Search results for: innate immune mechanisms in the liver

Authors: Lena Lapidot, Amir Amnon, Rita Nosenko, Veitsman Ella, Cohen-Ezra Oranit, Davidov Yana, Segev Shlomo, Koren Omry, Safran Michal, Ben-Ari Ziv

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Introduction: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related mortality worldwide. Liver Cirrhosis is the main predisposing risk factor for the development of HCC. The factor(s) influencing disease progression from Cirrhosis to HCC remain unknown. Gut microbiota has recently emerged as a major player in different liver diseases, however its association with HCC is still a mystery. Moreover, there might be an important association between the gut microbiota, nutrition, life style and the progression of Cirrhosis and HCC. The aim of our study was to characterize the gut microbial signature in association with life style and nutrition of patients with Cirrhosis, HCC-Cirrhosis and healthy controls. Design: Stool samples were collected from 95 individuals (30 patients with HCC, 38 patients with Cirrhosis and 27 age, gender and BMI-matched healthy volunteers). All participants answered lifestyle and Food Frequency Questionnaires. 16S rRNA sequencing of fecal DNA was performed (MiSeq Illumina). Results: There was a significant decrease in alpha diversity in patients with Cirrhosis (qvalue=0.033) and in patients with HCC-Cirrhosis (qvalue=0.032) compared to healthy controls. The microbiota of patients with HCC-cirrhosis compared to patients with Cirrhosis, was characterized by a significant overrepresentation of Clostridium (pvalue=0.024) and CF231 (pvalue=0.010) and lower expression of Alphaproteobacteria (pvalue=0.039) and Verrucomicrobia (pvalue=0.036) in several taxonomic levels: Verrucomicrobiae, Verrucomicrobiales, Verrucomicrobiaceae and the genus Akkermansia (pvalue=0.039). Furthermore, we performed an analysis of predicted metabolic pathways (Kegg level 2) that resulted in a significant decrease in the diversity of metabolic pathways in patients with HCC-Cirrhosis (qvalue=0.015) compared to controls, one of which was amino acid metabolism. Furthermore, investigating the life style and nutrition habits of patients with HCC-Cirrhosis, we found significant correlations between intake of artificial sweeteners and Verrucomicrobia (qvalue=0.12), High sugar intake and Synergistetes (qvalue=0.021) and High BMI and the pathogen Campylobacter (qvalue=0.066). Furthermore, overweight in patients with HCC-Cirrhosis modified bacterial diversity (qvalue=0.023) and composition (qvalue=0.033). Conclusions: To the best of the our knowledge, we present the first report of the gut microbial composition in patients with HCC-Cirrhosis, compared with Cirrhotic patients and healthy controls. We have demonstrated in our study that there are significant differences in the gut microbiome of patients with HCC-cirrhosis compared to Cirrhotic patients and healthy controls. Our findings are even more pronounced because the significantly increased bacteria Clostridium and CF231 in HCC-Cirrhosis weren't influenced by diet and lifestyle, implying this change is due to the development of HCC. Further studies are needed to confirm these findings and assess causality.

Keywords: Cirrhosis, Hepatocellular carcinoma, life style, liver disease, microbiome, nutrition

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Authors: Rachel Shukrun, Szilvia Baron, Victoria Fidel, Anna Shusterman, Osnat Sher, Netanya Kollender, Dror Levin, Yair Peled, Yair Gortzak, Yoav Ben-Shahar, Revital Caspi, Sagi Gordon, Michal Manisterski, Ronit Elhasid

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Ewing sarcoma (EWS) is a highly aggressive cancer with a survival rate of 70–80% for patients with localized disease and under 30% for those with metastatic disease. Tumor-infiltrating neutrophils (TIN) can generate extracellular net-like DNA structures known as neutrophil extracellular traps (NETs). However, little is known about the presence and prognostic significance of tumor-infiltrating NETs in EWS. Herein, we investigated 46 patients diagnosed with EWS and treated in the Tel Aviv Medical Center between 2010 and 2021. TINs and NETs were identified in diagnostic biopsies of EWS by immunofluorescent. In addition, NETs were investigated in neutrophils isolated from peripheral blood samples of EWS patients at diagnosis and following neoadjuvant chemotherapy. The relationships between the presence of TINs and NETs, pathological and clinical features, and outcomes were analyzed. Our results demonstrate that TIN and NETs at diagnosis were higher in EWS patients with metastatic disease compared to those with local disease. High NETs formation at diagnosis predicted poor response to neo-adjuvant chemotherapy, relapse, and death from disease (P < .05). NETs formation in peripheral blood samples at diagnosis was significantly elevated among patients with EWS compared to pediatric controls and decreased significantly following neoadjuvant chemotherapy. In conclusion, NETs formation seems to have a role in the EWS immune microenvironment. Their presence can refine risk stratification, predict chemotherapy resistance and survival, and serve as a therapeutic target in patients with EWS.

Keywords: Ewing sarcoma, tumor microenvironment, neutrophil, neutrophil extracellular traps (NETs), prognosis

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Authors: Mylene T. Caytap-Milan

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This study was materialized with the purpose of determining the anxieties of students towards spoken English, sources of the specified anxiety, coping mechanisms to counter the apprehensions, and teacher management to reduce the anxiety within the classroom. Being qualitative in nature, interview as the data gathering tool was utilized with an audio-recorder. Participants of the study included thirteen teachers and students of speech classes in a state university in Region I, Philippines. Data elicited were transcribed in verbatim, confirmed by the participants, coded and categorized, and themed accordingly. A triangulation method was applied to establish the stronger validity of the data. Findings confirmed teachers’ and students’ awareness of the existence of Anxiety in speaking English (ASE). Based on the data gathered from the teachers, the following themes on students’ ASE were identified: (1) No Brain and Mouth Coordination, (2) Center of Attention, and (3) Acting Out Loud. However, the following themes were formulated based on the responses made by the students themselves: (1) The Common Feeling, (2) The Incompetent Me, and (3) The Limelight. With regard the sources of students’ ASE according to teachers are the following: (1) It Began at Home, (2) It Continued in School, (3) It’s not for me at all. On the other hand, the sources of students’ ASE according to students themselves are: (1) It Comes from Within, (2) It wasn’t Nursed Well, and (3) They’re Looking for Errors. In terms of coping with ASE, students identified the following mechanisms, which were themed into: (1) Acceptance, (2) Application, and (3) Apathy. Moreover, to reduce the ASE phenomenon within the classroom, the teachers demonstrate the following roles according to themes: (1) The Compass, (2) The Counselor, (3) The Referee, (4) The Polyglot, and (5) The English Nazi. Based on the findings, the following conclusions were drawn: (1) ASE can both serve positive and negative influences to the English speaking skills of students, (2) ASE can be reduced with teachers’ provision of more English speaking opportunities and with students’ initiative of personal training, (3) ASE can be reduced when English is introduced and practiced by children at an early age, and (4) ASE is inevitable in the affective domain thus teachers are encouraged to apply psychological positivism in the classroom. Studies related to the present undertaking may refer to the succeeding recommendations: (1) experiment on activities that will reduce anxiety ASE, (2) involve a psychologist for more critical but reliable results and recommendations, and (3) conduct the study among high school and primary students.

