Accumulation of Exogenous Amyloid-Beta Peptide in Hippocampal Mitochondria Causes Their Dysfunction: A Protective Role for Melatonin

Amyloid-beta (Aβ) pathology is related to mitochondrial dysfunction accompanied by energy reduction and an elevated production of reactive oxygen species (ROS). Monomers and oligomers of Aβ have been found inside mitochondria where they accumulate in a time-dependent manner as demonstrated in transgenic mice and in Alzheimer's disease (AD) brain. We hypothesize that the internalization of extracellular Aβ aggregates is the major cause of mitochondrial damage and here we report that following the injection of fibrillar Aβ into the hippocampus, there is severe axonal damage which is accompanied by the entrance of Aβ into the cell. Thereafter, Aβ appears in mitochondria where it is linked to alterations in the ionic gradient across the inner mitochondrial membrane. This effect is accompanied by disruption of subcellular structure, oxidative stress, and a significant reduction in both the respiratory control ratio and in the hydrolytic activity of ATPase. Orally administrated melatonin reduced oxidative stress, improved the mitochondrial respiratory control ratio, and ameliorated the energy imbalance

Cintilografia de perfusão miocárdica na detecção da isquemia silenciosa em pacientes diabéticos assintomáticos

OBJECTIVE: This study was aimed to evaluate myocardial perfusion in asymptomatic patients with type 1 (DM1) and type 2 diabetes mellitus (DM2) without previous diagnoses of coronary artery disease (CAD) or cerebral infarction. MATERIALS AND METHODS: Fifty-nine consecutive asymptomatic patients (16 DM1, 43 DM2) underwent myocardial perfusion scintigraphy with 99mTc-sestamibi (MPS). They were evaluated for body mass index, metabolic control of DM, type of therapy, systemic arterial hypertension, dyslipidemia, nephropathy, retinopathy, peripheral neuropathy, smoking, and familial history of CAD. RESULTS: MPS was abnormal in 15 patients (25.4%): 12 (20.3%) with perfusion abnormalities, and 3 with isolated left ventricular dysfunction. The strongest predictors for abnormal myocardial perfusion were: age 60 years and above (p = 0.017; odds ratio [OR] = 6.0), peripheral neuropathy (p = 0.028; OR = 6.1), nephropathy (p = 0.031; OR = 5.6), and stress ECG positive for ischemia (p = 0.049; OR = 4.08). CONCLUSION: Silent myocardial ischemia occurs in more than one in five asymptomatic diabetic patients. The strongest predictors of ischemia in this study were: patient age, peripheral neuropathy, nephropathy, retinopathy and a stress ECG positive for ischemia.OBJETIVO: Este estudo teve por finalidade avaliar a perfusão miocárdica de pacientes com diabetes mellitus tipo 1 (DM1) e tipo 2 (DM2) assintomáticos, sem diagnóstico prévio de doença arterial coronariana (DAC) ou acidente vascular cerebral. MATERIAIS E MÉTODOS: Cinquenta e nove pacientes consecutivos (16 DM1, 43 DM2) foram submetidos a cintilografia de perfusão miocárdica com sestamibi-99mTc (CPM). Foram avaliados quanto ao índice de massa corpórea, controle metabólico do diabetes, dislipidemia, terapia para o diabetes, hipertensão arterial sistêmica, nefropatia, retinopatia, neuropatia periférica, tabagismo e história familiar de DAC. RESULTADOS: CPM foi anormal em 25,4%: 12 (20,3%) com alterações de perfusão e 3 com disfunção ventricular esquerda isolada. Os mais fortes preditores de perfusão miocárdica anormal foram: idade igual ou maior a 60 anos (p = 0,017, odds ratio [OR] = 6,0), neuropatia periférica (p = 0,028, OR = 6,1), nefropatia (p = 0,031, OR = 5,6) e ECG de esforço positivo para isquemia (p = 0,049, OR = 4,08). CONCLUSÃO: A isquemia miocárdica silenciosa ocorre em mais de um em cada cinco diabéticos assintomáticos. Os mais fortes preditores de isquemia foram: idade avançada, neuropatia periférica, nefropatia, retinopatia e ECG de esforço positivo para isquemia.714Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Aplicación del modelo alternativo de diagnóstico de Trastorno de la Personalidad DSM-5 para valorar la evolución de una paciente adolescente: caso clínico

La quinta edición del Manual Diagnóstico y Estadístico de Trastornos Mentales, en su Sección III, presenta un modelo alternativo para el diagnóstico de los Trastornos de la Personalidad que intenta eliminar algunos de los problemas que aparecen con el modelo oficial presentado en la sección II del manual. Es de considerable interés la posibilidad que ofrece este modelo, cuyos ejes son el funcionamiento de la personalidad y los rasgos de la personalidad, de poder caracterizar con precisión a un paciente que cumple criterios de varios trastornos de la personalidad o no cumple criterios de uno concreto. También se contempla la posibilidad de utilizarlo como herramienta para la valoración de la funcionalidad de un paciente y el diseño de un plan terapéutico en función de su personalidad. En este artículo se presenta a una paciente con alteraciones del comportamiento, se caracteriza su personalidad según este modelo y se observa su evolución.The Diagnostic and Statistical Manual of Mental Disorders, fifth edition, presents in its Section III an alternative model for diagnosing Personality Disorders, which tries to amend some of the problems of the official model, included in Section II. Is it of remarkable interest the possibility that this model, whose main axes are the personality functioning and the personality traits, brings us of being able to characterize with precision a patient that meets criteria of more than one personality disorders or does not fully meet criteria for a single one. The possibility of using it as a tool to evaluate the functioning of a patient and designing a specific treatment plan according to his or her personality is also contemplated. In this article is present a patient whose behaviour is altered, her personality is characterised according to this model and he evolution is observed

