Relative COVID-19 Viral Persistence and Antibody Kinetics

A total of 15 RT-PCR confirmed COVID-19 patients were admitted to our hospital during the in-itial outbreak in Taiwan. The average time of virus clearance was delayed in seven patients, 24.14 ± 4.33 days compared to 10.25 ± 0.56 days post-symptom onset (PSO) in the other eight pa-tients. There was strong antibody response in patients with viral persistence at the pharynx, with peak values of serum antibody 677.2 ± 217.8 vs. 76.70 ± 32.11 in patients with delayed versus rapid virus clearance. The patients with delayed viral clearance had excessive antibodies of compromised quality in an early stage with the delay in peak virus neutralization efficacy, 34.14 ± 7.15 versus 12.50 ± 2.35 days PSO in patients with rapid virus clearance. Weak antibody re-sponse of patients with rapid viral clearance was also effective, with substantial and comparable neutralization efficacy, 35.70 ± 8.78 versus 41.37 ± 11.49 of patients with delayed virus clearance. Human Cytokine 48-Plex Screening of the serial sera samples revealed elevated concentrations of proinflammatory cytokines and chemokines in a deceased patient with delayed virus clear-ance and severe disease. The levels were comparatively less in the other two patients who suf-fered from severe disease but eventually survived.

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Interleukin-10 Modulation of Virus Clearance and Disease in Mice with Alphaviral Encephalomyelitis

Journal of Virology ◽

10.1128/jvi.01517-17 ◽

2017 ◽

Vol 92 (6) ◽

Cited By ~ 8

Author(s):

Nina M. Martin ◽

Diane E. Griffin

Keyword(s):

Weight Loss ◽

Virus Strain ◽

Th17 Cells ◽

Severe Disease ◽

Interleukin 10 ◽

Viral Clearance ◽

Th1 Cells ◽

Virus Clearance ◽

Virulent Virus ◽

Antiviral Antibody

ABSTRACTAlphaviruses are an important cause of mosquito-borne outbreaks of arthritis, rash, and encephalomyelitis. Previous studies in mice with a virulent strain (neuroadapted SINV [NSV]) of the alphavirus Sindbis virus (SINV) identified a role for Th17 cells and regulation by interleukin-10 (IL-10) in the pathogenesis of fatal encephalomyelitis (K. A. Kulcsar, V. K. Baxter, I. P. Greene, and D. E. Griffin, Proc Natl Acad Sci U S A 111:16053–16058, 2014,https://doi.org/10.1073/pnas.1418966111). To determine the role of virus virulence in generation of immune responses, we analyzed the modulatory effects of IL-10 on disease severity, virus clearance, and the CD4+T cell response to infection with a recombinant strain of SINV of intermediate virulence (TE12). The absence of IL-10 during TE12 infection led to longer morbidity, more weight loss, higher mortality, and slower viral clearance than in wild-type mice. More severe disease and impaired virus clearance in IL-10−/−mice were associated with more Th1 cells, fewer Th2 cells, innate lymphoid type 2 cells, regulatory cells, and B cells, and delayed production of antiviral antibody in the central nervous system (CNS) without an effect on Th17 cells. Therefore, IL-10 deficiency led to more severe disease in TE12-infected mice by increasing Th1 cells and by hampering development of the local B cell responses necessary for rapid production of antiviral antibody and virus clearance from the CNS. In addition, the shift from Th17 to Th1 responses with decreased virus virulence indicates that the effects of IL-10 deficiency on immunopathologic responses in the CNS during alphavirus infection are influenced by virus strain.IMPORTANCEAlphaviruses cause mosquito-borne outbreaks of encephalomyelitis, but determinants of outcome are incompletely understood. We analyzed the effects of the anti-inflammatory cytokine IL-10 on disease severity and virus clearance after infection with an alphavirus strain of intermediate virulence. The absence of IL-10 led to longer illness, more weight loss, more death, and slower viral clearance than in mice that produced IL-10. IL-10 influenced development of disease-causing T cells and entry into the brain of B cells producing antiviral antibody. The Th1 pathogenic cell subtype that developed in IL-10-deficient mice infected with a less virulent virus was distinct from the Th17 subtype that developed in response to a more virulent virus, indicating a role for virus strain in determining the immune response. Slow production of antibody in the nervous system led to delayed virus clearance. Therefore, both the virus strain and the host response to infection are important determinants of outcome.

