Structural and functional analyzes in Parkinson's disease

Orientadores: Fernando Cendes, Anelyssa Cysne Frota D'AbreuTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Introdução: A doença de Parkinson (DP) é a segunda doença neurodegenerativa mais comum no mundo. Ela é uma doença multi-sistêmica, caracterizada por sintomas motores e não-motores. A fisiopatologia da DP ainda não foi totalmente elucidada e a maioria dos estudos de imagem já realizados, utilizaram a técnica de morfometria baseada em voxels, comparando subgrupos de pacientes, com ou sem determinados sintomas. Objetivos: Avaliar indivíduos com DP através de diferentes técnicas de análise de imagem. Métodos: Avaliamos 101 pacientes (71 homens) e 69 controles. Oitenta e cinco pacientes passaram por avaliação clínica e destes, 36 apresentaram o primeiro sintoma em hemicorpo direito, e em 56 o principal sintoma foi o tremor. Os pacientes foram avaliados através das escalas Unified Parkinson¿s Disease Rating Scale (UPDRS) (59,33±9.8), Hoehn &Yahr (H&Y) (2.84±1.2), Scales for Outcomes in Parkinson¿s Disease-Cognition (SCOPA-COG) (19.24±6.8), Scales for Outcomes in Parkinson¿s Disease - Psychiatric Complications (SCOPA-PC) (3.6±7.8), Non-Motor Symptoms Scale (NMSS) (69.57±48.19) e Escala de Schwab & England para atividades de vida diária (73%±22%).Utilizamos as seguintes técnicas de análise de imagem: imagem por tensor de difusão (DTI), análise de espessura cortical (EC) e ressonância magnética funcional em estado de repouso (rs-fMRI). Resultados: Na análise de DTI nós avaliamos três tratos: corticoespinhal, cíngulo e corpo caloso. No trato corticoespinhal encontramos aumento de anisotropia fracional (FA) e diminuição nos valores de difusividade média (MD), difusividade axial (AD) e radial (RD). No cíngulo não encontramos diferenças significativas, e no corpo caloso encontramos diminuição de FA nos pacientes. Evidenciamos também associação entre MD e RD em trato corticoespinhal e cíngulo com a SCOPA-COG; FA e RD em corpo caloso com a UPDRS-III. Valores de FA menores que 0.559467 no trato corticoespinhal, diferenciaram corretamente pacientes de controles em 85.04% dos casos, com sensibilidade de 89.04% e especificidade de 79.63%. Na análise de EC não encontramos diferenças significativas entre pacientes e controles, porém, quando dividimos os pacientes em subgrupos leve, moderado e grave encontramos diferenças nos 3 grupos. O grupo leve apresentou diminuição da EC em giro temporal superior, giro reto e córtex olfatório, já o grupo moderado apresentou diminuição da EC em giro pós-central, área motora suplementar e giro frontal inferior, e o grupo grave em giro frontal inferior, giros pré- e pós-central, área motora suplementar, giro frontal inferior, giro reto, polo temporal, giro fusiforme, giro temporal médio e giro occipital. Encontramos correlação entre os escores da UPDRS-III e EC. Considerando a análise funcional encontramos alteração de conectividade em diversas regiões como lobos frontal, temporal e occipital, tálamo e tronco cerebral. Em relação às redes funcionais encontramos alteração de conectividade na default mode network e rede visual. Conclusão: Utilizamos técnicas complementares para avaliar alterações cerebrais na DP. Demonstramos alterações estruturais e funcionais em regiões análogas, entretanto, ainda não é possível determinar se as alterações funcionais são consequência ou causa direta das alterações estruturais, ou ocorrem em paralelo como resultado da fisiopatologia da doença. Valores de FA no trato corticoespinhal podem ser utilizadas como biomarcador, porém estudos longitudinais são necessários para confirmar estes achadosAbstract: Introduction: Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. It is a multisystemic disorder characterized by motor and non-motor symptoms. The pathophysiology of PD has not been fully elucidated and previous imaging studies mostly used voxel-based morphometry, comparing subgroups of patients, with or without certain symptoms. Objectives: The aim of this study was to evaluate individuals with PD through different imaging techniques. Methods: We evaluated 101 patients (71 men) and 69 controls. Eighty-five patients underwent clinical evaluation and of those, 36 had the first symptom at right, and in 56 the main symptom was tremor. Patients were assessed through scales: Unified Parkinson's Disease Rating Scale (UPDRS) (59.33 ± 9.8), Hoehn & Yahr (H & Y) (2.84 ± 1.2), Scales for Outcomes in Parkinson's Disease-Cognition (SCOPA-COG) (19:24 ± 6.8), Scales for Outcomes in Parkinson's Disease - Psychiatric Complications (SCOPA-PC) (3.6 ± 7.8), Non-Motor Symptoms Scale (NMSS) (69.57 ± 48.19) and Schwab & England scale for activities of daily living (73% ± 22%). We use the following image analysis techniques: diffusion tensor imaging (DTI), cortical thickness analysis (CTA) and resting state functional magnetic resonance imaging (rs-fMRI). Results: In the DTI, we evaluated three tracts: corticospinal, cingulum and corpus callosum. In the corticospinal tract, we found increased fractional anisotropy (FA) and decreased mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). There were no significant differences in the cingulum, and we observed decreased FA in the corpus callosum. There was an association between MD and RD in the corticospinal tract and cingulum with the SCOPA-COG scores, and between the FA and RD in the corpus callosum and the UPDRS-III. FA values ??lower than 0.559467 in the corticospinal tract, properly differentiated patients from controls in 85.04 % of cases, with a sensitivity of 89.04% and sensitivity of 79.63%. There were no significant differences between patients and controls in CTA, however, when the patients were divided into mild, moderate and severe subgroups, we found differences in the three groups. The mild group had decreased CT in the superior temporal gyrus, gyrus rectus and the olfactory cortex, the moderate group exhibited reduced CT in the postcentral gyrus, the supplementary motor area and the inferior frontal gyrus, while the severe group presented decreased CT in the inferior frontal gyrus, precentral and postcentral gyrus, supplementary motor area, inferior frontal gyrus, gyrus rectus, temporal pole, fusiform gyrus, middle temporal gyrus and occipital gyrus. We found an association between the UPDRS-III scores and CT. We found decreased connectivity between various areas in the frontal, temporal and occipital lobes, thalamus and brainstem. We found reduced connectivity in the default mode network and the visual network. Conclusion: We used three complementary techniques to assess brain changes in PD. We demonstrated structural and functional changes in similar regions; however, it is still not possible to determine whether the functional deficits occur due to structural changes or vice versa. FA values ??in the corticospinal tract may be used as a biomarker; however, longitudinal studies are necessary to confirm these findingsDoutoradoFisiopatologia MédicaDoutora em Ciências2011/19958-4FAPES