Keywords: coping mechanisms, sources, speaking anxiety, teacher management

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Authors: Merry Muspita Dyah Utami

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The positive effect of garlic extract have been reported by many studies. It has antibiotical potential, antibacterial, antiviral, antiparasitic, antifungal, and growth promoting. Supplementary garlic for broilers could mediate in getting the bioactive compounds in garlic. The avian bursa must be essential for antibody-mediated immunity. The size of bursa of fabricius must be some sort of endocrine or lymphoid gland associated with growth and sexual development. The research was conducted to evaluate the effects of garlic extract on growth performance and immune system of broiler. Seventy-two day old chick were equally divided into four group, three replication and six chicks each. Group I was control without garlic extract, then garlic extraxt was administrated to the experimental group II, III and IV (2, 4, 6% in ration). The experiment was conducted for three weeks period from day old chick to 21 days. Body weight of broiler were determined at day 1 and 21, feed intake was determined at the same period, feed conversion ratio was calculated accordingly. At 21 day age, four birds per replicate were slaughtered , bursa was collected, weight and calculated as a percentage of live body weight. Mortality was recorded as it occurred and was used to ajust the total number of broiler to determine the total feed intake and feed conversion rasio. Data were expressed as the mean was compare by one way analysis of variance (Anova) follow by Duncan Test, which used to identify differences between groups. A value of P<0.05 was accepted as significance. The body weight, feed conversion rasio, and the weight of bursa of fabricius showed a significant differences, but feed consumption and the percentage of bursa of live body weight were not significantly different (P > 0.05) influenced by dietary treatments. The results of this research, garlic extract has a potential role as natural growth promoter and immunomodulatory system in broiler.

Keywords: garlic extract, growth, immunity, broiler

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Authors: E. Salem

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Combustion has been used for a long time as a means of energy extraction. However, in recent years, there has been a further increase in air pollution, through pollutants such as nitrogen oxides, acid etc. In order to solve this problem, there is a need to reduce carbon and nitrogen oxides through learn burning modifying combustors and fuel dilution. A numerical investigation has been done to investigate the effectiveness of several reduced mechanisms in terms of computational time and accuracy, for the combustion of the hydrocarbons/air or diluted with hydrogen in a micro combustor. The simulations were carried out using the ANSYS Fluent 19.1. To validate the results “PREMIX and CHEMKIN” codes were used to calculate 1D premixed flame based on the temperature, composition of burned and unburned gas mixtures. Numerical calculations were carried for several hydrocarbons by changing the equivalence ratios and adding small amounts of hydrogen into the fuel blends then analyzing the flammable limit, the reduction in NOx and CO emissions, then comparing it to experimental data. By solving the conservations equations, several global reduced mechanisms (2-9-12) were obtained. These reduced mechanisms were simulated on a 2D cylindrical tube with dimensions of 40 cm in length and 2.5 cm diameter. The mesh of the model included a proper fine quad mesh, within the first 7 cm of the tube and around the walls. By developing a proper boundary layer, several simulations were performed on hydrocarbon/air blends to visualize the flame characteristics than were compared with experimental data. Once the results were within acceptable range, the geometry of the combustor was modified through changing the length, diameter, adding hydrogen by volume, and changing the equivalence ratios from lean to rich in the fuel blends, the results on flame temperature, shape, velocity and concentrations of radicals and emissions were observed. It was determined that the reduced mechanisms provided results within an acceptable range. The variation of the inlet velocity and geometry of the tube lead to an increase of the temperature and CO2 emissions, highest temperatures were obtained in lean conditions (0.5-0.9) equivalence ratio. Addition of hydrogen blends into combustor fuel blends resulted in; reduction in CO and NOx emissions, expansion of the flammable limit, under the condition of having same laminar flow, and varying equivalence ratio with hydrogen additions. The production of NO is reduced because the combustion happens in a leaner state and helps in solving environmental problems.

Keywords: combustor, equivalence-ratio, hydrogenation, premixed flames

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Authors: Ivan Zupan, Tomislav Saric, Suzana Tkalcic

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IMUNO-2865® is a commercially available, β–glucan based, natural hemicellulose compound with proven immunostimulative properties in people, domestic and some aquatic animals. During the experimental feeding trial with IMUNO-2865® in juvenile wild-caught chub under laboratory conditions, supplementation resulted in overall higher growth performance for all experimental groups regardless of the concentration of the added compound. The maximum, 5% concentration of the supplement, resulted in highest weight gain and calculated specific growth rate. In sea bream, as economically most important species in the Mediterranean aquaculture, significant increases in numbers of monocytes and heterophils were observed in the group supplemented with 2.5 % of IMUNO-2865® in the feed. An overall increase of erythrocytes was noted by the end of the experiment, although with variable distribution among groups. Blood Ca++ levels, total proteins, and total NH₃ were significantly higher after 60 days of feeding in all treatment groups compared to the control and remained elevated in the treated group following the secession of supplementation. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and serum paraoxonase PON1 (U/L) showed similar trends. All these parameters are playing a significant role in either oxygen supplementation of tissues, or anabolic and catabolic processes that on molecular levels contribute to the overall health and immune-building capacity of cells and tissues. The complete lack of mortality in sea bream and presented increases in cellular, biochemical and oxidative stress parameters in the blood suggest that the IMUNO-2865® represents a safe dietary supplement for in aquaculture, with an overall positive and potentially immunostimulative effect on farmed fish.

