudiantes de enfermería en el proceso de enseñanza-aprendizaje en salud mental. Métodos: Un estudio cualitativo, realizado con ocho estudiantes de enfermería de una institución pública. Las narrativas fueron recopiladas a través de grupo focal, grabadas y totalmente transcritas. El análisis se basó en la técnica de análisis por categoría y tema. Resultados: Surgieron dos categorías analíticas: Formación en Salud Mental en enfermería del pregrado y Experiencias de los estudiantes en la participación en el proceso de enseñanza-aprendizaje. Conclusión: La experiencia de los estudiantes señaló la necesidad de potenciar la formación en salud mental con la creación de disciplina que aborde esta área del conocimiento; el desarrollo de estrategias de integración del contenido de este campo específico con el de otras disciplinas; el uso de metodologías activas e innovadoras; mayores oportunidades de acción en la Red de Atención Psicosocial; y el desarrollo de prácticas de cuidado en enfermería que favorezcan la superación de la estigmatización de la persona con sufrimientos psicológicos. (AU)

The Mini-Mental Examination for Children (MMC): Evidence of validity for children with learning difficulties / Mini-exame do estado mental para crianças (mmc): evidência de validade para crianças com dificuldades de aprendizagem

ABSTRACT The Mini-Mental Examination for Children (MMC) is a widely used tool for assessing global cognitive deficits, however,is still unknown whether MMC is sensitive for investigating cognitive profiles associated with learning difficulties (LD). Objective: Here we investigate the feasibility of using the MMC for screening school-aged children with learning difficulties in spelling and math. Methods: The MMC and other neurophysiological tests were administered to a sample of 168 children, aged 7 to 12 years. The sample was subdivided into a Control group and LD group (Math Difficulties, Spelling Difficulties, Math and Spelling Difficulties). Diagnostic accuracy was assessed with ROC analysis. Convergent and divergent validity was assessed using correlation analysis. Results: Performance on the MMC was associated with nonverbal intelligence, age and school achievement. The LD group had significantly lower performance on the MMC than the Control group. Performance on the MMC discriminated LD children with a global accuracy of around 0.80. Associations between the MMC and the other neuropsychological variables were higher for finger gnosis (r=0.40) and generally higher for early elementary school grades. The MMC proved satisfactory for identifying LD children with good accuracy. Nonverbal intelligence, and perceptual/motor abilities play an important role in MMC performance. Conclusion: The MMC could be a useful instrument for screening children with LD.

RESUMO Mini-exame mental para crianças (MMC) é uma ferramenta amplamente utilizada para avaliar déficits cognitivos globais, no entanto, ainda é desconhecido se a MMC é sensível para investigar perfis cognitivos associados a dificuldades de aprendizagem. Objetivo: Aqui nós investigamos a viabilidade de usar MMC para triagem de crianças em idade escolar com dificuldades de aprendizagem em ortografia e matemática. Métodos: MMC e outros testes neuropsicológicos foram administrados em uma amostra de 168 crianças de 7 a 12 anos de idade. A amostra foi subdividida em um Grupo Controle e um grupo LD (dificuldade na matemática, na escrita, ou na escrita e na matemática). A acurácia diagnóstica foi analisada através de uma análise de curva ROC. A validade convergente e divergente foi investigada através de análises de correlações. Resultados: A performance no MMC foi associada com a inteligência não verbal, idade e desempenho escolar. O grupo LD apresentou desempenho significativamente inferior ao Grupo Controle no MMC. A performance no MMC pôde identificar crianças LD com uma acurácia global em torno de 0.80. As associações entre MMC e outras variáveis neuropsicológicas foram maiores para gnosias digitais (r=0.40) e em geral, mais altas nas séries iniciais. O MMC se mostrou satisfatório para identificar crianças LD com uma boa acurácia. A inteligência não verbal, habilidades perceptivas/motoras tem um importante papel na performance no MMC. Conclusão: O MMC pode ser um instrumento útil para o rastreamento de crianças com LD.

Combining multi-OMICs information to identify key-regulator genes for pleiotropic effect on fertility and production traits in beef cattle.

