Search results for: topical ontology

Authors: Boudjelal Amel

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Arisarum vulgare, a member of the Araceae family, is an herbaceous perennial widely distributed in the Mediterranean region. A. vulgare is recognized for its medicinal properties and holds significant traditional importance in Algeria for the treatment of various human ailments, including pain, infections, inflammation, digestive disorders, skin problems, eczema, cancer, wounds, burns and gynecological diseases. Despite its extensive traditional use, scientific exploration of A. vulgare remains limited. The study aims to investigate for the first time the therapeutic potential of A. vulgare ethanolic extract obtained by ultrasound-assisted extraction. The chemical composition of the extract was determined by LC-MS/MS analysis. For in vitro phytopharmacological evaluation, several assays, including DPPH, ABTS, FRAP and reducing power, were employed to evaluate the antioxidant activity. The antibacterial activity was assessed againt Escherichia coli, Salmonella typhimurium, Staphylococus aureus, Enterococcus feacium by disk diffusion and microdilution methods. The possible inhibitory activity of ethanolic extract was analyzed against the cholinesterases enzymes (AChE and BChE). The DNA protection activity of A. vulgare ethanolic extract was estimated using the agarose gel electrophoresis method. The capacities of the extract to protect plasmid DNA (pBR322) from the oxidizing effects of H2O2 and UV treatment were evaluated by their DNA-breaking forms. The in vivo wound healing potential of a traditional ointment containing 5% of A. vulgare ethanolic extract was also investigated. The LC-MS/MS profiling of the extract revealed the presence of various bioactive compounds, including naringenin, chlorogenic, vanillic, cafeic, coumaric acids, trans-cinnamic and trans ferrulic acids. The plant extract presented considerable antioxidant potential, being the most active for Reducing power (0,07326±0.001 mg/ml) and DPPH (0.14±0.004 mg/ml). The extract showed the highest inhibition zone diameter against Enterococcus feacium (36±0.1 mm). The ethanolic extract of A. vulgare suppressed the growth of Staphylococus aureus, Escherichia coli and Salmonella typhimurium according to the MIC values. The extract of the plant significantly inhibited both AChE and BChE enzymes. DNA protection activity of the A. vulgare extract was determined as 90.41% for form I and 51.92% for form II. The in vivo experiments showed that 5% ethanolic extract ointment accelerated the wound healing process. The topical application of the traditional formulation enhanced wound closure (95,36±0,6 %) and improved histological parameters in the treated group compared to the control groups. The promising biological properties of Arisarum vulgare revealed that the plant could be appraised as a potential origin of bioactive molecules having multifunctional medicinal uses.

Keywords: arisarum vulgare, LC-MS/MS, antioxidant activity, antimicrobial activity, cholinesterases enzymes inhibition, dna-damage activity, in vivo wound healing

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Authors: A. Volperts, G. Dobele, A. Zhurinsh, I. Kruusenberg, A. Plavniece, J. Locs

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Nowadays energy consumption constantly increases and development of effective and cheap electrochemical sources of power, such as fuel cells and electrochemical capacitors, is topical. Due to their high specific power, charge and discharge rates, working lifetime supercapacitor based energy accumulation systems are more and more extensively being used in mobile and stationary devices. Lignocellulosic materials are widely used as precursors and account for around 45% of the total raw materials used for the manufacture of activated carbon which is the most suitable material for supercapacitors. First part of our research is devoted to study of influence of main stages of wood thermochemical activation parameters on activated carbons porous structure formation. It was found that the main factors governing the properties of carbon materials are specific surface area, volume and pore size distribution, particles dispersity, ash content and oxygen containing groups content. Influence of activated carbons attributes on capacitance and working properties of supercapacitor are demonstrated. The correlation between activated carbons porous structure indices and electrochemical specifications of supercapacitors with electrodes made from these materials has been determined. It is shown that if synthesized activated carbons are used in supercapacitors then high specific capacitances can be reached – more than 380 F/g in 4.9M sulfuric acid based electrolytes and more than 170 F/g in 1 M tetraethylammonium tetrafluoroborate in acetonitrile electrolyte. Power specifications and minimal price of H₂-O₂ fuel cells are limited by the expensive platinum-based catalysts. The main direction in development of non-platinum catalysts for the oxygen reduction is the study of cheap porous carbonaceous materials which can be obtained by the pyrolysis of polymers including renewable biomass. It is known that nitrogen atoms in carbon materials to a high degree determine properties of the doped activated carbons, such as high electrochemical stability, hardness, electric resistance, etc. The lack of sufficient knowledge on the doping of the carbon materials calls for the ongoing researches of properties and structure of modified carbon matrix. In the second part of this study, highly porous activated carbons were synthesized using alkali thermochemical activation from wood, cellulose and cellulose production residues – craft lignin and sewage sludge. Activated carbon samples were doped with dicyandiamide and melamine for the application as fuel cell cathodes. Conditions of nitrogen introduction (solvent, treatment temperature) and its content in the carbonaceous material, as well as porous structure characteristics, such as specific surface and pore size distribution, were studied. It was found that efficiency of doping reaction depends on the elemental oxygen content in the activated carbon. Relationships between nitrogen content, porous structure characteristics and electrodes electrochemical properties are demonstrated.

Keywords: activated carbons, low-temperature fuel cells, nitrogen doping, porous structure, supercapacitors

Procedia PDF Downloads 92

Authors: Anja I. Petrov, Milica B. Veljković, Marija M. Ćorović, Ana D. Milivojević, Milica B. Simović, Katarina M. Banjanac, Dejan I. Bezbradica

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One of the fundamental requirements for overall human well-being is a stable and balanced microbiome. Aside from the microorganisms that reside within the body, a large number of microorganisms, especially bacteria, swarming the human skin is in homeostasis with the host and represents a skin microbiota. Even though the immune system of the skin is capable of distinguishing between commensal and potentially harmful transient bacteria, the cutaneous microbial balance can be disrupted under certain circumstances. In that case, a reduction in the skin microbiota diversity, as well as changes in metabolic activity, results in dermal infections and inflammation. Probiotics and prebiotics have the potential to play a significant role in the treatment of these skin disorders. The most common resident bacteria found on the skin, Staphylococcus epidermidis, can act as a potential skin probiotic, contributing to the protection of healthy skin from pathogen colonization, such as Staphylococcus aureus, which is related to atopic dermatitis exacerbation. However, as it is difficult to meet regulations in cosmetic products, another therapy approach could be topical prebiotic supplementation of the skin microbiota. In recent research, polyphenols are attracting scientists' interest as biomolecules with possible prebiotic effects on the skin microbiota. This research aimed to determine how herbal extracts rich in different polyphenolic compounds (lemon balm, St. John's wort, coltsfoot, pine needle, and yarrow) affected the growth of S. epidermidis and S. aureus. The first part of the study involved screening plants to determine if they could be regarded as probable candidates to be skin prebiotics. The effect of each plant on bacterial growth was examined by supplementing the nutrient medium with their extracts and comparing it with control samples (without extract). The results obtained after 24 h of incubation showed that all tested extracts influenced the growth of the examined bacteria to some extent. Since lemon balm and St. John's wort extracts displayed bactericidal activity against S. epidermidis, whereas coltsfoot inhibited both bacteria equally, they were not explored further. On the other hand, pine needles and yarrow extract led to an increase in S. epidermidis/S. aureus ratio, making them prospective candidates to be used as skin prebiotics. By examining the prebiotic effect of two extracts at different concentrations, it was revealed that, in the case of yarrow, 0.1% of extract dry matter in the fermentation medium was optimal, while for the pine needle extract, a concentration of 0.05% was preferred, since it selectively stimulated S. epidermidis growth and inhibited S. aureus proliferation. Additionally, the total polyphenols and flavonoid content of the two extracts were determined, revealing different concentrations and polyphenol profiles. Since yarrow and pine extracts affected the growth of skin bacteria in a dose-dependent manner, by carefully selecting the quantities of these extracts, and thus polyphenols content, it is possible to achieve desirable alterations of skin microbiota composition, which may be suitable for the treatment of atopic dermatitis.

Keywords: herbal extracts, polyphenols, skin microbiota, skin prebiotics

Procedia PDF Downloads 140

Authors: Dmitriy Yu. Korulkin, Raissa A. Muzychkina

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The last decade the growth of severe and disseminated forms of inflammatory diseases is observed in Kazakhstan, in particular, septic shock, which progresses on 3-15% of patients with infectious complications of postnatal period. In terms of the rate of occurrence septic shock takes third place after hemorrhagic and cardiovascular shock, in terms of lethality it takes first place. The structure of obstetric sepsis has significantly changed. Currently the first place is taken by postabortive sepsis (40%) that is connected with usage of imperfect methods of artificial termination of pregnancy in late periods (intraamnial injection of sodium chloride, glucose). The second place is taken by postnatal sepsis (32%); the last place is taken by septic complications of caesarean section (28%). In this connection, search for and assessment of effectiveness of new medicines for treatment of postoperative infectious complications, having biostimulating effect and speeding up regeneration processes, is very promising and topical. Essential oil was obtained by the method hydrodistillation air-dry aerial part of Sedum L. plants using Clevenger apparatus. Pilot batch of plant medicinal product based on Sedum essential oils was produced by Chimpharm JSC, Santo Member of Polpharma Group (Kazakhstan). During clinical test of the plant medicinal product based on Sedum L. essential oils 37 female patients at the age from 35 to 57 with clinical signs of complicated postoperative processes and 12 new mothers with clinical signs of inflammatory process on sutures on anterior abdominal wall after caesarean section and partial disruption of surgical suture line on perineum were examined. Medicine usage methods - surgical wound treatment 2 times a day, treatment with other medicines of local action was not performed. Before and after treatment general clinical test, determination of immune status, bacterioscopic test of wound fluid was performed to all women, medical history data was taken into account, wound cleansing and healing time, full granulations, side effects and complications, satisfaction with the used medicine was assessed. On female patients with inflammatory infiltration and partial disruption of surgical suture line anesthetic wound healing effect of plant medicinal product based on Sedum L. essential oils was observed as early as on the second day after beginning of using it, wound cleansing took place, as a rule, within the first row days. Hyperemia in the area of suture line also was not observed for 2-3-d day of usage of medicine, good constant course was observed. The absence of clinical effect on this group of patients was not registered. The represented data give evidence of that clinical effect was accompanied with normalization of changed laboratory findings. No allergic responses or side effects were observed during usage of the plant medicinal products based on Sedum L. essential oils.

