Search results for: acute hepatopancreatic necrosis disease
4120 DTI Connectome Changes in the Acute Phase of Aneurysmal Subarachnoid Hemorrhage Improve Outcome Classification
Authors: Sarah E. Nelson, Casey Weiner, Alexander Sigmon, Jun Hua, Haris I. Sair, Jose I. Suarez, Robert D. Stevens
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Graph-theoretical information from structural connectomes indicated significant connectivity changes and improved acute prognostication in a Random Forest (RF) model in aneurysmal subarachnoid hemorrhage (aSAH), which can lead to significant morbidity and mortality and has traditionally been fraught by poor methods to predict outcome. This study’s hypothesis was that structural connectivity changes occur in canonical brain networks of acute aSAH patients, and that these changes are associated with functional outcome at six months. In a prospective cohort of patients admitted to a single institution for management of acute aSAH, patients underwent diffusion tensor imaging (DTI) as part of a multimodal MRI scan. A weighted undirected structural connectome was created of each patient’s images using Constant Solid Angle (CSA) tractography, with 176 regions of interest (ROIs) defined by the Johns Hopkins Eve atlas. ROIs were sorted into four networks: Default Mode Network, Executive Control Network, Salience Network, and Whole Brain. The resulting nodes and edges were characterized using graph-theoretic features, including Node Strength (NS), Betweenness Centrality (BC), Network Degree (ND), and Connectedness (C). Clinical (including demographics and World Federation of Neurologic Surgeons scale) and graph features were used separately and in combination to train RF and Logistic Regression classifiers to predict two outcomes: dichotomized modified Rankin Score (mRS) at discharge and at six months after discharge (favorable outcome mRS 0-2, unfavorable outcome mRS 3-6). A total of 56 aSAH patients underwent DTI a median (IQR) of 7 (IQR=8.5) days after admission. The best performing model (RF) combining clinical and DTI graph features had a mean Area Under the Receiver Operator Characteristic Curve (AUROC) of 0.88 ± 0.00 and Area Under the Precision Recall Curve (AUPRC) of 0.95 ± 0.00 over 500 trials. The combined model performed better than the clinical model alone (AUROC 0.81 ± 0.01, AUPRC 0.91 ± 0.00). The highest-ranked graph features for prediction were NS, BC, and ND. These results indicate reorganization of the connectome early after aSAH. The performance of clinical prognostic models was increased significantly by the inclusion of DTI-derived graph connectivity metrics. This methodology could significantly improve prognostication of aSAH.Keywords: connectomics, diffusion tensor imaging, graph theory, machine learning, subarachnoid hemorrhage
Procedia PDF Downloads 1894119 Machine Learning for Disease Prediction Using Symptoms and X-Ray Images
Authors: Ravija Gunawardana, Banuka Athuraliya
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Machine learning has emerged as a powerful tool for disease diagnosis and prediction. The use of machine learning algorithms has the potential to improve the accuracy of disease prediction, thereby enabling medical professionals to provide more effective and personalized treatments. This study focuses on developing a machine-learning model for disease prediction using symptoms and X-ray images. The importance of this study lies in its potential to assist medical professionals in accurately diagnosing diseases, thereby improving patient outcomes. Respiratory diseases are a significant cause of morbidity and mortality worldwide, and chest X-rays are commonly used in the diagnosis of these diseases. However, accurately interpreting X-ray images requires significant expertise and can be time-consuming, making it difficult to diagnose respiratory diseases in a timely manner. By incorporating machine learning algorithms, we can significantly enhance disease prediction accuracy, ultimately leading to better patient care. The study utilized the Mask R-CNN algorithm, which is a state-of-the-art method for object detection and segmentation in images, to process chest X-ray images. The model was trained and tested on a large dataset of patient information, which included both symptom data and X-ray images. The performance of the model was evaluated using a range of metrics, including accuracy, precision, recall, and F1-score. The results showed that the model achieved an accuracy rate of over 90%, indicating that it was able to accurately detect and segment regions of interest in the X-ray images. In addition to X-ray images, the study also incorporated symptoms as input data for disease prediction. The study used three different classifiers, namely Random Forest, K-Nearest Neighbor and Support Vector Machine, to predict diseases based on symptoms. These classifiers were trained and tested using the same dataset of patient information as the X-ray model. The results showed promising accuracy rates for predicting diseases using symptoms, with the ensemble learning techniques significantly improving the accuracy of disease prediction. The study's findings indicate that the use of machine learning algorithms can significantly enhance disease prediction accuracy, ultimately leading to better patient care. The model developed in this study has the potential to assist medical professionals in diagnosing respiratory diseases more accurately and efficiently. However, it is important to note that the accuracy of the model can be affected by several factors, including the quality of the X-ray images, the size of the dataset used for training, and the complexity of the disease being diagnosed. In conclusion, the study demonstrated the potential of machine learning algorithms for disease prediction using symptoms and X-ray images. The use of these algorithms can improve the accuracy of disease diagnosis, ultimately leading to better patient care. Further research is needed to validate the model's accuracy and effectiveness in a clinical setting and to expand its application to other diseases.Keywords: K-nearest neighbor, mask R-CNN, random forest, support vector machine
Procedia PDF Downloads 1544118 Burden of Severe COVID-19 in Center of Iran: Results of Disability-Adjusted Life Years (DALYs)
Authors: Moslem Taheri Soodejani, Mohammad Hassan Lotfi
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Introduction: The outbreak of Covid-19 disease is an international public health concern. Therefore, the analysis of information related to mortality and disability due to COVID-19 is considered important, so the present study was designed and conducted with the aim of assessing COVID-19 Disability-Adjusted Life Years (DALYs) in Yazd. Methods: In Yazd province, all suspected cases of Covid-19 that would be referred to central hospitals in order to get confirmed through PCR or CT scan tests were recruited to our study. The fatality data of Covid- 19 was gathered from the forensic medicine organization. The Disability-Adjusted Life Years (DALYs) combines in one measure years of life lost (YLL), the loss of healthy life due to premature mortality and years of life lived with disability (YLD), the loss of healthy life because of disease and disability. Results: The total burden of COVID-19 was 23,472 years. The number of years lost due to premature death was 23385 and the number of years of life with disability due to COVID-19 was estimated to be 87 years. The disease burden was 12992 years for men and 10480 years for women. The overall incidence of COVID-19 was 1411 per 100,000, of which 1419 in men and 1402 in women per 100,000. Conclusion: The outbreak of the COVID-19 pandemic affected a large population and the residents of Yazd Province lost many years of their lives due to this disease.Keywords: DALY, covid- 19, Yazd, Iran
Procedia PDF Downloads 1914117 Twist2 Is a Key Regulator of Cell Proliferation in Acute Lymphoblastic Leukaemia
Authors: Magdalena Rusady Goey, Gordon Strathdee, Neil Perkins
