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RATIONALE: The pathophysiologic mechanisms of air pollution-associated exacerbation of cardiovascular events remain incompletely understood. OBJECTIVE: To assess whether ambient air pollution can be a trigger of the vulnerable plaque and heightened thrombogenicity through systemic inflammatory pathways. METHODS AND RESULTS: In Beijing AIRCHD study (Air Pollution and Cardiovascular Dysfunctions in Healthy Adults Living in Beijing), 73 healthy adults (mean±SD, 23.3±5.4 years) were followed up in 2014 to 2016. We estimated associations between air pollutants and biomarkers relevant to atherosclerotic plaque vulnerability, thrombogenicity, and inflammation using linear mixed-effects models and elucidated the biological pathways involved using mediation analyses. Receiver operating characteristic analyses were conducted to assess the ability of each biomarker to predict ambient air pollution exposures. High average concentrations of particulate matter in diameter <2.5 µm (91.8±63.8 µg/m3) were observed during the study period. Significant increases in circulating biomarkers of plaque vulnerability, namely MMPs (matrix metalloproteinases; MMP-1, 2, 3, 7, 8, and 9), of 8.6% (95% CI, 0.1-17.8) to 141.4% (95% CI, 111.8-171.0) were associated with interquartile range increases in moving averages of particulate matter in diameter <2.5 µm, number concentrations of particles in sizes of 5 to 560 nm and black carbon, during the last 1 to 7 days before each participant's clinic visit. Higher air pollutant levels were also significantly associated with decreases in TIMP (tissue inhibitors of MMPs; TIMP-1 and 2), heightened thrombogenicity (shortened prothrombin time and increases in sCD40L [soluble CD40 ligand], sCD62P [soluble P-selectin], and fibrinogen/fibrin degradation products), and elevations in systemic inflammation (IL-1ß [interleukin-1ß], CRP [C-reactive protein], MIP-1α/ß [macrophage inflammatory protein-1α/ß], sRAGE [soluble receptor for advanced glycation end products], and IGFBP [insulin-like growth factor-binding protein]-1 and 3). Receiver operating characteristic curves showed that several biomarkers can serve as robust pollutant-specific predictors with high versus low black carbon exposure (area under the receiver operating characteristic curve of 0.974 [95% CI, 0.955-0.992] for MMP-8 and 0.962 [95% CI, 0.935-0.988] for sRAGE). Mediation analysis further showed that systemic inflammation can mediate ≤46% of the changes in MMPs and thrombogenicity associated with interquartile range increases in air pollutants. CONCLUSIONS: Our results suggest that air pollution may prompt cardiovascular events by triggering vulnerable plaque along with heightened thrombogenicity possibly through systemic inflammatory pathways.
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Poluentes Atmosféricos/efeitos adversos , Aterosclerose/sangue , Exposição Ambiental/efeitos adversos , Mediadores da Inflamação/sangue , Placa Aterosclerótica , Trombose/sangue , Adolescente , Adulto , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Pequim/epidemiologia , Biomarcadores/sangue , Plaquetas/metabolismo , Citocinas/sangue , Feminino , Humanos , Masculino , Metaloproteinases da Matriz/sangue , Prognóstico , Medição de Risco , Fatores de Risco , Ruptura Espontânea , Trombose/diagnóstico , Trombose/epidemiologia , Fatores de Tempo , Adulto JovemRESUMO
The molecular mechanisms of air pollution-associated adverse cardiovascular effects remain largely unknown. In the present study, we investigated the impacts of ambient air pollution on vascular function and the potential mediation effects of amino acids in a longitudinal follow-up of 73 healthy adults living in Beijing, China, between 2014 and 2016. We estimated associations between air pollutants and serum soluble intercellular adhesion molecule 1 (sICAM-1) and plasma levels of amino acids using linear mixed-effects models, and elucidated the biological pathways involved using mediation analyses. Higher air pollutant levels were significantly associated with increases in sICAM-1 levels. Metabolomics analysis showed that altered metabolites following short-term air pollution exposure were mainly involved in amino acid metabolism. Significant reductions in levels of plasma alanine, threonine and glutamic acid of 2.1 µM [95% confidence interval (CI): -3.8, -0.3] to 62.0 µM (95% CI: -76.1, -47.9) were associated with interquartile range increases in moving averages of PM2.5, BC, CO and SO2 in 1-7 days prior to clinical visits. Mediation analysis also showed that amino acids can mediate up to 48% of the changes in sICAM-1 associated with increased air pollution exposure. Our results indicated that air pollution may prompt vascular dysfunction through perturbing amino acid metabolism.
