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1.
Clin Infect Dis ; 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34864935

RESUMO

BACKGROUND: Residents of nursing homes (NH) are at high risk of COVID-19 related morbidity and death and may respond poorly to vaccination because of old age and frequent comorbidities. METHODS: Seventy-eight residents and 106 staff members, naïve or previously infected with SARS-CoV-2, were recruited in NH in Belgium before immunization with two doses of 30µg BNT162b2 mRNA vaccine at day 0 and day 21. Binding antibodies (Ab) to SARS-CoV-2 receptor binding domain (RBD), spike domains S1 and S2, RBD Ab avidity, and neutralizing Ab against SARS-CoV-2 wild type and B.1.351 were assessed at days 0, 21, 28, and 49. RESULTS: SARS-CoV-2 naïve residents had lower Ab responses to BNT162b2 mRNA vaccination than naïve staff. These poor responses involved lower levels of IgG to all spike domains, lower avidity of RBD IgG, and lower levels of Ab neutralizing the vaccine strain. No naïve resident had detectable neutralizing Ab to the B.1.351 variant. In contrast, SARS-CoV-2 infected residents had high responses to mRNA vaccination, with Ab levels comparable to infected staff. Cluster analysis revealed that poor vaccine responders not only included naïve residents but also naïve staff, emphasizing the heterogeneity of responses to mRNA vaccination in the general population. CONCLUSIONS: The poor Ab responses to mRNA vaccination observed in infection naïve residents and in some naïve staff members of NH suggest suboptimal protection against breakthrough infection, especially with variants of concern. These data support the administration of a third dose of mRNA vaccine to further improve protection of NH residents against COVID-19.

2.
Arch Public Health ; 79(1): 195, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34763723

RESUMO

BACKGROUND: The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented itself as one of the most important health concerns of the 2020's, and hit the geriatric population the hardest. The presence of co-morbidities and immune ageing in the elderly lead to an increased susceptibility to COVID-19, as is the case for other influenza-like illnesses (ILI) or acute respiratory tract infections (ARI). However, little is known, about the impact of a previous or current infection on the other in terms of susceptibility, immune response, and clinical course. The aim of the "Prior Infection with SARS-COV-2" (PICOV) study is to compare the time to occurrence of an ILI or ARI between participants with a confirmed past SARS-CoV-2 infection (previously infected) and those without a confirmed past infection (naïve) in residents and staff members of nursing homes. This paper describes the study design and population characteristics at baseline. METHODS: In 26 Belgian nursing homes, all eligible residents and staff members were invited to participate, resulting in 1,226 participants. They were classified as naïve or previously infected based on the presence of detectable SARS-CoV-2 antibodies and/or a positive RT-qPCR result before participation in the study. Symptoms from a prior SARS-CoV-2 infection between March and August 2020 were compared between previously infected residents and staff members. RESULTS: Infection naïve nursing home residents reported fewer symptoms than previously infected residents: on average 1.9 and 3.1 symptoms, respectively (p = 0.016). The same effect was observed for infection naïve staff members and previously infected staff members (3.1 and 6.1 symptoms, respectively; p <0.0001). Moreover, the antibody development after a SARS-CoV-2 infection differs between residents and staff members, as previously infected residents tend to have a higher rate of asymptomatic cases compared to previously infected staff members (20.5% compared to 12.4%; p <0.0001). CONCLUSIONS: We can postulate that COVID-19 disease development and symptomatology are different between a geriatric and younger population. Therefore, the occurrence and severity of a future ILI and/or ARI might vary from resident to staff.

