Search results for: in silico screening

Authors: Shaik Asha Begum, S. Joshna Rani, Shaik Abdul Rahaman

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INTRODUCTION: Breast cancer is a disease that creates in breast cells. "KAP" study estimates the Knowledge, Attitude, and Practices of a local area. More than 1.5 million ladies (25% of all ladies with malignancy) are determined to have bosom disease consistently all through the world. Understanding the degrees of Knowledge, Attitude and Practice will empower a more effective cycle of mindfulness creation as it will permit the program to be custom-made all the more properly to the necessities of the local area. OBJECTIVES: The objective of this study is to assess the knowledge on signs and symptoms, risk factors, provide awareness on the practicing of the early detection techniques of breast cancer and provide knowledge on the overall breast cancer including preventive techniques. METHODOLOGY: This is an expressive cross-sectional investigation. This investigation of KAP was done in the Nirmala Educational Institutions from January to April 2021. A total of 300 participants are included from women students in pharmacy graduates & lecturers, and also from graduates other than the pharmacy. The examiners are taken from the BCAM (Breast Cancer Awareness Measure), tool compartment (Version 2). RESULT: According to the findings of the study, the majority of the participants were not well informed about breast cancer. A lump in the breast was the most commonly mentioned sign of breast cancer, followed by pain in the breast or nipple. The percentage of knowledge related to the breast cancer risk factors was also very less. The correct answers for breast cancer risk factors were radiation exposure (58.20 percent), a positive family history (47.6 percent), obesity (46.9 percent), a lack of physical activity (43.6 percent), and smoking (43.2 percent). Breast cancer screening, on the other hand, was uncommon (only 30 and 11.3 percent practiced clinical breast examination and mammography respectively). CONCLUSION: In this study, the knowledge on the signs and symptoms, risk factors of breast cancer - pharmacy graduates have more knowledge than the non-pharmacy graduates but in the preventive techniques and early detective tools of breast cancer -had poor knowledge in the pharmacy and non-pharmacy graduate. After the awareness program, pharmacy and non-pharmacy graduates got supportive knowledge on the preventive techniques and also practiced the early detective techniques of breast cancer.

Keywords: breast cancer, mammography, KAP study, early detection

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Authors: Laura Amato, Paolo Mulatti, Fabrizio Montarsi, Matteo Mazzucato, Laura Gagliazzo, Michele Brichese, Manlio Palei, Gioia Capelli, Lebana Bonfanti

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West Nile virus (WNV) re-emerged in north-eastern Italy in 2008, after ten years from its first appearance in Tuscany. In 2009, a national surveillance programme was implemented, and re-modulated in north-eastern Italy in 2011. Hereby, we present the results of surveillance activities in 2008-2016 in the north-eastern Italian regions, with inferences on WNV epidemiological trend in the area. The re-modulated surveillance programmes aimed at early detecting WNV seasonal reactivation by searching IgM antibodies in horses. In 2013, the surveillance plans were further modified including a risk-based approach. Spatial analysis techniques, including Bernoulli space-time scan-statistics, were applied to the results of 2010–2012 surveillance on mosquitoes, equines, and humans to identify areas where WNV reactivation was more likely to occur. From 2008 to 2016, residential horses tested positive for anti-WNV antibodies on a yearly basis (503 cases), also in areas where WNV circulation was not detected in mosquito populations. Surveillance activities detected 26 syndromic cases in horses, 102 infected mosquito pools and WNV in 18 dead wild birds. Human cases were also recurrently detected in the study area during the surveillance period (68 cases of West Nile neuroinvasive disease). The recurrent identification of WNV in animals, mosquitoes, and humans indicates the virus has likely become endemic in the area. In 2016, findings of WNV positives in horses or mosquitoes were included as triggers for enhancing screening activities in humans. The evolution of the epidemiological situation prompts for continuous and accurate surveillance measures. The results of the 2013-2016 surveillance indicate that the risk-based approach was effective in early detecting seasonal reactivation of WNV, key factor of the integrated surveillance strategy in endemic areas.

Keywords: arboviruses, horses, Italy, surveillance, west nile virus, zoonoses

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Authors: Nitin Rajan, Kashif Shakeel, Shashank Tiwari, Shachan Sagar

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Background: - Aegle Marmelos (Bael) leaf extract is taken twice daily to treat ophthalmia, ulcers, and intestinal worms, among other ailments. Poultice made from bael leaf is used in the treatment of eye conditions. The leaf juice has a variety of therapeutic applications, with the most notable being the treatment of diabetes. Fenugreek is used to cure red spots around the eyes, as well as to soften the throat and chest and to give relief from coughing. The use of this plant in the form of infusion, powder, pomade, and decoction has been extremely popular in Iranian traditional medicine. The plant may be used to wash one's vaginal linings. This plant is used as an emollient in the lack of appetite, treatment of pellagra, and gastrointestinal problems, as well as a general tonic. Calendula officinalis leaves are used to treat varicose veins on the outside of the body by infusing them. In Europe, the leaves are diaphoretic and resolvent in nature, while the blooms are employed as an emmenagogue and antispasmodic stimulant in Canada and the United States. The flowers were decocted and served as a posset drink when smallpox and measles were common in England, and the fresh juice was used to treat jaundice. Objective: - This study is done to compare the physicochemical parameter of the alcoholic extract of the leaves of Aegle Marmelos, Calendula Officinalis, and Fenugreek. Materials and Methods: Extraction and Isolation of Aegle Marmelos, Calendula Officinalis, Fenugreek, were done. Preliminary phytochemical study for alkaloids, cardiac glycosides, flavonoids, glycosides, phenols, resins, saponins, steroids, tannins, terpenoids of the extract was done individual by using the standard procedure. Result: - The phytochemical screening of Aegle Marmelos, Calendula Officinalis, and Fenugreek shows the presence of alkaloids, carbohydrates, total phenolics, total flavonoids, tannins, saponins gum. Conclusion: - In this study, we have found that crude aqueous and organic solvent extracts of Aegle Marmelos, Calendula Officinalis, and Fenugreek leaves contain some important bioactive compounds and it justifies their use in the traditional medicines for the treatment of different diseases.

Keywords: Aegle Marmelos, Calendula Officinalis, Fenugreek, physiochemical parameter

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Authors: Pakinee Pooprasert, Wanxin Wang, Tina Parmar, Dana Ahnood, Tafadzwa Young-Zvandasara, James Morgan

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Homelessness has been shown to be correlated to poor health outcomes, including increased visual health morbidity. Despite this, there are relatively few studies regarding visual health in the homeless population, especially in the UK. This research aims to investigate visual disability and access barriers prevalent in the homeless population in Cardiff, South Wales. Data was collected from 100 homeless participants in three different shelters. Visual outcomes included near and distance visual acuity as well as non-cycloplegic refraction. Qualitative data was collected via a questionnaire and included socio-demographic profile, ocular history, subjective visual acuity and level of access to healthcare facilities. Based on the participants’ presenting visual acuity, the total prevalence of myopia and hyperopia was 17.0% and 19.0% respectively based on spherical equivalent from the eye with the greatest absolute value. The prevalence of astigmatism was 8.0%. The mean absolute spherical equivalent was 0.841D and 0.853D for right and left eye respectively. The number of participants with sight loss (as defined by VA= 6/12-6/60 in the better-seeing eye) was 27.0% in comparison to 0.89% and 1.1% in the general Cardiff and Wales population respectively (p-value is < 0.05). Additionally, 1.0% of the homeless subjects were registered blind (VA less than 3/60), in comparison to 0.17% for the national consensus after age standardization. Most participants had good knowledge regarding access to prescription glasses and eye examination services. Despite this, 85.0% never had their eyes examined by a doctor and 73.0% had their last optometrist appointment in more than 5 years. These findings suggested that there was a significant disparity in ocular health, including visual acuity and refractive error amongst the homeless in comparison to the general population. Further, the homeless were less likely to receive the same level of support and continued care in the community due to access barriers. These included a number of socio-economic factors such as travel expenses and regional availability of services, as well as administrative shortcomings. In conclusion, this research demonstrated unmet visual health needs within the homeless, and that inclusive policy changes may need to be implemented for better healthcare outcomes within this marginalized community.

