TDP-43 Cytoplasmic Translocation in the Skin Fibroblasts of ALS Patients

Diagnosis of ALS is based on clinical symptoms when motoneuron degeneration is significant. Therefore, new approaches for early diagnosis are needed. We aimed to assess if alterations in appearance and cellular localization of cutaneous TDP-43 may represent a biomarker for ALS. Skin biopsies from 64 subjects were analyzed: 44 ALS patients, 10 healthy controls (HC) and 10 neurological controls (NC) (Parkinson's disease and multiple sclerosis). TDP-43 immunoreactivity in epidermis and dermis was analyzed, as well as the percentage of cells with TDP-43 cytoplasmic localization. We detected a higher amount of TDP-43 in epidermis (p < 0.001) and in both layers of dermis (p < 0.001), as well as a higher percentage of TDP-43 cytoplasmic positive cells (p < 0.001) in the ALS group compared to HC and NC groups. Dermal cells containing TDP-43 were fibroblasts as identified by co-labeling against vimentin. ROC analyses (AUC 0.867, p < 0.001; CI 95% 0.800-0.935) showed that detection of 24.1% cells with cytoplasmic TDP-43 positivity in the dermis had 85% sensitivity and 80% specificity for detecting ALS. We have identified significantly increased TDP-43 levels in epidermis and in the cytoplasm of dermal cells of ALS patients. Our findings provide support for the use of TDP-43 in skin biopsies as a potential biomarker

International scientific research on venture capital: a bibliometric and mapping analysis from the period 1978–2020

The aim of this study is to explore the relevance of scientific production on venture capital using bibliometric and mapping tools.We performed a search in Scopus, involving any document published between 1978 and 2020. We used bibliometric indicators to explore documents production, dispersion, distribution, time of duplication, and annual growth, as Price’s law of scientific literature growth, Lotka’s law, the transient index, and the Bradford model. We also calculated the participation index of the different countries and institutions. Finally, we explored the co-occurrence and thematic networks for the most frequently used terms in venture capital research through bibliometric mapping.A total of 1,230 original articles were collected from the timeframe 1978–2020. The model confirms that Price’s law is not fulfilled. Scientific production was better adjusted to linear growth (r = 0.9290) than exponential (r = 0.9161). Literature on venture capital research has increased its growth in the last 43 years at a rate of 7.9% per year, with a production that doubles its size every 9.1 years. The transience index was 79.91%, which indicates that most of the scientific production is due to a lot of authors with a small number of publications on the research topic. Bradford´s law shows that the scientific production in this area is widely distributed in multiple journals, and Lotka’s law indicates that the author’s distribution is heavily concentrated on small producers. The United States of America (USA) and the University of Pennsylvania present the highest production, contributing 31.22% and 1.63% of the total production of research on venture capital.The venture capital task has undergone a linear growth, with a very high rate of transience, which indicates the presence of numerous authors who sporadically publish on this topic. No evidence of a saturation point was observed in the scientific production analyzed, which makes it possible to conclude that the research in venture capital will continue to be in demand by the scientific community.The aim of this study is to explore the relevance of scientific production on venture capital using bibliometric and mapping tools.We performed a search in Scopus, involving any document published between 1978 and 2020. We used bibliometric indicators to explore documents production, dispersion, distribution, time of duplication, and annual growth, as Price’s law of scientific literature growth, Lotka’s law, the transient index, and the Bradford model. We also calculated the participation index of the different countries and institutions. Finally, we explored the co-occurrence and thematic networks for the most frequently used terms in venture capital research through bibliometric mapping.A total of 1,230 original articles were collected from the timeframe 1978–2020. The model confirms that Price’s law is not fulfilled. Scientific production was better adjusted to linear growth (r = 0.9290) than exponential (r = 0.9161). Literature on venture capital research has increased its growth in the last 43 years at a rate of 7.9% per year, with a production that doubles its size every 9.1 years. The transience index was 79.91%, which indicates that most of the scientific production is due to a lot of authors with a small number of publications on the research topic. Bradford´s law shows that the scientific production in this area is widely distributed in multiple journals, and Lotka’s law indicates that the author’s distribution is heavily concentrated on small producers. The United States of America (USA) and the University of Pennsylvania present the highest production, contributing 31.22% and 1.63% of the total production of research on venture capital.The venture capital task has undergone a linear growth, with a very high rate of transience, which indicates the presence of numerous authors who sporadically publish on this topic. No evidence of a saturation point was observed in the scientific production analyzed, which makes it possible to conclude that the research in venture capital will continue to be in demand by the scientific community

Expectativas y percepciones de la madre respecto a su recién-nacido: aplicación del inventario de percepción neonatal de broussard

