Search results for: immune disease
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4304

Search results for: immune disease

4184 Immuno-Modulatory Role of Weeds in Feeds of Cyprinus Carpio

Authors: Vipin Kumar Verma, Neeta Sehgal, Om Prakash

Abstract:

Cyprinus carpio has a wide spread occurrence in the lakes and rivers of Europe and Asia. Heavy losses in natural environment due to anthropogenic activities, including pollution as well as pathogenic diseases have landed this fish in IUCN red list of vulnerable species. The significance of a suitable diet in preserving the health status of fish is widely recognized. In present study, artificial feed supplemented with leaves of two weed plants, Eichhornia crassipes and Ricinus communis were evaluated for their role on the fish immune system. To achieve this objective fish were acclimatized to laboratory conditions (25 ± 1 °C; 12 L: 12D) for 10 days prior to start of experiment and divided into 4 groups: non-challenged (negative control= A), challenged [positive control (B) and experimental (C & D)]. Group A, B were fed with non-supplemented feed while group C & D were fed with feed supplemented with 5% Eichhornia crassipes and 5% Ricinus communis respectively. Supplemented feeds were evaluated for their effect on growth, health, immune system and disease resistance in fish when challenged with Vibrio harveyi. Fingerlings of C. carpio (weight, 2.0±0.5 g) were exposed with fresh overnight culture of V. harveyi through bath immunization (concentration 2 Χ 105) for 2 hours on 10 days interval for 40 days. The growth was monitored through increase in their relative weight. The rate of mortality due to bacterial infection as well as due to effect of feed was recorded accordingly. Immune response of fish was analyzed through differential leucocyte count, percentage phagocytosis and phagocytic index. The effect of V. harveyi on fish organs were examined through histo-pathological examination of internal organs like spleen, liver and kidney. The change in the immune response was also observed through gene expression analysis. The antioxidant potential of plant extracts was measured through DPPH and FRAP assay and amount of total phenols and flavonoids were calculates through biochemical analysis. The chemical composition of plant’s methanol extracts was determined by GC-MS analysis, which showed presence of various secondary metabolites and other compounds. Investigation revealed immuno-modulatory effect of plants, when supplemented with the artificial feed of fish.

Keywords: immuno-modulation, gc-ms, Cyprinus carpio, Eichhornia crassipes, Ricinus communis

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4183 Role of Direct Immunofluorescence in Diagnosing Vesiculobullous Lesions

Authors: Mitakshara Sharma, Sonal Sharma

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Vesiculobullous diseases are heterogeneous group of dermatological disorders with protean manifestations. The most important technique for the patients with vesiculobullous diseases is conventional histopathology and confirmatory tests like direct immunofluorescence (DIF) and indirect immunofluorescence (IIF). DIF has been used for decades to investigate pathophysiology and in the diagnosis. It detects molecules such as immunoglobulins and complement components. It is done on the perilesional skin. Diagnosis of DIF test depends on features like primary site of the immune deposits, class of immunoglobulin, number of immune deposits and deposition at other sites. The aim of the study is to correlate DIF with clinical and histopathological findings and to analyze the utility of DIF in the diagnosis of these disorders. It is a retrospective descriptive study conducted for 2 years from 2015 to 2017 in Department of Pathology, GTB Hospital on perilesional punch biopsies of vesiculobullous lesions. Biopsies were sent in Michael’s medium. The specimens were washed, frozen and incubated with fluorescein isothiocyanate (FITC) tagged antihuman antibodies IgA, IgG, IgM, C3 & F and were viewed under fluorescent microscope. Out of 401 skin biopsies submitted for DIF, 285 were vesiculobullous diseases, in which the most common was Pemphigus vulgaris (34%) followed by Bullous pemphigoid (21.5%), Dermatitis herpetiformis (16%), Pemphigus foliaceus (11.9%), Linear IgA disease (11.9%), Epidermolysisbullosa (2.39%) and Pemphigus herpetiformis (1.7%). We will be presenting the DIF findings in the all these vesiculobullous diseases. DIF in conjugation with histopathology gives the best diagnostic yield in these lesions. It also helps in the diagnosis whenever there is a clinical and histopathological overlap.

Keywords: antibodies, direct immunofluorescence, pemphigus, vesiculobullous

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4182 The Difference of Serum Tnf-α Levels between Patients Schizophrenic Male with Smoking and Healthy Control

Authors: Rona Hanani Simamora, Bahagia Loebis, M. Surya Husada

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Background: The exact cause of schizophrenia is not known, although several etiology theories have been proposed for the disease, including immune dysfunction or autoimmune mechanisms. Cytokines including Tnf-α has an important role in the pathophysiology of schizophrenia and the effects of pharmacological treatment with antipsychotics. Nicotine is widespread effects on the brain, immune system and cytokine levels. Smoking among schizophrenic patients could play a role in the altered cytokine profiles of schizophrenia such as Tnf-α. Aims: To determine differences of serum Tnf-α levels between schizophrenic patients with smoking in male and healthy control. Methods: This study was a comparative analytic study, divided into two groups: 1) group of male schizophrenic patients with smoking (n1=30) with inclusion criteria were patients who have been diagnosed schizophrenic based PPDGJ-III, 20-60 years old, male, smoking, chronic schizophrenic patients in the stable phase and willing to participate this study. Exclusion criteria were having other mental disorders and comorbidity with other medical illnesses. 2) healthy control group (n2=30) with inclusion criteria were 20-60 years old, male, smoking, willing to participate this study. Exclusion criteria were having mental disorder, a family history of psychiatric disorders, the other medical illnesses, a history of alcohol and other substances abuse (except caffeine and nicotine). Serum Tnf-α were analyzed using the Quantikine HS Human Tnf –α Immunoassay. Results: Serum Tnf-α level measure in patient schizophrenia male with smoking and compared with the healthy control subjects. Tnf-α levels were significantly higher in patients schizophrenic male with smoking (25,79±27,96) to healthy control subjects (2,74±2,19), by using the Mann Whitney U test showed a statistically significant difference was observed for serum Tnf-α level (p < 0,001). Conclusions: Schizophrenia is a highly heterogeneous disorder, and this study shows an increase Tnf-α as pro-inflammation cytokines in schizophrenics. These results suggest an immune abnormalities may be involved in the etiology and pathophysiology of schizophrenia.

Keywords: male, schizophrenic, smoking, Tnf Alpha

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4181 Level of Awareness of Genetic Counselling in Benue State Nigeria: Its Advocacy on the Inheritance of Sickle Cell Disease

Authors: Agi Sunday

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A descriptive analysis of reported cases of sickle cell disease and the level of awareness about genetic counselling in 30 hospitals were carried out. Additionally, 150 individuals between ages 16-45 were randomly selected for evaluation of genetic counselling awareness. The main tools for this study were questionnaires which were taken to hospitals, and individuals completed the others. The numbers of reported cases of sickle cell disease recorded in private, public and teaching hospitals were 14 and 57; 143 and 89; 272 and 57 for the periods of 1995-2000 and 2001-2005, respectively. A general informal genetic counselling took place mostly in the hospitals visited. 122 (86%) individuals had the knowledge of genetic disease and only 43 (30.3%) individuals have been exposed to genetic counselling. 64% of individuals agreed that genetic counselling would help in the prevention of genetic disease.

