Germline Mutations Landscape in a Cohort of the State of Minas Gerais, Brazil, in Patients Who Underwent Genetic Counseling for Gynecological and Breast Cancer / Cenário de mutações germinativas em uma coorte do estado de Minas Gerais, Brasil, em pacientes submetidas ao aconselhamento genético para câncer ginecológico e de mama

Abstract Objective The present study evaluated the profile of germline mutations present in patients who underwent genetic counseling for risk assessment for breast cancer (BC), ovarian cancer (OC), and endometrial cancer (EC) with a possible hereditary pattern. Methods Medical records of 382 patients who underwent genetic counseling after signing an informed consent form were analyzed. A total of 55.76% of patients (213/382) were symptomatic (personal history of cancer), and 44.24% (169/382) were asymptomatic (absence of the disease). The variables analyzed were age, sex, place of birth, personal or family history of BC, OC, EC, as well as other types of cancer associated with hereditary syndromes. The Human Genome Variation Society (HGVS) nomenclature guidelines were used to name the variants, and their biological significance was determined by comparing 11 databases. Results We identified 53 distinct mutations: 29 pathogenic variants, 13 variants of undetermined significance (VUS), and 11 benign. The most frequent mutations were BRCA1 c.470_471delCT, BRCA1 c.4675 + 1G > T, and BRCA2 c.2T> G. Furthermore, 21 variants appear to have been described for the first time in Brazil. In addition to BRCA1/2 mutations, variants in other genes related to hereditary syndromes that predispose to gynecological cancers were found. Conclusion This study allowed a deeper understanding of the main mutations identified in families in the state of Minas Gerais and demonstrates the need to assess the family history of non-gynecological cancer for risk assessment of BC, OC, and EC. Moreover, it is an effort that contributes to population studies to evaluate the cancer risk mutation profile in Brazil.

Resumo Objetivo O presente estudo avaliou o perfil de mutações germinativas presentes em pacientes submetidas a aconselhamento genético para avaliação de risco para câncer de mama (CM), câncer de ovário (OC) e câncer de endométrio (CE) com possível padrão hereditário. Métodos Foram analisados os prontuários de 382 pacientes que realizaram aconselhamento genético após consentimento informado. Um total de 55,76% dos pacientes (213/382) eram sintomáticos (história pessoal de câncer), e 44,24% (169/382) eram assintomáticos (ausência da doença). As variáveis analisadas foram idade, sexo, naturalidade, história pessoal ou familiar de CM, OC, CE bem como outros tipos de câncer associados a síndromes hereditárias. As diretrizes de nomenclatura da Human Genome Variation Society (HGVS) foram usadas para nomear as variantes e seu significado biológico foi determinado pela comparação de 11 bancos de dados. Resultados Identificamos 53 mutações distintas: 29 variantes patogênicas, 13 variantes de significado indeterminado e 11 benignas. As mutações mais frequentes foram BRCA1 c.470_471delCT, BRCA1 c.4675 + 1G > T e BRCA2 c.2T > G. Além disso, 21 variantes parecem ter sido descritas pela primeira vez no Brasil. Além das mutações BRCA1/2, foram encontradas variantes em outros genes relacionados a síndromes hereditárias que predispõem a cânceres ginecológicos. Conclusão Este estudo permitiu conhecer melhor as principais mutações identificadas nas famílias do estado de Minas Gerais e demonstra a necessidade de avaliar a história familiar de câncer não ginecológico para avaliação do risco de CM, OC e CE. Além disso, é um esforço que contribui com estudos populacionais para avaliar o perfil de mutações de risco para câncer no Brasil.

