Hours of sleep and associated factors in college students during the COVID-19 pandemic.

BACKGROUND: Sleep alterations are common in college students, particularly during the COVID-19 pandemic. Sociodemographic factors may predict these alterations in this population. OBJECTIVE: To identify the sociodemographic factors and health characteristics associated with the number of hours of sleep of college students during the COVID-19 pandemic. METHODS: This was a cross-sectional study carried out with 244 university students from a multicampi public university in the State of Bahia, Northeast Brazil. Data collection was performed online and participants answered a specific questionnaire to assess sleep hours, sociodemographic and health variables. RESULTS: Significant associations were observed between hours of sleep and older students (odds ratio adjusted -ORaj: 3.75; 95% Confidence Interval -CI: 1.81-7.75; p < 0.01), attending the final semesters (ORaj: 1.85; 95% CI: 1.05-3.25; p < 0.03), and who reported having some disease (ORaj: 2.18; 95% CI: 1.05-4.50; p < 0.03) with greater chances of getting less sleep. However, those who used tobacco (ORaj: 0.08; 95% CI: 0.01-0.45; p < 0.001) were likely to have more hours of sleep per night. CONCLUSION: Sleep restriction was common among participating college students, which has likely intensified due to the COVID-19 pandemic and its restrictions. This encourages specific public health actions, contemplating the health and hours of sleep of this population.

Habilidades de comunicação clínica: análise da autoavaliação dos residentes de medicina de família e comunidade / Clinical communication skills: analysis of the self-assessment of family medicine residents

Resumo Introdução: O conhecimento das habilidades de comunicação clínica é primordial para o adequado exercício da medicina de família e comunidade (MFC), visto que um dos princípios da especialidade advém da relação médico-pessoa. A comunicação assertiva é uma competência clínica básica que deve ser aprendida, sobretudo, durante a residência médica. Não se trata de uma característica inata, perpassa um processo de conhecer, aplicar e dominar, necessitando, portanto, de avaliações. Objetivo: Este estudo teve como objetivo avaliar a percepção dos médicos residentes de MFC em relação às suas habilidades de comunicação. Método: Trata-se de um estudo quantitativo, descritivo e transversal. O cenário de estudo foi o conjunto de programas de residência de MFC do município de João Pessoa, na Paraíba. A coleta de dados foi feita a partir de um questionário on-line, disponível para preenchimento de setembro a novembro de 2022. Utilizamos para a construção do questionário o instrumento A Consulta em 7 Passos. Desenvolvemos escores denominados índice de desempenho geral (IDg), índice de desempenho por passo da consulta (IDp) e índice de desempenho por item (IDitem). Na análise estatística, utilizamos o teste t para amostras independentes. Resultado: O IDg médio foi de 72,0%. Os residentes tiveram o maior índice de IDp no passo 5 da consulta (81,7%), seguido pelos passos 2 (77,6%), 3 (76,1%) e 6 (75,9%). Os menores desempenhos foram nos passos 4 (68,9%), 7 (63,7%) e 1 (63,3%). Não houve significância estatística quanto ao desempenho quando se compararam sexo, ano de residência e programa. Conclusão: Os residentes de MFC avaliam positivamente suas habilidades de comunicação. Entretanto, ainda há o que aprimorar, como fomentar momentos crítico-reflexivos sobre os fenômenos subjetivos que ocorrem na consulta. Destarte, a utilização do instrumento A Consulta em 7 Passos se revelou, no presente estudo, como uma ferramenta importante no processo de formação e avaliação da comunicação clínica durante a residência.

Abstract Introduction: Knowledge of clinical communication skills is essential for the proper practice of Family Medicine, since one of the principles of the specialty treats the doctor-person relationship as fundamental. Good communication is a basic clinical competence and must be learned, above all, during medical residency. Communication is not an innate characteristic, but a process of self-knowledge, therefore requiring self-assessments. Objective: This study aimed to evaluate the perception of Family Medicine residents doctors in relation to their communication skills. Method: This is a quantitative, descriptive and cross-sectional study. The study setting was the set of Family Medicine Residency Programs in the city of João Pessoa, Paraíba. Data collection was performed using an online questionnaire, available to be completed from September to November 2022. We used the instrument A consulta em 7 passos (7-step consultation) to construct the questionnaire. We developed scores called overall performance index (IDg), query step performance index (IDp) and item performance index (IDitem). In the statistical analysis, we used the t test for independent samples. Result: The average overall performance index (IDg) was 72.0%. Residents had the highest IDp rate in step 5 of the consultation (81.7%), followed by step 2 (77.6%), step 3 (76.1%) and step 6 (75.9% ). While residents had the lowest performances in descending order in steps 4 (68.9%), 7 (63.7%) and 1 (63.3%). There was no statistical significance between sexes, year of residency and residency program. Conclusion: MFC residents positively evaluate their communication skills. However, there is still room forto improvement in how to encourage critical-reflective moments about the subjective phenomena that occur in the consultation. Furthermore, the use of a consulta em 7 passos is an important tool in the training and evaluation process in residency.

