Search results for: self efficacy

Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy

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The drug discovery and development process is generally known to be a very lengthy and labor-intensive process. Therefore, in order to be able to deliver prompt and effective responses to cure certain diseases, there is an urgent need to reduce the time and resources needed to design, develop, and optimize potential drugs. Computer-aided drug design (CADD) is able to alleviate this issue by applying computational power in order to streamline the whole drug discovery process, starting from target identification to lead optimization. This drug design approach can be predominantly applied to diseases that cause major public health concerns, such as tuberculosis. Hitherto, there has been no concrete cure for this disease, especially with the continuing emergence of drug resistant strains. In this study, CADD is employed for tuberculosis by first identifying a key enzyme in the mycobacterium’s metabolic pathway that would make a good drug target. One such potential target is the lipoate protein ligase B enzyme (LipB), which is a key enzyme in the M. tuberculosis metabolic pathway involved in the biosynthesis of the lipoic acid cofactor. Its expression is considerably up-regulated in patients with multi-drug resistant tuberculosis (MDR-TB) and it has no known back-up mechanism that can take over its function when inhibited, making it an extremely attractive target. Using cutting-edge computational methods, compounds from AnalytiCon Discovery Natural Derivatives database were screened and docked against the LipB enzyme in order to rank them based on their binding affinities. Compounds which have better binding affinities than LipB’s known inhibitor, decanoic acid, were subjected to in silico toxicity evaluation using the ADMET and TOPKAT protocols. Out of the 31,692 compounds in the database, 112 of these showed better binding energies than decanoic acid. Furthermore, 12 out of the 112 compounds showed highly promising ADMET and TOPKAT properties. Future studies involving in vitro or in vivo bioassays may be done to further confirm the therapeutic efficacy of these 12 compounds, which eventually may then lead to a novel class of anti-tuberculosis drugs.

Keywords: pharmacophore, molecular docking, lipoate protein ligase B (LipB), ADMET, TOPKAT

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Authors: Hansraj Riteesh Bookun, Cassandra Monique Hidajat

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This pilot study investigated the efficacy of a newly designed shoe which will act as an intermittent pneumatic compression device to augment venous flow in the lower limb. The aim was to assess the degree with which a wearable intermittent compression device can increase the venous flow in the popliteal vein. Background: Deep venous thrombosis and chronic venous insufficiency are relatively common problems with significant morbidity and mortality. While mechanical and chemical thromboprophylaxis measures are in place in hospital environments (in the form of TED stockings, intermittent pneumatic compression devices, analgesia, antiplatelet and anticoagulant agents), there are limited options in a community setting. Additionally, many individuals are poorly tolerant of graduated compression stockings due to the difficulty in putting them on, their constant tightness and increased associated discomfort in warm weather. These factors may hinder the management of their chronic venous insufficiency. Method: The device is lightweight, easy to wear and comfortable, with a self-contained power source. It features a Bluetooth transmitter and can be controlled with a smartphone. It is externally almost indistinguishable from a normal shoe. During activation, two bladders are inflated -one overlying the metatarsal heads and the second at the pedal arch. The resulting cyclical increase in pressure squeezes blood into the deep venous system. This will decrease periods of stasis and potentially reduce the risk of deep venous thrombosis. The shoe was fitted to 2 healthy participants and the peak systolic velocity of flow in the popliteal vein was measured during and prior to intermittent compression phases. Assessments of total flow volume were also performed. All haemodynamic assessments were performed with ultrasound by a licensed sonographer. Results: Mean peak systolic velocity of 3.5 cm/s with standard deviation of 1.3 cm/s were obtained. There was a three fold increase in mean peak systolic velocity and five fold increase in total flow volume. Conclusion: The device augments venous flow in the leg significantly. This may contribute to lowered thromboembolic risk during periods of prolonged travel or immobility. This device may also serve as an adjunct in the treatment of chronic venous insufficiency. The study will be replicated on a larger scale in a multi—centre trial.

Keywords: venous, intermittent compression, shoe, wearable device

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Authors: Maryam Shayani Rad, Seyed Ahmad Mohajeri, Mohsen Mouhebati, Seyed Danial Mousavi

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High blood pressure is one of the most important and serious health-threatening because of no symptoms in most people, which can lead to sudden heart attack, heart failure, and stroke. Nowadays, herbal medicine is one of the best and safest strategies for treatment that have no adverse effects. Apium graveolens (celery) can be used as an alternative treatment for many health conditions such as hypertension. Natural compounds reduce blood pressure via different mechanisms in which Apium graveolens extract provides potent calcium channel blocking properties. A randomized, double-blind, placebo-controlled, cross-over clinical trial was done to evaluate the efficacy of formulated Apium graveolens extract with a maximum yield of 3-n-butylphthalide to reduce systolic and diastolic blood pressure in patients with hypertension. 54 hypertensive patients in the range of 20-68 years old were randomly assigned to the treatment group (26 cases) and the placebo control group (26 cases) and were crossed over after washout duration. The treatment group received at least 2 grams of formulated powder in hard capsules orally, before each meal, 2 times daily. The control group received 2 grams of placebo in hard capsules orally, exactly as the same as shape, time, and doses of treatment group. Treatment was administrated in 12 weeks with 4 weeks washout period at the middle of the study, meaning 4 weeks drug consumption for the treatment group, 4 weeks washout and 4 weeks placebo consumption, and vice versa for the placebo control group. The clinical assessment was done 4 times, including at the beginning and ending of the drug and placebo consumption period by 24-hour ambulatory blood pressure monitoring (ABPM) holter, which measured blood pressure every 15 minutes continuously. There was a statistically significant decrease in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the end of drug duration compared to baseline. The changes after 4 weeks on average was about 12.34 mm Hg for the SBP (P < 0.005) and 7.83 mm Hg for the DBP (P < 0.005). The results from this clinical trial study showed this Apium graveolens extract formulation in the mentioned dosage had a significant effect on blood pressure-lowering for hypertensive patients.

Keywords: Apium graveolens extract, clinical trial, cross-over, hypertension

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Authors: Rema Vazhappilly, Tapas Das

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Oleic acid is a cis unsaturated fatty acid and is known to be a partially essential fatty acid due to its limited endogenous synthesis during pregnancy and lactation. Previous studies have demonstrated the role of oleic acid in neuronal differentiation and brain phospholipid synthesis. These evidences indicate a major role for oleic acid in learning and memory. Interestingly, oleic acid has been shown to enhance hippocampal long term potentiation (LTP), the physiological correlate of long term synaptic plasticity. However the effect of oleic acid on short term synaptic plasticity has not been investigated. Short term potentiation (STP) is the physiological correlate of short term synaptic plasticity which is the key underlying molecular mechanism of short term memory and neuronal information processing. STP in the hippocampal CA1 region has been known to require the activation of N-methyl-D-aspartate receptors (NMDARs). The NMDAR dependent hippocampal STP as a potential mechanism for short term memory has been a subject of intense interest for the past few years. Therefore in the present study the effect of oleic acid on NMDAR dependent hippocampal STP was determined in mouse hippocampal slices (in vitro) using Multi-electrode array system. STP was induced by weak tetanic Stimulation (one train of 100 Hz stimulations for 0.1s) of the Schaffer collaterals of CA1 region of the hippocampus in slices treated with different concentrations of oleic acid in presence or absence of NMDAR antagonist D-AP5 (30 µM) . Oleic acid at 20 (mean increase in fEPSP amplitude = ~135 % Vs. Control = 100%; P<0.001) and 30 µM (mean increase in fEPSP amplitude = ~ 280% Vs. Control = 100%); P<0.001) significantly enhanced the STP following weak tetanic stimulation. Lower oleic acid concentrations at 10 µM did not modify the hippocampal STP induced by weak tetanic stimulation. The hippocampal STP induced by weak tetanic stimulation was completely blocked by the NMDA receptor antagonist D-AP5 (30µM) in both oleic acid and control treated hippocampal slices. This lead to the conclusion that the hippocampal STP elicited by weak tetanic stimulation and enhanced by oleic acid was NMDAR dependent. Together these findings suggest that oleic acid may enhance the short term memory and neuronal information processing through the modulation of NMDAR dependent hippocampal short-term synaptic plasticity. In conclusion this study suggests the possible role of oleic acid to prevent the short term memory loss and impaired neuronal function throughout development.

