Search results for: vascular dementia
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 511

Search results for: vascular dementia

331 The Effects of Ellagic Acid on Rat Lungs Induced Tobacco Smoke

Authors: Nalan Kaya, Gonca Ozan, Elif Erdem, Neriman Colakoglu, Enver Ozan

Abstract:

The toxic effects of tobacco smoke exposure have been detected in numerous studies. Ellagic acid (EA), (2,3,7,8-tetrahydroxy [1]-benzopyranol [5,4,3-cde] benzopyran 5,10-dione), a natural phenolic lactone compound, is found in various plant species including pomegranate, grape, strawberries, blackberries and raspberries. Similar to the other effective antioxidants, EA can safely interact with the free radicals and reduces oxidative stress through the phenolic ring and hydroxyl components in its structure. The aim of the present study was to examine the protective effects of ellagic acid against oxidative damage on lung tissues of rats induced by tobacco smoke. Twenty-four male adult (8 weeks old) Spraque-Dawley rats were divided randomly into 4 equal groups: group I (Control), group II (Tobacco smoke), group III (Tobacco smoke + corn oil) and group IV (Tobacco smoke + ellagic acid). The rats in group II, III and IV, were exposed to tobacco smoke 1 hour twice a day for 12 weeks. In addition to tobacco smoke exposure, 12 mg/kg ellagic acid (dissolved in corn oil), was applied to the rats in group IV by oral gavage. Equal amount of corn oil used in solving ellagic acid was applied to the rats by oral gavage in group III. At the end of the experimental period, rats were decapitated. Lung tissues and blood samples were taken. The lung slides were stained by H&E and Masson’s Trichrome methods. Also, galactin-3 stain was applied. Biochemical analyzes were performed. Vascular congestion and inflammatory cell infiltration in pulmonary interstitium, thickness in interalveolar septum, cytoplasmic vacuolation in some macrophages and galactin-3 positive cells were observed in histological examination of tobacco smoke group. In addition to these findings, hemorrhage in pulmonary interstitium and bronchial lumen was detected in tobacco smoke + corn oil group. Reduced vascular congestion and hemorrhage in pulmoner interstitium and rarely thickness in interalveolar septum were shown in tobacco smoke + EA group. Compared to group-I, group-II GSH level was decreased and MDA level was increased significantly. Nevertheless group-IV GSH level was higher and MDA level was lower than group-II. The results indicate that ellagic acid could protect the lung tissue from the tobacco smoke harmful effects.

Keywords: ellagic acid, lung, rat, tobacco smoke

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330 Angiopermissive Foamed and Fibrillar Scaffolds for Vascular Graft Applications

Authors: Deon Bezuidenhout

Abstract:

Pre-seeding with autologous endothelial cells improves the long-term patency of synthetic vascular grafts levels obtained with autografts, but is limited to a single centre due to resource, time and other constraints. Spontaneous in vivo endothelialization would obviate the need for pre-seeding, but has been shown to be absent in man due to limited transanastomotic and fallout healing, and the lack of transmural ingrowth due to insufficient porosity. Two types of graft scaffolds with increased interconnected porosity for improved tissue ingrowth and healing are thus proposed and described. Foam-type polyurethane (PU) scaffolds with small, medium and large, interconnected pores were made by phase inversion and spherical porogen extraction, with and without additional surface modification with covalently attached heparin and subsequent loading with and delivery of growth factors. Fibrillar scaffolds were made either by standard electrospinning using degradable PU (Degrapol®), or by dual electrospinning using non-degradable PU. The latter process involves sacrificial fibres that are co-spun with structural fibres and subsequently removed to increased porosity and pore size. Degrapol samples were subjected to in vitro degradation, and all scaffold types were evaluated in vivo for tissue ingrowth and vascularization using rat subcutaneous model. The foam scaffolds were additionally evaluated in a circulatory (rat infrarenal aortic interposition) model that allows for the grafts to be anastomotically and/or ablumenally isolated to discern and determine endothelialization mode. Foam-type grafts with large (150 µm) pores showed improved subcutaneous healing in terms of vascularization and inflammatory response over smaller pore sizes (60 and 90µm), and vascularization of the large porosity scaffolds was significantly increased by more than 70% by heparin modification alone, and by 150% to 400% when combined with growth factors. In the circulatory model, extensive transmural endothelialization (95±10% at 12 w) was achieved. Fallout healing was shown to be sporadic and limited in groups that were ablumenally isolated to prevent transmural ingrowth (16±30% wrapped vs. 80±20% control; p<0.002). Heparinization and GF delivery improved both mural vascularization and lumenal endothelialization. Degrapol electrospun scaffolds showed decrease in molecular mass and corresponding tensile strength over the first 2 weeks, but very little decrease in mass over the 4w test period. Studies on the effect of tissue ingrowth with and without concomitant degradation of the scaffolds, are being used to develop material models for the finite element modelling. In the case of the dual-spun scaffolds, the PU fibre fraction could be controlled shown to vary linearly with porosity (P = −0.18FF +93.5, r2=0.91), which in turn showed inverse linear correlation with tensile strength and elastic modulus (r2 > 0.96). Calculated compliance and burst pressures of the scaffolds increased with fibre fraction, and compliances matching the human popliteal artery (5-10 %/100 mmHg), and high burst pressures (> 2000 mmHg) could be achieved. Increasing porosity (76 to 82 and 90%) resulted in increased tissue ingrowth from 33±7 to 77±20 and 98±1% after 28d. Transmural endothelialization of highly porous foamed grafts is achievable in a circulatory model, and the enhancement of porosity and tissue ingrowth may hold the key the development of spontaneously endothelializing electrospun grafts.

Keywords: electrospinning, endothelialization, porosity, scaffold, vascular graft

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

Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Kawasaki disease (KD) is the primary cause of acquired pediatric heart disease as an acute vasculitis. In children with prolonged fever, rash, and inflammation of the mucosa KD must be considered as a clinical diagnosis. There is a persuasive suggestion of immune-mediated damage as the pathophysiologic cascade of KD. For example, the invasion of cytotoxic T-cells supports a viral etiology and the inflammasome of the innate immune system is a critical component in the vasculitis formation in KD. Animal models of KD propose the cytokine profiles, such as increased IL-1 and GM-CSF, which cause vascular damage. CRP and IFN-γ elevated expression and the upregulation of IL-6, and IL-10 production are also described in previous studies. Untreated KD is a critical risk factor for coronary artery diseases and myocardial infarction. Vascular damage may encompass amplified T-cell activity. SMAD3 is an essential molecule in down-regulating T-cells and increasing expression of FoxP3. It has a critical effect in the differentiation of regulatory T-cells. The discrepancy of regulatory T-cells and pro-inflammatory Th17 has been studied in acute coronary syndrome during KD. However in the coronary artery damaged lymphocytes and IgA plasma cells are seen at the lesion locations, the major immune cells in the coronary lesions are monocytes/macrophages and neutrophils. These cells secrete TNF-α, and activates matrix metalloprotease (MMP)-9, reducing the integrity of vessels and prompting patients to arise aneurysm. MMPs can break down the components of the extracellular matrix and assist immune cell movement. IVIG as an effective form of treatment clarified the role of the immune system, which may target pathogenic antigens and regulate cytokine production. Several reports have revealed that in the coronary arteries, high expression of MMP-9 in monocyte/macrophage results in pathologic cascades. Curcumin is a potent antioxidant and anti-inflammatory molecule. Curcumin decreases the production of reactive oxygen and nitrogen species and inhibits transcription factors like AP-1 and NF-κB. Curcumin also contains the characteristics of inhibitory effects on MMPs, especially MMP-9. The upregulation of MMP-9 is an important cellular response. Curcumin treatment caused a reverse effect and down-regulates MMP-9 gene expression which may fund the anti-inflammatory effect. Curcumin inhibits MMP-9 expression via PKC and AMPK-dependent pathways in Human monocytes cells. Elevated expression and activity of MMP-9 are correlated with advanced vascular lesions. AMPK controls lipid metabolism and oxidation, and protein synthesis. AMPK is also necessary for the MMP-9 activity and THP-1 cell adhesion to endothelial cells. Curcumin was shown to inhibit the activation of AMPKα. Compound C (AMPK inhibitor) inhibits MMP-9 expression level. Therefore, through inactivating AMPKs and PKC, curcumin decreases the MMP-9 level, which results in inhibiting monocyte/macrophage differentiation. Compound C also suppress the phosphorylation of three major classes of MAP kinase signaling, suggesting that curcumin may suppress MMP-9 level by inactivation of MAPK pathways. MAPK cascades are activated to induce the expression of MMP-9. Curcumin inhibits MAPKs phosphorylation, which contributes to the down-regulation of MMP-9. This study demonstrated that the potential inhibitory properties of curcumin over MMP-9 lead to a therapeutic strategy to reduce the risk of coronary artery involvement during KD.

