Search results for: drug and alcohol prevention
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3897

Search results for: drug and alcohol prevention

2787 Still a Man’s World? Rape Myth Acceptance, Attitudes Towards Women and Traditional Male Gender Role Beliefs in a Sample of British Military Veterans

Authors: Jessica Beck

Abstract:

Despite efforts to address the issue through prevention and education, sexual assault remains an issue within the military. Rape supportive beliefs have been identified as a risk factor linked to sexually aggressive and coercive behaviours. Rape myth acceptance is part of a wider cognitive framework of attitudes which perpetuate negative sociocultural norms about the male role. Notwithstanding the established links between rape myth acceptance, attitudinal variables, and rape proclivity, relatively little research has been conducted with military samples. In this study, 151 British military veterans completed an online survey measuring their rape myth acceptance, attitudes towards women, belief in male role norms and basic personality traits. Consistent with previous research, male veterans had higher levels of rape myth acceptance, more negative attitudes towards women, and subscribed to more traditional notions of masculinity. The types of myths endorsed also varied by gender, with male veterans significantly more likely to blame rape victims or believe women regularly lie about being raped. A relationship between rape myth acceptance, negative attitudes towards women, and adherence to male norms was found, which explained a significant proportion of the variance in rape myth acceptance. Implications for sexual assault prevention programmes are discussed.

Keywords: rape myths, rape myth acceptance, military sexual assault, sexual assault beliefs

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2786 Investigation of Carbapenem-Resistant Genes in Acinetobacter spp. Isolated from Patients at Tertiary Health Care Center, Northeastern Thailand

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

Abstract:

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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2785 Traumatic Spinal Cord Injury in King Fahd Medical City: An Epidemiological Study

Authors: Saeed Alshahri

Abstract:

Introduction: Our study aims to estimate the characteristics & causes of TSCI at King Fahad Medical City (KFMC) in Riyadh city in order to hypothesize strategy for primary prevention of traumatic spinal cord injury. Method: Cross-sectional, retrospective study was conducted on all TSCI patients who aged 14 and above and who were admitted to rehabilitation center of King Fahad Medical City from January 2012 to December 2015. Furthermore, a descriptive analysis was conducted while considering factors including age, gender, marital status, educational level and causes of injury and characteristics of injury. Results: Total of 216 patients were admitted during this period, mean age was 28.94, majority of patients were male (86.5%), 71.7% of total patients were high school level of education or less, 68% were single, RTA was the main cause with 90.7% and the main result of TSCI was complete paraplegia 37%. Furthermore, statistically, we found that males are at a low risk of having incomplete paraplegia compared to female (p = 0.035, RRR=0.35). Conclusion: The rate of TSCI related to RTA has increased in Saudi Arabia in previous years despite the government’s efforts to decrease RTA. It’s clear that we need TSCI registry data developed on the basis of international data standards to have a clear idea about the exact etiology of TSCI in Saudi Arabia. This will assist in planning for primary prevention.

Keywords: traumatic spinal cord injury, road traffic accident, Saudi Arabia, spinal cord injury

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2784 Sitagliptin-AntiCD4 Mab Conjugated T Cell Targeting Therapy for the Effective Treatment of Type I Diabetes

Authors: T. Mahesh, M. K. Samanta

Abstract:

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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2783 Prospective Randomized Trial of Na/K Citrate for the Prevention of Contrast-Induced Nephropathy in High-Risk Patients

Authors: Leili Iranirad, Mohammad Saleh Sadeghi, Seyed Fakhreddin Hejazi, Negar Vakili Razlighi

Abstract:

Objective: Contrast-induced nephropathy (CIN) or contrast-induced acute kidney injury (CI-AKI) is an unknown acute kidney injury (AKI) occurring after exposure to contrast media (CM). Contrast agents are most often used for diagnostic procedures or therapeutic angiographic interventions. Recently, Na/K citrate as a urine alkalinization has been evaluated for the prevention of CIN. We conducted this experiment to evaluate the efficiency of Na/K citrate on CIN in high-risk patients treated with cardiac catheterization. Methods: A prospective randomized clinical trial was conducted on 400 patients having moderate to high-risk factors for CIN treated with elective percutaneous coronary intervention (PCI) and were assigned randomly to the control group or the Na/K citrate group. The Na/K citrate group (n=200) received 5 g Na/K citrate solution, which was diluted in 200 mL water two h before and four hours after the first administration and intravenous hydration for two h prior to and six h after the procedure, while the control group (n=200) only received intravenous hydration. Serum creatinine (SCr) was calculated prior to the contrast exposure and after 48 h. CIN was described as a 25% increase in creatinine of serum (SCr) or >0.5 mg/dl 48 h after contrast administration. Results: CIN was observed in 33 patients (16.5%) in the control group and in 6 patients (3%) in the Na/K citrate group. A significant variation was recorded in the CIN incidence between the two groups 48 h after the radiocontrast agent administration (p < 0.001). Conclusion: Our results show that Na/K citrate is useful and substantially reduces the incidence of CIN.

Keywords: contrast media, citrate, PCI

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2782 Deep Injection Wells for Flood Prevention and Groundwater Management

Authors: Mohammad R. Jafari, Francois G. Bernardeau

Abstract:

With its arid climate, Qatar experiences low annual rainfall, intense storms, and high evaporation rates. However, the fast-paced rate of infrastructure development in the capital city of Doha has led to recurring instances of surface water flooding as well as rising groundwater levels. Public Work Authority (PWA/ASHGHAL) has implemented an approach to collect and discharge the flood water into a) positive gravity systems; b) Emergency Flooding Area (EFA) – Evaporation, Infiltration or Storage off-site using tankers; and c) Discharge to deep injection wells. As part of the flood prevention scheme, 21 deep injection wells have been constructed to discharge the collected surface and groundwater table in Doha city. These injection wells function as an alternative in localities that do not possess either positive gravity systems or downstream networks that can accommodate additional loads. These injection wells are 400-m deep and are constructed in a complex karstic subsurface condition with large cavities. The injection well system will discharge collected groundwater and storm surface runoff into the permeable Umm Er Radhuma Formation, which is an aquifer present throughout the Persian Gulf Region. The Umm Er Radhuma formation contains saline water that is not being used for water supply. The injection zone is separated by an impervious gypsum formation which acts as a barrier between upper and lower aquifer. State of the art drilling, grouting, and geophysical techniques have been implemented in construction of the wells to assure that the shallow aquifer would not be contaminated and impacted by injected water. Injection and pumping tests were performed to evaluate injection well functionality (injectability). The results of these tests indicated that majority of the wells can accept injection rate of 200 to 300 m3 /h (56 to 83 l/s) under gravity with average value of 250 m3 /h (70 l/s) compared to design value of 50 l/s. This paper presents design and construction process and issues associated with these injection wells, performing injection/pumping tests to determine capacity and effectiveness of the injection wells, the detailed design of collection system and conveying system into the injection wells, and the operation and maintenance process. This system is completed now and is under operation, and therefore, construction of injection wells is an effective option for flood control.

Keywords: deep injection well, flood prevention scheme, geophysical tests, pumping and injection tests, wellhead assembly

Procedia PDF Downloads 103
2781 Role of DatScan in the Diagnosis of Parkinson's Disease

Authors: Shraddha Gopal, Jayam Lazarus

Abstract:

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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2780 A Multifactorial Algorithm to Automate Screening of Drug-Induced Liver Injury Cases in Clinical and Post-Marketing Settings

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

Abstract:

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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2779 COX-2 Inhibitor NS398 Counteracts Chemoresistance to Temozolomide in T98G Glioblastoma Cell Line

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

Abstract:

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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2778 Proteomic Evaluation of Sex Differences in the Plasma of Non-human Primates Exposed to Ionizing Radiation for Biomarker Discovery

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

Abstract:

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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2777 Cultural Collisions, Ethics and HIV: On Local Values in a Globalized Medical World

Authors: Norbert W. Paul

Abstract:

In 1988, parts of the scientific community still heralded findings to support that AIDS was likely to remain largely a ‘gay disease’. The value-ladden terminology of some of the articles suggested that rectum and fragile urethra are not sufficiently robust to provide a barrier against infectious fluids, especially body fluids contaminated with HIV while the female vagina, would provide natural protection against injuries and trauma facilitating HIV-infection. Anal sexual intercourse was constituted not only as dangerous but also as unnatural practice, while penile-vaginal intercourse would follow natural design and thus be relatively safe practice minimizing the risk of HIV. Statements like the latter were not uncommon in the early times of HIV/AIDS and contributed to captious certainties and an underestimation of heterosexual risks. Pseudo-scientific discourses on the origin of HIV were linked to local and global health politics in the 1980ies. The pathways of infection were related to normative concepts like deviant, subcultural behavior, cultural otherness, and guilt used to target, tag and separate specific groups at risk from the ‘normal’ population. Controlling populations at risk became the top item on the agenda rather than controlling modes of transmission and the virus. Hence, the Thai strategy to cope with HIV/AIDS by acknowledging social and sexual practices as they were – not as they were imagined – has become a role model for successful prevention in the highly scandalized realm of sexually transmitted disease. By accepting the globalized character of local HIV-risk and projecting the risk onto populations which are neither particularly vocal groups nor vested with the means to strive for health and justice Thailand managed to culturally implement knowledge-based tools of prevention. This paper argues, that pertinent cultural collisions regarding our strategies to cope with HIV/AIDS are deeply rooted in misconceptions, misreadings and scandalizations brought about in the early history of HIV in the 1980ties. The Thai strategy is used to demonstrate how local values can be balanced against globalized health risk and used to effectuated prevention by which knowledge and norms are translated into local practices. Issues of global health and injustice will be addressed in the final part of the paper dealing with the achievability of health as a human right.

Keywords: bioethics, HIV, global health, justice

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2776 Investigation and Monitoring Method of Vector Density in Kaohsiung City

Authors: Chiu-Wen Chang, I-Yun Chang, Wei-Ting Chen, Hui-Ping Ho, Chao-Ying Pan, Joh-Jong Huang

Abstract:

Dengue is a ‘community disease’ or ‘environmental disease’, as long as the environment exist suitable container (including natural and artificial) for mosquito breeding, once the virus invade will lead to the dengue epidemic. Surveillance of vector density is critical to effective infectious disease control and play an important role in monitoring the dynamics of mosquitoes in community, such as mosquito species, density, distribution area. The objective of this study was to examine the relationship in vector density survey (Breteau index, Adult index, House index, Container index, and Larvae index) form 2014 to 2016 in Kaohsiung City and evaluate the effects of introducing the Breeding Elimination and Appraisal Team (hereinafter referred to as BEAT) as an intervention measure on eliminating dengue vector breeding site started from May 2016. BEAT were performed on people who were suspected of contracting dengue fever, a surrounding area measuring 50 meters by 50 meters was demarcated as the emergency prevention and treatment zone. BEAT would perform weekly vector mosquito inspections and vector mosquito inspections in regions with a high Gravitrap index and assign a risk assessment index to each region. These indices as well as the prevention and treatment results were immediately reported to epidemic prevention-related units every week. The results indicated that, vector indices from 2014 to 2016 showed no statistically significant differences in the Breteau index, adult index, and house index (p > 0.05) but statistically significant differences in the container index and larvae index (p <0.05). After executing the integrated elimination work, container index and larvae index are statistically significant different from 2014 to 2016 in the (p < 0.05). A post hoc test indicated that the container index of 2014 (M = 12.793) was significantly higher than that of 2016 (M = 7.631), and that the larvae index of 2015 (M = 34.065) was significantly lower than that of 2014 (M = 66.867). The results revealed that effective vector density surveillance could highlight the focus breeding site and then implement the immediate control action (BEAT), which successfully decreased the vector density and the risk of dengue epidemic.