Keywords: antiinflammatory, bioactive substances, essential oils, isolation, sedum L., wound healing

Procedia PDF Downloads 239

Authors: Shelley Y. Hawkins

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Introduction/Background: As technology has grown exponentially in healthcare, nurse educators must prepare Advanced Practice Registered Nurse (APRN) graduates with the knowledge and skills in information systems/technology to support and improve patient care and health care systems. APRN’s are expected to lead in caring for populations who lack accessibility and availability through the use of technology, specifically telehealth. The capacity to effectively and efficiently use technology in patient care delivery is clearly delineated in the American Association of Colleges of Nursing (AACN) Doctor of Nursing Practice (DNP) and Master of Science in Nursing (MSN) Essentials. However, APRN’s have minimal, or no, exposure to formalized telehealth education and lack necessary technical skills needed to incorporate telehealth into their patient care. APRN’s must successfully master the technology using telehealth/telemedicine, electronic health records, health information technology, and clinical decision support systems to advance health. Furthermore, APRN’s must be prepared to lead the coordination and collaboration with other healthcare providers in their use and application. Aim/Goal/Purpose: The purpose of this presentation is to establish and operationalize telehealth-focused educational partnerships between one University School of Nursing and two health care systems in order to enhance the preparation of APRN NP students for practice, teaching, and/or scholarly endeavors. Methods: The proposed project was initially presented by the project director to selected multidisciplinary stakeholders including leadership, home telehealth personnel, primary care providers, and decision support systems within two major health care systems to garner their support for acceptance and implementation. Concurrently, backing was obtained from key university-affiliated colleagues including the Director of Simulation and Innovative Learning Lab and Coordinator of the Health Care Informatics Program. Technology experts skilled in design and production in web applications and electronic modules were secured from two local based technology companies. Results: Two telehealth-focused APRN Program academic/practice partnerships have been established. Students have opportunities to engage in clinically based telehealth experiences focused on: (1) providing patient care while incorporating various technology with a specific emphasis on telehealth; (2) conducting research and/or evidence-based practice projects in order to further develop the scientific foundation regarding incorporation of telehealth with patient care; and (3) participating in the production of patient-level educational materials related to specific topical areas. Conclusions: Evidence-based APRN student telehealth clinical experiences will assist in preparing graduates who can effectively incorporate telehealth into their clinical practice. Greater access for diverse populations will be available as a result of the telehealth service model as well as better care and better outcomes at lower costs. Furthermore, APRN’s will provide the necessary leadership and coordination through interprofessional practice by transforming health care through new innovative care models using information systems and technology.

Keywords: academic/practice partnerships, advanced practice nursing, nursing education, telehealth

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Authors: Mareike Dornhoefer, Madjid Fathi

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Water supply and water quality are key problems of mankind at the moment and - due to increasing population - in the future. Management disciplines like water, environment and quality management therefore need to closely interact, to establish a high level of water quality and to guarantee water supply in all parts of the world. Groundwater remediation is one aspect in this process. From a knowledge management perspective it is only possible to solve complex ecological or environmental problems if different factors, expert knowledge of various stakeholders and formal regulations regarding water, waste or chemical management are interconnected in form of a knowledge base. In general knowledge management focuses the processes of gathering and representing existing and new knowledge in a way, which allows for inference or deduction of knowledge for e.g. a situation where a problem solution or decision support are required. A knowledge base is no sole data repository, but a key element in a knowledge based system, thus providing or allowing for inference mechanisms to deduct further knowledge from existing facts. In consequence this knowledge provides decision support. The given paper introduces an environmental knowledge system in water management. The proposed environmental knowledge system is part of a research concept called Green Knowledge Management. It applies semantic technologies or concepts such as ontology or linked open data to interconnect different data and information sources about environmental aspects, in this case, water quality, as well as background material enriching an established knowledge base. Examples for the aforementioned ecological or environmental factors threatening water quality are among others industrial pollution (e.g. leakage of chemicals), environmental changes (e.g. rise in temperature) or floods, where all kinds of waste are merged and transferred into natural water environments. Water quality is usually determined with the help of measuring different indicators (e.g. chemical or biological), which are gathered with the help of laboratory testing, continuous monitoring equipment or other measuring processes. During all of these processes data are gathered and stored in different databases. Meanwhile the knowledge base needs to be established through interconnecting data of these different data sources and enriching its semantics. Experts may add their knowledge or experiences of previous incidents or influencing factors. In consequence querying or inference mechanisms are applied for the deduction of coherence between indicators, predictive developments or environmental threats. Relevant processes or steps of action may be modeled in form of a rule based approach. Overall the environmental knowledge system supports the interconnection of information and adding semantics to create environmental knowledge about water environment, supply chain as well as quality. The proposed concept itself is a holistic approach, which links to associated disciplines like environmental and quality management. Quality indicators and quality management steps need to be considered e.g. for the process and inference layers of the environmental knowledge system, thus integrating the aforementioned management disciplines in one water management application.

Keywords: water quality, environmental knowledge system, green knowledge management, semantic technologies, quality management

Procedia PDF Downloads 193

Authors: Brad Fox

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Between something and nothing, a bit of both, neither/nor, a figment of the imagination, the womb of the universe - questions of what matter is, where it exists and what it means continue to surge up from the bottom of our concepts and theories. This paper looks at divergences and convergences, intimations and mistranslations, in a lineage of thought that begins with Plato’s Timaeus, travels through Arabic Spain and Syria, finally to end up in the language of science. Up to the 13th century, philosophers in Christian France based such inquiries on a questionable and fragmented translation of the Timaeus by Calcidius, with a commentary that conflated the Platonic concept of khora (‘space’ or ‘void’) with Aristotle’s hyle (‘primal matter’ as derived from ‘wood’ as a building material). Both terms were translated by Calcidius as silva. For 700 years, this was the only source for philosophers of matter in the Latin-speaking world. Bernard Silvestris, in his Cosmographia, exemplifies the concepts developed before new translations from Arabic began to pour into the Latin world from such centers as the court of Toledo. Unlike their counterparts across the Pyrenees, 13th century philosophers in Muslim Spain had access to a broad vocabulary for notions of primal matter. The prolific and visionary theologian, philosopher, and poet Muhyiddin Ibn Arabi could draw on the Ikhwan Al-Safa’s 10th Century renderings of Aristotle, which translated the Greek hyle as the everyday Arabic word maddah, still used for building materials today. He also often used the simple transliteration of hyle as hayula, probably taken from Ibn Sina. The prophet’s son-in-law Ali talked of dust in the air, invisible until it is struck by sunlight. Ibn Arabi adopted this dust - haba - as an expression for an original metaphysical substance, nonexistent but susceptible to manifesting forms. Ibn Arabi compares the dust to a phoenix, because we have heard about it and can conceive of it, but it has no existence unto itself and can be described only in similes. Elsewhere he refers to it as quwwa wa salahiyya - pure potentiality and readiness. The final portion of the paper will compare Bernard and Ibn Arabi’s notions of matter to the recent ontology developed by theoretical physicist and philosopher Karen Barad. Looking at Barad’s work with the work of Nils Bohr, it will argue that there is a rich resonance between Ibn Arabi’s paradoxical conceptions of matter and the quantum vacuum fluctuations verified by recent lab experiments. The inseparability of matter and meaning in Barad recall Ibn Arabi’s original response to Ibn Rushd’s question: Does revelation offer the same knowledge as rationality? ‘Yes and No,’ Ibn Arabi said, ‘and between the yes and no spirit is divided from matter and heads are separated from bodies.’ Ibn Arabi’s double affirmation continues to offer insight into our relationship to momentary experience at its most fundamental level.

Keywords: Karen Barad, Muhyiddin Ibn Arabi, primal matter, Bernard Silvestris

Procedia PDF Downloads 398

Authors: Marcelo Lopes Dias Kolling, Felipe Ferreira Laranjeira, Guilherme Augusto Hettwer, Pedro Salomão Piccinini, Marwan Masri, Carlos Oscar Uebel

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Introduction: Injectable fillers are among the most common nonsurgical cosmetic procedures, with significant growth yearly. Knowledge of rheological and mechanical characteristics of fillers, facial anatomy, and injection technique is essential for safety. Concepts such as the use of cannula versus needle, aspiration before injection, and facial danger zones have been well discussed. In case of an accidental intravascular puncture, the pressure inside the vessel may not be sufficient to push blood into the syringe due to the characteristics of the filler product; this is especially true for calcium hydroxyapatite (CaHA) or hyaluronic acid (HA) fillers with high G’. Since viscoelastic properties of normal saline are much lower than those of fillers, aspiration with saline prior to filler injection may decrease the risk of a false negative aspiration and subsequent catastrophic effects. We discuss a technique to add an additional safety step to the procedure with saline aspiration prior to injection, a ‘’reverse Seldinger’’ technique for intravascular access, which we term SANIT: Saline Aspiration Negative Intravascular Test. Objectives: To demonstrate the author’s (PSP) technique which adds an additional safety step to the process of filler injection, with both CaHA and HA, in order to decrease the risk of intravascular injection. Materials and Methods: Normal skin cleansing and topical anesthesia with prilocaine/lidocaine cream are performed; the facial subunits to be treated are marked. A 3mL Luer lock syringe is filled with 2mL of 0.9% normal saline and a 27G needle, which is turned one half rotation. When a cannula is to be used, the Luer lock syringe is attached to a 27G 4cm single hole disposable cannula. After skin puncture, the 3mL syringe is advanced with the plunger pulled back (negative pressure). Progress is made to the desired depth, all the while aspirating. Once the desired location of filler injection is reached, the syringe is exchanged for the syringe containing a filler, securely grabbing the hub of the needle and taking care to not dislodge the needle tip. Prior to this, we remove 0.1mL of filler to allow for space inside the syringe for aspiration. We again aspirate and inject retrograde. SANIT is especially useful for CaHA, since the G’ is much higher than HA, and thus reflux of blood into the syringe is less likely to occur. Results: The technique has been used safely for the past two years with no adverse events; the increase in cost is negligible (only the cost of 2mL of normal saline). Over 100 patients (over 300 syringes) have been treated with this technique. The risk of accidental intravascular puncture has been calculated to be between 1:6410 to 1:40882 syringes among expert injectors; however, the consequences of intravascular injection can be catastrophic even with board-certified physicians. Conclusions: While the risk of intravascular filler injection is low, the consequences can be disastrous. We believe that adding the SANIT technique can help further mitigate risk with no significant untoward effects and could be considered by all performing injectable fillers. Further follow-up is ongoing.

