Search results for: cardiovascular grafts

Authors: Ayca Bilginoglu, Belma Turan

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Metabolic syndrome, is associated impaired blood glucose level, insulin resistance, dyslipidemia caused by abdominal obesity. Also, it is related with cardiovascular risk accumulation and cardiomyopathy. The hypothesis of this study was to examine the effect of thiazolidinediones such as pioglitazone which is widely used insulin-sensitizing agents that improve glycemic control, on intracellular Na+ homeostasis in metabolic syndrome-induced cardiomyopathy in male rats. Male Wistar-Albino rats were randomly divided into three groups, namely control (Con, n=7), metabolic syndrome (MetS, n=7) and pioglitazone treated metabolic syndrome group (MetS+PGZ, n=7). Metabolic syndrome was induced by providing drinking water that was 32% sucrose, for 18 weeks. All of the animals were exposed to a 12 h light – 12 h dark cycle. Abdominal obesity and glucose intolerance had measured as a marker of metabolic syndrome. Intracellular Na+ ([Na+]i) is an important modulator of excitation–contraction coupling in heart. [Na+]i at rest and [Na+]i during pacing with electrical field stimulation in 0.2 Hz, 0.8 Hz, 2.0 Hz stimulation frequency were recorded in cardiomyocytes. Also, Na+ channel current (INa) density and I-V curve were measured to understand [Na+]i homeostasis. In results, high sucrose intake, as well as the normal daily diet, significantly increased body mass and blood glucose level of the rats in the metabolic syndrome group as compared with the non-treated control group. In MetS+PZG group, the blood glucose level and body inclined to decrease to the Con group. There was a decrease in INa density and there was a shift both activation and inactivation curve of INa. Pioglitazone reversed the shift to the control side. Basal [Na+]i either MetS and Con group were not significantly different, but there was a significantly increase in [Na+]i in stimulated cardiomyocytes in MetS group. Furthermore, pioglitazone had not effect on basal [Na+]i but it reversed the increase in [Na+]i in stimulated cardiomyocytes to the that of Con group. Results of the present study suggest that pioglitazone has a significant effect on the Na+ homeostasis in the metabolic syndrome induced cardiomyopathy in rats. All animal procedures and experiments were approved by the Animal Ethics Committee of Ankara University Faculty of Medicine (2015-2-37).

Keywords: insulin resistance, intracellular sodium, metabolic syndrome, sodium current

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Authors: Nilgün Öztürk, Hakan Sabahtin Ali, Hülya Tuba Kıyan

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The genus Chenopodium belongs to Amaranthaceae, is represented by approximately 250 species in the world and 15 species and three subspecies in Turkey. Chenopodium species are traditionally used to treat chest and abdominal pain, shortness of breath, cough and neurological disorders. Chenopodium quinoa Willd. (Quinoa) is native to Andes region of South America (especially Peru and Bolivia) and cultivated in many countries include also Turkey in the world nowadays. The seeds of quinoa are rich in protein, and the phytochemical composition consists of antioxidant substances such as polyphenolic compounds, flavonoids, vitamins, and minerals; anticancer and neuroprotective compounds such as tocotrienols; anti-inflammatory compounds such as carotenoids and anthocyanins and also saponins and starch. Food products of quinoa such as quinoa cereal bar, pasta and cornflakes are used in the diet made during many disorders like obesity, cardiovascular disorder, hypertension and Celiac disease. Also quinoa seems to have antimicrobial, anti-inflammatory and cholesterol-lowering properties because of its bioactive compounds. In this present study, the aqueous ethanolic extracts of the seeds of three different coloured genotypes of quinoa were investigated for their antioxidant activities using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, ferrous ion-chelating effect, ferric-reducing antioxidant power, ABTS radical cation decolorization assays and total phenolic contents using Folin-Ciocalteu assay. Among the three genotypes of quinoa; the aqueous ethanolic extract of the red genotype had the highest total phenolic content (83.54 ± 2.12 mg gallic acid/100 g extract) whereas the extract of the white genotype had the lowest total phenolic content (70.66 ± 0.25 mg gallic acid/100 g). According to the antioxidant activity results; the extracts showed moderate reducing power effect whereas weak ABTS radical cation decolorization and ferrous ion-chelating effect and also too weak DPPH radical scavenging activity when compared to the positive standards.

Keywords: amaranthaceae, antioxidant activity, Chenopodium quinoa willd., total phenolic content

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Authors: Gabriela D. Silva, Rodrigo L. O. R. Cunha, Mauricio D. Coutinho-Neto

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In the last four decades the biological activities of selenium compounds has received great attention, particularly for hypervalent derivates from selenium (IV) used as enzyme inhibitors. The unregulated activity of cysteine proteases are related to the development of several pathologies, such as neurological disorders, cardiovascular diseases, obesity, rheumatoid arthritis, cancer and parasitic infections. These enzymes are therefore a valuable target for designing new small molecule inhibitors such as selenuranes. Even tough there has been advances in the synthesis and design of new selenuranes based inhibitors, little is known about their mechanism of action. It is a given that inhibition occurs through the reaction between the thiol group of the enzyme and the chalcogen atom. However, several open questions remain about the nature of the mechanism (associative vs. dissociative) and about the nature of the reactive species in solution under physiological conditions. In this work we performed a theoretical investigation on model systems to study the possible routes of substitution reactions. Nucleophiles may be present in biological systems, our interest is centered in the thiol groups from the cysteine proteases and the hydroxyls from the aqueous environment. We therefore expect this study to clarify the possibility of a route reaction in two stages, the first consisting of the substitution of chloro atoms by hydroxyl groups and then replacing these hydroxyl groups per thiol groups in selenuranes. The structures of selenuranes and nucleophiles were optimized using density function theory along the B3LYP functional and a 6-311+G(d) basis set. Solvent was treated using the IEFPCM method as implemented in the Gaussian 09 code. Our results indicate that hydrolysis from water react preferably with selenuranes, and then, they are replaced by the thiol group. It show the energy values of -106,0730423 kcal/mol for dople substituition by hydroxyl group and 96,63078511 kcal/mol for thiol group. The solvatation and pH reduction promotes this route, increasing the energy value for reaction with hydroxil group to -50,75637672 kcal/mol and decreasing the energy value for thiol to 7,917767189 kcal/mol. Alternative ways were analyzed for monosubstitution (considering the competition between Cl, OH and SH groups) and they suggest the same route. Similar results were obtained for aliphatic and aromatic selenuranes studied.

Keywords: chalcogenes, computational study, cysteine proteases, enzyme inhibitors

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Authors: Angelis P. Barlampas

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The purpose of this study is to inform the reader, about the various applications of artificial intelligence (AI), in cardiac imaging. AI grows fast and its role is crucial in medical specialties, which use large amounts of digital data, that are very difficult or even impossible to be managed by human beings and especially doctors.Artificial intelligence (AI) refers to the ability of computers to mimic human cognitive function, performing tasks such as learning, problem-solving, and autonomous decision making based on digital data. Whereas AI describes the concept of using computers to mimic human cognitive tasks, machine learning (ML) describes the category of algorithms that enable most current applications described as AI. Some of the current applications of AI in cardiac imaging are the follows: Ultrasound: Automated segmentation of cardiac chambers across five common views and consequently quantify chamber volumes/mass, ascertain ejection fraction and determine longitudinal strain through speckle tracking. Determine the severity of mitral regurgitation (accuracy > 99% for every degree of severity). Identify myocardial infarction. Distinguish between Athlete’s heart and hypertrophic cardiomyopathy, as well as restrictive cardiomyopathy and constrictive pericarditis. Predict all-cause mortality. CT Reduce radiation doses. Calculate the calcium score. Diagnose coronary artery disease (CAD). Predict all-cause 5-year mortality. Predict major cardiovascular events in patients with suspected CAD. MRI Segment of cardiac structures and infarct tissue. Calculate cardiac mass and function parameters. Distinguish between patients with myocardial infarction and control subjects. It could potentially reduce costs since it would preclude the need for gadolinium-enhanced CMR. Predict 4-year survival in patients with pulmonary hypertension. Nuclear Imaging Classify normal and abnormal myocardium in CAD. Detect locations with abnormal myocardium. Predict cardiac death. ML was comparable to or better than two experienced readers in predicting the need for revascularization. AI emerge as a helpful tool in cardiac imaging and for the doctors who can not manage the overall increasing demand, in examinations such as ultrasound, computed tomography, MRI, or nuclear imaging studies.

