Search results for: interaction medicine

Authors: Rose Branch-Allen, John Jayachandran

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Background and purpose: Canada is a pluralistic, multicultural society with an ethno-cultural composition that has been shaped over time by immigrants and their descendants. Although Canada welcomes these immigrants, many will endure hardship and assimilation difficulties. Despite these life hurdles, surveys consistently disclose high life satisfaction for all Canadians. Most research studies on Life Satisfaction/ Subjective Wellbeing (SWB) have focused on one main determinant and a variety of social demographic variables to delineate the determinants of life satisfaction. However, very few research studies examine life satisfaction from a holistic approach. In addition, we need to understand the causal pathways leading to life satisfaction, and develop theories that explain why certain variables differentially influence the different components of SWB. The aim this study was to utilize a holistic approach to construct a causal model and identify major determinants of life satisfaction. Data and measures: This study utilized data from the General Social Survey, with a sample size of 19, 597. The exogenous concepts included age, gender, marital status, household size, socioeconomic status, ethnicity, location, immigration status, religiosity, and neighborhood. The intervening concepts included health, social contact, leisure, enjoyment, work-family balance, quality time, domestic labor, and sense of belonging. The endogenous concept life satisfaction was measured by multiple indicators (Cronbach’s alpha = .83). Analysis: Several multiple regression models were run sequentially to estimate path coefficients for the causal model. Results: Overall, above average satisfaction with life was reported for respondents with specific socio-economic, demographic and lifestyle characteristics. With regard to exogenous factors, respondents who were female, younger, married, from high socioeconomic status background, born in Canada, very religious, and demonstrated high level of neighborhood interaction had greater satisfaction with life. Similarly, intervening concepts suggested respondents had greater life satisfaction if they had better health, more social contact, less time on passive leisure activities and more time on active leisure activities, more time with family and friends, more enjoyment with volunteer activities, less time on domestic labor and a greater sense of belonging to the community. Conclusions and Implications: Our results suggest that a holistic approach is necessary for establishing determinants of life satisfaction, and that life satisfaction is not merely comprised of positive or negative affect rather understanding the causal process of life satisfaction. Even though, most of our findings are consistent with previous studies, a significant number of causal connections contradict some of the findings in literature today. We have provided possible explanation for these anomalies researchers encounter in studying life satisfaction and policy implications.

Keywords: causal model, holistic approach, life satisfaction, socio-demographic variables, subjective well-being

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Authors: Henry Nicholas Lee, George Thomas, Juliana Johari, Carmilla Freddie, Caroline Val Madin

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Research in comparative and international education often provides value-laden views of an education system within and in between other countries. These views are frequently used by policy makers or educators to explore similarities and differences for, among others, benchmarking purposes. In this study, a comparison is made between Malaysia and England, focusing on the process of writing children went through to create a text, using a multimodal theoretical framework to analyse this comparison. The main purpose is political in nature as it served as an answer to Malaysia’s call for benchmarking of best practices for language learning. Furthermore, the focus on writing in this study adds into more empirical findings about early writers’ writing development and writing improvement, especially for children at the ages of 5-9. In research, comparative studies in English as a Second Language (ESL) writing pedagogy – particularly in Malaysia since the introduction of the Standard- based English Language Curriculum (KSSR) in 2011 as a draft and its full implementation in 2017; reviewed 2018 KSSR-CEFR aligned – has not been done comparatively. In theory, a multimodal theoretical framework somehow allows a logical comparison between first language and ESL which would provide useful insights to illuminate the writing process between Malaysia and England. The comparisons are not representative because of the different school systems in both countries. So far, the literature informs us that the curriculum for language learning is very much emphasised on children’s linguistic abilities, which include their proficiency and mastery of the language, its conventions, and technicalities. However, recent empirical findings suggested that literacy in its concepts and characters need change. In view of this suggestion, the comparison will look at how the process of writing is implemented through the five modes of communication: linguistic, visual, aural, spatial, and gestural. This project draws on data from Malaysia and England, involving 10 teachers, 26 classroom observations, 20 lesson plans, 20 interviews, and 20 brief conversations with teachers. The research focused upon 20 primary children of different genders aged 5-9, and in addition to primary data descriptions, 40 children’s works, 40 brief classroom conversations, 30 classroom photographs, and 30 school compound photographs were undertaken to investigate teachers and children’s use of modes and semiotic resources to design a text. The data were analysed by means of within-case analysis, cross-case analysis, and constant comparative analysis, with an initial stage of data categorisation, followed by general and specific coding, which clustered the data into thematic groups. The study highlights the importance of teachers’ and children’s engagement and interaction with various modes of communication, an adaptation from the English approaches to teaching writing within the KSSR framework and providing ‘voice’ to ESL writers to ensure that both have access to the knowledge and skills required to make decisions in developing multimodal texts and artefacts.

Keywords: comparative education, early writers, KSSR, multimodal theoretical framework, writing development

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Authors: Wei Xiao, Gangzhi Cai, Xingliang Qin, Hongyan Ren, Zaidong Hua, Zhe Zhu, Hongwei Xiao, Ximin Zheng, Jie Yao, Yanzhen Bi

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Myostatin (MSTN) is the master regulator of double muscling phenotype with overgrown muscle and decreased fatness in animals, but its action mode to regulate fat deposition remains to be elucidated. In this study a swin-specific pathway through which MSTN acts to regulate the fat deposition was deciphered. Deep sequenincing of the mRNA and miRNA of fat tissues of MSTN knockout (KO) and wildtype (WT) pigs discovered the positive correlation of myocyte enhancer factor 2C (MEF2C) and fat-inhibiting miR222 expression, and the inverse correlation of miR222 and stearoyl-CoA desaturase 5 (SCD5) expression. SCD5 is rodent-absent and expressed only in pig, sheep and cattle. Fatty acid spectrum of fat tissues revealed a lower percentage of oleoyl-CoA (18:1) and palmitoleyl CoA (16:1) in MSTN KO pigs, which are the catalyzing products of SCD5-mediated desaturation of steroyl CoA (18:0) and palmitoyl CoA (16:0). Blood metrics demonstrated a 45% decline of triglyceride (TG) content in MSTN KO pigs. In light of these observations we hypothesized that MSTN might act through MEF2C/miR222/SCD5 pathway to regulate desaturation of fatty acid as well as triglyceride synthesis in pigs. To this end, real-time PCR and Western blotting were carried out to detect the expression of the three genes stated above. These experiments showed that MEF2C expression was up-regulated by nearly 2-fold, miR222 up-regulated by nearly 3-fold and SCD5 down-regulated by nearly 50% in MSTN KO pigs. These data were consistent with the expression change in deep sequencing analysis. Dual luciferase reporter was then used to confirm the regulation of MEF2C upon the promoter of miR222. Ecotopic expression of MEF2C in preadipocyte cells enhanced miR222 expression by 3.48-fold. CHIP-PCR identified a putative binding site of MEF2C on -2077 to -2066 region of miR222 promoter. Electrophoretic mobility shift assay (EMSA) demonstrated the interaction of MEF2C and miR222 promoter in vitro. These data indicated that MEF2C transcriptionally regulates the expression of miR222. Next, the regulation of miR222 on SCD5 mRNA as well as its physiological consequences were examined. Dual luciferase reporter testing revealed the translational inhibition of miR222 upon the 3´ UTR (untranslated region) of SCD5 in preadipocyte cells. Transfection of miR222 mimics and inhibitors resulted in the down-regulation and up-regulation of SCD5 in preadipocyte cells respectively, consistent with the results from reporter testing. RNA interference of SCD5 in preadipocyte cells caused 26.2% reduction of TG, in agreement with the results of TG content in MSTN KO pigs. In summary, the results above supported the existence of a molecular pathway that MSTN signals through MEF2C/miR222/SCD5 to regulate the fat deposition in pigs. This swine-specific pathway offers potential molecular markers for the development and breeding of a new pig line with optimised fatty acid composition. This would benefit human health by decreasing the takeup of saturated fatty acid.

Keywords: fat deposition, MEF2C, miR222, myostatin, SCD5, pig

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Authors: Anna Demian, Levi Howard, L. Ng, Leslie Simon, Mark Dragon, A. Desai, Timothy Devlantes, W. David Freeman

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Introduction: Out-of-hospital cardiac arrest (OHCA) can carry a high mortality. For survivors, the most common complication is hypoxic-ischemic brain injury (HIBI). Rarely, lumbosacral spinal cord and/or other spinal cord artery ischemia can occur due to anatomic variation and variable mean arterial pressure after the return of spontaneous circulation. We present a case of an OHCA survivor who later woke up with bilateral leg weakness with preserved sensation (ASIA grade B, L2 level). Methods: We describe a clinical, radiographic, and laboratory presentation, as well as a National Library of Medicine (NLM) search engine methodology, characterizing incidence/prevalence of this entity is discussed. A 70-year-old male, a longtime smoker, and alcohol user, suddenly collapsed at a bar surrounded by friends. He had complained of chest pain before collapsing. 911 was called. EMS arrived, and the patient was in pulseless electrical activity (PEA), cardiopulmonary resuscitation (CPR) was initiated, and the patient was intubated, and a LUCAS device was applied for continuous, high-quality CPR in the field by EMS. In the ED, central lines were placed, and thrombolysis was administered for a suspected Pulmonary Embolism (PE). It was a prolonged code that lasted 90 minutes. The code continued with the eventual return of spontaneous circulation. The patient was placed on an epinephrine and norepinephrine drip to maintain blood pressure. ECHO was performed and showed a “D-shaped” ventricle worrisome for PE as well as an ejection fraction around 30%. A CT with PE protocol was performed and confirmed bilateral PE. Results: The patient woke up 24 hours later, following commands, and was extubated. He was found paraplegic below L2 with preserved sensation, with hypotonia and areflexia consistent with “spinal shock” or anterior spinal cord syndrome. MRI thoracic and lumbar spine showed a conus medullaris level spinal cord infarction. The patient was given IV steroids upon initial discovery of cord infarct. NLM search using “cardiac arrest” and “spinal cord infarction” revealed 57 results, with only 8 review articles. Risk factors include age, atherosclerotic disease, and intraaortic balloon pump placement. AoA (Artery of Adamkiewicz) anatomic variation along with existing atherosclerotic factors and low perfusion were also known risk factors. Conclusion: Acute paraplegia from anterior spinal cord infarction of the AoA territory after cardiac arrest is rare. Larger prospective, multicenter trials are needed to examine potential interventions of hypothermia, lumbar drains, which are sometimes used in aortic surgery to reduce ischemia and/or other neuroprotectants.

