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1.
Front Immunol ; 14: 1196031, 2023.
Article in English | MEDLINE | ID: covidwho-20236991

ABSTRACT

Swine acute diarrhoea syndrome coronavirus (SADS-CoV), which is a recently discovered enteric coronavirus, is the major aetiological agent that causes severe clinical diarrhoea and intestinal pathological damage in pigs, and it has caused significant economic losses to the swine industry. Nonstructural protein 5, also called 3C-like protease, cleaves viral polypeptides and host immune-related molecules to facilitate viral replication and immune evasion. Here, we demonstrated that SADS-CoV nsp5 significantly inhibits the Sendai virus (SEV)-induced production of IFN-ß and inflammatory cytokines. SADS-CoV nsp5 targets and cleaves mRNA-decapping enzyme 1a (DCP1A) via its protease activity to inhibit the IRF3 and NF-κB signaling pathways in order to decrease IFN-ß and inflammatory cytokine production. We found that the histidine 41 and cystine 144 residues of SADS-CoV nsp5 are critical for its cleavage activity. Additionally, a form of DCP1A with a mutation in the glutamine 343 residue is resistant to nsp5-mediated cleavage and has a stronger ability to inhibit SADS-CoV infection than wild-type DCP1A. In conclusion, our findings reveal that SADS-CoV nsp5 is an important interferon antagonist and enhance the understanding of immune evasion by alpha coronaviruses.


Subject(s)
Alphacoronavirus , Coronavirus , Interferon Type I , Animals , Swine , Alphacoronavirus/genetics , Alphacoronavirus/metabolism , Coronavirus/metabolism , Endopeptidases , Interferon Type I/metabolism
2.
Proc Natl Acad Sci U S A ; 119(41): e2209042119, 2022 10 11.
Article in English | MEDLINE | ID: covidwho-2288486

ABSTRACT

Viruses employ a variety of strategies to escape or counteract immune responses, including depletion of cell surface major histocompatibility complex class I (MHC-I), that would ordinarily present viral peptides to CD8+ cytotoxic T cells. As part of a screen to elucidate biological activities associated with individual severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral proteins, we found that ORF7a reduced cell surface MHC-I levels by approximately fivefold. Nevertheless, in cells infected with SARS-CoV-2, surface MHC-I levels were reduced even in the absence of ORF7a, suggesting additional mechanisms of MHC-I down-regulation. ORF7a proteins from a sample of sarbecoviruses varied in their ability to induce MHC-I down-regulation and, unlike SARS-CoV-2, the ORF7a protein from SARS-CoV lacked MHC-I downregulating activity. A single amino acid at position 59 (T/F) that is variable among sarbecovirus ORF7a proteins governed the difference in MHC-I downregulating activity. SARS-CoV-2 ORF7a physically associated with the MHC-I heavy chain and inhibited the presentation of expressed antigen to CD8+ T cells. Specifically, ORF7a prevented the assembly of the MHC-I peptide loading complex and caused retention of MHC-I in the endoplasmic reticulum. The differential ability of ORF7a proteins to function in this way might affect sarbecovirus dissemination and persistence in human populations, particularly those with infection- or vaccine-elicited immunity.


Subject(s)
Antigen Presentation , CD8-Positive T-Lymphocytes , COVID-19 , Histocompatibility Antigens Class I , Viral Proteins , Amino Acids , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Histocompatibility Antigens Class I/immunology , Humans , Major Histocompatibility Complex , Peptides , SARS-CoV-2 , Viral Proteins/immunology
3.
Sustainability ; 14(15):9623, 2022.
Article in English | ProQuest Central | ID: covidwho-1994192

ABSTRACT

Exploring the spatial network structure of tourism flow and its influencing factors is of great significance to the transmission of characteristic culture and the sustainable development of tourism in tourist destinations, especially in backward rural areas. Taking Qiandongnan Miao and Dong Autonomous Prefecture (hereinafter referred to as Qiandongnan Prefecture) as an example, this paper adopts social network analysis and Quadratic Assignment Procedure regression analysis to study the network structural characteristics and influencing factors of tourism flow using online travel blog data. The results show that: (1) There are seasonal changes in tourism flow, but the attractions that tourists pay attention to do not change with the seasons. (2) The tightness of the tourism flow network structure is poor. The core nodes are unevenly distributed, and there are obvious structural holes. (3) The density of the tourism flow network is low. There is a clear core–periphery structure in the network, and the core area has a weak driving effect on the periphery area. There are more cohesive subgroups in the network, but the degree of connectedness between the subgroups varies greatly. (4) Geographical adjacency, transportation accessibility, and tourism resource endowment influence tourism flow network structure. The study found that the influencing factors of tourism flow in rural areas are different from those in urban areas. These results provide useful information for the marketing and development of tourism management departments in rural areas.

