Search results for: cohesive markers
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 915

Search results for: cohesive markers

255 Clinical Evaluation of Neutrophil to Lymphocytes Ratio and Platelets to Lymphocytes Ratio in Immune Thrombocytopenic Purpura

Authors: Aisha Arshad, Samina Naz Mukry, Tahir Shamsi

Abstract:

Background: Immune thrombocytopenia (ITP) is an autoimmune disorder. Besides platelets counts, immature platelets fraction (IPF) can be used as tool to predict megakaryocytic activity in ITP patients. The clinical biomarkers like Neutrophils to lymphocytes ratio (NLR) and platelet to lymphocytes ratio(PLR) predicts inflammation and can be used as prognostic markers.The present study was planned to assess the ratios in ITP and their utility in predicting prognosis after treatment. Methods: A total of 111 patients of ITP with same number of healthy individuals were included in this case control study during the period of January 2015 to December 2017.All the ITP patients were grouped according to guidelines of International working group of ITP. A 3cc blood was collected in EDTA tube and blood parameters were evaluated using Sysmex 1000 analyzer.The ratios were calculated by using absolute counts of Neutrophils,Lymphocytes and platelets.The significant (p=<0.05) difference between ITP patients and healthy control groups was determined by Kruskal wallis test, Dunn’s test and spearman’s correlation test was done using SPSS version 23. Results: The significantly raised total leucocytes counts (TLC) and IPF along with low platelets counts were observed in ITP patients as compared to healthy controls.In ITP groups,very low platelet count with median and IQR of 2(3.8)3x109/l with highest mean and IQR IPF 25.4(19.8)% was observed in newly diagnosed ITP group. The NLR was high with prognosis of disease as higher levels were observed in P-ITP. The PLR was significantly low in ND-ITP ,P-ITP, C-ITP, R-ITP and compared to controls with p=<0.001 as platelet were less in number in all ITP patients. Conclusion: The IPF can be used in evaluation of bone marrow response in ITP. The simple, reliable and calculated NLR and PLR ratios can be used in predicting prognosis and response to treatment in ITP and to some extend the severity of disease.

Keywords: neutrophils, platelets, lymphocytes, infection

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254 Analysis of Non-Coding Genome in Streptococcus pneumoniae for Molecular Epidemiology Typing

Authors: Martynova Alina, Lyubov Buzoleva

Abstract:

Streptococcus pneumoniae is the causative agent of pneumonias and meningitids throught all the world. Having high genetic diversity, this microorganism can cause different clinical forms of pneumococcal infections and microbiologically it is really difficult diagnosed by routine methods. Also, epidemiological surveillance requires more developed methods of molecular typing because the recent method of serotyping doesn't allow to distinguish invasive and non-invasive isolates properly. Non-coding genome of bacteria seems to be the interesting source for seeking of highly distinguishable markers to discriminate the subspecies of such a variable bacteria as Streptococcus pneumoniae. Technically, we proposed scheme of discrimination of S.pneumoniae strains with amplification of non-coding region (SP_1932) with the following restriction with 2 types of enzymes of Alu1 and Mn1. Aim: This research aimed to compare different methods of typing and their application for molecular epidemiology purposes. Methods: we analyzed population of 100 strains of S.pneumoniae isolated from different patients by different molecular epidemiology methods such as pulse-field gel electophoresis (PFGE), restriction polymorphism analysis (RFLP) and multilolocus sequence typing (MLST), and all of them were compared with classic typing method as serotyping. The discriminative power was estimated with Simpson Index (SI). Results: We revealed that the most discriminative typing method is RFLP (SI=0,97, there were distinguished 42 genotypes).PFGE was slightly less discriminative (SI=0,95, we identified 35 genotypes). MLST is still the best reference method (SI=1.0). Classic method of serotyping showed quite weak discriminative power (SI=0,93, 24 genotypes). In addition, sensivity of RFLP was 100%, specificity was 97,09%. Conclusion: the most appropriate method for routine epidemiology surveillance is RFLP with non-coding region of Streptococcsu pneumoniae, then PFGE, though in some cases these results should be obligatory confirmed by MLST.

Keywords: molecular epidemiology typing, non-coding genome, Streptococcus pneumoniae, MLST

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253 Biologically Synthesised Silver Nanoparticles Induces Autophagy and JNK Signaling as a Pro-Survival Response by Abrogating Reactive Oxygen Species Accumulation in Cancer Cells

Authors: Sudeshna Mukherjee, Leena Fageria, R. Venkataramana Dilip, Rajdeep Chowdhury, Jitendra Panwar

Abstract:

Metal nanoparticles in recent years have gained importance in cancer therapy due to their enhanced permeability retention effect. Among various nanomaterials, silver nanoparticles (AgNPs) have received considerable attention due to their unique properties like conductivity, chemical stability, relative lower toxicity and outstanding therapeutic potential, such as anti-inflammatory, antimicrobial and anti-cancerous activities. In this study, we took a greener approach to synthesize silver nanoparticle from fungus and analyze its effects on both epithelial and mesenchymal derived cancer cells. Much research has been done on nanoparticle-induced apoptosis, but little is known about its role in autophagy. In our study, the silver nanoparticles were seen to induce autophagy which was analyzed by studying the expression of several autophagy markers like, LC3B-II and ATG genes. Monodansylcadaverine (MDC) assay also revealed the induction of autophagy upon treatment with AgNPs. Inhibition of autophagy by chloroquine resulted in increased cell death suggesting autophagy as a survival strategy adopted by the cells. In parallel to autophagy induction, silver nanoparticles induced ROS accumulation. Interestingly, autophagy inhibition by chloroquine increased ROS level, resulting in enhanced cell death. We further analyzed MAPK signaling upon AgNP treatment. It was observed that along with autophagy, activation of JNK signaling served as pro-survival while ERK signaling served as a pro-death signal. Our results provide valuable insights into the role of autophagy upon AgNP exposure and provide cues to probabilistic strategies to effectively sensitize cancer cells.

Keywords: autophagy, JNK signalling, reactive oxygen species, silver nanoparticles

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252 Computational Homogenization of Thin Walled Structures: On the Influence of the Global vs Local Applied Plane Stress Condition

Authors: M. Beusink, E. W. C. Coenen

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The increased application of novel structural materials, such as high grade asphalt, concrete and laminated composites, has sparked the need for a better understanding of the often complex, non-linear mechanical behavior of such materials. The effective macroscopic mechanical response is generally dependent on the applied load path. Moreover, it is also significantly influenced by the microstructure of the material, e.g. embedded fibers, voids and/or grain morphology. At present, multiscale techniques are widely adopted to assess micro-macro interactions in a numerically efficient way. Computational homogenization techniques have been successfully applied over a wide range of engineering cases, e.g. cases involving first order and second order continua, thin shells and cohesive zone models. Most of these homogenization methods rely on Representative Volume Elements (RVE), which model the relevant microstructural details in a confined volume. Imposed through kinematical constraints or boundary conditions, a RVE can be subjected to a microscopic load sequence. This provides the RVE's effective stress-strain response, which can serve as constitutive input for macroscale analyses. Simultaneously, such a study of a RVE gives insight into fine scale phenomena such as microstructural damage and its evolution. It has been reported by several authors that the type of boundary conditions applied to the RVE affect the resulting homogenized stress-strain response. As a consequence, dedicated boundary conditions have been proposed to appropriately deal with this concern. For the specific case of a planar assumption for the analyzed structure, e.g. plane strain, axisymmetric or plane stress, this assumption needs to be addressed consistently in all considered scales. Although in many multiscale studies a planar condition has been employed, the related impact on the multiscale solution has not been explicitly investigated. This work therefore focuses on the influence of the planar assumption for multiscale modeling. In particular the plane stress case is highlighted, by proposing three different implementation strategies which are compatible with a first-order computational homogenization framework. The first method consists of applying classical plane stress theory at the microscale, whereas with the second method a generalized plane stress condition is assumed at the RVE level. For the third method, the plane stress condition is applied at the macroscale by requiring that the resulting macroscopic out-of-plane forces are equal to zero. These strategies are assessed through a numerical study of a thin walled structure and the resulting effective macroscale stress-strain response is compared. It is shown that there is a clear influence of the length scale at which the planar condition is applied.

