Search results for: Carl Lachat
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 55

Search results for: Carl Lachat

25 Obesity, Leptin Levels and Leptin Receptor Gene Polymorphisms in Afro-Caribbean Subjects

Authors: Lydia Foucan, Christine Rambhojan, Rachel Billy, Christophe Armand, Carl-Thony Michel, Jean-Marc Lacorte, Laurent Larifla

Abstract:

Leptin, an adipocyte-derived hormone, modulates insulin secretion and action via the leptin receptor (LEPR) that is expressed in pancreatic beta cells, adipose tissue, and muscle. Several polymorphisms have been described in the human LEPR gene including p.K109R (rs1137100), p.Q223R (rs1137101) and p.K656N (rs1805094) polymorphisms. The role of these polymorphisms is not yet studied in Guadeloupian population. Our aim was to explore the association of LEPR polymorphisms (K109R, Q223R and K656N) with leptin levels and obesity in non-diabetic Afro-Caribbean subjects. Genotypic analysis of the three polymorphisms was performed in 425 subjects using TaqMan and KASPar Assays. Serum leptin was measured with ELISA kits Biovendor® (RD191001100). Logistic regressions were used for assessment of statistical associations. Mean age was 47.6 ± 12.7 years. Among the participants, 238 (56 %) were women, 124 (30%) were obese and 155 (36.5%) had abdominal obesity. Carriers of LEPR K656N rs1805094 rare allele had significant higher frequencies of obesity (P = 0.007), abdominal obesity (P = 0.004) and metabolic syndrome (P = 0.021) but mean leptin level was not significantly different between both groups (P = 0.075). Odds ratios, adjusted for age and sex associated with presence of rs1805094 rare allele were 1.8 (1.1-2.9), P = 0.012 for obesity, 2.0 (1.2-3.3), P = 0.008 for abdominal obesity and 1.8 (1.1-3.0), P = 0.031 for MetS. No significant association was found with K109R, Q223R. These findings suggest that the K656N polymorphism (but not the K109R or Q223R polymorphism) of LEPR is associated with obesity, abdominal obesity and metabolic syndrome in this Afro-Caribbean non-diabetic population.

Keywords: Afro-Caribbean, leptin levels, leptin receptor gene polymorphisms, obesity

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24 Confess Your Sins to One Another: An Exploration of the Biblical Validity and the Psychological Efficacy of the Sacrament of Reconciliation in the Catholic Church

Authors: M. B. Peter

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The Sacrament of Penance and Reconciliation has long been upheld, by the Catholic Church, as one of the Sacraments of healing, mainly due to the sense of peace, tranquility and psychological quiescence it accords the penitent upon receiving Sacramental absolution of sin through the action of the priest. This paper explores the Sacramental character of this practice and the psychological benefits of the celebration of the Sacrament. This is achieved in two parts: firstly, by the intellectual engagement of Sacred Scripture and the consolidated Sacred Tradition that the Catholic magisterium protects and, secondly, via a broad survey of the works of Carl Gustav Jung and Orval Hobart Mowrer regarding confession and forgiveness. The former will serve to demonstrate the Catholic belief of the divine institution of the Sacrament whilst the latter will demonstrate how this belief, coupled with the existing benefit of confessing guilt, collectively bolsters the Sacrament’s overall psychological efficacy. Fundamentally, the analysis of Jung and Mowrer’s works demonstrate that man, as a naturally religious being, has an inherent need for the confession of his wrong that he might be alleviated of psychological guilt in obtaining forgiveness of a (divinely ordained) minister who is sanctioned to absolve, i.e. the priest. The paper also presents the curative effect of the celebration of this Sacrament, illustrating how, without the act of confession, man remains in moral isolation from God and man; and, that with it, man is relieved of the mysterious feeling of guilt which lies at the root of his disquiet of mind and disturbance of will. Thus, the paper penultimately establishes how the Sacrament of Reconciliation is positioned in that place where psychology and theology meet: man’s sense of guilt. It is Jung’s views on confession and forgiveness that ultimately bridge the chasm between psychology and Christianity.

Keywords: Catholic, confession, Jung, Mowrer, penance, psychology, Sacrament of Reconciliation

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23 Archetypes in the Rorschach Inkblots: Imparting Universal Meaning in the Face of Ambiguity

Authors: Donna L. Roberts

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The theory of archetypes contends that themes based on universal foundational images reside in and are transmitted generationally through the collective unconscious, which is referenced throughout an individual’s experience in order to make sense of that experience. There is then, a profoundly visceral and instinctive agreement on the gestalt of these universal themes and how they apply to the human condition throughout space and time. The inherent nature of projective tests, such as the Rorschach Inkblot, necessitates that the stimulus is ambiguous and thus elicits responses that reflect the unconscious inner psyche of the respondent. As the development of the Rorschach inkblots was relatively random and serendipitous - i.e., the inkblots were not engineered to elicit a specifically defined response - it would stand to reason that without a collective unconscious, every individual would interpret the inkblots in an individualized and unique way. Yet this is not the case. Instead, common themes appear in the images of the inkblots and their interpretation that reflect this deeper iconic understanding. This study analyzed the ten Rorschach inkblots in terms of Jungian archetypes, both with respect to the form of images on each plate and the commonly observed themes in responses. Examples of the archetypes were compared to each of the inkblots, with subsequent descriptions matched to the standard responses. The findings yielded clear and distinct instances of the universal symbolism intrinsic in the inkblot images as well as ubiquitous throughout the responses. This project illustrates the influence of the theories of psychologist Carl Gustav Jung on the interpretation of the ambiguous stimuli. It further serves to demonstrate the merit of Jungian psychology as a valuable tool with which to understand the nature of projective tests in general, Rorschach’s work specifically, and ultimately the broader implications for our collective unconscious and common humanity.

Keywords: archetypes, inkblots, projective tests, Rorschach

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22 Physical Activity, Exercise and Physical Fitness in Different Generation

Authors: Carl J. Caspersen, Kenneth E. Powell, Gregory M. Christenson, Kirupa V. Patel

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‘Physical activity’, ‘exercise’, and ‘physical fitness’ are terms that describe different concepts. However, they are often confused with one another, and the terms are sometimes used interchangeably. This paper proposes definitions to distinguish them. Physical activity is defined as any bodily movement produced by skeletal muscles that result in energy expenditure. The energy expenditure can be measured in kilocalories. Physical activity in daily life can be categorized into occupational, sports, Conditioning, household, or other activities. Exercise is a subset of physical activity that is planned, structured, and repetitive and has as a final or an intermediate objective the improvement or maintenance of physical fitness. Physical fitness is a set of attributes that are either health- or skill-related. The degree to which people have these attributes can be measured with specific tests. These definitions are offered as an interpretational framework for comparing studies that relate physical activity, exercise, and physical fitness to health. Physical activity is defined as any bodily movement produced by skeletal muscles that require energy expenditure. Physical inactivity has been identified as the fourth leading risk factor for global mortality causing an estimated 3.2 million deaths globally. Regular moderate intensity physical activity – such as walking, cycling, or participating in sports – has significant benefits for health. For instance, it can reduce the risk of cardiovascular diseases, diabetes, colon and breast cancer, and depression. Moreover, adequate levels of physical activity will decrease the risk of a hip or vertebral fracture and help control weight. Any bodily movement produced by the contraction of skeletal muscle that increases energy expenditure above a basal level. In these guidelines, physical activity generally refers to the subset of physical activity that enhances health.

