Abstract 14066: O -GlcNAc Levels Stimulation is a New Potential Therapeutic Strategy at the Early Phase of Septic Shock in the Young

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Thomas DUPAS ◽  
Manon DENIS ◽  
Justine Dontaine ◽  
Laurent Bultot ◽  
Antoine Persello ◽  
...  
Keyword(s):  
Septic Shock ◽  
Early Phase ◽  
Therapeutic Strategy ◽  
Troponin T ◽  
Post Translational Modification ◽  
Prism Score ◽  
Endotoxemic Shock ◽  
Old Rats ◽  
The Difference ◽  
The Impact

Background: We have shown that increase in O -GlcNAc levels, a post-translational modification involved in the stress response, at the early phase of septic shock in adult (84 days old rats) is a potential new therapeutic strategy. Most studies focus in adults while the population most affected by septic shock, young children, is rarely studied. Considering that O- GlcNAc levels are higher in the young, the impact of O- GlcNAc on septic shock in the young should be tested. Purpose: Evaluate if O- GlcNAc stimulation could improve sepsis outcomes in young. Methods: Endotoxemic shock was induced in 28 days old rats with an i.v. injection of saline (CTRL, n=10) or LPS (O111:B4, 20mg.kg -1 - LPS, n=9). 1 hour after LPS rats were randomly assigned to no therapy (LPS), fluidotherapy (saline, 10ml.kg -1 - LPS+R, n=10) ± NButGT (10 mg.kg -1 - NButGT, n=11) to increase O- GlcNAc levels. 2 hours later, physiological functions and markers of severity were measured and used in adapted Pediatric RISk of Mortality score (PRISM score). The impact of treatment on survival was evaluated on n=16 per group. Mass spectrometry (MS) study was performed to identify O -GlcNAcylated proteins. Results: LPS induce a shock (mean arterial pressure (MAP): CTRL: 67.2 ± 1.9; LPS: 50.7 ± 2.1; mmHg; p<0.05), alter biological parameters (lactates: CTRL: 3.92 ± 0.26; LPS: 6.42 ± 0.45; mmol.l -1 ; pH: CTRL: 7.27 ± 0.02; LPS: 7.15 ± 0.02; p<0.05), PRISM score (p<0.05) and is associated with multi organs dysfunction (troponin T: CTRL: 19.7 ± 4.0; LPS: 45.4 ± 11.4; ng.l -1 ; creatinine: CTRL: 15.9 ± 1.5; LPS: 25.3 ± 2.6; μmol.l -1 ; p<0.05). LPS+R has no beneficial effect while NButGT improves MAP (p<0.05), PRISM score (p<0.05) and the median survival (NButGT: 36.0; LPS+R: 13.65; hours; p<0.001) compared to LPS+R treatment. MS highlight important variations of O- GlcNAcylation particularly that of mitochondrial proteins. Conclusions: Despite higher O- GlcNAc levels, we demonstrate that O- GlcNAc stimulation is also a potential new therapeutic strategy for septic shock in young. Our results show that it is the difference between the basal levels and the post-stimulation levels which induces a protection against sepsis. Proteins identify by MS will need to be specifically studied to decipher their impact in septic shock.

scholarly journals Public health interventions and epidemic intensity during the 1918 influenza pandemic

2007 ◽  
Vol 104 (18) ◽  
pp. 7582-7587 ◽  
Author(s):  
Richard J. Hatchett ◽  
Carter E. Mecher ◽  
Marc Lipsitch
Keyword(s):  
Disease Transmission ◽  
Early Phase ◽  
Influenza Pandemic ◽  
Death Rates ◽  
Viral Spread ◽  
Early Implementation ◽  
The Difference ◽  
1918 Influenza ◽  
The Impact ◽  
Multiple Interventions

