Search results for: cancer cell drug efficacy

Authors: Rishabh Hans, Saksham Sharma

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Drying of a sessile droplet imbibed with colloidal solution is a complex process in many aspects. Till now, most of the work revolves around; conditions for buckling onset, post-buckling effects, nature of change of droplet shape etc. In this work, we are determining the shape of daughter cavity (DC) formed during post-buckling onset, a less explored stage, and its relationship with experimental parameters. We have introduced solid angle as a special parameter that can quantify the shape of DC at any instant. It facilitates us to compare the shape while experimenting across different substrate types, droplet sizes and particle concentration. Furthermore, the angular location of ‘weak spot’ on the periphery of droplet, which marks the initiation of cavity growth, varies in different conditions. To solve this problem, we have evaluated the deflection angle of weak spots w.r.t. the vertical axis going through the middle of droplet. Subsequently, the solid angle subtended by DC is analyzed about that inclined axis. Finally, results of analysis allude that increasing colloidal concentration has inverse effect on the growth rate of cavity’s shape. Moreover, the cap radius of DC is observed lower for high PLR which makes the capillary pressure higher and thus tougher to expedite cavity formation relatively. This analysis can be helpful in further studies to relate the shape, deflection angle, growth rate of daughter cavity to the type of droplet crust formed in the end. Examining DC stage shall add another layer to nano-colloidal research which aims to influence many industrial applications like patterning, coatings, drug delivery, food processing etc.

Keywords: buckling of sessile droplets, daughter cavity, droplet evaporation, nanoporous shell formation, solid angle

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Authors: Hien Thi Dieu Truong, Mahmoud Al-Sarayreh, Pullanagari Reddy, Marlon M. Reis, Richard Archer

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New Zealand mānuka honey is a honeybee product derived mainly from Leptospermum scoparium nectar. The potent antibacterial activity of mānuka honey derives principally from methylglyoxal (MGO), in addition to the hydrogen peroxide and other lesser activities present in all honey. MGO is formed from dihydroxyacetone (DHA) unique to L. scoparium nectar. Mānuka honey also has an idiosyncratic phenolic profile that is useful as a chemical maker. Authentic mānuka honey is highly valuable, but almost all honey is formed from natural mixtures of nectars harvested by a hive over a time period. Once diluted by other nectars, mānuka honey irrevocably loses value. We aimed to apply hyperspectral imaging to honey frames before bulk extraction to minimise the dilution of genuine mānuka by other honey and ensure authenticity at the source. This technology is non-destructive and suitable for an industrial setting. Chemometrics using linear Partial Least Squares (PLS) and Support Vector Machine (SVM) showed limited efficacy in interpreting chemical footprints due to large non-linear relationships between predictor and predictand in a large sample set, likely due to honey quality variability across geographic regions. Therefore, an advanced modelling approach, one-dimensional convolutional neural networks (1D-CNN), was investigated for analysing hyperspectral data for extraction of biochemical information from honey. The 1D-CNN model showed superior prediction of honey quality (R² = 0.73, RMSE = 2.346, RPD= 2.56) to PLS (R² = 0.66, RMSE = 2.607, RPD= 1.91) and SVM (R² = 0.67, RMSE = 2.559, RPD=1.98). Classification of mono-floral manuka honey from multi-floral and non-manuka honey exceeded 90% accuracy for all models tried. Overall, this study reveals the potential of HSI and deep learning modelling for automating the evaluation of honey quality in frames.

Keywords: mānuka honey, quality, purity, potency, deep learning, 1D-CNN, chemometrics

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Authors: Farah Ali, Tehreem Fayyaz, Musadiq Idris

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The present work was undertaken to investigate effects of various extracts of withania somnifera for anti-diabetic activity in alloxan induced diabetic rabbits. Rabbits were acclimatized for a week to standard laboratory temperature. Animals were fed according to a strict schedule (8 am, 3 pm and 10 pm) with green fodder (Medicago sativa) and tap water ad libitum. Animals were divided into nine groups of six rabbits each in a random manner. Body weights and physical activities of all rabbits were recorded before start of experiments. The animals of group 1 and 2 were given lactose (250 mg/kg, p.o) and Withania somniferaroot powder (100 mg/kg, p.o) respectively daily from day 1-20. Animals of group 3 were given alloxan (100 mg/kg, i.v) as a single dose on day 1. Powdered root of Withania somnifera in the doses of 100, 150, 200 mg/kg and its aqueous and ethanol extracts (equivalent to 200 mg/kg of crude drug) were given to the treated animals (groups 4-8), respectively by oral route for three weeks (day 1-20o.d), along with alloxan (100 mg/kg, i.v) as a single dose on day 1. Group 9 was treated with metformin (200 mg/kg, p.o) daily from day 1-20, along with a single dose of alloxan (100 mg/ kg, i.v) on day 1. Fasting serum glucose concentration in groups 3-9 was increased significantly (p<0.05) on day 3, with a maximum increase (215.3 mg/dl) in animals of toxic control (TC) group (3) on day 21 of the experiment as compared to normal control (NC) group (1). Effects of different doses (100, 150, 200 mg/kg, p.o) of W. somnifera root powder (WS) decreased the fasting serum glucose concentration as compared to toxic control group, with a maximum decrease (88.3 mg/dl) in group 2 (treated control) on day 21 of the experiment. Metformin (200 mg/kg, p.o) (reference control), aqueous extract (AWS) and ethanol extract (EWS) of W. somnifera (equivalent to 100 mg/kg W.somnifera root, p.o) antagonized the effects of alloxan as compared to toxic control group. These results indicate that the W. somnifera possess significant anti–diabetic activity.

