Hipertensos assistidos em serviço de atenção secundária: risco cardiovascular e determinantes sociais de saúde / Hypertense individuals assisted in secondary care service: cardiovascular risk and social determinants of health

Resumo Introdução Na perspectiva dos determinantes sociais de saúde, a Hipertensão Arterial Sistêmica apresenta complexa natureza multifatorial. É fator de risco cardiovascular, influenciado por aspectos comportamentais, econômicos, sociais, políticos e ambientais. Objetivo Investigar a relação entre determinantes sociais de saúde e risco cardiovascular global em hipertensos assistidos em serviço da atenção secundária do Sistema Único de Saúde. Método Estudo seccional analítico, com pacientes do Centro Hiperdia, no norte de Minas Gerais, Brasil. Dados de determinantes sociais foram coletados por meio de questionário estruturado. A classificação do risco cardiovascular (alto, moderado e baixo) deu-se a partir de dados clínicos. A estatística considerou nível de significância 5%. Resultados Entre 231 participantes, a maioria (64,1%) era de alto risco cardiovascular, associado aos dados clínicos: elevada pressão arterial sistólica (p=0,04) e maior tempo de diagnóstico (p=0,01). O alto risco cardiovascular foi associado aos determinantes sociais: satisfação com acesso aos serviços de saúde (p=0,02) e ambiente físico saudável (p=0,02). Conclusão Apesar de a satisfação com os serviços de saúde e com o ambiente físico terem apresentado resultados reversos, sugere-se fortalecer políticas e práticas de atenção à saúde, que reconheçam diferentes determinantes e previnam a gravidade do risco cardiovascular.

Abstract Background In the perspective of the social determinants of health, Systemic Arterial Hypertension presents complex multifactorial nature. This cardiovascular risk factor is influenced by behavioral, economic, social, political and environmental aspects. Objective To investigate the relationship between social determinants of health and global cardiovascular risk in hypertensive patients assisted in the secondary care service of the Unified Health System. Method An analytical sectional study with patients from Centro Hiperdia in Northern Minas Gerais, Brazil. Data of social determinants were collected through a structured questionnaire. The classification of cardiovascular risk (high, moderate and low) was based on clinical data. The statistic considered significance level 5%. Results Among 231 participants, the majority (64.1%) presented high cardiovascular risk, associated with clinical data: high systolic blood pressure (p=0.04) and longer diagnostic time (p=0.01). High cardiovascular risk was associated with social determinants: satisfaction with access to health services (p=0.02) and healthy physical environment (p=0.02). Conclusion Although satisfaction with the health services and the physical environment presented reversed results, we suggest the strengthening of health care policies and practices that recognize different determinants, and prevent the severity of cardiovascular risk.

The Impact of COVID-19-Related Measures on the Solar Resource in Areas with High Levels of Air Pollution.

Restrictions enacted to reduce the spreading of COVID-19 have resulted in notably clearer skies around the world. In this study, we confirm that reduced levels of air pollution correlate with unusually high levels of clear-sky insolation in Delhi, India. Restrictions here were announced on March 19th, with the nation going into lockdown on March 24th. Comparing insolation data before and after these dates with insolation from previous years (2017 to 2019), we observe an 8.3% ± 1.7% higher irradiance than usual in late March and a 5.9% ± 1.6% higher one in April, while we find no significant differences in values from previous years in February or early March. Using results from a previous study, we calculated the expected increase in insolation based on measured PM2.5 concentration levels. Measurements and calculations agree within confidence intervals, suggesting that reduced pollution levels are a major cause for the observed increase in insolation.

Genetic and Epigenetic Biomarkers of Immune Checkpoint Blockade Response.

