Search results for: infectious salmon anemia virus

Authors: Grienggrai Rajchakit

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As we all know that coronavirus is announced as a pandemic in the world by WHO. It is speeded all over the world with few days of time. To control this spreading, every citizen maintains social distance and self-preventive measures are the best strategies. As of now, many researchers and scientists are continuing their research in finding out the exact vaccine. The machine learning model finds that the coronavirus disease behaves in an exponential manner. To abolish the consequence of this pandemic, an efficient step should be taken to analyze this disease. In this paper, a recurrent neural network model is chosen to predict the number of active cases in a particular state. To make this prediction of active cases, we need a database. The database of COVID-19 is downloaded from the KAGGLE website and is analyzed by applying a recurrent LSTM neural network with univariant features to predict the number of active cases of patients suffering from the corona virus. The downloaded database is divided into training and testing the chosen neural network model. The model is trained with the training data set and tested with a testing dataset to predict the number of active cases in a particular state; here, we have concentrated on Andhra Pradesh state.

Keywords: COVID-19, coronavirus, KAGGLE, LSTM neural network, machine learning

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Authors: Wenxiao Liu, Kun Zhang, Yongqing Li

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Bovine herpesvirus 1, a member of the genus Variellovirus of the subfamily Alphaherpesvirinae, has caused severe economic cost to the bovine industry. In this study, BoHV-1 glycerol protein gD was expressed in insect cells, and the purified gD was immunized in the Balb/C mice to generate monoclonal antibodies. Based on hybridoma cell fusion techniques, 20 monoclonal antibodies against Bovine herpesvirus 1 have been obtained. Further, mAb 3F8 with neutralizing activity and gD were applied to develop a blocking enzyme-linked immunosorbent assay (Elisa) for detecting neutralizing antibodies against BoHV-1, which shows a significant correlation between the blocking Elisa and VNT. The sensitivity and specificity of the test were estimated to be 94.59% and 93.42%, respectively. Furthermore, antibody pairing tests revealed that mAb 1B6 conjugated to fluorescence microspheres was used as the capture antibody, and mAb 3F9 was used as the detectable antibody to establish the immunochromatographic assay (ICS). The ICS was conducted to detect BoHV-1 in bovine samples with high sensitivity, specificity, and good stability. Clinical sample testing revealed that the results of ICS and real-time PCR have a coincidence rate of 95.42%. Our research confirmed that the ICS is a rapid and reliable method for the diagnosis of BoHV-1. In conclusion, our results lay a solid foundation for the prevention and control of BoHV-1 infection.

Keywords: bovine disease, BoHV-1, ELISA, ICS assay

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Authors: Harukuni Tokuda, Xu FengHao, Nobutaka Suzuki

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As part of an ongoing our projects to investigate the anti-tumor promoring properties (chemopreventive potency) of Gromwell seed, dry powder materials and its active compounds were carried out through useful test systems. Gromwell seed (Coix lachryma-jobi seed) (GS) is a grass crop that has long been used and played a role in traditional medicine as a nourishing food, and for the treatment of various aliments, paticularly cancer. The application of a new screening procedure which utilizes the synergistic effect of short-chain fatty acids and phorbol esters in enable rapid and easy detection of naturally occurring substances(anti-tumor promoters chemo-preventive agents) with inhibition of Epstein-Barr virus(EBV) activation, using human lymphblastoid cells. In addition, we have now extended these investigations to a new tumorigenesis model in which we initiated the tumors with DMBA intiation and promoted with 1.7 nmol of TPA in two-stage mouse skin test and other models. these results provide a basis for further development of these botanical supplements for human cancer chemoprevention and observations seem that this materials more extensively as one of the trials for the purpose of complementary and alternative medicine.

Keywords: chemoprevention, medicinal plant, mouse, carcinogenesis systems

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Authors: Woraprat Amnuaychaichana

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Several medicinal plants are well known to contain active constituents such as flavonoids and phenolic compounds with are plausible candidates for therapeutic purposes. An infectious disease caused by microbial infection is the leading cause of death. Antibiotics are typically used to eradicate these microbes, but recent evidence indicates that they are developing antibiotic-resistant effects. This study focused on antimicrobial activities of Phyllanthus emblica and Gracilaria fisheri using the agar disk diffusion method and broth microdilution to determine the minimum inhibitory concentration (MIC) value. The extracts were screened against Staphylococcus aureus. Five concentrations of plant extracts were used to determine the minimum inhibitory concentration (MIC) by 2-fold dilution of plant extract. The results indicated that G. fisheri extract gave the maximum zones of inhibition of 11.7 mm against S. aureus while P. emblica showed no effects. The MIC values of G. fisheri extract against S. aureus was 500 µg/ml. To summarise, G. fisheri extracts demonstrated high efficacy of antibacterial activity against Gram-positive S. aureus, which may pave the way for developing a formulation containing this plant. G. fisheri extract should be subjected to additional investigation in order to determine the mechanism of action of its antimicrobial activity.