Keywords: cardiac arrest, spinal cord infarction, artery of Adamkiewicz, paraplegia

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Authors: Stephen Bahooshy

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Our understanding of gender inequality has advanced in recent years. Differences in pay and societal gendered behaviour expectations have been emphasized. It is acknowledged globally that gender shapes everyone’s experiences of health and social care, including access to care, use of services and products, and the interaction with care providers. NHS Digital in England collects data from local authorities on the number of carers and people with support needs and the services they access. This data does not provide a gender breakdown. Caring can have many positive and negative impacts on carers’ health and wellbeing. For example, caring can improve physical health, provide a sense of pride and purpose, and reduced stress levels for those who undertake a caring role by choice. Negatives of caring include financial concerns, social isolation, a reduction in earnings, and not being recognized as a carer or involved and consulted by health and social care professionals. Treating male and female carers differently is by definition unequitable and precludes one gender from receiving the benefits of caring whilst potentially overburdening the other with the negatives of caring. In order to explore the issue on a preliminary basis, five local authorities who provide statutory adult social care services in England were sent Freedom of Information requests in 2019. The authorities were selected to include county councils and London boroughs. The authorities were asked to provide data on the amount of money spent on care at home packages to people over 65 years, broken down by gender and carer gender for each financial year between 2013 and 2019. Results indicated that in each financial year, female carers supporting someone over 65 years received less financial support for care at home support packages than male carers. Over the six-year period, this difference equated to a £9.5k deficit in financial support received on average per female carer when compared to male carers. An example of a London borough with the highest disparity presented an average weekly spend on care at home for people over 65 with a carer of £261.35 for male carers and £165.46 for female carers. Consequently, female carers in this borough received on average £95.89 less per week in care at home support than male carers. This highlights a real and potentially detrimental disparity in the care support received to female carers in order to support them to continue to care in parts of England. More research should be undertaken in this area to better explore this issue and to understand if these findings are unique to these social care providers or part of a wider phenomenon. NHS Digital should request local authorities collect data on gender in the same way that large employers in the United Kingdom are required by law to provide data on staff salaries by gender. People who allocate social care packages of support should consider the impact of gender when allocating support packages to people with support needs and who have carers to reduce any potential impact of gender bias on their decision-making.

Keywords: caregivers, carers, gender equality, social care

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Authors: Alua Massalimova

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Situation analysis of Blood Service revealed that the strengths dominated over the weak 1.4 times. The possibilities dominate over the threats by 1.1 times. It follows that by using timely the possibility the Service, it is possible to strengthen its strengths and avoid threats. Priority directions of the resulting analysis are the use of subjective factors, such as personal management capacity managers of the Blood Center in the field of possibilities of legal activity of administrative decisions and the mobilization of stable staff in general market conditions. We have studied for the period 2011-2015 retrospectively indicators of Blood Service of Kazakhstan. Strengths of Blood Service of RK(Ps4,5): 1) indicators of donations for 1000 people is higher than in some countries of the CIS (in Russia 14, Kazakhstan - 17); 2) the functioning science centre of transfusiology; 3) the legal possibility of additional financing blood centers in the form of paid services; 4) the absence of competitors; 5) training on specialty Transfusiology; 6) the stable management staff of blood centers, a high level of competence; 7) increase in the incidence requiring transfusion therapy (oncohematology); 8) equipment upgrades; 9) the opening of a reference laboratory; 10) growth of the proportion of issued high-quality blood components; 11) governmental organization 'Drop of Life'; 12) the functioning bone marrow register; 13) equipped with modern equipment HLA-laboratory; 14) High categorization of average medical workers; 15) availability of own specialized scientific journal; 16) vivarium. The weaknesses (Ps = 3.5): 1) the incomplete equipping of blood centers and blood transfusion cabinets according to standards; 2) low specific weight of paid services of the CC; 3) low categorization of doctors; 4) high staff turnover; 5) the low scientific potential of industrial and clinical of transfusiology; 6) the low wages paid; 7) slight growth of harvested donor blood; 8) the weak continuity with offices blood transfusion; 9) lack of agitation work; 10) the formally functioning of Transfusion Association; 11) the absence of scientific laboratories; 12) high standard deviation from the average for donations in the republic. The possibilities (Ps = 2,7): 1): international grants; 2) organization of international seminars on clinical of transfusiology; 3) cross-sectoral cooperation; 4) to increase scientific research in the field of clinical of transfusiology; 5) reduce the share of donation unsuitable for transfusion and processing; 6) strengthening marketing management in the development of fee-based services; 7) advertising paid services; 8) strengthening the publishing of teaching aids; 9) team-building staff. The threats (Ps = 2.1): 1) an increase of staff turnover; 2) the risk of litigation; 3) reduction gemoprodukts based on evidence-based medicine; 4) regression of scientific capacity; 5) organization of marketing; 6) transfusiologist marketing; 7) reduction in the quality of the evidence base transfusions.

Keywords: blood service, healthcare, Kazakhstan, quantative swot analysis

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Authors: D. Bikiaris, M. Nerantzaki, I. Koliakou, A. Francone, N. Kehagias

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In the present study, the formation of structures in poly(lactic acid) (PLA) has been investigated with respect to producing areas of regular, superficial features with dimensions comparable to those of cells or biological macromolecules. Nanoimprint lithography, a method of pattern replication in polymers, has been used for the production of features ranging from tens of micrometers, covering areas up to 1 cm², down to hundreds of nanometers. Both micro- and nano-structures were faithfully replicated. Potentially, PLA has wide uses within biomedical fields, from implantable medical devices, including screws and pins, to membrane applications, such as wound covers, and even as an injectable polymer for, for example, lipoatrophy. The possibility of fabricating structured PLA surfaces, with structures of the dimensions associated with cells or biological macro- molecules, is of interest in fields such as cellular engineering. Imprint-based technologies have demonstrated the ability to selectively imprint polymer films over large areas resulting in 3D imprints over flat, curved or pre-patterned surfaces. Here, we compare nano-patterned with nano-patterned by nanoimprint lithography (NIL) PLA film. A silicon nanostructured stamp (provided by Nanotypos company) having positive and negative protrusions was used to pattern PLA films by means of thermal NIL. The polymer film was heated from 40°C to 60°C above its Tg and embossed with a pressure of 60 bars for 3 min. The stamp and substrate were demolded at room temperature. Scanning electron microscope (SEM) images showed good replication fidelity of the replicated Si stamp. Contact-angle measurements suggested that positive microstructuring of the polymer (where features protrude from the polymer surface) produced a more hydrophilic surface than negative micro-structuring. The ability to structure the surface of the poly(lactic acid), allied to the polymer’s post-processing transparency and proven biocompatibility. Films produced in this were also shown to enhance the aligned attachment behavior and proliferation of Wharton’s Jelly Mesenchymal Stem cells, leading to the observed growth contact guidance. The bacterial attachment patterns of some bacteria, highlighted that the nano-patterned PLA structure can reduce the propensity for the bacteria to attach to the surface, with a greater bactericidal being demonstrated activity against the Staphylococcus aureus cells. These biocompatible, micro- and nanopatterned PLA surfaces could be useful for polymer– cell interaction experiments at dimensions at, or below, that of individual cells. Indeed, post-fabrication modification of the microstructured PLA surface, with materials such as collagen (which can further reduce the hydrophobicity of the surface), will extend the range of applications, possibly through the use of PLA’s inherent biodegradability. Further study is being undertaken to examine whether these structures promote cell growth on the polymer surface.

Keywords: poly(lactic acid), nano-imprint lithography, anti-bacterial properties, PLA

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Authors: J. Lino Alves, L. Lopes

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It is not new that industrial design projects are a result of cooperative work from different areas of knowledge. However, in the academic teaching of Industrial Design and Mechanical Engineering courses, it is not recurrent that those competences are mixed before the professional life arrives. This abstract intends to describe two semester experiences carried out by two professors - a mechanical engineer and an industrial designer - in the last two academic years, for which they created mixed teams of Industrial Design and Mechanical Engineering (UPorto University). The two experiences differ in several factors; the main one is related to the challenges of online education, a constraint that affected the second experience. In the first year, even before foreseeing the effects that the pandemic would reconfigure the education system, a partnership with the Education Service of Águas do Porto was established. The purpose of the exercise was the project development of a game that could be an interaction element oriented to potentiate a positive experience and as an educational contribution to the children. In the second year, already foreseeing that the teaching experience would be carried out online, it was decided to design an open briefing, which allowed the groups to choose among three themes: a hand scale game using additive manufacturing; a modular system for ventilated facade using a parametric design basis; or, a modular system for vertical gardens. In methodological terms, besides the weekly follow-up, with the simultaneous support of the two professors, a group self-evaluation was requested; and a form to be filled individually to evaluate other groups. One of the first conclusions is related to the briefing format. Industrial Design students seem comfortable working on an open briefing that allows them to draw the project on a conceptual basis created for that purpose; on the other hand, Mechanical Engineering students were uncomfortable and insecure in the initial phase due to the absence of concrete, closed "order." In other words, it is not recurrent for Mechanical Engineering students that the creative component is stimulated, seemingly leaving them reserved to the technical solution and execution, depriving them of the co-creation phase during the conceptual construction of the project's own brief. Another fact that was registered is related to the leadership positions in the groups, which alternated according to the state of development of the project: design students took the lead during the ideation/concept phase, while mechanical engineering ones took a greater lead during the intermediate development process, namely in the definition of constructive solutions, mass/volume calculations, manufacturing, and material resistance. Designers' competences were again more evident and assumed in the final phase, especially in communication skills, as well as in simulations in the context of use. However, at some moments, it was visible the capacity for quite balanced leadership between engineering and design, in a constant debate centered on the human factor of the project - evidenced in the final solution, in the compromise and balance between technical constraints, functionality, usability, and aesthetics.