Checkpoint inhibitor therapy constitutes a promising cancer treatment strategy that targets the immune checkpoints to re-activate silenced T cell cytotoxicity. In recent pivotal trials, immune checkpoint blockade (ICB) demonstrated durable responses and acceptable toxicity, resulting in the regulatory approval of 8 checkpoint inhibitors to date for 15 cancer indications. However, up to ~85% of patients present with innate or acquired resistance to ICB, limiting its clinical utility. Current response biomarker candidates, including DNA mutation and neoantigen load, immune profiles, as well as programmed death-ligand 1 (PD-L1) expression, are only weak predictors of ICB response. Thus, identification of novel, more predictive biomarkers that could identify patients who would benefit from ICB constitutes one of the most important areas of immunotherapy research. Aberrant DNA methylation (5mC) and hydroxymethylation (5hmC) were discovered in multiple cancers, and dynamic changes of the epigenomic landscape have been identified during T cell differentiation and activation. While their role in cancer immunosuppression remains to be elucidated, recent evidence suggests that 5mC and 5hmC may serve as prognostic and predictive biomarkers of ICB-sensitive cancers. In this review, we describe the role of epigenetic phenomena in tumor immunoediting and other immune evasion related processes, provide a comprehensive update of the current status of ICB-response biomarkers, and highlight promising epigenomic biomarker candidates.

Hypertension bearers with high risk/big risk of cardiovascular diseases and socioeconomic and health indicators.

OBJECTIVE: To correlate the number of hypertensive patients with high and very high risk for cardiovascular diseases with socioeconomic and health indicators. METHODS: An ecological study carried out from the National Registry of Hypertension and Diabetes (SisHiperDia). The variable "hypertensive patients with high and very high risk" was correlated with the Human Development Index, health care costs and services, average household income per capita, per capita municipal income, number of hospital admissions in SUS, number of medical consultations in the SUS and specific mortality due to diseases of the circulatory system, considering the 27 federative units of Brazil. The data was processed in software IBM Statistical Package for the Social Sciences (SPSS) Statistics, version 22.00. The statistical analysis considered the level of significance p<0.05. RESULTS: Brazilian states with more hypertensive registries in high/very high risk spend more on public health, fewer people reach the elderly age group and more deaths from diseases of the circulatory system (p<0.05). The very high risk stratum correlated with more physicians per population (p<0.05). CONCLUSION: Systemic arterial hypertension has a direct impact on life expectancy and also on the economic context, since when it evolves to high and very high risk for cardiovascular diseases, it generates more expenses in health and demand more professionals, burdening the public health system. Monitoring is necessary in order to consolidate public policies to promote the health of hypertensive individuals.

Hypertension bearers with high risk/big risk of cardiovascular diseases and socioeconomic and health indicators

SUMMARY OBJECTIVE To correlate the number of hypertensive patients with high and very high risk for cardiovascular diseases with socioeconomic and health indicators. METHODS An ecological study carried out from the National Registry of Hypertension and Diabetes (SisHiperDia). The variable "hypertensive patients with high and very high risk" was correlated with the Human Development Index, health care costs and services, average household income per capita, per capita municipal income, number of hospital admissions in SUS, number of medical consultations in the SUS and specific mortality due to diseases of the circulatory system, considering the 27 federative units of Brazil. The data was processed in software IBM Statistical Package for the Social Sciences (SPSS) Statistics, version 22.00. The statistical analysis considered the level of significance p<0.05. RESULTS Brazilian states with more hypertensive registries in high/very high risk spend more on public health, fewer people reach the elderly age group and more deaths from diseases of the circulatory system (p<0.05). The very high risk stratum correlated with more physicians per population (p<0.05). CONCLUSION: Systemic arterial hypertension has a direct impact on life expectancy and also on the economic context, since when it evolves to high and very high risk for cardiovascular diseases, it generates more expenses in health and demand more professionals, burdening the public health system. Monitoring is necessary in order to consolidate public policies to promote the health of hypertensive individuals.

RESUMO OBJETIVO Correlacionar o número de cadastros de hipertensos com risco alto e muito alto para doenças cardiovasculares com os indicadores socioeconômicos e de saúde. MÉTODOS Estudo ecológico realizado a partir do Sistema Nacional de Cadastro de Hipertensão e Diabetes (SisHiperDia). A variável "hipertensos com risco alto e muito alto" foi correlacionada ao Índice de Desenvolvimento Humano, gastos com ações e serviços de saúde, renda média domiciliar per capita, renda municipal per capita, número de internações hospitalares no SUS, número de consultas médicas no SUS e mortalidade específica por doenças do aparelho circulatório, considerando as 27 unidades federativas do Brasil. Os dados foram processados no software IBM Statistical Package for the Social Sciences (SPSS) Statistics, versão 22.00. A análise estatística considerou o nível de significância p < 0,05. RESULTADOS Estados brasileiros com mais cadastros de hipertensos em riscos alto/muito alto gastam mais na saúde pública, menos pessoas alcançam a faixa etária idosa e há mais mortes por doenças do aparelho circulatório (p < 0,05). O estrato de risco muito alto correlacionou com mais médicos por habitantes (p < 0,05). CONCLUSÃO A hipertensão arterial sistêmica impacta diretamente a expectativa de vida e também o contexto económico, pois, quando evolui para risco alto e muito alto, para as doenças cardiovasculares, gera mais gastos em saúde e demanda mais profissionais, onerando o sistema público de saúde. É necessário monitoramento, em busca da consolidação das políticas públicas de promoção da saúde dos hipertensos.