Keywords: antibacterial activity, Staphylococcus aureus, gracilaria fishery, Phyllanthus emblica

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Authors: N. Benahmed, A. Cheriti

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Kidney stones of infectious origin, in particular, the phosphate amoniaco-magnesian hexahydrate or struvite are one of the risk factors that most often leads of renal insufficiency. Many plants species, described in pharmacopoeias of several countries is used as a remedy for urinary stones, the latter is a disease resulting from the presence of stones in the kidneys or urinary tract. Our research is based on the existing relationship between the effect of extracts of medicinal plant used for the cure of urinary tract diseases in the region of Algeria south-west on urolithiasis especially Ammonium-Magnesium Phosphate Hexahydrate (Struvite). We have selected Zea mays L. (POACEAE) for this study. On the first stage, we have studied the crystallisation of struvite 'in vitro' without inhibitors, after we have compared to crystallization with inhibitors. Most of The organic and aqueous extracts of this plant give an effect on the crystal size of struvite. It is a very significant reduction in the size of the crystals of struvite in the presence of hexane and ethanol extract (12 to 5-6 μm). We’ve observed a decrease in the size of the aggregates in the presence of all the extracts. This reduction is important for the aqueous, acetone and chloroform extract (45 to 10-16μm). Finally, a deep study was conducted on the effective extract of Zea mays L.; for determine the influence of inhibitory phytochemical compounds.

Keywords: medicinal plants, struvite, urolithiasis, zea mays

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Authors: Asma Hanif, A. I. K. Butt, Shabir Ahmad, Rahim Ud Din, Mustafa Inc

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This paper is devoted to a study of the fuzzy fractional mathematical model reviewing the transmission dynamics of the infectious disease Covid-19. The proposed dynamical model consists of susceptible, exposed, symptomatic, asymptomatic, quarantine, hospitalized and recovered compartments. In this study, we deal with the fuzzy fractional model defined in Caputo’s sense. We show the positivity of state variables that all the state variables that represent different compartments of the model are positive. Using Gronwall inequality, we show that the solution of the model is bounded. Using the notion of the next-generation matrix, we find the basic reproduction number of the model. We demonstrate the local and global stability of the equilibrium point by using the concept of Castillo-Chavez and Lyapunov theory with the Lasalle invariant principle, respectively. We present the results that reveal the existence and uniqueness of the solution of the considered model through the fixed point theorem of Schauder and Banach. Using the fuzzy hybrid Laplace method, we acquire the approximate solution of the proposed model. The results are graphically presented via MATLAB-17.

Keywords: Caputo fractional derivative, existence and uniqueness, gronwall inequality, Lyapunov theory

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Authors: B. Waked Najar

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Since the spread of Covid- 19, Israel and other countries suffer from lockdowns and social distance, which impose different kinds of restrictions. On the one side, many organization closed and unemployment increased, bringing about economic problems and distress. On the other side, family ties were damaged due to inability to sustain close relations with some family members and too frequent interactions with others. Unfortunately, conflicts within families, controlling behavior and domestic violence appear more often. Purpose: to examine the phenomenon of domestic violence and its expansion during the Covid-19 crisis, to propose and classify strategies of dealing with it, including encouragement of public systems providing more information and support to domestic violence victims. Methodology: the author strives to reveal methods of supporting domestic violence victims through public and private treatment organizations. The author interviewed battered women and families who experienced violence during the Covid-19 crisis. Findings: victims of domestic violence often feel isolated and helpless. It is a real challenge to track and support them, especially in the traditional minorities’ communities. Research limitations: Many families refused to be interviewed because they did not want to be exposed to the community, especially religious families. Originality: research is aimed to examine a phenomenon of domestic violence during the Covid-19 crisis and methods of help and support the victims, which is not a common theme of research during the pandemic.

Keywords: violence, coronavirus, domestic violence, influence

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Authors: Dzatur Rizqi Fathienah Syarifuddin, Isharyah Sunarno, Eddy Hartono, Siti Maisuri T. Chalid

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Introduction: The potential impact of coronavirus disease 2019 (COVID-19) on the health of expectant mothers and fetuses has strained attention. Pregnant women are considered a vulnerable category to respiratory infections. Moreover, several inflammatory cytokines are 2-100 times more abundant in COVID-19 with cytokine storms than in normal individuals; interleukin 6 (IL-6) exhibits much higher elevations. Investigating potential relationships between IL-6 serum levels and the severity of COVID-19 symptoms in pregnant women is the aim of this study. Material and Methods: Sixty-two eligible pregnant women were divided into a positive COVID-19 group (n=31) and a negative COVID-19 group (n=31) in this cross-sectional study. The research subjects were selected using consecutive sampling. The IL-6 was measured from a vein blood specimen using ELISA methods. Results: The COVID-19 positive group had a higher median IL-6 serum level (45.35 (35.15- 153.99) vs. 38.86 ± 11.43 (15.02-59.52), p=0.03) than the negative group. On the other hand, the IL-6 serum level had comparable value according to the COVID-19 symptoms severity (88.35 ± 36.14 ng/mL vs. 51.09 ± 25.48 ng/mL vs. 56.02 ± 33.20 ng/mL in moderate symptoms, mild symptoms, and asymptomatic, respectively; p=0.152). Conclusion: Although the IL-6 serum levels are not related to COVID-19 symptoms severity, an elevated of this biomarker was found in pregnant women with affected diagnoses.

