Search results for: injectable designs for new drugs

Authors: De-Shin Liu, Po-Chun Wen, Zhen-Wei Zhuang, Hsueh-Chih Liu, Pei-Chen Huang

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Wafer probing tests play an important role in semiconductor manufacturing procedures in accordance with the yield and reliability requirement of the wafer after the backend-of-the-line process. Accordingly, the stable physical and electrical contact between the probe and the tested wafer during wafer probing is regarded as an essential issue in identifying the known good die. The probe card can be integrated with multiple probe needles, which are classified as vertical, cantilever and micro-electro-mechanical systems type probe selections. Among all potential probe types, the vertical probe has several advantages as compared with other probe types, including maintainability, high probe density and feasibility for high-speed wafer testing. In the present study, the mechanical response of the wafer probing test with the vertical cobra probe on 720 μm thick silicon (Si) substrate with a 1.4 μm thick aluminum (Al) pad is investigated by the experiment and transient dynamic simulation approach. Because the deformation mechanism of the vertical cobra probe is determined by both bending and buckling mechanisms, the stable correlation between contact forces and overdrive (OD) length must be carefully verified. Moreover, the decent OD length with corresponding contact force contributed to piercing the native oxide layer of the Al pad and preventing the probing test-induced damage on the interconnect system. Accordingly, the scratch depth of the Al pad under various OD lengths is estimated by the atomic force microscope (AFM) and simulation work. In the wafer probing test configuration, the contact phenomenon between the probe needle and the tested object introduced large deformation and twisting of mesh gridding, causing the subsequent numerical divergence issue. For this reason, the arbitrary Lagrangian-Eulerian method is utilized in the present simulation work to conquer the aforementioned issue. The analytic results revealed a slight difference when the OD is considered as 40 μm, and the simulated is almost identical to the measured scratch depths of the Al pad under higher OD lengths up to 70 μm. This phenomenon can be attributed to the unstable contact of the probe at low OD length with the scratch depth below 30% of Al pad thickness, and the contact status will be being stable when the scratch depth over 30% of pad thickness. The splash of the Al pad is observed by the AFM, and the splashed Al debris accumulates on a specific side; this phenomenon is successfully simulated in the transient dynamic simulation. Thus, the preferred testing OD lengths are found as 45 μm to 70 μm, and the corresponding scratch depths on the Al pad are represented as 31.4% and 47.1% of Al pad thickness, respectively. The investigation approach demonstrated in this study contributed to analyzing the mechanical response of wafer probing test configuration under large strain conditions and assessed the geometric designs and material selections of probe needles to meet the requirement of high resolution and high-speed wafer-level probing test for thinned wafer application.

Keywords: wafer probing test, vertical probe, probe mark, mechanical response, FEA simulation

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Authors: Wai Yan Shih, Sau Man Wong, Wing Chung Chang, Wai Chi Chan

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Background: Late-life depression is associated with significant consequences. Although symptomatic reduction is achievable through pharmacological interventions, older adults are more vulnerable to the side effects than their younger counterparts. In addition, drugs do not address underlying cognitive dysfunctions such as rumination and reduced autobiographical memory specificity (AMS), both shown to be maladaptive coping styles that are associated with a poorer prognosis in depression. Considering how aging is accompanied by cognitive, psychological and physical changes, the interplay of these age-related factors may potentially aggravate and interfere with these depressive cognitive dysfunctions in late-life depression. Special care should, therefore, be drawn to ensure these cognitive dysfunctions are adequately addressed. Aim: This randomized controlled trial aims to examine the effect of mindfulness-based cognitive therapy (MBCT) on depressed older adults, and whether the potential benefits of MBCT are mediated by improvements in rumination and AMS. Method: Fifty-seven participants with an average age of 70 years old were recruited from multiple elderly centers and online mailing lists. Participants were assessed with: (1) Hamilton depression scale, (2) ruminative response scale, (3) autobiographical memory test, (4) mindful attention awareness scale, and (5) Montreal cognitive assessment. Eligible participants with mild to moderate depressive symptoms and normal cognitive functioning were randomly allocated to an 8-week MBCT group or active control group consisting of a low-intensity exercise program and health education. Post-intervention assessments were conducted after the 8-week program. Ethics approval was given by the Institutional Review Board of the University of Hong Kong/Hospital Authority. Results: Mixed-factorials ANOVAs demonstrated significant time x group interaction effects for depressive symptoms, AMS, and dispositional mindfulness. A marginally significant interaction effect was found for rumination. Simple effect analyses revealed a significant reduction in depressive symptoms for the both the MBCT group (mean difference = 7.1, p = .000), and control group (mean difference = 2.7, p = .023). However, only participants in the MBCT group demonstrated improvements in rumination, AMS, and dispositional mindfulness. Bootstrapping-based mediation analyses showed that the effect of MBCT in alleviating depressive symptoms was only mediated by the reduction in rumination. Conclusions: The findings support the use of MBCT as an effective intervention for depressed older adults, considering the improvements in depressive symptoms, rumination, AMS and dispositional mindfulness despite their age. Reduction in ruminative tendencies plays a major role in the cognitive mechanism of MBCT.

Keywords: mindfulness-based cognitive therapy, depression, older adults, rumination, autobiographical memory specificity

Procedia PDF Downloads 196

Authors: Shiamaa Eltantawy, Gihan Sobhy, Alif Alaam

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Wilson disease, or hepatolenticular degeneration, is an autosomal recessive disease that results in excess copper buildup in the body. It primarily affects the liver and basal ganglia of the brain, but it can affect other organ systems. Musculoskeletal abnormalities, including premature osteoarthritis, skeletal deformity, and pathological bone fractures, can occasionally be found in WD patients with a hepatic or neurologic type. The aim was to assess the prevalence of osteoporosis and osteopenia in Wilson’s disease patients. This case-control study was conducted on ninety children recruited from the inpatient ward and outpatient clinic of the Paediatric Hepatology, Gastroenterology, and Nutrition department of the National Liver Institute at Menofia University, aged from 1 to 18 years. Males were 49, and females were 41. Children were divided into three groups: (Group I) consisted of thirty patients with WD; (Group II) consisted of thirty patients with chronic liver disease other than WD; (Group III) consisted of thirty age- and sex-matched healthy The exclusion criteria were patients with hyperparathyroidism, hyperthyroidism, renal failure, Cushing's syndrome, and patients on certain drugs such as chemotherapy, anticonvulsants, or steroids. All patients were subjected to the following: 1- Full history-taking and clinical examination. 2-Laboratory investigations: (FBC,ALT,AST,serum albumin, total protein, total serum bilirubin,direct bilirubin,alkaline phosphatase, prothrombin time, serum critine,parathyroid hormone, serum calcium, serum phosphrus). 3-Bone mineral density (BMD, gm/cm2) values were measured by dual-energy X-ray absorptiometry (DEXA). The results revealed that there was a highly statistically significant difference between the three groups regarding the DEXA scan, and there was no statistically significant difference between groups I and II, but the WD group had the lowest bone mineral density. The WD group had a large number of cases of osteopenia and osteoporosis, but there was no statistically significant difference with the group II mean, while a high statistically significant difference was found when compared to group III. In the WD group, there were 20 patients with osteopenia, 4 patients with osteoporosis, and 6 patients who were normal. The percentages were 66.7%, 13.3%, and 20%, respectively. Therefore, the largest number of cases in the WD group had osteopenia. There was no statistically significant difference found between WD patients on different treatment regimens regarding DEXA scan results (Z-Score). There was no statistically significant difference found between patients in the WD group (normal, osteopenic, or osteoporotic) regarding phosphorus (mg/dL), but there was a highly statistically significant difference found between them regarding ionised Ca (mmol/L). Therefore, there was a decrease in bone mineral density when the Ca level was decreased. In summary, Wilson disease is associated with bone demineralization. The largest number of cases in the WD group in our study had osteopenia (66.7%). Different treatment regimens (zinc monotherapy, Artamin, and zinc) as well as different laboratory parameters have no effect on bone mineralization in WD cases. Decreased ionised Ca is associated with low BMD in WD patients. Children with WD should be investigated for BMD.

Keywords: wilson disease, Bone mineral density, liver disease, osteoporosis

Procedia PDF Downloads 39

Authors: D. S. N. K. Liyanagamage, V. Karunaratne, A. P. Attanayake, S. Jayasinghe

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Diabetes mellitus is an ever increasing global health problem which causes disability and untimely death. Current treatments using synthetic drugs have caused numerous adverse effects as well as complications, leading research efforts in search of safe and effective alternative treatments for diabetes mellitus. Even though there are traditional Ayurvedic remedies which are effective, due to a lack of scientific exploration, they have not been proven to be beneficial for common use. Hence the aim of this study is to evaluate the traditional remedy made of mixture of plant components, namely leaves of Murraya koenigii L. Spreng (Rutaceae), cloves of Allium sativum L. (Amaryllidaceae), fruits of Garcinia queasita Pierre (Clusiaceae) and seeds of Piper nigrum L. (Piperaceae) used for the treatment of diabetes. We report herein the preliminary results for the in vivo study of the anti-hyperglycaemic activity of the extracts of the above plant mixture in Wistar rats. A mixture made out of equal weights (100 g) of the above mentioned medicinal plant parts were extracted into cold water, hot water (3 h reflux) and water: acetone mixture (1:1) separately. Male wistar rats were divided into six groups that received different treatments. Diabetes mellitus was induced by intraperitoneal administration of streptozotocin at a dose of 70 mg/ kg in male Wistar rats in group two, three, four, five and six. Group one (N=6) served as the healthy untreated and group two (N=6) served as diabetic untreated control and both groups received distilled water. Cold water, hot water, and water: acetone plant extracts were orally administered in diabetic rats in groups three, four and five, respectively at different doses of 0.5 g/kg (n=6), 1.0 g/kg(n=6) and 1.5 g/kg(n=6) for each group. Glibenclamide (0.5 mg/kg) was administered to diabetic rats in group six (N=6) served as the positive control. The acute anti-hyperglycemic effect was evaluated over a four hour period using the total area under the curve (TAUC) method. The results of the test group of rats were compared with the diabetic untreated control. The TAUC of healthy and diabetic rats were 23.16 ±2.5 mmol/L.h and 58.31±3.0 mmol/L.h, respectively. A significant dose dependent improvement in acute anti-hyperglycaemic activity was observed in water: acetone extract (25%), hot water extract ( 20 %), and cold water extract (15 %) compared to the diabetic untreated control rats in terms of glucose tolerance (P < 0.05). Therefore, the results suggest that the plant mixture has a potent antihyperglycemic effect and thus validating their used in Ayurvedic medicine for the management of diabetes mellitus. Future studies will be focused on the determination of the long term in vivo anti-diabetic mechanisms and isolation of bioactive compounds responsible for the anti-diabetic activity.