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Background: Acute lymphoblastic leukaemia (ALL) is the most frequent type of childhood malignancy, accounting for 25% of all cases. TWIST2, a basic helix-loop-helix transcription factor, has been implicated in ALL development. Prior studies found that TWIST2 undergoes epigenetic silencing in more than 50% cases of ALL through promoter hypermethylation and suggested that re-expression of TWIST2 may inhibit cell growth/survival of leukaemia cell lines. TWIST2 has also been implicated as a regulator of NF-kappaB activity, which is constitutively active in leukaemia. Here, we use a lentiviral transductions system to confirm the importance of TWIST2 in controlling leukaemia cell growth and to investigate whether this is achieved through altered regulation of NF-kappaB activity. Method: Re-expression of TWIST2 in leukaemia cell lines was achieved using lentiviral-based transduction. The lentiviral vector also expresses enhanced green fluorescent protein (eGFP), allowing transduced cells to be tracked using flow cytometry. Analysis of apoptosis and cell proliferation were done using annexinV and VPD450 staining, respectively. Result and Discussion: TWIST2-expressing cells were rapidly depleted from a mixed population in ALL cell lines (NALM6 and Reh), indicating that TWIST2 inhibited cell growth/survival of ALL cells. In contrast, myeloid cell lines (HL60 and K562) were comparatively insensitive to TWIST2 re-expression. Analysis of apoptosis and cell proliferation found no significant induction of apoptosis, but did find a rapid induction of proliferation arrest in TWIST2-expressing Reh and NALM6 cells. Initial experiment with NF-kappaB inhibitor demonstrated that inhibition of NF-kappaB has similar impact on cell proliferation in the ALL cell lines, suggesting that TWITST2 may induce cell proliferation arrest through inhibition of NF-kappaB. Conclusion: The results of this study suggest that epigenetic inactivation of TWIST2 in primary ALL leads to increased proliferation, potentially by altering the regulation of NF-kappaB.Keywords: leukaemia, acute lymphoblastic leukaemia, NF-kappaB, TWIST2, lentivirus
Procedia PDF Downloads 3464116 In vitro Antiviral Activity of Ocimum sanctum against Animal Viruses
Authors: Anjana Goel, Ashok Kumar Bhatia
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Ocimum sanctum, a well known medicinal plant is used for various alignments in Ayurvedic medicines. It was found to be effective in treating the humans suffering from different viral infections like chicken pox, small pox, measles and influenza. In addition, curative effect of the plant in malignant patients was also reported. In the present study, leaves of this plant were screened against animal viruses i.e. Bovine Herpes Virus-type-1 (BHV-1), Foot and Mouth disease virus (FMDV) and Newcastle Disease Virus (NDV). BHV-1 and FMDV were screened in MDBK and BHK cell lines respectively using cytopathic inhibition test. While NDV was propagated in chick embryo fibroblast culture and tested by haemagglutination inhibition test. Maximum non toxic dose of aqueous extract of Ocimum sanctum leaves was calculated by MTT assay in all the cell cultures and nontoxic doses were used for antiviral activity against viruses. 98.4% and 85.3% protection were recorded against NDV and BHV-1 respectively. However, Ocimum sanctum extract failed to show any inhibitory effect on the cytopathic effect caused by FMD virus. It can be concluded that Ocimum sanctum is a very effective remedy for curing viral infections in animals also.Keywords: bovine herpes virus-type-1, foot and mouth disease virus, newcastle disease virus, Ocimum sanctum
Procedia PDF Downloads 2724115 Genomic Analysis of Whole Genome Sequencing of Leishmania Major
Authors: Fatimazahrae Elbakri, Azeddine Ibrahimi, Meryem Lemrani, Dris Belghyti
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Leishmaniasis represents a major public health problem because of the number of cases recorded each year and the wide distribution of the disease. It is a parasitic disease of flagellated protozoa transmitted by the bite of certain species of sandfly, causing a spectrum of clinical pathology in humans ranging from disfiguring skin lesions to fatal visceral leishmaniasis. Cutaneous leishmaniasis due to Leishmania major is a polymorphic disease; in fact, the infection can be asymptomatic, localized, or disseminated. The objective of this work is to determine the genomic diversity that contributes to clinical variability by trying to identify the variation in chromosome number and to extract SNPs and SNPs and InDels; it is based on four sequences (WGS) of Leishmania major available on NCBI in Fastq form, from three countries: Tunisia, Algeria, and Israel, the analysis is set up from a pipeline to facilitate the discovery of genetic diversity, in particular SNP and chromosomal somy.Keywords: Leshmania major, cutaneous Leishmania, NGS, genomic, somy, variant calling
Procedia PDF Downloads 794114 The X-Ray Response Team: Building a National Health Pre-Hospital Service
Authors: Julian Donovan, Jessica Brealey, Matthew Bowker, Marianne Feghali, Gregory Smith, Lee Thompson, Deborah Henderson
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This article details the development of the X-ray response team (XRT), a service that utilises innovative technology to safely deliver acute and elective imaging and medical assessment service in the pre-hospital and community setting. This involves a partnership between Northumbria Healthcare NHS Foundation Trust’s Radiology and Emergency Medicine departments and the North East Ambulance Service to create a multidisciplinary prehospital team. The team committed to the delivery of a two-day acute service every week, alongside elective referrals, starting in November 2020. The service was originally made available to a 15-mile radius surrounding the Northumbria Hospital. Due to demand, this was expanded to include the North Tyneside and Northumberland regions. The target population was specified as frail and vulnerable patients, as well as those deemed to benefit from staying in their own environment. Within the first two months, thirty-six percent of patients assessed were able to stay at home due to the provision of off-site imaging. In the future, this service aims to allow patient transfer directly to an appropriate ward or clinic, bypassing the emergency department to improve the patient journey and reduce emergency care pressures.Keywords: frailty, imaging, pre-hospital, X-ray
Procedia PDF Downloads 2014113 Quality of Life of Patients on Oral Antiplatelet Therapy in Outpatient Cardiac Department Dr. Hasan Sadikin Central General Hospital Bandung
Authors: Andhiani Sharfina Arnellya, Mochammad Indra Permana, Dika Pramita Destiani, Ellin Febrina
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Health Research Data, Ministry of Health of Indonesia in 2007, showed coronary heart disease (CHD) or coronary artery disease (CAD) was the third leading cause of death in Indonesia after hypertension and stroke with 7.2% incidence rate. Antiplatelet is one of the important therapy in management of patients with CHD. In addition to therapeutic effect on patients, quality of life is one aspect of another assessment to see the success of antiplatelet therapy. The purpose of this study was to determine the quality of life of patients on oral antiplatelet therapy in outpatient cardiac department Dr. Hasan Sadikin central general hospital, Bandung, Indonesia. This research is a cross sectional by collecting data through quality of life questionnaire of patients which performed prospectively as primary data and secondary data from medical record of patients. The results of this study showed that 54.3% of patients had a good quality of life, 45% had a moderate quality of life, and 0.7% had a poor quality of life. There are no significant differences in quality of life-based on age, gender, diagnosis, and duration of drug use.Keywords: antiplatelet, quality of life, coronary artery disease, coronary heart disease
Procedia PDF Downloads 3244112 Use of a Chagas Urine Nanoparticle Test (Chunap) to Correlate with Parasitemia Levels in T. cruzi/HIV Co-Infected Patients
Authors: Yagahira E. Castro-Sesquen, Robert H. Gilman, Carolina Mejia, Daniel E. Clark, Jeong Choi, Melissa J. Reimer-Mcatee, Rocio Castro, Jorge Flores, Edward Valencia-Ayala, Faustino Torrico, Ricardo Castillo-Neyra, Lance Liotta, Caryn Bern, Alessandra Luchini
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Early diagnosis of reactivation of Chagas disease in HIV patients could be lifesaving; however, in Latin American the diagnosis is performed by detection of parasitemia by microscopy which lacks sensitivity. To evaluate if levels of T. cruzi antigens in urine determined by Chunap (Chagas urine nanoparticle test) are correlated with parasitemia levels in T. cruzi/HIV co-infected patients. T. cruzi antigens in urine of HIV patients (N=55: 31 T. cruzi infected and 24 T. cruzi serology negative) were concentrated using hydrogel particles and quantified by Western Blot and a calibration curve. The percentage of Chagas positive patients determined by Chunap compared to blood microscopy, qPCR, and ELISA was 100% (6/6), 95% (18/19) and 74% (23/31), respectively. Chunap specificity was 91.7%. Linear regression analysis demonstrated a direct relationship between parasitemia levels (determined by qPCR) and urine T. cruzi antigen concentrations (p<0.001). A cut-off of > 105 pg was chosen to determine patients with reactivation of Chagas disease (6/6). Urine antigen concentration was significantly higher among patients with CD4+ lymphocyte counts below 200/mL (p=0.045). Chunap shows potential for early detection of reactivation and with appropriate adaptation can be used for monitoring Chagas disease status in T. cruzi/HIV co-infected patients.Keywords: antigenuria, Chagas disease, Chunap, nanoparticles, parasitemia, poly N-isopropylacrylamide (NIPAm)/trypan blue particles (polyNIPAm/TB), reactivation of Chagas disease.
