Impact of the immune profiles of hypertensive patients with and without obesity on COVID-19 severity.

BACKGROUND: Comorbidities such as obesity, hypertension, and diabetes are associated with COVID-19 development and severity, probably due to immune dysregulation; however, the mechanisms underlying these associations are not clear. The immune signatures of hypertensive patients with obesity with COVID-19 may provide new insight into the mechanisms of immune dysregulation and progression to severe disease in these patients. METHODS: Hypertensive patients were selected prospectively from a multicenter registry of adults hospitalized with COVID-19 and stratified according to obesity (BMI ≥ 30 kg/m²). Clinical data including baseline characteristics, complications, treatment, and 46 immune markers were compared between groups. Logistic regression was performed to identify variables associated with the risk of COVID-19 progression in each group. RESULTS: The sample comprised 213 patients (89 with and 124 without obesity). The clinical profiles of patients with and without obesity differed, suggesting potential interactions with COVID-19 severity. Relative to patients without obesity, patients with obesity were younger and fewer had cardiac disease and myocardial injury. Patients with obesity had higher EGF, GCSF, GMCSF, interleukin (IL)-1ra, IL-5, IL-7, IL-8, IL-15, IL-1ß, MCP 1, and VEGF levels, total lymphocyte counts, and CD8+ CD38+ mean fluorescence intensity (MFI), and lower NK-NKG2A MFI and percentage of CD8+ CD38+ T cells. Significant correlations between cytokine and immune cell expression were observed in both groups. Five variables best predicted progression to severe COVID-19 in patients with obesity: diabetes, the EGF, IL-10, and IL-13 levels, and the percentage of CD8+ HLA-DR+ CD38+ cells. Three variables were predictive for patients without obesity: myocardial injury and the percentages of B lymphocytes and HLA-DR+ CD38+ cells. CONCLUSION: Our findings suggest that clinical and immune variables and obesity interact synergistically to increase the COVID-19 progression risk. The immune signatures of hypertensive patients with and without obesity severe COVID-19 highlight differences in immune dysregulation mechanisms, with potential therapeutic applications.

New Insights on the Mechanisms of Myocardial Injury in Hypertensive Patients With COVID-19.

PURPOSE: Myocardial injury is common in hypertensive patients with 2019 coronavirus disease (COVID-19). Immune dysregulation could be associated to cardiac injury in these patients, but the underlying mechanism has not been fully elucidated. METHODS: All patients were selected prospectively from a multicenter registry of adults hospitalized with confirmed COVID-19. Cases had hypertension and myocardial injury, defined by troponin levels above the 99th percentile upper reference limit, and controls were hypertensive patients with no myocardial injury. Biomarkers and immune cell subsets were quantified and compared between the two groups. A multiple logistic regression model was used to analyze the associations of clinical and immune variables with myocardial injury. RESULTS: The sample comprised 193 patients divided into two groups: 47 cases and 146 controls. Relative to controls, cases had lower total lymphocyte count, percentage of T lymphocytes, CD8+CD38+ mean fluorescence intensity (MFI), and percentage of CD8+ human leukocyte antigen DR isotope (HLA-DR)+ CD38-cells and higher percentage of natural killer lymphocytes, natural killer group 2A (NKG2A)+ MFI, percentage of CD8+CD38+cells, CD8+HLA-DR+MFI, CD8+NKG2A+MFI, and percentage of CD8+HLA-DR-CD38+cells. On multivariate regression, the CD8+HLA-DR+MFI, CD8+CD38+MFI, and total lymphocyte count were associated significantly with myocardial injury. CONCLUSION: Our findings suggest that lymphopenia, CD8+CD38+MFI, and CD8+HLA-DR+MFI are immune biomarkers of myocardial injury in hypertensive patients with COVID-19. The immune signature described here may aid in understanding the mechanisms underlying myocardial injury in these patients. The study data might open a new window for improvement in the treatment of hypertensive patients with COVID-19 and myocardial injury.

Structural alteration of cocoa bean shell fibers through biological treatment using Penicillium roqueforti.

Lignocellulosic residues, such as cocoa bean shell (FI), are generated in large quantities during agro-industrial activities. Proper management of residual biomass through solid state fermentation (SSF) can be effective in obtaining value-added products. The hypothesis of the present work is that the bioprocess promoted by P. roqueforti can lead to structural changes in the fibers of the fermented cocoa bean shell (FF) that confer characteristics of industrial interest. To unveil such changes, the techniques of FTIR, SEM, XRD, TGA/TG were used. After SSF, an increase of 36.6% in the crystallinity index was observed, reflecting the reduction of amorphous components such as lignin in the FI residue. Furthermore, an increase in porosity was observed through the reduction of the 2θ angle, which gives the FF a potential candidate for applications of porous products. The FTIR results confirm the reduction in hemicellulose content after SSF. The thermal and thermogravimetric tests showed an increase in the hydrophilicity and thermal stability of FF (15% decomposition) in relation to the by-product FI (40% decomposition). These data provided important information regarding changes in the crystallinity of the residue, existing functional groups and changes in degradation temperatures.

This work presents a new approach for solid state fermentation based on the study of structural changes caused by Penicillium roquefort, which is important to understand the changes in the lignocellulosic matrix after the fungus growth. The results provided important information regarding changes in the crystallinity of the residue, existing functional groups and changes in degradation temperatures. Consequently, they can help in proposals for the total use of the residual solid after fermentation, as well as contribute to reducing the lack of this information in the literature.

Troponin in COVID-19: To Measure or Not to Measure? Insights from a Prospective Cohort Study.

