Search results for: corona disease anxiety
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4708

Search results for: corona disease anxiety

2848 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.

Abstract:

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

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2847 Solid Waste and Its Impact on the Human Health

Authors: Waseem Akram, Hafiz Azhar Ali Khan

Abstract:

Unplanned urbanization together with change in life from simple to more technologically advanced style with flow of rural masses to urban areas has played a vital role in pilling loads of solid wastes in our environment. The cities and towns have expanded beyond boundaries. Even the uncontrolled population expansion has caused the overall environmental burden. Thus, today the indifference remains as one of the biggest trash that has come up due to the non-responsive behavior of the people. Everyday huge amount of solid waste is thrown in the streets, on the roads, parks, and in all those places that are frequently and often visited by the human beings. This behavior based response in many countries of the world has led to serious health concerns and environmental issues. Over 80% of our products that are sold in the market are packed in plastic bags. None of the bags are later recycled but simply become a permanent environment concern that flies, choke lines or are burnt and release toxic gases in the environment or form dumps of heaps. Lack of classification of the daily waste generated from houses and other places lead to worst clogging of the sewerage lines and formation of ponding areas which ultimately favor vector borne disease and sometimes become a cause of transmission of polio virus. Solid waste heaps were checked at different places of the cities. All of the wastes on visual assessments were classified into plastic bags, papers, broken plastic pots, clay pots, steel boxes, wrappers etc. All solid waste dumping sites in the cities and wastes that were thrown outside of the trash containers usually contained wrappers, plastic bags, and unconsumed food products. Insect populations seen in these sites included the house flies, bugs, cockroaches and mosquito larvae breeding in water filled wrappers, containers or plastic bags. The population of the mosquitoes, cockroaches and houseflies were relatively very high in dumping sites close to human population. This population has been associated with cases like dengue, malaria, dysentery, gastro and also to skin allergies during the monsoon and summer season. Thus, dumping of the huge amount of solid wastes in and near the residential areas results into serious environmental concerns, bad smell circulation, and health related issues. In some places, the same waste is burnt to get rid of mosquitoes through smoke which ultimately releases toxic material in the atmosphere. Therefore, a proper environmental strategy is needed to minimize environmental burden and promote concepts of recycled products and thus, reduce the disease burden.

Keywords: solid waste accumulation, disease burden, mosquitoes, vector borne diseases

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2846 To Access the Knowledge, Awareness and Factors Associated With Diabetes Mellitus in Buea, Cameroon

Authors: Franck Acho

Abstract:

This is a chronic metabolic disorder which is a fast-growing global problem with a huge social, health, and economic consequences. It is estimated that in 2010 there were globally 285 million people (approximately 6.4% of the adult population) suffering from this disease. This number is estimated to increase to 430 million in the absence of better control or cure. An ageing population and obesity are two main reasons for the increase. Diabetes mellitus is a chronic heterogeneous metabolic disorder with a complex pathogenesis. It is characterized by elevated blood glucose levels or hyperglycemia, which results from abnormalities in either insulin secretion or insulin action or both. Hyperglycemia manifests in various forms with a varied presentation and results in carbohydrate, fat, and protein metabolic dysfunctions. Long-term hyperglycemia often leads to various microvascular and macrovascular diabetic complications, which are mainly responsible for diabetes-associated morbidity and mortality. Hyperglycemia serves as the primary biomarker for the diagnosis of diabetes as well. Furthermore, it has been shown that almost 50% of the putative diabetics are not diagnosed until 10 years after onset of the disease, hence the real prevalence of global diabetes must be astronomically high. This study was conducted in a locality to access the level of knowledge, awareness and risk factors associated with people leaving with diabetes mellitus. A month before the screening was to be conducted, a health screening in some selected churches and on the local community radio as well as on relevant WhatsApp groups were advertised. A general health talk was delivered by the head of the screening unit to all attendees who were all educated on the procedure to be carried out with benefits and any possible discomforts after which the attendee’s consent was obtained. Evaluation of the participants for any leads to the diabetes selected for the screening was done by taking adequate history and physical examinations such as excessive thirst, increased urination, tiredness, hunger, unexplained weight loss, feeling irritable or having other mood changes, having blurry vision, having slow-healing sores, getting a lot of infections, such as gum, skin and vaginal infections. Out of the 94 participants the finding show that 78 were females and 16 were males, 70.21% of participants with diabetes were between the ages of 60-69yrs.The study found that only 10.63% of respondents declared a good level of knowledge of diabetes. Out of 3 symptoms of diabetes analyzed in this study, high blood sugar (58.5%) and chronic fatigue (36.17%) were the most recognized. Out of 4 diabetes risk factors analyzed in this study, obesity (21.27%) and unhealthy diet (60.63%) were the most recognized diabetes risk factors, while only 10.6% of respondents indicated tobacco use. The diabetic foot was the most recognized diabetes complication (50.57%), but some the participants indicated vision problems (30.8%),or cardiovascular diseases (20.21%) as diabetes complications.

Keywords: diabetes mellitus, non comunicable disease, general health talk, hyperglycemia

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2845 Mechanism of Modeling the Level of Bcr-Abl Oncoprotein by Ubiquitin-Proteasome System in Chronic Myeloid Leukemia

Authors: Svitlana Antonenko, Gennady Telegeev

Abstract:

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

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2844 On the Optimality Assessment of Nano-Particle Size Spectrometry and Its Association to the Entropy Concept

Authors: A. Shaygani, R. Saifi, M. S. Saidi, M. Sani

Abstract:

Particle size distribution, the most important characteristics of aerosols, is obtained through electrical characterization techniques. The dynamics of charged nano-particles under the influence of electric field in electrical mobility spectrometer (EMS) reveals the size distribution of these particles. The accuracy of this measurement is influenced by flow conditions, geometry, electric field and particle charging process, therefore by the transfer function (transfer matrix) of the instrument. In this work, a wire-cylinder corona charger was designed and the combined field-diffusion charging process of injected poly-disperse aerosol particles was numerically simulated as a prerequisite for the study of a multi-channel EMS. The result, a cloud of particles with non-uniform charge distribution, was introduced to the EMS. The flow pattern and electric field in the EMS were simulated using computational fluid dynamics (CFD) to obtain particle trajectories in the device and therefore to calculate the reported signal by each electrometer. According to the output signals (resulted from bombardment of particles and transferring their charges as currents), we proposed a modification to the size of detecting rings (which are connected to electrometers) in order to evaluate particle size distributions more accurately. Based on the capability of the system to transfer information contents about size distribution of the injected particles, we proposed a benchmark for the assessment of optimality of the design. This method applies the concept of Von Neumann entropy and borrows the definition of entropy from information theory (Shannon entropy) to measure optimality. Entropy, according to the Shannon entropy, is the ''average amount of information contained in an event, sample or character extracted from a data stream''. Evaluating the responses (signals) which were obtained via various configurations of detecting rings, the best configuration which gave the best predictions about the size distributions of injected particles, was the modified configuration. It was also the one that had the maximum amount of entropy. A reasonable consistency was also observed between the accuracy of the predictions and the entropy content of each configuration. In this method, entropy is extracted from the transfer matrix of the instrument for each configuration. Ultimately, various clouds of particles were introduced to the simulations and predicted size distributions were compared to the exact size distributions.

Keywords: aerosol nano-particle, CFD, electrical mobility spectrometer, von neumann entropy

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2843 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

Abstract:

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

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2842 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

Abstract:

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

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2841 Mapping Network Connection of Personality Traits and Psychiatric Symptoms in Chinese Adolescents

Authors: Yichao Lv, Minmin Cai, Yanqiang Tao, Xinyuan Zou, Chao Zhang, Xiangping Liu

Abstract:

Objective: This study aims to explore the network structure of personality traits and mental health and identify key factors for effective intervention strategies. Methods: All participants (N = 6,067; 3,368 females) underwent the Eysenck Personality Scale (EPQ) to measure personality traits and the Symptom Self-rating Scale (SCL-90) to measure psychiatric symptoms. Using the mean value of the SCL-90 total score plus one standard deviation as the cutoff, 854 participants (14.08%; 528 females) were categorized as individuals exhibiting potential psychological symptoms and were included in the follow-up network analysis. The structure and bridge centrality of the network for dimensions of EPQ and SCL-90 were estimated. Results: Between the EPQ and SCL-90, psychoticism (P), extraversion (E), and neuroticism (N) showed the strongest positive correlations with somatization (Som), interpersonal sensitivity (IS), and hostility (Hos), respectively. Extraversion (E), somatization (Som), and anxiety (Anx) were identified as the most important bridge factors influencing the overall network. Conclusions: This study explored the network structure and complex connections between mental health and personality traits from a network perspective, providing potential targets for intervening in adolescent personality traits and mental health.

Keywords: EPQ, SCL-90, Chinese adolescents, network analysis

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2840 Eros and Postmodern Nihilism in Don Delillo’s Zero K (2016): A Psychoanalytical Reading

Authors: Nouioua Wafa

Abstract:

It is broadly accepted that the existence of postmodern individuals is distinguished by a predominant presence of skepticism, anxiety and loneliness. This social unrest is the consequence of a drastic shift in how reality and meaning are conceived, which has been replaced by something that is referred to in media theory and criticism as hyperreality. The purpose of this paper is to investigate the hyperreality that exists in the postmodern nihilistic American community that Don Delillo depicts in Zero K (2016) through the use of Jean Baudrillard's notions of Simulacra and Simulations. It is a troubled technological late capitalist society obsessed with immortality and fear of demise, and ergo it is an appropriate reading to implement Sigmund Freud’s theory of life drive (Eros), which refers to the life instinct fundamental to all humans and the urge to support productivity and construction. The results obtained from a qualitative analysis of Zero K indicate the presence of a clash between the character’s life drive and fear of mortality. In an effort to escape loneliness and death, the character Ross Lockhart undergoes, after a moment of hesitation, cryonic freezing in the convergence to preserve his life as well as that of his wife Artis, yet his son Jeffery is firmly convinced of the uselessness of combating the inevitable death.

Keywords: Don DeLillo, Eros, postmodernism Nihilism, Zero K

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2839 The Type II Immune Response in Acute and Chronic Pancreatitis Mediated by STAT6 in Murine

Authors: Hager Elsheikh

Abstract:

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

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2838 Genetic and Virulence Diversity among Alternaria carthami Isolates of India

Authors: Garima Anand, Rupam Kapoor

Abstract:

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

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2837 Eros and Postmodern Nihilism in Don Delillo’s Zero K (2016): A Psychoanalytical Reading

Authors: Wafa Nouioua

Abstract:

It is broadly accepted that the existence of postmodern individuals is distinguished by a predominant presence of skepticism, anxiety and loneliness. This social unrest is the consequence of a drastic shift in how reality and meaning are conceived, which has been replaced by something that is referred to in media theory and criticism as hyperreality. The purpose of this paper is to investigate the hyperreality that exists in the postmodern nihilistic American community that Don Delillo depicts in Zero K (2016) through the use of Jean Baudrillard notions of Simulacra and Simulations. It is a troubled technological late capitalist society obsessed with immortality and fear of demise, ergo it is an appropriate reading to implement Sigmund Freud’s theory of life drive (Eros), which refers to the life instinct fundamental to all humans and the urge to support productivity and construction. The results obtained from a qualitative analysis of Zero K indicate the presence of a clash between the character’s life drive and fear of mortality. In an effort to escape loneliness and death, the character Ross Lockhart undergoes, after a moment of hesitation, cryonic freezing in the convergence to preserve his life as well as that of his wife Artis, yet his son Jeffery is firmly convinced of the uselessness of combating the inevitable death.

