The plague: a case of delusional infestation with folie à deux / A praga: um caso de delírio de infestação com folie à deux

Folie à deux or Shared psychotic disorder (SPD) is a rare condition characterized by shared psychotic symptoms between two or more individuals. Delusional parasitosis (DP) is an uncommon psychiatric illness in that patients believe they are infested by insects, without evidence to support this belief. DP occurs in 5­15% of SPD. We report a case of cutaneous DP with SPD between an elderly mother and a daughter that lived together and withdrew from other social contacts for the last three years. We aim to highlight the relationship between SPD and DP, its prognosis, and clinical implications.

Folie à deux ou Perturbação Psicótica Compartilhada (PPC) é uma condição rara caracterizada por sintomas psicóticos compartilhados entre dois ou mais indivíduos. O delírio parasitário (DP) é uma doença psiquiátrica incomum em que os pacientes acreditam estar infestados por insetos, sem evidências que sustentem essa crença. O DP ocorre em 5 a 15% das PPC. Relatamos um caso de um DP cutâneo com PPC entre uma mãe idosa e uma filha que viviam juntas e afastadas de outros contatos sociais nos últimos três anos. O nosso objetivo é destacar a relação entre PPC e o DP, o seu prognóstico e implicações clínicas

Identification of new human mesenchymal stem cell biomarker by aptamers / Identificação de novos biomarcadores de células tronco mesenquimais de origem humana por meio de aptâmeros

Stem cells are undifferentiated cells that can be distinguished from others by their ability to self-renew and to differentiate into new specific cell types. Mesenchymal stem cells (MSC) are adult stem cells that can be obtained from different sources, such as adipose tissue, bone marrow, dental pulp, and umbilical cord. They can either replicate, originating new identical cells, or differentiate into cells of mesodermal origin and from other germ layers. MSC have been studied as new tools for regenerative therapy. Although encouraging results have been demonstrated, MSC-based therapies still face a great barrier: the difficulty of isolating these cells from heterogeneous environments. MSC are currently characterized by immunolabelling through a set of multiple surface membrane markers, including CD29, CD73, CD90 and CD105, which are also expressed by other cell types. Hence, the present work aimed to identify new specific biomarkers for the characterization of human MSC using DNA aptamers produced by the SELEX (Systematic Evolution of Ligands by EXponential Enrichment) technique. Our results showed that MSC from different origins bound to DNA candidate aptamers, that is, DNA or RNA oligonucleotides selected from random libraries that bind specifically to biological targets. Aptamer-bound MSC could be isolated by fluorescenceactivated cell sorting (FACS) procedures, enhancing the induction of differentiation into specific phenotypes (chondrocytes, osteocytes and adipocytes) when compared to the whole MSC population. Flow cytometry analyses revealed that candidate aptamers bound to 50% of the MSC population from dental pulp and did not present significant binding rates to human fibroblasts or lymphocytes, both used as negative control. Moreover, immunofluorescence images and confocal analyses revealed staining of MSC by aptamers localized in the surfacemembrane of these cells. The results also showed internal staining of human monocytes by our investigated aptamers. A non-specific control aptamer (CNTR APT) obtained from the random pool was then utilized to compare the specificity of the aptamers bound to the analyzed non-apoptotic cells, showing no staining for MSC. However, 40% of the monocytes bound to the CNTR APT. Normalized data based on the cells bound to candidate aptamers compared to those bound to the CNTR APT, revealed a 10 to 16-fold higher binding rate for MSC against 2-fold for monocytes. Despite its low specificity, monocyte-aptamer binding occurs probably due to the expression of shared markers with MSC, since monocytes are derived from hematopoietic stem cells and are important for the immune system ability to internalize/phagocyte external molecules. Given that, we performed a pull-down assay followed by mass spectrometry analysis to detect which MSC-specific protein or other target epitope not coexpressed by monocytes or the CNTR APT would bind to the candidate aptamer. Distinguishing between MSC and monocyte epitopes is important, as both cells are involved in immunomodulatory effects after MSC transplantations. ADAM17 was found to be a target of the APT10, emerging as a possible biomarker of MSC, since its involvement in the inhibition of the TGF signaling cascade, which is responsible for the differentiation of MSC. Thus, MSC with a higher stemness profile should overexpress the protein ADAM17, which presents a catalytic site with affinity to APT10. Another target of Apt 10 is VAMP3, belonging to a transmembrane protein complex that is involved in endocytosis and exocytosis processes during immune and inflammatory responses. Overall, proteins identified as targets of APT10 may be cell surface MSC biomarkers, with importance for MSC-based cell and immune therapies