Keywords: IMUNO-2865®, β–glucans, Mediterranean aquaculture, fish imunnostimulans

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Authors: Tapiwa Shumba, Nyaradzo D. T. Karubwa

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Dispute resolution is the plinth of regional integration initiatives anchored on the rule of law and compliance with obligations. Without effective and reliable despite resolution mechanisms, it may be difficult to foster deeper integration. Within the Southern African Development Community (SADC) legal and institutional framework exists an apparent recognition that dispute resolution is an integral part of the regional integration. Almost all legal instruments of SADC include some provision for dispute resolution. Institutionally, the somewhat now defunct SADC Tribunal is meant to be the fulcrum for resolving disputes that arise under SADC instruments. However, after a closer analysis of the substance of these legal provisions and the attendant procedural mechanisms for addressing disputes, an argument can be made that dispute resolution in SADC is somewhat scant, fragmented and neglected. In most instruments, the common provision on dispute resolution appears to be a ‘mid-night clause’. In other instruments which have specialised provisions and procedures, questions of practicality and genius cannot be avoided. Worse still there now appears to be a lack of magnanimity between the substantive provisions in various instruments and the role of the transformed Tribunal. This scant, fragmented and neglected dispute resolution system may have an impact on the observance of the rule of law and compliance with obligations in the rules-based SADC system. This all, in turn, has an effect on the common agenda for deeper regional integration. This article seeks to expose this scant, fragmented and neglected SADC dispute resolution system and to propose a harmonised system that addresses these challenges. A ‘one stop shop’ system under a strengthened SADC tribunal is proposed as a responsive solution.

Keywords: regional integration, harmonisation, SADC tribunal, dispute resolution

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Authors: Mona T. Kashef, Omneya M. Helmy

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Multidrug resistant (MDR) bacteria have become a significant public health threat. The prevalence rates, of Gram negative MDR bacteria, are in continuous increase. However, few data are available about these resistant strains. Since, third generation cephalosporins are one of the most commonly used antimicrobials, we set out to investigate the prevalence, different mechanisms and clonal relatedness of multidrug resistance among third generation resistant Gram negative clinical isolates. A total of 114 Gram negative clinical isolates, previously characterized as being resistant to at least one of 3rd generation cephalosporins, were included in this study. Each isolate was tested, using Kirby Bauer disk diffusion method, against its assigned categories of antimicrobials. The role of efflux pump in resistance development was tested by the efflux pump inhibitor-based microplate assay using chloropromazine as an inhibitor. Detecting different aminoglycosides, β-lactams and quinolones resistance genes was done using polymerase chain reaction. The genetic diversity of MDR isolates was investigated using Random Amplification of Polymorphic DNA technique. MDR phenotype was detected in 101 isolates (89%). Efflux pump mediated resistance was detected in 49/101 isolates. Aminoglycosides resistance genes; armA and aac(6)-Ib were detected in one and 53 isolates, respectively. The aac(6)-Ib-cr allele, that also confers resistance to floroquinolones, was detected in 28/53 isolates. β-lactam resistance genes; blaTEM, blaSHV, blaCTX-M group 1 and group 9 were detected in 52, 29, 61 and 35 isolates, respectively. Quinolone resistance genes; qnrA, qnrB and qnrS were detectable in 2, 14, 8 isolates respectively, while qepA was not detectable at all. High diversity was observed among tested MDR isolates. MDR is common among 3rd generation cephalosporins resistant Gram negative bacteria, in Egypt. In most cases, resistance was caused by different mechanisms. Therefore, new treatment strategies should be implemented.

Keywords: gram negative, multidrug resistance, RAPD typing, resistance genes

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Authors: Rong Sun, Laihong Shen

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La-based perovskite oxygen carriers, especially the doped-La(M)FeO₃, showed excellent performances during chemical looping processes. However, the mechanisms of the undoped and doped La(M)FeO₃ are not clear at present, making the mechanisms clear may help the development of chemical looping technologies. In this paper, the method based on the density function theory (DFT) was used to analysis the influence of Ca, Sr, and Ba doping of La on the electronic structure, while the CO oxidation mechanisms on the surface of LaFeO₃ and Ca-doped LaFeO₃ oxygen carriers were also analyzed. The results showed that the band gap was decreased by the doping of low valence. While the doping of low valence element Ca, Sr, and Ba at La site simultaneously resulted to the moving of the valence band toward high energy and made the valence band cross the Fermi energy level. This was resulted from the holes generated by divalent ion substitution. The holes can change the total magnetization from antiferromagnet to weakly ferromagnetism. The calculation results about the formation of oxygen vacancy showed that substitutions of Ca, Sr, and Ba caused a large drop in oxygen vacancy formation energy, indicating that the bulk oxygen transport was improved. Based on the optimized bulk of the undoped and Ca-doped LaFeO₃(010) surface, the CO adsorption was analyzed. The results indicated that the adsorption energy increased by divalent ion substitution, meaning that the adsorption stability decreased. The results can provide a certain theoretical basis for the development of perovskite oxides in chemical looping technologies.

Keywords: chemical looping technologies, lanthanum ferrate (LaFeO₃), divalent ion substitution, CO oxidation

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Authors: A. Watson, G. Telford, D. I. Pritchard

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Objective: We investigated the immunomodulatory ability of licorice (Glycyrrhiza glabra). Such activities could have value for the management of common immunological diseases in dogs, such as environmental allergy. This study investigated the potential of a Licorice root extract (LRE) to influence the relative expression of Th-1, Th-2, and Th-17 cytokines in canine peripheral blood mononuclear cells (PBMC). Methods: A LRE was prepared using an alcoholic-aqueous-based solvent method. The extract was tested in three in vitro assays using canine leukocytes to determine its toxicity and immunoregulatory profile. Extract toxicity was assessed using the human T-lymphocyte cell line, Jurkat E6.1. The impact of the extract on the proliferation of concanavalin-activated canine PBMC was also determined. Finally, the extract was assessed for its ability to influence cytokine release in activated PBMC, measuring culture medium concentrations of interleukin-17, interferon gamma, and interleukin-4. One-way ANOVA followed by Dunnett’s post-test was used for statistics using concanavalin positive control as reference (p ≤ 0.05). Results: There was evidence that the LRE had specific immunomodulatory properties, causing significant inhibition of IL4 expression over a non-toxic/non-cytostatic concentration range (p < 0.001). In the same cell incubations, there was no significant impact on IL17 nor IFNg over the same non-toxic/non-cytostatic concentration range. Conclusion: The study provides in vitro evidence that LRE preferentially reduces the expression of a Th-2-type cytokine, IL4. The dog population, as with humans, is prone to conditions associated with a Th-2 bias of the immune system, such as environmental allergy. Based on these results, licorice merits further evaluation as a useful immune modulator for such allergic diseases.