Keywords: diabetes, serum, glucose, blood, sugar, rabbits

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Authors: Velly Anatasia

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In the last few decades extensive research has been conducted into information technology (IT) adoption, testing a series of factors considered to be essential for improved diffusion. Some studies analyze IT characteristics such as usefulness, ease of use and/or security, others focus on the emotions and experiences of users and a third group attempts to determine the importance of socioeconomic user characteristics such as gender, educational level and income. The situation is similar regarding e-commerce, where the majority of studies have taken for granted the importance of including these variables when studying e-commerce adoption, as these were believed to explain or forecast who buys or who will buy on the internet. Nowadays, the internet has become a marketplace suitable for all ages and incomes and both genders and thus the prejudices linked to the advisability of selling certain products should be revised. The objective of this study is to test whether the socioeconomic characteristics of experienced e-shoppers such as gender rally moderate the effect of their perceptions of online shopping behavior. Current development of the online environment and the experience acquired by individuals from previous e-purchases can attenuate or even nullify the effect of these characteristics. The individuals analyzed are experienced e-shoppers i.e. individuals who often make purchases on the internet. The Technology Acceptance Model (TAM) was broadened to include previous use of the internet and perceived self-efficacy. The perceptions and behavior of e-shoppers are based on their own experiences. The information obtained will be tested using questionnaires which were distributed and self-administered to respondent accustomed using internet. The causal model is estimated using structural equation modeling techniques (SEM), followed by tests of the moderating effect of socioeconomic variables on perceptions and online shopping behavior. The expected findings of this study indicated that gender moderate neither the influence of previous use of the internet nor the perceptions of e-commerce. In short, they do not condition the behavior of the experienced e-shopper.

Keywords: Internet shopping, age groups, gender, income, electronic commerce

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Authors: B. J. Mahen, N. E. Lloyd-Gale, S. Johnson, W. P. Rakowicz, M. J. Harris, A. D. Miller

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Background: Migraine is a leading cause of disability in the world. Calcitonin gene-related peptide (CGRP) receptor antagonists offer an approach to migraine prophylaxis by inhibiting the inflammatory and vasodilatory effects of CGRP. In recent years, NICE licensed the use of three CGRP-receptor antagonists: Fremanezumab, Galcanezumab, and Erenumab. Here, we present the outcomes of CGRP-antagonist treatment in a cohort of patients who suffer from episodic or chronic migraine and have failed at least three oral prophylactic therapies. Methods: We offered CGRP antagonists to 86 patients who met the NICE criteria to start therapy. We recorded the number of headache days per month (HDPM) at 0 weeks, 3 months, and 12 months. Of those, 26 patients were switched to an alternative treatment due to poor response or side effects. Of the 112 total cases, 9 cases did not sufficiently maintain their headache diary, and 5 cases were not followed up at 3 months. We have therefore included 98 sets of data in our analysis. Results: Fremanezumab achieved a reduction in HDPM by 51.7% at 3 months (p<0.0001), with 63.7% of patients meeting NICE criteria to continue therapy. Patients trialed on Galcanezumab attained a reduction in HDPM by 47.0% (p=0.0019), with 51.6% of patients meeting NICE criteria to continue therapy. Erenumab, however, only achieved a reduction in HDPM by 17.0% (p=0.29), and this was not statistically significant. Furthermore, 34.4%, 9.7%, and 4.9% of patients taking Fremanezumab, Galcanezumab, and Erenumab, respectively, continued therapy beyond 12 months. Of those who attempted drug holidays following 12 months of treatment, migraine symptoms relapsed in 100% of cases. Conclusion: We observed a significant improvement in HDPM amongst episodic and chronic migraine patients following treatment with Fremanezumab or Galcanezumab.

Keywords: migraine, CGRP, fremanezumab, galcanezumab, erenumab

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Authors: Avirup Chowdhury, Angus K. McFadyen, Linsey Batchelor

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Blood cultures (BCs) are an important aspect of management of the septic patient, identifying the underlying pathogen and its antibiotic sensitivities. However, while the current literature outlines indications for initial BCs to be taken, there is little guidance for repeat sampling in the following 5-day period and little information on how antibiotic use can affect the usefulness of this investigation. A retrospective cohort study was conducted using inpatients who had undergone 2 or more BCs within 5 days between April 2016 and April 2017 at a 400-bed hospital in the west of Scotland and received antibiotic therapy between the first and second BCs. The data for BC sampling was collected from the electronic microbiology database, and cross-referenced with data from the hospital electronic prescribing system. Overall, 283 BCs were included in the study, taken from 92 patients (mean 3.08 cultures per patient, range 2-10). All 92 patients had initial BCs, of which 83 were positive (90%). 65 had a further sample within 24 hours of commencement of antibiotics, with 35 positive (54%). 23 had samples within 24-48 hours, with 4 (17%) positive; 12 patients had sampling at 48-72 hours, 12 at 72-96 hours, and 10 at 96-120 hours, with none positive. McNemar’s Exact Test was used to calculate statistical significance for patients who received blood cultures in multiple time blocks (Initial, < 24h, 24-120h, > 120h). For initial vs. < 24h-post BCs (53 patients tested), the proportion of positives fell from 46/53 to 29/53 (one-tailed P=0.002, OR 3.43, 95% CI 1.48-7.96). For initial vs 24-120h (n=42), the proportions were 38/42 and 4/42 respectively (P < 0.001, OR 35.0, 95% CI 4.79-255.48). For initial vs > 120h (n=36), these were 33/36 and 2/36 (P < 0.001,OR ∞). These were also calculated for a positive in initial or < 24h vs. 24-120h (n=42), with proportions of 41/42 and 4/42 (P < 0.001, OR 38.0, 95% CI 5.22-276.78); and for initial or < 24h vs > 120h (n=36), with proportions of 35/36 and 2/36 respectively (P < 0.001, OR ∞). This data appears to show that taking an initial BC followed by a BC within 24 hours of antibiotic commencement would maximise blood culture yield while minimising the risk of false negative results. This could potentially remove the need for as many as 46% of BC samples without adversely affecting patient care. BC yield decreases sharply after 48 hours of antibiotic use, and may not provide any clinically useful information after this time. Further multi-centre studies would validate these findings, and provide a foundation for future health policy generation.

