Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 206
Filter
Add filters

Year range
1.
Clin Rev Allergy Immunol ; 2022 Jan 18.
Article in English | MEDLINE | ID: covidwho-1636692

ABSTRACT

Abnormal immunological indicators associated with disease severity and mortality in patients with COVID-19 have been reported in several observational studies. However, there are marked heterogeneities in patient characteristics and research methodologies in these studies. We aimed to provide an updated synthesis of the association between immune-related indicators and COVID-19 prognosis. We conducted an electronic search of PubMed, Scopus, Ovid, Willey, Web of Science, Cochrane library, and CNKI for studies reporting immunological and/or immune-related parameters, including hematological, inflammatory, coagulation, and biochemical variables, tested on hospital admission of COVID-19 patients with different severities and outcomes. A total of 145 studies were included in the current meta-analysis, with 26 immunological, 11 hematological, 5 inflammatory, 4 coagulation, and 10 biochemical variables reported. Of them, levels of cytokines, including IL-1ß, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, IFN-γ, IgA, IgG, and CD4+ T/CD8+ T cell ratio, WBC, neutrophil, platelet, ESR, CRP, ferritin, SAA, D-dimer, FIB, and LDH were significantly increased in severely ill patients or non-survivors. Moreover, non-severely ill patients or survivors presented significantly higher counts of lymphocytes, monocytes, lymphocyte/monocyte ratio, eosinophils, CD3+ T,CD4+T and CD8+T cells, B cells, and NK cells. The currently updated meta-analysis primarily identified a hypercytokinemia profile with the severity and mortality of COVID-19 containing IL-1ß, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, and IFN-γ. Impaired innate and adaptive immune responses, reflected by decreased eosinophils, lymphocytes, monocytes, B cells, NK cells, T cells, and their subtype CD4+ and CD8+ T cells, and augmented inflammation, coagulation dysfunction, and nonpulmonary organ injury, were marked features of patients with poor prognosis. Therefore, parameters of immune response dysfunction combined with inflammatory, coagulated, or nonpulmonary organ injury indicators may be more sensitive to predict severe patients and those non-survivors.

2.
Vaccines (Basel) ; 10(1)2022 Jan 17.
Article in English | MEDLINE | ID: covidwho-1625891

ABSTRACT

Patients with diabetes are more susceptible to severe acute respiratory syndrome-associated coronavirus (SARS-CoV)-2 infection, but vaccine hesitancy is a problem in this population. We investigated the prevalence of SARS-CoV-2 vaccine hesitancy among diabetes patients in China through a cross-sectional survey from April and August 2021 using a questionnaire administered to patients at two hospitals affiliated with Changzhi Medical College (Shanxi, China). The health belief model (HBM) is used examining factors influencing vaccine hesitancy. After adjusting for potential confounders, a multivariate logistic regression model was used to analyze correlations between vaccine hesitancy and associated factors. Of the 483 participants, 56.4% (273/483) had vaccine hesitancy, including 58.2% (159/273) who were unsure of being vaccinated and 41.8% (114/273) who were unwilling. Although patients considered SARS-CoV-2 infection to be serious (adjusted odds ratio [aOR] = 3.90, 95% confidence interval [CI]: 2.36-6.42; p < 0.001), they had concerns about vaccine safety (aOR = 3.05, 95% CI: 1.89-4.91; p < 0.001). Relatives' vaccination status did not influence participants' willingness to be vaccinated (aOR = 2.43, 95% CI: 1.39-4.25; p < 0.001). Disagreement with physicians' view that vaccination can reduce SARS-CoV-2 infection risk was independently correlated with vaccine hesitancy (aOR = 2.25, 95% CI: 1.28-3.95; p < 0.001). Diabetes patients in China need to be educated on SARS-CoV-2 vaccine safety and protective effects to increase the vaccination rate in this population.

