Search results for: peripheral arterial disease
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4223

Search results for: peripheral arterial disease

2603 Assessing Walkability in New Cities around Cairo

Authors: Lobna Ahmed Galal

Abstract:

Modal integration has given minimal consideration in cities of developing countries, as well as the declining dominance of public transport, and predominance of informal transport, the modal share of informal taxis in greater Cairo has increased from 6% in 1987 to 37% in 2001 and this has since risen even higher, informal and non-motorized modes of transport acting as a gap filler by feeding other modes of transport, not by design or choice, but often by lack of accessible and affordable public transport. Yet non-motorized transport is peripheral, with minimal priority in urban planning and investments, lacking of strong polices to support non-motorized transport, for authorities development is associated with technology and motorized transport, and promotion of non-motorized transport may be considered corresponding to development, as well as social stigma against non-motorized transport, as it is seen a travel mode for the poor. Cairo as a city of a developing country, has poor quality infrastructure for non-motorized transport, suffering from absence of dedicated corridors, and when existing they are often encroached for commercial purposes, widening traffic lanes at the expense of sidewalks, absence of footpaths, or being overcrowded, poor lighting, making walking unsafe and yet, lack of financial supply to such facilities as it is often considered beyond city capabilities. This paper will deal with the objective measuring of the built environment relating to walking, in some neighborhoods of new cities around Cairo, In addition to comparing the results of the objective measures of the built environment with the level of self-reported survey. The first paper's objective is to show how the index ‘walkability of community neighborhoods’ works in the contexts in neighborhoods of new cities around Cairo. The procedure of objective measuring is of a high potential to be carried out by using GIS.

Keywords: assessing, built environment, Cairo, walkability

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2602 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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2601 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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2600 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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2599 Role of Teachers in Fostering the Culture of Peace in Higher Education Context: A Literature Review

Authors: Maliheh Rezaei

Abstract:

Peace education has been introduced into many higher educational contexts by designing different programs, expecting to result in constructive changes, specifically in post-conflict countries. Teachers are the potential agents of positive change who play a major role in fostering the culture of peace in their classes. The purpose of this literature review was thus to evaluate the implementation of peace pedagogies by teachers in the context of higher education. More specifically, it addressed a) the role and characteristics of teachers and b) the pedagogies that they used to construct the culture of peace. The systematic literature review was used and several inclusion criteria were applied. Only papers published in English, which contained the keywords of university, higher education, peace, peace education, and similar derivatives such as ‘peacebuilding’ in their title and/or abstract, were included in this review. Moreover, only papers that dealt with the actual implementation of peace education theories were investigated. Findings highlighted that most teachers relied on pedagogies adopted from social justice, global citizenship, and positive psychology practices aiming to foster positive human traits such as resilience, empathy and reflection that were also believed to play an important role in peacebuilding efforts. Nevertheless, the incorporation of peace remained peripheral. The main challenge to incorporate the tenets of peace education was the shortage of teachers who were skilled and qualified enough to incorporate and promote the culture of peace in their classes. This literature review presents the body of research that has linked peace education to Higher Education. Therefore, it informs teachers about the potential roles they have in creating a peaceful and sustainable future. It also presents them with more effective pedagogies and practices to successfully integrate peace-related activities in Higher Education.

Keywords: culture of peace, higher education, teacher, pedogogy

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2598 Role of Transient Receptor Potential Vanilloid 1 in Electroacupuncture Analgesia on Chronic Inflammatory Pain in Mice

Authors: Jun Yang, Ching-Liang Hsieh, Yi-Wen Lin

Abstract:

Chronic inflammatory pain results from peripheral tissue injury or local inflammation to increase the release of protons, histamines, adenosine triphosphate, and several proinflammatory cytokines. Transient receptor potential vanilloid 1 (TRPV1) is involved in fibromyalgia, neuropathic, and inflammatory pain; however, its exact mechanisms in chronic inflammatory pain are still unclear. We investigate the analgesic effect of EA by injecting complete Freund’s adjuvant (CFA) in the hind paw of mice to induce chronic inflammatory pain ( > 14 d). Our results showed that EA significantly reduced chronic mechanical and thermal hyperalgesia in the chronic inflammatory pain model. Chronic mechanical and thermal hyperalgesia was also abolished in TRPV1−/− mice. TRPV1 increased in the dorsal root ganglion (DRG) and spinal cord (SC) at 2 weeks after CFA injection. The expression levels of downstream molecules such as pPKA, pPI3K, and pPKC increased, as did those of pERK, pp38, and pJNK. Transcription factors (pCREB and pNFκB) and nociceptive ion channels (Nav1.7 and Nav1.8) were involved in this process. Inflammatory mediators such as GFAP (Glial fibrillary acidic protein), S100B, and RAGE (Receptor for advanced glycation endproducts) were also involved. The expression levels of these molecules were reduced in EA (electroacupuncture) and TRPV1−/−mice but not in the sham EA group. The present study demonstrated that EA or TRPV1 gene deletion reduced chronic inflammatory pain through TRPV1 and related molecules. In addition, our data provided evidence to support the clinical use of EA for treating chronic inflammatory pain.

Keywords: auricular electric-stimulation, epileptic seizures, anti-inflammation, electroacupuncture

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2597 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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2596 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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2595 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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2594 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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2593 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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2592 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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2591 The First Report of Aberrant Corneal Occlusion in Rabbit in Iran

Authors: Bahador Bardshiri, Omid Moradi, Amir Komeilian, Nima Panahifar

Abstract:

Formation of a conjunctival membrane over the corneal surface is a condition unique to rabbits that has been labeled aberrant corneal occlusion or pseudopterygium. In the summer of 2013, a five years old male Standard Chinchilla rabbit were presented to Karaj Central Veterinary hospital and the owner complained that his rabbit shows degrees of blindness and there were opacities on both eyes of the presented rabbit. Ophthalmic examination of the affected eyes revealed a conjunctival fold stretching over the cornea of both eyes. The fold originated from limbus and it was vascularized and centrally thickened. There were no attachments to the corneal epithelium and the fold could be easily lifted. Surgery was performed under general anesthesia. The conjunctival fold was incised centrifugally up to its attachment at the limbus and the lid margin using small scissors. The central rim of the segment was then replaced to its normal position in the fornix and fixed with mattress sutures (7/0) passing through outside skin. After the surgery, eye drops containing dexamethasone, gentamicin and polymixin were applied twice daily up to 3 weeks. Within the observation period (8 months) no recurrence was noted. "Pseudo" in the term pseudopterygium refers to the fact that the conjunctival membrane is not adhering to the underlying cornea, but growing over it. In rare cases, the membrane may be loosely attached to the cornea, but can be easily separated without causing damage. It can cover only a small part of the cornea with an annular peripheral opacification of the cornea, or cover it almost fully, leading to blindness. Ethiopathogenesis remains unclear and recurrence of the problem is very likely. The surgical technique that used here decreases probability of recurrence of conjunctival fold.

Keywords: rabbit, cornea, aberrant corneal occlusion, pseudopterygium

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2590 Portuguese City Reconstructed from Public Space: The Example of the Requalification of Cacém Central Area

Authors: Rodrigo Coelho

Abstract:

As several authors have pointed out (such as Jordi Borja, or Oriol Bohigas), the necessity to “make center” presents itself not only as a imperative response to deal with the processes of dissolution of peripheral urbanization, as it should be assumed, from the point of view its symbolic and functional meaning, as a key concept to think and act on the enlarged city. The notion of re-centralization (successfully applied in urban periphery recompositions, such as in Barcelona or Lyon), understood from the redefinition of mobility, the strengthening of core functions, and from the creation or consolidation of urban fabrics (always articulated with policies of creation and redevelopment of public spaces), seems to become one of the key strategies over the challenge of making the city on the “city periphery”. The question we want to address in this paper concerns, essentially, the importance of public space in the (re) construction of the contemporary "shapeless city” sectors (which, in general, we associate to urban peripheries). We will seek demonstrate, from the analysis of a Portuguese case study–The Cacém Central Area requalification, integrated in Polis Program (National Program for Urban Rehabilitation and Environmental Improvement of Cities, released in 1999 by the Portuguese government), the conditions under which the public space project can act, subsequently, in the urban areas of recent formation, where, in many situations, the public space did not have a structuring role in its urbanization, seeing its presence reduced to a residual character. More specifically, we intend to demonstrate with this example the methodological and urban design aspects that led to the regeneration of a disqualified and degraded urban area, by intervening consistently and profoundly in public space (with well defined objectives and criteria, and framed in a more comprehensive strategy, attentive to the various scales of urban design).

