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Authors: Murray David Schane

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Though years of clinical encounters with patients with autism spectrum disorders and those with a schizoid personality the many defining diagnostic features shared between these conditions have been explored and current neurobiological differences have been reviewed; and, critical and different treatment strategies for each have been devised. The paper compares and contrasts the apparent similarities between autism spectrum disorders and the schizoid personality are found in these DSM descriptive categories: restricted range of social-emotional reciprocity; poor non-verbal communicative behavior in social interactions; difficulty developing and maintaining relationships; detachment from social relationships; lack of the desire for or enjoyment of close relationships; and preference for solitary activities. In this paper autism, fundamentally a communicative disorder, is revealed to present clinically as a pervasive aversive response to efforts to engage with or be engaged by others. Autists with the Asperger presentation typically have language but have difficulty understanding humor, irony, sarcasm, metaphoric speech, and even narratives about social relationships. They also tend to seek sameness, possibly to avoid problems of social interpretation. Repetitive behaviors engage many autists as a screen against ambient noise, social activity, and challenging interactions. Also in this paper, the schizoid personality is revealed as a pattern of social avoidance, self-sufficiency and apparent indifference to others as a complex psychological defense against a deep, long-abiding fear of appropriation and perverse manipulation. Neither genetic nor MRI studies have yet located the explanatory data that identifies the cause or the neurobiology of autism. Similarly, studies of the schizoid have yet to group that condition with those found in schizophrenia. Through presentations of clinical examples, the treatment of autists of the Asperger type is revealed to address the autist’s extreme social aversion which also precludes the experience of empathy. Autists will be revealed as forming social attachments but without the capacity to interact with mutual concern. Empathy will be shown be teachable and, as social avoidance relents, understanding of the meaning and signs of empathic needs that autists can recognize and acknowledge. Treatment of schizoids will be shown to revolve around joining empathically with the schizoid’s apprehensions about interpersonal, interactive proximity. Models of both autism and schizoid personality traits have yet to be replicated in animals, thereby eliminating the role of translational research in providing the kind of clues to behavioral patterns that can be related to genetic, epigenetic and neurobiological measures. But as these clinical examples will attest, treatment strategies have significant impact.

Keywords: autism spectrum, schizoid personality traits, neurobiological implications, critical diagnostic distinctions

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Authors: Cheyenne Johnson, Samantha Robinson, Christina Chant, Ann M. Mitchell, Carol Price, Carmel Clancy, Adam Searby, Deborah S. Finnell

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Introduction: Substance use along the continuum from at-risk use to a substance use disorder (SUD) contributes substantially to the burden of disease and related harms worldwide. There is a growing body of literature that highlights the lack of substance use related content in nursing curricula. Furthermore, there is also a lack of consensus on key competencies necessary for entry-level nurses. Globally, there is a lack of established nursing competencies related to prevention, health promotion, harm reduction and treatment of at-risk substance use and SUDs. At a critical time in public health, this gap in nursing curricula contributes to a lack of preparation for entry-level nurses to support people along the continuum of substance use. Thus, in practice, early opportunities for screening, support, and interventions may be missed. To address this gap, an international committee was convened to develop international entry-level nursing competencies specifying the knowledge, skills, and abilities that all nurses should possess in order to address the continuum of substance use. Methodology: An international steering committee, including representation from Canada, United States, United Kingdom, and Australia was established to lead this work over a one-year time period. The steering committee conducted a scoping review, undertaken to examine nursing competency frameworks, and to inform a competency structure that would guide this work. The next steps were to outline key competency areas and establish leaders for working groups to develop the competencies. In addition, a larger international committee was gathered to contribute to competency working groups, review the collective work and concur on the final document. Findings: A comprehensive framework was developed with competencies covering a wide spectrum of substance use across the lifespan and in the context of prevention, health promotion, harm reduction and treatment, including special populations. The development of this competency-based framework meets an identified need to provide guidance for universities, health authorities, policy makers, nursing regulators and other organizations that provide and support nursing education which focuses on care for patients and families with at-risk substance use and SUDs. Conclusion: Utilizing these global competencies as expected outcomes of an educational and skill building curricula for entry-level nurses holds great promise for incorporating evidence-informed training in the care and management of people across the continuum of substance use.

Keywords: addiction nursing, addiction nursing curriculum, competencies, substance use

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Authors: Mustafa Malki, Ewan R. Pearson

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Tools utilized by health care practitioners to flag potential adverse drug reactions secondary to drug-drug interactions ignore individual genetic variation, which has the potential to markedly alter the severity of these interactions. To our best knowledge, there have been limited published studies on the impact of genetic variation on drug-drug interactions. Therefore, our aim in this project is the discovery of previously unrecognized, clinically important drug-drug-gene interactions (DDGIs) within the list of most commonly used drug combinations in the UK. The UKBB database was utilized to identify the top most frequently prescribed drug combinations in the UK with at least one route of interaction (over than 200 combinations were identified). We have recognised 37 common and unique interacting genes considering all of our drug combinations. Out of around 600 potential genetic variants found in these 37 genes, 100 variants have met the selection criteria (common variant with minor allele frequency ≥ 5%, independence, and has passed HWE test). The association between these variants and the use of each of our top drug combinations has been tested with a case-control analysis under the log-additive model. As the data is cross-sectional, drug intolerance has been identified from the genotype distribution as presented by the lower percentage of patients carrying the risky allele and on the drug combination compared to those free of these risk factors and vice versa with drug tolerance. In GoDARTs database, the same list of common drug combinations identified by the UKBB was utilized here with the same list of candidate genetic variants but with the addition of 14 new SNPs so that we have a total of 114 variants which have met the selection criteria in GoDARTs. From the list of the top 200 drug combinations, we have selected 28 combinations where the two drugs in each combination are known to be used chronically. For each of our 28 combinations, three drug response phenotypes have been identified (drug stop/switch, dose decrease, or dose increase of any of the two drugs during their interaction). The association between each of the three phenotypes belonging to each of our 28 drug combinations has been tested against our 114 candidate genetic variants. The results show replication of four findings between both databases : (1) Omeprazole +Amitriptyline +rs2246709 (A > G) variant in CYP3A4 gene (p-values and ORs with the UKBB and GoDARTs respectively = 0.048,0.037,0.92,and 0.52 (dose increase phenotype)) (2) Simvastatin + Ranitidine + rs9332197 (T > C) variant in CYP2C9 gene (0.024,0.032,0.81, and 5.75 (drug stop/switch phenotype)) (3) Atorvastatin + Doxazosin + rs9282564 (T > C) variant in ABCB1 gene (0.0015,0.0095,1.58,and 3.14 (drug stop/switch phenotype)) (4) Simvastatin + Nifedipine + rs2257401 (C > G) variant in CYP3A7 gene (0.025,0.019,0.77,and 0.30 (drug stop/switch phenotype)). In addition, some other non-replicated, but interesting, significant findings were detected. Our work also provides a great source of information for researchers interested in DD, DG, or DDG interactions studies as it has highlighted the top common drug combinations in the UK with recognizing 114 significant genetic variants related to drugs' pharmacokinetic.

Keywords: adverse drug reactions, common drug combinations, drug-drug-gene interactions, pharmacogenomics

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Authors: Fiona Jensen, Barb Goodwin, Nancy Kleiman, Rhonda Usunier

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Background: Clinical simulation is now a common component in many health profession curricula in preparation for clinical practice. In the Rady Faculty of Health Sciences (RFHS) college leads in simulation and interprofessional (IP) education, planned an eight hour simulated hospital day shift, where seventy students from six health professions across two campuses, learned with each other in a safe, realistic environment. Learning about interprofessional collaboration, an expected competency for many health professions upon graduation, was a primary focus of the simulation event. Method: Faculty representatives from the Colleges of Nursing, Medicine, Pharmacy and Rehabilitation Sciences (Physical Therapy, Occupation Therapy, Respiratory Therapy) and Pharmacy worked together to plan the IP event in a simulation facility in the College of Nursing. Each college provided a faculty mentor to guide the same profession students. Students were placed in interprofessional teams consisting of a nurse, physician, pharmacist, and then sharing respiratory, occupational, and physical therapists across the team depending on the needs of the patients. Eight patient scenarios were role played by health profession students, who had been provided with their patient’s story shortly before the event. Each team was guided by a facilitator. Results and Outcomes: On the morning of the event, all students gathered in a large group to meet mentors and facilitators and have a brief overview of the six competencies for effective collaboration and the session objectives. The students assuming their same profession roles were provided with their patient’s chart at the beginning of the shift, met with their team, and then completed professional specific assessments. Shortly into the shift, IP team rounds began, facilitated by the team facilitator. During the shift, each patient role-played a spontaneous health incident, which required collaboration between the IP team members for assessment and management. The afternoon concluded with team rounds, a collaborative management plan, and a facilitated de-brief. Conclusions: During the de-brief sessions, students responded to set questions related to the session learning objectives and expressed many positive learning moments. We believe that we have a sustainable simulation IP collaborative learning opportunity, which can be embedded into curricula, and has the capacity to grow to include more health profession faculties and students. Opportunities are being explored in the RFHS at the administrative level, to offer this event more frequently in the academic year to reach more students. In addition, a formally structured event evaluation tool would provide important feedback and inform the qualitative feedback to event organizers and the colleges about the significance of the simulation event to student learning.