Keywords: sickle disease, genetic counseling, genetic testing, advocacy

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4180 Analyzing the Impact of Migration on HIV and AIDS Incidence Cases in Malaysia

Authors: Ofosuhene O. Apenteng, Noor Azina Ismail

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The human immunodeficiency virus (HIV) that causes acquired immune deficiency syndrome (AIDS) remains a global cause of morbidity and mortality. It has caused panic since its emergence. Relationships between migration and HIV/AIDS have become complex. In the absence of prospectively designed studies, dynamic mathematical models that take into account the migration movement which will give very useful information. We have explored the utility of mathematical models in understanding transmission dynamics of HIV and AIDS and in assessing the magnitude of how migration has impact on the disease. The model was calibrated to HIV and AIDS incidence data from Malaysia Ministry of Health from the period of 1986 to 2011 using Bayesian analysis with combination of Markov chain Monte Carlo method (MCMC) approach to estimate the model parameters. From the estimated parameters, the estimated basic reproduction number was 22.5812. The rate at which the susceptible individual moved to HIV compartment has the highest sensitivity value which is more significant as compared to the remaining parameters. Thus, the disease becomes unstable. This is a big concern and not good indicator from the public health point of view since the aim is to stabilize the epidemic at the disease-free equilibrium. However, these results suggest that the government as a policy maker should make further efforts to curb illegal activities performed by migrants. It is shown that our models reflect considerably the dynamic behavior of the HIV/AIDS epidemic in Malaysia and eventually could be used strategically for other countries.

Keywords: epidemic model, reproduction number, HIV, MCMC, parameter estimation

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4179 Oral Microbiota as a Novel Predictive Biomarker of Response To Immune Checkpoint Inhibitors in Advanced Non-small Cell Lung Cancer Patients

Authors: Francesco Pantano, Marta Fogolari, Michele Iuliani, Sonia Simonetti, Silvia Cavaliere, Marco Russano, Fabrizio Citarella, Bruno Vincenzi, Silvia Angeletti, Giuseppe Tonini

Abstract:

Background: Although immune checkpoint inhibitors (ICIs) have changed the treatment paradigm of non–small cell lung cancer (NSCLC), these drugs fail to elicit durable responses in the majority of NSCLC patients. The gut microbiota, able to regulate immune responsiveness, is emerging as a promising, modifiable target to improve ICIs response rates. Since the oral microbiome has been demonstrated to be the primary source of bacterial microbiota in the lungs, we investigated its composition as a potential predictive biomarker to identify and select patients who could benefit from immunotherapy. Methods: Thirty-five patients with stage IV squamous and non-squamous cell NSCLC eligible for an anti-PD-1/PD-L1 as monotherapy were enrolled. Saliva samples were collected from patients prior to the start of treatment, bacterial DNA was extracted using the QIAamp® DNA Microbiome Kit (QIAGEN) and the 16S rRNA gene was sequenced on a MiSeq sequencing instrument (Illumina). Results: NSCLC patients were dichotomized as “Responders” (partial or complete response) and “Non-Responders” (progressive disease), after 12 weeks of treatment, based on RECIST criteria. A prevalence of the phylum Candidatus Saccharibacteria was found in the 10 responders compared to non-responders (abundance 5% vs 1% respectively; p-value = 1.46 x 10-7; False Discovery Rate (FDR) = 1.02 x 10-6). Moreover, a higher prevalence of Saccharibacteria Genera Incertae Sedis genus (belonging to the Candidatus Saccharibacteria phylum) was observed in "responders" (p-value = 6.01 x 10-7 and FDR = 2.46 x 10-5). Finally, the patients who benefit from immunotherapy showed a significant abundance of TM7 Phylum Sp Oral Clone FR058 strain, member of Saccharibacteria Genera Incertae Sedis genus (p-value = 6.13 x 10-7 and FDR=7.66 x 10-5). Conclusions: These preliminary results showed a significant association between oral microbiota and ICIs response in NSCLC patients. In particular, the higher prevalence of Candidatus Saccharibacteria phylum and TM7 Phylum Sp Oral Clone FR058 strain in responders suggests their potential immunomodulatory role. The study is still ongoing and updated data will be presented at the congress.

Keywords: oral microbiota, immune checkpoint inhibitors, non-small cell lung cancer, predictive biomarker

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4178 Microbiome Role in Tumor Environment

Authors: Chro Kavian

Abstract:

The studies conducted show that cancer is a disease caused by populations of microbes, a notion gaining traction as the interaction between the human microbiome and the tumor microenvironment (TME) increasingly shows how environment and microbes dictate the progress and treatment of neoplastic diseases. A person’s human microbiome is defined as a collection of bacteria, fungi, viruses, and other microorganisms whose structure and composition influence biological processes like immune system modulation and nutrient metabolism, which, in turn, affect how susceptible a person is to neoplastic diseases, and response to different therapies. Recent reports demonstrated the influence specific microbiome bacterial populations have on the TME, thereby altering tumoral behaviors and the TME’s contributing factors that impact patients' lives. In addition, gut microbes and their SCFA products are important determinants of the inflammatory landscape of tumors and augment anti-tumor immunity, which can influence immunotherapy outcomes. Studies have also found that dysbiosis, or microbial imbalance, correlates with biological processes such as cancer progression, metastasis, and therapy resistance, leading scientists to explore the use of microbiome deficiencies as adjunctive approaches to chemotherapy and other, more traditional treatments. Nonetheless, mental health practitioners struggling to comprehend the existent gap between cancer patients with pronounced resolutive capabilities and the profound clinical impact Microbiome-targeted cancer therapy has been proven to possess.

Keywords: microbiome, cancer, tumor, immune system

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4177 Role of DatScan in the Diagnosis of Parkinson's Disease

Authors: Shraddha Gopal, Jayam Lazarus

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Aims: To study the referral practice and impact of DAT-scan in the diagnosis or exclusion of Parkinson’s disease. Settings and Designs: A retrospective study Materials and methods: A retrospective study of the results of 60 patients who were referred for a DAT scan over a period of 2 years from the Department of Neurology at Northern Lincolnshire and Goole NHS trust. The reason for DAT scan referral was noted under 5 categories against Parkinson’s disease; drug-induced Parkinson’s, essential tremors, diagnostic dilemma, not responding to Parkinson’s treatment, and others. We assessed the number of patients who were diagnosed with Parkinson’s disease against the number of patients in whom Parkinson’s disease was excluded or an alternative diagnosis was made. Statistical methods: Microsoft Excel was used for data collection and statistical analysis, Results: 30 of the 60 scans were performed to confirm the diagnosis of early Parkinson’s disease, 13 were done to differentiate essential tremors from Parkinsonism, 6 were performed to exclude drug-induced Parkinsonism, 5 were done to look for alternative diagnosis as the patients were not responding to anti-Parkinson medication and 6 indications were outside the recommended guidelines. 55% of cases were confirmed with a diagnosis of Parkinson’s disease. 43.33% had Parkinson’s disease excluded. 33 of the 60 scans showed bilateral abnormalities and confirmed the clinical diagnosis of Parkinson’s disease. Conclusion: DAT scan provides valuable information in confirming Parkinson’s disease in 55% of patients along with excluding the diagnosis in 43.33% of patients aiding an alternative diagnosis.