Keywords: public space, urban design, urban regeneration, urban and regional studies

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2589 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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2588 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

Procedia PDF Downloads 136
2587 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

Procedia PDF Downloads 488
2586 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

Procedia PDF Downloads 141
2585 Associations between Physical Activity and Risk Factors for Type II Diabetes in Prediabetic Adults

Authors: Rukia Yosuf

Abstract:

Diabetes is a national healthcare crisis related to both macrovascular and microvascular complications. We hypothesized that higher levels of physical activity are associated with lower total and visceral fat mass, lower systolic blood pressure, and increased insulin sensitivity. Participant inclusion criteria: 21-50 years old, BMI ≥ 30 kg/m2, hemoglobin A1C 5.7-6.4, fasting glucose 100-125 mg/dL, and HOMA IR ≥ 2.5. Exclusion criteria: history of diabetes, hypertension, HIV, renal disease, hearing loss, alcoholic intake over four drinks daily, use of organic nitrates or PDE5 inhibitors, and decreased cardiac function. Total physical activity was measured using accelerometers, body composition using DXA, and insulin resistance via fsIVGTT. Clinical and biochemical cardiometabolic risk factors, blood pressure and heart rate were obtained using a calibrated sphygmomanometer. Anthropometric measures, fasting glucose, insulin, lipid profile, C-reactive protein, and BMP were analyzed using standard procedures. Within our study, we found correlations between levels of physical activity in a heterogeneous group of prediabetic adults. Patients with more physical activity had a higher degree of insulin sensitivity, lower blood pressure, total visceral adipose tissue, and overall lower total mass. Total physical activity levels showed small, but significant correlations with systolic blood pressure, visceral fat, lean mass and insulin sensitivity. After normalizing for the race, age, and gender using multiple regression, these associations were no longer significant considering our small sample size. More research into prediabetes will decrease the population of diabetics overall. In the future, we could increase sample size and conduct cross sectional and longitudinal studies in various populations with prediabetes.

Keywords: diabetes, kidney disease, nephrology, prediabetes

Procedia PDF Downloads 187
2584 Russia’s Role in Resolving the Nagorno-Karabakh Conflict 1990-2020

Authors: Friba Haidari

Abstract:

The aim of the study is to identify Russia's role in managing the Nagorno-Karabakh conflict betweenArmenia and Azerbaijan during the years 1990 to 2020. The Nagorno-Karabakh crisis can not be considered a mere territorial conflict but also a crossroads of interests of foreign actors. Geopolitical rivalries and the access to energy by regional and trans-regional actors have complicated the crisis and created a security challenge in the region, which is likely to escalate into a full-blown war between the parties involved. The geopolitical situation of Nagorno-Karabakh and its current situation have affected all peripheral states in some way. Russia, as one of the main actors in this scene, has been actively involved since the beginning of the crisis. The Russians have always sought to strengthen their influence and presence in the Nagorno-Karabakh crisis. Russia's efforts to weaken the role of the Minsk Group, The presence of Western actors, and the deployment of Russian forces in the disputed area can be assessed in this context. However, this study seeks to answer the question of what role did Russia play in managing the Nagorno-Karabakh conflict between Armenia and Azerbaijan between 1990 and 2020? The study hypothesizes that Russia has prevented the escalation of the Nagorno-Karabakh conflict through mediation and some coercion. This study is divided into four parts, including conflict management as a theoretical framework; Examining the competition and the role of actors in the Caucasus region, especially the role of the Minsk Group, and what approach or tools and methods Russia has used in its foreign policy in managing the conflict, and finally what are the relations between the countries involved and what will be Russia's role in the future? Was discussed. This study examines the analysis and transfer of ideas and information using authoritative international sources with an explanatory method and shares its results with everyone.

