Pathological Character of Modifications to Coincident General Relativity: Cosmological Strong Coupling and Ghosts in f(Q) Theories.

The intrinsic presence of ghosts in the symmetric teleparallel framework is elucidated. We illustrate our general arguments in f(Q) theories by studying perturbations in the three inequivalent spatially flat cosmologies. Two of these branches exhibit reduced linear spectra, signalling they are infinitely strongly coupled. For the remaining branch we unveil the presence of seven gravitational degrees of freedom and show that at least one of them is a ghost. Our results rule out f(Q) cosmologies and clarify the number of propagating degrees of freedom in these theories.

Tendências internacionais da Educação Física Argentina: a reinvenção de uma tradição / International trends of Argentine Physical Education: the reinvention of a tradition / Tendencias internacionales de la Educación Física Argentina: la reinvención de una tradición

RESUMO Descreve-se a presença de teorias internacionais na Educação Física argentina a partir dos anos 1970. Demonstra-se como o diálogo com autores e literatura do exterior, particularmente Alemanha, França, Espanha, Portugal e Brasil, foi importante para a crítica à tradição da disciplina, o que permitiu uma renovação do seu estatuto epistemológico e pedagógico, com reflexos na legislação curricular atual. Utiliza-se, como fonte, de entrevistas com quatro docentes universitários argentinos e bibliografia disponível a respeito do tema.

ABSTRACT It describes the presence of international theories in Argentine Physical Education since the 1970s. It demonstrates how the dialogue with authors and literature from abroad, particularly Germany, France, Spain, Portugal and Brazil, was important for the criticism of the tradition of the discipline, which allowed a renewal of its status epistemological and pedagogical, with reflections on the current curricular legislation. It uses, as a source, interviews with 4 Argentine university professors and the available bibliography on the subject.

RESUMEN Describe la presencia de teorías internacionales en la Educación Física Argentina desde la década de 1970. Demuestra cómo el diálogo con autores y literatura del extranjero, particularmente Alemania, Francia, España, Portugal y Brasil, fue importante para la crítica de la tradición de la disciplina, que permitió una renovación de su estatus. epistemológico y pedagógico, con reflexiones sobre la legislación curricular vigente. Utiliza, como fuente, entrevistas con 4 profesores universitarios argentinos y la bibliografía disponible sobre el tema.

Vitamin D receptor hypermethylation as a biomarker for pediatric adrenocortical tumors.

Objective: Pediatric adrenocortical tumors (pACT) display complex genomic backgrounds, lacking robust prognostic markers and targeted therapeutic options. Vitamin D3 receptor (VDR) promoter hypermethylation and underexpression were reported in adrenocortical carcinomas from adult patients. In this study, we aimed to investigate VDR expression levels and methylation status in pACT and their clinical and prognostic significance. Design: Retrospective cross-sectional study enrolling pediatric patients with ACT from two tertiary referral institutions. Methods: We evaluated clinicopathological features, VDR mRNA (qPCR) and protein (immunohistochemistry) expression, and VDR-wide methylation of ACT samples from 108 pediatric patients. Fourteen pediatric and 32 fetal and postnatal normal adrenals were used as controls. Results: Unlike in pre- and post-natal normal adrenals, most pACT lacked nuclear VDR expression and had reduced mRNA levels, especially the carcinomas. Unsupervised analysis of VDR methylation data revealed two groups of pACT with distinct disease features and outcomes. Tumors with high VDR methylation presented lower mRNA levels, and the respective patients presented advanced disease and reduced disease-free and overall survival. Conclusions: VDR has a role in normal adrenocortical development and homeostasis, which is impaired during tumorigenesis. VDR hypermethylation and underexpression may be both predictive and prognostic biomarkers for pACT.

Impact of drains positioning on pulmonary function after coronary artery bypass grafting: an observational study.

