Modulation of NMDA and AMPA/kainate receptors by tocotrienol-rich fraction and α-tocopherol in glutamate- induced injury of primary astrocytes

Neurodegenerative diseases such as Huntington's, Alzheimer's, Parkinson's disease and stroke are the most common diseases suffered by the aged population. Glutamate is considered as a main excitatory amino acid neurotransmitter in the mammalian central nervous system which can be excitotoxic, playing a key role in series of chronic neurodegenerative diseases. The Vitamin E which consist of tocopherol and tocotrienols, are different in their side chain either in saturated or unsaturated phytyl tail. Previous studies have demonstrated that tocopherol and tocotrienol have protective effects against glutamate toxicity in an astrocytic cell line. The aim of current study is to demonstrate the potential of tocopherol and tocotrienol in protecting glutamate injured primary astrocytes. For this purpose, the primary astrocytes were isolated from mixed glial cells of C57BL/6 mice by using the Easysep Mouse CD11b positive selection kit and cultured in supplemented DMEM. Mixed glial cultures were treated with 50-75 mM L-leucine methyl ester (LME) for 60-90 minutes to improve purity of cultures. The purity of primary astrocytes was measured by flow-cytometer and is approximately 79.4%. The IC20 and IC50 values of glutamate were determined by MTT assay at 10 mM and 100 mM respectively. Cell were induced injury at IC20 and IC50 of glutamate and the effects of tocopherol and tocotrienol rich fraction (TRF) was determined.in pre and post-treatment study. For the high yield of RNA, the IC20 of glutamate was used in the experiment. Exposure to 100 mM of glutamate in primary astrocytes reduced cell viability by approximately 64.75 % and 61.10 % in pre and post treatment study respectively. The mitochondrial membrane potential (MMP) detected in primary astrocytes were assessed with 100, 200 and 300 ng/ml concentration of TRF and α-Tocopherol. The results depicted that pre-treatment with TRF and α-Tocopherol caused the mitochondrial activity to achieve 88.46%, 82.42%, 80.74% and 93.31%, 87.51%, 83.70%, respectively. In post-treatment study, with increase of TRF (100, 200 and 300 ng/ml) concentration causes the increase to 61.21%, 73.01%, 78.43% of MMP value. Similarly, increase of MMP value from 66.12%, 76.46%, and 81.22% was observed with increasing concentration of α-Tocopherol. Then the expression of ionotropic glutamate receptors genes was elucidated using Real-time PCR. The gene of interest consists of the Gria2 (Glutamate Receptor, Inotoropic AMPA), GRIK1 (Glutamate Receptor, Ionotropic, kainate1) and Grin2A (Glutamate Receptor, Ionotropic, N-Methyl D-Aspartate 2A). The results showed that in both pre and post studies, the ionotropic glutamate receptors genes were down regulated after the treatment and α- tocopherol played an important role in down regulating the genes. The most affected genes were Gria2, GriK1 and Grin2A respectively in both pre and post studies. Decreased intracellular calcium concentration also was observed indicating the present of vitamin E altered the polarization of astrocytes. As a conclusion, this study shown that α- tocopherol is more effective and only required low concentration of α- tocopherol for prophylactic purposes compared to post-treatment in primary astrocytes cells

Investigating the Location Pattern of Information and Communication Technology Firms: Case of Vancouver

Despite the volume of literature examining the role of producer amenities (e.g., highways and airports) in firms’ selection of a location, almost no quantitative studies regard the impact of consumer amenities (e.g., theatres and cafes) in attracting firms, as they are hypothesized to attract residents rather than firms or companies. Since the Information and Communication Technology (ICT) sector is regarded as a significant driver and an increasingly important part of the economy in North American and European countries, this research aims to provide insight into the importance of consumer amenities in the location pattern of companies in this sector. Consumer amenities are stated to be important factors in the lifestyle of creative and talented workers such as employees of high-tech industries (Florida, 2003); therefore, this study hypothesizes that ICT firms tend to locate near consumer amenities as they are assumed to be attractive to the talented and highly educated workers that those firms want to employ. ICT firms, because of their size and use, can also be integrated into existing land use, such as downtown where there are lots of amenities. Industrial uses would be more likely to locate near highways because of their land requirements. This thesis looks at a broad pattern as an exploratory study to see if there is a location pattern between consumer amenities and ICT firms’ location. Using census data from Canadian industries, this thesis focuses on exploring a spatial pattern for distribution of ICT companies, both with regards to amenities and the location of firms in other industries. In doing so, information of 66,078 firms that operate in Vancouver and their associated data were obtained from Statistics Canada and the Canadian Business Database. A walkability index is also developed that represents the amenity variable. The findings of this study suggest that ICT firms are more likely to be found in areas with a high concentration of consumer amenities. However, the result shows that there is statistically weak relationship between location of ICT firms and existence of consumer amenities, but this relationship is generally not detected for firms in other sectors. Moreover, the most significant finding of this thesis is that there is a tendency for ICT firms to locate close to and concentrated in downtown cores. As a result, the findings demonstrate that the agglomeration factor in ICT firms’ location decision is more important than the existence of consumer amenities in the place. This study concludes by suggesting that municipalities and their local economic development specialists wanting to attract regional economic growth to better understand and focus on the determinant elements of location decision by ICT firms

The effect of self-determination skills training on academic vitality and optimism in students with hearing loss: a quasi-experimental study

Background: Hearing impairment, even if mild, can delay linguistic development and negatively affect the language acquisition process. This study designed to investigate the effect of self-determination skills training on academic vitality and optimism in students with hearing loss. Method: This was a quasi-experimental study with pretest-posttest design and control group.  The sample consisted of 30 students with hearing loss in Shahroud who were selected by available sampling method and randomly and equally assigned to the experimental and control groups (15 people in each group). The experimental group participated in a self-determination skills training program that was conducted in 8 sessions of 40 minutes (one session per week), while the control group did not participate in this program. Participants were assessed using the Academic Vitality Questionnaire and Optimism Questionnaire. Data were analyzed using univariate and multivariate analysis of covariance tests and SPSS-23 software Results: Considering the differential results of multivariate analysis of covariance for experimental and control groups in the variables of academic vitality (P = 0.001) and academic optimism (P = 0.001), the difference between the experimental and control groups is significant. According to Eta squared, it can be said that in the variables of academic vitality and academic optimism, 33% and 39% of these changes are due to intervention, respectively. Conclusion: This study emphasizes the role of self-determination interventions in positive academic variables. This method can be used in the educational and rehabilitation program of this group of children

Prevalence of Self-medication with Antibiotics amongst Clients Referred to Outpatient University Dental Clinics in Iranian Population: A Questionnaire-based Study

Introduction: Self-medication with antibiotics may increase the risk of inappropriate use and development of antibiotic-resistant bacteria. The aim of this study was to determine the prevalence of self-medication with antibiotics amongst dental outpatients in Iranian population.  Methods and Materials: One thousand and two hundred of dentistry patients, who were referred to dental school clinics in ten major provinces of Iran, participated in this study. A valid self-administered questionnaire regarding self-medication with antibiotics in case of dental pain was used to collect data. Data were analysed using descriptive statistics and Logistic regression analysis. Results: In our study population, the prevalence of self-medication was 42.6%. Amongst the Iranian cities, the highest prevalence of self-medication with antibiotics belonged to the city of Bandar Abbas (64%) and the lowest was seen in the city of Kerman (27.3%). Men were more likely to take antibiotics. Amoxicillin was the mostly used antibiotic. Severe pain, previous self-medications and high costs of dental visits were the most common reasons for self-medication with antibiotics in the investigated population. In addition, the present study showed that marriage, acceptable financial status and high level of education could decrease self-medication with antibiotics. Conclusions: In the current investigation, an alarming fact was that self-medication for dental problems seemed very common amongst the studied population. One of its most important consequences was bacterial resistance. Therefore, there should be plans to promote and prioritize public health awareness and encourage general public’s motivation to reduce the practice of self-medication.Keywords: Antibiotics; Dental Clinics; Prevalence; Self-medicatio

RICCI SOLITONS ON HOPH HYPERSURFACES IN SASAKIAN SPACE FORM

We are studying Ricci solitons on Hoph hypersurfaces in Sasakian space formfM2n+1(c). The rst, we prove that Hoph hypersurfaces of a Sasakian space formfM2n+1(c < 1) with two distinct principal curvatures is shrinking and for c 1,Hoph hypersurfaces with two distinct principal curvatures of a Sasakian space formfM2n+1(c) does not admit a Ricci soliton. We show that there is not any Hoph hyper-surfaces with two distinct principal curvatures in a Sasakian space form fM2n+1(c)with a -Ricci soliton (and Ricci soliton) such that potential vector eld is the Reebvector eld.Then we prove that Hoph hypersurfaces in Sasakian space form fM2n+1(c) withc = 1 does not admit a - Ricci soliton with potential vector eld U and we showthat Ricci soliton on Hoph hypersurfaces M in Sasakian space form fM2n+1(c

Reflection on the Experiences of Disabled People: The Society as a Cause of Growth or Barrier

Introduction: In recent years, based on evidence from several communities, positive psychology researchers have constructed a new conceptualization called “post-traumatic growth”. Based on the theory of symbolic interaction, members of the society, especially family members, play an important role in meaning making of events, quality of life after the accident and its consequences, and whether they experience growth or not. The aim of the present study was decoding experiences of successful disabled people of causing factors (facilitator) or barriers of growth by qualitative method. Method: A qualitative design, based on the content analysis approach, was used to collect and analyze the experiences of 12 disabled people with national and international achievements. Participants were selected by purposeful and snowball sampling method. Semi-structured interviews were used for data collection. The data were analyzed based on the Granheim content analysis approach. Results: The findings showed two main themes: 1) intelligent and noble family with 3 subcategories of initial acceptance and support, interaction with other groups and successful disabled people, and timely attraction and repulsion 2) family as obstacle with 3 subcategories of pity and clumsy support, entertaining instead of being goal-oriented, and ignoring them. Conclusion: Attitudes and family functions have wanted and unwanted effects. They may act as facilitators or obstacles of growth. Understanding these factors based on experiences of disabled people could cause effective changes in the attitudes and beliefs of people. Keywords: People with spinal cord disability, Growth, Content analysi

The relationship between the adequacy of hemodialysis and laboratory parameters

BACKGROUND: The present study was conducted in order to evaluate the factors affecting the adequacy of dialysis and determine the relationship of dialysis adequacy with laboratory parameters.METHODS: This descriptive study was performed on 60 hemodialysis patients of Razi Medical Center of Qaemshahr, Iran, with the history of more than 3 months of dialysis. The participants were selected using census method. Data collection was conducted through a researcher-made questionnaire. Blood samples were collected to evaluate laboratory parameters. The adequacy of dialysis was calculated through the Kt/V parameter. The obtained data were analyzed using descriptive statistical tests.RESULTS: According to the Kt/V criteria, the mean dialysis adequacy index was 1.6 ± 0.22 and 41.7% of the patients had the optimum dialysis adequacy (Kt/V of greater than 1.2), and 43.3% of patients had a dialysis adequacy which was close to the desirable level. There was a significant reverse relationship between dialysis adequacy and alkaline phosphatase (ALP), blood sugar, and body mass index (BMI). Nevertheless, there was no significant relationship between dialysis adequacy and parathyroid hormone ‎(PTH), cholesterol, triglycerides, alanine aminotransferase (ALT), aspartate aminotransferase (AST), calcium, phosphorus, and the number of dialysis sessions per week, duration of each dialysis session, and the history of dialysis (P &gt; 0.05).CONCLUSION: In order to increase the adequacy of dialysis, the blood sugar level of patients should be controlled and patients should be advised to modify their weight using a suitable diet

Investigation of genes associated with primary open-angle glaucoma (POAG) using expression profile analysis

Glaucoma is recognized as one of the most common causes of global blindness observed in various types such as primary open-angle glaucoma (POAG). This condition is characterized by progressive optic neuropathy, leading to damage of optic nerve fibers. Having no symptoms at the beginning, glaucoma results in decreased vision and eventually blindness over several years. Early treatment can prevent the progression of the disease. We performed a study to evaluate differential gene expression in normal control and POAG cases. A total of 179 DEGs were discovered with 60 up-regulated and 119 down-regulated genes. After the selection of DEGs, we constructed the protein-protein interaction network. The result of GO enrichment showed the DEGs involved in antioxidant activity, haptoglobin binding, and oxygen carrier activity. Then Four modules of the primary protein network were obtained using a STRING database, using the K-means method. Next, gene ontology analysis and Kyoto encyclopedia of genes and genomes pathway enrichment were performed for four modules. These genes include TYRP1, FMOD, OGN, PAX6, COL8A2, HLA-DPA1, and HLA-DMB. The results showed that the Selected module is highly related to glaucoma pathogenesis genes. Using integrated bioinformatical analysis, we have identified DEGs candidate genes and pathways involved in glaucoma, which could improve our understanding of the cause and underlying molecular events, and these candidate genes and pathways could be therapeutic targets for glaucoma

Orphan GPR26 Counteracts Early Phases of Hyperglycemia-Mediated Monocyte Activation and Is Suppressed in Diabetic Patients

Diabetes is the ninth leading cause of death, with an estimated 1.5 million deaths worldwide. Type 2 diabetes (T2D) results from the body's ineffective use of insulin and is largely the result of excess body weight and physical inactivity. T2D increases the risk of cardiovascular diseases, retinopathy, and kidney failure by two-to three-fold. Hyperglycemia, as a hallmark of diabetes, acts as a potent stimulator of inflammatory condition by activating endothelial cells and by dysregulating monocyte activation. G-protein couple receptors (GPCRs) can both exacerbate and promote inflammatory resolution. Genome-wide association studies (GWAS) indicate that GPCRs are differentially regulated in inflammatory and vessel cells from diabetic patients. However, most of these GPCRs are orphan receptors, for which the mechanism of action in diabetes is unknown. Our data indicated that orphan GPCR26 is downregulated in the PBMC isolated from T2D patients. In contrast, GPR26 was initially upregulated in human monocytes and PBMC treated with high glucose (HG) levels and then decreased upon chronic and prolonged HG exposure. GPR26 levels were decreased in T2D patients treated with insulin compared to non-insulin treated patients. Moreover, GPR26 inversely correlated with the BMI and the HbA1c of diabetic compared to non-diabetic patients. Knockdown of GPR26 enhanced monocyte ROS production, MAPK signaling, pro-inflammatory activation, monocyte adhesion to ECs, and enhanced the activity of Caspase 3, a pro-apoptotic molecule. The same mechanisms were activated by HG and exacerbated when GPR26 was knocked down. Hence, our data indicated that GPR26 is initially activated to protect monocytes from HG and is inhibited under chronic hyperglycemic conditions