3.
Euro Surveill ; 26(38)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34558405

RESUMO

BackgroundSeasonal influenza-like illness (ILI) affects millions of people yearly. Severe acute respiratory infections (SARI), mainly influenza, are a leading cause of hospitalisation and mortality. Increasing evidence indicates that non-influenza respiratory viruses (NIRV) also contribute to the burden of SARI. In Belgium, SARI surveillance by a network of sentinel hospitals has been ongoing since 2011.AimWe report the results of using in-house multiplex qPCR for the detection of a flexible panel of viruses in respiratory ILI and SARI samples and the estimated incidence rates of SARI associated with each virus.MethodsWe defined ILI as an illness with onset of fever and cough or dyspnoea. SARI was defined as an illness requiring hospitalisation with onset of fever and cough or dyspnoea within the previous 10 days. Samples were collected in four winter seasons and tested by multiplex qPCR for influenza virus and NIRV. Using catchment population estimates, we calculated incidence rates of SARI associated with each virus.ResultsOne third of the SARI cases were positive for NIRV, reaching 49.4% among children younger than 15 years. In children younger than 5 years, incidence rates of NIRV-associated SARI were twice that of influenza (103.5 vs 57.6/100,000 person-months); co-infections with several NIRV, respiratory syncytial viruses, human metapneumoviruses and picornaviruses contributed most (33.1, 13.6, 15.8 and 18.2/100,000 person-months, respectively).ConclusionEarly testing for NIRV could be beneficial to clinical management of SARI patients, especially in children younger than 5 years, for whom the burden of NIRV-associated disease exceeds that of influenza.


Assuntos
Influenza Humana , Orthomyxoviridae , Infecções Respiratórias , Vírus , Bélgica/epidemiologia , Criança , Humanos , Lactente , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Saúde Pública , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia , Vigilância de Evento Sentinela , Vírus/genética
4.
Microb Genom ; 7(9)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34477544

RESUMO

Seasonal influenza epidemics are associated with high mortality and morbidity in the human population. Influenza surveillance is critical for providing information to national influenza programmes and for making vaccine composition predictions. Vaccination prevents viral infections, but rapid influenza evolution results in emerging mutants that differ antigenically from vaccine strains. Current influenza surveillance relies on Sanger sequencing of the haemagglutinin (HA) gene. Its classification according to World Health Organization (WHO) and European Centre for Disease Prevention and Control (ECDC) guidelines is based on combining certain genotypic amino acid mutations and phylogenetic analysis. Next-generation sequencing technologies enable a shift to whole-genome sequencing (WGS) for influenza surveillance, but this requires laboratory workflow adaptations and advanced bioinformatics workflows. In this study, 253 influenza A(H3N2) positive clinical specimens from the 2016-2017 Belgian season underwent WGS using the Illumina MiSeq system. HA-based classification according to WHO/ECDC guidelines did not allow classification of all samples. A new approach, considering the whole genome, was investigated based on using powerful phylogenomic tools including beast and Nextstrain, which substantially improved phylogenetic classification. Moreover, Bayesian inference via beast facilitated reassortment detection by both manual inspection and computational methods, detecting intra-subtype reassortants at an estimated rate of 15 %. Real-time analysis (i.e. as an outbreak is ongoing) via Nextstrain allowed positioning of the Belgian isolates into the globally circulating context. Finally, integration of patient data with phylogenetic groups and reassortment status allowed detection of several associations that would have been missed when solely considering HA, such as hospitalized patients being more likely to be infected with A(H3N2) reassortants, and the possibility to link several phylogenetic groups to disease severity indicators could be relevant for epidemiological monitoring. Our study demonstrates that WGS offers multiple advantages for influenza monitoring in (inter)national influenza surveillance, and proposes an improved methodology. This allows leveraging all information contained in influenza genomes, and allows for more accurate genetic characterization and reassortment detection.