Myocardial injury (MI), defined by troponin elevation, has been associated with increased mortality and adverse outcomes in patients with coronavirus disease 2019 (COVID-19), but the role of this biomarker as a risk predictor remains unclear. Data from adult patients hospitalized with COVID-19 were recorded prospectively. A multiple logistic regression model was used to quantify associations of all variables with in-hospital mortality, including the calculation of odds ratios (ORs) and confidence intervals (CI). Troponin measurement was performed in 1476 of 4628 included patients, and MI was detected in 353 patients, with a prevalence of 23.9%; [95% CI, 21.8-26.1%]. The total in-hospital mortality rate was 10.9% [95% CI, 9.8-12.0%]. The mortality was much higher among patients with MI than among those without MI, with a prevalence of 22.7% [95% CI, 18.5-27.3%] vs. 5.5% [95% CI, 4.3-7.0%] and increased with each troponin level. After adjustment for age and comorbidities, the model revealed that the mortality risk was greater for patients with MI [OR = 2.99; 95% CI, 2.06-4.36%], and for those who did not undergo troponin measurement [OR = 2.2; 95% CI, 1.62-2.97%], compared to those without MI. Our data support the role of troponin as an important risk predictor for these patients, capable of discriminating between those with a low or increased mortality rate. In addition, our findings suggest that this biomarker has a remarkable negative predictive value in COVID-19.

Effect of tetrahydroquinoline derivatives on the intracellular Ca2+ homeostasis in breast cancer cells (MCF-7) and its relationship with apoptosis / Efecto de derivados de tetrahidroquinolinas sobre la homeostasis del Ca2+ intracelular en células de cáncer de mama (MCF-7) y su relación con la apoptosis

Abstract Tetrahydroquinoline derivatives are interesting structures exhibiting a wide range of biological activities, including antitumor effects. In this investigation, the effect of the synthesized tetrahydroquinolines JS-56 and JS-92 on apoptosis, intracellular Ca2+ concentration ([Ca2+]i), and the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) activity was determined on MCF-7 breast cancer cells. Colorimetric assays were used to assess MCF-7 cells viability and SERCA activity. Fura-2 and rhodamine 123 were used to measure the intracellular Ca2+ concentration and the mitochondrial electrochemical potential, respec tively. TUNEL assay was used to analyze DNA fragmentation, while caspase activity and NF-κB-dependent gene expression were assessed by luminescence. In silico models were used for molecular docking analysis. These compounds increase intracellular Ca2+ concentration; the main contribution is the Ca2+ entry from the extracellular milieu. Both JS-56 and JS-92 inhibit the activity of SERCA and dissipate the mitochondrial electrochemical potential through processes dependent and independent of the Ca2+ uptake by this organelle. Furthermore, JS-56 and JS-92 generate cytotoxicity in MCF-7 cells. The effect of JS-92 is higher than JS-56. Both compounds activate caspases 7 and 9, cause DNA fragmentation, and potentiate the effect of phorbol 12-myristate-13-acetate on NF-κB-dependent gene expression. Molecular docking analysis suggests that both compounds have a high interaction for SERCA, similar to thapsigargin. Both tetrahydroquinoline derivatives induced cell death through a combination of apoptotic events, increase [Ca2+]i, and inhibit SERCA activity by direct interaction.

Resumen Los derivados de tetrahidroquinolina son estructuras interesantes que exhiben una amplia gama de actividades biológicas, incluyendo efectos antitumorales. Se determinó el efecto de las tetrahidroquinolinas sintetizadas JS-56 y JS-92 sobre la apoptosis, concentración intracelular de Ca2+ ([Ca2+]i) y la actividad Ca2+-ATPasa del retículo sarco(endo)plásmico (SERCA) en células de cáncer de mama MCF-7. Se usaron ensayos colorimétricos para evaluar la viabilidad de las células MCF-7 y la actividad SERCA. Se emplearon Fura-2 y rodamina 123 para medir la concentración de Ca2+ intracelular y el potencial electroquímico mitocondrial, respectivamente. El ensayo TUNEL se utilizó para analizar la fragmentación del ADN, mientras que la actividad de caspasas y la expresión génica dependiente de NF-κB se evaluaron mediante luminiscencia. Modelos in silico permitieron el análisis del acoplamiento molecular. Estos compuestos aumentan la concentración de Ca2+ intracelular; la principal contribución es la entrada de Ca2+ desde el medio extracelular. Tanto JS-56 como JS-92 inhiben la actividad de SERCA y disipan el potencial electroquímico mitocondrial a través de procesos dependientes e independientes de la captación de Ca2+ por este orgánulo. Además, JS-56 y JS-92 generan citotoxicidad en células MCF-7. El efecto de JS-92 es mayor que JS-56. Ambos compuestos activan las caspasas 7 y 9, provocan la fragmentación del ADN y potencian el efecto del 12-miristato-13-acetato de forbol en la expresión génica dependiente de NF-κB. El análisis de acoplamiento molecular sugiere que ambos compuestos tienen una alta interacción con SERCA, similar a la tapsigargina. Ambos derivados de tetrahidroquinolina indujeron la muerte celular a través de una combinación de eventos apoptóticos, aumento de [Ca2+]i e inhibición de la actividad SERCA por interacción directa.

A Inclusão no Ensino Superior: Vivências de Estudantes com Deficiência Visual / The Challenge of Inclusion in Higher Education: Experiences of Students with Visual Impairment

RESUMO: Este artigo analisa o ponto de vista dos/as estudantes com deficiência visual sobre o seu ingresso e a sua permanência na Universidade Federal da Bahia (UFBA) e busca refletir sobre o processo de inclusão por eles/as vivenciado. Trata-se de uma pesquisa qualitativa realizada por meio de entrevistas semiestruturadas com oito estudantes com deficiência visual matriculados/as em diferentes cursos dessa instituição. A análise do material textual demonstrou que o ingresso e a permanência no Ensino Superior foram marcados por dificuldades relacionadas às barreiras físicas, à disponibilidade e ao acesso a recursos materiais, didáticos, pedagógicos e tecnológicos, bem como às barreiras atitudinais, que agudizam o desempenho acadêmico dos/as estudantes com deficiência visual. Desse modo, a inclusão educacional, em processo de construção na UFBA, requer envolvimento e participação de toda a comunidade acadêmica para que de fato se concretize.