Keywords: simulation, collaboration, teams, interprofessional

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Authors: Danylo Brindak, Viktor Liashko, Olexander Chepurniy

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Despite considerable experience in implementation of the best international approaches and services within response to epidemy of multi-drug resistant tuberculosis, the results of situation analysis indicate the presence of faults in this area. In 2014, Ukraine (for the first time) was included in the world’s five countries with the highest level of drug-resistant tuberculosis. The effectiveness of its treatment constitutes only 35% in the country. In this context, the increase in allocation of funds to control the epidemic of multidrug-resistant tuberculosis does not produce perceptible positive results. During 2001-2016, only the Global Fund to fight AIDS, Tuberculosis, and Malaria allocated to Ukraine more than USD 521,3 million for programs of tuberculosis and HIV/AIDS control. However, current conditions in post-Semashko system create little motivation for rational use of resources or cost control at inpatient TB facilities. There is no motivation to reduce overdue hospitalization and to target resources to priority sectors of modern tuberculosis control, including a model of care focused on the patient. In the presence of a line-item budget at medical institutions, based on the input factors as the ratios of beds and staff, there is a passive disposal of budgetary funds by health care institutions and their employees who have no motivation to improve quality and efficiency of service provision. Outpatient treatment of tuberculosis is being implemented in Ukraine since 2011 and has many risks, namely creation of parallel systems, low consistency through dependence on funding for the project, reduced the role of the family doctor, the fragmentation of financing, etc. In terms of reforming approaches to health system financing, which began in Ukraine in late 2016, NGO Infection Control in Ukraine conducted piloting of a new, motivating method of remuneration of employees in primary health care. The innovative aspect of this funding mechanism is cost according to results of treatment. The existing method of payment on the basis of the standard per inhabitant (per capita ratio) was added with motivating costs according to results of work. The effectiveness of such treatment of TB patients at the outpatient stage is 90%, while in whole on the basis of a current system the effectiveness of treatment of newly diagnosed pulmonary TB with positive swab is around 60% in the country. Even though Ukraine has 5.24 TB beds per 10 000 citizens. Implemented pilot model of ambulatory treatment will be used for the creation of costs system according to results of activities, the integration of TB and primary health and social services and their focus on achieving results, the reduction of inpatient treatment of tuberculosis.

Keywords: health care reform, multi-drug resistant tuberculosis, outpatient treatment efficiency, tuberculosis

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Authors: A. Anastasiou, K. S. Tingay

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Background: Discovering suitable datasets is an important part of health research, particularly for projects working with clinical data from patients organized in cohorts (cohort data), but with the proliferation of so many national and international initiatives, it is becoming increasingly difficult for research teams to locate real world datasets that are most relevant to their project objectives. We present a method for identifying healthcare institutes in the European Union (EU) which may hold haemato-oncology (HO) data. A key enabler of this research was the bibInsight platform, a scientometric data management and analysis system developed by the authors at Swansea University. Method: A PubMed search was conducted using HO clinical terms taken from previous work. The resulting XML file was processed using the bibInsight platform, linking affiliations to the Global Research Identifier Database (GRID). GRID is an international, standardized list of institutions, including the city and country in which the institution exists, as well as a category of the main business type, e.g., Academic, Healthcare, Government, Company. Countries were limited to the 28 current EU members, and institute type to 'Healthcare'. An article was considered valid if at least one author was affiliated with an EU-based healthcare institute. Results: The PubMed search produced 21,310 articles, consisting of 9,885 distinct affiliations with correspondence in GRID. Of these articles, 760 were from EU countries, and 390 of these were healthcare institutes. One affiliation was excluded as being a veterinary hospital. Two EU countries did not have any publications in our analysis dataset. The results were analysed by country and by individual healthcare institute. Networks both within the EU and internationally show institutional collaborations, which may suggest a willingness to share data for research purposes. Geographical mapping can ensure that data has broad population coverage. Collaborations with industry or government may exclude healthcare institutes that may have embargos or additional costs associated with data access. Conclusions: Data reuse is becoming increasingly important both for ensuring the validity of results, and economy of available resources. The ability to identify potential, specific data sources from over twenty thousand articles in less than an hour could assist in improving knowledge of, and access to, data sources. As our method has not yet specified if these healthcare institutes are holding data, or merely publishing on that topic, future work will involve text mining of data-specific concordant terms to identify numbers of participants, demographics, study methodologies, and sub-topics of interest.

Keywords: data reuse, data discovery, data linkage, journal articles, text mining

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Authors: Tiffanie-Marie Borg, Yasmin Zeinolabediny, Nima Heidari, Ali Noorani, Mark Slevin, Angel Cullen, Stefano Olgiati, Alberto Zerbi, Alessandro Danovi, Adrian Wilson

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Knee Osteoarthritis (OA) is a critical cause of disability globally. In recent years, there has been growing interest in non-invasive treatments, such as intra-articular injection of micro-fragmented fat (MFAT), showing great potential in treating OA. Mesenchymal stem cells (MSCs), originating from pericytes of micro-vessels in MFAT, can differentiate into mesenchymal lineage cells such as cartilage, osteocytes, adipocytes, and osteoblasts. Secretion of growth factor and cytokines from MSCs have the capability to inhibit T cell growth, reduced pain and inflammation, and create a micro-environment that through paracrine signaling, can promote joint repair and cartilage regeneration. Here we have shown, for the first time, data supporting the hypothesis that women respond better in terms of improvements in pain and function to MFAT injection compared to men. Historically, women have been underrepresented in studies, and studies with both sexes regularly fail to analyse the results by sex. To mitigate this bias and quantify it, we describe a technique using reproducible statistical analysis and replicable results with Open Access statistical software R to calculate the magnitude of this difference. Genetic, hormonal, environmental, and age factors play a role in our observed difference between the sexes. This observational, intention-to-treat study included the complete sample of 456 patients who agreed to be scored for pain (visual analogue scale (VAS)) and function (Oxford knee score (OKS)) at baseline regardless of subsequent changes to adherence or status during follow-up. We report that a significantly larger number of women responded to treatment than men: [90% vs. 60% change in VAS scores with 87% vs. 65% change in OKS scores, respectively]. Women overall had a stronger positive response to treatment with reduced pain and improved mobility and function. Pre-injection, our cohort of women were in more pain with worse joint function which is quite common to see in orthopaedics. However, during the 2-year follow-up, they consistently maintained a lower incidence of discomfort with superior joint function. This data clearly identifies a clear need for further studies to identify the cell and molecular biological and other basis for these differences and be able to utilize this information for stratification in order to improve outcome for both women and men.

Keywords: gender differences, micro-fragmented adipose tissue, knee osteoarthritis, stem cells

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Authors: S. Hussain, C. Grieco, M. Brosnan

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Background and Aims: Autism is a complex neurobehavioural disorder, characterised by impairments in the development of language and communication skills. The study involved a state-of-art systematic review, in addition to qualitative data analysis, to establish the evidence for social stories as an intervention strategy for autistic children. An up-to-date review of the use of digital technologies in the delivery of interventions to autistic children was also carried out; to propose the efficacy of digital technologies and the use of social stories to improve intervention outcomes for autistic children. Methods: Two student researchers reviewed a range of randomised control trials and observational studies. The aim of the review was to establish if there was adequate evidence to justify recommending social stories to autistic patients. Students devised their own search strategies to be used across a range of search engines, including Ovid-Medline, Google Scholar and PubMed. Students then critically appraised the generated literature. Additionally, qualitative data obtained from a comprehensive online questionnaire on social stories was also thematically analysed. The thematic analysis was carried out independently by each researcher, using a ‘bottom-up’ approach, meaning contributors read and analysed responses to questions and devised semantic themes from reading the responses to a given question. The researchers then placed each response into a semantic theme or sub-theme. The students then joined to discuss the merging of their theme headings. The Inter-rater reliability (IRR) was calculated before and after theme headings were merged, giving IRR for pre- and post-discussion. Lastly, the thematic analysis was assessed by a third researcher, who is a professor of psychology and the director for the ‘Centre for Applied Autism Research’ at the University of Bath. Results: A review of the literature, as well as thematic analysis of qualitative data found supporting evidence for social story use. The thematic analysis uncovered some interesting themes from the questionnaire responses, relating to the reasons why social stories were used and the factors influencing their effectiveness in each case. However, overall, the evidence for digital technologies interventions was limited, and the literature could not prove a causal link between better intervention outcomes for autistic children and the use of technologies. However, they did offer valid proposed theories for the suitability of digital technologies for autistic children. Conclusions: Overall, the review concluded that there was adequate evidence to justify advising the use of social stories with autistic children. The role of digital technologies is clearly a fast-emerging field and appears to be a promising method of intervention for autistic children; however, it should not yet be considered an evidence-based approach. The students, using this research, developed ideas on social story interventions which aim to help autistic children.