Keywords: homelessness, refractive error, visual disability, Wales

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Authors: Ahmet Kurnaz, Eyup Yurt, Ümit Çiftci

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In this study, too, an attempt was made to reveal the place and effects of information technologies on the lives and education of gifted children based on the views of gifted. To this end, the effects of information technologies on gifted are general skills, technology use, academic and social skills, and cooperative and personal skills were investigated. These skills were explored depending on whether or not gifted had their own computers, had internet connection at home, or how often they use the internet, average time period they spent at the computer, how often they played computer games and their use of social media. The study was conducted using the screening model with a quantitative approach. The sample of the study consisted of 129 gifted attending 5-12th classes in 12 provinces in different regions of Turkey. 64 of the participants were female while 65 were male. The research data were collected using the using computer of gifted and information technologies (UCIT) questionnaire which was developed by the researchers and given its final form after receiving expert view. As a result of the study, it was found that UCIT use improved foreign language speaking skills of gifted, enabled them to get to know and understand different cultures, and made use of computer and information technologies while they study. At the end of the study these result were obtained: Gifted have positive idea using computer and communication technology. There are differences whether using the internet about the ideas UCIT. But there are not differences whether having computer, inhabited city, grade level, having internet at home, daily and weekly internet usage durations, playing the computer and internet game, having Facebook and Twitter account about the UCIT. UCIT contribute to the development of gifted vocabulary, allows knowing and understand different cultures, developing foreign language speaking skills, gifted do not give up computer when they do their homework, improve their reading, listening, understanding and writing skills in a foreign language. Gifted children want to have transition to the use of tablets in education. They think UCIT facilitates doing their homework, contributes learning more information in a shorter time. They'd like to use computer-assisted instruction programs at courses. They think they will be more successful in the future if their computer skills are good. But gifted students prefer teacher instead of teaching with computers and they said that learning can be run from home without going to school.

Keywords: gifted, using computer, communication technology, information technologies

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Authors: Anthony J. Kondracki, Bonzo I. Reddick, Jennifer L. Barkin

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We sought to examine the association of maternal Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and treponema pallidum (TP) (syphilis) infections with preterm birth (PTB) (<37 weeks gestation), low birth weight (LBW) (<2500 grams) and prenatal care (PNC) attendance. This cross-sectional study was based on data drawn from the 2020 United States National Center for Health Statistics (NCHS) Natality File. We estimated the prevalence of all births, early/late PTBs, moderately/very LBW, and the distribution of sexually transmitted infections (STIs) according to maternal characteristics in the sample. In multivariable logistic regression models, we examined adjusted odds ratios (aORs) and their corresponding 95% confidence intervals (CIs) of PTB and LBW subcategories in the association with maternal/infant characteristics, PNC status, and maternal CT, NG, and TP infections. In separate logistic regression models, we assessed the risk of these newborn outcomes stratified by PNC status. Adjustments were made for race/ethnicity, age, education, marital status, health insurance, liveborn parity, previous preterm birth, gestational hypertension, gestational diabetes, PNC status, smoking, and infant sex. Additionally, in a sensitivity analysis, we assessed the association with early, full, and late term births and the potential impact of unmeasured confounding using the E-value. CT (1.8%) was most prevalent STI in pregnancy, followed by NG (0.3%), and TP (0.1%). Non-Hispanic Black women, 20-24 years old, with a high school education, and on Medicaid had the highest rate of STIs. Around 96.6% of women reported receiving PNC and about 60.0% initiated PNC early in pregnancy. PTB and LBW were strongly associated with NG infection (12.2% and 12.1%, respectively) and late initiation/no PNC (8.5% and 7.6%, respectively), and ≤10 prenatal visits received (13.1% and 10.3%, respectively). The odds of PTB and LBW were 2.5- to 3-foldhigher for each STI among women who received ≤10 prenatal visits than >10 visits. Adequate prenatal care utilization and timely screening and treatment of maternal STIs can substantially reduce the burden of adverse newborn outcomes.

Keywords: low birthweight, prenatal care, preterm birth, sexually transmitted infections

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Authors: Ali Ghorbanipour

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The aim of this study is to investigate the drug resistance pattern and the value of the MIC (minimum inhibitory concentration)method to reduce the impact of infectious diseases and the slow development of resistance. Method: The study was conducted on clinical specimens collected between 2018 to 2021. identification of isolates and antibiotic susceptibility testing were performed using conventional biochemical tests. Antibiotic resistance was determined using kibry-Bauer disk diffusion and MIC by E-test methods comparative with microdilution plate elisa method. Results were interpreted according to CLSI. Results: Out of 249600 different clinical specimens, 18720 different pathogenic bacteria by overall detection ratio 7.7% were detected. Among pathogen bacterial were Gram negative bacteria (70%,n=13000) and Gram positive bacteria(30%,n=5720).Medically relevant gram-negative bacteria include a multitude of species such as E.coli , Klebsiella .spp , Pseudomonas .aeroginosa , Acinetobacter .spp , Enterobacterspp ,and gram positive bacteria Staphylococcus.spp , Enterococcus .spp , Streptococcus .spp was isolated . Conclusion: Our results highlighted that the resistance ratio among Gram Negative bacteria and Gram positive bacteria with different infection is high it suggest constant screening and follow-up programs for the detection of antibiotic resistance and the value of MIC drug susceptibility reporting that provide a new way to the usage of resistant antibiotic in combination with other antibiotics or accurate weight of antibiotics that inhibit or kill bacteria. Evaluation of wrong medication in the expansion of resistance and side effects of over usage antibiotics are goals. Ali ghorbanipour presently working as a supervision at the microbiology department of Massoud medical laboratory. Iran. Earlier, he worked as head department of pulmonary infection in firoozgarhospital, Iran. He received master degree in 2012 from Fergusson College. His research prime objective is a biologic wound dressing .to his credit, he has Published10 articles in various international congresses by presenting posters.

Keywords: antimicrobial profile, MIC & MBC Method, microplate antimicrobial assay, E-test

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Authors: Thyagi Ponnamperuma

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Background: Comorbidity between posttraumatic stress disorder (PTSD) and other psychological problems is common. Recent studies focused to investigate the underlying relationship between PTSD and comorbid psychopathologies. Among adolescents, higher rates of emotional and behavioral problems (EBP) have been reported following trauma, often coexisted with PTSD. The current study, thus, examined the relationship of posttraumatic stress symptoms to EBP in adolescents exposed to a variety of traumatic events. Further, the study investigated the relationship of trauma and comorbid PTSS to the self-perceived negative impact of EBP on daily functioning. Methods: Participants were 729 Sri Lankan adolescents (age 12 to 16 years; 54.9% female) living in areas impacted in varying degrees by the 2004 tsunami. In 2008, school-based screening was conducted and completed measures of, trauma exposure, PTSS, EBP, and related functional impairment. Results: Participants reported a high prevalence of trauma exposure (n = 438), including interpersonal violence (n = 155). DSM-IV criteria for full or partial PTSD were met by 23.7% of the trauma-exposed sample. Across all participants, 13.4% and 16.7% displayed clinically relevant levels of EBP and functional impairment, respectively. Among the trauma-exposed, 7% met criteria for both EBP and PTSD. EBP total scores and caseness were significantly higher in trauma-exposed adolescents with PTSD than in either those without PTSD or the non-traumatized control group. In subscale analysis, higher prevalence of serious emotional, conduct, and hyperactivity problems were reported in the PTSD positive group; the PTSD negative group did not differ significantly from the control group on any of the problem scales. In regression analyses, PTSS (β = .28, p < .001) and interpersonal violence (β = .13, p = .033) were significant predictors of EBP, cumulative trauma (β = .11, p = .076) showed no significant effect. Further, PTSS exacerbated the impact of EBP on daily functioning (β = 0.29, p = .023). Conclusion: PTSS were closely linked to EBP in adolescents, even years after the traumatic experience. PTSD and emotional and behavioral problems together pose a heightened risk for impaired daily functioning. Longitudinal studies are needed to clarify the causal pathway.