ABSTRACT: This paper analyzes the point of view of students with visual impairment on their admission and permanence at the Universidade Federal da Bahia (UFBA), Brazil, and seeks to reflect on the inclusion process experienced by them. This is a qualitative investigation which was carried out through semi-structured interviews with eight students with visual impairment enrolled in different courses of this institution. The analysis of the collected material demonstrated that access to and permanence in Higher Education were characterized by difficulties related to physical barriers, availability, and access to didactic, pedagogical, and technological resources, as well as attitudinal barriers, which exacerbate the academic performance of students with visual impairment. Therefore, the educational inclusion, which is being built in UFBA, requires the involvement and participation of the entire academic community so that it is actually implemented.

Effect of Discontinuing vs Continuing Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on Days Alive and Out of the Hospital in Patients Admitted With COVID-19: A Randomized Clinical Trial.

Importance: It is unknown whether angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) have a positive, neutral, or negative effect on clinical outcomes in patients with coronavirus disease 2019 (COVID-19). Objective: To determine whether discontinuation compared with continuation of ACEIs or ARBs changed the number of days alive and out of the hospital through 30 days. Design, Setting, and Participants: A randomized clinical trial of 659 patients hospitalized in Brazil with mild to moderate COVID-19 who were taking ACEIs or ARBs prior to hospitalization (enrolled: April 9-June 26, 2020; final follow-up: July 26, 2020). Interventions: Discontinuation (n = 334) or continuation (n = 325) of ACEIs or ARBs. Main Outcomes and Measures: The primary outcome was the number of days alive and out of the hospital through 30 days. Secondary outcomes included death, cardiovascular death, and COVID-19 progression. Results: Among 659 patients, the median age was 55.1 years (interquartile range [IQR], 46.1-65.0 years), 14.7% were aged 70 years or older, 40.4% were women, and 100% completed the trial. The median time from symptom onset to hospital admission was 6 days (IQR, 4-9 days) and 27.2% of patients had an oxygen saturation of less than 94% of room air at baseline. In terms of clinical severity, 57.1% of patients were considered mild at hospital admission and 42.9% were considered moderate. There was no significant difference in the number of days alive and out of the hospital in patients in the discontinuation group (mean, 21.9 days [SD, 8 days]) vs patients in the continuation group (mean, 22.9 days [SD, 7.1 days]) and the mean ratio was 0.95 (95% CI, 0.90-1.01). There also was no statistically significant difference in death (2.7% for the discontinuation group vs 2.8% for the continuation group; odds ratio [OR], 0.97 [95% CI, 0.38-2.52]), cardiovascular death (0.6% vs 0.3%, respectively; OR, 1.95 [95% CI, 0.19-42.12]), or COVID-19 progression (38.3% vs 32.3%; OR, 1.30 [95% CI, 0.95-1.80]). The most common adverse events were respiratory failure requiring invasive mechanical ventilation (9.6% in the discontinuation group vs 7.7% in the continuation group), shock requiring vasopressors (8.4% vs 7.1%, respectively), acute myocardial infarction (7.5% vs 4.6%), new or worsening heart failure (4.2% vs 4.9%), and acute kidney failure requiring hemodialysis (3.3% vs 2.8%). Conclusions and Relevance: Among patients hospitalized with mild to moderate COVID-19 and who were taking ACEIs or ARBs before hospital admission, there was no significant difference in the mean number of days alive and out of the hospital for those assigned to discontinue vs continue these medications. These findings do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with mild to moderate COVID-19 if there is an indication for treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT04364893.

Inclusão educacional da pessoa com deficiência visual no ensino superior / Educational inclusion for visually impaired persons in the higher education

Resumo Introdução O número de estudantes com deficiência visual que ingressam no ensino superior tem sido expressivo graças às políticas de ações afirmativas e às mudanças na educação básica destinadas a este grupo nos últimos anos. Em vista dessas mudanças, o acesso à informação e as condições de acessibilidade disponibilizadas nas Instituições de Ensino Superior devem ser prioridades para garantir a permanência desses estudantes na universidade. Objetivo Analisar a produção científica sobre a inclusão educacional das pessoas com deficiência visual, especificamente no que diz respeito à permanência em instituições de ensino superior. Método Revisão integrativa realizada nos ambientes virtuais de acesso público, como o Portal de Periódicos da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) e a Scientific Electronic Library Online (SciELO), combinando os seguintes descritores: baixa visão, ensino superior, cegueira, acessibilidade, tecnologia assistiva e deficiência visual. Resultados 21 artigos foram selecionados, organizados e submetidos à análise, possibilitando a identificação de uma categoria: acesso e permanência de estudantes com deficiência visual no ensino superior; e duas subcategorias: formação docente para atuação com estudantes com deficiência visual; disponibilidade de recursos materiais nas instituições de ensino superior. Conclusão A análise do material indica que, embora o acesso ao ensino superior das pessoas com deficiência esteja legalmente amparado, é necessária uma efetiva inclusão desses estudantes nas instituições, evidenciando que não basta apenas possibilitar o ingresso, se não houver estruturas físicas adequadas e recursos materiais disponíveis e acessíveis que garantam a permanência do estudante com deficiência visual.

