A new immunochemotherapy schedule for visceral leishmaniasis in a hamster model.

The purpose of the present study was to evaluate the efficacy of the treatment with a recombinant cysteine proteinase from Leishmania, rldccys1, associated with allopurinol or miltefosine on Leishmania (Leishmania) infantum chagasi-infected hamsters. Golden Syrian hamsters infected with L. (L.) infantum chagasi were treated with either miltefosine (46 mg/kg) or allopurinol (460 mg/kg) alone by oral route or associated with rldccys1 (150 µg/hamster) by subcutaneous route for 30 days. Infected hamsters were also treated with miltefosine (46 mg/kg) plus rldccys1 (150 µg/hamster) for 30 days (phase 1) followed by two additional doses of rldccys1 (250 µg/hamster) (phase 2). After the end of treatment, the animals were analyzed for parasite load, body weight, serum levels of immunoglobulins, cytokine expression, and drug toxicity. The data showed a significant decrease of parasite load in infected hamsters treated with allopurinol or miltefosine alone or associated with rldccys1, as well as in those treated with rldccys1 alone. Significantly lower levels of serum IgG were detected in hamsters treated with allopurinol plus rldccys1. The treatment with miltefosine associated with rldccys1 prevented relapse observed in animals treated with miltefosine alone. A significant loss of body weight was detected only in some hamsters treated with miltefosine for 1 month and deprived of this treatment for 15 days. There were no significant differences in transcript expression of IFN-γ and IL-10 in any of treated groups. Neither hepatotoxicity nor nephrotoxicity was observed among controls and treated groups. These findings open perspectives to further explore this immunochemotherapeutic schedule as an alternative for treatment of visceral leishmaniasis.

Human tumor necrosis factor alpha affects the egg-laying dynamics and glucose metabolism of Schistosoma mansoni adult worms in vitro.

Several studies have described the effects of human tumor necrosis factor alpha (hTNF-α) on Schistosoma mansoni. hTNF-α affects the worm's development, metabolism, egg-laying, gene expression and protein phosphorylation. The available data on the influence of hTNF-α on egg-laying in S. mansoni are controversial, but understanding the mechanism of egg-laying regulation in this species is essential in combating schistosomiasis. We characterized the effects of in vitro treatment of S. mansoni adult worms with different doses of hTNF-α (5, 20 and 40 ng/ml) for 5 days. We explored the effects on egg-laying rate, glucose levels, ATP metabolism, and messenger RNA (mRNA) expression levels of lactate dehydrogenase, glucose transporters and the parasite gene which acts as an hTNF-α receptor, SmTNFR. hTNF-α influenced egg-laying in a time- and dose-dependent manner: at a dose of 40 ng/ml, egg-laying increased on day 2 and decreased on days 3 and 4; at 20 ng/ml, egg-laying decreased on day 3; while at 5 ng/ml, egg-laying decreased on day 4. The total number of eggs produced was not affected by the different treatments, but the egg-laying dynamics were: the median egg-laying time decreased significantly with treatment, and egg developmental stages and size were also affected. At 5 and 20 ng/ml hTNF-α, lactate production diminished on day 3 up to day 5, while glucose uptake increased on day 5. At 40 ng/ml, glucose uptake diminished on day 1 up to day 3, while ATP accumulation was detected on day 5. No significant changes in mRNA expression were detected in any of the treatments. We found that crosstalk involving hTNF-α and parasite signaling plays a role in the fine-scale regulation of the worm's metabolism and physiology, and points to new strategies for disease control.

Increased levels of TAR DNA-binding protein 43 in the hippocampus of subjects with bipolar disorder: a postmortem study.

Bipolar disorder shares symptoms and pathological pathways with other neurodegenerative diseases, including frontotemporal dementia (FTD). Since TAR DNA-binding protein 43 (TDP-43) is a neuropathological marker of frontotemporal dementia and it is involved in synaptic transmission, we explored the role of TDP-43 as a molecular feature of bipolar disorder (BD). Homogenates were acquired from frozen hippocampus of postmortem brains of bipolar disorder subjects. TDP-43 levels were quantified using an ELISA-sandwich method and compared between the postmortem brains of bipolar disorder subjects and age-matched control group. We found higher levels of TDP-43 protein in the hippocampus of BD (n = 15) subjects, when compared to controls (n = 15). We did not find associations of TDP-43 with age at death, postmortem interval, or age of disease onset. Our results suggest that protein TDP-43 may be potentially implicated in behavioral abnormalities seen in BD. Further investigation is needed to validate these findings and to examine the role of this protein during the disease course and mood states.

Brain areas involved with obsessive-compulsive disorder present different DNA methylation modulation.