Rare Association of Autoimmune Limbic Encephalitis and Stiff Person Syndrome.

Antibodies to Glutamic Acid Decarboxylase (GAD) have been implicated in the pathogenesis of both autoimmune Limbic Encephalitis (LE) and Stiff Person Syndrome (SPS). However, their association is quite rare. We present a case of a 48-year-old Caucasian female who presented with symptoms of recurrent severe headaches, behavioral and cognitive dysfunction, and an episode of seizure. She was found to have high titers of anti-GAD65 antibodies in both cerebrospinal fluid and serum. She was diagnosed with LE and SPS, and was started on immunosuppressive therapy with steroids and intravenous immunoglobulins (IVIG). The patient responded well to treatment with improvement in her symptoms.

Comprehensive analysis of the GALACTINOL SYNTHASE (GolS) gene family in citrus and the function of CsGolS6 in stress tolerance.

Galactinol synthase (GolS) catalyzes the first and rate-limiting step in the synthesis of raffinose family of oligosaccharides (RFOs), which serve as storage and transport sugars, signal transducers, compatible solutes and antioxidants in higher plants. The present work aimed to assess the potential functions of citrus GolS in mechanisms of stress response and tolerance. By homology searches, eight GolS genes were found in the genomes of Citrus sinensis and C. clementina. Phylogenetic analysis showed that there is a GolS ortholog in C. clementina for each C. sinensis GolS, which have evolved differently from those of Arabidopsis thaliana. Transcriptional analysis indicated that most C. sinensis GolS (CsGolS) genes show a low-level tissue-specific and stress-inducible expression in response to drought and salt stress treatments, as well as to 'Candidatus Liberibacter asiaticus' infection. CsGolS6 overexpression resulted in improved tobacco tolerance to drought and salt stresses, contributing to an increased mesophyll cell expansion, photosynthesis and plant growth. Primary metabolite profiling revealed no significant changes in endogenous galactinol, but different extents of reduction of raffinose in the transgenic plants. On the other hand, a significant increase in the levels of metabolites with antioxidant properties, such as ascorbate, dehydroascorbate, alfa-tocopherol and spermidine, was observed in the transgenic plants. These results bring evidence that CsGolS6 is a potential candidate for improving stress tolerance in citrus and other plants.

Olhares do Internato Médico sob os Registros dos Atendimentos às Pessoas para além da Área Adstrita

Objetivos: pesquisa que se propõe a organizar os prontuários em saúde de moradores não adscritos à Unidade de Saúde da Família (USF) Saúde e Vida Integrada em João Pessoa-PB. A urbanização vertical adicionou usuários às equipes, pois uma morada se tornou várias, e as pessoas que passam a viver no território buscam a USF referência da comunidade. Existe inadequação do termo cotidiano "usuário fora de área", visto que ele habita o epicentro do território. Métodos: Trata-se de um relato de experiência que buscou narrar o cuidado ofertado para além do cadastro formal. Resultados e Discussão: Os registros dos atendimentos se deram através do Registro em Saúde Orientado por Problemas (ReSOAP), acompanhados de maio a setembro de 2019, sob os olhares dos internos de medicina da Universidade Federal da Paraíba (UFPB). A pesquisa teve como mote o esboço criativo-organizacional de fichas de atendimento organizadas cronologicamente, orientadas por problemas e separadas por famílias. Buscou-se, através dessa tecnologia leve, fornecer cuidado longitudinal, garantia de acompanhamento e seguimento. Ao desenvolver o Prontuário de Saúde da Família dessas pessoas consideradas "fora de área", procurou-se trabalhar com o postulado da coerência, transformando o atendimento individual, o motivo de consulta em um compilado de registros dos indivíduos adequado às necessidades da pessoa no seio da família. Conclusões: a idealização desse prontuário não formal propiciou organização e entusiasmo estudantil e foi utilizado como fonte para cuidados longitudinais, trazendo benefícios para a formação acadêmica e para a comunidade.