Pattern Of Reduced Functional Connectivity And Structural Abnormalities In Parkinson's Disease: An Exploratory Study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)MRI brain changes in Parkinson's disease (PD) are controversial. Objectives: We aimed to describe structural and functional changes in PD. Methods: Sixty-six patients with PD (57.94 +/- 10.25 years) diagnosed according to the UK Brain Bank criteria were included. We performed a whole brain analysis using voxel-based morphometry (VBM-SPM 8 software), cortical thickness (CT) using CIVET, and resting-state fMRI using the Neuroimaging Analysis Kit software to compare patients and controls. For VBM and CT we classified subjects into three groups according to disease severity: mild PD [Hoehn and Yahr scale (HY) 1-1.5], moderate PD (HY 2-2.5), and severe PD (HY 3-5). Results: We observed gray matter atrophy in the insula and inferior frontal gyrus in the moderate PD and in the insula, frontal gyrus, putamen, cingulated, and paracingulate gyri in the severe groups. In the CT analysis, in mild PD, cortical thinning was restricted to the superior temporal gyrus, gyrus rectus, and olfactory cortex; in the moderate group, the postcentral gyrus, supplementary motor area, and inferior frontal gyrus were also affected; in the severe PD, areas such as the precentral and postentral gyrus, temporal pole, fusiform, and occipital gyrus had reduced cortical thinning. We observed altered connectivity at the default mode, visual, sensorimotor, and cerebellar networks. Conclusion: Subjects with mild symptoms already have cortical involvement; however, further cerebral involvement seems to follow Braak's proposed mechanism. Similar regions are affected both structurally and functionally. We believe the combination of different MRI techniques may be useful in evaluating progressive brain involvement and they may eventually be used as surrogate markers of disease progression.7FAPESP (Sao Paulo Research Foundation) [2012/05286-7, 2011/19958-4, 2013/03358-3]CNPq [74873/2010-2]FAPESPIpsenCNPq, BRAZILFAPESP, BRAZILFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Defining Metabolic Rewiring in Lung Squamous Cell Carcinoma