Keywords: physical activity, exercise, physical fitness, sports

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21 Cosmic Muon Tomography at the Wylfa Reactor Site Using an Anti-Neutrino Detector

Authors: Ronald Collins, Jonathon Coleman, Joel Dasari, George Holt, Carl Metelko, Matthew Murdoch, Alexander Morgan, Yan-Jie Schnellbach, Robert Mills, Gareth Edwards, Alexander Roberts

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At the Wylfa Magnox Power Plant between 2014–2016, the VIDARR prototype anti-neutrino detector was deployed. It is comprised of extruded plastic scintillating bars measuring 4 cm × 1 cm × 152 cm and utilised wavelength shifting fibres (WLS) and multi-pixel photon counters (MPPCs) to detect and quantify radiation. During deployment, it took cosmic muon data in accidental coincidence with the anti-neutrino measurements with the power plant site buildings obscuring the muon sky. Cosmic muons have a significantly higher probability of being attenuated and/or absorbed by denser objects, and so one-sided cosmic muon tomography was utilised to image the reactor site buildings. In order to achieve clear building outlines, a control data set was taken at the University of Liverpool from 2016 – 2018, which had minimal occlusion of the cosmic muon flux by dense objects. By taking the ratio of these two data sets and using GEANT4 simulations, it is possible to perform a one-sided cosmic muon tomography analysis. This analysis can be used to discern specific buildings, building heights, and features at the Wylfa reactor site, including the reactor core/reactor core shielding using ∼ 3 hours worth of cosmic-ray detector live time. This result demonstrates the feasibility of using cosmic muon analysis to determine a segmented detector’s location with respect to surrounding buildings, assisted by aerial photography or satellite imagery.

Keywords: anti-neutrino, GEANT4, muon, tomography, occlusion

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20 Evaluation of Elements Impurities in Drugs According to Pharmacopoeia by use FESEM-EDS Technique

Authors: Rafid Doulab

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Elemental Impurities in the Pharmaceuticals industryis are indispensable to ensure pharmaceuticalssafety for 24 elements. Although atomic absorption and inductively coupled plasma are used in the U.S Pharmacopeia and the European Pharmacopoeia, FESEM with energy dispersive spectrometers can be applied as an alternative analysis method for quantitative and qualitative results for a variety of elements without chemical pretreatment, unlike other techniques. This technique characterizes by shortest time, with more less contamination, no reagent consumption, and generation of minimal residue or waste, as well as sample preparations time limiting, with minimal analysis error. Simple dilution for powder or direct analysis for liquid, we analyzed the usefulness of EDS method in testing with field emission scanning electron microscopy (FESEM, SUPRA 55 Carl Zeiss Germany) with an X-ray energy dispersion (XFlash6l10 Bruker Germany). The samples analyzed directly without coating by applied 5µ of known concentrated diluted sample on carbon stub with accelerated voltage according to sample thickness, the result for this spot was in atomic percentage, and by Avogadro converted factor, the final result will be in microgram. Conclusion and recommendation: The conclusion of this study is application of FESEM-EDS in US pharmacopeia and ICH /Q3D guideline to reach a high-precision and accurate method in element impurities analysis of drugs or bulk materials to determine the permitted daily exposure PDE in liquid or solid specimens, and to obtain better results than other techniques, by the way it does not require complex methods or chemicals for digestion, which interfere with the final results with the possibility of to keep the sample at any time for re analysis. The recommendation is to use this technique in pharmacopeia as standard methods like inductively coupled plasma both ICP-AES, ICP-OES, and ICP-MS.

Keywords: pharmacopoeia, FESEM-EDS, element impurities, atomic concentration

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19 Behavior of Common Philippine-Made Concrete Hollow Block Structures Subjected to Seismic Load Using Rigid Body Spring-Discrete Element Method

Authors: Arwin Malabanan, Carl Chester Ragudo, Jerome Tadiosa, John Dee Mangoba, Eric Augustus Tingatinga, Romeo Eliezer Longalong

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Concrete hollow blocks (CHB) are the most commonly used masonry block for walls in residential houses, school buildings and public buildings in the Philippines. During the recent 2013 Bohol earthquake (Mw 7.2), it has been proven that CHB walls are very vulnerable to severe external action like strong ground motion. In this paper, a numerical model of CHB structures is proposed, and seismic behavior of CHB houses is presented. In modeling, the Rigid Body Spring-Discrete Element method (RBS-DEM)) is used wherein masonry blocks are discretized into rigid elements and connected by nonlinear springs at preselected contact points. The shear and normal stiffness of springs are derived from the material properties of CHB unit incorporating the grout and mortar fillings through the volumetric transformation of the dimension using material ratio. Numerical models of reinforced and unreinforced walls are first subjected to linearly-increasing in plane loading to observe the different failure mechanisms. These wall models are then assembled to form typical model masonry houses and then subjected to the El Centro and Pacoima earthquake records. Numerical simulations show that the elastic, failure and collapse behavior of the model houses agree well with shaking table tests results. The effectiveness of the method in replicating failure patterns will serve as a basis for the improvement of the design and provides a good basis of strengthening the structure.