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Poluentes Atmosféricos , Poluição do Ar , Adulto , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Aminoácidos , China , Exposição Ambiental/análise , Humanos , Material Particulado/análise , Material Particulado/toxicidadeRESUMO
Objective- We aimed to assess whether exposure to higher levels of ambient air pollution impairs HDL (high-density lipoprotein) function and to elucidate the underlying biological mechanisms potentially involved. Approach and Results- In the Beijing AIRCHD study (Air Pollution and Cardiovascular Dysfunction in Healthy Adults), 73 healthy adults (23.3±5.4 years) were followed-up with 4 repeated study visits in 2014 to 2016. During each visit, ambient air pollution concentrations, HDL function metrics, and parameters of inflammation and oxidative stress were measured. Average daily concentrations of ambient particulate matter in diameter <2.5 µm were 62.9 µg/m3 (8.1-331.0 µg/m3). We observed significant decreases in HDL cholesterol efflux capacity of 2.3% (95% CI, -4.3 to -0.3) to 5.0% (95% CI, -7.6 to -2.4) associated with interquartile range increases in moving average concentrations of particulate matter in diameter <2.5 µm and traffic-related air pollutants (black carbon, nitrogen dioxide, and carbon monoxide) during the 1 to 7 days before each participant's clinic visit. Higher ambient air pollutant levels were also associated with significant reductions in circulating HDL cholesterol and apoA-I (apolipoprotein A-I), as well as elevations in HDL oxidation index, oxidized LDL (low-density lipoprotein), malondialdehyde, and high-sensitivity C-reactive protein. Conclusions- Higher ambient air pollution concentrations were associated with impairments in HDL functionality, potentially because of systemic inflammation and oxidative stress. These novel findings further our understanding of the mechanisms whereby air pollutants promote cardiometabolic disorders.
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Poluição do Ar/efeitos adversos , Lipoproteínas HDL/sangue , Adulto , Apolipoproteína A-I/sangue , Biomarcadores , China , HDL-Colesterol/sangue , Exposição Ambiental , Feminino , Humanos , Inflamação , Lipoproteínas LDL/sangue , Masculino , Conceitos Meteorológicos , Pessoa de Meia-Idade , Estresse Oxidativo , Material Particulado/efeitos adversos , Valores de Referência , População Urbana , Emissões de Veículos , Adulto JovemRESUMO
Airborne transmission is one of the environmental dissemination pathways of antibiotic resistance genes (ARGs), and has critical implications for human exposure through inhalation. In this study, we focused on three regions of China to reveal some unique spatiotemporal features of airborne bacteria and ARGs in fine aerosols (PM2.5): (1) greater seasonal variations in the abundance of bacteria and ARGs in temperate urban Beijing than in the subtropical urban areas of the Yangtze River Delta (YRD) and Pearl River Delta (PRD) regions, with regional disparities in bacterial communities; (2) geographical fingerprints of ARG profiles independent of seasonal cycles and land-use gradients within each region; (3) region-independent associations between the targeted ARGs and limited bacterial genera; (4) common correlations between ARGs and mobile genetic elements (MGEs) across regions; and (5) PM2.5 at the higher end of ARG enrichment across various environmental and human media. The spatiotemporally differentiated bacterial communities and ARG abundances, and the compositions, mobility, and potential hosts of ARGs in the atmosphere have strong implications for human inhalational exposure over spatiotemporal scales. By comparing other contributing pathways for the intake of ARGs (e.g., drinking water and food ingestion) in China and the U.S.A., we identified the region-specific importance of inhalation in China as well as country-specific exposure scenarios. Our study thus highlights the significance of inhalation as an integral part of the aggregate exposure pathways of environmentally disseminated ARGs, which, in turn, may help in the formulation of adaptive strategies to mitigate the exposure risks in China and beyond.
