Search results for: smoking and attachment

Authors: JaeYoon Lee, Gi-Hoon Yang, JongHan Ha, MyungGu Yeo, SeungHyun Ahn, Hyeongjin Lee, HoJun Jeon, YongBok Kim, Minseong Kim, GeunHyung Kim

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One of the important factors in tissue engineering is to design optimal biomedical scaffolds, which can be governed by topographical surface characteristics, such as size, shape, and direction. Of these properties, we focused on the effects of nano- to micro-sized hierarchical surface. To fabricate the hierarchical surface structure on poly(ε-caprolactone) (PCL) film, we employed a micro-casting technique by pressing the mold and nano-etching technique using a modified plasma process. The micro-sized topography of PCL film was controlled by sizes of the micro structures on lotus leaf. Also, the nano-sized topography and hydrophilicity of PCL film were controlled by a modified plasma process. After the plasma treatment, the hydrophobic property of the PCL film was significantly changed into hydrophilic property, and the nano-sized structure was well developed. The surface properties of the modified PCL film were investigated in terms of initial cell morphology, attachment, and proliferation using osteoblast-like-cells (MG63). In particular, initial cell attachment, proliferation and osteogenic differentiation in the hierarchical structure were enhanced dramatically compared to those of the smooth surface. We believe that these results are because of a synergistic effect between the hierarchical structure and the reactive functional groups due to the plasma process. Based on the results presented here, we propose a new biomimetic surface model that maybe useful for effectively regenerating hard tissues.

Keywords: hierarchical surface, lotus leaf, nano-etching, plasma treatment

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Authors: Camilo Andres Agudelo-Velez, Lina María Martinez-Sanchez, Natalia Perilla-Hernandez, Maria De Los Angeles Rodriguez-Gazquez, Felipe Hernandez-Restrepo, Dayana Andrea Quintero-Moreno, Camilo Ruiz-Mejia, Isabel Cristina Ortiz-Trujillo, Monica Maria Zuluaga-Quintero

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Chronic obstructive pulmonary disease is common condition, characterized by a persistent blockage of airflow, partially reversible and progressive, that represents 5% of total deaths around the world, and it is expected to become the third leading cause of death by 2030. Objective: To establish the clinical and epidemiological profile of patients with chronic obstructive pulmonary disease in a medical institution from the city of Medellin, Colombia. Methods: A cross-sectional study was performed, with a sample of 50 patients with a diagnosis of chronic obstructive pulmonary disease in a private institution in Medellin, during 2015. The software SPSS vr. 20 was used for the statistical analysis. For the quantitative variables, averages, standard deviations, and maximun and minimun values were calculated, while for ordinal and nominal qualitative variables, proportions were estimated. Results: The average age was 73.5±9.3 years, 52% of the patients were women, 50% of them had retired, 46% ere married and 80% lived in the city of Medellín. The mean time of diagnosis was 7.8±1.3 years and 100% of the patients were treated at the internal medicine service. The most common clinical features were: 36% were classified as class D for the disease, 34% had a FEV1 <30%, 88% had a history of smoking and 52% had oxygen therapy at home. Conclusion: It was found that class D was the most common, and the majority of the patients had a history of smoking, indicating the need to strengthen promotion and prevention strategies in this regard.

Keywords: pulmonary disease, chronic obstructive, pulmonary medicine, oxygen inhalation therapy

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Authors: Amani Waheed, Adel Mishriky, Rasha Farouk, Essam Abdallah, Sarah Hussein

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Background: Occupational stress plays a crucial role in professional drivers' health. They are exposed to high workloads, low physical activity, high demand and low decisions as well as poor lifestyle factors including poor diet, sedentary work, and smoking. Dyslipidemia is a well-established modifiable cardiovascular risk factor. Occupational stress and other forms of chronic stress have been associated with raised levels of atherogenic lipids. Although stress management has some evidence in improving lipid profile, the association between occupational stress and dyslipidemia is not clear. Objectives: To assess the relational between occupational stress and lipid profile among professional drivers. Methodology: A cross-sectional study conducted at a large company in Ismailia City, Egypt, where, 131 professional drivers divided into 44 car drivers, 43 bus drivers, and 44 truck drivers were eligible after applying exclusion criteria. Occupational stress index (OSI), non-occupational risk factors of dyslipidemia were assessed using interview structured questionnaire. Blood pressure, body mass index (BMI) and lipid profile were measured. Results: The mean of total OSI score was 79.98 ± 6.14. The total OSI score is highest among truck drivers (82.16 ± 4.62), then bus drivers (80.26 ± 6.02) and lowest among car drivers (77.55 ± 6.79) with statistically significant. Eighty percent had Dyslipidemia. The duration of driving hours per day, exposure to passive smoking and increased BMI were the risk factors. No statistical significance between Total OSI score and dyslipidemia. Using, logistic regression analysis, occupational stress, duration of driving hours per day, and BMI were positive significant predictors for dyslipidemia. Conclusion: Professional drivers are exposed to occupational stress. A high proportion of drivers have dyslipidemia. Total OSI score doesn't have statistically significant relation with dyslipidemia.

Keywords: body mass index, dyslipidaemia, occupational stress, professional drivers

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Authors: Dileep Kumar Verma, Sunil Kumar Lal

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Influenza still remains one of the most challenging diseases posing significant threat to public health causing seasonal epidemics and pandemics. Influenza A Virus (IAV) surface protein hemagglutinin is known to play an important role in viral attachment to the host sialic acid receptors and concentrate in lipid rafts for efficient viral fusion. Selective nature of Influenza A virus to utilize rafts micro-domain for efficient virus assembly and budding has been explored in depth. However, the detailed mechanism of IAV binding to host cell membrane and entry into the host remains elusive. In the present study we investigated the role of lipid rafts in early life cycle events of IAV. Role of host lipid rafts was studied using raft disruption method by extraction of cholesterol by Methyl-β-Cyclodextrin. Using GM1, a well-known lipid raft marker, we were able to observe co-localization of IAV on lipid rafts on the host cell membrane. This experiment suggests a direct involvement of lipid rafts in the initiation of the IAV life cycle. Upon disruption of lipid rafts by Methyl-b-cyclodextrin, we observed a significant reduction in IAV binding on the host cell surface indicating a significant decrease in virus attachment to coherent membrane rafts. Our results provide proof that host lipid rafts and their constituents play an important role in the adsorption of IAV. This study opens a new avenues in IAV virus-host interactions to combat infection at a very early steps of the viral lifecycle.