Keywords: acute antihyperglycemic activity, herbal mixture, oral glucose tolerance test, Sri Lankan medicinal plant extracts

Procedia PDF Downloads 161

Authors: Stephanie Wall, Guido Wimmers

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The construction and operation of buildings greatly contribute to environmental degradation through resource and energy consumption and greenhouse gas emissions. The design of the envelope system affects the environmental impact of a building in two major ways; 1) high thermal performance and air tightness can significantly reduce the operational energy of the building and 2) the material selection for the envelope largely impacts the embodied energy of the building. Life cycle assessment (LCA) is a scientific methodology that is used to systematically analyze the environmental load of processes or products, such as buildings, over their life. The paper will discuss the results of a comparative LCA of different envelope designs and the long-term monitoring of the Wood Innovation Research Lab (WIRL); a Passive House (PH), industrial building under construction in Prince George, Canada. The WIRL has a footprint of 30m x 30m on a concrete raft slab foundation and consists of shop space as well as a portion of the building that includes a two-story office/classroom space. The lab building goes beyond what was previously thought possible in regards to energy efficiency of industrial buildings in cold climates due to their large volume to surface ratio, small floor area, and high air change rate, and will be the first PH certified industrial building in Canada. These challenges were mitigated through the envelope design which utilizes solar gains while minimizing overheating, reduces thermal bridges with thick (570mm) prefabricated truss walls filled with blown in mineral wool insulation and a concrete slab and roof insulated with EPS rigid insulation. The envelope design results in lower operational and embodied energy when compared to buildings built to local codes or with steel. The LCA conducted using Athena Impact Estimator for Buildings identifies project specific hot spots as well illustrates that for high-efficiency buildings where the operational energy is relatively low; the embodied energy of the material selection becomes a significant design decision as it greatly impacts the overall environmental footprint of the building. The results of the LCA will be reinforced by long-term monitoring of the buildings envelope performance through the installation of temperature and humidity sensors throughout the floor slab, wall and roof panels and through detailed metering of the energy consumption. The data collected from the sensors will also be used to reinforce the results of hygrothermal analysis using WUFI®, a program used to verify the durability of the wall and roof panels. The WIRL provides an opportunity to showcase the use of wood in a high performance envelope of an industrial building and to emphasize the importance of considering the embodied energy of a material in the early stages of design. The results of the LCA will be of interest to leading researchers and scientists committed to finding sustainable solutions for new construction and high-performance buildings.

Keywords: high performance envelope, life cycle assessment, long term monitoring, passive house, prefabricated panels

Procedia PDF Downloads 146

Authors: Animesh Pan, Geoffrey D. Bothun

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With the development of nanotechnology, research in multifunctional delivery systems has a new pace and dimension. An incipient challenge is to design an all-in-one delivery system that can be used for multiple purposes, including tumor targeting therapy, radio-frequency (RF-), near-infrared (NIR-), light-, or pH-induced controlled release, photothermal therapy (PTT), photodynamic therapy (PDT), and medical diagnosis. In this regard, various inorganic nanoparticles (NPs) are known to show great potential as the 'functional components' because of their fascinating and tunable physicochemical properties and the possibility of multiple theranostic modalities from individual NPs. Magnetic, luminescent, and plasmonic properties are the three most extensively studied and, more importantly biomedically exploitable properties of inorganic NPs. Although successful attempts of combining any two of them above mentioned functionalities have been made, integrating them in one system has remained challenge. Keeping those in mind, controlled designs of complex colloidal nanoparticle system are one of the most significant challenges in nanoscience and nanotechnology. Therefore, systematic and planned studies providing better revelation are demanded. We report a multifunctional delivery platform-based liposome loaded with drug, iron-oxide magnetic nanoparticles (MNPs), and a gold shell on the surface of liposomes, were synthesized using a lipid with polyelectrolyte (layersomes) templating technique. MNPs and the anti-cancer drug doxorubicin (DOX) were co-encapsulated inside liposomes composed by zwitterionic phophatidylcholine and anionic phosphatidylglycerol using reverse phase evaporation (REV) method. The liposomes were coated with positively charge polyelectrolyte (poly-L-lysine) to enrich the interface with gold anion, exposed to a reducing agent to form a gold nanoshell, and then capped with thio-terminated polyethylene glycol (SH-PEG2000). The core-shell nanostructures were characterized by different techniques like; UV-Vis/NIR scanning spectrophotometer, dynamic light scattering (DLS), transmission electron microscope (TEM). This multifunctional system achieves a variety of functions, such as radiofrequency (RF)-triggered release, chemo-hyperthermia, and NIR laser-triggered for photothermal therapy. Herein, we highlight some of the remaining major design challenges in combination with preliminary studies assessing therapeutic objectives. We demonstrate an efficient loading and delivery system to significant cell death of human cancer cells (A549) with therapeutic capabilities. Coupled with RF and NIR excitation to the doxorubicin-loaded core-shell nanostructure helped in securing targeted and controlled drug release to the cancer cells. The present core-shell multifunctional system with their multimodal imaging and therapeutic capabilities would be eminent candidates for cancer theranostics.

Keywords: cancer thernostics, multifunctional nanostructure, photothermal therapy, radiofrequency targeting

Procedia PDF Downloads 112

Authors: Nigar Kantarci Carsibasi

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Coarse-grained elastic network models, namely Gaussian network model (GNM) and Anisotropic network model (ANM), are utilized in order to investigate the fluctuation dynamics of Murine Double Minute 2 (MDM2), which is the native inhibitor of p53. Conformational dynamics of MDM2 are elucidated in unbound, p53 bound, and non-peptide small molecule inhibitor bound forms. With this, it is aimed to gain insights about the alterations brought to global dynamics of MDM2 by native peptide inhibitor p53, and two small molecule inhibitors (HDM201 and NVP-CGM097) that are undergoing clinical stages in cancer studies. MDM2 undergoes significant conformational changes upon inhibitor binding, carrying pieces of evidence of induced-fit mechanism. Small molecule inhibitors examined in this work exhibit similar fluctuation dynamics and characteristic mode shapes with p53 when complexed with MDM2, which would shed light on the design of novel small molecule inhibitors for cancer therapy. The results showed that residues Phe 19, Trp 23, Leu 26 reside in the minima of slowest modes of p53, pointing to the accepted three-finger binding model. Pro 27 displays the most significant hinge present in p53 and comes out to be another functionally important residue. Three distinct regions are identified in MDM2, for which significant conformational changes are observed upon binding. Regions I (residues 50-77) and III (residues 90-105) correspond to the binding interface of MDM2, including (α2, L2, and α4), which are stabilized during complex formation. Region II (residues 77-90) exhibits a large amplitude motion, being highly flexible, both in the absence and presence of p53 or other inhibitors. MDM2 exhibits a scattered profile in the fastest modes of motion, while binding of p53 and inhibitors puts restraints on MDM2 domains, clearly distinguishing the kinetically hot regions. Mode shape analysis revealed that the α4 domain controls the size of the cleft by keeping the cleft narrow in unbound MDM2; and open in the bound states for proper penetration and binding of p53 and inhibitors, which points to the induced-fit mechanism of p53 binding. P53 interacts with α2 and α4 in a synchronized manner. Collective modes are shifted upon inhibitor binding, i.e., second mode characteristic motion in MDM2-p53 complex is observed in the first mode of apo MDM2; however, apo and bound MDM2 exhibits similar features in the softest modes pointing to pre-existing modes facilitating the ligand binding. Although much higher amplitude motions are attained in the presence of non-peptide small molecule inhibitor molecules as compared to p53, they demonstrate close similarity. Hence, NVP-CGM097 and HDM201 succeed in mimicking the p53 behavior well. Elucidating how drug candidates alter the MDM2 global and conformational dynamics would shed light on the rational design of novel anticancer drugs.