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Antibacterianos , Genes Bacterianos , Bactérias , Pequim , China , Resistência Microbiana a Medicamentos , Humanos , Material ParticuladoRESUMO
BACKGROUND: Ambient air pollution has been associated with acute cardiovascular events; however, the underlying mechanisms remain incompletely understood. We aimed to examine the impacts of ambient air pollutants on cardiac ventricular repolarization in a highly polluted urban region. METHODS: Seventy-three healthy non-smoking young adults (66% female, mean age of 23.3⯱â¯5.4 years) were followed with four repeated 24-h electrocardiogram recordings in 2014-2016 in Beijing, China. Continuous concentrations of ambient particulates in size fractions of 5-560â¯nm diameter, black carbon (BC), nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), and ozone (O3) were measured at a fixed-location air pollution monitoring station. Generalized linear mixed models, with adjustment for individual risk factors, time-varying factors and meteorological parameters, were used to evaluate the effects of air pollution on 5-min segments of heart rate-corrected QT interval (QTc), an index of cardiac ventricular repolarization. RESULTS: During the study period, the mean levels of number concentrations of particulates in size range of 5-560â¯nm (PNC5-560) were 20,711 particles/cm3. Significant increases in QTc of 0.56% (95% CI: 0.27, 0.84) to 1.76% (95% CI: 0.73, 2.79) were associated with interquartile range increases in PNC50-560 at prior 1-5â¯moving average days. Significant increases in QTc were also associated with increases in exposures to traffic-related air pollutants (BC, NO2 and CO), a combustion pollutant SO2, and the secondary pollutant O3. The associations were stronger in participants who were male, overweight, with abdominal obesity, and with higher levels of high-sensitivity C-reactive protein. CONCLUSIONS: Our findings suggest that exposures to higher levels of ambient particulates in small size fractions and traffic pollutants were associated with cardiac repolarization abnormalities in healthy adults, and the cardio-metabolic risks may modify the adverse cardiac effects attributable to air pollution.
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Poluentes Atmosféricos , Poluição do Ar/estatística & dados numéricos , Cardiopatias Congênitas/epidemiologia , Ozônio , Adolescente , Adulto , Pequim , China/epidemiologia , Feminino , Humanos , Masculino , Dióxido de Nitrogênio , Material Particulado , Dióxido de Enxofre , Adulto JovemRESUMO
Polycyclic aromatic hydrocarbons (PAHs) have been of health concern due to its carcinogenesis and mutagenesis. In this study, we aimed to assess the variations, sources, and lifetime excessive cancer risk (ECR) attributable to PAHs bound to ambient particulate matters with aerodynamic diameter less than 2.5µm (PM2.5) in metropolitan Beijing, China. We collected 24-hour integrated PM2.5 samples on daily basis between November 2014 and June 2015 across both central heating (cold months) and non-heating (warm months) seasons, and further analyzed the PAH components in these daily PM2.5 samples. Our results showed that total concentrations of PM2.5-bound PAHs varied between (88.6±75.4)ng/m3 in the cold months and (11.0±5.9)ng/m3 in the warm months. Benzo[a]pyrene (BaP), the carcinogenic marker of PAHs, averaged at 5.7 and 0.4ng/m3 in the cold and warm months, respectively. Source apportionment analyses illustrated that gasoline, biomass burning, diesel, coal combustion and cooking were the major contributors, accounting for 12.9%, 17.8%, 24.7%, 24.3% and 6.4% of PM2.5-bound PAHs, respectively. The BaP equivalent lifetime ECR from inhalation of PM2.5-bound PAHs was 16.2 cases per million habitants. Our results suggested that ambient particulate reduction from energy reconstruction and adaption of clean fuels would result in reductions PM2.5-bound PAHs and its associated cancer risks. However, as only particulate phased PAHs was analyzed in the present study, the concentration of ambient PAHs could be underestimated.
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Poluentes Atmosféricos/análise , Poluentes Atmosféricos/química , Monitoramento Ambiental , Material Particulado/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/química , Estações do Ano , Poluentes Atmosféricos/toxicidade , Pequim , Humanos , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Medição de RiscoRESUMO
BACKGROUND: Adverse cardiovascular effects associated with air pollution exposure have been widely demonstrated. However, inconsistent cardiovascular responses were observed from reducing indoor air pollution exposure. We aimed to assess whether short-term air filtration intervention could benefit cardiovascular health in elderly living in high pollution area. METHODS: A randomized crossover intervention study of short-term indoor air filtration intervention on cardiovascular health was conducted among 35 non-smoking elderly participants living in Beijing in the winter of 2013, as part of Beijing Indoor Air Purifier StudY (BIAPSY). Portable air filtration units were randomly allocated to active filtration for 2 weeks and sham filtration for 2 weeks in the households. Twelve-hour daytime ambulatory heart rate variability (HRV) and blood pressure (ABP) were measured during active and sham filtration. Concurrently, real-time indoor and outdoor particulate matter with diameter less than 2.5⯵m (PM2.5) and indoor black carbon (BC) concentrations were measured. We applied generalized additive mixed models to evaluate the associations of 1- to 10-h moving average (MA) exposures of indoor PM2.5 and BC with HRV and ABP indices, and to explore whether these associations could be modified by air filtration. RESULTS: We observed decreases of 34.8% in indoor PM2.5 and 35.3% in indoor BC concentrations during active filtration. Indoor PM2.5 and BC exposures were significantly associated with reduced HRV and increased ABP indices, and greater changes were observed during sham filtration. In specific, each 10⯵g/m3 increase in indoor PM2.5 at MA8-h was associated with a significant reduction of 1.34% (95% CI: -2.42, -0.26) in SDNN during sham filtration, compared with a non-significant reduction of 0.81% (95% CI: -6.00, 4.68) during active filtration (Pinter<â¯0.001). Each 1⯵g/m3 increase in indoor BC at MA8-h was associated with a significant increase of 2.41% (95% CI: 0.38, 4.47) in SBP during sham filtration, compared with a non-significant increase of -1.09% (95% CI: -4.06, 1.96) during active filtration (Pinter =â¯0.135). Nonlinear inverse exposure-response relationships of indoor air pollution exposures with predicted HRV and ABP indices also confirmed some cardiovascular benefits of short-term air filtration intervention. CONCLUSIONS: Our results suggested that short-term indoor air filtration intervention can be of some cardiovascular benefits in elderly living with high pollution episodes.
Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Poluição do Ar , Idoso , Poluição do Ar/efeitos adversos , Poluição do Ar em Ambientes Fechados/efeitos adversos , Poluição do Ar em Ambientes Fechados/estatística & dados numéricos , Pequim , Humanos , Material Particulado/toxicidade , Distribuição AleatóriaRESUMO
With rapid economic development and urbanization in recent decades, China has experienced the worsening of ambient air quality. For better air quality management to protect human health, Chinese government revised national ambient air quality standards (NAAQS) for particulate matter (PM) in 2012 (GB3095-2012). To assess the effectiveness of current NAAQS for PM on public health in Chinese population, we conducted a meta-analysis on published studies examining the mortality risk of short-term exposure to PM with aerodynamic diameters less than 10 and 2.5µm (PM10 and PM2.5) in China. The reported 24-hour concentrations of PM10 and PM2.5 in studies ranged from 43.5 to 150.1µg/m3 and 37.5 to 176.7µg/m3. In the pooled excess, mortality risk estimates of short-term exposure to PM. In specific, per 10µg/m3 increase in PM10, we observed increases of 0.40% (95%CI: 0.33%, 0.47%), 0.57% (95%CI: 0.44%, 0.70%) and 0.49% (95%CI: 0.40%, 0.58%) in total, respiratory and cardiovascular mortality, per 10µg/m3 increase in PM2.5, we observed increases of 0.51% (95%CI: 0.38%, 0.63%), 0.62% (95%CI: 0.52%, 0.73%) and 0.75% (95%CI: 0.54%, 0.95%) in total, respiratory and cardiovascular mortality. Finally, we derived 125µg/m3 for PM10 and 62.5µg/m3 for PM2.5 as 24-hour recommendation values based on the pooled estimates. Our results indicated that current Chinese NAAQS for PM could be sufficient in mitigating the excess mortality risk from short-term exposure to ambient PM. However, future research on long-term exposure cohort studies in Chinese population is also essential in revising annual averages for PM in Chinese NAAQS.
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Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , Exposição Ambiental/estatística & dados numéricos , Material Particulado/análise , Poluentes Atmosféricos/normas , China , Monitoramento Ambiental , Humanos , Material Particulado/normas , Saúde Pública , Padrões de Referência , UrbanizaçãoRESUMO
BACKGROUND/AIMS: Our previous study showed that exposure to a 50-Hz magnetic field (MF) could induce transient mitochondrial permeability transition (MPT) in cells. In the present study, the aim was to explore the possible biological implications of MF-induced transient MPT. MATERIALS AND METHODS: Human amniotic (FL) cells were exposed to MF for different durations or intensities followed by incubation with staurosporine for 4 h. After MF exposure, cell early apoptosis, cell viability mitochondrial ROS and the level of phosphorylated Akt were assessed. After MF exposure followed by incubation with staurosporine, cell early apoptosis was assessed. RESULTS: MF exposure had a protective effect against early apoptosis induced by staurosporine, which could be abolished by MPT inhibitors, although MF exposure alone had no significant effect on early apoptosis or viability of cells. In addition, exposing cells to MF increased the level of mitochondrial ROS which were released into cytoplasm through mitochondrial permeability transition pores (mPTP), and induced ROS-dependent phosphorylation of Akt. Furthermore, the anti-apoptotic effect of MF exposure was completely eliminated when Akt was inhibited. CONCLUSIONS: The present study indicated a possibility that mitochondrial ROS release through mPTP and subsequent Akt activation were necessary for the anti-apoptotic effect of MF.
