Impact Of Susceptibility Research Articles

Association between plasma angiotensinogen level and response to valsartan among sample of Iraqi hypertensive patients.

Aim: The main aim of the present paper is to investigate allele frequencies of rs1799983 polymorphism eNOS genes and to determine association between rs1799983 polymorphism of eNOS gene and essential hypertension in Iraqi hypertensive patients. Materials and Methods: Data obtained at the Al-Diwaniyah teaching hospital in Iraq by researchers from the Department of Pharmacology and Therapeutics in the College of Medicine at University of Al-Qadisiyah from July 2022 to July 2023. All participants (aged 20 to 70) had been taking valsartan 160 mg once day for essential hypertension for at least two weeks before to the study. There were a total of 90 participants, 37 males and 53 women. Initial investigations of hypertension have indicated that the angiotensinogen gene has a substantial impact in susceptibility to essential hypertension through observational cross sectional descriptive single center study. Results: Indicate, in patients with essential hypertension, that the "AGT gene A>G (rs699) and C>T(rs5051)" have high angiotensinogen level, and there is no signif i cant association between these two (rs699, rs5051) and responsiveness to valsartan (P >0.05). Conclusions: Result showed the most common allele for rs699 was G allele (67%) while the most frequent genotype was AG (49%) and regarding rs5051 the most frequent allele was C (54%) while the most frequent genotype was CT (46%). In this study we demonstrate the lack of signif i cant association between two these polymorphisms and clinical response to valsartan (P >0.05).

Interaction Between Genetic Susceptibility and COVID-19 Pathogenesis in Pediatric Multisystem Inflammatory Disorders: The Role of Immune Responses.

Numerous studies have highlighted the emergence of coronavirus disease (COVID-19) symptoms reminiscent of Kawasaki disease in children, including fever, heightened multisystem inflammation, and multiorgan involvement, posing a life-threatening complication. Consequently, extensive research endeavors in pediatric have aimed to elucidate the intricate relationship between COVID-19 infection and the immune system. COVID-19 profoundly impacts immune cells, culminating in a cytokine storm that particularly inflicts damage on the pulmonary system. The gravity and vulnerability to COVID-19 are closely intertwined with the vigor of the immune response. In this context, the human leukocyte antigen (HLA) molecule assumes pivotal significance in shaping immune responses. Genetic scrutiny of HLA has unveiled the presence of at least one deleterious allele in children afflicted with multisystem inflammatory syndrome in children (MIS-C). Furthermore, research has demonstrated that COVID-19 exploits the angiotensin-converting enzyme 2 (ACE-2) receptor, transmembrane serine protease type 2, and various other genes to gain entry into host cells, with individuals harboring ACE-2 polymorphisms being at higher risk. Pediatric studies have employed diverse genetic methodologies, such as genome-wide association studies (GWAS) and whole exome sequencing, to scrutinize target genes. These investigations have pinpointed two specific genomic loci linked to the severity and susceptibility of COVID-19, with the HLA locus emerging as a notable risk factor. In this comprehensive review article, we endeavor to assess the available evidence and consolidate data, offering insights into current clinical practices and delineating avenues for future research. Our objective is to advance early diagnosis, stabilization, and appropriate management strategies to mitigate genetic susceptibility's impact on the incidence of COVID-19 in pediatric patients with multisystem inflammation.

Impact of Susceptibility on Plant Hormonal Composition during Clubroot Disease Development in Canola (Brassica napus).

Clubroot, caused by Plasmodiophora brassicae, is a soilborne disease of crucifers associated with the formation of large root galls. This root enlargement suggests modulation of plant hormonal networks by the pathogen, stimulating cell division and elongation and influencing host defense. We studied physiological changes in two Brassica napus cultivars, including plant hormone profiles-salicylic acid (SA), jasmonic acid (JA), abscisic acid (ABA), the auxin indole-3-acetic acid (IAA), and the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC)-along with their selected derivatives following inoculation with virulent and avirulent P. brassicae pathotypes. In susceptible plants, water uptake declined from the initial appearance of root galls by 21 days after inoculation, but did not have a significant effect on photosynthetic rate, stomatal conductance, or leaf chlorophyll levels. Nonetheless, a strong increase in ABA levels indicated that hormonal mechanisms were triggered to cope with water stress due to the declining water uptake. The free SA level in the roots increased strongly in resistant interactions, compared with a relatively minor increase during susceptible interactions. The ratio of conjugated SA to free SA was higher in susceptible interactions, indicating that resistant interactions are linked to the plant's ability to maintain higher levels of bioactive free SA. In contrast, JA and its biologically active form JA-Ile declined up to 7-fold in susceptible interactions, while they were maintained during resistant interactions. The ACC level increased in the roots of inoculated plants by 21 days, irrespective of clubroot susceptibility, indicating a role of ethylene in response to pathogen interactions that is independent of disease severity. IAA levels at early and later infection stages were lower only in susceptible plants, suggesting a modulation of auxin homeostasis by the pathogen relative to the host defense system.

