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2.
Epidemiol Infect ; 148: e212, 2020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32873352

RESUMO

Corona virus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first detected in the city of Wuhan, China in December 2019. Although, the disease appeared in Africa later than other regions, it has now spread to virtually all countries on the continent. We provide early spatio-temporal dynamics of COVID-19 within the first 62 days of the disease's appearance on the African continent. We used a two-parameter hurdle Poisson model to simultaneously analyse the zero counts and the frequency of occurrence. We investigate the effects of important healthcare capacities including hospital beds and number of medical doctors in different countries. The results show that cases of the pandemic vary geographically across Africa with notably high incidence in neighbouring countries particularly in West and North Africa. The burden of the disease (per 100 000) mostly impacted Djibouti, Tunisia, Morocco and Algeria. Temporally, during the first 4 weeks, the burden was highest in Senegal, Egypt and Mauritania, but by mid-April it shifted to Somalia, Chad, Guinea, Tanzania, Gabon, Sudan and Zimbabwe. Currently, Namibia, Angola, South Sudan, Burundi and Uganda have the least burden. These findings could be useful in guiding epidemiological interventions and the allocation of scarce resources based on heterogeneity of the disease patterns.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , África/epidemiologia , Surtos de Doenças , Humanos , Pandemias , Distribuição de Poisson
3.
Spat Spatiotemporal Epidemiol ; 34: 100354, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32807396

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first discovered in late 2019 in Wuhan City, China. The virus may cause novel coronavirus disease 2019 (COVID-19) in symptomatic individuals. Since December of 2019, there have been over 7,000,000 confirmed cases and over 400,000 confirmed deaths worldwide. In the United States (U.S.), there have been over 2,000,000 confirmed cases and over 110,000 confirmed deaths. COVID-19 case data in the United States has been updated daily at the county level since the first case was reported in January of 2020. There currently lacks a study that showcases the novelty of daily COVID-19 surveillance using space-time cluster detection techniques. In this paper, we utilize a prospective Poisson space-time scan statistic to detect daily clusters of COVID-19 at the county level in the contiguous 48 U.S. and Washington D.C. As the pandemic progresses, we generally find an increase of smaller clusters of remarkably steady relative risk. Daily tracking of significant space-time clusters can facilitate decision-making and public health resource allocation by evaluating and visualizing the size, relative risk, and locations that are identified as COVID-19 hotspots.


Assuntos
Doenças Transmissíveis Emergentes/epidemiologia , Infecções por Coronavirus/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Pandemias/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Infecções por Coronavirus/diagnóstico , Bases de Dados Factuais , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Modelos Estatísticos , Método de Monte Carlo , Pneumonia Viral/diagnóstico , Distribuição de Poisson , Prevalência , Estudos Prospectivos , Saúde Pública , Síndrome Respiratória Aguda Grave/diagnóstico , Conglomerados Espaço-Temporais , Estados Unidos/epidemiologia
4.
PLoS One ; 15(8): e0237901, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817697

RESUMO

Among the different indicators that quantify the spread of an epidemic such as the on-going COVID-19, stands first the reproduction number which measures how many people can be contaminated by an infected person. In order to permit the monitoring of the evolution of this number, a new estimation procedure is proposed here, assuming a well-accepted model for current incidence data, based on past observations. The novelty of the proposed approach is twofold: 1) the estimation of the reproduction number is achieved by convex optimization within a proximal-based inverse problem formulation, with constraints aimed at promoting piecewise smoothness; 2) the approach is developed in a multivariate setting, allowing for the simultaneous handling of multiple time series attached to different geographical regions, together with a spatial (graph-based) regularization of their evolutions in time. The effectiveness of the approach is first supported by simulations, and two main applications to real COVID-19 data are then discussed. The first one refers to the comparative evolution of the reproduction number for a number of countries, while the second one focuses on French departments and their joint analysis, leading to dynamic maps revealing the temporal co-evolution of their reproduction numbers.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Modelos Estatísticos , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Análise Espaço-Temporal , Algoritmos , Infecções por Coronavirus/virologia , Bases de Dados Factuais , Transmissão de Doença Infecciosa/estatística & dados numéricos , França/epidemiologia , Humanos , Pandemias , Pneumonia Viral/virologia , Distribuição de Poisson , Software
5.
N Engl J Med ; 383(6): 537-545, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32757522

