Search results for: inflammatory hypothesis of psychosis

Authors: M. Rajasekar, K. Suresh

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Diosmin is a flavonoid, most abundantly found in many citrus fruits. As a flavonoid, it possesses a multitude of biological activities including anti-hyperglycemic, anti-lipid peroxidative, anti-inflammatory, antioxidant, and anti-mutagenic properties. At this point, we established the anti-proliferative and apoptosis-inducing activities of diosmin in Hep-2 and KB cells. Diosmin has cytotoxic effects through inhibiting cellular proliferation of Hep-2 and KB cells, which leads to the induction of apoptosis, as apparent by an increase in the fraction of cells in the sub-G1phase of the cell cycle. Results exposed that inhibition of cell proliferation is associated with regulation of the Interleukins/STAT pathway. In addition, Diosmin treatment with Hep-2 and KB cells actively stimulated reactive oxygen species (ROS) and mitochondrial membrane depolarization. And also an imbalance in the Bax/Bcl-2 ratio triggered the caspase cascade and shifting the balance in favor of apoptosis. These observations conclude that Diosmin induce apoptosis via Interleukins /STAT-mediated pathway.

Keywords: diosmin, apoptosis, antioxidant, STAT pathway

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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, Mona G. Khalil, Hemat A. Elariny, Shereen S. El Shaer

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Background: Aluminium (Al) is very abundant metal in the earth’s crust. It is a constituent of cooking utensils, medicines, cosmetics, some foods and food additives. Salts of Al are widely used in the treatment of drinking water for purification purposes. Excessive and prolonged exposure to Al causes oxidative stress and impairment of many physiological functions. Its accumulation in liver and kidney causes hepatotoxicity and nephrotoxicity. Social isolation (SI) or Protein malnutrition (PM) also increases oxidative stress and may enhance the toxicity of Al as well as the degeneration in liver and kidney. Epigallocatechin-3-gallate (EGCG) is the most abundant catechin in green tea and has strong antioxidant as well as anti-inflammatory activities and can protect against oxidative stress-induced degenerations. Objective: To study the influence of stress or PM on Al-induced nephrotoxicity and hepatotoxicity in rats, as well as on the potential role of EGCG in providing protection. Methods: Rats received daily AlCl3 (70 mg/kg, IP) for three weeks (Al-toxicity groups) except one normal control group received saline. Al-toxicity groups were divided into four treated and four untreated groups; treated rats received EGCG (10 mg/kg, IP) together with AlCl3. One group of both treated and untreated rats served as control for each of them, and the others were subjected to either stress (mild using isolation or high using electric shock) or to PM (10% casein diet). Specimens of liver and kidney were used for assessment of levels of inflammatory mediators as TNF-α, IL6β, nuclear factor kappa B (NF-κB), oxidative stress (MDA, SOD, TAC, NO), Caspase-3 and for DNA fragmentation as well as for histopathological examinations. Biochemical changes were also measured in the serum as total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea as well as the level of Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and lactate deshydrogenase (LDH). Results: Nephrotoxicity and hepatotoxicity induced by Al were enhanced in rats exposed to stress and to PM. The influence of stress was more pronounced than PM. Al-toxicity was indicated by the increase in liver and kidney MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3, DNA fragmentation and in ALT, AST, ALP, LDH and total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea levels, together with the decrease in total proteins, SOD, TAC. EGCG provided protection against hazards of Al as indicated by the decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation as well as in levels of ALT, AST, ALP, LDH and total lipids, cholesterol, triglycerides, glucose, proteins, bilirubin, creatinine and urea in liver and kidney, together with the increase in total proteins, SOD, TAC and confirmed by histopathological examinations. It provided more pronounced protection in high stressful conditions than in mild one than in PM. Conclusion: Stress have a bad impact on Al-induced nephrotoxicity and hepatotoxicity more than PM. Thus it can clarify and maximize the role of EGCG in providing protection. Consequently, administration of EGCG is advised with excessive Al-exposure to avoid nephrotoxicity and hepatotoxicity especially in populations more subjected to stress or PM.

Keywords: aluminum, stress, protein malnutrition, nephrotoxicity, hepatotoxicity, epigallocatechin-3-gallate, rats

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Authors: L. Mercier, D. Beladjine, K. Beddiar

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The digital transition of building in France brings many changes which some have been able to face very quickly, while others are struggling to find their place and the interest that BIM can bring in their profession. BIM today is already adopted or initiated by construction professionals. However, this change, which can be drastic for some, prevents them from integrating it definitively. This is the case with architects. The profession is shared on the practice of BIM in its exercise. The risk of not adopting this new working method now and of not wanting to switch to its new digital tools leads us to question the future of the profession in view of the gap that is likely to be created within project management. In order to deal with the subject efficiently, our work was based on a documentary watch on BIM and then on the profession of architect, which allowed us to establish links on these two subjects. The observation of the economic model towards which the agencies tend and the trend of the sought after profiles made it possible to develop the opportunities and the brakes likely to impact the future of the profession of architect. The centralization of research directs work towards the conclusion that the model implemented by companies does not allow to integrate BIM within their structure. A solution hypothesis was then issued, focusing on the development of agencies through the diversity of profiles, skills to be integrated internally with the aim of diversifying their skills, and their business practices. In order to address this hypothesis of a multidisciplinary agency model, we conducted a survey of architectural firms. It is built on the model of Anglo-Saxon countries, which do not have the same functioning in comparison to the French model. The results obtained showed a risk of gradual disappearance on the market from small agencies in favor of those who will have and could take this BIM working method. This is why the architectural profession must, first of all, look at what is happening within its training before absolutely wanting to diversify the profiles to integrate into its structure. This directs the study on the training of architects. The schools of French architects are generally behind schedule if we allow the comparison to the schools of engineers. The latter is currently experiencing a slight improvement with the emergence of masters and BIM options during the university course. If the training of architects develops towards learning BIM and the agencies have the desire to integrate different but complementary profiles, then they will develop their skills internally and therefore open their profession to new functions. The place of BIM Management on projects will allow the architect to remain in control of the project because of their overall vision of the project. In addition, the integration of BIM and more generally of the life cycle analysis of the structure will make it possible to guarantee eco-design or eco-construction by approaching the constraints of sustainable development omnipresent on the planet.

Keywords: building information modelling, BIM, BIM management, BIM manager, BIM architect

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Authors: Triana Fitriastuti, Pipiet Larasatie, Alex Vanderstraten

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Many scholars have demonstrated the negative impacts of the perception of organizational politics on organizational outcomes. The model proposed in this study analyzes the impact of the perception of organizational politics on job satisfaction. In the same way, ingratiation as a moderator variable is tested. We applied regression analysis to test the hypothesis. The findings of the current research, which was conducted with 240 employees in the public sector in Indonesia, show that the perception of organizational politics has a negative effect on job satisfaction. In contrast, ingratiation plays a role that fully moderates the relationship between organizational politics and organizational outcomes and changes the correlation between the perception of organizational politics on job satisfaction. Employees who use ingratiation as a coping mechanism tend to do so when they perceive a high degree of organizational politics.

Keywords: ingratiation, impression management, job satisfaction, perception of organizational politics

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Authors: Athar Imtiaz, Abduljalil S. Al-Mudhary, Taha Mirhashemi, Roslina Ibrahim

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Information Technology (IT) is being used by almost all organizations throughout the world. However, its success at supporting and improving business is debatable. There is always the risk of IT project failure and studies have proven that a large number of IT projects indeed do fail. There are many components that further the success of IT projects; these have been studied in previous studies. Studies have found the most necessary components for success in software development projects, executive information systems etc. In this study, previous literature that has looked into these success promoting factors have been critically reviewed and analyzed. Fifteen critical Success Factors (CSF) of IT projects were enlisted and examined. These factors can be applied to all IT projects and is not specific to a particular type of IT/IS project. A hypothesis was also generated after the evaluation of the factors.

Keywords: critical success factors, CSF, IT projects, IS projects, software development projects

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Authors: Mark Berry

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A number of studies have identified several factors involved in the malignant progression of cancer cells. The Primary modulator in driving inflammation to these transformed cells has been identified as the transcription factor known as nuclear factor-κB. This essential regulator of inflammation and the development of cancer, combined with a microenvironment of inflammation and signaling molecules, plays a major role in the malignant progression of cancer, and this progression is the result of the mutagenic predisposition of persistent substances that combat infection at tumor sites and other areas of chronic inflammation. Inflammation-induced tumors, and their inflammatory cells and regulators may be the primary source of metastasis of tumor cells through angiogenesis. Previous research on cytokines and chemokines, including their downstream targets, has been the focus of the cancer/inflammation connection. The identification of the biological mechanisms of other proteins vital to the inflammation cascade and their interactions are crucial to novel and effective therapeutic protocols for the treatment of inflammation-induced cancers. The Ancelim HSRP Protocol is just such a therapeutic intervention.

Keywords: ancelim, cancer, inflammation, tumor

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Authors: Megan L. Srinivas

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Individuals with underlying rheumatologic diseases such as dermatomyositis may not adequately respond to tuberculin (PPD) skin tests, creating false negative results. These illnesses are frequently treated with immunosuppressive therapy making proper identification of TB infection imperative. A 59-year-old Filipino man was diagnosed with dermatomyositis on the basis of rash, electromyography, and muscle biopsy. He was initially treated with IVIG infusions and transitioned to oral prednisone and mycophenolate. The patient’s symptoms improved on this regimen. Six months after starting mycophenolate, the patient began having fevers, night sweats, and productive cough without hemoptysis. He moved from the Philippines 5 years prior to dermatomyositis diagnosis, denied sick contacts, and was PPD negative both at immigration and immediately prior to starting mycophenolate treatment. A third PPD was negative following the onset of these new symptoms. He was treated for community-acquired pneumonia, but symptoms worsened over 10 days and he developed watery diarrhea and a growing non-tender, non-mobile mass on the left side of his neck. A chest x-ray demonstrated a cavitary lesion in right upper lobe suspicious for TB that had not been present one month earlier. Chest CT corroborated this finding also exhibiting necrotic hilar and paratracheal lymphadenopathy. Neck CT demonstrated the left-sided mass as cervical chain lymphadenopathy. Expectorated sputum and stool samples contained acid-fast bacilli (AFB), cultures showing TB bacteria. Fine-needle biopsy of the neck mass (scrofula) also exhibited AFB. An MRI brain showed nodular enhancement suspected to be a tuberculoma. Mycophenolate was discontinued and dermatomyositis treatment was switched to oral prednisone with a 3-day course of IVIG. The patient’s infection showed sensitivity to standard RIPE (rifampin, isoniazid, pyrazinamide, and ethambutol) treatment. Within a week of starting RIPE, the patient’s diarrhea subsided, scrofula diminished, and symptoms significantly improved. By the end of treatment week 3, the patient’s sputum no longer contained AFB; he was removed from isolation, and was discharged to continue RIPE at home. He was discharged on oral prednisone, which effectively addressed his dermatomyositis. This case illustrates the unreliability of PPD tests in patients with long-term inflammatory diseases such as dermatomyositis. Other immunosuppressive therapies (adalimumab, etanercept, and infliximab) have been affiliated with conversion of latent TB to disseminated TB. Mycophenolate is another immunosuppressive agent with similar mechanistic properties. Thus, it is imperative that patients with long-term inflammatory diseases and high-risk TB factors initiating immunosuppressive therapy receive a TB blood test (such as a quantiferon gold assay) prior to the initiation of therapy to ensure that latent TB is unmasked before it can evolve into a disseminated form of the disease.

Keywords: dermatomyositis, immunosuppressant medications, mycophenolate, disseminated tuberculosis

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Authors: Maxwel F. Silva, José Geraldo Pedrosa

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This paper is a study about the voyage of Adolfo Caminha to the USA in the late nineteenth century described in “No país dos ianques”. The hypothesis is that the USA constitutes a civilizing reference that moves away from Europe. The Americanism expression it means that the Yankees have invented a new repertoire through which built a new idea of civilization. The base is European, but your architecture is new. This paper is not concerned with the meanings and uses of the Americanism expression among the Yankees, but with the ways in which the America were understood by otherness, especially in the late nineteenth and early twentieth century. In this way, this study discusses the concept of Americanism in the thought of Adolfo Caminha and it is relation with the Brazil in the late nineteenth century, especially in questions about democracy, liberty and progress.

Keywords: Adolfo Caminha, Americanism, discourse, voyage

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Authors: Farah El Mohtadi, Richard d'Arcy, Nicola Tirelli

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Since 40 years, poly (ethylene glycol) (PEG) has been the gold standard in biomaterials and drug delivery, because of its combination of chemical and biological inertness. However, the possibility of its breakdown under oxidative conditions and the demonstrated development of anti-PEG antibodies highlight the necessity to develop carriers based on materials with increased stability in a challenging biological environment. Here, we describe the synthesis of polysulfide via anionic ring-opening polymerization. In vitro, the synthesized polymer was characterized by low toxicity and a level of complement activation (in human plasma) and macrophage uptake slightly lower than PEG and poly (2‐methyl-2‐oxazoline) (PMOX), of a similar size. Importantly, and differently from PEG, on activated macrophages, the synthesized polymer showed a strong and dose-dependent ROS scavenging activity, which resulted in the corresponding reduction of cytokine production. Therefore, the results from these studies show that polysulfide is highly biocompatible and are potential candidates to be used as an alternative to PEG for various applications in nanomedicine.

Keywords: PEG, low toxicity, ROS scavenging, biocompatible

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Authors: C. Slim

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Traditional techniques for analyzing time series are based on the notion of stationarity of phenomena under study, but in reality most economic and financial series do not verify this hypothesis, which implies the implementation of specific tools for the detection of such behavior. In this paper, we study nonstationary non-seasonal time series tests in a non-exhaustive manner. We formalize the problem of nonstationary processes with numerical simulations and take stock of their statistical characteristics. The theoretical aspects of some of the most common unit root tests will be discussed. We detail the specification of the tests, showing the advantages and disadvantages of each. The empirical study focuses on the application of these tests to the exchange rate (USD/TND) and the Consumer Price Index (CPI) in Tunisia, in order to compare the Power of these tests with the characteristics of the series.

Keywords: stationarity, unit root tests, economic time series, ADF tests

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Authors: Maryam Hamedanlou, Shahla Hajializadeh

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The transdermal drug delivery system is one of the types of novel drug delivery system that the drug is absorbed into the skin. The major considerations for designing and producing transdermal patch are small size, suitable drug release and good adhering. In this study, drug-in-adhesive transdermal patch contained non-steroidal anti-inflammatory ketoprofen is prepared. Also, the effect of non-woven fabric and plastic backing layers on adhesion properties is assessed. The results of the test, demonstrated the use of plastic backing layer increases tack and peel rather than non-woven fabric type. The balance tack with plastic backing layer patch is 6.7 (N/mm2), and the fabric one is 3.8 (N/mm2), and their peel is 9.2 (N/25mm) and 8.3 (N/25mm) by arrangement.

Keywords: transdermal drug delivery system, single layer patch of ketoprofen, plastic layer, fabric backing layer

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Authors: Mohamed El Moctar Abeidi

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The indazole derivatives exhibit a wide spectrum of biological activities. They are known for their anti-tumor, antiplatelet, anti-viral, anti-microbial, anti-inflammatory, anti-leishmania and even anti-spermatogen. As part of our research on the synthesis of a number of heterocycles capable of exhibiting a biological and pharmacological property, due to our ongoing interest in the development of a simple and low-cost procedure for obtaining heterocyclic compounds that may have an interest for medicinal purposes. We present in this work the synthesis of 6-nitro-indazoles derivatives, using two different methods. the first method is the alkylation of Nitroindazole by two different alkylating agents under the conditions of solid/liquid phase transfer catalysis in N, N-dimethylformamide (DMF) in the presence of potassium carbonate (K₂CO₃) as a base, and tetra-n-butylammonium bromide (BTBA) as a catalyst. While the other method is the 1,3-dipolar cycloaddition, in this case, we have undertaken the preparation of bi-heterocyclic containing the 6-nitroindazole associate with group of isoxazoline, isoxazole or 1,2,3-Triazole under normal conditions and, under the catalytic conditions of the click chemistry we were also able to determine the structures without any ambiguity by the ¹H and ¹³C NMR.

Keywords: indazole, 6-nitroindazole, isoxazole, 1, 2, 3-Triazole

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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: Bita Mashayekhi, Hamid Kalhornia

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One of the most important roles of financial reporting is improving the firms’ investment decisions; however, there is not much supporting evidence for this claim in emerging markets like Iran. In this study, the effect of financial reporting transparency in investment efficiency of Iranian firms has been investigated. In order to do this, 336 listed companies on Tehran Stock Exchange (TSE) has been selected for time period 2012 to 2015 as research sample. For testing our main hypothesis, we classified sample firms into two groups based on their deviation from expected investment: under-investment and over-investment cases. The results indicate that there is positive significant relationship between financial transparency and investment efficiency. In the other words, transparency can mitigate both underinvestment and overinvestment situations.

Keywords: corporate governance, disclosure, investment decisions, investment efficiency, transparency

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Authors: Eva Kotlánová

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After recession that began in 2007 in the United States and subsequently spilled over the Europe we could expect recovery of economic growth. According to the last estimation of economic progress of European countries, this recovery is not strong enough. Among others, it will depend on economic policy, where and in which way, the economic indicators will proceed. Economic theories postulate that the economic subjects prefer stably, continual economic policy without repeated and strong fluctuations. This policy is perceived as support of economic growth. Mostly in crises period, when the government must cope with consequences of recession, the economic policy becomes unpredictable for many subjects and economic policy uncertainty grows, which have negative influence on economic growth. The aim of this paper is to use panel regression to prove or disprove this hypothesis on the example of five largest European economies in the period 2008–2012.

Keywords: economic crises in Europe, economic policy, uncertainty, panel analysis regression

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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: 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: 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: 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: 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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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: 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: 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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