Keywords: autistic children, digital technologies, intervention, social stories

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Authors: Keenoo Bibi Sumera, Alsheikh Mona, Mubarak Jan Beebee Zeba Mahetaab

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Background: Due to the busy schedule of the practicing clinicians at the hospitals, students may not always be attended to, which is to their detriment. The clinicians at the hospitals are also not always acquainted with teaching and/or supervising students on their placements. Additionally, there is a high student-patient ratio. Since they are the prospective clinical doctors under training, they need to reach the competence levels in clinical decision-making skills to be able to serve the healthcare system of the country and to be safe doctors. Aims and Objectives: A reflective portfolio was used to provide a means for students to learn by reflecting on their experiences and obtaining continuous feedback. This practice is an attempt to compensate for the scarcity of lack of resources, that is, clinical placement supervisors and patients. It is also anticipated that it will provide learners with a continuous monitoring and learning gap analysis tool for their clinical skills. Methodology: A hardcopy reflective portfolio was designed and validated. The portfolio incorporated a mini clinical evaluation exercise (mini-CEX), direct observation of procedural skills and reflection sections. Workshops were organized for the stakeholders, that is the management, faculty and students, separately. The rationale of reflection was emphasized. Students were given samples of reflective writing. The portfolio was then implemented amongst the undergraduate medical students of years four, five and six during clinical clerkship. After 16 weeks of implementation of the portfolio, a survey questionnaire was introduced to explore how undergraduate students perceive the educational value of the reflective portfolio and its impact on their deep information processing. Results: The majority of the respondents are in MD Year 5. Out of 52 respondents, 57.7% were doing the internal medicine clinical placement rotation, and 42.3% were in Otorhinolaryngology clinical placement rotation. The respondents believe that the implementation of a reflective portfolio helped them identify their weaknesses, gain professional development in terms of helping them to identify areas where the knowledge is good, increase the learning value if it is used as a formative assessment, try to relate to different courses and in improving their professional skills. However, it is not necessary that the portfolio will improve the self-esteem of respondents or help in developing their critical thinking, The portfolio takes time to complete, and the supervisors are not useful. They had to chase supervisors for feedback. 53.8% of the respondents followed the Gibbs reflective model to write the reflection, whilst the others did not follow any guidelines to write the reflection 48.1% said that the feedback was helpful, 17.3% preferred the use of written feedback, whilst 11.5% preferred oral feedback. Most of them suggested more frequent feedback. 59.6% of respondents found the current portfolio user-friendly, and 28.8% thought it was too bulky. 27.5% have mentioned that for a mobile application. Conclusion: The reflective portfolio, through the reflection of their work and regular feedback from supervisors, has an overall positive impact on the learning process of undergraduate medical students during their clinical clerkship.

Keywords: Portfolio, Reflection, Feedback, Clinical Placement, Undergraduate Medical Education

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Authors: Christina Klippel, Lucia Pezzi, Silvio Neto, Rafael Bertani, Priscila Mendes, Flavio Machado, Aline Szeliga, Maria Cosendey, Adilson Mariz, Raquel Santos, Lys Bendett, Pedro Velasco, Thalita Rolleigh, Bruna Bellote, Daria Coelho, Bruna Martins, Julia Almeida, Juliana Cerqueira

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This project presents a framework for teaching intracranial pressure monitoring (ICP) concepts using a low-cost experimental model in a neurointensive care education program. Data concerning ICP monitoring contribute to the patient's clinical assessment and may dictate the course of action of a health team (nursing, medical staff) and influence decisions to determine the appropriate intervention. This study aims to present a safe method for teaching ICP monitoring to medical students in a Simulation Center. Methodology: Medical school teachers, along with students from the 4th year, built an experimental model for teaching ICP measurement. The model consists of a mannequin's head with a plastic bag inside simulating the cerebral ventricle and an inserted ventricular catheter connected to the ICP monitoring system. The bag simulating the ventricle can also be changed for others containing bloody or infected simulated cerebrospinal fluid. On the mannequin's ear, there is a blue point indicating the right place to set the "zero point" for accurate pressure reading. The educational program includes four steps: 1st - Students receive a script on ICP measurement for reading before training; 2nd - Students watch a video about the subject created in the Simulation Center demonstrating each step of the ICP monitoring and the proper care, such as: correct positioning of the patient, anatomical structures to establish the zero point for ICP measurement and a secure range of ICP; 3rd - Students train the procedure in the model. Teachers help students during training; 4th - Student assessment based on a checklist form. Feedback and correction of wrong actions. Results: Students expressed interest in learning ICP monitoring. Tests concerning the hit rate are still being performed. ICP's final results and video will be shown at the event. Conclusion: The study of intracranial pressure measurement based on an experimental model consists of an effective and controlled method of learning and research, more appropriate for teaching neurointensive care practices. Assessment based on a checklist form helps teachers keep track of student learning progress. This project offers medical students a safe method to develop intensive neurological monitoring skills for clinical assessment of patients with neurological disorders.

Keywords: neurology, intracranial pressure, medical education, simulation

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Authors: Vishnu Emani, Andreas Escher, Ellen Roche

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Background: Orthostatic hypotension (OH) is an autonomic disorder marked by a sudden drop in blood pressure upon standing resulting from autonomic dysfunction. OH is especially prevalent in elderly populations, affecting more than 30% of Americans over the age of 70. OH is one of the most significant risk factors for accidental falls in elderly populations, making it a crucial focus for medical and device therapies. Pharmacologic therapy with midodrine and fludrocortisone may alleviate hypotension but have significant adverse side effects. Abdominal passive compression devices (binders) are more effective than lower extremity compression stockings at mitigating postural hypotension, by improving venous return to the heart. However, abdominal binders are difficult to don and uncomfortable to wear, leading to poor compliance. A disadvantage of passive compression devices is their inability to selectively compress during the crucial moment of standing. it have recently developed an active compression device that applies external pressure on the abdomen during transition from prone to supine position and conducted initial prototype testing. Methods: An active abdominal compression device was developed utilizing a simple, servo-driven strap-tightening mechanism to supply tension onto foam fabric, which applies pressure to the abdomen. Healthy volunteers (n=5) were utilized for prototype testing and were subjected to three conditions: no compression, passive compression (i.e. standard abdominal binder), and active compression (device prototype). Abdominal applied pressure during device activation was measured by strain-gauge manometer placed between the skin and binder. Systolic (SBP) and mean (MAP) arterial blood pressure was measured by standard blood pressure cuff in supine position followed by repeat measurements at 1 minute intervals for 5 minutes following upright position. A survey tool was administered to determine scores (1-10) for comfort and ease of donning abdominal binders. Results: Abdominal pressure increased from 0 to 15±3 mmHg upon device activation for both passive and active compression devices. During transition from supine to upright position, both active and passive compression devices demonstrated significantly higher MAP compared to the no-compression condition (67±4, 68±5, 62±5 respectively P<0.05), but there was no statistically significant difference in SBP or MAP when comparing active to passive compression. Active compression demonstrated significantly higher comfort scores (8.3±1) compared to passive compression (3.2±2) but lower when compared to no compression (10). Subjects universally reported that active compression device was easier to don compared to passive device. Conclusions: Active or passive abdominal compression prevents hypotension associated with postural changes. Active compression is associated with increased comfort and ease of donning compared to passive compression devices. Future trials are warranted to investigate the efficacy of our device in patients with OH.

Keywords: orthostatic hypotension, compression binder, abdominal binder, active abdominal compression

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Authors: Ella Abaev, Shany Segal, Miri Gabay

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Background: Choking is a blockage of airways that prevents efficient breathing and air flow to the lungs. Choking may be partial or full and is an emergency situation. Complete or prolonged choking leads to apnea, lack of oxygen in the tissues of the body and brain, and can cause death. There are three mechanisms of choking: obstruction of internal respiratory tracts by food or object aspiration, any material that blocks or covers external air passages, external pressure on the neck or trapping between objects. Children's airways are narrower than that of adults and therefore the risk of choking is greater, due to the aspiration of food and other foreign bodies into the lungs. In the Child Development Center at Safra Children’s Hospital, Tel Hashomer in Israel are treated infants, toddlers, and children aged 0-18 years with various developmental disabilities. Due to the increase in reports of ‘almost an event’ of choking in the past year and the serious consequences of choking event, it was decided to give an emphasis to the issue. Incidence and methods: The number of reports of ‘almost an event’ or a choking event was examined at the center during the years 2013-2018 and a thorough research work was conducted on the subject in order to build a prevention program. Findings: Between 2013 and 2018 the center reported about ten cases of ‘almost choking events’. In the middle of 2018 alone three cases of ‘almost an event’ were reported. Objective: Providing knowledge leads to awareness raise, change of perception, change in behavior and prevention. The center employs more than 130 staff members from various sectors so that it is the work of multi-professional teams to promote the quality and safety of the treatment. The familiarity of the staff with risk factors, prevention guidelines, identification of choking signs, and treatment are most important and significant in determining the outcome of a choking event. Conclusions and recommendations: After in-depth research work was carried out in cooperation with the Risk Management Unit on the subject of choking, which include a description of the definitions, mechanisms, risk factors, treatment methods and extensive recommendations for prevention (e.g. using treatment and stimulation accessories with standards association stamps and adjustment of the type of food and the way it is served to match to the child's age and the ability to swallow). The expected stages of development and emphasis on the population of children with special needs were taken into account. The research findings will be published by the staff and parents of the patients, professional publications, and lectures and there is an expectation to decrease the number of choking events in the next years.

