Search results for: prostate epithelial markers
81 Aloe vera Prevents Injuries Induced by Whole Body X-ray Irradiation in Rodents
Authors: Shashi Bala, Neha A. Chugh, Subhash C. Bansal, Mohal L. Garg, Ashwani Koul
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Purpose: The present study was designed to evaluate the radioprotective efficacy of Aloe vera from whole body X-ray exposure in rodents. Materials and Methods: For this purpose, after on week’s acclimatization, male balb/c mice procured from Central Animal House, Panjab University, Chandigarh (India), were divided into four groups: Group I mice served as control. Group II mice were orally administrated Aloe vera pulp extract (50 mg/ kg body weight) on alternate days for 30 days. Group III mice were subjected to whole body X-ray irradiation to cumulative dose of 2Gy (0.258Gy twice a day for four days in the last week). Group IV animals were pretreated with Aloe vera pulp extract on alternate days as in Group II and in the last week of the study, they were exposed to X-ray as in Group III. Results: Spleen of X-ray irradiated mice showed histopathological alterations accompanied with enhanced activity of lactate dehydrogenase (LDH) in serum. Elevated levels of reactive oxygen species (ROS), lipid peroxidation (LPO), enhanced activities in Glutathione based enzymes such as Glutathione peroxidase (GSH-Px), Glutathione reductase (GR), Catalase (CAT), Superoxide dismutase (SOD) associated with depletion in reduced Glutathione (GSH) concentration were observed after X-ray exposure in blood plasma and spleen.. Pro-inflammatory cytokines like tumor necrosis factors (TNF-α) and Inteleukin-6 (IL-6) levels were also found to be enhanced in serum of irradiated mice. Irradiation-induced significant elevation in Total leucocyte counts (TLC), neutrophil counts and decline in platelet counts, associated with unaltered levels of red blood cell counts (RBC’s) and haemoglobin (Hb) in various treatment groups. Clastogenic damage and apoptosis was also found to be increase in splenic tissue of X-ray exposed mice as assessed by micronucleus and TUNEL assay. However, X-ray irradiated animals administered with Aloe vera revealed significant improvement in levels of ROS/ LPO, LDH activity, and antioxidant mechanism. Aloe vera pretreated animals exhibited less severe damage, and early recovery in micronucleated cells, hematological parameters, apoptotic cells and inflammatory markers as compared to X-ray exposed mice. Conclusion: These results indicate that the radioprotective potential of Aloe vera against X-ray induced damage. This may be due to its free radical scavenging, antioxidant, anti-apoptotic and anti-inflammatory properties.Keywords: aloe vera, antioxidant defense system, lactate dehydrogenase (LDH), micronucleus assay, x-ray
Procedia PDF Downloads 19280 Detection of Alzheimer's Protein on Nano Designed Polymer Surfaces in Water and Artificial Saliva
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
Procedia PDF Downloads 29179 Association between TNF-α and Its Receptor TNFRSF1B Polymorphism with Pulmonary Tuberculosis in Tomsk, Russia Federation
Authors: K. A. Gladkova, N. P. Babushkina, E. Y. Bragina
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Purpose: Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the major public health problems worldwide. It is clear that the immune response to M. tuberculosis infection is a relationship between inflammatory and anti-inflammatory responses in which Tumour Necrosis Factor-α (TNF-α) plays key roles as a pro-inflammatory cytokine. TNF-α involved in various cell immune responses via binding to its two types of membrane-bound receptors, TNFRSF1A and TNFRSF1B. Importantly, some variants of the TNFRSF1B gene have been considered as possible markers of host susceptibility to TB. However, the possible impact of such TNF-α and its receptor genes polymorphism on TB cases in Tomsk is missing. Thus, the purpose of our study was to investigate polymorphism of TNF-α (rs1800629) and its receptor TNFRSF1B (rs652625 and rs525891) genes in population of Tomsk and to evaluate their possible association with the development of pulmonary TB. Materials and Methods: The population distribution features of genes polymorphisms were investigated and made case-control study based on group of people from Tomsk. Human blood was collected during routine patients examination at Tomsk Regional TB Dispensary. Altogether, 234 TB-positive patients (80 women, 154 men, average age is 28 years old) and 205 health-controls (153 women, 52 men, average age is 47 years old) were investigated. DNA was extracted from blood plasma by phenol-chloroform method. Genotyping was carried out by a single-nucleotide-specific real-time PCR assay. Results: First, interpopulational comparison was carried out between healthy individuals from Tomsk and available data from the 1000 Genomes project. It was found that polymorphism rs1800629 region demonstrated that Tomsk population was significantly different from Japanese (P = 0.0007), but it was similar with the following Europeans subpopulations: Italians (P = 0.052), Finns (P = 0.124) and British (P = 0.910). Polymorphism rs525891 clear demonstrated that group from Tomsk was significantly different from population of South Africa (P = 0.019). However, rs652625 demonstrated significant differences from Asian population: Chinese (P = 0.03) and Japanese (P = 0.004). Next, we have compared healthy individuals versus patients with TB. It was detected that no association between rs1800629, rs652625 polymorphisms, and positive TB cases. Importantly, AT genotype of polymorphism rs525891 was significantly associated with resistance to TB (odds ratio (OR) = 0.61; 95% confidence interval (CI): 0.41-0.9; P < 0.05). Conclusion: To the best of our knowledge, the polymorphism of TNFRSF1B (rs525891) was associated with TB, while genotype AT is protective [OR = 0.61] in Tomsk population. In contrast, no significant correlation was detected between polymorphism TNF-α (rs1800629) and TNFRSF1B (rs652625) genes and alveolar TB cases among population of Tomsk. In conclusion, our data expands the molecular particularities associated with TB. The study was supported by the grant of the Russia for Basic Research #15-04-05852.Keywords: polymorphism, tuberculosis, TNF-α, TNFRSF1B gene
Procedia PDF Downloads 18078 Risk Factors for Determining Anti-HBcore to Hepatitis B Virus Among Blood Donors
Authors: Tatyana Savchuk, Yelena Grinvald, Mohamed Ali, Ramune Sepetiene, Dinara Sadvakassova, Saniya Saussakova, Kuralay Zhangazieva, Dulat Imashpayev
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Introduction. The problem of viral hepatitis B (HBV) takes a vital place in the global health system. The existing risk of HBV transmission through blood transfusions is associated with transfusion of blood taken from infected individuals during the “serological window” period or from patients with latent HBV infection, the marker of which is anti-HBcore. In the absence of information about other markers of hepatitis B, the presence of anti-HBcore suggests that a person may be actively infected or has suffered hepatitis B in the past and has immunity. Aim. To study the risk factors influencing the positive anti-HBcore indicators among the donor population. Materials and Methods. The study was conducted in 2021 in the Scientific and Production Center of Transfusiology of the Ministry of Healthcare in Kazakhstan. The samples taken from blood donors were tested for anti-HBcore, by CLIA on the Architect i2000SR (ABBOTT). A special questionnaire was developed for the blood donors’ socio-demographic characteristics. Statistical analysis was conducted by the R software (version 4.1.1, USA, 2021). Results.5709 people aged 18 to 66 years were included in the study, the proportion of men and women was 68.17% and 31.83%, respectively. The average age of the participants was 35.7 years. A weighted multivariable mixed effects logistic regression analysis showed that age (p<0.001), ethnicity (p<0.05), and marital status (p<0.05) were statistically associated with anti-HBcore positivity. In particular, analysis adjusting for gender, nationality, education, marital status, family history of hepatitis, blood transfusion, injections, and surgical interventions, with a one-year increase in age (adjOR=1.06, 95%CI:1.05-1.07), showed an 6% growth in odds of having anti-HBcore positive results. Those who were russian ethnicity (adjOR=0.65, 95%CI:0.46-0.93) and representatives of other nationality groups (adjOR=0.56, 95%CI:0.37-0.85) had lower odds of having anti-HBcore when compared to Kazakhs when controlling for other covariant variables. Among singles, the odds of having a positive anti-HBcore were lower by 29% (adjOR = 0.71, 95%CI:0.57-0.89) compared to married participants when adjusting for other variables. Conclusions.Kazakhstan is one of the countries with medium endemicity of HBV prevalence (2%-7%). Results of the study demonstrated the possibility to form a profile of risk factors (age, nationality, marital status). Taking into account the data, it is recommended to increase attention to donor questionnaires by adding leading questions and to improve preventive measures to prevent HBV. Funding. This research was supported by a grant from Abbott Laboratories.Keywords: anti-HBcore, blood donor, donation, hepatitis B virus, occult hepatitis
Procedia PDF Downloads 10877 Prediction of Outcome after Endovascular Thrombectomy for Anterior and Posterior Ischemic Stroke: ASPECTS on CT
Authors: Angela T. H. Kwan, Wenjun Liang, Jack Wellington, Mohammad Mofatteh, Thanh N. Nguyen, Pingzhong Fu, Juanmei Chen, Zile Yan, Weijuan Wu, Yongting Zhou, Shuiquan Yang, Sijie Zhou, Yimin Chen
