Search results for: Newcastle disease virus

Authors: Sevde Altuntas, Fatih Buyukserin

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Alzheimer’s disease is responsible for irreversible neural damage of brain parts. One of the disease markers is Amyloid-β 1-42 protein that accumulates in the brain in the form plaques. The basic problem for detection of the protein is the low amount of protein that cannot be detected properly in body liquids such as blood, saliva or urine. To solve this problem, tests like ELISA or PCR are proposed which are expensive, require specialized personnel and can contain complex protocols. Therefore, Surface-enhanced Raman Spectroscopy (SERS) a good candidate for detection of Amyloid-β 1-42 protein. Because the spectroscopic technique can potentially allow even single molecule detection from liquid and solid surfaces. Besides SERS signal can be improved by using nanopattern surface and also is specific to molecules. In this context, our study proposes to fabricate diagnostic test models that utilize Au-coated nanopatterned polycarbonate (PC) surfaces modified with Thioflavin - T to detect low concentrations of Amyloid-β 1-42 protein in water and artificial saliva medium by the enhancement of protein SERS signal. The nanopatterned PC surface that was used to enhance SERS signal was fabricated by using Anodic Alumina Membranes (AAM) as a template. It is possible to produce AAMs with different column structures and varying thicknesses depending on voltage and anodization time. After fabrication process, the pore diameter of AAMs can be arranged with dilute acid solution treatment. In this study, two different columns structures were prepared. After a surface modification to decrease their surface energy, AAMs were treated with PC solution. Following the solvent evaporation, nanopatterned PC films with tunable pillared structures were peeled off from the membrane surface. The PC film was then modified with Au and Thioflavin-T for the detection of Amyloid-β 1-42 protein. The protein detection studies were conducted first in water via this biosensor platform. Same measurements were conducted in artificial saliva to detect the presence of Amyloid Amyloid-β 1-42 protein. SEM, SERS and contact angle measurements were carried out for the characterization of different surfaces and further demonstration of the protein attachment. SERS enhancement factor calculations were also completed via experimental results. As a result, our research group fabricated diagnostic test models that utilize Au-coated nanopatterned polycarbonate (PC) surfaces modified with Thioflavin-T to detect low concentrations of Alzheimer’s Amiloid – β protein in water and artificial saliva medium. This work was supported by The Scientific and Technological Research Council of Turkey (TUBITAK) Grant No: 214Z167.

Keywords: alzheimer, anodic aluminum oxide, nanotopography, surface enhanced Raman spectroscopy

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Authors: Minakshi Mainaji Sonawane, Bharti W. Gawali, Sudhir Mendhekar, Ramesh R. Manza

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People's lives and health are severely impacted by skin diseases. A new study proposes an effective method for identifying the different forms of skin diseases. Image denoising is a technique for improving image quality after it has been harmed by noise. The proposed technique is based on the usage of the wavelet transform. Wavelet transform is the best method for analyzing the image due to the ability to split the image into the sub-band, which has been used to estimate the noise ratio at the noisy image. According to experimental results, the proposed method presents the best values for MSE, PSNR, and Entropy for denoised images. we can found in Also, by using different types of wavelet transform filters is make the proposed approach can obtain the best results 23.13, 20.08, 50.7 for the image denoising process

Keywords: MSE, PSNR, entropy, Gaussian filter, DWT

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Authors: Aliya Sekenova, Vyacheslav Ogay

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The derivation of human induced pluripotent stem cells (iPSCs) from somatic cells by direct reprogramming opens wide perspectives in the regenerative medicine. It means the possibility to develop the personal and, consequently, any immunologically compatible cells for applications in cell-based therapy. The purpose of our study was to develop the technology for the production of NK cells from T cell-derived induced pluripotent stem cells (TiPSCs) for subsequent application in adoptive cancer immunotherapy. Methods: In this study iPSCs were derived from peripheral blood T cells using Sendai virus vectors expressing Oct4, Sox2, Klf4 and c-Myc. Pluripotent characteristics of TiPSCs were examined and confirmed with alkaline phosphatase staining, immunocytochemistry and RT-PCR analysis. For NK cell differentiation, embryoid bodies (EB) formed from (TiPSCs) were cultured in xenogeneic serum-free medium containing human serum, IL-3, IL-7, IL-15, SCF, FLT3L without using M210-B4 and AFT-024 stromal feeder cells. After differentiation, NK cells were characterized with immunofluorescence analysis, flow cytometry and cytotoxicity assay. Results: Here, we for the first time demonstrate that TiPSCs can effectively differentiate into functionally active NK cells without M210-B4 and AFT-024 xenogeneic stroma cells. Immunofluorescence and flow cytometry analysis showed that EB-derived cells can differentiate into a homogeneous population of NK cell expressing high levels of CD56, CD45 and CD16 specific markers. Moreover, these cells significantly express killing activation receptors such as NKp44 and NKp46. In the comparative analysis, we observed that NK cells derived using feeder-free culture system have more high killing activity against K-562 tumor cells, than NK cells derived by feeder-dependent method. Thus, we think that our obtained data will be useful for the development of large-scale production of NK cells for translation into cancer immunotherapy.

Keywords: induced pluripotent stem cells, NK cells, T cells, cell diffentiation, feeder cell-free culture system

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Authors: Mihai Palade, Gina Cecilia Pistol, Mariana Stancu, Veronica Chedea, Ionelia Taranu