Keywords: first-order computational homogenization, planar analysis, multiscale, microstrucutures

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251 Improving Infant Vaccination Rates Through Expanded Access to Care

Authors: Aidan Jacobsen, Morgan Motia, David Sam, Jonathan Mudge

Abstract:

Background: The Centers for Disease Control (CDC) lists vaccine requirements for children under two years old to correlate with development markers. CDC lists the coverage by age 24 months to be at least 90% nationally and 84% for Rhode Island Blackstone Valley Community Health Center (BVCHC) in Central Falls, Rhode Island, currently has a completed vaccination rate of 51% for children by the age of 24 months. Current barriers to care for up to date well child vaccinations include lack of transportation, parental work, childcare, and other social stressors. Objective: Increase the vaccination rate of children under the age of 24 months at BVCHC. Conduct a literature review to identify the common barriers preventing children under 24 months from receiving vaccinations. Reduce the barriers to expand access to vaccination care for infants Methods: Setting: Blackstone Valley Community Health Center, Pawtucket, RI Participants: (n=41), Patients between the age of 20-24 months, not up to date with the CDC vaccination recommendations and without a future appointment. QI Intervention: Patients were contacted via phone and offered an appointment during extra Saturday clinic hours in order to receive up to date vaccine care. A Saturday vaccine clinic was established specifically for patients in need of vaccines and having identified barriers to care. Conclusions: Expanding clinic hours and targeting non vaccine up –to-date patients can increase the current standard of childhood immunizations at BVCHC. Overcoming barriers preventing childhood immunization can improve access to providing up to date vaccinations. Other barriers still deter from reaching the national standard of immunizations rates.

Keywords: vaccinations, well child care, barriers to care, social determinants of health

Procedia PDF Downloads 55
250 Solid Phase Micro-Extraction/Gas Chromatography-Mass Spectrometry Study of Volatile Compounds from Strawberry Tree and Autumn Heather Honeys

Authors: Marinos Xagoraris, Elisavet Lazarou, Eleftherios Alissandrakis, Christos S. Pappas, Petros A. Tarantilis

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Strawberry tree (Arbutus unedo L.) and autumn heather (Erica manipuliflora Salisb.) are important beekeeping plants of Greece. Six monofloral honeys (four strawberry tree, two autumn heather) were analyzed by means of Solid Phase Micro-Extraction (SPME, 60 min, 60 oC) followed by Gas Chromatography coupled to Mass Spectrometry (GC-MS) for the purpose of assessing the botanical origin. A Divinylbenzene/Carboxen/Polydimethylsiloxane (DVB/CAR/PDMS) fiber was employed, and benzophenone was used as internal standard. The volatile compounds with higher concentration (μg/ g of honey expressed as benzophenone) from strawberry tree honey samples, were α-isophorone (2.50-8.12); 3,4,5-trimethyl-phenol (0.20-4.62); 2-hydroxy-isophorone (0.06-0.53); 4-oxoisophorone (0.38-0.46); and β-isophorone (0.02-0.43). Regarding heather honey samples, the most abundant compounds were 1-methoxy-4-propyl-benzene (1.22-1.40); p-anisaldehyde (0.97-1.28); p-anisic acid (0.35-0.58); 2-furaldehyde (0.52-0.57); and benzaldehyde (0.41-0.56). Norisoprenoids are potent floral markers for strawberry-tree honey. β-isophorone is found exclusively in the volatile fraction of this type of honey, while also α-isophorone, 4-oxoisophorone and 2-hydroxy-isophorone could be considered as additional marker compounds. The analysis of autumn heather honey revealed that phenolic compounds are the most abundant and p-anisaldehyde; 1-methoxy-4-propyl-benzene; and p-anisic acid could serve as potent marker compounds. In conclusion, marker compounds for the determination of the botanical origin for these honeys could be identified as several norisoprenoids and phenolic components were found exclusively or in higher concentrations compared to common Greek honey varieties.

Keywords: SPME/GC-MS, volatile compounds, heather honey, strawberry tree honey

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249 Human-Machine Cooperation in Facial Comparison Based on Likelihood Scores

Authors: Lanchi Xie, Zhihui Li, Zhigang Li, Guiqiang Wang, Lei Xu, Yuwen Yan

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Image-based facial features can be classified into category recognition features and individual recognition features. Current automated face recognition systems extract a specific feature vector of different dimensions from a facial image according to their pre-trained neural network. However, to improve the efficiency of parameter calculation, an algorithm generally reduces the image details by pooling. The operation will overlook the details concerned much by forensic experts. In our experiment, we adopted a variety of face recognition algorithms based on deep learning, compared a large number of naturally collected face images with the known data of the same person's frontal ID photos. Downscaling and manual handling were performed on the testing images. The results supported that the facial recognition algorithms based on deep learning detected structural and morphological information and rarely focused on specific markers such as stains and moles. Overall performance, distribution of genuine scores and impostor scores, and likelihood ratios were tested to evaluate the accuracy of biometric systems and forensic experts. Experiments showed that the biometric systems were skilled in distinguishing category features, and forensic experts were better at discovering the individual features of human faces. In the proposed approach, a fusion was performed at the score level. At the specified false accept rate, the framework achieved a lower false reject rate. This paper contributes to improving the interpretability of the objective method of facial comparison and provides a novel method for human-machine collaboration in this field.

Keywords: likelihood ratio, automated facial recognition, facial comparison, biometrics

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248 Determining Cellular Biomarkers Sensitive to Low Damaging Exposure

Authors: Svetlana Guryeva, Inna Kornienko, Elena Petersen

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At present, translational medicine is a rapidly developing branch of biomedicine. The main idea of translational medicine is a practical application of fundamental research. One of the possible applications for translational medicine is researching therapies that improve human age-related organism condition. To fill the gap between experiments and clinical practice, it is necessary to create the standardized system for the investigation of different effects on cellular aging models. In this study, primary human fibroblasts derived from patients of different ages were used as a cellular aging model. The senescence-associated β-galactosidase activity, lipofuscin, γ-H2AX, the reactive oxygen species level, and cell death markers (annexin V/propidium iodide) were used as biomarkers of the cell functional state. The effects of damaging exposures (oxidative stress and heat shock), potential positive factors (metformin and acetaminophen), and their combinations were investigated using the described biomarkers. Oxidative stress and heat shock caused the increase in the levels of all biomarkers, and only the cells from young patients partly coped with stress 3 days after the exposures. Metformin improved the state of pretreatment cells from young and old patients. The acetaminophen did not show significant changes in the biomarker levels compare to the action of metformin. This study proved the opportunity to develop a standardized screening system based on biomarkers of the cell functional state to identify potential positive or negative effects of some physical and chemical exposures. Moreover, such a system can be useful for the aims of regenerative medicine to determine the effect of cell pretreatment before transplantation.

