ASP-2/Trans-sialidase chimeric protein induces robust protective immunity in experimental models of Chagas' disease.

Immunization with the Amastigote Surface Protein-2 (ASP-2) and Trans-sialidase (TS) antigens either in the form of recombinant protein, encoded in plasmids or human adenovirus 5 (hAd5) confers robust protection against various lineages of Trypanosoma cruzi. Herein we generated a chimeric protein containing the most immunogenic regions for T and B cells from TS and ASP-2 (TRASP) and evaluated its immunogenicity in comparison with our standard protocol of heterologous prime-boost using plasmids and hAd5. Mice immunized with TRASP protein associated to Poly-ICLC (Hiltonol) were highly resistant to challenge with T. cruzi, showing a large decrease in tissue parasitism, parasitemia and no lethality. This protection lasted for at least 3 months after the last boost of immunization, being equivalent to the protection induced by DNA/hAd5 protocol. TRASP induced high levels of T. cruzi-specific antibodies and IFNγ-producing T cells and protection was primarily mediated by CD8+ T cells and IFN-γ. We also evaluated the toxicity, immunogenicity, and efficacy of TRASP and DNA/hAd5 formulations in dogs. Mild collateral effects were detected at the site of vaccine inoculation. While the chimeric protein associated with Poly-ICLC induced high levels of antibodies and CD4+ T cell responses, the DNA/hAd5 induced no antibodies, but a strong CD8+ T cell response. Immunization with either vaccine protected dogs against challenge with T. cruzi. Despite the similar efficacy, we conclude that moving ahead with TRASP together with Hiltonol is advantageous over the DNA/hAd5 vaccine due to pre-existing immunity to the adenovirus vector, as well as the cost-benefit for development and large-scale production.

Comparative transcriptome analysis of endothelial progenitor cells of HbSS patients with and without proliferative retinopathy.

Among sickle cell anemia (SCA) complications, proliferative sickle cell retinopathy (PSCR) is one of the most important, being responsible for visual impairment in 10-20% of affected eyes. The aim of this study was to identify differentially expressed genes (DEGs) present in pathways that may be implicated in the pathophysiology of PSCR from the transcriptome profile analysis of endothelial progenitor cells. RNA-Seq was used to compare gene expression profile of circulating endothelial colony-forming cells (ECFCs) from HbSS patients with and without PSCR. Furthermore, functional enrichment analysis and protein-protein interaction (PPI) networks were performed to gain further insights into biological functions. The differential expression analysis identified 501 DEGs, when comparing the groups with and without PSCR. Furthermore, functional enrichment analysis showed associations of the DEGs in 200 biological processes. Among these, regulation of mitogen-activated protein (MAP) kinase activity, positive regulation of phosphatidylinositol 3-kinase (PI3K), and positive regulation of Signal Transducer and Activator of Transcription (STAT) receptor signaling pathway were observed. These pathways are associated with angiogenesis, cell migration, adhesion, differentiation, and proliferation, important processes involved in PSCR pathophysiology. Moreover, our results showed an over-expression of VEGFC (vascular endothelial growth factor-C) and FLT1 (Fms-Related Receptor Tyrosine Kinase 1) genes, when comparing HbSS patients with and without PSCR. These results may indicate a possible association between VEGFC and FLT1 receptor, which may activate signaling pathways such as PI3K/AKT and MAPK/ERK and contribute to the mechanisms implicated in neovascularization. Thus, our findings contain preliminary results that may guide future studies in the field, since the molecular mechanisms of PSCR are still poorly understood.

Autoregulatory control of microtubule binding in doublecortin-like kinase 1.

The microtubule-associated protein, doublecortin-like kinase 1 (DCLK1), is highly expressed in a range of cancers and is a prominent therapeutic target for kinase inhibitors. The physiological roles of DCLK1 kinase activity and how it is regulated remain elusive. Here, we analyze the role of mammalian DCLK1 kinase activity in regulating microtubule binding. We found that DCLK1 autophosphorylates a residue within its C-terminal tail to restrict its kinase activity and prevent aberrant hyperphosphorylation within its microtubule-binding domain. Removal of the C-terminal tail or mutation of this residue causes an increase in phosphorylation within the doublecortin domains, which abolishes microtubule binding. Therefore, autophosphorylation at specific sites within DCLK1 has diametric effects on the molecule's association with microtubules. Our results suggest a mechanism by which DCLK1 modulates its kinase activity to tune its microtubule-binding affinity. These results provide molecular insights for future therapeutic efforts related to DCLK1's role in cancer development and progression.

In vitro and in vivo anti-inflammatory activity and chemical composition of Renealmia petasites Gagnep.