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Nutrition is an important determinant of general health status, with especially focus on prevention and/or attenuation of the inflammatory-associated pathologies. People with chronic kidney disease can experience chronic inflammation that can lead to cardiovascular disease and even an increased rate of death. There are important links between chronic kidney diseases, inflammation and nutritional strategies that may prevent or protect against undesirable inflammation and oxidative stress. The grape by-products either seeds or pomace are rich in polyphenols which may be beneficial in prevention of inflammatory, antioxidant and antimicrobial processes. As a model for studying the impact of grape seeds on renal inflammation and oxidative stress, we used in this study weaned piglets. After a feeding trial of 30 days with a control diet and an experimental diet containing 5% grape seed (GS), kidney samples were collected. In renal tissues were determined the expression and activity of important markers of immune respose and oxidative stress: pro-inflammatory cytokines (TNF-alpha, IL-1 beta, IL-6, IL-8, IFN-gamma), anti-inflammatory cytokines (IL-4, IL-10), anti-oxidant enzymes (catalase CAT, superoxide dismutase SOD, glutathione peroxidise GPx) and important mediators belonging to nuclear receptors (NF-kB1, Nrf-2 and PPAR-gamma). Gene expression was evaluated by qPCR, whereas protein concentration was determined using proteomic techniques (ELISA). The activity of anti-oxidant enzymes was determined using specific kits. Our results showed that GS enriched in polyphenols does not have effect on TNF-alpha, IL-6 and IL-1 beta gene expression and protein concentration in kidney. By contrast, the gene expression and protein level of IL-8 and IFN-gamma were decreased in GS kidney. Anti-inflammatory cytokines IL-4 and IL-10 gene levels were increased in kidneys collected from GS piglets in comparison with controls, with no modification of protein levels between the two groups. The activities of anti-oxidant enzymes CAT and GPx were increased in kidney by GS, whereas SOD activity was unmodified in comparison with control samples. Also, the GS diet was associated with no modulation of mRNAs for nuclear receptors NF-kB1, Nrf-2 and PPAR-gamma gene expressions in kidneys. In conclusion, our results demonstrated that GS enriched in bioactive compounds such polyphenols could modulate inflammation and oxidative stress markers in kidney tissues. Further studies are necessary to elucidate the mechanism of action of GS compounds in case kidney inflammation associated with oxidative stress, and signalling molecules involved in these mechanisms.

Keywords: animal model, kidney inflammation, oxidative stress, grape seed

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Authors: Zeb Hussain, Muhammad Asif Qureshi, Shaheen Sharafat

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Background: Measles is a contagious viral infection common in childhood. Vaccination against measles is included in the expanded program of immunization (EPI). However, and alarmingly, a high mortality rate is observed due to measles infection in Pakistan. Moreover a recent outbreak of measles in various areas of Pakistan further highlights the problem. It is therefore important to investigate measles specific IgG (antibody) levels in our population. Objective: To quantify measles specific IgG antibodies amongst vaccinated children in district Qamber Shahdadkot, Sindh. Methodology: This cross-sectional study was conducted at the Microbiology section of the Dow-Diagnostic-Research-and-Reference-Laboratory (DDRRL), DUHS after Institutional Review Board approval (IRB-516/DUHS/-14) during August-December-2014. A total of 173 participants (residents of district Qamber Shahdadkot, Sindh) aged between 1-5 years were recruited in the study. Blood samples were collected as per standard phlebotomy guidelines. Blood was stored at 4 °C overnight. Samples were subsequently spun at a speed of 10000rpm to separate sera, which were divided into small aliquots to be frozen at -20 °C. Frozen sera were transported to the DDRRL on dry ice. Measles specific IgG (antibody) titers were quantified using enzyme linked immunosorbant assay (ELISA). Results: Blood was collected from a total of 173 individuals ranging between 1-5 years of age. Of these, a total of 88 participants were males and 85 were females. Of the 173 investigated samples, only 53 (30.6%) showed protective IgG titers against measles while 120 (69%) were sero-negative. Measles specific IgG antibodies titers were higher in female participants compared to the males. Conclusion: Our data demonstrate that a substantial percentage of vaccinated children in district Qamber-Shahdadkot did not have protective antibody titres against measles. It is therefore extremely important to investigate measles specific IgG levels in various parts of Pakistan in order to implement appropriate protective measures.

Keywords: sero-surveillance, measles, vaccinated children, Pakistan

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Authors: Hassina Harkat, Samiha Taybe, Salima Loucif, Valérie Beneteau, Patrick Pale

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Indole and its derivatives have attracted great interest because of their importance in the synthetic organic and medicinal chemistry. They are widely used as anti hypertension, anti tubercular, anticancer activity, antiviral, Alzheimer's disease, antioxidant properties, and free radical induced lipid peroxidation. Many drugs and natural products contain indole moiety, such as the vinca alkaloids, fungal metabolites and marine natural products. Generally applicable synthetic methods for indole moiety involve ring closure to form the pyrrole. Indole derivatives can also be accessed by further functionalization of the indole nucleus. Therefore we report a mild and efficient protocol for the synthesis of analogues of indole catalyzed via zeolithe USY doped with CuI under solvent-free conditions.

Keywords: indole, zeolithe, USY-CuI, heterogeneous catalysis

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Authors: Tassana Boontong, Vilaivan Thongcharoen, Orapan Thosingha, Suphamon Chansakul, Anorut Jenwitheesuk, Chanin Chakkrapopyodhin, Isara Phiwchai, Mattika Chaichan, Rungnapha Khiewchaum

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According to Thailand health policy, subdistrict health promoting hospitals (SHPHs) serve as forefront facilities for inclusive health care service. Those services include health promotion, disease prevention, primary medical care and rehabilitation. However, SHPHs residing in some distant area, such as SHPHs residing on the islands, would deliver different services relevant to health needs of the local people and the tourists. This research aimed to study health care delivery services at SHPHs on the islands in Thailand. Data were collected using questionnaires. The result revealed that in Thailand, there are 58 SHPHs on the islands. During data collection process, the researchers were not allowed to collect data in 5 SHPHs in the southern part due to Covid-19 pandemic. The report is based on 53 SHPHs on the islands. Numbers of health care personnel were 201, 72.14 % were female, with the ages ranged from 22 to 60 years (mean = 35.56 years). About 53% were community health personnel, while 26.08% were professional nurses. In regard to work experiences, the range of year varied from less than 1 year to 30 years, with the mean of 8.36 years. The majority of their responsibilities focused on providing primary medical care (86.34%), caring of people with chronic illnesses (85.30%) and providing medical care procedures for patients with chronic illnesses at home (84.36%). Nurses were main health care personnel in performing primary medical care. Due to difficulty transportation from the islands to the mainland, nurses had to provide prompt emergency medical care while the patients arrived with emergency and critical illnesses such as severe head trauma, stroke or coronary artery disease. Although some medical procedures were complex and not covered by nursing and midwifery license, they decided to protect patients from life- threatening conditions and make them stable before transportation. In SHPHs, the workload exceeded manpower, health care personnel had to work overtime almost every day. In the famous tourist islands, health care personnel had to carry 3-4 folds of their workload during the holidays because of the large crowds of foreign and Thai tourists. It is recommended that SHPHs on the islands should scale up the level of services to cover advanced medical care. Health care personnel, in particular, professional nurses, should be equipped with emergency and critical care skills. The expected outcomes of the services should emphasize on rescuing patients with emergency and life-threatening illnesses and providing comprehensive care for people living on or visiting the islands.