Procedia PDF Downloads 3774111 A Field Study of Monochromatic Light Effects on Antibody Responses to Newcastle Disease by HI Test and the Correlation with ELISA
Authors: Seyed Mehrzad Pahlavani, Mozaffar Haji Jafari Anaraki, Sayma Mohammadi
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A total of 34700 day-old broilers were exposed to green, blue and yellow light using a light-emitting diode system for 6 weeks to investigate the effects of light wave length on antibody responses to Newcastle disease by HI test and the correlation with ELISA. 3 poultry house broiler farms with the same conditions was selected and the lightening system of each was set according to the requirement. Blood samples were taken from 20 chicks on days 1, 24 and 46 and the Newcastle virus specific antibody was titered in serum using HI an ELISA test. On day 24, the probability value of more than 0/05 was observed in HI and ELISA tests of all groups while at the end of breeding period, the average HI serum antibody titer was more in the green light than the yellow one while the blue light was not significantly different from both. At the last titration, the green light has got the highest titer of Newcastle antibodies. There were no significant differences of Newcastle antibody titers between all groups and ages in broiler pullets in ELISA. According to the sampling and analysis of HI and ELISA serum tests, there were no significant relationships between all broiler pullets breeding in green, blue and yellow light on days 24 and 46 and the P-value was more than 0/05. It is suggested that the monochromatic light is effective on broilers immunity against Newcastle disease.Keywords: monochromatic light, Newcastle disease, HI test, ELISA test
Procedia PDF Downloads 6574110 Intraoperative ICG-NIR Fluorescence Angiography Visualization of Intestinal Perfusion in Primary Pull-Through for Hirschsprung Disease
Authors: Mohammad Emran, Colton Wayne, Shannon M Koehler, P. Stephen Almond, Haroon Patel
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Purpose: Assessment of anastomotic perfusion in Hirschsprung disease using Indocyanine Green (ICG)-near-infrared (NIR) fluorescence angiography. Introduction: Anastomotic stricture and leak are well-known complications of Hirschsprung pull-through procedures. Complications are due to tension, infection, and/or poor perfusion. While a surgeon can visually determine and control the amount of tension and contamination, assessment of perfusion is subject to surgeon determination. Intraoperative use of ICG-NIR enhances this decision-making process by illustrating perfusion intensity and adequacy in the pulled-through bowel segment. This technique, proven to reduce anastomotic stricture and leak in adults, has not been studied in children to our knowledge. ICG, an FDA approved, nontoxic, non-immunogenic, intravascular (IV) dye, has been used in adults and children for over 60 years, with few side effects. ICG-NIR was used in this report to demonstrate the adequacy of perfusion during transanal pullthrough for Hirschsprung’s disease. Method: 8 patients with Hirschsprung disease were evaluated with ICG-NIR technology. Levels of affected area ranged from sigmoid to total colonic Hirschsprung disease. After leveling, but prior to anastomosis, ICG was administered at 1.25 mg (< 2 mg/kg) and perfusion visualized using an NIR camera, before and during anastomosis. Video and photo imaging was performed and perfusion of the bowel was compared to surrounding tissues. This showed the degree of perfusion and demarcation of perfused and non-perfused bowel. The anastomosis was completed uneventfully and the patients all did well. Results: There were no complications of stricture or leak. 5 of 8 patients (62.5%) had modification of the plan based on ICG-NIR imaging. Conclusion: Technologies that enhance surgeons’ ability to visualize bowel perfusion prior to anastomosis in Hirschsprung’s patients may help reduce post-operative complications. Further studies are needed to assess the potential benefits.Keywords: colonic anastomosis, fluorescence angiography, Hirschsprung disease, pediatric surgery, SPY
Procedia PDF Downloads 1414109 Gut-Microbiota-Brain-Axis, Leaky Gut, Leaky Brain: Pathophysiology of Second Brain Aging and Alzheimer’s Disease- A Neuroscientific Riddle
Authors: Bilal Ahmad
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Alzheimer’s disease (AD) is one of the most common neurodegenerative illnesses. However, how Gut-microbiota plays a role in the pathogenesis of AD is not well elucidated. The purpose of this literature review is to summarize and understand the current findings that may elucidate the gut microbiota's role in the development of AD. Methods: A literature review of all the relevant papers known to the author was conducted. Relevant articles, abstracts and research papers were collected from well-accepted web sources like PubMed, PMC, and Google Scholar. Results: Recent studies have shown that Gut-microbiota has an important role in the progression of AD via Gut-Microbiota-Brain Axis. The onset of AD supports the ‘Hygiene Hypothesis’, which shows that AD might begin in the Gut, causing dysbiosis, which interferes with the intestinal barrier by releasing pro-inflammatory cytokines and making its way up to the brain via the blood-brain barrier (BBB). Molecular mechanisms lipopolysaccharides and serotonin kynurenine (tryptophan) pathways have a direct association with inflammation, the immune system, neurodegeneration, and AD. Conclusion: The studies helped to analyze the molecular basis of AD, other neurological conditions like depression, autism, and Parkinson's disease and how they are linked to Gut-microbiota. Further, studies to explore the therapeutic effects of probiotics in AD and cognitive enhancement should be warranted to provide significant clinical and practical value.Keywords: gut-microbiota, Alzheimer’s disease, second brain aging, lipopolysaccharides, short-chain fatty acids
Procedia PDF Downloads 434108 Network Pharmacological Evaluation of Holy Basil Bioactive Phytochemicals for Identifying Novel Potential Inhibitors Against Neurodegenerative Disorder
Authors: Bhuvanesh Baniya
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Alzheimer disease is illnesses that are responsible for neuronal cell death and resulting in lifelong cognitive problems. Due to their unclear mechanism, there are no effective drugs available for the treatment. For a long time, herbal drugs have been used as a role model in the field of the drug discovery process. Holy basil in the Indian medicinal system (Ayurveda) is used for several neuronal disorders like insomnia and memory loss for decades. This study aims to identify active components of holy basil as potential inhibitors for the treatment of Alzheimer disease. To fulfill this objective, the Network pharmacology approach, gene ontology, pharmacokinetics analysis, molecular docking, and molecular dynamics simulation (MDS) studies were performed. A total of 7 active components in holy basil, 12 predicted neurodegenerative targets of holy basil, and 8063 Alzheimer-related targets were identified from different databases. The network analysis showed that the top ten targets APP, EGFR, MAPK1, ESR1, HSPA4, PRKCD, MAPK3, ABL1, JUN, and GSK3B were found as significant target related to Alzheimer disease. On the basis of gene ontology and topology analysis results, APP was found as a significant target related to Alzheimer’s disease pathways. Further, the molecular docking results to found that various compounds showed the best binding affinities. Further, MDS top results suggested could be used as potential inhibitors against APP protein and could be useful for the treatment of Alzheimer’s disease.Keywords: holy basil, network pharmacology, neurodegeneration, active phytochemicals, molecular docking and simulation