Keywords: cancer, drug design, elastic network model, MDM2

Procedia PDF Downloads 115

Authors: Doris C. C. K. Kowaltowski, Marcella S. Deliberador

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The architectural design process, in general, is becoming more complex, as new technical, social, environmental, and economical requirements are imposed. For school buildings, this scenario is also valid. The quality of a school building depends on known design criteria and professional knowledge, as well as feedback from building performance assessments. To attain high-performance school buildings, a design process should add a multidisciplinary team, through an integrated process, to ensure that the various specialists contribute at an early stage to design solutions. The participation of stakeholders is of special importance at the programming phase when the search for the most appropriate design solutions is underway. The composition of a multidisciplinary team should comprise specialists in education, design professionals, and consultants in various fields such as environmental comfort and psychology, sustainability, safety and security, as well as administrators, public officials and neighbourhood representatives. Users, or potential users (teachers, parents, students, school officials, and staff), should be involved. User expectations must be guided, however, toward a proper understanding of a response of design to needs to avoid disappointment. In this context, appropriate tools should be introduced to organize such diverse participants and ensure a rich and focused response to needs and a productive outcome of programming sessions. In this paper, different stakeholder in a school design process are discussed in relation to their specific contributions and a tool in the form of a card game is described to structure the design debates and ensure a comprehensive decision-making process. The game is based on design patterns for school architecture as found in the literature and is adapted to a specific reality: State-run public schools in São Paulo, Brazil. In this State, school buildings are managed by a foundation called Fundação para o Desenvolvimento da Educação (FDE). FDE supervises new designs and is responsible for the maintenance of ~ 5000 schools. The design process of this context was characterised with a recommendation to improve the programming phase. Card games can create a common environment, to which all participants can relate and, therefore, can contribute to briefing debates on an equal footing. The cards of the game described here represent essential school design themes as found in the literature. The tool was tested with stakeholder groups and with architecture students. In both situations, the game proved to be an efficient tool to stimulate school design discussions and to aid in the elaboration of a rich, focused and thoughtful architectural program for a given demand. The game organizes the debates and all participants are shown to spontaneously contribute each in his own field of expertise to the decision-making process. Although the game was specifically based on a local school design process it shows potential for other contexts because the content is based on known facts, needs and concepts of school design, which are global. A structured briefing phase with diverse stakeholder participation can enrich the design process and consequently improve the quality of school buildings.

Keywords: architectural program, design process, school building design, stakeholder

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Authors: Meenu S. Babu, K. Jayasankara Reddy

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Depression is a serious mental health concern that leads to significant distress and dysfunction in an individual. Due to the high physical, psychological, social, and economic burden it causes, it is important to study various bio-psycho-social factors that influence the onset, course, duration, intensity of depressive symptoms. The study aims to explore relationship between autobiographical memory (AM) functions, perceived control over stressful events and depressive symptoms. AM functions and perceived control were both found to be protective factors for individuals against depression and were both modifiable to predict better behavioral and affective outcomes. An extensive review of literatur, with a systematic search on Google Scholar, JSTOR, Science Direct and Springer Journals database, was conducted for the purpose of this review paper. These were used for all the aforementioned databases. The time frame used for the search was 2010-2021. An additional search was conducted with no time bar to map the development of the theoretical concepts. The relevant studies with quantitative, qualitative, experimental, and quasi- experimental research designs were included for the review. Studies including a sample with a DSM- 5 or ICD-10 diagnosis of depressive disorders were excluded from the study to focus on the behavioral patterns in a non-clinical population. The synthesis of the findings that were obtained from the review indicates there is a significant relationship between cognitive variables of AM functions and perceived control and depressive symptoms. AM functions were found to be have significant effects on once sense of self, interpersonal relationships, decision making, self- continuity and were related to better emotion regulation and lower depressive symptoms. Not all the components of AM function were equally significant in their relationships with various depressive symptoms. While self and directive functions were more related to emotion regulation, anhedonia, motivation and hence mood and affect, the social function was related to perceived social support and social engagement. Perceived control was found to be another protective cognitive factor that provides individuals a sense of agency and control over one’s life outcomes which was found to be low in individuals with depression. This was also associated to the locus of control, competency beliefs, contingency beliefs and subjective well being in individuals and acted as protective factors against depressive symptoms. AM and perceived control over stressful events serve adaptive functions, hence it is imperative to study these variables more extensively. They can be imperative in planning and implementing therapeutic interventions to foster these cognitive protective factors to mitigate or alleviate depressive symptoms. Exploring AM as a determining factor in depressive symptoms along with perceived control over stress creates a bridge between biological and cognitive factors underlying depression and increases the scope of developing a more eclectic and effective treatment plan for individuals. As culture plays a crucial role in AM functions as well as certain aspects of control such as locus of control, it is necessary to study these variables keeping in mind the cultural context to tailor culture/community specific interventions for depression.

Keywords: autobiographical memories, autobiographical memory functions, perceived control, depressive symptoms, depression, young adults

Procedia PDF Downloads 85

Authors: Milu T. Cherian, Sergio C. Chai, Morgan A. Casal, Taosheng Chen

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This study aims to use CINPA1, a recently discovered small-molecule inhibitor of the xenobiotic receptor CAR (constitutive androstane receptor) for understanding the binding modes of CAR and to guide CAR-mediated gene expression profiling studies in human primary hepatocytes. CAR and PXR are xenobiotic sensors that respond to drugs and endobiotics by modulating the expression of metabolic genes that enhance detoxification and elimination. Elevated levels of drug metabolizing enzymes and efflux transporters resulting from CAR activation promote the elimination of chemotherapeutic agents leading to reduced therapeutic effectiveness. Multidrug resistance in tumors after chemotherapy could be associated with errant CAR activity, as shown in the case of neuroblastoma. CAR inhibitors used in combination with existing chemotherapeutics could be utilized to attenuate multidrug resistance and resensitize chemo-resistant cancer cells. CAR and PXR have many overlapping modulating ligands as well as many overlapping target genes which confounded attempts to understand and regulate receptor-specific activity. Through a directed screening approach we previously identified a new CAR inhibitor, CINPA1, which is novel in its ability to inhibit CAR function without activating PXR. The cellular mechanisms by which CINPA1 inhibits CAR function were also extensively examined along with its pharmacokinetic properties. CINPA1 binding was shown to change CAR-coregulator interactions as well as modify CAR recruitment at DNA response elements of regulated genes. CINPA1 was shown to be broken down in the liver to form two, mostly inactive, metabolites. The structure-activity differences of CINPA1 and its metabolites were used to guide computational modeling using the CAR-LBD structure. To rationalize how ligand binding may lead to different CAR pharmacology, an analysis of the docked poses of human CAR bound to CITCO (a CAR activator) vs. CINPA1 or the metabolites was conducted. From our modeling, strong hydrogen bonding of CINPA1 with N165 and H203 in the CAR-LBD was predicted. These residues were validated to be important for CINPA1 binding using single amino-acid CAR mutants in a CAR-mediated functional reporter assay. Also predicted were residues making key hydrophobic interactions with CINPA1 but not the inactive metabolites. Some of these hydrophobic amino acids were also identified and additionally, the differential coregulator interactions of these mutants were determined in mammalian two-hybrid systems. CINPA1 represents an excellent starting point for future optimization into highly relevant probe molecules to study the function of the CAR receptor in normal- and pathophysiology, and possible development of therapeutics (for e.g. use for resensitizing chemoresistant neuroblastoma cells).

Keywords: antagonist, chemoresistance, constitutive androstane receptor (CAR), multi-drug resistance, structure activity relationship (SAR), xenobiotic resistance

Procedia PDF Downloads 266

Authors: Geremew Geidare Kailo, Igor Gáspár, András Koris, Ivana Pajčin, Flóra Vitális, Vanja Vlajkov

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Three-dimension (3D) printing, a very popular additive manufacturing technology, has recently undergone rapid growth and replaced the use of conventional technology from prototyping to producing end-user parts and products. The 3D Printing technology involves a digital manufacturing machine that produces three-dimensional objects according to designs created by the user via 3D modeling or computer-aided design/manufacturing (CAD/CAM) software. The most popular 3D printing system is Fused Deposition Modeling (FDM) or also called Fused Filament Fabrication (FFF). A 3D-printed object is considered food safe if it can have direct contact with the food without any toxic effects, even after cleaning, storing, and reusing the object. This work analyzes the processing timeline of the filament (material for 3D printing) from unboxing to the extrusion through the nozzle. It is an important task to analyze the growth of bacteria on the 3D printed surface and in gaps between the layers. By default, the 3D-printed object is not food safe after longer usage and direct contact with food (even though they use food-safe filaments), but there are solutions for this problem. The aim of this work was to evaluate the 3D-printed object from different perspectives of food safety. Firstly, testing antimicrobial 3D printing filaments from a food safety aspect since the 3D Printed object in the food industry may have direct contact with the food. Therefore, the main purpose of the work is to reduce the microbial load on the surface of a 3D-printed part. Coating with epoxy resin was investigated, too, to see its effect on mechanical strength, thermal resistance, surface smoothness and food safety (cleanability). Another aim of this study was to test new temperature-resistant filaments and the effect of high temperature on 3D printed materials to see if they can be cleaned with boiling or similar hi-temp treatment. This work proved that all three mentioned methods could improve the food safety of the 3D printed object, but the size of this effect variates. The best result we got was with coating with epoxy resin, and the object was cleanable like any other injection molded plastic object with a smooth surface. Very good results we got by boiling the objects, and it is good to see that nowadays, more and more special filaments have a food-safe certificate and can withstand boiling temperatures too. Using antibacterial filaments reduced bacterial colonies to 1/5, but the biggest advantage of this method is that it doesn’t require any post-processing. The object is ready out of the 3D printer. Acknowledgements: The research was supported by the Hungarian and Serbian bilateral scientific and technological cooperation project funded by the Hungarian National Office for Research, Development and Innovation (NKFI, 2019-2.1.11-TÉT-2020-00249) and the Ministry of Education, Science and Technological Development of the Republic of Serbia. The authors acknowledge the Hungarian University of Agriculture and Life Sciences’s Doctoral School of Food Science for the support in this study

Keywords: food safety, 3D printing, filaments, microbial, temperature

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

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

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

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Authors: Lakshmi N. Reddi, Akanksha Varma Sagi