Keywords: interleukin-6, pregnancy, COVID-19, several inflammatory

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Authors: Azhar Jabareen, Mahmoud Huleihel

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BRCA-1 is a multifunctional tumor suppressor, whose expression is activated by the estrogen (E2)-liganded ERα receptor. The activated ERα is a transcriptional factor which activates various genes either by direct binding to the DNA at E2-responsive elements (EREs) and indirectly associated with a range of alternative non-ERE elements. Interference with BRCA-1 expression and/or functions leads to high risk of breast or/and ovarian cancer. Our lab investigated the involvement of Human T-cell leukemia Virus Type 1 (HTLV-1) in breast cancer, since HTLV-1 Tax was found to strongly inhibit BRCA-1 expression. In addition, long exposure of 12-O-tetradecanoylphorbol-13-acetate (TPA), which is one of the stress-inducing agents activated the HTLV-1 promoter. So here the involvement of TPA in breast cancer had been examined by testing the effect of TPA on BRCA-1 and ERE expression. The results showed that TPA activated both BRCA-1 and ERE expression. In the 12 hours TPA activated the tow promoters more than others time, and after 24 hours the level of the tow promoters was decreased. Tax inhibited BRCA-1 expression but did not succeed to inhibit the effect of TPA. Then the activation of the two promoters was not through ERα pathway because TPA had no effect on ERα binding to the two promoters of the BRCA-1 and ERE. Also, the activation was not via nuclear factor kappa B (NF-κB) pathway because when the inhibitory of NF-κB had been added to the TPA, it still activated the tow promoters. However, it seems that 53BP1 may be involved in TPA activation of these promoters because ectopic high expression of 53BP1 significantly reduced the TPA activity. In addition, in the presence of Bisindolylmaleimide-I (BI)- the inhibitor of Protein Kinase C (PKC)- there was no activation for the two promoters, so the PKC is agonized BRCA-1 and ERE activation.

Keywords: BRCA-1, ERE, HTLV-1, TPA

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Authors: Fern Baedyananda, Arkom Chaiwongkot, Somchai Niruthisard, Nakarin Kitkumthorn, Parvapan Bhattarakosol

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High-risk human papillomavirus (HPV) infections cause transformation of the host cells by down-regulating and inhibiting host regulatory proteins such as p53 and pRb by overexpressing the viral oncoproteins E6 and E7. However, the E1 protein which is the only enzyme encoded by HPV has also been shown to cause DNA instability leading to the integration of the virus into the host genome and triggering carcinogenic events. A 63bp duplication in the E1 helicase region has been detected in European patients. However, the clinical prognosis of these patients is still controversial. This study was performed to determine the presence of the HPV-16 E1 63bp duplication in patient cervical samples in Thai women and determine the sequence of the variant in the Thai population. Detection of the HPV-16 E1 duplication in the helicase region was performed in 90 patient cell samples across normal, cervical intraepithelial neoplasia I-III, and squamous cervical carcinoma stages by PCR. The PCR products were purified and sequenced to determine the presence of duplication variants.The variant form was found in 10% of all CIN 1 patients. In this study, the presence of the 63 bp duplication variant in the Thai population was found to be present and was further characterized. Interestingly, all samples that exhibited the variant form of HPV-16 E1 were classified as CIN I. Presence of the variant, constricted to mild dysplasia signifies the importance of HPV-16 E1 in carcinogenesis.

Keywords: carcinogenesis, cervical cancer, human papillomavirus, HPV-16 E1

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Authors: Hatem A. El-Mezayen, Hossam Darwesh

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Background/Aim: Hepatocellular carcinoma (HCC) is often diagnosed at advanced stage where effective therapies are lacking. Identification of new scoring system is needed to discriminate HCC patients from those with chronic liver disease. Based on the link between vascular endothelial growth factor (VEGF) and HCC progression, we aimed to develop a novel score based on combination of VEGF and routine laboratory tests for early prediction of HCC. Methods: VEGF was assayed for HCC group (123), liver cirrhosis group (210) and control group (50) by Enzyme Linked Immunosorbent Assay (ELISA). Data from all groups were retrospectively analyzed including α feto protein (AFP), international normalized ratio (INR), albumin and platelet count, transaminases, and age. Areas under ROC curve were used to develop the score. Results: A novel index named hepatocellular carcinoma-vascular endothelial growth factor score (HCC-VEGF score)=1.26 (numerical constant) + 0.05 ×AFP (U L-1)+0.038 × VEGF(ng ml-1)+0.004× INR –1.02 × Albumin (g l-1)–0.002 × Platelet count × 109 l-1 was developed. HCC-VEGF score produce area under ROC curve of 0.98 for discriminating HCC patients from liver cirrhosis with sensitivity of 91% and specificity of 82% at cut-off 4.4 (ie less than 4.4 considered cirrhosis and greater than 4.4 considered HCC). Conclusion: Hepatocellular carcinoma-VEGF score could replace AFP in HCC screening and follow up of cirrhotic patients.

Keywords: Hepatocellular carcinoma, cirrhosis, HCV, diagnosis, tumor markers

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Authors: Ajit Kumar Yadav, Priyanka Yadav, F. Ram

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In present study is an effort to analyse the burden of diseases in the state. Disability Adjusted Life Years (DALY) is estimated non-communicable diseases. Multi-rounds (52nd, 60th and 71st round) of the National Sample Surveys (NSSO), conducted in 1995-96, 2004 and 2014 respectively, and Million Deaths Study (MDS) of 2001-03, 2006 and 2013-14 datasets are used. Descriptive and multivariate analyses are carried out to identify the determinants of different types of self-reported morbidity and DALY. The prevalence was higher for population aged 60 and above, among females, illiterates, and rich across the time period and for all the selected morbidities. The results were found to be significant at P<0.001. The estimation of DALY revealed that, the burden of communicable diseases was higher during infancy, noticeably among males than females in 2002. However, females aged 1-5 years were more vulnerable to report communicable diseases than the corresponding males. The age distribution of DALY indicates that individuals aged below 5 years and above 60 year were more susceptible to ill health. The growing incidence of non-communicable diseases especially among the older generations put additional burden on the health system in the state. The state has to grapple with the unsettled preventable infectious diseases in one hand and growing non-communicable in other hand.