Nonpharmaceutical interventions (NPIs) intended to reduce infectious contacts between persons form an integral part of plans to mitigate the impact of the next influenza pandemic. Although the potential benefits of NPIs are supported by mathematical models, the historical evidence for the impact of such interventions in past pandemics has not been systematically examined. We obtained data on the timing of 19 classes of NPI in 17 U.S. cities during the 1918 pandemic and tested the hypothesis that early implementation of multiple interventions was associated with reduced disease transmission. Consistent with this hypothesis, cities in which multiple interventions were implemented at an early phase of the epidemic had peak death rates ≈50% lower than those that did not and had less-steep epidemic curves. Cities in which multiple interventions were implemented at an early phase of the epidemic also showed a trend toward lower cumulative excess mortality, but the difference was smaller (≈20%) and less statistically significant than that for peak death rates. This finding was not unexpected, given that few cities maintained NPIs longer than 6 weeks in 1918. Early implementation of certain interventions, including closure of schools, churches, and theaters, was associated with lower peak death rates, but no single intervention showed an association with improved aggregate outcomes for the 1918 phase of the pandemic. These findings support the hypothesis that rapid implementation of multiple NPIs can significantly reduce influenza transmission, but that viral spread will be renewed upon relaxation of such measures.

scholarly journals Impact of 1-Hour Bundle Achievement in Septic Shock

2020 ◽  
Author(s):  
Byuk Sung Ko ◽  
Sung-Hyuk Choi ◽  
Tae Gun Shin ◽  
Kyuseok Kim ◽  
You Hwan Jo ◽  
...  
Keyword(s):  
Septic Shock ◽  
Hospital Mortality ◽  
Odds Ratio ◽  
Multivariable Logistic Regression Analysis ◽  
Significant Difference ◽  
The Difference ◽  
The Impact ◽  
Over Time ◽  
Group 1 ◽  
Resuscitation Bundle

Abstract Background: Evidence supporting the association between 1-hour bundle achievement and patient outcomes is limited and inconsistent. Hence, this study aimed to address the impact of 1-hour bundle achievement on outcomes in septic shock patients.Methods: A prospective multicentre observational study of septic shock patients with a protocolised resuscitation bundle therapy at emergency departments was conducted from October 2015 to December 2018. In-hospital mortality according to 1-hour bundle achievement from shock recognition were compared using multivariable logistic regression analysis. Patients were also divided into six groups according to the time of bundle achievement and outcomes were compared to examine the difference in outcome for each group over time: group 1 (≤1 h; reference), 2 (1–2 h), 3 (2–3 h), 4 (3–4 h), 5 (4–5 h), and 6 (5–6 h). Results: In total, 1,612 patients with septic shock were included and in-hospital mortality was 18.2%. The 1-hour bundle was achieved in 461 (28.6%) patients. In multivariate analysis, the group achieving 1-hour bundle did not show a significant difference in in-hospital mortality compared to those who did not achieve 1-hour bundle (odds ratio = 0.74, confidence interval: 0.522–1.049, p = 0.091). However, groups 2, 3, 4, 5, and 6 showed significantly lower odds ratios of in-hospital mortality compared to those who did not achieve the bundle elements (odds ratio = 0.733, 0.604, 0.541, 0.532, and 0.458, respectively; p = 0.042, 0.001, < 0.001, 0.001, and < 0.001, respectively). There was no significant difference in in-hospital mortality over time for each group compared to that of group 1 used as a reference.Conclusion: One-hour bundle achievement was not associated with improved outcomes in septic shock patients with protocolised resuscitation bundle therapy. However, groups achieving 2-, 3-, 4-, 5-, and 6-hour bundle were associated more with improved outcome than those who did not. Further clinical trials are needed to clarify the clinical implications of 1-hour bundle achievement.

