Strong Upregulation of Inflammatory Genes Accompanies Photoreceptor Demise in Canine Models of Retinal Degeneration

We have analyzed the complex pattern of the inflammatory response in early-onset canine models of human retinitis pigmentosa, rcd1, xlpra2 and erd, as well as late-onset xlpra1, in comparative manner. The time course of immune response genes and proteins expression was examined along the timeline of photoreceptors degeneration. Gene expression analysis of the early-onset models prior to and after the peak of photoreceptors death identified the involvement of multiple immune response genes including those encoding constituents of the NLRP3 inflammasome, its substrates, pro-IL1B, pro-IL18, and common components of IL1B, IL18 and TLR4 pathways. Out of two activated caspase-1 cleavage products, IL1B and IL18, only IL1B was detected in rcd1 and xlpra2 while precursor IL18 remained unprocessed in the same protein extract highlighting prominence of IL1B pathway. An overall immune response was most prominent in rcd1 followed by xlpra2 and least prominent in erd. Noticeably, in rcd1 and xlpra2, but not in erd, early induction of the immune response was accompanied by sustained intraretinal migration and activation of retinal microglia. Lastly, delayed activation of the anti-inflammatory factors in all early-onset models was insufficient to counterbalance rapidly progressing inflammation. In contrast to early-onset models, in late-onset xlpra1 retinas a subset of the pro-inflammatory genes was highly upregulated long before any disease-related structural changes occurred, but was counterbalanced by an adequate anti-inflammatory response. Results point out to upregulated immune response accompanying disease progression in animal models of retinal degeneration, and to potential benefits of early anti-inflammatory therapy

Molecular Studies of Phenotype Variation in Canine RPGR-XLPRA1

Purpose: Canine X-linked progressive retinal atrophy 1 (XLPRA1) caused by a mutation in retinitis pigmentosa (RP) GTPase regulator (RPGR) exon ORF15 showed significant variability in disease onset in a colony of dogs that all inherited the same mutant X chromosome. Defective protein trafficking has been detected in XLPRA1 before any discernible degeneration of the photoreceptors. We hypothesized that the severity of the photoreceptor degeneration in affected dogs may be associated with defects in genes involved in ciliary trafficking. To this end, we examined six genes as potential disease modifiers. We also examined the expression levels of 24 genes involved in ciliary trafficking (seven), visual pathway (five), neuronal maintenance genes (six), and cellular stress response (six) to evaluate their possible involvement in early stages of the disease. Methods: Samples from a pedigree derived from a single XLPRA1-affected male dog outcrossed to unrelated healthy mix-bred or purebred females were used for immunohistochemistry (IHC), western blot, mutational and haplotype analysis, and gene expression (GE). Cell-specific markers were used to examine retinal remodeling in the disease. Single nucleotide polymorphisms (SNPs) spanning the entire RPGR interacting and protein trafficking genes (RAB8A, RPGRIP1L, CEP290, CC2D2A, DFNB31, and RAB11B) were genotyped in the pedigree. Quantitative real-time PCR (qRT-PCR) was used to examine the expression of a total of 24 genes, including the six genes listed. Results: Examination of cryosections from XLPRA1-affected animals of similar age (3–4 years) with different disease severity phenotype revealed mislocalization of opsins and upregulation of the Müller cell gliosis marker GFAP. Four to ten haplotypes per gene were identified in RAB8A, RPGRIP1L, CEP290, CC2D2A, DFNB31, and RAB11B for further assessment as potential genetic modifiers of XLPRA1. No correlation was found between the haplotypes and disease severity. During mutational analysis, several new variants, including a single intronic mutation in RAB8A and three mutations in exon 3 of DFNB31were described (c.970G\u3eA (V324I), c.978T\u3eC (G326=), and c.985G\u3eA (A329T)). Expression analysis of stress response genes in 16-week-old predisease XLPRA1 retinas revealed upregulation of GFAP but not HSPA5, DDIT3, HSPA4, HSP90B1, or HIF1A. Western blot analysis confirmed GFAP upregulation. In the same predisease group, no significant differences were found in the expression of 18 selected genes (RHO, OPN1LW, OPN1MW, RLBP1, RPGRORF15, RAB8A, RPGRIP1L, CEP290, CC2D2A, DFNB31, RAB11B, CRX, RCVRN, PVALB, CALB1, FGFR1, NTRK2, and NTRK3) involved in neuronal function. Conclusions: Lack of association between haplotypes of RAB8A, RPGRIP1L, CEP290, CC2D2A, DFNB31, and RAB11B and the disease phenotype suggests that these genes are not genetic modifiers of XLPRA1. Upregulation of GFAP, an established indicator of the Müller cell gliosis, manifests as an important early feature of the disease