Keywords: antibiotics, blood culture, efficacy, inpatient

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Authors: Fasil Wagnew, Kerri Viney, Kefyalew Addis Alene, Matthew Kelly, Darren Gray

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Background: Undernutrition is a risk factor for tuberculosis (TB), including poor treatment outcomes. However, evidence regarding the effect of undernutrition on TB treatment outcomes is not well understood. We aimed to evaluate the effect of undernutrition on sputum culture conversion and treatment outcomes among people with multi-drug resistance (MDR)-TB. Methods: We searched for publications in the Medline, Embase, Scopus, and Web of Science databases without restrictions on geography or year of publication. We conducted a random-effect meta-analysis to estimate the effects of undernutrition on sputum culture conversion and treatment outcomes. Two reviewers independently assessed the study eligibility, extracted the necessary information, and assessed the risk of bias. Depending on the nature of the data, odds ratio (OR) and hazard ratio (HR) with 95% confidence intervals (CIs) were used to summarize the effect estimates. Potential publication bias was checked using funnel plots and Egger’s tests. Results: Of 2358 records screened, 59 studies comprising a total of 31,254 people with MDR-TB were included. Undernutrition was significantly associated with a lower sputum culture conversion rate (HR 0·7, 95% CI 0·6–0·9, I2=67·1%) and a higher rate of mortality (OR 2·9, 95%CI 2·1–3·8, I2=23·7%) and unfavourable treatment outcomes (OR 1·8, 95%CI 1·5–2·0, I2=72·7%). There was no statistically significant publication bias in the included studies. Three studies were low, forty-two studies were moderate, and fourteen studies were high quality. Interpretations: Undernutrition was significantly associated with unfavourable treatment outcomes, including mortality and lower sputum culture conversion among people with MDR-TB. These findings have implications for supporting targeted nutritional interventions alongside standardised second-line TB drugs.

Keywords: undernutrition, MDR-TB, sputum culture conversion, treatment outcomes, meta-analysis

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Authors: Mohammad K. Rumjaun, Sana Amjed, Muhammad A. Ghazi, Safa G. Attar, Jason Raw

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Background: National Health Service (NHS) in England is one of the leading healthcare systems in the world and it heavily relies on the recruitment of overseas doctors. 30.7% of the doctors currently serving in NHS are overseas doctors. Most of these doctors do not receive the essential induction required to work in the NHS when they first arrive and therefore, they mostly struggle to work effectively in the first few months of their new jobs as compared to UK graduates. In our hospital, the clinical need for a dedicated induction programme for the International Medical Graduates (IMGs) was identified for their initial settling period and this programme was designed to achieve this. Methods: A questionnaire was designed for the previous 7 IMGs (Group 1) in order to identify the difficulties they faced in their initial phase. Thereafter, an induction programme consisting of presentations explaining the NHS and hospital framework, communication skills practice sessions, the clinical ceiling of care and patient simulation training was implemented for 6 new IMGs (Group 2). Another survey was done and compared with the previous. Results: After this programme, group 2 required only 1 week to understand the complexity of the IT systems as compared 3 weeks in group 1. 83% of group 2 was well-supported for their on-call duties after this programme as compared to 29% and 100% of group 2 was aware of their role in the job after the induction as compared to 0%. Furthermore, group 2 was able to function independently and confidently in their roles after only 1 month as compared to an average of 3 months for group 1. After running the PDSA cycles, our results show clear evidence that this programme has tremendously benefitted the IMGs in settling in the NHS. The IMGs really appreciated this initiative and have given positive feedback. Conclusion: Leaving your home country to begin your career in a different country is not an easy transition and undoubtedly, everyone struggles. It is important to invest in a well-structured induction programme for the IMGs in the initial phase of their jobs as this will improve not only their confidence and efficacy but also patients’ safety.

Keywords: induction programme, international medical graduates, NHS, overseas doctors struggles.

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Authors: Maged Syed Ahamd, Manal Mohamed Yasser, Essam Sholkamy

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In this paper, we reported that selenium (Se) nanoparticles were firstly biosynthesized with a simple and eco-friendly biological method. Their shape, size, FTIR (Fourier Transform Infrared spectroscopy), UV–vis spectra, TEM (Transmission Electron Microscopy) images and EDS (Energy Dispersive Spectroscopy) pattern have been analyzed. TEM analyses of the samples obtained at different stages indicated that the formation of these Se nanostructures was governed by an incubation time (12- 24- 48 hours). The Se nanoparticles were initially generated and then would transform into crystal seeds for the subsequent growth of nanowires; however obtaining stable Se nanowire with a diameter of about 15-100 nm. EDS shows that Se nanoparticles are entirely pure. The IR spectra showed the peaks at 550 cm-1, 1635 cm-1, 1994 cm-1 and 3430 cm-1 correspond to the presence of Se-O bending and stretching vibrations. The concentrations of Se-NPs (0, 1, 2, 5 µg/ml) did not give significantly effect on both two cell lines while the highest concentrations (10- 100 µg/ml gave significantly effects on them. The lethal dose (ID50%) of Se-NPs on Hep2 G and MCF-7 cells was obtained at 75.96 and 61.86 µg/ml, respectively. Results showed that Se nanoparticles as anticancer agent against MCF-7 cells were more effective than Hep2 G cells. Our results suggest that Se-NPs may be a candidate for further evaluation as a chemotherapeutic agent for breast and liver cancers.

Keywords: selenium nanoparticle, Streptomyces bikiniensis, nanowires, chemotherapeutic agent

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Authors: Levi Corallo

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Typed language made by humans on computers and cell phones has made a significant distinction from previous modes of written language exchanges. While acronyms remain one of the most predominant markings of typed language, another and perhaps more recent revolution in the way humans communicate has been with the use of symbols or glyphs, primarily Emojis—globally introduced on the iPhone keyboard by Apple in 2008. This paper seeks to analyze the use of symbols in typed communication from both a linguistic and machine learning perspective. The Unicode system will be explored and methods of encoding will be juxtaposed with the current machine and human perception. Topics in how typed symbol usage exists in conversation will be explored as well as topics across current research methods dealing with Emojis like sentiment analysis, predictive text models, and so on. This study proposes that sequential analysis is a significant feature for analyzing unicode characters in a corpus with machine learning. Current models that are trying to learn or translate the meaning of Emojis should be starting to learn using bi- and tri-grams of Emoji, as well as observing the relationship between combinations of different Emoji in tandem. The sociolinguistics of an entire new vernacular of language referred to here as ‘typed language’ will also be delineated across my analysis with unicode glyphs from both a semantic and technical perspective.