RESUMO

BACKGROUND: In 2015 and 2016, Colombia had a widespread outbreak of Zika virus. Data from two national population-based surveillance systems for symptomatic Zika virus disease (ZVD) and birth defects provided complementary information on the effect of the Zika virus outbreak on pregnancies and infant outcomes. METHODS: We collected national surveillance data regarding cases of pregnant women with ZVD that were reported during the period from June 2015 through July 2016. The presence of Zika virus RNA was identified in a subgroup of these women on real-time reverse-transcriptase-polymerase-chain-reaction (rRT-PCR) assay. Brain or eye defects in infants and fetuses and other adverse pregnancy outcomes were identified among the women who had laboratory-confirmed ZVD and for whom data were available regarding pregnancy outcomes. We compared the nationwide prevalence of brain and eye defects during the outbreak with the prevalence both before and after the outbreak period. RESULTS: Of 18,117 pregnant women with ZVD, the presence of Zika virus was confirmed in 5926 (33%) on rRT-PCR. Of the 5673 pregnancies with laboratory-confirmed ZVD for which outcomes had been reported, 93 infants or fetuses (2%) had brain or eye defects. The incidence of brain or eye defects was higher among pregnancies in which the mother had an onset of ZVD symptoms in the first trimester than in those with an onset during the second or third trimester (3% vs. 1%). A total of 172 of 5673 pregnancies (3%) resulted in pregnancy loss; after the exclusion of pregnancies affected by birth defects, 409 of 5426 (8%) resulted in preterm birth and 333 of 5426 (6%) in low birth weight. The prevalence of brain or eye defects during the outbreak was 13 per 10,000 live births, as compared with a prevalence of 8 per 10,000 live births before the outbreak and 11 per 10,000 live births after the outbreak. CONCLUSIONS: In pregnant women with laboratory-confirmed ZVD, brain or eye defects in infants or fetuses were more common during the Zika virus outbreak than during the periods immediately before and after the outbreak. The frequency of such defects was increased among women with a symptom onset early in pregnancy. (Funded by the Colombian Instituto Nacional de Salud and the Centers for Disease Control and Prevention.).


Assuntos
Encéfalo/anormalidades , Surtos de Doenças , Anormalidades do Olho/epidemiologia , Complicações Infecciosas na Gravidez , Infecção por Zika virus/complicações , Zika virus/isolamento & purificação , Adolescente , Adulto , Colômbia/epidemiologia , Feminino , Doenças Fetais/epidemiologia , Feto/anormalidades , Geografia Médica , Humanos , Incidência , Recém-Nascido , Masculino , Microcefalia/epidemiologia , Distribuição de Poisson , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Resultado da Gravidez , Prevalência , RNA Viral/sangue , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem , Zika virus/genética , Infecção por Zika virus/epidemiologia
6.
Exp Parasitol ; 217: 107962, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32763249

RESUMO

Trypanosoma cruzi is a parasitic protozoan that infects various species of domestic and wild animals, triatomine bugs and humans. It is the etiological agent of American trypanosomiasis, also known as Chagas Disease, which affects about 17 million people in Latin America and is emerging elsewhere in the world. Iron (Fe) is a crucial micronutrient for almost all cells, acting as a cofactor for several metabolic enzymes. T. cruzi has a high requirement for Fe, using heminic and non-heminic Fe for growth and differentiation. Fe occurs in the oxidized (Fe3+) form in aerobic environments and needs to be reduced to Fe2+ before it enters cells. Fe-reductase, located in the plasma membranes of some organisms, catalyzes the Fe3+⇒ Fe2+ conversion. In the present study we found an amino acid sequence in silico that allowed us to identify a novel 35 kDa protein in T. cruzi with two transmembrane domains in the C-terminal region containing His residues that are conserved in the Ferric Reductase Domain Superfamily and are required for catalyzing Fe3+ reduction. Accordingly, we named this protein TcFR. Intact epimastigotes from the T. cruzi DM28c strain reduced the artificial Fe3+-containing substrate potassium ferricyanide in a cell density-dependent manner, following Michaelis-Menten kinetics. The TcFR activity was more than eightfold higher in a plasma membrane-enriched fraction than in whole homogenates, and this increase was consistent with the intensity of the 35 kDa band on Western blotting images obtained using anti-NOX5 raised against the human antigen. Immunofluorescence experiments demonstrated TcFR on the parasite surface. That TcFR is part of a catalytic complex allowing T. cruzi to take up Fe from the medium was confirmed by experiments in which DM28c was assayed after culturing in Fe-depleted medium: (i) proliferation during the stationary growth phase was five times slower; (ii) the relative expression of TcFR (qPCR) was 50% greater; (iii) intact cells had 120% higher Fe-reductase activity. This ensemble of results indicates that TcFR is a conserved enzyme in T. cruzi, and its catalytic properties are modulated in order to respond to external Fe fluctuations.