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Líquido Amniótico/citologia , Apoptose , Campos Magnéticos , Mitocôndrias/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular , Sobrevivência Celular , Ativação Enzimática , Humanos , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Poro de Transição de Permeabilidade MitocondrialRESUMO
Previously, we found that exposure to a 50-Hz magnetic field (MF) could induce epidermal growth factor receptor (EGFR) clustering and phosphorylation on cell surface. In order to explore the possible mechanisms, the roles of acid sphingomyelinase (ASMase) and lipid raft in MF-induced EGFR clustering were investigated in the present study. Human amnion epithelial (FL) cells were exposed to a 50-Hz MF at 0.4 mT for different durations. Intracellular ASMase activity was detected using the Amplex® Red Sphingomyelinase Assay Kit. EGFR clustering, ASMase, and lipid rafts on cell membrane were analyzed using confocal microscopy after indirect immunofluorescence staining. Results showed that disturbing lipid rafts with nystatin could inhibit MF-induced EGFR clustering, indicating that it was dependent on intact lipid raft. Exposure of FL cells to MF significantly enhanced ASMase activity and induced ASMase translocation to membrane that co-localized with lipid rafts. Treatment with imipramine, an ASMase inhibitor, inhibited the MF-induced EGFR clustering. This inhibitory effect could be blocked by the addition of C2-ceramide in the culture medium. It suggested that ASMase mediated the 50-Hz MF-induced EGFR clustering via ceramide which was produced from hydrolyzation on lipid rafts.
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Receptores ErbB/metabolismo , Microdomínios da Membrana/metabolismo , Esfingomielina Fosfodiesterase/metabolismo , Âmnio/citologia , Âmnio/efeitos da radiação , Células Epiteliais/enzimologia , Células Epiteliais/efeitos da radiação , Humanos , Imipramina , Campos Magnéticos , Microdomínios da Membrana/efeitos da radiação , Fosforilação , Esfingomielina Fosfodiesterase/antagonistas & inibidores , Esfingomielina Fosfodiesterase/genética , Esfingosina/administração & dosagem , Esfingosina/análogos & derivadosRESUMO
Self-collection of saliva samples has attracted considerable attention in recent years, particularly during the coronavirus disease 2019 pandemic. However, studies investigating the detection of other common respiratory pathogens in saliva samples are limited. In this study, nasopharyngeal swabs (NPS), oropharyngeal swabs (OPS), and "hock-a-loogie" saliva (HLS) were collected from 469 patients to detect 13 common respiratory pathogens. Overall positivity rates for NPS (66.1 %), HLS (63.5 %), and OPS (57.8 %) were statistically different (P = 0.028), with an overall concordance of 72.7 %. Additionally, detection rates for NPS (85.9 %) and HLS (83.2 %) for all pathogens were much higher than for OPS (73.3 %). Coronavirus and human rhinovirus were most frequently detected pathogens in NPS (P < 0.001). Mycoplasma pneumoniae was significantly more prevalent in the HLS group (P = 0.008). In conclusion, NPS was a reliable sample type for detecting common respiratory pathogens. HLS was more easily collected and can be used in emergencies or specific conditions. Mixed NPS/OPS and NPS/HLS specimens have the potential to improve detection rates, although OPS testing alone has a relatively high risk for missed detection.
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An increasing number of works have highlighted the importance of metal implants surface modification in enhancing bone defect healing through the synergistic osteogenesis-angiogenesis regulation. Studies have shown that pitavastatin has the effect of promoting osteogenesis and angiogenesis. However, how to prepare pitavastatin functionalized implants and how pitavastatin regulates the synergies of osteogenesis and angiogenesis around implants as well as the related mechanisms remain unclear. In the present study, multilayer films with osteogenic and angiogenic properties were constructed on pure titanium substrates via the layer-by-layer assembly of pitavastatin-loaded ß-cyclodextrin grafted chitosan and gelatin. In vitro experiments demonstrated that locally applied pitavastatin could dramatically enhance osteogenic potential of mesenchymal stem cells (MSCs) and angiogenic potential of endothelial cells (ECs). Moreover, pitavastatin loaded multilayer films could regulate the paracrine signaling mediated crosstalk between MSCs and ECs, and indirectly increase the angiogenic potential of MSCs and osteogenic potential of ECs via multiple paracrine signaling. The results of subcutaneous and femur implantation confirmed that locally released pitavastatin had potentially triggered a chain of biological events: mobilizing endogenous stem cells and ECs to the implant-bone interface, in turn facilitating coupled osteogenesis and angiogenesis, and eventually enhancing peri-implant osseointegration. This study enlarges the application scope of pitavastatin and provides an optional choice for developing a multifunctional bioactive coating on the surfaces of mental implants.