Keywords: children with special needs, choking, educational system, prevention guidelines

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Authors: Sadeem Aljamaan, Reem Hariri, Rahaf Alghamdi, Batool Alotaibi, Batool Alsenan, Lama Althunayyan, Areej Alnemer

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The aim of this study is to correlate between radiological findings and histopathological results in regard to the breast imaging-reporting and data system scores, size of breast masses, molecular subtypes and suspicious radiological features, as well as to assess the concordance rate in histological grade between core biopsy and surgical excision among breast cancer patients, followed by analyzing the change of concordance rate in relation to neoadjuvant chemotherapy in a Saudi population. A retrospective review was conducted over 6-year period (2017-2022) on all breast core biopsies of women preceded by radiological investigation. Chi-squared test (χ2) was performed on qualitative data, the Mann-Whitney test for quantitative non-parametric variables, and the Kappa test for grade agreement. A total of 641 cases were included. Ultrasound, mammography, and magnetic resonance imaging demonstrated diagnostic accuracies of 85%, 77.9% and 86.9%; respectively. magnetic resonance imaging manifested the highest sensitivity (72.2%), and the lowest was for ultrasound (61%). Concordance in tumor size with final excisions was best in magnetic resonance imaging, while mammography demonstrated a higher tendency of overestimation (41.9%), and ultrasound showed the highest underestimation (67.7%). The association between basal-like molecular subtypes and the breast imaging-reporting and data system score 5 classifications was statistically significant only for magnetic resonance imaging (p=0.04). Luminal subtypes demonstrated a significantly higher percentage of speculation in mammography. Breast imaging-reporting and data system score 4 manifested a substantial number of benign pathologies in all the 3 modalities. A fair concordance rate (k= 0.212 & 0.379) was demonstrated between excision and the preceding core biopsy grading with and without neoadjuvant therapy, respectively. The results demonstrated a down-grading in cases post-neoadjuvant therapy. In cases who did not receive neoadjuvant therapy, underestimation of tumor grade in biopsy was evident. In summary, magnetic resonance imaging had the highest sensitivity, specificity, positive predictive value and accuracy of both diagnosis and estimation of tumor size. Mammography demonstrated better sensitivity than ultrasound and had the highest negative predictive value, but ultrasound had better specificity, positive predictive value and accuracy. Therefore, the combination of different modalities is advantageous. The concordance rate of core biopsy grading with excision was not impacted by neoadjuvant therapy.

Keywords: breast cancer, mammography, MRI, neoadjuvant, pathology, US

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Authors: S. Hatamikia, A. Biguri, H. Furtado, G. Kronreif, J. Kettenbach, W. Birkfellner

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Nowadays, three dimensional Cone Beam CT (CBCT) has turned into a widespread clinical routine imaging modality for interventional radiology. In conventional CBCT, a circular sourcedetector trajectory is used to acquire a high number of 2D projections in order to reconstruct a 3D volume. However, the accumulated radiation dose due to the repetitive use of CBCT needed for the intraoperative procedure as well as daily pretreatment patient alignment for radiotherapy has become a concern. It is of great importance for both health care providers and patients to decrease the amount of radiation dose required for these interventional images. Thus, it is desirable to find some optimized source-detector trajectories with the reduced number of projections which could therefore lead to dose reduction. In this study we investigate some source-detector trajectories with the optimal arbitrary orientation in the way to maximize performance of the reconstructed image at particular regions of interest. To achieve this approach, we developed a box phantom consisting several small target polytetrafluoroethylene spheres at regular distances through the entire phantom. Each of these spheres serves as a target inside a particular region of interest. We use the 3D Point Spread Function (PSF) as a measure to evaluate the performance of the reconstructed image. We measured the spatial variance in terms of Full-Width-Half-Maximum (FWHM) of the local PSFs each related to a particular target. The lower value of FWHM shows the better spatial resolution of reconstruction results at the target area. One important feature of interventional radiology is that we have very well-known imaging targets as a prior knowledge of patient anatomy (e.g. preoperative CT) is usually available for interventional imaging. Therefore, we use a CT scan from the box phantom as the prior knowledge and consider that as the digital phantom in our simulations to find the optimal trajectory for a specific target. Based on the simulation phase we have the optimal trajectory which can be then applied on the device in real situation. We consider a Philips Allura FD20 Xper C-arm geometry to perform the simulations and real data acquisition. Our experimental results based on both simulation and real data show our proposed optimization scheme has the capacity to find optimized trajectories with minimal number of projections in order to localize the targets. Our results show the proposed optimized trajectories are able to localize the targets as good as a standard circular trajectory while using just 1/3 number of projections. Conclusion: We demonstrate that applying a minimal dedicated set of projections with optimized orientations is sufficient to localize targets, may minimize radiation.

Keywords: CBCT, C-arm, reconstruction, trajectory optimization

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Authors: Mariana Branco, Nahida Sobrino, Cristina Neves, Márcia Santos, Afonso Granja, João Rosa Oliveira, Joana Costa, Luísa Castro Leite

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This case reports a COVID-19 infection in an unvaccinated adult man with no history of COVID-19 and no relevant clinical history besides anabolic steroid use, undergoing weaning with tamoxifen after a bodybuilding competition. The patient presented a 4cm cervical mass 3 weeks after COVID-19 infection in his cohabitants. He was otherwise asymptomatic and tested negative to multiple RT-PCR tests. Nevertheless, the IgG COVID-19 antibody was positive, suggesting the previous infection. This report raises a potential link between anabolic steroid use and atypical COVID-19 onset. Objectives: The goals of this paper are to raise a potential link between anabolic steroid use and atypical COVID-19 onset but also to report an uncommon case of COVID-19 infection with consecutive negative gold standard tests. Methodology: The authors used CARE guidelines for case report writing. Introduction: This case reports a COVID-19 infection case in an unvaccinated adult man, with multiple serial negative reverse transcription polymerase chain reaction (RT-PCR) test results, presenting with single cervical lymphadenopathy. Although the association between COVID-19 and lymphadenopathy is well established, there are no cases with this presentation, and consistently negative RT-PCR tests have been reported. Methodologies: The authors used CARE guidelines for case report writing. Case presentation: This case reports a 28-year-old Caucasian man with no previous history of COVID-19 infection or vaccination and no relevant clinical history besides anabolic steroid use undergoing weaning with tamoxifendue to participation in a bodybuilding competition. He visits his primary care physician because of a large (4 cm) cervical lump, present for 3 days prior to the consultation. There was a positive family history for COVID-19 infection 3 weeks prior to the visit, during which the patient cohabited with the infected family members. The patient never had any previous clinical manifestation of COVID-19 infection and, despite multiple consecutive RT-PCR testing, never tested positive. The patient was treated with an NSAID and a broad-spectrum antibiotic, with little to no effect. Imagiological testing was performed via a cervical ultrasound, followed by a needle biopsy for histologic analysis. Serologic testing for COVID-19 immunity was conducted, revealing a positive Anti-SARS-CoV-2 IgG (Spike S1) antibody, suggesting the previous infection, given the unvaccinated status of our patient Conclusion: In patients with a positive epidemiologic context and cervical lymphadenopathy, physicians should still consider COVID-19 infection as a differential diagnosis, despite negative PCR testing. This case also raises a potential link between anabolic steroid use and atypical COVID-19 onset, never before reported in scientific literature.

Keywords: COVID-19, cervical lymphadenopathy, anabolic steroids, primary care

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Authors: Yasinta Ratna Esti Wulandari, Vivitri Dewi Prasasty, Adrianus Rio, Cindy Geniola

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Mulberry is a plant that widely cultivated around the world, mostly for silk industry. In recent years, the study showed that the mulberry leaves have an anti-diabetic effect which mostly comes from the compound known as 1-deoxynojirimycin (DNJ). DNJ is a very potent α-glucosidase inhibitor. It will decrease the degradation rate of carbohydrates in digestive tract, leading to slower glucose absorption and reducing the post-prandial glucose level significantly. The mulberry leaves also known as the best source of DNJ. Since then, the DNJ in mulberry leaves had received a considerable attention, because of the increased number of diabetic patients and the raise of people awareness to find a more natural cure for diabetic. The DNJ content in mulberry leaves varied depend on the mulberry species, leaf’s age, and the plant’s growth environment. Few of the mulberry varieties that were cultivated in Indonesiaare Morus alba var. kanva-2, M. alba var. multicaulis, M. bombycis var. lembang, and M. cathayana. The lack of data concerning phytochemicals contained in the Indonesian mulberry leaves are restraining their use in the medicinal field. The aim of this study is to fully utilize the use of mulberry leaves cultivated in Indonesia as a medicinal herb in local, national, or global community, by determining the DNJ and other phytochemical contents in them. This study used eight leaf samples which are the young leaves and mature leaves of both Morus alba var. kanva-2, M. alba var. multicaulis, M. bombycis var. lembang, and M. cathayana. The DNJ content was analyzed using reverse phase high performance liquid chromatography (HPLC). The stationary phase was silica C18 column and the mobile phase was acetonitrile:acetic acid 0.1% 1:1 with elution rate 1 mL/min. Prior to HPLC analysis the samples were derivatized with FMOC to ensure the DNJ detectable by VWD detector at 254 nm. Results showed that the DNJ content in samples are ranging from 2.90-0.07 mg DNJ/ g leaves, with the highest content found in M. cathayana mature leaves (2.90 ± 0.57 mg DNJ/g leaves). All of the mature leaf samples also found to contain higher amount of DNJ from their respective young leaf samples. The phytochemicals in leaf samples was tested using qualitative test. Result showed that all of the eight leaf samples contain alkaloids, phenolics, flavonoids, tannins, and terpenes. The presence of this phytochemicals contribute to the therapeutic effect of mulberry leaves. The pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS) analysis was also performed to the eight samples to quantitatively determine their phytochemicals content. The pyrolysis temperature was set at 400 °C, with capillary column Phase Rtx-5MS 60 × 0.25 mm ID stationary phase and helium gas mobile phase. Few of the terpenes found are known to have anticancer and antimicrobial properties. From all the results, all of four samples of mulberry leaves which are cultivated in Indonesia contain DNJ and various phytochemicals like alkaloids, phenolics, flavonoids, tannins, and terpenes which are beneficial to our health.