Keywords: adolescents, comorbidity, emotional and behavioral problems, functional impairment, posttraumatic stress, traumatic events

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Authors: Laura Mejias, Sandra Monteagudo, Oscar Martinez-Avila, Sergio Ponsa

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Bioplastics are gaining attention as potential substitutes of conventional fossil-derived plastics and new components of specialized applications in different industries. Besides, these constitute a sustainable alternative since they are biodegradable and can be obtained starting from renewable sources. Thus, agro-industrial wastes appear as potential substrates for bioplastics production using microorganisms, considering they are a suitable source for nutrients, low-cost, and available worldwide. Therefore, this approach contributes to the biorefinery and circular economy paradigm. The present study assesses the solid-state fermentation (SSF) technology for the co-synthesis of exopolysaccharides (EPS) and polyhydroxyalkanoates (PHA), two attractive biodegradable bioplastics, using the leftover of the brewery industry brewer's spent grain (BSG). After an initial screening of diverse PHA-producer bacteria, it was found that Burkholderia cepacia presented the highest EPS and PHA production potential via SSF of BSG. Thus, B. cepacia served to identify the most relevant aspects affecting the EPS+PHA co-synthesis at a lab-scale (100g). Since these are growth-dependent processes, they were monitored online through oxygen consumption using a dynamic respirometric system, but also quantifying the biomass production (gravimetric) and the obtained products (EtOH precipitation for EPS and solid-liquid extraction coupled with GC-FID for PHA). Results showed that B. cepacia has grown up to 81 mg per gram of dry BSG (gDM) at 30°C after 96 h, representing up to 618 times higher than the other tested strains' findings. Hence, the crude EPS production was 53 mg g-1DM (2% carbohydrates), but purity reached 98% after a dialysis purification step. Simultaneously, B. cepacia accumulated up to 36% (dry basis) of the produced biomass as PHA, mainly composed of polyhydroxybutyrate (P3HB). The maximum PHA production was reached after 48 h with 12.1 mg g⁻¹DM, representing threefold the levels previously reported using SSF. Moisture content and aeration strategy resulted in the most significant variables affecting the simultaneous production. Results show the potential of co-synthesis via SSF as an attractive alternative to enhance bioprocess feasibility for obtaining these bioplastics in residue-based systems.

Keywords: bioplastics, brewer’s spent grain, circular economy, solid-state fermentation, waste to product

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Authors: C. Hernandez-Garcia, P. Adderley, D. Bullard, J. Grames, M. A. Mamun, G. Palacios-Serrano, M. Poelker, M. Stutzman, R. Suleiman, Y. Wang, , S. Zhang

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High-energy nuclear physics experiments performed at the Jefferson Lab (JLab) Continuous Electron Beam Accelerator Facility require a beam of spin-polarized ps-long electron bunches. The electron beam is generated when a circularly polarized laser beam illuminates a GaAs semiconductor photocathode biased at hundreds of kV dc inside an ultra-high vacuum chamber. The photocathode is mounted on highly polished stainless steel electrodes electrically isolated by means of a conical-shape ceramic insulator that extends into the vacuum chamber, serving as the cathode electrode support structure. The assembly is known as a dc photogun, which has to simultaneously meet the following criteria: high voltage to manage space charge forces within the electron bunch, ultra-high vacuum conditions to preserve the photocathode quantum efficiency, no field emission to prevent gas load when field emitted electrons impact the vacuum chamber, and finally no voltage breakdown for robust operation. Over the past decade, JLab has tested and implemented the use of inverted geometry ceramic insulators connected to commercial high voltage cables to operate a photogun at 200kV dc with a 10 cm long insulator, and a larger version at 300kV dc with 20 cm long insulator. Plans to develop a third photogun operating at 400kV dc to meet the stringent requirements of the proposed International Linear Collider are underway at JLab, utilizing even larger inverted insulators. This contribution describes approaches that have been successful in solving challenging problems related to breakdown and field emission, such as triple-point junction screening electrodes, mechanical polishing to achieve mirror-like surface finish and high voltage conditioning procedures with Kr gas to extinguish field emission.

Keywords: electron guns, high voltage techniques, insulators, vacuum insulation

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Authors: Jolene M. Helena, Annie M. Joubert, Peace Mabeta, Magdalena Coetzee, Roy Lakier, Anne E. Mercier

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Targeting the distant tumour and its microenvironment whilst preserving bone density is important in improving the outcomes of patients with bone metastases. 2-Ethyl-3-O-sulphamoyl-estra1,3,5(10)16-tetraene (ESE-16) is an in-silico-designed 2- methoxyestradiol analogue which aimed at enhancing the parent compound’s cytotoxicity and providing a more favourable pharmacokinetic profile. In this study, the potential radiosensitization effects of ESE-16 were investigated in an in vitro bone metastasis model consisting of murine pre-osteoblastic (MC3T3-E1) and pre-osteoclastic (RAW 264.7) bone cells, metastatic prostate (DU 145) and breast (MDA-MB-231) cancer cells, as well as human umbilical vein endothelial cells (HUVECs). Cytotoxicity studies were conducted on all cell lines via spectrophotometric quantification of 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide. The experimental set-up consisted of flow cytometric analysis of cell cycle progression and apoptosis detection (Annexin V-fluorescein isothiocyanate) to determine the lowest ESE-16 and radiation doses to induce apoptosis and significantly reduce cell viability. Subsequent experiments entailed a 24-hour low-dose ESE-16-exposure followed by a single dose of radiation. Termination proceeded 2, 24 or 48 hours thereafter. The effect of the combination treatment was investigated on osteoclasts via tartrate-resistant acid phosphatase (TRAP) activity- and actin ring formation assays. Tumour cell experiments included investigation of mitotic indices via haematoxylin and eosin staining; pro-apoptotic signalling via spectrophotometric quantification of caspase 3; deoxyribonucleic acid (DNA) damage via micronuclei analysis and histone H2A.X phosphorylation (γ-H2A.X); and Western blot analyses of bone morphogenetic protein-7 and matrix metalloproteinase-9. HUVEC experiments included flow cytometric quantification of cell cycle progression and free radical production; fluorescent examination of cytoskeletal morphology; invasion and migration studies on an xCELLigence platform; and Western blot analyses of hypoxia-inducible factor 1-alpha and vascular endothelial growth factor receptor 1 and 2. Tumour cells yielded half-maximal growth inhibitory concentration (GI50) values in the nanomolar range. ESE-16 concentrations of 235 nM (DU 145) and 176 nM (MDA-MB-231) and a radiation dose of 4 Gy were found to be significant in cell cycle and apoptosis experiments. Bone and endothelial cells were exposed to the same doses as DU 145 cells. Cytotoxicity studies on bone cells reported that RAW 264.7 cells were more sensitive to the combination treatment than MC3T3-E1 cells. Mature osteoclasts were more sensitive than pre-osteoclasts with respect to TRAP activity. However, actin ring morphology was retained. The mitotic arrest was evident in tumour and endothelial cells in the mitotic index and cell cycle experiments. Increased caspase 3 activity and superoxide production indicated pro-apoptotic signalling in tumour and endothelial cells. Increased micronuclei numbers and γ-H2A.X foci indicated increased DNA damage in tumour cells. Compromised actin and tubulin morphologies and decreased invasion and migration were observed in endothelial cells. Western blot analyses revealed reduced metastatic and angiogenic signalling. ESE-16-induced radiosensitization inhibits metastatic signalling and tumour cell survival whilst preferentially preserving bone cells. This low-dose combination treatment strategy may promote the quality of life of patients with metastatic bone disease. Future studies will include 3-dimensional in-vitro and murine in-vivo models.