Impact and a Novel Representation of Spatial Data Uncertainty in Debris Flow Susceptibility Analysis

In a study of debris flow susceptibility on the European continent, an analysis of the impact between known location and a location accuracy offset for 99 debris flows demonstrates the impact of uncertainty in defining appropriate predisposing factors and consequent analysis for areas of susceptibility. The dominant predisposing environmental factors, as determined through Maximum Entropy modeling, are presented and analyzed with respect to the values found at debris flow event points versus a buffered distance of locational uncertainty around each point. Maximum Entropy susceptibility models are developed utilizing the original debris flow inventory of points, randomly generated points, and two models utilizing a subset of points with an uncertainty of 5 km, 1 km, and a model utilizing only points with a known location of “exact”. The AUCs are 0.891, 0.893, 0.896, 0.921, and 0.93, respectively. The “exact” model, with the highest AUC, is ignored in final analyses due to the small number of points and localized distribution, and hence susceptibility results are likely non-representational of the continent. Each model is analyzed with respect to the AUC, highest contributing factors, factor classes, susceptibility impact, and comparisons of the susceptibility distributions and susceptibility value differences. Based on model comparisons, geographic extent, and the context of this study, the models utilizing points with a location uncertainty of less than or equal to 5 km best represent debris flow susceptibility for the continent of Europe. A novel representation of the uncertainty is expressed and included in a final susceptibility map, as an overlay of standard deviation and mean of susceptibility values for the two best models, providing additional insight for subsequent action.

Impact of Susceptibility of Interpersonal Influence, and Vanity Aspects on Luxury Brand Consumption

The present study has demonstrated the impact of consumer’s susceptibility of interpersonal influence and vanity aspects on luxury brand consumption. Study was conducted in the northwestern region of India with 650 research participants; quota sampling was used in the process of research. Researchers used SPSS 21.0 to explore reliability, factorability, and correlation among the variables. For analyzing the structural model, AMOS 21.0 was used. Results found that value-expressive influence affects luxury brand consumption more than utilitarian influence, and informational influence is positively related to luxury brand consumption. Results found that luxury brand consumption is associated with achievement aspects of luxury.

Consequences of Depletion of Susceptibles for Hazard Ratio Estimators Based on Propensity Scores

We use simulated data to examine the consequences of depletion of susceptibles for hazard ratio (HR) estimators based on a propensity score (PS). First, we show that the depletion of susceptibles attenuates marginal HRs toward the null by amounts that increase with the incidence of the outcome, the variance of susceptibility, and the impact of susceptibility on the outcome. If susceptibility is binary then the Bross bias multiplier, originally intended to quantify bias in a risk ratio from a binary confounder, also quantifies the ratio of the instantaneous marginal HR to the conditional HR as susceptibles are depleted differentially. Second, we show how HR estimates that are conditioned on a PS tend to be between the true conditional and marginal HRs, closer to the conditional HR if treatment status is strongly associated with susceptibility and closer to the marginal HR if treatment status is weakly associated with susceptibility. We show that associations of susceptibility with the PS matter to the marginal HR in the treated (ATT) though not to the marginal HR in the entire cohort (ATE). Third, we show how the PS can be updated periodically to reduce depletion-of-susceptibles bias in conditional estimators. Although marginal estimators can hit their ATE or ATT targets consistently without updating the PS, we show how their targets themselves can be misleading as they are attenuated toward the null. Finally, we discuss implications for the interpretation of HRs and their relevance to underlying scientific and clinical questions. See video Abstract: http://links.lww.com/EDE/B727.