Keywords: DATSCAN, Parkinson's disease, diagnosis, essential tremors

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4176 Effect of Fatty Acids in Feed on Levels of Antibody Titers and CD4 and CD8 T-Lymphocyte against Newcastle Disease Virus of Vaccinated Broiler Chicken

Authors: Alaa A. Shamaun Al-Abboodi, Yunis A. A. Bapeer

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400 one-day-old male broiler chicks (Ross-308) randomly divided to 2 main groups, 1st main group (GA) was feeding basal diet with medium chain fatty acid (MCFA) at rate of 0.15% and divided to four subgroups, 3 subgroups vaccinated with different routes with Newcastle Disease Virus (NDV) and non-vaccinated group. The 2nd main group (GB) feeding basal diet without MCFA and divided the same as 1st main group. The parameters used in this study included: ND antibody titers at 1, 10, 21, 28, 35 and 42 days of age and values of CD4 and CD8 at 1, 20, 30 and 42 days of age. This experiment detected increase in ND antibodies titers in (G1, G2, G3) groups were fed on basal diet MCFA comparing to groups were fed without adding MCFA (G5, G6, G7) and control groups (G4, G8). The results of cellular immune response (CD4 and CD8) T-cells in broiler chicks indicated that there was obviously significant relationship between dietary Fatty Acid (FA) versus the diet without FA on the level of CD4 parameter, for the entire experimental period. The effect of different ages was statistically significant in creating different values of CD4 level, whereas the CD4 level decreases markedly with age. However, analyzing the data of different vaccination methods, oculonasal method of vaccination led to the highest value of CD4 compared with the oral, S/C and control groups. There were statistical differences in CD8 values due to supplementation of FA versus the basal diet and due to the effect of different age periods. As for the age effect, the CD8 value at 20 days of age was significantly higher than at 42 and 30 days.

Keywords: broiler, CD4 and CD8, fatty acids, Newcastle Disease

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4175 A Decrease in the Anxiety Levels of Participants with Autoimmune Disease: Efficacy of a Community-Based Educational Program

Authors: Jennifer Hunter, Francisco Ramirez, Neil A. Nedley, Thania Solorio, Christian Freed, Erica Kinjo

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People who have autoimmune disease are often at an increased risk for psychological disorders such as anxiety. Untreated psychological conditions can affect the development of disease and can affect one’s general quality of life. In this study, it was hypothesized that an educational community-based intervention would be useful in decreasing the anxiety levels of participants with autoimmune disease. Programs, 2-hours long each, were held weekly over a period of eight weeks. During every meeting, a 45-minute DVD presentation by a skilled physician was shown, a small group discussion was guided by trained facilitators, and weekly practical assignments were given to each participant. The focus of the program was to educate participants about healthy lifestyle behaviors such as exercise, nutrition, sleep hygiene, helpful thought patterns etc., and to provide a group environment in which each participant was supported. Participants were assessed pre-post program for anxiety using the Depression and Anxiety Assessment Test (registration TX 7-398-022), a validated mental health test based on DSM-5 criteria and demographics. Anxiety scores were classified according to the DSM-5 criteria into 4 categories: none (0-6), mild (7-10), moderate (11-19) or severe (20 or more). Out of the participants who participated in programs conducted in the manner explained above (n=431), the average age was 54.9 (SD 16.6) and 81.9% were female. At baseline, the mean group anxiety level was 9.4 (SD 5.4). Within the baseline group, anxiety levels were as follows: none (21.1%), mild (22.0%), moderate (27.1%) and severe (29.7%). After the program, mean group anxiety decreased to 4.7 (SD 4.0). Post-program anxiety levels were as follows: none (54.8%), mild (27.1%), moderate (12.5%), severe (5.6%). The decrease in overall anxiety levels was significant t(431)=19.3 p<.001, 95% CI [0.815, 1.041]. It was concluded that the eight-week intensive was beneficial in decreasing the anxiety levels of participants. A long-term follow-up study would be beneficial in determining how lasting such improvements are especially since autoimmune diseases are often chronic. Additionally, future studies that utilize a control group would aid in establishing whether the improvements seen are due to the use of this specific lifestyle-educational program.

Keywords: anxiety, auto-immune disease, community-based educational program, lifestyle

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4174 Inferring Influenza Epidemics in the Presence of Stratified Immunity

Authors: Hsiang-Yu Yuan, Marc Baguelin, Kin O. Kwok, Nimalan Arinaminpathy, Edwin Leeuwen, Steven Riley

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Traditional syndromic surveillance for influenza has substantial public health value in characterizing epidemics. Because the relationship between syndromic incidence and the true infection events can vary from one population to another and from one year to another, recent studies rely on combining serological test results with syndromic data from traditional surveillance into epidemic models to make inference on epidemiological processes of influenza. However, despite the widespread availability of serological data, epidemic models have thus far not explicitly represented antibody titre levels and their correspondence with immunity. Most studies use dichotomized data with a threshold (Typically, a titre of 1:40 was used) to define individuals as likely recently infected and likely immune and further estimate the cumulative incidence. Underestimation of Influenza attack rate could be resulted from the dichotomized data. In order to improve the use of serosurveillance data, here, a refinement of the concept of the stratified immunity within an epidemic model for influenza transmission was proposed, such that all individual antibody titre levels were enumerated explicitly and mapped onto a variable scale of susceptibility in different age groups. Haemagglutination inhibition titres from 523 individuals and 465 individuals during pre- and post-pandemic phase of the 2009 pandemic in Hong Kong were collected. The model was fitted to serological data in age-structured population using Bayesian framework and was able to reproduce key features of the epidemics. The effects of age-specific antibody boosting and protection were explored in greater detail. RB was defined to be the effective reproductive number in the presence of stratified immunity and its temporal dynamics was compared to the traditional epidemic model using use dichotomized seropositivity data. Deviance Information Criterion (DIC) was used to measure the fitness of the model to serological data with different mechanisms of the serological response. The results demonstrated that the differential antibody response with age was present (ΔDIC = -7.0). The age-specific mixing patterns with children specific transmissibility, rather than pre-existing immunity, was most likely to explain the high serological attack rates in children and low serological attack rates in elderly (ΔDIC = -38.5). Our results suggested that the disease dynamics and herd immunity of a population could be described more accurately for influenza when the distribution of immunity was explicitly represented, rather than relying only on the dichotomous states 'susceptible' and 'immune' defined by the threshold titre (1:40) (ΔDIC = -11.5). During the outbreak, RB declined slowly from 1.22[1.16-1.28] in the first four months after 1st May. RB dropped rapidly below to 1 during September and October, which was consistent to the observed epidemic peak time in the late September. One of the most important challenges for infectious disease control is to monitor disease transmissibility in real time with statistics such as the effective reproduction number. Once early estimates of antibody boosting and protection are obtained, disease dynamics can be reconstructed, which are valuable for infectious disease prevention and control.

