Search results for: traumatic brain injury.
1137 In-Depth Investigations on the Sequences of Accidents of Powered Two Wheelers Based on Police Crash Reports of Medan, North Sumatera Province Indonesia, Using Decision Aiding Processes
Authors: Bangun F., Crevits B., Bellet T., Banet A., Boy G. A., Katili I.
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This paper seeks the incoherencies in cognitive process during an accident of Powered Two Wheelers (PTW) by understanding the factual sequences of events and causal relations for each case of accident. The principle of this approach is undertaking in-depth investigations on case per case of PTW accidents based on elaborate data acquisitions on accident sites that officially stamped in Police Crash Report (PCRs) 2012 of Medan with criteria, involved at least one PTW and resulted in serious injury and fatalities. The analysis takes into account four modules: accident chronologies, perpetrator, and victims, injury surveillance, vehicles and road infrastructures, comprising of traffic facilities, road geometry, road alignments and weather. The proposal for improvement could have provided a favorable influence on the chain of functional processes and events leading to collision. Decision Aiding Processes (DAP) assists in structuring different entities at different decisional levels, as each of these entities has its own objectives and constraints. The entities (A) are classified into 6 groups of accidents: solo PTW accidents; PTW vs. PTW; PTW vs. pedestrian; PTW vs. motor-trishaw; and PTW vs. other vehicles and consecutive crashes. The entities are also distinguished into 4 decisional levels: level of road users and street systems; operational level (crash-attended police officers or CAPO and road engineers), tactical level (Regional Traffic Police, Department of Transportation, and Department of Public Work), and strategic level (Traffic Police Headquarters (TCPHI)), parliament, Ministry of Transportation and Ministry of Public Work). These classifications will lead to conceptualization of Problem Situations (P) and Problem Formulations (I) in DAP context. The DAP concerns the sequences process of the incidents until the time the accident occurs, which can be modelled in terms of five activities of procedural rationality: identification on initial human features (IHF), investigation on proponents attributes (PrAT), on Injury Surveillance (IS), on the interaction between IHF and PrAt and IS (intercorrelation), then unravel the sequences of incidents; filtering and disclosure, which include: what needs to activate, modify or change or remove, what is new and what is priority. These can relate to the activation or modification or new establishment of law. The PrAt encompasses the problems of environmental, road infrastructure, road and traffic facilities, and road geometry. The evaluation model (MP) is generated to bridge P and I since MP is produced by the intercorrelations among IHF, PrAT and IS extracted from the PCRs 2012 of Medan. There are 7 findings of incoherences: lack of knowledge and awareness on the traffic regulations and the risks of accidents, especially when riding between 0 < x < 10 km from house, riding between 22 p.m.–05.30 a.m.; lack of engagements on procurement of IHF Data by CAPO; lack of competency of CAPO on data procurement in accident-sites; no intercorrelation among IHF and PrAt and IS in the database systems of PCRs; lack of maintenance and supervision on the availabilities and the capacities of traffic facilities and road infrastructure; instrumental bias with wash-back impacts towards the TCPHI; technical robustness with wash-back impacts towards the CAPO and TCPHI.Keywords: decision aiding processes, evaluation model, PTW accidents, police crash reports
Procedia PDF Downloads 1581136 Macroscopic Study of Reproductive Pathologies in Cows at the Souk-Ahras Communal Slaughterhouse
Authors: Besma Abdeltif, Chebabhi Imen
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Introduction: it is important to define the genital pathologies encountered in Algeria in postpartum dairy cows. The objective was to identify the different pathologies of reproduction in cows found at the communal abattoir of Souk Ahras. Materials and Methods: Our study was carried at the communal slaughterhouse of Souk-Ahras on 63 genital tracts were examined macroscopically after slaughter. Results: The results obtained reveal a high frequency of pregnant females (14.28%), most of the gestations were at their beginning. Uterine anomalies ranked first in the genital lesions of the cow (20.37%). The frequencies of these abnormalities are in ascending order: aplasia of the horns = 1.85%, traumatic cervical = 1.85%, cervical tumors = 1.85%, chronic endometritis = 3.70% and Acute endometritis = 11.11%. The ovarian cyst is the most common lesion, with a frequency of 3.70%, followed by smooth ovaries (1.85%). These are single, thin-walled cysts more present on the right ovary than the left ovary. Salpingitis is the only tubal lesion found on 5.55% of the non-pregnant genital tract. Neoformation is the only vaginal lesion identified in this work (1.85%). Conclusion: Our result, in general, conforms to the data of the literature.Keywords: genital tract, cow, slaughterhouse, pathology
Procedia PDF Downloads 1061135 The Mediation Effect of PTSD and Aggression on the Relationship of Childhood Physical Abuse and Suicidal Behavior in Homeless People
Authors: Jina Hong, Seongeun Ryu, Sungeun You
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Suicide rate among homeless people are much higher than one in the general population. The purpose of this study was to examine the mediating effect of PTSD and aggression in the relationship between childhood physical abuse and suicidal behavior among homeless people. One hundred one homeless were recruited from street and shelters in Korea. Face-to-face interviews were conducted by master’s level graduate students or facility employees of shelters. All participants completed the Suicidal Behaviors Questionnaire-Revised (SBQ-R), Life History of Aggression Questionnaire (LHAQ), Primary Care PTSD (PC-PTSD), and Traumatic Life Events Questionnaire (TLEQ). The average age of homeless people participated in the study was 55.2 years (SD = 10.7) with the age range of 30 to 87. Results indicated that PTSD symptoms and aggression fully mediated the relationship between childhood physical abuse and suicidal behavior among the homeless. These findings suggest the need for trauma-informed care for the homeless, and warrant the need for psychological services for PTSD and aggression in order to reduce suicide risk among homeless people.Keywords: aggression, homeless, PTSD, suicidal behavior
Procedia PDF Downloads 3811134 CD97 and Its Role in Glioblastoma Stem Cell Self-Renewal
Authors: Niklas Ravn-Boess, Nainita Bhowmick, Takamitsu Hattori, Shohei Koide, Christopher Park, Dimitris Placantonakis