BACKGROUND: Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive actions, that presents the involvement of the cortico-striatal areas. The contribution of environmental risk factors to OCD development suggests that epigenetic mechanisms may contribute to its pathophysiology. DNA methylation changes and gene expression were evaluated in post-mortem brain tissues of the cortical (anterior cingulate gyrus and orbitofrontal cortex) and ventral striatum (nucleus accumbens, caudate nucleus and putamen) areas from eight OCD patients and eight matched controls. RESULTS: There were no differentially methylated CpG (cytosine-phosphate-guanine) sites (DMSs) in any brain area, nevertheless gene modules generated from CpG sites and protein-protein-interaction (PPI) showed enriched gene modules for all brain areas between OCD cases and controls. All brain areas but nucleus accumbens presented a predominantly hypomethylation pattern for the differentially methylated regions (DMRs). Although there were common transcriptional factors that targeted these DMRs, their targeted differentially expressed genes were different among all brain areas. The protein-protein interaction network based on methylation and gene expression data reported that all brain areas were enriched for G-protein signaling pathway, immune response, apoptosis and synapse biological processes but each brain area also presented enrichment of specific signaling pathways. Finally, OCD patients and controls did not present significant DNA methylation age differences. CONCLUSIONS: DNA methylation changes in brain areas involved with OCD, especially those involved with genes related to synaptic plasticity and the immune system could mediate the action of genetic and environmental factors associated with OCD.

Are the 50's, the transition decade, in choroid plexus aging?

The choroid plexus (CP) is an important structure for the brain. Besides its major role in the production of cerebrospinal fluid (CSF), it conveys signals originating from the brain, and from the circulatory system, shaping brain function in health and in pathology. Previous studies in rodents have revealed altered transcriptome both during aging and in various diseases of the central nervous system, including Alzheimer's disease. In the present study, a high-throughput sequencing of the CP transcriptome was performed in postmortem samples of clinically healthy individuals aged 50's through 80's. The data shows an age-related profile, with the main changes occurring in the transition from the 50's to the 60's, stabilizing thereafter. Specifically, neuronal and membrane functions distinguish the transcriptome between the 50's and the 60's, while neuronal and axon development and extracellular structure organization differentiate the 50's from the 70's. These findings suggest that changes in the CP transcriptome occur early in the aging process. Future studies will unravel whether these relate with processes occurring in late- onset brain diseases.

Neuropsychiatric Inventory in Community-Dwelling Older Adults with Mild Cognitive Impairment and Dementia.

BACKGROUND: Behavioral and psychological symptoms (BPSD) can be a prodrome of dementia, and the Neuropsychiatric Inventory (NPI) is widely used for BPSD evaluation. OBJECTIVE: To compare the prevalence of BPSD according to cognitive status, and to determine NPI cutoffs that best discern individuals with mild cognitive impairment (MCI) and dementia from those without dementia. METHODS: We included 1,565 participants (mean age = 72.7±12.2 years, 48% male). BPSD and cognitive status were assessed with the NPI and the Clinical Dementia Rating (CDR). We used multivariable logistic regression models to investigate the association of BPSD with cognitive status. The area under the curve (AUC) was used to assess model discrimination, and to determine the best NPI cutoff for MCI and dementia. RESULTS: Participants were cognitively normal (CDR = 0; n = 1,062), MCI (CDR = 0.5; n = 145), or dementia (CDR≥1.0, n = 358). NPI symptoms were more frequent in dementia and MCI when compared to cognitively normal. Higher odds for delusions, hallucinations, disinhibition, and psychomotor alterations were found among participants with dementia and MCI than in those who were cognitively normal. The best NPI cutoff to discern participants with dementia from those cognitively normal was 11 (AUC = 0.755). Poor discrimination (AUC = 0.563) was found for the comparison of MCI and those cognitively normal. CONCLUSIONS: We found an increase in BPSD frequencies across the continuum of cognitive impairment. BPSD severity and frequency in MCI was more similar to individuals cognitively normal than with dementia. NPI scores≥to 11 in individuals with no diagnosis of dementia can support the decision for further investigation of dementia.

Layer-specific reduced neuronal density in the orbitofrontal cortex of older adults with obsessive-compulsive disorder.

Neurobiological models have provided consistent evidence of the involvement of cortical-subcortical circuitry in obsessive-compulsive disorder (OCD). The orbitofrontal cortex (OFC), involved in motivation and emotional responses, is an important regulatory node within this circuitry. However, OFC abnormalities at the cellular level have so far not been studied. To address this question, we have recruited a total of seven senior individuals from the Sao Paulo Autopsy Services who were diagnosed with OCD after an extensive post-mortem clinical evaluation with their next of kin. Patients with cognitive impairment were excluded. The OCD cases were age- and sex-matched with 7 control cases and a total of 14 formalin-fixed, serially cut, and gallocyanin-stained hemispheres (7 subjects with OCD and 7 controls) were analyzed stereologically. We estimated laminar neuronal density, volume of the anteromedial (AM), medial orbitofrontal (MO), and anterolateral (AL) areas of the OFC. We found statistically significant layer- and region-specific lower neuron densities in our OCD cases that added to a deficit of 25% in AM and AL and to a deficit of 21% in MO, respectively. The volumes of the OFC areas were similar between the OCD and control groups. These results provide evidence of complex layer and region-specific neuronal deficits/loss in old OCD cases which could have a considerable impact on information processing within orbitofrontal regions and with afferent and efferent targets.