Procedia PDF Downloads 1014107 Molecular Detection of mRNA bcr-abl and Circulating Leukemic Stem Cells CD34+ in Patients with Acute Lymphoblastic Leukemia and Chronic Myeloid Leukemia and Its Association with Clinical Parameters
Authors: B. Gonzalez-Yebra, H. Barajas, P. Palomares, M. Hernandez, O. Torres, M. Ayala, A. L. González, G. Vazquez-Ortiz, M. L. Guzman
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Leukemia arises by molecular alterations of the normal hematopoietic stem cell (HSC) transforming it into a leukemic stem cell (LSC) with high cell proliferation, self-renewal, and cell differentiation. Chronic myeloid leukemia (CML) originates from an LSC-leading to elevated proliferation of myeloid cells and acute lymphoblastic leukemia (ALL) originates from an LSC development leading to elevated proliferation of lymphoid cells. In both cases, LSC can be identified by multicolor flow cytometry using several antibodies. However, to date, LSC levels in peripheral blood (PB) are not established well enough in ALL and CML patients. On the other hand, the detection of the minimal residue disease (MRD) in leukemia is mainly based on the identification of the mRNA bcr-abl gene in CML patients and some other genes in ALL patients. There is no a properly biomarker to detect MDR in both types of leukemia. The objective of this study was to determine mRNA bcr-abl and the percentage of LSC in peripheral blood of patients with CML and ALL and identify a possible association between the amount of LSC in PB and clinical data. We included in this study 19 patients with Leukemia. A PB sample was collected per patient and leukocytes were obtained by Ficoll gradient. The immunophenotype for LSC CD34+ was done by flow cytometry analysis with CD33, CD2, CD14, CD16, CD64, HLA-DR, CD13, CD15, CD19, CD10, CD20, CD34, CD38, CD71, CD90, CD117, CD123 monoclonal antibodies. In addition, to identify the presence of the mRNA bcr-abl by RT-PCR, the RNA was isolated using TRIZOL reagent. Molecular (presence of mRNA bcr-abl and LSC CD34+) and clinical results were analyzed with descriptive statistics and a multiple regression analysis was performed to determine statistically significant association. In total, 19 patients (8 patients with ALL and 11 patients with CML) were analyzed, 9 patients with de novo leukemia (ALL = 6 and CML = 3) and 10 under treatment (ALL = 5 and CML = 5). The overall frequency of mRNA bcr-abl was 31% (6/19), and it was negative in ALL patients and positive in 80% in CML patients. On the other hand, LSC was determined in 16/19 leukemia patients (%LSC= 0.02-17.3). The Novo patients had higher percentage of LSC (0.26 to 17.3%) than patients under treatment (0 to 5.93%). The amount of LSC was significantly associated with the amount of LSC were: absence of treatment, the absence of splenomegaly, and a lower number of leukocytes, negative association for the clinical variables age, sex, blasts, and mRNA bcr-abl. In conclusion, patients with de novo leukemia had a higher percentage of circulating LSC than patients under treatment, and it was associated with clinical parameters as lack of treatment, absence of splenomegaly and a lower number of leukocytes. The mRNA bcr-abl detection was only possible in the series of patients with CML, and molecular detection of LSC could be identified in the peripheral blood of all leukemia patients, we believe the identification of circulating LSC may be used as biomarker for the detection of the MRD in leukemia patients.Keywords: stem cells, leukemia, biomarkers, flow cytometry
Procedia PDF Downloads 3564106 Post COVID-19 Multi-System Inflammatory Syndrome Masquerading as an Acute Abdomen
Authors: Ali Baker, Russel Krawitz
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This paper describes a rare occurrence where a potentially fatal complication of COVID-19 infection (MIS-A) was misdiagnosed as an acute abdomen. As most patients with this syndrome present with fever and gastrointestinal symptoms, they may inadvertently fall under the care of the surgical unit. However, unusual imaging findings and a poor response to anti-microbial therapy should prompt clinicians to suspect a non-surgical etiology. More than half of MIS-A patients require ICU admission and vasopressor support. Prompt referral to a physician is key, as the cornerstone of treatment is IVIG and corticosteroid therapy. A 32 year old woman presented with right sided abdominal pain and fevers. She had also contracted COVID-19 two months earlier. Abdominal examination revealed generalised right sided tenderness. The patient had raised inflammatory markers, but other blood tests were unremarkable. CT scan revealed extensive lymphadenopathy along the ileocolic chain. The patient proved to be a diagnostic dilemma. She was reviewed by several surgical consultants and discussed with several inpatient teams. Although IV antibiotics were commenced, the right sided abdominal pain, and fevers persisted. Pan-culture returned negative. A mild cholestatic derangement developed. On day 5, the patient underwent preparation for colonoscopy to assess for a potential intraluminal etiology. The following day, the patient developed sinus tachycardia and hypotension that was refractory to fluid resuscitation. That patient was transferred to ICU and required vasopressor support. Repeat CT showed peri-portal edema and a thickened gallbladder wall. On re-examination, the patient was Murphy’s sign positive. Biliary ultrasound was equivocal for cholecystitis. The patient was planned for diagnostic laparoscopy. The following morning, a marked rise in cardiac troponin was discovered, and a follow-up echocardiogram revealed moderate to severe global systolic dysfunction. The impression was post-COVID MIS with myocardial involvement. IVIG and Methylprednisolone infusions were commenced. The patient had a great response. Vasopressor support was weaned, and the patient was discharged from ICU. The patient continued to improve clinically with oral prednisolone, and was discharged on day 17. Although MIS following COVID-19 infection is well-described syndrome in children, only recently has it come to light that it can occur in adults. The exact incidence is unknown, but it is thought to be rare. A recent systematic review found only 221 cases of MIS-A, which could be included for analysis. Symptoms vary, but the most frequent include fever, gastrointestinal, and mucocutaneous. Many patients progress to multi-organ failure and require vasopressor support. 7% succumb to the illness. The pathophysiology of MIS is only partly understood. It shares similarities with Kawasaki disease, macrophage activation syndrome, and cytokine release syndrome. Importantly, by definition, the patient must have an absence of severe respiratory symptoms. It is thought to be due to a dysregulated immune response to the virus. Potential mechanisms include reduced levels of neutralising antibodies and autoreactive antibodies that promote inflammation. Further research into MIS-A is needed. Although rare, this potentially fatal syndrome should be considered in the unwell surgical patient who has recently contracted COVID-19 and poses a diagnostic dilemma.Keywords: acute-abdomen, MIS, COVID-19, ICU
Procedia PDF Downloads 1234105 Temporal Profile of T2 MRI and 1H-MRS in the MDX Mouse Model of Duchenne Muscular Dystrophy
Authors: P. J. Sweeney, T. Ahtoniemi, J. Puoliväli, T. Laitinen, K.Lehtimäki, A. Nurmi, D. Wells
