Search results for: population genetic
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 6941

Search results for: population genetic

5261 Population Pharmacokinetics of Levofloxacin and Moxifloxacin, and the Probability of Target Attainment in Ethiopian Patients with Multi-Drug Resistant Tuberculosis

Authors: Temesgen Sidamo, Prakruti S. Rao, Eleni Akllilu, Workineh Shibeshi, Yumi Park, Yong-Soon Cho, Jae-Gook Shin, Scott K. Heysell, Stellah G. Mpagama, Ephrem Engidawork

Abstract:

The fluoroquinolones (FQs) are used off-label for the treatment of multidrug-resistant tuberculosis (MDR-TB), and for evaluation in shortening the duration of drug-susceptible TB in recently prioritized regimens. Within the class, levofloxacin (LFX) and moxifloxacin (MXF) play a substantial role in ensuring success in treatment outcomes. However, sub-therapeutic plasma concentrations of either LFX or MXF may drive unfavorable treatment outcomes. To the best of our knowledge, the pharmacokinetics of LFX and MXF in Ethiopian patients with MDR-TB have not yet been investigated. Therefore, the aim of this study was to develop a population pharmacokinetic (PopPK) model of levofloxacin (LFX) and moxifloxacin (MXF) and assess the percent probability of target attainment (PTA) as defined by the ratio of the area under the plasma concentration-time curve over 24-h (AUC0-24) and the in vitro minimum inhibitory concentration (MIC) (AUC0-24/MIC) in Ethiopian MDR-TB patients. Steady-state plasma was collected from 39 MDR-TB patients enrolled in the programmatic treatment course and the drug concentrations were determined using optimized liquid chromatography-tandem mass spectrometry. In addition, the in vitro MIC of the patients' pretreatment clinical isolates was determined. PopPK and simulations were run at various doses, and PK parameters were estimated. The effect of covariates on the PK parameters and the PTA for maximum mycobacterial kill and resistance prevention was also investigated. LFX and MXF both fit in a one-compartment model with adjustments. The apparent volume of distribution (V) and clearance (CL) of LFX were influenced by serum creatinine (Scr), whereas the absorption constant (Ka) and V of MXF were influenced by Scr and BMI, respectively. The PTA for LFX maximal mycobacterial kill at the critical MIC of 0.5 mg/L was 29%, 62%, and 95% with the simulated 750 mg, 1000 mg, and 1500 mg doses, respectively, whereas the PTA for resistance prevention at 1500 mg was only 4.8%, with none of the lower doses achieving this target. At the critical MIC of 0.25 mg/L, there was no difference in the PTA (94.4%) for maximum bacterial kill among the simulated doses of MXF (600 mg, 800 mg, and 1000 mg), but the PTA for resistance prevention improved proportionately with dose. Standard LFX and MXF doses may not provide adequate drug exposure. LFX PopPK is more predictable for maximum mycobacterial kill, whereas MXF's resistance prevention target increases with dose. Scr and BMI are likely to be important covariates in dose optimization or therapeutic drug monitoring (TDM) studies in Ethiopian patients.

Keywords: population PK, PTA, moxifloxacin, levofloxacin, MDR-TB patients, ethiopia

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5260 Educators’ Perceived Capacity to Create Inclusive Learning Environments: Exploring Individual Competencies and District Policy

Authors: Thuy Phan, Stephanie Luallin

Abstract:

Inclusive education policies have demonstrated benefits for students with and without disabilities in the US. There are several laws that relate to inclusive education, such as 'No Child Left Behind', 'The Individuals with Disabilities Education Act'. However, the application of these inclusive education laws and policies vary per state and school district. Classroom teachers in an inclusive classroom often experience confusion as to how to apply these policies in order to create appropriate inclusive learning environments that meet the abilities and needs of their diverse student population. The study aims to investigate teachers’ perspective of their capacities to create an appropriate learning environment for their diverse student population including students with disabilities. Qualitative method is implemented in this study, using open-end interview questions to investigate teachers’ perspective of their capacities to create an appropriate inclusive learning environment for all students based on current inclusive education laws and district policies in the state of Colorado, USA. These findings may indicate a lack of confidence in teachers’ capacity to create appropriate inclusive learning environments based on laws and district policies; including challenges that classroom teachers may experience in creating inclusive learning environments. The purpose of this study is to examine the adequate preparation of classroom teachers in creating inclusive classrooms with the intent of determining implications for developing policies in inclusive education.

Keywords: educator’s capacity, inclusive education, inclusive learning environment, policy

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5259 An Immersive Serious Game for Firefighting and Evacuation Training in Healthcare Facilities

Authors: Anass Rahouti, Guillaume Salze, Ruggiero Lovreglio, Sélim Datoussaïd

Abstract:

In healthcare facilities, training the staff for firefighting and evacuation in real buildings is very challenging due to the presence of a vulnerable population in such an environment. In a standard environment, traditional approaches, such as fire drills, are often used to train the occupants and provide them with information about fire safety procedures. However, those traditional approaches may be inappropriate for a vulnerable population and can be inefficient from an educational viewpoint as it is impossible to expose the occupants to scenarios similar to a real emergency. Immersive serious games could be used as an alternative to traditional approaches to overcome their limitations. Serious games are already being used in different safety domains such as fires, earthquakes and terror attacks for several building types (e.g., office buildings, train stations, tunnels, etc.). In this study, we developed an immersive serious game to improve the fire safety skills of staff in healthcare facilities. An accurate representation of the healthcare environment was built in Unity3D by including visual and audio stimuli inspired from those employed in commercial action games. The serious game is organised in three levels. In each of them, the trainee is presented with a specific fire emergency and s/he can perform protective actions (e.g., firefighting, helping non-ambulant occupants, etc.) or s/he can ignore the opportunity for action and continue the evacuation. In this paper, we describe all the steps required to develop such a prototype, as well as the key questions that need to be answered, to develop a serious game for firefighting and evacuation in healthcare facilities.