Keywords: artificial intelligence, cardiac imaging, ultrasound, MRI, CT, nuclear medicine

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Authors: Farideh Doostan, Sahar Mohseni Taklloo, Mohammad Nosrati

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Chronic diseases are non-communicable and largely preventable by lifestyle changes including healthy diet consumption. They are the most common cause of death in the world and projected to increase by 15% globally between 2010 and 2020.The hazardous effects of behavioral and dietary risk factors on chronic disease have been established in prospective cohort studies and randomized trials. Because of some changes occur in college students’ lifestyle, assessment of dietary risk factors is important in these populations. Objective: This research was the first study that conducted to evaluate dietary intakes of Kermanian college students with WHO/FAO nutritional objectives. Material and Methods: In this descriptive cross-sectional study, 229 healthy college students of health faculty in Kerman University of Medical Sciences that do not intake any medical drugs were recruited using multistage sampling in 2013.Usual dietary intake was collected using a valid Food Frequency Questionnaire (FFQ) and diet quality was calculated based on WHO nutrient goals. To analysis of data between two groups, independent sample t. test and man whitney were applied. Results: Two hundred and twenty-nine college students; 151 females (65.9%) and 78 males (34.1%), the mean age of 21.9 years were studied. The mean of the Body Mass Index (Kg/m2) and Waist Circumference (cm) in males were 22.34 ±3.52 and 80.76±11.16 and in females were 21.19±2.62 and 73.67±7.65 respectively. Mean of daily cholesterol intake in males was significantly more than females (305±101 VS 268±98; P=0.008) and more than WHO/FAO recommendation (less than 300 mg/day). The mean of daily sodium intake in men and women were 10.4±1 and 10.9±5.3 respectively. These amounts were more than WHO/FAO recommendation (less than 2g/day). In addition, women were consumed fruit and vegetables more than men (839±336 VS 638±281; p ‹ 0.001) and these amounts were more than WHO/FAO recommendation (more than 400g/day) in both groups. Other intake indices were in the range of WHO/FAO recommendations, So that Percent of calories intake from total fat, saturated fatty acids, polyunsaturated fatty acids and added sugar were in compliance with WHO/FAO recommendations. Conclusion: Cholesterol intake in men and sodium intake in all participants were more than WHO/FAO recommendation. These dietary components are the most important causes of cardiovascular disease (one of the main causes of death in our population). These results indicated that proper nutritional education and interventions are needed in this population.

Keywords: college students, food intake, WHO /FAO nutrient intake goals, Kerman

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Authors: Sara Zelman, Courtney Meyer, Hiren Patel, Lisa Philpotts, Sue Lahey, Thomas Burke

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Background: As the global burden of disease shifts from infectious diseases to noncommunicable diseases, there is growing urgency to provide treatment for time-sensitive illnesses, such as ST-Elevation Myocardial Infarctions (STEMIs). The standard of care for STEMIs in developed countries is Percutaneous Coronary Intervention (PCI). However, this is inaccessible in resource-limited settings. Before the discovery of PCI, Streptokinase (STK) and other thrombolytic drugs were first-line treatments for STEMIs. STK has been recognized as a cost-effective and safe treatment for STEMIs; however, in settings which lack access to PCI, it has not become the established second-line therapy. A systematic literature review was conducted to geographically map the use of STK for STEMIs in resource-limited settings. Methods: Our literature review group searched the databases Cinhal, Embase, Ovid, Pubmed, Web of Science, and WHO’s Index Medicus. The search terms included ‘thrombolytics’ AND ‘myocardial infarction’ AND ‘resource-limited’ and were restricted to human studies and papers written in English. A considerable number of studies came from Latin America; however, these studies were not written in English and were excluded. The initial search yielded 3,487 articles, which was reduced to 3,196 papers after titles were screened. Three medical professionals then screened abstracts, from which 291 articles were selected for full-text review and 94 papers were chosen for final inclusion. These articles were then analyzed and mapped geographically. Results: This systematic literature review revealed that STK has been used for the treatment of STEMIs in 33 resource-limited countries, with 18 of 94 studies taking place in India. Furthermore, 13 studies occurred in Pakistan, followed by Iran (6), Sri Lanka (5), Brazil (4), China (4), and South Africa (4). Conclusion: Our systematic review revealed that STK has been used for the treatment of STEMIs in 33 resource-limited countries, with the highest utilization occurring in India. This demonstrates that even though STK has high utility for STEMI treatment in resource-limited settings, it still has not become the standard of care. Future research should investigate the barriers preventing the establishment of STK use as second-line treatment after PCI.

Keywords: cardiovascular disease, global health, resource-limited setting, ST-Elevation Myocardial Infarction, Streptokinase

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Authors: J. Nyenhuis, J. Drelich

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This research study was designed to determine if food crops could be bio-fortified with micro-nutrients by growing sprouts on mineral fortified fiber mats. Diets high in processed foods have been found to lack essential micro-nutrients for optimum human development and overall health. Some micro-nutrients such as copper (Cu) have been found to enhance the inflammatory response through its oxidative functions, thereby having a role in cardiovascular disease (CVD), metabolic syndrome (MetS), diabetes and related complications. Recycled cellulose fibers and clay saturated with micro-nutrient ions can be converted to a novel mineral-metal hybrid material in which the fiber mat becomes a carrier of essential micro-nutrients. The reduction of ionic to metallic copper was accomplished using hydrogen at temperatures ranging from 400o to 600oC. Copper particles with diameters ranging from ~1 to 400-500 nm reside on the recycled fibers that make up the mats. Seeds purchased from a commercial, organic supplier were germinated on the specially engineered cellulose fiber mats that incorporated w10 wt% clay fillers saturated with either copper particles or ionic copper. After the appearance of the first leaves, the sprouts were dehydrated and analyzed for Cu content. Nutrient analysis showed 1.5 to 1.6 increase in Cu of the sprouts grown on the fiber mats with copper particles, and 2.3 to 2.5 increase on mats with ionic copper as compared to the control samples. The antibacterial properties of materials saturated with copper ions at room temperature and at temperatures up to 400°C have been verified with halo method tests against Escherichia Coli in previous studies. E. coli is a known pathogenic risk in sprout production. Copper exhibits excellent antibacterial properties when tested on S. aureus, a pathogenic gram-positive bacterium. This has also been confirmed for the fiber-copper hybrid material in this study. This study illustrates the potential for the use of engineered mats as a viable way to increase the micro-nutrient composition of locally-grown food crops and the need for additional research to determine the uptake, nutritional implications and risks of micro-nutrient bio-fortification.

Keywords: bio-fortification, copper nutrient analysis, micro-nutrient uptake, sprouts and mineral-fortified mats

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Authors: Syrus Zimaze, George Nsimbe, Valley Mugwanya, Matiya Lule, Edgar Watson, Patrick Gwayambadde

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Physical inactivity is a growing global epidemic, also recognised as a major public health challenge. Globally, there are alarming rates of children reported with cardiovascular disease and obesity with limited interventions. In Sub Saharan Africa, there is limited information about involvement in physical activity especially among children aged 6 to 18 years. The aim of this study was to explore factors associated with involvement in physical activity among children in Uganda. Methods: We included all parents with children aged 6 to 18 years training with Excel Soccer Academy between January 2017 and June 2018. Physical activity definition was time spent participating in routine soccer training at the academy for more than 30 days. Each child's attendance was recorded, and parents provided demographic and social economic data. Data on predictors of physical activity involvement were collected using a standardized questionnaire. Descriptive statistics and frequency were used. Binary logistic regression was used at the multi variable level adjusting for education, residence, transport means and access to information technology. Results: Overall 356 parents were interviewed; Boys 318 (89.3%) engaged more in physical activity than girls. The median age for children was 13 years (IQR:6-18) and 42 years (IQR:37-49) among parents. The median time spent at the Excel soccer academy was 13.4 months (IQR: 4.6-35.7) Majority of the children attended formal education, p < 0.001). Factors associated with involvement in physical activity included: owning a permanent house compared to a rented house (odds ratio [OR] :2.84: 95% CI: 2.09-3.86, p < 0.0001), owning a car compared to using public transport (OR: 5.64 CI: 4.80-6.63, p < 0.0001), a parent having received formal education compared to non-formal education (OR: 2.93 CI: 2.47-3.46, p < 0.0001) and daily access to information technology (OR:0.40 CI:0.25-0.66, p < 0.001). Parent’s age and gender were not associated to involvement in physical activity. Conclusions: Socioeconomic factors were positively associated with involvement in physical activity with boys participating more than girls in soccer activities. More interventions are required geared towards increasing girl’s participation in physical activity and those targeting children from less privilege homes.

