Elevated alpha-synuclein caused by SNCA gene triplication impairs neuronal differentiation and maturation in Parkinson's patient-derived induced pluripotent stem cells

We have assessed the impact of α-synuclein overexpression on the differentiation potential and phenotypic signatures of two neural-committed induced pluripotent stem cell lines derived from a Parkinson´s disease patient with a triplication of the human SNCA genomic locus. In parallel, comparative studies were performed on two control lines derived from healthy individuals and lines generated from the patient iPS-derived neuroprogenitor lines infected with a lentivirus incorporating a small hairpin RNA to knock down the SNCA mRNA. The SNCA triplication lines exhibited a reduced capacity to differentiate into dopaminergic or GABAergic neurons and decreased neurite outgrowth and lower neuronal activity compared with control cultures. This delayed maturation phenotype was confirmed by gene expression profiling, which revealed a significant reduction in mRNA for genes implicated in neuronal differentiation such as delta-like homolog 1 (DLK1), gamma-aminobutyric acid type B receptor subunit 2 (GABABR2), nuclear receptor related 1 protein (NURR1), G-protein-regulated inward-rectifier potassium channel 2 (GIRK-2) and tyrosine hydroxylase (TH). The differentiated patient cells also demonstrated increased autophagic flux when stressed with chloroquine. We conclude that a two-fold overexpression of α-synuclein caused by a triplication of the SNCA gene is sufficient to impair the differentiation of neuronal progenitor cells, a finding with implications for adult neurogenesis and Parkinson´s disease progression, particularly in the context of bioenergetic dysfunction.Fil: Oliveira, L. M. A.. Max-Planck-Institut für biophysikalische Chemie; AlemaniaFil: Falomir Lockhart, Lisandro Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina. Max-Planck-Institut für biophysikalische Chemie; AlemaniaFil: Botelho, M. G.. Max-Planck-Institut für biophysikalische Chemie; Alemania. Universidade Federal do Rio de Janeiro; BrasilFil: Lin, K. H.. Max-Planck-Institut für biophysikalische Chemie; AlemaniaFil: Wales, P.. Universität Göttingen; AlemaniaFil: Koch, J. C.. Universität Göttingen; AlemaniaFil: Gerhardt, Elizabeth. Universität Göttingen; AlemaniaFil: Taschenberger, H.. Max-Planck-Institut für biophysikalische Chemie; AlemaniaFil: Outeiro, T. F.. Universität Göttingen; AlemaniaFil: Lingor, P.. Universität Göttingen; AlemaniaFil: Schüele, B.. The Parkinson’s Institute; Estados UnidosFil: Arndt Jovin, D. J.. Max-Planck-Institut für biophysikalische Chemie; AlemaniaFil: Jovin, T. M.. Max-Planck-Institut für biophysikalische Chemie; Alemani

Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD:implication for COPD-associated neuropathogenesis

The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD

A MENINA-MOÇA QUE ESCREVIA CARTAS. O QUE A REFORMA PSIQUIÁTRICA TEM A ENFRENTAR NO CAMPO DA INFÂNCIA E ADOLESCÊNCIA?

This article analyzes the practices that the Brazilian Psychiatric Reform still has to confront in the field of child and youth mental health. The analysis is carried out through the formulation of a case: “The Young Girl who used to write letters”. In the letters written by the Young Girl she requests to go away, especially from the shelter where she was institutionalized. In this case, we see the “inevitable path” of the sheltering process, as it is described by the professionals of the public instances responsible for sending the children and teenagers to such institutions. Furthermore, we analyze the effects of nursing home practices, which include the homogenization of care, seclusion and infantilization. Alongside the story of the Young Girl there is a narrative about “Maria”, a character who shows, in her own manner, ways of dealing with the people in the shelter, especially the girls. By doing that, she forces the invention of care practices in this institution and manifests an attitude of contestation towards naturalized practices.O artigo analisa as práticas que a Reforma Psiquiátrica tem a enfrentar no campo da Saúde Mental Infantojuvenil por meio da montagem de um caso – “A Menina-moça que escrevia cartas”.  Nas correspondências feitas pela Menina-moça havia pedidos de saída, sobretudo do Abrigo onde era institucionalizada. Com este caso, vemos o “inevitável caminho” do abrigamento, tal como é considerado pelos profissionais de instâncias encaminhadoras. Debruçamo-nos sobre os efeitos das práticas asilares, entre eles o que envolve homogeneização do cuidado, reclusão e infantilização. Junto à história da Menina-moça atravessa uma narrativa de “Maria”, que mostra, com seu jeito, maneiras de lidar com as pessoas do Abrigo, em especial, com as meninas, forçando invenções das práticas de cuidado nesta instituição e formando uma postura em campo de contestar as práticas naturalizadas