4.
BMJ Open ; 12(3): e059067, 2022 03 25.
Article in English | MEDLINE | ID: covidwho-1765126

ABSTRACT

INTRODUCTION: COVID-19 is a public health emergency of international concern, which is characterised by rapid and widespread transmission, high mortality and complications. Several studies have shown the benefits of tai chi and qigong for recovery after COVID-19; however, no meta-analysis has been reported. Therefore, the purpose of this study is to evaluate the efficacy and safety of tai chi and/or qigong on rehabilitation after COVID-19 through a systematic review and meta-analysis to provide a reference and basis for clinical application. METHODS AND ANALYSIS: This study will use the Cochrane Library, PubMed, Web of Science, Embase, China Knowledge Network, China Biomedical Literature Database, Chinese Scientific Journal Database and Wanfang Database. The time period is from the inception of the database to November 2021, with no language restrictions. Searches will be conducted using the subject terms "Taichi","Qigong" and "COVID-19" plus free-text words. Articles will be screened and collected by two reviewers independently. Included studies will be assessed for quality using the Cochrane Risk of Bias Assessment Tool. Statistical analyses will be performed using the Revman V.5.3 software. The primary outcomes include 1-second forced expiratory volume and 1-second forced vital capacity, oxygen saturation, total white cell count and quality of life score. Secondary outcomes include time to remission of major symptoms, incidence of adverse events, clinical cure rate and mortality. Subgroup and sensitivity analyses will also be used to explore and interpret the heterogeneity. This protocol is written based on the guideline of the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocol. ETHICS AND DISSEMINATION: Ethical approval and consent are unnecessary because no primary data will be collected. The results will be disseminated through peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42021288962.


Subject(s)
COVID-19 , Qigong , Tai Ji , Humans , Meta-Analysis as Topic , Quality of Life , Systematic Reviews as Topic
5.
Pharmacol Res ; 161: 105290, 2020 11.
Article in English | MEDLINE | ID: covidwho-1318948

ABSTRACT

The coronavirus disease 2019 (COVID-19) epidemic has been almost controlled in China under a series of policies, including "early diagnosis and early treatment". This study aimed to explore the association between early treatment with Qingfei Paidu decoction (QFPDD) and favorable clinical outcomes. In this retrospective multicenter study, we included 782 patients (males, 56 %; median age 46) with confirmed COVID-19 from 54 hospitals in nine provinces of China, who were divided into four groups according to the treatment initiation time from the first date of onset of symptoms to the date of starting treatment with QFPDD. The primary outcome was time to recovery; days of viral shedding, duration of hospital stay, and course of the disease were also analyzed. Compared with treatment initiated after 3 weeks, early treatment with QFPDD after less than 1 week, 1-2 weeks, or 2-3 weeks had a higher likelihood of recovery, with adjusted hazard ratio (HR) (95 % confidence interval [CI]) of 3.81 (2.65-5.48), 2.63 (1.86-3.73), and 1.92 (1.34-2.75), respectively. The median course of the disease decreased from 34 days to 24 days, 21 days, and 18 days when treatment was administered early by a week (P < 0.0001). Treatment within a week was related to a decrease by 1-4 days in the median duration of hospital stay compared with late treatment (P<0.0001). In conclusion, early treatment with QFPDD may serve as an effective strategy in controlling the epidemic, as early treatment with QFPDD was associated with favorable outcomes, including faster recovery, shorter time to viral shedding, and a shorter duration of hospital stay. However, further multicenter, prospective studies with a larger sample size should be conducted to confirm the benefits of early treatment with QFPDD.


Subject(s)
COVID-19 Drug Treatment , Drugs, Chinese Herbal/therapeutic use , Adult , Aged , Aged, 80 and over , China , Cohort Studies , Female , Follow-Up Studies , Humans , Length of Stay , Male , Middle Aged , Time-to-Treatment , Treatment Outcome , Young Adult
7.
BMC Infect Dis ; 21(1): 412, 2021 May 04.
Article in English | MEDLINE | ID: covidwho-1216882

