Uso da citologia de impressão para a detecção de células de neoplasia escamosa da superfície ocular insuspeita em pterígios

Purpose: To evaluate the agreement between the methodologies of impression cytology (IC) and histopathology regarding epithelial lesions clinically diagnosed as pterygium and also regarding the detection of unsuspected and associated ocular surface squamous neoplasia (OSSN). Methods: Thirty-two Brazilian patients were included and IC was performed on all pterygia before excision. Histopathogical examination was considered the gold standard and was performed by two experienced ocular pathologists in which consensus existed regarding pterygia diagnosis. IC accuracy was assessed by sensitivity and specificity with a 95% confidence interval. Results: From the 32 primary lesions studied, histopathological examination confirmed the diagnosis of pterygium without atypical cells in 19 cases (60%) and showed unsuspected and associated OSSN cells in 13 cases (40%). IC demonstrated one false-negative and one false-positive result for atypia. Statistical analysis showed an estimated sensitivity of 92%, specificity of 94%, positive predictive value of 92%, and negative predictive value of 94%. Conclusion: IC demonstrated high agreement with histopathological analysis in the detection of atypical epithelial cells in unsuspected OSSN in Brazilian pterygia patients.Objetivo: Avaliar a concordância entre a citologia de impressão (CI) e os achados histopatológicos de lesões epiteliais clinicamente diagnosticadas como pterígio, no que tange a detecção de células de neoplasia escamosa da superfície ocular (NESO) insuspeita associada. Métodos: Trinta e dois pacientes brasileiros foram incluídos e a CI foi obtida de todos os pterígios antes da excisão. O exame histopatológico foi realizado por dois patologistas oculares experientes em consenso de opinião e considerado o padrão-ouro para o diagnóstico. A acurácia da CI foi avaliada pela sensibilidade e especificidade com intervalo de confiança de 95% Resultados: Das 32 lesões estudadas, o exame histopatológico confirmou o diagnóstico de pterígio sem atipia em 19 casos (60%) e mostrou células de NESO insuspeita associada em 13 espécimes (40%). A CI demonstrou um resultado falso-positivo e um falso-negativo para atipia. A análise estatística mostrou uma sensibilidade estimada de 92%, especificidade de 94%, valor preditivo positivo de 92% e valor preditivo negativo de 94%. Conclusão: A CI apresentou alta concordância com o estudo histopatológico na detecção de células epiteliais atípicas de NESO insuspeita em pterígios do Brasil.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM)UNIFESP, EPMSciEL

O que há na mente de um estrategista? O uso da modelagem de equações estruturais na compreensão do processo estratégico

This study is an attempt to understand how the dimensions of the strategy process (change, thinking and formation) are present in strategists’ minds. The methodology used is exploratory-descriptive. During the exploratory stage, we carried out desk research, which resulted in the development of a measurement tool for the strategy process. For the descriptive stage, we conducted a virtual survey of a sample of 109 executives of different companies. The data obtained were submitted to multivariate analysis (factor analysis and structural equations modeling). The factors that formed the studied dimensions were identified, confirming the existence of paradoxes in the strategy process. The dependence relations and the correlations observed were used as an input for the construction of a model for the strategy process.Este trabalho objetiva compreender como as dimensões do processo estratégico (Mudança, Pensamento e Formação) estão presentes nas mentes dos estrategistas. A metodologia utilizada nesta pesquisa é de caráter exploratório-descritivo. Durante a fase exploratória foi realizada uma desk research que culminou com o desenvolvimento de uma ferramenta de mensuração do processo estratégico. Para a fase descritiva, foi realizado um survey virtual composto por 109 executivos de diferentes empresas. Os dados obtidos foram submetidos a análises multivariadas (Análise Fatorial e Modelagem Estrutural de Equações). Os fatores formadores das dimensões investigadas foram identificados, confirmando desta forma, a existência de paradoxos no processo estratégico. As relações de dependência e as correlações observadas serviram, então, de insumo para a construção de um modelo do processo estratégico