Effect of the execution order from concurrent exercise session on blood pressure responses in hypertensive older men

Abstract Aim: To compare blood pressure (BP) responses among the different orders of execution of concurrent exercise (CE) sessions in controlled hypertensive older men. Methods: Fifteen older men (64 ± 5 years) participated in three randomized crossover sessions: control session (C), CE in aerobic-resistance order (AR), and resistance-aerobic order (RA). The CE was performed for 1 h, in which 30 min were for the resistance exercise with 5 exercises at 70% of 1RM and 30 min for the aerobic exercise on a treadmill with intensity corresponding to the first ventilatory threshold. Clinical systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) were measured at rest and over 2 h and 24 h after the session. For analysis, the Generalized Estimating Equations (GEE) test was used with Bonferroni's complimentary test (α = 0.05). Results: The SBP decreased by 30 min after AR, while after RA we obtained reductions during 1 h after a session concerning rest. Between sessions, we found lower values in both CE compared to the C at 30 min, 45 min, and 90 min. In the RA there was a lower pressure in relation to the C at minute 60. The DBP reduced 30 min after the AR regarding the pre-session, however with no difference between sessions. The MBP was lower in relation to 30 min rest after AR. Among sessions, a pressure drop was observed in the AR compared to the C at 30 min and 45 min. Conclusion: We can conclude that the CE was effective in generating post-exercise hypotension regardless of the order in controlled hypertensive older men.

Metastatic Melanoma Progression Is Associated with Endothelial Nitric Oxide Synthase Uncoupling Induced by Loss of eNOS:BH4 Stoichiometry.

Melanoma is the most aggressive type of skin cancer due to its high capability of developing metastasis and acquiring chemoresistance. Altered redox homeostasis induced by increased reactive oxygen species is associated with melanomagenesis through modulation of redox signaling pathways. Dysfunctional endothelial nitric oxide synthase (eNOS) produces superoxide anion (O2-•) and contributes to the establishment of a pro-oxidant environment in melanoma. Although decreased tetrahydrobiopterin (BH4) bioavailability is associated with eNOS uncoupling in endothelial and human melanoma cells, in the present work we show that eNOS uncoupling in metastatic melanoma cells expressing the genes from de novo biopterin synthesis pathway Gch1, Pts, and Spr, and high BH4 concentration and BH4:BH2 ratio. Western blot analysis showed increased expression of Nos3, altering the stoichiometry balance between eNOS and BH4, contributing to NOS uncoupling. Both treatment with L-sepiapterin and eNOS downregulation induced increased nitric oxide (NO) and decreased O2• levels, triggering NOS coupling and reducing cell growth and resistance to anoikis and dacarbazine chemotherapy. Moreover, restoration of eNOS activity impaired tumor growth in vivo. Finally, NOS3 expression was found to be increased in human metastatic melanoma samples compared with the primary site. eNOS dysfunction may be an important mechanism supporting metastatic melanoma growth and hence a potential target for therapy.

Physical exercise is effective for neuropsychiatric symptoms in Alzheimer's disease: a systematic review / Exercício físico é efetivo para sintomas neuropsiquiátricos na doença de Alzheimer: uma revisão sistemática

ABSTRACT Background: Neuropsychiatric symptoms are disorders frequently seen in Alzheimer's disease. These symptoms contribute to reduction of brain reserve capacity and, in addition, they present unfavorable implications, such as: poor prognosis for the disease, increased functional decline, increased burden on the caregiver and institutionalization. This scenario makes neuropsychiatric symptoms one of the biggest problems in Alzheimer's disease, and gives rise to a need for treatments focused on improving these symptoms. Sow progress in drug trials has led to interest in exploring non-pharmacological measures for improving the neuropsychiatric symptoms of Alzheimer's disease, such as physical exercise. Objective: To ascertain the effect of exercise on the neuropsychiatric symptoms of Alzheimer's disease and its implications. Methods: This was a systematic review of effective longitudinal research, conducted by searching for articles in the PubMed, Web of Science, CINAHL and Scopus electronic databases, from 2009 to 2019. Studies in which the sample consisted of elderly people aged 65 years old or over with a diagnosis of Alzheimer's disease were included. Initially 334 articles were identified. After exclusions, 21 articles remained to be read in full. From these, five articles fitted the eligibility criteria, and a further two articles were added through manual searches in the references of the articles found. Results: Out of the seven articles analyzed in this review, five studies revealed that physical exercise had a positive effect on the neuropsychiatric symptoms of Alzheimer's disease. Conclusion: This systematic review indicated that physical exercise is a favorable non-pharmacological means for attenuating the neuropsychiatric symptoms of elderly people with Alzheimer's disease, with special attention to aerobic exercises.