Keywords: angiogenesis, apoptosis, bone metastasis, cancer, cell migration, cytoskeleton, DNA damage, ESE-16, radiosensitization.

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Authors: Muhammad Shahid Shah, Akram Maqbool, Samina Ashraf

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Since start of this century, world has adopted inclusion as a trend in special education. To meet the challenges of inclusion response, the Punjab government has developed a progressive policy to implement inclusive education. The objectives of this research were to analyze the administration and implementation process by consideration on the management, student’s admission process, screening and assessment, adaptations in curriculum and instruction along with an evaluation, government and nonprofit organizations support. The sample consisted of 50 schools both public and private with a total of 3000 students, 9 percent of which (270) were students with disabilities. Among all the students with disabilities, 63 percent (170) were male and 37 percent (100) were female. The concluded remarks regarding management revealed that a large number of inclusive schools was lacking in terms of developing a certain model for inclusion, including the managerial breakup of staff, the involvement of stakeholders, and conducted frequent meetings. Many of schools are not able to restructure their school organizations due to lack of financial resources, consultations, and backup. As for as student’s admission/identification/assessment was concerned, only 12 percent schools applied a selection process regarding student admission, half of which used different procedures for disable candidates. Approximately 5 percent of inclusive schools had modified their curriculum, including a variety of standards. In terms of instruction, 25 percent of inclusive schools reported that they modified their instructional process. Only a few schools, however, provided special equipment for students with visual impairment, physical impairment, speech and hearing problems, students with mild intellectual disabilities, and autism. In a student evaluation, more than 45 percent reported that test items, administration, time allocations, and students’ reports were modified. For the primary board examination conducted by the Education Department of Government of Punjab, this number decreased dramatically. Finally, government and nonprofit organizations support in the forms of funding, coaching, and facilities were mostly provided by provincial governments and by Ghazali Education Trust.

Keywords: inclusion, identification, assessment, funding, facilities, evaluation

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Authors: Maria Bonolo Mathevula

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Background: Children are important members of communities playing major role in the future of any given country (Pera, Fails, Gelsomini, &Garzotto, 2018). Visual Perceptual Skills (VPSs) in children are important health aspect of early childhood development through the Foundation Phases in school. Subsequently, children should undergo visual screening before commencement of schooling for early diagnosis ofVPSs anomalies because the primary role of VPSs is to capacitate children with academic performance in general. Aim : The aim of this study was to determine the anomalies of visual VPSs amongst school children in Foundation Phase. The study’s objectives were to determine the prevalence of VPSs anomalies amongst school children in Foundation Phase; Determine the relationship between children’s academic and VPSs anomalies; and to investigate the relationship between VPSs anomalies and refractive error. Methodology: This study was a mixed method whereby triangulated qualitative (interviews) and quantitative (questionnaire and clinical data) was used. This was, therefore, descriptive by nature. The study’s target population was school children in Foundation Phase. The study followed purposive sampling method. School children in Foundation Phase were purposively sampled to form part of this study provided their parents have given a signed the consent. Data was collected by the use of standardized interviews; questionnaire; clinical data card, and TVPS standard data card. Results: Although the study is still ongoing, the preliminary study outcome based on data collected from one of the Foundation Phases have suggested the following:While VPSs anomalies is not prevalent, it, however, have indirect relationship with children’s academic performance in Foundation phase; Notably, VPSs anomalies and refractive error are directly related since majority of children with refractive error, specifically compound hyperopic astigmatism, failed most subtests of TVPS standard tests. Conclusion: Based on the study’s preliminary findings, it was clear that optometrists still have a lot to do in as far as researching on VPSs is concerned. Furthermore, the researcher recommends that optometrist, as the primary healthcare professionals, should also conduct the school-readiness pre-assessment on children before commencement of their grades in Foundation phase.

Keywords: foundation phase, visual perceptual skills, school children, refractive error

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Authors: Anjana Aggarwal, Sheilja Walia

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Prevalence of obesity and overweight is increasing due to sedentary lifestyles and busy schedules of people that spend less time on physical exercise. To reduce weight, people are finding easier and more convenient ways. The easiest solution is the use of dietary supplements and fat burners. These are products that decrease body weight by increasing the basal metabolic rate. Various reports have been published on the consumption of fat burners leading to heart palpitations, seizures, anxiety, depression, psychosis, bradycardia, insomnia, muscle contractions, hepatotoxicity, and even liver failure. Case reports and series are reporting that the ingredients present in the fat burners caused acute liver failure (ALF) and hepatic toxicity in many cases. Another contributing factor is the absence of regulations from the Food and Drug Administration on these products, leading to increased consumption and a higher risk of liver diseases among the population. This systematic review aims to attain a better understanding of the dietary supplements used globally to reduce weight and document the case reports/series of acute liver failure caused by the consumption of fat burners. Electronic databases like PubMed, Cochrane, Google Scholar, etc., will be systematically searched for relevant articles. Various websites of dietary products and brands that sell such supplements, Journals of Hepatology, National and international projects launched for ALF, and their reports, along with the review of grey literature, will also be done to get a better understanding of the topic. After discussing with the co-author, the selection and screening of the articles will be performed by the author. The studies will be selected based on the predefined inclusion and exclusion criteria. The case reports and case series that will be included in the final list of the studies will be assessed for methodological quality using the CARE guidelines. The results from this study will provide insights and a better understanding of fat burners. Since the supplements are easily available in the market without any restrictions on their sale, people are unaware of their adverse effects. The consumption of these supplements causes acute liver failure. Thus, this review will provide a platform for future larger studies to be conducted.

Keywords: acute liver failure, dietary supplements, fat burners, weight loss supplements

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Authors: Najia Zulfiqar

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Imparting moral education is the need of time, considering the obvious moral decline in society. Recent research shows the downfall of moral competence among university students. The main objective of the present study was to develop moral development intervention strategies for undergraduate students of Sports and Physical Education. Using an interpretative phenomenological approach, insight into field-specific moral issues was gained through interviews with 7 subject experts and a focus-group discussion session with 8 students. Two research assistants who were trained in qualitative interviewing collected, transcribed and analyzed data into the MAXQDA software using content and discourse analyses. The identified moral issues in Sports and Physical Education were sports gambling and betting, pay-for-play, doping, coach misconduct, tampering, cultural bias, gender equity/nepotism, bullying/discrimination, and harassment. Next, intervention modules were developed for each moral issue based on hypothetical situations, and followed by guided reflection and dilemma discussion questions. The third moral development strategy was community services that included posture screening, diet plan for different age groups, open fitness ground training, exercise camps for physical fitness, balanced diet awareness camp, gymnastic camp, shoe assessment as per health standards, and volunteering for public awareness at the playground, gymnasium, stadium, park, etc. The intervention modules were given to four subject specialists for expert validation who were from different backgrounds within Sport Sciences. Upon refinement and finalization, four students were presented with these intervention modules and questioned about accuracy, relevance, comprehension, and content organization. Iterative changes were made in the content of the intervention modules to tailor them to the moral development needs of undergraduate students. This intervention will strengthen positive moral values and foster mature decision-making about right and wrong acts. As this intervention is easy to apply as a remedial tool, academicians and policymakers can use this to promote students’ moral development.

Keywords: community service, dilemma discussion, morality, physical education, university students.