Assuntos
FMN Redutase/metabolismo , Ferro/metabolismo , Trypanosoma cruzi/enzimologia , Sequência de Aminoácidos , Animais , Western Blotting , Membrana Celular/enzimologia , Doença de Chagas/parasitologia , Colorimetria , FMN Redutase/análise , FMN Redutase/química , Imunofluorescência , Humanos , Filogenia , Distribuição de Poisson , Reação em Cadeia da Polimerase em Tempo Real , Alinhamento de Sequência , Trypanosoma cruzi/classificação , Trypanosoma cruzi/crescimento & desenvolvimento , Trypanosoma cruzi/metabolismo , Regulação para Cima
7.
N Engl J Med ; 383(5): 415-425, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32726528

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants, and a need exists for prevention of RSV in healthy infants. Nirsevimab is a monoclonal antibody with an extended half-life that is being developed to protect infants for an entire RSV season with a single intramuscular dose. METHODS: In this trial conducted in both northern and southern hemispheres, we evaluated nirsevimab for the prevention of RSV-associated lower respiratory tract infection in healthy infants who had been born preterm (29 weeks 0 days to 34 weeks 6 days of gestation). We randomly assigned the infants in a 2:1 ratio to receive nirsevimab, at a dose of 50 mg in a single intramuscular injection, or placebo at the start of an RSV season. The primary end point was medically attended RSV-associated lower respiratory tract infection through 150 days after administration of the dose. The secondary efficacy end point was hospitalization for RSV-associated lower respiratory tract infection through 150 days after administration of the dose. RESULTS: From November 2016 through November 2017, a total of 1453 infants were randomly assigned to receive nirsevimab (969 infants) or placebo (484 infants) at the start of the RSV season. The incidence of medically attended RSV-associated lower respiratory tract infection was 70.1% lower (95% confidence interval [CI], 52.3 to 81.2) with nirsevimab prophylaxis than with placebo (2.6% [25 infants] vs. 9.5% [46 infants]; P<0.001) and the incidence of hospitalization for RSV-associated lower respiratory tract infection was 78.4% lower (95% CI, 51.9 to 90.3) with nirsevimab than with placebo (0.8% [8 infants] vs. 4.1% [20 infants]; P<0.001). These differences were consistent throughout the 150-day period after the dose was administered and across geographic locations and RSV subtypes. Adverse events were similar in the two trial groups, with no notable hypersensitivity reactions. CONCLUSIONS: A single injection of nirsevimab resulted in fewer medically attended RSV-associated lower respiratory tract infections and hospitalizations than placebo throughout the RSV season in healthy preterm infants. (Funded by AstraZeneca and Sanofi Pasteur; ClinicalTrials.gov number, NCT02878330.).


Assuntos
Anticorpos Monoclonais/administração & dosagem , Antivirais/administração & dosagem , Recém-Nascido Prematuro , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vírus Sincicial Respiratório Humano , Infecções Respiratórias/prevenção & controle , Proteínas Virais de Fusão/antagonistas & inibidores , Anticorpos Monoclonais/efeitos adversos , Antivirais/efeitos adversos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Lactente , Recém-Nascido , Injeções Intramusculares , Estimativa de Kaplan-Meier , Masculino , Distribuição de Poisson , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia
8.
N Engl J Med ; 383(5): 426-439, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32726529

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) is the dominant cause of severe lower respiratory tract infection in infants, with the most severe cases concentrated among younger infants. METHODS: Healthy pregnant women, at 28 weeks 0 days through 36 weeks 0 days of gestation, with an expected delivery date near the start of the RSV season, were randomly assigned in an overall ratio of approximately 2:1 to receive a single intramuscular dose of RSV fusion (F) protein nanoparticle vaccine or placebo. Infants were followed for 180 days to assess outcomes related to lower respiratory tract infection and for 364 days to assess safety. The primary end point was RSV-associated, medically significant lower respiratory tract infection up to 90 days of life, and the primary analysis of vaccine efficacy against the primary end point was performed in the per-protocol population of infants (prespecified criterion for success, lower bound of the 97.52% confidence interval [CI] of ≥30%). RESULTS: A total of 4636 women underwent randomization, and there were 4579 live births. During the first 90 days of life, the percentage of infants with RSV-associated, medically significant lower respiratory tract infection was 1.5% in the vaccine group and 2.4% in the placebo group (vaccine efficacy, 39.4%; 97.52% CI, -1.0 to 63.7; 95% CI, 5.3 to 61.2). The corresponding percentages for RSV-associated lower respiratory tract infection with severe hypoxemia were 0.5% and 1.0% (vaccine efficacy, 48.3%; 95% CI, -8.2 to 75.3), and the percentages for hospitalization for RSV-associated lower respiratory tract infection were 2.1% and 3.7% (vaccine efficacy, 44.4%; 95% CI, 19.6 to 61.5). Local injection-site reactions among the women were more common with vaccine than with placebo (40.7% vs. 9.9%), but the percentages of participants who had other adverse events were similar in the two groups. CONCLUSIONS: RSV F protein nanoparticle vaccination in pregnant women did not meet the prespecified success criterion for efficacy against RSV-associated, medically significant lower respiratory tract infection in infants up to 90 days of life. The suggestion of a possible benefit with respect to other end-point events involving RSV-associated respiratory disease in infants warrants further study. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov NCT02624947.).


