Search results for: peripheral blood leukocytes
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2716

Search results for: peripheral blood leukocytes

2086 The Implantable MEMS Blood Pressure Sensor Model With Wireless Powering And Data Transmission

Authors: Vitaliy Petrov, Natalia Shusharina, Vitaliy Kasymov, Maksim Patrushev, Evgeny Bogdanov

Abstract:

The leading worldwide death reasons are ischemic heart disease and other cardiovascular illnesses. Generally, the common symptom is high blood pressure. Long-time blood pressure control is very important for the prophylaxis, correct diagnosis and timely therapy. Non-invasive methods which are based on Korotkoff sounds are impossible to apply often and for a long time. Implantable devices can combine longtime monitoring with high accuracy of measurements. The main purpose of this work is to create a real-time monitoring system for decreasing the death rate from cardiovascular diseases. These days implantable electronic devices began to play an important role in medicine. Usually implantable devices consist of a transmitter, powering which could be wireless with a special made battery and measurement circuit. Common problems in making implantable devices are short lifetime of the battery, big size and biocompatibility. In these work, blood pressure measure will be the focus because it’s one of the main symptoms of cardiovascular diseases. Our device will consist of three parts: the implantable pressure sensor, external transmitter and automated workstation in a hospital. The Implantable part of pressure sensors could be based on piezoresistive or capacitive technologies. Both sensors have some advantages and some limitations. The Developed circuit is based on a small capacitive sensor which is made of the technology of microelectromechanical systems (MEMS). The Capacitive sensor can provide high sensitivity, low power consumption and minimum hysteresis compared to the piezoresistive sensor. For this device, it was selected the oscillator-based circuit where frequency depends from the capacitance of sensor hence from capacitance one can calculate pressure. The external device (transmitter) used for wireless charging and signal transmission. Some implant devices for these applications are passive, the external device sends radio wave signal on internal LC circuit device. The external device gets reflected the signal from the implant and from a change of frequency is possible to calculate changing of capacitance and then blood pressure. However, this method has some disadvantages, such as the patient position dependence and static using. Developed implantable device doesn’t have these disadvantages and sends blood pressure data to the external part in real-time. The external device continuously sends information about blood pressure to hospital cloud service for analysis by a physician. Doctor’s automated workstation at the hospital also acts as a dashboard, which displays actual medical data of patients (which require attention) and stores it in cloud service. Usually, critical heart conditions occur few hours before heart attack but the device is able to send an alarm signal to the hospital for an early action of medical service. The system was tested with wireless charging and data transmission. These results can be used for ASIC design for MEMS pressure sensor.

Keywords: MEMS sensor, RF power, wireless data, oscillator-based circuit

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2085 Antidiabetic and Antihyperlipaemic Effects of Aqueous Neem (Azadirachta Indica) Extract on Alloxan Diabetic Rabbits

Authors: Khalil Abdullah Ahmed Khalil, Elsadig Mohamed Ahmed

Abstract:

Extracts of various plants material capable of decreasing blood sugar have been tested in experimental animal models and their effects confirmed. Neem or Margose (Azadirachta Indica) is an indigenous plant believed to have antiviral, antifungal, antidiabetic and many other properties. This paper deals with a comparative study of the effect of aqueous Neem leaves extract alone or in combination with glibenclamide on alloxan diabetic rabbits. Administration of crude aqueous Neem extract (CANE) alone (1.5 ml/kg/day), as well as the combination of CANE (1.5 ml/kg/day) with glibenclamide (0.25 mg/kg/day) significantly, decreased (P<0.05) the concentrations of serum lipids, blood glucose and lipoprotein VLDL(very low-density lipoproteins) and LDL(low-density lipoproteins) but significantly increased (P<0.05) the concentration of HDL(high-density lipoprotein). The change was observed significantly greater when the treatment was given in combination of CANE and glibenclamid than with CANE alone.

Keywords: neem, hypoglycemic, hypolipidemic, cholesterol

Procedia PDF Downloads 265
2084 A Study on The Relationship between Building Façade and Solar Energy Utilization Potential in Urban Residential Area in West China

Authors: T. Wen, Y. Liu, J. Wang, W. Zheng, T. Shao

Abstract:

Along with the increasing density of urban population, solar energy potential of building facade in high-density residential areas become a question that needs to be addressed. This paper studies how the solar energy utilization potential of building facades in different locations of a residential areas changes with different building layouts and orientations in Xining, a typical city in west China which possesses large solar radiation resource. Solar energy potential of three typical building layouts of residential areas, which are parallel determinant, gable misalignment, transverse misalignment, are discussed in detail. First of all, through the data collection and statistics of Xining new residential area, the most representative building parameters are extracted, including building layout, building height, building layers, and building shape. Secondly, according to the results of building parameters extraction, a general model is established and analyzed with rhinoceros 6.0 and its own plug-in grasshopper. Finally, results of the various simulations and data analyses are presented in a visualized way. The results show that there are great differences in the solar energy potential of building facades in different locations of residential areas under three typical building layouts. Generally speaking, the solar energy potential of the west peripheral location is the largest, followed by the East peripheral location, and the middle location is the smallest. When the deflection angle is the same, the solar energy potential shows the result that the West deflection is greater than the East deflection. In addition, the optimal building azimuth range under these three typical building layouts is obtained. Within this range, the solar energy potential of the residential area can always maintain a high level. Beyond this range, the solar energy potential drops sharply. Finally, it is found that when the solar energy potential is maximum, the deflection angle is not positive south, but 5 °or 15°south by west. The results of this study can provide decision analysis basis for residential design of Xining city to improve solar energy utilization potential and provide a reference for solar energy utilization design of urban residential buildings in other similar areas.

Keywords: building facade, solar energy potential, solar radiation, urban residential area, visualization, Xining city

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2083 Inflammatory Markers in the Blood and Chronic Periodontitis

Authors: Saimir Heta, Ilma Robo, Nevila Alliu, Tea Meta

Abstract:

Background: Plasma levels of inflammatory markers are the expression of the infectious wastes of existing periodontitis, as well as of existing inflammation everywhere in the body. Materials and Methods: The study consists of the clinical part of the measurement of inflammatory markers of 23 patients diagnosed with chronic periodontitis and the recording of parental periodontal parameters of patient periodontal status: hemorrhage index and probe values, before and 7-10 days after non-surgical periodontal treatment. Results: The level of fibrinogen drops according to the categorization of disease progression, active and passive, with the biggest % (18%-30%) at the fluctuation 10-20 mg/d. Fluctuations in fibrinogen level according to the age of patients in the range 0-10 mg/dL under 40 years and over 40 years was 13%-26%, in the range 10-20 mg/dL was 26%-22%, in the 20-40 mg/dL was 9%-4%. Conclusions: Non-surgical periodontal treatment significantly reduces the level of non-inflammatory markers in the blood. Oral health significantly reduces the potential source for periodontal bacteria, with the potential of promoting thromboembolism, through interaction between thrombocytes.