Keywords: cytokine, Glycyrrhiza glabra, peripheral blood mononuclear cells, T-cell activation

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Authors: M. Abuqebitah, H. Tanyildizi, N. Yeyin, I. Cavdar, M. Demir, L. Kabasakal

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Aim: Targeted radionuclide therapy (TRT) is an increasingly used treatment modality for wide range of cancers. Presently dosimetry is highly required either to plan treatment or to ascertain the absorbed dose delivered to critical organs during treatment. Methods and Materials: The study comprised 7 patients suffered from prostate cancer with progressive disease and candidate to undergo Lu-177-DOTA-617 therapy following to PSMA- PET/CT imaging for all patients. (5.2±0.3 mCi) was intravenously injected. To evaluate bone marrow absorbed dose 2 cc blood samples were withdrawn in short variable times (3, 15, 30, 60, 180 minutes) after injection. Furthermore, whole body scans were performed using scintillation gama camera in 4, 24, 48, and 120 hours after injection and in order to quantify the activity taken up in the body, kidneys , liver, right parotid, and left parotid the geometric mean of anterior and posterior counts were determined through ROI analysis, after that background subtraction and attenuation correction were applied using patients PSMA- PET/CT images taking in a consideration: organ thickness, body thickness, and Hounsfield unites from CT scan. OLINDA/EXM dosimetry program was used for curve fitting, residence time calculation, and absorbed dose calculations. Findings: Absorbed doses of bone marrow, left kidney, right kidney, liver, left parotid, right parotid, total body were 1.28±0.52, 32.36±16.36, 32.7±13.68, 10.35±3.45, 38.67±21.29, 37.55±19.77, 2.25±0.95 (mGy/mCi), respectively. Conclusion: Our first results clarify that Lu-177-DOTA-617 is safe and reliable therapy as there were no complications seen. In the other hand, the observable variation in the absorbed dose of the critical organs among the patients necessitate patient-specific dosimetry approach to save body organs and particularly highly exposed kidneys and parotid gland.

Keywords: Lu-177-PSMA, prostate cancer, radionuclide therapy

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Authors: Mohammad K. Parvez, Mohammed S. Al-Dosari

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Hepatitis E virus (HEV) is an emerging RNA virus that causes acute and chronic liver disease with a global mortality rate of about 2%. Despite milestone developments in understanding of HEV biology, there is still lack of a robust culture system or animal model. Therefore, in a novel approach, two recombinant-baculoviruses (vBac-ORF2 and vBac-ORF3) that could overexpress HEV ORF2 (structural/capsid) and ORF3 (nonstructural/regulatory) proteins, respectively were constructed. The established HEV-SAR55 (genotype 1) replicon that contained GFP gene, in place of ORF2/ORF3 sequences was in vitro transcribed, and GFP production in RNA transfected S10-3 cells was scored by FACS. Enhanced infectivity, if any, of nascent virions produced by exogenously-supplied ORF2 and viral RNA by co-expression of ORF3 was tested on naïve HepG2 cells. Co-transduction with vBac-ORF2/vBac-ORF3 (108 pfu/microL) produced high amounts of native ORF2/ORF3 in approximately 60% of S10-3 cells, determined by immunofluorescence microscopy and Western analysis. FACS analysis showed about 9% GFP positivity of S10-3 cells on day6 post-transfection (i.e, day5 post-transduction). Further, FACS scoring indicated that lysates from S10-3 cultures receiving the RNA plus vBac-ORF2 were capable of producing HEV particles with about 4% infectivity in HepG2 cells. However, lysates of cultures co-transduced with vBac-ORF3, were found to further enhance virion infectivity by approximately 17%. This supported a previously proposed role of ORF3 as a minor-structural protein in HEV virion assembly and infectivity. In conclusion, the present model for efficient genomic RNA packaging and production of infectious virions could be a valuable tool to study various aspects of HEV molecular biology, in vitro.

Keywords: chronic liver disease, hepatitis E virus, ORF2, ORF3, replicon

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Authors: A. Paz, M. Khadka, N. Veeramisti, B. Morris

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There is a continuous large number of crashes involving pedestrians in Nevada despite the numerous safety mechanisms currently used at roadway crossings. Hence, additional as well as more effective mechanisms are required to reduce crashes in Las Vegas, in particular, and Nevada in general. A potential mechanism to reduce conflicts between pedestrians and vehicles is a High-intensity Activated crossWalK (HAWK) signal. This study evaluates the effects of such signals at a particular site in Las Vegas. Video data were collected using two cameras, facing the eastbound and westbound traffic. One week of video data before and after the deployment of the signal were collected to capture the behavior of both pedestrians and drivers. T-test analyses of pedestrian waiting time at the curb, curb-to-curb crossing time, total crossing time, jaywalking events, and near-crash events show that the HAWK system provides significant benefits.

Keywords: pedestrian crashes, HAWK signal, traffic safety, pedestrian danger index

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Authors: Constantinos S. Mammas, Andreas Lazaris, Adamantia S. Mamma-Graham, Georgia Kostopanagiotou, Chryssa Lemonidou, John Mantas, Eustratios Patsouris

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The process to build a better safety culture, methods of error analysis, and preventive measures, starts with an understanding of the effects when human factors engineering refer to remote microscopic diagnosis in surgery and specially in organ transplantation for the evaluation of the grafts. Α high percentage of solid organs arrive at the recipient hospitals and are considered as injured or improper for transplantation in the UK. Digital microscopy adds information on a microscopic level about the grafts (G) in Organ Transplant (OT), and may lead to a change in their management. Such a method will reduce the possibility that a diseased G will arrive at the recipient hospital for implantation. Aim: The aim of this study is to analyze the ergonomics of digital microscopy (DM) based on virtual slides, on telemedicine systems (TS) for tele-pathological evaluation (TPE) of the grafts (G) in organ transplantation (OT). Material and Methods: By experimental simulation, the ergonomics of DM for microscopic TPE of renal graft (RG), liver graft (LG) and pancreatic graft (PG) tissues is analyzed. In fact, this corresponded to the ergonomics of digital microscopy for TPE in OT by applying virtual slide (VS) system for graft tissue image capture, for remote diagnoses of possible microscopic inflammatory and/or neoplastic lesions. Experimentation included the development of an OTE-TS similar experimental telemedicine system (Exp.-TS) for simulating the integrated VS based microscopic TPE of RG, LG and PG Simulation of DM on TS based TPE performed by 2 specialists on a total of 238 human renal graft (RG), 172 liver graft (LG) and 108 pancreatic graft (PG) tissues digital microscopic images for inflammatory and neoplastic lesions on four electronic spaces of the four used TS. Results: Statistical analysis of specialist‘s answers about the ability to accurately diagnose the diseased RG, LG and PG tissues on the electronic space among four TS (A,B,C,D) showed that DM on TS for TPE in OT is elaborated perfectly on the ES of a desktop, followed by the ES of the applied Exp.-TS. Tablet and mobile-phone ES seem significantly risky for the application of DM in OT (p<.001). Conclusion: To make the largest reduction in errors and adverse events referring to the quality of the grafts, it will take application of human factors engineering to procurement, design, audit, and awareness-raising activities. Consequently, it will take an investment in new training, people, and other changes to management activities for DM in OT. The simulating VS based TPE with DM of RG, LG and PG tissues after retrieval, seem feasible and reliable and dependable on the size of the electronic space of the applied TS, for remote prevention of diseased grafts from being retrieved and/or sent to the recipient hospital and for post-grafting and pre-transplant planning.