Keywords: biomarkers, primary fibroblasts, regenerative medicine, senescence, test system, translational medicine

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247 In silico Analysis towards Identification of Host-Microbe Interactions for Inflammatory Bowel Disease Linked to Reactive Arthritis

Authors: Anukriti Verma, Bhawna Rathi, Shivani Sharda

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Reactive Arthritis (ReA) is a disorder that causes inflammation in joints due to certain infections at distant sites in the body. ReA begins with stiffness, pain, and inflammation in these areas especially the ankles, knees, and hips. It gradually causes several complications such as conjunctivitis in the eyes, skin lesions in hand, feet and nails and ulcers in the mouth. Nowadays the diagnosis of ReA is based upon a differential diagnosis pattern. The parameters for differentiating ReA from other similar disorders include physical examination, history of the patient and a high index of suspicion. There are no standard lab tests or markers available for ReA hence the early diagnosis of ReA becomes difficult and the chronicity of disease increases with time. It is reported that enteric disorders such as Inflammatory Bowel Disease (IBD) that is inflammation in gastrointestinal tract namely Crohn’s Disease (CD) and Ulcerative Colitis (UC) are reported to be linked with ReA. Several microorganisms are found such as Campylobacter, Salmonella, Shigella and Yersinia causing IBD leading to ReA. The aim of our study was to perform the in-silico analysis in order to find interactions between microorganisms and human host causing IBD leading to ReA. A systems biology approach for metabolic network reconstruction and simulation was used to find the essential genes of the reported microorganisms. Interactomics study was used to find the interactions between the pathogen genes and human host. Genes such as nhaA (pathogen), dpyD (human), nagK (human) and kynU (human) were obtained that were analysed further using the functional, pathway and network analysis. These genes can be used as putative drug targets and biomarkers in future for early diagnosis, prevention, and treatment of IBD leading to ReA.

Keywords: drug targets, inflammatory bowel disease, reactive arthritis, systems biology

Procedia PDF Downloads 252
246 White Wine Discrimination Based on Deconvoluted Surface Enhanced Raman Spectroscopy Signals

Authors: Dana Alina Magdas, Nicoleta Simona Vedeanu, Ioana Feher, Rares Stiufiuc

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Food and beverages authentication using rapid and non-expensive analytical tools represents nowadays an important challenge. In this regard, the potential of vibrational techniques in food authentication has gained an increased attention during the last years. For wines discrimination, Raman spectroscopy appears more feasible to be used as compared with IR (infrared) spectroscopy, because of the relatively weak water bending mode in the vibrational spectroscopy fingerprint range. Despite this, the use of Raman technique in wine discrimination is in an early stage. Taking this into consideration, the wine discrimination potential of surface-enhanced Raman scattering (SERS) technique is reported in the present work. The novelty of this study, compared with the previously reported studies, concerning the application of vibrational techniques in wine discrimination consists in the fact that the present work presents the wines differentiation based on the individual signals obtained from deconvoluted spectra. In order to achieve wines classification with respect to variety, geographical origin and vintage, the peaks intensities obtained after spectra deconvolution were compared using supervised chemometric methods like Linear Discriminant Analysis (LDA). For this purpose, a set of 20 white Romanian wines from different viticultural Romanian regions four varieties, was considered. Chemometric methods applied directly to row SERS experimental spectra proved their efficiency, but discrimination markers identification found to be very difficult due to the overlapped signals as well as for the band shifts. By using this approach, a better general view related to the differences that appear among the wines in terms of compositional differentiation could be reached.

Keywords: chemometry, SERS, variety, wines discrimination

Procedia PDF Downloads 135
245 Oxidative and Hormonal Disruptions Underlie Bisphenol A: Induced Testicular Toxicity in Male Rabbits

Authors: Kadry M. Sadek, Tarek K. Abouzed, Mousa A. Ayoub

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The presence of endocrine-disrupting compounds, such as bisphenol A (BPA), in the environment can cause serious health problems. However, there are controversial opinions. This study investigated the reproductive, metabolic, oxidative and immunologic-disrupting effects of bisphenol A in male rabbits. Rabbits were divided into five groups. The first four rabbit groups were administered oral BPA (1, 10, 50, or 100 mg/kg/day) for ten weeks. The fifth group was administered corn oil as the vehicle. BPA significantly decreased serum testosterone, estradiol and the free androgen index (FAI) and significantly increased sex hormone binding globulin (SHBG) compared with the placebo group. The higher doses of BPA showed a significant decrease in follicular stimulating hormone (FSH) and luteinizing hormone (LH). A significant increase in blood glucose levels was identified in the BPA groups. The non-significant difference in insulin levels is a novel finding. The cumulative testicular toxicity of BPA was clearly demonstrated by the dose-dependent decrease in absolute testes weight, primary measures of semen quality and a significant increase in testicular malonaldehyde (MDA). Moreover, BPA significantly decreased total antioxidant capacity (TAC) and significantly increased immunoglobulin G (IgG) at the highest concentration. Our results suggest that BPA, especially at higher doses, is associated with many adverse effects on metabolism, oxidative stress, immunity, sperm quality and markers of androgenic action. These results may reflect the estrogenic effects of BPA, which we hypothesize could be related, in part, to an inhibitory effect on testicular steroidogenesis. The induction of oxidative stress by BPA may play an additional role in testicular toxicity. These results suggest that BPA poses a threat to endocrine and reproductive functions.

Keywords: bisphenol A, oxidative stress, rabbits, semen quality, steroidogenesis

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244 Research on the Role of Platelet Derived Growth Factor Receptor Beta in Promoting Dedifferentiation and Pulmonary Metastasis of Osteosarcoma Under Hypoxic Microenvironment

Authors: Enjie Xu, Zhen Huang, Kunpeng Zhu, Jianping Hu, Xiaolong Ma, Yongjie Wang, Jiazhuang Zhu, Chunlin Zhang

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Abstract: Hypoxia and dedifferentiation of osteosarcoma (OS) cells leads to poor prognosis. We plan to identify the role of hypoxia on dedifferentiation and the associated signaling pathways. We performed a sphere formation assay and determined spheroid cells as dedifferentiated cells by detecting stem cell-like markers. RNAi assay was used to explore the expression relationship between hypoxia inducible factor 1 subunit alpha (HIF1A) and platelet derived growth factor receptor beta (PDGFRB). We obtained PDGFRB knockdown and overexpression cells through lentiviral infection experiments and the effects of PDGFRB on cytoskeleton rearrangement and cell adhesion were explored by immunocytochemistry. Wound-healing experiments, transwell assays, and animal trials were employed to investigate the effect of PDGFRB on OS metastasis. Dedifferentiated OS cells were found to exhibit high expression of HIF1A and PDGFRB, and HIF1A promoted the expression of PDGFRB, subsequently activated ras homolog family member A (RhoA), and increased the phosphorylation of myosin light chain (MLC). PDGFRB also enhanced the phosphorylation of focal adhesion kinase (FAK). The OS cell morphology and vinculin distribution were altered by PDGFRB. PDGFRB also promoted cell dedifferentiation and had a significant impact on the metastasis of OS cells both in vitro and in vivo. Our results demonstrated that HIF1A up-regulated PDGFRB under hypoxic conditions, and PDGFRB regulated the actin cytoskeleton by activating RhoA and subsequently phosphorylating MLC, thereby promoting OS dedifferentiation and pulmonary metastasis.

