scholarly journals COVID-19: Multiorgan Dissemination of SARS-CoV-2 Is Driven by Pulmonary Factors

Viruses ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 39
Author(s):  
Akmaljon Odilov ◽  
Alexey Volkov ◽  
Adhamjon Abdullaev ◽  
Tatiana Gasanova ◽  
Tatiana Lipina ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Organ Failure ◽  
Diffuse Alveolar Damage ◽  
Fatal Outcome ◽  
Risk Of Death ◽  
Multi Organ Failure ◽  
Common Causes ◽  
The Common ◽  
Spleen And Lymph Nodes ◽  
High Level

Multi-organ failure is one of the common causes of fatal outcome in COVID-19 patients. However, the pathogenetic association of the SARS-CoV-2 viral load (VL) level with fatal dysfunctions of the lungs, liver, kidneys, heart, spleen and brain, as well as with the risk of death in COVID-19 patients remains poorly understood. SARS-CoV-2 VL in the lungs, heart, liver, kidneys, brain, spleen and lymph nodes have been measured by RT qPCR using the following formula: NSARS-CoV−2/NABL1 × 100. Dissemination of SARS-CoV-2 in 30.5% of cases was mono-organ, and in 63.9% of cases, it was multi-organ. The average SARS-CoV-2 VL in the exudative phase of diffuse alveolar damage (DAD) was 60 times higher than in the proliferative phase. The SARS-CoV-2 VL in the lungs ranged from 0 to 250,281 copies. The “pulmonary factors” of SARS-CoV-2 multi-organ dissemination are the high level of SARS-CoV-2 VL (≥4909) and the exudative phase of DAD. The frequency of SARS-CoV-2 dissemination to lymph nodes was 86.9%, heart–56.5%, spleen–52.2%, liver–47.8%, kidney–26%, and brain–13%. We found no link between the SARS-CoV-2 VL level in the liver, kidneys, and heart and the serum level of CPK, LDH, ALP, ALT, AST and Cr of COVID-19 patients. Isolated detection of SARS-CoV-2 RNA in the myocardium of COVID-19 patients who died from heart failure is possible. The pathogenesis of COVID-19-associated multi-organ failure requires further research in a larger cohort of patients.

P6387Post-cardiac arrest syndrome (PCAS)-feasibility study. Impact of multi-organ failure on early prognosis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Czerwinska ◽  
J G Grand ◽  
G T Tavazzi ◽  
J S R Sans-Rosello ◽  
A W Wood ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Respiratory Failure ◽  
Organ Failure ◽  
Feasibility Study ◽  
Sofa Score ◽  
Predictive Value ◽  
Early Mortality ◽  
Risk Of Death ◽  
Multi Organ Failure ◽  
Post Cardiac Arrest Syndrome

Abstract Out-of hospital cardiac arrest (OHCA) of cardiac etiology is a leading cause of death in developed countries. Despite the improvement in rate of successfully resuscitated OHCA patients, their survival to discharge is generally poor. Multi-organ failure (MOF) due to post-cardiac arrest syndrome seems to be important in early prognostication after OHCA. Yet, the profile of organ failure and its prognostic value on early mortality after OHCA is unknown. The aim of the study was to perform a holistic analysis of MOF and its impact on early prognosis in patients after OHCA due to cardiac causes. Methods Post-cardiac arrest syndrome (PCAS)–feasibility study, was a multicenter, international project approved and endorsed by the Acute Cardiovascular Care Association (ACCA) lead by doctors associated with the Young ACC Community (YAC3). Inclusion criteria were: OHCA primarily due to cardiac causes, admission to ACCA center after ROSC. Criterion for feasibility was to recruit 100 pts within 12 months from the beginning of the study. Organ function parameters were assessed on admission, than every 24h, until 72h of stay. MOF was defined according to Sequential Organ Failure Assessment (SOFA) score & modified ADRS Berlin definition. Follow-up was 30-days. Primary end points were in-hospital and 30-day mortality. For statistical analysis Fisher exact test, non-parametric Mann–Whitney U test, and logistic regression were used. All p-values <0.05 were considered as statistically significant. Results Six ACCA centers participated in the project (Poland-2,Denmark-1,Spain-1,Italy-1,UK-1). Overall, 148 pts (age 62.9±15.27yrs; 27% female) were included. Main cause of OHCA was ACS 67 (45.27%), the most frequent initial rhythm was ventricular fibrillation VF 101 (68.24%). Median time to ROSC was 25 (15–35) min. In-hospital and 30 day mortality was 68 (46.9%) and 4 (5.33%), respectively. MOF with SOFA score ≥7 (high-risk of death) was noted in 100 (67.6%)pts at admission, and between 70 (59.82%) – 98 (74.8%)pts, thereafter. At least moderate respiratory failure was noted in 60 (42.5%)pts at admission, and between 10 (11%) – 37 (31%)pts, thereafter. SOFA score (Fig.1), respiratory failure at 24h (p=0.006) and 48h (p=0.013) after admission were positively correlated with in-hospital mortality. Early MOF expressed with SOFA score predicted the risk of 30-day mortality, with the strongest predictive value at 72h from admission OR 1.53 95% CI (1.29–1.82); p<0.001. Similarly, early respiratory failure predicted 30-day mortality, with the strongest predictive value at 24h of assessment OR 2.29 95% CI (1.44–3.66); p<0.001. SOFA score & mortality after OHCA Conclusions Patients after OHCA due to cardiac causes have a high-rate of MOF with high mortality early after the event. Those patients who survive to discharge have a relatively low 30-day mortality Multi-organ failure may predict early mortality after OHCA due to cardiac causes.