Keywords: education, industrial design, mechanical engineering, teaching ethodologies

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Authors: Lia Marchi, Ernesto Antonini

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The impact of industrial sites on people’s living environment both involves detrimental effects on the ecosystem and perceptual-aesthetic interferences with the scenery. These, in turn, affect the economic and social value of the landscape, as well as the wellbeing of workers and local communities. Given the diffusion of the phenomenon and the relevance of its effects, it emerges the need for a joint approach to assess and thus mitigate the impact of factories on the landscape –being this latest assumed as the result of the action and interaction of natural and human factors. However, the impact assessment tools suitable for the purpose are quite heterogeneous and mostly monodisciplinary. On the one hand, green building rating systems (GBRSs) are increasingly used to evaluate the performance of manufacturing sites, mainly by quantitative indicators focused on environmental issues. On the other hand, methods to detect the visual and social impact of factories on the landscape are gradually emerging in the literature, but they generally adopt only qualitative gauges. The research addresses the integration of the environmental impact assessment and the perceptual-aesthetic interferences of factories on the landscape. The GBRSs model is assumed as a reference since it is adequate to simultaneously investigate different topics which affect sustainability, returning a global score. A critical analysis of GBRSs relevant to industrial facilities has led to select the U.S. GBC LEED protocol as the most suitable to the scope. A revision of LEED v4 Building Design+Construction has then been provided by including specific indicators to measure the interferences of manufacturing sites with the perceptual-aesthetic and social aspects of the territory. To this end, a new impact category was defined, namely ‘PA - Perceptual-aesthetic aspects’, comprising eight new credits which are specifically designed to assess how much the buildings are in harmony with their surroundings: these investigate, for example the morphological and chromatic harmonization of the facility with the scenery or the site receptiveness and attractiveness. The credits weighting table was consequently revised, according to the LEED points allocation system. As all LEED credits, each new PA credit is thoroughly described in a sheet setting its aim, requirements, and the available options to gauge the interference and get a score. Lastly, each credit is related to mitigation tactics, which are drawn from a catalogue of exemplary case studies, it also developed by the research. The result is a modified LEED scheme which includes compatibility with the landscape within the sustainability assessment of the industrial sites. The whole system consists of 10 evaluation categories, which contain in total 62 credits. Lastly, a test of the tool on an Italian factory was performed, allowing the comparison of three mitigation scenarios with increasing compatibility level. The study proposes a holistic and viable approach to the environmental impact assessment of factories by a tool which integrates the multiple involved aspects within a worldwide recognized rating protocol.

Keywords: environmental impact, GBRS, landscape, LEED, sustainable factory

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Authors: Chen Wang, Gerard Rowe

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The number of undergraduate engineering students enrolled in university has been increasing rapidly recently, leading to challenges associated with increased student-instructor ratios and increased diversity in academic preparedness of the entrants. An increased student-instructor ratio makes the interaction between teachers and students more difficult, with the resulting student ‘anonymity’ known to be a risk to academic success. With increasing student numbers, there is also an increasing diversity in the academic preparedness of the students at entry to university. Conceptual understanding of the entrants has been quantified via diagnostic testing, with the results for the first-year course in electrical engineering showing significant conceptual misunderstandings amongst the entry cohort. The solution is clearly multi-faceted, but part of the solution likely involves greater demands being placed on students to be masters of their own learning. In consequence, it is highly desirable that instructors help students to develop better self-regulated learning skills. A self-regulated learner is one who is capable of setting up their own learning goals, monitoring their study processes, adopting and adjusting learning strategies, and reflecting on their own study achievements. The methods by which instructors might cultivate students’ self-regulated learning abilities is receiving increasing attention from instructors and researchers. The aim of this study was to help students understand fully their self-regulated learning skill levels and provide targeted instructions to help them improve particular learning abilities in order to meet the curriculum requirements. As a survey tool, this research applied the questionnaire ‘Motivated Strategies for Learning Questionnaire’ (MSLQ) to collect first year engineering student’s self-reported data of their cognitive abilities, motivational orientations and learning strategies. MSLQ is a widely-used questionnaire for assessment of university student’s self-regulated learning skills. The questionnaire was offered online as a part of the online-scaffolding-learning tools to develop student understanding of self-regulated learning theories and learning strategies. The online tools, which have been under development since 2015, are designed to help first-year students understand their self-regulated learning skill levels by providing prompt feedback after they complete the questionnaire. In addition, the online tool also supplies corresponding learning strategies to students if they want to improve specific learning skills. A total of 866 first year engineering students who enrolled in the first-year electrical engineering course were invited to participate in this research project. By the end of the course 857 students responded and 738 of their questionnaires were considered as valid questionnaires. Analysis of these surveys showed that 66% of the students thought the online-scaffolding-learning tools helped significantly to improve their self-regulated learning abilities. It was particularly pleasing that 16.4% of the respondents thought the online-scaffolding-learning tools were extremely effective. A current thrust of our research is to investigate the relationships between students’ self-regulated learning abilities and their academic performance. Our results are being used by the course instructors as they revise the curriculum and pedagogy for this fundamental first-year engineering course, but the general principles we have identified are applicable to most first-year STEM courses.

Keywords: academic preparedness, online-scaffolding-learning tool, self-regulated learning, STEM education

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Authors: Orkide Donma, Mustafa M. Donma

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Childhood obesity, which may lead to increased risk for heart diseases in children as well as adults, is one of the most important health problems throughout the world. Prevalences of morbid obesity and metabolic syndrome (MetS) are being increased during childhood age group. MetS is a cluster of metabolic and vascular abnormalities including hypercoagulability and an increased risk of cardiovascular diseases (CVDs). There are also some relations between some components of MetS and leukocytes. The aim of this study is to investigate complete blood cell count parameters that differ between morbidly obese boys and girls with MetS diagnosis. A total of 117 morbid obese children with MetS consulted to Department of Pediatrics in Faculty of Medicine Hospital at Namik Kemal University were included into the scope of the study. The study population was classified based upon their genders (60 girls and 57 boys). Their heights and weights were measured and body mass index (BMI) values were calculated. WHO BMI-for age and sex percentiles were used. The values above 99 percentile were defined as morbid obesity. Anthropometric measurements were performed. Waist-to-hip and head-to-neck ratios as well as homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. Components of MetS (central obesity, glucose intolerance, high blood pressure, high triacylglycerol levels, low levels of high density lipoprotein cholesterol) were determined. Hematological variables were measured. Statistical analyses were performed using SPSS. The degree for statistical significance was p ≤ 0.05. There was no statistically significant difference between the ages (11.2±2.6 years vs 11.2±3.0 years) and BMIs (28.6±5.2 kg/m² vs 29.3±5.2 kg/m²) of boys and girls (p ≥ 0.05), respectively. Significantly increased waist-to-hip ratios were obtained for boys (0.94±0.08 vs 0.91±0.06; p=0.023). Significantly elevated values of hemoglobin (13.55±0.98 vs 13.06±0.82; p=0.004), mean corpuscular hemoglobin concentration (33.79±0.91 vs 33.21±1.14; p=0.003), eosinophils (0.300±0.253 vs 0.196±0.197; p=0.014), and platelet (347.1±81.7 vs 319.0±65.9; p=0.042) were detected for boys. There was no statistically significant difference between the groups in terms of neutrophil/lymphocyte ratios as well as HOMA-IR values (p ≥ 0.05). Statistically significant gender-based differences were found for hemoglobin as well as mean corpuscular hemoglobin concentration and hence, separate reference intervals for two genders should be considered for these parameters. Eosinophils may contribute to the development of thrombus in acute coronary syndrome. Eosinophils are also known to make an important contribution to mechanisms related to thrombosis pathogenesis in acute myocardial infarction. Increased platelet activity is observed in patients with MetS and these individuals are more susceptible to CVDs. In our study, elevated platelets described as dominant contributors to hypercoagulability and elevated eosinophil counts suggested to be related to the development of CVDs observed in boys may be the early indicators of the future cardiometabolic complications in this gender.