Keywords: effective reproductive number, epidemic model, influenza epidemic dynamics, stratified immunity

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4173 NK Cells Expansion Model from PBMC Led to a Decrease of CD4+ and an Increase of CD8+ and CD25+CD127- T-Reg Lymphocytes in Patients with Ovarian Neoplasia

Authors: Rodrigo Fernandes da Silva, Daniela Maira Cardozo, Paulo Cesar Martins Alves, Sophie Françoise Derchain, Fernando Guimarães

Abstract:

T-reg lymphocytes are important for the control of peripheral tolerance. They control the adaptive immune system and prevent autoimmunity through its suppressive action on CD4+ and CD8+ lymphocytes. The suppressive action also includes B lymphocytes, dendritic cells, monocytes/macrophages and recently, studies have shown that T-reg are also able to inhibit NK cells, therefore they exert their control of the immune response from innate to adaptive response. Most tumors express self-ligands, therefore it is believed that T-reg cells induce tolerance of the immune system, hindering the development of successful immunotherapies. T-reg cells have been linked to the suppression mechanisms of the immune response against tumors, including ovarian cancer. The goal of this study was to disclose the sub-population of the expanded CD3+ lymphocytes reported by previous studies, using the long-term culture model designed by Carlens et al 2001, to generate effector cell suspensions enriched with cytotoxic CD3-CD56+ NK cells, from PBMC of ovarian neoplasia patients. Methods and Results: Blood was collected from 12 patients with ovarian neoplasia after signed consent: 7 benign (Bng) and 5 malignant (Mlg). Mononuclear cells were separated by Ficoll-Paque gradient. Long-term culture was conducted by a 21 day culturing process with SCGM CellGro medium supplemented with anti-CD3 (10ng/ml, first 5 days), IL-2 (1000UI/ml) and FBS (10%). After 21 days of expansion, there was an increase in the population of CD3+ lymphocytes in the benign and malignant group. Within CD3+ population, there was a significant decrease in the population of CD4+ lymphocytes in the benign (median Bgn D-0=73.68%, D-21=21.05%) (p<0.05) and malignant (median Mlg D-0=64.00%, D-21=11.97%) (p < 0.01) group. Inversely, after 21 days of expansion, there was an increase in the population of CD8+ lymphocytes within the CD3+ population in the benign (median Bgn D-0=16.80%, D-21=38.56%) and malignant (median Mlg D-0=27.12%, D-21=72.58%) group. However, this increase was only significant on the malignant group (p<0.01). Within the CD3+CD4+ population, there was a significant increase (p < 0.05) in the population of T-reg lymphocytes in the benign (median Bgn D-0=9.84%, D-21=39.47%) and malignant (median Mlg D-0=3.56%, D-21=16.18%) group. Statistical analysis inter groups was performed by Kruskal-Wallis test and intra groups by Mann Whitney test. Conclusion: The CD4+ and CD8+ sub-population of CD3+ lymphocytes shifts with the culturing process. This might be due to the process of the immune system to produce a cytotoxic response. At the same time, T-reg lymphocytes increased within the CD4+ population, suggesting a modulation of the immune response towards cells of the immune system. The expansion of the T-reg population can hinder an immune response against cancer. Therefore, an immunotherapy using this expansion procedure should aim to halt the expansion of T-reg or its immunosuppresion capability.

Keywords: regulatory T cells, CD8+ T cells, CD4+ T cells, NK cell expansion

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4172 Hepatocyte-Intrinsic NF-κB Signaling Is Essential to Control a Systemic Viral Infection

Authors: Sukumar Namineni, Tracy O'Connor, Ulrich Kalinke, Percy Knolle, Mathias Heikenwaelder

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The liver is one of the pivotal organs in vertebrate animals, serving a multitude of functions such as metabolism, detoxification and protein synthesis and including a predominant role in innate immunity. The innate immune mechanisms pertaining to liver in controlling viral infections have largely been attributed to the Kupffer cells, the locally resident macrophages. However, all the cells of liver are equipped with innate immune functions including, in particular, the hepatocytes. Hence, our aim in this study was to elucidate the innate immune contribution of hepatocytes in viral clearance using mice lacking Ikkβ specifically in the hepatocytes, termed IkkβΔᴴᵉᵖ mice. Blockade of Ikkβ activation in IkkβΔᴴᵉᵖ mice affects the downstream signaling of canonical NF-κB signaling by preventing the nuclear translocation of NF-κB, an important step required for the initiation of innate immune responses. Interestingly, infection of IkkβΔᴴᵉᵖ mice with lymphocytic choriomeningitis virus (LCMV) led to strongly increased hepatic viral titers – mainly confined in clusters of infected hepatocytes. This was due to reduced interferon stimulated gene (ISG) expression during the onset of infection and a reduced CD8+ T-cell-mediated response. Decreased ISG production correlated with increased liver LCMV protein and LCMV in isolated hepatocytes from IkkβΔᴴᵉᵖ mice. A similar phenotype was found in LCMV-infected mice lacking interferon signaling in hepatocytes (IFNARΔᴴᵉᵖ) suggesting a link between NFkB and interferon signaling in hepatocytes. We also observed a failure of interferon-mediated inhibition of HBV replication in HepaRG cells treated with NF-kB inhibitors corroborating our initial findings with LCMV infections. Collectively, these results clearly highlight a previously unknown and influential role of hepatocytes in the induction of innate immune responses leading to viral clearance during a systemic viral infection with LCMV-WE.

Keywords: CD8+ T cell responses, innate immune mechanisms in the liver, interferon signaling, interferon stimulated genes, NF-kB signaling, viral clearance

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4171 A C/T Polymorphism at the 5’ Untranslated Region of CD40 Gene in Patients Associated with Graves’ Disease in Kumaon Region

Authors: Sanjeev Kumar Shukla, Govind Singh, Prabhat Pant Shahzad Ahmad

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Background: Graves’ disease is an autoimmune disorder with a genetic predisposition, and CD40 plays a pathogenic role in various autoimmune diseases. A single nucleotide polymorphism at position –1 of the Kozak sequence of the 5 untranslated regions of the CD40 gene of exon 1 has been reported to be associated with the development of Graves’ Disease. Objective: The aim of the present study was to investigate whether CD40 gene polymorphism confers susceptibility to Graves’ disease in the Kumaon region. CD40 gene polymorphisms were studied in Graves’ Disease patients (n=50) and healthy control subjects without anti-thyroid autoantibodies or a family history of autoimmune disorders (n=50). Material and Method: CD40 gene polymorphisms were studied in fifty Graves’ Disease patients and fifty healthy control subjects. All samples were collected from STG Hospital, Haldwani, Nainital. A C/T polymorphism at position –1 of the CD40 gene was measured using the polymerase chain reaction-restriction fragment length polymorphism. Results: There was no significant difference in allele or genotype frequency of the CD40 SNP between Graves’ Disease and control subjects. There was a significant decrease in the TT genotype frequency in the Graves’ Disease patients who developed Graves’ Disease after 40 years old than those under 40 years of age. These data suggest that the SNP of the CD40 gene is associated with susceptibility to the later onset of Graves’ Disease. Conclusion: The CD40 gene was a different susceptibility gene for Graves’ Disease within certain families because it was both linked and associated with Graves’ Disease.

