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1.
Methods Mol Biol ; 2390: 103-112, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34731465

RESUMO

The development of vaccines for the treatment of COVID-19 is paving the way for new hope. Despite this, the risk of the virus mutating into a vaccine-resistant variant still persists. As a result, the demand of efficacious drugs to treat COVID-19 is still pertinent. To this end, scientists continue to identify and repurpose marketed drugs for this new disease. Many of these drugs are currently undergoing clinical trials and, so far, only one has been officially approved by FDA. Drug repurposing is a much faster route to the clinic than standard drug development of novel molecules, nevertheless in a pandemic this process is still not fast enough to halt the spread of the virus. Artificial intelligence has already played a large part in hastening the drug discovery process, not only by facilitating the selection of potential drug candidates but also in monitoring the pandemic and enabling faster diagnosis of patients. In this chapter, we focus on the impact and challenges that artificial intelligence has demonstrated thus far with respect to drug repurposing of therapeutics for the treatment of COVID-19.


Assuntos
Antivirais/uso terapêutico , Inteligência Artificial , COVID-19/tratamento farmacológico , Descoberta de Drogas , Reposicionamento de Medicamentos , SARS-CoV-2/efeitos dos fármacos , Animais , Antivirais/efeitos adversos , COVID-19/diagnóstico , COVID-19/virologia , Interações Hospedeiro-Patógeno , Humanos , Aprendizado de Máquina , Estrutura Molecular , SARS-CoV-2/patogenicidade , Relação Estrutura-Atividade
2.
Methods Mol Biol ; 2390: 177-190, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34731469

RESUMO

We describe an approach to early stage drug discovery that explicitly engages with the complexities of human biology. The combined computational and experimental approach is formulated on a conceptual framework in which network biology is used to bridge between individual molecular entities and the cellular phenotype that emerges when those entities interact in a network. Multiple aspects of early stage discovery are addressed including the data-driven elucidation of biological processes implicated in disease, target identification and validation, phenotypic discovery of active molecules and their mechanism of action, and extraction of genetic target support from human population genetics data. Validation is described via summary of a number of discovery projects and details from a project aimed at COVID-19 disease.


Assuntos
Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Descoberta de Drogas , SARS-CoV-2/efeitos dos fármacos , Biologia de Sistemas , Animais , Antivirais/efeitos adversos , COVID-19/diagnóstico , COVID-19/virologia , Interações Hospedeiro-Patógeno , Humanos , Estrutura Molecular , Terapia de Alvo Molecular , SARS-CoV-2/patogenicidade , Relação Estrutura-Atividade
3.
Gene ; 808: 145963, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34530086

RESUMO

As of July 2021, the outbreak of coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has led to more than 200 million infections and more than 4.2 million deaths globally. Complications of severe COVID-19 include acute kidney injury, liver dysfunction, cardiomyopathy, and coagulation dysfunction. Thus, there is an urgent need to identify proteins and genetic factors associated with COVID-19 susceptibility and outcome. We comprehensively reviewed recent findings of host-SARS-CoV-2 interactome analyses. To identify genetic variants associated with COVID-19, we focused on the findings from genome and transcriptome wide association studies (GWAS and TWAS) and bioinformatics analysis. We described established human proteins including ACE2, TMPRSS2, 40S ribosomal subunit, ApoA1, TOM70, HLA-A, and PALS1 interacting with SARS-CoV-2 based on cryo-electron microscopy results. Furthermore, we described approximately 1000 human proteins showing evidence of interaction with SARS-CoV-2 and highlighted host cellular processes such as innate immune pathways affected by infection. We summarized the evidence on more than 20 identified candidate genes in COVID-19 severity. Predicted deleterious and disruptive genetic variants with possible effects on COVID-19 infectivity have been also summarized. These findings provide novel insights into SARS-CoV-2 biology and infection as well as potential strategies for development of novel COVID therapeutic targets and drug repurposing.