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Background: Endovascular Therapy (EVT)—in the form of mechanical thrombectomy—following intravenous thrombolysis is the standard gold treatment for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). It is well established that an ASPECTS ≥ 7 is associated with an increased likelihood of positive post-EVT outcomes, as compared to an ASPECTS < 7. There is also prognostic utility in coupling posterior circulation ASPECTS (pc-ASPECTS) with magnetic resonance imaging for evaluating the post-EVT functional outcome. However, the value of pc-ASPECTS applied to CT must be explored further to determine its usefulness in predicting functional outcomes following EVT. Objective: In this study, we aimed to determine whether pc-ASPECTS on CT can predict post-EVT functional outcomes among patients with AIS due to LVO. Methods: A total of 247 consecutive patients aged 18 and over receiving EVT for LVO-related AIS were recruited into a prospective database. The data were retrospectively analyzed between March 2019 to February 2022 from two comprehensive tertiary care stroke centers: Foshan Sanshui District People’s Hospital and First People's Hospital of Foshan in China. Patient parameters included EVT within 24hrs of symptom onset, premorbid modified Rankin Scale (mRS) ≤ 2, presence of distal and terminal cerebral blood vessel occlusion, and subsequent 24–72-hour post-stroke onset CT scan. Univariate comparisons were performed using the Fisher exact test or χ2 test for categorical variables and the Mann–Whitney U test for continuous variables. A p-value of ≤ 0.05 was statistically significant. Results: A total of 247 patients met the inclusion criteria; however, 3 were excluded due to the absence of post-CTs and 8 for pre-EVT ASPECTS < 7. Overall, 236 individuals were examined: 196 anterior circulation ischemic strokes and 40 posterior strokes of basilar artery occlusion. We found that both baseline post- and pc-ASPECTS ≥ 7 serve as strong positive markers of favorable outcomes at 90 days post-EVT. Moreover, lower rates of inpatient mortality/hospice discharge, 90-day mortality, and 90-day poor outcome were observed. Moreover, patients in the post-ASPECTS ≥ 7 anterior circulation group had shorter door-to-recanalization time (DRT), puncture-to-recanalization time (PRT), and last known normal-to-puncture-time (LKNPT). Conclusion: Patients of anterior and posterior circulation ischemic strokes with baseline post- and pc-ASPECTS ≥ 7 may benefit from EVT.Keywords: endovascular therapy, thrombectomy, large vessel occlusion, cerebral ischemic stroke, ASPECTS
Procedia PDF Downloads 11276 Generating a Multiplex Sensing Platform for the Accurate Diagnosis of Sepsis
Authors: N. Demertzis, J. L. Bowen
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Sepsis is a complex and rapidly evolving condition, resulting from uncontrolled prolonged activation of host immune system due to pathogenic insult. The aim of this study is the development of a multiplex electrochemical sensing platform, capable of detecting both pathogen associated and host immune markers to enable the rapid and definitive diagnosis of sepsis. A combination of aptamers and molecular imprinting approaches have been employed to generate sensing systems for lipopolysaccharide (LPS), c-reactive protein (CRP) and procalcitonin (PCT). Gold working electrodes were mechanically polished and electrochemically cleaned with 0.1 M sulphuric acid using cyclic voltammetry (CV). Following activation, a self-assembled monolayer (SAM) was generated, by incubating the electrodes with a thiolated anti-LPS aptamer / dithiodibutiric acid (DTBA) mixture (1:20). 3-aminophenylboronic acid (3-APBA) in combination with the anti-LPS aptamer was used for the development of the hybrid molecularly imprinted sensor (apta-MIP). Aptasensors, targeting PCT and CRP were also fabricated, following the same approach as in the case of LPS, with mercaptohexanol (MCH) replacing DTBA. In the case of the CRP aptasensor, the SAM was formed following incubation of a 1:1 aptamer: MCH mixture. However, in the case of PCT, the SAM was formed with the aptamer itself, with subsequent backfilling with 1 μM MCH. The binding performance of all systems has been evaluated using electrochemical impedance spectroscopy. The apta-MIP’s polymer thickness is controlled by varying the number of electropolymerisation cycles. In the ideal number of polymerisation cycles, the polymer must cover the electrode surface and create a binding pocket around LPS and its aptamer binding site. Less polymerisation cycles will create a hybrid system which resembles an aptasensor, while more cycles will be able to cover the complex and demonstrate a bulk polymer-like behaviour. Both aptasensor and apta-MIP were challenged with LPS and compared to conventional imprinted (absence of aptamer from the binding site, polymer formed in presence of LPS) and non-imprinted polymers (NIPS, absence of LPS whilst hybrid polymer is formed). A stable LPS aptasensor, capable of detecting down to 5 pg/ml of LPS was generated. The apparent Kd of the system was estimated at 17 pM, with a Bmax of approximately 50 pM. The aptasensor demonstrated high specificity to LPS. The apta-MIP demonstrated superior recognition properties with a limit of detection of 1 fg/ml and a Bmax of 100 pg/ml. The CRP and PCT aptasensors were both able to detect down to 5 pg/ml. Whilst full binding performance is currently being evaluated, there is none of the sensors demonstrate cross-reactivity towards LPS, CRP or PCT. In conclusion, stable aptasensors capable of detecting LPS, PCT and CRP at low concentrations have been generated. The realisation of a multiplex panel such as described herein, will effectively contribute to the rapid, personalised diagnosis of sepsis.Keywords: aptamer, electrochemical impedance spectroscopy, molecularly imprinted polymers, sepsis
Procedia PDF Downloads 12575 The Effects of Alpha-Lipoic Acid Supplementation on Post-Stroke Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Hamid Abbasi, Neda Jourabchi, Ranasadat Abedi, Kiarash Tajernarenj, Mehdi Farhoudi, Sarvin Sanaie
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Background: Alpha lipoic acid (ALA), fat- and water-soluble, coenzyme with sulfuret content, has received considerable attention for its potential therapeutic role in diabetes, cardiovascular diseases, cancers, and central nervous disease. This investigation aims to evaluate the probable protective effects of ALA in stroke patients. Methods: Based on Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, This meta-analysis was performed. The PICO criteria for this meta-analysis were as follows: Population/Patients (P: stroke patients); Intervention (I: ALA); Comparison (C: control); Outcome (O: blood glucose, lipid profile, oxidative stress, inflammatory factors).In addition, Studies that were excluded from the analysis consisted of in vitro, in vivo, and ex vivo studies, case reports, quasi-experimental studies. Scopus, PubMed, Web of Science, EMBASE databases were searched until August 2023. Results: Of 496 records that were screened in the title/abstract stage, 9 studies were included in this meta-analysis. The sample sizes in the included studies vary between 28 and 90. The result of risk of bias was performed via risk of bias (RoB) in randomized-controlled trials (RCTs) based on the second version of the Cochrane RoB assessment tool. 8 studies had a definitely high risk of bias. Discussion: To the best of our knowledge, The present meta-analysis is the first study addressing the effectiveness of ALA supplementation in enhancing post-stroke metabolic markers, including lipid profile, oxidative stress, and inflammatory indices. It is imperative to acknowledge certain potential limitations inherent in this study. First of all, type of treatment (oral or intravenous infusion) could alter the bioavailability of ALA. Our study had restricted evidence regarding the impact of ALA supplementation on included outcomes. Therefore, further research is warranted to develop into the effects of ALA specifically on inflammation and oxidative stress. Funding: The research protocol was approved and supported by the Student Research Committee, Tabriz University of Medical Sciences (grant number: 72825). Registration: This study was registered in the International prospective register of systematic reviews (PROSPERO ID: CR42023461612).Keywords: alpha-lipoic acid, lipid profile, blood glucose, inflammatory factors, oxidative stress, meta-analysis, post-stroke
Procedia PDF Downloads 6374 A Clinical Cutoff to Identify Metabolically Unhealthy Obese and Normal-Weight Phenotype in Young Adults
Authors: Lívia Pinheiro Carvalho, Luciana Di Thommazo-Luporini, Rafael Luís Luporini, José Carlos Bonjorno Junior, Renata Pedrolongo Basso Vanelli, Manoel Carneiro de Oliveira Junior, Rodolfo de Paula Vieira, Renata Trimer, Renata G. Mendes, Mylène Aubertin-Leheudre, Audrey Borghi-Silva
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Rationale: Cardiorespiratory fitness (CRF) and functional capacity in young obese and normal-weight people are associated with metabolic and cardiovascular diseases and mortality. However, it remains unclear whether their metabolically healthy (MH) or at risk (AR) phenotype influences cardiorespiratory fitness in this vulnerable population such as obese adults but also in normal-weight people. HOMA insulin resistance index (HI) and leptin-adiponectin ratio (LA) are strong markers for characterizing those phenotypes that we hypothesized to be associated with physical fitness. We also hypothesized that an easy and feasible exercise test could identify a subpopulation at risk to develop metabolic and related disorders. Methods: Thirty-nine sedentary men and women (20-45y; 18.5Keywords: aerobic capacity, exercise, fitness, metabolism, obesity, 6MST
Procedia PDF Downloads 35473 Lateral Retroperitoneal Transpsoas Approach: A Practical Minimal Invasive Surgery Option for Treating Pyogenic Spondylitis of the Lumbar Vertebra
Authors: Sundaresan Soundararajan, Chor Ngee Tan
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Introduction: Pyogenic spondylitis, otherwise treated conservatively with long term antibiotics, would require surgical debridement and reconstruction in about 10% to 20% of cases. The classical approach adopted many surgeons have always been anterior approach in ensuring thorough and complete debridement. This, however, comes with high rates of morbidity due to the nature of its access. Direct lateral retroperitoneal approach, which has been growing in usage in degenerative lumbar diseases, has the potential in treating pyogenic spondylitis with its ease of approach and relatively low risk of complications. Aims/Objectives: The objective of this study was to evaluate the effectiveness and clinical outcome of using lateral approach surgery in the surgical management of pyogenic spondylitis of the lumbar spine. Methods: Retrospective chart analysis was done on all patients who presented with pyogenic spondylitis (lumbar discitis/vertebral osteomyelitis) and had undergone direct lateral retroperitoneal lumbar vertebral debridement and posterior instrumentation between 2014 and 2016. Data on blood loss, surgical operating time, surgical complications, clinical outcomes and fusion rates were recorded. Results: A total of 6 patients (3 male and 3 female) underwent this procedure at a single institution by a single surgeon during the defined period. One patient presented with infected implant (PLIF) and vertebral osteomyelitis while the other five presented with single level spondylodiscitis. All patients underwent lumbar debridement, iliac strut grafting and posterior instrumentation (revision of screws for infected PLIF case). The mean operating time was 308.3 mins for all 6 cases. Mean blood loss was reported at 341cc (range from 200cc to 600cc). Presenting symptom of back pain resolved in all 6 cases while 2 cases that presented with lower limb weakness had improvement of neurological deficits. One patient had dislodged strut graft while performing posterior instrumentation and needed graft revision intraoperatively. Infective markers normalized for all patients subsequently. All subjects also showed radiological evidence of fusion on 6 months follow up. Conclusions: Lateral approach in treating pyogenic spondylitis is a viable option as it allows debridement and reconstruction without the risk that comes with other anterior approaches. It allows efficient debridement, short surgical time, moderate blood loss and low risk of vascular injuries. Clinical outcomes and fusion rates by this approach also support its use as practical MIS option surgery for such infection cases.Keywords: lateral approach, minimally invasive, pyogenic spondylitis, XLIF