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Authors: Igor Jerkovic

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Owing to the attractive sensory properties and low odour thresholds, norisoprenoids (degraded carotenoid-like structures with 3,5,5-trimethylcyclohex-2-enoic unit) have been identified as aroma contributors in a number of different matrices. C₁₃-Norisoprenoids have been found among volatile organic compounds of various honey types as well as C₉//C₁₀-norisoprenoids or C₁₄/C₁₅-norisoprenoids. Besides degradation of abscisic acid (which produces, e.g., dehydrovomifoliol, vomifoliol, others), the cleavage of the C(9)=C(10) bond of other carotenoid precursors directly generates nonspecific C₁₃-norisoprenoids such as trans-β-damascenone, 3-hydroxy-trans-β-damascone, 3-oxo-α-ionol, 3-oxo-α-ionone, β-ionone found in various honey types. β-Damascenone and β-ionone smelling like honey, exhibit the lowest odour threshold values of all C₁₃-norisoprenoids. The presentation is targeted on two uncommon C₁₃-norisoprenoids in the honey flavor that could be used as specific or nonspecific chemical markers of the botanical origin. Namely, after screening of different honey types, the focus was directed on Centaruea cyanus L. and Allium ursinum L. honey. The samples were extracted by headspace solid-phase microextraction (HS-SPME) and ultrasonic solvent extraction (USE) and the extracts were analysed by gas chromatography and mass spectrometry (GC-MS). SPME fiber with divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) coating was applied for the research of C. cyanus honey headspace and predominant identified compound was 3,4-dihydro-3-oxoedulan (2,5,5,8a-tetramethyl-2,3,5,6,8,8a-hexahydro-7H-chromen-7-one also known as 2,3,5,6,8,8a-hexahydro-2,5,5,8a-tetramethyl-7H-1-benzo-pyran-7-one). The oxoedulan structure contains epoxide and it is more volatile in comparison with its hydroxylated precursors. This compound has not been found in other honey types and can be considered specific for C. cyanus honey. The dichloromethane extract of A. ursinum honey contained abundant (E)-4-(r-1',t-2',c-4'-trihydroxy-3',6',6'-trimethylcyclohexyl)-but-3-en-2-one that was previously isolated as dominant substance from the ether extracts of New Zealand thyme honey. Although a wide variety of degraded carotenoid-like substances have been identified from different honey types, this appears to be rare situation where 3,4-dihydro-3-oxoedulan and (E)-4-(r-1',t-2',c-4'-trihydroxy-3',6',6'-trimethylcyclohexyl)-but-3-en-2-one have been found that is of great importance for chemical fingerprinting and identification of the chemical biomarkers that can complement the pollen analysis as the major method for the honey classification.

Keywords: 3, 4-dihydro-3-oxoedulan, (E)-4-(r-1', t-2', c-4'-trihydroxy-3', 6', 6'-trimethylcyclohexyl)-but-3-en-2-one, honey flavour, C₁₃-norisoprenoids

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Authors: Haoyu Zhao, Qianshu Ma, Min Xie, Yunqi Huang, Yunjia Liu, Huan Song, Hongsheng Gui, Mingli Li, Qiang Wang

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Rationale: Bipolar disorder (BD) and major depressive disorder (MDD), as severe chronic illnesses that restrict patients’ psychosocial functioning and reduce their quality of life, are both categorized into mood disorders. Emerging evidence has suggested that the reliability of self-rated health (SRH) was wellvalidated and that the risk of various health outcomes, including mortality and health care costs, could be predicted by SRH. Compared with other lengthy multi-item patient-reported outcomes (PRO) measures, SRH was proven to have a comparable predictive ability to predict mortality and healthcare utilization. However, to our knowledge, no study has been conducted to assess the association between SRH and hospitalization among people with mental disorders. Therefore, our study aims to determine the association between SRH and subsequent all-cause hospitalizations in patients with BD and MDD. Methods: We conducted a prospective cohort study on people with BD or MDD in the UK from 2006 to 2010 using UK Biobank touchscreen questionnaire data and linked administrative health databases. The association between SRH and 2-year all-cause hospitalizations was assessed using proportional hazard regression after adjustment for sociodemographics, lifestyle behaviors, previous hospitalization use, the Elixhauser comorbidity index, and environmental factors. Results: A total of 29,966 participants were identified, experiencing 10,279 hospitalization events. Among the cohort, the average age was 55.88 (SD 8.01) years, 64.02% were female, and 3,029 (10.11%), 15,972 (53.30%), 8,313 (27.74%), and 2,652 (8.85%) reported excellent, good, fair, and poor SRH, respectively. Among patients reporting poor SRH, 54.19% had a hospitalization event within 2 years compared with 22.65% for those having excellent SRH. In the adjusted analysis, patients with good, fair, and poor SRH had 1.31 (95% CI 1.21-1.42), 1.82 (95% CI 1.68-1.98), and 2.45 (95% CI 2.22, 2.70) higher hazards of hospitalization, respectively, than those with excellent SRH. Conclusion: SRH was independently associated with subsequent all-cause hospitalizations in patients with BD or MDD. This large study facilitates rapid interpretation of SRH values and underscores the need for proactive SRH screening in this population, which might inform resource allocation and enhance high-risk population detection.

Keywords: severe mental illnesses, hospitalization, risk prediction, patient-reported outcomes

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Authors: Mina Salamatmanesh, Elizabeth Fitzpatrick, Tim Ramsay, Josee Lagacé, Lindsey Sikora, JoAnne Whittingham

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Introduction: Hearing loss (HL) is one of the most common disorders that presents at birth and in early childhood. Universal newborn hearing screening (UNHS) has been adopted based on the assumption that with early identification of HL, children will have access to optimal amplification and intervention at younger ages, therefore, taking advantage of the brain’s maximal plasticity. One particular challenge for parents in the early years is achieving consistent hearing aid (HA) use which is critical to the child’s development and constitutes the first step in the rehabilitation process. This study examined the consistency of hearing aid use in young children based on data logging information documented during audiology sessions in the first three years after hearing aid fitting. Methodology: The first 100 children who were diagnosed with bilateral HL before 72 months of age since 2003 to 2015 in a pediatric audiology clinic and who had at least two hearing aid follow-up sessions with available data logging information were included in the study. Data from each audiology session (age of child at the session, average hours of use per day (for each ear) in the first three years after HA fitting) were collected. Clinical characteristics (degree of hearing loss, age of HA fitting) were also documented to further understanding of factors that impact HA use. Results: Preliminary analysis of the results of the first 20 children shows that all of them (100%) have at least one data logging session recorded in the clinical audiology system (Noah). Of the 20 children, 17(85%) have three data logging events recorded in the first three years after HA fitting. Based on the statistical analysis of the first 20 cases, the median hours of use in the first follow-up session after the hearing aid fitting in the right ear is 3.9 hours with an interquartile range (IQR) of 10.2h. For the left ear the median is 4.4 and the IQR is 9.7h. In the first session 47% of the children use their hearing aids ≤5 hours, 12% use them between 5 to 10 hours and 22% use them ≥10 hours a day. However, these children showed increased use by the third follow-up session with a median (IQR) of 9.1 hours for the right ear and 2.5, and of 8.2 hours for left ear (IQR) IQR is 5.6 By the third follow-up session, 14% of children used hearing aids ≤5 hours, while 38% of children used them ≥10 hours. Based on the primary results, factors like age and level of HL significantly impact the hours of use. Conclusion: The use of data logging information to assess the actual hours of HA provides an opportunity to examine the: a) challenges of families of young children with HAs, b) factors that impact use in very young children. Data logging when used collaboratively with parents, can be a powerful tool to identify problems and to encourage and assist families in maximizing their child’s hearing potential.

Keywords: hearing loss, hearing aid, data logging, hours of use

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Authors: Twinkle Sara Joseph

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Virtual reality technology has emerged as a revolutionary power that can transform the education sector in many ways. VR environments can break the boundaries of the traditional classroom setting by immersing the students in realistic 3D environments where they can interact with virtual characters without fearing being judged. Communication skills are essential for every profession, and studies suggest the importance of implementing basic-level communication courses at both the school and graduate levels. Interpersonal communication is a skill that gains prominence as it is required in every profession. Traditional means of training have limitations for trainees as well as participants. The fear of being judged, the audience interaction, and other factors can affect the performance of a participant in a traditional classroom setting. Virtual reality offers a unique opportunity for its users to participate in training that does not set any boundaries that prevent the participants from performing in front of an audience. Specialised applications designed in VR headsets offer a range of training and exercises for participants without any time, space, or audience limitations. The present study aims at measuring the effectiveness of VR training in improving interpersonal communication skills among students. The study uses a mixed-method approach, in which a pre-and post-test will be designed to measure effectiveness. A preliminary selection process involving a questionnaire and a screening test will identify suitable candidates based on their current communication proficiency levels. Participants will undergo specialised training through the VR application Virtual Speech tailored for interpersonal communication and public speaking, designed to operate without the traditional constraints of time, space, or audience. The training's impact will subsequently be measured through situational exercises to engage the participants in interpersonal communication tasks, thereby assessing the improvement in their skills. The significance of this study lies in its potential to provide empirical evidence supporting VR technology's role in enhancing communication skills, thereby offering valuable insights for integrating VR-based methodologies into educational frameworks to prepare students more effectively for their professional futures.