Keywords: oleic acid, short-term potentiation, memory, field excitatory post synaptic potentials, NMDA receptor

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Authors: Mokgadi Miranda Hlongwane, Ntebogeng Sharon Mokgalaka, Felix Dapare Dakora

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Lessertia (L.) frutescens (syn. Sutherlandia frutescens) is a leguminous medicinal plant indigenous to South Africa. Traditionally, L. frutescens has been used to treat cancer, diabetes, epilepsy, fever, HIV, stomach problems, wounds and other ailments. This legume is endemic to the Cape fynbos, with large populations occurring wild and cultivated in the Cape Florist Region. Its widespread distribution in the Western Cape, Northern Cape, Eastern Cape and Kwazulu-Natal is linked to its increased use as a phytomedicine in the treatment of various diseases by traditional healers. The frequent harvesting of field plants for use as a medicine has made it necessary to undertake studies towards the conservation of Lessertia frutescens. As a legume, this species can form root nodules and fix atmospheric N₂ when in symbiosis with soil bacteria called rhizobia. So far, however, few studies (if any) have been done on the efficacy and diversity of native bacterial symbionts nodulating L. frutescens in South Africa. The aim of this project was to isolate and characterize L. frutescens-nodulating bacteria from five different locations in the Western Cape Province. This was done by trapping soil rhizobia using rhizosphere soil suspension to inoculate L. frutescens seedlings growing in sterilized sand and receiving sterile N-free Hoagland nutrient solution under glasshouse conditions. At 60 days after planting, root nodules were harvested from L. frutescens plants, surface-sterilized, macerated, and streaked on yeast mannitol agar (YMA) plates and incubated at 28 ˚C for observation of bacterial growth. The majority of isolates were slow-growers that took 6-14 days to appear on YMA plates. However, seven isolates were fast-growers, taking 2-4 days to appear on YMA plates. Single-colony cultures of the isolates were assessed for their ability to nodulate L. frutescens as a homologous host under glasshouse conditions. Of the 92 bacterial isolates tested, 63 elicited nodule formation on L. frutescens. Symbiotic effectiveness varied markedly between and among test isolates. There were also significant (p≤0.005) differences in nodulation, shoot biomass, photosynthetic rates, leaf transpiration and stomatal conductance of L. frutescens plants inoculated with the test isolates, which is an indication of their functional diversity.

Keywords: lessertia frutescens, nodulating, rhizobia, symbiotic effectiveness

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Authors: Shokooh Moghadam, Mohammad Taghi Khorasani, Sajjad Seifi Mofarah, M. Daliri

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Through the recent two decades, the use of magnetic-property materials with the aim of target cell’s separation and eventually cancer treatment has incredibly increased. Numerous factors can alter the efficacy of this method on curing. In this project, the effect of magnetic field on adhesion of PDL and L929 cells on nanocomposite of iron oxide/PHB with different density of iron oxides (1%, 2.5%, 5%) has been studied. The nanocamposite mentioned includes a polymeric film of poly hydroxyl butyrate and γ-Fe2O3 particles with the average size of 25 nanometer dispersed in it and during this process, poly vinyl alcohol with 98% hydrolyzed and 78000 molecular weight was used as an emulsion to achieve uniform distribution. In order to get the homogenous film, the solution of PHB and iron oxide nanoparticles were put in a dry freezer and in liquid nitrogen, which resulted in a uniform porous scaffold and for removing porosities a 100◦C press was used. After the synthesis of a desirable nanocomposite film, many different tests were performed, First, the particles size and their distribution in the film were evaluated by transmission electron microscopy (TEM) and even FTIR analysis and DMTA test were run in order to observe and accredit the chemical connections and mechanical properties of nanocomposites respectively. By comparing the graphs of case and control samples, it was established that adding nano particles caused an increase in crystallization temperature and the more density of γ-Fe2O3 lead to more Tg (glass temperature). Furthermore, its dispersion range and dumping property of samples were raised up. Moreover, the toxicity, morphologic changes and adhesion of fibroblast and cancer cells were evaluated by a variety of tests. All samples were grown in different density and in contact with cells for 24 and 48 hours within the magnetic fields of 2×10^-3 Tesla. After 48 hours, the samples were photographed with an optic and SEM and no sign of toxicity was traced. The number of cancer cells in the case of sample group was fairly more than the control group. However, there are many gaps and unclear aspects to use magnetic field and their effects in cancer and all diseases treatments yet to be discovered, not to neglect that there have been prominent step on this way in these recent years and we hope this project can be at least a minimum movement in this issue.

Keywords: nanocomposite, cell attachment, magnetic field, cytotoxicity

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Authors: Zhang Tao, Si Tang, Zhang Yufeng, Jin Jiahua

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Work pressure is an emerging research of organizational behavior. Many factors associated with this study also attracted the interest of scholars. Macao is surrounding by open micro-capitalist economy which has a high internationalization level and Mature operation system. And there is no doubt that tourism and hotel service industry is the pillar of the Macao economy with the developing of the mainland individual tourist visa. More and more cities are willing to inclusive culture diversity which lead to the amount of inbound tourists present high-speed up trend cause the hotel industry has a strong customer base and development space. At the same time, the hotel staff is an important role in the service. However, affected by some adverse factors, the hotel staff face a variety of pressures. This study combs the concept and theory of pressures relevant influencing factors and puts forward the purpose of this research. The focus of this study will be organizational supported by work efficiency and work pressure, using qualitative and quantitative research methods. Through questionnaires and interviews, 10 hotels in Macao were selected and 500 questionnaires were distributed to the employees. Statistical analysis software SPSS was used for descriptive statistics. By exploratory factor analysis and confirmatory factor analysis, effect. And the relevant practitioners on behalf of the interview content analysis. The innovation of this research lies in the empirical study of the relationship between the working pressure, organizational support and working efficiency of Macau hotel practitioners, and constructs and validates the structural model of the relationship among them. This model will be helpful for people to use more research methods to study hotel practitioners pressure in the future. At the same time, we can draw the following conclusions: 1. There is a significant negative correlation between salary level and job stress; 2. There is a significant negative correlation between job stress and performance; 3. Different organizational support can interfere the relationship between job stress and performance; 4. Put forward the strategy of relevance adjustment, which provides a reference value for the hotel industry in human resource management. It would be helpful to improve their service standard by training their practitioners more scientifically and rationally.