Abstract Introduction The number of students with visual impairment that have enrolled in higher education has been significant in recent years thanks to positive political action and designated changes in basic education. For that reason, access to information and accessibility conditions must be a priority, to ensure the continuation of these students within the university. Objective To analyze the scientific production on educational inclusion of the visually impaired, specifically concerning the continuation within higher education institutions. Method Integrated literature review in publicly accessible virtual environments, such as Brazil's Coordination for the Improvement of Higher Education Personnel (CAPES) and Scientific Electronic Library Online (SciELO), by combining the following descriptors: baixa visão, ensino superior, cegueira, acessibilidade, tecnologia assistiva e deficiência visual. Results 21 articles were identified, organized, and analyzed, enabling the identification of one category: access and continuation of visually impaired students within higher education; and two subcategories: teacher training aimed at working with visually impaired students and availability of material resources at higher education institutions. Conclusion The analysis of the resources indicates that, although access to higher education for people with disabilities is legally protected, actual inclusion is necessary within institutions. Hence, providing access is not enough if there are no suitable physical and material infrastructures to guarantee the continuation of the visually impaired student within the university.

A experiência do adoecimento na universidade: narrativas de estudantes do campo da saúde / La experiencia de enfermarse en la universidad: narraciones de estudiantes del campo de la salud / The illness experience at university: narratives of students from the health field

As questões que fazem parte do cotidiano da vida estudantil não se limitam aos modos por eles adotados para se adaptarem à vida acadêmica, mas envolvem também hábitos e mudanças relacionadas à saúde. Nesse sentido, o objetivo deste estudo foi analisar a experiência do adoecimento de estudantes do Bacharelado Interdisciplinar em Saúde (BI em Saúde) da Universidade Federal da Bahia (UFBA). Trata-se de um estudo orientado pela abordagem qualitativa, optando-se pela técnica da entrevista narrativa. A pesquisa foi realizada com estudantes que adoeceram durante a formação acadêmica. Por meio das narrativas, foi possível perceber que a experiência do adoecimento foi mediada pela formação em saúde e pela instituição universitária, que assume dois papéis: favorece os adoecimentos, mas também possibilita aos estudantes conhecimento e reflexão acerca do processo saúde-doença e cuidado.(AU)

Las cuestiones que forman parte del cotidiano de la vida estudiantil no se limitan a los modos adoptados por ellos para adaptarse a la vida académica, sino que también envuelven hábitos y cambios relacionados a la salud. En este sentido, el objetivo del estudio fue analizar la experiencia de la enfermedad por parte de estudiantes del Bachiller Interdisciplinario en Salud de la Universidad Federal de Bahia. Se trata de un estudio orientado por el abordaje cualitativo, optándose por la técnica de la entrevista narrativa. La investigación se realizó con estudiantes que se enfermaron durante su formación académica. Por medio de sus narraciones fue posible percibir que la experiencia de enfermarse fue medida por la formación en salud y por la institución universitaria que asume dos papeles: es un lugar que favorece las enfermedades, pero también es un espacio que posibilita a los alumnos conocimiento y reflexión sobre el proceso salud-enfermedad y cuidado.(AU)

Issues that are part of students' daily life are not limited to the ways in which they adapt to academic life; they also involve habits and changes related to health. The objective of this study was to analyze the illness experience of students enrolled in the Interdisciplinary Bachelor's Degree in Health of the Federal University of Bahia. It is a qualitative study that used the technique of narrative interview. The research was carried out with students who became ill during academic education. Through the narratives, it was possible to perceive that the illness experience was mediated by health education and by the university institution, which plays two roles: it is a place that favors the contraction of diseases, but it is also a space that provides students with knowledge and reflection on the health-disease process and care.(AU)

Formação em nutrição no Brasil: análise de alcances e limites a partir de uma revisão da literatura / Nutrition training in Brazil: analysis of scope and limits and a literature review / Formación en nutrición en Brasil: análisis de alcances y límites a partir de una revisión de la literatura

A formação em saúde é alvo de interesse nas pesquisas cujos resultados apontam para a necessidade de mudanças. O artigo apresenta um panorama atual da formação em nutrição por meio de uma revisão de literatura. A pesquisa foi realizada na Biblioteca Virtual em Saúde (BVS), nas bases de dados LILACS e SciELO no período entre 2000 e 2015, através dos descritores "formação and nutricionistas", "formação profissional and nutricionistas" e "formação em recursos humanos and nutricionistas". Parte considerável dos 15 artigos reflete sobre as limitações na formação em nutrição, tais como: escasso diálogo com as ciências humanas; incipiente articulação entre teoria e prática; ênfase no biologicismo e tecnicismo. O material apresenta, também, propostas para a superação dos limites apontados. Com base nesses aspectos, estratégias estão sendo implementadas para enfrentar os principais problemas identificados atualmente na formação de recursos humanos em saúde.

The matter of training in the field of health has caught the interest of research, whose results show a need for reform. This paper presents an overview of training in the field of nutrition at a national level, through a literature review. The search was carried out in the Virtual Library of Health (BVS) in the databases LILACS and SciELO regarding the period 2000­2015 with use of the keywords "formação AND nutricionistas", "formação profissional AND nutricionistas" and "formação AND recursos humanos and nutricionistas". Most of the 15 papers reflect about the limitations of training in nutrition, such as the lack of dialogue with soft sciences, the incipient collaboration between theory and practice, and the emphasis on biologicism and technicalities. They also present proposals to overcome the aforementioned limitations. On this basis, strategies are being implemented to tackle the main problems that have been identified in the area of human resource training in healthcare.

La formación en salud es objeto de interés en las investigaciones cuyos resultados apuntan a la necesidad de cambios. El artículo presenta un panorama actual de la formación en Nutrición por medio de una revisión de literatura. Se realizó una búsqueda en la Biblioteca Virtual en Salud (BVS), en las bases de datos LILACS y SciELO en el período entre 2000 y 2015, utilizando los descriptores "formación and nutricionistas", "formación profesional and nutricionistas" y "formación en recursos humanos and nutricionistas". Parte considerable de los 15 artículos refleja sobre las limitaciones en la formación en Nutrición, tales como: escaso diálogo con las ciencias humanas; incipiente articulación entre teoría y práctica; y énfasis en el biologicismo y el tecnicismo. El material presenta también propuestas para la superación de los límites apuntados. Con base en estos aspectos, se están implementando estrategias para enfrentar los principales problemas identificados actualmente en la formación de recursos humanos en salud.

