Search results for: therapeutic agents

Authors: Kyriaki Hatziagapiou, Eleni Kakouri, Konstantinos Bethanis, Alexandra Nikola, Eleni Koniari, Charalabos Kanakis, Elias Christoforides, George Lambrou, Petros Tarantilis

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Medulloblastoma is a highly invasive tumour, as it tends to disseminate throughout the central nervous system early in its course. Despite the high 5-year-survival rate, a significant number of patients demonstrate serious long- or short-term sequelae (e.g., myelosuppression, endocrine dysfunction, cardiotoxicity, neurological deficits and cognitive impairment) and higher mortality rates, unrelated to the initial malignancy itself but rather to the aggressive treatment. A strong rationale exists for the use of Crocus sativus L (saffron) and its bioactive constituents (crocin, crocetin, safranal) as pharmaceutical agents, as they exert significant health-promoting properties. Crocins are water soluble carotenoids. Unlike other carotenoids, crocins are highly water-soluble compounds, with relatively low toxicity as they are not stored in adipose and liver tissues. Crocins have attracted wide attention as promising anti-cancer agents, due to their antioxidant, anti-inflammatory, and immunomodulatory effects, interference with transduction pathways implicated in tumorigenesis, angiogenesis, and metastasis (disruption of mitotic spindle assembly, inhibition of DNA topoisomerases, cell-cycle arrest, apoptosis or cell differentiation) and sensitization of cancer cells to radiotherapy and chemotherapy. The current research aimed to study the potential cytotoxic effect of crocins on TE671 medulloblastoma cell line, which may be useful in the optimization of existing and development of new therapeutic strategies. Crocins were extracted from stigmas of saffron in ultrasonic bath, using petroleum-ether, diethylether and methanol 70%v/v as solvents and the final extract was lyophilized. Identification of crocins according to high-performance liquid chromatography (HPLC) analysis was determined comparing the UV-vis spectra and the retention time (tR) of the peaks with literature data. For the biological assays crocin was diluted to nuclease and protease free water. TE671 cells were incubated with a range of concentrations of crocins (16, 8, 4, 2, 1, 0.5 and 0.25 mg/ml) for 24, 48, 72 and 96 hours. Analysis of cell viability after incubation with crocins was performed with Alamar Blue viability assay. The active ingredient of Alamar Blue, resazurin, is a blue, nontoxic, cell permeable compound virtually nonfluorescent. Upon entering cells, resazurin is reduced to a pink and fluorescent molecule, resorufin. Viable cells continuously convert resazurin to resorufin, generating a quantitative measure of viability. The colour of resorufin was quantified by measuring the absorbance of the solution at 600 nm with a spectrophotometer. HPLC analysis indicated that the most abundant crocins in our extract were trans-crocin-4 and trans-crocin-3. Crocins exerted significant cytotoxicity in a dose and time-dependent manner (p < 0.005 for exposed cells to any concentration at 48, 72 and 96 hours versus cells not exposed); as their concentration and time of exposure increased, the reduction of resazurin to resofurin decreased, indicating reduction in cell viability. IC50 values for each time point were calculated ~3.738, 1.725, 0.878 and 0.7566 mg/ml at 24, 48, 72 and 96 hours, respectively. The results of our study could afford the basis of research regarding the use of natural carotenoids as anticancer agents and the shift to targeted therapy with higher efficacy and limited toxicity. Acknowledgements: The research was funded by Fellowships of Excellence for Postgraduate Studies IKY-Siemens Programme.

Keywords: crocetin, crocin, medulloblastoma, saffron

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Authors: Hyun Lim, Dong Sook Min, Han Eul Yun, Kil Tae Kim, Ya Nan Sun, Young Ho Kim, Hyun Pyo Kim

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Matrix metalloproteinase (MMP)-13 has an important role for degrading cartilage materials under inflammatory conditions such as arthritis. Since the 70% ethanol extract of Acanthopanax koreanum inhibited MMP-13 expression in IL-1β-treated human chondrocyte cell line, SW1353, two major constituents including acanthoic acid and impressic acid were initially isolated from the same plant materials and their MMP-13 down-regulating capacity was examined. In IL-1β-treated SW1353 cells, acanthoic acid and impressic acid significantly and concentration-dependently inhibited MMP-13 expression at 10 – 100 μM and 0.5 – 10 μM, respectively. The potent one, impressic acid, was found to inhibit MMP-13 expression by blocking the phosphorylation of signal transducer and activator of transcription-1/-2 (STAT-1/-2) and activation of c-Jun and c-Fos among cellular signaling pathway involved, but did not affect the activation of mitogen-activated protein kinases (MAPKs) and nuclear transcription factor-κB (NF-κB). Further, impressic acid was also found to inhibit the expression of MMP-13 mRNA (47.7% inhibition at 10 μM), the glycosaminoglycan release (42.2% reduction at 10 μM) and proteoglycan loss in IL-1-treated rabbit cartilage explants culture. For a further study, 21 impressic acid derivatives were isolated from the same plant materials and their suppressive activities against MMP-13 expression were examined. Among the derivatives, 3α-hydroxy-lup-20(29)-en-23-oxo,28-oic acid, (20R)-3α-hydroxy-29-dimethoxylupan-23,28-dioic acid, acankoreoside F and acantrifoside A clearly down-regulated MMP-13 expression, but impressic acid being most potent. All these results suggest that impressic acid, 3α-hydroxy-lup-20(29)-en-23-oxo,28-oic acid, (20R)-3α-hydroxy-29-dimethoxylupan-23,28-dioic acid, acankoreoside F, acantrifoside A and A. koreanum may have a potential for therapeutic agents to prevent cartilage degradation possibly by inhibiting matrix protein degradation.