INTRODUCTION: Coronary artery bypass grafting (CABG) is a procedure associated with a decline in pulmonary function. Among the main causes is the presence of the drain that is usually positioned in the intercostal or subxiphoid region. OBJECTIVE: To measure the interference of drains positioning on pulmonary function in patients undergoing CABG. METHODS: Observational study that assessed preoperative pulmonary function through vital capacity (VC), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and peak expiratory flow (PEF). These variables were evaluated in three different moments: in the presence of two drains, when removing one, and after removing all drains. RESULTS: We evaluated 45 patients with a mean age of 62 ± 7 years with male prevalence of 29 (64%) individuals. The insertion of drains caused a decline in pulmonary function after surgery by reducing MIP by 48%, MEP by 11%, VC by 39%, and PEF by 6%. CONCLUSION: This study has demonstrated that drains positioning after CABG surgery may produce weakness of the respiratory muscles, change ventilatory mechanics, and impair normal pulmonary function postoperatively.

A two-year follow-up of asfotase alfa replacement in a patient with hypophosphatasia: clinical, biochemical, and radiological evaluation.

Hypophosphatasia (HPP) is a rare disease with a high mortality rate in its severe forms. It is caused by mutations within the gene encoding the tissue-nonspecific alkaline phosphatase (TNSALP), an enzyme responsible for bone mineralization. In 2015, the Food and Drug Administration approved the use of asfotase alfa, the first medication showing benefit in the treatment of HPP. We describe a case with a 2-year follow-up of the first Brazilian child treated with asfotase alfa. A 5-year-old boy, born to consanguineous parents, was diagnosed with HPP at the age of 20 months. During prenatal ultrasonography, polyhydramnios and shortening of long bones were detected. After birth, he presented delayed motor development, repeated respiratory infections, and bone deformities. At the age of 2 years and 8 months, he started walking and had already lost his primary teeth. He had reduced levels of alkaline phosphatase (ALP), elevated levels of pyridoxal 5'-phosphate (PLP), and a p.Ala33Val (c.98C>T) missense mutation in homozygosis in the TNSALP gene. His parents and sister also had reduced ALP levels, high PLP levels, and the same mutation in heterozygosis. His father and sister were healthy, and his mother was diagnosed with rickets in childhood, which resulted in short physical stature and lower limb deformities. The patient was started on asfotase alfa at the age of 2 years and 10 months. After 2 years of treatment, he improved his motor skills, had no further episodes of severe respiratory infection, and showed improved radiological findings of rickets, without any severe side effect.

New glycemic metrics and traditional clinical and laboratory profiles of children and adolescents with type 1 diabetes mellitus in an outpatient follow-up.

INTRODUCTION: This study evaluated the demographic, clinical, and laboratory data - including traditional (as glycated hemoglobin, HbA1c) and new glycemic metrics (as time in range, TiR) - and the complications present in children and adolescents (CA) in outpatient follow-up, as well as their possible associations. METHODS: This retrospective observational study's data were compiled from the CA's medical records with T1DM (n = 78) being followed up at the Pediatric Endocrinology Service of the Federal University of Uberlândia. RESULTS: The average participants' age was 10.2 years (1-16), most of them (55%) being male, with a diagnosis time of 4.5 years (1-13), and a body mass index of 18 kg/m2. The group had HbA1c levels of 9.6% and an estimated average glycemia of 229.5 ± 103 mg/dL. TiR was 25% (7-54%); the short- (CV%) and medium-term (ΔHbA1c) glycemic variability was 45.7% and 1.5%, respectively. Approximately 10% had diabetes ketoacidosis in the last year of follow-up, about 6% had chronic complications, such as nephropathy or retinopathy, and 20% had some other associated autoimmune disease. 49% of the participants reported regular physical activity. CONCLUSION: The high values of HbA1c and glycemic variability amplitude, short TiR, and the early presence of chronic complications reveal that the treatment did not reach its goal in this population. Better education of patients and their families about the disease and greater adherence to intensive insulin treatment can optimize the control of diabetes in pediatric patients.