Keywords: Russia, conflict, nagorno-karabakh, management

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2583 Collagen Deposition in Lung Parenchyma Driven by Depletion of LYVE-1+ Macrophages Protects Emphysema and Loss of Airway Function

Authors: Yinebeb Mezgebu Dagnachew, Hwee Ying Lim, Liao Wupeng, Sheau Yng Lim, Lim Sheng Jie Natalie, Veronique Angeli

Abstract:

Collagen is essential for maintaining lung structure and function, and its remodeling has been associated with respiratory diseases, including chronic obstructive pulmonary disease (COPD). However, the cellular mechanisms driving collagen remodeling and the functional implications of this process in the pathophysiology of pulmonary diseases remain poorly understood. Using a mouse model of Lyve-1 expressing macrophage depletion, we found that the absence of this subpopulation of tissue-resident macrophage led to the preferential deposition of type I collagen fibers around the alveoli and bronchi in the steady state. Further analysis by polarized light microscopy revealed that the collagen fibers accumulating in the lungs depleted of Lyve-1+ macrophages were thicker and crosslinked. A decrease in MMP-9 gene expression and proteolytic activity, together with an increase in Col1a1, Timp-3 and Lox gene expression, accompanied the collagen alterations. Next, we investigated the effect of the collagen remodeling on the pathophysiology of COPD and airway function in mouse lacking Lyve-1+ macrophage exposed chronically to cigarette smoke (CS), a well-established animal model of COPD. We showed that the deposition of collagen protected mouse against the destruction of alveoli (emphysema) and bronchi thickening after CS exposure and prevented loss of airway function. Thus, we demonstrate that interstitial Lyve-1+ macrophages regulate the composition, amount, and architecture of the collagen network in the lungs and that such collagen remodeling functionally impacts the development of COPD. This study further supports the potential of targeting collagen as a promising approach to treating respiratory diseases.

Keywords: lung, extracellular matrix, chronic obstructive pulmonary disease, matrix metalloproteinases, collagen

Procedia PDF Downloads 37
2582 An Educational Program Based on Health Belief Model to Prevent Non-Alcoholic Fatty Liver Disease among Iranian Women

Authors: Babak Nemat

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, and 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: non-alcoholic fatty liver, health belief model, education, women

Procedia PDF Downloads 61
2581 Genetic Variation in CYP4F2 and VKORC1: Pharmacogenomics Implications for Response to Warfarin

Authors: Zinhle Cindi, Collet Dandara, Mpiko Ntsekhe, Edson Makambwa, Miguel Larceda

Abstract:

Background: Warfarin is the most commonly used drug in the management of thromboembolic disease. However, there is a huge variability in the time, number of doses or starting doses for patients to achieve the required international normalised ratio (INR) which is compounded by a narrow therapeutic index. Many genetic-association studies have reported on European and Asian populations which have led to the designing of specific algorithms that are now being used to assist in warfarin dosing. However, very few or no studies have looked at the pharmacogenetics of warfarin in African populations, yet, huge differences in dosage requirements to reach the same INR have been observed. Objective: We set out to investigate the distribution of 3 SNPs CYP4F2 c.1347C > T, VKORC1 g.-1639G > A and VKORC1 c.1173C > T among South African Mixed Ancestry (MA) and Black African patients. Methods: DNA was extracted from 383 participants and subsequently genotyped using PCR/RFLP for the CYP4F2 c.1347 (V433M) (rs2108622), VKORC1 g.-1639 (rs9923231) and VKORC1 c.1173 (rs9934438) SNPs. Results: Comparing the Black and MA groups, significant differences were observed in the distribution of the following genotypes; CYP4F2 c.1347C/T (23% vs. 39% p=0.03). All VKORC1 g.-1639G > A genotypes (p < 0.006) and all VKORC1 c.1173C > T genotypes (p < 0.007). Conclusion: CYP4F2 c.1347T (V433M) reduces CYP4F2 protein levels and therefore expected to affect the amount of warfarin needed to block vitamin k recycling. The VKORC1 g-1639A variant alters transcriptional regulation therefore affecting the function of vitamin k epoxide reductase in vitamin k production. The VKORC1 c.1173T variant reduces the enzyme activity of VKORC1 consequently enhancing the effectiveness of warfarin. These are preliminary results; more genetic characterization is required to understand all the genetic determinants affecting how patients respond to warfarin.