Keywords: lipid raft, adsorption, cholesterol, methyl-β-cyclodextrin, GM1

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Authors: Kjellgren Maria, Lilliehorn Sara, Markström Urban

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This article describes the counselling practice of school social workers (SSWs) with individual children. SSWs work in the school system’s pupil health team, whose primary task is health promotion and prevention. The work of SSWs is about helping children and adolescents who, for various reasons, suffer from mental ill-health, school absenteeism, or stress that make them unable to achieve their intended goals. SSWs preferably meet these children in individual counselling sessions. The aim of this article is to describe and analyse SSWs’ experience of counselling with children and to examine the characteristics of counselling practice. The data collection was conducted through four semi-structured focus group interviews with a total of 22 SSWs in four different regions in Sweden. SSWs provide counselling to children in order to bring about improved feelings or behavioural changes. It can be noted that SSWs put emphasis on both the counselling process and the alliance with the child. The interviews showed a common practice among SSWs regarding the structure of the counselling sessions, with certain steps and approaches being employed. However, the specific interventions differed and were characterised by an eclectic standpoint in which SSWs utilise a broad repertoire of therapeutic schools and techniques. Furthermore, a relational perspective emerged as a most prominent focus for the SSWs by re-emerging throughout the material. We believe that SSWs could benefit from theoretical perspectives on ‘contextual model’ and ‘attachment theory’ as ‘models of the mind’. Being emotionally close to the child and being able to follow their development requires a lot from SSWs, as both professional caregivers and as “safe havens”.

Keywords: school social conselling, school social workers, contextual model, attachment thory

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Authors: Z. Honarvar, M. Farhoodi, M. R. Khani, S. Shojaee-Aliabadi

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Recently, edible films and coating have attracted much attention in food industry due to their environmentally friendly nature and safety in direct contact with food. However edible films have relatively weak mechanical properties and high water vapor permeability. Therefore, the aim of the study was to develop bilayer carboxymethyl cellulose (CMC) coated polypropylene (PP) films to increase mechanical properties and water vapor resistance of each pure CMC or PP films. To modify the surface properties of PE for better attachment of CMC coating layer to PP the atmospheric cold plasma treatment was used. Then the PP surface changes were evaluated by contact angle, AFM, and ATR-FTIR. Furthermore, the physical, mechanical, optical and microstructure characteristics of plasma-treated and untreated films were analyzed. ATR-FTIR results showed that plasma treatment created oxygen-containing groups on PP surface leading to an increase in hydrophilic properties of PP surface. Moreover, a decrease in water contact angle (from 88.92° to 52.15°) and an increase of roughness were observed on PP film surface indicating good adhesion between hydrophilic CMC and hydrophobic PP. Furthermore, plasma pre-treatment improved the tensile strength of CMC coated-PP films from 58.19 to 61.82. Water vapor permeability of plasma treated bilayer film was lower in comparison with untreated film. Therefore, cold plasma treatment has potential to improve attachment of CMC coating to PP layer, leading to enhanced water barrier and mechanical properties of CMC coated polypropylene as food packaging in which also CMC is in contact with food.

Keywords: carboxymethyl cellulose film, cold plasma, Polypropylene, surface properties

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Authors: Surekha Rathod

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Sickle cell disease is a vascular disorder characterized by chronic, ongoing organ damage that is punctuated by episodes of acutely painful vascular complications.1 It is the most common genetic blood disorder in the United States, with about 2000 infants being identified through routine blood screenings annually, and an estimated 104,000-138,000 affected individuals living in the United States. Approximately 0.3%-1.3% of African American are affected by Sickle Cell Diseases (SCD).3 The aim of this paper is to present oral health status of patients with SCD. A total of 200 subjects of both sexes in the age group 18- 40 years were included in this study. The subjects were examined and the following indices were recorded • Oral hygiene index – Simplified (OHI-S). • Probing depths (PD). • Clinical Attachment Levels (CAL). • Gingival Index - Loe and Sillness. • Turesky Gillmore Glickman Modification of the Quigley Hein Plaque Index. (1970) • DMFT index. • Sickle Cell Disease Severity Index. A total of 1478 patients were screened of which 200 subjects were found to be diagnosed with SCD by electrophoresis. The study thus, included 200 subjects (111 females & 89 males) diagnosed with Sickle Cell Disease in the age group of 18-40 years. The probing pocket depths (PPD) were measured in millimeters. 36% had PPD in the range of 2-4mm, 48% had PPD in the range of 4-6mm while 16% had PPD of more than 6mm. Similar results were obtained for the Clinical Attachment Levels (CAL). 29.5 % subjects had CAL 2-4mm, 44.5% had 4-6mm & 26% had CAL 6mm & above. We can thus conclude that although oral health is not a priority for patients with SCD, it is supported by increased plaque accumulation. Because of the chronic anemic state of the patients with SCD, they should be encouraged to pay strict attention to oral hygiene instructions and practice.

Keywords: chronic, genetic, oral, sickle cell disease, vascular

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Authors: Ishara Madusanka, So Morikawa

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Natural disasters, particularly floods, pose severe challenges globally, affecting both developed and developing countries. In many regions, especially Asia, riverine floods are prevalent and devastating. Integrated flood management incorporates structural and non-structural measures, with preventive relocation emerging as a cost-effective and proactive strategy for areas repeatedly impacted by severe flooding. However, preventive relocation is often hindered by economic, psychological, social, and institutional barriers. This study investigates the factors influencing resistance to preventive relocation and evaluates the role of flood risk information in shaping relocation decisions through risk perception. A conceptual model was developed, incorporating variables such as Flood Risk Information (FRI), Place Attachment (PA), Good Living Conditions (GLC), and Adaptation to Flooding (ATF), with Flood Risk Perception (FRP) serving as a mediating variable. The research was conducted in Welipitiya in the Polwatta river basin, Matara district, Sri Lanka, a region experiencing recurrent flood damage. For this study, an experimental design involving a structured questionnaire survey was utilized, with 185 households participating. The treatment group received flood risk information, including flood risk maps and historical data, while the control group did not. Data were collected in 2023 and analyzed using independent sample t-tests and Partial Least Squares Structural Equation Modeling (PLS-SEM). PLS-SEM was chosen for its ability to model latent variables, handle complex relationships, and suitability for exploratory research. Multi-group Analysis (MGA) assessed variations across different flood risk areas. Findings indicate that flood risk information had a limited impact on flood risk perception and relocation decisions, though its effect was significant in specific high-risk areas. Place attachment was a significant factor influencing relocation decisions across the sample. One potential reason for the limited impact of flood risk information on relocation decisions could be the lack of specificity in the information provided. The results suggest that while flood risk information alone may not significantly influence relocation decisions, it is crucial in specific contexts. Future studies and practitioners should focus on providing more detailed risk information and addressing psychological factors like place attachments to enhance preventive relocation efforts.