Keywords: Macau, perceived organizational support, work stress, work efficiency

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Authors: Hannah O'Sullivan, Esther Quinn

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Purpose: The Architectural, Engineering, and Construction (AEC) industry has historically struggled to adapt to change. Although the ability to innovate and successfully implement organizational change has been demonstrated to be critical in achieving a sustainable competitive advantage in the industry, many AEC organizations continue to struggle when affecting organizational change. One prominent area of organizational change that presents many challenges in the industry is the adoption of new forms of technology, for example, Building Information Modelling (BIM). Certain Organisational Change Management (OCM) practices have been proven to be effective in supporting organizations to adopt change, but little research has been carried out on diverging employee attitudes to change relative to their roles within the organization. The purpose of this research study is to examine how OCM practices influence employee attitudes to change when adopting new forms of technology and to analyze the diverging employee perspectives within an organization on the importance of different OCM strategies. Methodology: Adopting an interview-based approach, a case study was carried out on a large-sized, prominent Irish construction organization who are currently adopting a new technology platform for its projects. Qualitative methods were used to gain insight into differing perspectives on the utilization of various OCM practices and their efficacy when adopting a new form of technology on projects. Change agents implementing the organizational change gave insight into their intentions with the technology rollout strategy, while other employees were interviewed to understand how this rollout strategy was received and the challenges that were encountered. Findings: The results of this research study are currently being finalized. However, it is expected that employees in different roles will value different OCM practices above others. Findings and conclusions will be determined within the coming weeks. Value: This study will contribute to the body of knowledge relating to the introduction of new technologies, including BIM, to AEC organizations. It will also contribute to the field of organizational change management, providing insight into methods of introducing change that will be most effective for different employees based on their roles and levels of experience within the industry. The focus of this study steers away from traditional studies of the barriers to adopting BIM in its first instance at an organizational level and centers on the direct effect on employees when a company changes the technology platform being used.

Keywords: architectural, engineering, and construction (AEC) industry, Building Information Modelling, case study, challenges, employee perspectives, organisational change management.

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Authors: M. M. Essa, S. Subash, M. Akbar, S. Al-Adawi, A. Al-Asmi, G. J. Guillemein

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Objective: Transgenic (tg) mice which contain an amyloid precursor protein (APP) gene mutation, develop extracellular amyloid beta (Aβ) deposition in the brain, and severe memory and behavioural deficits with age. These mice serve as an important animal model for testing the efficacy of novel drug candidates for the treatment and management of symptoms of Alzheimer's disease (AD). Several reports have suggested that oxidative stress is the underlying cause of Aβ neurotoxicity in AD. Pomegranates contain very high levels of antioxidants and several medicinal properties that may be useful for improving the quality of life in AD patients. In this study, we investigated the effect of dietary supplementation of Omani pomegranate extract on the memory, anxiety and learning skills along with inflammation in an AD mouse model containing the double Swedish APP mutation (APPsw/Tg2576). Methods: The experimental groups of APP-transgenic mice from the age of 4 months were fed custom-mix diets (pellets) containing 4% pomegranate. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4-5 months and 18-19 months using the Morris water maze test, rota rod test, elevated plus maze test, and open field test. Further, inflammatory parameters also analysed. Results: APPsw/Tg2576 mice that were fed a standard chow diet without pomegranates showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination along with increased inflammation compared to the wild type mice on the same diet, at the age of 18-19 months In contrast, APPsw/Tg2576 mice that were fed a diet containing 4% pomegranates showed a significant improvements in memory, learning, locomotor function, and anxiety with reduced inflammatory markers compared to APPsw/Tg2576 mice fed the standard chow diet. Conclusion: Our results suggest that dietary supplementation with pomegranates may slow the progression of cognitive and behavioural impairments in AD. The exact mechanism is still unclear and further extensive research needed.

Keywords: Alzheimer's disease, pomegranates, oman, cognitive decline, memory loss, anxiety, inflammation

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Authors: Hassan Karimi, Fred Piercy, Ruoxi Chen, Ana L. Jaramillo-Sierra, Wei-Ning Chang, Manjushree Palit, Catherine Martosudarmo, Angelito Antonio

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Background: The two psychotherapy camps, the randomized clinical trials (RCTs) and the common factors model, have competitively claimed specific explanations for therapy effectiveness. Recently, scholars called for empirical evidence to show the role of common factors in therapeutic outcome in marriage and family therapy. Purpose: This cross-national study aims to explore how clinicians, across different nations and theoretical orientations, attribute the contribution of common factors to therapy outcome. Method: A brief common factors questionnaire (CFQ-with a Cronbach’s Alpha, 0.77) was developed and administered in seven nations. A series of statistical analyses (paired-samples t-test, independent sample t-test, ANOVA) were conducted: to compare clinicians perceived contribution of total common factors versus model-specific factors, to compare each pair of common factors’ categories, and to compare clinicians from collectivistic nations versus clinicians from individualistic nation. Results: Clinicians across seven nations attributed 86% to common factors versus 14% to model-specific factors. Clinicians attributed 34% of therapeutic change to client’s factors, 26% to therapist’s factors, 26% to relationship factors, and 14% to model-specific techniques. The ANOVA test indicated each of the three categories of common factors (client 34%, therapist 26%, relationship 26%) showed higher contribution in therapeutic outcome than the category of model specific factors (techniques 14%). Clinicians with psychology degree attributed more contribution to model-specific factors than clinicians with MFT and counseling degrees who attributed more contribution to client factors. Clinicians from collectivistic nations attributed larger contributions to therapist’s factors (M=28.96, SD=12.75) than the US clinicians (M=23.22, SD=7.73). The US clinicians attributed a larger contribution to client’s factors (M=39.02, SD=1504) than clinicians from the collectivistic nations (M=28.71, SD=15.74). Conclusion: The findings indicate clinicians across the globe attributed more than two thirds of therapeutic change to CFs, which emphasize the training of the common factors model in the field. CFs, like model-specific factors, vary in their contribution to therapy outcome in relation to specific client, therapist, problem, treatment model, and sociocultural context. Sociocultural expectations and norms should be considered as a context in which both CFs and model-specific factors function toward therapeutic goals. Clinicians need to foster a cultural competency specifically regarding the divergent ways that CFs can be activated due to specific sociocultural values.

Keywords: common factors, model-specific factors, cross-national survey, therapist cultural competency, enhancing therapist efficacy

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Authors: Neerja Bharti, Drishya P.

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Introduction: Thyroidectomies are extensive surgeries involving a significant degree of tissue handling and dissection and are associated with considerable postoperative pain. Regional anaesthesia techniques have immerged as possible inexpensive and safe alternatives to opioids in the management of pain after thyroidectomy. The front of the neck is innervated by branches from the cervical plexus, and hence, several approaches for superficial and deep cervical plexus block (CPB) have been described to provide postoperative analgesia after neck surgery. However, very few studies have explored the analgesic efficacy of intermediate CPB for thyroid surgery. In this study, we have evaluated the effects of ultrasound-guided bilateral intermediate CPB on perioperative opioid consumption in patients undergoing thyroidectomy under general anesthesia. Methods: In this prospective randomized controlled study, fifty ASA grade I-II adult patients undergoing thyroidectomy were randomly divided into two groups: the study group received ultrasound-guided bilateral intermediate CPB with 10 ml 0.5% ropivacaine on each side, while the control group received the same block with 10 ml normal saline on each side just after induction of anesthesia. Anesthesia was induced with propofol, fentanyl, and vecuronium and maintained with propofol infusion titrated to maintain the BIS between 40 and 60. During the postoperative period, rescue analgesia was provided with PCA fentanyl, and the pain scores, total fentanyl consumption, and incidence of nausea and vomiting during 24 hours were recorded, and overall patient satisfaction was assessed. Results: The groups were well-matched with respect to age, gender, BMI, and duration of surgery. The difference in intraoperative propofol and fentanyl consumption was not statistically significant between groups. However, the intraoperative haemodynamic parameters were better maintained in the study group than in the control group. The postoperative pain scores, as measured by VAS at rest and during movement, were lower, and the total fentanyl consumption during 24 hours was significantly less in the study group as compared to the control group. Patients in the study group reported better satisfaction scores than those in the control group. No adverse effects of ultrasound-guided intermediate CPB block were reported. Conclusion: We concluded that ultrasound-guided intermediate cervical plexus block is a safe and effective method for providing perioperative analgesia during thyroid surgery.