Assuntos
COVID-19/metabolismo , Interações entre Hospedeiro e Microrganismos/genética , SARS-CoV-2/metabolismo , COVID-19/fisiopatologia , Biologia Computacional/métodos , Microscopia Crioeletrônica/métodos , Cristalografia por Raios X/métodos , Estudo de Associação Genômica Ampla , Interações entre Hospedeiro e Microrganismos/fisiologia , Interações Hospedeiro-Patógeno/genética , Humanos , Proteínas/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/patogenicidade
4.
Artigo em Inglês | MEDLINE | ID: mdl-34753828

RESUMO

BACKGROUND AND OBJECTIVES: There are limited data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine reactogenicity in persons with multiple sclerosis (PwMS) and how reactogenicity is affected by disease-modifying therapies (DMTs). The objective of this retrospective cross-sectional study was to generate real-world multiple sclerosis-specific vaccine safety information, particularly in the context of specific DMTs, and provide information to mitigate specific concerns in vaccine hesitant PwMS. METHODS: Between 3/2021 and 6/2021, participants in iConquerMS, an online people-powered research network, reported SARS-CoV-2 vaccines, experiences of local (itch, pain, redness, swelling, or warmth at injection site) and systemic (fever, chills, fatigue, headache, joint pain, malaise, muscle ache, nausea, allergic, and other) reactions within 24 hours (none, mild, moderate, and severe), DMT use, and other attributes. Multivariable models characterized associations between clinical factors and reactogenicity. RESULTS: In 719 PwMS, 64% reported experiencing a reaction after their first vaccination shot, and 17% reported a severe reaction. The most common reactions were pain at injection site (54%), fatigue (34%), headache (28%), and malaise (21%). Younger age, being female, prior SARS-CoV-2 infection, and receiving the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vs BNT162b2 (Pfizer-BioNTech) vaccine were associated with experiencing a reaction after the first vaccine dose. Similar relationships were observed for a severe reaction, including higher odds of reactions among PwMS with more physical impairment and lower odds of reactions for PwMS on an alpha4-integrin blocker or sphingosine-1-phosphate receptor modulator. In 442 PwMS who received their second vaccination shot, 74% reported experiencing a reaction, whereas 22% reported a severe reaction. Reaction profiles after the second shot were similar to those reported after the first shot. Younger PwMS and those who received the mRNA-1273 (Moderna) vs BNT162b2 vaccine reported higher reactogenicity after the second shot, whereas those on a sphingosine-1-phosphate receptor modulator or fumarate were significantly less likely to report a reaction. DISCUSSION: SARS-CoV-2 vaccine reactogenicity profiles and the associated factors in this convenience sample of PwMS appear similar to those reported in the general population. PwMS on specific DMTs were less likely to report vaccine reactions. Overall, the short-term vaccine reactions experienced in the study population were mostly self-limiting, including pain at the injection site, fatigue, headache, and fever.


Assuntos
Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , COVID-19/complicações , COVID-19/imunologia , Imunogenicidade da Vacina/imunologia , Esclerose Múltipla/complicações , Esclerose Múltipla/imunologia , Adulto , Idoso , COVID-19/prevenção & controle , COVID-19/virologia , Estudos Transversais , Feminino , Humanos , Imunização Secundária/efeitos adversos , Internet , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/virologia , Estudos Retrospectivos , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Inquéritos e Questionários , Vacinação/efeitos adversos , Vacinação/estatística & dados numéricos
5.
Gene ; 807: 145933, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34464678

RESUMO

BACKGROUND: Cervical-cancer is among the most commonly diagnosed cancers in women, and infection with human papillomavirus (HPV) is associated with an increased risk of cervical cancer and altered serum concentrations of inflammatory cytokines. We have explored the association between a genetic variation in the Interleukin-10 (IL-10) gene (rs1800896) and cervical cancer risk and its relationship with tissue Interferon gamma (IFN-γ), Transforming growth factor beta (TGF-ß), Tumor necrosis factor alpha (TNF-α) concentrations in women with cervical cancer. METHODS: A total of 315 women with, or without cervical cancer, were recruited into the study. DNA was extracted from cervical cells, and genotyping was undertaken using Taq-man real-time PCR. The genotype frequency and allele distribution were analyzed together with their association with pathological data. The association of the rs1800896 gene variation with tissue levels of the inflammatory cytokines was also investigated. RESULTS: Our data showed a significant association between the A allele of the rs1800896 gene variant and the presence of cervical cancer. In particular, patients with AG/AA genotypes had an increased risk of cervical cancer with an odds ratio of 1.929 (95% confidence interval [CI]: 0.879-4.23, P < 0.001) in a recessive model, compared with the GG genotype. Also, the tissue concentrations of IFN-γ, TGF-ß, and TNF-α in cervical tissues were significantly higher in women with cervical cancer (P < 0.001) and were associated with the AA genotype. CONCLUSION: We have found an association between the polymorphism rs1800896 in the IL-10 gene and an increased risk of cervical cancer as well as a higher level of tissue inflammatory cytokines. Further investigations are necessary on the value of emerging biomarkers for the risk stratification for the management of cervical cancer patients.