ESTIMACIÓN DE LA PÉRDIDA ESPERADA DE LA CARTERA DE CRÉDITO DE UNA SOCIEDAD FINANCIERA DE OBJETO MÚLTIPLE ENTIDAD NO REGULADA EN LA CIUDAD DE TOLUCA, ESTADO DE MÉXICO EN EL PERIODO ENERO 2014 – JULIO 2015

Es importante mencionar que con el contenido de esta investigación, se pretende dar respuesta a los siguientes cuestionamientos que se plantearon: ¿Cómo será el desempeño del modelo para estimar la pérdida esperada de la SOFOM E.N.R? ¿Es posible establecer los factores que permitan la estimación de la pérdida esperada? ¿Cómo se puede estimar la probabilidad de incumplimiento de la entidad? ¿Qué variables socio-demográficas, financieras y crediticias podrían describir el incumplimiento? Este trabajo de investigación se compone de cuatro capítulos que se resumen a continuación: En el capítulo uno, se revisará de manera general los antecedentes del sistema financiero y el proceso de cómo se consolidó a través del sistema bancario. También se conceptualizarán las principales instituciones de éste y puntualmente de la SOFOM E.N.R. así como su definición, marco legal y normativo. En este capítulo también se presentará la evidencia empírica que dio pie a este estudio. En el capítulo dos se darán a conocer los principales riesgos financieros, particularmente, el riesgo de crédito así como las metodologías para su medición y las principales metodologías para calcular la probabilidad de incumplimiento. En el capítulo tres se describe la estimación de la pérdida esperada, se dará un descripción de la cartera de crédito, se presentarán las estimaciones de la exposición al 4 Loss Given Default 5 Exposure At Defaul 11 riesgo, severidad de la pérdida y probabilidad de incumplimiento, así como se darán a conocer los principales resultados. En el cuarto capítulo se presentarán las conclusiones de los resultados obtenidos

Electrocatalytic self-assembled multilayer structures based on thiolated Fc-DAB dendrimers: Determination of heavy metal ions by enzymatic inhibition

The development of sensitive and rapid inhibition-based biosensors for monitoring trace levels of heavy metals such as lead and copper ions in environmental samples is of high interest. In this work, we describe the fabrication of HRP sensitive peroxide biosensors based on ferrocenyl thiolated DAB dendrimers as bonding-layer between electrodeposited and colloidal gold nanoparticles and compare their electrocatalytic properties with those of thiolated DAB homologues. The complete electrochemical, kinetic and analytical characterization of these new heavy metals’ inhibition-biosensors are investigate

Variabilities in Retinal Function and Structure in a Canine Model of Cone-Rod Dystrophy Associated With RPGRIP1 Support Multigenic Etiology

