Search results for: oral bacteria

Authors: Sophio Kobauri, Temur Kantaria, Nina Kulikova, David Tugushi, Ramaz Katsarava

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Polymeric nanoparticles-based drug delivery systems and therapeutics have a great potential in the treatment of a numerous diseases, due to they are characterizing the flexible properties which is giving possibility to modify their structures with a complex definition over their structures, compositions and properties. Important characteristics of the polymeric nanoparticles (PNPs) used as drug carriers are high particle’s stability, high carrier capacity, feasibility of encapsulation of both hydrophilic and hydrophobic drugs, and feasibility of variable routes of administration, including oral application and inhalation; NPs are especially effective for intracellular drug delivery since they penetrate into the cells’ interior though endocytosis. A variety of PNPs based drug delivery systems including charged and neutral, degradable and non-degradable polymers of both natural and synthetic origin have been developed. Among these huge varieties the biodegradable PNPs which can be cleared from the body after the fulfillment of their function could be considered as one of the most promising. For intracellular uptake it is highly desirable to have positively charged PNPs since they can penetrate deep into cell membranes. For long-lasting circulation of PNPs in the body it is important they have so called “stealth coatings” to protect them from the attack of immune system of the organism. One of the effective ways to render the PNPs “invisible” for immune system is their PEGylation which represent the process of pretreatment of polyethylene glycol (PEG) on the surface of PNPs. The present work deals with constructing PNPs from amino acid based biodegradable polymers – regular poly(ester amide) (PEA) composed of sebacic acid, leucine and 1,6-hexandiol (labeled as 8L6), cationic PEA composed of sebacic acid, arginine and 1,6-hexandiol (labeled as 8R6), and comb-like co-PEA composed of sebacic acid, malic acid, leucine and 1,6-hexandiol (labeled as PEG-PEA). The PNPs were fabricated using the polymer deposition/solvent displacement (nanoprecipitation) method. The regular PEA 8L6 form stable negatively charged (zeta-potential within 2-12 mV) PNPs of desired size (within 150-200 nm) in the presence of various surfactants (Tween 20, Tween 80, Brij 010, etc.). Blending the PEAs 8L6 and 8R6 gave the 130-140 nm sized positively charged PNPs having zeta-potential within +20 ÷ +28 mV depending 8L6/8R6 ratio. The PEGylating PEA PEG-PEA was synthesized by interaction of epoxy-co-PEA [8L6]0,5-[tES-L6]0,5 with mPEG-amine-2000 The stable and positively charged PNPs were fabricated using pure PEG-PEA as a surfactant. A firm anchoring of the PEG-PEA with 8L6/8R6 based PNPs (owing to a high afinity of the backbones of all three PEAs) provided good stabilization of the NPs. In vitro biocompatibility study of the new PNPs with four different stable cell lines: A549 (human), U-937 (human), RAW264.7 (murine), Hepa 1-6 (murine) showed they are biocompatible. Considering high stability and cell compatibility of the elaborated PNPs one can conclude that they are promising for subsequent therapeutic applications. This work was supported by the joint grant from the Science and Technology Center in Ukraine and Shota Rustaveli National Science Foundation of Georgia #6298 “New biodegradable cationic polymers composed of arginine and spermine-versatile biomaterials for various biomedical applications”.

Keywords: biodegradable poly(ester amide)s, cationic poly(ester amide), pegylating poly(ester amide), nanoparticles

Procedia PDF Downloads 118

Authors: Sajeli A. Begum, Ameer Basha, Kirti Hira, Rukaiyya Khan

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Cyclic dipeptides are simple diketopiperazine derivatives being investigated by several scientists for their biological effects which include anticancer, antimicrobial, haematological, anticonvulsant, immunomodulatory effect, etc. They are potentially active microbial metabolites having been synthesized too, for developing into drug candidates. Cultures of Pseudomonas species have earlier been reported to produce cyclic dipeptides, helping in quorum sensing signals and bacterial–host colonization phenomena during infections, causing cell anti-proliferation and immunosuppression. Fluorescing Pseudomonas species have been identified to secrete lipid derivatives, peptides, pyrroles, phenazines, indoles, aminoacids, pterines, pseudomonic acids and some antibiotics. In the present work, results of investigation on the cyclic dipeptide metabolites secreted by the culture broth of Pseudomonas species as potent pro-inflammatory cytokine inhibitors are discussed. The bacterial strain was isolated from the rhizospheric soil of groundnut crop and identified as Pseudomonas aeruginosa by 16S rDNA sequence (GenBank Accession No. KT625586). Culture broth of this strain was prepared by inoculating into King’s B broth and incubating at 30 ºC for 7 days. The ethyl acetate extract of culture broth was prepared and lyophilized to get a dry residue (EEPA). Lipopolysaccharide (LPS)-induced ELISA assay proved the inhibition of tumor necrosis factor-alpha (TNF-α) secretion in culture supernatant of RAW 264.7 cells by EEPA (IC50 38.8 μg/mL). The effect of oral administration of EEPA on plasma TNF-α level in rats was tested by ELISA kit. The LPS mediated plasma TNF-α level was reduced to 45% with 125 mg/kg dose of EEPA. Isolation of the chemical constituents of EEPA through column chromatography yielded ten cyclic dipeptides, which were characterized using nuclear magnetic resonance and mass spectroscopic techniques. These cyclic dipeptides are biosynthesized in microorganisms by multifunctional assembly of non-ribosomal peptide synthases and cyclic dipeptide synthase. Cyclo (Gly-L-Pro) was found to be more potentially (IC50 value 4.5 μg/mL) inhibiting TNF-α production followed by cyclo (trans-4-hydroxy-L-Pro-L-Phe) (IC50 value 14.2 μg/mL) and the effect was equal to that of standard immunosuppressant drug, prednisolone. Further, the effect was analyzed by determining mRNA expression of TNF-α in LPS-stimulated RAW 264.7 macrophages using quantitative real-time reverse transcription polymerase chain reaction. EEPA and isolated cyclic dipeptides demonstrated diminution of TNF-α mRNA expression levels in a dose-dependent manner under the tested conditions. Also, they were found to control the expression of other pro-inflammatory cytokines like IL-1β and IL-6, when tested through their mRNA expression levels in LPS-stimulated RAW 264.7 macrophages under LPS-stimulated conditions. In addition, significant inhibition effect was found on Nitric oxide production. Further all the compounds exhibited weak toxicity to LPS-induced RAW 264.7 cells. Thus the outcome of the study disclosed the effectiveness of EEPA and the isolated cyclic dipeptides in down-regulating key cytokines involved in pathophysiology of autoimmune diseases.In another study led by the investigators, microbial cyclic dipeptides were found to exhibit excellent antimicrobial effect against Fusarium moniliforme which is an important causative agent of Sorghum grain mold disease. Thus, cyclic dipeptides are emerging small molecular drug candidates for various autoimmune diseases.

Keywords: cyclic dipeptides, cytokines, Fusarium moniliforme, Pseudomonas, TNF-alpha

Procedia PDF Downloads 208

Authors: Magdy I. A. Alshourbagi

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Background: The National Institute for Deafness and Communication Disorders defines idiopathic sudden sensorineural hearing loss as the idiopathic loss of hearing of at least 30 dB across 3 contiguous frequencies occurring within 3 days.The most common clinical presentation involves an individual experiencing a sudden unilateral hearing loss, tinnitus, a sensation of aural fullness and vertigo. The etiologies and pathologies of ISSNHL remain unclear. Several pathophysiological mechanisms have been described including: vascular occlusion, viral infections, labyrinthine membrane breaks, immune associated disease, abnormal cochlear stress response, trauma, abnormal tissue growth, toxins, ototoxic drugs and cochlear membrane damage. The rationale for the use of hyperbaric oxygen to treat ISSHL is supported by an understanding of the high metabolism and paucity of vascularity to the cochlea. The cochlea and the structures within it require a high oxygen supply. The direct vascular supply, particularly to the organ of Corti, is minimal. Tissue oxygenation to the structures within the cochlea occurs via oxygen diffusion from cochlear capillary networks into the perilymph and the cortilymph. . The perilymph is the primary oxygen source for these intracochlear structures. Unfortunately, perilymph oxygen tension is decreased significantly in patients with ISSHL. To achieve a consistent rise of perilymph oxygen content, the arterial-perilymphatic oxygen concentration difference must be extremely high. This can be restored with hyperbaric oxygen therapy. Subject and Methods: A 37 year old man was presented at the clinic with a five days history of muffled hearing and tinnitus of the right ear. Symptoms were sudden onset, with no associated pain, dizziness or otorrhea and no past history of hearing problems or medical illness. Family history was negative. Physical examination was normal. Otologic examination revealed normal tympanic membranes bilaterally, with no evidence of cerumen or middle ear effusion. Tuning fork examination showed positive Rinne test bilaterally but with lateralization of Weber test to the left side, indicating right ear sensorineural hearing loss. Audiometric analysis confirmed sensorineural hearing loss across all frequencies of about 70- dB in the right ear. Routine lab work were all within normal limits. Clinical diagnosis of idiopathic sudden sensorineural hearing loss of the right ear was made and the patient began a medical treatment (corticosteroid, vasodilator and HBO therapy). The recommended treatment profile consists of 100% O2 at 2.5 atmospheres absolute for 60 minutes daily (six days per week) for 40 treatments .The optimal number of HBOT treatments will vary, depending on the severity and duration of symptomatology and the response to treatment. Results: As HBOT is not yet a standard for idiopathic sudden sensorineural hearing loss, it was introduced to this patient as an adjuvant therapy. The HBOT program was scheduled for 40 sessions, we used a 12-seat multi place chamber for the HBOT, which was started at day seven after the hearing loss onset. After the tenth session of HBOT, improvement of both hearing (by audiogram) and tinnitus was obtained in the affected ear (right). Conclusions: In conclusion, HBOT may be used for idiopathic sudden sensorineural hearing loss as an adjuvant therapy. It may promote oxygenation to the inner ear apparatus and revive hearing ability. Patients who fail to respond to oral and intratympanic steroids may benefit from this treatment. Further investigation is warranted, including animal studies to understand the molecular and histopathological aspects of HBOT and randomized control clinical studies.

Keywords: idiopathic sudden sensorineural hearing loss (issnhl), hyperbaric oxygen therapy (hbot), the decibel (db), oxygen (o2)

Procedia PDF Downloads 430

Authors: Odina Omonjonova

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The Uzbek people have a rich history and a rapidly developing music culture for several centuries. Monuments, shrines, places of culture and spirituality, which are the most beautiful proofs of history, show that this country has been a center of wisdom since ancient times. Nowadays, Uzbekistan is opening its face to the world with its unique spiritual heritage, historical monuments, peaceful corners and beautiful landscapes. Tourists from many countries visit and get acquainted with Uzbek culture and history and acknowledge it with great respect. The place of traditional music in describing the national color on the world scale is incomparable. Oral folk works that have reached this period, lapar, yalla, songs and ‘Shashmaqom’ are the intangible spiritual wealth of the Uzbek people. They embody the ancient and great history, spiritual world, artistic philosophy, spirit and values of our nation. National music is the main part of the culture of the nation, and here it is worth emphasizing the importance of music in the tourism of Uzbekistan. Foreign guests can enjoy our national music in various ways: (1) Concerts: There are many concert halls and cultural centers in the cities of Uzbekistan, where many concerts and events are held. Well-known musicians, singers and ensembles add more beauty to the beauty of these places, performing musical samples in Shashmaqom and other traditional styles. In these concert programs, tourists will have the opportunity to listen to works of art in an attractive live performance. (2) Festivals: Many music festivals are held in Uzbekistan throughout the year. The ‘Sharq Taronalari’ international music festival is a unique holiday where musicians from all over the world gather to celebrate the diversity of musical traditions. In recent years, traditional music has been played regularly in a number of festivals such as the ‘International Maqom Festival’, ‘International Craft Festival’ and ‘Boysun Bahari’ held in our country, which has increased the attention of travelers to our music culture. (3) Cultural seminars. Tourists interested in hands-on musical experience can participate in musical workshops. These classes allow tourists to learn to play traditional musical instruments and even participate in group activities. (4) Street musicians: In the central places and ancient streets of Uzbekistan's cities, we can meet street musicians playing soulful tunes. Performing and singing folklore samples on modern instruments directly attracts foreign guests. In Uzbekistan, national music and tourism have a direct and indirect connection. Music serves as a bridge between the country's history and its modern identity and enriches the travel experience. The impact of national music on tourism goes beyond mere statistics. Although tourist arrivals have increased significantly due to music-related attractions, the real impact lies in the stories and live testimonies of visitors. Travelers often say that the rhythms of Uzbekistan touched their hearts and broadened their worldview. In addition, music tourism strengthens the country's economy, provides employment, supports local artisans and performers, and provides an opportunity to showcase their talents to a global audience. In short, Uzbekistan is not only a place of interest, but it is among the countries that attract travelers with its unique national music. Uzbek music, folklore, songs, from the wonderful melodies of ‘Shashmaqom’ to the attractive sounds of traditional musical instruments, give aesthetic and spiritual pleasure and are important in organizing a large-scale trip for tourists visiting the country.

Keywords: traditional music, folklore, shashmaqom, tourism, festivals, street musicians, traditional musical instruments

Procedia PDF Downloads 34

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

Procedia PDF Downloads 286

Authors: Yogesh Dalvi, Ruby Varghese, Nibu Varghese, C. K. Krishnan Nair

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Introduction: The Genus Phellinus, locally known as Phansomba is a well-known traditional folk medicine. Especially, in Western Ghats of India, many tribes use several species of Phellinus for various ailments related to teeth, throat, tongue, stomach and even wound healing. It is one of the few mushrooms which play a pivotal role in Ayurvedic Dravyaguna. Aim: The present study focuses on to investigate phytochemical analysis, antioxidant, and antitumor (in vitro and in vivo) potential of Phellinus robinae from South India, Kerala Material and Methods: The present study explores the following: 1. Phellinus samples were collected from Ranni, Pathanamthitta district of Kerala state, India from Artocarpus heterophyllus Lam. and species were identified using rDNA region. 2. The fruiting body was shadow dried, powdered and extracted with 50% alcohol using water bath at 60°C which was further condensed by rotary evaporator and lyophilized at minus 40°C temperature. 3. Secondary metabolites were analyzed by using various phytochemical screening assay (Hager’s Test, Wagner’s Test, Sodium hydroxide Test, Lead acetate Test, Ferric chloride Test, Folin-ciocalteu Test, Foaming Test, Benedict’s test, Fehling’s Test and Lowry’s Test). 4. Antioxidant and free radical scavenging activity were analyzed by DPPH, FRAP and Iron chelating assay. 5. The antitumor potential of Water alcohol extract of Phellinus (PAWE) is evaluated through In vitro condition by Trypan blue dye exclusion method in DLA cell line and In vivo by murine model. Result and Discussion: Preliminary phytochemical screening by various biochemical tests revealed presence of a variety of active secondary molecules like alkaloids, flavanoids, saponins, carbohydrate, protein and phenol. In DPPH and FRAP assay PAWE showed significantly higher antioxidant activity as compared to standard Ascorbic acid. While, in Iron chelating assay, PAWE exhibits similar antioxidant activity that of Butylated Hydroxytoluene (BHT) as standard. Further, in the in vitro study, PAWE showed significant inhibition on DLA cell proliferation in dose dependent manner and showed no toxicity on mice splenocytes, when compared to standard chemotherapy drug doxorubicin. In vivo study, oral administration of PAWE showed dose dependent tumor regression in mice and also raised the immunogenicity by restoring levels of antioxidant enzymes in liver and kidney tissue. In both in vitro and in vivo gene expression studies PAWE up-regulates pro-apoptotic genes (Bax, Caspases 3, 8 and 9) and down- regulates anti-apoptotic genes (Bcl2). PAWE also down regulates inflammatory gene (Cox-2) and angiogenic gene (VEGF). Conclusion: Preliminary phytochemical screening revealed that PAWE contains various secondary metabolites which contribute to its antioxidant and free radical scavenging property as evaluated by DPPH, FRAP and Iron chelating assay. PAWE exhibits anti-proliferative activity by the induction of apoptosis through a signaling cascade of death receptor-mediated extrinsic (Caspase8 and Tnf-α), as well as mitochondria-mediated intrinsic (caspase9) and caspase pathways (Caspase3, 8 and 9) and also by regressing angiogenic factor (VEGF) without any inflammation or adverse side effects. Hence, PAWE serve as a potential antioxidant and antitumor agent.

