Search results for: geriatric medicine

Authors: Alua Massalimova

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Situation analysis of Blood Service revealed that the strengths dominated over the weak 1.4 times. The possibilities dominate over the threats by 1.1 times. It follows that by using timely the possibility the Service, it is possible to strengthen its strengths and avoid threats. Priority directions of the resulting analysis are the use of subjective factors, such as personal management capacity managers of the Blood Center in the field of possibilities of legal activity of administrative decisions and the mobilization of stable staff in general market conditions. We have studied for the period 2011-2015 retrospectively indicators of Blood Service of Kazakhstan. Strengths of Blood Service of RK(Ps4,5): 1) indicators of donations for 1000 people is higher than in some countries of the CIS (in Russia 14, Kazakhstan - 17); 2) the functioning science centre of transfusiology; 3) the legal possibility of additional financing blood centers in the form of paid services; 4) the absence of competitors; 5) training on specialty Transfusiology; 6) the stable management staff of blood centers, a high level of competence; 7) increase in the incidence requiring transfusion therapy (oncohematology); 8) equipment upgrades; 9) the opening of a reference laboratory; 10) growth of the proportion of issued high-quality blood components; 11) governmental organization 'Drop of Life'; 12) the functioning bone marrow register; 13) equipped with modern equipment HLA-laboratory; 14) High categorization of average medical workers; 15) availability of own specialized scientific journal; 16) vivarium. The weaknesses (Ps = 3.5): 1) the incomplete equipping of blood centers and blood transfusion cabinets according to standards; 2) low specific weight of paid services of the CC; 3) low categorization of doctors; 4) high staff turnover; 5) the low scientific potential of industrial and clinical of transfusiology; 6) the low wages paid; 7) slight growth of harvested donor blood; 8) the weak continuity with offices blood transfusion; 9) lack of agitation work; 10) the formally functioning of Transfusion Association; 11) the absence of scientific laboratories; 12) high standard deviation from the average for donations in the republic. The possibilities (Ps = 2,7): 1): international grants; 2) organization of international seminars on clinical of transfusiology; 3) cross-sectoral cooperation; 4) to increase scientific research in the field of clinical of transfusiology; 5) reduce the share of donation unsuitable for transfusion and processing; 6) strengthening marketing management in the development of fee-based services; 7) advertising paid services; 8) strengthening the publishing of teaching aids; 9) team-building staff. The threats (Ps = 2.1): 1) an increase of staff turnover; 2) the risk of litigation; 3) reduction gemoprodukts based on evidence-based medicine; 4) regression of scientific capacity; 5) organization of marketing; 6) transfusiologist marketing; 7) reduction in the quality of the evidence base transfusions.

Keywords: blood service, healthcare, Kazakhstan, quantative swot analysis

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Authors: Orkide Donma, Mustafa M. Donma

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Childhood obesity, which may lead to increased risk for heart diseases in children as well as adults, is one of the most important health problems throughout the world. Prevalences of morbid obesity and metabolic syndrome (MetS) are being increased during childhood age group. MetS is a cluster of metabolic and vascular abnormalities including hypercoagulability and an increased risk of cardiovascular diseases (CVDs). There are also some relations between some components of MetS and leukocytes. The aim of this study is to investigate complete blood cell count parameters that differ between morbidly obese boys and girls with MetS diagnosis. A total of 117 morbid obese children with MetS consulted to Department of Pediatrics in Faculty of Medicine Hospital at Namik Kemal University were included into the scope of the study. The study population was classified based upon their genders (60 girls and 57 boys). Their heights and weights were measured and body mass index (BMI) values were calculated. WHO BMI-for age and sex percentiles were used. The values above 99 percentile were defined as morbid obesity. Anthropometric measurements were performed. Waist-to-hip and head-to-neck ratios as well as homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. Components of MetS (central obesity, glucose intolerance, high blood pressure, high triacylglycerol levels, low levels of high density lipoprotein cholesterol) were determined. Hematological variables were measured. Statistical analyses were performed using SPSS. The degree for statistical significance was p ≤ 0.05. There was no statistically significant difference between the ages (11.2±2.6 years vs 11.2±3.0 years) and BMIs (28.6±5.2 kg/m² vs 29.3±5.2 kg/m²) of boys and girls (p ≥ 0.05), respectively. Significantly increased waist-to-hip ratios were obtained for boys (0.94±0.08 vs 0.91±0.06; p=0.023). Significantly elevated values of hemoglobin (13.55±0.98 vs 13.06±0.82; p=0.004), mean corpuscular hemoglobin concentration (33.79±0.91 vs 33.21±1.14; p=0.003), eosinophils (0.300±0.253 vs 0.196±0.197; p=0.014), and platelet (347.1±81.7 vs 319.0±65.9; p=0.042) were detected for boys. There was no statistically significant difference between the groups in terms of neutrophil/lymphocyte ratios as well as HOMA-IR values (p ≥ 0.05). Statistically significant gender-based differences were found for hemoglobin as well as mean corpuscular hemoglobin concentration and hence, separate reference intervals for two genders should be considered for these parameters. Eosinophils may contribute to the development of thrombus in acute coronary syndrome. Eosinophils are also known to make an important contribution to mechanisms related to thrombosis pathogenesis in acute myocardial infarction. Increased platelet activity is observed in patients with MetS and these individuals are more susceptible to CVDs. In our study, elevated platelets described as dominant contributors to hypercoagulability and elevated eosinophil counts suggested to be related to the development of CVDs observed in boys may be the early indicators of the future cardiometabolic complications in this gender.

Keywords: children, complete blood count, gender, metabolic syndrome

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Authors: Anthony S. Machi, Joseph Minardi

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We present a case report of left atrial myxoma diagnosed by bedside transesophageal (TEE) ultrasound. Left atrial myxoma is the most common benign cardiac tumor and can obstruct blood flow and cause valvular insufficiency. Common symptoms consist of dyspnea, pulmonary edema and other features of left heart failure in addition to thrombus release in the form of tumor fragments. The availability of bedside ultrasound equipment is essential for the quick diagnosis and treatment of various emergency conditions including cardiac neoplasms. A 48-year-old Caucasian female with a four-year history of an untreated renal mass and anemia presented to the ED with two months of sharp, intermittent, bilateral flank pain radiating into the abdomen. She also reported intermittent vomiting and constipation along with generalized body aches, night sweats, and 100-pound weight loss over last year. She had a CT in 2013 showing a 3 cm left renal mass and a second CT in April 2016 showing a 3.8 cm left renal mass along with a past medical history of diverticulosis, chronic bronchitis, dyspnea on exertion, uncontrolled hypertension, and hyperlipidemia. Her maternal family history is positive for breast cancer, hypertension, and Type II Diabetes. Her paternal family history is positive for stroke. She was a current everyday smoker with an 11 pack/year history. Alcohol and drug use were denied. Physical exam was notable for a Grade II/IV systolic murmur at the right upper sternal border, dyspnea on exertion without angina, and a tender left lower quadrant. Her vitals and labs were notable for a blood pressure of 144/96, heart rate of 96 beats per minute, pulse oximetry of 96%, hemoglobin of 7.6 g/dL, hypokalemia, hypochloremia, and multiple other abnormalities. Physicians ordered a CT to evaluate her flank pain which revealed a 7.2 x 8.9 x 10.5 cm mixed cystic/solid mass in the lower pole of the left kidney and a filling defect in the left atrium. Bedside TEE was ordered to follow up on the filling defect. TEE reported an ejection fraction of 60-65% and visualized a mobile 6 x 3 cm mass in the left atrium attached to the interatrial septum extending into the mitral valve. Cardiothoracic Surgery and Urology were consulted and confirmed a diagnosis of left atrial myxoma and clear cell renal cell carcinoma. The patient returned a week later due to worsening nausea and vomiting and underwent emergent nephrectomy, lymph node dissection, and colostomy due to a necrotic colon. Her condition declined over the next four months due to lung and brain metastases, infections, and other complications until she passed away.

Keywords: bedside ultrasound, echocardiography, emergency medicine, left atrial myxoma

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Authors: Sachil Kumar, Anoop Kumar Verma, Wahid Ali, Uma Shankar Singh

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Globally approximately 55.3 million people die each year. In the India there were 95 lakh annual deaths in 2013. The number of deaths resulted from homicides, suicides and unintentional injuries in the same period was about 5.7 lakh. The ever-increasing crime rate necessitated the development of methods for determining time since death. An erroneous time of death window can lead investigators down the wrong path or possibly focus a case on an innocent suspect. In this regard a research was carried out by analyzing the temperature dependent degradation of a Cardiac Troponin-T protein (cTnT) in the myocardium postmortem as a marker for time since death. Cardiac tissue samples were collected from (n=6) medico-legal autopsies, (in the Department of Forensic Medicine and Toxicology, King George’s Medical University, Lucknow India) after informed consent from the relatives and studied post-mortem degradation by incubation of the cardiac tissue at room temperature (20±2 OC), 12 0C, 25 0C and 37 0C for different time periods ((~5, 26, 50, 84, 132, 157, 180, 205, and 230 hours). The cases included were the subjects of road traffic accidents (RTA) without any prior history of disease who died in the hospital and their exact time of death was known. The analysis involved extraction of the protein, separation by denaturing gel electrophoresis (SDS-PAGE) and visualization by Western blot using cTnT specific monoclonal antibodies. The area of the bands within a lane was quantified by scanning and digitizing the image using Gel Doc. The data shows a distinct temporal profile corresponding to the degradation of cTnT by proteases found in cardiac muscle. The disappearance of intact cTnT and the appearance of lower molecular weight bands are easily observed. Western blot data clearly showed the intact protein at 42 kDa, two major (27 kDa, 10kDa) fragments, two additional minor fragments (32 kDa) and formation of low molecular weight fragments as time increases. At 12 0C the intensity of band (intact cTnT) decreased steadily as compared to RT, 25 0C and 37 0C. Overall, both PMI and temperature had a statistically significant effect where the greatest amount of protein breakdown was observed within the first 38 h and at the highest temperature, 37 0C. The combination of high temperature (37 0C) and long Postmortem interval (105.15 hrs) had the most drastic effect on the breakdown of cTnT. If the percent intact cTnT is calculated from the total area integrated within a Western blot lane, then the percent intact cTnT shows a pseudo-first order relationship when plotted against the log of the time postmortem. These plots show a good coefficient of correlation of r = 0.95 (p=0.003) for the regression of the human heart at different temperature conditions. The data presented demonstrates that this technique can provide an extended time range during which Postmortem interval can be more accurately estimated.