Keywords: digital microscopy, organ transplantation, tele-pathology, virtual slides

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Authors: Syeda Fahria Hoque Mimmi

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Many new and promising treatments for reducing or diminishing the adverse effects of microorganisms are being discovered day by day. On the other hand, the dairy industry is accelerating the economic wheel of Bangladesh. Considering all these facts, new thoughts were developed to isolate milk proteins by the present experiment for opening up a new era of developing natural antibiotics from milk. Lactoferrin, an iron-binding glycoprotein with multifunctional properties, is crucial to strengthening the immune system and also useful for commercial applications. The protein’s iron-binding capacity makes it undoubtedly advantageous to immune system modulation and different bacterial strains. For fulfilling the purpose, 4 of raw and 17 of commercially available milk samples were collected from different farms and stores in Bangladesh (Dhaka, Chittagong, and Cox’s Bazar). Protein quantification by nanodrop technology has confirmed that raw milk samples have better quantities of protein than the commercial ones. All the samples were tested for their antimicrobial activity against 18 pathogens, where raw milk samples showed a higher percentage of antibacterial activity. In addition to this, SDS-PAGE (Sodium Dodecyl Sulfate–Polyacrylamide Gel Electrophoresis) was performed to identify lactoferrin in the milk samples. Lactoferrin was detected in 9 samples from which 4 were raw milk samples. Interestingly, Streptococcus pyogenes, Klebsiella pneumoniae, Bacillus cereus, Pseudomonas aeruginosa, Vibrio cholera, Staphylococcus aureus, and enterotoxigenic E. coli significantly displayed sensitivity against lactoferrin collected from raw milk. Only Bacillus cereus, Pseudomonas aeruginosa, Streptococcus pneumonia, Enterococcus faecalis, and ETEC (Enterotoxigenic Escherichia coli) were susceptible to lactoferrin obtained from a commercial one. This study suggested that lactoferrin might be used as the potential alternative of antibiotics for many diseases and also can be used to reduce microbial deterioration in the food and feed industry.

Keywords: alternative of antibiotics, commercially available milk, lactoferrin, nanodrop technology, pathogens, raw milk

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Authors: Adeleye Oluwagbemmiga, Obuotor Tolulope, Dosumu Adebisi, Opowoye I., Olasoju M., Kolawole Amos, Egbeyale Lawrence

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Gut Microbiota plays a vital role in animal health and welfare. This study investigated the effect of naringin and hesperidin administration on broiler birds. A total of 80 day – old broiler chicks were randomly divided into eight groups, with ten birds per group. Four groups were not inoculated but administered coccidiostat (1A), hesperidin alone (2A), naringin alone (3A) and a combination of naringin and hesperidin (4A) from day eight (8) to day fourteen (14) while four other groups (5A – 8A) were inoculated with 2 x 10⁴ oocysts per 0.5ml of Eimeria tenella on the 16th and 19th day of age after they were administered conventional antibiotics and coccidiostat, naringin (50mg/body weight), hesperidin (50mg/body weight) and a combination from day 8 - 14. McMaster counting technique was used to count the oocysts, while pour plate technique was used to determine the bacterial load. The results showed a significant increase in their performance with an average weight ranging from 1.55kg – 2.00kg, microbial load also improved with colony count values from 3.5 x 104 - 4.5 x 10⁴ CFU/ml. The study also found that the inclusion of naringin and hesperidin in the diets of broiler birds inoculated with coccidia oocysts significantly reduced the fecal oocyst counts, with the lowest count in combined treatment (8A) (10%) and indicating a lower degree of coccidiosis infection in the treated groups whereas control group (5A) had the highest oocyst count (35%). Mortality and Morbidity rate was 0% as none of the bird showed signs and symptoms. The reduction in oocyst counts could help to strengthen the immune system of broiler birds and limit the severity of coccidiosis infection, which could be an effective strategy for improving performance, immune function and mitigating the impact of coccidiosis infection in broiler birds.

Keywords: gut colonization, naringin, hesperidin, eimeria tenella, broilers

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Authors: S. Ishak, M. G. Nasuruddin

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This paper looks at healing performances as ethnographic expressions of local knowledge and culture embedded within the Malay psyche and gemeinschaft. As society develops and progresses, these healing performances are caught within conflicting trajectories which become compounded by the contestations of tradition, religious concerns, locality and modernity. As exemplifications of the Malay ethos, these performances practice common rituals, cater to the innate needs of the practitioners and serve the targeted, closed, local community. This paper traces the ethnographic methods in documenting these practices as rituals of healing in a post-modern world. It delineates the ethnographic concepts used to analyze these rituals, and to semiotically read the varied binarial oppositions and juxtapositions. The paper concludes by highlighting the reconciliatory processes involved in maintaining these ritual performances as exemplifications of the Malay ethos playing an important role in the re-aligning, re-balancing and healing of the Malay community’s psyche.

Keywords: angina, winds, semangat, spirits, traditional theatres, trance

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Authors: Haibin Zhou, Pingping Yao, Kunyang Fan

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Copper-based sintered friction materials are widely used in the brake system of different applications such as engineering machinery or high-speed train, due to the excellent mechanical, thermal and tribological performance. Considering the diversity of the working conditions of brake system, it is necessary to identify well and understand the tribological performance and wear mechanisms of friction materials for different conditions. Fe has been a preferred reinforcement for copper-based friction materials, due to its ability to improve the wear resistance and mechanical properties of material. Wear map is well accepted as a useful research method for evaluation of wear performances and wear mechanisms over a wider range of working conditions. Therefore, it is significantly important to construct a wear map which can give out the effects of work condition and Fe reinforcement on tribological performance of Cu-based friction materials. In this study, the copper-based sintered friction materials with the different addition of Fe reinforcement (0-20 vol. %) were studied. The tribological tests were performed against stainless steel in a ring-on-ring braking tester with varying braking energy density (0-5000 J/cm2). The linear wear and friction coefficient were measured. The worn surface, cross section and debris were analyzed to determine the dominant wear mechanisms for different testing conditions. On the basis of experimental results, the wear map and wear mechanism map were established, in terms of braking energy density and the addition of Fe. It was found that with low contents of Fe and low braking energy density, adhesive wear was the dominant wear mechanism of friction materials. Oxidative wear and abrasive wear mainly occurred under moderate braking energy density. In the condition of high braking energy density, with both high and low addition of Fe, delamination appeared as the main wear mechanism.