A vivência da guarda compartilhada após o divórcio e/ou dissolução conjugal / The experience of joint custody after divorce and/or marital dissolution

O objetivo desta revisão integrativa foi investigar, em estudos acadêmicos publicados entre 2010 e 2020, como pais e filhos vivenciam a guarda compartilhada após o processo de divórcio e/ou dissolução conjugal. As bases utilizadas foram: LILACS, SciELO, MEDLINE e PsycINFO. Os descritores elencados foram: Guarda Compartilhada, Cuidados Parentais, Custódia da Criança, Divórcio, Educação Infantil, Família, Parentalidade, Poder Familiar, Relações Familiares, Relações Pais-Filho. Após a realização das buscas (N= 381), procedeu-se com a exclusão de estudos por repetição (N=121), título (N=83) e resumo (N=18). Os artigos remanescentes foram lidos na íntegra e (N=16) foram recuperados e compõem esta revisão. Os estudos apontam a dificuldade de difusão da modalidade de guarda compartilhada no Brasil, destacando fatores favoráveis e contrários à sua aplicação. Evidencia-se a necessidade de mais estudos empíricos na área, a fim de consolidar inferências consonantes em grande parte dos estudos que se mostraram relevantes na composição deste trabalho de revisão.

The objective of this integrative review was to explore how parentes and children experience joint custody after divorce and/or marital dissolution, in studies from 2015 to 2020. The data bases LILACS, SciELO, MEDLINE and PsycINFO were used. The descriptors listed were Joint Custody, Child Custody, Divorce, Child Rearing, Family, Parenting, Family Relations, Parent-Child Relations. After performing the searches (n=381), we proceeded to the exclusion of repetitive studies (n=121), title (n=83) and summary (n=18). The remaining articles were read in full and 16 were retrieved and make up this review. Studies explore the difficulty of diffusion of the modality in Brasil and shows factors considered as favorable and adversary to its application. We emphasize the importance of more studies in the area, with the aim of consolidating consonant inferences in most of the studies that proved to be relevant in the composition of this integrative review.

Interaction of Biomphalaria cells in primary cultures with Schistosoma mansoni sporocysts

Abstract INTRODUCTION: Biomphalaria snails may display varying levels of susceptibility to Schistosoma mansoni infection. We have been developing an in vitro model to study the interaction between the snail and the parasite, using tissue-derived cell cultures from Biomphalaria. METHODS: The digestive gland- and kidney-derived cells from primary cultures of resistant (B. tenagophila Taim) and susceptible (B. tenagophila HM and B. glabrata BH) strains of Biomphalaria were exposed to S. mansoni sporocysts. RESULTS: S. mansoni sporocysts were surrounded and encapsulated exclusively by cells derived from the digestive gland (DG) of B. tenagophila Taim. The process was followed by a marked decrease in the number of free sporocysts in the culture medium. The morphological characteristics of DG-derived cells in culture have been described. CONCLUSIONS: Cells derived from DG (but not SK) primary cultures of B. tenagophila Taim may participate in S. mansoni sporocyst control.

Deep sequencing of small RNAs reveals the repertoire of miRNAs and piRNAs in Biomphalaria glabrata

BACKGROUND Biomphalaria glabrata snails are widely distributed in schistosomiasis endemic areas like America and Caribe, displaying high susceptibility to infection by Schistosoma mansoni. After the availability of B. glabrata genome and transcriptome data, studies focusing on genetic markers and small non-coding RNAs have become more relevant. The small RNAs have been considered important through their ability to finely regulate the gene expression in several organisms, thus controlling the functions like cell growth, metabolism, and susceptibility/resistance to infection. OBJECTIVE The present study aims on identification and characterisation of the repertoire of small non-coding RNAs in B. glabrata (Bgl-small RNAs). METHODS By using small RNA sequencing, bioinformatics tools and quantitative reverse transcription polymerase chain reaction (RT-qPCR), we identified, characterised, and validated the presence of small RNAs in B. glabrata. FINDINGS 89 mature miRNAs were identified and five of them were classified as Mollusk-specific. When compared to model organisms, sequences of B. glabrata miRNAs showed a high degree of conservation. In addition, several target genes were predicted for all the mature miRNAs identified. Furthermore, piRNAs were identified in the genome of B. glabrata for the first time. The B. glabrata piRNAs showed strong conservation of uridine as first nucleotide at 5' end, besides adenine at 10th position. Our results showed that B. glabrata has diverse repertoire of circulating ncRNAs, several which might be involved in mollusk susceptibility to infection, due to their potential roles in the regulation of S. mansoni development. MAIN CONCLUSIONS Further studies are necessary in order to confirm the role of the Bgl-small RNAs in the parasite/host relationship thus opening new perspectives on interference of small RNAs in the organism development and susceptibility to infection.