Keywords: algorithms, pharmacogenetics, thromboembolic disease, warfarin

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2580 Evaluation of Some Serum Proteins as Markers for Myeloma Bone Disease

Authors: V. T. Gerov, D. I. Gerova, I. D. Micheva, N. F. Nazifova-Tasinova, M. N. Nikolova, M. G. Pasheva, B. T. Galunska

Abstract:

Multiple myeloma (MM) is the most frequent plasma cell (PC) dyscrasia that involves the skeleton. Myeloma bone disease (MBD) is characterized by osteolytic bone lesions as a result of increased osteoclasts activity not followed by reactive bone formation due to osteoblasts suppression. Skeletal complications cause significant adverse effects on quality of life and lead to increased morbidity and mortality. Last decade studies revealed the implication of different proteins in osteoclast activation and osteoblast inhibition. The aim of the present study was to determine serum levels of periostin, sRANKL and osteopontin and to evaluate their role as bone markers in MBD. Materials and methods. Thirty-two newly diagnosed MM patients (mean age: 62.2 ± 10.7 years) and 33 healthy controls (mean age: 58.9 ± 7.5 years) were enrolled in the study. According to IMWG criteria 28 patients were with symptomatic MM and 4 with monoclonal gammopathy of undetermined significance (MGUS). In respect to their bone involvement all symptomatic patients were divided into two groups (G): 9 patients with 0-3 osteolytic lesions (G1) and 19 patients with >3 osteolytic lesions and/or pathologic fractures (G2). Blood samples were drawn for routine laboratory analysis and for measurement of periostin, sRANKL and osteopontin serum levels by ELISA kits (Shanghai Sunred Biological Technology, China). Descriptive analysis, Mann-Whitney test for assessment the differences between groups and non-parametric correlation analysis were performed using GraphPad Prism v8.01. Results. The median serum levels of periostin, sRANKL and osteopontin of ММ patients were significantly higher compared to controls (554.7pg/ml (IQR=424.0-720.6) vs 396.9pg/ml (IQR=308.6-471.9), p=0.0001; 8.9pg/ml (IQR=7.1-10.5) vs 5.6pg/ml (IQR=5.1-6.4, p<0.0001 and 514.0ng/ml (IQR=469.3-754.0) vs 387.0ng/ml (IQR=335.9-441.9), p<0.0001, respectively). for assessment of differences between groups and non-parametric correlation analysis were performed using GraphPad Prism v8.01. Statistical significance was found for all tested bone markers between symptomatic MM patients and controls: G1 vs controls (p<0.03), G2 vs controls (p<0.0001) for periostin; G1 vs controls (p<0.0001), G2 vs controls (p<0.0001) for sRANKL; G1 vs controls (p=0.002), G2 vs controls (p<0.0001) for osteopontin, as well between symptomatic MM patients and MGUS patients: G1 vs MGUS (p<0.003), G2 vs MGUS (p=0.003) for periostin; G1 vs MGUS (p<0.05), G2 vs MGUS (p<0.001) for sRANKL; G1 vs MGUS (p=0.011), G2 vs MGUS (p=0.0001) for osteopontin. No differences were detected between MGUS and controls and between patients in G1 and G2 groups. Spearman correlation analysis revealed moderate positive correlation between periostin and beta-2-microglobulin (r=0.416, p=0.018), percentage bone marrow myeloma PC (r=0.432, p=0.014), and serum total protein (r=0.427, p=0.015). Osteopontin levels were also positively related to beta-2-microglobulin (r=0.540, p=0.0014), percentage bone marrow myeloma PC (r=0.423, p=0.016), and serum total protein (r=0.413, p=0.019). Serum sRANKL was only related to beta-2-microglobulin levels (r=0.398, p=0.024). Conclusion: In the present study, serum levels of periostin, sRANKL and osteopontin in newly diagnosed MM patients were evaluated. They gradually increased from MGUS to more advanced stages of MM reflecting the severity of bone destruction. These results support the idea that some new protein markers could be used in monitoring the MBD as a most severe complication of MM.