Keywords: virtual reality, VR training, interpersonal communication, communication skills, 3D environments

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Authors: Maznieda Mahjom, Rohaida Ismail, Masita Arip, Mohd Shaiful Azlan, Nor’Ashikin Othman, Hafizah Abdullah, nor Zahrin Hasran, Joshita Jothimanickam, Syaqilah Shawaluddin, Nadia Mohamad, Raheel Nazakat, Tuan Mohd Amin, Mizanurfakhri Ghazali, Rosmanajihah Mat Lazim

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COVID-19 outbreak is particularly detrimental to the mental health of everyone as well as leaving a long devastating crisis in the healthcare sector. Daily increment of COVID-19 cases and close contact, necessitating the testing of a large number of samples, thus increasing the workload and burden to laboratory personnel. This study aims to determine the prevalence of personal-, work- and client-related burnout as well as to measure the concentration of salivary cortisol among laboratory personnel in the main laboratories in Klang Valley, Malaysia. This cross-sectional study was conducted in late 2021 and recruited a total of 404 respondents from three laboratories in Klang Valley, Malaysia. The level of burnout was assessed using Copenhagen Burnout Inventory (CBI) comprising three sub-dimensions of personal-, work- and client-related burnout. The cut-off score of 50% and above indicated possible burnout. Meanwhile, salivary cortisol was measured using a competitive enzyme immunoassay kit (Salimetrics, State College, PA, USA). Normal levels of salivary cortisol concentration in adults are within 0.094 to 1.551 μg/dl (morning) and can be none detected to 0.359 μg/dl (evening). The prevalence of personal-, work- and client-related burnout among laboratory personnel were 36.1%, 17.8% and 7.2% respectively. Meanwhile, the abnormal morning and evening cortisol concentration recorded were 29.5% and 21.8% excluding 6.9%-7.4% missing data. While the IgA level is normal for most of the respondents, which recorded at 95.53%. Laboratory personnel were at risk of suffering burnout during the COVID-19 pandemic. Thus, mental health programs need to be addressed at the department and hospital level by regularly screening healthcare workers and designing an intervention program. It is also vital to improve the coping skills of laboratory personnel by increasing the awareness of good coping skill techniques. The training must be in an innovative way to ensure that the lab personnel can internalise the technique and practise it in real life.

Keywords: burnout, COVID-19, laborotary personnel, salivary cortisol

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Authors: Rhea Khosla, Victoria Tzortziou-Brown

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Introduction: Adolescent SRH has been neglected since the start of the millennium. Adolescents comprise 16% of the global population, with the largest proportion living in Asia (650 million). By late adolescence, individuals in these regions are likely to become sexually active, and thus they must understand their SRH rights. Many lack knowledge of SRH, using unreliable sources for such information. Sex education is necessary to standardize and inform sexual knowledge, which empowers adolescents to make informed SRH decisions. School is an appropriate environment for this, however, SRH education requires effective policy to enforce. Nonetheless, this issue remains of low political priority in Asia and Africa. Current literature on sex education policy in schools in these regions is scarce and tends to have broad aims. Thus, a scoping review was necessary. Methods: Literature searches were conducted in February 2023 using six databases, including grey literature databases (PubMed, Scopus, Embase, Web of Science, Google Scholar, Global Index Medicus), returning a total of 1537 unique articles. After screening titles, abstracts and full text, 17 articles remained. References of included articles were additionally searched, producing a further 7 articles, which then underwent thematic analysis Results: Most countries in Africa and Asia did not have studies on this topic. Studies derived data from interviews with key stakeholders and quantitative methods quantified questionnaire responses. Barriers were: policy/curriculum issues, societal opinions, teaching discomfort, and lack of educator training. Limitations were insufficient timing, inconsistent implementation, insufficient hours dedicated to teaching, education received late into schooling, and discrepancies between teachers, schools, and students about whether policies were being implemented. Discussion: Based on the existing limited evidence, a cultural shift to reduce stigma seems necessary, alongside teacher and student involvement in policy formulation with effective implementation monitoring and educator training.

Keywords: adolescent, Africa, Asia, education, sexual and reproductive health, policy

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Authors: Fatima Mohammed Musa, J. B. Ameh, S. A. Ado, O. S. Olonitola

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The study was undertaken to evaluate the phytochemical constituents of extracts of Terminalia avicennioides leaf and the antidiarrhoeal effect of n-butanol fraction of the leaf extract in Swiss albino rats infected with Salmonella Typhimurium and Escherichia coli. Ethanol crude extract of Terminalia avicennioides leaf was dissolved in 1.5 liters of sterile distilled water. The extract solution was partitioned with 250 ml each of chloroform, ethyl acetate and n-butanol solvents (1:1v/v) to obtain soluble fractions from the extract. The leaf extract and its fractions were screened for the presence of phytocompounds using standard analytical methods. The antidirrhoeal activity of n-butanol fraction was evaluated in Swiss albino rats using standard methods. The results of phytochemical screening of extract of Terminalia avicennioides leaf and its fractions, revealed the presence of carbohydrates, alkaloids, tannins, flavonoids, saponins, steroids, triterpens, glycosides and phenols. The results of in vivo activity showed that 60 % of each group of rats infected with 2.0 x 108 cfu/ml viable cells of S. Typhimurium and 2.0 x109 cfu/ml viable cells of E. coli manifested the symptoms of diarrhoea, 72 hours after the rats were challenged with bacteria. Other symptoms observed among the infected animals included, loss of appetite, loss of weight, general body weakness and 40 % mortality in S. Typhimurium infected non treated group of rats. Similarly, 60 %, and 20 % mortality was observed among E. coli infected none treated and E. coli infected antibiotic (metronidazole) treated groups of rats respectively. However, there was a reduction in the number of infected rats defecating watery stools over time among all the infected rats that were treated with n-butanol fraction of the leaf extract and mortality was also not observed in the group, indicating high efficacy of n-butanol fraction of T. avicennioides leaf. The results also indicated that n-butanol can be used as alternative source of antidiarrhoeal agent in the treatment of diarrhoea caused by Salmonella Typhimurium and Escherichia coli. In the light of this, there is a need for further research on the mechanism of action of the candidate fraction of T. avicennioides leaf which could be responsible for the observed in vivo antibacterial activity.

Keywords: antidirrhoeal effect, phytochemical constituents, swiss albino rats, terminalia avicennioides

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Authors: Andrew Freiburger, Sergi Molins

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Freshwater is a vital resource; yet, the supply of clean freshwater is diminishing as the consequence of melting snow and ice from global warming, pollution from industry, and an increasing demand from human population growth. The unsustainable trajectory of diminishing water resources is projected to jeopardize water security for billions of people in the 21st century. Membrane desalination technologies may resolve the growing discrepancy between supply and demand by filtering arbitrary feed water into a fraction of renewable, clean water and a fraction of highly concentrated brine. The leading hindrance of membrane desalination is fouling, whereby the highly concentrated brine solution encourages micro-organismal colonization and/or the precipitation of occlusive minerals (i.e. scale) upon the membrane surface. Thus, an understanding of brine formation is necessary to mitigate membrane fouling and to develop efficacious desalination technologies that can bolster the supply of available freshwater. This study presents a reactive transport simulation of brine formation and scale deposition during reverse osmosis (RO) desalination. The simulation conceptually represents the RO module as a one-dimensional domain, where feed water directionally enters the domain with a prescribed fluid velocity and is iteratively concentrated in the immobile layer of a dual porosity model. Geochemical PHREEQC code numerically evaluated the conceptual model with parameters for the BW30-400 RO module and for real water feed sources – e.g. the Red and Mediterranean seas, and produced waters from American oil-wells, based upon peer-review data. The presented simulation is computationally simpler, and hence less resource intensive, than the existent and more rigorous simulations of desalination phenomena, like TOUGHREACT. The end-user may readily prepare input files and execute simulations on a personal computer with open source software. The graphical results of fouling-potential and brine characteristics may therefore be particularly useful as the initial tool for screening candidate feed water sources and/or informing the selection of an RO module.

