Search results for: phytochemical Screening

Authors: A. N.Ukwuani, A. K. Abdulfatah

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G. crenata is used locally for the treatment of fractured bones, wound healing and inflammatory conditions. In vitro and in vivo antioxidant activity of hydromethanolic extracts of the leaves of G. crenata were assessed. The phytochemical analysis shows the presence of phenols, flavonoids, saponins, cardiac glycosides and tannins. An in vitro quantitative analysis of phenols, flavonoids and tannins respectively were (164±1.20, 199±0.88 and 88.67±0.88 mg/100g FW). In vivo studies of hydromethanolic extract demonstrated a dose dependent increase in hepatic superoxide dismutase (1.14±0.14, 2.13±0.11, 2.55±0.11 U/mg Protein) with improvement in hepatic glutathione (6.98±0.42, 8.91±0.37, 11.07±0.46 µM/mg Protein) and Catalase (4.47±0.05, 6.24±0.02, 7.17±0.04 U/mg Protein) and Total protein (6.18±0.08, 6.69±0.18, 7.27±0.16 mg/ml) respectively at 100-300mg/kg body weight Grewia crenata leaves when compared to the control and standard drug. It can be concluded from the present findings of that G. crenata leaves possess antioxidant potential.

Keywords: Grewia crenata, antioxidant, hydromethanolic extract, in vivo, in vitro

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Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi

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Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.

Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation

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Authors: R. Pravin Kumar, L. Roopa

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Enzymes are molecular machines used in various industries such as pharmaceuticals, cosmetics, food and animal feed, paper and leather processing, biofuel, and etc. Nevertheless, this has been possible only by the breath-taking efforts of the chemists and biologists to evolve/engineer these mysterious biomolecules to work the needful. Main agenda of this enzyme engineering project is to derive screening and selection tools to obtain focused libraries of enzyme variants with desired qualities. The methodologies for this research include the well-established directed evolution, rational redesign and relatively less established yet much faster and accurate insilico methods. This concept was initiated as a Receptor Rependent-4Dimensional Quantitative Structure Activity Relationship (RD-4D-QSAR) to predict kinetic properties of enzymes and extended here to study transaminase by a 7D QSAR approach. Induced-fit scenarios were explored using Quantum Mechanics/Molecular Mechanics (QM/MM) simulations which were then placed in a grid that stores interactions energies derived from QM parameters (QMgrid). In this study, the mutated enzymes were immersed completely inside the QMgrid and this was combined with solvation models to predict descriptors. After statistical screening of descriptors, QSAR models showed > 90% specificity and > 85% sensitivity towards the experimental activity. Mapping descriptors on the enzyme structure revealed hotspots important to enhance the enantioselectivity of the enzyme.

Keywords: QMgrid, QM/MM simulations, RD-4D-QSAR, transaminase

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Authors: Taha Anjamrooz, Sareh Rajabi, Salwa Bheiry

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Selection between the available projects in bidding processes for the contractor is one of the essential areas to concentrate on. It is important for the contractor to choose the right projects within its portfolio during the tendering stage based on certain criteria. It should align the bidding process with its origination strategies and goals as a screening process to have the right portfolio pool to start with. Secondly, it should set the proper framework and use a suitable technique in order to optimize its selection process for concertation purpose and higher efforts during the tender stage with goals of success and winning. In this research paper, a two steps framework proposed to increase the efficiency of the contractor’s bidding process and the winning chance of getting the new projects awarded. In this framework, initially, all the projects pass through the first stage screening process, in which the portfolio basket will be evaluated and adjusted in accordance with the organization strategies to the reduced version of the portfolio pool, which is in line with organization activities. In the second stage, the contractor uses linear programming to optimize the portfolio pool based on available resources such as manpower, light equipment, heavy equipment, financial capability, return on investment, and success rate of winning the bid. Therefore, this optimization model will assist the contractor in utilizing its internal resource to its maximum and increase its winning chance for the new project considering past experience with clients, built-relation between two parties, and complexity in the exertion of the projects. The objective of this research will be to increase the contractor's winning chance in the bidding process based on the success rate and expected return on investment.

Keywords: bidding process, internal resources, optimization, contracting portfolio management

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Authors: Haaris Khan, Farhad Udwadia

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South Asians are the fastest-growing immigrant population in Canada and are 3-4 times more likely to develop diabetes. In a primary care setting, language barriers continue to persist as a prominent obstacle when delivering crucial health information. Given the abundance of languages in the South Asian community and the varying levels of English fluency, there is compelling evidence that these language barriers can adversely impact health outcomes. The microvascular and macrovascular complications of poor diabetic management are well established and universally recognized. However, these are often difficult concepts to grasp for even individuals fluent in English. In order to lessen the burden of language barriers, we developed a comprehensive guide in various languages that discuss the complications and screening guidelines for diabetic and prediabetic patients. The guide is presented in the form of a pamphlet, with an electronic version being constructed as well, that provides basic information on diabetic retinopathy, neuropathy and nephropathy as well as the screening recommendations. We also conducted a review of the literature around the topic and incorporated our findings into our project. Our goal is for primary care physicians to have this resource and to be able to provide the link or pamphlet to patients in need. Our presentation also provides a comprehensive overview of some of the other barriers that individuals in the South Asian community face when seeking care. Given the staggering number of individuals in the South Asian community with diabetes and the morbidity and mortality associated with diabetes and its complications, effective community-specific strategies are needed to mitigate the potential consequences of poor diabetes management.