Keywords: disease burden, non-communicable, communicable, India and region

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Authors: Aml M. El-Sharkawy, Hossam M. Darwesh

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Abstract— Background/Aim: Hepatocellular carcinoma (HCC) is often diagnosed at advanced stage where effective therapies are lacking. Identification of new scoring system is needed to discriminate HCC patients from those with chronic liver disease. Based on the link between tumor associated trypsin inhibitor (TATI) and HCC progression, we aimed to develop a novel score based on combination of TATI and routine laboratory tests for early prediction of HCC. Methods: TATI was assayed for HCC group (123), liver cirrhosis group (210) and control group (50) by Enzyme Linked Immunosorbent Assay (ELISA). Data from all groups were retrospectively analyzed including α feto protein (AFP), international normalized ratio (INR), albumin and platelet count, transaminases, and age. Areas under ROC curve were used to develop the score. Results: A novel index named hepatocellular carcinoma-vascular endothelial growth factor score (HCC-TATI score) = 3.1 (numerical constant) + 0.09 ×AFP (U L-1) + 0.067 × TATI (ng ml-1) + 0.16 × INR – 1.17 × Albumin (g l-1) – 0.032 × Platelet count × 109 l-1 was developed. HCC-TATI score produce area under ROC curve of 0.98 for discriminating HCC patients from liver cirrhosis with sensitivity of 91% and specificity of 82% at cut-off 6.5 (ie less than 6.5 considered cirrhosis and greater than 4.4 considered HCC). Conclusion: Hepatocellular carcinoma-TATI score could replace AFP in HCC screening and follow up of cirrhotic patients.

Keywords: Hepatocellular carcinoma, cirrhosis, HCV, diagnosis, TATI

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Authors: Seyed Mehrzad Pahlavani, Mozaffar Haji Jafari Anaraki, Sayma Mohammadi

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A total of 34700 day-old broilers were exposed to green, blue and yellow light using a light-emitting diode system for 6 weeks to investigate the effects of light wave length on antibody responses to Newcastle disease by HI test and the correlation with ELISA. 3 poultry house broiler farms with the same conditions was selected and the lightening system of each was set according to the requirement. Blood samples were taken from 20 chicks on days 1, 24 and 46 and the Newcastle virus specific antibody was titered in serum using HI an ELISA test. On day 24, the probability value of more than 0/05 was observed in HI and ELISA tests of all groups while at the end of breeding period, the average HI serum antibody titer was more in the green light than the yellow one while the blue light was not significantly different from both. At the last titration, the green light has got the highest titer of Newcastle antibodies. There were no significant differences of Newcastle antibody titers between all groups and ages in broiler pullets in ELISA. According to the sampling and analysis of HI and ELISA serum tests, there were no significant relationships between all broiler pullets breeding in green, blue and yellow light on days 24 and 46 and the P-value was more than 0/05. It is suggested that the monochromatic light is effective on broilers immunity against Newcastle disease.

Keywords: monochromatic light, Newcastle disease, HI test, ELISA test

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Authors: Ali Oztuna, Meral Sarper, Deniz Torun, Fatma Bayrakdar, Selcuk Kilic, Mehmet Baysallar

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Bacillus anthracis is one of the biological agents most likely to be used in case of bioterrorist attack as well as being the cause of anthrax. The bacterium's major virulence factors are the anthrax toxins and an antiphagocytic polyglutamic capsule. TEM8 (ANTXR1) and CMG2 (ANTXR2) are ubiquitously expressed type I transmembrane proteins, and ANTXR2 is the major receptor for anthrax toxins. MicroRNAs are 21-24 bp small noncoding RNAs that regulate gene expression by base pairing with the 3' UTR (untranslated regions) of their target mRNAs resulting in mRNA degradation and/or translational repression. MicroRNAs contribute to regulation of most biological processes and influence numerous pathological states like infectious disease. In this study, post-exposure (toxins) protective effect of the hsa-miR-124-3p against Bacillus anthracis was examined. In this context, i) THP-1 and U937 cells were differentiated to MΦ macrophage, ii) miRNA transfection efficiencies were evaluated by flow cytometry and qPCR, iii) protection against Bacillus anthracis toxins were investigated by XTT, cAMP ELISA and MEK2 cleavage assays. Acknowledgements: This work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) under Grant SBAG-218S467.