The study aimed to investigate the chemical composition and the anti-inflammatory activity of the hydroethanolic rhizomes, stems, and leaf extracts of Renealmia petasites using in vitro and in vivo assays. The chemical composition of the extracts was characterized in a linear iron trap mass spectrometer. Total phenolic, flavonoid, and tannin content were determined by spectrophotometry analyses. In vitro anti-inflammatory activity was investigated in lipopolysaccharide-stimulated macrophages evaluating the influence on the production of superoxide anion (O2-), nitric oxide (NO), and the pro-inflammatory cytokines tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). In vivo effects were determined using the air pouch model in which were inoculated carrageenan and thereafter treated with 50 mg/kg of the hydroethanolic extracts of R. petasites. After 4 and 24 h, the cellular influx, protein exudation, cytokines, and nitric oxide were evaluated. Eight compounds were tentatively identified in the R. petasites extracts, suggesting five diarylheptanoids, one flavonoid, and two fatty alcohols. The in vitro results showed that the extracts were capable of blocking free radicals and/or inhibiting their intracellular actions by inhibiting the production of important mediators of the inflammatory process, such as NO, O2-, TNF-α, and IL-6. In vivo, R. petasites significantly decrease the influx of leukocytes, mainly neutrophils, protein exudation, NO, TNF-α, and IL-6 concentration in the air pouch model. The results evidenced that R. petasites can be considered a promising alternative therapy for the treatment and management of osteoarthritis and other inflammatory diseases.

Mishel's Model of Uncertainty Describing Categories and Subcategories in Fibromyalgia Patients, a Scoping Review.

The aim of this review was to demonstrate the presence of categories and subcategories of Mishel's model in the experiences of patients with fibromyalgia by reviewing qualitative studies. Uncertainty is defined as the inability to determine the meaning of disease-related events. A scoping review of qualitative studies was carried out. Twenty articles were included, with sample sizes ranging from 3 to 58 patients. Articles from different countries and continents were included. Three categories of the model and eight subcategories could be shown to be present in the experiences of fibromyalgia patients through the scoping review. The first category, concerning antecedents of uncertainty in patients with fibromyalgia, is constituted by the difficulty in coping with symptoms, uncertainty about the diagnosis and uncertainty about the complexity of the treatment. The second concerns the cognitive process of anxiety, stress, emotional disorder and social stigma. The third category refers to coping with the disease, through the management of social and family support and the relationship with health care professionals.

Aplicaciones de la hormona de crecimiento humana recombinante en HIV. Efectos sobre el aparato inmune / Aplication of the recombinant human growth hormone in HIV. Effects on the immune system

El presente trabajo realiza una investigación bibliográfica sobre el uso clínico de RhGH en pacientes adultos HIV en su rol inmunomodulador mediante búsqueda booleana en Pubmed de los términos RhGH yHIV en artículos de ensayos clínicos, únicamente en adultos a partir de los 19 o más años de edad hasta enero del 2019

Notificações de óbitos por causas externas e violência contra idosos: uma realidade velada / Reporting of deaths from external causes and violence against older people: a veiled reality

Objetivo: Descrever o perfil da morbimortalidade da violência contra a pessoa idosa. Métodos: Trata-se de um estudo descritivo e retrospectivo de 14.900 notificações extraídas do Sistema de Informação de Agravos de Notificação (SINAN) e de 18.228 casos do Sistema de Informação de Mortalidade (SIM), de 2012 a 2017, do estado de Minas Gerais, Brasil. Analisaram-se as notificações de violência segundo características das vítimas (sexo, faixa etária, raça/cor e escolaridade), da ocorrência (local, tipo de violência, características do agressor) e as variáveis referentes ao óbito (sexo, faixa etária, raça/cor, estado civil, local de ocorrência e causa do óbito). Resultados: Das notificações analisadas, 54,5% (8.116) das vítimas eram mulheres, 42,8% (6.384) brancos e 47,6% (7.082) com ensino fundamental incompleto/analfabeto. A violência física deu-se em 69,5% (10.356) dos casos, e o filho apresenta maior frequência no perfil de agressor, com 26,4% (3.928). Em relação aos óbitos por causas externas, 60,9% (11.096) eram homens, 37,4% (6.815) com mais de 80 anos, 54,9% (10.011) brancos e 37,7% (6.867) casados. O hospital é o local de óbito mais relatado, 64% (11.664). Óbitos por outras causas externas: 42,5% (7.741), sendo as quedas 32,4% (5.897) do total. Conclusão: As principais vítimas são as mulheres idosas, com baixa escolaridade, e de violência física perpetrada, principalmente, pelo filho, porém aqueles que vêm a óbito com mais frequência são os homens idosos, tendo como principal causa as quedas e os acidentes de transporte. (AU)

The emergence of pathogenic TNF/iNOS producing dendritic cells (Tip-DCs) in a malaria model of acute respiratory distress syndrome (ARDS) is dependent on CCR4.