OBJECTIVES: To evaluate Broussard's Neonatal Perception Inventory (BPNI), an instrument to measure the mother's perception and expectations regarding her newborn infant at immediate postpartum and one month afterwards in primiparous and multiparous women. METHODS: Prospective cohort of 27 multiparous and 29 primiparous mothers of healthy newborn infants. In the second day postpartum, mothers were asked about the difficulties they thought that babies would offer regarding specific behaviors: crying, spitting, feeding, elimination, sleeping and predictability. Answers were rated in a 5-point scale. Next, mothers were questioned about their own babies regarding the same items. After 30 days, the mothers were questioned again about her perception of most babies and their own baby regarding the same items. The results were analyzed by repeated measures ANOVA considering the following main effects: time, group (primiparous and mul-tiparous), and subjects (mother's baby and most babies). RESULTS: Following birth, mothers expected their babies to have fewer difficulties in the daily activities than the ma-jority of the babies. These expectations were confirmed one month later for all items. There were no differences between primiparous and multiparous mothers. CONCLUSIONS: The Broussard's Neonatal Perception In-ventory was well understood and accepted by mothers and showed consistent results in this study. It can be used as a screening psychological tool to assess bonding between mothers and infants.OBJETIVOS: Analizar el Inventario de Percepción Neonatal de Broussard (BNPI - un instrumento que detecta las percepciones y expectativas maternas respecto a los hijos) enseguida al parto (T1) y con un mes de vida (T2), en puér-peras multíparas y primíparas. MÉTODOS: Coorte prospectiva con 27 multíparas y 29 primíparas madres de neonatos a término sanos. Se preguntó a la madre en T1 la dificultad que ella esperaba que la mayoría de los bebés tuviera respecto a llorar, alimentarse, regurgitar o vomitar, evacuar, dormir y tener una rutina. Las respuestas fueron marcadas en una escala de 5 puntos. Enseguida, se repitieron las preguntas respecto a su hijo recién-nacido. En T2, se preguntaba a la madre la dificultad que ella creía que la mayoría de los bebés y su propio hijo presentaban respecto a los mismos requisitos. El análisis estadístico utilizó ANOVA para medidas repetidas, teniendo en cuenta los siguientes efectos principales: tiempo (T1 y T2), grupo (primíparas y multíparas) y categoría (su bebé y la mayoría de los bebés). RESULTADOS: Enseguida al parto, las madres esperaban que sus hijos tuvieran menos dificultad en las actividades evaluadas que la mayoría de los bebés. Esta expectativa se confirmó con 30 días de vida para todos los comportamientos. No hubo diferencias entre primíparas y multíparas. CONCLUSIONES: El BNPI fue bien atendido y aceptado por las madres, mostrando resultados consistentes en este estudio. El instrumento puede ser útil para seleccionar pares madre-bebé con dificultades en el establecimiento de vínculo.OBJETIVOS: Analisar o Inventário de Percepção Neonatal de Broussard, um instrumento que detecta as percepções e expectativas maternas com respeito aos filhos logo após o parto (Tempo 1) e com um mês de vida (Tempo 2), em puérperas multíparas e primíparas. MÉTODOS: Coorte prospectiva com 27 multíparas e 29 primíparas mães de neonatos a termo saudáveis. Inquiriu-se à mãe no segundo dia pós-parto quanta dificuldade ela esperava que a maioria dos bebês tivesse em relação a chorar, alimentar, regurgitar ou vomitar, evacuar, dormir e ter uma rotina. As respostas foram marcadas em uma escala de 5 pontos. A seguir, repetiam-se as perguntas em relação ao seu filho recém-nascido. Após 30 dias, perguntava-se à mãe quanta dificuldade ela achava que a maioria dos bebês e seu próprio filho apresentavam em relação aos mesmos quesitos. A análise estatística utilizou ANOVA para medidas repe-tidas, considerando os seguintes efeitos principais: tempo, grupo (primíparas e multíparas) e categoria (seu bebê e a maioria dos bebês). RESULTADOS: Logo após o parto, as mães esperavam que seus filhos tivessem menos dificuldade nas atividades avalia-das do que a maioria dos bebês. Essa expectativa se confirmou com 30 dias de vida para todos os comportamentos. Não houve diferenças entre primíparas e multíparas. CONCLUSÕES: O Inventário de Percepção Neonatal de Broussard foi bem entendido e aceito pelas mães, mostrando resultados consistentes neste estudo. O instrumento pode ser útil para triar pares mãe-bebê com dificuldades no estabelecimento de vínculo.Universidade Federal de São Paulo (UNIFESP)Sociedade Brasileira de Psicanálise de São PauloHospital Geral de Itapecerica da SerraUNIFESPSciEL