Extracellular vesicles isolated from Toxoplasma gondii induce host immune response.

This study established a protocol to purify Toxoplasma gondii tachyzoite microvesicles and exosomes, called as extracellular vesicles (EVs). In addition, the investigations were conducted to determine the kinetic of EV release by tachyzoites and whether EV proteins are able to modulate the host immune response. The particle size and concentration released by tachyzoites in culture medium at different incubation-period were characterized by nanoparticle tracking analysis. Tachyzoites (1 × 106 ) released around 4.37 ± 0.81 × 108 EVs/mL/h, with size varying between 138.2 and 171.9 nm. EVs released into the medium were purified by gel-exclusion chromatography and screened by ELISA, using a pool of human positive sera for toxoplasmosis. EV-fractions contained high concentration of proteins, and EVs were analyzed by scanning and transmission electron microscopies. Tachyzoites released EVs into the culture medium throughout all membrane surface, and these vesicles contain small RNAs/miRNA. Pooled sera from chronically infected human or mice (infected with 2 different T. gondii strains) recognized distinct EV electrophoretic patterns in immunoblotting. T. gondii EVs significantly induced IL-10, TNF-α and iNOS in murine macrophages. In conclusion, this study shows that T. gondii secrete/excrete EVs (microvesicles and exosomes) contain miRNA and they were immunologically recognized by host immune response.

Factors associated with brain volume in major depression in older adults without dementia: results from a large autopsy study.

OBJECTIVE: We examined brain volume and atrophy in individuals with major depressive disorder (MDD) without dementia that were referred to a large autopsy service. We also examined potential risk factors for brain atrophy, including demographics and clinical variables. METHODS: In this study, 1373 participants (787 male) aged 50 years or older who died from natural causes were included. Participants with no reliable informant, with cognitive impairment or dementia, with a medical history of severe chronic disease, or with prolonged agonal state were excluded. Presence of MDD at least once in their lifetime was defined according to the Structured Clinical Interview for DSM. Brain volume was measured immediately after removal from the skull. RESULTS: Mean age at death was 68.6 ± 11.6, and MDD was present in 185 (14%) individuals. Smaller brain volume was associated with older age (p < 0.001), lower education (years; p < 0.001), hypertension (p = 0.001), diabetes (p = 0.006), and female gender (p < 0.001). In the multivariate analysis adjusted for sociodemographics and cardiovascular risk factors, smaller brain volume was not associated with major depression (ß = -0.86, 95% CI = -26.50 to 24.77, p = 0.95). CONCLUSIONS: In this large autopsy study of older adults, MDD was not associated with smaller brain volumes. Regardless of the presence of MDD, in this sample of older adults without dementia, we found that smaller brain volumes were associated with risk factors for brain neurodegeneration such as older age, diabetes, hypertension, and lower education. Copyright © 2017 John Wiley & Sons, Ltd.

Three-dimensional and stereological characterization of the human substantia nigra during aging.

The human brain undergoes non-uniform changes during aging. The substantia nigra (SN), the source of major dopaminergic pathways in the brain, is particularly vulnerable to changes in the progression of several age-related neurodegenerative diseases. To establish normative data for high-resolution imaging, and to further clinical and anatomical studies we analyzed SNs from 15 subjects aged 50-91 cognitively normal human subjects without signs of parkinsonism. Complete brains or brainstems with substantia nigra were formalin-fixed, celloidin-mounted, serially cut and Nissl-stained. The shapes of all SNs investigated were reconstructed using fast, high-resolution computer-assisted 3D reconstruction software. We found a negative correlation between age and SN volume (p = 0.04, rho = -0.53), with great variability in neuronal numbers and density across participants. The 3D reconstructions revealed SN inter- and intra-individual variability. Furthermore, we observed that human SN is a neuronal reticulum, rather than a group of isolated neuronal islands. Caution is required when using SN volume as a surrogate for SN status in individual subjects. The use of multimodal sequences including those for fiber tracts may enhance the value of imaging as a diagnostic tool to assess SN in vivo. Further studies with a larger sample size are needed for understanding the structure-function interaction of human SN.