Keywords: osteosarcoma, dedifferentiation, metastasis, cytoskeleton rearrangement, PDGFRB, hypoxia

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243 Spironolactone in Psoriatic Arthritis: Safety, Efficacy and Effect on Disease Activity

Authors: Ashit Syngle, Inderjit Verma, Pawan Krishan

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Therapeutic approaches used previously relied on disease-modifying antirheumatic drugs (DMARDs) that had only partial clinical benefit and were associated with significant toxicity. Spironolactone, an oral aldosterone antagonist, suppresses inflammatory mediators. Clinical efficacy of spironolactone compared with placebo in patients with active psoriatic arthritis despite treatment with prior traditional DMARDs. In the 24-week, placebo-controlled study patients (n=31) were randomized to placebo and spironolactone (2 m/kg/day). Patients on background concurrent DMARDs continued stable doses (methotrexate, leflunomide, and/or sulfasalazine). Primary outcome measures were the assessment of disease activity measures i.e. 28-joint disease activity score (DAS28) and diseases activity in psoriatic arthritis (DAPSA) at week 24. The key secondary endpoint was change from baseline in Health Assessment Questionnaire–Disability Index (HAQ-DI) at week 24. Additional efficacy outcome measures at week 24 included improvements in the markers of inflammation (ESR and CRP) and pro-inflammatory cytokines TNF-α, IL-6 and IL-1. At week 24, spironolactone significantly reduced disease activity measure DAS-28 (p<0.001) and DAPSA (p=0.001) compared with placebo. Significant improvements in key secondary measures HAQ-DI (disability index) were evident with spironolactone (p=0.02) versus placebo. After week 24, there was significant reduction in pro-inflammatory cytokines level TNF-α, IL-6 (p<0.01) as compared with placebo group. However, there was no significant improvement in IL-1 in both treatment and placebo groups. There were minor side effects which did not mandate stopping of spironolactone. No change in any biochemical profile was noted after spironolactone treatment. Spironolactone was effective in the treatment of PsA, improving disease activity, physical function and suppressing the level of pro-inflammatory cytokines. Spironolactone demonstrated an acceptable safety profile and was well tolerated.

Keywords: spironolactone, inflammation, inflammatory cytokine, psoriatic arthritis

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242 Protective Effect of Vitamin D on Cardiac Apoptosis in Obese Rats

Authors: Kadeejah Alsolami, Zainab Alrefay, Husaam Awad

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Obesity and vitamin D deficiency have both been related to cardiovascular disease. The present work aimed to investigate the possible protective effect of vitamin D on cardiac apoptosis in a rat model of dietary-induced obesity. Methods: 30 male Wistar rats included in this study. They were allocated into 4 groups: Control (n=5), animal were fed standard diet for 3 months: Control + vitamin D (VD) (n=5),animals were fed a standard diet with 400IU VD/kg for 3 months: hypercaloric diets group (n=10), animals were fed a high fat diet for 3 months: hypercaloric diet with VD group (n=10), animals were fed a high fat diet with 400IU VD/kg for 3 months. At the beginning of the experiment, the weight and length were measured to assess body mass index (BMI) and repeated every 45 days. Food intake and body weight were monitored throughout the study period. Then rats were sacrificed and heart tissues collected for Quantitative Real-time polymerase chain reaction (qRT-PCR). qRT-PCR used to detect different genetic markers of apoptosis (anti-apoptotic gene (BCL2), a pro-apoptotic gene(BAX), pro-apoptotic genes (FAS, FAS-L), tumour necrosis factor (TNF), mitogen-activated protein kinases (MAPK). Results: FAS and FAS-L gene expression were significantly upregulated in rats fed with high fat diet. And FAS-L gene expression was significantly upregulated in all groups on comparison with control. Whereas Bax gene expression was significantly downregulated in rats fed with high-fat diet supplied with vitamin D. TNF was significantly upregulated in rats fed with high-fat diet treated with vitamin D. MAPK was significantly upregulated in rats fed with high fat diet group, and in rats fed with high-fat diet supplied with vitamin D. Conclusion: The cardiac apoptotic pathways were more activated in rats fed with high-fat than lean rats. And vitamin D protect the heart from the cardiac mitochondrial-dependent apoptotic pathway.

Keywords: apoptosis, heart, obesity, Vitamin D

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241 Utility of CK7, CK20 and CDX-2 as a Potential Panel in Differentiating Primary Ovarian Surface Epithelial Tumors from Metastatic Adenocarcinoma to the Ovary

Authors: Ghada Esheba, Ghadeer Aldoobi, Salwa Almalk, Abrar Alshareef, Eman Al-khairi, Eman Yaseen

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Background: In Saudi Arabia, ovarian cancer ranked seventh among female population and is the most common female genital tract malignancy after endometrial cancer. A slight increase in the incidence of ovarian cancer was observed from 2001–2008. Makkah, Riyadh, and the eastern region of Saudi Arabia had the highest incidence rate ratio for the number of ovarian cancer cases (1). Differentiating metastatic adenocarcinomas from primary ovarian carcinomas, especially those of endometrioid and mucinous type is clinically significant and a challenge for clinicians and pathologists, yet the distinction has important therapeutic and prognostic implications. Aim: To clarify the most important histopathological criteria to differentiate between primary ovarian surface epithelial tumors especially mucinous and endometrioid subtypes, and metastatic adenocarcinoma and to evaluate the value of a panel of antibodies consisting of CK7, CK20, and CDX-2 in the distinction between primary ovarian surface epithelial tumors and metastatic adenocarcinoma. Material and methods: This study was carried out on 26 cases of primary ovarian surface epithelial neoplasms and 14 cases of metastatic ovarian adenocarcinoma. All cases were studied immunohistochemically using CK7, CK20, and CDX-2. Results: All cases of primary ovarian adenocarcinoma were positive for CK7. 25% and 58% of mucinous borderline mucinous tumor and mucinous carcinoma respectively were positive for CK20. Only 42% of mucinous carcinoma were positive for CDX-2. All cases of endometrioid carcinomas were negative for both CK20 and CDX-2. All cases of metastatic adenocarcinoma from the colon were negative for CK7 and positive for CK20 and CDX-2. Conclusions: CK7 is an important positive marker for primary ovarian tumors, while CK20 and CDX-2 are useful markers for colorectal carcinoma metastatic to the ovary. Caution should be taken as primary ovarian mucinous tumors may stain positive for CK20, CDX-2, or both, however, they usually exhibit a focal pattern of reactivity.

Keywords: adenoma, endometrioid, malignancy, ovarian

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240 Association of ApoB, CETP and GALNT2 Genetic Variants with Type 2 Diabetes-Related Traits in Population from Bosnia and Herzegovina

Authors: Anida Causevic-Ramosevac, Sabina Semiz

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The aim of this study was to investigate the association of four single nucleotide polymorphisms (SNPs) - rs673548, rs693 in ApoB gene, rs1800775 in CETP gene and rs4846914 in GALNT2 gene with parameters of type 2 diabetes (T2D) and diabetic dyslipidemia in the population of Bosnia and Herzegovina (BH). Materials and methods: Our study involved 352 patients with T2D and 156 healthy subjects. Biochemical and anthropometric parameters were measured in all participants. DNA was extracted from the peripheral blood for the purpose of genetic testing. Polymorphisms in ApoB (rs673548, rs693), CETP (rs1800775) and GALNT2 (rs4846914) genes were analyzed by using Sequenom IPLEX platform. Results: Our results demonstrated significant associations for rs180075 polymorphism in CETP gene with levels of fasting insulin (p = 0.020; p = 0.027; p = 0.044), triglycerides (p = 0.046) and ALT (p = 0.031) activity in control group. In group of diabetic patients, results showed a significant association of rs673548 in ApoB gene with levels of fasting insulin (p = 0.008), HOMA-IR (p = 0.013), VLDL-C (p = 0.037) and CRP (p = 0.029) and rs693 in ApoB gene with BMI (p = 0.025), systolic blood pressure (p = 0.027), fasting insulin (p = 0.037) and HOMA-IR (p = 0.023) levels. Significant associations were also observed for rs1800775 in CETP gene with triglyceride (p = 0.023) levels and rs4846914 in GALNT2 gene with HbA1C (p = 0.013) and triglyceride (p = 0.043) levels. Conclusion: In conclusion, this is the first study that examined the impact of variations of candidate genes on a wide range of metabolic parameters in BH population. Our results suggest an association of variations of ApoB, CETP and GALNT2 genes with specific markers of T2D and dyslipidemia. Further studies would be needed in order to confirm these genetic effects in other ethnic groups as well.