Keywords: flood risk communication, flood risk perception, place attachment, preventive relocation, structural equation modeling

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Authors: Hadjer Didouh, Izzaddine Sameut Bouhaik, Mohammed Hadj Meliani

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This research delves into the intricate dynamics of biofilm adhesion on surfaces, particularly focusing on the widely employed X52 surface in oil and gas industry pipelines. Biofilms, characterized by microorganisms within a self-produced matrix, pose significant challenges due to their detrimental impact on surfaces. Our study integrates advanced molecular techniques and cutting-edge microscopy, such as scanning electron microscopy (SEM), to identify microbial communities and visually assess biofilm adhesion. Simultaneously, we concentrate on the X52 surface, utilizing impedance spectroscopy and potentiodynamic polarization to gather electrochemical responses under various conditions. In conjunction with the broader investigation, we propose a novel approach to mitigate biofilm-induced corrosion challenges. This involves environmentally friendly inhibitors derived from plants, offering a sustainable alternative to conventional chemical treatments. Our inquiry screens and selects inhibitors based on their efficacy in hindering biofilm formation and reducing corrosion rates on the X52 surface. This study contributes valuable insights into the interplay between electrochemical processes and biofilm attachment on the X52 surface. Furthermore, the outcomes of this research have broader implications for the oil and gas industry, where biofilm-related corrosion is a persistent concern. The exploration of eco-friendly inhibitors not only holds promise for corrosion control but also aligns with environmental considerations and sustainability goals. The comprehensive nature of this research aims to enhance our understanding of biofilm dynamics, provide effective strategies for corrosion mitigation, and contribute to sustainable practices in pipeline management within the oil and gas sector.

Keywords: bio-corrosion, biofilm, attachment, X52, metal/bacteria interface

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Authors: Cristy Stagnar, Nina Hubig, Diana Ivankovic

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The epigenome is a compelling candidate for mediating long-term responses to environmental effects modifying disease risk. The main goal of this research is to develop a machine learning-based DNA methylation score, which will be valuable in delineating the unique contribution of paternal epigenetic modifications to the germline impacting childhood health outcomes. It will also be a useful tool in validating self-reports of nonsmoking and in adjusting epigenome-wide DNA methylation association studies for this early-life exposure. Using secondary data from two population-based methylation profiling studies, our DNA methylation score is based on CpG DNA methylation measurements from cord blood gathered from children whose fathers smoked pre- and peri-conceptually. Each child’s mother and father fell into one of three class labels in the accompanying questionnaires -never smoker, former smoker, or current smoker. By applying different machine learning algorithms to the accessible resource for integrated epigenomic studies (ARIES) sub-study of the Avon longitudinal study of parents and children (ALSPAC) data set, which we used for training and testing of our model, the best-performing algorithm for classifying the father smoker and mother never smoker was selected based on Cohen’s κ. Error in the model was identified and optimized. The final DNA methylation score was further tested and validated in an independent data set. This resulted in a linear combination of methylation values of selected probes via a logistic link function that accurately classified each group and contributed the most towards classification. The result is a unique, robust DNA methylation score which combines information on DNA methylation and early life exposure of offspring to paternal smoking during pregnancy and which may be used to examine the paternal contribution to offspring health outcomes.

Keywords: epigenome, health outcomes, paternal preconception environmental exposures, supervised machine learning

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Authors: Simone Tedeschi, Francesco Crespi, Paolo Liberati, Massimo Paradiso, Antonio Sciala

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This paper aims at contributing to the understanding of smokers’ responses to cigarette prices increases with a focus on heterogeneity, both across individuals and price levels. To do this, a stated preference quasi-experimental design grounded in a random utility framework is proposed to evaluate the effect on smokers’ utility of the price level and variation, along with social conditioning and health impact perception. The analysis is based on individual-level data drawn from a unique survey gathering very detailed information on Italian smokers’ habits. In particular, qualitative information on the individual reactions triggered by changes in prices of different magnitude and composition are exploited. The main findings stemming from the analysis are the following; the average price elasticity of cigarette consumption is comparable with previous estimates for advanced economies (-.32). However, the decomposition of this result across five latent-classes of smokers, reveals extreme heterogeneity in terms of price responsiveness, implying a potential price elasticity that ranges between 0.05 to almost 1. Such heterogeneity is in part explained by observable characteristics such as age, income, gender, education as well as (current and lagged) smoking intensity. Moreover, price responsiveness is far from being independent from the size of the prospected price increase. Finally, by comparing even and uneven price variations, it is shown that uniform across-brand price increases are able to limit the scope of product substitutions and downgrade. Estimated price-response heterogeneity has significant implications for tax policy. Among them, first, it provides evidence and a rationale for why the aggregate price elasticity is likely to follow a strictly increasing pattern as a function of the experienced price variation. This information is crucial for forecasting the effect of a given tax-driven price change on tax revenue. Second, it provides some guidance on how to design excise tax reforms to balance public health and revenue goals.

Keywords: smoking behaviour, preference heterogeneity, price responsiveness, cigarette taxation, random utility models

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Authors: Humaira Mujeeb, Farah Qadir

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The present study aimed to explore the association between interpersonal relationship and postpartum depression with a special focus on gender of the infant among women in Gilgit, Gilgit-Baltistan, Pakistan. The research was quantitative in nature. It was a correlation study with a cross-sectional study design. The target population was women between six weeks to six months after the delivery of a baby. The sample size of 158 women has been computed by using G*Power (3.0.10 version). The sample was taken through quota sampling technique which was used to gather data according to the specifically predefined groups (79 women with female infants and 79 women with male infants). The sample was selected non-randomly according to the fixed quota. A protocol which had demographic and interpersonal relationship variables alongside with the Urdu version Edinburgh postnatal depression scale was used to collect the relevant data. The data was analyzed by using SPSS 16.0 software package. A statistically significant association between the attachment with husband in women who had a female infant and postpartum depression has been found. The association between the husband’s emotional and physical support in women who had a female infant and postpartum depression had also been found significant. In case of women with a male infant, the association between support of in-laws and postpartum depression is statistically significant. An association between the violence/discrimination based on the basis of infant's gender in women who had a female infant and postpartum depression is also found. These findings points out that when studying the correlates of postpartum depression, it is imperative to carry out an analysis in the context of gender by considering gender of the infant especially in societies where strict gender preferences exists.