ABSTRACT

BACKGROUND: Since the outbreak of coronavirus disease 2019 in December 2019, more than 8 million cases have occurred worldwide as of June 16, 2020. However, it is important to distinguish COVID-19 from other respiratory infectious diseases, such as influenza. Here, we comparatively described the clinical characteristics of children with COVID-19 and paediatric patients with influenza. METHODS: In this retrospective, single-centre study, we reviewed the electronic medical records of 585 paediatric patients with COVID-19 or influenza in Wuhan Children's Hospital, China. Clinical and epidemiological characteristics, laboratory findings, and clinical outcomes were comparatively analysed. RESULTS: The median ages were 6.96 years (IQR, 2-10.81) for children with confirmed COVID-19, 2.67 years (IQR, 1.03-15.25) for those with influenza A and 3.67 years (IQR, 1.62-5.54) for those with influenza B. Fever was a symptom in 84 (34.7%) COVID-19 cases, 132 (70.21%) influenza A cases and 111 (74.50%) influenza B cases. The median length of stay (LOS) was 11 (8-15) days for paediatric COVID-19 patients, 4 (3-6) days for influenza A patients and 5 (3-6) days for influenza B patients. Twenty-six (13.98%) influenza A patients and 18 (12.59%) influenza B patients presented with decreased white blood cell counts, while 13 (5.33%) COVID-19 patients presented with decreased white blood cell counts. Eight (3.28%) COVID-19 patients, 23 (12.71%) influenza A patients and 21 (14.79%) influenza B patients experienced lymphocytopenia. Acute cardiac injury occurred in 18 (7.29%) COVID-19 patients, while 37 (19.68%) influenza A and 27 (18.12%) influenza B patients had acute cardiac injury. CONCLUSION: In this study, the illnesses of children with COVID-19 were demonstrated to be less severe than those of paediatric patients with influenza, and COVID-19 patients had milder illness and fewer complications.


Subject(s)
COVID-19 Drug Treatment , COVID-19/etiology , Influenza, Human/drug therapy , Influenza, Human/etiology , Adolescent , COVID-19/epidemiology , Child , Child, Hospitalized , Child, Preschool , China/epidemiology , Comorbidity , Female , Fever/epidemiology , Hospitals, Pediatric , Humans , Infant , Influenza, Human/epidemiology , Length of Stay , Lymphopenia/epidemiology , Lymphopenia/virology , Male , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/epidemiology , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/virology , Retrospective Studies
8.
Front Pharmacol ; 11: 576994, 2020.
Article in English | MEDLINE | ID: covidwho-1067659

ABSTRACT

Background: At present, the epidemic of the novel coronavirus disease 2019 (COVID-19) has quickly engulfed the world. Inflammatory cytokines are associated with the severity and outcomes of patients with COVID-19. However, the prognostic value of pro-inflammatory factors in cancer patients with COVID-19 are unknown. Methods: A multi-center, retrospective, cross-sectional study, based on five designated tertiary hospitals for the treatment of COVID-19 in Hubei Province, China. 112 cancer patients with COVID-19, and 105 COVID-19 patients without cancer were enrolled in the study between January 1st, 2020 and April 30th, 2020. The risk assessment of pro-inflammatory factors for disease severity and clinical adverse outcomes was identified by univariable and multivariable logistic regression models. Results: Of the 112 cancer patients with COVID-19, 40 (35.7%) patients were in critical condition and 18 (16.1%) patients died unfortunately. Univariate and multivariate analysis demonstrated that hemoglobin level and pro-inflammatory neutrophils and C-reactive protein (CRP), can be used as independent factors affecting the severity of COVID-19; Meanwhile, pro-inflammatory neutrophils and CRP can be used as an independent influencing factor for adverse clinical outcome of death. Moreover, the dynamic changes of neutrophils and CRP were also presented, and compared with COVID-19 patients without cancer, cancer patients with COVID-19 showed higher neutrophil counts and CRP levels. Conclusion: In cancer patients with COVID-19, the significant increase in pro-inflammatory neutrophils and CRP indicated a more critical illness and adverse clinical outcome, and pro-inflammatory neutrophils and CRP played a greater adverse role compare with COVID-19 patients without cancer, which may be the cause of critical illness and adverse clinical outcomes of cancer patients with COVID-19.

9.
Biomed Environ Sci ; 33(12): 893-905, 2020 Dec 20.
Article in English | MEDLINE | ID: covidwho-1060079

ABSTRACT

OBJECTIVE: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. METHODS: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( OR) and 95% confidence interval (95% CI) of the associations between comorbidities (cardiometabolic or non-cardiometabolic diseases), clinical severity, and treatment outcomes of COVID-19. RESULTS: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. CONCLUSION: Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.