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Cognitive Functioning and Other Discriminatory Variables in Anorexic Patients

Rorschachiana Journal of the International Society for the Rorschach ◽

10.1027/1192-5604.27.1.191 ◽

2005 ◽

Vol 27 (1) ◽

pp. 191-210 ◽

Cited By ~ 1

Author(s):

Carmen García-Alba

Keyword(s):

Cognitive Functioning ◽

Research Study ◽

Early Stage ◽

Developmental Period ◽

The Other ◽

Model Synthesis ◽

Consistent Function ◽

Current Article ◽

Rorschach Variables ◽

Underlying Pathology

This study is part of a larger research study (doctoral dissertation), in which a comparative study with adolescent samples is done: 50 anorexic restricting patients (ANP), 50 patients diagnosed with depression (DP) and 50 non patients (NP). The proposed objective is two-fold: 1) To try to clarify the existing relationship between Anorexia (AN) and Depression (D), investigated from diverse disciplines but without conclusive results. 2) To detect in the ANP personality different traits from those of other groups, which should, if possible, allow to detect them at an early stage for an adequate prognosis. The current article presents the Rorschach findings in relation to the cognitive functioning of the ANP. In them, the following has been detected: (1) An information processing similar to that of the other groups, even with a more complete (L ≤ .99), more complex (DQ+↑) and better discriminated (Zd↑) grasp of the stimulus; (2) Mediating processes very similar to those of the other groups, sharing with them the perceptive maladjustments (X–%↑) and an excessive individualism (Xu%↑); (3) A clearly differentiating ideation disorder. Definitely, the ANP use predominantly ideation (M↑), but their thought, usually well-adjusted (MQo↑), presents eventual operations of delusional type (MQnone↑). Above that, their thinking is marked by a great passivity (Mp↑), which makes them more vulnerable to accept ideas without criticizing them and it results in a very inefficient thinking, which spins around these concepts without finding solutions, entering into a sort of ruminating which is completely unproductive. The differences toward the obsessive pathology are established. The discriminant analysis conducted with all the Rorschach variables that resulted as significant throughout the research, provides quite a consistent function which discriminates the ANP: MQnone↑, Mp↑, FD↓, Ma↑, MQo↑, AdjD↑, Sum H↑, (H)↑. Based on this we can understand that these adolescents, being in a developmental period of big changes and disorientations in relation with their own image, confronted with life events, and possibly starting off with some biologic vulnerability: (1) Due to the alterations of their ideation, accept without criticism (Mp) irrational ideas dominating in our culture, in which slimness appears as the only model, synthesis of intelligence, beauty and success; remaining captured in this type of mental activity (MQnone), which they cannot escape nor criticize (Mp), despite they reason adequately on other topics (MQo); (2) Their alterations of self-perception [(H)] make them hide themselves in a fantasized image, which is the axis of their interests and the only thing that really matters to them; (3) The resources they have to decide on behaviors and to finish these deliberately (AdjD), and their scarce tendency to the introspection (FD) lead to their decision of not eating, based on distorted and passively accepted thinking, which has great power and thus, so difficult to modify. Finally, based on the Rorschach data obtained, the hypothesis of a personality disorder as underlying pathology is pointed out.

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The Application of UX Research in New Energy Vehicle Innovation

Conference Proceedings of the Academy for Design Innovation Management ◽

10.33114/adim.2017.58 ◽

2019 ◽

Vol 1 (1) ◽

Author(s):

Menghan TAO ◽

Ning XIAO ◽

Xingfu ZHAO ◽

Wenbin LIU

Keyword(s):

Early Stage ◽

Rapid Expansion ◽

The Other ◽

Innovative Product ◽

Stage Of Development ◽

New Energy ◽

New Energy Vehicle ◽

The One ◽

New Energy Vehicles ◽

Degree Of Innovation

New energy vehicles(NEV) as a new thing for sustainable development, in China, on the one hand has faced the rapid expansion of the market; the other hand, for the new NEV users, the current NEVs cannot keep up with the degree of innovation. This paper demonstrates the reasons for the existence of this systematic challenge, and puts forward the method of UX research which is different from the traditional petrol vehicles research in the early stage of development, which studies from the user's essence level, to form the innovative product programs which meet the needs of users and being real attractive.