Nurr1 and Retinoid X Receptor Ligands Stimulate Ret Signaling in Dopamine Neurons and Can Alleviate α-Synuclein Disrupted Gene Expression.

α-synuclein, a protein enriched in Lewy bodies and highly implicated in neurotoxicity in Parkinson's disease, is distributed both at nerve terminals and in the cell nucleus. Here we show that a nuclear derivative of α-synuclein induces more pronounced changes at the gene expression level in mouse primary dopamine (DA) neurons compared to a derivative that is excluded from the nucleus. Moreover, by RNA sequencing we analyzed the extent of genome-wide effects on gene expression resulting from expression of human α-synuclein in primary mouse DA neurons. The results implicated the transcription factor Nurr1 as a key dysregulated target of α-synuclein toxicity. Forced Nurr1 expression restored the expression of hundreds of dysregulated genes in primary DA neurons expressing α-synuclein, and therefore prompted us to test the possibility that Nurr1 can be pharmacologically targeted by bexarotene, a ligand for the retinoid X receptor that forms heterodimers with Nurr1. Although our data demonstrated that bexarotene was ineffective in neuroprotection in rats in vivo, the results revealed that bexarotene has the capacity to coregulate subsets of Nurr1 target genes including the receptor tyrosine kinase subunit Ret. Moreover, bexarotene was able to restore dysfunctional Ret-dependent neurotrophic signaling in α-synuclein-overexpressing mouse DA neurons. These data highlight the role of the Nurr1-Ret signaling pathway as a target of α-synuclein toxicity and suggest that retinoid X receptor ligands with appropriate pharmacological properties could have therapeutic potential in Parkinson's disease. SIGNIFICANCE STATEMENT: How α-synuclein, a protein enriched in Lewy bodies in Parkinson's disease, is causing neuropathology in dopamine neurons remains unclear. This study elucidated how α-synuclein is influencing gene expression and how Nurr1, a transcription factor known to protect dopamine neurons against α-synuclein toxicity, can counteract these effects. Moreover, given the protective role of Nurr1, this study also investigated how Nurr1 could be pharmacologically targeted via bexarotene, a ligand of Nurr1's heterodimerization partner retinoid X receptor (RXR). The results showed that RXR ligands could increase neurotrophic signaling, but provided a mixed picture of its potential in a Parkinson's disease rat model in vivo. However, this study clearly emphasized Nurr1's neuroprotective role and indicated that other RXR ligands could have therapeutic potential in Parkinson's disease.

Justiça distributiva no serviço de saúde especializado e no acesso a medicamentos / Distributive justice in specialized health service and in access to medication / Justicia distributiva en el servicio de salud especializado y en el acceso a medicamentos

Quando se fala de doenças crônicas e do sistema público de saúde, a escassez de recursos está sempre em pauta. O estudo analisou o referenciamento e o acesso à medicação em indivíduos assistidos pelo serviço público estadual Hiperdia. Trata-se de pesquisa transversal, com 250 indivíduos referenciados para esse nível secundário de atenção à hipertensão e diabetes. Investigaram-se critérios biológicos, acesso aos medicamentos, perfil sociodemográfico e econômico e condição de saúde. O nível de significância estatística foi de 5%. O referenciamento correto foi de 64,0%, embora incorreto para quase metade dos que utilizaram o transporte público municipal. O acesso total à medicação (69,6%) estava associado à menor renda familiar (p < 0,05). A discussão, fundamentada no princípio da justiça distributiva, concluiu pela recomendação de melhor capacitação dos profissionais no referenciamento de serviços assistenciais, com redução do desperdício em transporte público e atenção especializada, além do que, tal investimento deve ser revertido em maior distribuição gratuita de medicamentos.