The identification of biological processes related to the regulation of complex traits is a difficult task. Commonly, complex traits are regulated through a multitude of genes contributing each to a small part of the total genetic variance. Additionally, some loci can simultaneously regulate several complex traits, a phenomenon defined as pleiotropy. The lack of understanding on the biological processes responsible for the regulation of these traits results in the decrease of selection efficiency and the selection of undesirable hitchhiking effects. The identification of pleiotropic key-regulator genes can assist in developing important tools for investigating biological processes underlying complex traits. A multi-breed and multi-OMICs approach was applied to study the pleiotropic effects of key-regulator genes using three independent beef cattle populations evaluated for fertility traits. A pleiotropic map for 32 traits related to growth, feed efficiency, carcass and meat quality, and reproduction was used to identify genes shared among the different populations and breeds in pleiotropic regions. Furthermore, data-mining analyses were performed using the Cattle QTL database (CattleQTLdb) to identify the QTL category annotated in the regions around the genes shared among breeds. This approach allowed the identification of a main gene network (composed of 38 genes) shared among breeds. This gene network was significantly associated with thyroid activity, among other biological processes, and displayed a high regulatory potential. In addition, it was possible to identify genes with pleiotropic effects related to crucial biological processes that regulate economically relevant traits associated with fertility, production and health, such as MYC, PPARG, GSK3B, TG and IYD genes. These genes will be further investigated to better understand the biological processes involved in the expression of complex traits and assist in the identification of functional variants associated with undesirable phenotypes, such as decreased fertility, poor feed efficiency and negative energetic balance.

"Minha filha devolveu minha vida": uma cartografia da Rede Cegonha / "Mi hija me devolvió la vida": una cartografía de la Red Cigüeña / "My child gave me my life back": cartography of the "Rede Cegonha"

O estudo analisou o protagonismo do cuidado nas redes de saúde junto dos trabalhadores em uma capital do nordeste brasileiro, por meio dos entrelaces da Rede Cegonha, da Rede de Atenção Psicossocial e das Redes Vivas. Trata-se de uma pesquisa qualitativa e cartográfica sobre a experiência de uma gestante que utilizava drogas, abrangendo a participação de trabalhadores de saúde do território estudado, envolvidos no processo de cuidado. Os instrumentos e as técnicas de análises utilizados neste trabalho foram: oficinas, entrevista em profundidade, diário de campo, observação e fluxograma analisador. Dos resultados alcançados emergiram a fragilidade das redes formais para o cuidado integral dos seus usuários e a potência das redes vivas como espaços eficientes de cuidado. O estudo apresenta uma nova perspectiva de pensar as redes, os seus acessos e os seus fluxos.(AU)

El estudio analizó el protagonismo del cuidado en las redes de salud con los trabajadores en una capital del nordeste brasileño, por medio de dos entrelazamientos de la Red Cigüeña, de la Red de Atención Psicosocial y de las Redes Vivas. Se trata de una encuesta cualitativa y cartográfica sobre la experiencia de una embarazada que utilizaba drogas, incluyendo la participación de trabajadores de salud del territorio estudiado, envueltos en el proceso de cuidado. Los instrumentos y técnicas de análisis utilizados en este trabajo fueron: talleres, entrevista en profundidad, diario de campo, observación y diagrama de flujo analizados. Entre los resultados alcanzados, surgieron la fragilidad de las redes formales para el cuidado integral de sus usuarios y la potencia de las redes vivas como espacios eficientes de cuidado. El estudio presenta una nueva perspectiva para pensar las redes, sus accesos y sus flujos.(AU)

The present study analyzed the protagonist role of health workers in healthcare systems in a capital city of Northeastern Brazil, through the coordinated work of the Rede Cegonha ("Stork Network"), Psychosocial Care Networks, and Redes Vivas ("Living Networks"). This was a qualitative and cartographic study about the experience of a pregnant woman who used drugs, and the participation of health workers in the studied territory, who were involved in her care process. Data collection and analysis was carried out using workshops, in-depth interviews, field diary, observation, and flow charts. The results showed the frailty of formal networks in providing comprehensive care to its users and the power of living networks as efficient spaces of care. The study presents a new perspective for thinking networks, and their access points and work flow.(AU)

Three-Dimensional Cellular Arrangement in Epithelial Ovarian Cancer Cell Lines TOV-21G and SKOV-3 is Associated with Apoptosis-Related miRNA Expression Modulation.