Keywords: chronic periodontitis, atherosclerosis, risk factor, inflammatory markers

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2082 Blood Flow Simulations to Understand the Role of the Distal Vascular Branches of Carotid Artery in the Stroke Prediction

Authors: Muhsin Kizhisseri, Jorg Schluter, Saleh Gharie

Abstract:

Atherosclerosis is the main reason of stroke, which is one of the deadliest diseases in the world. The carotid artery in the brain is the prominent location for atherosclerotic progression, which hinders the blood flow into the brain. The inclusion of computational fluid dynamics (CFD) into the diagnosis cycle to understand the hemodynamics of the patient-specific carotid artery can give insights into stroke prediction. Realistic outlet boundary conditions are an inevitable part of the numerical simulations, which is one of the major factors in determining the accuracy of the CFD results. The Windkessel model-based outlet boundary conditions can give more realistic characteristics of the distal vascular branches of the carotid artery, such as the resistance to the blood flow and compliance of the distal arterial walls. This study aims to find the most influential distal branches of the carotid artery by using the Windkessel model parameters in the outlet boundary conditions. The parametric study approach to Windkessel model parameters can include the geometrical features of the distal branches, such as radius and length. The incorporation of the variations of the geometrical features of the major distal branches such as the middle cerebral artery, anterior cerebral artery, and ophthalmic artery through the Windkessel model can aid in identifying the most influential distal branch in the carotid artery. The results from this study can help physicians and stroke neurologists to have a more detailed and accurate judgment of the patient's condition.

Keywords: stroke, carotid artery, computational fluid dynamics, patient-specific, Windkessel model, distal vascular branches

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2081 Increase of Sensitivity in 3D Suspended Polymeric Microfluidic Platform through Lateral Misalignment

Authors: Ehsan Yazdanpanah Moghadam, Muthukumaran Packirisamy

Abstract:

In the present study, a design of the suspended polymeric microfluidic platform is introduced that is fabricated with three polymeric layers. Changing the microchannel plane to be perpendicular to microcantilever plane, drastically decreases moment of inertia in that direction. In addition, the platform is made of polymer (around five orders of magnitude less compared to silicon). It causes significant increase in the sensitivity of the cantilever deflection. Next, although the dimensions of this platform are constant, by misaligning the embedded microchannels laterally in the suspended microfluidic platform, the sensitivity can be highly increased. The investigation is studied on four fluids including water, seawater, milk, and blood for flow ranges from low rate of 5 to 70 µl/min to obtain the best design with the highest sensitivity. The best design in this study shows the sensitivity increases around 50% for water, seawater, milk, and blood at the flow rate of 70 µl/min by just misaligning the embedded microchannels in the suspended polymeric microfluidic platform.

Keywords: microfluidic, MEMS, biosensor, microresonator

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2080 Assessing the Quality of Maternity Care in Sub-Saharan Africa Using the Donabedian Quality of Care Framework: A Systematic Scoping Review

Authors: Bernice Boafoaa Gyapong, Anne Jones, Sam Bassett, Janet Anderson

Abstract:

Background: Maternal mortality and morbidity are global concerns, especially in sub-Saharan Africa (SSA). Most maternal mortalities occur at the time of birth. Quality intrapartum care is essential for improving maternal and newborn health outcomes. This scoping review aimed to assess and describe the quality of care during childbirth in SSA to provide an overview of the regional trend of the quality of intrapartum care, the challenges to quality care provision, and identify research gaps. Methods: A scoping review based on Arksey and O’Malley’s scoping review framework was conducted. Medline, CINAHL, PsycINFO, and maternal-infant databases were searched to identify the relevant studies for this review. A narrative summary was presented using themes based on the Donabedian structure, process, and outcome quality of care model. Results: A total of five hundred and forty-seven (547) publications were identified. Fifty-six (56) studies conducted in twenty (20) countries were included in the review. Thirty-four (34) were quantitative, sixteen (16) were qualitative, and six (6) were mixed methods. Most of the studies were related to the process component of quality of care. The provision of emergency obstetric care services, infrastructure, and availability of essential staff and equipment for perinatal care was inadequate in many facilities, particularly rural and peripheral health facilities. Many women experienced disrespectful care during childbirth. Routine care during labour and delivery was observed to be sub-optimal, yet some women reported high satisfaction with care. The use of health facilities for delivery was lower in health centres compared to hospitals. Conclusion: There are variations in the quality of maternity care provided in SSA. Intrapartum care quality is generally deficient in SSA, particularly in peripheral health facilities, health centres, and community clinics. Many of the quality-of-care issues identified are related to the structure component. Stakeholders must develop interventions that comprehensively address these interrelated issues to improve maternal healthcare quality, especially in primary healthcare facilities.

Keywords: quality of care, maternity health, Sub-Saharan Africa, intrapartum

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2079 Copy Number Variants in Children with Non-Syndromic Congenital Heart Diseases from Mexico

Authors: Maria Lopez-Ibarra, Ana Velazquez-Wong, Lucelli Yañez-Gutierrez, Maria Araujo-Solis, Fabio Salamanca-Gomez, Alfonso Mendez-Tenorio, Haydeé Rosas-Vargas

Abstract:

Congenital heart diseases (CHD) are the most common congenital abnormalities. These conditions can occur as both an element of distinct chromosomal malformation syndromes or as non-syndromic forms. Their etiology is not fully understood. Genetic variants such copy number variants have been associated with CHD. The aim of our study was to analyze these genomic variants in peripheral blood from Mexican children diagnosed with non-syndromic CHD. We included 16 children with atrial and ventricular septal defects and 5 healthy subjects without heart malformations as controls. To exclude the most common heart disease-associated syndrome alteration, we performed a fluorescence in situ hybridization test to identify the 22q11.2, responsible for congenital heart abnormalities associated with Di-George Syndrome. Then, a microarray based comparative genomic hybridization was used to identify global copy number variants. The identification of copy number variants resulted from the comparison and analysis between our results and data from main genetic variation databases. We identified copy number variants gain in three chromosomes regions from pediatric patients, 4q13.2 (31.25%), 9q34.3 (25%) and 20q13.33 (50%), where several genes associated with cellular, biosynthetic, and metabolic processes are located, UGT2B15, UGT2B17, SNAPC4, SDCCAG3, PMPCA, INPP6E, C9orf163, NOTCH1, C20orf166, and SLCO4A1. In addition, after a hierarchical cluster analysis based on the fluorescence intensity ratios from the comparative genomic hybridization, two congenital heart disease groups were generated corresponding to children with atrial or ventricular septal defects. Further analysis with a larger sample size is needed to corroborate these copy number variants as possible biomarkers to differentiate between heart abnormalities. Interestingly, the 20q13.33 gain was present in 50% of children with these CHD which could suggest that alterations in both coding and non-coding elements within this chromosomal region may play an important role in distinct heart conditions.