Malaria-associated acute respiratory distress syndrome (MA-ARDS) and acute lung injury (ALI) are complications that cause lung damage and often leads to death. The MA-ARDS/ALI is associated with a Type 1 inflammatory response mediated by T lymphocytes and IFN-γ. Here, we used the Plasmodium berghei NK65 (PbN)-induced MA-ALI/ARDS model that resembles human disease and confirmed that lung CD4+ and CD8+ T cells predominantly expressed Tbet and IFN-γ. Surprisingly, we found that development of MA-ALI/ARDS was dependent on functional CCR4, known to mediate the recruitment of Th2 lymphocytes and regulatory T cells. However, in this Type 1 inflammation-ARDS model, CCR4 was not involved in the recruitment of T lymphocytes, but was required for the emergence of TNF-α/iNOS producing dendritic cells (Tip-DCs) in the lungs. In contrast, recruitment of Tip-DCs and development of MA-ALI/ARDS were not altered in CCR2-/- mice. Importantly, we showed that NOS2-/- mice are resistant to PbN-induced lung damage, indicating that reactive nitrogen species produced by Tip-DCs play an essential role in inducing MA-ARDS/ALI. Lastly, our experiments suggest that production of IFN-γ primarily by CD8+ T cells is required for inducing Tip-DCs differentiation in the lungs and the development of MA-ALI/ARDS model.

Adverse events of vaccines and the consequences of non-vaccination: a critical review.

OBJECTIVE: To analyze the risks related to vaccines and the impacts of non-vaccination on the world population. METHODS: This is a narrative review that has considered information present in the bibliographic databases NCBI-PubMed, Medline, Lilacs, and Scientific Electronic Library Online (SciELO), between November 2015 and November 2016. For the analysis of outbreaks caused by non-vaccination, we considered the work published between 2010 and 2016. RESULTS: We have described the main components of the vaccines offered by the Brazilian public health system and the adverse events associated with these elements. Except for local inflammatory reactions and rare events, such as exacerbation of autoimmune diseases and allergies, no causal relationship has been demonstrated between the administration of vaccines and autism, Alzheimer's disease, or narcolepsy. On the other hand, the lack of information and the dissemination of non-scientific information have contributed to the reemergence of infectious diseases in several countries in the world and they jeopardize global plans for the eradication of these diseases. CONCLUSIONS: The population should be well informed about the benefits of vaccination and health professionals should assume the role of disseminating truthful information with scientific support on the subject, as an ethical and professional commitment to society.

Prevalence and Risk Factors of self-reported dry eye in Brazil using a short symptom questionnaire.

To evaluate dry eye prevalence and investigate associated risk factors in Brazil by applying a short questionnaire of symptoms and risk factors. A cross-sectional study of 3,107 participants from all the five different geopolitical regions of Brazil. Overall prevalence of dry eye in this study population was 12.8%. Dry eye previous diagnosis was reported by 10.2% and presence of severe symptoms in 4.9%. Logistic regression analysis confirmed some significantly risk factors, such as female sex (Odds Ratio (OR) 1.74; 95% Confidence Interval (CI): 1.12-1.93), age ≥60 year-old (OR 2.00; 95%CI: 1.44-2.77), history of ocular surgery (OR 1.84; 95%CI: 1.30-2.60), contact lens wear (OR 1.93; 95%CI: 1.36-2.73), cancer treatment (OR 3.03; 95%CI: 1.36-6.59), computer use >6 hours per day (OR 1.77; 95%CI: 1.36-2.31), antidepressants (OR 1.61; 95%CI: 1.12-2.31) and anti-allergy (OR 2.11; 95%CI: 1.54-2.89) medications. Nevertheless, when stratified by regions, each one had its own significant factors and inherent characteristics. This is the first study about prevalence and risk factors of dry eye in a large population sample from all regions of Brazil. Dry eye is a common condition in the Brazilian population and prevalence rates varies substantially in the different geographic regions of the country, possibly reflecting climate and socioeconomic discrepancies.