Keywords: physical activity, Sub-Saharan Africa, social economic factors, children

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Authors: Mohammad Javad Afroughi, Vahid Hosseini, Jason S. Olfert

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Both traffic-generated particles and noise have been associated with the development of cardiovascular diseases, especially in near-highway environments. Although noise and particulate matters (PM) have different mechanisms of dispersion, sharing the same emission source in urban areas (road traffics) can result in a similar degree of variability in their levels. This study investigated the temporal variation of and correlation between noise levels, PM concentrations and traffic intensities near a major highway in Tehran, Iran. Tehran particulate concentration is highly influenced by road traffic. Additionally, Tehran ultrafine particles (UFP, PM<0.1 µm) are mostly emitted from combustion processes of motor vehicles. This gives a high possibility of a strong association between traffic-related noise and UFP in near-highway environments of this megacity. Hourly average of equivalent continuous sound pressure level (Leq), total number concentration of UFPs, mass concentration of PM2.5 and PM10, as well as traffic count and speed were simultaneously measured over a period of three days in winter. Additionally, meteorological data including temperature, relative humidity, wind speed and direction were collected in a weather station, located 3 km from the monitoring site. Noise levels showed relatively low temporal variability in near-highway environments compared to PM concentrations. Hourly average of Leq ranged from 63.8 to 69.9 dB(A) (mean ~ 68 dB(A)), while hourly concentration of particles varied from 30,800 to 108,800 cm-3 for UFP (mean ~ 64,500 cm-3), 41 to 75 µg m-3 for PM2.5 (mean ~ 53 µg m-3), and 62 to 112 µg m-3 for PM10 (mean ~ 88 µg m-3). The Pearson correlation coefficient revealed strong relationship between noise and UFP (r ~ 0.61) overall. Under downwind conditions, UFP number concentration showed the strongest association with noise level (r ~ 0.63). The coefficient decreased to a lesser degree under upwind conditions (r ~ 0.24) due to the significant role of wind and humidity in UFP dynamics. Furthermore, PM2.5 and PM10 correlated moderately with noise (r ~ 0.52 and 0.44 respectively). In general, traffic counts were more strongly associated with noise and PM compared to traffic speeds. It was concluded that noise level combined with meteorological data can be used as a proxy to estimate PM concentrations (specifically UFP number concentration) in near-highway environments of Tehran. However, it is important to measure joint variability of noise and particles to study their health effects in epidemiological studies.

Keywords: noise, particulate matter, PM10, PM2.5, ultrafine particle

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Authors: Lito M. Amit, Venecio U. Ultra, Young-Woong Song

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The business process outsourcing (BPO) in the Philippines is expanding rapidly attracting more than 2% of total employment. Currently, the BPO industry is confronted with several issues pertaining to sustainable productivity such as meeting the staffing gap, high rate of employees’ turnover and workforce retention, and the occupational health and safety (OHS) of call center agents. We conducted a survey of OHS programs and health concerns among call center agents in the Philippines and determined the sociocultural factors that affect the vulnerability of call center agents to occupational health risks and hazards. The majority of the agents affirmed that OHS are implemented and OHS orientation and emergency procedures were conducted at employment initiations, perceived favorable and convenient working environment except for occasional noise disturbances and acoustic shock, visual, and voice fatigues. Male agents can easily adjust to the demands and changes in their work environment and flexible work schedules than female agents. Female agents have a higher tendency to be pressured and humiliated by low work performance, experience a higher incidence of emotional abuse, psychological abuse, and experience more physical stress than male agents. The majority of the call center agents had a night-shift schedule and regardless of other factors, night shift work brings higher stress to agents. While working in a call center, higher incidence of headaches and insomnia, burnout, suppressed anger, anxiety, and depressions were experienced by female, younger (21-25 years old) and those at night shift than their counterpart. Most common musculoskeletal disorders include body pain in the neck, shoulders and back; and hand and wrist disorders and these are commonly experienced by female and younger workers. About 30% experienced symptoms of cardiovascular and gastrointestinal disorders and weakened immune systems. Overall, these findings have shown the variable vulnerability by a different subpopulation of call center agents and are important in the occupational health risk prevention and management towards a sustainable human resource for BPO industry in the Philippines.

Keywords: business process outsourcing industry, health risk of call center agents, socio-cultural determinants, Philippines

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Authors: Rubai M. Ochieng

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Cancer, which accounts for 7 percent of deaths per year in Kenya, is the third highest cause of death after infectious and cardiovascular diseases. Awareness Campaigns have tended to focus on leading cancers including breast and cervical for women as well as prostrate and Esophageal for men. Consequently, less common cancers such as Acute Myeloid Leukemia (AML) are rarely properly understood by the general population and a section of the medical fraternity. Diagnoses of AML in patients who may not have heard about it sometimes results in shock, denial and confusion not just to the diagnosed, but also to their family and friends. The diagnosed and caregivers are bound to receive a lot of contradicting information about prognosis, care and treatment of AML. This information, which often comes from diverse sources including doctors, friends, internet and social media platforms, causes further confusion and panic. The situation is handled differently by different people. Religious people sometimes resort to prayer. This paper, written from the perspective of a care giver, is based on data collected from a case of Acute Myeloid Leukemia diagnosed in a 32 year old male who lost his life within six weeks of diagnosis. The sample constitutes of 16 people who participated in prayers. Out of this total, 5 were males including the diagnosed and 11 were females. All the 16 were Christians of protestant orientation including Anglicans, Quakers and Church of God members. Data was collected by the researcher herself through participant of observation. Findings discuss how the 16 participants prayed individually at different times, together in an overnight prayer meeting and every morning through a group social media platform. They shared songs and words of encouragement from the bible. The group prayed for healing, peace and strength to the diagnosed and family, financial breakthrough and doctors’ work and decisions, among other challenges that came with the situation. The paper reveals the immense benefits of prayer to the diagnosed and his close relatives and friends. They include acceptance of the condition and a positive attitude in handling the challenges that arose from the disease and treatment processes. The challenges arising from the prayer approach of handling the situation are also discussed. The paper concludes that prayer as therapy goes a long way in cancer management.

Keywords: acute myeloid leukemia, Kenya, participant observation, prayer

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Authors: Berina Pilipović, Saša Pilipović, Maja Pašić-Kulenović

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Inflammation is the body's response to impaired homeostasis caused by infection, injury or trauma resulting in systemic and local effects. Inflammation causes the body's response to injury and is characterized by a series of events including inflammatory response, response to pain receptors and the recovery process. Inflammation can be acute and chronic. The inflammatory response is described in three different phases. Free radical is an atom or molecule that has the unpaired electron and is therefore generally very reactive chemical species. Biologically important example of reaction with free radicals is called Lipid peroxidation (LP). Lipid peroxidation reactions occur in biological membranes, and if at the outset is not stopped with the action of antioxidants, it will bring damage to the membrane, which results in partial or complete loss of their physiological functions. Calcium antagonists and beta-adrenergic receptor antagonists are known drugs, and for many years and widely used in the treatment of cardiovascular diseases. Some of these compounds also show antioxidant activity. The mechanism of antioxidant activities of calcium antagonists and beta-blockers is unknown, since their structure varies widely. This research investigated the possible local anti-inflammatory activity of ointments containing 1% carvedilol in the white petrolatum USP. Ear inflammation was induced by 3% croton oil acetone solution, in quantity of 10 µl on both mouse ears. Albino Swiss mouse (n = 8) are treated with 2.5 mg/ear ointment, and control group was treated on the same way as previous with hydrocortisone 1% ointment (2.5 mg/ear). The other ear of the same animal was used as control one. Ointments were administered once per day, on the left ear. After treatment, ears were observed for three days. After three days, we measured mass (mg) of 6 mm ear punch of treated and controlled ears. The results of testing anti-inflammatory effects of ointments with carvedilol in the mouse ear model show stronger observed effect than ointment with 1% hydrocortisone in the same basis. Identical results were confirmed by the difference between the mass of 6 mm ears punch. The results were also confirmed by histological examination. Ointments with carvedilol showed significant reduction of the inflammation process caused by croton oil on the mouse inflammation model.