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, and the lack of chemoresistance biomarkers contributes to the poor prognosis. Cancer stem cells (CSC) have been investigated in EOC to understand its relationship with chemoresistance and recurrence. In this context, in vitro cultivation-models are important tools for CSC studies. MicroRNAs (miRNAs) play key roles in cancer, CSC regulation and apoptosis. Thus, this study aims to evaluate the tumorsphere model as CSC-enrichment method in EOC studies and investigate apoptosis-related miRNAs in tumorspheres-derived EOC cell lines. TOV-21G and SKOV-3 were cultured in monolayer and tumorspheres. Genetic profiles of cell lines were obtained using COSMIC database. CD24/CD44/CD146/CD177 and ALDH1 markers were evaluated in cell lines and tumorspheres-derived by flow cytometry. Eleven miRNAs were selected by in silico analysis for qPCR analysis. According to COSMIC, TOV-21G and SKOV-3 have eight and nine cancer-related mutations, respectively. TOV-21G showed a CD44+/high/CD24-/low/CD117-/low/CD146-/low/ALDH1low profile in both culture models; thus, no significant difference between cultivation models was identified. SKOV-3 showed a CD44+/high/CD24+/high/ CD117-/low/CD146-/low/ALDH1low profile in both culture models, although the tumorsphere model showed a significant increase in CD24+/high subpopulation (ovarian CSC-like). Among eleven miRNAs, we observed differences in miRNA expression between culture models. MiR-26a was overexpressed in TOV-21G tumorspheres, albeit downregulated in SKOV-3 tumorspheres. MiR-125b-5p, miR-17-5p and miR-221 was downregulated in tumorsphere model in both cell lines. Given that tumorsphere-derived SKOV-3 had a higher ratio of CD24+/high cells, we suggest that miR-26a, miR-125b-5p, miR-17-5p and miR-221 downregulation could be related to poor EOC prognosis.

Genetic and environmental risk factors for developmental dyslexia in children: systematic review of the last decade.

Despite advances in the characterization of developmental dyslexia (DD), several questions regarding the interplay between DD-susceptibility genes and environmental risk factors remain open. This systematic review aimed at answering the following questions: What has been the impact of new resources on the knowledge about DD? Which questions remain open? What is the investigative agenda for the short term? Forty-six studies were analyzed. Despite the growing literature on DD candidate genes, most studies have not been replicated. We found large effects on causative genes and smaller environmental contributions, involving maternal smoking during pregnancy, SES and the DYX1C1-1259C/G marker. Implications are discussed.

Mini-mental state exam for children (MMC) in children with hemiplegic cerebral palsy / Mini-exame do estado mental para crianças (mmc) na paralisia cerebral

ABSTRACT Cognitive impairment is frequent in cerebral palsy (CP) and there is a lack of multiprofessional screening instruments. OBJECTIVE: The aim of this study was to investigate the utility of the Mini-Mental State Examination for Children (MMC), an adapted version of the Mini-Mental State Examination, in screening for cognitive impairments in children with CP. METHODS: We assessed 397 Brazilian children, 310 with typical development and 87 with CP (hemiplegic and quadriplegic forms), aged 5-16 years. Association between the MMC and general intelligence was assessed by the Colored Progressive Matrices instrument. RESULTS: Psychometric indexes for the MMC were adequate. ROC analyses revealed effective diagnostic accuracy in all ages assessed. Cut-off values are reported. Major difficulties on the MMC were observed in children with CP, particularly individuals with the quadriplegic form. Moreover, the MMC showed moderate correlation with the intelligence test, and was reliable in discriminating, among clinical cases, those with poorer cognitive abilities. CONCLUSION: The MMC could be useful as a multiprofessional screening instrument for cognitive impairment in children with hemiplegic CP. Results of the MMC in quadriplegic CP children should be interpreted with caution. Diagnosis should be confirmed by further psychological testing.