Keywords: diabetes, patient education, ophthalmology, vascular surgery

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Authors: P. G. S. Madushani, L. D. Illeperuma

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Abstract Noise is one of the most common physical hazards in industrial settings. The prevalence of Noise Induced Hearing Loss (NIHL) is on the rise with increasedduration of exposure and the increase in the severity of hearing loss. The purpose of the study was to determine auditory effects among textile workers and to establish associations between the degree of hearing loss and exposure duration, degree of hearing loss and noise level and the proportion of hearing related complaints. A cross sectional descriptive study using purposive sampling was carried out. An interviewer administered questionnaire and Distortion Product Oto Acoustic Emission (DPOAE) hearing screening on 127 (72 female and 55 male) textile workers of the selected textile plant in Seeduwa, Sri Lanka was done (Age: M= 31.16, SD=7.75). Noise measurements were done in six sections of the factory and average noise levels were obtained. Diagnostic hearing evaluations were done for 60 (57.75%) subjects, referred from the DPOAE hearing screening test. The degree of hearing loss and the exposure duration had a significant association in the high frequency region of 4 kHz to 8 kHz (p < 0.05). Noise levels fluctuated between 90.3±0.8 dBA and 50.6. ±0.52 dBA. 30.83% of workers reported having NIHL. Most of the workers (33.9%) complained difficulty in conversing in noisy backgrounds. Other complaints as tinnitus, dizziness, ear fullness and headache were reported in less than 30%. workers who were exposed to noise for more than 15 years were affected with NIHL in the high frequency region. Administrative controls and engineering controls need to be implemented to manage hazardous noise levels in industrial settings. Hearing Conservation Programs should be initiated and implemented for textile workers.

Keywords: textile industry, NIHL, degree of hearing loss, noise levels, auditory effects

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Authors: Ahmad Ali Shahid, M Shakil Shaukat

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Agriculture is the backbone of economy of Pakistan and Cotton is the major agricultural export and supreme source of raw fiber for our textile industry. To combat against the developing resistance in the target insects and combating these challenges wholesomely, a novel combination of pyramided/stacked genes was conceptualized and later realized, through the means of biotechnology i.e., transformation of three genes namely, Cry1Ac, Cry2A, and EPSP synthase (glyphosate tolerant) genes in the locally cultivated cotton variety. The progenies of the transformed plants were successfully raised and screened under the tunnel conditions for two generations and the present study focused on the screening of plants which were confirmed for containing all of these three genes and their expressions. Initially, the screening was done through glyphosate spray assay and the plants which were healthy and showed no damage on leaves were selected after 07 days of spray. In the laboratory, the DNA of these plants were isolated and subjected to amplification of the three genes. Thus, seventeen out of twenty were confirmed positive for Cry1Ac gene and ten out of twenty were positive for Cry2A gene and all twenty were positive for presence of EPSP synthase gene. Then, the ten plant samples which were confirmed with presence of all three genes were subjected to expression analysis of these proteins through ELISA. The results showed that eight out of ten plants were actively expressing the three transgenes. Real-time PCR was also done to quantify the expression levels of the EPSP synthase gene. Finally, eight plants were confirmed for the presence and active expression of all three genes in T3 generation of the triple gene transformed cotton. These plants may be subjected to T4 generation to develop a new stable variety in due course of time.

Keywords: agriculture, cotton, transformation, cry genes, ELISA, PCR

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Authors: Ahmad Jawad Fardin

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Over 60% of patients with breast cancer in Afghanistan present late with advanced stage III and IV, a major cause for the poor survival rate. The objectives of this study were to identify the contributing factors for the diagnosis and treatment delay and its outcome. This cross-sectional study was conducted on 318 patients with histologically confirmed breast cancer in the oncology department of Jamhoriat hospital, which is the first and only national cancer center in Afghanistan; data were collected from medical records and interviews conducted with women diagnosed with breast cancer, linear regression and logistic regression were used for analysis. Patient delay was defined as the time from first recognition of symptoms until first medical consultation and doctor form first consultation with a health care provider until histological confirmation of breast cancer. The mean age of patients was 49.2+_ 11.5years. The average time for the final diagnosis of breast cancer was 8.5 months; most patients had ductal carcinoma 260.7 (82%). Factors associated with delay were low education level 76% poor socioeconomic and cultural conditions 81% lack of cancer center 73% lack of screening 19%. The stage distribution was as follows stage IV 4 22% stage III 44.4% stage II 29.3% stage I 4.3%. Complex associated factors were identified to delayed the diagnosis of breast cancer and increased adverse outcomes consequently. Raising awareness and education in women, the establishment of cancer centers and providing accessible diagnosis service and screening, training of general practitioners; required to promote early detection, diagnosis and treatment.

Keywords: delayed diagnosis and poor outcome, breast cancer in Afghanistan, poor outcome of delayed breast cancer treatment, breast cancer delayed diagnosis and treatment in Afghanistan

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Authors: Cornelia-Eugenia Munteanu

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From a psychological perspective, psychopathology is the area of clinical psychology that has at its core psychological assessment and psychotherapy. In day-to-day clinical practice, psychodiagnosis and psychotherapy are used independently, according to their intended purpose and their specific methods of application. The paper explores how the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and Mini Mental State Examination-2 (MMSE-2) psychological tools contribute to enhancing the effectiveness of cognitive behavioral psychotherapy (CBT). This combined approach, psychotherapy in conjunction with assessment of personality and cognitive functions, is illustrated by two cases, a severe depressive episode with psychotic symptoms and a mixed anxiety-depressive disorder. The order in which CBT, MMPI-2, and MMSE-2 were used in the diagnostic and therapeutic process was determined by the particularities of each case. In the first case, the sequence started with psychotherapy, followed by the administration of blue form MMSE-2, MMPI-2, and red form MMSE-2. In the second case, the cognitive screening with blue form MMSE-2 led to a personality assessment using MMPI-2, followed by red form MMSE-2; reapplication of the MMPI-2 due to the invalidation of the first profile, and finally, psychotherapy. The MMPI-2 protocols gathered useful information that directed the steps of therapeutic intervention: a detailed symptom picture of potentially self-destructive thoughts and behaviors otherwise undetected during the interview. The memory loss and poor concentration were confirmed by MMSE-2 cognitive screening. This combined approach, psychotherapy with psychological assessment, aligns with the trend of adaptation of the psychological services to the everyday life of contemporary man and paves the way for deepening and developing the field.