Quantitative study of wild animals received at the Wild Animals Triage Centers (CETAS) in Bahia and identification of trafficking routes / Estudo quantitativo de animais silvestres recebidos nos Centros de Triagens de Animais Silvestres (CETAS) da Bahia e identificação de rotas de tráfico

In Brazil, the illegal capture of wild animals is a crime that contributes to the extinction of species, besides causing environmental imbalance and suffering to the animals. Here, we undertook a quantitative survey of animals sent to the "Centro de Triagem de Animais Silvestres" (CETAS - Wild Animals Triage Centers) from units of Porto Seguro, Salvador, and Vitória da Conquista during 2009-2019. The 19,317, 34,460, and 43,874 specimens were registered in the units of Porto Seguro, Vitória da Conquista, and Salvador, respectively. The distribution of the totals by class included 80,948 (82.90%) birds, 12,007 (12.30%) reptiles, 4,661 (4.77%) mammals, and 35 arachnids (0.03%). The operations that generated registration at the CETAS were most frequently apprehensions (67,974; 69.67%), followed by voluntary surrender (13,367; 13.69%), rescues (12,803; 13.11%), and transfers (2,735; 2.67%). The animals came from 236 municipalities in the state of Bahia, with emphasis on the municipalities of Salvador, Vitória da Conquista, Feira de Santana, Lençóis, Jequié, and Paulo Afonso. The evaluation of the quantitative seizures by municipalities indicates that the BR-116 is one of the most representative routes for the illegal traffic of wild animals in the state of Bahia and the country.(AU)

No Brasil a captura ilegal de animais silvestres é crime e contribui para a extinção das espécies, além de causar desequilíbrios ambientais e sofrimentos aos animais. Este trabalho apresenta quantitativos de animais recebidos e/ou armazenados nos Centros de Triagem de Animais Silvestres (CETAS) do estado da Bahia, no período de 2009-2019. Os totais de 19.317, 34.460 e 43.874 espécimes foram registrados nas unidades de Porto Seguro, Vitória da Conquista e Salvador, respectivamente. A distribuição dos totais por classe incluiu 80.948 (82,90%) aves, 12.007 (12,30%) répteis, 4.661 (4,77%) mamíferos e 35 aracnídeos. Quanto à natureza da operação que gerou o registro nos CETAS, as mais frequentes foram apreensão (67.974; 69,67%), entrega voluntária (13.367; 13,69%), resgate (12.803; 13,11%) e transferência (2.735; 2,67%). Os animais foram apreendidos em 236 municípios do estado da Bahia, com destaque para Salvador, Vitória da Conquista, Feira de Santana, Lençóis, Jequié e Paulo Afonso. A avaliação dos quantitativos das apreensões por municípios indica que a BR-116 é uma das rotas de escoamento mais representativa do tráfico ilegal de animais silvestres, no estado da Bahia e no país.(AU)

Quantitative study of wild animals received at the Wild Animals Triage Centers (CETAS) in Bahia and identification of trafficking routes

ABSTRACT: In Brazil, the illegal capture of wild animals is a crime that contributes to the extinction of species, besides causing environmental imbalance and suffering to the animals. Here, we undertook a quantitative survey of animals sent to the Centro de Triagem de Animais Silvestres (CETAS - Wild Animals Triage Centers) from units of Porto Seguro, Salvador, and Vitória da Conquista during 2009-2019. The 19,317, 34,460, and 43,874 specimens were registered in the units of Porto Seguro, Vitória da Conquista, and Salvador, respectively. The distribution of the totals by class included 80,948 (82.90%) birds, 12,007 (12.30%) reptiles, 4,661 (4.77%) mammals, and 35 arachnids (0.03%). The operations that generated registration at the CETAS were most frequently apprehensions (67,974; 69.67%), followed by voluntary surrender (13,367; 13.69%), rescues (12,803; 13.11%), and transfers (2,735; 2.67%). The animals came from 236 municipalities in the state of Bahia, with emphasis on the municipalities of Salvador, Vitória da Conquista, Feira de Santana, Lençóis, Jequié, and Paulo Afonso. The evaluation of the quantitative seizures by municipalities indicates that the BR-116 is one of the most representative routes for the illegal traffic of wild animals in the state of Bahia and the country.