Assuntos
Osseointegração , Osteogênese , Diferenciação Celular , Células Endoteliais , Quinolinas , Propriedades de Superfície , Titânio/química , Titânio/farmacologiaRESUMO
Epidemiological evidence linking metals bound to ambient particulate matters with aerodynamic diameter less than 2.5 µm (PM2.5) and maternal thyroid function is limited. In this study, we investigated the association of PM2.5-bound metals with maternal thyroid hormones (TH) during the first trimester. We retrospectively reviewed data for 2528 pregnant women attending prenatal care in Jinhua Maternal and Child Health Care Hospital, Jinhua, China, from January to December 2018. Information including thyroid hormone levels and demographics was retrieved from existing medical records. We analyzed the concentration of 10 metals for collected particulate samples, and estimated their exposure levels during the first trimester for each woman. We employed multivariate linear regression models to estimate the association of exposure to individual PM2.5-bound metals with serum levels of maternal TH, and weighted quantile sum (WQS) to estimate the overall association of exposure to PM2.5-bound metals within a mixture. Higher exposures to most of the PM2.5-bound metals were associated with lower levels of maternal free thyroxine (FT4) and free triiodothyronine (FT3). The thyroid peroxidase antibody (TPOAb) or thyroglobulin antibody (TgAb) status had no effect modification on the observed associations. WQS analyses further suggested that Be, Ni, Tl and Ba contributed the most to the associations. These findings highlight the associations of exposure to PM2.5-bound metals with maternal thyroid function, and emphasize the public health significance of commitments to improve air quality.
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Poluição do Ar , Glândula Tireoide , Criança , Feminino , Humanos , Exposição Materna , Material Particulado , Gravidez , Estudos RetrospectivosRESUMO
BACKGROUND: Severe disease of COVID-19 and mortality occur more frequently in male patients than that in female patients may be related to testosterone level. However, the diagnostic value of changes in the level of testosterone in predicting severe disease of male COVID-19 patients has not been determined yet. METHODS: Sixty-one male COVID-19 patients admitted to the First Affiliated Hospital of Zhejiang University School of Medicine were enrolled. Serum samples at different stages of the patients after admission were collected and testosterone levels were detected to analyze the correlation between testosterone level and disease severity. Transcriptome analysis of PBMC was performed in 34 patients. RESULTS: Testosterone levels at admission in male non-ICU COVID-19 patients (3.7 nmol/L, IQR: 1.5 â¼ 4.7) were significantly lower than those in male ICU COVID-19 patients (6.7 nmol/L, IQR: 4.2 â¼ 8.7). Testosterone levels in the non-ICU group increased gradually during the progression of the disease, while those in the ICU group remained low. In addition, testosterone level of enrolled patients in the second week after onset was significantly correlated with the severity of pneumonia, and ROC curve showed that testosterone level in the second week after onset was highly effective in predicting the severity of COVID-19. Transcriptome studies have found that testosterone levels of COVID-19 patients were associated with immune response, including T cell activation and regulation of lymphocyte activation. In addition, CD28 and Inositol Polyphosphate-4-Phosphatase Type II B (INPP4B) were found positively correlated with testosterone. CONCLUSIONS: Serum testosterone is an independent risk factor for predicting the severity of COVID-19 in male patients, and the level of serum testosterone in the second week after onset is valuable for evaluating the severity of COVID-19. Testosterone level is associated with T cell immune activation. The monitoring of serum testosterone should be highlighted in clinical treatment and the related mechanism should be further studied.