Keywords: assessment, cognitive behavioral psychotherapy, MMPI-2, MMSE-2, psychopathology

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Authors: H. Aldewachi, M. Hines, M. McCulloch, N. Woodroofe, P. Gardiner

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DPP-IV is an enzyme whose expression is affected in a variety of diseases, therefore, has been identified as possible diagnostic or prognostic marker for various tumours, immunological, inflammatory, neuroendocrine, and viral diseases. Recently, DPP-IV enzyme has been identified as a novel target for type II diabetes treatment where the enzyme is involved. There is, therefore, a need to develop sensitive and specific methods that can be easily deployed for the screening of the enzyme either as a tool for drug screening or disease marker in biological samples. A variety of assays have been introduced for the determination of DPP-IV enzyme activity using chromogenic and fluorogenic substrates, nevertheless these assays either lack the required sensitivity especially in inhibited enzyme samples or displays low water solubility implying difficulty for use in vivo samples in addition to labour and time-consuming sample preparation. In this study, novel strategies based on exploiting the high extinction coefficient of gold nanoparticles (GNPs) are investigated in order to develop fast, specific and reliable enzymatic assay by investigating synthetic peptide sequences containing a DPP IV cleavage site and coupling them to GNPs. The DPP IV could be detected by colorimetric response of peptide capped GNPs (P-GNPS) that could be monitored by a UV-visible spectrophotometer or even naked eyes, and the detection limit could reach 0.01 unit/ml. The P-GNPs, when subjected to DPP IV, showed excellent selectivity compared to other proteins (thrombin and human serum albumin) , which led to prominent colour change. This provided a simple and effective colorimetric sensor for on-site and real-time detection of DPP IV.

Keywords: gold nanoparticles, synthetic peptides, colorimetric detection, DPP-IV enzyme

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Authors: S. Takaidza, M. Pillay, F. Mtunzi

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Since time immemorial, plants have been used by several communities to treat a large number of diseases. Numerous studies on the pharmacology of medicinal plants have been done. Medicinal plants constitute a potential source for the production of new medicines and may complement conventional antimicrobials and probably decrease health costs. Phytochemical compounds in plants are known to be biologically active aiding, for example, as antioxidants and antimicrobials. The overwhelming challenge of drug resistance has resulted in an increasing trend towards using medicinal plants to treat various diseases, especially in developing countries. Species of the genus Tulbaghia has been widely used in traditional medicine to treat various ailments such rheumatism, fits, fever, earache, tuberculosis etc. It is believed that the species possess several therapeutic properties. This paper evaluates some of the biological activities of the genus Tulbaghia. It is evident from current literature that T. violacea is the most promising species. The other species of Tulbaghia still require further studies to ascertain their medicinal potential.

Keywords: biological activities, antimicrobial, antioxidant, phytochemicals, tulbaghia

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Authors: Z. Razi, S. M. J. Mortazavi, N. Shokrpour, Z. Shayan, F. Amiri

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Long-term exposure to low doses of ionizing radiation occurs in radiation health care workplaces. Although doses in health professions are generally very low, there are still matters of concern. The radiation safety program promotes occupational radiation safety through accurate and reliable monitoring of radiation workers in order to effectively manage radiation protection. To achieve this goal, it has become mandatory to implement health examination periodically. As a result, based on the hematological alterations, working populations with a common occupational radiation history are screened. This paper calls into question the effectiveness of blood component analysis as a screening program which is mandatory for medical radiation workers in some countries. This study details the distribution and trends of changes in blood components, including white blood cells (WBCs), red blood cells (RBCs) and platelets as well as received cumulative doses from occupational radiation exposure. This study was conducted among 199 participants and 100 control subjects at the medical imaging departments at the central hospital of Shiraz University of Medical Sciences during the years 2006–2010. Descriptive and analytical statistics, considering the P-value<0.05 as statistically significance was used for data analysis. The results of this study show that there is no significant difference between the radiation workers and controls regarding WBCs and platelet count during 4 years. Also, we have found no statistically significant difference between the two groups with respect to RBCs. Besides, no statistically significant difference was observed with respect to RBCs with regards to gender, which has been analyzed separately because of the lower reference range for normal RBCs levels in women compared to men and. Moreover, the findings confirm that in a separate evaluation between WBCs count and the personnel’s working experience and their annual exposure dose, results showed no linear correlation between the three variables. Since the hematological findings were within the range of control levels, it can be concluded that the radiation dosage (which was not more than 7.58 mSv in this study) had been too small to stimulate any quantifiable change in medical radiation worker’s blood count. Thus, use of more accurate method for screening program based on the working profile of the radiation workers and their accumulated dose is suggested. In addition, complexity of radiation-induced functions and the influence of various factors on blood count alteration should be taken into account.

Keywords: blood cell count, mandatory testing, occupational exposure, radiation

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Authors: Nadiya Zahra Karimi, Amir Ghiami Rad

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The physical health of students from an early age and the proper formation of the musculoskeletal system of their body is part of the overall health of these people. Most chronic musculoskeletal problems and pains can be controlled and reduced with education at an early age. Therefore, with the correct and timely diagnosis of these abnormalities, we can play an important role in their proper treatment and control, and in a way, raise the level of quality of life and positive self-concept in students. The aim of this study was to investigate the relationship between erectile dysfunctions of the upper limbs (head and neck, shoulder, thoracic and lumbar) and the quality of life and self-concept of male students aged 7 to 10 years. The statical population of the study consists of 227 students of shahadat boys’ primary school in khajeh city. Due to the corona pandemic conditions, the research samples were identified after screening and available according to the entrance criteria of the study. To validate the quality of life, the valid WHOQOL-BREF questionnaire will be used for self-concept variables, Dolatabadi, Fatemeh (2007) questionnaire, and for physical screening, a checkerboard, plumb line, and flexible ruler will be used. There is a negative and significant relationship between the dimensions of upper limb anomalies and quality of life factors, and also there is a negative and significant relationship between the dimensions of upper limb anomalies and self-concept factors. The results showed that there is a negative and significant relationship between head and neck abnormalities with quality of life and self-concept factors, with a significance level of less than 0.05 in male students aged 7 to 10 years.