Keywords: aCGH, bioinformatics, congenital heart diseases, copy number variants, fluorescence in situ hybridization

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2078 Identifying the Mindset of Deaf Benildean Students in Learning Anatomy and Physiology

Authors: Joanne Rieta Miranda

Abstract:

Learning anatomy and physiology among Deaf Non-Science major students is a challenge. They have this mindset that Anatomy and Physiology are difficult and very technical. In this study, nine (9) deaf students who are business majors were considered. Non-conventional teaching strategies and classroom activities were employed such as cooperative learning, virtual lab, Facebook live, big sky, blood typing, mind mapping, reflections, etc. Of all the activities; the deaf students ranked cooperative learning as the best learning activity. This is where they played doctors. They measured the pulse rate, heart rate and blood pressure of their partner classmate. In terms of mindset, 2 out of 9 students have a growth mindset with some fixed ideas while 7 have a fixed mindset with some growth ideas. All the students passed the course. Three out of nine students got a grade of 90% and above. The teacher was evaluated by the deaf students as very satisfactory with a mean score of 3.54. This means that the learner-centered practices in the classroom are manifested to a great extent.

Keywords: deaf students, learning anatomy and physiology, teaching strategies, learner-entered practices

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2077 Investigation of Mutagenicity and DNA Binding Properties of Metal-Free and Metallophthalocyanines Containing α-Napththolbenzein Groups on the Peripheral Positions

Authors: Meltem Betül Sağlam, Halil İbrahim Güler, Aykut Sağlam

Abstract:

In this work, phthalocyanine compounds containing α-naphtholbenzeinunits have been synthesized. Mutagenicity and DNA binding properties of the compounds were investigated by Salmonella/Microsome Assay and spectrophotometer. According to the results of the preliminary range finding tests, the compounds gave no toxic effect to all tester strain S. typhimurium TA98 and TA100 at doses of 500, 1100, 350, 500 and 750 µg/plate in the presence and absence of S9, respectively. This study showed that all compounds exhibited efficient DNA-binding activity. In conclusion, these non-toxic compounds may be used as effective DNA dyes for molecular biology studies.

Keywords: dye, mutagenicity, phthalocyanine, toxicity

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2076 Hemato-Biochemical Studies on Naturally Infected Camels with Trypanosomiasis

Authors: Khalid Mehmood, Riaz Hussain, Rao Z. Abbas, Tariq Abbas, Abdul Ghaffar, Ahmad J. Sabir

Abstract:

Blood born diseases such as trypanosomiasis have negative impacts on health, production and working efficiency of camels in different camel-rearing areas of the world including Pakistan. In present study blood samples were collected from camels kept at the desert condition of cholistan to estimate the prevalence of trypanosomiasis and hemato-biochemical changes in naturally infected cases. Results showed an overall 9.31% prevalence of trypanosomiasis in camels. Various clinical signs such as pyrexia, occasional shivering, inappetence, urticaria, swelling, lethargy, going down in condition and edema of pads were observed in few cases. The statistical analysis did not show significant association of age and sex with trypanosomiasis. However, results revealed significantly decreased values of total erythrocyte counts, packed cell volume, hemoglobin concentration, mean corpuscular hemoglobin concentration, serum total proteins and albumin while increased values of mean corpuscular volume was recorded in infected animals as compared to healthy. A significant (P<0.01) increased values of total leukocyte count, monocyte, lymphocyte, neutrophils, and eosinophils was recorded in infected animals. Moreover, microscopic examination of blood films obtained from naturally infected cases showed the presence of parasite and various morphological changes in cells such as stomatocyte, hyperchromasia, and polychromasia. Significantly increased values of different hepatic enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were also recorded.

Keywords: camel, hematological indices, serum enzymes, Trypanosomiasis

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2075 Beneficial Effect of Biotin in Combination with Canagliflozin on High Fat Diet Induced Diabetes in Rats

Authors: Rayhana Begum, HongBin Wang, Nur Alam Siddiquee, Md.Yasin Ahmed

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Biotin treatment has significant effects on blood glucose, and pharmacological doses of biotin improve hyperglycemia. The present study was aimed to investigate the efficacy and safety of biotin in combination with canagliflozin in improving glycemic control on High Fat Diet-induced diabetes in Rats. Thirty male rats were divided into five groups (six rats /group): control, high fat diet (HFD), canagliflozin (CAG), biotin (BIO), and CAG + BIO. The treatments with CAG and /or BIO significantly reduced the body weight gain, blood glucose and HbA1c levels, whereas CAG in combination with BIO revealed greater glycemic improvement than CAG monotherapy. The treatment with CAG and /or BIO causes significant change in lipid profile and CK level while the treatment with CAG in combination with BIO showed better results as compared with CAG monotherapy. Furthermore, combination of biotin with CAG improved the pancreatic and cardiac damage when compared with other treated groups.

Keywords: canagliflozin, biotin, HbA1c, lipid profile

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2074 Exploring the Optimum Temperature and Diet for Growth and Gastric Emptying Time of Juvenile Malabar Blood Snapper (Lutjanus malabaricus)

Authors: Sabuj Kanti Mazumder, Mazlan Abd Ghaffar, Simon Kumar Das

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In this study, we analyzed the effects of water temperature and diet on the growth properties and gastric emptying period of juvenile Malabar blood snapper (Lutjanus malabaricus) over a 30day experimental period. Fish were collected from a local hatchery of Pulau Ketam, Selangor, Malaysia and immediately transferred to flow-through sea water system and subjected to four different temperatures (22, 26, 30, and 34 °C) and two diets (formulated pellet and shrimp). Body weight gain, food consumption, food conversion ratio, food consumption efficiency, specific growth rate, relative growth rate, daily growth rate, and gastric emptying period were significantly influenced by temperature and diet (P<0.05). The best food conversion ratio was with the shrimp group recorded at 30°C (1.33±0.08). The highest growth rate was observed in the shrimp group at 30°C (3.97±0.57% day-1), and the lowest was observed in the formulated pellet group at 22°C (1.63±0.29% day-1). No significant difference was observed between the groups subjected to temperatures of 26 and 30°C. Similarly, the lowest gastric emptying period was detected in the shrimp group at 30°C (16h), where the proportion of meal residues in the stomach decreased from 100% to less than 8% after 12h of starvation. A significantly longer gastric emptying period was observed in the formulated pellet group at 22°C (28h). Overall, the best results were observed on shrimp group subjected to a 30°C temperature. The data obtained from this study suggest that a shrimp diet fed on L. malabaricus at 30°C will optimize the commercial production of this commercially important fish species.