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Background: Glioblastoma (GBM) is the most common and deadly primary brain malignancy in adults. Tumor propagation, brain invasion, and resistance to therapy critically depend on GBM stem-like cells (GSCs); however, the mechanisms that regulate GSC self-renewal are incompletely understood. Given the aggressiveness and poor prognosis of GBM, it is imperative to find biomarkers that could also translate into novel drug targets. Along these lines, we have identified a cell surface antigen, CD97 (ADGRE5), an adhesion G protein-coupled receptor (GPCR), that is expressed on GBM cells but is absent from non-neoplastic brain tissue. CD97 has been shown to promote invasiveness, angiogenesis, and migration in several human cancers, but its frequency of expression and functional role in regulating GBM growth and survival, and its potential as a therapeutic target has not been investigated. Design: We assessed CD97 mRNA and protein expression in patient derived GBM samples and cell lines using publicly available RNA-sequencing datasets and flow cytometry, respectively. To assess CD97 function, we generated shRNA lentiviral constructs that target a sequence in the CD97 extracellular domain (ECD). A scrambled shRNA (scr) with no predicted targets in the genome was used as a control. We evaluated CD97 shRNA lentivirally transduced GBM cells for Ki67, Annexin V, and DAPI. We also tested CD97 KD cells for their ability to self-renew using clonogenic tumorsphere formation assays. Further, we utilized synthetic Abs (sAbs) generated against the ECD of CD97 to test for potential antitumor effects using patient-derived GBM cell lines. Results: CD97 mRNA expression was expressed at high levels in all GBM samples available in the TCGA cohort. We found high levels of surface CD97 protein expression in 6/6 patient-derived GBM cell cultures, but not human neural stem cells. Flow cytometry confirmed downregulation of CD97 in CD97 shRNA lentivirally transduced cells. CD97 KD induced a significant reduction in cell growth in 3 independent GBM cell lines representing mesenchymal and proneural subtypes, which was accompanied by reduced (~20%) Ki67 staining and increased (~30%) apoptosis. Incubation of GBM cells with sAbs (20 ug/ ml) against the ECD of CD97 for 3 days induced GSC differentiation, as determined by the expression of GFAP and Tubulin. Using three unique GBM patient derived cultures, we found that CD97 KD attenuated the ability of GBM cells to initiate sphere formation by over 300 fold, consistent with an impairment in GSC self-renewal. Conclusion: Loss of CD97 expression in patient-derived GBM cells markedly decreases proliferation, induces cell death, and reduces tumorsphere formation. sAbs against the ECD of CD97 reduce tumorsphere formation, recapitulating the phenotype of CD97 KD, suggesting that sAbs that inhibit CD97 function exhibit anti-tumor activity. Collectively, these findings indicate that CD97 is necessary for the proliferation and survival of human GBM cells and identify CD97 as a promising therapeutically targetable vulnerability in GBM.Keywords: adhesion GPCR, CD97, GBM stem cell, glioblastoma
Procedia PDF Downloads 1371133 Early Metastatic Cancer: A Review of Its Management and Outcomes
Authors: Diwei Lin, Amanda Jia Hui Tan
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In 2012, testicular cancer was estimated to account for 940 disability adjusted life years in Australia; of these, 450 were years lost due to premature death and 500 were years of healthy life lost due to disease, disability or injury. Testicular choriocarcinoma is one of the rarest variants of testicular germ cell tumours, accounting for less than 1% of testicular germ cell tumours and only about 0.19% of all testicular tumours. Management involves radical orchiectomy followed by chemotherapy. Even then, the prognosis is extremely poor. This case report describes a 20-year-old male with pure testicular choriocarcinoma with pulmonary metastases.Keywords: testicular cancer, choriocarcinoma, cryptorchidism, chemotherapy, metastatic testicular cancer
Procedia PDF Downloads 3631132 Defective Autophagy Disturbs Neural Migration and Network Activity in hiPSC-Derived Cockayne Syndrome B Disease Models
Authors: Julia Kapr, Andrea Rossi, Haribaskar Ramachandran, Marius Pollet, Ilka Egger, Selina Dangeleit, Katharina Koch, Jean Krutmann, Ellen Fritsche
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It is widely acknowledged that animal models do not always represent human disease. Especially human brain development is difficult to model in animals due to a variety of structural and functional species-specificities. This causes significant discrepancies between predicted and apparent drug efficacies in clinical trials and their subsequent failure. Emerging alternatives based on 3D in vitro approaches, such as human brain spheres or organoids, may in the future reduce and ultimately replace animal models. Here, we present a human induced pluripotent stem cell (hiPSC)-based 3D neural in a vitro disease model for the Cockayne Syndrome B (CSB). CSB is a rare hereditary disease and is accompanied by severe neurologic defects, such as microcephaly, ataxia and intellectual disability, with currently no treatment options. Therefore, the aim of this study is to investigate the molecular and cellular defects found in neural hiPSC-derived CSB models. Understanding the underlying pathology of CSB enables the development of treatment options. The two CSB models used in this study comprise a patient-derived hiPSC line and its isogenic control as well as a CSB-deficient cell line based on a healthy hiPSC line (IMR90-4) background thereby excluding genetic background-related effects. Neurally induced and differentiated brain sphere cultures were characterized via RNA Sequencing, western blot (WB), immunocytochemistry (ICC) and multielectrode arrays (MEAs). CSB-deficiency leads to an altered gene expression of markers for autophagy, focal adhesion and neural network formation. Cell migration was significantly reduced and electrical activity was significantly increased in the disease cell lines. These data hint that the cellular pathologies is possibly underlying CSB. By induction of autophagy, the migration phenotype could be partially rescued, suggesting a crucial role of disturbed autophagy in defective neural migration of the disease lines. Altered autophagy may also lead to inefficient mitophagy. Accordingly, disease cell lines were shown to have a lower mitochondrial base activity and a higher susceptibility to mitochondrial stress induced by rotenone. Since mitochondria play an important role in neurotransmitter cycling, we suggest that defective mitochondria may lead to altered electrical activity in the disease cell lines. Failure to clear the defective mitochondria by mitophagy and thus missing initiation cues for new mitochondrial production could potentiate this problem. With our data, we aim at establishing a disease adverse outcome pathway (AOP), thereby adding to the in-depth understanding of this multi-faced disorder and subsequently contributing to alternative drug development.Keywords: autophagy, disease modeling, in vitro, pluripotent stem cells
Procedia PDF Downloads 1201131 Self-Inflicted Major Trauma: Inpatient Mental Health Management and Patient Outcomes
Authors: M. Walmsley, S. Elmatarri, S. Mannion
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Introduction: Self-inflicted injury is a recognised cause of major trauma in adults and is an independent indicator of a reduced functional outcome compared to non-intentional major trauma. There is little literature available on the inpatient mental health (MH) management of this vulnerable group. A retrospective review was conducted of inpatient MH management of major trauma patients admitted to a UK regional Major Trauma Centre (MTC). Their outcomes were compared to all major trauma patients. This group of patients required multiple MH interventions whilst on the Major Trauma Ward (MTW) and a had worse functional outcome compared to non-intentional trauma. Method: The national TARN (Trauma Audit and Research Network) database was used to identify patients admitted to a regional MTC over a 2-year period from June 2018 to July 2020. Patients with an ISS (Injury Severity Score) of greater than 15 with a mechanism of either self-harm or high-risk behavior were included for further analysis. Inpatient medical notes were reviewed for MH interventions on the MTW. Further outcomes, including mortality, length of stay (LOS) and Glasgow Outcome Score (GOS) were compared with all major trauma patients for the same time period. Results: A total of 60 patients were identified in the time period and of those, 27 spent time on the MTW. A total of 23 (85%) had a prior MH diagnosis, with 11 (41%) under the care of secondary MH services. Adequate inpatient records for review were available for 24 patients. During their inpatient stay, 8 (33%) were reviewed on the ward by the inpatient MH team. There were 10 interventions required for 6 (25%) patients on the MTW including, sections under the Mental Health Act, transfer to specialist MH facility, pharmacological sedation and security being called to the MTW. When compared to all major trauma patients, those admitted due to self-harm or high-risk behavior had a statistically significantly higher ISS (31.43 vs 24.22, p=0.0001) and LOS (23.51d vs 16.06d, p=0.002). Functional outcomes using the GOS were reduced in this group of patients, GOS 5 (low disability) (51.66% vs. 61.01%) and they additionally had a higher level of mortality, GOS 1 (15.00% vs 11.67%). Discussion: Intentional self-harm is a recognised cause of major trauma in adults and this patient group sustains more severe injuries, requiring a longer hospital stay with worse outcomes compared to all major trauma patients. Inpatient MH interventions are required for a significant proportion of these patients and therefore, there needs to be a close relationship with MH services. There is limited available evidence for how this patient group is best managed as an inpatient to aid their recovery and further work is needed on how outcomes in this vulnerable group can be improved.Keywords: adult major trauma, attempted suicide, self-inflicted major trauma, inpatient management