Keywords: upper limb erectile dysfunction, quality of life, self-concept, erectile abnormalities

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Authors: Mustapha A. Tijjani, Fanna I. Abdulrahman, Irfan Z. Khan, Umar K. Sandabe, Cong Li

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Air dried sample V. doniana after collection and identification was extracted with ethanol and further partition with chloroform, ethyl acetate and n-butanol. Ethanolic extract (11.9g) was fractionated on a silica gel accelerated column chromatography using solvents such as n-hexane, ethyl acetate and methanol. Each eluent fractions (150ml aliquots) were collected and monitored with thin layer chromatography. Fractions with similar Rf values from same solvents system were pooled together. Phytochemical test of all the fractions were performed using standard procedure. Complete elution yielded 48 fractions (150ml/fraction) which were pooled to 24 fractions base on the Rf values. It was further recombined and 12 fractions were obtained on the basis on Rf values and coded Vd1 to Vd12 fractions. Vd8 was further eluted with ethylacetate and methanol and gave fourteen sub fractions Vd8-a, -Vd8-m. Fraction Vd8-a (56mg) gave a white crystal compound coded V1. It was further checked on TLC and observed under ultraviolet lamp and was found to give a single spot. The Rf values were calculated to be 0.433. The melting point was determined using Gallenkamp capillary melting point apparatus and found to be 241-243°C uncorrected. Characterization of the isolated compound coded V1 was done using FT-infra-red spectroscopy, HNMR, 13CNMR(1and 2D) and HRESI-MS. The IR spectrum of compound V1 shows prominent peaks that corresponds to OHstr (3365cm-1) and C=0 (1652cm-1) etc. This spectrum suggests that among the functional moiety in compound V1 are the carbonyl and hydroxyl group. The 1H NMR (400 MHz) spectrum of compound V1 in DMSO-d6 displayed five singlet signals at δ 0.72 (3H, s, H-18), 0.79 (3H, s, H-19), 1.03 (3H, s, H-21), 1.04 (3H, s, H-26), 1.06 (3H, s, H-27) each integrating for three protons indicating the five methyl functional groups present in the compound. It further showed a broad singlet at δ 5.58 integrated for 1 H due to an olefinic H-atom adjacent to the carbonyl carbon atom. Three signals at δ 3.10 (d, J = 9.0 Hz, H-22), 3.59 (m, 1H, 2H-a) and 3.72 (m, 1H, 3H-e), each integrating for one proton is due to oxymethine protons indicating that three oxymethine H-atoms are present in the compound. These all signals are characteristic to the ecdysteroid skeletons. The 13C-NMR spectrum showed the presence of 27 carbon atoms, suggesting that may be steroid skeleton. The DEPT-135 experiment showed the presence of five CH3, eight CH2, and seven CH groups, and seven quaternary C-atoms. The molecular formula was established as C27H44O7 by high resolution electron spray ionization-mass spectroscopy (HRESI-MS) positive ion mode m/z 481.3179. The signals in mass spectrum are 463, 445, and 427 peaks corresponding to losses of one, two, three, or four water molecules characteristic for ecdysterone skeleton reported in the literature. Based on the spectral analysis (HNMR, 13CNMR, DEPT, HMQC, IR, HRESI-MS) the compound V1 is thus concluded to have ecdysteriod skeleton and conclusively conforms with 2β, 3β 14α, 20R, 22R, 25-hexahydroxy-5 β cholest-7-ene-6- one, or 2, 3, 14, 20, 22, 25 hexahydroxy cholest-7-ene-6-one commonly known as 20-hydroxyecdysone.

Keywords: vitex, phytochemical, purification, isolation, chromatography, spectroscopy

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Authors: Bonnie R. Brammall, Rhonda M. Garad, Helena J. Teede, Cheryce L. Harrison

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Introduction: Reproductive aged women are at high-risk for accelerated weight gain and obesity development, with pregnancy recognised as a critical contributory life phase. Healthy lifestyle interventions during the preconception and antenatal period improve maternal and infant health outcomes. Yet, interventions from preconception through to postpartum and translation and implementation into real-world healthcare settings remain limited. OptimalMe is a randomised, hybrid implementation effectiveness study of evidence-based healthy lifestyle intervention. Here, we report engagement, acceptability of the intervention during preconception, and self-reported behaviour change outcomes as a result of the preconception phase of the intervention. Methods: Reproductive aged women who upgraded their private health insurance to include pregnancy and birth cover, signalling a pregnancy intention, were invited to participate. Women received access to an online portal with preconception health and lifestyle modules, goal-setting and behaviour change tools, monthly SMS messages, and two coaching sessions (randomised to video or phone) prior to pregnancy. Results: Overall n=527 expressed interest in participating. Of these, n=33 did not meet inclusion criteria, n=8 were not contactable for eligibility screening, and n=177 failed to engage after the screening, leaving n=309 who were enrolled in OptimalMe and randomised to intervention delivery method. Engagement with coaching sessions dropped by 25% for session two, with no difference between intervention groups. Women had a mean (SD) age of 31.7 (4.3) years and, at baseline, a self-reported mean BMI of 25.7 (6.1) kg/m², with 55.8% (n=172) of a healthy BMI. Behaviour was sub-optimal with infrequent self-weighing (38.1%), alcohol consumption prevalent (57.1%), sub-optimal pre-pregnancy supplementation (61.5%), and incomplete medical screening. Post-intervention 73.2% of women reported engagement with a GP for preconception care and improved lifestyle behaviour (85.5%), since starting OptimalMe. Direct pre-and-post comparison of individual participant data showed that of 322 points of potential change (up-to-date cervical screening, elimination of high-risk behaviours [alcohol, drugs, smoking], uptake of preconception supplements and improved weighing habits) 158 (49.1%) points of change were achieved. Health coaching sessions were found to improve accountability and confidence, yet further personalisation and support were desired. Engagement with video and phone sessions was comparable, having similar impacts on behaviour change, and both methods were well accepted and increased women's accountability. Conclusion: A low-intensity digital health and lifestyle program with embedded health coaching can improve the uptake of preconception care and lead to self-reported behaviour change. This is the first program of its kind to reach an otherwise healthy population of women planning a pregnancy. Women who were otherwise healthy showed divergence from preconception health and lifestyle objectives and benefited from the intervention. OptimalMe shows promising results for population-based behaviour change interventions that can improve preconception lifestyle habits and increase engagement with clinical health care for pregnancy preparation.