Keywords: Don Dellilo, Eros, Postmodernism Nihilism, Zero K

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2836 Paediatric Motor Difficulties and Internalising Problems: An Integrative Review on the Environmental Stress Hypothesis

Authors: Noah Erskine, Jaime Barratt, John Cairney

Abstract:

The current study aims to provide an in-depth analysis and extension of the Environmental Stress Hypothesis (ESH) framework, focusing on the complex interplay between poor motor skills and internalising problems like anxiety and depression. Using an integrative research review methodology, this study synthesizes findings from 38 articles, both empirical and theoretical, building upon the foundational work of the model. The hypothesis posits that poor motor skills serve as a primary stressor, leading to internalising problems through various secondary stressors. A rigorous comparison of data was conducted, considering study design, findings, and methodologies - while giving special attention to variables such as age, sex, and comorbidities. The study also enhances the ESH framework by introducing resource buffers, including optimism and familial support, as additional influencing factors. This multi-level approach yields a more nuanced and comprehensive ESH framework, highlighting the need for future studies to consider intersectional variables and how they may vary across various life stages.

Keywords: motor coordination, mental health, developmental coordination disorders, paediatric comorbidities, obesity, peer problems

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2835 Targeting Matrix Metalloprotease-9 to Reduce Coronary Artery Manifestations of Kawasaki’s Disease

Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

Abstract:

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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2834 Pulmonary Disease Identification Using Machine Learning and Deep Learning Techniques

Authors: Chandu Rathnayake, Isuri Anuradha

Abstract:

Early detection and accurate diagnosis of lung diseases play a crucial role in improving patient prognosis. However, conventional diagnostic methods heavily rely on subjective symptom assessments and medical imaging, often causing delays in diagnosis and treatment. To overcome this challenge, we propose a novel lung disease prediction system that integrates patient symptoms and X-ray images to provide a comprehensive and reliable diagnosis.In this project, develop a mobile application specifically designed for detecting lung diseases. Our application leverages both patient symptoms and X-ray images to facilitate diagnosis. By combining these two sources of information, our application delivers a more accurate and comprehensive assessment of the patient's condition, minimizing the risk of misdiagnosis. Our primary aim is to create a user-friendly and accessible tool, particularly important given the current circumstances where many patients face limitations in visiting healthcare facilities. To achieve this, we employ several state-of-the-art algorithms. Firstly, the Decision Tree algorithm is utilized for efficient symptom-based classification. It analyzes patient symptoms and creates a tree-like model to predict the presence of specific lung diseases. Secondly, we employ the Random Forest algorithm, which enhances predictive power by aggregating multiple decision trees. This ensemble technique improves the accuracy and robustness of the diagnosis. Furthermore, we incorporate a deep learning model using Convolutional Neural Network (CNN) with the RestNet50 pre-trained model. CNNs are well-suited for image analysis and feature extraction. By training CNN on a large dataset of X-ray images, it learns to identify patterns and features indicative of lung diseases. The RestNet50 architecture, known for its excellent performance in image recognition tasks, enhances the efficiency and accuracy of our deep learning model. By combining the outputs of the decision tree-based algorithms and the deep learning model, our mobile application generates a comprehensive lung disease prediction. The application provides users with an intuitive interface to input their symptoms and upload X-ray images for analysis. The prediction generated by the system offers valuable insights into the likelihood of various lung diseases, enabling individuals to take appropriate actions and seek timely medical attention. Our proposed mobile application has significant potential to address the rising prevalence of lung diseases, particularly among young individuals with smoking addictions. By providing a quick and user-friendly approach to assessing lung health, our application empowers individuals to monitor their well-being conveniently. This solution also offers immense value in the context of limited access to healthcare facilities, enabling timely detection and intervention. In conclusion, our research presents a comprehensive lung disease prediction system that combines patient symptoms and X-ray images using advanced algorithms. By developing a mobile application, we provide an accessible tool for individuals to assess their lung health conveniently. This solution has the potential to make a significant impact on the early detection and management of lung diseases, benefiting both patients and healthcare providers.

Keywords: CNN, random forest, decision tree, machine learning, deep learning

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2833 An Educational Program Based on Health Belief Model to Prevent of Non-alcoholic Fatty Liver Disease Among Iranian Women

Authors: Arezoo Fallahi

Abstract:

Background and purpose: Non-alcoholic fatty liver is one of the most common liver disorders, which, as the most important cause of death from liver disease, has unpleasant consequences and complications. The aim of this study was to investigate the effect of an educational intervention based on a health belief model to prevent non-alcoholic fatty liver among women. Materials and Methods: This experimental study was performed among 110 women referring to comprehensive health service centers in Malayer City, west of Iran, in 2023. Using the available sampling method, 110 Participants were divided into experimental and control groups. The data collection tool included demographic characteristics and a questionnaire based on the health belief model. In The experimental group, three one-hour training sessions were conducted in the form of pamphlets, lectures and group discussions. Data were analyzed using SPSS software version 21, by correlation tests, paired t-tests independent t-tests. Results: The mean age of participants was 38.07±6.28 years, and Most of the participants were middle-aged, married, housewives with academic education, middle-income and overweight. After the educational intervention, the mean scores of the constructs include perceived sensitivity (p=0.01), perceived severity (p=0.01), perceived benefits (p=0.01), guidance for internal (p=0.01) and external action (p=0.01), and perceived self-efficacy (p=0.01) in the experimental group were significantly higher than the control group. The score of perceived barriers in the experimental group decreased after training. The perceived obstacles score in the test group decreased after the training (15.2 ± 3.9 v.s 11.2 ± 3.3, (p<0.01). Conclusion: The findings of the study showed that the design and implementation of educational programs based on the constructs of the health belief model can be effective in preventing women from developing higher levels of non-alcoholic fatty liver.