RESUMO: No Brasil a captura ilegal de animais silvestres é crime e contribui para a extinção das espécies, além de causar desequilíbrios ambientais e sofrimentos aos animais. Este trabalho apresenta quantitativos de animais recebidos e/ou armazenados nos Centros de Triagem de Animais Silvestres (CETAS) do estado da Bahia, no período de 2009-2019. Os totais de 19.317, 34.460 e 43.874 espécimes foram registrados nas unidades de Porto Seguro, Vitória da Conquista e Salvador, respectivamente. A distribuição dos totais por classe incluiu 80.948 (82,90%) aves, 12.007 (12,30%) répteis, 4.661 (4,77%) mamíferos e 35 aracnídeos. Quanto à natureza da operação que gerou o registro nos CETAS, as mais frequentes foram apreensão (67.974; 69,67%), entrega voluntária (13.367; 13,69%), resgate (12.803; 13,11%) e transferência (2.735; 2,67%). Os animais foram apreendidos em 236 municípios do estado da Bahia, com destaque para Salvador, Vitória da Conquista, Feira de Santana, Lençóis, Jequié e Paulo Afonso. A avaliação dos quantitativos das apreensões por municípios indica que a BR-116 é uma das rotas de escoamento mais representativa do tráfico ilegal de animais silvestres, no estado da Bahia e no país.

Síndrome de burnout e saúde ocupacional em educadores de uma unidade pré-escolar / Burnout syndrome and occupational health in educators in a pre-school unit

A Síndrome de Burnout é uma doença que causa graves danos à saúde mental e física das pessoas atingindo a esfera social e profissional, deixando-as impossibilitadas de exercerem suas atividades profissionais. Existem diversos estudos sobre a Síndrome de Burnout em educadores, porém poucos estudos foram publicados a respeito deste tema em 06 professores de educação infantil. Nossa pesquisa aplicou o Job Diagnostic Survey para avaliar se existem indicadores da síndrome em uma escola de educação infantil no Vale do Itajaí. Os resultados mostram um alto nível de exaustão emocional e despersonalização, indicadores da Síndrome de Burnout. Em contrapartida existe um elevado nível de realização pessoal, o que pode indicar um grau de sofrimento psíquico alto, acompanhado de uma satisfação pelo seu trabalho.(AU)

The Burnout Syndrome is a disease that causes great injury to mental and physical health of people. Reaching social and professional sphere, leaves them unable to perform their professional activities. There are several studies about Burnout Syndrome in educators, but few studies have been published on this topic in early six childhood teachers. Our research applied the Job Diagnostic Survey to assess whether there are indicators of the syndrome in a preschool in Vale do Itajaí. The results show a high level of emotional exhaustion and depersonalization, indicators of Burnout Syndrome. On the other hand, there is a high level of personal fulfillment, which may indicate a high degree of psychological distress, accompanied by a satisfaction with your work.(AU)

Antioxidant, anti-inflammatory and cytotoxic/antitumoral bioactives from the phylum Basidiomycota and their possible mechanisms of action.

Biologically active compounds from species of the phylum Basidiomycota have been shown a wide range of pharmacological activities and provide a vast reservoir of potential innovational drugs. The aim of this review is to discuss some mechanisms of action involved in antioxidant, anti-inflammatory and cytotoxic/antitumoral activities attributed to the bioactive compounds from species of the phylum Basidiomycota. We show that isolated compounds from extracts, secondary metabolites and polysaccharides that presented antioxidant properties have mechanisms of action involved in the elimination/capture of free radicals and reduction of lipid peroxidation. Also, some bioactives with anti-inflammatory activity were reported to enhance innate and cell-mediated immune responses. Finally, compounds that presented cytotoxic/antitumoral activity induces increased free radical production, collapse of the mitochondrial membrane potential and increased expression of proteins responsible for cell cycle arrest and apoptosis. Investigating the mechanisms of action of biologically active compounds will facilitate further efforts to accelerate the discovery of novel therapeutic strategies.

