Search results for: inflammatory hypothesis of psychosis

Authors: Deepak Mohan, Sushma Sharma

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Diclofenac sodium, a member of the acetic acid family of non-steroidal anti-inflammatory drugs, is used to retard inflammation, arthritis pain and ankylosing spondylitis. The drug is known to cause severe injury in different tissues due to formation of reactive oxygen species. The present study is focused on the effect of different doses of diclofenac (4 mg/kg/body weight and 14 mg/kg/body weight on histoarchitecture of the liver from 7-28 days of the investigation. Diclofenac administration resulted in distorted hepatic degeneration and formation of wide areas in the form of sinusoidal gaps. Hepatic fibrosis noticed in different stages of investigation could be attributed to chronic inflammation and reactive oxygen species which results in deposition of extracellular matrix proteins. The abrupt degenerative changes observed during later stages of the experiment showed maximum damage to the liver, and there was enlargement of sinusoidal gaps accompanied by maximum necrosis in the tissues.

Keywords: arthritis, diclofenac, histoarchitecture, sinusoidal

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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

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Authors: Ali Asghar Saki, Sayed Ali Hosseini Siyar, Abbass Ashoori

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This study was conducted to evaluate the effect of Echinacea purpurea on the expression of cyclooxygenase-2 (COX-2), interleukin-17F (IL-17F) in seven-day-old broiler chickens. Four groups were fed with concentration of 0 g/kg, 5 g/kg, 10 g/kg and 20 g/kg from the root of E. purpurea in the basal diet and two other groups were only fed with the basal diet for 21 days. At the 28^th day, lipopolysaccharide (LPS, 2 mg/kg diet) was injected in four groups and the basal diet group was injected by saline as control. The chickens’ spleen RNA expression was measured for the COX-2 and IL-17F genes by Real-Time PCR. The results have shown that chickens which were fed E. purpurea had a lower COX-2 and IL-17F mRNA expression. The chickens who have received LPS only, lymphocyte was lower than other treatments. Vital organ weights were not significantly different, but body weight loss was recovered by dietary herbs inclusion. The results of this study have shown the positive effect of an anti-inflammatory herb to prevent the undesirable effect of inflammation.

Keywords: broiler chickens, Echinacea purporea, gene expression, lipopolysaccharide

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Authors: Gracie Tredget, Raymond McGrath, Karen Ang, Julie Williams, Nick Sevdalis, Fiona Gaughran, Jorge Aria de la Torre, Ioannis Bakolis, Andy Healey, Zarnie Khadjesari, Euan Sadler, Natalia Stepan

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Background: Preventable physical health problems have been found to increase morbidity rates amongst adults living with serious mental illness (SMI). Community mental health clinicians have a role in identifying, and preventing physical health problems worsening, and supporting primary care services to administer routine physical health checks for their patients. However, little is known about how mental health staff perceive and approach their role when providing physical healthcare amongst patients with SMI, or the impact these attitudes have on routine practice. Methods: The present study involves a prospective service evaluation specific to Adult Community Mental Health Services at South London and Maudsley NHS Foundation Trust (SLaM). A qualitative methodology will use semi-structured interviews, focus groups and observations to explore attitudes, perceptions and experiences of staff, patients, and carers (n=64) towards physical healthcare, and barriers or facilitators that impact upon it. 1South London and Maudsley NHS Foundation Trust, London, SE5 8AZ, UK 2 Centre for Implementation Science, King’s College London, London, SE5 8AF, UK 3 Psychosis Studies, King's College London, London, SE5 8AF, UK 4 Department of Biostatistics and Health Informatics, King’s College London, London, SE5 8AF, UK 5 Kings Health Economics, King's College London, London, SE5 8AF, UK 6 Behavioural and Implementation Science (BIS) research group, University of East Anglia, Norwich, UK 7 Department of Nursing, Midwifery and Health, University of Southampton, Southampton, UK 8 Mind and Body Programme, King’s Health Partners, Guy’s Hospital, London, SE1 9RT *[email protected] Analysis: Data from across qualitative tasks will be synthesised using Framework Analysis methodologies. Staff, patients, and carers will be invited to participate in co-development of recommendations that can improve routine physical healthcare within Adult Community Mental Health Teams at SLaM. Results: Data collection is underway at present. At the time of the conference, early findings will be available to discuss. Conclusions: An integrated approach to mind and body care is needed to reduce preventable deaths amongst people with SMI. This evaluation will seek to provide a framework that better equips staff to approach physical healthcare within a mental health setting.

Keywords: severe mental illness, physical healthcare, adult community mental health, nursing

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Authors: Azza A. Ali, Asmaa Abdelaty, Mona G. Khalil, Mona M. Kamal, Karema Abu-Elfotuh