Keywords: desalination, PHREEQC, reactive transport, scaling

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Authors: Lien Gysens, Bert Vanmechelen, Maarten Haspeslagh, Piet Maes, Ann Martens

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Bovine papillomavirus (BPV) types 1 and 2 play a central role in the etiology of the most common neoplasm in horses, the equine sarcoid. The unknown mechanism behind the unique variety in a clinical presentation on the one hand and the host-dependent clinical outcome of BPV-1 infection, on the other hand, indicate the involvement of additional factors. Earlier studies have reported the potential functional significance of intratypic sequence variants, along with the existence of sarcoid-sourced BPV variants. Therefore, intratypic sequence variation seems to be an important emerging viral factor. This study aimed to give a broad insight in sarcoid-sourced BPV variation and explore its potential association with disease presentation. In order to do this, a nanopore sequencing approach was successfully optimized for screening a wide spectrum of clinical samples. Specimens of each tumour were initially screened for BPV-1/-2 by quantitative real-time PCR. A custom-designed primer set was used on BPV-positive samples to amplify the complete viral genome in two multiplex PCR reactions, resulting in a set of overlapping amplicons. For phylogenetic analysis, separate alignments were made of all available complete genome sequences for BPV-1/-2. The resulting alignments were used to infer Bayesian phylogenetic trees. We found substantial genetic variation among sarcoid-derived BPV-1, although this variation could not be linked to disease severity. Several of the BPV-1 genomes had multiple major deletions. Remarkably, the majority of the cluster within the region coding for late viral genes. Together with the extensiveness (up to 603 nucleotides) of the described deletions, this suggests an altered function of L1/L2 in disease pathogenesis. By generating a significant amount of complete-length BPV genomes, we succeeded in introducing next-generation sequencing into veterinary research focusing on the equine sarcoid, thus facilitating the first report of both nanopore-based sequencing of complete sarcoid-sourced BPV-1/-2 and the simultaneous nanopore sequencing of multiple complete genomes originating from a single clinical sample.

Keywords: Bovine papillomavirus, equine sarcoid, horse, nanopore sequencing, phylogenetic analysis

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Authors: Neslihan Demirci, Serdar Durdağı

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Mycobacterium tuberculosis is still a worldwide disease-causing agent that, according to WHO, led to the death of 1.5 million people from tuberculosis (TB) in 2020. The bacteria reside in macrophages located specifically in the lung. There is a known quadruple drug therapy regimen for TB consisting of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Over the past 60 years, there have been great contributions to treatment options, such as recently approved delamanid (OPC67683) and bedaquiline (TMC207/R207910), targeting mycolic acid and ATP synthesis, respectively. Also, there are natural compounds that can block the tryptophanyl-tRNA synthetase (TrpRS) enzyme, chuangxinmycin, and indolmycin. Yet, already the drug resistance is reported for those agents. In this study, the newly released TrpRS enzyme structure is investigated for potential inhibitor drugs from already synthesized molecules to help the treatment of resistant cases and to propose an alternative drug for the quadruple drug therapy of tuberculosis. Maestro, Schrodinger is used for docking and molecular dynamic simulations. In-house library containing ~8000 compounds among FDA-approved indole-containing compounds, a total of 57 obtained from the ChemBL were used for both ATP and tryptophan binding pocket docking. Best of indole-containing 57 compounds were subjected to hit expansion and compared later with virtual screening workflow (VSW) results. After docking, VSW was done. Glide-XP docking algorithm was chosen. When compared, VSW alone performed better than the hit expansion module. Best scored compounds were kept for ten ns molecular dynamic simulations by Desmond. Further, 100 ns molecular dynamic simulation was performed for elected molecules according to Z-score. The top three MMGBSA-scored compounds were subjected to steered molecular dynamic (SMD) simulations by Gromacs. While SMD simulations are still being conducted, ponesimod (for multiple sclerosis), vilanterol (β₂ adrenoreceptor agonist), and silodosin (for benign prostatic hyperplasia) were found to have a significant affinity for tuberculosis TrpRS, which is the propulsive force for the urge to expand the research with in vitro studies. Interestingly, top-scored ponesimod has been reported to have a side effect that makes the patient prone to upper respiratory tract infections.

Keywords: drug repurposing, molecular dynamics, tryptophanyl-tRNA synthetase, tuberculosis

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Authors: Salina Yahya Saddick

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Ovarian cancer remains the most lethal gynecological malignancy due to the lack of highly sensitive and specific screening tools for detection of early-stage disease. The OSE provides the progenitor cells for 90% of human ovarian cancers. Recent morphologic, immunohistochemical and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer (EOC) based on a ualistic model of carcinogenesis that divides EOC into two broad categories designated Types I and II which are characterized by specific mutations, including KRAS, BRAF, ERBB2, CTNNB1, PTEN PIK3CA, ARID1A, and PPPR1A, which target specific cell signaling pathways. Type 1 tumors rarely harbor TP53. type I tumors are relatively genetically stable and typically display a variety of somatic sequence mutations that include KRAS, BRAF, PTEN, PIK3CA CTNNB1 (the gene encoding beta catenin), ARID1A and PPP2R1A but very rarely TP53 . The cancer stem cell (CSC) hypothesis postulates that the tumorigenic potential of CSCs is confined to a very small subset of tumor cells and is defined by their ability to self-renew and differentiate leading to the formation of a tumor mass. Potential protein biomarker miRNA, are promising biomarkers as they are remarkably stable to allow isolation and analysis from tissues and from blood in which they can be found as free circulating nucleic acids and in mononuclear cells. Recently, genomic anaylsis have identified biomarkers and potential therapeutic targets for ovarian cancer namely, FGF18 which plays an active role in controlling migration, invasion, and tumorigenicity of ovarian cancer cells through NF-κB activation, which increased the production of oncogenic cytokines and chemokines. This review summarizes update information on epithelial ovarian cancers and point out to the most recent ongoing research.

Keywords: epithelial ovarian cancers, somatic sequence mutations, cancer stem cell (CSC), potential protein, biomarker, genomic analysis, FGF18 biomarker

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Authors: Vichayada Laohapiboolkul