Keywords: degradation, postmortem interval, proteolysis, temperature, troponin

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Authors: Archana Sharma, Vijayashree Nayak, Ashok Kumar

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Three-dimensional matrices were fabricated from blend of natural-natural polymers like carrageenan-gelatin and synthetic -natural polymers such as PEG- gelatin (PEG of different molecular weights (2,000 and 6,000) using two different crosslinkers; glutaraldehyde and EDC-NHS by cryogelation technique. Blends represented a feasible approach to design 3-D scaffolds with controllable mechanical, physical and biochemical properties without compromising biocompatibility and biodegradability. These matrices possessed interconnected porous structure, good mechanical strength, biodegradable nature, constant swelling kinetics, ability to withstand high temperature and visco-elastic behavior. Hemocompatibility of cryogel matrices was determined by coagulation assays and hemolytic activity assay which demonstrated that these cryogels have negligible effects on coagulation time and have excellent blood compatibility. In vitro biocompatibility (cell-matrix interaction) inferred good cell adhesion, proliferation, and secretion of ECM on matrices. These matrices provide a microenvironment for the growth, proliferation, differentiation and secretion of ECM of different cell types such as IMR-32, C2C12, Cos-7, rat bone marrow derived MSCs and human bone marrow MSCs. Hoechst 33342 and PI staining also confirmed that the cells were uniformly distributed, adhered and proliferated properly on the cryogel matrix. An ideal scaffold used for tissue engineering application should allow the cells to adhere, proliferate and maintain their functionality. Neurotransmitter analysis has been done which indicated that IMR-32 cells adhered, proliferated and secreted neurotransmitters when they interacted with these matrices which showed restoration of their functionality. The cell-matrix interaction up to molecular level was also evaluated so to check genotoxicity and protein expression profile which indicated that these cryogel matrices are non-genotoxic and maintained biofunctionality of cells growing on these matrices. All these cryogels, when implanted subcutaneously in balb/c mice, showed no adverse systemic or local toxicity effects at implantation site. There was no significant increase in inflammatory cell count has otherwise been observed after scaffold implantation. These cryogels are supermacroporous and this porous structure allows cell infiltration and proliferation of host cells. This showed the integration and presence of infiltrated cells into the cryogel implants. Histological analysis confirmed that the implanted cryogels do not have any adverse effect in spite of host immune system recognition at the site of implantation, on its surrounding tissues and other vital host organs. In vivo biocompatibility study after in vitro biocompatibility analysis has also concluded that these synthesized cryogels act as important biological substitutes, more adaptable and appropriate for transplantation. Thus, these cryogels showed their potential for soft tissue engineering applications.

Keywords: cryogelation, hemocompatibility, in vitro biocompatibility, in vivo biocompatibility, soft tissue engineering applications

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Authors: Ishan Naidu, Jessica Ryvlin, Devin Videlefsky

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Introduction: Back pain is a leading cause of years lived with disability and economic burden, exceeding over $20 billion in healthcare costs not including indirect costs such as absence from work and caregiving. The multifactorial nature of back pain leads to treatment modalities administered by a variety of specialists, which are often disjointed. Multiple studies have found that patients receiving delayed physical therapy for lower back pain had higher medical-related costs from increased health service utilization as well as a reduced improvement in pain severity compared to early management. Uncoordinated health care delivery can exacerbate the physical and economic toll of the chronic condition, thus improvements in interdisciplinary, shared decision-making may improve outcomes. Objective: To assess whether a multidisciplinary spine clinic (MSC), consisting of orthopedic surgery, neurosurgery, pain medicine, and physiatry, alters interventional and non-interventional planning and treatment compared to a traditional unidisciplinary spine clinic (USC) including only orthopedic surgery. Methods: We conducted a retrospective cohort study with patients initially presenting for spine care to orthopedic surgeons between July 1, 2018 to June 30, 2019. Time to treatment recommendation, time to treatment and rates of treatment recommendations were assessed, including physical therapy, injections and surgery. Treatment rates were compared between MSC and USC using Pearson’s chi-square test logistic regression. Time to treatment recommendation and time to treatment were compared using log-rank test and Cox proportional hazard regression. All analyses were repeated for the propensity score (PS) matched subsample. Results: This study included 1,764 patients, with 692 at MSC and 1,072 at USC. Patients in MSC were more likely to be recommended injection when compared to USC (8.5% vs. 5.4%, p=0.01). When adjusted for confounders, the likelihood of injection recommendation remained greater in MSC than USC (Odds ratio [OR]=2.22, 95% CI: (1.39, 3.53), p=0.001). MSC was also associated with a shorter time to receiving injection recommendation versus USC (median: 21 vs. 32 days, log-rank: p<0.001; hazard ratio [HR]=1.90, 95% CI: (1.25, 2.90), p=0.003). MSC was associated with a higher likelihood of injection treatment (OR=2.27, 95% CI: (1.39, 3.73), p=0.001) and shorter lead time (HR=1.98, 95% CI: (1.27, 3.09), p=0.003). PS-matched analyses yielded similar conclusions. Conclusions: Care delivered at a multidisciplinary spine clinic was associated with a higher likelihood of recommending injection and a shorter lead time to injection administration when compared to a traditional unidisciplinary spine surgery clinic. Multidisciplinary clinics may facilitate coordinated care amongst different specialties resulting in increased utilization of less invasive treatment modalities while also improving care efficiency. The multidisciplinary clinic model is an important advancement in care delivery and communication, which can be used as a powerful method of improving patient outcomes as treatment guidelines evolve.

Keywords: coordinated care, epidural steroid injection, multi-disciplinary, non-invasive

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Authors: Stephane Maingard, Babu Paturi, Maura Daly, Finnola Armstrong

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Background: Perinatal optimization involves the implementation of twelve intervention bundles of care at Our Lady of Lourdes Hospital, reliably delivering evidence-based interventions in the antenatal, intrapartum, and neonatal period to improve preterm outcomes. These key interventions (e.g. Antenatal steroids, Antenatal counselling, Optimal cord management, Respiratory management etc.) are based on WHO (World Health Organization, BAPM (British Association of Perinatal Medicine), and the latest 2022 European Consensus guidelines recommendations. Methodology: In February 2023, a quality improvement project team (pediatricians, neonatologists, obstetricians, clinical skills managers) was established, and a project implementation plan was developed. The Program Study Act implemented the following: 1. Antenatal consultation pathway, 2. Creation and implementation of a perinatal checklist for preterm births less than 34 weeks of gestation, 3. Process changes to ensure the checklist is completed, 4. Completion of parent and staff surveys, 5. Ongoing training. We collected and compared a range of data before and after implementation. Results: Preliminary analysis so far at 1 month demonstrates improvement in the following areas: 50% increase in antenatal counselling. Right place of birth increased from 85% to 100%. Magnesium sulphate increased from 56% to 100%. No change was observed in buccal colostrum administration (28%), delayed cord clamping (75%), caffeine administration (100%), blood glucose level at one hour of life > 2,6mmol (85%). There was also no change noted in respiratory support at resuscitation, CPAP only (47%), IPPV with CPAP (45%), IPPV with intubation (20%), and surfactant administration (28%). A slight decrease in figures was noted in the following: steroid administration from 80% to 75% and thermal care obtaining optimal temperature on admission (65% to 50%). Discussion: Even though the findings are preliminary, the directional improvement shows promise. Improved communication has been achieved between all stakeholders, including our patients, who are key team members. Adherence to the bundles of care will help to improve survival and neurodevelopmental outcomes as well as reduce the length of stay, thereby overall reducing the financial cost, considering the lifetime cost of cerebral palsy is estimated at €800,000 and reducing the length of stay can result in savings of up to €206,000. Conclusion: Preliminary results demonstrate improvements across a range of patient, process, staff, and financial outcomes. Our future goal is a seamless pathway of patient centered care for babies and their families. This project is an interdisciplinary collaboration to implement best practices for a vulnerable patient cohort. Our two main challenges are changing our organization’s culture as well as ensuring the sustainability of the project.

Keywords: perinatal, optimization, antenatal, counselling, IPPV

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Authors: Oleg Reva, Ilya Korotetskiy, Marina Lankina, Murat Kulmanov, Aleksandr Ilin

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Molecular docking approaches are widely used for design of new antibiotics and modeling of antibacterial activities of numerous ligands which bind specifically to active centers of indispensable enzymes and/or key signaling proteins of pathogens. Widespread drug resistance among pathogenic microorganisms calls for development of new antibiotics specifically targeting important metabolic and information pathways. A generally recognized problem is that almost all molecular targets have been identified already and it is getting more and more difficult to design innovative antibacterial compounds to combat the drug resistance. A promising way to overcome the drug resistance problem is an induction of reversion of drug resistance by supplementary medicines to improve the efficacy of the conventional antibiotics. In contrast to well established computer-based drug design, modeling of drug resistance reversion still is in its infancy. In this work, we proposed an approach to identification of compensatory genetic variants reducing the fitness cost associated with the acquisition of drug resistance by pathogenic bacteria. The approach was based on an analysis of the population genetic of Mycobacterium tuberculosis and on results of experimental modeling of the drug resistance reversion induced by a new anti-tuberculosis drug FS-1. The latter drug is an iodine-containing nanomolecular complex that passed clinical trials and was admitted as a new medicine against MDR-TB in Kazakhstan. Isolates of M. tuberculosis obtained on different stages of the clinical trials and also from laboratory animals infected with MDR-TB strain were characterized by antibiotic resistance, and their genomes were sequenced by the paired-end Illumina HiSeq 2000 technology. A steady increase in sensitivity to conventional anti-tuberculosis antibiotics in series of isolated treated with FS-1 was registered despite the fact that the canonical drug resistance mutations identified in the genomes of these isolates remained intact. It was hypothesized that the drug resistance phenotype in M. tuberculosis requires an adjustment of activities of many genes to compensate the fitness cost of the drug resistance mutations. FS-1 cased an aggravation of the fitness cost and removal of the drug-resistant variants of M. tuberculosis from the population. This process caused a significant increase in genetic heterogeneity of the Mtb population that was not observed in the positive and negative controls (infected laboratory animals left untreated and treated solely with the antibiotics). A large-scale search for linkage disequilibrium associations between the drug resistance mutations and genetic variants in other genomic loci allowed identification of target proteins, which could be influenced by supplementary drugs to increase the fitness cost of the drug resistance and deprive the drug-resistant bacterial variants of their competitiveness in the population. The approach will be used to improve the efficacy of FS-1 and also for computer-based design of new drugs to combat drug-resistant infections.