Keywords: children, complete blood count, gender, metabolic syndrome

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Authors: Kelly Jaunzems

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Social media is a powerful instrument of communication, enabling the presentation of information in multiple forms and modes, amplifying the interactions between people, organisations, and stakeholders, and increasing the range of communication channels available. Younger generations are highly engaged with social media and more likely to use this channel than any other to seek information. Given this, it may appear extraordinary that occupational safety and health professionals have yet to seriously engage with social media for communicating safety messages to younger audiences who, in many industries, might be statistically more likely to encounter more workplace harm or injury. Millennials, defined as those born between 1981-2000, have distinctive characteristics that also impact their interaction patterns rendering many traditional occupational safety and health communication channels sub-optimal or near obsolete. Used to immediate responses, 280-character communication, shares, likes, and visual imagery, millennials struggle to take seriously the low-tech, top-down communication channels such as safety noticeboards, toolbox meetings, and passive tick-box online inductions favoured by traditional OSH professionals. This paper draws upon well-established communication findings, which argue that it is important to know a target audience and reach them using their preferred communication pathways, particularly if the aim is to impact attitudes and behaviours. Health practitioners have adopted social media as a communication channel with great success, yet safety practitioners have failed to follow this lead. Using a digital ethnography approach, this paper examines seven organisations’ Facebook posts from two one-month periods one year apart, one in 2018 and one in 2019. Each of the years informs organisation-based case studies. Comparing, contrasting, and drawing upon these case studies, the paper discusses and evaluates the (non) use of social media communication of safety information in terms of user engagement, shareability, and overall appeal. The success of health practitioners’ use of social media provides a compelling template for the implementation of social media into organisations’ safety communication strategies. Highly visible content such as that found on social media allows an organization to become more responsive and engage in two-way conversations with their audience, creating more engaged and participatory conversations around safety. Further, using social media to address younger audiences with a range of tonal qualities (for example, the use of humour) can achieve cut through in a way that grim statistics fail to do. On the basis of 18 months of interviews, filed work, and data analysis, the paper concludes with recommendations for communicating safety information via social media. It proposes exploration of the social media communication formula that, when utilised by safety practitioners, may create an effective social media presence. It is anticipated that such social media use will increase engagement, expand the number of followers and reduce the likelihood and severity of safety-related incidents. The tools offered may provide a path for safety practitioners to reach a disengaged generation of workers to build a cohesive and inclusive conversation around ways to keep people safe at work.

Keywords: social media, workplace safety, communication strategies, young workers

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Authors: Samuele Viaro, Pierre Ricco

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Görtler instabilities generate in boundary layers from an unbalance between pressure and centrifugal forces caused by concave surfaces. Their spatial streamwise evolution influences transition to turbulence. It is therefore important to understand even the early stages where perturbations, still small, grow linearly and could be controlled more easily. This work presents a rigorous theoretical framework for compressible flows using the linearized unsteady boundary region equations, where only the streamwise pressure gradient and streamwise diffusion terms are neglected from the full governing equations of fluid motion. Boundary and initial conditions are imposed through an asymptotic analysis in order to account for the interaction of the boundary layer with free-stream turbulence. The resulting parabolic system is discretize with a second-order finite difference scheme. Realistic flow parameters are chosen from wind tunnel studies performed at supersonic and subsonic conditions. The Mach number ranges from 0.5 to 8, with two different radii of curvature, 5 m and 10 m, frequencies up to 2000 Hz, and vortex spanwise wavelengths from 5 mm to 20 mm. The evolution of the perturbation flow is shown through velocity, temperature, pressure profiles relatively close to the leading edge, where non-linear effects can still be neglected, and growth rate. Results show that a global stabilizing effect exists with the increase of Mach number, frequency, spanwise wavenumber and radius of curvature. In particular, at high Mach numbers curvature effects are less pronounced and thermal streaks become stronger than velocity streaks. This increase of temperature perturbations saturates at approximately Mach 4 flows, and is limited in the early stage of growth, near the leading edge. In general, Görtler vortices evolve closer to the surface with respect to a flat plate scenario but their location shifts toward the edge of the boundary layer as the Mach number increases. In fact, a jet-like behavior appears for steady vortices having small spanwise wavelengths (less than 10 mm) at Mach 8, creating a region of unperturbed flow close to the wall. A similar response is also found at the highest frequency considered for a Mach 3 flow. Larger vortices are found to have a higher growth rate but are less influenced by the Mach number. An eigenvalue approach is also employed to study the amplification of the perturbations sufficiently downstream from the leading edge. These eigenvalue results are compared with the ones obtained through the initial value approach with inhomogeneous free-stream boundary conditions. All of the parameters here studied have a significant influence on the evolution of the instabilities for the Görtler problem which is indeed highly dependent on initial conditions.

Keywords: compressible boundary layers, Görtler instabilities, receptivity, turbulence transition

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Authors: Eglal Y. Ali, Smita Rao, Anat Lubetzky, Wen Ling

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Background: Postural abnormalities, rigidity, clumsiness, and frequent falls are common among children with autism spectrum disorders (ASD). The central nervous system’s ability to process all reliable sensory inputs (weighting) and disregard potentially perturbing sensory input (reweighting) is critical for successfully maintaining standing postural control. This study examined how sensory inputs (visual and somatosensory) are weighted and reweighted to maintain standing postural control in children with ASD compared with typically developing (TD) children. Subjects: Forty (20 (TD) and 20 ASD) children and adolescents participated in this study. The groups were matched for age, weight, and height. Participants had normal somatosensory (no somatosensory hypersensitivity), visual, and vestibular perception. Participants with ASD were categorized with severity level 1 according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) and Social Responsiveness Scale. Methods: Using one force platform, the center of pressure (COP) was measured during quiet standing for 30 seconds, 3 times first standing on stable surface with eyes open (Condition 1), followed by randomization of the following 3 conditions: Condition 2 standing on stable surface with eyes closed, (visual input perturbed); Condition 3 standing on compliant foam surface with eyes open, (somatosensory input perturbed); and Condition 4 standing on compliant foam surface with eyes closed, (both visual and somatosensory inputs perturbed). Standing postural control was measured by three outcome measures: COP sway area, COP anterior-posterior (AP), and mediolateral (ML) path length (PL). A repeated measure mixed model Analysis of Variance was conducted to determine whether there was a significant difference between the two groups in the mean of the three outcome measures across the four conditions. Results: According to all three outcome measures, both groups showed a gradual increase in postural sway from condition 1 to condition 4. However, TD participants showed a larger postural sway than those with ASD. There was a significant main effect of condition on three outcome measures (p< 0.05). Only the COP AP PL showed a significant main effect of the group (p<0.05) and a significant group by condition interaction (p<0.05). In COP AP PL, TD participants showed a significant difference between condition 2 and the baseline (p<0.05), whereas the ASD group did not. This suggests that the ASD group did not weight visual input as much as the TD group. A significant difference between conditions for the ASD group was seen only when participants stood on foam regardless of the visual condition, suggesting that the ASD group relied more on the somatosensory inputs to maintain the standing postural control. Furthermore, the ASD group exhibited significantly smaller postural sway compared with TD participants during standing on the stable surface, whereas the postural sway of the ASD group was close to that of the TD group on foam. Conclusion: These results suggest that participants with high functioning ASD (level 1, no somatosensory hypersensitivity in ankles and feet) over-rely on somatosensory inputs and use a stiffening strategy for standing postural control. This deviation in the reweighting mechanism might explain the postural abnormalities mentioned above among children with ASD.

Keywords: autism spectrum disorders, postural sway, sensory weighting and reweighting, standing postural control

Procedia PDF Downloads 39

Authors: Eglal Y. Ali, Smita Rao, Anat Lubetzky, Wen Ling

Abstract:

Background: Postural abnormalities, rigidity, clumsiness, and frequent falls are common among children with autism spectrum disorders (ASD). The central nervous system’s ability to process all reliable sensory inputs (weighting) and disregard potentially perturbing sensory input (reweighting) is critical for successfully maintaining standing postural control. This study examined how sensory inputs (visual and somatosensory) are weighted and reweighted to maintain standing postural control in children with ASD compared with typically developing (TD) children. Subjects: Forty (20 (TD) and 20 ASD) children and adolescents participated in this study. The groups were matched for age, weight, and height. Participants had normal somatosensory (no somatosensory hypersensitivity), visual, and vestibular perception. Participants with ASD were categorized with severity level 1 according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) and Social Responsiveness Scale. Methods: Using one force platform, the center of pressure (COP) was measured during quiet standing for 30 seconds, 3 times first standing on stable surface with eyes open (Condition 1), followed by randomization of the following 3 conditions: Condition 2 standing on stable surface with eyes closed, (visual input perturbed); Condition 3 standing on a compliant foam surface with eyes open, (somatosensory input perturbed); and Condition 4 standing on a compliant foam surface with eyes closed, (both visual and somatosensory inputs perturbed). Standing postural control was measured by three outcome measures: COP sway area, COP anterior-posterior (AP), and mediolateral (ML) path length (PL). A repeated measure mixed model analysis of variance was conducted to determine whether there was a significant difference between the two groups in the mean of the three outcome measures across the four conditions. Results: According to all three outcome measures, both groups showed a gradual increase in postural sway from condition 1 to condition 4. However, TD participants showed a larger postural sway than those with ASD. There was a significant main effect of the condition on three outcome measures (p< 0.05). Only the COP AP PL showed a significant main effect of the group (p<0.05) and a significant group by condition interaction (p<0.05). In COP AP PL, TD participants showed a significant difference between condition 2 and the baseline (p<0.05), whereas the ASD group did not. This suggests that the ASD group did not weigh visual input as much as the TD group. A significant difference between conditions for the ASD group was seen only when participants stood on foam regardless of the visual condition, suggesting that the ASD group relied more on the somatosensory inputs to maintain the standing postural control. Furthermore, the ASD group exhibited significantly smaller postural sway compared with TD participants during standing on a stable surface, whereas the postural sway of the ASD group was close to that of the TD group on foam. Conclusion: These results suggest that participants with high-functioning ASD (level 1, no somatosensory hypersensitivity in ankles and feet) over-rely on somatosensory inputs and use a stiffening strategy for standing postural control. This deviation in the reweighting mechanism might explain the postural abnormalities mentioned above among children with ASD.