4.
Gut ; 2021 Nov 26.
Article in English | MEDLINE | ID: covidwho-1622066

ABSTRACT

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

6.
J Med Chem ; 2022 Jan 10.
Article in English | MEDLINE | ID: covidwho-1616927

ABSTRACT

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the most common complications in COVID-19. Elastase has been recognized as an important target to prevent ALI/ARDS in the patient of COVID-19. Cyclotheonellazole A (CTL-A) is a natural macrocyclic peptide reported to be a potent elastase inhibitor. Herein, we completed the first total synthesis of CTL-A in 24 linear steps. The key reactions include three-component MAC reactions and two late-stage oxidations. We also provided seven CTL-A analogues and elucidated preliminary structure-activity relationships. The in vivo ALI mouse model further suggested that CTL-A alleviated acute lung injury with reductions in lung edema and pathological deterioration, which is better than sivelestat, one approved elastase inhibitor. The activity of CTL-A against elastase, along with its cellular safety and well-established synthetic route, warrants further investigation of CTL-A as a candidate against COVID-19 pathogeneses.

7.
Viruses ; 14(1)2022 Jan 04.
Article in English | MEDLINE | ID: covidwho-1614003

ABSTRACT

The coronavirus disease 2019 (COVID-19) has spread globally and variants continue to emerge, with children are accounting for a growing share of COVID-19 cases. However, the establishment of immune memory and the long-term health consequences in asymptomatic or mildly symptomatic children after severe acute respiratory syndrome coronavirus 2 infection are not fully understood. We collected clinical data and whole blood samples from discharged children for 6-8 months after symptom onset among 0-to-14-year-old children. Representative inflammation signs returned to normal in all age ranges. The infants and young children (0-4 years old) had lung lesions that persisted for 6-8 months and were less responsive for antigen-specific IgG secretion. In the 5-to-14-year-old group, lung imaging abnormalities gradually recovered, and the IgG-specific antibody response was strongest. In addition, we found a robust IgM+ memory B cell response in all age. Memory T cells specific for the spike or nucleocapsid protein were generated, with no significant difference in IFN-γ response among all ages. Our study highlights that although lung lesions caused by COVID-19 can last for at least 6-8 months in infants and young children, most children have detectable residual neutralizing antibodies and specific cellular immune responses at this stage.

8.
BMC Psychiatry ; 21(1): 530, 2021 10 27.
Article in English | MEDLINE | ID: covidwho-1594206

ABSTRACT

BACKGROUND: An increasing number of undergraduate students in China have been reported to have psychological problems. In response to the COVID-19 pandemic, a series of preventive and control measures were implemented, which undoubtedly worsened their psychological health. Coping style and social support were probably important factors that affected the psychological well-being of undergraduate students during the pandemic. This study aimed to explore the effects of coping style and perceived social support on the psychological well-being of college students and relevant risk factors. METHODS: This cross-sectional study was performed in February and March of 2020 by distributing an online questionnaire among undergraduate students from seven geographical regions across China. The questionnaire included sociodemographic information; the 21-item Depression, Anxiety and Stress Scale (DASS-21); the Perceived Social Support Scale (PSSS); and the Simplified Coping Style Questionnaire (SCSQ). For the analyses, t-tests, one-way analysis of variance (ANOVA), the Kruskal-Wallis test and multiple linear regression were utilized. The level of significance was set at P < 0.05. RESULTS: Among 3113 college students, the rates of anxiety, depression and stress symptoms were 13.3, 15.4 and 6.8%, respectively. Increased rates of current smoking and drinking (5.5 and 25.2%, respectively) among undergraduates were identified. The results indicated that the PSSS subscales and SCSQ subscales were significantly associated with DASS-21 scores (P < 0.001). Multiple linear regression analysis showed that active coping style and family support were protective factors while passive coping style could aggravate psychological problems among participants (P < 0.001). CONCLUSIONS: A remarkable number of college students adopted passive coping strategies to cope with negative feelings, such as smoking and drinking, which were detrimental to their mental health. In contrast, active coping strategies helped improve their psychological well-being. Moreover, family support was particularly important for maintaining their mental health and ameliorating mental health challenges in this major health crisis. Consequently, suitable psychointervention, routine screening for risk behaviors, and provision of further social support are needed for undergraduate students in the COVID-19 pandemic or other emergency public health events.