Keywords: unicode, text symbols, emojis, glyphs, communication

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Authors: Rama Bhargava, Surabhi Nishad

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The infusion of nanofluids has dramatically enhanced the heat-carrying capacity of the fluids, applicable to many engineering and medical process where the temperature below freezing is required. Cryosurgery is an efficient therapy for the treatment of cancer, but sometimes the excessive cooling may harm the nearby healthy cells. Efforts are therefore done to develop a model which can cause to generate the low temperature as required. In the present study, a mathematical model is developed based on the bioheat transfer equation to simulate the heat transfer from the probe on a tumor (with irregular domain) using the hybrid technique consisting of element free Galerkin method with αα-family of approximation. The probe is loaded will nano-particles. The effects of different nanoparticles, namely Al₂O₃, Fe₃O₄, Au on the heat-producing rate, is obtained. It is observed that the temperature can be brought to (60°C)-(-30°C) at a faster freezing rate on the infusion of different nanoparticles. Besides increasing the freezing rate, the volume of the nanoparticle can also control the size and growth of ice crystals formed during the freezing process. The study is also made to find the time required to achieve the desired temperature. The problem is further extended for multi tumors of different shapes and sizes. The irregular shape of the frozen domain and the direction of ice growth are very sensitive issues, posing a challenge for simulation. The Meshfree method has been one of the accurate methods in such problems as a domain is naturally irregular. The discretization is done using the nodes only. MLS approximation is taken in order to generate the shape functions. Sufficiently accurate results are obtained.

Keywords: cryosurgery, EFGM, hybrid, nanoparticles

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Authors: Amir Reza Heydari, Yaser Jenab

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Coronary artery disease, a common cardiovascular disease, is attributed to the accumulation of cholesterol-based plaques in the coronary arteries, leading to atherosclerosis. This disease is associated with risk factors such as smoking, hypertension, diabetes, and elevated cholesterol levels, contributing to severe clinical consequences, including acute coronary syndromes and myocardial infarction. Treatment approaches such as from lifestyle interventions to surgical procedures like percutaneous coronary intervention and coronary artery bypass surgery. These interventions often employ stents, including bare-metal stents (BMS), drug-eluting stents (DES), and bioresorbable vascular scaffolds (BVS), each with its advantages and limitations. Computational tools have emerged as critical in optimizing stent designs and assessing their performance. The aim of this study is to provide an overview of the computational methods of studies based on the finite element (FE) method in the field of coronary stenting and discuss the potential for development and clinical application of stent devices. Additionally, the importance of assessing the ability of computational models is emphasized to represent real-world phenomena, supported by recent guidelines from the American Society of Mechanical Engineers (ASME). Validation processes proposed include comparing model performance with in vivo, ex-vivo, or in vitro data, alongside uncertainty quantification and sensitivity analysis. These methods can enhance the credibility and reliability of in silico simulations, ultimately aiding in the assessment of coronary stent designs in various clinical contexts.

Keywords: atherosclerosis, materials, restenosis, review, validation

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Authors: Lubna Khondker

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Background: Melasma is a common pigmentary dermatosis, manifested by hyperpigmented macules or patches on the face, commonly occurring in females due to an acquired disorder in the melanogenesis process. Although several treatments are currently used, it remains a great challenge due to recurrence and refractory nature. It was recently reported that tranexamic acid (TA-plasmin inhibitor) is an effective treatment for melasma. Objective: This study aims to compare the efficacy and side effects of intralesional injection of Tranexamic acid with oral Tranexamic acid in the treatment of melasma. Methods: A clinical trial was done in the Department of Dermatology and Venereology, Bangabandhu Sheikh Mujib Medical University, for a period of 4 years. A total of 100 patients with melasma who did not respond to topical therapy were included in the study as group A and group B. Group A Patients were administered intralesional injection (10 mg/ml) of Tranexamic acid( TA) weekly for 6 weeks, and group B patients were treated with oral tranexamic acid 250 mg 12 hourly for 12 weeks after taking informed consent. The severity and extent of pigmentation were assessed by the modified melasma area severity index (MASI). The response to treatment was assessed by MASI at 4 weeks, 8 weeks, and 12 weeks after stopping treatment. Results: The study showed the MASI scores at the baseline, 4 weeks, 8 weeks, and 12 weeks in group A were 18.23±1.22, 6.14±3.26, 3.21±2.14 and 2.11±2.01 respectively, and in group B, 17.87±1.12, 11.21±6.25, 6.57±4.26 and 6.41±4.17 respectively. The mean MASI significantly reduced in group A compared to group B in the 4th, 8th, and 12th weeks. The present study showed that among group A patients, 56% rated excellent (>75% reduction) in outcome, 32% good (50-75% reduction), 8% moderate (25-50% reduction) and only 4% (<25% reduction) was unsatisfactory and among group B patients, 14% rated excellent in outcome, 28% good, 36% moderate and 22% was unsatisfactory. Overall improvement in our study in group A was 96% and in group B 78%. Side effects were negligible, and all the patients tolerated the treatment well. Conclusion: Based on our results, intralesional Tranexamic acid (10 mg/ml) is more effective and safer than oral Tranexamic acid in the treatment of melasma.

Keywords: intralesional tranexamic acid, melasma, oral tranexamic acid, MASI score

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Authors: Alicia Greenbank, Efrat Bengio

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The aim of this research was to examine the efficacy of the first course in Israel, whose objective is to train student teachers in the special education department to work cooperatively with parents of children with special needs. Studies often highlight the importance of cooperation between teachers and parents of students with special needs. Israel’s Special Education Law defines parents as complete partners, and the Ministry of Education encourages and even requires that partnership be present. Yet this partnership is difficult to achieve many kindergarten teachers, and teachers have a lot of difficulties establishing and managing a pattern of cooperation with their students’ parents. Often we see different perspectives on the child's development and needs, distrust, lack of appreciation, and communication difficulties on both sides – parents & teachers. The course describes a method of instilling the need for cooperation at an early stage of teacher training-in the teacher training program. 22 students in the special education program for early childhood education in the fourth year of learning took part in the course. The fourth-year is the experiential training year and the first time that students have worked in a school. The course consisted of 14 sessions. Seven parents of students with different disabilities participated at 6 of the sessions. The changes in the students' attitudes towards partnership and their ability to manage this partnership were carried out by examining the reports written by the students before the meetings with the parents and the reflections they wrote after each meeting with the parents and at the end of the course. Three themes emerged from the narrative analysis, corresponding to the three preconditions for joint activities with parents — Approach, Attitude, Appropriate Atmosphere, according to the Four A’s Model. The findings showed that a course combining meetings with parents of children with special needs offers many benefits for teacher training. The course raised student awareness of the question partnership, changed students’ approaches and attitudes towards the parents, stressed the importance of partnership, and provided students with tools for working with parents through the school. Based on the findings of this study, courses in this format can be applied in order to cooperate between teachers and parents, for example, parents of gifted children with special needs.