Assuntos
Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vírus Sincicial Respiratório Humano , Infecções Respiratórias/prevenção & controle , Adolescente , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Hipóxia/etiologia , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Doenças do Recém-Nascido/prevenção & controle , Injeções Intramusculares , Nanopartículas , Distribuição de Poisson , Gravidez , Terceiro Trimestre da Gravidez , Infecções por Vírus Respiratório Sincicial/complicações , Infecções por Vírus Respiratório Sincicial/epidemiologia , Vírus Sincicial Respiratório Humano/imunologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Vacinação , Proteínas Virais de Fusão/imunologia , Adulto Jovem
9.
Euro Surveill ; 25(28)2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32700669

RESUMO

England has experienced one of the highest excess in all-cause mortality in Europe during the current COVID-19 pandemic. As COVID-19 emerged, the excess in all-cause mortality rapidly increased, starting in March 2020. The excess observed during the pandemic was higher than excesses noted in the past 5 years. It concerned all regions and all age groups, except the 0-14 year olds, but was more pronounced in the London region and in those aged ≥ 85 years.


Assuntos
Betacoronavirus , Infecções por Coronavirus/mortalidade , Pneumonia Viral/mortalidade , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Causas de Morte , Inglaterra/epidemiologia , Humanos , Pessoa de Meia-Idade , Pandemias , Distribuição de Poisson , Adulto Jovem
10.
Public Health ; 185: 266-269, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32707468

RESUMO

OBJECTIVES: Socio-economic inequalities may affect coronavirus disease 2019 (COVID-19) incidence. The goal of the research was to explore the association between deprivation of socio-economic status (SES) and spatial patterns of COVID-19 incidence in Chennai megacity for unfolding the disease epidemiology. STUDY DESIGN: This is an ecological (or contextual) study for electoral wards (subcities) of Chennai megacity. METHODS: Using data of confirmed COVID-19 cases from May 15, 2020, to May 21, 2020, for 155 electoral wards obtained from the official website of the Chennai Municipal Corporation, we examined the incidence of COVID-19 using two count regression models, namely, Poisson regression (PR) and negative binomial regression (NBR). As explanatory factors, we considered area deprivation that represented the deprivation of SES. An index of multiple deprivations (IMD) was developed to measure the area deprivation using an advanced local statistic, geographically weighted principal component analysis. Based on the availability of appropriately scaled data, five domains (i.e., poor housing condition, low asset possession, poor availability of WaSH services, lack of household amenities and services, and gender disparity) were selected as components of the IMD in this study. RESULTS: The hot spot analysis revealed that area deprivation was significantly associated with higher incidences of COVID-19 in Chennai megacity. The high variations (adjusted R2: 72.2%) with the lower Bayesian Information Criteria (BIC) (124.34) and Akaike's Information Criteria (AIC) (112.12) for NBR compared with PR suggests that the NBR model better explains the relationship between area deprivation and COVID-19 incidences in Chennai megacity. NBR with two-sided tests and P <0.05 were considered statistically significant. The outcome of the PR and NBR models suggests that when all other variables were constant, according to NBR, the relative risk (RR) of COVID-19 incidences was 2.19 for the wards with high housing deprivation or, in other words, the wards with high housing deprivation having 119% higher probability (RR = e0.786 = 2.19, 95% confidence interval [CI] = 1.98 to 2.40), compared with areas with low deprivation. Similarly, in the wards with poor availability of WaSH services, chances of having COVID-19 incidence was 90% higher than in the wards with good WaSH services (RR = e0.642 = 1.90, 95% CI = 1.79 to 2.00). Spatial risks of COVID-19 were predominantly concentrated in the wards with higher levels of area deprivation, which were mostly located in the northeastern parts of Chennai megacity. CONCLUSIONS: We formulated an area-based IMD, which was substantially related to COVID-19 incidences in Chennai megacity. This study highlights that the risks of COVID-19 tend to be higher in areas with low SES and that the northeastern part of Chennai megacity is predominantly high-risk areas. Our results can guide measures of COVID-19 control and prevention by considering spatial risks and area deprivation.