Subject(s)
COVID-19 , Pandemics , Adaptation, Psychological , Anxiety/epidemiology , China/epidemiology , Cross-Sectional Studies , Depression/epidemiology , Humans , Mental Health , SARS-CoV-2 , Social Support , Students , Surveys and Questionnaires
9.
Environ Sci Technol ; 56(2): 862-873, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1599640

ABSTRACT

Since the COVID-19 pandemic is expected to become endemic, quantification of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in ambient waters is critical for environmental surveillance and for early detection of outbreaks. Herein, we report the development of a membrane-based in-gel loop-mediated isothermal amplification (mgLAMP) system that is designed for the rapid point-of-use quantification of SARS-CoV-2 particles in environmental waters. The mgLAMP system integrates the viral concentration, in-assay viral lysis, and on-membrane hydrogel-based RT-LAMP quantification using enhanced fluorescence detection with a target-specific probe. With a sample-to-result time of less than 1 h, mgLAMP successfully detected SARS-CoV-2 below 0.96 copies/mL in Milli-Q water. In surface water, the lowest detected SARS-CoV-2 concentration was 93 copies/mL for mgLAMP, while the reverse transcription quantitative polymerase chain reaction (RT-qPCR) with optimal pretreatment was inhibited at 930 copies/mL. A 3D-printed portable device is designed to integrate heated incubation and fluorescence illumination for the simultaneous analysis of nine mgLAMP assays. Smartphone-based imaging and machine learning-based image processing are used for the interpretation of results. In this report, we demonstrate that mgLAMP is a promising method for large-scale environmental surveillance of SARS-CoV-2 without the need for specialized equipment, highly trained personnel, and labor-intensive procedures.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Molecular Diagnostic Techniques , Nucleic Acid Amplification Techniques , Pandemics , RNA, Viral , Sensitivity and Specificity
10.
Inquiry ; 58: 469580211059953, 2021.
Article in English | MEDLINE | ID: covidwho-1598094

ABSTRACT

BACKGROUND: College students are vulnerable and may experience high stress due to COVID-19, especially girls. This study aims to identify posttraumatic stress disorder (PTSD) and related factors among the target population during the initial phases of the COVID-19 pandemic. METHODS: In the initial phase of COVID-19 epidemic (February 23 to March 5, 2020), 2205 female college students from six provinces in mainland China were enrolled in this study and completed the online survey about the cognitive status of COVID-19, including the Impact of Event Scale-6, the Multidimensional Perceived Social Support Scale and a self-developed 10-item Perceived threat scale. Univariate and multivariate logistic regression were performed using SPSS software to explore the determinants of PTSD symptoms. RESULTS: PTSD symptoms were prevalent in female college students, and 34.20% met the cut-off for PTSD. Self-reported fair or poor health (AOR = 1.78, 95% CI: 1.22-2.59), high concern about COVID-19 (AOR = 1.66, 95% CI: 1.35-2.03), beliefs that "COVID-19 can cause a global outbreak" (AOR = 1.26, 95% CI: 1.02-1.56), the perception of "risk of infection" (AOR = 2.46, 95% CI: 2.16-2.81), beliefs that "closed management" and "COVID-19 as a public health emergency of international concern" would have an impact, and the fear of "impact on life planning" were all positively associated with PTSD (AOR = 1.37, 1.22, and 1.29, respectively); however, perceived social support from family (AOR = 0.81, 95% CI: 0.70-0.93) was negatively associated with PTSD. Among the significant variables at the bivariate level, multivariate logistic regression revealed that the greatest protector for PTSD was the high knowledge score (AOR = 0.73, 95% CI: 0.60-0.90), while had confirmed cases among relatives and friends (AOR = 7.70, 95% CI: 1.28-46.25) was the strongest predictor of PTSD. CONCLUSIONS: In summary, PTSD symptoms were prevalent among female college students in China during the COVID-19 epidemic. Targeting vulnerable populations to improve their knowledge about COVID-19 and create an atmosphere of social support would be beneficial. Moreover, the joint efforts from family, school administrators, and policymakers are essential to improve the mental health of the female students during the COVID-19 epidemic.


