Host Genetics Background Influence in the Intragastric Trypanosoma cruzi Infection.

Background: Considering the complexity of the factors involved in the immunopathology of Chagas disease, which influence the Chagas' disease pathogenesis, anti-T. cruzi immune response, and chemotherapy outcome, further studies are needed to improve our understanding about these relationships. On this way, in this article we analyzed the host genetic influence on hematological, histopathological and immunological aspects after T. cruzi infection. Methods: BALB/c and A mice were intragastrically infected with T. cruzi SC2005 strain, isolated from a patient of an outbreak of Chagas disease. Parameters such as parasite load, survival rates, cytokines production, macrophages, T and B cell frequencies, and histopathology analysis were carried out. Results: BALB/c mice presented higher parasitemia and mortality rates than A mice. Both mouse lineages exhibited hematological alterations suggestive of microcytic hypochromic anemia and histopathological alterations in stomach, heart and liver. The increase of CD8+ T cells, in heart, liver and blood, and the increase of CD19+ B cells, in liver, associated with a high level of proinflammatory cytokines (IL-6, TNF-α, IFN-γ), confer a resistance profile to the host. Although BALB/c animals exhibited the same findings observed in A mice, the response to infection occurred later, after a considerable parasitemia increase. By developing an early response to the infection, A mice were found to be less susceptible to T. cruzi SC2005 infection. Conclusions: Host genetics background shaping the response to infection. The early development of a cytotoxic cellular response profile with the production of proinflammatory cytokines is important to lead a less severe manifestation of Chagas disease.

Financial impact of the change in the vulnerability profile of More Doctors Program.

OBJECTIVE: To estimate the flow of professionals and the financial impact of the Programa Mais Médicos para o Brasil (PMMB - More Doctors for Brazil Program) within the More Doctors Program (MDP) for the Brazilian Ministry of Health and the participating municipalities of the state of São Paulo, from January 2019 to March 2022. METHODS: A financial impact study was conducted in the state of São Paulo based on public secondary databases. The number of PMMB vacancies per municipality, of physicians and vulnerability profiles were described to measure the loss of replacement of professionals in the period. RESULTS: In the specified period, the number of PMMB physicians in participating cities will decrease from 2,533 to 320, and the number of participating municipalities from 373 to 86. The municipalities that will need to replace the physicians will have a financial impact of R$ 929,487,904.77 (with sensitivity analysis, ranging from R$ 650,641,533.34 to R$ 1,208,334,276.20). CONCLUSION: The change of vulnerability methodology adopted for the PMMB will represent serious consequences, that is, less population assistance and high financial impact for the municipalities of the state of São Paulo in a scenario of budget limitations.

Financial impact of the change in the vulnerability profile of More Doctors Program / Impacto financeiro da alteração do perfil de vulnerabilidade no Programa Mais Médicos

ABSTRACT OBJECTIVE To estimate the flow of professionals and the financial impact of the Programa Mais Médicos para o Brasil (PMMB - More Doctors for Brazil Program) within the More Doctors Program (MDP) for the Brazilian Ministry of Health and the participating municipalities of the state of São Paulo, from January 2019 to March 2022. METHODS A financial impact study was conducted in the state of São Paulo based on public secondary databases. The number of PMMB vacancies per municipality, of physicians and vulnerability profiles were described to measure the loss of replacement of professionals in the period. RESULTS In the specified period, the number of PMMB physicians in participating cities will decrease from 2,533 to 320, and the number of participating municipalities from 373 to 86. The municipalities that will need to replace the physicians will have a financial impact of R$ 929,487,904.77 (with sensitivity analysis, ranging from R$ 650,641,533.34 to R$ 1,208,334,276.20). CONCLUSION The change of vulnerability methodology adopted for the PMMB will represent serious consequences, that is, less population assistance and high financial impact for the municipalities of the state of São Paulo in a scenario of budget limitations.