Keywords: Partnership with parents in special education, parents of children with disabilities, parents of children with special needs, parents’ involvement in special education

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Authors: Narin Salehiyan

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The later sequencing of the complete genomes of Mycoplasma genitalium and M. pneumoniae has pulled in significant consideration to the atomic science of mycoplasmas, the littlest self-replicating living beings. It shows up that we are presently much closer to the objective of defining, in atomic terms, the complete apparatus of a self-replicating cell. Comparative genomics based on comparison of the genomic cosmetics of mycoplasmal genomes with those of other microbes, has opened better approaches of looking at the developmental history of the mycoplasmas. There's presently strong hereditary bolster for the speculation that mycoplasmas have advanced as a department of gram-positive microbes by a handle of reductive advancement. Amid this prepare, the mycoplasmas misplaced significant parcels of their ancestors’ chromosomes but held the qualities basic for life. In this way, the mycoplasmal genomes carry a tall rate of preserved qualities, incredibly encouraging quality comment. The critical genome compaction that happened in mycoplasmas was made conceivable by receiving a parasitic mode of life. The supply of supplements from their has clearly empowered mycoplasmas to lose, amid advancement, the qualities for numerous assimilative forms. Amid their advancement and adjustment to a parasitic mode of life, the mycoplasmas have created different hereditary frameworks giving a profoundly plastic set of variable surface proteins to avoid the have safe framework.

Keywords: mycoplasma, plasma, pathogen, genome

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Authors: Sauradipta Ganguly, Akhato Sumi, Sanjeet Kumar Hom, Ajan T. Lotha

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Populus deltoides is a hardwood used predominantly for the manufacturing of plywood, matchsticks, and paper in India and hence has a higher economical significance. Wood-decaying fungi cause serious damage to Populus deltoides products, as the wood itself is perishable and vulnerable to decaying agents, decreasing their aesthetical value which in return results in significant monetary loss for the wood industries concerned. The aim of the study was to determine the antifungal activity of Cedrus deodara oil against three primary wood-decaying fungi namely white-rot fungi (Trametes versicolor), brown-rot fungi (Oligoporus placentus) and soft-rot fungi (Xylaria acuminata) on Populus deltoides samples under optimum laboratory conditions. The susceptibility of Populus deltoides samples on the fungal attack and the ability of deodar oil to control colonization of the wood rotting fungi on the samples were assessed. Three concentrations of deodar oil were considered for the study as treating solutions, i.e., 4%, 5%, and 6%. The Populus deltoides samples were treated with treating solutions, and the ability of the same to prevent a fungal attack on the samples were assessed using accelerated test in the laboratory at Biochemical Oxygen Demand incubator at temperature (25 ± 2°C) and relative humidity 70 ± 4%. Efficacy test and statistical analysis of deodar oil against Trametes versicolor, Oligoporus placentus, and Xylariaacuminataon P. deltoides samples exhibited light, minor and negligible mycelia growth at 4 %, 5% and 6% concentrations of deodar oil, respectively. Whereas, moderate to heavy attack was observed on the surface of the control samples. Statistical analysis further established that the treatments were statistically significant and had significantly inhibited fungal growth of all the three fungus spp by almost 3 to 5 times.

Keywords: populus deltoides, Trametes versicolor, Oligoporus placentus, Xylaria acuminata, Deodar oil, treatment

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Authors: Hafida Merzouk

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Urinary tract infections are among the most serious public health issues in all age groups. Thus, the empirical therapy should based on local levels of resistance, as indicated in several studies from different countries, to effectively avoid the emergence of multidrug-resistant bacterial strains and recurrent infections. Numerous effective antibiotic treatments are available, but wouldbe ineffective for treating recurrent cystitis caused by a urinary tract infection, as well as the emergence of drug resistance. That iswhy the aim of this study was to highlight the antibacterial and the antioxidant activity of 11 medicinal plants used traditionally in Algeria against E. coli, the most responsible urinary tract infections. First, the extraction of total polyphenols with aqueous acetone showed variable yields. The highest yield was obtained by Asplenium trichomanes with 27%, followed by Petroselinum crispum and Ciannamomum cassia with an equal yield of 21%. Artemisia herba-alba gave the lowest yield (9%). The extracts of different plants showed variable contents of phenolic compounds. Reducing power and DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging activity revealed that most of the extracts studied had significant activity. The anti-free radical activity was very high in the extract of A splenium adiantum-nigrum compared with the other extracts studied, but Petroselinum crispum and Parietaria officinalis had the lowest reducing activity; Antibacterial activity was determined on E. coli strainsusing the diffusion, MICs (Minimum Inhibitory Concentrations) and MBCs (Minimum Bactericidal concentrations) methods. The strains tested were sensitive to most extracts studied, except Asplenium adiantum-nigrum extract, for which both strains showed resistance.

Keywords: E. coli, medicinal plants, phenolic compounds, urinary infections

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Authors: C. A. Ologunde

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Escherichia coli have been a major microorganisms associated with, and isolated from feacal samples either in adult or children all over the world. Strains of these organisms are resistant to cephalosporins and fluoroquinolone (FQ) antimicrobial agents among hospitalized patients and FQs are the most frequently prescribed antimicrobial class in hospitals, and the level of resistant of E. coli to these antimicrobial agents is a risk factor that should be assessed. Hence, this study was conducted to determine the prevalence and risk factors for colonization with fluoroquinolone (FQ)-resistant E. coli in hospitalized patients in Ado-Ekiti. Rectal swabs were obtained from patients in hospitals in the study area and FQ-resistant E. coli were isolated and identified by means of Nalidixic acid multi-disk and a 1-step screening procedure. Species identification and FQ resistance were confirmed by automated testing (Vitek, bioMerieux, USA). Individual colonies were subjected to pulse-field gel electrophoresis (PAGE) to determine macro-restriction polymorphism after digestion of chromosomal DNA. FQ-resistant E. coli was detected in the stool sample of 37(62%) hospitalized patient. With multivariable analyses, the use of FQ before hospitalization was the only independent risk factor for FQ-resistant E. coli carriage and was consistent for FQ exposures for the 3-12 months of study. Pulsed-field gel electrophoresis of FQ-resistant E. coli identified conal spread of 1(one) strain among 18 patients. Loss (9 patients) or acquisition (10 residents) of FQ-resistant E. coli was documented and was associated with de novo colonization with genetically distinct strains. It was concluded that FQ-resistant E. coli carriage was associated with clonal spread. The differential effects of individual fluoroquinolone on antimicrobial drug resistance are an important area for future study, as hospitals manipulate their formularies with regard to use of individual fluoroquinolone, often for economic reasons.