Procedia PDF Downloads 1821130 Comparative Efficacy of Angiotensin Converting Enzymes Inhibitors and Angiotensin Receptor Blockers in Patients with Heart Failure in Tanzania: A Prospective Cohort Study
Authors: Mark P. Mayala, Henry Mayala, Khuzeima Khanbhai
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Background: Heart failure has been a rising concern in Tanzania. New drugs have been introduced, including the group of drugs called Angiotensin receptor Neprilysin Inhibitor (ARNI), but due to their high cost, angiotensin-converting enzymes inhibitors (ACEIs) and Angiotensin receptor blockers (ARBs) have been mostly used in Tanzania. However, according to our knowledge, the efficacy comparison of the two groups is yet to be studied in Tanzania. The aim of this study was to compare the efficacy of ACEIs and ARBs among patients with heart failure. Methodology: This was a hospital-based prospective cohort study done at Jakaya Kikwete Cardiac Institution (JKCI), Tanzania, from June to December 2020. Consecutive enrollment was done until fulfilling the inclusion criteria. Clinical details were measured at baseline. We assessed the relationship between ARBs and ACEIs users with N-terminal pro-brain natriuretic peptide (NT pro-BNP) levels at admission and at 1-month follow-up using a chi-square test. A Kaplan-Meier curve was used to estimate the survival time of the two groups. Results: 155 HF patients were enrolled, with a mean age of 48 years, whereby 52.3% were male, and their mean left ventricular ejection fraction (LVEF) was 37.3%. 52 (33.5%) heart failure patients were on ACEIs, 57 (36.8%) on ARBs, and 46 (29.7%) were neither using ACEIs nor ARBs. At least half of the patients did not receive a guideline-directed medical therapy (GDMT), with only 82 (52.9%) receiving a GDMT. A drop in NT pro-BNP levels was observed during admission and at 1-month follow-up on both groups, from 6389.2 pg/ml to 4000.1 pg/ml for ARB users and 5877.7 pg/ml to 1328.2 pg/ml for the ACEIs users. There was no statistical difference between the two groups when estimated by the Kaplan-Meier curve, though more deaths were observed in those who were neither on ACEIs nor ARBs, with a calculated P value of 0.01. Conclusion: This study demonstrates that ACEIs have more efficacy and overall better clinical outcome than ARBs, but this should be taken under the patient-based case, considering the side effects of ACEIs and patients’ adherence.Keywords: angiotensin converting enzymes inhibitors, angiotensin receptor blockers, guideline direct medical therapy, N-terminal pro-brain natriuretic peptide
Procedia PDF Downloads 851129 Multi-omics Integrative Analysis with Genome-Scale Metabolic Model Simulation Reveals Reaction Essentiality data in Human Astrocytes Under the Lipotoxic Effect of Palmitic Acid
Authors: Janneth Gonzalez, Andres Pinzon Velasco, Maria Angarita, Nicolas Mendoza
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Astrocytes play an important role in various processes in the brain, including pathological conditions such as neurodegenerative diseases. Recent studies have shown that the increase in saturated fatty acids such as palmitic acid (PA) triggers pro-inflammatory pathways in the brain. The use of synthetic neurosteroids such as tibolone has demonstrated neuro-protective mechanisms. However, there are few studies on the neuro-protective mechanisms of tibolone, especially at the systemic (omic) level. In this study, we performed the integration of multi-omic data (transcriptome and proteome) into a human astrocyte genomic scale metabolic model to study the astrocytic response during palmitate treatment. We evaluated metabolic fluxes in three scenarios (healthy, induced inflammation by PA, and tibolone treatment under PA inflammation). We also use control theory to identify those reactions that control the astrocytic system. Our results suggest that PA generates a modulation of central and secondary metabolism, showing a change in energy source use through inhibition of folate cycle and fatty acid β-oxidation and upregulation of ketone bodies formation.We found 25 metabolic switches under PA-mediated cellular regulation, 9 of which were critical only in the inflammatory scenario but not in the protective tibolone one. Within these reactions, inhibitory, total, and directional coupling profiles were key findings, playing a fundamental role in the (de)regulation in metabolic pathways that increase neurotoxicity and represent potential treatment targets. Finally, this study framework facilitates the understanding of metabolic regulation strategies, andit can be used for in silico exploring the mechanisms of astrocytic cell regulation, directing a more complex future experimental work in neurodegenerative diseases.Keywords: astrocytes, data integration, palmitic acid, computational model, multi-omics, control theory
Procedia PDF Downloads 1211128 High Injury Prevalence in Adolescent Field Hockey Players: Implications for Future Practice
Authors: Pillay J. D., D. De Wit, J. F. Ducray
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Field hockey is a popular international sport which is played in more than 100 countries across the world. Due to the nature of hockey, players repeatedly perform a combination of forward flexion and rotational movements of the spine in order to strike the ball. These movements have been shown to increase the risk of pain and injury to the lumbar spine. The aim of this study was to determine the prevalence and incidence of low back pain (LBP) in male adolescent field hockey players and the characteristics of LBP in terms of location, chronicity, disability, and treatment sought, as well as its association with selected risk factors. A survey was conducted on 112 male adolescent field hockey players in the eThekwini Municipality of KwaZulu-Natal, South Africa. The questionnaire contained sections on the demographics of participants, general characteristics of participants, health and lifestyle characteristics, low back pain patterns, treatment of low back pain, and the level of disability associated with LBP. The data were statistically analysed using IBM SPSS version 25 with statistical significance set at p-value <0.05. Descriptive statistics such as mean and standard deviation were used to summarise responses to continuous variables as appropriate. Categorical variables were described using frequency tables. Associations between risk factors and low back pain were tested using Pearson’s chi-square test and t-tests as appropriate. A total of 68 questionnaires were completed for analysis (67% participation rate); the period prevalence of LBP was 63.2% (35.0%:beginning of the season, 32.4%:mid-season, 22.1%: end of season). Incidence was 38.2%. The most common location for LBP was the middle low back region (39.5%), and the most common duration of pain was a few hours (32.6%). Most participants (79.1%) did not classify their pain as a disability, and only 44.2% of participants received medical treatment for their LBP. An interesting finding was the association between hydration and LBP (p = 0.050), i.e., those individuals who did not hydrate frequently during matches and training were significantly more likely to experience LBP. The results of this study, although limited to a select group of adolescents, showed a higher prevalence of LBP than that of previous studies. More importantly, even though most participants did not experience LBP classified as a disability, LBP still had a large impact on participants, as nearly half of the participants consulted with a medical professional for treatment. Need for the application of further strategies in the prevention and management of LBP in field hockey, such as adequate warm-up and cool-down, stretching exercises, rest between sessions, etc., are recommended as simple strategies to reduce LBP prevalence.Keywords: adolescents, field hockey players, incidence, low back pain, prevalence, risk factors