Keywords: Breteau index, dengue control, monitoring method, vector density

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2775 The Nigeria Police Force: Human Resources Management Issues and the Community Policing Policy Transfer

Authors: Aminu Musa Audu

Abstract:

This paper examines the human resources management issues of the Nigeria Police and how it is impacting the community policing policy transfer. Nigeria Police Force is the organisation in the country with the constitutional responsibility of maintaining law and order. The high level of crime and other forms of insecurity called for the introduction of ‘police-community partnership’ strategy in 2003. The trend of events has suggested that the effort is not yielding result, partly because the police in Nigeria are facing human resources management challenges. For instance, the prospective candidates for the police jobs are usually not vetted a situation which provides the possibility of recruiting persons of low academic background and questionable character, or even criminal records. Moreover, the existing training, development infrastructure and other logistics for the job of policing are not in good condition. Consequently, the implementation of the ‘community policing’ policy for crime prevention and control in Nigeria stands to suffer setbacks. Adopting qualitative methods and with focus groups discussions and individual in-depth interviews for data collections, the findings from the views and perspectives of the participants were suggestive of poor handlings of human resources management of the Nigeria police organisation and with negative effect on the implementation of community policing policy. The paper therefore recommends that a total overhaul of the human resources component of the police organisation is necessary in the community policing policy transfer process for crime prevention and control in Nigeria.

Keywords: Nigeria Police Force, community policing policy transfer, human resources management, police-community partnership

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2774 Automated Monitoring System to Support Investigation of Contributing Factors of Work-Related Disorders and Accidents

Authors: Erika R. Chambriard, Sandro C. Izidoro, Davidson P. Mendes, Douglas E. V. Pires

Abstract:

Work-related illnesses and disorders have been a constant aspect of work. Although their nature has changed over time, from musculoskeletal disorders to illnesses related to psychosocial aspects of work, its impact on the life of workers remains significant. Despite significant efforts worldwide to protect workers, the disparity between changes in work legislation and actual benefit for workers’ health has been creating a significant economic burden for social security and health systems around the world. In this context, this study aims to propose, test and validate a modular prototype that allows for work environmental aspects to be assessed, monitored and better controlled. The main focus is also to provide a historical record of working conditions and the means for workers to obtain comprehensible and useful information regarding their work environment and legal limits of occupational exposure to different types of environmental variables, as means to improve prevention of work-related accidents and disorders. We show the developed prototype provides useful and accurate information regarding the work environmental conditions, validating them with standard occupational hygiene equipment. We believe the proposed prototype is a cost-effective and adequate approach to work environment monitoring that could help elucidate the links between work and occupational illnesses, and that different industry sectors, as well as developing countries, could benefit from its capabilities.

Keywords: Arduino prototyping, occupational health and hygiene, work environment, work-related disorders prevention

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2773 Voices of Fear: A Case Study Of Tobephobia Experienced by Female Teachers

Authors: Prakash Singh

Abstract:

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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2772 Autophagy Regulates Human Hepatocellular Carcinoma Tumorigenesis through Selective Degradation of Cyclin D1

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

Abstract:

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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2771 Haplotypes of the Human Leukocyte Antigen-G Different HIV-1 Groups from the Netherlands

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

Abstract:

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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2770 Adverse Childhood Experiences and the Sense of Effectiveness and Coping with Emotions among Adolescents Taking Drugs

Authors: Monika Szpringer, Aneta Pawlinska

Abstract:

Adverse childhood experiences are linked to various types of health and adapt problems at different stages of life. They include various types of abuse, neglect, and dysfunctional environment. They have an unfavorable impact on the development of a child and his future functioning in society. Adolescents who were exposed to bad treatment may suffer from health problems during adulthood, like chronic diseases, psychological disorders, drug addiction, and suicide attempts. Objective: The aim of the project is to assess the relationship between adverse childhood experiences and the sense of efficacy and coping with emotions among teenagers aged 16-18 taking drugs. Material And Methods: The research was carried out in the period from March to December 2018 in Mazowieckie, Świętokrzyskie, Łódzkie, and Lubelskie Voivodship. The group consisted of 600 people aged 16-18 (M=16,58; SD=0, 78), men (63,2%) aged 16-18 (M=16,60;SD= 0,78) and women (35,5%) aged 16-18 (M16,55;SD=0,79). Participants included residents from Youth Educational Centers and Youth Sociotherapy Centers. Each participant filled in Author's Questionnaire, Adverse Childhood Questionnaire, then Courtland Emotional Control Scale-CECS and Generalized Self Efficacy Scale-GSES. Results and conclusions: The most common adverse experiences, according to teenagers, were family abuse, divorce/separation/parent's death, overuse of alcohol or drugs by an inmate, and emotional neglect. Adolescents who suffered from five to twelve adverse experiences had a higher level of depression's control. Adverse childhood experiences have an importance for the level of anger and depression's control among teenagers taking drugs. The greatest importance of the level of anger's control has emotional neglect. A higher level of emotional neglect is linked to a lower ability to control anger. The greatest importance of the level of depression's control has physical abuse and emotional neglect. The higher physical abuse during childhood, and the higher frequency of emotional neglect, the bigger the depression's control. The sense of efficacy in the group of people who suffered from one to four adverse experiences is close to the sense of efficacy that suffered people from five to twelve adverse experiences. The most important factor lowering the sense of one's efficacy was the intensification of sexual abuse. It was confirmed that the intensification and frequency of adverse childhood experiences were higher among women than men. Women also characterized lower anger control and greater depression's control. The authors’ own analyses confirmed the relationship between adverse childhood experiences and the sense of efficacy and coping with emotions among teenagers aged 16-18 taking drugs.

Keywords: adolescences, adverse childhood experiences, coping with emotions, drugs

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2769 Children Beliefs about Illness, Treatments and Vaccines after the Experience of Covid 19 Pandemic

Authors: Margarida Maria Cabugueira Csutódio dos Santos, Joana Filipa Pintéus Pereira

Abstract:

The way children understand the concept of health and illness influences their reaction in contexts where these concepts are present (e.g.,illness; vaccination). The recognition of the importance of children's beliefs/representations about health and disease has led to the development of models that seek to explain the development process of these concepts. In the construction of their representations, children are influenced not only by their cognitive competence but also by their life experiences. In the last 3 years, children have experienced a pandemic health crisis that has exposed them to anomalous and stressful situations. Objective: the aim of this study was (1) to identify children’s representations about disease (including symptoms, causes, control/treatment) and prevention (including health procedures and vaccines) and (2) whether COVID19 is mentioned and influences their representations. Methodology: a qualitative study in which 67 children with 7 to 10 years old (mean 8,8) participated. A semi-structured interview was used following the Bibace and Walsh model, focusing on the representation of the disease and its prevention. Results show a marked influence of the lived experience with regard to causes of the disease, disease control and treatment, and adherence to vaccination. Age-dependent differences were found with older children being able to talk about illness and contamination process and younger displaying more basic, concrete and rigid representations. Conclusions: The results of this study bring clues to the adequacy of communication with the child in the context of health and illness and discriminately in a future health pandemic crisis.

Keywords: childen, health beliefs, pediatrics, covid19, vaccines

Procedia PDF Downloads 69
2768 Calibration of Syringe Pumps Using Interferometry and Optical Methods

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

Abstract:

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

Procedia PDF Downloads 93
2767 Partial Replacement of GGBS in Concrete for Prevention of Natural Resources

Authors: M. Murmu, Govardhan, J. Satya Eswari

Abstract:

Concrete is the most common and widely used building material. Concrete is basically made of aggregates, both fine and coarse, glued by a cement paste which is made of cement and water. Each one of these constituents of concrete has a negative environmental impact and gives rise to different sustainability issues. The current concrete construction practice is unsustainable because, not only it consumes enormous quantities of stones, sand, and drinking water, but also one billion tons a year of cement, which is not an environment friendly material. Preventing the reduction of natural resources and enhancing the usage of waste materials has become a challenge to the scientist and engineers. A number of studies have been conducted concerning the protection of natural resources, prevention of environmental pollution and contribution to the economy by using this waste material. This paper outlines the influence of Ground Granulated Blast furnace Slag (GGBS) as partial replacement of fine aggregate on mechanical properties of concrete. The strength of concrete is determined having OPC binder, replaced the fine aggregate with15%, 30%, 45% respectively. For this purpose, characteristics concrete mix of M25 with partial replacement of cement with GGBS is used and the strength of concrete cubes and cylinder have determined. The strength of concrete specimens has been compared with the reference specimen. Also X-ray diffraction (XRD) and scanning electron microscope (SEM) tests have been performed to examine the hydration products and the microstructure of the tested specimens. A correlation has been established between the developmental strength concrete with and without GGBS through analysis of hydration products and the microstructure.