Keywords: myeloma bone disease, periostin, sRANKL, osteopontin

Procedia PDF Downloads 57
2579 Leveraging Remote Assessments and Central Raters to Optimize Data Quality in Rare Neurodevelopmental Disorders Clinical Trials

Authors: Pamela Ventola, Laurel Bales, Sara Florczyk

Abstract:

Background: Fully remote or hybrid administration of clinical outcome measures in rare neurodevelopmental disorders trials is increasing due to the ongoing pandemic and recognition that remote assessments reduce the burden on families. Many assessments in rare neurodevelopmental disorders trials are complex; however, remote/hybrid trials readily allow for the use of centralized raters to administer and score the scales. The use of centralized raters has many benefits, including reducing site burden; however, a specific impact on data quality has not yet been determined. Purpose: The current study has two aims: a) evaluate differences in data quality between administration of a standardized clinical interview completed by centralized raters compared to those completed by site raters and b) evaluate improvement in accuracy of scoring standardized developmental assessments when scored centrally compared to when scored by site raters. Methods: For aim 1, the Vineland-3, a widely used measure of adaptive functioning, was administered by site raters (n= 52) participating in one of four rare disease trials. The measure was also administered as part of two additional trials that utilized central raters (n=7). Each rater completed a comprehensive training program on the assessment. Following completion of the training, each clinician completed a Vineland-3 with a mock caregiver. Administrations were recorded and reviewed by a neuropsychologist for administration and scoring accuracy. Raters were able to certify for the trials after demonstrating an accurate administration of the scale. For site raters, 25% of each rater’s in-study administrations were reviewed by a neuropsychologist for accuracy of administration and scoring. For central raters, the first two administrations and every 10th administration were reviewed. Aim 2 evaluated the added benefit of centralized scoring on the accuracy of scoring of the Bayley-3, a comprehensive developmental assessment widely used in rare neurodevelopmental disorders trials. Bayley-3 administrations across four rare disease trials were centrally scored. For all administrations, the site rater who administered the Bayley-3 scored the scale, and a centralized rater reviewed the video recordings of the administrations and also scored the scales to confirm accuracy. Results: For aim 1, site raters completed 138 Vineland-3 administrations. Of the138 administrations, 53 administrations were reviewed by a neuropsychologist. Four of the administrations had errors that compromised the validity of the assessment. The central raters completed 180 Vineland-3 administrations, 38 administrations were reviewed, and none had significant errors. For aim 2, 68 administrations of the Bayley-3 were reviewed and scored by both a site rater and a centralized rater. Of these administrations, 25 had errors in scoring that were corrected by the central rater. Conclusion: In rare neurodevelopmental disorders trials, sample sizes are often small, so data quality is critical. The use of central raters inherently decreases site burden, but it also decreases rater variance, as illustrated by the small team of central raters (n=7) needed to conduct all of the assessments (n=180) in these trials compared to the number of site raters (n=53) required for even fewer assessments (n=138). In addition, the use of central raters dramatically improves the quality of scoring the assessments.

Keywords: neurodevelopmental disorders, clinical trials, rare disease, central raters, remote trials, decentralized trials

Procedia PDF Downloads 172
2578 Implementing 3D Printing for 3D Digital Modeling in the Classroom

Authors: Saritdikhun Somasa

Abstract:

3D printing fabrication has empowered many artists in many fields. Artists who work in stop motion, 3D modeling, toy design, product design, sculpture, and fine arts become one-stop shop operations–where they can design, prototype, and distribute their designs for commercial or fine art purposes. The author has developed a digital sculpting course that fosters digital software, peripheral hardware, and 3D printing with traditional sculpting concept techniques to address the complexities of this multifaceted process, allowing the students to produce complex 3d-printed work. The author will detail the preparation and planning for pre- to post-process 3D printing elements, including software, materials, space, equipment, tools, and schedule consideration for small to medium figurine design statues in a semester-long class. In addition, the author provides insight into teaching challenges in the non-studio space that requires students to work intensively on post-printed models to assemble parts, finish, and refine the 3D printed surface. Even though this paper focuses on the 3D printing processes and techniques for small to medium design statue projects for the Digital Media program, the author hopes the paper will benefit other fields of study such as craft practices, product design, and fine-arts programs. Other schools that might implement 3D printing and fabrication in their programs will find helpful information in this paper, such as a teaching plan, choices of equipment and materials, adaptation for non-studio spaces, and putting together a complete and well-resolved project for students.