Keywords: Morus, 1-deoxynojirimycin, HPLC, Py-GC-MS

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Authors: Sthephanie A. Colmenares, Fabio A. Rojas, Pablo A. Arbeláez, Johann F. Osma, Diana Narvaez

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The loss of functional tissue is a ubiquitous and expensive health care problem, with very limited treatment options for these patients. The golden standard for large bone damage is a cadaveric bone as an allograft with stainless steel support; however, this solution only applies to bones with simple morphologies (long bones), has a limited material supply and presents long term problems regarding mechanical strength, integration, differentiation and induction of native bone tissue. Therefore, the fabrication of a scaffold with biological, physical and chemical properties similar to the human bone with a fabrication method for morphology manipulation is the focus of this investigation. Towards this goal, an alginate and coral matrix was created using two production techniques; the coral was chosen because of its chemical composition and the alginate due to its compatibility and mechanical properties. In order to construct the coral alginate scaffold the following methodology was employed; cleaning of the coral, its pulverization, scaffold fabrication and finally the mechanical and biological characterization. The experimental design had: mill method and proportion of alginate and coral, as the two factors, with two and three levels each, using 5 replicates. The coral was cleaned with sodium hypochlorite and hydrogen peroxide in an ultrasonic bath. Then, it was milled with both a horizontal and a ball mill in order to evaluate the morphology of the particles obtained. After this, using a combination of alginate and coral powder and water as a binder, scaffolds of 1cm3 were printed with a SpectrumTM Z510 3D printer. This resulted in solid cubes that were resistant to small compression stress. Then, using a ESQUIM DP-143 silicon mold, constructs used for the mechanical and biological assays were made. An INSTRON 2267® was implemented for the compression tests; the density and porosity were calculated with an analytical balance and the biological tests were performed using cell cultures with VERO fibroblast, and Scanning Electron Microscope (SEM) as visualization tool. The Young’s moduli were dependent of the pulverization method, the proportion of coral and alginate and the interaction between these factors. The maximum value was 5,4MPa for the 50/50 proportion of alginate and horizontally milled coral. The biological assay showed more extracellular matrix in the scaffolds consisting of more alginate and less coral. The density and porosity were proportional to the amount of coral in the powder mix. These results showed that this composite has potential as a biomaterial, but its behavior is elastic with a small Young’s Modulus, which leads to the conclusion that the application may not be for long bones but for tissues similar to cartilage.

Keywords: alginate, biomaterial, bone engineering, coral, Porites asteroids, SEM

Procedia PDF Downloads 254

Authors: Aakriti Chetan Shah, Elle Sein

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Background/purpose: Group B Streptococcus(GBS) is the leading cause of severe early onset infection in newborns, with the incidence of Early Onset Group B Streptococcus (EOGBS) in the UK and Ireland rising from 0.48 to 0.57 per 1000 births from 2000 to 2015. A WHO study conducted in 2017, has shown that 38.5% of cases can result in stillbirth and infant deaths. This is an important problem to consider as 20% of women worldwide have GBS colonisation and can suffer from these detrimental effects. Current Royal College of Obstetricians and Midwives (RCOG) guidelines do not recommend bacteriological screening for pregnant women due to its low sensitivity in antenatal screening correlating with the neonate having GBS but advise a patient information leaflet be given to pregnant women. However, a Healthcare Safety Investigation Branch (HSIB) 2019 learning report found that only 50% of trusts and health boards reported giving GBS information leaflets to all pregnant mothers. Therefore, this audit aimed to assess current practices of information dissemination about GBS at Chelsea & Westminster (C&W) Hospital. Methodology: A quantitative cross-sectional study was carried out using a questionnaire based on the RCOG GBS guidelines and the HSIB Learning report. The study was conducted in antenatal clinics at Chelsea & Westminster Hospital, from 29th January 2021 to 14th February 2021, with twenty-two practicing obstetricians and midwives participating in the survey. The main outcome measure was the proportion of obstetricians and midwives who disseminate information about GBS to pregnant women, and the reasons behind why they do or do not. Results: 22 obstetricians and midwives responded with 18 complete responses. Of which 12 were obstetricians and 6 were midwives. Only 17% of clinical staff routinely inform all pregnant women about GBS, and do so at varying timeframes of the pregnancy, with an equal split in the first, second and third trimester. The primary reason for not informing women about GBS was influenced by three key factors: Deemed relevant only for patients at high risk of GBS, lack of time in clinic appointments and no routine NHS screening available. Interestingly 58% of staff in the antenatal clinic believe it is necessary to inform all women about GBS and its importance. Conclusion: It is vital for obstetricians and midwives to inform all pregnant women about GBS due to the high prevalence of incidental carriers in the population, and the harmful effects it can cause for neonates. Even though most clinicians believe it is important to inform all pregnant women about GBS, most do not. To ensure that RCOG and HSIB recommendations are followed, we recommend that women should be given this information at 28 weeks gestation in the antenatal clinic. Proposed implementations include an information leaflet to be incorporated into the Mum and Baby app, an informative video and end-to-end digital clinic documentation to include this information sharing prompt.

Keywords: group B Streptococcus, early onset sepsis, Antenatal care, Neonatal morbidity, GBS

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Authors: Mustafa M. Donma, Orkide Donma

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Spexin, expressed in central nervous system, has attracted much interest in feeding behavior, obesity, diabetes, energy metabolism and cardiovascular functions. Fetuin A is known as negative acute phase reactant synthesized in the liver. So far, it has become a major concern of many studies in numerous clinical states. The relationship between the concentrations of spexin as well as fetuin A and the risk for cardiovascular diseases (CVDs) were also investigated. Eosinophils, suggested to be associated with the development of CVDs, are introduced as early indicators of cardiometabolic complications. Patients with elevated platelet count, associated with hypercoagulable state in the body, are also more liable to CVDs. In this study, the aim is to examine the profiles of spexin and fetuin A concomitant with the course of variations detected in eosinophil as well as platelet counts in morbid obese children. Thirty-four children with normal-body mass index (N-BMI) and fifty-one morbid obese (MO) children participated in the study. Written-informed consent forms were obtained prior to the study. Institutional ethics committee approved the study protocol. Age- and sex-adjusted BMI percentile tables prepared by World Health Organization were used to classify healthy and obese children. Mean age ± SEM of the children were 9.3 ± 0.6 years and 10.7 ± 0.5 years in N-BMI and MO groups, respectively. Anthropometric measurements of the children were taken. Body mass index values were calculated from weight and height values. Blood samples were obtained after an overnight fasting. Routine hematologic and biochemical tests were performed. Within this context, fasting blood glucose (FBG), insulin (INS), triglycerides (TRG), high density lipoprotein-cholesterol (HDL-C) concentrations were measured. Homeostatic model assessment for insulin resistance (HOMA-IR) values were calculated. Spexin and fetuin A levels were determined by enzyme-linked immunosorbent assay. Data were evaluated from the statistical point of view. Statistically significant differences were found between groups in terms of BMI, fat mass index, INS, HOMA-IR and HDL-C. In MO group, all parameters increased as HDL-C decreased. Elevated concentrations in MO group were detected in eosinophils (p<0.05) and platelets (p>0.05). Fetuin A levels decreased in MO group (p>0.05). However, decrease was statistically significant in spexin levels for this group (p<0.05). In conclusion, these results have suggested that increases in eosinophils and platelets exhibit behavior as cardiovascular risk factors. Decreased fetuin A behaved as a risk factor suitable to increased risk for cardiovascular problems associated with the severity of obesity. Along with increased eosinophils, increased platelets and decreased fetuin A, decreased spexin was the parameter, which reflects best its possible participation in the early development of CVD risk in MO children.