Keywords: complete genome sequencing, computational modeling, drug resistance reversion, Mycobacterium tuberculosis

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Authors: Rabab Makki

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Bone mineral density and bone metabolism are affected by various factors such as genetic, endocrine, mechanical and nutritional. Our understanding of nutritional influences on bone health is limited because most studies have focused on calcium. This study investigated the dietary factors which are likely t contribute to Osteoporosis in Saudi post-menopausal women, and correlated it with BMD. This is a case controlled study involved 36 postmenopausal Saudi females selected from the Orthopedics and osteoporosis outpatient clinics, and 25 postmenopausal Saudi females as controls from the primary clinic of Military Hospital in Riyadh. The women were diagnosed as osteoporotic based on the BMD measurement at any site (left femur neck, right femur neck, left total hip or right total hip or spine). Both the controls and the Osteoporotics were over 50 years of age and BMI between 31-34 kg/m2 had 2nd degree obesity, and were not free from other problems such as diabetes, hypertension, etc. Subjects (osteoporotics and controls) were interviewed to called data on demographic characterstics, medical history, dietary intake anthropometry (height and weight) bone mineral density. Blood samples were collected from subjects (Osteoporotics and controls). Analysis of serum calcium, vitamin D, phosphate were done at the main laboratory at Military Hospital Riyadh, by the laboratory technician while BMD was determined at the department of Nuclear Medicine by an expert technician and results were interpreted by radiologist.Data on frequency of consumption of animal food (meat, eggs, poultry and fish) and diary foods (milk, yogurt, cheese) of osteoporotic was less than control. In spite of the low intake there was no association with BMD.In general, the vegetables and fruits were consumed less by the osteoporotics than control. The only fruit which had shown a significant positive correlation is banana with right and left hip BMD total probably due to high potassium and minerals content which likely to prevent bone resorption. Mataziz vegetables combination of wheat showed a significant positive correlation with the same site (total right and left hip). Both osteoporotics abd controls were consuming table sugar. (But the sweet intake showed a significant negative correlation with left neck femur BMD, suggesting sucrose increase urinary calcium loss. Both osteoporotic and controls were consuming Arabic coffee. A negative significant correlation between intake of Arabic coffee and BMD of right neck femur of osteoporosis patient was observed. It could be suggested that increased intake of fruits and vegetables, might promote bone density while high intake of coffee and sugars might affect bone density, no significant correlation was observed between BMD at any site and diary product. We can say the major risk factors are inadequate nutrition. Further studies are needed among Saudi population to confirm these results.

Keywords: osteoporosi, Saudia Arabia, Riyadh Armed Forces, postmenopausal women

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Authors: Richele P. Severino, Maria M. F. Alchaar, Lorena R. F. De Sousa, Patrik S. Vital, Ana G. Silva, Rosy I. M. A. Ribeiro

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Recognized as a global biodiversity hotspot, the Cerrado (Brazil) presents an extreme abundance of endemic species and it is considered to be one of the biologically richest tropical savanna regions in the world. Erythroxylum genus is found in Cerrado and chemically is characterized by the presence of tropane alkaloids, among them cocaine, a natural alkaloid produced by Erythroxylum coca Lam., which was used as a local anesthetic in small surgeries. However, cocaine gained notoriety due to its psychoactive activity in the Central Nervous System (CNS), becoming one of the major problems of public health today. Some species of Erythroxylum are referred to in the literature as having pharmacological potential, which provide alkaloids, terpenoids, and flavonoids. E. vacciniifolium Mart., commonly known as 'catuaba', is used as a central nervous system stimulant and has aphrodisiac properties and E. pelleterianum A. St.-Hil. in the treatment of stomach pains. Already E. myrsinites Mart. and E. suberosum A. St.-Hil. are used in the tannery industry. Species of Erythroxylum are also used in folk medicine for various diseases, against diabetes, antiviral, fungicidal, cytotoxicity, among others. The Cerrado is recognized as the richer savannah in the world in biodiversity but little explored from the chemical view. In our on-going study of the chemistry of Erythroxylum genus, we have investigated four specimens collected in central Cerrado of Brazil: E. campestre (EC), E. deciduum (ED), E. suberosum (ES) and E. tortuosum (ET). The cytotoxic activity of extracts was evaluated using HeLa cells, in vitro assays. The chemical investigation was performed preparing the extracts using n-hexane (H), dichloromethane (D), ethyl acetate (E) and methanol (M). The cells were treated with increasing concentrations of extracts (50, 75 and 100 μg/mL) diluted in DMSO (1%) and DMEM (0.5% FBS and 1% P/S). The IC₅₀ values were determined measured spectrophotometrically at 570 nm, after incubation of HeLa cell line for 48 hours using the MTT (SIGMA M5655), and calculated by nonlinear regression analysis using GraphPad Prism software. All the assays were done in triplicate and repeated at least two times. The cytotoxic assays showed some promising results with IC₅₀ values less than 100 μg/mL (ETD = 38.5 μg/mL; ETM = 92.3 μg/mL; ESM = 67.8 μg/mL; ECD = 24.0 μg/mL; ECM = 32.9; EDA = 44.2 μg/mL). The chemical profile study of ethyl acetate (E) and methanolic (M) extracts of E. tortuosum leaves was performed by LC-MS, and the structures of the compounds were determined by analysis of ¹H, HSQC and HMBC spectra, and confirmed by comparison with the literature data. The investigation led to six substances: α-amyrin, β-amyrin, campesterol, stigmastan-3,5-diene, β-sitosterol and 7,4’-di-O-methylquercetin-3-O-β-rutinoside, with flavonoid the major compound of extracts. By alkaline extraction of the methanolic extract, it was possible to identify three alkaloids: tropacocaine, cocaine and 6-methoxy-8-methyl-8-azabicyclo[3.2.1]octan-3-ol. The results obtained are important for the chemical knowledge of the Cerrado biodiversity and brought a contribution to the chemistry of Erythroxylum genus.

Keywords: cytotoxicity, Erythroxylum, chemical profile, secondary metabolites

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Authors: Kamelia Hamza

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Background: Proton pump inhibitors (PPIs) are the most prescribed drug classes for pediatric gastroesophageal reflux disease (GERD).Many patients are treated with these drugs for atypical manifestations attributed to gastroesophageal reflux (GER), even in the absence of proved causal relationship. There is an impression of increase use of PPI's treatment for reflux in "clalit health services," the largest health organization in Israel. In the recent years, the medicine is given without restriction, it's not limited to pediatric gastroenterologists only, but pediatricians and family doctors. The objective of this study is to evaluate the hypothesis that exposure to PPIs during the first year of life is associated with an increased risk of developing late adverse diseases: pneumonia, asthma, AGE, IBD, celiac disease, allergic disorders, obesity, attention deficit hyperactivity disorders (ADHD), autism spectrum disorders (ASD). Methods: The study is a retrospective case-control cohort study based on a computerized database of Clalit Health Services (CHS). It includes 9844 children born between 2002-2018 and reported to complain of at least one of the symptoms (reflux/ spitting up, irritability, feeding difficulties, colics). The study population included the study group (n=4922) of children exposed to PPIs at any time prior to the first year of life and a control group (n=4922) child not exposed to PPIs who were matched to each case of the study group on age, race, socioeconomic status, and year of birth. The prevalence of late complications/diseases in the study group was compared with the prevalence of late complications/diseases diagnosis between 2002-2020 in the control group. Odds ratios and 95% confidence intervals were calculated by using logistic regression models. Results: We found that compared to the control group, children exposed to PPIs in the first year of life had an increased risk of developing several late complications/ disorders: pneumonia, asthma, various allergies (urticaria, allergic rhinitis, or allergic conjunctivitis) OR, inhalant allergies, and food allergies. In addition, they showed an increased risk of being diagnosed with ADHD or ASD, but children exposed to PPIs in the first year of life had decrease the risk of obesity by 17% (OR 0.825, 95%CI 0.697-0.976). Conclusions: We found significant associations between the use of PPIs during the first year of life and subsequent development of late complications/diseases such as respiratory diseases, allergy diseases, ADHD, and ASD. More studies are needed to prove causality and determine the mechanism behind the effect of PPIs and the development of late complications.