When speaking of chronic illnesses and the public health system, the lack of resources is on the agenda. The study analyzed the referencing and access to medication in individuals assisted by the State Public Service Hiperdia. It is a transversal study, with 250 individuals referred for this secondary level of attention to hypertension and diabetes. The study investigated biological criteria, access to medicine, socio-demographic and economic profile and health condition. The level of statistical significance was 5%. The correct referencing was 64.0%, although incorrect for nearly half of those that used municipal public transportation. The total access to medicine (69.6%) was associated with the lowest family incomes (p < 0.05). The discussion, based on the principle of distributive justice, was concluded by recommending better training of professionals in referencing assistance services, with a reduction of waste in public transport and specialized attention, because such investment should be reverted to a wider distribution of medicine.

Cuando se habla de enfermedades crónicas y sistema público de salud, la escasez de recursos está en agenda. El estudio analizó la derivación y el acceso a la medicación de individuos asistidos por el servicio público estatal Hiperdia. Se trata de un estudio transversal, con 250 individuos derivados hacia el nivel secundario, para la atención de hipertensión y diabetes. Se investigaron criterios biológicos, acceso a los medicamentos, perfil sociodemográfico y económico y condición de salud. El nivel de significación estadística fuel del 5%. La derivación correcta fue del 64,0%, aunque incorrecto para casi la mitad de los que utilizaron transporte público municipal. El acceso total a la medicación (69,6%) estuvo asociado al menor ingreso familiar (p < 0,05). La discusión, basada en el principio de la justicia distributiva, concluyó recomendando mejor capacitación de los profesionales en la derivación de servicios asistenciales, con reducción del gasto en transporte público y atención especializada, pues tal inversión debe ser traducida en mayor distribución gratuita de medicamentos.

Dopaminergic control of autophagic-lysosomal function implicates Lmx1b in Parkinson's disease.

The role of developmental transcription factors in maintenance of neuronal properties and in disease remains poorly understood. Lmx1a and Lmx1b are key transcription factors required for the early specification of ventral midbrain dopamine (mDA) neurons. Here we show that conditional ablation of Lmx1a and Lmx1b after mDA neuron specification resulted in abnormalities that show striking resemblance to early cellular abnormalities seen in Parkinson's disease. We found that Lmx1b was required for the normal execution of the autophagic-lysosomal pathway and for the integrity of dopaminergic nerve terminals and long-term mDA neuronal survival. Notably, human LMX1B expression was decreased in mDA neurons in brain tissue affected by Parkinson's disease. Thus, these results reveal a sustained and essential requirement of Lmx1b for the function of midbrain mDA neurons and suggest that its dysfunction is associated with Parkinson's disease pathogenesis.

Morphological and anatomical characterization of the digestive tract of Centropomus parallelus and C. undecimalis / Caracterização Morfológica e Anatômica do Tubo Digestório de Centropomus parallelus e C. undecimalis

Centropomus parallelus and C. undecimalis are the most common species of Centropomidae in Brazil. Some authors attribute their failure to grow under in artificial conditions due to limited knowledge on the morphological and functional development of their digestive system and on nutrition requirements of both species. Current research characterizes histologically and histochemically the digestive tract of C. parallelus and C. undecimalis to provide a histophysiological assessment for studies related to their nutritional needs. In the esophagus, the mucous cells in the epithelium stained positively for PAS and AB. In the stomach, positive reactions to PAS and negative to AB respectively occurred on surface and mucous cells in the epithelium and in the lamina propria. In the intestine, goblet cells showed ratio similarity, with mucus being positive in AB and PAS. A greater concentration of these cells existed in the middle and distal intestine, with a greater increase of secretions when compared to those in the proximal intestine. Results show that C. parallelus and C.undecimalis display the main features of the digestive tract of carnivorous fish, a well-developed stomach and a relatively short intestine. In fact, they give insights for future studies on the mechanisms related to the species's digestive and absorptive physiology.