Keywords: MMP-9, coronary artery aneurysm, Kawasaki’s disease, curcumin, AMPK, immune system, NF-κB, MAPK

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328 Considerations for the Use of High Intensity Interval Training in Secondary Physical Education

Authors: Amy Stringer, Resa Chandler

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High Intensity Interval Training (HIIT) involves a 3-10-minute circuit of various exercises which is a viable alternative to a traditional cardiovascular and strength training regimen. Research suggests that measures of health-related fitness can either be maintained or actually improve with the use of this training method. After conducting a 6-week HIIT research study with 10-14 year old children, considerations for using a daily HIIT workout are presented. Is the use of HIIT with children a reasonable consideration for physical education programs? The benefits and challenges of this type of an intervention are identified. This study is significant in that achieving fitness gains in a small amount of daily class time is an attractive concept – especially for physical education teachers who often do not have the time necessary to accomplish all of their curricular goals in the amount of class time assigned. Basic methodologies include students participating in a circuit of exercises for 7-10 minutes at 80-95% of max heart rate as measured by heart rate monitors. Student pre and post fitness test data were collected for cardio-vascular endurance, muscular endurance, and body composition. Research notes as well as commentary by the teachers and researchers who participated in the HIIT study contributed to the understanding of the cost-benefit analysis. Major findings of the study are that HIIT has limited effectiveness but is a good choice for limited class times. Student efficacy of their ability to complete the exercises and visible heart rate data were considered to be significant factors in success of the HIIT study. The effective use of technology promoting positive audience effect during the display of heart rate data was more important at the beginning of the study than at the end. Student ‘buy-in’ and motivation, teacher motivation and ‘buy-in’, the variety of activities in the circuit and the fitness level of the student at the beginning of the study were also findings influencing the fitness outcomes of the study. Concluding Statement: High intensity interval training can be used effectively in a secondary physical education program. It is not a ‘magic bullet’ to produce health-related fitness outcomes in every student but it is an effective tool to enhance student fitness in a limited time and contribute to the goals of the program.

Keywords: cardio vascular fitness, children, high intensity interval training, physical education

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327 Best Practice for Post-Operative Surgical Site Infection Prevention

Authors: Scott Cavinder

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Surgical site infections (SSI) are a known complication to any surgical procedure and are one of the most common nosocomial infections. Globally it is estimated 300 million surgical procedures take place annually, with an incidence of SSI’s estimated to be 11 of 100 surgical patients developing an infection within 30 days after surgery. The specific purpose of the project is to address the PICOT (Problem, Intervention, Comparison, Outcome, Time) question: In patients who have undergone cardiothoracic or vascular surgery (P), does implementation of a post-operative care bundle based on current EBP (I) as compared to current clinical agency practice standards (C) result in a decrease of SSI (O) over a 12-week period (T)? Synthesis of Supporting Evidence: A literature search of five databases, including citation chasing, was performed, which yielded fourteen pieces of evidence ranging from high to good quality. Four common themes were identified for the prevention of SSI’s including use and removal of surgical dressings; use of topical antibiotics and antiseptics; implementation of evidence-based care bundles, and implementation of surveillance through auditing and feedback. The Iowa Model was selected as the framework to help guide this project as it is a multiphase change process which encourages clinicians to recognize opportunities for improvement in healthcare practice. Practice/Implementation: The process for this project will include recruiting postsurgical participants who have undergone cardiovascular or thoracic surgery prior to discharge at a Northwest Indiana Hospital. The patients will receive education, verbal instruction, and return demonstration. The patients will be followed for 12 weeks, and wounds assessed utilizing the National Healthcare Safety Network//Centers for Disease Control (NHSN/CDC) assessment tool and compared to the SSI rate of 2021. Key stakeholders will include two cardiovascular surgeons, four physician assistants, two advance practice nurses, medical assistant and patients. Method of Evaluation: Chi Square analysis will be utilized to establish statistical significance and similarities between the two groups. Main Results/Outcomes: The proposed outcome is the prevention of SSIs in the post-op cardiothoracic and vascular patient. Implication/Recommendation(s): Implementation of standardized post operative care bundles in the prevention of SSI in cardiovascular and thoracic surgical patients.

Keywords: cardiovascular, evidence based practice, infection, post-operative, prevention, thoracic, surgery

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326 3 Dimensional (3D) Assesment of Hippocampus in Alzheimer’s Disease

Authors: Mehmet Bulent Ozdemir, Sultan Çagirici, Sahika Pinar Akyer, Fikri Turk

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Neuroanatomical appearance can be correlated with clinical or other characteristics of illness. With the introduction of diagnostic imaging machines, producing 3D images of anatomic structures, calculating the correlation between subjects and pattern of the structures have become possible. The aim of this study is to examine the 3D structure of hippocampus in cases with Alzheimer disease in different dementia severity. For this purpose, 62 female and 38 male- 68 patients’s (age range between 52 and 88) MR scanning were imported to the computer. 3D model of each right and left hippocampus were developed by a computer aided propramme-Surf Driver 3.5. Every reconstruction was taken by the same investigator. There were different apperance of hippocampus from normal to abnormal. In conclusion, These results might improve the understanding of the correlation between the morphological changes in hippocampus and clinical staging in Alzheimer disease.