Keywords: ANTXR2, hsa-miR-124-3p, MΦ macrophage, THP-1, U937

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Authors: Osama H. Elsayed, Mohsen M. S. Asker, Mahmoud A. Swelim, Ibrahim H. Abbas, Aziza I. Attwa, Mohamed E. El Awady

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Hydroxy marilone C is a bioactive metabolite was produced from the culture broth of Streptomyces badius isolated from Egyptian soil. hydroxy marilone C was purified and fractionated by silica gel column with a gradient mobile phase dicloromethane (DCM) : Methanol then Sephadex LH-20 column using methanol as a mobile phase. It was subjected to many instruments as Infrared (IR), nuclear magnetic resonance (NMR), Mass spectroscopy (MS) and UV spectroscopy to the elucidation of its structure. It was evaluated for antioxidant, cytotoxicity against human alveolar basal epithelial cell line (A-549) and human breast adenocarcinoma cell line (MCF-7) and antiviral activities; showed that the maximum antioxidant activity was 78.8 % at 3000 µg/ml after 90 min. and the IC50 value against DPPH radical found about 1500 µg/ml after 60 min. By Using MTT assay the effect of the pure compound on the proliferation of A-549 cells and MCF-7 cells were 443 µg/ml and 147.9 µg/ml, respectively. While for detection of antiviral activity using Madin-Darby canine kidney (MDCK) cells the maximum cytotoxicity was at 27.9% and IC50 was 128.1µg/ml. The maximum concentration required for protecting 50% of the virus-infected cells against H1N1 viral cytopathogenicity (EC50) was 33.25% for 80 µg/ml. This results indicated that the hydroxy marilone C has a potential antitumor and antiviral activities.

Keywords: hydroxy marilone C, production, bioactive compound, Streptomyces badius

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Authors: Samah Lakehal, A. Meliani, F. Z. Benrebiha, C. Chaouia

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In the last few years, due to the misuse of antibiotics and an increasing incidence of immunodeficiency-related diseases, the development of microbial drug resistance has become more and more of a pressing problem. Recently, natural products from medicinal plants represent a fertile ground for the development of novel antibacterial agents. Plants essential oils have come more into the focus of phytomedicine. The present study describes antimicrobial activity of Rosmarinus officinalis L. essential oil known medicinally for its powerful antibacterial properties. The essential oil of rosemary obtained by hydrodistillation (using Clevenger type apparatus) growing in Algeria (Djelfa city of south Algeria) was investigated by GC-MS. The essential oil yield of the study was 1.4 %. The major components were found to be camphor, camphene, 1,8-cineole. The essential oil has been tested for antimicrobial activity against eight bacteria (Gram-negative and Gram-positive), and three fungi including Candida albicans. Inhibition of growth was tested by the agar diffusion method based on the determination of the diameter of inhibition. The oil was found to have significant antibacterial activity and therefore can be used as a natural antimicrobial agent for the treatment of several infectious diseases caused by those germs, which have developed resistance to antibiotics.

Keywords: antimicrobial activity, Rosmarinus officinalis L., essential oils, GC/MS, camphor

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Authors: Fanjun Zhou

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In today's drug-ridden society, drug injection is gradually becoming more popular and has hidden danger to IDUs (injection drug users) such as infectious diseases. According to reports, 67% of IDUs reported improper disposal at some point over the prior 30 days, leading to a proliferation of injection needles on the streets. In recent years, the number of cases of children or ordinary people unintentionally picking up needles have increased. Various needle remover inventions have begun to surface, but the existing ones are either expensive, unportable, or risky for IDUs. In order to effectively alleviate the proliferation of drug injection needles and improve the invention of needle removers, a miniature portable needle remover and receptacle is invented. The device for capturing and storing syringe needles contains an upper lid portion mounted tightly onto the lower box portion through an interlock system on the opposing sides of the device with a breaking-twisting mechanism to remove the needle. The invention is intended to be affordable to the general public, safe enough for IDUs to use, reliable enough not to harm others, and effective in breaking needles from the syringe. This report is conducted in the hope of spreading awareness of the dangers of drug injection and to provide a way to mitigate this drug rampant situation.

Keywords: needle remover, drug injection, injection drug users, portable, receptacle

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Authors: Salem Abdalla

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Objective: Dipyrone is a widely used, well tolerated analgesic drug which, however, is compromised by agranulocytosis as an adverse effect. Subsequent to no enzymatic hydrolysis, the primary metabolic step is N-demethylation of 4-methylaminoantipyrine (4-MAA) to 4-aminoantipyrine (4-AA). The aim of the present study was to identify the cytochrome P-450 enzyme (CYP) mediating this reaction. Methods: We identified the relevant CYP using virus expressed isolated rat liver microsomes with chemical inhibition studies. The substrate of 4-methylaminantipyrine was employed at six different concentrations (25, 50, 100, 400, 800, and 1200 µmol/l) with varying concentrations of selective inhibitors of CYP1A2 (furafylline, fluvoxamine), CYP3A4 (ketoconazole), CYP2A6 (coumarin), CYP2D6 (quinidine), CYP2C19 (omeprazole, fluvoxamine, tranylcypromine), CYP2C9 (sulfaphenazole), and CYP1A1 (alpha-naphthoflavone). 4-MAA and 4-AA were analyzed by HPLC, and enzyme kinetic parameters (Km and Vmax) were determined by regression (Sigma plot 9.0). Results: The N-demethylation of 4-MAA by microsomes prepared from baculovirus-expressing human CYP was pronounced with CYP2C19. Intrinsic clearances of the most active enzymes were 0.092, 0.027, and 0.026 for the CYP enzymes 2C19, 2D6, and 1A2, respectively. Metabolism by rat liver microsomes was strongly inhibited by omeprazole (IC50 of 0.05). Conclusion: The enzyme CYP2C19 apparently has an important role in N-demethylation of 4-methylaminoantipyrine which should be further analyzed in clinical studies and which may also be interesting concerning the agranulocytosis.