Adverse events of vaccines and the consequences of non-vaccination: a critical review / Eventos adversos de vacinas e as consequências da não vacinação: uma análise crítica

ABSTRACT OBJECTIVE: To analyze the risks related to vaccines and the impacts of non-vaccination on the world population. METHODS: This is a narrative review that has considered information present in the bibliographic databases NCBI-PubMed, Medline, Lilacs, and Scientific Electronic Library Online (SciELO), between November 2015 and November 2016. For the analysis of outbreaks caused by non-vaccination, we considered the work published between 2010 and 2016. RESULTS: We have described the main components of the vaccines offered by the Brazilian public health system and the adverse events associated with these elements. Except for local inflammatory reactions and rare events, such as exacerbation of autoimmune diseases and allergies, no causal relationship has been demonstrated between the administration of vaccines and autism, Alzheimer's disease, or narcolepsy. On the other hand, the lack of information and the dissemination of non-scientific information have contributed to the reemergence of infectious diseases in several countries in the world and they jeopardize global plans for the eradication of these diseases. CONCLUSIONS: The population should be well informed about the benefits of vaccination and health professionals should assume the role of disseminating truthful information with scientific support on the subject, as an ethical and professional commitment to society.

RESUMO OBJETIVO: Analisar os riscos relacionados às vacinas e os impactos da não vacinação para a população mundial. MÉTODOS: Revisão narrativa que considerou informações contidas nas bases de dados bibliográficos NCBI-PubMed, Medline, Lilacs e Scientific Electronic Library Online (SciELO), no período compreendido entre novembro de 2015 e novembro de 2016. Para a análise de surtos ocasionados pela não vacinação foram considerados os trabalhos publicados entre 2010 e 2016. RESULTADOS: Foram descritos os principais componentes das vacinas oferecidas pelo sistema público de saúde brasileiro e eventos adversos associados a esses elementos. Com exceção de reações inflamatórias locais e efeitos raros como exacerbação de doenças autoimunes e alergias, não foi demonstrada relação causal entre a administração de vacinas e autismo, mal de Alzheimer ou narcolepsia. Por outro lado, a falta de informações e a divulgação de informações não científicas têm contribuído para a reemergência de doenças infecciosas em diversos países no mundo e põe em risco planos globais para a erradicação de doenças infecciosas. CONCLUSÕES: A população deve estar bem informada quanto aos benefícios da vacinação e os profissionais da saúde devem assumir o papel de divulgar informações verídicas e com respaldo científico sobre o tema, como compromisso ético e profissional junto à sociedade.

Prevalência de escoliose em escolares do ensino fundamental público / Prevalence of scoliosis in public elementary school students

RESUMO Objetivo: Avaliar a prevalência de escoliose e os fatores de risco em alunos do ensino fundamental. Métodos: Estudo transversal realizado em 954 alunos em 2015. O instrumento envolvido foi um questionário sobre hábitos posturais, condições socioeconômicas e fatores demográficos. As medidas antropométricas, incluindo altura e peso, a inspeção visual da deformidade da coluna vertebral, o nivelamento dos ombros e o Teste de Adams foram obtidos. A amostra foi calculada na frequência esperada de 12,3%, erro aceitável de 2,0% e nível de confiança de 95,0%. Para comparar as proporções, o teste do qui-quadrado ou o teste exato de Fisher foram aplicados. A associação entre escoliose e fatores de risco foi avaliada por regressão logística, sendo significante p<0,05. Resultados: A prevalência de escoliose foi de 24,3%, superior em obesos e estudantes que adotavam posição sentada durante um longo período de tempo. Estudantes obesos mostraram risco 1,8 vez superior no Teste de Adams positivo quando comparados aos eutróficos/magros e risco 2,1 vezes superior comparados aos alunos com sobrepeso. A posição sentada para assistir à televisão aumenta a chance de Teste de Adams positivo em 38,0% quando comparada à posição deitada. A obesidade aumenta o risco de Teste de Adams positivo em 74,0 e 98,0% quando comparada, respectivamente, à magreza/eutrofia e ao sobrepeso. Conclusões: Houve elevada prevalência de escoliose em estudantes de escolas públicas do ensino fundamental em Santos. Os fatores que mais influenciaram esse desvio de coluna foram a obesidade e a posição adotada pelos alunos para assistir à televisão.

ABSTRACT Objective: To evaluate the prevalence of scoliosis and the risk factors in elementary school students. Methods: A cross-sectional study was carried out in 954 students in 2015. The instrument involved was a questionnaire on postural habits, socioeconomic conditions, and demographic factors. The anthropometric measurements, including height and weight, a visual inspection of the deformity of the vertebral column, the leveling of shoulders, and the Adam's test were obtained. The sample was calculated in the expected frequency of 12.3%, acceptable error rate of 2.0% and confidence level of 95.0%. To compare the proportions, the chi-square test or Fisher's exact test was applied. The association between scoliosis and risk factors was evaluated by logistic regression, being significant p <0.05. Results: The prevalence of scoliosis was 24.3%, higher in obese patients and students who adopted a sitting position for a long period of time. Obese students showed a 1.8 times higher chance of testing positive Adam's Forward Bend Test when compared to normal-weight/lean and 2.1 times higher chance compared to overweight students. The sitting position for watching television increases the chance of testing positive Adam's test in 38.0%, when compared to the lying position. Obesity increases the risk of testing positive Adam's test in 74.0 and 98.0%, when compared, respectively, to the underweight/normal weight and overweight. Conclusions: There was a high prevalence of scoliosis in students from public elementary schools in Santos. The most influential factors for this deviation of the spine were obesity and the position adopted by students to watch television.