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Studies on biomimetics are largely developed, deriving inspiration from natural processes in our objective world to develop novel technologies. Recent studies are diverse in nature, making their categorization quite challenging. Based on an exhaustive survey, we developed categorizations based on either the essential elements of nature - air, water, land, fire, and space, or on form/shape, functionality, and process. Such diverse studies as aircraft wings inspired by bird wings, a self-cleaning coating inspired by a lotus petal, wetsuits inspired by beaver fur, and search algorithms inspired by arboreal ant path networks lend themselves to these categorizations. Our categorizations of biomimetic studies allowed us to define a different dimension of biomimetics. This new dimension is not restricted to inspiration from the objective world. It is based on the premise that the biological processes observed in the objective world find their reflections in our human bodies in a variety of ways. For example, the lungs provide the most efficient example for liquid-gas phase exchange, the heart exemplifies a very efficient pumping and circulatory system, and the kidneys epitomize the most effective cleaning system. The main focus of this paper is to bring out the magnificence of the cerebro-spinal system (CSS) insofar as it relates to our current computer architecture. In particular, the paper uses four key measures to analyze the differences between CSS and human- engineered computational systems. These are adaptability, sustainability, energy efficiency, and resilience. We found that the cerebrospinal system reveals some important challenges in the development and evolution of our current computer architectures. In particular, the myriad ways in which the CSS is integrated with other systems/processes (circulatory, respiration, etc) offer useful insights on how the human-engineered computational systems could be made more sustainable, energy-efficient, resilient, and adaptable. In our paper, we highlight the energy consumption differences between CSS and our current computational designs. Apart from the obvious differences in materials used between the two, the systemic nature of how CSS functions provides clues to enhance life-cycles of our current computational systems. The rapid formation and changes in the physiology of dendritic spines and their synaptic plasticity causing memory changes (ex., long-term potentiation and long-term depression) allowed us to formulate differences in the adaptability and resilience of CSS. In addition, the CSS is sustained by integrative functions of various organs, and its robustness comes from its interdependence with the circulatory system. The paper documents and analyzes quantifiable differences between the two in terms of the four measures. Our analyses point out the possibilities in the development of computational systems that are more adaptable, sustainable, energy efficient, and resilient. It concludes with the potential approaches for technological advancement through creation of more interconnected and interdependent systems to replicate the effective operation of cerebro-spinal system.

Keywords: cerebrospinal system, computer architecture, adaptability, sustainability, resilience, energy efficiency

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Authors: Lina Shinhwa Koo

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The Korean Empire, or Daehanjeguk, was proclaimed by King Gojong (1852–1919) in 1897 with the aim of promoting its sovereignty as a nation-state amid the political situation with threats from neighbouring countries, such as Japan and Russia. The Korean Empire period (1897–1910), which lasted until 1910, when Japan annexed Korea, is a pivotal time in the modern history of Korea. It was also during the period when many infrastructures for tourism, including transportation and lodging systems, were established. Throughout the Korean Empire period, tourists from Japan and Euro-American countries popularly visited Korea after it opened its doors relatively recently. The government of the Korean Empire also actively engaged with foreign officials and professionals. Train stations were built to connect Busan, where foreigners first arrived through the port of Jemulpo, with Seoul, the capital of Korea. In addition, hotels were built to accommodate the increasing number of tourists. Shedding new light on the modern architectural history of Korea, this paper discusses buildings that were made for tourism during the Korean Empire period to examine the historical background behind the tourism development in Korea and the concept of travelling related to architecture history. Foreigners came to Korea for varying reasons, from ethnographic research and diplomacy to business and missionary. They also played a key role in the transportation and hotel businesses. For instance, American entrepreneur James R. Morse received a concession to construct a railway between Busan and Seoul in 1896, which was later granted to a Japanese firm. Japanese entrepreneurs came to Korea and built hotels, such as Daebul Hotel in Incheon and Paseonggwan in Seoul. Sontag Hotel, Station Hotel and Hotel du Palais, all located in central areas of Seoul, were owned by German, British and French entrepreneurs, respectively. Each building showed distinctive architectural elements. For example, Sontag Hotel was built in Russian architectural style, whereas Paseonggwan was created with a combination of Japanese and European styles. Such various architectural designs indicated the multicultural urban scenes of the Korean Empire at the time. The existing scholarship has paid more attention to the royal buildings built during the Korean Empire period, such as Seokjojeon of the Duksu Palace. However, it is important to study the tourism-related architecture that reflected the societal situation of the Korean Empire when contrasting ideologies, landscapes, historical narratives and political tensions intertwined and co-existed. Examining both textual and visual resources, such as news articles and photographs, this paper surveys architectural styles and the trajectories of selective examples of hotels and train stations within the discussion of temporality and spatiality in the discipline of social science. In doing so, one can re-assess the history of the Korean Empire as the intersection of modern and traditional, intrinsic and extrinsic and national and international.

Keywords: Korean empire, modern Korean architecture, tourism, hotel, train station

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Authors: Ružica Tomičić, Zorica Tomičić, Peter Raspor

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An abundant growth of unwanted yeasts in food processing plants can lead to problems in quality and safety with significant financial losses. Candida and Pichia are the genera mainly involved in spoilage of products in the food and beverage industry. These contaminating microorganisms can form biofilms on food contact surfaces, being difficult to eradicate, increasing the probability of microbial survival and further dissemination during food processing. It is well known that biofilms are more resistant to antimicrobial agents compared to planktonic cells and this makes them difficult to eliminate. Among the strategies used to overcome resistance to antifungal drugs and preservatives, the use of natural substances such as plant extracts has shown particular promise, and many natural substances have been found to exhibit antifungal properties. This study aimed to investigated the impact of growth medium (Malt Extract broth (MEB) or Yeast Peptone Dextrose (YPD) broth) and temperatures (7°C, 37°C, 43°C for Candida strains and 7°C, 27°C, 32°C for Pichia strains) on the adhesion of Candida spp. and Pichia spp. to stainless steel (AISI 304) discs with different degrees of surface roughness (Ra = 25.20 – 961.9 nm), a material commonly used in the food industry. We also evaluated the antifungal and antiadhesion activity of plant extracts such as Humulus lupulus, Alpinia katsumadai and Evodia rutaecarpa against C. albicans, C glabrata and P. membranifaciens and investigated whether these plant extracts can interfere with biofilm formation. The adhesion was assessed by the crystal violet staining method, while the broth microdilution method CLSI M27-A3 was used to determine the minimum inhibitory concentration (MIC) of plant extracts. Our results indicated that the nutrient content of the medium significantly influenced the amount of adhered cells of the tested yeasts. The growth medium which resulted in a higher adhesion of C. albicans and C. glabrata was MEB, while for C. parapsilosis and C. krusei was YPD. In the case of P. pijperi and P. membranifaciens, YPD broth was more effective in promoting adhesion than MEB. Regarding the effect of temperature, C. albicans strain adhered to stainless steel surfaces in significantly higher level at a temperature of 43°C, while on the other hand C. glabrata, C. parapsilosis and C. krusei showed a different behavior with significantly higher adhesion at 37°C than at 7°C and 43°C. Further, the adherence ability of Pichia strains was highest at 27°C. Based on the MIC values, all plant extracts exerted significant antifungal effects with MIC values ranged from 100 to 400 μg/mL. It was observed that biofilm of C. glabrata were more resistance to plant extracts as compared to C. albicans. However, extracts of A. katsumadai and E. rutaecarpa promoted the growth and development of the preformed biofilm of P. membranifaciens. Thus, the knowledge of how these microorganisms adhere and which factors affect this phenomenon is of great importance in order to avoid their colonization on food contact surfaces.

Keywords: adhesion, Candida spp., Pichia spp., plant extracts

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Authors: Shahira M. Ezzat, Marwa I. Ezzat, Mona M. Okba, Esther T. Menze, Ashraf B. Abdel-Naim, Shahnas O. Mohamed

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Background: In order to decrease the burden of the high cost of synthetic drugs, it is important to focus on phytopharmaceuticals. The aim of our study was to search for the mechanism of ginger (Zingiber officinale Roscoe) anti-inflammatory potential and to correlate it to its biophytochemicals. Methods: Various extracts viz. water, 50%, 70%, 80%, and 90% ethanol were prepared from ginger rhizomes. Fractionation of the aqueous extract (AE) was accomplished using Diaion HP-20. In vitro anti-inflammatory activity of the different extracts and isolated compounds was evaluated by protein denaturation inhibition, membrane stabilization, protease inhibition, and anti-lipoxygenase assays. In vivo anti-inflammatory activity of AE was estimated by assessment of rat paw oedema after carrageenan injection. Prostaglandin E2 (PGE2), certain inflammation markers (TNF-α, IL-6, IL-1α, IL-1β, INFr, MCP-1MIP, RANTES, and Nox) levels and MPO activity in the paw edema exudates were measured. Total antioxidant capacity (TAC) was also determined. Histopathological alterations of paw tissues were scored. Results: All the tested extracts showed significant (p < 0.1) anti-inflammatory activities. The highest percentage of heat induced albumin denaturation (66%) was exhibited by the 50% ethanol (250 μg/ml). The 70 and 90% ethanol extracts (500 μg/ml) were more potent as membrane stabilizers (34.5 and 37%, respectively) than diclofenac (33%). The 80 and 90% ethanol extracts (500 μg/ml) showed maximum protease inhibition (56%). The strongest anti-lipoxygenase activity was observed for the AE. It showed more significant lipoxygenase inhibition activity than that of diclofenac (58% and 52%, respectively) at the same concentration (125 μg/ml). Fractionation of AE yielded four main fractions (Fr I-IV) which showed significant in vitro anti-inflammatory. Purification of Fr-III and IV led to the isolation of 6-poradol (G1), 6-shogaol (G2); methyl 6- gingerol (G3), 5-gingerol (G4), 6-gingerol (G5), 8-gingerol (G6), 10-gingerol (G7), and 1-dehydro-6-gingerol (G8). G2 (62.5 ug/ml), G1 (250 ug/ml), and G8 (250 ug/ml) exhibited potent anti-inflammatory activity in all studied assays, while G4 and G5 exhibited moderate activity. In vivo administration of AE ameliorated rat paw oedema in a dose-dependent manner. AE (at 200 mg/kg) showed significant reduction (60%) of PGE2 production. The AE at different doses (at 25-200 mg/kg) showed significant reduction in inflammatory markers except for IL-1α. AE (at 25 mg/kg) is superior to indomethacin in reduction of IL-1β. Treatment of animals with the AE (100, 200 mg/kg) or indomethacin (10 mg/kg) showed significant reduction in TNF-α, IL-6, MCP-1, and RANTES levels, and MPO activity by about (31, 57 and 32% ) (65, 60 and 57%) (27, 41 and 28%) (23, 32 and 23%) (66, 67 and 67%) respectively. AE at 100 and 200 mg/kg was equipotent to indomethacin in reduction of NOₓ level and in increasing the TAC. Histopathological examination revealed very few inflammatory cells infiltration and oedema after administration of AE (200 mg/kg) prior to carrageenan. Conclusion: Ginger anti-inflammatory activity is mediated by inhibiting macrophage and neutrophils activation as well as negatively affecting monocyte and leukocyte migration. Moreover, it produced dose-dependent decrease in pro-inflammatory cytokines and chemokines and replenished the total antioxidant capacity. We strongly recommend future investigations of ginger in the potential signal transduction pathways.

