Dissimilar Impact Research Articles

Stochastic time series analysis of atrial fibrillatory electrograms in paroxysmal atrial fibrillation

Abstract Background/Introduction Regional dominant frequency and instantaneous frequency modulation of short fractionated atrial electrograms have been associated with ablation targets and the prognosis of atrial fibrillation (AF). However, inconsistent and not fully comprehensible results have been reported. Purpose To construct a simple computational algorithm for the analysis of continuous fibrillatory atrial electrograms and evaluate it in clinical practice, among patients with paroxysmal AF. Methods Before the first cryo-balloon ablation, 3-minute continuous local electrogram recordings during pace-induced AF were obtained by the circumferential catheter from the left atrial appendage (LAA) and each pulmonary vein: left superior (LSPV), left inferior (LIPV), right superior (RSPV) and right inferior (RIPV). Following time- and frequency-domain analysis, non-linear detrended fluctuation analysis (DFA α) with analysis for short-term (DFA α1) and long-term fluctuations (DFA α2) was performed. The signals were detrended by subtracting time series polynomial fit and badpass filtered in the MATLAB environment (cut-off voltage 0.1 mV to avoid scar and artifacts). Results Fifteen patients were studied. Among different atrial areas, higher mean peak rate (pr) along with lower standard deviation of between peaks intervals (sdpp) and root square of peak-to-peak differences (rmppd) were observed in the LAA and left veins (Fig. 1). In patients with longer AF history (> 2 yrs), lower α, α1 and α2 exponents of DFA were observed (Fig. 2). Conclusions This algorithm depicted dissimilar impact on atrial electrical activity between different atrial areas. Patients with longer AF history had less self-similarity in local LAA electrograms. This might indicate possible ablation targets and reveal patients with greater AF burden and worse arrhythmic prognosis.Leftheriotis - Figure 1Leftheriotis - Figure 2

CB1R chronic intermittent pharmacological activation facilitates amphetamine seeking and self-administration and changes in CB1R/CRFR1 expression in the amygdala and nucleus accumbens in rats

Patterns of drug ingestion may have a dissimilar impact on the brain, and therefore also the development of drug addiction. One pattern is binge intoxication that refers to the ingestion of a high amount of drug on a single occasion followed by an abstinence period of variable duration. In this study, our goal was to contrast the effect of continuous low amounts with intermittent higher amounts of Arachidonyl-chloro-ethylamide (ACEA), a CB1R agonist, on amphetamine seeking and ingestion, and describe the effects on the expression of CB1R and CRFR1 in the central nucleus of the amygdala (CeA) and in the nucleus accumbens shell (NAcS). Adult male Wistar rats were treated with a daily administration of vehicle or 20 μg of ACEA, or four days of vehicle followed by 100 μg of ACEA on the fifth day, for a total of 30 days. Upon completion of this treatment, the CB1R and CRFR1 expression in the CeA and NAcS was evaluated by immunofluorescence. Additional groups of rats were evaluated for their anxiety levels (elevated plus maze, EPM), amphetamine (AMPH) self-administration (ASA) and breakpoint (A-BP), as well as AMPH-induced conditioned place preference (A-CPP). Results indicated that ACEA induced changes in the CB1R and CRFR1 expression in both the NAcS and CeA. An increase in anxiety-like behavior, ASA, A-BP and A-CPP was also observed. Since the intermittent administration of 100 μg of ACEA induced the most evident changes in most of the parameters studied, we concluded that binge-like ingestion of drugs induces changes in the brain that may make the subject more vulnerable to developing drug addiction.