scholarly journals Pathological changes in the lungs and lymphatic organs of 12 COVID-19 autopsy cases

2020 ◽  
Vol 7 (12) ◽  
pp. 1868-1878
Author(s):  
Qian Liu ◽  
Yu Shi ◽  
Jun Cai ◽  
Yaqi Duan ◽  
Rongshuai Wang ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Immune Cell ◽  
Interstitial Fibrosis ◽  
Diffuse Alveolar Damage ◽  
Inflammatory Factors ◽  
Inflammatory Factor ◽  
Disease Characteristics ◽  
Spleen And Lymph Nodes ◽  
Lymphatic Organs ◽  
Macrophage Accumulation

Abstract Systematic autopsy and comprehensive pathological analyses of COVID-19 decedents should provide insights into the disease characteristics and facilitate the development of novel therapeutics. In this study, we report the autopsy findings from the lungs and lymphatic organs of 12 COVID-19 decedents—findings that evaluated histopathological changes, immune cell signature and inflammatory factor expression in the lungs, spleen and lymph nodes. Here we show that the major pulmonary alterations included diffuse alveolar damage, interstitial fibrosis and exudative inflammation featured with extensive serous and fibrin exudates, macrophage infiltration and abundant production of inflammatory factors (IL-6, IP-10, TNFα and IL-1β). The spleen and hilar lymph nodes contained lesions with tissue structure disruption and immune cell dysregulation, including lymphopenia and macrophage accumulation. These findings provide pathological evidence that links injuries of the lungs and lymphatic organs with the fatal systematic respiratory and immune malfunction in critically ill COVID-19 patients.

Tissue Characterization of Hypoxia, Nitric Oxide and Apoptosis Pathways in a Baboon Model of E. coli Sepsis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 138-138
Author(s):  
Lacramioara Ivanciu ◽  
Oana Herlea ◽  
Hua Zhu ◽  
Fletcher B. Taylor ◽  
Cristina Lupu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lymph Nodes ◽  
Mrna Expression ◽  
Organ Failure ◽  
Caspase 3 ◽  
No Production ◽  
E Coli ◽  
Peritubular Capillaries ◽  
Apoptosis Pathways ◽  
Spleen And Lymph Nodes

