Schizophrenia, brain disease and meta-analyses: Integrating the pieces and testing Fusar-Poli`s hypothesis

This paper aims to discuss and test the hypothesis raised by Fusar-Poli [Fusar-Poli P. Can neuroimaging prove that schizophrenia is a brain disease? A radical hypothesis. Medical Hypotheses in press, corrected proof] that ""on the basis of the available imaging literature there is no consistent evidence to reject the radical and provocative hypothesis that schizophrenia is not a brain disease"". To achieve this goal, all meta-analyses on `fMRI and schizophrenia` published during the current decade and indexed in Pubmed were summarized, as much as some other useful information, e.g., meta-analyses on genetic risk factors. Our main conclusion is that the literature fully supports the hypothesis that schizophrenia is a syndrome (not a disease) associated with brain abnormalities, despite the fact that there is no singular and reductionist pathway from the nosographic entity (schizophrenia) to its causes. This irreducibility is due to the fact that the syndrome has more than one dimension (e.g., cognitive, psychotic and negative) and each of them is related to abnormalities in specific neuronal networks. A psychiatric diagnosis is a statistical procedure; these dimensions are not identically represented in each diagnosticated case and this explains the existence of more than one pattern of brain abnormalities related to schizophrenia. For example, chronification is associated with negativism while the first psychotic episode is not; in that sense, the same person living with schizophrenia may reveal different symptoms and fMRI patterns along the course of his life, and this is precisely what defines schizophrenia since the time when it was called Dementia Praecox (first by pick then by Kraepelin). It is notable that 100% of the collected meta-analyses on `fMRI and schizophrenia` reveal positive findings. Moreover, all meta-analyses that found positive associations between schizophrenia and genetic risk factors have to do with genes (SNPs) especially activated in neuronal tissue of the central nervous system (CNS), suggesting that, to the extent these polymorphisms are related to schizophrenia`s etiology, they are also related to abnormal brain activity. (C) 2009 Elsevier Ltd. All rights reserved.

Down-regulation of ANAPC13 and CLTCL1: Early Events in the Progression of Preinvasive Ductal Carcinoma of the Breast

Alterations in the gene expression profile in epithelial cells during breast ductal carcinoma (DC) progression have been shown to occur mainly between pure ductal carcinoma in situ (DCIS) to the in situ component of a lesion with coexisting invasive ductal carcinoma (DCIS-IDC) implying that the molecular program for invasion is already established in the preinvasive lesion. For assessing early molecular alterations in epithelial cells that trigger tumorigenesis and testing them as prognostic markers for breast ductal carcinoma progression, we analyzed, by reverse transcription-quantitative polymerase chain reaction, eight genes previously identified as differentially expressed between epithelial tumor cells populations captured from preinvasive lesions with distinct malignant potential, pure DCIS and the in situ component of DCIS-IDC. ANAPC13 and CLTCL1 down-regulation revealed to be early events of DC progression that anticipated the invasiveness manifestation. Further down-regulation of ANAPC13 also occurred after invasion appearance and the presence of the protein in invasive tumor samples was associated with higher rates of overall and disease-free survival in breast cancer patients. Furthermore, tumors with low levels of ANAPC13 displayed increased copy number alterations, with significant gains at 1q (1q23.1-1q32.1), 8q, and 17q (17q24.2), regions that display common imbalances in breast tumors, suggesting that down-regulation of ANAPC13 contributes to genomic instability in this disease.

Discussions about Health and Illness: revisiting Monteiro Lobato's adult work

Monteiro Lobato's opinions with regard to the health and disease themes were not restricted to Jeca Tatu's condition; he went beyond, and his opinions and reports about the illness experience can be observed in several excerpts of his adult work. This paper highlights the health and illness conceptions observed in Monteiro Lobato's writings. Through the analysis of his adult work, we could learn about his opinions and reports on his beloved ones' experience of being sick, the possibility that the disease offers of socializing individuals, medical corporativism, his participation in the Pro-Sanitation League, some paternalistic health practices and the vulnerability of those with unfavorable social conditions, among other topics, in some occasions with comical characteristics, in others with resignation and even anger. Therefore, this study analyzed his adult work, discussing the excerpts that deal with health and illness experienced in the first decades of the 20th century.