Biodiversity of the "Pre Delta", National Park

Biodiversity can be understood by the means of two terms: richness and evenness. We study the biological richness of Pre Delta National Park (Entre Ríos, Argentina) on its floristic and ornithological, mastozoological and amphibian fauna. Pre-Delta National Park is located in the floodplain of Paraná River; almost all of its area is subject to annual flooding pulse. This main stress is source of environmental heterogeneity, which is reflected in its biodiversity. 372 plant species, distributed in 68 families represent much more of the diversity found in similar areas of this portion of the River. 12 species of Anuran in 4 families are little less than the expected number of species, but new species are constantly been added. 202 birds species in almost 50 families found represents more than the half of all the Province ornithofauna. Mammals is the less studied group, having 16 species with 9 more of highly probable presence. Paraná River act as biological corridor merging, at this latitude, Amazonic, Chacoan and Pampasic flora and fauna. We suspect that the area is still under-measured, as the species/area or specie/capture unit relation is still in its incremental portion.Fil: Aceñolaza, Pablo Gilberto. Provincia de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Universidad Autónoma de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción; Argentina. Universidad Nacional de Entre Ríos; ArgentinaFil: Povedano, Hernan A.. Provincia de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Universidad Autónoma de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción; ArgentinaFil: Manzano, Adriana Silvina. Provincia de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Universidad Autónoma de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción; ArgentinaFil: Muñoz, Juan de Dios. Universidad Nacional de Entre Ríos; ArgentinaFil: Areta, Juan Ignacio. Provincia de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Universidad Autónoma de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción; ArgentinaFil: Ronchi Virgolini, Ana Laura. Provincia de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Universidad Autónoma de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción; Argentin

Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by damage to the lungs and short telomeres

Pulmonary fibrosis is a fatal lung disease characterized by fibrotic foci and inflammatory infiltrates. Short telomeres can impair tissue regeneration and are found both in hereditary and sporadic cases. We show here that telomerase expression using AAV9 vectors shows therapeutic effects in a mouse model of pulmonary fibrosis owing to a low-dose bleomycin insult and short telomeres. AAV9 preferentially targets regenerative alveolar type II cells (ATII). AAV9-Tert-treated mice show improved lung function and lower inflammation and fibrosis at 1-3 weeks after viral treatment, and improvement or disappearance of the fibrosis at 8 weeks after treatment. AAV9-Tert treatment leads to longer telomeres and increased proliferation of ATII cells, as well as lower DNA damage, apoptosis, and senescence. Transcriptome analysis of ATII cells confirms downregulation of fibrosis and inflammation pathways. We provide a proof-of-principle that telomerase activation may represent an effective treatment for pulmonary fibrosis provoked or associated with short telomeres.We are indebted to D Megias for microscopy analysis, to J Mun˜ oz and F Garcı´a for hydroxiproline analysis as well as to CNIO Histopathological Unit. The research was funded by project SAF2013- 45111-R of Societal Changes Programme of the Spanish Ministry of Economics and Competitiveness (MINECO) co-financed through the European Fund of Regional Development (FEDER), Fundacio´n Botı´n and Banco Santander (Santander Universities Global Division) and Roche Extending the Innova- tion Network Program (EIN) Academia Partnering Programme.S

Facial onset sensory and motor neuronopathy: new cases, cognitive changes and pathophysiology

Purpose of review To improve our clinical understanding of facial onset sensory and motor neuronopathy (FOSMN). Recent findings We identified 29 new cases and 71 literature cases, resulting in a cohort of 100 patients with FOSMN. During follow-up, cognitive and behavioral changes became apparent in 8 patients, suggesting that changes within the spectrum of frontotemporal dementia (FTD) are a part of the natural history of FOSMN. Another new finding was chorea, seen in 6 cases. Despite reports of autoantibodies, there is no consistent evidence to suggest an autoimmune pathogenesis. Four of 6 autopsies had TAR DNA-binding protein (TDP) 43 pathology. Seven cases had genetic mutations associated with neurodegenerative diseases. Summary FOSMN is a rare disease with a highly characteristic onset and pattern of disease progression involving initial sensory disturbances, followed by bulbar weakness with a cranial to caudal spread of pathology. Although not conclusive, the balance of evidence suggests that FOSMN is most likely to be a TDP-43 proteinopathy within the amyotrophic lateral sclerosis–FTD spectrum

Aproximación Proteómica al síndrome de apneas-hipopneas del sueño

Comunicaciones a congreso

TRICALS: creating a highway toward a cure

A change in our current approach toward drug development is required to improve the likelihood of finding effective treatment for patients with amyotrophic lateral sclerosis (ALS). The aim of the Treatment Research Initiative to Cure ALS (TRICALS) is to extend the collective effort with industry and consolidate drug development paths. TRICALS has begun a series of meetings on how to best move the field forward collaboratively, thereby addressing five major topics in ALS clinical trials: (1) preclinical research, (2) biomarker development, (3) eligibility criteria, (4) efficacy endpoints and (5) innovative trial design. There is an appetite for ongoing discussions of these major topics in clinical trials between representatives from academia, patient advocacy groups, industry partners and funding bodies. Industry is open to fundamentally change drug development for ALS and shorten the time to effective therapy for patients by implementing promising innovations in biomarker development, trial design, and patient selection. There is however, a pressing need from all stakeholders for regulatory discussions and amendments of current guidelines to successfully adopt innovation in future clinical development lines

A first approach to assess the impact of bottom trawling over Vulnerable Marine Ecosystems on the High Seas of the Southwest Atlantic

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