Keywords: antioxidant, carvedilol, inflammation, mouse ear

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Authors: H. Jeries, N. Volkova, C. G. Iglesias, M. Najjar, M. Rosenblat, M. Aviram, T. Hayek

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Background: Synthetic forms of glucocorticoids (e.g., prednisone, prednisolone) are anti-inflammatory drugs which are widely used in clinical practice. The role of glucocorticoids (GCs) in cardiovascular diseases including atherosclerosis is highly controversial, and their impact on macrophage foam cell formation is still unknown. Our aim was to investigate the effects of prednisone or its active metabolite, prednisolone, on macrophage oxidative stress and lipid metabolism using in-vivo, ex-vivo and in-vitro systems. Methods: The in-vivo study included C57BL/6 mice which were intraperitoneally injected with prednisone or prednisolone (5mg/kg) for 4 weeks, followed by lipid metabolism analyses in the mice aorta, and in peritoneal macrophages (MPM). In the ex-vivo study, we analyzed the effect of serum samples obtained from 9 healthy volunteers before or after treatment with oral prednisone (20mg for 5 days), on J774A.1 macrophage atherogenicity. In-vitro studies were conducted using J774A.1 macrophages, human monocyte derived macrophages (HMDM) and fibroblasts. Cells were incubated with increasing concentrations (0-200 ng/ml) of prednisone or prednisolone, followed by determination of cellular oxidative status, triglyceride and cholesterol metabolism. Results: Prednisone or prednisolone treatment resulted in a significant reduction in triglycerides and mainly in cholesterol cellular accumulation in MPM or in J774A.1 macrophages incubated with human serum. Similar resulted were noted in HMDM or in J774A.1 macrophages which were directly incubated with the GCs. These effects were associated with GCs inhibitory effect on triglycerides and cholesterol biosynthesis rates, throughout downregulation of diacylglycerol acyltransferase1 (DGAT1) expression, and of the sterol regulatory element binding protein (SREBP2) and HMGCR expression, respectively. In parallel to prednisone or prednisolone induced reduction in macrophage triglyceride content, paraoxonase 2 (PON2) expression was significantly upregulated. GCs-induced reduction of cellular triglyceride and cholesterol mass was mediated by the GCs receptors on macrophages since the GCs receptor antagonist (RU 486) abolished these effects. In fibroblasts, unlike macrophages, prednisone or prednisolone showed no anti-atherogenic effects. Conclusions: Prednisone or prednisolone are anti-atherogenic since they protected macrophages from lipid accumulation and foam cell formation.

Keywords: atherosclerosis, cholesterol, foam cell, macrophage, prednisone, prednisolone, triglycerides

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Authors: Leyla Sattarzadeh, Shahin Fathi Molk Kian, Maghsoud Peeri, Mohammadali Azarbaijani, Hasan Matin Homaee

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Inflammation by various mechanisms may cause atherosclerosis. Systemic circulating inflammatory markers such as C-reactive protein (CRP), pro-inflammatory cytokines such as Interleukin-6 (IL-6), vascular inflammatory markers as adhesion molecules like Intracellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1) are the predictors of cardiovascular diseases. Regarding the conflicting results about the effect of different patterns of resistance exercise training on these inflammatory markers, present study aimed to examine the effect of different patterns of eight week resistance exercise training on CRP, IL-6, ICAM-1 and VCAM-1 levels in healthy untrained women. 56 healthy volunteered untrained female university students (aged: 21 ± 3 yr., Body Mass Index: 21.5 ± 3.5 kg/m²) were selected purposefully and divided into four groups. At the end of training protocol and after subject drop during the protocol, upper body exercise training (n=11), lower body (n=12) and whole body resistance exercise training group (n=11) completed the eight weeks of training period although the control group (n=7) did anything. Blood samples gathered pre and post-experimental period and CRP, IL-6, ICAM-1 and VCAM-1 levels were evaluated using special laboratory kits, then the difference of pre and post values of each indices analyzed using one-way analysis of variance (α < 0.05). The results of one way ANOVA for difference of pre and post values of CRP, ICAM-1 and VCAM-1 showed no significant changes due to the exercise training, but there were significant differences between groups about IL-6. Tukey post- hoc test indicated that there is significant difference between the differences of pre and post values of IL-6 between lower body exercise training group and control group, and eight weeks of lower body exercise training lead to significant changes in IL-6 values. There were no changes in anthropometric indices. The findings show that the different patterns of upper, lower and whole body exercise training by involving the different amounts of muscles altered the IL-6 values in lower body exercise training group probably because of engaging the bigger amount of muscles, but showed any significant changes about CRP, ICAM-1 and VCAM-1 probably due to intensity and duration of exercise or the lower levels of these markers at baseline of healthy people.

Keywords: resistance training, C-reactive protein, interleukin-6, intracellular adhesion molecule-1, vascular cell adhesion molecule-1

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Authors: Amrit Vasdev, Edwin Rho, Gurinder Vasdev

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Robotic surgery has enabled a new spectrum of minimally invasive breast reconstruction by improving visualization, surgeon posturing, and improved patient outcomes.1 The DaVinci robot system can be utilized in nipple sparing mastectomies and reconstructions. The process involves the insufflation of the subglandular space and a dissection of the mammary gland with a combination of cautery and blunt dissection. This case outlines a 35-year-old woman who has a long-standing family history of breast cancer and a diagnosis of a deleterious BRCA2 genetic mutation. She has decided to proceed with bilateral nipple sparing mastectomies with implants. Her perioperative mammogram and MRI were negative for masses, however, her left internal mammary lymph node was enlarged. She has taken oral contraceptive pills for 3-5 years and denies DES exposure, radiation therapy, human replacement therapy, or prior breast surgery. She does not smoke and rarely consumes alcohol. During the procedure, the patient received a standardized anesthetic for out-patient surgery of propofol infusion, succinylcholine, sevoflurane, and fentanyl. Aprepitant was given as an antiemetic and preoperative Tylenol and gabapentin for pain management. Concerns for the patient during the procedure included CO2 insufflation into the subcutaneous space. With CO2 insufflation, there is a potential for rapid uptake leading to severe acidosis, embolism, and subcutaneous emphysema.2To mitigate this, it is important to hyperventilate the patient and reduce both the insufflation pressure and the CO2 flow rate to the minimal acceptable by the surgeon. For intraoperative monitoring during this 6-9 hour long procedure, it has been suggested to utilize an Arterial-Line for end-tidal CO2 monitoring. However, in this case, it was not necessary as the patient had excellent cardiovascular reserve, and end-tidal CO2 was within normal limits for the duration of the procedure. A BIS monitor was also utilized to reduce anesthesia burden and to facilitate a prompt discharge from the PACU. Minimal Invasive Robotic Surgery will continue to evolve, and anesthesiologists need to be prepared for the new challenges ahead. Based on our limit number of patients, robotic mastectomy appears to be a safe alternative to open surgery with the promise of clearer tissue demarcation and better cosmetic results.