Keywords: concrete hollow blocks, discrete element method, earthquake, rigid body spring model

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18 Evidence of Natural Selection Footprints among Some African Chicken Breeds and Village Ecotypes

Authors: Ahmed Elbeltagy, Francesca Bertolini, Damarius Fleming, Angelica Van Goor, Chris Ashwell, Carl Schmidt, Donald Kugonza, Susan Lamont, Max Rothschild

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The major factor in shaping genomic variation of the African indigenous rural chicken is likely natural selection drives the development genetic footprints in the chicken genomes. To investigate such a hypothesis of a selection footprint, a total of 292 birds were randomly sampled from three indigenous ecotypes from East Africa (Uganda, Rwanda) and North Africa (Egypt) and two registered Egyptian breeds (Fayoumi and Dandarawi), and from the synthetic Kuroiler breed. Samples were genotyped using the Affymetrix 600K Axiom® Array. A total of 526,652 SNPs were utilized in the downstream analysis after quality control measures. The intra-population runs of homozygosity (ROH) that were consensuses in > 50% of individuals of an ecotype or > 75% of a breed were studied. To identify inter-population differentiation due to genetic structure, FST was calculated for North- vs. East- African populations in addition to population-pairwise combinations for overlapping windows (500Kb with an overlap of 250Kb). A total of 28,563 ROH were determined and were classified into three length categories. ROH and Fst detected sweeps were identified on several autosomes. Several genes in these regions are likely to be related to adaptation to local environmental stresses that include high altitude, diseases resistance, poor nutrition, oxidative and heat stresses and were linked to gene ontology terms (GO) related to immune response, oxygen consumption and heme binding, carbohydrate metabolism, oxidation-reduction, and behavior. Results indicated a possible effect of natural selection forces on shaping genomic structure for adaptation to local environmental stresses.

Keywords: African Chicken, runs of homozygosity, FST, selection footprints

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17 Open Innovation in SMEs: A Multiple Case Study of Collaboration between Start-ups and Craft Enterprises

Authors: Carl-Philipp Valentin Beichert, Marcel Seger

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Digital transformation and climate change require small and medium-sized enterprises (SME) to rethink their way of doing business. Inter-firm collaboration is recognized as helpful means of promoting innovation and competitiveness. In this context, collaborations with start-ups offer valuable opportunities through their innovative products, services, and business models. SMEs, and in particular German craft enterprises, play an important role in the country’s society and economy. Companies in this heterogeneous economic sector have unique characteristics and are limited in their ability to innovate due to their small size and lack of resources. Collaborating with start-ups could help to overcome these shortcomings. To investigate how collaborations emerge and what factors are decisive to successfully drive collaboration, we apply an explorative, qualitative research design. A sample of ten case studies was selected, with the collaboration between a start-up and a craft enterprise forming the unit of analysis. Semi-structured interviews with 20 company representatives allow for a two-sided perspective on the respective collaboration. The interview data is enriched by publicly available data and three expert interviews. As a result, objectives, initiation practices, applied collaboration types, barriers, as well as key success factors could be identified. The results indicate a three-phase collaboration process comprising an initiation, concept, and partner phase (ICP). The ICP framework proposed accordingly highlights the success factors (personal fit, communication, expertise, structure, network) for craft enterprises and start-ups for each collaboration phase. The role of a mediator in the start-up company, with strong expertise in the respective craft sector, is considered an important lever for overcoming barriers such as cultural and communication differences. The ICP framework thus provides promising directions for further research and can help practitioners establish successful collaborations.

Keywords: open innovation, SME, craft businesses, startup collaboration, qualitative research

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16 E-Government Development in Nigeria, 'Bank Verification No': An Anti-Corruption Tool

Authors: Ernest C. Nwadinobi, Amanda Peart, Carl Adams

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The leading countries like the USA, UK and some of the European countries have moved their focus away from just developing the e-government platform towards just the electronic services which aim at providing access to information to its citizens or customers, but they have gone to make significant backroom changes that can accommodate this electronic service being provided to its customers or citizens. E-government has moved from just providing electronic information to citizens and customers alike to serving their needs. In developing countries like Nigeria, the enablement of e-government is being used as an anti-corruption tool. The introduction of the Bank verification number (BVN) scheme by the Central Bank of Nigeria, has helped the government in not just saving money but also protecting customer’s transaction and enhancing confidence in the banking sector. This has helped curtail the high rate of cyber and financial crime that has been part of the system. The use of BVN as an anti-corruption tool in Nigeria came at a time there was need for openness, accountability, and discipline, after years of robbing the treasury and recklessness in handling finances. As there has not been a defined method for measuring the strength or success of e-government development, in this case BVN, in Nigeria, progress will remain at the same level. The implementation strategy of the BVN in Nigeria has mostly been a quick fix, quick win solution. In fact, there is little or no indication to show evidence of a framework for e-government. Like other leading countries, there is the need for proper implementation of strategy and framework especially towards a customer orientated process, which will accommodate every administrative body of the government institution including private business rather than focusing on a non-flexible organisational structure. The development of e-government must have a strategy and framework for it to work, and this strategy must enclose every public administration and will not be limited to any individual bodies or organization. A defined framework or monitoring method must be put in place to help evaluate and benchmark government development in e-government. This framework must follow the same concept or principles. In censorious analyses of the existing methods, this paper will denote areas that must be included in the existing approach to be able to channel e-government development towards its defined strategic objectives.

Keywords: Bank Verification No (BVN), quick-fix, anti-corruption, quick-win

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15 History of Pediatric Renal Pathology

Authors: Mostafa Elbaba

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Because childhood renal diseases are grossly different compared to adult diseases, pediatric nephrology was founded as a specialty in 1965. Renal pathology specialty was introduced at the London Ciba Symposium in 1961. The history of renal pathology can be divided into two eras: one starting in the 1650s with the invention of the microscope, the second in the 1950s with the implementation of renal biopsy, and the presence of electron microscopy and immunofluorescence study. Prior to the 1950s, the study of diseased human kidneys was restricted to postmortem examination by gross pathology. In 1827, Richard Bright first described his triad of kidney disease, which was confirmed by morbid kidney changes at autopsy. In 1905 Friedrich Mueller coined the term “nephrosis” describing the inflammatory form of “degenerative” diseases, and later F. Munk added the term “lipoid nephrosis”. The most profound influence on renal diseases’ classification came from the publication of Volhard and Fahr in 1914. In 1899, Carl Max Wilhelm Wilms described Wilms' tumor of the kidneys in children. Chronic pyelonephritis was a popular renal diagnosis and the most common cause of uremia until the 1960s. Although kidney biopsy had been used early in the 1930s for renal tumors, the earliest reports of its use in the diagnosis of medical kidney disease were by Iversen and Brun in 1951, followed by Alwall in 1952, then by Pardo in 1953. The earliest intentional renal biopsies were done in 1944 by Nils Alwall, while the procedure was abandoned after the death of one of his 13 patients who biopsied. In 1950, Antonino Perez-Ara attempted renal biopsies, but his results were missed because of an unpopular journal publication. In the year 1951, Claus Brun and Poul Iverson developed the biopsy procedure using an aspiration technique. Popularizing renal biopsy practice is accredited to Robert Kark, who published his distinct work in 1954. He perfected the technique of renal biopsy in the prone position using the Vim-Silverman needle and used intravenous pyelography to improve the localization of the kidney.