Keywords: injectable fillers, safety, saline aspiration, injectable filler complications, hyaluronic acid, calcium hydroxyapatite

Procedia PDF Downloads 124

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

Procedia PDF Downloads 190

Authors: Lacramioara Ochiuz, Manuela Hortolomei, Aurelia Vasile, Iulian Stoleriu, Marcel Popa, Cristian Peptu

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Local antibiotherapy is one of the most effective acne therapies. Erythromycin (ER) is a macrolide antibiotic topically administered for over 30 years in the form of gel, ointment or hydroalcoholic solution for the acne therapy. The use of ER as a base for topical dosage forms raises some technological challenges due to the physicochemical properties of this substance. The main disadvantage of ER is the poor water solubility (2 mg/mL) that limits both formulation using hydrophilic bases and skin permeability. Cyclodextrins (CDs) are biocompatible cyclic oligomers of glucose, with hydrophobic core and hydrophilic exterior. CDs are used to improve the bioavailability of drugs by increasing their solubility and/or their rate of dissolution after including the poorly water soluble substances (such as ER) in the hydrophobic cavity of CDs. Adding CDs leads to the increase of solubility and improved stability of the drug substance, increased permeability of substances of low water solubility, decreased toxicity and even to active dose reduction as a result of increased bioavailability. CDs increase skin tolerability by reducing the irritant effect of certain substances. We have included ER to lactide modified β-cyclodextrin, in order to improve the therapeutic effect of topically administered ER. The aims of the present study were to synthesise and describe a new complex with prolonged release of ER with lactide modified β-cyclodextrin (CD-LA_E), to investigate the CD-LA_E complex by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR), to analyse the effect of semisolid base on the in vitro and ex vivo release characteristics of ER in the CD-LA_E complex by assessing the permeability coefficient and the release kinetics by fitting on mathematical models. SEM showed that, by complexation, ER changes its crystal structure and enters the amorphous phase. FTIR analysis has shown that certain specific bands of some groups in the ER structure move during the incapsulation process. The structure of the CD-LA_E complex has a molar ratio of 2.12 to 1 between lactide modified β-cyclodextrin and ER. The three semisolid bases (2% Carbopol, 13% Lutrol 127 and organogel based on Lutrol and isopropyl myristate) show a good capacity for incorporating the CD-LA_E complex, having a content of active ingredient ranging from 98.3% to 101.5% as compared to the declared value of 2% ER. The results of the in vitro dissolution test showed that the ER solubility was significantly increased by CDs incapsulation. The amount of ER released from the CD-LA_E gels was in the range of 76.23% to 89.01%, whereas gels based on ER released a maximum percentage of 26.01% ER. The ex vivo dissolution test confirms the increased ER solubility achieved by complexation, and supports the assumption that the use of this process might increase ER permeability. The highest permeability coefficient was obtained in ER released from gel based on 2% Carbopol: in vitro 33.33 μg/cm2/h, and ex vivo 26.82 μg/cm2/h, respectively. The release kinetics of complexed ER is performed by Fickian diffusion, according to the results obtained by fitting the data in the Korsmeyer-Peppas model.

Keywords: erythromycin, acne, lactide, cyclodextrin

Procedia PDF Downloads 232

Authors: Amruta D. S. Pathare, Indira Hinduja, Kusum Zaveri

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Implantation failure (IF) even after the good-quality embryo transfer (ET) in the physiologically normal endometrium is the main obstacle in in vitro fertilization (IVF). Various microarray studies have been performed worldwide to elucidate the genes requisite for endometrial receptivity. These studies have included the population based on different phases of menstrual cycle during natural cycle and stimulated cycle in normal fertile women. Additionally, the literature is also available in recurrent implantation failure patients versus oocyte donors in natural cycle. However, for the first time, we aim to study the genomics of endometrial receptivity in IF patients under controlled ovarian stimulation (COS) during which ET is generally practised in IVF. Endometrial gene expression profiling in IF patients (n=10) and oocyte donors (n=8) were compared during window of implantation under COS by whole genome microarray (using Illumina platform). Enrichment analysis of microarray data was performed to determine dys-regulated biological functions and pathways using Database for Annotation, Visualization and Integrated Discovery, v6.8 (DAVID). The enrichment mapping was performed with the help of Cytoscape software. Microarray results were validated by real-time PCR. Localization of genes related to immune response (Progestagen-Associated Endometrial Protein (PAEP), Leukaemia Inhibitory Factor (LIF), Interleukin-6 Signal Transducer (IL6ST) was detected by immunohistochemistry. The study revealed 418 genes downregulated and 519 genes upregulated in IF patients compared to healthy fertile controls. The gene ontology, pathway analysis and enrichment mapping revealed significant downregulation in activation and regulation of immune and inflammation response in IF patients under COS. The lower expression of Progestagen Associated Endometrial Protein (PAEP), Leukemia Inhibitory Factor (LIF) and Interleukin 6 Signal Transducer (IL6ST) in cases compared to controls by real time and immunohistochemistry suggests the functional importance of these genes. The study was proved useful to uncover the probable reason of implantation failure being imbalance of immune and inflammatory regulation in our group of subjects. Based on the present study findings, a panel of significant dysregulated genes related to immune and inflammatory pathways needs to be further substantiated in larger cohort in natural as well as stimulated cycle. Upon which these genes could be screened in IF patients during window of implantation (WOI) before going for embryo transfer or any other immunological treatment. This would help to estimate the regulation of specific immune response during WOI in a patient. The appropriate treatment of either activation of immune response or suppression of immune response can be then attempted in IF patients to enhance the receptivity of endometrium.

Keywords: endometrial receptivity, immune and inflammatory response, gene expression microarray, window of implantation

Procedia PDF Downloads 115

Authors: Oyedele Ogundana, Amon Simba, Kostas Galanakis, Lynn Oxborrow

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The debate about factors influencing the business growth of women-owned businesses has been a topical issue in business management. Currently, scholars have identified the issues of access to money, market, and management as canvasing factors influencing the business growth of women-owned businesses. However, the influence of motherhood (household/family context) on business growth is inconclusive in the literature; despite that women are more family-oriented than their male counterparts. Therefore, this research study considers the influence of motherhood factor (household/family context) on the business growth of women-owned sewing businesses (WOSBs) in Lagos, Nigeria. The sewing business sector is chosen as the fashion industry (which includes sewing businesses) currently accounts for the second largest number of jobs in Sub-Saharan Africa, following agriculture. Thus, sewing businesses provide a rich ground for contributing to existing scholarly work. Research questions; (1) In what way does the motherhood factor influence the business growth of WOSBs in Lagos? (2) To what extent does the motherhood factor influence the business growth of WOSBs in Lagos? For the method design, a pragmatic approach, a mixed-methods technique and an abductive form of reasoning are adopted. The method design is chosen because it fits, better than other research perspectives, with the research questions posed in this study. For instance, using a positivist approach will not sufficiently answer research question 1, neither will an interpretive approach sufficiently answer research question 2. Therefore, the research method design is divided into 2 phases, and the results from one phase are used to inform the development of the subsequent phases (only phase 1 has been completed at the moment). The first phase uses qualitative data and analytical method to answer research question 1. While the second phase of the research uses quantitative data and analytical method to answer research question 2. For the qualitative phase, 5 WOSBs were purposefully selected and interviewed. The sampling technique is selected as it was not the intention of the researcher to make any statistical inferences, at this phase, rather the purpose was just exploratory. Therefore, the 5 sampled women comprised of 2 unmarried women, 1 married woman with no child, and 2 married women with children. A 40-60 minutes interview was conducted per participants. The interviews were audio-recorded and transcribed. Thereafter, the data were analysed using thematic analysis in order to unearth patterns and relationships. Findings for the first phase of this research reveals that motherhood (household/family context) directly influences (positively/negatively) the performance of WOSBs in Lagos. Apart from a direct influence on WOSBs, motherhood also moderates (positively/negatively) other factors–e.g., access to money, management/human resources and market/opportunities– influencing WOSBs in Lagos. To further strengthen this conclusion, a word frequency query result shows that ‘family,’ ‘husband’ and ‘children’ are among the 10 words used frequently in all the interview transcripts. This first phase contributes to existing studies by showing the various forms by which motherhood influences WOSBs. The second phase (which data are yet to be collected) would reveal the extent to which motherhood influence the business growth of WOSBs in Lagos.

Keywords: women-owned sewing businesses, business growth, motherhood, Lagos

Procedia PDF Downloads 137

Authors: G. Kontochristopoulos, T. Spiliopoulos, V. Markantoni, E. Platsidaki, A. Kouris, E. Balamoti, C. Bokotas, G. Haidemenos

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Introduction: There is a high patient demand for periorbital rejuvenation since the facial area is often the first to show visible signs of aging. With advancing age, there are sometimes marked changes that occur in the skin, fat, muscle and bone of the periorbital region, resulting to wrinkles and skin laxity. These changes are among the easiest areas to correct using several minimally invasive techniques, which have become increasingly popular over the last decade. Lasers, radiofrequency, botulinum toxin, fat grafting and fillers are available treatments sometimes in combination to traditional blepharoplasty. This study attempts to show the benefits of a minimally invasive approach to periorbital wrinkles and skin laxity that combine microneedling and 10% trichloroacetic acid (TCA) peels. Method: Eleven female patients aged 34-72 enrolled in the study. They all gave informed consent after receiving detailed information regarding the treatment procedure. Exclusion criteria in the study were previous treatment for the same condition in the past six months, pregnancy, allergy or hypersensitivity to the components, infection, inflammation and photosensitivity on the affected region. All patients had diffuse periorbital wrinkles and mild to moderate upper or lower eyelid skin laxity. They were treated with Automatic Microneedle Therapy System-Handhold and topical application of 10% trichloroacetic acid solution to each periorbital area for five minutes. Needling at a 0,25 mm depth was performed in both latelar (x-y) directions. Subsequently, the peeling agent was applied to each periorbital area for five minutes. Patients were subjected to the above combination every two weeks for a series of four treatments. Subsequently they were followed up regularly every month for two months. The effect was photo-documented. A Physician's and a Patient's Global Assessment Scale was used to evaluate the efficacy of the treatment (0-25% indicated poor response, 25%-50% fair, 50%-75% good and 75%-100% excellent response). Safety was assessed by monitoring early and delayed adverse events. Results: At the end of the study, almost all patients demonstrated significant aesthetic improvement. Physicians assessed a fair and a good improvement in 9(81.8% of patients) and 2(18.1% of patients) participants respectively. Patients Global Assessment rated a fair and a good response in 6 (54.5%) and 5 (45.4%) participants respectively. The procedure was well tolerated and all patients were satisfied. Mild discomfort and transient erythema were quite common during or immediately after the procedure, however only temporary. During the monthly follow up, no complications or scars were observed. Conclusions: Microneedling is known as a simple, office–based collagen induction therapy. Low concentration TCA solution applied to the epidermis that has been more permeable by microneedling, can reach the dermis more effectively. In the present study, chemical peels with 10% TCA acted as an adjuvant to microneedling, as it causes controlled skin damage, promoting regeneration and rejuvenation of tissues. This combined therapy improved periorbital fine lines, wrinkles, and overall appearance of the skin. Thus it constitutes an alternative treatment of periorbital skin aging, with encouraging results and minor side-effects.