Keywords: ApoB, CETP, dyslipidemia, GALNT2, type 2 diabetes

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239 Effect of Doping on Band Gap of Zinc Oxide and Degradation of Methylene Blue and Industrial Effluent

Authors: V. P. Borker, K. S. Rane, A. J. Bhobe, R. S. Karmali

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Effluent of dye industries contains chemicals and organic dyes. Sometimes they are thrown in the water bodies without any treatment. This leads to environmental pollution and is detrimental to flora and fauna. Semiconducting oxide zinc oxide with wide bandgap 3.37 eV is used as a photocatalyst in degrading organic dyes using UV radiations. It generates electron-hole pair on exposure to UV light. If degradation is aimed at solar radiations, bandgap of zinc oxide is to be reduced so as to utilize visible radiation. Thus, in present study, zinc oxide, ZnO is synthesized from zinc oxalate, N doped zinc oxide, ZnO₁₋ₓNₓ from hydrazinated zinc oxalate, cadmium doped zinc oxide Zn₀.₉Cd₀.₁₀ and magnesium-doped zinc oxide Zn₀.₉Mg₀.₁₀ from mixed metal oxalate and hydrazinated mixed metal oxalate. The precursors were characterized by FTIR. They were decomposed to form oxides and XRD were recorded. The compounds were monophasic. Bandgap was calculated using Diffuse Reflectance Spectrum. The bandgap of ZnO was reduced to 3.24 because of precursor method of synthesis leading large surface area. The bandgap of Zn₀.₉Cd₀.₁₀ was 3.11 eV and that of Zn₀.₉Mg₀.₁₀ 3.41 eV. The lowest value was of ZnO₁₋ₓNₓ 3.09 eV. These oxides were used to degrade methylene blue, a model dye in sunlight. ZnO₁₋ₓNₓ was also used to degrade effluent of industry manufacturing colours, crayons and markers. It was observed that ZnO₁₋ₓNₓ acts as a good photocatalyst for degradation of methylene blue. It can degrade the solution within 120 minutes. Similarly, diluted effluent was decolourised using this oxide. Some colours were degraded using ZnO. Thus, the use of these two oxides could mineralize effluent. Lesser bandgap leads to more electro hole pair thus helps in the formation of hydroxyl ion radicals. These radicals attack the dye molecule, fragmentation takes place and it is mineralised.

Keywords: cadmium doped zinc oxide, dye degradation, dye effluent degradation, N doped zinc oxide, zinc oxide

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238 Teacher Knowledge: Unbridling Teacher Agency in the Context of Professional Development for Transformative Teaching and Learning

Authors: Bernice Badal

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This article addresses a persistent challenge related to teacher agency in knowledge acquisition in professional development (PD) workshops in contexts of educational change, given that scholarship identifies a need for more teacher involvement and amplification of teacher's voices. Theoretical concepts are drawn from Bandura’s Social cognitive theory, incorporating the triadic causation model of agency to examine the reciprocal nature of the context, teacher characteristics, and systemic influences that shape how knowledge is transmitted and acquired in PD workshops. This qualitative study, using a mix of classroom observations and interviews, explored the political, contextual, and personal characteristics of teacher agency in PD through an analysis of data extracted from a PhD study. The narratives of six teachers from three township schools are examined to show how PD efforts in South Africa have failed to take account of the holistic development of teacher agency in knowledge dissemination and how this shapes teacher self-efficacy beliefs about being able to masterfully apply the tenets of the reform. Agency, teacher voice, and contextual considerations were used as markers of the quality of the training provided to understand how knowledge is acquired and meaning is made. The findings suggest that systemic influences of institutionally imposed PD offer partial understandings of the reform, which is offered in traditional formats that do not consider teacher empowerment in knowledge production and the development of teacher agency. Common in all the participants’ responses is the need for more information and training on the prescribed approach for teaching English as a second language; however, this paper holds the view that more information may not solve teachers’ dilemmas. Accordingly, it recommends a restructuring of the programme with facilitators being more cognisant of teacher agency for the development of transformative teachers. The findings of the study contribute to the field of teacher knowledge, teacher training, and professional development in the context of educational reforms.

Keywords: teacher professional development, teacher voice, teacher agency, educational reforms, teacher knowledge

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237 Gene Distribution of CB1 Receptor rs2023239 in Thailand Cannabis Patients

Authors: Tanyaporn Chairoch

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Introduction: Cannabis is a drug to treat patients with many diseases such as Multiple sclerosis, Alzheimer’s disease, and Epilepsy, where theycontain many active compounds such as delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD). Especially, THC is the primary psychoactive ingredient in cannabis and binds to cannabinoid 1 (CB1) receptors. Moreover, CB1 is located on the neocortex, hippocampus, basal ganglia, cerebellum, and brainstem. In previous study, we found the association between the variant of CB1recptors gene (rs2023239) and decreased effect of nicotine reinforcement in patients. However, there are no data describing whether the distribution of CB1 receptor gene is a genetic marker for Thai patients who are treated with cannabis. Objective: Thus, the aim of this study we want to investigate the frequency of the CB1 receptor gene in Thai patients. Materials and Methods: All of sixty Thai patients received the medical cannabis for treatment who were recruited in this study. DNA will be extracted from EDTA whole blood by Genomic DNA Mini Kit. The genotyping of CNR1 gene (rs 2023239) was genotyped by the TaqMan real time PCR assay (ABI, Foster City, CA, USA).and using the real-time PCR ViiA7 (ABI, Foster City, CA, USA). Results: We found thirty-eight (63.3%) Thai patients were female, and twenty-two (36.70%) were male in this study with median age of 45.8 (range19 – 87 ) years. Especially, thirty-two (53.30%) medical cannabis tolerant controls were female ( 55%) and median age of52.1 (range 27 – 79 ) years. The most adverse effects for medical cannabis treatment was tachycardia. Furthermore, the number of rs 2023239 (TT) carriers was 26 of 27 (96.29%) in medical cannabis-induced adverse effects and 32 of 33 (96.96%) in tolerant controls. Additionally, rs 2023239 (CT) variant was found just only one of twenty-seven (3.7%) in medical cannabis-induced adverse effects and 1 of 33 (3.03%) in tolerant controls. Conclusions: The distribution of genetic variant in CNR1 gene might serve as a pharmacogenetics markers for screening before initiating the therapy with medical cannabis in Thai patients.

