Search results for: tissue engineered aortic heart valve

Authors: K. O’Mara, T. Cresswell

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Nearly half of the world’s population live near the coast, and as a result, estuaries and coastal bays in populated or industrialized areas often receive metal pollution. Heavy metals have a chemical affinity for sediment particles and can be stored in estuarine sediments and become biologically available under changing conditions. Organisms inhabiting estuaries can be exposed to metals from a variety of sources including metals dissolved in water, bound to sediment or within contaminated prey. Metal uptake and assimilation responses can vary even between species that are biologically similar, making pollution effects difficult to predict. A multi-trophic level experiment representing a common Eastern Australian estuarine food chain was used to study the sources for Cd, Mn and Zn uptake and assimilation in organisms occupying several trophic levels. Sand cockles (Katelysia scalarina), school prawns (Metapenaeus macleayi) and sand whiting (Sillago ciliata) were exposed to radiolabelled seawater, suspended sediment and food. Three pulse-chase trials on filter-feeding sand cockles were performed using radiolabelled phytoplankton (Tetraselmis sp.), benthic microalgae (Entomoneis sp.) and suspended sediment. Benthic microalgae had lower metal uptake than phytoplankton during labelling but higher cockle assimilation efficiencies (Cd = 51%, Mn = 42%, Zn = 63 %) than both phytoplankton (Cd = 21%, Mn = 32%, Zn = 33%) and suspended sediment (except Mn; (Cd = 38%, Mn = 42%, Zn = 53%)). Sand cockles were also sensitive to uptake of Cd, Mn and Zn dissolved in seawater. Uptake of these metals from the dissolved phase was negligible in prawns and fish, with prawns only accumulating metals during moulting, which were then lost with subsequent moulting in the depuration phase. Diet appears to be the main source of metal assimilation in school prawns, with 65%, 54% and 58% assimilation efficiencies from Cd, Mn and Zn respectively. Whiting fed contaminated prawns were able to exclude the majority of the metal activity through egestion, with only 10%, 23% and 11% assimilation efficiencies from Cd, Mn and Zn respectively. The findings of this study support previous studies that find diet to be the dominant accumulation source for higher level trophic organisms. These results show that assimilation efficiencies can vary depending on the source of exposure; sand cockles assimilated more Cd, Mn, and Zn from the benthic diatom than phytoplankton and assimilation was higher in sand whiting fed prawns compared to artificial pellets. The sensitivity of sand cockles to metal uptake and assimilation from a variety of sources poses concerns for metal availability to predators ingesting the clam tissue, including humans. The high tolerance of sand whiting to these metals is reflected in their widespread presence in Eastern Australian estuaries, including contaminated estuaries such as Botany Bay and Port Jackson.

Keywords: cadmium, food chain, metal, manganese, trophic, zinc

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Authors: M. A. Rahman, A. T. Ohta, H. V. Trinh, J. Hyvl

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Atmospheric pressure and oxygen (O2) concentration are critical life support parameters for human-occupied aerospace vehicles and habitats. Various medical conditions may require medical O2; for example, the American Medical Association has determined that commercial air travel exposes passengers to altitude-related hypoxia and gas expansion. It may cause some passengers to experience significant symptoms and medical complications during the flight, requiring supplemental medical-grade O2 to maintain adequate tissue oxygenation and prevent hypoxemic complications. Although supplemental medical grade O2 is a successful lifesaver for respiratory and cardiac failure, O2-enriched exhaled air can contain more than 95 % O2, increasing the likelihood of a fire. In an aerospace environment, a localized high concentration O2 bubble forms around a patient being treated for hypoxia, increasing the cabin O2 beyond the safe limit. To address this problem, this work describes a medical O2 delivery system that can reduce the O2 concentration from patient-exhaled O2-rich air to safe levels while maintaining the prescribed O2 administration to the patient. The O2 delivery system is designed to be a part of the medical O2 kit. The system uses cationic multimetallic cobalt complexes to reversibly, selectively, and stoichiometrically chemisorb O2 from the exhaled air. An air-release sub-system monitors the exhaled air, and as soon the O2 percentage falls below 21%, the air is released to the room air. The O2-enriched exhaled air is channeled through a layer of porous, thin-film heaters coated with the cobalt complex. The complex absorbs O2, and when saturated, the complex is heated to 100°C using the thin-film heater. Upon heating, the complex desorbs O2 and is once again ready to absorb or remove the excess O2 from exhaled air. The O2 absorption is a sub-second process, and desorption is a multi-second process. While heating at 0.685 °C/sec, the complex desorbs ~90% O2 in 110 sec. These fast reaction times mean that a simultaneous absorb/desorb process in the O2 delivery system will create a continuous absorption of O2. Moreover, the complex can concentrate O2 by a factor of 160 times that in air and desorb over 90% of the O2 at 100°C. Over 12 cycles of thermogravimetry measurement, less than 0.1% decrease in reversibility in O2 uptake was observed. The 1 kg complex can desorb over 20L of O2, so simultaneous O2 desorption by 0.5 kg of complex and absorption by 0.5 kg of complex can potentially continuously remove 9L/min O2 (~90% desorbed at 100°C) from exhaled air. The complex is synthesized and characterized for reversible O2 absorption and efficacy. The complex changes its color from dark brown to light gray after O2 desorption. In addition to thermogravimetric analysis, the O2 absorption/desorption cycle is characterized using optical imaging, showing stable color changes over ten cycles. The complex was also tested at room temperature in a low O2 environment in its O2 desorbed state, and observed to hold the deoxygenated state under these conditions. The results show the feasibility of using the complex for reversible O2 absorption in the proposed fire safe medical O2 delivery system.

Keywords: fire risk, medical oxygen, oxygen removal, reversible absorption

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Authors: Aoxue Yang, Weili Tian, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Glucocorticoids (GCs) are used to treat GBM-associated edema. However, glucocorticoids participate in the physiological response to psychosocial stress, linked to poor cancer prognosis. This raises concern that glucocorticoids affect the tumor and BTSCs. Identifying markers specifically expressed by brain tumor stem cells (BTSCs) may enable specific therapies that spare their regular tissue-resident counterparts. By ribosome profiling analysis, we have identified that glycerol-3-phosphate dehydrogenase 1 (GPD1) is expressed by dormant BTSCs but not by NSCs. Through different stress-induced experiments in vitro, we found that only dexamethasone (DEXA) can significantly increase the expression of GPD1 in NSCs. Adversely, mifepristone (MIFE) which is classified as glucocorticoid receptors antagonists, could decrease GPD1 protein level and weaken the proliferation and stemness in BTSCs. Furthermore, DEXA can induce GPD1 expression in tumor-bearing mice brains and shorten animal survival, whereas MIFE has a distinct adverse effect that prolonged mice lifespan. Knocking out GR in NSC can block the upregulation of GPD1 inducing by DEXA, and we find the specific sequences on GPD1 promotor combined with GR, thus improving the efficiency of GPD1 transcription from CHIP-Seq. Moreover, GR and GPD1 are highly co-stained on GBM sections obtained from patients and mice. All these findings confirmed that GR could regulate GPD1 and loss of GPD1 Impairs Multiple Pathways Important for BTSCs Maintenance GPD1 is also a critical enzyme regulating glycolysis and lipid synthesis. We observed that DEXA and MIFE could change the metabolic profiles of BTSCs by regulating GPD1 to shift the transition of cell dormancy. Our transcriptome and lipidomics analysis demonstrated that cell cycle signaling and phosphoglycerides synthesis pathways contributed a lot to the inhibition of GPD1 caused by MIFE. In conclusion, our findings raise concern that treatment of GBM with GCs may compromise the efficacy of chemotherapy and contribute to BTSC dormancy. Inhibition of GR can dramatically reduce GPD1 and extend the survival duration of GBM-bearing mice. The molecular link between GPD1 and GR may give us an attractive therapeutic target for glioblastoma.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides

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Authors: Abir Soltani, Moez Amri, Jouda Mediouni Ben Jemâa

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In North Africa, the chickpea leafminer Liriomyza cicerina (Rondani) (Diptera: Agromizidae) is one of the major damaging pests affecting both spring and winter-planted chickpea. Damage is caused by the larvae which feed in the leaf mesophyll tissue, resulting in desiccation and premature leaf fall that can cause severe yield losses. In the present work, the distribution and the seasonal phenology of L. cicerina were studied on two chickpea varieties; a winter variety Beja 1 which is the most cultivated variety in Tunisia and a spring-sown variety Amdoun 1. The experiment was conducted during the cropping season 2015-2016. In the experimental research station Oued Beja, in the Beja region (36°44’N; 9°13’E). To determine the distribution and seasonal phenology of L. cicerina in both studied varieties Beja 1 and Amdoun 1, respectively 100 leave samples (50 from the top and 50 from the base) were collected from 10 chickpea plants randomly chosen from each field. The sampling was done during three development stages (i) 20-25 days before flowering (BFL), (ii) at flowering (FL) and (ii) at pod setting stage (PS). For each plant, leaves were checked from the base till the upper ones for the insect infestation progress into the plant in correlation with chickpea growth Stages. Fly adult populations were monitored using 8 yellow sticky traps together with weekly leaves sampling in each field. The traps were placed 70 cm above ground. Trap catches were collected once a week over the cropping season period. Results showed that L. cicerina distribution varied among both studied chickpea varieties and crop development stage all with seasonal phenology. For the winter chickpea variety Beja 1, infestation levels of 2%, 10.3% and 20.3% were recorded on the bases plant part for BFL, FL and PS stages respectively against 0%, 8.1% and 45.8% recorded for the upper plant part leaves for the same stages respectively. For the spring-sown variety Amdoun 1 the infestation level reached 71.5% during flowering stage. Population dynamic study revealed that for Beja 1 variety, L. cicerina accomplished three annual generations over the cropping season period with the third one being the most important with a capture level of 85 adult/trap by mid-May against a capture level of 139 adult/trap at the end May recorded for cv. Amdoun 1. Also, results showed that L. cicerina field infestation dispersal depends on the field part and on the crop growth stage. The border areas plants were more infested than the plants placed inside the plots. For cv. Beja 1, border areas infestations were 11%, 28% and 91.2% for BFL, FL and PS stages respectively, against 2%, 10.73% and 69.2% recorded on the on the inside plot plants during the for the same growth stages respectively. For the cv. Amdoun1 infestation level of 90% was observed on the border plants at FL and PS stages against an infestation level less than 65% recorded inside the plot.