Apoptosis-related gene expression can predict the response of ovarian cancer cell lines to treatment with recombinant human TRAIL alone or combined with cisplatin

OBJECTIVES: The objectives of this study were to determine the sensitivity of ovarian cancer (OC) cell lines (TOV-21G and SKOV-3) to cisplatin and to the recombinant human TRAIL (rhTRAIL), and to evaluate the expression profile of TNFRSF10B, TNFRSF10C, TP53TG5, MDM2, BAX, BCL-2 and CASPASE-8 genes and their participation in the resistance/susceptibility mechanism of these tumor cell lines. METHODS: To determine the IC50 values associated with Cisplatin and rhTRAIL, inhibition of cell growth was observed using MTT assays in two human OC cell lines (SKOV-3 and TOV-21G). The analysis of gene expression was performed using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Both cell lines had different susceptibility profiles to the tested drugs. In the SKOV-3 cell line, the IC50 values for cisplatin and for rhTRAIL were 270.83 ug/mL and 196.5 ng/mL, respectively. The same concentrations were used for TOV-21G. Different gene expression profiles were observed in each tested cell line. CASPASE-8 and TNFRSF10B expression levels could predict the response of both the cell lines to rhTRAIL alone or the response to a combination of rhTRAIL and cisplatin. In addition, we observed a relationship between BCL-2 and BAX expression that may be helpful in estimating the proliferation rate of the OC cell lines. CONCLUSION: SKOV-3 and TOV-21G respond differently to cisplatin and rhTRAIL exposure, and expression of CASPASE-8 and TNFRSF10B are good predictors of responses to these treatments.

Gene expression profile of ABC transporters and cytotoxic effect of ibuprofen and acetaminophen in an epithelial ovarian cancer cell line in vitro / Perfil da expressão gênica dos transportadores ABC e efeito citotóxico do ibuprofeno e acetaminofen em uma linhagem celular de câncer epitelial de ovário in vitro

PURPOSES: To determine the basic expression of ABC transporters in an epithelial ovarian cancer cell line, and to investigate whether low concentrations of acetaminophen and ibuprofen inhibited the growth of this cell line in vitro. METHODS: TOV-21 G cells were exposed to different concentrations of acetaminophen (1.5 to 15 μg/mL) and ibuprofen (2.0 to 20 μg/mL) for 24 to 48 hours. The cellular growth was assessed using a cell viability assay. Cellular morphology was determined by fluorescence microscopy. The gene expression profile of ABC transporters was determined by assessing a panel including 42 genes of the ABC transporter superfamily. RESULTS: We observed a significant decrease in TOV-21 G cell growth after exposure to 15 μg/mL of acetaminophen for 24 (p=0.02) and 48 hours (p=0.01), or to 20 μg/mL of ibuprofen for 48 hours (p=0.04). Assessing the morphology of TOV-21 G cells did not reveal evidence of extensive apoptosis. TOV-21 G cells had a reduced expression of the genes ABCA1, ABCC3, ABCC4, ABCD3, ABCD4 and ABCE1 within the ABC transporter superfamily. CONCLUSIONS: This study provides in vitro evidence of inhibitory effects of growth in therapeutic concentrations of acetaminophen and ibuprofen on TOV-21 G cells. Additionally, TOV-21 G cells presented a reduced expression of the ABCA1, ABCC3, ABCC4, ABCD3, ABCD4 and ABCE1 transporters. .

OBJETIVOS: Determinar a expressão básica dos transportadores ABC em uma linhagem celular do câncer epitelial de ovário, e investigar se o acetaminofen e o ibuprofeno em baixas concentrações são capazes de inibir o crescimento desta linhagem celular in vitro. MÉTODOS: A linhagem celular TOV-21 G foi exposta a diferentes concentrações de acetaminofen (1,5 a 15 µg/mL) e ibuprofeno (2,0 a 20 µg/mL), de 24 a 48 horas. O crescimento celular foi avaliado utilizando-se um ensaio de viabilidade celular. A morfologia celular foi determinada por meio da microscopia de fluorescência. O perfil de expressão gênica foi estabelecido por um painel de 42 genes da superfamília de transportadores ABC. RESULTADOS: Observou-se um decréscimo significativo no crescimento das células TOV-21 G expostas a 15 µg/mL de acetaminofen durante 24 (p=0,02) e 48 horas (p=0,01), ou a 20 µg/mL de ibuprofeno por 48 horas (p=0,04). Ao avaliar a morfologia das células cultivadas, não foi observada evidência de apoptose extensiva. A linhagem de células estudada subexpressa os genes de ABCA1, ABCC3, ABCC4, ABCD3, ABCD4 e ABCE1 na superfamília de transportadores ABC. CONCLUSÕES: Este estudo fornece evidências in vitro referentes aos efeitos inibidores do crescimento de concentrações terapêuticas do acetaminofen e ibuprofeno na linhagem celular testada. Além disso, as células TOV-21 G apresentaram uma expressão reduzida de genes dos transportadores ABCA1, ABCC3, ABCC4, ABCD3, ABCD4 e ABCE1. .

Histopathological and immunohistochemical aspects of American cutaneous leishmaniasis before and after different treatments* / Aspectos histopatológicos e imuno-histoquímicos da leishmaniose tegumentar americana antes e depois de diferentes tratamentos

The histopathology and immune responses of the healing process of leishmaniasis are still poorly studied. This study aimed to examine the histopathological and immunological aspects of lesions of patients with cutaneous leishmaniasis before and after different therapeutic methods. We studied 23 individuals grouped according to the treatments: Glucantime, Glucantime + Leishvacin and Glucantime + Leishvacin associated with Bacillus Calmette-Guerin. For analysis of the histopathological changes present in the dermis and epidermis, histological sections were stained with hematoxylin and eosin. The samples were immunostained before and after treatment to analyze the expression of interferon (IFN)-γ, interleukin (IL) 12, IL-10 and IL-4. Before treatment the presence of intense infiltrates of mononuclear cells was noticed and after treatment, even with a diagnosis of clinical cure, the subjects still showed a moderate inflammatory process. In the immunohistochemical analyses, we noticed a difference between the cytokines, with increased expression of cytokines IFN-γ and IL-12 compared to IL 10 and IL-4, both before and after treatment and, comparatively, the difference in this expression was more intense before treatment. However, the cytokine expression analyzed by treatment group showed no statistically significant difference. We conclude that a clinical cure does not always coincide with the histopathological ...

A histopatologia e as respostas imunológicas do processo de cura da leishmaniose são ainda pouco estudadas. Este estudo teve como objetivo avaliar os aspectos histopatológicos e imunológicos das lesões de pacientes com leishmaniose tegumentar, antes e após diferentes métodos terapêuticos. Foram estudados 23 indivíduos agrupados de acordo com os tratamentos: Glucantime, Glucantime + Leishvacin e Glucantime + Leishvacin associado com Bacilo Calmette-Guerin. Para a análise das alterações histopatológicas presentes na derme e epiderme, cortes histológicos foram corados com hematoxilina e eosina. Para avaliar a expressão de interferon (IFN)-γ, interleucina (IL) 12, IL-10 e IL-4 foi utilizada a técnica de imuno-histoquímica antes e após o tratamento. Antes do tratamento houve um intenso infiltrado de células mononucleares, após o tratamento, mesmo com um diagnóstico de cura clínica, apresentou-se ainda um moderado processo inflamatório. Na análise imuno-histoquímica, notamos uma diferença entre as citocinas, com expressão aumentada de citocinas IFN-γ e IL-12 em comparação com IL-10 e IL-4 tanto antes quanto depois do tratamento, e comparativamente, a diferença nesta expressão mostrou-se mais intensa antes do tratamento. No entanto, a expressão das citocinas analisadas por grupo de tratamento não mostraram diferenças ...