Avaliação da assistência pré-natal: relevância dos exames laboratoriais / Evaluation of prenatal care: relevance of laboratory examinations / Evaluación de la asistencia prenatal: relevancia de las pruebas

Objetivo: Avaliar a assistência pré-natal de mulheres assistidas ao parto e verificar a relevância dos exames laboratoriais na qualidade do pré-natal. Métodos: Estudo de corte transversal desenvolvido em um hospital universitário de referência na cidade de Santa Cruz- RN, no período de junho a julho de 2014, com 50 parturientes assistidas ao parto. As mulheres tinham entre 18-40 anos e possuíam baixo risco obstétrico. Os dados foram coletados a partir do cartão do pré-natal e aplicação de questionário estruturado. A caracterização da adequação do pré-natal foi elaborada com base nas diretrizes do Programa de Humanização do Pré-natal e Puerpério (PHPN) e no Manual Técnico de Pré-natal e Puerpério (MTPP).Realizou-se análise descritiva dos dados e o teste Qui-quadrado para a verificação de diferenças entre as proporções. Resultados: Observou-se que 86% (n=43) iniciaram o pré-natal precocemente e obtiveram uma média de 7,3 consultas. Os procedimentos clínicos obstétricos tiveram cinco ou mais registros em 58% (n=29) da amostra. Quando avaliado o registro de exames laboratoriais, observou-se um baixo percentual de adequação na 2ª rotina de exame preconizada (32%, n=16). De acordo com os parâmetros (PHPN e MTPP), o pré-natal esteve adequado apenas em 24% (n=12) dos casos. Quando avaliada a classificação da assistência do pré-natal sem o uso dos exames laboratoriais, a adequação subiu para 48% (n=24), com diferença estatisticamente significantes (p<0,001). Conclusão: O acesso ao pré-natal foi satisfatório, entretanto, a qualidade do pré-natal foi deficiente e a maior fragilidade parece estar relacionada aos registros dos exames laboratoriais.

Objective: To evaluate the prenatal care assistance provided to women assisted at delivery and examine the relevance of laboratory tests on the quality of prenatal care. Methods: A cross-sectional cohort study carried out in a university referral hospital, in the city of Santa Cruz-RN, from June to July 2014, including 50 pregnant women assisted at delivery. The women were between 18-40 years old and presented low obstetric risk. Data was collected from the prenatal medical chart and through a structured questionnaire. The characterization of the prenatal assistance adequacy was developed based on guidelines of the Prenatal and Puerperium Humanization Program (PPHP) and the Prenatal and Postpartum Technical Manual (PPTM). A descriptive analysis of the data was performed and the chi-square test was used for verification of differences between proportions. Results: It was observed that 86% (n=43) of the women initiated the prenatal care assistance early and had an average of 7.3 appointments. The clinical obstetric procedures had five or more records in 58% (n=29) of the sample. When assessed the laboratory tests records, a low percentage of adequacy was found in the 2nd recommended routine testing (32%, n=16). According to the parameters (PPHP and PPTM), prenatal care was suitable only in 24% (n=12) of the cases. When evaluated the classification of prenatal care assistance without the use of laboratory tests, the adequacy rose to 48% (n=24), presenting a statistically significant difference (p<0.001). Conclusion: Access to prenatal care assistance was satisfactory; however, its quality was deficient, and the major weakness seems to be related to the records of laboratory tests.

Objetivo: Evaluar la asistencia prenatal de mujeres asistidas en el parto y verificar la relevancia de las pruebas de laboratorio para la calidad del prenatal. Métodos: Estudio transversal desarrollado em un hospital universitario de referencia de la ciudad de Santa Cruz-RN en el período entre junio y julio de 2014 con 50 parturientas asistidas en el parto. Las mujeres tenían entre 18-40 años y riesgo obstétrico bajo. Fueron recogidos los datos de la tarjeta del prenatal y aplicación de un cuestionario estructurado. La caracterización de la adecuación del prenatal fue elaborada basado en las directrices del Programa de Humanización del Prenatal y Puerperio (PHPN) y em el Manual Técnico del Prenatal y Puerperio (MTPP). Se realizó um análisis descriptivo de los datos y el test Chi-cuadrado para verificar las diferencias de las proporciones. Resultados: Se observó que el 86% (n=43) iniciaron el prenatal precoz y tuvieron una media de 7,3 consultas. Los procedimientos clínicos de la obstetrícia tuvieron cinco o más registros en el 58% (n=29) de la muestra. En la evaluación del registro de las pruebas de laboratorio se observó un porcentual de adecuación bajo en la 2ª rutina de prueba establecida (32%, n=16). Según los parámetros (PHPN y MTPP), el prenatal fue adecuado solamente para el 24% (n=12) de los casos. En la evaluación de la clasificación de la asistencia del prenatal sin el uso de pruebas de laboratorio, la adecuación subió al 48% (n=24) con diferencia estadística significativa (p<0,001). Conclusión: El acceso al prenatal fue satisfactorio, sin embargo, la calidad del prenatal fue deficiente y la mayor fragilidad parece relacionarse com los registros de las pruebas de laboratorio.