Keywords: acanthoic acid, Acanthopanax koreanum, cartilage, impressic acid, matrix metalloproteinase

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Authors: Anton V. Dolzhenko, Tahir Mehmood Khan

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An ability to make an evidence-based decision is a critically important skill required for practicing pharmacists. The development of this skill is incorporated into the pharmacy curriculum. We aimed in our study to estimate perception of pharmacy students regarding herbal medicines and their ability to assess information on herbal medicines professionally. The current Monash University curriculum in Pharmacy does not provide comprehensive study material on herbal medicines and students should find their way to find information, assess its quality and make a professional decision. In the Pharmacy course, students are trained how to apply this process to conventional medicines. In our survey of 93 undergraduate students from year 1-4 of Pharmacy course at Monash University Malaysia, we found that students’ view on herbal medicines is sometimes associated with common beliefs, which affect students’ ability to make evidence-based conclusions regarding the therapeutic potential of herbal medicines. The use of herbal medicines is widespread and 95.7% of the participated students have prior experience of using them. In the scale 1 to 10, students rated the importance of acquiring herbal medicine knowledge for them as 8.1±1.6. More than half (54.9%) agreed that herbal medicines have the same clinical significance as conventional medicines in treating diseases. Even more, students agreed that healthcare settings should give equal importance to both conventional and herbal medicine use (80.6%) and that herbal medicines should comply with strict quality control procedures as conventional medicines (84.9%). The latter statement also indicates that students consider safety issues associated with the use of herbal medicines seriously. It was further confirmed by 94.6% of students saying that the safety and toxicity information on herbs and spices are important to pharmacists and 95.7% of students admitting that drug-herb interactions may affect therapeutic outcome. Only 36.5% of students consider herbal medicines as s safer alternative to conventional medicines. The students use information on herbal medicines from various sources and media. Most of the students (81.7%) obtain information on herbal medicines from the Internet and only 20.4% mentioned lectures/workshop/seminars as a source of such information. Therefore, we can conclude that students attained the skills on the critical assessment of therapeutic properties of conventional medicines have a potential to use their skills for evidence-based decisions regarding herbal medicines.

Keywords: evidence-based decision, pharmacy education, student perception, traditional medicines

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Authors: Chetna Tyagi. G. B. V. S. Lakshmi, Ambuj Tripathi, D. K. Avasthi

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Graphene oxide provides a good host matrix for preparing nanocomposites due to the different functional groups attached to its edges and planes. Being biocompatible, it is used in therapeutic applications. As enzyme-based biosensor requires complicated enzyme purification procedure, high fabrication cost and special storage conditions, we need enzyme-less biosensors for use even in a harsh environment like high temperature, varying pH, etc. In this work, we have prepared both enzyme-based and enzyme-less graphene oxide-based biosensors for glucose detection using glucose-oxidase as enzyme and gold nanoparticles, respectively. These samples were characterized using X-ray diffraction, UV-visible spectroscopy, scanning electron microscopy, and transmission electron microscopy to confirm the successful synthesis of the working electrodes. Electrochemical measurements were performed for both the working electrodes using a 3-electrode electrochemical cell. Cyclic voltammetry curves showed the homogeneous transfer of electron on the electrodes in the scan range between -0.2V to 0.6V. The sensing measurements were performed using differential pulse voltammetry for the glucose concentration varying from 0.01 mM to 20 mM, and sensing was improved towards glucose in the presence of gold nanoparticles. Gold nanoparticles in graphene oxide nanocomposite played an important role in sensing glucose in the absence of enzyme, glucose oxidase, as evident from these measurements. The selectivity was tested by measuring the current response of the working electrode towards glucose in the presence of the other common interfering agents like cholesterol, ascorbic acid, citric acid, and urea. The enzyme-less working electrode also showed storage stability for up to 15 weeks, making it a suitable glucose biosensor.

Keywords: electrochemical, enzyme-less, glucose, gold nanoparticles, graphene oxide, nanocomposite

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Authors: Brian Kristopher Cambra

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Millions of displaced families are seeking refuge in countries that are not their own due to war, violence, persecution, political unrest, and natural disasters. This global crisis is forcing researchers and practitioners to consider how refugees are coping with the trauma associated with their migration process. Effective therapeutic approaches are needed in a global effort to address the traumatic impact of forced migration. This meta-analytical study investigates the effectiveness of expressive therapeutic modalities, including play, art, music, sandplay, theatre, and writing therapies, in helping children and adolescents cope with refugee trauma. Seventeen pre-post and between-group comparison studies were analyzed using a random-effects model. The combined effect size for pre-post comparisons was medium (g = 0.58), whereas the combined effect size for between-group comparisons was small (g = 0.32). Overall, art therapy was found to be most effective in treating stress symptoms. Heterogeneity tests, however, suggest effect sizes cannot be interpreted as meaningful due to substantial variance. Nevertheless, findings of this meta-analysis indicate that expressive therapies may be among beneficial modalities to integrate with other trauma-informed approaches.

Keywords: expressive therapies, forced migration, meta-analysis, refugees, trauma

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Authors: Yaw Opoku-Damoah, Run Zhang, Hang Thu Ta, Zhi Ping Xu

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Gas therapy is still at an early stage of research and development. Even though most gasotransmitters have proven their therapeutic potential, their handling, delivery, and controlled release have been extremely challenging. This research work employs a versatile nanosystem that is capable of delivering a gasotransmitter in the form of a photo-responsive carbon monoxide-releasing molecule (CORM) for targeted cancer therapy. The therapeutic action was mediated by upconversion nanoparticles (UCNPs) designed to transfer bio-friendly low energy near-infrared (NIR) light to ultraviolet (UV) light capable of triggering carbon monoxide (CO) from a water-soluble amphiphilic manganese carbonyl complex CORM incorporated into a carefully designed lipid drug delivery system. Herein, gaseous CO that plays a role as a gasotransmitter with cytotoxic and homeostatic properties was investigated to instigate cellular apoptosis. After successfully synthesizing the drug delivery system, the ability of the system to encapsulate and mediate the sustained release of CO after light excitation was demonstrated. CO fluorescence probe (COFP) was successfully employed to determine the in vitro drug release profile upon NIR light irradiation. The uptake of nanoparticles enhanced by folates and its receptor interaction was also studied for cellular uptake purposes. The anticancer potential of the final lipid nanoparticle Lipid/UCNPs/CORM/FA (LUCF) was also determined by cell viability assay. Intracellular CO release and a subsequent therapeutic action involving ROS production, mitochondrial damage, and CO production was also evaluated. In all, this current project aims to use in vitro studies to determine the potency and efficiency of a NIR-mediated CORM prodrug delivery system.

Keywords: carbon monoxide-releasing molecule, upconversion nanoparticles, site-specific delivery, amphiphilic manganese carbonyl complex, prodrug delivery system.