Keywords: anesthesia, mastectomies, robotic, hypercarbia

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Authors: Mustafa M. Donma, Ayşen Haksayar, Bahadır Batar, Buse Tepe, Birol Topçu, Orkide Donma

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Childhood obesity is an ever-increasing health problem. The Association of obesity with severe chronic diseases such as diabetes and cardiovascular diseases makes the problem life-threatening. Aside from psychological, societal and metabolic factors, genetic polymorphisms have gained importance concerning etiology in recent years. The aim of this study was to evaluate the relationship between rs10455872 gene polymorphism in the Lipoprotein (a) locus and the development of childhood obesity. This was a prospective study carried out according to the Helsinki Declarations. The study protocol was approved by the Institutional Ethics Committee. This study was supported by Tekirdag Namik Kemal University Rectorate, Scientific Research Projects Coordination Unit. Project No: NKUBAP.02.TU.20.278. A total of 180 children (103 obese (OB) and 77 healthy), aged 6-18 years, without any acute or chronic disease, participated in the study. Two different groups were created: OB and healthy control. Each group was divided into two further groups depending on the nature of the polymorphism. Anthropometric measurements were taken during the detailed physical examination. Laboratory tests and TANITA measurements were performed. For the statistical evaluations, SPSS version 28.0 was used. A P-value smaller than 0.05 was the statistical significance degree. The distribution of lipoprotein (a) rs10455872 gene polymorphism did not differ between OB and healthy children. Children with AG genotype in both OB and control groups had lower body mass index (BMI), diagnostic obesity notation model assessment index (DONMA II), body fat ratio (BFR), C-reactive protein (CRP), and metabolic syndrome index (MetS index) values compared to children with normal AA genotype. In the OB group, serum iron, vitamin B12, hemoglobin, MCV, and MCH values were found to be higher in the AG genotype group than those of children with the normal AA genotype. A significant correlation was found between the MetS index and BFR among OB children with normal homozygous genotype. MetS index increased as BFR increased in this group. However, such a correlation was not observed in the OB group with heterozygous AG genotype. To the best of our knowledge, the association of lipoprotein (a) rs10455872 gene polymorphism with the etiology of childhood obesity has not been studied yet. Therefore, this study was the first report suggesting polymorphism with AG genotype as a good risk factor for obesity.

Keywords: child, gene polymorphism, lipoprotein (a), obesity, rs10455872

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Authors: Laura M. Hovsepyan, Gayane S. Ghazaryan, Hasmik V. Zanginyan

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Hypertension (HD) is the most common cardiovascular pathology that causes disability and mortality in the working population. Most often, heart failure (HF), which is based on myocardial remodeling, leads to death in hypertension. Recently, endothelial dysfunction (EDF) or a violation of the functional state of the vascular endothelium has been assigned a significant role in the structural changes in the myocardium and the occurrence of heart failure in patients with hypertension. It has now been established that tissues affected by inflammation form increased amounts of superoxide radical and NO, which play a significant role in the development and pathogenesis of various pathologies. They mediate inflammation, modify proteins and damage nucleic acids. The aim of this work was to study the processes of oxidative modification of proteins (OMP) and the production of nitric oxide in hypertension. In the experimental work, the blood of 30 donors and 33 patients with hypertension was used. For the quantitative determination of OMP products, the based on the reaction of the interaction of oxidized amino acid residues of proteins and 2,4-dinitrophenylhydrazine (DNPH) with the formation of 2,4-dinitrophenylhydrazones, the amount of which was determined spectrophotometrically. The optical density of the formed carbonyl derivatives of dinitrophenylhydrazones was recorded at different wavelengths: 356 nm - aliphatic ketone dinitrophenylhydrazones (KDNPH) of neutral character; 370 nm - aliphatic aldehyde dinirophenylhydrazones (ADNPH) of neutral character; 430 nm - aliphatic KDNFG of the main character; 530 nm - basic aliphatic ADNPH. Nitric oxide was determined by photometry using Grace's solution. Adsorption was measured on a Thermo Scientific Evolution 201 SF at a wavelength of 546 nm. Thus, the results of the studies showed that in patients with arterial hypertension, an increased level of nitric oxide in the blood serum is observed, and there is also a tendency to an increase in the intensity of oxidative modification of proteins at a wavelength of 270 nm and 363 nm, which indicates a statistically significant increase in aliphatic aldehyde and ketone dinitrophenylhydrazones. The increase in the intensity of oxidative modification of blood plasma proteins in the studied patients, revealed by us, actually reflects the general direction of free radical processes and, in particular, the oxidation of proteins throughout the body. A decrease in the activity of the antioxidant system also leads to a violation of protein metabolism. The most important consequence of the oxidative modification of proteins is the inactivation of enzymes.

Keywords: hypertension (HD), oxidative modification of proteins (OMP), nitric oxide (NO), oxidative stress

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Authors: Vivek Kumar Gupta, Kripi Vohra, Monika Gupta

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Pulses have been a vital ingredient of the balanced human diet in India. Lentil (Lens culinaris Medikus or Lens esculenta Moench.) is a common legume known since biblical times. Lentil seeds, with or without hulls, are cooked as dhal and this has been the main dish for millennia in the South Asian region. Oxidative stress can damage lipids, proteins, enzymes, carbohydrates and DNA in cells and tissues, resulting in membrane damage, fragmentation or random cross linking of molecules like DNA, enzymes and structural proteins and even lead to cell death induced by DNA fragmentation and lipid peroxidation. These consequences of oxidative stress construct the molecular basis in the development of cancer, neurodegenerative disorders, cardiovascular diseases, diabetes and autoimmune. The aim of the present work is to assess the antioxidant potential of the peteroleum ether, acetone, methanol and water extract of the Lens esculenta seeds. In vitro antioxidant assessment of the extracts was carried out using 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging activity, hydroxyl radical scavenging activity, reducing power assay. The quantitative estimation of total phenolic content, total flavonoid content in extracts and in plant material, total saponin content, total alkaloid content, crude fibre content, total volatile content, fat content and mucilage content in drug material was also carried out. Though all the extracts exhibited dose dependent reducing power activity the acetone extract was found to possess significant hydrogen donating ability in DPPH (45.83%-93.13%) and hydroxyl radical scavenging system (28.7%-46.41%) than the peteroleum ether, methanol and water extracts. Total phenolic content in the acetone and methanol extract was found to be 608 and 188 mg gallic acid equivalent of phenol/g of sample respectively. Total flavonoid content of acetone and methanol extract was found to be 128 and 30.6 mg quercetin equivalent/g of sample respectively. It is evident that acetone extract of Lentil seeds possess high levels of polyphenolics and flavonoids that could be utilized as antioxidants and neutraceuticals.

Keywords: antioxidant, flavanoids, Lens esculenta, polyphenols

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Authors: Manali Jain, Neeta Singh, Raunaq Fatima, Soniya Nityanand, Mandakini Pradhan, Chandra Prakash Chaturvedi

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Isolated Congenital Heart Defect (ICHD) is the major cause of neonatal death worldwide among all forms of CHDs. A significant proportion of fetuses with ICHD die in the neonatal period if no treatment is provided. Recently, stem cell therapies have emerged as a potential approach to ameliorate ICHD in children. ICHD is characterized by cardiac structural abnormalities during embryogenesis due to alterations in the cardiomyogenic properties of a pool of cardiac progenitors/ stem cells associated with fetal heart development. The stem cells present in the amniotic fluid (AF) are of fetal origin and may reflect the physiological and pathological changes in the fetus during embryogenesis. Therefore, in the present study, the cardiomyogenic potential of AF-MSCs derived from fetuses with ICHD (ICHD AF-MSCs) has been evaluated and compared with that of AF-MSCs of structurally normal fetuses (normal AF-MSCs). Normal and ICHD AF-MSC were analyzed for the expression of cardiac progenitor markers viz., stage-specific embryonic antigen-1 (SSEA-1), vascular endothelial growth factor 2 (VEGFR-2) and platelet-derived growth factor receptor-alpha (PDGFR-α) by flow cytometry. The immunophenotypic characterization revealed that ICHD AF-MSCs have significantly lower expression of cardiac progenitor markers VEGFR-2 (0.14% ± 0.6 vs.48.80% ± 0.9; p <0.01), SSEA-1 (70.86% ± 2.4 vs. 88.36% ±2.7; p <0.01), and PDGFR-α (3.92% ± 1.8 vs. 47.59% ± 3.09; p <0.01) in comparison to normal AF-MSCs. Upon induction with 5’-azacytidine for 21 days, ICHD AF-MSCs showed a significantly down-regulated expression of cardiac transcription factors such as GATA-4 (0.4 ± 0.1 vs. 6.8 ± 1.2; p<0.01), ISL-1 (2.3± 0.6 vs. 14.3 ± 1.12; p<0.01), NK-x 2-5 (1.1 ± 0.3 vs. 14.1 ±2.8; p<0.01), TBX-5 (0.4 ± 0.07 vs. 4.4 ± 0.3; p<0.001), and TBX-18 (1.3 ± 0.2 vs. 4.19 ± 0.3; p<0.01) when compared with the normal AF-MSCs. Furthermore, immunocytochemical staining revealed that both types of AF-MSCs could differentiate into cardiovascular lineages and express cardiomyogenic, endothelial, and smooth muscle actin markers, viz., cardiac troponin (cTNT), CD31, and alpha-smooth muscle actin (α-SMA). However, normal AF-MSCs showed an enhanced expression of cTNT (p<0.001), CD31 (p<0.01), and α-SMA (p<0.05), compared to ICHD AF-MSCs. Overall, these results suggest that the ICHD-AF-MSCs have a defective cardiomyogenic differentiation potential and that the defects in these stem cells may have a role in the pathogenesis of ICHD.