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Background: Aluminium (Al) is known as a neurotoxin environmental pollutant that can cause certain diseases as Dementia, Alzheimer's disease, and Parkinsonism. It is widely used in antacid drugs as well as in food additives and toothpaste. Stresses have been linked to cognitive impairment; Social isolation (SI) may exacerbate memory deficits while protein malnutrition (PM) increases oxidative damage in cortex, hippocampus and cerebellum. The risk of cognitive decline may be lower by maintaining social connections. Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea and has antioxidant, anti-inflammatory and anti-atherogenic effects as well as health-promoting effects in CNS. Objective: To study the influence of different stressful conditions as social isolation, electric shock (EC) and inadequate Nutritional condition as PM on neurotoxicity induced by Al in rats as well as to investigate the possible protective effect of EGCG in these stressful and PM conditions. Methods: Rats were divided into two major groups; protected group which was daily treated during three weeks of the experiment by EGCG (10 mg/kg, IP) or non-treated. Protected and non-protected groups included five subgroups as following: One normal control received saline and four Al toxicity groups injected daily for three weeks by ALCl3 (70 mg/kg, IP). One of them served as Al toxicity model, two groups subjected to different stresses either by isolation as mild stressful condition (SI-associated Al toxicity model) or by electric shock as high stressful condition (EC- associated Al toxicity model). The last was maintained on 10% casein diet (PM -associated Al toxicity model). Isolated rats were housed individually in cages covered with black plastic. Biochemical changes in the brain as acetyl cholinesterase (ACHE), Aβ, brain derived neurotrophic factor (BDNF), inflammatory mediators (TNF-α, IL-1β), oxidative parameters (MDA, SOD, TAC) were estimated for all groups. Histopathological changes in different brain regions were also evaluated. Results: Rats exposed to Al for three weeks showed brain neurotoxicity and neuronal degenerations. Both mild (SI) and high (EC) stressful conditions as well as inadequate nutrition (PM) enhanced Al-induced neurotoxicity and brain neuronal degenerations; the enhancement induced by stresses especially in its higher conditions (ES) was more pronounced than that of inadequate nutritional conditions (PM) as indicated by the significant increase in Aβ, ACHE, MDA, TNF-α, IL-1β together with the significant decrease in SOD, TAC, BDNF. On the other hand, EGCG showed more pronounced protection against hazards of Al in both stressful conditions (SI and EC) rather than in PM .The protective effects of EGCG were indicated by the significant decrease in Aβ, ACHE, MDA, TNF-α, IL-1β together with the increase in SOD, TAC, BDNF and confirmed by brain histopathological examinations. Conclusion: Neurotoxicity and brain neuronal degenerations induced by Al were more severe with stresses than with PM. EGCG can protect against Al-induced brain neuronal degenerations in all conditions. Consequently, administration of EGCG together with socialization as well as adequate protein nutrition is advised especially on excessive Al-exposure to avoid the severity of its neuronal toxicity.

Keywords: environmental pollution, aluminum, social isolation, protein malnutrition, neuronal degeneration, epigallocatechin-3-gallate, rats

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Authors: Rory Austin Clark

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This primary research represents an ongoing two year inductive mixed-methods project endeavouring to unravel the subjective reality of hyperconnected young adults in Western societies who have come of age with social media and smartphones. It is to be presented as well as analyzed and contextualized through a written master’s thesis as well as a documentary/mockumentary meshed with a Web 2.0 app providing the capacity for prosumer, 'audience 2.0' functionality. The media component seeks to explore not only thematic issues via real-life research interviews and fictional narrative but technical issues within the format relating to the quest for intimate, authentic connection as well as compelling dissemination of scholarly knowledge in an age of ubiquitous personalized daily digital media creation and consumption. The overarching hypothesis is that the aforementioned individuals process and make sense of their world, find shared meaning, and formulate notions-of-self in ways drastically different than pre-2007 via hyper-mediation-of-self and surroundings. In this pursuit, research questions have progressed from examining how young adult digital natives understand their use of social media to notions relating to the potential functionality of Web 2.0 for prosocial and altruistic engagement, on and offline, through the eyes of these individuals no longer understood as simply digital natives, but social media natives, and at the conclusion of that phase of research, as 'neoliberalized social media natives' (NSMN). This represents the two most potent macro factors in the paradigmatic shift in NSMS’s worldview, that they are not just children of social media, but of the palpable shift to neoliberal ways of thinking and being in the western socio-cultures since the 1980s, two phenomena that have a reflexive æffective relationship on their perception of figure and ground. This phase also resulted in the working hypothesis of 'social media comparison anxiety' and a nascent understanding of NSMN’s habitus and habitation in a subjective reality of fully converged online/offline worlds, where any phenomena originating in one realm in some way are, or at the very least can be, re-presented or have effect in the other—creating hyperreal reception. This might also be understood through a 'society as symbolic cyborg model', in which individuals have a 'digital essence'-- the entirety of online content that references a single person, as an auric living, breathing cathedral, museum, gallery, and archive of self of infinite permutations and rhizomatic entry and exit points.

Keywords: affect, hyperreal, neoliberalism, postmodernism, social media native, subjective reality, Web 2.0

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Authors: Sh. Mirhosseini, Y. Haghighatfar, M. Sedighi

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Forced vibration problem of a delaminated beam made of fiber metal laminates is studied in this paper. Firstly, a delamination is considered to divide the beam into four sections. The classic beam theory is assumed to dominate each section. The layers on two sides of the delamination are constrained to have the same deflection. This hypothesis approves the conditions of compatibility as well. Consequently, dynamic response of the beam is obtained by the means of differential transform method (DTM). In order to verify the correctness of the results, a model is constructed using commercial software ABAQUS 6.14. A linear spring with constant stiffness takes the effect of contact between delaminated layers into account. The attained semi-analytical outcomes are in great agreement with finite element analysis.