Keywords: distant area, islands, sub district health promoting hospital, heath care services, Thailand

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Authors: Mutaz Shurahabeel Ahmed Ombada

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This paper investigates potential health and financial settlement of health information technology, this paper evaluates health care with the use of IT and other associated industries. It assesses prospective savings and costs of extensive acceptance of Electronic Medical Record Systems (EMRS), models significant to health as well as safety remuneration, and conclude that efficient EMRS execution and networking could ultimately save more than US $55 billion annually through recuperating health care effectiveness and that Health Information Technology -enabled prevention and administration of chronic disease could eventually double those savings while rising health and other social remuneration. On the contrary, this is improbable to be realized without related to significant modifications to the health care system.

Keywords: electronic medical record systems, health care economics, EMRS

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Authors: Chitsanzo Isaac

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Across the world, the ongoing Covid-19 pandemic has challenged urban systems and policy frameworks, highlighting societal vulnerabilities and systemic inequities among many communities. Measures of confinement and social distancing to contain the Covid-19 virus have fragmented the physical and social fabric of cities. This has caused urban dwellers to reassess how they engage with their urban surroundings and maintain social ties. Urbanists have presented strategies that would allow communities to survive and even thrive, in extraordinary times of crisis like the pandemic. Tactical Urbanism, particularly the 15-Minute City, has gained popularity. It is considered a resilient approach in the global north, however, it’s transferability to the global south has been called into question. To this end, this paper poses the question: to what extent is the 15-Minute City framework integral sustainable design, and are there processes that make it adoptable by cities in the global south? This paper explores four issues using secondary quantitative data analysis and convergence analysis in the Paris and Blantyre urban regions. First, it questions how the 15-Minute City has been defined and measured, and how it impacts urban dwellers. Second, it examines the extent to which the 15-minute city performs under the lens of frameworks such as Wilber’s integral theory and Fleming’s integral sustainable design theory. Thirdly this work examines the processes that can be transferred to developing cities which foster community resilience through the perspectives of experience, behaviors, cultures, and systems. Finally, it reviews the principal ways in which a multi-perspective reality can be the basis for resilient community design and sustainable urban development. This work will shed a light on the importance of a multi-perspective reality as a means of achieving sustainable urban design goals in developing urban areas.

Keywords: 15-minute city, developing cities, global south, community resilience, integral sustainable design, systems thinking, complexity, tactical urbanism

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Authors: Muhammad Qamar Masood, Syed Abbas Raza, Umar Yousaf Raja, Imran Hassan, Bilal Afzal, Muhammad Aleem Zahir, Atika Shaheer

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Background: Cardiovascular disease (CVD) is a major burden among people with type 2 diabetes (T2D) with 1 in 3 reported to have CVD. Therefore, understanding real-world clinical characteristics and prescribing patterns could help in better care. Objective: The CONVERGE (Cardiovascular Outcomes and Value in the Real world with GLP-1RAs) study characterized demographics and medication usage patterns in T2D intensified (add-on to metformin) overall population. The data were further divided into subgroups {dipeptidyl peptidase-4 inhibitors (DPP-4is), sulfonylureas (SUs), insulins, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is)}, according to the latest prescribed antidiabetic agent (ADA) in India/Pakistan/Thailand. Here, we report findings from Pakistan. Methods: A multi-center retrospective study utilized data from medical records between 13-Sep-2008 (post-market approval of GLP-1RAs) and 31-Dec-2017 in adults (≥18-year-old). The data for this study were collected from 05 centers / institutes located in major cities of Pakistan, including Karachi, Lahore, Islamabad, and Multan. These centers included National Hospital, Aga Khan University Hospital, Diabetes Endocrine Clinic Lahore, Shifa International Hospital, Mukhtar A Sheikh Hospital Multan. Data were collected at start of medical record and at 6 or 12-months prior to baseline based on variable type; analyzed descriptively. Results: Overall, 1,010 patients were eligible. At baseline, overall mean age (SD) was 51.6 (11.3) years, T2D duration was 2.4 (2.6) years, HbA1c was 8.3% (1.9) and 35% received ≥1CVD medications in the past 1-year (before baseline). Most frequently prescribed ADAs post-metformin were DPP-4is and SUs (~63%). Only 6.5% received GLP-1RAs and SGLT-2is were not available in Pakistan during the study period. Overall, it took a mean of 4.4 years and 5 years to initiate GLP-1RAs and SGLT-2is, respectively. In comparison to other subgroups, more patients from GLP-1RAs received ≥3 types of ADA (58%), ≥1 CVD medication (64%) and had higher body mass index (37kg/m2). Conclusions: Utilization of GLP-1RAs and SGLT-2is was low, took longer time to initiate and not before trying multiple ADAs. This may be due to lack of evidence for CV benefits for these agents during the study period. The planned phase 2 of the CONVERGE study can provide more insights into utilization and barriers to prescribe GLP-1RAs and SGLT-2is post 2018 in Pakistan.

Keywords: type 2 diabetes, GLP-1RA, treatment intensification, cardiovascular disease

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Authors: Sukryool Kang, James McConnaughey, Robin Doroshow, Raj Shekhar

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Still’s murmur, a vibratory heart murmur, is the most common normal innocent murmur of childhood. Many children with this murmur are unnecessarily referred for cardiology consultation and testing, which exacts a high cost financially and emotionally on the patients and their parents. Pediatricians to date are not successful at distinguishing Still’s murmur from murmurs of true heart disease. In this paper, we present a new algorithmic approach to distinguish Still’s murmur from pathological murmurs in children. We propose two distinct features, spectral width and signal power, which describe the sharpness of the spectrum and the signal intensity of the murmur, respectively. Seventy pediatric heart sound recordings of 41 Still’s and 29 pathological murmurs were used to develop and evaluate our algorithm that achieved a true positive rate of 97% and false positive rate of 0%. This approach would meet clinical standards in recognizing Still’s murmur.

Keywords: AR modeling, auscultation, heart murmurs, Still's murmur

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Authors: Ruswanto Ruswanto, Richa Mardianingrum, Tita Nofianti, Nur Rahayuningsih

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Tuberculosis (TB) is a chronic disease as a result of Mycobacterium tuberculosis. It can affect all age groups, and hence, is a global health problem that causes the death of millions of people every year. One of the drugs used in tuberculosis treatment is isonicotinohydrazide. In this study, N'-benzoylisonicotinohydrazide derivative compounds (a-l) were prepared using acylation reactions between isonicotinohydrazide and benzoyl chloride derivatives, through the reflux method. Molecular docking studies suggested that all of the compounds had better interaction with Mycobacterium tuberculosis enoyl-acyl carrier protein reductase (InhA) than isonicotinohydrazide. It can be concluded that N'-benzoylisonicotinohydrazide derivatives (a-l) could be used as anti-tuberculosis candidates. From the docking results revealed that all of the compounds interact well with InhA, with compound g (N'-(3-nitrobenzoyl)isonicotinohydrazide) exhibiting the best interaction.