Keywords: autoimmune diseases, pathogenesis, diagnosis, therapy

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4170 Immune Modulation and Cytomegalovirus Reactivation in Sepsis-Induced Immunosuppression

Authors: G. Lambe, D. Mansukhani, A. Shetty, S. Khodaiji, C. Rodrigues, F. Kapadia

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Introduction: Sepsis is known to cause impairment of both innate and adaptive immunity and involves an early uncontrolled inflammatory response, followed by a protracting immunosuppression phase, which includes decreased expression of cell receptors, T cell anergy and exhaustion, impaired cytokine production, which may cause high risk for secondary infections due to reduced response to antigens. Although human cytomegalovirus (CMV) is widely recognized as a serious viral pathogen in sepsis and immunocompromised patients, the incidence of CMV reactivation in patients with sepsis lacking strong evidence of immunosuppression is not well defined. Therefore, it is important to determine an association between CMV reactivation and sepsis-induced immunosuppression. Aim: To determine the association between incidence of CMV reactivation and immune modulation in sepsis-induced immunosuppression with time. Material and Methods: Ten CMV-seropositive adult patients with severe sepsis were included in this study. Blood samples were collected on Day 0, and further weekly up to 21 days. CMV load was quantified by real-time PCR using plasma. The expression of immunosuppression markers, namely, HLA-DR, PD-1, and regulatory T cells, were determined by flow cytometry using whole blood. Results: At Day 0, no CMV reactivation was observed in 6/10 patients. In these patients, the median length for reactivation was 14 days (range, 7-14 days). The remaining four patients, at Day 0, had a mean viral load of 1802+2599 copies/ml, which increased with time. At Day 21, the mean viral load for all 10 patients was 60949+179700 copies/ml, indicating that viremia increased with the length of stay in the hospital. HLA-DR expression on monocytes significantly increased from Day 0 to Day 7 (p = 0.001), following which no significant change was observed until Day 21, for all patients except 3. In these three patients, HLA-DR expression on monocytes showed a decrease at elevated viral load (>5000 copies/ml), indicating immune suppression. However, the other markers, PD-1 and regulatory T cells, did not show any significant changes. Conclusion: These preliminary findings suggest that CMV reactivation can occur in patients with severe sepsis. In fact, the viral load continued to increase with the length of stay in the hospital. Immune suppression, indicated by decreased expression of HLA-DR alone, was observed in three patients with elevated viral load.

Keywords: CMV reactivation, immune suppression, sepsis immune modulation, CMV viral load

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4169 Th2 and Th17 Subsets in the Circulation of Psoriasis Patients

Authors: Chakrit Thapphan, Suteeraporn Chaowattanapanit, Sorutsiri Chareonsudjai, Wisitsak Phoksawat, Supranee Phantanawiboon, Kiatichai Faksri, Steve W. Edwards, Kanin Salao

Abstract:

Background: Psoriasis is a chronic inflammatory disease of the skin that is mediated by crosstalk between keratinocytes and immune cells, especially CD4+ T helper (Th) cells. To date, psoriasis is established as a T helper 17 (Th17) cell-mediated inflammatory process driven by the over-expression of Th17. However, the role of other CD4+T helper cells is rather controversial. Objective: Our study, thereby, aimed to characterize and analyze T cell subsets in the circulating blood of psoriasis patients and compare them to healthy controls. Methods: Peripheral blood mononuclear cells were isolated from the participants and stained with fluorescent dye-conjugated monoclonal antibodies specific for intracellular cytokines, including interferon-gamma (IFN- γ), interleukin (IL-4), IL-17 and forkhead box P3 (FOXP3), that can be used to define T helper 1 (Th1) cells, T helper 2 (Th2), T helper 17 (Th17) and regulatory T cells (Treg) respectively. Results: We found that the numbers of Th2 (59.6% ± 17.0) and Th17 (4.0% ± 2.0) cells in the circulating blood of psoriasis patients were significantly higher than those of the healthy controls (p= 0.0007 and 0.0013 respectively). In contrast, the numbers of Th1 and Treg cells were not significantly different between psoriasis patients and healthy controls (p= 0.0593 and 0.8518, respectively). Additionally, when adjusting these numbers of Th cells to Treg, we observed a similar trend that the ratio of Th2/Treg and Th17/Treg also elevated (p = 0.0007 and 0.0047, respectively). Conclusion: Taken together, our results suggest an imbalanced T exhibit toward the Th2 and Th17 skewed-immune responses in psoriasis patients.

Keywords: psoriasis, Th cell subsets, Th2 cells, Th17 cells, Treg cells

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4168 Human Endogenous Retrovirus Link With Multiple Sclerosis Disease Progression

Authors: Sina Mahdavi

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Background and Objective: Multiple sclerosis (MS) is an inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially human endogenous retrovirus (HERV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on HERV infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis", "Human endogenous retrovirus", and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched and 14 articles chosen, studied, and analyzed. Results: In the leptomeningeal cells of MS patients, a retrovirus-like element associated with reverse transcriptase (RT) activity called multiple sclerosis-associated retroviruses (MSRV) has been identified. HERVs are expressed in the human CNS despite mechanisms to suppress their expression. External factors, especially viral infections such as influenza virus, Epstein-Barr virus, and herpes simplex virus type 1, can activate HERV gene expression. The MSRV coat protein is activated by activating TLR4 at the brain surface, particularly in oligodendroglial progenitor cells and macrophages, leading to immune cascades followed by the downregulation of myelin protein expression. The HERV-K18 envelope gene (env) acts as a superantigen and induces inflammatory responses in patients with MS. Conclusion: There is a high expression of endogenous retroviruses during the course of MS, which indicates the relationship between HERV and MS, that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of endogenous retroviruses may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, human endogenous retrovirus, central nervous system, MSRV

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4167 Prevalence Of Periodontal Disease In Felines In The Outskirts Of The City Of Manaus, Brazil: An Epidemiological Study

Authors: Pármenas Costa Macedo do Nascimento

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Periodontal disease is the most common disease in the oral cavity of felines. It starts with the accumulation of bacteria on the tooth surface supporting the tissues of the periodontal tissue, namely gums, alveolar bone, cementum, and periodontal ligament. The main clinical symptom observed by the owner is bad breath, which may lead to local and systemic consequences depending on the stage of periodontal disease, such as bleeding and bone loss. Therefore, the study is important to educate tutors to take better care of the felines oral health in order to try to prevent the disease. For this epidemiological study, the target population has been felines, located on the outskirts of Manaus, in the state of Amazonas, with a geographic area of 155.68 km², with no defined breed, from October 1st to 10th, 2021, whose samples has been randomly selected, with a detailed profile. The variables of interest for this study have been: absence or presence of periodontal disease, gender, age (delimited by age group), and condition (domiciled or homeless). Using a sample of 40 felines from 4 districts of the east side of Manaus chosen at random, an oral exam has been made to identify the studied disease. The animal's apparent age, condition, sex, and presence or absence of periodontal disease has been noted. It has been observed that 70% (28/40) of them had periodontal disease, mostly females, aged between 0 and 5 years and domiciled, totaling 30% (12/40).