3289 The Role of Suggestibility in Alcohol Use and Misuse

OBJECTIVES/SPECIFIC AIMS: Suggestibility, defined as the inclination to accept and internalize messages, has not been assessed much in relation to alcohol use. Prior research has shown that suggestibility to social cues and peer influence may play a role in driving alcohol consumption. Our previous work has shown associations between suggestibility and alcohol consumption in social drinkers. This study aims to examine how suggestibility and social susceptibility are related to ideas alcohol consumption and consequences across the spectrum of alcohol use and misuse. We hypothesize that those with higher suggestibility and social susceptibility reports will also have higher alcohol consumption and consequences, and that the impact of susceptibility is lower in dependent compared to non-dependent drinkers. METHODS/STUDY POPULATION: Study participants enrolled in the NIAAA screening and assessment protocol (N=157) completed questionnaires on suggestibility and alcohol consumption, The Multidimensional Iowa Suggestibility Scale (MISS) is a 95-question self-report assessment of suggestibility which draws from subcategories of consumer suggestibility, perceivability, physiological suggestibility, physiological reactivity, and peer conformity. Alcohol measures included 90-day Timeline Followback interviews and the Alcohol Use Disorder Identification Test (AUDIT). Participants also underwent the Structured Clinical Interviews for DSM-IV or DSM-5 disorders, and were stratified into two groups: alcohol dependent (N = 86) and non-dependent (N=71). Median split by age was additionally used to explore age’s relationship with suggestibility and alcohol with the under 36 (N = 45) and over 36 (N = 26) non-dependent groups. RESULTS/ANTICIPATED RESULTS: Initial analyses showed marked differences between the dependent and non-dependent groups in the relationship between the MISS total score and AUDIT total score. The non-dependent group showed significant positive correlations between MISS and AUDIT scores (r = 0.460, p < 0.001), while the dependent group did not show any correlation between MISS and AUDIT scores. Further examination of these relationships in the nondependent group revealed that MISS scores were also significantly positively correlated with AUDIT subscores of consumption, harm, and dependence. Age was found to have a significant negative correlation with MISS score (r = −0.354, p < 0.01). To better understand the role of age, the sample was split based on the median age (36 yrs), and analyzed separately. Results indicated robust relationships between MISS score and AUDIT (r = 0.457, p < 0.01) in the younger age group. In addition, the younger age group also showed significant relationships between MISS score and 90-day TLFB measures of total drinks, days drinking, and heavy drinking days. DISCUSSION/SIGNIFICANCE OF IMPACT: In non-dependent individuals, there was a significant positive relationship between suggestibility and alcohol measures, and these effects were amplified in younger individuals. No relationship was found between suggestibility and alcohol measures in the alcohol dependent individuals. This may be related to a greater impact of social and external contextual cues in younger social drinkers compared to dependent drinkers where tolerance and craving may have greater impact on alcohol consumption. These findings have important implications for traits that may put individuals at risk for developing harmful patterns of alcohol use and misuse. Future analyses will aim to examine biobehavioral underpinnings of the relationship between suggestibility and alcohol consumption.

Multiple sclerosis: Association of gelatinase B/matrix metalloproteinase-9 with risk and clinical course the disease

BackgroundMultiple sclerosis (MS) is an autoimmune disease characterized by inflammation and axonal degeneration of the central nervous system and a leading cause of disability in young adults. The matrix metalloproteinases in general and specially gelatinase B/metalloproteinase-9 (MMP-9) plays a role in the pathogenesis of multiple sclerosis. ObjectiveTo investigate the presence of the MMP-9 −1562C/T polymorphism in a Portuguese population of MS patients and assess its impact in susceptibility and course of the disease. The relation of MMP-9 serum levels with the polymorphism and with clinical and therapeutic factors will also be assessed. MethodsOur study included 355 Caucasian individuals distributed as MS patients (n=169) and controls (n=186). Samples were genotyped for −1562C/T polymorphism by PCR-RFLP analysis. MMP-9 concentration in serum was analyzed using a commercially available enzyme-linked immunosorbent assay. ResultsA significant increase in T-allele frequency was found in female MS patients, but not in the total patient population. No association between the presence of the polymorphism and disease progression was found. MMP-9 serum concentrations were increased in patients, and although not influenced by the −1562C/T polymorphism, were modified by INF-beta therapy. ConclusionAlthough we did not find an association of this polymorphism with disease susceptibility or prognosis, MMP-9 appears to be a good therapeutic response marker for multiple sclerosis.

This Month in Gastroenterology

This Month in Gastroenterology

Role of the CDKN2A Locus in Patients With Multiple Primary Melanomas

We have studied a consecutive case series of patients with multiple primary melanoma (MPM) for the involvement of the melanoma susceptibility loci CDKN2A and CDK4. One hundred four MPM patients (81 patients with two primary melanomas, 14 with three, five with four, one with five, two with six, and one with seven) were included. Seven different CDKN2A germline mutations were identified in 17 patients (16.3%). In total, we identified 15 CDKN2A exon 2, one exon 1alpha missense mutation, and one exon 1beta frameshift mutation. The age of onset was significantly lower and the number of primary melanomas higher in patients with mutations. CDKN2A mutations were more frequent in patients with familial history of melanoma (35.5%) compared with patients without (8.2%), with a relative risk (RR) of 4.32 (95% CI, 1.76 to 10.64; P = .001), and in patients with more than two melanomas (39.1%) compared with patients with only two melanomas (10%) with an RR of 3.29 (95% CI, 1.7 to 6.3; P = .002). The A148T polymorphism was more frequent in patients with MPMs than in the control population (P = .05). A variant of uncertain significance, A127S, was also detected in one patient. No CDK4 mutations were identified, suggesting that it has a low impact in susceptibility to MPM. MPM patients are good candidates for CDKN2A mutational screening. These patients and some of their siblings should be included in a program of specific follow-up with total body photography and digital dermoscopy, which will result in the early detection of melanoma in this subset of high-risk patients and improve phenotypic characterization.