Keywords: thyroidectomy, cervical plexus block, pain relief, opioid consumption

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Authors: Masahiro Takimoto

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The present study explored how the metaphor awareness-raising approach affects the involvement of the right hemisphere in developing EFL learners’ knowledge regarding the different degrees of politeness embedded within different request expressions. The present study was motivated by theoretical considerations regarding the conceptual projection and the metaphorical idea of politeness is distance, as proposed; this study applied these considerations to develop Japanese learners’ knowledge regarding the different politeness degrees and to explore the connection between the metaphorical concept projection and right-hemisphere dominance. Japanese EFL learners do not know certain language strategies (e.g., English requests can be mitigated with biclausal downgraders, including the if-clause with past-tense modal verbs) and have difficulty adjusting the politeness degrees attached to request expressions according to situations. The present study used a pre/post-test design to reaffirm the efficacy of the cognitive technique and its connection to right-hemisphere involvement by mouth asymmetry technique. Mouth asymmetry measurement has been utilized because speech articulation, normally controlled mainly by one side of the brain, causes muscles on the opposite side of the mouth to move more during speech production. The present research did not administer the delayed post-test because it emphasized determining whether metaphor awareness-raising approaches for developing EFL learners’ pragmatic proficiency entailed right-hemisphere activation. Each test contained an acceptability judgment test (AJT) along with a speaking test in the post-test. The study results show that the metaphor awareness-raising group performed significantly better than the control group with regard to acceptability judgment and speaking tests post-test. These data revealed that the metaphor awareness-raising approach could promote L2 learning because it aided input enhancement and concept projection; through these aspects, the participants were able to comprehend an abstract concept: the degree of politeness in terms of the spatial concept of distance. Accordingly, the proximal-distal metaphor enabled the study participants to connect the newly spatio-visualized concept of distance to the different politeness degrees attached to different request expressions; furthermore, they could recall them with the left side of the mouth being wider than the right. This supported certain findings from previous studies that indicated the possible involvement of the brain's right hemisphere in metaphor processing.

Keywords: metaphor awareness-raising, right hemisphere, L2 politeness, mouth asymmetry

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Authors: Syed Asif Hassan, Tabrej Khan

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Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder, of the central nervous system (CNS). In the present scenario, the current therapies either do not halt the progression of the disease or have side effects which limit the usage of current Disease Modifying Therapies (DMTs) for a longer period of time. Therefore, keeping the current treatment failure schema, we are focusing on screening novel analogues of the available DMTs that specifically bind and inhibit the Sphingosine1-phosphate receptor1 (S1PR1) thereby hindering the lymphocyte propagation toward CNS. The novel drug-like analogs molecule will decrease the frequency of relapses (recurrence of the symptoms associated with MS) with higher efficacy and lower toxicity to human system. In this study, an integrated approach involving ligand-based virtual screening protocol (Ultrafast Shape Recognition with CREDO Atom Types (USRCAT)) to identify the non-toxic drug like analogs of the approved DMTs were employed. The potency of the drug-like analog molecules to cross the Blood Brain Barrier (BBB) was estimated. Besides, molecular docking and simulation using Auto Dock Vina 1.1.2 and GOLD 3.01 were performed using the X-ray crystal structure of Mtb LprG protein to calculate the affinity and specificity of the analogs with the given LprG protein. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has a higher hypothetical affinity, also has greater negative value. Further, the non-specific ligands were screened out using the structural filter proposed by Baell and Holloway. Based on the USRCAT, Lipinski’s values, toxicity and BBB analysis, the drug-like analogs of fingolimod and BG-12 showed that RTL and CHEMBL1771640, respectively are non-toxic and permeable to BBB. The successful docking and DSX analysis showed that RTL and CHEMBL1771640 could bind to the binding pocket of S1PR1 receptor protein of human with greater affinity than as compared to their parent compound (Fingolimod). In this study, we also found that all the drug-like analogs of the standard MS drugs passed the Bell and Holloway filter.

Keywords: antagonist, binding affinity, chemotherapeutics, drug-like, multiple sclerosis, S1PR1 receptor protein

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Authors: D. Desai, J.Dixon, N. Jain, M. Datta

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Microbial infections of scalp consist of symptomatic appearances associated with seborrhoeic dermatitis, folliculitis, furuncles, carbuncles and ringworm. The main causative organisms in these scalp-based infections are bacteria like S. aureus, P. aeruginosa and a fungus M. Furfur. Allopathic treatment of these infections is available and efficient, but occasionally, topical applications have been found to cause side effects. India is known as the botanical garden of the world and considered as the epicentre for utilization of traditional drugs. Many treatments based on herb extracts are commonly used in India. It has been observed treatment with ethnomedicines requires a higher dosage and greater time period. Additionally, repeated applications are required to obtain the full efficacy of the treatment. An attempt has been made to imbibe the traditional knowledge with nanotechnology to generate a proficient therapeutic against scalp infections. We have imbibed metallic nanoparticles with extracts from traditional medicines and propose to formulate an antimicrobial hair massager. Four commonly used herbs for treatment against scalp disorders like Zingiber officinale (ginger), Allium sativum (garlic), Azadirachta indica (neem) leaves and Citrus limon (lemon) peel was taken. 30 gms of dried homogenized powder was obtained and processed for obtaining the aqueous and ethanolic extract by soxhlet apparatus. The extract was dried and reconstituted to obtain working solution of 1mg/ml. Phytochemical analysis for the obtained extract was done. Synthesis of nanoparticles was mediated by incubating 1mM silver nitrate with extracts of various herbs to obtain silver nanoparticles. The formation of the silver nanoparticles (AgNPs) was monitored using UV-Vis spectroscopy. The AgNPs thus obtained were centrifuged and dried. The AgNPs thus formed were characterized by X Ray Diffraction, scanning electron microscopy and transmission electron microscopy. The size of the AgNPs varied from 10-20 nm and was spherical in shape. P. aeruginosa was plated on nutrient agar and comparative antibacterial activity was tested. Comparative antimicrobial potential was calculated for the extracts and the corresponding nanoconstructs. It was found AgNPs were more efficient than their aqueous and ethanolic counterparts except in the ase of C. limon. Statistical analysis was performed to validate the results obtained.