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Authors: Ntokozo Dambuza, Maryna Van De Venter, Trevor Koekemoer

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Oxidative stress contributes to the pathogenesis of many diseases and consequently antioxidant therapy has attracted much attention as a potential therapeutic strategy. Regardless of the quantities ingested, antioxidants need to reach the diseased tissues at concentrations sufficient to combat oxidative stress. Bioavailability is thus a defining criterion for the therapeutic efficacy of antioxidants. In addition, therapeutic antioxidants must possess biologically relevant characteristics which can target the specific molecular mechanisms responsible for disease related oxidative stress. While many chemical antioxidant assays are available to quantify antioxidant capacity, they relate poorly to the biological environment and provide no information as to the bioavailability. The present comparative study thus aims to characterise green and fermented rooibos extracts, well recognized for their exceptional antioxidant capacity, in terms of antioxidant bioavailability and efficacy in a disease relevant cellular setting. Chinese green tea antioxidant activity was also evaluated. Chemical antioxidant assays (FRAP, DPPH and ORAC) confirmed the potent antioxidant capacity of both green and fermented rooibos, with green rooibos possessing antioxidant activity superior to that of fermented rooibos and Chinese green tea. Bioavailability was assessed using the PAMPA assay and the results indicate that green and fermented rooibos have a permeation coefficient of 5.7 x 10-6 and 6.9 x 10-6 cm/s, respectively. Chinese green tea permeability coefficient was 8.5 x 10-6 cm/s. These values were comparable to those of rifampicin, which is known to have a high permeability across intestinal epithelium with a permeability coefficient of 5 x 10 -6 cm/s. To assess the antioxidant efficacy in a cellular context, U937 and red blood cells were pre-treated with rooibos and Chinese green tea extracts in the presence of a dye DCFH-DA and then exposed to oxidative stress. Green rooibos exhibited highest activity with an IC50 value of 29 μg/ml and 70 μg/ml, when U937 and red blood cells were exposed oxidative stress, respectively. Fermented rooibos and Chinese green tea had IC50 values of 61 μg/ml and 57 μg/ml for U937, respectively, and 221 μg/ml and 405 μg/ml for red blood cells, respectively. These results indicate that fermented and green rooibos extracts were able to permeate the U937 cells and red blood cell membrane and inhibited oxidation of DCFH-DA to a fluorescent DCF within the cells.

Keywords: rooibos, antioxidants, permeability, bioavailability

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Authors: Kevser Cakmak, Adrián Montesano, Lourdes Artigas, Marta Salla, Clara Mateu

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The main objective of this research is to explore the relational letter writing technique as an intervention in couple therapy for reconnecting couples with their values and ethical preferences. This is a recently developed therapeutic tool within the framework of Narrative Therapy that consists of two interviews and a letter writing task, in which a meta-conversation between the relationship itself, the couple members, and the therapists is fostered. Although this specific therapeutic technique can be used within the therapy process, in this case study, it is used as a brief stand-alone narrative intervention for a middle age heterosexual couple breast cancer survivor. Couple’s relational and personal wellbeing was monitored before, during, and after the intervention by means of the dyadic adjustment and the clinical outcomes in routine evaluation-outcome measure, respectively. The couple showed a significant improvement after the intervention in both levels. The content of the letter writing exercises was qualitatively analysed to explore the reconstruction of their ethical values. Results from both methods are integrated in order to get an in-depth perspective of the newly developed tool. The potential of the letter writing technique as stand-alone and as adjunct brief intervention is discussed.

Keywords: couple therapy, narrative therapy, psychotherapy tool, relational letter writing

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Authors: Riham Barbar

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This paper studies the dynamic effects of charitable giving in a Ramsey model à la Becker and Foias (1994), such that heterogeneity is reduced to two types of agents: rich and poor. It is assumed that rich show a great concern for poor and enjoy giving. The introduction of charitable giving in this paper is inspired from the notion of Zakat (borrowed from the Islamic Economics) and is defined according to the warm-glow of Andreoni (1990). In this framework, we prove the existence of a steady state where only the patient agent holds capital. Furthermore, we show that local indetermincay appears. While moderate values of charitable-giving elasticity makes the appearance of endogenous fluctuations due to self-fulfilling expectations more likely, high values of this elasticity stabilizes endogenous fluctuations, by narrowing down the range of parameter values compatible with local indeterminacy and may rule out expectations-driven fluctuations if it exceeds certain threshold. Finally, cycles of period two emerge. However, charitable-giving makes it less likely for these cycles to emerge.

Keywords: charitable giving, warm-glow, bifurcations, heterogeneous agents, indeterminacy, self-fulfilling expectations, endogenous fluctuations

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Authors: Ashoke Priyadarshana Premananda

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As per the suggestions of previously conducted research in Counseling Psychology, the necessity of forming culture- friendly approaches has been strongly emphasized by a number of scholars in the field. In response to that, Multicultural-model of Buddhist Based Cognitive Behavioral Therapy (MMBCBT) has been formed as a culture-friendly therapeutic approach to address psychological disturbances (depression) in late adulthood. Elderly population in the world is on the rise by leaps and bounds, and forming a culture-based therapeutic model which is blended with Buddhist teachings has been the major objective of the study. Buddhist teachings and cultural applications, which were mapped onto Cognitive Behavioral Therapy (CBT) in the West, ultimately resulted in MMBCBT. Therefore, MMBCBT is a blend of cultural therapeutic techniques and the essence of certain Buddhist teachings extracted from five crucial suttas, which include CBT principles. In the process of mapping, MeghiyaSutta, GirimānandaSutta, SallekhaSutta, DvedhāvitakkaSutta, and Vitakka- SaṇṭhānaSutta have been taken into consideration mainly because of their cognitive behavioral content. The practical components of Vitakka- Saṇṭhānasutta (Aññanimittapabbaṃ) and Sallekhasutta (SallekhaPariyāya and CittuppādaPariyāya) have been used in the model while mindfulness of breathing was also carried out with the participants. Basically, multi-cultural therapeutic approaches of MMBCBT aim at modifying behavior (behavioral modification), whereas the rest is centered to the cognitive restructuring process. Therefore, MMBCBT is endowed with Behavioral Therapy (BT) and Cognitive Therapy(CT). In order to find out the validation of MMBCBT as a newly formed approach, it was then followed by mixed research (quantitative and qualitative research) with a sample selected from the elderly population following the purposive sampling technique. 40 individuals were selected from three elderly homes as per the purposive sampling technique. Elderly people identified to be depressed via Geriatric Depression Scale underwent MMBCBT for two weeks continuously while action research was being conducted simultaneously. Additionally, a Focus Group interview was carried out to support the action research. As per the research findings, people who identified depressed prior to the exposure to MMBCBT were found to be showing positive changes after they were exposed to the model. “Paired Sample t test” showed that the Multicultural Model of Buddhist based Cognitive Behavioral Therapy reduced depression of elderly people (The mean value (x̄) of the sample (level of depression) before the model was 10.7 whereas the mean value after the model was 7.5.). Most importantly, MMBCBT has been found to be effectively used with people from all walks of life despite religious diversities.