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COVID-19 , Testosterona , Feminino , Perfilação da Expressão Gênica , Humanos , Imunidade , Leucócitos Mononucleares , Masculino , SARS-CoV-2 , Índice de Gravidade de Doença , Linfócitos TRESUMO
The role of respiratory tract microbes and the relationship between respiratory tract and gut microbiomes in coronavirus disease 2019 (COVID-19) remain uncertain. Here, the metagenomes of sputum and fecal samples from 66 patients with COVID-19 at three stages of disease progression are sequenced. Respiratory tract, gut microbiome, and peripheral blood mononuclear cell (PBMC) samples are analyzed to compare the gut and respiratory tract microbiota of intensive care unit (ICU) and non-ICU (nICU) patients and determine relationships between respiratory tract microbiome and immune response. In the respiratory tract, significantly fewer Streptococcus, Actinomyces, Atopobium, and Bacteroides are found in ICU than in nICU patients, while Enterococcus and Candida increase. In the gut, significantly fewer Bacteroides are found in ICU patients, while Enterococcus increases. Significant positive correlations exist between relative microbiota abundances in the respiratory tract and gut. Defensin-related pathways in PBMCs are enhanced, and respiratory tract Streptococcus is reduced in patients with COVID-19. A respiratory tract-gut microbiota model identifies respiratory tract Streptococcus and Atopobium as the most prominent biomarkers distinguishing between ICU and nICU patients. The findings provide insight into the respiratory tract and gut microbial dynamics during COVID-19 progression, considering disease severity, potentially contributing to diagnosis, and treatment strategies.
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COVID-19 , Microbiota , Biomarcadores , Defensinas , Enterococcus , Trato Gastrointestinal , Humanos , Leucócitos Mononucleares , Sistema RespiratórioRESUMO
Epidemiological evidence suggests that patients with hypertension infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are at increased risk of acute lung injury. However, it is still not clear whether this increased risk is related to the usage of renin-angiotensin system (RAS) blockers. We collected medical records of coronavirus disease 2019 (COVID-19) patients from the First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China), and evaluated the potential impact of an angiotensin II receptor blocker (ARB) on the clinical outcomes of COVID-19 patients with hypertension. A total of 30 hypertensive COVID-19 patients were enrolled, of which 17 were classified as non-ARB group and the remaining 13 as ARB group based on the antihypertensive therapies they received. Compared with the non-ARB group, patients in the ARB group had a lower proportion of severe cases and intensive care unit (ICU) admission as well as shortened length of hospital stay, and manifested favorable results in most of the laboratory testing. Viral loads in the ARB group were lower than those in the non-ARB group throughout the disease course. No significant difference in the time of seroconversion or antibody levels was observed between the two groups. The median levels of soluble angiotensin-converting enzyme 2 (sACE2) in serum and urine samples were similar in both groups, and there were no significant correlations between serum sACE2 and biomarkers of disease severity. Transcriptional analysis showed 125 differentially expressed genes which mainly were enriched in oxygen transport, bicarbonate transport, and blood coagulation. Our results suggest that ARB usage is not associated with aggravation of COVID-19. These findings support the maintenance of ARB treatment in hypertensive patients diagnosed with COVID-19.
Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Anticorpos Antivirais/sangue , COVID-19/complicações , Hipertensão/tratamento farmacológico , Carga Viral , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/efeitos adversos , Enzima de Conversão de Angiotensina 2/sangue , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Biomarcadores , China , Feminino , Humanos , Hipertensão/complicações , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , TranscriptomaRESUMO
Background: Viral nucleic acid detection is considered the gold standard for the diagnosis of coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2 infection. However, unsuitable sample types and laboratory detection kits/methods lead to misdiagnosis, which delays the prevention and control of the pandemic. Methods: We compared four nucleic acid detection methods [two kinds of reverse transcription polymerase chain reactions (RT-PCR A: ORF1ab and N testing; RT-PCRB: only ORF1ab testing), reverse transcription recombinase aided amplification (RT-RAA) and droplet digital RT-PCR (dd-RT-PCR)] using 404 samples of 72 hospitalized COVID-19 patients, including oropharyngeal swab (OPS), nasopharyngeal swabs (NPS) and saliva after deep cough, to evaluate the best sample type and method for SARS-CoV-2 detection. Results: Among the four methods, dd-RT-PCR exhibited the highest positivity rate (93.0%), followed by RT-PCR B (91.2%) and RT-RAA (91.2%), while the positivity rate of RT-PCR A was only 71.9%. The viral load in OPS [24.90 copies/test (IQR 15.58-129.85)] was significantly lower than that in saliva [292.30 copies/test (IQR 20.20-8628.55)] and NPS [274.40 copies/test (IQR 33.10-2836.45)]. In addition, if OPS samples were tested alone by RT-PCR A, only 21.4% of the COVID-19 patients would be considered positive. The accuracy of all methods reached nearly 100% when saliva and NPS samples from the same patient were tested simultaneously. Conclusions: SARS-CoV-2 nucleic acid detection methods should be fully evaluated before use. High-positivity rate methods such as RT-RAA and dd-RT-PCR should be considered when possible. Furthermore, saliva after deep cough and NPS can greatly improve the accuracy of the diagnosis, and testing OPS alone is not recommended.