Keywords: acid suppressing medications, proton pump inhibitors, histamine 2 blocker, late complications, gastroesophageal reflux, gastroesophageal reflux disease, acute gastroenteritis, community acquired pneumonia, asthma, allergic diseases, obesity, inflammatory bowel diseases, ulcerative colitis, crohn disease, attention deficit hyperactivity disorders, autism spectrum disorders

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Authors: Sidra Jawed

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The accessibility constructs and the body privilege discourse has been a major problem while dealing with health inequities and inaccessibility. The inherent problem in this arbitrary view of disability is that disability would never be the productive way of living. For past thirty years, disability activists have been working to differentiate ‘impairment’ from ‘disability’ and probing for more understanding of limitation imposed by society, this notion is ultimately known as the Social Model of Disability. The vulnerable population as disability community remains marginalized and seen relentlessly fighting to highlight the importance of social factors. It does not only constitute physical architectural barriers and famous blue symbol of access to the healthcare but also invisible, intangible barriers as attitudes and behaviours. Conventionally the idea of ‘disability’ has been laden with prejudiced perception amalgamating with biased attitude. Equity in contemporary setup necessitates the restructuring of organizational structure. Apparently simple, the complex interplay of disability and contemporary healthcare set up often ends up at negotiating vital components of basic healthcare needs. The role of society is indispensable when it comes to people with disability (PWD), everything from the access to healthcare to timely interventions are strongly related to the set up in place and the attitude of healthcare providers. It is vital to understand the association between assumptions and the quality of healthcare PWD receives in our global healthcare setup. Most of time the crucial physician-patient relationship with PWD is governed by the negative assumptions of the physicians. The multifaceted, troubled patient-physicians’ relationship has been neglected in past. To compound it, insufficient work has been done to explore physicians’ perspective about the disability and access to healthcare PWD have currently. This research project is directed towards physicians’ perspective on the intersection of health and access of healthcare for PWD. The principal aim of the study is to explore the perception of disability in family medicine physicians, highlighting the underpinning of medical perspective in healthcare institution. In the quest of removing barriers, the first step must be to identify the barriers and formulate a plan for future policies, involving all the stakeholders. There would be semi-structured interviews to explore themes as accessibility, medical training, construct of social model and medical model of disability, time limitations, financial constraints. The main research interest is to identify the obstacles to inclusion and marginalization continuing from the basic living necessities to wide health inequity in present society. Physicians point of view is largely missing from the research landscape and the current forum of knowledge with regards to physicians’ standpoint. This research will provide policy makers with a starting point and comprehensive background knowledge that can be a stepping stone for future researches and furthering the knowledge translation process to strengthen healthcare. Additionally, it would facilitate the process of knowledge translation between the much needed medical and disability community.

Keywords: disability, physicians, social model, accessibility

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Authors: K. J. Sannapapamma, H. Malligawad Lokanath, Sakeena Naikwadi

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Eco-friendly textiles are gaining importance among the consumers and textile manufacturers in the healthcare sector due to increased environmental pollution which leads to several health and environmental hazards. Hence, the research was designed to cultivate and develop the organic cotton knit, to prepare and characterize the Vetiver oil microcapsules for textile finishing and to access the wash durability of finished knits. The cotton SAHANA variety grown under organic production systems was processed and spun into 30 single yarn dyed with four natural colorants (Arecanut slurry, Eucalyptus leaves, Pomegranate rind and Indigo) and eco dyed yarn was further used for development of single jersy knitted fabric. Vetiveria zizanioides is an aromatic grass which is being traditionally used in medicine and perfumery. Vetiver essential oil was used for preparation of microcapsules by interfacial polymerization technique subjected to Gas Chromatography Mass Spectrometry (GCMS), Fourier Transform Infrared Spectroscopy (FTIR), Thermo Gravimetric Analyzer (TGA) and Scanning Electron Microscope (SEM) for characterization of microcapsules. The knitted fabric was finished with vetiver oil microcapsules by exhaust and pad dry cure methods. The finished organic knit was assessed for laundering on antimicrobial efficiency and aroma intensity. GCMS spectral analysis showed that, diethyl phthalate (28%) was the major compound found in vetiver oil followed by isoaromadendrene epoxide (7.72%), beta-vetivenene (6.92%), solavetivone (5.58%), aromadenderene, azulene and khusimol. Bioassay explained that, the vetiver oil and diluted vetiver oil possessed greater zone of inhibition against S. aureus and E. coli than the coconut oil. FTRI spectra of vetiver oil and microcapsules possessed similar peaks viz., C-H, C=C & C꞊O stretching and additionally oil microcapsules possessed the peak of 3331.24 cm^-1 at 91.14 transmittance was attributed to N-H stretches. TGA of oil microcapsules revealed that, there was a minimum weight loss (5.835%) recorded at 467.09°C compared to vetiver oil i.e., -3.026% at the temperature of 396.24°C. The shape of the microcapsules was regular and round, some were spherical in shape and few were rounded by small aggregates. Irrespective of methods of application, organic cotton knits finished with microcapsules by pad dry cure method showed maximum zone of inhibition compared to knits finished by exhaust method against S. aureus and E. coli. The antimicrobial activity of the finished samples was subjected to multiple washing which indicated that knits finished with pad dry cure method showed a zone of inhibition even after 20^th wash and better aroma retention compared to knits finished with the exhaust method of application. Further, the group of respondents rated that the 5^th washed samples had the greater aroma intensity in both the methods than the other samples. Thus, the vetiver microencapsulated organic cotton knits are free from hazardous chemicals and have multi-functional properties that can be suitable for medical and healthcare textiles.

Keywords: exhaust and pad dry cure finishing, interfacial polymerization, organic cotton knits, vetiver oil microcapsules

Procedia PDF Downloads 281

Authors: Abebe Yimer, Sirawdink Fikereyesus Forsido, Getachew Addis, Abebe Ayelign

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Background: Oxidative stress has been an important health problem as itinduceschronic diseases such as cancer, cardiovascular, diabetics, and neurodegenerative disease. Plant source natural antioxidant has gained attention as synthetic antioxidant negatively impact human health. Wild edible plants arecheap source of dietary-medicine in mainly rural communityin south-west Ethiopia and elsewhere the country. Thus, the study aimed to determine total pheneol,flavoinoids, antioxidant, vitamin C, and beta-carotene content from wild edible plants Solanum nigrum L., Vigna membranacea A. Rich, Dioscorea praehensilis Benth., Trilepisium madagascariense D.C.andCleome gynandra L. Methods: Methanol was used to extract samples of oven-dried edible plants. Total phenolic compound (TPC) was determined using a Folin Ciocalteu method, whereas total flavonoid content (TFC) was determined using the Aluminium chloride colorimetric method. By using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) tests, antioxidant activities were evaluated in vitro. Additionally, beta-carotene was assessed using a spectrophotometric technique, whilst vitamin C was determined using a titration approach. Results: Total flavonoid contentranged from 0.85±0.03 to 11.25±0.01 mg CE/g in D. praehensilis Benth. tuber and C. gynandra L, respectively. Total phenolic compounds varied from 0.25±0.06 GAE/g in D. praehensilis Benth tuber to 35.73±2.52 GAE/g in S.nigrum L. leaves. In the DPPH test, the highest antioxidant value (87.65%) was obtained in the S.nigrum L. leaves, whereas the smallest amount of antioxidant (50.12%)was contained in D. praehensilis Benth tuber. Similarly in FRAP assay,D. praehensilis Benth tuber showed the least reducing potential(49.16± 2.13mM Fe2+/100 g)whilst the highest reducing potential was presented in the S.nigrum L. leaves(188.12±1.13 mM Fe2+/100 g). The beta-carotene content was found between 11.81±0.00 mg/100g in D. praehensilis Benth tubers to 34.49±0.95 mg/100g in V. membranacea A. Rich leaves. The concentration of vitamin C ranged from 10.00±0.61 in D. praehensilis Benth tubers to 45±1.80 mg/100g in V. membranacea A. Rich leaves. The results showed that high positive linear correlations between TPC and TFC of WEPs (r=0.828), as well as between FRAP and total phenolic contents (r = 0.943) and FRAP and vitamin C (r= 0.928). Conclusion: These findings showed the total phenolic and flavonoid contents of Solanum nigrum L. and Cleome gynandra L, respectively, are abundant. The outcome may be used as a natural supply of dietary antioxidants, which may be useful in preventing oxidative stress. The study's findings also showed that Vigna membranacea A. Rich leaves were cheap source of vitamin C and beta-carotene for people who consumed these wild green. Additional research on the in vivo antioxidant activity, toxicological analysis, and promotion of these wild food plants for agricultural production should be taken into consideration.

Keywords: antioxidant activity, beta-carotene, flavonoids, phenolic content, and vitamin c

Procedia PDF Downloads 102

Authors: Bozena Tyliszczak, Anna Drabczyk, Sonia Kudlacik-Kramarczyk, Agnieszka Sobczak-Kupiec

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Introduction: Nanomaterials become one of the leading materials in the synthesis of various compounds. This is a reason for the fact that nano-size materials exhibit other properties compared to their macroscopic equivalents. Such a change in size is reflected in a change in optical, electric or mechanical properties. Among nanomaterials, particular attention is currently directed into gold nanoparticles. They find application in a wide range of areas including cosmetology or pharmacy. Additionally, nanogold may be a component of modern wound dressings, which antibacterial activity is beneficial in the viewpoint of the wound healing process. Specific properties of this type of nanomaterials result in the fact that they may also be applied in cancer treatment. Studies on the development of new techniques of the delivery of drugs are currently an important research subject of many scientists. This is due to the fact that along with the development of such fields of science as medicine or pharmacy, the need for better and more effective methods of administering drugs is constantly growing. The solution may be the use of drug carriers. These are materials that combine with the active substance and lead it directly to the desired place. A role of such a carrier may be played by gold nanoparticles that are able to covalently bond with many organic substances. This allows the combination of nanoparticles with active substances. Therefore gold nanoparticles are widely used in the preparation of nanocomposites that may be used for medical purposes with special emphasis on drug delivery. Methodology: As part of the presented research, synthesis of composites was carried out. The mentioned composites consisted of the polymer matrix and gold nanoparticles that were introduced into the polymer network. The synthesis was conducted with the use of a crosslinking agent, and photoinitiator and the materials were obtained by means of the photopolymerization process. Next, incubation studies were conducted using selected liquids that simulated fluids are occurring in the human body. The study allows determining the biocompatibility of the tested composites in relation to selected environments. Next, the chemical structure of the composites was characterized as well as their sorption properties. Conclusions: Conducted research allowed for the preliminary characterization of prepared polymer composites containing gold nanoparticles in the viewpoint of their application for biomedical use. Tested materials were characterized by biocompatibility in tested environments. What is more, synthesized composites exhibited relatively high swelling capacity that is essential in the viewpoint of their potential application as drug carriers. During such an application, composite swells and at the same time releases from its interior introduced active substance; therefore, it is important to check the swelling ability of such material. Acknowledgements: The authors would like to thank The National Science Centre (Grant no: UMO - 2016/21/D/ST8/01697) for providing financial support to this project. This paper is based upon work from COST Action (CA18113), supported by COST (European Cooperation in Science and Technology).