Keywords: autism spectrum disorders, postural sway, sensory weighting and reweighting, standing postural control

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Authors: Anthony S. Machi, Joseph Minardi

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We present a case report of left atrial myxoma diagnosed by bedside transesophageal (TEE) ultrasound. Left atrial myxoma is the most common benign cardiac tumor and can obstruct blood flow and cause valvular insufficiency. Common symptoms consist of dyspnea, pulmonary edema and other features of left heart failure in addition to thrombus release in the form of tumor fragments. The availability of bedside ultrasound equipment is essential for the quick diagnosis and treatment of various emergency conditions including cardiac neoplasms. A 48-year-old Caucasian female with a four-year history of an untreated renal mass and anemia presented to the ED with two months of sharp, intermittent, bilateral flank pain radiating into the abdomen. She also reported intermittent vomiting and constipation along with generalized body aches, night sweats, and 100-pound weight loss over last year. She had a CT in 2013 showing a 3 cm left renal mass and a second CT in April 2016 showing a 3.8 cm left renal mass along with a past medical history of diverticulosis, chronic bronchitis, dyspnea on exertion, uncontrolled hypertension, and hyperlipidemia. Her maternal family history is positive for breast cancer, hypertension, and Type II Diabetes. Her paternal family history is positive for stroke. She was a current everyday smoker with an 11 pack/year history. Alcohol and drug use were denied. Physical exam was notable for a Grade II/IV systolic murmur at the right upper sternal border, dyspnea on exertion without angina, and a tender left lower quadrant. Her vitals and labs were notable for a blood pressure of 144/96, heart rate of 96 beats per minute, pulse oximetry of 96%, hemoglobin of 7.6 g/dL, hypokalemia, hypochloremia, and multiple other abnormalities. Physicians ordered a CT to evaluate her flank pain which revealed a 7.2 x 8.9 x 10.5 cm mixed cystic/solid mass in the lower pole of the left kidney and a filling defect in the left atrium. Bedside TEE was ordered to follow up on the filling defect. TEE reported an ejection fraction of 60-65% and visualized a mobile 6 x 3 cm mass in the left atrium attached to the interatrial septum extending into the mitral valve. Cardiothoracic Surgery and Urology were consulted and confirmed a diagnosis of left atrial myxoma and clear cell renal cell carcinoma. The patient returned a week later due to worsening nausea and vomiting and underwent emergent nephrectomy, lymph node dissection, and colostomy due to a necrotic colon. Her condition declined over the next four months due to lung and brain metastases, infections, and other complications until she passed away.

Keywords: bedside ultrasound, echocardiography, emergency medicine, left atrial myxoma

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Authors: I. Hosni, L. Bennaceur Farah, N. Saber, R Bennaceur

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Soil moisture content is a key variable in many environmental sciences. Even though it represents a small proportion of the liquid freshwater on Earth, it modulates interactions between the land surface and the atmosphere, thereby influencing climate and weather. Accurate modeling of the above processes depends on the ability to provide a proper spatial characterization of soil moisture. The measurement of soil moisture content allows assessment of soil water resources in the field of hydrology and agronomy. The second parameter in interaction with the radar signal is the geometric structure of the soil. Most traditional electromagnetic models consider natural surfaces as single scale zero mean stationary Gaussian random processes. Roughness behavior is characterized by statistical parameters like the Root Mean Square (RMS) height and the correlation length. Then, the main problem is that the agreement between experimental measurements and theoretical values is usually poor due to the large variability of the correlation function, and as a consequence, backscattering models have often failed to predict correctly backscattering. In this study, surfaces are considered as band-limited fractal random processes corresponding to a superposition of a finite number of one-dimensional Gaussian process each one having a spatial scale. Multiscale roughness is characterized by two parameters, the first one is proportional to the RMS height, and the other one is related to the fractal dimension. Soil moisture is related to the complex dielectric constant. This multiscale description has been adapted to two-dimensional profiles using the bi-dimensional wavelet transform and the Mallat algorithm to describe more correctly natural surfaces. We characterize the soil surfaces and sub-surfaces by a three layers geo-electrical model. The upper layer is described by its dielectric constant, thickness, a multiscale bi-dimensional surface roughness model by using the wavelet transform and the Mallat algorithm, and volume scattering parameters. The lower layer is divided into three fictive layers separated by an assumed plane interface. These three layers were modeled by an effective medium characterized by an apparent effective dielectric constant taking into account the presence of air pockets in the soil. We have adopted the 2D multiscale three layers small perturbations model including, firstly air pockets in the soil sub-structure, and then a vegetable canopy in the soil surface structure, that is to simulate the radar backscattering. A sensitivity analysis of backscattering coefficient dependence on multiscale roughness and new soil moisture has been performed. Later, we proposed to change the dielectric constant of the multilayer medium because it takes into account the different moisture values of each layer in the soil. A sensitivity analysis of the backscattering coefficient, including the air pockets in the volume structure with respect to the multiscale roughness parameters and the apparent dielectric constant, was carried out. Finally, we proposed to study the behavior of the backscattering coefficient of the radar on a soil having a vegetable layer in its surface structure.

Keywords: multiscale, bidimensional, wavelets, backscattering, multilayer, SPM, air pockets

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Authors: Sardorbek Numonov, Hyohun Kim, Dongwha Shin, Yeonseok Kim, Ji-Su Ahn, Dongeun Choi, Byung-Woo Hong

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The detection of curvilinear structures often plays an important role in the analysis of images. In particular, it is considered as a crucial step for the diagnosis of chronic respiratory diseases to localize the fissures in chest CT imagery where the lung is divided into five lobes by the fissures that are characterized by linear features in appearance. However, the characteristic linear features for the fissures are often shown to be subtle due to the high intensity variability, pathological deformation or image noise involved in the imaging procedure, which leads to the uncertainty in the quantification of anatomical or functional properties of the lung. Thus, it is desired to enhance the linear features present in the chest CT images so that the distinctiveness in the delineation of the lobe is improved. We propose a recursive diffusion process that prefers coherent features based on the analysis of structure tensor in an anisotropic manner. The local image features associated with certain scales and directions can be characterized by the eigenanalysis of the structure tensor that is often regularized via isotropic diffusion filters. However, the isotropic diffusion filters involved in the computation of the structure tensor generally blur geometrically significant structure of the features leading to the degradation of the characteristic power in the feature space. Thus, it is required to take into consideration of local structure of the feature in scale and direction when computing the structure tensor. We apply an anisotropic diffusion in consideration of scale and direction of the features in the computation of the structure tensor that subsequently provides the geometrical structure of the features by its eigenanalysis that determines the shape of the anisotropic diffusion kernel. The recursive application of the anisotropic diffusion with the kernel the shape of which is derived from the structure tensor leading to the anisotropic scale-space where the geometrical features are preserved via the eigenanalysis of the structure tensor computed from the diffused image. The recursive interaction between the anisotropic diffusion based on the geometry-driven kernels and the computation of the structure tensor that determines the shape of the diffusion kernels yields a scale-space where geometrical properties of the image structure are effectively characterized. We apply our recursive anisotropic diffusion algorithm to the detection of curvilinear structure in the chest CT imagery where the fissures present curvilinear features and define the boundary of lobes. It is shown that our algorithm yields precise detection of the fissures while overcoming the subtlety in defining the characteristic linear features. The quantitative evaluation demonstrates the robustness and effectiveness of the proposed algorithm for the detection of fissures in the chest CT in terms of the false positive and the true positive measures. The receiver operating characteristic curves indicate the potential of our algorithm as a segmentation tool in the clinical environment. This work was supported by the MISP(Ministry of Science and ICT), Korea, under the National Program for Excellence in SW (20170001000011001) supervised by the IITP(Institute for Information and Communications Technology Promotion).

Keywords: anisotropic diffusion, chest CT imagery, chronic respiratory disease, curvilinear structure, fissure detection, structure tensor

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Authors: Sachil Kumar, Anoop Kumar Verma, Wahid Ali, Uma Shankar Singh

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Globally approximately 55.3 million people die each year. In the India there were 95 lakh annual deaths in 2013. The number of deaths resulted from homicides, suicides and unintentional injuries in the same period was about 5.7 lakh. The ever-increasing crime rate necessitated the development of methods for determining time since death. An erroneous time of death window can lead investigators down the wrong path or possibly focus a case on an innocent suspect. In this regard a research was carried out by analyzing the temperature dependent degradation of a Cardiac Troponin-T protein (cTnT) in the myocardium postmortem as a marker for time since death. Cardiac tissue samples were collected from (n=6) medico-legal autopsies, (in the Department of Forensic Medicine and Toxicology, King George’s Medical University, Lucknow India) after informed consent from the relatives and studied post-mortem degradation by incubation of the cardiac tissue at room temperature (20±2 OC), 12 0C, 25 0C and 37 0C for different time periods ((~5, 26, 50, 84, 132, 157, 180, 205, and 230 hours). The cases included were the subjects of road traffic accidents (RTA) without any prior history of disease who died in the hospital and their exact time of death was known. The analysis involved extraction of the protein, separation by denaturing gel electrophoresis (SDS-PAGE) and visualization by Western blot using cTnT specific monoclonal antibodies. The area of the bands within a lane was quantified by scanning and digitizing the image using Gel Doc. The data shows a distinct temporal profile corresponding to the degradation of cTnT by proteases found in cardiac muscle. The disappearance of intact cTnT and the appearance of lower molecular weight bands are easily observed. Western blot data clearly showed the intact protein at 42 kDa, two major (27 kDa, 10kDa) fragments, two additional minor fragments (32 kDa) and formation of low molecular weight fragments as time increases. At 12 0C the intensity of band (intact cTnT) decreased steadily as compared to RT, 25 0C and 37 0C. Overall, both PMI and temperature had a statistically significant effect where the greatest amount of protein breakdown was observed within the first 38 h and at the highest temperature, 37 0C. The combination of high temperature (37 0C) and long Postmortem interval (105.15 hrs) had the most drastic effect on the breakdown of cTnT. If the percent intact cTnT is calculated from the total area integrated within a Western blot lane, then the percent intact cTnT shows a pseudo-first order relationship when plotted against the log of the time postmortem. These plots show a good coefficient of correlation of r = 0.95 (p=0.003) for the regression of the human heart at different temperature conditions. The data presented demonstrates that this technique can provide an extended time range during which Postmortem interval can be more accurately estimated.