Keywords: amniotic fluid, cardiomyogenic potential, isolated congenital heart defect, mesenchymal stem cells

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Authors: Christine Y. Yeh, Brian D. Piening, Sarah M. Totten, Kimberly Kukurba, Wenyu Zhou, Kevin P. F. Contrepois, Gucci J. Gu, Sharon Pitteri, Michael Snyder

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Three million deaths worldwide are attributed to obesity. However, the biomolecular mechanisms that describe the link between adiposity and subsequent disease states are poorly understood. Insulin resistance characterizes approximately half of obese individuals and is a major cause of obesity-mediated diseases such as Type II diabetes, hypertension and other cardiovascular diseases. This study makes use of longitudinal quantitative and high-throughput multi-omics (genomics, epigenomics, transcriptomics, glycoproteomics etc.) methodologies on blood samples to develop multigenic and multi-analyte signatures associated with weight gain and insulin resistance. Participants of this study underwent a 30-day period of weight gain via excessive caloric intake followed by a 60-day period of restricted dieting and return to baseline weight. Blood samples were taken at three different time points per patient: baseline, peak-weight and post weight loss. Patients were characterized as either insulin resistant (IR) or insulin sensitive (IS) before having their samples processed via longitudinal multi-omic technologies. This comparative study revealed a wealth of biomolecular changes associated with weight gain after using methods in machine learning, clustering, network analysis etc. Pathways of interest included those involved in lipid remodeling, acute inflammatory response and glucose metabolism. Some of these biomolecules returned to baseline levels as the patient returned to normal weight whilst some remained elevated. IR patients exhibited key differences in inflammatory response regulation in comparison to IS patients at all time points. These signatures suggest differential metabolism and inflammatory pathways between IR and IS patients. Biomolecular differences associated with weight gain and insulin resistance were identified on various levels: in gene expression, epigenetic change, transcriptional regulation and glycosylation. This study was not only able to contribute to new biology that could be of use in preventing or predicting obesity-mediated diseases, but also matured novel biomedical informatics technologies to produce and process data on many comprehensive omics levels.

Keywords: insulin resistance, multi-omics, next generation sequencing, proteogenomics, type ii diabetes

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Authors: Ashti Morovati, Hushyar Azari, Bahram Pourghassem Gargari

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Objectives and goals: The prevalence of metabolic syndrome (MetS), as a major health burden for societies, is increasing. This clinical trial was conducted to evaluate the effects of CuEO supplementation on anthropometric indices, systolic and diastolic blood pressure, blood glucose level, insulin resistance and serum lipid level in patients suffering from MetS. Methods: This was a randomized, triple‐blind, placebo‐controlled clinical trial in which 56 patients with MetS aged 18–60 years who fulfilled the eligibility criteria were randomly allocated to an intervention or a control group. Inclusion criteria for the study were comprised of diagnosis of MetS according to the new International Federation of Diabetes. The exclusion criteria were defined as: taking herbal supplements, use of drugs having evident interaction with cumin such as anti‐depressant drugs, vitamin D, omega 3, selenium, zinc, smoking, pregnancy, or breastfeeding, suffering from cancer, having any history of gastrointestinal and hepatic, cardiovascular, thyroid and kidney disorders, and menopause. 75 mg CuEO or placebo soft gels were administered three times daily to the participants for eight weeks. The soft gel consumption was checked by asking the participants to bring the medication containers in the follow‐up visits at the 4th and the 8th weeks of the study. Data pertaining to blood pressure, height, weight, waist circumference, hip circumference and BMI, as well as food consumption were collected at the beginning and end of the study. Fasting blood samples ( glucose, triglyceride, total cholesterol, HDL-cholesterol and LDL-cholesterol) were obtained and biochemical measurements were assessed at the beginning and end of the study. Results: At eight weeks, a total of 44 patients completed this study. Except for diastolic blood pressure (DBP), the other assessed variables were not significantly different between the two groups. In intra group analysis, placebo and CuEO groups both had insignificant decrements in DBP (mean difference [MD] with 95% CI: −3.31 [−7.11, 0.47] and −1.77 [−5.95, 2.40] mmHg, respectively). However, DBP was significantly lower in CuEO compared with the placebo group at the end of study (81.41 ± 5.88 vs. 84.09 ± 5.54 mmHg, MD with 95% CI: −3.98 [−7.60, −0.35] mmHg, p < .05). Conclusions: The results of this study indicated that CuEO does not have any effect on MetS components, except for DBP in patients with MetS.

Keywords: blood pressure, fasting blood glucose, lipid profile, waist circumference

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Authors: Amy Stringer, Resa Chandler

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

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

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Authors: Suraj Sam Issaka, Anita Asamoah, Abass Gibrilla, Joseph Richmond Fianko

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Polycyclic aromatic hydrocarbons (PAHs) are a group of organic compounds that can form in edible oils during repeated frying and accumulate in fried foods. This study assesses the chances of health risks (carcinogenic and non-carcinogenic) due to PAHs levels in popular finger foods (bean cakes, plantain chips, doughnuts) fried in edible oils (mixed vegetable, sunflower, soybean) from the Ghanaian market. Employing probabilistic health risk assessment that considers variability and uncertainty in exposure and risk estimates provides a more realistic representation of potential health risks. Monte Carlo simulations with 10,000 iterations were used to estimate carcinogenic, mutagenic, and non-carcinogenic risks for different age groups (A: 6-10 years, B: 11-20 years, C: 20-70 years), food types (bean cake, plantain chips, doughnut), oil types (soybean, mixed vegetable, sunflower), and re-usage frying oil frequencies (once, twice, thrice). Our results suggest that, for age Group A, doughnuts posed the highest probability of carcinogenic risk (91.55%) exceeding the acceptable threshold, followed by bean cakes (43.87%) and plantain chips (7.72%), as well as the highest probability of unacceptable mutagenic risk (89.2%), followed by bean cakes (40.32%). Among age Group B, doughnuts again had the highest probability of exceeding carcinogenic risk limits (51.16%) and mutagenic risk limits (44.27%). At the same time, plantain chips exhibited the highest maximum carcinogenic risk. For adults age Group C, bean cakes had the highest probability of unacceptable carcinogenic (50.88%) and mutagenic risks (46.44%), though plantain chips showed the highest maximum values for both carcinogenic and mutagenic risks in this age group. Also, on non-carcinogenic risks across different age groups, it was found that age Group A) who consumed doughnuts had a 68.16% probability of a hazard quotient (HQ) greater than 1, suggesting potential cognitive impairment and lower IQ scores due to early PAH exposure. This group also faced risks from consuming plantain chips and bean cake. For age Group B, the consumption of plantain chips was associated with a 36.98% probability of HQ greater than 1, indicating a potential risk of reduced lung function. In age Group C, the consumption of plantain chips was linked to a 35.70% probability of HQ greater than 1, suggesting a potential risk of cardiovascular diseases.