Assuntos
Interleucina-10/genética , Neoplasias do Colo do Útero/genética , Adulto , Alelos , Alphapapillomavirus/genética , Alphapapillomavirus/patogenicidade , Citocinas , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Inflamação , Interferon gama , Interleucina-10/metabolismo , Pessoa de Meia-Idade , Razão de Chances , Papillomaviridae/genética , Papillomaviridae/patogenicidade , Polimorfismo de Nucleotídeo Único/genética , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Risco , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
6.
J Med Virol ; 94(1): 7-10, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34506635

RESUMO

Hepatitis, a significant cause of mortality worldwide, results in around 1.34 million deaths each year globally. Africa is not exempt from the plague of Hepatitis. Around 100 million estimated individuals are infected with Hepatitis B or C. Egypt has the highest prevalence of cases of Hepatitis followed by Cameroon and Burundi. The continent is severely affected by the onset of the COVID-19 pandemic, as the virus has added an additional burden on the already fragile continent. With the pandemic, it is presumable that Hepatitis like other viral diseases will pose a threat to collapsing healthcare system. Therefore, for Africa to become more resilient in the face of such menaces, including Hepatitis, further prevention policies are required to be implemented.


Assuntos
COVID-19/epidemiologia , Acesso aos Serviços de Saúde , Hepatite B Crônica/epidemiologia , Hepatite C Crônica/epidemiologia , Países em Desenvolvimento , Egito/epidemiologia , Hepacivirus/patogenicidade , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/prevenção & controle , Hepatite B Crônica/terapia , Hepatite C Crônica/prevenção & controle , Hepatite C Crônica/terapia , Humanos , Fígado/lesões , Fígado/patologia , Fígado/virologia , Prevalência , SARS-CoV-2
7.
Infect Dis Poverty ; 10(1): 130, 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34742346

RESUMO

BACKGROUND: Cystic echinococcosis (CE), caused by the larval stage of the complex Echinococcus granulosus sensu lato (s.l.), is a zoonotic parasitic disease with a high social burden in China. E. ortleppi is a species (formerly genotype 5 of E. granulosus s.l.) with unique epidemic areas (tropical areas), transmission patterns (mainly cattle origin), and pathological characteristics (large and small hook lengths) compared to other species that cause CE. A 19-year-old female patient in an area with no history of echinococcosis in Guizhou Province, China, was diagnosed with E. ortleppi infection in 2019. This study is to understand the source of this human E. ortleppi infection. METHODS: We performed computer tomography (CT) scans, surgical operation, morphological sectioning, molecular diagnosis, phylogenetic analyses, and epidemiological investigation in Anshun City, Guizhou Province, China in 2019. RESULTS: The patient presented with intermittent distension and pain in the upper abdomen without other abnormal symptoms. Routine blood examination results were normal. However, abdominal CT revealed a fertile cyst with a diameter of approximately 8 cm, uniform density, and a clear boundary, but without an evident cyst wall in the right lobe of the liver. The cyst was fertile, and phylogenetic analyses revealed that the isolates represented a new E. ortleppi genus haplotype. A result of 10‒14 years incubation period with indigenous infection was considered available for the case through the epidemiological survey. CONCLUSIONS: CE due to E. ortleppi infection can be confused with other diseases causing liver cysts, resulting in misdiagnosis. A transmission chain of E. ortleppi may exist or existed in the past in the previously considered non-endemic areas of echinococcosis in southwestern China.