Keywords: anti-lipoxygenase activity, inflammatory markers, 1-dehydro-6-gingerol, 6-shogaol

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Authors: Kaushiki Sanyal, Rajesh Chakrabarti

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In India, on average, about 60 Bills are passed every year in both Houses of Parliament – Lok Sabha and Rajya Sabha (calculated from information on websites of both Houses). These are debated in both Lok Sabha (House of Commons) and Rajya Sabha (Council of States) before they are passed. However, lawmakers rarely use empirical evidence to make a case for a law. Most of the time, they support a law on the basis of anecdote, intuition, and common sense. While these do play a role in law-making, without the necessary empirical evidence, laws often fail to achieve their desired results. The quality of legislative debates is an indicator of the efficacy of the legislative process through which a Bill is enacted. However, the study of legislative debates has not received much attention either in India or worldwide due to the difficulty of objectively measuring the quality of a debate. Broadly, three approaches have emerged in the study of legislative debates. The rational-choice or formal approach shows that speeches vary based on different institutional arrangements, intra-party politics, and the political culture of a country. The discourse approach focuses on the underlying rules and conventions and how they impact the content of the debates. The deliberative approach posits that legislative speech can be reasoned, respectful, and informed. This paper aims to (a) develop a framework to judge the quality of debates by using the deliberative approach; (b) examine the legislative debates of three Bills passed in different periods as a demonstration of the framework, and (c) examine the broader structural issues that disincentive MPs from scrutinizing Bills. The framework would include qualitative and quantitative indicators to judge a debate. The idea is that the framework would provide useful insights into the legislators’ knowledge of the subject, the depth of their scrutiny of Bills, and their inclination toward evidence-based research. The three Bills that the paper plans to examine are as follows: 1. The Narcotics Drugs and Psychotropic Substances Act, 1985: This act was passed to curb drug trafficking and abuse. However, it mostly failed to fulfill its purpose. Consequently, it was amended thrice but without much impact on the ground. 2. The Criminal Laws (Amendment) Act, 2013: This act amended the Indian Penal Code to add a section on human trafficking. The purpose was to curb trafficking and penalise traffickers, pimps, and middlemen. However, the crime rate remains high while the conviction rate is low. 3. The Surrogacy (Regulation) Act, 2021: This act bans commercial surrogacy allowing only relatives to act as surrogates as long as there is no monetary payment. Experts fear that instead of preventing commercial surrogacy, it would drive the activity underground. The consequences would be borne by the surrogate, who would not be protected by law. The purpose of the paper is to objectively analyse the quality of parliamentary debates, get insights into how MPs understand the evidence and deliberate on steps to incentivise them to use empirical evidence.

Keywords: legislature, debates, empirical, India

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Authors: Kirti Hira, A. Sajeli Begum, S. Mahibalan, Poorna Chandra Rao

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Introduction: Cancer is one of the leading causes of death worldwide. Although existing therapy effectively kills cancer cells, they do affect normal growing cells leading to many undesirable side effects. Hence there is need to develop effective as well as safe drug molecules to combat cancer, which is possible through phyto-research. The currently available plant-derived blockbuster drugs are the example for this. In view of this, an investigation was done to identify cytotoxic lead molecules from Hedyotis umbellata (Family Rubiaceae), a widely distributed weed in India. Materials and Methods: The methanolic extract of the whole plant of H. umbellata (MHU), prepared through Soxhlet extraction method was further fractionated with diethyl ether and n-butanol, successively. MHU, ether fraction (EMHU) and butanol fraction (BMHU) were lyophilized and were tested for the cytotoxic effect using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay against non-small cell lung cancer (NSCLC) A549 cell lines. The potentially active EMHU was subjected to chromatographic purification using normal-phase silica columns, in order to isolate the responsible bioactive compounds. The isolated pure compounds were tested for their cytotoxic effect by MTT assay against A549 cells. Compound-3, which was found to be most active, was characterized using IR, 1H- and 13C-NMR and MS analysis. The study was further extended to decipher the mechanism of action of cytotoxicity of compound-3 against A549 cells through various in vitro cellular models. Cell cycle analysis was done using flow cytometry following PI (Propidium Iodide) staining. Protein analysis was done using Western blot technique. Results: Among MHU, EMHU, and BMHU, the non-polar fraction EMHU demonstrated a significant dose-dependent cytotoxic effect with IC50 of 67.7μg/ml. Chromatography of EMHU yielded seven compounds. MTT assay of isolated compounds explored compound-3 as potentially active one, which inhibited the growth of A549 cells with IC50value of 14.2μM. Further, compound-3 was identified as cedrelopsin, a coumarin derivative having molecular weight of 260. Results of in vitro mechanistic studies explained that cedrelopsin induced cell cycle arrest at G2/M phase and down-regulated the expression of G2/M regulatory proteins such as cyclin B1, cdc2, and cdc25C, dose dependently. This is the first report that explores the cytotoxic mechanism of cedrelopsin. Conclusion: Thus a potential small lead molecule, cedrelopsin isolated from H. umbellata, showing antiproliferative effect mediated by G2/M arrest in A549 cells was discovered. The effect of cedrelopsin against other cancer cell lines followed by in vivo studies can be performed in future to develop a new drug candidate.

Keywords: A549, cedrelopsin, G2/M phase, Hedyotis umbellata

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Authors: Victor Pena Ribeiro, Caroline Arruda, Jennyfer Andrea Aldana Mejia, Jairo Kenupp Bastos

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Leishmaniasis is a serious health problem around the world. The treatment of infected individuals with pentavalent antimonial drugs is the main therapeutic strategy. However, they present high toxicity and persistence side effects. Therefore, the discovery of new and safe natural-derived therapeutic agents against leishmaniasis is important. Propolis is a resin of viscous consistency produced by Apis mellifera bees from parts of plants. The main types of Brazilian propolis are green, red, yellow and brown. Thus, the aim of this work was to investigate the chemical composition and leishmanicidal properties of a brown propolis (BP). For this purpose, the hydroalcoholic crude extract of BP was obtained and was fractionated by liquid-liquid chromatography. The chemical profile of the extract and its fractions were obtained by HPLC-UV-DAD. The fractions were submitted to preparative HPLC chromatography for isolation of the major compounds of each fraction. They were analyzed by NMR for structural determination. The volatile compounds were obtained by hydrodistillation and identified by GC/MS. Promastigote forms of Leishmania amazonensis were cultivated in M199 medium and then 2×106 parasites.mL-1 were incubated in 96-well microtiter plates with the samples. The BP was dissolved in dimethyl sulfoxide (DMSO) and diluted into the medium, to give final concentrations of 1.56, 3.12, 6.25, 12.5, 25 and 50 µg.mL⁻¹. The plates were incubated at 25ºC for 24 h, and the lysis percentage was determined by using a Neubauer chamber. The bioassays were performed in triplicate, using a medium with 0.5% DMSO as a negative control and amphotericin B as a positive control. The leishimnicidal effect against promastigote forms was also evaluated at the same concentrations. Cytotoxicity experiments also were performed in 96-well plates against normal (CHO-k1) and tumor cell lines (AGP01 and HeLa) using XTT colorimetric method. Phenolic compounds, flavonoids, and terpenoids were identified in brown propolis. The major compounds were identified as follows: p-coumaric acid (24.6%) for a methanolic fraction, Artepelin-C (29.2%) for ethyl acetate fraction and the compounds of hexane fraction are in the process of structural elucidation. The major volatile compounds identified were β-caryophyllene (10.9%), germacrene D (9.7%), nerolidol (10.8%) and spathulenol (8.5%). The propolis did not show cytotoxicity against normal cell lines (CHO) with IC₅₀ > 100 μg.mL⁻¹, whereas the IC₅₀ < 10 μg.mL⁻¹ showed a potential against the AGP01 cell line, propolis did not demonstrate cytotoxicity against HeLa cell lines IC₅₀ > 100 μg.mL⁻¹. In the determination of the leishmanicidal activity, the highest (50 μg.mL⁻¹) and lowest (1.56 μg.mL⁻¹) concentrations of the crude extract caused the lysis of 76% and 45% of promastigote forms of L. amazonensis, respectively. To the amastigote form, the highest (50 μg.mL⁻¹) and lowest (1.56 μg.mL⁻¹) concentrations caused the mortality of 89% and 75% of L. amazonensis, respectively. The IC₅₀ was 2.8 μg.mL⁻¹ to amastigote form and 3.9 μg.mL⁻¹ to promastigote form, showing a promising activity against Leishmania amazonensis.

Keywords: amastigote, brown propolis, cytotoxicity, promastigote

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Authors: Angela O. Ugwu, Sunday Ocheni

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Background: Cancer-associated thrombosis (CAT) is a cause of morbidity and mortality among cancer patients. Several risk factors for developing venous thromboembolism (VTE) also coexist with cancer patients, such as chemotherapy and immobilization, thus contributing to the higher risk of VTE in cancer patients when compared to non-cancer patients. This study aimed to determine if there is any correlation between levels of some inflammatory cytokines/haematological parameters and Khorana scores of newly diagnosed chemotherapy naïve ambulatory cancer patients (CNACP). Methods: This was a cross-sectional analytical study carried out from June 2021 to May 2022. Eligible newly diagnosed cancer patients 18 years and above (case group) were enrolled consecutively from the adult Oncology Clinics of the University of Nigeria Teaching Hospital, Ituku/Ozalla (UNTH). The control group was blood donors at UNTH Ituku/Ozalla, Enugu blood bank, and healthy members of the Medical and Dental Consultants Association of Nigeria (MDCAN), UNTH Chapter. Blood samples collected from the participants were assayed for IL-6, TNF-Alpha, and haematological parameters such as haemoglobin, white blood cell count (WBC), and platelet count. Data were entered into an Excel worksheet and were then analyzed using Statistical Package for Social Sciences (SPSS) computer software version 21.0 for windows. A P value of < 0.05 was considered statistically significant. Results: A total of 200 participants (100 cases and 100 controls) were included in the study. The overall mean age of the participants was 47.42 ±15.1 (range 20-76). The sociodemographic characteristics of the two groups, including age, sex, educational level, body mass index (BMI), and occupation, were similar (P > 0.05). Following One Way ANOVA, there were significant differences between the mean levels of interleukin-6 (IL-6) (p = 0.036) and tumor necrotic factor-α (TNF-α) (p = 0.001) in the three Khorana score groups of the case group. Pearson’s correlation analysis showed a significant positive correlation between the Khorana scores and IL-6 (r=0.28, p = 0.031), TNF-α (r= 0.254, p= 0.011), and PLR (r= 0.240, p=0.016). The mean serum levels of IL-6 were significantly higher in CNACP than in the healthy controls [8.98 (8-12) pg/ml vs. 8.43 (2-10) pg/ml, P=0.0005]. There were also significant differences in the mean levels of the haemoglobin (Hb) level (P < 0.001)); white blood cell (WBC) count ((P < 0.001), and platelet (PL) count (P = 0.005) between the two groups of participants. Conclusion: There is a significant positive correlation between the serum levels of IL-6, TNF-α, and PLR and the Khorana scores of CNACP. The mean serum levels of IL-6, TNF-α, PLR, WBC, and PL count were significantly higher in CNACP than in the healthy controls. Ambulatory cancer patients with high-risk Khorana scores may benefit from anti-inflammatory drugs because of the positive correlation with inflammatory cytokines. Recommendations: Ambulatory cancer patients with 2 Khorana scores may benefit from thromboprophylaxis since they have higher Khorana scores. A multicenter study with a heterogeneous population and larger sample size is recommended in the future to further elucidate the relationship between IL-6, TNF-α, PLR, and the Khorana scores among cancer patients in the Nigerian population.

Keywords: thromboprophylaxis, cancer, Khorana scores, inflammatory cytokines, haematological parameters

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Authors: Befekadu Urga Wakayo

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Introduction: Bacterial infections represent major human and animal health problems in Ethiopia. In the face of poor antibiotic regulatory mechanisms, development of antimicrobial resistance (AMR) to commonly used drugs has become a growing health and livelihood threat in the country. Monitoring and control of AMR demand close coloration between human and veterinary services as well as other relevant stakeholders. However, risk of AMR transfer from animal to human population’s remains poorly explored in Ethiopia. This systematic research literature review attempted to give an overview on AMR challenges of bovine mastitis bacteria in Ethiopia. Methodology: A web based research literature search and analysis strategy was used. Databases are considered including; PubMed, Google Scholar, Ethiopian Veterinary Association (EVA) and Ethiopian Society of Animal Production (ESAP). The key search terms and phrases were; Ethiopia, dairy, cattle, mastitis, bacteria isolation, antibiotic sensitivity and antimicrobial resistance. Ultimately, 15 research reports were used for the current analysis. Data extraction was performed using a structured Microsoft Excel format. Frequency AMR prevalence (%) was registered directly or calculated from reported values. Statistical analysis was performed on SPSS – 16. Variables were summarized by giving frequencies (n or %), Mean ± SE and demonstrative box plots. One way ANOVA and independent t test were used to evaluate variations in AMR prevalence estimates (Ln transformed). Statistical significance was determined at p < 0.050). Results: AMR in bovine mastitis bacteria was investigated in a total of 592 in vitro antibiotic sensitivity trials involving 12 different mastitis bacteria (including 1126 Gram positive and 77 Gram negative isolates) and 14 antibiotics. Bovine mastitis bacteria exhibited AMR to most of the antibiotics tested. Gentamycin had the lowest average AMR in both Gram positive (2%) and negative (1.8%) bacteria. Gram negative mastitis bacteria showed higher mean in vitro resistance levels to; Erythromycin (72.6%), Tetracycline (56.65%), Amoxicillin (49.6%), Ampicillin (47.6%), Clindamycin (47.2%) and Penicillin (40.6%). Among Gram positive mastitis bacteria higher mean in vitro resistance was observed in; Ampicillin (32.8%), Amoxicillin (32.6%), Penicillin (24.9%), Streptomycin (20.2%), Penicillinase Resistant Penicillin’s (15.4%) and Tetracycline (14.9%). More specifically, S. aurues exhibited high mean AMR against Penicillin (76.3%) and Ampicillin (70.3%) followed by Amoxicillin (45%), Streptomycin (40.6%), Tetracycline (24.5%) and Clindamycin (23.5%). E. coli showed high mean AMR to Erythromycin (78.7%), Tetracycline (51.5%), Ampicillin (49.25%), Amoxicillin (43.3%), Clindamycin (38.4%) and Penicillin (33.8%). Streptococcus spp. demonstrated higher (p =0.005) mean AMR against Kanamycin (> 20%) and full sensitivity (100%) to Clindamycin. Overall, mean Tetracycline (p = 0.013), Gentamycin (p = 0.001), Polymixin (p = 0.034), Erythromycin (p = 0.011) and Ampicillin (p = 0.009) resistance increased from the 2010’s than the 2000’s. Conclusion; the review indicated a rising AMR challenge among bovine mastitis bacteria in Ethiopia. Corresponding, public health implications demand a deeper, integrated investigation.

Keywords: antimicrobial resistance, dairy cattle, Ethiopia, Mastitis bacteria

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Authors: Anwar Beg, Sireetorn Kuharat, Rashid Mehmood, Rabil Tabassum, Meisam Babaie

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Nano-polymeric solar paints and sol-gels have emerged as a major new development in solar cell/collector coatings offering significant improvements in durability, anti-corrosion and thermal efficiency. They also exhibit substantial viscosity variation with temperature which can be exploited in solar collector designs. Modern manufacturing processes for such nano-rheological materials frequently employ stagnation flow dynamics under high temperature which invokes radiative heat transfer. Motivated by elaborating in further detail the nanoscale heat, mass and momentum characteristics of such sol gels, the present article presents a mathematical and computational study of the steady, two-dimensional, non-aligned thermo-fluid boundary layer transport of copper metal-doped water-based nano-polymeric sol gels under radiative heat flux. To simulate real nano-polymer boundary interface dynamics, thermal slip is analysed at the wall. A temperature-dependent viscosity is also considered. The Tiwari-Das nanofluid model is deployed which features a volume fraction for the nanoparticle concentration. This approach also features a Maxwell-Garnet model for the nanofluid thermal conductivity. The conservation equations for mass, normal and tangential momentum and energy (heat) are normalized via appropriate transformations to generate a multi-degree, ordinary differential, non-linear, coupled boundary value problem. Numerical solutions are obtained via the stable, efficient Runge-Kutta-Fehlberg scheme with shooting quadrature in MATLAB symbolic software. Validation of solutions is achieved with a Variational Iterative Method (VIM) utilizing Langrangian multipliers. The impact of key emerging dimensionless parameters i.e. obliqueness parameter, radiation-conduction Rosseland number (Rd), thermal slip parameter (α), viscosity parameter (m), nanoparticles volume fraction (ϕ) on non-dimensional normal and tangential velocity components, temperature, wall shear stress, local heat flux and streamline distributions is visualized graphically. Shear stress and temperature are boosted with increasing radiative effect whereas local heat flux is reduced. Increasing wall thermal slip parameter depletes temperatures. With greater volume fraction of copper nanoparticles temperature and thermal boundary layer thickness is elevated. Streamlines are found to be skewed markedly towards the left with positive obliqueness parameter.

