In-hospital outcomes of Infective Endocarditis from 1978 to 2015: analysis through machine-learning techniques

© 2021 The Authors. Published by Elsevier Inc. on behalf of the Canadian Cardiovascular Society. This is an open access article under the CC BY-NC- ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Background: Early identification of patients with infective endocarditis (IE) at higher risk for in-hospital mortality is essential to guide management and improve prognosis. Methods: A retrospective analysis was conducted of a cohort of patients followed up from 1978 to 2015, classified according to the modified Duke criteria. Clinical parameters, echocardiographic data, and blood cultures were assessed. Techniques of machine learning, such as the classification tree, were used to explain the association between clinical characteristics and in-hospital mortality. Additionally, the log-linear model and graphical random forests (GRaFo) representation were used to assess the degree of dependence among in-hospital outcomes of IE. Results: This study analyzed 653 patients: 449 (69.0%) with definite IE; 204 (31.0%) with possible IE; mean age, 41.3 ± 19.2 years; 420 (64%) men. Mode of IE acquisition: community-acquired (67.6%), nosocomial (17.0%), undetermined (15.4%). Complications occurred in 547 patients (83.7%), the most frequent being heart failure (47.0%), neurologic complications (30.7%), and dialysis-dependent renal failure (6.5%). In-hospital mortality was 36.0%. The classification tree analysis identified subgroups with higher in-hospital mortality: patients with community-acquired IE and peripheral stigmata on admission; and patients with nosocomial IE. The log-linear model showed that surgical treatment was related to higher in-hospital mortality in patients with neurologic complications. Conclusions: The use of a machine-learning model allowed identification of subgroups of patients at higher risk for in-hospital mortality. Peripheral stigmata, nosocomial IE, absence of vegetation, and surgery in the presence of neurologic complications are predictors of fatal outcomes in machine learning-based analysis.info:eu-repo/semantics/publishedVersio

miRNA-31 Improves Cognition and Abolishes Amyloid-beta Pathology by Targeting APP and BACE1 in an Animal Model of Alzheimer's Disease

Alzheimer's disease (AD) is the most common form of dementia worldwide, characterized by progressive memory impairment, behavioral changes, and, ultimately, loss of consciousness and death. Recently, microRNA (miRNA) dysfunction has been associated with increased production and impaired clearance of amyloid-β (Aβ) peptides, whose accumulation is one of the most well-known pathophysiological markers of this disease. In this study, we identified several miRNAs capable of targeting key proteins of the amyloidogenic pathway. The expression of one of these miRNAs, miR-31, previously found to be decreased in AD patients, was able to simultaneously reduce the levels of APP and Bace1 mRNA in the hippocampus of 17-month-old AD triple-transgenic (3xTg-AD) female mice, leading to a significant improvement of memory deficits and a reduction in anxiety and cognitive inflexibility. In addition, lentiviral-mediated miR-31 expression significantly ameliorated AD neuropathology in this model, drastically reducing Aβ deposition in both the hippocampus and subiculum. Furthermore, the increase of miR-31 levels was enough to reduce the accumulation of glutamate vesicles in the hippocampus to levels found in non-transgenic age-matched animals. Overall, our results suggest that miR-31-mediated modulation of APP and BACE1 can become a therapeutic option in the treatment of AD.This work was financed by the European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme under the project CENTRO-01-0145-FEDER-000008: BrainHealth 2020 and through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT - Fundação para a Ciência e a Tecnologia, under the project POCI- 01-0145-FEDER-007440 (reference UID/NEU/04539/2013). This work was also supported by the FCT Investigator Programme (IF/ 00694/2013 to J.P.), the Marie Curie Carrier Integration Grant (PCIG13-GA-2013-618525 to J.P.), HEALTHYAGING 2020 (CENTRO-01-0145-FEDER-000012 to A.T.B.-V.), and Bial Foundation Grant 264/16. A.T.B.-V., J.G., and A.L.C. are recipients of fellowships from the FCT (Grants PTDC/BIM-MEC/0651/2012, SFRH/ BPD/120611/2016, and SFRH/BPD/108312/2015)

Identificação de Problemas e Propostas para Melhoria

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Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Neurotoxic effect of oligomeric and fibrillar species of A<beta>1-42 peptide. Involvement of ER calcium release in oligomers-induced cell death.