Keywords: anti-tuberculosis , docking, InhA, N'-benzoylisonicotinohydrazide, synthesis

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Authors: Robert Krause

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

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

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Authors: Orkide Donma, Mustafa M. Donma

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Obesity, a disease associated with a low-grade inflammation, is a risk factor for the development of metabolic syndrome (MetS). So far, MetS risk factors such as parameters related to glucose and lipid metabolisms as well as blood pressure were considered for the evaluation of this disease. There are still some ambiguities related to the characteristic features of MetS observed particularly in pediatric population. Hormonal imbalance is also important, and quite a lot information exists about the behaviour of some hormones in adults. However, the hormonal profiles in pediatric metabolism have not been cleared yet. The aim of this study is to investigate the profiles of cortisol, insulin, and thyroid hormones in children with MetS. The study population was composed of morbid obese (MO) children without (Group 1) and with (Group 2) MetS components. WHO BMI-for age and sex percentiles were used for the classification of obesity. The values above 99 percentile were defined as morbid obesity. Components of MetS (central obesity, glucose intolerance, high blood pressure, high triacylglycerol levels, low levels of high density lipoprotein cholesterol) were determined. Anthropometric measurements were performed. Ratios as well as obesity indices were calculated. Insulin, cortisol, thyroid stimulating hormone (TSH), free T₃ and free T₄ analyses were performed by electrochemiluminescence immunoassay. Data were evaluated by statistical package for social sciences program. p<0.05 was accepted as the degree for statistical significance. The mean ages±SD values of Group 1 and Group 2 were 9.9±3.1 years and 10.8±3.2 years, respectively. Body mass index (BMI) values were calculated as 27.4±5.9 kg/m² and 30.6±8.1 kg/m², successively. There were no statistically significant differences between the ages and BMI values of the groups. Insulin levels were statistically significantly increased in MetS in comparison with the levels measured in MO children. There was not any difference between MO children and those with MetS in terms of cortisol, T₃, T₄ and TSH. However, T₄ levels were positively correlated with cortisol and negatively correlated with insulin. None of these correlations were observed in MO children. Cortisol levels in both MO as well as MetS group were significantly correlated. Cortisol, insulin, and thyroid hormones are essential for life. Cortisol, called the control system for hormones, orchestrates the performance of other key hormones. It seems to establish a connection between hormone imbalance and inflammation. During an inflammatory state, more cortisol is produced to fight inflammation. High cortisol levels prevent the conversion of the inactive form of the thyroid hormone T₄ into active form T₃. Insulin is reduced due to low thyroid hormone. T₃, which is essential for blood sugar control- requires cortisol levels within the normal range. Positive association of T₄ with cortisol and negative association of it with insulin are the indicators of such a delicate balance among these hormones also in children with MetS.

Keywords: children, cortisol, insulin, metabolic syndrome, thyroid hormones

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Authors: Deepa, Yashbir Singh, Shi Yi Wu, Michael Friebe, Joao Manuel R. S. Tavares, Hu Wei-Chih

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Cardiovascular disease can be detected by measuring the regional and global wall motion of the left ventricle (LV) of the heart; In this study, we designed a dynamic simulation tool using Computed Tomography (CT) images to assess the difference between actual and simulated left ventricular functions. Thirteen healthy subjects were involved in the study with actual and simulated left ventricular functions. In this research, we found the high correlation between actual left ventricular wall motion and simulated left ventricular wall motion. Our results confirm that our simulation tool is feasible for simulating left ventricular motion.

Keywords: cardiac imaging, left-ventricular remodeling, cardiac wall motion, myocardial functions

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Authors: Arash Jafari, Somaye Bahrami, Mohammad Hossein Razi Jalali

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Dicrocoeliosis, caused by Dicrocoelium dendriticum is a hepatic parasitic disease of clinical and financial significance in ruminant breeding, which causes direct losses due to condemnation of parasitized livers. The purpose of our study was to assess the effects of natural dicrocoeliosis on the antioxidant defense capability of the liver in sheep. For this purpose, livers of 40 infected sheep with D. dendriticumalong with livers of 20 healthy (control) sheep were collected from animals slaughtered in Khuzestan province, Iran. An increase in malondialdehyde concentrations accompanied by decreased activities of SOD and GPX of infected liver was noticed when com-pared with control values. Our data indicate that through dicrocoeliosis insufficient scavenging of reactive oxygen species takes place and caused oxidative liver damage.

Keywords: Dicrocoelium dendriticum, lipid peroxidation, antioxidant enzyme, liver

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Authors: David Gottlieb, Jason Yoder

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The feeling of loneliness is not uncommon in modern society, and yet, there is a fundamental lack of understanding in its origins and purpose in nature. One interpretation of loneliness is that it is a subjective experience that punishes a lack of social behavior, and thus its emergence in human evolution is seemingly tied to the survival of early human tribes. Still, a common counterintuitive response to loneliness is a state of hypervigilance, resulting in social withdrawal, which may appear maladaptive to modern society. So far, no computational model of loneliness’ effect during evolution yet exists; however, agent-based models (ABM) can be used to investigate social behavior, and applying evolution to agents’ behaviors can demonstrate selective advantages for particular behaviors. We propose an ABM where each agent contains four social behaviors, and one goal-seeking behavior, letting evolution select the best behavioral patterns for resource allocation. In our paper, we use an algorithm similar to the boid model to guide the behavior of agents, but expand the set of rules that govern their behavior. While we use cohesion, separation, and alignment for simple social movement, our expanded model adds goal-oriented behavior, which is inspired by particle swarm optimization, such that agents move relative to their personal best position. Since agents are given the ability to form connections by interacting with each other, our final behavior guides agent movement toward its social connections. Finally, we introduce a mechanism to represent a state of loneliness, which engages when an agent's perceived social involvement does not meet its expected social involvement. This enables us to investigate a minimal model of loneliness, and using evolution we attempt to elucidate its value in human survival. Agents are placed in an environment in which they must acquire resources, as their fitness is based on the total resource collected. With these rules in place, we are able to run evolution under various conditions, including resource-rich environments, and when disease is present. Our simulations indicate that there is strong selection pressure for social behavior under circumstances where there is a clear discrepancy between initial resource locations, and against social behavior when disease is present, mirroring hypervigilance. This not only provides an explanation for the emergence of loneliness, but also reflects the diversity of response to loneliness in the real world. In addition, there is evidence of a richness of social behavior when loneliness was present. By introducing just two resource locations, we observed a divergence in social motivation after agents became lonely, where one agent learned to move to the other, who was in a better resource position. The results and ongoing work from this project show that it is possible to glean insight into the evolutionary advantages of even simple mechanisms of loneliness. The model we developed has produced unexpected results and has led to more questions, such as the impact loneliness would have at a larger scale, or the effect of creating a set of rules governing interaction beyond adjacency.