Efeito da cinesioterapia na qualidade de vida, função sexual e sintomas climatéricos em mulheres com fibromialgia / Kinesiotherapy effect on quality of life, sexual function and climacteric symptoms in women with fibromyalgia

Objetivo: Avaliar e comparar o efeito da cinesioterapia na qualidade de vida, função sexual e sintomas climatéricos em mulheres climatéricas com e sem fibromialgia. Métodos: Participaram 90 mulheres climatéricas, divididas em dois grupos: fibromialgia (47) e controle (43). As pacientes foram avaliadas nas variáveis: qualidade de vida (Utian Quality of Life [UQOL]), função sexual (questionário do quociente sexual/versão feminina [QS-F]) e intensidade dos sintomas climatérios (Índice Menopausal de Blatt-Kupperman [IMBK]). Os grupos fizeram cinesioterapia para o assoalho pélvico, composto de 20 sessões, duas vezes por semana. Análise estatística foi feita por meio dos testes t de Student pareado, análise de variância de delineamento misto e Kappa de Cohen. Resultados: Na qualidade de vida, foi observada melhoria em ambos os grupos para todos os domínios avaliados. Na análise intergrupo foi evidenciada diferença nos domínios emocional (p = 0,01), saúde (0,03) e sexual (p = 0,001) com ganhos mais expressivos para o grupo controle. Na função sexual, foi verificada melhoria nos grupos, após a intervenção; na análise intergrupo as fibromiálgicas apresentaram escores inferiores ao grupo controle (p < 0,001). Em relação aos sintomas climatéricos não houve diferença na análise intergrupo pós-intervenção (p = 0,73). Entretanto, ambos os grupos apresentaram redução significativa da sintomatologia após a intervenção (p < 0,001). Conclusões: A cinesioterapia do assoalho pélvico exerce efeito benéfico sobre os domínios da qualidade de vida, função sexual e sintomatologia climatérica em mulheres com e sem fibromialgia na fase do climatério. Entretanto, a fibromialgia parece ser fator limitante para melhores resultados em alguns aspectos avaliados .

Objective: To evaluate the effect of the kinesiotherapy in the quality of life, sexual function and menopause-related symptoms and compare in climacteric women with and without fibromyalgia (FM). Methodology: The group was composed of 90 climacteric women divided in 2 groups: FM (47) and control (43). The patients were analyzed on their quality of life (Utian Quality of Life [UQoL]), sexual function (Sexual Quotient-Female Version [SQ-F] questionnaire) and intensity of the climacteric symptoms (Blatt–Kupperman menopausal index [BKMI]). Both groups performed pelvic floor kinesiotherapy, composed of 20 sessions, twice a week. Statistical analysis was performed using Student's t-test, mixed-design analysis of variance (ANOVA) and Cohen's Kappa. Results: In the quality of life, an improvement was noticed in both groups for all domains analyzed. In the comparison between groups it was noticed a difference in the emotional (p = 0.01), health (p = 0.03) and sexual (p = 0.001) domains with considerable gains verified in the control group. Improvement was also noticed in the sexual function. In the analysis between groups, FM group showed a lower score compared to the control group (p < 0.001). With respect to the climacteric symptoms, there was no difference in the analysis between groups after the intervention (p < 0.001). Conclusions: The pelvic floor kinesiotherapy promotes a positive effect in the domains of quality of life, sexual function and climacteric symptoms in women with and without fibromyalgia in the climacteric period; however, fibromyalgia seems to be a limiting factor to achieve better results in some of the aspects evaluated. .

[Kinesiotherapy effect on quality of life, sexual function and climacteric symptoms in women with fibromyalgia]. / Efeito da cinesioterapia na qualidade de vida, função sexual e sintomas climatéricos em mulheres com fibromialgia.

OBJECTIVE: To evaluate the effect of the kinesiotherapy in the quality of life, sexual function and menopause-related symptoms and compare in climacteric women with and without fibromyalgia (FM). METHODOLOGY: the group was composed of 90 climacteric women divided in 2 groups: FM (47) and control (43). The patients were analyzed on their quality of life (Utian Quality of Life [UQoL]), sexual function (Sexual Quotient-Female Version [SQ-F] questionnaire) and intensity of the climacteric symptoms (Blatt-Kupperman menopausal index [BKMI]). Both groups performed pelvic floor kinesiotherapy, composed of 20 sessions, twice a week. Statistical analysis was performed using Student's t-test, mixed-design analysis of variance (ANOVA) and Cohen's Kappa. RESULTS: In the quality of life, an improvement was noticed in both groups for all domains analyzed. In the comparison between groups it was noticed a difference in the emotional (p=0.01), health (p=0.03) and sexual (p=0.001) domains with considerable gains verified in the control group. Improvement was also noticed in the sexual function. In the analysis between groups, FM group showed a lower score compared to the control group (p < 0.001). With respect to the climacteric symptoms, there was no difference in the analysis between groups after the intervention (p < 0.001). CONCLUSIONS: The pelvic floor kinesiotherapy promotes a positive effect in the domains of quality of life, sexual function and climacteric symptoms in women with and without fibromyalgia in the climacteric period; however, fibromyalgia seems to be a limiting factor to achieve better results in some of the aspects evaluated.