Keywords: history, medicine, nephrology, pediatrics, pathology

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14 Relationship Building Between Peer Support Worker and Person in Recovery in the Community-based One-to-One Peer Support Service of Mental Health Setting

Authors: Yuen Man Yan

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Peer support has been a rising prevalent mental health service in the globe. The community-based mental health services employ persons with lived experience of mental illness to be peer support workers (PSWs) to provide peer support service to those who are in the progress of recovery (PIRs). It represents the transformation of mental health service system to a recovery-oriented and person-centered care. Literatures proved the feasibility and effectiveness of the peer support service. Researchers have attempted to explore the unique good qualities of peer support service that benefit the PIRs. Empirical researches found that the strength of the relationship between those who sought for change and the change agents positively related to the outcomes in one-to-one therapies across theoretical orientations. However, there is lack of literature on investigating the relationship building between the PSWs and PIRs in the one-to-one community-based peer support service. This study aims to identify and characterise the relationship in the community-based one-to-one peer support service from the perspectives of PSWs and PIRs; and to conceptualize the components of relationship building between PSWs and PIRs in the community-based one-to-one peer support service. The study adopted the constructivist grounded theory approach. 10 pairs of the PSWs and PIRs participated in the study. Data were collected through multiple qualitative methods, including observation of the interaction and exchange of the PSWs and PIRs in the 1ₛₜ, 3ᵣ𝒹 and 9th sessions of the community-based one-to-one peer support service; and semi-structural interview with the PSWs and PIRs separately after the 3ᵣ𝒹and 9ₜₕ session of the peer support service. This presentation is going to report the preliminary findings of the study. PSWs and PIRs identified their relationship as “life alliance”. Empathy was found to be one of key components of the relationship between the PSWs and the PIRs. Unlike the empathy, as explained by Carl Roger, in which the service provider was able to put themselves into the shoes of the service recipients as if he was the service recipients, the intensity of the empathy was much greater in the relationship between PSWs and PIRs because PSWs had the lived experience of mental illness and recovery. The dimensions of the empathy in the relationship between PSWs and PIRs was found to be multiple, not only related to the mental illness but also related to various aspects in life, like family relationship, employment, interest of life, self-esteem and etc.

Keywords: person with lived experience, peer support worker, peer support service, relationship building, therapeutic alliance, community-based mental health setting

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13 Assessment of Health Literacy and Awareness of Female Residents of Barangay Dagatan, Sabang, and Marauoy Lipa, Batangas on Polycystic Ovarian Syndrome: A Cross-Sectional Study

Authors: Jean Gray C. Achapero, Mary Margareth P. Ancheta, Patricia Anjelika A. Angeles, Shannon Denzel S. Ao Tai, Carl Brandon C. Barlis, Chrislen Mae B. Benavidez

Abstract:

Health literacy and awareness of Polycystic ovarian syndrome (PCOS) is a global issue that is under-addressed in the Philippines. Conducting a thorough review of the country's ability to recognize and comprehend the severity of the syndrome should be undertaken, as early treatment is essential to avoid further disorder complications. This research aims to assess the health literacy and awareness of the female residents of Barangay Dagatan, Sabang, and Marauoy Lipa, Batangas on PCOS. It followed a cross-sectional study, and data gathering was done through a pre-assessment using the Single Item Literacy Screener (SILS) and an online population-based survey questionnaire about PCOS awareness. The participants, as based on the objectives and purposive sampling method, were females aged 18-45 years old. Data were analyzed statistically using STATA 13.1 software. The study showed that 339 (76%) out of 444 respondents passed the SILS meaning the residents have proficient health literacy. Among the 339 respondents, 87% (287) had previous knowledge about PCOS. The respondents showed minimal awareness of PCOS symptoms which could be attributed to its broad spectrum of information. Respondents were shown to be most knowledgeable about PCOS physiology, treatment, beliefs, and its remedies. The respondents’ age had no significant association with their health literacy (p=0.31) and PCOS awareness (p=0.60). A significant association was noted, however, in their educational attainment linked with their health literacy (p=<0.0001) and PCOS awareness (p=0.001). It is suggested that reproductive health education even in the lower year levels must be optimized and Local Government Unit (LGU)/Non-Government Organization (NGO)-held seminars should be conducted for knowledge reinforcement. Reliable health information should be more accessible to the public and clinicians must emphasize the importance of the majority of early screening as part of routine physical examination for women of reproductive age to increase health literacy and awareness about PCOS and actively engage in the management of the disease.

Keywords: age, awareness, educational attainment, health literacy, polycystic ovarian syndrome

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12 The Analgesic Impact of Adding Intrathecal Ketamine to Spinal Anaesthesia for Hip or Knee Arthroplasty: A Clinical Audit

Authors: Carl Ashworth, Matthys Campher

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Spinal anaesthesia has been identified as the “gold standard” for primary elective total hip and knee arthroplasty, which is most commonly performed using longer-acting local anaesthetics, such as hyperbaric bupivacaine, to prolong the duration of anaesthesia and analgesia suitable for these procedures. Ketamine is known to have local anaesthetic effects with potent analgesic properties and has been evaluated as a sole anaesthetic agent via intrathecal administration; however, the use of intrathecal ketamine as an adjunct to intrathecal hyperbaric bupivacaine, morphine, and fentanyl has not been extensively studied. The objective of this study was to identify the potential analgesic effects of the addition of intrathecal ketamine to spinal anaesthesia and to compare the efficacy and safety of adding intrathecal ketamine to spinal anaesthesia for hip- or knee arthroplasty with spinal anaesthesia for hip- or knee arthroplasty without intrathecal ketamine. The medical records of patients who underwent elective hip- or knee arthroplasty under spinal anaesthesia performed by an individual anaesthetist with either intrathecal hyperbaric bupivacaine, morphine and fentanyl or intrathecal hyperbaric bupivacaine, morphine, fentanyl and ketamine between June 4, 2020, and June 4, 2022, were retrospectively reviewed. These encounters were reviewed and analyzed from a perioperative pain perspective, with the primary outcome measure as the oral morphine equivalent (OME) usage in the 48 hours post-spinal anaesthesia, and secondary outcome measures including time to breakthrough analgesia, self-reported pain scores at rest and during movement at 24 and 48 hours after surgery, adverse effects of analgesia, complications, and length of stay. There were 26 patients identified who underwent TKR between June 4, 2020, and June 4, 2022, and 25 patients who underwent THR with the same conditions. It was identified that patients who underwent traditional spinal anaesthesia with the addition of ketamine for elective hip- or knee arthroplasty had a lower mean total OME in the 48 hours immediately post-spinal anaesthesia yet had a shorter time to breakthrough analgesia administration. The proposed mechanism of action for intrathecal ketamine as an additive to traditional spinal anaesthesia for elective hip- or knee arthroplasty is that it may prolong and attenuate the analgesic effect of traditional spinal anaesthesia. There were no significant differences identified in comparing the efficacy and safety of adding intrathecal ketamine to spinal anaesthesia for hip- or knee arthroplasty with spinal anaesthesia for hip- or knee arthroplasty without intrathecal ketamine.