Keywords: Alzheimer disease, hippocampus, computer-assisted anatomy, 3D

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325 The Effects of Circadian Rhythms Change in High Latitudes

Authors: Ekaterina Zvorykina

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Nowadays, Arctic and Antarctic regions are distinguished to be one of the most important strategic resources for global development. Nonetheless, living conditions in Arctic regions still demand certain improvements. As soon as the region is rarely populated, one of the main points of interest is health accommodation of the people, who migrate to Arctic region for permanent and shift work. At Arctic and Antarctic latitudes, personnel face polar day and polar night conditions during the time of the year. It means that they are deprived of natural sunlight in winter season and have continuous daylight in summer. Firstly, the change in light intensity during 24-hours period due to migration affects circadian rhythms. Moreover, the controlled artificial light in winter is also an issue. The results of the recent studies on night shift medical professionals, who were exposed to permanent artificial light, have already demonstrated higher risks in cancer, depression, Alzheimer disease. Moreover, people exposed to frequent time zones change are also subjected to higher risks of heart attack and cancer. Thus, our main goals are to understand how high latitude work and living conditions can affect human health and how it can be prevented. In our study, we analyze molecular and cellular factors, which play important role in circadian rhythm change and distinguish main risk groups in people, migrating to high latitudes. The main well-studied index of circadian timing is melatonin or its metabolite 6-sulfatoxymelatonin. In low light intensity melatonin synthesis is disturbed and as a result human organism requires more time for sleep, which is still disregarded when it comes to working time organization. Lack of melatonin also causes shortage in serotonin production, which leads to higher depression risk. Melatonin is also known to inhibit oncogenes and increase apoptosis level in cells, the main factors for tumor growth, as well as circadian clock genes (for example Per2). Thus, people who work in high latitudes can be distinguished as a risk group for cancer diseases and demand more attention. Clock/Clock genes, known to be one of the main circadian clock regulators, decrease sensitivity of hypothalamus to estrogen and decrease glucose sensibility, which leads to premature aging and oestrous cycle disruption. Permanent light exposure also leads to accumulation superoxide dismutase and oxidative stress, which is one of the main factors for early dementia and Alzheimer disease. We propose a new screening system adjusted for people, migrating from middle to high latitudes and accommodation therapy. Screening is focused on melatonin and estrogen levels, sleep deprivation and neural disorders, depression level, cancer risks and heart and vascular disorders. Accommodation therapy includes different types artificial light exposure, additional melatonin and neuroprotectors. Preventive procedures can lead to increase of migration intensity to high latitudes and, as a result, the prosperity of Arctic region.

Keywords: circadian rhythm, high latitudes, melatonin, neuroprotectors

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324 Development and Mineral Profile Analysis of Fruit, Vegetable and Wild Herb Based Juices to Be Consumed in Elderly Centres in Durban, South Africa

Authors: Mkhize Xolile, Davies Theopheluis

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The purpose of the study was to develop a variety of fruit, vegetable and indigenous wild herb (amaranth) based juices, which can increase mineral consumption (of Ca, Fe, K, Mg, Zn). Ten samples of juice varieties were developed. The concentration range for the standards was between 10 and 150 ppm. Standards and samples were analysed using Perkin Elmer Atomic Absorption Spectrophotometer and the AAnalyst 400 model was used. The indigenous herb based juice was the most nutritious than all the other varieties developed. Mg and Fe could contribute significantly in improving cardio vascular health, bone functionality and immunity of elderly.

Keywords: minerals, elderly, juice, hypertension, intervention

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323 The Contribution of Genetic Polymorphisms of Tumor Necrosis Factor Alpha and Vascular Endothelial Growth Factor into the Unfavorable Clinical Course of Ulcerative Colitis

Authors: Y. I. Tretyakova, S. G. Shulkina, T. Y. Kravtsova, A. A. Antipova, N. Y. Kolomeets

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The research aimed to assess the functional significance of tumor necrosis factor-alpha (TNF-α) gene polymorphism at the -308G/A (rs1800629) region and vascular endothelial growth factor A (VEGFA) gene polymorphism at the -634G/C (rs 2010963) region in the development of ulcerative colitis (UC), focusing on patients from the Perm region, Russia. We examined 70 UC patients and 50 healthy donors during the active phase of the disease. Our focus was on TNF-α and VEGF concentration in the blood serum, as well as TNF-α and VEGFA gene polymorphisms at the -308G/А and -634G/C regions, respectively. We found that TNF-α and VEGF levels were significantly higher in patients with severe UC and high endoscopic activity compared to those with milder forms of the disease and low endoscopic activity. These tests could serve as additional non-invasive markers for assessing mucosal damage in the large intestine of UC patients. The frequency of allele variations in the TNF-α gene -308G/A (rs1800629) revealed a significantly higher occurrence of the unfavorable homozygote AA in UC patients compared to donors. Additionally, the major allele G and the allele pair GG were more frequent in patients with mild to moderate disease and 1-2 degree of endoscopic activity than in those with severe UC and 3-4 degree of endoscopic activity (χ2=14.19; p=0.000). We also observed a mutant allele A and the unfavorable homozygote AA associated with severe progressive UC. The occurrence of the mutant allele increased the risk of severe UC by 5 times (OR 5.03; CI 12.07-12.21). We did not find any significant differences in the frequency of the CC homozygote (χ2=1.02; p=0.6; OR=1.32) and the mutant allele C of the VEGFA gene -634G/C (rs 2010963) (χ2=0.01; p=0.913; OR=0.97) between groups of UC patients and healthy individuals. However, we detected that the mutant allele C and the unfavorable homozygote CC of the VEGFA gene were associated with more severe endoscopic changes in the colonic mucosa of UC patients (χ2=25,76; р=0,000; OR=0,15). The presence of the mutant allele increased the risk of severe UC by 6 times (OR 6,78; CI 3,13–14,7). We found a direct correlation between TNF-α and VEGFA gene polymorphisms, increased production of the same factors, disease severity, and endoscopic activity (р=0.000). Therefore, the presence of the mutant allele A and homozygote AA of the TNF-α gene at the -308G/A region and the mutant allele C and homozygote CC of the VEGFA gene at the -634G/C region are associated with risks related to an unfavorable clinical course of UC, frequent recurrences, and rapid progression. These findings should be considered when making prognoses regarding the clinical course of the disease and selecting treatment strategies. The presence of the homozygote AA in the TNF-α gene (rs1800629) is considered a sign of genetic predisposition to UC.

Keywords: gene polymorphism, TNF-α, ulcerative colitis, VEGF

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322 Endothelin Cells and Its Molecular Biology and Microbiology

Authors: Chro Kawyan

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Endothelin-1 (ET-1), the principal individual from the newfound mammalian endothelin group of organically dynamic peptides, was initially distinguished as a 21 buildup powerful vasoconstrictor peptide in vascular endothelial cells. However, it has since been demonstrated to have a wide range of pharmacological activities in tissues both inside and outside the cardiovascular system. Additionally, peptides that have a striking resemblance to ET-1 have been identified as the primary toxic component of snake venom. In addition, late examinations have proposed that warm blooded creatures, including people, produce three unmistakable individuals from this peptide family, ET-1, ET-2 and ET-J, which might have various profiles of organic action and may follow up on particular subtypes of endothelin receptor. Masashi Yanagisawa and Tomoh Masaki survey the ongoing status of the organic chemistry and sub-atomic science of endothelin.

Keywords: thelin, microbiology, molecular biology, cell

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321 Renal Amyloidosis in Domestic Iranian Sheep

Authors: Keivan Jamshidi, Fateme Behbahani, Sara Omidi, Nadia Shahi, Alireza Farkhonde

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Amyloidosis represents a heterogenous group of diseases that have in common the deposition of fibrils composed of proteins of beta-pleated sheet structure, which can be specifically identified by histochemistry using the Congo red or similar stains. Between October 2013 to April 2014 (6 months) different patterns of renal amyloidosis was diagnosed on histopathological examination of kidneys belong to 196 out of 7065 slaughtered sheep subjected to postmortem examination. Microscopic examination of renal tissue sections stained with H&E and CR staining techniques revealed 3 patterns of renal amyloid deposition; including glomerular (22.72%), medullary (68.18%), and vascular (9.09%) were recognized. Renal medullary amyloidosis (RMA) was detected as the most prevalence pattern of renal amyloidosis in domestic sheep.