Keywords: fire safety, healthcare, serious game, training

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5258 Examining the Predictors of Non-Urgent Emergency Department Visits: A Population Based Study

Authors: Maher El-Masri, Jamie Crawley, Judy Bornais, Abeer Omar

Abstract:

Background: Misuse of Emergency Department (ED) for non-urgent healthcare results in unnecessary crowdedness that can result in long ED waits and delays in treatment, diversion of ambulances to other hospitals, poor health outcomes for patients, and increased risk of death Objectives: The main purpose of this study was to explore the independent predictors of non-urgent ED visits in Erie St. Clair LHIN. Secondary purposes of the study include comparison of the rates of non-urgent ED visits between urban and rural hospitals Design: A secondary analysis of archived population-based data on 597,373 ED visits in southwestern Ontario Results The results suggest that older (OR = .992; 95% CI .992 – .993) and female patients (OR = .940; 95% CI .929 - .950) were less likely to visit ED for non-urgent causes. Non-urgent ED visits during the winter, spring, and fall were 13%, 5.8%, and 7.5%, respectively, lesser than they were during the summer time. The data further suggest that non-urgent visits were 19.6% and 21.3% less likely to occur in evening and overnight shifts compared to the day shift. Non-urgent visits were 2.76 times more likely to present to small community hospitals than large community hospitals. Health care providers were 1.92 times more likely to refer patients with non-urgent health problem to the ED than the decision taken by patients, family member or caretakers. Conclusion: In conclusion, our study highlights a number of important factors that are associated with inappropriate use of ED visits for non-urgent health problems. Knowledge of these factors could be used to address the issue of unnecessary ED crowdedness.

Keywords: emergency department, non-urgent visits, predictors, logistic regression

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5257 Pattern Discovery from Student Feedback: Identifying Factors to Improve Student Emotions in Learning

Authors: Angelina A. Tzacheva, Jaishree Ranganathan

Abstract:

Interest in (STEM) Science Technology Engineering Mathematics education especially Computer Science education has seen a drastic increase across the country. This fuels effort towards recruiting and admitting a diverse population of students. Thus the changing conditions in terms of the student population, diversity and the expected teaching and learning outcomes give the platform for use of Innovative Teaching models and technologies. It is necessary that these methods adapted should also concentrate on raising quality of such innovations and have positive impact on student learning. Light-Weight Team is an Active Learning Pedagogy, which is considered to be low-stake activity and has very little or no direct impact on student grades. Emotion plays a major role in student’s motivation to learning. In this work we use the student feedback data with emotion classification using surveys at a public research institution in the United States. We use Actionable Pattern Discovery method for this purpose. Actionable patterns are patterns that provide suggestions in the form of rules to help the user achieve better outcomes. The proposed method provides meaningful insight in terms of changes that can be incorporated in the Light-Weight team activities, resources utilized in the course. The results suggest how to enhance student emotions to a more positive state, in particular focuses on the emotions ‘Trust’ and ‘Joy’.

Keywords: actionable pattern discovery, education, emotion, data mining

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5256 Comparing Media-Based Strategies of Identity Formation in Chicanos and Cuban-Americans

Authors: Kwang Yeon Kim

Abstract:

This paper will explore the directly proportional relationship between the influence of Hispanophone media in U.S. markets and Hispanic population growth. Though this growth has origins across south and central America, in U.S. media markets Mexican and Cuban immigrants, have traditionally been considered the most influential. Having endured significant historical discrimination, disparagement, and ethnic framing from conventional Anglophone media, such groups have sought to form their own identities as media consuming and producing Americans of Latin American origin. Although immigrants to the U.S. have traditionally faced obstacles in access to education, children of Mexican-Americans (Chicanos) and Cuban-Americans have made significant progress in overcoming these obstacles, partly explaining their media dominance. This is particularly true in the case of Cuban-Americans, for whom such media presence is not predicted by share of population. By conducting comparative studies of Chicano media and Cuban-Americans media, common ground was found in strategies of reliance on media-driven identity formation. In contrast to the mainstream media portrayal of Latino/as with limiting, negative stereotypes, Spanish-language media’s goal is to form the identity of being Latino for those living in the United States. Providing both news from countries of origin and local news within the United States, Chicano and Cuban-American media performs rituals of recollection while rooting such populations in more proximate media paradigms.

Keywords: Chicano identity, Cuban-Americans, Hispanophone media, Latino/a community

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5255 The Lived Experience of Pregnant Saudi Women Carrying a Fetus with Structural Abnormalities

Authors: Nasreen Abdulmannan

Abstract:

Fetal abnormalities are categorized as a structural abnormality, non-structural abnormality, or a combination of both. Fetal structural abnormalities (FSA) include, but are not limited, to Down syndrome, congenital diaphragmatic hernia, and cleft lip and palate. These abnormalities can be detected in the first weeks of pregnancy, which is almost around 9 - 20 weeks gestational. Etiological factors for FSA are unknown; however, transmitted genetic risk can be one of these factors. Consanguineous marriage often referred to as inbreeding, represents a significant risk factor for FSA due to the increased likelihood of deleterious genetic traits shared by both biological parents. In a country such as the Kingdom of Saudi Arabia (KSA), consanguineous marriage is high, which creates a significant risk of children being born with congenital abnormalities. Historically, the practice of consanguinity occurred commonly among European royalty. For example, Great Britain’s Queen Victoria married her German first cousin, Prince Albert of Coburg. Although a distant blood relationship, the United Kingdom’s Queen Elizabeth II married her cousin, Prince Philip of Greece and Denmark—both of them direct descendants of Queen Victoria. In Middle Eastern countries, a high incidence of consanguineous unions still exists, including in the KSA. Previous studies indicated that a significant gap exists in understanding the lived experiences of Saudi women dealing with an FSA-complicated pregnancy. Eleven participants were interviewed using a semi-structured interview format for this qualitative phenomenological study investigating the lived experiences of pregnant Saudi women carrying a child with FSA. This study explored the gaps in current literature regarding the lived experiences of pregnant Saudi women whose pregnancies were complicated by FSA. In addition, the researcher acquired knowledge about the available support and resources as well as the Saudi cultural perspective on FSA. This research explored the lived experiences of pregnant Saudi women utilizing Giorgi’s (2009) approach to data collection and data management. Findings for this study cover five major themes: (1) initial maternal reaction to the FSA diagnosis per ultrasound screening; (2) strengthening of the maternal relationship with God; (3) maternal concern for their child’s future; (4) feeling supported by their loved ones; and (5) lack of healthcare provider support and guidance. Future research in the KSA is needed to explore the network support for these mothers. This study recommended further clinical nursing research, nursing education, clinical practice, and healthcare policy/procedures to provide opportunities for improvement in nursing care and increase awareness in KSA society.