Keywords: ethnomedicine, nanoconstructs, scalp infections, Zingiber officinale

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Authors: R. K. Purohit

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Ionizing radiation induces cellular damage through direct ionization of DNA and other cellular targets and indirectly via reactive oxygen species which may include effects from epigenetic changes. So there is a need of hour is to search for an ideal radioprotector which could minimize the deleterious and damaging effects caused by ionizing radiation. Radioprotectors are agents which reduce the radiation effects on cell when applied prior to exposure of radiation. The aim of this study was to access the efficacy of Emblica officinalis in reducing radiation and lead induced changes in mice liver. For the present experiment, healthy male Swiss albino mice (6-8 weeks) were selected and maintained under standard conditions of temperature and light. Fruit extract of Emblica was fed orally at the dose of 0.01 ml/animal/day. The animal were divided into seven groups according to the treatment i.e. lead acetate solution as drinking water (group-II) or exposed to 3.5 or 7.0 Gy gamma radiation (group-III) or combined treatment of radiation and lead acetate (group-IV). The animals of experimental groups were administered Emblica extract seven days prior to radiation or lead acetate treatment (group V, VI and VII) respectively. The animals from all the groups were sacrificed by cervical dislocation at each post-treatment intervals of 1, 2, 4, 7, 14 and 28 days. After sacrificing the animals pieces of liver were taken out and some of them were kept at -20°C for different biochemical parameters. The histopathological changes included cytoplasmic degranulation, vacuolation, hyperaemia, pycnotic and crenated nuclei. The changes observed in the control groups were compared with the respective experimental groups. An increase in the value of total proteins, glycogen, acid phosphtase, alkaline phosphatase activity and RNA was observed up to day-14 in the non drug treated group and day 7 in the Emblica treated groups, thereafter value declined up to day-28 without reaching to normal. The value of cholesterol and DNA showed a decreasing trend up to day -14 in non drug treated groups and day-7 in drug treated groups, thereafter value elevated up to day-28. The biochemical parameters were observed in the form of increase or decrease in the values. The changes were found dose dependent. After combined treatment of radiation and lead acetate synergistic effect were observed. The liver of Emblica treated animals exhibited less severe damage as compared to non-drug treated animals at all the corresponding intervals. An early and fast recovery was also noticed in Emblica pretreated animals. Thus, it appears that Emblica is potent enough to check lead and radiation induced heptic lesion in Swiss albino mice.

Keywords: radiation, lead , emblica, mice, liver

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

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

Keywords: bioengineering, cancer, nanomedicine, polymer chemistry

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Authors: Amy Stringer, Resa Chandler

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High Intensity Interval Training (HIIT) involves a 3-10-minute circuit of various exercises which is a viable alternative to a traditional cardiovascular and strength training regimen. Research suggests that measures of health-related fitness can either be maintained or actually improve with the use of this training method. After conducting a 6-week HIIT research study with 10-14 year old children, considerations for using a daily HIIT workout are presented. Is the use of HIIT with children a reasonable consideration for physical education programs? The benefits and challenges of this type of an intervention are identified. This study is significant in that achieving fitness gains in a small amount of daily class time is an attractive concept – especially for physical education teachers who often do not have the time necessary to accomplish all of their curricular goals in the amount of class time assigned. Basic methodologies include students participating in a circuit of exercises for 7-10 minutes at 80-95% of max heart rate as measured by heart rate monitors. Student pre and post fitness test data were collected for cardio-vascular endurance, muscular endurance, and body composition. Research notes as well as commentary by the teachers and researchers who participated in the HIIT study contributed to the understanding of the cost-benefit analysis. Major findings of the study are that HIIT has limited effectiveness but is a good choice for limited class times. Student efficacy of their ability to complete the exercises and visible heart rate data were considered to be significant factors in success of the HIIT study. The effective use of technology promoting positive audience effect during the display of heart rate data was more important at the beginning of the study than at the end. Student ‘buy-in’ and motivation, teacher motivation and ‘buy-in’, the variety of activities in the circuit and the fitness level of the student at the beginning of the study were also findings influencing the fitness outcomes of the study. Concluding Statement: High intensity interval training can be used effectively in a secondary physical education program. It is not a ‘magic bullet’ to produce health-related fitness outcomes in every student but it is an effective tool to enhance student fitness in a limited time and contribute to the goals of the program.

Keywords: cardio vascular fitness, children, high intensity interval training, physical education

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Authors: Lalita Subedi, Jae Kyoung Chae, Yong Un Park, Cho Kyo Hee, Lee Jae Hyuk, Kang Min Cheol, Sun Yeou Kim

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Neuroinflammation may mediate the relationship between low levels of estrogens and neurodegenerative disease. Estrogens are neuroprotective and anti-inflammatory in neurodegenerative disease models. Due to the long term side effects of estrogens, researches have been focused on finding an effective phytoestrogens for biological activities. Daidzein present in soybeans and its active metabolite equol (7-hydroxy-3-(4'-hydroxyphenyl)-chroman) bears strong antioxidant and anticancer showed more potent anti-inflammatory and neuroprotective role in neuroinflammatory model confirmed its in vitro activity with molecular mechanism through NF-κB pathway. Three major CNS cells Microglia (BV-2), Astrocyte (C6), Neuron (N2a) were used to find the effect of equol in inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), MAPKs signaling proteins, apoptosis related proteins by western blot analysis. Nitric oxide (NO) and prostaglandin E2 (PGE2) was measured by the Gries method and ELISA, respectively. Cytokines like tumor necrosis factor-α (TNF-α) and IL-6 were also measured in the conditioned medium of LPS activated cells with or without equol. Equol inhibited the NO production, PGE-2 production and expression of COX-2 and iNOS in LPS-stimulated microglial cells at a dose dependent without any cellular toxicity. At the same time Equol also showed promising effect in modulation of MAPK’s and nuclear factor kappa B (NF-κB) expression with significant inhibition of the production of proinflammatory cytokine like interleukin -6 (IL-6), and tumor necrosis factor -α (TNF-α). Additionally, it inhibited the LPS activated microglia-induced neuronal cell death by downregulating the apoptotic phenomenon in neuronal cells. Furthermore, equol increases the production of neurotrophins like NGF and increase the neurite outgrowth as well. In conclusion the natural daidzein metabolite equol are more active than daidzein, which showed a promising effectiveness as an anti-neuroinflammatory and neuroprotective agent via downregulating the LPS stimulated microglial activation and neuronal apoptosis. This work was supported by Brain Korea 21 Plus project and High Value-added Food Technology Development Program 114006-4, Ministry of Agriculture, Food and Rural Affairs.

Keywords: apoptosis, equol, neuroinflammation, phytoestrogen

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Authors: Mehrnaz Mostafavi

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Nanoliposomes, minute lipid-based vesicles at the nano-scale, show promise in the realm of photothermal therapy (PTT). This study presents an extensive overview of nanoliposomes in PTT, exploring their distinct attributes and the significant progress in this therapeutic methodology. The research delves into the fundamental traits of nanoliposomes, emphasizing their adaptability, compatibility with biological systems, and their capacity to encapsulate diverse therapeutic substances. Specifically, it examines the integration of light-absorbing materials, like gold nanoparticles or organic dyes, into nanoliposomal formulations, enabling their efficacy as proficient agents for photothermal treatment Additionally, this paper elucidates the mechanisms involved in nanoliposome-mediated PTT, highlighting their capability to convert light energy into localized heat, facilitating the precise targeting of diseased cells or tissues. This precise regulation of light absorption and heat generation by nanoliposomes presents a non-invasive and precisely focused therapeutic approach, particularly in conditions like cancer. The study explores advancements in nanoliposomal formulations aimed at optimizing PTT outcomes. These advancements include strategies for improved stability, enhanced drug loading, and the targeted delivery of therapeutic agents to specific cells or tissues. Furthermore, the paper discusses multifunctional nanoliposomal systems, integrating imaging components or targeting elements for real-time monitoring and improved accuracy in PTT. Moreover, the review highlights recent preclinical and clinical trials showcasing the effectiveness and safety of nanoliposome-based PTT across various disease models. It also addresses challenges in clinical implementation, such as scalability, regulatory considerations, and long-term safety assessments. In conclusion, this paper underscores the substantial potential of nanoliposomes in advancing PTT as a promising therapeutic approach. Their distinctive characteristics, combined with their precise ability to convert light into heat, offer a tailored and efficient method for treating targeted diseases. The encouraging outcomes from preclinical studies pave the way for further exploration and potential clinical applications of nanoliposome-based PTT.