http://www.sciencedirect.com/science/article/B6T0F-4SSY90W-1/1/0b10903f573d4beaec42f0dc791857e

Modulation of adenosine in the persistence of Candida albicans inside macrophages

CAROÇO, Márcia Catarina Resende de Oliveira - Modulation of adenosine in the persistence of Candida albicans inside macrophages. Coimbra : [s.n.], 2016. Dissertação de Mestrado.With the development in today's society, the emergence of new, more drastic methods for treating diseases such as cancer, that weaken the immune system, leaving it more susceptible to opportunistic infections. C. albicans is a good example of a microorganism which takes advantage of the compromised immune system. As a commensal it is harmless and can be found in the microbiota of almost every human. However, changes in the host organism stimulate the passage of the fungus to opportunistic pathogen. Many factors influence the survival of this organism even in unfavorable environments for the same. Escape mechanisms of the host immune system is one of C. albicans strategies to avoid elimination. The modulation of the inflammatory response in the host appears as one of the possible ways that C. albicans survive within macrophages. Adenosine plays an important role in inflammation. It binds to the receptors at the cell membrane, such as the A2A receptor (A2AR) promoting the development of antiinflammatory responses, important for tissue protection when a deleterious inflammatory process occurs. Before, the research group described that in response to yeast infection A2AR at the cell membrane moves to the phagosomal membrane, inside the cell. According to this, the main objective of this study was to determine to what extent dipyridamole, an inhibitor of nucleoside transporters, influences the development of infection in the presence of adenosine, with the goal of emphasizing the presence of A2AR inside the cell. The most important conclusion to be drawn from this work is the reduction of C. albicans viability within macrophages in the presence of adenosine and dipyridamole. In this same condition, a decreased viability of macrophages indicates that the macrophage is more activated and efficient in the clearance of yeasts. Moreover, the profile of expression of the genes coding for IL-1β and TNF-α production in the presence of adenosine and dipyridamole also enhance the results obtained previously. This work can thus help the understanding of how C. albicans persists silently inside macrophages and to create new avenues of studying other strategies to effectively eliminate infections by this fungus.Com o desenvolvimento na sociedade atual, o aparecimento de novas metodologias mais drásticas para o tratamento de doenças, como o cancro, debilita o sistema imunitário, deixando-o mais suscetível a infeções oportunistas. C. albicans é um bom exemplo de um microrganismo que se aproveita do sistema imunitário comprometido. Como comensal é inofensivo, estando presente na microbiota de quase todos os humanos. No entanto, alterações no organismo do hospedeiro estimulam a passagem deste fungo a agente patogénico oportunista. Muitos fatores influenciam a sobrevivência deste microrganismo mesmo em ambientes desfavoráveis. Mecanismos de fuga ao sistema imunitário do hospedeiro é uma das estratégias de C. albicans para fugir à eliminação. A modulação da resposta inflamatória no hospedeiro surge como uma das possíveis vias pelas quais C. albicans sobrevive no interior de macrófagos. A adenosina desempenha um importante papel na inflamação. A sua ligação a recetores da membrana citoplasmática, como os recetores A2A (A2AR) promove o desenvolvimento da resposta anti-inflamatória, importante para a proteção de tecidos quando ocorre uma resposta inflamatória exacerbada. Antes, o grupo de investigação descreveu que no decurso de uma infeção por C. albicans os recetores A2AR encontram-se na membrana do fagossoma que encerra células de levedura. O principal objetivo deste trabalho foi verificar em que medida o dipiridamole, um inibidor dos transportadores de nucleósidos, influencia o desenvolvimento da infeção na presença de adenosina, com a finalidade de enfatizar a importância da localização intracelular dos A2AR. A conclusão mais importante deste trabalho é a diminuição do número de C. albicans no interior dos macrófagos na presença de adenosina e de dipiridamole. Por outro lado, ocorre uma diminuição da viabilidade dos macrófagos nas mesmas condições o que pode constituir um indício de que os macrófagos estão mais ativados e são mais eficientes na eliminação. Por outro lado, o perfil de expressão dos genes que codificam para IL-1β e TNF-α, na presença de adenosina e dipiridamole reforça os resultados previamente obtidos. Este trabalho poderá assim ajudar à compreensão deste mecanismo de proteção da C. albicans e futuramente ajudar à criação de novas vias estratégias para a eliminação eficaz deste fungo