Keywords: aquaculture, diet, digestion rate, growth, Malabar blood snapper

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2073 A 30 Year Audit of the Vascular Complications of Ports: Permanent Intravascular Access Devices

Authors: S. Kershaw, P. J. Barry, K. Webb

Abstract:

Background: Cystic Fibrosis (CF) is a chronic lung disease where patients have chronic lung infection punctuated by acute exacerbations that require intermittent intravenous (IV) antibiotics during their lives. With time, peripheral venous access can become difficult and limited. Accessing these veins can become arduous, traumatic, painful and unworkable. A permanent intravascular access device or Port is a small device that is inserted into the central venous system that allows the delivery of medicine eliminating the need for peripheral venous access. Ports represent a convenient and efficient method when venous access is required on a permanent basis however they are also associated with significant vascular complications. Superior Vena Cava Obstruction (SVCO) is a rare but significant vascular complication of ports in this setting. Objective: We aimed to look at a single CF centre’s experience of port-related SVCO over a thirty year period. Methods: Retrospective data was extracted using patient’s notes, electronic radiological reports and local databases over a period in excess of 30 years from 1982 to 2014. Results: 13 patients were identified with SVCO as a result of their port. 11 patients had CF (9 female, 2 male), one male patient had Primary Ciliary Dyskinesia and one female patient had severe Asthma. The mean port function was 1532 days (range 110 – 4049) and the mean age at SVCO was 24 years (range 11.1 to 36.5 years). The most common symptoms were facial oedema (n=8, 61.5%) and dilated veins (n=6, 46.2%). 7 patients had their Ports removed after SVCO. 6 patients underwent attempted stenting (46.2%) and 6 did not. 4 out of the 6 who underwent stenting required/had re-intervention. 3 of the 6 patients who underwent stenting had symptom resolution, however, 4 of the 6 patients who were not stented had symptom resolution also. Symptom resolution was not guaranteed with stenting and required re-intervention in two-thirds. Conclusion: This case series represents the experience of one of the longest established CF units in the UK and represents the largest cohort ever reported in the literature.

Keywords: ports, Superior Vena Cava Obstruction, cystic fibrosis, access devices

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2072 Leuprolide Induced Scleroderma Renal Crisis: A Case Report

Authors: Nirali Sanghavi, Julia Ash, Amy Wasserman

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Introduction: To the best of our knowledge, there is only one case report that found an association between leuprolide and scleroderma renal crisis (SRC). Leuprolide has been noted to cause acute renal failure in some patients. Given the close timing of the leuprolide injection and the worsening renal function in our patient, leuprolide likely caused exacerbation of lupus nephritis and SRC. Interestingly, our patient on long-term hydroxychloroquine (HCQ) with normal baseline cardiac function was found to have HCQ cardiomyopathy highlighting the need for close monitoring of HCQ toxicity. We know that some of the risk factors that are involved in HCQ induced cardiomyopathy are older age, females, increased dose and >10 years of HCQ use, and pre-existing cardiac and renal insufficiency. Case presentation: A 34-year-old African American woman with a history of overlap of systemic lupus erythematosus (SLE) and scleroderma features and class III lupus nephritis presented with severe headaches, elevated blood pressure (180/120 mmHg) and worsening creatinine levels (2.07 mg/dL). The headaches started 1 month ago after she started leuprolide injections for fibroids. She was being treated with mycophenolate mofetil 1 gm twice a day, belimumab weekly, HCQ 200mg, and prednisone 5 mg daily. She has been on HCQ since her teenage years. The examination was unremarkable except for proximal interphalangeal joint contractures in the right hand and sclerodactyly of bilateral hands, unchanged from baseline. Laboratory findings include urinalysis, which showed 3+ protein, 1+ blood, 6 red blood cells, and 14 white blood cells ruling out thrombotic microangiopathy. C3 was 32 mg/dL, C4 <5 mg/dL, and +dsDNA increased >1000. She was started on captopril and discharged once creatinine and blood pressure was controlled. She was readmitted with hypertension, hyperkalemia, worsening creatinine, nephrotic range proteinuria, complaints of chest pressure, and shortness of breath with pleuritic chest pain. Physical examination and lab findings were unchanged. She was treated with pulse dose methyl prednisone followed by taper and multiple anti-hypertensive agents, including captopril, for presumed lupus nephritis flare versus SRC. Renal biopsy was consistent with SRC and class IV lupus nephritis and was started on cyclophosphamide. While cardiac biopsy showed borderline myocarditis without necrosis and cytoplasmic vacuolization consistent with HCQ cardiomyopathy, hence HCQ was discontinued. Summary: It highlights a rare association of leuprolide causing exacerbation of lupus nephritis or SRC. Although rare, the current case reinforces the importance of close monitoring for HCQ toxicity in patients with renal insufficiency.

Keywords: leuprolide, lupus nephritis, scleroderma, SLE

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2071 Sympathetic Skin Response and Reaction Times in Chronic Autoimmune Thyroiditis; An Overlooked Electrodiagnostic Study

Authors: Oya Umit Yemisci, Nur Saracgil Cosar, Tubanur Ozturk Sisman, Selin Ozen

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Chronic autoimmune thyroiditis (AIT) may result in a wide spectrum of reversible abnormalities in the neuromuscular function. Usually, proximal muscle-related symptoms and neuropathic findings such as mild axonal peripheral neuropathy have been reported. Sympathetic skin responses are useful in evaluating sudomotor activity of the unmyelinated sympathetic fibers of the autonomic nervous system. Neurocognitive impairment may also be a prominent feature of hypothyroidism, particularly in elderly patients. Electromyographic reaction times as a highly sensitive parameter provides. Objective data concerning cognitive and motor functions. The aim of this study was to evaluate peripheral nerve functions, sympathetic skin response and electroneuromyographic (ENMG) reaction times in euthyroid and subclinically hypothyroid patients with a diagnosis of AIT and compare to those of a control group. Thirty-five euthyroid, 19 patients with subclinical hypothyroidism and 35 age and sex-matched healthy subjects were included in the study. Motor and sensory nerve conduction studies, sympathetic skin responses recorded from hand and foot by stimulating contralateral median nerve and simple reaction times by stimulating tibial nerve and recording from extensor indicis proprius muscle were performed to all patients and control group. Only median nerve sensory conduction velocities of the forearm were slower in patients with AIT compared to the control group (p=0.019). Otherwise, nerve conduction studies and sympathetic skin responses showed no significant difference between the patients and the control group. However, reaction times were shorter in the healthy subjects compared to AIT patients. Prolongation in the reaction times may be considered as a parameter reflecting the alterations in the cognitive functions related to the primary disease process in AIT. Combining sympathetic skin responses with more quantitative tests such as cardiovascular tests and sudomotor axon reflex testing may allow us to determine higher rates of involvement of the autonomic nervous system in AIT.