Subject(s)
COVID-19/complications , Adult , Aged , COVID-19/epidemiology , COVID-19/therapy , COVID-19/virology , China/epidemiology , Comorbidity , Female , Humans , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Treatment Outcome
10.
Front Oncol ; 10: 570130, 2020.
Article in English | MEDLINE | ID: covidwho-922796

ABSTRACT

Since December 2019, a novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly engulfed the world. Cancer patients infected with COVID-19 are considered to carry higher severity of the disease and higher mortality rate than common COVID-19 patients in previous studies. However, due to the poor clinical information on COVID-19 patients with cancer, the evidences that supported this conclusion are insufficient. At present, rather limited reports have analyzed the clinical data of breast cancer patients infected with COVID-19. Therefore, in this retrospective study, we described the clinical characteristics and the outcomes of 35 COVID-19 patients with breast cancer and compared 55 COVID-19 patients without cancer and 81 COVID-19 patients with other types of cancer as controls. Our data showed that there were no differences in disease severity and outcomes between the COVID-19 patients with breast cancer and the common COVID-19 patients, which was in contrast to previous studies. In addition, compared with other types of cancer patients, asymptomatic infections and mild cases among breast cancer patients made up a substantially larger proportion. Our results indicated that the clinical characteristics of breast cancer patients were milder than those of other types of cancer patients, but there were no significant differences in outcomes between the two groups.

11.
J Infect Dis ; 222(8): 1293-1297, 2020 09 14.
Article in English | MEDLINE | ID: covidwho-811301

ABSTRACT

The number of coronavirus disease 2019 (COVID-19) cases has exceeded 10 million. However, little is known about the epidemiology and clinical characteristics of COVID-19 infants. We collected medical information of 46 confirmed patients (<1 year old) and retrospectively analyzed epidemiological history, clinical symptoms, and laboratory test results. The median age was 5 (interquartile range, 2-7) months. Sixteen cases had fever and 27 cases had cough. Moderate disease was present in 40 cases and cardiac injury occurred in 38 cases, following by liver dysfunction in 20 cases and lymphocytosis in no cases. Of all infant patients, 2 received invasive mechanical ventilation and 1 died with multiple organ dysfunction syndrome.


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Age Factors , Betacoronavirus/isolation & purification , COVID-19 , China/epidemiology , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , Cough/therapy , Cough/virology , Female , Fever/therapy , Fever/virology , Humans , Infant , Male , Multiple Organ Failure/therapy , Multiple Organ Failure/virology , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Retrospective Studies , SARS-CoV-2 , Treatment Outcome
12.
Biol Res Nurs ; 23(2): 258-269, 2021 04.
Article in English | MEDLINE | ID: covidwho-733072

ABSTRACT

At present, COVID-19 is raging all over the world. Many comorbidities, such as diabetes mellitus (OR = 2.67, 95% CI = 1.91-3.74) and hypertension (OR = 2.3, 95% CI = 1.76-3.00), have been shown to worsen the patient's condition. However, whether cardio-cerebrovascular disease will affect COVID-19 remains unclear. In this meta-analysis, we collected studies from PubMed, Wed of Science and CNKI (Chinese) to July 25, which reported COVID-19 patients with and without cardio-cerebrovascular disease as well as their severity and mortality. The random-effect model meta-analysis was used to analyze them and get overall odds ratios (OR) with 95% CIs. Funnel plots and the Begg's and Egger's test were used to assess publication bias. Thirty-one studies with 23,632 patients were finally included in the meta-analysis. The results showed an OR of 3.004 (95% CI = 2.097-4.303) for COVID-19 severity and an OR of 5.587 (95% CI = 2.810-11.112) for COVID-19 mortality. Compared with cardiovascular disease, the subgroup analysis indicated that cerebrovascular disease was more likely to increase the severity (OR = 3.400, 95% CI = 1.569-7.368) and mortality (OR = 23.477, 95% CI = 3.050-180.735) of COVID-19. Therefore, it can be inferred that cardio-cerebrovascular disease is associated with an increase in the risk of severe illness and death among COVID-19 patients. This meta-analysis showed that cardio-cerebrovascular disease has a significant relation with severe and death outcomes of COVID-19. Nurses should pay special attention to COVID-19 patients with the cardio-cerebrovascular disease.