Células tronco são células indiferenciadas que podem ser distinguidas de outros tipos celulares por meio da habilidade de se auto renovarem e de se diferenciarem em novos tipos celulares. Células tronco mesenquimais (MSC) são células tronco adultas encontradas em diferentes tecidos como tecido adiposo, polpa de dente e cordão umbilical. Estas células podem se autodividir em células idênticas ou se diferenciarem em células de origem mesodermal. Estas células têm sido estudadas em novas aplicações que envolvem terapia regenerativas. Embora resultados encorajadores tenham sido demonstrados, terapias que utilizam MSC ainda encontram uma grande barreira: a dificuldade no isolamento destas células a partir de um ambiente heterogêneo. MSC são caracterizadas por populações positivas em ensaios de imunomarcação para os epítopos membranares CD29, CD73, CD90 e CD105, presentes também em outros tipos celulares. Assim, o presente trabalho tem o objetivo de identificar novos biomarcadores de MSC de origem humana, utilizando aptâmeros de DNA produzidos pela técnica SELEX (Systematic Evolution of Ligands by EXponential Enrichment) como ferramenta. Nossos resultados mostraram que MSC de diferentes origens ligam-se a aptâmeros (oligonucleotídeos de DNA ou RNA que atuam como ligantes específicos de alvos moleculares) de DNA candidatos que atuam no isolamento de MSC por meio da técnica FACS de separação celular, promovendo uma maior indução de diferenciação em células específicas (condrócitos, osteócitos e adipócitos) comparada com a população total de MSC. Análises de citometria de fluxo mostraram que os aptâmeros candidatos se ligam a 50% das MSC de polpa de dente e não apresentam taxa de ligação significante para fibroblastos e linfócitos de origem humana - utilizados como controles negativo. Além domais, imagens de imunofluorescência e confocal mostraram ligação na superfície da membrana de MSC e a marcação interna de monócitos a estes aptâmeros. Portanto, um aptâmero controle (CNTR APT) foi utilizado para comparar a especificidade dos aptâmeros ligados a células viáveis, mostrando a não ligação deste aptâmero a MSC. Porém, 40% da população de monócitos ligou-se ao CNTR APT. Uma normalização baseada na comparação entre as taxas de ligação entre células ligadas com aptâmeros candidatos e o aptâmero controle gerou uma taxa de especificidade entre 10-16 vezes maior para MSC contra 2,5 vezes para os monócitos. Deste modo, embora os resultados tenham mostrado uma taxa de ligação entre monócitos e aptâmeros, as MSC ligadas aos aptâmeros candidatos possuem uma maior taxa de especificidade devido a uma maior presença de antígenos que são expressos em ambas as células. Um ensaio de Pull Down seguido de espectrometria de massas foi utilizado para a identificação de biomarcadores que se ligariam aos aptâmeros candidatos, e que não seriam co-expressos por monócitos e por antígenos ligados ao aptâmero controle. Deste modo, a proteína ADAM17 foi identificada nas amostras de APT10 ligadas às MSC. Tal proteína está relacionada à inibição de uma cascata de sinalização da família de proteínas TGF, responsável pela diferenciação de MSC. Assim, MSC com maior potencial tronco deveriam expressar ADAM17 em maior quantidade. Tal proteína apresenta um sítio catalítico que demonstra interagir com o APT10, de acordo com predição Docking entre proteína e DNA. Foi identificada também, a proteína VAMP3, que pertence a um complexo proteico transmembranar responsável pelos processos de endocitose e exocitose, e que podem ter um papel importante na liberação de citocinas e outras moléculas relacionadas às respostas imune e inflamatórias. Deste modo, o APT10 identificou proteínas importantes que devem estar relacionas com a melhora de imunoterapias que utilizam MSC