Cultura ou culturas? Concepções de cultura na Educação Física sob a perspectiva de Cuche / Culture or cultures? Conceptions of culture in physical education in the perspective of Cuche

Objetivando analisar e relacionar algumas obras da área da Educação Física, de acordo com as acepções de cultura especificadas por Cuche (2002), este trabalho pretendeu assinalar sob quais perspectivas esses referenciais estão ensejados e quais são as concepções de cultura corporal presentes em cada um. Embora muitas vezes as definições não sejam evidenciadas claramente, foi possível constatar tendências de aproximação a uma ou outra concepção de cultura, sendo ora compreendida na sua forma particularista, ora na sua forma universalista. Além disso, notou ­se que essas definições não se opõem, mas se complementam, possibilitando à Educação Física compreender que ambos os sentidos contribuem para a amplia­ção do conhecimento sobre a cultura corporal.

Aiming to analyze and correlate some works in the area of Physical Education according to the meanings of culture specified by Cuche (2002), this paper intended to emphasize which perspectives these parameters are based on and what are the conceptions of body culture stipulated by each one. Although the definitions are not so clearly evident very often, it was possible to observe trends of approach to either view, being sometimes understood in a universalist conception and sometimes in a particularist conception. It was possible to consider that these definitionsare not opposed, but fit together according to each context, enabling to Physical Education comprehend that both senses contribute to the expansion of knowledge about body culture.

Con el objetivo de analizar y correlacionar algunas obras en el área de Educación Física de acuerdo a los significados de la cultura especificado por Cuche (2002), este trabajo pretende hacer hincapié en qué perspectivas de estos parámetros se basan en. Aunque las definiciones no son tan evidentes, es posible observar tendencias de aproximación a cualquiera de las vistas, a veces en una concepción universalista y a veces en una concepción particularista. Se puede considerar que estas definiciones no se oponen, pero encajan de acuerdo a cada contexto, lo que permite la Educación Física comprender que los dos sentidos contribuyen a la expansión del conocimiento sobre la cultura del cuerpo.

Faces simétricas por reflexão das hemifaces não são mais atraentes que as faces naturais / Symmetrical faces by hemiface reflections are not more attractive than the natural ones

Com a finalidade de investigar se a simetria está relacionada à atratividade facial, vinte fotos em preto e branco de faces frontais de jovens adultos (10F, 10M) foram manipuladas por um editor gráfico de maneira a gerar faces simétricas pela reflexão de suas hemifaces direita e esquerda. Sessenta e dois voluntários julgaram a atratividade das faces simétricas e naturais por meio de uma escala visual analógica em dois experimentos. Em um experimento as faces foram apresentadas com os elementos faciais externos e no outro sem eles. Em ambos experimentos as faces naturais foram geralmente julgadas mais atrativas que as simétricas. Conclui-se que a simetria facial por reflexão das hemifaces não é fator preponderante na atratividade facial.

In order to investigate whether symmetry is related to facial attractiveness, a computer graphic software generated symmetrical faces by reflecting the right and the left hemiface of twenty frontal faces (10F, 10M) of young adults from black-and-white pictures. Applying an analogical visual scale, sixty two volunteers judged the attractiveness of the symmetrical and natural faces in two experiments. In one experiment the faces were presented with external elements and in the other without them. In both experiments, the natural faces were generally judged more attractive than the symmetrical ones. In conclusion, symmetry from reflections of the hemifaces is not a preponderant factor for facial attractiveness.