RESUMO Introdução: Sintomas neuropsiquiátricos são desordens frequentemente observadas na Doença de Alzheimer, os quais contribuem para a diminuição da capacidade de reserva cerebral e ocasiona implicações ruins, como mau prognóstico da doença, aumento do declínio funcional, aumento da sobrecarga do cuidador e institucionalização. Esse cenário faz com que os sintomas neuropsiquiátricos se tornem um dos maiores problemas da Doença de Alzheimer, incitando, assim, o interesse em explorar medidas não-farmacológicas nos sintomas neuropsiquiátricos na Doença de Alzheimer, como o exercício físico. Objetivo: Verificar o efeito do exercício físico em sintomas neuropsiquiátricos da Doença de Alzheimer e suas implicações. Métodos: Trata-se de uma revisão sistemática com pesquisas longitudinais efetivadas por meio da busca de artigos nas bases de dados eletrônicas: PubMed, Web of Science, CINAHL e Scopus, de 2009 a 2019. Foram incluídos estudos cuja amostra foi constituída por idosos com diagnóstico de Doença de Alzheimer com idade igual ou acima de 65 anos. Inicialmente, foram identificados 334 artigos; após as exclusões, restaram 21 artigos para leitura na íntegra. Destes, cinco artigos se enquadraram nos critérios de elegibilidade, assim como dois artigos adicionados por meio de busca manual nas referências dos artigos encontrados. Resultados: Dos sete artigos analisados na presente revisão, cinco estudos revelaram um efeito positivo do exercício físico em sintomas neuropsiquiátricos na Doença de Alzheimer. Conclusão: Esta revisão sistemática indica que o exercício físico é um meio não-farmacológico favorável à atenuação dos sintomas neuropsiquiátricos de idosos com Doença de Alzheimer, com especial atenção na modalidade aeróbia.

ADAM17 cytoplasmic domain modulates Thioredoxin-1 conformation and activity.

The activity of Thioredoxin-1 (Trx-1) is adjusted by the balance of its monomeric, active and its dimeric, inactive state. The regulation of this balance is not completely understood. We have previously shown that the cytoplasmic domain of the transmembrane protein A Disintegrin And Metalloprotease 17 (ADAM17cyto) binds to Thioredoxin-1 (Trx-1) and the destabilization of this interaction favors the dimeric state of Trx-1. Here, we investigate whether ADAM17 plays a role in the conformation and activation of Trx-1. We found that disrupting the interacting interface with Trx-1 by a site-directed mutagenesis in ADAM17 (ADAM17cytoF730A) caused a decrease of Trx-1 reductive capacity and activity. Moreover, we observed that ADAM17 overexpressing cells favor the monomeric state of Trx-1 while knockdown cells do not. As a result, there is a decrease of cell oxidant levels and ADAM17 sheddase activity and an increase in the reduced cysteine-containing peptides in intracellular proteins in ADAM17cyto overexpressing cells. A mechanistic explanation that ADAM17cyto favors the monomeric, active state of Trx-1 is the formation of a disulfide bond between Cys824 at the C-terminal of ADAM17cyto with the Cys73 of Trx-1, which is involved in the dimerization site of Trx-1. In summary, we propose that ADAM17 is able to modulate Trx-1 conformation affecting its activity and intracellular redox state, bringing up a novel possibility for positive regulation of thiol isomerase activity in the cell by mammalian metalloproteinases.

Avaliação do autocuidado na adesão do tratamento em pacientes usuários de insulinas / Evaluation of self-care in adherence to treatment in patients using insulin

O tratamento do diabetes constituí em alterações no estilo de vida, através de atividades físicas, hábitos alimentares e quando necessário uso de medicamentos. O objetivo deste trabalho foi avaliar o autocuidado de pacientes com diabetes mellitus em uso de insulina. O estudo teve uma abordagem exploratória, descritiva, quantitativa, realizada através do Questionário de Atividades de Autocuidado com o Diabetes (QAD). A maioria dos entrevistados (40) foram mulheres, entre 50 a 59 anos, casadas, aposentadas e autodeclaradas brancos. O item que apresentou menor aderência foi a realização de atividade física e o de maior aderência foi a utilização dos medicamentos. Concluímos que a aderência ao autocuidado ainda é baixa, por ser pouco entendida pelos pacientes. A educação em saúde é uma ferramenta importante para compreender a doença e entender a importância de realizar um tratamento completo. A realização do acompanhamento por uma equipe multiprofissional, traz uma abordagem mais abrangente e efetiva.

The treatment of diabetes constitutes changes in lifestyle, through physical activities, eating habits and use of medications when necessary. The objective of this work was to evaluate self-care of patients with diabetes mellitus in insulin use. The study had an exploratory, descriptive, quantitative approach, carried out through the Diabetes Self-Care Activity Questionnaire. Most of the interviewees were women, 50-59 years, married, retired and self-declared white. The item that presented less adhesion was the physical activity and the one of greater adhesion was the use of the medications. We conclude that adherence to self-care is still low, because it is still poorly understood by patients. Health education is an important tool for understanding the disease and understanding the importance of completing treatment. The realization of this, by the multiprofessional team, brings a more comprehensive and effective approach.