Centropomus parallelus e C. undecimalis são as espécies mais comuns de Centropomidae no Brasil. Alguns autores atribuem o insucesso no seu cultivo devido ao escasso conhecimento sobre o desenvolvimento morfológico e funcional do sistema digestório, assim como o desconhecimento das exigências nutricionais das espécies. Dessa forma realizou-se o presente trabalho, com o objetivo de caracterizar histológica e histoquimicamente o tubo digestório de C. parallelus e C. undecimalis, para estudos histofisiológicos relacionados às necessidades nutricionais deste peixe. No esôfago, as células mucosas, presentes no epitélio coraram-se positivamente tanto em PAS como em AB. No estômago, as células superficiais e mucosas presentes no epitélio e na lâmina própria respectivamente, apresentaram reações positivas em PAS e negativa em AB. No intestino as células caliciformes apresentaram similaridade na proporção entre os mucos sendo positivos tanto em PAS como em AB; nos intestinos médio e distal observou-se uma maior concentração destas células, resultando em uma quantidade maior de secreções em comparação ao intestino proximal. Através dos resultados observados, conclui-se que o C. parallelus e C. undecimalis exibem as principais características do trato digestório de peixes carnívoros, como um estômago bem desenvolvido e um intestino relativamente curto. Estes resultados darão subsídios para futuros estudos sobre mecanismos da fisiologia digestiva e absortiva desta espécie.

Morphological and anatomical characterization of the digestive tract of Centropomus parallelus and Centropomus undecimalis - doi: 10.4025/actascibiolsci.v35i4.14352

Centropomus parallelus and Centropomus undecimalis are the most common species of Centropomidae in Brazil. Some authors attribute their failure to grow under in artificial conditions due to limited knowledge on the morphological and functional development of their digestive system and on nutrition requirements of both species. Current research characterizes histologically and histochemically the digestive tract of Centropomus parallelus and Centropomus undecimalis to provide a histophysiological assessment for studies related to their nutritional needs. In the esophagus, the mucous cells in the epithelium stained positively for PAS and AB. In the stomach, positive reactions to PAS and negative to AB respectively occurred on surface and mucous cells in the epithelium and in the lamina propria. In the intestine, goblet cells showed ratio similarity, with mucus being positive in AB and PAS. A greater concentration of these cells existed in the middle and distal intestine, with a greater increase of secretions when compared to those in the proximal intestine. Results show that Centropomus parallelus and Centropomus undecimalis display the main features of the digestive tract of carnivorous fish, a well-developed stomach and a relatively short intestine. In fact, they give insights for future studies on the mechanisms related to the species´s digestive and absorptive physiology.

Papel do ecocardiograma no diagnóstico de displasia arritmogênica do ventrículo direito / Role of echocardiography in diagnosis of arrhythmogenic right ventricular dysplasia

A displasia arritmogênica do Ventrículo Direito (DAVD) é uma doença cardíaca estrutural, causada por mutações genéticas que levam à substituição progressiva de células miocárdicas por tecido fibrogorduroso, levando seu portador a desenvolver arritmiasmalignas e alta probabilidade de morte súbita. O ecocardiograma é essencial na avaliação de pacientes com história de síncope, para diagnóstico diferencial de várias patologias, dentre elas a DAVD.

The colayer method as an efficient way to genetically modify mesencephalic progenitor cells transplanted into 6-OHDA rat model of Parkinson's disease.

Exogenous cell replacement represents a potent treatment option for Parkinson's disease. However, the low survival rate of transplanted dopaminergic neurons (DA) calls for methodological improvements. Here we evaluated a method to combine transient genetic modification of neuronal progenitor cells with an optimized cell culture protocol prior to intrastriatal transplantation into 6-hydroxydopamine (6-OHDA) unilateral lesioned rats. Plasmid-based delivery of brain-derived neurotrophic factor (BDNF) increases the number of DA neurons, identified by tyrosine hydroxylase immunoreactivity (TH-ir), by 25% in vitro, compared to enhanced green fluorescence protein (EGFP)-transfected controls. However, the nucleofection itself, especially the cell detachment and reseeding procedure, decreases the TH-ir neuron number to 40% compared with nontransfected control cultures. To circumvent this drawback we established the colayer method, which contains a mix of nucleofected cells reseeded on top of an adherent sister culture in a ratio 1:3. In this setup TH-ir neuron number remains high and could be further increased by 25% after BDNF transfection. Comparison of both cell culture procedures (standard and colayer) after intrastriatal transplantation revealed a similar DA neuron survival as seen in vitro. Two weeks after grafting TH-ir neuron number was strongly reduced in animals receiving the standard EGFP-transfected cells (271 ± 62) compared to 1,723 ± 199 TH-ir neurons in the colayer group. In contrast to the in vitro results, no differences in the number of grafted TH-ir neurons were observed between BDNF, EGFP, and nontransfected colayer groups, neither 2 nor 13 weeks after transplantation. Likewise, amphetamine and apomorphine-induced rotational behavior improved similarly over time in all groups. Nevertheless, the colayer protocol provides an efficient way for neurotrophic factor release by transplanted progenitor cells and will help to study the effects of candidate factors on survival and integration of transplanted DA neurons.