"Vamos nos movimentar": uma ação para mulheres de todas as idades / "Let's move": an action for women of all ages / "Movámonos": una acción para mujeres de todas las edades

O projeto "Vamos nos movimentar" tem como objetivo oportunizar espaços de fomento à prática da atividade física para mulheres de todas as idades, especialmente as idosas, por meio de experiências relacionadas à dança e à ginástica. As vivências corporais são coletivas e ao mesmo tempo realizadas individualmente, respeitando-se a especificidade de cada participante, bem como suas possibilidades e limitações, o que tem contribuído para o autoconhecimento, a autoestima, a conscientização corporal, a autonomia e a qualidade de vida necessária ao longo da vida.

The project "Let's move" aims to provide spaces of development of physical activity for women of all ages, including the long-lived, through experiences related to dance and gymnastics. The corporal experiences are collective and at the same time realized individually, respecting the specificity, as well as the possibilities and limitations of each participant, which has contributed to self-knowledge, self-esteem, bodily awareness, autonomy and the quality of life needed throughout life.

El proyecto "Let's Move" tiene como objetivo proporcionar oportunidades para la promoción de la actividad física para mujeres de todas las edades, incluidas las de larga vida, a través de experiencias relacionadas con la danza y la gimnasia. Las experiencias corporales son colectivas y al mismo tiempo se realizan individualmente, respetando la especificidad, así como las posibilidades y limitaciones de cada participante, lo que ha contribuido al autoconocimiento, la autoestima, la conciencia corporal, la autonomía y la calidad de vida necesarias para el individuo. toda mi vida.

Genetic diversity of piroplasmids species in equids from island of São Luís, northeastern Brazil.

Equine piroplasmosisis, a tick-borne disease caused by the intra-erythrocytic protozoans Babesia caballi and Theileria equi, has economic importance due to the international trade and the increased movement of horses all over the world. The goal of this study was to evaluate the occurrence of phylogenetic diversity of T. equi and B. caballi genotypes among infected equids from São Luís Island, state of Maranhão, northeastern Brazil. Between December of 2011 and June of 2012, EDTA-blood and serum samples were collected from 139 equids (90 donkeys, 39 horses and 10 mules). From 139 serum samples submitted to ELISA assay, IgG antibodies to T. equi and B. caballi were detected in 19.4% (27/139) and 25.2% (35/139), respectively. Among sampled animals, 21.6% (30/139) and 55.4% (77/139) were positive for cPCR assays for T. equi and B. caballi, based on ema-1 and rap-1 genes, respectively. Overall, the T. equi sequences (n=7) submitted to Maximum Likelihood analysis (based on a 18S rRNA fragment of 1700 bp after alignment) grouped into three main groups, which were subdivided in eight clusters. The present work showed that different genotypes of T. equi and B. caballi circulate among equids in Brazil.

Genetic diversity of piroplasmids species in equids from island of São Luís, northeastern Brazil / Diversidade genética de espécies de piroplasmídeos em equídeos na ilha de São Luís, Nordeste do Brasil

Abstract Equine piroplasmosisis, a tick-borne disease caused by the intra-erythrocytic protozoans Babesia caballi and Theileria equi, has economic importance due to the international trade and the increased movement of horses all over the world. The goal of this study was to evaluate the occurrence of phylogenetic diversity of T. equi and B. caballi genotypes among infected equids from São Luís Island, state of Maranhão, northeastern Brazil. Between December of 2011 and June of 2012, EDTA-blood and serum samples were collected from 139 equids (90 donkeys, 39 horses and 10 mules). From 139 serum samples submitted to ELISA assay, IgG antibodies to T. equi and B. caballi were detected in 19.4% (27/139) and 25.2% (35/139), respectively. Among sampled animals, 21.6% (30/139) and 55.4% (77/139) were positive for cPCR assays for T. equi and B. caballi, based on ema-1 and rap-1 genes, respectively. Overall, the T. equi sequences (n=7) submitted to Maximum Likelihood analysis (based on a 18S rRNA fragment of 1700 bp after alignment) grouped into three main groups, which were subdivided in eight clusters. The present work showed that different genotypes of T. equi and B. caballi circulate among equids in Brazil.

