Search results for: therapeutic jurisprudence
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1459

Search results for: therapeutic jurisprudence

1249 Combating Islamophobia in Australia: An Analysis of Six Legal and Holistic Strategies to Help Address Discrimination towards Muslims

Authors: F. Zamani Ashni, P. Gerber

Abstract:

In today's religious and political climate, Muslims find themselves the focus of much attention, often in the form of discrimination and vilification. There is a widely held belief that Islam and terrorism are inextricably intertwined. An anti-Muslim narrative has been shaping policy around the world for some time now. This study, which focuses on the experience of Muslims in Australia, provides guidance on legislative and other steps that can be taken by Australia to help address Islamophobia. This study provides a doctrinal analysis of the state, territory, and federal anti-discrimination laws in Australia. Using principles of statutory interpretation along aside an analysis of relevant jurisprudence, this study concludes that Australian anti-discrimination laws are ill-equipped to address modern-day Islamophobia. The study also finds that laws alone are insufficient to combat Islamophobia, and a more holistic approach is required. Six strategies are identified, which can, in combination, help to successfully respond to Islamophobia. In addition to legislative initiatives, combating Islamophobia requires Australia to promote inclusive human rights education, fair media coverage, strong leadership, integration of the Islamic community, and comprehensive documentation of anti-Muslim attacks.

Keywords: Australia, discrimination, Islamophobia, Muslim

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1248 Novel Phenolic Biopolyether with Potential Therapeutic Effect

Authors: V.Barbakadze, L.Gogilashvili, L.Amiranashvili, M.Merlani, K.Mulkijanyan

Abstract:

The high-molecular fractions from the several species of two genera (Symphytum and Anchusa) of Boraginaceae family Symphytum asperum, S. caucasicum, S. officinale, and Anchusa italica were isolated. According to IR, 13C and 1H NMR, 2D heteronuclear 1H/13C HSQC spectral data and 1D NOE experiment, the main structural element of these preparations was found to be a regularly substituted polyoxyethylene, namely poly[3-(3,4-dihydroxyenyl)glyceric acid] (PDPGA) or poly[oxy-1-carboxy-2-(3,4-dihydroxyphenyl)ethylene]. Such caffeic acid-derived biopolymer to our knowledge has not been known and has been identified for the first time. This compound represents a new class of natural polyethers with a residue of 3-(3,4-dihydroxyphenyl)glyceric acid as the repeating unit. Most of the carboxylic groups of PDPGA from A. italica unlike the polymer of S. asperum, S. caucasicum, and S. officinale are methylated. The 2D DOSY experiment gave the similar diffusion coefficient for the methylated and non-methylated signals of A. italica PDPGA. Both sets of signals fell in the same horizontal. This would imply a similar molecular weight for methylated and non-methylated polymers. This was further evidenced by graphic representations of the intensity decay of the 1H signals of aromatic H-2″ and H-1 at δ 7.16 and 5.24 and that of the methoxy group at δ 3.85. These three signals essentially showed the same curve shape. According to results of in vitro and in vivo experiments PDPGA of S.asperum and S.caucasicum could be considered as potential anti-inflammatory, wound healing and anti-cancer therapeutic agent.

Keywords: caffeic acid-derived polyether, poly[3-(3, 4-dihydroxyphenyl)glyceric acid], poly[oxy-1-carboxy-2-(3, 4-dihydroxyphenyl)ethylene], symphytum, anchusa

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1247 Characterisation, Extraction of Secondary Metabolite from Perilla frutescens for Therapeutic Additives: A Phytogenic Approach

Authors: B. M. Vishal, Monamie Basu, Gopinath M., Rose Havilah Pulla

Abstract:

Though there are several methods of synthesizing silver nano particles, Green synthesis always has its own dignity. Ranging from the cost-effectiveness to the ease of synthesis, the process is simplified in the best possible way and is one of the most explored topics. This study of extracting secondary metabolites from Perilla frutescens and using them for therapeutic additives has its own significance. Unlike the other researches that have been done so far, this study aims to synthesize Silver nano particles from Perilla frutescens using three available forms of the plant: leaves, seed, and commercial leaf extract powder. Perilla frutescens, commonly known as 'Beefsteak Plant', is a perennial plant and belongs to the mint family. The plant has two varieties classed within itself. They are frutescens crispa and frutescens frutescens. The species, frutescens crispa (commonly known as 'Shisho' in Japanese), is generally used for edible purposes. Its leaves occur in two forms, varying on the colors. It is found in two different colors of red with purple streaks and green with crinkly pattern on it. This species is aromatic due to the presence of two major compounds: polyphenols and perillaldehyde. The red (purple streak) variety of this plant is due to the presence of a pigment, Perilla anthocyanin. The species, frutescens frutescens (commonly known as 'Egoma' in Japanese), is the main source for perilla oil. This species is also aromatic, but in this case, the major compound which gives the aroma is Perilla ketone or egoma ketone. Shisho grows short as compared with Wild Sesame and both produce seeds. The seeds of Wild Sesame are large and soft whereas that of Shisho is small and hard. The seeds have a large proportion of lipids, ranging about 38-45 percent. Excluding those, the seeds have a large quantity of Omega-3 fatty acids, linoleic acid, and an Omega-6 fatty acid. Other than these, Perilla leaf extract has gold and silver nano particles in it. The yield comparison in all the cases have been done, and the process’ optimal conditions were modified, keeping in mind the efficiencies. The characterization of secondary metabolites includes GC-MS and FTIR which can be used to identify the components of purpose that actually helps in synthesizing silver nano particles. The analysis of silver was done through a series of characterization tests that include XRD, UV-Vis, EDAX, and SEM. After the synthesis, for being used as therapeutic additives, the toxin analysis was done, and the results were tabulated. The synthesis of silver nano particles was done in a series of multiple cycles of extraction from leaves, seeds and commercially purchased leaf extract. The yield and efficiency comparison were done to bring out the best and the cheapest possible way of synthesizing silver nano particles using Perilla frutescens. The synthesized nano particles can be used in therapeutic drugs, which has a wide range of application from burn treatment to cancer treatment. This will, in turn, replace the traditional processes of synthesizing nano particles, as this method will prove effective in terms of cost and the environmental implications.

Keywords: nanoparticles, green synthesis, Perilla frutescens, characterisation, toxin analysis

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1246 12-Week Comparative Clinical Trial with Low Dose Phentermine/Topiramate with Liraglutide on Obesity in Korea

Authors: Kyu Rae Lee

Abstract:

The aim of the study is to investigate the clinical efficacy of combination therapeutic modalities using liraglutide (1.2mg/d) add on low-dose phentermine (7.5 mg/d)/topiramate (50mg/d) medication on the obese patient in the bariatric clinic. We assessed the retrospective cohort clinical analyses to the clinical efficacy of medication and combination in the patients who visited the bariatric clinic. We measured all participants’ body fat (bioelectric impedance analysis), weight, height, and the cross-sectional areas of adipose tissues (umbilicus level) after keep fasting for 8 hours at 0, 4, 12 weeks. The design of the study was opened, paired t-test and Wilcoxon test were performed using SPSS for windows (ver.18, IL, USA) for comparison of weight, body fat, and adipose tissues. The participants were one hundred twenty-eight subjects aged 44.67 (1.18) years, 28.95 (0.39) kg/m², and female (82.7%). Their body fat was 40.57 (2.23%), and waist to hip ratio was 0.96 (0.01). The mean cross-sectional area of visceral adipose tissue was 142.59 (7.06) mm², and that of subcutaneous adipose was 274.37 (9.18) mm². 73 of them (57.5%) took medication only, 54 of them took medication with liraglutide for 12 weeks. The subjects in the medication group lost 5.4165 kg, 6.8069%, and those of the combination group did 6.2481 kg, 3.564%. The mean cross-sectional areas of visceral, subcutaneous adipose tissue in the medication group significantly decreased (p=.043), even more in the combination group. (p=.028). Further controlled clinical trials should be considered in the future. We conclude that the low dose of phentermine/topiramate with liraglutide therapeutic modalities would be more effective than phentermine/topiramate medication only in obesity treatment for 12 weeks.

Keywords: low dose phentermine, topiramate, liraglutide, obesity, efficacy

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1245 Noncovalent Antibody-Nanomaterial Conjugates: A Simple Approach to Produce Targeted Nanomedicines

Authors: Nicholas Fletcher, Zachary Houston, Yongmei Zhao, Christopher Howard, Kristofer Thurecht

Abstract:

One promising approach to enhance nanomedicine therapeutic efficacy is to include a targeting agent, such as an antibody, to increase accumulation at the tumor site. However, the application of such targeted nanomedicines remains limited, in part due to difficulties involved with biomolecule conjugation to synthetic nanomaterials. One approach recently developed to overcome this has been to engineer bispecific antibodies (BsAbs) with dual specificity, whereby one portion binds to methoxy polyethyleneglycol (mPEG) epitopes present on synthetic nanomedicines, while the other binds to molecular disease markers of interest. In this way, noncovalent complexes of nanomedicine core, comprising a hyperbranched polymer (HBP) of primarily mPEG, decorated with targeting ligands are able to be produced by simple mixing. Further work in this area has now demonstrated such complexes targeting the breast cancer marker epidermal growth factor receptor (EGFR) to show enhanced binding to tumor cells both in vitro and in vivo. Indeed the enhanced accumulation at the tumor site resulted in improved therapeutic outcomes compared to untargeted nanomedicines and free chemotherapeutics. The current work on these BsAb-HBP conjugates focuses on further probing antibody-nanomaterial interactions and demonstrating broad applicability to a range of cancer types. Herein are reported BsAb-HBP materials targeted towards prostate-specific membrane antigen (PSMA) and study of their behavior in vivo using ⁸⁹Zr positron emission tomography (PET) in a dual-tumor prostate cancer xenograft model. In this model mice bearing both PSMA+ and PSMA- tumors allow for PET imaging to discriminate between nonspecific and targeted uptake in tumors, and better quantify the increased accumulation following BsAb conjugation. Also examined is the potential for formation of these targeted complexes in situ following injection of individual components? The aim of this approach being to avoid undesirable clearance of proteinaceous complexes upon injection limiting available therapeutic. Ultimately these results demonstrate BsAb functionalized nanomaterials as a powerful and versatile approach for producing targeted nanomedicines for a variety of cancers.

Keywords: bioengineering, cancer, nanomedicine, polymer chemistry

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1244 Functionalized Single Walled Carbon Nanotubes: Targeting, Cellular Uptake, and Applications in Photodynamic Therapy

Authors: Prabhavathi Sundaram, Heidi Abrahamse

Abstract:

In recent years, nanotechnology coupled with photodynamic therapy (PDT) has received considerable attention in terms of improving the effectiveness of drug delivery in cancer therapeutics. The development of functionalized single-walled carbon nanotubes (SWCNTs) has become revolutionary in targeted photosensitizers delivery since it improves the therapeutic index of drugs. The objective of this study was to prepare, characterize and evaluate the potential of functionalized SWCNTs using hyaluronic acid and loading it with photosensitizer and to effectively target colon cancer cells. The single-walled carbon nanotubes were covalently functionalized with hyaluronic acid and the loaded photosensitizer by non-covalent interaction. The photodynamic effect of SWCNTs is detected under laser irradiation in vitro. The hyaluronic acid-functionalized nanocomposites had a good affinity with CD44 receptors, and it avidly binds on to the surface of CACO-2 cells. The cellular uptake of nanocomposites was studied using fluorescence microscopy using lyso tracker. The anticancer activity of nanocomposites was analyzed in CACO-2 cells using different studies such as cell morphology, cell apoptosis, and nuclear morphology. The combined effect of nanocomposites and PDT improved the therapeutic effect of cancer treatment. The study suggested that the nanocomposites and PDT have great potential in the treatment of colon cancer.

Keywords: colon cancer, hyaluronic acid, single walled carbon nanotubes, photosensitizers, photodynamic therapy

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1243 Counselor and Object of Hate: A Case Study of Latina Clinician and Two White Supremacist Patients

Authors: Reagan Rodriguez

Abstract:

The following research is a case study of two white patients with white extremist values and their Latina Clinician. Researchers suggest that white supremacy as an ideology has been documented in the United States since the early 1800s. Ethnicity and race were growing key factors linked to central motives behind hate crimes in U.S., which may suggest that we are living in another wave of white supremacist and domestic terrorism that seek to eradicate a threatening and dangerous “other”. This research seeks to address and contribute a qualitative perspective to white supremacist ideology within a bio-psycho-social framework. The current research seeks to contribute to address the gap in literature on ethnic minority clinicians and white patients with racist ideology. The research also seeks to examine the themes not commonly found in racially matched and gendered matched therapeutic dyads where patients hold white extremist values. This case study examines white supremacist ideology from a psychodynamic perspective, examining themes such as “feeling forgotten”, reduced empathy related to “broken promises”, sexualization of the passing minority counselor, and utilizing minimal autonomy in verbal and non-verbal signals. A thematic analysis of case notes and quotes are used to further contextualize emerging therapeutic themes and the psychodynamic analysis of the manifestation of white supremacist actions ranging from active to passive forms of violence.

Keywords: case study, extremism, race and gender, white supremacist ideology

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1242 Predictive Machine Learning Model for Assessing the Impact of Untreated Teeth Grinding on Gingival Recession and Jaw Pain

Authors: Joseph Salim

Abstract:

This paper proposes the development of a supervised machine learning system to predict the consequences of untreated bruxism (teeth grinding) on gingival (gum) recession and jaw pain (most often bilateral jaw pain with possible headaches and limited ability to open the mouth). As a general dentist in a multi-specialty practice, the author has encountered many patients suffering from these issues due to uncontrolled bruxism (teeth grinding) at night. The most effective treatment for managing this problem involves wearing a nightguard during sleep and receiving therapeutic Botox injections to relax the muscles (the masseter muscle) responsible for grinding. However, some patients choose to postpone these treatments, leading to potentially irreversible and costlier consequences in the future. The proposed machine learning model aims to track patients who forgo the recommended treatments and assess the percentage of individuals who will experience worsening jaw pain, gingival (gum) recession, or both within a 3-to-5-year timeframe. By accurately predicting these outcomes, the model seeks to motivate patients to address the root cause proactively, ultimately saving time and pain while improving quality of life and avoiding much costlier treatments such as full-mouth rehabilitation to help recover the loss of vertical dimension of occlusion due to shortened clinical crowns because of bruxism, gingival grafts, etc.

Keywords: artificial intelligence, machine learning, predictive insights, bruxism, teeth grinding, therapeutic botox, nightguard, gingival recession, gum recession, jaw pain

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1241 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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1240 Detection and Distribution Pattern of Prevelant Genotypes of Hepatitis C in a Tertiary Care Hospital of Western India

Authors: Upasana Bhumbla

Abstract:

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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1239 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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1238 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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1237 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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1236 Cognitive Behaviour Drama: Playful Method to Address Fears in Children on the Higher-End of the Autism Spectrum

Authors: H.Karnezi, K. Tierney

Abstract:

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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1235 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

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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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1234 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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1233 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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1232 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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1231 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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1230 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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1229 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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1228 Systematic Literature Review of Therapeutic Use of Autonomous Sensory Meridian Response (ASMR) and Short-Term ASMR Auditory Training Trial

Authors: Christine H. Cubelo

Abstract:

This study consists of 2-parts: a systematic review of current publications on the therapeutic use of autonomous sensory meridian response (ASMR) and a within-subjects auditory training trial using ASMR videos. The main intent is to explore ASMR as potentially therapeutically beneficial for those with atypical sensory processing. Many hearing-related disorders and mood or anxiety symptoms overlap with symptoms of sensory processing issues. For this reason, inclusion and exclusion criteria of the systematic review were generated in an effort to produce optimal search outcomes and avoid overly confined criteria that would limit yielded results. Criteria for inclusion in the review for Part 1 are (1) adult participants diagnosed with hearing loss or atypical sensory processing, (2) inclusion of measures related to ASMR as a treatment method, and (3) published between 2000 and 2022. A total of 1,088 publications were found in the preliminary search, and a total of 13 articles met the inclusion criteria. A total of 14 participants completed the trial and post-trial questionnaire. Of all responses, 64.29% agreed that the duration of auditory training sessions was reasonable. In addition, 71.43% agreed that the training improved their perception of music. Lastly, 64.29% agreed that the training improved their perception of a primary talker when there are other talkers or background noises present.

Keywords: autonomous sensory meridian response, auditory training, atypical sensory processing, hearing loss, hearing aids

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1227 New Vision of 'Social Europe': Renationalising the Integration Process in the Internal Market of the European Union

Authors: Robert Grzeszczak, Magdalena Gniadzik

Abstract:

The article deals with one of the most significant issues concerning the functioning of the internal market of the European Union – the free movement of workers and free movement of persons. The purpose is to identify the political and legal effects of the “renationalisation process” on the EU and its Member States. The concept of renationalisation is expressed through Member States’ aim to verify the relationship with the EU. The tendency is more visible in the public opinion of several MS’s of the ‘EU core’ and may be confirmed by the changes applied by the regulatory body. The thesis for the article is the return of renationalisation tendencies in the area of the Single Market, which is supported by, among others, an open criticism of the foundations of EU integration or considerations on withdrawal from the EU by some MS. This analysis will focus primarily on the effects that renationalisation may have on the free movement of persons. The free movement of persons is one of the key issues for the development of the European integration. It is still subject to theoretical reflections, new doubts and practical issues. The latest developments in politics, law and jurisprudence demonstrate the need to reflect on the attempts to redefine certain principles regarding migrant EU workers and their protection against nationality-based discrimination.

Keywords: European Union, Singel Market, free movement of persons, posting of workers

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1226 Exploring the Link between Hoarding Disorder and Trauma: A Scoping Review

Authors: Murray Anderson, Galina Freed, Karli Jahn

Abstract:

Trauma is increasingly recognized as an important construct that has health implications for those who struggle with various mental health issues. For those individuals who meet the criteria for a diagnosis of hoarding disorder (HD), many have experienced some form of trauma. Further, some of the therapeutic interventions for those with HD can further perpetuate or magnify the experience of trauma. Therefore, the aim of this scoping review is to identify and document the nature and extent of research evidence related to trauma as it connects with HD. This review was guided by the questions, ‘How can our understanding of the trauma cycle help us to better appreciate the experiences of individuals who hoard, and how will a trauma informed lens inform the interventions for hoarding disorder? A comprehensive literature search was performed to identify original studies that contained the words “hoarding” and “trauma.” PsychINFO”,''EBSCO host,” “CINAHL” and “PubMed” were searched between January 2005 and April 2021. Articles were screened by three reviewers. Data extracted included publication date, demographics, study design, type of analysis, and noted connections between hoarding and trauma. Of the 329 articles, all duplicates, articles on hoardings of animals, articles not in English, and those without full-text availability were removed. Five categories were found in the remaining 45 articles, including (a) traumatic and stressful life events; (b) the link between posttraumatic stress disorder, trauma, and hoarding; (c) the relationships between different comorbidities, trauma, and hoarding; (d) the lack of early emotional expression and other forms of parental deprivation; and (e) the role of attachment. Lastly, the literature explains how the links between hoarding and trauma are difficult to study due to the highly stigmatized identities with this population. The review provided strong support for the connections between the experience of trauma and HD. What is missing from the literature is the use of a trauma-informed lens to better account for the ways in which hoarding disorder is understood. Other missing pieces in the literature are the potential uses of a trauma-informed lens to enhance the therapeutic process, to understand and reduce treatment attrition, and to improve treatment outcomes. The application of a trauma informed lens could improve our understanding of effective interactions among clients, families, and communities and improve the education around hoarding-related matters. Exploring the connections between trauma and HD can improve therapeutic delivery and destigmatize the experience of dealing with clutter and hoarding concerns. This awareness can also provide health care professionals with both the language and skills to liberate them from a reductionist view on HD.

Keywords: hoarding, attachment, parental deprivation, trauma

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1225 Floating Oral in Situ Gelling System of Anticancer Drug

Authors: Umme Hani, Mohammed Rahmatulla, Mohammed Ghazwani, Ali Alqahtani, Yahya Alhamhoom

Abstract:

Background and introduction: Neratinib is a potent anticancer drug used for the treatment of breast cancer. It is poorly soluble at higher pH, which tends to minimize the therapeutic effects in the lower gastrointestinal tract (GIT) leading to poor bioavailability. An attempt has been made to prepare and develop a gastro-retentive system of Neratinib to improve the drug bioavailability in the GIT by enhancing the gastric retention time. Materials and methods: In the present study a three-factor at two-level (23) factorial design based optimization was used to inspect the effects of three independent variables (factors) such as sodium alginate (A), sodium bicarbonate (B) and sodium citrate (C) on the dependent variables like in vitro gelation, in vitro floating, water uptake and percentage drug release. Results: All the formulations showed pH in the range 6.7 ±0.25 to 7.4 ±0.24, percentage drug content was observed to be 96.3±0.27 to 99.5 ±0.28%, in vitro gelation observed as gelation immediate remains for an extended period. Percentage of water uptake was in the range between 9.01±0.15 to 31.01±0.25%, floating lag time was estimated form 7±0.39 to 57±0.36 sec. F4 and F5 showed floating even after 12hrs. All formulations showed a release of around 90% drug release within 12hr. It was observed that the selected independent variables affect the dependent variables. Conclusion: The developed system may be a promising and alternative approach to augment gastric retention of drugs and enhances the therapeutic efficacy of the drug.

Keywords: neratinib, 2³ factorial design, sodium alginate, floating, in situ gelling system

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1224 Strategies of Drug Discovery in Insects

Authors: Alaaeddeen M. Seufi

Abstract:

Many have been published on therapeutic derivatives from living organisms including insects. In addition to traditional maggot therapy, more than 900 therapeutic products were isolated from insects. Most people look at insects as enemies and others believe that insects are friends. Many beneficial insects rather than Honey Bees, Silk Worms and Shellac insect could insure human-insect friendship. In addition, insects could be MicroFactories, Biosensors or Bioreactors. InsectFarm is an amazing example of the applied research that transfers insects from laboratory to market by Prof Mircea Ciuhrii and co-workers. They worked for 18 years to derive therapeutics from insects. Their research resulted in production of more than 30 commercial medications derived from insects (e.g. Imunomax, Noblesse, etc.). Two general approaches were followed to discover drugs from living organisms. Some laboratories preferred biochemical approach to purify components of the innate immune system of insects and insect metabolites as well. Then the purified components could be tested for many therapeutic trials. Other researchers preferred molecular approach based on proteomic studies. Components of the innate immune system of insects were then tested for their medical activities. Our Laboratory team preferred to induce insect immune system (using oral, topical and injection routes of administration), then a transcriptomic study was done to discover the induced genes and to identify specific biomarkers that can help in drug discovery. Biomarkers play an important role in medicine and in drug discovery and development as well. Optimum biomarker development and application will require a team approach because of the multifaceted nature of biomarker selection, validation, and application. This team uses several techniques such as pharmacoepidemiology, pharmacogenomics, and functional proteomics; bioanalytical development and validation; modeling and simulation to improve and refine drug development. Our Achievements included the discovery of four components of the innate immune system of Spodoptera littoralis and Musca domestica. These components were designated as SpliDef (defesin), SpliLec (lectin), SpliCec (cecropin) and MdAtt (attacin). SpliDef, SpliLec and MdAtt were confirmed as antimicrobial peptides, while SpliCec was additionally confirmed as anticancer peptide. Our current research is going on to achieve something in antioxidants and anticoagulants from insects. Our perspective is to achieve something in the mass production of prototypes of our products and to reach it to the commercial level. These achievements are the integrated contributions of everybody in our team staff.

Keywords: AMPs, insect, innate immunitty, therappeutics

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1223 Comparative Study between Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on Ulcerative Colitis Induced Experimentally in Rats

Authors: Azza H. El-Medany, Hanan H. Hagar, Jamila H. El-Medany

Abstract:

Ulcerative colitis (UC) is one of chronic inflammatory diseases primarily affecting colon with unknown etiology. Some researches papers mentioned the possibility of the use of drugs that affect the angiotensin II in reducing the complication of ulcerative colitis. The aim of the present study is to evaluate the potential protective and therapeutic effects of captopril and valsartan on ulcerative colitis induced experimentally in rats using acetic acid. The results were assessed by histological assessment of colonic tissues and measurement of malondialdehyde (MDA), tumor necrosis factor (TNF-α), transforming growth factor (TGF-1B), angiotensin converting enzyme (ACE), reduced glutathione (GSH) and platelet activating factor (PAF) levels in colonic tissues. Oral pre-treatment with captopril or valsartan in a dose of 30 mgkg-1 body weight for 2 weeks before induction of colitis (prophylactic groups) and continuously for 2 weeks after induction (therapeutic groups) significantly reduce MDA, TNF-α, PAF, TGF-1B and ACE levels in colonic tissues as compared to acetic acid control group. Also, a significant increase in GSH level was observed in colonic tissues. Captopril and valsartan attenuated the macroscopic and microscopic colonic damage induced by acetic acid. These results suggest that either captopril or valsartan may be effective as prophylactic or treatment of UC through inhibition of ACE and scavenging effect on oxygen-derived free radicals.

Keywords: captopril, valsartan, angiotensin converting enzyme, reduced glutathione, tumor necrosis factor

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1222 A Systematic Review on Dietary Interventions for Iron Deficiency Anemia (IDA) in Under-Five Children in Nigeria

Authors: Justina Ijeoma Ezebuwa, Catherine C. Ikewuchi, Eka B. Essien, Francis C. Anacletus

Abstract:

Iron deficiency anemia (IDA) is a significant problem in Nigeria, especially in children under five. Intervention options for treating anemia in under-five children have also been the subject of research. This study aims to synthesize the evidence on dietary interventions for managing iron deficiency anemia in under-five children in Nigeria. This study uses a systematic review method to collect relevant studies to answer the research questions and a narrative synthesis to analyze and synthesize the findings of this study. Cochrane, PubMed, and ScienceDirect databases were thoroughly searched, and five (5) articles were selected for this study. The results show that dietary interventions, such as daily multi-nutrient fortified dairy-based drinks, biofortified (yellow/ white) cassava rich in pro-vitamin A, iron supplementation in foods, and ready-to-use therapeutic food (RUTF) may be relevant to the management of iron deficiency anemia in under-five children in Nigeria. The study also shows that daily multi-nutrient fortified dairy-based drinks may be more effective, feasible, and culturally acceptable for managing anemia in under-5 children in Nigeria. In addition, daily multi-nutrient fortified dairy-based drinks and ready-to-use therapeutic food (RUTF) were reported to have the potential to improve the growth, cognitive development, and overall health outcomes of under-five children with iron deficiency anemia in Nigeria. Recommendations for future studies in this research area and for public health practitioners and policymakers were provided.

Keywords: dietary intervention, iron deficiency anemia, under-five children, Nigeria

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1221 'Antibody Exception' under Dispute and Waning Usage: Potential Influence on Patenting Antibodies

Authors: Xiangjun Kong, Dongning Yao, Yuanjia Hu

Abstract:

Therapeutic antibodies have become the most valuable and successful class of biopharmaceutical drugs, with a huge market potential and therapeutic advantages. Antibody patents are, accordingly, extremely important. As the technological limitation of the early stage of this field, the U. S. Patent and Trademark Offices (USPTO) have issued guidelines that suggest an exception for patents claiming a genus of antibodies that bind to a novel antigen, even in the absence of any experimental antibody production. This 'antibody exception' allowed for a broad scope on antibody claims, and led a global trend to patent antibodies without antibodies. Disputes around the pertinent patentability and written description issues remain particularly intense. Yet the validity of such patents had not been overtly challenged until Centocor v. Abbott, which restricted the broad scope of antibody patents and hit the brakes on the 'antibody exception'. The courts tend to uphold the requirement for adequate description of antibodies in the patent specifications, to avoid overreaching antibody claims. Patents following the 'antibody exception' are at risk of being found invalid for inadequately describing what they have claimed. However, the relation between the court and USPTO guidelines remains obscure, and the waning of the 'antibody exception' has led to further disputes around antibody patents. This uncertainty clearly affects patent applications, antibody innovations, and even relevant business performance. This study will give an overview of the emergence, debate, and waning usage of the 'antibody exception' in a number of enlightening cases, attempting to understand the specific concerns and the potential influence of antibody patents. We will then provide some possible strategies for antibody patenting, under the current considerations on the 'antibody exception'.

Keywords: antibody exception, antibody patent, USPTO (U. S. Patent and Trademark Offices) guidelines, written description requirement

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1220 Computational Investigation of V599 Mutations of BRAF Protein and Its Control over the Therapeutic Outcome under the Malignant Condition

Authors: Mayank, Navneet Kaur, Narinder Singh

Abstract:

The V599 mutations in the BRAF protein are extremely oncogenic, responsible for countless of malignant conditions. Along with wild type, V599E, V599D, and V599R are the important mutated variants of the BRAF proteins. The BRAF inhibitory anticancer agents are continuously developing, and sorafenib is a BRAF inhibitor that is under clinical use. The crystal structure of sorafenib bounded to wild type, and V599 is known, showing a similar interaction pattern in both the case. The mutated 599th residue, in both the case, is also found not interacting directly with the co-crystallized sorafenib molecule. However, the IC50 value of sorafenib was found extremely different in both the case, i.e., 22 nmol/L for wild and 38 nmol/L for V599E protein. Molecular docking study and MMGBSA binding energy results also revealed a significant difference in the binding pattern of sorafenib in both the case. Therefore, to explore the role of distinctively situated 599th residue, we have further conducted comprehensive computational studies. The molecular dynamics simulation, residue interaction network (RIN) analysis, and residue correlation study results revealed the importance of the 599th residue on the therapeutic outcome and overall dynamic of the BRAF protein. Therefore, although the position of 599th residue is very much distinctive from the ligand-binding cavity of BRAF, still it has exceptional control over the overall functional outcome of the protein. The insight obtained here may seem extremely important and guide us while designing ideal BRAF inhibitory anticancer molecules.

Keywords: BRAF, oncogenic, sorafenib, computational studies

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