Translation and validation of the Portuguese version of a dry eye disease symptom questionnaire / Tradução e validação da versão em português de um questionário para sintomas de olho seco

ABSTRACT Purposes: A symptom questionnaire is an important tool used to quantify and qualify the impact of a disease on a patient's related quality of life and to estimate the prevalence of a certain condition within a population. Ophthalmologists frequently encounter patients with dry eye disease (DED), and therefore, evaluating the symptoms reported by these patients influences diagnosis, therapeutic monitoring, and evaluations of disease progression. The latest consensus on dry eye (Dry Eye Workshop, DEWS), published in 2007, led to the standardization of several questionnaires and a better understanding of the prevalence, severity, and overall effect of DED on the patient's quality of life. Methods: In this study, we translated into Portuguese a symptom questionnaire from DEWS that has already been used in several other population-based studies. For subsequent validation, the translated questionnaire was applied by two independent observers to a population of 30 subjects, and the results were compared in a concordance analysis. Results: The processes of translating to Portuguese and back translating the dry eye symptom questionnaire were conducted without difficulty. The high-correlation coefficients obtained when comparing the results of the initial application and the re-administration of this questionnaire to a sample of 30 individuals indicated excellent concordance with regard to results, repeatability, and reliability. Conclusions: This translated and validated questionnaire can be applied to a larger population with the intent to determine the prevalence of DED symptoms in the overall Brazilian population, as well as in distinct regions of the country.

RESUMO Objetivos: A aplicação de questionários sobre os sintomas é uma forma de quantificar e qualificar o impacto de uma determinada doença na qualidade de vida dos pacientes portadores e ainda de estimar a prevalência de uma determinada condição na população estudada. O olho seco é uma condição ocular muito prevalente na prática oftalmológica e a avaliação dos sintomas reportados pelos pacientes é uma importante ferramenta propedêutica e de acompanhamento terapêutico e evolução da doença. De acordo com o último consenso sobre olho seco (Dry Eye Worshop, DEWS) publicado em 2007, diversos questionários foram padronizados e tem sido utilizados para o melhor entendimento sobre a prevalência, gravidade e impacto na qualidade de vida dos pacientes. Métodos: Foi realizada a tradução para o português de um dos questionários de sintomas reportado no DEWS, seguido de sua validação. Trata-se de um questionário de sintomas de olho seco já utilizado em diversos outros estudos populacionais. O questionário traduzido foi aplicado em uma população de 30 indivíduos por dois observadores diferentes e os resultados foram comparados para verificação de concordância. Resultados: O processo de tradução e contra tradução do questionário de sintomas de olho seco para a língua portuguesa foi realizada sem dificuldades. A análise dos resultados obtidos na aplicação teste e re-teste do questionário em uma amostra de 30 indivíduos apresentou coeficientes de correlação altos demonstrando excelente concordância de resultados, reprodutibilidade e confiabilidade. Conclusões: A tradução e validação deste questionário permitirá sua aplicação em estudos de prevalência dos sintomas de olho seco na população brasileira, bem como comparação em diversas regiões do país.

Hacia un cuerpo de la experiencia en la educación corporal / Into a body of experience in corporal education / Por um corpo da experiência na educação corporal

Se trata de pensar la experiencia, esta vez desde un cuerpo inmanente, singular y encarnado. Iniciamos con algunas tensiones ejercidas por filósofos, antropólogos y sociólogos sobre el paradigma cartesiano, para, posteriormente, proponer algunas de sus posibilidades en la Educación Corporal. Interesa, aquí, ir más allá del cuerpo disecado y categorizado, para dirigirse a un cuerpo de la experiencia, es decir, a subjetividades en proceso, mediante prácticas objetivas, sensibles y de saber.

This paper thinks the experience from a body immanent, unique and incarnate. We started this journey with some twists review exercised by philosophers, anthropologists and sociologists on the hegemonic paradigm of modernity to then relate this to the practices of corporal education. Interested, here, to go beyond the dualistic body and categorized to address a body experience, he says, of subjectivity in a process, through practices objective, sensitive and knowing.

Este ensaio pensa a experiência desde um corpo imanente, singular e encarnado. Iniciamos essa trajetória com a revisão de algumas torções exercidas por filósofos, antropólogos e sociólogos sobre o paradigma hegemônico na modernidade para, posteriormente, relacioná-lo com as práticas da educação corporal. Interessa, aqui, ir mais além do corpo dissecado e categorizado para dirigir-se a um corpo da experiência, quer dizer, a uma subjetividade em processo, mediante práticas objetivas, sensíveis e de saber.