Alimentação popular em São Paulo (1920 a 1950): políticas públicas, discursos técnicos e práticas profissionais

This article discusses how the concept of lower-class eating habits came about and developed in the intellectual circles of São Paulo during the first half of the 20th century. It starts by reconstructing the elements of the debate around the income and ignorance of the underprivileged as the main reasons behind their bad eating habits. Then, it looks at the focal points for interventions and public policies proposed by the government to deal with the problem thus identified, namely: training methods to produce sanitation counselors capable of offering dietary guidance as well; popular educational campaigns and new learning sites in addition to schools (e.g. healthcare centers and households); lunch and other means of offering food at schools; and diagnostic studies about food intake and eating habits among laborers. Because they were translated into technical and scientific language, the proposals and policies implemented in São Paulo left traces in a variety of supporting documents and media (photographs, primers, posters, inquiry notebooks, and academic literature).O artigo discute a construção da idéia de alimentação popular nos meios intelectuais em São Paulo, na primeira metade do século XX. Para isso, reconstitui, como motivos da má alimentação, elementos do debate em torno da renda e da ignorância dos mais pobres. Identificado o problema, as propostas de intervenção e as políticas públicas concentraram-se em alguns setores, abordados neste trabalho: métodos para a formação de educadores sanitários aptos a atuar também na educação alimentar; campanhas de instrução popular e criação de novos lugares de aprendizado (além das escolas, os centros de saúde e os lares); merenda escolar e outras alternativas de alimentação nas escolas; e diagnósticos referentes ao conteúdo e à forma da alimentação dos operários. Traduzidas em discurso técnico-científicos, as propostas e políticas implementadas na cidade deixaram indícios em documentação de suporte e tipologia variados (fotografias, cartilhas, cartazes, cadernetas de inquéritos e textos acadêmicos).Universidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

TABAGISMO: PLANEJAR OU NÃO PLANEJAR PARAR DE FUMAR

O objetivo deste trabalho foi analisar as características sóciodemográficas e status do tabagismo em ex-fumantes que pararam de fumar com e sem planejamento. E a partir deste, analisar as diferenças quanto ao sucesso na primeira tentativa e motivo intrínseco como fator facilitador à cessação nos dois grupos. Concluiu-se que os ex-fumantes do grupo sem planejamento tiveram menor carga tabágica, pararam sem motivo aparente e ficaram mais tempo sem fumar que aqueles do grupo que planejaram. Palavras-Chave: Tabagismo; Motivação; Planejamento; Ex-fumantes; Cessação

SÍNDROME DE BURNOUT EM TRABALHADORES DO CENTRO INTEGRADO DE ASSISTÊNCIA PSICOSSOCIAL - CIAPS ADAUTO BOTELHO DA CIDADE DE CUIABÁ MATO GROSSO

O objetivo deste trabalho foi avaliar a ocorrência da Síndrome de Burnout nos profissionais do CIAPS – Adauto Botelho da cidade de Cuiabá/MT, relacionar os principais sintomas da síndrome e medir a ocorrência do estresse nos profissionais pesquisados. Conclui-se que a incidência do nível de estresse nesses funcionários é de 48,6% e destes funcionários, 9,9% estariam impossibilitados de trabalhar devido ao resultado da Síndrome de Burnout. Nos sujeitos que apresentaram estresse (N=41), que corresponde a 57,7% da amostra houve um predomínio dos sintomas psicológicos.  Palavras-Chave: Burnout; Estresse; Saúde Mental; Ciaps Adauto Botelho.