Keywords: fetal structural abnormalities, psychological distress, health provider, health care

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5254 Analytical Study of Data Mining Techniques for Software Quality Assurance

Authors: Mariam Bibi, Rubab Mehboob, Mehreen Sirshar

Abstract:

Satisfying the customer requirements is the ultimate goal of producing or developing any product. The quality of the product is decided on the bases of the level of customer satisfaction. There are different techniques which have been reported during the survey which enhance the quality of the product through software defect prediction and by locating the missing software requirements. Some mining techniques were proposed to assess the individual performance indicators in collaborative environment to reduce errors at individual level. The basic intention is to produce a product with zero or few defects thereby producing a best product quality wise. In the analysis of survey the techniques like Genetic algorithm, artificial neural network, classification and clustering techniques and decision tree are studied. After analysis it has been discovered that these techniques contributed much to the improvement and enhancement of the quality of the product.

Keywords: data mining, defect prediction, missing requirements, software quality

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5253 The Influence of Carbamazepine on the Activity of CYP3A4 in Patients with Alcoholism

Authors: Mikhail S. Zastrozhin, Valery V. Smirnov, Dmitry A. Sychev, Ludmila M. Savchenko, Evgeny A. Bryun, Mark O. Nechaev

Abstract:

Cytochrome P-450 isoenzyme 3A4 takes part in the biotransformation of medical drugs. The activity of CYP isoenzymes depends on genetic (polymorphisms of genes which encoded it) and phenotypic factors (a kind of food, a concomitant drug therapy). The aim of the study was to evaluate a carbamazepine effect on the CYP3A4 activity in patients with alcohol addiction. The study included 25 men with alcohol dependence, who received haloperidol during the exacerbation of the addiction. CYP3A4 activity was assessed by urinary 6-beta-hydroxycortisol/cortisol ratios measured by high performance liquid chromatography with mass spectrometry. The study modeled a graph and an equation of the logarithmic regression, that reflects the dependence of CYP3A4 activity on a dose of carbamazepine: y = 5,5 * 9,1 * 10-5 * x2. The study statistically significant demonstrates the effect of carbamazepine on CYP2D6 isozyme activity in patients with alcohol addiction.

Keywords: CYP3A4, biotransformation, carbamazepine, alcohol abuse

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5252 Integrated Location-Allocation Planning in Multi Product Multi Echelon Single Period Closed Loop Supply Chain Network Design

Authors: Santhosh Srinivasan, Vipul Garhiya, Shahul Hamid Khan

Abstract:

Environmental performance along with social performance is becoming vital factors for industries to achieve global standards. With a good environmental policy global industries are differentiating them from their competitors. This paper concentrates on multi stage, multi product and multi period manufacturing network. Single objective mathematical models for a total cost for the entire forward supply chain and reverse chain are considered. Here five different problems are considered by varying the number of facilities for illustration. M-MOGA, Shuffle Frog Leaping algorithm (SFLA) and CPLEX are used for finding the optimal solution for the mathematical model.

Keywords: closed loop supply chain, genetic algorithm, random search, multi period, green supply chain

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5251 Major Histocompatibility Complex (MHC) Polymorphism and Disease Resistance

Authors: Oya Bulut, Oguzhan Avci, Zafer Bulut, Atilla Simsek

Abstract:

Livestock breeders have focused on the improvement of production traits with little or no attention for improvement of disease resistance traits. In order to determine the association between the genetic structure of the individual gene loci with possibility of the occurrence and the development of diseases, MHC (major histocompatibility complex) are frequently used. Because of their importance in the immune system, MHC locus is considered as candidate genes for resistance/susceptibility against to different diseases. Major histocompatibility complex (MHC) molecules play a critical role in both innate and adaptive immunity and have been considered candidate molecular markers of an association between polymorphisms and resistance/susceptibility to diseases. The purpose of this study is to give some information about MHC genes become an important area of study in recent years in terms of animal husbandry and determine the relation between MHC genes and resistance/susceptibility to disease.

Keywords: MHC, polymorphism, disease, resistance

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5250 Design and in Slico Study of the Truncated Spike-M-N SARS-CoV-2 as a Novel Effective Vaccine Candidate

Authors: Aghasadeghi MR., Bahramali G., Sadat SM., Sadeghi SA., Yousefi M., Khodaei K., Ghorbani M., Sadat Larijani M.

Abstract:

Background:The emerging COVID-19 pandemic is a serious concernfor the public health worldwide. Despite the many mutations in the virus genome, it is important to find an effective vaccine against viral mutations. Therefore, in current study, we aimed at immunoinformatic evaluation of the virus proteins immunogenicity to design a preventive vaccine candidate, which could elicit humoral and cellular immune responses as well. Methods:Three antigenic regions are included;Spike, Membrane, and Nucleocapsid amino acid sequences were obtained, and possible fusion proteins were assessed andcompared by immunogenicity, structural features, and population coverage. The best fusion protein was also evaluated for MHC-I and MHC-II T-cell epitopes and the linear and conformational B-cell epitopes. Results: Among the four predicted models, the truncated Spike protein in fusion with M and N proteins is composed of 24 highly immunogenic human MHC class I and 29 MHC class II, along with 14 B-cell linear and 61 discontinues epitopes. Also, the selected protein has high antigenicity and acceptable population coverage of 82.95% in Iran and 92.51% in Europe. Conclusion: The data indicate that the truncated Spike-M-N SARS-CoV-2form which could be potential targets of neutralizing antibodies. The protein also has the ability to stimulate humoral and cellular immunity. The in silico study provided the fusion protein as a potential preventive vaccine candidate for further in vivo evaluation.