Keywords: non-orthogonal stagnation-point heat transfer, solar nano-polymer coating, MATLAB numerical quadrature, Variational Iterative Method (VIM)

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Authors: Aman Johri, Sidhant Sood, Pooja Suresh

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This paper suggests a new and more efficient method of atomization of fuel in a combustor nozzle of a high bypass turbofan engine, using ultrasonic vibrations. Since atomization of fuel just before the fuel spray is injected into the combustion chamber is an important and crucial aspect related to functioning of a propulsion system, the technology suggested by this paper and the experimental analysis on the system components eventually proves to assist in complete and rapid combustion of the fuel in the combustor module of the engine. Current propulsion systems use carburetors, atomization nozzles and apertures in air intake pipes for atomization. The idea of this paper is to deploy new age hybrid technology, namely the Ultrasound Field Effect (UFE) to effectively atomize fuel before it enters the combustion chamber, as a viable and effective method to increase efficiency and improve upon existing designs. The Ultrasound Field Effect is applied axially, on diametrically opposite ends of an atomizer tube that gloves onto the combustor nozzle, where the fuel enters and exits under a pre-defined pressure. The Ultrasound energy vibrates the fuel particles to a breakup frequency. At reaching this frequency, the fuel particles start disintegrating into smaller diameter particles perpendicular to the axis of application of the field from the parent boundary layer of fuel flow over the baseplate. These broken up fuel droplets then undergo swirling effect as per the original nozzle design, with a higher breakup ratio than before. A significant reduction of the size of fuel particles eventually results in an increment in the propulsive efficiency of the engine. Moreover, the Ultrasound atomizer operates within a control frequency such that effects of overheating and induced vibrations are least felt on the overall performance of the engine. The design of an electrical manifold for the multiple-nozzle system over a typical can-annular combustor is developed along with this study, such that the product can be installed and removed easily for maintenance and repairing, can allow for easy access for inspections and transmits least amount of vibrational energy to the surface of the combustor. Since near-field ultrasound is used, the vibrations are easily controlled, thereby successfully reducing vibrations on the outer shell of the combustor. Experimental analysis is carried out on the effect of ultrasonic vibrations on flowing jet turbine fuel using an ultrasound generator probe and results of an effective decrease in droplet size across a constant diameter, away from the boundary layer of flow is noted using visual aid by observing under ultraviolet light. The choice of material for the Ultrasound inducer tube and crystal along with the operating range of temperatures, pressures, and frequencies of the Ultrasound field effect are also studied in this paper, while taking into account the losses incurred due to constant vibrations and thermal loads on the tube surface.

Keywords: atomization, ultrasound field effect, titanium mesh, breakup frequency, parent boundary layer, baseplate, propulsive efficiency, jet turbine fuel, induced vibrations

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Authors: Hsueh Ping Peng

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End-stage renal disease most commonly occurs in the elderly population. Elderly people are approaching the end of their lives, and when facing major life-threatening situations, apart from aggressive medical treatment, they can also choose treatment methods such as hospice care to improve their quality of life. The purpose of this study was to investigate factors associated with the awareness and willingness to sign hospice and palliative care consent forms in elderly with end-stage renal disease. This study used both quantitative, cross-sectional study designs. In the quantitative section, 110 elderly patients (aged 65 or above) with end-stage renal disease receiving conventional hemodialysis were recruited as study participants from a medical center in Taipei City. Data were collected using structured questionnaires. Study tools included basic demographic data, questionnaires on the awareness and perception of hospice and palliative care, etc. After collecting the data, data analysis was conducted using SPSS 20.0 statistical software, including descriptive statistics, chi-square test, logistic regression, and other inferential statistics. The results showed that the average age of participants was 71.6 years old, more males than females, average years of dialysis was 6.1 years and most subjects rated their self-perceived health status as fair. Results of the study are summarized as follows: Elderly people with end-stage renal disease did not have sufficient knowledge and awareness about hospice and palliative care. Influencing factors included level of education, marital status, years of dialysis and age, etc. Demographic factors influencing the signing of consent forms included gender, marital status, and age, which all showed significant impacts. Factors taken into consideration when signing consent forms included awareness of hospice care, understanding the relevant definitions of hospice care, and understanding that consent may be modified or cancelled at any time; it was predicted that people who knew more about ways to receive hospice care or more related definitions were more willing to sign the consent forms. In the qualitative study section, 10 participants who signed the consent form, five male, and 5 female, between the ages of 65-90, have completed the semi-structured interviews. Analysis of the interviews revealed six themes: (1) passing away peacefully, (2) autonomy on arrangements of life and death, (3) unwillingness to increase family and social burden, (4) friends and relatives’ experience influencing the decision to give consent, (5) sharing information to facilitate the giving of consent, (6) facing each day with ease, to reflect the experience and factors of consideration for elderly with end-stage renal disease when signing consent forms. The results of this study provides the awareness, thoughts and feelings of elderly with end-stage renal disease on signing consent forms, and serve as a future reference for the dialysis unit to enhance the promotion of hospice and palliative care and related caregiving measures, thereby improving the quality of life and care for elderly people with end-stage renal disease.

Keywords: end-stage renal disease, hemodialysis, hospice and palliative care, awareness, willingness

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Authors: Maryam Tabrizi, Shahrzad Aarup

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Objectives- Understanding the close association between oral health and overall health for older adults at the right time and right place, a person, focus treatment through Project ECHO telementoring. Methodology- Data from monthly ECHO telementoring sessions were provided for three years. Sessions including case presentations, overall health conditions, considering medications, organ functions limitations, including the level of cognition. Contributions- Providing the specialist level of providing care to all elderly regardless of their location and other health conditions and decreasing oral health inequity by increasing workforce via Project ECHO telementoring program worldwide. By 2030, the number of adults in the USA over the age of 65 will increase more than 60% (approx.46 million) and over 22 million (30%) of 74 million older Americans will need specialized geriatrician care. In 2025, a national shortage of medical geriatricians will be close to 27,000. Most individuals 65 and older do not receive oral health care due to lack of access, availability, or affordability. One of the main reasons is a significant shortage of Oral Health (OH) education and resources for the elderly, particularly in rural areas. Poor OH is a social stigma, a thread to quality and safety of overall health of the elderly with physical and cognitive decline. Poor OH conditions may be costly and sometimes life-threatening. Non-traumatic dental-related emergency department use in Texas alone was over $250 M in 2016. Most elderly over the age of 65 present with at least one or multiple chronic diseases such as arthritis, diabetes, heart diseases, and chronic obstructive pulmonary disease (COPD) are at higher risk to develop gum (periodontal) disease, yet they are less likely to get dental care. In addition, most older adults take both prescription and over-the-counter drugs; according to scientific studies, many of these medications cause dry mouth. Reduced saliva flow due to aging and medications may increase the risk of cavities and other oral conditions. Most dental schools have already increased geriatrics OH in their educational curriculums, but the aging population growth worldwide is faster than growing geriatrics dentists. However, without the use of advanced technology and creating a network between specialists and primary care providers, it is impossible to increase the workforce, provide equitable oral health to the elderly. Project ECHO is a guided practice model that revolutionizes health education and increases the workforce to provide best-practice specialty care and reduce health disparities. Training oral health providers for utilizing the Project ECHO model is a logical response to the shortage and increases oral health access to the elderly. Project ECHO trains general dentists & hygienists to provide specialty care services. This means more elderly can get the care they need, in the right place, at the right time, with better treatment outcomes and reduces costs.

Keywords: geriatric, oral health, project echo, chronic disease, oral health

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Authors: Enrico Gugliandolo, Salvatore Cuzzocrea, Rosalia Crupi

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Osteoarthritis (OA) is one of the most common chronic pain conditions in dogs and cats. OA pain is currently viewed as a mixed phenomenon involving both inflammatory and neuropathic mechanisms at the peripheral (joint) and central (spinal and supraspinal) levels. Oxidative stress has been implicated in OA pain. Although nonsteroidal anti-inflammatory drugs are commonly prescribed for OA pain, they should be used with caution in pets because of adverse effects in the long term and controversial efficacy on neuropathic pain. An unmet need remains for safe and effective long-term treatments for OA pain. Palmitoyl-glucosamine (PGA) is an analogue of the ALIAamide palmitoylethanolamide, i.e., a body’s own endocannabinoid-like compound playing a sentinel role in nociception. PGA, especially in the micronized formulation, was shown safe and effective in OA pain. The aim of this study was to investigate the effect of a co-micronized formulation of PGA with the natural antioxidant curcumin (PGA-cur) on OA pain. Ten Sprague-Dawley male rats were used for each treatment group. The University of Messina Review Board for the care and use of animals authorized the study. On day 0, rats were anesthetized (5.0% isoflurane in 100% O2) and received intra-articular injection of MIA (3 mg in 25 μl saline) in the right knee joint, with the left being injected an equal volume of saline. Starting the third day after MIA injection, treatments were administered orally three times per week for 21 days, at the following doses: PGA 20 mg/kg, curcumin 10 mg/kg, PGA-cur (2:1 ratio) 30 mg/kg. On day 0 and 3, 7, 14 and 21 days post-injection, mechanical allodynia was measured using a dynamic plantar Von Frey hair aesthesiometer and expressed as paw withdrawal threshold (PWT) and latency (PWL). Motor functional recovery of the rear limb was evaluated on the same time points by walking track analysis using the sciatic functional index. On day 21 post-MIA injection, the concentration of the following inflammatory and nociceptive mediators was measured in serum using commercial ELISA kits: tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), nerve growth factor (NGF) and matrix metalloproteinase-1-3-9 (MMP-1, MMP-3, MMP-9). The results were analyzed by ANOVA followed by Bonferroni post-hoc test for multiple comparisons. Micronized PGA reduced neuropathic pain, as shown by the significant higher PWT and PWL values compared to vehicle group (p < 0.0001 for all the evaluated time points). The effect of PGA-cur was superior at all time points (p < 0.005). PGA-cur restored motor function already on day 14 (p < 0.005), while micronized PGA was effective a week later (D21). MIA-induced increase in the serum levels of all the investigated mediators was inhibited by PGA-cur (p < 0.01). PGA was also effective, except on IL-1 and MMP-3. Curcumin alone was inactive in all the experiments at any time point. The encouraging results suggest that PGA-cur may represent a valuable option in OA pain management and warrant further confirmation in well-powered clinical trials.

Keywords: ALIAmides, curcumin, osteoarthritis, palmitoyl-glucosamine

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Authors: Nanadcha Sinjindawong

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This article discusses the design process of a community mall called Castle of The Mall-dern. The concept behind this mall is to combine elements of a medieval castle with modern architecture. The author aims to create a building that fits into the surroundings while also providing users with the vibes of the ancient era. The total area used for the mall is 4,000 square meters, with three floors. The first floor is 1,500 square meters, the second floor is 1,750 square meters, and the third floor is 750 square meters. Research Aim: The aim of this research is to design a community mall that sells ancient clothes and accessories, and to combine sustainable architectural design with the ideas of ancient architecture in an urban area with convenient transportation. Methodology: The research utilizes qualitative research methods in architectural design. The process begins with calculating the given area and dividing it into different zones. The author then sketches and draws the plan of each floor, adding the necessary rooms based on the floor areas mentioned earlier. The program "SketchUp" is used to create an online 3D model of the community mall, and a physical model is built for presentation purposes on A1 paper, explaining all the details. Findings: The result of this research is a community mall with various amenities. The first floor includes retail shops, clothing stores, a food center, and a service zone. Additionally, there is an indoor garden with a fountain and a tree for relaxation. The second and third floors feature a void in the middle, with a few stores, cafes, restaurants, and studios on the second floor. The third floor is home to the administration and security control room, as well as a community gathering area designed as a public library with a café inside. Theoretical Importance: This research contributes to the field of sustainable architectural design by combining ancient architectural ideas with modern elements. It showcases the potential for creating buildings that blend historical aesthetics with contemporary functionality. Data Collection and Analysis Procedures: The data for this research is collected through a combination of area calculation, sketching, and building a 3D model. The analysis involves evaluating the design based on the allocated area, zoning, and functional requirements for a community mall. Question Addressed: The research addresses the question of how to design a community mall with a theme of ancient Medieval and Victorian eras. It explores how to combine sustainable architectural design principles with historical aesthetics to create a functional and visually appealing space. Conclusion: In conclusion, this research successfully designs a community mall called “Castle of The Mall-dern” that incorporates elements of Medieval and Victorian architecture. The building encompasses various zones, including retail shops, restaurants, community gathering areas, and service zones. It also features an interior garden and a public library within the mall. The research contributes to the field of sustainable architectural design by showcasing the potential for combining ancient architectural ideas with modern elements in an urban setting.

Keywords: 3D model, community mall, modern architecture, medieval architecture

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Authors: Uraib Sharaha, Ahmad Salman, Eladio Rodriguez-Diaz, Elad Shufan, Klaris Riesenberg, Irving J. Bigio, Mahmoud Huleihel

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Antimicrobial drugs have played an indispensable role in controlling illness and death associated with infectious diseases in animals and humans. However, the increasing resistance of bacteria to a broad spectrum of commonly used antibiotics has become a global healthcare problem. Many antibiotics had lost their effectiveness since the beginning of the antibiotic era because many bacteria have adapted defenses against these antibiotics. Rapid determination of antimicrobial susceptibility of a clinical isolate is often crucial for the optimal antimicrobial therapy of infected patients and in many cases can save lives. The conventional methods for susceptibility testing require the isolation of the pathogen from a clinical specimen by culturing on the appropriate media (this culturing stage lasts 24 h-first culturing). Then, chosen colonies are grown on media containing antibiotic(s), using micro-diffusion discs (second culturing time is also 24 h) in order to determine its bacterial susceptibility. Other methods, genotyping methods, E-test and automated methods were also developed for testing antimicrobial susceptibility. Most of these methods are expensive and time-consuming. Fourier transform infrared (FTIR) microscopy is rapid, safe, effective and low cost method that was widely and successfully used in different studies for the identification of various biological samples including bacteria; nonetheless, its true potential in routine clinical diagnosis has not yet been established. The new modern infrared (IR) spectrometers with high spectral resolution enable measuring unprecedented biochemical information from cells at the molecular level. Moreover, the development of new bioinformatics analyses combined with IR spectroscopy becomes a powerful technique, which enables the detection of structural changes associated with resistivity. The main goal of this study is to evaluate the potential of the FTIR microscopy in tandem with machine learning algorithms for rapid and reliable identification of bacterial susceptibility to antibiotics in time span of few minutes. The UTI E.coli bacterial samples, which were identified at the species level by MALDI-TOF and examined for their susceptibility by the routine assay (micro-diffusion discs), are obtained from the bacteriology laboratories in Soroka University Medical Center (SUMC). These samples were examined by FTIR microscopy and analyzed by advanced statistical methods. Our results, based on 700 E.coli samples, were promising and showed that by using infrared spectroscopic technique together with multivariate analysis, it is possible to classify the tested bacteria into sensitive and resistant with success rate higher than 90% for eight different antibiotics. Based on these preliminary results, it is worthwhile to continue developing the FTIR microscopy technique as a rapid and reliable method for identification antibiotic susceptibility.

Keywords: antibiotics, E.coli, FTIR, multivariate analysis, susceptibility, UTI

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Authors: Jabulani Gilford Kheswa, Thembelihle Lobi

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From a cultural perspective, expression of hegemonic masculinity in South Africa continues to escalate among adolescent males who grow up in communities lacking in role models and recreational facilities. However, when the schools are constructive, and peer influence is positive, adolescent male can potentially express character strengths and lead a meaningful life. Drawing from Bronfenbrenner’s Ecological Model and Keyes and Ryff’s six dimensions of psychological well-being and mental health, such youth may exemplify positive self-esteem, problem- focused coping strategies, condom self-efficacy, good leadership skills, enhanced motivation and a positive emotional state, which buffer against risky sexual behaviors. This paper was aimed at investigating the relationships between adolescent males’ sexual behavior and psychological well-being. This study employed a quantitative research to collect data from 54 Xhosa-speaking adolescent males from one school high school in Fort Beaufort, Eastern Cape, South Africa. These learners were from grade nine, ten and eleven with their ages ranging from 14 to 20. Prior the research commenced, the school principal and caregivers of the learners who participated in the study, gave their informed consent. Self- administered closed-ended questionnaire with Section A (that is, biographical information) and Section B with each question rated on the 5–point Likert scale was used. The advantages of questionnaires include a high response rate as they require less time and offer anonymity because participants’ names are not identified. The SPSS version 18 was used for statistical data analysis. The mean age was 16.83 with a standard deviation of 1.611. 44.4% of the participants were from grade 9, 33.3% from grade 10 and 22.2% from grade 11. The Chronbach alpha of 0.79 was yielded, with respect to self- esteem of adolescent males. In this study, 76.9% reported to attend church services whilst 23% indicated not to attend church services. A further 96.2% of adolescent males indicated to have good relations with guardians while only 3.8% had poorer relations. A large proportion of adolescent males (72.9%) indicated to high-quality friendship as opposed to 27.1% who reported being receiving negative guidance from peers. Other findings revealed that 81.1% of the participants’ parents do not drink alcohol, and they cope at school as 79.6% reported protective factors as attributable towards non-engagement to risky sexual practices. As a result, 81.4% of participants reported not to participate in criminal activities although 85% of the participants indicated that in their school there are drugs. It could be speculated from this study that adolescent males whose caregivers are authoritative, find purpose in life and are most likely to be socially and academically competent. This paper leads to further research interest into mental health, coping strategies and sexual decision-making skills of the youth in South Africa.

Keywords: church, mental health, school, sexual behaviour

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Authors: Jie Lin, Yiwen Pan, Li Zhang, Zhangyong Xia

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Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids, immune cells, and extracellular matrix in the arterial walls. This pathological process can lead to the formation of plaques that can obstruct blood flow and trigger various cardiovascular diseases such as heart attack and stroke. The underlying molecular mechanisms still remain unclear, although many studies revealed the dysfunction of endothelial cells, recruitment and activation of monocytes and macrophages, and the production of pro-inflammatory cytokines and chemokines in atherosclerosis. This study aimed to identify hub genes involved in the progression of atherosclerosis and to analyze their biological function in silico, thereby enhancing our understanding of the disease’s molecular mechanisms. Through the analysis of microarray data, we examined the gene expression in media and neo-intima from plaques, as well as distant macroscopically intact tissue, across a cohort of 32 hypertensive patients. Initially, 112 differentially expressed genes (DEGs) were identified. Subsequent immune infiltration analysis indicated a predominant presence of 27 immune cell types in the atherosclerosis group, particularly noting an increase in monocytes and macrophages. In the Weighted gene co-expression network analysis (WGCNA), 10 modules with a minimum of 30 genes were defined as key modules, with blue, dark, Oliver green and sky-blue modules being the most significant. These modules corresponded respectively to monocyte, activated B cell, and activated CD4 T cell gene patterns, revealing a strong morphological-genetic correlation. From these three gene patterns (modules morphology), a total of 2509 key genes (Gene Significance >0.2, module membership>0.8) were extracted. Six hub genes (CD36, DPP4, HMOX1, PLA2G7, PLN2, and ACADL) were then identified by intersecting 2509 key genes, 102 DEGs with lipid-related genes from the Genecard database. The bio-functional analysis of six hub genes was estimated by a robust classifier with an area under the curve (AUC) of 0.873 in the ROC plot, indicating excellent efficacy in differentiating between the disease and control group. Moreover, PCA visualization demonstrated clear separation between the groups based on these six hub genes, suggesting their potential utility as classification features in predictive models. Protein-protein interaction (PPI) analysis highlighted DPP4 as the most interconnected gene. Within the constructed key gene-drug network, 462 drugs were predicted, with ursodeoxycholic acid (UDCA) being identified as a potential therapeutic agent for modulating DPP4 expression. In summary, our study identified critical hub genes implicated in the progression of atherosclerosis through comprehensive bioinformatic analyses. These findings not only advance our understanding of the disease but also pave the way for applying similar analytical frameworks and predictive models to other diseases, thereby broadening the potential for clinical applications and therapeutic discoveries.

Keywords: atherosclerosis, hub genes, drug prediction, bioinformatics

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