Keywords: sheep, amyloidosis, kidney, slaughterhouse

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320 Safety and Feasibility of Distal Radial Balloon Aortic Valvuloplasty - The DR-BAV Study

Authors: Alexandru Achim, Tamás Szűcsborus, Viktor Sasi, Ferenc Nagy, Zoltán Jambrik, Attila Nemes, Albert Varga, Călin Homorodean, Olivier F. Bertrand, Zoltán Ruzsa

Abstract:

Aim: Our study aimed to establish the safety and the technical success of distal radial access for balloon aortic valvuloplasty (DR-BAV). The secondary objective was to determine the effectiveness and appropriate role of DR-BAV within half year follow-up. Methods: Clinical and angiographic data from 32 consecutive patients with symptomatic aortic stenosis were evaluated in a prospective pilot single-center study. Between 2020 and 2021, the patients were treated utilizing dual distal radial access with 6-10F compatible balloons. The efficacy endpoint was divided into technical success (successful valvuloplasty balloon inflation at the aortic valve and absence of intra- or periprocedural major complications), hemodynamic success (a reduction of the mean invasive gradient >30%), and clinical success (an improvement of at least one clinical category in the NYHA classification). The safety endpoints were vascular complications (major and minor Valve Academic Research Consortium (VARC)-2 bleeding, diminished or lost arterial pulse or the presence of any pseudo-aneurysm or arteriovenous fistula during the clinical follow-up) and major adverse events, MAEs (the composite of death, stroke, myocardial infarction, and urgent major aortic valve replacement or implantation during the hospital stay and or at one-month follow-up). Results: 32 patients (40 % male, mean age 80 ± 8,5) with severe aortic valve stenosis were included in the study and 4 patients were excluded. Technical success was achieved in all patients (100%). Hemodynamic success was achieved in 30 patients (93,75%). Invasive max and mean gradients were reduced from 73±22 mm Hg and 49±22 mm Hg to 49±19 mm Hg and 20±13 mm Hg, respectively (p = <.001). Clinical success was achieved in 29 patients (90,6%). In total, no major adverse cardiac or cerebrovascular event nor vascular complications (according to VARC 2 criteria) occurred during the intervention. All-cause death at 6 months was 12%. Conclusion: According to our study, dual distal radial artery access is a safe and effective option for balloon aortic valvuloplasty in patients with severe aortic valve stenosis and can be performed in all patients with sufficient lumen diameter. Future randomized studies are warranted to investigate whether this technique is superior to other approaches.

Keywords: mean invasive gradient, distal radial access for balloon aortic valvuloplasty (DR-BAV), aortic valve stenosis, pseudo-aneurysm, arteriovenous fistula, valve academic research consortium (VARC)-2

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319 Consumption and Diffusion Based Model of Tissue Organoid Development

Authors: Elena Petersen, Inna Kornienko, Svetlana Guryeva, Sergey Simakov

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In vitro organoid cultivation requires the simultaneous provision of necessary vascularization and nutrients perfusion of cells during organoid development. However, many aspects of this problem are still unsolved. The functionality of vascular network intergrowth is limited during early stages of organoid development since a function of the vascular network initiated on final stages of in vitro organoid cultivation. Therefore, a microchannel network should be created in early stages of organoid cultivation in hydrogel matrix aimed to conduct and maintain minimally required the level of nutrients perfusion for all cells in the expanding organoid. The network configuration should be designed properly in order to exclude hypoxic and necrotic zones in expanding organoid at all stages of its cultivation. In vitro vascularization is currently the main issue within the field of tissue engineering. As perfusion and oxygen transport have direct effects on cell viability and differentiation, researchers are currently limited only to tissues of few millimeters in thickness. These limitations are imposed by mass transfer and are defined by the balance between the metabolic demand of the cellular components in the system and the size of the scaffold. Current approaches include growth factor delivery, channeled scaffolds, perfusion bioreactors, microfluidics, cell co-cultures, cell functionalization, modular assembly, and in vivo systems. These approaches may improve cell viability or generate capillary-like structures within a tissue construct. Thus, there is a fundamental disconnect between defining the metabolic needs of tissue through quantitative measurements of oxygen and nutrient diffusion and the potential ease of integration into host vasculature for future in vivo implantation. A model is proposed for growth prognosis of the organoid perfusion based on joint simulations of general nutrient diffusion, nutrient diffusion to the hydrogel matrix through the contact surfaces and microchannels walls, nutrient consumption by the cells of expanding organoid, including biomatrix contraction during tissue development, which is associated with changed consumption rate of growing organoid cells. The model allows computing effective microchannel network design giving minimally required the level of nutrients concentration in all parts of growing organoid. It can be used for preliminary planning of microchannel network design and simulations of nutrients supply rate depending on the stage of organoid development.

Keywords: 3D model, consumption model, diffusion, spheroid, tissue organoid

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318 Synthesis and Anticholinesterase Activity of Carvacrol Derivatives

Authors: Fatih Sonmez

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease and it is the most common form of dementia that affects aged people. Acetylcholinesterase is a hydrolase involved in the termination of impulse transmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter ACh in the central and peripheral nervous system. Carvacrol (5-iso-propyl-2-methyl-phenol) is a main bioactive monoterpene isolated from many medicinal herbs, such as Thymus vulgaris, Monarda punctate and Origanum vulgare spp. It is known that carvacrol has been widely used as an active anti-inflammatory ingredient, which can inhibit the isoproterenol induced inflammation in myocardial infarcted rats. In this paper, a series of 12 carvacrol substituted carbamate derivatives (2a-l) was synthesized and their inhibitory activities on AChE and BuChE were evaluated. Among them, 2d exhibited the strongest inhibition against AChE with an IC50 value of 2.22 µM, which was 130-fold more than that of carvacrol (IC50 = 288.26 µM).

Keywords: Acetylcholinesterase, Butyrylcholinesterase, Carbamate, Carvacrol

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317 Envy and Schadenfreude Domains in a Model of Neurodegeneration

Authors: Hernando Santamaría-García, Sandra Báez, Pablo Reyes, José Santamaría-García, Diana Matallana, Adolfo García, Agustín Ibañez

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The study of moral emotions (i.e., Schadenfreude and envy) is critical to understand the ecological complexity of everyday interactions between cognitive, affective, and social cognition processes. Most previous studies in this area have used correlational imaging techniques and framed Schadenfreude and envy as monolithic domains. Here, we profit from a relevant neurodegeneration model to disentangle the brain regions engaged in three dimensions of Schadenfreude and envy: deservingness, morality, and legality. We tested 20 patients with behavioral variant frontotemporal dementia (bvFTD), 24 patients with Alzheimer’s disease (AD), as a contrastive neurodegeneration model, and 20 healthy controls on a novel task highlighting each of these dimensions in scenarios eliciting Schadenfreude and envy. Compared with the AD and control groups, bvFTD patients obtained significantly higher scores on all dimensions for both emotions. Interestingly, the legal dimension for both envy and Schadenfreude elicited higher emotional scores than the deservingness and moral dimensions. Furthermore, correlational analyses in bvFTD showed that higher envy and Schadenfreude scores were associated with greater deficits in social cognition, inhibitory control, and behavior. Brain anatomy findings (restricted to bvFTD and controls) confirmed differences in how these groups process each dimension. Schadenfreude was associated with the ventral striatum in all subjects. Also, in bvFTD patients, increased Schadenfreude across dimensions was negatively correlated with regions supporting social-value rewards, mentalizing, and social cognition (frontal pole, temporal pole, angular gyrus and precuneus). In all subjects, all dimensions of envy positively correlated with the volume of the anterior cingulate cortex, a region involved in processing unfair social comparisons. By contrast, in bvFTD patients, the intensified experience of envy across all dimensions was negatively correlated with a set of areas subserving social cognition, including the prefrontal cortex, the parahippocampus, and the amygdala. Together, the present results provide the first lesion-based evidence for the multidimensional nature of the emotional experiences of envy and Schadenfreude. Moreover, this is the first demonstration of a selective exacerbation of envy and Schadenfreude in bvFTD patients, probably triggered by atrophy to social cognition networks. Our results offer new insights into the mechanisms subserving complex emotions and moral cognition in neurodegeneration, paving the way for groundbreaking research on their interaction with other cognitive, social, and emotional processes.