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Duchenne muscular dystrophy (DMD) is an X-linked, lethal muscle wasting disease for which there are currently no treatment that effectively prevents the muscle necrosis and progressive muscle loss. DMD is among the most common of inherited diseases affecting around 1/3500 live male births. MDX (X-linked muscular dystrophy) mice only partially encapsulate the disease in humans and display weakness in muscles, muscle damage and edema during a period deemed the “critical period” when these mice go through cycles of muscular degeneration and regeneration. Although the MDX mutant mouse model has been extensively studied as a model for DMD, to-date an extensive temporal, non-invasive imaging profile that utilizes magnetic resonance imaging (MRI) and 1H-magnetic resonance spectroscopy (1H-MRS) has not been performed.. In addition, longitudinal imaging characterization has not coincided with attempts to exacerbate the progressive muscle damage by exercise. In this study we employed an 11.7 T small animal MRI in order to characterize the MRI and MRS profile of MDX mice longitudinally during a 12 month period during which MDX mice were subjected to exercise. Male mutant MDX mice (n=15) and male wild-type mice (n=15) were subjected to a chronic exercise regime of treadmill walking (30 min/ session) bi-weekly over the whole 12 month follow-up period. Mouse gastrocnemius and tibialis anterior muscles were profiled with baseline T2-MRI and 1H-MRS at 6 weeks of age. Imaging and spectroscopy was repeated again at 3 months, 6 months, 9 months and 12 months of age. Plasma creatine kinase (CK) level measurements were coincided with time-points for T2-MRI and 1H-MRS, but also after the “critical period” at 10 weeks of age. The results obtained from this study indicate that chronic exercise extends dystrophic phenotype of MDX mice as evidenced by T2-MRI and1H-MRS. T2-MRI revealed extent and location of the muscle damage in gastrocnemius and tibialis anterior muscles as hyperintensities (lesions and edema) in exercised MDX mice over follow-up period.. The magnitude of the muscle damage remained stable over time in exercised mice. No evident fat infiltration or cumulation to the muscle tissues was seen at any time-point in exercised MDX mice. Creatine, choline and taurine levels evaluated by 1H-MRS from the same muscles were found significantly decreased in each time-point, Extramyocellular (EMCL) and intramyocellular lipids (IMCL) did not change in exercised mice supporting the findings from anatomical T2-MRI scans for fat content. Creatine kinase levels were found to be significantly higher in exercised MDX mice during the follow-up period and importantly CK levels remained stable over the whole follow-up period. Taken together, we have described here longitudinal prophile for muscle damage and muscle metabolic changes in MDX mice subjected to chronic exercised. The extent of the muscle damage by T2-MRI was found to be stable through the follow-up period in muscles examined. In addition, metabolic profile, especially creatine, choline and taurine levels in muscles, was found to be sustained between time-points. The anatomical muscle damage evaluated by T2-MRI was supported by plasma CK levels which remained stable over the follow-up period. These findings show that non-invasive imaging and spectroscopy can be used effectively to evaluate chronic muscle pathology. These techniques can be also used to evaluate the effect of various manipulations, like here exercise, on the phenotype of the mice. Many of the findings we present here are translatable to clinical disease, such as decreased creatine, choline and taurine levels in muscles. Imaging by T2-MRI and 1H-MRS also revealed that fat content or extramyocellar and intramyocellular lipids, respectively, are not changed in MDX mice, which is in contrast to clinical manifestation of the Duchenne’s muscle dystrophy. Findings show that non-invasive imaging can be used to characterize the phenotype of a MDX model and its translatability to clinical disease, and to study events that have traditionally been not examined, like here rigorous exercise related sustained muscle damage after the “critical period”. The ability for this model to display sustained damage beyond the spontaneous “critical period“ and in turn to study drug effects on this extended phenotype will increase the value of the MDX mouse model as a tool to study therapies and treatments aimed at DMD and associated diseases.Keywords: 1H-MRS, MRI, muscular dystrophy, mouse model
Procedia PDF Downloads 3574104 Analysis and Rule Extraction of Coronary Artery Disease Data Using Data Mining
Authors: Rezaei Hachesu Peyman, Oliyaee Azadeh, Salahzadeh Zahra, Alizadeh Somayyeh, Safaei Naser
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Coronary Artery Disease (CAD) is one major cause of disability in adults and one main cause of death in developed. In this study, data mining techniques including Decision Trees, Artificial neural networks (ANNs), and Support Vector Machine (SVM) analyze CAD data. Data of 4948 patients who had suffered from heart diseases were included in the analysis. CAD is the target variable, and 24 inputs or predictor variables are used for the classification. The performance of these techniques is compared in terms of sensitivity, specificity, and accuracy. The most significant factor influencing CAD is chest pain. Elderly males (age > 53) have a high probability to be diagnosed with CAD. SVM algorithm is the most useful way for evaluation and prediction of CAD patients as compared to non-CAD ones. Application of data mining techniques in analyzing coronary artery diseases is a good method for investigating the existing relationships between variables.Keywords: classification, coronary artery disease, data-mining, knowledge discovery, extract
Procedia PDF Downloads 6574103 Long-Term Results of Surgical Treatment of Atrial Fibrillation in Patients with Coronary Heart Disease: One Center Experience
Authors: Emil Sakharov, Alex Zotov, Ilkin Osmanov, Oleg Shelest, Aleksander Troitskiy, Robert Khabazov
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Objective: Since 2015, our center has been actively implementing methods of surgical correction of atrial fibrillation, in particular, in patients with coronary heart disease. The study presents a comparative analysis of the late postoperative period in patients with coronary artery bypass grafting and atrial fibrillation. Methods: The study included 150 patients with ischemic heart disease and atrial fibrillation for the period from 2015 to 2021. Patients were divided into 2 groups. The first group is represented by patients with ischemic heart disease and atrial fibrillation who underwent coronary bypass surgery and surgical correction of atrial fibrillation (N=50). The second group is represented by patients with ischemic heart disease and atrial fibrillation who underwent only myocardial revascularization (N=100). Patients were comparable in age, gender, and initial severity of the condition. Among the patients in group 1 there were 82% were men, while in the second group, their number was 75%. Among the patients of the first group, there were 36% with persistent atrial fibrillation, 20% with long-term persistent atrial fibrillation. In the second group, 10% with persistent atrial fibrillation and 17% with long-term persistent atrial fibrillation. Results: Average follow-up for groups 1 and 2 amounted to 47 months. There were no complications in group 1, such as bleeding and stroke. There was only 1 patient in group 1, who had died from cardiovascular disease. Freedom of atrial fibrillation was in 82% without AADs therapy. In group 2 there were 8 patients who had died from cardiovascular diseases and total freedom of atrial fibrillation was in 35% of patients, among which 42.8% had additional AADs therapy. Follow-up data are presented in Table 2. Progression of heart failure was observed in 3% in group 1 and 7% in group 2. Combined endpoints (recurrence of AF, stroke, progression of heart failure, myocardial infarction) were achieved in 16% in group 1 and 34% in group 2, respectively. Freedom from atrial fibrillation without antiarrhythmic therapy was 82% for group 1 and 35% for group 2. In the first group, there is a more pronounced decrease in heart failure rates. Deaths from cardiovascular causes were recorded in 2% for group 1 and 7% for group 2. Conclusion: Surgical treatment of atrial fibrillation helps to reduce adverse complications in the late postoperative period and contributes to the regression of heart failure.Keywords: atrial fibrillation, coronary artery bypass grafting, ischaemic heart disease, heart failure