Ecocardiograma na investigação e acompanhamento de paciente neurotropênico febril com diagnóstico de aspergilose cardíaca / Echocardiogram in the investigation and attendance of the febrile neutropenic patient with diagnosis of cardiac aspergillosis

Neste relato, é apresentada a história clínica de um paciente jovem, portador de aplasia medular, em propedêutica para neutropenia febril. Ecocardiograma transesofágico revelou massa intra-atrial esquerda de grandes dimensões, com alto risco de embolização sistêmica. Foi submetido a cirurgia para ressecção da massa atrial, sendo o material enviado para o exame anatomopatológico, o qual revelou trombo infectado por Aspergillus sp (endocardite fúngica). Ecocardiogramas realizados no 7º dia pós-operatório revelaram rápida recidiva da massa intra-atrial. Paciente evoluiu com piora clínica, insuficiência respiratória, parada cardiorrespiratória e óbito.

We present here a young patient’s clinical history, bearer of medular aplasy, in the investigation for febrile neutropenia. Transesophagealechocardiogram showed an intra-left atrial mass of great dimensions with high risk of systemic embolization. He underwent to surgery for ressection of the atrial mass and the material was sent to anatomopathology study that revealed infected thrombus by Aspergillus sp (fungal endocarditis). Echocardiogram accomplished in 7th postoperative day revealed fast recurrence of the intra-atrial mass. Patient developed with clinical worsening, breathing insufficiency, cardiorespiratory arrest and death.

Topology of intrastriatal dopaminergic grafts determines functional and emotional outcome in neurotoxin-lesioned rats.

Many Parkinson's disease (PD) patients suffer from anxiety disorders, which often precede the onset of classical motor symptoms. So far, there is no evidence from randomized, placebo-controlled trials for successful treatment of anxiety in patients with PD. Grafts of fetal nigral neurons are currently explored as a restorative cell therapy for PD. In PD animal models, intrastriatal transplantations of embryonic dopaminergic neurons have been shown to ameliorate behavioral defects. In our previous study we showed that expanded and differentiated neural progenitors improved drug-induced rotation behavior and posture balance as a more complex motor task. However, it is not clear whether grafting of these cells affected spontaneous locomotor activity and anxiety-like behavior in 6-OHDA lesioned rats. Therefore, we analyzed behavior of control, lesioned, sham-transplanted, and transplanted rats using open field (OF) and elevated plus maze (EPM). After unilateral 6-OHDA lesion of the medial forebrain bundle, we observed reduced locomotor activity in the EPM (wall-rearing, entries in closed arms) in lesioned and sham-transplanted rats, which correlated with the loss of dopaminergic neurons and apomorphine-induced rotation behavior. Furthermore, anxiety-like behavior in the EPM (entries and time in open arms) was increased in lesioned and sham-transplanted rats. Although exogenous cell replacement improved apomorphine-induced rotation behavior, locomotor activity and anxiety-like behavior was not reconstituted in transplanted rats. However, we provided evidence for an interaction of locomotor activity/anxiety-like behavior with graft localization in the host striatum. These results emphasize the crucial role of graft localization for benefit of restorative cell therapy for PD.

Characterization and differentiation potential of rat ventral mesencephalic neuronal progenitor cells immortalized with SV40 large T antigen.