Keywords: nanocomposites, gold nanoparticles, drug carriers, swelling properties

Procedia PDF Downloads 116

Authors: Jason M. Hegenauer, Nicholas Fucci

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In the late 1990s, a major deinstitutionalization movement of elderly patients took place, since which, the design of long-term care facilities has not been adequately analyzed in the United States. Over the course of the last 25 years, major innovations in construction methods, technology, and medicine have been developed, drastically changing the landscape of healthcare architecture. In light of recent events, and the expected increase in elderly populations with the aging of the baby-boomer generation, it is evident that reconsideration of these facilities is essential for the proper care of aging populations. The global response has been effective in stifling this pandemic; however, widespread disease still poses an imminent threat to the human race. Having witnessed the devastation Covid-19 has reaped throughout nursing homes and long-term care facilities, it is evident that the current strategies for protecting our most vulnerable populations are not enough. Light renovation of existing facilities and previously overlooked considerations for new construction projects can drastically lower the risk at nursing homes and long-term care facilities. A reconfigured entry sequence supplements several of the features which have been long-standing essentials of the design of these facilities. This research focuses on several aspects identified as needing improvement, including indoor environment quality, security measures incorporated into healthcare architecture and design, and architectural mitigation strategies for sick building syndrome. The results of this study have been compiled as 'best practices' for the design of future healthcare construction projects focused on the health, safety, and quality of life of the residents of these facilities. These design strategies, which can easily be implemented through renovation of existing facilities and new construction projects, minimize risk of infection and spread of disease while allowing routine functions to continue with minimal impact, should the need for future lockdowns arise. Through the current lockdown procedures, which were implemented during the Covid-19 pandemic, isolation of residents has caused great unrest and worry for family members and friends as they are cut off from their loved ones. At this time, data is still being reported, leaving infection and death rates inconclusive; however, recent projections in some states list long-term care facility deaths as high as 60% of all deaths in the state. The population of these facilities consists of residents who are elderly, immunocompromised, and have underlying chronic medical conditions. According to the Centers for Disease Control, these populations are particularly susceptible to infection and serious illness. The obligation to protect our most vulnerable population cannot be overlooked, and the harsh measures recently taken as a response to the Covid-19 pandemic prove that the design strategies currently utilized for doing so are inadequate.

Keywords: building security, healthcare architecture and design, indoor environment quality, new construction, sick building syndrome, renovation

Procedia PDF Downloads 98

Authors: Maureen Kamau, Gulnaz Mohamoud, Adelaide Lusambili, Njeri Nyanja

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Life expectancy has increased over the last century amongst older individuals, and in particular, those 60 years and over. The World Health Organization estimates that the world's population of persons over 60 years will rise to 22 per cent by the year 2050. Ageing is associated with increasing disability, multiple chronic conditions, and an increase in the use of health services. These multiple chronic conditions are managed with polypharmacy. Polypharmacy has numerous adverse effects including non-adherence, poor compliance to the various medications, reduced appetite, and risk of fall. Studies on polypharmacy and ageing are few and poorly understood especially in low and middle - income countries. The aim of this study was to explore the knowledge, attitudes and beliefs of older people towards polypharmacy. A qualitative study of 15 patients aged 60 years and above, taking more than five medications per day were conducted at the Aga Khan University using Semi-structured in-depth interviews. Three interviews were pilot interviews, and data analysis was performed on 12 interviews. Data were analyzed using NVIVO 12 software. A thematic qualitative analysis was carried out guided by Braun and Clarke (2006) framework. Themes identified; - knowledge of their co-morbidities and of the medication that older persons take, sources of information about medicines, and storage of the medication, experiences and attitudes of older patients towards polypharmacy both positive and negative, older peoples beliefs and their coping mechanisms with polypharmacy. The study participants had good knowledge on their multiple co-morbidities, and on the medication they took. The patients had positive attitudes towards medication as it enhanced their health and well-being, and enabled them to perform their activities of daily living. There was a strong belief among older patients that the medications were necessary for their health. All these factors enhanced compliance to the multiple medication. However, some older patients had negative attitudes due to the pill burden, side effects of the medication, and stigma associated with being ill. Cost of healthcare was a concern, with most of the patients interviewed relying on insurance to cover the cost of their medication. Older patients had accepted that the medication they were prescribed were necessary for their health, as it enabled them to complete their activities of daily living. Some concerns about the side effects of the medication arose, and brought about the need for patient education that would ensure that the patients are aware of the medications they take, and potential side effects. The effect that the COVID 19 pandemic had in the healthcare of the older patients was evident by the number of the older patients avoided coming to the hospital during the period of the pandemic. The relationship with the primary care physician and the older patients is an important one, especially in LMICs such as Kenya, as many of the older patients trusted the doctors wholeheartedly to make the best decision about their health and about their medication. Prescription review is important to avoid the use of potentially inappropriate medication.

Keywords: polypharmacy, older patients, multiple chronic conditions, Kenya, Africa, qualitative study, indepth interviews, primary care

Procedia PDF Downloads 100

Authors: Anuj Tyagi, Balwinder Singh, Naveen Kumar B. T., Niraj K. Singh

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Characterization of diverse microbial communities in specific environment plays a crucial role in the better understanding of their functional relationship with the ecosystem. It is now well established that gut microbiome of fish is not the simple replication of microbiota of surrounding local habitat, and extensive species, dietary, physiological and metabolic variations in fishes may have a significant impact on its composition. Moreover, overuse of antibiotics in human, veterinary and aquaculture medicine has led to rapid emergence and propagation of antibiotic resistance genes (ARGs) in the aquatic environment. Microbial communities harboring specific ARGs not only get a preferential edge during selective antibiotic exposure but also possess the significant risk of ARGs transfer to other non-resistance bacteria within the confined environments. This phenomenon may lead to the emergence of habitat-specific microbial resistomes and subsequent emergence of virulent antibiotic-resistant pathogens with severe fish and consumer health consequences. In this study, gut microbiota of freshwater carp (Labeo rohita) was investigated by shotgun metagenomics to understand its taxonomic composition and functional capabilities. Metagenomic DNA, extracted from the fish gut, was subjected to sequencing on Illumina NextSeq to generate paired-end (PE) 2 x 150 bp sequencing reads. After the QC of raw sequencing data by Trimmomatic, taxonomic analysis by Kraken2 taxonomic sequence classification system revealed the presence of 36 phyla, 326 families and 985 genera in the fish gut microbiome. At phylum level, Proteobacteria accounted for more than three-fourths of total bacterial populations followed by Actinobacteria (14%) and Cyanobacteria (3%). Commonly used probiotic bacteria (Bacillus, Lactobacillus, Streptococcus, and Lactococcus) were found to be very less prevalent in fish gut. After sequencing data assembly by MEGAHIT v1.1.2 assembler and PROKKA automated analysis pipeline, pathway analysis revealed the presence of 1,608 Metacyc pathways in the fish gut microbiome. Biosynthesis pathways were found to be the most dominant (51%) followed by degradation (39%), energy-metabolism (4%) and fermentation (2%). Almost one-third (33%) of biosynthesis pathways were involved in the synthesis of secondary metabolites. Metabolic pathways for the biosynthesis of 35 antibiotic types were also present, and these accounted for 5% of overall metabolic pathways in the fish gut microbiome. Fifty-one different types of antibiotic resistance genes (ARGs) belonging to 15 antimicrobial resistance (AMR) gene families and conferring resistance against 24 antibiotic types were detected in fish gut. More than 90% ARGs in fish gut microbiome were against beta-lactams (penicillins, cephalosporins, penems, and monobactams). Resistance against tetracycline, macrolides, fluoroquinolones, and phenicols ranged from 0.7% to 1.3%. Some of the ARGs for multi-drug resistance were also found to be located on sequences of plasmid origin. The presence of pathogenic bacteria and ARGs on plasmid sequences suggested the potential risk due to horizontal gene transfer in the confined gut environment.

Keywords: antibiotic resistance, fish gut, metabolic pathways, microbial diversity

Procedia PDF Downloads 144

Authors: Nadia Zahra Karimi Khiavi, Amir Ghiami Rad

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Due to the high likelihood of injuries in karate, karatekas' injuries warrant special treatment. This study explores the prevalence of karate injuries in East Azerbaijan, Iran and provides a model for karatekas to use in the prevention of such injuries. This study employs a descriptive approach. Male and female participants with a brown belt or above in either control or non-control styles in East Azerbaijan province are included in the study's statistical population. A statistical sample size of 100 people was computed using the tools employed (smartpls), and the samples were drawn at random from all clubs in the province with the assistance of the Karate Board in order to give a model for the prevention of karate injuries. Information was gathered by means of a survey that made use of the Standard Questionnaire for Australian Sports Medicine Injury Reports. The information is presented in the form of tables and samples, and descriptive statistics were used to organise and summarise the data. Control and non-control independent t-tests were conducted using SPSS version 20, and structural equation modelling (pls) was utilised for injury prevention modelling at a 0.05 level of significance. The results showed that the most common areas of injury among the control groups were the upper limbs (46.15%), lower limbs (34.61%), trunk (15.38%), and head and neck (3.84%). The most common types of injuries were broken bones (34.61%), sprain or strain (23.13%), bruising and contusions (23.13%), trauma to the face and mouth (11.53%), and damage to the nerves (69.69%). Uncontrolled committees are most likely to sustain injuries to the head and neck (33.33%), trunk (25.92%), upper limbs (22.22%), and lower limbs (18.51%). The most common injuries were to the mouth and face (33.33%), dislocations and fractures (22.22%), aspirin and strain (22.22%), bruises and contusions (18.51%), and nerves (70%), in that order. Among those who practice control kata, injuries to the upper limb account for 45.83%, the lower limb for 41.666%, the trunk for 8.33%, and the head and neck for 4.166%. The most common types of injuries are dislocations and fractures (41.66 per cent), aspirin and strain (29.16 per cent), bruising and bruises (16.66 per cent), and nerves (12.5%). Injuries to the face and mouth were not reported among those practising the control kata. By far, the most common sites of injury for those practising uncontrolled kata were the lower limb (43.74%), upper limb (39.13%), trunk (13.14%), and head and neck (4.34%). The most common types of injuries were dislocations and fractures (34.82%), aspirin and strain (26.08%), bruises and contusions (21.73%), mouth and face (13.14%), and nerves. Teaching the concepts of cooling and warming (0.591) and enhancing the degree of safety in the sports environment (0.413) were shown to play the most essential roles in reducing sports injuries among karate practitioners of controlling and uncontrolled styles, respectively. Use of common sports gear (0.390), Modification of training programme principles (0.341), Formulation of an effective diet plan for athletes (0.284), Evaluation of athletes' physical anatomy, physiology, chemistry, and physics (0.247).