RESUMO Comprometimentos cognitivos são frequentes na Paralisia Cerebral (PC) e existe uma falta de instrumentos multiprofissionais para uma triagem. OBJETIVO: Investigar a viabilidade do uso do mini-exame do estado mental para crianças (MMC), uma adaptação do mini-exame do estado mental, como uma triagem para comprometimento cognitivo em crianças com PC. MÉTODOS: Nós avaliamos 397 crianças brasileiras, 310 com desenvolvimento típico e 87 com PC (hemiplégica e quadriplégica), com idades entre cinco e 16 anos. A associação entre MMC e a inteligência geral foi avaliada através das Matrizes Coloridas Progressivas de Raven. RESULTADOS: Os índices psicométricos para o MMC foram adequados. As análises ROC revelaram eficácia diagnóstica para todas as idades avaliadas. Os valores de corte são relatados. Dificuldades importantes na MMC foram observadas em crianças com PC, principalmente em crianças tetraplégicas. Além disso, MMC mostrou correlação moderada com o teste de inteligência e boa precisão na identificação das crianças com PC que possuem habilidades cognitivas prejudicadas. CONCLUSÃO: O MMC poderia ser útil como um instrumento de triagem multiprofissional para comprometimento cognitivo em crianças hemiplégicas. Os resultados de MMC em crianças tetraplégicas devem ser interpretados cuidadosamente. O diagnóstico deve ser confirmado por mais testes psicológicos.

Investigação dos domínios cognitivos de pacientes com síndrome de williams usando as escalas wechsler / Investigation of cognitive domains in williams syndrome's patients using wechsler's scales

A Síndrome de Williams (SW) é uma doença de etiologia genética, causada por microdeleções na região do cromossomo 7q11.23. Pacientes com SW podem apresentar QI verbal significativamente superior ao executivo, o que explicaria o déficit recorrente nas habilidades visoespaciais e a preservação de aspectos das habilidades verbais. O estudo teve como objetivo analisar o perfil cognitivo de uma série de casos de pacientes com SW, utilizando a Escala Wechsler de Inteligência. A amostra foi composta por dez pacientes. Os resultados apontam para um padrão de desempenho semelhante entre os participantes na escala verbal, porém o QI de execução teve maior correlação com o QI total. Foi observada uma discrepância entre habilidades verbais e não verbais em 40% dos participantes.

Williams Syndrome (WS) is a disease of genetic etiology caused by micro-deletions at the 7q11.23 region. WS's patients may present verbal IQ significantly higher than the performance one, which could explain the recurrent deficit in visuospatial abilities and the preservation of some verbal skills. The study aimed at analyzing the cognitive profile of a case series including WS patients, using Wechsler's Intelligence Scale. The sample was composed of ten patients. The results showed a similar pattern of performance among participants in the verbal scale; however, the performance IQ was more associated with total IQ. We observed a discrepancy between verbal and nonverbal abilities in 40% of the participants.

Evaluation of whole-body retention of iodine-131 ((131)I) after postoperative remnant ablation for differentiated thyroid carcinoma - thyroxine withdrawal versus rhTSH administration: A retrospective comparison.

Previous studies demonstrated that preparation with recombinant human thyroid-stimulating hormone (rhTSH) for thyroid remnant ablation results in lower extrathyroidal radiation compared to hypothyroidism. The results of 50 radioiodine therapies (RITs) under rhTSH, regarding iodine half-life, were evaluated and compared with 50 RITs performed on patients with hypothyroidism following thyroxine withdrawal. The patients were treated with 3700 MBq (100 mCi) of (131)I. Forty-eight hours after RIT, patients were measured with a radiation detector at a 1-meter (m) distance for evaluation of the effective dose (µSv/h). TSH and thyroglobulin (Tg) maximal values were also compared. rhTSH-stimulated patients had a significantly lower whole-body retention of (131)I (8.5±7.3 µSv/h), extrapolated from the measurements of the effective dose at a 1-m distance, compared to endogenously stimulated patients (13.6±8.1 µSv/h; p=0.001). Furthermore, TSH mean and Tg median levels were significantly higher in the rhTSH-stimulated patients (89.9±15.3 mU/l and 7.7 ng/ml, respectively) compared to the hypothyroid group (59.2±25.1 mU/l and 3.3 ng/ml; p<0.001 and p=0.003, respectively). Compared to thyroid hormone withdrawal, the use of rhTSH prior to RIT was associated with significantly lower whole-body retention of (131)I and with greater efficacy in reaching TSH levels greater than 30 mU/l, confirming data previously described.