Keywords: delamination, forced vibration, finite element modelling, natural frequency

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Authors: Z. Chekini, P. Afsharian, F. Ramezanali, A. A. Akhlaghi, R. Aflatoonian

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Macrophage migration inhibitory factor (MIF) is a key pro-inflammatory cytokine that involves in pathophysiological events of endometriosis. We aimed to evaluate the association between mRNA expression levels and polymorphisms of MIF in endometriosis. Seventy endometriosis patients and 70 volunteer fertile women were recruited. RFLP was applied to determine -173G/C polymorphism. ORF polymorphisms and -794(CATT)5-8 were detected by sequencing. Q-PCR was used for expression study of 14 ectopic tissues of patients. Homozygote of CATT5 was observed only in controls. The CATT5/G haplotype related to controls (p=0.094, OR=0.61). Expression level of MIF with -794(CATT)6,7/-173GC was significantly more than the other haplotypes (p=0.00). We identified four SNPs including: +254rs2096525 (p=0.843), +626rs33958703 (p=0.029), +656rs2070766 (p=0.703) and +509rs182012324 (p=1.00). In conclusion, increased repeat of CATT and presence of C allele in promoter of MIF were significantly associated with mRNA level in patients. It seems that +509rs182012324 and +626rs33958703 SNPs were significantly correlated with susceptibility to endometriosis.

Keywords: endometriosis, haplotype, macrophage migration inhibitory factor, polymorphism

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Authors: Akanksha Agrawal, Richa Rathor, Geetha Suryakumar

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Muscle represents about ¾ of the body mass, and a healthy muscular system is required for human performance. A healthy muscular system is dynamically balanced via the catabolic and anabolic process. High altitude associated hypoxia altered this redox balance via producing reactive oxygen and nitrogen species that ultimately modulates protein structure and function, hence, disrupts proteostasis or protein homeostasis. The mechanism by which proteostasis is clinched includes regulated protein translation, protein folding, and protein degradation machinery. Perturbation in any of these mechanisms could increase proteome imbalance in the cellular processes. Altered proteostasis in skeletal muscle is likely to be responsible for contributing muscular atrophy in response to hypoxia. Therefore, we planned to elucidate the mechanism involving altered proteostasis leading to skeletal muscle atrophy under chronic hypobaric hypoxia. Material and Methods-Male Sprague Dawley rats weighing about 200-220 were divided into five groups - Control (Normoxic animals), 1d, 3d, 7d and 14d hypobaric hypoxia exposed animals. The animals were exposed to simulated hypoxia equivalent to 282 torr pressure (equivalent to an altitude of 7620m, 8% oxygen) at 25°C. On completion of chronic hypobaric hypoxia (CHH) exposure, rats were sacrificed, muscle was excised and biochemical, histopathological and protein synthesis signaling were studied. Results-A number of changes were observed with the CHH exposure time period. ROS was increased significantly on 07 and 14 days which were attributed to protein oxidation via damaging muscle protein structure by oxidation of amino acids moiety. The oxidative damage to the protein further enhanced the various protein degradation pathways. Calcium activated cysteine proteases and other intracellular proteases participate in protein turnover in muscles. Therefore, we analysed calpain and 20S proteosome activity which were noticeably increased at CHH exposure as compared to control group representing enhanced muscle protein catabolism. Since inflammatory markers (myokines) affect protein synthesis and triggers degradation machinery. So, we determined inflammatory pathway regulated under hypoxic environment. Other striking finding of the study was upregulation of Akt/PKB translational machinery that was increased on CHH exposure. Akt, p-Akt, p70 S6kinase, and GSK- 3β expression were upregulated till 7d of CHH exposure. Apoptosis related markers, caspase-3, caspase-9 and annexin V was also increased on CHH exposure. Conclusion: The present study provides evidence of disrupted proteostasis under chronic hypobaric hypoxia. A profound loss of muscle mass is accompanied by the muscle damage leading to apoptosis and cell death under CHH. These cellular stress response pathways may play a pivotal role in hypobaric hypoxia induced skeletal muscle atrophy. Further research in these signaling pathways will lead to development of therapeutic interventions for amelioration of hypoxia induced muscle atrophy.

Keywords: Akt/PKB translational machinery, chronic hypobaric hypoxia, muscle atrophy, protein degradation

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Authors: Sandy Elsayed, Aya Mohamed, Noha Nassar

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Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behavior. Multiple studies suggest that oxidative stress and neuroinflammation are key factors in the etiology of ASD and often associated with worsening of ASD-related behaviors. Nuclear factor erythroid 2-related factor 2 (NRF-2) is a transcription factor that promotes expression of antioxidant response element genes in oxidative stress. In ASD subjects, decreased expression of NRF-2 in frontal cortex shifted the redox homeostasis towards oxidative stress, and resulted in inflammation evidenced by elevation of nuclear factor kappa B (NF-κB) transcriptional activity. Dimethyl fumarate (DMF) is a NRF-2 activator that is used in the treatment of psoriasis and multiple sclerosis. It participates in the transcriptional control of inflammatory factors via inhibition of NF-κB and its downstream targets. This study aimed to investigate the role of DMF in alleviating the cognitive impairments and behavior deficits associated with ASD through mitigation of oxidative stress and inflammation in prenatal valproic acid (VPA) rat model of autism. Methods: Pregnant female Wistar rats received a single intraperitoneal injection of VPA (600 mg/kg) to induce autistic-like-behavioral and neurobiological alterations in their offspring. Chronic oral gavage of DMF (150mg/kg/day) started from postnatal day (PND) 24 till PND62 (39 days). Prenatal VPA exposure elicited autistic behaviors including decreased social interaction and stereotyped behavior. Social interaction was evaluated using three-chamber sociability test and calculation of sociability index (SI), while stereotyped repetitive behavior and anxiety associated with ASD were assessed using marble burying test (MBT). Biochemical analyses were done on prefrontal cortex homogenates including NRF-2, and NF-κB expression. Moreover, inducible nitric oxide synthase (iNOS) gene expression and tumor necrosis factor (TNF-) protein expression were evaluated as markers of inflammation. Results: Prenatal VPA elicited decreased social interaction shown by decreased SI compared to control group (p < 0.001) and DMF enhanced SI (p < 0.05). In MBT, prenatal injection of VPA manifested stereotyped behavior and enhanced number of buried marbles compared to control (p < 0.05) and DMF reduced the anxiety-related behavior in rats exhibiting ASD-like behaviors (p < 0.05). In prefrontal cortex, NRF-2 expression was downregulated in prenatal VPA model (p < 0.0001) and DMF reversed this effect (p < 0.0001). The inflammatory transcription factor NF-κB was elevated in prenatal VPA model (p < 0.0001) and reduced (p < 0.0001) upon NRF-2 activation by DMF. Prenatal VPA expressed higher levels of proinflammatory cytokine TNF- compared to control group (p < 0.0001) and DMF reduced it (p < 0.0001). Finally, the gene expression of iNOS was downregulated upon NRF-2 activation by DMF (p < 0.01). Conclusion: This study proposes that DMF is a potential agent that can be used to ameliorate autistic-like-changes through NRF-2 activation along with NF-κB downregulation and therefore, it is a promising novel therapy for ASD.

Keywords: autism spectrum disorders, dimethyl fumarate, neuroinflammation, NRF-2

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Authors: S. Khoshemehry, M. J. Pourvaghar

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Inflammatory markers are known as the main predictors of cardiovascular diseases. This study aimed at determining the effect of 8 weeks of interval endurance training on hs-CRP level and some anthropometric parameters in overweight men. Following the call for participation in research project in Kashan, 73 volunteers participated in it and constituted the statistical population of the study. Then, 28 overweight young men from the age of 22 to 25 years old were randomly assigned into two groups of experimental and control group (n=14). Anthropometric and the blood sample was collected before and after the termination of the program for measuring hs-CRP. The interval endurance program was performed at 60 to 75% of maximum heart rate in 2 sessions per week for 8 weeks. Kolmogorov-Smirnov test was used to test whether two samples come from the same distribution and T-test was used to assess the difference of two groups which were statistically significant at the level of 0.05. The result indicated that there was a significant difference between the hs-RP, weight, BMI and W/H ratio of overweight men in posttest in the exercise group (P≤0.05) but not in the control group. Interval endurance training program causes decrease in hs-CRP level and anthropometric parameters.

Keywords: interval endurance training program, HS-CRP, overweight, anthropometric

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Authors: Marcela Dvorakova, Lenka Langhansova, Premysl Landa

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A series of quinazoline derivatives bearing aromatic rings in 2- and 4-positions were prepared and tested for their biological activity. Firstly, the compounds were evaluated for their potential to inhibit various kinases, such as autophagy activating kinase ULK1, 3-Phosphoinositide-dependent kinase 1, and TANK-binding kinase 1. None of the compounds displayed any activity on these kinases. Secondly, the compounds were tested for their anti-inflammatory activity expressed as cyclooxygenase (COX) isoforms and 5-lipoxygenase (5-LOX) inhibition. Three of the compounds showed significant selectivity towards COX-1 isoform (COX-2/COX-1 SI = 20-30). They inhibited COX-1 in a single-digit µM range. There was also one compound that exhibited inhibitory activity towards all three tested enzymes in µM range (IC50COX-1 = 1.9 µM; IC50COX-2 and 5-LOX = 10.1µM. COX-1 inhibition was until recently considered undesirable due to COX-1 constitutive expression in most cell types and tissues. Thus, there are not many compounds known with selective COX-1 activity. However, it is now believed that COX-1 plays an important role in the pathophysiology of several acute and chronic disorders, including cancer or neurodegenerative diseases. Thus, the discovery of effective COX-1 selective inhibitors is desirable and important.

Keywords: cyclooxygenases, kinases, lipoxygenases, quinazolines

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Authors: A. Hilsana, Vinay U. Rao, M. Sudhakar

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Even though a number of non-steroidal anti-inflammatory drugs (NSAIDS) are available with different chemistries, they share a common solubility characteristic that is they are relatively more soluble in alkaline environment and practically insoluble in acidic environment. This work deals with developing a wax matrix drug delivery platform for controlled delivery of three model NSAIDS, Diclofenac sodium (DNa), Mefenamic acid (MA) and Naproxen (NPX) using the melt granulation technique. The aim of developing the platform was to have a general understanding on how an erodible matrix system modulates drug delivery rate and extent and how it can be optimized to give a delivery system which shall release the drug as per a common target product profile (TPP). Commonly used waxes like Cetostearyl alcohol and stearic acid were used singly an in combination to achieve a TPP of not 15 to 35% in 1 hour and not less than 80% Q in 24 hours. Full factorial design of experiments was followed for optimization of the formulation.

Keywords: NSAIDs, controlled delivery, target product profile, melt granulation

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Authors: Romany Wagih Farag Zaky

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The relationship between development and human rights has long been the subject of academic debate. To understand the dynamics between these two concepts, various principles are adopted, from the right to development to development-based human rights. Despite the initiatives taken, the relationship between development and human rights remains unclear. However, the overlap between these two views and the idea that efforts should be made in the field of human rights have increased in recent years. It is then evaluated whether the right to sustainable development is acceptable or not. The article concludes that the principles of sustainable development are directly or indirectly recognized in various human rights instruments, which is a good answer to the question posed above. This book therefore cites regional and international human rights agreements such as , as well as the jurisprudence and interpretative guidelines of human rights institutions, to prove this hypothesis.

Keywords: sustainable development, human rights, the right to development, the human rights-based approach to development, environmental rights, economic development, social sustainability human rights protection, human rights violations, workers’ rights, justice, security

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Authors: Wanvipa Thongborisute, Punyaphat Sirithanabadeekul, Pichit Suvanprakorn, Anan Jiraviroon

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Background: Acne vulgaris is one of the most common dermatologic problems, and can have a significant psychological and physical effect on patients. Propionibacterium acnes' roles in acne vulgaris involve the activation of toll-like receptor 4 (TLR4), and toll-like receptor 2 (TLR2) pathways. By activating these pathways, inflammatory events of acne lesions, comedogenesis and sebaceous lipogenesis can occur. Currently, there are several topical agents commonly use in treating acne vulgaris that are known to have an effect on TLRs, such as retinoic acid and adapalene, but these drugs still have some irritating effects. At present, there is an alarming increase in rate of bacterial resistance due to irrational used of antibiotics both orally and topically. For this reason, acne treatments should contain bioactive molecules targeting at the site of action for the most effective therapeutic effect with the least side effects. Sparganium stoloniferumis a Chinese aquatic herb containing a compound called Sparstolonin B (SsnB), which has been reported to selectively blocks Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4)-mediated inflammatory signals. Therefore, this topical TLR2 and TLR4 antagonist, in a form of Sparganium stoloniferum-derived compound containing SsnB, should give a benefit in reducing inflammation of acne vulgaris lesions and providing an alternative treatments for patients with this condition. Materials and Methods: The objectives of this randomized double blinded split faced placebo controlled trial is to study the safety and efficacy of the Sparganium stoloniferum-derived compound. 32 volunteered patients with mild to moderate degree of acne vulgaris according to global acne grading system were included in the study. After being informed and consented the subjects were given 2 topical treatments for acne vulgaris, one being topical 2.40% Sparganium stoloniferum extraction (containing Sparstolonin B) and the other, placebo. The subjects were asked to apply each treatment to either half of the face daily morning and night by randomization for 8 weeks, and come in for a weekly follow up. For each visit, the patients went through a procedure of lesion counting, including comedones, papules, nodules, pustules, and cystic lesions. Results: During 8 weeks of experimentation, the result shows a reduction in total lesions number between the placebo and the treatment side show statistical significance starting at week 4, where the 95% confidence interval begin to no longer overlap, and shows a trend of continuing to be further apart. The decrease in the amount of total lesions between week 0 and week 8 of the placebo side shows no statistical significant at P value >0.05. While the decrease in the amount of total lesions of acne vulgaris of the treatment side comparing between week 0 and week 8 shows statistical significant at P value <0.001. Conclusion: The data demonstrates that 2.40% Sparganium stoloniferum extraction (containing Sparstolonin B) is more effective in treating acne vulgaris comparing to topical placebo in treating acne vulgaris, by showing significant reduction in the total numbers of acne lesions. Therefore, this topical Sparganium stoloniferum extraction could become a potential alternative treatment for acne vulgaris.

Keywords: acne vulgaris, sparganium stoloniferum, sparstolonin B, toll-like receptor 2, toll-like receptor 4

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Authors: Behnaz Farahani, Abbas Mirzaei

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This study explores association between circadian rhythm pattern and some demographic incidences. The participants targeting 193 (97 females and 96 males between the ages of 20-30 years) Iranian bachelor students from Islamic Azad University who completed the self-reported over the 2nd semester 2011-2012 university year. The questionnaire has been tailored amalgamation of Horn & Östberg Questionnaire (MEQ) and Demographic Incidences Questionnaire in order to measure the students circadian rhythm pattern and their Demographic Incidences. The finding of this quantitative, descriptive, cross-sectional analysis confirmed the hypothesis in that 'circadian rhythm pattern' was positively associated with the demographic indices like age, marital status, gender, day in week and month of the birth time, and parent’s age and educational level at the time of the birth of the samples.

Keywords: circadian rhythm pattern, demographic incidences, morning type, evening type

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Authors: Szymon Rutkowski, Tomasz Korbak

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We present a reinforcement-learning-based method of training neural machine translation models without parallel corpora. The standard encoder-decoder approach to machine translation suffers from two problems we aim to address. First, it needs parallel corpora, which are scarce, especially for low-resource languages. Second, it lacks psychological plausibility of learning procedure: learning a foreign language is about learning to communicate useful information, not merely learning to transduce from one language’s 'encoding' to another. We instead pose the problem of learning to translate as learning a policy in a communication game between two agents: the translator and the classifier. The classifier is trained beforehand on a natural language inference task (determining the entailment relation between a premise and a hypothesis) in the target language. The translator produces a sequence of actions that correspond to generating translations of both the hypothesis and premise, which are then passed to the classifier. The translator is rewarded for classifier’s performance on determining entailment between sentences translated by the translator to disciple’s native language. Translator’s performance thus reflects its ability to communicate useful information to the classifier. In effect, we train a machine translation model without the need for parallel corpora altogether. While similar reinforcement learning formulations for zero-shot translation were proposed before, there is a number of improvements we introduce. While prior research aimed at grounding the translation task in the physical world by evaluating agents on an image captioning task, we found that using a linguistic task is more sample-efficient. Natural language inference (also known as recognizing textual entailment) captures semantic properties of sentence pairs that are poorly correlated with semantic similarity, thus enforcing basic understanding of the role played by compositionality. It has been shown that models trained recognizing textual entailment produce high-quality general-purpose sentence embeddings transferrable to other tasks. We use stanford natural language inference (SNLI) dataset as well as its analogous datasets for French (XNLI) and Polish (CDSCorpus). Textual entailment corpora can be obtained relatively easily for any language, which makes our approach more extensible to low-resource languages than traditional approaches based on parallel corpora. We evaluated a number of reinforcement learning algorithms (including policy gradients and actor-critic) to solve the problem of translator’s policy optimization and found that our attempts yield some promising improvements over previous approaches to reinforcement-learning based zero-shot machine translation.

Keywords: agent-based language learning, low-resource translation, natural language inference, neural machine translation, reinforcement learning

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Authors: Nadia Fatima Zahra Malki

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The aim of the study is to show the role of total Quality Management on firm performance, research relied on the views of a sample managers working in the Marinel pharmaceutical company. The research aims to achieve many objectives, including increasing awareness of the concepts of Total Quality Management on Firm Performance, especially in the manufacturing firm, providing a future vision of the possibility of success, and the actual application of the Principles of Total Quality Management in the manufacturing company. The research adopted a default model was built after a review and analysis of the literature review in the context of one hypothesis's main points at the origin of a group of sub-hypotheses. The research presented a set of conclusions, and the most important of these conclusions was that there is a relationship between the Principles of TQM and Firm Performance.

Keywords: total quality management, competitive advantage, companies, objectives

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Authors: Giovanni Incerti

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In this paper the dynamic behavior of a synchronous belt drive during start-up is analyzed and discussed. Besides considering the belt elasticity, the mathematical model here proposed also takes into consideration the electrical behaviour of the DC motor. The solution of the motion equations is obtained by means of the modal analysis in state space, which allows to obtain the decoupling of all equations of the mathematical model without introducing the hypothesis of proportional damping. The mathematical model of the transmission and the solution algorithms have been implemented within a computing software that allows the user to simulate the dynamics of the system and to evaluate the effects due to the elasticity of the belt branches and to the electromagnetic behavior of the DC motor. In order to show the details of the calculation procedure, the paper presents a case study developed with the aid of the abovementioned software.

Keywords: belt drive, vibrations, startup, DC motor

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Authors: Libena Cernohorska, Jan Cernohorsky

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This article aims to evaluate the impact of loans provided within the Czech banking sector on the growth of the Czech economy. The article is based on research of current scientific findings in respect to bank loans and economic development. The paper is based on data taken from the Czech Statistical Office on the development of the gross domestic product and data from the Czech National Bank on the development of loans from the period 2004-2015. Links between selected variables are tested using Granger causality tests. The results calculated confirm the hypothesis of the impact of the loans on economic growth, with a six-month delay. The results thus correspond to the standard economic findings and results of most previous studies.

Keywords: bank, business cycle, economic growth, loans

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Authors: Faruk Emir, Simel Ayyıldız, Cem Şahin

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Behçet’s disease or Behçet’s syndrome is a chronic and multi-systemic inflammatory disease of unknown cause. This syndrome often presents with mucous membrane ulceration and ocular problems. As a systemic disease Behcet includes triple-symptom complex of recurrent oral aphthous ulcers, genital ulcers, and uveitis. Nearly all patients present with some form of painful oral mucocutaneous ulcerations in the form of aphthous ulcers. The aim of the treatment plan for Behçet’s Disease patients is to eliminate oral problems and increase the patient comfort.This clinical report represents the prosthodontic rehabilitation of Behcet’s disease patients mandibular total edentulism with the use of implant supported prosthesis that planned on custom abutments and bar retainers via CAD/CAM technology and patient satisfaction has been achieved in function and aesthetics.

Keywords: Behçet’s disease, CAD/CAM, custom-made manufacturing, titanium milled bar retainer

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Authors: M. Qamarul Islam, Ergun Dogan, Mehmet Yazici

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There is a growing body of evidence that non-normal data is more prevalent in nature than the normal one. Examples can be quoted from, but not restricted to, the areas of Economics, Finance and Actuarial Science. The non-normality considered here is expressed in terms of fat-tailedness and asymmetry of the relevant distribution. In this study a skew t distribution that can be used to model a data that exhibit inherent non-normal behavior is considered. This distribution has tails fatter than a normal distribution and it also exhibits skewness. Although maximum likelihood estimates can be obtained by solving iteratively the likelihood equations that are non-linear in form, this can be problematic in terms of convergence and in many other respects as well. Therefore, it is preferred to use the method of modified maximum likelihood in which the likelihood estimates are derived by expressing the intractable non-linear likelihood equations in terms of standardized ordered variates and replacing the intractable terms by their linear approximations obtained from the first two terms of a Taylor series expansion about the quantiles of the distribution. These estimates, called modified maximum likelihood estimates, are obtained in closed form. Hence, they are easy to compute and to manipulate analytically. In fact the modified maximum likelihood estimates are equivalent to maximum likelihood estimates, asymptotically. Even in small samples the modified maximum likelihood estimates are found to be approximately the same as maximum likelihood estimates that are obtained iteratively. It is shown in this study that the modified maximum likelihood estimates are not only unbiased but substantially more efficient than the commonly used moment estimates or the least square estimates that are known to be biased and inefficient in such cases. Furthermore, in conventional regression analysis, it is assumed that the error terms are distributed normally and, hence, the well-known least square method is considered to be a suitable and preferred method for making the relevant statistical inferences. However, a number of empirical researches have shown that non-normal errors are more prevalent. Even transforming and/or filtering techniques may not produce normally distributed residuals. Here, a study is done for multiple linear regression models with random error having non-normal pattern. Through an extensive simulation it is shown that the modified maximum likelihood estimates of regression parameters are plausibly robust to the distributional assumptions and to various data anomalies as compared to the widely used least square estimates. Relevant tests of hypothesis are developed and are explored for desirable properties in terms of their size and power. The tests based upon modified maximum likelihood estimates are found to be substantially more powerful than the tests based upon least square estimates. Several examples are provided from the areas of Economics and Finance where such distributions are interpretable in terms of efficient market hypothesis with respect to asset pricing, portfolio selection, risk measurement and capital allocation, etc.

Keywords: least square estimates, linear regression, maximum likelihood estimates, modified maximum likelihood method, non-normality, robustness

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Authors: Shrestha Sharma, Jasjeet K. Sahni, Javed Ali, Sanjula Baboota

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Introduction: Rutin is a naturally occurring strong antioxidant molecule belonging to bioflavonoid category. Due to its free radical scavenging properties, it has been found to be beneficial in the treatment of various diseases including inflammation, cancer, diabetes, allergy, cardiovascular disorders and various types of microbial infections. Despite its beneficial effects, it suffers from the problem of low aqueous solubility which is responsible for low oral bioavailability. The aim of our study was to optimize and characterize self-nanoemulsifying drug delivery system (SNEDDS) of rutin using Box-Behnken design (BBD) combined with a desirability function. Further various antioxidant, pharmacokinetic and pharmacodynamic studies were performed for the optimized rutin SNEDDS formulation. Methodologies: Selection of oil, surfactant and co-surfactant was done on the basis of solubility/miscibility studies. Sefsol+ Vitamin E, Solutol HS 15 and Transcutol P were selected as oil phase, surfactant and co-surfactant respectively. Optimization of SNEDDS formulations was done by a three-factor, three-level (33)BBD. The independent factors were Sefsol+ Vitamin E, Solutol HS15, and Transcutol P. The dependent variables were globule size, self emulsification time (SEF), % transmittance and cumulative percentage drug released. Various response surface graphs and contour plots were constructed to understand the effect of different factor, their levels and combinations on the responses. The optimized Rutin SNEDDS formulation was characterized for various parameters such as globule size, zeta potential, viscosity, refractive index , % Transmittance and in vitro drug release. Ex vivo permeation studies and pharmacokinetic studies were performed for optimized formulation. Antioxidant activity was determined by DPPH and reducing power assays. Anti-inflammatory activity was determined by using carrageenan induced rat paw oedema method. Permeation of rutin across small intestine was assessed using confocal laser scanning microscopy (CLSM). Major findings:The optimized SNEDDS formulation consisting of Sefsol+ Vitamin E - Solutol HS15 -Transcutol HP at proportions of 25:35:17.5 (w/w) was prepared and a comparison of the predicted values and experimental values were found to be in close agreement. The globule size and PDI of optimized SNEDDS formulation was found to be 16.08 ± 0.02 nm and 0.124±0.01 respectively. Significant (p˂0.05) increase in percentage drug release was achieved in the case of optimized SNEDDS formulation (98.8 %) as compared to rutin suspension. Furthermore, pharmacokinetic study showed a 2.3-fold increase in relative oral bioavailability compared with that of the suspension. Antioxidant assay results indicated better efficacy of the developed formulation than the pure drug and it was found to be comparable with ascorbic acid. The results of anti-inflammatory studies showed 72.93 % inhibition for the SNEDDS formulation which was significantly higher than the drug suspension 46.56%. The results of CLSM indicated that the absorption of SNEDDS formulation was considerably higher than that from rutin suspension. Conclusion: Rutin SNEDDS have been successfully prepared and they can serve as an effective tool in enhancing oral bioavailability and efficacy of Rutin.

Keywords: rutin, oral bioavilability, pharamacokinetics, pharmacodynamics

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Authors: Salman Abdulrasaq

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Small and Medium Enterprises (SMEs) has been considered as indices for economic development in a country economy. The development of entrepreneurship skills is therefore necessary. This study, seeks to examine the impact of Entrepreneurship on the Growth of Small Businesses Kwara State, Nigeria. The data used were primarily obtained from the questionnaire administered to the randomly selected areas in the state. Regression statistical tool was employed with aid of SPSS to test the validity of the hypothesis formulated in the study. The study therefore concludes that; the qualities of entrepreneur have impact the growth of Small Businesses s in the selected areas of the state. In view of this, the study recommends that; entrepreneurship development would serve as a tool for the growth of small business enterprises.

Keywords: entrepreneurship, growth, development, Nigeria

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Authors: Abdelkarim Boua, Abdelhakim Chillali

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The study of non-associative structures in algebraic structures has become a separate entity; for, in the case of groups, their corresponding non-associative structure i.e. loops is dealt with separately. Similarly there is vast amount of research on the nonassociative structures of semigroups i.e. groupoids and that of rings i.e. nonassociative rings. However it is unfortunate that we do not have a parallel notions or study of non-associative near-rings. In this work we shall attempt to generalize a few known results and study the commutativity of Jordan ideal in 3-prime near-rings satisfying certain identities involving the Jordan ideal. We study the derivations satisfying certain differential identities on Jordan ideals of 3-prime near-rings. Moreover, we provide examples to show that hypothesis of our results are necessary. We give some new results and examples concerning the existence of Jordan ideal and derivations in near-rings. These near-rings can be used to build a new codes.

Keywords: 3-prime near-rings, near-rings, Jordan ideal, derivations

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Authors: Ahmed Khalaf Reyad Raslan

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Cancer stem cells (CSCs) describe a class of pluripotent cancer cells that behave analogously to normal stem cells in their ability to differentiate into the spectrum of cell types observed in tumors. The de-differentiation processes, such as an epithelial-mesenchymal transition (EMT), are known to enhance cellular plasticity. Here, we demonstrate a new hypothesis to use hybrid superparamagnetic magnetite nanoparticles (Fe₃O₄)- graphene oxide functionalized surface with Collagen to target the cancer stem cell as an early detection tool for cancer. We think that with the use of magnetic resonance imaging (MRI) and the new hybrid system would be possible to track the cancer stem cells.

Keywords: hydrogel, alginate, reduced graphene oxide, collagen

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Authors: Dawood Aghamohammadi, Mahmoud Eidi, Alireza Pishgahi, Azam Esmaeilnejad

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Adenosine has an analgesic and anti-inflammatory role and its injections are used for peri-operative pain management. We want to study efficacy of intrathecal injection of adenosine for post operative radicular pain after lumbar discectomy. 40 patients with unilevel lumbar discectomy who had radicular lower limb pain were treated by 1000 micrograms of intrathecal injection of adenosine. Pain severity, pain killer consumption per day and sleep quality were assessed during a 3 months follow up period. Radicular pain severity was significantly reduced in 3 month follow-up period in comparison to the baseline (F=19760, DF=2.53, p-value<0.001). Further painkiller medication consumption rate in average during 3 month follow-up period after injection was significantly lower in comparison to baseline (F= 19.244, df= 1.98, p-value<0.001). This study suggests that intrathecal injection of adenosine is a safe method in order to reduce postoperative pain after lumbar discectomy.

Keywords: adenosine, intrathecal injection, discectomy, neuropathic pain

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Authors: Soheily Shahram, Banaeifar Abdolali, Yadegari Elham

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Vascular adhesion molecules-1 (VCAM-1) is one of the factors associating obesity and inflammatory lesions like atherosclerosis. The purpose of the present study was to investigate the effects of endurance training on serum concentration of VCAM-1 in overweight women. Thirty female overweight (BMI ≥ 25) voluntarily participated in our study. Subjects were randomly assigned to one of two groups: Endurance training or control group. Training group exercised for 12 weeks, three sessions a week with definite intensity and distance. Pre and post 12 weeks of endurance training blood samples were taken (5cc) in fasting state from all subjects. Data was analyzed via independent t test (p≤0.05). The results showed that endurance training had significant effect on VCAM, body weight, fat percentage, BMI and maximum oxygen consumption (p ≤ 0.05). This study demonstrates that endurance training caused a decrease in the adhesion molecules level and decreasing inflammation, endurance training may perhaps play an effective role in atherosclerosis.

Keywords: endurance training, vascular cell adhesion molecules, overweight women, serum concentration

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Authors: Shun-Qi Zhang, Shu-Yang Zhang, Min Chen

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Applying strong electric field on piezoelectric actuators, on one hand very significant electroelastic material nonlinear effects will occur, on the other hand piezo plates and shells may undergo large displacements and rotations. In order to give a precise prediction of piezolaminated smart structures under large electric field, this paper develops a finite element (FE) model accounting for both electroelastic material nonlinearity and geometric nonlinearity with large rotations based on the first order shear deformation (FSOD) hypothesis. The proposed FE model is applied to analyze a piezolaminated semicircular shell structure.

Keywords: smart structures, piezolamintes, material nonlinearity, strong electric field

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Authors: Amar Ghelani

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People with auditory verbal hallucinations (AVH) who seek support from mental health services commonly report feeling unheard and invalidated in their interactions with social workers and psychiatric professionals. Current mental health training and clinical approaches have proven to be inadequate in addressing the complex nature of voice hearing. Childhood trauma is a key factor in the development of AVH and can render people more vulnerable to hearing both supportive and/or disturbing voices. Lived experiences of racism, poverty, and immigration are also associated with development of what is broadly classified as psychosis. Despite evidence affirming the influence of environmental factors on voice hearing, the Western biomedical system typically conceptualizes this experience as a symptom of genetically-based mental illnesses which requires diagnosis and treatment. Overemphasis on psychiatric medications, referrals, and directive approaches to people’s problems has shifted clinical interventions away from assessing and addressing problems directly related to AVH. The Maastricht approach offers voice hearers and mental health workers an alternative and respectful starting point for understanding and coping with voices. The approach was developed by voice hearers in partnership with mental health professionals and entails an innovative method to assess and create meaning from voice hearing and related life stressors. The objectives of the approach are to help people who hear voices: (1) understand the problems and/or people the voices may represent in their history, and (2) cope with distress and find solutions to related problems. The Maastricht approach has also been found to help voice hearers integrate emotional conflicts, reduce avoidance or fear associated with AVH, improve therapeutic relationships, and increase a sense of control over internal experiences. The proposed oral presentation will be guided by a recovery-oriented theoretical framework which suggests healing from psychological wounds occurs through social connections and community support systems. The presentation will start with a brainstorming exercise to identify participants pre-existing knowledge of the subject matter. This will lead into a literature review on the relations between trauma, intersectionality, and AVH. An overview of the Maastricht approach and review of research related to its therapeutic risks and benefits will follow. Participants will learn trauma-informed coping skills and questions which can help voice hearers make meaning from their experiences. The presentation will conclude with a review of resources and learning opportunities where participants can expand their knowledge of the Hearing Voices Movement and Maastricht approach.

Keywords: Maastricht interview, recovery, therapeutic assessment, voice hearing

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