Keywords: health, education, believe, behaviour

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2832 The Fast Diagnosis of Acanthamoeba Keratitis Using Real-Time PCR Assay

Authors: Fadime Eroglu

Abstract:

Acanthamoeba genus belongs to kingdom protozoa, and it is known as free-living amoebae. Acanthamoeba genus has been isolated from human bodies, swimming pools, bottled mineral water, contact lens solutions, dust, and soil. The members of the genus Acanthamoeba causes Acanthamoeba Keratitis which is a painful sight-threatening disease of the eyes. In recent years, the prevalence of Acanthamoeba keratitis has been high rate reported. The eight different Acanthamoeba species are known to be effective in Acanthamoeba keratitis. These species are Acanthamoeba castellanii, Acanthamoeba polyphaga, Acanthamoeba griffini, Acanthamoeba hatchetti, Acanthamoeba culbertsoni and Acanhtamoeba rhysodes. The conventional diagnosis of Acanthamoeba Keratitis has relied on cytological preparations and growth of Acanthamoeba in culture. However molecular methods such as real-time PCR has been found to be more sensitive. The real-time PCR has now emerged as an effective method for more rapid testing for the diagnosis of infectious disease in decade. Therefore, a real-time PCR assay for the detection of Acanthamoeba keratitis and Acanthamoeba species have been developed in this study. The 18S rRNA sequences from Acanthamoeba species were obtained from National Center for Biotechnology Information and sequences were aligned with MEGA 6 programme. Primers and probe were designed using Custom Primers-OligoPerfectTMDesigner (ThermoFisherScientific, Waltham, MA, USA). They were also assayed for hairpin formation and degree of primer-dimer formation with Multiple Primer Analyzer ( ThermoFisherScientific, Watham, MA, USA). The eight different ATCC Acanthamoeba species were obtained, and DNA was extracted using the Qiagen Mini DNA extraction kit (Qiagen, Hilden, Germany). The DNA of Acanthamoeba species were analyzed using newly designed primer and probe set in real-time PCR assay. The early definitive laboratory diagnosis of Acanthamoeba Keratitis and the rapid initiation of suitable therapy is necessary for clinical prognosis. The results of the study have been showed that new primer and probes could be used for detection and distinguish for Acanthamoeba species. These new developing methods are helpful for diagnosis of Acanthamoeba Keratitis.

Keywords: Acathamoeba Keratitis, Acanthamoeba species, fast diagnosis, Real-Time PCR

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2831 SUMOylation Enhances Nurr1/1a Mediated Transactivation in a Neuronal Cell Type

Authors: Jade Edey, Andrew Bennett, Gareth Hathway

Abstract:

Nuclear receptor-related 1 protein (also known as Nurr1 or NR4A2) is an orphan nuclear receptor which plays a vital role in the development, survival and maintenance of dopaminergic (DA) neurons particularly in the substantia nigra (SN). Increasing research has investigated Nurr1’s additional role within microglia and astrocytes where it has been suggested to act as a negative regulator of inflammation; potentially offering neuroprotection. Considering both DA neurodegeneration and neuroinflammation are commonly accepted constituents of Parkinson’s Disease (PD), understanding the mechanisms by which Nurr1 regulates inflammatory processes could provide an attractive therapeutic target. Nurr1 regulates inflammation via a transrepressive mechanism possibly dependent upon SUMOylation. In addition, Nurr1 can transactivate numerous genes involved in DA synthesis, such as Tyrosine Hydroxylase (TH). A C-terminal splice variant of Nurr1, Nurr-1a, has been reported in both neuronal and glial cells. However, research into its transcriptional activity is minimal. We employed in vitro methods such as SUMO-Pulldown experiments alongside Luciferase reporter assays to investigate the SUMOylation status and transactivation capabilities of Nurr1 and Nurr-1a respectively. The SUMO-Pulldown assay demonstrated Nurr-1a undergoes significantly more SUMO modification than its full-length variant. Consequently, despite having less transcriptional activation than Nurr1, Nurr1a may play a more prominent role in repression of microglial inflammation. Contrary to published literature we also identified that SUMOylation enhances transcriptional activation by Nurr1 and Nurr1a. SUMOylation-dependent increases in Nurr1 and Nurr1a transcriptional activation were only evident in neuronal SHSY5Y cells but not in HEK293 cells. This research provides novel insight into the regulation of Nurr-1a and indicates differential effects of SUMOylation dependent regulation in neuronal and inflammatory cells.

Keywords: nuclear receptors, Parkinson’s disease, inflammation, transcriptional regulation

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2830 Changed Behavior of the Porcine Hemagglutinating Encephalomyelitis Virus (Betacoronavirus) in Respiratory Epithelial Cells

Authors: Ateeqa Aslam, Hans J. Nauwynck

Abstract:

Porcine hemagglutinating encephalomyelitis virus (PHEV) is a betacoronavirus that has been studied in the past as a cause of vomiting and wasting disease (VWD) in young piglets (<3 weeks). Nowadays, the virus is still circulating on most farms in Belgium, but there are no descriptions anymore of VWD. Therefore, we are interested in differences between the old and new strains. We compared the replication kinetics of the old well-studied strain VW572 (1972) and the recent isolate P412 (2020) in a susceptible continuous cell line (RPD cells) and in primary porcine respiratory epithelial cells (PoRECs). The RPD cell line was inoculated with each PHEV strain at an m.o.i. of 1 the supernatant was collected, and the cells were fixed at different time points post-inoculation. The supernatant was titrated (extracellular virus titer), and the infected cells were revealed by immunofluorescence staining and quantitated by fluorescence microscopy. We found that VW572 replicated better in the RPD cell line at earlier time points when compared to P412. Porcine respiratory epithelial cells (PoREC) were isolated, grown at air-liquid interphase in transwells and inoculated with both strains of PHEV at a virus titer of 106.6TCID50 per 200 µl either at the apical side or at the basal side of the cells. At different time points after inoculation, the transwells were fixed and stained for infected cells. VW572 preferentially infected the epithelial cells via the basolateral side of porcine nasal epithelial cells, whereas P412 preferred the apical side. These findings suggest that there has been an evolution of PHEV in its interaction with the respiratory epithelial cells. In the future, more virus strains will be enclosed and the tropism of the strains for different neuronal cell types will be examined for the change in virus neurotropism.