Procedia PDF Downloads 1194102 An Exploration of the Pancreatic Cancer miRNome during the Progression of the Disease
Authors: Barsha Saha, Shouvik Chakravarty, Sukanta Ray, Kshaunish Das, Nidhan K. Biswas, Srikanta Goswami
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Pancreatic Ductal Adenocarcinoma is a well-recognised cause of cancer death with a five-year survival rate of about 9%, and its incidence in India has been found to be increased manifold in recent years. Due to delayed detection, this highly metastatic disease has a poor prognosis. Several molecular alterations happen during the progression of the disease from pre-cancerous conditions, and many such alterations could be investigated for their biomarker potential. MicroRNAs have been shown to be prognostic for PDAC patients in a variety of studies. We hereby used NGS technologies to evaluate the role of small RNA changes during pancreatic cancer development from chronic pancreatitis. Plasma samples were collected from pancreatic cancer patients (n=16), chronic pancreatitis patients (n=8), and also from normal individuals (n=16). Pancreatic tumour tissue (n=5) and adjacent normal tissue samples (n=5) were also collected. Sequencing of small RNAs was carried out after small RNAs were isolated from plasma samples and tissue samples. We find that certain microRNAs are highly deregulated in pancreatic cancer patients in comparison to normal samples. A combinatorial analysis of plasma and tissue microRNAs and subsequent exploration of their targets and altered molecular pathways could not only identify potential biomarkers for disease diagnosis but also help to understand the underlying mechanism.Keywords: small RNA sequencing, pancreatic cancer, biomarkers, tissue sample
Procedia PDF Downloads 944101 John Cunningham Virus Interaction with Multiple Sclerosis Disease Progression
Authors: Sina Mahdavi
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Background and Objective: Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the central nervous system (CNS) that affects the myelination process in the CNS. Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially the John Cunningham virus (JCV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on JCV infection in MS disease progression. Materials and Methods: For this study, the keywords "Multiple sclerosis", " John Cunningham virus ", and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2019 and 2022 were searched, and 12 articles were chosen, studied, and analyzed. Results: MS patients are candidates for natalizumab therapy, which inhibits lymphocyte migration and increases the risk of progressive multifocal leukoencephalopathy (PML), a rare lytic infection of glial cells caused by JCV. Oligodendrocytes may be the target of JCV infection in the central nervous system (CNS). Conclusion: There is a high expression of JCV during the natalizumab treatment period for MS patients, suggesting that the virus may play a role in the development of MS by inducing an inflammatory state. Therefore, it is necessary to evaluate anti-JCV antibody serum as an important risk factor for the development of PML before deciding on the treatment course for these patients.Keywords: multiple sclerosis, John Cunningham virus, central nervous system, autoimmunity
Procedia PDF Downloads 1364100 Multi-Layer Perceptron and Radial Basis Function Neural Network Models for Classification of Diabetic Retinopathy Disease Using Video-Oculography Signals
Authors: Ceren Kaya, Okan Erkaymaz, Orhan Ayar, Mahmut Özer
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Diabetes Mellitus (Diabetes) is a disease based on insulin hormone disorders and causes high blood glucose. Clinical findings determine that diabetes can be diagnosed by electrophysiological signals obtained from the vital organs. 'Diabetic Retinopathy' is one of the most common eye diseases resulting on diabetes and it is the leading cause of vision loss due to structural alteration of the retinal layer vessels. In this study, features of horizontal and vertical Video-Oculography (VOG) signals have been used to classify non-proliferative and proliferative diabetic retinopathy disease. Twenty-five features are acquired by using discrete wavelet transform with VOG signals which are taken from 21 subjects. Two models, based on multi-layer perceptron and radial basis function, are recommended in the diagnosis of Diabetic Retinopathy. The proposed models also can detect level of the disease. We show comparative classification performance of the proposed models. Our results show that proposed the RBF model (100%) results in better classification performance than the MLP model (94%).Keywords: diabetic retinopathy, discrete wavelet transform, multi-layer perceptron, radial basis function, video-oculography (VOG)
Procedia PDF Downloads 2594099 Development of Chronic Obstructive Pulmonary Disease (COPD) Proforma (E-ICP) to Improve Guideline Adherence in Emergency Department: Modified Delphi Study
Authors: Hancy Issac, Gerben Keijzers, Ian Yang, Clint Moloney, Jackie Lea, Melissa Taylor
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Introduction: Chronic obstructive pulmonary disease guideline non-adherence is associated with a reduction in health-related quality of life in patients (HRQoL). Improving guideline adherence has the potential to mitigate fragmented care thereby sustaining pulmonary function, preventing acute exacerbations, reducing economic health burdens, and enhancing HRQoL. The development of an electronic proforma stemming from expert consensus, including digital guideline resources and direct interdisciplinary referrals is hypothesised to improve guideline adherence and patient outcomes for emergency department (ED) patients with COPD. Aim: The aim of this study was to develop consensus among ED and respiratory staff for the correct composition of a COPD electronic proforma that aids in guideline adherence and management in the ED. Methods: This study adopted a mixed-method design to develop the most important indicators of care in the ED. The study involved three phases: (1) a systematic literature review and qualitative interdisciplinary staff interviews to assess barriers and solutions for guideline adherence and qualitative interdisciplinary staff interviews, (2) a modified Delphi panel to select interventions for the proforma, and (3) a consensus process through three rounds of scoring through a quantitative survey (ED and Respiratory consensus) and qualitative thematic analysis on each indicator. Results: The electronic proforma achieved acceptable and good internal consistency through all iterations from national emergency department and respiratory department interdisciplinary experts. Cronbach’s alpha score for internal consistency (α) in iteration 1 emergency department cohort (EDC) (α = 0.80 [CI = 0.89%]), respiratory department cohort (RDC) (α = 0.95 [CI = 0.98%]). Iteration 2 reported EDC (α = 0.85 [CI = 0.97%]) and RDC (α = 0.86 [CI = 0.97%]). Iteration 3 revealed EDC (α = 0.73 [CI = 0.91%]) and RDC (α = 0.86 [CI = 0.95%]), respectively. Conclusion: Electronic proformas have the potential to facilitate direct referrals from the ED leading to reduced hospital admissions, reduced length of hospital stays, holistic care, improved health care and quality of life and improved interdisciplinary guideline adherence.Keywords: COPD, electronic proforma, modified delphi study, interdisciplinary, guideline adherence, COPD-X plan
Procedia PDF Downloads 604098 New Quinazoline Derivative Exhibit Cytotoxic Effect agaisnt MCF-7 Human Breast Cancer Cell