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SARS-CoV-2-Laden Respiratory Aerosol Deposition in the Lung Alveolar-Interstitial Region Is a Potential Risk Factor for Severe Disease: A Modeling Study

Journal of Personalized Medicine ◽

10.3390/jpm11050431 ◽

2021 ◽

Vol 11 (5) ◽

pp. 431

Author(s):

Sabine Hofer ◽

Norbert Hofstätter ◽

Albert Duschl ◽

Martin Himly

Keyword(s):

Risk Factor ◽

Particle Deposition ◽

Early Stage ◽

Severe Disease ◽

Ambient Air ◽

Aerosol Deposition ◽

Pulmonary Involvement ◽

Mild Disease ◽

Disease Initiation

COVID-19, predominantly a mild disease, is associated with more severe clinical manifestation upon pulmonary involvement. Virion-laden aerosols and droplets target different anatomical sites for deposition. Compared to droplets, aerosols more readily advance into the peripheral lung. We performed in silico modeling to confirm the secondary pulmonary lobules as the primary site of disease initiation. By taking different anatomical aerosol origins into consideration and reflecting aerosols from exhalation maneuvers breathing and vocalization, the physicochemical properties of generated respiratory aerosol particles were defined upon conversion to droplet nuclei by evaporation at ambient air. To provide detailed, spatially-resolved information on particle deposition in the thoracic region of the lung, a top-down refinement approach was employed. Our study presents evidence for hot spots of aerosol deposition in lung generations beyond the terminal bronchiole, with a maximum in the secondary pulmonary lobules and a high preference to the lower lobes of both lungs. In vivo, initial chest CT anomalies, the ground glass opacities, resulting from partial alveolar filling and interstitial thickening in the secondary pulmonary lobules, are likewise localized in these lung generations, with the highest frequency in both lower lobes and in the early stage of disease. Hence, our results suggest a disease initiation right there upon inhalation of virion-laden respiratory aerosols, linking the aerosol transmission route to pathogenesis associated with higher disease burden and identifying aerosol transmission as a new independent risk factor for developing a pulmonary phase with a severe outcome.

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Berberine and Obatoclax Inhibit SARS-Cov-2 Replication in Primary Human Nasal Epithelial Cells In Vitro

Viruses ◽

10.3390/v13020282 ◽

2021 ◽

Vol 13 (2) ◽

pp. 282

Author(s):

Finny S. Varghese ◽

Esther van Woudenbergh ◽

Gijs J. Overheul ◽

Marc J. Eleveld ◽

Lisa Kurver ◽

...

Keyword(s):

Epithelial Cells ◽

Early Stage ◽

Antiviral Drugs ◽

Target Cells ◽

Nasal Epithelial Cells ◽

Cytokines And Chemokines ◽

Human Nasal Epithelial Cells ◽

Apoptotic Protein ◽

Air Liquid Interface

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a new human pathogen in late 2019 and it has infected over 100 million people in less than a year. There is a clear need for effective antiviral drugs to complement current preventive measures, including vaccines. In this study, we demonstrate that berberine and obatoclax, two broad-spectrum antiviral compounds, are effective against multiple isolates of SARS-CoV-2. Berberine, a plant-derived alkaloid, inhibited SARS-CoV-2 at low micromolar concentrations and obatoclax, which was originally developed as an anti-apoptotic protein antagonist, was effective at sub-micromolar concentrations. Time-of-addition studies indicated that berberine acts on the late stage of the viral life cycle. In agreement, berberine mildly affected viral RNA synthesis, but it strongly reduced infectious viral titers, leading to an increase in the particle-to-pfu ratio. In contrast, obatoclax acted at the early stage of the infection, which is in line with its activity to neutralize the acidic environment in endosomes. We assessed infection of primary human nasal epithelial cells that were cultured on an air-liquid interface and found that SARS-CoV-2 infection induced and repressed expression of specific sets of cytokines and chemokines. Moreover, both obatoclax and berberine inhibited SARS-CoV-2 replication in these primary target cells. We propose berberine and obatoclax as potential antiviral drugs against SARS-CoV-2 that could be considered for further efficacy testing.