Keywords: Cu-based friction materials, Fe reinforcement, wear map, wear mechanism

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Authors: Antonio Munar-Frau, Sascha Klismoch, Manfred Schmolz, Federico Hernandez-Alfaro, Jordi Caballe-Serrano

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Introduction: Biocompatibility of biomaterials has been proposed as one of the main criteria for treatment success. For guided bone regeneration (GBR), barrier membranes present a conflict given the number of origins and modifications of these materials. The biologic response to biomaterials is orchestrated by a series of events leading to the integration or rejection of the biomaterial, posing questions such as if a longer occlusive property may trigger an inflammatory reaction. Whole blood cultures are a solution to study the immune response to drugs or biomaterials during the first 24-48 hours. The aim of this study is to determine the early immune response of different origins and chemical modifications of barrier membranes. Materials & Methods: 5 different widely used barrier membranes were included in this study: Acellular dermal matrix (AlloDerm, LifeCell®), Porcine Peritoneum (BioGide, Geistlich Pharma®), Porcine Pericardium (Jason, Botiss Biomaterials GmbH®), Porcine Cross-linked collagen (Ossix Plus, Datum Dental®) and d-PTFE (Cytoplast TXT, Osteogenics Biomedical®). Blood samples were extracted from 3 different healthy donors and incubated with the different samples of barrier membranes for 24 hours. After the incubation time, serum samples were obtained and analyzed by means of biocompatibility assays taking into account 42 markers. Results: In an early stage of the inflammatory response, the Acellular dermal matrix, porcine peritoneum and porcine cross-linked collagen expressed similar patterns of cytokine expression with a great manifestation of ENA 78. Porcine pericardium and d-PTFE presented similar cytokine activation, especially for MMP-3 and MMP-9, although other cytokines were highlighted with lower expression. For the later immune response, Porcine peritoneum and acellular dermal matrix MCP-1 and IL-15 were evident. Porcine pericardium, porcine cross-linked collagen and d-PTFE presented a high expression of IL-16 and lower manifestation of other cytokines. Different behaviors depending on an earlier or later stage of the inflammation process were observed. Barrier membrane inflammatory expression does not only differ depending on the origin, variables such as treatment of the collagen and polymers may also have a great impact on the cytokine expression of the studied barrier membranes during inflammation. Conclusions: Surface treatment and modifications might affect the biocompatibility of the membranes, as different cytokine expressions were evidently depending on the origin of the biomaterial. This study is only a brushstroke regarding the biocompatibility of materials, as it is one of the pioneer studies for ex vivo barrier membranes assays. Studies regarding surface modification are needed in order to clarify mystifications of barrier membrane science.

Keywords: biomaterials, bone regeneration, biocompatibility, inflammation

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Authors: Leila Rashki Ghaleno, Mohamad Amin Hajari, Leila Montazeri, Abdolhossein Shahverdi, Mojtaba Rezazadeh Valojerdi

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Background: Spermatogonia stem cells (SSCs) exhibit pluripotency, enabling them to undergo differentiation into many cell lineages, including neurons, glia, endothelial cells, and hepatocytes when cultured in vitro. Although the specific mechanisms are not yet fully understood, it has been observed that biopolymer agents, such as hyaluronic acid (HA) and alginate (Alg), have the potential to induce transdifferentiation of SSCs. The current work aimed to examine the process of in vitro spermatogenesis and the conversion of mouse testicular cells into hepatocytes and erythrocyte-like cells utilizing the HA-Alg hydrogel. Method: After being extracted from the testes of a 5-day postpartum mouse (5 DPP), the testicular cells were separated into two enzymatic stages and then put into a composite hydrogel containing 0.5% HA and 1% alginate. On days 14 and 28 of culture, the colonies' growth, the cells' viability, and their histology were assessed. Result: Despite observing significant cell proliferation on day 14 and the development of circular-shaped organoids on day 28, it was noted that the organoids generated in the HA-Alg medium tended to maintain their circular morphology on day 28. Notably, the testicular cells underwent transdifferentiation into cell types resembling erythrocytes and hepatocytes. The hepatocyte-like cells exhibited the presence of glycogen and lipid deposits, indicating their hepatocyte-like characteristics. Interestingly, immunostaining analysis revealed the secretion of albumin and the presence of VEGFR on day 14. However, on day 28, albumin expression was not detected, while the expression of Sox9 (a marker for hepatocytes), Vegf, CD34, and C-kit (markers for erythrocytes) showed increased levels in the gene expression evaluation. Conclusion: The present findings indicated that HA-Alg could be a potent and effective agent for the transdifferentiation of testis cells into erythrocyte and hepatocyte-like cells, as recent studies have confirmed the transformation of SSCs into hepatocyte cells during in vitro culture.

Keywords: 3D culture, mouse testicular cell, hyaluronic acid, liver organoids

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Authors: A. Satty, H. Mwambi

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Much clinical trials data-based research are characterized by the unavoidable problem of dropout as a result of missing or erroneous values. This paper aims to review some of the various techniques to address the dropout problems in longitudinal clinical trials. The fundamental concepts of the patterns and mechanisms of dropout are discussed. This study presents five general techniques for handling dropout: (1) Deletion methods; (2) Imputation-based methods; (3) Data augmentation methods; (4) Likelihood-based methods; and (5) MNAR-based methods. Under each technique, several methods that are commonly used to deal with dropout are presented, including a review of the existing literature in which we examine the effectiveness of these methods in the analysis of incomplete data. Two application examples are presented to study the potential strengths or weaknesses of some of the methods under certain dropout mechanisms as well as to assess the sensitivity of the modelling assumptions.