Keywords: agent-based, behavior, evolution, loneliness, social

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Authors: Sergio Alejandro Cuevas, Catherine Etchebest, Fernando Luis Barroso Da Silva

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The flavivirus genus has several organisms responsible for generating various diseases in humans. Special in Brazil, Zika (ZIKV), Dengue (DENV) and Yellow Fever (YFV) viruses have raised great health concerns due to the high number of cases affecting the area during the last years. Diagnostic is still a difficult issue since the clinical symptoms are highly similar. The understanding of their common structural/dynamical and biomolecular interactions features and differences might suggest alternative strategies towards differential serological diagnostics and therapeutic intervention. Due to their immunogenicity, the primary focus of this study was on the ZIKV, DENV and YFV non-structural proteins 1 (NS1) protein. By means of computational studies, we calculated the main physical chemical properties of this protein from different strains that are directly responsible for the biomolecular interactions and, therefore, can be related to the differential infectivity of the strains. We also mapped the electrostatic differences at both the sequence and structural levels for the strains from Uganda to Brazil that could suggest possible molecular mechanisms for the increase of the virulence of ZIKV. It is interesting to note that despite the small changes in the protein sequence due to the high sequence identity among the studied strains, the electrostatic properties are strongly impacted by the pH which also impact on their biomolecular interactions with partners and, consequently, the molecular viral biology. African and Asian strains are distinguishable. Exploring the interfaces used by NS1 to self-associate in different oligomeric states, and to interact with membranes and the antibody, we could map the strategy used by the ZIKV during its evolutionary process. This indicates possible molecular mechanisms that can explain the different immunological response. By the comparison with the known antibody structure available for the West Nile virus, we demonstrated that the antibody would have difficulties to neutralize the NS1 from the Brazilian strain. The present study also opens up perspectives to computationally design high specificity antibodies.

Keywords: zika, biomolecular interactions, electrostatic interactions, molecular mechanisms

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Authors: Takaaki Nemoto

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Case presentation: A 69-year-old Japanese man presented with a low-grade fever and fatigue that had persisted for one month. The patient had an aortic dissection on the aortic arch 13 years prior, an abdominal aortic aneurysm seven years prior, and an aortic dissection on the distal aortic arch one year prior, which were all treated with artificial blood-vessel replacement surgery. Laboratory tests revealed an inflammatory response (CRP 7.61 mg/dl), high serum creatinine (Cr 1.4 mg/dL), and elevated transaminase (AST 47 IU/L, ALT 45 IU/L). The patient was admitted to our hospital on suspicion of prosthetic vascular graft infection. Following further workups on the inflammatory response, an enhanced chest computed tomography (CT) and a non-enhanced chest DWI (MRI) were performed. The patient was diagnosed with a pulmonary fistula and a prosthetic vascular graft infection on the distal aortic arch. After admission, the patient was administered Ceftriaxion and Vancomycine for 10 days, but his fever and inflammatory response did not improve. On day 13 of hospitalization, a lung fistula repair surgery and an omental filling operation were performed, and Meropenem and Vancomycine were administered. The fever and inflammatory response continued, and therefore we took repeated blood cultures. M. fortuitum was detected in a blood culture on day 16 of hospitalization. As a result, we changed the treatment regimen to Amikacin (400 mg/day), Meropenem (2 g/day), and Cefmetazole (4 g/day), and the fever and inflammatory response began to decrease gradually. We performed a test of sensitivity for Mycobacterium fortuitum, and found that the MIC was low for fluoroquinolone antibacterial agent. The clinical course was good, and the patient was discharged after a total of 8 weeks of intravenous drug administration. At discharge, we changed the treatment regimen to Levofloxacin (500 mg/day) and Clarithromycin (800 mg/day), and prescribed these two drugs as a long life suppressive therapy. Discussion: There are few cases of prosthetic vascular graft infection caused by mycobacteria, and a standard therapy remains to be established. For prosthetic vascular graft infections, it is ideal to provide surgical and medical treatment in parallel, but in this case, surgical treatment was difficult and, therefore, a conservative treatment was chosen. We attempted to increase the treatment success rate of this refractory disease by conducting a susceptibility test for mycobacteria and treating with different combinations of antimicrobial agents, which was ultimately effective. With our treatment approach, a good clinical course was obtained and continues at the present stage. Conclusion: Although prosthetic vascular graft infection resulting from mycobacteria is a refractory infectious disease, it may be curative to administer appropriate antibiotics based on the susceptibility test in addition to surgical treatment.

Keywords: prosthetic vascular graft infection, lung fistula, Mycobacterium fortuitum, conservative treatment

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Authors: Ilham Zaidi, P. Sankara Sarma, Quazi Taufique Ahmed, V. Raman Kutty, Khalid Umer Khayyam, Gurpreet Singh, Abhishek Royal