Keywords: infant, gender, attachment, husband, in-laws, support, violence, discrimination, Edinburgh postnatal depression scale, Gilgit, Pakistan

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Authors: Ripon Sarkar, Kabita Chaterjee, Ananya Barui

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Smoking is one of the leading causes of oral cancer. Cigarette smoke affects various cellular parameters and alters molecular metabolism of cells. Epithelial cells losses their cytoskeleton structure, membrane integrity, cellular polarity that subsequently initiates the process of epithelial cells to mesenchymal transition due to long exposure of cigarette smoking. It changes the normal cellular metabolic activity which induces oxidative stress and enhances the reactive oxygen spices (ROS) formation. Excessive ROS and associated oxidative stress are considered to be a driving force in alteration in cellular phenotypes, polarity distribution and mitochondrial metabolism. Noninvasive assessment of such parameters plays essential role in development of routine screening system for early diagnosis of oral cancer. Electrical cell-substrate impedance sensing (ECIS) is one of such method applied for detection of cellular membrane impedance which can be correlated to cell membrane integrity. Present study intends to explore the alteration in cellular impedance along with the expression of cellular polarity molecules and cytoskeleton distributions in oral epithelial cells of habitual smokers and to correlate the outcome to that of clinically diagnosed oral leukoplakia and oral squamous cell carcinoma patients. Total 80 subjects were categorized into four study groups: nonsmoker (NS), cigarette smoker (CS), oral leukoplakia (OLPK) and oral squamous cell carcinoma (OSCC). Cytoskeleton distribution was analyzed by staining of actin filament and generation of ROS was measured using assay kit using standard protocol. Cell impedance was measured through ECIS method at different frequencies. Expression of E-cadherin and protease-activated receptor (PAR) proteins were observed through immune-fluorescence method. Distribution of actin filament is well organized in NS group however; distribution pattern was grossly varied in CS, OLPK and OSCC. Generation of ROS was low in NS which subsequently increased towards OSCC. Expressions of E-cadherin and change in cellular electrical impedance in different study groups indicated the hallmark of cancer progression from NS to OSCC. Expressions of E-cadherin, PAR protein, and cell impedance were decreased from NS to CS and farther OSCC. Generally, the oral epithelial cells exhibit apico-basal polarity however with cancer progression these cells lose their characteristic polarity distribution. In this study expression of polarity molecule and ECIS observation indicates such altered pattern of polarity among smoker group. Overall the present study monitored the alterations in intracellular ROS generation and cell metabolic function, membrane integrity in oral epithelial cells in cigarette smokers. Present study thus has clinical significance, and it may help in developing a noninvasive technique for early diagnosis of oral cancer amongst susceptible individuals.

Keywords: cigarette smoking, early oral cancer detection, electric cell-substrate impedance sensing, noninvasive screening

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Authors: Omid Giahi, Ebrahim Darvishi, Mahdi Akbarzadeh

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Introduction: Occupational low back pain (LBP) is one of the most prevalent work-related musculoskeletal disorders in which a lot of risk factors are involved that. The present study focuses on the relation between personal, psycho-social and occupational risk factors and LBP severity in industrial workers. Materials and Methods: This research was a case-control study which was conducted in Kurdistan province. 100 workers (Mean Age ± SD of 39.9 ± 10.45) with LBP were selected as the case group, and 100 workers (Mean Age ± SD of 37.2 ± 8.5) without LBP were assigned into the control group. All participants were selected from various industrial units, and they had similar occupational conditions. The required data including demographic information (BMI, smoking, alcohol, and family history), occupational (posture, mental workload (MWL), force, vibration and repetition), and psychosocial factors (stress, occupational satisfaction and security) of the participants were collected via consultation with occupational medicine specialists, interview, and the related questionnaires and also the NASA-TLX software and REBA worksheet. Chi-square test, logistic regression and structural equation modeling (SEM) were used to analyze the data. For analysis of data, IBM Statistics SPSS 24 and Mplus6 software have been used. Results: 114 (77%) of the individuals were male and 86 were (23%) female. Mean Career length of the Case Group and Control Group were 10.90 ± 5.92, 9.22 ± 4.24, respectively. The statistical analysis of the data revealed that there was a significant correlation between the Posture, Smoking, Stress, Satisfaction, and MWL with occupational LBP. The odds ratios (95% confidence intervals) derived from a logistic regression model were 2.7 (1.27-2.24) and 2.5 (2.26-5.17) and 3.22 (2.47-3.24) for Stress, MWL, and Posture, respectively. Also, the SEM analysis of the personal, psycho-social and occupational factors with LBP revealed that there was a significant correlation. Conclusion: All three broad categories of risk factors simultaneously increase the risk of occupational LBP in the workplace. But, the risks of Posture, Stress, and MWL have a major role in LBP severity. Therefore, prevention strategies for persons in jobs with high risks for LBP are required to decrease the risk of occupational LBP.

Keywords: industrial workers occupational, low back pain, occupational risk factors, psychosocial factors

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Authors: M. Nekri, A. Khelladi

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The world wide web network is a network with a complex topology, the main properties of which are the distribution of degrees in power law, A low clustering coefficient and a weak average distance. Modeling the web as a graph allows locating the information in little time and consequently offering a help in the construction of the research engine. Here, we present a model based on the already existing probabilistic graphs with all the aforesaid characteristics. This work will consist in studying the web in order to know its structuring thus it will enable us to modelize it more easily and propose a possible algorithm for its exploration.

Keywords: clustering coefficient, preferential attachment, small world, web community

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Authors: Mahboubeh Kabiri, Saba Aslani

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Among various approaches used for the treatment of cardiovascular diseases, the occlusion of the small-diameter vascular graft (SDVG) is still an unresolved problem which seeks further research to address them. Though autografts are now the gold standards to be replaced for blocked coronary arteries, they suffer from inadequate quality and quantity. On the other hand, the major problems of the tissue engineered grafts are thrombosis and intimal hyperplasia. Provision of a suitable spatiotemporal release pattern of anticoagulant agents such as heparin and aspirin can be a step forward to overcome such issues . Herein, we fabricated electrospun scaffolds from FDA (Food and Drug Administration) approved poly-L-lactic acid (PLLA) with aspirin loaded into the nanofibers. Also, we surface coated the scaffolds with Amniotic Membrane lysate as a source for natural elastic polymers and a mimic of endothelial basement membrane. The scaffolds were characterized thoroughly structurally and mechanically for their morphology, fiber orientation, tensile strength, hydrophilicity, cytotoxicity, aspirin release and cell attachment support. According to the scanning electron microscopy (SEM) images, the size of fibers ranged from 250 to 500 nm. The scaffolds showed appropriate tensile strength expected for vascular grafts. Cellular attachment, growth, and infiltration were proved using SEM and MTT (3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide) assay. Drug-loaded scaffolds showed a sustained release profile of aspirin in 7 days. An enhanced cytocompatibility was observed in AM-coated electrospun PLLA fibers compared to uncoated scaffolds. Our results together indicated that AM lysate coated ASA releasing scaffolds have promising potentials for development of a biocompatible SDVG.