Keywords: cannabis, pharmacogenetics, CNR1 gene, thai patient

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236 Characterization and Correlation of Neurodegeneration and Biological Markers of Model Mice with Traumatic Brain Injury and Alzheimer's Disease

Authors: J. DeBoard, R. Dietrich, J. Hughes, K. Yurko, G. Harms

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Alzheimer’s disease (AD) is a predominant type of dementia and is likely a major cause of neural network impairment. The pathogenesis of this neurodegenerative disorder has yet to be fully elucidated. There are currently no known cures for the disease, and the best hope is to be able to detect it early enough to impede its progress. Beyond age and genetics, another prevalent risk factor for AD might be traumatic brain injury (TBI), which has similar neurodegenerative hallmarks. Our research focuses on obtaining information and methods to be able to predict when neurodegenerative effects might occur at a clinical level by observation of events at a cellular and molecular level in model mice. First, we wish to introduce our evidence that brain damage can be observed via brain imaging prior to the noticeable loss of neuromuscular control in model mice of AD. We then show our evidence that some blood biomarkers might be able to be early predictors of AD in the same model mice. Thus, we were interested to see if we might be able to predict which mice might show long-term neurodegenerative effects due to differing degrees of TBI and what level of TBI causes further damage and earlier death to the AD model mice. Upon application of TBIs via an apparatus to effectively induce extremely mild to mild TBIs, wild-type (WT) mice and AD mouse models were tested for cognition, neuromuscular control, olfactory ability, blood biomarkers, and brain imaging. Experiments are currently still in process, and more results are therefore forthcoming. Preliminary data suggest that neuromotor control diminishes as well as olfactory function for both AD and WT mice after the administration of five consecutive mild TBIs. Also, seizure activity increases significantly for both AD and WT after the administration of the five TBI treatment. If future data supports these findings, important implications about the effect of TBI on those at risk for AD might be possible.

Keywords: Alzheimer's disease, blood biomarker, neurodegeneration, neuromuscular control, olfaction, traumatic brain injury

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235 Linguistic Misinterpretation and the Dialogue of Civilizations

Authors: Oleg Redkin, Olga Bernikova

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Globalization and migrations have made cross-cultural contacts more frequent and intensive. Sometimes, these contacts may lead to misunderstanding between partners of communication and misinterpretations of the verbal messages that some researchers tend to consider as the 'clash of civilizations'. In most cases, reasons for that may be found in cultural and linguistic differences and hence misinterpretations of intentions and behavior. The current research examines factors of verbal and non-verbal communication that should be taken into consideration in verbal and non-verbal contacts. Language is one of the most important manifestations of the cultural code, and it is often considered as one of the special features of a civilization. The Arabic language, in particular, is commonly associated with Islam and the language and the Arab-Muslim civilization. It is one of the most important markers of self-identification for more than 200 million of native speakers. Arabic is the language of the Quran and hence the symbol of religious affiliation for more than one billion Muslims around the globe. Adequate interpretation of Arabic texts requires profound knowledge of its grammar, semantics of its vocabulary. Communicating sides who belong to different cultural groups are guided by different models of behavior and hierarchy of values, besides that the vocabulary each of them uses in the dialogue may convey different semantic realities and vary in connotations. In this context direct, literal translation in most cases cannot adequately convey the original meaning of the original message. Besides that peculiarities and diversities of the extralinguistic information, such as the body language, communicative etiquette, cultural background and religious affiliations may make the dialogue even more difficult. It is very likely that the so called 'clash of civilizations' in most cases is due to misinterpretation of counterpart's means of discourse such as language, cultural codes, and models of behavior rather than lies in basic contradictions between partners of communication. In the process of communication, one has to rely on universal values rather than focus on cultural or religious peculiarities, to take into account current linguistic and extralinguistic context.

Keywords: Arabic, civilization, discourse, language, linguistic

Procedia PDF Downloads 197
234 Angiogenic and Immunomodulatory Properties and Phenotype of Mesenchymal Stromal Cells Can Be Regulated by Cytokine Treatment

Authors: Ekaterina Zubkova, Irina Beloglazova, Iurii Stafeev, Konsyantin Dergilev, Yelena Parfyonova, Mikhail Menshikov

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Mesenchymal stromal cells from adipose tissue (MSC) currently are widely used in regenerative medicine to restore the function of damaged tissues, but that is significantly hampered by their heterogeneity. One of the modern approaches to overcoming this obstacle is the polarization of cell subpopulations into a specific phenotype under the influence of cytokines and other factors that activate receptors and signal transmission to cells. We polarized MSC with factors affecting the inflammatory signaling and functional properties of cells, followed by verification of their expression profile and ability to affect the polarization of macrophages. RT-PCR evaluation showed that cells treated with LPS, interleukin-17, tumor necrosis factor α (TNF α), primarily express pro-inflammatory factors and cytokines, and after treatment with polyninosin polycytidic acid and interleukin-4 (IL4) anti-inflammatory factors and some proinflammatory factors. MSC polarized with pro-inflammatory cytokines showed a more robust pro-angiogenic effect in fibrin gel bead 3D angiogenesis assay. Further, we evaluated the possibility of paracrine effects of MSCs on the polarization of intact macrophages. Polarization efficiency was assesed by expression of M1/M2 phenotype markers CD80 and CD206. We showed that conditioned media from MSC preincubated in the presence of IL-4 cause an increase in CD206 expression similar to that observed in M2 macrophages. Conditioned media from MSC polarized in the presence of LPS or TNF-α increased the expression of CD80 antigen in macrophages, similar to that observed in M1 macrophages. In other cases, a pronounced paracrine effect of MSC on the polarization of macrophages was not detected. Thus, our study showed that the polarization of MSC along the pro-inflammatory or anti-inflammatory pathway allows us to obtain cell subpopulations that have a multidirectional modulating effect on the polarization of macrophages. (RFBR grants 20-015-00405 and 18-015-00398.)

Keywords: angiogenesis, cytokines, mesenchymal, polarization, inflammation

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233 Breast Cancer: The Potential of miRNA for Diagnosis and Treatment

Authors: Abbas Pourreza

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MicroRNAs (miRNAs) are small single-stranded non-coding RNAs. They are almost 18-25 nucleotides long and very conservative through evolution. They are involved in adjusting the expression of numerous genes due to the existence of a complementary region, generally in the 3' untranslated regions (UTR) of target genes, against particular mRNAs in the cell. Also, miRNAs have been proven to be involved in cell development, differentiation, proliferation, and apoptosis. More than 2000 miRNAs have been recognized in human cells, and these miRNAs adjust approximately one-third of all genes in human cells. Dysregulation of miRNA originated from abnormal DNA methylation patterns of the locus, cause to down-regulated or overexpression of miRNAs, and it may affect tumor formation or development of it. Breast cancer (BC) is the most commonly identified cancer, the most prevalent cancer (23%), and the second-leading (14%) mortality in all types of cancer in females. BC can be classified based on the status (+/−) of the hormone receptors, including estrogen receptor (ER), progesterone receptor (PR), and the Receptor tyrosine-protein kinase erbB-2 (ERBB2 or HER2). Currently, there are four main molecular subtypes of BC: luminal A, approximately 50–60 % of BCs; luminal B, 10–20 %; HER2 positive, 15–20 %, and 10–20 % considered Basal (triple-negative breast cancer (TNBC)) subtype. Aberrant expression of miR-145, miR-21, miR-10b, miR-125a, and miR-206 was detected by Stem-loop real-time RT-PCR in BC cases. Breast tumor formation and development may result from down-regulation of a tumor suppressor miRNA such as miR-145, miR-125a, and miR-206 and/or overexpression of an oncogenic miRNA such as miR-21 and miR-10b. MiR-125a, miR-206, miR-145, miR-21, and miR-10b are hugely predicted to be new tumor markers for the diagnosis and prognosis of BC. MiR-21 and miR-125a could play a part in the treatment of HER-2-positive breast cancer cells, while miR-145 and miR-206 could speed up the evolution of cure techniques for TNBC. To conclude, miRNAs will be presented as hopeful molecules to be used in the primary diagnosis, prognosis, and treatment of BC and battle as opposed to its developed drug resistance.