Keywords: SARS-CoV-2, immunoinformatic, protein, vaccine

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5249 Variability in Contraception Choices and Abortion Rates among Female Garment Factory Workers in Urban and Rural Cambodia

Authors: Olalekan Olaluwoye, Joanne Williams, Elizabeth Hoban

Abstract:

Background: Modern contraceptives are effective in preventing unwanted pregnancies and therefore the potential to reduce abortion rates. There is a need for information about how rates of contraceptive use and abortion vary across Cambodia and the relationship between the prevalence of modern contraception use and abortion rates. This study compares the use of contraception and abortion among female garment factory workers in rural and urban areas of Cambodia. Method: Cross-sectional surveys were conducted with 1701 women working in eleven garment factories in rural and urban areas of Cambodia. Sexual and reproductive health data were collected using Audio-Assisted Survey Interviews and analysed using STATA 14 software. Findings: Over 70% of the respondents were less than 30 years of age across both rural and urban settings and over 50% have only primary education, thus the study population was largely young women with limited education. A significantly higher proportion of the rural women earned over $200 in the previous month compared with their urban counterparts. The majority of the urban women (51.5%) were married, while single women (46.9%) made up the largest group working in the rural factories. A significantly larger proportion of women in the rural areas (83.9%) were sexually active compared to the urban women (50.9%). More women from the rural areas (41.4%) had been pregnant at some time compared with the urban population (37.7%). The use of any contraceptive method among sexually active women was significantly higher in the rural areas (80.1%) compared to the urban areas (65.7%) with p-value=0.000. However, among those women who used contraception, the prevalence of modern contraception use was slightly higher in the urban population (68.8% urban, 63.4% rural, p-value=0.1). For women who had a history of pregnancy the abortion prevalence was higher among rural women (43.8%) compared to their urban counterparts (37.7%). Regression analysis showed that after adjustment for the demographic variables (age, relationship status, income, education) only age and relationship status had a significant influence on the use of modern contraception.Single females who were sexually active and older women, who had potentially completed their families, were more likely to choose modern contraception. Conclusion: Although overall the use of contraception was higher among rural women, the use of modern contraception was higher among urban women.This finding may partly explain the higher rates of abortion among women in the rural areas as traditional contraception methods have higher failure rates and are more likely to result in an unplanned pregnancy.Despite the regional variation, the high rates of abortion across the country suggest there is a need for improve education on family planning among female garment factory workers in Cambodia.

Keywords: abortion, Cambodia, contraception, garment factory

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5248 Cultural Competence and Healthcare Challenges of Migrants in South Wales United Kingdom

Authors: Qirat Naz, Abasiokpon Udoakah

Abstract:

In developed countries, global migration is diversifying. The minority ethnic population, including refugees and asylum seekers who, fled their home countries due to war, terrorism, oppression, or natural disasters, and returning home is dangerous for them. They need sanctuary and peaceful environment in host countries. They begin the process of acculturation, in which a person adopts the social mores and behavioral patterns of the dominant culture, yet they still have unique multicultural needs that the dominant society fails to address. The aim of this research is to provide a holistic understanding of the living experiences of a minority population, particularly migrants, including asylum seekers and refugees, in the health and social care system of South Wales. The purpose of this study is to investigate three research objectives: the multicultural health care needs of minorities, as well as the barriers to seeking health and social care facilities. There are Welsh policies for promoting cultural competence in the health and social care sectors; this research will explore the implications and impact of these policies on the target population. This research study will be conducted using qualitative research methods, tools, and techniques. This research is an inductive approach to coming up with a grounded theory. The sample will be divided into two groups: migrants and professionals providing any kind of services to migrants; each group will contain 30 participants. Interpretive phenomenological analysis would be utilized during the process of coding and developing the main themes of this research. The positionality of the researcher would be minimized by unloaded and open-ended questions, researcher’s work experience in research, continuous evaluation of her positionality, daily base reflection of fieldwork and seeking the help of male and female gatekeepers. The research findings would be based on emic perspective, and by documenting the emic perspective of minorities, this research will contribute to the knowledge of appropriate channels, including organizations, academics, and policymakers, to discover possible solutions and coping mechanisms to deal with the challenges and meet the multicultural demands of minorities. This research will provide a more in-depth understanding of minorities and will help to promote the diversity of health and social care in South Wales.

Keywords: migration, migrants, cultural competence, cultural barriers, healthcare challenges

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5247 The Relationship between the Epithermal Mineralization, Thermalism, and Basement Faults in the Region of Guelma: NE of Algeria

Authors: B. Merdas

Abstract:

The Guelma region constitutes a vast geothermal field whose local geothermal gradient is very high. Indeed, various thermal and thermo sources emerging in the region, including some at relatively high temperatures. In the mio Pliocene Hammam N'bails, basin emerges a hot spring that leaves develop a thick series of thermal travertine linked to it. Near the thermal emergences has settled a very special mineralization antimony and zinc and lead. The results of analyses of the thermal waters of the source of Hammam N'bails and the associated travertine, show abnormal values in Pb, Sb, Zn, As, and other metals, demonstrating the genetic link between those waters and mineralization. Hammam N'bails mineralizations by their mineral assembling represented and their association with the hot springs, are very similar to epithermal deposits with precious metals (gold and silver) like Senator mine in Turkey or ‘Carlin-type’ in Nevada (USA).

Keywords: hot springs, mineralization; basement faults, Guelma, NE Algeria

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5246 Evaluation of the Pain of Patients with Chronic Renal Disease in Hemodialysis

Authors: Fabiana Souza Orlandi, Izabel Cristina Chavez Gomes, Barbara Isabela De Paula Morais, Ana Carolina Ottaviani

Abstract:

Chronic Kidney Disease (CKD) is considered a public health problem. Patients who present CKD in their more advanced stages usually present several biopsychosocial changes, which may include pain. Pain can be considered subjective and personal, and its perception is characterized as a multidimensional experience. The objective of this study was to evaluate the level and descriptors of pain of adults and elderly patients with chronic kidney disease, through the Multidimensional Pain Evaluation Scale (EMADOR). This is a descriptive cross-sectional study with a quantitative approach. The sample consisted of 100 subjects with CKD in hemodialysis treatment at a Renal Replacement Therapy Service in the interior of the state of São Paulo. Data were collected through an individual interview, using a Sociodemographic Characterization and Multidimensional Pain Evaluation Scale (EMADOR). All ethical precepts were respected. The majority of the respondents were men (61.0%), white (56.0%) and with a high school education (34.0%). Regarding the pain of the individuals, 89 patients reported pain, with Chronic Pain predominating (50.0%, n = 50), followed by Acute Pain (39.0%, n = 39). Of the subjects who presented acute pain most of the 89.0% described the pain felt as unbearable, and of those who presented chronic pain, 35.0% described the pain felt as painful, unbearable and uncomfortable. It was concluded that there was a significant presence of pain, being the chronic pain dominant in the studied population. Faced with such factors, the present study motivates researches in this population, in order to establish interventions with the objective of improving the quality of life of these individuals.