Sphingosine inhibits the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) activity.

The increase in the intracellular Ca(2+) concentration ([Ca(2+)]i) is the key variable for many different processes, ranging from regulation of cell proliferation to apoptosis. In this work we demonstrated that the sphingolipid sphingosine (Sph) increases the [Ca(2+)]i by inhibiting the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), in a similar manner to thapsigargin (Tg), a specific inhibitor of this Ca(2+) pump. The results showed that addition of sphingosine produced a release of Ca(2+) from the endoplasmic reticulum followed by a Ca(2+) entrance from the outside mileu. The results presented in this work support that this sphingolipid could control the activity of the SERCA, and hence sphingosine may participate in the regulation of [Ca(2+)]I in mammalian cells.

L-arginine-nitric oxide pathway and oxidative stress in plasma and platelets of patients with pre-eclampsia.

Pre-eclampsia (PE), a syndrome of pregnancy-induced hypertension, continues to be a leading cause of maternal and fetal morbidity and mortality. The aim of this study was to investigate whether changes in oxidative status are correlated with alterations in the L-arginine-nitric oxide pathway and platelet aggregation in PE. Plasma and platelets from women with PE (n=24) or normotensive pregnancy (NP, n=27) recruited in the third trimester of gestation were used to measure oxidative damage assessed by protein carbonyl content, antioxidant activities of superoxide dismutase (SOD), catalase (CAT) and nitrite levels. Transport of L-[(3)H]-arginine, as well as the activities of the nitric oxide (NO) synthase (eNOS and inducible NO synthase (iNOS)) and platelet aggregation, were also evaluated. Plasma nitrite levels and the activities of SOD and CAT were reduced in PE (5.2±2.7, 3.4±0.8, 0.3±0.4, respectively, P<0.05) compared with NP (8.7±2.3, 6.7±3.1, 1.0±0.5, respectively), whereas protein carbonyl content and L-arginine levels were not significantly different between PE and NP groups. In platelets, L-arginine transport was reduced in PE (19.2±10.5, P<0.05) compared with NP (62.0±31.1), whereas the NOS activity, eNOS and iNOS expression, nitrite levels and platelet aggregation were unaffected. Protein carbonyl content was increased, and CAT activity was reduced in platelets from PE (0.03±0.02, 0.55±0.30, respectively, P<0.05), compared with NP (0.005±0.005, 1.01±0.36, respectively). The data suggest that a systemic impairment of antioxidant defense mechanisms is associated with decreased plasma nitrite levels, which may contribute to hypertension in PE. Oxidative stress may contribute to the reduced influx of L-arginine in platelets. Compensatory mechanisms may contribute to the maintenance of NO production and its modulatory role on platelet function.

Formação do terapeuta ocupacional para o trabalho na Atenção Primária à Saúde (APS): contribuições para o debate / Training of occupational therapists for Primary Health Care (PHC): contributions to the debate

As autoras apresentam os debates do grupo de trabalho sobre Formação do Terapeuta Ocupacional para a Atenção Primária à Saúde (APS) realizados durante o I Seminário Nacional de Terapia Ocupacional em APS, desenvolvido durante o XII Congresso Brasileiro e IX Congresso Latinoamericano de Terapia Ocupacional, em outubro de 2011 (São Paulo, SP). Também situam o campo da formação profissional para a APS no contexto do Sistema Único de Saúde (SUS) e destacam sua importância para a formação de terapeutas ocupacionais. São apresentados aspectos relevantes das Diretrizes Curriculares Nacionais específicas nas proposições de formação de profissionais para esse nível assistencial, também colocadas pela Política de Reorientação da Formação Profissional em Saúde (Pró-Saúde), bem como as experiências de formação nesse nível assistencial desenvolvidas pelas instituições de ensino de origem das autoras. Conclui-se que o ensino de graduação nesse nível assistencial possibilita contato estreito de estudantes e docentes com as demandas e necessidades de saúde, processo saúde-doença e seus determinantes em cenários mais próximos da vida cotidiana das pessoas acompanhadas e dos serviços. O ensino de Terapia Ocupacional na APS também possibilita a discussão sobre suas contribuições na promoção da saúde e prevenção de doenças, no diagnóstico precoce, tratamento e reabilitação, o que pode facilitar o acesso de populações antes não consideradas prioritárias na APS. Este seminário foi um importante momento de discussão dos desafios da vinculação da profissão ao SUS.(AU)

Herein presented are the topics debated at the research group meeting on Training of Occupational Therapists for Primary Health Care (PHC) that took place during the First National Seminar on Occupational Therapy in PHC, at the XII Brazilian Congress and IX Latin American Congress of Occupational Therapy in October 2011 in Sao Paulo, Brazil. In addition, the of vocational training for PHC is situated within the context of the Unified Health System (UHS) and its importance for the training of occupational therapists. We present relevant aspects of specific National Curriculum Guidelines suggested for the professional training at this level of care, which have also been addressed by the Reorientation of Vocational Training in Health Policy (PRO Health). Experiences gained by the authors? educational institutions when training at this level of care are also presented. It was possible to conclude that undergraduate studies at this level of care enables students and teachers to come into close contact with health demands and needs, health-disease process and its determinants, within a scenario closer to the everyday life of the people being cared and the service they receive. The teaching of Occupational Therapy (OT) at PHC further allows the debate of its contributions in promoting health and preventing disease, early diagnosis, treatment and rehabilitation, which may facilitate the access to populations previously not considered priority by the PHC. This seminar was important for discussing the challenges of linking the OT profession to the UHS.(AU)

Formação do terapeuta ocupacional para o trabalho na Atenção Primária à Saúde (APS): contribuições para o debate / Training of occupational therapists for Primary Health Care (PHC): contributions to the debate