Keywords: incomplete longitudinal clinical trials, missing at random (MAR), imputation, weighting methods, sensitivity analysis

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Authors: Kindeye Fenta Mekonnen, Alagaw Ababu Kifle

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The failure of international responses to armed conflict to address local preconditions for national stability has recently attracted what has been called the ‘local turn’ in peace building. This ‘local turn’ in peace building amplified a renewed interest in traditional/indigenous methods of conflict resolution, a field that has been hitherto dominated by anthropologists with their focus on the procedures and rituals of such approaches. This notwithstanding, there is still limited empirical work on the relevance of traditional methods of conflict resolution to end localized conflicts vis-à-vis hybrid and modern approaches. The few exceptions to this generally draw their conclusion from very few (almost all successful) cases that make it difficult to judge the validity and cross-case application of their results. This paper seeks to fill these gaps by undertaking a quantitative analysis of the trend and applications of different communal conflict resolution initiatives, their potential to usher in long-term peace, and the extent to which their outcomes are influenced by the intensity and scope of a conflict. The paper makes the following three tentative conclusions. First, traditional mechanisms and traditional actors still dominate the communal conflict resolution landscape, either individually or in combination with other methods. Second, traditional mechanisms of conflict resolution tend to be more successful in ending a conflict and preventing its re-occurrence compared to hybrid and modern arrangements. This notwithstanding and probably due to the scholarly call for local turn in peace building, contemporary communal conflict resolution approaches are becoming less and less reliant on traditional mechanisms alone and (therefore) less effective. Third, there is yet inconclusive evidence on whether hybridization is an asset or a liability in the resolution of communal conflicts and the extent to which this might be mediated by the intensity of a conflict.

Keywords: traditional conflict resolution, hybrid conflict resolution, communal conflict, relevance, conflict intensity

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Authors: Tong-Chien Wu, Ching-Liang Hsieh, Yi-Wen Lin

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There are accumulating evidences surrounding the therapeutic effect of electroacupuncture (EA). Local EA can reliably attenuate inflammatory pain in mouse with unclear mechanisms. However, the effect of EA on distal and contralateral acupoint for pain control has been rarely studied and the result was controversial. Here in our study, we found that inflammatory hindpaw pain in mouth, which was induced by injecting the complete Freund’s adjuvant (CFA) 2 days ago can be alleviated immediately after 2Hz 15mins EA treatment at contralateral forefoot acupoint LI4 through both mechanic and thermal behavior test, while sham acupoint group is not. The efficacy was observed to be more obvious after the second round of EA treatment on the following day. This analgesic effect is produced by applying EA to a site remote from the painful area. The present study provides a powerful experimental animal model that can be used for investigating the unique physiological mechanisms involved in acupuncture analgesia.

Keywords: remote electroacupuncture, distal EA, pain control, anti-inflammation

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Authors: M. Bagheri Varzaneh, H. R. Rahmani, R. Jahanian

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The present study aimed to investigate the effects of copper-methionine on ascites incidence and hematological, morphological and enzymatic responses in broiler chickens. A total of 480 one-day-old Ross 308 broiler chicks were used in a completely randomized design in a 2×3 factorial arrangement of treatments including two ambient temperatures (thermoneutral and cold stress) and three copper levels (0, 100, and 200 mg/kg as copper-methionine) with 4 replicates (20 birds in each replicate). Broilers were kept in an environmentally-controlled room from 1 to 28 days; then, half of them exposed to cold temperature from 28 to 45 days of age. The birds were sacrificed at days 38 and 45 of age. Heparinized blood samples were collected to measure hematocrit, hemoglobin concentration, red blood cell (RBC) count, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Heart, lungs, liver, and spleen were collected and weighed separately on a sensitive digital scale. At d 38 of age, none of hematological variables, enzymatic parameters, and relative weights of organs were affected by treatments. Ascitic broilers were observed in group subjected to cold temperature and control diet (without supplemental copper) at d 45 of age. Relative weight of lungs and relative weight of heart in broilers fed on copper-methionine supplemented diets in cold temperature were lower compared with other groups. Relative liver weight, ALT, AST activities, and hematological parameters such as hematocrit, hemoglobin concentration, red blood cell count in ascitic broilers were significantly increased. In contrast, a significant decrease of the relative weight of spleen was shown in these chickens. The results showed that dietary supplementation with copper–methionine can decrease probability of ascites incidence in broilers chicks, especially under cold condition.

Keywords: ascites, cold temperature, copper-methionine, cold-stressed broiler

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Authors: Jing Li, Li Jin, Fulin Wang, Jie Dong, Wenjiang Ding

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Mg-Li dual-phase alloy exhibits better combination of yield strength and elongation than the Mg single-phase alloy. To exploit its deformation behavior, the deformation mechanisms of Mg-2Gd alloy with or without Li addition, i.e., Mg-6Li-2Gd and Mg-2Gd alloy, have been studied at both microscale and mesoscale. EBSD-assisted slip trace, twin trace, and texture evolution analysis show that the α-Mg phase of Mg-6Li-2Gd alloy exhibits different microscopic deformation mechanisms with the Mg-2Gd alloy, i.e., mainly prismatic slip in the former one, while basal slip, prismatic slip and extension twin in the latter one. Further Schmid factor analysis results attribute this different intra-phase deformation mechanisms to the higher critical resolved shear stress (CRSS) value of extension twin and lower ratio of CRSSprismatic /CRSSbasal in the α-Mg phase of Mg-6Li-2Gd alloy. Additionally, Li addition can induce dual-phase microstructure in the Mg-6Li-2Gd alloy, leading to the formation of hetero-deformation induced (HDI) stress at the mesoscale. This can be evidenced by the hysteresis loops appearing during the loading-unloading-reloading (LUR) tensile tests and the activation of multiple slip activity in the α-Mg phase neighboring β-Li phase. The Mg-6Li-2Gd alloy shows higher yield strength is due to the harder α-Mg phase arising from solid solution hardening of Li addition, as well asthe strengthening of soft β-Li phase by the HDI stress during yield stage. Since the strain hardening rate of Mg-6Li-2Gd alloy is lower than that of Mg-2Gd alloy after ~2% strain, which is partly due to the weak contribution of HDI stress, Mg-6Li-2Gd alloy shows no obvious increase of uniform elongation than the Mg-2Gd alloy.But since the β-Li phase is effective in blunting the crack tips, the Mg-6Li-2Gd alloy shows ununiform elongation, which, thus, leads to the higher total elongation than the Mg-2Gd alloy.