Exploring the shared genes of hypertension, diabetes and hyperlipidemia based on microarray

Given their relationship with metabolic syndrome and systematic inflammatory diseases, the pathogenesis of hypertension, hyperglycemia, and hyperlipidemia is closely related. To explore the common genes among these three conditions, spontaneous hypertensive rats (SHR), spontaneous diabetic Goto-Kakizaki rats (GK) and hyperlipidemia rats (HMR) were reared for experiments. Gene array was used to identify the genes of SHR, GK and HMR compared with normal Wistar rats using TBtools software. First, real-time PCR was applied to verify these genes, and Cytoscape software was used to construct networks based on the National Center for Biotechnology Information (NCBI) database. Second, Kyoto Encyclopedia of Genes and Genomes (KEGG) database analysis was performed to classify the genes. Visualization and Integrated Discovery (DAVID) database and Gene Ontology database were used to explore the biological function. Finally, Onto-tools Pathway Express was used to analyze the pathways of shared genes. Importantly, upregulated common genes, such as Bad, Orm1, Arntl and Zbtb7a, were used to construct a network of 150 genes, while downregulated genes, such as Mif and Gpx1, formed a network of 29 genes. Interestingly, the networks were involved in various pathways, such as insulin signal pathway, endometrial cancer pathway, circadian rhythm pathway, and pancreatic cancer pathway. We discovered common genes of SHR, GK and HMR compared with normal Wistar rats, and the association of these genes together with biological function were preliminarily revealed.

Tamización poblacional para la detección temprana del cáncer de próstata: ¿Qué hemos aprendido en los últimos 10 años? / Population Screening for Early Detection of Prostate Cancer: ¿What have we Learned in the Last Decade?

Introducción Desde el inicio de la aplicación del cribado para cáncer de próstata basado en el antígeno prostático específico (PSA) hace aproximadamente dos décadas, la controversia sobre los beneficios y desventajas de su uso rutinario ha sido constante. La literatura médica cuenta con múltiples estudios que en ocasiones han revelado resultados contradictorios sobre los posibles beneficios de la tamización con PSA; la tasa de detección de cáncer de próstata indolente detectado parece ser alta y los estudios no demuestran de forma constante los beneficios en términos de reducción de la mortalidad cáncer específica o general. El propósito del presente artículo, es definir a la luz de la literatura médica reciente, la utilidad a nivel poblacional del cribado para cáncer de próstata basado en el antígeno prostático específico. Materiales y métodos Se realizó una revisión en los buscadores Pubmed, Embase y Lilacs utilizando los términos MesH "Prostatic neoplasms," "early detection of cancer," "mass screening," "prostate specific antigen," "digital rectal examination," "Outcome assesment (Health care)." Se filtró la búsqueda hacia estudios ejecutados en humanos, y/o metanálisis y revisiones sistemáticas publicados durante los últimos 10 años. Los abstracts fueron valorados por el grupo de autores e incluidos para análisis según su aporte al objetivo principal del estudio. Algunas referencias adicionales fueron añadidas dada su importancia clínica e histórica. Resultados Se identificaron 23 referencias con la estrategia de búsqueda, se excluyeron del análisis 9 referencias por no aportar datos relevantes para el presente artículo. Se incluyeron para revisión un total de 14 artículos. Discusión La tamización para cáncer de próstata con base en el antígeno específico de próstata sérico es una estrategia que permite aumentar la tasa de detección temprana de cáncer, sin embargo, se asocia a una importante tasa de detección de cáncer de próstata indolente y de sobretratamiento. Los resultados de la literatura evaluada son contradictorios con respecto al efecto que tiene la tamización sobre la mortalidad específica por cáncer, algunos estudios han revelado una disminución de ese ítem en los pacientes sometidos a tamización para cáncer de próstata. Los datos también son contundentes en demostrar que las estrategias de tamización no han impactado la supervivencia general en los grupos estudiados. Se esperan resultados de estudios que incluyan el armamento de estrategias disponibles para estimar el riesgo de cáncer de próstata (imágenes y/o nuevos marcadores tumorales) con el fin de mejorar la relación riesgo/beneficio de la estrategia de cribado para cáncer de próstata. Conclusiones La tamización para cáncer de próstata debe ser una estrategia para la detección temprana del cáncer que se usa de forma consensuada con cada paciente y que debe adaptarse al riesgo individual; el paciente a quien se le aplica el cribado debe entender los potenciales riesgos y beneficios de esta estrategia ya que los datos disponibles no permiten demostrar con alto nivel de evidencia, un beneficio clínico traducido en términos de reducción en la mortalidad del cáncer específica o general.

