Search results for: immune modulation

Authors: Hafiz Arbab Sakandar

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Time-restricted intermittent fasting (TRIF) impacts host’s physiology and health. Plenty of health benefits have been reported for TRIF in animal models. However, limited studies have been conducted on humans especially in underdeveloped economies. Here, we designed a study to investigate the impact of TRIF/Ramadan fasting (16:8) on the modulation of gut-microbiome structure, metabolic pathways, and predicted metabolites and explored the correlation among them at different time points (during and after the month of Ramadan) in Pakistani Expats living in China. We observed different trends of Shannon-Wiener index in different subjects; however, all subjects showed substantial change in bacterial diversity with the progression of TRIF. Moreover, the changes in gut microbial structure by the end of TRIF were higher vis-a-vis in the beginning, significant difference was observed among individuals. Additionally, metabolic pathways analysis revealed that amino acid, carbohydrate and energy metabolism, glycan biosynthesis metabolism of cofactors and vitamins were significantly affected by TRIF. Pyridoxamine, glutamate, citrulline, arachidonic acid, and short chain fatty acid showed substantial difference at different time points based on the predicted metabolism. In conclusion, these results contribute to further our understanding about the key relationship among, dietary intervention (TRIF), gut microbiome structure and function. The preliminary results from study demonstrate significant potential for elucidating the mechanisms underlying gut microbiome stability and enhancing the effectiveness of microbiome-tailored interventions among the Pakistani populace. Nonetheless, extensive, and rigorous large-scale research on the Pakistani population is necessary to expound on the association between diet, gut microbiome, and overall health.

Keywords: gut microbiome, health, fasting, functionality

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Authors: Muhammad Yousaf Ali, Shahid Mansoor, Javeria Qazi, Imran Amin, Musarrat Shaheen

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Cotton leaf curl disease (CLCuD) is the major threat to the cotton crop and is transmitted by whitefly (Bemisia tabaci). Since multiple begomoviruses and associated satellites are involved in CLCuD, approaches based on the concept of broad-spectrum resistance are essential for effective disease control. Gro-El and G5 are two proteins from whitefly endosymbiont and M13 bacteriophage origin, respectively. Gro-El encapsulates the virus particle when it enters the whitefly and protects the virus from the immune system of the whitefly as well as prevents viral expression in it. This characteristic of Gro-El can be exploited to get resistance against viruses if expressed in plants. G5 is a single-stranded DNA binding protein, expression of which in transgenic plants will stop viral expression on its binding with ssDNA. The use of tissue-specific promoters is more efficient than constitutive promoters. Transgenics of Nicotiana benthamiana for Gro-El under constitutive promoter and Gro-El under phloem specific promoter were made. In comparison to non-transgenic plants, transgenic plants with Gro-El under NSP promoter showed promising results when challenged against cotton leaf curl Multan virus (CLCuMuV) along with cotton leaf curl Multan beta satellite (CLCuMB), cotton leaf curl Khokhran virus (CLCuKoV) along with cotton leaf curl Multan beta satellite (CLCuMB) and Pedilenthus leaf curl virus (PedLCV) along with Tobacco leaf curl beta satellite (TbLCB).

Keywords: cotton leaf curl disease, whitefly, endosymbionts, transgenic, resistance

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Authors: D. Avnieli

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Immunity of judges from liability represents a departure from the principle that all are equal under the law, and that victims may be granted compensation from their offenders. The purpose of the study is to determine if judicial immunity coincides with the need to ensure the existence of highly independent and incorruptible judiciary. Judges are immune from civil and criminal liability for their judicial acts. Judicial immunity is justified by the need to maintain complete independence and discretion of the judiciary. Scholars and judges believe that absolute immunity is needed to shield judges from pressures, threats, or outside interference. It is commonly accepted, that judges should be free to perform their judicial role in accordance with their assessment of the fact and their understanding of the law, without any restrictions, influences, inducements or interferences. In most countries, immunity applies when judges act in excess of jurisdiction. In some countries, it applies even when they act maliciously or corruptly. The only exception to absolute immunity applicable in all judicial systems is when judges act without jurisdiction over the subject matter. The Israeli Supreme Court recently decided to embrace absolute immunity and strike off a lawsuit of a refugee, who was unlawfully incarcerated. The Court ruled that the plaintiff cannot sue the State or the judge for damages. The questions of malice, dignity, and public scrutiny were not discussed. This paper, based on comparative analysis of many cases, aims to determine if immunity affects the dignity and behavior of judges. It demonstrates that most judges maintain their dignity and ethical code of behavior, but sometimes do not hesitate to act consciously in excess of jurisdiction, and in rare cases even corruptly. Therefore, in order to maintain independent and incorruptible judiciary, immunity should not be applied where judges act consciously in excess of jurisdiction or with malicious incentives.

Keywords: incorruptible judiciary, immunity, independent, judicial, judges, jurisdiction

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Authors: Monica M. Marcos

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In the framework of Archaeological Research, Heritage Conservation and Restoration, the object of study is metrology applied in composition of religious architecture in ancient Egypt, and usefulness in Archaology. The objective is the determination of the geometric and metrological relations in architectural models and the module used in the initial project of the buildings. The study and data collection of religious buildings, tombs and temples of the ancient Egypt, is completed with plans. The measurements systematization and buildings modulation makes possible to establish common compositional parameters, with a module determined by the measurement unit used. The measurement system corresponding to the main period of egyptian history, was the Egyptian royal cubit. The analysis of units measurements, used in architectural design, provides exact numbers on buildable spaces dimensions. It allows establishing proportional relationships between them, and finding a geometric composition module, on which the original project was based. This responds to a philosophical and functional concept of projected spaces. In the heritage rehabilitation and restoration field, knowledge of metrology helps in excavation, reconstruction and restoration of construction elements. The correct use of metrology contributes to the identification of possible work areas, helping to locate where the damaged or missing areas are. Also in restoration projects, metrology is useful for reordering and locating decontextualized parts of buildings. The conversion of measurements taken in the current International System to the ancient egyptian measurements, allows understand its conceptual purpose and its functionality, which makes easier to carry out archaeological intervention. In the work carried out in archaeological excavations, metrology is an essential tool for locating sites and establishing work zones.

Keywords: egyptology, metrology, archaeology, measurements, Egyptian cubit

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Authors: Anahit Hakobjanyan, Zdenka Navratilova, Gabriela Strakova, Martin Petrek

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Aging has a suppressive influence on human immune cells. Apoptosis may play important role in age-dependent immunosuppression and lymphopenia. Prevention of apoptosis may be promoted by BCL2-dependent and BCL2-independent manner. BCL2 is an antiapoptotic factor that has an antioxidative role by locating the glutathione at mitochondria and repressing oxidative stress. STAT3 may suppress apoptosis in BCL2-independent manner and promote cell survival blocking cytochrome-c release and reducing ROS production. The aim of our study was to estimate the influence of aging on BCL2-dependent and BCL2-independent prevention of apoptosis via measurement of BCL2 and STAT3 mRNAs expressions. The study was done on Armenian population (2 groups: 37 healthy young (mean age±SE; min/max age, male/female: 37.6±1.1; 20/54, 15/22), 28 healthy aged (66.7±1.5; 57/85, 12/16)). mRNA expression in peripheral blood leukocytes (PBL) was determined by RT-PCR using PSMB2 as the reference gene. Statistical analysis was done with Graph-Pad Prism 5; P < 0.05 considered as significant. The expression of BCL2 mRNA was lower in aged group (0.199) compared with young ones (0.643)(p < 0.01). Decrease expression was also recorded for female and male subgroups (p < 0.01). The expression level of STAT3 mRNA was increased (young, 0.228; aged, 0.428) (p < 0.05) during aging (in the whole age group and male/female subgroups). Decreased level of BCL2 mRNA may indicate about the suppression of BCL2-dependent prevention of apoptosis during aging in peripheral blood leukocytes. At the same time increased the level of STAT3 may suggest about activation of BCL2-independent prevention of apoptosis during aging.

Keywords: BCL2, STAT3, aging, apoptosis

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Authors: B. D. Ravindra, A. K. Tyagi, C. Kathirvelan

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Some micronutrients in food (milk and meat), called ‘functional food components’ exert beneficial effects other than their routine nutrient function and conjugated linoleic acid (CLA) is an unsaturated fatty acid of ruminant origin, an example of this category. However, recently the fear of hypercholesterolemia due to saturated fats has led to the avoidance of dietary fat especially of animal origin despite its advantages such as lowering blood cholesterol, immuno-modulation and anticarcinogenic property due to the presence of CLA. The dietary increase of linoleic acid (LA) and linolenic acid (LNA) is one of the feeding strategies for increasing the CLA concentration in milk. Butyrivibrio fibrisolvens is the one potential rumen bacteria, which has high potential to isomerize LA to CLA. The study was conducted to screen the different oils for CLA production, selected based on their LA concentration. Butyrivibrio fibrisolvens culture (strain 49, MZ3, 30/10) were isolated from the rumen liquor of fistulated Buffalo (age ≈ 3 years; weight ≈ 250 kg) were used in in-vitro experiments, further work was carried out with three oils viz., sunflower, mustard and soybean oil at different concentration (0.05, 0.1, 0.15, 0.2, 0.25 and 0.3 g/L of media) to study the growth of bacteria and CLA production at different incubation period (0, 8, 12, 18, 24, 48, 72 h). In the present study, growth of the bacteria was decreased linearly with increase in concentration of three oils. However, highest decrease in growth was recorded at the concentration of 0.30 g of three oils per litre of the media. Highest CLA production was 51.96, 42.08 and 25.60 µg/ml at 0.25 g and it decreased to 48.19, 39.35 and 23.41 µg/ml at 0.3 g supplementation of sunflower, soybean, and mustard oil per litre of the media, respectively at 18 h incubation period. The present study indicates the Butyrivibrio fibrisolvens bacteria involves in the biohydrogenation process, and LA rich sunflower meal can be used to improve the CLA production in rumen and thereby increasing the CLA concentration of milk.

Keywords: Butyrivibrio fibrisolvens, CLA, fatty acids, sunflower oil

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Authors: Lay Poh Tan, Chor Yong Tay, Haiyang Yu

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Micro-contact printing is a form of soft lithography that uses the relief patterns on a master polydimethylsiloxane (PDMS) stamp to form patterns of self-assembled monolayers (SAMs) of ink on the surface of a substrate through conformal contact technique. Here, we adopt this method to print proteins of different dimensions on our biodegradable polymer substrates. We started off with printing 20-500 μm scale lanes of fibronectin to engineer the shape of bone marrow derived human mesenchymal stem cell (hMSCs). After 8 hours of culture, the hMSCs adopted elongated shapes, and upon analysis of the gene expressions, genes commonly associated with myogenesis (GATA-4, MyoD1, cTnT and β-MHC) and neurogenesis (NeuroD, Nestin, GFAP, and MAP2) were up-regulated but gene expression associated to osteogenesis (ALPL, RUNX2, and SPARC) were either down modulated or remained at the nominal level. This is the first evidence that cellular morphology control via micropatterning could be used to modulate stem cell fate without external biochemical stimuli. We further our studies to modulate the focal adhesion (FA) instead of the macro shape of cells. Micro-contact printed islands of different smaller dimensions were investigated. We successfully regulated the FAs into dense FAs and elongated FAs by micropatterning. Additionally, the combined effects of hard (40.4 kPa), and intermediate (10.6 kPa) PA gel and FAs patterning on hMSCs differentiation were studied. Results showed that FA and matrix compliance plays an important role in hMSCs differentiation, and there is a cross-talk between different physical stimulants and the significance of these stimuli can only be realized if they are combined at the optimum level.

Keywords: micro-contact printing, polymer substrate, cell-material interaction, stem cell differentiation

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Authors: Sara Mohammad Atef Sabaika

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Background: The development of factor VIII (FVIII) inhibitor and hemophilic arthropathy in patients with hemophilia A (PWHA) are a great challenge for hemophilia care. Both genetic and environmental factors led to complications in PWHA. The development of inhibitory antibodies is usually induced by the immune response. Tumor necrosis factor α (TNF-α), one of the cytokines, might contribute to its polymorphism. Aim: Study the association between tumor necrosis alpha level and genotypes in pediatric patients with hemophilia A and its relation to inhibitor development and joint status. Methods: A cross-sectional study was conducted among a sufficient number of PWHA attending the Pediatric Hematology and Oncology Unit, Pediatric department in Menoufia University hospital. The clinical parameters, FVIII, FVIII inhibitor, and serum TNF-α level were assessed. The genotyping of −380G > A TNF-α gene polymorphism was performed using real time polymerase chain reaction. Results: Among the 50 PWHA, 28 (56%) were identified as severe PWHA. The FVIII inhibitor was identified in 6/28 (21.5%) of severe PWHA. There was a significant correlation between serum TNF-α level and the development of inhibitor (p = 0:043). There was significant correlation between polymorphisms of −380G > A TNF-α gene and hemophilic arthropathy development (p = 0:645). Conclusion: The prevalence of FVIII inhibitor in severe PWHA in Menoufia was 21.5%. The frequency of replacement therapy is a risk factor for inhibitor development. Serum TNF-α level and its gene polymorphism might be used to predict inhibitor development and joint status in pediatric patients with hemophilia A.

Keywords: hemophilic arthropathy, TNF alpha., patients witb hemophilia A PWHA, inhibitor

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Authors: Parvin Goli, Amirhosein Kefayat, Rezvan Goli

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Background: It is well established that parents can influence their offspring's neurodevelopment. It is shown that paternal environment and lifestyle is beneficial for the progeny's fitness and might affect their metabolic mechanisms; however, the effects of paternal exercise on the brain in the offspring have not been explored in detail. Objective: This study aims to review the impact of paternal physical exercise on memory and learning, neuroplasticity, as well as DNA methylation levels in the off-spring's hippocampus. Study design: In this systematic review and meta-analysis, an electronic literature search was conducted in databases including PubMed, Scopus, and Web of Science. Eligible studies were those with an experimental design, including an exercise intervention arm, with the assessment of any type of memory function, learning ability, or any type of brain plasticity as the outcome measures. Standardized mean difference (SMD) and 95% confidence intervals (CI) were computed as effect size. Results: The systematic review revealed the important role of environmental enrichment in the behavioral development of the next generation. Also, offspring of exercised fathers displayed higher levels of memory ability and lower level of brain-derived neurotrophic factor. A significant effect of paternal exercise on the hippocampal volume was also reported in the few available studies. Conclusion: These results suggest an intergenerational effect of paternal physical activity on cognitive benefit, which may be associated with hippocampal epigenetic programming in offspring. However, the biological mechanisms of this modulation remain to be determined.

Keywords: hippocampal plasticity, learning ability, memory, parental exercise

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Authors: Iman M. Mansour, Rania A. Zayed, Fadwa S. Abdel-Azim, Lamyaa H. Abdel-Latif

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Background and Objectives: The microenvironment of acute myeloid leukemia (AML) is suppressive for immune cells. Regulatory T cells (Tregs) have been recognized to play a role in helping leukemic cells to evade immunesurveillance. The mesenchymal stem cells (MSCs) are essential contributors in immunomodulation of the microenvironment as they can promote differentiation of Tregs via the indoleamine 2,3-dioxygenase (IDO) pathway. The aim of the present work was to evaluate the expression of IDO in bone marrow derived MSCs and to study its correlation to percentage of Tregs. Methods: 37 adult bone marrow samples were cultured in appropriate culture medium to isolate MSCs. Successful harvest of MSCs was determined by plastic adherence, morphology and positive expression of CD271 and CD105; negative expression of CD34 and CD45 using flowcytometry. MSCs were examined for IDO expression by immunocytochemistry using anti-IDO monoclonal antibody. CD4+ CD25+ cells (Tregs) were measured in bone marrow samples by flowcytometry. Results: MSCs were successfully isolated from 20 of the 37 bone marrow samples cultured. MSCs showed higher expression of IDO and Tregs percentage was higher in AML patients compared to control subjects (p=0.002 and p<0.001 respectively). A positive correlation was found between IDO expression and Tregs percentage (p value=0.012, r=0.5). Conclusion: In this study, we revealed an association between high IDO expression in MSCs and elevated levels of Tregs which has an important role in the pathogenesis of AML, providing immunosuppressive microenvironment.

Keywords: acute myeloid leukemia, indoleamine 2, 3-dioxygenase, mesenchymal stem cells, T regulatory cells

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Authors: Albina V. Moskvicheva, Gevorg G. Kazarian, Anna R. Valeeva, Marina A. Efimova, Malik N. Mukminov, Eduard A. Shuralev, Rustam Kh. Ravilov, Kamil S. Khaertynov

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Improving the early diagnosis of tuberculosis and solving a number of problems associated with the differential diagnosis of Mycobacterium bovis infection, nonspecific tuberculin reactions caused by sensitization of the body by non-tuberculosis mycobacteria, is urgent. The filtrates and extracts of M. bovis cell surface components are promising antigens with diagnostic potential. The purpose of this study was to isolate and characterize antigenic proteins and determine the dominant M. bovis antigens recognized by the humoral immune system. The mycobacterial cells were homogenized on FastPrep-24. Gel-filtration chromatography was used to fractionate the lysates of cell surface component extracts and proteins isolated from M. bovis culture supernatant. The separated fractions were analyzed using two-dimensional gel electrophoresis followed by determination of antigen serological activity using immunoblot with specific hyperimmune rabbit blood serum. As a result of electrophoretic separation of components by molecular weight, 23 antigen fractions were obtained. Analysis of densitograms showed that the fractions contained two zones of antigens with pronounced serological activity, corresponding to molecular weights of 28 and 21 kDa. The high serological activity of the 28 kDa antigen was established by immunoblot using hyperimmune blood sera. Separated and characterized by M. bovis specific antigen with a molecular weight of 28 kDa was added to the collection of specific marker antigens for M. bovis.

Keywords: antigen, gel-filtration chromatography, immunoblot, Mycobacterium bovis

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Authors: Jasna M. Čanadanović-Brunet, Gordana S. Ćetković, Jelena J. Vulić, Sonja M. Djilas, Vesna T. Tumbas Šaponjac, Sladjana M. Stajčić

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Honey serves as a source of natural antioxidants, which are effective in reducing the risk of heart disease, cancer, immune-system decline, cataracts, different inflammatory processes, and also prevent deteriorative oxidation reactions in foods such as enzymatic browning of fruit and vegetables. Honey is a natural saturated sugar solution, but it also contains certain minor constituents, proteins, enzymes, amino and organic acids, lipids, vitamins, phenolic acids, flavonoids and carotenoids. It is consumed in its natural form alone, but also in combination with nuts and various kinds of dried fruits. The aim of this research was to investigate the contribution of dried cherry on phenols (TPh) and flavonoids (Fl) contents and antioxidant activities of honey. Phenolic compounds in Serbian polyfloral (PH), linden (LH) and acacia (AH) honey and also in their mixtures with dried cherry, in 40% mass concentrations (PH40; LH40, AH40), were determined. In comparison to honey, TPh increased 2.25 times for LH40, 2.16 times for AH40 and 1.45 times for PH40, while Fl increased 2.81-fold for PH40, 1.21-fold for LH40 and 1.44-fold for AH40. Antioxidant activity was investigated with two assays, DPPH test and reducing power (RP), and expressed as EC50DPPH and RP0.5 values. The EC50DPPH values were: EC50PH40 = 1.16 mg/ml; EC50LH40= 1.42 mg/ml and EC50AH40= 1.69 mg/ml, while RP0.5 were: RP0.5PH40 = 15.05 mg/ml; RP0.5LH40 = 16.09 mg/ml and P0.5AH40 = 17.60 mg/ml. Our results indicate that supplementation of polyfloral, linden and acacia honey with 40% dried cherry improves antioxidant activity of honey by enriching the phenolic composition.

Keywords: antioxidant activity, dried cherry, honey, phenolics

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Authors: Kyungae Jo, Eun Young Kim, Byungsoo Shin, Kwang Soon Shin, Hyung Joo Suh

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Gamma-aminobutyric acid (GABA) and 5-hydroxytryptophan (5-HTP) are amino acids of digested nutrients or food ingredients and these can possibly be utilized as non-pharmacologic treatment for sleep disorder. We previously investigated the GABA/5-HTP mixture is the principal concept of sleep-promoting and activity-repressing management in nervous system of D. melanogaster. Two experiments in this study were designed to evaluate sleep-promoting effect of GABA/5-HTP mixture, to clarify the possible ratio of sleep-promoting action in the Drosophila invertebrate model system. Behavioral assays were applied to investigate distance traveled, velocity, movement, mobility, turn angle, angular velocity and meander of two amino acids and GABA/5-HTP mixture with caffeine treated flies. In addition, differentially expressed gene (DEG) analyses from next generation sequencing (NGS) were applied to investigate the signaling pathway and functional interaction network of GABA/5-HTP mixture administration. GABA/5-HTP mixture resulted in significant differences between groups related to behavior (p < 0.01) and significantly induced locomotor activity in the awake model (p < 0.05). As a result of the sequencing, the molecular function of various genes has relationship with motor activity and biological regulation. These results showed that GABA/5-HTP mixture administration significantly involved the inhibition of motor behavior. In this regard, we successfully demonstrated that using a GABA/5-HTP mixture modulates locomotor activity to a greater extent than single administration of each amino acid, and that this modulation occurs via the neuronal system, neurotransmitter release cycle and transmission across chemical synapses.

Keywords: sleep, γ-aminobutyric acid, 5-hydroxytryptophan, Drosophila melanogaster

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Authors: Debasmita Mukhopadhyay, Manika Pal Bhadra

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MiRNAs contribute to oncogenesis either as tumor suppressors or oncogenes. Hence, discovery of miRNA-based therapeutics are imperative to ameliorate cancer. Modulation of miRNA maturation is accomplished via several therapeutic agents, including small molecules and oligonucleotides. Due to the attractive pharmacokinetic properties of small molecules over oligonucleotides, we set to identify small molecule inhibitors of a metastasis-inducing microRNA. Cytotoxicity profile of aza-flavanone C1 was analyzed in a panel of breast cancer cells employing the NCI-60 screen protocols. Flow cytometry, immunofluorescence and western blotting of apoptotic or EMT markers were performed to analyze the effect of C1. A dual luciferase assay unequivocally suggested that C1 repressed endogenous miR-10b in MDA-MB-231 cells. A derivative of aza-flavanone C1 is shown as a strong inhibitor miR-10b. Blockade of miR-10b by C1 resulted in decreased expression of miR-10b targets in an aggressive breast cancer cell line model, MDA-MB-231. Abrogation of TWIST1, an EMT-inducing transcription factor also contributed to C1 mediated apoptosis. Moreover C1 exhibited a specific and selective down-regulation of miR-10b and did not function as a general inhibitor of miRNA biogenesis or other oncomiRs of breast carcinoma. Aza-flavanone congener C1 functions as a potent inhibitor of the metastasis-inducing microRNA, miR-10b. Our present study provides evidence for targeting metastasis-inducing microRNA, miR-10b with a derivative of Aza-flavanone. Better pharmacokinetic properties of small molecules place them as attractive agents compared to nucleic acids based therapies to target miRNA. Further work, in generating analogues based on aza-flavanone moieties will significantly improve the affinity of the small molecules to bind miR-10b. Finally, it is imperative to develop small molecules as novel miRNA-therapeutics in the fight against cancer.

Keywords: breast cancer, microRNA, metastasis, EMT

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Authors: Jana Tchekalarova, Milena Atanasova, Katerina Georgieva

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Melatonin deficit can cause a disturbance in emotional status and circadian rhythms of the endocrine system in the body. Both pharmacological and alternative approaches are applied for correction of dysfunctions driven by changes in circadian dynamics of many physiological indicators. In the present study, we tested and compare the beneficial effect of agomelatine (40 mg/kg, i.p. for 3 weeks) and endurance training on depressive behavior in two models of melatonin deficit in rat. The role of disturbed circadian rhythms of plasma melatonin and corticosterone secretion in the mechanism of these treatments was also explored. The continuous exercise program attenuated depressive responses associated with disrupted diurnal rhythm of home-cage motor activity, anhedonia in the sucrose preference test, and despair-like behavior in the forced swimming test were attenuated by agomelatine exposed to chronic constant light (CCL) and long-term exercise in pinealectomized rats. Parallel to the observed positive effect on the emotional status, agomelatine restored CCL-induced impairment of circadian patterns of plasma melatonin but not that of corticosterone. In opposite, exercise training diminished total plasma corticosterone levels and corrected its flattened pattern while it was unable to correct melatonin deficit in pinealectomy. These results suggest that the antidepressant-like effect of pharmacological and alternative approach might be mediated via two different mechanism, correction of the disturbed circadian rhythm of melatonin and corticosterone, respectively. Therefore, these treatment approaches might have a potential therapeutic application in different subpopulations of people characterized by a melatonin deficiency. This work was supported by the National Science Fund of Bulgaria (research grant # № DN 03/10; DN# 12/6).

Keywords: agomelatine, exercise training, melatonin deficit, corticosterone

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Authors: Emmanuel Abban Sagoe

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A proper functioning of the Central Nervous System ensures that we are able to accomplish just about everything we do as human beings such as walking, breathing, running, etc. Myelinated neurons throughout the body which transmit signals at high speeds facilitate these actions. In the case of MS, the body’s immune system attacks the myelin sheath surrounding the neurons and overtime destroys the myelin sheaths. Depending upon where the destruction occurs in the brain symptoms can vary from person to person. Fatigue is, however, the biggest problem encountered by an MS sufferer. It is very often described as the bedrock upon which other symptoms of MS such challenges in balance and coordination, dizziness, slurred speech, etc. may occur. Classifying and distinguishing between perceptions based fatigue and performance based fatigability is key to identifying appropriate treatment options for patients. Objective methods for assessing motor fatigability is also key to providing clinicians and physiotherapist with critical information on the progression of the symptom. This study tested if the Fatigue Index Kliniken Schmieder assessment tool can detect fatigability as seen in MS patients when healthy subjects with no known history of neurological pathology mimic abnormal gaits. Thirty three healthy adults between ages 18-58years volunteered as subjects for the study. The subjects, strapped with RehaWatch sensors on both feet, completed 6 gait protocols of normal and mimicked fatigable gaits for 60 seconds per each gait and at 1.38889m/s treadmill speed following clear instructions given.

Keywords: attractor attributes, fatigue index Kliniken Schmieder, gait variability, movement pattern

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Authors: Mohammadreza Aghasadeghi, Mojtaba Hamidi-Fard, Seyed Amir Sadeghi, Ashkan Noorbakhsh