Defects in the cilia gene RPGRIP1 cause Leber congenital amaurosis and cone-rod dystrophy in humans. A form of canine cone-rod dystrophy (cord1) was originally associated with a homozygous insertion in RPGRIP1 (RPGRIP1ins/ins) as the primary disease locus while a homozygous deletion in MAP9(MAP9del/del) was later identified as a modifier associated with the early onset form. However, we find further variability in cone electroretinograms (ERGs) ranging from normal to absent in an extended RPGRIP1ins/ins canine colony, irrespective of the MAP9 genotype. Ophthalmoscopically, cone ERGabsentRPGRIP1ins/ins eyes show discolouration of the tapetal fundus with varying onset and disease progression, while sd-OCT reveals atrophic changes. Despite marked changes in cone ERG and retinal morphology, photopic vision-guided behaviour is comparable between normal and cone ERGabsentRPGRIP1ins/ins littermates. Cone morphology of the dogs lacking cone ERG are truncated with shortened outer and inner segments. Immunohistochemically, cone ERGabsentRPGRIP1ins/ins retinas have extensive L/M-opsin mislocalization, lack CNGB3 labelling in the L/M-cones, and lack GC1 in all cones. Our results indicate that cord1 is a multigenic disease in which mutations in neither RPGRIP1 nor MAP9 alone lead to visual deficits, and additional gene(s) contribute to cone-specific functional and morphologic defects

ULTRASONOGRAFÍA EN EL DIAGNÓSTICO DE LA HIPERPLASIA BENIGNA PROSTÁTICA: APORTES A LA PRÁCTICA IMAGENOLÓGICA

La hiperplasia o adenoma, es una afección benigna por el crecimiento excesivo del tejido de la próstata, que presiona la uretra y la vejiga, bloquea así el flujo de la orina creando síntomas incómodos en el tracto urinario inferior. Se pueden utilizar muchos métodos imagenológicos o uroendoscópicos para estimar el volumen de la próstata y diagnosticar la hiperplasia prostática. La ecografía transabdominal (TAUS) ha sido muy utilizada para la estimación del volumen de la próstata, aunque su uso sobreestima el volumen de la próstata. Sin embargo, la ecografía transrectal (TRUS) se considera actualmente el estándar de oro para la estimación del volumen prostático. El objetivo de la presente investigación está en aportar evidencia para el correcto diagnóstico ecográfico de hiperplasia benigna prostática

A procedure for assessment of the reducing capacity of plants-derived beverages based on the formation of the FeII/2,2’-bipyridine complex

An alternative spectrophotometric ferric reducing activity power (FRAP) method for quantification of total reducing capacity (TRC) was developed. The method is based on the reduction of FeIII to FeII by antioxidant compounds containing 2,2’-bipyridine (bipy) in aqueous solution. Absorbance values recorded at 521 nm, characteristic of the Fe(bipy)3 2+ complex formed, were used to determine the TRC of some plants-derived beverages. For the teas samples, the TRC values obtained with the proposed method and cupric reducing antioxidant capacity (CUPRAC) reagent had an excellent agreement (adjusted correlation coefficient (r2) = 0.951). Concerning herbs samples, the TRC values obtained with the proposed FRAP method correlated very well with values obtained using the 2,2’-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS•+) method (adjusted r2 = 0.975). It can be inferred from these results that other beverages derived from plants (e.g., beers, wines, and fruits juices) could also be analyzed with this new FRAP assay. In addition, the reducing capacity of 21 phenolic derivatives was determined with the proposed method in order to elucidate their structure-reactivity relationship. As expected, the phenolic derivative structure changes greatly the TRC values obtained with this proposed FRAP assay. © 2019 Sociedade Brasileira de Química

INOVAÇÃO ABERTA PARA UMA EMPRESA PÚBLICA - UTILIZANDO REFLEXÕES E CONEXÕES SOBRE A OBRA AMERICAN PROMETHEUS: THE TRIUMPH AND TRAGEDY OF JULIUS ROBERT OPPENHEIMER E O FILME OPPENHEIMER