Keywords: preconception, pregnancy, preventative health, weight gain prevention, self-management, behaviour change, digital health, telehealth, intervention, women's health

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Authors: B. O. Oyedoyin, M. O. Ilori, T. O. Oyebisi, B. A. Oluwale, O. O. Jegede

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The study was designed to evaluate the business development and transfer of technologies to small manufacturing companies by research institutes in South Western Nigeria. The study covered all the industrial research institutions with headquarters in South Western Nigeria. The study showed that the involvement of scientists in innovation process was rated highest in the idea generation (4.14) and idea screening (4.29) phases; high in R&D (3.86) and fairly high in pilot plant development (2.71) and commercialization (2.43) phase. Their involvement was rated low in business analysis and development (2.14), and test marketing (2.29) phase. The involvement of engineers was rated highest in idea generation (3.28), fairly high in R&D (2.71), pilot plant development (2.57), and idea screening (2.40) phases. However, their involvement was rated low in business analysis and development (2.0), test marketing (2.0), and commercialization (1.28) phases. The involvement of technology marketers in innovation process was generally rated fairly high in R&D (2.7) and business analysis and development (2.6), and low in all the other phases of innovation. However, their involvement at IAR&T, FIIRO, and NIOMR in all the phases was rated very high (3.0-5.0). The involvement of entrepreneurs was generally rated from fairly high to low (2.7-2.3) in all the phases of innovation. The involvement of financial institutions in all the phases of innovation was generally rated low (1.28-1.71). In conclusion, the study showed that the involvement of stakeholders like entrepreneurs and financial institutions in technology packaging for commercialization is very low.

Keywords: research institutes, national innovation system, Nigeria, entrepreneurs, financial institution

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Authors: D. Hilton

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An analysis of the Australian Diabetes Screening Study estimated undiagnosed diabetes mellitus [DM] prevalence in a high risk general practice based cohort. DM prevalence varied from 9.4% to 18.1% depending upon the diagnostic criteria utilised with age being a highly significant risk factor. Utilising the gold standard oral glucose tolerance test, the prevalence of DM was 22-23% in those aged >= 70 years and <15% in those aged 40-59 years. Opportunistic screening in Australian general practice potentially can identify many persons with undiagnosed type 2 DM. An Australian Bureau of Statistics document published three years ago, reported the highest rate of DM in men aged 65-74 years [19%] whereas the rate for women was highest in those over 75 years [13%]. If you consider that the Australian Bureau of Statistics report in 2007 found that 13% of the population was over 65 years of age and that this will increase to 23-25% by 2056 with a further projected increase to 25-28% by 2101, obviously this information has to be factored into the equation when age related diabetes prevalence predictions are calculated. This 10-15% proportional increase of elderly persons within the population demographics has dramatic implications for the estimated number of elderly persons with DM in these age groupings. Computational methodology showing the age related demographic changes reported in these official statistical documents will be done showing estimates for 2056 and 2101 for different age groups. This has relevance for future diabetes prevalence rates and shows that along with many countries worldwide Australia is facing an increasing pandemic. In contrast Japan is expected to have a decrease in the next twenty years in the number of persons with diabetes.

Keywords: epidemiological methods, aging, prevalence, diabetes mellitus

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Authors: Tomas Drevinskas, Ruta Mickiene, Audrius Maruska, Nicola Tiso, Algirdas Salomskas, Raimundas Lelesius, Agneta Karpovaite, Ona Ragazinskiene, Loreta Kubiliene

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Antiviral effect of substances accumulated by plants and natural products is known to ethno-pharmacy and modern day medicine. Antiviral properties are usually assigned to volatile compounds and polyphenols. This research work is divided into several parts and the task of this part was to investigate potential plants, potential substances and potential preparation conditions that can be used for the preparation of antiviral agents. Sixteen different medicinal plants, their parts and two types of propolis were selected for screening. Firstly, extraction conditions of non-volatile compounds were investigated: 3 pre-selected plants were extracted with 5 different ethanol – water mixtures (96%, 75%, 60%, 40%, 20 %, vol.) and bidistilled water. Total phenolic content, total flavonoid content and radical scavenging activity was determined. The results indicated that optimal extrahent is 40%, vol. of ethanol – water mixture. Further investigations were performed with the extrahent of 40%, vol. ethanol – water mixture. All 16 of selected plants, their parts and two types of propolis were extracted using selected extrahent. Determined total phenolic content, total flavonoid content and radical scavenging activity indicated that extracts of Origanum Vulgare L., Mentha piperita L., Geranium macrorrhizum L., Melissa officinalis L. and Desmodium canadence L. contains highest amount of extractable phenolic compounds (7.31, 5.48, 7.88, 8.02 and 7.16 rutin equivalents (mg/ ml) respectively), flavonoid content (2.14, 2.23, 2.49, 0.79 and 1.51 rutin equivalents (mg/ml) respectively) and radical scavenging activity (11.98, 8.72, 13.47, 13.22 and 12.22 rutin equivalents (mg/ml) respectively). Composition of the extracts is analyzed using HPLC.

Keywords: antiviral effect, plants, propolis, phenols

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Authors: J. E. O. Hernandez

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In the next 20 years, energy production by burning fuels will increase and so will the atmospheric concentration of CO2 and its well-known threats to life on Earth. The technologies available for capturing CO2 are still dubious and this keeps fostering an interest in bio-inspired approaches. The leading one is the application of carbonic anhydrase (CA) –a superfast biocatalyst able to convert up to one million molecules of CO2 into carbonates in water. However, natural CA underperforms when applied to real smoky CO2 in chimneys and, so far, the efforts to create superior CAs in the lab rely on screening methods running under pristine conditions at the micro level, which are far from resembling those in chimneys. For the evolution of man-made enzymes, selection rather than screening would be ideal but this is challenging because of the need for a suitable artificial environment that is also sustainable for our society. Herein we present the stepwise design and construction of a bioprocess (from bench-scale to semi-pilot) for evolutionary selection experiments. In this bioprocess, reaction and adsorption took place simultaneously at atmospheric pressure in a spray tower. The scrubbing solution was fed countercurrently by reusing municipal pressure and it was mainly prepared with water, carbonic anhydrase and calcium chloride. This bioprocess allowed for the enzymatic carbonation of smoky CO2; the reuse of process water and the recovery of solid carbonates without cooling of smoke, pretreatments, solvent amines and compression of CO2. The average yield of solid carbonates was 0.54 g min-1 or 12-fold the amount produced in serum bottles at lab bench scale. This bioprocess could be used as a tailor-made environment for driving the selection of superior CAs. The bioprocess and its match CA could be sustainably used to reduce global warming by CO2 emissions from exhausts.