Keywords: felines, oral cavity, oral exam, periodontal disease

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4166 Cutaneous Crohn’s Disease in a Child: Atypical Axillary Involvement

Authors: A. Al Yousef, A. Toulon, L. Petit, S. Fraitag, F. Ruemmele, S. Hadj-Rabia, C. Bodemer

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Cutaneous Crohn’s disease (CCD) refers to an extremely rare granulomatous inflammation of the skin that is non-contiguous to the bowel tract. These cutaneous lesions can occur prior to, concurrent with, or after the gastrointestinal manifestations. In adults, CCD most frequently occurs in the setting of well-documented intestinal disease. Only 20% of cases occur prior to its development. Review of CCD in children, reveals that 86% of cases (24 of 28) occurring in patients without a known diagnosis of intestinal Crohn’s disease. Overall, the genitalia was the most commonly involved location, representing 21 of the 28 cases with 16 vulvar and 5 penile/scrotal lesions.

Keywords: Crohn’s disease, cutaneous manifestations, children, atypical axillary involvement

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4165 Expression of Gro-El under Phloem-Specific Promoter Protects Transgenic Plants against Diverse Begomovirus-Beta Satellite Complex

Authors: Muhammad Yousaf Ali, Shahid Mansoor, Javeria Qazi, Imran Amin, Musarrat Shaheen

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Cotton leaf curl disease (CLCuD) is the major threat to the cotton crop and is transmitted by whitefly (Bemisia tabaci). Since multiple begomoviruses and associated satellites are involved in CLCuD, approaches based on the concept of broad-spectrum resistance are essential for effective disease control. Gro-El and G5 are two proteins from whitefly endosymbiont and M13 bacteriophage origin, respectively. Gro-El encapsulates the virus particle when it enters the whitefly and protects the virus from the immune system of the whitefly as well as prevents viral expression in it. This characteristic of Gro-El can be exploited to get resistance against viruses if expressed in plants. G5 is a single-stranded DNA binding protein, expression of which in transgenic plants will stop viral expression on its binding with ssDNA. The use of tissue-specific promoters is more efficient than constitutive promoters. Transgenics of Nicotiana benthamiana for Gro-El under constitutive promoter and Gro-El under phloem specific promoter were made. In comparison to non-transgenic plants, transgenic plants with Gro-El under NSP promoter showed promising results when challenged against cotton leaf curl Multan virus (CLCuMuV) along with cotton leaf curl Multan beta satellite (CLCuMB), cotton leaf curl Khokhran virus (CLCuKoV) along with cotton leaf curl Multan beta satellite (CLCuMB) and Pedilenthus leaf curl virus (PedLCV) along with Tobacco leaf curl beta satellite (TbLCB).

Keywords: cotton leaf curl disease, whitefly, endosymbionts, transgenic, resistance

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4164 Role of Toll Like Receptor-2 in Female Genital Tuberculosis Disease Infection and Its Severity

Authors: Swati Gautam, Salman Akhtar, S. P. Jaiswar, Amita Jain

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Background: FGTB is now a major global health problem mostly in developing countries including India. In humans, Mycobacterium Tuberculosis (M.tb) is a causating agent of infection. High index of suspicion is required for early diagnosis due to asymptomatic presentation of FGTB disease. In macrophages Toll Like Receptor-2 (TLR-2) is one which mediated host’s immune response to M.tb. The expression of TLR-2 on macrophages is important to determine the fate of innate immune responses to M.tb. TLR-2 have two work. First its high expression on macrophages worsen the outer of infection and another side, it maintains M.tb to its dormant stage avoids activation of M.tb from latent phase. Single Nucleotide Polymorphism (SNP) of TLR-2 gene plays an important role in susceptibility to TB among different populations and subsequently, in the development of infertility. Methodology: This Case-Control study was done in the Department of Obs and Gynae and Department of Microbiology at King George’s Medical University, U.P, Lucknow, India. Total 300 subjects (150 Cases and 150 Controls) were enrolled in the study. All subjects were enrolled only after fulfilling the given inclusion and exclusion criteria. Inclusion criteria: Age 20-35 years, menstrual-irregularities, positive on Acid-Fast Bacilli (AFB), TB-PCR, (LJ/MGIT) culture in Endometrial Aspiration (EA). Exclusion criteria: Koch’s active, on ATT, PCOS, and Endometriosis fibroid women, positive on Gonococal and Chlamydia. Blood samples were collected in EDTA tubes from cases and healthy control women (HCW) and genomic DNA extraction was carried out by salting-out method. Genotyping of TLR2 genetic variants (Arg753Gln and Arg677Trp) were performed by using single amplification refractory mutation system (ARMS) PCR technique. PCR products were analyzed by electrophoresis on 1.2% agarose gel and visualized by gel-doc. Statistical analysis of the data was performed using the SPSS 16.3 software and computing odds ratio (OR) with 95% CI. Linkage Disequiliribium (LD) analysis was done by SNP stats online software. Results: In TLR-2 (Arg753Gln) polymorphism significant risk of FGTB observed with GG homozygous mutant genotype (OR=13, CI=0.71-237.7, p=0.05), AG heterozygous mutant genotype (OR=13.7, CI=0.76-248.06, p=0.03) however, G allele (OR=1.09, CI=0.78-1.52, p=0.67) individually was not associated with FGTB. In TLR-2 (Arg677Trp) polymorphism a significant risk of FGTB observed with TT homozygous mutant genotype (OR= 0.020, CI=0.001-0.341, p < 0.001), CT heterozygous mutant genotype (OR=0.53, CI=0.33-0.86, p=0.014) and T allele (OR=0.463, CI=0.32-0.66, p < 0.001). TT mutant genotype was only found in FGTB cases and frequency of CT heterozygous more in control group as compared to FGTB group. So, CT genotype worked as protective mutation for FGTB susceptibility group. In haplotype analysis of TLR-2 genetic variants, four possible combinations, i.e. (G-T, A-C, G-C, and A-T) were obtained. The frequency of haplotype A-C was significantly higher in FGTB cases (0.32). Control group did not show A-C haplotype and only found in FGTB cases. Conclusion: In conclusion, study showed a significant association with both genetic variants of TLR-2 of FGTB disease. Moreover, the presence of specific associated genotype/alleles suggest the possibility of disease severity and clinical approach aimed to prevent extensive damage by disease and also helpful for early detection of disease.