Assuntos
Infecções por Coronavirus/epidemiologia , Disparidades nos Níveis de Saúde , Pneumonia Viral/epidemiologia , Áreas de Pobreza , Distribuição Binomial , Cidades/epidemiologia , Feminino , Humanos , Incidência , Índia/epidemiologia , Masculino , Modelos Estatísticos , Pandemias , Distribuição de Poisson , Medição de Risco
11.
PLoS Comput Biol ; 16(7): e1007972, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32658891

RESUMO

Although quantitative insights into the killing behaviour of Cytotoxic T Lymphocytes (CTLs) are necessary for the rational design of immune-based therapies, CTL killing function remains insufficiently characterised. One established model of CTL killing treats CTL cytotoxicity as a Poisson process, based on the assumption that CTLs serially kill antigen-presenting target cells via delivery of lethal hits, each lethal hit corresponding to a single injection of cytotoxic proteins into the target cell cytoplasm. Contradicting this model, a recent in vitro study of individual CTLs killing targets over a 12-hour period found significantly greater heterogeneity in CTL killing performance than predicted by Poisson-based killing. The observed killing process was dynamic and varied between CTLs, with the best performing CTLs exhibiting a marked increase in killing during the final hours of the experiments, along with a "burst killing" kinetic. Despite a search for potential differences between CTLs, no mechanistic explanation for the heterogeneous killing kinetics was found. Here we have used stochastic simulations to assess whether target cells might require multiple hits from CTLs before undergoing apoptosis, in order to verify whether multiple-hitting could explain the late onset, burst killing dynamics observed in vitro. We found that multiple-hitting from CTLs was entirely consistent with the observed killing kinetics. Moreover, the number of available targets and the spatiotemporal kinetics of CTL:target interactions influenced the realised CTL killing rate. We subsequently used realistic, spatial simulations to assess methods for estimating the hitting rate and the number of hits required for target death, to be applied to microscopy data of individual CTLs killing targets. We found that measuring the cumulative duration of individual contacts that targets have with CTLs would substantially improve accuracy when estimating the killing kinetics of CTLs.


Assuntos
Citoplasma/metabolismo , Processos Estocásticos , Linfócitos T Citotóxicos/citologia , Linfócitos T Citotóxicos/imunologia , Actinas/química , Algoritmos , Células Apresentadoras de Antígenos , Apoptose , Movimento Celular , Simulação por Computador , Citotoxicidade Imunológica , Humanos , Cinética , Funções Verossimilhança , Método de Monte Carlo , Distribuição de Poisson
12.
PLoS Comput Biol ; 16(7): e1008012, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32658894

RESUMO

Single-cell DNA sequencing technologies are enabling the study of mutations and their evolutionary trajectories in cancer. Somatic copy number aberrations (CNAs) have been implicated in the development and progression of various types of cancer. A wide array of methods for CNA detection has been either developed specifically for or adapted to single-cell DNA sequencing data. Understanding the strengths and limitations that are unique to each of these methods is very important for obtaining accurate copy number profiles from single-cell DNA sequencing data. We benchmarked three widely used methods-Ginkgo, HMMcopy, and CopyNumber-on simulated as well as real datasets. To facilitate this, we developed a novel simulator of single-cell genome evolution in the presence of CNAs. Furthermore, to assess performance on empirical data where the ground truth is unknown, we introduce a phylogeny-based measure for identifying potentially erroneous inferences. While single-cell DNA sequencing is very promising for elucidating and understanding CNAs, our findings show that even the best existing method does not exceed 80% accuracy. New methods that significantly improve upon the accuracy of these three methods are needed. Furthermore, with the large datasets being generated, the methods must be computationally efficient.


Assuntos
Variações do Número de Cópias de DNA , Genoma Humano , Análise de Sequência de DNA/métodos , Análise de Célula Única/métodos , Algoritmos , Aberrações Cromossômicas , Biologia Computacional , Simulação por Computador , Dosagem de Genes , Humanos , Mutação , Neoplasias/genética , Ploidias , Distribuição de Poisson , Curva ROC , Reprodutibilidade dos Testes , Software
13.
PLoS Comput Biol ; 16(7): e1008069, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32716940

RESUMO

Nitric oxide (NO) is a gaseous signaling molecule that plays an important role in neurovascular coupling. NO produced by neurons diffuses into the smooth muscle surrounding cerebral arterioles, driving vasodilation. However, the rate of NO degradation in hemoglobin is orders of magnitude higher than in brain tissue, though how this might impact NO signaling dynamics is not completely understood. We used simulations to investigate how the spatial and temporal patterns of NO generation and degradation impacted dilation of a penetrating arteriole in cortex. We found that the spatial location of NO production and the size of the vessel both played an important role in determining its responsiveness to NO. The much higher rate of NO degradation and scavenging of NO in the blood relative to the tissue drove emergent vascular dynamics. Large vasodilation events could be followed by post-stimulus constrictions driven by the increased degradation of NO by the blood, and vasomotion-like 0.1-0.3 Hz oscillations could also be generated. We found that these dynamics could be enhanced by elevation of free hemoglobin in the plasma, which occurs in diseases such as malaria and sickle cell anemia, or following blood transfusions. Finally, we show that changes in blood flow during hypoxia or hyperoxia could be explained by altered NO degradation in the parenchyma. Our simulations suggest that many common vascular dynamics may be emergent phenomena generated by NO degradation by the blood or parenchyma.