Keywords: degradation, postmortem interval, proteolysis, temperature, troponin

Procedia PDF Downloads 362

Authors: Fernanda Gonçalves, Karla Alcântara, Vanessa Moura, Patrícia Nolasco, Jorge Kalil, Maristela Hernandez

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Introduction: Atherosclerosis is a chronic disease where two striking features are observed: retention of lipids and inflammation. Understanding the interaction between immune cells and lipoproteins involved in atherogenesis are urgent challenges, since cardiovascular diseases are the leading cause of death worldwide. Macrophages are critical to the development of atherosclerotic plaques and in the perpetuation of inflammation in these lesions. These cells are also directly involved in unstable plaque rupture. Recently different populations of macrophages are being identified in atherosclerotic lesions. Although the presence of M2 macrophages (macrophages activated by the alternative pathway, eg. The IL-4) has been identified, the function of these cells in atherosclerosis is not yet defined. M2 macrophages have a high endocytic capacity, they promote remodeling of tissues and to have anti-inflammatory activity. However, in atherosclerosis, especially unstable plaques, severe inflammatory reaction, accumulation of cellular debris and intense degradation of the tissue is observed. Thus, it is possible that the M2 macrophages have altered function (phenotype) in atherosclerosis. Objective: Our aim is to evaluate if the presence of oxidized LDL alters the phenotype and function of M2 macrophages in vitro. Methods: For this, we will evaluate whether the addition of lipoprotein in M2 macrophages differentiated in vitro with IL -4 induces 1) a reduction in the secretion of anti-inflammatory cytokines (CBA and ELISA), 2) secretion of inflammatory cytokines (CBA and ELISA), 3) expression of cell activation markers (Flow cytometry), 4) alteration in gene expression of molecules adhesion and extracellular matrix (Real-Time PCR) and 5) Matrix degradation (confocal microscopy). Results: In oxLDL stimulated M2 macrophages cultures we did not find any differences in the expression of the cell surface markers tested, including: HLA-DR, CD80, CD86, CD206, CD163 and CD36. Also, cultures stimulated with oxLDL had similar phagocytic capacity when compared to unstimulated cells. However, in the supernatant of these cultures an increase in the secretion of the pro-inflammatory cytokine IL-8 was detected. No significant changes where observed in IL-6, IL-10, IL-12 and IL-1b levels. The culture supernatant also induced massive extracellular matrix (produced by mouse embryo fibroblast) filaments degradation. When evaluating the expression of 84 extracellular matrix and adhesion molecules genes, we observed that the stimulation of oxLDL in M2 macrophages decreased 47% of the genes and increased the expression of only 3% of the genes. In particular we noted that oxLDL inhibit the expression of 60% of the genes constituents of extracellular matrix and collagen expressed by these cells, including fibronectin1 and collagen VI. We also observed a decrease in the expression of matrix protease inhibitors, such as TIMP 2. On the opposite, the matricellular protein thrombospondin had a 12 fold increase in gene expression. In the presence of native LDL 90% of the genes had no altered expression. Conclusion: M2 macrophages stimulated with oxLDL secrete the pro-inflammatory cytokine IL-8, have an altered extracellular matrix constituents gene expression, and promote the degradation of extracellular matrix. M2 macrophages may contribute to the perpetuation of inflammation in atherosclerosis and to plaque rupture.

Keywords: atherosclerosis, LDL, macrophages, m2

Procedia PDF Downloads 306

Authors: Nikitha Francis, Anjana Hoode, Vinitha George, Jayashree S. Bhat

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The interaction between cognition and language, referred as cognitive-communication, is very intricate, involving several mental processes such as perception, memory, attention, lexical retrieval, decision making, motor planning, self-monitoring and knowledge. Cognitive-communication disorders are difficulties in communicative competencies that result from underlying cognitive impairments of attention, memory, organization, information processing, problem solving, and executive functions. Traumatic brain injury (TBI) is an acquired, non - progressive condition, resulting in distinct deficits of cognitive communication abilities such as naming, word-finding, self-monitoring, auditory recognition, attention, perception and memory. Cognitive-communication intervention in TBI is individualized, in order to enhance the person’s ability to process and interpret information for better functioning in their family and community life. The present case report illustrates the cognitive-communicative behaviors and the intervention outcomes of an adult with TBI, who was brought to the Department of Audiology and Speech Language Pathology, with cognitive and communicative disturbances, consequent to road traffic accident. On a detailed assessment, she showed naming deficits along with perseverations and had severe difficulty in recalling the details of the accident, her house address, places she had visited earlier, names of people known to her, as well as the activities she did each day, leading to severe breakdowns in her communicative abilities. She had difficulty in initiating, maintaining and following a conversation. She also lacked orientation to time and place. On administration of the Manipal Manual of Cognitive Linguistic Abilities (MMCLA), she exhibited poor performance on tasks related to visual and auditory perception, short term memory, working memory and executive functions. She attended 20 sessions of cognitive-communication intervention which followed a domain-general, adaptive training paradigm, with tasks relevant to everyday cognitive-communication skills. Compensatory strategies such as maintaining a dairy with reminders of her daily routine, names of people, date, time and place was also recommended. MMCLA was re-administered and her performance in the tasks showed significant improvements. Occurrence of perseverations and word retrieval difficulties reduced. She developed interests to initiate her day-to-day activities at home independently, as well as involve herself in conversations with her family members. Though she lacked awareness about her deficits, she actively involved herself in all the therapy activities. Rehabilitation of moderate to severe head injury patients can be done effectively through a holistic cognitive retraining with a focus on different cognitive-linguistic domains. Selection of goals and activities should have relevance to the functional needs of each individual with TBI, as highlighted in the present case report.

Keywords: cognitive-communication, executive functions, memory, traumatic brain injury

Procedia PDF Downloads 316

Authors: Nickolas A. Stewart, Donald C. Hefelfinger, Garrett V. Brittain, Timothy C. Frommeyer, Adrienne Stolfi

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Orthopedic surgery is currently considered one of the most competitive specialties that medical students can apply to for residency training. As evidenced by increasing United States Medical Licensing Examination (USMLE) scores, overall grades, and publication, presentation, and abstract numbers, this specialty is getting increasingly competitive. The recent change of USMLE Step 1 scores to pass/fail has resulted in additional challenges for medical students planning to apply for orthopedic residency. Until now, these scores have been a tool used by residency programs to screen applicants as an initial factor to determine the strength of their application. With USMLE STEP 1 converting to a pass/fail grading criterion, the question remains as to what will take its place on the ERAS application. The primary objective of this study is to determine the trends in the number of research projects, abstracts, presentations, and publications among orthopedic residency applicants. Secondly, this study seeks to determine if there is a relationship between the number of research projects, abstracts, presentations, and publications, and match rates. The researchers utilized the National Resident Matching Program's Charting Outcomes in the Match between 2007 and 2022 to identify mean publications and research project numbers by allopathic and osteopathic US orthopedic surgery senior applicants. A paired t test was performed between the mean number of publications and research projects by matched and unmatched applicants. Additionally, simple linear regressions within matched and unmatched applicants were used to determine the association between year and number of abstracts, presentations, and publications, and a number of research projects. For determining whether the increase in the number of abstracts, presentations, and publications, and a number of research projects is significantly different between matched and unmatched applicants, an analysis of covariance is used with an interaction term added to the model, which represents the test for the difference between the slopes of each group. The data shows that from 2007 to 2022, the average number of research publications increased from 3 to 16.5 for matched orthopedic surgery applicants. The paired t-test had a significant p-value of 0.006 for the number of research publications between matched and unmatched applicants. In conclusion, the average number of publications for orthopedic surgery applicants has significantly increased for matched and unmatched applicants from 2007 to 2022. Moreover, this increase has accelerated in recent years, as evidenced by an increase of only 1.5 publications from 2007 to 2001 versus 5.0 publications from 2018 to 2022. The number of abstracts, presentations, and publications is a significant factor regarding an applicant's likelihood to successfully match into an orthopedic residency program. With USMLE Step 1 being converted to pass/fail, the researchers expect students and program directors will place increased importance on additional factors that can help them stand out. This study demonstrates that research will be a primary component in stratifying future orthopedic surgery applicants. In addition, this suggests the average number of research publications will continue to accelerate. Further study is required to determine whether this growth is sustainable.