Procedia PDF Downloads 571127 Phorbol 12-Myristate 13-Acetate (PMA)-Differentiated THP-1 Monocytes as a Validated Microglial-Like Model in Vitro
Authors: Amelia J. McFarland, Andrew K. Davey, Shailendra Anoopkumar-Dukie
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Microglia are the resident macrophage population of the central nervous system (CNS), contributing to both innate and adaptive immune response, and brain homeostasis. Activation of microglia occurs in response to a multitude of pathogenic stimuli in their microenvironment; this induces morphological and functional changes, resulting in a state of acute neuroinflammation which facilitates injury resolution. Adequate microglial function is essential for the health of the neuroparenchyma, with microglial dysfunction implicated in numerous CNS pathologies. Given the critical role that these macrophage-derived cells play in CNS homeostasis, there is a high demand for microglial models suitable for use in neuroscience research. The isolation of primary human microglia, however, is both difficult and costly, with microglial activation an unwanted but inevitable result of the extraction process. Consequently, there is a need for the development of alternative experimental models which exhibit morphological, biochemical and functional characteristics of human microglia without the difficulties associated with primary cell lines. In this study, our aim was to evaluate whether THP-1 human peripheral blood monocytes would display microglial-like qualities following an induced differentiation, and, therefore, be suitable for use as surrogate microglia. To achieve this aim, THP-1 human peripheral blood monocytes from acute monocytic leukaemia were differentiated with a range of phorbol 12-myristate 13-acetate (PMA) concentrations (50-200 nM) using two different protocols: a 5-day continuous PMA exposure or a 3-day continuous PMA exposure followed by a 5-day rest in normal media. In each protocol and at each PMA concentration, microglial-like cell morphology was assessed through crystal violet staining and the presence of CD-14 microglial / macrophage cell surface marker. Lipopolysaccharide (LPS) from Escherichia coli (055: B5) was then added at a range of concentrations from 0-10 mcg/mL to activate the PMA-differentiated THP-1 cells. Functional microglial-like behavior was evaluated by quantifying the release of prostaglandin (PG)-E2 and pro-inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α using mediator-specific ELISAs. Furthermore, production of global reactive oxygen species (ROS) and nitric oxide (NO) were determined fluorometrically using dichlorodihydrofluorescein diacetate (DCFH-DA) and diaminofluorescein diacetate (DAF-2-DA) respectively. Following PMA-treatment, it was observed both differentiation protocols resulted in cells displaying distinct microglial morphology from 10 nM PMA. Activation of differentiated cells using LPS significantly augmented IL-1β, TNF-α and PGE2 release at all LPS concentrations under both differentiation protocols. Similarly, a significant increase in DCFH-DA and DAF-2-DA fluorescence was observed, indicative of increases in ROS and NO production. For all endpoints, the 5-day continuous PMA treatment protocol yielded significantly higher mediator levels than the 3-day treatment and 5-day rest protocol. Our data, therefore, suggests that the differentiation of THP-1 human monocyte cells with PMA yields a homogenous microglial-like population which, following stimulation with LPS, undergo activation to release a range of pro-inflammatory mediators associated with microglial activation. Thus, the use of PMA-differentiated THP-1 cells represents a suitable microglial model for in vitro research.Keywords: differentiation, lipopolysaccharide, microglia, monocyte, neuroscience, THP-1
Procedia PDF Downloads 3881126 Work-Related Shoulder Lesions and Labor Lawsuits in Brazil: Cross-Sectional Study on Worker Health Actions Developed by Employers
Authors: Reinaldo Biscaro, Luciano R. Ferreira, Leonardo C. Biscaro, Raphael C. Biscaro, Isabela S. Vasconcelos, Laura C. R. Ferreira, Cristiano M. Galhardi, Erica P. Baciuk
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Introduction: The present study had the objective to present the profile of workers with shoulder disorders related to labor lawsuits in Brazil. The study analyzed the association between the worker’s health and the actions performed by the companies related to injured professional. The research method performed a retrospective, cross-sectional and quantitative database analysis. The documents of labor lawsuits with shoulder injury registered at the Regional Labor Court in the 15th region (Campinas - São Paulo) were submitted to the medical examination and evaluated during the period from 2012 until 2015. The data collected were age, gender, onset of symptoms, length of service, current occupation, type of shoulder injury, referred complaints, type of acromion, associated or related diseases, company actions as CAT (workplace accident communication), compliance of NR7 by the organization (Environmental Risk Prevention Program - PPRA and Medical Coordination Program in Occupational Health - PCMSO). Results: From the 93 workers evaluated, there was a prevalence of men (58.1%), with a mean age of 42.6 y-o, and 54.8% were included in the age group 35-49 years. Regarding the length of work time in the company, 66.7% have worked for more than 5 years. There was an association between gender and current occupational status (p < 0.005), with predominance of women in household occupation (13 vs. 2) and predominance of unemployed men in job search situation (24 vs. 10) and reintegrated to work by judicial decision (8 vs. 2). There was also a correlation between pain and functional limitation (p < 0.01). There was a positive association of PPRA with the complaint of functional limitation and negative association with pain (p < 0.04). There was also a correlation between the sedentary lifestyle and the presence of PCMSO and PPRA (p < 0.04), and the absence of CAT in the companies (p < 0.001). It was concluded that the appearance or aggravation of osseous and articular shoulder pathologies in workers who have undertaken labor law suits seem to be associated with individual habits or inadequate labor practices. These data can help preventing the occurrence of these lesions by implementing local health promotion policies at work.Keywords: work-related accidents, cross-sectional study, shoulder lesions, labor lawsuits
Procedia PDF Downloads 2181125 The Functional Magnetic Resonance Imaging and the Consumer Behaviour: Reviewing Recent Research
Authors: Mikel Alonso López
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In the first decade of the twenty-first century, advanced imaging techniques began to be applied for neuroscience research. The Functional Magnetic Resonance Imaging (fMRI) is one of the most important and most used research techniques for the investigation of emotions, because of its ease to observe the brain areas that oxygenate when performing certain tasks. In this research, we make a review about the main research carried out on the influence of the emotions in the decision-making process that is exposed by using the fMRI.Keywords: decision making, emotions, fMRI, consumer behaviour
Procedia PDF Downloads 4791124 Migrant Youth: Trauma-Informed Interventions