Keywords: pain, chronic kidney disease, dialysis, evaluation

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5245 Clinical Impact of Ultra-Deep Versus Sanger Sequencing Detection of Minority Mutations on the HIV-1 Drug Resistance Genotype Interpretations after Virological Failure

Authors: S. Mohamed, D. Gonzalez, C. Sayada, P. Halfon

Abstract:

Drug resistance mutations are routinely detected using standard Sanger sequencing, which does not detect minor variants with a frequency below 20%. The impact of detecting minor variants generated by ultra-deep sequencing (UDS) on HIV drug-resistance (DR) interpretations has not yet been studied. Fifty HIV-1 patients who experienced virological failure were included in this retrospective study. The HIV-1 UDS protocol allowed the detection and quantification of HIV-1 protease and reverse transcriptase variants related to genotypes A, B, C, E, F, and G. DeepChek®-HIV simplified DR interpretation software was used to compare Sanger sequencing and UDS. The total time required for the UDS protocol was found to be approximately three times longer than Sanger sequencing with equivalent reagent costs. UDS detected all of the mutations found by population sequencing and identified additional resistance variants in all patients. An analysis of DR revealed a total of 643 and 224 clinically relevant mutations by UDS and Sanger sequencing, respectively. Three resistance mutations with > 20% prevalence were detected solely by UDS: A98S (23%), E138A (21%) and V179I (25%). A significant difference in the DR interpretations for 19 antiretroviral drugs was observed between the UDS and Sanger sequencing methods. Y181C and T215Y were the most frequent mutations associated with interpretation differences. A combination of UDS and DeepChek® software for the interpretation of DR results would help clinicians provide suitable treatments. A cut-off of 1% allowed a better characterisation of the viral population by identifying additional resistance mutations and improving the DR interpretation.

Keywords: HIV-1, ultra-deep sequencing, Sanger sequencing, drug resistance

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5244 Evaluation of Anti-Cancer Activities of Formononetin in Lung Cancer by in vitro Methods

Authors: Vishnu Varthan Vaithiyalingam Jagannathan, Lakshmi Karunanidhi Santhanalakshmi, Srividya Ammayappan Rajam

Abstract:

Formononetin is the O-Methoxy Flavonol that has many pharmacological activities, which belongs to the flavonoid family. In the current study, activity of this molecule was evaluated in lung cancer cell lines. In general, flavonoids possess certain anticancer mechanism. Being a flavonoid subfamily, this molecule was subjected to evaluate cytotoxicity assay by MTT ((3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide)) stain, mode of cell death assay stained by acridine orange and ethidium bromide and Evaluation of Apoptosis pathway (extrinsic or intrinsic) by Caspase 3/7 stain and Rhodamine-123 stain. From the results, we could able to confirm that the investigatory molecule formononetin has anticancer activity and in future, the study will propose to evaluate the formononetin action against genetic changes occurs during lung cancer progression.

Keywords: Caspase 3/7, formononetin, lung cancer, Rhodamine-123

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5243 Yoga as a Tool for Public Health

Authors: Divya Kanchibhotla

Abstract:

Of all the major health threats to emerge, none has challenged the very foundation of public health so profoundly as the rise of non-communicable diseases (NCD). Encouraging a holistic health approach encompasses the community’s well-being. Competent public health grounded with holistic health approach can lay a better foundation in the modern world. Yoga has been increasingly explored as an adjunct therapy to major disorders. This study explores the efficacy of Yoga as a tool for public health. A survey was administered to 5500 adults, and 300 teens were selected from 25 states of India. The study explored the differences in health, happiness, and sustainable living between Yoga-practitioners and Non-yoga practitioners. The study also explored the practice and habits of yoga practitioners (frequency, place, reasons to practice) and Health, Happiness, and Sustainable Living. The subjects were grouped based on age, education, experience in yoga (years of practice), and occupational background. The study population comprised of 54% males and 46% females. Majority of the respondents (59%) were from 18 to 30 years age group. The study indicated that 96.4% of the total respondents have heard of Yoga. However, only 46.8% of the total study population practice yoga (YP) and the rest 53.2% were non-practitioners (NP). From a perspective of how Yoga and health, 72.7% yoga practitioners asserted a peaceful and happy life, 71.9% yoga practitioners felt satisfaction in life, and 70.2 % yoga practitioners had satisfactory health. 61.9% of yoga practitioners report being vegetarian, not eating junk food, and not drinking alcohol than 38.1% Non-Practitioners population. 47% of yoga practitioners found themselves to be more sensitive to the environment compared to only 40% of non-practitioners. India has been witnessing an unprecedented rise in the NCDs, accounting for 61% deaths. The importance of yoga as an adjunct therapy for various disorders and diseases is gaining momentum across the globe. There are various studies on yoga that have indicated benefits of yoga as a unique holistic approach towards lifestyle and a consistent, complementary solution that could be adopted for long-term viability for a well being. The comprehensive study is the first of its kind that takes a holistic look at the prevalence of Yoga for public health in India. Our study is unique and stands out as it is detailed in its outlook with extensive coverage of almost the whole country (surveying 25 out of 29 states) and contemplates on the benefits to an individual at the grass-root level – physical, mental and social outlook. The insights from the study will enable the health care systems and grassroots organizations to make the holistic practice of Yoga accessible to spread sustainable living for a healthy community.

Keywords: non-communicable disease (NCD), sustainable development goal (SDG 3), public health, healthy living

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5242 Stature Prediction from Anthropometry of Extremities among Jordanians

Authors: Amal A. Mashali, Omar Eltaweel, Elerian Ekladious

Abstract:

Stature of an individual has an important role in identification, which is often required in medico-legal practice. The estimation of stature is an important step in the identification of dismembered remains or when only a part of a skeleton is only available as in major disasters or with mutilation. There is no published data on anthropological data among Jordanian population. The present study was designed in order to find out relationship of stature to some anthropometric measures among a sample of Jordanian population and to determine the most accurate and reliable one in predicting the stature of an individual. A cross sectional study was conducted on 336 adult healthy volunteers , free of bone diseases, nutritional diseases and abnormalities in the extremities after taking their consent. Students of Faculty of Medicine, Mutah University helped in collecting the data. The anthropometric measurements (anatomically defined) were stature, humerus length, hand length and breadth, foot length and breadth, foot index and knee height on both right and left sides of the body. The measurements were typical on both sides of the bodies of the studied samples. All the anthropologic data showed significant relation with age except the knee height. There was a significant difference between male and female measurements except for the foot index where F= 0.269. There was a significant positive correlation between the different measures and the stature of the individuals. Three equations were developed for estimation of stature. The most sensitive measure for prediction of a stature was found to be the humerus length.