Keywords: ARMS, EDTA, FGTB, TLR

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4163 No-Fee Shot for Life: Immune Defense from Covid-19, Acute Debilitation and Untimely Death through Vaccinations for Ages 60 and Above, Protection of the Elderly and Seniors

Authors: Maeah Stephanie A. Macapaz Abadejos

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Covid-19 shook the whole world. Every person on all sides of the world was affected by the pandemic. All the nations and world leaders were searching for a variety of cures and solutions to stop the spread of the virus. In connection with this, this investigative case study aims to show a relationship between COVID-19 vaccinations to the immune system of the seniors and elderly. The seniors and elderly are one of the most vulnerable populations that show high morbidity and mortality in any illnesses and diseases. This study will show lived experiences of the senior’s immune system and health status, how it is being affected by the COVID-19 virus and its vaccines, Risk for COVID-19 Infection, Hospitalization, and Death by Age Group. Participants of this study are from 3 Cebu City Barangays and 2 from Barangays of the Cities of the Cebu Province. To conclude, this study shall serve its purpose of providing clear and concise results in strengthening the evidence of the effects of the COVID-19 virus infection, especially the free vaccinations, on the health and overall well-being of the elderly and seniors.

Keywords: gerontology nursing, vaccination, protection and immunity, seniors and the elderly

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4162 Management of Coronary Heart Disease through Yoga

Authors: Subramaniam Iyer

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The most common disease that is pertaining to all human beings is heart-related. The reasons for coronary artery disease are due to lifestyle and eating habits. Due to this, many people mentally become sick, feeling that soon they will die due to their heart problems. This results in stress and anxiety, which has become common amongst all the Indians. Medicines are the commonest curative remedy in India, but it is proposed through this article some remedies through yoga. This article does not guarantee a 100% result, but it is a preventive remedy for coronary artery disease. Yoga is giving a new lease of life to many, so to tackle chronic diseases, it provides remedies that will be lifelong. It is brought to many people by Patanjali. Yoga will provide support to patients having coronary artery disease through its various relevant postures (asanas), which can be done very easily. Yoga does not send a message that if you do it regularly, you will be relieved from a particular disease. If it is performed every day, it will add vital energy for a smooth life, even if you are suffering from any chronic disease. In this article, we will be providing 6 postures (asanas), which can be performed at any time in the day, but the early morning will always be preferred (empty stomach) to get a good result. Secondly, these postures must be implemented after due consultation with your physician. If your physician disapproves, don’t do these postures as it will be harmful to your body.

Keywords: coronary artery, yoga, disease, remedy, medicine

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4161 Developing a Deep Understanding of the Immune Response in Hepatitis B Virus Infected Patients Using a Knowledge Driven Approach

Authors: Hanan Begali, Shahi Dost, Annett Ziegler, Markus Cornberg, Maria-Esther Vidal, Anke R. M. Kraft

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Chronic hepatitis B virus (HBV) infection can be treated with nucleot(s)ide analog (NA), for example, which inhibits HBV replication. However, they have hardly any influence on the functional cure of HBV, which is defined by hepatitis B surface antigen (HBsAg) loss. NA needs to be taken life-long, which is not available for all patients worldwide. Additionally, NA-treated patients are still at risk of developing cirrhosis, liver failure, or hepatocellular carcinoma (HCC). Although each patient has the same components of the immune system, immune responses vary between patients. Therefore, a deeper understanding of the immune response against HBV in different patients is necessary to understand the parameters leading to HBV cure and to use this knowledge to optimize HBV therapies. This requires seamless integration of an enormous amount of diverse and fine-grained data from viral markers, e.g., hepatitis B core-related antigen (HBcrAg) and hepatitis B surface antigen (HBsAg). The data integration system relies on the assumption that profiling human immune systems requires the analysis of various variables (e.g., demographic data, treatments, pre-existing conditions, immune cell response, or HLA-typing) rather than only one. However, the values of these variables are collected independently. They are presented in a myriad of formats, e.g., excel files, textual descriptions, lab book notes, and images of flow cytometry dot plots. Additionally, patients can be identified differently in these analyses. This heterogeneity complicates the integration of variables, as data management techniques are needed to create a unified view in which individual formats and identifiers are transparent when profiling the human immune systems. The proposed study (HBsRE) aims at integrating heterogeneous data sets of 87 chronically HBV-infected patients, e.g., clinical data, immune cell response, and HLA-typing, with knowledge encoded in biomedical ontologies and open-source databases into a knowledge-driven framework. This new technique enables us to harmonize and standardize heterogeneous datasets in the defined modeling of the data integration system, which will be evaluated in the knowledge graph (KG). KGs are data structures that represent the knowledge and data as factual statements using a graph data model. Finally, the analytic data model will be applied on top of KG in order to develop a deeper understanding of the immune profiles among various patients and to evaluate factors playing a role in a holistic profile of patients with HBsAg level loss. Additionally, our objective is to utilize this unified approach to stratify patients for new effective treatments. This study is developed in the context of the project “Transforming big data into knowledge: for deep immune profiling in vaccination, infectious diseases, and transplantation (ImProVIT)”, which is a multidisciplinary team composed of computer scientists, infection biologists, and immunologists.

Keywords: chronic hepatitis B infection, immune response, knowledge graphs, ontology

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4160 Trichoderma spp Consortium and Its Efficacy as Biological Control Agent of Ganoderma Disease of Oil Palm (Elaies guineensis Jacquin)

Authors: Habu Musa, Nusaibah Binti Syd Ali

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Oil palm industries particularly in Malaysia and Indonesia are being devastated by Ganoderma disease caused by Ganoderma spp. To date, this disease has been causing serious oil palm yield losses and collapse of oil palm trees, thus affecting its contribution to the producer’s economy. Research on sustainable and eco-friendly remedy to counter Ganoderma disease is on the upsurge to avoid the current control measures via synthetic fungicides. Trichoderma species have been the most studied and valued microbes as biological control agents in an effort to combat a wide range of plant diseases sustainably. Therefore, in this current study, the potential of Trichoderma spp. (Trichoderma asperellum, Trichoderma harzianum, and Trichoderma virens) as a consortium approach was evaluated as biological control agents against Ganoderma disease on oil palm. The consortium of Trichoderma spp. applied found to be the most effective treatment in suppressing Ganoderma disease with 83.03% and 89.16% from the foliar and bole symptoms respectively. Besides, it exhibited tremendous enhancement in the oil palm seedling vegetative growth parameters. Also, it had highly induced significant activity of peroxidase, polyphenol oxidase and total phenolic content was recorded in the consortium treatment compared to the control treatment. Disease development was slower in the seedlings treated with consortium of Trichoderma spp. compared to the positive control, which exhibited with the highest percentage of disease severity.