Keywords: E. coli, fluoroquinolone, risk factors, feacal carriage, hospitalized patients, Ado-Ekiti

Procedia PDF Downloads 247

Authors: Kathleen Moyer, Nora Ait Boucherbil, Murtaza Zohair, Janna Eaves-Rathert, Cary Pint

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This study demonstrates the significance of interface engineering in the field of structural energy by being the first case where the performance of the system with the structural battery is greater than the performance of the same system with a battery separate from the system. The benefits of improving the interface in the structural battery were tested by creating carbon fiber composite batteries (and independent graphite electrodes and lithium iron phosphate electrodes) with and without an improved interface. Mechanical data on the structural batteries were collected using tensile tests and electrochemical data was collected using scanning electron microscopy equipment. The full-cell lithium-ion structural batteries had capacity retention of over 80% exceeding 100 cycles with an average energy density of 52 W h kg−1 and a maximum energy density of 58 W h kg−1. Most scientific developments in the field of structural energy have been done with supercapacitors. Most scientific developments with structural batteries have been done where batteries are simply incorporated into the structural element. That method has limited advantages and can create mechanical disadvantages. This study aims to show that a large improvement in structure energy research can be made by improving the interface between the structural device and the battery.

Keywords: composite materials, electrochemical performance, mechanical properties, polymer interface, structural batteries

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Authors: Anjana R. Menon, Anjana Bhasi

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This paper deals with the numerical analysis of Prefabricated Horizontal Drain (PHD) induced consolidation of clayey deposits, using ABAQUS. PHDs are much like Prefabricated Vertical Drains (PVDs) installed in horizontal layers, used mainly for enhancing the consolidation of clayey fill embankments, and dredged mud deposits. The efficiency of the system depends mainly on the spacing and layout of the drain. Hence, two spacing related parameters are defined, namely WH (width to horizontal spacing ratio) and VH (vertical to horizontal spacing ratio), and the finite element models are developed based on plane strain unit cell conditions under various combinations of these parameters. The analysis results, in terms of degree of consolidation (U), are compared with the established theories. Based on the analysis, a set of equations are proposed to analyse the PHD induced consolidation. The proposed method is found to be reasonably accurate. Further, the effect of PHDs at different spacing ratios, in accelerating consolidation of a clayey embankment fill is analysed in terms of pore pressure dissipation rate, and settlement. The PHD is found to accelerate the rate of pore pressure dissipation by more than 50%, thus reducing the time for final settlement significantly.

Keywords: ABAQUS, consolidation, plane strain, prefabricated horizontal drain

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Authors: Asmaa M. Fahim

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In this elucidation, we synthesized different heterocyclic compounds attached to Benzene sulfonamide moiety via (E)-N-(4-(3-(4-bromophenyl)acryloyl)phenyl)-4-methyl benzene sulfonamide which is obtained from Nucleophilic substitution reaction between 4-methylbenzene sulfonyl chloride and 1-(4-aminophenyl)ethan-1-one in pyridine to get N-(4-acetyl phenyl)-4-methyl benzenesulfonamide which reacted 4-bromobenzal dehyde undergoes aldol condensation in NaOH to afford the corresponding chalchone 4. Moreover, the reactivity of chalchone 4 showed several active methylene derivatives utilized the pressurized microwave irradiation as a green energy resource. Chalcone 4 was allowed to react with ethyl cyanoacetate and acetylacetone, respectively, at 70 °C with pressure under microwave reaction condition to afford the 5-cyano-6-oxo-1,2,5,6-tetrahydropyridin-2-yl)-4-methylbenzenesulfonamide 6 and N-(4'-acetyl-4''-bromo-5'-oxo-2',3',4',5'-tetrahydro-[1,1':3',1''-terphenyl]-4-yl)-4-methylbenzenesulfonamide 8 derivatives. Moreover, the reactivity of this sulphonamide chalchone with NH2NH2 in EtOH and acetic acid, which gave 2,5-dihydro-1H-imidazol-4-yl)-4-methyl benzenesulfonamide, 1H-pyrazol-3-yl)-4-methyl and reactivity with NH2OH.HCl gave isoxazol-3-yl)-4-methylbenzenesulfonamide derivatives. The synthesized compounds were screened for their ADME properties and directed to antitumor activity on HepG2 hepatocellular carcinoma and MCF-7 breast cancer and exhibited excellent behavior against standard drugs; these results were confirmed through molecular simulations with different proteins. Additionally, the Density Functional Theory analysis of optimized structures investigated their physical descriptors, FMO, ESP and MEP, which correlated with biological evaluation.

Keywords: synthesis, green chemistry, antitumor activity, DFT study

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Authors: Alisa Kazarina, Guntis Gerhards, Elina Petersone-Gordina, Ilva Pole, Viktorija Igumnova, Janis Kimsis, Valentina Capligina, Renate Ranka

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Human body is inhabited by a vast number of microorganisms, collectively known as the human microbiome, and there is a tremendous interest in evolutionary changes in human microbial ecology, diversity and function. The field of paleomicrobiology, study of ancient human microbiome, is powered by modern techniques of Next Generation Sequencing (NGS), which allows extracting microbial genomic data directly from archaeological sample of interest. One of the major techniques is 16S rRNA gene sequencing, by which certain 16S rRNA gene hypervariable regions are being amplified and sequenced. However, some limitations of this method exist including the taxonomic precision and efficacy of different regions used. The aim of this study was to evaluate the phylogenetic sensitivity of different 16S rRNA gene hypervariable regions for microbiome studies in the archaeological samples. Towards this aim, archaeological bone samples and corresponding soil samples from each burial environment were collected in Medieval cemeteries in Latvia. The Ion 16S™ Metagenomics Kit targeting different 16S rRNA gene hypervariable regions was used for library construction (Ion Torrent technologies). Sequenced data were analysed by using appropriate bioinformatic techniques; alignment and taxonomic representation was done using Mothur program. Sequences of most abundant genus were further aligned to E. coli 16S rRNA gene reference sequence using MEGA7 in order to identify the hypervariable region of the segment of interest. Our results showed that different hypervariable regions had different discriminatory power depending on the groups of microbes, as well as the nature of samples. On the basis of our results, we suggest that wider range of primers used can provide more accurate recapitulation of microbial communities in archaeological samples. Acknowledgements. This work was supported by the ERAF grant Nr. 1.1.1.1/16/A/101.