Keywords: foot index, foot length, hand length, humerus length, stature

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5241 Pattern Of Polymorphism SLC22A1 Gene In Children With Diabetes Mellitus Type 2

Authors: Elly Usman, S. Dante, Diah Purnamasari

Abstract:

Type 2 diabetes mellitus ( T2DM ) is a syndrome characterized by a state of increased blood sugar levels due to chronic disorders of insulin secretion by pancreatic beta cells and insulin action or a combination of both. The organic cation transporter 1, encoded by the SLC22A1 gene, responsible for the uptake of the antihyperglycemic drug, metformin, in the hepatocyte. We assessed whether a genetic variation in the SLC22A1 gene was associated with the glucose - lowering effect of metformin. Method case study research design. Samples are children with type 2 diabetes mellitus who meet the inclusion criteria. The results proportions SLC22A1 gene polymorphisms in children with diabetes mellitus type 2 amounted to 52.04 % at position 400T/C, there is one heterozygous and one at position 595T/C Conclusion The presence of SLC22A1 gene polymorphisms in children with diabetes mellitus type 2.

Keywords: diabetes Mellitus type 2, metformin, organic cation transporter 1, pharmacogenomics

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5240 Dietary Factors Contributing to Osteoporosis among Postmenopausal Women in Riyadh Armed Forces Hospital

Authors: Rabab Makki

Abstract:

Bone mineral density and bone metabolism are affected by various factors such as genetic, endocrine, mechanical and nutritional. Our understanding of nutritional influences on bone health is limited because most studies have focused on calcium. This study investigated the dietary factors which are likely t contribute to Osteoporosis in Saudi post-menopausal women, and correlated it with BMD. This is a case controlled study involved 36 postmenopausal Saudi females selected from the Orthopedics and osteoporosis outpatient clinics, and 25 postmenopausal Saudi females as controls from the primary clinic of Military Hospital in Riyadh. The women were diagnosed as osteoporotic based on the BMD measurement at any site (left femur neck, right femur neck, left total hip or right total hip or spine). Both the controls and the Osteoporotics were over 50 years of age and BMI between 31-34 kg/m2 had 2nd degree obesity, and were not free from other problems such as diabetes, hypertension, etc. Subjects (osteoporotics and controls) were interviewed to called data on demographic characterstics, medical history, dietary intake anthropometry (height and weight) bone mineral density. Blood samples were collected from subjects (Osteoporotics and controls). Analysis of serum calcium, vitamin D, phosphate were done at the main laboratory at Military Hospital Riyadh, by the laboratory technician while BMD was determined at the department of Nuclear Medicine by an expert technician and results were interpreted by radiologist.Data on frequency of consumption of animal food (meat, eggs, poultry and fish) and diary foods (milk, yogurt, cheese) of osteoporotic was less than control. In spite of the low intake there was no association with BMD.In general, the vegetables and fruits were consumed less by the osteoporotics than control. The only fruit which had shown a significant positive correlation is banana with right and left hip BMD total probably due to high potassium and minerals content which likely to prevent bone resorption. Mataziz vegetables combination of wheat showed a significant positive correlation with the same site (total right and left hip). Both osteoporotics abd controls were consuming table sugar. (But the sweet intake showed a significant negative correlation with left neck femur BMD, suggesting sucrose increase urinary calcium loss. Both osteoporotic and controls were consuming Arabic coffee. A negative significant correlation between intake of Arabic coffee and BMD of right neck femur of osteoporosis patient was observed. It could be suggested that increased intake of fruits and vegetables, might promote bone density while high intake of coffee and sugars might affect bone density, no significant correlation was observed between BMD at any site and diary product. We can say the major risk factors are inadequate nutrition. Further studies are needed among Saudi population to confirm these results.

Keywords: osteoporosi, Saudia Arabia, Riyadh Armed Forces, postmenopausal women

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5239 Active Ageing a Way Forward to Healthy Ageing Among the Rural Elderly Women

Authors: Hannah Evangeline Sangeetha

Abstract:

Ageing is an inevitable change in the life span of an individual. India’s old age population has increased from 19 million in 1947 to 100 million in the 21st century. The United Nations World Population ageing reports that the grey population has immensely increased from 9.2% in 1990 to 11.7 % in 2013, and it’s expected to triple by the year 2050 growing from 737 million to over 2 billion persons 60 years of age and older. Ageing is a period of physical, mental and social decline which brings a host of challenges to the individual and the family. Hence it requires attention at the micro, mezzo and the macro levels of the society. The concepts of healthy and successful aging are being used to help people to change their negative attitude towards aging. This perspective is important to make people realize their potentialities to bring about a change in the minds of senior citizens as well as the society. The objective of this study was to understand the level of active ageing among the rural elderly women and its impact on the quality of life. 330 elderly women from 12 villages of Sriperumbudur associated with the Mobile medical care of Help age India were interviewed using census method. The study revealed the following findings; most respondents in this study were young old between the age group of 60 to 75 years. All the three major religious groups were represented, 85.5percent were Hindus. Majority of the respondents 73.3percent had no education. It was interesting to know that majority of the respondents were self reliant (83.94 percent) and 82.73 percent of them very independent and took care of them by themselves (activities of daily living) without any support from their families. 76.9 percent of the senior women worked based on their competencies, 75.5 percent of them were involved in plenty of activities everyday including their occupation and household chores, which enabled them to be physically active. The chi square values that there is a significant association between the overall active ageing score, religion &number of members in the family. The other demographic variables like age, occupation, income marital status, age at marriage, number of children in the family and Socio –Economic Status were not significantly associated with the overall active aging score. The p-value 0.032 showed Social network and being self-reliant are significantly associated. The study surprisingly shows that most women enjoyed freedom and Independence in their family which is a positive indicator of active ageing.