Subject(s)
COVID-19/epidemiology , COVID-19/mortality , Cardiovascular Diseases/complications , Cardiovascular Diseases/mortality , Cause of Death , Cerebrovascular Disorders/complications , Cerebrovascular Disorders/mortality , Adult , Aged , Aged, 80 and over , Asian People , Cardiovascular Diseases/epidemiology , Cerebrovascular Disorders/epidemiology , Comorbidity , Female , Humans , Male , Middle Aged , Odds Ratio , SARS-CoV-2 , Severity of Illness Index
13.
Int J Infect Dis ; 96: 19-24, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-72509

ABSTRACT

The coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China and rapidly spread in other countries in December 2019. The infected patients presented with fever, respiratory symptoms, sometimes with digestive and other systemic manifestations, and some progressed with a severe acute respiratory syndrome or even death. Associated digestive symptoms were frequently observed in the patients, with an unknown significance and mechanism. ACE2, as the major known functional receptor of the 2019 novel coronavirus (2019-nCoV) attracted our attention. We collected the clinical data of the 2019-nCoV-infected patients from published studies and extracted the data about the incidence of gastrointestinal symptoms. Furthermore, we used online datasets to analyze ACE2 expression in different human organs, especially in the small intestine, to explore the relationship between ACE2 expression patterns and clinical symptoms. We found that diarrhea accounted for a notable proportion of COVID-19 patients, ranging from 8.0% to 12.9%. The results reveal that ACE2 mRNA and protein are highly expressed in the small intestinal enterocytes but not in the goblet cells or intestinal immune cells. High expression of ACE2 on the surface cells in the digestive tract may lead to gastrointestinal symptoms and inflammation susceptibility. Overall, digestive symptoms were common in the COVID-19 patients. ACE2 expression on surface cells of the small intestine may mediate the invasion and amplification of the virus and activation of gastrointestinal inflammation. It is a possible mechanism of digestive symptoms in the COVID-19 patients and explains the presence of the virus in patients' stool samples. The study also highlights the necessity of taking stool samples for suspected patients to help in early diagnosis and assessment of disease status.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Diarrhea/etiology , Enterocytes/enzymology , Gastrointestinal Diseases/etiology , Intestine, Small/enzymology , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral/complications , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2 , COVID-19 , Feces/virology , Female , Humans , Male , Middle Aged , Pandemics , Peptidyl-Dipeptidase A/genetics , SARS-CoV-2
14.
researchsquare; 2020.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-23260.v1

ABSTRACT

Objective To investigate the prevalence of sleep quality and mental disturbances of medical staff and identify the effects of region, epidemic stage, and demographic characteristics during the COVID-19 outbreak in China. Method Self-administered questionnaire were sent to health care workers (HCWs) in China from 30 Jan to 2 March, 2020. The Pittsburgh Sleep Quality Index, the Patient Health Questionare-9, the Generalized Anxiety Disorder-7 and the Impact of Event Scale were used to assess sleep quality, depression symptoms, anxiety symptoms and Post-traumatic stress disorder (PTSD) of HCWs, respectively. The influencing factors of psychological and sleep disturbances were identified by univariate analysis and multiple regression. Result The incidence of people getting depression, anxiety or PTSD symptoms were 11.6%,13.3%, 14.3%, respectively. HCWs in Hubei province experienced significantly poorer sleep quality (t=5.034, P<0.001). The predictors of sleep quality among HCWs were COVID-19 stage 2 (β=.135, p=.014) and 3 (β=.184, p=.001), female (β=.141, p=.003) and older age (β=.160, p=.001).Not working in Hubei province (β=-.264, P<0.001) showed to be a protective factor of sleep quality. The risk factors of depression symptoms were not working in Hubei province (OR=4.318, P<0.001), administrative and logistic staff and others (OR=3.538, p=.011), and higher PSQI score (OR=1.282, P<0.001). Having children (under-age: OR=.292, p=.001, grown-up: OR=.293, p=.042) was identified as a protective factor of having depression symptoms. Poor sleep quality showed to be the risk factor of anxiety and PTSD symptoms as well (both p<.001). Furthermore, administrative and logistic staff and others (OR=3.399, p=.006) were found to be the risk factor of PTSD symptoms among HCWs. Conclusion HCWs had poorer sleep quality on stage 2and 3 of the outbreak. HCWs in Hubei had poorer sleep quality but lighter depression condition. gender, age, occupation and status of having children were associated with sleep and mental health. Mental health programs should be considered for HCWs especially those with specific characteristics. Key words COVID-19, Depression, Anxiety, PTSD, Sleep quality, Health care workers


Subject(s)
Hallucinations , Depressive Disorder , COVID-19 , Stress Disorders, Traumatic , Sleep Wake Disorders , Stress Disorders, Post-Traumatic , Anxiety Disorders , Occupational Diseases
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