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Cell Death in Coronavirus Infections: Uncovering Its Role during COVID-19

Cells ◽

10.3390/cells10071585 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1585

Author(s):

Annamaria Paolini ◽

Rebecca Borella ◽

Sara De Biasi ◽

Anita Neroni ◽

Marco Mattioli ◽

...

Keyword(s):

Cell Death ◽

Immune Cells ◽

Viral Infections ◽

Virus Entry ◽

Therapeutic Strategies ◽

The Other ◽

Cytokine Storm ◽

Cytokines And Chemokines ◽

Cell Death Mechanisms ◽

The One

Cell death mechanisms are crucial to maintain an appropriate environment for the functionality of healthy cells. However, during viral infections, dysregulation of these processes can be present and can participate in the pathogenetic mechanisms of the disease. In this review, we describe some features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and some immunopathogenic mechanisms characterizing the present coronavirus disease (COVID-19). Lymphopenia and monocytopenia are important contributors to COVID-19 immunopathogenesis. The fine mechanisms underlying these phenomena are still unknown, and several hypotheses have been raised, some of which assign a role to cell death as far as the reduction of specific types of immune cells is concerned. Thus, we discuss three major pathways such as apoptosis, necroptosis, and pyroptosis, and suggest that all of them likely occur simultaneously in COVID-19 patients. We describe that SARS-CoV-2 can have both a direct and an indirect role in inducing cell death. Indeed, on the one hand, cell death can be caused by the virus entry into cells, on the other, the excessive concentration of cytokines and chemokines, a process that is known as a COVID-19-related cytokine storm, exerts deleterious effects on circulating immune cells. However, the overall knowledge of these mechanisms is still scarce and further studies are needed to delineate new therapeutic strategies.

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Direct Nucleation of Crystalline SiGe on Substrates by Reactive Thermal CVD with Si2H6 and GeF4

MRS Proceedings ◽

10.1557/proc-467-349 ◽

1997 ◽

Vol 467 ◽

Cited By ~ 1

Author(s):

Fumio Yoshizawa ◽

Kunihiro Shiota ◽

Daisuke Inoue ◽

Jun-ichi Hanna

Keyword(s):

Growth Rate ◽

Gas Phase ◽

Heterogeneous Nucleation ◽

Homogeneous Nucleation ◽

Film Growth ◽

Early Stage ◽

Gaseous Mixture ◽

The Other ◽

Thermal Cvd ◽

Initial Deposition

ABSTRACTPolycrystalline SiGe (poly-SiGe) film growth by reactive thermal CVD with a gaseous mixture of Si2H6 and GeF4 was investigated on various substrates such as Al,Cr, Pt, Si, ITO, ZnO and thermally grown SiO2.In Ge-rich film growth, SEM observation in the early stage of the film growth revealed that direct nucleation of crystallites took place on the substrates. The nucleation was governed by two different mechanisms: one was a heterogeneous nucleation on the surface and the other was a homogeneous nucleation in the gas phase. In the former case, the selective nucleation was observed at temperatures lower than 400°C on metal substrates and Si, where the activation of adsorbed GeF4 on the surface played a major role for the nuclei formation, leading to the selective film growth.On the other hand, the direct nucleation did not always take place in Si-rich film growth irrespective of the substrates and depended on the growth rate. In a growth rate of 3.6nm/min, the high crystallinity of poly-Si0.95Ge0.05in a 220nm-thick film was achieved at 450°C due to the no initial deposition of amorphous tissue on SiO2 substrates.

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Recovery of subjective visual horizontal after unilateral vestibular deafferentation by intratympanic instillation of gentamicin

Journal of Vestibular Research ◽

10.3233/ves-2006-161-207 ◽

2006 ◽

Vol 16 (1-2) ◽

pp. 69-73 ◽

Cited By ~ 4

Author(s):

Yoshinari Takai ◽

Toshihisa Murofushi ◽

Munetaka Ushio ◽

Shinichi Iwasaki

Keyword(s):

