Search results for: Airway inflammation
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 644

Search results for: Airway inflammation

164 Association of Clostridium difficile Infection and Bone Cancer

Authors: Daniela Prado, Lexi Frankel, Amalia Ardeljan, Lokesh Manjani, Matthew Cardeiro, Omar Rashid

Abstract:

Background: Clostridium difficile (C. diff) is a gram-positive bacterium that is known to cause life-threatening diarrhea and severe inflammation of the colon. It originates as an alteration of the gut microbiome and can be transmitted through spores. Recent studies have shown a high association between the development of C. diff in cancer patients due to extensive hospitalization. However, research is lacking regarding C. diff’s association in the causation or prevention of cancer. The objective of this study was to therefore assess the correlation between Clostridium difficile infection (CDI) and the incidence of bone cancer. Methods: This retrospective analysis used data provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to evaluate the patients infected versus patients not infected with C. diff using ICD-10 and ICD-9 codes. Access to the database was granted by the Holy Cross Health, Fort Lauderdale, for the purpose of academic research. Standard statistical methods were used. Results: Between January 2010 and December 2019, the query was analyzed and resulted in 78863 patients in both the infected and control group, respectively. The two groups were matched by age range and CCI score. The incidence of bone cancer was 659 patients (0.835%) in the C. diff group compared to 1941 patients (2.461%) in the control group. The difference was statistically significant by a P-value < 2.2x10^-16 with an odds ratio (OR)= 0.33 (0.31-0.37) with a 95% confidence interval (CI). Treatment for CDI was analyzed for both C. diff infected and noninfected populations. 91 out of 16,676 (0.55%) patients with a prior C. diff infection and treated with antibiotics were compared to the control group were 275 out of 16,676 (1.65%) patients with no history of CDI and received antibiotic treatment. Results remained statistically significant by P-value <2.2x10-16 with an OR= 0.42 (0.37, 0.48). and a 95% CI. Conclusion: The study shows a statistically significant correlation between C. diff and a reduced incidence of bone cancer. Further evaluation is recommended to assess the potential of C. difficile in reducing bone cancer incidence.

Keywords: bone cancer, colitis, clostridium difficile, microbiome

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163 Clinical Profile, Evaluation, Management and Visual Outcome of Idiopathic Intracranial Hypertension in a Neuro-Ophthalmology Clinic in Jeddah, Saudi Arabia

Authors: Rahaf Mandura

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Background: Idiopathic intracranial hypertension (IIH) is a disorder with elevated intracranial pressure (ICP) more than 250 mm H₂O, without evidence of meningeal inflammation, space-occupying lesion, or venous thrombosis. The aim of this research is to study the clinical profile, evaluation, management, and visual outcome in a hospital-based population of IIH cases in Jeddah. Methodology: This is a retrospective observational study that included the medical records of all patients referred to neuro-ophthalmology service for evaluation of papilledema. The medical records have been reviewed from October 2018 to February 2020 at Jeddah Eye Hospital (JEH), Saudi Arabia. A total of fifty-one patients presented with papilledema in the studied period. Forty-seven patients met our inclusion criteria and were included in the study. Results: Most of the patients were females (43, 91.5%) with a mean age of presentation of 30.83±11.40 years. The most common presenting symptom was headache (40 patients, 85.1%), followed by transient visual obscuration (20 patients, 42.6%), and reduced visual acuity (15 patients, 31.9%). All 47 patients were started on medical treatment with oral acetazolamide with four patients (8.5%) shifted to topiramate because of the lack of response or intolerance to acetazolamide while four patients (8.5%) underwent lumbar-peritoneal shunt because of inadequate control of the disease despite the treatment with medical therapy. For both eyes, the change in visual acuity across all assessment points was statistically significant. Nevertheless, there were no significant changes in the visual field findings among all of the compared assessment points. Conclusion: The present study has shown that IIH-related papilledema is common in young female patients with headaches, transient visual obscurations and reduced visual acuity. Those are the commonest symptoms in our IIH population. Medical treatment of IIH is significantly efficacious and should be considered in order to enhance the prognosis of IIH-related complications. Therefore, the visual status should be frequently monitored for these patients.

Keywords: idiopathic intracranial hypertension, intracranial hypertension, papilledema, headache

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162 Effectiveness of Simulation Resuscitation Training to Improve Self-Efficacy of Physicians and Nurses at Aga Khan University Hospital in Advanced Cardiac Life Support Courses Quasi-Experimental Study Design

Authors: Salima R. Rajwani, Tazeen Ali, Rubina Barolia, Yasmin Parpio, Nasreen Alwani, Salima B. Virani

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Introduction: Nurses and physicians have a critical role in initiating lifesaving interventions during cardiac arrest. It is important that timely delivery of high quality Cardio Pulmonary Resuscitation (CPR) with advanced resuscitation skills and management of cardiac arrhythmias is a key dimension of code during cardiac arrest. It will decrease the chances of patient survival if the healthcare professionals are unable to initiate CPR timely. Moreover, traditional training will not prepare physicians and nurses at a competent level and their knowledge level declines over a period of time. In this regard, simulation training has been proven to be effective in promoting resuscitation skills. Simulation teaching learning strategy improves knowledge level, and skills performance during resuscitation through experiential learning without compromising patient safety in real clinical situations. The purpose of the study is to evaluate the effectiveness of simulation training in Advanced Cardiac Life Support Courses by using the selfefficacy tool. Methods: The study design is a quantitative research design and non-randomized quasi-experimental study design. The study examined the effectiveness of simulation through self-efficacy in two instructional methods; one is Medium Fidelity Simulation (MFS) and second is Traditional Training Method (TTM). The sample size was 220. Data was compiled by using the SPSS tool. The standardized simulation based training increases self-efficacy, knowledge, and skills and improves the management of patients in actual resuscitation. Results: 153 students participated in study; CG: n = 77 and EG: n = 77. The comparison was done between arms in pre and post-test. (F value was 1.69, p value is <0.195 and df was 1). There was no significant difference between arms in the pre and post-test. The interaction between arms was observed and there was no significant difference in interaction between arms in the pre and post-test. (F value was 0.298, p value is <0.586 and df is 1. However, the results showed self-efficacy scores were significantly higher within experimental group in post-test in advanced cardiac life support resuscitation courses as compared to Traditional Training Method (TTM) and had overall (p <0.0001) and F value was 143.316 (mean score was 45.01 and SD was 9.29) verses pre-test result showed (mean score was 31.15 and SD was 12.76) as compared to TTM in post-test (mean score was 29.68 and SD was 14.12) verses pre-test result showed (mean score was 42.33 and SD was 11.39). Conclusion: The standardized simulation-based training was conducted in the safe learning environment in Advanced Cardiac Life Suport Courses and physicians and nurses benefited from self-confidence, early identification of life-threatening scenarios, early initiation of CPR, and provides high-quality CPR, timely administration of medication and defibrillation, appropriate airway management, rhythm analysis and interpretation, and Return of Spontaneous Circulation (ROSC), team dynamics, debriefing, and teaching and learning strategies that will improve the patient survival in actual resuscitation.