The role of GADD45A in resistance to oxidative stress-mediated cell death in human colon tumor cell lines

Objective: GADD45A is a growth arrest-associated gene, directly involved in the maintenance of genomic stability. In fact, in the absence of this protein cells became sensitized to death by ultraviolet irradiation or cisplatin. However, this role with respect to cell damage triggered by Reactive Oxygen Species (ROS) is not well understood. Thus, in an attempt to evaluate its role in oxidative stress-induced apoptosis, we analyzed its expression after induction of ROS in human colon cell lines. Material and methods: Cell lines derived from human colon tumors (RKO-AS45-1 and HuTu-80) were treated with Menadione (MEN) and Hydrogen Peroxide (HP). Next, the expression of GADD45A was evaluated by semi-quantitative RT-PCR analysis. Results: The results indicated that expression of this gene was associated with resistance to apoptosis. Additionally, cells with high expression of GADD45A were resistant to treatment with oxidative stress-inducing compounds. Conclusion: In conclusion, we propose that the expression of the GADD45A gene can be used as a functional tool to predict cellular responses to antitumor treatments.

Construindo pontes: relato de experiência de uma equipe multidisciplinar em transtornos alimentares / Building bridges: a multidisciplinary team experience report on eating disorders

O objetivo desse estudo é descrever a experiência de multi e interdisciplinaridade vivenciada pela equipe de profissionais de saúde que constitui o Grupo de Assistência em Transtornos Alimentares (GRATA) do Ambulatório de Nutrologia do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto-USP. Este artigo focaliza os recursos humanos e os modos de enfrentamento de situaçães recorrentes da prática assistencial desenvolvidas no contexto ambulatorial e hospitalar. O modelo assistencial proposto pelo GRATA é descrito como exemplo de uma práxis que fixa a interdisciplinaridade como eixo norteador da construção do conhecimento e das açães em saúde, considerando as múltiplas dimensães que envolvem o processo saúde-doença. Um conhecimento vivo é produzido a partir da convergência de múltiplos olhares disciplinares que se intercruzam. São apresentados alguns extratos de experiências que ilustram a busca de açães integradas na prestação de serviços. Assistência, ensino e pesquisa são articulados para a construção da prática assistencial. Observou-se que a equipe de saúde desenvolveu, gradualmente, um comprometimento com os reais interesses e as condiçães concretas de vida da população. Conclui-se que a abordagem interdisciplinar é a que mais se aproxima da visão da complexidade que caracteriza os cuidados em saúde, numa tentativa de superação do enfoque biomédico, remediativo e fragmentado, no campo dos transtornos alimentares.

The aim of this study is to describe the multi and interdisciplinary experience of a health workers team named Eating Disorders Care Group (EDCG / GRATA in Portuguese). This group is carried out in the Nutrology Ambulatory of the University Hospital of the Medical School of Ribeirão Preto, São Paulo University, Brazil. This paper focuses on the human resources and themultiple ways of coping with the practical situations of care in both hospital and outpatient cliniccontext. The model of care proposed by GRATA is described as an example of a praxis that elects the interdisciplinary approach as a guideline for the construction of knowledge and healthintervention considering the multiple dimensions of the ill-health process. The living knowledge is constructed from the convergence of different disciplinary perspectives. Some experiences arereported in order to illustrate the comprehensive intervention in health care. Care, teaching and research development are integrated for the construction of a care practice. The health workers team has with time developed a commitment to understand the concrete life conditions and theinterest of the assisted population. It is concluded that the interdisciplinary approach is the most appropriate to tackle the complexity of eating disorders and overcome the biomedical model ofhealth care

Convalescença: a evolução histórica de um conceito em enfermagem / Convalescence: the historical evolution of a concept in nursing

Convalescença foi descrita por Florence Nightingale como um dos mais importantes períodos na vida do paciente. O presente estudo tem como objetivos compreender o que a referida autora definia por convalescença, verificar de que forma essa idéia foi transmitida e de que maneira é exercida atualmente. Foi utilizada uma pesquisa do tipo teórico-exploratória realizada através de revisão bibliográfica em livros-texto de enfermagem fundamental. Os termos home care, reabilitação e asilo, muitas vezes são usados como locais ou situações onde a convalescença acontece.