Keywords: dipyrone, 4-methylaminoantipyrine (4-MAA), 4- aminoantipyrine (4-AA), metabolism, human CYP2C19

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Authors: Imeobong Joseph Inyang, Aniekan-Augusta Okon Eyo, Abel William Essien

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Hepatitis B virus (HBV) is one of the known human carcinogens. The presence of HBsAg in liver tissues indicates active viral replication. More than 85% of Hepatocellular Carcinoma (HCC) cases occur in countries with increased rates of chronic HBV infection. An evaluation study to determine the relationship between positivity for HBsAg and development of HCC and its distribution between age and gender of subjects was done. Shikata Orcein and Haematoxylin and Eosin (H&E) staining techniques were performed on liver sections. A total of 50 liver tissue specimens comprising 38 biopsy and 12 post-mortem specimens were processed. Thirty-five of the 50 specimens were positive for HBsAg with Orcein stain whereas only 16 were positive with H&E stain, and these were also positive with Orcein stain, giving an HBsAg prevalence of 70.0% (35/50). The prevalence of HCC in the study was 56.0% (28/50), of which 21 (75.0%) cases were positive for HBsAg, 18 (64.3%) were males while 10 (35.7%) were females distributed within the age range of 20-70 years. The highest number of HBsAg positive HCC cases, 7/21 (33.3%) occurred in the age group 40-49 years. There was no relationship in the pattern of distribution of HCC between age and gender using the Pearson correlation coefficient (r = 0.0474; P < 0.05). HBV infection predisposed to HCC. Orcein technique was more specific and is therefore recommended for screening of liver tissues where facilities for immunohistochemistry are inaccessible.

Keywords: Hepatitis B. surface antigen, hepatocellular carcinoma, orcein, pathology

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Authors: Seyed Hassan Moosa-kazemi, Jalal Mohammadi Soleimani, Hassan Vatandoost, Mohammad Hassan Shirazi, Sara Hajikhani, Roonak Bakhtiari, Morteza Akbari, Siamak Hydarzadeh

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Malaria is an infectious disease and considered most important health problems in the southeast of Iran. Iran is elimination malaria phase and new tool need to vector control. Paraterasgenesis is a new way to cut of life cycle of the malaria parasite. In this study, the microflora of the surface and gut of various stages of Anopheles fluviatilis James as one of the important malaria vector was studied using biochemical and molecular techniques during 2013-2014. Twelve bacteria species were found including; Providencia rettgeri, Morganella morganii, Enterobacter aerogenes, Pseudomonas oryzihabitans, Citrobacter braakii، Citrobacter freundii، Aeromonas hydrophila، Klebsiella oxytoca, Citrobacter koseri, Serratia fonticola، Enterobacter sakazakii and Yersinia pseudotuberculosis. The species of Alcaligenes faecalis, Providencia vermicola and Enterobacter hormaechei were identified in various stages of the vector and confirmed by biochemical and molecular techniques. We found Providencia rettgeri proper candidate for paratransgenesis.

Keywords: Anopheles fluviatilis, bacteria, malaria, Paraterasgenesis, Southern Iran

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Authors: Mark Osborn

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Clustered, regularly interspaced short palindromic repeat (CRISPR/Cas) proteins can be designed to bind specified DNA and RNA sequences and hold great promise for the accurate detection of nucleic acids for diagnostics. Commercially available reagents were integrated into a CRISPR/Cas9-based lateral flow assay that can detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequences with single-base specificity. This approach requires minimal equipment and represents a simplified platform for field-based deployment. A rapid, multiplex fluorescence CRISPR/Cas9 nuclease cleavage assay capable of detecting and differentiating SARS-CoV-2, influenza A and B, and respiratory syncytial virus in a single reaction was also developed. These findings provide proof of principle for CRISPR/Cas9 point-of-care diagnosis that can detect specific SARS-CoV-2 strain(s). Further, Cas9 cleavage allows for a scalable fluorescent platform for identifying respiratory viral pathogens with overlapping symptomology. Collectively, this approach is a facile platform for diagnostics with broad application to user-defined sequence interrogation and detection.

Keywords: CRISPR/Cas9, lateral flow assay, SARS-Co-V2, single-nucleotide resolution

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Authors: Amaefule, Leonard Ifeanyi

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The study evaluated the disruptions in Nigeria’s domestic economic activities occasioned by the COVID-19 pandemic: a pre and post-pandemic investigation approach. Domestic economic activities were measured with composite manufacturing purchasing managers index (PMI) and composite non-manufacturing PMI. Production and employment levels indices were proxies for composite manufacturing PMI, while business activities and employment level indices were proxies for non-manufacturing PMI. Data for these indices were sourced from monthly and quarterly publications of the Central Bank of Nigeria for periods covering fifteen (15) months before and 15 months after the outbreak of the virus in Nigeria. Test of equality of means was employed in establishing the significance of the difference of means between the pre and post-pandemic domestic economic activities. Results from the analysis indicated that a significant negative difference exists in each of the measures of domestic economic activities between the pre and post-pandemic periods. These findings, therefore, offer empirical evidence that the COVID-19 pandemic has disrupted domestic economic activities in Nigeria; thus, it exerts a negative influence on the measures of the nation’s domestic economic activities. The study thus recommended (among other things) that the Nigerian government should focus on policies that would enhance domestic production, employment and enhance business activities.