RESUMO OBJETIVO Calcular o fluxo de profissionais e o impacto financeiro do Projeto Mais Médicos para o Brasil (PMMB), dentro do Programa Mais Médicos (PMM), para o Ministério da Saúde e os municípios do estado de São Paulo aderentes, no período de janeiro de 2019 a março de 2022. MÉTODOS Realizou-se estudo de impacto financeiro a partir de bases de dados secundários públicos do estado de São Paulo. O número de vagas do PMMB por município, de médicos do projeto e os perfis de vulnerabilidade foram descritos para dimensionar a perda de reposição de profissionais no período. RESULTADOS No intervalo de tempo especificado, o número de médicos do PMMB em cidades a ele aderentes passará de 2.533 para 320, e o número de municípios participantes de 373 para 86. O impacto orçamentário para os municípios que necessitarão repor médicos será de R$ 929.487.904,77 (com análise de sensibilidade variando de R$ 650.641.533,34 a R$ 1.208.334.276,20). CONCLUSÃO A mudança de metodologia da vulnerabilidade adotada para o PMMB trará sérias consequências, ou seja, desassistência da população e alto impacto financeiro para os municípios do estado de São Paulo em um cenário de limitações orçamentárias.

Microbial Food-Web Drivers in Tropical Reservoirs.

Element cycling in aquatic systems is driven chiefly by planktonic processes, and the structure of the planktonic food web determines the efficiency of carbon transfer through trophic levels. However, few studies have comprehensively evaluated all planktonic food-web components in tropical regions. The aim of this study was to unravel the top-down controls (metazooplankton community structure), bottom-up controls (resource availability), and hydrologic (water residence time) and physical (temperature) variables that affect different components of the microbial food web (MFW) carbon stock in tropical reservoirs, through structural equation models (SEM). We conducted a field study in four deep Brazilian reservoirs (Balbina, Tucuruí, Três Marias, and Funil) with different trophic states (oligo-, meso-, and eutrophic). We found evidence of a high contribution of the MFW (up to 50% of total planktonic carbon), especially in the less-eutrophic reservoirs (Balbina and Tucuruí). Bottom-up and top-down effects assessed through SEM indicated negative interactions between soluble reactive phosphorus and phototrophic picoplankton (PPP), dissolved inorganic nitrogen, and heterotrophic nanoflagellates (HNF). Copepods positively affected ciliates, and cladocerans positively affected heterotrophic bacteria (HB) and PPP. Higher copepod/cladoceran ratios and an indirect positive effect of copepods on HB might strengthen HB-HNF coupling. We also found low values for the degree of uncoupling (D) and a low HNF/HB ratio compared with literature data (mostly from temperate regions). This study demonstrates the importance of evaluating the whole size spectrum (including microbial compartments) of the different planktonic compartments, in order to capture the complex carbon dynamics of tropical aquatic ecosystems.

Coupling Between Heterotrophic Nanoflagellates and Bacteria in Fresh Waters: Does Latitude Make a Difference?

Recent studies reported comparatively lower heterotrophic bacteria (HB) abundances in tropical regions, indicating that factors involved in bacterial losses could be more relevant in the tropics. Heterotrophic nanoflagellates (HNF) are considered the main predators of HB in aquatic ecosystems, and one should expect higher abundances in the tropics because of differences in the food web configuration (absence of large daphnids). However, there are no comprehensive studies comparing HB and HNF abundances in a latitudinal gradient. We hypothesized that HB abundance would be lower in the tropics because HNF abundance would be higher, resulting in a tighter HNF-HB coupling. To test this hypothesis, we compiled a large dataset of HB and HNF abundances from tropical and temperate freshwater environments. We found that both HB and HNF abundances were lower in the tropical region, and that HNF-HB coupling does not differ between temperate and tropical regions. The lower HNF abundance and lack of coupling may be explained by a strong top-down control on HNF and/or their herbivory preference. Besides, no relationship was found between bacterial specific growth rate and either chlorophyll-a and HB abundance, indicating that bacterial losses may have an important role in tropical freshwaters. Thus, we found that HNF is likely not the main controllers of HB abundance, and that grazing by ciliates and cladocerans, together with the physiological effects of higher temperatures, may explain the high bacterial loss rates in the tropics.

Oral Outbreak of Chagas Disease in Santa Catarina, Brazil: Experimental Evaluation of a Patient's Strain.