As autoras apresentam os debates do grupo de trabalho sobre Formação do Terapeuta Ocupacional para a Atenção Primária à Saúde (APS) realizados durante o I Seminário Nacional de Terapia Ocupacional em APS, desenvolvido durante o XII Congresso Brasileiro e IX Congresso Latinoamericano de Terapia Ocupacional, em outubro de 2011 (São Paulo, SP). Também situam o campo da formação profissional para a APS no contexto do Sistema Único de Saúde (SUS) e destacam sua importância para a formação de terapeutas ocupacionais. São apresentados aspectos relevantes das Diretrizes Curriculares Nacionais específicas nas proposições de formação de profissionais para esse nível assistencial, também colocadas pela Política de Reorientação da Formação Profissional em Saúde (Pró-Saúde), bem como as experiências de formação nesse nível assistencial desenvolvidas pelas instituições de ensino de origem das autoras. Conclui-se que o ensino de graduação nesse nível assistencial possibilita contato estreito de estudantes e docentes com as demandas e necessidades de saúde, processo saúde-doença e seus determinantes em cenários mais próximos da vida cotidiana das pessoas acompanhadas e dos serviços. O ensino de Terapia Ocupacional na APS também possibilita a discussão sobre suas contribuições na promoção da saúde e prevenção de doenças, no diagnóstico precoce, tratamento e reabilitação, o que pode facilitar o acesso de populações antes não consideradas prioritárias na APS. Este seminário foi um importante momento de discussão dos desafios da vinculação da profissão ao SUS.

Herein presented are the topics debated at the research group meeting on Training of Occupational Therapists for Primary Health Care (PHC) that took place during the First National Seminar on Occupational Therapy in PHC, at the XII Brazilian Congress and IX Latin American Congress of Occupational Therapy in October 2011 in Sao Paulo, Brazil. In addition, the of vocational training for PHC is situated within the context of the Unified Health System (UHS) and its importance for the training of occupational therapists. We present relevant aspects of specific National Curriculum Guidelines suggested for the professional training at this level of care, which have also been addressed by the Reorientation of Vocational Training in Health Policy (PRO Health). Experiences gained by the authors? educational institutions when training at this level of care are also presented. It was possible to conclude that undergraduate studies at this level of care enables students and teachers to come into close contact with health demands and needs, health-disease process and its determinants, within a scenario closer to the everyday life of the people being cared and the service they receive. The teaching of Occupational Therapy (OT) at PHC further allows the debate of its contributions in promoting health and preventing disease, early diagnosis, treatment and rehabilitation, which may facilitate the access to populations previously not considered priority by the PHC. This seminar was important for discussing the challenges of linking the OT profession to the UHS.

Pessoas com deficiência: entre necessidades e atenção à saúde / People with disabilities: between needs and health care

Este estudo traça o perfi l das pessoas com deficiência e suas necessidades de saúde em um bairro da cidade de Salvador, Bahia. Neste, buscou-se conhecer a situação de vida e saúde das pessoas com deficiência a partir do contexto onde vivem. A investigação foi realizada em duas áreas de cobertura do Programa de Agentes Comunitários de Saúde nas quais foram aplicados questionários abertos com pessoas com deficiência física e sensorial. Foram selecionadas variáveis sócio-demográficas, bem como acesso a serviços e projetos de vidafuturos. Os resultados revelam uma população em que predominam adultos e idosos, negros, do sexo feminino, com renda média entre meio e três salários mínimos, baixa escolaridade e com difi culdades em relação ao acesso a serviços de saúde no bairro e na cidade. As pessoas referem necessidade de atendimento especializado de saúde no bairro, melhorias nas condições de vida e expressam o desejo no que tange ao retorno de atividades que realizavam antes da deficiência. Tais dados evidenciam uma população caracterizada por um complexo multifacetado de exclusão e privação coletiva e apontam para a necessidade de compreensão dos processos sociais na melhoria da assistência oferecidas às populações. Para isso, aponta-se a reabilitação na Atenção Primária à Saúde como estratégia de relevância para mudanças na atenção à saúde das pessoas com deficiência

This study traces the profile of people with disabilities, as well as their health needs, in a neighborhood of Salvador, State of Bahia. In this, the life and health conditions of people with disabilities in the context they live were studied. The research was carried out in two coverage areas of the Community Health Workers Program (?Programa de Agentes Comunitários de Saúde?), where open-ended questionnaires were conducted with people with physical and sensory disabilities. Socio-demographic variables on disability and access to services and projects for future life were selected. Results showed that the population is comprised predominantly of adults and elderly, African descent, female, with average income between half and three minimum wages, poorly educated, presenting difficulties in relation to access to health services in the neighborhood and the city. People with disabilities refer to the need of specialized health care in the neighborhood, improvements in life conditions, and expressed the desire to resume the activities they used to perform before the disability. These data reveal a population characterized by a multifaceted complex of collective exclusion and deprivation and point to the need for understanding social processes when improving the assistance offered to the population. To this end, it is necessary to rehabilitate the Primary Health Care as a strategy of relevance to changes in health care for people with disabilities

[Ca2+ and sphingolipids as modulators for apoptosis and cancer]. / El Ca2+ y los esfingolipidos como moduladores de la apoptosis y el cáncer.