Keywords: COVID-19, domestic economic activities, composite manufacturing indices, composite non-manufacturing indices

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Authors: John Hang Leung, Shyh-Yau Wang, Hei-Tung Yip, Fion, Ho Tsung-chin, Agnes LF Chan

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Objectives: Platinum-resistant ovarian cancer has a short overall survival of 9–12 months and limited treatment options. The combination of immunotherapy and targeted therapy appears to be a promising treatment option for patients with ovarian cancer, particularly to patients with platinum-resistant recurrent ovarian cancer (PRrOC). However, there are no direct head-to-head clinical trials comparing their efficacy and toxicity. We, therefore, used a network to directly and indirectly compare seven newer immunotherapies or targeted therapies combined with chemotherapy in platinum-resistant relapsed ovarian cancer, including antibody-drug conjugates, PD-1 (Programmed death-1) and PD-L1 (Programmed death-ligand 1), PARP (Poly ADP-ribose polymerase) inhibitors, TKIs (Tyrosine kinase inhibitors), and antiangiogenic agents. Methods: We searched PubMed (Public/Publisher MEDLINE), EMBASE (Excerpta Medica Database), and the Cochrane Library electronic databases for phase II and III trials involving PRrOC patients treated with immunotherapy or targeted therapy plus chemotherapy. The quality of included trials was assessed using the GRADE method. The primary outcomes compared were progression-free survival, the secondary outcomes were overall survival and safety. Results: Seven randomized controlled trials involving a total of 2058 PRrOC patients were included in this analysis. Bevacizumab plus chemotherapy showed statistically significant differences in PFS (Progression-free survival) but not OS (Overall survival) for all interested targets and immunotherapy regimens; however, according to the heatmap analysis, bevacizumab plus chemotherapy had a statistically significant risk of ≥grade 3 SAEs (Severe adverse effects), particularly hematological severe adverse events (neutropenia, anemia, leukopenia, and thrombocytopenia). Conclusions: Bevacizumab plus chemotherapy resulted in better PFS as compared with all interested regimens for the treatment of PRrOC. However, statistical differences in SAEs as bevacizumab plus chemotherapy is associated with a greater risk for hematological SAE.

Keywords: platinum-resistant recurrent ovarian cancer, network meta-analysis, immune checkpoint inhibitors, target therapy, antiangiogenic agents

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Authors: Apoorva D. R.

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INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a severe, potentially fatal syndrome in which there is excessive immune activation. The disease is seen in children and people of all ages, but infants from birth to 18 months are most frequently affected. HLH is a sporadic or familial condition that can be triggered by various events that disturb immunological homeostasis. In cases with a genetic predisposition and sporadic occurrences, infection is a frequent trigger. Because of the rarity of this disease, the diverse clinical presentation, and the lack of specificity in the clinical and laboratory results, prompt treatment is essential, but the biggest obstacle to a favorable outcome is frequently a delay in identification. CASE REPORT: Here we report a case of a 6-month-old male infant who presented to the dermatology outpatient with disseminated skin lesions present over the face, abdomen, scalp, and bilateral upper and lower limbs for the past month. The lesions were insidious in onset, initially started over the abdomen, and gradually progressed to involve other body parts. The patient also had a history of fever which was moderate in grade, on and off in nature for 1 month. There were no significant complaints in the past, family, or drug history. There was no history of feeding difficulties in the baby. Parents gave a history of developmental milestones appropriate for age. Examination findings include multiple well-defined monomorphic erythematous papules with a central crater present over bilateral cheeks. Few lichenoid shiny papules present over bilateral arms, legs, and abdomen. Ultrasound of the abdomen and pelvis showed mild degree hepatosplenomegaly, intraabdominal lymphadenopathy, and bilateral inguinal lymphadenopathy. Routine blood investigations showed anemia and lymphopenia. Multiple X-rays of the skull, chest, and bilateral upper and lower limbs were done and were normal. Histopathology features were suggestive of non-Langerhans cell cutaneous histiocytosis. CONCLUSION: HLH is a fatal and rare disease. A high level of suspicion and an interdisciplinary approach among experienced clinicians, pathologists, and microbiologists to define the diagnosis and causative disease are key to diagnosing this case. Early detection and treatment can reduce patient morbidity and mortality.

Keywords: histiocytosis, non langerhans cell, case report, fatal, rare

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Authors: H. Moalla, A. Frikha

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Multi-criteria decision aid methods consider decision problems where numerous alternatives are evaluated on several criteria. These methods are used to deal with perfect information. However, in practice, it is obvious that this information requirement is too much strict. In fact, the imperfect data provided by more or less reliable decision makers usually affect decision results since any decision is closely linked to the quality and availability of information. In this paper, a PROMETHEE-BELIEF approach is proposed to help multi-criteria decisions based on incomplete information. This approach solves problems with incomplete decision matrix and unknown weights within PROMETHEE method. On the base of belief function theory, our approach first determines the distributions of belief masses based on PROMETHEE’s net flows and then calculates weights. Subsequently, it aggregates the distribution masses associated to each criterion using Murphy’s modified combination rule in order to infer a global belief structure. The final action ranking is obtained via pignistic probability transformation. A case study of real-world application concerning the location of a waste treatment center from healthcare activities with infectious risk in the center of Tunisia is studied to illustrate the detailed process of the BELIEF-PROMETHEE approach.