Keywords: biological control, ganoderma disease, trichoderma, disease severity

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4159 Immuno-Protective Role of Mucosal Delivery of Lactococcus lactis Expressing Functionally Active JlpA Protein on Campylobacter jejuni Colonization in Chickens

Authors: Ankita Singh, Chandan Gorain, Amirul I. Mallick

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Successful adherence of the mucosal epithelial cells is the key early step for Campylobacter jejuni pathogenesis (C. jejuni). A set of Surface Exposed Colonization Proteins (SECPs) are among the major factors involved in host cell adherence and invasion of C. jejuni. Among them, constitutively expressed surface-exposed lipoprotein adhesin of C. jejuni, JlpA, interacts with intestinal heat shock protein 90 (hsp90α) and contributes in disease progression by triggering pro-inflammatory response via activation of NF-κB and p38 MAP kinase pathway. Together with its ability to express in the bacterial surface, higher sequence conservation and predicted predominance of several B cells epitopes, JlpA protein reserves its potential to become an effective vaccine candidate against wide range of Campylobacter sps including C. jejuni. Given that chickens are the primary sources for C. jejuni and persistent gut colonization remain as major cause for foodborne pathogenesis to humans, present study explicitly used chickens as model to test the immune-protective efficacy of JlpA protein. Taking into account that gastrointestinal tract is the focal site for C. jejuni colonization, to extrapolate the benefit of mucosal (intragastric) delivery of JlpA protein, a food grade Nisin inducible Lactic acid producing bacteria, Lactococcus lactis (L. lactis) was engineered to express recombinant JlpA protein (rJlpA) in the surface of the bacteria. Following evaluation of optimal surface expression and functionality of recombinant JlpA protein expressed by recombinant L. lactis (rL. lactis), the immune-protective role of intragastric administration of live rL. lactis was assessed in commercial broiler chickens. In addition to the significant elevation of antigen specific mucosal immune responses in the intestine of chickens that received three doses of rL. lactis, marked upregulation of Toll-like receptor 2 (TLR2) gene expression in association with mixed pro-inflammatory responses (both Th1 and Th17 type) was observed. Furthermore, intragastric delivery of rJlpA expressed by rL. lactis, but not the injectable form, resulted in a significant reduction in C. jejuni colonization in chickens suggesting that mucosal delivery of live rL. lactis expressing JlpA serves as a promising vaccine platform to induce strong immune-protective responses against C. jejuni in chickens.

Keywords: chickens, lipoprotein adhesion of Campylobacter jejuni, immuno-protection, Lactococcus lactis, mucosal delivery

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4158 Soil and the Gut Microbiome: Supporting the 'Hygiene Hypothesis'

Authors: Chris George, Adam Hamlin, Lily Pereg, Richard Charlesworth, Gal Winter

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Background: According to the ‘hygiene hypothesis’ the current rise in allergies and autoimmune diseases stems mainly from reduced microbial exposure due, amongst other factors, to urbanisation and distance from soil. However, this hypothesis is based on epidemiological and not biological data. Useful insights into the underlying mechanisms of this hypothesis can be gained by studying our interaction with soil. Soil microbiota may be directly ingested or inhaled by humans, enter the body through skin-soil contact or using plants as vectors. This study aims to examine the ability of soil microbiota to colonise the gut, study the interaction of soil microbes with the immune system and their potential protective activity. Method: The nutrition of the rats was supplemented daily with fresh or autoclaved soil for 21 days followed by 14 days of no supplementations. Faecal samples were collected throughout and analysed using 16S sequencing. At the end of the experiment rats were sacrificed and tissues and digesta were collected. Results/Conclusion: Results showed significantly higher richness and diversity following soil supplementation even after recovery. Specific soil microbial groups identified as able to colonise the gut. Of particular interest was the mucosal layer which emerged as a receptive host for soil microorganisms. Histological examination revealed innate and adaptive immune activation. Findings of this study reinforce the ‘hygiene hypothesis’ by demonstrating the ability of soil microbes to colonise the gut and activate the immune system. This paves the way for further studies aimed to examine the interaction of soil microorganisms with the immune system.

Keywords: gut microbiota, hygiene hypothesis, microbiome, soil

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4157 Epigenetic Mechanisms Involved in the Occurrence and Development of Infectious Diseases

Authors: Frank Boris Feutmba Keutchou, Saurelle Fabienne Bieghan Same, Verelle Elsa Fogang Pokam, Charles Ursula Metapi Meikeu, Angel Marilyne Messop Nzomo, Ousman Tamgue

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Infectious diseases are one of the most important causes of morbidity and mortality worldwide. These diseases are caused by micro-pathogenic organisms, such as bacteria, viruses, parasites, and fungi. Heritable changes in gene expression that do not involve changes to the underlying DNA sequence are referred to as epigenetics. Emerging evidence suggests that epigenetic mechanisms are important in the emergence and progression of infectious diseases. Pathogens can manipulate host epigenetic machinery to promote their own replication and evade immune responses. The Human Genome Project has provided new opportunities for developing better tools for the diagnosis and identification of target genes. Several epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNA expression, have been shown to influence infectious disease outcomes. Understanding the epigenetic mechanisms underlying infectious diseases may result in the progression of new therapeutic approaches focusing on host-pathogen interactions. The goal of this study is to show how different infectious agents interact with host cells after infection.

Keywords: epigenetic, infectious disease, micro-pathogenic organism, phenotype

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4156 World War II Vaccination Scheme as a Determinant of Gender-Specific Differences in Anti-Tetanus Antibody Levels in the British Elderly Population

Authors: Myrto Vlazaki

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Tetanus is a non-transmissible, preventable bacterial disease with high mortality. In the U.K., the demographic group systematically accounting for a large proportion of the infections notified to the authorities over the years have been the elderly (> 60 years old). The 2009 seroepidemiological study for tetanus in England reports a gender-age interaction for the +70, with males having significantly higher anti-tetanus antibody levels than females. A systematic review of the literature was carried out to characterise: I. the seroepidemiology of tetanus in economically developed countries with similar immunisation schemes to the U.K., introduced in the 1960’s. II. the factors leading to differential vaccine uptake between males and females in 1910-1945 (corresponding to ages of 60-95 in 2005). III. the immune response elicited by anti-tetanus immunisation in males and females IV. the value of catch-up immunisation in the elderly Similar age- and gender- differences in anti-tetanus antibody levels are noted in other countries. Gender differences in immune responses elicited by vaccination are not consistent with the finding that elder females are less well protected against tetanus compared to their male counterparts. Attention is drawn to the selective anti-tetanus immunisation scheme introduced in the U.K. in 1938, specific to the World War II conscripts. The age-specific immunity gap observed amongst the +70 could be explained as the by-product of that early scheme targetting mostly males. Introducing anti-tetanus vaccination in the +70 in the U.K. could help bridge the immunity gap between males and females and reduce the overall tetanus susceptibility of this age group.

Keywords: elderly, immunisation, gender-specific differences, seroepidemiology, tetanus, World War II

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4155 Mycobacterium tuberculosis and Molecular Epidemiology: An Overview

Authors: Asho Ali

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Tuberculosis is a disease of grave concern which infects one-third of the global population. The high incidence of tuberculosis is further compounded by the increasing emergence of drug resistant strains including multi drug resistant (MDR). Global incidence MDR-TB is ~4%. Molecular epidemiological studies, based on the assumption that patients infected with clustered strains are epidemiologically linked, have helped understand the transmission dynamics of disease. It has also helped to investigate the basis of variation in Mycobacterium tuberculosis (MTB) strains, differences in transmission, and severity of disease or drug resistance mechanisms from across the globe. This has helped in developing strategies for the treatment and prevention of the disease including MDR.

Keywords: Mycobcaterium tuberculosis, molecular epidemiology, drug resistance, disease

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