Damage characteristics and fracture behaviour of marble after cycle impact loading

Rock masses in underground engineering projects, such as roadways or pillars, are inevitably subjected to cyclic dynamic loading, and the damage behaviour of jointed rock masses is often influenced by the different characteristics of the preexisting rock damage. To investigate the effect of cyclic impact on the fracture characteristics of rocks, fracture tests were conducted using SCC (short core in compression) specimens with dissimilar impact damage. The experimental results showed that cyclic impact led to mesoscale fracture and strength deterioration in rock specimens. As the number of impacts increased, the dynamic peak stress of marble decreased, and the maximum strain and the energy absorbed by marble increased. At the same time, cyclic impacts generated continuous damage to the interior of the specimen, and the white spot inside the specimen with higher impact times was more obvious. Based on the fracture test results, the mode II fracture toughness was calculated, and it decreased by 6.9, 20.9, 43.3, 66.8, and 87.0% for specimens that underwent 1–5 cyclic impacts, respectively. After fracture, the three-dimensional topography characteristics of the fracture surface were obtained by a 3D optical scanner. Overall, the fracture surface became increasingly tortuous with increasing impact number. For the fractal factor D, the variation in the mean squared deviation of the asperity height and slope angle exhibited an increasing tendency with an increasing number of impacts.

The Dissimilar Impact in Atrial Substrate Modificationof Left and Right Pulmonary Veins Isolation after Catheter Ablation of Paroxysmal Atrial Fibrillation.

Since the discovery of pulmonary veins (PVs) as foci of atrial fibrillation (AF), the commonest cardiac arrhythmia, investigation revolves around PVs catheter ablation (CA) results. Notwithstanding, CA process itself is rather neglected. We aim to decompose crucial CA steps: coronary sinus (CS) catheterization and the impact of left and right PVs isolation (LPVI, RPVI), separately. We recruited 40 paroxysmal AF patients undergoing first-time CA and obtained five-minute lead II and bipolar CS recordings during sinus rhythm (SR) before CA (B), after LPVI (L) and after RPVI (R). Among others, duration, amplitude and atrial-rate variability (ARV) were calculated for P-waves and CS local activation waves (LAWs). LAWs features were compared among CS channels for reliability analysis. P-waves and LAWs features were compared after each ablation step (B, L, R). CS channels: amplitude and area were different between distal/medial () and distal/mid-proximal channels (). Medial and distal showed the most and least coherent values, respectively. Correlation was higher in proximal (≥93%) than distal (≤91%) areas. P-waves: duration was significantly shortened after LPVI (after L: ). LAWs: insignificant variations. ARV modification was more prominent in LAWs (L: >+73.12%, , R: <−33.94%, ). Medial/mid-proximal channels are recommended during SR. CS LAWs are not significantly affected by CA but they describe more precisely CA-induced ARV modifications. LPVI provokes the highest impact in paroxysmal AF CA, significantly modifying P-wave duration.

Nanoparticles Impression on Creatine Kinase Activity

Nanoparticles (NPs) are purchased from Sigma-Aldrich (730785). Sodium citrate as stabilizer comprises 10 nm particle size (TEM), dispersion (NPs), stabilizer Silver, and 0.02 mg/mL in aqueous buffer relative molecular mass (107.87). The concentration number (3.6×1012) packaging 25mL in a glass bottle. 10 nm diameter golden nanoparticles OD 1, stable 0.1 mM suspension is an aqueous salt solution that contains common salt, dihydrogen phosphate, and dilute phosphate-buffered saline (PBS). It also contains potassium dihydrogen phosphate and potassium chloride in certain formulations. While the pH rises, the role of the buffer is to regulate it. NPs, equipped with (Sigma-Aldrich752584) relative molecular mass (196.97). Structural and optical nanoparticles are studied. Findings show a nanoparticle size of approximately 10 nanometers. The silver and gold sources’ impact on healthy people’s creatine kinase (CK) activity within the blood was in vitro-studied. The results indicated that the nanoparticles of silver and gold had a dissimilar impact on serum CK activity. The gold particles tonic impacts serum CK activity and increases the activity of enzymes as the concentration of nanoparticles increases because it acts as an enzyme activator. At the same time, silver nanoscale has an inhibitory effect thereon.