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Introduction: Tuberculosis is a global public health emergency, but it is particularly acute in India, which has the world's highest tuberculosis burden. Due to overpopulation, lack of sanitation, malnutrition, low living standards, and poor socioeconomic status, among other factors, it is India's most common infectious disease. The long period of treatment is one of the main reasons for considering it as a public health emergency. Consequently, there is an increase in patient noncompliance, which leads to treatment failure, adverse treatment outcomes, and deaths. This could lead to the growth of anti-TB drug resistance. According to the WHO, approximately 558 thousand new cases of Multi-Drug Resistance Tuberculosis were diagnosed worldwide, with 8.5 percent developed Extensively Drug Resistance Tuberculosis. Methodology: This study is a program-based cross-sectional descriptive survey of adult tuberculosis patients enrolled in the Delhi-based Revised National Tuberculosis Program. The study setting was 27 NTEP districts of Delhi. (N=65,893) and Sample size- was 200; the sampling method which is used in the study was the systemic random sampling method. Results: Most of the demographic factors (age, gender, residence, and family type) were not significantly associated with adherence; marital status was found statistically significant with the treatment compliance. Hesitation while telling people about the disease and motivation to strictly follow drug schedule by healthcare workers were other factors where a significant association with drug adherence was observed. The study findings also suggest that provision of food, minimal financial and other moral support from family, counseling, discussion and politeness by healthcare providers might also facilitate adherence. Discussion and Conclusions: For TB treatment, adherence, age, sex, socioeconomic status, types of accommodations, malnutrition, and personal hygiene should all be considered; similar results were observed in previous studies. In the care of TB patients, DOTS services, health workers, and family support play a significant role. According to the country's National Strategic Plan, the Indian government has set a goal of eliminating tuberculosis by 2025 and patients' compliance with TB care and treatment adherence is very crucial to achieve this aim. A cohort study will be able to give a better understanding of factors associated with adherence since this study may have missed some defaulters who were absconding and could not be reached. Important Terms: RNTCP, NTEP, DOTS, DS-TB, DR-TB, RR-TB, MDR-TB, XDR-TB, Treatment failure, Treatment relapse, Treatment adherence.

Keywords: treatment adherence, treatment relapse, treatment failure, drug resistance tuberculosis

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Authors: Yasmeen Jamal Alabdallat, Almutazballlah Bassam Qablan, Hamza Al-Salhi, Salameh Alarood, Ibraheem Alkhawaldeh, Obada Abunar, Adam Abdallah

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Obstructive sleep apnea (OSA) is a disorder caused by the repeated collapse of the upper airway during sleep. It is the most common cause of sleep-related breathing disorder, as OSA can cause loud snoring, daytime fatigue, or more severe problems such as high blood pressure, cardiovascular disease, coronary artery disease, insulin-resistant diabetes, and depression. The hypoglossal nerve stimulator (HNS) is an implantable medical device that reduces the occurrence of obstructive sleep apnea by electrically stimulating the hypoglossal nerve in rhythm with the patient's breathing, causing the tongue to move. This stimulation helps keep the patient's airways clear while they sleep. This systematic review and meta-analysis aimed to assess the clinical outcome of hypoglossal nerve stimulation as a treatment of obstructive sleep apnea. A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials was conducted from inception until August 2022. Studies assessing the following clinical outcomes (Apnea-Hypopnea Index (AHI), Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), Oxygen Desaturation Indices (ODI), (Oxygen Saturation (SaO2)) were pooled in the meta-analysis using Review Manager Software. We assessed the quality of studies according to the Cochrane risk-of-bias tool for randomized trials (RoB2), Risk of Bias In Non-randomized Studies - of Interventions (ROBINS-I), and a modified version of NOS for the non-comparative cohort studies.13 Studies (Six Clinical Trials and Seven prospective cohort studies) with a total of 817 patients were included in the meta-analysis. The results of AHI were reported in 11 studies examining OSA 696 patients. We found that there was a significant improvement in the AHI after 12 months of HNS (MD = 18.2 with 95% CI, (16.7 to 19.7; I2 = 0%); P < 0.00001). Further, 12 studies reported the results of ESS after 12 months of intervention with a significant improvement in the range of sleepiness among the examined 757 OSA patients (MD = 5.3 with 95% CI, (4.75 to 5.86; I2 = 65%); P < 0.0001). Moreover, nine studies involving 699 participants reported the results of FOSQ after 12 months of HNS with a significant reported improvement (MD = -3.09 with 95% CI, (-3.41 to 2.77; I2 = 0%); P < 0.00001). In addition, ten studies reported the results of ODI with a significant improvement after 12 months of HNS among the 817 examined patients (MD = 14.8 with 95% CI, (13.25 to 16.32; I2 = 0%); P < 000001). The Hypoglossal Nerve Stimulation showed a significant positive impact on obstructive sleep apnea patients after 12 months of therapy in terms of apnea-hypopnea index, oxygen desaturation indices, manifestations of the behavioral morbidity associated with obstructive sleep apnea, and functional status resulting from sleepiness.

Keywords: apnea, meta-analysis, hypoglossal, stimulation

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Authors: Elmira Davasaz Tabrizi, Mushteba Sevil, Ercan Arican

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Directly or indirectly, the human microbiome, or the population of bacteria and other microorganisms living in the human body, has been linked with human health. Various research has examined the connection with both illness status and the composition of the human microbiome, even though current studies indicate that the gut microbiome influences the mucosa and immune system. A significant amount of effort is being put into understanding the human microbiome's natural history in terms of health outcomes while also expanding our comprehension of the molecular connections between the microbiome and the host. To maintain health and avoid disease, these efforts ultimately seek to find efficient methods for recovering human microbial communities. This review article describes how the human microbiome leads to chronic diseases and discusses evidence for an important significant disorder that is related to the microbiome and linked to prostate cancer: chronic prostatitis (CP).

Keywords: urobiome, chronic prostatitis, metagenomic, urinary microbiome

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Authors: C. S. Chen, F. Y. Hui, B. S. Farhana, J. De Leon

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Introduction: Stroke can lead to long-term disability, affecting one’s quality of life. Providing stroke education to patient and family members is essential to optimize stroke recovery and prevent recurrent stroke. Currently, nurses conduct stroke education by handing out pamphlets and explaining their contents to patients. However, this is not always effective as nurses have varying levels of knowledge and depth of content discussed with the patient may not be consistent. With the advancement of information technology, health education is increasingly being disseminated via electronic software and studies have shown this to have benefitted patients. Hence, a multi-disciplinary team consisting of doctors, nurses and allied health professionals was formed to create the stroke journey map software to deliver consistent and concise stroke education. Research Objectives: To evaluate the effectiveness of using a stroke journey map software in improving patients’ perceived knowledge in the acute stroke unit during hospitalization. Methods: Patients admitted to the acute stroke unit were given stroke journey map software during patient education. The software consists of 31 interactive slides that are brightly coloured and 4 videos, based on input provided by the multi-disciplinary team. Participants were then assessed with pre-and-post survey questionnaires before and after viewing the software. The questionnaire consists of 10 questions with a 5-point Likert scale which sums up to a total score of 50. The inclusion criteria are patients diagnosed with ischemic stroke and are cognitively alert and oriented. This study was conducted between May 2017 to October 2017. Participation was voluntary. Results: A total of 33 participants participated in the study. The results demonstrated that the use of a stroke journey map as a stroke education medium was effective in improving patients’ perceived knowledge. A comparison of pre- and post-implementation data of stroke journey map revealed an overall mean increase in patients’ perceived knowledge from 24.06 to 40.06. The data is further broken down to evaluate patients’ perceived knowledge in 3 domains: (1) Understanding of disease process; (2) Management and treatment plans; (3) Post-discharge care. Each domain saw an increase in mean score from 10.7 to 16.2, 6.9 to 11.9 and 6.6 to 11.7 respectively. Project Impact: The implementation of stroke journey map has a positive impact in terms of (1) Increasing patient’s perceived knowledge which could contribute to greater empowerment of health; (2) Reducing need for stroke education material printouts making it environmentally friendly; (3) Decreasing time nurses spent on giving education resulting in more time to attend to patients’ needs. Conclusion: This study has demonstrated the benefit of using stroke journey map as a platform for stroke education. Overall, it has increased patients’ perceived knowledge in understanding their disease process, the management and treatment plans as well as the discharge process.