Keywords: porcine hemagglutinating encephalomyelitis virus (PHEV), primary porcine respiratory epithelial cells (PoRECs), virus tropism, vomiting and wasting disease (VWD)

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2829 Development of Monoclonal Antibodies against the Acute Hepatopancreatic Necrosis Disease Toxins

Authors: Naveen Kumar B. T., Anuj Tyagi, Niraj Kumar Singh, Visanu Boonyawiwat, Shanthanagouda A. H., Orawan Boodde, Shankar K. M., Prakash Patil, Shubhkaramjeet Kaur

Abstract:

Since 2009, Acute Hepatopancreatic Necrosis Disease (AHPND) outbreaks have increased rapidly, and these have led to the major economic losses to the global shrimp industry. In comparison to other treatments, passive immunity and monoclonal antibody (MAb) based farmer level kit have proved their importance in controlling and treating the diseases in the shrimp industry. In the present study, MAbs were produced against the recombinant PirB protein Vibrio parahaemolyticus strain causing AHPND. Briefly, Balb/C mice were immunized with rPirB at 15 days interval, and antibody titer was determined by ELISA. Spleen cells from mice showing high antibody titer were fused with SP2O myeloma cells for hybridoma production. Among 130 hybridomas, four showed high antibody titer and positive reactivity in an immunoblot assay. In Western blot assay, three out of four MAbs (4C4, 2C2 and 4G3) showed reactivity to rPirB protein. However, in the natural host, only Mab clone 4G3 show strong reactivity (with a strain of V. parahemolyticus causing EMS/AHPND). These clones also showed reactivity with less than 20 kDa proteins in AHPND free V. parahaemolyticus (Thailand stain). Further, on from MAb 4G3 clone, four panels of single cell MAbs clones (G3F5, G3B8, G3H2, and G3D6) were produced of which three showed strong positive reactivity to rPirB protein in the Western blot. These MAbs have potential for controlling and prevention of the AHPND through passive immunity and development of filed level rapid diagnostic kits.

Keywords: shrimp, economic loss, AHPND, MAb

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2828 Mindfulness Meditation in Higher Education

Authors: Steve Haberlin

Abstract:

United States college students are experiencing record-high stress and anxiety rates, and due to technological advances, there are more distractions in the classroom. With these challenges comes the need to explore additional, non-traditional pedagogical strategies that can help students de-stress, become centered, and feel more deeply connected to content. In addition, embedding contemplative practices, such as mindfulness meditation, in the higher education classroom could assist faculty in presenting a more holistic education that encourages students to develop self-awareness, emotional intelligence, compassion, interconnectedness, and other “non-academic” qualities. Brief meditation may help students de-stress, focus, and connect. A facilitation guide could also help faculty implement classroom meditation practices; however, additional research is needed to determine how to best train faculty, what meditation techniques work best with students, and how to handle resistance. In this paper, a two-phase study is presented that involves a mindfulness meditation intervention with 180 undergraduate students at a private college in the southeastern United States. Data were collected through qualitative surveys and journaling and analyzed for themes. Findings included a majority of students reporting improved calm, reduced stress, and increased focus and ability to transition to classroom instruction.

Keywords: college students, higher education, mindfulness meditation, stress

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2827 Clinical Relevance of TMPRSS2-ERG Fusion Marker for Prostate Cancer

Authors: Shalu Jain, Anju Bansal, Anup Kumar, Sunita Saxena

Abstract:

Objectives: The novel TMPRSS2:ERG gene fusion is a common somatic event in prostate cancer that in some studies is linked with a more aggressive disease phenotype. Thus, this study aims to determine whether clinical variables are associated with the presence of TMPRSS2:ERG-fusion gene transcript in Indian patients of prostate cancer. Methods: We evaluated the clinical variables with presence and absence of TMPRSS2:ERG gene fusion in prostate cancer and BPH association of clinical patients. Patients referred for prostate biopsy because of abnormal DRE or/and elevated sPSA were enrolled for this prospective clinical study. TMPRSS2:ERG mRNA copies in samples were quantified using a Taqman chemistry by real time PCR assay in prostate biopsy samples (N=42). The T2:ERG assay detects the gene fusion mRNA isoform TMPRSS2 exon1 to ERG exon4. Results: Histopathology report has confirmed 25 cases as prostate cancer adenocarcinoma (PCa) and 17 patients as benign prostate hyperplasia (BPH). Out of 25 PCa cases, 16 (64%) were T2: ERG fusion positive. All 17 BPH controls were fusion negative. The T2:ERG fusion transcript was exclusively specific for prostate cancer as no case of BPH was detected having T2:ERG fusion, showing 100% specificity. The positive predictive value of fusion marker for prostate cancer is thus 100% and the negative predictive value is 65.3%. The T2:ERG fusion marker is significantly associated with clinical variables like no. of positive cores in prostate biopsy, Gleason score, serum PSA, perineural invasion, perivascular invasion and periprostatic fat involvement. Conclusions: Prostate cancer is a heterogeneous disease that may be defined by molecular subtypes such as the TMPRSS2:ERG fusion. In the present prospective study, the T2:ERG quantitative assay demonstrated high specificity for predicting biopsy outcome; sensitivity was similar to the prevalence of T2:ERG gene fusions in prostate tumors. These data suggest that further improvement in diagnostic accuracy could be achieved using a nomogram that combines T2:ERG with other markers and risk factors for prostate cancer.