Procedia PDF Downloads 17772 Determinants of Quality of Life in Patients with Atypical Prarkinsonian Syndromes: 1-Year Follow-Up Study
Authors: Tatjana Pekmezovic, Milica Jecmenica-Lukic, Igor Petrovic, Vladimir Kostic
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Background: A group of atypical parkinsonian syndromes (APS) includes a variety of rare neurodegenerative disorders characterized by reduced life expectancy, increasing disability, and considerable impact on health-related quality of life (HRQoL). Aim: In this study we wanted to answer two questions: a) which demographic and clinical factors are main contributors of HRQoL in our cohort of patients with APS, and b) how does quality of life of these patients change over 1-year follow-up period. Patients and Methods: We conducted a prospective cohort study in hospital settings. The initial study comprised all consecutive patients who were referred to the Department of Movement Disorders, Clinic of Neurology, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade (Serbia), from January 31, 2000 to July 31, 2013, with the initial diagnoses of ‘Parkinson’s disease’, ‘parkinsonism’, ‘atypical parkinsonism’ and ‘parkinsonism plus’ during the first 8 months from the appearance of first symptom(s). The patients were afterwards regularly followed in 4-6 month intervals and eventually the diagnoses were established for 46 patients fulfilling the criteria for clinically probable progressive supranuclear palsy (PSP) and 36 patients for probable multiple system atrophy (MSA). The health-related quality of life was assessed by using the SF-36 questionnaire (Serbian translation). Hierarchical multiple regression analysis was conducted to identify predictors of composite scores of SF-36. The importance of changes in quality of life scores of patients with APS between baseline and follow-up time-point were quantified using Wilcoxon Signed Ranks Test. The magnitude of any differences for the quality of life changes was calculated as an effect size (ES). Results: The final models of hierarchical regression analysis showed that apathy measured by the Apathy evaluation scale (AES) score accounted for 59% of the variance in the Physical Health Composite Score of SF-36 and 14% of the variance in the Mental Health Composite Score of SF-36 (p<0.01). The changes in HRQoL were assessed in 52 patients with APS who completed 1-year follow-up period. The analysis of magnitude for changes in HRQoL during one-year follow-up period have shown sustained medium ES (0.50-0.79) for both Physical and Mental health composite scores, total quality of life as well as for the Physical Health, Vitality, Role Emotional and Social Functioning. Conclusion: This study provides insight into new potential predictors of HRQoL and its changes over time in patients with APS. Additionally, identification of both prognostic markers of a poor HRQoL and magnitude of its changes should be considered when developing comprehensive treatment-related strategies and health care programs aimed at improving HRQoL and well-being in patients with APS.Keywords: atypical parkinsonian syndromes, follow-up study, quality of life, APS
Procedia PDF Downloads 30571 Diagnostic Performance of Mean Platelet Volume in the Diagnosis of Acute Myocardial Infarction: A Meta-Analysis
Authors: Kathrina Aseanne Acapulco-Gomez, Shayne Julieane Morales, Tzar Francis Verame
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Mean platelet volume (MPV) is the most accurate measure of the size of platelets and is routinely measured by most automated hematological analyzers. Several studies have shown associations between MPV and cardiovascular risks and outcomes. Although its measurement may provide useful data, MPV remains to be a diagnostic tool that is yet to be included in routine clinical decision making. The aim of this systematic review and meta-analysis is to determine summary estimates of the diagnostic accuracy of mean platelet volume for the diagnosis of myocardial infarction among adult patients with angina and/or its equivalents in terms of sensitivity, specificity, diagnostic odds ratio, and likelihood ratios, and to determine the difference of the mean MPV values between those with MI and those in the non-MI controls. The primary search was done through search in electronic databases PubMed, Cochrane Review CENTRAL, HERDIN (Health Research and Development Information Network), Google Scholar, Philippine Journal of Pathology, and Philippine College of Physicians Philippine Journal of Internal Medicine. The reference list of original reports was also searched. Cross-sectional, cohort, and case-control articles studying the diagnostic performance of mean platelet volume in the diagnosis of acute myocardial infarction in adult patients were included in the study. Studies were included if: (1) CBC was taken upon presentation to the ER or upon admission (within 24 hours of symptom onset); (2) myocardial infarction was diagnosed with serum markers, ECG, or according to accepted guidelines by the Cardiology societies (American Heart Association (AHA), American College of Cardiology (ACC), European Society of Cardiology (ESC); and, (3) if outcomes were measured as significant difference AND/OR sensitivity and specificity. The authors independently screened for inclusion of all the identified potential studies as a result of the search. Eligible studies were appraised using well-defined criteria. Any disagreement between the reviewers was resolved through discussion and consensus. The overall mean MPV value of those with MI (9.702 fl; 95% CI 9.07 – 10.33) was higher than in those of the non-MI control group (8.85 fl; 95% CI 8.23 – 9.46). Interpretation of the calculated t-value of 2.0827 showed that there was a significant difference in the mean MPV values of those with MI and those of the non-MI controls. The summary sensitivity (Se) and specificity (Sp) for MPV were 0.66 (95% CI; 0.59 - 0.73) and 0.60 (95% CI; 0.43 – 0.75), respectively. The pooled diagnostic odds ratio (DOR) was 2.92 (95% CI; 1.90 – 4.50). The positive likelihood ratio of MPV in the diagnosis of myocardial infarction was 1.65 (95% CI; 1.20 – 22.27), and the negative likelihood ratio was 0.56 (95% CI; 0.50 – 0.64). The intended role for MPV in the diagnostic pathway of myocardial infarction would perhaps be best as a triage tool. With a DOR of 2.92, MPV values can discriminate between those who have MI and those without. For a patient with angina presenting with elevated MPV values, it is 1.65 times more likely that he has MI. Thus, it is implied that the decision to treat a patient with angina or its equivalents as a case of MI could be supported by an elevated MPV value.Keywords: mean platelet volume, MPV, myocardial infarction, angina, chest pain
Procedia PDF Downloads 8770 On the Development of Evidential Contrasts in the Greater Himalayan Region
Authors: Marius Zemp
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Evidentials indicate how the speaker obtained the information conveyed in a statement. Detailed diachronic-functional accounts of evidential contrasts found in the Greater Himalayan Region (GHR) reveal that contrasting evidentials are not only defined against each other but also that most of them once had different aspecto-temporal (TA) values which must have aligned when their contrast was conventionalized. Based on these accounts, the present paper sheds light on hitherto unidentified mechanisms of grammatical change. The main insights of the present study were facilitated by ‘functional reconstruction’, which (i) revolves around morphemes which appear to be used in divergent ways within a language and/or across different related languages, (ii) persistently devises hypotheses as to how these functional divergences may have developed, and (iii) retains those hypotheses which most plausibly and economically account for the data. Based on the dense and detailed grammatical literature on the Tibetic language family, the author of this study is able to reconstruct the initial steps by which its evidentiality systems developed: By the time Proto-Tibetan started to be spread across much of Central Asia in the 7th century CE, verbal concatenations with and without a connective -s had become common. As typical for resultative constructions around the globe, Proto-Tibetan *V-s-’dug ‘was there, having undergone V’ (employing the simple past of ’dug ‘stay, be there’) allowed both for a perfect reading (‘the state resulting from V holds at the moment of speech’) and an inferential reading (‘(I infer from its result that) V has taken place’). In Western Tibetic, *V-s-’dug grammaticalized in its perfect meaning as it became contrasted with perfect *V-s-yod ‘is there, having undergone V’ (employing the existential copula yod); that is, *V-s-’dug came to mean that the speaker directly witnessed the profiled result of V, whereas *V-s-yod came to mean that the speaker does not depend on direct evidence of the result, as s/he simply knows that it holds. In Eastern Tibetic, on the other hand, V-s-’dug grammaticalized in its inferential past meaning as it became contrasted with past *V-thal ‘went past V-ing’ (employing the simple past of thal ‘go past’); that is, *V-s-’dug came to mean that the profiled past event was inferred from its result, while *V-thal came to mean that it was directly witnessed. Hence, depending on whether it became contrasted with a perfect or a past construction, resultative V-s-’dug grammaticalized either its direct evidential perfect or its inferential past function. This means that in both cases, evidential readings of constructions with distinct but overlapping TA-values became contrasted, and in order for their contrasting meanings to grammaticalize, the constructions had to agree on their tertium comparationis, which was their shared TA-value. By showing that other types of evidential contrasts in the GHR are also TA-aligned, while no single markers (or privative contrasts) are found to have grammaticalized evidential functions, the present study suggests that, at least in this region of the world, evidential meanings grammaticalize only in equipollent contrasts, which always end up TA-aligned.Keywords: evidential contrasts, functional-diachronic accounts, grammatical change, himalayan languages, tense/aspect-alignment