A inovação aberta tem sido um desafio para as organizações modernas. Devido aos rápidos avanços da tecnologia da informação e das alterações nos ambientes de negócios, empresas têm se debruçado para encontrar a porta de entradas e saídas para a inovação, em seus campos de atuação. Empresas como os Correios, com 360 anos de existência, possuem muitas barreiras para deixar fluir a inovação aberta e pode aprender muito com o laboratório “Los Álamos” utilizado para desenvolver a tecnologia atômica. Nesse sentido, a questão de pesquisa é como analisar o processo de inovação aberta para os Correios, a partir de uma reflexão do laboratório “Los Álamos”, contido na obra American Prometheus: The Triumph and Tragedy of Julius Robert Oppenheimer e no filme Oppenheimer? O objetivo é analisar as questões conceituais e centrais da inovação aberta e do desafio do laboratório “Los Álamos” contido no livro American Prometheus: The Triumph and Tragedy of Julius Robert Oppenheimer e no filme Oppenheimer, visando refletir sobre esse fenômeno e como ele pode auxiliar na compreensão dos processos de inovação aberta para uma organização tradicional como os Correios. A pesquisa possui análise descritiva e qualitativa e se assenta sobre a análise reflexiva/comparativa. Destacando-se as principais reflexões se chega à conclusão de que inovação aberta em empresas públicas como os Correios é uma tarefa difícil, pelo grau de institucionalização existente. Que a inovação não é um processo de “moda” e nem acontece por acaso. Precisa estar ligada a estratégia da empresa e ser coordenada por um organismo único que irá direcionar programas, projeto, ações e recursos financeiros e humanos, visando integrar sistemicamente a estratégia de inovação e o gerenciamento da inovação

Instrumentos utilizados por fisioterapeutas para a avaliação de pacientes com sequelas de acidente vascular cerebral / Instruments used by physiotherapists for the evaluation of patients with stroke sequelae

O Acidente Vascular Cerebral (AVC) é uma doença neurológica, causada pela interrupção da circulação sanguínea cerebral, por meio de uma hemorragia ou uma isquemia. Essa interrupção resulta em falta de oxigênio para o cérebro, o que gera lesões cerebrais e perda da função da região do corpo que é controlada pela área do cérebro que foi acometida. As complicações do AVC podem desencadear muitas sequelas em partes sensitivas, motoras e cognitivas. Diante disso é muito importante a realização de um processo de reabilitação, no qual é necessária uma avaliação precisa do fisioterapeuta responsável. Tal avaliação deve envolver anamnese e exame físico, combinado a instrumentos como testes, escalas e questionários, pois eles fornecem dados para o planejamento e priorização do tratamento, e também para monitorar a evolução desses pacientes, permitindo ainda identificar se há necessidade de reajuste da intervenção e contribuindo para o prognóstico.   Objetivo: Analisar instrumentos utilizados por fisioterapeutas para a avaliação de pacientes com sequelas de AVC. Métodos: Este estudo foi elaborado a partir de uma revisão da literatura nas bases de dados PubMed e Scielo, de caráter exploratório, no período de 2005 a 2020. Foram utilizados os seguintes descritores: “Avaliação”, “Acidente vascular encefálico” e “Fisioterapia”, relacionados também com seus sinônimos e termos semelhantes em inglês “Measurement”, “Stroke” e “Physiotherapy”. Resultados: Foram encontrados nas bases de dados um total de 201 artigos, dos quais 22 foram selecionados e continham os desfechos de interesse desta revisão. Conclusão: Os testes, escalas e questionários utilizados para avaliar indivíduos com sequelas de AVC são confiáveis, validados e alguns deles podem ser instrumentos indicadores da gravidade de comprometimentos motores, sensitivos e cognitivos. Isso facilita e incentiva fisioterapeutas a utilizarem-nos em sua prática clínica, permitindo que esses profissionais tenham mais segurança para o planejamento do tratamento, maior capacidade para ajustes nas medidas de intervenção, assim como maior controle e precisão da evolução desses pacientes