Impact responses of precast hollow reinforced concrete beams with prestress tendons using high-fidelity physics-based simulations

This study investigates the dynamic response, damage mechanisms, and residual capacity of precast hollow reinforced concrete beams with prestress tendons (HRCBPT) under impact loads by using High-Fidelity Physics-Based (HFPB) finite element (FE) models. The accuracy of the numerical model developed in this study has been fully calibrated against two different drop-weight impact tests available in open literature, including a scaled hollow reinforced concrete beam (HRCB) and a full-scale reinforced concrete (RC) beam. The results in this study show that under low to moderate impact loads, the flexural cracks and global deformation of the HRCBPT are similar to the hollow beam with normal reinforcement. Under high impact loads, although these beams exhibit similar diagonal shear cracks near the impact location, the HRCBPT experiences more local concrete spalling damage on the bottom flange, higher residual capacity index, and smaller reaction force at supports owing to the contribution of the initial prestress force. The results also suggest that the maximum compressive stress at the bottom flange of the section should be smaller than 17.6% of its compressive strength in order to maximise the beam’s impact-resistant capacity, while the prestress level in the tendon should be lower than 65% of the tendon yield strength to prevent premature failure under moderate impact conditions. Furthermore, different combinations of the impact velocity and impact mass would generate different impact force profiles on the beam resulting in dissimilar impact responses and residual capacity. In the design analysis, together with the critical impact location at the mid-span, the impact location close to the supports which may cause critical shear response of the beam, also needs be considered. In this study, the impact in the vicinity of the support yields the most severe damage to the beam resulting in the lowest residual capacity.

High strength impact welding of 7075 Al to a SiC-reinforced aluminum metal matrix composite

Vaporizing foil actuator welding (VFAW), an impact welding method, was used for the first time to produce high strength welds between SiC-reinforced 8009 aluminum metal matrix composite (MMC) (8009/SiC/11p) and 7075 aluminum alloy (AA7075). Microscopic characterization of the dissimilar impact weld revealed multiple heterogenous microstructural zones including an unbonded zone at the center, a flat interface, a wavy interface, and a trapped jet zone at the corner. SiC-depleted and SiC-rich bands were alternately distributed with consistent plastic flow patterns along the wavy interface. Microhardness tests prove that little or no heat or mechanically affected zones were formed in the dissimilar impact weld. Peel test yields a nugget pullout on the AA7075-T6 indicating high strength of the weld. VFAW process provides a solution to join the Al MMC with dissimilar metals in the applications of automotive and aerospace products.

SYSTEM OF AUTOMATIC DETERMINATION OF TEXT TONE

In the work, the methods of sentiment analysis of the text are considered. The system of emotion detection of Ukrainian-language texts based on dictionaries and rules is proposed. The developed software downloads text information in various formats and carries out tokenization and lemmatization procedures using the Python TokenizeUKand pymorphy2 libraries. As a result, an array of words in the basic grammatical form using for determining the tone of the text is formed. The obtained word base was analyzed using a tonal dictionary of the Ukrainian language. A dictionary of synonyms was used to expand the vocabulary. If there is no word in the tonal dictionary, the tonality value of its nearest synonym is used for further calculations. Computer analysis of textual information was performed in five emotional categories namely: very positive, positive, neutral, negative, and very negative tone of words. To increase the accuracy and validity of sentiment analysis, coefficients were used that take into account the various emotional load of words of different speech parts and their dissimilar impact on the overall assessment of the text tone. The proposed system of sentiment analysis assumes a greater emotional influence of adjectives compared to verbs and nouns. Since the tone of textual information and the expression of human emotions are subjective factors, the means of fuzzy modeling are used for sentiment analysis of texts. This approach makes it possible to take into account the contribution of all emotional categories in the final evaluation of the text. As a result of an aggregation of normalized data on different emotion categories and defuzzification by the method of the center of gravity for one-element sets, a quantitative estimate of the emotional tone of texts was obtained. The developed system of sentiment analysis was tested on Ukrainian-language texts from different sources and different emotional tones. The use of additional tools provides the analysis of more words in the text and the degree of their emotional tone, which leads to more correct detection of the tone of the whole text. Key words : computer text analysis, sentiment analysis, tokenization, tonality dictionary, fuzzy modeling.