Assuntos
Equinococose , Echinococcus , Animais , China/epidemiologia , Equinococose/diagnóstico , Equinococose/epidemiologia , Echinococcus/genética , Echinococcus/patogenicidade , Feminino , Genótipo , Humanos , Filogenia , Adulto Jovem
9.
Front Immunol ; 12: 732913, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34737743

RESUMO

Obesity prevails worldwide to an increasing effect. For example, up to 42% of American adults are considered obese. Obese individuals are prone to a variety of complications of metabolic disorders including diabetes mellitus, hypertension, cardiovascular disease, and chronic kidney disease. Recent meta-analyses of clinical studies in patient cohorts in the ongoing coronavirus-disease 2019 (COVID-19) pandemic indicate that the presence of obesity and relevant disorders is linked to a more severe prognosis of COVID-19. Given the significance of obesity in COVID-19 progression, we provide a review of host metabolic and immune responses in the immunometabolic dysregulation exaggerated by obesity and the viral infection that develops into a severe course of COVID-19. Moreover, sequela studies of individuals 6 months after having COVID-19 show a higher risk of metabolic comorbidities including obesity, diabetes, and kidney disease. These collectively implicate an inter-systemic dimension to understanding the association between obesity and COVID-19 and suggest an interdisciplinary intervention for relief of obesity-COVID-19 complications beyond the phase of acute infection.


Assuntos
COVID-19/imunologia , COVID-19/metabolismo , Obesidade/imunologia , Obesidade/metabolismo , COVID-19/complicações , Progressão da Doença , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade , Doenças Metabólicas/imunologia , Doenças Metabólicas/metabolismo , Obesidade/complicações , Prognóstico , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença
10.
Braz J Biol ; 84: e253451, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34730701

RESUMO

Root-knot nematode Meloidogyne incognita is among the biotic factors which has greatly affected both the yield and the quality of the tomato crop. The egg parasitic nematode, Purpureocillium lilacinum (Pl) is considered as one of the most promising agents in controlling and overcoming this plant pathogen. The nematicidal effect of the native isolate Pl AUMC 10149 on second stage juvenile's survival and egg hatching of M. incognita at different times of exposure was tested in vitro. The obtained data showed that Pl gave a maximum percentage of J2 mortality (97.6%) and egg hatching inhibition (79.8%) after 72 hours of exposure. The potentiality of Pl as well as Bio-Nematon to control M. incognita infecting tomato was conducted using different times of application in vivo. Nine treatments with five replicates were used for such bioagents compared with the nematicide Oxamyl. Each seedling was inoculated with 1000 J2s of nematode/pot and 10 mL of Pl (1x1010 CFU/mL) or Bio-Nematon spore suspension (1x108 CFU/mL) 10mL/pot. The results indicated that the most effective treatments in reducing nematode population, number of galls and egg masses of M. incognita in plant roots was performed with treatment by Pl pre-planting and post-infection with Pl (Rf 1.9) giving a significant enhancement in plant length (64.9%), fresh weight (72.52%) and shoot dry weight (163.41%) without negatively impacting environment. Therefore, the present study confirmed that using P. lilacinum AUMC 10149 can be used as a practical supplement to environmentally friendly disease management of root-knot nematodes in Egypt.


Assuntos
Agentes de Controle Biológico , Hypocreales , Lycopersicon esculentum , Tylenchoidea , Animais , Lycopersicon esculentum/parasitologia , Tylenchoidea/patogenicidade
11.
Sci Rep ; 11(1): 21658, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34737323

RESUMO

More than one year since Coronavirus disease 2019 (COVID-19) pandemic outbreak, the gold standard technique for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection is still the RT-qPCR. This is a limitation to increase testing capacities, particularly at developing countries, as expensive reagents and equipment are required. We developed a two steps end point RT-PCR reaction with SARS-CoV-2 Nucleocapsid (N) gene and Ribonuclease P (RNase P) specific primers where viral amplicons were verified by agarose gel electrophoresis. We carried out a clinical performance and analytical sensitivity evaluation for this two-steps end point RT-PCR method with 242 nasopharyngeal samples using the CDC RT-qPCR protocol as a gold standard technique. With a specificity of 95.8%, a sensitivity of 95.1%, and a limit of detection of 20 viral RNA copies/uL, this two steps end point RT-PCR assay is an affordable and reliable method for SARS-CoV-2 detection. This protocol would allow to extend COVID-19 diagnosis to basic molecular biology laboratories with a potential positive impact in surveillance programs at developing countries.


Assuntos
Teste de Ácido Nucleico para COVID-19/métodos , COVID-19/diagnóstico , SARS-CoV-2/genética , COVID-19/genética , Teste de Ácido Nucleico para COVID-19/economia , Teste para COVID-19/métodos , Proteínas do Nucleocapsídeo de Coronavírus/genética , Primers do DNA , Eletroforese em Gel de Ágar/métodos , Humanos , Laboratórios , Nasofaringe/virologia , RNA Viral/genética , Ribonuclease P/genética , Ribonuclease P/metabolismo , SARS-CoV-2/patogenicidade , Sensibilidade e Especificidade
12.
Sci Rep ; 11(1): 21844, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34737319

RESUMO

This study assesses attitudes towards COVID-19 vaccination and the predictive value of COVID-VAC, a novel scale, among adults in the four largest US metropolitan areas and nationally. A 36-item survey of 6037 Americans was conducted in mid-April 2021. The study reports factors for COVID-19 vaccine acceptance among: (1) already vaccinated; (2) unvaccinated but willing to accept a vaccine; and (3) unvaccinated and unwilling to vaccinate. More than 20% were unwilling to vaccinate, expressing concerns about vaccine efficacy and safety and questioning the disease's severity. Poverty, working outside of the home and conservative political views are predictors of unwillingness. Conversely, those who either personally tested positive for COVID-19, or had a family member who did so, were more likely to accept vaccination. Majorities of all respondents supported vaccination mandates for employees and university students. Respondents preferred to receive vaccines in their doctor´s office. Lower income and conservative ideology, but not race, were strongly associated with vaccine unwillingness. The predictive value of COVID-VAC was demonstrated. While vaccination mandates are likely to be accepted, additional effective, targeted interventions to increase vaccine uptake are needed urgently.


Assuntos
COVID-19/psicologia , Recusa de Vacinação/psicologia , Recusa de Vacinação/tendências , Adulto , Atitude , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/provisão & distribuição , Feminino , Fidelidade a Diretrizes/tendências , Política de Saúde/tendências , Humanos , Intenção , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/patogenicidade , Inquéritos e Questionários , Estados Unidos , Vacinação/psicologia , Vacinação/tendências , Vacinas/farmacologia
13.
Sci Rep ; 11(1): 21654, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34737327

RESUMO

To slow the spread of infectious disease, it is crucial to understand the engagement of protective behavior among individuals. The purpose of this study was to systematically examine individuals' protective behaviors and the associated factors across countries during COVID-19. This causal-comparative study used a self-developed online survey to assess individuals' level of engagement with six protective behaviors. Analysis of variance and McNemar's test were employed for data analysis. Three hundred and eighty-four responses were analyzed. The majority of participants lived in three areas: Taiwan, Japan, and North America. Overall, the participants reported a high level of engagement in protective behaviors. However, engagement levels varied according to several demographic variables. Hand hygiene and cleaning/ventilation are two independent behaviors that differ from almost all other protective behaviors. There is a need to target the population at risk, which demonstrates low compliance. Different strategies are needed to promote specific protective behaviors.


Assuntos
COVID-19/prevenção & controle , COVID-19/psicologia , Comportamento de Redução do Risco , Adulto , Feminino , Higiene das Mãos/tendências , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Distanciamento Físico , SARS-CoV-2/patogenicidade , Inquéritos e Questionários
14.
Sci Rep ; 11(1): 21650, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34737362

RESUMO

The SARS-CoV2 has now spread worldwide causing over four million deaths. Testing strategies are highly variable between countries and their impact on mortality is a major issue. Retrospective multicenter study with a prospective database on all inpatients throughout mainland France. Using fixed effects models, we exploit policy discontinuities at region borders in France to estimate the effect of testing on the case fatality rate. In France, testing policies are determined at a regional level, generating exogenous variation in testing rates between departments on each side of a region border. We compared all contiguous department pairs located on the opposite sides of a region border. The increase of one percentage point in the test rate is associated with a decrease of 0.0015 percentage point in the death rate, that is, for each additional 2000 tests, we could observe three fewer deaths. Our study suggests that COVID-19 population testing could have a significant impact on the mortality rate which should be considered in decision-making. As concern grows over the current second wave of COVID-19, our findings support the implementation of large-scale screening strategies in such epidemic contexts.


Assuntos
Teste para COVID-19/tendências , COVID-19/diagnóstico , COVID-19/mortalidade , França/epidemiologia , Humanos , Programas de Rastreamento/métodos , Programas de Rastreamento/tendências , Mortalidade/tendências , Estudos Retrospectivos , SARS-CoV-2/patogenicidade
15.
Sci Rep ; 11(1): 21633, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34737330

RESUMO

Although the serum lipidome is markedly affected by COVID-19, two unresolved issues remain: how the severity of the disease affects the level and the composition of serum lipids and whether serum lipidome analysis may identify specific lipids impairment linked to the patients' outcome. Sera from 49 COVID-19 patients were analyzed by untargeted lipidomics. Patients were clustered according to: inflammation (C-reactive protein), hypoxia (Horowitz Index), coagulation state (D-dimer), kidney function (creatinine) and age. COVID-19 patients exhibited remarkable and distinctive dyslipidemia for each prognostic factor associated with reduced defense against oxidative stress. When patients were clustered by outcome (7 days), a peculiar lipidome signature was detected with an overall increase of 29 lipid species, including-among others-four ceramide and three sulfatide species, univocally related to this analysis. Considering the lipids that were affected by all the prognostic factors, we found one sphingomyelin related to inflammation and viral infection of the respiratory tract and two sphingomyelins, that are independently related to patients' age, and they appear as candidate biomarkers to monitor disease progression and severity. Although preliminary and needing validation, this report pioneers the translation of lipidome signatures to link the effects of five critical clinical prognostic factors with the patients' outcomes.


Assuntos
COVID-19/metabolismo , Lipídeos/sangue , Soro/química , Adulto , Idoso , Biomarcadores/sangue , COVID-19/sangue , Dislipidemias/metabolismo , Feminino , Humanos , Itália , Lipidômica/métodos , Lipídeos/análise , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Prognóstico , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidade , Esfingomielinas/sangue
16.
Sci Rep ; 11(1): 21700, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34737373

RESUMO

With recurring waves of the Covid-19 pandemic, a dilemma facing public health leadership is whether to provide public advice that is medically optimal (e.g., most protective against infection if followed), but unlikely to be adhered to, or advice that is less protective but is more likely to be followed. To provide insight about this dilemma, we examined and quantified public perceptions about the tradeoff between (a) the stand-alone value of health behavior advice, and (b) the advice's adherence likelihood. In a series of studies about preference for public health leadership advice, we asked 1061 participants to choose between (5) strict advice that is medically optimal if adhered to but which is less likely to be broadly followed, and (2) relaxed advice, which is less medically effective but more likely to gain adherence-given varying infection expectancies. Participants' preference was consistent with risk aversion. Offering an informed choice alternative that shifts volition to advice recipients only strengthened risk aversion, but also demonstrated that informed choice was preferred as much or more than the risk-averse strict advice.


Assuntos
COVID-19/psicologia , Fidelidade a Diretrizes/tendências , Disseminação de Informação/métodos , Adolescente , Adulto , Idoso , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Saúde Pública/tendências , Política Pública/tendências , Comportamento de Redução do Risco , SARS-CoV-2/patogenicidade
17.
Sci Rep ; 11(1): 21707, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34737382

RESUMO

We investigate the connection between the choice of transportation mode used by commuters and the probability of COVID-19 transmission. This interplay might influence the choice of transportation means for years to come. We present data on commuting, socioeconomic factors, and COVID-19 disease incidence for several US metropolitan areas. The data highlights important connections between population density and mobility, public transportation use, race, and increased likelihood of transmission. We use a transportation model to highlight the effect of uncertainty about transmission on the commuters' choice of transportation means. Using multiple estimation techniques, we found strong evidence that public transit ridership in several US metro areas has been considerably impacted by COVID-19 and by the policy responses to the pandemic. Concerns about disease transmission had a negative effect on ridership, which is over and above the adverse effect from the observed reduction in employment. The COVID-19 effect is likely to reduce the demand for public transport in favor of lower density alternatives. This change relative to the status quo will have implications for fuel use, congestion, accident frequency, and air quality. More vulnerable communities might be disproportionally affected as a result. We point to the need for additional studies to further quantify these effects and to assist policy in planning for the post-COVID-19 transportation future.