Keywords: vascular tissue engineering, vascular grafts, anticoagulant agent, aspirin, amniotic membrane

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Authors: John W. Travis

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There is an epidemic of couples separating after a child is born into a family, generally with the father leaving emotionally or physically in the first few years after birth. This separation creates high levels of stress for both parents, especially the primary parent, leaving her (or him) less available to the infant for healthy attachment and nurturing. The deterioration of the couple’s bond leaves parents increasingly under-resourced, and the dependent child in a compromised environment, with an increased likelihood of developing an attachment disorder. Objectives: To understand the dynamics of a couple, once the additional and extensive demands of a newborn are added to a nuclear family structure, and to identify effective ways to support all members of the family to thrive. Qualitative studies interviewed men, women, and couples after pregnancy and the early years as a family, regarding key destructive factors, as well as effective tools for the couple to retain a strong bond. In-depth analysis of a few cases, including the author’s own experience, reveal deeper insights about subtle factors, replicated in wider studies. Using a self-assessment survey, many fathers report feeling abandoned, due to the close bond of the mother-baby unit, and in turn, withdrawing themselves, leaving the mother without support and closeness to resource her for the baby. Fathers report various types of abandonment, from his partner to his mother, with whom he did not experience adequate connection as a child. The study identified a key destructive factor to be unrecognized wounding from childhood that was carried into the relationship. The study culminated in the naming of Male Postpartum Abandonment Syndrome (MPAS), describing the epidemic in industrialized cultures with the nuclear family as the primary configuration. A growing family system often collapses without a minimum number of adult caregivers per infant, approximately four per infant (3.87), which allows for proper healing and caretaking. In cases with no additional family or community beyond one or two parents, the layers of abandonment and trauma result in the deterioration of a couple’s relationship and ultimately the family structure. The solution includes engaging community in support of new families. The study identified (and recommends) specific resources to assist couples in recognizing and healing trauma and disconnection at multiple levels. Recommendations include wider awareness and availability of resources for healing childhood wounds and greater community-building efforts to support couples for the whole family to thrive.

Keywords: abandonment, attachment, community building, family and marital functioning, healing childhood wounds, infant wellness, intimacy, marital satisfaction, relationship quality, relationship satisfaction

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Authors: Sneha Kumari, Ravi Krishnan Elangovan

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This abstract describes the development of a high-speed tracking method by modification in motor components for nanoparticle attachment. Myosin motors are nano-sized protein machines powering movement that defines life. These miniature molecular devices serve as engines utilizing chemical energy stored in ATP to produce useful mechanical energy in the form of a few nanometre displacement events leading to force generation that is required for cargo transport, cell division, cell locomotion, translated to macroscopic movements like running etc. With the advent of in vitro motility assay (IVMA), detailed functional studies of the actomyosin system could be performed. The major challenge with the currently available IVMA for tracking actin filaments is a resolution limitation of ± 50nm. To overcome this, we are trying to develop Single Molecule IVMA in which nanoparticle (GNP/QD) will be attached along or on the barbed end of actin filaments using CapZ protein and visualization by a compact TIRF module called ‘cTIRF’. The waveguide-based illumination by cTIRF offers a unique separation of excitation and collection optics, enabling imaging by scattering without emission filters. So, this technology is well equipped to perform tracking with high precision in temporal resolution of 2ms with significantly improved SNR by 100-fold as compared to conventional TIRF. Also, the nanoparticles (QD/GNP) attached to actin filament act as a point source of light coffering ease in filament tracking compared to conventional manual tracking. Moreover, the attachment of cargo (QD/GNP) to the thin filament paves the way for various nano-technological applications through their transportation to different predetermined locations on the chip

Keywords: actin, cargo, IVMA, myosin motors and single-molecule system

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Authors: M. Sazali Said, Rahim Jamian, Shahrizan Yusoff, Shahruzaman Sulaiman, Jum'Azulhisham Abdul Shukor

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This case study focuses on the role of Universiti Kuala Lumpur Malaysian Spanish Institute (UniKL MSI) to produce technologist in order to reduce the shortage of skilled workers especially in the automotive industry. The purpose of the study therefore seeks to examine the effectiveness of Technical Education and Vocational Training (TEVT) curriculum of UniKL MSI to produce graduates that could immediately be productively employed by the automotive industry. The approach used in this study is through performance evaluation of students attending the Industrial Training Attachment (INTRA). The sample of study comprises of 37 students, 16 university supervisors and 26 industrial supervisors. The research methodology involves the use of quantitative and qualitative methods of data collections through the triangulation approach. The quantitative data was gathered from the students, university supervisors and industrial supervisors through the use of questionnaire. Meanwhile, the qualitative data was obtained from the students and university supervisors through the use of interview and observation. Both types of data have been processed and analyzed in order to summarize the results in terms of frequency and percentage by using a computerized spread sheet. The result shows that industrial supervisors were satisfied with the students’ performance. Meanwhile, university supervisors rated moderate effectiveness of the UniKL MSI curriculum in producing graduates with appropriate skills and in meeting the industrial needs. During the period of study, several weaknesses in the curriculum have been identified for further continuous improvements. Recommendations and suggestions for curriculum improvement also include the enhancement of technical skills and competences of students towards fulfilling the needs and demand of the automotive industries.

Keywords: technical education and vocational training (TEVT), industrial training attachment (INTRA), curriculum improvement, automotive industry

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Authors: Dileep K. Verma, Sunil K. Lal

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Influenza still remains one of the most challenging diseases posing significant threat to public health causing seasonal epidemics and pandemics. Previous studies suggest that influenza hemagglutinin is essential for viral attachment to host sialic acid receptors and concentrate in lipid rafts for efficient viral fusion. Studies also reported selective nature of Influenza virus to utilize rafts micro-domain for efficient virus assembly and budding. However, the detailed mechanism of Influenza A Virus (IAV) binding to host cell membrane and entry inside the host remains elusive. In the present study, we investigated if host membrane lipid rafts play any significant role in early life cycle events of influenza A virus. Role of host lipid rafts was studied using raft disruption method by extraction of cholesterol and Methyl-β-Cyclodextrin was used to remove membrane cholesterol. We observed co-localization of Influenza A Virus to lipid rafts by visualization of known lipid raft marker GM1 on host cell membrane. Co-localization suggest direct involvement of these micro-domain in initiation of IAV life cycle. We found significant reduction in influenza A virus adsorption in raft disrupted target host cells indicating poor binding and attachment in absence of coherent membrane rafts. Taken together, the results of present study provide evidence for critical involvement of host lipid rafts and its constituents in adsorption process of Influenza A Virus and suggests crucial involvement in other early events of IAV life cycle. The present study opens a new domain to study influenza virus-host interaction and to combat flu at the very early steps of viral life cycle.