Keywords: breast cancer, HER2 positive, miRNA, TNBC

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232 Clinical Relevance of TMPRSS2-ERG Fusion Marker for Prostate Cancer

Authors: Shalu Jain, Anju Bansal, Anup Kumar, Sunita Saxena

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Objectives: The novel TMPRSS2:ERG gene fusion is a common somatic event in prostate cancer that in some studies is linked with a more aggressive disease phenotype. Thus, this study aims to determine whether clinical variables are associated with the presence of TMPRSS2:ERG-fusion gene transcript in Indian patients of prostate cancer. Methods: We evaluated the clinical variables with presence and absence of TMPRSS2:ERG gene fusion in prostate cancer and BPH association of clinical patients. Patients referred for prostate biopsy because of abnormal DRE or/and elevated sPSA were enrolled for this prospective clinical study. TMPRSS2:ERG mRNA copies in samples were quantified using a Taqman chemistry by real time PCR assay in prostate biopsy samples (N=42). The T2:ERG assay detects the gene fusion mRNA isoform TMPRSS2 exon1 to ERG exon4. Results: Histopathology report has confirmed 25 cases as prostate cancer adenocarcinoma (PCa) and 17 patients as benign prostate hyperplasia (BPH). Out of 25 PCa cases, 16 (64%) were T2: ERG fusion positive. All 17 BPH controls were fusion negative. The T2:ERG fusion transcript was exclusively specific for prostate cancer as no case of BPH was detected having T2:ERG fusion, showing 100% specificity. The positive predictive value of fusion marker for prostate cancer is thus 100% and the negative predictive value is 65.3%. The T2:ERG fusion marker is significantly associated with clinical variables like no. of positive cores in prostate biopsy, Gleason score, serum PSA, perineural invasion, perivascular invasion and periprostatic fat involvement. Conclusions: Prostate cancer is a heterogeneous disease that may be defined by molecular subtypes such as the TMPRSS2:ERG fusion. In the present prospective study, the T2:ERG quantitative assay demonstrated high specificity for predicting biopsy outcome; sensitivity was similar to the prevalence of T2:ERG gene fusions in prostate tumors. These data suggest that further improvement in diagnostic accuracy could be achieved using a nomogram that combines T2:ERG with other markers and risk factors for prostate cancer.

Keywords: prostate cancer, genetic rearrangement, TMPRSS2:ERG fusion, clinical variables

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231 Exercise and Aging Process Related to Oxidative Stress

Authors: B. Dejanova, S. Petrovska, L. Todorovska, J. Pluncevic, S. Mancevska, V. Antevska, E. Sivevska, I. Karagjozova

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Introduction: Aging process is mainly related to endothelial function which may be impaired by oxidative stress (OS). Exercise is known to be beneficial to aging process, which may improve health and prevent appearance of chronic diseases in elderly. The aim of the study was to investigate the OS markers related to exercise. Methods: A number of 80 subjects (healthy volunteers) were examined (38 male and 32 female), divided in 3 age groups: group I ≤ 30 years (n=24); group II – 31-50 years (n=24); group III - ≥ 51 year (n=32). Each group was divided to subgroups of sedentary subjects (SS) and subjects who exercise (SE). Group I: SS (n=11), SE (n=13); group II: SS (n=13), SE (n=10); group III: SS (n=23) SE (n=9). Lipid peroxidation (LP) as a fluorimetric method with thiobarbituric acid was used to estimate OS. Antioxidative status was determined by cell antioxidants such as enzymes - superoxide dismutase (SOD), glutathione peroxidase (GPx) and glucose 6 phosphate (G-6-PD); and by extra cell antioxidants such as glutathione reductase (GR), nitric oxide (NO) and total antioxidant capacity (TAC). Results: Increased values of LP were noticed along the aging process: group I – 3.30±0.3 µmol/L; group II – 3.91±0.2 µmol/L; group III – 3.94±0.8 µmol/L (p<0.05), while no statistical significance was found between male and female subjects. Statistical significance for OS was not found between SS and SE in group I as it was found in group II (p<0.05) and in group III (p<0.01). No statistical significance was found for all cell antioxidants and GR within the groups, while NO and TAC showed lower values in SS compared to SE in II (p<0.05) and in group III (p<0.05). Discussion and conclusion: Aging process showed increased OS which may be either due to impaired function of scavengers of free radicals or due to their enormous production. Well balanced exercise might be one of the factors that keep the integrity of blood vessel endothelium which slows down the aging process. Possible mechanism of exercise beneficial influence is shear stress by upregulation of genes coding for nitric oxide bioavailability. Thus, due to obtained results we may conclude that OS is found to be diminished in the subject groups who perform exercise.

Keywords: oxidative stress, aging process, exercise, endothelial function

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230 Hepatoprotective Assessment of L-Ascorbate 1-(2-Hydroxyethyl)-4,6-Dimethyl-1, 2-Dihydropyrimidine-2-on in Toxic Liver Damage Test

Authors: Vladimir Zobov, Nail Nazarov, Alexandra Vyshtakalyuk, Vyacheslav Semenov, Irina Galyametdinova, Vladimir Reznik

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The aim of this study was to investigate hepatoprotective properties of the Xymedon derivative L-ascorbate 1- (2-hydroxyethyl)-4,6-dimethyl-1,2-dihydropyrimidine-2-one (XD), which exhibits high efficiency as actoprotector. The study was carried out on 68 male albino rats weighing 250-400 g using preventive exposure to the test preparation. Effectiveness of XD win comparison with effectiveness of Xymedon (original substance) after administration of the compounds in identical doses. Maximum dose was 20 mg/kg. The animals orally received Xymedon or its derivative in doses of 10 and 20 mg/kg over 4 days. In 1-1.5 h after drug administration, CCl4 in vegetable oil (1:1) in a dose of 2 ml/kg. Controls received CCl4 but without hepatoprotectors. Intact control group consisted of rats, not receiving CCl4 or other compounds. The next day after the last administration of CCl4 and compounds under study animals were dehematized under ether anesthesia, blood and liver samples were taken for biochemical and histological analysis. Xymedon and XD administered according to the preventice scheme, exerted hepatoprotective effects: Xymedon — in the dose of 20 mg/kg, XD — in doses of 10 and 20 mg/kg. The drugs under study had different effects on liver condition, affected by induction with CCl4. Xymedon had a more pronounced effect both on the ALT level, which can be elevated not only due to destructive changes in hepatocytes, but also as a cholestasis manifestation, and on the serum total protein level, which reflects protein synthesis in liver. XD had a more pronounced effect on AST level, which is one of the markers of hepatocyte damage. Lower effective dose of XD — 10 mg/kg, compared to Xymedon effective according to, and its pronounced effect on AST, the hepatocyte cytolysis marker, is indicative of its higher preventive effectiveness, compared to Xymedon. This work was performed with the financial support of Russian Science Foundation (grant No: 14-50-00014).