Keywords: belief function theory, incomplete information, multiple criteria analysis, PROMETHEE method

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Authors: Maha Soltan, Amal Z. Hassan, Howaida I. Abd-Alla, Atef G. Hanna

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Two naturally known cardenolides; acovenoside A and acobioside A were isolated from the Egyptian cultivar; Acokanthera spectabilis leaves. It is an ornamental and poisonous plant that has been traditionally claimed for their medicinal properties against infectious microbes, killing worms and curing some inflammations at little amounts. We examined the growth inhibition effects of both cardenolides against four types of human cancer cell lines using Sulphorhodamine B assay. In addition, the clonogenic assay was also performed for testing the growth inhibiting power of the isolated compounds. An in vitro mechanistic investigation was further accomplished against hepatocellular carcinoma HepG2 cell line. Microscopic examination, colorimetric ELISA and flow cytometry techniques were our tools of proving at least part of the anticancer pathway of the tested compounds. Both compounds were able to inhibit the growth of 4 human cancer cell lines at less than 100 nM. In addition, they were able to activate the executioner Caspase-3 and apoptosis was then induced as a consequence of cell growth arrest at G2/M. An attention must be payed to those bioactive agents particularly when giving their activity against cancer cells at considerable small values while presenting safe therapeutic margins as indicated by literature.

Keywords: anticancer, cardenolides, Caspase-3, apoptosis

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Authors: Minna Chang

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Introduction: M. pneumoniae is a respiratory pathogen, which commonly causes upper and lower respiratory infections. It primarily affects children and young adults. Respiratory symptoms are well recognized, but extrapulmonary involvement is also common. Other systems that have been implicated in the disease include: skin, mucus membranes, central, peripheral nervous systems, cardiovascular, haematological, renal, and musculoskeletal systems. Here, we report a case of an otherwise healthy, young female with M. pneumonia, who presented with right upper quadrant abdominal pain. Case presentation: a healthy 25-year-old female was referred to A&E by her general practitioner, after presenting with fever, malaise, and right upper quadrant pain. M. pneumoniae was confirmed retrospectively by serology. The patient made a full recovery after a six-day course of doxycycline 100mg. Conclusion: M. pneumonia is a well-established cause of respiratory infections in children and young adults. Febrile illness with multisystem involvement, even in the absence of respiratory symptoms, should raise suspicion of M. pneumoniae infection in healthy, young adults. Our case illustrates the multi-system involvement of M. pneumoniae, which was initially missed, due to paucity of respiratory symptoms at presentation.

Keywords: infectious diseases, mycoplasma pneumoniae, respiratory infections, extra-pulmonary manifestations

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Authors: Hakim Chayeb

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Macrophages (Mo) play an essential role in host defense against pathogens. These inflammatory cells contain a large group of inducible enzymes such as NO synthase (NOS). This study was conducted to characterize experimentally induced inflammation in vivo by lipopolysaccharides (LPS). LPS is an essential component of the outer membrane of Gram-negative bacteria and a potent inducer of macrophage. Except control rats, all rats received different doses of LPS intra-peritoneally. The involvement of inducible NO synthase (iNOS) and constitutive (cNOS ) in the modulation of the inflammatory response was studied by treating the rats with L-NAME (non-selective NOS inhibitor) or aminoguanidine (AG inhibitor of iNOS). Inhibitors were injected 24 hours before LPS administration. The results showed that esterase activity (a marker of macrophage infiltration) which is induced by LPS is reduced by AG, was potentiated by treatment with L-NAME in tissue homogenates of the liver, kidney and spleen. Meanwhile, the concentrations of nitric oxide (NO) induced by LPS were reduced with AG and are completely inhibited with L-NAME in the tissues studied. NO concentrations and plasma transaminase levels have undergone remarkable increases in rats treated with LPS alone. However, the AG significantly reduced these rates. Our results highlighted the role of NO synthase inhibitors in reducing of inflammatory responses that characterize many infectious diseases.

Keywords: aminoguanidine, esterase, LPS, L-NAME, macrophage, nitric oxide

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Authors: Stanely Nsubuga

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Background In Uganda, injection drug use is a growing but less studied problem. Preventing the transition to injection drug use may help prevent blood-borne viral transmission, but little is known about when and how people transition to injection drug use. A greater understanding of this transition process may aid in the country’s efforts to prevent the continued growth of injection drug use, HIV, and hepatitis C Virus (HCV) infection among people who inject drugs (PWID). Methods Using a rapid situation assessment framework, we conducted semi-structured interviews among 125 PWID (102 males and 23 females)—recruited through outreach and snow-ball sampling. Participants were interviewed about their experiences on when and how they transitioned into injection drug use and these issues were also discussed in 12 focus groups held with the participants. Results All the study participants started their drug use career with non-injecting forms including chewing, smoking, and sniffing before transitioning to injecting. Transitioning was generally described as a peer-driven and socially learnt behavior. The participants’ social networks and accessibility to injectable drugs on the market and among close friends influenced the time lag between first regular drug use and first injecting—which took an average of 4.5 years. By the age of 24, at least 81.6% (95.7% for females and 78.4% for males) had transitioned into injecting. Over 84.8% shared injecting equipment during their first injection, 47.2% started injecting because a close friend was already injecting, 26.4% desired to achieve a greater “high” (26.4%) which could reflect drug-tolerance, and 12% out of curiosity.

Keywords: People who Use Drugs, transition, injection drug use, Uganda

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