Ca2+ is a second messenger which regulates many functions directly related with cancer such as proliferation, differentiation and apoptosis. The intracellular Ca2+ concentration ([Ca2+],) is finely regulated by several mechanisms, among them ionic channels, the endoplasmic reticulum Ca2+-ATPase (SERCA), the plasma membrane calcium pump (PMCA) and the mitochondrial Ca2+ transport. In cancer, the tumour cell proliferates without control since the capacity to recognize apoptotic signals has been lost. The apoptosis is regulated by changes in several proteins, as caspases and the Bcl-2 family members, among others. Additionally, the "reticulum stress", promoted by the accumulation and aggregation of unfolded proteins in the interior of the endoplasmic reticulum (ER), ussually leads to apoptosis. The "reticulum stress" can be induced by several agents, remarkably with thapsigargin, a selective inhibitor of the SERCA, which in turn induces a large increment in [Ca2+],, leading to apoptosis. As a consequence, currently, derivatives of thapsigargin are successfully been assayed as anti-neoplastic agents. Ca2+ is then transferred to the mitochondria, where it is known to constitute a main apoptotic signal. On the other hand, several sphingolipids, such as ceramide and sphingosine, and their phosphorylated derivatives ceramide-1-phosphate and sphingosine-1-phosphate, directly involved in the [Ca2+]1 regulation, are also recognized as signal messengers related with cancer processes. In this review we discuss new evidences on the effect of several sphingolipids in the intracellular Ca2+ homeostasis and its relationship with apoptosis and cancer.

El Ca2+ y los esfingolípidos como moduladores de la apoptosis y el cáncer / Ca2+ and sphingolipids as modulators for apoptosis and cancer

El Ca2+ es un segundo mensajero que regula funciones directamente relacionadas con el cáncer como la proliferación, diferenciación y la apoptosis. La concentración intracelular de Ca2+ ([Ca2+]i) está altamente regulada por diversos mecanismos entre los que destacan canales iónicos, la Ca2+-ATPasa del retículo endoplasmático (SERCA) y de la membrana plasmática (PMCA), y el transporte de Ca2+ mitocondrial. En el cáncer, la célula tumoral prolifera sin control tras su incapacidad de reconocer señales apoptóticas. La apoptosis es mediada a través de cambios en la actividad de ciertas proteínas como las caspasas y miembros de la familia Bcl-2. Adicionalmente, el “estrés del retículo”, promovido por la acumulación y agregación de proteínas mal plegadas en el interior del retículo endoplasmático (RE), puede desencadenar la apoptosis. El “estrés del retículo” es inducido por una variedad de agentes, entre los que destaca la tapsigargina, inhibidor específico de la SERCA, la cual promueve un notable aumento en la [Ca2+]i, induciendo además apoptosis. En consecuencia, actualmente se están ensayando exitosamente derivados de la tapsigargina como agentes antineoplásicos. El Ca2+ es transferido a la mitocondria desencadenando señales apoptóticas. Por otra parte, los esfingolípidos, como la ceramida y la esfingosina, y sus derivados fosforilados, la ceramida-1-fosfato y la esfingosina-1-fosfato, los cuales regulan la [Ca2+]i, también están estrechamente vinculados con la señalización intracelular en procesos relacionados con el cáncer. Esta revisión discute nuevas evidencias sobre el efecto de estos esfingolípidos en la homeostasis de Ca+2 intracelular y su conexión con la apoptosis y el cáncer.

Ca2+ is a second messenger which regulates many functions directly related with cancer such as proliferation, differentiation and apoptosis. The intracellular Ca2+ concentration ([Ca2+]i) is finely regulated by several mechanisms, among them ionic channels, the endoplasmic reticulum Ca2+-ATPase (SERCA), the plasma membrane calcium pump (PMCA) and the mitochondrial Ca2+ transport. In cancer, the tumour cell proliferates without control since the capacity to recognize apoptotic signals has been lost. The apoptosis is regulated by changes in several proteins, as caspases and the Bcl-2 family members, among others. Additionally, the “reticulum stress”, promoted by the accumulation and aggregation of unfolded proteins in the interior of the endoplasmic reticulum (ER), ussually leads to apoptosis. The “reticulum stress” can be induced by several agents, remarkably with thapsigargin, a selective inhibitor of the SERCA, which in turn induces a large increment in [Ca2+]I, leading to apoptosis. As a consequence, currently, derivatives of thapsigargin are successfully been assayed as anti-neoplastic agents. Ca2+ is then transferred to the mitochondria, where it is known to constitute a main apoptotic signal. On the other hand, several sphingolipids, such as ceramide and sphingosine, and their phosphorylated derivatives ceramide-1-phosphate and sphingosine-1-phosphate, directly involved in the [Ca2+]I regulation, are also recognized as signal messengers related with cancer processes. In this review we discuss new evidences on the effect of several sphingolipids in the intracellular Ca2+ homeostasis and its relationship with apoptosis and cancer.

The marine sponge toxin agelasine B increases the intracellular Ca(2+) concentration and induces apoptosis in human breast cancer cells (MCF-7).

PURPOSE: In search for new drugs derived from natural products for the possible treatment of cancer, we studied the action of agelasine B, a compound purified from a marine sponge Agelas clathrodes. METHODS: Agelasine B was purified from a marine sponge Agelas clathrodes and assayed for cytotoxicity by MTT on two human breast cancer cells (MCF-7 and SKBr3), on a prostate cancer cells (PC-3) and on human fibroblasts. Changes in the intracellular Ca(2+) concentrations were assessed with FURA 2 and by confocal microscopy. Determination of Ca(2+)-ATPase activity was followed by Pi measurements. Changes in the mitochondria electrochemical potential was followed with Rhodamine 123. Apoptosis and DNA fragmentation were determined by TUNEL experiments. RESULTS: Upon agelasine B treatment, cell viability of both human breast cancer cell lines was one order of magnitude lower as compared with fibroblasts (IC(50) for MCF-7 = 2.99 µM; SKBr3: IC(50) = 3.22 µM vs. fibroblasts: IC(50) = 32.91 µM), while the IC(50) for PC-3 IC(50) = 6.86 µM. Agelasine B induced a large increase in the intracellular Ca(2+) concentration in MCF-7, SKBr3, and PC-3 cells. By the use of confocal microscopy coupled to a perfusion system, we could observe that this toxin releases Ca(2+) from the endoplasmic reticulum (ER). We also demonstrated that agelasine B produces a potent inhibition of the ER Ca(2+)-ATPase (SERCA), and that this compound induced the fragmentation of DNA. Accordingly, agelasine B reduced the expression of the anti-apoptotic protein Bcl-2 and was able to activate caspase 8, without affecting the activity of caspase 7. CONCLUSIONS: Agelasine B in MCF-7 cells induce the activation of apoptosis in response to a sustained increase in the [Ca(2+)]( i ) after blocking the SERCA activity. The reproduction of the effects of agelasine B on cell viability and on the [Ca(2+)]( I ) obtained on SKBr3 and PC-3 cancer cells strongly suggests the generality of the mechanism of action of this toxin.

