Intervention Models in Functional Connectivity Identification Applied to fMRI

Recent advances in neuroimaging techniques have provided precise spatial localization of brain activation applied in several neuroscience subareas. The development of functional magnetic resonance imaging (fMRI), based on the BOLD signal, is one of the most popular techniques related to the detection of neuronal activation. However, understanding the interactions between several neuronal modules is also an important task, providing a better comprehension about brain dynamics. Nevertheless, most connectivity studies in fMRI are based on a simple correlation analysis, which is only an association measure and does not provide the direction of information flow between brain areas. Other proposed methods like structural equation modeling (SEM) seem to be attractive alternatives. However, this approach assumes prior information about the causality direction and stationarity conditions, which may not be satisfied in fMRI experiments. Generally, the fMRI experiments are related to an activation task; hence, the stimulus conditions should also be included in the model. In this paper, we suggest an intervention analysis, which includes stimulus condition, allowing a nonstationary modeling. Furthermore, an illustrative application to real fMRI dataset from a simple motor task is presented

Epidemiological Analysis of 5,595 Procedures of Endovascular Correction of Isolated Descending Thoracic Aortic Disease Over 12 Years in the Public Health System in Brazil

OBJECTIVES: In Brazil, descending thoracic aorta disease, including aneurysms and dissections, is managed preferentially by endovascular treatment, owing to its feasibility and good results. In this study, we analyzed endovascular treatment of isolated descending thoracic aortic disease cases in the Brazilian public health system over a 12-year period. METHODS: Public data from procedures performed from 2008 to 2019 were extracted using web scraping techniques to assess procedure type frequency (elective or urgency), mortality, and governmental costs. RESULTS: A total of 5,595 procedures were analyzed, the vast majority of which were urgent procedures (61.82% vs. 38.18%). In-hospital mortality was lower for elective than for urgent surgeries (4.96 vs.10.32% p=0.008). An average of R$16,845.86 and R$20,012.04 was paid per elective and emergency procedure, respectively, with no statistical difference (p=0.095). CONCLUSION: Elective procedures were associated with lower mortality than urgent procedures. There was no statistically significant difference between elective and urgent procedures regarding costs

What else in times of COVID-19? The role of minimally invasive autopsy for the differential diagnosis of acute respiratory failure in a case of kala-azar

Visceral leishmaniasis (VL) is a chronic vector-borne zoonotic disease caused by trypanosomatids, considered endemic in 98 countries, mainly associated with poverty. About 50,000–90,000 cases of VL occur annually worldwide, and Brazil has the second largest number of cases in the world. The clinical picture of VL is fever, hepatosplenomegaly, and pancytopenia, progressing to death in 90% of cases due to secondary infections and multi-organ failure, if left untreated. We describe the case of a 25-year-old female who lived in the metropolitan area of Sao Paulo, who had recently taken touristic trips to several rural areas in Southeastern Brazil and was diagnosed post-mortem. During the hospitalization in a hospital reference for the treatment of COVID-19, the patient developed acute respiratory failure, with chest radiographic changes, and died due to refractory shock. The ultrasound-guided minimally invasive autopsy diagnosed VL (macrophages containing amastigote forms of Leishmania in the spleen, liver and bone marrow), as well as pneumonia and bloodstream infection by gram-negative bacilli

Complex network analysis of CA3 transcriptome reveals pathogenic and compensatory pathways in refractory temporal lobe epilepsy

We previously described - studying transcriptional signatures of hippocampal CA3 explants - that febrile (FS) and afebrile (NFS) forms of refractory mesial temporal lobe epilepsy constitute two distinct genomic phenotypes. That network analysis was based on a limited number (hundreds) of differentially expressed genes (DE networks) among a large set of valid transcripts (close to two tens of thousands). Here we developed a methodology for complex network visualization (3D) and analysis that allows the categorization of network nodes according to distinct hierarchical levels of gene-gene connections (node degree) and of interconnection between node neighbors (concentric node degree). Hubs are highly connected nodes, VIPs have low node degree but connect only with hubs, and high-hubs have VIP status and high overall number of connections. Studying the whole set of CA3 valid transcripts we: i) obtained complete transcriptional networks (CO) for FS and NFS phenotypic groups; ii) examined how CO and DE networks are related; iii) characterized genomic and molecular mechanisms underlying FS and NFS phenotypes, identifying potential novel targets for therapeutic interventions. We found that: i) DE hubs and VIPs are evenly distributed inside the CO networks; ii) most DE hubs and VIPs are related to synaptic transmission and neuronal excitability whereas most CO hubs, VIPs and high hubs are related to neuronal differentiation, homeostasis and neuroprotection, indicating compensatory mechanisms. Complex network visualization and analysis is a useful tool for systems biology approaches to multifactorial diseases. Network centrality observed for hubs, VIPs and high hubs of CO networks, is consistent with the network disease model, where a group of nodes whose perturbation leads to a disease phenotype occupies a central position in the network.Conceivably, the chance for exerting therapeutic effects through the modulation of particular genes will be higher if these genes are highly interconnected in transcriptional networks.FAPESP (09/53443-1, 05/56446-0, 05/00587-5, 11/50761-2)CNPq (305635/2009-3, 301303/06-1, 573583/2008-0

Saúde cardiovascular e habitação: um diálogo importante travado nos assentamentos precários de São Paulo