Keywords: chemical peels, microneedling, periorbital wrinkles, skin laxity

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Authors: Ghazal Faraj, András Micsik

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Shapes Constraint Language (SHACL), a World Wide Web Consortium (W3C) language, provides well-defined shapes and RDF graphs, named "shape graphs". These shape graphs validate other resource description framework (RDF) graphs which are called "data graphs". The structural features of SHACL permit generating a variety of conditions to evaluate string matching patterns, value type, and other constraints. Moreover, the framework of SHACL supports high-level validation by expressing more complex conditions in languages such as SPARQL protocol and RDF Query Language (SPARQL). SHACL includes two parts: SHACL Core and SHACL-SPARQL. SHACL Core includes all shapes that cover the most frequent constraint components. While SHACL-SPARQL is an extension that allows SHACL to express more complex customized constraints. Validating the efficacy of dataset mapping is an essential component of reconciled data mechanisms, as the enhancement of different datasets linking is a sustainable process. The conventional validation methods are the semantic reasoner and SPARQL queries. The former checks formalization errors and data type inconsistency, while the latter validates the data contradiction. After executing SPARQL queries, the retrieved information needs to be checked manually by an expert. However, this methodology is time-consuming and inaccurate as it does not test the mapping model comprehensively. Therefore, there is a serious need to expose a new methodology that covers the entire validation aspects for linking and mapping diverse datasets. Our goal is to conduct a new approach to achieve optimal validation outcomes. The first step towards this goal is implementing SHACL to validate the mapping between the International Committee for Documentation (CIDOC) conceptual reference model (CRM) and one of its ontologies. To initiate this project successfully, a thorough understanding of both source and target ontologies was required. Subsequently, the proper environment to run SHACL and its shape graphs were determined. As a case study, we performed SHACL over a CIDOC-CRM dataset after running a Pellet reasoner via the Protégé program. The applied validation falls under multiple categories: a) data type validation which constrains whether the source data is mapped to the correct data type. For instance, checking whether a birthdate is assigned to xsd:datetime and linked to Person entity via crm:P82a_begin_of_the_begin property. b) Data integrity validation which detects inconsistent data. For instance, inspecting whether a person's birthdate occurred before any of the linked event creation dates. The expected results of our work are: 1) highlighting validation techniques and categories, 2) selecting the most suitable techniques for those various categories of validation tasks. The next plan is to establish a comprehensive validation model and generate SHACL shapes automatically.

Keywords: SHACL, CIDOC-CRM, SPARQL, validation of ontology mapping

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Authors: Ankan Roy, Niharika, Samir Kumar Patra

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Anomalous nexus of complex topological assemblies and spatiotemporal epigenetic choreography at chromosomal territory may forms the most sophisticated regulatory layer of gene expression in cancer. Colon cancer is one of the leading malignant neoplasms of the lower gastrointestinal tract worldwide. There is still a paucity of information about the complex molecular mechanisms of colonic cancerogenesis. Bioinformatics prediction and analysis helps to identify essential genes and significant pathways for monitoring and conquering this deadly disease. The present study investigates and explores potential hub genes as biomarkers and effective therapeutic targets for colon cancer treatment. Colon cancer patient sample containing gene expression profile datasets, such as GSE44076, GSE20916, and GSE37364 were downloaded from Gene Expression Omnibus (GEO) database and thoroughly screened using the GEO2R tool and Funrich software to find out common 2 differentially expressed genes (DEGs). Other approaches, including Gene Ontology (GO) and KEGG pathway analysis, Protein-Protein Interaction (PPI) network construction and hub gene investigation, Overall Survival (OS) analysis, gene correlation analysis, methylation pattern analysis, and hub gene-Transcription factors regulatory network construction, were performed and validated using various bioinformatics tool. Initially, we identified 166 DEGs, including 68 up-regulated and 98 down-regulated genes. Up-regulated genes are mainly associated with the Cytokine-cytokine receptor interaction, IL17 signaling pathway, ECM-receptor interaction, Focal adhesion and PI3K-Akt pathway. Downregulated genes are enriched in metabolic pathways, retinol metabolism, Steroid hormone biosynthesis, and bile secretion. From the protein-protein interaction network, thirty hub genes with high connectivity are selected using the MCODE and cytoHubba plugin. Survival analysis, expression validation, correlation analysis, and methylation pattern analysis were further verified using TCGA data. Finally, we predicted COL1A1, COL1A2, COL4A1, SPP1, SPARC, and THBS2 as potential master regulators in colonic cancerogenesis. Moreover, our experimental data highlights that disruption of lipid raft and RAS/MAPK signaling cascade affects this gene hub at mRNA level. We identified COL1A1, COL1A2, COL4A1, SPP1, SPARC, and THBS2 as determinant hub genes in colon cancer progression. They can be considered as biomarkers for diagnosis and promising therapeutic targets in colon cancer treatment. Additionally, our experimental data advertise that signaling pathway act as connecting link between membrane hub and gene hub.

Keywords: hub genes, colon cancer, DNA methylation, epigenetic engineering, bioinformatic predictions

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Authors: Mei Chen, Yingping Hou, Michelle Hao, Soheil Aghamohammadzadeh, Esteban Terzo, Roger Clark, Vijay Modur

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Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genetic skin condition characterized by skin tearing and unremitting blistering upon minimal trauma. Repeated blistering, fibrosis, and scarring lead to aggressive squamous cell carcinoma later in life. RDEB is caused by mutations in the COL7A1 gene encoding collagen type VII (C7), the major component of anchoring fibrils mediating epidermis-dermis adherence. Nonsense mutations in the COL7A1 gene of a subset of RDEB patients leads to premature termination codons (PTC). Similarly, most Junctional Epidermolysis Bullosa (JEB) cases are caused by nonsense mutations in the LAMB3 gene encoding the β3 subunit of laminin 332. Currently, there is an unmet need for the treatment of RDEB and JEB. Zikani Therapeutics has discovered an array of macrocyclic compounds with ring structures similar to macrolide antibiotics that can facilitate readthrough activity of nonsense mutations in the COL7A1 and LAMB3 genes by acting as Ribosome Modulating Agents (RMAs). The medicinal chemistry synthetic advancements of these macrocyclic compounds have allowed targeting the human ribosome while preserving the structural elements responsible for the safety and pharmacokinetic profile of clinically used macrolide antibiotics. Methods: C7 expression was used as a measure of readthrough activity by immunoblot assays in two primary human fibroblasts from RDEB patients (R578X/R578X and R163X/R1683X-COL7A1). Similarly, immunoblot assays in C325X/c.629-12T > A-LAMB3 keratinocytes were used to measure readthrough activity for JEB. The relative readthrough activity of each compound was measured relative to Gentamicin. An imaging-based fibroblast migration assay was used as an assessment of C7 functionality in RDEB-fibroblasts over 16-20 hrs. The incubation period for the above experiments was 48 hrs for RDEB fibroblasts and 72 hours for JEB keratinocytes. Results: 9 RMAs demonstrated increased protein expression in both patient RDEB fibroblasts. The highest readthrough activity at tested concentrations without cytotoxicities increased protein expression up to 179% of Gentamicin (400 µg/ml), with favored readthrough activity in R163X/R1683X-COL7A1 fibroblasts. Concurrent with protein expression, fibroblast hypermotility phenotype observed in RDEB was rescued by reducing motility by ~35% to WT levels (the same level as 690 µM Gentamicin treated cells). Laminin β3 expression was also shown to be increased by 6 RMAs in keratinocytes to 33-83% of (400 µg/ml) Gentamicin. Conclusions: To date, 9 RMAs have been identified that enhance the expression of functional C7 in a mutation-dependent manner in two different RDEB patient fibroblast backgrounds (R578X/R578X and R163X/R1683X-COL7A1). A further 6 RMAs have been identified that enhance the readthrough of C325X-LAMB3 in JEB patient keratinocytes. Based on the clinical trial conducted by us with topical gentamycin in 2017, Zikani’s RMAs achieve clinically significant levels of read-through for the treatment of recessive dystrophic and Junctional Epidermolysis Bullosa.