Authors: Maryam Zahedifard, Fadhil Lafta Faraj, Nazia Abdul Majid, Hapipah Mohd Ali, Mahmood Ameen Abdulla
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The new quinazoline Schiff bases have been synthesized through condensation reaction of 2-aminobenzhydrazide with 5-bromosalicylaldehyde and 3-methoxy-5-bromosalicylaldehyde. The compound was investigated for anticancer activity against MCF-7 human breast cancer cell line. It demonstrated a remarkable antiproliferative effect, with an IC50 value of 3.41±0.34, after 72 hours of treatment. Most apoptosis morphological features in treated MCF-7 cells were observed by AO/PI staining. The results of cell cycle analysis indicate that compounds did not induce S and M phase arrest in cell after 24 hours of treatment. Furthermore, MCF-7 cells treated with compound subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome C release as well as increase in ROS generation. We also found activation of caspases 3/7 and -9. Moreover, acute toxicity results demonstrated the nontoxic nature of the compounds in mice. Our results showed the selected compound significantly induce apoptosis in MCF-7 cells via intrinsic pathway, which might be considered as a potential candidate for further in vivo and clinical breast cancer studies.Keywords: quinazoline Schiff base, apoptosis, MCF-7, caspase, cell cycle, acute toxicity
Procedia PDF Downloads 4424097 MR Imaging Spectrum of Intracranial Infections: An Experience of 100 Cases in a Tertiary Hospital in Northern India
Authors: Avik Banerjee, Kavita Saggar
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Infections of the nervous system and adjacent structures are often life-threatening conditions. Despite the recent advances in neuroimaging evaluation, the diagnosis of unclear infectious CNS disease remains a challenge. Our aim is to evaluate the typical and atypical neuro-imaging features of the various routinely encountered CNS infected patients so as to form guidelines for their imaging recognition and differentiation from tumoral, vascular and other entities that warrant a different line of therapy.Keywords: central nervous system (CNS), Cerebro Spinal Fluid (Csf), Creutzfeldt Jakob Disease (CJD), progressive multifocal leukoencephalopathy (PML)
Procedia PDF Downloads 3014096 The GRIT Study: Getting Global Rare Disease Insights Through Technology Study
Authors: Aneal Khan, Elleine Allapitan, Desmond Koo, Katherine-Ann Piedalue, Shaneel Pathak, Utkarsh Subnis
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Background: Disease management of metabolic, genetic disorders is long-term and can be cumbersome to patients and caregivers. Patient-Reported Outcome Measures (PROMs) have been a useful tool in capturing patient perspectives to help enhance treatment compliance and engagement with health care providers, reduce utilization of emergency services, and increase satisfaction with their treatment choices. Currently, however, PROMs are collected during infrequent and decontextualized clinic visits, which makes translation of patient experiences challenging over time. The GRIT study aims to evaluate a digital health journal application called Zamplo that provides a personalized health diary to record self-reported health outcomes accurately and efficiently in patients with metabolic, genetic disorders. Methods: This is a randomized controlled trial (RCT) (1:1) that assesses the efficacy of Zamplo to increase patient activation (primary outcome), improve healthcare satisfaction and confidence to manage medications (secondary outcomes), and reduce costs to the healthcare system (exploratory). Using standardized online surveys, assessments will be collected at baseline, 1 month, 3 months, 6 months, and 12 months. Outcomes will be compared between patients who were given access to the application versus those with no access. Results: Seventy-seven patients were recruited as of November 30, 2021. Recruitment for the study commenced in November 2020 with a target of n=150 patients. The accrual rate was 50% from those eligible and invited for the study, with the majority of patients having Fabry disease (n=48) and the remaining having Pompe disease and mitochondrial disease. Real-time clinical responses, such as pain, are being measured and correlated to disease-modifying therapies, supportive treatments like pain medications, and lifestyle interventions. Engagement with the application, along with compliance metrics of surveys and journal entries, are being analyzed. An interim analysis of the engagement data along with preliminary findings from this pilot RCT, and qualitative patient feedback will be presented. Conclusions: The digital self-care journal provides a unique approach to disease management, allowing patients direct access to their progress and actively participating in their care. Findings from the study can help serve the virtual care needs of patients with metabolic, genetic disorders in North America and the world over.Keywords: eHealth, mobile health, rare disease, patient outcomes, quality of life (QoL), pain, Fabry disease, Pompe disease
Procedia PDF Downloads 1514095 Endothelial Dysfunction in Non-Alcoholic Fatty Liver Disease: An Updated Meta-Analysis
Authors: Anit S. Malhotra, Ajay Duseja, Neelam Chadha
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Endothelial dysfunction is a precursor to atherosclerosis, and flow-mediated dilatation (FMD) in the brachial artery is the commonest method to evaluate endothelial function in humans. Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver disorders encountered in clinical practice. An earlier meta-analysis had quantitatively assessed the degree of endothelial dysfunction using FMD. However, the largest study investigating the relation of FMD with NAFLD was published after that meta-analysis. In addition, that meta-analysis did not include some studies, including one from our centre. Therefore, an updating the previous meta-analysis was considered important. We searched PubMed, Cochrane Library, Embase, Scopus, SCI, Google Scholar, conference proceedings, and references of included studies till June 2017 to identify observational studies evaluating endothelial function using FMD in patients with non-alcoholic fatty liver disease. Data was analyzed using MedCalc. Fourteen studies were found eligible for inclusion in the meta-analysis. Patients with NAFLD had lower brachial artery FMD as compared to controls, standardized mean difference (random effects model) being –1.279%; 95% confidence interval (CI), –1.478 to –0.914. The effect size became smaller after addition of the recent study with the largest sample size was included compared with the earlier meta-analysis. In conclusion, patients with NAFLD had low FMD values indicating that they are at a higher risk of cardiovascular disease although our results suggest the effect size is not as large as reported previously.Keywords: endothelial dysfunction, flow-mediated dilatation, meta-analysis, non-alcoholic fatty liver disease
Procedia PDF Downloads 1904094 Brain Atrophy in Alzheimer's Patients
Authors: Tansa Nisan Gunerhan