Imbalance between nitric oxide and superoxide anion induced by uncoupled nitric oxide synthase contributes to human melanoma development.

Melanoma is the most aggressive type of cutaneous tumors due to its metastatic potential and high mortality. Increased levels of reactive oxygen species, including superoxide anion (O2-), and the consequent installation of a pro-oxidant environment are associated with melanoma development. The enzyme nitric oxide synthase (NOS), responsible for the production of nitric oxide (NO), when uncoupled is as a source of O2-, for example by the absence of its cofactor tetrahydrobiopterin (BH4). Western blot analysis showed increased expression of endothelial and inducible NOS in human melanoma cells, altering the stoichiometry between NOS levels and BH4 concentration and together with decreased BH4:BH2 ratio are contributing to NOS uncoupling. The treatment of melanoma cells with exogenous BH4 increased NO concentration and decreased O2- levels, leading to NOS coupling, which in turn reduced cell viability, cell proliferation and the ability of melanoma cells to form melanoma spheroids. Moreover, BH4 level restoration rendered melanoma cells more sensitive to apoptosis, demonstrating the role of dysfunctional NOS in melanoma genesis.

Thioredoxin-1 Negatively Modulates ADAM17 Activity Through Direct Binding and Indirect Reductive Activity.

AIMS: A disintegrin and metalloprotease 17 (ADAM17) modulates signaling events by releasing surface protein ectodomains such as TNFa and the EGFR-ligands. We have previously characterized cytoplasmic thioredoxin-1 (Trx-1) as a partner of ADAM17 cytoplasmic domain. Still, the mechanism of ADAM17 regulation by Trx-1 is unknown, and it has become of paramount importance to assess the degree of influence that Trx-1 has on metalloproteinase ADAM17. RESULTS: Combining discovery and targeted proteomic approaches, we uncovered that Trx-1 negatively regulates ADAM17 by direct and indirect effect. We performed cell-based assays with synthetic peptides and site-directed mutagenesis, and we demonstrated that the interaction interface of Trx-1 and ADAM17 is important for the negative regulation of ADAM17 activity. However, both Trx-1K72A and catalytic site mutant Trx-1C32/35S rescued ADAM17 activity, although the interaction with Trx-1C32/35S was unaffected, suggesting an indirect effect of Trx-1. We confirmed that the Trx-1C32/35S mutant showed diminished reductive capacity, explaining this indirect effect on increasing ADAM17 activity through oxidant levels. Interestingly, Trx-1K72A mutant showed similar oxidant levels to Trx-1C32/35S, even though its catalytic site was preserved. We further demonstrated that the general reactive oxygen species inhibitor, Nacetylcysteine (NAC), maintained the regulation of ADAM17 dependent of Trx-1 reductase activity levels; whereas the electron transport chain modulator, rotenone, abolished Trx-1 effect on ADAM17 activity. INNOVATION: We show for the first time that the mechanism of ADAM17 regulation, Trx-1 dependent, can be by direct interaction and indirect effect, bringing new insights into the cross-talk between isomerases and mammalian metalloproteinases. CONCLUSION: This unexpected Trx-1K72A behavior was due to more dimer formation and, consequently, the reduction of its Trx-1 reductase activity, evaluated through dimer verification, by gel filtration and mass spectrometry analysis. Antioxid. Redox Signal. 29, 717-734.

Sex steroids and metabolic responses in mussels Mytilus galloprovincialis exposed to drospirenone.

Drospirenone (DRO) is a synthetic progestin derived from 17α-spironolactone with a pharmacological mechanism of action similar to progesterone. Despite its wide use as pharmaceutical and consequent continuous release into the aquatic environment, DRO effects have been poorly investigated on aquatic biota. In order to unravel the toxicity mechanisms of DRO, mussels Mytilus galloprovincialis were exposed for 7 days to different concentrations of DRO, namely 20ng/L (Low; L), 200ng/L (Medium; M), 2000ng/L (High; H) and 10µg/L (Super High; SH) nominal doses. Following exposure, no significant effect was observed on gonad maturation of treated and untreated mussels. The levels of progesterone (P4) and testosterone (T) were measured in mantle/gonad tissues and no significant alteration detected after exposure. However, the application of a protonic nuclear magnetic resonance (1H NMR)-based metabolomics approach enabled a comprehensive assessment of DRO effects in mussels. Specifically, 1H NMR metabolic fingerprints of digestive glands of DRO treated mussel groups were clearly separated from each other and from controls through a principal component analysis (PCA). Moreover, a number of metabolites involved in different metabolic pathways were found to significantly change in DRO-exposed mussels compared to control, suggesting the occurrence of alterations in energy metabolism, amino acids metabolism, and glycerophospholipid metabolism. Overall, despite no changes in gonad maturation and steroids levels were recorded in mussels after DRO exposure, the metabolomics approach demonstrated its effectiveness and high sensitivity in elucidating DRO-induced metabolic disturbances in marine mussels, and thus its usefulness in the environmental risk assessment of pharmaceuticals.