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Introduction: As the legal use of cannabis is being widely accepted throughout the world, medical cannabis has been explored in order to become an alternative cure for patients. Tetrahydrocannabinol (THC) and Cannabidiol (CBD) are natural cannabinoids found in the Cannabis plant which is proved to have positive treatment for various diseases and symptoms such as chronic pain, neuropathic pain, spasticity resulting from multiple sclerosis, reduce cancer-associated pain, autism spectrum disorders (ASD), dementia, cannabis and opioid dependence, psychoses/schizophrenia, general social anxiety, posttraumatic stress disorder, anorexia nervosa, attention-deficit hyperactivity disorder, and Tourette's disorder. Regardless of all the medical benefits, THC, if not metabolized, can lead to mild up to severe adverse drug reactions (ADR). The enzyme CYP2C19 was found to be one of the metabolizers of THC. However, the suballele CYP2C19*2 manifests as a poor metabolizer which could lead to higher levels of THC than usual, possibly leading to various ADRs. Objective: The aim of this study was to investigate the distribution of CYP2C19, specifically CYP2C19*2, genes in Thai patients treated with medical cannabis along with adverse drug reactions. Materials and Methods: Clinical data and EDTA whole blood for DNA extraction and genotyping were collected from patients for this study. CYP2C19*2 (681G>A, rs4244285) genotyping was conducted using the Real-time PCR (ABI, Foster City, CA, USA). Results: There were 42 medical cannabis-induced ADRs cases and 18 medical cannabis tolerance controls who were included in this study. A total of 60 patients were observed where 38 (63.3%) patients were female and 22 (36.7%) were male, with a range of age approximately 19 - 87 years. The most apparent ADRs for medical cannabis treatment were dry mouth/dry throat (76.7%), followed by tachycardia (70%), nausea (30%) and a few arrhythmias (10%). In the total of 27 cases, we found a frequency of 18 CYP2C19*1/*1 alleles (normal metabolizers, 66.7%), 8 CYP2C19*1/*2 alleles (intermediate metabolizers, 29.6%) and 1 CYP2C19*2/*2 alleles (poor metabolizers, 3.7%). Meanwhile, 63.6% of CYP2C19*1/*1, 36.3% and 0% of CYP2C19*1/*2 and *2/*2 in the tolerance controls group, respectively. Conclusions: This is the first study to confirm the distribution of CYP2C19*2 allele and the prevalence of poor metabolizer genes in Thai patients who received medical cannabis for treatment. Thus, CYP2C19 allele might serve as a pharmacogenetics marker for screening before initiating treatment.

Keywords: medical cannabis, adverse drug reactions, CYP2C19, tetrahydrocannabinol, poor metabolizer

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Authors: Masuma Novak, Daniel Novak

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Background: Sweden along with other Nordic countries has the highest incidence of type 1 diabetes mellitus (T1DM) worldwide. The trend is increasing globally. The diagnosis is often given at the emergency clinic when children arrive with cardinal symptom of T1DM. Children with T1DM are known to have an increased risk of microvascular- and macrovascular complications. A family history of cardiovascular complications may further increase their risk. Clinically evident diabetes-related vascular complications are however rarely visible in childhood and adolescence, whereby an intensive diabetes treatment and normoglycemic control is a goal for every child. This study is a risk evaluation of children with T1DM based on their family’s cardiovascular history. Method: Since 2005 the Better Diabetes Diagnosis (BDD) study is a nationwide Swedish prospective cohort study that recruits new-onset T1DM who are less than 18 years old at time of diagnosis. For each newly diagnosed child, blood samples are collected for specific HLA genotyping and islet autoantibody assays and their family’s cardiovascular history is evaluated. As part of the BDD study, during the years 2010-2013 all children diagnosed with T1DM at the Queen Silvia’s Children’s Hospital in Sweden were asked about their family’s cardiovascular history. Questions regarded maternal and paternal high blood pressure, stroke, and myocardial infarction before the age of 55 years, and hyperlipidemia were answered. A maximum risk score of eight was possible. All children are clinically observed prospectively for early functional and structural abnormalities such as protein uremia, blood pressure, and retinopathy. Results: A total of 275 children aged 0 to 18 years were diagnosed with T1DM at the Queen Silvia’s Children’s Hospital emergency clinic during this four year period. The participation rate was 99.7%. 26.4% of the children had no hereditary cardiovascular risk factors. 22.7 % had one risk factor and 18.8% had two risk factors. 14.8% had three risk factors. 9.7% had four risk factors and 7.5% had five risk factors or more. Conclusion: Among children with T1DM in Sweden there is a difference in hereditary cardiovascular risk factors. These results indicate that children with T1DM who also have increased hereditary cardiovascular risk factors should be monitored closely with early screening for functional and structural cardiovascular abnormalities. This is a very preliminary and ongoing study which will be complemented with the cardiovascular risk analysis among children without T1DM.

Keywords: children, type I diabetes, emergency clinic, CVD risk

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Authors: Natalia Moreno-Castellanos, Amaia Rodriguez, Gema Frühbeck

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Introduction: In adipocytes, the cytoskeleton undergoes important expression and distribution in adipocytes rearrangements during adipogenesis and in obesity. Indeed, a role for these proteins in the regulation of adipocyte differentiation and response to insulin has been demonstrated. Recently, septins have been considered as new components of the cytoskeletal network that interact with other cytoskeletal elements (actin and tubulin) profoundly modifying their dynamics. However, these proteins have not been characterized as yet in adipose tissue. In this work, were examined the cellular, molecular and functional features of a member of this family, septin 11 (SEPT11), in adipocytes and evaluated the impact of obesity on the expression of this protein in human adipose tissue. Methods: Adipose gene and protein expression levels of SEPT11 were analysed in human samples. SEPT11 distribution was evaluated by immunocytochemistry, electronic microscopy, and subcellular fractionation techniques. GST-pull down, immunoprecipitation and a Yeast-Two Hybrid (Y2H) screening were used to identify the SEPT11 interactome. Gene silencing was employed to assess the role of SEPT11 in the regulation of insulin signaling and lipid metabolism in adipocytes. Results: SEPT11 is expressed in human adipocytes, and its levels increased in both omental and subcutaneous adipose tissue in obesity, with SEPT11 mRNA content positively correlating with parameters of insulin resistance in subcutaneous fat. In non-stimulated adipocytes, SEPT11 immunoreactivity showed a ring-like distribution at the cell surface and associated to caveolae. Biochemical analyses showed that SEPT11 interacted with the main component of caveolae, caveolin-1 (CAV1) as well as with the fatty acid-binding protein, FABP5. Notably, the three proteins redistributed and co-localized at the surface of lipid droplets upon exposure of adipocytes to oleate. In this line, SEPT11 silencing in 3T3-L1 adipocytes impaired insulin signaling and decreased insulin-induced lipogenesis. Conclusions: Those findings demonstrate that SEPT11 is a novel component of the adipocyte cytoskeleton that plays an important role in the regulation of lipid traffic, metabolism and can thus represent a potential biomarker of insulin resistance in obesity in adipocytes through its interaction with both CAV1 and FABP5.

Keywords: caveolae, lipid metabolism, obesity, septins

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Authors: Samira Mehrabi

Abstract:

Geriatric depression is a common late-life mental health disorder that increases morbidity and mortality. It has been shown that exercise is effective in alleviating symptoms of geriatric depression. However, inconsistencies across studies and lack of optimal dose-response of exercise for improving geriatric depression have made it challenging to draw solid conclusions on the effectiveness of exercise in late-life depression. Purpose: To further investigate the moderators of the effectiveness of exercise on geriatric depression across the current body of evidence. Methods: Based on the Arksey and O’Malley framework, an extensive search strategy was performed by exploring PubMed, Scopus, Sport Discus, PsycInfo, ERIC, and IBSS without limitations in the time frame. Eight systematic reviews with empirical results that evaluated the effect of exercise on depression among people aged ≥ 60 years were identified and their individual studies were screened for inclusion. One additional study was found through the hand searching of reference lists. After full-text screening and applying inclusion and exclusion criteria, 21 studies were retained for inclusion. Results: The review revealed high variability in characteristics of the exercise interventions and outcome measures. Sample characteristics, nature of comparators, main outcome assessment, and baseline severity of depression also varied notably. Mind-body and aerobic exercises were found to significantly reduce geriatric depression. However, results on the relationship between resistance training and improvements in geriatric depression were inconsistent, and results of the intensity-related antidepressant effects of exercise interventions were mixed. Extensive use of self-reported questionnaires for the main outcome assessment and lack of evidence on the relationship between depression severity and observed effects were of the other important highlights of the review. Conclusion: Several literature gaps were found regarding the potential effect modifiers of exercise and geriatric depression. While acknowledging the complexity of establishing recommendations on the exercise variables and geriatric depression, future studies are required to understand the interplay and threshold effect of exercise for treating geriatric depression.

Keywords: exercise, geriatric depression, healthy aging, older adults, physical activity intervention, scoping review

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