Keywords: prostate cancer, genetic rearrangement, TMPRSS2:ERG fusion, clinical variables

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2826 Evaluation of the Risk Factors on the Incidence of Adjacent Segment Degeneration After Anterior Neck Discectomy and Fusion

Authors: Sayyed Mostafa Ahmadi, Neda Raeesi

Abstract:

Background and Objectives: Cervical spondylosis is a common problem that affects the adult spine and is the most common cause of radiculopathy and myelopathy in older patients. Anterior discectomy and fusion is a well-known technique in degenerative cervical disc disease. However, one of the late undesirable complications is adjacent disc degeneration, which affects about 91% of patients in ten years. Many factors can be effective in causing this complication, but some are still debatable. Discovering these risk factors and eliminating them can improve the quality of life. Methods: This is a retrospective cohort study. All patients who underwent anterior discectomy and fusion surgery in the neurosurgery ward of Imam Khomeini Hospital between 2013 and 2016 were evaluated. Their demographic information was collected. All patients were visited and examined for radiculopathy, myelopathy, and muscular force. At the same visit, all patients were asked to have a facelift, and neck profile, as well as a neck MRI(General Tesla 3). Preoperative graphs were used to measure the diameter of the cervical canal(Pavlov ratio) and to evaluate sagittal alignment(Cobb Angle). Preoperative MRI of patients was reviewed for anterior and posterior longitudinal ligament calcification. Result: In this study, 57 patients were studied. The mean age of patients was 50.63 years, and 49.1% were male. Only 3.5% of patients had anterior and posterior longitudinal ligament calcification. Symptomatic ASD was observed in 26.6%. The X-rays and MRIs showed evidence of 80.7% radiological ASD. Among patients who underwent one-level surgery, 20% had symptomatic ASD, but among patients who underwent two-level surgery, the rate of ASD was 50%.In other words, the higher the number of surfaces that are operated and fused, the higher the probability of symptomatic ASD(P-value <0.05). The X-rays and MRIs showed 80.7% of radiological ASD. Among patients who underwent surgery at one level, 78% had radiological ASD, and this number was 92% among patients who underwent two-level surgery(P-value> 0.05). Demographic variables such as age, sex, height, weight, and BMI did not have a significant effect on the incidence of radiological ASD(P-value> 0.05), but sex and height were two influential factors on symptomatic ASD(P-value <0.05). Other related variables such as family history, smoking and exercise also have no significant effect(P-value> 0.05). Radiographic variables such as Pavlov ratio and sagittal alignment were also unaffected by the incidence of radiological and symptomatic ASD(P-value> 0.05). The number of surgical surfaces and the incidence of anterior and posterior longitudinal ligament calcification before surgery also had no statistically significant effect(P-value> 0.05). In the study of the ability of the neck to move in different directions, none of these variables are statistically significant in the two groups with radiological and symptomatic ASD and the non-affected group(P-value> 0.05). Conclusion: According to the findings of this study, this disease is considered to be a multifactorial disease. The incidence of radiological ASD is much higher than symptomatic ASD (80.7% vs. 26.3%) and sex, height and number of fused surfaces are the only factors influencing the incidence of symptomatic ASD and no variable influences radiological ASD.

Keywords: risk factors, anterior neck disectomy and fusion, adjucent segment degeneration, complication

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2825 The Role of Piceatannol in Counteracting Glyceraldehyde-3-Phosphate Dehydrogenase Aggregation and Nuclear Translocation

Authors: Joanna Gerszon, Aleksandra Rodacka

Abstract:

In the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, protein and peptide aggregation processes play a vital role in contributing to the formation of intracellular and extracellular protein deposits. One of the major components of these deposits is the oxidatively modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Therefore, the purpose of this research was to answer the question whether piceatannol, a stilbene derivative, counteracts and/or slows down oxidative stress-induced GAPDH aggregation. The study also aimed to determine if this natural occurring compound prevents unfavorable nuclear translocation of GAPDH in hippocampal cells. The isothermal titration calorimetry (ITC) analysis indicated that one molecule of GAPDH can bind up to 8 molecules of piceatannol (7.3 ± 0.9). As a consequence of piceatannol binding to the enzyme, the loss of activity was observed. Parallel with GAPDH inactivation the changes in zeta potential, and loss of free thiol groups were noted. Nevertheless, the ligand-protein binding does not influence the secondary structure of the GAPDH. Precise molecular docking analysis of the interactions inside the active center allowed to presume that these effects are due to piceatannol ability to assemble a covalent binding with nucleophilic cysteine residue (Cys149) which is directly involved in the catalytic reaction. Molecular docking also showed that simultaneously 11 molecules of ligand can be bound to dehydrogenase. Taking into consideration obtained data, the influence of piceatannol on level of GAPDH aggregation induced by excessive oxidative stress was examined. The applied methods (thioflavin-T binding-dependent fluorescence as well as microscopy methods - transmission electron microscopy, Congo Red staining) revealed that piceatannol significantly diminishes level of GAPDH aggregation. Finally, studies involving cellular model (Western blot analyses of nuclear and cytosolic fractions and confocal microscopy) indicated that piceatannol-GAPDH binding prevents GAPDH from nuclear translocation induced by excessive oxidative stress in hippocampal cells. In consequence, it counteracts cell apoptosis. These studies demonstrate that by binding with GAPDH, piceatannol blocks cysteine residue and counteracts its oxidative modifications, that induce oligomerization and GAPDH aggregation as well as it prevents hippocampal cells from apoptosis by retaining GAPDH in the cytoplasm. All these findings provide a new insight into the role of piceatannol interaction with GAPDH and present a potential therapeutic strategy for some neurological disorders related to GAPDH aggregation. This work was supported by the by National Science Centre, Poland (grant number 2017/25/N/NZ1/02849).