Keywords: 16S rRNA gene, ancient human microbiome, archaeology, bioinformatics, genomics, microbiome, molecular biology, next-generation sequencing

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Authors: Babak Nemat

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Background and Purpose: Non-alcoholic fatty liver is one of the most common liver disorders, which, as the most important cause of death from liver disease, has unpleasant consequences and complications. The aim of this study was to investigate the effect of an educational intervention based on a health belief model to prevent non-alcoholic fatty liver among women. Materials and Methods: This experimental study was performed among 110 women referring to comprehensive health service centers in Malayer City, west of Iran, in 2023. Using the available sampling method, 110 participants were divided into experimental and control groups. The data collection tool included demographic characteristics and a questionnaire based on the health belief model. In the experimental group, three one-hour training sessions were conducted in the form of pamphlets, lectures, and group discussions. Data were analyzed using SPSS software version 21, by correlation tests, paired t-tests, and independent t-tests. Results: The mean age of participants was 38.07±6.28 years, and most of the participants were middle-aged, married, housewives with academic education, middle-income, and overweight. After the educational intervention, the mean scores of the constructs include perceived sensitivity (p=0.01), perceived severity (p=0.01), perceived benefits (p=0.01), guidance for internal (p=0.01), and external action (p=0.01), and perceived self-efficacy (p=0.01) in the experimental group were significantly higher than the control group. The score of perceived barriers in the experimental group decreased after training. The perceived obstacles score in the test group decreased after the training (15.2 ± 3.9 v.s 11.2 ± 3.3, (p<0.01). Conclusion: The findings of the study showed that the design and implementation of educational programs based on the constructs of the health belief model can be effective in preventing women from developing higher levels of non-alcoholic fatty liver.

Keywords: non-alcoholic fatty liver, health belief model, education, women

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Authors: Alok Madan, Arshad K. Hashmi

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The paper presents a plastic analysis procedure based on the energy balance concept for performance based seismic retrofit of multi-story multi-bay masonry infilled reinforced concrete (R/C) frames with a ‘soft’ ground story using passive energy dissipation (PED) devices with the objective of achieving a target performance level of the retrofitted R/C frame for a given seismic hazard level at the building site. The proposed energy based plastic analysis procedure was employed for developing performance based design (PBD) formulations for PED devices for a simulated application in seismic retrofit of existing frame structures designed in compliance with the prevalent standard codes of practice. The PBD formulations developed for PED devices were implemented for simulated seismic retrofit of a representative code-compliant masonry infilled R/C frame with a ‘soft’ ground story using friction dampers as the PED device. Non-linear dynamic analyses of the retrofitted masonry infilled R/C frames is performed to investigate the efficacy and accuracy of the proposed energy based plastic analysis procedure in achieving the target performance level under design level earthquakes. Results of non-linear dynamic analyses demonstrate that the maximum inter-story drifts in the masonry infilled R/C frames with a ‘soft’ ground story that is retrofitted with the friction dampers designed using the proposed PBD formulations are controlled within the target drifts under near-field as well far-field earthquakes.

Keywords: energy methods, masonry infilled frame, near-field earthquakes, seismic protection, supplemental damping devices

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Authors: Mohammad Jamal

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Non-alcoholic fatty liver disease (NAFLD) has become one of the most chronic liver diseases, prevalent among people with morbid obesity. NAFLD does not develop clinically significant liver disease, however cirrhosis and liver cancer develop in subset and currently there are no approved therapies for the treatment of NAFLD. The study is aimed to understand the various key genes involved in the mechanism of NAFLD which can be valuable for developing diagnostic and predictive biomarkers based on their histologic stage of liver. The study was conducted on 16 male Sprague Dawley rats. The animals were divided in two groups: control group (n=8) fed on ad libitum normal chow and regular water and the cafeteria group (CAF)) (n=8) fed on high fatty/ carbohydrate diet. The animals received their respective diet from 4 weeks onwards from D.O.B until 25 weeks. Liver was extracted and RT² Profiler PCR Array was used to assess the NAFLD related genes. Histological evaluation was performed using H&E stain in liver tissue sections. Our PCR array results showed that genes involved in anti-inflammatory activity (Ifng, IL10), fatty acid uptake/oxidation (Fabp5), apoptosis (Fas), lipogenesis (Gck and Srebf1), Insulin signalling (Igfbp1) and metabolic pathway (pdk4) were upregulated in the liver of cafeteria fed obese rats. Bloated hepatocytes, displaced nucleus and higher lipid content were seen in the liver of cafeteria fed obese rats. Although Liver biopsies remain the gold standard in evaluating NAFLD, however an approach towards non-invasive markers could be used in understanding the physiology, therapeutic potential, and the targets to combat NAFLD.

Keywords: biomarkers, cafeteria diet, obesity, NAFLD

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Authors: Fatma H. Galal, Alaaeddeen M. Seufi

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Due to the increasing usage of mobile phone, experiments were designed to investigate ‎the effect of acute dose exposure on the mosquito life cycle. 50 tubes (5 ml size) ‎containing 3 ml water and a first instar larva of the mosquito, Culex univittatus were put ‎between two mobile cell phones switched on talking mode for 4 continuous hours. A ‎control group of tubes (unexposed to radiation) were used. Larval and pupal durations ‎were calculated. Furthermore, adult emergence and sex ratio were observed for both ‎treated and control larvae. Results indicated that the employed dose of radiation reduced ‎total larval duration to about half the value of control. 1st, 2nd, 3rd and 4th larval ‎durations were reduced significantly by mobile radiation when compared to controls. ‎Meanwhile pupal duration was elongated significantly by mobile radiation when ‎compared to control. Sex ratio was significantly shifted in favor of females in the case of ‎radiated mosquitoes. Successful adult emergence was decreased significantly in the case ‎of radiated insects when compared to controls. Molecular studies to investigate the ‎effects of mobile radiation on insects and other model organisms are going on.‎

Keywords: mosquito, mobilr radiation, larval and pupal durations, sex ratio

Procedia PDF Downloads 185

Authors: Debajyoti Bose

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Chitosan has received much attention as a functional biopolymer for diverse applications, especially in pharmaceutics and medicine. Chitosan is a positively charged natural biodegradable and biocompatible polymer. It is a linear polysaccharide consisting of β-1,4 linked monomers of glucosamine and N-acetylglucosamine. Chitosan can be mainly obtained from fungal sources during large fermentation process. In this study,three different fungal strains Aspergillus niger NCIM 1045, Aspergillus oryzae NCIM 645 and Mucor indicus MTCC 3318 were used for the production of chitosan. The growth mediums were optimized for maximum fungal production. The produced chitosan was characterized by determining degree of deacetylation. Chitosan possesses one reactive amino at the C-2 position of the glucosamine residue, and these amines confer important functional properties to chitosan which can be exploited for biofabrication to generate various chemically modified derivatives and explore their potential for pharmaceutical field. Chitosan nanoparticles were prepared by ionic cross-linking with tripolyphosphate (TPP). The major effect on encapsulation and release of protein (e.g. enzyme diastase) in chitosan-TPP nanoparticles was investigated in order to control the loading and release efficiency. It was noted that the chitosan loading and releasing efficiency as a nanocapsule, obtained from different fungal sources was almost near to initial enzyme activity(12026 U/ml) with a negligible loss. This signify, chitosan can be used as a polymeric drug as well as active component or protein carrier material in dosage by design due to its appealing properties such as biocompatibility, biodegradability, low toxicity and relatively low production cost from abundant natural sources. Based upon these initial experiments, studies were also carried out on modification of chitosan based nanocapsules incorporated with physiologically important enzymes and nutraceuticals for target delivery.

Keywords: fungi, chitosan, enzyme, nanocapsule

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Authors: Azadeh Yasari, Michael Ganzle, Stephen Strelkov, Nuanyi Liang, Jonathan Curtis, Nat N. V. Kav

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Pathogenic fungi cause significant yield losses and quality reductions to major crops including wheat, canola, and barley. Toxic metabolites produced by phytopathogenic fungi also pose significant risks to animal and human health. Extensive application of synthetic fungicides is not a sustainable solution since it poses risks to human, animal and environmental health. Unsaturated fatty acids may provide an environmentally friendly alternative because of their direct antifungal activity against phytopathogens as well as through the stimulation of plant defense pathways. The present study assessed the in vitro and in vivo efficacy of two hydroxy fatty acids, coriolic acid and ricinoleic acid, against the phytopathogens Fusarium graminearum, Pyrenophora tritici-repentis, Pyrenophora teres f. teres, Sclerotinia sclerotiorum, and Leptosphaeria maculans. Antifungal activity of coriolic acid and ricinoleic acid was evaluated using broth micro-dilution method to determine the minimum inhibitory concentration (MIC). Results indicated that both ricinoleic acid and coriolic acid showed antifungal activity against phytopathogens, with the strongest inhibitory activity against L. maculans, but the MIC varied greatly between species. An antifungal effect was observed for coriolic acid in vivo against pathogenic fungi of wheat and barley. This effect was not correlated to the in vitro activity because ricinoleic acid with equivalent in vitro antifungal activity showed no protective effect in vivo. Moreover, neither coriolic acid nor ricinoleic acid controlled fungal pathogens of canola. In conclusion, coriolic acid inhibits some phytopathogens in vivo and may have the potential to be an effective crop protection agent.

Keywords: coriolic acid, minimum inhibitory concentration, pathogenic fungi, ricinoleic acid

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Authors: SeyedMohammad Hosseini, Amirhossein Moghanian

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The main purpose of this research was to design a biomimetic system by freeze-drying method for evaluating the effect of adding 5 and 10 mol. % of zinc (Zn)in 58S bioactive glass and gelatin (5ZnBG/G and 10ZnBG/G) in terms of structural and biological changes. The structural analyses of samples were performed by X-Ray Diffraction (XRD), scanning electron microscopy (SEM), and Fourier-transform infrared spectroscopy (FTIR). Also, 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide(MTT) and alkaline phosphate (ALP) activity test were carried out for investigation of MC3T3-E1cell behaviors. The SEM results demonstrated the spherical shape of the formed hydroxyapatite (HA) phases, and also HA characteristic peaks were detected by X-ray diffraction spectroscopy (XRD)after 3 days of immersion in the simulated body fluid (SBF) solution. Meanwhile, FTIR spectra proved that the intensity of P–O peaks for 5ZnBG/G was more than 10ZnBG/G and control samples. Moreover, the results of alkaline phosphatase activity (ALP) test illustrated that the optimal amount of Zn (5ZnBG/G) caused a considerable enhancement in bone cell growth. Taken together, the scaffold with 5 mol.% Zn was introduced as an optimal sample because of its higher biocompatibility, in vitro bioactivity, and growth of MC3T3-E1cellsin in comparison with other samples in bone tissue engineering.

Keywords: scaffold, gelatin, modified bioactive glass, alp, bone tissue engineering

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Authors: Ngawang Tsering

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Traditional Tibetan medicine is primarily focused on promoting health and keeping away diseases from its unique in prescribing specific diet and lifestyle. The prevalence of chronic diseases has been rising day by day and kills a number of people due to the lack of proper nutritional design in modern times. According to traditional Tibetan medicine, chronic diseases such as diabetes, cancer, cardiovascular diseases, respiratory diseases, and arthritis are heavily associated with an unwholesome diet and inappropriate lifestyles. Diet and lifestyles are the two main conditions of diseases and healthy life. The prevalence of chronic diseases is one of the challenges, with massive economic impact and expensive health issues. Though chronic diseases are challenges, it has a solution in the preventive measurements by using proper nutrition design based on traditional Tibetan medicine. Until today, it is hard to evaluate whether traditional Tibetan medicine nutrition strategy could play a major role in preventive measurement as of the lack of current research evidence. However, compared with modern nutrition, it has an exclusive valuable concept, such as a holistic way and diet or nutrition recommendation based on different aspects. Traditional Tibetan medicine is one of the oldest ancient existing medical systems known as Sowa Rigpa (Science of Healing) highlights different aspects of dietetics and nutrition, namely geographical, seasonal, age, personality, emotional, food combination, the process of individual metabolism, potency, and amount of food. This article offers a critical perspective on the preventive measurement against chronic diseases through nutrition design using traditional Tibetan medicine and also needs attention for a deeper understanding of traditional Tibetan medicine in the modern world.

Keywords: traditional Tibetan medicine, nutrition, chronic diseases, preventive measurement, holistic approach, integrative

Procedia PDF Downloads 158