Procedia PDF Downloads 12869 Anti-DNA Antibodies from Patients with Schizophrenia Hydrolyze DNA
Authors: Evgeny A. Ermakov, Lyudmila P. Smirnova, Valentina N. Buneva
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Schizophrenia associated with dysregulation of neurotransmitter processes in the central nervous system and disturbances in the humoral immune system resulting in the formation of antibodies (Abs) to the various components of the nervous tissue. Abs to different neuronal receptors and DNA were detected in the blood of patients with schizophrenia. Abs hydrolyzing DNA were detected in pool of polyclonal autoantibodies in autoimmune and infectious diseases, such catalytic Abs were named abzymes. It is believed that DNA-hydrolyzing abzymes are cytotoxic, cause nuclear DNA fragmentation and induce cell death by apoptosis. Abzymes with DNAase activity are interesting because of the mechanism of formation and the possibility of use as diagnostic markers. Therefore, in our work we have set following goals: to determine the level anti-DNA Abs in the serum of patients with schizophrenia and to study DNA-hydrolyzing activity of IgG of patients with schizophrenia. Materials and methods: In our study there were included 41 patients with a verified diagnosis of paranoid or simple schizophrenia and 24 healthy donors. Electrophoretically and immunologically homogeneous IgGs were obtained by sequential affinity chromatography of the serum proteins on protein G-Sepharose and gel filtration. The levels of anti-DNA Abs were determined using ELISA. DNA-hydrolyzing activity was detected as the level of supercoiled pBluescript DNA transition in circular and linear forms, the hydrolysis products were analyzed by agarose electrophoresis followed by ethidium bromide stain. To correspond the registered catalytic activity directly to the antibodies we carried out a number of strict criteria: electrophoretic homogeneity of the antibodies, gel filtration (acid shock analysis) and in situ activity. Statistical analysis was performed in ‘Statistica 9.0’ using the non-parametric Mann-Whitney test. Results: The sera of approximately 30% of schizophrenia patients displayed a higher level of Abs interacting with single-stranded (ssDNA) and double-stranded DNA (dsDNA) compared with healthy donors. The average level of Abs interacting with ssDNA was only 1.1-fold lower than that for interacting with dsDNA. IgG of patient with schizophrenia were shown to possess DNA hydrolyzing activity. Using affinity chromatography, electrophoretic analysis of isolated IgG homogeneity, gel filtration in acid shock conditions and in situ DNAse activity analysis we proved that the observed activity is intrinsic property of studied antibodies. We have shown that the relative DNAase activity of IgG in patients with schizophrenia averaged 55.4±32.5%, IgG of healthy donors showed much lower activity (average of 9.1±6.5%). It should be noted that DNAase activity of IgG in patients with schizophrenia with a negative symptoms was significantly higher (73.3±23.8%), than in patients with positive symptoms (43.3±33.1%). Conclusion: Anti-DNA Abs of patients with schizophrenia not only bind DNA, but quite efficiently hydrolyze the substrate. The data show a correlation with the level of DNase activity and leading symptoms of patients with schizophrenia.Keywords: anti-DNA antibodies, abzymes, DNA hydrolysis, schizophrenia
Procedia PDF Downloads 32868 The Solid-Phase Sensor Systems for Fluorescent and SERS-Recognition of Neurotransmitters for Their Visualization and Determination in Biomaterials
Authors: Irina Veselova, Maria Makedonskaya, Olga Eremina, Alexandr Sidorov, Eugene Goodilin, Tatyana Shekhovtsova
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Such catecholamines as dopamine, norepinephrine, and epinephrine are the principal neurotransmitters in the sympathetic nervous system. Catecholamines and their metabolites are considered to be important markers of socially significant diseases such as atherosclerosis, diabetes, coronary heart disease, carcinogenesis, Alzheimer's and Parkinson's diseases. Currently, neurotransmitters can be studied via electrochemical and chromatographic techniques that allow their characterizing and quantification, although these techniques can only provide crude spatial information. Besides, the difficulty of catecholamine determination in biological materials is associated with their low normal concentrations (~ 1 nM) in biomaterials, which may become even one more order lower because of some disorders. In addition, in blood they are rapidly oxidized by monoaminooxidases from thrombocytes and, for this reason, the determination of neurotransmitter metabolism indicators in an organism should be very rapid (15—30 min), especially in critical states. Unfortunately, modern instrumental analysis does not offer a complex solution of this problem: despite its high sensitivity and selectivity, HPLC-MS cannot provide sufficiently rapid analysis, while enzymatic biosensors and immunoassays for the determination of the considered analytes lack sufficient sensitivity and reproducibility. Fluorescent and SERS-sensors remain a compelling technology for approaching the general problem of selective neurotransmitter detection. In recent years, a number of catecholamine sensors have been reported including RNA aptamers, fluorescent ribonucleopeptide (RNP) complexes, and boronic acid based synthetic receptors and the sensor operated in a turn-off mode. In this work we present the fluorescent and SERS turn-on sensor systems based on the bio- or chemorecognizing nanostructured films {chitosan/collagen-Tb/Eu/Cu-nanoparticles-indicator reagents} that provide the selective recognition, visualization, and sensing of the above mentioned catecholamines on the level of nanomolar concentrations in biomaterials (cell cultures, tissue etc.). We have (1) developed optically transparent porous films and gels of chitosan/collagen; (2) ensured functionalization of the surface by molecules-'recognizers' (by impregnation and immobilization of components of the indicator systems: biorecognizing and auxiliary reagents); (3) performed computer simulation for theoretical prediction and interpretation of some properties of the developed materials and obtained analytical signals in biomaterials. We are grateful for the financial support of this research from Russian Foundation for Basic Research (grants no. 15-03-05064 a, and 15-29-01330 ofi_m).Keywords: biomaterials, fluorescent and SERS-recognition, neurotransmitters, solid-phase turn-on sensor system
Procedia PDF Downloads 40667 Effect of 12 Weeks Pedometer-Based Workplace Program on Inflammation and Arterial Stiffness in Young Men with Cardiovascular Risks
Authors: Norsuhana Omar, Amilia Aminuddina Zaiton Zakaria, Raifana Rosa Mohamad Sattar, Kalaivani Chellappan, Mohd Alauddin Mohd Ali, Norizam Salamt, Zanariyah Asmawi, Norliza Saari, Aini Farzana Zulkefli, Nor Anita Megat Mohd. Nordin
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Inflammation plays an important role in the pathogenesis of vascular dysfunction leading to arterial stiffness. Pulse wave velocity (PWV) and augmentation index (AS), as tools for the assessment of vascular damages are widely used and have been shown to predict cardiovascular disease (CVD). C-reactive protein (CRP) is a marker of inflammation. Several studies noted that regular exercise is associated with reduced arterial stiffness. The lack of exercise among Malaysians and the increasing CVD morbidity and mortality among young men are of concern. In Malaysia data on the workplace exercise intervention is scarce. A programme was designed to enable subjects to increase their level of walking as part of their daily work routine and self-monitored by using pedometers. The aim of this study to evaluate the reducing of inflammation by measuring CRP and improvement arterial stiffness measured by carotid femoral PWV (PWVCF) and AI. A total of 70 young men (20 - 40 years) who were sedentary, achieving less than 5,000 steps/day in casual walking with 2 or more cardiovascular risk factors were recruited in Institute of Vocational Skills for Youth (IKBN Hulu Langat). Subjects were randomly assigned to a control (CG) (n=34; no change in walking) and pedometer group (PG) (n=36; minimum target: 8,000 steps/day). The CRP was measured by using immunological method while PWVCF and AI were measured using Vicorder. All parameters were measured at baseline and after 12 weeks. Data for analysis was conducted using Statistical Package of Social Sciences Version 22 (SPSS Inc., Chicago, IL, USA). At post intervention, the CG step counts were similar (4983 ± 366vs 5697 ± 407steps/day). The PG increased step count from 4996 ± 805 to 10,128 ±511 steps/day (P<0.001). The PG showed significant improvement in anthropometric variables and lipid (time and group effect p<0.001). For vascular assessment, the PG showed significantly decreased for time and effect (p<0.001) for PWV (7.21± 0.83 to 6.42 ± 0.89) m/s; AI (11.88± 6.25 to 8.83 ± 3.7) % and CRP (pre= 2.28 ± 3.09, post=1.08± 1.37mg/L). However, no changes were seen in CG. As a conclusion, a pedometer-based walking programme may be an effective strategy for promoting increased daily physical activity which reduces cardiovascular risk markers and thus improve cardiovascular health in terms of inflammation and arterial stiffness. The community intervention for health maintenance has potential to adopt walking as an exercise and adopting vascular fitness index as the performance measuring tools.Keywords: arterial stiffness, exercise, inflammation, pedometer
Procedia PDF Downloads 35466 DeepNIC a Method to Transform Each Tabular Variable into an Independant Image Analyzable by Basic CNNs
Authors: Nguyen J. M., Lucas G., Ruan S., Digonnet H., Antonioli D.