Pessoas com deficiência: entre necessidades e atenção à saúde / People with disabilities: between needs and health care

Este estudo traça o perfi l das pessoas com deficiência e suas necessidades de saúde em um bairro da cidade de Salvador, Bahia. Neste, buscou-se conhecer a situação de vida e saúde das pessoas com deficiência a partir do contexto onde vivem. A investigação foi realizada em duas áreas de cobertura do Programa de Agentes Comunitários de Saúde nas quais foram aplicados questionários abertos com pessoas com deficiência física e sensorial. Foram selecionadas variáveis sócio-demográficas, bem como acesso a serviços e projetos de vidafuturos. Os resultados revelam uma população em que predominam adultos e idosos, negros, do sexo feminino, com renda média entre meio e três salários mínimos, baixa escolaridade e com difi culdades em relação ao acesso a serviços de saúde no bairro e na cidade. As pessoas referem necessidade de atendimento especializado de saúde no bairro, melhorias nas condições de vida e expressam o desejo no que tange ao retorno de atividades que realizavam antes da deficiência. Tais dados evidenciam uma população caracterizada por um complexo multifacetado de exclusão e privação coletiva e apontam para a necessidade de compreensão dos processos sociais na melhoria da assistência oferecidas às populações. Para isso, aponta-se a reabilitação na Atenção Primária à Saúde como estratégia de relevância para mudanças na atenção à saúde das pessoas com deficiência.(AU)

This study traces the profile of people with disabilities, as well as their health needs, in a neighborhood of Salvador, State of Bahia. In this, the life and health conditions of people with disabilities in the context they live were studied. The research was carried out in two coverage areas of the Community Health Workers Program (?Programa de Agentes Comunitários de Saúde?), where open-ended questionnaires were conducted with people with physical and sensory disabilities. Socio-demographic variables on disability and access to services and projects for future life were selected. Results showed that the population is comprised predominantly of adults and elderly, African descent, female, with average income between half and three minimum wages, poorly educated, presenting difficulties in relation to access to health services in the neighborhood and the city. People with disabilities refer to the need of specialized health care in the neighborhood, improvements in life conditions, and expressed the desire to resume the activities they used to perform before the disability. These data reveal a population characterized by a multifaceted complex of collective exclusion and deprivation and point to the need for understanding social processes when improving the assistance offered to the population. To this end, it is necessary to rehabilitate the Primary Health Care as a strategy of relevance to changes in health care for people with disabilities.(AU)

Efecto de esfingolípidos y Agelosina B en la movilización de Ca2+ y la señalización celular en células de cáncer de mama (MCF-7) y su relación con la apoptosis / Effect of sphingolipids and Agelosin B on Ca2 + mobilization and cell signaling in breast cancer cells (MCF-7) and its relationship with apoptosis

Los esfingolípidos, como la ceramida (Cer), la ceramida-1-fosfato (C-1-P), la esfingosina (Sph) y la esfingosina-1-fosfato (S-1P) estan relacionados con la señalización intracelular en procesos como crecimiento celular, movilización intracelular de Ca+2 y apoptósis. En este trabajo se evaluó el efecto de estos esfingolípidos en la homeostasis de Ca+2 intracelular y en la apoptósis en células de cáncer de mama MCF-7. Se utilizaron fluoróforos específicos para el Ca+2 y microscopía confocal. Se demostró que en estas células, la Sph (20 uM), la Cer (10uM), la S-P (2uM) y la C--P (uM) aumentaron la concentración intracelular ce Ca+2, induciendo su liberación desde el retículo endoplasmático (RE). Además, se observo que la esfingosina abrioun canal de Ca2+ en la membrana plasmática. También se demostró que la Cer inhibe parcialmente la actividad de la Ca2+-ATPasa del RE (SERCA), de forma dosis dependiente, mientras que la ceramina, su análogo no hidrolisable la inhibe totalmente. La Sph también inhibe completamente la actividad de la SERCA, a la misma concentración que induce la liberación del Ca+2 del RE. Asimismo, se evaluó el efecto de estos esfingolípidos sobre la inducción de la apotósis en células MCF-7 evidenciando que el tratamiento con la Cer, la ceramida, la Sph inducen toxicidad. También se observo que mientras la ceramida activo la caspasa 7 y la caspasa 8, el esfingolipido natural, la Cer no tuvo ningún efecto. Por su parte, la Sph activa la caspasa 8 sin modificar la activdad de la caspasa 7. Tanto la Cer, como la ceramida y la Sph, disminuyeron la expresión de la proteína Bcl-2 amti-apoptótica, y también indujeron la fragmentación de ADN, visualizada mediante la técnica de TUNEL, demostrando que estos esfingolípidos inducen apoptósis en MCF-7. La agelasina B, toxina purificada a partir de la esponja marina Agelas clathrodes tiene un efecto citotóxico un orden de magnitud mayor en MCF-7, en comparación con fibroplastos humanos. La agelasina B induce la liberación del Ca+2 almacenado en el RE en celulas MCF-7, ademas de inhibir la actividad de la SERCA en un 100%. También se demostró que esta toxina induce apoptosis, ya que disminuye el potencial de membrana mitocondrial, activa la caspasa 8, disminuye la expresion de la proteina Bcl-2 e induce fragmentación del ADN de las células MCF-7. Este mecanismo es similar al efecto de la tapsigargina.