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Dementia comes in different forms, including Alzheimer's disease. The most common dementia diagnosis among elderly individuals is Alzheimer's disease. On average, for patients with Alzheimer’s, life expectancy is around 4-8 years after the diagnosis; however, expectancy can go as high as twenty years or more, depending on the shrinkage of the brain. Normally, along with aging, the brain shrinks at some level but doesn’t lose a vast amount of neurons. However, Alzheimer's patients' neurons are destroyed rapidly; hence problems with loss of memory, communication, and other metabolic activities begin. The toxic changes in the brain affect the stability of the neurons. Beta-amyloid and tau are two proteins that are believed to play a role in the development of Alzheimer's disease through their toxic changes. Beta-amyloid is a protein that is produced in the brain and is normally broken down and removed from the body. However, in people with Alzheimer's disease, the production of beta-amyloid increases, and it begins to accumulate in the brain. These plaques are thought to disrupt communication between nerve cells and may contribute to the death of brain cells. Tau is a protein that helps to stabilize microtubules, which are essential for the transportation of nutrients and other substances within brain cells. In people with Alzheimer's disease, tau becomes abnormal and begins to accumulate inside brain cells, forming neurofibrillary tangles. These tangles disrupt the normal functioning of brain cells and may contribute to their death, forming amyloid plaques which are deposits of a protein called amyloid-beta that build up between nerve cells in the brain. The accumulation of amyloid plaques and neurofibrillary tangles in the brain is thought to contribute to the shrinkage of brain tissue. As the brain shrinks, the size of the brain may decrease, leading to a reduction in brain volume. Brain atrophy in Alzheimer's disease is often accompanied by changes in the structure and function of brain cells and the connections between them, leading to a decline in brain function. These toxic changes that accumulate can cause symptoms such as memory loss, difficulty with thinking and problem-solving, and changes in behavior and personality.Keywords: Alzheimer, amyloid-beta, brain atrophy, neuron, shrinkage
Procedia PDF Downloads 954093 4(3H)-Quinazolinone Derivatives' Synthesis and Evaluation as Antimalarial and Anti-Leishmanial Agents
Authors: Alemu Tadesse Feroche
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In this study, some 2, 3 distributed quinazoline -4 (3H) - one derivative were synthesized using a three-step synthetic route. They were obtained in a good yield (59.5-85%) by applying different chemical reactions like cyclization and condensation reactions. The chemical structure of the final compounds was also verified by spectroscopic methods (IR, ¹HNMR) and elemental microanalysis. The in vivo antimalarial activity of these compounds on P. berghei infected mice was found to be moderate to high at an oral dose of 0.04846 mmol/kg /day. This is equal to 25 mg/kg of chloroquine phosphate, which causes 100% inhibition of the parasite. It is worth mentioning that most active compounds (E) -3 Phenyl -2- [2- (pyridine -4- yl) vinyl] -4 (3H) -quinazolinone IVa (64.02%, (E)-2-[2-(4 - Hydroxy-3 - methoxystyryl) - vinyl) -3 - phenyl -4 (3H ) - quinazolinone IVc (77.25%) and (E)-2 –[2 –(Pyridin -4-yl) –vinyl] -3 phenenylamine -4(3H) quinazolinone IVe (73.54%) showed a dose-dependent increase in present suppression in antimalarial activities. Furthermore, the synthesized compounds were screened for their in vitro antileishmanial activity against L. aethiopica isolate (CL/039/09). All tested compounds (IVa (0.03766 ug/ml), IVb (0.00538 ug/ml, IVc (0.00412 ug/ml, IVd (0.00110 ug/ml), IVe (0.03017 ug/ml) and IVf (0.03894 ug/ml)) showed excellent potency that is much better than amphotericin B (IC50 = 0,04359 ug/ml). The results of acute toxicity indicated that all test compounds (IVa –IVf) proved to be nontoxic and well tolerated by the experimental animals up to 300 mg/kg in oral and 140 mg/kg in parental studies.Keywords: 4(3H)-quinazolinone, in vivo antimalarial activity, in vitro antileishmanial activity, acute toxicity
Procedia PDF Downloads 1004092 Cost-Effective and Optimal Control Analysis for Mitigation Strategy to Chocolate Spot Disease of Faba Bean
Authors: Haileyesus Tessema Alemneh, Abiyu Enyew Molla, Oluwole Daniel Makinde
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Introduction: Faba bean is one of the most important grown plants worldwide for humans and animals. Several biotic and abiotic elements have limited the output of faba beans, irrespective of their diverse significance. Many faba bean pathogens have been reported so far, of which the most important yield-limiting disease is chocolate spot disease (Botrytis fabae). The dynamics of disease transmission and decision-making processes for intervention programs for disease control are now better understood through the use of mathematical modeling. Currently, a lot of mathematical modeling researchers are interested in plant disease modeling. Objective: In this paper, a deterministic mathematical model for chocolate spot disease (CSD) on faba bean plant with an optimal control model was developed and analyzed to examine the best strategy for controlling CSD. Methodology: Three control interventions, quarantine (u2), chemical control (u3), and prevention (u1), are employed that would establish the optimal control model. The optimality system, characterization of controls, the adjoint variables, and the Hamiltonian are all generated employing Pontryagin’s maximum principle. A cost-effective approach is chosen from a set of possible integrated strategies using the incremental cost-effectiveness ratio (ICER). The forward-backward sweep iterative approach is used to run numerical simulations. Results: The Hamiltonian, the optimality system, the characterization of the controls, and the adjoint variables were established. The numerical results demonstrate that each integrated strategy can reduce the diseases within the specified period. However, due to limited resources, an integrated strategy of prevention and uprooting was found to be the best cost-effective strategy to combat CSD. Conclusion: Therefore, attention should be given to the integrated cost-effective and environmentally eco-friendly strategy by stakeholders and policymakers to control CSD and disseminate the integrated intervention to the farmers in order to fight the spread of CSD in the Faba bean population and produce the expected yield from the field.Keywords: CSD, optimal control theory, Pontryagin’s maximum principle, numerical simulation, cost-effectiveness analysis
Procedia PDF Downloads 874091 Changing Left Ventricular Hypertrophy After Kidney Transplantation
Authors: Zohreh Rostami, Arezoo Khosravi, Mohammad Nikpoor Aghdam, Mahmood Salesi
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Background: Cardiovascular mortality in chronic kidney disease (CKD) and end stage renal disease (ESRD) patients have a strong relationship with baseline or progressive left ventricular hypertrophy (LVH) meanwhile in hemodialysis patients 10% decrement in left ventricular mass was associated with 28% reduction in cardiovascular mortality risk. In consonance with these arguments, we designed a study to measure morphological and functional echocardiographic variations early after transplantation. Method: The patients with normal renal function underwent two advanced echocardiographic studies to examine the structural and functional changes in left ventricular mass before and 3-month after transplantation. Results: From a total of 23 participants 21(91.3%) presented with left ventricular hypertrophy, 60.9% in eccentric and 30.4% in concentric group. Diastolic dysfunction improved in concentric group after transplantation. Both in pre and post transplantation global longitudinal strain (GLS)- average in eccentric group was more than concentric (-17.45 ± 2.75 vs -14.3 ± 3.38 p=0.03) and (-18.08 ± 2.6 vs -16.1 ± 2.7 p= 0.04) respectively. Conclusion: Improvement and recovery of left ventricular function in concentric group was better and sooner than eccentric after kidney transplantation. Although fractional shortening and diastolic function and GLS-4C in pre-transplantation in concentric group was worse than eccentric, but therapeutic response to kidney transplantation in concentric was more and earlier than eccentric group.Keywords: chronic kidney disease, end stage renal disease, left ventricular hypertrophy, global longitudinal strain
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