Subject(s)
COVID-19 , Stress Disorders, Post-Traumatic , Anxiety , China/epidemiology , Cross-Sectional Studies , Depression , Female , Humans , Pandemics , Prevalence , SARS-CoV-2 , Stress Disorders, Post-Traumatic/epidemiology , Students , Surveys and Questionnaires
11.
Lancet ; 2021 Nov 11.
Article in English | MEDLINE | ID: covidwho-1586226
12.
Sports Med Health Sci ; 2021 Dec 25.
Article in English | MEDLINE | ID: covidwho-1586495

ABSTRACT

Under the condition of normalized epidemic, how athletes train and compete well has been in the spotlight. This article reported the symptom, hospitalization and training situation of seven confirmed cases of coronavirus-disease-2019 (COVID-19) among Chinese national teams. Moreover, the paper summarized the experience of Chinese national teams in terms of epidemic prevention and control, treatment of infection, and safe return to play. Through a scientific combination of medication and non-medical treatment, seven athletes were all discharged from the hospital. These discharged athletes underwent strict isolation and scientific training before returning to sports teams. Before returning to play, continuous monitoring of physical and mental condition was required. All seven athletes returned to play safely and performed excellently. As for hosting large-scale sporting events, the entire enclosed-loop management from immigration to competition was proposed in this paper. This study could serve as a standard of epidemic prevention and control, treatment for infection and safe return to play during competition and training around the world.

13.
Front Microbiol ; 12: 805223, 2021.
Article in English | MEDLINE | ID: covidwho-1581269

ABSTRACT

Deubiquitylating enzymes (DUBs) are proteases that crack the ubiquitin code from ubiquitylated substrates to reverse the fate of substrate proteins. Recently, DUBs have been found to mediate various cellular biological functions, including antiviral innate immune response mediated by pattern-recognition receptors (PRRs) and NLR Family pyrin domain containing 3 (NLRP3) inflammasomes. So far, many DUBs have been identified to exert a distinct function in fine-tuning antiviral innate immunity and are utilized by viruses for immune evasion. Here, the recent advances in the regulation of antiviral responses by DUBs are reviewed. We also discussed the DUBs-mediated interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and antiviral innate immunity. The understanding of the mechanisms on antiviral innate immunity regulated by DUBs may provide therapeutic opportunities for viral infection.

14.
Vaccines (Basel) ; 10(1)2021 Dec 23.
Article in English | MEDLINE | ID: covidwho-1580361

ABSTRACT

COVID-19 seroprevalence changes over time, with infection, vaccination, and waning immunity. Seroprevalence estimates are needed to determine when increased COVID-19 vaccination coverage is needed, and when booster doses should be considered, to reduce the spread and disease severity of COVID-19 infection. We use an age-structured model including infection, vaccination and waning immunity to estimate the distribution of immunity to COVID-19 in the Canadian population. This is the first mathematical model to do so. We estimate that 60-80% of the Canadian population has some immunity to COVID-19 by late Summer 2021, depending on specific characteristics of the vaccine and the waning rate of immunity. Models results indicate that increased vaccination uptake in age groups 12-29, and booster doses in age group 50+ are needed to reduce the severity COVID-19 Fall 2021 resurgence.