Keywords: lipid raft, adsorption, cholesterol, methyl-β-cyclodextrin, GM1

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Authors: Ling-Ling E, Lin Feng, Hong-Chen Liu, Dong-Sheng Wang, Zhanping Shi, Juncheng Wang, Wei Luo, Yan Lv

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The objective of this study was to compare the effects of the two calcium phosphate composite scaffolds on the attachment, proliferation and osteogenic differentiation of rabbit dental pulp stem cells (DPSCs). One nano-hydroxyapatite/collagen/poly (L-lactide) (nHAC/PLA), imitating the composition and the micro-structure characteristics of the natural bone, was made by Beijing Allgens Medical Science & Technology Co., Ltd. (China). The other beta-tricalcium phosphate (β-TCP), being fully interoperability globular pore structure, was provided by Shanghai Bio-lu Biomaterials Co, Ltd. (China). We compared the absorption water rate and the protein adsorption rate of two scaffolds and the characterization of DPSCs cultured on the culture plate and both scaffolds under osteogenic differentiation media (ODM) treatment. The constructs were then implanted subcutaneously into the back of severe combined immunodeficient (SCID) mice for 8 and 12 weeks to compare their bone formation capacity. The results showed that the ODM-treated DPSCs expressed osteocalcin (OCN), bone sialoprotein (BSP), type I collagen (COLI) and osteopontin (OPN) by immunofluorescence staining. Positive alkaline phosphatase (ALP) staining, calcium deposition and calcium nodules were also observed on the ODM-treated DPSCs. The nHAC/PLA had significantly higher absorption water rate and protein adsorption rate than ß-TCP. The initial attachment of DPSCs seeded onto nHAC/PLA was significantly higher than that onto ß-TCP; and the proliferation rate of the cells was significantly higher than that of ß-TCP on 1, 3 and 7 days of cell culture. DPSCs+ß-TCP had significantly higher ALP activity, calcium/phosphorus content and mineral formation than DPSCs+nHAC/PLA. When implanted into the back of SCID mice, nHAC/PLA alone had no new bone formation, newly formed mature bone and osteoid were only observed in β-TCP alone, DPSCs+nHAC/PLA and DPSCs+β-TCP, and this three groups displayed increased bone formation over the 12-week period. The percentage of total bone formation area had no difference between DPSCs+β-TCP and DPSCs+nHAC/PLA at each time point，but the percentage of mature bone formation area of DPSCs+β-TCP was significantly higher than that of DPSCs+nHAC/PLA. Our results demonstrated that the DPSCs on nHAC/PLA had a better proliferation and that the DPSCs on β-TCP had a more mineralization in vitro, much more newly formed mature bones in vivo were presented in DPSCs+β-TCP group. These findings have provided a further knowledge that scaffold architecture has a different influence on the attachment, proliferation and differentiation of cells. This study may provide insight into the clinical periodontal bone tissue repair with DPSCs+β-TCP construct.

Keywords: dental pulp stem cells, nano-hydroxyapatite/collagen/poly(L-lactide), beta-tricalcium phosphate, periodontal tissue engineering, bone regeneration

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Authors: Sharon Waichman, Shahaf Froim, Ido Zukerman, Shmuel Barzilai, Shmual Hayun, Avi Raveh

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Boron carbide is a ceramic material with superior properties such as high chemical and thermal stability, high hardness and high wear resistance. Moreover, it has a big cross section for neutron absorption and therefore can be employed in nuclear based applications. However, an efficient attachment of boron carbide to a metal such as aluminum can be very challenging, mainly because of the formation of aluminum-carbon bonds that are unstable in humid environment, the affinity of oxygen to the metal and the different thermal expansion coefficients of the two materials that may cause internal stresses and a subsequent failure of the bond. Here, we aimed to achieving a strong and a durable attachment between the boron carbide coating and the aluminum substrate. For this purpose, we applied Ti as a thin intermediate layer that provides a gradual change in the thermal expansion coefficients of the configured layers. This layer is continuous and therefore prevents the formation of aluminum-carbon bonds. Boron carbide coatings with a thickness of 1-5 µm were deposited on the aluminum substrate by pulse-DC magnetron sputtering. Prior to the deposition of the boron carbide layer, the surface was pretreated by energetic ion plasma followed by deposition of the Ti intermediate adhesive layer in a continuous process. The properties of the Ti intermediate layer were adjusted by the bias applied to the substrate. The boron carbide/aluminum bond was evaluated by various methods and complementary techniques, such as SEM/EDS, XRD, XPS, FTIR spectroscopy and Glow Discharge Spectroscopy (GDS), in order to explore the structure, composition and the properties of the layers and to study the adherence mechanism of the boron carbide/aluminum contact. Based on the interfacial bond characteristics, we propose a desirable solution for improved adhesion of boron carbide to aluminum using a highly efficient intermediate adhesive layer.

Keywords: adhesion, boron carbide coatings, ceramic/metal bond, intermediate layer, pulsed-DC magnetron sputtering

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Authors: Timmis W., Simms M., Thomas C.

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This case discusses the management of two floors of mouth (FOM) Squamous Cell Carcinomas (SCC) not identified upon initial biopsy. A 51 year-old male presented with right FOM erythroleukoplakia. Relevant medical history included alcoholic dependence syndrome and alcoholic liver disease. Relevant drug therapy encompassed acamprosate, folic acid, hydroxocobalamin and thiamine. The patient had a 55.5 pack-year smoking history and alcohol dependence from age 14, drinking 16 units/day. FOM incisional biopsy and histopathological analysis diagnosed Carcinoma in situ. Treatment involved wide local excision. Specimen analysis revealed two separate foci of pT1 moderately differentiated SCCs. Carcinoma staging scans revealed no pathological lymphadenopathy, no local invasion or metastasis. SCCs had been excised in completion with narrow margins. MDT discussion concluded that in view of the field changes it would be difficult to identify specific areas needing further excision, although techniques such as Lugol’s Iodine were considered. Further surgical resection, surgical neck management and sentinel lymph node biopsy was offered. The patient declined intervention, primary management involved close monitoring alongside alcohol and smoking cessation referral. Narrow excisional margins can increase carcinoma recurrence risk. Biopsy failed to identify SCCs, despite sampling an area of clinical concern. For gross field change multiple incisional biopsies should be considered to increase chance of accurate diagnosis and appropriate treatment. Coupling of tobacco and alcohol has a synergistic effect, exponentially increasing the relative risk of oral carcinoma development. Tobacco and alcoholic control is fundamental in reducing treatment‑related side effects, recurrence risk and second primary cancer development.