Keywords: social cognition, moral emotions, neuroimaging, frontotemporal dementia

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316 Amyloid-β Fibrils Remodeling by an Organic Molecule: Insight from All-Atomic Molecular Dynamics Simulations

Authors: Nikhil Agrawal, Adam A. Skelton

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Alzheimer’s disease (AD) is one of the most common forms of dementia, which is caused by misfolding and aggregation of amyloid beta (Aβ) peptides into amyloid-β fibrils (Aβ fibrils). To disrupt the remodeling of Aβ fibrils, a number of candidate molecules have been proposed. To study the molecular mechanisms of Aβ fibrils remodeling we performed a series of all-atom molecular dynamics simulations, a total time of 3µs, in explicit solvent. Several previously undiscovered candidate molecule-Aβ fibrils binding modes are unraveled; one of which shows the direct conformational change of the Aβ fibril by understanding the physicochemical factors responsible for binding and subsequent remodeling of Aβ fibrils by the candidate molecule, open avenues into structure-based drug design for AD can be opened.

Keywords: alzheimer’s disease, amyloid, MD simulations, misfolded protein

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315 Machine Learning Based Digitalization of Validated Traditional Cognitive Tests and Their Integration to Multi-User Digital Support System for Alzheimer’s Patients

Authors: Ramazan Bakir, Gizem Kayar

Abstract:

It is known that Alzheimer and Dementia are the two most common types of Neurodegenerative diseases and their visibility is getting accelerated for the last couple of years. As the population sees older ages all over the world, researchers expect to see the rate of this acceleration much higher. However, unfortunately, there is no known pharmacological cure for both, although some help to reduce the rate of cognitive decline speed. This is why we encounter with non-pharmacological treatment and tracking methods more for the last five years. Many researchers, including well-known associations and hospitals, lean towards using non-pharmacological methods to support cognitive function and improve the patient’s life quality. As the dementia symptoms related to mind, learning, memory, speaking, problem-solving, social abilities and daily activities gradually worsen over the years, many researchers know that cognitive support should start from the very beginning of the symptoms in order to slow down the decline. At this point, life of a patient and caregiver can be improved with some daily activities and applications. These activities include but not limited to basic word puzzles, daily cleaning activities, taking notes. Later, these activities and their results should be observed carefully and it is only possible during patient/caregiver and M.D. in-person meetings in hospitals. These meetings can be quite time-consuming, exhausting and financially ineffective for hospitals, medical doctors, caregivers and especially for patients. On the other hand, digital support systems are showing positive results for all stakeholders of healthcare systems. This can be observed in countries that started Telemedicine systems. The biggest potential of our system is setting the inter-user communication up in the best possible way. In our project, we propose Machine Learning based digitalization of validated traditional cognitive tests (e.g. MOCA, Afazi, left-right hemisphere), their analyses for high-quality follow-up and communication systems for all stakeholders. R. Bakir and G. Kayar are with Gefeasoft, Inc, R&D – Software Development and Health Technologies company. Emails: ramazan, gizem @ gefeasoft.com This platform has a high potential not only for patient tracking but also for making all stakeholders feel safe through all stages. As the registered hospitals assign corresponding medical doctors to the system, these MDs are able to register their own patients and assign special tasks for each patient. With our integrated machine learning support, MDs are able to track the failure and success rates of each patient and also see general averages among similarly progressed patients. In addition, our platform also supports multi-player technology which helps patients play with their caregivers so that they feel much safer at any point they are uncomfortable. By also gamifying the daily household activities, the patients will be able to repeat their social tasks and we will provide non-pharmacological reminiscence therapy (RT – life review therapy). All collected data will be mined by our data scientists and analyzed meaningfully. In addition, we will also add gamification modules for caregivers based on Naomi Feil’s Validation Therapy. Both are behaving positively to the patient and keeping yourself mentally healthy is important for caregivers. We aim to provide a therapy system based on gamification for them, too. When this project accomplishes all the above-written tasks, patients will have the chance to do many tasks at home remotely and MDs will be able to follow them up very effectively. We propose a complete platform and the whole project is both time and cost-effective for supporting all stakeholders.

Keywords: alzheimer’s, dementia, cognitive functionality, cognitive tests, serious games, machine learning, artificial intelligence, digitalization, non-pharmacological, data analysis, telemedicine, e-health, health-tech, gamification

Procedia PDF Downloads 111
314 Integrating Computational Modeling and Analysis with in Vivo Observations for Enhanced Hemodynamics Diagnostics and Prognosis

Authors: Shreyas S. Hegde, Anindya Deb, Suresh Nagesh

Abstract:

Computational bio-mechanics is developing rapidly as a non-invasive tool to assist the medical fraternity to help in both diagnosis and prognosis of human body related issues such as injuries, cardio-vascular dysfunction, atherosclerotic plaque etc. Any system that would help either properly diagnose such problems or assist prognosis would be a boon to the doctors and medical society in general. Recently a lot of work is being focused in this direction which includes but not limited to various finite element analysis related to dental implants, skull injuries, orthopedic problems involving bones and joints etc. Such numerical solutions are helping medical practitioners to come up with alternate solutions for such problems and in most cases have also reduced the trauma on the patients. Some work also has been done in the area related to the use of computational fluid mechanics to understand the flow of blood through the human body, an area of hemodynamics. Since cardio-vascular diseases are one of the main causes of loss of human life, understanding of the blood flow with and without constraints (such as blockages), providing alternate methods of prognosis and further solutions to take care of issues related to blood flow would help save valuable life of such patients. This project is an attempt to use computational fluid dynamics (CFD) to solve specific problems related to hemodynamics. The hemodynamics simulation is used to gain a better understanding of functional, diagnostic and theoretical aspects of the blood flow. Due to the fact that many fundamental issues of the blood flow, like phenomena associated with pressure and viscous forces fields, are still not fully understood or entirely described through mathematical formulations the characterization of blood flow is still a challenging task. The computational modeling of the blood flow and mechanical interactions that strongly affect the blood flow patterns, based on medical data and imaging represent the most accurate analysis of the blood flow complex behavior. In this project the mathematical modeling of the blood flow in the arteries in the presence of successive blockages has been analyzed using CFD technique. Different cases of blockages in terms of percentages have been modeled using commercial software CATIA V5R20 and simulated using commercial software ANSYS 15.0 to study the effect of varying wall shear stress (WSS) values and also other parameters like the effect of increase in Reynolds number. The concept of fluid structure interaction (FSI) has been used to solve such problems. The model simulation results were validated using in vivo measurement data from existing literature

Keywords: computational fluid dynamics, hemodynamics, blood flow, results validation, arteries

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313 Amifostine Analogue, Drde-30, Attenuates Radiation-Induced Lung Injury in Mice