Authors: Nancy Daly
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Migrant youth who have experienced traumatic events in their home countries or in their passage to the United States may require interventions or formal services to support varying levels and types of needs. The manner in which such youth are engaged and evaluated, as well as the framework of evaluation, can impact their educational services and placement. Evidenced-based trauma-informed practices that engage and support migrant youth serve as an important bridge to stabilization; however, ensuring long-term growth may require a range of integrated services, including special education and mental health services. Special education evaluations which consider the eligibility of Emotional Disturbance for migrant youth must carefully weigh issues of mental health needs against the exclusionary criteria of lack of access to education, limited language skills, as well as other environmental factors. Case studies of recently arrived migrant youth reveal both commonalities and differences in types and levels of need which underscores the importance of adept evaluation and case management to ensure the provision of services that support growth and resiliency.Keywords: migrant youth, trauma-informed care, mental health services, special education
Procedia PDF Downloads 1251123 Concepts of Instrumentation Scheme for Thought Transfer
Authors: Rai Sachindra Prasad
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Thought is physical force. This has been well recognized but hardly translated visually or otherwise in the sense of its transfer from one individual to another. In the present world of chaos and disorder with yawning gaps between right and wrong thinking individuals, if it is possible to transfer the right thoughts to replace the wrong ones it would indeed be a great achievement in the present situation of the world which is torn with violence with dangerous thoughts of individuals. Moreover, such a possibility would completely remove the barrier of language between two persons, which at times proves to be a great obstacle in realizing a desired purpose. If a proper instrumentation scheme containing appropriate transducers and electronics is designed and implemented to realize this thought ransfer phenomenon, this would prove to be extremely useful when properly used. Considering the advancements already made in recording the nerve impulses in the brain, which are electrical events of very short durations that move along the axon, it is conceivable that this may be used to good effect in implementing the scheme. In such a proposition one shoud consider the roles played by pineal body, pituitary gland and ‘association’ areas. Pioneer students of brain have thought that associations or connections between sensory input and motor output were made in these areas. It is currently believed that rather than being regions of simple sensory-motor connections, the association areas process and integrate sensory information relayed to them from the primary sensory areas of the cortex and from the thalamus, after the information has been processed, it may be sent to motor areas to be acted upon. Again, even though the role played by pineal body is not known fully to neurologists its interconnection with pituitary gland is a matter of great significance to the ‘Rishis’ and; Seers’ s described in Vedas and Puranas- the ancient Holy books of Hindus. If the pineal body is activated through meditation it would control the pituitary gland thereby the individual’s thoughts and acts. Thus, if thoughts can be picked up by special transducers, these can be connected to suitable electronics circuitry to amplify the signals. These signals in the form of electromagnetic waves can then be transmitted using modems for long distance transmission and eventually received by or passed on to a subject of interest through another set of electronics circuit and devices.Keywords: modems, pituitary gland, pineal body, thought transfer
Procedia PDF Downloads 3721122 Sportomics Analysis of Metabolic Responses in Olympic Sprint Canoeists
Authors: A. Magno-França, A. M. Magalhães-Neto, F. Bachini, E. Cataldi, A. Bassini, L. C. Cameron
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Sprint canoeing (SC) is part of the Olympic Games since 1936. Athletes compete in solo or double races of 200m and 1000m (40 sec and 240 sec, respectively). Due to its high intensity and duration, SC is extremely useful to study the blood kinetics of some metabolites in high energetic demand. Sportomics is a field of study combining “-omics” sciences with classical biochemical analyses in order to understand sports induced systemic changes. Here, we compare Sportomics findings during SC training sessions to describe metabolic responses of five top-level canoeists. Five Olympic world-class male athletes were evaluated during two days of training.Keywords: biochemistry of exercise, metabolomics, injury markers, sportomics
Procedia PDF Downloads 5161121 Rapid and Sensitive Detection: Biosensors as an Innovative Analytical Tools
Authors: Sylwia Baluta, Joanna Cabaj, Karol Malecha
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The evolution of biosensors was driven by the need for faster and more versatile analytical methods for application in important areas including clinical, diagnostics, food analysis or environmental monitoring, with minimum sample pretreatment. Rapid and sensitive neurotransmitters detection is extremely important in modern medicine. These compounds mainly occur in the brain and central nervous system of mammals. Any changes in the neurotransmitters concentration may lead to many diseases, such as Parkinson’s or schizophrenia. Classical techniques of chemical analysis, despite many advantages, do not permit to obtain immediate results or automatization of measurements.Keywords: adrenaline, biosensor, dopamine, laccase, tyrosinase
Procedia PDF Downloads 1421120 Subjective Evaluation of Mathematical Morphology Edge Detection on Computed Tomography (CT) Images
Authors: Emhimed Saffor
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In this paper, the problem of edge detection in digital images is considered. Three methods of edge detection based on mathematical morphology algorithm were applied on two sets (Brain and Chest) CT images. 3x3 filter for first method, 5x5 filter for second method and 7x7 filter for third method under MATLAB programming environment. The results of the above-mentioned methods are subjectively evaluated. The results show these methods are more efficient and satiable for medical images, and they can be used for different other applications.Keywords: CT images, Matlab, medical images, edge detection
Procedia PDF Downloads 3361119 Neural Network Analysis Applied to Risk Prediction of Early Neonatal Death
Authors: Amanda R. R. Oliveira, Caio F. F. C. Cunha, Juan C. L. Junior, Amorim H. P. Junior
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Children deaths are traumatic events that most often can be prevented. The technology of prevention and intervention in cases of infant deaths is available at low cost and with solid evidence and favorable results, however, with low access cover. Weight is one of the main factors related to death in the neonatal period, so the newborns of low birth weight are a population at high risk of death in the neonatal period, especially early neonatal period. This paper describes the development of a model based in neural network analysis to predict the mortality risk rating in the early neonatal period for newborns of low birth weight to identify the individuals of this population with increased risk of death. The neural network applied was trained with a set of newborns data obtained from Brazilian health system. The resulting network presented great success rate in identifying newborns with high chances of death, which demonstrates the potential for using this tool in an integrated manner to the health system, in order to direct specific actions for improving prognosis of newborns.Keywords: low birth weight, neonatal death risk, neural network, newborn