A redução das doenças infecciosas e vida mais longa favoreceram a maior prevalência das doenças crônicas como câncer, diabetes, doenças cardiovasculares e doenças respiratórias. Em geral, a escala geográfica dos estudos sobre condições socioeconômicas e problemas de saúde é o município. Nesta escala geográfica não há separação nítida entre os tipos de assentamento. Estudos intraurbanos por tipo de assentamento podem contribuir para um retrato mais fiel sobre as desigualdades nas condições de vida. Neste estudo, foram analisados dados de residentes do município de São Paulo que foram internados e os que foram a óbito, por doenças do aparelho circulatório de 2010 a 2016, para óbitos, e de 2011 a 2016, para internações. Cada internação e óbito foi atribuída ao assentamento de moradia segundo tipo: aglomerado subnormal (AGSN), precário ou regular. Foram feitos os seguintes cálculos: proporção de internações hospitalares pelo Sistema Único de Saúde (SUS) por grupos de causas, taxas padronizadas por sexo e faixa etária, Razão internação/habitante segundo sexo, faixa etária e tipo de assentamento e Taxas padronizadas por sexo e faixa etária de mortalidade por doenças do aparelho circulatório. Os resultados encontrados mostram uma situação ainda mais iníqua nos assentamentos precários para todas as faixas etárias, nos dois sexos. A diferença da saúde cardiovascular entre os três tipos de assentamentos, avaliada por meio das proporções de internações hospitalares e pelas taxas de mortalidade, evidenciam que quase 1.700 mil pessoas em São Paulo estão em grande desvantagem em relação ao grupo formado por 85% da população. Em termos de internações, as taxas são mais altas nos AGSN. Neste sentido, pode-se especular que há maior acesso ao serviço de saúde para os moradores de AGSN em relação aos de assentamentos precários. Este acesso é revertido em menor mortalidade quando as taxas dos dois grupos são comparadas. Se considerarmos apenas dois grupos (assentamentos regulares e AGSN), a situação de maior desvantagem nos assentamentos precários se dilui, tornando-se invisível. Tais resultados podem munir a vigilância em saúde para a definição de programas específicos para estes assentamentos, assim como a gestão do território, em geral, para propiciar melhores condições de moradia.The reduction of infectious diseases and longer life favored the greater prevalence of chronic diseases such as cancer, diabetes, cardiovascular and respiratory diseases. In general, the geographical scale of studies on socioeconomic conditions and health problems is the municipality. In this geographical scale there is no clear separation between the types of settlement. Intraurban studies by type of settlement can contribute to a more faithful portrait on inequalities in living conditions. In this study, data from residents of the municipality of São Paulo were analyzed who were admitted and those who died, by diseases of the circulatory system from 2010 to 2016 for deaths and from 2011 to 2016, for hospitalizations. Each hospitalization and death was attributed to the settlement of housing according to type: non-regular settlement, precarious or regular. The following calculations were made: proportion of hospital admissions by the Unified Health System (SUS) by groups of causes, standardized rates by gender and age group, hospitalization/inhabitant according to sex, age group and type of settlement and standardized rates by gender and age standardized mortality rates due to circulatory diseases. The results found an even more wicked situation in precarious settlements for all age groups, both sexes. The difference in cardiovascular health between the three types of settlements, evaluated through the proportions of hospital hospitalizations and mortality rates, show that almost 1,700,000 people in São Paulo are in a major disadvantage compared to the group formed by 85% of the population. In terms of hospitalizations, rates are higher in non-regular settlement. In this sense, it can be speculated that there is greater access to health service for residents of non-regular settlement in relation to those of precarious settlements. This access is reverted to lower mortality when the rates of both groups are compared. If we consider only two groups (regular and non-regular settlements), the situation of greater disadvantage in precarious settlements is diluted, becoming invisible. Such results can provide health surveillance to define specific programs for these settlements, as well as territory management, in general, to provide better housing conditions

Cerebral Responses to Stationary Emotional Stimuli Measured by fMRI in Women with Persistent Postural-Perceptual Dizziness

Introduction Persistent postural-perceptual dizziness (PPPD) is a functional vestibular disorder characterized by chronic dizziness, unsteadiness, and hypersensitivity to motion. Preexisting anxiety disorders and neurotic personality traits confer vulnerability to PPPD. High anxiety during acute vertigo or dizziness incites it. A functional magnetic resonance imaging (fMRI) study of chronic subjective dizziness found unexpectedly hypoactive responses to vestibular stimulation in cortical regions that integrate threat assessment and spatial perception. Objective This fMRI study used non-moving, but emotionally charged visual stimuli to investigate the brain's activity of PPPD patients and control subjects. Methods The participants included 16 women with PPPD and 16 age-matched women who recovered completely from acute episodes of vertigo or dizziness capable of triggering PPPD. Brain responses to positive, neutral, and negative figures from the International Affective Picture System were measured with fMRI and compared between the groups. Dizziness handicap, anxiety, and depression were assessed with validated questionnaires. Results Between group analyses: Participants with PPPD showed reduced activity in anterior cingulate cortex and increased activity in left angular gyrus in response to negative versus positive stimuli, which was not observed in recovered individuals. Within group analyses: Participants with PPPD had increased activity in visuospatial areas (parahippocampal gyrus, intraparietal sulcus) in negative versus positive and negative versus neutral contrasts, whereas recovered individuals had increased activity in anxiety regions (amygdala, orbitofrontal cortex). Conclusion Patients with PPPD may be more attuned to spatial elements than to the content of emotionally charged visual stimuli