Keywords: sympathetic skin response, simple reaction time, chronic autoimmune thyroiditis

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2070 Study of Mixing Conditions for Different Endothelial Dysfunction in Arteriosclerosis

Authors: Sara Segura, Diego Nuñez, Miryam Villamil

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In this work, we studied the microscale interaction of foreign substances with blood inside an artificial transparent artery system that represents medium and small muscular arteries. This artery system had channels ranging from 75 μm to 930 μm and was fabricated using glass and transparent polymer blends like Phenylbis(2,4,6-trimethylbenzoyl) phosphine oxide, Poly(ethylene glycol) and PDMS in order to be monitored in real time. The setup was performed using a computer controlled precision micropump and a high resolution optical microscope capable of tracking fluids at fast capture. Observation and analysis were performed using a real time software that reconstructs the fluid dynamics determining the flux velocity, injection dependency, turbulence and rheology. All experiments were carried out with fully computer controlled equipment. Interactions between substances like water, serum (0.9% sodium chloride and electrolyte with a ratio of 4 ppm) and blood cells were studied at microscale as high as 400nm of resolution and the analysis was performed using a frame-by-frame observation and HD-video capture. These observations lead us to understand the fluid and mixing behavior of the interest substance in the blood stream and to shed a light on the use of implantable devices for drug delivery at arteries with different Endothelial dysfunction. Several substances were tested using the artificial artery system. Initially, Milli-Q water was used as a control substance for the study of the basic fluid dynamics of the artificial artery system. However, serum and other low viscous substances were pumped into the system with the presence of other liquids to study the mixing profiles and behaviors. Finally, mammal blood was used for the final test while serum was injected. Different flow conditions, pumping rates, and time rates were evaluated for the determination of the optimal mixing conditions. Our results suggested the use of a very fine controlled microinjection for better mixing profiles with and approximately rate of 135.000 μm3/s for the administration of drugs inside arteries.

Keywords: artificial artery, drug delivery, microfluidics dynamics, arteriosclerosis

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2069 Reduced Glycaemic Impact by Kiwifruit-Based Carbohydrate Exchanges Depends on Both Available Carbohydrate and Non-Digestible Fruit Residue

Authors: S. Mishra, J. Monro, H. Edwards, J. Podd

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When a fruit such as kiwifruit is consumed its tissues are released from the physical /anatomical constraints existing in the fruit. During digestion they may expand several-fold to achieve a hydrated solids volume far greater than the original fruit, and occupy the available space in the gut, where they surround and interact with other food components. Within the cell wall dispersion, in vitro digestion of co-consumed carbohydrate, diffusion of digestion products, and mixing responsible for mass transfer of nutrients to the gut wall for absorption, were all retarded. All of the foregoing processes may be involved in the glycaemic response to carbohydrate foods consumed with kiwifruit, such as breakfast cereal. To examine their combined role in reducing the glycaemic response to wheat cereal consumed with kiwifruit we formulated diets containing equal amounts of breakfast cereal, with the addition of either kiwifruit, or sugars of the same composition and quantity as in kiwifruit. Therefore, the only difference between the diets was the presence of non-digestible fruit residues. The diet containing the entire disperse kiwifruit significantly reduced the glycaemic response amplitude and the area under the 0-120 min incremental blood glucose response curve (IAUC), compared with the equicarbohydrate diet containing the added kiwifruit sugars. It also slightly but significantly increased the 120-180 min IAUC by preventing a postprandial overcompensation, indicating improved homeostatic blood glucose control. In a subsequent study in which we used kiwifruit in a carbohydrate exchange format, in which the kiwifruit carbohydrate partially replaced breakfast cereal in equal carbohydrate meals, the blood glucose was further reduced without a loss of satiety, and with a reduction in insulin demand. The results show that kiwifruit may be a valuable component in low glycaemic impact diets.

Keywords: carbohydrate, digestion, glycaemic response, kiwifruit

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2068 Comprehensive Ultrasonography During Low-flow Bypass in Patients with Symptomatic Internal Carotid Artery (ICA) Occlusion

Authors: G. K. Guseynova, V. V. Krylov, L. T. Khamidova, N. A. Polunina, V. A. Lukyanchikov

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The report presents complex ultrasound diagnostics in patients with symptomatic steno-occlusive lesions of extra- and intracranial branches of brachiocephalic arteries (BCA). The tasks and possibilities of ultrasound diagnostics at different stages of treatment of patients with symptomatic occlusion of internal carotid artery (ICA) are covered in detail; qualitative and quantitative characteristics of blood flow; parameters of the wall and lumen of the main arteries of the head; methods of ultrasound examination of indirect assessment of the functional status are presented. Special attention is paid to the description of indicators that are predictors of the consistency of formed extra-intracranial low-flow shunts, examples of functioning and failed anastomoses are analyzed.

Keywords: CBF, cerebral blood flow; CTA, external carotid artery; ICA, internal carotid artery; MCA, middle cerebral artery; MRA, magnetic resonance angiography; OEF, oxygen extraction fraction; TIA, transient ischaemic attack, ultrasound, low-flow bypass, anastomoses

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2067 Diabetes Mellitus and Blood Glucose Variability Increases the 30-day Readmission Rate after Kidney Transplantation

Authors: Harini Chakkera

Abstract:

Background: Inpatient hyperglycemia is an established independent risk factor among several patient cohorts with hospital readmission. This has not been studied after kidney transplantation. Nearly one-third of patients who have undergone a kidney transplant reportedly experience 30-day readmission. Methods: Data on first-time solitary kidney transplantations were retrieved between September 2015 to December 2018. Information was linked to the electronic health record to determine a diagnosis of diabetes mellitus and extract glucometeric and insulin therapy data. Univariate logistic regression analysis and the XGBoost algorithm were used to predict 30-day readmission. We report the average performance of the models on the testing set on five bootstrapped partitions of the data to ensure statistical significance. Results: The cohort included 1036 patients who received kidney transplantation, and 224 (22%) experienced 30-day readmission. The machine learning algorithm was able to predict 30-day readmission with an average AUC of 77.3% (95% CI 75.30-79.3%). We observed statistically significant differences in the presence of pretransplant diabetes, inpatient-hyperglycemia, inpatient-hypoglycemia, and minimum and maximum glucose values among those with higher 30-day readmission rates. The XGBoost model identified the index admission length of stay, presence of hyper- and hypoglycemia and recipient and donor BMI values as the most predictive risk factors of 30-day readmission. Additionally, significant variations in the therapeutic management of blood glucose by providers were observed. Conclusions: Suboptimal glucose metrics during hospitalization after kidney transplantation is associated with an increased risk for 30-day hospital readmission. Optimizing the hospital blood glucose management, a modifiable factor, after kidney transplantation may reduce the risk of 30-day readmission.