Procedia PDF Downloads 4481118 Association between Attention Deficit Hyperactivity Disorder Medication, Cannabis, and Nicotine Use, Mental Distress, and Other Psychoactive Substances
Authors: Nicole Scott, Emily Dwyer, Cara Patrissy, Samantha Bonventre, Lina Begdache
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Across North America, the use and abuse of Attention Deficit Hyperactivity Disorder (ADHD) medication, cannabis, nicotine, and other psychoactive substances across college campuses have become an increasingly prevalent problem. Students frequently use these substances to aid their studying or deal with their mental health issues. However, it is still unknown what psychoactive substances are likely to be abused when college students illicitly use ADHD medication. In addition, it is not clear which psychoactive substance is associated with mental distress. Thus, the purpose of this study is to fill these gaps by assessing the use of different psychoactive substances when illicit ADHD medication is used; and how this association relates to mental stress. A total of 702 undergraduate students from different college campuses in the U.S. completed an anonymous survey distributed online. Data were self-reported on demographics, the use of ADHD medications, cannabis, nicotine, other psychoactive drugs, and mental distress, and feelings and opinions on the use of illicit study drugs were all included in the survey. Mental distress was assessed using the Kessler Psychological Distress 6 Scale. Data were analyzed in SPSS, Version 25.0, using Pearson’s Correlation Coefficient. Our results show that use of ADHD medication, cannabis use (non-frequent and very frequent), and nicotine use (non-frequent and very frequent), there were both statistically significant positive and negative correlations to specific psychoactive substances and their corresponding frequencies. Along the same lines, ADHD medication, cannabis use (non-frequent and very frequent), and nicotine use (non-frequent and very frequent) had statistically significant positive and negative correlations to specific mental distress experiences. As these findings are combined, a vicious loop can initiate a cycle where individuals who abuse psychoactive substances may or may not be inclined to use other psychoactive substances. This may later inhibit brain functions in those main areas of the brain stem, amygdala, and prefrontal cortex where this vicious cycle may or may not impact their mental distress. Addressing the impact of study drug abuse and its potential to be associated with further substance abuse may provide an educational framework and support proactive approaches to promote awareness among college students.Keywords: stimulant, depressant, nicotine, ADHD medication, psychoactive substances, mental health, illicit, ecstasy, adrenochrome
Procedia PDF Downloads 631117 Common Health Problems of Filipino Overseas Household Service Workers: Implications for Wellness
Authors: Veronica Ramirez
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For over 40 years now, the Philippines has been supplying Household Service Workers (HSWs) globally. As a requirement of the Philippine Overseas Employment Agency (POEA), all Filipinos applying for overseas work undergo medical examination and a certificate of good health is submitted to the foreign employer before hiring. However, there are workplace-related health problems that develop during employment such as musculoskeletal strain or injury, back pain, hypertension and other illnesses. Some workers are in good working conditions but are on call more than 12 hours per day. There are also those who experience heavy physical work with short rest periods or time off. They can also be easily exposed to disease outbreaks and epidemics. It was the objective of this study to determine the common health problems of Filipino Overseas Service Workers and analyze their implications to wellness in the workplace. Specifically, it sought to describe the work conditions of HSWs and determine the work-related factors affecting their health. It also identified the medical care they avail of and how they perceive their health and wellness as determinants of well-being. Finally, it proposes ways to promote wellness among HSWs. This study focused on physical illnesses and does not include mental problems experienced by HSWs. Using a questionnaire, primary data were gathered online and through survey of HSW rehires who were retaking Pre-Departure Orientation Seminar at recruitment agencies. The 2010 Health Benefit Availment data from the Overseas Workers Welfare Administration (OWWA) was also utilized. Descriptive analysis was employed on the data gathered. Key stakeholders in the migration industry were also interviewed. Previous research studies, reports and literature on migration and wellness were used as secondary data. The study found that Filipino overseas HSWs are vulnerable to physical injury and experience body pains such as back, hip and shoulder pain. Long hours of work, work hazards and lack of rest due to poor accommodations can aggravate their physical condition. Although health insurance and health care are available, HSWs are not aware how to avail them. On the basis of the findings, a Wellness Program can be designed that include health awareness, health care availment, occupational ergonomics, safety and health, work and leisure balance, developing emotional intelligence, anger management and spirituality.Keywords: health, household service worker, overseas, wellness
Procedia PDF Downloads 2581116 Multi-Omics Integrative Analysis Coupled to Control Theory and Computational Simulation of a Genome-Scale Metabolic Model Reveal Controlling Biological Switches in Human Astrocytes under Palmitic Acid-Induced Lipotoxicity
Authors: Janneth Gonzalez, Andrés Pinzon Velasco, Maria Angarita
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Astrocytes play an important role in various processes in the brain, including pathological conditions such as neurodegenerative diseases. Recent studies have shown that the increase in saturated fatty acids such as palmitic acid (PA) triggers pro-inflammatorypathways in the brain. The use of synthetic neurosteroids such as tibolone has demonstrated neuro-protective mechanisms. However, broad studies with a systemic point of view on the neurodegenerative role of PA and the neuro-protective mechanisms of tibolone are lacking. In this study, we performed the integration of multi-omic data (transcriptome and proteome) into a human astrocyte genomic scale metabolic model to study the astrocytic response during palmitate treatment. We evaluated metabolic fluxes in three scenarios (healthy, induced inflammation by PA, and tibolone treatment under PA inflammation). We also applied a control theory approach to identify those reactions that exert more control in the astrocytic system. Our results suggest that PA generates a modulation of central and secondary metabolism, showing a switch in energy source use through inhibition of folate cycle and fatty acid β‐oxidation and upregulation of ketone bodies formation. We found 25 metabolic switches under PA‐mediated cellular regulation, 9 of which were critical only in the inflammatory scenario but not in the protective tibolone one. Within these reactions, inhibitory, total, and directional coupling profiles were key findings, playing a fundamental role in the (de)regulation of metabolic pathways that may increase neurotoxicity and represent potential treatment targets. Finally, the overall framework of our approach facilitates the understanding of complex metabolic regulation, and it can be used for in silico exploration of the mechanisms of astrocytic cell regulation, directing a more complex future experimental work in neurodegenerative diseases.Keywords: astrocytes, data integration, palmitic acid, computational model, multi-omics
Procedia PDF Downloads 971115 The Social Construction of the Family among the Survivors of Sex Trafficking
Authors: Nisha James, Shubha Ranganathan