Assuntos
Encéfalo/fisiologia , Circulação Cerebrovascular , Óxido Nítrico/metabolismo , Anemia Falciforme/fisiopatologia , Arteríolas , Transfusão de Sangue , Sistema Livre de Células , Simulação por Computador , Difusão , Células Endoteliais/metabolismo , Eritrócitos/metabolismo , Hemodinâmica , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Malária/fisiopatologia , Mitocôndrias/metabolismo , Músculo Liso/metabolismo , Oscilometria , Distribuição de Poisson , Transdução de Sinais , Vasodilatação
14.
BMC Infect Dis ; 20(1): 401, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503461

RESUMO

BACKGROUND: Visceral leishmaniasis is an important but neglected disease that is spreading and is highly lethal when left untreated. This study sought to measure the Leishmania infantum seroprevalence in dogs, the coverage of its control activities (identification of the canine reservoir by serological survey, dog culling and insecticide spraying) and to evaluate its relationship with the occurrence of the disease in humans in the municipalities of Araçatuba and Birigui, state of São Paulo, Brazil. METHODS: Information from 2006 to 2015 was georeferenced for each municipality and modeling was performed for the two municipalities together. To do this, latent Gaussian Bayesian models with the incorporation of a spatio-temporal structure and Poisson distribution were used. The Besag-York-Mollie models were applied for random spatial effects, as also were autoregressive models of order 1 for random temporal effects. The modeling was performed using the INLA (Integrated Nested Laplace Approximations) deterministic approach, considering both the numbers of cases as well as the coverage paired year by year and lagged at one and two years. RESULTS: Control activity coverage was observed to be generally low. The behavior of the temporal tendency in the human disease presented distinct patterns in the two municipalities, however, in both the tendency was to decline. The canine serological survey presented as a protective factor only in the two-year lag model. CONCLUSIONS: The canine serological coverage, even at low intensity, carried out jointly with the culling of the positive dogs, suggested a decreasing effect on the occurrence of the disease in humans, whose effects would be seen two years after it was carried out.


Assuntos
Formigas/parasitologia , Doenças do Cão/diagnóstico , Doenças do Cão/patologia , Leishmaniose Visceral/patologia , Animais , Teorema de Bayes , Brasil/epidemiologia , Doenças do Cão/epidemiologia , Cães , Humanos , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/epidemiologia , Distribuição de Poisson , Fatores de Risco , Estudos Soroepidemiológicos
15.
Rev Saude Publica ; 54: 56, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32556022

RESUMO

OBJECTIVE: To evaluate the incidence and persistence of fear of falling in older adults and the clinical/functional, psychosocial and lifestyle-related risk factors. METHODS: A longitudinal study with 393 community-dwelling older adults aged 65 years and over (110 men/ 283 women) resident in the North Zone of the city of Rio de Janeiro, Brazil. The fear of falling was assessed by the Falls Efficacy Scale-I-BR. The explanatory variables assessed were: number of comorbidities and medicines, history of falls, fracture from falling, use of walking aids, functional dependence in basic and instrumental activities of daily living, hearing and visual impairment, hand grip strength, walking speed, self-rated health, body mass index, depressive symptoms, cognitive impairment, living alone and activity level. Incidence, persistence and risk factors were estimated. Multivariate analysis was performed using Poisson Regression, obtaining relative risks (RR) and corresponding to 95% confidence intervals. RESULTS: Among the 393 participants, fear of falling occurred in 33.5% and was persistent in 71.3%. Incidence was found to associate with using seven or more medicines and reporting worse activity level than the prior year. Risk factors for persistent fear were: using seven or more medicines, a history of one or two falls, reduced walking speed, hearing impairment, cognitive impairment, depressive symptoms and poor or very poor self-rated health. CONCLUSION: Fear of falling is a frequent and persistent condition. Many factors related to persistent fear showed no association with the incidence of fear, emphasizing the need for focused strategies to reduce risk factors that may be associated with the chronification of fear of falling.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Avaliação Geriátrica/estatística & dados numéricos , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Medo , Feminino , Idoso Fragilizado/estatística & dados numéricos , Humanos , Incidência , Estilo de Vida , Estudos Longitudinais , Masculino , Distribuição de Poisson , Medição de Risco , Fatores de Risco , Fatores Socioeconômicos , Fatores de Tempo
16.
Epidemiol Infect ; 148: e123, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32580809