Keywords: alcohol dependence, biopsy, oral carcinoma, tobacco

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Authors: Anuj Kumar, Kummara M. Rao, Sung S. Han

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Bone tissue engineering has emerged as a potentially alternative method for localized bone defects or diseases, congenital deformation, and surgical reconstruction. The designing and the fabrication of the ideal scaffold is a great challenge, in restoring of the damaged bone tissues via cell attachment, proliferation, and differentiation under three-dimensional (3D) biological micro-/nano-environment. In this case, hydrogel system composed of high hydrophilic 3D polymeric-network that is able to mimic some of the functional physical and chemical properties of the extracellular matrix (ECM) and possibly may provide a suitable 3D micro-/nano-environment (i.e., resemblance of native bone tissues). Thus, this proposed hydrogel system is highly permeable and facilitates the transport of the nutrients and metabolites. However, the use of hydrogels in bone tissue engineering is limited because of their low mechanical properties (toughness and stiffness) that continue to posing challenges in designing and fabrication of tough and stiff hydrogels along with improved bioactive properties. For this purpose, in our lab, polyacrylamide-based hybrid hydrogels were synthesized by involving sodium alginate, cellulose nanocrystals and silica-based glass using one-step free-radical polymerization. The results showed good in vitro apatite-forming ability (biomineralization) and improved mechanical properties (under compression in the form of strength and stiffness in both wet and dry conditions), and in vitro osteoblastic (MC3T3-E1 cells) cytocompatibility. For in vitro cytocompatibility assessment, both qualitative (attachment and spreading of cells using FESEM) and quantitative (cell viability and proliferation using MTT assay) analyses were performed. The obtained hybrid hydrogels may potentially be used in bone tissue engineering applications after establishment of in vivo characterization.

Keywords: bone tissue engineering, cellulose nanocrystals, hydrogels, polyacrylamide, sodium alginate

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Authors: John Toussaint

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Objective: Our society is suffering from an epidemic of body image dissatisfaction, and related disorders appear to be increasing globally for children. There is much to indicate that children's body image and eating attitudes are being affected negatively by socio-cultural factors such as parents, peers and media. Most studies and theories, however, have focused extensively on the daughter-mother relationship. Very few studies have investigated the role of attachment to the father as an important factor in the development of girls’ and women’s attitudes towards themselves and their bodies. Recently, data have shown that the father’s parenting style, as well as the quality of the relationship with him is crucial for the understanding of the development and persistence of body image disorders. This presentation is based on samples of participants with self-defined body image dissatisfaction, and the self-reported measures of their fathers’ parental behaviours, emotional warmth, support, or protection. Attachment theory does offer support in exploring these relationships and it is used in this presentation to assist in understanding the relationship between the father and his daughter in relation to body image and mental health. Clinical implications are also offered in respect to work with body image, eating disorders and relational therapy. Methods: As awareness of the increasing frequency of body image concerns in children grows, so too does the need for a simple, valid and reliable measure of body image. The Children's Body Image Scale (CBIS) designed in Australia, depicts seven male and females figures from which children are to choose their perceived body type and ideal body type. This was compared with a range of international body mass index (BMI) reference standards. These measures together with individual one-on-one interviews were completed by 158 children aged 7-12 years. Results: A high frequency of body image dissatisfaction was indicated in the children's responses. 55% of girls and 41% of boys said they would like to be thinner, and wished for an ideal BMI figure below the 10th percentile. This is an unhealthy and unattainable level of body fatness for the majority of children when considered in relation to the reported secular trend of their increasing average body size. Thin children were generally ranked as best and perceived as kind, happy, academically skilled, and socially successful. Fat children were perceived as unintelligent, lazy, greedy, unpopular, and unable to play physical games. Conclusions: Body image ideals and fat stereotypes are well entrenched among children. There is much to indicate that children's body image and eating attitudes are being affected negatively by sociocultural factors such as parents, peers and media. Teachers and health professionals could promote intervention programs for children involving knowledge and acceptance of genetic influences on body type; the dangerous effects of weight loss dieting; the importance of physical activity and eating healthy; and scepticism and critical analysis of mass media messages.

Keywords: body image, father attachment, mental health, eating disorders

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Authors: Catharina Dwi Astuti Depari, Gregorius Agung Setyonugroho

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In concern for human safety, living in disaster-prone areas is twofold: it is profoundly cataclysmic yet perceptibly contributive. This paradox could be identified in Kalitengah Lor Sub-village community who inhabit Mount Merapi’s most hazardous area, putting them to the highest exposure to eruptions’ cataclysmic impacts. After the devastating incident in 2010, through the Action Plan for Rehabilitation and Reconstruction, the National Government with immediate aid from humanitarian agencies initiated a relocation program by establishing nearly 2,613 temporary shelters throughout the mountain’s region. The problem arose as some of the most affected communities including those in Kalitengah Lor Sub-village, persistently refused to relocate. The obnoxious experience of those living in temporary shelters resulted from the program’s failure to support a long-term living was assumed to instigate the rejection. From the psychological standpoint, this phenomenon reflects the emotional bond between the affected communities with their former dwellings. Regarding this, the paper aims to reveal the factors influencing the emotional attachment of Kalitengah Lor community to their former dwellings including the dwellings’ spatial design transformation prior and post the eruption in 2010. The research adopted Likert five scale-questionnaire comprising a wide range of responses from strongly agree to strongly disagree. The responses were then statistically measured, leading to consensus that provides bases for further interpretations toward the local’s characteristics. Using purposive unit sampling technique, 50 respondents from 217 local households were randomly selected. Questions in the questionnaire were developed with concerns on the aspects of place attachment concept: affection, cognitive, behavior, and perception. Combined with quantitative method, the research adopted diachronic method which was aimed to analyze the spatial design transformation of each dwelling in relation to the inhabitant’s daily activities and personal preferences. The research found that access to natural resources like sand mining, agricultural farms and wood forests, social relationship and physical proximity from house to personal asset like cattle shed, are the dominant factors encouraging the locals to emotionally attached to their former dwellings. Consequently, each dwelling’s spatial design is suffered from changes in which the current house is typically larger in dimension and the bathroom is replaced by public toilet located outside the house’s backyard. Relatively unchanged, the cattle shed is still located in front of the house, the continuous visual relationship, particularly between the living and family room, is maintained, as well as the main orientation of the house towards the local street.