Keywords: cardiovascular diseases , eosinophils , fetuin A , pediatric morbid obesity , platelets , spexin

Procedia PDF Downloads 193

Authors: Apurva Singh, S. P. Jaiswar, Apala Priyadarshini, Akancha Pandey

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Objective: The aim of this study is to find the association of PON1 gene polymorphism with pesticides In RPL subjects. Background: Recurrent pregnancy loss (RPL) is defined as three or more sequential abortions before the 20th week of gestation. Pesticides and its derivatives (organochlorine and organophosphate) are proposed to accommodate a ruler chemical for RPL in the sub-humid region of India. The paraoxonase-1 enzyme (PON1) plays an important role in the toxicity of some organophosphate pesticides, with low PON1 activity being associated with higher pesticide sensitivity Methodology: This is a case-control study done in Department of Obstetrics & Gynaecology & Department of Biochemistry, K.G.M.U, Lucknow, India. The subjects were enrolled after fulfilling the inclusion & exclusion criteria. Inclusion criteria: Cases- Subject having two or more spontaneous abortions & Control- Healthy female having one or more alive child was selected. Exclusion criteria: Cases & Control- Subject having the following disease will be excluded from the study Diabetes mellitus, Hypertension, Tuberculosis, Immunocompromised patients, any endocrine disorder and genital, colon or breast cancer any other malignancies. Blood samples were collected in EDTA tubes from cases & healthy control women & genomic DNA was extracted by phenol-chloroform method. The estimation of pesticides residue from blood was done by HPLC. Biochemical estimation was also performed. Genotyping of PON1 gene polymorphism was performed by RFLP. Statistical analysis of the data was performed using the SPSS16.3 software. Results: A sum of total 14 pesticides (12 organochlorine and 2 organophosphate) selected on the basis of their persistent nature and consumption rate. The significant level of pesticide (ppb) estimated by the Mann whiney test and it was found to be significant at higher level of β-HCH (p:0.04), γ-HCH (p:0.001), δ-HCH (p: 0.002), chloropyrifos (p:0.001), pp-DDD (p:0.001) and fenvalrate (p: 0.001) in case group compare to its control. The level of antioxidant enzymes were found to be significantly decreased among the cases. Wild homozygous TT was more frequent and prevalent among control groups. However, heterozygous group (Tt) was more in cases than control groups (CI-0.3-1.3) (p=0.06). Conclusion: Higher levels of pesticides with endocrine disrupting potential in cases indicate the possible role of these compounds as one of the causes of recurrent pregnancy loss. Possibly, increased pesticide level appears to indicate increased levels of oxidative damage that has been associated with the possible cause of Recurrent Miscarriage, it may reflect indirect evidence of toxicity rather than the direct cause. Since both factors are reported to increase risk, individuals with higher levels of these 'Toxic compounds' especially in 'high-risk genotypes' might be more susceptible to recurrent pregnancy loss.

Keywords: paraoxonase, pesticides, PON1, RPL

Procedia PDF Downloads 143

Authors: Su Hui Tsai, Weir Sen Lin, Rhay Hung Weng

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There are numerous outpatient departments at hospitals with enormous amounts of outpatients. Although the work of outpatient nursing staff does not include the ward, emergency and critical care units that involve patient life-threatening conditions, the work is cumbersome and requires facing and dealing with a large number of outpatients in a short period of time. Therefore, nursing staff often do not feel satisfied with their work and cannot identify with their professional role, leading to intentions to leave their job. Thus, the main purpose of this study is to explore the correlation between the job satisfaction and role identity of nursing staff with turnover intention. This research was conducted using a questionnaire, and the subjects were outpatient nursing staff in three regional hospitals in Southern Taiwan. A total of 175 questionnaires were distributed, and 166 valid questionnaires were returned. After collecting the data, the reliability and validity of the study variables were confirmed by confirmatory factor analysis. The influence of role identity and job satisfaction on nursing staff’s turnover intention was analyzed by descriptive analysis, one-way ANOVA, Pearson correlation analysis and multiple regression analysis. Results showed that 'role identity' had significant differences in different types of marriages. Job satisfaction of 'grasp of environment' had significant differences in different levels of education. Job satisfaction of 'professional growth' and 'shifts and days off' showed significant differences in different types of marriages. 'Role identity' and 'job satisfaction' were negatively correlated with turnover intention respectively. Job satisfaction of 'salary and benefits' and 'grasp of environment' were significant predictors of role identity. The higher the job satisfaction of 'salary and benefits' and 'grasp of environment', the higher the role identity. Job satisfaction of 'patient and family interaction' were significant predictors of turnover intention. The lower the job satisfaction of 'patient and family interaction', the higher the turnover intention. This study found that outpatient nursing staff had the lowest satisfaction towards salary structure. It is recommended that bonuses, promotion opportunities and other incentives be established to increase the role identity of outpatient nursing staff. The results showed that the higher the job satisfaction of 'salary and benefits' and 'grasp of environment', the higher the role identity. It is recommended that regular evaluations be conducted to reward nursing staff with excellent service and invite nursing staff to share their work experiences and thoughts, to enhance nursing staff’s expectation and identification of their occupational role, as well as instilling the concept of organizational service and organizational expectations of emotional display. The results showed that the lower the job satisfaction of 'patient and family interaction', the higher the turnover intention. It is recommended that interpersonal communication and workplace violence prevention educational training courses be organized to enhance the communication and interaction of nursing staff with patients and their families.

Keywords: outpatient, job satisfaction, turnover, intention

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Authors: Spira A., Marabelle A., Kientop D., Moser E., Mumm J.

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Background: Both interleukin-2 (IL-2) and interleukin-10 (IL-10) have been extensively studied for their stimulatory function on T cells and their potential to obtain sustainable tumor control in RCC, melanoma, lung, and pancreatic cancer as monotherapy, as well as combination with PD-1 blockers, radiation, and chemotherapy. While approved, IL-2 retains significant toxicity, preventing its widespread use. The significant efforts undertaken to uncouple IL-2 toxicity from its anti-tumor function have been unsuccessful, and early phase clinical safety observed with PEGylated IL-10 was not met in a blinded Phase 3 trial. Deka Biosciences has engineered a novel molecule coupling wild-type IL-2 to a high affinity variant of Epstein Barr Viral (EBV) IL-10 via a scaffold (scFv) that binds to epidermal growth factor receptors (EGFR). This patented molecule, termed DK210 (EGFR), is retained at high levels within the tumor microenvironment for days after dosing. In addition to overlapping and non-redundant anti-tumor function, IL-10 reduces IL-2 mediated cytokine release syndrome risks and inhibits IL-2 mediated T regulatory cell proliferation. Methods: DK210 (EGFR) is being evaluated in an open-label, dose-escalation (Phase 1) study with 5 (0.025-0.3 mg/kg) monotherapy dose levels and (expansion cohorts) in combination with PD-1 blockers, or radiation or chemotherapy in patients with advanced solid tumors overexpressing EGFR. Key eligibility criteria include 1) confirmed progressive disease on at least one line of systemic treatment, 2) EGFR overexpression or amplification documented in histology reports, 3) at least a 4 week or 5 half-lives window since last treatment, and 4) excluding subjects with long QT syndrome, multiple myeloma, multiple sclerosis, myasthenia gravis or uncontrolled infectious, psychiatric, neurologic, or cancer disease. Plasma and tissue samples will be investigated for pharmacodynamic and predictive biomarkers and genetic signatures associated with IFN-gamma secretion, aiming to select subjects for treatment in Phase 2. Conclusion: Through successful coupling of wild-type IL-2 with a high affinity IL-10 and targeting directly to the tumor microenvironment, DK210 (EGFR) has the potential to harness IL-2 and IL-10’s known anti-cancer promise while reducing immunogenicity and toxicity risks enabling safe concomitant cytokine treatment with other anti-cancer modalities.

Keywords: cytokine, EGFR over expression, interleukine-2, interleukine-10, clinical trial

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Authors: Christine P. Gibson, Ramona Alex, Michael Farney, Johana Vallejo-Elias, Mitra Esfandiarei