6.
BMC Infect Dis ; 21(1): 785, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376182

RESUMO

BACKGROUND: The severity of an influenza infection is influenced by both host and viral characteristics. This study aims to assess the relevance of viral genomic data for the prediction of severe influenza A(H3N2) infections among patients hospitalized for severe acute respiratory infection (SARI), in view of risk assessment and patient management. METHODS: 160 A(H3N2) influenza positive samples from the 2016-2017 season originating from the Belgian SARI surveillance were selected for whole genome sequencing. Predictor variables for severity were selected using a penalized elastic net logistic regression model from a combined host and genomic dataset, including patient information and nucleotide mutations identified in the viral genome. The goodness-of-fit of the model combining host and genomic data was compared using a likelihood-ratio test with the model including host data only. Internal validation of model discrimination was conducted by calculating the optimism-adjusted area under the Receiver Operating Characteristic curve (AUC) for both models. RESULTS: The model including viral mutations in addition to the host characteristics had an improved fit ([Formula: see text]=12.03, df = 3, p = 0.007). The optimism-adjusted AUC increased from 0.671 to 0.732. CONCLUSIONS: Adding genomic data (selected season-specific mutations in the viral genome) to the model containing host characteristics improved the prediction of severe influenza infection among hospitalized SARI patients, thereby offering the potential for translation into a prospective strategy to perform early season risk assessment or to guide individual patient management.


Assuntos
Influenza Humana , Genoma Viral , Genômica , Humanos , Vírus da Influenza A Subtipo H3N2/genética , Influenza Humana/diagnóstico , Estudos Prospectivos
7.
Eur J Med Chem ; 225: 113748, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34392191

RESUMO

Mechanical allodynia, a painful sensation caused by innocuous touch, is a major chronic pain symptom, which often remains without an effective treatment. There is thus a need for new anti-allodynic treatments based on new drug classes. We recently synthetized new 3,5-disubstituted pyridin-2(1H)-one derivatives. By substituting the pyridinone at the 3-position by various aryl/heteroaryl moieties and at the 5-position by a phenylamino group, we discovered that some derivatives exhibited a strong anti-allodynic potency in rats. Here, we report that varying the substitution of the pyridinone 5-position, the 3-position being substituted by an indol-4-yl moiety, further improves such anti-allodynic potency. Compared with 2, one of the two most active compounds of the first series, eleven out of nineteen newly synthetized compounds showed higher anti-allodynic potency, with two of them completely preventing mechanical allodynia. In the first series, hit compounds 1 and 2 appeared to be inhibitors of p38α MAPK, a protein kinase known to underlie pain hypersensitivity in animal models. Depending on the substitution at the 5-position, some newly synthetized compounds were also stronger p38α MAPK inhibitors. Surprisingly, though, anti-allodynic effects and p38α MAPK inhibitory potencies were not correlated, suggesting that other biological target(s) is/are involved in the analgesic activity in this series. Altogether, these results confirm that 3,5-disubstituted pyridine-2(1H)-one derivatives are of high interest for the development of new treatment of mechanical allodynia.

8.
BMJ Open ; 11(6): e050824, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187832

RESUMO

OBJECTIVES: To describe prevalence and incidence of anti-SARS-CoV-2 antibodies among Belgian hospital healthcare workers (HCW) in April-December 2020. DESIGN: Prospective cohort study. Follow-up was originally planned until September and later extended. SETTING: Multicentre study, 17 hospitals. PARTICIPANTS: 50 HCW were randomly selected per hospital. HCW employed beyond the end of the study and whose profession involved contact with patients were eligible. 850 HCW entered the study in April-May 2020, 673 HCW (79%) attended the September visit and 308 (36%) the December visit. OUTCOME MEASURES: A semiquantitative ELISA was used to detect IgG against SARS-CoV-2 in serum (Euroimmun) at 10 time points. In seropositive samples, neutralising antibodies were measured using a virus neutralisation test. Real-time reverse transcription PCR (RT-qPCR) was performed to detect SARS-CoV-2 on nasopharyngeal swabs. Participant characteristics and the presence of symptoms were collected via an online questionnaire. RESULTS: Among all participants, 80% were women, 60% nurses and 21% physicians. Median age was 40 years. The seroprevalence remained relatively stable from April (7.7% (95% CI: 4.8% to 12.1%) to September (8.2% (95% CI: 5.7% to 11.6%)) and increased thereafter, reaching 19.7% (95% CI: 12.0% to 30.6%) in December 2020. 76 of 778 initially seronegative participants seroconverted during the follow-up (incidence: 205/1000 person-years). Among all seropositive individuals, 118/148 (80%) had a positive neutralisation test, 83/147 (56%) presented or reported a positive RT-qPCR, and 130/147 (88%) reported COVID-19-compatible symptoms at least once. However, only 46/73 (63%) of the seroconverters presented COVID-19-compatible symptoms in the month prior to seroconversion. CONCLUSIONS: The seroprevalence among hospital HCW was slightly higher than that of the general Belgian population but followed a similar evolution, suggesting that infection prevention and control measures were effective and should be strictly maintained. After two SARS-CoV-2 waves, 80% of HCW remained seronegative, justifying their prioritisation in the vaccination strategy. TRIAL REGISTRATION NUMBER: NCT04373889.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Bélgica/epidemiologia , Feminino , Pessoal de Saúde , Hospitais , Humanos , Incidência , Prevalência , Estudos Prospectivos , Estudos Soroepidemiológicos , Vacinação
9.
Lancet Microbe ; 2(3): e105-e114, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33937883