A percepção de professores de educação infantil sobre a atuação fonoaudiológica na escola / The perception of kindergarten teachers about the speech therapist work at school / La percepción de los maestros de preescolar acerca de actuación fonoaudiológica en la escuela

Objetivo: Analisar a percepção de professores de educação infantil sobre a atuação do fonoaudiólogo na escola. Método: Pesquisa do tipo transversal com análise qualitativa. Foram realizadas entrevistas semiestruturadas com seis professoras de educação infantil e uma pedagoga de educação especial. Todo material coletado foi transcrito na íntegra e analisado, utilizando-se para isso a Análise de Conteúdo. Resultados: Nossos achados sugerem que este grupo de professoras apresenta um conhecimento restrito sobre quem é o profissional fonoaudiólogo e sobre sua atuação. O fonoaudiólogo ainda é visto como um especialista, um profissional da área da saúde que em ambiente escolar vai auxiliar o trabalho do professor, dizer como este deve proceder com os alunos que tenham alguma dificuldade na fala, ou que irá sanar tais dificuldades. As professoras veem a atuação fonoaudiológica como algo benéfico, com reflexos positivos, tanto para suas ações pedagógicas, como para seus alunos. Conclusão: Foi possível observar que a atuação fonoaudiológica na escola tem muito com o que contribuir e que a busca pelo trabalho em parceria é o caminho para se alcançar mudanças qualitativas tanto na equipe escolar como nos próprios alunos.

Purpose: To analyze the perception of kindergarten teachers on the performance of the speech therapist professional in the school. Method: Transversal study using qualitative analysis. Six teachers of child education and one teacher of special education participated in the study. Semi structuralized interviews have been carried through and all the collected data were transcribed and analyzed using for the Analysis of Content. Results: Our findings suggest that this group of teachers presents a restricted knowledge on who is the speech therapist professional and which is his/her area of performance. The speech therapist is still seen as a specialist, a professional of the health area that can assist the work of the teacher, who should proceed with the pupils who have some speech difficulties. The teachers see the speech therapist performance as beneficial with positive consequences for the pupil development. Conclusion: It has been observed that the speech therapist performance in the school has much to contribute and the search for a partnership with the teachers is the way to reach qualitative changes in the school team as in the children.

Objetivo: Analizar la percepción de profesores de educación infantil sobre la actuación del fonoaudiólogo en la escuela. Método: Investigación de tipo transversal con análisis cualitativo. Se realizaron entrevistas semiestructuradas con 6 profesoras de educación infantil y una pedagoga de educación especial. Todo el material fue transcrito integralmente y analizado utilizando el Análisis del Contenido. Resultados: Nuestros hallazgos sugieren que este grupo de profesoras presenta un conocimiento limitado sobre quién es el profesional fonoaudiólogo y su actuación. El fonoaudiólogo todavía es visto como un especialista, un profesional del área de la salud que en el ambiente escolar va a auxiliar el trabajo del profesor, decir como este debe proceder con los alumnos que tengan alguna dificultad en el habla, o irá a sanar tales dificultades. Las profesoras ven la actuación fonoaudiológica como algo benéfico, con reflejos positivos, tanto para sus acciones pedagógicas, como para sus alumnos. Conclusión: Se ha podido observar que la actuación fonoaudiológica en la escuela tiene mucho con lo que contribuir y que la búsqueda del trabajo en conjunto es el camino para alcanzar cambios cualitativos tanto en el equipo escolar como en los propios alumnos.

Induction of Oxidants Distinguishes Susceptibility of Prostate Carcinoma Cell Lines to p53 Gene Transfer Mediated by an Improved Adenoviral Vector.