Comparison of the activities of C2N and BCNO towards Congo red degradation

An n-type organic carbon nitride semiconductor, C2N, was synthesized by the pyrolysis of uric acid, and its properties were investigated by scanning electron and transmission electron microscopies, X-ray powder diffraction, and vibrational, UV-visible and X-ray photoelectron spectroscopies. This novel material, composed of crystalline flakes, featured a broad absorption centered at 700¿nm, possibly due to charge transfer, and a 2.49¿eV band gap. Its catalytic performance was assessed for the treatment of effluents with the diazo dye Congo red, comparing it with that of boron carbon nitrogen oxide, BCNO. Both wide band gap semiconductors exhibited decolorizing activity in the dark, although the mechanisms were different and were not photocatalytic: BCNO was more effective towards the adsorption-coordination due to the presence of B-O, while C2N was effective towards the adsorption and the advancement of the oxidation reaction. Their kinetic constants (0.19 and 0.02 min-1 for BCNO and C2N, respectively) were comparable to those of intermetallic compounds studied for azo dyes degradation in dark conditions. In view of the high color removal efficiency (97% after 20¿min) and good reusability of BCNO, this study suggests a potential application of this catalyst for wastewater treatment, alone or in combination with C2N

Strong relationships between soil and vegetation in reference ecosystems of a riparian atlantic rainforest in the upper Doce River watershed, southeastern Brazil

Habitat loss and fragmentation have been impacting ecosystem services essential for human survival. The Brazilian Atlantic rainforest, a biodiversity hotspot, has suffered from historical deforestation and, more recently, from an environmental disaster caused by the Fundão dam collapse that released ore tailings drastically affecting a large territory in the Doce River watershed. This work aims to assess the relationships between soil properties and vegetation in a reference ecosystem to provide guidelines for restoration projects in areas affected by the dam collapse. We conducted phytosociological (vegetation characteristic) and soil quality studies in three distinct natural sites and studied different vegetation strata to better understand plant species composition in reference sites along the impacted Doce River and their potential role in community structuring and functioning. We recorded 140 species, 78 in the tree stratum, and 90 in the sapling stratum. Furthermore, our results highlight the influence of soil on floristic composition in the Atlantic rainforest. Smallscale edaphic variation influenced species composition in both sapling and tree strata. We also identified species of the same genus with strong association with the extremes of the edaphic gradient. Therefore, we highlight that studies in various regions along the Doce River watershed are of utmost importance to evaluate the association between species and soils. The particularities of the species are crucial to the effectiveness of restoration processes since this plant-soil correlation should not be extrapolated even within the same genus. This knowledge is of strategic relevance to provide scientificbased guidance for restoring these environments, aiming at the recovery of biodiversity and ecosystem services.Fil: Ramos, Letícia. Universidade Federal de Minas Gerais; BrasilFil: Negreiros, Daniel. Universidade Federal de Minas Gerais; BrasilFil: Ferreira, Bárbara S. Silva. Universidade Federal de Minas Gerais; BrasilFil: Figueiredo, João Carlos Gomes. Universidade Estadual de Montes Claros; BrasilFil: Paiva, Dario C.. Florida International University; Estados UnidosFil: Oki, Yumi. Universidade Federal de Minas Gerais; BrasilFil: De Souza Justino, Wénita. Universidade Federal de Minas Gerais; BrasilFil: Dos Santos, Rubens Manoel. Universidade Federal de Lavras; BrasilFil: Aguilar, Ramiro. Universidade Federal de Minas Gerais; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Nunes, Yule Roberta Ferreira. Universidade Estadual de Montes Claros; BrasilFil: Fernandes, G Wilson. Universidade Federal de Minas Gerais; Brasi

Rehabilitation of gait after stroke: a review towards a top-down approach

This document provides a review of the techniques and therapies used in gait rehabilitation after stroke. It also examines the possible benefits of including assistive robotic devices and brain-computer interfaces in this field, according to a top-down approach, in which rehabilitation is driven by neural plasticity

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Differences in the carcinogenic evaluation of glyphosate between the International Agency for Research on Cancer (IARC) and the European Food Safety Authority (EFSA)

The International Agency for Research on Cancer (IARC) Monographs Programme identifies chemicals, drugs, mixtures, occupational exposures, lifestyles and personal habits, and physical and biological agents that cause cancer in humans and has evaluated about 1000 agents since 1971. Monographs are written by ad hoc Working Groups (WGs) of international scientific experts over a period of about 12 months ending in an eight-day meeting. The WG evaluates all of the publicly available scientific information on each substance and, through a transparent and rigorous process,1 decides on the degree to which the scientific evidence supports that substance's potential to cause or not cause cancer in humans. For Monograph 112,2 17 expert scientists evaluated the carcinogenic hazard for four insecticides and the herbicide glyphosate.3 The WG concluded that the data for glyphosate meet the criteria for classification as a probable human carcinogen. The European Food Safety Authority (EFSA) is the primary agency of the European Union for risk assessments regarding food safety. In October 2015, EFSA reported4 on their evaluation of the Renewal Assessment Report5 (RAR) for glyphosate that was prepared by the Rapporteur Member State, the German Federal Institute for Risk Assessment (BfR). EFSA concluded that ?glyphosate is unlikely to pose a carcinogenic hazard to humans and the evidence does not support classification with regard to its carcinogenic potential?. Addendum 1 (the BfR Addendum) of the RAR5 discusses the scientific rationale for differing from the IARC WG conclusion. Serious flaws in the scientific evaluation in the RAR incorrectly characterise the potential for a carcinogenic hazard from exposure to glyphosate. Since the RAR is the basis for the European Food Safety Agency (EFSA) conclusion,4 it is critical that these shortcomings are corrected

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease