Search results for: therapeutic culture
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4990

Search results for: therapeutic culture

4270 Layer-by-Layer Coated Dexamethasone Microcrystals for Experimental Inflammatory Bowel Disease Therapy

Authors: Murtada Ahmed Oshi, Jin-Wook Yoo

Abstract:

Layer-by-layer (LBL) coating has gained popularity for drug delivery of therapeutic drugs. Herein we described a novel approach for enhancing the therapeutic efficiency of the locally administered dexamethasone (Dex) for inflammatory bowel disease (IBD). We utilized a LBL-coating technique on Dex microcrystals (DexMCs) with multiple layers of polyelectrolytes composed of poly (allylamine hydrochloride) (PAH), poly (sodium 4-styrene sulfonate) (PSS) and Eudragit® S100 (ES). The successful deposition of the layers onto DexMCs surfaces were confirmed through zeta potential measurement and confocal laser scanning microscopy. The surface morphology was investigated through scanning electron microscopy. The drug encapsulation efficiency was 95% with a mean particle size of 2 µm and negative surface charge (-40 mV). Moreover, in vitro drug release study showed a minimum release of the drug ( 15%) at an acidic condition during initial first 5 h, followed by sustained-release at an alkaline condition. For in vivo study, LBL-DxMCs were administered orally to ICR mice suffering from dextran sulfate sodium-induced colitis. LBL-DxMCs substantially enhanced anti-IBD activities as compared to DxMCs. Macroscopic, histological and biochemical (tumor necrosis factor-α, interleukin-6 and myeloperoxidase) examinations revealed marked improvements of colitis signs in the mice treated with LBL-DxMCs compared with those treated with DxMCs. Overall, LBL-DxMCs could be a suitable candidate for the treatment of IBD.

Keywords: dexamethasone, inflammatory bowel disease, LBL-coating, polyelectrolytes

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4269 Azan in Funeral: A Local Islamic Tradition in Indonesia

Authors: Muhajirin Gafar

Abstract:

In Indonesia, Azan not only used as a reminder or call to prayer, its also used at the birth of a child, as the direction of the Prophet Muhammad PBUH, but also become part of a 'tradition’ to echoed in obsequies or the funeral, even there is a tradition in which the Azan echoed in the four corners of the grave. This tradition has become a necessity and has become part of the local Islamic culture preserved from time to time, although it certainly can not be known legal basis underlying the tradition. Based on the phenomenon, this paper proposed three research objective, namely: 1) To described the history about tradition Azan in funeral, 2) To analyze some of the postulates supporting the occurrence of the tradition, 3) To find out the postulates/ hadist which has been arranged in accordance with the instructions of the Prophet Muhammad PBUH about the rules of funeral. To reconstruct the history of the emergence of events azan tradition in the funeral this research used historical method, while the second and third objective used library research. Data and facts systematically processed and analyzed so as to be able to answer the questions of what, who, where, when, how, and why an event occurred. Finally, this research used Takhrij al-hadith a method to look at the validity of the arguments of the hadith. Result found that tradition of Azan in funeral has been around since the presence of Islam in Indonesia. This tradition continued and became a local Islamic culture which spread almost all over Indonesia, even considered part of religious guidance. While there are no decisive postulates which can be accounted for this tradition, except ‘qiyas’ postulates which are not appropriate. Most Indonesian Muslim put Azan as the first priority to do in funeral while oblivious other compulsory things that must be recited when lay down the corpse. They tend to assume that this tradition is a part of Islamic local culture.

Keywords: Azan, tradition, qiyas, Islamic local, hadist

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4268 Detection and Distribution Pattern of Prevelant Genotypes of Hepatitis C in a Tertiary Care Hospital of Western India

Authors: Upasana Bhumbla

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Background: Hepatitis C virus is a major cause of chronic hepatitis, which can further lead to cirrhosis of the liver and hepatocellular carcinoma. Worldwide the burden of Hepatitis C infection has become a serious threat to the human race. Hepatitis C virus (HCV) has population-specific genotypes and provides valuable epidemiological and therapeutic information. Genotyping and assessment of viral load in HCV patients are important for planning the therapeutic strategies. The aim of the study is to study the changing trends of prevalence and genotypic distribution of hepatitis C virus in a tertiary care hospital in Western India. Methods: It is a retrospective study; blood samples were collected and tested for anti HCV antibodies by ELISA in Dept. of Microbiology. In seropositive Hepatitis C patients, quantification of HCV-RNA was done by real-time PCR and in HCV-RNA positive samples, genotyping was conducted. Results: A total of 114 patients who were seropositive for Anti HCV were recruited in the study, out of which 79 (69.29%) were HCV-RNA positive. Out of these positive samples, 54 were further subjected to genotype determination using real-time PCR. Genotype was not detected in 24 samples due to low viral load; 30 samples were positive for genotype. Conclusion: Knowledge of genotype is crucial for the management of HCV infection and prediction of prognosis. Patients infected with HCV genotype 1 and 4 will have to receive Interferon and Ribavirin for 48 weeks. Patients with these genotypes show a poor sustained viral response when tested 24 weeks after completion of therapy. On the contrary, patients infected with HCV genotype 2 and 3 are reported to have a better response to therapy.

Keywords: hepatocellular, genotype, ribavarin, seropositive

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4267 Prevalence and Pattern of Drug Usage among Youth in Ogbomoso, Nigeria

Authors: Samson F. Agberotimi, Rachel B. Asagba, Choja Oduaran

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Disturbing rate of use of different substances such as cannabis, alcohol, as well as pharmaceutical drugs among Nigerian youth in recent times has been affirmed in the literature. There is, however, a paucity of literature addressing the pattern of usage of such drugs, especially for clinical relevance and intervention planning. The present study investigated the prevalence and pattern of drug usage among youth in Ogbomoso, Nigeria. A cross-sectional survey involving 92 purposively selected participants comprising of 82 males and 10 females aged between 15 and 24 years was conducted. A measure of drug involvement and demographic characteristics was administered to the participants. Descriptive analysis was done using the SPSS v.21. Cannabis (79.4%), alcohol (77.2%), codeine (70.7%), tobacco (65.2%) and tramadol (47.8%) are the five most frequently used substances. However, the majority of the users of tobacco (68.3%) and alcohol (62.0%) are casual users indicating a mild level of use of the substances among the participants. On the other hand, 49.2% of the codeine users, 27.3% of the tramadol users, and 21.9% of the cannabis users reported harmful/intensive levels of use. Furthermore, the results revealed individuals at the pathological level of use as 28.8% for cannabis, 25.0% for tramadol, and 21.6% for codeine, and thus require clinical/therapeutic intervention. In conclusion, cannabis remains the most frequently used substance among youths. However, there appears to be a shift from the use of conventional psychoactive substances to pharmaceutical/prescription drugs such as codeine and tramadol. The findings of this study raised the need for both preventive and therapeutic interventions addressing the problem of substance use disorder among youth in contemporary society.

Keywords: Ogbomoso, pattern of drug use, prevalence of drug use, youth

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4266 Evidence-Based Approaches and Effective Practices for Preventing Bullying

Authors: Nato Asatiani

Abstract:

The research underscores the critical role of a positive school climate in combating bullying. The results can be generalized and assumed that bullying behavior occurs when there is a victim, and the environment allows the realization of aggression; school culture is a strong predictor of bullying behavior; the probability of becoming a victim (victimhood) is high among those teenagers who experience high levels of stress in the environment; when a teenager experiences a sense of threat, such physical, psychological, or social symptoms are developed that makes teenagers vulnerable to bullying; the school culture that is oriented to adherence to the rules of communication and mutual respect in the group reduces the likelihood of a teenager to become a victim; consequently, when a teenager has a sense of wellness even in combination with aggression, this sense reduces the likelihood of a teenager to become a victim.

Keywords: bullying, adolescence, aggression, school climate

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4265 Culture Medium Design Based on Whey for the Growth and Bacteriocin Production of Strains of Pediococcus pentosaceus

Authors: Carolina Gutierrez-Cortes, Hector Suarez, Gustavo Buitrago

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Bacteriocins are antimicrobial peptides produced by bacteria as a competitive strategy for substrate and habitat. Those peptides have a potential use as food biopreservatives due to their antimicrobial activity against foodborne pathogens, avoiding the use of additives that can be harmful to consumers. The industrial production of bacteriocins is currently expensive; one of the options to be competitive is the development of economic culture media, for example, with the use of agro-industrial wastes such as whey. This study evaluated the growth and production of bacteriocins from four strains: Pediococcus pentosaceus 63, Pediococcus pentosaceus 145, Pediococcus pentosaceus 146 and Pediococcus pentosaceus 147 isolated from ‘minas cheese’ (artisanal cheese made from raw milk in the state of Minas Gerais, Brazil) in order to select a strain with growth at high rates and higher antimicrobial activity against Listeria monocytogenes 104 after incubation on the culture medium designed with whey and other components. The media used were: MRS broth, modified MRS broth (using different sources of carbon and nitrogen and different amounts of micronutrients) and a culture medium designed by a factorial design using whey and other components. The final biomass concentrations of the four strains in MRS broth after 24 hours of incubation were very similar 9.25, 9.33, 9.25 and 9.22 (log CFU/mL) for P. pentosaceus 63, P. pentosaceus 145, P. pentosaceus 146 and P. pentosaceus 147 respectively. In the same assays, antimicrobial activity of 3200 AU/mL for the first three and of 12800 AU/mL for P. pentosaceus 147 were obtained. Culture of P. pentosaceus 63 on modified MRS broth, showed the effect of some sources of carbon on the activity of bacteriocin, obtaining 12800 AU/mL with dextrose and 25600 AU/mL with maltose. Cultures of P. pentosaceus 145, 146 and 147 with these same sugars presented activity of 12800 AU/mL. It was observed that the modified MRS medium using whey increased the antimicrobial activity of the strains at 16000, 6400, 16000 and 19200 AU/mL for each strain respectively, keeping the biomass at values close to 9 log units. About nitrogen sources, it was observed that the combination of peptone (10 g /L), meat extract (10 g/L) and yeast extract (5 g/L) promoted the highest activity (12800 AU/mL), and in all cases MgSO4, MnSO4, K2HPO4 and ammonium citrate at low concentrations adversely affected bacteriocin production. Because P. pentosaceus 147 showed the highest antimicrobial activity in the presence of whey, it was used to evaluate the culture medium (peptone (10 g/L), meat extract (8 g/L), yeast extract (2 g/L), Tween® 80 (1 g/L), ammonium citrate (2 g/L), sodium acetate (5 g/L), MgSO4 (0.2 g/L), MnSO4 (0.04 g/L)). With the designed medium added with whey, 9.34 log units of biomass concentration and 19200 AU/mL were achieved for P. pentosaceus 147. The above suggest that the new medium promotes the antimicrobial activity of P. pentosaceus 147 allowing the use of an economic medium using whey.

Keywords: antimicrobial activity, bacteriocins, pediococcus, whey

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4264 The Therapeutic Rise of Turmeric: From Spice to Medicine

Authors: Merzak Siham, Benguerine Zohra, Si Tayeb Fatima, Bouzian Chaimaa Affaf, Jou Siham, Belkessam Nafissa

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Introduction: Medicinal plants, particularly spices, are essential for pharmacological research due to their health benefits. This study focuses on Curcuma longa, a spice recognized for its therapeutic properties. Materials and Methods: This study is based on a thorough search conducted on Google Scholar, PubMed, and ScienceDirect. From an initial selection of 25 articles, five were chosen to extract relevant information on Curcuma longa. Results and Discussions: Clinical studies have indicated that curcumin is well tolerated at doses up to 12 g/day. Its anti-rheumatic efficacy was compared to phenylbutazone in 18 individuals. Each participant received a daily dose of either 1200 mg of curcumin or 300 mg of phenylbutazone for 2 weeks. Curcumin was well tolerated at this dose and demonstrated activity comparable to phenylbutazone. Additionally, a study on 62 patients showed that curcumin sustainably relieved symptoms without toxicity. Its effects included reduced itching, lesions, and pain. In ten volunteers, administering 500 mg of curcumin for seven days resulted in a 33% decrease in lipid peroxidation, a 29% increase in HDL cholesterol, and a 12% decrease in total cholesterol. It is important to note that curcumin is a potent, selective inhibitor of phosphorylase kinase, an increased marker in psoriasis. Conclusion: Curcumin is promising as a future drug for various diseases, but its bioavailability must be improved through techniques such as nano encapsulation. Additionally, exploring chemical derivatives of curcumin could lead to more potent and targeted molecules.

Keywords: turmeric, spice, medicinal plants, pharmacological activities.

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4263 Studying the Effect of Reducing Thermal Processing over the Bioactive Composition of Non-Centrifugal Cane Sugar: Towards Natural Products with High Therapeutic Value

Authors: Laura Rueda-Gensini, Jader Rodríguez, Juan C. Cruz, Carolina Munoz-Camargo

Abstract:

There is an emerging interest in botanicals and plant extracts for medicinal practices due to their widely reported health benefits. A large variety of phytochemicals found in plants have been correlated with antioxidant, immunomodulatory, and analgesic properties, which makes plant-derived products promising candidates for modulating the progression and treatment of numerous diseases. Non-centrifugal cane sugar (NCS), in particular, has been known for its high antioxidant and nutritional value, but composition-wise variability due to changing environmental and processing conditions have considerably limited its use in the nutraceutical and biomedical fields. This work is therefore aimed at assessing the effect of thermal exposure during NCS production over its bioactive composition and, in turn, its therapeutic value. Accordingly, two modified dehydration methods are proposed that employ: (i) vacuum-aided evaporation, which reduces the necessary temperatures to dehydrate the sample, and (ii) window refractance evaporation, which reduces thermal exposure time. The biochemical composition of NCS produced under these two methods was compared to traditionally-produced NCS by estimating their total polyphenolic and protein content with Folin-Ciocalteu and Bradford assays, as well as identifying the major phenolic compounds in each sample via HPLC-coupled mass spectrometry. Their antioxidant activities were also compared as measured by their scavenging potential of ABTS and DPPH radicals. Results show that the two modified production methods enhance polyphenolic and protein yield in resulting NCS samples when compared to traditional production methods. In particular, reducing employed temperatures with vacuum-aided evaporation demonstrated to be superior at preserving polyphenolic compounds, as evidenced both in the total and individual polyphenol concentrations. However, antioxidant activities were not significantly different between these. Although additional studies should be performed to determine if the observed compositional differences affect other therapeutic activities (e.g., anti-inflammatory, analgesic, and immunoprotective), these results suggest that reducing thermal exposure holds great promise for the production of natural products with enhanced nutritional value.

Keywords: non-centrifugal cane sugar, polyphenolic compounds, thermal processing, antioxidant activity

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4262 The Effectiveness of Using Functional Rehabilitation with Children of Cerebral Palsy

Authors: Bara Yousef

Abstract:

The development of independency and functional participation is an important therapeutic goal for many children with cerebral palsy,They was many therapeutic approach have been used for treatment those children like neurodevelopment treatment, balance training strengthening and stretching exercise. More recently, therapy for children with cerebral palsy has focused on achieving functional goals using task-oriented interventions and summer camping model, which focus on activities that relevant and meaningful to the child, to learn more efficient and effective motor skills. We explore the effectiveness of using functional rehabilitation comparing with regular rehabilitation among 40 Saudi children with cerebral palsy in pediatric unit at Sultan Bin Abdul Aziz Humanitarian City-Ksa ,where 20 children randomly assign in control group who received rehabilitation based on regular therapy approach and other 20 children assign on experiment group who received rehabilitation based on functional therapy approach with an average of 45min OT treatment and 45 min PT treatment- daily within a period of 6 week. Our finding reported that children in experiment group has improved in gross motor function with an average from 49.4 to 57.6 based on GMFM 66 as primary outcome measure and improved in WeeFIM with an average from 52 to 62 while children in control group has improved with an average from 48.4 to 53.7 in GMFM and from 53 to and 58 in WeeFIM. Consequently, there has been growing interest in determining the effects of functional training programs as promising approach for these children.

Keywords: Cerebral Palsy (CP), gross motor function measure (GMFM66), pediatric Functional Independent Measure (WeeFIM), rehabilitation, disability

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4261 Cognitive Behaviour Drama: Playful Method to Address Fears in Children on the Higher-End of the Autism Spectrum

Authors: H.Karnezi, K. Tierney

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Childhood fears that persist over time and interfere with the children’s normal functioning may have detrimental effects on their social and emotional development. Cognitive behavior therapy is considered highly effective in treating fears and anxieties. However, given that many childhood fears are based on fantasy, the applicability of CBT may be hindered by cognitive immaturity. Furthermore, a lack of motivation to engage in therapy is another commonly encountered obstacle. The purpose of this study was to introduce and evaluate a more developmentally appropriate intervention model, specifically designed to provide phobic children with the motivation to overcome their fears. To this end, principles and techniques from cognitive and behavior therapies are incorporated into the ‘Drama in Education’ model. The Cognitive Behaviour Drama (CBD) method involves using the phobic children’s creativity to involve them in the therapeutic process. The children are invited to engage in exciting fictional scenarios tailored around their strengths and special interests. Once their commitment to the drama is established, a problem that they will feel motivated to solve is introduced. To resolve it, the children will have to overcome a number of obstacles culminating in an in vivo confrontation with the fear stimulus. The study examined the application of the CBD model in three single cases. Results in all three cases shown complete elimination of all fear-related symptoms. Preliminary results justify further evaluation of the Cognitive Behaviour Drama model. It is time and cost-effective, ensuring the clients' immediate engagement in the therapeutic process.

Keywords: phobias, autism, intervention, drama

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4260 Innovative Preparation Techniques: Boosting Oral Bioavailability of Phenylbutyric Acid Through Choline Salt-Based API-Ionic Liquids and Therapeutic Deep Eutectic Systems

Authors: Lin Po-Hsi, Sheu Ming-Thau

Abstract:

Urea cycle disorders (UCD) are rare genetic metabolic disorders that compromise the body's urea cycle. Sodium phenylbutyrate (SPB) is a medication commonly administered in tablet or powder form to lower ammonia levels. Nonetheless, its high sodium content poses risks to sodium-sensitive UCD patients. This necessitates the creation of an alternative drug formulation to mitigate sodium load and optimize drug delivery for UCD patients. This study focused on crafting a novel oral drug formulation for UCD, leveraging choline bicarbonate and phenylbutyric acid. The active pharmaceutical ingredient-ionic liquids (API-ILs) and therapeutic deep eutectic systems (THEDES) were formed by combining these with choline chloride. These systems display characteristics like maintaining a liquid state at room temperature and exhibiting enhanced solubility. This in turn amplifies drug dissolution rate, permeability, and ultimately oral bioavailability. Incorporating choline-based phenylbutyric acid as a substitute for traditional SPB can effectively curtail the sodium load in UCD patients. Our in vitro dissolution experiments revealed that the ILs and DESs, synthesized using choline bicarbonate and choline chloride with phenylbutyric acid, surpassed commercial tablets in dissolution speed. Pharmacokinetic evaluations in SD rats indicated a notable uptick in the oral bioavailability of phenylbutyric acid, underscoring the efficacy of choline salt ILs in augmenting its bioavailability. Additional in vitro intestinal permeability tests on SD rats authenticated that the ILs, formulated with choline bicarbonate and phenylbutyric acid, demonstrate superior permeability compared to their sodium and acid counterparts. To conclude, choline salt ILs developed from choline bicarbonate and phenylbutyric acid present a promising avenue for UCD treatment, with the added benefit of reduced sodium load. They also hold merit in formulation engineering. The sustained-release capabilities of DESs position them favorably for drug delivery, while the low toxicity and cost-effectiveness of choline chloride signal potential in formulation engineering. Overall, this drug formulation heralds a prospective therapeutic avenue for UCD patients.

Keywords: phenylbutyric acid, sodium phenylbutyrate, choline salt, ionic liquids, deep eutectic systems, oral bioavailability

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4259 Sustainable Nanoengineering of Copper Oxide: Harnessing Its Antimicrobial and Anticancer Capabilities

Authors: Yemane Tadesse Gebreslassie, Fisseha Guesh Gebremeskel

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Nanotechnology has made remarkable advancements in recent years, revolutionizing various scientific fields, industries, and research institutions through the utilization of metal and metal oxide nanoparticles. Among these nanoparticles, copper oxide nanoparticles (CuO NPs) have garnered significant attention due to their versatile properties and wide-range applications, particularly, as effective antimicrobial and anticancer agents. CuO NPs can be synthesized using different methods, including physical, chemical, and biological approaches. However, conventional chemical and physical approaches are expensive, resource-intensive, and involve the use of hazardous chemicals, which can pose risks to human health and the environment. In contrast, biological synthesis provides a sustainable and cost-effective alternative by eliminating chemical pollutants and allowing for the production of CuO NPs of tailored sizes and shapes. This comprehensive review focused on the green synthesis of CuO NPs using various biological resources, such as plants, microorganisms, and other biological derivatives. Current knowledge and recent trends in green synthesis methods for CuO NPs are discussed, with a specific emphasis on their biomedical applications, particularly in combating cancer and microbial infections. This review highlights the significant potential of CuO NPs in addressing these diseases. By capitalizing on the advantages of biological synthesis, such as environmental safety and the ability to customize nanoparticle characteristics, CuO NPs have emerged as promising therapeutic agents for a wide range of conditions. This review presents compelling findings, demonstrating the remarkable achievements of biologically synthesized CuO NPs as therapeutic agents. Their unique properties and mechanisms enable effective combating against cancer cells and various harmful microbial infections. CuO NPs exhibit potent anticancer activity through diverse mechanisms, including induction of apoptosis, inhibition of angiogenesis, and modulation of signaling pathways. Additionally, their antimicrobial activity manifests through various mechanisms, such as disrupting microbial membranes, generating reactive oxygen species, and interfering with microbial enzymes. This review offers valuable insights into the substantial potential of biologically synthesized CuO NPs as an alternative approach for future therapeutic interventions against cancer and microbial infections.

Keywords: copper oxide nanoparticles, green synthesis, nanotechnology, microbial infection

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4258 Renegotiating the Filipino Bakla Culture: A Semiotic Analysis of Drag Performance in Eat Bulaga’s Kalye Serye

Authors: Ruepert Jiel Cao

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This study explores the renegotiation of bakla culture in Philippine media in the context of Kalye Serye segment of the popular Filipino noontime variety show Eat Bulaga. Although the term “bakla” is usually translated to “gay” or “homosexual male” in English, they do not mean the same. The western notion of a gay refers to a male person attracted to another male person but still retains the masculine physical attributes. However, the bakla embodies loudness, femininity, and transvestitism. Hence, a bakla is a gay man aspiring to be a woman by assuming feminine actions and appearance, a definition much closer to a transgender. The Philippine media usually employs the bakla culture in comedy programs. The bakla nowadays is usually associated with the people of lower economic strata and carries a pathological connotation. The Filipino television program Eat Bulaga, which has been airing for more than 36 years, is fond of using bakla in comedy. However, the recently launched segment entitled Kalye Serye (literally “Street [Television] Series”), while still employing drag performance to incorporate bakla culture in comedy, renegotiates the bakla culture by deviating from the stereotypical notion of bakla. In this study, this researcher asks: (1) How does Kalye Serye renegotiate the Filipino concept of bakla in terms of economic aspirations and social norms? (2) How does Kalye Serye reappropriate the bakla culture to fit non-comedic performances? The study examines 15 purposively selected Kalye Serye episodes. Seven were selected from the Thursday episodes, seven from Saturday episodes, and the Lenten special episode. These were selected to cover as many characters and different character roles as possible. Data was constructed by identifying and coding the roles, physical appearance and gestures, and key dialogs of the characters. A total of six female characters played by three different male actors were examined. Semiotic analysis using semiotics of Roland Barthes was performed to produce a reading of the characters. Findings show that through physical appearance, the characters associate bakla with the economic affluence through the use of expensive-looking clothes, jewelries, cars, and elaborate gestures. This represents a new economic but old western aspiration of the bakla. In terms of social norms, the characters try to revive the traditional concepts of femininity, courtship, and respect, values which are touted to be lost in the current generation of Filipinos. This is quite ironic because while there is a seemingly tolerant attitude towards all forms of queerness, the bakla is considered immoral and yet, the bakla is used to teach about morality and values. Finally, the characters break the traditional association of the bakla with slapstick comedy and their roles are reappropriated to suit dramatic roles. By refraining from portraying the bakla in ridiculous manner (physically and in terms of roles), the bakla lends itself well in the performance of dramatic roles and their ridiculous and pathological associations removed. Future research may include other Filipino or Asian portrayals of queerness to get a better understanding of how queerness is incorporated in contemporary popular culture.

Keywords: bakla, drag performance, popular culture, queer representation

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4257 Prevailing Clinical Evidence on Medicinal Hemp (Cannabis Sativa L.)

Authors: Siti Hajar Muhamad Rosli, Xin Yi Lim, Terence Yew Chin Tan, Muhammad nor Farhan Sa’At, Syazwani Sirdar Ali, Ami Fazlin Syed Mohamed

Abstract:

A growing interest on therapeutic benefits of hemp (Cannabis sativa subsp. sativa) is evident in the pharmaceutical market, attributed to its lower levels of psychoactive constituent delta-9-tetrahydronannabidiol (THC). Deemed as a legal and safer alternative to its counterpart marijuana, the use of medicinal hemp is highly debatable as current scientific evidence on the efficacy for clinical use is yet to be established This study was aimed to provide an overview of the current landscape of hemp research, through recent clinical findings specific to the pharmacological properties of the hemp plant and its derived compounds. A systematic search was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis-ScR (PRISMA) checklist on electronic databases (MEDLINE, OVID, Cochrane Library Central, and Clinicaltrials.gov) for articles published from 2009 to 2019. With predetermined inclusion criteria, all human trials with hemp intervention were included. A total of 18 human trials were identified, investigating therapeutic effects on the neuronal, gastrointestinal, musculoskeletal and immune system, with sample sizes ranging from one to 194 subjects. Three randomised controlled trials showed hempseed pills (in Traditional Chinese Medicine formulation MaZiRenWan) consumption significantly improved spontaneous bowel movement in functional constipation. The use of commercial cannabidiol (CBD) sourced from hemp suggested benefits in cannabis dependence, epilepsy, and anxiety disorders. However, there was insufficient evidence to suggest analgesic or anxiolytics effects of hemp being equivalent to marijuana. All clinical trials reviewed varied in terms of test item formulation and standardisation, which made it challenging to confirm overall efficacy for a specific disease or condition. Published efficacy data on hemp are still at a preliminary level, with limited high quality clinical evidence for any specific therapeutic indication. With multiple variants of this plant having different phytochemical and bioactive compounds, future empirical research should focus on uniformity in experimental designs to further strengthen the notion of using medicinal hemp.

Keywords: cannabis, complementary medicine, hemp, herbal medicine.

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4256 ‘Only Amharic or Leave Quick!’: Linguistic Genocide in the Western Tigray Region of Ethiopia

Authors: Merih Welay Welesilassie

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Language is a potent instrument that does not only serve the purpose of communication but also plays a pivotal role in shaping our cultural practices and identities. The right to choose one's language is a fundamental human right that helps to safeguard the integrity of both personal and communal identities. Language holds immense significance in Ethiopia, a nation with a diverse linguistic landscape that extends beyond mere communication to delineate administrative boundaries. Consequently, depriving Ethiopians of their linguistic rights represents a multifaceted punishment, more complex than food embargoes. In the aftermath of the civil war that shook Ethiopia in November 2020, displacing millions and resulting in the loss of hundreds of thousands of lives, concerns have been raised about the preservation of the indigenous Tigrayan language and culture. This is particularly true following the annexation of western Tigray into the Amhara region and the implementation of an Amharic-only language and culture education policy. This scholarly inquiry explores the intricacies surrounding the Amhara regional state's prohibition of Tigrayans' indigenous language and culture and the subsequent adoption of a monolingual and monocultural Amhara language and culture in western Tigray. The study adopts the linguistic genocide conceptual framework as an analytical tool to gain a deeper insight into the factors that contributed to and facilitated this significant linguistic and cultural shift. The research was conducted by interviewing ten teachers selected through a snowball sampling. Additionally, document analysis was performed to support the findings. The findings revealed that the push for linguistic and cultural assimilation was driven by various political and economic factors and the desire to promote a single language and culture policy. This process, often referred to as ‘Amharanization,’ aimed to homogenize the culture and language of the society. The Amhara authorities have enacted several measures in pursuit of their objectives, including the outlawing of the Tigrigna language, punishment for speaking Tigrigna, imposition of the Amhara language and culture, mandatory relocation, and even committing heinous acts that have inflicted immense physical and emotional suffering upon members of the Tigrayan community. Upon conducting a comprehensive analysis of the contextual factors, actions, intentions, and consequences, it has been posited that there may be instances of linguistic genocide taking place in the Western Tigray region. The present study sheds light on the severe consequences that could arise because of implementing monolingual and monocultural policies in multilingual areas. Through thoroughly scrutinizing the implications of such policies, this study provides insightful recommendations and directions for future research in this critical area.

Keywords: linguistic genocide, linguistic human right, mother tongue, Western Tigray

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4255 Study on the Overseas Dissemination and Acceptance of the English Translation of YU Hua’s to Live

Authors: Luo Xi

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Taking the English translation of Yu Hua's To Live as an example, this paper makes a quantitative description and qualitative analysis of its overseas dissemination and acceptance from the perspective of the actual audience -- readers. It is found that the English translation of To Live has been widely disseminated and accepted overseas. The book has been well received overseas. With the English version of To Live, overseas readers have an in-depth understanding of Chinese history, politics, and culture. At the same time, the work shows the admirable qualities of Chinese people. It also conveys the core human values. And thus, overseas readers have gained a deeper understanding of life and are spiritually inspired. From the perspective of readers, this paper studies the successful overseas dissemination of the English translation of Yu Hua's To Live to provide a reference for the further overseas dissemination of Chinese culture.

Keywords: to live, english translation, overseas dissemination and acceptance, readers’ comments

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4254 Inf-γ and Il-2 Asses the Therapeutic Response in Anti-tuberculosis Patients at Jamot Hospital Yaounde, Cameroon

Authors: Alexandra Emmanuelle Membangbi, Jacky Njiki Bikoï, Esther Del-florence Moni Ndedi, Marie Joseph Nkodo Mindimi, Donatien Serge Mbaga, Elsa Nguiffo Makue, André Chris Mikangue Mbongue, Martha Mesembe, George Ikomey Mondinde, Eric Walter Perfura-yone, Sara Honorine Riwom Essama

Abstract:

Background: Tuberculosis (TB) is one of the top lethal infectious diseases worldwide. In recent years, interferon-γ (INF-γ) release assays (IGRAs) have been established as routine tests for diagnosing TB infection. However, produced INF-γ assessment failed to distinguish active TB (ATB) from latent TB infection (LTBI), especially in TB epidemic areas. In addition to IFN-γ, interleukin-2 (IL-2), another cytokine secreted by activated T cells, is also involved in immune response against Mycobacterium tuberculosis. The aim of the study was to assess the capacity of IFN-γ and IL2 to evaluate the therapeutic response of patients on anti-tuberculosis treatment. Material and Methods: We conducted a cross-sectional study in the Pneumonology Departments of the Jamot Hospital in Yaoundé between May and August 2021. After signed the informed consent, the sociodemographic data, as well as 5 mL of blood, were collected in the crook of the elbow of each participant. Sixty-one subjects were selected (n= 61) and divided into 4 groups as followed: group 1: resistant tuberculosis (n=13), group 2: active tuberculosis (n=19), group 3 cured tuberculosis (n=16), and group 4: presumed healthy persons (n=13). The cytokines of interest were determined using an indirect Enzyme-linked Immuno-Sorbent Assay (ELISA) according to the manufacturer's recommendations. P-values < 0.05 were interpreted as statistically significant. All statistical calculations were performed using SPSS version 22.0 Results: The results showed that men were more 14/61 infected (31,8%) with a high presence in active and resistant TB groups. The mean age was 41.3±13.1 years with a 95% CI = [38.2-44.7], the age group with the highest infection rate was ranged between 31 and 40 years. The IL-2 and INF-γ means were respectively 327.6±160.6 pg/mL and 26.6±13.0 pg/mL in active tuberculosis patients, 251.1±30.9 pg/mL and 21.4±9.2 pg/mL in patients with resistant tuberculosis, while it was 149.3±93.3 pg/mL and 17.9±9.4 pg/mL in cured patients, 15.1±8.4 pg/mL and 5.3±2.6 pg/mL in participants presumed healthy (p <0.0001). Significant differences in IFN-γ and IL-2 rates were observed between the different groups. Conclusion: Monitoring the serum levels of INF-γ and IL-2 would be useful to evaluate the therapeutic response of anti-tuberculosis patients, particularly in the both cytokines association case, that could improve the accuracy of routine examinations.

Keywords: antibiotic therapy, interferon gamma, interleukin 2, tuberculosis

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4253 Kanga Traditional Costume as a Tool for Community Empowerment in Tanzania in Ubuntu perspective - A Literature Review

Authors: Meinrad Haule Lembuka

Abstract:

Introduction: Ubuntu culture represents African humanism with collective and positive feeling of people living together, interdependence, equally and peaceful etc. Overtime, Ubuntu culture developed varieties of communicative strategies to express experiences, feelings and knowledge. Khanga or kanga (garment) is among the Ubuntu cultural practice of Bantu speaking people along the East African coast following interaction with Arabs and Bantu speaking people to formulate Swahili culture. Kanga or Kanga is a Swahili word which means a traditional soft cotton cloths in varieties of colours, patterns, and styles which as a deep cultural, historical, and social significance not only in Tanzania but the rest of East African coast. Swahili culture is a sub culture of Ubuntu African culture which is rich in customs and rituals that serve to preserve goodness and life where Tanzania, like the rest of East African societies along the Indian coast engaged in kanga dressing custom under Swahili culture to express their feelings and knowledge sharing. After the independence of Tanzania (formerly Tanganyika) from British colonial rule, Kanga traditional dressing gained momentum in Swahili culture and spread to the rest of East Africa and beyond. To date kanga dressing holds a good position as a formal and informal tool for advocating marginalised groups, counselling, psychosocial therapy, liberation, compassion, love, justice, campaign, and cerebration etc. Methodology: A literature review method was guided by Ubuntu theory to assess the implications of kanga traditional dressing in empowering Tanzanian community. Findings: During slavery, slaves wore Kaniki and people despised Kaniki dressing due to its association with slavery. Ex-slave women seeking to become part of the Swahili society began to decorate their Kaniki clothes. After slavery was abolished in 1897, Kangas began to be used for self-empowerment and to indicate that the wearer had personal wealth. During colonial era, freedom of expressions for Africans were restricted by colonial masters thus Tanzanians used kanga to express the evils of colonialism and other social problems, Under Ubuntu value of unity and solidarity liberation and independence fighters crafted motto and liberation messages that were shared and spread rapidly in the community. Political parities like TANU used kanga to spread nationalism and Ujamaa policy. kanga is more than a piece of fabric-it is a space for women to voice unspeakable communication and a women-centred repository for indigenous knowledge, feminisms addressing social ills, happiness, campaigns, memories and reconciliation etc. Kanga provides an indirect voice and support vulnerable and marginalised populations and strongly it has proved to be a peaceful platform of capture attention of government and societies. Kanga textiles gained increased international fame when an Obama kanga design was produced upon the president’s election in 2008 and his visit to Tanzania in 2013. Conclusion: Kanga preserves and symbolises Swahili culture and contributes in realization of social justice, inclusion, national identity and unity. As an inclusive cultural tool, Kanga spread across Africa to international community and the practice has moved from being a woman domination dressing code to other sex orientations.

Keywords: African culture, Kanga, khanga, swahili culture, ubuntu

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4252 Chinese Travelers’ Outbound Intentions to Visit Short-and-Long Haul Destinations: The Impact of Cultural Distance

Authors: Lei Qin

Abstract:

Culture has long been recognized as a possible reason to influence travelers’ decisions, which explains why travelers in different countries make distinct decisions. Cultural distance is a concept illustrating how much difference there is between travelers’ home culture and that of the destination, but the research in distinguishing short-and-long haul travel destinations is limited. This study explored the research gap by examining the impact of cultural distance on Chinese travelers’ intentions to visit short-haul and long-haul destinations, respectively. Six cultural distance measurements, including five measurements calculated from secondary database (Kogut & Singh, Developed Kogut & Singh, Euclidean distance Index (EDI), world value survey index (WVS), social axioms measurement (SAM)) and perceived cultural distance (PCD) collected from the primary survey. Of the six measurements, culture distance has the opposite impact on Chinese outbound travelers’ intentions in the short-haul and long haul. For short-haul travel, travelers’ intentions for traveling can be positive influenced by cultural distance; a possible reason is that travelers’ novelty-seeking satisfaction is greater than the strangeness obtained from overseas regions. For long-haul travel, travelers’ intentions for traveling can be negative influenced by cultural distance, a possible explanation is that travelers’ uncertainty, risk, and language concerns of farther destinations.

Keywords: cultural distance, intention, outbound travel, short-long haul

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4251 The Complementary Explanations of Institutional and Feminist Perspectives for Female Social Enterprise in Pakistan

Authors: Mohammad Sohail Yunis, Hina Hashim, Alistair R. Anderson

Abstract:

Entrepreneurship is gendered with masculine qualities, yet social enterprise epitomizes caring a feminine quality. However enterprising practices may have little to do with gender. Consequently, the purpose of this paper is to examine practices using two very different explanatory theories, feminist and institutional theory, to establish the role played by gender. This study is situated in KP, the poor but traditional north of Pakistan. Utilising on an interpretive qualitative research approach, this research collected data through in-depth interviews with ten women social entrepreneurs of KP, Pakistan and analyzed using thematic analysis. Empirically, this paper identifies and describes on a number of interesting themes that relate to the women entrepreneurship such as 'women empowerment, patriarchal culture, role of culture and societal norms, religious extremism and terrorism, forced entrepreneurs, change creators, institutional corruption, and security issues'. In addition, female social enterprise in KP is set in a patriarchal, masculine culture, but the practices negotiate institutional obstacles to bring benefits to the disenfranchised. Finally, this research claims to present an original insight into female social entrepreneurship in a developing country context and provide fresh theoretical and empirical perspectives to advance knowledge and scholarship.

Keywords: female social entrepreneurship, institutional theory, feminist theory, developing countries

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4250 The Design of Smart Tactile Textiles for Therapeutic Applications

Authors: Karen Hong

Abstract:

Smart tactile textiles are a series of textile-based products that incorporates smart embedded technology to be utilized as tactile therapeutic applications for 2 main groups of target users. The first group of users will be children with sensory processing disorder who are suffering from tactile sensory dysfunction. Children with tactile sensory issues may have difficulty tolerating the sensations generated from the touch of certain textures on the fabrics. A series of smart tactile textiles, collectively known as ‘Tactile Toys’ are developed as tactile therapy play objects, exposing children to different types of touch sensations within textiles, enabling them to enjoy tactile experiences together with interactive play which will help them to overcome fear of certain touch sensations. The second group of users will be the elderly or geriatric patients who are suffering from deteriorating sense of touch. One of the common consequences of aging is suffering from deteriorating sense of touch and a decline in motoric function. With the focus in stimulating the sense of touch for this particular group of end users, another series of smart tactile textiles, collectively known as ‘Tactile Aids’ are developed also as tactile therapy. This range of products can help to maintain touch sensitivity and at the same time allowing the elderly to enjoy interactive play to practice their hand-eye coordination and enhancing their motor skills. These smart tactile textile products are being designed and tested out by the end users and have proofed their efficacy as tactile therapy enabling the users to lead a better quality of life.

Keywords: smart textiles, embedded technology, tactile therapy, tactile aids, tactile toys

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4249 Study of Therapeutic Potential of Dodonaea Viscosa Against Rheumatoid Arthritis in Collagen Induced Arthritic Mouse Model

Authors: Peter John, Zainab Ali, Attya Bhatti

Abstract:

Rheumatoid Arthritis (RA) is a systemic autoimmune inflammatory disease that primarily affects the joints. RA is caused in many cases by the interaction between genes and environmental factors, including tobacco, that primarily involves synovial joints. It typically starts in small peripheral joints, is usually symmetric, and progresses to involve proximal joints if left untreated. The prevalence of rheumatoid arthritis varies substantially around the globe, ranging from 0·25% to 1%.3. Rheumatoid arthritis can affect individuals of any age, with an increased incidence in people older than 40 years. Women are affected two to three times more frequently than men. The present work involved evaluating the toxicity and therapeutic potential of Dodonaea viscosa in a collagen-induced arthritic mouse model. Chemical analysis exhibited that Dodonaea viscosa has high levels of beneficial compounds, including phenols, flavonoids, and other phytochemicals. The Dodonaea viscosa showed significant antioxidant, anti-inflammatory, and anti-arthritic potential without toxic effects. Arthritic mice treated with Dodonaea viscosa showed reduced levels of rheumatoid factor and paw edema, while no significant effects on spleen indices and radiological examination of paws were found compared to control untreated arthritic mice. In summary, the Dodonaea viscosa treatment results in improvement in Arthritic Mice Model for which further studies are required.

Keywords: rheumatoid arthritis, dodonaea viscisa, anti-inflammatory, anti-rheumatic

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4248 Removal of Protein from Chromium Tanning Bath by Biological Treatment Using Pseudomonas sp.

Authors: Amel Benhadji, Mourad Taleb Ahmed, Rachida Maachi

Abstract:

The challenge for the new millennium is to develop an industrial system that has minimal socio-ecological impacts, without compromising quality of life. Leather industry is one of these industries demanding environmentally friendly products. In this study, we investigated the possibility of applying innovative low cost biological treatment using Pseudomonas aeruginosa. This strain tested the efficiency of the batch biological treatment in the recovery of protein and hexavalent chromium from chromium tanning bath. We have compared suspended and fixed bacteria culture. The results showed the removal of the total protein of treatment and a decrease of hexavalent chromium concentration is during the treatment. The better efficiency of the biological treatment is obtained when using fixed culture of P. aeruginosa.

Keywords: tanning wastewater, biological treatment, protein removal, hexavalent chromium

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4247 Green and Cost-Effective Biofabrication of Copper Oxide Nanoparticles: Exploring Antimicrobial and Anticancer Applications

Authors: Yemane Tadesse Gebreslassie, Fisseha Guesh Gebremeskel

Abstract:

Nanotechnology has made remarkable advancements in recent years, revolutionizing various scientific fields, industries, and research institutions through the utilization of metal and metal oxide nanoparticles. Among these nanoparticles, copper oxide nanoparticles (CuO NPs) have garnered significant attention due to their versatile properties and wide-range applications, particularly, as effective antimicrobial and anticancer agents. CuO NPs can be synthesized using different methods, including physical, chemical, and biological approaches. However, conventional chemical and physical approaches are expensive, resource-intensive, and involve the use of hazardous chemicals, which can pose risks to human health and the environment. In contrast, biological synthesis provides a sustainable and cost-effective alternative by eliminating chemical pollutants and allowing for the production of CuO NPs of tailored sizes and shapes. This comprehensive review focused on the green synthesis of CuO NPs using various biological resources, such as plants, microorganisms, and other biological derivatives. Current knowledge and recent trends in green synthesis methods for CuO NPs are discussed, with a specific emphasis on their biomedical applications, particularly in combating cancer and microbial infections. This review highlights the significant potential of CuO NPs in addressing these diseases. By capitalizing on the advantages of biological synthesis, such as environmental safety and the ability to customize nanoparticle characteristics, CuO NPs have emerged as promising therapeutic agents for a wide range of conditions. This review presents compelling findings, demonstrating the remarkable achievements of biologically synthesized CuO NPs as therapeutic agents. Their unique properties and mechanisms enable effective combating against cancer cells and various harmful microbial infections. CuO NPs exhibit potent anticancer activity through diverse mechanisms, including induction of apoptosis, inhibition of angiogenesis, and modulation of signaling pathways. Additionally, their antimicrobial activity manifests through various mechanisms, such as disrupting microbial membranes, generating reactive oxygen species, and interfering with microbial enzymes. This review offers valuable insights into the substantial potential of biologically synthesized CuO NPs as an alternative approach for future therapeutic interventions against cancer and microbial infections.

Keywords: biological synthesis, copper oxide nanoparticles, microbial infection, nanotechnology

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4246 Casteism in United Punjab: A Socio-Cultural Perspective

Authors: Zahoor Ahmad

Abstract:

Casteism has played a pivotal role in the social setup and political manipulations in Punjab. This tradition dates back to pre-British history. A number of scholars produced valuable work attributing the caste prejudice and division among the local communities. As a matter of fact, the history of Punjab witnessed a tangible economic, Muslim-non-Muslim, hatred culture towards low-profile castes & professions, and so on. It is obvious that caste ridden system already existed in Punjab before the advent of the British, who tremendously supported the same, and this division evidently affected every aspect of the political as well as social life of the region. This article highlights the characteristics of different castes and the contemptuous behavior of the low castes & professions in the area further, how the caste system influenced the local people and their culture.

Keywords: casteism, caste prejudice, division, Punjab

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4245 Art and Culture in the Development Period to Modernization in the Reign of King Rama VI

Authors: Weena Eiamprapai

Abstract:

The growth of Thai society in western style in the middle of Rattanakosin period can be defined as modernization /civilization. These terms had an influence on the development of the country in the reign of King Rama V owing to the governance reform, and cultures influenced by the West. Those were passed on until the reign of King Rama VI. The preference was not only for the renovation of architecture and arts based on Thai customs reflecting the prosperity and beauty of handicrafts but also for the acceptance of westernization. The remain of this acceptance includes the concept of such value as gentlemanly behavior like that in Victorian Era of the United Kingdom, and the support of women’s status. Moreover, the wide spread of modernization leads to the movement to change the country’s governance system from absolute monarchy to democracy by a group of people called Rattanakosin Era (R.E.) 130 party.

Keywords: art, culture, development period, modernization, King Rama VI

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4244 Narrating Irish Identity: Retrieving ‘Irishness’ in the Works of William Butler Yeats and Seamus Heaney

Authors: Rafik Massoudi

Abstract:

Irish identity continues to be discussed in various fields including social science, culture, literary humanities as well as political debates. In this context, Irishness had been usurped for a long time by the hegemonic power of the British Empire. That is why, Irish writers, in general, and Seamus Heaney along with William Butler Yeats, in particular, endeavored to retrieve this lost identity by shedding light on Irish history, folklore, communal traditions, landscape, indigenous people, language as well as culture. In this context, we may speak of a decolonizing attempt that allowed these writers to represent the autonomous Irish subjectivity by establishing an ethical relationship based on an extraordinary approach to the represented alterity. This article, indeed, places itself within the arena of postmodern, postcolonial discussions of the issue of identity and, particularly, of Irishness.

Keywords: identity, Irishess, narration, postcolonialism

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4243 Shear Stress and Oxygen Concentration Manipulation in a Micropillars Microfluidic Bioreactor

Authors: Deybith Venegas-Rojas, Jens Budde, Dominik Nörz, Manfred Jücker, Hoc Khiem Trieu

Abstract:

Microfluidics is a promising approach for biomedicine cell culture experiments with microfluidic bioreactors (MBR), which can provide high precision in volume and time control over mass transport and microenvironments in small-scale studies. Nevertheless, shear stress and oxygen concentration are important factors that affect the microenvironment and then the cell culture. It is presented a novel MBR design in which differences in geometry, shear stress, and oxygen concentration were studied and optimized for cell culture. The aim is to mimic the in vivo condition with biocompatible materials and continuous perfusion of nutrients, a healthy shear stress, and oxygen concentration. The design consists of a capture system of PDMS micropillars which keep cells in place, so it is not necessary any hydrogel or complicated scaffolds for cells immobilization. Besides, the design allows continuous supply with nutrients or even any other chemical for cell experimentation. Finite element method simulations were used to study and optimize the effect of parameters such as flow rate, shear stress, oxygen concentration, micropillars shape, and dimensions. The micropillars device was fabricated with microsystem technology such as soft-lithography, deep reactive ion etching, self-assembled monolayer, replica molding, and oxygen plasma bonding. Eight different geometries were fabricated and tested, with different flow rates according to the simulations. During the experiments, it was observed the effect of micropillars size, shape, and configuration for stability and shear stress control when increasing flow rate. The device was tested with several successful HepG2 3D cell cultures. With this MBR, the aforementioned parameters can be controlled in order to keep a healthy microenvironment according to specific necessities of different cell types, with no need of hydrogels and can be used for a wide range of experiments with cells.

Keywords: cell culture, micro-bioreactor, microfluidics, micropillars, oxygen concentration, shear stress

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4242 The Diagnostic Utility and Sensitivity of the Xpert® MTB/RIF Assay in Diagnosing Mycobacterium tuberculosis in Bone Marrow Aspirate Specimens

Authors: Nadhiya N. Subramony, Jenifer Vaughan, Lesley E. Scott

Abstract:

In South Africa, the World Health Organisation estimated 454000 new cases of Mycobacterium tuberculosis (M.tb) infection (MTB) in 2015. Disseminated tuberculosis arises from the haematogenous spread and seeding of the bacilli in extrapulmonary sites. The gold standard for the detection of MTB in bone marrow is TB culture which has an average turnaround time of 6 weeks. Histological examinations of trephine biopsies to diagnose MTB also have a time delay owing mainly to the 5-7 day processing period prior to microscopic examination. Adding to the diagnostic delay is the non-specific nature of granulomatous inflammation which is the hallmark of MTB involvement of the bone marrow. A Ziehl-Neelson stain (which highlights acid-fast bacilli) is therefore mandatory to confirm the diagnosis but can take up to 3 days for processing and evaluation. Owing to this delay in diagnosis, many patients are lost to follow up or remain untreated whilst results are awaited, thus encouraging the spread of undiagnosed TB. The Xpert® MTB/RIF (Cepheid, Sunnyvale, CA) is the molecular test used in the South African national TB program as the initial diagnostic test for pulmonary TB. This study investigates the optimisation and performance of the Xpert® MTB/RIF on bone marrow aspirate specimens (BMA), a first since the introduction of the assay in the diagnosis of extrapulmonary TB. BMA received for immunophenotypic analysis as part of the investigation into disseminated MTB or in the evaluation of cytopenias in immunocompromised patients were used. Processing BMA on the Xpert® MTB/RIF was optimised to ensure bone marrow in EDTA and heparin did not inhibit the PCR reaction. Inactivated M.tb was spiked into the clinical bone marrow specimen and distilled water (as a control). A volume of 500mcl and an incubation time of 15 minutes with sample reagent were investigated as the processing protocol. A total of 135 BMA specimens had sufficient residual volume for Xpert® MTB/RIF testing however 22 specimens (16.3%) were not included in the final statistical analysis as an adequate trephine biopsy and/or TB culture was not available. Xpert® MTB/RIF testing was not affected by BMA material in the presence of heparin or EDTA, but the overall detection of MTB in BMA was low compared to histology and culture. Sensitivity of the Xpert® MTB/RIF compared to both histology and culture was 8.7% (95% confidence interval (CI): 1.07-28.04%) and sensitivity compared to histology only was 11.1% (95% CI: 1.38-34.7%). Specificity of the Xpert® MTB/RIF was 98.9% (95% CI: 93.9-99.7%). Although the Xpert® MTB/RIF generates a faster result than histology and TB culture and is less expensive than culture and drug susceptibility testing, the low sensitivity of the Xpert® MTB/RIF precludes its use for the diagnosis of MTB in bone marrow aspirate specimens and warrants alternative/additional testing to optimise the assay.

Keywords: bone marrow aspirate , extrapulmonary TB, low sensitivity, Xpert® MTB/RIF

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4241 Identification of Potential Small Molecule Regulators of PERK Kinase

Authors: Ireneusz Majsterek, Dariusz Pytel, J. Alan Diehl

Abstract:

PKR-like ER kinase (PERK) is serine/threonie endoplasmic reticulum (ER) transmembrane kinase activated during ER-stress. PERK can activate signaling pathways known as unfolded protein response (UPR). Attenuation of translation is mediated by PERK via phosphorylation of eukaryotic initiation factor 2α (eIF2α), which is necessary for translation initiation. PERK activation also directly contributes to activation of Nrf2 which regulates expression of anti-oxidant enzymes. An increased phosphorylation of eIF2α has been reported in Alzheimer disease (AD) patient hippocampus, indicating that PERK is activated in this disease. Recent data have revealed activation of PERK signaling in non-Hodgkins lymphomas. Results also revealed that loss of PERK limits mammary tumor cell growth in vitro and in vivo. Consistent with these observations, activation of UPR in vitro increases levels of the amyloid precursor protein (APP), the peptide from which beta-amyloid plaques (AB) fragments are derived. Finally, proteolytic processing of APP, including the cleavages that produce AB, largely occurs in the ER, and localization coincident with PERK activity. Thus, we expect that PERK-dependent signaling is critical for progression of many types of diseases (human cancer, neurodegenerative disease and other). Therefore, modulation of PERK activity may be a useful therapeutic target in the treatment of different diseases that fail to respond to traditional chemotherapeutic strategies, including Alzheimer’s disease. Our goal will be to developed therapeutic modalities targeting PERK activity.

Keywords: PERK kinase, small molecule inhibitor, neurodegenerative disease, Alzheimer’s disease

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