Assuntos
Teste para COVID-19/métodos , COVID-19 , COVID-19/diagnóstico , Teste de Ácido Nucleico para COVID-19 , Humanos , Nasofaringe , Pandemias , RNA Viral/genética , SARS-CoV-2 , Saliva , Manejo de EspécimesRESUMO
Understanding the transmission mechanism of SARS-CoV-2 is a prerequisite to effective control measures. To investigate the potential modes of SARS-CoV-2 transmission, 21 COVID-19 patients from 12-47 days after symptom onset were recruited. We monitored the release of SARS-CoV-2 from the patients' exhaled breath and systematically investigated environmental contamination of air, public surfaces, personal necessities, and the drainage system. SARS-CoV-2 RNA was detected in 0 of 9 exhaled breath samples, 2 of 8 exhaled breath condensate samples, 1 of 12 bedside air samples, 4 of 132 samples from private surfaces, 0 of 70 samples from frequently touched public surfaces in isolation rooms, and 7 of 23 feces-related air/surface/water samples. The maximum viral RNA concentrations were 1857 copies/m3 in the air, 38 copies/cm2 in sampled surfaces and 3092 copies/mL in sewage/wastewater samples. Our results suggest that nosocomial transmission of SARS-CoV-2 can occur via multiple routes. However, the low detection frequency and limited quantity of viral RNA from the breath and environmental specimens may be related to the reduced viral load of the COVID-19 patients on later days after symptom onset. These findings suggest that the transmission dynamics of SARS-CoV-2 differ from those of SARS-CoV in healthcare settings.
Assuntos
COVID-19/transmissão , Transmissão de Doença Infecciosa/prevenção & controle , SARS-CoV-2 , Adolescente , Adulto , Idoso , COVID-19/virologia , Infecção Hospitalar/prevenção & controle , Fezes/virologia , Feminino , Fômites/virologia , Hospitais Universitários , Humanos , Controle de Infecções/métodos , Masculino , Pessoa de Meia-Idade , RNA Viral/análise , SARS-CoV-2/química , SARS-CoV-2/isolamento & purificação , Escarro/virologiaRESUMO
Epidemiological evidence on cardiometabolic health of particulate organic matter (POM) and its sources is sparse. In a panel of 73 healthy adults in Beijing, China, daily concentrations of ambient fine particulate matter-bound polycyclic aromatic hydrocarbons (PAHs) and n-alkanes were measured throughout the study period, and Positive Matrix Factorization approach was used to identity PAHs sources. Linear mixed-effect models and mediation analyses were applied to examine the associations and potential interlink pathways between POM and biomarkers indicative of hemodynamics, insulin resistance, vascular calcification and immune inflammation. We found that significant alterations in cardiometabolic measures were associated with POM exposures. In specific, interquartile range increases in PAHs concentrations at prior up to 9 days were observed in association with significant elevations of 2.6-2.9% in diastolic blood pressure, 6.6-8.1% in soluble ST2, 10.5-14.5% in insulin, 40.9-45.7% in osteoprotegerin, and 36.3-48.7% in interleukin-17A. Greater associations were generally observed for PAHs originating from traffic emissions and coal burning. Mediation analyses revealed that POM exposures may prompt the genesis of hemodynamic abnormalities, possibly via worsening insulin resistance and calcification potential. These findings suggested that cardiometabolic health benefits would be achieved by reducing PM from combustion emissions.
Assuntos
Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Adulto , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , China , Monitoramento Ambiental , Hemodinâmica , Humanos , Material Particulado/análise , Material Particulado/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/toxicidadeRESUMO
To clarify the effect of different respiratory sample types on SARS-CoV-2 detection, we collected throat swabs, nasal swabs and hock-a-loogie saliva or sputum, and compared their detection rates and viral loads. The detection rates of sputum (95.65%, 22/23) and hock-a-loogie saliva (88.09%, 37/42) were significantly higher than those in throat swabs (41.54%, 27/65) and nasal swabs (72.31%, 47/65) (P < 0.001). The Ct Values of sputum, hock-a-loogie saliva and nasal swabs were significantly higher than that in throat swabs, whereas no significant difference was observed between sputum and saliva samples. Hock-a-loogie saliva are reliable sample types that can be used to detect SARS-CoV-2, and worthy of clinical promotion.