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Introduction: Deep Learning (DL) is a very powerful tool for analyzing image data. But for tabular data, it cannot compete with machine learning methods like XGBoost. The research question becomes: can tabular data be transformed into images that can be analyzed by simple CNNs (Convolutional Neuron Networks)? Will DL be the absolute tool for data classification? All current solutions consist in repositioning the variables in a 2x2 matrix using their correlation proximity. In doing so, it obtains an image whose pixels are the variables. We implement a technology, DeepNIC, that offers the possibility of obtaining an image for each variable, which can be analyzed by simple CNNs. Material and method: The 'ROP' (Regression OPtimized) model is a binary and atypical decision tree whose nodes are managed by a new artificial neuron, the Neurop. By positioning an artificial neuron in each node of the decision trees, it is possible to make an adjustment on a theoretically infinite number of variables at each node. From this new decision tree whose nodes are artificial neurons, we created the concept of a 'Random Forest of Perfect Trees' (RFPT), which disobeys Breiman's concepts by assembling very large numbers of small trees with no classification errors. From the results of the RFPT, we developed a family of 10 statistical information criteria, Nguyen Information Criterion (NICs), which evaluates in 3 dimensions the predictive quality of a variable: Performance, Complexity and Multiplicity of solution. A NIC is a probability that can be transformed into a grey level. The value of a NIC depends essentially on 2 super parameters used in Neurops. By varying these 2 super parameters, we obtain a 2x2 matrix of probabilities for each NIC. We can combine these 10 NICs with the functions AND, OR, and XOR. The total number of combinations is greater than 100,000. In total, we obtain for each variable an image of at least 1166x1167 pixels. The intensity of the pixels is proportional to the probability of the associated NIC. The color depends on the associated NIC. This image actually contains considerable information about the ability of the variable to make the prediction of Y, depending on the presence or absence of other variables. A basic CNNs model was trained for supervised classification. Results: The first results are impressive. Using the GSE22513 public data (Omic data set of markers of Taxane Sensitivity in Breast Cancer), DEEPNic outperformed other statistical methods, including XGBoost. We still need to generalize the comparison on several databases. Conclusion: The ability to transform any tabular variable into an image offers the possibility of merging image and tabular information in the same format. This opens up great perspectives in the analysis of metadata.Keywords: tabular data, CNNs, NICs, DeepNICs, random forest of perfect trees, classification
Procedia PDF Downloads 12565 Effect of Nigella Sativa Seeds and Ajwa Date on Blood Glucose Level in Saudi Patients with Type 2 Diabetes Mellitus
Authors: Reham Algheshairy, Khaled Tayeb, Christopher Smith, Rebecca Gregg, Haruna Musa
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Background: Diabetes is a medical condition that refers to the pancreas’ inability to secrete sufficient insulin levels, a hormone responsible for controlling glucose levels in the body. Any surplus glucose in the blood stream is excreted through the urinary system. Insulin resistance in blood cells can also cause this condition despite the fact that the pancreas is producing the required amount of insulin A number of researchers claim that the prevalence of diabetes in Saudi Arabia has reached epidemic proportions, although one study did observe one positive in the rise in the awareness of diabetes, possibly indicative of Saudi Arabia’s improving healthcare system. While a number of factors can cause diabetes, the ever-increasing incidence of the disease in Saudi Arabia has been blamed primarily on low levels of physical activity and high levels of obesity. Objectives: The project has two aims. The first aim of the project is to investigate the regulatory effects of consumption of Nigella seeds and Ajwah dates on blood glucose levels in diabetic patients with type 2 diabetes. The second aim of the project is to investigate whether these dietary factors may have potentially beneficial effects in controlling the complications that associated with type 2 diabetes. Methods: This use a random-cross intervention trail of 75 Saudi male and female with type 2 diabetes in Al-Noor hospital in Makkah ( KSA) aged between 18 and 70 years were divided into 3 groups. Group 1 will consume 2g of Nigella Sativa seeds daily along with a modified diet for 12 weeks, group 2 will be given Ajwah dates daily with a modified diet for 12 weeks and group 3 will follow a modified diet for 12 weeks. Anthropometric measurements were taken at baseline, along with bloods for HbA1c, fasting blood sugar and at the end of 12 weeks. Results: This study found significant decrease in blood level (FBG & 2PPBG) and HbA1c in the groups with diet and Nigella seeds) compared to Ajwa date. However, there is no significant change were found in HbA1c, FBG and 2hrpp regarding Ajwa group. Conclusion: This study illustrated a significant improvement in some markers of glycaemia following 2 g of Ns and diet for 12 weeks. The dose of 2g/day of consumed Nigella seeds was found to be more effective in controlling BGL and HbA1c than control and Ajwa groups. This suggests that Nigella seeds and following a diet may have a potential effect (a role in controlling outcomes for type 2 diabetes and controlling the disease). Further research is needed on a large scale to determine the optimum dose and duration of Nigella and Ajwa in order to achieve the desired results.Keywords: type 2 diabetes, Nigella seeds, Ajwa dates, fasting blood glucose, control
Procedia PDF Downloads 29564 Inpatient Glycemic Management Strategies and Their Association with Clinical Outcomes in Hospitalized SARS-CoV-2 Patients
Authors: Thao Nguyen, Maximiliano Hyon, Sany Rajagukguk, Anna Melkonyan
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Introduction: Type 2 Diabetes is a well-established risk factor for severe SARS-CoV-2 infection. Uncontrolled hyperglycemia in patients with established or newly diagnosed diabetes is associated with poor outcomes, including increased mortality and hospital length of stay. Objectives: Our study aims to compare three different glycemic management strategies and their association with clinical outcomes in patients hospitalized for moderate to severe SARS-CoV-2 infection. Identifying optimal glycemic management strategies will improve the quality of patient care and improve their outcomes. Method: This is a retrospective observational study on patients hospitalized at Adventist Health White Memorial with severe SARS-CoV-2 infection from 11/1/2020 to 02/28/2021. The following inclusion criteria were used: positive SARS-CoV-2 PCR test, age >18 yrs old, diabetes or random glucose >200 mg/dL on admission, oxygen requirement >4L/min, and treatment with glucocorticoids. Our exclusion criteria included: ICU admission within 24 hours, discharge within five days, death within five days, and pregnancy. The patients were divided into three glycemic management groups: Group 1, managed solely by the Primary Team, Group 2, by Pharmacy; and Group 3, by Endocrinologist. Primary outcomes were average glucose on Day 5, change in glucose between Days 3 and 5, and average insulin dose on Day 5 among groups. Secondary outcomes would be upgraded to ICU, inpatient mortality, and hospital length of stay. For statistics, we used IBM® SPSS, version 28, 2022. Results: Most studied patients were Hispanic, older than 60, and obese (BMI >30). It was the first CV-19 surge with the Delta variant in an unvaccinated population. Mortality was markedly high (> 40%) with longer LOS (> 13 days) and a high ICU transfer rate (18%). Most patients had markedly elevated inflammatory markers (CRP, Ferritin, and D-Dimer). These, in combination with glucocorticoids, resulted in severe hyperglycemia that was difficult to control. Average glucose on Day 5 was not significantly different between groups primary vs. pharmacy vs. endocrine (220.5 ± 63.4 vs. 240.9 ± 71.1 vs. 208.6 ± 61.7 ; P = 0.105). Change in glucose from days 3 to 5 was not significantly different between groups but trended towards favoring the endocrinologist group (-26.6±73.6 vs. 3.8±69.5 vs. -32.2±84.1; P= 0.052). TDD insulin was not significantly different between groups but trended towards higher TDD for the endocrinologist group (34.6 ± 26.1 vs. 35.2 ± 26.4 vs. 50.5 ± 50.9; P=0.054). The endocrinologist group used significantly more preprandial insulin compared to other groups (91.7% vs. 39.1% vs. 65.9% ; P < 0.001). The pharmacy used more basal insulin than other groups (95.1% vs. 79.5% vs. 79.2; P = 0.047). There were no differences among groups in the clinical outcomes: LOS, ICU upgrade, or mortality. Multivariate regression analysis controlled for age, sex, BMI, HbA1c level, renal function, liver function, CRP, d-dimer, and ferritin showed no difference in outcomes among groups. Conclusion: Given high-risk factors in our population, despite efforts from the glycemic management teams, it’s unsurprising no differences in clinical outcomes in mortality and length of stay.Keywords: glycemic management, strategies, hospitalized, SARS-CoV-2, outcomes
Procedia PDF Downloads 44863 Identifying Biomarker Response Patterns to Vitamin D Supplementation in Type 2 Diabetes Using K-means Clustering: A Meta-Analytic Approach to Glycemic and Lipid Profile Modulation
Authors: Oluwafunmibi Omotayo Fasanya, Augustine Kena Adjei
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Background and Aims: This meta-analysis aimed to evaluate the effect of vitamin D supplementation on key metabolic and cardiovascular parameters, such as glycated hemoglobin (HbA1C), fasting blood sugar (FBS), low-density lipoprotein (LDL), high-density lipoprotein (HDL), systolic blood pressure (SBP), and total vitamin D levels in patients with Type 2 diabetes mellitus (T2DM). Methods: A systematic search was performed across databases, including PubMed, Scopus, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov, from January 1990 to January 2024. A total of 4,177 relevant studies were initially identified. Using an unsupervised K-means clustering algorithm, publications were grouped based on common text features. Maximum entropy classification was then applied to filter studies that matched a pre-identified training set of 139 potentially relevant articles. These selected studies were manually screened for relevance. A parallel manual selection of all initially searched studies was conducted for validation. The final inclusion of studies was based on full-text evaluation, quality assessment, and meta-regression models using random effects. Sensitivity analysis and publication bias assessments were also performed to ensure robustness. Results: The unsupervised K-means clustering algorithm grouped the patients based on their responses to vitamin D supplementation, using key biomarkers such as HbA1C, FBS, LDL, HDL, SBP, and total vitamin D levels. Two primary clusters emerged: one representing patients who experienced significant improvements in these markers and another showing minimal or no change. Patients in the cluster associated with significant improvement exhibited lower HbA1C, FBS, and LDL levels after vitamin D supplementation, while HDL and total vitamin D levels increased. The analysis showed that vitamin D supplementation was particularly effective in reducing HbA1C, FBS, and LDL within this cluster. Furthermore, BMI, weight gain, and disease duration were identified as factors that influenced cluster assignment, with patients having lower BMI and shorter disease duration being more likely to belong to the improvement cluster. Conclusion: The findings of this machine learning-assisted meta-analysis confirm that vitamin D supplementation can significantly improve glycemic control and reduce the risk of cardiovascular complications in T2DM patients. The use of automated screening techniques streamlined the process, ensuring the comprehensive evaluation of a large body of evidence while maintaining the validity of traditional manual review processes.Keywords: HbA1C, T2DM, SBP, FBS