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Aortic aneurysm is the leading cause of death in Marfan syndrome (MFS), a connective tissue disorder caused by mutations in fibrillin-1 gene (FBN1). MFS aneurysm is characterized by weakening of the aortic wall due to elastin fibers fragmentation and disorganization. The above-average height and distinct physical features make young adults with MFS desirable candidates for competitive sports; but little is known about the exercise limit at which they will be at risk for aortic rupture. On the other hand, aerobic cardiovascular exercise has been shown to have protective effects on the heart and aorta. We have previously reported that mild aerobic exercise can delay the formation of aortic aneurysm in a mouse model of MFS. In this study, we aimed to investigate the effects of various levels of exercise intensity on the progression of aortic aneurysm in the mouse model. Starting at 4 weeks of age, we subjected control and MFS mice to different levels of exercise intensity (8m/min, 10m/min, 15m/min, and 20m/min, corresponding to 55%, 65%, 75%, and 85% of VO2 max, respectively) on a treadmill for 30 minutes per day, five days a week for the duration of the study. At 24 weeks of age, aortic tissue were isolated and subjected to structural and functional studies using histology and wire myography in order to evaluate the effects of different exercise routines on elastin fragmentation and organization and aortic wall elasticity/stiffness. Our data shows that exercise training at the intensity levels between 55%-75% significantly reduces elastin fragmentation and disorganization, with less recovery observed in 85% MFS group. The reversibility of elasticity was also significantly restored in MFS mice subjected to 55%-75% intensity; however, the recovery was less pronounced in MFS mice subjected to 85% intensity. Furthermore, our data shows that smooth muscle cells (SMCs) contractilion in response to vasoconstrictor agent phenylephrine (100nM) is significantly reduced in MFS aorta (54.84 ± 1.63 mN/mm2) as compared to control (95.85 ± 3.04 mN/mm2). At 55% of intensity, exercise did not rescue SMCs contraction (63.45 ± 1.70 mN/mm2), while at higher intensity levels, SMCs contraction in response to phenylephrine was restored to levels similar to control aorta [65% (81.88 ± 4.57 mN/mm2), 75% (86.22 ± 3.84 mN/mm2), and 85% (83.91 ± 5.42 mN/mm2)]. This study provides the first time evidence that high intensity exercise (e.g. 85%) may not provide the most beneficial effects on aortic function (vasoconstriction) and structure (elastin fragmentation, aortic wall elasticity) during the progression of aortic aneurysm in MFS mice. On the other hand, based on our observations, medium intensity exercise (e.g. 65%) seems to provide the utmost protective effects on aortic structure and function in MFS mice. These findings provide new insights into the potential capacity, in which MFS patients could participate in various aerobic exercise routines, especially in young adults affected by cardiovascular complications particularly aortic aneurysm. This work was funded by Midwestern University Research Fund.

Keywords: aerobic exercise, aortic aneurysm, aortic wall elasticity, elastin fragmentation, Marfan syndrome

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Authors: Yang Yang, Luciana Magalhães Rebelo Alencar, Martha Sahylí Ortega Pijeira, Beatriz da Silva Batista, Alefe Roger Silva França, Erick Rafael Dias Rates, Ruana Cardoso Lima, Sara Gemini-Piperni, Ralph Santos-Oliveira

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Radium-²²³ dichloride ([²²³Rₐ]RₐCl₂) is an alpha particle-emitting radiopharmaceutical currently approved for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease. [²²³Rₐ]RₐCl₂ is bone-seeking calcium mimetic that bonds into the newly formed bone stroma, especially osteoblastic or sclerotic metastases, killing the tumor cells by inducing DNA breaks in a potent and localized manner. Nonetheless, the successful therapy of osteosarcoma as primary bone tumors is still a challenge. Nanomicelles are colloidal nanosystems widely used in drug development to improve blood circulation time, bioavailability, and specificity of therapeutic agents, among other applications. In addition, the enhanced permeability and retention effect of the nanosystems, and the renal excretion of the nanomicelles reported in most cases so far, are very attractive to achieve selective and increased accumulation in tumor site as well as to increase the safety of [²²³Rₐ]RₐCl₂ in the clinical routine. In the present work, [²²³Rₐ]RₐCl₂ nanomicelles were produced, characterized, in vitro evaluated, and compared with pure [²²³Rₐ]RₐCl2 solution using SAOS2 osteosarcoma cells. The [²²³Rₐ]RₐCl₂ nanomicelles were prepared using the amphiphilic copolymer Pluronic F127. The dynamic light scattering analysis of freshly produced [²²³Rₐ]RₐCl₂ nanomicelles demonstrated a mean size of 129.4 nm with a polydispersity index (PDI) of 0.303. After one week stored in the refrigerator, the mean size of the [²²³Rₐ]RₐCl₂ nanomicelles increased to 169.4 with a PDI of 0.381. Atomic force microscopy analysis of [223Rₐ]RₐCl₂ nanomicelles exhibited spherical structures whose heights reach 1 µm, suggesting the filling of 127-Pluronic nanomicelles with [²²³Rₐ]RₐCl₂. The viability assay with [²²³Rₐ]RₐCl₂ nanomicelles displayed a dose-dependent response as it was observed using pure [²²³Rₐ]RₐCl2. However, at the same dose, [²²³Rₐ]RₐCl₂ nanomicelles were 20% higher efficient in killing SAOS2 cells when compared with pure [²²³Rₐ]RₐCl₂. These findings demonstrated the effectiveness of the nanosystem validating the application of nanotechnology in targeted alpha therapy with [²²³Ra]RₐCl₂. In addition, the [²²³Rₐ]RaCl₂nanomicelles may be decorated and incorporated with a great variety of agents and compounds (e.g., monoclonal antibodies, aptamers, peptides) to overcome the limited use of [²²³Ra]RₐCl₂.

Keywords: nanomicelles, osteosarcoma, radium dichloride, targeted alpha therapy

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Authors: Wu Liching

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Aim This case aims to discuss the pathogenesis, clinical manifestations and medical treatment of strokes caused by mitochondrial gene mutations. Methods Diagnosis of ischemic stroke caused by mitochondrial gene defect by means of "next-generation sequencing mitochondrial DNA gene variation detection", imaging examination, neurological examination, and medical history; this study took samples from the neurology ward of a medical center in northern Taiwan cases diagnosed with acute cerebral infarction as the research objects. Result This case is a 49-year-old married woman with a rare disease, mitochondrial gene mutation inducing ischemic stroke. She has severe hearing impairment and needs to use hearing aids, and has a history of diabetes. During the patient’s hospitalization, the blood test showed that serum Lactate: 7.72 mmol/L, Lactate (CSF) 5.9 mmol/L. Through the collection of relevant medical history, neurological evaluation showed changes in consciousness and cognition, slow response in language expression, and brain magnetic resonance imaging examination showed subacute bilateral temporal lobe infarction, which was an atypical type of stroke. The lineage DNA gene has m.3243A>G known pathogenic mutation point, and its heteroplasmic level is 24.6%. This pathogenic point is located in MITOMAP and recorded as Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) , Leigh Syndrome and other disease-related pathogenic loci, this mutation is located in ClinVar and recorded as Pathogenic (dbSNP: rs199474657), so it is diagnosed as a case of stroke caused by a rare disease mitochondrial gene mutation. After medical treatment, there was no more seizure during hospitalization. After interventional rehabilitation, the patient's limb weakness, poor language function, and cognitive impairment have all improved significantly. Conclusion Mitochondrial disorders can also be associated with abnormalities in psychological, neurological, cerebral cortical function, and autonomic functions, as well as problems with internal medical diseases. Therefore, the differential diagnoses cover a wide range and are not easy to be diagnosed. After neurological evaluation, medical history collection, imaging and rare disease serological examination, atypical ischemic stroke caused by rare mitochondrial gene mutation was diagnosed. We hope that through this case, the diagnosis of rare disease mitochondrial gene variation leading to cerebral infarction will be more familiar to clinical medical staff, and this case report may help to improve the clinical diagnosis and treatment for patients with similar clinical symptoms in the future.

Keywords: acute stroke, MELAS, lactic acidosis, mitochondrial disorders

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Authors: Ana Julia Acevedo Urquiaga, Jose A. Acevedo Suarez, Ana Julia Urquiaga Rodriguez, Neyfe Sablon Cossio

Abstract:

Despite the progress made in logistics and supply chains fields, it is unavoidable the development of business models that use efficiently information to facilitate the integrated logistics flows management between partners. Collaborative management is an important tool for materializing the cooperation between companies, as a way to achieve the supply chain efficiency and effectiveness. The first face of this research was a comprehensive analysis of the collaborative planning on the Cuban companies. It is evident that they have difficulties in supply chains planning where production, supplies and replenishment planning are independent tasks, as well as logistics and distribution operations. Large inventories generate serious financial and organizational problems for entities, demanding increasing levels of working capital that cannot be financed. Problems were found in the efficient application of Information and Communication Technology on business management. The general objective of this work is to develop a methodology that allows the deployment of a planning and control system in a coordinated way on the medicine’s logistics system in Cuba. To achieve these objectives, several mechanisms of supply chain coordination, mathematical programming models, and other management techniques were analyzed to meet the requirements of collaborative logistics management in Cuba. One of the findings is the practical and theoretical inadequacies of the studied models to solve the current situation of the Cuban logistics systems management. To contribute to the tactical-operative management of logistics, the Collaborative Logistics Flow Management Model (CLFMM) is proposed as a tool for the balance of cycles, capacities, and inventories, always to meet the final customers’ demands in correspondence with the service level expected by these. The CLFMM has as center the supply chain planning and control system as a unique information system, which acts on the processes network. The development of the model is based on the empirical methods of analysis-synthesis and the study cases. Other finding is the demonstration of the use of a single information system to support the supply chain logistics management, allows determining the deadlines and quantities required in each process. This ensures that medications are always available to patients and there are no faults that put the population's health at risk. The simulation of planning and control with the CLFMM in medicines such as dipyrone and chlordiazepoxide, during 5 months of 2017, permitted to take measures to adjust the logistic flow, eliminate delayed processes and avoid shortages of the medicines studied. As a result, the logistics cycle efficiency can be increased to 91%, the inventory rotation would increase, and this results in a release of financial resources.