Keywords: 3D digital modeling, 3D digital sculpting, 3D modeling, 3D printing, 3D digital fabrication

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2577 Analysis of ZBTB17 Gene rs10927875 Polymorphism in Relation to Dilated Cardiomyopathy in Slovak Population

Authors: I. Boroňová, J. Bernasovská, J. Kmec, E. Petrejčíková

Abstract:

Dilated cardiomyopathy (DCM) is a primary myocardial disease, it is characterized by progressive systolic dysfunction due to cardiac chamber dilatation and inefficient myocardial contractility with estimated prevalence of 37 in 100 000 people. It is the most frequent cause of heart failure and cardiac transplantation in young adults. About one-third of all patients have a suspected familial disease indicating a genetic basis of DCM. Many candidate gene studies in humans have tested the association of single nucleotide polymorphisms (SNPs) in various genes coding for proteins with a known cardiovascular function. In our study we present the results of ZBTB17 gene rs10927875 polymorphism genotyping in relation to dilated cardiomyopathy in Slovak population. The study included 78 individuals, 39 patients with DCM and 39 healthy control persons. The mean age of patients with DCM was 50.7±11.5 years; the mean age of individuals in control group was 51.3±9.8 years. Risk factors detected at baseline in each group included age, sex, body mass index, smoking status, diabetes and blood pressure. Genomic DNA was extracted from leukocytes by a standard methodology and screened for rs10927875 polymorphism in intron of ZBTB17 gene using Real-time PCR method (Step One Applied Biosystems). The distribution of investigated genotypes for rs10927875 polymorphism in the group of patients with DCM was as follows: CC (89.74%), CT (10.26%), TT (0%), and the distribution in the control group: CC (92.31%), CT (5.13%), and TT (2.56%). Using the chi-square (χ2) test we compared genotype and allele frequencies between patients and controls. There was no difference in genotype or allele frequencies in ZBTB17 gene rs10927875 polymorphism between patients and control group (χ2=3.028, p=0.220; χ2=0.264, p=0.608). Our results represent an initial study, it can be considered as preliminary and first of its kind in Slovak population. Further studies of ZBTB17 gene polymorphisms of more numerous files and additional functional investigations are needed to fully understand the role of genetic associations.

Keywords: dilated cardiomyopathy, SNP polymorphism, ZBTB17 gene, bioscience

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2576 Whole Exome Sequencing Data Analysis of Rare Diseases: Non-Coding Variants and Copy Number Variations

Authors: S. Fahiminiya, J. Nadaf, F. Rauch, L. Jerome-Majewska, J. Majewski

Abstract:

Background: Sequencing of protein coding regions of human genome (Whole Exome Sequencing; WES), has demonstrated a great success in the identification of causal mutations for several rare genetic disorders in human. Generally, most of WES studies have focused on rare variants in coding exons and splicing-sites where missense substitutions lead to the alternation of protein product. Although focusing on this category of variants has revealed the mystery behind many inherited genetic diseases in recent years, a subset of them remained still inconclusive. Here, we present the result of our WES studies where analyzing only rare variants in coding regions was not conclusive but further investigation revealed the involvement of non-coding variants and copy number variations (CNV) in etiology of the diseases. Methods: Whole exome sequencing was performed using our standard protocols at Genome Quebec Innovation Center, Montreal, Canada. All bioinformatics analyses were done using in-house WES pipeline. Results: To date, we successfully identified several disease causing mutations within gene coding regions (e.g. SCARF2: Van den Ende-Gupta syndrome and SNAP29: 22q11.2 deletion syndrome) by using WES. In addition, we showed that variants in non-coding regions and CNV have also important value and should not be ignored and/or filtered out along the way of bioinformatics analysis on WES data. For instance, in patients with osteogenesis imperfecta type V and in patients with glucocorticoid deficiency, we identified variants in 5'UTR, resulting in the production of longer or truncating non-functional proteins. Furthermore, CNVs were identified as the main cause of the diseases in patients with metaphyseal dysplasia with maxillary hypoplasia and brachydactyly and in patients with osteogenesis imperfecta type VII. Conclusions: Our study highlights the importance of considering non-coding variants and CNVs during interpretation of WES data, as they can be the only cause of disease under investigation.