Protocolo diferenciado para terapia nutricional na esclerose lateral amiotrófica / Special protocol to nutritional therapy in amyotrophic lateral sclerosis

OBJETIVO: Discutir a terapia nutricional na Esclerose Lateral Amiotrófica (ELA), compartilhando um protocolo elaborado e utilizado em ambulatório especializado. MATERIAL E MÉTODOS: A fundamentação teórica desse artigo foi baseada na literatura científica publicada nas bases de dados PubMed e ISI Web of Science, utilizando os descritores "amyrotrophic lateral sclerosis" and "nutrition". RESULTADOS E DISCUSSÃO: Em síntese, a ELA é uma doença neurodegenerativa rara, com prognóstico desfavorável e tratamento paliativo. A desnutrição é bastante frequente nessa doença e aumenta o risco de morte dos pacientes. Assim, a terapia nutricional é imprescindível e deve estar integrada a uma assistência multidisciplinar. O monitoramento nutricional é recomendado pelo menos a cada três meses, incluindo avaliação nutricional e prescrição de dieta hipercalórica e hiperproteica, com adequada quantidade hídrica e de fibras. Em adição, os micronutrientes, sobretudo os antioxidantes, devem atingir a Ingestão Diária Recomendada. Modificações na consistência da dieta para tratar a disfagia são indicadas e a nutrição enteral deve ser desmistificada entre os pacientes e cuidadores. Esses pacientes são candidatos potenciais para uso da nutrição enteral, a qual deve ser indicada em casos de disfagia significativa ou prejuízo da função respiratória associada com baixa ingestão alimentar, índice de massa corporal menor que 18,5 ou 22,0 kg/m2 (para adultos e idosos, respectivamente) e/ou perda de peso acima de 10%. CONCLUSÃO: Sugere-se a padronização da terapia nutricional na ELA e a instituição de protocolo diferenciado na prática clínica. Com isso, a desnutrição pode ser evitada ou minimizada, contribuindo para melhor qualidade de vida e sobrevida desses pacientes

OBJECTIVE: To discuss the nutritional therapy in Amyotrophic Lateral Sclerosis (ALS), sharing a protocol performed and used by a specialized ambulatory care service. MATERIAL AND METHODS: The theoretical foundation of this paper was based on the literature published in both PubMed and ISI Web of Science, using "amyrotrophic lateral sclerosis" and "nutrition" as keywords. RESULTS AND DISCUSSION: In brief, ALS is a rare neurodegenerative disease with poor prognosis and palliative treatment. Malnutrition is very common in these patients and increases the risk of death among them. Nutritional therapy is essential and must be integrated into a multidisciplinary care. Nutritional monitoring is recommended at least once every three months. Nutritional assessment, high-calorie and highprotein diet with an adequate amount of water and fiber are recommended. In addition, micronutrients, especially antioxidants, must reach the Recommended Dietary Allowances. A diet texture modification for dysphagia is indicated and enteral nutrition should be demystified to patients and care givers during the follow-up care. ALS patients are potential candidates to use enteral nutrition, which should be indicated in cases of significant dysphagia or impaired respiratory function associated with low food intake, body mass index less than 18.5 or 22.0 kg/m² (for adults or elderlies, respectively), and/or body weight loss above 10%. CONCLUSION: We suggest the standardization of nutritional therapy in ALS and the establishment of a distinct protocol in clinical practice. Thus, malnutrition can be avoided or minimized, contributing to a better quality of life and survival of these patients

Bone marrow-derived mononuclear cells vs. mesenchymal stromal cells in experimental allergic asthma.

We compared the effects of bone marrow-derived mononuclear cells (BMMCs) and mesenchymal stromal cells (MSCs) on airway inflammation and remodeling and lung mechanics in experimental allergic asthma. C57BL/6 mice were sensitized and challenged with ovalbumin (OVA group). A control group received saline using the same protocol. Twenty-four hours after the last challenge, groups were further randomized into subgroups to receive saline, BMMCs (2×10(6)) or MSCs (1×10(5)) intratracheally. BMMC and MSC administration decreased cell infiltration, bronchoconstriction index, alveolar collapse, collagen fiber content in the alveolar septa, and interleukin (IL)-4, IL-13, transforming growth factor (TGF)-ß and vascular endothelial growth factor (VEGF) levels compared to OVA-SAL. Lung function, alveolar collapse, collagen fiber deposition in alveolar septa, and levels of TGF-ß and VEGF improved more after BMMC than MSC therapy. In conclusion, intratracheal BMMC and MSC administration effectively modulated inflammation and fibrogenesis in an experimental model of asthma, but BMMCs was associated with greater benefit in terms of reducing levels of fibrogenesis-related growth factors.