Keywords: collaborative management, medicine logistic system, supply chain planning, tactical-operative planning

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Authors: G. C. Santini, C. Potrich, L. Lunelli, L. Vanzetti, S. Marasso, M. Cocuzza, C. Pederzolli

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The relevance of circulating miRNAs as non-invasive biomarkers for several pathologies is nowadays undoubtedly clear, as they have been found to have both diagnostic and prognostic value able to add fundamental information to patients’ clinical picture. The availability of these data, however, relies on a time-consuming process spanning from the sample collection and processing to the data analysis. In light of this, strategies which are able to ease this procedure are in high demand and considerable effort have been made in developing Lab-on-a-chip (LOC) devices able to speed up and standardise the bench work. In this context, a very promising polydimethylsiloxane (PDMS)-based microdevice which integrates the processing of the biological sample, i.e. purification of extracellular miRNAs, and reverse transcription was previously developed in our lab. In this study, we aimed at the improvement of the miRNA extraction performances of this micro device by increasing the ability of its surface to absorb extracellular miRNAs from biological samples. For this purpose, we focused on the modulation of two properties of the material: roughness and charge. PDMS surface roughness was modulated by casting with several templates (terminated with silicon oxide coated by a thin anti-adhesion aluminum layer), followed by a panel of curing conditions. Atomic force microscopy (AFM) was employed to estimate changes at the nanometric scale. To introduce modifications in surface charge we functionalized PDMS with different mixes of positively charged 3-aminopropyltrimethoxysilanes (APTMS) and neutral poly(ethylene glycol) silane (PEG). The surface chemical composition was characterized by X-ray photoelectron spectroscopy (XPS) and the number of exposed primary amines was quantified with the reagent sulfosuccinimidyl-4-o-(4,4-dimethoxytrityl) butyrate (s-SDTB). As our final end point, the adsorption rate of all these different conditions was assessed by fluorescence microscopy by incubating a synthetic fluorescently-labeled miRNA. Our preliminary analysis identified casting on thermally grown silicon oxide, followed by a curing step at 85°C for 1 hour, as the most efficient technique to obtain a PDMS surface roughness in the nanometric scaleable to trap miRNA. In addition, functionalisation with 0.1% APTMS and 0.9% PEG was found to be a necessary step to significantly increase the amount of microRNA adsorbed on the surface, therefore, available for further steps as on-chip reverse transcription. These findings show a substantial improvement in the extraction efficiency of our PDMS microdevice, ultimately leading to an important step forward in the development of an innovative, easy-to-use and integrated system for the direct purification of less abundant circulating microRNAs.

Keywords: circulating miRNAs, diagnostics, Lab-on-a-chip, polydimethylsiloxane (PDMS)

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Authors: Maha Atout, Pippa Hemingway, Jane Seymour

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A preliminary systematic review shows that health professionals experience a tension when communicating with the parents and family members of children with life-threatening and life-limiting conditions. On the one hand, they want to promote open and honest communication, while on the other, they are apprehensive about fostering an unrealistic sense of hope. Defining the boundaries between information that might offer reasonable hope versus that which results in false reassurance is challenging. Some healthcare providers worry that instilling a false sense of hope could motivate parents to seek continued aggressive treatment for their child, which in turn might cause the patient further unnecessary suffering. To date, there has been a lack of research in the Middle East regarding how healthcare providers do or should communicate bad news; in particular, the issue of hope in the field of paediatric palliative care has not been researched thoroughly. This study aims to explore, from the perspective of patients’ mothers, physicians, and nurses, the experience of communicating and receiving bad news in the care of children with palliative care needs. Data were collected using a collective qualitative case study approach across three paediatric units in a Jordanian hospital. Two data collection methods were employed: participant observation and semi-structured interviews. The overall number of cases was 15, with a total of 56 interviews with mothers (n=24), physicians (n=12), and nurses (n=20) completed, as well as 197 observational hours logged. The findings demonstrate that mothers wanted their doctors to provide them with hopeful information about the future progression of their child’s illness. Although some mothers asked their doctors to provide them with honest information regarding the condition of their child, they still considered a sense of hope to be essential for coping with caring for their child. According to mothers, hope was critical to treatment as it helped them to stay committed to the treatment and protected them to some extent from the extreme emotional suffering that would occur if they lost hope. The health professionals agreed with the mothers on the importance of hope, so long as it was congruent with the stage and severity of each patient’s disease. The findings of this study conclude that while parents typically insist on knowing all relevant information when their child is diagnosed with a severe illness, they considered hope to be an essential part of life, and they found it very difficult to handle suffering without any glimmer of it. This study finds that using negative terms has extremely adverse effects on the parents’ emotions. Hence, although the mothers asked the doctors to be as honest as they could, they still wanted the physicians to provide them with a positive message by communicating this information in a sensitive manner including hope.

Keywords: health professionals, children, communication, hope, information, mothers, palliative care

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Authors: K. H. Reeta, Bhavana Prasher, Mitali Mukerji, Dhwani Dholakia, Sangeeta Khanna, Archana Vats, Shivam Pandey, Sandeep Seth, Subir Kumar Maulik

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Introduction Research has demonstrated a connection between coronary artery disease (CAD) and genetics. We did a deep literature mining using both bioinformatics and manual efforts to identify the susceptible polymorphisms in coronary artery disease. Further, the study sought to validate these findings in an Asian population. Methodology In first phase, we used an automated pipeline which organizes and presents structured information on SNPs, Population and Diseases. The information was obtained by applying Natural Language Processing (NLP) techniques to approximately 28 million PubMed abstracts. To accomplish this, we utilized Python scripts to extract and curate disease-related data, filter out false positives, and categorize them into 24 hierarchical groups using named Entity Recognition (NER) algorithms. From the extensive research conducted, a total of 466 unique PubMed Identifiers (PMIDs) and 694 Single Nucleotide Polymorphisms (SNPs) related to coronary artery disease (CAD) were identified. To refine the selection process, a thorough manual examination of all the studies was carried out. Specifically, SNPs that demonstrated susceptibility to CAD and exhibited a positive Odds Ratio (OR) were selected, and a final pool of 324 SNPs was compiled. The next phase involved validating the identified SNPs in DNA samples of 96 CAD patients and 37 healthy controls from Indian population using Global Screening Array. ResultsThe results exhibited out of 324, only 108 SNPs were expressed, further 4 SNPs showed significant difference of minor allele frequency in cases and controls. These were rs187238 of IL-18 gene, rs731236 of VDR gene, rs11556218 of IL16 gene and rs5882 of CETP gene. Prior researches have reported association of these SNPs with various pathways like endothelial damage, susceptibility of vitamin D receptor (VDR) polymorphisms, and reduction of HDL-cholesterol levels, ultimately leading to the development of CAD. Among these, only rs731236 had been studied in Indian population and that too in diabetes and vitamin D deficiency. For the first time, these SNPs were reported to be associated with CAD in Indian population. Conclusion: This pool of 324 SNP s is a unique kind of resource that can help to uncover risk associations in CAD. Here, we validated in Indian population. Further, validation in different populations may offer valuable insights and contribute to the development of a screening tool and may help in enabling the implementation of primary prevention strategies targeted at the vulnerable population.

Keywords: coronary artery disease, single nucleotide polymorphism, susceptible SNP, bioinformatics

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Authors: Klaus Peter Scherer, Daniel Knöll, Constantin Rieder

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Problem and Purpose: Intelligent systems are available and helpful to support the human being decision process, especially when complex surgical eye interventions are necessary and must be performed. Normally, such a decision support system consists of a knowledge-based module, which is responsible for the real assistance power, given by an explanation and logical reasoning processes. The interview based acquisition and generation of the complex knowledge itself is very crucial, because there are different correlations between the complex parameters. So, in this project (semi)automated self-learning methods are researched and developed for an enhancement of the quality of such a decision support system. Methods: For ophthalmic data sets of real patients in a hospital, advanced data mining procedures seem to be very helpful. Especially subgroup analysis methods are developed, extended and used to analyze and find out the correlations and conditional dependencies between the structured patient data. After finding causal dependencies, a ranking must be performed for the generation of rule-based representations. For this, anonymous patient data are transformed into a special machine language format. The imported data are used as input for algorithms of conditioned probability methods to calculate the parameter distributions concerning a special given goal parameter. Results: In the field of knowledge discovery advanced methods and applications could be performed to produce operation and patient related correlations. So, new knowledge was generated by finding causal relations between the operational equipment, the medical instances and patient specific history by a dependency ranking process. After transformation in association rules logically based representations were available for the clinical experts to evaluate the new knowledge. The structured data sets take account of about 80 parameters as special characteristic features per patient. For different extended patient groups (100, 300, 500), as well one target value as well multi-target values were set for the subgroup analysis. So the newly generated hypotheses could be interpreted regarding the dependency or independency of patient number. Conclusions: The aim and the advantage of such a semi-automatically self-learning process are the extensions of the knowledge base by finding new parameter correlations. The discovered knowledge is transformed into association rules and serves as rule-based representation of the knowledge in the knowledge base. Even more, than one goal parameter of interest can be considered by the semi-automated learning process. With ranking procedures, the most strong premises and also conjunctive associated conditions can be found to conclude the interested goal parameter. So the knowledge, hidden in structured tables or lists can be extracted as rule-based representation. This is a real assistance power for the communication with the clinical experts.

Keywords: an expert system, knowledge-based support, ophthalmic decision support, self-learning methods

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