Keywords: glyceraldehyde-3-phosphate dehydrogenase, neurodegenerative disease, neuroprotection, piceatannol, protein aggregation

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2824 Experience of Two Major Research Centers in the Diagnosis of Cardiac Amyloidosis from Transthyretin

Authors: Ioannis Panagiotopoulos, Aristidis Anastasakis, Konstantinos Toutouzas, Ioannis Iakovou, Charalampos Vlachopoulos, Vasilis Voudris, Georgios Tziomalos, Konstantinos Tsioufis, Efstathios Kastritis, Alexandros Briassoulis, Kimon Stamatelopoulos, Alexios Antonopoulos, Paraskevi Exadaktylou, Evanthia Giannoula, Anastasia Katinioti, Maria Kalantzi, Evangelos Leontiadis, Eftychia Smparouni, Ioannis Malakos, Nikolaos Aravanis, Argyrios Doumas, Maria Koutelou

Abstract:

Introduction: Cardiac amyloidosis from Transthyretin (ATTR-CA) is an infiltrative disease characterized by the deposition of pathological transthyretin complexes in the myocardium. This study describes the characteristics of patients diagnosed with ATTR-CA from 2019 until present at the Nuclear Medicine Department of Onassis Cardiac Surgery Center and AHEPA Hospital. These centers have extensive experience in amyloidosis and modern technological equipment for its diagnosis. Materials and Methods: Records of consecutive patients (N=73) diagnosed with any type of amyloidosis were collected, analyzed, and prospectively followed. The diagnosis of amyloidosis was made using specific myocardial scintigraphy with Tc-99m DPD. Demographic characteristics, including age, gender, marital status, height, and weight, were collected in a database. Clinical characteristics, such as amyloidosis type (ATTR and AL), serum biomarkers (BNP, troponin), electrocardiographic findings, ultrasound findings, NYHA class, aortic valve replacement, device implants, and medication history, were also collected. Some of the most significant results are presented. Results: A total of 73 cases (86% male) were diagnosed with amyloidosis over four years. The mean age at diagnosis was 82 years, and the main symptom was dyspnea. Most patients suffered from ATTR-CA (65 vs. 8 with AL). Out of all the ATTR-CA patients, 61 were diagnosed with wild-type and 2 with two rare mutations. Twenty-eight patients had systemic amyloidosis with extracardiac involvement, and 32 patients had a history of bilateral carpal tunnel syndrome. Four patients had already developed polyneuropathy, and the diagnosis was confirmed by DPD scintigraphy, which is known for its high sensitivity. Among patients with isolated cardiac involvement, only 6 had left ventricular ejection fraction below 40%. The majority of ATTR patients underwent tafamidis treatment immediately after diagnosis. Conclusion: In conclusion, the experiences shared by the two centers and the continuous exchange of information provide valuable insights into the diagnosis and management of cardiac amyloidosis. Clinical suspicion of amyloidosis and early diagnostic approach are crucial, given the availability of non-invasive techniques. Cardiac scintigraphy with DPD can confirm the presence of the disease without the need for a biopsy. The ultimate goal still remains continuous education and awareness of clinical cardiologists so that this systemic and treatable disease can be diagnosed and certified promptly and treatment can begin as soon as possible.

Keywords: amyloidosis, diagnosis, myocardial scintigraphy, Tc-99m DPD, transthyretin

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2823 Analyzing Doctors’ Knowledge of the United Kingdom Chief Medical Officer's Guidelines for Physical Activity: Survey of Secondary Care Doctors in a District General Hospital

Authors: Alexandra Von Guionneau, William Sloper, Charlotte Burford

Abstract:

The benefits of exercise for the prevention and management of chronic disease are well established and the importance of primary care practitioners in promoting exercise is becoming increasingly recognized. However, those with severe manifestations of the chronic disease are managed in a secondary care setting. Secondary care practitioners, therefore, have a role to play in promoting physical activity. Methods: In order to assess secondary care doctors’ knowledge of the Chief Medical Officer’s guidelines for physical activity, a 12-question survey was administered to staff working in a district general hospital in South England during team and unit meetings. Questions related to knowledge of the current guidelines for both 19 - 64 year olds and older adults (65 years and above), barriers to exercise discussion or prescription and doctors’ own exercise habits. Responses were collected anonymously and analyzed using SPSS Version 24.0. Results: 96 responses were collected. Doctors taking part in the survey ranged from foundation years (26%) to consultants (40%). 17.7% of participants knew the guidelines for moderate intensity activity for 19 - 64 year olds. Only one participant knew all of the guidance for both 19 - 64 year olds and older adults. While 71.6% of doctors felt they were adequately informed about how to exercise, only 45.6% met the minimum recommended guidance for moderate intensity activity. Conclusion: More work is needed to promote the physical activity guidelines and exercise prescription to doctors working within a secondary care setting. In addition, doctors require more support to personally meet the recommended minimum level of physical activity.

Keywords: exercise is medicine, exercise prescription, physical activity guidelines, exercise habits

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2822 Epidemiology of Cutaneous Malignant Melanoma in Pakistan: Incidence, Clinical Subtypes, Tumor Stage and Localization

Authors: Warda Jabeen, Romaisa Shamim Khan, Osama Shakeel, Ahmed Faraz Bhatti, Raza Hussain

Abstract:

Background: The worldwide incidence of cutaneous melanoma (CM) has been on the rise over the past few decades. Primary prevention and early treatment remain the focus of management to reduce the burden of disease. This entails identification of risk factors to prompt early diagnosis. In Pakistan, there is a scarcity of clinico-pathological data relating to cutaneous malignant melanoma. Objective: The purpose of this study was to analyze the epidemiological and clinical characteristics of patients presenting with cutaneous malignant melanoma in Pakistan, and to compare the results with other studies. Method: Shaukat Khanum Memorial Cancer Hospital and Research Centre is currently the only dedicated cancer hospital in the country, accepting patients from all over Pakistan. Majority of the patients, however, belong to the northern half of the country. From the recorded data of the hospital, all cutaneous melanoma cases were identified and evaluated. Results: Between 1997 and 2017, a total of 169 cutaneous melanoma patients were registered at Shaukat Khanum. Mean age was 47.5 years. The highest incidence of melanoma was seen in the age group 40-59 years (n=69, 40.8%). Most commonly reported clinical subtype was unspecified melanoma (n=154, 91%). Amongst those in which T stage was reported, the most frequently observed T-stage at presentation was T4 (n=23, 13.6%). With regards to body distribution, in our study CM was seen most commonly in the lower limb including the hip. The yearly incidence of melanoma has increased/remained stable from 2007 to 2017. Conclusion: cutaneous malignant melanoma is a fairly common disease in Pakistan. Patients tend to present at a more advanced stage as compared to patients in developed countries. Identification of risk factors and tumor characteristics is therefore of paramount importance to deal with these patients.