Procedia PDF Downloads 1262 Implementation of Active Recovery at Immediate, 12 and 24 Hours Post-Training in Young Soccer Players
Authors: C. Villamizar, M. Serrato
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In the pursuit of athletic performance, the role of physical training which is determined by a number of charges or taxes on physiological stress and musculoskeletal systems of the human body generated by the intensity and duration is fundamental. Given the physical demands of these activities both training and competitive must take into account the optimal relationship with a straining process recovery post favoring the process of overcompensation which aims to facilitate the return and rising energy potential and protein synthesis also of different tissues. Allowing muscle function returns to baseline or pre-exercise states. If this recovery process is not performed or is not allowed in a proper way, will result in an increased state of fatigue. Active recovery, is one of the strategies implemented in the sport for a return to pre-exercise physiological states. However, there are some adverse assumptions regarding the negative effects, as is the possibility of increasing the degradation of muscle glycogen and thus delaying the synthesis thereof. For them, it is necessary to investigate what would be the effects generated application made at different times after the effort. The aim of this study was to determine the effects of active recovery post effort made at three different times: immediately, at 12 and 24 hours on biochemical markers creatine kinase in youth soccer player’s categories. A randomized controlled trial with allocation to three groups was performed: A. active recovery immediately after the effort; B. active recovery performed at 12 hours after the effort; C. active recovery made at 24 hours after the effort. This study included 27 subjects belonging to a Colombian soccer team of the second division. Vital signs, weight, height, BMI, the percentage of muscle mass, fat mass percentage, personal medical history, and family were valued. The velocity, explosive force and Creatin Kinase (CK) in blood were tested before and after interventions. SAFT 90 protocol (Soccer Field specific Aerobic Test) was applied to participants for generating fatigue. CK samples were taken one hour before the application of the fatigue test, one hour after the fatigue protocol and 48 of the initial CK sample. Mean age was 18.5 ± 1.1 years old. Improvements in jumping and speed recovery the 3 groups (p < 0.05), but no statistically significant differences between groups was observed after recuperation. In all participants, there was a significant increment of CK when applied SAFT 90 in all the groups (median 103.1-111.1). The CK measurement after 48 hours reflects a recovery in all groups, however the group C, a decline below baseline levels of -55.5 (-96.3 /-20.4) which is a significant find. Other research has shown that CK does not return quickly to their baseline, but our study shows that active recovery favors the clearance of CK and also to perform recovery 24 hours after the effort generates higher clearance of this biomarker.Keywords: active recuperation, creatine phosphokinase, post training, young soccer players
Procedia PDF Downloads 16061 Genetic Diversity of Termite (Isoptera) Fauna of Western Ghats of India
Authors: A. S. Vidyashree, C. M. Kalleshwaraswamy, R. Asokan, H. M. Mahadevaswamy
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Termites are very vital ecological thespians in tropical ecosystem, having been designated as “ecosystem engineers”, due to their significant role in providing soil ecosystem services. Despite their importance, our understanding of a number of their basic biological processes in termites is extremely limited. Developing a better understanding of termite biology is closely dependent upon consistent species identification. At present, identification of termites is relied on soldier castes. But for many species, soldier caste is not reported, that creates confusion in identification. The use of molecular markers may be helpful in estimating phylogenetic relatedness between the termite species and estimating genetic differentiation among local populations within each species. To understand this, termites samples were collected from various places of Western Ghats covering four states namely Karnataka, Kerala, Tamil Nadu, Maharashtra during 2013-15. Termite samples were identified based on their morphological characteristics, molecular characteristics, or both. Survey on the termite fauna in Karnataka, Kerala, Maharashtra and Tamil Nadu indicated the presence of a 16 species belongs to 4 subfamilies under two families viz., Rhinotermitidae and Termitidae. Termititidae was the dominant family which was belonging to 4 genera and four subfamilies viz., Macrotermitinae, Amitermitinae, Nasutitermitinae and Termitinae. Amitermitinae had three species namely, Microcerotermes fletcheri, M. pakistanicus and Speculitermes sinhalensis. Macrotermitinae had the highest number of species belonging two genera, namely Microtermes and Odontotermes. Microtermes genus was with only one species i.e., Microtermes obesi. The genus Odontotermes was represented by the highest number of species (07), namely, O. obesus was the dominant (41 per cent) and the most widely distributed species in Karnataka, Karala, Maharashtra and Tamil nadu followed by O. feae (19 per cent), O.assmuthi (11 per cent) and others like O. bellahunisensis O. horni O. redemanni, O. yadevi. Nasutitermitinae was represented by two genera namely Nasutitermes anamalaiensis and Trinervitermes biformis. Termitinae subfamily was represented by Labiocapritermes distortus. Rhinotermitidae was represented by single subfamily Heterotermetinae. In Heterotermetinae, two species namely Heterotermes balwanthi and H. malabaricus were recorded. Genetic relationship among termites collected from various locations of Western Ghats of India was characterized based on mitochondrial DNA sequences (12S, 16S, and COII). Sequence analysis and divergence among the species was assessed. These results suggest that the use of both molecular and morphological approaches is crucial in ensuring accurate species identification. Efforts were made to understand their evolution and to address the ambiguities in morphological taxonomy. The implication of the study in revising the taxonomy of Indian termites, their characterization and molecular comparisons between the sequences are discussed.Keywords: isoptera, mitochondrial DNA sequences, rhinotermitidae, termitidae, Western ghats
Procedia PDF Downloads 26660 Magnetic SF (Silk Fibroin) E-Gel Scaffolds Containing bFGF-Conjugated Fe3O4 Nanoparticles
Authors: Z. Karahaliloğlu, E. Yalçın, M. Demirbilek, E.B. Denkbaş
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Critical-sized bone defects caused by trauma, bone diseases, prosthetic implant revision or tumor excision cannot be repaired by physiological regenerative processes. Current orthopedic applications for critical-sized bone defects are to use autologous bone grafts, bone allografts, or synthetic graft materials. However, these strategies are unable to solve completely the problem, and motivate the development of novel effective biological scaffolds for tissue engineering applications and regenerative medicine applications. In particular, scaffolds combined with a variety of bio-agents as fundamental tools emerge to provide the regeneration of damaged bone tissues due to their ability to promote cell growth and function. In this study, a magnetic silk fibroin (SF) hydrogel scaffold was prepared by electrogelation process of the concentrated Bombxy mori silk fibroin (8 %wt) aqueous solution. For enhancement of osteoblast-like cells (SaOS-2) growth and adhesion, basal fibroblast growth factor (bFGF) were conjugated physically to the HSA-coated magnetic nanoparticles (Fe3O4) and magnetic SF e-gel scaffolds were prepared by incorporation of Fe3O4, HSA (human serum albumin)=Fe3O4 and HSA=Fe3O4-bFGF nanoparticles. HSA=Fe3O4, HSA=Fe3O4-bFGF loaded and bare SF e-gels scaffolds were characterized using scanning electron microscopy (SEM.) For cell studies, human osteoblast-like cell line (SaOS-2) was used and an MTT assay was used to assess the cytotoxicity of magnetic silk fibroin e-gel scaffolds and cell density on these surfaces. For the evaluation osteogenic activation, ALP (alkaline phosphatase), the amount of mineralized calcium, total protein and collagen were studied. Fe3O4 nanoparticles were successfully synthesized and bFGF was conjugated to HSA=Fe3O4 nanoparticles with %97.5 of binding yield which has a particle size of 71.52±2.3 nm. Electron microscopy images of the prepared HSA and bFGF incorporated SF e-gel scaffolds showed a 3D porous morphology. In terms of water uptake results, bFGF conjugated HSA=Fe3O4 nanoparticles has the best water absorbability behavior among all groups. In the in-vitro cell culture studies realized using SaOS-2 cell line, the coating of Fe3O4 nanoparticles surface with a protein enhance the cell viability and HSA coating and bFGF conjugation, the both have an inductive effect in the cell proliferation. One of the markers of bone formation and osteoblast differentiation, according to the ALP activity and total protein results, HSA=Fe3O4-bFGF loaded SF e-gels had significantly enhanced ALP activity. Osteoblast cultured HSA=Fe3O4-bFGF loaded SF e-gels deposited more calcium compared with SF e-gel. The proposed magnetic scaffolds seem to be promising for bone tissue regeneration and used in future work for various applications.Keywords: basic fibroblast growth factor (bFGF), e-gel, iron oxide nanoparticles, silk fibroin
Procedia PDF Downloads 28959 Biocompatibility assessment of different origin Barrier Membranes for Guided Bone Regeneration
Authors: Antonio Munar-Frau, Sascha Klismoch, Manfred Schmolz, Federico Hernandez-Alfaro, Jordi Caballe-Serrano
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Introduction: Biocompatibility of biomaterials has been proposed as one of the main criteria for treatment success. For guided bone regeneration (GBR), barrier membranes present a conflict given the number of origins and modifications of these materials. The biologic response to biomaterials is orchestrated by a series of events leading to the integration or rejection of the biomaterial, posing questions such as if a longer occlusive property may trigger an inflammatory reaction. Whole blood cultures are a solution to study the immune response to drugs or biomaterials during the first 24-48 hours. The aim of this study is to determine the early immune response of different origins and chemical modifications of barrier membranes. Materials & Methods: 5 different widely used barrier membranes were included in this study: Acellular dermal matrix (AlloDerm, LifeCell®), Porcine Peritoneum (BioGide, Geistlich Pharma®), Porcine Pericardium (Jason, Botiss Biomaterials GmbH®), Porcine Cross-linked collagen (Ossix Plus, Datum Dental®) and d-PTFE (Cytoplast TXT, Osteogenics Biomedical®). Blood samples were extracted from 3 different healthy donors and incubated with the different samples of barrier membranes for 24 hours. After the incubation time, serum samples were obtained and analyzed by means of biocompatibility assays taking into account 42 markers. Results: In an early stage of the inflammatory response, the Acellular dermal matrix, porcine peritoneum and porcine cross-linked collagen expressed similar patterns of cytokine expression with a great manifestation of ENA 78. Porcine pericardium and d-PTFE presented similar cytokine activation, especially for MMP-3 and MMP-9, although other cytokines were highlighted with lower expression. For the later immune response, Porcine peritoneum and acellular dermal matrix MCP-1 and IL-15 were evident. Porcine pericardium, porcine cross-linked collagen and d-PTFE presented a high expression of IL-16 and lower manifestation of other cytokines. Different behaviors depending on an earlier or later stage of the inflammation process were observed. Barrier membrane inflammatory expression does not only differ depending on the origin, variables such as treatment of the collagen and polymers may also have a great impact on the cytokine expression of the studied barrier membranes during inflammation. Conclusions: Surface treatment and modifications might affect the biocompatibility of the membranes, as different cytokine expressions were evidently depending on the origin of the biomaterial. This study is only a brushstroke regarding the biocompatibility of materials, as it is one of the pioneer studies for ex vivo barrier membranes assays. Studies regarding surface modification are needed in order to clarify mystifications of barrier membrane science.Keywords: biomaterials, bone regeneration, biocompatibility, inflammation