Chagas disease is a worldwide public health problem. Although the vectorial transmission of Chagas disease has been controlled in Brazil there are other ways of transmission, such as the ingestion of T. cruzi contaminated food, which ensures the continuation of this zoonosis. Here, we demonstrate the influence of the inoculation route on the establishment and development of the SC2005 T. cruzi strain infection in mice. Groups of Swiss mice were infected intragastrically (IG) or intraperitoneally (IP) with the T. cruzi SC2005 strain derived from an outbreak of oral Chagas disease. The results revealed that 100% of IP infected mice showed parasitemia, while just 36% of IG infected showed the presence of the parasite in blood. The parasitemia peaks were later and less intense in the IG infected mice. Mortality of the IP infected animals was more intense and earlier when compared to the IG infected mice. In the IP infected mice leucopenia occurred in the early infection followed by leucocytosis, correlating positively with the increase of the parasites. However, in the IG infected mice only an increase in monocytes was observed, which was positively correlated with the increase of the parasites. Histopathological analyses revealed a myotropic pattern of the SC2005 strain with the presence of inflammatory infiltrates and parasites in different organs of the animals infected by both routes as well as fibrosis foci and collagen redistribution. The flow cytometric analysis demonstrated a fluctuation of the T lymphocyte population in the blood, spleen and mesenteric lymph nodes of the infected animals. T. cruzi DNA associated with the presence of inflammatory infiltrates was detected by PCR in the esophagus, stomach and intestine of all infected mice. These findings are important for the understanding of the pathogenesis of T. cruzi infection by both inoculation routes.

Applications of visual evoked potentials and Fourier-domain optical coherence tomography in Parkinson's disease: a controlled study.

PURPOSE: The goal of this cross-sectional observational study was to quantify the pattern-shift visual evoked potentials (VEP) and the thickness as well as the volume of retinal layers using optical coherence tomography (OCT) across a cohort of Parkinson's disease (PD) patients and age-matched controls. METHODS: Forty-three PD patients and 38 controls were enrolled. All participants underwent a detailed neurological and ophthalmologic evaluation. Idiopathic PD cases were included. Cases with glaucoma or increased intra-ocular pressure were excluded. Patients were assessed by VEP and high-resolution Fourier-domain OCT, which quantified the inner and outer thicknesses of the retinal layers. VEP latencies and the thicknesses of the retinal layers were the main outcome measures. RESULTS: The mean age, with standard deviation (SD), of the PD patients and controls were 63.1 (7.5) and 62.4 (7.2) years, respectively. The patients were predominantly in the initial Hoehn-Yahr (HY) disease stages (34.8% in stage 1 or 1.5, and 55.8 % in stage 2). The VEP latencies and the thicknesses as well as the volumes of the retinal inner and outer layers of the groups were similar. A negative correlation between the retinal thickness and the age was noted in both groups. The thickness of the retinal nerve fibre layer (RNFL) was 102.7 µm in PD patients vs. 104.2 µm in controls. CONCLUSIONS: The thicknesses of retinal layers, VEP, and RNFL of PD patients were similar to those of the controls. Despite the use of a representative cohort of PD patients and high-resolution OCT in this study, further studies are required to establish the validity of using OCT and VEP measurements as the anatomic and functional biomarkers for the evaluation of retinal and visual pathways in PD patients.

Applications of visual evoked potentials and Fourier-domain optical coherence tomography in Parkinson's disease: a controlled study / Potenciais evocados visuais e tomografia de coerência óptica com domínio de Fourier na doença de Parkinson: um estudo controlado

Purpose: The goal of this cross-sectional observational study was to quantify the pattern-shift visual evoked potentials (VEP) and the thickness as well as the volume of retinal layers using optical coherence tomography (OCT) across a cohort of Parkinson's disease (PD) patients and age-matched controls. Methods: Forty-three PD patients and 38 controls were enrolled. All participants underwent a detailed neurological and ophthalmologic evaluation. Idiopathic PD cases were included. Cases with glaucoma or increased intra-ocular pressure were excluded. Patients were assessed by VEP and high-resolution Fourier-domain OCT, which quantified the inner and outer thicknesses of the retinal layers. VEP latencies and the thicknesses of the retinal layers were the main outcome measures. Results: The mean age, with standard deviation (SD), of the PD patients and controls were 63.1 (7.5) and 62.4 (7.2) years, respectively. The patients were predominantly in the initial Hoehn-Yahr (HY) disease stages (34.8% in stage 1 or 1.5, and 55.8 % in stage 2). The VEP latencies and the thicknesses as well as the volumes of the retinal inner and outer layers of the groups were similar. A negative correlation between the retinal thickness and the age was noted in both groups. The thickness of the retinal nerve fibre layer (RNFL) was 102.7 μm in PD patients vs. 104.2 μm in controls. Conclusions: The thicknesses of retinal layers, VEP, and RNFL of PD patients were similar to those of the controls. Despite the use of a representative cohort of PD patients and high-resolution OCT in this study, further studies are required to establish the validity of using OCT and VEP measurements as the anatomic and functional biomarkers for the evaluation of retinal and visual pathways in PD patients. .