The ACTN3 genotype in soccer players in response to acute eccentric training.

Genetic factors can interfere with sporting performance. The identification of genetic predisposition of soccer players brings important information to trainers and coaches for individual training loads adjustment. Different responses to eccentric training could be observed by the genotype referred to as α-actinin-3 (ACTN3) in biomarkers of muscle damage, hormones and inflammatory responses. The aim of this study was to compare acute inflammatory responses, muscle damage and hormonal variations according to the eccentric training in soccer professional athletes with different genetic profiles of ACTN3 (XX, RX and RR). 37 soccer professional athletes (9 XX, 13 RX, 15 RR) were randomly divided into five stations associated to eccentric muscle contraction and plyometrics. Blood samples were taken from athletes pre-eccentric training, immediately after (post), 2- and 4-h post-eccentric training to determine hormone responses (cortisol and testosterone), muscle damage (CK and α-actin), and inflammatory responses (IL-6). After eccentric training, athletes XX presented higher levels for CK (4-h post), α-actin (post and 2-h post) and cortisol (post) compared to RR and RX athletes. However, RR and RX athletes presented higher levels of testosterone (post) and IL-6 (2 h post and 4 h post) compared to athletes XX. The main conclusion of this study is that professional soccer athletes homozygous to ACTN3XX gene are more susceptible to eccentric damage and present a higher catabolic state, demonstrated by metabolic, hormonal and immune responses post an eccentric training, in comparison to ACTN3RR and ACTN3RX groups.

Alpha blockade with doxazosin in pheochromocytoma--report of three cases.

Pheochromocytoma is a catecholamine-secreting tumor, for which the treatment of choice is complete surgical resection, when possible. Some form of preoperative pharmacological preparation is indicated. Most centers use alpha blockade, phenoxybenzamine being the preferred drug. There is little experience with the use of other alpha-blocking agents. The authors report three different cases in which doxazosin was used: as preoperative preparation of a patient with pheochromocytoma, as preparation for therapy in I-131-MIBG of a patient with a malignant pheochromocytoma, and as a pre-cesarean preparation in a pregnant woman with multiple endocrine neoplasia type 2A (MEN-2A). Doxazosin provided a safe alternative to phenoxybenzamine in the three cases described, with some advantages that the authors summarize.

[Malnutrition in morbid obesity]. / Desnutrição na obesidade mórbida.

Nutritional deficiences are common in patients who have undergone bariatric surgery for morbid obesity. There are limited data on nutritional status before surgery. We now begin to realize the importance and the high frequency of that situation in the morbidly obese who have never undergone any invasive procedure. It is very important to acknowlegde this fact, so that specific therapy is begun before surgery. It is our conviction that in doing so we minimize the risk of having serious deficiencies after surgery. We report a case of a morbidly obese woman with nutritional deficiencies before bariatric surgery.

Mutational analysis of two boys with the severe perinatally lethal Melnick-Needles syndrome.