Keywords: acute stroke, education, ischemic stroke, knowledge, stroke

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Authors: Hossam N. Alhawatmeh, Areen I. Albustanji

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Hemodialysis negatively affects physical and psychological health. Pain, poor sleep quality, and low self-esteem are highly prevalent among patients with end-stage renal disease (ESRD) who receive hemodialysis, significantly increasing mortality and morbidity of those patients. Mind-body interventions (MBI), such as mindfulness meditation, have been recently gaining popularity that improved pain, sleep quality, and self-esteem in different populations. However, to our best knowledge, its effects on these health problems in patients receiving hemodialysis have not been studied in Jordan. Thus, the purpose of the study was to examine the effect of mindfulness meditation on pain, sleep quality, and self-esteem in patients with ESR receiving hemodialysis in Jordan. An experimental repeated-measures, randomized, parallel control design was conducted on (n =60) end-stage renal disease patients undergoing hemodialysis between March and June 2023 in the dialysis center at a public hospital in Jordan. Participants were randomly assigned to the experimental (n =30) and control groups (n =30) using a simple random assignment method. The experimental group practiced mindfulness meditation for 30 minutes three times per week for five weeks during their hemodialysis treatments. The control group's patients continued to receive hemodialysis treatment as usual for five weeks during hemodialysis sessions. The study variables for both groups were measured at baseline (Time 0), two weeks after intervention (Time 1), and at the end of intervention (Time 3). The numerical rating scale (NRS), the Rosenberg Self-Esteem Scale (RSES-M), and the Pittsburgh Sleep Quality Index (PSQI) were used to measure pain, self-esteem, and sleep quality, respectively. SPSS version 25 was used to analyze the study data. The sample was described by frequency, mean, and standard deviation as an appropriate. The repeated measures analysis of variance (ANOVA) tests were run to test the study hypotheses. The results of repeated measures ANOVA (within-subject) revealed that mindfulness meditation significantly decrease pain by the end of the intervention in the experimental group. Additionally, mindfulness meditation improved sleep quality and self-esteem in the experimental group, and these improvements occurred significantly after two weeks of the intervention and at the end of the intervention. The results of repeated measures ANOVA (within and between-subject) revealed that the experimental group, compared to the control group, experienced lower levels of pain and higher levels of sleep quality and self-esteem over time. In conclusion, the results provided substantial evidence supporting the positive impacts of mindfulness meditation on pain, sleep quality, and self-esteem in patients with ESRD undergoing hemodialysis. These results highlight the potential of mindfulness meditation as an adjunctive therapy in the comprehensive care of this patient population. Incorporating mindfulness meditation into the treatment plan for patients receiving hemodialysis may contribute to improved well-being and overall quality of life.

Keywords: hemodialysis, pain, sleep quality, self-esteem, mindfulness

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Authors: Mustafa M. Donma, Orkide Donma

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Obesity is associated with cardiovascular disease risk factors and metabolic syndrome (MetS). In this study, associations between adipokines and adipokine as well as obesity indices were evaluated. Plasma adipokine levels may exhibit variations according to body adipose tissue mass. Besides, upon consideration of obesity as an inflammatory disease, adipokines may play some roles in this process. The ratios of proinflammatory adipokines to adiponectin may act as highly sensitive indicators of body adipokine status. The aim of the study is to present some adipokine indices, which are thought to be helpful for the evaluation of childhood obesity and also to determine the best discriminators in the diagnosis of MetS. 80 prepubertal children (aged between 6-9.5 years) included in the study were divided into three groups; 30 children with normal weight (NW), 25 morbid obese (MO) children and 25 MO children with MetS. Physical examinations were performed. Written informed consent forms were obtained from the parents. The study protocol was approved by Ethics Committee of Namik Kemal University Medical Faculty. Anthropometric measurements, such as weight, height, waist circumference (C), hip C, head C, neck C were recorded. Values for body mass index (BMI), diagnostic obesity notation model assessment Index-II (D2 index) as well as waist-to-hip, head-to-neck ratios were calculated. Adiponectin, resistin, leptin, chemerin, vaspin, progranulin assays were performed by ELISA. Adipokine-to-adiponectin ratios were obtained. SPSS Version 20 was used for the evaluation of data. p values ≤ 0.05 were accepted as statistically significant. Values of BMI and D2 index, waist-to-hip, head-to-neck ratios did not differ between MO and MetS groups (p ≥ 0.05). Except progranulin (p ≤ 0.01), similar patterns were observed for plasma levels of each adipokine. There was not any difference in vaspin as well as resistin levels between NW and MO groups. Significantly increased leptin-to-adiponectin, chemerin-to-adiponectin and vaspin-to-adiponectin values were noted in MO in comparison with those of NW. The most valuable adipokine index was progranulin-to-adiponectin (p ≤ 0.01). This index was strongly correlated with vaspin-to-adiponectin ratio in all groups (p ≤ 0.05). There was no correlation between vaspin-to-adiponectin and chemerin-to--adiponectin in NW group. However, a correlation existed in MO group (r = 0.486; p ≤ 0.05). Much stronger correlation (r = 0.609; p ≤ 0.01) was observed in MetS group between these two adipokine indices. No correlations were detected between vaspin and progranulin as well as vaspin and chemerin levels. Correlation analyses showed a unique profile confined to MetS children. Adiponectin was found to be correlated with waist-to-hip (r = -0.435; p ≤ 0.05) as well as head-to-neck (r = 0.541; p ≤ 0.05) ratios only in MetS children. In this study, it has been investigated if adipokine indices have priority over adipokine levels. In conclusion, vaspin-to-adiponectin, progranulin-to-adiponectin, chemerin-to-adiponectin along with waist-to-hip and head-to-neck ratios were the optimal combinations. Adiponectin, waist-to-hip, head-to-neck, vaspin-to-adiponectin, chemerin-to-adiponectin ratios had appropriate discriminatory capability for MetS children.