Authors: Aastha Arora, Vikas Bhuria, Saurabh Singh, Uma Pathak, Shweta Mathur, Puja P. Hazari, Rajat Sandhir, Ravi Soni, Anant N. Bhatt, Bilikere S. Dwarakanath

Abstract:

Radiotherapy is an effective curative and palliative option for patients with thoracic malignancies. However, lung injury, comprising of pneumonitis and fibrosis, remains a significant clin¬ical complication of thoracic radiation, thus making it a dose-limiting factor. Also, injury to the lung is often reported as part of multi-organ failure in victims of accidental radiation exposures. Radiation induced inflammatory response in the lung, characterized by leukocyte infiltration and vascular changes, is an important contributing factor for the injury. Therefore, countermeasure agents to attenuate radiation induced inflammatory response are considered as an important approach to prevent chronic lung damage. Although Amifostine, the widely used, FDA approved radio-protector, has been found to reduce the radiation induced pneumonitis during radiation therapy of non-small cell lung carcinoma, its application during mass and field exposure is limited due to associated toxicity and ineffectiveness with the oral administration. The amifostine analogue (DRDE-30) overcomes this limitation as it is orally effective in reducing the mortality of whole body irradiated mice. The current study was undertaken to investigate the potential of DRDE-30 to ameliorate radiation induced lung damage. DRDE-30 was administered intra-peritoneally, 30 minutes prior to 13.5 Gy thoracic (60Co-gamma) radiation in C57BL/6 mice. Broncheo- alveolar lavage fluid (BALF) and lung tissues were harvested at 12 and 24 weeks post irradiation for studying inflammatory and fibrotic markers. Lactate dehydrogenase (LDH) leakage, leukocyte count and protein content in BALF were used as parameters to evaluate lung vascular permeability. Inflammatory cell signaling (p38 phosphorylation) and anti-oxidant status (MnSOD and Catalase level) was assessed by Western blot, while X-ray CT scan, H & E staining and trichrome staining were done to study the lung architecture and collagen deposition. Irradiation of the lung increased the total protein content, LDH leakage and total leukocyte count in the BALF, reflecting endothelial barrier dysfunction. These disruptive effects were significantly abolished by DRDE-30, which appear to be linked to the DRDE-30 mediated abrogation of activation of the redox-sensitive pro- inflammatory signaling cascade, the MAPK pathway. Concurrent administration of DRDE-30 with radiation inhibited radiation-induced oxidative stress by strengthening the anti-oxidant defense system and abrogated p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and macrophage recruitment to the lungs. Histopathological examination (by H & E staining) of the lung showed radiation-induced inflammation of the lungs, characterized by cellular infiltration, interstitial oedema, alveolar wall thickening, perivascular fibrosis and obstruction of alveolar spaces, which were all reduced by pre-administration of DRDE-30. Structural analysis with X-ray CT indicated lung architecture (linked to the degree of opacity) comparable to un-irradiated mice that correlated well with the lung morphology and reduced collagen deposition. Reduction in the radiation-induced inflammation and fibrosis brought about by DRDE-30 resulted in a profound increase in animal survival (72 % in the combination vs 24% with radiation) observed at the end of 24 weeks following irradiation. These findings establish the potential of the Amifostine analogue, DRDE-30, in reducing radiation induced pulmonary injury by attenuating the inflammatory and fibrotic responses.

Keywords: amifostine, fibrosis, inflammation, lung injury radiation

Procedia PDF Downloads 487
312 Phase Synchronization of Skin Blood Flow Oscillations under Deep Controlled Breathing in Human

Authors: Arina V. Tankanag, Gennady V. Krasnikov, Nikolai K. Chemeris

Abstract:

The development of respiration-dependent oscillations in the peripheral blood flow may occur by at least two mechanisms. The first mechanism is related to the change of venous pressure due to mechanical activity of lungs. This phenomenon is known as ‘respiratory pump’ and is one of the mechanisms of venous return of blood from the peripheral vessels to the heart. The second mechanism is related to the vasomotor reflexes controlled by the respiratory modulation of the activity of centers of the vegetative nervous system. Early high phase synchronization of respiration-dependent blood flow oscillations of left and right forearm skin in healthy volunteers at rest was shown. The aim of the work was to study the effect of deep controlled breathing on the phase synchronization of skin blood flow oscillations. 29 normotensive non-smoking young women (18-25 years old) of the normal constitution without diagnosed pathologies of skin, cardiovascular and respiratory systems participated in the study. For each of the participants six recording sessions were carried out: first, at the spontaneous breathing rate; and the next five, in the regimes of controlled breathing with fixed breathing depth and different rates of enforced breathing regime. The following rates of controlled breathing regime were used: 0.25, 0.16, 0.10, 0.07 and 0.05 Hz. The breathing depth amounted to 40% of the maximal chest excursion. Blood perfusion was registered by laser flowmeter LAKK-02 (LAZMA, Russia) with two identical channels (wavelength 0.63 µm; emission power, 0.5 mW). The first probe was fastened to the palmar surface of the distal phalanx of left forefinger; the second probe was attached to the external surface of the left forearm near the wrist joint. These skin zones were chosen as zones with different dominant mechanisms of vascular tonus regulation. The degree of phase synchronization of the registered signals was estimated from the value of the wavelet phase coherence. The duration of all recording was 5 min. The sampling frequency of the signals was 16 Hz. The increasing of synchronization of the respiratory-dependent skin blood flow oscillations for all controlled breathing regimes was obtained. Since the formation of respiration-dependent oscillations in the peripheral blood flow is mainly caused by the respiratory modulation of system blood pressure, the observed effects are most likely dependent on the breathing depth. It should be noted that with spontaneous breathing depth does not exceed 15% of the maximal chest excursion, while in the present study the breathing depth was 40%. Therefore it has been suggested that the observed significant increase of the phase synchronization of blood flow oscillations in our conditions is primarily due to an increase of breathing depth. This is due to the enhancement of both potential mechanisms of respiratory oscillation generation: venous pressure and sympathetic modulation of vascular tone.

Keywords: deep controlled breathing, peripheral blood flow oscillations, phase synchronization, wavelet phase coherence

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311 Multidisciplinary Approach to Diagnosis of Primary Progressive Aphasia in a Younger Middle Aged Patient

Authors: Robert Krause

Abstract:

Primary progressive aphasia (PPA) is a neurodegenerative disease similar to frontotemporal and semantic dementia, while having a different clinical image and anatomic pathology topography. Nonetheless, they are often included under an umbrella term: frontotemporal lobar degeneration (FTLD). In the study, examples of diagnosing PPA are presented through the multidisciplinary lens of specialists from different fields (neurologists, psychiatrists, clinical speech therapists, clinical neuropsychologists and others) using a variety of diagnostic tools such as MR, PET/CT, genetic screening and neuropsychological and logopedic methods. Thanks to that, specialists can get a better and clearer understanding of PPA diagnosis. The study summarizes the concrete procedures and results of different specialists while diagnosing PPA in a patient of younger middle age and illustrates the importance of multidisciplinary approach to differential diagnosis of PPA.

Keywords: primary progressive aphasia, etiology, diagnosis, younger middle age

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310 Pharmacognostical and Phytochemical Investigation of the Endemic Medicinal Plant Tekchebilium arvensis Linn

Authors: K. Bengango, H. Mesahsah, F. Haseb-Reho, J. M. Tafrate

Abstract:

This present work was conducted to explore the micro-morphology and phytochemical characterization of the endemic medicinal plant Tekchebilium arvensis Linn (Asteraceae). Macroscopy, microscopy, physicochemical analysis and WHO recommended parameters for standardizations were performed. Microscopic evaluation revealed the presence of abaxial epidermis with paracytic stomata. Petiole showed epidermis, vascular strands, ground tissue and secretary cavities. Physico-chemical tests like ash values, loss on drying, extractive values were determined. Preliminary phytochemical screening showed the presence of sterols, tannins, flavonoids, glycosides, volatile oil, terpenoids, saponin and alkaloids.