Objetivo: Este estudo observacional transversal controlado visou quantificar os potenciais evocados visuais com estímulo de padrões alternantes (PEV), a espessura e o volume das camadas retinianas com tomografia de coerência óptica (TCO) num grupo de pacientes com doença de Parkinson (DP). Métodos: Quarenta e três pacientes com DP e 38 controles. Procedimentos: pacientes e controles foram submetidos a exames neurológico e oftalmológico detalhados, sendo incluídos pacientes com DP idiopática e excluídos casos com glaucoma ou aumento da pressão intraocular. Todos os participantes foram estudados com PEV e TCO de Fourier, sendo quantificadas as latências de P100, a espessura e o volume das camadas retinianas interna e externa. Resultados: A média das idades e desvio-padrão dos pacientes com DP e controles foram respectivamente 63,1(7,5) e 62,4 (7,2) anos. Os pacientes com DP situaram-se predominantemente nos estágios iniciais de Hoehn-Yahr (34.8% no estágio 1 ou 1.5; 55.8 % no estágio 2). Não foram observadas diferenças entre os dois grupos quanto às latências dos PEV, a espessura e o volume das camadas retinianas. Observamos uma correlação negativa entre a espessura das camadas retinianas e a idade em ambos os grupos. Não se observou diferença significativa quanto à espessura da camada retiniana das fibras do nervo óptico (CRFNO), que foi de 102,7 μm nos pacientes e 104,2 μm nos controles. Conclusões: A espessura das camadas retinianas, os PEV e a espessura da CRFNO foi semelhante nos pacientes com DP e controles. Apesar desse grupo representativo de pacientes com DP e da alta resolução da TCO utilizada neste estudo, mais estudos são necessários para estabelecer o papel da TCO e dos PEV como biomarcadores anatômico e funcional na avaliação ...

Avaliação da infecção experimental de camundongos suíços infectados com um isolado de Trypanosoa cruzi proveniente de surto oral da Doença de Chagas em Santa Catarina, Brasil / Evaluation of experimental infection of Swiss mice infected with an isolate of Trypanosoa cruzi from oral outbreak of Chagas disease in Santa Catarina, Brazil

A doença de Chagas é um problema de saúde pública mundial e acomete cerca de 10 milhões de pessoas. As formas de transmissão desta doença são variadas e embora a transmissão vetorial tenha sido controlada no Brasil, outras formas de transmissão asseguram a manutenção desta zoonose, como a contaminação pela ingestão de alimentos contaminados com T. cruzi. Os recentes surtos orais da doença tem enfatizado a importância dessa via de transmissão nas infecções humanas. Evidenciando a necessidade de obtenção de dados que pudessem esclarecer os mecanismos envolvidos nesta forma de infecção pelo T. cruzi, o objetivo deste trabalho foi estudar o comportamento da cepa SC2005, isolada de um surto de transmissão oral, no modelo murino. Deste modo, camundongos suíços foram infectados por via intragástrica (IG) ou por via intraperitoneal (IP) com formas tripomastigostas de T. cruzi derivadas de cultura. Para avaliação da infecção analisou-se a parasitemia, contagem de leucócitos totais e específicos, índice tímico e esplênico, dosagem de anticorpos (IgG e IgM), análise histopatológica, PCR, citometria de fluxo e mortalidade. A parasitemia mostrou-se diferente nos dois grupos, com picos parasitêmicos mais tardios e menos intensos nos camundongos infectados via IG. A mortalidade dos animais infectados por via IP foi mais acentuada e mais precoce quando comparada com a via IG. Nos camundongos infectados por via IP ocorreu no inicio da infecção leucopenia seguida de leucocitose, correlacionada positivamente ao aumento de parasitos. Entretanto, na infecção por via IG foi observado somente aumento dos monócitos correlacionado positivamente ao aumento de parasitos. A análise histopatológica mostrou um padrão miotrópico desta cepa, com a presença de infiltrados inflamatórios e parasitos em diferentes órgãos independente da via de infecção, além de focos de fibrose e redistribuição do colágeno. Hematopoiese extramedular foi vista no fígado e no linfonodo dos camundongos infectados. Os órgãos linfoides mostraram-se bastante ativados, exceto o timo, que não apresentou alteração. Estes dados confirmam os resultados observados com o índice esplênico, que estava elevado nos camundongos infectados por ambas as vias, enquanto o índice tímico estava próximo ao normal. A análise da citometria de fluxo demonstrou uma flutuação da população de linfócitos T no sangue, linfonodo mesentérico e baço nos animais infectados. Um aumento na proporção da população de células TCD8+ foi observado no sangue e baço, enquanto uma diminuição na proporção de células TCD4+ foi observada no linfonodo mesentérico. Esta variação demonstrou uma resposta específica e coordenada de diferentes regiões contra o parasito. A produção de anticorpos IgM e IgG foi baixa no momento inicial da infecção por via IP e elevada no transcorrer da infecção independente da via de infecção. DNA de T. cruzi associados à presença de infiltrados inflamatórios foram evidenciados pela PCR no esôfago, estômago e intestino de todos os camundongos infectados. Os resultados obtidos no presente estudo demonstraram a influência da via de inoculação no estabelecimento e desenvolvimento da infecção pela cepa SC2005.