Keywords: publications, orthopedic surgery, research, residency applications

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Authors: Leslie Raphael de M. Ferraz, Salvana Priscylla M. Costa, Tarcyla de A. Gomes, Giovanna Christinne R. M. Schver, Cristóvão R. da Silva, Magaly Andreza M. de Lyra, Danilo Augusto F. Fontes, Larissa A. Rolim, Amanda Carla Q. M. Vieira, Miracy M. de Albuquerque, Pedro J. Rolim-Neto

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Efavirenz (EFV) is a drug used as first-line treatment of AIDS. However, it has poor aqueous solubility and wettability, presenting problems in the gastrointestinal tract absorption and bioavailability. One of the most promising strategies to improve the solubility is the use of solid dispersions (SD). Therefore, this study aimed to characterize SD EFZ with the polymers: PVP-K30, PVPVA 64 and SOLUPLUS in order to find an optimal formulation to compose a future pharmaceutical product for AIDS therapy. Initially, Physical Mixtures (PM) and SD with the polymers were obtained containing 10, 20, 50 and 80% of drug (w/w) by the solvent method. The best formulation obtained between the SD was selected by in vitro dissolution test. Finally, the drug-carrier system chosen, in all ratios obtained, were analyzed by the following techniques: Differential Scanning Calorimetry (DSC), polarization microscopy, Scanning Electron Microscopy (SEM) and spectrophotometry of absorption in the region of infrared (IR). From the dissolution profiles of EFV, PM and SD, the values of area Under The Curve (AUC) were calculated. The data showed that the AUC of all PM is greater than the isolated EFV, this result is derived from the hydrophilic properties of the polymers thus favoring a decrease in surface tension between the drug and the dissolution medium. In adittion, this ensures an increasing of wettability of the drug. In parallel, it was found that SD whom had higher AUC values, were those who have the greatest amount of polymer (with only 10% drug). As the amount of drug increases, it was noticed that these results either decrease or are statistically similar. The AUC values of the SD using the three different polymers, followed this decreasing order: SD PVPVA 64-EFV 10% > SD PVP-K30-EFV 10% > SD Soluplus®-EFV 10%. The DSC curves of SD’s did not show the characteristic endothermic event of drug melt process, suggesting that the EFV was converted to its amorphous state. The analysis of polarized light microscopy showed significant birefringence of the PM’s, but this was not observed in films of SD’s, thus suggesting the conversion of the drug from the crystalline to the amorphous state. In electron micrographs of all PM, independently of the percentage of the drug, the crystal structure of EFV was clearly detectable. Moreover, electron micrographs of the SD with the two polymers in different ratios investigated, we observed the presence of particles with irregular size and morphology, also occurring an extensive change in the appearance of the polymer, not being possible to differentiate the two components. IR spectra of PM corresponds to the overlapping of polymer and EFV bands indicating thereby that there is no interaction between them, unlike the spectra of all SD that showed complete disappearance of the band related to the axial deformation of the NH group of EFV. Therefore, this study was able to obtain a suitable formulation to overcome the solubility limitations of the EFV, since SD PVPVA 64-EFZ 10% was chosen as the best system in delay crystallization of the prototype, reaching higher levels of super saturation.

Keywords: characterization, dissolution, Efavirenz, solid dispersions

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Authors: Kimberly M. Cacciato, Steven J. Singer, Allison R. Shapiro, Julianna F. Kamenakis

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This study examines the dynamics of communication among researchers and participants who have various levels of hearing, use multiple languages, have various disabilities, and who come from different social strata. This qualitative methodological study focuses on the strategies employed in an ethnographic research study examining the communication choices of six sets of parents who have Deaf-Disabled children. The participating families varied in their communication strategies and preferences including the use of American Sign Language (ASL), visual-gestural communication, multiple spoken languages, and pidgin forms of each of these. The research team consisted of two undergraduate students proficient in ASL and a Deaf principal investigator (PI) who uses ASL and speech as his main modes of communication. A third Hard-of-Hearing undergraduate student fluent in ASL served as an objective facilitator of the data analysis. The team created reflexive journals by audio recording, free writing, and responding to team-generated prompts. They discussed interactions between the members of the research team, their evolving relationships, and various social and linguistic power differentials. The researchers reflected on communication during data collection, their experiences with one another, and their experiences with the participating families. Reflexive journals totaled over 150 pages. The outside research assistant reviewed the journals and developed follow up open-ended questions and prods to further enrich the data. The PI and outside research assistant used NVivo qualitative research software to conduct open inductive coding of the data. They chunked the data individually into broad categories through multiple readings and recognized recurring concepts. They compared their categories, discussed them, and decided which they would develop. The researchers continued to read, reduce, and define the categories until they were able to develop themes from the data. The research team found that the various communication backgrounds and skills present greatly influenced the dynamics between the members of the research team and with the participants of the study. Specifically, the following themes emerged: (1) students as communication facilitators and interpreters as barriers to natural interaction, (2) varied language use simultaneously complicated and enriched data collection, and (3) ASL proficiency and professional position resulted in a social hierarchy among researchers and participants. In the discussion, the researchers reflected on their backgrounds and internal biases of analyzing the data found and how social norms or expectations affected the perceptions of the researchers in writing their journals. Through this study, the research team found that communication and language skills require significant consideration when working with multiple and complex communication modes. The researchers had to continually assess and adjust their data collection methods to meet the communication needs of the team members and participants. In doing so, the researchers aimed to create an accessible research setting that yielded rich data but learned that this often required compromises from one or more of the research constituents.

Keywords: American Sign Language, complex communication, deaf-disabled, methodology

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Authors: Ishan Naidu, Jessica Ryvlin, Devin Videlefsky

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Introduction: Back pain is a leading cause of years lived with disability and economic burden, exceeding over $20 billion in healthcare costs not including indirect costs such as absence from work and caregiving. The multifactorial nature of back pain leads to treatment modalities administered by a variety of specialists, which are often disjointed. Multiple studies have found that patients receiving delayed physical therapy for lower back pain had higher medical-related costs from increased health service utilization as well as a reduced improvement in pain severity compared to early management. Uncoordinated health care delivery can exacerbate the physical and economic toll of the chronic condition, thus improvements in interdisciplinary, shared decision-making may improve outcomes. Objective: To assess whether a multidisciplinary spine clinic (MSC), consisting of orthopedic surgery, neurosurgery, pain medicine, and physiatry, alters interventional and non-interventional planning and treatment compared to a traditional unidisciplinary spine clinic (USC) including only orthopedic surgery. Methods: We conducted a retrospective cohort study with patients initially presenting for spine care to orthopedic surgeons between July 1, 2018 to June 30, 2019. Time to treatment recommendation, time to treatment and rates of treatment recommendations were assessed, including physical therapy, injections and surgery. Treatment rates were compared between MSC and USC using Pearson’s chi-square test logistic regression. Time to treatment recommendation and time to treatment were compared using log-rank test and Cox proportional hazard regression. All analyses were repeated for the propensity score (PS) matched subsample. Results: This study included 1,764 patients, with 692 at MSC and 1,072 at USC. Patients in MSC were more likely to be recommended injection when compared to USC (8.5% vs. 5.4%, p=0.01). When adjusted for confounders, the likelihood of injection recommendation remained greater in MSC than USC (Odds ratio [OR]=2.22, 95% CI: (1.39, 3.53), p=0.001). MSC was also associated with a shorter time to receiving injection recommendation versus USC (median: 21 vs. 32 days, log-rank: p<0.001; hazard ratio [HR]=1.90, 95% CI: (1.25, 2.90), p=0.003). MSC was associated with a higher likelihood of injection treatment (OR=2.27, 95% CI: (1.39, 3.73), p=0.001) and shorter lead time (HR=1.98, 95% CI: (1.27, 3.09), p=0.003). PS-matched analyses yielded similar conclusions. Conclusions: Care delivered at a multidisciplinary spine clinic was associated with a higher likelihood of recommending injection and a shorter lead time to injection administration when compared to a traditional unidisciplinary spine surgery clinic. Multidisciplinary clinics may facilitate coordinated care amongst different specialties resulting in increased utilization of less invasive treatment modalities while also improving care efficiency. The multidisciplinary clinic model is an important advancement in care delivery and communication, which can be used as a powerful method of improving patient outcomes as treatment guidelines evolve.

Keywords: coordinated care, epidural steroid injection, multi-disciplinary, non-invasive

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Authors: M. Salvador, J. C. Martinez-Garcia, A. Moyano, M. C. Blanco-Lopez, M. Rivas

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Biosensors play a crucial role in the detection of molecules nowadays due to their advantages of user-friendliness, high selectivity, the analysis in real time and in-situ applications. Among them, Lateral Flow Immunoassays (LFIAs) are presented among technologies for point-of-care bioassays with outstanding characteristics such as affordability, portability and low-cost. They have been widely used for the detection of a vast range of biomarkers, which do not only include proteins but also nucleic acids and even whole cells. Although the LFIA has traditionally been a positive/negative test, tremendous efforts are being done to add to the method the quantifying capability based on the combination of suitable labels and a proper sensor. One of the most successful approaches involves the use of magnetic sensors for detection of magnetic labels. Bringing together the required characteristics mentioned before, our research group has developed a biosensor to detect biomolecules. Superparamagnetic nanoparticles (SPNPs) together with LFIAs play the fundamental roles. SPMNPs are detected by their interaction with a high-frequency current flowing on a printed micro track. By means of the instant and proportional variation of the impedance of this track provoked by the presence of the SPNPs, quantitative and rapid measurement of the number of particles can be obtained. This way of detection requires no external magnetic field application, which reduces the device complexity. On the other hand, the major limitations of LFIAs are that they are only qualitative or semiquantitative when traditional gold or latex nanoparticles are used as color labels. Moreover, the necessity of always-constant ambient conditions to get reproducible results, the exclusive detection of the nanoparticles on the surface of the membrane, and the short durability of the signal are drawbacks that can be advantageously overcome with the design of magnetically labeled LFIAs. The approach followed was to coat the SPIONs with a specific monoclonal antibody which targets the protein under consideration by chemical bonds. Then, a sandwich-type immunoassay was prepared by printing onto the nitrocellulose membrane strip a second antibody against a different epitope of the protein (test line) and an IgG antibody (control line). When the sample flows along the strip, the SPION-labeled proteins are immobilized at the test line, which provides magnetic signal as described before. Preliminary results using this practical combination for the detection and quantification of the Prostatic-Specific Antigen (PSA) shows the validity and consistency of the technique in the clinical range, where a PSA level of 4.0 ng/mL is the established upper normal limit. Moreover, a LOD of 0.25 ng/mL was calculated with a confident level of 3 according to the IUPAC Gold Book definition. Its versatility has also been proved with the detection of other biomolecules such as troponin I (cardiac injury biomarker) or histamine.