Keywords: sports injuries, karate, prevention, cooling and warming

Procedia PDF Downloads 101

Authors: Manushi Srivastava

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Introduction: Doctor’s role, and relation with respect to patient care is at the core of medical ethics. The rapid pace of medical advances along with increasing consumer awareness about their rights and hike in cost of effective health care demand a robust, transparent and patient-friendly medical care system. However, doctors’ role performance is still in the frame of activity-passivity model of Doctor-Patient Relationship (DPR) where doctors act as parent and use to instruct their patients, without their consensus that is not going to help in the 21st century. Thus the current situation is a new challenge for traditional doctor-patient relationship after the introduction of Consumer Protection Act (CPA) in medical profession and the same is evidenced by increasing cases of medical litigation. To strengthen this system of medical services, the doctor plays a vital role, and the same should be reviewed in the present context. Objective: To understand the opinion of consultants regarding medical negligence and effect of Consumer Protection Act in terms of current practices of patient care. Method: This is a cross-sectional study in which both quantitative and qualitative methods are applied. Total 69 consultants were selected from multi-specialty hospitals of densely populated Varanasi city catering a population of about 1.8 million. Two-stage sampling was used for selection of respondents. At the first stage, selection of major wards (Medicine, Surgery, Ophthalmology, Gynaecology, Orthopaedics, and Paediatrics) was carried out, which are more susceptible to medical negligence. At the second stage, selection of consultants from the respective wards was carried out. In-depth Interviews were conducted with the help of semi-structured schedule. Two case studies of medical negligence were also carried out as part of the qualitative study. Analysis: Data were analyzed with the help of SPSS software (21.0 trial version). Semi-structured research tool was used to know consultant’s opinion about the pattern of medical negligence cases, litigations and claims made by patient community and inclusion of government medical services in CPA. Statistical analysis was done to describe data, and non-parametric test was used to observe the association between the variables. Analysis of Verbatim was used in case-study. Findings and Conclusion: Majority (92.8%) of consultants felt changes in the behaviour of community (patient) after implementation of CPA, as it had increased awareness about their rights. Less than half of the consultants opined that Medical Negligence is an Unintentional act of doctors and generally occurs due to communication gap and behavioural problem between doctor and patients. Experienced consultants ( > 10 years) pointed out that unethical practice by doctors and mal-intention of patient to harass doctors were additional reasons of Medical Negligence. In-depth interview revealed that now patients’ community expects more transparency and hence they demand cafeteria approach in diagnosis and management of cases. Thus as study results, we propose ‘Agreement Model’ of DPR to re-ensure ethical practice in medical profession.

Keywords: doctors, communication, consumer protection act (CPA), medical error

Procedia PDF Downloads 159

Authors: David Tennison

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Epistemic injustice, an injustice done to a person specifically in their capacity as a “knower”, is a subtle form of discrimination, yet its effects can be as dehumanizing and damaging as more overt forms of discrimination. The lens of epistemic injustice has, in recent years, been fruitfully applied to the field of healthcare, examining questions of agency, power, credibility and belief in doctor-patient interactions. Contested illness patients (e.g., those with illnesses lacking scientific consensuses such as fibromyalgia (FM), Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) and Long Covid) face higher levels of scrutiny than other patient groups and are often disbelieved or dismissed when their ailments cannot be easily imaged or tested for- often encapsulated by the expression “it’s all in your head”. Using the case study of FM, the trials of contested illness patients in healthcare can be conceptualized in terms of epistemic injustice, and what is going wrong in these doctor-patient relationships can be effectively diagnosed. This case study also helps reveal epistemic dysfunction (structural epistemic issues embedded in the healthcare system), how this relates to stigma identity-based prejudice, and how the healthcare system upholds existing societal hierarchies and disenfranchises the most vulnerable. In the modern landscape, where cases of these chronic illnesses are not only on the rise but future pandemics threaten to add to their number, this conversation is crucial for the well-being of patients and providers. This presentation will cover what epistemic injustice is and how it can be applied to the politics of the doctor-patient interaction on a micro level and the politics of the healthcare system more broadly. Contested illnesses will be explored in terms of how the “contested” label causes the patient to experience disease stigma and lowers their credibility in healthcare and across other aspects of life. This will be explored in tandem with a discussion of existing identity-based prejudice in the healthcare system and how social identities (such as those of gender, race, and socioeconomic status) intersect with the contested illness label. The effects of epistemic injustice, which include worsening patients’ symptoms of mental health and potentially disenfranchising them from the healthcare system altogether, will be presented alongside the potential ethical quandaries this poses for providers. Finally, issues with the way healthcare appointments and the modern NHS function will be explored in terms of epistemic injustice and solutions to improve doctor-patient communication and patient care will be discussed. The relationship between contested illness patients and healthcare providers is notoriously poor, and while this can mean frustration or feelings of unfulfillment in providers, the negative effects for patients are much more severe. The purpose of this research, then, is to highlight these issues and suggest ways in which to improve the healthcare experience for these patients, along with improving doctor-patient communication and mending the doctor-patient relationship in a tangible and realistic way. This research also aims to provoke important conversations about belief and hierarchy in medical settings and how these aspects intersect with identity prejudices.

Keywords: epistemic injustice, fibromyalgia, contested illnesses, chronic illnesses, doctor-patient relationships, philosophy of medicine

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Authors: Karolina Wieczorek, Sophie Wiliams

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Introduction: Patient data is often collected in Electronic Health Record Systems (EHR) for purposes such as providing care as well as reporting data. This information can be re-used to validate data models in clinical trials or in epidemiological studies. Manual validation of automated tools is vital to pick up errors in processing and to provide confidence in the output. Mentioning a disease in a discharge letter does not necessarily mean that a patient suffers from this disease. Many of them discuss a diagnostic process, different tests, or discuss whether a patient has a certain disease. The COVID-19 dataset in this study used natural language processing (NLP), an automated algorithm which extracts information related to COVID-19 symptoms, complications, and medications prescribed within the hospital. Free-text patient clinical patient notes are rich sources of information which contain patient data not captured in a structured form, hence the use of named entity recognition (NER) to capture additional information. Methods: Patient data (discharge summary letters) were exported and screened by an algorithm to pick up relevant terms related to COVID-19. Manual validation of automated tools is vital to pick up errors in processing and to provide confidence in the output. A list of 124 Systematized Nomenclature of Medicine (SNOMED) Clinical Terms has been provided in Excel with corresponding IDs. Two independent medical student researchers were provided with a dictionary of SNOMED list of terms to refer to when screening the notes. They worked on two separate datasets called "A” and "B”, respectively. Notes were screened to check if the correct term had been picked-up by the algorithm to ensure that negated terms were not picked up. Results: Its implementation in the hospital began on March 31, 2020, and the first EHR-derived extract was generated for use in an audit study on June 04, 2020. The dataset has contributed to large, priority clinical trials (including International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) by bulk upload to REDcap research databases) and local research and audit studies. Successful sharing of EHR-extracted datasets requires communicating the provenance and quality, including completeness and accuracy of this data. The results of the validation of the algorithm were the following: precision (0.907), recall (0.416), and F-score test (0.570). Percentage enhancement with NLP extracted terms compared to regular data extraction alone was low (0.3%) for relatively well-documented data such as previous medical history but higher (16.6%, 29.53%, 30.3%, 45.1%) for complications, presenting illness, chronic procedures, acute procedures respectively. Conclusions: This automated NLP algorithm is shown to be useful in facilitating patient data analysis and has the potential to be used in more large-scale clinical trials to assess potential study exclusion criteria for participants in the development of vaccines.