[SUS management and monitoring and evaluation practices: possibilities and challenges for building a strategic agenda]. / A gestão do SUS e as práticas de monitoramento e avaliação: possibilidades e desafios para a construção de uma agenda estratégica.

This paper deals with the challenges involved in institutionalizing Monitoring and Evaluation practices within the scope of management of the Brazilian Unified Health System (SUS), based on the creation of a strategic agenda. This is structured around actions by the Federal Administration, from the perspective of defining the scope of the federative relationship. A summarized literature review is thus presented, placing into context the current SUS management process, which is based on the Pact for Health as well as theoretical and operational aspects inherent to monitoring and evaluation practices. The approach related to the strategic agenda highlights the creation of mechanisms that underpin the political and institutional decision, namely the creation of financial incentives and the development of technical mechanisms. These include organizational strategies for qualifying management teams and conducting studies and research and the dissemination of strategic information. These processes are based on the concept of providing for the management specificities in the different spheres of management based on a broad cooperation process involving teaching and research institutions and international organizations as well as the managers themselves.

A gestão do SUS e as práticas de monitoramento e avaliação: possibilidades e desafios para a construção de uma agenda estratégica / SUS management and monitoring and evaluation practices: possibilities and challenges for building a strategic agenda

O presente artigo trata dos desafios de se institucionalizar as práticas de Monitoramento e Avaliação no âmbito da Gestão do Sistema Único de Saúde, tendo como base a construção de uma agenda estratégica, organizada a partir das ações do Gestor Federal, na perspectiva de qualificar o espaço da relação federativa. Para tanto é apresentada uma revisão sumária da literatura, contextualizando o atual processo da gestão do SUS, que tem como base o Pacto pela Saúde, como também aspectos teóricos e operacionais inerentes às práticas do monitoramento e avaliação. A abordagem relacionada à agenda estratégica destaca a criação de mecanismos que articulam a decisão político-institucional, a criação de incentivos financeiros, o desenvolvimento de mecanismos técnicos; estratégias organizacionais de qualificação das equipes gestores; a realização de estudos e pesquisa e a divulgação de informações estratégicas, processos estes pautados pela concepção de atender as especificidades da gestão nas suas diferentes esferas e tendo como base um amplo processo de cooperação envolvendo, além dos gestores, as instituições de ensino e pesquisa e as organizações internacionais.

This paper deals with the challenges involved in institutionalizing Monitoring and Evaluation practices within the scope of management of the Brazilian Unified Health System (SUS), based on the creation of a strategic agenda. This is structured around actions by the Federal Administration, from the perspective of defining the scope of the federative relationship. A summarized literature review is thus presented, placing into context the current SUS management process, which is based on the Pact for Health as well as theoretical and operational aspects inherent to monitoring and evaluation practices. The approach related to the strategic agenda highlights the creation of mechanisms that underpin the political and institutional decision, namely the creation of financial incentives and the development of technical mechanisms. These include organizational strategies for qualifying management teams and conducting studies and research and the dissemination of strategic information. These processes are based on the concept of providing for the management specificities in the different spheres of management based on a broad cooperation process involving teaching and research institutions and international organizations as well as the managers themselves.

Association between cardiovasculardisease and dementia / Associação entre doença cardiovascular e demência

Abstract ­ Longitudinal studies have shown association between cardiovascular risk factors and dementia. However, these studies are not capable of detecting asymptomatic cardiovascular alterations and thus may provide erroneous estimates of association. Autopsy studies could be more useful in elucidating these questions. The present clinicopathological study sought to examine the relationship between dementia, cardiovascular risk factors and disease. Methods: 603 subjects, who underwent autopsy, were classified regarding the presence of dementia, according to post mortem cognitive classification. Demographics, cardiovascular risk factors, and anatomically-proven cardiovascular disease (myocardial hypertrophy, cerebral and carotid atherosclerosis) were compared among cognitively normal persons and individuals with dementia. Results: Cognitive deficit was associated with advanced age, stroke, physical inactivity and low body mass index (p<0.05). Circle of Willis atherosclerosis was greater in patients with dementia than in controls on univariate analysis (p=0.01). However, this association lost significance when adjusted by age and gender (p=0.61). Heart failure and anatomopathological cardiac parameters were more severe in the control group than in demented individuals (p<0.05). Carotid artery atherosclerosis and intima-media thickness were similar in both groups. Conclusion: Advanced age, stroke, physical inactivity and low body mass index were linked to dementia. Circle of Willis atherosclerosis was associated with dementia only when age was not considered. Our results suggest that cerebral artery atherosclerosis was not directly associated with clinical expression of dementia.