Keywords: hepatoprotectors, pyrimidine derivatives, toxic liver damage, xymedon

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229 The Lighthouse Project: Recent Initiatives to Navigate Australian Families Safely Through Parental Separation

Authors: Kathryn McMillan

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A recent study of 8500 adult Australians aged 16 and over revealed 62% had experienced childhood maltreatment. In response to multiple recommendations by bodies such as the Australian Law Reform Commission, parliamentary reports and stakeholder input, a number of key initiatives have been developed to grapple with the difficulties of a federal-state system and to screen and triage high-risk families navigating their way through the court system. The Lighthouse Project (LHP) is a world-first initiative of the Federal Circuit and Family Courts in Australia (FCFOCA) to screen family law litigants for major risk factors, including family violence, child abuse, alcohol or substance abuse and mental ill-health at the point of filing in all applications that seek parenting orders. It commenced on 7 December 2020 on a pilot basis but has now been expanded to 15 registries across the country. A specialist risk screen, Family DOORS, Triage has been developed – focused on improving the safety and wellbeing of families involved in the family law system safety planning and service referral, and ¬ differentiated case management based on risk level, with the Evatt List specifically designed to manage the highest risk cases. Early signs are that this approach is meeting the needs of families with multiple risks moving through the Court system. Before the LHP, there was no data available about the prevalence of risk factors experienced by litigants entering the family courts and it was often assumed that it was the litigation process that was fueling family violence and other risks such as suicidality. Data from the 2022 FCFCOA annual report indicated that in parenting proceedings, 70% alleged a child had been or was at risk of abuse, 80% alleged a party had experienced Family Violence, 74 % of children had been exposed to Family Violence, 53% alleged through substance misuse by party children had caused or was at risk of causing harm to children and 58% of matters allege mental health issues of a party had caused or placed a child at risk of harm. Those figures reveal the significant overlap between child protection and family violence, both of which are under the responsibility of state and territory governments. Since 2020, a further key initiative has been the co-location of child protection and police officials amongst a number of registries of the FCFOCA. The ability to access in a time-effective way details of family violence or child protection orders, weapons licenses, criminal convictions or proceedings is key to managing issues across the state and federal divide. It ensures a more cohesive and effective response to family law, family violence and child protection systems.

Keywords: child protection, family violence, parenting, risk screening, triage.

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228 Pathogenic Effects of IgG and IgM Apoptotic Cell-Reactive Monoclonal Auto-Antibodies on Innate and Adaptive Immunity in Lupus

Authors: Monika Malik, Pooja Arora, Ruchi Sachdeva, Vishnampettai G. Ramachandran, Rahul Pal

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Apoptotic debris is believed to be the antigenic trigger in lupus. Whether such debris and autoantibodies induced in lupus-prone mice which specifically recognize its constituents can mediate differential effects on innate and humoral responses in such mice was assessed. The influence of apoptotic blebs and apoptotic cell-reactive monoclonal antibodies on phenotypic markers expressed on bone marrow-derived dendritic cells (BMDCs) and secreted cytokines were evaluated. Sera from lupus-prone and healthy mice immunized with the antibodies were analyzed for anti-self reactivity. Apoptotic blebs, as well as somatically-mutated IgG and non-mutated IgM apoptotic-cell reactive monoclonal antibodies, induced the preferential maturation of BMDCs derived from lupus-prone mice relative to BMDCs derived from healthy mice; antibody specificity and cell genotype both influenced the secretion of inflammatory cytokines. Immunization of lupus-prone mice with IgM and IgG antibodies led to hypergammaglobulinemia; elicited antibodies were self-reactive, and exhibited enhanced recognition of lupus-associated autoantigens (dsDNA, Ro60, RNP68, and Sm) in comparison with adjuvant-induced sera. While ‘natural’ IgM antibodies are believed to contribute to immune homeostasis, this study reveals that apoptotic cell-reactive IgM antibodies can promote inflammation and drive anti-self responses in lupus. Only in lupus-prone mice did immunization with IgG auto-antibodies enhance the kinetics of humoral anti-self responses, resulting in advanced-onset glomerulosclerosis. This study reveals that preferential innate and humoral recognition of the products of cell death in an autoimmune milieu influences the indices associated with lupus pathology.

Keywords: antigen spreading, apoptotic cell-reactive pathogenic IgG, and IgM autoantibodies, glomerulosclerosis, lupus

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227 Effects of Acupuncture Treatment in Gait Parameters in Parkinson's Disease

Authors: Catarina Isabel Ramos Pereira, Jorge Machado, Begona Alonso Criado, Maria João Santos

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Introduction: Gait disorders are one of the symptoms that have severe implications on the quality of life in Parkinson's disease (PD). Currently, there is no therapy to reverse or treat this condition. None of the drugs used in conventional medical treatment is entirely efficient, and all have a high incidence of side effects. Acupuncture treatment is believed to improve motor ability, but there is still little scientific evidence in individuals with PD. Aim: The aim of the study is to investigate the acute effect of acupuncture on gait parameters in Parkinson's disease. Methods: This is a randomized and controlled crossover study. The same individual patient was part of both the experimental (real acupuncture) and control group (false acupuncture/sham), and the sequence was randomized. Gait parameters were measured at two different moments, before and after treatment, using four force platforms as well as the collection of 3D markers positions taken by 11 cameras. Images were quantitatively analyzed using Qualisys Track Manager software that let us extract data related to the quality of gait and balance. Seven patients with the diagnosis of Parkinson's disease were included in the study. Results: Statistically significant differences were found in gait speed (p = 0.016), gait cadence (p = 0.006), support base width (p = 0.0001), medio-lateral oscillation (p = 0.017), left-right step length (p = 0.0002), and stride length: right-right (p = 0.0000) and left-left (p = 0.0018), time of left support phase (p = 0.029), right support phase (p = 0.025) and double support phase (p = 0.015), between the initial and final moments for the experimental group. Differences in right-left stride length were found for both groups. Conclusion: Our results show that acupuncture could enhance gait in Parkinson's disease patients. Deep research involving a larger number of volunteers should be accomplished to validate these encouraging findings.

Keywords: acupuncture, traditional Chinese medicine, Parkinson's disease, gait

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226 Detection of Bcl2 Polymorphism in Patient with Hepatocellular carcinoma

Authors: Mohamed Abdel-Hamid, Olfat Gamil Shaker, Doha El-Sayed Ellakwa, Eman Fathy Abdel-Maksoud

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Introduction: Despite advances in the knowledge of the molecular virology of hepatitis C virus (HCV), the mechanisms of hepatocellular injury in HCV infection are not completely understood. Hepatitis C viral infection (HCV) influences the susceptibility to apoptosis. This could lead to insufficient antiviral immune response and persistent viral infection. Aim of this study: was to examine whether BCL-2 gene polymorphism at codon 43 (+127G/A or Ala43Thr) has an impact on development of hepatocellular carcinoma caused by chronic hepatitis C Egyptian patients. Subjects and Methods: The study included three groups; group 1: composing of 30 patients with hepatocellular carcinoma (HCC), group 2 composing of 30 patients with HCV, group 3 composing of 30 healthy subjects matching the same age and socioeconomic status were taken as a control group. Gene polymorphism of BCL2 (Ala43Thr) were evaluated by PCR-RFLP technique and measured for all patients and controls. Results: The summed 43Thr genotype was more frequent and statistically significant in HCC patients as compared to control group. This genotype of BCL2 gene may inhibit the programmed cell death which leads to disturbance in tissue and cells homeostasis and reduction in immune regulation. This result leads to viral replication and HCV persistence. Moreover, virus produces variety of mechanisms to block genes participated in apoptosis. This mechanism proves that HCV patients who have 43Thr genotype are more susceptible to HCC. Conclusion: The data suggest for the first time that the BCL2 polymorphism is associated with the susceptibility to HCC in Egyptian populations and might be used as molecular markers for evaluating HCC risk. This study clearly demonstrated that Chronic HCV exhibit a deregulation of apoptosis with the disease progression. This provides an insight into the pathogenesis of chronic HCV infection, and may contribute to the therapy.

Keywords: BCL2 gene, Hepatitis C Virus, Hepatocellular carcinoma, sensitivity, specificity, apoptosis

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