RESUMO

This study aims to identify the risk factors associated with mortality and survival of COVID-19 cases in a state of the Brazilian Northeast. It is a historical cohort with a secondary database of 2070 people that presented flu-like symptoms, sought health assistance in the state and tested positive to COVID-19 until 14 April 2020, only moderate and severe cases were hospitalised. The main outcome was death as a binary variable (yes/no). It also investigated the main factors related to mortality and survival of the disease. Time since the beginning of symptoms until death/end of the survey (14 April 2020) was the time variable of this study. Mortality was analysed by robust Poisson regression, and survival by Kaplan-Meier and Cox regression. From the 2070 people that tested positive to COVID-19, 131 (6.3%) died and 1939 (93.7%) survived, the overall survival probability was 87.7% from the 24th day of infection. Mortality was enhanced by the variables: elderly (HR 3.6; 95% CI 2.3-5.8; P < 0.001), neurological diseases (HR 3.9; 95% CI 1.9-7.8; P < 0.001), pneumopathies (HR 2.6; 95% CI 1.4-4.7; P < 0.001) and cardiovascular diseases (HR 8.9; 95% CI 5.4-14.5; P < 0.001). In conclusion, mortality by COVID-19 in Ceará is similar to countries with a large number of cases of the disease, although deaths occur later. Elderly people and comorbidities presented a greater risk of death.


Assuntos
Infecções por Coronavirus/mortalidade , Pneumonia Viral/mortalidade , Adulto , Fatores Etários , Idoso , Brasil/epidemiologia , Doenças Cardiovasculares/complicações , Estudos de Coortes , Comorbidade , Infecções por Coronavirus/complicações , Complicações do Diabetes/complicações , Feminino , Hospitalização , Humanos , Unidades de Terapia Intensiva , Estimativa de Kaplan-Meier , Nefropatias/complicações , Pneumopatias/complicações , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/complicações , Pandemias , Pneumonia Viral/complicações , Distribuição de Poisson , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores Sexuais , Fatores de Tempo
17.
Obesity (Silver Spring) ; 28(10): 1802-1805, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32589788

RESUMO

OBJECTIVE: This study aimed to examine the impact of the coronavirus disease (COVID-19) pandemic on patronage to unhealthy eating establishments in populations with obesity. METHODS: Anonymized movement data accounting for roughly 10% of devices in the United States at 138,989 unhealthy eating locations from December 1, 2019, through April 2020 and the percentage of adults with obesity, the poverty rate, and the food environment index in 65% of United States counties were collected and merged. A cluster corrected Poisson spline regression was performed predicting patronage by day, the percentage of adults with obesity in the establishment's county, the county's poverty rate, and its food environment index, as well as their interactions. RESULTS: Patronage to unhealthy eating establishments was higher where there was a higher percentage of the adult population with obesity. A similar pattern was observed for counties with a lower food environment index. These disparities appear to have increased as the COVID-19 pandemic spread. CONCLUSIONS: These results suggest unhealthy eating patterns during the COVID-19 pandemic are higher in already at-risk populations. Policy makers can use these findings to motivate interventions and programs aimed at increasing healthy food intake in at-risk communities during crises.


Assuntos
Infecções por Coronavirus/psicologia , Dieta Saudável/estatística & dados numéricos , Comportamento Alimentar/psicologia , Obesidade/psicologia , Pneumonia Viral/psicologia , Quarentena/estatística & dados numéricos , Adolescente , Adulto , Betacoronavirus , Análise por Conglomerados , Infecções por Coronavirus/prevenção & controle , Dieta Saudável/psicologia , Feminino , Abastecimento de Alimentos/estatística & dados numéricos , Humanos , Masculino , Obesidade/epidemiologia , Obesidade/virologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Distribuição de Poisson , Pobreza/psicologia , Pobreza/estatística & dados numéricos , Quarentena/psicologia , Análise de Regressão , Estados Unidos/epidemiologia , Adulto Jovem
18.
J Med Microbiol ; 69(8): 1124-1131, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32597749