Keywords: kidney, transplant, diabetes, insulin

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2066 Lack of Association between IL-10 Promoter Gene Polymorphisms and Tuberculosis Susceptibility in Thai Population

Authors: Manaphol Kulpraneet, Anirut Limtrakul, Surangrat Srisurapanon, Piyatida Tangteerawatana

Abstract:

Tuberculosis (TB) remains a global health care disease world-wide. Control of the global TB epidemic has been impaired by the lack of an effective vaccine, by the emergence of drug resistant forms of Mycobacterium tuberculosis and by lack of sensitive and rapid diagnostics. Cytokines play a major role in defense against M. tuberculosis infection. Polymorphisms in the genes encoding various cytokines have been associated with tuberculosis susceptibility. Polymorphisms of the regulatory cytokine gene, the interleukin (IL)-10 is associated with the risk of tuberculosis (TB) in different populations. However, IL-10 gene polymorphism and susceptibility to TB in Thai is still unknown. The purpose of this study was to evaluate whether the common IL-10 promoter gene polymorphisms are associated with TB in Thai population. Forty eight patients with newly diagnosed pulmonary tuberculosis were studied. DNA samples were extracted from leukocytes and used to investigate -1087A/G, -819C/T, -252C/A (rs1800896, rs1800871, rs1800872) in IL-10 gene using restriction fragment length polymorphism (PCR-RFLP) methods. In this study, the genotype and allele frequencies of IL-10-1087A/G, -819C/T, -252C/A polymorphism did not significantly different between TB patients and healthy controls ((genotype: p=0.38, p=0.92, p=1; allele: p=0.57, p=0.77, p=0.89, respectively). The lack of association between common IL-10 promoter polymorphisms and TB susceptibility in this study may provide clue for better understanding of IL-10-1087A/G, -819C/T, -252C/A polymorphism and TB susceptibility in Thai population, which might facilitate the rationale design of vaccines. However, further studies in large scales population are required for confirmation.

Keywords: IL-10, cytokines, single nucleotide polymorphism (SNP), tuberculosis

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2065 Bacteremia Caused by Nontoxigenic Vibrio cholerae in an Immunocompromised Patient in Istanbul, Turkey

Authors: Fatma Koksal Çakirlar, Si̇nem Ozdemir, Selcan Akyol, Revazi̇ye Gulesen, Murat Gunaydin, Nevri̇ye Gonullu, Belkis Levent, Nuri̇ Kiraz

Abstract:

Vibrio cholerae O1 and O139 are the causative agent of epidemic or pandemic cholera. V. cholerae O1 is generally accepted as a non-invasive enterotoxigenic organism causing gastroenteritis of various severities. Non-O1 V. cholerae can cause small outbreaks of diarrhea due to consumption of contaminated food and water. Particularly, the patients with achlorydria have a risk for vibrio infections. There are numerous case reports of bacteremia caused by vibrio in patients with predisposing conditions like cirrhosis, nephrotic syndrome, diabetes, hematologic malignancy, gastrectomy, and AIDS. We described in this study the first case of nontoxigenic, non-01/non-O139 V. cholerae isolated from the blood culture of a 77-year-old female patient with hipertension, diabetes, coronary artery disease, gout and about 9 years ago migrated breast cancer history. The patient with complaints of shortness of breath, fever and malaise admitted to our emergency clinic were evaluated. There was no diarrhea or abdominal symptoms in the patient. No growth in her urine culture, but blood culture (BACTEC 9120 system, Becton Dickinson, USA) was positive for non-01/non-O139 V. cholerae that was identified by conventional methods and Phoenix automated system (BD Diagnostic Systems, Sparks, MD). It does not secrete the cholera toxin. The agglutination test was negative with polyvalent O1 antisera and O139 antiserum. Empirically ceftriaxone was administered to the patient and she was discharged with improvement in general condition. In this study we report bacteremia by non-01/non-O139 V. cholerae that is rare in the worldwide and first in Turkey.

Keywords: bacteremia, blood culture, immunocompromised patient, Non-O1 vibrio cholerae

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2064 Long-Term Cohort of Patients with Beta Thalassemia; Prevailing Role of Serum Ferritin Levels in Hypocalcemia and Growth Retardation

Authors: Shervin Rashidinia, Sara Shahmoradi, Seyyed Shahin Eftekhari, Mohsen Talebizadeh, Mohammad Saleh Sadeghi

Abstract:

Background: Beta-thalassemia Major (BTM) is a kind of hereditary hemolytic anemia which depended on regular monthly blood transfusion. However, iron deposition into the organs leads to multi-organ damage. The present study is the first study which aimed to evaluate the average of five-years serum ferritin level and compared by the prevalence of short stature and hypocalcemia. Materials/Methods: A cross-sectional retrospective study which a total of 140 patients with beta-thalassemia who were referred to Qom Thalassemia Clinic between February 2011 and July 2016 were enrolled to be reviewed. The exclusion criteria were consisting of incomplete medical records, diagnosis less than 2-years-ago and the blood transfusion less than every 4 weeks. The data including age, gender, weight, height, age of initial blood transfusion, age of initial chelation therapy, ferritin, and calcium were collected and analysis by SPSS version 24. Results: A total of 140 patients were enrolled. Of them, 75 (53.4%) were female. The mean age of the patients was 13.4±4.6 years.The mean age of initial diagnosis was 20.2±7.4 months. Hypocalcemia and short stature were occurred in 41 (29.3%) and 37 (26.4%) patients, respectively. The mean five-years serum ferritin level was significantly higher in the patients with short stature and hypocalcemia (P<0.0001). However, rise in serum ferritin level significantly increases the risk of short-stature and hypocalcemia (1.0004- and 1.0029 fold, respectively). Conclusion: We demonstrated that prevalence of short stature and hypocalcemia were significantly higher in the BTM.However, ferritin significantly increases the risk of short stature and hypocalcemia.

Keywords: beta-thalassemia, ferritin, growth retardation, hypocalcemia

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2063 Hemodynamics of a Cerebral Aneurysm under Rest and Exercise Conditions

Authors: Shivam Patel, Abdullah Y. Usmani

Abstract:

Physiological flow under rest and exercise conditions in patient-specific cerebral aneurysm models is numerically investigated. A finite-volume based code with BiCGStab as the linear equation solver is used to simulate unsteady three-dimensional flow field through the incompressible Navier-Stokes equations. Flow characteristics are first established in a healthy cerebral artery for both physiological conditions. The effect of saccular aneurysm on cerebral hemodynamics is then explored through a comparative analysis of the velocity distribution, nature of flow patterns, wall pressure and wall shear stress (WSS) against the reference configuration. The efficacy of coil embolization as a potential strategy of surgical intervention is also examined by modelling coil as a homogeneous and isotropic porous medium where the extended Darcy’s law, including Forchheimer and Brinkman terms, is applicable. The Carreau-Yasuda non-Newtonian blood model is incorporated to capture the shear thinning behavior of blood. Rest and exercise conditions correspond to normotensive and hypertensive blood pressures respectively. The results indicate that the fluid impingement on the outer wall of the arterial bend leads to abnormality in the distribution of wall pressure and WSS, which is expected to be the primary cause of the localized aneurysm. Exercise correlates with elevated flow velocity, vortex strength, wall pressure and WSS inside the aneurysm sac. With the insertion of coils in the aneurysm cavity, the flow bypasses the dilatation, leading to a decline in flow velocities and WSS. Particle residence time is observed to be lower under exercise conditions, a factor favorable for arresting plaque deposition and combating atherosclerosis.