Molecular Forms of Human Protein C: Comparison and Distribution in Human Adult Plasma

1989 ◽  
Vol 62 (03) ◽  
pp. 902-905 ◽  
Author(s):  
Brian S Greffe ◽  
Marilyn J Manco-Johnson ◽  
Richard A Marlar
Keyword(s):  
Heavy Chain ◽  
Protein C ◽  
Molecular Forms ◽  
Post Translational Modification ◽  
Single Chain ◽  
Beta Form ◽  
Sds Page ◽  
Dependent Protein ◽  
Adult Plasma ◽  
The Difference

SummaryProtein C (PC) is a vitamin K-dependent protein which functions as both an anticoagulant and profibrinolytic. It is synthesized as a single chain protein (SC-PC) and post-transla-tionally modified into a two chain form (2C-PC). Two chain PC consists of a light chain (LC) and a heavy chain (HC). The present study was undertaken to determine the composition of the molecular forms of PC in plasma. PC was immunoprecipitated, subjected to SDS-PAGE and Western blotting. The blots were scanned by densitometry to determine the distribution of the various forms. The percentage of SC-PC and 2C-PC was found to be 10% and 90% respectively. This is in agreement with previous work. SC-PC and the heavy chain of 2C-PC consisted of three molecular forms (“alpha”, “beta”, and “gamma”). The “alpha” form of HC is the standard 2C form with a MW of 40 Kd. The “beta” form of HC has also been described and has MW which is 4 Kd less than the “alpha” form. The “gamma” species of the SC and 2C-PC has not been previously described. However, its 3 Kd difference from the “beta” form could be due to modification of the “beta” species or to a separate modification of the alpha-HC. The LC of PC was shown to exist in two forms (termed form 1 and form 2). The difference between these two forms is unknown. The molecular forms of PC are most likely due to a post-translational modification (either loss of a carbohydrate or a peptide) rather than from plasma derived degradation.

Evaluation of the impact of public investment programs on social and economic performance of territories

2019 ◽  
pp. 109-123
Author(s):  
I. E. Limonov ◽  
M. V. Nesena
Keyword(s):  
Bayesian Modeling ◽  
Positive Impact ◽  
Public Investment ◽  
Difference In Differences ◽  
The Public ◽  
Export Activity ◽  
Regional Investment ◽  
The Difference ◽  
The Impact ◽  
Development Institution

The purpose of this study is to evaluate the impact of public investment programs on the socio-economic development of territories. As a case, the federal target programs for the development of regions and investment programs of the financial development institution — Vnesheconombank, designed to solve the problems of regional development are considered. The impact of the public interventions were evaluated by the “difference in differences” method using Bayesian modeling. The results of the evaluation suggest the positive impact of federal target programs on the total factor productivity of regions and on innovation; and that regional investment programs of Vnesheconombank are improving the export activity. All of the investments considered are likely to have contributed to the reduction of unemployment, but their implementation has been accompanied by an increase in social inequality.

The Use of Multimedia and its Impact on Bangladeshi EFL Learners at Tertiary Level

2020 ◽  
Vol 4 (2) ◽  
pp. 150
Author(s):  
Farzana Sharmin Pamela Islam
Keyword(s):  
Language Learning ◽  
Academic Writing ◽  
Teaching And Learning ◽  
English Language ◽  
Capital City ◽  
Tertiary Level ◽  
Language Classroom ◽  
The Difference ◽  
The Government ◽  
The Impact

As 21st century is the era of modern technologies with different aspects, it offers us to make the best use of them. After tape recorder and overhead projector (OHP), multimedia has become an important part of language classroom facilities for its unique and effective application in delivering and learning lesson. Although in many parts of Bangladesh, a South Asian developing country, where English enjoys the status of a foreign language, the use of multimedia in teaching and learning is viewed as a matter of luxury. However, nowadays the usefulness and the necessity of it are well recognized by the academics as well as the government. The study aims to focus on the difference between a traditional classroom void of multimedia and multimedia equipped classrooms at university level by explaining how multimedia support the students with enhanced opportunity to interact with diverse texts that give them more in-depth comprehension of the subject. It also focuses on audio-visual advantage of multimedia on the students’ English language learning. The study has followed a qualitative method to get an in-depth understanding of the impact of using multimedia in an English language classroom at tertiary level. For this purpose, the data have been collected from two different sources. Firstly, from students’ written response to  an open ended question as to their comparative experience of learning  lessons with and without multimedia facilities; and secondly, through  observation of English language classes at a private university of Dhaka, the capital city of Bangladesh. The discussion of the study is limited to  the use of multimedia in English language classroom using cartoons, images and music with a view to enhance students’ skills in academic writing, critical analysis of image and critical appreciation of music. For this purpose, cartoons in English language, images from Google and music from You Tube have got focused discussion in this paper.