RESUMO

Background: Seasonal human coronaviruses (hCoVs) broadly circulate in humans. Their epidemiology and effect on the spread of emerging coronaviruses has been neglected thus far. We aimed to elucidate the epidemiology and burden of disease of seasonal hCoVs OC43, NL63, and 229E in patients in primary care and hospitals in Belgium between 2015 and 2020. Methods: We retrospectively analysed data from the national influenza surveillance networks in Belgium during the winter seasons of 2015-20. Respiratory specimens were collected through the severe acute respiratory infection (SARI) and the influenza-like illness networks from patients with acute respiratory illness with onset within the previous 10 days, with measured or reported fever of 38°C or greater, cough, or dyspnoea; and for patients admitted to hospital for at least one night. Potential risk factors were recorded and patients who were admitted to hospital were followed up for the occurrence of complications or death for the length of their hospital stay. All samples were analysed by multiplex quantitative RT-PCRs for respiratory viruses, including seasonal hCoVs OC43, NL63, and 229E. We estimated the prevalence and incidence of seasonal hCoV infection, with or without co-infection with other respiratory viruses. We evaluated the association between co-infections and potential risk factors with complications or death in patients admitted to hospital with seasonal hCoV infections by age group. Samples received from week 8, 2020, were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Findings: 2573 primary care and 6494 hospital samples were included in the study. 161 (6·3%) of 2573 patients in primary care and 371 (5·7%) of 6494 patients admitted to hospital were infected with a seasonal hCoV. OC43 was the seasonal hCoV with the highest prevalence across age groups and highest incidence in children admitted to hospital who were younger than 5 years (incidence 9·0 [95% CI 7·2-11·2] per 100 000 person-months) and adults older than 65 years (2·6 [2·1-3·2] per 100 000 person-months). Among 262 patients admitted to hospital with seasonal hCoV infection and with complete information on potential risk factors, 66 (73·3%) of 90 patients who had complications or died also had at least one potential risk factor (p=0·0064). Complications in children younger than 5 years were associated with co-infection (24 [36·4%] of 66; p=0·017), and in teenagers and adults (≥15 years), more complications arose in patients with a single hCoV infection (49 [45·0%] of 109; p=0·0097). In early 2020, the Belgian SARI surveillance detected the first SARS-CoV-2-positive sample concomitantly with the first confirmed COVID-19 case with no travel history to China. Interpretation: The main burden of severe seasonal hCoV infection lies with children younger than 5 years with co-infections and adults aged 65 years and older with pre-existing comorbidities. These age and patient groups should be targeted for enhanced observation when in medical care and in possible future vaccination strategies, and co-infections in children younger than 5 years should be considered during diagnosis and treatment. Our findings support the use of national influenza surveillance systems for seasonal hCoV monitoring and early detection, and monitoring of emerging coronaviruses such as SARS-CoV-2. Funding: Belgian Federal Public Service Health, Food Chain Safety, and Environment; Belgian National Insurance Health Care (Institut national d'assurance maladie-invalidité/Rijksinstituut voor ziekte-en invaliditeitsverzekering); and Regional Health Authorities (Flanders Agentschap zorg en gezondheid, Brussels Commission communautaire commune, Wallonia Agence pour une vie de qualité).