Keywords: leaf miner, liriomyza cicerina, chickpea, distribution, seasonal phenology, Tunisia

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Authors: Tsirekidze M., Aprasidze T.

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Introduction: The problem of dissocial behavior is at the heart of the social sciences and psychiatry; however, it should be noted that its psychiatric aspect is little studied, and some issues of the problem are still controversial. This is complicated by the diversity of terminological concepts in defining “dissocial behavior”, “behavioral disorder”, “abnormal behavior”, “deviant behavior”, “delinquent behavior”, etc. In literature, there is no comprehensive definition of the essence of dissociative behavior. Numerous attempts to systematize dissociative disorders should also be considered unsatisfactory, which is primarily related to the lack of solid criteria for defining this group of disorders. According to the clinical classification, dissocial behavior is divided into psychotic and non-psychotic forms. Such differentiation is conditional in nature since it is not always possible to draw precise, clear distinctions between these forms, and in addition, there is a transition of a behavior disorder or so-called intermediate forms. One group of authors distinguishes two main forms of deviant behavior in terms of both theoretical and practical significance - non-pathological and pathological. In recent years, especially, the non-pathological form of behavior disorder has become topical. It refers to a large group of forms of deviant behavior, the emergence of which is associated with psychologically full-fledged reactions of children and adolescents to stressful situations and extreme conditions. According to the authors, its concept is understandable-it is difficult to draw a line between psychologically understandable reactions and psychogenically induced reactive states. In addition, the concept of "normal" child and adolescent is, to some extent, a vague concept, as in medicine, any definition of the norm. From a practical (more precisely, pragmatic) point of view, the term "abnormal behavioral disorder" undoubtedly makes sense, especially for the purpose of forensic psychiatric examination. Non-pathological deviation mainly includes transient situational reactions, microsocial-pedagogical backwardness, and character accentuation.Deviant behavior was predominantly manifested in a non-pathological form, which, in our opinion, is due to the difficult socio-economic situation of the country, moral-ethical deprivation, and expressed frustration. By itself, society is an indicator of deviation. Add to this situation complicated factors such as micro-social-pedagogical leave, unfavorable family environment, and parenting defects. Consideration is also given to the connection of acceptable deviation with the personal structural features of the adolescent. Aim: The topic of our discussion is the dissocial behavior of the non-psychotic register. Methods: We surveyed 120 adolescents with deviant behaviors. 61% of them were diagnosed with various neuropsychiatric disorders. Results: Abnormal forms of deviant behavior were observed in 13%, and non-pathological forms in -69%. A combination of non-pathological and pathological forms was present in 10% of cases. In the case of non-pathological deviation, microsocial-pedagogical acceptance was revealed in 62%, character accentuation in 22%; during the pathological forms, pathological reactions were observed in 21%, and abnormal formation of the person -21%. Conclusion: It should be emphasized that in case of any of the above defects, if the so-called family psychosis, and medical and pedagogical habilitation measures for the adolescent, it is quite possible to prevent the abnormal development of the child's personality, correct his character, regulate behavior and develop positive labor-social relations.

Keywords: dissocial personality, deviant behavior, dissocial, delinquent behavior

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Authors: Tiziana Ferrero-Regis, Marissa Lindquist

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Circular Economy (CE) is increasingly seen as the reorganisation of production and consumption, and cities are acknowledged as the sources of many ecological and social problems; at the same time, they can be re-imagined through an ecologically and socially resilient future. The concept of the CE has received pointed critiques for its techno-deterministic orientation, focus on science and transformation by the policy. At the heart of our local re-imagining of the CE into circularity through contact zones there is the acknowledgment of collective, spontaneous and shared imaginations of alternative and sustainable futures through the creation of networks of community initiatives that are transformative, creating opportunities that simultaneously make cities rich and enrich humans. This paper presents a mapping project of the fashion and textile ecosystem in Brisbane, Queensland, Australia. Brisbane is currently the most aspirational city in Australia, as its population growth rate is the highest in the country. Yet, Brisbane is considered the least “fashion city” in the country. In contrast, the project revealed a greatly enhanced picture of distinct fashion and textile clusters across greater Brisbane and the adjacency of key services that may act to consolidate CE community contact zones. Clusters to the north of Brisbane and several locales to the south are zones of a greater mix between public/social amenities, walkable zones and local transport networks with educational precincts, community hubs, concentration of small enterprises, designers, artisans and waste recovery centers that will help to establish knowledge of key infrastructure networks that will support enmeshing these zones together. The paper presents two case studies of independent designers who work on new and re-designed clothing through recovering pre-consumer textiles and that operate from within creative precincts. The first case is designer Nelson Molloy, who recently returned to the inner city suburb of West End with their Chasing Zero Design project. The area was known in the 1980s and 1990s for its alternative lifestyle with creative independent production, thrifty clothing shops, alternative fashion and a socialist agenda. After 30 years of progressive gentrification of the suburb, which has dislocated many of the artists, designers and artisans, West End is seeing the return and amplification of clusters of artisans, artists, designers and architects. The other case study is Practice Studio, located in a new zone of creative growth, Bowen Hills, north of the CBD. Practice Studio combines retail with a workroom, offers repair and remaking services, becoming a point of reference for young and emerging Australian designers and artists. The paper demonstrates the spatial politics of the CE and the way in which new cultural capital is produced thanks to cultural specificities and resources. It argues for the recognition of contact zones that are created by local actors, communities and knowledge networks, whose grass-roots agency is fundamental for the co-production of CE’s systems of local governance.

Keywords: contact zones, circular citities, fashion and textiles, circular neighbourhoods, australia

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Authors: C. Sancho Salvatierra, J. M. Martinez Nieto, R. García Gonzalez-Gordon, M. I. Martinez Bellido

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Introduction: Nature could act as an asset for human health protecting against possible diseases and promoting the state of both physical and mental health. Goals: This paper aims to determine which natural elements present evidence that show positive influence on human health, on which particular aspects and how. It also aims to determine the best biomarkers to measure such influence. Method: A systematic literature review was carried out. First, a general free text search was performed in databases, such as Scopus, PubMed or PsychInfo. Secondly, a specific search was performed combining keywords in order of increasing complexity. Also the Snowballing technique was used and it was consulted in the CSIC’s (The Spanish National Research Council). Databases: Of the 130 articles obtained and reviewed, 80 referred to natural elements that influenced health. These 80 articles were classified and tabulated according to the nature elements found, the health aspects studied, the health measurement parameters used and the measurement techniques used. In this classification the results of the studies were codified according to whether they were positive, negative or neutral both for the elements of nature and for the aspects of health studied. Finally, the results of the 80 selected studies were summarized and categorized according to the elements of nature that showed the greatest positive influence on health and the biomarkers that had shown greater reliability to measure said influence. Results: Of the 80 articles studied, 24 (30.0%) were reviews and 56 (70.0%) were original research articles. Among the 24 reviews, 18 (75%) found positive results of natural elements on health, and 6 (25%) both positive and negative effects. Of the 56 original articles, 47 (83.9%) showed positive results, 3 (5.4%) both positive and negative, 4 (7.1%) negative effects, and 2 (3.6%) found no effects. The results reflect positive effects of different elements of nature on the following pathologies: diabetes, high blood pressure, stress, attention deficit hyperactivity disorder, psychotic, anxiety and affective disorders. They also show positive effects on the following areas: immune system, social interaction, recovery after illness, mood, decreased aggressiveness, concentrated attention, cognitive performance, restful sleep, vitality and sense of well-being. Among the elements of nature studied, those that show the greatest positive influence on health are forest immersion, natural views, daylight, outdoor physical activity, active transport, vegetation biodiversity, natural sounds and the green residences. As for the biomarkers used that show greater reliability to measure the effects of natural elements are the levels of cortisol (both in blood and saliva), vitamin D levels, serotonin and melatonin, blood pressure, heart rate, muscle tension and skin conductance. Conclusions: Nature is an asset for health, well-being and quality of life. Awareness programs, education and health promotion are needed based on the elements that nature brings us, which in turn generate proactive attitudes in the population towards the protection and conservation of nature. The studies related to this subject in Spain are very scarce. Aknowledgements. This study has been promoted and partially financed by the Environmental Foundation Jaime González-Gordon.