Keywords: biosensor, lateral flow immunoassays, point-of-care devices, superparamagnetic nanoparticles

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Authors: Oleg Reva, Ilya Korotetskiy, Marina Lankina, Murat Kulmanov, Aleksandr Ilin

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Molecular docking approaches are widely used for design of new antibiotics and modeling of antibacterial activities of numerous ligands which bind specifically to active centers of indispensable enzymes and/or key signaling proteins of pathogens. Widespread drug resistance among pathogenic microorganisms calls for development of new antibiotics specifically targeting important metabolic and information pathways. A generally recognized problem is that almost all molecular targets have been identified already and it is getting more and more difficult to design innovative antibacterial compounds to combat the drug resistance. A promising way to overcome the drug resistance problem is an induction of reversion of drug resistance by supplementary medicines to improve the efficacy of the conventional antibiotics. In contrast to well established computer-based drug design, modeling of drug resistance reversion still is in its infancy. In this work, we proposed an approach to identification of compensatory genetic variants reducing the fitness cost associated with the acquisition of drug resistance by pathogenic bacteria. The approach was based on an analysis of the population genetic of Mycobacterium tuberculosis and on results of experimental modeling of the drug resistance reversion induced by a new anti-tuberculosis drug FS-1. The latter drug is an iodine-containing nanomolecular complex that passed clinical trials and was admitted as a new medicine against MDR-TB in Kazakhstan. Isolates of M. tuberculosis obtained on different stages of the clinical trials and also from laboratory animals infected with MDR-TB strain were characterized by antibiotic resistance, and their genomes were sequenced by the paired-end Illumina HiSeq 2000 technology. A steady increase in sensitivity to conventional anti-tuberculosis antibiotics in series of isolated treated with FS-1 was registered despite the fact that the canonical drug resistance mutations identified in the genomes of these isolates remained intact. It was hypothesized that the drug resistance phenotype in M. tuberculosis requires an adjustment of activities of many genes to compensate the fitness cost of the drug resistance mutations. FS-1 cased an aggravation of the fitness cost and removal of the drug-resistant variants of M. tuberculosis from the population. This process caused a significant increase in genetic heterogeneity of the Mtb population that was not observed in the positive and negative controls (infected laboratory animals left untreated and treated solely with the antibiotics). A large-scale search for linkage disequilibrium associations between the drug resistance mutations and genetic variants in other genomic loci allowed identification of target proteins, which could be influenced by supplementary drugs to increase the fitness cost of the drug resistance and deprive the drug-resistant bacterial variants of their competitiveness in the population. The approach will be used to improve the efficacy of FS-1 and also for computer-based design of new drugs to combat drug-resistant infections.

Keywords: complete genome sequencing, computational modeling, drug resistance reversion, Mycobacterium tuberculosis

Procedia PDF Downloads 241

Authors: Rabab Makki

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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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Authors: Richele P. Severino, Maria M. F. Alchaar, Lorena R. F. De Sousa, Patrik S. Vital, Ana G. Silva, Rosy I. M. A. Ribeiro

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Recognized as a global biodiversity hotspot, the Cerrado (Brazil) presents an extreme abundance of endemic species and it is considered to be one of the biologically richest tropical savanna regions in the world. Erythroxylum genus is found in Cerrado and chemically is characterized by the presence of tropane alkaloids, among them cocaine, a natural alkaloid produced by Erythroxylum coca Lam., which was used as a local anesthetic in small surgeries. However, cocaine gained notoriety due to its psychoactive activity in the Central Nervous System (CNS), becoming one of the major problems of public health today. Some species of Erythroxylum are referred to in the literature as having pharmacological potential, which provide alkaloids, terpenoids, and flavonoids. E. vacciniifolium Mart., commonly known as 'catuaba', is used as a central nervous system stimulant and has aphrodisiac properties and E. pelleterianum A. St.-Hil. in the treatment of stomach pains. Already E. myrsinites Mart. and E. suberosum A. St.-Hil. are used in the tannery industry. Species of Erythroxylum are also used in folk medicine for various diseases, against diabetes, antiviral, fungicidal, cytotoxicity, among others. The Cerrado is recognized as the richer savannah in the world in biodiversity but little explored from the chemical view. In our on-going study of the chemistry of Erythroxylum genus, we have investigated four specimens collected in central Cerrado of Brazil: E. campestre (EC), E. deciduum (ED), E. suberosum (ES) and E. tortuosum (ET). The cytotoxic activity of extracts was evaluated using HeLa cells, in vitro assays. The chemical investigation was performed preparing the extracts using n-hexane (H), dichloromethane (D), ethyl acetate (E) and methanol (M). The cells were treated with increasing concentrations of extracts (50, 75 and 100 μg/mL) diluted in DMSO (1%) and DMEM (0.5% FBS and 1% P/S). The IC₅₀ values were determined measured spectrophotometrically at 570 nm, after incubation of HeLa cell line for 48 hours using the MTT (SIGMA M5655), and calculated by nonlinear regression analysis using GraphPad Prism software. All the assays were done in triplicate and repeated at least two times. The cytotoxic assays showed some promising results with IC₅₀ values less than 100 μg/mL (ETD = 38.5 μg/mL; ETM = 92.3 μg/mL; ESM = 67.8 μg/mL; ECD = 24.0 μg/mL; ECM = 32.9; EDA = 44.2 μg/mL). The chemical profile study of ethyl acetate (E) and methanolic (M) extracts of E. tortuosum leaves was performed by LC-MS, and the structures of the compounds were determined by analysis of ¹H, HSQC and HMBC spectra, and confirmed by comparison with the literature data. The investigation led to six substances: α-amyrin, β-amyrin, campesterol, stigmastan-3,5-diene, β-sitosterol and 7,4’-di-O-methylquercetin-3-O-β-rutinoside, with flavonoid the major compound of extracts. By alkaline extraction of the methanolic extract, it was possible to identify three alkaloids: tropacocaine, cocaine and 6-methoxy-8-methyl-8-azabicyclo[3.2.1]octan-3-ol. The results obtained are important for the chemical knowledge of the Cerrado biodiversity and brought a contribution to the chemistry of Erythroxylum genus.

Keywords: cytotoxicity, Erythroxylum, chemical profile, secondary metabolites

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Authors: Rahaba Marima, Clement Penny

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The Health-related quality of life (HRQoL) for HIV positive patients has improved since the introduction of the highly active antiretroviral treatment (HAART). However, in the present HAART era, HIV co-morbidities such as lung cancer, a non-AIDS (NAIDS) defining cancer have been documented to be on the rise. Under normal physiological conditions, cells grow, repair and proliferate through the cell-cycle as cellular homeostasis is important in the maintenance and proper regulation of tissues and organs. Contrarily, the deregulation of the cell-cycle is a hallmark of cancer, including lung cancer. The association between lung cancer and the use of HAART components such as Efavirenz (EFV) is poorly understood. This study aimed at elucidating the effects of EFV on the cell-cycle genes’ expression in lung cancer. For this purpose, the human cell-cycle gene array composed of 84 genes was evaluated on both normal lung fibroblasts (MRC-5) cells and adenocarcinoma (A549) lung cells, in response to 13µM EFV or 0.01% vehicle. The ±2 up or down fold change was used as a basis of target selection, with p < 0.05. Additionally, RT-qPCR was done to validate the gene array results. Next, In-silico bio-informatics tools, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Reactome, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Ingenuity Pathway Analysis (IPA) were used for gene/gene interaction studies as well as to map the molecular and biological pathways influenced by the identified targets. Interestingly, the DNA damage response (DDR) pathway genes such as p53, Ataxia telangiectasia mutated and Rad3 related (ATR), Growth arrest and DNA damage inducible alpha (GADD45A), HUS1 checkpoint homolog (HUS1) and Role of radiation (RAD) genes were shown to be upregulated following EFV treatment, as revealed by STRING analysis. Additionally, functional enrichment analysis by the KEGG pathway revealed that most of the differentially expressed gene targets function at the cell-cycle checkpoint such as p21, Aurora kinase B (AURKB) and Mitotic Arrest Deficient-Like 2 (MAD2L2). Core analysis by IPA revealed that p53 downstream targets such as survivin, Bcl2, and cyclin/cyclin dependent kinases (CDKs) complexes are down-regulated, following exposure to EFV. Furthermore, Reactome analysis showed a significant increase in cellular response to stress genes, DNA repair genes, and apoptosis genes, as observed in both normal and cancerous cells. These findings implicate the genotoxic effects of EFV on lung cells, provoking the DDR pathway. Notably, the constitutive expression of this pathway (DDR) often leads to uncontrolled cell proliferation and eventually tumourigenesis, which could be the attribute of HAART components’ (such as EFV) effect on human cancers. Targeting the cell-cycle and its regulation holds a promising therapeutic intervention to the potential HAART associated carcinogenesis, particularly lung cancer.

Keywords: cell-cycle, DNA damage response, Efavirenz, lung cancer

Procedia PDF Downloads 126