Keywords: automated, algorithm, NLP, COVID-19

Procedia PDF Downloads 102

Authors: X. King, E. Nazarzadeh, J. Reboud, J. Cooper

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Pulmonary diseases, such as asthma, are generally treated by the inhalation of aerosols that has the advantage of reducing the off-target (e.g., toxicity) effects associated with systemic delivery in blood. Effective respiratory drug delivery requires a droplet size distribution between 1 and 5 µm. Inhalation of aerosols with wide droplet size distribution, out of this range, results in deposition of drug in not-targeted area of the respiratory tract, introducing undesired side effects on the patient. In order to solely deliver the drug in the lower branches of the lungs and release it in a targeted manner, a control mechanism to produce the aerosolized droplets is required. To regulate the drug release and to facilitate the uptake from cells, drugs are often encapsulated into protective liposomes. However, a multistep process is required for their formation, often performed at the formulation step, therefore limiting the range of available drugs or their shelf life. Using surface acoustic waves (SAWs), a pulmonary drug delivery platform was produced, which enabled the formation of defined size aerosols and the formation of liposomes in situ. SAWs are mechanical waves, propagating along the surface of a piezoelectric substrate. They were generated using an interdigital transducer on lithium niobate with an excitation frequency of 9.6 MHz at a power of 1W. Disposable silicon superstrates were etched using photolithography and dry etch processes to create an array of cylindrical through-holes with different diameters and pitches. Superstrates were coupled with the SAW substrate through water-based gel. As the SAW propagates on the superstrate, it enables nebulisation of a lipid solution deposited onto it. The cylindrical cavities restricted the formation of large drops in the aerosol, while at the same time unilamellar liposomes were created. SAW formed liposomes showed a higher monodispersity compared to the control sample, as well as displayed, a faster production rate. To test the aerosol’s size, dynamic light scattering and laser diffraction methods were used, both showing the size control of the aerosolised particles. The use of silicon superstate with cavity size of 100-200 µm, produced an aerosol with a mean droplet size within the optimum range for pulmonary drug delivery, containing the liposomes in which the medicine could be loaded. Additionally, analysis of liposomes with Cryo-TEM showed formation of vesicles with narrow size distribution between 80-100 nm and optimal morphology in order to be used for drug delivery. Encapsulation of nucleic acids in liposomes through the developed SAW platform was also investigated. In vitro delivery of siRNA and DNA Luciferase were achieved using A549 cell line, lung carcinoma from human. In conclusion, SAW pulmonary drug delivery platform was engineered, in order to combine multiple time consuming steps (formation of liposomes, drug loading, nebulisation) into a unique platform with the aim of specifically delivering the medicament in a targeted area, reducing the drug’s side effects.

Keywords: acoustics, drug delivery, liposomes, surface acoustic waves

Procedia PDF Downloads 124

Authors: Anush Patric, M. Jadeyegowda, M. N. Ramesh, M. Ravikumar, C. R. Ajay

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Kodagu district which is situated in Central Western Ghats regions falls in one of the hottest of hot spots of biodiversity which is recognised by UNESCO. The district has one of the highest densities of community managed sacred forests in the world with rich floral and faunal diversity. It is a habitat for more than ten different types of Ethnic Indigenous tribal groups commonly called ‘Girijanas’ (Soligas, Yarvas, Jenukuruba, Bettakuruba etc.), who are having the rich knowledge of medicinal value of the plants that are commonly available in the forest. The tribal men of this region are the treasure house of the traditional plant knowledge and health care practices. An ethnobotanical survey was undertaken in tribal areas of the district to collect information about some of the indigenous medicinal plant knowledge of tribal people by semi-structured interviews, ranking exercises and field observations on their native habitat in order to evaluate the potential medicinal uses of local plants. The study revealed that, the ethnobotanical information of 83 plant species belonging to 45 families, of the total 83 species documented, most plants used in the treatment were trees (11 species), shrubs (41 species), herbs (22 species) and rarely climbers (9 species) which are used in the treatment of Hyperacidity, Respiratory disorders, Snake bite Abortifacient, Anthelmintic, Paralysis, Antiseptic, Fever, Chest pain, Stomachic, Jaundice, Piles, Asthma, Malaria, Renal disorders, Malaria and many other diseases. Maximum of 6 plant species each of Acanthaceae, Apiaceae and were used for drug preparation, followed by Asclepiadaceae, Liliaceae, Fabaceae, Verbenaceae, Caesalpinaceae, Bombaceae, Papilonaceae, Solanaceae, Rubiaceae, Myrtaceae, Amaranthaceae, Asteraceae, Ascelepidaceae, Cucurbitaceae, Apocyanaceae, and Solanaceae etc. In our present study, only medicinal plants and their local medicinal uses are recorded and presented. Information was obtained by local informants having the knowledge about medicinal plants. About 23 local tribes were interviewed. For each plant, necessary information like botanical name, family of plant species, local name and uses are given. Recent trend shows a decline in the number of traditional herbal healers in the tribal areas since the younger generation is not interested to continue this tradition. Hence, there is an urgent need to record and preserve all information on plants used by different ethnic/tribal communities for various purposes before it reaches to verge of extinction. In addition, several wild medicinal plants are declining in numbers due to deforestation and forest fires. There is need for phytochemical analysis and conservation measures to be taken for conserving medicinal plant species which is far better than allopathic medicines and these do not cause any side effects as they are the natural disease healers. So, conservation strategies have to be practiced in all levels and sectors by creating awareness about the value of such medicinal plants, and it is necessary to save the disappearing plants to strengthen the document and to conserve them for future generation.

Keywords: diseases, ethnic groups, folk medicine, Kodagu, medicinal plants

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Authors: Ashish Thakur

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This technical paper was written in view of focusing the biomaterials and its various applications in modern industries. Author tires to elaborate not only the medical, infect plenty of application in other industries. The scope of the research area covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. Biomaterials are invariably in contact with living tissues. Thus, interactions between the surface of a synthetic material and biological environment must be well understood. This paper reviews the benefits and challenges associated with surface modification of the metals in biomedical applications. The paper also elaborates how the surface characteristics of metallic biomaterials, such as surface chemistry, topography, surface charge, and wettability, influence the protein adsorption and subsequent cell behavior in terms of adhesion, proliferation, and differentiation at the biomaterial–tissue interface. The chapter also highlights various techniques required for surface modification and coating of metallic biomaterials, including physicochemical and biochemical surface treatments and calcium phosphate and oxide coatings. In this review, the attention is focused on the biomaterial-associated infections, from which the need for anti-infective biomaterials originates. Biomaterial-associated infections differ markedly for epidemiology, aetiology and severity, depending mainly on the anatomic site, on the time of biomaterial application, and on the depth of the tissues harbouring the prosthesis. Here, the diversity and complexity of the different scenarios where medical devices are currently utilised are explored, providing an overview of the emblematic applicative fields and of the requirements for anti-infective biomaterials. In addition to this, chapter introduces nanomedicine and the use of both natural and synthetic polymeric biomaterials, focuses on specific current polymeric nanomedicine applications and research, and concludes with the challenges of nanomedicine research. Infection is currently regarded as the most severe and devastating complication associated to the use of biomaterials. Osteoporosis is a worldwide disease with a very high prevalence in humans older than 50. The main clinical consequences are bone fractures, which often lead to patient disability or even death. A number of commercial biomaterials are currently used to treat osteoporotic bone fractures, but most of these have not been specifically designed for that purpose. Many drug- or cell-loaded biomaterials have been proposed in research laboratories, but very few have received approval for commercial use. Polymeric nanomaterial-based therapeutics plays a key role in the field of medicine in treatment areas such as drug delivery, tissue engineering, cancer, diabetes, and neurodegenerative diseases. Advantages in the use of polymers over other materials for nanomedicine include increased functionality, design flexibility, improved processability, and, in some cases, biocompatibility.

Keywords: nanomedicine, tissue, infections, biomaterials

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Authors: S. Kudlacik-Kramarczyk, M. Kedzierska, B. Tyliszczak

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Recently, the continuous development of medicine and related sciences has been observed. Particular emphasis is directed on the development of biomaterials, i.e., non-toxic, biocompatible and biodegradable materials that may improve the effectiveness of treatment as well as the comfort of patients. This is particularly important in the case of cancer treatment. Currently, there are many methods of cancer treatment based primarily on chemotherapy and the surgical removal of the tumor, but it is worth noting that these therapies also cause many side effects. Among women, the most common cancer is breast cancer. It may be completely cured, but the consequence of treatment is partial or complete breast mastectomy and radiation therapy, which results in severe skin burns. The skin of the patient after radiation therapy is very burned, and therefore requires intensive care and high frequency of dressing changes. The traditional dressing adheres to the burn wounds and does not absorb adequate amount of exudate from injuries and the patient is forced to change the dressing every 2 hours. Therefore, the main purpose was to develop an innovative combination of dressing material with drug carriers that may be used in anti-cancer therapy. The innovation of this solution is the combination of these two products into one system, i.e., a transdermal system with the possibility of a controlled release of the drug- cytostatic. Besides, the possibility of modifying the hydrogel matrix with aloe vera juice provides this material with new features favorable from the point of view of healing processes of burn wounds resulting from the radiation therapy. In this study, hydrogel materials containing protein spheres with the active substance have been obtained as a result of photopolymerization process. The reaction mixture consisting of the protein (albumin) spheres incorporated with cytostatic, chitosan, adequate crosslinking agent and photoinitiator has been subjected to the UV radiation for 2 minutes. Prepared materials have been subjected to the numerous studies including the analysis of cytotoxicity using murine fibroblasts L929. Analysis was conducted based on the mitochondrial activity test (MTT reduction assay) which involves the determining the number of cells characterized by proper metabolism. Hydrogel materials obtained using different amount of crosslinking agents have been subjected to the cytotoxicity analysis. According to the standards, tested material is defined as cytotoxic when the viability of cells after 24 h incubation with this material is lower than 70%. In the research, hydrogel polymer materials containing protein spheres incorporated with the active substance, i.e. a cytostatic, have been developed. Such a dressing may support the treatment of cancer due to the content of the anti-cancer drug - cytostatic, and may also provide a soothing effect on the healing of the burn wounds resulted from the radiation therapy due to the content of aloe vera juice in the hydrogel matrix. Based on the conducted cytotoxicity studies, it may be concluded that the obtained materials do not adversely affect the tested cell lines, therefore they can be subjected to more advanced analyzes.