Keywords: antioxidant, antitumor, Dalton lymphoma ascites (DLA), fungi, Phellinus robinae

Procedia PDF Downloads 299

Authors: Sitira Williams, Georgina Cherry, Andrea Wright, Kevin Wells, Taran Rai, Richard Brown, Travis Street, Alasdair Cook

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Social media sources (50) were identified, keywords defined by veterinarians and organised into 6 topics known to be indicative of feline pruritus: body areas, behaviors, symptoms, diagnosis, and treatments. These were augmented using academic literature, a cat owner survey, synonyms, and Google Trends. The content was collected using a social intelligence solution, with keywords tagged and filtered. Data were aggregated and de-duplicated. SL content matching body areas, behaviors and symptoms were reviewed manually, and posts were marked relevant if: posted by a pet owner, identifying an itchy cat and not duplicated. A sub-set of 493 posts published from 2009-2022 was used for reflexive thematic analysis in NVIVO (Burlington, MA) to identify themes. Five themes were identified: allergy, pruritus, additional behaviors, unusual or undesirable behaviors, diagnosis, and treatment. Most (258) posts reported the cat was excessively licking, itching, and scratching. The majority were indoor cats and were less playful and friendly when itchy. Half of these posts did not indicate a known cause of pruritus. Bald spots and scabs (123) were reported, often causing swelling and fur loss, and 56 reported bumps, lumps, and dry patches. Other impacts on the cat’s quality of life were ear mites, cat self-trauma and stress. Seven posts reported their cats’ symptoms caused them ongoing anxiety and depression. Cats with food allergies to poultry (often chicken and beef) causing bald spots featured in 23 posts. Veterinarians advised switching to a raw food diet and/or changing their bowls. Some cats got worse after switching, leaving owners’ needs unmet. Allergic reactions to flea bites causing excessive itching, red spots, scabs, and fur loss were reported in 13 posts. Some (3) posts indicated allergic reactions to medication. Cats with seasonal and skin allergies, causing sneezing, scratching, headshaking, watery eyes, and nasal discharge, were reported 17 times. Eighty-five posts identified additional behaviors. Of these, 13 reported their cat’s burst pimple or insect bite. Common behaviors were headshaking, rubbing, pawing at their ears, and aggressively chewing. In some cases, bites or pimples triggered previously unseen itchiness, making the cat irritable. Twenty-four reported their cat had anxiety: overgrooming, itching, losing fur, hiding, freaking out, breathing quickly, sleeplessness, hissing and vocalising. Most reported these cats as having itchy skin, fleas, and bumps. Cats were commonly diagnosed with an ear infection, ringworm, acne, or kidney disease. Acne was diagnosed in cats with an allergy flare-up or overgrooming. Ear infections were diagnosed in itchy cats with mites or other parasites. Of the treatments mentioned, steroids were most frequently used, then anti-parasitics, including flea treatments and oral medication (steroids, antibiotics). Forty-six posts reported distress following poor outcomes after medication or additional vet consultations. SL provides veterinarians with unique insights. Verbatim comments highlight the detrimental effects of pruritus on pets and owner quality of life. This study demonstrates the need for veterinarians to communicate management and treatment options more effectively to relieve owner frustrations. Data analysis could be scaled up using machine learning for topic modeling.

Keywords: content analysis, feline, itch, pruritus, social media, thematic analysis, veterinary dermatology

Procedia PDF Downloads 186

Authors: Aastha Arora, Vikas Bhuria, Saurabh Singh, Uma Pathak, Shweta Mathur, Puja P. Hazari, Rajat Sandhir, Ravi Soni, Anant N. Bhatt, Bilikere S. Dwarakanath

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Radiotherapy is an effective curative and palliative option for patients with thoracic malignancies. However, lung injury, comprising of pneumonitis and fibrosis, remains a significant clin¬ical complication of thoracic radiation, thus making it a dose-limiting factor. Also, injury to the lung is often reported as part of multi-organ failure in victims of accidental radiation exposures. Radiation induced inflammatory response in the lung, characterized by leukocyte infiltration and vascular changes, is an important contributing factor for the injury. Therefore, countermeasure agents to attenuate radiation induced inflammatory response are considered as an important approach to prevent chronic lung damage. Although Amifostine, the widely used, FDA approved radio-protector, has been found to reduce the radiation induced pneumonitis during radiation therapy of non-small cell lung carcinoma, its application during mass and field exposure is limited due to associated toxicity and ineffectiveness with the oral administration. The amifostine analogue (DRDE-30) overcomes this limitation as it is orally effective in reducing the mortality of whole body irradiated mice. The current study was undertaken to investigate the potential of DRDE-30 to ameliorate radiation induced lung damage. DRDE-30 was administered intra-peritoneally, 30 minutes prior to 13.5 Gy thoracic (60Co-gamma) radiation in C57BL/6 mice. Broncheo- alveolar lavage fluid (BALF) and lung tissues were harvested at 12 and 24 weeks post irradiation for studying inflammatory and fibrotic markers. Lactate dehydrogenase (LDH) leakage, leukocyte count and protein content in BALF were used as parameters to evaluate lung vascular permeability. Inflammatory cell signaling (p38 phosphorylation) and anti-oxidant status (MnSOD and Catalase level) was assessed by Western blot, while X-ray CT scan, H & E staining and trichrome staining were done to study the lung architecture and collagen deposition. Irradiation of the lung increased the total protein content, LDH leakage and total leukocyte count in the BALF, reflecting endothelial barrier dysfunction. These disruptive effects were significantly abolished by DRDE-30, which appear to be linked to the DRDE-30 mediated abrogation of activation of the redox-sensitive pro- inflammatory signaling cascade, the MAPK pathway. Concurrent administration of DRDE-30 with radiation inhibited radiation-induced oxidative stress by strengthening the anti-oxidant defense system and abrogated p38 mitogen-activated protein kinase activation, which was associated with reduced vascular leak and macrophage recruitment to the lungs. Histopathological examination (by H & E staining) of the lung showed radiation-induced inflammation of the lungs, characterized by cellular infiltration, interstitial oedema, alveolar wall thickening, perivascular fibrosis and obstruction of alveolar spaces, which were all reduced by pre-administration of DRDE-30. Structural analysis with X-ray CT indicated lung architecture (linked to the degree of opacity) comparable to un-irradiated mice that correlated well with the lung morphology and reduced collagen deposition. Reduction in the radiation-induced inflammation and fibrosis brought about by DRDE-30 resulted in a profound increase in animal survival (72 % in the combination vs 24% with radiation) observed at the end of 24 weeks following irradiation. These findings establish the potential of the Amifostine analogue, DRDE-30, in reducing radiation induced pulmonary injury by attenuating the inflammatory and fibrotic responses.

Keywords: amifostine, fibrosis, inflammation, lung injury radiation

Procedia PDF Downloads 506

Authors: L. Malic, X. Zhang, D. Brassard, L. Clime, J. Daoud, C. Luebbert, V. Barrere, A. Boutin, S. Bidawid, N. Corneau, J. Farber, T. Veres

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The incidence of infections caused by foodborne pathogens such as Listeria monocytogenes (L. monocytogenes) poses a great potential threat to public health and safety. These issues are further exacerbated by legal repercussions due to “zero tolerance” food safety standards adopted in developed countries. Unfortunately, a large number of related disease outbreaks are caused by pathogens present in extremely low counts currently undetectable by available techniques. The development of highly sensitive and rapid detection of foodborne pathogens is therefore crucial, and requires robust and efficient pre-analytical sample preparation. Immunomagnetic separation is a popular approach to sample preparation. Microfluidic chips combined with external magnets have emerged as viable high throughput methods. However, external magnets alone are not suitable for the capture of nanoparticles, as very strong magnetic fields are required. Devices that incorporate externally applied magnetic field and microstructures of a soft magnetic material have thus been used for local field amplification. Unfortunately, very complex and costly fabrication processes used for integration of soft magnetic materials in the reported proof-of-concept devices would prohibit their use as disposable tools for food and water safety or diagnostic applications. We present a sample preparation magnetic microfluidic device implemented in low-cost thermoplastic polymers using fabrication techniques suitable for mass-production. The developed magnetic capture chip (M-chip) was employed for rapid capture and release of L. monocytogenes conjugated to immunomagnetic nanoparticles (IMNs) in buffer and beef filtrate. The M-chip relies on a dense array of Nickel-coated high-aspect ratio pillars for capture with controlled magnetic field distribution and a microfluidic channel network for sample delivery, waste, wash and recovery. The developed Nickel-coating process and passivation allows generation of switchable local perturbations within the uniform magnetic field generated with a pair of permanent magnets placed at the opposite edges of the chip. This leads to strong and reversible trapping force, wherein high local magnetic field gradients allow efficient capture of IMNs conjugated to L. monocytogenes flowing through the microfluidic chamber. The experimental optimization of the M-chip was performed using commercially available magnetic microparticles and fabricated silica-coated iron-oxide nanoparticles. The fabricated nanoparticles were optimized to achieve the desired magnetic moment and surface functionalization was tailored to allow efficient capture antibody immobilization. The integration, validation and further optimization of the capture and release protocol is demonstrated using both, dead and live L. monocytogenes through fluorescence microscopy and plate- culture method. The capture efficiency of the chip was found to vary as function of listeria to nanoparticle concentration ratio. The maximum capture efficiency of 30% was obtained and the 24-hour plate-culture method allowed the detection of initial sample concentration of only 16 cfu/ml. The device was also very efficient in concentrating the sample from a 10 ml initial volume. Specifically, 280% concentration efficiency was achieved in 17 minutes only, demonstrating the suitability of the system for food safety applications. In addition, flexible design and low-cost fabrication process will allow rapid sample preparation for applications beyond food and water safety, including point-of-care diagnosis.

Keywords: array of pillars, bacteria isolation, immunomagnetic sample preparation, polymer microfluidic device

Procedia PDF Downloads 273

Authors: Pablo Reche

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Since 1980’s aquaculture has become the biggest economic activity in southern Chile, being Salmo salar and Oncorhynchus mykiss the main finfish species. High fish density makes both species prone to contract diseases, what drives the industry to big losses, affecting greatly the local economy. Three are the most concerning infective agents, the infectious salmon anemia virus (ISAv), the bacteria Piscirickettsia salmonis and the copepod Caligus rogercresseyi. To regulate the industry the government arranged the salmon farms within management areas named as barrios, which coordinate the fallowing periods and antibiotics treatments of their salmon farms. In turn, barrios are gathered into larger management areas, named as macrozonas whose purpose is to minimize the risk of disease transmission between them and to enclose the outbreaks within their boundaries. However, disease outbreaks still happen and transmission to neighbor sites enlarges the initial event. Salmon disease agents are mostly transported passively by local currents. Thus, to understand how transmission occurs it must be firstly studied the physical environment. In Chile, salmon farming takes place in the inner seas of the southernmost regions of western Patagonia, between 41.5ºS-55ºS. This coastal marine system is characterised by western winds, latitudinally modulated by the position of the South-Eats Pacific high-pressure centre, high precipitation rates and freshwater inflows from the numerous glaciers (including the largest ice cap out of Antarctic and Greenland). All of these forcings meet in a complex bathymetry and coastline system - deep fjords, shallow sills, narrow straits, channels, archipelagos, inlets, and isolated inner seas- driving an estuarine circulation (fast outflows westwards on surface and slow deeper inflows eastwards). Such a complex system is modelled on the numerical model MIKE3, upon whose 3D current fields particle-track-biological models (one for each infective agent) are decoupled. Each agent biology is parameterized by functions for maturation and mortality (reproduction not included). Such parameterizations are depending upon environmental factors, like temperature and salinity, so their lifespan will depend upon the environmental conditions those virtual agents encounter on their way while passively transported. CLIC (Connectivity-Langrangian–IFOP-Chile) is a service platform that supports the graphical visualization of the connectivity matrices calculated from the particle trajectories files resultant of the particle-track-biological models. On CLIC users can select, from a high-resolution grid (~1km), the areas the connectivity will be calculated between them. These areas can be barrios and macrozonas. Users also can select what nodes of these areas are allowed to release and scatter particles from, depth and frequency of the initial particle release, climatic scenario (winter/summer) and type of particle (ISAv, Piscirickettsia salmonis, Caligus rogercresseyi plus an option for lifeless particles). Results include probabilities downstream (where the particles go) and upstream (where the particles come from), particle age and vertical distribution, all of them aiming to understand how currently connectivity works to eventually propose a minimum risk zonation for aquaculture purpose. Preliminary results in Chiloe inner sea shows that the risk depends not only upon dynamic conditions but upon barrios location with respect to their neighbors.

Keywords: aquaculture zonation, Caligus rogercresseyi, Chilean Patagonia, coastal oceanography, connectivity, infectious salmon anemia virus, Piscirickettsia salmonis

Procedia PDF Downloads 152

Authors: Xu Fei (Philip) WU

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As waste recycling concept been accepted more and more in modern societies, the organic portion of the municipal waste become a sires issue in today’s life. Depend on location and season, the organic waste can bee anywhere between 40-65% of total municipal solid waste. Also composting and anaerobic digestion technologies been applied in this field for years, however both process have difficulties been selected by economical and environmental factors. Beside environmental pollution and risk of virus spread, the compost is not a product been welcomed by people even the waste management has to give up them at no cost. The anaerobic digester has to have 70% of water and keep at 35 degree C or above; base on above conditions, the retention time only can be up to two weeks and remain solid has to be dewater and composting again. The enhancive waste water treatment has to be added after. Because these reasons, the voice of suggesting cancelling recycling program and turning all waste to mass burn incinerations have been raised-A process has already been proved has least energy efficiency and most air pollution problem associated process. A newly developed WXF Bio-energy process employs recently developed and patented pre-designed separation, multi-layer and multi-cavity successive bioreactor landfill technology. It features an improved leachate recycling technology, technologies to maximize the biogas generation rate and a reduced overall turnaround period on the land. A single properly designed and operated site can be used indefinitely. In this process, all collected biogas will be processed to eliminate H2S and other hazardous gases. The methane, carbon dioxide and hydrogen will be utilized in a proprietary process to manufacture methanol which can be sold to mitigate operating costs of the landfill. This integration of new processes offers a more advanced alternative to current sanitary landfill, incineration and compost technology. Xu Fei (Philip) Wu Xu Fei Wu is founder and Chief Scientist of W&Y Environmental International Inc. (W & Y), a Canadian environmental and sustainable energy technology company with patented landfill processes and proprietary waste to energy technologies. He has worked in environmental and sustainable energy fields over the last 25 years. Before W&Y, he worked for Conestoga-Rovers & Associates Limited, Microbe Environmental Science and Technology Inc. of Canada and The Ministry of Nuclear Industry and Ministry of Space Flight Industry of China. Xu Fei Wu holds a Master of Engineering Science degree from The University of Western Ontario. I wish present this paper as an oral presentation only Selected Conference Presentations: • “Removal of Phenolic Compounds with Algae” Presented at 25th Canadian Symposium on Water Pollution Research (CAWPRC Conference), Burlington, Ontario Canada. February, 1990 • “Removal of Phenolic Compounds with Algae” Presented at Annual Conference of Pollution Control Association of Ontario, London, Ontario, Canada. April, 1990 • “Removal of Organochlorine Compounds in a Flocculated Algae Photo-Bioreactor” Presented at International Symposium on Low Cost and Energy Saving Wastewater Treatment Technologies (IAWPRC Conference), Kiyoto, Japan, August, 1990 • “Maximizing Production and Utilization of Landfill Gas” 2009 Wuhan International Conference on Environment(CAWPRC Conference, sponsored by US EPA) Wuhan, China. October, 2009. • “WXF Bio-Energy-A Green, Sustainable Waste to Energy Process” Presented at 9Th International Conference Cooperation for Waste Issues, Kharkiv, Ukraine March, 2012 • “A Lannfill Site Can Be Recycled Indefinitely” Presented at 28th International Conference on solid Waste Technology and Management, Philadelphia, Pennsylvania, USA. March, 2013. Hosted by The Journal of Solid Waste Technology and Management.

Keywords: green fuel, waste management, bio-energy, sustainable development, methanol

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Authors: A. Aceranti, L. Moretti, S. Vernocchi, M. Colorato, P. Caristia

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Irritable bowel syndrome (IBS) is the association between abdominal pain, abdominal distension and intestinal dysfunction for recurring periods. About 10% of the world's population has IBS at any given time in their life, and about 200 people per 100,000 receive an initial diagnosis of IBS each year. Persistent pain is recognized as one of the most pervasive and challenging problems facing the medical community today. Persistent pain is considered more as a complex pathophysiological, diagnostic and therapeutic situation rather than as a persistent symptom. The low efficiency of conventional drug treatments has led many doctors to become interested in the non-drug alternative treatment of IBS, especially for more severe cases. Patients and providers are often dissatisfied with the available drug remedies and often seek complementary and alternative medicine (CAM), a unique and holistic approach to treatment that is not a typical component of conventional medicine. Osteopathic treatment may be of specific interest in patients with IBS. Osteopathy is a complementary health approach that emphasizes the role of the musculoskeletal system in health and promotes optimal function of the body's tissues using a variety of manual techniques to improve body function. Osteopathy has been defined as a patient-centered health discipline based on the principles of interrelation between body structure and function, the body's innate capacity for self-healing and the adoption of a whole person health approach. mainly by practicing manual processing. Studies reported that osteopathic manual treatment (OMT) reduced IBS symptoms, such as abdominal pain, constipation, diarrhea, and improved general well-being. The focus in the treatment of IBS with osteopathy has gone beyond simple spinal alignment, to directly address the abnormal physiology of the body using a series of direct and indirect techniques. The topic of this study was chosen for different reasons: due to the large number of people involved who suffer from this disorder and for the dysfunction itself, since nowadays there is still little clarity about the best type of treatment and, above all, to its origin. The visceral component in the osteopathic field is still a world to be discovered, although it is related to a large part of patient series, it has contents that affect numerous disciplines and this makes it an enigma yet to be solved. The study originated in the didactic practice where the curiosity of a topic is marked that, even today, no one is able to explain and, above all, cure definitively. The main purpose of this study is to try to create a good basis on the osteopathic discipline for subsequent studies that can be exhaustive in the best possible way, resolving some doubts about which treatment modality can be used with more relevance. The path was decided to structure it in such a way that 3 types of osteopathic treatment are used on 3 groups of people who will be selected after completing a questionnaire, which will deem them suitable for the study. They will, in fact, be divided into three groups where: - the first group was given a visceral osteopathic treatment. - The second group was given a manual osteopathic treatment of neurological stimulation. - The third group received a placebo treatment. At the end of the treatment, questionnaires will be re-proposed respectively one week after the session and one month after the treatment from which any data will be collected that will demonstrate the effectiveness or otherwise of the treatment received. The sample of 50 patients examined underwent an oral interview to evaluate the inclusion and exclusion criteria to participate in the study. Of the 50 patients questioned, 17 people who underwent different osteopathic techniques were eligible for the study. Comparing the data related to the first assessment of tenderness and frequency of symptoms with the data related to the first follow-up shows a significant improvement in the score assigned to the different questions, especially in the neurogenic and visceral groups. We are aware of the fact that it is a study performed on a small sample of patients, and this is a penalizing factor. We remain, however, convinced that having obtained good results in terms of subjective improvement in the quality of life of the subjects, it would be very interesting to re-propose the study on a larger sample and fill the gaps.

Keywords: IBS, osteopathy, colon, intestinal inflammation

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Authors: M. H. Pazandeh, M. Doudi, S. Barahimi, L. Rahimzadeh Torabi

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The use of antibiotics is essential in reducing the occurrence of adverse effects and inhibiting the emergence of antibiotic resistance in microbial populations. The necessity for a novel methodology concerning local administration of antibiotics has arisen, with particular focus on dealing with localized infections prompted by bacterial colonization of medical devices or implant materials. Bioactive glasses (BG) are extensively employed in the field of regenerative medicine, encompassing a diverse range of materials utilized for drug delivery systems. In the present investigation, various drug carriers for imipenem and tetracycline, namely single systems BG/SnO2, BG/NiO with varying proportions of metal oxide, and nanocomposite BG/SnO2/NiO, were synthesized through the sol-gel technique. The antibacterial efficacy of the synthesized samples was assessed through the utilization of the disk diffusion method with the aim of neutralizing Staphylococcus aureus as the bacterial model. The current study involved the examination of the bioactivity of two samples, namely BG10SnO2/10NiO and BG20SnO2, which were chosen based on their heightened bacterial inactivation properties. This evaluation entailed the employment of two techniques: the measurement of the pH of simulated body fluid (SBF) solution and the analysis of the sample tablets through X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy. The sample tablets were submerged in SBF for varying durations of 7, 14, and 28 days. The bioactivity of the composite bioactive glass sample was assessed through characterization of alterations in its surface morphology, structure, and chemical composition. This evaluation was performed using scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, and X-ray diffraction spectroscopy. Subsequently, the sample was immersed in simulated liquids to simulate its behavior in biological environments. The specific body fat percentage (SBF) was assessed over a 28-day period. The confirmation of the formation of a hydroxyapatite surface layer serves as a distinct indicator of bioactivity. The infusion of antibiotics into the composite bioactive glass specimen was done separately, and then the release kinetics of tetracycline and imipenem were tested in simulated body fluid (SBF). Antimicrobial effectiveness against various bacterial strains have been proven in numerous instances using both melt and sol-gel techniques to create multiple bioactive glass compositions. An elevated concentration of calcium ions within a solution has been observed to cause an increase in the pH level. In aqueous suspensions, bioactive glass particles manifest a significant antimicrobial impact. The composite bioactive glass specimen exhibits a gradual and uninterrupted release, which is highly desirable for a drug delivery system over a span of 72 hours. The reduction in absorption, which signals the loss of a portion of the antibiotic during the loading process from the initial phosphate-buffered saline solution, indicates the successful bonding of the two antibiotics to the surfaces of the bioactive glass samples. The sample denoted as BG/10SnO2/10NiO exhibits a higher loading of particles compared to the sample designated as BG/20SnO2 in the context of bioactive glass. The enriched sample demonstrates a heightened bactericidal impact on the bacteria under investigation while concurrently preserving its antibacterial characteristics. Tailored bioactive glass that incorporates hydroxyapatite, with a regulated and efficient release of drugs targeting bacterial infections, holds promise as a potential framework for bone implant scaffolds following rigorous clinical evaluation, thereby establishing potential future biomedical uses. During the modification process, the introduction of metal oxides into bioactive glass resulted in improved antibacterial characteristics, particularly in the composite bioactive glass sample that displayed the highest level of efficiency.

Keywords: antibacterial, bioactive glasses, implant infections, multi drug resistant

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Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

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Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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Authors: Charles W. MacQuarrie, Rachel R. Tatro Duarte

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This paper explores the representation of medieval identity within the world of games such as Dragon Age, Elden Ring, Hellblade: Senua’s sacrifice, fantasy role-playing games that draw effectively and problematically on Celtic and Norse mythologies. Focusing on tattoos, onomastics, and accent as visual and oral markers of status and ethnicity, this study analyzes how the game's interplay between mythology, character narratives, and visual storytelling enriches the themes and offers players an immersive, but sometimes baldly ahistorical, connection to ancient mythologies and contemporary digital storytelling. Dragon Age is a triple a game series, Hellblade Senua’s Sacrifice, and Elden Ring of gamers worldwide with its presentation of an idealized medieval world, inspired by the lore of Celtic and Norse mythologies. This paper sets out to explore the intricate relationships between tattoos, accent, and character narratives in the game, drawing parallels to themes,heroic figures and gods from Celtic and Norse mythologies. Tattoos as Mythic and Ethnic Markers: This study analyzes how tattoos in Dragon Age visually represent mythological elements from both Celtic and Norse cultures, serving as conduits of cultural identity and narratives. The nature of these tattoos reflects the slave, criminal, warrior associations made in classical and medieval literature, and some of the episodes concerning tattoos in the games have either close analogs or sources in literature. For example the elvish character Solas, in Dragon Age Inquisition, removes a slave tattoo from the face of a lower status elf in an episode that is reminiscent of Bridget removing the stigmata from Connallus in the Vita Prima of Saint Bridget Character Narratives: The paper examines how characters' personal narratives in the game parallel the archetypal journeys of Celtic heroes and Norse gods, with a focus on their relationships to mythic themes. In these games the Elves usually have Welsh or Irish accents, are close to nature, magically powerful, oppressed by apparently Anglo-Saxon humans and Norse dwarves, and these elves wear facial tattoos. The Welsh voices of fairies and demons is older than the reference in Shakespeare’s Merry Wives of Windsor or even the Anglo-Saxon Life of Saint Guthlac. The English speaking world, and the fantasy genre of literature and gaming, undoubtedly driven by Tolkien, see Elves as Welsh speakers, and as having Welsh accents when speaking English Comparative Analysis: A comparative approach is employed to reveal connections, adaptations, and unique interpretations of the motifs of tattoos and narrative themes in Dragon Age, compared to those found in Celtic and Norse mythologies. Methodology: The study uses a comparative approach to examine the similarities and distinctions between Celtic and Norse mythologies and their counterparts in video games. The analysis encompasses character studies, narrative exploration, visual symbolism, and the historical context of Celtic and Norse cultures. Mythic Visuals: This study showcases how tattoos, as visual symbols, encapsulate mythic narratives, beliefs, and cultural identity, echoing Celtic and Norse visual motifs. Archetypal Journeys: The paper analyzes how character arcs mirror the heroic journeys of Celtic and Norse mythological figures, allowing players to engage with mythic narratives on a personal level. Cultural Interplay: The study discusses how the game's portrayal of tattoos and narratives both preserves and reinterprets elements from Celtic and Norse mythologies, fostering a connection between ancient cultures and modern digital storytelling. Conclusion: By exploring the interconnectedness of tattoos and character narratives in Dragon Age, this paper reveals the game series' ability to act as a bridge between ancient mythologies and contemporary gaming. By drawing inspiration from Celtic heroes and Norse gods and translating them into digital narratives and visual motifs, Dragon Age offers players a multi-dimensional engagement with mythic themes and a unique lens through which to appreciate the enduring allure of these cultures.

Keywords: comparative analysis, character narratives, video games and literature, tattoos, immersive storytelling, character development, mythological influences, Celtic mythology, Norset mythology

Procedia PDF Downloads 64

Authors: Ziyad S. Haidar

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Millions of teeth are removed annually, and dental extraction is one of the most commonly performed surgical procedures globally. Whether due to caries, periodontal disease or trauma, exodontia and the ensuing wound healing and bone remodeling processes of the resultant socket (hole in the jaw bone) usually result in serious deformities of the residual alveolar osseous ridge and surrounding soft tissues (reduced height/width). Such voluminous changes render the placement of a proper conventional bridge, denture or even an implant-supported prosthesis extremely challenging. Further, most extractions continue to be performed with no regard for preventing the onset of alveolar osteitis (also known as dry socket, a painful and difficult-to-treat/-manage condition post-exodontia). Hence, such serious resorptive morphological changes often result in significant facial deformities and a negative impact on the overall Quality of Life (QoL) of patients (and oral health-related QoL), alarming, particularly for the geriatric with compromised healing and in light of the thriving longevity statistics. Opportunity: Despite advances in tissue/wound grafting, serious limitations continue to exist, including efficacy and clinical outcome predictability, cost, treatment time, expertise and risk of immune reactions. For cases of dry sockets, specifically, the commercially-available and often-prescribed home remedies are highly lacking. Indeed, most are not recommended for use anymore. Alveogyl is a fine example. Hence, there is a great market demand and need for alternative solutions. Solution: Herein, SockGEL/PLUG (patent pending), an all-natural, drug-free and injectable stimuli-responsive hydrogel, was designed, formulated, characterized and evaluated as an osteogenic, angiogenic, anti-microbial and pain-soothing suture-free intra-alveolar dressing, safe and efficacious for use in several oro-dental and cranio-maxillo-facial interventional applications; for example: in fresh dental extraction sockets, immediately post-exodontia. It is composed of FDA-approved, biocompatible and biodegradable polymers, self-assembled electro-statically to formulate a scaffolding matrix to (a) prevent the onset of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (b) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. Findings: The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physico-chemico-mechanically for safety (cell viability), viscosity, rheology, bio-distribution and essentially, capacity to induce wound healing and osteogenesis (small defect, in vivo) without any signaling cues from exogenous cells, growth factors or drugs. The performed animal model of cranial critical-sized and non-vascularized bone defects shall provide vitally critical insights into the role and mechanism of the employed natural bio-polymer blend and gel product in endogenous reparative regeneration of soft tissues and bone morphogenesis. Alongside, the fine-tuning of our modified formulation method will further tackle appropriateness, reproducibility, scalability, ease and speed in producing stable, biodegradable and sterilizable stimuli (thermo-sensitive and photo-responsive) matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for an intra-socket application, and beyond. Conclusions and Perspective: Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the bionanomaterial before engaging the market for feasibility, acceptance and cost-effectiveness studies. The SockGEL/PLUG platform is patent pending: SockGEL is a bio-inspired drug-free hydrogel; SockPLUG is a drug-loaded hydrogel designed for complex indications.

Keywords: hydrogel, injectable, dentistry, craniomaxillofacial complex, bioinspired, nanobiotechnology, biopolymer, sol-gel, stimuli-responsive, matrix, tissue engineering, regenerative medicine

Procedia PDF Downloads 67