Keywords: anaesthesia, spinal, intra-thecal, ketamine, spinal-morphine, bupivacaine

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11 Humanistic Psychology Workshop to Increase Psychological Well-Being

Authors: Nidia Thalia Alva Rangel, Ferran Padros Blazquez, Ma. Ines Gomez Del Campo Del Paso

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Happiness has been since antiquity a concept of interest around the world. Positive psychology is the science that begins to study happiness in a more precise and controlled way, obtaining wide amount of research which can be applied. One of the central constructs of Positive Psychology is Carol Ryff’s psychological well-being model as eudaimonic happiness, which comprehends six dimensions: autonomy, environmental mastery, personal growth, positive relations with others, purpose in life, and self-acceptance. Humanistic psychology is a clear precedent of Positive Psychology, which has studied human development topics and it features a great variety of intervention techniques nevertheless has little evidence with controlled research. Therefore, the present research had the aim to evaluate the efficacy of a humanistic intervention program to increase psychological well-being in healthy adults through a mixed methods study. Before and after the intervention, it was applied Carol Ryff’s psychological well-being scale (PWBS) and the Symptom Check List 90 as pretest and posttest. In addition, a questionnaire of five open questions was applied after each session. The intervention program was designed in experiential workshop format, based on the foundational attitudes defined by Carl Rogers: congruence, unconditional positive regard and empathy, integrating humanistic intervention strategies from gestalt, psychodrama, logotherapy and psychological body therapy, with the aim to strengthen skills in the six dimensions of psychological well-being model. The workshop was applied to six volunteer adults in 12 sessions of 2 hours each. Finally, quantitative data were analyzed with Wilcoxon statistic test through the SPSS program, obtaining as results differences statistically significant in pathology symptoms between prettest and postest, also levels of dimensions of psychological well-being were increased, on the other hand for qualitative strand, by open questionnaires it showed how the participants were experiencing the techniques and changing through the sessions. Thus, the humanistic psychology program was effective to increase psychological well-being. Working to promote well-being prompts to be an effective way to reduce pathological symptoms as a secondary gain. Experiential workshops are a useful tool for small groups. There exists the need for research to count with more evidence of humanistic psychology interventions in different contexts and impulse the application of Positive Psychology knowledge.

Keywords: happiness, humanistic psychology, positive psychology, psychological well-being, workshop

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10 Multiaxial Fatigue in Thermal Elastohydrodynamic Lubricated Contacts with Asperities and Slip

Authors: Carl-Magnus Everitt, Bo Alfredsson

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Contact mechanics and tribology have been combined with fundamental fatigue and fracture mechanics to form the asperity mechanism which supplies an explanation for the surface-initiated rolling contact fatigue damage, called pitting or spalling. The cracks causing the pits initiates at one surface point and thereafter they slowly grow into the material before chipping of a material piece to form the pit. In the current study, the lubrication aspects on fatigue initiation are simulated by passing a single asperity through a thermal elastohydrodynamic lubricated, TEHL, contact. The physics of the lubricant was described with Reynolds equation and the lubricants pressure-viscosity relation was modeled by Roelands equation, formulated to include temperature dependence. A pressure dependent shear limit was incorporated. To capture the full phenomena of the sliding contact the temperature field was resolved through the incorporation of the energy flow. The heat was mainly generated due to shearing of the lubricant and from dry friction where metal contact occurred. The heat was then transported, and conducted, away by the solids and the lubricant. The fatigue damage caused by the asperities was evaluated through Findley’s fatigue criterion. The results show that asperities, in the size of surface roughness found in applications, may cause surface initiated fatigue damage and crack initiation. The simulations also show that the asperities broke through the lubricant in the inlet, causing metal to metal contact with high friction. When the asperities thereafter moved through the contact, the sliding provided the asperities with lubricant releasing the metal contact. The release of metal contact was possible due to the high viscosity the lubricant obtained from the high pressure. The metal contact in the inlet caused higher friction which increased the risk of fatigue damage. Since the metal contact occurred in the inlet it increased the fatigue risk more for asperities subjected to negative slip than positive slip. Therefore the fatigue evaluations showed that the asperities subjected to negative slip yielded higher fatigue stresses than the asperities subjected to positive slip of equal magnitude. This is one explanation for why pitting is more common in the dedendum than the addendum on pinion gear teeth. The simulations produced further validation for the asperity mechanism by showing that asperities cause surface initiated fatigue and crack initiation.

Keywords: fatigue, rolling, sliding, thermal elastohydrodynamic

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9 Functionalization of Carbon-Coated Iron Nanoparticles with Fluorescent Protein

Authors: A. G. Pershina, P. S. Postnikov, M. E. Trusova, D. O. Burlakova, A. E. Sazonov

Abstract:

Invention of magnetic-fluorescent nanocomposites is a rapidly developing area of research. The magnetic-fluorescent nanocomposite attractiveness is connected with the ability of simultaneous management and control of such nanocomposites by two independent methods based on different physical principles. These nanocomposites are applied for the solution of various essential scientific and experimental biomedical problems. The aim of this research is development of principle approach to nanobiohybrid structures with magnetic and fluorescent properties design. The surface of carbon-coated iron nanoparticles (Fe@C) were covalently modified by 4-carboxy benzenediazonium tosylate. Recombinant fluorescent protein TagGFP2 (Eurogen) was obtained in E. coli (Rosetta DE3) by standard laboratory techniques. Immobilization of TagGFP2 on the nanoparticles surface was provided by the carbodiimide activation. The amount of COOH-groups on the nanoparticle surface was estimated by elemental analysis (Elementar Vario Macro) and TGA-analysis (SDT Q600, TA Instruments. Obtained nanocomposites were analyzed by FTIR spectroscopy (Nicolet Thermo 5700) and fluorescence microscopy (AxioImager M1, Carl Zeiss). Amount of the protein immobilized on the modified nanoparticle surface was determined by fluorimetry (Cary Eclipse) and spectrophotometry (Unico 2800) with the help of preliminary obtained calibration plots. In the FTIR spectra of modified nanoparticles the adsorption band of –COOH group around 1700 cm-1 and bands in the region of 450-850 cm-1 caused by bending vibrations of benzene ring were observed. The calculated quantity of active groups on the surface was equal to 0,1 mmol/g of material. The carbodiimide activation of COOH-groups on nanoparticles surface results to covalent immobilization of TagGFP2 fluorescent protein (0.2 nmol/mg). The success of immobilization was proved by FTIR spectroscopy. Protein characteristic adsorption bands in the region of 1500-1600 cm-1 (amide I) were presented in the FTIR spectrum of nanocomposite. The fluorescence microscopy analysis shows that Fe@C-TagGFP2 nanocomposite possesses fluorescence properties. This fact confirms that TagGFP2 protein retains its conformation due to immobilization on nanoparticles surface. Magnetic-fluorescent nanocomposite was obtained as a result of unique design solution implementation – the fluorescent protein molecules were fixed to the surface of superparamagnetic carbon-coated iron nanoparticles using original diazonium salts.

Keywords: carbon-coated iron nanoparticles, diazonium salts, fluorescent protein, immobilization

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8 The Production of Reinforced Insulation Bricks out of the Concentration of Ganoderma lucidum Fungal Inoculums and Cement Paste

Authors: Jovie Esquivias Nicolas, Ron Aldrin Lontoc Austria, Crisabelle Belleza Bautista, Mariane Chiho Espinosa Bundalian, Owwen Kervy Del Rosario Castillo, Mary Angelyn Mercado Dela Cruz, Heinrich Theraja Recana De Luna, Chriscell Gipanao Eustaquio, Desiree Laine Lauz Gilbas, Jordan Ignacio Legaspi, Larah Denise David Madrid, Charles Linelle Malapote Mendoza, Hazel Maxine Manalad Reyes, Carl Justine Nabora Saberdo, Claire Mae Rendon Santos

Abstract:

In response to the global race in discovering the next advanced sustainable material that will reduce our ecological footprint, the researchers aimed to create a masonry unit which is competent in physical edifices and other constructional facets. From different proven researches, mycelium has been concluded that when dried can be used as a robust and waterproof building material that can be grown into explicit forms, thus reducing the processing requirements. Hypothesizing inclusive measures to attest fungi’s impressive structural qualities and absorbency, the researchers projected to perform comparative analyses in creating mycelium bricks from mushroom spores of G. lucidum. Three treatments were intended to classify the most ideal concentration of clay and substrate fixings. The substrate bags fixed with 30% clay and 70% mixings indicated highest numerical frequencies in terms of full occupation of fungal mycelia. Subsequently, sorted parts of white portions from the treatment were settled in a thermoplastic mold and burnt. Three proportional concentrations of cultivated substrate and cement were also prioritized to gather results of variation focused on the weights of the bricks in the Water Absorption Test and Durability Test. Fungal inoculums with solutions of cement showed small to moderate amounts of decrease and increase in load. This proves that the treatments did not show any significant difference when it comes to strength, efficiency and absorption capacity. Each of the concentration is equally valid and could be used in supporting the worldwide demands of creating numerous bricks while also taking into consideration the recovery of our nature.

Keywords: mycelium, fungi, fungal mycelia, durability test, water absorption test

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7 Spatial Distribution and Cluster Analysis of Sexual Risk Behaviors and STIs Reported by Chinese Adults in Guangzhou, China: A Representative Population-Based Study

Authors: Fangjing Zhou, Wen Chen, Brian J. Hall, Yu Wang, Carl Latkin, Li Ling, Joseph D. Tucker

Abstract:

Background: Economic and social reforms designed to open China to the world has been successful, but also appear to have rapidly laid the foundation for the reemergence of STIs since 1980s. Changes in sexual behaviors, relationships, and norms among Chinese contributed to the STIs epidemic. As the massive population moved during the last 30 years, early coital debut, multiple sexual partnerships, and unprotected sex have increased within the general population. Our objectives were to assess associations between residences location, sexual risk behaviors and sexually transmitted infections (STIs) among adults living in Guangzhou, China. Methods: Stratified cluster sampling followed a two-step process was used to select populations aged 18-59 years in Guangzhou, China. Spatial methods including Geographic Information Systems (GIS) were utilized to identify 1400 coordinates with latitude and longitude. Face-to-face household interviews were conducted to collect self-report data on sexual risk behaviors and diagnosed STIs. Kulldorff’s spatial scan statistic was implemented to identify and detect spatial distribution and clusters of sexual risk behaviors and STIs. The presence and location of statistically significant clusters were mapped in the study areas using ArcGIS software. Results: In this study, 1215 of 1400 households attempted surveys, with 368 refusals, resulting in a sample of 751 completed surveys. The prevalence of self-reported sexual risk behaviors was between 5.1% and 50.0%. The self-reported lifetime prevalence of diagnosed STIs was 7.06%. Anal intercourse clustered in an area located along the border within the rural-urban continuum (p=0.001). High rate clusters for alcohol or other drugs using before sex (p=0.008) and migrants who lived in Guangzhou less than one year (p=0.007) overlapped this cluster. Excess cases for sex without a condom (p=0.031) overlapped the cluster for college students (p<0.001). Conclusions: Short-term migrants and college students reported greater sexual risk behaviors. Programs to increase safer sex within these communities to reduce the risk of STIs are warranted in Guangzhou. Spatial analysis identified geographical clusters of sexual risk behaviors, which is critical for optimizing surveillance and targeting control measures for these locations in the future.

Keywords: cluster analysis, migrant, sexual risk behaviors, spatial distribution

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6 Faculty Use of Geospatial Tools for Deep Learning in Science and Engineering Courses

Authors: Laura Rodriguez Amaya

Abstract:

Advances in science, technology, engineering, and mathematics (STEM) are viewed as important to countries’ national economies and their capacities to be competitive in the global economy. However, many countries experience low numbers of students entering these disciplines. To strengthen the professional STEM pipelines, it is important that students are retained in these disciplines at universities. Scholars agree that to retain students in universities’ STEM degrees, it is necessary that STEM course content shows the relevance of these academic fields to their daily lives. By increasing students’ understanding on the importance of these degrees and careers, students’ motivation to remain in these academic programs can also increase. An effective way to make STEM content relevant to students’ lives is the use of geospatial technologies and geovisualization in the classroom. The Geospatial Revolution, and the science and technology associated with it, has provided scientists and engineers with an incredible amount of data about Earth and Earth systems. This data can be used in the classroom to support instruction and make content relevant to all students. The purpose of this study was to find out the prevalence use of geospatial technologies and geovisualization as teaching practices in a USA university. The Teaching Practices Inventory survey, which is a modified version of the Carl Wieman Science Education Initiative Teaching Practices Inventory, was selected for the study. Faculty in the STEM disciplines that participated in a summer learning institute at a 4-year university in the USA constituted the population selected for the study. One of the summer learning institute’s main purpose was to have an impact on the teaching of STEM courses, particularly the teaching of gateway courses taken by many STEM majors. The sample population for the study is 97.5 of the total number of summer learning institute participants. Basic descriptive statistics through the Statistical Package for the Social Sciences (SPSS) were performed to find out: 1) The percentage of faculty using geospatial technologies and geovisualization; 2) Did the faculty associated department impact their use of geospatial tools?; and 3) Did the number of years in a teaching capacity impact their use of geospatial tools? Findings indicate that only 10 percent of respondents had used geospatial technologies, and 18 percent had used geospatial visualization. In addition, the use of geovisualization among faculty of different disciplines was broader than the use of geospatial technologies. The use of geospatial technologies concentrated in the engineering departments. Data seems to indicate the lack of incorporation of geospatial tools in STEM education. The use of geospatial tools is an effective way to engage students in deep STEM learning. Future research should look at the effect on student learning and retention in science and engineering programs when geospatial tools are used.