Keywords: Mg-Li-Gd dual-phase alloy, phase boundary, HDI stress, dislocation slip activity, mechanical properties

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Authors: Nwadioha Samuel Iheanacho, Abah Paul, Odimayo Simidele Michael

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Background: The World Health Assembly through the Global Health Sector Strategy on viral hepatitis calls for the elimination of viral hepatitis as a public health threat by 2030. All hands are on deck to actualize this goal through an effective and active vaccination and monitoring tool. Aim: To combine the Epidemiologic with Laboratory Hepatitis B Virus vaccination monitoring tools. Method: Laboratory results analysis of subjects recruited during the World Hepatitis week from July 2020 to July 2021 was done after obtaining their epidemiologic data on Hepatitis B virus risk factors, in the Medical Microbiology Laboratory of Benue State University Teaching Hospital, Nigeria. Result: A total of 500 subjects comprising males 60.0%(n=300/500) and females 40.0%(n=200/500) were recruited. A fifty-three percent majority was of the age range of 26 to 36 years. Serologic profiles were as follows, 15.0%(n=75/500) HBsAg; 7.0% (n=35/500) HBeAg; 8.0% (n=40/500) Anti-Hbe; 20.0% (n=100/500) Anti-HBc and 38.0% (n=190/500) Anti-HBs. Immune responses to vaccination were as follows, 47.0%(n=235/500) Immune naïve {no serologic marker + normal ALT}; 33%(n=165/500) Immunity by vaccination {Anti-HBs + normal ALT}; 5%(n=25/500) Immunity to previous infection {Anti-HBs, Anti-HBc, +/- Anti-HBe + normal ALT}; 8%(n=40/500) Carriers {HBsAg, Anti-HBc, Anti-HBe +normal ALT} and 7% (35/500) Anti-HBe serum- negative infections {HBsAg, HBeAg, Anti-HBc +elevated ALT}. Conclusion: The present 33.0% immunity by vaccination coverage in Central Nigeria was much lower than the 41.0% national peak in 2013, and a far cry from the global expectation of attainment of a Global Health Sector Strategy on the elimination of viral hepatitis as a public health threat by 2030. Therefore, more creative ideas and collective effort are needed to attain this goal of the World Health Assembly.

Keywords: Hepatitis B, vaccination status, laboratory tools, resource-limited settings

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Authors: Luis Gimeno, Rosmeri da Rocha, Raquel Nieto, Tercio Ambrizzi, Alex Ramos, Anita Drumond

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The transport of moisture from oceanic sources to the continents represents the atmospheric branch of the water cycle, forming the connection between evaporation from the ocean and precipitation over the continents. In this regard two large scale dynamical/meteorological structures appear to play a key role, namely Low Level Jet (LLJ) systems and Atmospheric Rivers (ARs). The former are particularly important in tropical and subtropical regions; the latter is mostly confined to extratropical regions. A key question relates to the anomalies in the transport of moisture observed during natural hazards related to extremes of precipitation (i.e., drought or wet spells). In this study we will be focused on these two major atmospheric moisture transport mechanisms (LLJs and ARs) and its role in precipitation extreme events (droughts and wet spells) in the Amazonia paying particular attention to i) intensification (decreasing) of moisture transport by them and its role in wet spells (droughts), and ii) changes in their positions and occurrence with associated flooding and wet spells.

Keywords: droughts, wet spells, amazonia, LLJs, atmospheric rivers

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Authors: Sima Parvizi Omran, Rezvan Tavakoli, Mahnaz Safari, Mohammadreza Aghasadeghi, Abolfazl Fateh, Pooneh Rahimi

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Background: SARS-CoV-2, a single-stranded RNA betacoronavirus causes the global outbreak of coronavirus disease 2019 (COVID-19). Several clinical and scientific concerns are raised by this pandemic. Genetic factors can contribute to pathogenesis and disease susceptibility. There are single nucleotide polymorphisms (SNPs) in many of the genes in the immune system that affect the expression of specific genes or functions of some proteins related to immune responses against viral infections. In this study, we analyzed the impact of polymorphism in the interferon alpha and beta receptor subunit 2 (IFNAR2) and dipeptidyl peptidase 9 (Dpp9) genes and clinical parameters on the susceptibility and resistance to Coronavirus disease (COVID-19). Methods: A total of 330- SARS-CoV-2 positive patients (188 survivors and 142 nonsurvivors) were included in this study. All single-nucleotide polymorphisms (SNPs) on IFNAR2 (rs2236757) and Dpp9 (rs2109069) were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: In survivor patients, the frequency of the favourable genotypes of IFNAR2 SNP (rs2236757 GC) was significantly higher than in nonsurvivor patients, and also Dpp9 (rs2109069 AT) genotypes were associated with the severity of COVID-19 infection. Conclusions: This study demonstrated that the severity of COVID- 19 patients was strongly associated with clinical parameters and unfavourable IFNAR2, Dpp9 SNP genotypes. In order to establish the relationship between host genetic factors and the severity of COVID-19 infection, further studies are needed in multiple parts of the world.

Keywords: SARS-CoV-2, COVID-19, interferon alpha and beta receptor subunit 2, dipeptidyl peptidase 9, single-nucleotide polymorphisms

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Authors: Nellie Nosisi Feza

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Developing young students' number sense is a priority if the aim is to build a rich mathematical foundation for successful schooling and future innovative careers. Capturing students’ interests is crucial while mediating counting concepts. This paper reports South African young children number concepts demonstrated before entering the reception class. It indicates the diverse knowledge attained in different settings before entering formal schooling. The findings indicate that their start is uneven with fully and partly attained number concepts. The findings suggest pre-schooling stimulation that provides rich mathematical experiences and purposeful play towards the attainment of core foundational concepts. Literature directs practice on important core concepts that are foundational in developing number sense.

Keywords: numeracy, learning trajectories, innate abilities, counting, Grade R/reception class

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Authors: Sina Mahdavi, Mahdi Asghari Ozma

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Multiple sclerosis (MS) is the most common inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially human Varicella-zoster virus (VZV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on VZV retrovirus infection in MS disease progression. For this study, the keywords "Multiple sclerosis", " Human Varicella-zoster virus ", and "central nervous system" in the databases PubMed, Google Scholar, Sid, and MagIran between 2016 and 2022 were searched and 14 articles were chosen, studied, and analyzed. Analysis of the amino acid sequences of HNRNPA1 with VZV proteins has shown a 62% amino acid sequence similarity between VZV gE and the PrLD/M9 epitope region (TNPO1 binding domain) of mutant HNRNPA1. A heterogeneous nuclear ribonucleoprotein (hnRNP), which is produced by HNRNPA1, is involved in the processing and transfer of mRNA and pre-mRNA. Mutant HNRNPA1 mimics gE of VZV as an antigen that leads to autoantibody production. Mutant HnRNPA1 translocates to the cytoplasm, after aggregation is presented by MHC class I, followed by CD8 + cells. Of these, antibodies and immune cells against the gE epitopes of VZV remain due to the memory immune response, causing neurodegeneration and the development of MS in genetically predisposed individuals. VZV expression during the course of MS is present in genetically predisposed individuals with HNRNPA1 mutation, suggesting a link between VZV and MS, and that this virus may play a role in the development of MS by inducing an inflammatory state. Therefore, measures to modulate VZV expression may be effective in reducing inflammatory processes in demyelinated areas of MS patients in genetically predisposed individuals.

Keywords: multiple sclerosis, varicella-zoster virus, central nervous system, autoimmunity

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