Resumo A piroplasmose equina, uma doença transmitida por carrapatos e causada pelos protozoários intra-eritrocíticos Babesia caballi e Theileria equi, tem importância econômica devido ao comércio internacional e ao aumento do movimento de cavalos em todo o mundo. O objetivo do presente estudo foi mostrar a diversidade filogenética de T. equi e B. caballi infectando cavalos, burros e jumentos na Ilha de São Luís, Estado do Maranhão, Nordeste do Brasil. Entre dezembro de 2011 e junho de 2012, amostras de sangue com EDTA e soro de foram coletadas de 139 equídeos (90 jumentos, 39 cavalos e 10 burros). Dentre as 139 amostras de soro submetidas ao ensaio de ELISA, foram detectados anticorpos IgG contra T. equi e B. caballi em 19,4% (27/139) e 25,2% (35/139), respectivamente. Entre os animais amostrados, 21,6% (30/139) e 55,4% (77/139) foram positivos por meio dos ensaios de cPCR para T. equi e B. caballi, com base nos genes ema-1 e rap-1, respectivamente. No geral, as sequências T. equi (n = 7) submetidas à análise de Máxima Verossimilhança (baseada em um fragmento do 18S rRNA de 1700 pb, após o alinhamento) foram agrupadas em três grupos principais, os quais foram subdivididos em oito grupos. O presente trabalho mostrou que diferentes genótipos de T. equi e B. caballi circulam entre equídeos no Brasil.

Occupational and life-style factors-acquired mutagenicity in agric-workers of northeastern Brazil.

Pesticides are a complex mixture of chemicals used to protect crops from a number of pests and diseases. They have been considered as potential mutagenic agents. This study aims at evaluation of the mutagenic effect of pesticide exposure to agricultural workers through chromosomal aberrations (CA) and micronucleus (MN) assay in peripheral blood lymphocytes and oral mucosal cells, respectively. The exposed group was consisted with 97 farmers, while the control (un-exposed) group consisted of 55. The results showed a significant (p < 0.05) increase in frequency of CA and MN in the exposed group. Both CA and MN profiles were linked to a significant (p < 0.05) co-relation with the confounding factors such as smoking habits, alcohol, vegetables, tea/coffee, vitamins, and sweetener consumptions. More cytogenetic events were denoted in smoking and alcohol consumption as well as non-personal protective equipment (non-PPE) and low/no vegetables user farmers. In conclusion, a deficiency of dietary and medicaments-derived antioxidants, while consumption of alcohol and tobacco, as well as effects of radiation, heavy metal poisoning (especially from sweeteners), and non-PPE using habits, may contribute cytogenetic damage to the workers.

Comparative morphology of the reproductive system of seven species of ostariophysan fishes from the upper Das Velhas River, Brazil.

The success of fishes in different environments is related with the variation of reproductive strategies developed by the systematic group, which is reflected in the morphology of the reproductive system and can have ecological and evolutionary implications. This study comparatively analyzed the morphological characteristics of the male and female reproductive systems of ostariophysan fish species from the upper Das Velhas River in the São Francisco River basin, Brazil. In order to accomplish this, 393 specimens belonging to seven fish species were sampled between April 2010 and June 2015 for histological, ultrastructural, histochemical, and morphometric analyses. All the species examined have anastomosing tubular testes with unrestricted distribution of spermatogonia. Astyanax bimaculatus, A. fasciatus, A. scabripinnis, and Harttia torrenticola had their spermatozoa embedded in a glycoprotein secretion within the tubule lumen. Most species had type I spermiogenesis, whereas Rhamdia quelen had type III spermiogenesis. While all females examined had asynchronous oocyte development, there were remarkable morphological, histochemical, and morphometric differences in the ovarian follicles and enveloping layers. Hoplias malabaricus and H. torrenticola, which exhibit parental care behaviour, had a significantly larger diameter of vitellogenic oocytes and larger spermatozoa nuclei. Apareiodon ibitiensis, H. torrenticola, and A. scabripinnis, species that have rheophilic preferences, exhibited a thicker zona radiata than the other species examined. The follicular cells of R. quelen and H. torrenticola were columnar and produced a jelly coat and mucosubstances, respectively. The females of the seven fish species studied show a correlation of the reproductive strategies with the reproductive system morphology, while males retained more similar morphological characteristics between species. J. Morphol. 278:170-181, 2017. © 2016 Wiley Periodicals,Inc.