Previously, the authors developed an adenoviral vector, Ad-PG, where transgene expression is regulated by a p53-responsive promoter. When used to transfer the p53 cDNA, a positive feedback mechanism is established. In the present study, a critical comparison is performed between Ad-PGp53 and AdRGD-PGp53, where the RGD motif was incorporated in the adenoviral fiber protein. AdRGD-PGp53 provided superior transgene expression levels and resulted in the killing of prostate carcinoma cell lines DU145 and PC3. In vitro, this effect was associated with increased production of cytoplasmic and mitochondrial oxidants, DNA damage as revealed by detection of phosphorylated H2AX, as well as cell death consistent with apoptosis. Differential gene expression of key mediators of reactive oxygen species pathways was also observed. Specifically, it was noted that induction of known p53-target genes Sestrin2 and PIG3, as well as a novel target, NOX1, occurred in PC3 cells only when transduced with the improved vector, AdRGD-PGp53. The participation of NOX1 was confirmed upon its inhibition using a specific peptide, resulting in reduced cell death. In situ gene therapy also resulted in significantly improved inhibition of tumor progression consistent with oxidant-induced DNA damage only when treated with the novel AdRGD-PGp53 vector. The study shows that the improved adenovirus overcomes limitations associated with other p53-expressing vectors and induces oxidant-mediating killing, thus supporting its further development for cancer gene therapy.

Nitroarachidonic acid (NO2AA) inhibits protein disulfide isomerase (PDI) through reversible covalent adduct formation with critical cysteines.

BACKGROUND: Nitroarachidonic acid (NO2AA) exhibits pleiotropic anti-inflammatory actions in a variety of cell types. We have recently shown that NO2AA inhibits phagocytic NADPH oxidase 2 (NOX2) by preventing the formation of the active complex. Recent work indicates the participation of protein disulfide isomerase (PDI) activity in NOX2 activation. Cysteine (Cys) residues at PDI active sites could be targets for NO2AA- nitroalkylation regulating PDI activity which could explain our previous observation. METHODS: PDI reductase and chaperone activities were assessed using the insulin and GFP renaturation methods in the presence or absence of NO2AA. To determine the covalent reaction with PDI as well as the site of reaction, the PEG-switch assay and LC-MS/MS studies were performed. RESULTS AND CONCLUSIONS: We determined that both activities of PDI were inhibited by NO2AA in a dose- and time- dependent manner and independent from release of nitric oxide. Since nitroalkenes are potent electrophiles and PDI has critical Cys residues for its activity, then formation of a covalent adduct between NO2AA and PDI is feasible. To this end we demonstrated the reversible covalent modification of PDI by NO2AA. Trypsinization of modified PDI confirmed that the Cys residues present in the active site a' of PDI were key targets accounting for nitroalkene modification. GENERAL SIGNIFICANCE: PDI may contribute to NOX2 activation. As such, inhibition of PDI by NO2AA might be involved in preventing NOX2 activation. Future work will be directed to determine if the covalent modifications observed play a role in the reported NO2AA inhibition of NOX2 activity.

Characterization of quality of sediments from Paranaguá Bay (Brazil) by combined in vitro bioassays and chemical analyses.

The present study characterizes the quality of sediments from the Paranaguá Estuarine Complex (South Brazil). Polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs) were determined in sediment samples together with a series of different in vitro bioassays. The fish hepatoma cell line (PLHC-1) was used to determine the presence of cytotoxic compounds and CYP1A- and oxidative stress-inducing agents in sediment extracts. Ovarian microsomal fractions from sea bass (Dicentrarchus labrax) were used to detect the presence of endocrine disrupters that interfered with the synthesis of estrogens (ovarian CYP19). Despite the relatively low levels of pollutants and no evidence of negative effects based on guideline levels, sediments collected close to harbors were enriched with CYP1A-inducing agents and they showed higher cytotoxicity. In contrast, sediments from internal areas inhibited CYP19 activity, which suggests the presence of endocrine disrupters at these sites. Overall, the selected bioassays and the chemistry data led to the identification of potentially impacted areas along the Paranaguá Estuarine Complex that would require further action to improve their environmental quality. Environ Toxicol Chem 2017;36:1811-1819. © 2016 SETAC.

Comparative toxicity, oxidative stress and endocrine disruption potential of plasticizers in JEG-3 human placental cells.

Plasticizers are suspected to be toxic and/or to modulate or disrupt the endocrine system of humans and to cross the placental barrier, being embryonic and fetal development a particularly vulnerable period. This work investigates the comparative toxicity and ability to interfere with the synthesis of steroids and to generate reactive oxygen species (ROS) of a selected number of plasticizers, including bisphenol A (BPA), nonyl- (NP) and octylphenol (OP), benzyl butyl phthalate (BBP), dibutyl phthalate (DBP), di(2-ethylhexyl)phthalate (DEHP) and dimethyl phthalate (DMP), in the human placenta JEG-3 cells. Moreover, the bioavailability of chemicals in culture medium has been investigated. After 24h exposure, OP and NP showed the highest cytotoxicity (EC50: 36-40µM) followed by BPA (138-219µM), whereas no significant toxicity was observed for phthalates. Notwithstanding, BBP and DBP significantly decreased P450 aromatase activity (experimental IC50: 14-15µM), while NP and OP (20µM) increased the activity. Overall, this study evidences the differential toxicity and ability to modulate placental aromatase activity of some of the compounds nowadays used as plasticizers, and highlights the need of an accurate determination of the bioavailability of chemicals to improve the sensitivity of in-vitro tests.