Case study: Prediction and field tests of railway noise and effects of a low-height noise barrier

2020 ◽  
Vol 68 (4) ◽  
pp. 303-314
Author(s):  
Yuna Park ◽  
Hyo-In Koh ◽  
University of Science and Technology, Transpo ◽  
University of Science and Technology, Transpo ◽  
University of Science and Technology, Transpo ◽  
...  
Keyword(s):  
High Speed ◽  
Field Tests ◽  
Residential Areas ◽  
Railway Systems ◽  
Railway Noise ◽  
Sound Levels ◽  
Noise Barrier ◽  
The Difference ◽  
Reduction Effect ◽  
The Impact

Railway noise is calculated to predict the impact of new or reconstructed railway tracks on nearby residential areas. The results are used to prepare adequate counter- measures, and the calculation results are directly related to the cost of the action plans. The calculated values were used to produce noise maps for each area of inter- est. The Schall 03 2012 is one of the most frequently used methods for the production of noise maps. The latest version was released in 2012 and uses various input para- meters associated with the latest rail vehicles and track systems in Germany. This version has not been sufficiently used in South Korea, and there is a lack of standard guidelines and a precise manual for Korean railway systems. Thus, it is not clear what input parameters will match specific local cases. This study investigates the modeling procedure for Korean railway systems and the differences between calcu- lated railway sound levels and measured values obtained using the Schall 03 2012 model. Depending on the location of sound receivers, the difference between the cal- culated and measured values was within approximately 4 dB for various train types. In the case of high-speed trains, the value was approximately 7 dB. A noise-reducing measure was also modeled. The noise reduction effect of a low-height noise barrier system was predicted and evaluated for operating railway sites within the frame- work of a national research project in Korea. The comparison of calculated and measured values showed differences within 2.5 dB.

MicroRNA-520c-3p Modulates Doxorubicin-Chemosensitivity in HepG2 Cells

2020 ◽  
Vol 21 (2) ◽  
pp. 237-245 ◽  
Author(s):  
Mohamed A. Ragheb ◽  
Marwa H. Soliman ◽  
Emad M. Elzayat ◽  
Mervat S. Mohamed ◽  
Nada El-Ekiaby ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Therapeutic Strategy ◽  
Suppressive Effect ◽  
Expression Level ◽  
Tumor Suppressor Function ◽  
Protein Expression Level ◽  
Blot Technique ◽  
Induction Of Apoptosis ◽  
The Impact

Background: Doxorubicin (DOX) is the most common drugs used in cancer therapy, including Hepatocellular Carcinoma (HCC). Drug resistance, is one of chemotherapy’s significant problems. Emerging studies have shown that microRNAs (miRNAs) could participate in regulating this mechanism. Nevertheless, the impact of miRNAs on HCC chemoresistance is still enigmatic. Objective: Investigating the role of miR-520c-3p in enhancement of anti-tumor effect of DOX against HepG2 cells. Methods: Expression profile for liver related miRNAs (384 miRNAs) has been analyzed on HepG2 cells treated with DOX using qRT-PCR. miR-520c-3p, the most deregulated miRNA, was selected for combination treatment with DOX. Expression level for LEF1, CDK2, CDH1, VIM, Mcl-1 and TP53 was evaluated in miR-520c-3p transfected cells. Cell viability, colony formation, wound healing as well as apoptosis assays have been demonstrated. Furthermore, Mcl-1 protein level was measured using western blot technique. Results: The present data indicated that miR-520c-3p overexpression could render HepG2 cells chemo-sensitive to DOX through enhancing its suppressive effects on proliferation, migration, and induction of apoptosis. The suppressive effect of miR-520c-3p involved altering the expression levels of some key regulators of cell cycle, proliferation, migration and apoptosis including LEF1, CDK2, CDH1, VIM, Mcl-1 and TP53. Interestingly, Mcl-1 was found to be one of the potential targets of miR-520c-3p, and its protein expression level was down-regulated upon miR-520c-3p overexpression. Conclusion: Our data referred to the tumor suppressor function of miR-520c-3p that could modulate chemosensitivity of HepG2 cells toward DOX treatment, providing a promising therapeutic strategy in HCC.