Metagenomic analysis reveals the fate of antibiotic resistance genes in two-stage and one-stage anaerobic digestion of waste activated sludge

Waste activated sludge (WAS) from wastewater treatment plants is an important reservoir of antibiotic resistance genes (ARGs). The fate of ARGs in this process was not revealed previously. The present study applied metagenomic approach to examine the occurrence and fate of ARGs in thermophilic alkaline fermentation followed by mesophilic anaerobic digestion (TM), by comparison with mesophilic alkaline fermentation followed by mesophilic anaerobic digestion (MM) and one-stage mesophilic anaerobic digestion (M) process. The removal efficiency of two-stage anaerobic digestion (AD) to total ARGs is higher than that of one-stage AD. The hydrogen and methane production stages of two-stage AD processes have dissimilar impact on the fate of ARGs. Macrolide, lincosamide, and streptogramin (MLS) resistance genes were enriched, especially in the hydrogen production reactors of TM and MM processes. Statistical analysis of metagenomic profiles analysis suggested that bacA may be the differential ARG subtype of two-stage AD process. ARG-like sequences encoding antibiotic efflux pump, antibiotic inactivation and antibiotic target alteration mechanisms were identified as the dominant ARGs resistance mechanisms in all samples. Procrustes analysis showed that microbial community composition structured the resistome. Co-occurrence patterns between ARGs and microbial phylogeny revealed that 26 bacterial species might be potential hosts of 94 ARG subtypes.

Aging differentially impacts vasodilation and angiogenesis in arteries from the white and brown adipose tissues.

Aging adipose tissues (ATs) manifest reduced vascularity and increased hypoxia and inflammation that contribute to local and systemic metabolic dysfunction. However, the mechanisms that underlie these age-related changes are incompletely understood. In this study, we sought to examine insulin-stimulated vasodilation and angiogenesis in the arterial vasculature from three major AT depots, perigonadal white (pgWAT), subcutaneous white (scWAT) and brown (BAT) from young and old mice. Here, we demonstrate that in young mice, insulin-stimulated vasodilation is lower in feed arteries from pgWAT compared to scWAT (p<0.05), but no differences were found between feed arteries in other AT depots (p>0.05). Insulin-stimulated vasodilation was lower in old compared to young feed arteries from all three AT depots (p<0.05 for all). In the presence of endothelial nitric oxide synthase inhibitor, L-NAME, insulin-stimulated vasodilation was decreased in young (p<0.05), but was unaffected in old (p>0.05) from all AT depots. We also observed no age-related differences in endothelium-independent dilation, as assessed by sodium nitroprusside (p>0.05). We next investigated angiogenic capacity of the vasculature in these AT depots. In young mice, BAT vasculature demonstrated the highest angiogenic potential, followed by pgWAT and scWAT. We found that aging decreased angiogenic sprout formation in pgWAT and BAT (both p<0.05), but increased angiogenic potential in scWAT (p<0.05), indicating dissimilar impact of aging on angiogenesis in different AT depots. Collectively, these data suggest that aging leads to a consistent impairment in insulin-stimulated vasodilation and reduction in NO bioavailability in all three AT, although aging differentially impacts angiogenic capacity across different AT depots.

Impact of career shocks on Indian MBA careers: an exploratory study

PurposeThe study explores career shocks in the Indian context and examines their impact on the career development of people with MBAs.Design/methodology/approachIn-depth, semi-structured interviews with 41 Indian MBA graduates were thematically analysed to identify career shocks that resulted in different types of transitions. Eight themes were identified based on ongoing and iterative comparison of these instances.FindingsOutcomes relating to competitive examinations that determined entry into various occupations were the first career shock experienced by participants. Geographical considerations were salient in the deliberations involving events relating to marriage, eldercare and spouse relocation. Events at the workplace that signalled uncertainty, a fall-out with one's boss or a request to relocate, prompted participants to switch employers. Some of the observed differences were gender based. While female MBA graduates adapted to handle both spousal and parental responsibilities, male MBA graduates did the same to shoulder eldercare responsibilities.Research limitations/implicationsThe study's retrospective design could have led to concerns regarding memory recall. The use of open-ended questions partially mitigated this, by giving participants the freedom to recount their experiences, to the extent that they could remember.Practical implicationsOrganisations in India could customise and strengthen policies to support employees who have maternity and eldercare responsibilities. Managers should make greater efforts to have open communication with their subordinates to overcome the challenges of operating in a culture with high power distance and indirect communication styles.Originality/valueThis study explored different types of career shocks and associated transitions. The Indian context, with its growing economy, large population, collectivistic culture and strong influence of family on careers, enabled a deeper examination of novel career shocks. The study also highlighted the dissimilar impact of career shocks for men and women and people at different career stages.