The Photopic Negative Response: An Objective Measure of Retinal Ganglion Cell Function in Patients With Leber's Hereditary Optic Neuropathy

Purpose: The photopic negative response (PhNR) is a slow negative component of a flash photopic full-field ERG that has been shown to be specific for retinal ganglion cell (RGC) activity. Direct evaluation of RGC function is desirable in patients with Leber's hereditary optic neuropathy (LHON) in which the loss of central acuity can make it difficult to monitor patients with standard metrics. The purpose of this study was to evaluate the use of PhNR as an objective noninvasive clinical metric in LHON.Methods: Full-field photopic ERG recordings were collected in subjects with the mt.11778G>A/ND4 LHON mutation using a red on blue stimulus. The PhNR was identified using a computer-based automated detection system, and data were manually examined to remove movement artifacts.Results: The PhNR amplitude was compared between controls (n = 13), carriers (n = 17), and affected (n = 6). Mean PhNR amplitude decreased significantly across groups (P < 0.0001). Post hoc Tukey's test revealed a significant decrease in PhNR amplitude between carriers and controls (P < 0.05) and between carriers and affected (P < 0.01).Conclusions: We are able to demonstrate that the PhNR amplitude is significantly decreased in patients affected by LHON compared to carriers in a well-described pedigree. Surprisingly, there was also a decrease in PhNR in carriers, suggesting potential subclinical RGC dysfunction in some carriers. This is important in patients affected with LHON who typically have a dense central scotoma. The PhNR may be a useful objective outcome measure for future clinical trials

Estoques de carbono do solo e nas frações lábeis da matéria orgânica sob sistema agroflorestal em brejo de altitude pernambucano

Intense soil preparation and disturbance in crops, over time, reduces the quantity and quality of soil organic matter. Given this context, this work aimed to determine soil carbon stocks and labile fractions under agroforestry system (AFS) and toposequences in an altitude marsh, Taquaritinga do Norte, Pernambuco, Brazil. The study was carried out at the Yaguara farm, and the areas studied were native forest with 4.57 ha and coffee plantation in shade with native forest with 25.59 ha. Soil samples were collected in four trenches measuring 1.5 x 1.5 x 0.60 m, with a distance of 50 meters. Soils were collected at depths of 0–20, 20–40 and 40-60 cm, followed by chemical, physical and density analyzes to determine soil carbon stocks and labile fractions. The area with shaded coffee showed higher values ​​of soil carbon stocks at depths of 0-20 cm and 20-40 cm. At a depth of 40-60 cm, the AFS top toposequence showed the highest carbon stock with 11.73 Mg ha-1, followed by the area with native vegetation with 10.6 Mg ha-1, slope with 9.23 Mg ha-1 and pediment with 7.00 Mg ha-1. It was found that the top toposequence with shaded coffee exhibited a greater stock of labile carbon at depth 0-20 cm with a value of 1.06 Mg ha-1, followed by the bedding areas (SAF) with 0.88 Mg ha-1, native forest with 0.79 Mg ha-1 and slope with 0.67 g kg-1. However, the area of native vegetation showed the highest value of labile carbon at a depth of 40-60 cm. It was concluded that the area with shaded coffee in the top toposequence showed great capacity to increase total carbon stocks and labile carbon stocks of soil organic matter.O intenso preparo e revolvimento do solo em cultivos, com o tempo, reduz a quantidade e a qualidade da matéria orgânica do solo. Diante desse contexto, este trabalho teve como objetivo determinar os estoques de carbono do solo e frações lábeis sob sistema agroflorestal (SAF) e topossequências em brejo de altitude, em Taquaritinga do Norte, Pernambuco, Brasil. O estudo foi desenvolvido na fazenda Yaguara, e as áreas estudadas foram mata nativa com 4,57 ha e plantio de café sombreado com mata nativa com 25,59 ha. As amostras de solos foram coletadas em quatro trincheiras 1,5 x 1,5 x 0,60 m, com distância de 50 metros. Foram coletados solos nas profundidades de 0–20, 20–40 e 40-60 cm, seguido de análises químicas, físicas e densidade para determinação dos estoques de carbono no solo e frações lábeis. A área com café sombreado apresentou maiores valores de estoques de carbono no solo nas profundidades de 0-20 cm e 20-40 cm. Na profundidade de 40-60 cm, a topossequência de topo do SAF apresentou maior estoque de carbono com 11,73 Mg ha-1, seguido da área com vegetação nativa com 10,6 Mg ha-1 , encosta com 9,23 Mg ha-1 e pedimento com 7,00 Mg ha-1. Verificou-se que a topossequência de topo com café sombreado exibiu maior estoque de carbono lábil na profundidade 0-20 cm com o valor de 1,06 Mg ha-1, sucedido das áreas de pedimento (SAF) com 0,88 Mg ha-1, mata nativa com 0,79 Mg ha-1e encosta com 0,67 Mg ha-1. No entanto, a área de vegetação nativa apresentou o maior valor de carbono lábil na profundidade de 40-60 cm. Concluiu-se que a área com café sombreado na topossequência topo mostrou grande capacidade para elevar os estoques de carbono total e estoques de carbono lábil da matéria orgânica do solo