Keywords: GGBS, sand, concrete, workability

Procedia PDF Downloads 484
2766 Aggressive Behavior Prevention: The Effect of Peace Education and Media Literacy towards Student's Understanding about Aggression

Authors: Dadang Gunawan, I. Dewa Ketut Kertawidana, Lufthi Noorfitriyani

Abstract:

For the last 5 years, there is the never-ending violent act and increased cases regarding aggressive behavior among high school students in Bogor, Indonesia. Those cases caused harm to many people, even death, and lead to the continuation circle of violence. This research was conducted to evaluate the effect of using peace education and media literacy in enhancing student’s understanding about aggression, as an effort to prevent aggressive behavior. In terms of methodology, this research was done by quasi-experiment with one group pretest and post-test design. A number of 38 students who were at risk of aggressive behavior from 3 vocational high school were involved to receive a 10 learning session about peace and media literacy. The aggression questionnaire was used to identify participants, supported by student’s record in school. To collect data, the questionnaire for measuring understanding about aggression has been developed and was used after the validity and reliability of this questionnaire tested. Post-test was carried out after the session ended. Data were analyzed using t-test. The finding result showed that the mean score of student’s understanding of aggression was increased, therefore learning session of peace education and media literacy is significantly effective to enhance student’s understanding of aggression. It also showed a meaningful difference of understanding between male and female student’s whereas female students have a better understanding of aggression.

Keywords: aggressive behavior prevention, aggression, media literacy, peace education, peacebuilding

Procedia PDF Downloads 167
2765 New Environmental Culture in Algeria: Eco Design

Authors: S. Tireche, A. Tairi abdelaziz

Abstract:

Environmental damage has increased steadily in recent decades: Depletion of natural resources, destruction of the ozone layer, greenhouse effect, degradation of the quality of life, land use etc. New terms have emerged as: "Prevention rather than cure" or "polluter pays" falls within the principles of common sense, their practical implementation still remains fragmented. Among the avenues to be explored, one of the most promising is certainly one that focuses on product design. Indeed, where better than during the design phase, can reduce the source of future impacts on the environment? What choices or those of design, they influence more on the environmental characteristics of products? The most currently recognized at the international level is the analysis of the life cycle (LCA) and Life Cycle Assessment, subject to International Standardization (ISO 14040-14043). LCA provides scientific and objective assessment of potential impacts of the product or service, considering its entire life cycle. This approach makes it possible to minimize impacts to the source in pollution prevention. It is widely preferable to curative approach, currently majority in the industrial crops, led mostly by a report of pollution. The "product" is to reduce the environmental impacts of a given product, taking into account all or part of its life cycle. Currently, there are emerging tools, known as eco-design. They are intended to establish an environmental profile of the product to improve its environmental performance. They require a quantity sufficient information on the product for each phase of its life cycle: raw material extraction, manufacturing, distribution, usage, end of life (recycling or incineration or deposit) and all stages of transport. The assessment results indicate the sensitive points of the product studied, points on which the developer must act.

Keywords: eco design, impact, life cycle analysis (LCA), sustainability

Procedia PDF Downloads 407
2764 Determination of the Needs for Development of Infertility Psycho-Educational Program and the Design of a Website about Infertility for University Students

Authors: Bahar Baran, Şirin Nur Kaptan, D.Yelda Kağnıcı, Erol Esen, Barışcan Öztürk, Ender Siyez, Diğdem M Siyez

Abstract:

It is known that some factors associated with infertility have preventable characteristics and that young people's knowledge levels in this regard are inadequate, but very few studies focus on effective prevention studies on infertility. Psycho-educational programs have an important place for infertility prevention efforts. Nowadays, considering the households' utilization rates from technology and the Internet, it seems that young people have applied to websites as a primary source of information related to a health problem they have encountered. However, one of the prerequisites for the effectiveness of websites or face-to-face psycho-education programs is to consider the needs of participants. In particular, it is expected that these programs will be appropriate to the cultural infrastructure and the diversity of beliefs and values in society. The aim of this research is to determine what university students want to learn about infertility and fertility and examine their views on the structure of the website. The sample of the research consisted of 9693 university students who study in 21 public higher education programs in Turkey. 51.6 % (n = 5002) were female and 48.4% (n = 4691) were male. The Needs Analysis Questionnaire developed by the researchers was used as data collection tool in the research. In the analysis of the data, descriptive analysis was conducted in SPSS software. According to the findings, among the topics that university students wanted to study about infertility and fertility, the first topics were 'misconceptions about infertility' (94.9 %), 'misconceptions about sexual behaviors' (94.6 %), 'factors affecting infertility' (92.8 %), 'sexual health and reproductive health' (92.5 %), 'sexually transmitted diseases' (92.7 %), 'sexuality and society' (90.9 %), 'healthy life (help centers)' (90.4 %). In addition, the questions about how the content of the website should be designed for university students were analyzed descriptively. According to the results, 91.5 % (n = 8871) of the university students proposed to use frequently asked questions and their answers, 89.2 % (n = 8648) stated that expert video should be included, 82.6 % (n = 8008) requested animations and simulations, 76.1 % (n = 7380) proposed different content according to sex and 66 % (n = 6460) proposed different designs according to sex. The results of the research indicated that the findings are similar to the contents of the program carried out in other countries in terms of the topics to be studied. It is suggested to take into account the opinions of the participants during the design of website.

Keywords: infertility, prevention, psycho-education, web based education

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2763 Epigenetic Modifying Potential of Dietary Spices: Link to Cure Complex Diseases

Authors: Jeena Gupta

Abstract:

In the today’s world of pharmaceutical products, one should not forget the healing properties of inexpensive food materials especially spices. They are known to possess hidden pharmaceutical ingredients, imparting them the qualities of being anti-microbial, anti-oxidant, anti-inflammatory and anti-carcinogenic. Further aberrant epigenetic regulatory mechanisms like DNA methylation, histone modifications or altered microRNA expression patterns, which regulates gene expression without changing DNA sequence, contribute significantly in the development of various diseases. Changing lifestyles and diets exert their effect by influencing these epigenetic mechanisms which are thus the target of dietary phytochemicals. Bioactive components of plants have been in use since ages but their potential to reverse epigenetic alterations and prevention against diseases is yet to be explored. Spices being rich repositories of many bioactive constituents are responsible for providing them unique aroma and taste. Some spices like curcuma and garlic have been well evaluated for their epigenetic regulatory potential, but for others, it is largely unknown. We have evaluated the biological activity of phyto-active components of Fennel, Cardamom and Fenugreek by in silico molecular modeling, in vitro and in vivo studies. Ligand-based similarity studies were conducted to identify structurally similar compounds to understand their biological phenomenon. The database searching has been done by using Fenchone from fennel, Sabinene from cardamom and protodioscin from fenugreek as a query molecule in the different small molecule databases. Moreover, the results of the database searching exhibited that these compounds are having potential binding with the different targets found in the Protein Data Bank. Further in addition to being epigenetic modifiers, in vitro study had demonstrated the antimicrobial, antifungal, antioxidant and cytotoxicity protective effects of Fenchone, Sabinene and Protodioscin. To best of our knowledge, such type of studies facilitate the target fishing as well as making the roadmap in drug design and discovery process for identification of novel therapeutics.