Uma capitania dos novos tempos: economia, sociedade e política na São Paulo restaurada (1765-1822)

O artigo reflete sobre a trajetória da Capitania de São Paulo, a partir de 1750, apontando sua transformação, de fronteira e "boca do sertão", para território estratégico da conquista e defesa das partes meridionais e área economicamente integrada aos circuitos mercantis atlânticos.In this article, we reflect upon the history of the Captaincy of São Paulo as from 1750, drawing attention to its transformation from frontier land and "door to the backcountry" into a territory of strategic value for the purposes of conquest and defense of the southern regions, and economically integrated into the Atlantic trade routes

Determinación de la severidad de lesiones de caries interproximales en molares evaluados por diferentes métodos de detección en escolares atendidos en Clínicas Odontológicas, Universidad de Talca, año 2018.

95 p.Introducción: La caries dental es un problema de salud mundial. En Chile, la prevalencia de caries es 71% y 63% a los 6 y 12 años, respectivamente. Las lesiones de caries interproximales no cavitadas son difíciles de detectar, y conocer su prevalencia en estadios tempranos favorecería un tratamiento adecuado y permitiría su control a lo largo del tiempo. Objetivo: Determinar la severidad de las lesiones de caries interproximales en molares de niños de 6 a 12 años atendidos en las clínicas odontológicas de la Universidad de Talca utilizando diferentes métodos de diagnóstico. Metodología: Se realizó un estudio descriptivo transversal con una muestra por conveniencia de 39 pacientes. Dos examinadores calibrados evaluaron las superficies interproximales de molares de cada niño mediante el uso de criterios ICDAS, con radiografías bitewing, con la cámara SOPROlife y clínicamente después de la separación dental con el uso de gomas de ortodoncia. Los datos fueron analizados en el SPSS (vs 22.0) y considerados estadísticamente significativos en el nivel de 5%. Resultados: De los 39 niños evaluados, se observó que, para los dientes primarios, la arcada superior y el cuadrante superior izquierdo presentan la mayor prevalencia de caries. Se evidenció que un 25% de las lesiones ICDAS 4 y un 54% de las lesiones radiográficas D1 no estaban cavitadas posterior a la separación dentaria con gomas de ortodoncia (p<0,001 y p=0,38 respectivamente). Al evaluar las fotos tomadas con la cámara SOPROlife, las lesiones ICDAS 4 se ven más rojas que las ICDAS 2; una lesión D3 posee menos luminosidad y es más roja que una E1; finalmente, las lesiones cavitadas eran más oscuras y más rojas que las no cavitadas (p>0,05). Conclusión: La severidad de las lesiones de caries interproximales en molares mostró una tendencia a ser alta o muy alta, con una elevada prevalencia de lesiones cavitadas y con algún nivel de compromiso dentinario. La discordancia encontrada entre los métodos de diagnóstico fueron la separación dentaria usando las gomas de ortodoncia con los criterios ICDAS; radiografías bitewing con la separación dentaria usando las gomas de ortodoncia; y radiografías bitewing con fotografías tomadas por la cámara SOPROlife. Palabras clave: Prevalencia de caries, severidad de caries, superficie interproximal, ICDAS, radiografía bitewing, SOPROlife, gomas de ortodoncia

Moderating Perceptions of Bother Reports by Individuals Experiencing Lower Urinary Tract Symptoms

We compared reports of symptom bother for the same urinary symptoms to understand why symptom severity and bother do not correspond in a straightforward manner. We used a grounded theory approach to analyze qualitative data from 123 individual interviews and developed a conceptual framework, identifying three symptom perceptions that might “moderate” symptom bother: causal, relative, and uncertainty. Symptom bother was lower for respondents who viewed symptoms causally (symptoms seemed explainable or “normal”) or relatively (urinary symptoms were compared to other symptoms or conditions). Bother tended to be higher for respondents who viewed symptoms with uncertainty (when symptom etiology and course were unknown). A greater portion of respondents in the causal perception group had not sought health care for their symptoms. This conceptual framework is useful for understanding the relationship between reactions to and health care-seeking for other symptoms

Beyond incontinence: The stigma of other urinary symptoms

This paper is a report of a study conducted to characterize the stigma of urinary frequency and urgency and differentiate it from the stigma of incontinence and to describe race/ethnic and gender differences in the experience of stigma among a diverse sample of individuals