Promover os direitos das crianças - apostar na construção de melhores políticas públicas para a criança

Comunicação apresentada no 3º Encontro de Conhecimento e Cooperação, INA, Lisboa, 17 de setembro de 201

Pathological mitophagy disrupts mitochondrial homeostasis in Leber's hereditary optic neuropathy

Leber's hereditary optic neuropathy (LHON), a disease associated with a mitochondrial DNA mutation, is characterized by blindness due to degeneration of retinal ganglion cells (RGCs) and their axons, which form the optic nerve. We show that a sustained pathological autophagy and compartment-specific mitophagy activity affects LHON patient-derived cells and cybrids, as well as induced pluripotent-stem-cell-derived neurons. This is variably counterbalanced by compensatory mitobiogenesis. The aberrant quality control disrupts mitochondrial homeostasis as reflected by defective bioenergetics and excessive reactive oxygen species production, a stress phenotype that ultimately challenges cell viability by increasing the rate of apoptosis. We counteract this pathological mechanism by using autophagy regulators (clozapine and chloroquine) and redox modulators (idebenone), as well as genetically activating mitochondrial biogenesis (PGC1-α overexpression). This study substantially advances our understanding of LHON pathophysiology, providing an integrated paradigm for pathogenesis of mitochondrial diseases and druggable targets for therapy

Efficient mitochondrial biogenesis drives incomplete penetrance in Leber's hereditary optic neuropathy