Metabolomics based on untargeted flow infusion electrospray ionization high-resolution mass spectrometry (FIE-HRMS) can provide a snap-shot of metabolism in living cells. Lung Squamous Cell Carcinoma (SCC) is one of the predominant subtypes of Non-Small Cell Lung Cancers (NSCLCs), which usually shows a poor prognosis. We analysed lung SCC samples and matched histologically normal lung tissues from eight patients. Metabolites were profiled by FIE-HRMS and assessed using t-test and principal component analysis (PCA). Differentially accumulating metabolites were mapped to pathways using the mummichog algorithm in R, and biologically meaningful patterns were indicated by Metabolite Set Enrichment Analysis (MSEA). We identified metabolic rewiring networks, including the suppression of the oxidative pentose pathway and found that the normal tricarboxylic acid (TCA) cycle were decoupled from increases in glycolysis and glutamine reductive carboxylation. Well-established associated effects on nucleotide, amino acid and thiol metabolism were also seen. Novel aspects in SCC tissue were increased in Vitamin B complex cofactors, serotonin and a reduction of γ-aminobutyric acid (GABA). Our results show the value of FIE-HRMS as a high throughput screening method that could be exploited in clinical contexts

ENFERMEDADES RELACIONADAS AL ESTILO DE VIDA EN LIMA, PERÚ

Introducción: Las enfermedades relacionadas al estilo de vida son uno de los mayores retos de salud del siglo 21. Objetivos: El propósito de esta investigación fue obtener una base de datos para estudiar la prevalencia de enfermedades de las personas que viven en pobreza en Lima, Perú. Metodología: La investigación estuvo localizada en los distritos de Comas y Carabayllo en Lima, Perú. Contamos con un total de 829 adultos y 770 niños (0-17 años de edad) participantes. La data fue recolectada a través de clínicas comunitarias gratuitas, estas incluyeron muestras de sangre para evaluar la hemoglobina, glucosa, hemoglobina glicosilada, lípidos, vitamina D, y anticuerpos en contra de Chagas y Helicobacter pylori. Para la población pediátrica sólo se utilizó los records médicos; no se utilizaron muestras de sangre con propósitos de investigación. Resultados: Los resultados más significativos fueron: 50,9% con presión arterial sanguínea elevada siendo sistólica o diastólica, 47% Con hemoglobina glicosilada elevada, 24% glucosa en ayuno elevada, 57,2% con un al menos un parámetro elevado del panel lípido, 32,6% hemoglobina baja, 97,2% Vitamina D baja, 59% positivo para anticuerpos de Helicobacter, y 5,6% positivo con anticuerpos de Chagas. La prevalencia de sobrepeso y obesidad fue 65,1% para adultos y 42,3% para la población pediátrica. Conclusión: Los resultados demuestran anomalías relacionadas al estilo de vida. Esta información puede utilizarse para desarrollar estrategias de prevención y tratamiento de las enfermedades relacionadas al estilo de vida, con enfoque en la educación y cambios en el estilo de vida.   DOI: https://doi.org/10.25176/RFMH.v17.n2.83

Os conceitos e as práticas de espiritualidade de pessoas que vivem com o HIV/Aids: Reflexões a partir da teoria das representações sociais / Concepts and practices of spirituality of people living with HIV/AIDS: Reflections from the theory of social representations

Objetivo: Refletir a espiritualidade a luz das representações sociais, como proposição ao cuidado em saúde para pessoas vivendo com HIV/Aids. Métodos: Estudo teórico-reflexivo orientado entre a inter-relação da Teoria das Representações Sociais com evidencias científicas entre a espiritualidade e a HIV/Aids, considerando a singularidade da síndrome e a forma como as pessoas expressam a espiritualidade e o seu significado para o cuidado em saúde. Resultados: O contexto apresentado oferece elementos para incentivar e desenvolver a espiritualidade nas ações de cuidado às pessoas vivendo com HIV/Aids, de modo a auxiliá-las no enfrentamento de sua  condição  clínica. Considerações finais: A teoria utilizada nesta reflexão atribui significados para o desenvolvimento da dimensão espiritual no cuidado humano às pessoas vivendo com HIV/aids

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly