Search results for: antiresorptive drug related osteonecrosis

Authors: Donna L. Roberts

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Heroin has appeared on the drug scene before. Yet the current opioid crisis differs in significant ways. In order to address the grave challenges, this epidemic poses, the unique precipitating and sustaining conditions must be thoroughly examined. This research explored the various aspects of the political, economic, and social conditions that created a 'perfect storm' for the evolution and maintenance of the current opioid crisis. Specifically, the epidemiology, demographics, and progression of addiction inherent in the current crisis were compared to the patterns of past opioid use. Additionally, the role of pharmaceutical companies and prescribing physicians, the nature and pharmaceutical properties of the available substances and the changing socioeconomic climate were considered. Results indicated that the current crisis differs significantly with respect to its evolution, magnitude, prevalence, and widespread societal effects. Precipitated by a proliferation of prescription medication and sustained by the availability of cheaper, more potent street drugs, including new versions of synthetic opioids, the current crisis presents unprecedented challenges affecting a wider and more diverse segment of society. The unique aspects of this epidemic demand unique approaches to addressing the problem. Understanding these differences is a key step in working toward a practical and enduring solution.

Keywords: addiction, drug abuse, opioids, opioid crisis

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Authors: Kye Gilder, Kevin Shan, Amy Halseth, Steve Smith

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This study assessed the effect of prolonged-release naltrexone 32 mg/bupropion 360 mg (NB) on cardiovascular (CV) events in overweight/obese participants at elevated CV risk. Participants must lose ≥2% body weight at 16 wks, without a sustained increase in blood pressure, to continue drug. Only serious adverse events (SAE) and adverse events leading to discontinuation of study drug (AELDSD) were collected. The study was terminated early after second interim analysis with 50% of all CV events. Data on CV endpoints has been published. Current analyses focused on AEs in participants on antidepressants at baseline, as these individuals were excluded from Phase 3 trials. Intent-to-treat (ITT) population (placebo [PBO] N=4450, NB N=4455) was 54.5% female, 83.5% white, mean age of 61 yrs, mean BMI 37.3 kg/m2, 22.8% with a history of depression, 23.1% on antidepressants, including 15.4% on an SSRI. SAEs in participants receiving antidepressants was similar between NB (10.7%) and PBO (9.9%) and also similar to overall population (9.5% NB, 8.1% PBO). SAEs in those on SSRIs were similar, 10.1% NB and PBO 9.4%. For those on SSRIs or other antidepressants, AELDSDs were similar to overall population and were primarily GI disorders. Obesity increases the risk of developing depression. For participants taking NB and antidepressants, including SSRIs, there is a similar AE profile as the overall population and data revealed no evidence of an additional health risk with combined use.

Keywords: antidepressant, Contrave, Mysimba, obesity, pharmacotherapy

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Authors: Indu Lata Kanwar, Preeti K. Suresh

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The aim of this study is to fabricate hydroxyapatite based nanocomposites for local drug delivery in periodontal pockets. Hydroxyapatite is chemically similar to the mineral component of bones and hard tissues in mammals. Synthetic biocompatibility and bioactivity with human teeth and bone, making it very attractive for biomedical applications. Nanocomposite is a multiphase solid material where one of the phases has one, two or three dimensions of less than 100 nanometres (nm), or structures having nano­scale repeat distances between the different phases that make up the material. Nanostructured calcium phosphate materials play an important role in the formation of hard tissues in nature. It is reported that calcium phosphates materials in nano-size can mimic the dimensions of constituent components of calcified tissues. Nano-sized materials offer improved performances compared with conventional materials due to their large surface-to-volume ratios. The specific biological properties of the nanocomposites, as well as their interaction with cells, include the use of bioactive molecules. The approach of periodontal tissue engineering is considered promising to restore bone defect through the use of engineered materials with the aim that they will prohibit the invasion of fibrous connective tissue and help repair the function during bone regeneration.

Keywords: bioactive, hydroxyapatite, nanocomposities, periondontal

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Authors: D. Supaporn, B. Julaluk

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The purposes of this study were to study symptom cluster, functional status and quality of life of patients with chronic obstructive pulmonary disease (COPD), and to examine factors related to and predicting symptom cluster, functional status and quality of life of COPD patients. The sample was 180 COPD patients multi-stage random sampling from 4 hospitals in the eastern region, Thailand. The research instruments were 8 questionnaires and recorded forms measuring personal and illness data, co-morbidity, physical and psychological symptom, health status perception, social support, and regimen adherence, functional status and quality of life. Spearman rank and Pearson correlation coefficient, exploratory factors analysis and standard multiple regression were used to analyzed data. The findings revealed that two symptom clusters were generated: physical symptom cluster including dyspnea, fatigue and insomnia; and, psychological symptom cluster including anxiety and depression. Scores of physical symptom cluster was at moderate level while that of psychological symptom cluster was at low level. Scores on functional status, social support and overall regimen adherence were at good level whereas scores on quality of life and health status perception were at moderate level. Disease severity was positively related to physical symptom cluster, psychological symptom cluster and quality of life, and was negatively related to functional status at a moderate level (rs = .512, .509, .588 and -.611, respectively). Co-morbidity was positively related to physical symptom cluster and psychological symptom cluster at a low level (r = .179 and .176, respectively). Regimen adherence was negatively related to quality of life and psychological symptom cluster at a low level (r=-.277 and -.309, respectively), and was positively related to functional status at a moderate level (r=.331). Health status perception was negatively related to physical symptom cluster, psychological symptom cluster and quality of life at a moderate to high level (r = -.567, -.640 and -.721, respectively) and was positively related to functional status at a high level (r = .732). Social support was positively related to functional status (r=.235) and was negatively related to quality of life at a low level (r=-.178). Physical symptom cluster was negatively related to functional status (r= -.490) and was positively related to quality of life at a moderate level (r=.566). Psychological symptom cluster was negatively related to functional status and was positively related to quality of life at a moderate level (r= -.566 and .559, respectively). Disease severity, co-morbidity and health status perception could predict 40.2% of the variance of physical symptom cluster. Disease severity, co-morbidity, regimen adherence and health status perception could predict 49.8% of the variance of psychological symptom cluster. Co-morbidity, regimen adherence and health status perception could predict 65.0% of the variance of functional status. Disease severity, health status perception and physical symptom cluster could predict 60.0% of the variance of quality of life in COPD patients. The results of this study can be used for enhancing quality of life of COPD patients.

Keywords: chronic obstructive pulmonary disease, functional status, quality of life, symptom cluster

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Authors: Oktavia Eka Puspita

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The possibility of using Solid Lipid Nanoparticles (SLN) for topical use is an interesting feature concerning this system has occlusive properties on the skin surface therefore enhance the penetration of drugs through the stratum corneum by increased hydration. This advantage can be used to enhance the drug penetration of topical delivery such as Diclofenac sodium for the relief of signs and symptoms of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. The purpose of this study was focused on the preparation and physical characterization of Diclofenac sodium loaded SLN (D-SLN). D loaded SLN were prepared by hot homogenization followed by ultrasonication technique. Since the occlusion factor of SLN is related to its particle size the formulation of D-SLN in present study two formulations different in its surfactant contents were prepared to investigate the difference of the particle size resulted. Surfactants selected for preparation of formulation A (FA) were lecithin soya and Tween 80 whereas formulation B (FB) were lecithin soya, Tween 80, and Sodium Lauryl Sulphate. D-SLN were characterized for particle size and distribution, polydispersity index (PI), zeta potential using Beckman-Coulter Delsa™ Nano. Overall, the particle size obtained from FA was larger than FB. FA has 90% of the particles were above 1000 nm, while FB has 90% were below 100 nm.

Keywords: solid lipid nanoparticles, hot homogenization technique, particle size analysis, topical administration

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Authors: Daniel Aberdam

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Haploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by reduced visual acuity. Patients have also progressive disorders including cataract, glaucoma and corneal abnormalities making their condition very challenging to manage. Aniridia-related keratopathy (ARK), caused by a combination of factors including limbal stem-cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface, affects up to 95% of patients. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub-epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. Although animal models partially recapitulate this disease, there is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation. We used genome editing (CRISPR/Cas9 technology) to introduce a nonsense mutation found in patients into one allele of the PAX6 gene into limbal stem cells. Resulting mutated clones, expressing half of the amount of PAX6 protein and thus representative of haploinsufficiency were further characterized. Sequencing analysis showed that no off-target mutations were induced. The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also reduced. Remarkably, addition of soluble recombinant PAX6 protein into the culture medium was sufficient to activate endogenous PAX6 gene and, as a consequence, rescue the phenotype. It strongly suggests that our in vitro model recapitulates well the epithelial defect and becomes a powerful tool to identify drugs that could rescue the corneal defect in patients. Furthermore, we demonstrate that the homeotic transcription factor Pax6 is able to be uptake naturally by recipient cells to function into the nucleus.

Keywords: Pax6, crispr/cas9, limbal stem cells, aniridia, gene therapy

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Authors: Melek Göregenli, Pelin Karakuş

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This present study explored the acculturation strategies and urban related identity of Turk and Kurd internal migrants from different regions of Turkey who resettled in three big cities in the west. Besides we aimed at a comparative analysis of acculturation strategies and urban-related identity of voluntary and internally displaced Kurd migrants. Particularly we explored the role of migration type, satisfaction with migration decision, urban-related identity and several socio demographic variables as predictors of Kurds’ integration strategy preference. The sample consisted of 412 adult participants from Izmir (64 females, 86 males); Ankara (76 females, 75 males); and Istanbul (43 females, 64 males and four unreported). In terms of acculturation strategies, assimilation was found to be the most preferred acculturation attitude among Turks whereas separation was found to be most endorsed acculturation attitude among Kurds. The migrants in Izmir were found to prefer assimilation whereas the migrants in Ankara prefer separation. Concerning urban-related identity mean scores, Turks reported higher urban-related identity scores than Kurds. Furthermore the internal migrants in Izmir were found to score higher in urban-related identity than the migrants living in Istanbul and Ankara. The results of the regression analysis revealed that gender, length of residence and migration type were the significant predictors of integration preference of Kurds. Thus, whereas gender and migration type had significant negative associations; length of residence had positive significant associations with Kurds integration preference. Compared to female Kurds, male Kurds were found to be more integrated. Furthermore, voluntary Kurd migrants were more favour of integration than internally displaced Kurds. The findings supported the significant associations between acculturation strategies and urban-related identity with either group.

Keywords: acculturation, forced migration, internal displacement, internal migration, Turkey, urban-related identity

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Authors: S. J. Sirima, C. Thirawan, R.Puntharikorn, K. Ungsumalin, J. Kaemwich

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Acinetobacter spp. is a gram negative bacterium causing the high incidence of multi-drug resistance in patients admitted to an intensive care unit. A hundred isolates of Imipenem-resistant Acinetobacter spp. isolated from patients admitted at tertiary health care center, Northeastern region, Ubon Ratchathani, Thailand, were subjected to modified Hodge test and combined disc test in order to evaluate the production of carbapenemases. The results revealed that about 35% of isolates were found to be carbapenemases producers. In addition, multiplex polymerase chain reactions were performed to detect blaOXA-like genes. It showed that 92% of isolates possess blaOXA-51-like and blaOXA-23-like genes. However, blaOXA-58-like gene was detected in only 8 isolates. No detection of blaOXA-24-like gene was observed in all isolates. In conclusion, an ability to produce carbepenemases would be an important mechanism of multi-drug resistance among clinical isolates of Acinetobacter spp. at tertiary health care center, Northeastern region, Ubon Ratchathani, Thailand. Furthermore, it was likely that the class D carbapenemases genes, blaOXA-51-like and blaOXA-23-like, might contribute to imipenem-resistance exhibiting among isolates.

Keywords: Acinetobacter spp., blaOXA-like genes, carbapenemases, tertiary health care center

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Authors: Hae Jeong Park, Joo-Ho Chung

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In this study, the effect of essential oil from Chamaecyparis obtuse (EOCO) on early life stress using maternal separation (MS) rats was investigated. Anxiety-related behaviors were examined in MS rats using the elevated plus-maze (EPM) test. The changes of gene expressions by EOCO in the hippocampus of MS rats were analyzed using a microarray method. Rats in the MS groups were separated from their respective mothers from postnatal day (pnd) 14 to 28. Rats in the EOCO-treated groups were exposed to EOCO for 1 h or 2 h by inhalation from pnd 21 to 28. The EOCO-treated MS rats showed decreased anxiety-related behaviors compared to the MS rats in the EPM test. In the microarray analysis, EOCO downregulated the expressions of cytokine genes such as Ccl2, Il6, Cxcl10, Ccl19, and Il1rl in the hippocampus of MS rats, and it was also confirmed through RT-PCR. In particular, the expressions of Ccl2 and Il6 were predominantly decreased by EOCO in the hippocampus of MS rats. Interestingly, their protein expressions were also reduced by EOCO in MS rats. These results indicate that EOCO decreases MS-induced anxiety-related behaviors, and modulate cytokines, particularly Ccl2 and Il6, in the hippocampus of MS rats.

Keywords: anxiety-related behavior, Chamaecyparis obtuse, cytokine gene, early-life stress, maternal separation

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Authors: T. Mahesh, M. K. Samanta

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Antibody dug conjugate (ADC’s) concept is a less explored and more trustable for the treatment of Type 1 diabetes (T1D). T1D is thought to arise from selective immunologically mediated destruction of the insulin- producing β-cells in the pancreatic islets of Langerhans with consequent insulin deficiency. It is evident that type 1 diabetes can be conquered, by 1) to stop immune destruction of βcells, 2) to replace or regenerate β-cells, and 3) to preserve β-cell function and mass. Many studies found that the regulatory T cells (Tregs) are crucial for the maintenance of immunological tolerance. Immune tolerance is liable for the activation of the Th1 response. The important role of Th1 response in pathology of T1D entails the depletion of CD4+ T cells, which initiated the use of anti-CD4 monoclonal antibodies (mAbs) against CD4+ T cells to interfere with induction of T1D.Insulin is regulated by Glucagon-Like Peptide-1 hormone (GLP-1) which also stimulates β-cells proliferation as the half-life of GLP-1 harmone is less due to rapid degradation by DPP-IV enzyme an alternative DPP-IV-inhibitors can increase the half-life of GLP-1 through which it conquers the replacement and reserve β-cells mass. Thus in the present study Anti-CD4 mAb was conjugated with Sitagliptin which is a DPP-IV inhibitor Drug loaded in Nanoparticles through Sulfo-MBS cross-linkers. The above study can be an effective approach for treatment to overcome the Passive subcutaneous insulin therapy.

Keywords: antibody drug conjugates, anti-CD4 Mab, DPP IV inhibitors, GLP-1

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Authors: Davoud Maleki, Neda Zamani

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The purpose of this research was to investigate the factors affecting the organizational pathology of knowledge production in Islamic Azad University. The present research method is quantitative. It was a survey type and applied research in terms of its purpose. The statistical population of the present study included all full-time professors of the Islamic Azad Universities in the North, South, East, West and Central regions, including the Islamic Azad Universities of Sari, Isfahan, Kerman, Khorramabad and Shiraz, and their total number was 1389, based on the Cochran formula. 305 people were selected as the sample size by random sampling method. The research tool was a researcher-made questionnaire, whose validity was calculated from the professors' point of view and its reliability was calculated based on Cronbach's alpha and was 0.89. For data analysis, confirmatory factor analysis and structural equations were used with Smart3 Pls software. The findings showed that the variables of strategy, structure and process directly and the variable of strategy explained indirectly through the variables of structure and process 96.8% of the pathology of knowledge production. Also, structure 49.6% and process variable 58.4% explain the pathology of knowledge production. 38% of knowledge production changes related to the direct effect of strategy, 39% of knowledge production changes Related to the effect of structure, 32% of the changes in knowledge production are related to the direct effect of the process, 70.5% of the changes related to the structure are related to the direct effect of the strategy, 36.5% of the changes related to the process are related to the direct effect of the strategy, 46.3 Percentage of process variable changes It is related to the direct effect of the structure. According to the obtained results, it can be acknowledged that the pathology model of knowledge production in Islamic Azad University can be used as an effective model in the pathology of knowledge production and can improve the scientific level of knowledge producers.

Keywords: pathology of knowledge production, strategic issues, process issues, Islamic Azad University

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Authors: Shraddha Gopal, Jayam Lazarus

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Aims: To study the referral practice and impact of DAT-scan in the diagnosis or exclusion of Parkinson’s disease. Settings and Designs: A retrospective study Materials and methods: A retrospective study of the results of 60 patients who were referred for a DAT scan over a period of 2 years from the Department of Neurology at Northern Lincolnshire and Goole NHS trust. The reason for DAT scan referral was noted under 5 categories against Parkinson’s disease; drug-induced Parkinson’s, essential tremors, diagnostic dilemma, not responding to Parkinson’s treatment, and others. We assessed the number of patients who were diagnosed with Parkinson’s disease against the number of patients in whom Parkinson’s disease was excluded or an alternative diagnosis was made. Statistical methods: Microsoft Excel was used for data collection and statistical analysis, Results: 30 of the 60 scans were performed to confirm the diagnosis of early Parkinson’s disease, 13 were done to differentiate essential tremors from Parkinsonism, 6 were performed to exclude drug-induced Parkinsonism, 5 were done to look for alternative diagnosis as the patients were not responding to anti-Parkinson medication and 6 indications were outside the recommended guidelines. 55% of cases were confirmed with a diagnosis of Parkinson’s disease. 43.33% had Parkinson’s disease excluded. 33 of the 60 scans showed bilateral abnormalities and confirmed the clinical diagnosis of Parkinson’s disease. Conclusion: DAT scan provides valuable information in confirming Parkinson’s disease in 55% of patients along with excluding the diagnosis in 43.33% of patients aiding an alternative diagnosis.

Keywords: DATSCAN, Parkinson's disease, diagnosis, essential tremors

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Authors: Osman Turkoglu, Alvin Estilo, Ritu Gupta, Liliam Pineda-Salgado, Rajesh Pandey

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Background: Hepatotoxicity can be linked to a variety of clinical symptoms and histopathological signs, posing a great challenge in the surveillance of suspected drug-induced liver injury (DILI) cases in the safety database. Additionally, the majority of such cases are rare, idiosyncratic, highly unpredictable, and tend to demonstrate unique individual susceptibility; these qualities, in turn, lend to a pharmacovigilance monitoring process that is often tedious and time-consuming. Objective: Develop a multifactorial algorithm to assist pharmacovigilance physicians in identifying high-risk hepatotoxicity cases associated with DILI from the sponsor’s safety database (Argus). Methods: Multifactorial selection criteria were established using Structured Query Language (SQL) and the TIBCO Spotfire® visualization tool, via a combination of word fragments, wildcard strings, and mathematical constructs, based on Hy’s law criteria and pattern of injury (R-value). These criteria excluded non-eligible cases from monthly line listings mined from the Argus safety database. The capabilities and limitations of these criteria were verified by comparing a manual review of all monthly cases with system-generated monthly listings over six months. Results: On an average, over a period of six months, the algorithm accurately identified 92% of DILI cases meeting established criteria. The automated process easily compared liver enzyme elevations with baseline values, reducing the screening time to under 15 minutes as opposed to multiple hours exhausted using a cognitively laborious, manual process. Limitations of the algorithm include its inability to identify cases associated with non-standard laboratory tests, naming conventions, and/or incomplete/incorrectly entered laboratory values. Conclusions: The newly developed multifactorial algorithm proved to be extremely useful in detecting potential DILI cases, while heightening the vigilance of the drug safety department. Additionally, the application of this algorithm may be useful in identifying a potential signal for DILI in drugs not yet known to cause liver injury (e.g., drugs in the initial phases of development). This algorithm also carries the potential for universal application, due to its product-agnostic data and keyword mining features. Plans for the tool include improving it into a fully automated application, thereby completely eliminating a manual screening process.

Keywords: automation, drug-induced liver injury, pharmacovigilance, post-marketing

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Authors: Mariam Shah

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‘Honour’ crime has commonly been perceived in the UK as being a ‘domestic violence’ related issue due to incidents perceived to take place within a domestic context, and commonly by familial perpetrators. The lack of differentiation between domestic violence and ‘honour’ related incidents has several negative implications. Firstly, the prevalence and extent of ‘honour’ related crime within the UK cannot be accurately quantified due to ‘honour’ incidents being classed statistically as domestic violence incidents. Secondly, lack of differentiation means that the negative stereotypical attitudes ascribed to domestic violence which has resulted in lower criminal conviction rates that are also impacting the conviction of perpetrators of ‘honour’ crime. Thirdly, ‘honour’ related crime is innately distinct from domestic violence due to the perpetrator’s resolute intent of cleansing perceived ‘shame’ in any way possible, often with the involvement and collusion of multiple perpetrators from within the family and/or community. Domestic violence is typically restricted to the ‘home’, but ‘honour’ crime can operate between national and international boundaries. This paper critically examines the current academic literature and concludes that the few similarities between domestic violence and ‘honour’ related crime are not sufficient to warrant identical treatment under UK criminal law. ‘Honour’ related crime is a distinct and stand-alone offence which should be recognised as such. The appropriate identification and treatment of ‘honour’ crime are crucial, particularly in light of the UK’s first ‘white’ honour killing which saw a young English woman murdered after being deemed to have brought ‘shame’ on her ex-boyfriend’s family. This incident highlights the possibility of ‘honour’ crime extending beyond its perceived ‘ethnic minority’ roots and becoming more of a ‘mainstream’ issue for the multi-cultural and multi-racial UK.

Keywords: differentiation, domestic violence, honour crime, United Kingdom

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Authors: Francesca Lombardi, Francesca Rosaria Augello, Benedetta Cinque, Maria Grazia Cifone, Paola Palumbo

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Glioblastoma multiforme (GBM) is a high-grade primary brain tumor refractory to current forms of treatment. The survival benefits of patients with GBM remain unsatisfactory due to the intrinsic or acquired resistance to temozolomide (TMZ), an alkylating agent, used as the first-line chemotherapeutic drug to treat GBM patients. Its cytotoxic effect is visualized by the induction of O6-methylguanine (O6MeG) within DNA. Cyclooxygenase-2 (COX-2), an inflammation-associated enzyme, has been implicated in tumorigenesis and progression of GBM, its inhibition shows anticancer activities. In the present study, it was verified if the combination of a COX-2 selective inhibitor, NS398, with TMZ could counteract the TMZ resistance. In particular, the effect of NS398 mixed with TMZ was investigated in the GBM TMZ-resistant cell line, T98G. Cells were pretreated with NS398 (100µM, 24 hours) and then exposed to TMZ alone (200µM), NS398 alone, or both for 72 hours, after which cell growth rate and cycle phases, as well as apoptosis level, were evaluated. Coadministration of NS398 and TMZ caused a significant decrease in cell growth and a progressive increase of dead cells detected by trypan blue staining. Moreover, a significant level of apoptotic cell percentage and alteration of cell cycle phases were observed in T98G treated with TMZ-NS398 combination when compared to untreated cells or TMZ-treated cells. TMZ-resistant tumors, as GBM, express elevated levels of DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). The mixture drastically reduced MGMT expression in the TMZ-resistant cell line T98G, known to express high levels of MGMT basically. Moreover, while TMZ alone did not influence the COX-2 protein expression, the combination successfully reduced it. In conclusion, these results demonstrated that NS398 enhanced the efficacy of TMZ through cell number reduction, apoptosis induction, and decreased MGMT levels, suggesting the ability of drug combination to reduce the chemoresistance. This drug combination deserves attention and could be considered as a promising therapeutic strategy for GBM patients.

Keywords: COX-2, COX-2 inhibitor, glioblastoma, NS398, T98G, temozolomide

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Authors: Christina Williams, Mehari Weldemariam, Ann M. Farese, Thomas J. MacVittie, Maureen A. Kane

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Radiation exposure results in dose-dependent and time-dependent multi-organ damage. Drug development of medical countermeasures (MCM) for radiation-induced injury occurs under the FDA Animal Rule because human efficacy studies are not ethical or feasible. The FDA Animal Rule requires the representation of both sexes and describes several uses for biomarkers in MCM drug development studies. Currently, MCMs are limited and there is no FDA-approved biomarker for any radiation injury. Sex as a variable is essential to identifying biomarkers and developing effective MCMs for acute radiation exposure (ARS) and delayed effects of acute radiation exposure (DEARE). These studies aim to address the death of information on sex differences that have not been determined by studies that included only male, single-sex cohorts. Studies have reported differences in radiosensitivity according to sex. As such, biomarker discovery for radiation-induced damage must consider sex as a variable. This study evaluated the plasma proteomic profile of Rhesus macaque non-human primates after different exposures and doses, as well as time points after radiation. Exposures and doses included total body irradiation between 5-7.5 Gy and partial body irradiation with 5% bone marrow sparing at 9, 9.5 and 10 Gy. Timepoints after irradiation included days 1, 3, 60, and 180, which encompassed both acute radiation syndromes and delayed effects of acute radiation exposure. Bottom-up proteomic analyses of plasma included equal numbers of males and females. In the control animals, few proteomic differences are observed between the sexes. In the irradiated animals, there are a few sex differences, with changes mostly consisting of proteins upregulated in the female animals. Multiple canonical pathways were upregulated in irradiated animals relative to the control animals when subjected to pathway analysis, but differential responses between the sexes are limited. These data provide critical baseline differences according to sex and establish sex differences in non-human primate models relevant to drug development of MCM under the FDA Animal Rule.

Keywords: ionizing radiation, sex differences, plasma proteomics, biomarker discovery

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Authors: Yu-Kai Ting, Jia-Ying Tu, Chung-Chun Hsiao

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New physical insights into the nonlinear Lorenz equations related to flow resistance is discussed in this work. The chaotic dynamics related to Lorenz equations has been studied in many papers, which is due to the sensitivity of Lorenz equations to initial conditions and parameter uncertainties. However, the physical implication arising from Lorenz equations about convectional motion attracts little attention in the relevant literature. Therefore, as a first step to understand the related fluid mechanics of convectional motion, this paper derives the Lorenz equations again with different forced conditions in the model. Simulation work of the modified Lorenz equations without the viscosity or buoyancy force is discussed. The time-domain simulation results may imply that the states of the Lorenz equations are related to certain flow speed and flow resistance. The flow speed of the underlying fluid system increases as the flow resistance reduces. This observation would be helpful to analyze the coupling effects of different fluid parameters in a convectional model in future work.

Keywords: Galerkin method, Lorenz equations, Navier-Stokes equations, convectional motion

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Authors: Prakash Singh

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In this exploratory qualitative case study, the voices of female teachers are captured that describe their fear of failure in coping with their daily anxieties, stresses, and tensions in their classrooms. When teachers are usually appointed, the curriculum forms the heart of all their professional obligations. The policy of quality and equality of education for all learners is a must as part of these deliberations, otherwise it would spell the inevitable failure for teachers. Yet, how often have teachers been asked whether they are happy during their professional tenure. Research affirms that this question is not a priority, seeing that the happiness of learners and the educational administrators enjoy precedence. Teachers are often subject to undue pressures and tensions because of environmental factors that extends beyond the curriculum. School violence, bullying, drug abuse, and gangsters are not uncommon to the school milieu, no matter where such schools can be located. In this case study, the voices of female teachers find space concerning their experiences of tobephobia (TBP). The questions that inevitably arise are: Are the educational authorities aware of the effects of TBP in education? What can be done to arrest and eliminate the debilitating effects of TBP? This exploratory study contributes to the growing concerns of TBP in education. It is therefore imperative that the effects of TBP on human resources in education must be accentuated so that meaningful solutions can be found to address challenging educational issues such as school violence, bullying, and drug abuse amongst learners.

Keywords: curriculum, female teachers, school violence, tobephobia

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Authors: Shan-Ying Wu, Sheng-Hui Lan, Xi-Zhang Lin, Ih-Jen Su, Ting-Fen Tsai, Chia-Jui Yen, Tsung-Hsueh Lu, Fu-Wen Liang, Huey-Jen Su, Chun-Li Su, Hsiao-Sheng Liu

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In hepatocelluar carcinoma (HCC), dysregulated expression of cyclin D1 and impaired autophagy has been reported separately. However, the relationship between them has not been explored. In this study, we demonstrated that autophagy was inversely correlated with cyclin D1 expression in 147 paired HCC patient specimens. HCC specimen with highly expression of cyclin D1 shows correlation with poor overall survival rate. Furthermore, induction of autophagy by amiodarone (antiarrhythmic drug) in Hep 3B cells, cyclin D1 was recruited into autophagosomes demonstrated by immune-gold labeling of cyclin D1 after extraction of autophagosomes. We further demonstrated that autophagy suppresses Hep 3B cell proliferation, and further analysis revealed that cell cycle was arrested at G1 phase. The interaction between LC3 (maker of autophagy) and cyclin D1 was increased after autophagy induction. In addition, ubiquitinated-cyclin D1 was also increased after autophagy induction, which is selectively degraded by autophagosome through binding with SQSTM1/p62 (an adaptor protein). In vivo study showed that amiodarone induced autophagy suppresses liver tumor formation in xenograft mouse and orthotopic rat model through decreasing cyclin D1 expression and inhibition of cell proliferation. Altogether, we reveal a novel mechanism that ubiquitinated cyclin D1 degraded by autophagic pathway by p62 and amiodarone is a promising drug for targeting cyclin D1 in liver cancer therapy.

Keywords: autophagy, cyclin D1, hepatocellular carcinoma, amiodarone

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Authors: A. Alyami, S. Christmas, K. Neeltje, G. Pollakis, B. Paxton, Z. Al-Bayati

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The Human leukocyte antigen-G (HLA-G) molecule plays an important role in immunomodulation. To date, 16 untranslated regions (UTR) HLA-G haplotypes have been previously defined by sequenced SNPs in the coding region. From these, UTR-1, UTR-2, UTR-3, UTR-4, UTR-5, UTR-6 and UTR-7 are the most frequent 3’UTR haplotypes at the global level. UTR-1 is associated with higher levels of soluble HLA-G and HLA-G expression, whereas UTR-5 and UTR-7 are linked with low levels of soluble HLA-G and HLA-G expression. Human immunodeficiency virus type 1 (HIV-1) infection results in the progressive loss of immune function in infected individuals. The virus escape mechanism typically includes T lymphocytes and NK cell recognition and lyses by classical HLA-A and B down-regulation, which has been associated with non-classical HLA-G molecule up-regulation, respectively. We evaluated the haplotypes of the HLA-G 3′ untranslated region frequencies observed in three HIV-1 groups from the Netherlands and their susceptibility to develop infection. The three groups are made up of mainly men who have sex with men (MSM), injection drug users (IDU) and a high-risk-seronegative (HRSN) group. DNA samples were amplified with published primers prior sequencing. According to our results, the low expresser frequencies show higher in HRSN compared to other groups. This is indicating that 3’UTR polymorphisms may be identified as potential prognostic biomarkers to determine susceptibility to HIV.

Keywords: Human leukocyte antigen-G (HLA-G) , men who have sex with men (MSM), injection drug users (IDU), high-risk-seronegative (HRSN) group, high-untranslated region (UTR)

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Authors: Lian Wu, Mervyn Merrilees

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Chronic Obstructive Pulmonary Disease (COPD) is a worldwide problem, characterized by irreversible and progressive airflow obstruction. In New Zealand, it is currently the 4th commonest cause of death and exacerbations of COPD are a frequent cause of admission to hospital. Serum levels of Clara cell secretory protein-16 (CC-16) are believed to represent Clara cell toxicity. More recently, CC-16 has been found to be associated with smoker COPD. It is produced almost exclusively by non-ciliated Clara cells in the airways, and its primary function is to protect the lungs against oxidative stress and carcinogenesis. After acute exposure to cigarette smoke, serum levels of CC-16 become elevated. CC16 is a potent natural immune-suppressor and anti-inflammatory agent. In vitro, CC16 inhibits both monocyte and polymorphonuclear neutrophils chemotaxis and phagocytosis. CC16 also inhibits fibroblast chemotaxis. However, the role of CC-16 in non-smoking related COPD is still not clear. In this study, we investigated serum CC-16 levels in non-smoking related COPD. Methods: We compared non-smoker patients with COPD (FEV1<60% of predicted, FEV1/FVC <0.7, n=100) and individuals with normal lung function FEV1≥ 80% of predicted and FEV1/FVC≥ 0.7, n=80). All subjects had no smoking history. CC-16 was measured by ELISA. Results and conclusion: Serum CC-16 levels are reduced in individuals with non-smoking related COPD, and there is a weak correlation with disease severity in non-smoking related COPD group compared to non-smoker controls.

Keywords: COPD, CC-16, ELISA, non-smoking-related COPD

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Authors: E. Batista, R. Mendes, A. Furtado, M. C. Ferreira, I. Godinho, J. A. Sousa, M. Alvares, R. Martins

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Syringe pumps are commonly used for drug delivery in hospitals and clinical environments. These instruments are critical in neonatology and oncology, where any variation in the flow rate and drug dosing quantity can lead to severe incidents and even death of the patient. Therefore it is very important to determine the accuracy and precision of these devices using the suitable calibration methods. The Volume Laboratory of the Portuguese Institute for Quality (LVC/IPQ) uses two different methods to calibrate syringe pumps from 16 nL/min up to 20 mL/min. The Interferometric method uses an interferometer to monitor the distance travelled by a pusher block of the syringe pump in order to determine the flow rate. Therefore, knowing the internal diameter of the syringe with very high precision, the travelled distance, and the time needed for that travelled distance, it was possible to calculate the flow rate of the fluid inside the syringe and its uncertainty. As an alternative to the gravimetric and the interferometric method, a methodology based on the application of optical technology was also developed to measure flow rates. Mainly this method relies on measuring the increase of volume of a drop over time. The objective of this work is to compare the results of the calibration of two syringe pumps using the different methodologies described above. The obtained results were consistent for the three methods used. The uncertainties values were very similar for all the three methods, being higher for the optical drop method due to setup limitations.

Keywords: calibration, flow, interferometry, syringe pump, uncertainty

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Authors: Tan Hui Ying Renee, Stella Rizalina Sasha, Farah Safdar Husain

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Introduction: Menopause Hormone Therapy (MHT) is an effective drug indicated for the treatment of menopausal symptoms and as replacement therapy in women who undergo premature menopause. In 2020, less than 8.8% of perimenopausal Singaporean women are on hormonal therapy, as compared to the Western population, where up to 50% may be on MHT. Factors associated with MHT utilization have been studied from patient characteristics, but the impact of locally prescribing physicians resulting in low MHT utilization has yet to be evaluated. The aim of the study is to determine the level of knowledge physicians in the Obstetrics and Gynaecology specialty have and their attitudes toward MHT. We believe that knowledge of MHT is lacking and that negative attitudes towards MHT may influence its use and undermine the benefits MHT may have for women. This paper is a part of a larger study on Singaporean physicians’ knowledge and attitudes towards MHT. Methods: This is a cross-sectional study intended to assess the knowledge and attitudes of physicians toward Menopausal Hormone Therapy. An anonymous questionnaire was disseminated via institutional internal circulations to optimize reach to physicians who may prescribe MHT, particularly in the fields of Gynaecology, Family Medicine and Endocrinology. Responses were completed voluntarily. Physicians had the option for each question to declare that they were ‘unsure’ or that the question was ‘beyond their expertise’. 21 knowledge questions tested factual recall on indications, contraindications, and risks of MHT. The remaining 6 questions were clinical scenarios crafted with the intention of testing specific principles related to the use of MHT. These questions received face validation from experts in the field. 198 responses were collected, 79 of which were from physicians in the Obstetrics and Gynaecology specialty. The data will be statistically analyzed to investigate areas that can be improved to increase the overall benefits of MHT for the Singaporean population. Results: Preliminary results show that the prevailing factors that limit Singaporean gynecologists and obstetricians from prescribing MHT are a lack of knowledge of MHT and a lack of confidence in prescribing MHT. Risks and indications of MHT were not well known by many physicians, with the majority of the questions having more than 25% incorrect and ‘unsure’ as their reply. The clinical scenario questions revealed significant shortcomings in knowledge on how to navigate real-life challenges in MHT use, with 2 of 6 questions with more than 50% incorrect or ‘beyond their expertise’ as their reply. The portion of the questionnaire that investigated the attitudes of physicians showed that though a large majority believed MHT to be an effective drug, only 40.5% were confident in prescribing it. Conclusion: Physicians in the Obstetrics and Gynaecology specialty lack knowledge and confidence in MHT. Therefore, it is imperative to formulate solutions on both the individual and institutional levels to fill these gaps and ensure that MHT is used appropriately and prescribed to the patients who need it.

Keywords: menopause, menopause hormone therapy, physician factors, obstetrics and gynecology, menopausal symptoms, Singapore

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Authors: Samah Lakehal, A. Meliani, F. Z. Benrebiha, C. Chaouia

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In the last few years, due to the misuse of antibiotics and an increasing incidence of immunodeficiency-related diseases, the development of microbial drug resistance has become more and more of a pressing problem. Recently, natural products from medicinal plants represent a fertile ground for the development of novel antibacterial agents. Plants essential oils have come more into the focus of phytomedicine. The present study describes antimicrobial activity of Rosmarinus officinalis L. essential oil known medicinally for its powerful antibacterial properties. The essential oil of rosemary obtained by hydrodistillation (using Clevenger type apparatus) growing in Algeria (Djelfa city of south Algeria) was investigated by GC-MS. The essential oil yield of the study was 1.4 %. The major components were found to be camphor, camphene, 1,8-cineole. The essential oil has been tested for antimicrobial activity against eight bacteria (Gram-negative and Gram-positive), and three fungi including Candida albicans. Inhibition of growth was tested by the agar diffusion method based on the determination of the diameter of inhibition. The oil was found to have significant antibacterial activity and therefore can be used as a natural antimicrobial agent for the treatment of several infectious diseases caused by those germs, which have developed resistance to antibiotics.

Keywords: antimicrobial activity, Rosmarinus officinalis L., essential oils, GC/MS, camphor

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Authors: R. H. Bustos, L. Martinez, J. García, F. Suárez

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MRP1 (Multi-drug resistance associated protein 1) and MRP2 (Multi-drug resistance associated protein 2) are two proteins belonging to the transporters of ABC (ATP-Binding Cassette). These transporter proteins are involved in the efflux of several biological drugs and xenobiotic and also in multiple physiological, pathological and pharmacological processes. Evidence has been found that there is a correlation among different polymorphisms found and their clinical implication in the resistance to antiepileptic, chemotherapy and anti-infectious drugs. In our study, exonic regions of MRP1/ABCC1 y MRP2/ABCC2 were studied in the Colombian population, specifically in the region of the central Savannah (Cundinamarca) to determinate SNP (Single Nucleotide Polymorphisms) and determinate its allele frequency and its genomics frequency. Results showed that for our population, SNP are found that have been previously reported for MRP1/ABCC1 (rs200647436, rs200624910, rs150214567) as well as for MRP2/ABCC2 (rs2273697, rs3740066, rs142573385, rs17216212). In addition, 13 new SNP were identified. Evidences show an important clinic correlation for polymorphisms rs3740066 and rs2273697. The study object population displays genetic variability as compared to the one reported in other populations.

Keywords: ATP-binding cassette (ABCC), Colombian population, multidrug-resistance protein (MRP), pharmacogenetic, single nucleotide polymorphism (SNP)

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Authors: Veronika Sharok

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Research relevance on psychological determinants of risky behaviors is caused by high prevalence of such behaviors, particularly among youth. Risky sexual behavior, including unprotected and casual sex, frequent change of sexual partners, drug and alcohol use lead to negative social consequences and contribute to the spread of HIV infection and other sexually transmitted diseases. Data were obtained from 302 respondents aged 15-35 which were divided into 3 empirical groups: persons prone to risky sexual behavior, drug users and alcohol users; and 3 control groups: the individuals who are not prone to risky sexual behavior, persons who do not use drugs and the respondents who do not use alcohol. For processing, we used the following methods: Qualitative method for nominative data (Chi-squared test) and quantitative methods for metric data (student's t-test, Fisher's F-test, Pearson's r correlation test). Statistical processing was performed using Statistica 6.0 software. The study identifies two groups of factors that prevent risky behaviors. Internal factors, which include the moral and value attitudes; significance of existential values: love, life, self-actualization and search for the meaning of life; understanding independence as a responsibility for the freedom and ability to get attached to someone or something up to a point when this relationship starts restricting the freedom and becomes vital; awareness of risky behaviors as dangerous for the person and for others; self-acknowledgement. External factors (prevent risky behaviors in case of absence of the internal ones): absence of risky behaviors among friends and relatives; socio-demographic characteristics (middle class, marital status); awareness about the negative consequences of risky behaviors; inaccessibility to psychoactive substances. These factors are common for proneness to each type of risky behavior, because it usually caused by the same reasons. It should be noted that if prevention of risky behavior is based only on elimination of external factors, it is not as effective as it may be if we pay more attention to internal factors. The results obtained in the study can be used to develop training programs and activities for prevention of risky behaviors, for using values preventing such behaviors and promoting healthy lifestyle.

Keywords: existential values, prevention, psychological features, risky behavior

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Authors: Emad Heydarnia, Aref Sepasi, Nika Asefi, Sara Khakshournia, Javad Mohammadnejad

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Background: Despite breakthrough therapeutics in breast cancer, it is one of the main causes of mortality among women worldwide. Thus, drug therapies for treating breast cancer have recently been developed by scientists. Metformin and Sorafenib are well-known therapeutic in breast cancer. In the present study, we combined Sorafenib and PCL-sorafenib with metformin to improve drug absorption and promote therapeutic efficiency. Methods: The MCF-7 cells were treated with Metformin, Sorafenib, or PCL-sorafenib. The growth inhibitory effect of these drugs and cell viability were assessed using MTT and flow cytometry assays, respectively. The expression of targeted genes involved in cell proliferation, signaling, and the cell cycle was measured by Real-time PCR. Results: The results showed that MCF-7 cells treated with Metformin/Sorafenib and PCL-sorafenib/Metformin co-treatment contributed to 50% viability compared to untreated group. Moreover, PI and Annexin V staining tests showed that the cells viability for Metformin/Sorafenib and PCL-sorafenib/Metformin was 38% and 17%, respectively. Furthermore, Sorafenib/Metformin and PCL-sorafenib/Metformin leads to p53 gene expression increase by which they can increase ROS, thereby decreasing GPX4 gene expression. In addition, they affected the expression of BCL2, and BAX genes and altered the cell cycle. Conclusion: Together, the combination of PCL-sorafenib/Metformin and Sorafenib/Metformin increased Sorafenib absorption at lower doses and also leads to apoptosis and oxidative stress increases in MCF-7 cells.

Keywords: breast cancer, metformin, nanotechnology, sorafenib

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Authors: Kai-Cheng Hsu, Tzu-Ying Sung, Jinn-Moon Yang

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Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Although several drugs have been developed to treat colorectal cancer, such as Regorafenib and 5-FU, their efficacy is often limited by the development of drug resistance. Therefore, development of new drugs with new scaffolds is necessary to treat CRC. Here, we used site-moiety maps to identify inhibitors against PIM1, LIMK1, SRC, and mTOR, which are often overexpressed in CRC. A site-moiety map represents physicochemical properties and moiety preferences of a binding site through anchors. An anchor contains three elements: (1) conserved interacting residues of a binding pocket; (2) moiety preference of the binding pocket; and (3) the type (e.g., hydrogen-bonding or van der Waals interactions) of interaction between the moieties and the binding pocket. Then, we performed a structure-based virtual screening of ~260,000 compounds and selected compound candidates with high site-moiety map scores for bioassays. Among these candidates, compound 1 and compound 2 inhibited the growth of CRC cells with IC50 values of <10 μM. The experimental result of enzyme-based assays indicated that compound 1 is a dual inhibitor against PIM1 (IC50 6 μM) and LIMK1(IC50 11 μM). Compound 2 was predicted as a SRC inhibitor and will be further validated. The compounds inhibited different protein targets compared to the current drugs. We believe that the compounds provide a starting point to design new drugs for CRC treatment.

Keywords: colorectal cancer, drug discovery, site-moiety map, virtual screening, PIM1, LIMK1

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Authors: M. A. T. AlSudairi, T. G. K. Vasista

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The concept of social media is becoming the top of the agenda for many business executives and public sector executives today. Decision makers as well as consultants, try to identify ways in which firms and enterprises can make profitable use of social media and network related applications such as Wikipedia, Face book, YouTube, Google+, Twitter. While it is fun and useful to participating in this media and network for achieving the communication effectively and efficiently, semantic and sentiment analysis and interpretation becomes a crucial issue. So, the objective of this paper is to provide literature review on social media, network and related technology related to semantics and sentiment or opinion analysis covering business and governance perspectives. In this regard, a case study on the use and adoption of Social media in Saudi Arabia has been discussed. It is concluded that semantic web technology play a significant role in analyzing the social networks and social media content for extracting the interpretational knowledge towards strategic decision support.

Keywords: CRASP methodology, formative assessment, literature review, semantic web services, social media, social networks

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Authors: KangQi Jin

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School-Related Gender-Based Violence (SRGBV) seriously impacts the victim's physical and mental health and academic and employment prospects. Due to the lack of protective policies for sexual minority students in mainland China at present, the well-being of those students in China is seriously endangered by SRGBV, and their physical and mental health is at great risk. By analyzing the current situation of stigmatization of sexual minority students and the harm brought to them by gender violence, this study proposes some strategies to reduce SRGBV on sexual minorities. First, the nation should set laws to protect the rights and interests of sexual minorities, and second, universities should make multifaceted efforts to reduce these violent phenomena. The violence experienced by students of sexual minorities has a crucial impact on their future physiology and psychology, and through the research, in this paper, the author hope can provide suggestions for scholars who try to study related fields in the future.

Keywords: sexual minority, school-related gender-based violence, response, strategies

Procedia PDF Downloads 105