Resumo ­ Estudos longitudinais tem mostrado associação entre fatores de risco cardiovascular e demência. Entretanto, estes estudos não são capazes de detectar alterações cardiovasculares assintomáticas e podem, assim, fornecer estimativas de associação errôneas. Estudos de autópsia podem ser mais úteis em elucidar estas questões. O presente estudo clinicopatológico busca examinar a relação entre demência, fatores e doença cardiovascular. Métodos: 603 sujeitos submetidos à autópsia foram classificados quanto à presença de demência, usando uma classificação cognitiva post-mortem. Dados demográficos, fatores de risco cardiovascular e doença cardiovascular comprovada anatomicamente (hipertrofia miocárdica, aterosclerose cerebral e carotídea) foram comparados entre indivíduos cognitivamente normais e com demência. Resultados: Déficit cognitivo esteve associado à idade avançada, acidente vascular cerebral, sedentarismo e baixo índice de massa corpórea (p<0,05). Aterosclerose do polígono de Willis foi maior em pacientes com demência do que em controles na análise univariada (p=0,01). Insuficiência cardíaca e parâmetros anatomopatológicos cardíacos foram mais graves entre o grupo controle que entre os indivíduos dementados (p<0,05). Aterosclerose de artérias carótidas e espessura íntima-média foram similares entre os grupos. Conclusão: Idade avançada, acidente vascular cerebral, sedentarismo e baixo índice de massa corpórea estiveram relacionados à demência. Aterosclerose de polígono de Willis esteve associada à demência, somente quando a idade não foi considerada. Nossos resultados sugerem que a aterosclerose de artérias cerebrais não está diretamente relacionada com a expressão clínica de demência.

O pacto pela saúde e os desafios para a implementação política de gestão estratégica e participativa / Pacto pela saúde and the challenges for establishing a strategic and participative management

A integração dos processos de implementação do Pacto pela Saúde e da Política Nacional de Gestão Estratégica e Participativa é um desafio que vem sendo enfrentado pelo Ministério da Saúde, através das ações e práticas da Secretária da Gestão Estratégica e Participativa, tendo como pontos centrais a valorização dos diferentes mecanismos de participação popular e de controle social, a integração e interação das ações de auditoria, ouvidoria, monitoramento e avaliação da gestão do Sistema Único de Saúde (SUS) com o controle social. O presente texto retrata a situação atual da implementação da PolíticaSUS e do Pacto pela saúde, contribuindo com um processo de cooperação intergestores, com base pela saúde, contribuindo com um processo de cooperação intergestores, com base nas necessidades de gestão apontadas.

The integration between Pacto pela saúde and the National Policy of Strategic and Participative Management in the National Health System is a challenge for the Ministry of Health, trough the actions and practices of Strategic and Participative Management Secretariat, which values the different mechanisms of social control and popular participation in the system management and also the interaction between Auditing, Participative Management, Monitoring and Evaluation of Management System and Ombuds Agency. The text shows the actual moment of the political issues of the National Policy of Strategic and Participative Management in the National Health System and Pacto pela saúde, with the objective of contributing in a co-operation process to political managers.

Association between cardiovascular disease and dementia.

Longitudinal studies have shown association between cardiovascular risk factors and dementia. However, these studies are not capable of detecting asymptomatic cardiovascular alterations and thus may provide erroneous estimates of association. Autopsy studies could be more useful in elucidating these questions. The present clinicopathological study sought to examine the relationship between dementia, cardiovascular risk factors and disease. METHODS: 603 subjects, who underwent autopsy, were classified regarding the presence of dementia, according to post mortem cognitive classification. Demographics, cardiovascular risk factors, and anatomically-proven cardiovascular disease (myocardial hypertrophy, cerebral and carotid atherosclerosis) were compared among cognitively normal persons and individuals with dementia. RESULTS: Cognitive deficit was associated with advanced age, stroke, physical inactivity and low body mass index (p< 0.05). Circle of Willis atherosclerosis was greater in patients with dementia than in controls on univariate analysis (p=0.01). However, this association lost significance when adjusted by age and gender (p=0.61). Heart failure and anatomopathological cardiac parameters were more severe in the control group than in demented individuals (p< 0.05). Carotid artery atherosclerosis and intima-media thickness were similar in both groups. CONCLUSION: Advanced age, stroke, physical inactivity and low body mass index were linked to dementia. Circle of Willis atherosclerosis was associated with dementia only when age was not considered. Our results suggest that cerebral artery atherosclerosis was not directly associated with clinical expression of dementia.