Ideological proximity and voter turnout in multi-level systems: evidence from Spain

ABSTRACT Does ideological proximity between the individual and political parties determine electoral participation in regional elections, as much as in national elections? Does the degree of self-rule of a region affect the interplay between ideological distance and turnout? This article addresses these questions and provides empirical evidence drawing upon individual-level and regional-level data from 53 regional elections and 4 national elections in Spain. Results indicate that citizens are more likely to vote when they perceive there is at least one congruent policy option among the party supply, and this happens at both regional and national levels. However, whether the closest party is in national government or whether it is a regionalist organization has a dissimilar impact on turnout in different tiers. This relationship between the type of party which is most ideologically proximate and electoral participation is partially affected by the degree of regional autonomy of the territory.

Mathematical model of hypoxia and tumor signaling interplay reveals the importance of hypoxia and cell-to-cell variability in tumor growth inhibition

BackgroundHuman tumor is a complex tissue with multiple heterogeneous hypoxic regions and significant cell-to-cell variability. Due to the complexity of the disease, the explanation of why anticancer therapies fail cannot be attributed to intrinsic or acquired drug resistance alone. Furthermore, there are inconsistent reports of hypoxia-induced kinase activities in different cancer cell-lines, where increase, decreases, or no change has been observed. Thus, we asked, why are there widely contrasting results in kinase activity under hypoxia in different cancer cell-lines and how does hypoxia play a role in anti-cancer drug sensitivity?ResultsWe took a modeling approach to address these questions by analyzing the model simulation to explain why hypoxia driven signals can have dissimilar impact on tumor growth and alter the efficacy of anti-cancer drugs. Repeated simulations with varying concentrations of biomolecules followed by decision tree analysis reveal that the highly differential effects among heterogeneous subpopulation of tumor cells could be governed by varying concentrations of just a few key biomolecules. These biomolecules include activated serine/threonine-specific protein kinases (pRAF), mitogen-activated protein kinase kinase (pMEK), protein kinase B (pAkt), or phosphoinositide-4,5-bisphosphate 3-kinase (pPI3K). Additionally, the ratio of activated extracellular signal-regulated kinases (pERK) or pAkt to its respective total was a key factor in determining the sensitivity of pERK or pAkt to hypoxia.ConclusionThis work offers a mechanistic insight into how hypoxia can affect the efficacy of anti-cancer drug that targets tumor signaling and provides a framework to identify the types of tumor cells that are either sensitive or resistant to anti-cancer therapy.

Determinants of Capital Structure in Selected Chinese Industries: A Panel Data Approach

This study explored the determinants of the capital structure in selected Chinese industries for a period of seven years (from 2011- 2016). Using the ex-post facto design, secondary data was collected from the Chinese Stock Exchange (CSE), seven determinants of capital structure were analyzed. These determinants are growth opportunities, size, profitability, and tangibility and non-debt tax shields, ownership structure and sales revenue. The Trade-off theory and Pecking Order theory were employed as the theoretical anchorage of the study. Panel data was used to construct the model with accompanying descriptive statistics such as means and standard deviation and inferential statistics such as Correlation matrix, F-test, Hausman test, LM test, two-stage least squares (2SLS) and General Method of Moments (GMM) to establish endogeneity. Empirical results from the study showed that the growth opportunities generally had direct influence on short-term debt levels and inverse correlation with total debt ratio and long-term debt ratio which pre-empts that all leverage measures are not same and would have a dissimilar and unique impact on the explanatory variables. Same relation was observed for all the variables especially - volatility of earnings, non-debt tax shield and ownership structure in terms of association and effect. The regression results showed that company size and capital structure are directly correlated while volatility of earnings and capital structure are inversely related. Keywords: Capital Structure, Trade off theory, Pecking Order Theory DOI : 10.7176/EJBM/11-8-02 Publication date :March 31 st 2019

Employee Voluntary and Involuntary Turnover and Organizational Performance: Revisiting the Hypothesis from Classical Public Administration