Keywords: health, green areas, nature, well-being

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Authors: Ren-Jy Ben, Jo-Chi Jao, Chiu-Ya Liao, Ya-Ru Tsai, Lain-Chyr Hwang, Po-Chou Chen

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Cancer is still one of the serious diseases threatening the lives of human beings. How to have an early diagnosis and effective treatment for tumors is a very important issue. The animal carcinoma model can provide a simulation tool for the study of pathogenesis, biological characteristics and therapeutic effects. Recently, drug delivery systems have been rapidly developed to effectively improve the therapeutic effects. Liposome plays an increasingly important role in clinical diagnosis and therapy for delivering a pharmaceutic or contrast agent to the targeted sites. Liposome can be absorbed and excreted by the human body, and is well known that no harm to the human body. This study aimed to compare the therapeutic effects between encapsulated (doxorubicin liposomal, LipoDox) and un-encapsulated (doxorubicin, Dox) anti-tumor drugs using Magnetic Resonance Imaging (MRI). Twenty-four New Zealand rabbits implanted with VX2 carcinoma at left thigh were classified into three groups: control group (untreated), Dox-treated group and LipoDox-treated group, 8 rabbits for each group. MRI scans were performed three days after tumor implantation. A 1.5T GE Signa HDxt whole body MRI scanner with a high resolution knee coil was used in this study. After a 3-plane localizer scan was performed, Three-Dimensional (3D) Fast Spin Echo (FSE) T2-Weighted Images (T2WI) was used for tumor volumetric quantification. And Two-Dimensional (2D) spoiled gradient recalled echo (SPGR) dynamic Contrast-enhanced (DCE) MRI was used for tumor perfusion evaluation. DCE-MRI was designed to acquire four baseline images, followed by contrast agent Gd-DOTA injection through the ear vein of rabbits. Afterwards, a series of 32 images were acquired to observe the signals change over time in the tumor and muscle. The MRI scanning was scheduled on a weekly basis for a period of four weeks to observe the tumor progression longitudinally. The Dox and LipoDox treatments were prescribed 3 times in the first week immediately after VX2 tumor implantation. ImageJ was used to quantitate tumor volume and time course signal enhancement on DCE images. The changes of tumor size showed that the growth of VX2 tumors was effectively inhibited for both LipoDox-treated and Dox-treated groups. Furthermore, the tumor volume of LipoDox-treated group was significantly lower than that of Dox-treated group, which implies that LipoDox has better therapeutic effect than Dox. The signal intensity of LipoDox-treated group is significantly lower than that of the other two groups, which implies that targeted therapeutic drug remained in the tumor tissue. This study provides a radiation-free and non-invasive MRI method for therapeutic monitoring of targeted liposome on an animal tumor model.

Keywords: doxorubicin, dynamic contrast-enhanced MRI, lipodox, magnetic resonance imaging, VX2 tumor model

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Authors: Antonela Matana, Dubravka Brdar, Vesela Torlak, Marijana Popovic, Ivana Gunjaca, Ozren Polasek, Vesna Boraska Perica, Maja Barbalic, Ante Punda, Caroline Hayward, Tatijana Zemunik

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Parathyroid hormone (PTH) plays a critical role in the regulation of bone mineral metabolism and calcium homeostasis. Higher PTH levels are associated with heart failure, hypertension, coronary artery disease, cardiovascular mortality and poorer bone health. A twin study estimated that 60% of the variation in PTH concentrations is genetically determined. Only one GWAS of PTH concentration has been reported to date. Identified loci explained 4.5% of the variance in circulating PTH, suggesting that additional genetic variants remain undiscovered. Therefore, the aim of this study was to identify novel genetic variants associated with PTH levels in a general population. We have performed a GWAS meta-analysis on 2596 individuals originating from three Croatian cohorts: City of Split and the Islands of Korčula and Vis, within a large-scale project of “10,001 Dalmatians”. A total of 7 411 206 variants, imputed using the 1000 Genomes reference panel, with minor allele frequency ≥ 1% and Rsq ≥ 0.5 were analyzed for the association. GWAS within each data set was performed under an additive model, controlling for age, gender and relatedness. Meta-analysis was conducted using the inverse-variance fixed-effects method. Furthermore, to identify sex-specific effects, we have conducted GWAS meta-analyses analyzing males and females separately. In addition, we have performed biological pathway analysis. Four SNPs, representing one locus, reached genome-wide significance. The most significant SNP was rs11099476 on chromosome 4 (P=1.15x10-8), which explained 1.14 % of the variance in PTH. The SNP is located near the protein-coding gene RASGEF1B. Additionally, we detected suggestive association with SNPs, rs77178854 located on chromosome 2 in the DPP10 gene (P=2.46x10-7) and rs481121 located on chromosome 1 (P=3.58x10-7) near the GRIK1 gene. One of the top hits detected in the main meta-analysis, intron variant rs77178854 located within DPP10 gene, reached genome-wide significance in females (P=2.21x10-9). No single locus was identified in the meta-analysis in males. Fifteen biological pathways were functionally enriched at a P<0.01, including muscle contraction, ion homeostasis and cardiac conduction as the most significant pathways. RASGEF1B is the guanine nucleotide exchange factor, known to be associated with height, bone density, and hip. DPP10 encodes a membrane protein that is a member of the serine proteases family, which binds specific voltage-gated potassium channels and alters their expression and biophysical properties. In conclusion, we identified 2 novel loci associated with PTH levels in a general population, providing us with further insights into the genetics of this complex trait.

Keywords: general population, genome-wide association analysis, parathyroid hormone, single nucleotide polymorphisms.

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Authors: Huang Wei-Yi

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Objective: This article explores the intensive care nursing experience of a lung cancer patient with pulmonary embolism who was placed on ECMO. Following a sudden change in the patient’s condition and a consensus reached during a family meeting, the decision was made to withdraw life-sustaining equipment and collaborate with the palliative care team. Methods: The nursing period was from October 20 to October 27, 2023. The author monitored physiological data, observed, provided direct care, conducted interviews, performed physical assessments, and reviewed medical records. Together with the critical care team and bypass personnel, a comprehensive assessment was conducted using Gordon's Eleven Functional Health Patterns to identify the patient’s health issues, which included pain related to lung cancer and invasive devices, fear of death due to sudden deterioration, and altered tissue perfusion related to hemodynamic instability. Results: The patient was admitted with fever, back pain, and painful urination. During hospitalization, the patient experienced sudden discomfort followed by cardiac arrest, requiring multiple CPR attempts and ECMO placement. A subsequent CT angiogram revealed a pulmonary embolism. The patient's condition was further complicated by severe pain due to compression fractures, and a diagnosis of terminal lung cancer was unexpectedly confirmed, leading to emotional distress and uncertainty about future treatment. Throughout the critical care process, ECMO was removed on October 24, stabilizing the patient’s body temperature between 36.5-37°C and maintaining a mean arterial pressure of 60-80 mmHg. Pain management, including Morphine 8mg in 0.9% N/S 100ml IV drip q6h PRN and Ultracet 37.5 mg/325 mg 1# PO q6h, kept the pain level below 3. The patient was transferred to the ward on October 27 and discharged home on October 30. Conclusion: During the care period, collaboration with the medical team and palliative care professionals was crucial. Adjustments to pain medication, symptom management, and lung cancer-targeted therapy improved the patient’s physical discomfort and pain levels. By applying the unique functions of nursing and the four principles of palliative care, positive encouragement was provided. Family members, along with social workers, clergy, psychologists, and nutritionists, participated in cross-disciplinary care, alleviating anxiety and fear. The consensus to withdraw ECMO and life-sustaining equipment enabled the patient and family to receive high-quality care and maintain autonomy in decision-making. A follow-up call on November 1 confirmed that the patient was emotionally stable, pain-free, and continuing with targeted lung cancer therapy.

Keywords: intensive care, lung cancer, pulmonary embolism, ECMO

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Authors: M. I. Tyletc, O. I. Podgornya, T. G. Shaposhnikova, S. V. Shabelnikov, A. G. Mittenberg, M. A. Daugavet

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Ascidiacea is the most numerous class of the Tunicata subtype. These chordates' distinctive feature of the anatomical structure is a tunic consisting of cellulose fibrils, protein molecules, and single cells. The mechanisms of the tunic formation are not known in detail; tunic formation could be used as the model system for studying the interaction of cells with the extracellular matrix. Our model species is the ascidian Styela rustica, which is prevalent in benthic communities of the White Sea. As previously shown, the tunic formation involves morula blood cells, which contain the major 48 kDa protein p48. P48 participation in the tunic formation was proved using antibodies against the protein. The nature of the protein and its function remains unknown. The current research aims to determine the amino acid sequence of p48, as well as to clarify its role in the tunic formation. The peptides that make up the p48 amino acid sequence were determined by mass spectrometry. A search for peptides in protein sequence databases identified sequences homologous to p48 in Styela clava, Styela plicata, and Styela canopus. Based on sequence alignment, their level of similarity was determined as 81-87%. The correspondent sequence of ascidian Styela canopus was used for further analysis. The Styela rustica p48 sequence begins with a signal peptide, which could indicate that the protein is secretory. This is consistent with experimentally obtained data: the contents of morula cells secreted in the tunic matrix. The isoelectric point of p48 is 9.77, which is consistent with the experimental results of acid electrophoresis of morula cell proteins. However, the molecular weight of the amino acid sequence of ascidian Styela canopus is 103 kDa, so p48 of Styela rustica is a shorter homolog. The search for conservative functional domains revealed the presence of two Ca-binding EGF-like domains, thrombospondin (TSP1) and tyrosinase domains. The p48 peptides determined by mass spectrometry fall into the region of the sequence corresponding to the last two domains and have amino acid substitutions as compared to Styela canopus homolog. The tyrosinase domain (pfam00264) is known to be part of the phenoloxidase enzyme, which participates in melanization processes and the immune response. The thrombospondin domain (smart00209) interacts with a wide range of proteins, and is involved in several biological processes, including coagulation, cell adhesion, modulation of intercellular and cell-matrix interactions, angiogenesis, wound healing and tissue remodeling. It can be assumed that the tyrosinase domain in p48 plays the role of the phenoloxidase enzyme, and TSP1 provides a link between the extracellular matrix and cell surface receptors, and may also be responsible for the repair of the tunic. The results obtained are consistent with experimental data on p48. The domain organization of protein suggests that p48 is an enzyme involved in the tunic tunning and is an important regulator of the organization of the extracellular matrix.

Keywords: ascidian, p48, thrombospondin, tyrosinase, tunic, tunning

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Authors: Michael Brave, Mark Kroll, Steven Karch, Charles Wetli, Michael Graham, Sebastian Kunz, Dorin Panescu

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Background: Conducted electrical weapons (CEW) are now used in 107 countries and are a common law enforcement less-lethal force practice in the United Kingdom (UK), United States of America (USA), Canada, Australia, New Zealand, and others. Use of these devices is rarely temporally associated with the occurrence of sudden arrest-related deaths (ARD). Because such deaths are uncommon, few Medical Examiners (MEs) ever encounter one, and even fewer offices have established comprehensive investigative protocols. Without sufficient scientific data, the role, if any, played by a CEW in a given case is largely supplanted by conjecture often defaulting to a CEW-induced fatal cardiac arrhythmia. In addition to the difficulty in investigating individual deaths, the lack of information also detrimentally affects being able to define and evaluate the ARD cohort generally. More comprehensive, better information leads to better interpretation in individual cases and also to better research. The purpose of this presentation is to provide MEs with a comprehensive evidence-based checklist to assist in the assessment of CEW-ARD cases. Methods: PUBMED and Sociology/Criminology data bases were queried to find all medical, scientific, electrical, modeling, engineering, and sociology/criminology peer-reviewed literature for mentions of CEW or synonymous terms. Each paper was then individually reviewed to identify those that discussed possible bioelectrical mechanisms relating CEW to ARD. A Naranjo-type pharmacovigilance algorithm was also employed, when relevant, to identify and quantify possible direct CEW electrical myocardial stimulation. Additionally, CEW operational manuals and training materials were reviewed to allow incorporation of CEW-specific technical parameters. Results: Total relevant PUBMED citations of CEWs were less than 250, and reports of death extremely rare. Much relevant information was available from Sociology/Criminology data bases. Once the relevant published papers were identified, and reviewed, we compiled an annotated checklist of data that we consider critical to a thorough CEW-involved ARD investigation. Conclusion: We have developed an evidenced-based checklist that can be used by MEs and their staffs to assist them in identifying, collecting, documenting, maintaining, and objectively analyzing the role, if any, played by a CEW in any specific case of sudden death temporally associated with the use of a CEW. Even in cases where the collected information is deemed by the ME as insufficient for formulating an opinion or diagnosis to a reasonable degree of medical certainty, information collected as per the checklist will often be adequate for other stakeholders to use as a basis for informed decisions. Having reviewed the appropriate materials in a significant number of cases careful examination of the heart and brain is likely adequate. Channelopathy testing should be considered in some cases, however it may be considered cost prohibitive (aprox $3000). Law enforcement agencies may want to consider establishing a reserve fund to help manage such rare cases. The expense may stay the enormous costs associated with incident-precipitated litigation.

Keywords: ARD, CEW, police, TASER

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Authors: Nabil Omar, Farah Jibril, Oraib Amjad

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Purpose: Trabecatine is a is a potent marine-derived antineoplastic drug which binds to the minor groove of the DNA, bending DNA towards the major groove resulting in a changed conformation that interferes with several DNA transcription factors, repair pathways and cell proliferation. Trabectedin was approved by the European Medicines Agency (EMA; London, UK) for the treatment of adult patients with advanced stage soft tissue sarcomas in whom treatment with anthracyclines and ifosfamide has failed, or for those who are not candidates for these therapies. The recommended dosing regimen is 1.5 mg/m2 IV over 24 hours every 3 weeks. The purpose of this study was to comprehensively review available data on the safety and efficacy of trabectedin used as indicated for patients at a Tertiary Cancer Center at Qatar. Methods: A medication administration report generated in the electronic health record identified all patients who received trabectedin between November 1, 2015 and November 1, 2017. This retrospective chart review evaluated the indication of trabectedin use, compliance to administration protocol and the recommended monitoring parameters, number of patients improved on the drug and continued treatment, number of patients discontinued treatment due to side-effects and the reported side effects. Progress and discharged notes were utilized to report experienced side effects during trabectedin therapy. A total of 3 patients were reviewed. Results: Total of 2 out of 3 patients who received trabectedin were receiving it for non-FDA and non-EMA, approved indications; metastatic rhabdomyosarcoma and ovarian cancer stage IV with poor prognosis. And only one patient received it as indicated for leiomyosarcoma of left ureter with metastases to liver, lungs and bone. None of the patients has continued the therapy due to development of serious side effects. One patient had stopped the medication after one cycle due to disease progression and transient hepatic toxicity, the other one had disease progression and developed 12 % reduction in LVEF after 12 cycles of trabectedin, and the third patient deceased, had disease progression on trabectedin after the 10th cycle that was received through peripheral line which resulted in developing extravasation and left arm cellulitis requiring debridement. Regarding monitoring parameters, at baseline the three patients had ECHO, and Creatine Phosphokinase (CPK) but it was not monitored during treatment as recommended. Conclusion: Utilizing this medication as indicated with performing the appropriate monitoring parameters as recommended can benefit patients who are receiving it. It is important to reinforce the intravenous administration via central intravenous line, the re-assessment of left ventricular ejection fraction (LVEF) by echocardiogram or multigated acquisition (MUGA) scan at 2- to 3-month intervals thereafter until therapy is discontinued, and CPK and LFTs levels prior to each administration of trabectedin.

Keywords: trabectedin, drug-use evaluation, safety, effectiveness, adverse drug reaction, monitoring

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Authors: Yakup Ulusu, Faruk Ozel, Numan Eczacioglu, Abdurrahman Ozen, Sabriye Acikgoz

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GFP discovered in the mid-1970s, has been used as a marker after replicated genetic study by scientists. In biotechnology, cell, molecular biology, the GFP gene is frequently used as a reporter of expression. In modified forms, it has been used to make biosensors. Many animals have been created that express GFP as an evidence that a gene can be expressed throughout a given organism. Proteins labeled with GFP identified locations are determined. And so, cell connections can be monitored, gene expression can be reported, protein-protein interactions can be observed and signals that create events can be detected. Additionally, monitoring GFP is noninvasive; it can be detected by under UV-light because of simply generating fluorescence. Moreover, GFP is a relatively small and inert molecule, that does not seem to treat any biological processes of interest. The synthesis of GFP has some steps like, to construct the plasmid system, transformation in E. coli, production and purification of protein. GFP carrying plasmid vector pBAD–GFPuv was digested using two different restriction endonuclease enzymes (NheI and Eco RI) and DNA fragment of GFP was gel purified before cloning. The GFP-encoding DNA fragment was ligated into pET28a plasmid using NheI and Eco RI restriction sites. The final plasmid was named pETGFP and DNA sequencing of this plasmid indicated that the hexa histidine-tagged GFP was correctly inserted. Histidine-tagged GFP was expressed in an Escherichia coli BL21 DE3 (pLysE) strain. The strain was transformed with pETGFP plasmid and grown on LuiraBertoni (LB) plates with kanamycin and chloramphenicol selection. E. coli cells were grown up to an optical density (OD 600) of 0.8 and induced by the addition of a final concentration of 1mM isopropyl-thiogalactopyranoside (IPTG) and then grown for additional 4 h. The amino-terminal hexa-histidine-tag facilitated purification of the GFP by using a His Bind affinity chromatography resin (Novagen). Purity of GFP protein was analyzed by a 12 % sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). The concentration of protein was determined by UV absorption at 280 nm (Varian Cary 50 Scan UV/VIS spectrophotometer). Synthesis of GFP-Polymer composite nanofibers was produced by using GFP solution (10mg/mL) and polymer precursor Polyvinylpyrrolidone, (PVP, Mw=1300000) as starting materials and template, respectively. For the fabrication of nanofibers with the different fiber diameter; a sol–gel solution comprising of 0.40, 0.60 and 0.80 g PVP (depending upon the desired fiber diameter) and 100 mg GFP in 10 mL water: ethanol (3:2) mixtures were prepared and then the solution was covered on collecting plate via electro spinning at 10 kV with a feed-rate of 0.25 mL h-1 using Spellman electro spinning system. Results show that GFP-based nano-fiber can be used plenty of biomedical applications such as bio-imaging, bio-mechanic, bio-material and tissue engineering.

Keywords: biomaterial, GFP, nano-fibers, protein expression

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Authors: Eashwar V. Somasundaram, Raoul R. Wadhwa, Jacob G. Scott

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The use of radiomics in measuring geometric properties of tumor images such as size, surface area, and volume has been invaluable in assessing cancer diagnosis, treatment, and prognosis. In addition to analyzing geometric properties, radiomics would benefit from measuring topological properties using persistent homology. Intuitively, features uncovered by persistent homology may correlate to tumor structural features. One example is necrotic cavities (corresponding to 2D topological features), which are markers of very aggressive tumors. We develop a data pipeline in R that clusters tumors images based on persistent homology is used to identify meaningful clinical distinctions between tumors and possibly new relationships not captured by established clinical categorizations. A preliminary analysis was performed on 16 Magnetic Resonance Imaging (MRI) breast tissue segments downloaded from the 'Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis' (I-SPY TRIAL or ISPY1) collection in The Cancer Imaging Archive. Each segment represents a patient’s breast tumor prior to treatment. The ISPY1 dataset also provided the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status data. A persistent homology matrix up to 2-dimensional features was calculated for each of the MRI segmentation. Wasserstein distances were then calculated between all pairwise tumor image persistent homology matrices to create a distance matrix for each feature dimension. Since Wasserstein distances were calculated for 0, 1, and 2-dimensional features, three hierarchal clusters were constructed. The adjusted Rand Index was used to see how well the clusters corresponded to the ER/PR/HER2 status of the tumors. Triple-negative cancers (negative status for all three receptors) significantly clustered together in the 2-dimensional features dendrogram (Adjusted Rand Index of .35, p = .031). It is known that having a triple-negative breast tumor is associated with aggressive tumor growth and poor prognosis when compared to non-triple negative breast tumors. The aggressive tumor growth associated with triple-negative tumors may have a unique structure in an MRI segmentation, which persistent homology is able to identify. This preliminary analysis shows promising results in the use of persistent homology on tumor imaging to assess the severity of breast tumors. The next step is to apply this pipeline to other tumor segment images from The Cancer Imaging Archive at different sites such as the lung, kidney, and brain. In addition, whether other clinical parameters, such as overall survival, tumor stage, and tumor genotype data are captured well in persistent homology clusters will be assessed. If analyzing tumor MRI segments using persistent homology consistently identifies clinical relationships, this could enable clinicians to use persistent homology data as a noninvasive way to inform clinical decision making in oncology.

Keywords: cancer biology, oncology, persistent homology, radiomics, topological data analysis, tumor imaging

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Authors: Paola Millare, Nelinda Catherine Pangilinan

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Background and Aim: Cervical cancer is the most commonly diagnosed gynecological malignancy during pregnancy. Owing to the rarity of the disease, and the complexity of all factors that have to be taken into consideration, standardization of treatment is very difficult. Cervical cancer is the second most common malignancy among women. The treatment of cancer during pregnancy is most challenging in the case of cervical cancer, since the pregnant uterus itself is affected. This report aims to present a case of cervical cancer in a pregnant woman and how to manage this case and several issues accompanied with it. Methods: This is a case of a 28 year-old, Gravida 4 Para 2 (1111), who presented with watery to mucoid, whitish, non-foul smelling and increasing in amount. Internal examination revealed normal external genitalia, parous outlet, cervix was transformed into a fungating mass measuring 5x4 cm, with left parametrial involvement, body of uterus was enlarged to 24 weeks size, no adnexal mass or tenderness. She had cervical punch biopsy, which revealed, adenocarcinoma, well-differentiated cervical tissue. Standard management for cases with stage 2B cervical carcinoma was to start radiation or radical hysterectomy. In the case of patients diagnosed with cervical cancer and currently pregnant, these kind of management will result to fetal loss. The patient still declined the said management and opted to delay the treatment and wait for her baby to reach at least term and proceed to cesarean section as route of delivery. Results: The patient underwent an elective cesarean section at 37th weeks age of gestation, with an outcome of a term, live baby boy APGAR score 7,9 birthweight 2600 grams. One month postpartum, the patient followed up and completed radiotherapy, chemotherapy and brachytherapy. She was advised to go back after 6 months for monitoring. On her last check up, an internal examination was done which revealed normal external genitalia, vagina admits 2 fingers with ease, there is a palpable fungating mass at the cervix measuring 2x2 cm. A repeat gynecologic oncologic ultrasound was done revealing cervical mass, endophytic, grade 1 color score with stromal invasion 35% post radiation reactive lymph nodes with intact paracolpium, pericervical, and parametrial involvement. The patient was then advised to undergo pelvic boost and for close monitoring of the cervical mass. Conclusion: Cervical cancer in pregnancy is rare but is a dilemma for women and their physicians. Treatment should be multidisciplinary and individualized following careful counseling. In this case, the treatment was clearly on the side of preventing the progression of cervical cancer while she is pregnant, however due to ethical reasons, the management deviates on the right of the patient to decide for her own health and her unborn child. The collaborative collection of data relating to treatment and outcome is strongly encouraged.

Keywords: cancer, cervical, ethical, pregnancy

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Authors: Martin Bloomfield

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This paper examines frictions that lie at the heart of any pragmatist conception of religion and moral progress. I take moral progress to require the ability to correctly analyse social problems, provide workable solutions to these problems, and then rationally justify the analyses and solutions used. I take religion here to involve, as a minimal requirement, belief in the existence of God, a god, or gods, such that they are recognisable to most informed observers within the Western tradition. I take pragmatism to belong to, and borrow from, the philosophical traditions of non-absolutism, anti-realism, historicism, and voluntarism. For clarity, the relevant brands of each of these traditions will be examined during the paper. The friction identified in the title may be summed up as follows: those who, like Cornel West (and, when he was alive, Hilary Putnam), are theistic pragmatists with an interest in realising moral progress, have all been aware of a problem inherent in their positions. Assuming it can be argued that religion and moral progress are compatible, a non-absolutist, anti-realist, historicist position nevertheless raises problems that, as Leon Wieseltier pointed out, the pragmatist still believes in a God who isn’t real, and that the truth of any religious statement (including “God exists”) is relative not to any objective reality but to communities of engaged interlocutors; and that, where there are no absolute standards of right and wrong, any analysis of (and solution to) social problems can only be rationally justified relative to one or another community or moral and epistemic framework. Attempts made to universalise these frameworks, notably by Dewey, Gadamer, and Bernstein, through democracy and hermeneutics, fall into either a vicious and infinite regress, or (taking inspiration from Habermas) the problem of moral truths being decided through structures of power. The paper removes this friction by highlighting the work of Christian pragmatist Cornel West through the lens of the philosopher of religion Eleanore Stump. While West recognises that for the pragmatist, the correctness of any propositions about God or moral progress is impossible to rationally justify to any outside the religious, moral or epistemic framework of the speakers themselves without, as he calls it, a ‘locus of truth’ (which is itself free from the difficulties Dewey, Gadamer and Bernstein fall victim to), Stump identifies routes to knowledge which provide such a locus while avoiding the problems of relativism, power dynamics, and regress. She describes “Dominican” and “Franciscan” knowledge (roughly characterised as “propositional” and “non-propositional”), and uses this distinction to identify something Bernstein saw as missing from Gadamer: culture-independent norms, upon which universal agreement can be built. The “Franciscan knowledge” Stump identifies as key is second-personal knowledge of Christ. For West, this allows the knower to access vital culture-independent norms. If correct, instead of the classical view (religion is incompatible with pragmatism), Christianity becomes key to pragmatist knowledge and moral-knowledge claims. Rather than being undermined by pragmatism, Christianity enables pragmatists to make moral and epistemic claims, free from troubling power dynamics and cultural relativism.

Keywords: Cornel West, Cultural Relativism, Gadamer, Philosophy of Religion, Pragmatism

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Authors: M. Fry, L. Fitzpatrick, Julie Considine, R. Z. Shaban, Kate Curtis

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Introduction: The vast majority of older Australians lives independently and are self-managing at home, despite a growing number living with a chronic illness that requires health intervention. Evidence shows that between 50% and 80% of people presenting to the emergency department (ED) are in pain. Australian EDs manage 7.2 million attendances every year and 1.4 million of these are people aged 65 years or more. Research shows that 28% of ED patients aged 65 years or more have Cognitive impairment (CI) associated with dementia, delirium and neurological conditions. Background: Traditional ED service delivery may not be suitable for older people who present with multiple, complex and ongoing illnesses. Likewise, ED clinical staff often perceive that their role should be focused more on immediate and potential lifethreatening illness and conditions which are episodic in nature. Therefore, the needs of older people and their family/carers may not be adequately addressed in the context of an ED presentation. Aim: We aimed to explore the utilisation and characteristics of older people presenting to four metropolitan EDs. Method: The findings being presented are part of a program of research exploring pain management practices for older persons with long bone fractures. The study was conducted across four metropolitan emergency departments of older patients (65years and over) and involved a 12-month randomised medical record audit (n=255). Results: ED presentations across four ED sites in 2012 numbered 168021, with 44778 (26.6%) patients aged 65 and over. Of the 44778 patients, the average age was 79.1 years (SD 8.54). There were more females 23932 (53.5%). The majority (26925: 85.0%) of older persons self-referred to the ED and lived independently. The majority arrived by ambulance (n=18553: 41.4%) and were allocated triage category was 3 (n=19,507:43.65%) or Triage category 4 at (n=15,389: 34.43%). The top five triage symptom presentations involved pain (n=8088; 18.25%), dyspnoea (n=4735; 10.7%), falls (n=4032; 9.1%), other (n=3984; 9.0%), cardiac (n=2987; 6.7%). The top five system based diagnostic presentations involved musculoskeletal (n=8902; 20.1%), cardiac (n=6704:15.0%), respiratory (n=4933; 11.0%), neurological (n=4909; 11.0%), gastroenterology (n=4321; 9.7%). On review of one tertiary hospital database the vital signs on average at time triage: Systolic Blood Pressure 143.6mmHg. Heart Rate 83.4 beats/minute; Respiratory Rate 18.5 breaths/ minute; Oxygen saturation 97.0% and Tympanic temperature 36.7 and Blood Glucose Level 7.4mmols/litre. The majority presented with a Glasgow Coma Score of 14 or higher. On average the older person stayed in the ED 4:56 (SD 3:28minutes).The average time to be seen was 39 minutes (SD 48 minutes). The majority of older persons were admitted (n=27562: 61.5%), did not wait for treatment (n= 8879: 0.02%) discharged home (n=16256: 36.0%). Conclusion: The vast majority of older persons are living independently, although many require admission on arrival to the ED. Many arrived in pain and with musculoskeletal injuries and or conditions. New models of care need to be considered, which may better support self-management and independent living of the older person and the National Emergency Access Targets.

Keywords: chronic, older person, aged care, emergency department

Procedia PDF Downloads 236

Authors: Beverly Wang

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Background: Rosai-Dorfman disease (RDD), aka sinus histiocytosis with massive lymphadenopathy, is a rare, idiopathic histiocytic proliferative disorder. Although RDD can be seen involving the head and neck lymph nodes, rarely it can affect other extranodal sites. It present 3 unique cases of RDD affecting the nasal cavity, paranasal sinuses, and ear canal. The initial clinical presentation on two cases mimicked a malignant neoplasm. The 3rd case of RDD co-existed with a cholesteatoma of the ear canal. The clinical presentation, histology and immunohistochemical stains, and radiographic findings are discussed. Design: An overview of 3 cases of RDD affected sinonasal cavity and ear canal from UCI Medical Center was conducted. Case 1: A 61 year old male complaining of breathing difficulty presented with bilateral polypoid sinonasal masses and severe nasal obstruction. The masses elevated the nasal floor, and involved the anterior nasal septum to lateral wall. It was endoscopically excised. At intraoperative consultation, frozen section reported a pleomorphic spindle cell neoplasm with scattered large atypical spindle cells, resembling a high grade sarcoma. Case 2: A 46 year old male presented with recurrent bilateral maxillary chronic sinusitis with mass formation, clinically suspicious for malignant lymphoma. Excisional tissue sample showed large irregular spindled histiocytes with abundant granular and vacuolated cytoplasm. Case 3: A 36 year old female with a history of asthma initially presented with left-sided chronic otalgia, occasional nausea, vertigo, and fluctuating pain exacerbated by head movement and temperature changes. CT scan revealed an external auditory canal mass extending to the middle ear, coexisting with a small cholesteatoma. Results: The morphology of all cases revealed large atypical spindled histiocytes resembling fibrohistiocytic or myofibroblastic proliferative neoplasms. Scattered emperipolesis was seen. All 3 cases were confirmed as extranodal sinus RDD, confirmed by immunohistochemistry. The large atypical cells were positive for S100, CD68, and CD163. No evidence for malignancy was identified. Case 3 showed concurrent RDD co-existing with a cholesteatoma. Conclusion: Due to its rarity and variable clinical presentations, the diagnosis of RDD is seldom clinically considered. Extranodal sinus RDD morphologically can be pitfall as mimicker of spindly neoplasm, especially at intraoperative consultation. It can create diagnostic and therapeutic challenges. Correlation of radiological findings with histologic features will help to reach the diagnosis.

Keywords: head and neck, extranodal, rosai-dorfman disease, mimicker, immunohistochemistry

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Authors: S. Delgado, C. Cerrada, R. S. Gómez

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This research introduces an approach to voxelizing the surfaces of triangular meshes with efficiency and accuracy. Our method leverages parallel equidistant scan-lines and introduces a Gap Detection technique to address the limitations of existing approaches. We present a comprehensive study showcasing the method's effectiveness, scalability, and versatility in different scenarios. Voxelization is a fundamental process in computer graphics and simulations, playing a pivotal role in applications ranging from scientific visualization to virtual reality. Our algorithm focuses on enhancing the voxelization process, especially for complex models and high resolutions. One of the major challenges in voxelization in the Graphics Processing Unit (GPU) is the high cost of discovering the same voxels multiple times. These repeated voxels incur in costly memory operations with no useful information. Our scan-line-based method ensures that each voxel is detected exactly once when processing the triangle, enhancing performance without compromising the quality of the voxelization. The heart of our approach lies in the use of parallel, equidistant scan-lines to traverse the interiors of triangles. This minimizes redundant memory operations and avoids revisiting the same voxels, resulting in a significant performance boost. Moreover, our method's computational efficiency is complemented by its simplicity and portability. Written as a single compute shader in Graphics Library Shader Language (GLSL), it is highly adaptable to various rendering pipelines and hardware configurations. To validate our method, we conducted extensive experiments on a diverse set of models from the Stanford repository. Our results demonstrate not only the algorithm's efficiency, but also its ability to produce 26 tunnel free accurate voxelizations. The Gap Detection technique successfully identifies and addresses gaps, ensuring consistent and visually pleasing voxelized surfaces. Furthermore, we introduce the Slope Consistency Value metric, quantifying the alignment of each triangle with its primary axis. This metric provides insights into the impact of triangle orientation on scan-line based voxelization methods. It also aids in understanding how the Gap Detection technique effectively improves results by targeting specific areas where simple scan-line-based methods might fail. Our research contributes to the field of voxelization by offering a robust and efficient approach that overcomes the limitations of existing methods. The Gap Detection technique fills a critical gap in the voxelization process. By addressing these gaps, our algorithm enhances the visual quality and accuracy of voxelized models, making it valuable for a wide range of applications. In conclusion, "Closing the Gap: Efficient Voxelization with Equidistant Scan-lines and Gap Detection" presents an effective solution to the challenges of voxelization. Our research combines computational efficiency, accuracy, and innovative techniques to elevate the quality of voxelized surfaces. With its adaptable nature and valuable innovations, this technique could have a positive influence on computer graphics and visualization.

Keywords: voxelization, GPU acceleration, computer graphics, compute shaders

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Authors: Iordana Neamtu, Aurica P. Chiriac, Loredana E. Nita, Mihai Asandulesa, Elena Butnaru, Nita Tudorachi, Alina Diaconu

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In the last decade, the attention of many researchers is focused on the synthesis of innovative “intelligent” copolymer structures with great potential for different uses. This considerable scientific interest is stimulated by possibility of the significant improvements in physical, mechanical, thermal and other important specific properties of these materials. Functionalization of polymer in synthesis by designing a suitable composition with the desired properties and applications is recognized as a valuable tool. In this work is presented a comparative study of the properties of the new copolymers poly(maleic anhydride maleic-co-3,9-divinyl-2,4,8,10-tetraoxaspiro[5.5]undecane) and poly(itaconic-anhydride-co-3,9-divinyl-2,4,8,10-tetraoxaspiro[5.5]undecane) obtained by radical polymerization in dioxane, using 2,2′-azobis(2-methylpropionitrile) as free-radical initiator. The comonomers are able for generating special effects as for example network formation, biodegradability and biocompatibility, gel formation capacity, binding properties, amphiphilicity, good oxidative and thermal stability, good film formers, and temperature and pH sensitivity. Maleic anhydride (MA) and also the isostructural analog itaconic anhydride (ITA) as polyfunctional monomers are widely used in the synthesis of reactive macromolecules with linear, hyperbranched and self & assembled structures to prepare high performance engineering, bioengineering and nano engineering materials. The incorporation of spiroacetal groups in polymer structures improves the solubility and the adhesive properties, induce good oxidative and thermal stability, are formers of good fiber or films with good flexibility and tensile strength. Also, the spiroacetal rings induce interactions on ether oxygen such as hydrogen bonds or coordinate bonds with other functional groups determining bulkiness and stiffness. The synthesized copolymers are analyzed by DSC, oscillatory and rotational rheological measurements and dielectric spectroscopy with the aim of underlying the heating behavior, solution viscosity as a function of shear rate and temperature and to investigate the relaxation processes and the motion of functional groups present in side chain around the main chain or bonds of the side chain. Acknowledgments This work was financially supported by the grant of the Romanian National Authority for Scientific Research, CNCS-UEFISCDI, project number PN-II-132/2014 “Magnetic biomimetic supports as alternative strategy for bone tissue engineering and repair’’ (MAGBIOTISS).

Keywords: Poly(maleic anhydride-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5)undecane); Poly(itaconic anhydride-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5)undecane); DSC; oscillatory and rotational rheological analysis; dielectric spectroscopy

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Authors: Pinar Erturk, Sevde Altuntas, Fatih Buyukserin

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In order to obtain an effective integration between an implant and a bone, implant surfaces should have similar properties to bone tissue surfaces. Especially mimicry of the chemical, mechanical and topographic properties of the implant to the bone is crucial for fast and effective osseointegration. Titanium-based biomaterials are more preferred in clinical use, and there are studies of coating these implants with oxide layers that have chemical/nanotopographic properties stimulating cell interactions for enhanced osseointegration. There are low success rates of current implantations, especially in craniofacial implant applications, which are large and vital zones, and the oxide layer coating increases bone-implant integration providing long-lasting implants without requiring revision surgery. Our aim in this study is to examine bone-cell behavior on titanium implants with an aluminum oxide layer (AAO) on effective osseointegration potential in the deformation of large zones with difficult spontaneous healing. In our study, aluminum layer coated titanium surfaces were anodized in sulfuric, phosphoric, and oxalic acid, which are the most common used AAO anodization electrolytes. After morphologic, chemical, and mechanical tests on AAO coated Ti substrates, viability, adhesion, and mineralization of adult bone cells on these substrates were analyzed. Besides with atomic layer deposition (ALD) as a sensitive and conformal technique, these surfaces were coated with pure alumina (5 nm); thus, cell studies were performed on ALD-coated nanoporous oxide layers with suppressed ionic content too. Lastly, in order to investigate the effect of the topography on the cell behavior, flat non-porous alumina layers on silicon wafers formed by ALD were compared with the porous ones. Cell viability ratio was similar between anodized surfaces, but pure alumina coated titanium and anodized surfaces showed a higher viability ratio compared to bare titanium and bare anodized ones. Alumina coated titanium surfaces, which anodized in phosphoric acid, showed significantly different mineralization ratios after 21 days over other bare titanium and titanium surfaces which anodized in other electrolytes. Bare titanium was the second surface that had the highest mineralization ratio. Otherwise, titanium, which is anodized in oxalic acid electrolyte, demonstrated the lowest mineralization. No significant difference was shown between bare titanium and anodized surfaces except AAO titanium surface anodized in phosphoric acid. Currently, osteogenic activities of these cells on the genetic level are investigated by quantitative real-time polymerase chain reaction (qRT-PCR) analysis results of RUNX-2, VEGF, OPG, and osteopontin genes. Also, as a result of the activities of the genes mentioned before, Western Blot will be used for protein detection. Acknowledgment: The project is supported by The Scientific and Technological Research Council of Turkey.

Keywords: alumina, craniofacial implant, MG-63 cell line, osseointegration, oxalic acid, phosphoric acid, sulphuric acid, titanium

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Authors: Ting-I Lin

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Objective: This article explores the nursing care experience of a 51-year-old terminal lung cancer patient admitted to the intensive care unit (ICU) following an upper right lobectomy. The patient initially sought emergency treatment due to worsening cough and dyspnea, which led to the placement of an endotracheal tube following sudden deterioration. Subsequent CT scans and chest X-rays revealed a tumor in the upper right lung with metastases to the lungs, liver, bones, and adrenal glands. The patient underwent a right upper lobectomy and a wedge resection of the right middle lobe. Pathology staging: T4N3M1c and the patient was diagnosed with advanced cancer postoperatively. Method: During the care period, nursing staff continuously monitored the patient’s physiological data through observations, direct care, interviews, physical assessments, and review of the patient’s medical records. The nursing team collaborated with the critical care team and the palliative care team, using Gordon's Eleven Functional Health Patterns to conduct a comprehensive assessment. The key health problems identified included pain related to postoperative cancer resection and invasive devices, fear of death due to rapid disease progression, and altered tissue perfusion associated with hemodynamic instability. Results: Postoperatively, the patient experienced pain from the surgical wound and dyspnea due to extensive metastasis, often leading to confusion. Through the adjustment of pain medication, the patient’s discomfort was alleviated, using Morphine 8 mg in 0.9% normal saline 60 ml IV drip q6h prn, and Ultracet 37.5 mg/325 mg 1# PO q6h. Additionally, lavender essential oil inhalation and limb massage were provided for 15 minutes four times a day. The patient’s FLACC pain score decreased from 7 to below 3. After respiratory training, the endotracheal tube was successfully removed, and the patient was weaned off the ventilator. Triflow exercises were used to promote alveolar expansion, with the goal of achieving 2 balls for 10 seconds, 5 repetitions per session, 6-8 times a day. The patient’s breathing stabilized at 16-18 breaths per minute, body temperature remained between 35.8°C and 36.1°C, and the mean arterial pressure was maintained between 60-80 mmHg. Conclusion: The critical care team and the palliative care team held a family meeting to discuss not only the patient’s care but also the emotional well-being of the family. Visiting hours were increased to two times per day, one hour each time, allowing the patient and family to express love and gratitude, which strengthened their emotional connection and reduced the patient’s anxiety from severe to mild. The family expressed that they had no regrets. After the patient was transferred to the general ward, the nursing team continued to provide end-of-life care with genuine empathy, compassion, and religious support, helping both the patient and family through the final stage of life.

Keywords: multiple metastases, lung cancer, palliative care, nursing experience

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Authors: Mustafa M. Donma, Orkide Donma

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Obesity is a low-grade inflammatory state. Childhood obesity is a multisystem disease, which is associated with a number of complications as well as potentially negative consequences. Gender is an important universal risk factor for many diseases. Hematological indices differ significantly by gender. This should be considered during the evaluation of obese children. The aim of this study is to detect hematologic indices that differ by gender in morbid obese (MO) children. A total of 134 MO children took part in this study. The parents filled an informed consent form and the approval from the Ethics Committee of Namik Kemal University was obtained. Subjects were divided into two groups based on their genders (64 females aged 10.2±3.1 years and 70 males aged 9.8±2.2 years; p ≥ 0.05). Waist-to-hip as well as head-to-neck ratios and body mass index (BMI) values were calculated. The children, whose WHO BMI-for age and sex percentile values were > 99 percentile, were defined as MO. Hematological parameters [haemoglobin, hematocrit, erythrocyte count, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, red blood cell distribution width, leukocyte count, neutrophil %, lymphocyte %, monocyte %, eosinophil %, basophil %, platelet count, platelet distribution width, mean platelet volume] were determined by the automatic hematology analyzer. SPSS was used for statistical analyses. P ≤ 0.05 was the degree for statistical significance. The groups included children having mean±SD value of BMI as 26.9±3.4 kg/m² for males and 27.7±4.4 kg/m² for females (p ≥ 0.05). There was no significant difference between ages of females and males (p ≥ 0.05). Males had significantly increased waist-to-hip ratios (0.95±0.08 vs 0.91±0.08; p=0.005) and mean corpuscular hemoglobin concentration values (33.6±0.92 vs 33.1±0.83; p=0.001) compared to those of females. Significantly elevated neutrophil (4.69±1.59 vs 4.02±1.42; p=0.011) and neutrophil-to-lymphocyte ratios (1.70±0.71 vs 1.39±0.48; p=0.004) were detected in females. There was no statistically significant difference between groups in terms of C-reactive protein values (p ≥ 0.05). Adipose tissue plays important roles during the development of obesity and associated diseases such as metabolic syndrom and cardiovascular diseases (CVDs). These diseases may cause changes in complete blood cell count parameters. These alterations are even more important during childhood. Significant gender effects on the changes of neutrophils, one of the white blood cell subsets, were observed. The findings of the study demonstrate the importance of considering gender in clinical studies. The males and females may have distinct leukocyte-trafficking profiles in inflammation. Female children had more circulating neutrophils, which may be the indicator of an increased risk of CVDs, than male children within this age range during the late stage of obesity. In recent years, females represent about half of deaths from CVDs; therefore, our findings may be the indicator of the increasing tendency of this risk in females starting from childhood.

Keywords: children, gender, morbid obesity, neutrophil-to-lymphocyte ratio

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Authors: Michael Josef Schwerer, Oliver Peschel

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Background: The sense and purpose of forensic postmortem examinations are undoubtedly the same in Institutes of Legal Medicine all over the world. Cause and manner of death must be determined, persons responsible for unnatural death must be brought to justice, and accidents demand changes in the respective scenarios to avoid future mishaps. The latter particularly concerns aircraft accidents, not only regarding consequences from criminal or civil law but also in pursuance of the International Civil Aviation Authority’s regulations, which demand lessons from mishap investigations to improve flight safety. Irrespective of the distinct circumstances of a given casualty or the respective questions in subsequent death investigations, a forensic autopsy is the basis for all further casework, the clue to otherwise hidden solutions, and the crucial limitation for final success when not all possible findings have been properly collected. This also implies that the targeted work of police forces and expert witnesses strongly depends on the quality of forensic pathology practice. Deadly events in foreign countries, which lead to investigations not only abroad but also in Germany, can be challenging in this context. Frequently, second-look autopsies after the repatriation of the deceased to Germany are requested by the legal authorities to ensure proper and profound documentation of all relevant findings. Aims and Methods: To validate forensic postmortem practice abroad, a retrospective study using the findings in the corresponding second-look autopsies in the Institute of Legal Medicine Munich over the last 20 years was carried out. New findings unreported in the previous autopsy were recorded and judged for their relevance to solving the respective case. Further, the condition of the corpse at the time of the second autopsy was rated to discuss artifacts mimicking evidence or the possibility of lost findings resulting from, e.g., decomposition. Recommendations for future handling of death cases abroad and efficient autopsy practice were pursued. Results and Discussion: Our re-evaluation confirmed a high quality of autopsy practice abroad in the vast majority of cases. However, in some casework, incomplete documentation of pathology findings was revealed along with either insufficient or misconducted dissection of organs. Further, some of the bodies showed missing parts of some organs, most probably resulting from sampling for histology studies during the first postmortem. For the aeromedical evaluation of a decedent’s health status prior to an aviation mishap, particularly lost or obscured findings in the heart, lungs, and brain impeded expert testimony. Moreover, incomplete fixation of the body or body parts for repatriation was seen in several cases. This particularly involved previously dissected organs deposited back into the body cavities at the end of the first autopsy. Conclusions and Recommendations: Detailed preparation in the first forensic autopsy avoids the necessity of a second-look postmortem in the majority of cases. To limit decomposition changes during repatriation from abroad, special care must be taken to include pre-dissected organs in the chemical fixation process, particularly when they are separated from the blood vessels and just deposited back into the body cavities.

Keywords: autopsy practice, second-look autopsy, retrospective study, quality standards, decomposition changes, repatriation

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Authors: Yazan S. Khaled, Shazana Shamsuddin, Jim Tiernan, Mike McPherson, Thomas Hughes, Paul Millner, David G. Jayne

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Introduction: There is a need for real-time imaging of colorectal cancer (CRC) to allow tailored surgery to the disease stage. Fluorescence guided laparoscopic imaging of primary colorectal cancer and the draining lymphatics would potentially bring stratified surgery into clinical practice and realign future CRC management to the needs of patients. Fluorescent nanoparticles can offer many advantages in terms of intra-operative imaging and therapy (theranostic) in comparison with traditional soluble reagents. Nanoparticles can be functionalised with diverse reagents and then targeted to the correct tissue using an antibody or Affimer (artificial binding protein). We aimed to develop and test fluorescent silica nanoparticles and targeted against CRC using an anti-carcinoembryonic antigen (CEA) Affimer (Aff). Methods: Anti-CEA and control Myoglobin Affimer binders were subcloned into the expressing vector pET11 followed by transformation into BL21 Star™ (DE3) E.coli. The expression of Affimer binders was induced using 0.1 mM isopropyl β-D-1-thiogalactopyranoside (IPTG). Cells were harvested, lysed and purified using nickle chelating affinity chromatography. The photosensitiser Foslip (soluble analogue of 5,10,15,20-Tetra(m-hydroxyphenyl) chlorin) was incorporated into the core of silica nanoparticles using water-in-oil microemulsion technique. Anti-CEA or control Affs were conjugated to silica nanoparticles surface using sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo SMCC) chemical linker. Binding of CEA-Aff or control nanoparticles to colorectal cancer cells (LoVo, LS174T and HC116) was quantified in vitro using confocal microscopy. Results: The molecular weights of the obtained band of Affimers were ~12.5KDa while the diameter of functionalised silica nanoparticles was ~80nm. CEA-Affimer targeted nanoparticles demonstrated 9.4, 5.8 and 2.5 fold greater fluorescence than control in, LoVo, LS174T and HCT116 cells respectively (p < 0.002) for the single slice analysis. A similar pattern of successful CEA-targeted fluorescence was observed in the maximum image projection analysis, with CEA-targeted nanoparticles demonstrating 4.1, 2.9 and 2.4 fold greater fluorescence than control particles in LoVo, LS174T, and HCT116 cells respectively (p < 0.0002). There was no significant difference in fluorescence for CEA-Affimer vs. CEA-Antibody targeted nanoparticles. Conclusion: We are the first to demonstrate that Foslip-doped silica nanoparticles conjugated to anti-CEA Affimers via SMCC allowed tumour cell-specific fluorescent targeting in vitro, and had shown sufficient promise to justify testing in an animal model of colorectal cancer. CEA-Affimer appears to be a suitable targeting molecule to replace CEA-Antibody. Targeted silica nanoparticles loaded with Foslip photosensitiser is now being optimised to drive photodynamic killing, via reactive oxygen generation.

Keywords: colorectal cancer, silica nanoparticles, Affimers, antibodies, imaging

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Authors: O. Gsib, U. Peirera, C. Egles, S. A. Bencherif

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In skin regenerative medicine, one of the critical issues is to produce a three-dimensional scaffold with optimized porosity for dermal fibroblast infiltration and neovascularization, which exhibits high mechanical properties and displays sufficient wound healing characteristics. In this study, we report on the synthesis and characterization of macroporous sequential interpenetrating polymer networks (IPNs) combining skin wound healing properties of fibrin with the excellent physical properties of polyethylene glycol (PEG). Fibrin fibers serve as a provisional biologically active network to promote cell adhesion and proliferation while PEG provides the mechanical stability to maintain the entire 3D construct. After having modified both PEG and Serum Albumin (used for promoting enzymatic degradability) by adding methacrylate residues (PEGDM and SAM, respectively), Fibrin/PEGDM-SAM sequential IPNs were synthesized as follows: Macroporous sponges were first produced from PEGDM-SAM hydrogels by a freeze-drying technique and then rehydrated by adding the fibrin precursors. Environmental Scanning Electron Microscopy (ESEM) and Confocal Laser Scanning Microscopy (CLSM) were used to characterize their microstructure. Human dermal fibroblasts were cultivated during one week in the constructs and different cell culture parameters (viability, morphology, proliferation) were evaluated. Subcutaneous implantations of the scaffolds were conducted on five-week old male nude mice to investigate their biocompatibility in vivo. We successfully synthesized interconnected and macroporous Fibrin/PEGDM-SAM sequential IPNs. The viability of primary dermal fibroblasts was well maintained (above 90%) after 2 days of culture. Cells were able to adhere, spread and proliferate in the scaffolds suggesting the suitable porosity and intrinsic biologic properties of the constructs. The fibrin network adopted a spider web shape that covered partially the pores allowing easier cell infiltration into the macroporous structure. To further characterize the in vitro cell behavior, cell proliferation (EdU incorporation, MTS assay) is being studied. Preliminary histological analysis of animal studies indicated the persistence of hydrogels even after one-month post implantation and confirmed the absence of inflammation response, good biocompatibility and biointegration of our scaffolds within the surrounding tissues. These results suggest that our Fibrin/PEGDM-SAM IPNs could be considered as potential candidates for dermis regenerative medicine. Histological analysis will be completed to further assess scaffold remodeling including de novo extracellular matrix protein synthesis and early stage angiogenesis analysis. Compression measurements will be conducted to investigate the mechanical properties.

Keywords: fibrin, hydrogels for dermal reconstruction, polyethylene glycol, semi-interpenetrating polymer network

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Authors: Elena Filova, Ondrej Kaplan, Marie Markova, Helena Dragounova, Roman Matejka, Eduard Brynda, Lucie Bacakova

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Decellularized vessels have been evaluated as small-diameter vascular prostheses. Reseeding autologous cells onto decellularized tissue prior implantation should prolong prostheses function and make them living tissues. Suitable cell types for reseeding are both endothelial cells and bone marrow-derived stem cells, with a capacity for differentiation into smooth muscle cells upon mechanical loading. Endothelial cells assure antithrombogenicity of the vessels and MSCs produce growth factors and, after their differentiation into smooth muscle cells, they are contractile and produce extracellular matrix proteins as well. Fibrin is a natural scaffold, which allows direct cell adhesion based on integrin receptors. It can be prepared autologous. Fibrin can be modified with bound growth factors, such as basic fibroblast growth factor (FGF-2) and vascular endothelial growth factor (VEGF). These modifications in turn make the scaffold more attractive for cells ingrowth into the biological scaffold. The aim of the study was to prepare thin surface-attached fibrin assemblies with bound FGF-2 and VEGF, and to evaluate growth and differentiation of bone marrow-derived mesenchymal stem cells on the fibrin (Fb) assemblies. Following thin surface-attached fibrin assemblies were prepared: Fb, Fb+VEGF, Fb+FGF2, Fb+heparin, Fb+heparin+VEGF, Fb+heparin+FGF2, Fb+heparin+FGF2+VEGF. Cell culture poly-styrene and glass coverslips were used as controls. Human MSCs (passage 3) were seeded at the density of 8800 cells/1.5 mL alpha-MEM medium with 2.5% FS and 200 U/mL aprotinin per well of a 24-well cell culture. The cells have been cultured on the samples for 6 days. Cell densities on day 1, 3, and 6 were analyzed after staining with LIVE/DEAD cytotoxicity/viability assay kit. The differentiation of MSCs is being analyzed using qPCR. On day 1, the highest density of MSCs was observed on Fb+VEGF and Fb+FGF2. On days 3 and 6, there were similar densities on all samples. On day 1, cell morphology was polygonal and spread on all sample. On day 3 and 6, MSCs growing on Fb assemblies with FGF2 became apparently elongated. The evaluation of expression of genes for von Willebrand factor and CD31 (endothelial cells), for alpha-actin (smooth muscle cells), and for alkaline phosphatase (osteoblasts) is in progress. We prepared fibrin assemblies with bound VEGF and FGF-2 that supported attachment and growth of mesenchymal stem cells. The layers are promising for improving the ingrowth of MSCs into the biological scaffold. Supported by the Technology Agency of the Czech Republic TA04011345, and Ministry of Health NT11270-4/2010, and BIOCEV – Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University” project (CZ.1.05/1.1.00/02.0109), funded by the European Regional Development Fund for their financial supports.

Keywords: fibrin assemblies, FGF-2, mesenchymal stem cells, VEGF

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Authors: Mohammed Makki, Milad Showkatbakhsh, Aiman Tabony

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Computational applications of natural evolutionary processes as problem-solving tools have been well established since the mid-20th century. However, their application within architecture and design has only gained ground in recent years, with an increasing number of academics and professionals in the field electing to utilize evolutionary computation to address problems comprised from multiple conflicting objectives with no clear optimal solution. Recent advances in computer science and its consequent constructive influence on the architectural discourse has led to the emergence of multiple algorithmic processes capable of simulating the evolutionary process in nature within an efficient timescale. Many of the developed processes of generating a population of candidate solutions to a design problem through an evolutionary based stochastic search process are often driven through the application of both environmental and architectural parameters. These methods allow for conflicting objectives to be simultaneously, independently, and objectively optimized. This is an essential approach in design problems with a final product that must address the demand of a multitude of individuals with various requirements. However, one of the main challenges encountered through the application of an evolutionary process as a design tool is the ability for the simulation to maintain variation amongst design solutions in the population while simultaneously increasing in fitness. This is most commonly known as the ‘golden rule’ of balancing exploration and exploitation over time; the difficulty of achieving this balance in the simulation is due to the tendency of either variation or optimization being favored as the simulation progresses. In such cases, the generated population of candidate solutions has either optimized very early in the simulation, or has continued to maintain high levels of variation to which an optimal set could not be discerned; thus, providing the user with a solution set that has not evolved efficiently to the objectives outlined in the problem at hand. As such, the experiments presented in this paper seek to achieve the ‘golden rule’ by incorporating a mathematical fitness criterion for the development of an urban tissue comprised from the superblock as its primary architectural element. The mathematical value investigated in the experiments is the standard deviation factor. Traditionally, the standard deviation factor has been used as an analytical value rather than a generative one, conventionally used to measure the distribution of variation within a population by calculating the degree by which the majority of the population deviates from the mean. A higher standard deviation value delineates a higher number of the population is clustered around the mean and thus limited variation within the population, while a lower standard deviation value is due to greater variation within the population and a lack of convergence towards an optimal solution. The results presented will aim to clarify the extent to which the utilization of the standard deviation factor as a fitness criterion can be advantageous to generating fitter individuals in a more efficient timeframe when compared to conventional simulations that only incorporate architectural and environmental parameters.

Keywords: architecture, computation, evolution, standard deviation, urban

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Authors: Dina Farran, Mark Ashworth, Fiona Gaughran

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Atrial fibrillation (AF), the most prevalent cardiac arrhythmia, is associated with an increased risk of stroke, contributing to heart failure and death. In this project, we aim to improve patient safety by screening for stroke risk among people with AF and co-morbid mental illness. To do so, we started by conducting a systematic review and meta-analysis on prevalence, management, and outcomes of AF in people with Serious Mental Illness (SMI) versus the general population. We then evaluated oral anticoagulation (OAC) prescription trends in people with AF and co-morbid SMI in King’s College Hospital. We also evaluated the association between mental illness severity and OAC prescription in eligible patients in South London and Maudsley (SLaM) NHS Foundation Trust. Next, we implemented an electronic clinical decision support system (eCDSS) consisting of a visual prompt on patient electronic Personal Health Records to screen for AF-related stroke risk in three Mental Health of Older Adults wards at SLaM. Finally, we assessed the feasibility and acceptability of the eCDSS by qualitatively investigating clinicians’ perspectives of the potential usefulness of the eCDSS (pre-intervention) and their experiences and their views regarding its impact on clinicians and patients (post-intervention). The systematic review showed that people with SMI had low reported rates of AF. AF patients with SMI were less likely to receive OAC than the general population. When receiving warfarin, people with SMI, particularly bipolar disorder, experienced poor anticoagulation control compared to the general population. Meta-analysis showed that SMI was not significantly associated with an increased risk of stroke or major bleeding when adjusting for underlying risk factors. The main findings of the first observational study were that among AF patients having a high stroke risk, those with co-morbid SMI were less likely than non-SMI to be prescribed any OAC, particularly warfarin. After 2019, there was no significant difference between the two groups. In the second observational study, patients with AF and co-morbid SMI were less likely to be prescribed any OAC compared to those with dementia, substance use disorders, or common mental disorders, adjusting for age, sex, stroke, and bleeding risk scores. Among AF patients with co-morbid SMI, warfarin was less likely to be prescribed to those having alcohol or substance dependency, serious self-injury, hallucinations or delusions, and activities of daily living impairment. In the intervention, clinicians were asked to confirm the presence of AF, clinically assess stroke and bleeding risks, record risk scores in clinical notes, and refer patients at high risk of stroke to OAC clinics. Clinicians reported many potential benefits for the eCDSS, including improving clinical effectiveness, better identification of patients at risk, safer and more comprehensive care, consistency in decision making and saving time. Identified potential risks included rigidity in decision-making, overreliance, reduced critical thinking, false positive recommendations, annoyance, and increased workload. This study presents a unique opportunity to quantify AF patients with mental illness who are at high risk of severe outcomes using electronic health records. This has the potential to improve health outcomes and, therefore patients' quality of life.

Keywords: atrial fibrillation, stroke, mental health conditions, electronic clinical decision support systems

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