15.
Brain Sci ; 11(12)2021 Dec 09.
Article in English | MEDLINE | ID: covidwho-1572367

ABSTRACT

Nasal breathing is a dynamic cortical organizer involved in various behaviors and states, such as locomotion, exploration, memory, emotion, introspection. However, the effect of sensory deprivation of nasal respiratory breath (NRD) on behavior remain poorly understood. Herein, general locomotor activity, emotion, learning and memory, social interaction, and mechanical pain were evaluated using a zinc sulfate nasal irrigation induced nasal respiratory sensory deprivation animal model (ZnSO4-induced mouse model). In the open field test, the elevated O-maze test, and forced swim test, NRD mice exhibited depressive and anxiety-like behaviors. In memory-associated tests, NRD mice showed cognitive impairments in the hippocampal-dependent memory (Y maze, object recognition task, and contextual fear conditioning (CFC)) and amygdala-dependent memory (the tone-cued fear conditioning test (TFC)). Surprisingly, NRD mice did not display deficits in the acquisition of conditional fear in both CFC and TFC tests. Still, they showed significant memory retrieval impairment in TFC and enhanced memory retrieval in CFC. At the same time, in the social novelty test using a three-chamber setting, NRD mice showed impaired social and social novelty behavior. Lastly, in the von Frey filaments test, we found that the pain sensitivity of NRD mice was reduced. In conclusion, this NRD mouse model showed a variety of behavioral phenotypic changes, which could offer an important insight into the behavioral impacts of patients with anosmia or those with an impaired olfactory bulb (OB) (e.g., in COVID-19, Alzheimer's disease, Parkinson's disease, etc.).

16.
The American Review of Public Administration ; : 02750740211059534, 2021.
Article in English | Sage | ID: covidwho-1556975

ABSTRACT

COVID-19 has created long-lasting yet unprecedented challenges worldwide. In addition to scientific efforts, political efforts and public administration are also crucial to contain the disease. Therefore, understanding how multi-level governance systems respond to this public health crisis is vital to combat COVID-19. This study focuses on China and applies social network analysis to illustrate interactive governance between and within levels and functions of government, confirming and extending the existing Type I and Type II definition of multi-level governance theory. We characterize four interaction patterns?vertical, inter-functional, intra-functional, and hybrid?with the dominant pattern differing across governmental functions and evolving as the pandemic progressed. Empirical results reveal that financial departments of different levels of government interact through the vertical pattern. At the same time, intra-functional interaction also exists in provincial financial departments. The supervision departments typically adopt the inter-functional pattern at all levels. At the cross-level and cross-function aspects, the hybrid interaction pattern prevails in the medical function and plays a fair part in the security, welfare, and economic function. This study is one of the first to summarize the interaction patterns in a multi-level setting, providing practical implications for which pattern should be applied to which governmental levels/functions under what pandemic condition.

17.
Preprint in English | EuropePMC | ID: ppcovidwho-296393

ABSTRACT

Fully effective vaccines for viruses such as Influenza and SARS-CoV-2 must elicit a diverse repertoire of antibodies against multiple drifted virus strains. However, how to achieve a diverse response has no general solution except to combine multiple strains, which risks diluting the response for all strains included. Here, we describe the synthesis of a universal, toll-like receptor 7 agonist (TLR7)-nanoparticle adjuvant, TLR7-NP, constructed from TLR7 agonist-initiated ring-opening polymerization of lactide and self-assembly with poly(ethylene glycol)- b -poly(lactic-co-glycolic acid). When mixed with Alum-adsorbed antigens, this TLR7-NP adjuvant elicited cross-reactive antibodies for both dominant and subdominant epitopes, as well as antigen-specific CD8 + T cell responses. TLR7-NPs adjuvanted influenza subunit vaccine successfully protected mice from heterologous viral challenge. TLR7-NPs also enhanced the antibody response to a SARS-CoV-2 subunit vaccine against multiple variants and revealed the mobilization of a virus-like response. We further demonstrate enhanced antigen-specific responses in human tonsil organoids with this novel adjuvant.