Keywords: hydrogel polymers, cytostatics, drug carriers, cytotoxicity

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Authors: Matthew Edmunds, Andrew Hunter, Clare Littlewood, Wisha Gul, Gabriel Heppenstall-Harris, Thomas Humphries

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Background: Revision courses for medical students undertaking their final examinations are commonplace throughout the UK. Traditionally these take the form of a series of lectures over multiple weeks or a single day of intensive lectures. The COVID-19 pandemic, however, has required medical educators to create new teaching formats to ensure they adhere to social distancing requirements. It has provided an unexpected opportunity to accelerate the development of students proficiency in the use of ‘technology-enabled communication platforms’, as mandated in the 2018 GMC Outcomes of Graduates. Recent advances in technology have made distance learning possible, whilst also providing novel and more engaging learning opportunities for students. Foundation Year 2 doctors at Aintree University Hospital developed an online series of videos to help prepare medical students in the North West and byond for their final medical school examinations. Method: Eight hour-long videos covering the key topics in medicine and surgery were posted on the Peer Learning Liverpool Youtube channel. These videos were created using new technology such as the screen and audio recording platform, Loom. Each video compromised at least 20 single best answer (SBA) questions, in keeping with the format in most medical school finals. Explanations of the answers were provided, and additional important material was covered. Students were able to ask questions by commenting on the videos, with the authors replying as soon as possible. Feedback was collated using an online Google form. Results: An average of 327 people viewed each video, with 113 students filling in the feedback form. 65.5% of respondents were within one month of their final medical school examinations. The average rating for how well prepared the students felt for their finals was 6.21/10 prior to the course and 8.01/10 after the course. A paired t-test demonstrated a mean increase of 1.80 (95% CI 1.66-1.93). Overall, 98.2% said the online format worked well or very well, and 99.1% would recommend the course to a peer. Conclusions: Based on the feedback received, the online revision course was successful both in terms of preparing students for their final examinations, and with regards to how well the online format worked. Free-text qualitative feedback highlighted advantages such as; students could learn at their own pace, revisit key concepts important to them, and practice exam style questions via the case-based format. Limitations identified included inconsistent audiovisual quality, and requests for a live online Q&A session following the conclusion of the course. This course will be relaunched later in the year with increased opportunities for students to access live feedback. The success of this online course has shown the roll that technology can play in medical education. As well as providing novel teaching modes, online learning allows students to access resources that otherwise would not be available locally, and ensure that they do not miss out on teaching that was previously provided face to face, in the current climate of social distancing.

Keywords: COVID-19 pandemic, Medical School, Online learning, Revision course

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Authors: Min-Hua Wu

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The untranslatability of an established poet’s tour de force is thoroughly explored by Matthew Arnold (1822-1888). In his On Translating Homer (1861), Arnold lists the four most striking poetic qualities of Homer, namely his rapidity, plainness and directness of style and diction, plainness and directness of ideas, and nobleness. He concludes that such celebrated English translators as Cowper, Pope, Chapman, and Mr. Newman are all doomed, due to their respective failure in rendering the totality of the four Homeric poetic qualities. Why poetic translation always amounts to being proven such a mission impossible for the translator? According to Arnold, it is because there constantly exists a mist interposed between the translator’s own literary self-obsession and the objective artistic qualities that reside in the work of the original author. Foregrounding such a seemingly empowering yet actually detrimental poetic mist, he explains why the aforementioned translators fail in their attempts to bring the Homeric charm to the British reader. Drawing on Arnold’s analytical study on Homeric translation, the research attempts to bring Yu Kwang-chung the poet vis-à-vis Yu Kwang-chung the translator, with an aim not so much to find any similar mist as revealed by Arnold between his Chinese poetry and English translation as to probe into a latent and veiled literary and lingual mist interposed between Chinese and English, if not between Chinese and English literatures. The major work studied and analyzed for this study is Yu’s own Chinese poetry and his own English translation collected in The Night Watchman: Yu Kwang-chung 1958-2004. The research argues that the following critical elements that characterizes Yu’s poetics are to a certain extent 'transformed,' if not 'lost,' in his English translation: a. the Chinese pictographic and ideographic unit terms which so unfailingly characterize the poet’s incredible creativity, allowing him to habitually and conveniently coin concrete textual images or word-scapes almost at his own will; b. the subtle wordplay and punning which appear at a reasonable frequency; c. the parallel contrastive repetitive syntactic structure within a single poetic line; d. the ambiguous and highly associative diction in the adjective and noun categories; e. the literary allusion that harks back to the old times of Chinese literature; f. the alliteration that adds rhythm and smoothness to the lines; g. the rhyming patterns that bring about impressive sonority and lingering echo to the ears of the reader; h. the grandeur-imposing and sublimity-arousing word-scaping which hinges on the employment of verbs; i. the meandering cultural heritage that embraces such elements as Chinese medicine and kung fu; and j. other features of the like. Once we appeal to the Arnoldian tribunal and resort to the strict standards of such a Victorian cultural and literary critic who insists 'to see the object as in itself it really is,' we may serve as a potential judge for the tug of war between Yu Kwang-chung the poet and Yu Kwang-chung the translator, a tug of war that will not merely broaden our understating of Chinese poetics but deepen our apprehension of Chinese-English translatology.

Keywords: Yu Kwang-chung, The Night Watchman, poetry translation, Chinese-English translation, translation studies, Matthew Arnold

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Authors: Sahar El Shair, Laura Greco, William Reay, Murray Cairns

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Background: Rheumatoid arthritis (RA) is a chronic, systematic, inflammatory, autoimmune disease that involves damages to joints and erosions to the associated bones and cartilage, resulting in reduced physical function and disability. RA is a multifactorial disorder influenced by heterogenous genetic and environmental factors. Whilst different medications have proven successful in reducing inflammation associated with RA, they often come with significant side effects and limited efficacy. To address this, the novel pharmagenic enrichment score (PES) algorithm was tested in self-reported RA patients from the UK Biobank (UKBB), which is a cohort of predominantly European ancestry, and identified individuals with a high genetic risk in clinically actionable biological pathways to identify novel opportunities for precision interventions and drug repurposing to treat RA. Methods and materials: Genetic association data for rheumatoid arthritis was derived from publicly available genome-wide association studies (GWAS) summary statistics (N=97173). The PES framework exploits competitive gene set enrichment to identify pathways that are associated with RA to explore novel treatment opportunities. This data is then integrated into WebGestalt, Drug Interaction database (DGIdb) and DrugBank databases to identify existing compounds with existing use or potential for repurposed use. The PES for each of these candidates was then profiled in individuals with RA in the UKBB (Ncases = 3,719, Ncontrols = 333,160). Results A total of 209 pathways with known drug targets after multiple testing correction were identified. Several pathways, including interferon gamma signaling and TID pathway (which relates to a chaperone that modulates interferon signaling), were significantly associated with self-reported RA in the UKBB when adjusting for age, sex, assessment centre month and location, RA polygenic risk and 10 principal components. These pathways have a major role in RA pathogenesis, including autoimmune attacks against certain citrullinated proteins, synovial inflammation, and bone loss. Encouragingly, many also relate to the mechanism of action of existing RA medications. The analyses also revealed statistically significant association between RA polygenic scores and self-reported RA with individual PES scorings, highlighting the potential utility of the PES algorithm in uncovering additional genetic insights that could aid in the identification of individuals at risk for RA and provide opportunities for more targeted interventions. Conclusions In this study, pharmacologically annotated genetic risk was explored through the PES framework to overcome inter-individual heterogeneity and enable precision drug repurposing in RA. The results showed a statistically significant association between RA polygenic scores and self-reported RA and individual PES scorings for 3,719 RA patients. Interestingly, several enriched PES pathways were targeted by already approved RA drugs. In addition, the analysis revealed genetically supported drug repurposing opportunities for future treatment of RA with a relatively safe profile.

Keywords: rheumatoid arthritis, precision medicine, drug repurposing, system biology, bioinformatics

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Authors: Meitham Amereh, Mohsen Akbari, Ben Nadler

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Cancer has been recognized as one of the most challenging problems in biology and medicine. Aggressive tumors are a lethal type of cancers characterized by high genomic instability, rapid progression, invasiveness, and therapeutic resistance. Their behavior involves complicated molecular biology and consequential dynamics. Although tremendous effort has been devoted to developing therapeutic approaches, there is still a huge need for new insights into the dark aspects of tumors. As one of the key requirements in better understanding the complex behavior of tumors, mathematical modeling and continuum physics, in particular, play a pivotal role. Mathematical modeling can provide a quantitative prediction on biological processes and help interpret complicated physiological interactions in tumors microenvironment. The pathophysiology of aggressive tumors is strongly affected by the extracellular cues such as stresses produced by mechanical forces between the tumor and the host tissue. During the tumor progression, the growing mass displaces the surrounding extracellular matrix (ECM), and due to the level of tissue stiffness, stress accumulates inside the tumor. The produced stress can influence the tumor by breaking adherent junctions. During this process, the tumor stops the rapid proliferation and begins to remodel its shape to preserve the homeostatic equilibrium state. To reach this, the tumor, in turn, upregulates epithelial to mesenchymal transit-inducing transcription factors (EMT-TFs). These EMT-TFs are involved in various signaling cascades, which are often associated with tumor invasiveness and malignancy. In this work, we modeled the tumor as a growing hyperplastic mass and investigated the effects of mechanical stress from surrounding ECM on tumor invasion. The invasion is modeled as volume-preserving inelastic evolution. In this framework, principal balance laws are considered for tumor mass, linear momentum, and diffusion of nutrients. Also, mechanical interactions between the tumor and ECM is modeled using Ciarlet constitutive strain energy function, and dissipation inequality is utilized to model the volumetric growth rate. System parameters, such as rate of nutrient uptake and cell proliferation, are obtained experimentally. To validate the model, human Glioblastoma multiforme (hGBM) tumor spheroids were incorporated inside Matrigel/Alginate composite hydrogel and was injected into a microfluidic chip to mimic the tumor’s natural microenvironment. The invasion structure was analyzed by imaging the spheroid over time. Also, the expression of transcriptional factors involved in invasion was measured by immune-staining the tumor. The volumetric growth, stress distribution, and inelastic evolution of tumors were predicted by the model. Results showed that the level of invasion is in direct correlation with the level of predicted stress within the tumor. Moreover, the invasion length measured by fluorescent imaging was shown to be related to the inelastic evolution of tumors obtained by the model.

Keywords: cancer, invasion, mathematical modeling, microfluidic chip, tumor spheroids

Procedia PDF Downloads 111