Keywords: epidermolysis bullosa, nonsense mutation, readthrough, ribosome modulation

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Authors: Melanie Grier, Adam Murry

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Objective: Worldwide, Indigenous Peoples experience underemployment and poverty at disproportionately higher rates than non-Indigenous people, despite similar rates of employment seeking. Euro-colonial conquest and genocidal assimilation policies are implicated as perpetuating poverty, which research consistently links to health and wellbeing disparities. Many of the contributors to poverty, such as inadequate income and lack of access to medical care, can be directly or indirectly linked to underemployment. Calls have been made to prioritize Indigenous perspectives in Industrial-Organizational (I/O) psychology research, yet the literature on Indigenous employment remains scarce. What does exist is disciplinarily diverse, topically scattered, and lacking evidence of community-based participatory research (CBPR) practices, a research project approach which prioritizes community leadership, partnership, and betterment and reduces the potential for harm. Due to the harmful colonial legacy of extractive scientific inquiry "on" rather than "with" Indigenous groups, Indigenous leaders and research funding agencies advocate for academic researchers to adopt reparative research methodologies such as CBPR to be used when studying issues pertaining to Indigenous Peoples or individuals. However, the frequency and consistency of CBPR implementation within scholarly discourse are unknown. Therefore, this project’s goal is two-fold: (1) to understand what comprises CBPR in Indigenous research and (2) to determine if CBPR has been historically used in Indigenous employment research. Method: Using a systematic literature review process, sixteen articles about CBPR use with Indigenous groups were selected, and content was analyzed to identify key components comprising CBPR usage. An Indigenous CBPR components framework was constructed and subsequently utilized to analyze the Indigenous employment empirical literature. A similar systematic literature review process was followed to search for relevant empirical articles on Indigenous employment. A total of 120 articles were identified in six global regions: Australia, New Zealand, Canada, America, the Pacific Islands, and Greenland/Norway. Each empirical study was procedurally examined and coded for criteria inclusion using content analysis directives. Results: Analysis revealed that, in total, CBPR elements were used 14% of the time in Indigenous employment research. Most studies (n=69; 58%) neglected to mention using any CBPR components, while just two studies discussed implementing all sixteen (2%). The most significant determinant of overall CBPR use was community member partnership (CP) in the research process. Studies from New Zealand were most likely to use CBPR components, followed by Canada, Australia, and America. While CBPR use did increase slowly over time, meaningful temporal trends were not found. Further, CBPR use did not directly correspond with the total number of topical articles published that year. Conclusions: Community-initiated and engaged research approaches must be better utilized in employment studies involving Indigenous Peoples. Future research efforts must be particularly attentive to community-driven objectives and research protocols, emphasizing specific areas of concern relevant to the field of I/O psychology, such as organizational support, recruitment, and selection.

Keywords: community-based participatory research, content analysis, employment, indigenous research, international, reconciliation, recruitment, reparative research, selection, systematic literature review

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Authors: Laurie Dempsey

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Relationships are considered to be beneficial for emotional wellbeing, happiness and physical health. However, they are also complicated: individuals engage in a multitude of complex and volatile relationships during their lifetime, where the change to or ending of these dynamics can be deeply disruptive. As the internet is further integrated into everyday life and relationships are increasingly mediated, Media Studies’ and Sociology’s research interests intersect and converge. This study longitudinally explores how relationship change over time corresponds with the developing UK technological landscape between 2005-2018. Since the early 2000s, the use of computer-mediated communication (CMC) in the UK has dramatically reshaped interaction. Its use has compelled individuals to renegotiate how they consider their relationships: some argue it has allowed for vast networks to be accumulated and strengthened; others contend that it has eradicated the core values and norms associated with communication, damaging relationships. This research collaborated with UK media regulator Ofcom, utilising the longitudinal dataset from their Adult Media Lives study to explore how relationships and CMC use developed over time. This is a unique qualitative dataset covering 2005-2018, where the same 18 participants partook in annual in-home filmed depth interviews. The interviews’ raw video footage was examined year-on-year to consider how the same people changed their reported behaviour and outlooks towards their relationships, and how this coincided with CMC featuring more prominently in their everyday lives. Each interview was transcribed, thematically analysed and coded using NVivo 11 software. This study allowed for a comprehensive exploration into these individuals’ changing relationships over time, as participants grew older, experienced marriages or divorces, conceived and raised children, or lost loved ones. It found that as technology developed between 2005-2018, everyday CMC use was increasingly normalised and incorporated into relationship maintenance. It played a crucial role in altering relationship dynamics, even factoring in the breakdown of several ties. Three key relationships were identified as being shaped by CMC use: parent-child; extended family; and friendships. Over the years there were substantial instances of relationship conflict: for parents renegotiating their dynamic with their child as they tried to both restrict and encourage their child’s technology use; for estranged family members ‘forced’ together in the online sphere; and for friendships compelled to publicly display their relationship on social media, for fear of social exclusion. However, it was also evident that CMC acted as a crucial lifeline for these participants, providing opportunities to strengthen and maintain their bonds via previously unachievable means, both over time and distance. A longitudinal study of this length and nature utilising the same participants does not currently exist, thus provides crucial insight into how and why relationship dynamics alter over time. This unique and topical piece of research draws together Sociology and Media Studies, illustrating how the UK’s changing technological landscape can reshape one of the most basic human compulsions. This collaboration with Ofcom allows for insight that can be utilised in both academia and policymaking alike, making this research relevant and impactful across a range of academic fields and industries.

Keywords: computer mediated communication, longitudinal research, personal relationships, qualitative data

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Authors: Sami El Khatib, Agnès Leroux, Jean-Louis Merlin, François Guillemin, Marie-Ange D’Hallewin

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Photodynamic therapy (PDT) is a treatment modality based on the cytotoxic effect occurring on the target tissues by interaction of a photosensitizer with light in the presence of oxygen. One of the major advances in PDT can be attributed to the use of topical aminolevulinic (ALA) to induce Protoporphyrin IX (PpIX) for the treatment of early stage cancers as well as diagnosis. ALA is a precursor of the heme synthesis pathway. Locally delivered to the target tissue ALA overcomes the negative feedback exerted by heme and promotes the transient formation of PpIX in situ to reach critical effective levels in cells and tissue. Whereas early steps of the heme pathway occur in the cytosol, PpIX synthesis is shown to be held in the mitochondrial membranes and PpIX fluorescence is expected to accumulate in close vicinity of the initial building site and to progressively diffuse to the neighboring cytoplasmic compartment or other lipophylic organelles. PpIX is known to be highly reactive and will be degraded when irradiated with light. PpIX photobleaching is believed to be governed by a singlet oxygen mediated mechanism in the presence of oxidized amino acids and proteins. PpIX photobleaching and subsequent spectral phototransformation were described widely in tumor cells incubated in vitro with ALA solution, or ex vivo in human and porcine mucosa superfused with hexylaminolevulinate (hALA). PpIX photobleaching was also studied in vivo, using animal models such as normal or tumor mice skin and orthotopic rat bladder model. Hexyl aminolevulinate a more potent lipophilic derivative of ALA was proposed as an adjunct to standard cystoscopy in the fluorescence diagnosis of bladder cancer and other malignancies. We have previously reported the effectiveness of hALA mediated PDT of rat bladder cancer. Although normal and tumor bladder epithelium exhibit similar fluorescence intensities after intravesical instillation of two hALA concentrations (8 and 16 mM), the therapeutic response at 8mM and 20J/cm2 was completely different from the one observed at 16mM irradiated with the same light dose. Where the tumor is destroyed, leaving the underlying submucosa and muscle intact after an 8 mM instillation, 16mM sensitization and subsequent illumination results in the complete destruction of the underlying bladder wall but leaves the tumor undamaged. The object of the current study is to try to unravel the underlying mechanism for this apparent contradiction. PpIX extraction showed identical amounts of photosensitizer in tumor bearing bladders at both concentrations. Photobleaching experiments revealed mono-exponential decay curves in both situations but with a two times faster decay constant in case of 16mM bladders. Fluorescence microscopy shows an identical fluorescence pattern for normal bladders at both concentrations and tumor bladders at 8mM with bright spots. Tumor bladders at 16 mM exhibit a more diffuse cytoplasmic fluorescence distribution. The different response to PDT with regard to the initial pro-drug concentration can thus be attributed to the different cellular localization.

Keywords: bladder cancer, hexyl-aminolevulinate, photobleaching, confocal fluorescence microscopy

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Authors: Valerie Porr, Sydney A. DeCaro

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TARA for borderline personality disorder (BPD), an education and advocacy organization, helps families to compassionately and effectively deal with troubling BPD behaviors. Our psychoeducational programs focus on understanding underlying neurobiological features of BPD and evidence-based methodology integrating dialectical behavior therapy (DBT) and mentalization based therapy (MBT,) clarifying the inherent misunderstanding of BPD behaviors and improving family communication. TARA4BPD conducts online surveys, workshops, and topical webinars. For over 25 years, we have collected data from BPD helpline callers. This data drew our attention to particular childhood idiosyncrasies that seem to characterize many of the children who later met the criteria for BPD. The idiosyncrasies we observed, heightened sensory sensitivity and hypervigilance, were included in Adolf Stern’s 1938 definition of “Borderline.” This aspect of BPD has not been prioritized by personality disorder researchers, presently focused on emotion processing and social cognition in BPD. Parents described sleep reversal problems in infants who, early on, seem to exhibit dysregulation in circadian rhythm. Families describe children as supersensitive to sensory sensations, such as specific sounds, heightened sense of smell, taste, textures of foods, and an inability to tolerate various fabrics textures (i.e., seams in socks). They also exhibit high sensitivity to particular words and voice tones. Many have alexithymia and dyslexia. These children are either hypo- or hypersensitive to sensory sensations, including pain. Many suffer from fibromyalgia. BPD reactions to pain have been studied (C. Schmahl) and confirm the existence of hyper and hypo-reactions to pain stimuli in people with BPD. To date, there is little or no data regarding what comprises a normative range of sensitivity in infants and children. Many parents reported that their children were tested or treated for sensory processing disorder (SPD), learning disorders, and ADHD. SPD is not included in the DSM and is treated by occupational therapists. The overwhelming anecdotal data from thousands of parents of children who later met criteria for BPD led TARA4BPD to develop a sensitivity survey to develop evidence of the possible role of early sensory perception problems as a pre-cursor to BPD, hopefully initiating new directions in BPD research. At present, the research community seems unaware of the role supersensory sensitivity might play as an early indicator of BPD. Parents' observations of childhood sensitivity obtained through family interviews and results of an extensive online survey on sensory responses across various ages of development will be presented. People with BPD suffer from a sense of isolation and otherness that often results in later interpersonal difficulties. Early identification of supersensitive children while brain circuits are developing might decrease the development of social interaction deficits such as rejection sensitivity, self-referential processes, and negative bias, hallmarks of BPD, ultimately minimizing the maladaptive methods of coping with distress that characterizes BPD. Family experiences are an untapped resource for BPD research. It is hoped that this data will give family observations the critical credibility to inform future treatment and research directions.

Keywords: alexithymia, dyslexia, hypersensitivity, sensory processing disorder

Procedia PDF Downloads 171

Authors: Tamar Lin, Nufar Buchshtab, Yifat Elharar, Julian Nicenboim, Rotem Edgar, Iddo Weiner, Lior Zelcbuch, Ariel Cohen, Sharon Kredo-Russo, Inbar Gahali-Sass, Naomi Zak, Sailaja Puttagunta, Merav Bassan

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Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder that is characterized by dry skin and flares of eczematous lesions and intense pruritus. Multiple lines of evidence suggest that AD is associated with increased colonization by Staphylococcus aureus, which contributes to disease pathogenesis through the release of virulence factors that affect both keratinocytes and immune cells, leading to disruption of the skin barrier and immune cell dysfunction. The aim of the current study is to develop a bacteriophage-based product that specifically targets S. aureus. Methods: For the discovery of phage, environmental samples were screened on 118 S. aureus strains isolated from skin samples, followed by multiple enrichment steps. Natural phages were isolated, subjected to Next-generation Sequencing (NGS), and analyzed using proprietary bioinformatics tools for undesirable genes (toxins, antibiotic resistance genes, lysogeny potential), taxonomic classification, and purity. Phage host range was determined by an efficiency of plating (EOP) value above 0.1 and the ability of the cocktail to completely lyse liquid bacterial culture under different growth conditions (e.g., temperature, bacterial stage). Results: Sequencing analysis demonstrated that the 118 S. aureus clinical strains were distributed across the phylogenetic tree of all available Refseq S. aureus (~10,750 strains). Screening environmental samples on the S. aureus isolates resulted in the isolation of 50 lytic phages from different genera, including Silviavirus, Kayvirus, Podoviridae, and a novel unidentified phage. NGS sequencing confirmed the absence of toxic elements in the phages’ genomes. The host range of the individual phages, as measured by the efficiency of plating (EOP), ranged between 41% (48/118) to 79% (93/118). Host range studies in liquid culture revealed that a subset of the phages can infect a broad range of S. aureus strains in different metabolic states, including stationary state. Combining the single-phage EOP results of selected phages resulted in a broad host range cocktail which infected 92% (109/118) of the strains. When tested in vitro in a liquid infection assay, clearance was achieved in 87% (103/118) of the strains, with no evidence of phage resistance throughout the study (24 hours). A S. aureus host was identified that can be used for the production of all the phages in the cocktail at high titers suitable for large-scale manufacturing. This host was validated for the absence of contaminating prophages using advanced NGS methods combined with multiple production cycles. The phages are produced under optimized scale-up conditions and are being used for the development of a topical formulation (BX005) that may be administered to subjects with atopic dermatitis. Conclusions: A cocktail of natural phages targeting S. aureus was effective in reducing bacterial burden across multiple assays. Phage products may offer safe and effective steroid-sparing options for atopic dermatitis.

Keywords: atopic dermatitis, bacteriophage cocktail, host range, Staphylococcus aureus

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Authors: Shivani Dhande, Sanjiv Choudhary, Adarshlata Singh

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Introduction: Chemical peeling is a popular, relatively inexpensive day procedure and generally safe method for treatment of pigmentary skin disorders and for skin rejuvenation. Chemical peels are classified by the depth of action into superficial, medium, and deep peels.Various facial pigmentary conditions have significant impact on quality of life causing psychological stress, necessitating its safe and effective treatment.Aim & Objectives:To compare the efficacy of Salicylic acid, Trichloroaceticacid & Glycolic Acid in facial melanosis(melasma,photomelanosis& post acne pigmentation).To study the side effects of above mentioned peeling agents. Method and Materials:It was a randomized parallel control single blind study consisting of total of 36 cases, 12 cases each of melasma, photo melanosis and post acne pigmentation within age group 20-50 years having fitzpatrick’s skin type4. Woods lamp examination was done to confirm the type of melasma.Patients with keloidal tendency, active herpes infection or past history of hypersensitivity to salicylic acid, trichloroaceticand glycolic acid as well aspatients on systemic isotretinoin were excluded.Clinical photographs at the beginning of therapy and then serially, were taken to assess the clinical response. Prior to application a written informed consent was obtained. A post auricular test peel was performed. Patients were divided into 3 groups, containing 12 patients each of melasma, photomelanosis and post acnepigmentation.All the three peels SA peel 20% (done once in 2 weeks), GA peel 50% (done once in 3 weeks) and TCA 15% (done once in 3 weeks) were used with total six settings for each patient. Before application of peel patients were counseled to wash the face with soap and water. Then face was dried and cleaned with spirit and acetone to remove all cutaneous oils. GA, TCA, SA were applied with cotton buds/gauze withmild strokes. After a contact period off 5-10mins neutralization was done with cold water. Post peel topical sunscreen application was mandatory. MASI was used pre and post treatment to assess melasma. Investigator’s global improvement scale- overall hyperpigmentation (4-significant, 3-moderate, 2-mild, 1-minimal, 0-no change ) and Patient’s satisfaction grading scale (>70%- excellent response, 50-70%- good response, <50%- average response) was used to assess improvement in all the three facial melanosis.Results:In our study of 12 patients of melasma, 4 (33.33%)patients showed excellent results;3 (25%) with GAand 1(8.33%) of TCA.Good response was seen in 4 (33.33%) patients;1(8.33%) each for GA & SA and 2(16.66%) for TCA.Poor response was seen in 4(33.33%) patients;1(8.33%) for TCA and 3 (25%) for SA.Of 12 patients of photomelanosis, excellent resultswas seen in 3(25%)patients of TCA. Good response was seen in 4 (33.33%) patients, 1(8.33%) each of TCA &SA and 2(16.66%) of GA.Poor responsewas seen in 5(41.66%) patients;3 (25%) for SA and 2(16.66%) of GA.Of 12 patients of post acne pigmentation, excellent responsein 3 (25%) patients;2(16.66%) of SA and 1(8.33%) of TCA.Good responsewas seen in 5(41.66%) patients;2(16.66%) of SA and GA and1(8.33%) of TCA.Poor response was seen in 4 (33.33%) patients; 2 (16.66%) for SA and TCA both. No major side effects in the form of scarring or persistant pigmentation was seen. Transient blackening of skin with burning sensation was seen in cases treated with TCA and SA. Post procedural itching and redness was noted with GA peel. Conclusion- In our study GA(50%),TCA(15%) & SA(20%) peels showed excellent response in melasma, photomelanosis and post-acne pigmentation respectively.All the 3 peeling agents were well tolerated without any significant side-effects in the above specified concentrations.

Keywords: facial melanosis, gycolic acid, salicylic acid, trichloroacetic acid

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Authors: Veenu Bala, Yashpal S. Chhonker, Bhavana Kushwaha, Rabi S. Bhatta, Gopal Gupta, Vishnu L. Sharma

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According to UNAIDS 2013 estimate nearly 52% of all individuals living with HIV are now women of reproductive age (15–44 years). Seventy-five percent cases of HIV acquisition are through heterosexual contacts and sexually transmitted infections (STIs), attributable to unsafe sexual behaviour. Each year, an estimated 500 million people acquire atleast one of four STIs: chlamydia, gonorrhoea, syphilis and trichomoniasis. Trichomonas vaginalis (TV) is exclusively sexually transmitted in adults, accounting for 30% of STI cases and associated with pelvic inflammatory disease (PID), vaginitis and pregnancy complications in women. TV infection resulted in impaired vaginal milieu, eventually favoring HIV transmission. In the absence of an effective prophylactic HIV vaccine, prevention of new infections has become a priority. It was thought worthwhile to integrate HIV prevention and reproductive health services including unintended pregnancy protection for women as both are related with unprotected sex. Initially, nonoxynol-9 (N-9) had been proposed as a spermicidal agent with microbicidal activity but on the contrary it increased HIV susceptibility due to surfactant action. Thus, to accomplish an urgent need of novel woman controlled non-detergent microbicidal spermicides benzenepropanamine analogues have been synthesized. At first, five benzenepropanamine-dithiocarbamate hybrids have been synthesized and evaluated for their spermicidal, anti-Trichomonas and anti-fungal activities along with safety profiling to cervicovaginal cells. In order to further enhance the scope of above study benzenepropanamine was hybridized with thiourea as to introduce anti-HIV potential. The synthesized hybrid molecules were evaluated for their reverse transcriptase (RT) inhibition, spermicidal, anti-Trichomonas and antimicrobial activities as well as their safety against vaginal flora and cervical cells. simulated vaginal fluid (SVF) stability and pharmacokinetics of most potent compound versus N-9 was examined in female Newzealand (NZ) rabbits to observe its absorption into systemic circulation and subsequent exposure in blood plasma through vaginal wall. The study resulted in the most promising compound N-butyl-4-(3-oxo-3-phenylpropyl) piperazin-1-carbothioamide (29) exhibiting better activity profile than N-9 as it showed RT inhibition (72.30 %), anti-Trichomonas (MIC, 46.72 µM against MTZ susceptible and MIC, 187.68 µM against resistant strain), spermicidal (MEC, 0.01%) and antifungal activity (MIC, 3.12–50 µg/mL) against four fungal strains. The high safety against vaginal epithelium (HeLa cells) and compatibility with vaginal flora (lactobacillus), SVF stability and least vaginal absorption supported its suitability for topical vaginal application. Docking study was performed to gain an insight into the binding mode and interactions of the most promising compound, N-butyl-4-(3-oxo-3-phenylpropyl) piperazin-1-carbothioamide (29) with HIV-1 Reverse Transcriptase. The docking study has revealed that compound (29) interacted with HIV-1 RT similar to standard drug Nevirapine. It may be concluded that hybridization of benzenepropanamine and thiourea moiety resulted into novel lead with multiple activities including RT inhibition. A further lead optimization may result into effective vaginal microbicides having spermicidal, anti-Trichomonas, antifungal and anti-HIV potential altogether with enhanced safety to cervico-vaginal cells in comparison to Nonoxynol-9.

Keywords: microbicidal, nonoxynol-9, reverse transcriptase, spermicide

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Authors: Hanan Begali, Shahi Dost, Annett Ziegler, Markus Cornberg, Maria-Esther Vidal, Anke R. M. Kraft

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Chronic hepatitis B virus (HBV) infection can be treated with nucleot(s)ide analog (NA), for example, which inhibits HBV replication. However, they have hardly any influence on the functional cure of HBV, which is defined by hepatitis B surface antigen (HBsAg) loss. NA needs to be taken life-long, which is not available for all patients worldwide. Additionally, NA-treated patients are still at risk of developing cirrhosis, liver failure, or hepatocellular carcinoma (HCC). Although each patient has the same components of the immune system, immune responses vary between patients. Therefore, a deeper understanding of the immune response against HBV in different patients is necessary to understand the parameters leading to HBV cure and to use this knowledge to optimize HBV therapies. This requires seamless integration of an enormous amount of diverse and fine-grained data from viral markers, e.g., hepatitis B core-related antigen (HBcrAg) and hepatitis B surface antigen (HBsAg). The data integration system relies on the assumption that profiling human immune systems requires the analysis of various variables (e.g., demographic data, treatments, pre-existing conditions, immune cell response, or HLA-typing) rather than only one. However, the values of these variables are collected independently. They are presented in a myriad of formats, e.g., excel files, textual descriptions, lab book notes, and images of flow cytometry dot plots. Additionally, patients can be identified differently in these analyses. This heterogeneity complicates the integration of variables, as data management techniques are needed to create a unified view in which individual formats and identifiers are transparent when profiling the human immune systems. The proposed study (HBsRE) aims at integrating heterogeneous data sets of 87 chronically HBV-infected patients, e.g., clinical data, immune cell response, and HLA-typing, with knowledge encoded in biomedical ontologies and open-source databases into a knowledge-driven framework. This new technique enables us to harmonize and standardize heterogeneous datasets in the defined modeling of the data integration system, which will be evaluated in the knowledge graph (KG). KGs are data structures that represent the knowledge and data as factual statements using a graph data model. Finally, the analytic data model will be applied on top of KG in order to develop a deeper understanding of the immune profiles among various patients and to evaluate factors playing a role in a holistic profile of patients with HBsAg level loss. Additionally, our objective is to utilize this unified approach to stratify patients for new effective treatments. This study is developed in the context of the project “Transforming big data into knowledge: for deep immune profiling in vaccination, infectious diseases, and transplantation (ImProVIT)”, which is a multidisciplinary team composed of computer scientists, infection biologists, and immunologists.

Keywords: chronic hepatitis B infection, immune response, knowledge graphs, ontology

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Authors: Anthony F. Peressini

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The concept of race has recently come prominently back into discussion in the context of medicine and medical science, along with renewed effort to biologize racial concepts. This paper argues that this renewed effort to biologize race by way of medicine and population genetics fail on their own terms, and more importantly, that the philosophical project of biologizing race ought to be recognized for what it is—a retrograde racial project—and abandoned. There is clear agreement that standard racial categories and concepts cannot be grounded in the old way of racial naturalism, which understand race as a real, interest-independent biological/metaphysical category in which its members share “physical, moral, intellectual, and cultural characteristics.” But equally clear is the very real and pervasive presence of racial concepts in individual and collective consciousness and behavior, and so it remains a pressing area in which to seek deeper understanding. Recent philosophical work has endeavored to reconcile these two observations by developing a “thin” conception of race, grounded in scientific concepts but without the moral and metaphysical content. Such “thin,” science-based analyses take the “commonsense” or “folk” sense of race as it functions in contemporary society as the starting point for their philosophic-scientific projects to biologize racial concepts. A “philosophic-scientific analysis” is a special case of the cornerstone of analytic philosophy: a conceptual analysis. That is, a rendering of a concept into the more perspicuous concepts that constitute it. Thus a philosophic-scientific account of a concept is an attempt to work out an analysis of a concept that makes use of empirical science's insights to ground, legitimate and explicate the target concept in terms of clearer concepts informed by empirical results. The focus in this paper is on three recent philosophic-scientific cases for retaining “race” that all share this general analytic schema, but that make use of “medical necessity,” population genetics, and human genetic clustering, respectively. After arguing that each of these three approaches suffers from internal difficulties, the paper considers the general analytic schema employed by such biologizations of race. While such endeavors are inevitably prefaced with the disclaimer that the theory to follow is non-essentialist and non-racialist, the case will be made that such efforts are not neutral scientific or philosophical projects but rather are what sociologists call a racial project, that is, one of many competing efforts that conjoin a representation of what race means to specific efforts to determine social and institutional arrangements of power, resources, authority, etc. Accordingly, philosophic-scientific biologizations of race, since they begin from and condition their analyses on “folk” conceptions, cannot pretend to be “prior to” other disciplinary insights, nor to transcend the social-political dynamics involved in formulating theories of race. As a result, such traditional philosophical efforts can be seen to be disciplinarily parochial and to address only a caricature of a large and important human problem—and thereby further contributing to the unfortunate isolation of philosophical thinking about race from other disciplines.

Keywords: population genetics, ontology of race, race-based medicine, racial formation theory, racial projects, racism, social construction

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Authors: Luminiţa Duţică, Gheorghe Duţică

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One of the most powerful language innovation in the twentieth century music was the heterophony–hypostasis of the vertical syntax entered into the sphere of interest of many composers, such as George Enescu, Pierre Boulez, Mauricio Kagel, György Ligeti and others. The heterophonic syntax has a history of its growth, which means a succession of different concepts and writing techniques. The trajectory of settling this phenomenon does not necessarily take into account the chronology: there are highly complex primary stages and advanced stages of returning to the simple forms of writing. In folklore, the plurimelodic simultaneities are free or random and originate from the (unintentional) differences/‘deviations’ from the state of unison, through a variety of ornaments, melismas, imitations, elongations and abbreviations, all in a flexible rhythmic and non-periodic/immeasurable framework, proper to the parlando-rubato rhythmics. Within the general framework of the multivocal organization, the heterophonic syntax in elaborate (academic) version has imposed itself relatively late compared with polyphony and homophony. Of course, the explanation is simple, if we consider the causal relationship between the sound vocabulary elements – in this case, the modalism – and the typologies of vertical organization appropriate for it. Therefore, adding up the ‘classic’ pathway of the writing typologies (monody – polyphony – homophony), heterophony - applied equally to the structures of modal, serial or synthesis vocabulary – reclaims necessarily an own macrotemporal form, in the sense of the analogies enshrined by the evolution of the musical styles and languages: polyphony→fugue, homophony→sonata. Concerned about the prospect of edifying a new musical ontology, the composer Ştefan Niculescu experienced – along with the mathematical organization of heterophony according to his own original methods – the possibility of extrapolation of this phenomenon in macrostructural plan, reaching this way to the unique form of ‘synchrony’. Founded on coincidentia oppositorum principle (involving the ‘one-multiple’ binom), the sound architecture imagined by Ştefan Niculescu consists in one (temporal) model / algorithm of articulation of two sound states: 1. monovocality state (principle of identity) and 2. multivocality state (principle of difference). In this context, the heterophony becomes an (auto)generative mechanism, with macrotemporal amplitude, strategy that will be grown by the composer, practically throughout his creation (see the works: Ison I, Ison II, Unisonos I, Unisonos II, Duplum, Triplum, Psalmus, Héterophonies pour Montreux (Homages to Enescu and Bartók etc.). For the present demonstration, we selected one of the most edifying works of Ştefan Niculescu – Simphony II, Opus dacicum – where the form of (heterophony-)synchrony acquires monumental-symphonic features, representing an emblematic case for the complexity level achieved by this type of vertical syntax in the twentieth century music.

Keywords: heterophony, modalism, serialism, synchrony, syntax

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Authors: Yi-Hao Wong, Li-Li Chan, Chee-Onn Leong, Stephen Ambu, Joon-Wah Mak, Priyasashi Sahu

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Background: Acanthamoeba is a genus of amoebae which lives as a free-living in nature or as a human pathogen that causes severe brain and eye infections. Virulence potential of Acanthamoeba is not constant and can change with growth conditions. DNA methylation, an epigenetic process which adds methyl groups to DNA, is used by eukaryotic cells, including several human parasites to control their gene expression. We used qPCR, siRNA gene silencing, and RNA sequencing (RNA-Seq) to study DNA-methyltransferase gene family (DNMT) in order to indicate the possibility of its involvement in programming Acanthamoeba virulence potential. Methods: A virulence-attenuated Acanthamoeba isolate (designation: ATCC; original isolate: ATCC 50492) was subjected to mouse passages to restore its pathogenicity; a virulence-reactivated isolate (designation: AC/5) was generated. Several established factors associated with Acanthamoeba virulence phenotype were examined to confirm the succession of reactivation process. Differential gene expression of DNMT between ATCC and AC/5 isolates was performed by qPCR. Silencing on DNMT gene expression in AC/5 isolate was achieved by siRNA duplex. Total RNAs extracted from ATCC, AC/5, and siRNA-treated (designation: si-146) were subjected to RNA-Seq for comparative transcriptomic analysis in order to identify the genome-wide effect of DNMT in regulating Acanthamoeba gene expression. qPCR was performed to validate the RNA-Seq results. Results: Physiological and cytophatic assays demonstrated an increased in virulence potential of AC/5 isolate after mouse passages. DNMT gene expression was significantly higher in AC/5 compared to ATCC isolate (p ≤ 0.01) by qPCR. si-146 duplex reduced DNMT gene expression in AC/5 isolate by 30%. Comparative transcriptome analysis identified the differentially expressed genes, with 3768 genes in AC/5 vs ATCC isolate; 2102 genes in si-146 vs AC/5 isolate and 3422 genes in si-146 vs ATCC isolate, respectively (fold-change of ≥ 2 or ≤ 0.5, p-value adjusted (padj) < 0.05). Of these, 840 and 1262 genes were upregulated and downregulated, respectively, in si-146 vs AC/5 isolate. Eukaryotic orthologous group (KOG) assignments revealed a higher percentage of downregulated gene expression in si-146 compared to AC/5 isolate, were related to posttranslational modification, signal transduction and energy production. Gene Ontology (GO) terms for those downregulated genes shown were associated with transport activity, oxidation-reduction process, and metabolic process. Among these downregulated genes were putative genes encoded for heat shock proteins, transporters, ubiquitin-related proteins, proteins for vesicular trafficking (small GTPases), and oxidoreductases. Functional analysis of similar predicted proteins had been described in other parasitic protozoa for their survival and pathogenicity. Decreased expression of these genes in si146-treated isolate may account in part for Acanthamoeba reduced pathogenicity. qPCR on 6 selected genes upregulated in AC/5 compared to ATCC isolate corroborated the RNA sequencing findings, indicating a good concordance between these two analyses. Conclusion: To the best of our knowledge, this study represents the first genome-wide analysis of DNA methylation and its effects on gene expression in Acanthamoeba spp. The present data indicate that DNA methylation has substantial effect on global gene expression, allowing further dissection of the genome-wide effects of DNA-methyltransferase gene in regulating Acanthamoeba pathogenicity.

Keywords: Acanthamoeba, DNA methylation, RNA sequencing, virulence

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Authors: Charalabos Antonatos, Mariza Panoutsopoulou, Georgios K. Georgakilas, Evangelos Evangelou, Yiannis Vasilopoulos

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The extended tissue damage and severe clinical outcomes of autoimmune diseases, accompanied by the high annual costs to the overall health care system, highlight the need for an efficient therapy. Increasing knowledge over the pathophysiology of specific chronic inflammatory diseases, namely Psoriasis (PsO), Inflammatory Bowel Diseases (IBD) consisting of Crohn’s disease (CD) and Ulcerative colitis (UC), and Rheumatoid Arthritis (RA), has provided insights into the underlying mechanisms that lead to the maintenance of the inflammation, such as Tumor Necrosis Factor alpha (TNF-α). Hence, the anti-TNFα biological agents pose as an ideal therapeutic approach. Despite the efficacy of anti-TNFα agents, several clinical trials have shown that 20-40% of patients do not respond to treatment. Nowadays, high-throughput technologies have been recruited in order to elucidate the complex interactions in multifactorial phenotypes, with the most ubiquitous ones referring to transcriptome quantification analyses. In this context, a random effects meta-analysis of available gene expression cDNA microarray datasets was performed between responders and non-responders to anti-TNFα therapy in patients with IBD, PsO, and RA. Publicly available datasets were systematically searched from inception to 10th of November 2020 and selected for further analysis if they assessed the response to anti-TNFα therapy with clinical score indexes from inflamed biopsies. Specifically, 4 IBD (79 responders/72 non-responders), 3 PsO (40 responders/11 non-responders) and 2 RA (16 responders/6 non-responders) datasetswere selected. After the separate pre-processing of each dataset, 4 separate meta-analyses were conducted; three disease-specific and a single combined meta-analysis on the disease-specific results. The MetaVolcano R package (v.1.8.0) was utilized for a random-effects meta-analysis through theRestricted Maximum Likelihood (RELM) method. The top 1% of the most consistently perturbed genes in the included datasets was highlighted through the TopConfects approach while maintaining a 5% False Discovery Rate (FDR). Genes were considered as Differentialy Expressed (DEGs) as those with P ≤ 0.05, |log2(FC)| ≥ log2(1.25) and perturbed in at least 75% of the included datasets. Over-representation analysis was performed using Gene Ontology and Reactome Pathways for both up- and down-regulated genes in all 4 performed meta-analyses. Protein-Protein interaction networks were also incorporated in the subsequentanalyses with STRING v11.5 and Cytoscape v3.9. Disease-specific meta-analyses detected multiple distinct pro-inflammatory and immune-related down-regulated genes for each disease, such asNFKBIA, IL36, and IRAK1, respectively. Pathway analyses revealed unique and shared pathways between each disease, such as Neutrophil Degranulation and Signaling by Interleukins. The combined meta-analysis unveiled 436 DEGs, 86 out of which were up- and 350 down-regulated, confirming the aforementioned shared pathways and genes, as well as uncovering genes that participate in anti-inflammatory pathways, namely IL-10 signaling. The identification of key biological pathways and regulatory elements is imperative for the accurate prediction of the patient’s response to biological drugs. Meta-analysis of such gene expression data could aid the challenging approach to unravel the complex interactions implicated in the response to anti-TNFα therapy in patients with PsO, IBD, and RA, as well as distinguish gene clusters and pathways that are altered through this heterogeneous phenotype.

Keywords: anti-TNFα, autoimmune, meta-analysis, microarrays

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Authors: B.L. España-Sánchez, E. Luna-Hernández, R.A. Mauricio-Sánchez, M.E. Cruz-Soto, F. Padilla-Vaca, R. Muñoz, L. Granados-López, L.R. Ovalle-Flores, J.L. Menchaca-Arredondo, G. Luna-Bárcenas

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Treatment of burn injured has been considered an important clinical problem due to the fluid control and the presence of microorganisms during the healing process. Conventional treatment includes antiseptic techniques, topical medication and surgical removal of damaged skin, to avoid bacterial growth. In order to accelerate this process, different alternatives for tissue regeneration have been explored, including artificial skin, polymers, hydrogels and hybrid materials. Some requirements consider a nonreactive organic polymer with high biocompatibility and skin adherence, avoiding bacterial infections. Chitin-derivative biopolymer such as chitosan (CS) has been used in skin regeneration following third-degree burns. The biological interest of CS is associated with the improvement of tissue cell stimulation, biocompatibility and antibacterial properties. In particular, antimicrobial properties of CS can be significantly increased when is blended with nanostructured materials. Silver-based nanocomposites have gained attention in medicine due to their high antibacterial properties against pathogens, related to their high surface area/volume ratio at nanomolar concentrations. Silver nanocomposites can be blended or synthesized with chitin-derivative biopolymers in order to obtain a biodegradable/antimicrobial hybrid with improved physic-mechanical properties. In this study, nanocomposites based on chitosan/silver nanoparticles (CS/nAg) were synthesized by the in situ chemical reduction method, improving their antibacterial properties against pathogenic bacteria and enhancing the healing process in thermal burn injuries produced in an animal model. CS/nAg was prepared in solution by the chemical reduction method, using AgNO₃ as precursor. CS was dissolved in acetic acid and mixed with different molar concentrations of AgNO₃: 0.01, 0.025, 0.05 and 0.1 M. Solutions were stirred at 95°C during 20 hours, in order to promote the nAg formation. CS/nAg solutions were placed in Petri dishes and dried, to obtain films. Structural analyses confirm the synthesis of silver nanoparticles (nAg) by means of UV-Vis and TEM, with an average size of 7.5 nm and spherical morphology. FTIR analyses showed the complex formation by the interaction of hydroxyl and amine groups with metallic nanoparticles, and surface chemical analysis (XPS) shows low concentration of Ag⁰/Ag⁺ species. Topography surface analyses by means of AFM shown that hydrated CS form a mesh with an average diameter of 10 µm. Antibacterial activity against S. aureus and P. aeruginosa was improved in all evaluated conditions, such as nAg loading and interaction time. CS/nAg nanocomposites films did not show Ag⁰/Ag⁺ release in saline buffer and rat serum after exposition during 7 days. Healing process was significantly enhanced by the presence of CS/nAg nanocomposites, inducing the production of myofibloblasts, collagen remodelation, blood vessels neoformation and epidermis regeneration after 7 days of injury treatment, by means of histological and immunohistochemistry assays. The present work suggests that hydrated CS/nAg nanocomposites can be formed a mesh, improving the bacterial penetration and the contact with embedded nAg, producing complete growth inhibition after 1.5 hours. Furthermore, CS/nAg nanocomposites improve the cell tissue regeneration in thermal burn injuries induced in rats. Synthesis of antibacterial, non-toxic, and biocompatible nanocomposites can be an important issue in tissue engineering and health care applications.

Keywords: antibacterial, chitosan, healing process, nanocomposites, silver

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Authors: William Michael Short

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Semantic Web’ technologies such as the Unified Medical Language System Metathesaurus, SNOMED-CT, and MeSH have been touted as transformational for the way users access online medical and health information, enabling both the automated analysis of natural-language data and the integration of heterogeneous healthrelated resources distributed across the Internet through the use of standardized terminologies that capture concepts and relationships between concepts that are expressed differently across datasets. However, the approaches that have so far characterized ‘semantic bioinformatics’ have not yet fulfilled the promise of the Semantic Web for medical and health information retrieval applications. This paper argues within the perspective of cognitive linguistics and cognitive anthropology that four features of human meaning-making must be taken into account before the potential of semantic technologies can be realized for this domain. First, many semantic technologies operate exclusively at the level of the word. However, texts convey meanings in ways beyond lexical semantics. For example, transitivity patterns (distributions of active or passive voice) and modality patterns (configurations of modal constituents like may, might, could, would, should) convey experiential and epistemic meanings that are not captured by single words. Language users also naturally associate stretches of text with discrete meanings, so that whole sentences can be ascribed senses similar to the senses of words (so-called ‘discourse topics’). Second, natural language processing systems tend to operate according to the principle of ‘one token, one tag’. For instance, occurrences of the word sound must be disambiguated for part of speech: in context, is sound a noun or a verb or an adjective? In syntactic analysis, deterministic annotation methods may be acceptable. But because natural language utterances are typically characterized by polyvalency and ambiguities of all kinds (including intentional ambiguities), such methods leave the meanings of texts highly impoverished. Third, ontologies tend to be disconnected from everyday language use and so struggle in cases where single concepts are captured through complex lexicalizations that involve profile shifts or other embodied representations. More problematically, concept graphs tend to capture ‘expert’ technical models rather than ‘folk’ models of knowledge and so may not match users’ common-sense intuitions about the organization of concepts in prototypical structures rather than Aristotelian categories. Fourth, and finally, most ontologies do not recognize the pervasively figurative character of human language. However, since the time of Galen the widespread use of metaphor in the linguistic usage of both medical professionals and lay persons has been recognized. In particular, metaphor is a well-documented linguistic tool for communicating experiences of pain. Because semantic medical knowledge-bases are designed to help capture variations within technical vocabularies – rather than the kinds of conventionalized figurative semantics that practitioners as well as patients actually utilize in clinical description and diagnosis – they fail to capture this dimension of linguistic usage. The failure of semantic technologies in these respects degrades the efficiency and efficacy not only of medical research, where information retrieval inefficiencies can lead to direct financial costs to organizations, but also of care provision, especially in contexts of patients’ self-management of complex medical conditions.

Keywords: ambiguity, bioinformatics, language, meaning, metaphor, ontology, semantic web, semantics

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