Unraveling the expression of the oncogene YAP1, a Wnt/beta-catenin target, in adrenocortical tumors and its association with poor outcome in pediatric patients.

BACKGROUND: Overexpression of the oncogene yes-associated-protein-1 (YAP1) is associated with increased cell proliferation in human cancers. YAP1 is a potential target of the Wnt/beta-catenin pathway, which plays an important role in adrenocortical tumors (ACT). The role of YAP1 in adrenocortical tumorigenesis has not been assessed. AIMS: To evaluate YAP1 expression in normal adrenals and pediatric ACT and its association with disease outcome. To investigate the interaction between YAP1 and the Wnt/beta-catenin pathway in adrenocortical cells. RESULTS: Strong YAP1 staining was present in fetal adrenals and pediatric ACT but weak in postnatal adrenals. In pediatric ACT, YAP1 mRNA overexpression was associated with death, recurrent/metastatic disease and lower overall survival. The inhibition of the Wnt/beta-catenin pathway increased YAP1 mRNA expression. siYAP1 increased CTNNB1/beta-catenin expression and nuclear staining regardless of DLV2, moreover, it decreased cell growth and impaired cell migration. MATERIALS AND METHODS: We assessed in 42 pediatric ACT samples the YAP1 protein expression by immunohistochemistry and mRNA expression by RT-qPCR and analyzed their association with outcome. As controls, we resort 32 fetal and postnatal normal adrenals for IHC and 10 normal adrenal cortices for RT-qPCR. The interaction between YAP1 and the Wnt/beta-catenin pathway was assessed in NCI-H295 adrenocortical cells by inhibiting the TCF/beta-catenin complex and by knocking down YAP1. CONCLUSION: YAP1 overexpression is a marker of poor prognosis for pediatric patients with ACT. In adrenocortical cells, there is a close crosstalk between YAP1 and Wnt/beta-catenin. These data open the possibility of future molecular therapies targeting Hippo/YAP1 signaling to treat advanced ACT.

Genotoxic and Mutagenic Activity of PT-31.

Toxicity assessment is an important tool in drug discovery and development. PT-31 (3-(2-chloro-6-fluorobenzyl)-imidazolidine-2,4-dione) is an imidazolidine- 2,4-dione analogue of clonidine that displays a dose-dependent analgesic profile and synergism with morphine. This study investigated genotoxic and mutagenic effects of PT-31 in Swiss mice. For this, ten mice (M1:F1) per group were treated with PT-31 intraperitoneally (i.p.) at 0.5, 1.0 and 5.0 mg/kg. The dimethyl sulfoxide (0.5%) and 50 mg/kg cyclophosphamide (i.p.) were taken as negative (NC) and positive controls, respectively. The bone marrow cells were collected after 24 h, while peripheral blood after 30 min, 12 h and 24 h of the treatment for the comet assay. Micronucleus (MN) test was performed only on bone marrow cells collected after 24 h of i.p. treated animals. A hundred cells were considered for the comet assay and quantification of the index of damage and frequency of damage. Lack of genotoxicity with 0.5 mg/kg of PT-31 and DNA repair ability with 0.5 and 1.0 mg/kg doses at 12 h and 24 h in comparison to NC group was observed (P<0.05). There was an increase in MN formation by PT-31 1.0 and 5.0 mg/kg treated female and male mice, respectively. PT-31 induced genotoxic and mutagenic effects only in higher doses.