Neuronal progenitor cells (NPCs) possess high potential for use in regenerative medicine. To overcome their limited mitotic competence, various immortalization strategies have been applied that allow their prolonged maintenance and expansion in vitro. Such immortalized cells can be used for the design and discovery of new cell-based therapies for neurodegenerative diseases, such as Parkinson's disease. We immortalized rat ventral mesencephalic NPCs by using SV40 large T antigen (SV40Tag). All cell clones displayed a two- to three-fold higher proliferation rate compared with the primary cells. In order to induce dopaminergic differentiation of generated cell clones, both glial-derived neurotrophic factor and di-butyryl cyclic adenosine monophosphate were applied. Treated cells were then characterized regarding the expression of dopaminergic lineage markers, differentiation of various cell populations, calcium imaging in the presence of kainate, and immunohistochemistry after intrastriatal transplantation. Treated cells displayed morphological maturation, and calcium imaging revealed neuronal properties in the presence of kainate. These cells also expressed low mRNA levels of the dopamine transporter and tyrosine hydroxylase (TH), although no TH-immunopositive neurons were found. Intrastriatal transplantation into the neurotoxin-lesioned rats did not induce further differentiation. As an alternative approach, we silenced SV40Tag with short interfering RNA, but this was not sufficient to trigger differentiation into dopaminergic neurons. Nevertheless, neuronal and glial cells were detected as shown by beta-tubulin type III and glial fibrillary acidic protein staining, respectively. SV40Tag cells are suitable for carrying out controlled genetic modifications as shown by overexpression of enhanced green fluorescence protein after efficient non-viral transfection.

Avaliação do conhecimento sobre detecção precoce do câncer dos estudantes de medicina de uma universidade pública / Evaluation of medical students knowledge on early cancer detection in a public teaching hospital

Introdução: No Brasil, o câncer figura como a segunda causa de morte na população. O diagnóstico precoce exerce significativa influência sobre os índices de mortalidade, visto que um dos fatores que dificultam o tratamento é o estágio avançado em que a doença é descoberta. É importante que os estudantes conheçam as ações de detecção precoce recomendadas pelo Instituto Nacional de Câncer (INCA), pois os médicos recém-formados são aqueles que estarão na linha de frente social, podendo aplicá-las na prática e, assim, minimizar o avanço dessa doença. Objetivo: Verificar o conhecimento que os estudantes de medicina têm sobre as estratégias de detecção precoce para os cânceres de mama, próstata, pele, pulmão, colo do útero e colorretal, com base nas recomendaçõesdo INCA. Métodos: Estudo transversal realizado por meio de questionário sobre as ações de detecção precoceadotadas pelos estudantes dos 5º e 6º anos de medicina da Universidade Estadual de Montes Claros (MG). Osdados foram analisados no EPI-INFO. Resultados: De um total de 90 estudantes que estavam matriculados nos 5°e 6°anos de medicina, 66 participaram do estudo. Os cânceres os quais os estudantes julgaram mais incidentesforam: próstata (96,9 por cento), colo uterino (93,9 por cento) e mama (93,4 por cento). Conclusão: A maioria dos estudantes indicoumedidas de detecção precoce para os cânceres de próstata e pulmão que não são recomendadas pelo INCA, paraa população em geral. Os acadêmicos revelaram possuir um bom conhecimento sobre as estratégias de detecçãoprecoce para os cânceres de mama, colo uterino e pele. A maioria dos estudantes não distinguiu sinais precocesdos cânceres citados nas manifestações tardias.

The effect of modified polysialic acid based hydrogels on the adhesion and viability of primary neurons and glial cells.

In this study we present the enzymatic and biological analysis of polysialic acid (polySia) based hydrogel in terms of its degradation and cytocompatibility. PolySia based hydrogel is completely degradable by endosialidase enzyme which may avoid second surgery after tissue recovery. Viability assay showed that soluble components of polySia hydrogel did not cause any toxic effect on cultured Schwann cells. Moreover, green fluorescence protein transfected neonatal and adult Schwann cells, neural stem cells and dorsal root ganglionic cells (unlabelled) were seeded on polySia hydrogel modified with poly-L-lysine (Pll), poly-L-ornithine-laminin (porn-laminin) or collagen. Water soluble tetrazolium salt assay revealed that modification of the hydrogel significantly improved cell adhesion and viability. These results infer that polySia based scaffolds in combination with cell adhesion molecules and cells genetically modified to express growth factors would potentially be promising alternative in reconstructive therapeutic strategies.