Keywords: PAHs, fried foods, carcinogenic risk, non-carcinogenic risk, Monte Carlo simulations

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Authors: Sharat Chandra, Zilong Wang, Ru-Rong Ji, Andrey Bortsov

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Chronic pain (CP) therapeutic approaches have limited efficacy. As a result, doctors are prescribing opioids for chronic pain, leading to opioid overuse, abuse, and addiction epidemic. Therefore, the development of effective and safe CP drugs remains an unmet medical need. Voltage-gated sodium (Nav) channels act as cardiovascular and neurological disorder’s molecular targets. Nav channels selective inhibitors are hard to design because there are nine closely-related isoforms (Nav1.1-1.9) that share the protein sequence segments. We are targeting the Nav1.7 found in the peripheral nervous system and engaged in the perception of pain. The objective of this project was to screen a 1.5 million compound library for identification of inhibitors for Nav1.7 with analgesic effect. In this study, we designed a protocol for identification of isoform-selective inhibitors of Nav1.7, by utilizing the prior information on isoform-selective antagonists. First, a similarity search was performed; then the identified hits were docked into a binding site on the fourth voltage-sensor domain (VSD4) of Nav1.7. We used the FTrees tool for similarity searching and library generation; the generated library was docked in the VSD4 domain binding site using FlexX and compounds were shortlisted using a FlexX score and SeeSAR hyde scoring. Finally, the top 25 compounds were tested with molecular dynamics simulation (MDS). We reduced our list to 9 compounds based on the MDS root mean square deviation plot and obtained them from a vendor for in vitro and in vivo validation. Whole-cell patch-clamp recordings in HEK-293 cells and dorsal root ganglion neurons were conducted. We used patch pipettes to record transient Na⁺ currents. One of the compounds reduced the peak sodium currents in Nav1.7-HEK-293 stable cell line in a dose-dependent manner, with IC50 values at 0.74 µM. In summary, our computer-aided analgesic discovery approach allowed us to develop pre-clinical analgesic candidate with significant reduction of time and cost.

Keywords: chronic pain, voltage-gated sodium channel, isoform-selective antagonist, similarity search, virtual screening, analgesics development

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Authors: Amanda Sheard, Garry Lee, Katherine Stockham

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Introduction: Health benefits associated with wine consumption have been well documented; these include anticancer, anti-inflammatory, and cardiovascular protection. The majority of these health benefits have been linked to polyphenols found within wine and grapes. Once consumed polyphenols exhibit free radical quenching capabilities. Environmental factors such as rainfall, temperature, CO2 levels and sunlight exposure have been shown to affect the polyphenol content of grapes. The objective of this work was to evaluate the effect of growing conditions on the antioxidant capacity of grapes obtained from a single plot vineyard in Perth. This was achieved through the analysis of samples using; oxygen radical antioxidant capacity (ORAC), cellular antioxidant activity (CAA) in human red blood cells, ICP-MS and ICP-OES, total polyphenols (PP’s), and total flavonoid’s (FLa). The data obtained was compared to observed climate data. The 14 Selected Vitis Vinefera L. cultivars included Cabernet franc, Cabernet Sauvignon, Carnelian, Chardonnay, Grenache, Melbec, Merlot, Orange muscat, Rousanne, Sauvignon Blanc, Shiraz, Tempernillo, Verdelho, and Voignier. Results: Notable variation’s between cultivars included results ranging from 125 mg/100 g-350 mg/100 g for PP’s, 93 mg/100 g–300 mg/100 g for FLa, 13 mM T.E/kg–33 mM T.E/kg for ORAC and 0.3 mM Q.E/kg–27 mM Q.E/kg CAA were found between red and white grape cultivars. No correlation was found between CAA and the ORAC obtained in this study; except that white cultivars were consistently lower than red. ICP analysis showed that seeds contained the highest concentration of copper followed by skins and flesh of the grape. A positive correlation between copper and ORAC was found. The ORAC, PP’s, and FLa in red grapes were consistently higher than white grape cultivars; these findings were supported by literature values. Significance: The cellular antioxidant activities of white and red wine cultivars were used to compare the bioactivity of these grapes against the chemical ORAC measurement. The common method of antioxidant activity measurement is the chemical value from ORAC analysis; however this may not reflect the activity within the human body. Hence, the measurements were also carried out using the cellular antioxidant activity to perform a comparison. Additionally, the study explored the influence of weather systems such as El Niño and La Niña on the polyphenol content of Australian wine cultivars grown in Perth.

Keywords: oxygen radical antioxidant activity, cellular antioxidant activity, total polyphenols, total flavonoids, wine grapes, climate

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Authors: S. Somerset, D. J. Hoare

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Participation in sport is linked to better mental and physical health in children and adults. Studies have shown children who participate in sports benefit from improved social skills, self-confidence, communication skills and a better quality of life. Children who participate in sports from a young age are also more likely to continue to have active lifestyles during adulthood. This is an important consideration with a nation where physical activity levels are declining and the incidences of obesity are rising. Getting children active and keeping them active can provide long term health benefits to the individual but also a potential reduction in health costs in the future. This systematic review aims to identify the barriers to participation in sport for children aged up to 18 years and encompasses both qualitative and quantitative studies. The bibliographic databases, EMBASE, Medline, CINAHL and SportDiscus were searched. Additional hand searches were carried out on review articles found in the searches to identify any studies that may have been missed. Studies involving children up to 18 years without additional needs focusing on barriers to participation in sport were included. Randomised control trials, policy guidelines, studies with sport as an intervention, studies focusing on the female athlete triad, tobacco abuse, alcohol abuse, drug abuse, pre exercise testing, and cardiovascular disease were excluded. Abstract review, full paper review and quality appraisal were conducted by two researchers. A consensus meeting took place to resolve any differences at the abstract, full text and data extraction / quality appraisal stages. The CASP qualitative studies appraisal tool and the CASP cohort studies tool (excluding question 3 and 4 which refer to interventions) were used for quality appraisal in this review. The review identified several salient barriers to participation in sport for children. These barriers ranged from the uniform worn during school physical education lessons to the weather during participation in sport. The most commonly identified barriers in the review include parental support, time allocation, location of the activity and the cost of the activity. Therefore, it would be beneficial for a greater provision to be made within the school environment for children to participate sport. This can reduce the cost and time commitment required from parents to encourage participation. This would help to increase activity levels of children, which ultimately can only be a good thing.

Keywords: barrier, children, participation, sport

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Authors: Mengistu G. Woldu, Hani Y. Zaki, Areeg Faggad, Badreldin E. Abdalla

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Background: Type 2 diabetes mellitus (T2DM) is a complex, degenerative, and multi-factorial disease, which is culpable for huge mortality and morbidity worldwide. Even though relatively significant numbers of studies are conducted on the genetics domain of this disease in the developed world, there is huge information gap in the sub-Saharan Africa region in general and in Eritrea in particular. Objective: The principal aim of this study was to investigate the association of common variants of the Insulin Receptor Substrate 1 (IRS1) and Transcription Factor 7-Like 2 (TCF7L2) genes with T2DM in the Eritrean population. Method: In this cross-sectional case control study 200 T2DM patients and 112 non-diabetes subjects were participated and genotyping of the IRS1 (rs13431179, rs16822615, 16822644rs, rs1801123) and TCF7L2 (rs7092484) tag SNPs were carries out using PCR-RFLP method of analysis. Haplotype analyses were carried out using Plink version 1.07, and Haploview 4.2 software. Linkage disequilibrium (LD), and Hardy-Weinberg equilibrium (HWE) analyses were performed using the Plink software. All descriptive statistical data analyses were carried out using SPSS (Version-20) software. Throughout the analysis p-value ≤0.05 was considered statistically significant. Result: Significant association was found between rs13431179 SNP of the IRS1 gene and T2DM under the recessive model of inheritance (OR=9.00, 95%CI=1.17-69.07, p=0.035), and marginally significant association found in the genotypic model (OR=7.50, 95%CI=0.94-60.06, p=0.058). The rs7092484 SNP of the TCF7L2 gene also showed markedly significant association with T2DM in the recessive (OR=3.61, 95%CI=1.70-7.67, p=0.001); and allelic (OR=1.80, 95%CI=1.23-2.62, p=0.002) models. Moreover, eight haplotypes of the IRS1 gene found to have significant association withT2DM (p=0.013 to 0.049). Assessments made on the interactions of genotypes of the rs13431179 and rs7092484 SNPs with various parameters demonstrated that high density lipoprotein (HDL), low density lipoprotein (LDL), waist circumference (WC), and systolic blood pressure (SBP) are the best T2DM onset predicting models. Furthermore, genotypes of the rs7092484 SNP showed significant association with various atherogenic indexes (Atherogenic index of plasma, LDL/HDL, and CHLO/HDL); and Eritreans carrying the GG or GA genotypes were predicted to be more susceptible to cardiovascular diseases onset. Conclusions: Results of this study suggest that IRS1 (rs13431179) and TCF7L2 (rs7092484) gene polymorphisms are associated with increased risk of T2DM in Eritreans.