Procedia PDF Downloads 16058 Growth and Differentiation of Mesenchymal Stem Cells on Titanium Alloy Ti6Al4V and Novel Beta Titanium Alloy Ti36Nb6Ta
Authors: Eva Filová, Jana Daňková, Věra Sovková, Matej Daniel
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Titanium alloys are biocompatible metals that are widely used in clinical practice as load bearing implants. The chemical modification may influence cell adhesion, proliferation, and differentiation as well as stiffness of the material. The aim of the study was to evaluate the adhesion, growth and differentiation of pig mesenchymal stem cells on the novel beta titanium alloy Ti36Nb6Ta compared to standard medical titanium alloy Ti6Al4V. Discs of Ti36Nb6Ta and Ti6Al4V alloy were sterilized by ethanol, put in 48-well plates, and seeded by pig mesenchymal stem cells at the density of 60×103/cm2 and cultured in Minimum essential medium (Sigma) supplemented with 10% fetal bovine serum and penicillin/streptomycin. Cell viability was evaluated using MTS assay (CellTiter 96® AQueous One Solution Cell Proliferation Assay;Promega), cell proliferation using Quant-iT™ ds DNA Assay Kit (Life Technologies). Cells were stained immunohistochemically using monoclonal antibody beta-actin, and secondary antibody conjugated with AlexaFluor®488 and subsequently the spread area of cells was measured. Cell differentiation was evaluated by alkaline phosphatase assay using p-nitrophenyl phosphate (pNPP) as a substrate; the reaction was stopped by NaOH, and the absorbance was measured at 405 nm. Osteocalcin, specific bone marker was stained immunohistochemically and subsequently visualized using confocal microscopy; the fluorescence intensity was analyzed and quantified. Moreover, gene expression of osteogenic markers osteocalcin and type I collagen was evaluated by real-time reverse transcription-PCR (qRT-PCR). For statistical evaluation, One-way ANOVA followed by Student-Newman-Keuls Method was used. For qRT-PCR, the nonparametric Kruskal-Wallis Test and Dunn's Multiple Comparison Test were used. The absorbance in MTS assay was significantly higher on titanium alloy Ti6Al4V compared to beta titanium alloy Ti36Nb6Ta on days 7 and 14. Mesenchymal stem cells were well spread on both alloys, but no difference in spread area was found. No differences in alkaline phosphatase assay, fluorescence intensity of osteocalcin as well as the expression of type I collagen, and osteocalcin genes were observed. Higher expression of type I collagen compared to osteocalcin was observed for cells on both alloys. Both beta titanium alloy Ti36Nb6Ta and titanium alloy Ti6Al4V Ti36Nb6Ta supported mesenchymal stem cellsˈ adhesion, proliferation and osteogenic differentiation. Novel beta titanium alloys Ti36Nb6Ta is a promising material for bone implantation. The project was supported by the Czech Science Foundation: grant No. 16-14758S, the Grant Agency of the Charles University, grant No. 1246314 and by the Ministry of Education, Youth and Sports NPU I: LO1309.Keywords: beta titanium, cell growth, mesenchymal stem cells, titanium alloy, implant
Procedia PDF Downloads 31657 Research on Reducing Food Losses by Extending the Date of Minimum Durability on the Example of Cereal Products
Authors: Monika Trzaskowska, Dorota Zielinska, Anna Lepecka, Katarzyna Neffe-Skocinska, Beata Bilska, Marzena Tomaszewska, Danuta Kolozyn-Krajewska
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Microbiological quality and food safety are important food characteristics. Regulation (EU) No 1169/2011 of the European Parliament and of the Council on the provision of food information to consumers introduces the obligation to provide information on the 'use-by' date or the date of minimum durability (DMD). The second term is the date until which the properly stored or transported foodstuff retains its physical, chemical, microbiological and organoleptic properties. The date should be preceded by 'best before'. It is used for durable products, e.g., pasta. In relation to reducing food losses, the question may be asked whether products with the date of minimum durability currently declared retain quality and safety beyond this. The aim of the study was to assess the sensory quality and microbiological safety of selected cereal products, i.e., pasta and millet after DMD. The scope of the study was to determine the markers of microbiological quality, i.e., the total viable count (TVC), the number of bacteria from the Enterobacteriaceae family and the number of yeast and mold (TYMC) on the last day of DMD and after 1 and 3 months of storage. In addition, the presence of Salmonella and Listeria monocytogenes was examined on the last day of DMD. The sensory quality of products was assessed by quantitative descriptive analysis (QDA), the intensity of 14 differentiators and overall quality were defined and determined. In the tested samples of millet and pasta, no pathogenic bacteria Salmonella and Listeria monocytogenes were found. The value of the distinguishing features of selected quality and microbiological safety indicators on the last DMD day was in the range of about 3-1 log cfu/g. This demonstrates the good microbiological quality of the tested food. Comparing the products, a higher number of microorganisms was found in the samples of millet. After 3 months of storage, TVC decreased in millet, while in pasta, it was found to increase in value. In both products, the number of bacteria from the Enterobacretiaceae family decreased. In contrast, the number of TYMCs increased in samples of millet, and in pasta decreased. The intensity of sensory characteristic in the studied period varied. It remained at a similar level or increased. Millet was found to increase the intensity and flavor of 'cooked porridge' 3 months after DMD. Similarly, in the pasta, the smell and taste of 'cooked pasta' was more intense. To sum up, the researched products on the last day of the minimum durability date were characterized by very good microbiological and sensory quality, which was maintained for 3 months after this date. Based on these results, the date of minimum durability of tested products could be extended. The publication was financed on the basis of an agreement with the National Center for Research and Development No. Gospostrateg 1/385753/1/NCBR/2018 for the implementation and financing of the project under the strategic research and development program 'social and economic development of Poland in the conditions of globalizing markets – GOSPOSTRATEG - acronym PROM'.Keywords: date of minimum durability, food losses, food quality and safety, millet, pasta
Procedia PDF Downloads 16156 Targeting Glucocorticoid Receptor Eliminate Dormant Chemoresistant Cancer Stem Cells in Glioblastoma
Authors: Aoxue Yang, Weili Tian, Haikun Liu
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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Glucocorticoids (GCs) are used to treat GBM-associated edema. However, glucocorticoids participate in the physiological response to psychosocial stress, linked to poor cancer prognosis. This raises concern that glucocorticoids affect the tumor and BTSCs. Identifying markers specifically expressed by brain tumor stem cells (BTSCs) may enable specific therapies that spare their regular tissue-resident counterparts. By ribosome profiling analysis, we have identified that glycerol-3-phosphate dehydrogenase 1 (GPD1) is expressed by dormant BTSCs but not by NSCs. Through different stress-induced experiments in vitro, we found that only dexamethasone (DEXA) can significantly increase the expression of GPD1 in NSCs. Adversely, mifepristone (MIFE) which is classified as glucocorticoid receptors antagonists, could decrease GPD1 protein level and weaken the proliferation and stemness in BTSCs. Furthermore, DEXA can induce GPD1 expression in tumor-bearing mice brains and shorten animal survival, whereas MIFE has a distinct adverse effect that prolonged mice lifespan. Knocking out GR in NSC can block the upregulation of GPD1 inducing by DEXA, and we find the specific sequences on GPD1 promotor combined with GR, thus improving the efficiency of GPD1 transcription from CHIP-Seq. Moreover, GR and GPD1 are highly co-stained on GBM sections obtained from patients and mice. All these findings confirmed that GR could regulate GPD1 and loss of GPD1 Impairs Multiple Pathways Important for BTSCs Maintenance GPD1 is also a critical enzyme regulating glycolysis and lipid synthesis. We observed that DEXA and MIFE could change the metabolic profiles of BTSCs by regulating GPD1 to shift the transition of cell dormancy. Our transcriptome and lipidomics analysis demonstrated that cell cycle signaling and phosphoglycerides synthesis pathways contributed a lot to the inhibition of GPD1 caused by MIFE. In conclusion, our findings raise concern that treatment of GBM with GCs may compromise the efficacy of chemotherapy and contribute to BTSC dormancy. Inhibition of GR can dramatically reduce GPD1 and extend the survival duration of GBM-bearing mice. The molecular link between GPD1 and GR may give us an attractive therapeutic target for glioblastoma.Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides
Procedia PDF Downloads 13255 Colonizing the Colonizers: Layers of Subjectification in the Russian Caucasus
Authors: Aaron Derner