Leber's hereditary optic neuropathy is a maternally inherited blinding disease caused as a result of homoplasmic point mutations in complex I subunit genes of mitochondrial DNA. It is characterized by incomplete penetrance, as only some mutation carriers become affected. Thus, the mitochondrial DNA mutation is necessary but not sufficient to cause optic neuropathy. Environmental triggers and genetic modifying factors have been considered to explain its variable penetrance. We measured the mitochondrial DNA copy number and mitochondrial mass indicators in blood cells from affected and carrier individuals, screening three large pedigrees and 39 independently collected smaller families with Leber's hereditary optic neuropathy, as well as muscle biopsies and cells isolated by laser capturing from post-mortem specimens of retina and optic nerves, the latter being the disease targets. We show that unaffected mutation carriers have a significantly higher mitochondrial DNA copy number and mitochondrial mass compared with their affected relatives and control individuals. Comparative studies of fibroblasts from affected, carriers and controls, under different paradigms of metabolic demand, show that carriers display the highest capacity for activating mitochondrial biogenesis. Therefore we postulate that the increased mitochondrial biogenesis in carriers may overcome some of the pathogenic effect of mitochondrial DNA mutations. Screening of a few selected genetic variants in candidate genes involved in mitochondrial biogenesis failed to reveal any significant association. Our study provides a valuable mechanism to explain variability of penetrance in Leber's hereditary optic neuropathy and clues for high throughput genetic screening to identify the nuclear modifying gene(s), opening an avenue to develop predictive genetic tests on disease risk and therapeutic strategies.TelethonAssociazione Serena Talarico per i giovani nel mondo and Fondazione Giuseppe Tomasello O.N.L.U.S.Mitocon OnlusResearch to Prevent BlindnessInternational Foundation for Optic Nerve Diseases (IFOND)Struggling Within Leber'sPoincenot FamilyEierman FoundationNational Eye InstituteUniv Rome, Dept Radiol Oncol & Pathol, Rome, ItalyUniv Bologna, Dept Biomed & NeuroMotor Sci DIBINEM, Bologna, ItalyUniv Bari, Dept Biosci Biotechnol & Biopharmaceut, Bari, ItalyBellaria Hosp, IRCCS Ist Sci Neurol Bologna, I-40139 Bologna, ItalyUSC, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA USAUSC, Keck Sch Med, Dept Neurosurg, Los Angeles, CA USAUniv Trieste, Dept Reprod Sci Dev & Publ Hlth, Trieste, ItalyUniv Trieste, IRCCS Burlo Garofolo Children Hosp, Trieste, ItalyNewcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, EnglandFdn Ist Neurol Carlo Besta IRCCS, Unit Mol Neurogenet, Milan, ItalyMRC Mitochondrial Biol Unit, Cambridge, EnglandFed Univ São Paulo UNIFESP, Dept Ophthalmol, São Paulo, BrazilUniv São Paulo, Inst Psychol, Dept Expt Psychol, São Paulo, BrazilStudio Oculist dAzeglio, Bologna, ItalyOsped San Giovanni Evangelista, Tivoli, ItalyAzienda Osped San Camillo Forlanini, Rome, ItalyUniv Rome, Dipartimento Metodi & Modelli Econ Finanza & Terr, Rome, ItalyUniv Rome, Dept Mol Med, Rome, ItalyFed Univ São Paulo UNIFESP, Dept Ophthalmol, São Paulo, BrazilTelethon: GGP06233Telethon: GGP11182Telethon: GPP10005National Eye Institute: EY03040Web of Scienc

Geographic patterns of tree dispersal modes in Amazonia and their ecological correlates

Aim: To investigate the geographic patterns and ecological correlates in the geographic distribution of the most common tree dispersal modes in Amazonia (endozoochory, synzoochory, anemochory and hydrochory). We examined if the proportional abundance of these dispersal modes could be explained by the availability of dispersal agents (disperser-availability hypothesis) and/or the availability of resources for constructing zoochorous fruits (resource-availability hypothesis). Time period: Tree-inventory plots established between 1934 and 2019. Major taxa studied: Trees with a diameter at breast height (DBH) ≥ 9.55 cm. Location: Amazonia, here defined as the lowland rain forests of the Amazon River basin and the Guiana Shield. Methods: We assigned dispersal modes to a total of 5433 species and morphospecies within 1877 tree-inventory plots across terra-firme, seasonally flooded, and permanently flooded forests. We investigated geographic patterns in the proportional abundance of dispersal modes. We performed an abundance-weighted mean pairwise distance (MPD) test and fit generalized linear models (GLMs) to explain the geographic distribution of dispersal modes. Results: Anemochory was significantly, positively associated with mean annual wind speed, and hydrochory was significantly higher in flooded forests. Dispersal modes did not consistently show significant associations with the availability of resources for constructing zoochorous fruits. A lower dissimilarity in dispersal modes, resulting from a higher dominance of endozoochory, occurred in terra-firme forests (excluding podzols) compared to flooded forests. Main conclusions: The disperser-availability hypothesis was well supported for abiotic dispersal modes (anemochory and hydrochory). The availability of resources for constructing zoochorous fruits seems an unlikely explanation for the distribution of dispersal modes in Amazonia. The association between frugivores and the proportional abundance of zoochory requires further research, as tree recruitment not only depends on dispersal vectors but also on conditions that favour or limit seedling recruitment across forest types