scholarly journals Soil Moisture Dynamics in Response to Precipitation and Thinning in a Semi-Dry Forest in Northern Mexico

Water ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 105
Author(s):  
Argelia E. Rascón-Ramos ◽  
Martín Martínez-Salvador ◽  
Gabriel Sosa-Pérez ◽  
Federico Villarreal-Guerrero ◽  
Alfredo Pinedo-Alvarez ◽  
...  
Keyword(s):  
Soil Moisture ◽  
Forest Management ◽  
Water Availability ◽  
Dry Forest ◽  
Rainfall Events ◽  
Rainfall Characteristics ◽  
Northern Mexico ◽  
The Difference ◽  
The Impact ◽  
Moisture Dynamics

Understanding soil moisture behavior in semi-dry forests is essential for evaluating the impact of forest management on water availability. The objective of the study was to analyze soil moisture based in storm observations in three micro-catchments (0.19, 0.20, and 0.27 ha) with similar tree densities, and subject to different thinning intensities in a semi-dry forest in Chihuahua, Mexico. Vegetation, soil characteristics, precipitation, and volumetric water content were measured before thinning (2018), and after 0%, 40%, and 80% thinning for each micro-catchment (2019). Soil moisture was low and relatively similar among the three micro-catchments in 2018 (mean = 8.5%), and only large rainfall events (>30 mm) increased soil moisture significantly (29–52%). After thinning, soil moisture was higher and significantly different among the micro-catchments only during small rainfall events (<10 mm), while a difference was not noted during large events. The difference before–after during small rainfall events was not significant for the control (0% thinning); whereas 40% and 80% thinning increased soil moisture significantly by 40% and 53%, respectively. Knowledge of the response of soil moisture as a result of thinning and rainfall characteristics has important implications, especially for evaluating the impact of forest management on water availability.

scholarly journals The impact of non-pharmaceutical interventions on COVID-19 epidemic growth in the 37 OECD member states

2021 ◽  
Author(s):  
Francisco Pozo-Martin ◽  
Heide Weishaar ◽  
Florin Cristea ◽  
Johanna Hanefeld ◽  
Thurid Bahr ◽  
...  
Keyword(s):  
Growth Rate ◽  
Early Phase ◽  
Policy Decision ◽  
Multilevel Modelling ◽  
Daily Growth ◽  
Public Places ◽  
Member States ◽  
Unit Increase ◽  
Policy Decision Making ◽  
The Impact

AbstractWe estimated the impact of a comprehensive set of non-pharmeceutical interventions on the COVID-19 epidemic growth rate across the 37 member states of the Organisation for Economic Co-operation and Development during the early phase of the COVID-19 pandemic and between October and December 2020. For this task, we conducted a data-driven, longitudinal analysis using a multilevel modelling approach with both maximum likelihood and Bayesian estimation. We found that during the early phase of the epidemic: implementing restrictions on gatherings of more than 100 people, between 11 and 100 people, and 10 people or less was associated with a respective average reduction of 2.58%, 2.78% and 2.81% in the daily growth rate in weekly confirmed cases; requiring closing for some sectors or for all but essential workplaces with an average reduction of 1.51% and 1.78%; requiring closing of some school levels or all school levels with an average reduction of 1.12% or 1.65%; recommending mask wearing with an average reduction of 0.45%, requiring mask wearing country-wide in specific public spaces or in specific geographical areas within the country with an average reduction of 0.44%, requiring mask-wearing country-wide in all public places or all public places where social distancing is not possible with an average reduction of 0.96%; and number of tests per thousand population with an average reduction of 0.02% per unit increase. Between October and December 2020 work closing requirements and testing policy were significant predictors of the epidemic growth rate. These findings provide evidence to support policy decision-making regarding which NPIs to implement to control the spread of the COVID-19 pandemic.

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