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Unlike the histories of France, the UK, or even Spain, the Russian colonial past often dissolves before the seemingly more salient Cold War figurations or Soviet dissolution. The obvious explanation behind Caucasian states’ roles—that of Russian-propped governments obeying the whims of their patron—is but the latest instance of such oversight. Where the results of colonial social and cultural interactions are indelibly stamped across France, Algeria, and every other former (and current) French holding, so to are the Muscovite and Russian colonial ambitions embedded within the modern politics and cultures of both Russia and the Caucasus. Russian colonial artefacts are enhanced and perhaps granted an additional social explanatory edge over those of the ‘typical’ colonizers, by the cyclical adoration for and noisy rejection of European cultural markers over the centuries, along with the somewhat unusual composition of the Cossacks: Russia’s main agents of colonialization within the Caucasian frontier. The story of Russia and Chechnya, of all the Caucasus, is of the manufacture of social and individual identity through “modes of subjectification” inherent within the region’s colonial history and driven by the triangular interactions between three main groups: the Cossacks, the Caucasian Mountain Tribes, and the Russian Metropol. Together, interactions between these social groups worked to shape and transform the lifestyles and institutional pathologies that constitute the Russian and Chechen states and the politics between them. At the core of this (Western) state-building is the simultaneous and seemingly contradictory desire to be more Western and emulate Western cultural and political practices while also desperately grasping for a uniquely Russian identity. This sits somewhat ironically against the backdrop that Russia hosted a frontier-based settler society and had established that distinctly European feature of settler colonialism early in its history—arguably establishing a claim to being the most “colonial” of the colonial powers. There is no doubt that these forces worked to shape contemporary Russian political and social identity—apparent in the mythic popularity of the Cossack in Russian literature, politics, and academic discourse. What needs to be expanded from the current narrative, however, is that beyond the Cossack identity’s attractiveness on the grounds of its tones of freedom and resistance to unjust authority, the identity is rooted in the imperial ambitions and colonial experiences of the Russian state, and is, therefore, a direct marker of domination and subjectification. Adding an unusual dimension to this not-uncommon cultural progression, the Russian state needed to colonize both the Caucases and the Russian Cossacks, appropriating them in much the same way they appropriated the Circassian mountain tribes. The focus of this paper is not to tell yet another story of how one culture entered an area to overpower another but how a ‘powerful,’ ‘modern,’ ‘Western(ish)’ culture was profoundly and continually changed through its contact with a group of tribal ‘savages’ and ‘braves.’Keywords: Russia, chechnya, subjectification, caucasus, cossacks, Ukraine
Procedia PDF Downloads 7654 Synthesis, Computational Studies, Antioxidant and Anti-Inflammatory Bio-Evaluation of 2,5-Disubstituted- 1,3,4-Oxadiazole Derivatives
Authors: Sibghat Mansoor Rana, Muhammad Islam, Hamid Saeed, Hummera Rafique, Muhammad Majid, Muhammad Tahir Aqeel, Fariha Imtiaz, Zaman Ashraf
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The 1,3,4-oxadiazole derivatives Ox-6a-f have been synthesized by incorporating flur- biprofen moiety with the aim to explore the potential of target molecules to decrease the oxidative stress. The title compounds Ox-6a-f were prepared by simple reactions in which a flurbiprofen –COOH group was esterified with methanol in an acid-catalyzed medium, which was then reacted with hydrazine to afford the corresponding hydrazide. The acid hydrazide was then cyclized into 1,3,4-oxadiazole-2-thiol by reacting with CS2 in the presence of KOH. The title compounds Ox-6a-f were synthesized by the reaction of an –SH group with various alkyl/aryl chlorides, which involves an S-alkylation reaction. The structures of the synthesized Ox-6a-f derivatives were ascer- tained by spectroscopic data. The in silico molecular docking was performed against target proteins cyclooxygenase-2 COX-2 (PDBID 5KIR) and cyclooxygenase-1 COX-1 (PDBID 6Y3C) to determine the binding affinity of the synthesized compounds with these structures. It has been inferred that most of the synthesized compounds bind well with an active binding site of 5KIR compared to 6Y3C, and especially compound Ox-6f showed excellent binding affinity (7.70 kcal/mol) among all synthesized compounds Ox-6a-f. The molecular dynamic (MD) simulation has also been performed to check the stability of docking complexes of ligands with COX-2 by determining their root mean square deviation and root mean square fluctuation. Little fluctuation was observed in case of Ox-6f, which forms the most stable complex with COX-2. The comprehensive antioxidant potential of the synthesized compounds has been evaluated by determining their free radical scavenging activity, including DPPH, OH, nitric oxide (NO), and iron chelation assay. The derivative Ox-6f showed promising results with 80.23% radical scavenging potential at a dose of 100 μg/mL while ascorbic acid exhibited 87.72% inhibition at the same dose. The anti-inflammatory activity of the final products has also been performed, and inflammatory markers were assayed, such as a thiobarbituric acid-reducing substance, nitric oxide, interleukin-6 (IL-6), and COX-2. The derivatives Ox-6d and Ox-6f displayed higher anti-inflammatory activity, exhibiting 70.56% and 74.16% activity, respectively. The results were compared with standard ibuprofen, which showed 84.31% activity at the same dose, 200 μg/mL. The anti-inflammatory potential has been performed by following the carrageen-induced hind paw edema model, and results showed that derivative Ox-6f exhibited 79.83% reduction in edema volume compared to standard ibuprofen, which reduced 84.31% edema volume. As dry lab and wet lab results confirm each other, it has been deduced that derivative Ox-6f may serve as the lead structure to design potent compounds to address oxidative stress.Keywords: synthetic chemistry, pharmaceutical chemistry, oxadiazole derivatives, anti-inflammatory, anti-cancer compounds
Procedia PDF Downloads 1553 Linguistic Analysis of Borderline Personality Disorder: Using Language to Predict Maladaptive Thoughts and Behaviours
Authors: Charlotte Entwistle, Ryan Boyd
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Recent developments in information retrieval techniques and natural language processing have allowed for greater exploration of psychological and social processes. Linguistic analysis methods for understanding behaviour have provided useful insights within the field of mental health. One area within mental health that has received little attention though, is borderline personality disorder (BPD). BPD is a common mental health disorder characterised by instability of interpersonal relationships, self-image and affect. It also manifests through maladaptive behaviours, such as impulsivity and self-harm. Examination of language patterns associated with BPD could allow for a greater understanding of the disorder and its links to maladaptive thoughts and behaviours. Language analysis methods could also be used in a predictive way, such as by identifying indicators of BPD or predicting maladaptive thoughts, emotions and behaviours. Additionally, associations that are uncovered between language and maladaptive thoughts and behaviours could then be applied at a more general level. This study explores linguistic characteristics of BPD, and their links to maladaptive thoughts and behaviours, through the analysis of social media data. Data were collected from a large corpus of posts from the publicly available social media platform Reddit, namely, from the ‘r/BPD’ subreddit whereby people identify as having BPD. Data were collected using the Python Reddit API Wrapper and included all users which had posted within the BPD subreddit. All posts were manually inspected to ensure that they were not posted by someone who clearly did not have BPD, such as people posting about a loved one with BPD. These users were then tracked across all other subreddits of which they had posted in and data from these subreddits were also collected. Additionally, data were collected from a random control group of Reddit users. Disorder-relevant behaviours, such as self-harming or aggression-related behaviours, outlined within Reddit posts were coded to by expert raters. All posts and comments were aggregated by user and split by subreddit. Language data were then analysed using the Linguistic Inquiry and Word Count (LIWC) 2015 software. LIWC is a text analysis program that identifies and categorises words based on linguistic and paralinguistic dimensions, psychological constructs and personal concern categories. Statistical analyses of linguistic features could then be conducted. Findings revealed distinct linguistic features associated with BPD, based on Reddit posts, which differentiated these users from a control group. Language patterns were also found to be associated with the occurrence of maladaptive thoughts and behaviours. Thus, this study demonstrates that there are indeed linguistic markers of BPD present on social media. It also implies that language could be predictive of maladaptive thoughts and behaviours associated with BPD. These findings are of importance as they suggest potential for clinical interventions to be provided based on the language of people with BPD to try to reduce the likelihood of maladaptive thoughts and behaviours occurring. For example, by social media tracking or engaging people with BPD in expressive writing therapy. Overall, this study has provided a greater understanding of the disorder and how it manifests through language and behaviour.Keywords: behaviour analysis, borderline personality disorder, natural language processing, social media data
Procedia PDF Downloads 34952 Computational Approaches to Study Lineage Plasticity in Human Pancreatic Ductal Adenocarcinoma
Authors: Almudena Espin Perez, Tyler Risom, Carl Pelz, Isabel English, Robert M. Angelo, Rosalie Sears, Andrew J. Gentles
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Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies. The role of the tumor microenvironment (TME) is gaining significant attention in cancer research. Despite ongoing efforts, the nature of the interactions between tumors, immune cells, and stromal cells remains poorly understood. The cell-intrinsic properties that govern cell lineage plasticity in PDAC and extrinsic influences of immune populations require technically challenging approaches due to the inherently heterogeneous nature of PDAC. Understanding the cell lineage plasticity of PDAC will improve the development of novel strategies that could be translated to the clinic. Members of the team have demonstrated that the acquisition of ductal to neuroendocrine lineage plasticity in PDAC confers therapeutic resistance and is a biomarker of poor outcomes in patients. Our approach combines computational methods for deconvolving bulk transcriptomic cancer data using CIBERSORTx and high-throughput single-cell imaging using Multiplexed Ion Beam Imaging (MIBI) to study lineage plasticity in PDAC and its relationship to the infiltrating immune system. The CIBERSORTx algorithm uses signature matrices from immune cells and stroma from sorted and single-cell data in order to 1) infer the fractions of different immune cell types and stromal cells in bulked gene expression data and 2) impute a representative transcriptome profile for each cell type. We studied a unique set of 300 genomically well-characterized primary PDAC samples with rich clinical annotation. We deconvolved the PDAC transcriptome profiles using CIBERSORTx, leveraging publicly available single-cell RNA-seq data from normal pancreatic tissue and PDAC to estimate cell type proportions in PDAC, and digitally reconstruct cell-specific transcriptional profiles from our study dataset. We built signature matrices and optimized by simulations and comparison to ground truth data. We identified cell-type-specific transcriptional programs that contribute to cancer cell lineage plasticity, especially in the ductal compartment. We also studied cell differentiation hierarchies using CytoTRACE and predict cell lineage trajectories for acinar and ductal cells that we believe are pinpointing relevant information on PDAC progression. Collaborators (Angelo lab, Stanford University) has led the development of the Multiplexed Ion Beam Imaging (MIBI) platform for spatial proteomics. We will use in the very near future MIBI from tissue microarray of 40 PDAC samples to understand the spatial relationship between cancer cell lineage plasticity and stromal cells focused on infiltrating immune cells, using the relevant markers of PDAC plasticity identified from the RNA-seq analysis.Keywords: deconvolution, imaging, microenvironment, PDAC
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