Abstract Sepsis - the most common cause of death in hospitalized patients -is characterized by severe inflammatory response and profound systemic vasculitic pathology accompanied by activation of blood coagulation. We observed previously that infusion of E. coli in baboons produced severe disruption of the microcirculation, such as capillary leakage, intravascular coagulation and tissue injury, which may lead to global tissue hypoxia, shock, organ failure, and death. Here, we report data on the temporal dynamics of tissue specific changes of hypoxia, nitric oxide (NO) and apoptosis pathways in response to sublethal or lethal E. coli challenge. Animals were administered sublethal doses of E. coli (LD30–50; 108 CFU/kg) and sacrificed after 2, 8 and 24 hours or lethal doses (LD100; 9x109 −1x1010 CFU/kg) for 8 hours. Both groups were compared to non challenged controls (n=3 per experimental condition). Six organs (lung, liver, heart, kidney, spleen and lymph nodes) were analyzed by immunofluorescence/confocal imaging for Hypoxia Inducible Factor 1 (HIF1α), NOS2, NOS3 nitrotyrosine (NT), inflammatory cell markers (myeloperoxidase and CD68 for neutrophils and macrophages, respectively), and apoptosis markers (active caspase-3, TUNEL, Bcl2, Bax). Tissue extracts were analyzed by ELISA (NT and caspase-3), dot and western blot (NT, Bcl2 and Bax) and RT-PCR and microarray assays for mRNA expression. The results show that HIF1α mRNA was increased by 2–3 fold, reaching maximum values at 2 hours in the lung and 24 hours in the liver. HIF1α nuclear translocation was detected by immunostaining at 8 hours in lung and 24 hours in the liver, especially in the LD100 E. coli challenged baboons. HIF1α functions as a master transcriptional regulator of the adaptive response to hypoxia, and controls the expression of over 40 genes including NOS2, an inducible enzyme that induces NO production and thus decreases the vascular tone, and VEGF, a very potent permeability factor. NOS2 mRNA and protein were induced after 8 hours mainly in inflammatory cells, while endothelial NOS3 showed a transient decrease at 2–8 hours, and increased at 24 hours as compared to controls. The overall increase in NO production was reflected in transient high levels of nitrosylated proteins at 8 hours in sublethal animals and persistent high levels in lethal baboons. Ultrastructural analysis of lung and kidney performed by electron microscopy showed signs of defective permeability, such as accumulation of plasma proteins in the lung alveolae and in the subendothelium of the kidney peritubular capillaries, concomitant with intra- and/or extravascular fibrin deposition. Dose-dependent induction of apoptosis was detected by TUNEL and caspase-3 staining, especially in the proximal contort tubes of the kidney, hepatocytes, lymphoid and pericapsular cells of spleen and lymph nodes. Mitochondrial manganese superoxide dismutase (SOD2), a protective enzyme produced in reaction to oxidative stress had a latter response, reaching the maximum mRNA expression at 8 hour in lung and 24 hours in the liver. Taken together, these results place hypoxia as a key factor in the development of organ dysfunction and multiple organ failure in sepsis and suggest that targeting hypoxia controlled transcription factors, such as HIF1α, or upregulating the antioxidant mechanisms may represent valuable therapeutic approaches.

Burnout among Teachers of the Gifted and Gifted Adults

1992 ◽  
Vol 8 (2) ◽  
pp. 107-113 ◽  
Author(s):  
David Willings
Keyword(s):  
Radical Change ◽  
Work Conditions ◽  
Existing Problems ◽  
Common Causes ◽  
Adults And Children ◽  
The Common ◽  
Service To Others ◽  
Gifted Adults ◽  
High Level ◽  
Highly Able

This article surveys some of the common causes of “burnout” such as: lack of rewards, irrelevant duties, unsatisfactory work conditions, lack of confirmation of worth and isolation. The writer also comments on the problems of lack of tangible feedback in many professions which provide service to others such as special educators and clergy who frequently deal with constant stress in others. Often a radical change in lifestyle compounds existing problems. In particular the paper discusses the “paralysed perfectionism” of highly able adults and children who initially were dedicated to reaching high level goals. The writer suggests keeping a daily Strategies Diary in which personal rewards and stresses are recorded and analysed with the purpose of reaching greater self-understanding.

Thirty-eight-negative-kinase-1 is a major mediator of trauma-induced intestinal injury and multi-organ failure

2018 ◽  
Vol 56 (08) ◽  
pp. e205-e206
Author(s):  
M Armacki ◽  
AK Trugenberger ◽  
A Ellwanger ◽  
T Eiseler ◽  
L Bettac ◽  
...  
Keyword(s):  
Organ Failure ◽  
Intestinal Injury ◽  
Multi Organ Failure ◽  
Major Mediator

Negotiations over Accounting Issues: The Congruency of Audit Partner and Chief Financial Officer Recalls

2005 ◽  
Vol 24 (s-1) ◽  
pp. 171-193 ◽  
Author(s):  
Michael Gibbins ◽  
Susan A. McCracken ◽  
Steven E. Salterio
Keyword(s):  
Negotiation Process ◽  
Chief Financial Officers ◽  
Chief Financial Officer ◽  
Relative Importance ◽  
Common Elements ◽  
Contextual Features ◽  
Large Numbers ◽  
The Common ◽  
High Level ◽  
Two Sides