Keywords: buddhist psychotherapy, cognitive behavioral therapy in buddhism, counseling in cultural context, gerontology, and buddhism

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Authors: Giancarlo La Marca, Engy Shokry, Fabio Villanelli

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Epilepsy is one of the most common neurological disorders, with an estimated prevalence of 50 million people worldwide. Twenty five percent of the epilepsy population is represented in children under the age of 15 years. For antiepileptic drugs (AED), there is a poor correlation between plasma concentration and dose especially in children. This was attributed to greater pharmacokinetic variability than adults. Hence, therapeutic drug monitoring (TDM) is recommended in controlling toxicity while drug exposure is maintained. Carbamazepine (CBZ) is a first-line AED and the drug of first choice in trigeminal neuralgia. CBZ is metabolised in the liver into carbamazepine-10,11-epoxide (CBZE), its major metabolite which is equipotent. This develops the need for an assay able to monitor the levels of both CBZ and CBZE. The aim of the present study was to develop and validate a LC-MS/MS method for simultaneous quantification of CBZ and CBZE in dried blood spots (DBS). DBS technique overcomes many logistical problems, ethical issues and technical challenges faced by classical plasma sampling. LC-MS/MS has been regarded as superior technique over immunoassays and HPLC/UV methods owing to its better specificity and sensitivity, lack of interference or matrix effects. Our method combines advantages of DBS technique and LC-MS/MS in clinical practice. The extraction process was done using methanol-water-formic acid (80:20:0.1, v/v/v). The chromatographic elution was achieved by using a linear gradient with a mobile phase consisting of acetonitrile-water-0.1% formic acid at a flow rate of 0.50 mL/min. The method was linear over the range 1-40 mg/L and 0.25-20 mg/L for CBZ and CBZE respectively. The limit of quantification was 1.00 mg/L and 0.25 mg/L for CBZ and CBZE, respectively. Intra-day and inter-day assay precisions were found to be less than 6.5% and 11.8%. An evaluation of DBS technique was performed, including effect of extraction solvent, spot homogeneity and stability in DBS. Results from a comparison with the plasma assay are also presented. The novelty of the present work lies in being the first to quantify CBZ and its metabolite from only one 3.2 mm DBS disc finger-prick sample (3.3-3.4 µl blood) by LC-MS/MS in a 10 min. chromatographic run.

Keywords: carbamazepine, carbamazepine-10, 11-epoxide, dried blood spots, LC-MS/MS, therapeutic drug monitoring

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Authors: Srinivasarao Kondaparla, Utsab Debnath, Awakash Soni, Vasantha Rao Dola, Manish Sinha, Kumkum Kumkum Srivastava, Sunil K. Puri, Seturam B. Katti

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In a focused exploration, we have designed synthesized and biologically evaluated chiral conjugated new chloroquine (CQ) analogs with substituted piperazines as antimalarial agents. In vitro as well as in vivo studies revealed that compound 7c showed potent activity [for in vitro IC₅₀= 56.98nM (3D7), 97.76nM (K1); for in vivo (up to at the dose of 12.5 mg/kg); SI = 3510] as a new lead of antimalarial agent. Other compounds 6b, 6d, 7d, 7h, 8c, 8d, 9a, and 9c are also showing moderate activity against CQ-sensitive (3D7) strain and superior activity against resistant (K1) strain of P. falciparum. Furthermore, we have carried out docking and 3D-QSAR studies of all in-house data sets (168 molecules) of chiral CQ analogs to explain the structure activity relationships (SAR). Our new findings specified the significance of H-bond interaction with the side chain of heme for biological activity. In addition, the 3D-QSAR study against 3D7 strain indicated the favorable and unfavorable sites of CQ analogs for incorporating steric, hydrophobic and electropositive groups to improve the antimalarial activity.

Keywords: piperazines, CQ-sensitive strain-3D7, in-vitro and in-vivo assay, docking, 3D-QSAR

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Authors: Ananya Govindarajan

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Tetrahymena thermophila is a single-cell, eukaryotic organism that belongs to the Protozoa Kingdom. Tetrahymena thermophila is often used in signal transduction pathway studies because of its ability to model sensory input and the effects of environmental conditions such as chemicals and temperature. The recently discovered G37 chemorepellent receptor showed increased responsiveness to all chemorepellents. Investigating the mutant G37 Tetrahymena gene in various test solutions, including ferric chloride, ferrous sulfate, hydrogen peroxide, tetrazolium blue, potassium chloride, and dithiothreitol were performed to determine the role of oxidants and reducing agents with the mutant and wild-type cells (CU427) to assess the role of the receptor. Behavioral assays and recordings processed by ImageJ indicated that ferric chloride, hydrogen peroxide, and tetrazolium blue yielded little to no chemorepellent responses from G37 cells (<20% ARs). CU427 cells were over-responsive based on the mean percent of cells (>50% ARs). Reducing agents elicited chemorepellent responses from both G37 and CU427, in addition to potassium chloride. Cell responses were classified as over-responsive (>50% ARs). Dithiothreitol yielded unexpected results as G37 (37.0% ARs) and CU427 (38.1% ARs) had relatively similar responses and were only responsive and not over-responsive to the reducing agent test chemical solution. Ultimately, this indicates that the G37 receptor is more interactive with molecules that are reducing agents or non-oxidant compounds; G37 may be unable to sense and respond to oxidants effectively, further elucidating the pathways of the G37 strain and nature of this receptor. Results also indicate that the CSF most likely contained an oxidant, like ferric chloride. This research can be further applied to neuronal influences and how specific compounds may affect human neurons individually and their excitability as the responses model action potentials and membrane potential.

Keywords: tetrahymena thermophila, signal transduction, chemosensory, oxidant, reducing agent

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Authors: Youcef Serhane, Abdelkrim Bouzaza, Dominique Wolbert, Aymen Amin Assadi

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Throughout history, the use of chemical weapons is not exclusive to combats between army corps; some of these weapons are also found in very targeted intelligence operations (political assassinations), organized crime, and terrorist organizations. To improve the speed of action, important technological devices have been developed in recent years, in particular in the field of protection and decontamination techniques to better protect and neutralize a chemical threat. In order to assess certain protective, decontaminating technologies or to improve medical countermeasures, tests must be conducted. In view of the great toxicity of toxic chemical agents from (real) wars, simulants can be used, chosen according to the desired application. Here, we present an investigation about using a photocatalytic filtering reactor (PFR) for highly contaminated environments containing diethyl sulfide (DES). This target pollutant is used as a simulant of CWA, namely of Yperite (Mustard Gas). The influence of the inlet concentration (until high concentrations of DES (1200 ppmv, i.e., 5 g/m³ of air) has been studied. Also, the conversion rate was monitored under different relative humidity and different flow rates (respiratory flow - standards: ISO / DIS 8996 and NF EN 14387 + A1). In order to understand the efficacity of pollutant neutralization by PFR, a kinetic model based on the Langmuir–Hinshelwood (L–H) approach and taking into account the mass transfer step was developed. This allows us to determine the adsorption and kinetic degradation constants with no influence of mass transfer. The obtained results confirm that this small configuration of reactor presents an extremely promising way for the use of photocatalysis for treatment to deal with highly contaminated environments containing real chemical warfare agents. Also, they can give birth to an individual protection device (an autonomous cartridge for a gas mask).

Keywords: photocatalysis, photocatalytic filtering reactor, diethylsulfide, chemical warfare agents

Procedia PDF Downloads 104

Authors: Kabange Kasumbwe, Viresh Mohanlall, Bharti Odhav, Venu Narayanaswamy

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Coumarins are naturally occurring plant metabolites known for their pharmacological properties such as anticoagulant, antimicrobial, anticancer, antioxidant, anti-inflammatory and antiviral properties. The pharmacological and biochemical properties and curative applications of coumarins depend on the substitution around the coumarin core structure. In the present study, seven halogenated coumarins CMRN1-CMRN7 were synthesized and evaluated for their anticancer activity. The cytotoxicity potential of the test compounds was evaluated against UACC62 (Melanoma), MCF-7 (Breast cancer) and PBM (Peripheral Blood Mononuclear) cell lines using MTT assay keeping doxorubicin as standard drug. The apoptotic potential of the coumarin compounds was evaluated against UACC62 (Melanoma) cell by assessing their morphological changes, membrane change, mitochondria membrane potential; pro-apoptotic changes were investigated using the AnnexinV-PI staining, JC-1, caspase-3 enzyme kits respectively on flow cytometer. The synthetic coumarin has strongly suppressed the cell proliferation of UACC-62 (Melanoma) and MCF-7 (Breast) Cancer cells, the higher toxicity of these compounds against UACC-62 (Melanoma) and MCF-7 (Breast) were CMRN3, CMRN4, CMRN5, CMRN6. However, compounds CMRN1, CMRN2, and CMRN7 had no significant inhibitory effect. Furthermore the active compounds CMRN3, CMRN4, CMRN5, CMRN6 exerted antiproliferative effects through apoptosis induction against UACC-62 (Melanoma), suggesting their potential could be considered as attractive lead molecules in the future for the development of potential anticancer agents since one of the important criteria in the development of therapeutic drugs for cancer treatment is to have high selectivity and less or no side-effects on normal cells and these compounds had no inhibitory effect against the PBMC cells.

Keywords: coumarin, MTT, apoptosis, cytotoxicity

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Authors: Hak-Ryul Kim, Hyung-Geun Lee, Qi Long, Ching Hou

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Structural modification of natural lipids via chemical reaction or microbial bioconversion can change their properties or even create novel functionalities. Enzymatic oxidation of lipids leading to formation of oxylipin is one of those modifications. Hydroxy fatty acids, one of those oxylipins have gained important attentions because of their structural and functional properties compared with other non-hydroxy fatty acids. Recently 7,10-dihydroxy-8(E)-octadecenoic acid (DOD) was produced with high yield from lipid-containing oleic acid by microbial conversion, and the further study confirmed that DOD contained strong antimicrobial activities against a broad range of microorganisms. In this study, we tried to modify DOD molecules by the enzymatic or physical reaction to create new functionality or to enhance the antimicrobial activity of DOD. After modification of DOD molecules by different ways, we confirmed that the antimicrobial activity of DOD was highly enhanced and presented strong antimicrobial activities against multidrug-resistant Staphylococcus aureus, suggesting that DOD and its derivatives can be used as efficient antimicrobial agents for medical and industrial applications.

Keywords: biocatalysis, antimicrobial agent, multidrug-resistant bacteria, vegetable oil

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Authors: Yani Shi, Jiaqi Yan

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A new product is important for companies to extend consumers and manifest competitiveness. New product often involves new features that consumers might not be familiar with while it may also have a competitive advantage to attract consumers compared to established products. However, although most online retailers employ recommendation agents (RA) to influence consumers’ product choice decision, recommended new products are not accepted and chosen as expected. We argue that it might also be caused by providing a new product recommendation in the wrong way at the wrong time. This study seeks to discuss how new product evaluations sourced from third parties could be employed in RAs as evidence of the superiority for the new product and how the new product recommendation could be provided to a consumer at the right time so that it can be accepted and finally chosen during the consumer’s decision-making process. A 2*2 controlled laboratory experiment was conducted to understand the selection of new product recommendation sources and recommendation timing. Human subjects were randomly assigned to one of the four treatments to minimize the effects of individual differences on the results. Participants were told to make purchase choices from our product categories. We find that a new product recommended right after a similar existing product and with the source of the expert review will be more likely to be accepted. Based on this study, both theoretical and practical contributions are provided regarding new product recommendation.

Keywords: new product recommendation, recommendation timing, recommendation source, recommendation agents

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Authors: Habiba Rechek, Ammar Haouat, Ratiba Mekkiou, Diana C. G. A. Pinto, Artur M. S. Silva

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Satureja hispidula is an aromatic and medicinal plant belonging to the family of Lamiaceae native to Algeria, just like mint or thyme. Although she is less known to the general public than her more famous cousins, this species has many therapeutic properties that have been used for centuries in traditional medicine of some regions. For generations, Satureja hispidula has been used in traditional medicine to treat various ailments, including respiratory diseases and diabetes. Its aroma, often described as close to that of mint, gives it a special interest in aromatherapy. Due to the growing interest in the beneficial properties of plant-derived essential oils, the aim of this study is to analyze the chemical composition of S. hispidula essential oil by gas chromatography coupled with mass spectrometry (GC-MS). Identifying the main constituents of essential oil will allow better understanding its chemical nature and exploring its potential for culinary and therapeutic application. The study of the essential oil of S. hispidula reveals a composition rich in 83 compounds, including menthone, pulegone and piperitone as main constituents. This gas chromatography analysis coupled with mass spectrometry provides valuable information about the chemical nature of this oil. However, more in-depth studies are needed to explore the potentially health-enhancing properties of this essential oil.