Keywords: nanoliposomes, photothermal therapy, light absorption, heat conversion, therapeutic agents, targeted delivery, cancer therapy

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Authors: Birtukan Atinkut Asmare, Bernhard Freyer, Jim Bingen

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Though it is possible to transform the farming system towards a healthy, sustainable, and toxic-free food system by reducing pesticide use both in the field and postharvest, pesticides, including those that have been banned or severely restricted from use in developed countries, are indiscriminately used in African agriculture. Drawing on social practice theory, this study is about pesticide use practices in smallholder farms and its adverse impacts on women’s health and the environment, with reference to Africa, with an empirical focus on Ethiopia. Data have been collected via integrating diverse quantitative and qualitative approaches such as household surveys (n= 318), focus group discussions (n=6), field observations (n=30), and key informant interviews (n=18), with people along the pesticide value chain, including sellers and extension workers up to women farmers. A binary logistic regression model was used to investigate the factors that influence the adoption of personal protective equipment among female headed households. The findings show that Female-headed households carried out risky and unsafe practices from pesticide purchasing up to disposal, largely motivated by material elements (such as labor, income, time, and the provisioning system) but were notably shaped by competences (skills and knowledge), and meanings (norms, values, rules, and shared ideas). The main meaning or material aspect for pesticide purchasing were the perceptions of efficacy on pests, diseases, and weeds (65%), cost and availability in smaller quantities (60.7%), and a woman’s available time and mobility (58.9%). Pesticide hazards to human health or the environment seem not to be relevant for most female headed households. Unsafe practices of pesticide use among women led to the loss of biodiversity and ecosystem degradation, let alone their and family’s health. As the regression results show, the significant factors that influenced PPE adoption among female headed households were age and retailer information (p < 0.05). In line with the empirical finding, in addition to changing individual competences through advisory services and training, a foundational shift is needed in the sociocultural environment (e.g., policy, advisory), or a change in the meanings (social norms), where women are living and working.

Keywords: biodiversity, competences, ecosystems, ethiopia, female headed households, materials, meanings, pesticide purchasing, pesticide using, social practice theory

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Authors: Govinda Pathak

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In modern agriculture, the sustainable enhancement of crop productivity while minimizing environmental impacts remains a paramount challenge. Plant Growth Promoting Rhizobacteria (PGPR) have emerged as a promising solution to address this challenge. The rhizosphere, the dynamic interface between plant roots and soil, hosts intricate microbial interactions crucial for plant health and nutrient acquisition. PGPR, a subset of rhizospheric microorganisms, exhibit multifaceted beneficial effects on plants. Their abilities to stimulate growth, confer stress tolerance, enhance nutrient availability, and suppress pathogens make them invaluable contributors to sustainable agriculture. This work examines the pivotal role of free living nitrogen fixer in optimizing agricultural practices. We delve into the intricate mechanisms underlying PGPR-mediated plant-microbe interactions, encompassing quorum sensing, root exudate modulation, and signaling molecule exchange. Furthermore, we explore the diverse strategies employed by PGPR to enhance plant resilience against abiotic stresses such as drought, salinity, and metal toxicity. Additionally, we highlight the role of PGPR in augmenting nutrient acquisition and soil fertility through mechanisms such as nitrogen fixation, phosphorus solubilization, and mineral mobilization. Furthermore, we discuss the potential of PGPR in minimizing the reliance on chemical fertilizers and pesticides, thereby contributing to environmentally friendly agriculture. However, harnessing the full potential of PGPR requires a comprehensive understanding of their interactions with host plants and the surrounding microbial community. We also address challenges associated with PGPR application, including formulation, compatibility, and field efficacy. As the quest for sustainable agriculture intensifies, harnessing the remarkable attributes of PGPR offers a holistic approach to propel agricultural productivity while maintaining ecological balance. This work underscores the promising prospect of free living nitrogen fixer as a panacea for addressing critical agricultural challenges regarding chemical urea in an era of sustainable and resilient food production.

Keywords: PGPR, nitrogen fixer, quorum sensing, Rhizobacteria, pesticides

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Authors: Athena Daniilidou, Maria Platsidou

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Resilience is considered to greatly affect the personal and occupational wellbeing and efficacy of individuals; therefore, it has been widely studied in the social and behavioral sciences. Given its significance, several scales have been created to assess resilience of children and adults. However, most of these scales focus on examining only the internal protective or risk factors that affect the levels of resilience. The aim of the present study is to create a reliable scale that assesses both the internal and the external protective factors that affect Greek teachers’ levels of resilience. Participants were 136 secondary school teachers (89 females, 47 males) from urban areas of Greece. Connor-Davidson Resilience Scale (CD-Risc) and Resilience Scale for Adults (RSA) were used to collect the data. First, exploratory factor analysis was employed to investigate the inner structure of each scale. For both scales, the analyses revealed a differentiated factor solution compared to the ones proposed by the creators. That prompt us to create a scale that would combine the best fitting subscales of the CD-Risc and the RSA. To this end, the items of the four factors with the best fit and highest reliability were used to create the ‘Teachers' resilience scale’. Exploratory factor analysis revealed that the scale assesses the following protective/risk factors: Personal Competence and Strength (9 items, α=.83), Family Cohesion Spiritual Influences (7 items, α=.80), Social Competence and Peers Support (7 items, α=.78) and Spiritual Influence (3 items, α=.58). This four-factor model explained 49,50% of the total variance. In the next step, a confirmatory factor analysis was performed on the 26 items of the derived scale to test the above factor solution. The fit of the model to the data was good (χ2/292 = 1.245, CFI = .921, GFI = .829, SRMR = .074, CI90% = .026-,056, RMSEA = 0.43), indicating that the proposed scale can validly measure the aforementioned four aspects of teachers' resilience and thus confirmed its factorial validity. Finally, analyses of variance were performed to check for individual differences in the levels of teachers' resilience in relation to their gender, age, marital status, level of studies, and teaching specialty. Results were consistent to previous findings, thus providing an indication of discriminant validity for the instrument. This scale has the advantage of assessing both the internal and the external protective factors of resilience in a brief yet comprehensive way, since it consists 26 items instead of the total of 58 of the CD-Risc and RSA scales. Its factorial inner structure is supported by the relevant literature on resilience, as it captures the major protective factors of resilience identified in previous studies.

Keywords: protective factors, resilience, scale development, teachers

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Authors: Liudmila Garzanova, Lidia Ananyeva, Olga Koneva, Olga Ovsyannikova, Oxana Desinova, Mayya Starovoytova, Rushana Shayahmetova, Anna Khelkovskaya-Sergeeva

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Abstract Objectives. Rituximab (RTX) shown a positive effect in the treatment of systemic sclerosis (SSc). But there is still not enough data on comparing the effectiveness of RTX with immunosuppressants (IS). The aim of our study was to compare changes of lung function and skin score in SSc between two groups of patients (pts) - on RXT therapy (prescribed after ineffectiveness of previous therapy with IS) and on therapy with IS only. Methods. This study included 103 pts received RTX as an addition to previous therapy (group 1) and 65 pts received therapy with IS and prednisolone (group 2). The mean follow-up period was 12.6±10.7months. In group 1 the mean age was 47±12.9 years, female – 88 pts (84%), the diffuse cutaneous subset of the disease had 55 pts (53%). The mean disease duration was 6.2±5.5 years. 82% pts had interstitial lung disease (ILD) and 92% were positive for ANA, 67% of them were positive for antitopoisomerase-1. All pts received prednisolone at a dose of 11.3±4.5 mg/day, IS at inclusion received 47% of them. The cumulative mean dose of RTX was 1.7±0.6 g. In group 2 the mean age was 50.8±13.8 years, female-53 pts (82%), the diffuse cutaneous subset of the disease had 44 pts (68%). The mean disease duration was 8.8±7.7 years. 81% pts had ILD and 88% were positive for ANA, 58% of them were positive for antitopoisomerase-1. All pts received prednisolone at a dose of 8.69±4.28 mg/day, IS received 57% of them. Cyclophosphamide (CP) received 45% of pts. The cumulative mean dose of CP was 10.2±15.1g. D-penicillamine received 30% of pts. Other pts was on mycophenolate mofetil or methotrexate therapy in single cases. The pts of the compared groups did not differ in the main demographic and clinical parameters. The results are presented as delta (Δ) - difference between the baseline parameter and follow up point. Results. In group 1 there was an improvement of all outcome parameters: increased of forced vital capacity, % predicted - ΔFVC=4% (p=0.0004); Diffusing capacity for carbon monoxide, % predicted remained stable (ΔDLCO=0.1%); improvement of the Rodnan skin score-ΔmRss=3.4 (p=0.001); decrease of Activity index (EScSG-AI) - ΔActivity index=1.7 (p=0.001). In group 2 the changes was insignificant: ΔFVC=-2.3%, ΔmRss=0.87, ΔActivity index=0.3. But there was a significant decrease of DLCO: ΔDLCO=-5.1% (p=0.001). Conclusion. The results of our study confirm the data on the positive effect of RTX in complex therapy in pts with SSc (decrease of skin induration, increase of FVC, stabilization of DLCO). Meantime, pts on IS and prednisolone therapy shown the worsening of lung function and insignificant changes of other clinical parameters. RTX could be considered as a more effective option in complex treatment of SSc in comparison with IS therapy

Keywords: immunosuppressants, interstitial lung disease, systemic sclerosis, rituximab

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Authors: Lin Po-Hsi, Sheu Ming-Thau

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

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

Procedia PDF Downloads 116

Authors: Mehves Isiklar Ekici, Ceyda Tuna Kirsaclioglu, Zarife Kuloglu, Aydan Kansu

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Malnutrition is an important cause of morbidity and mortality as it accounts for 45% of child deaths under the age of 5 worldwide. Therefore, early recognition and effective treatment of failure to thrive and malnutrition are important. In this study, it was aimed to retrospectively evaluate the nutritional support treatment approaches (nutrition education and diet enrichment / use of enteral nutrition products) applied in children followed up with growth failure without underlying organic causes, and to compare the efficacy of nutritional support treatments. In this study, children aged 1 month to 18 years diagnosed with growth failure who were followed up for at least 12 months between January 2011 and February 2020, were included. Anthropometric measurements at baseline and during follow-up, type of nutritional support therapy and treatment compliance were evaluated based on the retrospective records. 119 children (median age:3.2, 69 girls) were included in the study. Nutrition education and dietary enrichment were provided to 28% of the patients (Group 1). In addition to dietary education and recommendations, enteral nutrition supplements was given in 78% of them (Group 2). Compliance to the treatment rates of the patients in Group 1 and Group 2 were not significantly different at both 6th and 12th month controls. At the end of the follow up children who comply with the treatment in Group 1 had significant increase in weight for age z scores (-1.74 vs 0.05, respectively, p=0.019) and body mass index z scores (-1.47 vs -0.53, respectively, p=0.034) compared with baseline measurements. Similar to Group 1, in Group 2 children with treatment compliance, had a significant increase in weight for age z scores (-2.24 vs. -0.54, respectively, p=0.00) and body mass index z scores (-2.27 vs. -1.06, respectively, p=0.00) compared with baseline measurements. The rate of patients with severe malnutrition decreased from 15% to 12%, for moderate malnutrition decreased from 54% to 33%. Moreover, it was observed that this decrease in the rate of patients with both severe and moderate malnutrition was more prominent in patients under 3 years of age. Although there was a significant increase in anthropometric measurements with treatment in both groups, there was no significant difference in between two groups terms of change in anthropometric measurements (p>0.05), therefore effectiveness. Failure to thrive and malnutrition in infancy and childhood cause health problems that can affect adult life. To conclude, nutritional education - dietary enrichment. recommendations and use of enteral nutrition supplements were both proven beneficial in this study. Researchers are willing to underline that the most important part of the treatment is to include the family to the process to ensure the treatment compliance.

Keywords: enteral nutrition supplements, failure to thrive, malnutrition, nutritional education

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Authors: Sharat Chandra, Zilong Wang, Ru-Rong Ji, Andrey Bortsov

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Chronic pain (CP) therapeutic approaches have limited efficacy. As a result, doctors are prescribing opioids for chronic pain, leading to opioid overuse, abuse, and addiction epidemic. Therefore, the development of effective and safe CP drugs remains an unmet medical need. Voltage-gated sodium (Nav) channels act as cardiovascular and neurological disorder’s molecular targets. Nav channels selective inhibitors are hard to design because there are nine closely-related isoforms (Nav1.1-1.9) that share the protein sequence segments. We are targeting the Nav1.7 found in the peripheral nervous system and engaged in the perception of pain. The objective of this project was to screen a 1.5 million compound library for identification of inhibitors for Nav1.7 with analgesic effect. In this study, we designed a protocol for identification of isoform-selective inhibitors of Nav1.7, by utilizing the prior information on isoform-selective antagonists. First, a similarity search was performed; then the identified hits were docked into a binding site on the fourth voltage-sensor domain (VSD4) of Nav1.7. We used the FTrees tool for similarity searching and library generation; the generated library was docked in the VSD4 domain binding site using FlexX and compounds were shortlisted using a FlexX score and SeeSAR hyde scoring. Finally, the top 25 compounds were tested with molecular dynamics simulation (MDS). We reduced our list to 9 compounds based on the MDS root mean square deviation plot and obtained them from a vendor for in vitro and in vivo validation. Whole-cell patch-clamp recordings in HEK-293 cells and dorsal root ganglion neurons were conducted. We used patch pipettes to record transient Na⁺ currents. One of the compounds reduced the peak sodium currents in Nav1.7-HEK-293 stable cell line in a dose-dependent manner, with IC50 values at 0.74 µM. In summary, our computer-aided analgesic discovery approach allowed us to develop pre-clinical analgesic candidate with significant reduction of time and cost.

Keywords: chronic pain, voltage-gated sodium channel, isoform-selective antagonist, similarity search, virtual screening, analgesics development

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Authors: Carolina Beltran, Carlos De Los Reyes

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Acquired brain injury (ABI) is any physical and functional injury secondary to events that affect the brain tissue. It is one of the biggest causes of disability in the world and it has a high annual incidence in the pediatric population. There are several causes of ABI such as traumatic brain injury, central nervous system infection, stroke, hypoxia, tumors and others. The consequences can be cognitive, behavioral, emotional and functional. The cognitive rehabilitation is necessary to achieve the best outcomes for pediatric people with ABI. Cognitive orientation to daily occupational performance (CO-OP) is an individualized client-centered, performance-based, problem-solving approach that focuses on the strategy used to support the acquisition of three client-chosen goals. It has demonstrated improvements in the pediatric population with other neurological disorder but not in Spanish speakers with ABI. Aim: The main objective of this study was to determine the efficacy of cognitive orientation to daily occupational performances (CO-OP) adapted to Spanish speakers, in the level of independence and behavior in a pediatric population with ABI. Methods: Case studies with measure pre/post-treatment were used in three children with ABI, sustained at least before 6 months assessment, in school, aged 8 to 16 years, age ABI after 6 years old and above average intellectual ability. Twelve sessions of CO-OP adapted to Spanish speakers were used and videotaped. The outcomes were based on cognitive, behavior and functional independence measurements such as Child Behavior Checklist (CBCL), Behavior Rating Inventory of Executive Function (BRIEF), The Vineland Adaptive Behavior Scales (VINELAND, Social Support Scale (MOS-SSS) and others neuropsychological measures. This study was approved by the ethics committee of Universidad del Norte in Colombia. Informed parental written consent was obtained for all participants. Results: children were able to identify three goals and use the global strategy ‘goal-plan-do-check’ during each session. Verbal self-instruction was used by all children. CO-OP showed a clinically significant improvement in goals regarding with independence level and behavior according to parents and teachers. Conclusion: The results indicated that CO-OP and the use of a global strategy such as ‘goal-plan-do-check’ can be used in children with ABI in order to improve their specific goals. This is a preliminary version of a big study carrying in Colombia as part of the experimental design.

