670 nm laser light and EGCG complementarily reduce amyloid-β aggregates in human neuroblastoma cells: basis for treatment of Alzheimer's disease?

Objective: The aim of the present study is to present the results of in vitro experiments with possible relevance in the treatment of Alzheimer's disease (AD). Background Data: Despite intensive research efforts, there is no treatment for AD. One root cause of AD is the extra- and intracellular deposition of amyloid-beta (A{beta}) fibrils in the brain. Recently, it was shown that extracellular A{beta} can enter brain cells, resulting in neurotoxicity. Methods: After internalization of A{beta}(42) into human neuroblastoma (SH-EP) cells, they were irradiated with moderately intense 670-nm laser light (1000 Wm(-2)) and/or treated with epigallocatechin gallate (EGCG). Results: In irradiated cells, A{beta}(42) aggregate amounts were significantly lower than in nonirradiated cells. Likewise, in EGCG-treated cells, A{beta}(42) aggregate amounts were significantly lower than in non-EGCG-treated cells. Except for the cells simultaneously laden with A{beta}(42) and EGCG, there was a significant increase in cell numbers in response to laser irradiation. EGCG alone had no effect on cell proliferation. Laser irradiation significantly increased ATP levels in A{beta}(42)-free cells, when compared to nonirradiated cells. Laser-induced clearance of Aβ(42) aggregates occurred at the expense of cellular ATP. Conclusions: Irradiation with moderate levels of 670-nm light and EGCG supplementation complementarily reduces A{beta} aggregates in SH-EP cells. Transcranial penetration of moderate levels of red to near-infrared (NIR) light has already been amply exploited in the treatment of patients with acute stroke; the blood-brain barrier (BBB) penetration of EGCG has been demonstrated in animals. We hope that our approach will inspire a practical therapy for AD

A dark scenario for Cerrado plant species: effects of future climate, land-use, and protected areas ineffectiveness

Aim: The anthropogenic climate change and land-use change are considered two of the main factors that are altering biodiversity at the global scale. An evaluation that combined both factors can be relevant to detect which species could be the most vulnerable and reveal the regions of highest stability or susceptibility to biodiversity.We aimed to (i) assess the effect of the climate change and land-use on the distribution of the Cerrado plant species for different countries where it occurs, (ii) evaluate the efficiency of the current protected areas (PAs) network to safeguards species under different greenhouse gas (GHG) emissions and land-use and (iii) estimate the vulnerability of species caused by protection efficiency and habitat loss.Location: Bolivia, Brazil, and ParaguayMethods: We modeled the distribution of 1,553 plant species of Cerrado and evaluated species range loss caused by present and future land-use and two GHG for 2050 and 2080. We assessed the species vulnerability combining the representativeness of a species´ distribution within conservation units and the loss of species range outside PAs.Results: We found that climate change and land-use will cause great damage to Cerrado flora by 2050 and 2080, even under optimistic conditions. Unfortunately, the greatest intensity and extent of land-use will have to overcome on the regions where the greatest richness will be harbored. The conservation of the species will be seriously affected since the PAs network is not as efficient in safeguarding them under current or future conditions. Main conclusions: The low level of protection together with the losses caused by the advance of the agricultural frontier will lead to most species being highly vulnerable. Due to the climate and land-use, effects showed different interactions in each country, conservation strategies should be implemented at transboundary and national levels.Fil: Velazco, Santiago José Elías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Puerto Iguazú | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Puerto Iguazú; Argentina. Universidade Federal do Paraná; BrasilFil: Villalobos, Fabricio. Instituto de Ecología; México. Universidade Federal de Goiás; BrasilFil: Galvao, Franklin. Universidade Federal do Paraná; BrasilFil: de Marco Junior, Paulo. Universidade Federal de Goiás; Brasi

Estrés, ansiedad y depresión en estudiantes secundarios de la ciudad de Santa Rosa del Aguaray, Departamento de San Pedro, 2016

Introducción: En este estudio interesa investigar los niveles de estrés, ansiedad y depresión que tiene una población de estudiantes secundarios. Creemos importante estudiar esta temática, en particular porque al tratarse de preuniversitarios debe darse especial énfasis a la detección e intervención precoz sobre situaciones que podrían afectar su desarrollo personal, académico, familiar y social. Materiales y métodos: Estudio observacional, descriptivo, con corte transversal y muestreo no probabilístico a criterio, realizado en estudiantes de educación media del Colegio Nacional “Santa Rosa”, del Departamento de San Pedro. Para medir estrés, ansiedad y depresión, se utilizó el DASS-21, que consta de 21 ítems. Resultados: Se evidenció la existencia de al menos cierto nivel del estrés en el 43,5% de los estudiantes entrevistados, siendo de nivel extremo en 8,7% de los participantes. Se reportó algún grado de ansiedad en por lo menos el 71,7%, y algún grado de depresión en al menos 52,2% de los participantes. Discusión: Si bien los niveles de estrés encontrados en la presente investigación son menores a los reportados en la bibliografía, los valores de ansiedad y depresión superan los reportados por otros estudios en población similar. La investigación sobre los niveles de estrés, ansiedad y depresión en estudiantes preuniversitarios es un tema actual e innovador, que busca encontrar soluciones efectivas para hacer frente a estas condiciones que repercuten negativamente en la vida de los estudiantes