10.
J Med Virol ; 93(10): 5783-5788, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34050945

RESUMO

More and more rapid antigen tests for the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appear in the market with varying performance. The sensitivity of these tests heavily depends on the viral load, extrapolated by the threshold cycle (Ct). It is therefore essential to verify their performance before their inclusion in routine. The Coronavirus Ag Rapid Test Cassette Bio-Rad, the GSD NovaGen SARS-CoV-2 (COVID-19) Antigen Rapid Test, and the Aegle Coronavirus Ag Rapid Test Cassette were evaluated on 199 samples: 150 fresh samples from the routine and positive in quantitative reverse-transcription polymerase chain reaction (RT-qPCR), nine fresh samples negative in RT-qPCR, and 40 frozen samples, taken before the discovery of SARS-CoV-2 but positive for other respiratory viruses. Positive RT-qPCR samples were categorized according to their Ct: Ct < 20 (18.7%), ≥ 20-< 25 (27.3%), ≥ 25-< 30 (18.7%), ≥ 30-35 (17.3%), and > 35 (18.0%). Sensitivities (95% confidence interval) for Ct below 25 were 95.7% (92.4-98.9), 97.1% (94.4-99.8), and 97.1% (94.4-99.8) for GSD NovaGen, Bio-Rad, and Aegle, respectively but drastically dropped when Ct exceeded 27. Among samples with previously diagnosed viruses, seven false-positive results were found with GSD NovaGen only (specificity 85.7%). Equivalent, high sensitivities were observed with the highest viral load samples. The GSD NovaGen assay showed less specificity. Although the three kits tested in this study are inadequate for routine testing in a high throughput laboratory, they can help to quickly identify the most infectious patients and screen their close contacts in an environment where molecular tests are not readily available.


Assuntos
Teste Sorológico para COVID-19 , COVID-19/diagnóstico , Testes Imediatos , SARS-CoV-2/isolamento & purificação , Carga Viral , Antígenos Virais/análise , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19/estatística & dados numéricos , Humanos , RNA Viral/análise , RNA Viral/genética , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Sensibilidade e Especificidade
11.
BMC Public Health ; 21(1): 635, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794817

RESUMO

BACKGROUND: Mental health disorders appear as a growing problem in urban areas. While common mental health disorders are generally linked to demographic and socioeconomic factors, little is known about the interaction with the urban environment. With growing urbanization, more and more people are exposed to environmental stressors potentially contributing to increased stress and impairing mental health. It is therefore important to identify features of the urban environment that affect the mental health of city dwellers. The aim of this study was to define associations of combined long-term exposure to air pollution, noise, surrounding green at different scales, and building morphology with several dimensions of mental health in Brussels. METHODS: Research focuses on the inhabitants of the Brussels Capital Region older than 15 years. The epidemiological study was carried out based on the linkage of data from the national health interview surveys (2008 and 2013) and specifically developed indicators describing each participant's surroundings in terms of air quality, noise, surrounding green, and building morphology. These data are based on the geographical coordinates of the participant's residence and processed using Geographical Information Systems (GIS). Mental health status was approached through several validated indicators: the Symptom Checklist-90-R subscales for depressive, anxiety and sleeping disorders and the 12-Item General Health Questionnaire for general well-being. For each mental health outcome, single and multi-exposure models were performed through multivariate logistic regressions. RESULTS: Our results suggest that traffic-related air pollution (black carbon, NO2, PM10) exposure was positively associated with higher odds of depressive disorders. No association between green surrounding, noise, building morphology and mental health could be demonstrated. CONCLUSIONS: These findings have important implications because most of the Brussel's population resides in areas where particulate matters concentrations are above the World Health Organization guidelines. This suggests that policies aiming to reduce traffic related-air pollution could also reduce the burden of depressive disorders in Brussels.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Bélgica/epidemiologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Humanos , Saúde Mental
12.
Genes (Basel) ; 12(4)2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33924636

RESUMO

For 1 year now, the world is undergoing a coronavirus disease-2019 (COVID-19) pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The most widely used method for COVID-19 diagnosis is the detection of viral RNA by RT-qPCR with a specific set of primers and probe. It is important to frequently evaluate the performance of these tests and this can be done first by an in silico approach. Previously, we reported some mismatches between the oligonucleotides of publicly available RT-qPCR assays and SARS-CoV-2 genomes collected from GISAID and NCBI, potentially impacting proper detection of the virus. In the present study, 11 primers and probe sets investigated during the first study were evaluated again with 84,305 new SARS-CoV-2 unique genomes collected between June 2020 and January 2021. The lower inclusivity of the China CDC assay targeting the gene N has continued to decrease with new mismatches detected, whereas the other evaluated assays kept their inclusivity above 99%. Additionally, some mutations specific to new SARS-CoV-2 variants of concern were found to be located in oligonucleotide annealing sites. This might impact the strategy to be considered for future SARS-CoV-2 testing. Given the potential threat of the new variants, it is crucial to assess if they can still be correctly targeted by the primers and probes of the RT-qPCR assays. Our study highlights that considering the evolution of the virus and the emergence of new variants, an in silico (re-)evaluation should be performed on a regular basis. Ideally, this should be done for all the RT-qPCR assays employed for SARS-CoV-2 detection, including also commercial tests, although the primer and probe sequences used in these kits are rarely disclosed, which impedes independent performance evaluation.


Assuntos
Teste de Ácido Nucleico para COVID-19/métodos , COVID-19/virologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , SARS-CoV-2/genética , Simulação por Computador , Genoma Viral , Humanos , Mutação , Sondas RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
13.
Diagn Microbiol Infect Dis ; 100(2): 115326, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33581424

RESUMO

The cobas® Liat® Influenza A/B and respiratory syncytial virus assay was tested on nasopharyngeal aspirates. The resolution of invalid samples was performed using a preanalytical step. cobas® Liat® can be used on nasopharyngeal aspirates with a preanalytical processing step, with a slightly diminished performances in detecting respiratory syncytial virus but not for influenza.


Assuntos
Vírus da Influenza A/isolamento & purificação , Vírus da Influenza B/isolamento & purificação , Influenza Humana/diagnóstico , Nasofaringe/virologia , Infecções por Vírus Respiratório Sincicial/diagnóstico , Vírus Sinciciais Respiratórios/isolamento & purificação , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Testes Imediatos , Infecções por Vírus Respiratório Sincicial/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos
14.
Arch Pharm (Weinheim) ; 354(6): e2000479, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33586249

RESUMO

A concise and versatile synthetic strategy for the total synthesis of arylnaphthalene lignans and aza-analogs was developed. The main objective was to develop synthetic tactics for the creation of the lactone and lactam unit that would give access to an array of synthetic, natural, and/or bioactive compounds through rather simple chemical manipulation. The flexibility and potentiality of these new processes were further illustrated by the total synthesis of retrojusticidin B (13b), justicidin C (14b), and methoxy-vitedoamine A (22a). In this study, a series of novel aryl-naphthalene lignans and aza-analogs were synthesized, and the cytotoxic activities of all compounds on cancer cell growth were evaluated. The target compounds were structurally characterized by 1 H NMR (nuclear magnetic resonance), 13 C NMR, infrared, high-resolution mass spectrometry, and X-ray crystallography. The IC50 values of these compounds on five tumor cell lines (A549, HS683, MCF-7, SK-MEL-28, and B16-F1) were obtained by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric assay. Five of the compounds exhibited excellent activity compared to 5-fluorouracil and etoposide against the five cell lines tested, with IC50 values ranging from 1 to 10 µM.

15.
Environ Int ; 148: 106365, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33444880

RESUMO

BACKGROUND: Epidemiological studies suggest that residing close to green space reduce mortality rates. We investigated the relationship between long-term exposure to residential green space and non-accidental and cardio-respiratory mortality. METHODS: We linked the Belgian 2001 census to population and mortality register follow-up data (2001-2011) among adults aged 30 years and older residing in the five largest urban areas in Belgium (n = 2,185,170 and mean follow-up time 9.4 years). Residential addresses were available at baseline. Exposure to green space was defined as 1) surrounding greenness (2006) [normalized difference vegetation index (NDVI) and modified soil-adjusted vegetation index (MSAVI2)] within buffers of 300 m, 500 m, and 1000 m; 2) surrounding green space (2006) [Urban Atlas (UA) and CORINE Land Cover (CLC)] within buffers of 300 m, 500 m, and 1000 m; and 3) perceived neighborhood green space (2001). Cox proportional hazards models with age as the underlying time scale were used to probe into cause-specific mortality (non-accidental, respiratory, COPD, cardiovascular, ischemic heart disease (IHD), and cerebrovascular). Models were adjusted for several sociodemographic variables (age, sex, marital status, country of birth, education level, employment status, and area mean income). We further adjusted our main models for annual mean (2010) values of ambient air pollution (PM2.5, PM10, NO2 and BC, one at a time), and we additionally explored potential mediation with the aforementioned pollutants. RESULTS: Higher degrees of residential green space were associated with lower rates of non-accidental and respiratory mortality. In fully adjusted models, hazard ratios (HR) per interquartile range (IQR) increase in NDVI 500 m buffer (IQR: 0.24) and UA 500 m buffer (IQR: 0.31) were 0.97 (95%CI 0.96-0.98) and 0.99 (95%CI 0.98-0.99) for non-accidental mortality, and 0.95 (95%CI 0.93-0.98) and 0.97 (95%CI 0.96-0.99) for respiratory mortality. For perceived neighborhood green space, HRs were 0.93 (95%CI 0.92-0.94) and 0.94 (95%CI 0.91-0.98) for non-accidental and respiratory mortality, respectively. The observed lower mortality risks associated with residential exposure to green space were largely independent from exposure to ambient air pollutants. CONCLUSION: We observed evidence for lower mortality risk in associations with long-term residential exposure to green space in most but not all studied causes of death in a large representative cohort for the five largest urban areas in Belgium. These findings support the importance of the availability of residential green space in urban areas.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Adulto , Bélgica/epidemiologia , Censos , Estudos de Coortes , Exposição Ambiental/análise , Seguimentos , Humanos , Parques Recreativos , Material Particulado
17.
Euro Surveill ; 25(39)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33006303

RESUMO

BackgroundRespiratory syncytial virus (RSV) is a common cause of severe respiratory illness in young children (< 5 years old) and older adults (≥ 65 years old) leading the World Health Organization (WHO) to recommend the implementation of a dedicated surveillance in countries.AimWe tested the capacity of the severe acute respiratory infection (SARI) hospital network to contribute to RSV surveillance in Belgium.MethodsDuring the 2018/19 influenza season, we started the SARI surveillance for influenza in Belgium in week 40, earlier than in the past, to follow RSV activity, which usually precedes influenza virus circulation. While the WHO SARI case definition for influenza normally used by the SARI hospital network was employed, flexibility over the fever criterion was allowed, so patients without fever but meeting the other case definition criteria could be included in the surveillance.ResultsBetween weeks 40 2018 and 2 2019, we received 508 samples from SARI patients. We found an overall RSV detection rate of 62.4% (317/508), with rates varying depending on the age group: 77.6% in children aged < 5 years (253/326) and 34.4% in adults aged ≥ 65 years (44/128). Over 90% of the RSV-positive samples also positive for another tested respiratory virus (80/85) were from children aged < 5 years. Differences were also noted between age groups for symptoms, comorbidities and complications.ConclusionWith only marginal modifications in the case definition and the period of surveillance, the Belgian SARI network would be able to substantially contribute to RSV surveillance and burden evaluation in children and older adults, the two groups of particular interest for WHO.


Assuntos
Febre/virologia , Hospitalização/estatística & dados numéricos , Influenza Humana/epidemiologia , Infecções por Vírus Respiratório Sincicial/diagnóstico , Vírus Sincicial Respiratório Humano/isolamento & purificação , Infecções Respiratórias/epidemiologia , Adolescente , Adulto , Idoso , Bélgica/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Infecções por Vírus Respiratório Sincicial/epidemiologia , Fatores de Risco , Estações do Ano , Vigilância de Evento Sentinela , Adulto Jovem
18.
Int J Mol Sci ; 21(15)2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32759818

RESUMO

The current COronaVIrus Disease 2019 (COVID-19) pandemic started in December 2019. COVID-19 cases are confirmed by the detection of SARS-CoV-2 RNA in biological samples by RT-qPCR. However, limited numbers of SARS-CoV-2 genomes were available when the first RT-qPCR methods were developed in January 2020 for initial in silico specificity evaluation and to verify whether the targeted loci are highly conserved. Now that more whole genome data have become available, we used the bioinformatics tool SCREENED and a total of 4755 publicly available SARS-CoV-2 genomes, downloaded at two different time points, to evaluate the specificity of 12 RT-qPCR tests (consisting of a total of 30 primers and probe sets) used for SARS-CoV-2 detection and the impact of the virus' genetic evolution on four of them. The exclusivity of these methods was also assessed using the human reference genome and 2624 closely related other respiratory viral genomes. The specificity of the assays was generally good and stable over time. An exception is the first method developed by the China Center for Disease Control and prevention (CDC), which exhibits three primer mismatches present in 358 SARS-CoV-2 genomes sequenced mainly in Europe from February 2020 onwards. The best results were obtained for the assay of Chan et al. (2020) targeting the gene coding for the spiking protein (S). This demonstrates that our user-friendly strategy can be used for a first in silico specificity evaluation of future RT-qPCR tests, as well as verifying that the former methods are still capable of detecting circulating SARS-CoV-2 variants.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/diagnóstico , Genoma Viral , Pneumonia Viral/diagnóstico , RNA Viral/metabolismo , Reação em Cadeia da Polimerase em Tempo Real/métodos , Betacoronavirus/isolamento & purificação , COVID-19 , Infecções por Coronavirus/virologia , Bases de Dados Genéticas , Humanos , Fases de Leitura Aberta/genética , Pandemias , Pneumonia Viral/virologia , Polimorfismo de Nucleotídeo Único , RNA Viral/análise , RNA Polimerase Dependente de RNA/genética , SARS-CoV-2 , Sensibilidade e Especificidade , Sequenciamento Completo do Genoma
20.
Curr Org Synth ; 17(3): 224-229, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32091341

RESUMO

New substituted 1,4-naphthoquinones have been prepared in good overall yields through the naphthol route. The cytotoxicity of these compounds was tested in vitro on MCF-7 breast tumor cells. The most active compound 14 displayed an IC50 of 15µM. OBJECTIVE: To investigate the cytotoxicity of new naphthoquinones derivatives on MCF-7 cells. METHODS: Synthesis of new naphtoquinones derivatives and in vitro evaluation of their cytotoxicity on MCF-7 cells (rezasurin cell-based assay). RESULTS: Starting from Ethyl 4-hydroxy-6,7-dimethoxy-2-naphthoate, four naphthoquinones were prepared and exhibited substantial cytotoxicity against MCF-7 cells. CONCLUSION: Preliminary studies of the structure-activity relationship have shown the influence of the structural parameters and, in particular, the nature of the naphthoquinone side chain.


Assuntos
Antineoplásicos/farmacologia , Naftoquinonas/farmacologia , Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células MCF-7 , Estrutura Molecular , Naftoquinonas/síntese química , Relação Estrutura-Atividade
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