Assuntos
COVID-19/transmissão , Transportes/economia , Transportes/estatística & dados numéricos , Cidades , Emprego/tendências , Humanos , Veículos Automotores/economia , Veículos Automotores/estatística & dados numéricos , Pandemias , Densidade Demográfica , Dinâmica Populacional/tendências , SARS-CoV-2/patogenicidade , Fatores Socioeconômicos , Transportes/métodos , Estados Unidos/epidemiologia
18.
Sci Rep ; 11(1): 21675, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34737389

RESUMO

The recent outbreak of the COVID-19 led to death of millions of people worldwide. To stave off the spread of the virus, the authorities in the US employed different strategies, including the mask mandate order issued by the states' governors. In the current work, we defined a parameter called average death ratio as the monthly average of the number of daily deaths to the monthly average number of daily cases. We utilized survey data to quantify people's abidance by the mask mandate order. Additionally, we implicitly addressed the extent to which people abide by the mask mandate order, which may depend on some parameters such as population, income, and education level. Using different machine learning classification algorithms, we investigated how the decrease or increase in death ratio for the counties in the US West Coast correlates with the input parameters. The results showed that for the majority of counties, the mask mandate order decreased the death ratio, reflecting the effectiveness of such a preventive measure on the West Coast. Additionally, the changes in the death ratio demonstrated a noticeable correlation with the socio-economic condition of each county. Moreover, the results showed a promising classification accuracy score as high as 90%.


Assuntos
COVID-19/mortalidade , COVID-19/prevenção & controle , Máscaras/tendências , California , Fidelidade a Diretrizes/tendências , Política de Saúde , Humanos , Aprendizado de Máquina , Máscaras/estatística & dados numéricos , Oregon , SARS-CoV-2/patogenicidade , Washington
19.
Int J Mol Sci ; 22(21)2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34769038

RESUMO

Tetraspanins are transmembrane glycoproteins that have been shown increasing interest as host factors in infectious diseases. In particular, they were implicated in the pathogenesis of both non-enveloped (human papillomavirus (HPV)) and enveloped (human immunodeficiency virus (HIV), Zika, influenza A virus, (IAV), and coronavirus) viruses through multiple stages of infection, from the initial cell membrane attachment to the syncytium formation and viral particle release. However, the mechanisms by which different tetraspanins mediate their effects vary. This review aimed to compare and contrast the role of tetraspanins in the life cycles of HPV, HIV, Zika, IAV, and coronavirus viruses, which cause the most significant health and economic burdens to society. In doing so, a better understanding of the relative contribution of tetraspanins in virus infection will allow for a more targeted approach in the treatment of these diseases.


Assuntos
Interações Hospedeiro-Patógeno/fisiologia , Tetraspaninas/fisiologia , Viroses/metabolismo , Regulação Viral da Expressão Gênica , HIV-1/patogenicidade , Humanos , Vírus da Influenza A/patogenicidade , Papillomaviridae/patogenicidade , SARS-CoV-2/patogenicidade , Viroses/genética , Viroses/virologia , Internalização do Vírus , Zika virus/patogenicidade
20.
Int J Mol Sci ; 22(21)2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34769056

RESUMO

The angiotensin-converting enzyme 2 (ACE2) is the receptor used by SARS-CoV and SARS-CoV-2 coronaviruses to attach to cells via the receptor-binding domain (RBD) of their viral spike protein. Since the start of the COVID-19 pandemic, several structures of protein complexes involving ACE2 and RBD as well as monoclonal antibodies and nanobodies have become available. We have leveraged the structural data to design peptides to target the interaction between the RBD of SARS-CoV-2 and ACE2 and SARS-CoV and ACE2, as contrasting exemplar, as well as the dimerization surface of ACE2 monomers. The peptides were modelled using our original method: PiPreD that uses native elements of the interaction between the targeted protein and cognate partner(s) that are subsequently included in the designed peptides. These peptides recapitulate stretches of residues present in the native interface plus novel and highly diverse conformations surrogating key interactions at the interface. To facilitate the access to this information we have created a freely available and dedicated web-based repository, PepI-Covid19 database, providing convenient access to this wealth of information to the scientific community with the view of maximizing its potential impact in the development of novel therapeutic and diagnostic agents.


Assuntos
Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/metabolismo , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Peptídeos/farmacologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Sítios de Ligação , Bases de Dados Factuais , Humanos , Modelos Moleculares , Biblioteca de Peptídeos , Peptídeos/química , Conformação Proteica , Domínios Proteicos , Engenharia de Proteínas , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/química
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