Keywords: advanced cardiac life support, cardio pulmonary resuscitation, return of spontaneous circulation, simulation

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161 Comparative Evaluation of Seropositivity and Patterns Distribution Rates of the Anti-Nuclear Antibodies in the Diagnosis of Four Different Autoimmune Collagen Tissue Diseases

Authors: Recep Kesli, Onur Turkyilmaz, Cengiz Demir

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Objective: Autoimmune collagen diseases occur with the immune reactions against the body’s own cell or tissues which cause inflammation and damage the tissues and organs. In this study, it was aimed to compare seropositivity rates and patterns of the anti-nuclear antibodies (ANA) in the diagnosis of four different autoimmune collagen tissue diseases (Rheumatoid Arthritis-RA, Systemic Lupus Erythematous-SLE, Scleroderma-SSc and Sjogren Syndrome-SS) with each other. Methods: One hundred eighty-eight patients applied to different clinics in Afyon Kocatepe University ANS Practice and Research Hospital between 11.07.2014 and 14.07.2015 that thought the different collagen disease such as RA, SLE, SSc and SS have participated in the study retrospectively. All the data obtained from the patients participated in the study were evaluated according to the included criteria. The historical archives belonging to the patients have been screened, assessed in terms of ANA positivity. The obtained data was analysed by using the descriptive statistics; chi-squared, Fischer's exact test. The evaluations were performed by SPSS 20.0 version and p < 0.05 level was considered as significant. Results: Distribution rates of the totally one hundred eighty-eight patients according to the diagnosis were found as follows: 82 (43.6%) were RA, 38 (20.2%) were SLE, 22 (11.7%) were SSc, and 46 (24.5%) were SS. Distribution of ANA positivity rates according to the collagen tissue diseases were found as follows; for RA were 54 (65,9 %), for SLE were 36 (94,7 %), for SSc were 18 (81,8 %), and for SS were 43 (93,5 %). Rheumatoid arthritis should be evaluated and classified as a different class among all the other investigated three autoimmune illnesses. ANA positivity rates were found as differently higher (91.5 %) in the SLE, SSc, and SS, from the RA (65.9 %). Differences at ANA positivity rates for RA and the other three diseases were found as statistically significant (p=0.015). Conclusions: Systemic autoimmune illnesses show broad spectrum. ANA positivity was found as an important predictor marker in the diagnosis of the rheumatologic illnesses. ANA positivity should be evaluated as more valuable and sensitive a predictor diagnostic marker in the laboratory findings of the SLE, SSc, and SS according to RA.

Keywords: antinuclear antibody (ANA), rheumatoid arthritis, scleroderma, Sjogren syndrome, systemic lupus Erythemotosus

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160 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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159 Histological Characteristics of the Organs of Adult Zebrafish as a Biomarker for the Study of New Drugs with Effect on the Snake Venom of Bothrops alternatus

Authors: Jose Carlos Tavares Carvalho, Hady Keita, Giovanna Rocha Santana, Igor Victor Ferreira Dos Santos, Jesus Rafael Rodriguez Amado, Ariadna Lafourcade Prada, Adriana Maciel Ferreira, Helison Oliveira

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Summary: As animal model, zebrafish can be a good opportunity to establish a profile of tissue alteration caused by Bothrops alternatus venom and to screen new anti-venom drugs. Objective: To establish tissue biomarkers from zebrafish injected by snake venom and elucidate the use of glucocorticoids in ophidic accidents. Materials and Methods: The Danio rerio fish were randomly divided into four groups: control group, venom group, Dexamethasone1h before venom injected group and Dexamethasone 1 h after venom injected group. The concentration of Bothrops alternatus venom was 0.13 mg/ml and the fish received 20µl/Fish. The Body weight measurement and histological characteristics of gills, kidneys, liver, and intestine were determinate. Results: Physical analysis shows necrosis accompanied by inflammation in animals receiving the Bothrops alternatus venom. Significant difference was observed in the variation of weight between the control group, and the groups received the venom (t student test, p < 0.05). The average histological alterations index of gill, liver, kidney or intestine was statistically higher in animals received the venom (t Student test, p < 0.05). The alterations were lower in the groups that received Dexamethasone 1h before and after venom injected compared to the group that received only the venom. Dexamethasone 1h before venom injected group had minor histopathological alterations. Conclusion: The organs of zebrafish may be a tissue biomarker of alterations from Bothrops alternatus venom and dexamethasone reduced the damage caused by this venom in the organs studied, which may suggest the use of zebrafish as animal model for research related to screening new drug against snake venom.

Keywords: zebrafish, snake venom, biomarker, drugs

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158 Autophagy Acceleration and Self-Healing by the Revolution against Frequent Eating, High Glycemic and Unabsorbable Substances as One Meal a Day Plan

Authors: Reihane Mehrparvar

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Human age could exceed further by altering gene expression through food intaking, although as a consequence of recent century eating patterns, human life-span getting shorter by emerging irregulating in autophagy mechanism, insulin, leptin, gut microbiota which are important etiological factors of type-2 diabetes, obesity, infertility, cancer, metabolic and autoimmune diseases. However, restricted calorie intake and vigorous exercise might be beneficial for losing weight and metabolic regulation in a short period but could not be implementable in the long term as a way of life. Therefore, the lack of a dietary program that is compatible with the genes of the body is essential. Sweet and high-glycemic-index (HGI) foods were associated with type-2 diabetes and cancer morbidity. The neuropsychological perspective characterizes the inclination of sweet and HGI-food consumption as addictive behavior; hence this process engages preference of gut microbiota, neural node, and dopaminergic functions. Moreover, meal composition is not the only factor that affects body hemostasis. In this narrative review, it is believed to attempt to investigate how the body responded to different food intakes and represent an accurate model based on current evidence. Eating frequently and ingesting unassimilable protein and carbohydrates may not be compatible with human genes and could cause impairments in the self-renovation mechanism. This trajectory indicates our body is more adapted to starvation and eating animal meat and marrow. Here has been recommended a model that takes into account three important factors: frequent eating, meal composition, and circadian rhythm, which may offer a promising intervention for obesity, inflammation, cardiovascular, autoimmune disorder, type-2 diabetes, insulin resistance, infertility, and cancer through intensifying autophagy-mechanism and eliminate medical costs.

Keywords: metabolic disease, anti-aging, type-2 diabetes, autophagy

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157 Murine Pulmonary Responses after Sub-Chronic Exposure to Environmental Ultrafine Particles

Authors: Yara Saleh, Sebastien Antherieu, Romain Dusautoir, Jules Sotty, Laurent Alleman, Ludivine Canivet, Esperanza Perdrix, Pierre Dubot, Anne Platel, Fabrice Nesslany, Guillaume Garcon, Jean-Marc Lo-Guidice

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Air pollution is one of the leading causes of premature death worldwide. Among air pollutants, particulate matter (PM) is a major health risk factor, through the induction of cardiopulmonary diseases and lung cancers. They are composed of coarse, fine and ultrafine particles (PM10, PM2.5, and PM0.1 respectively). Ultrafine particles are emerging unregulated pollutants that might have greater toxicity than larger particles, since they are more abundant and consequently have higher surface area per unit of mass. Our project aims to develop a relevant in vivo model of sub-chronic exposure to atmospheric particles in order to elucidate the specific respiratory impact of ultrafine particles compared to fine particulate matter. Quasi-ultrafine (PM0.18) and fine (PM2.5) particles have been collected in the urban industrial zone of Dunkirk in north France during a 7-month campaign, and submitted to physico-chemical characterization. BALB/c mice were then exposed intranasally to 10µg of PM0.18 or PM2.5 3 times a week. After 1 or 3-month exposure, broncho alveolar lavages (BAL) were performed and lung tissues were harvested for histological and transcriptomic analyses. The physico-chemical study of the collected particles shows that there is no major difference in elemental and surface chemical composition between PM0.18 and PM2.5. Furthermore, the results of the cytological analyses carried out show that both types of particulate fractions can be internalized in lung cells. However, the cell count in BAL and preliminary transcriptomic data suggest that PM0.18 could be more reactive and induce a stronger lung inflammation in exposed mice than PM2.5. Complementary studies are in progress to confirm these first data and to identify the metabolic pathways more specifically associated with the toxicity of ultrafine particles.

Keywords: environmental pollution, lung affect, mice, ultrafine particles

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156 CICAP: Promising Wound Healing Gel from Bee Products and Medicinal Plants

Authors: Laïd Boukraâ

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Complementary and Alternative Medicine is an inclusive term that describes treatments, therapies, and modalities that are not accepted as components of mainstream education or practice, but that are performed on patients by some practitioners. While these treatments and therapies often form part of post-graduate education, study and writing, they are generally viewed as alternatives or complementary to more universally accepted treatments. Ancient civilizations used bee products and medicinal plants, but modern civilization and ‘education’ have seriously lessened our natural instinctive ability and capability. Despite the fact that the modern Western establishment appears to like to relegate apitherapy and aromatherapy to the status of 'folklore' or 'old wives' tales', they contain a vast spread of pharmacologically-active ingredients and each one has its own unique combination and properties. They are classified in modern herbal medicine according to their spheres of action. Bee products and medicinal plants are well-known natural product for their healing properties and their increasing popularity recently as they are widely used in wound healing. Honey not only has antibacterial properties which can help as an antibacterial agent but also has chemical properties which may further help in the wound healing process. A formulation with honey as its main component was produced into a honey gel. This new formulation has enhanced texture and is more user friendly for usage as well. This new formulation would be better than other formulas as it is hundred percent consisting of natural products and has been made into a better formulation. In vitro assay, animal model study and clinical trials have shown the effectiveness of LEADERMAX for the treatment of diabetic foot, burns, leg ulcer and bed sores. This one hundred percent natural product could be the best alternative to conventional products for wound and burn management. The advantages of the formulation are: 100% natural, affordable, easy to use, strong power of absorption, dry surface on the wound making a film, will not stick to the wound bed; helps relieve wound pain, inflammation, edema and bruising while improving comfort.

Keywords: bed sore bee products, burns, diabetic foot, medicinal plants, leg ulcer, wounds

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155 Increased Expression Levels of Soluble Epoxide Hydrolase in Obese and Its Modulation by Physical Exercise

Authors: Abdelkrim Khadir, Sina Kavalakatt, Preethi Cherian, Ali Tiss

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Soluble epoxide hydrolase (sEH) is an emerging therapeutic target in several chronic states that have inflammation as a common underlying cause such as immunometabolic diseases. Indeed, sEH is known to play a pro-inflammatory role by metabolizing anti-inflammatory, epoxyeicosatrienoic acids (EETs) to pro-inflammatory diols. Recently, it was shown sEH to be linked to diet and microbiota interaction in rat models of obesity. Nevertheless, the functional contribution of sEH and its anti-inflammatory substrates EETs in obesity remain poorly understood. In the current study, we compared the expression pattern of sEH between lean and obese nondiabetic human subjects using subcutaneous adipose tissue (SAT) and peripheral blood mononuclear cells (PBMCs). Using RT-PCR, western blot and immunofluorescence confocal microscopy, we show here that the level of sEH mRNA and protein to be significantly increased in obese subjects with concomitant increase in endoplasmic reticulum (ER) stress components (GRP78 and ATF6α) and inflammatory markers (TNF-α, IL-6) when compared to lean controls. The observation that sEH was overexpressed in obese subjects’ prompt us to investigate whether physical exercise could reduce its expression. In this study, we report here 3-months supervised physical exercise significantly attenuated the expression of sEH in both the SAT and PBMCs, with a parallel decrease in the expression of ER stress markers along with attenuated inflammatory response. On the other hand, homocysteine, a sulfur containing amino acid deriving from the essential amino acid methionine was shown to be directly associated with insulin resistance. When 3T3-L1 preadipocytes cells were treated with homocysteine our results show increased sEH levels along with ER stress markers. Collectively, our data suggest that sEH upregulation is strongly linked to ER stress in adiposity and that physical exercise modulates its expression. This gives further evidence that exercise might be useful as a strategy for managing obesity and preventing its associated complications.

Keywords: obesity, adipose tissue, epoxide hydrolase, ER stress

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154 Protective Effect of Probiotic Lactic Acid Bacteria on Thioacetamide-Induced Liver Fibrosis in Rats: Histomorphological Study

Authors: Chittapon Jantararussamee, Malai Taweechotipatr, Udomsri Showpittapornchai, Wisuit Pradidarcheep

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Hepatic fibrosis is characterized by collagen accumulation in hepatic lobules following wound healing process. If lefts untreated, it could progress into hepatic cirrhosis, portal hypertension, and liver failure. Probiotics comprise of lactic acid bacteria which are crucial components of the intestinal microflora and possess many beneficial properties. The objective of this study is to investigate the hepatoprotective effects of probiotic lactic acid bacteria (mixture of Lactobacillus paracasei, Lactobacillus casei, and Lactobacillus confusus at a ratio of 1: 1: 1) on thioacetamide-induced liver fibrotic rats in term of histomorphology study. Twenty-four male Wistar rats were randomly divided into four groups with 6 rats each: (A) control, (B) fibrotic, (C) fibrotic+probiotic, and (D) probiotic. Group (A) received daily oral administration of distilled water. Group (B and C) were induced by intraperitoneal injection of thioacetamide (TAA) (200 mg/kg BW) 3 times per week for consecutive 8 weeks. In probiotic-treated group (C and D), the number of a mixture of the viable microbial cells at 10⁹ CFU/ml was administered orally daily. After sacrifice, liver tissues were collected and processed for routine histological technique and stained with Sirius red. It was found that the fibrotic rats showed hepatic injury marked by area of inflammation, hydropic degeneration of hepatocytes, and accumulation of myofibroblast-like cells. The collagen fibers were substantially accumulated in the hepatic lobules. Moreover, probiotic-treated group significantly reduced the accumulation of collagen in rats treated by TAA. The liver damage was found to be lesser in the probiotic-treated group. It was noted that the liver tissues of control and probiotics groups were shown to be normal. Administration with probiotic lactic acid bacteria could improve the histomorphology in fibrotic liver and be useful for prevention of hepatic disorders.

Keywords: liver fibrosis, probiotics, lactic acid bacteria, thioacetamide

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153 Nano-Plasmonic Diagnostic Sensor Using Ultraflat Single-Crystalline Au Nanoplate and Cysteine-Tagged Protein G

Authors: Hwang Ahreum, Kang Taejoon, Kim Bongsoo

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Nanosensors for high sensitive detection of diseases have been widely studied to improve the quality of life. Here, we suggest robust nano-plasmonic diagnostic sensor using cysteine tagged protein G (Cys3-protein G) and ultraflat, ultraclean and single-crystalline Au nanoplates. Protein G formed on an ultraflat Au surface provides ideal background for dense and uniform immobilization of antibodies. The Au is highly stable in diverse biochemical environment and can immobilize antibodies easily through Au-S bonding, having been widely used for various biosensing applications. Especially, atomically smooth single-crystalline Au nanomaterials synthesized using chemical vapor transport (CVT) method are very suitable to fabricate reproducible sensitive sensors. As the C-reactive protein (CRP) is a nonspecific biomarker of inflammation and infection, it can be used as a predictive or prognostic marker for various cardiovascular diseases. Cys3-protein G immobilized uniformly on the Au nanoplate enable CRP antibody (anti-CRP) to be ordered in a correct orientation, making their binding capacity be maximized for CRP detection. Immobilization condition for the Cys3-protein G and anti-CRP on the Au nanoplate is optimized visually by AFM analysis. Au nanoparticle - Au nanoplate (NPs-on-Au nanoplate) assembly fabricated from sandwich immunoassay for CRP can reduce zero-signal extremely caused by nonspecific bindings, providing a distinct surface-enhanced Raman scattering (SERS) enhancement still in 10-18 M of CRP concentration. Moreover, the NP-on-Au nanoplate sensor shows an excellent selectivity against non-target proteins with high concentration. In addition, comparing with control experiments employing a Au film fabricated by e-beam assisted deposition and linker molecule, we validate clearly contribution of the Au nanoplate for the attomolar sensitive detection of CRP. We expect that the devised platform employing the complex of single-crystalline Au nanoplates and Cys3-protein G can be applied for detection of many other cancer biomarkers.

Keywords: Au nanoplate, biomarker, diagnostic sensor, protein G, SERS

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152 The Comparison of the Effects of Adipose-Derived Mesenchymal Stem Cells Delivery by Systemic and Intra-Tracheal Injection on Elastase-Induced Emphysema Model

Authors: Maryam Radan, Fereshteh Nejad Dehbashi, Vahid Bayati, Mahin Dianat, Seyyed Ali Mard, Zahra Mansouri

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Pulmonary emphysema is a pathological respiratory condition identified by alveolar destruction which leads to limitation of airflow and diminished lung function. A substantial body of evidence suggests that mesenchymal stem cells (MSCs) have the ability to induce tissue repair primarily through a paracrine effect. In this study, we aimed to determine the efficacy of Intratracheal adipose-derived mesenchymal stem cells (ADSCs) therapy in comparison to this approach with that of Intravenous (Systemic) therapy. Fifty adult male Sprague–Dawley rats weighing between 180 and 200 g were used in this experiment. The animals were randomized to Control groups (Intratracheal or Intravenous vehicle), Elastase group (intratracheal administration of porcine pancreatic elastase; 25 U/kg on day 0 and day 10th), Elastase+Intratracheal ADSCs therapy (1x107 Cells, on day 28) and Elastase+Systemic ADSCs therapy (1x107 Cells, on day 28). The rats which not subjected to any treatment, considered as the control. All rats were sacrificed 3 weeks later. Morphometric findings in lung tissues (Mean linear intercept) confirmed the establishment of the emphysema model via alveolar disruption. Contrarily, ADSCs administration partially restored alveolar architecture. These results were associated with improving arterial oxygenation, reducing lung edema, and decreasing lung inflammation with higher significant effects in the Intratracheal therapy route. These results documented that the efficacy of intratracheal ADSCs was comparable with intravenous ADSCs therapy. Accordingly, the obtained data suggested that intratracheal delivery of ADSCs would enhance lung repair in pulmonary emphysema. Moreover, this method provides benefits over a systemic administration, such as the reduction of cell number and the low risk to engraft other organs.

Keywords: mesenchymal stem cell, emphysema, Intratracheal, systemic

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151 Assessment of Platelet and Lymphocyte Interaction in Autoimmune Hyperthyroidism

Authors: Małgorzata Tomczyńska, Joanna Saluk-Bijak

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Background: Graves’ disease is a frequent organ-specific autoimmune thyroid disease, which characterized by the presence of different kind autoantibodies, that, in most cases, act as agonists of the thyrotropin receptor, leading to hyperthyroidism. Role of platelets and lymphocytes can be modulated in the pathophysiology of thyroid autoimmune diseases. Interference in the physiology of platelets can lead to enhanced activity of these cells. Activated platelets can bind to circulating lymphocytes and to affect lymphocyte adhesion. Platelets and lymphocytes can regulate mutual functions. Therefore, the activation of T lymphocytes, as well as blood platelets, is associated with the development of inflammation and oxidative stress within the target tissue. The present study was performed to investigate a platelet-lymphocyte relation by assessing the degree of their mutual aggregation in whole blood of patients with Graves’ disease. Also, the purpose of this study was to examine the impact of platelet interaction on lymphocyte migration capacity. Methods: 30 patients with Graves’ disease were recruited in the study. The matched 30 healthy subjects were served as the control group. Immunophenotyping of lymphocytes was carried out by flow cytometry method. A CytoSelect™ Cell Migration Assay Kit was used to evaluate lymphocyte migration and adhesion to blood platelets. Visual assessment of lymphocyte-platelet aggregate morphology was done using confocal microscope after magnetic cell isolation by Miltenyi Biotec. Results: The migration and functional responses of lymphocytes to blood platelets were greater in the group of Graves’ disease patients compared with healthy controls. The group of Graves’ disease patients exhibited a reduced T lymphocyte and a higher B cell count compared with controls. Based on microscopic analysis, more platelet-lymphocyte aggregates were found in patients than in control. Conclusions: Studies have shown that in Graves' disease, lymphocytes show increased platelet affinity, more strongly migrating toward them, and forming mutual cellular conglomerates. This may be due to the increased activation of blood platelets in this disease.

Keywords: blood platelets, cell migration, Graves’ disease, lymphocytes, lymphocyte-platelet aggregates

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150 Efficacy and Mechanisms of Acupuncture for Depression: A Meta-Analysis of Clinical and Preclinical Evidence

Authors: Yimeng Zhang

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Major depressive disorder (MDD) is a prevalent mental health condition with a substantial economic impact and limited treatment options. Acupuncture has gained attention as a promising non-pharmacological intervention for alleviating depressive symptoms. However, its mechanisms and clinical effectiveness remain incompletely understood. This meta-analysis aims to (1) synthesize existing evidence on the mechanisms and clinical effectiveness of acupuncture for depression and (2) compare these findings with pharmacological interventions, providing insights for future research. Evidence from animal models and clinical studies indicates that acupuncture may enhance hippocampal and network neuroplasticity and reduce brain inflammation, potentially alleviating depressive disorders. Clinical studies suggest that acupuncture can effectively relieve primary depression, particularly in milder cases, and is beneficial in managing post-stroke depression, pain-related depression, and postpartum depression, both as a standalone and adjunctive treatment. Notably, combining acupuncture with antidepressant pharmacotherapy appears to enhance treatment outcomes and reduce medication side effects, addressing a critical issue in conventional drug therapy's high dropout rates. This meta-analysis, encompassing 12 studies and 710 participants, draws data from eight digital databases (PubMed, EMBASE, Web of Science, EBSCOhost, CNKI, CBM, Wangfang, and CQVIP) covering the period from 2012 to 2022. Utilizing Stata software 15.0, the meta-analysis employed random-effects and fixed-effects models to assess the distribution of depression in Traditional Chinese Medicine (TCM). The results underscore the substantial evidence supporting acupuncture's beneficial effects on depression. However, the small sample sizes of many clinical trials raise concerns about the generalizability of the findings, indicating a need for further research to validate these outcomes and optimize acupuncture's role in treating depression.

Keywords: Chinese medicine, acupuncture, depression, meta-analysis

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149 Development of an Experimental Model of Diabetes Co-Existing with Metabolic Syndrome in Rats

Authors: Rajesh Kumar Suman, Ipseeta Ray Mohanty, Manjusha K. Borde, Ujjawala maheswari, Y. A. Deshmukh

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Background: Metabolic syndrome encompasses cluster of risk factors for cardiovascular disease which includes abdominal obesity, dyslipidemia, hypertension, and hyperglycemia. The incidence of metabolic syndrome is on the rise globally. Objective: The present study was designed to develop a unique animal model that will mimic the pathological features seen in a large pool of individuals with diabetes and metabolic syndrome; suitable for pharmacological screening of drugs beneficial in this condition. Material and Methods: A combination of high fat diet (HFD) and low dose of streptozotocin (STZ) at 30, 35 and 40 mg/kg was used to induce metabolic syndrome co-existing with diabetes mellitus in Wistar rats. Results: The 40 mg/kg STZ produced sustained hyperglycemia and the dose was thus selected for our study to induce diabetes mellitus. Rat fed HFD (HF-DC) group showed significant (p < 0.001) increase in body weight on 4th and 7th week as compared with NC (Normal Control) group rats. However, the increase in body weight of HF-DC group rats was not sustained at the end of 10th weeks. Various components of metabolic syndrome such as dyslipidemia {(Increased Triglyceride, total Cholesterol, LDL Cholesterol and decreased HDL Cholesterol)}, diabetes mellitus (Blood Glucose, HbA1c, Serum Insulin, C-peptide), hypertension {Systolic Blood pressure (p < 0.001)} were mimicked in the developed model of metabolic syndrome co existing with diabetes mellitus. In addition significant cardiac injury as indicated by CPK-MB levels, artherogenic index, hs-CRP. The decline in hepatic function {(p < 0.01) increase in the level of SGPT (U/L)} and renal function {(increase in creatinine levels (p < 0.01)} when compared to NC group rats. The histopathological assessment confirmed presence of edema, necrosis and inflammation in Heart, Pancreas, Liver and Kidney of HFD-DC group as compared to NC. Conclusion: The present study has developed a unique rodent model of metabolic syndrome; with diabetes as an essential component.

Keywords: diabetes, metabolic syndrome, high fat diet, streptozotocin, rats

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148 Montelukast Doesn’t Decrease the Risk of Cardiovascular Disease in Asthma Patients in Taiwan

Authors: Sheng Yu Chen, Shi-Heng Wang

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Aim: Based on human, animal experiments, and genetic studies, cysteinyl leukotrienes, LTC4, LTD4, and LTE4, are inflammatory substances that are metabolized by 5-lipooxygenase from arachidonic acid, and these substances trigger asthma. In addition, the synthetic pathway of cysteinyl leukotriene is relevant to the increase in cardiovascular diseases such as myocardial ischemia and stroke. Given the situation, we aim to investigate whether cysteinyl leukotrienes receptor antagonist (LTRA), montelukast which cures those who have asthma has potential protective effects on cardiovascular diseases. Method: We conducted a cohort study, and enrolled participants which are newly diagnosed with asthma (ICD-9 CM code 493. X) between 2002 to 2011. The data source is from Taiwan National Health Insurance Research Database Patients with a previous history of myocardial infarction or ischemic stroke were excluded. Among the remaining participants, every montelukast user was matched with two randomly non-users by sex, and age. The incident cardiovascular diseases, including myocardial infarction and ischemic stroke, were regarded as outcomes. We followed the participants until outcomes come first or the end of the following period. To explore the protective effect of montelukast on the risk of cardiovascular disease, we use multivariable Cox regression to estimate the hazard ratio with adjustment for potential confounding factors. Result: There are 55876 newly diagnosed asthma patients who had at least one claim of inpatient admission or at least three claims of outpatient records. We enrolled 5350 montelukast users and 10700 non-users in this cohort study. The following mean (±SD) time of the Montelukast group is 5 (±2.19 )years, and the non-users group is 6.2 5.47 (± 2.641) years. By using multivariable Cox regression, our analysis indicated that the risk of incident cardiovascular diseases between montelukast users (n=43, 0.8%) and non-users (n=111, 1.04%) is approximately equal. [adjusted hazard ratio 0.992; P-value:0.9643] Conclusion: In this population-based study, we found that the use of montelukast is not associated with a decrease in incident MI or IS.

Keywords: asthma, inflammation, montelukast, insurance research database, cardiovascular diseases

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147 Electrochemical Bioassay for Haptoglobin Quantification: Application in Bovine Mastitis Diagnosis

Authors: Soledad Carinelli, Iñigo Fernández, José Luis González-Mora, Pedro A. Salazar-Carballo

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Mastitis is the most relevant inflammatory disease in cattle, affecting the animal health and causing important economic losses on dairy farms. This disease takes place in the mammary gland or udder when some opportunistic microorganisms, such as Staphylococcus aureus, Streptococcus agalactiae, Corynebacterium bovis, etc., invade the teat canal. According to the severity of the inflammation, mastitis can be classified as sub-clinical, clinical and chronic. Standard methods for mastitis detection include counts of somatic cells, cell culture, electrical conductivity of the milk, and California test (evaluation of “gel-like” matrix consistency after cell lysed with detergents). However, these assays present some limitations for accurate detection of subclinical mastitis. Currently, haptoglobin, an acute phase protein, has been proposed as novel and effective biomarker for mastitis detection. In this work, an electrochemical biosensor based on polydopamine-modified magnetic nanoparticles (MNPs@pDA) for haptoglobin detection is reported. Thus, MNPs@pDA has been synthesized by our group and functionalized with hemoglobin due to its high affinity to haptoglobin protein. The protein was labeled with specific antibodies modified with alkaline phosphatase enzyme for its electrochemical detection using an electroactive substrate (1-naphthyl phosphate) by differential pulse voltammetry. After the optimization of assay parameters, the haptoglobin determination was evaluated in milk. The strategy presented in this work shows a wide range of detection, achieving a limit of detection of 43 ng/mL. The accuracy of the strategy was determined by recovery assays, being of 84 and 94.5% for two Hp levels around the cut off value. Milk real samples were tested and the prediction capacity of the electrochemical biosensor was compared with a Haptoglobin commercial ELISA kit. The performance of the assay has demonstrated this strategy is an excellent and real alternative as screen method for sub-clinical bovine mastitis detection.

Keywords: bovine mastitis, haptoglobin, electrochemistry, magnetic nanoparticles, polydopamine

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146 Development of Ketorolac Tromethamine Encapsulated Stealth Liposomes: Pharmacokinetics and Bio Distribution

Authors: Yasmin Begum Mohammed

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Ketorolac tromethamine (KTM) is a non-steroidal anti-inflammatory drug with a potent analgesic and anti-inflammatory activity due to prostaglandin related inhibitory effect of drug. It is a non-selective cyclo-oxygenase inhibitor. The drug is currently used orally and intramuscularly in multiple divided doses, clinically for the management arthritis, cancer pain, post-surgical pain, and in the treatment of migraine pain. KTM has short biological half-life of 4 to 6 hours, which necessitates frequent dosing to retain the action. The frequent occurrence of gastrointestinal bleeding, perforation, peptic ulceration, and renal failure lead to the development of other drug delivery strategies for the appropriate delivery of KTM. The ideal solution would be to target the drug only to the cells or tissues affected by the disease. Drug targeting could be achieved effectively by liposomes that are biocompatible and biodegradable. The aim of the study was to develop a parenteral liposome formulation of KTM with improved efficacy while reducing side effects by targeting the inflammation due to arthritis. PEG-anchored (stealth) and non-PEG-anchored liposomes were prepared by thin film hydration technique followed by extrusion cycle and characterized for in vitro and in vivo. Stealth liposomes (SLs) exhibited increase in percent encapsulation efficiency (94%) and 52% percent of drug retention during release studies in 24 h with good stability for a period of 1 month at -20°C and 4°C. SLs showed about maximum 55% of edema inhibition with significant analgesic effect. SLs produced marked differences over those of non-SL formulations with an increase in area under plasma concentration time curve, t₁/₂, mean residence time, and reduced clearance. 0.3% of the drug was detected in arthritic induced paw with significantly reduced drug localization in liver, spleen, and kidney for SLs when compared to other conventional liposomes. Thus SLs help to increase the therapeutic efficacy of KTM by increasing the targeting potential at the inflammatory region.

Keywords: biodistribution, ketorolac tromethamine, stealth liposomes, thin film hydration technique

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145 Healthy Beverages Made from Grape Juice: Antioxidant, Energetic, and Isotonic Components

Authors: Yasmina Bendaali, Cristian Vaquero, Carlos Escott, Carmen González, Antonio Morata

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Consumer tendencies to healthy eating habits and request for organic beverages led to the production of new drinks from fruit juices as a source of nutrients and bioactive compounds. Grape juice is a rich source of sugars, organic acids, and phenolic compounds, which define its beneficial effect on health and the attractive sensory profile for consumers' choices (color, taste, flavor). Thus, grape juice was used as a source of sugars, avoiding the addition of sweeteners by diluting it with mineral water to obtain the sugar concentration recommended for isotonic drinks (6% to 8%) to provide energy during physical activities. In addition, phenolic compounds of grape juice are associated with many human health benefits, mainly antioxidant activity, which helps to prevent different diseases associated with oxidative stress, including cancers and cardiovascular and neurodegenerative diseases. Furthermore, physical exercise has been shown to increase the production of free radicals and other reactive oxygen species. Thus, athletes need to improve their antioxidant defense systems to prevent oxidative damage. Different studies have demonstrated the positive effect of grape juice consumption during physical activities, which improves antioxidant activity and performance, protects against oxidative damage, and reduces inflammation. Thus, the use of grape juice to develop isotonic drinks can provide isotonic drinks with antioxidant and biological activities in addition to their principal role of rehydration and replacement of minerals and carbohydrates during physical exercises. Moreover, attractive sensory characteristics, mainly color, which is provided by anthocyanin content, have a great contribution to making the drinks more natural and help to dispense the use of synthetic dyes in addition to the health benefits which will be a novel product in the field of healthy beverages responding on the demand of consumers for new, innovative, and healthy products.

Keywords: grape juice, isotonic, antioxidants, anthocyanins, natural, sport

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144 Air Pollutants Exposure and Blood High Sensitivity C-Reactive Protein Concentrations in Healthy Pregnant Women

Authors: Gwo-Hwa Wan, Tai-Ho Hung, Fen-Fang Chung, Wan-Ying Lee, Hui-Ching Yang

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Air pollutant exposure results in elevated concentrations of oxidative stress and inflammatory biomarkers in general populations. Increased concentrations of inflammatory biomarkers in pregnant women would be associated with preterm labor and low birth weight. To our best knowledge, the associations between air pollutants exposure and inflammation in pregnant women and fetuses are unknown, as well as their effects on fetal growth. This study aimed to evaluate the influences of outdoor air pollutants in northern Taiwan areas on the inflammatory biomarker (high sensitivity C-reactive protein, hs-CRP) concentration in the blood of healthy pregnant women and how the biomarker impacts fetal growth. In this study, 38 healthy pregnant women who are in their first trimester and live in northern Taiwan area were recruited from the Taipei Chang Gung Memorial Hospital. Personal characteristics and prenatal examination data (e.g., blood pressure) were obtained from recruited subjects. The concentrations of inflammatory mediators, hs-CRP, in the blood of healthy pregnant women were analyzed. Additionally, hourly data of air pollutants (PM10, SO2, NO2, O3, CO) concentrations were obtained from air quality monitoring stations in Taipei area, established by the Taiwan Environmental Protection Administration. The definition of lag 0 and lag 01 are the exposure to air pollutants on the day of blood withdrawal, and the average exposure to air pollutants one day before and on the day of blood withdrawal, respectively. The statistical analyses were conducted using SPSS software version 22.0 (SPSS, Inc., Chicago, IL, USA). This analytical result indicates that the healthy pregnant women aged between 28 and 42 years old. The body mass index before pregnancy averaged 21.51 (sd = 2.51) kg/m2. Around 90% of the pregnant women had never smoking habit, and 28.95% of them had allergic diseases. Approximately around 84% and 5.26% of the pregnant women worked at indoor and outdoor environments, respectively. The mean hematocrit level of the pregnant women was 37.10%, and the hemoglobin levels were ranged between 10.1 and 14.7 g/dL with 12.47 g/dL of mean value. The blood hs-CRP concentrations of healthy pregnant women in the first trimester ranged between 0.32 and 32.5 mg/L with 2.83 (sd = 5.69) mg/L of mean value. The blood hs-CRP concentrations were positively associated with ozone concentrations at lag 0-14 (r = 0.481, p = 0.017) in healthy pregnant women. Significant lag effects were identified in ozone at lag 0-14 with a positive excess concentration of blood hs-CRP.

Keywords: air pollutant, hs-CRP, pregnant woman, ozone, first trimester

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143 Effect of Psychological Stress to the Mucosal IL-6 and Helicobacter pylori Activity in Functional Dyspepsia and Myocytes

Authors: Eryati Darwin, Arina Widya Murni, Adnil Edwin Nurdin

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Background: Functional dyspepsia (FD) is a highly prevalent and heterogeneous disorder. Most patients with FD complain of symptoms related to the intake of meals. Psychological stress may promote peptic ulcer and had an effect on ulcers associated Hp, and may also trigger worsen symptoms in inflammatory disorders of the gastrointestinal. Cells in mucosal gastric stimulate the production of several cytokines, which might associated with Helicobacter pylori infection. The cascade of biological events leading to stress-induced FD remains poorly understood. Aim of Study: To determine the prion-flammatory cytokine IL-6, and Helicobacter pylori activity on mucosal gastric of FD and their association with psychological stress. Methods: The subjects of this study were dyspeptic patients who visited M. Djamil General Hospital and in two Community Health Centers in Padang. On the basis of the stress index scale to identify psychological stress by using Depression Anxiety and Stress Scale (DASS 42), subjects were divided into two groups of 20 each, stress groups and non-stress groups. All diagnoses were confirmed by review of cortisol and esophagogastroduodenoscopy reports. Gastric biopsy samples and peripheral blood were taken during diagnostic procedures. Immunohistochemistry methods were used to determine the expression of IL-6 and Hp in gastric mucosal. The data were statistically analyzed by univariate and bivariate analysis. All procedures of this study were approved by Research Ethics Committee of Medical Faculty Andalas University. Results: In this study, we enrolled 40 FD patients (26 woman and 14 men) in range between 35-56 years old. Cortisol level of blood FD patients as parameter of stress hormone which taken in the morning was significantly higher in stress group than non-stress group. The expression of IL-6 in gastric mucosa was significantly higher in stress group in compared to non-stress group (p<0,05). Helicobacter pylori activity in gastric mucosal in stress group were significantly higher than non-stress group. Conclusion: The present study showed that psychological stress can induce gastric mucosal inflammation and increase of Helicobacter pylori activity.

Keywords: functional dyspepsia, Helicobacter pylori, interleukin-6, psychological stress

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142 The Correlation between Clostridium Difficile Infection and Bronchial Lung Cancer Occurrence

Authors: Molnar Catalina, Lexi Frankel, Amalia Ardeljan, Enoch Kim, Marissa Dallara, Omar Rashid

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Introduction: Clostridium difficile (C. diff) is a toxin-producing bacteria that can cause diarrhea and colitis. U.S. Center for Disease Control and Prevention revealed that C. difficile infection (CDI) has increased from 31 cases per 100,000 persons per year in 1996 to 61 per 100,000 in 2003. Approximately 500,000 cases per year occur in the United States. After exposure, the bacteria colonize the colon, where it adheres to the intestinal epithelium where it produces two toxins: TcdA and TcdB. TcdA affects the intestinal epithelium, causing fluid secretion, inflammation, and tissue necrosis, while TcdB acts as a cytotoxin purpose of this study was to evaluate the association between C diff infection and bronchial lung cancer development. Methods: Using ICD- 9 and ICD-10 codes, the data was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to assess the patients infected with C diff as opposed to the non-infected patients. The Holy Cross Health, Fort Lauderdale, granted access to the database for the purpose of academic research. Patients were matched for age and Charlson Comorbidity Index (CCI). Standard statistical methods were used. Results: Bronchial lung cancer occurrence in the population not infected with C diff infection was 4741, as opposed to the population infected with C. diff, where 2039 cases of lung cancer were observed. The difference was statistically significant (p-value < 2.2x10^e-16), which reveals that C diff might be protective against bronchial lung cancer. The data was then matched by treatment to create to minimize the effect of treatment bias. Bronchial cancer incidence was 422 and 861 in infected vs. non-infected (p-value of < 2.2x10^e-16), which once more indicates that C diff infection could be beneficial in diminishing bronchial cancer development. Conclusion: This retrospective study conveys a statistical correlation between C diff infection and decreased incidence of lung bronchial cancer. Further studies are needed to comprehend the protective mechanisms of C. Diff infection on lung cancer.

Keywords: C. diff, lung cancer, protective, microbiology

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141 Beneficial Effects of Curcumin against Stress Oxidative and Mitochondrial Dysfunction Induced by Trinitrobenzene Sulphonic Acid in Colon

Authors: Souad Mouzaoui, Bahia Djerdjouri

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Oxidative stress is one of the main factors involved in the onset and chronicity of inflammatory bowel disease (IBD). In this study, we investigated the beneficial effects of a potent natural antioxidant, curcumin (Cur) on colitis and mitochondrial dysfunction in trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Rectal instillation of the chemical irritant TNBS (30 mg kg-1) induced the disruption of distal colonic architecture and a massive inflammatory cells influx to the mucosa and submucosa layers. Under these conditions, daily administration of Cur (25 mg kg-1) efficiently decreased colitis scores in the inflamed distal colon by reducing leukocyte infiltrate as attested by reduced myeloperoxidase (MPO) activity. Moreover, the levels of nitrite, an end product of inducible NO synthase activity (iNOS) and malonyl dialdehyde (MDA), a marker of lipid peroxidation increased in a time depending manner in response to TNBS challenge. Conversely, the markers of the antioxidant pool, reduced glutathione (GSH) and catalase activity (CAT) were drastically reduced. Cur attenuated oxidative stress markers and partially restored CAT and GSH levels. Moreover, our results expanded the effect of Cur on TNBS-induced colonic mitochondrial dysfunction. In fact, TNBS induced mitochondrial swelling and lipids peroxidation. These events reflected in the opening of mitochondrial transition pore and could be an initial indication in the cascade process leading to cell death. TNBS inhibited also mitochondrial respiratory activity, caused overproduction of mitochondrial superoxide anion (O2-.) and reduced level of mitochondrial GSH. Nevertheless, Cur reduced the extent of mitochondrial oxidative stress induced by TNBS and restored colonic mitochondrial function. In conclusion, our results showed the critical role of oxidative stress in TNBS-induced colitis. They highlight the role of colonic mitochondrial dysfunction induced by TNBS, as a potential source of oxidative damages. Due to its potent antioxidant properties, Cur opens a promising therapeutic approach against oxidative inflammation in IBD.

Keywords: colitis, curcumin, mitochondria, oxidative stress, TNBS

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140 Characterising Rates of Renal Dysfunction and Sarcoidosis in Patients with Elevated Serum Angiotensin-Converting Enzyme

Authors: Fergal Fouhy, Alan O’Keeffe, Sean Costelloe, Michael Clarkson

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Background: Sarcoidosis is a systemic, non-infectious disease of unknown aetiology, characterized by non-caseating granulomatous inflammation. The lung is most often affected (90%); however, the condition can affect all organs, including the kidneys. There is limited evidence describing the incidence and characteristics of renal involvement in sarcoidosis. Serum angiotensin-converting enzyme (ACE) is a recognised biomarker used in the diagnosis and monitoring of sarcoidosis. Methods: A single-centre, retrospective cohort study of patients presenting to Cork University Hospital (CUH) in 2015 with first-time elevations of serum ACE was performed. This included an initial database review of ACE and other biochemistry results, followed by a medical chart review to confirm the presence or absence of sarcoidosis and management thereof. Acute kidney injury (AKI) was staged using the AKIN criteria, and chronic kidney disease (CKD) was staged using the KDIGO criteria. Follow-up was assessed over five years tracking serum creatinine, serum calcium, and estimated glomerular filtration rates (eGFR). Results: 119 patients were identified as having a first raised serum ACE in 2015. Seventy-nine male patients and forty female patients were identified. The mean age of patients identified was 47 years old. 11% had CKD at baseline. 18% developed an AKI at least once within the next five years. A further 6% developed CKD during this time period. 13% developed hypercalcemia. The patients within the lowest quartile of serums ACE had an incidence of sarcoidosis of 5%. None of this group developed hypercalcemia, 23% developed AKI, and 7% developed CKD. Of the patients with a serum ACE in the highest quartile, almost all had documented diagnoses of sarcoidosis with an incidence of 96%. 3% of this group developed hypercalcemia, 13% AKI and 3% developed CKD. Conclusions: There was an unexpectedly high incidence of AKI in patients who had a raised serum ACE. Not all patients with a raised serum ACE had a confirmed diagnosis of sarcoidosis. There does not appear to be a relationship between increased serum ACE levels and increased incidence of hypercalcaemia, AKI, and CKD. Ideally, all patients should have biopsy-proven sarcoidosis. This is an initial study that should be replicated with larger numbers and including multiple centres.

Keywords: sarcoidosis, acute kidney injury, chronic kidney disease, hypercalcemia

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139 Early Transcriptome Responses to Piscine orthoreovirus-1 in Atlantic salmon Erythrocytes Compared to Salmonid Kidney Cell Lines

Authors: Thomais Tsoulia, Arvind Y. M. Sundaram, Stine Braaen, Øyvind Haugland, Espen Rimstad, Øystein Wessel, Maria K. Dahle

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Fish red blood cells (RBC) are nucleated, and in addition to their function in gas exchange, they have been characterized as mediators of immune responses. Salmonid RBC are the major target cells of Piscineorthoreovirus (PRV), a virus associated with heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon. The activation of antiviral response genesin RBChas previously been described in ex vivo and in vivo PRV-infection models, but not explored in the initial virus encounter phase. In the present study, mRNA transcriptome responses were explored in erythrocytes from individual fish, kept ex vivo, and exposed to purified PRV for 24 hours. The responses were compared to responses in macrophage-like salmon head kidney (SHK-1) and endothelial-like Atlantic salmon kidney (ASK) cells, none of which support PRV replication. The comparative analysis showed that the antiviral response to PRV was strongest in the SHK-1 cells, with a set of 80 significantly induced genes (≥ 2-fold upregulation). In RBC, 46 genes were significantly upregulated, while ASK cells were not significantly responsive. In particular, the transcriptome analysis of RBC revealed that PRV significantly induced interferon regulatory factor 1 (IRF1) and interferon-induced protein with tetratricopeptide repeats 5-like (IFIT9). However, several interferon-regulated antiviral genes which have previously been reported upregulated in PRV infected RBC in vivo (myxovirus resistance (Mx), interferon-stimulated gene 15 (ISG15), toll-like receptor 3 (TLR3)), were not significantly induced after 24h of virus stimulation. In contrast to RBC, these antiviral response genes were significantly upregulated in SHK-1. These results confirm that RBC are involved in the innate immune response to viruses, but with a delayed antiviral response compared to SHK-1. A notable difference is that interferon regulatory factor 1 (IRF-1) is the most strongly induced gene in RBC, but not among the significantly induced genes in SHK-1. Putative differences in the binding, recognition, and response to PRV, and any link to effects on the ability of PRV to replicate remains to be explored.

Keywords: antiviral responses, atlantic salmon, piscine orthoreovirus-1, red blood cells, RNA-seq

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138 Dermatomyositis: It is Not Always an Allergic Reaction

Authors: Irfan Abdulrahman Sheth, Sohil Pothiawala

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Dermatomyositis is an idiopathic inflammatory myopathy, traditionally characterized by a progressive, symmetrical proximal muscle weakness and pathognomonic or characteristic cutaneous manifestations. We report a case of a 60-year old Chinese female who was referred from polyclinic for allergic rash over the body after applying hair dye 3 weeks ago. It was associated with puffiness of face, shortness of breath and hoarse voice since last 2 weeks with decrease effort tolerance. She also complained of dysphagia/ myalgia with progressive weakness of proximal muscles and palpitations. She denied chest pain, loss of appetite, weight loss, orthopnea or fever. She had stable vital signs and appeared cushingoid. She was noted to have rash over the scalp/ face and ecchymosis over the right arm with puffiness of face and periorbital oedema. There was symmetrical muscle weakness and other neurological examination was normal. Initial impression was of allergic reaction and underlying nephrotic syndrome and Cushing’s syndrome from TCM use. Diagnostic tests showed high Creatinine kinase (CK) of 1463 u/l, CK–MB of 18.7 ug/l and Troponin –T of 0.09 ug/l. The Full blood count and renal panel was normal. EMG showed inflammatory myositis. Patient was managed by rheumatologist and discharged on oral prednisolone with methotrexate/ ergocalciferol capsule and calcium carb, vitamin D tablets and outpatient follow up. In some patients, cutaneous disease exists in the absence of objective evidence of muscle inflammation. Management of dermatomyositis begins with careful investigation for the presence of muscle disease or of additional systemic involvement, particularly of the pulmonary, cardiac or gastrointestinal systems, and for the possibility of an accompanying malignancy. Muscle disease and systemic involvement can be refractory and may require multiple sequential therapeutic interventions or, at times, combinations of therapies. Thus, we want to highlight to the physicians that the cutaneous disease of dermatomyositis should not be confused with allergic reaction. It can be particularly challenging to diagnose. Early recognition aids appropriate management of this group of patients.

Keywords: dermatomyositis, myopathy, allergy, cutaneous disease

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137 Synthesis and Two-Photon Polymerization of a Cytocompatibility Tyramine Functionalized Hyaluronic Acid Hydrogel That Mimics the Chemical, Mechanical, and Structural Characteristics of Spinal Cord Tissue

Authors: James Britton, Vijaya Krishna, Manus Biggs, Abhay Pandit

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Regeneration of the spinal cord after injury remains a great challenge due to the complexity of this organ. Inflammation and gliosis at the injury site hinder the outgrowth of axons and hence prevent synaptic reconnection and reinnervation. Hyaluronic acid (HA) is the main component of the spinal cord extracellular matrix and plays a vital role in cell proliferation and axonal guidance. In this study, we have synthesized and characterized a photo-cross-linkable HA-tyramine (tyr) hydrogel from a chemical, mechanical, electrical, biological and structural perspective. From our experimentation, we have found that HA-tyr can be synthesized with controllable degrees of tyramine substitution using click chemistry. The complex modulus (G*) of HA-tyr can be tuned to mimic the mechanical properties of the native spinal cord via optimization of the photo-initiator concentration and UV exposure. We have examined the degree of tyramine-tyramine covalent bonding (polymerization) as a function of UV exposure and photo-initiator use via Photo and Nuclear magnetic resonance spectroscopy. Both swelling and enzymatic degradation assays were conducted to examine the resilience of our 3D printed hydrogel constructs in-vitro. Using a femtosecond 780nm laser, the two-photon polymerization of HA-tyr hydrogel in the presence of riboflavin photoinitiator was optimized. A laser power of 50mW and scan speed of 30,000 μm/s produced high-resolution spatial patterning within the hydrogel with sustained mechanical integrity. Using dorsal root ganglion explants, the cytocompatibility of photo-crosslinked HA-tyr was assessed. Using potentiometry, the electrical conductivity of photo-crosslinked HA-tyr was assessed and compared to that of native spinal cord tissue as a function of frequency. In conclusion, we have developed a biocompatible hydrogel that can be used for photolithographic 3D printing to fabricate tissue engineered constructs for neural tissue regeneration applications.

Keywords: 3D printing, hyaluronic acid, photolithography, spinal cord injury

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136 The Effect of a Probiotic Diet on htauE14 in a Rodent Model of Alzheimer’s Disease

Authors: C. Flynn, Q. Yuan, C. Reinhardt

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Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder affecting broad areas of the cerebral cortex and hippocampus. More than 95% of AD cases are representative of sporadic AD, where both genetic and environmental risk factors play a role. The main pathological features of AD include the widespread deposition of amyloid-beta and neurofibrillary tau tangles in the brain. The earliest brain pathology related to AD has been defined as hyperphosphorylated soluble tau in the noradrenergic locus coeruleus (LC) neurons, characterized by Braak. However, the cause of this pathology and the ultimate progression of AD is not understood. Increasing research points to a connection between the gut microbiota and the brain, and mounting evidence has shown that there is a bidirectional interaction between the two, known as the gut-brain axis. This axis can allow for bidirectional movement of neuroinflammatory cytokines and pathogenic misfolded proteins, as seen in AD. Prebiotics and probiotics have been shown to have a beneficial effect on gut health and can strengthen the gut-barrier as well as the blood-brain barrier, preventing the spread of these pathogens across the gut-brain axis. Our laboratory has recently established a pretangle tau rat model, in which we selectively express pseudo-phosphorylated human tau (htauE14) in the LC neurons of TH-Cre rats. LC htauE14 produced pathological changes in rats resembling those of the preclinical AD pathology (reduced olfactory discrimination and LC degeneration). In this work, we will investigate the effects of pre/probiotic ingestion on AD behavioral deficits, blood inflammation/cytokines, and various brain markers in our experimental rat model of AD. Rats will be infused with an adeno-associated viral vector containing a human tau gene pseudophosphorylated at 14 sites (common in LC pretangles) into 2-3 month TH-Cre rats. Fecal and blood samples will be taken at pre-surgery, and various post-surgery time points. A collection of behavioral tests will be performed, and immunohistochemistry/western blotting techniques will be used to observe various biomarkers. This work aims to elucidate the relationship between gut health and AD progression by strengthening gut-brain relationship and aims to observe the overall effect on tau formation and tau pathology in AD brains.

Keywords: alzheimer’s disease, aging, gut microbiome, neurodegeneration

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135 Ph-Triggered Cationic Solid Lipid Nanoparticles Mitigated Colitis in Mice

Authors: Muhammad Naeem, Juho Lee, Jin-Wook Yoo

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In this study, we hypothesized that prolonged gastrointestinal transit at the inflamed colon conferred by a pH-triggered mucoadhesive smart nanoparticulate drug delivery system aids in achieving selective and sustained levels of the drug within the inflamed colon for the treatment of ulcerative colitis. We developed budesonide-loaded pH-sensitive charge-reversal solid lipid nanoparticles (SLNs) using a hot homogenization method. Polyetylenimine (PEI) was used to render SLNs cationic (PEI-SLNs). Eudragit S100 (ES) was coated on PEI-SLNs for pH-trigger charge-reversal SLNs (ES-PEI-SLNs). Therapeutic potential of the prepared SNLs formulation was evaluated in ulcerative colitis in mice. The transmission electron microscopy, zeta size and zeta potential data showed the successful formation of SLNs formulations. SLNs and PEI-SLNs showed burst drug release in acidic pH condition mimicking stomach and early small intestine environment which limiting their application as oral delivery systems. However, ES-PEI-SLNs prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. Most importantly, the surface charge of ES-PEI-SLNs switched from negative to positive in colonic conditions by pH-triggered removal of ES coating and accumulated selectively in inflamed colon. Furthermore, a charge reversal ES-PEI-SLNs showed a superior mitigation of dextran sulfate sodium (DSS)-induced acute colitis in mice as compared to SLNs and PEI-SLNs treated groups. Moreover, histopathological analysis of distal colon sections stained with hematoxylin/eosin and E-cadherin immunostaining revealed attenuated inflammation in an ES-PEI-SLNs-treated group. We also found that ES-PEI-SLNs markedly reduced the myeloperoxidase level and expression of TNF-alpha in colon tissue. Our results suggest that the pH-triggered charge reversal SLNs presented in this study would be a promising approach for ulcerative colitis therapy.

Keywords: solid lipid nanoparticles, stimuli-triggered charge-reversal, ulcerative colitis, methacrylate copolymer, budesonide

Procedia PDF Downloads 248