Keywords: 3D FVM, Cerebral aneurysm, hypertension, coil embolization, non-Newtonian fluid

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2062 Design and Fabrication of Micro-Bubble Oxygenator

Authors: Chiang-Ho Cheng, An-Shik Yang, Hong-Yih Cheng

Abstract:

This paper applies the MEMS technology to design and fabricate a micro-bubble generator by a piezoelectric actuator. Coupled with a nickel nozzle plate, an annular piezoelectric ceramic was utilized as the primary structure of the generator. In operations, the piezoelectric element deforms transversely under an electric field applied across the thickness of the generator. The surface of the nozzle plate can expand or contract because of the induction of radial strain, resulting in the whole structure to bend, and successively transport oxygen micro-bubbles into the blood flow for enhancing the oxygen content in blood. In the tests, a high magnification microscope and a high speed CCD camera were employed to photograph the time evolution of meniscus shape of gaseous bubbles dispensed from the micro-bubble generator for flow visualization. This investigation thus explored the bubble formation process including the influences of inlet gas pressure along with driving voltage and resonance frequency on the formed bubble extent.

Keywords: micro-bubble, oxygenator, nozzle, piezoelectric

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2061 The Study of Platelet-Rich Plasma(PRP) on Wounds of OLEFT Rats Using Expression of MMP-2, MMP-9 mRNA

Authors: Ho Seong Shin

Abstract:

Introduction: A research in relation to wound healing also showed that platelet-rich plasma (PRP) was effective on normal tissue regeneration. Nonetheless, there is no evidence that when platelet-rich plasma was applied on diabetic wound, it normalize diabetic wound healing process. In this study, we have analyzed matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) expression to know the effect of PRP on diabetic wounds using Reverse transcription-polymerase chain reaction (RT-PCR) of MMP-2, MMP-9 mRNA. Materials and Methods: Platelet-rich plasma (PRP) was prepared from blood of 6 rats. The whole 120-mL was added immediately to an anticoagulant. Citrate phosphonate dextrose(CPD) buffer (0.15 mg CPDmL) in a ratio of 1 mL of CPD buffer to 5 mL of blood. The blood was then centrifuged at 220g for 20minutes. The supernatant was saved to produce fibrin glue. The participate containing PRP was used for second centrifugation at 480g for 20 minutes. The pellet from the second centrifugation was saved and diluted with supernatant until the platelet concentration became 900,000/μL. Twenty male, 4week-old OLETF rats were underwent operation; each rat had two wounds created on left and right sides. The each wound of left side was treated with PRP gel, the wound of right side was treated with physiologic saline gauze. Results: RT-PCR analysis; The levels of MMP-2 mRNA in PRP applied tissues were positively related to postwounding days, whereas MMP-2 mRNA expression in saline-applied tissues remained in 5day after treatment. MMP-9 mRNA was undetectable in saline-applied tissues for either tissue, except 3day after treatment. Following PRP-applied tissues, MMP-9 mRNA expression was detected, with maximal expression being seen at third day. The levels of MMP-9 mRNA in PRP applied tissues were reported high intensity of optical density related to saline applied tissues.

Keywords: diabetes, MMP-2, MMP-9, OLETF, PRP, wound healing MMP-9

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2060 Community Engagement Strategies to Assist with the Development of an RCT Among People Living with HIV

Authors: Joyce K. Anastasi, Bernadette Capili

Abstract:

Community Engagement Strategies to Assist with the Development of an RCT Among People Living with HIV Our research team focuses on developing and testing protocols to manage chronic symptoms. For many years, our team designed and implemented symptom management studies for people living with HIV (PLWH). We identify symptoms that are not curative and are not adequately controlled by conventional therapies. As an exemplar, we describe how we successfully engaged PLWH in developing and refining our research feasibility protocol for distal sensory peripheral neuropathy (DSP) associated with HIV. With input from PLWH with DSP, our research received National Institutes of Health (NIH) research funding support. Significance: DSP is one of the most common neurologic complications in HIV. It is estimated that DSP affects 21% to 50% of PLWH. The pathogenesis of DSP in HIV is complex and unclear. Proposed mechanisms include cytokine dysregulation, viral protein-produced neurotoxicity, and mitochondrial dysfunction associated with antiretroviral medications. There are no FDA-approved treatments for DSP in HIV. Purpose: Aims: 1) to explore the impact of DSP on the lives of PLWH, 2) to identify patients’ perspectives on successful treatments for DSP, 3) to identify interventions considered feasible and sensitive to the needs of PLWH with DSP, and 4) to obtain participant input for protocol/study design. Description of Process: We conducted a needs assessment with PLWH with DSP. From our needs assessment, we learned from the patients’ perspective detailed descriptions of their symptoms; physical functioning with DSP; self-care remedies tried, and desired interventions. We also asked about protocol scheduling, instrument clarity, study compensation, study-related burdens, and willingness to participate in a randomized controlled trial (RCT) with a placebo and a waitlist group. Implications: We incorporated many of the suggestions learned from the need assessment. We developed and completed a feasibility study that provided us with invaluable information that informed subsequent NIH-funded studies. In addition to our extensive clinical and research experience working with PLWH, learning from the patient perspective helped in developing our protocol and promoting a successful plan for recruitment and retention of study participants.