Fueling open-source drug discovery: 177 small-molecule leads against tuberculosis.

With the aim of fuelling open-source, translational, early-stage drug discovery activities, the results of the recently completed antimycobacterial phenotypic screening campaign against Mycobacterium bovis BCG with hit confirmation in M. tuberculosis H37Rv were made publicly accessible. A set of 177 potent non-cytotoxic H37Rv hits was identified and will be made available to maximize the potential impact of the compounds toward a chemical genetics/proteomics exercise, while at the same time providing a plethora of potential starting points for new synthetic lead-generation activities. Two additional drug-discovery-relevant datasets are included: a) a drug-like property analysis reflecting the latest lead-like guidelines and b) an early lead-generation package of the most promising hits within the clusters identified.

Comparação de três programas computacionais utilizados na avaliação de recordatórios alimentares 24 horas / Comparison of three softwares used for evaluating of 24-hour food recall / Comparación de tres programas de ordenador usados en la evaluación de recordatorios 24 h

A avaliação do consumo alimentar tem um papel importante na área de Nutrição e Saúde. Para tanto, são necessários métodos apropriados para estimar a ingestão de alimentos e nutrientes. O mercado da informática vem desenvolvendo diversos programas computacionais especializados em nutrição clínica. No entanto, a escolha do programa mais adequado tem sido uma decisão difícil em função das características operacionais disponíveis em cada um. Este estudo objetivou comparar três programas computacionais (Dietwin® profissional, Dietpro® 5i e Avanutri® revolution) utilizados na análise química nutricional de dez Recordatórios Alimentares de 24 horas oriundos de pacientes com Esclerose Lateral Amiotrófica, atendidos no Hospital Universitário da UFRN. Não houve diferença estatística entre os programas computacionais, com relação à energia, macronutrientes e micronutrientes. Todavia, foram detectadas divergências entre as gramaturas estipuladas para medidas caseiras de alguns alimentos. Além disso, observou-se quantificação equivocada do teor de ferro e cobre em dois alimentos. Conclui-se que é preciso ter cautela na escolha de um programa computacional especializado em nutrição clínica, pois poderá superestimar ou subestimar valores de energia ou nutrientes numa dieta prescrita ou consumida. Em adição, cuidado especial deve ser dado à origem das informações que alimentam o banco de dados desses programas, devendo ser as mais fidedignas possíveis.

Food intake assessment has an important role in nutrition research and health. For this purpose, right methods are needed to estimate appropriate intake of food and nutrients. The informatics market has developed several specialized computer programs in clinical nutrition . However, choosing the most appropriate program has been a difficult decision due all of operational features available in each one. This study aimed to compare three computer programs (Dietwin ® professional DietPro ® 5i and Avanutri Revolution ®) used in chemical analysis of ten 24-hour food recall from ten Amyotrophic Lateral Sclerosis patients, attending in by specific Multidisciplinary Team at Federal University of Rio Grande do Norte. There was no statistical difference between the three computer programs related to energy, macronutrients and micronutrients. Despite this, some differences were detected like measure portion food sizes. Moreover, there was wrong quantification of iron and copper content in two foods. We conclude that care should be taken to choose a computer program in clinical nutrition, because it can overestimate or underestimate values of calories and nutrients in a specific diet. In addition, it is necessary to be especially careful in the information sources that will feed the database of these programs. They should be as reliable as possible.

La evaluación de la ingesta alimentaria tiene un papel importante en la investigación en nutrición y salud. Para evaluar la ingesta de alimentos de un individuo se requieren métodos adecuados para la estimación de la ingesta de alimentos y nutrientes. El mercado de la informática ha desarrollado varios programas informáticos especializados en nutrición clínica. Sin embargo, elegir el programa más apropiado ha sido una decisión difícil a la luz de las características disponibles operativo. Este estudio tuvo por objetivo comparar los tres programas de ordenador (Dietwin ® profesional DietPro ® 5i y Avanutri Revolución ®) utilizados en el análisis químico de de recordatorios 24 h de pacientes con Esclerosis Amiotrófica Lateral. No hubo diferencia estadística entre los programas de ordenador, con respecto a la energía, macronutrientes y micronutrientes. Sin embargo, se detectaron diferencias entre los pesos fijados para tamaños de las porciones de algunos alimentos. Además, el contenido de hierro y el cobre se equivocaron en dos alimentos. El estudio demostró que se debe tener cuidado al elegir el mejor programa en la nutrición clínica, ya que puede sobreestimar o subestimar los valores de las calorías y nutrientes de una dieta prescrita o consumido. Además, la atención especial se debe dar a la fuente de la información introducida en la base de datos de estos programas debe ser lo más fiable posible.

