15 research outputs found

    A Bioinformatics Approach to Investigate Structural and Non-Structural Proteins in Human Coronaviruses

    Get PDF
    Recent studies confirmed that people unexposed to SARS-CoV-2 have preexisting reactivity, probably due to previous exposure to widely circulating common cold coronaviruses. Such preexistent reactivity against SARS-CoV-2 comes from memory T cells that can specifically recognize a SARS-CoV-2 epitope of structural and non-structural proteins and the homologous epitopes from common cold coronaviruses. Therefore, it is important to understand the SARS-CoV-2 cross-reactivity by investigating these protein sequence similarities with those of different circulating coronaviruses. In addition, the emerging SARS-CoV-2 variants lead to an intense interest in whether mutations in proteins (especially in the spike) could potentially compromise vaccine effectiveness. Since it is not clear that the differences in clinical outcomes are caused by common cold coronaviruses, a deeper investigation on cross-reactive T-cell immunity to SARS-CoV-2 is crucial to examine the differential COVID-19 symptoms and vaccine performance. Therefore, the present study can be a starting point for further research on cross-reactive T cell recognition between circulating common cold coronaviruses and SARS-CoV-2, including the most recent variants Delta and Omicron. In the end, a deep learning approach, based on Siamese networks, is proposed to accurately and efficiently calculate a BLAST-like similarity score between protein sequences

    Urban air pollution, climate and its impact on asthma morbidity

    Get PDF
    AbstractObjectiveTo study the mechanism of formation of air quality and to determine the impact of the studied factors on asthma morbidity in Vladivostok.MethodsThe evaluation of air pollution in Vladivostok was done using long-term (2008–2012) monitoring data (temperature, humidity, atmospheric pressure, wind speed, etc.). The levels of suspended particulate matter, nitrogen and sulfur dioxide, carbon monoxide, ammonia, formaldehyde (mg/m3) in six stationary observation posts were assessed. We studied the aerosol suspensions of solid particles, which were collected during snowfall from precipitation (snow) and air in 14 districts with different levels of anthropogenic impact. Melted snow was analyzed on laser granulometry. The impact of air pollution on the distribution of asthma morbidity was evaluated in various age groups by data of federal statistical observation obtained from 8 adults and 7 children municipal clinics in Vladivostok (2008–2012).ResultsThe content of suspended particulate components of pollution remained more stable, due to the features of atmospheric circulation, rugged terrain and residential development. The nano- and micro-sized particles (0–50 μm), which can absorb highly toxic metals, prevail in dust aerosols. These respirable fractions of particles, even in small doses, can contribute to the increase in asthma morbidity in the city.ConclusionsWe determined that asthma morbidity depends from general air pollution (in the range of 18.3%). It was detected that the highest age-specific dependence is associated with the content of particulate matter, carbon monoxide and nitrogen dioxide in air

    Mortes evitáveis em vítimas com traumatismos

    Get PDF
    OBJETIVO: Descrever métodos e estimativas de mortalidade proporcional por mortes evitáveis e tipos de não conformidades do atendimento relacionadas a esses eventos. MÉTODOS: Revisão sistemática de publicações sobre mortes evitáveis em vítimas com traumatismos entre 2000 e 2009. Foi realizada pesquisa nas bases de dados Lilacs, SciELO e Medline utilizando-se a estratégia de busca com as palavras-chave "trauma", "avoidable", "preventable", "interventions" e "complications", e os descritores em ciências da saúde "death", "cause of death" e "hospitals". RESULTADOS: Identificaram-se 29 artigos publicados no período, com predomínio de estudos retrospectivos (96,5%). Os métodos mais comumente utilizados para definir a evitabilidade do óbito foram painel de especialistas ou pontuação de índices de gravidade, tendo sido empregadas as seguintes categorias: evitável, potencialmente evitável e não evitável. A média da mortalidade proporcional por mortes evitáveis dos estudos foi de 10,7% (dp 11,5%). As não conformidades mais comumente relatadas nas publicações foram sistema inadequado de atendimento ao traumatizado e erro na avaliação e tratamento. CONCLUSÕES: Observaram-se falhas na uniformização dos termos empregados para categorizar as mortes e as não conformidadades encontradas. Portanto, sugere-se a padronização da taxonomia da classificação das mortes e dos tipos de não conformidades observadas

    1-Aryl-3,5-dihydro-4H-2,3-benzodiazepin-4-ones: novel AMPA receptor antagonists.

    No full text
    Our previous publication (Eur. J. Pharmacol. 1995, 294, 411-422) reported preliminary chemical and biological studies of some 2,3-benzodiazepines, analogues of 1-(4-aminophenyl)-4-methyl-7,8-(methylenedioxy)-5H-2,3-benzodiazepine (1, GYKI 52466), which have been shown to possess significant anticonvulsant activity. This paper describes the synthesis of new 1-aryl-3,5-dihydro-4H-2,3-benzodiazepin-4-ones and the evaluation of their anticonvulsant effects. The observed findings extend the structure-activity relationships previously suggested for this class of anticonvulsants. The seizures were evoked both by means of auditory stimulation in DBA/2 mice and by pentylenetetrazole or maximal electroshock in Swiss mice. 1-(4'-Aminophenyl)- (38) and 1-(3'-aminophenyl)-3,5-dihydro-7,8-dimethoxy-4H-2,3-benzodiazepin- 4-one (39), the most active compounds of the series, proved to be more potent than 1 in all tests employed. In particular, the ED50 values against tonus evoked by auditory stimulation were 12.6 micromol/kg for derivative 38, 18.3 micromol/kg for 39, and 25.3 micromol/kg for 1. Higher doses were necessary to block tonic extension induced both by maximal electroshock and by pentylenetetrazole. In addition these compounds exhibited anticonvulsant properties that were longer lasting than those of compound 1 and were less toxic. The novel 2,3-benzodiazepines were also investigated for a possible correlation between their anticonvulsant activities against convulsions induced by 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) and their affinities for benzodiazepine receptors (BZR). The 2,3-benzodiazepines did not affect the binding of [3H]flumazenil to BZR, and conversely, their anticonvulsant effects were not reversed by flumazenil. On the other hand the 2,3-benzodiazepines antagonized seizures induced by AMPA and aniracetam in agreement with an involvement of the AMPA receptor. In addition, both the derivative 38 and the compound 1 markedly reduced the AMPA receptor-mediated membrane currents in guinea-pig olfactory cortical neurons in vitro in a noncompetitive manner. The derivatives 25 and 38-40 failed to displace specific ligands from N-methyl-D-aspartate (NMDA), AMPA/kainate, or metabotropic glutamate receptors
    corecore