RESUMO

Introduction. Acute otitis media (AOM) is the most common bacterial infection in early childhood, but the underlying mechanisms making some children more susceptible are poorly understood.Aim. To examine the associations between bacterial airway colonization in early life and the risk of AOM and tympanostomy tube insertion (TTI), and whether such associations are modulated by an insufficient local immune mediator response to bacterial colonization.Methodology. Bacterial cultures from hypopharyngeal samples were obtained at 1 week, 1 month and 3 months of age in the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) cohort comprising 700 children. Twenty immune mediators were quantified from airway mucosal lining fluid sampled at 1 month. AOM symptoms were registered in a daily diary until 3 years. Information on TTI in the first 3 years was obtained from national registers.Results. Children colonized with Streptococcus pneumoniae at 1 month of age had increased incidence of AOM [aIRR 2.43 (1.14-5.21)] and children colonized with Moraxella catarrhalis at 1 month or Haemophilus influenzae at 3 months had an increased risk of TTI [aHR 1.45 (1.00-2.10) and 1.73 (1.10-2.71)]. There were no associations between the local immune mediator response to colonization and risk of AOM or TTI.Conclusion. Pathogenic bacterial airway colonization in early life was found to be associated with an increased risk of otitis media, albeit not consistently. These associations were independent of the local immune response to colonization.


Assuntos
Otite Média/epidemiologia , Sistema Respiratório/imunologia , Sistema Respiratório/microbiologia , Análise de Variância , Distribuição de Qui-Quadrado , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Modelos Lineares , Otite Média/imunologia , Otite Média/microbiologia , Distribuição de Poisson , Análise de Componente Principal , Modelos de Riscos Proporcionais , Fatores de Risco , Estatísticas não Paramétricas
19.
BMC Infect Dis ; 20(1): 369, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: covidwho-343360

RESUMO

BACKGROUND: Previous studies have proven that the closure of live poultry markets (LPMs) was an effective intervention to reduce human risk of avian influenza A (H7N9) infection, but evidence is limited on the impact of scale and duration of LPMs closure on the transmission of H7N9. METHOD: Five cities (i.e., Shanghai, Suzhou, Shenzhen, Guangzhou and Hangzhou) with the largest number of H7N9 cases in mainland China from 2013 to 2017 were selected in this study. Data on laboratory-confirmed H7N9 human cases in those five cities were obtained from the Chinese National Influenza Centre. The detailed information of LPMs closure (i.e., area and duration) was obtained from the Ministry of Agriculture. We used a generalized linear model with a Poisson link to estimate the effect of LPMs closure, reported as relative risk reduction (RRR). We used classification and regression trees (CARTs) model to select and quantify the dominant factor of H7N9 infection. RESULTS: All five cities implemented the LPMs closure, and the risk of H7N9 infection decreased significantly after LPMs closure with RRR ranging from 0.80 to 0.93. Respectively, a long-term LPMs closure for 10-13 weeks elicited a sustained and highly significant risk reduction of H7N9 infection (RRR = 0.98). Short-time LPMs closure with 2 weeks in every epidemic did not reduce the risk of H7N9 infection (p > 0.05). Partially closed LPMs in some suburbs contributed only 35% for reduction rate (RRR = 0.35). Shenzhen implemented partial closure for first 3 epidemics (p > 0.05) and all closure in the latest 2 epidemic waves (RRR = 0.64). CONCLUSION: Our findings suggest that LPMs all closure in whole city can be a highly effective measure comparing with partial closure (i.e. only urban closure, suburb and rural remain open). Extend the duration of closure and consider permanently closing the LPMs will help improve the control effect. The effect of LPMs closure seems greater than that of meteorology on H7N9 transmission.


Assuntos
Epidemias/prevenção & controle , Subtipo H7N9 do Vírus da Influenza A , Influenza Aviária/epidemiologia , Influenza Aviária/transmissão , Influenza Humana/epidemiologia , Aves Domésticas/virologia , Animais , China/epidemiologia , Cidades/epidemiologia , Humanos , Umidade , Incidência , Influenza Aviária/virologia , Influenza Humana/virologia , Modelos Lineares , Distribuição de Poisson , Fatores de Risco , Temperatura , População Urbana
20.
Int J Infect Dis ; 95: 301-303, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: covidwho-170615

RESUMO

OBJECTIVES: To evaluate the influence of temperature on the infectivity of COVID-19 in Japan. METHODS: We evaluated the relationship between the accumulated number of patients per 1,000,000 population and the average temperature in February 2020 in each prefecture by Poisson regression analysis. We introduced the monthly number of inbound visitors from China in January 2020 in each prefecture and old-age dependency ratio as additional explanatory variables in the model. RESULTS: Monthly inbound visitors from China in January 2020, old-age dependency ratio, and mean temperature in February 2020 are associated with the cumulative number of COVID-19 case on March 16, 2020. CONCLUSIONS: Our analysis showed a possible association between low temperature and increased risk of COVID-19 infection. Further evaluation would be desirable at a global level.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , China/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Masculino , Pandemias , Distribuição de Poisson , Temperatura
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