Keywords: biological carbon capture and sequestration, carbonic anhydrase, directed evolution, global warming

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Authors: Nawaf A. Alqahtani, Ali M. Alqahtani, Khalid A. Alqahtani, Huda S. Abdullfattah, Ebtehal A. Alessa, Khalid S. Al Gelban, Ossama A. Mostafa

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Background: The internet is an exciting medium that is becoming an essential part of everyday life. Although the internet is fully observed in Saudi Arabia, young people may be vulnerable to problematic internet use, possibly leading to addiction. Aim of study: To explore the magnitude of internet addiction (IA) among medical students associated risk factors and its impact on students' academic achievement. Subjects and Methods: A cross sectional study was conducted in 2014 on 571 medical students (293 males and 278 females) at the College of Medicine, King Khalid University, Abha, Saudi Arabia. Data Collection was done through using the Arabic version of the Compulsive Internet Use Scale and a checklist of demographic characteristics. Results: Age of participants ranged from 19 to 26 years (Mean+SD: 21.9+1.5 years). Internet access was available to 97.4% of students at home and to 80.2% of students at their mobile phones. The most frequently accessed websites by medical students were the social media (90.7%), scientific website (50.4%) and the news websites (31.3%). IA was mild in 47.8% of medical students while 5.8% had moderate IA. None of the students had severe IA. Prevalence of IA was significantly higher among female medical students (p=0.002), availability of internet at home (p=0.022), and availability of internet at the students' mobile phone (p=0.041). The mean General Point Average (GPA) was highest among students with mild IA (4.0+0.6), compared with 3.6+0.6 among those with moderate addiction, and 3.9+0.6 among those who did not show IA. Differences in mean GPA according to grade of IA were statistically significant ((P=0.001). Conclusions: Prevalence of IA is high among medical students in Saudi Arabia. Risk factors for IA include female gender, availability of internet at home or at the mobile phone. IA has a significant impact on students' GPA. Periodic screening of medical students for IA and raising their awareness toward the possible risk of IA are recommended.

Keywords: internet addiction, medical students, risk factors, Saudi Arabia

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Authors: Nizar Ghali, Bernard Fortin, Guy Lacroix

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In Quebec, colonoscopies volumes have continued to rise in recent years in the absence of effective monitoring mechanism for the appropriateness and the quality of these exams. In 2010, November, Quebec Government introduced the colorectal cancer-screening program in the objective to control for volume and cost imperfection. This program is based on clinical standards and was initiated for first group of institutions. One year later, Government adds financial incentives for participants institutions. In this analysis, we want to assess for the causal effect of the two components of this program: clinical pathways and financial incentives. Especially we assess for the reform effect on healthcare quality and population health in the context that medical remuneration is not directly dependent on this additional funding offered by the program. We have data on admissions episodes and deaths for 8 years. We use multistate model analog to difference in difference approach to estimate reform effect on the transition probability between different states for each patient. Our results show that the reform reduced length of stay without deterioration in hospital mortality or readmission rate. In the other hand, the program contributed to decrease the hospitalization rate and a less invasive treatment approach for colorectal surgeries. This is a sign of healthcare quality and population health improvement. We demonstrate in this analysis that physicians’ behavior can be affected by both clinical standards and financial incentives even if offered to facilities.

Keywords: multi-state and multi-episode transition model, healthcare quality, length of stay, transition probability, difference in difference

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Authors: Vagolu S. Krishna, Shan Zheng, Estharla M. Rekha, Luke W. Guddat, Dharmarajan Sriram

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Tuberculosis (TB) remains a major threat to human health. This due to the fact that current drug treatments are less than optimal as well as the rising occurrence of multi drug-resistant and extensively drug-resistant strains of the etiological agent, Mycobacterium tuberculosis (Mt). Given the wide-spread significance of this disease, we have undertaken a design and evaluation program to discover new anti-TB drug leads. Here, our attention is focused on ketol-acid reductoisomerase (KARI), the second enzyme in the branched-chain amino acid biosynthesis pathway. Importantly, this enzyme is present in bacteria but not in humans, making it an attractive proposition for drug discovery. In the present work, we used high-throughput virtual screening to identify seventeen potential inhibitors of KARI using the Birla Institute of Technology and Science in-house database. Compounds were selected based on high docking scores, which were assigned as the result of favourable interactions between the compound and the active site of KARI. The Ki values for two leads, compounds 14 and 16 are 3.71 and 3.06 µM, respectively for Mt KARI. To assess the mode of binding, 100 ns molecular dynamics simulations for these two compounds in association with Mt KARI were performed and showed that the complex was stable with an average RMSD of less than 2.5 Å for all atoms. Compound 16 showed an MIC of 2.06 ± 0.91 µM and a 1.9 fold logarithmic reduction in the growth of Mt in an infected macrophage model. The two compounds exhibited low toxicity against murine macrophage RAW 264.7 cell lines. Thus, both compounds are promising candidates for development as an anti-TB drug leads.

Keywords: ketol-acid reductoisomerase, macrophage, molecular docking and dynamics, tuberculosis

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Authors: Ait Slimane-Ait Kaki Sabrina, Foudi Lamia

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The present work consists of the study of the bio-ecology and the therapeutic effects of the belladone (Atropa belladonna L.). It is a medicinal plant of the Solanacées family, herbaceous, robust 0.5 up to 1.50 m high. The phytochemical analysis of leaves revealed alkaloids, tannins, catechin, coumarins, mucilages, saponins, starch, and reducing compounds. The experimental study concerns the extraction and characterization of belladonna alkaloids. Analysis of the purified extract by staining tests confirmed the presence of tropane alkaloids. The dosage chromatography revealed the presence of components that have been identified atropine, scopolamine and hyoscyamine. Evaluation of antimicrobial and antifungal alkaloids from the methanol extract and aqueous extract of belladonna on pathogenic germs showed a positive bactericidal against strains of Escherichia coli and Staphylococcus aureus. Our preliminary results allow us an overall assessment of the medicinal value of Atropa belladonna.

Keywords: belladone, alkaloid, antibacterial activity, antifungal activity

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Authors: Nargiza Nuralieva

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The study delves into assessing the influence of mindfulness and mental resilience training on the cognitive performance and stress management of pilots. Employing a meticulous literature search across databases such as Medline and Google Scholar, the study used specific keywords to target a wide array of studies. Inclusion criteria were stringent, focusing on peer-reviewed studies in English that utilized designs like randomized controlled trials, with a specific interest in interventions related to mindfulness or mental resilience training for pilots and measured outcomes pertaining to cognitive performance and stress management. The initial literature search identified a pool of 123 articles, with subsequent screening resulting in the exclusion of 77 based on title and abstract. The remaining 54 articles underwent a more rigorous full-text screening, leading to the exclusion of 41. Additionally, five studies were selected from the World Health Organization's clinical trials database. A total of 11 articles from meta-analyses were retained for examination, underscoring the study's dedication to a meticulous and robust inclusion process. The interventions varied widely, incorporating mixed approaches, Cognitive behavioral Therapy (CBT)-based, and mindfulness-based techniques. The analysis uncovered positive effects across these interventions. Specifically, mixed interventions demonstrated a Standardized Mean Difference (SMD) of 0.54, CBT-based interventions showed an SMD of 0.29, and mindfulness-based interventions exhibited an SMD of 0.43. Long-term effects at a 6-month follow-up suggested sustained impacts for both mindfulness-based (SMD: 0.63) and CBT-based interventions (SMD: 0.73), albeit with notable heterogeneity.

Keywords: mindfulness, mental resilience, pilots, cognitive performance, stress management

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Authors: Ahmed El-Ghorab

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Indigenous foods are promising sources of various chemical bioactive compounds such as vitamins, phenolic compounds and carotenoids. Therefore, the presence o different bioactive compounds in fruits could be used to retard or prevent various diseases such as cardiovascular and cancer. This is an update report on nutritional compositions and health promoting phytochemicals of different indigenous food . This different type of fruits and/ or other sources such as spices, aromatic plants, grains by-products, which containing bioactive compounds might be used as functional foods or for nutraceutical purposes. most common bioactive compounds are vitamin C, polyphenol, β- carotene and lycopene contents. In recent years, there has been a global trend toward the use of natural phytochemical as antioxidants and functional ingredients, which are present in natural resources such as vegetables, fruits, oilseeds and herbs.. Our future trend the Use of Natural antioxidants as a promising alternative to use of synthetic antioxidants and the Production of natural antioxidant on commercial scale to maximize the value addition of indigenous food waste as a good source of bioactive compounds such as antioxidants.

Keywords: bioactive compounds, antioxidants, by-product, indigenous foods, phenolic compounds

Procedia PDF Downloads 452

Authors: Kai-Jui Kou, Tzu-Ling Shen, Ying-Fang Wang

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The objectives of the present study are to characterize nanoparticles generated from the different working type in 3D printing room and the stack flue during 3D printing process. The studied laboratory (10.5 m× 7.2 m × 3.2 m) with a ventilation rate of 500 m³/H is installed a 3D metal printing machine. Direct-reading instrument of a scanning mobility particle sizer (SMPS, Model 3082, TSI Inc., St. Paul, MN, USA) was used to conduct static sampling for nanoparticle number concentration and particle size distribution measurements. The SMPS obtained particle number concentration at every 3 minutes, the diameter of the SMPS ranged from 11~372 nm when the aerosol and sheath flow rates were set at 0.6 and 6 L/min, respectively. The concentrations of background, printing process, clearing operation, and screening operation were performed in the laboratory. On the other hand, we also conducted nanoparticle measurement on the 3D printing machine's stack flue to understand its emission characteristics. Results show that the nanoparticles emitted from the different operation process were the same distribution in the form of the uni-modal with number median diameter (NMD) as approximately 28.3 nm to 29.6 nm. The number concentrations of nanoparticles were 2.55×10³ count/cm³ in laboratory background, 2.19×10³ count/cm³ during printing process, 2.29×10³ count/cm³ during clearing process, 3.05×10³ count/cm³ during screening process, 2.69×10³ count/cm³ in laboratory background after printing process, and 6.75×10³ outside laboratory, respectively. We found that there are no emission nanoparticles during the printing process. However, the number concentration of stack flue nanoparticles in the ongoing print is 1.13×10⁶ count/cm³, and that of the non-printing is 1.63×10⁴ count/cm³, with a NMD of 458 nm and 29.4 nm, respectively. It can be confirmed that the measured particle size belongs to easily penetrate the filter in theory during the printing process, even though the 3D printer has a high-efficiency filtration device. Therefore, it is recommended that the stack flue of the 3D printer would be equipped with an appropriate dust collection device to prevent the operators from exposing these hazardous particles.