ABSTRACT:This article examines the effects of voluntary, involuntary, and absolute turnover rates on organizational performance. Adopting human capital and cost-benefit theories, this article posits that voluntary and involuntary turnover would have a linear negative and an inverted U-shaped relationship with organizational performance, respectively, and that an absolute turnover measure can prevent us from revealing the distinct effects of different types of turnover. Using four years of data from Florida school districts, primary findings suggest that involuntary turnover has an inverted U-shaped relationship with organizational performance, first positive and then negative, while the relationship between voluntary turnover and organizational performance remains inconclusive. The findings also suggest that absolute turnover rates can mask the complex and dissimilar impact that various types of turnover have on organizational performance.

Assessment of Heavy Metals Contamination in Drinking Water of Garmian Region, Iraq

Drinking water of safe quality is a critical issue for human survival and health. Water pollution by heavy metals is very crucial because of their toxicity. This study assesses potential of heavy metals pollution in drinking water in Garmian Region, East Iraq. Water samples were investigated for 23 heavy metals and 6 chemical contaminants collected from 16 locations. The analysis was performed by using coupled plasma optical emission spectroscopy (ICPOES, Spectro Arcos). High levels of Al, Se, Sr, and Fe have been detected at certain locations in study area. Statistical analysis techniques of the correlation matrix (CM), and cluster hierarchical analysis (CA) were conducted. The heavy metals pollution index (HPI), heavy metals evaluation index (HEI), and contamination Index (Cd) were used applied. These indices linked with the statistical analysis to interpret relationships among the tested parameters in water samples and to investigate the pollution sources over the study region. Even with the significant correlations between the HPI, Cd, and HEI, they showed dissimilar impact of examined heavy metals on the water quality. The most reliable pollution evaluation index of HEI for drinking water showed that 44% of the water samples is critically polluted. Sources of the contamination are most likely coming from natural geological sources. Anthropogenic impact was only noticed at several sites in the study area.

Dissimilar impact of type 2 diabetes on cardiovascular outcomes according to age categories: a nationwide population study from Hungary

BackgroundThe excess risks of mortality and cardiovascular morbidity among patients with type 2 diabetes mellitus (T2DM) is well known. In this nationwide study, we assessed risks of mortality and cardiovascular events comparing patients with T2DM and matched controls.MethodsWe identified patients with T2DM in a retrospective cohort study using the database of the National Health Insurance Fund between 1 January 2010 and 31 December, 2013. Controls were randomly included and matched according to age, gender, and zip code of residence. Patients were divided into subgroups according to age decades for outcome analyses.ResultsDuring the mean follow-up period of 2.3 years, 152,678 patients with T2DM and 305,356 matched controls were included. Patients with T2DM showed significantly higher risk for all-cause mortality (HR 1.26, 95% CI 1.22–1.29, p < 0.0001), myocardial infarction (HR 1.81, 95% CI 1.69–1.94, p < 0.0001) and stroke (HR 1.40, 95% CI 1.35–1.46, p < 0.0001) compared to matched controls. The higher risk associated with T2DM for mortality, myocardial infarction and stroke differed significantly between age groups (pinteraction < 0.05 for all outcomes) with significantly higher risk observed in younger patients.ConclusionsThe risk of cardiovascular outcomes and all-cause mortality is significantly higher in patients with T2DM. Notably, the relative hazard increases with decreasing age suggesting that younger patients with T2DM should receive more attention for cardiovascular prevention.

An Entrogram‐Based Approach to Describe Spatial Heterogeneity With Applications to Solute Transport in Porous Media