18.
Front Med (Lausanne) ; 8: 729138, 2021.
Article in English | MEDLINE | ID: covidwho-1556289

ABSTRACT

Coronaviruses (CoV) cause respiratory and intestinal infections. We conducted this bibliometric analysis and systematical review to explore the CoV-related research trends from before COVID-19. We systematically searched the Ovid MEDLINE, Ovid Embase, and Web of Science (WOS) databases for published bibliometric analyses of CoV from database inception to January 24, 2021. The WOS Collection was searched from inception to January 31, 2020, to acquire the CoV-related publications before COVID-19. One-Way ANOVA and Bonferroni multiple-comparison tests were used to compare differences. Visualization mapping and keyword cluster graphs were made to illustrate the research topics and hotpots. We included 14,141 CoV-related publications for the bibliometric analysis and 16 (12 articles) CoV-related bibliometric analyses for the systematic review. Both the systematic review and bibliometric analysis showed (1) the number of publications showed two steep upward trajectories in 2003-2004 and in 2012-2014; (2) the research hotpots mainly focused on the mechanism, pathology, epidemiology, clinical diagnosis, and treatment of the coronavirus in MERS-CoV and SARS-Cov; (3) the USA, and China; the University of Hong Kong; and Yuen KY, came from the University of Hong Kong contributed most; (4) the Journal of Virology had the largest number of CoV related studies. More studies should focus on prevention, diagnosis, and treatment in the future.

19.
Front Psychiatry ; 12: 596428, 2021.
Article in English | MEDLINE | ID: covidwho-1555689

ABSTRACT

Purpose: Understand the effects of the COVID-19 pandemic on depression in intensive care unit (ICU) nurses, analyze high-risk factors, and propose appropriate measures to maintain physical and mental health. Methods: A total of 78 nurses in ICU of Beijing Ditan Hospital affiliated with Capital Medical University (Beijing area, COVID-19 patient designated hospital) were investigated with self-rating depression scale (SDS). The Cronbach'sαcoefficient was 0.874, the content validity was 0.853, and the internal consistency was good. General information for the questionnaire: gender, marriage, education, age, title, length of service, ICU years of service, COVID-19 pandemic training, concerns about the COVID-19 pandemic, and current health status. Results: According to the SDS scale score, ICU nurses had a total depression score of 51.36 ± 11.667, and the prevalence rate of depression was 44.9% (35/78). Multi-line regression analysis shows that stress perception, work experience in critical diseases, education and other total scores are risk factors for the occurrence of depression. Conclusion: Work experience in critical illness (ß = 9.930, P < 0.001) had a positive predictive effect on the total score of depression, while stress perception (ß = -0.884, P < 0.001) and education (ß = -6.061, P < 0.001) had a negative predictive effect on the total score of depression, and explained 52.7% variation. These findings point to the need for interventions to address psychological distress and provide the necessary support.

20.
Front Microbiol ; 12: 789374, 2021.
Article in English | MEDLINE | ID: covidwho-1551520

ABSTRACT

SARS-CoV-2 has caused a global health disaster with millions of death worldwide, and the substantial proportion of asymptomatic carriers poses a huge threat to public health. The long-term antibody responses and neutralization activity during natural asymptomatic SARS-CoV-2 infection are unknown. In this study, we used enzyme-linked immunosorbent assays (ELISA) and neutralization assay with purified SARS-CoV-2S and N proteins to study the antibody responses of 156 individuals with natural asymptomatic infection. We found robust antibody responses to SARS-CoV-2 in 156 patients from 6 to 12 months. Although the antibody responses gradually decreased, S-IgG was more stable than N-IgG. S-IgG was still detected in 79% of naturally infected individuals after 12 months of infection. Moderate to potent neutralization activities were also observed in 98.74% of patients 6 months after infection. However, this proportion decreased at 8-month (46.15%) and 10-month (39.11%) after infection, respectively. Only 23.72% of patients displayed potent neutralization activity at 12 months. This study strongly supports the long-term presence of antibodies against SARS-CoV-2 in individuals with natural asymptomatic infection, although the magnitude of the antibody responses started to cripple 6 months after infection.

SELECTION OF CITATIONS
SEARCH DETAIL
...