Multisystemic eosinophilic epitheliotropic disease in a horse in Brazil / Doença multissistêmica eosinofílica epiteliotrópica em um eqüino no Brasil

ABSTRACT: Equine multisystemic eosinophilic epitheliotropic disease (MEED) is a rare disease, characterized by eosinophilia and eosinophilic infiltration of several organs. A 5-year-old horse presented pruritus, areas of alopecia, and moderate eosinophilia. The horse was treated with corticosteroids and antibiotics without substantial improvement; and after the disease progressed to fever, diarrhea, gastric reflux and progressive weight loss. Due to poor prognosis the horse was euthanized. Necropsy revealed poor body condition, multiple to coalescing foci of alopecia, with epidermal ulcerations and crusts on the head and distal parts of the limbs. The proximal duodenum was enlarged, with 3 intraluminal nodules. Histopathological evaluation revealed eosinophilic granulomas in the skin, oral mucosa, duodenum, pancreas, and mesenteric lymph nodes, which were associated with infiltrates of eosinophils, lymphocytes, macrophages, multinucleated giant cells, and occasional plasma cells, along with fibrovascular connective tissue proliferation. MEED should be included in the differential diagnosis of horses with skin lesions concomitant with clinical signs of gastrointestinal illness.

RESUMO: Doença multissistêmica eosinofílica epiteliotrópica (DMEE) dos equinos é uma doença rara que se caracteriza por eosinofilia e infiltrado de eosinófilos em vários órgãos. Um equino com cinco anos de idade apresentou prurido, áreas de alopecia e eosinofilia moderada. O equino foi tratado com corticosteroides e antibióticos sem melhora clínica significativa, com evolução para febre, diarreia, refluxo gástrico e emagrecimento progressivo. Devido ao prognóstico desfavorável, o equino foi eutanasiado. Na necropsia, apresentou condição corporal ruim, áreas multifocais a coalescentes de alopecia, ulceração da epiderme e crostas na cabeça e parte distal dos membros. A região proximal do duodeno estava aumentada de volume e apresentou três nódulos intraluminais. No exame histopatológico foram observados granulomas eosinofílicos associados a infiltrado de eosinófilos, linfócitos, macrófagos, células gigantes multinucleadas, ocasionais plasmócitos e proliferação de tecido conjuntivo fibroso na pele, mucosa oral, duodeno, pâncreas e linfonodos mesentéricos. DMEE deve ser considerada um diagnóstico diferencial em equinos que apresentem concomitantemente lesões cutâneas e sinais de doença gastrointestinal.

Modulation of MAPK and NF-954;B Signaling Pathways by Antioxidant Therapy in Skeletal Muscle of Heart Failure Rats.

BACKGROUND/AIMS: Although increased oxidative stress plays a role in heart failure (HF)-induced skeletal myopathy, signaling pathways involved in muscle changes and the role of antioxidant agents have been poorly addressed. We evaluated the effects of N-acetylcysteine (NAC) on intracellular signaling pathways potentially modulated by oxidative stress in soleus muscle from HF rats. METHODS AND RESULTS: Four months after surgery, rats were assigned to Sham, myocardial infarction (MI)-C (without treatment), and MI-NAC (treated with N-acetylcysteine) groups. Two months later, echocardiogram showed left ventricular dysfunction in MI-C; NAC attenuated diastolic dysfunction. Oxidative stress was evaluated in serum and soleus muscle; malondialdehyde was higher in MI-C than Sham and did not differ between MI-C and MI-NAC. Oxidized glutathione concentration in soleus muscle was similar in Sham and MI-C, and lower in MI-NAC than MI-C (Sham 0.168 ± 0.056; MI-C 0.223 ± 0.073; MI-NAC 0.136 ± 0.023 nmol/mg tissue; p = 0.014). Western blot showed increased p-JNK and decreased p38, ERK1/2, and p-ERK1/2 in infarcted rats. NAC restored ERK1/2. NF-954;B p65 subunit was reduced; p-Ser276 in p65 and I954;B was increased; and p-Ser536 unchanged in MI-C compared to Sham. NAC did not modify NF-954;B p65 subunit, but decreased p-Ser276 and p-Ser536. CONCLUSION: N-acetylcysteine modulates MAPK and NF-954;B signaling pathways in soleus muscle of HF rats.