Keywords: satureja hispidula, GC-MS, essential oil, menthone, pulegone

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Authors: Niharika Keot, Manabendra Sarma

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A thorough investigation of Ln3+ complexes with more than one inner-sphere water molecule is crucial for designing high relaxivity contrast agents (CAs) used in magnetic resonance imaging (MRI). This study accomplished a comparative stability analysis of two hexadentate (H3cbda and H3dpaa) and two heptadentate (H4peada and H3tpaa) ligands with Ln3+ ions. The higher stability of the hexadentate H3cbda and heptadentate H4peada ligands has been confirmed by the binding affinity and Gibbs free energy analysis in aqueous solution. In addition, energy decomposition analysis (EDA) reveals the higher binding affinity of the peada4− ligand than the cbda3− ligand towards Ln3+ ions due to the higher charge density of the peada4− ligand. Moreover, a mechanistic overview of water exchange kinetics has been carried out based on the strength of the metal–water bond. The strength of the metal–water bond follows the trend Gd–O47 (w) > Gd–O39 (w) > Gd–O36 (w) in the case of the tris-aquated [Gd(cbda)(H2O)3] and Gd–O43 (w) > Gd–O40 (w) for the bis-aquated [Gd(peada)(H2O)2]− complex, which was confirmed by bond length, electron density (ρ), and electron localization function (ELF) at the corresponding bond critical points. Our analysis also predicts that the activation energy barrier decreases with the decrease in bond strength; hence kex increases. The 17O and 1H hyperfine coupling constant values of all the coordinated water molecules were different, calculated by using the second-order Douglas–Kroll–Hess (DKH2) approach. Furthermore, the ionic nature of the bonding in the metal–ligand (M–L) bond was confirmed by the Quantum Theory of Atoms-In-Molecules (QTAIM) and ELF along with energy decomposition analysis (EDA). We hope that the results can be used as a basis for the design of highly efficient Gd(III)-based high relaxivity MRI contrast agents for medical applications.

Keywords: MRI contrast agents, lanthanide chemistry, thermodynamic stability, water exchange kinetics

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Authors: Di Luo, Maria Buchberger, Anja Pickhard

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Objectives: The purpose of this study was to assess and compare the diagnostic accuracy of four common morphological approaches, including sonography, computed tomography (CT), positron emission tomography/computed tomography (PET/CT), and magnetic resonance imaging (MRI) for the evaluation of cervical lymph node metastases in head and neck squamous cell carcinoma (HNSCC) patients. Material and Methods: Included in this retrospective study were 26 patients diagnosed with HNSCC between 2010 and 2011 who all underwent sonography, CT, PET/CT, and MRI imaging before neck dissection. Morphological data were compared to the corresponding histopathological results. Statistical analysis was performed with SPSS statistic software (version 26.0), calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for detection of cervical lymph node metastases. Results: The 5-year survival rate of the patient collective was 55.5%.Risk factors for survival included initial primary tumor stage, initial lymph node stage, initial metastasis status, and therapeutic approaches. Cox regression showed initial metastasis status(HR 8.671, 95%CI 1.316-57.123, p=0.025) and therapeutic approaches(HR 6.699, 95%CI 1.746-25.700, p=0.006)to be independent predictive risk factors for survival. Sensitivity was highest for MRI (96% compared to 85% for sonography and 89% for CT and PET/CT). Specificity was comparable with 95 % for CT and 98 % for sonography and PET/CT, but only 68% for MRI. While the MRI showed the least PPV (34%) compared to all other methods (85% for sonography,75% for CT, and 86% for PET/CT), the NPV was comparable in all methods(98-99%). The overall accuracy of cervical lymph node metastases detection was comparable for sonography, CT, and PET/CT with 96%,97%,94%, respectively, while MRI had only 72% accuracy. Conclusion: Since the initial status of metastasis is an independent predictive risk factor for patients’ survival, efficient detection is crucial to plan adequate therapeutic approaches. Sonography, CT, and PET/CT have better diagnostic accuracy than MRI for the evaluation of cervical lymph node metastases in HNSCC patients.

Keywords: cervical lymph node metastases, diagnostic accuracy, head and neck squamous carcinoma, risk factors, survival

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Authors: Ankit Nagar, Dinesh Kumar Nauriyal, S. P. Singh

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This paper examines farmers' perceptions of the efficacy of extension services in equipping them with the necessary information and skills required to maximise agricultural productivity. It is based on primary data collected through an interview schedule in India's Western Uttar Pradesh region. It uses descriptive statistics, factor analysis, and MANOVA to determine the typical farmer's view of an extension worker's technical prowess and behavioural traits, as well as the key factors associated with farmers' perception and the demographic characteristics that affect farmer's perception variations. The vast majority of farmers appear to consider extension personnel's efficiency and accessibility unfavourably. Farmers feel that extension personnel are well-trained notwithstanding their disagreements on the viability of their technical advice. Small and marginal farmers view the effectiveness, objectivity, and cooperativeness of extension agents less favourably than large farmers. This study proposes strategies such as routine follow-ups, practical demonstrations, and regular extension professional training camps as part of a holistic plan to increase farmer trust in the agricultural extension system. In addition, it proposes ensuring their accountability.

Keywords: agriculture extension, farmers’ perception, extension agents, factor analysis

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Authors: Atitallah Sofien, Missaoui Nada, Ben Rabeh Rania, Yahyaoui Salem, Mazigh Sonia, Bouyahia Olfa, Boukthir Samir

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Introduction: Acute bronchiolitis (AB) is a real public health problem on a global and national scale. Its treatment is most often outpatient. The use of audio-visual supports, such as educational videos, is an innovation in therapeutic education in outpatient treatment. The aim of our study was to evaluate the impact of an educational video on the knowledge, attitudes, and practices of mothers of infants with AB. Methodology: This was a descriptive, analytical, and cross-sectional study with prospective data collection, including mothers of infants with AB. We assessed mothers' knowledge, attitudes, and practices regarding AB, and we created an educational video. We used a questionnaire written in Tunisian Arabic concerning sociodemographic data, mothers' knowledge and attitudes regarding AB, and their opinions on the video, as well as an observation grid to evaluate their practices on the nasopharyngeal unblocking technique. We compared the different parameters before and after watching the video. Results: We noted a statistically significant improvement in mothers' knowledge scores on AB (7.46 in the pre-test versus 14.08 in the post-test; p≤0.05), practices (12.42 in the pre-test versus 18 in the post-test; p≤0.05) and attitudes (5.86 in pre-test versus 9.02 in post-test; p≤0.05). Conclusion: The use of an educational video has a positive impact on the knowledge, practices, and attitudes of mothers towards AB.

Keywords: acute bronchiolitis, therapeutic education, mothers, educational video

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Authors: Charlotte Zamani

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Children's and young people’s (CYP’s) perspectives on using client preference tools are central to understanding youth mental health therapy engagement. This systematic literature review attempts to understand the meanings of CYP using preference tools that may allow greater connection with the therapeutic process. Following a systematic search using PRISMA guidelines, seven studies were identified that reported qualitative feedback on preferred treatment options or activities within therapy. The data were analysed using interpretative phenomenological analysis (IPA). Three group experiential themes were found: ‘Tailor my support’, ‘My autonomy leads to greater engagement’ and ‘Preferences facilitate my authentic self’. CYP is broadly divided into those who thrive in decision-making and those who require more support. Being offered a choice in therapy delivery provides easier access and means more freedom for CYP. Preferences in therapy appeared to enable greater self-knowledge and a deeper connection to the therapeutic process. The therapist is integral in using preference tools in therapy. Youth feedback is currently limited, yet essential and ethical in order to understand critical factors of CYP engagement and for future research.

Keywords: child and adolescent, client preferences, mental health therapy, qualitative

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Authors: Mehani Mouna, Ladjel segni

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Humans use plants for thousands of years to treat various ailments, In many developing countries, Much of the population relies on traditional doctors and their collections of medicinal plants to cure them. Essential oils have many therapeutic properties. In herbal medicine, They are used for their antiseptic properties against infectious diseases of fungal origin, Against dermatophytes, Those of bacterial origin. The aim of our study is to determine the antimicrobial effect of essential oils of the plant Schinus molle on some pathogenic bacteria. It is a medicinal plant used in traditional therapy. Essential oils have many therapeutic properties. In herbal medicine, They are used for their antiseptic properties against infectious diseases of fungal origin, Against dermatophytes, Those of bacterial origin. The test adopted is based on the diffusion method on solid medium (Antibiogram), This method allows to determine the susceptibility or resistance of an organism according to the sample studied. Our study reveals that the essential oil of the plant Schinus molle has a different effect on the resistance of germs: For Pseudomonas aeruginosa strain is a moderately sensitive with an inhibition zone of 10 mm, Further Antirobactere, Escherichia coli and Proteus are strains that represent a high sensitivity, A zone of inhibition equal to 14.66 mm.

Keywords: Essential oil, microorganism, antibiogram, shinus molle

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Authors: Jiwan P. Lavande, A. V. Chandewar

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In the present study, orodispersible tablets of diphenhydramine hydrochloride were prepared using croscarmellose sodium, crospovidone and camphor, menthol (as subliming agents) in different ratios and ODTs prepared with superdisintegrants were compared with ODTs prepared with camphor and menthol (subliming agents) for the following evaluation of in vitro disintegration time, dispersion time, wetting time, hardness and water absorption ratio. Results revealed that the tablets of all formulations have acceptable physical parameters. The drug and excipients compatibility study was evaluated using FTIR technique and has not detected any incompatibility. The in vitro release of drug from DC6 formulation was quick when compared to other formulations. Stability study was carried out as per ICH guidelines for three months and results revealed that upon storage disintegration time of tablets had not shown any significant difference. Microscopic study of different formulations of sublimed tablets showed formation of pores for the tablets prepared by sublimation method. Thus, conclusion can be made that the stable orodispersible tablets of diphenhydramine hydrochloride can be developed for the rapid release of diphenhydramine hydrochloride.

Keywords: orodispersible tablet, subliming agent, super disintegrants, diphenhydramine hydrochloride

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Authors: Rafia S. Al-lamki, Jun Wang, Simon Pacey, Jordan Pober, John R. Bradley

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Tumor necrosis factor alpha (TNF), signaling through TNFR2, may act an autocrine growth factor for renal tubular epithelial cells. Clear cell renal carcinomas (ccRCC) contain cancer stem cells (CSCs) that give rise to progeny which form the bulk of the tumor. CSCs are rarely in cell cycle and, as non-proliferating cells, resist most chemotherapeutic agents. Thus, recurrence after chemotherapy may result from the survival of CSCs. Therapeutic targeting of both CSCs and the more differentiated bulk tumor populations may provide a more effective strategy for treatment of RCC. In this study, we hypothesized that TNFR2 signaling will induce CSCs in ccRCC to enter cell cycle so that treatment with ligands that engage TNFR2 will render CSCs susceptible to chemotherapy. To test this hypothesis, we have utilized wild-type TNF (wtTNF) or specific muteins selective for TNFR1 (R1TNF) or TNFR2 (R2TNF) to treat either short-term organ cultures of ccRCC and adjacent normal kidney (NK) tissue or cultures of CD133+ cells isolated from ccRCC and adjacent NK, hereafter referred to as stem cell-like cells (SCLCs). The effect of cyclophosphamide (CP), currently an effective anticancer agent, was tested on CD133+SCLCs from ccRCC and NK before and after R2TNF treatment. Responses to TNF were assessed by flow cytometry (FACS), immunofluorescence, and quantitative real-time PCR, TUNEL, and cell viability assays. Cytotoxic effect of CP was analyzed by Annexin V and propidium iodide staining with FACS. In addition, we assessed the effect of TNF on isolated SCLCs differentiation using a three-dimensional (3D) culture system. Clinical samples of ccRCC contain a greater number SCLCs compared to NK and the number of SCSC increases with higher tumor grade. Isolated SCLCs show expression of stemness markers (oct4, Nanog, Sox2, Lin28) but not differentiation markers (cytokeratin, CD31, CD45, and EpCAM). In ccRCC organ cultures, wtTNF and R2TNF increase CD133 and TNFR2 expression and promote cell cycle entry whereas wtTNF and R1TNF increase TNFR1 expression and promote cell death of SCLCs. Similar findings are observed in SCLCs isolated from NK but the effect was greater in SCLCs isolated from ccRCC. Application of CP distinctly triggered apoptotic and necrotic cell death in SLCSs pre-treatment with R2TNF as compared to CP treatment alone, with SCLCs from ccRCC more sensitive to CP compared to SLCS from NK. Furthermore, TNF promotes differentiation of SCLCs to an epithelial phenotype in 3D cultures, confirmed by cytokeratin expression and loss of stemness markers Nanog and Sox2. The differentiated cells show positive expression of TNF and TNFR2. These findings provide evidence that selective engagement of TNFR2 drive CSCs to cell proliferation/differentiation, and targeting of cycling cells with TNFR2 agonist in combination with anti-cancer agents may be a potential therapy for RCC.

Keywords: cancer stem cells, ccRCC, cell cycle, cell death, TNF, TNFR1, TNFR2, CD133

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Authors: Nahwera L., Constance A. N. Nsibamb, Mukana R., Daniel T. Goon

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Regular physical activity is a cornerstone of maintaining good health. Studies have shown that physical inactivity leads to overweight and obesity, a risk factor for non-communicable diseases and a public health challenge. Health clubs provide therapeutic exercises to clients desiring to reduce their weight; however, the exercise routines offered in these health clubs are insufficient to reduce their body weight. A convenient sample of 100 clients. Exercise routines were determined using a questionnaire. Height, weight, waist, and hip circumferences were measured. Body mass index (BMI), waist circumference, and waist-to-hip ratio (WHR) assessed body weight status. About 75% of clients exercised three or more times per week; 96% participated in modern intensity exercises for 30 minutes, aerobic dance (88%), treadmill (56%), cycling (51%), rope skipping (45%), and 14% in strengthening activities. The BMI of male and female clients was 64.2% and 83.0%, respectively. There was no significant correlation (p≤0.05) between BMI and WHR (p=0.336), although there was a significant correlation between BMI and waist circumference (p=0.000). There was no significant relationship between BMI and WHR for males (p= .336) and between BMI and WHR for females (p=.806). Although most clients visiting health clubs meet the recommended frequency, intensity, and duration of exercise, they are overweight and obese. Appropriate exercise and nutritional programs should be incorporated into health clubs offering therapeutic and rehabilitative exercises to clients.

Keywords: Body weight status, exercise routines, health clubs, exercises

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Authors: Ilona Bontenbal

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In this research, the potential for societal change is researched through the idea of migrants as change agents. The viewpoint is on the potential that migrants have for affecting societal change in their country of origin through transmitting transnational peer-to-peer information. The focus is on the information that Russian migrants living in Finland transmit about their experiences and attitudes regarding the Nordic welfare state, its democratic foundation and the social rights embedded in it, to their family and friends in their country of origin. The welfare provision and level of democracy are very different in the two neighbouring countries of Finland and Russia. Finland is a Nordic welfare state with strong democratic institutions and a comprehensive actualizing of civil and social rights. In Russia, the state of democracy has on the other hand been declining, and the social and civil rights of its citizens are constantly undermined. Due to improvements in communications and travel technology, migrants can easily and relatively cheaply stay in contact with their family and friends in their country of origin. This is why it is possible for migrants to act as change agents. By telling about their experiences and attitudes about living in a democratic welfare state, migrants can affect what people in the country or origin know and think about welfare, democracy, and social rights. This phenomenon is approached through the concept of social remittances. Social remittances broadly stand for the ideas, know-how, world views, attitudes, norms of behavior, and social capital that flows through transnational networks from receiving- to sending- country communities and the other way around. The viewpoint is that historically and culturally formed democratic welfare models cannot be copied entirely nor that each country should achieve identical development paths, but rather that migrants themselves choose which aspects they see as important to remit to their acquaintances in their country of origin. This way the potential for social change and the agency of the migrants is accentuated. The empirical research material of this study is based on 30 qualitative interviews with Russian migrants living in Finland. Russians are the largest migrant group in Finland and Finland is a popular migration destination especially for individuals living in North-West Russia including the St. Petersburg region. The interviews are carried out in 2018-2019. The preliminary results indicate that Russian migrants discuss social rights and welfare a lot with their family members and acquaintances living in Russia. In general, the migrants feel that they have had an effect on the way that their friends and family think about Finland, the West, social rights and welfare provision. Democracy, on the other hand, is seen as a more difficult and less discussed topic. The transformative potential that the transmitted information and attitudes could have outside of the immediate circle of acquaintances on larger societal change is seen as ambiguous although not negligible.

Keywords: migrants as change agents, Russian migrants, social remittances, welfare and democracy

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Authors: Lubisi L. V., Madumo M. B., Mudau N. P., Makhuvele L., Sibuyi M. M.

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Background and Aims: Learners with disabilities can be integrated into mainstream schools, whereas there are those learners that are accommodated in special schools based on the support needs they require. These needs, among others, pertain to access to high-intensity therapeutic support by physiotherapists, occupational therapists, and speech therapists. However, access to physiotherapists in low- and middle-income countries is limited, and this creates a knowledge gap in identifying, to the best of our knowledge, best practice patterns aligned with physiotherapy at special schools. This gap compromises the quality of support to be rendered towards strengthening rehabilitation and optimising the participation of learners with disabilities in special schools. The aim of the scoping review was to map the evidence on practice patterns employed by physiotherapists at special schools for learners with disabilities. Methods: The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were followed. Key terms regarding physiotherapy practice patterns for learners with disabilities at special schools were used to search the literature on the databases. Literature was sourced from Google Scholar, EBSCO, PEDro, PubMed, and Research Gate from 2013 to 2023. A total of 28 articles were initially retrieved and after a process of screening and exclusion, nine articles were included. All the researchers reviewed the articles for eligibility. Articles were initially screened based on the titles, followed by full text. Articles written in English or translated into English mentioned physical / physiotherapy interventions in special schools, both published and unpublished, were included. A qualitative data extraction template was developed and an inductive approach to thematic data analysis was used for included articles to see which themes emerged. Results: Three themes emerged after inductive thematic data analysis. 1. Collaboration with educators, parents, and therapists 2. Family Centred Approach 3. Telehealth. Conclusion: Collaboration is key in delivering therapeutic support to learners with disabilities at special schools. Physiotherapists need to be collaborators at the level of interprofessional and transprofessional. In addition, they need to explore technology to work remotely, especially when learners become absent physically from school.

Keywords: learners with disabilities, special school, physiotherapists, therapeutic support

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Authors: Shirui Huang, Wei Chen, Chuanshu Huang

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Basal muscle-invasive bladder cancer (BMIBC) is considered one of the subtypes of BC with the highest metastatic rate and the poorest prognosis. Therefore, elucidating the mechanisms underlying BMIBC metastasis and identifying novel precision therapeutic targets are current research hotspots and challenges to cancer researchers. Through a series of in vitro and in vivo functional experiments, we have identified the crucial role of KRT14 in the high invasiveness and adverse prognosis of BMIBC. We found that the K294 site within the IGF2BP1-KH2 domain is responsible for reading the conserved genetic information carried by D226/E227 in the KRT14 nuclear export signal (NES). Activation of the KRT14-IGF2BP1 signaling axis is essential for IGF2BP1-mediated stabilization of SNAI1 mRNA through FTO modification. Additionally, IGF2BP1 forms a positive feedback loop by stabilizing its own mRNA, thereby accelerating the invasion and metastasis of BMIBC. Collectively, our study identifies the KRT14/IGF2BP1/FTO/Snail signaling axis as an essential regulatory mechanism associated with poor prognosis in BMIBC, providing a theoretical basis for KRT14 and its downstream regulated molecules as therapeutic targets for BMIBC and the development of corresponding targeted therapies.

Keywords: BMIBC, KRT4, IFGF2BP1, DNA methylation

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