Much of what takes place in auditor-client management negotiations occurs in unobservable settings and normally does not result in publicly available archival records. Recent research has increasingly attempted to probe issues relating to accounting negotiations in part due to recent events in the financial world. In this paper, we compare recalls from the two sides of such negotiations, audit partners, and chief financial officers (CFOs), collected in two field questionnaires. We examine the congruency of the auditors' and the CFOs' negotiation recalls for all negotiation elements and features that were common across the two questionnaires (detailed analyses of the questionnaires are reported elsewhere). The results show largely congruent recall: only limited divergences in recall of common elements and features. Specifically, we show a high level of congruency across CFOs and audit partners in the type of issues negotiated, parties involved in resolving the issue, and the elements making up the negotiation process, including agreement on the relative importance of various common accounting contextual features. The analysis of the common accounting contextual features suggests that certain contextual features are consistently important across large numbers of negotiations, whether viewed from the audit partner's or the CFO's perspective, and hence may warrant future study. Finally, the comparative analysis allows us to identify certain common elements and contextual features that may influence both audit partners and CFOs to consider the accounting negotiation setting as mainly distributive (win-lose).

Caged-electron States and Split-electron States in Endohedral Alkali C60

2021 ◽  
Author(s):  
yifan yang ◽  
Lorenz S Cederbaum
Keyword(s):  
State Of The Art ◽  
Electronic States ◽  
Electron States ◽  
The Common ◽  
High Level

The low-lying electronic states of neutral X@C60(X=Li, Na, K, Rb) have been computed and analyzed by employing state-of-the-art high level many-electron methods. Apart from the common charge-separated states, well known...

scholarly journals Soufeng sanjie formula alleviates collagen-induced arthritis in mice by inhibiting Th17 cell differentiation

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Di Hua ◽  
Jie Yang ◽  
Qinghai Meng ◽  
Yuanyuan Ling ◽  
Qin Wei ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Lymph Nodes ◽  
Inflammatory Cytokines ◽  
Th17 Cell ◽  
Collagen Induced Arthritis ◽  
Expression Levels ◽  
Th17 Cell Differentiation ◽  
Spleen And Lymph Nodes ◽  
Seed Coats

Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disease. Soufeng sanjie formula (SF), which is composed of scolopendra (dried body of Scolopendra subspinipes mutilans L. Koch), scorpion (dried body of Buthus martensii Karsch), astragali radix (dried root of Astragalus membranaceus (Fisch.) Bge), and black soybean seed coats (seed coats of Glycine max (L.) Merr), is a traditional Chinese prescription for treating RA. However, the mechanism of SF in treating RA remains unclear. This study was aim to investigate the anti-arthritic effects of SF in a collagen-induced arthritis (CIA) mouse model and explore the mechanism by which SF alleviates arthritis in CIA mice. Methods For in vivo studies, female DBA/1J mice were used to establish the CIA model, and either SF (183 or 550 mg/kg/day) or methotrexate (MTX, 920 mg/kg, twice/week) was orally administered to the mice from the day of arthritis onset. After administration for 30 days, degree of ankle joint destruction and serum levels of IgG and inflammatory cytokines were determined. The balance of Th17/Treg cells in the spleen and lymph nodes was analyzed using flow cytometry. Moreover, the expression levels of retinoic acid receptor-related orphan nuclear receptor (ROR) γt and phosphorylated STAT3 (pSTAT3, Tyr705) in the spleen were detected by immunohistochemistry. Furthermore, the effect of SF on Th17 cells differentiation in vitro was investigated in CD4+ T cells under Th17 polarization conditions. Results SF decreased the arthritis score, ameliorated paw swelling, and reduced cartilage loss in the joint of CIA mice. In addition, SF decreased the levels of bovine collagen-specific IgG in sera of CIA mice. SF decreased the levels of inflammatory cytokines (TNF-α, IL-6, and IL-17A) and increased the level of IL-10 both in the sera and the joint of CIA mice. Moreover, SF treatment rebalanced the Th17/Treg ratio in the spleen and lymph nodes of CIA mice. SF also reduced the expression levels of ROR γt and pSTAT3 (Tyr705) in the spleen of CIA mice. In vitro, SF treatment reduced Th17 cell generation and IL-17A production and inhibited the expression of RORγt, IRF4, IL-17A, and pSTAT3 (Tyr705) under Th17 polarization conditions. Conclusions Our results suggest that SF exhibits anti-arthritic effects and restores Th17/Treg homeostasis in CIA mice by inhibiting Th17 cell differentiation.

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