Green tea halts progression of cardiac transthyretin amyloidosis: an observational report

BACKGROUND: Treatment options in patients with amyloidotic transthyretin (ATTR) cardiomyopathy are limited. Epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea (GT), inhibits fibril formation from several amyloidogenic proteins in vitro. Thus, it might also halt progression of TTR amyloidosis. This is a single-center observational report on the effects of GT consumption in patients with ATTR cardiomopathy. METHODS: 19 patients with ATTR cardiomyopathy were evaluated by standard blood tests, echocardiography, and cardiac MRI (n = 9) before and after consumption of GT and/or green tea extracts (GTE) for 12 months. RESULTS: Five patients were not followed up for reasons of death (n = 2), discontinuation of GT/GTE consumption (n = 2), and heart transplantation (n = 1). After 12 months no increase of left ventricular (LV) wall thickness and LV myocardial mass was observed by echocardiography. In the subgroup of patients evaluated by cardiac MRI a mean decrease of LV myocardial mass (-12.5 %) was detected in all patients. This was accompanied by an increase of mean mitral annular systolic velocity of 9 % in all 14 patients. Total cholesterol (191.9 ± 8.9 vs. 172.7 ± 9.4 mg/dL; p < 0.01) and LDL cholesterol (105.8 ± 7.6 vs. 89.5 ± 8.0 mg/dL; p < 0.01) decreased significantly during the observational period. No serious adverse effects were reported by any of the participants. CONCLUSIONS: Our observation suggests an inhibitory effect of GT and/or GTE on the progression of cardiac amyloidosis. We propose a randomized placebo-controlled investigation to confirm our observation

Assessment of Daily Life Physical Activities in Pulmonary Arterial Hypertension

Background: In pulmonary arterial hypertension (PAH), the six-minute walk test (6MWT) is believed to be representative of patient’s daily life physical activities (DLPA). Whether DLPA are decreased in PAH and whether the 6MWT is representative of patient’s DL PA remain unknown. Methods: 15 patients with idiopathic PAH (IPAH) and 10 patients with PAH associated with limited systemic sclerosis (PAH-SSc) were matched with 15 healthy control subjects and 10 patients with limited systemic sclerosis without PAH. Each subject completed a 6MWT. The mean number of daily steps and the mean energy expenditure and duration of physical activities.3 METs were assessed with a physical activity monitor for seven consecutive days and used as markers of DLPA. Results: The mean number of daily steps and the mean daily energy expenditure and duration of physical activities.3 METs were all reduced in PAH patients compared to their controls (all p,0.05). The mean number of daily steps correlated with the 6MWT distance for both IPAH and PAH-SSc patients (r = 0.76, p,0.01 and r = 0.85, p,0.01), respectively. Conclusion: DLPA are decreased in PAH and correlate with the 6MWT distance. Functional exercise capacity may thus be a useful surrogate of DL PA in PAH

Short term effects of exercise training on exercise capacity and quality of life in patients with pulmonary arterial hypertension: protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Advances in the understanding and management of pulmonary arterial hypertension have enabled earlier diagnosis and improved prognosis. However, despite best available therapy, symptoms of exertional dyspnoea and fatigue are commonly reported and result in a reduced capacity to perform daily activities and impaired quality of life. Exercise training has demonstrated efficacy in individuals with other respiratory and cardiovascular diseases. Historically, however, exercise training has not been utilised as a form of therapy in pulmonary arterial hypertension due to the perceived risk of sudden cardiac death and the theoretical possibility that exercise would lead to worsening pulmonary vascular haemodynamics and deterioration in right heart function. Now, with the advances in pharmaceutical management, determining the safety and benefits of exercise training in this population has become more relevant. Only three studies of supervised exercise training in pulmonary arterial hypertension have been published. These studies demonstrated improvements in exercise capacity and quality of life, in the absence of adverse events or clinical deterioration. However, these studies have not utilised an outpatient-based, whole body exercise training program, the most common format for exercise programs within Australia. It is uncertain whether this form of training is beneficial and capable of producing sustained benefits in exercise capacity and quality of life in this population.</p> <p>Design/Methods</p> <p>This randomised controlled trial will determine whether a 12 week, outpatient-based, supervised, whole body exercise training program, followed by a home-based exercise program, is safe and improves exercise capacity and quality of life in individuals with pulmonary arterial hypertension. This study aims to recruit 34 subjects who will be randomly allocated to the exercise group (supervised exercise training 3 times a week for 12 weeks, followed by 3 sessions per week of home exercise for 12 weeks) or the control group (usual medical care). Subjects will be assessed at baseline, 12 weeks and 24 weeks.</p> <p>Discussion</p> <p>This study will determine whether outpatient-based, whole body exercise training is beneficial and safe in individuals with pulmonary arterial hypertension. Additionally, this study will contribute to clinical practice guidelines for this patient population.</p> <p>Trial registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12609000502235.aspx">ACTRN12609000502235</a></p

Atlas of the clinical genetics of human dilated cardiomyopathy

AIM: Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort. METHODS AND RESULTS: In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes. CONCLUSIONS: This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM