Search results for: skin disease
2893 Numerical Solutions of Boundary Layer Flow over an Exponentially Stretching/Shrinking Sheet with Generalized Slip Velocity
Authors: Roslinda Nazar, Ezad Hafidz Hafidzuddin, Norihan M. Arifin, Ioan Pop
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In this paper, the problem of steady laminar boundary layer flow and heat transfer over a permeable exponentially stretching/shrinking sheet with generalized slip velocity is considered. The similarity transformations are used to transform the governing nonlinear partial differential equations to a system of nonlinear ordinary differential equations. The transformed equations are then solved numerically using the bvp4c function in MATLAB. Dual solutions are found for a certain range of the suction and stretching/shrinking parameters. The effects of the suction parameter, stretching/shrinking parameter, velocity slip parameter, critical shear rate, and Prandtl number on the skin friction and heat transfer coefficients as well as the velocity and temperature profiles are presented and discussed.Keywords: boundary layer, exponentially stretching/shrinking sheet, generalized slip, heat transfer, numerical solutions
Procedia PDF Downloads 4342892 Relationship between Matrilin-3 (MATN-3) Gene Single Nucleotide Six Polymorphism, Transforming Growth Factor Beta 2 and Radiographic Grading in Primary Osteoarthritis
Authors: Heba Esaily, Rawhia Eledl, Daila Aboelela, Rasha Noreldin
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Objective: Assess serum level of Transforming growth factor beta 2 (TGF-β2) and Matrilin-3 (MATN3) SNP6 polymorphism in osteoarthritic patients Background: Osteoarthritis (OA) is a musculoskeletal disease characterized by pain and joint stiffness. TGF-β 2 is involved in chondrogenesis and osteogenesis, It has found that MATN3 gene and protein expression was correlated with the extent of tissue damage in OA. Findings suggest that regulation of MATN3 expression is essential for maintenance of the cartilage extracellular matrix microenvironment Subjects and Methods: 72 cases of primary OA (56 with knee OA and 16 with generalized OA were compared with that of 18 healthy controls. Radiographs were scored with the Kellgren-Lawrence scale. Serum TGF-β2 was measured by using (ELISA), levels of marker were correlated to radiographic grading of disease and MATN3 SNP6 polymorphism was determined by (PCR-RFLP). Results: MATN3 SNP6 polymorphism and serum level of TGF-β2 were higher in OA compared with controls. Genotype, NN and N allele frequency were higher in patients with OA compared with controls. NN genotype and N allele frequency were higher in knee osteoarthritis than generalized OA. Significant positive correlation between level of TGFβ2 and radiographic grading in group with knee OA, but no correlation between serum level of TGFβ2 and radiographic grading in generalized OA. Conclusion: MATN3 SNP6 polymorphism and TGF-β2 implicated in the pathogenesis of osteoarthritis. Association of N/N genotype with primary osteoarthritis emphasizes on the need for prospective study include larger sample size to confirm the results of the present study.Keywords: Matrilin-3, transforming growth factor beta 2, primary osteoarthritis, knee osteoarthritis
Procedia PDF Downloads 2712891 Capturing the Stress States in Video Conferences by Photoplethysmographic Pulse Detection
Authors: Jarek Krajewski, David Daxberger
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We propose a stress detection method based on an RGB camera using heart rate detection, also known as Photoplethysmography Imaging (PPGI). This technique focuses on the measurement of the small changes in skin colour caused by blood perfusion. A stationary lab setting with simulated video conferences is chosen using constant light conditions and a sampling rate of 30 fps. The ground truth measurement of heart rate is conducted with a common PPG system. The proposed approach for pulse peak detection is based on a machine learning-based approach, applying brute force feature extraction for the prediction of heart rate pulses. The statistical analysis showed good agreement (correlation r = .79, p<0.05) between the reference heart rate system and the proposed method. Based on these findings, the proposed method could provide a reliable, low-cost, and contactless way of measuring HR parameters in daily-life environments.Keywords: heart rate, PPGI, machine learning, brute force feature extraction
Procedia PDF Downloads 1262890 Formal Models of Sanitary Inspections Teams Activities
Authors: Tadeusz Nowicki, Radosław Pytlak, Robert Waszkowski, Jerzy Bertrandt, Anna Kłos
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This paper presents methods for formal modeling of activities in the area of sanitary inspectors outbreak of food-borne diseases. The models allow you to measure the characteristics of the activities of sanitary inspection and as a result allow improving the performance of sanitary services and thus food security.Keywords: food-borne disease, epidemic, sanitary inspection, mathematical models
Procedia PDF Downloads 3082889 An Attempt of Cost Analysis of Heart Failure Patients at Cardiology Department at Kasr Al Aini Hospitals: A Micro-Costing Study from Social Perspective
Authors: Eman Elsebaie, A. Sedrak, R. Ziada
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Introduction: In the recent decades, heart failure (HF) has become one of the most prevalent cardio-vascular disease (CVDs), especially in the elderly and the main cause of hospitalization in Egypt cardiology departments. By 2030, the prevalence of HF is expected to increase by 25%. Total direct costs will increase to $818 billion, and the total indirect cost in terms of lost productivity is close to $275 billion. The current study was conducted to estimate the economic costs of services delivered for heart failure patients at the cardiology department in Cairo University Hospitals (CUHs). Aim: To gain an understanding of the cost of heart failure disease and its main drivers aiming to minimize associated health care costs. Subjects and Methods: Economic cost analysis study was conducted for a prospective group of all cases of HF admitted to the cardiology department in CUHs from end of March till end of April 2016 and another retrospective randomized sample from patients with HF, during the first 3 months of 2016 to measure estimated average cost per patient per day. Results: The mean age of the prospective group was 48.6 ± 17.16 years versus 52.3 ± 11.5 years for the retrospective group. The median (IQR) of Length of stay was 15 (15) days in the prospective group versus 9 (16) days in the retrospective group. The average HF inpatient cost/day in the cardiology department during April 2016 was 362.32 (255.5) L.E. versus 391.2(255.9) L.E. during January and February 2016. Conclusion: Up to 70% of expenditure in the management of HF is related to hospital admission. The average cost of such an admission was 5540.03 (IQR=7507.8) L.E. and 4687.4 (IQR=7818.8) L.E. with the average cost per day estimated at 362.32 (IQR=255.5) L.E. and 386.2(IQR=255.9) L.E. in prospective and retrospective groups respectively.Keywords: health care cost, heart failure, hospitalization, inpatient
Procedia PDF Downloads 2462888 Prognostic Impact of Pre-transplant Ferritinemia: A Survival Analysis Among Allograft Patients
Authors: Mekni Sabrine, Nouira Mariem
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Background and aim: Allogeneic hematopoietic stem cell transplantation is a curative treatment for several hematological diseases; however, it has a non-negligible morbidity and mortality depending on several prognostic factors, including pre-transplant hyperferritinemia. The aim of our study was to estimate the impact of hyperferritinemia on survivals and on the occurrence of post-transplant complications. Methods: It was a longitudinal study conducted over 8 years and including all patients who had a first allograft. The impact of pretransplant hyperferritinemia (ferritinemia ≥1500) on survivals was studied using the Kaplan Meier method and the COX model for uni- and multivariate analysis. The Khi-deux test and binary logistic regression were used to study the association between pretransplant ferritinemia and post-transplant complications. Results: One hundred forty patients were included with an average age of 26.6 years and a sex ratio (M/F)=1.4. Hyperferritinemia was found in 33% of patients. It had no significant impact on either overall survival (p=0.9) or event -free survival (p=0.6). In multivariate analysis, only the type of disease was independently associated with overall survival (p=0.04) and event-free survival (p=0.002). For post-allograft complications: The occurrence of early documented infections was independently associated with pretransplant hyperferritinemia (p=0.02) and the presence of acute graft versus host disease( GVHD) (p<10-3). The occurrence of acute GVHD was associated with early documented infection (p=0.002) and Cytomegalovirus reactivation (p<10-3). The occurrence of chronic GVHD was associated with the presence of Cytomegalovirus reactivation (p=0.006) and graft source (p=0.009). Conclusion: Our study showed the significant impact of pre-transplant hyperferritinemia on the occurrence of early infections but not on survivals. Early and more accurate assessment iron overload by other tests such as liver magnetic resonance imaging with initiation of chelating treatment could prevent the occurrence of such complications after transplantation.Keywords: allogeneic, transplants, ferritin, survival
Procedia PDF Downloads 702887 Application of Pedicled Perforator Flaps in Large Cavities of the Breast
Authors: Neerja Gupta
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Objective-Reconstruction of large cavities of the breast without contralateral symmetrisation Background- Reconstruction of breast includes a wide spectrum of procedures from displacement to regional and distant flaps. The pedicled Perforator flaps cover a wide spectrum of reconstruction surgery for all quadrants of the breast, especially in patients with comorbidities. These axial flaps singly or adjunct are based on a near constant perforator vessel, a ratio of 2:1 at its entry in a flap is good to maintain vascularity. The perforators of lateral chest wall viz LICAP, LTAP have overlapping perfurosomes without clear demarcation. LTAP is localized in the narrow zone between the lateral breast fold and anterior axillary line,2.5-3.8cm from the fold. MICAP are localized at 1-2 cm from sternum. Being 1-2mm in diameter, a Single perforator is good to maintain the flap. LICAP has a dominant perforator in 6th-11th spaces, while LTAP has higher placed dominant perforators in 4th and 5th spaces. Methodology-Six consecutive patients who underwent reconstruction of the breast with pedicled perforator flaps were retrospectively analysed. Selections of the flap was done based on the size and locations of the tumour, anticipated volume loss, willingness to undergo contralateral symmetrisation, cosmetic expectations, and finances available.3 patients underwent vertical LTAP, the distal limit of the flap being the inframammary crease. 3 patients underwent MICAP, oriented along the axis of rib, the distal limit being the anterior axillary line. Preoperative identification was done using a unidirectional hand held doppler. The flap was raised caudal to cranial, the pivot point of rotation being the vessel entry into the skin. The donor area is determined by the skin pinch. Flap harvest time was 20-25 minutes. Intra operative vascularity was assessed with dermal bleed. The patient immediate pre, post-operative and follow up pics were compared independently by two breast surgeons. Patients were given a breast Q questionnaire (licensed) for scoring. Results-The median age of six patients was 46. Each patient had a hospital stay of 24 hours. None of the patients was willing for contralateral symmetrisation. The specimen dimensions were from 8x6.8x4 cm to 19x16x9 cm. The breast volume reconstructed range was 30 percent to 45 percent. All wide excision had free margins on frozen. The mean flap dimensions were 12x5x4.5 cm. One LTAP underwent marginal necrosis and delayed wound healing due to seroma. Three patients were phyllodes, of which one was borderline, and 2 were benign on final histopathology. All other 3 patients were invasive ductal cancer and have completed their radiation. The median follow up is 7 months the satisfaction scores at median follow of 7 months are 90 for physical wellbeing and 85 for surgical results. Surgeons scored fair to good in Harvard score. Conclusion- Pedicled perforator flaps are a valuable option for 3/8th volume of breast defects. LTAP is preferred for tumours at the Central, upper, and outer quadrants of the breast and MICAP for the inner and lower quadrant. The vascularity of the flap is dependent on the angiosomalterritories; adequate venous and cavity drainage.Keywords: breast, oncoplasty, pedicled, perforator
Procedia PDF Downloads 1892886 Comparative Vector Susceptibility for Dengue Virus and Their Co-Infection in A. aegypti and A. albopictus
Authors: Monika Soni, Chandra Bhattacharya, Siraj Ahmed Ahmed, Prafulla Dutta
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Dengue is now a globally important arboviral disease. Extensive vector surveillance has already established A.aegypti as a primary vector, but A.albopictus is now accelerating the situation through gradual adaptation to human surroundings. Global destabilization and gradual climatic shift with rising in temperature have significantly expanded the geographic range of these species These versatile vectors also host Chikungunya, Zika, and yellow fever virus. Biggest challenge faced by endemic countries now is upsurge in co-infection reported with multiple serotypes and virus co-circulation. To foster vector control interventions and mitigate disease burden, there is surge for knowledge on vector susceptibility and viral tolerance in response to multiple infections. To address our understanding on transmission dynamics and reproductive fitness, both the vectors were exposed to single and dual combinations of all four dengue serotypes by artificial feeding and followed up to third generation. Artificial feeding observed significant difference in feeding rate for both the species where A.albopictus was poor artificial feeder (35-50%) compared to A.aegypti (95-97%) Robust sequential screening of viral antigen in mosquitoes was followed by Dengue NS1 ELISA, RT-PCR and Quantitative PCR. To observe viral dissemination in different mosquito tissues Indirect immunofluorescence assay was performed. Result showed that both the vectors were infected initially with all dengue(1-4)serotypes and its co-infection (D1 and D2, D1 and D3, D1 and D4, D2 and D4) combinations. In case of DENV-2 there was significant difference in the peak titer observed at 16th day post infection. But when exposed to dual infections A.aegypti supported all combinations of virus where A.albopictus only continued single infections in successive days. There was a significant negative effect on the fecundity and fertility of both the vectors compared to control (PANOVA < 0.001). In case of dengue 2 infected mosquito, fecundity in parent generation was significantly higher (PBonferroni < 0.001) for A.albopicus compare to A.aegypti but there was a complete loss of fecundity from second to third generation for A.albopictus. It was observed that A.aegypti becomes infected with multiple serotypes frequently even at low viral titres compared to A.albopictus. Possible reason for this could be the presence of wolbachia infection in A.albopictus or mosquito innate immune response, small RNA interference etc. Based on the observations it could be anticipated that transovarial transmission may not be an important phenomenon for clinical disease outcome, due to the absence of viral positivity by third generation. Also, Dengue NS1 ELISA can be used for preliminary viral detection in mosquitoes as more than 90% of the samples were found positive compared to RT-PCR and viral load estimation.Keywords: co-infection, dengue, reproductive fitness, viral quantification
Procedia PDF Downloads 2092885 Ethical Considerations in In-Utero Gene Editing
Authors: Shruti Govindarajan
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In-utero gene editing with CRISPR-Cas9 opens up new possibilities for treating genetic disorders during pregnancy while still in mother’s womb. By targeting genetic mutations in the early stages of fetal development, this approach could potentially prevent severe conditions—like cystic fibrosis, sickle cell anemia, and muscular dystrophy—from causing harm. CRISPR-Cas9, which allows precise DNA edits, could be delivered into fetal cells through vectors such as adeno-associated viruses (AAVs) or nanoparticles, correcting disease-causing mutations and possibly offering lifelong relief from these disorders. For families facing severe genetic diagnoses, in-utero gene editing could provide a transformative option. However, technical challenges remain, including ensuring that gene editing only targets the intended cells and verifying long-term safety. Ethical considerations are also at the forefront of this technology. The editing of a fetus's genes brings up difficult questions about consent, especially since these genetic changes will affect the child’s entire life without their input. There's also concern over possible unintended side effects, or changes passed down to future generations. Moreover, if used beyond therapeutic purposes, this technology could be misused for ‘enhancements,’ like selecting for certain physical or cognitive traits, raising concerns about inequality and social pressures. In this way, in-utero gene editing brings both exciting potential and complex moral questions. As research progresses, addressing these scientific and ethical concerns will be key to ensuring that this technology is used responsibly, prioritizing safety, fairness, and a focus on alleviating genetic disease. A cautious and inclusive approach, along with clear regulations, will be essential to realizing the benefits of in-utero gene editing while protecting against unintended consequences.Keywords: in-utero gene editing, CRISPR, bioethics, genetic disorder
Procedia PDF Downloads 172884 Insights into Insect Vectors: Liberibacter Interactions
Authors: Murad Ghanim
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The citrus greening disease, also known as Huanglongbing, caused by the phloem-limited bacterium Candidatus Liberibacter asiaticus (CLas) has resulted in tremendous losses and the death of millions of citrus trees worldwide. CLas is transmitted by the Asian citrus psyllid (ACP) Diaphorina citri. The closely-related bacterium Candidatus Liberibacter solanacearum (CLso), which is associated with vegetative disorders in carrots and the zebra chips disease in potatoes, is transmitted by other psyllid species including Bactericera trigonica in carrots and B. ckockerelli in potatoes. Chemical sprays are currently the prevailing method for managing these diseases for limiting psyllid populations; however, they are limited in their effectiveness. A promising approach to prevent the transmission of these pathogens is to interfere with the vector-pathogen interactions, but our understanding of these processes is very limited. CLas induces changes in the nuclear architecture in the midgut of ACP and activates programmed cell death (apoptosis) in this organ. Strikingly, CLso displayed an opposite effect in the gut of B. trigonica, showing limited apoptosis, but widespread necrosis. Electron and fluorescent microscopy further showed that CLas induced the formation of Endoplasmic reticulum (ER) inclusion- and replication-like bodies, in which it increases and multiplies. ER involvement in bacterial replication is hypothesized to be the first stage of an immune response leading to the apoptotic and necrotic responses. ER exploitation and the subsequent events that lead to these cellular and stress responses might activate a cascade of molecular responses ending up with apoptosis and necrosis. Understanding the molecular interactions that underlay the necrotic/apoptotic responses to the bacteria will increase our knowledge of ACP-CLas, and BT-CLso interactions, and will set the foundation for developing novel, and efficient strategies to disturb these interactions and inhibit the transmission.Keywords: Liberibacter, psyllid, transmission, apoptosis, necrosis
Procedia PDF Downloads 1482883 Total Phenols, Total Flavonoids Contents and Free Radical Scavenging Activity of Seeds Extracts of Lawsonia alba (henna) from Algeria
Authors: Rekia. Cherbi, Mokhtar. Saidi, Mohamed. Yousfi, Zhor. Rahmani
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Lawsonia alba (Henna) is widely used in folkloric medicinal for a treatment of various skin diseases such as Eczema (atopic dermatitis), boils and sores. The aim of the present study is to determine the antioxidant activity, total phenolics, flavonoids, and condensed tannins content of extracts from the seeds of Lawsonia. alba grown in Algeria and selected from three different regions (Adrar, Biskra, and Ouargla). Total phenolics content ranged from 68,42 ± 0,54 to 88,31 ± 0,78mg gallic acid equivalents (GAE)/g dry weight, the flavonoids content varied from 1,13 ± 0,0035 to 1,367 ± 0,002mg quercetin equivalents (Q)/ g dry weight and condensed tannins (14,47 ± 0,138 to 25,50 ± 0,076 mg catechin equivalents (CE)/g dry weight). The antioxidant activities of the extracts were evaluated by DPPH assay. The results showed that all extracts from the seeds of Lawsonia. alba seem to be good trappers of radicals, the IC50 values of the extracts ranged between 0,00826 and 0,01 g/l.Keywords: antioxidant activity, Lawsonia. alba, phenolic compounds, seeds
Procedia PDF Downloads 3492882 Restoring Sagging Neck with Minimal Scar Face Lifting
Authors: Alessandro Marano
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The author describes the use of deep plane face lifting and platysmaplasty to treat sagging neck with minimal scars. Series of case study. The author uses a selective deep plane face lift with a minimal access scar that not extend behind the ear lobe, neck liposuction and platysmaplasty to restore the sagging neck; the scars are minimal and no require drainage post-op. The deep plane face lifting can achieve a good result restoring vertical vectors in aging and sagging face, neck district can be treated without cutting the skin behind the ear lobe combining the SMAS vertical suspension and platysmaplasty; surgery can be performed in local anesthesia with sedation in day surgery and fast recovery. Restoring neck sagging without extend scars behind ear lobe is possible in selected patients, procedure is fast, safe, no drainage required, patients are satisfied and healing time is fast and comfortable.Keywords: face lifting, aesthetic, face, neck, platysmaplasty, deep plane
Procedia PDF Downloads 1052881 Evaluation of the Gamma-H2AX Expression as a Biomarker of DNA Damage after X-Ray Radiation in Angiography Patients
Authors: Reza Fardid, Aliyeh Alipour
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Introduction: Coronary heart disease (CHD) is the most common and deadliest diseases. A coronary angiography is an important tool for the diagnosis and treatment of this disease. Because angiography is performed by exposure to ionizing radiation, it can lead to harmful effects. Ionizing radiation induces double-stranded breaks in DNA, which is a potentially life-threatening injury. The purpose of the present study is an investigation of the phosphorylation of histone H2AX in the location of the double-stranded break in Peripheral blood lymphocytes as an indication of Biological effects of radiation on angiography patients. Materials and Methods: This method is based on measurement of the phosphorylation of histone (gamma-H2AX, gH2AX) level on serine 139 after formation of DNA double-strand break. 5 cc of blood from 24 patients with angiography were sampled before and after irradiation. Blood lymphocytes were removed, fixed and were stained with specific ϒH2AX antibodies. Finally, ϒH2AX signal as an indicator of the double-strand break was measured with Flow Cytometry Technique. Results and discussion: In all patients, an increase was observed in the number of breaks in double-stranded DNA after irradiation (20.15 ± 14.18) compared to before exposure (1.52 ± 0.34). Also, the mean of DNA double-strand break was showed a linear correlation with DAP. However, although induction of DNA double-strand breaks associated with radiation dose in patients, the effect of individual factors such as radiosensitivity and regenerative capacity should not be ignored. If in future we can measure DNA damage response in every patient angiography and it will be used as a biomarker patient dose, will look very impressive on the public health level. Conclusion: Using flow cytometry readings which are done automatically, it is possible to detect ϒH2AX in the number of blood cells. Therefore, the use of this technique could play a significant role in monitoring patients.Keywords: coronary angiography, DSB of DNA, ϒH2AX, ionizing radiation
Procedia PDF Downloads 1912880 Characterization of the Physical Properties of Sheep Wool Fiber in Amhara National Regional State
Authors: Erkihun Zelalem
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Ethiopian’s sheep population, estimated to be 25.5 million heads, is found widely distributed across the diverse agro-ecological zones of the country. In the past, there were many projects that done to improve production of meat, milk and productivity of sheep breed. However, no significance research has been done so far on production of wool fiber in Ethiopia which could be taken as a potential fiber next to cotton. The measurement of the sheep wool fiber physical properties is critically important, technical, commercial and certification point of view. A total of 24 sheep from different breeds (Menz, Tikur, Farta and Washera) were used in this study. Samples of fiber were analyzed using standard measurements for wool fiber length (WFL), mean fiber diameter (MFD), coefficient of variation of wool fiber diameter (FDCV), breaking strength, elongation, crimp, cleanness and moisture content. Based on the result all parameters shows that there is a great potential of getting of wool fiber from the skin of sheep and according to the standards of its property and grading system based on wool fiber fineness is medium to course. These types of fibers can be making carpets, blankets, rugs, coverings and other products.Keywords: Fiber, Fineness, Carpet, Fleece, Raw Wool
Procedia PDF Downloads 1692879 Hematuria Following Magnesium Sulfate Administration in a Pregnant Patient with Renal Tubular Acidosis
Authors: Jan Gayl Barcelon, N. Gorgonio
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Renal tubular acidosis, a medical condition that involves the accumulation of acid in the body due to failure of the kidneys to maintain normal urine and blood pH, is rarely encountered in pregnancy. The effect of renal tubular acidosis in pregnancy is not fully established. It may worsen during pregnancy and cause maternal and fetal morbidity. A 30-year-old primigravida was diagnosed with renal tubular acidosis at age 7, but due to uncontrolled disease progression, she developed rickets at age 10. She was first seen in our institution at eight weeks gestation and maintained on bicarbonate and potassium supplementation. At 26 weeks gestation, she was diagnosed with polyhydramnios, causing on and off irregular uterine contractions. At 30 weeks gestation, despite oral Nifedipine, premature labor was uncontrolled; hence she was admitted for tocolysis. With elevated creatinine (123 umol/L) and a normal blood urea nitrogen level (6.70 mmol/L), she was referred to Nephrology Service, which cleared the patient prior to MgSO₄ drip. Dosing of 4g MgSO₄ over 20 minutes followed by a maintenance of 2g/hour x 24 hours for neuroprotection and tocolysis was ordered. Two hours after MgSO₄ drip initiation, hematuria developed with adequate urine output. The infusion was immediately stopped. The serum magnesium level was high normal at 6.7 mEq/L. After 4 hours of renal clearance, the repeat serum magnesium level was normal (2.7 mEq/L) and with clear urine output. The patient was then given Nifedipine 30mg/tab, 3x a day which controlled the uterine contractions. At 37 weeks gestation, the patient delivered via primary low transverse Cesarean Section to a live female with a birthweight of 2470gm, appropriate for gestational age. The use of MgSO₄ for the control of premature labor in patients with chronic renal disease secondary to renal tubular can cause hematuria.Keywords: hematuria, magnesium sulfate, premature labor, renal tubular acidosis
Procedia PDF Downloads 1332878 Causes of Death in Neuromuscular Disease Patients: 15-Year Experience in a Tertiary Care Hospital
Authors: Po-Ching Chou, Wen-Chen Liang, I. Chen Chen, Jong-Hau Hsu, Yuh-Jyh Jong
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Background:Cardiopulmonary complications seem to cause high morbidity and mortality in patients with neuromuscular diseases (NMD) but so far there is no domestic data reported in Taiwan. We, therefore attempted to analyze the factors to cause the death in NMD patients from our cohort. Methods:From 1998 to 2013, we retrospectively collected the information of the NMD patients treated and followed up in Kaohsiung Medical University Hospital. Forty-two patients with NMD who expired during these fifteen years were enrolled. The medical records of these patients were reviewed and the causes of death and the associated affecting factors were analyzed. Results:Eighteen patients with NMD (mean age=13.3, SD=12.4) with complete medical record and detailed information were finally included in this study, including spinal muscular atrophy (SMA) (n=9, 7/9: type 1), Duchenne muscular dystrophy (n=6), congenital muscular dystrophy (n=1), carnitine acyl-carnitine translocase (CACT) deficiency (n=1) and spinal muscular atrophy with respiratory distress (SMARD)(n=1). The place of death was in ICU (n=11, 61%), emergency room (n=3, 16.6%) or home (n=4, 22.2%). For SMA type 1 patients, most of them (71.4%, 5/7) died in emergency room or home and the other two expired during an ICU admission. The causes of death included acute respiratory failure due to pneumonia (n=13, 72.2 %), ventilator failure or dislocation (n=2, 11.1%), suffocation/choking (n=2, 11.1%), and heart failure with hypertrophic cardiomyopathy (n=1, 5.55%). Among the 15 patients died of respiratory failure or choking, 73.3% of the patients (n=11) received no ventilator care at home. 80% of the patients (n=12) received no cough assist at home. The patient died of cardiomyopathy received no medications for heart failure until the last admission. Conclusion: Respiratory failure and choking are the leading causes of death in NMD patients. Appropriate respiratory support and airway clearance play the critical role to reduce the mortality.Keywords: neuromuscular disease, cause of death, tertiary care hospital, medical sciences
Procedia PDF Downloads 5342877 A Replicon-Baculovirus Model for Efficient Packaging of Hepatitis E Virus RNA and Production of Infectious Virions
Authors: Mohammad K. Parvez, Mohammed S. Al-Dosari
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Hepatitis E virus (HEV) is an emerging RNA virus that causes acute and chronic liver disease with a global mortality rate of about 2%. Despite milestone developments in understanding of HEV biology, there is still lack of a robust culture system or animal model. Therefore, in a novel approach, two recombinant-baculoviruses (vBac-ORF2 and vBac-ORF3) that could overexpress HEV ORF2 (structural/capsid) and ORF3 (nonstructural/regulatory) proteins, respectively were constructed. The established HEV-SAR55 (genotype 1) replicon that contained GFP gene, in place of ORF2/ORF3 sequences was in vitro transcribed, and GFP production in RNA transfected S10-3 cells was scored by FACS. Enhanced infectivity, if any, of nascent virions produced by exogenously-supplied ORF2 and viral RNA by co-expression of ORF3 was tested on naïve HepG2 cells. Co-transduction with vBac-ORF2/vBac-ORF3 (108 pfu/microL) produced high amounts of native ORF2/ORF3 in approximately 60% of S10-3 cells, determined by immunofluorescence microscopy and Western analysis. FACS analysis showed about 9% GFP positivity of S10-3 cells on day6 post-transfection (i.e, day5 post-transduction). Further, FACS scoring indicated that lysates from S10-3 cultures receiving the RNA plus vBac-ORF2 were capable of producing HEV particles with about 4% infectivity in HepG2 cells. However, lysates of cultures co-transduced with vBac-ORF3, were found to further enhance virion infectivity by approximately 17%. This supported a previously proposed role of ORF3 as a minor-structural protein in HEV virion assembly and infectivity. In conclusion, the present model for efficient genomic RNA packaging and production of infectious virions could be a valuable tool to study various aspects of HEV molecular biology, in vitro.Keywords: chronic liver disease, hepatitis E virus, ORF2, ORF3, replicon
Procedia PDF Downloads 2582876 Improvement in Safety Profile of Semecarpus Anacardium Linn by Shodhana: An Ayurvedic Purification Method
Authors: Umang H. Gajjar, K. M. Khambholja, R. K. Patel
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Semecarpus anacardium shows the presence of bioflavonoids, phenolic compounds, bhilawanols, minerals, vitamins and amino acids. Detoxified S. anacardium and its oils are considered to have anti-inflammatory properties and used in nervous debility, neuritis, rheumatism and leprous modules. S. anacardium if used without purification causes toxic skin inflammation problem because it contains toxic phenolic oil. During this Shodhana Process - An ayurvedic purification method, toxic phenolic oil was removed, have marked effect on the concentration of the phytoconstituent & antioxidant activity of S. anacardium. Total phenolic content decreased up to 70 % (from 28.9 %w/w to 8.94 %w/w), while there is a negligible effect on the concentration of total flavonoid (7.51 %w/w to 7.43 %w/w) and total carbohydrate (0.907 %w/w to 0.853 % w/w) content. IC50& EC50 value of extract of S. anacardium before and after purification are 171.7 & 314.3 while EC50values are 280.μg/ml & 304. μg/ml, shows that antioxidant activity of S. anacardium is decreased but the safety profile of the drug is increased as the toxic phenolic oil was removed during Shodhana - An ayurvedic purification method.Keywords: Semecarpus anacardium, Shodhana process, safety profile, improvement
Procedia PDF Downloads 2602875 DSF Elements in High-Rise Timber Buildings
Authors: Miroslav Premrov, Andrej Štrukelj, Erika Kozem Šilih
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The utilization of prefabricated timber-wall elements with double glazing, called as double-skin façade element (DSF), represents an innovative structural approach in the context of new high-rise timber construction, simultaneously combining sustainable solutions with improved energy efficiency and living quality. In addition to the minimum energy needs of buildings, the design of modern buildings is also increasingly focused on the optimal indoor comfort, in particular on sufficient natural light indoors. An optimally energy-designed building with an optimal layout of glazed areas around the building envelope represents a great potential in modern timber construction. Usually, all these transparent façade elements, because of energy benefits, are primary asymmetrical oriented and if they are considered as non-resisting against a horizontal load impact, a strong torsion effects in the building can appear. The problem of structural stability against a strong horizontal load impact of such modern timber buildings especially increase in a case of high-rise structures where additional bracing elements have to be used. In such a case, special diagonal bracing systems or other bracing solutions with common timber wall elements have to be incorporated into the structure of the building to satisfy all prescribed resisting requirements given by the standards. However, all such structural solutions are usually not environmentally friendly and also not contribute to an improved living comfort, or they are not accepted by the architects at all. Consequently, it is a special need to develop innovative load-bearing timber-glass wall elements which are in the same time environmentally friendly, can increase internal comfort in the building, but are also load-bearing. The new developed load-bearing DSF elements can be a good answer on all these requirements. Timber-glass façade elements DSF wall elements consist of two transparent layers, thermal-insulated three-layered glass pane on the internal side and an additional single-layered glass pane on the external side of the wall. The both panes are separated by an air channel which can be of any dimensions and can have a significant influence on the thermal insulation or acoustic response of such a wall element. Most already published studies on DSF elements primarily deal only with energy and LCA solutions and do not address any structural problems. In previous studies according to experimental analysis and mathematical modeling it was already presented a possible benefit of such load-bearing DSF elements, especially comparing with previously developed load-bearing single-skin timber wall elements, but they were not applicate yet in any high-rise timber structure. Therefore, in the presented study specially selected 10-storey prefabricated timber building constructed in a cross-laminated timber (CLT) structural wall system is analyzed using the developed DSF elements in a sense to increase a structural lateral stability of the whole building. The results evidently highlight the importance the load-bearing DSF elements, as their incorporation can have a significant impact on the overall behavior of the structure through their influence on the stiffness properties. Taking these considerations into account is crucial to ensure compliance with seismic design codes and to improve the structural resilience of high-rise timber buildings.Keywords: glass, high-rise buildings, numerical analysis, timber
Procedia PDF Downloads 502874 ATR-IR Study of the Mechanism of Aluminum Chloride Induced Alzheimer Disease - Curative and Protective Effect of Lepidium sativum Water Extract on Hippocampus Rats Brain Tissue
Authors: Maha J. Balgoon, Gehan A. Raouf, Safaa Y. Qusti, Soad S. Ali
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The main cause of Alzheimer disease (AD) was believed to be mainly due to the accumulation of free radicals owing to oxidative stress (OS) in brain tissue. The mechanism of the neurotoxicity of Aluminum chloride (AlCl3) induced AD in hippocampus Albino wister rat brain tissue, the curative & the protective effects of Lipidium sativum group (LS) water extract were assessed after 8 weeks by attenuated total reflection spectroscopy ATR-IR and histologically by light microscope. ATR-IR results revealed that the membrane phospholipid undergo free radical attacks, mediated by AlCl3, primary affects the polyunsaturated fatty acids indicated by the increased of the olefinic -C=CH sub-band area around 3012 cm-1 from the curve fitting analysis. The narrowing in the half band width(HBW) of the sνCH2 sub-band around 2852 cm-1 due to Al intoxication indicates the presence of trans form fatty acids rather than gauch rotomer. The degradation of hydrocarbon chain to shorter chain length, increasing in membrane fluidity, disorder and decreasing in lipid polarity in AlCl3 group were indicated by the detected changes in certain calculated area ratios compared to the control. Administration of LS was greatly improved these parameters compared to the AlCl3 group. Al influences the Aβ aggregation and plaque formation, which in turn interferes to and disrupts the membrane structure. The results also showed a marked increase in the β-parallel and antiparallel structure, that characterize the Aβ formation in Al-induced AD hippocampal brain tissue, indicated by the detected increase in both amide I sub-bands around 1674, 1692 cm-1. This drastic increase in Aβ formation was greatly reduced in the curative and protective groups compared to the AlCl3 group and approaches nearly the control values. These results were supported too by the light microscope. AlCl3 group showed significant marked degenerative changes in hippocampal neurons. Most cells appeared small, shrieked and deformed. Interestingly, the administration of LS in curative and protective groups markedly decreases the amount of degenerated cells compared to the non-treated group. Also the intensity of congo red stained cells was decreased. Hippocampal neurons looked more/or less similar to those of control. This study showed a promising therapeutic effect of Lipidium sativum group (LS) on AD rat model that seriously overcome the signs of oxidative stress on membrane lipid and restore the protein misfolding.Keywords: aluminum chloride, alzheimer disease, ATR-IR, Lipidium sativum
Procedia PDF Downloads 3692873 DEKA-1 a Dose-Finding Phase 1 Trial: Observing Safety and Biomarkers using DK210 (EGFR) for Inoperable Locally Advanced and/or Metastatic EGFR+ Tumors with Progressive Disease Failing Systemic Therapy
Authors: Spira A., Marabelle A., Kientop D., Moser E., Mumm J.
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Background: Both interleukin-2 (IL-2) and interleukin-10 (IL-10) have been extensively studied for their stimulatory function on T cells and their potential to obtain sustainable tumor control in RCC, melanoma, lung, and pancreatic cancer as monotherapy, as well as combination with PD-1 blockers, radiation, and chemotherapy. While approved, IL-2 retains significant toxicity, preventing its widespread use. The significant efforts undertaken to uncouple IL-2 toxicity from its anti-tumor function have been unsuccessful, and early phase clinical safety observed with PEGylated IL-10 was not met in a blinded Phase 3 trial. Deka Biosciences has engineered a novel molecule coupling wild-type IL-2 to a high affinity variant of Epstein Barr Viral (EBV) IL-10 via a scaffold (scFv) that binds to epidermal growth factor receptors (EGFR). This patented molecule, termed DK210 (EGFR), is retained at high levels within the tumor microenvironment for days after dosing. In addition to overlapping and non-redundant anti-tumor function, IL-10 reduces IL-2 mediated cytokine release syndrome risks and inhibits IL-2 mediated T regulatory cell proliferation. Methods: DK210 (EGFR) is being evaluated in an open-label, dose-escalation (Phase 1) study with 5 (0.025-0.3 mg/kg) monotherapy dose levels and (expansion cohorts) in combination with PD-1 blockers, or radiation or chemotherapy in patients with advanced solid tumors overexpressing EGFR. Key eligibility criteria include 1) confirmed progressive disease on at least one line of systemic treatment, 2) EGFR overexpression or amplification documented in histology reports, 3) at least a 4 week or 5 half-lives window since last treatment, and 4) excluding subjects with long QT syndrome, multiple myeloma, multiple sclerosis, myasthenia gravis or uncontrolled infectious, psychiatric, neurologic, or cancer disease. Plasma and tissue samples will be investigated for pharmacodynamic and predictive biomarkers and genetic signatures associated with IFN-gamma secretion, aiming to select subjects for treatment in Phase 2. Conclusion: Through successful coupling of wild-type IL-2 with a high affinity IL-10 and targeting directly to the tumor microenvironment, DK210 (EGFR) has the potential to harness IL-2 and IL-10’s known anti-cancer promise while reducing immunogenicity and toxicity risks enabling safe concomitant cytokine treatment with other anti-cancer modalities.Keywords: cytokine, EGFR over expression, interleukine-2, interleukine-10, clinical trial
Procedia PDF Downloads 902872 Transient/Steady Natural Convective Flow of Reactive Viscous Fluid in Vertical Porous Pipe
Authors: Ahmad K. Samaila, Basant K. Jha
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This paper presents the effects of suction/injection of transient/steady natural convection flow of reactive viscous fluid in a vertical porous pipe. The mathematical model capturing the time dependent flow of viscous reactive fluid is solved using implicit finite difference method while the corresponding steady state model is solved using regular perturbation technique. Results of analytical and numerical solutions are reported for various parametric conditions to illustrate special features of the solutions. The coefficient of skin friction and rate of heat transfer are obtained and illustrated graphically. The numerical solution is shown to be in excellent agreement with the closed form analytical solution. It is interesting to note that time required to reach steady state is higher in case of injection in comparison to suction.Keywords: porous pipe, reactive viscous fluid, transient natural-convective flow, analytical solution
Procedia PDF Downloads 2992871 Mechanism of Modeling the Level of Bcr-Abl Oncoprotein by Ubiquitin-Proteasome System in Chronic Myeloid Leukemia
Authors: Svitlana Antonenko, Gennady Telegeev
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Introductive statement: The development of chronic myeloid leukemia (CML) is caused by Bcr-Abl oncoprotein. Modern treatments with tyrosine kinase inhibitors are greatly complicated by the mutational variability of the Bcr-Abl oncoprotein, which causes drug resistance. Therefore, there is an urgent need to develop new approaches to the treatment of the disease, which will allow modeling the level of Bcr-Abl oncoprotein in the cell. Promising in this direction is the identification of proteases that can selectively promote cellular proteolysis of oncoproteins. The aim of the study was to study the effect of the interaction of Bcr-Abl with deubiquitinase USP1 on the level of oncoprotein in CML cells. Methodology: K562 cells were selected for the experiment. Сells were incubated with ML323 inhibitor for 24 hours. Precipitation of endogenous proteins from K562 cell lysate was performed using anti-Bcr-Abl antibodies. Cell lysates and precipitation results were studied by Western blot. Subcellular localization of proteins was studied by immunofluorescence analysis followed by confocal microscopy. The results were analyzed quantitatively and statistically. Major findings: The Bcr-Abl/USP1 protein complex was detected in CML cells, and it was found that inhibition of USP1 deubiquitinating activity by the compound ML323 leads to disruption of this protein complex and a decrease in the level of Bcr-Abl oncoprotein in cells. The interaction of Bcr-Abl with USP1 may result in deubiquitination of the oncoprotein, which disrupts its proteasomal degradation and leads to the accumulation of CML in cells. Conclusion: We believe that the interaction of oncoprotein with USP1 may be one of the prerequisites that contribute to malignant cell transformation due to the deubiquitination of oncoprotein, which leads to its accumulation and disease progression. A correlation was found between the deubiquitinating activity of USP1 and the level of oncoprotein in CML cells. Thus, we identify deubiquitinase USP1 as a promising therapeutic target for the development of a new strategy for the treatment of CML by modulating the level of Bcr-Abl in the cell.Keywords: chronic myeloid leukemia, Bcr-Abl, USP1, deubiquitination Bcr-Abl, K562 cell
Procedia PDF Downloads 722870 Comparative Evaluation of the Effectiveness of Different Mindfulness-Based Interventions on Medically Unexplained Symptoms: A Systematic Review
Authors: R. R. Billones, N. Lukkahatai, L. N. Saligan
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Mindfulness based interventions (MBIs) have been used in medically unexplained symptoms (MUS). This systematic review describes the literature investigating the general effect of MBIs on MUS and identifies the effects of specific MBIs on specific MUS conditions. The preferred reporting items for systematic reviews and meta-analysis guidelines (PRISMA) and the modified Oxford quality scoring system (JADAD) were applied to the review, yielding an initial 1,556 articles. The search engines included PubMed, ScienceDirect, Web of Science, Scopus, EMBASE, and PsychINFO using the search terms: mindfulness, or mediations, or mindful or MBCT or MBSR and medically unexplained symptoms or MUS or fibromyalgia or FMS. A total of 24 articles were included in the final systematic review. MBIs showed large effects on socialization skills for chronic fatigue syndrome (d=0.65), anger in fibromyalgia (d=0.61), improvement of somatic symptoms (d=1.6) and sleep (d=1.12) for painful conditions, physical health for chronic back pain (d=0.51), and disease intensity for irritable bowel disease/syndrome (d=1.13). A manualized MBI that applies the four fundamental elements present in all types of interventions were critical to efficacy. These elements were psycho-education sessions specific to better understand the medical symptoms, the practice of awareness, the non-judgmental observance of the experience at the moment, and the compassion to ones’ self. The effectiveness of different mindfulness interventions necessitates giving attention to improve the gaps that were identified related to home-based practice monitoring, competency training of mindfulness teachers, and sound psychometric properties to measure the mindfulness practice.Keywords: mindfulness-based interventions, medically unexplained symptoms, mindfulness-based cognitive therapy, mindfulness-based stress reduction, fibromyalgia, irritable bowel syndrome
Procedia PDF Downloads 1442869 Seed Dressing and Foliar Spray of Green Bean (Phaseolus vulgaris L.) with Essential Oils and Disinfectants for Suppressing Root Rot and Wilt Incidence under Field Conditions
Authors: N. S. El-Mougy, M. M. Abdel-Kader, H. M. Abouelnasr
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The efficacy of two essential oils applied as a bean seed dressing followed by seedlings foliar spray with four commercial disinfectants against root rot and wilt incidence was evaluated under field conditions. The essential oils, grape seed and peppermint oils and the disinfectants, Gold, Revarest, Klenva, Malva were applied. Chitosan and the fungicide Topsin-M were used as comparison treatment. Essential oils individually or combined with disinfectants were applied as a bean seed dressing. Furthermore, emerged bean plants were sprayed with the same treatments. Under laboratory conditions, growth inhibition effect was observed for the isolated, tested fungi R. solani and F. oxysporum when exposed to essential oils individually or combined with disinfectants. A high inhibitor effect was recorded for peppermint followed by grape seed oils. Concentrations of 1% and 2% of chitosan as well as Topsin M at 400 ppm showed complete reduction (100%) in the two fungal growths. Under field conditions, the obtained results showed that the applied treatments of chitosan had a superior effect on root rot and wilt disease incidence compared with other tested treatments. It was found that seed coating treatment provides good protection of emerged green bean seeds against the root pathogens attack compared with the fungicide and control treatments. Also, the application of seed dressing with essential oils accompanied by seedling spray demonstrated similar results. It was observed that essential oils had an enhancing effect against disease incidence when combined with disinfectants compared with their application. The obvious yield increase was significantly higher in all applied treatments than in fungicide and control.Keywords: bean, disinfectants, essential oils, root rot, wilt
Procedia PDF Downloads 1652868 Study of Flow-Induced Noise Control Effects on Flat Plate through Biomimetic Mucus Injection
Authors: Chen Niu, Xuesong Zhang, Dejiang Shang, Yongwei Liu
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Fishes can secrete high molecular weight fluid on their body skin to enable their rapid movement in the water. In this work, we employ a hybrid method that combines Computational Fluid Dynamics (CFD) and Finite Element Method (FEM) to investigate the effects of different mucus viscosities and injection velocities on fluctuation pressure in the boundary layer and flow-induced structural vibration noise of a flat plate model. To accurately capture the transient flow distribution on the plate surface, we use Large Eddy Simulation (LES) while the mucus inlet is positioned at a sufficient distance from the model to ensure effective coverage. Mucus injection is modeled using the Volume of Fluid (VOF) method for multiphase flow calculations. The results demonstrate that mucus control of pulsating pressure effectively reduces flow-induced structural vibration noise, providing an approach for controlling flow-induced noise in underwater vehicles.Keywords: mucus, flow control, noise control, flow-induced noise
Procedia PDF Downloads 1512867 Organism Profile Causing Prosthetic Joint Infection Continues to Evolve
Authors: Bahaa Eldin Kornah
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The organism profile for peri-prosthetic joint infection caused by hematogenous seeding or direct inoculations is changing. The organisms that cause prosthetic joint infections range from normal skin colonizers to highly virulent pathogens. The pathogens continue to evolve. While Staphylococcus aureus continues to be the leading organism, gram-negative bacilli account for approximately 7% of cases and that incidence is increasing. Methicillin-resistant S. aureus(MRSA) accounts for approximately 10% of all infections occurring in the community setting and 20% of those in the health care setting. The list of organisms causing PJI has expanded in recent years. It is important to have an understanding of which organisms may be causing a periprosthetic joint infection based on where the patient contracted it and their recent medical history. Also, recent technology has expanded rapidly and new methods to detect the pathogen and why we failed in detecting it. There are a number of explanations for the latter finding, perhaps the most important reason being the liberal use of antibiotics that interferes with the isolation of the infective organism.Keywords: infection, periprosthetic, hip, organism profile, joint infection, joint infection
Procedia PDF Downloads 882866 The Type II Immune Response in Acute and Chronic Pancreatitis Mediated by STAT6 in Murine
Authors: Hager Elsheikh
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Context: Pancreatitis is a condition characterized by inflammation in the pancreas, which can lead to serious complications if untreated. Both acute and chronic pancreatitis are associated with immune reactions and fibrosis, which further damage the pancreas. The type 2 immune response, primarily driven by alternative activated macrophages (AAMs), plays a significant role in the development of fibrosis. The IL-4/STAT6 pathway is a crucial signaling pathway for the activation of M2 macrophages. Pancreatic fibrosis is induced by dysregulated inflammatory responses and can result in the autodigestion and necrosis of pancreatic acinar cells. Research Aim: The aim of this study is to investigate the impact of STAT6, a crucial molecule in the IL-4/STAT6 pathway, on the severity and development of fibrosis during acute and chronic pancreatitis. The research also aims to understand the influence of the JAK/STAT6 signaling pathway on the balance between fibrosis and regeneration in the presence of different macrophage populations. Methodology: The research utilizes murine models of acute and chronic pancreatitis induced by cerulean injection. Animal models will be employed to study the effect of STAT6 knockout on disease severity and fibrosis. Isolation of acinar cells and cell culture techniques will be used to assess the impact of different macrophage populations on wound healing and regeneration. Various techniques such as PCR, histology, immunofluorescence, and transcriptomics will be employed to analyze the tissues and cells. Findings: The research aims to provide insights into the mechanisms underlying tissue fibrosis and wound healing during acute and chronic pancreatitis. By investigating the influence of the JAK/STAT6 signaling pathway and different macrophage populations, the study aims to understand their impact on tissue fibrosis, disease severity, and pancreatic regeneration. Theoretical Importance: This research contributes to our understanding of the role of specific signaling pathways, macrophage polarization, and the type 2 immune response in pancreatitis. It provides insights into the molecular mechanisms underlying tissue fibrosis and the potential for targeted therapies. Data Collection and Analysis Procedures: Data will be collected through the use of murine models, isolation and culture of acinar cells, and various experimental techniques such as PCR, histology, immunofluorescence, and transcriptomics. Data will be analyzed using appropriate statistical methods and techniques, and the findings will be interpreted in the context of the research objectives. Conclusion: By investigating the mechanisms of tissue fibrosis and wound healing during acute and chronic pancreatitis, this research aims to enhance our understanding of the disease progression and potential therapeutic targets. The findings have theoretical importance in expanding our knowledge of pancreatic fibrosis and the role of macrophage polarization in the context of the type 2 immune response.Keywords: immunity in chronic diseases, pancreatitis, macrophages, immune response
Procedia PDF Downloads 412865 Genetic and Virulence Diversity among Alternaria carthami Isolates of India
Authors: Garima Anand, Rupam Kapoor
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Alternaria leaf spot caused by Alternaria carthami is one of the most devastating diseases of safflower. It has resulted in huge losses in crop production and cultivation leading to a fall out of India’s rank as the leading producer of safflower in the world. Understanding the diversity of any pathogen is essential for its management and for the development of disease control strategies. The diversity of A. carthami was therefore analysed on the basis of biochemical, pathogenicity and genetic lines using ISSR markers. Collections and isolations of 95 isolates of A. carthami were made from major safflower producing states of India. Virulence was analysed to evaluate the pathogenic potential of these isolates. The isolates from Bijapur, Dharwad districts (Karnataka), and Parbhani and Solapur districts (Maharashtra) were found to be highly virulent. The virulence assays showed low virulence levels (42%) for the largest part of the population. Biochemical characterization to assess aggressiveness of these isolates was done by estimating the activity of cell wall degrading enzymes where isolates from districts Dharwad, Bijapur of Karnataka and districts Parbhani and Latur of Maharashtra were found to be most aggressive. Genetic diversity among isolates of A. carthami was determined using eighteen ISSR markers. Distance analysis using neighbour joining method and PCoA analysis of the ISSR profiles divided the isolates into three sub-populations. The most virulent isolates clustered in one group in the dendrogram. The study provided no evidence for geographical clustering indicating that isolates are randomly spread across the states, signifying the high potential of the fungus to adapt to diverse regions. The study can, therefore, aid in the breeding and deployment of A. carthami resistant safflower varieties and in the management of Alternaria leaf spot disease.Keywords: alternaria leaf spot, genetic diversity, pathogenic potential, virulence
Procedia PDF Downloads 2572864 Targeting Matrix Metalloprotease-9 to Reduce Coronary Artery Manifestations of Kawasaki’s Disease
Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian
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Kawasaki disease (KD) is the primary cause of acquired pediatric heart disease as an acute vasculitis. In children with prolonged fever, rash, and inflammation of the mucosa KD must be considered as a clinical diagnosis. There is a persuasive suggestion of immune-mediated damage as the pathophysiologic cascade of KD. For example, the invasion of cytotoxic T-cells supports a viral etiology and the inflammasome of the innate immune system is a critical component in the vasculitis formation in KD. Animal models of KD propose the cytokine profiles, such as increased IL-1 and GM-CSF, which cause vascular damage. CRP and IFN-γ elevated expression and the upregulation of IL-6, and IL-10 production are also described in previous studies. Untreated KD is a critical risk factor for coronary artery diseases and myocardial infarction. Vascular damage may encompass amplified T-cell activity. SMAD3 is an essential molecule in down-regulating T-cells and increasing expression of FoxP3. It has a critical effect in the differentiation of regulatory T-cells. The discrepancy of regulatory T-cells and pro-inflammatory Th17 has been studied in acute coronary syndrome during KD. However in the coronary artery damaged lymphocytes and IgA plasma cells are seen at the lesion locations, the major immune cells in the coronary lesions are monocytes/macrophages and neutrophils. These cells secrete TNF-α, and activates matrix metalloprotease (MMP)-9, reducing the integrity of vessels and prompting patients to arise aneurysm. MMPs can break down the components of the extracellular matrix and assist immune cell movement. IVIG as an effective form of treatment clarified the role of the immune system, which may target pathogenic antigens and regulate cytokine production. Several reports have revealed that in the coronary arteries, high expression of MMP-9 in monocyte/macrophage results in pathologic cascades. Curcumin is a potent antioxidant and anti-inflammatory molecule. Curcumin decreases the production of reactive oxygen and nitrogen species and inhibits transcription factors like AP-1 and NF-κB. Curcumin also contains the characteristics of inhibitory effects on MMPs, especially MMP-9. The upregulation of MMP-9 is an important cellular response. Curcumin treatment caused a reverse effect and down-regulates MMP-9 gene expression which may fund the anti-inflammatory effect. Curcumin inhibits MMP-9 expression via PKC and AMPK-dependent pathways in Human monocytes cells. Elevated expression and activity of MMP-9 are correlated with advanced vascular lesions. AMPK controls lipid metabolism and oxidation, and protein synthesis. AMPK is also necessary for the MMP-9 activity and THP-1 cell adhesion to endothelial cells. Curcumin was shown to inhibit the activation of AMPKα. Compound C (AMPK inhibitor) inhibits MMP-9 expression level. Therefore, through inactivating AMPKs and PKC, curcumin decreases the MMP-9 level, which results in inhibiting monocyte/macrophage differentiation. Compound C also suppress the phosphorylation of three major classes of MAP kinase signaling, suggesting that curcumin may suppress MMP-9 level by inactivation of MAPK pathways. MAPK cascades are activated to induce the expression of MMP-9. Curcumin inhibits MAPKs phosphorylation, which contributes to the down-regulation of MMP-9. This study demonstrated that the potential inhibitory properties of curcumin over MMP-9 lead to a therapeutic strategy to reduce the risk of coronary artery involvement during KD.Keywords: MMP-9, coronary artery aneurysm, Kawasaki’s disease, curcumin, AMPK, immune system, NF-κB, MAPK
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