Keywords: Tekchebilium arvensis Linn, Asteraceae, microscopical evaluation, phytochemical, powder microscopy, standardization

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309 The Act of Care: Reimagined Rituals towards Unattachment

Authors: Ioana G. Turcan

Abstract:

reimagined rituals towards unattachment wants to look at an ambiguous loss through the perspective of caregivers, those that accompany us at the beginning and possibly the end of life, those that observe, accumulate, and are impacted by our behavior and needs, but also those that are the witnesses of the human vulnerability. Someone taking care of a patient with dementia experiences ambiguous loss, being in a present of a person partially present, partially absent. The one offering care needs care, not isolation and the aim of the project is to consolidate existing communities or engage other possible ones using performance, storytelling, and other artistic methods. The long-term aim is that with community work, we will manage to co-create rituals in order to help us live with this kind of loss. Looking at them through the lens of different cultures and individuals exercises both the ability to extract the universal essence of a ritual, but also the need and freedom to express the specificity of each situation. To be seen and acknowledged by others, but more importantly, to see oneself from outside with dignity, is very powerful. Oftentimes we forget to express, look and appreciate our own stories, and instead, we choose to outcast them.

Keywords: grief, socio-politics of loss, ambiguous loss, rituals

Procedia PDF Downloads 152
308 Incidences and Factors Associated with Perioperative Cardiac Arrest in Trauma Patient Receiving Anesthesia

Authors: Visith Siriphuwanun, Yodying Punjasawadwong, Suwinai Saengyo, Kittipan Rerkasem

Abstract:

Objective: To determine incidences and factors associated with perioperative cardiac arrest in trauma patients who received anesthesia for emergency surgery. Design and setting: Retrospective cohort study in trauma patients during anesthesia for emergency surgery at a university hospital in northern Thailand country. Patients and methods: This study was permitted by the medical ethical committee, Faculty of Medicine at Maharaj Nakorn Chiang Mai Hospital, Thailand. We clarified data of 19,683 trauma patients receiving anesthesia within a decade between January 2007 to March 2016. The data analyzed patient characteristics, traumas surgery procedures, anesthesia information such as ASA physical status classification, anesthesia techniques, anesthetic drugs, location of anesthesia performed, and cardiac arrest outcomes. This study excluded the data of trauma patients who had received local anesthesia by surgeons or monitoring anesthesia care (MAC) and the patient which missing more information. The factor associated with perioperative cardiac arrest was identified with univariate analyses. Multiple regressions model for risk ratio (RR) and 95% confidence intervals (CI) were used to conduct factors correlated with perioperative cardiac arrest. The multicollinearity of all variables was examined by bivariate correlation matrix. A stepwise algorithm was chosen at a p-value less than 0.02 was selected to further multivariate analysis. A P-value of less than 0.05 was concluded as statistically significant. Measurements and results: The occurrence of perioperative cardiac arrest in trauma patients receiving anesthesia for emergency surgery was 170.04 per 10,000 cases. Factors associated with perioperative cardiac arrest in trauma patients were age being more than 65 years (RR=1.41, CI=1.02–1.96, p=0.039), ASA physical status 3 or higher (RR=4.19–21.58, p < 0.001), sites of surgery (intracranial, intrathoracic, upper intra-abdominal, and major vascular, each p < 0.001), cardiopulmonary comorbidities (RR=1.55, CI=1.10–2.17, p < 0.012), hemodynamic instability with shock prior to receiving anesthesia (RR=1.60, CI=1.21–2.11, p < 0.001) , special techniques for surgery such as cardiopulmonary bypass (CPB) and hypotensive techniques (RR=5.55, CI=2.01–15.36, p=0.001; RR=6.24, CI=2.21–17.58, p=0.001, respectively), and patients who had a history of being alcoholic (RR=5.27, CI=4.09–6.79, p < 0.001). Conclusion: Incidence of perioperative cardiac arrest in trauma patients receiving anesthesia for emergency surgery was very high and correlated with many factors, especially age of patient and cardiopulmonary comorbidities, patient having a history of alcoholic addiction, increasing ASA physical status, preoperative shock, special techniques for surgery, and sites of surgery including brain, thorax, abdomen, and major vascular region. Anesthesiologists and multidisciplinary teams in pre- and perioperative periods should remain alert for warning signs of pre-cardiac arrest and be quick to manage the high-risk group of surgical trauma patients. Furthermore, a healthcare policy should be promoted for protecting against accidents in high-risk groups of the population as well.

Keywords: perioperative cardiac arrest, trauma patients, emergency surgery, anesthesia, factors risk, incidence

Procedia PDF Downloads 143
307 Applicability of Polyisobutylene-Based Polyurethane Structures in Biomedical Disciplines: Some Calcification and Protein Adsorption Studies

Authors: Nihan Nugay, Nur Cicek Kekec, Kalman Toth, Turgut Nugay, Joseph P. Kennedy

Abstract:

In recent years, polyurethane structures are paving the way for elastomer usage in biology, human medicine, and biomedical application areas. Polyurethanes having a combination of high oxidative and hydrolytic stability and excellent mechanical properties are focused due to enhancing the usage of PUs especially for implantable medical device application such as cardiac-assist. Currently, unique polyurethanes consisting of polyisobutylenes as soft segments and conventional hard segments, named as PIB-based PUs, are developed with precise NCO/OH stoichiometry (∽1.05) for obtaining PIB-based PUs with enhanced properties (i.e., tensile stress increased from ∽11 to ∽26 MPa and elongation from ∽350 to ∽500%). Static and dynamic mechanical properties were optimized by examining stress-strain graphs, self-organization and crystallinity (XRD) traces, rheological (DMA, creep) profiles and thermal (TGA, DSC) responses. Annealing procedure was applied for PIB-based PUs. Annealed PIB-based PU shows ∽26 MPa tensile strength, ∽500% elongation, and ∽77 Microshore hardness with excellent hydrolytic and oxidative stability. The surface characters of them were examined with AFM and contact angle measurements. Annealed PIB-based PU exhibits the higher segregation of individual segments and surface hydrophobicity thus annealing significantly enhances hydrolytic and oxidative stability by shielding carbamate bonds by inert PIB chains. According to improved surface and microstructure characters, greater efforts are focused on analyzing protein adsorption and calcification profiles. In biomedical applications especially for cardiological implantations, protein adsorption inclination on polymeric heart valves is undesirable hence protein adsorption from blood serum is followed by platelet adhesion and subsequent thrombus formation. The protein adsorption character of PIB-based PU examines by applying Bradford assay in fibrinogen and bovine serum albumin solutions. Like protein adsorption, calcium deposition on heart valves is very harmful because vascular calcification has been proposed activation of osteogenic mechanism in the vascular wall, loss of inhibitory factors, enhance bone turnover and irregularities in mineral metabolism. The calcium deposition on films are characterized by incubating samples in simulated body fluid solution and examining SEM images and XPS profiles. PIB-based PUs are significantly more resistant to hydrolytic-oxidative degradation, protein adsorption and calcium deposition than ElastEonTM E2A, a commercially available PDMS-based PU, widely used for biomedical applications.