Keywords: cognitive rehabilitation, acquired brain injury, pediatric population, cognitive orientation to daily occupational performance

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Authors: Yuanyuan Song

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Background: As we all know, culture plays a pivotal role in the realm of education, influencing study perceptions and outcomes. Nevertheless, there remains a need to delve into how culture specifically impacts the perception of courses. Therefore, the impact of culture on students' perceptions and academic performance is explored in this study. Drawing from cultural constructionism and conflict theories, it is posited that when students hailing from diverse cultures and backgrounds converge in the same classroom, their perceptions of course content may diverge significantly. This study seeks to unravel the tangible disparities and ascertain how cultural nuances shape students' perceptions of classroom content when encountering diverse cultural contexts within the same learning environment. Methodology: Given the diverse cultural backgrounds of students within the US, this study draws upon data collected from a course offered by a US college. In pursuit of answers to these inquiries, a qualitative approach was employed, involving semi-structured interviews conducted in a college-level science class in the US during 2023. The interviews encompassed approximately nine questions, spanning demographic particulars, cultural backgrounds, science learning experiences, academic outcomes, and more. Participants were exclusively drawn from science-related majors, with each student originating from a distinct cultural context. All participants were undergraduates, and most of them were from eighteen to twenty-five years old, totaling six students who attended the class and willingly participated in the interviews. The duration of each interview was approximately twenty minutes. Results: The findings gleaned from the interview data underscore the notable impact of varying cultural contexts on students' perceptions. This study argues that female science students, for instance, are influenced by gender dynamics due to the predominant male presence in science majors, creating an environment where female students feel reticent about expressing themselves in public. Students of East Asian origin exhibit a stronger belief in the efficacy of personal efforts when contrasted with their North American counterparts. Minority students indicated that they grapple with integration into the predominantly white mainstream society, influencing their eagerness to engage in classroom activities that are conducted by white professors. All of them emphasized the importance of learning science.

Keywords: multiculture education, educational sociology, educational equality, STEM education

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Authors: Josine Beek, S. Agten, R. Del Pozo, B. Balis

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The objective of the present study was to compare the safety of intramuscular administration of Zuprevo® (tildipirosin, 40 mg/mL) with Draxxin® (tulathromycin, 100 mg/mL) in the treatment of swine respiratory disease at weaning age. The trial was carried out in two farrow-to-finish farms with 300 sows (farm A) and 500 sows (farm B) in a batch-production system. Farm A had no history of respiratory problems, whereas farm B had a history of respiratory outbreaks with increased mortality ( > 2%) in the nursery. Both farms were positive to Pasteurella multocida, Bordetella bronchiseptica, Actinobacillus pleuropneumoniae and Haemophilus parasuis. From each farm, one batch of piglets was included (farm A: 644 piglets; farm B: 963 piglets). One day before weaning (day 0; 18-21 days of age), piglets were identified by an individual ear tag and randomly assigned to a treatment group. At day 0, Group 1 was treated with a single intramuscular injection with Zuprevo® (tildipirosin, 40 mg/mL; 1 mL/10 kg) and group 2 with Draxxin® (tulathromycin, 100 mg/mL; 1 mL/40 kg). For practical reasons, dosage of the product was adjusted according to three weight categories: < 4 kg, 4-6 kg and > 6 kg. Within each farm, piglets of both groups were comingled at weaning and subsequently managed and located in the same facilities and with identical environmental conditions. Our study involved the period from day 0 until 10 weeks of age. Safety of treatment was evaluated by 1) visual examination for signs of discomfort directly after treatment and after 15 min, 1 h and 24 h and 2) mortality rate within 24 h after treatment. Efficacy of treatment was evaluated based on mortality rate from day 0 until 10 weeks of age. Each piglet that died during the study period was necropsied by the herd veterinarian to determine the probable cause of death. Data were analyzed using binary logistic regression and differences were considered significant if p < 0.05. The pig was the experimental unit. In total, 848 piglets were treated with tildipirosin and 759 piglets with tulathromycin. In farm A, one piglet with retarded growth ( < 1 kg at 18 days of age) showed an adverse reaction after injection of tildipirosin: lateral recumbence and dullness for ± 30 sec. The piglet recovered after 1-2 min. This adverse reaction was probably due to overdosing (12 mg/kg). No adverse effect of treatment was observed in any other piglet. There was no mortality within 24 h after treatment. No significant difference was found in mortality rate between both groups from day 0 until 10 weeks of age. In farm A, overall mortality rate was 0.3% (2/644). In farm B, mortality rate was 0.2% (1/502) in group 1 (tildipirosin) and 0.9% (4/461) in group 2 (tulathromycin)(p=0.60). The necropsy of piglets that died during the study period revealed no macroscopic lesions of the respiratory tract. In conclusion, Zuprevo® (tildipirosin, 40 mg/mL) was shown to be a safe and efficacious alternative to Draxxin® (tulathromycin, 100 mg/mL) for the early treatment of swine respiratory disease at weaning age.

Keywords: antibiotic treatment, safety, swine respiratory disease, tildipirosin

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Authors: Mohammad Abu-Shaira, Weishi Shi

Abstract:

Adaptive learning, a commonly employed solution to drift, involves updating predictive models online during their operation to react to concept drifts, thereby serving as a critical component and natural extension for online learning systems that learn incrementally from each example. This paper introduces LSTM-SCCM “Long Short-Term Memory Stream Cruise Control Method”, a drift adaptation-as-a-service framework for online learning. LSTM-SCCM automates drift adaptation through prompt detection, drift magnitude quantification, dynamic hyperparameter tuning, performing shortterm optimization and model recalibration for immediate adjustments, and, when necessary, conducting long-term model recalibration to ensure deeper enhancements in model performance. LSTM-SCCM is incorporated into a suite of cutting-edge online regression models, assessing their performance across various types of concept drift using diverse datasets with varying characteristics. The findings demonstrate that LSTM-SCCM represents a notable advancement in both model performance and efficacy in handling concept drift occurrences. LSTM-SCCM stands out as the sole framework adept at effectively tackling concept drifts within regression scenarios. Its proactive approach to drift adaptation distinguishes it from conventional reactive methods, which typically rely on retraining after significant degradation to model performance caused by drifts. Additionally, LSTM-SCCM employs an in-memory approach combined with the Self-Adjusting Memory (SAM) architecture to enhance real-time processing and adaptability. The framework incorporates variable thresholding techniques and does not assume any particular data distribution, making it an ideal choice for managing high-dimensional datasets and efficiently handling large-scale data. Our experiments, which include abrupt, incremental, and gradual drifts across both low- and high-dimensional datasets with varying noise levels, and applied to four state-of-the-art online regression models, demonstrate that LSTM-SCCM is versatile and effective, rendering it a valuable solution for online regression models to address concept drift.

Keywords: automated drift detection and adaptation, concept drift, hyperparameters optimization, online and adaptive learning, regression

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