Keywords: epidemiology of cutaneous malignant melanoma, cutaneous malignant melanoma, Pakistan, skin cancer

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2821 Bioinformatics Identification of Rare Codon Clusters in Proteins Structure of HBV

Authors: Abdorrasoul Malekpour, Mohammad Ghorbani Mojtaba Mortazavi, Mohammadreza Fattahi, Mohammad Hassan Meshkibaf, Ali Fakhrzad, Saeid Salehi, Saeideh Zahedi, Amir Ahmadimoghaddam, Parviz Farzadnia Dr., Mohammadreza Hajyani Asl Bs

Abstract:

Hepatitis B as an infectious disease has eight main genotypes (A–H). The aim of this study is to Bioinformatically identify Rare Codon Clusters (RCC) in proteins structure of HBV. For detection of protein family accession numbers (Pfam) of HBV proteins; used of uni-prot database and Pfam search tool were used. Obtained Pfam IDs were analyzed in Sherlocc program and RCCs in HBV proteins were detected. In further, the structures of TrEMBL entries proteins studied in PDB database and 3D structures of the HBV proteins and locations of RCCs were visualized and studied using Swiss PDB Viewer software. Pfam search tool have found nine significant hits and 0 insignificant hits in 3 frames. Results of Pfams studied in the Sherlocc program show this program not identified RCCs in the external core antigen (PF08290) and truncated HBeAg protein (PF08290). By contrast the RCCs become identified in Hepatitis core antigen (PF00906) Large envelope protein S (PF00695), X protein (PF00739), DNA polymerase (viral) N-terminal domain (PF00242) and Protein P (Pf00336). In HBV genome, seven RCC identified that found in hepatitis core antigen, large envelope protein S and DNA polymerase proteins and proteins structures of TrEMBL entries sequences that reported in Sherlocc program outputs are not complete. Based on situation of RCC in structure of HBV proteins, it suggested those RCCs are important in HBV life cycle. We hoped that this study provide a new and deep perspective in protein research and drug design for treatment of HBV.

Keywords: rare codon clusters, hepatitis B virus, bioinformatic study, infectious disease

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2820 COVID-19 Laws and Policy: The Use of Policy Surveillance For Better Legal Preparedness

Authors: Francesca Nardi, Kashish Aneja, Katherine Ginsbach

Abstract:

The COVID-19 pandemic has demonstrated both a need for evidence-based and rights-based public health policy and how challenging it can be to make effective decisions with limited information, evidence, and data. The O’Neill Institute, in conjunction with several partners, has been working since the beginning of the pandemic to collect, analyze, and distribute critical data on public health policies enacted in response to COVID-19 around the world in the COVID-19 Law Lab. Well-designed laws and policies can help build strong health systems, implement necessary measures to combat viral transmission, enforce actions that promote public health and safety for everyone, and on the individual level have a direct impact on health outcomes. Poorly designed laws and policies, on the other hand, can fail to achieve the intended results and/or obstruct the realization of fundamental human rights, further disease spread, or cause unintended collateral harms. When done properly, laws can provide the foundation that brings clarity to complexity, embrace nuance, and identifies gaps of uncertainty. However, laws can also shape the societal factors that make disease possible. Law is inseparable from the rest of society, and COVID-19 has exposed just how much laws and policies intersects all facets of society. In the COVID-19 context, evidence-based and well-informed law and policy decisions—made at the right time and in the right place—can and have meant the difference between life or death for many. Having a solid evidentiary base of legal information can promote the understanding of what works well and where, and it can drive resources and action to where they are needed most. We know that legal mechanisms can enable nations to reduce inequities and prepare for emerging threats, like novel pathogens that result in deadly disease outbreaks or antibiotic resistance. The collection and analysis of data on these legal mechanisms is a critical step towards ensuring that legal interventions and legal landscapes are effectively incorporated into more traditional kinds of health science data analyses. The COVID-19 Law Labs see a unique opportunity to collect and analyze this kind of non-traditional data to inform policy using laws and policies from across the globe and across diseases. This global view is critical to assessing the efficacy of policies in a wide range of cultural, economic, and demographic circumstances. The COVID-19 Law Lab is not just a collection of legal texts relating to COVID-19; it is a dataset of concise and actionable legal information that can be used by health researchers, social scientists, academics, human rights advocates, law and policymakers, government decision-makers, and others for cross-disciplinary quantitative and qualitative analysis to identify best practices from this outbreak, and previous ones, to be better prepared for potential future public health events.

Keywords: public health law, surveillance, policy, legal, data

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2819 Urban Roof Farming: A Smart City Solution Leading to Sustainability

Authors: Phibankhamti Ryngnga

Abstract:

It is a common phenomenon worldwide that farmland has been gradually converted for urban development particularly in the 21st century keeping in mind the population increase on the other hand. Since food demand and supply are not in equilibrium in urban set up, therefore, there is a need for alternative to feed the hungry urban settlers worldwide. In this regard, urban rooftop farming is the only way out to meet the growing demand for food production with the extra benefits of making our urban areas and cities greener and when the populace is exposed to nature and vegetation, it in turn provides an array of psychological benefits, from decreased anxiety to increased productivity. Bare roofs in cities absorb and then radiate heat — a phenomenon known as the “heat island effect. This increases energy usage and contributes to the poor air quality that often plagues big cities. But Urban rooftop farming do provide many solutions to help cool buildings, ultimately reducing carbon emissions, and by growing food in the communities they serve, rooftop farmers lessen the environmental impact of food transportation. This paper will emphasise the significance of Urban roof farming in the present century which in itself a multi-solution to various city problems.

Keywords: urban, roof farming, smart solution, sustainability

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