Keywords: adipokine indices, metabolic syndrome, obesity indices, pediatric obesity

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Authors: Ng Liang Shen, Hau Yuan Wen

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Arrhythmia analysis of ECG signal plays a major role in diagnosing most of the cardiac diseases. Therefore, a single arrhythmia detection of an electrocardiographic (ECG) record can determine multiple pattern of various algorithms and match accordingly each ECG beats based on Machine Learning supervised learning. These researchers used different features and classification methods to classify different arrhythmia types. A major problem in these studies is the fact that the symptoms of the disease do not show all the time in the ECG record. Hence, a successful diagnosis might require the manual investigation of several hours of ECG records. The point of this paper presents investigations cardiovascular ailment in Electrocardiogram (ECG) Signals for Cardiac Arrhythmia utilizing examination of ECG irregular wave frames via heart beat as correspond arrhythmia which with Machine Learning Pattern Recognition.

Keywords: electrocardiogram, ECG, classification, machine learning, pattern recognition, detection, QRS

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Authors: Khalid Mohammed Idrees

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Endodontic treatment aims to reverse the disease process and thereby eliminate the associated signs of symptoms. When the treatment itself appears to initiate the onset of pain and /or swelling (endodontic flare-up), the result can be distressing to both the patient and the operator. Patient might even consider postoperative symptoms as a bench mark against which the clinician’s skills are measured. Obviously the treatment with the lowest prevalence of postoperative pain is usually the treatment of choice as long as effectiveness and cost are not compromised. Knowledge of the cause and mechanism behind intra appointment flare-up is of utmost importance for the clinician to properly prevent or manage this undesirable condition. This review lecture will discuss the causative factors of flare-up with special attention to the microorganism role, various modalities of preventive measures would be discussed. Those measures are based on scientific evidence combined with the long clinical experience of the lecturer.

Keywords: endodontic flare-up, causative factors, inflammatory mediators, preventive measures

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Authors: Chunxiao Wu, Dongyun Jiang, Tao Jiang, Luxia Xu, Qian Xu, Meng Zhao, Qin Zhu, Zhigang Guo, Jinlan Pan, Suning Chen

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The stability and evolution of human genetics depends on chromosomes (and chromosome-chromosome interactions). We wish to understand the spatial location of chromosomes in dividing cells in order to understand the relationship between chromosome-chromosome interactions and to further investigate the role of chromosomes and their impact on cell biological behavior. In this study, we explored the relative spatial positional relationships of chromosomes [t (9;22) and t (15;17)] in B-ALL cells by using the three-dimensions DNA in situ fluorescent hybridization (3D-FISH) method. The results showed that chromosomes [t (9;22) and t (15;17)] showed relatively stable spatial relationships. The relative stability of the spatial location of chromosomes in dividing cells may be relevant to disease.

Keywords: chromosome, human genetics, chromosome territory, 3D-FISH

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Authors: Retno Supriyanti, Ays Rahmadian Subhi, Yogi Ramadhani, Haris B. Widodo

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Alzheimer is one type of disease in the elderly that may occur in the world. The severity of the Alzheimer can be measured using a scale called Clinical Dementia Rating (CDR) based on a doctor's diagnosis of the patient's condition. Currently, diagnosis of Alzheimer often uses MRI machine, to know the condition of part of the brain called Hippocampus and Ventricle. MRI image itself consists of 3 slices, namely Coronal, Sagittal and Axial. In this paper, we discussed the measurement of the area of the ventricle especially in the Coronal slice based on the severity level referring to the CDR value. We use Active Contour method to segment the ventricle’s region, therefore that ventricle’s area can be calculated automatically. The results show that this method can be used for further development in the automatic diagnosis of Alzheimer.

Keywords: Alzheimer, CDR, coronal, ventricle, active contour

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Authors: Sukumar Namineni, Tracy O'Connor, Ulrich Kalinke, Percy Knolle, Mathias Heikenwaelder

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The liver is one of the pivotal organs in vertebrate animals, serving a multitude of functions such as metabolism, detoxification and protein synthesis and including a predominant role in innate immunity. The innate immune mechanisms pertaining to liver in controlling viral infections have largely been attributed to the Kupffer cells, the locally resident macrophages. However, all the cells of liver are equipped with innate immune functions including, in particular, the hepatocytes. Hence, our aim in this study was to elucidate the innate immune contribution of hepatocytes in viral clearance using mice lacking Ikkβ specifically in the hepatocytes, termed IkkβΔᴴᵉᵖ mice. Blockade of Ikkβ activation in IkkβΔᴴᵉᵖ mice affects the downstream signaling of canonical NF-κB signaling by preventing the nuclear translocation of NF-κB, an important step required for the initiation of innate immune responses. Interestingly, infection of IkkβΔᴴᵉᵖ mice with lymphocytic choriomeningitis virus (LCMV) led to strongly increased hepatic viral titers – mainly confined in clusters of infected hepatocytes. This was due to reduced interferon stimulated gene (ISG) expression during the onset of infection and a reduced CD8+ T-cell-mediated response. Decreased ISG production correlated with increased liver LCMV protein and LCMV in isolated hepatocytes from IkkβΔᴴᵉᵖ mice. A similar phenotype was found in LCMV-infected mice lacking interferon signaling in hepatocytes (IFNARΔᴴᵉᵖ) suggesting a link between NFkB and interferon signaling in hepatocytes. We also observed a failure of interferon-mediated inhibition of HBV replication in HepaRG cells treated with NF-kB inhibitors corroborating our initial findings with LCMV infections. Collectively, these results clearly highlight a previously unknown and influential role of hepatocytes in the induction of innate immune responses leading to viral clearance during a systemic viral infection with LCMV-WE.

Keywords: CD8+ T cell responses, innate immune mechanisms in the liver, interferon signaling, interferon stimulated genes, NF-kB signaling, viral clearance

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