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Sex trafficking is a traumatic ongoing process which includes human rights violations against the victims. Majority of the trafficked individuals in India are from families with low socioeconomic status, from rural areas, unmarried or married off at a very young age. Many of the sex trafficked feel that it is necessary to make sacrifices, for the benefit of their families. The combination of these cultural family values with the stigma of rape and prostitution are manipulated and used as a tool in the abuse of power against the sex trafficked. The rescue, rehabilitation and reintegration of these individuals are usually difficult due to the stigma and social exclusion that they face. In these circumstances, social support is very effective in social inclusion of these individuals. The present study was a qualitative one, using semi-structured interviews with 29 Indian survivors of sex trafficking and a few sex workers. Thematic analysis was done on the data derived from the semi-structured interviews. The major findings indicate that the family can be seen as both the ‘cause’ for being sex trafficked, and the factor in victim continuing to be sex trafficked. At the same time, it can also become a driver for getting rescued, rehabilitated and reintegrated. The study also explores the social construction about ‘family’ among the survivors of sex trafficking, reflecting on who they refer to as ‘family’, what they mean by the term ‘family’ and how these families emerge. Therefore the analytic concept of ‘family’ is a crucial element in sex trafficking and cannot be defined only in terms of its conventional definition of a basic unit of society.Keywords: sex-trafficking, survivor, family, social construction
Procedia PDF Downloads 5911114 Exploring the Neural Mechanisms of Communication and Cooperation in Children and Adults
Authors: Sara Mosteller, Larissa K. Samuelson, Sobanawartiny Wijeakumar, John P. Spencer
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This study was designed to examine how humans are able to teach and learn semantic information as well as cooperate in order to jointly achieve sophisticated goals. Specifically, we are measuring individual differences in how these abilities develop from foundational building blocks in early childhood. The current study adopts a paradigm for novel noun learning developed by Samuelson, Smith, Perry, and Spencer (2011) to a hyperscanning paradigm [Cui, Bryant and Reiss, 2012]. This project measures coordinated brain activity between a parent and child using simultaneous functional near infrared spectroscopy (fNIRS) in pairs of 2.5, 3.5 and 4.5-year-old children and their parents. We are also separately testing pairs of adult friends. Children and parents, or adult friends, are seated across from one another at a table. The parent (in the developmental study) then teaches their child the names of novel toys. An experimenter then tests the child by presenting the objects in pairs and asking the child to retrieve one object by name. Children are asked to choose from both pairs of familiar objects and pairs of novel objects. In order to explore individual differences in cooperation with the same participants, each dyad plays a cooperative game of Jenga, in which their joint score is based on how many blocks they can remove from the tower as a team. A preliminary analysis of the noun-learning task showed that, when presented with 6 word-object mappings, children learned an average of 3 new words (50%) and that the number of objects learned by each child ranged from 2-4. Adults initially learned all of the new words but were variable in their later retention of the mappings, which ranged from 50-100%. We are currently examining differences in cooperative behavior during the Jenga playing game, including time spent discussing each move before it is made. Ongoing analyses are examining the social dynamics that might underlie the differences between words that were successfully learned and unlearned words for each dyad, as well as the developmental differences observed in the study. Additionally, the Jenga game is being used to better understand individual and developmental differences in social coordination during a cooperative task. At a behavioral level, the analysis maps periods of joint visual attention between participants during the word learning and the Jenga game, using head-mounted eye trackers to assess each participant’s first-person viewpoint during the session. We are also analyzing the coherence in brain activity between participants during novel word-learning and Jenga playing. The first hypothesis is that visual joint attention during the session will be positively correlated with both the number of words learned and with the number of blocks moved during Jenga before the tower falls. The next hypothesis is that successful communication of new words and success in the game will each be positively correlated with synchronized brain activity between the parent and child/the adult friends in cortical regions underlying social cognition, semantic processing, and visual processing. This study probes both the neural and behavioral mechanisms of learning and cooperation in a naturalistic, interactive and developmental context.Keywords: communication, cooperation, development, interaction, neuroscience
Procedia PDF Downloads 2521113 Consequences of Inadequate Funding in Nigerian Educational System
Authors: Sylvia Nkiru Ogbuoji
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This paper discussed the consequences of inadequate funding in Nigerian education system. It briefly explained the meaning of education in relation to the context and identified various ways education in Nigeria can be funded. It highlighted some of the consequences of inadequate funding education system to include: Inadequate facilitates for teaching and learning, western brain drain, unemployment, crises of poverty, low staff morale it. Finally, some recommendations were put forward, the government should improve the annual budget allocation to education, in order to achieve educational objective, also government should monitor the utilization of allocated funds to minimize embezzlement.Keywords: consequences, corruption, education, funding
Procedia PDF Downloads 4521112 Forensic Detection of Errors Permitted by the Witnesses in Their Testimony
Authors: Lev Bertovsky
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The purpose of this study was to determine the reasons for the formation of false testimony from witnesses and make recommendations on the recognition of such cases. During the studies, which were based on the achievements of professionals in the field of psychology, as well as personal investigative practice, the stages of perception of the information were studied, as well as the process of its reclaim from the memory and transmission to the communicator upon request. Based on the principles of the human brain, kinds of conscientious witness mistakes were systematized. Proposals were formulated for the optimization of investigative actions in cases where the witnesses make an honest mistake with respect to the effects previously observed by them.Keywords: criminology, eyewitness testimony, honest mistake, information, investigator, investigation, questioning
Procedia PDF Downloads 1851111 Epileptic Seizure Prediction by Exploiting Signal Transitions Phenomena
Authors: Mohammad Zavid Parvez, Manoranjan Paul
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A seizure prediction method is proposed by extracting global features using phase correlation between adjacent epochs for detecting relative changes and local features using fluctuation/deviation within an epoch for determining fine changes of different EEG signals. A classifier and a regularization technique are applied for the reduction of false alarms and improvement of the overall prediction accuracy. The experiments show that the proposed method outperforms the state-of-the-art methods and provides high prediction accuracy (i.e., 97.70%) with low false alarm using EEG signals in different brain locations from a benchmark data set.Keywords: Epilepsy, seizure, phase correlation, fluctuation, deviation.