Healthy Subjects ◽

Time Course ◽

Early Stage ◽

Ccd Camera ◽

The Other ◽

Spontaneous Nystagmus ◽

Vestibular Evoked Myogenic Potentials ◽

Normal Range ◽

Intratympanic Gentamicin ◽

Unilateral Vestibular Deafferentation

The time course of the recovery of subjective visual horizontal (SVH) after unilateral vestibular deafferentation by intratympanic instillation of gentamicin was studied. Six patients who underwent intratympanic gentamicin instillation therapy for Meniere's disease (1 man and 5 women, 32 to 69 years of age) were enrolled in this study. For comparison, SVH in 23 healthy subjects (12 men and 11 woman, 23 to 48 years of age) was also measured. The mean ± SD of SVH in healthy subjects was 0.0 ± 1.1 deg. All of the 6 patients showed significantly deviated SVH toward the injected side-down at the early stage after the therapy. Although one patient showed recovery of SVH to the normal range 25 days after the injection, the other patients required more time for recovery. Three patients did not show recovery to the normal range after 1 year. On the other hand, spontaneous nystagmus observed using an infrared CCD camera in total dark disappeared after 35 days (median). Patients who had normal vestibular evoked myogenic potentials before the therapy showed a tendency of delay of recovery of SVH. The reasons why the recovery of SVH took longer than the disappearance of spontaneous nystagmus are discussed in this report.

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In situ cytokine gene expression in early stage of virulent Newcastle disease in chickens

Veterinary Pathology ◽

10.1177/03009858211045945 ◽

2021 ◽

pp. 030098582110459

Author(s):

Corrie Brown ◽

Jian Zhang ◽

Mary Pantin-Jackwood ◽

Kiril Dimitrov ◽

Helena Lage Ferreira ◽

...

Keyword(s):

B Cells ◽

Newcastle Disease ◽

Early Stage ◽

Severe Disease ◽

Cytokine Gene Expression ◽

Lymphoid Tissues ◽

Tnf Α ◽

Virulent Newcastle Disease Virus ◽

Ifn Γ

Selected lymphoid and reproductive tissues were examined from groups of 3-week-old chickens and 62-week-old hens that were inoculated choanally and conjunctivally with 106 EID50 of a virulent Newcastle disease virus (NDV) isolate from the California 2018–2020 outbreak, and euthanized at 1, 2, and 3 days postinfection. In the 3-week-old chickens, immunohistochemistry for NDV and for T and B cell lymphocytes, as well as in situ hybridization for IL-1β, IL-6, IFN-γ, and TNF-α revealed extensive expression of IL-1β and IL-6 in lymphoid tissues, often coinciding with NDV antigen. IFN-γ was only expressed infrequently in the same lymphoid tissues, and TNF-α was rarely expressed. T-cell populations initially expanded but by day 3 their numbers were below control levels. B cells underwent a similar expansion but remained elevated in some tissues, notably spleen, cecal tonsils, and cloacal bursa. Cytokine expression in the 62-week-old hens was overall lower than in the 3-week-old birds, and there was more prolonged infiltration of both T and B cells in the older birds. The strong pro-inflammatory cytokine response in young chickens is proposed as the reason for more severe disease.

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MÓZGOWE PODŁOŻE ROZWOJU MOWY W AUTYZMIE

Poradnik Językowy ◽

10.33896/porj.2021.6.3 ◽

2021 ◽

pp. 39-51

Author(s):

Krystyna Rymarczyk

Keyword(s):

Early Stage ◽

Autism Spectrum ◽

Speech Development ◽

The Other ◽

Arcuate Fasciculus ◽

Foetal Life ◽

Behavioural Research ◽

Speech Development Disorders ◽

Structure And Activity ◽

Atypical Brain Development

Although in a majority of cases, autistic children face difficulties communicating verbally, the valid diagnostic classifi cations do not identify them as the main symptoms of the disorder. The adoption of such a position has been supported by results of (mainly behavioural) research, which imply that language and speech development in the autism spectrum disorder (ASD) is extremely variable and individually diversifi ed and the observed delay of its development is not unique to autism. On the other hand, the research conducted by means of neuroimaging methods shows that an atypical structure and activity of Broca’s and Wernicke’s areas, which are important for language processes, exist in the ASD. A weak structural and functional connectivity in the arcuate fasciculus, which connects these structures, has also been discovered. It is assumed that the changes arise from neurodevelopmental irregularities occurring at an early stage of foetal life and their causes are probably genetic. This study characterises speech development disorders and atypical brain development in autism referring to results of both behavioural and neuroimaging research.

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