Keywords: whole exome sequencing data, non-coding variants, copy number variations, rare diseases

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2575 The Effect of High Intensity by Intervals Training on Plasma Interleukin 13 and Insulin Resistance in Patients with Attention Deficit Hyperactivity Disorder (ADHD)

Authors: Goodarzvand Fatemeh, Soori Rahman, Effatpanah Mohammad, Ajbarnejad Ali

Abstract:

Attention deficit hyperactivity disorder (ADHD) is characterized by a pervasive pattern of developmentally inappropriate inattentive, impulsive and hyperactive behaviors that typically begin during the preschool ages and often persist into adulthood. This disorder is related to autism and schizophrenia and other psychological disorders and clinical conditions such as insulin resistance and they may operate through common pathways, and treatments used exclusively for one of these conditions may prove beneficial for the others. While ADHD is not fully understood as developmental disorder with an etiopathogeny, but studies show that core symptom of disorder was associated with and increased by the interleukins IL-13, where relation of IL-13 with inattention was notable. Regular exercise improves functions associated with attention deficit hyperactivity disorder (ADHD). However, the impact of exercise on cytokines associated with the disease activity remains relatively unexplored. The aim of this study was to examine the effects of 6 weeks high intensity by intervals training (HIIT) on IL-13 levels and insulin resistance in boys with ADHD. Twenty eight boys with ADHD disease in a range of 12-18 year of old participated in this study as the subject. Subjects were divided into control group (n=10) and training group (n=18) randomly. The training group performed progressive HIIT program, 3 days a week for 6 weeks. The control group was in absolute rest at the same time. The results showed that after six weeks of HIIT, IL-13 decreased in the exercise group and these changes achieved (p= 0.002) statistical significance (p < 0.005). The results suggest HIIT with specific intensity and duration utilized in this study had not significant effect on insulin resistance levels in female patients with ADHD (p=0.39), while the difference in the average control and case group was decreased.

Keywords: attention deficit hyperactivity disorder, interleukin 13, insulin resistance, high intensity by intervals training

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2574 Occupational Exposure to Electromagnetic Fields Can Increase the Release of Mercury from Dental Amalgam Fillings

Authors: Ghazal Mortazavi, S. M. J. Mortazavi

Abstract:

Electricians, power line engineers and power station workers, welders, aluminum reduction workers, MRI operators and railway workers are occupationally exposed to different levels of electromagnetic fields. Mercury is among the most toxic metals. Dental amalgam fillings cause significant exposure to elemental mercury vapour in the general population. Today, substantial evidence indicates that mercury even at low doses may lead to toxicity. Increased release of mercury from dental amalgam fillings after exposure to MRI or microwave radiation emitted by mobile phones has been previously shown by our team. Moreover, our recent studies on the effects of stronger magnetic fields entirely confirmed our previous findings. From the other point of view, we have also shown that papers which reported no increased release of mercury after MRI, may have some methodological flaws. Over the past several years, our lab has focused on the health effects of exposure of laboratory animals and humans to different sources of electromagnetic fields such as mobile phones and their base stations, mobile phone jammers, laptop computers, radars, dentistry cavitrons, and MRI. As a strong association between exposure to electromagnetic fields and mercury level has been found in our studies, our findings lead us to this conclusion that occupational exposure to electromagnetic fields in workers with dental amalgam fillings can lead to elevated levels of mercury. Studies which reported that exposure to mercury can be a risk factor of Alzheimer’s disease (AD) due to the accumulation of amyloid beta protein (Aβ) in the brain and those reported that long-term occupational exposure to high levels of electromagnetic fields can increase the risk of Alzheimer's disease and dementia in male workers support our concept and confirm the significant role of the occupational exposure to electromagnetic fields in increasing the mercury level in workers with amalgam fillings.

Keywords: occupational exposure, electromagnetic fields, workers, mercury release, dental amalgam, restorative dentistry

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