Keywords: active ageing, quality of life, independence, self reliance

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5238 DeepOmics: Deep Learning for Understanding Genome Functioning and the Underlying Genetic Causes of Disease

Authors: Vishnu Pratap Singh Kirar, Madhuri Saxena

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Advancement in sequence data generation technologies is churning out voluminous omics data and posing a massive challenge to annotate the biological functional features. With so much data available, the use of machine learning methods and tools to make novel inferences has become obvious. Machine learning methods have been successfully applied to a lot of disciplines, including computational biology and bioinformatics. Researchers in computational biology are interested to develop novel machine learning frameworks to classify the huge amounts of biological data. In this proposal, it plan to employ novel machine learning approaches to aid the understanding of how apparently innocuous mutations (in intergenic DNA and at synonymous sites) cause diseases. We are also interested in discovering novel functional sites in the genome and mutations in which can affect a phenotype of interest.

Keywords: genome wide association studies (GWAS), next generation sequencing (NGS), deep learning, omics

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5237 Expanding the World: Public and Global Health Experiences for Undergraduate Nursing Students

Authors: Kristen Erekson, Sarah Spendlove Caswell

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Nurse educators have the challenge of training future nurses that will provide compassionate care to an increasingly diverse population of patients in a culturally sensitive way. One approach to this challenge is an immersive public and global health experience as part of the nursing program curriculum. Undergraduate nursing students at our institution are required to participate in a Public and Global Health course. They participate in a didactic preparatory course followed by a 3-to-4-week program in one of the following locations: The Czech Republic, Ecuador, Finland/Poland, Ghana, India, Spain, Taiwan, Tonga, an Honor Flight to Washington D.C. with Veterans, or in local (Utah) communities working with marginalized populations (including incarcerated individuals, refugees, etc.). The students are required to complete 84 clinical hours and 84 culture hours (which involve exposure to local history, art, architecture, customs, etc.). As Faculty, we feel strongly that these public and global health experiences help cultivate cultural awareness in our students and prepare nurses who are better prepared to serve a diverse population of patients throughout their careers. This presentation will highlight our experiences and provide ideas for other nurse educators who have an interest in developing similar programs in their schools but do not know where to start. Suggestions about how to start building relationships that can lead to these opportunities, along with logistics for continuing the programs, will be highlighted.

Keywords: global health nursing, nursing education, clinical education, public health nursing

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5236 Awareness and Utilization of E-Learning Technologies in Teaching and Learning of Human Kinetics and Health Education Courses in Nigeria Universities

Authors: Ibrahim Laro ABUBAKAR

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The study examined the Availability and Utilization of E-Learning Technologies in Teaching of Human Kinetics and Health Education courses in Nigerian Universities, specifically, Universities in Kwara State. Two purposes were formulated to guide the study from which two research questions and two hypotheses were raised. The descriptive research design was used in the research. Three Hundred respondents (100 Lecturers and 200 Students) made up the population for the study. There was no sampling, as the population of the study was not much. A structured questionnaire tagged ‘Availability and Utilization of E-Learning Technologies in Teaching and Learning Questionnaire’ (AUETTLQ) was used for data collection. The questionnaire was subjected to face and content validation, and it was equally pilot tested. The validation yielded a reliability coefficient of 0.78. The data collected from the study were statistically analyzed using frequencies and percentage count for personal data of the respondents, mean and standard deviation to answer the research questions. The null hypotheses were tested at 0.05 level of significance using the independent t-test. One among other findings of this study showed that lecturers and Student are aware of synchronous e-learning technologies in teaching and learning of Human Kinetics and Health Education but often utilize the synchronous e-learning technologies. It was recommended among others that lecturers and Students should be sensitized through seminars and workshops on the need to maximally utilize available e-learning technologies in teaching and learning of Human Kinetics and Health Education courses in Universities.

Keywords: awareness, utilization, E-Learning, technologies, human kinetics synchronous

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5235 Safety of Mesenchymal Stem Cells Therapy: Potential Risk of Spontaneous Transformations

Authors: Katarzyna Drela, Miroslaw Wielgos, Mikolaj Wrobel, Barbara Lukomska

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Mesenchymal stem cells (MSCs) have a great potential in regenerative medicine. Since the initial number of isolated MSCs is limited, in vitro propagation is often required to reach sufficient numbers of cells for therapeutic applications. During long-term culture MSCs may undergo genetic or epigenetic alterations that subsequently increase the probability of spontaneous malignant transformation. Thus, factors that influence genomic stability of MSCs following long-term expansions need to be clarified before cultured MSCs are employed for clinical application. The aim of our study was to investigate the potential for spontaneous transformation of human neonatal cord blood (HUCB-MSCs) and adult bone marrow (BM-MSCs) derived MSCs. Materials and Methods: HUCB-MSCs and BM-MSCs were isolated by standard Ficoll gradient centrifugations method. Isolated cells were initially plated in high density 106 cells per cm2. After 48 h medium were changed and non-adherent cells were removed. The malignant transformation of MSCs in vitro was evaluated by morphological changes, proliferation rate, ability to enter cell senescence, the telomerase expression and chromosomal abnormality. Proliferation of MSCs was analyzed with WST-1 reduction method and population doubling time (PDT) was calculated at different culture stages. Then the expression pattern of genes characteristic for mesenchymal or epithelial cells, as well as transcriptions factors were examined by RT-PCR. Concomitantly, immunocytochemical analysis of gene-related proteins was employed. Results: Our studies showed that MSCs from all bone marrow isolations ultimately entered senescence and did not undergo spontaneous malignant transformation. However, HUCB-MSCs from one of the 15 donors displayed an increased proliferation rate, failed to enter senescence, and exhibited an altered cell morphology. In this sample we observed two different cell phenotypes: one mesenchymal-like exhibited spindle shaped morphology and express specific mesenchymal surface markers (CD73, CD90, CD105, CD166) with low proliferation rate, and the second one with round, densely package epithelial-like cells with significantly increased proliferation rate. The PDT of epithelial-like populations was around 1day and 100% of cells were positive for proliferation marker Ki-67. Moreover, HUCB-MSCs showed a positive expression of human telomerase reverse transcriptase (hTERT), cMYC and exhibit increased number of CFU during the long-term culture in vitro. Furthermore, karyotype analysis revealed chromosomal abnormalities including duplications. Conclusions: Our studies demonstrate that HUCB-MSCs are susceptible to spontaneous malignant transformation during long-term culture. Spontaneous malignant transformation process following in vitro culture has enormous effect on the biosafety issues of future cell-based therapies and regenerative medicine regimens.