AbstractThe recently introduced geological entropy concept evaluates spatial order/disorder in the structure of the hydraulic conductivity (K) field to explain and predict certain characteristics of transport behavior. This concept is expanded in this work by introducing a novel tool for spatial analysis called entrogram from which a metric called entropic scale (HS) can be calculated to measure the overall persistency of patterns of spatial association in a distributed field and to allow robust comparisons between different spatial structures. The entrogram and the entropic scale concepts are applied here to investigate the link between solute transport behavior and the spatial structure of K fields modeled as the distribution of three hydrofacies in alluvial aquifers. Accurate empirical relationships are found between HS and key transport quantities confirming the clear correlation between transport and the structure of the K field described in terms of its entropic scale. The entrogram analysis is also applied to continuous 2‐D and 3‐D fields having identical lognormal K distributions, but with different connectivity. Comparisons between the entrograms and the calculated HS values for these fields, as well as for their corresponding flow velocity distributions, shed light on the key differences among these structures in 2‐D and in 3‐D, which in turn explain their dissimilar impact on solute transport. The entrogram‐based interpretation of the transport simulations seems to confirm that the geological entropy is a promising approach for predicting solute transport behavior simply from a description of the K field heterogeneity.

Immunomodulating peptides derived from different human endogenous retroviruses (HERVs) show dissimilar impact on pathogenesis of a multiple sclerosis animal disease model

Retroviruses including Human Endogenous Retroviruses (HERVs), contain a conserved region with highly immunomodulatory functions in the transmembrane proteins in envelope gene (env) named immunosuppressive domain (ISU).In this report, we demonstrate that Env59-GP3 peptide holds therapeutic potential in a mouse model of myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). The results show that this specific HERV-H derived ISU peptide, but not peptide derived from another env gene HERV-K, decreased the development of EAE in C57BL/6 mice, accompanied by reduced demyelination and inhibition of inflammatory cells. Moreover, here we tested the effect of peptides on macrophages differentiation. The treatment with Env59-GPS peptide modulate the pro-inflammatory M1 profile and anti-inflammatory M2 macrophages, being shown by inhibiting inflammatory M1 hallmark genes/cytokines expression and enhancing expression of M2 associated markers. These results demonstrate that Env59-GP3 ISU peptide has therapeutic potential in EAE possibly through inducing the polarization of M2 macrophages and inhibiting inflammatory responses.

Interplay of grade and stage on survival outcomes in appendiceal adenocarcinoma: Corroboration of the AJCC (8th edition) Cancer Staging Classification.

773 Background: Histological grade is a key prognostic factor in appendiceal adenocarcinomas (AAs) and has been incorporated in classification of stage IV AAs (IVA – Grade 1: Well; IVB – Grade 2/3: Moderately/Poorly differentiated) in AJCC Cancer Staging (8th edition). The purpose of the study was to corroborate the prognostic impact of this staging classifier. Methods: We performed a retrospective review of 98 AA patients (pts) at UTMDACC (2013 - 2017). Kaplan-Meier method was used to estimate median overall survival (mOS), compared with log-rank tests with emphasis on stage and grade. Results: The cohort included 18, 8, 14, 47 and 11 cases of stage II, III, IVA, IVB and IVC AAs. Histologically, 75 were mucinous (21 non mucinous) and 19, 35 and 42 were grade 1, 2 and 3 respectively. Median age of cohort was 54 years. Median follow-up was 46 months (m). The mOS of stage II, III, IVA, IVB and IVC was 136, 106, 140, 48, 23 m, respectively (P &lt; 0.0001). The mOS of grade 1, 2 and 3 was 160, 75 and 33 m, respectively (P &lt; 0.0001). In univariate analysis (restricted to stage IV pts), grade, AJCC stage, and cytoreductive surgery (CRS) were found to be associated with OS. In multivariate analyses (restricted to stage IV pts), only AJCC stage (HR 3.9, 95% CI: 1.5 - 10.6, P = 0.005) and CRS (HR 3.4, 95% CI: 1.4 – 8.3, P = 0.009) were found to be independently associated with poor OS. In subgroup of mucinous AAs, mOS of grade 3 (32 m) was significantly shorter than grade 2 (54 m) (P = 0.02). In non-mucinous AAs, mOS of grade 3 and grade 2 pts was 38 and 29 m, respectively (P = 0.97). Conclusions: AJCC staging classification has a strong prognostic value in AAs. Beyond the well differentiated AAs which are regarded as a distinct entity in stage IV disease, moderate and poor differentiation also has strong and dissimilar prognostic impact which appears to be dependent on mucinous or non-mucinous subtype in stage IV AAs. Further efforts are needed to incorporate the complex interplay of all grades and mucinous characteristics within the staging system for better prognostication and management.