Inhibition of the Tcf/beta-catenin complex increases apoptosis and impairs adrenocortical tumor cell proliferation and adrenal steroidogenesis.

BACKGROUND: To date, there is no effective therapy for patients with advanced/metastatic adrenocortical cancer (ACC). The activation of the Wnt/beta-catenin signaling is frequent in ACC and this pathway is a promising therapeutic target. AIM: To investigate the effects of the inhibition of the Wnt/beta-catenin in ACC cells. METHODS: Adrenal (NCI-H295 and Y1) and non-adrenal (HeLa) cell lines were treated with PNU-74654 (5-200 µM) for 24-96 h to assess cell viability (MTS-based assay), apoptosis (Annexin V), expression/localization of beta-catenin (qPCR, immunofluorescence, immunocytochemistry and western blot), expression of beta-catenin target genes (qPCR and western blot), and adrenal steroidogenesis (radioimmunoassay, qPCR and western blot). RESULTS: In NCI-H295 cells, PNU-74654 significantly decreased cell proliferation 96 h after treatment, increased early and late apoptosis, decreased nuclear beta-catenin accumulation, impaired CTNNB1/beta-catenin expression and increased beta-catenin target genes 48 h after treatment. No effects were observed on HeLa cells. In NCI-H295 cells, PNU-74654 decreased cortisol, testosterone and androstenedione secretion 24 and 48 h after treatment. Additionally, in NCI-H295 cells, PNU-74654 decreased SF1 and CYP21A2 mRNA expression as well as the protein levels of STAR and aldosterone synthase 48 h after treatment. In Y1 cells, PNU-74654 impaired corticosterone secretion 24 h after treatment but did not decrease cell viability. CONCLUSIONS: Blocking the Tcf/beta-catenin complex inhibits the Wnt/beta-catenin signaling in adrenocortical tumor cells triggering increased apoptosis, decreased cell viability and impairment of adrenal steroidogenesis. These promising findings pave the way for further experiments inhibiting the Wnt/beta-catenin pathway in pre-clinical models of ACC. The inhibition of this pathway may become a promising adjuvant therapy for patients with ACC.

Association between HIV infection and bone mineral density in climacteric women.

UNLABELLED: A cross-sectional study was conducted with the purpose of evaluating bone mineral density in HIV seropositive and seronegative climacteric women. HIV infection was negatively associated with bone mineral density in the lumbar spine PURPOSE: To assess bone mineral density (BMD) and its associated factors in HIV seropositive and seronegative climacteric women METHODS: A cross-sectional study with 537 women (273 HIV seropositive and 264 HIV seronegative) aged between 40 and 60 years old receiving follow-up care at two hospitals in Brazil. A questionnaire on clinical and sociodemographic characteristics was completed. Laboratory tests were performed, and BMD was measured at the lumbar spine and hip. Statistical analysis was carried out by Yates and Pearson chi-squared tests, Mann-Whitney test, and multiple linear regression. RESULTS: The mean age was 47.7 years in HIV-seropositive women, and 75 % had nadir CD4 above 200, and 77.8 % had viral load below the detection limit. The mean age in the HIV-seronegative women was 49.8 years. The prevalence of low spinal BMD was 14.6 % in the HIV-seropositive and 4.6 % in the HIV-seronegative women (p < 0.01). The prevalence of low BMD at the femoral neck was 5.6 % in HIV-seropositive and 3.3 % in the HIV-seronegative women (p = 0.38). Multiple analyses showed that the factors associated with lower BMD at the spine were being postmenopausal and being HIV-seropositive. Being overweight was associated with a higher BMD. At the femoral neck, factors associated with lower BMD were being postmenopausal and being white. Being overweight and having a greater number of pregnancies were associated with higher BMD CONCLUSIONS: HIV-seropositive women on long-term antiretroviral treatment and in good immunological conditions exhibited low BMD in the spine (L1-L4). However, BMD in the femoral neck was similar to non-infected women.