Procedia PDF Downloads 4671110 Quantification of Dispersion Effects in Arterial Spin Labelling Perfusion MRI
Authors: Rutej R. Mehta, Michael A. Chappell
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Introduction: Arterial spin labelling (ASL) is an increasingly popular perfusion MRI technique, in which arterial blood water is magnetically labelled in the neck before flowing into the brain, providing a non-invasive measure of cerebral blood flow (CBF). The accuracy of ASL CBF measurements, however, is hampered by dispersion effects; the distortion of the ASL labelled bolus during its transit through the vasculature. In spite of this, the current recommended implementation of ASL – the white paper (Alsop et al., MRM, 73.1 (2015): 102-116) – does not account for dispersion, which leads to the introduction of errors in CBF. Given that the transport time from the labelling region to the tissue – the arterial transit time (ATT) – depends on the region of the brain and the condition of the patient, it is likely that these errors will also vary with the ATT. In this study, various dispersion models are assessed in comparison with the white paper (WP) formula for CBF quantification, enabling the errors introduced by the WP to be quantified. Additionally, this study examines the relationship between the errors associated with the WP and the ATT – and how this is influenced by dispersion. Methods: Data were simulated using the standard model for pseudo-continuous ASL, along with various dispersion models, and then quantified using the formula in the WP. The ATT was varied from 0.5s-1.3s, and the errors associated with noise artefacts were computed in order to define the concept of significant error. The instantaneous slope of the error was also computed as an indicator of the sensitivity of the error with fluctuations in ATT. Finally, a regression analysis was performed to obtain the mean error against ATT. Results: An error of 20.9% was found to be comparable to that introduced by typical measurement noise. The WP formula was shown to introduce errors exceeding 20.9% for ATTs beyond 1.25s even when dispersion effects were ignored. Using a Gaussian dispersion model, a mean error of 16% was introduced by using the WP, and a dispersion threshold of σ=0.6 was determined, beyond which the error was found to increase considerably with ATT. The mean error ranged from 44.5% to 73.5% when other physiologically plausible dispersion models were implemented, and the instantaneous slope varied from 35 to 75 as dispersion levels were varied. Conclusion: It has been shown that the WP quantification formula holds only within an ATT window of 0.5 to 1.25s, and that this window gets narrower as dispersion occurs. Provided that the dispersion levels fall below the threshold evaluated in this study, however, the WP can measure CBF with reasonable accuracy if dispersion is correctly modelled by the Gaussian model. However, substantial errors were observed with other common models for dispersion with dispersion levels similar to those that have been observed in literature.Keywords: arterial spin labelling, dispersion, MRI, perfusion
Procedia PDF Downloads 3701109 The Iconic Pink Donut Box: An Analysis of Memory and Identity Amongst Cambodian Refugees in California
Authors: Basmah Arshad
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In the aftermath of the Cambodian genocide, many refugees resettled in America. They carved out a distinctively Cambodian-American space in California with donut shops, establishing a tight-knit community that worked to achieve ‘the American dream’. Urged by traumatic memories of the genocide and American society directly encouraging (if not demanding) cultural assimilation, these refugees and successive generations continuously worked to re-identify themselves as Americans. Artist Phung Huynh grew up in this context of family-owned donut shops and the frantic scramble for stability and security. It is this community that she depicts in her artwork series from the late 2010s, ‘Khmerican: Drawing on Pink Donut Boxes’. Huynh's artwork challenges dominant Western narratives about the Cambodian genocide by pushing forward images of resilience, resistance, and joy, while also allowing for a discussion about issues of assimilation, identity, and nostalgia in the Cambodian-American community. It also provokes deeply relevant questions about how refugees and immigrants deliberately appropriate elements of the Americana (eg, donuts) to assimilate and re-fashion their identity as a tactic for financial stability and social survival.Keywords: Cambodian diaspora, cultural identity, assimilation, food, artwork
Procedia PDF Downloads 651108 Targeting APP IRE mRNA to Combat Amyloid -β Protein Expression in Alzheimer’s Disease
Authors: Mateen A Khan, Taj Mohammad, Md. Imtaiyaz Hassan
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Alzheimer’s disease is characterized by the accumulation of the processing products of the amyloid beta peptide cleaved by amyloid precursor protein (APP). Iron increases the synthesis of amyloid beta peptides, which is why iron is present in Alzheimer's disease patients' amyloid plaques. Iron misregulation in the brain is linked to the overexpression of APP protein, which is directly related to amyloid-β aggregation in Alzheimer’s disease. The APP 5'-UTR region encodes a functional iron-responsive element (IRE) stem-loop that represents a potential target for modulating amyloid production. Targeted regulation of APP gene expression through the modulation of 5’-UTR sequence function represents a novel approach for the potential treatment of AD because altering APP translation can be used to improve both the protective brain iron balance and provide anti-amyloid efficacy. The molecular docking analysis of APP IRE RNA with eukaryotic translation initiation factors yields several models exhibiting substantial binding affinity. The finding revealed that the interaction involved a set of functionally active residues within the binding sites of eIF4F. Notably, APP IRE RNA and eIF4F interaction were stabilized by multiple hydrogen bonds with residues of APP IRE RNA and eIF4F. It was evident that APP IRE RNA exhibited a structural complementarity that tightly fit within binding pockets of eIF4F. The simulation studies further revealed the stability of the complexes formed between RNA and eIF4F, which is crucial for assessing the strength of these interactions and subsequent roles in the pathophysiology of Alzheimer’s disease. In addition, MD simulations would capture conformational changes in the IRE RNA and protein molecules during their interactions, illustrating the mechanism of interaction, conformational change, and unbinding events and how it may affect aggregation propensity and subsequent therapeutic implications. Our binding studies correlated well with the translation efficiency of APP mRNA. Overall, the outcome of this study suggests that the genomic modification and/or inhibiting the expression of amyloid protein by targeting APP IRE RNA can be a viable strategy to identify potential therapeutic targets for AD and subsequently be exploited for developing novel therapeutic approaches.Keywords: Alzheimer's disease, Protein-RNA interaction analysis, molecular docking simulations, conformational dynamics, binding stability, binding kinetics, protein synthesis.
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