Keywords: clinical trial development, peripheral neuropathy, traditional medicine, HIV, AIDS

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2059 The Effect of Acute Muscular Exercise and Training Status on Haematological Indices in Adult Males

Authors: Ibrahim Musa, Mohammed Abdul-Aziz Mabrouk, Yusuf Tanko

Abstract:

Introduction: Long term physical training affect the performance of athletes especially the females. Soccer which is a team sport, played in an outdoor field, require adequate oxygen transport system for the maximal aerobic power during exercise in order to complete 90 minutes of competitive play. Suboptimal haematological status has often been recorded in athletes with intensive physical activity. It may be due to the iron depletion caused by hemolysis or haemodilution results from plasma volume expansion. There is lack of data regarding the dynamics of red blood cell variables, in male football players. We hypothesized that, a long competitive season involving frequent matches and intense training could influence red blood cell variables, as a consequence of applying repeated physical loads when compared with sedentary. Methods: This cross sectional study was carried on 40 adult males (20 athletes and 20 non athletes) between 18-25 years of age. The 20 apparently healthy male non athletes were taken as sedentary and 20 male footballers comprise the study group. The university institutional review board (ABUTH/HREC/TRG/36) gave approval for all procedures in accordance with the Declaration of Helsinki. Red blood cell (RBC) concentration, packed cell volume (PCV), and plasma volume were measured in fasting state and immediately after exercise. Statistical analysis was done by using SPSS/ win.20.0 for comparison within and between the groups, using student’s paired and unpaired “t” test respectively. Results: The finding from our study shows that, immediately after termination of exercise, the mean RBC counts and PCV significantly (p<0.005) decreased with significant increased (p<0.005) in plasma volume when compared with pre-exercised values in both group. In addition the post exercise RBC was significantly higher in untrained (261.10±8.5) when compared with trained (255.20±4.5). However, there was no significant differences in the post exercise hematocrit and plasma volume parameters between the sedentary and the footballers. Moreover, beside changes in pre-exercise values among the sedentary and the football players, the resting red blood cell counts and Plasma volume (PV %) was significantly (p < 0.05) higher in the sedentary group (306.30±10.05 x 104 /mm3; 58.40±0.54%) when compared with football players (293.70±4.65 x 104 /mm3; 55.60±1.18%). On the other hand, the sedentary group exhibited significant (p < 0.05) decrease in PCV (41.60±0.54%) when compared with the football players (44.40±1.18%). Conclusions: It is therefore proposed that the acute football exercise induced reduction in RBC and PCV is entirely due to plasma volume expansion, and not of red blood cell hemolysis. In addition, the training status also influenced haematological indices of male football players differently from the sedentary at rest due to adaptive response. This is novel.

Keywords: Haematological Indices, Performance Status, Sedentary, Male Football Players

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2058 A Brief Review on Doping in Sports and Performance-Enhancing Drugs

Authors: Zahra Mohajer, Afsaneh Soltani

Abstract:

Doping is a major issue in competitive sports and is favored by vast groups of athletes. The feeling of being higher-ranking than others and gaining fame has caused many athletes to misuse drugs. The definition of doping is to use prohibited substances and/or methods that help physical or mental performances or both. Doping counts as the illegal use of chemical substances or drugs, excessive amounts of physiological substances to increase the performance at or out of competition or even the use of inappropriate medications to treat an injury to gain the ability to participate in a competition. The International Olympic Committee (IOC) and World Anti-Doping Agency (WADA) have forbidden these substances to ensure fair and equal competition and also the health of the competitors. As of 2004 WADA has published an international list of illegal substances used for doping, which is updated annually. In the process of the Genome Project scientists have gained the ability to treat numerous diseases by gene therapy, which may result in bodily performance increase and therefore a potential opportunity to misuse by some athletes. Gene doping is defined as the non-therapeutic direct and indirect genetic modifications using genetic materials that can improve the performances in sports events. Biosynthetic drugs are a form of indirect genetic engineering. The method can be performed in three ways such as injecting the DNA directly into the muscle, inserting the genetically engineered cells, or transferring the DNA using a virus as a vector. Erythropoietin is a hormone majorly released by the kidney and in small amounts by the liver. Its function is to stimulate the erythropoiesis and therefore the more production of red blood cells (RBC) which causes an increase in Hemoglobin (Hb). During this process, the oxygen delivery to muscles will increase, which will improve athletic performance and postpone exhaustion. There are ways to increase the oxygen transferred to muscles such as blood transfusion, stimulating the production of red blood cells by using Erythropoietin (EPO), and also using allosteric effectors of Hemoglobin. EPO can either be injected as a protein or can be inserted into the cells as the gene which encodes EPO. Adeno-associated viruses have been employed to deliver the EPO gene to the cells. Employing the genes that naturally exist in the human body such as the EPO gene can reduce the risk of detecting gene doping. The first research about blood doping was conducted in 1947. The study has shown that an increase in hematocrit (HCT) up to 55% following homologous transfusion makes it more unchallenging for the body to perform the exercise at the altitude. Thereafter athletes’ attraction to blood infusion escalated. Also, a study has demonstrated that by reinfusing their own blood 4 weeks after being drawn, three men have shown a rise in Hb level which improved the oxygen uptake, and a delay in exhaustion. The list of performance-enhancing drugs is published by WADA annually and includes the following drugs: anabolic agents, hormones, Beta-2 agonists, Beta-blockers, Diuretics, Stimulants, narcotics, cannabinoids, and corticosteroids.

Keywords: doping, PEDs, sports, WADA

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2057 The Second Generation of Tyrosine Kinase Inhibitor Afatinib Controls Inflammation by Regulating NLRP3 Inflammasome Activation

Authors: Shujun Xie, Shirong Zhang, Shenglin Ma

Abstract:

Background: Chronic inflammation might lead to many malignancies, and inadequate resolution could play a crucial role in tumor invasion, progression, and metastases. A randomised, double-blind, placebo-controlled trial shows that IL-1β inhibition with canakinumab could reduce incident lung cancer and lung cancer mortality in patients with atherosclerosis. The process and secretion of proinflammatory cytokine IL-1β are controlled by the inflammasome. Here we showed the correlation of the innate immune system and afatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer. Methods: Murine Bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMs) and THP-1 were used to check the effect of afatinib on the activation of NLRP3 inflammasome. The assembly of NLRP3 inflammasome was check by co-immunoprecipitation of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), disuccinimidyl suberate (DSS)-cross link of ASC. Lipopolysaccharide (LPS)-induced sepsis and Alum-induced peritonitis were conducted to confirm that afatinib could inhibit the activation of NLRP3 in vivo. Peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) patients before or after taking afatinib were used to check that afatinib inhibits inflammation in NSCLC therapy. Results: Our data showed that afatinib could inhibit the secretion of IL-1β in a dose-dependent manner in macrophage. Moreover, afatinib could inhibit the maturation of IL-1β and caspase-1 without affecting the precursors of IL-1β and caspase-1. Next, we found that afatinib could block the assembly of NLRP3 inflammasome and the ASC speck by blocking the interaction of the sensor protein NLRP3 and the adaptor protein ASC. We also found that afatinib was able to alleviate the LPS-induced sepsis in vivo. Conclusion: Our study found that afatinib could inhibit the activation of NLRP3 inflammasome in macrophage, providing new evidence that afatinib could target the innate immune system to control chronic inflammation. These investigations will provide significant experimental evidence in afatinib as therapeutic drug for non-small cell lung cancer or other tumors and NLRP3-related diseases and will explore new targets for afatinib.

Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor

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