Keywords: nanoparticle, particle emission, 3D printing, number concentration

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Authors: Matei Tudor Berceanu, Hema Viswambharan, Kirti Kain, Chew Weng Cheng

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Background - Obesity parameters, particularly visceral obesity as measured by the waist-to-height ratio (WHtR), correlate with insulin resistance. The metabolic microvascular changes associated with insulin resistance causes increased peripheral arteriolar resistance primarily to the lower limb vessels. We hypothesize that ankle systolic blood pressures (SBPs) are more significantly associated with visceral obesity than brachial SBPs. Methods - 1098 adults enriched in south Asians or Europeans with diabetes (T2DM) were recruited from a primary care practice in West Yorkshire. Their medical histories, including T2DM and cardiovascular disease (CVD) status, were gathered from an electronic database. The brachial, dorsalis pedis, and posterior tibial SBPs were measured using a Doppler machine. Their body mass index (BMI) and WHtR were calculated after measuring their weight, height, and waist circumference. Linear regressions were performed between the 6 SBPs and both obesity parameters, after adjusting for covariates. Results - Generally, the left posterior tibial SBP (P=4.559*10⁻¹⁵) and right posterior tibial SBP (P=1.114* 10⁻¹³ ) are the pressures most significantly associated with the BMI, as well as in south Asians (P < 0.001) and Europeans (P < 0.001) specifically. In South Asians, although the left (P=0.032) and right brachial SBP (P=0.045) were associated to the WHtR, the left posterior tibial SBP (P=0.023) showed the strongest association. Conclusion - Regardless of ethnicity, ankle SBPs are more significantly associated with generalized obesity than brachial SBPs, suggesting their screening potential for screening for early detection of T2DM and CVD. A combination of ankle SBPs with WHtR is proposed in south Asians.

Keywords: ankle blood pressures, body mass index, insulin resistance, waist-to-height-ratio

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Authors: Ashwinder K. Dhaliwal, G. P. S. Dhillon

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Eucalyptus is one of the most important forest tree species that can tolerate and grow well on degraded and unfertile soils which are not suitable for other tree species. Besides this, these trees have a short rotation and good economic value. However, the gall inducing wasp Leptocybe invasa Fisher and La Salle has been reported from many countries throughout the world. The spread of L. invasa is of huge economic concern as more than 20,000 ha of young Eucalyptus trees have already been affected in southern states of India. The host plant resistance being the first line of defense against insect pests demands the screening of different germplasm source against L. invasa. Keeping this in view, fourteen different clones of Eucalyptus spp. were evaluated for their susceptibility to L. invasa from a replicated clonal trial planted at Punjab Agricultural University, Ludhiana. The degree of gall infestation was recorded from three plants of each clone in each replication. Three branches selected from the lower, middle and upper canopy of the trees were selected for recording the total number of galls induced by L. invasa. The statistical analysis was done as per the procedure laid down for completely randomised block design (CRBD), analysis of variance (ANOVA), critical difference (CD) and variance components using Proc GLM (SAS software 9.3, SAS Institute Ltd. U.S.A). All possible treatment means were compared with Duncan’s multiple range test (DMRT) at 1 % probability level. The results showed that the clones C-9, C-45 and C-42 were completely free from the infestation of L. invasa. However, there was minor infestation of L. invasa on C-2135, C-413, C-407, C-35, C-72 and C-37 clones. The clone C-6 was severely infested by L. invasa followed by C-11, C-12, F-316 and C-25 clones. The information generated by this study will be helpful for future breeding and use in afforestation programmes.

Keywords: eucalyptus clones, gall wasp, Leptocybe invasa, screening, susceptibility

Procedia PDF Downloads 197

Authors: Muhammad Solikhudin Nafi, Wahyu Afif Mufida, Mita Erna Wati, Fitri Setyani Rokim, M. Al-Rizqi Dharma Fauzi

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High dose activity without any pre-exercise will impact Delayed Onset Muscle Soreness (DOMS). DOMS known as delayed pain post-exercise and induce skeletal injury which will decrease athletes’ performances. From now on, post-exercise muscle damage can be detected by measuring skeletal troponin I (sTnI) concentration in serum using ELISA but this method needs more time and cost. To prevent decreased athletes performances, screening need to be done rapidly. We want to introduce our new prototype to detect DOMS acutely. Rapid detection tests are based on immunological reaction between skeletal troponin I antibodies and sTnI in human serum or whole blood. Chemical methods that are used in the manufacture of diagnostic test is lateral flow immunoassay. The material used is rat monoclonal antibody sTnI, colloidal gold, anti-mouse IgG, nitrocellulose membrane, conjugate pad, sample pad, wick and backing card. The procedure are made conjugate (colloidal gold and mAb sTnI) and insert into the conjugate pad, gives spray sTnI mAb and anti-mouse IgG into nitrocellulose membrane, and assemble RDT. RDT had been evaluated by measuring the sensitivity of positive human serum (n = 30) and negative human serum (n = 30). Overall sensitivity value was 93% and specificity value was 90%. ADCOR as the first rapid detection test qualitatively showed antigen-antibody reaction and showed good overall performances for screening of muscle damage. Furthermore, these finding still need more improvements to get best results.

Keywords: DOMS, sTnI, rapid detection test, ELISA

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Authors: Nisha Harry, Keshia Sing

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Orientation: The Multifactor Leadership Questionnaire (MLF) and the sense of coherence-29 (SCS) is an effective tools to assess the prevalence and underlying structures of empirically based taxonomies related to leadership and wellbeing. Research purpose: The purpose of the study was to test the psychometric properties of the SCS and Multifactor Leadership Questionnaire (MLQ) to screen for psychological wellness indices within the banking industry in South Africa. Motivation for the study: The contribution of these two instruments for the purpose of determining psychological wellness in a banking work environment is unique. Research design, approach, or method: The sample consisted of (N = 150) financial staff employed in a South African banking organisation. The age of the sample was: 37% (30 -40 yrs), 31% (20-30 yrs), 26% (40- 50 yrs), and 6% (50+yrs), of which 52% were males, 48% were females. The white race group was the majority at 29%, African at 26%, Coloured at 23%, and Indian was 22%. Main findings: Results from the exploratory factor analysis revealed a two-factor structure as the most satisfactory. Confirmatory factor analyses revealed the two-factor model displayed better good of-fit indices. Practical implications: The factor structure of the Sense of Coherence-29 scale (SCS), and the Multifactor Leadership Questionnaire (MLQ), have a value-added focus to determine psychological wellness within banking staff. It is essential to take into account these constructs when developing employee wellness interventions. Contribution/value add: Understanding the psychometric properties of the SCS, the self-reported form, and the MLQ questionnaire contributes to screening psychological wellness indices such as coping within the banking industry in a developing country like South Africa. Leaders are an important part of the implementation process of organisational employee wellness practices.

Keywords: factorial structure, leadership, measurement invariance, psychological wellness, sense of coherence

Procedia PDF Downloads 78