Avaliação da agregação plaquetária e dosagem do fibrinogênio em pacientes com doenças cardiovasculares e sua correlação com o uso de aspirina e fatores de risco coronariano / Evaluation of platelet aggregation and level of fibrinogen in patients with cardiovascular diseases and the correlation of taking aspirin with coronary risk factors

OBJETIVO: Avaliar a resistência à aspirina em pacientes com doenças cardiovasculares. Avaliar a dosagem do fibrinogênio sérico em pacientes usuários de aspirina, comparando-a com os que não a utilizam. Correlacionar a agregação plaquetária e o fibrinogênio sérico com parâmetros ligados ao risco cardiovascular. MÉTODO: Oitenta e dois pacientes divididos em dois grupos: grupo 1 - 41 pacientes que utilizaram aspirina na dose de 100mg/dia e grupo 2 - 41 pacientes que não utilizaram antiagregante plaquetário. Foram coletados dados epidemiológicos quanto a idade, sexo, tabagismo, etilismo, e foram realizadas dosagens de fibrinogênio sérico e agregação plaquetária. RESULTADOS: Nos grupos analisados, a idade avançada (p=0,011), o tabagismo (p=0,009) e o etilismo (p=0,007) apresentaram associação direta com o fibrinogênio sérico. Não houve correlação entre tabagismo, etilismo, fibrinogênio sérico e os valores da agregação plaquetária (p>0,05). No grupo 1, 29 por cento dos pacientes apresentaram resistência à aspirina. Destes, os tabagistas (p=0,029) e os etilistas (p=0,033) exibiram fibrinogênio sérico mais elevado. CONCLUSÃO: A resistência à aspirina esteve presente em número elevado de pacientes. Além disso, idade avançada, tabagismo e etilismo influenciaram diretamente o fibrinogênio sérico.

OBJECTIVE: To evaluate aspirin resistance in patients with cardiovascular diseases and to compare the amount of serum fibrinogen in patients taking aspirin with those who do not. To correlate the platelet aggregation and serum fibrinogen to cardiovascular risk parameters. METHODS: Eighty-two patients were divided into two groups: Group 1 - 41 patients who took 100mg aspirin daily and Group 2 - 41 patients who did not utilized platelet antiaggregates. Epidemiological data were collected including age, gender and information on smoking and alcohol intake and serum fibrinogen and platelet aggregation were mesured. RESULTS: In the groups analyzed, advanced age (p=0.011), smoking (p=0.009) and alcoholism (p=0.007) were directly associated to the serum fibrinogenen level. There were no correlations between smoking, alcoholism, serum fibrinogen and platelet aggregation values (p>0.05). In Group 1, 29 percent of the patients presented with aspirin resistance. Of these, smokers (p=0.029) and the alcoholics (p=0.033) had higher serum fibrinogen levels. CONCLUSION: Aspirin resistance was present in a high number of patients. Moreover, advanced age, smoking and alcoholism had a direct influence on the serum fibrinogen levels.