Melnick-Needles syndrome (MNS) (OMIM 309350) is a rare, X-linked dominant condition, caused by mutations in the filamin A gene (FLNA, on Xq28). In females, the syndrome presents with bone dysplasia and characteristic facial changes. Affected males may show two different phenotypes. One is similar to the female phenotype and is seen in children born to unaffected mothers and suggesting new mutations. Alternatively, males born to affected mothers have an embryonic or perinatally lethal disorder. It has been claimed that MNS constitutes part of a spectrum including frontometaphyseal dysplasia, otopalatodigital syndrome type 1 (OPD1) and otopalatodigital syndrome type 2 (OPD2). These conditions are produced by different mutations in the filamin A gene (FLNA). MNS is caused by three different mutations in FLNA exon 22, to date detected only in females. We describe the clinical manifestations and present the results of FLNA exon 22 mutations screening in two boys with the perinatally lethal form of MNS and their affected mothers. In order to obtain DNA amplification from paraffin-embedded tissues, we designed a new method based on hemi-nested PCR. One of the children (and his mother) had a previously undescribed mutation produced by a double SNP in the positions 3776 and 3777 of the gene and leading to an amino acid substitution (NP_001447:p.[Gly1176Asp]). The second child (and his mother) had an already known mutation (NP_001447.2:p[.Ser1199Leu]). This is the first report confirming the presence FLNA mutations in boys with the perinatally lethal phenotype of MNS. (

Diel feeding pattern and diet of rough scad Trachurus lathami Nichols, 1920 (Carangidae) from the Southwestern Atlantic

Diel changes in feeding activity and dietary composition of the rough scad Trachurus lathami were investigated through the analysis of stomach contents of 307 fish sampled over a 24-h period on the continental shelf off Ubatuba (23º 35'S 45ºW). Stomach contents were analyzed by frequency of occurrence (O percent), percent number (N percent), percent mass (M percent), and feeding index (FI percent = O percent * M percent). Rough scad fed on mollusks (Gastropoda, Crepidula sp.), crustacean (Ostracoda, Copepoda, decapod larvae), chaetognat and teleostean fish. The main items were calanoid copepods (Eucalanus sp. and Centropages sp.). According to the analysis of the stomach fullness and prey digestion, T. lathami is both a diurnal and nocturnal feeder, showing some seasonal variation in feeding time. According to the Chronobiology concept, it was raised the hypothesis of circadian rhythm in feeding of this fish, probably synchronized by light/dark cycle.

O estudo da dieta e do padrão diário e sazonal de atividade alimentar do chicharro Trachurus lathami foi realizado através de análises dos conteúdos estomacais de 307 peixes amostrados em estações fixas de coleta de 24 horas na plataforma continental ao largo de Ubatuba (23º 35'S 45ºW). Os conteúdos estomacais foram analisados através da freqüência numérica (N por cento), massa porcentual (M por cento) e freqüência de ocorrência (O por cento) dos itens alimentares, e índice alimentar (O por cento * M por cento). A espécie caracterizou-se por ingerir principalmente copépodes calanóides (ex. Eucalanus sp. e Centropages sp.), além de outros crustáceos (Ostracoda, larva de decápodes), moluscos (Gastropoda: Crepidula sp.), quetognatos e peixes teleósteos. De acordo com o grau de repleção estomacal e grau de digestão das presas, T. lathami ingeriu alimento tanto na fase clara quanto na fase escura do dia, apresentando variação sazonal no horário de tomada de alimento. De acordo com os conceitos da Cronobiologia foi levantada a hipótese de ritmo circadiano na atividade alimentar, provavelmente sincronizado pelo ciclo claro/escuro.

Validação da bateria de avaliação da memória de trabalho (BAMT-UFMG) / Validation of a battery for working memory assessment (BAMT-UFMG)

A memória de trabalho pode ser concebida em termos de sistemas de armazenamento ou por meio de modelos processuais ou dinâmicos. Nós adaptamos, para uso com a população brasileira, uma bateria de testes baseada em um modelo que divide a memória de trabalho em três aspectos: eficiência ou velocidade de processamento, armazenamento temporário e coordenação de operações. O exame das características psicométricas do instrumento, aplicado em 832 participantes de diversas faixas etárias e níveis educacionais, revelou sua adequação para uso em nosso meio, preservando as características do procedimento original e mostrando coeficientes aceitáveis de fidedignidade e de validade. O desempenho nos testes se correlacionou com o desempenho em testes de função executiva e de inteligência fluida, mas não se correlacionou com testes de memória associativa episódica. O programa de pesquisa deve continuar com o exame da utilidade clínica da BAMT-UFMG em neuropsicologia