Estudos longitudinais tem mostrado associação entre fatores de risco cardiovascular e demência. Entretanto, estes estudos não são capazes de detectar alterações cardiovasculares assintomáticas e podem, assim, fornecer estimativas de associação errôneas. Estudos de autópsia podem ser mais úteis em elucidar estas questões. O presente estudo clinicopatológico busca examinar a relação entre demência, fatores e doença cardiovascular. MÉTODOS: 603 sujeitos submetidos à autópsia foram classificados quanto à presença de demência, usando uma classificação cognitiva post-mortem. Dados demográficos, fatores de risco cardiovascular e doença cardiovascular comprovada anatomicamente (hipertrofia miocárdica, aterosclerose cerebral e carotídea) foram comparados entre indivíduos cognitivamente normais e com demência. RESULTADOS: Déficit cognitivo esteve associado à idade avançada, acidente vascular cerebral, sedentarismo e baixo índice de massa corpórea (p< 0,05). Aterosclerose do polígono de Willis foi maior em pacientes com demência do que em controles na análise univariada (p=0,01). Insuficiência cardíaca e parâmetros anatomopatológicos cardíacos foram mais graves entre o grupo controle que entre os indivíduos dementados (p< 0,05). Aterosclerose de artérias carótidas e espessura íntima-média foram similares entre os grupos. CONCLUSÃO: Idade avançada, acidente vascular cerebral, sedentarismo e baixo índice de massa corpórea estiveram relacionados à demência. Aterosclerose de polígono de Willis esteve associada à demência, somente quando a idade não foi considerada. Nossos resultados sugerem que a aterosclerose de artérias cerebrais não está diretamente relacionada com a expressão clínica de demência.

Transcription profiling of signal transduction-related genes in sugarcane tissues.

A collection of 237,954 sugarcane ESTs was examined in search of signal transduction genes. Over 3500 components involved in several aspects of signal transduction, transcription, development, cell cycle, stress responses and pathogen interaction were compiled into the Sugarcane Signal Transduction (SUCAST) Catalogue. Sequence comparisons and protein domain analysis revealed 477 receptors, 510 protein kinases, 107 protein phosphatases, 75 small GTPases, 17 G-proteins, 114 calcium and inositol metabolism proteins, and over 600 transcription factors. The elements were distributed into 29 main categories subdivided into 409 sub-categories. Genes with no matches in the public databases and of unknown function were also catalogued. A cDNA microarray was constructed to profile individual variation of plants cultivated in the field and transcript abundance in six plant organs (flowers, roots, leaves, lateral buds, and 1st and 4th internodes). From 1280 distinct elements analyzed, 217 (17%) presented differential expression in two biological samples of at least one of the tissues tested. A total of 153 genes (12%) presented highly similar expression levels in all tissues. A virtual profile matrix was constructed and the expression profiles were validated by real-time PCR. The expression data presented can aid in assigning function for the sugarcane genes and be useful for promoter characterization of this and other economically important grasses.

The sugarcane signal transduction (SUCAST) catalogue: prospecting signal transduction in sugarcane

O sequenciamento de ESTs (etiquetas de seqüências transcritas) tem possibilitado a descoberta de muitos novos genes em uma ampla variedade de organismos. Um aumento do aproveitamento desta informaçäo pela comunidade científica tem sido possível graças ao desenvolvimento de base de dados contendo seqüências completamente anotadas. O trabalho aqui relatado teve como objetivo a identiflcaçäo de ESTs de cana de açúcar seqüenciadas através do projeto SUCEST (http://sucest.lad.ic.unicamp.br) que codificam para proteínas envolvidas em mecanismos de transduçäo de sinal. Nós também preparamos um catálogo dos componentes de transduçäo de sinal da cana de açúcar (SUCAST) englobando as principais categorias e vias conhecidas (http://sucest.lad.ic.unicamp.br/private/mining-reports/QG/QG-mining.htm). ESTs codificadoras de enzimas envolvidas nas rotas de biossíntese de hormônios (giberelinas, etileno, auxinas, ácido abscíssico, ácido jasmônico) foram encontradas e sua expressäo específica nos tecidos foi inferida a partir de seu enriquecimento nas diferentes bibliotecas. Quando possível, transmissores do sinal hormonal e da resposta a peptídeos produzidos pela planta foram associados a suas respectivas vias. Mais de 100 receptores foram encontrados na cana de açúcar, entre os quais uma grande família de receptores Ser/Thr quinase e também de fotoreceptores, receptores do tipo histidina quinase e seus respectivos reguladores da resposta. Proteínas G e GTPases pequenas foram também analisadas e comparadas com membros destas famílias já conhecidos em mamíferos e plantas. As vias principais que envolvem a participaçäo de proteínas quinases e fosfatases foram mapeadas, em especial as vias da quinase MAP quinase e do inositol que säo bem estudadas em plantas.