Keywords: engineering education, geospatial technology, geovisualization, STEM

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5 Nature Manifestations: An Archetypal Analysis of Selected Nightwish Songs

Authors: Suzanne Strauss, Leandi Steenkamp

Abstract:

The Finnish symphonic metal band Nightwish is the brainchild of songwriter and lyricist TuomasHolopainen and the band recorded their first demonstration recording in 1996. The band has since produced nine full-length studio albums, the most recent being the 2020 album Human. :||: Nature., and has reached massive international success. The band is well known for songs about fantasy and escapism and employs many sonic, visual and branding tools and techniques to communicate these constructs to the audience. Among these, is the band’s creation of the so-called “Nightwish world and mythology” with a set of recurring characters and narratives which, in turn, creates a psychological anchor and safe space for Nightwish fans around the globe. Nature and the reverence of nature are central themes in Nightwish’s self-created mythology.Swiss psychologist Carl Jung’s theory of the collective unconscious identified a mysterious reservoir of psychological constructs common to all people, being derived from ancestral memory and experience, common to all humankind, and distinct from the individual’s personal unconscious. Furthermore, he defined archetypes as timeless collective patterns and images that springs forth from the collective unconscious. Archetypes can be actualized when they enter consciousness as images in interaction with the outside world. Archetypal patterns or images can manifest in different ways across world cultures, but follow common patterns, also known as archetypal themes and symbols. The Jungian approach to the psyche places great emphasis on nature, positing a direct link betweenthe concept of wholeness and responsible care for nature and the environment.In our proposed paper, we examine, by means of thematic content analysis, how Nightwish makes use of archetypal themes and symbols referring to nature and the environment in selected songs from their ninth full-length album Human. II Nature. Furthermore, we argue that the longing for and reverence of nature in selected Nightwish songs may serve as a type of “social intervention” and social critique on modern capitalist society. The type of social critique that the band offers is generally connoted intertextually and is not equally explicit in their songs. The band uses a unique combination of escapism, fantasy, and nature narratives to inspire a sense of wonder, enchantment, and magic in the listener. In this way, escapism, fantasy, and nature serve as postmodern frames of reference that aim to “re-enchant” the disenchanted and de-spiritualized. In this way, re-enchantment could also refer to spiritual and/or psychological healing and rebirth.

Keywords: archetypes, metal music, nature, Nightwish, social interventions

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4 Exploring the Lived Experiences of Breast Cancer Survivors Post-Treatment

Authors: Nova Grail S. Luminang, Gwyneth B. Gortiza, Alvin E. Haboc, Marinol K. Hate, Rhean Mitchel N. Joven, Kara Kate D. Lammao, Rosemarie M. Lambayung, Elmo Carl D. Lardizabal, Zyra B. Linggayo, Rizza Mae G. Liwag, Ronalyn O. Songcuan

Abstract:

Breast cancer survivorship represents a complex and continuous journey extending beyond the completion of treatment, involving coping with physical, emotional, and psychological aspects of life post-treatment. This study aimed to explore the lived experiences of breast cancer survivors after successful treatment in Tabuk City, focusing on their post-treatment experiences, coping mechanisms, and necessary lifestyle changes. Researchers have selected Tabuk City as their research locale. Utilizing Martin Heidegger’s descriptive phenomenological design, this qualitative research included six participants, allowing for data saturation. Purposive sampling was employed to select participants. Researchers used Colaizzi’s Phenomenological Method in analyzing the data in order to achieve a reliable understanding of the participants’ experiences. The findings revealed three main themes: going through post-treatment hurdles, building resilience, and transformative wellness adjustments. Breast cancer survivors faced significant challenges, including physical adversities, emotional turmoil, limited social life, memory lapses, decreased sexual intimacy, and economic constraints. To cope, survivors adjusted their thoughts and attitudes, accepted their situation, relied on religious beliefs, and joined the support group Kalinga Cancer Care Ministry INC. Additionally, they strived to return to a normal life and embraced gratitude. Survivors made essential changes to their daily routines, modifying their diets, exploring herbal remedies, and incorporating physical activities such as walking and household chores. These adjustments helped improve their overall well-being and prevent cancer recurrence. The researchers concluded that the journey of breast cancer survivors is marked by significant challenges and inspiring resilience. The impact of breast cancer treatment extends beyond physical recovery, encompassing profound emotional and social dimensions. Despite these difficulties, survivors demonstrate remarkable strength and adaptability, making positive lifestyle changes that offer a hopeful and inspiring narrative of recovery and perseverance.

Keywords: breast cancer, lived experiences, breast cancer survivor, post-treatment hurdles, emotional turmoil

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3 Characteristics of Bio-hybrid Hydrogel Materials with Prolonged Release of the Model Active Substance as Potential Wound Dressings

Authors: Katarzyna Bialik-Wąs, Klaudia Pluta, Dagmara Malina, Małgorzata Miastkowska

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In recent years, biocompatible hydrogels have been used more and more in medical applications, especially as modern dressings and drug delivery systems. The main goal of this research was the characteristics of bio-hybrid hydrogel materials incorporated with the nanocarrier-drug system, which enable the release in a gradual and prolonged manner, up to 7 days. Therefore, the use of such a combination will provide protection against mechanical damage and adequate hydration. The proposed bio-hybrid hydrogels are characterized by: transparency, biocompatibility, good mechanical strength, and the dual release system, which allows for gradual delivery of the active substance, even up to 7 days. Bio-hybrid hydrogels based on sodium alginate (SA), poly(vinyl alcohol) (PVA), glycerine, and Aloe vera solution (AV) were obtained through the chemical crosslinking method using poly(ethylene glycol) diacrylate as a crosslinking agent. Additionally, a nanocarrier-drug system was incorporated into SA/PVA/AV hydrogel matrix. Here, studies were focused on the release profiles of active substances from bio-hybrid hydrogels using the USP4 method (DZF II Flow-Through System, Erweka GmbH, Langen, Germany). The equipment incorporated seven in-line flow-through diffusion cells. The membrane was placed over support with an orifice of 1,5 cm in diameter (diffusional area, 1.766 cm²). All the cells were placed in a cell warmer connected with the Erweka heater DH 2000i and the Erweka piston pump HKP 720. The piston pump transports the receptor fluid via seven channels to the flow-through cells and automatically adapts the setting of the flow rate. All volumes were measured by gravimetric methods by filling the chambers with Milli-Q water and assuming a density of 1 g/ml. All the determinations were made in triplicate for each cell. The release study of the model active substance was carried out using a regenerated cellulose membrane Spectra/Por®Dialysis Membrane MWCO 6-8,000 Carl Roth® Company. These tests were conducted in buffer solutions – PBS at pH 7.4. A flow rate of receptor fluid of about 4 ml /1 min was selected. The experiments were carried out for 7 days at a temperature of 37°C. The released concentration of the model drug in the receptor solution was analyzed using UV-Vis spectroscopy (Perkin Elmer Company). Additionally, the following properties of the modified materials were studied: physicochemical, structural (FT-IR analysis), morphological (SEM analysis). Finally, the cytotoxicity tests using in vitro method were conducted. The obtained results exhibited that the dual release system allows for the gradual and prolonged delivery of the active substances, even up to 7 days.

Keywords: wound dressings, SA/PVA hydrogels, nanocarrier-drug system, USP4 method

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2 Women's Perceptions of Zika Virus Prevention Recommendations: A Tale of Two Cities within Fortaleza, Brazil

Authors: Jeni Stolow, Lina Moses, Carl Kendall

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Zika virus (ZIKV) reemerged as a global threat in 2015 with Brazil at its epicenter. Brazilians have a long history of combatting Aedes aegypti mosquitos as it is a common vector for dengue, chikungunya, and yellow fever. As a response to the epidemic, public health authorities promoted ZIKV prevention behaviors such as mosquito bite prevention, reproductive counseling for women who are pregnant or contemplating pregnancy, pregnancy avoidance, and condom use. Most prevention efforts from Brazil focused on the mosquito vector- utilizing recycled dengue approaches without acknowledging the context in which women were able to adhere to these prevention messages. This study used qualitative methods to explore how women in Fortaleza, Brazil perceive ZIKV, the Brazilian authorities’ ZIKV prevention recommendations, and the feasibility of adhering to these recommendations. A core study aim was to look at how women perceive their physical, social, and natural environment as it impacts women’s ability to adhere to ZIKV prevention behaviors. A Rapid Anthropological Assessment (RAA) containing observations, informational interviews, and semi-structured in-depth interviews were utilized for data collection. The study utilized Grounded Theory as the systematic inductive method of analyzing the data collected. Interviews were conducted with 35 women of reproductive age (15-39 years old), who primarily utilize the public health system. It was found that women’s self-identified economic class was associated with how strongly women felt they could prevent ZIKV. All women interviewed technically belong to the C-class, the middle economic class. Although all members of the same economic class, there was a divide amongst participants as to who perceived themselves as higher C-class versus lower C-class. How women saw their economic status was dictated by how they perceived their physical, social, and natural environment. Women further associated their environment and their economic class to their likelihood of contracting ZIKV, their options for preventing ZIKV, their ability to prevent ZIKV, and their willingness to attempt to prevent ZIKV. Women’s perceived economic status was found to relate to their structural environment (housing quality, sewage, and locations to supplies), social environment (family and peer norms), and natural environment (wetland areas, natural mosquito breeding sites, and cyclical nature of vectors). Findings from this study suggest that women’s perceived environment and economic status impact their perceived feasibility and desire to attempt behaviors to prevent ZIKV. Although ZIKV has depleted from epidemic to endemic status, it is suggested that the virus will return as cyclical outbreaks like that seen with similar arboviruses such as dengue and chikungunya. As the next ZIKV epidemic approaches it is essential to understand how women perceive themselves, their abilities, and their environments to best aid the prevention of ZIKV.

Keywords: Aedes aegypti, environment, prevention, qualitative, zika

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1 Computational Approaches to Study Lineage Plasticity in Human Pancreatic Ductal Adenocarcinoma

Authors: Almudena Espin Perez, Tyler Risom, Carl Pelz, Isabel English, Robert M. Angelo, Rosalie Sears, Andrew J. Gentles

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies. The role of the tumor microenvironment (TME) is gaining significant attention in cancer research. Despite ongoing efforts, the nature of the interactions between tumors, immune cells, and stromal cells remains poorly understood. The cell-intrinsic properties that govern cell lineage plasticity in PDAC and extrinsic influences of immune populations require technically challenging approaches due to the inherently heterogeneous nature of PDAC. Understanding the cell lineage plasticity of PDAC will improve the development of novel strategies that could be translated to the clinic. Members of the team have demonstrated that the acquisition of ductal to neuroendocrine lineage plasticity in PDAC confers therapeutic resistance and is a biomarker of poor outcomes in patients. Our approach combines computational methods for deconvolving bulk transcriptomic cancer data using CIBERSORTx and high-throughput single-cell imaging using Multiplexed Ion Beam Imaging (MIBI) to study lineage plasticity in PDAC and its relationship to the infiltrating immune system. The CIBERSORTx algorithm uses signature matrices from immune cells and stroma from sorted and single-cell data in order to 1) infer the fractions of different immune cell types and stromal cells in bulked gene expression data and 2) impute a representative transcriptome profile for each cell type. We studied a unique set of 300 genomically well-characterized primary PDAC samples with rich clinical annotation. We deconvolved the PDAC transcriptome profiles using CIBERSORTx, leveraging publicly available single-cell RNA-seq data from normal pancreatic tissue and PDAC to estimate cell type proportions in PDAC, and digitally reconstruct cell-specific transcriptional profiles from our study dataset. We built signature matrices and optimized by simulations and comparison to ground truth data. We identified cell-type-specific transcriptional programs that contribute to cancer cell lineage plasticity, especially in the ductal compartment. We also studied cell differentiation hierarchies using CytoTRACE and predict cell lineage trajectories for acinar and ductal cells that we believe are pinpointing relevant information on PDAC progression. Collaborators (Angelo lab, Stanford University) has led the development of the Multiplexed Ion Beam Imaging (MIBI) platform for spatial proteomics. We will use in the very near future MIBI from tissue microarray of 40 PDAC samples to understand the spatial relationship between cancer cell lineage plasticity and stromal cells focused on infiltrating immune cells, using the relevant markers of PDAC plasticity identified from the RNA-seq analysis.

Keywords: deconvolution, imaging, microenvironment, PDAC

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