Keywords: epigenetics, spices, phytochemicals, fenchone

Procedia PDF Downloads 141
2762 Frequency of Polymorphism of Mrp1/Abcc1 And Mrp2/Abcc2 in Healthy Volunteers of the Center Savannah (Colombia)

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

Abstract:

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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2761 Sex Work Practice and Health Seeking Behavior among Hiv Positive Female Sex Workers in Rural Karnataka, India

Authors: Rajeshwari Biradar

Abstract:

Background: The anecdotal evidences indicate that utilization of HIV services especially in Government facilities is affected by stigma and discrimination among HIV positive female sex workers (FSWs) in Karnataka. To our knowledge, there is no quantitative study on this issue. In this study an attempt is made to examine these aspects among positive FSWs exposed to prevention programs. Methods: This is a cross‐ sectional quantitative survey of HIV positive FSWs in the 3 districts of northern Karnataka using a structured questionnaire. The list of HIV Positive FSWs was organized by stratification, and 607 positive FSWs were selected using a systematic random selection. The data were analyzed using both bivariate and multivariate statistical techniques. Results: Half of the sex workers (52%) are traditional (devadasi, dedicated to the temple), 22% are widowed and the mean age is 33 years. The FSWs practice sex work on an average 13 days a month with 2.3 clients per day and was in sex work for about 13 years. Almost all of them (97%) used condom with the clients they had on the last day of sex work. About 74% were ever registered in the ART center and 47% of them reported being ever on ART, of which 6% dropped out. Multivariate results support the hypothesis that the interventions addressing stigma and discrimination enabled accessing health services in the government facilities (AOR=1.37; p=0.17). Conclusions: Based on the results of the study, programs addressing stigma, discrimination and positive prevention can be implemented in places where government health services are not utilized by HIV positive FSWs. However, the study may be limited by the fact that majority of the FSWs entered into sex work through the traditional devadasi system, which may not be the case in other parts of India.

Keywords: sex work, HIV/AIDS, female sex workers, health

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2760 In vitro Establishment and Characterization of Oral Squamous Cell Carcinoma Derived Cancer Stem-Like Cells

Authors: Varsha Salian, Shama Rao, N. Narendra, B. Mohana Kumar

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Evolving evidence proposes the existence of a highly tumorigenic subpopulation of undifferentiated, self-renewing cancer stem cells, responsible for exhibiting resistance to conventional anti-cancer therapy, recurrence, metastasis and heterogeneous tumor formation. Importantly, the mechanisms exploited by cancer stem cells to resist chemotherapy are very less understood. Oral squamous cell carcinoma (OSCC) is one of the most regularly diagnosed cancer types in India and is associated commonly with alcohol and tobacco use. Therefore, the isolation and in vitro characterization of cancer stem-like cells from patients with OSCC is a critical step to advance the understanding of the chemoresistance processes and for designing therapeutic strategies. With this, the present study aimed to establish and characterize cancer stem-like cells in vitro from OSCC. The primary cultures of cancer stem-like cell lines were established from the tissue biopsies of patients with clinical evidence of an ulceroproliferative lesion and histopathological confirmation of OSCC. The viability of cells assessed by trypan blue exclusion assay showed more than 95% at passage 1 (P1), P2 and P3. Replication rate was performed by plating cells in 12-well plate and counting them at various time points of culture. Cells had a more marked proliferative activity and the average doubling time was less than 20 hrs. After being cultured for 10 to 14 days, cancer stem-like cells gradually aggregated and formed sphere-like bodies. More spheroid bodies were observed when cultured in DMEM/F-12 under low serum conditions. Interestingly, cells with higher proliferative activity had a tendency to form more sphere-like bodies. Expression of specific markers, including membrane proteins or cell enzymes, such as CD24, CD29, CD44, CD133, and aldehyde dehydrogenase 1 (ALDH1) is being explored for further characterization of cancer stem-like cells. To summarize the findings, the establishment of OSCC derived cancer stem-like cells may provide scope for better understanding the cause for recurrence and metastasis in oral epithelial malignancies. Particularly, identification and characterization studies on cancer stem-like cells in Indian population seem to be lacking thus provoking the need for such studies in a population where alcohol consumption and tobacco chewing are major risk habits.

Keywords: cancer stem-like cells, characterization, in vitro, oral squamous cell carcinoma

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2759 The Effects of Metformin And PCL-sorafenib Nanoparticles Co-treatment on MCF-7 Cell Culture Model of Breast Cancer

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

Abstract:

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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2758 Discovery of New Inhibitors for Colorectal Cancer Treatment

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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