Keywords: diachronic method, former dwellings, local’s characteristics, place attachment, spatial design transformation

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Authors: Adel Dalilottojari, Bahman Delalat, Frances J. Harding, Michaelia P. Cockshell, Claudine S. Bonder, Nicolas H. Voelcker

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Endothelial Progenitor Cell (EPC) based therapies continue to be of interest to treat ischemic events based on their proven role to promote blood vessel formation and thus tissue re-vascularisation. Current strategies for the production of clinical-grade EPCs requires the in vitro isolation of EPCs from peripheral blood followed by cell expansion to provide sufficient quantities EPCs for cell therapy. This study aims to examine the use of different biomolecules to significantly improve the current strategy of EPC capture and expansion on collagen type I (Col I). In this study, four different biomolecules were immobilised on a surface and then investigated for their capacity to support EPC capture and proliferation. First, a cell microarray platform was fabricated by coating a glass surface with epoxy functional allyl glycidyl ether plasma polymer (AGEpp) to mediate biomolecule binding. The four candidate biomolecules tested were Col I, collagen type II (Col II), collagen type IV (Col IV) and vascular endothelial growth factor A (VEGF-A), which were arrayed on the epoxy-functionalised surface using a non-contact printer. The surrounding area between the printed biomolecules was passivated with polyethylene glycol-bisamine (A-PEG) to prevent non-specific cell attachment. EPCs were seeded onto the microarray platform and cell numbers quantified after 1 h (to determine capture) and 72 h (to determine proliferation). All of the extracellular matrix (ECM) biomolecules printed demonstrated an ability to capture EPCs within 1 h of cell seeding with Col II exhibiting the highest level of attachment when compared to the other biomolecules. Interestingly, Col IV exhibited the highest increase in EPC expansion after 72 h when compared to Col I, Col II and VEGF-A. These results provide information for significant improvement in the capture and expansion of human EPC for further application.

Keywords: biomolecules, cell microarray platform, cell therapy, endothelial progenitor cells, high throughput screening

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Authors: P. Weerkamp Bartholomeus

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Autism treatment evaluation is crucial for monitoring the development of an intervention at an early stage. ‘ReAttach’ is a new intervention based on the principles of attachment and social cognitive training. Practical research suggests promising results on a variety of developmental areas. Five years after the first ReAttach sessions these findings can be extended with qualitative research by means of follow-up interviews. The potential impact of this treatment on daily life functioning and well-being of autistic persons becomes clear.

Keywords: autism, innovation, treatment, social cognitive training

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Authors: Juariah Salam Suryadi

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North coast (Pantura) line is known as a high-risk area related to reproductive health. This is because along the line, there are many food stalls and entertainment industries that at night the function changed to be sexual transaction areas. This business line also facilitate circulation and transaction of drug and substance abuse. The environment conditions can influence adolescents who live in this area. It is because of adolescence characteristics that has high curiosity and looking for their identities. Therefore, purposes of this study were to explore reproductive health behaviour of early adolescents who lived in Pantura line and to suggest intervention based on the adolescents reproductive health conditions. This study was conducted in November 2016 among the seventh-grade students of Pusakajaya Junior High School 1 and 2, Subang District. Number of respondents were 269 students (Male=135, Female=134). The students were interviewed using a semi-structured questionnaire. Some teachers also interviewed to complement the data. The quantitative data was analyzed with univariate analysis, while content analysis was used for the qualitative data. Findings of this study showed that 85,2% of male students were smoker. Most of them started smoking at elementary school. Male students who often drunk alcohol were about 25,2% and all of them initiated to drink at elementary school. There were about 21,5% of male students ever used drug and substance abuse. There were 54,6% of the students that confessed having a lover. Most of them were female students. Sexual behaviour that ever done with their lovers were: holding hands (37,4%), kissing (4%) and embracing (6,8%). Although all of the students claimed to have never had sexual intercourse, but 5,9% of them said that they had friends who have had sexual intercourse. Most of the students also had friends with negative characteristics. Their friends were smoker (82,2%), drinker (53,2%) and drug abuse (42%). Most of the students recognized that they took the risks behaviour to get pleasure with their peers. Information from the teachers indicated that most problem of male students were smoking and drug and substance abuse; while sexuality including unwanted pregnancies were reproductive problems of many female students. Therefore, It is recommended to enhance understanding of the adolescents about risks of unhealthy behaviour through continuing reproductive health education, both in school and out of school. Policy support to create positive social environment and adolescents friendly is also suggested.

Keywords: reproductive health, behaviour, early adolescents, pantura line

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Authors: Michela Terlizzi, Chiara Colarusso, Aldo Pinto, Rosalinda Sorrentino

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Sphingosine-1-phosphate (S1P) is a membrane-derived bioactive phospholipid exerting a multitude of effects on respiratory cell physiology and pathology through five S1P receptors (S1PR1-5). Higher levels of S1P have been registered in a broad range of respiratory diseases, including inflammatory disorders and cancer, although its exact role is still elusive. Based on our previous study in which we found that S1P/S1PR3 is involved in an inflammatory pattern via the activation of Toll-like Receptor 9 (TLR9), highly expressed on lung cancer cells, the main goal of the current study was to better understand the involvement of S1P/S1PR3 pathway/signaling during lung carcinogenesis, taking advantage of a mouse model of first-hand smoke exposure and of carcinogen-induced lung cancer. We used human samples of Non-Small Cell Lung Cancer (NSCLC), a mouse model of first-hand smoking, and of Benzo(a)pyrene (BaP)-induced tumor-bearing mice and A549 lung adenocarcinoma cells. We found that the intranuclear, but not the membrane, localization of S1PR3 was associated to the proliferation of lung adenocarcinoma cells, the mechanism that was correlated to human and mouse samples of smoke-exposure and carcinogen-induced lung cancer, which were characterized by higher utilization of S1P. Indeed, the inhibition of the membrane S1PR3 did not alter tumor cell proliferation after TLR9 activation. Instead, according to the nuclear localization of sphingosine kinase (SPHK) II, the enzyme responsible for the catalysis of the S1P last step synthesis, the inhibition of the kinase completely blocked the endogenous S1P-induced tumor cell proliferation. These results prove that the endogenous TLR9-induced S1P can on one side favor pro-inflammatory mechanisms in the tumor microenvironment via the activation of cell surface receptors, but on the other tumor progression via the nuclear S1PR3/SPHK II axis, highlighting a novel molecular mechanism that identifies S1P as one of the crucial mediators for lung carcinogenesis-associated inflammatory processes and that could provide differential therapeutic approaches especially in non-responsive lung cancer patients.

Keywords: sphingosine-1-phosphate (S1P), S1P Receptor 3 (S1PR3), smoking-mice, lung inflammation, lung cancer

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