Keywords: biomedical application, calcification, polyisobutylene, polyurethane, protein adsorption

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306 Transarterial Chemoembolization (TACE) in Hepatocellular Carcinoma (HCC)

Authors: Ilirian Laçi, Alketa Spahiu

Abstract:

Modality of treatment in hepatocellular carcinoma (HCC) patients depends on the stage of the disease. The Barcelona Clinic Liver Cancer Classification (BCLC) is the preferred staging system. There are many patients initially present with intermediate-stage disease. For these patients, transarterial chemoembolization (TACE) is the treatment of choice. The differences in individual factors that are not captured by the BCLC framework, such as the tumor growth pattern, degree of hypervascularity, and vascular supply, complicate further evaluation of these patients. Because of these differences, not all patients benefit equally from TACE. Several tools have been devised to aid the decision-making process, which have shown promising initial results but have failed external evaluation and have not been translated to the clinic aspects. Criteria for treatment decisions in daily clinical practice are needed in all stages of the disease.

Keywords: hepatocellular carcinoma, transarterial chemoembolization, TACE, liver

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305 Follicular Thyroid Carcinoma in a Developing Country: A Retrospective Study of 10 Years

Authors: Abdul Aziz, Muhammad Qamar Masood, Saadia Sattar, Saira Fatima, Najmul Islam

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Introduction: The most common endocrine tumor is thyroid cancer. Follicular Thyroid Carcinoma (FTC) accounts for 5%–10% of all thyroid cancers. Patients with FTC frequently present with more advanced stage diseases and a higher occurrence of distant metastases because of the propensity of vascular invasion. FTC is mainly treated with surgery, while radioactive iodine therapy is the main adjuvant therapy as per ATA guidelines. In many developing countries, surgical facilities and radioactive iodine are in short supply; therefore, understanding follicular thyroid cancer trends may help developing countries plan and use resources more effectively. Methodology: It was a retrospective observational study of FTC patients of age 18 years and above conducted at Aga Khan University Hospital, Karachi, from 1st January 2010 to 31st December 2019. Results: There were 404 patients with thyroid carcinoma, out of which forty (10.1%) were FTC. 50% of the patients were in the 41-60 years age group, and the female to male ratio was 1.5: 1. Twenty-four patients (60%) presented with complain of neck swelling followed by metastasis (20%) and compressive symptoms (20%). The most common site of metastasis was bone (87.5%), followed by lung (12.5%). The pre-operative thyroglobulin level was done in six out of eight metastatic patients (75%) in which it was elevated. This emphasizes the importance of checking thyroglobulin level in unusual presentation (bone pain, fractures) of a patient having neck swelling also to help in establishing the primary source of tumor. There was no complete documentation of ultrasound features of the thyroid gland in all the patients, which is an important investigation done in the initial evaluation of thyroid nodule. On FNAC, 50% (20 patients) had Bethesda category III-IV nodules, while 10% ( 4 patients ) had Bethesda category II. In sixteen patients, FNAC was not done as they presented with compressive symptoms or metastasis. Fifty percent had a total thyroidectomy and 50% had subtotal followed by completion thyroidectomy, plus ten patients had lymph node dissection, out of which seven had histopathological lymph node involvement. On histopathology, twenty-three patients (57.5%) had minimally invasive, while seventeen (42.5%) had widely invasive follicular thyroid carcinoma. The capsular invasion was present in thirty-three patients (82.5%); one patient had no capsular invasion, but there was a vascular invasion. Six patients' histopathology had no record of capsular invasion. In contrast, the lymphovascular invasion was present in twenty-six patients (65%). In this study, 65 % of the patients had clinical stage 1 disease, while 25% had stage 2 and 10% had clinical stage 4. Seventeen patients (42.5%) had received RAI 30-100 mCi, while ten patients (25%) received more than 100 mCi. Conclusion: FTC demographic and clinicopathological presentation are the same in Pakistan as compared to other countries. Surgery followed by RAI is the mainstay of treatment. Thus understanding the trend of FTC and proper planning and utilization of the resources will help the developing countries in effectively treating the FTC.

Keywords: thyroid carcinoma, follicular thyroid carcinoma, clinicopathological features, developing countries

Procedia PDF Downloads 159
304 The Association of Cone-Shaped Epiphysis and Poland Syndrome: A Case Report

Authors: Mohammad Alqattan, Tala Alkhunani, Reema Al, Aldawish, Felwa Almurshard, Abdullah Alzahrani

Abstract:

: Poland’s Syndrome is a congenital anomaly with two clinical features : unilateral agenesis of the pectoralis major and ipsilateral hand symbrachydactyly. Case presentation: We report a rare case of bilateral Poland’s syndrome with several unique features. Discussion: Poland’s syndrome is thought to be due to a vascular insult to the subclavian axis around the 6th week of gestation. Our patient has multiple rare and unique features of Poland’s syndrome. Conclusion: To our best knowledge, for the first time in the literature we associate Poland’s syndrome with cone-shaped epiphysis of the metacarpals of all fingers. Bilaterality, cleft hand deformity, and dextrocardia, were also rare features in our patient.

Keywords: Poland's syndrome, cleft hand deformity, bilaterality, dextrocardia, cone-shaped epiphysis

Procedia PDF Downloads 100
303 Activation of TNF-α from Human Endothelial Cells by Exposure of the Mitochondrial Stress Protein (Hsp60) Secreted from THP-1 Monocytes to High Glucose

Authors: Ryan D. Martinus

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Inflammation of the endothelium is an important process leading to diabetic atherosclerosis. However, the molecular mechanisms by which diabetes contributes to endothelial inflammation remain to be established. Using In-vitro cultured Human cells and Hsp60 specific ELISA assays, we show that Hsp60 is not only induced in Human monocyte cells under hyperglycaemic conditions but that the Hsp60 is also secreted from these cells. Furthermore, we also demonstrate that the Hsp60 secreted from these monocyte cells is also able to activate Toll-like receptor-4 (TLR4) from Human endothelial cells. This suggests that a potential link may exist between the hyperglycaemia-induced expression of Hsp60 in monocyte cells and vascular inflammation. Circulating levels of Hsp60 due to mitochondrial stress in diabetes patients could, therefore, be an important modulator of inflammation in endothelial cells and thus contribute to the increased incidences of atherosclerosis in diabetes mellitus.

Keywords: mitochondria, Hsp60, inflammation, diabetes mellitus

Procedia PDF Downloads 150
302 Behavioral and Cultural Risk Factor of Cardiovascular Disease in India: Evidence from SAGE-Study

Authors: Sunita Patel

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Cardiovascular diseases are the leading cause of morbidity as well as mortality in India. Objective of this study is to examine CVDs prevalence and identify their behavioral and cultural risk factors with the help of SAGE-2007 data conducted on 6th states in India. Findings reveal that 18.3% of people diagnosed with CVDs in India. Higher disease occurs in an increasing rate between ages of 30-39 having OR 2.45 (CI: 1.66-3.63) and 70+ age OR 7.45 (CI: 4.82-11.49) times higher compare to 18-29 age group respectively. Wealth quintile higher CVD occurs as 3rd in 60% (CI: 1.16-2.21) and in richest 5th quintile 58% (CI: 1.13-2.21) contrast to lowest quintile. Relative risk depicted that 22.4% in moderate and 44% in vigorous activity have less chance of diseases compare to who performed no work and those who consumed alcohol. Results reveal that policy prospect should be recommended and that it would be beneficial for awareness of people and their future.

Keywords: behavioral risk, cultural risk, cardio-vascular diseases, wealth quintile

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