Keywords: IRS1, SNP, TCF7L2, type 2 diabetes

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Authors: Mompi Sharma, Labananda Choudhury, Anjana M. Saikia

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Background: The period life table is entirely based on the assumption that the mortality patterns of the population existing in the given period will persist throughout their lives. However, it has been observed that the mortality rate continues to decline. As such, if the rates of change of probabilities of death are considered in a life table then we get a dynamic life table. Although, mortality has been declining in all parts of India, one may be interested to know whether these declines had appeared more in an urban area of underdeveloped regions like North-Eastern India. So, attempt has been made to know the mortality pattern and the life expectancy under dynamic scenario in Guwahati, the biggest city of North Eastern India. Further, if the probabilities of death changes then there is a possibility that its different constituent probabilities will also change. Since cardiovascular disease (CVD) is the leading cause of death in Guwahati. Therefore, an attempt has also been made to formulate dynamic cause specific death ratio and probabilities of death due to CVD. Objectives: To construct dynamic life table for Guwahati for the year 2011 based on the rates of change of probabilities of death over the previous 10 and 25 years (i.e.,2001 and 1986) and to compute corresponding dynamic cause specific death ratio and probabilities of death due to CVD. Methodology and Data: The study uses the method proposed by Denton and Spencer (2011) to construct dynamic life table for Guwahati. So, the data from the Office of the Birth and Death, Guwahati Municipal Corporation for the years 1986, 2001 and 2011 are taken. The population based data are taken from 2001 and 2011 census (India). However, the population data for 1986 has been estimated. Also, the cause of death ratio and probabilities of death due to CVD are computed for the aforementioned years and then extended to dynamic set up for the year 2011 by considering the rates of change of those probabilities over the previous 10 and 25 years. Findings: The dynamic life expectancy at birth (LEB) for Guwahati is found to be higher than the corresponding values in the period table by 3.28 (5.65) years for males and 8.30 (6.37) years for females during the period of 10 (25) years. The life expectancies under dynamic consideration in all the other age groups are also seen higher than the usual life expectancies, which may be possible due to gradual decline in probabilities of death since 1986-2011. Further, a continuous decline has also been observed in death ratio due to CVD along with cause specific probabilities of death for both sexes. As a consequence, dynamic cause of death probability due to CVD is found to be less in comparison to usual procedure. Conclusion: Since incorporation of changing mortality rates in period life table for Guwahati resulted in higher life expectancies and lower probabilities of death due to CVD, this would possibly bring out the real situation of deaths prevailing in the city.

Keywords: cause specific death ratio, cause specific probabilities of death, dynamic, life expectancy

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Authors: Oladele V. Adeniyi, B. Longo-Mbenza, Daniel T. Goon

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Background: Lipids are often low or in the normal ranges and controversial in the atherogenesis among Black Africans. The effect of the severity of obesity on some traditional and novel cardiovascular disease risk factors is unclear before and after a diet and exercise maintenance programme among obese black South Africans with type 2 diabetes mellitus (T2DM). Therefore, this study aimed to identify the risk factors to discriminate obesity classes among patients with T2DM before and after a diet and exercise programme. Methods: This interventional cohort of Black South Africans with T2DM was followed by a very – low calorie diet and exercise programme in Mthatha, between August and November 2013. Gender, age, and the levels of body mass index (BMI), blood pressure, monthly income, daily frequency of meals, blood random plasma glucose (RPG), serum creatinine, total cholesterol (TC), triglycerides (TG), LDL –C, HDL – C, Non-HDL, ratios of TC/HDL, TG/HDL, and LDL/HDL were recorded. Univariate analysis (ANOVA) and multivariate discriminant analysis were performed to separate obesity classes: normal weight (BMI = 18.5 – 24.9 kg/m2), overweight (BMI = 25 – 29.9 kg/m2), obesity Class 1 (BMI = 30 – 34.9 kg/m2), obesity Class 2 (BMI = 35 – 39.9 kg/m2), and obesity Class 3 (BMI ≥ 40 kg/m2). Results: At the baseline (1st Month September), all 327 patients were overweight/obese: 19.6% overweight, 42.8% obese class 1, 22.3% obese class 2, and 15.3% obese class 3. In discriminant analysis, only systolic blood pressure (SBP with positive association) and LDL/HDL ratio (negative association) significantly separated increasing obesity classes. At the post – evaluation (3rd Month November), out of all 327 patients, 19.9%, 19.3%, 37.6%, 15%, and 8.3% had normal weight, overweight, obesity class 1, obesity class 2, and obesity class 3, respectively. There was a significant negative association between serum creatinine and increase in BMI. In discriminant analysis, only age (positive association), SBP (U – shaped relationship), monthly income (inverted U – shaped association), daily frequency of meals (positive association), and LDL/HDL ratio (positive association) classified significantly increasing obesity classes. Conclusion: There is an epidemic of diabesity (Obesity + T2DM) in this Black South Africans with some weight loss. Further studies are needed to understand positive or negative linear correlations and paradoxical curvilinear correlations between these markers and increase in BMI among black South African T2DM patients.

Keywords: atherogenic dyslipidaemia, dietary interventions, obesity, south africans

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Authors: Orkide Donma, Mustafa M. Donma

Abstract:

Obesity may lead to growing serious health problems throughout the world. Vitamin D appears to play a role in cardiovascular and metabolic health. Vitamin D deficiency may add to derangements in human metabolic systems, particularly those of children. Childhood obesity is associated with an increased risk of chronic and sophisticated diseases. The aim of this study is to investigate associations as well as possible differences related to parameters affected by obesity and their relations with vitamin D status in obese (OB) and morbid obese (MO) children. This study included a total of 78 children. Of them, 41 and 37 were OB and MO, respectively. WHO BMI-for age percentiles were used for the classification of obesity. The values above 99 percentile were defined as MO. Those between 95 and 99 percentiles were included into OB group. Anthropometric measurements were recorded. Basal metabolic rates (BMRs) were measured. Vitamin D status is determined by the measurement of 25-hydroxy cholecalciferol [25- hydroxyvitamin D3, 25(OH)D] using high-performance liquid chromatography. Vitamin D status was evaluated as deficient, insufficient and sufficient. Values < 20.0 ng/ml, values between 20-30 ng/ml and values > 30.0 ng/ml were defined as vitamin D deficient, insufficient and sufficient, respectively. Optimal 25(OH)D level was defined as ≥ 30 ng/ml. SPSSx statistical package program was used for the evaluation of the data. The statistical significance degree was accepted as p < 0.05. Mean ages did not differ between the groups. Significantly increased body mass index (BMI), waist circumference (C) and neck C as well as significantly decreased fasting blood glucose (FBG) and vitamin D values were observed in MO group (p < 0.05). In OB group, 37.5% of the children were vitamin D deficient, and in MO group the corresponding value was 53.6%. No difference between the groups in terms of lipid profile, systolic blood pressure (SBP), diastolic blood pressure (DBP) and insulin values was noted. There was a severe statistical significance between FBG values of the groups (p < 0.001). Important correlations between BMI, waist C, hip C, neck C and both SBP as well as DBP were found in OB group. In MO group, correlations only with SBP were obtained. In a similar manner, in OB group, correlations were detected between SBP-BMR and DBP-BMR. However, in MO children, BMR correlated only with SBP. The associations of vitamin D with anthropometric indices as well as some lipid parameters were defined. In OB group BMI, waist C, hip C and triglycerides (TRG) were negatively correlated with vitamin D concentrations whereas none of them were detected in MO group. Vitamin D deficiency may contribute to the complications associated with childhood obesity. Loss of correlations between obesity indices-DBP, vitamin D-TRG, as well as relatively lower FBG values, observed in MO group point out that the emergence of MetS components starts during obesity state just before the transition to morbid obesity. Aside from its deficiency state, associations of vitamin D with anthropometric measurements, blood pressures and TRG should also be evaluated before the development of morbid obesity.

Keywords: children, morbid obesity, obesity, vitamin D

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