Introduction In the last decade, the prostate-specific antigen based screening for prostate cancer have evoque a lot of controversies on the basis of his risk ­ benefit ratio; there are controversial data about the impact of this strategy in the male cancer specific and general mortality. The aim of this article is to show the most recent findings and to define the utility of the population screening for early detection of prostate cancer. Material and Methods A literature review was performed in PubMed, Embase and Lilacs using the MeSH terms: "Prostatic neoplasms," "early detection of cancer," "mass screening," "prostate specific antigen," "digital rectal examination" and "Outcome assesment (Health care)" which was limited to scientific articles published in the past 10 years. The abstracts were evaluated and excluded if they were not related to primary aim of this article. Some references were included given their clinical relevance. Results 23 articles were retrieved, and after reviewing the abstracts, 9 articles were excluded as they were not related to our primary aim. The analysis was performed in 14 articles. Discussion The prostate-specific antigen based population screening has been associated with an early diagnosis of prostate cancer even, in a non significative clinical stage, and consequent overtreatment. The literature which was evaluated have controvesial outcomes on the cancer-specific mortality, however none of the articles evaluated shown a significant impact in male general mortality. In the overcoming years, we expect the results of some investigations which includes additional tools for the screening of prostate cancer (multiparametric prostate resonance imaging, new tumoral markers), to improve the risk-benefit of this strategy. Conclusions The population prostate cancer screening should be made in well-informed patients and shared based decision process. The urologist and patient should to know the potential benefits and risks of this strategy, because there is not high grade level of evidence which supports a significant effect of this strategy in male general and cancer-specific mortality.

De lo innato y lo adaptativo: premio Nobel de Medicina y Fisiología 2011: [Editorial] / From innate to the adaptive: Nobel Prize for Medicine or Physiology 2011: [Editorial]

La Real Academia de la Lengua Española define la palabra "innato" como algo connatural o propio a la naturaleza del ser viviente. A pesar de que los dos tipos de la respuesta inmunitaria se empezaron a configurar desde el principio el siglo XX, la inmunidad innata por muchos años parecía estar allí solamente acompañando la descripción y los avances de la inmunidad específica o adaptativa. El primer premio Nobel de Medicina de 1901 fue otorgado a Emil Adolf von Behring por sus estudios del suero inmune como tratamiento contra la difteria, trabajo que puso en contexto la funcionalidad de los anticuerpos. La inmunidad innata se impulsó gracias a los trabajos del zoólogo ruso Ilya Mechnikov, quien compartió con Paul Ehrlich el premio Nobel de Medicina de 1908; al primero le fue otorgado por sus estudios sobre la fagocitosis.

The Real Academia de la Lengua Española defines the word "innate" as something connatural or proper to the nature of the living being. Although the two types of immune response began to take shape at the beginning of the 20th century, innate immunity for many years seemed to be there only to accompany the description and advances of specific or adaptive immunity. The first Nobel Prize in Medicine in 1901 was awarded to Emil Adolf von Behring for his studies of immune serum as a treatment for diphtheria, work that put the functionality of antibodies into context. Innate immunity was boosted by the work of Russian zoologist Ilya Mechnikov, who shared the 1908 Nobel Prize in Medicine with Paul Ehrlich; the former was awarded for his studies on phagocytosis.