Keywords: mesenchymal stem cells, spontaneous, transformation, long-term culture

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5234 Safety and Efficacy of Laparoscopic D2 Gastrectomy for Advanced Gastric Cancers Single Unit Experience

Authors: S. M. P Manjula, Ishara Amarathunga, Aryan Nath Koura, Jaideepraj Rao

Abstract:

Background: Laparoscopic D2 Gastrectomy for non metastatic advanced Gastric cancer (AGC) has become a controversial topic as there are confronting ideas from experts in the field. Lack of consensus are mainly due to non feasibility of the dissection and safety and efficacy. Method: Data from all D2 Gastrectomies performed (both Subtotal and Total Gastrectomies) in our unit from 2009 December to 2013 December were retrospectively analysed. Computor database was prospectively maintained. Pathological stage two A (iiA) and above considered advanced Gastric cancers, who underwent curative intent D2 Gastrectomy were included for analysis(n=46). Four patients excluded from the study as peritoneal fluid cytology came positive for cancer cells and one patient exempted as microscopic resection margin positive(R1) after curative resection. Thirty day morbidity and mortality, operative time, lymph nodes harvest and survival (disease free and overall) analyzed. Results: Complete curative resection achieved in 40 patients. Mean age of the study population was 62.2 (32-88) and male to female ratio was 23: 17. Thirty day mortality (1/40) and morbidity (6/40). Average operative time 203.7 minutes (185- 400) and average lymphnodes harvest was 40.5 (18-91). Disease free survival of the AGC in this study population was 16.75 months (1-49). Average hospital stay was 6.8 days (3-31). Conclusion: Laparoscopic dissection is effective feasible and safe in AGC.

Keywords: laparoscopy, advanced gastric cancer, safety, efficacy

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5233 Unifying RSV Evolutionary Dynamics and Epidemiology Through Phylodynamic Analyses

Authors: Lydia Tan, Philippe Lemey, Lieselot Houspie, Marco Viveen, Darren Martin, Frank Coenjaerts

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Introduction: Human respiratory syncytial virus (hRSV) is the leading cause of severe respiratory tract infections in infants under the age of two. Genomic substitutions and related evolutionary dynamics of hRSV are of great influence on virus transmission behavior. The evolutionary patterns formed are due to a precarious interplay between the host immune response and RSV, thereby selecting the most viable and less immunogenic strains. Studying genomic profiles can teach us which genes and consequent proteins play an important role in RSV survival and transmission dynamics. Study design: In this study, genetic diversity and evolutionary rate analysis were conducted on 36 RSV subgroup B whole genome sequences and 37 subgroup A genome sequences. Clinical RSV isolates were obtained from nasopharyngeal aspirates and swabs of children between 2 weeks and 5 years old of age. These strains, collected during epidemic seasons from 2001 to 2011 in the Netherlands and Belgium by either conventional or 454-sequencing. Sequences were analyzed for genetic diversity, recombination events, synonymous/non-synonymous substitution ratios, epistasis, and translational consequences of mutations were mapped to known 3D protein structures. We used Bayesian statistical inference to estimate the rate of RSV genome evolution and the rate of variability across the genome. Results: The A and B profiles were described in detail and compared to each other. Overall, the majority of the whole RSV genome is highly conserved among all strains. The attachment protein G was the most variable protein and its gene had, similar to the non-coding regions in RSV, more elevated (two-fold) substitution rates than other genes. In addition, the G gene has been identified as the major target for diversifying selection. Overall, less gene and protein variability was found within RSV-B compared to RSV-A and most protein variation between the subgroups was found in the F, G, SH and M2-2 proteins. For the F protein mutations and correlated amino acid changes are largely located in the F2 ligand-binding domain. The small hydrophobic phosphoprotein and nucleoprotein are the most conserved proteins. The evolutionary rates were similar in both subgroups (A: 6.47E-04, B: 7.76E-04 substitution/site/yr), but estimates of the time to the most recent common ancestor were much lower for RSV-B (B: 19, A: 46.8 yrs), indicating that there is more turnover in this subgroup. Conclusion: This study provides a detailed description of whole RSV genome mutations, the effect on translation products and the first estimate of the RSV genome evolution tempo. The immunogenic G protein seems to require high substitution rates in order to select less immunogenic strains and other conserved proteins are most likely essential to preserve RSV viability. The resulting G gene variability makes its protein a less interesting target for RSV intervention methods. The more conserved RSV F protein with less antigenic epitope shedding is, therefore, more suitable for developing therapeutic strategies or vaccines.

Keywords: drug target selection, epidemiology, respiratory syncytial virus, RSV

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5232 Child Rearing Styles and Family Communication Patterns among University Students

Authors: Pegah Farokhzad

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Family is a basic unit of the society and the main source of human development. The initial aim of the family is psychological and social support of its members and has special developmental stages. Researches show the families who have less cohesion, have more conflicts and maladjustments and the members of such families are not able to communicate effectively. Family is a system in which any inter communication is related to child rearing patterns and can affect it. Even the child rearing styles in childhood can determine the family communications in adulthood. Therefore, the aim of the present research was to examine the relationship between child-rearing styles including authoritative, authoritarian and permissive with dimensions of family communication patterns including the conversation and conformity. The research design was a correlational and the population consisted of the psychology students of Roudehen Islamic Azad University who were studying in academic year 2013-2014. A sample of 324 students were selected randomly from the population. The research tools were the Baumrind Child-rearing Questionnaires and Family Communication Patterns Inventory, The Revised Scale of Koerner and Fitzpatrick. The results were: (a) There was a positive and significant relationship between conversation orientation and authoritative style. (b) There was no significant relationship between conversation orientation and other child-rearing styles. (c) There was a negative significant relationship between conformity orientation and authoritative style. (d) There was a positive significant relationship between conformity orientation with authoritarian and permissive styles. (e) There was a significant relationship between 3 dimensions of child-rearing and communication patterns.

Keywords: child-rearing styles, family relationship patterns, university students, Iran

Procedia PDF Downloads 490