Uso de medicamentos para perda de peso e índice de massa corporal em universitários do Vale do Araguaia (MT/GO), Amazônia Legal / Use of weight loss drugs and body mass index among academicians from Vale do Araguaia (MT/GO), Legal Amazon

JUSTIFICATIVA E OBJETIVOS: A obesidade está associada a diversas doenças, como a hipertensão arterial, diabetes mellitus tipo 2, doenças cardiovasculares e cerebrovasculares, além do aumento do risco de neoplasias. No Brasil, o consumo de moderadores de apetite é um dos maiores do mundo. Deste modo, o objetivo deste estudo foi conhecer a prevalência de consumo de medicamentos para perda de peso e a prevalência de sobrepeso em população de estudantes universitários. MÉTODO: Foram avaliados 487 alunos do Campus Universitário do Araguaia, UFMT. Foi realizada avaliação do índice de massa corpórea (IMC) e aplicação de questionário para avaliação dos medicamentos para perda de peso mais consumidos, tempo de consumo, ocorrência de efeitos adversos, acompanhamento médico e motivo para seu uso. RESULTADOS: Dos entrevistados, 9% utilizaram medicamentos com intuito de emagrecer, dentre estes 47,7% estavam com IMC normal e 88,6% eram mulheres. A prevalência de sobrepeso nos estudantes foi de 22,9% dentre os homens e 9,6% dentre as mulheres. Os fármacos mais utilizados foram a quitosana (13,1%), seguidos pela alcachofra (Cynara scolymus L.), chá verde (Camelia sinensis), femproporex e sibutramina, com 6,7% cada. A reação adversa mais citada foi boca seca (21,6%). Dentre os estudantes, 41% afirmaram ter obtido informações acerca do medicamento utilizado com um médico. Além do medicamento para emagrecer, 52,5% dos entrevistados afirmaram utilizar dieta de restrição alimentar, 30% fizeram dieta e exercícios físicos. CONCLUSÃO: A maioria das mulheres que utilizaram medicamentos para perda de peso não precisavam fazê-lo.

BACKGROUND AND OBJECTIVES: Obesity associated with many diseases, such as arterial hypertension, type 2 diabetes mellitus, cardiovascular and cerebrovascular diseases, beyond the increased risk of neoplastic disorders. In Brazil, the consumption of anorexigen drugs is one of the most high in the world. Then, the objective of this work was to know the prevalence of overweight and use of weight loss drugs in a population of university students. METHOD: 487 students from the "Instituto Universitário do Araguaia", Universidade Federal de Mato Grosso (UFMT) were analyzed. Beyond the body mass index (BMI), a questionnaire was used to evaluate the most consumed weight loss drugs, time of drug use, occurrence of adverse health effects, medical consulting, and declared motive for using those drugs. RESULTS: Among the interviewed, 9.0% used drugs for weight loss, and between those 47.7% presented normal body mass index (BMI), and 88.6% were female. The prevalence of overweight was 22.9% for male and 9.6% for female students. The most used weight loss drugs were chitosan (13.1%), followed by alcachofra (Cynara scolymus L.), green tea (Camelia sinensis), fenproporex and sibutramine, with 6.7% each drug. The most frequent related adverse health effect was dry mouth (21.6%). Among the students, 41.0% declared had obtained drug information use with a medical doctor. Beyond use of weight loss drugs, 52.5% of the students declared use food restriction diets, and 30.0% were involved in both food restriction diets and practice of physical exercises. CONCLUSION: The majority of women had used weight loss drugs must not use it because of their normal body weight.

Falcipain inhibitors: optimization studies of the 2-pyrimidinecarbonitrile lead series.

Falcipain-2 and falcipain-3 are papain-family cysteine proteases of the malaria parasite Plasmodium falciparum that are responsible for host hemoglobin hydrolysis to provide amino acids for parasite protein synthesis. Different heteroarylnitrile derivatives were studied as potential falcipain inhibitors and therefore potential antiparasitic lead compounds, with the 5-substituted-2-cyanopyrimidine chemical class emerging as the most potent and promising lead series. Through a sequential lead optimization process considering the different positions present in the initial scaffold, nanomolar and subnanomolar inhibitors at falcipains 2 and 3 were identified, with activity against cultured parasites in the micromolar range. Introduction of protonable amines within lead molecules led to marked improvements of up to 1000 times in activity against cultured parasites without noteworthy alterations in other SAR tendencies. Optimized compounds presented enzymatic activities in the picomolar to low nanomolar range and antiparasitic activities in the low nanomolar range.