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Introduction: HIV is known as one of the most important pathogens and mortality in all human societies, but unfortunately, no definitive cure has been found for it. Due to its weakened immune system, this virus causes a variety of primary and secondary opportunistic infections. Cytomegalovirus (CMV) is one of the most relevant opportunistic viruses seen in HIV-positive people that cause various infections in HIV-positive people. This virus causes various infections in HIV-positive people, such as retinal infection (CMVR), gastrointestinal infections, diarrhea, severe weight loss, and cerebrospinal fluid problems. These various infections make it important to evaluate the prevalence of CMV in HIV-positive people to diagnose it quickly and in a timely manner. This infection in HIV-positive people reduces life expectancy and causes serious harm to patients. However, a simple test in HIV-positive people can prevent the virus from progressing. Material and Methods: In this study, we collected 200 blood samples (including 147 men and 53 women) from HIV-positive individuals and examined the frequency of CMV-DNA in these cases by real-time PCR method. In the next step, the data was analyzed by SPSS software, and then we obtained the relationship between age, sex, and the frequency of CMV in HIV-positive individuals. Results: The total frequency of CMV DNA was about 59%, which is a relatively high prevalence due to the age range of the subjects. The frequency in men was 61.2% and 52.8% in women. This frequency was also higher in males than females. We also observed more frequency in two age groups of 16 to 30 years and 31 to 45 years. Discussion: Due to the high prevalence of CMV in HIV-positive individuals and causing serious problems in this group of people, this study was shown that both the patients and the community should pay more attention to this issue. Ministry of Health, as a stakeholder organization, can make CMV DNA testing mandatory as soon as a person is HIV positive.

Keywords: CMV, HIV, AIDS, real-time PCR, SPSS

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Authors: Shima Mahmoudi, Babak Pourakbari, Setareh Mamishi, Mostafa Teymuri, Majid Marjani

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Although cytokine analysis has greatly contributed to the understanding of tuberculosis (TB) pathogenesis, data on cytokine profiles that might distinguish progression from latency of TB infection are scarce. Since PE/PPE proteins are known to induce strong humoral and cellular immune responses, the aim of this study was to evaluate the diagnostic potential of interleukin-2 (IL-2) as biomarker after specific antigen stimulation with PE35 and PPE68 for the discrimination of active and latent tuberculosis infection (LTBI). The production of IL-2 was measured in the antigen-stimulated whole-blood supernatants following stimulation with recombinant PE35 and PPE68. All the patients with active TB and LTBI had positive QuantiFERON-TB Gold in Tube test. The level of IL-2 following stimulation with recombinant PE35 and PPE68 were significantly higher in LTBI group than in patients with active TB infection or control group. The discrimination performance (assessed by the area under ROC curve) for IL-2 following stimulation with recombinant PE35 and PPE68 between LTBI and patients with active TB were 0.837 (95%CI: 0.72-0.97) and 0.75 (95%CI: 0.63-0.89), respectively. Applying the 12.4 pg/mL cut-off for IL-2 induced by PE35 in the present study population resulted in sensitivity of 78%, specificity of 78%, PPV of 78% and NPV of 100%. In addition, a sensitivity of 81%, specificity of 70%, PPV of 67% and 87% of NPV was reported based on the 4.4 pg/mL cut-off for IL-2 induced by PPE68. In conclusion, peptides of the antigen PE35 and PPE68, absent from commonly used BCG strains, stimulated strong IL-2- positive T cell responses in patients with LTBI. This study confirms IL-2 induced by PE35 and PPE68 as a sensitive and specific biomarker and highlights IL-2 as new promising adjunct markers for discriminating of LTBI and Active TB infection.

Keywords: IL-2, PE35, PPE68, tuberculosis

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Authors: Emily Schlebes, Christian Hundhausen, Jens W. Fischer

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The glycosaminoglycan hyaluronan (HA) is a major component of the extracellular matrix, typically produced by fibroblasts of the connective tissue but also by immune cells. Here, we investigated the capacity of human peripheral blood CD8 T cells from healthy donors to produce HA and to express HA receptors as well as HA degrading enzymes. Further, we evaluated the effect of pharmacological HA inhibition on CD8 T cell function. Using immunocytochemistry together with quantitative PCR analysis, we found that HA synthesis is rapidly induced upon antibody-induced T cell receptor (TCR) activation and almost exclusively mediated by HA synthase 3 (HAS3). TCR activation also resulted in the upregulation of HA receptors CD44, hyaluronan-mediated motility receptor (HMMR), and layilin (LAYN), although kinetics and strength of expression varied greatly between subjects. The HA-degrading enzymes HYAL1 and HYAL2 were detected at low levels and induced by cell activation in some individuals. Interestingly, expression of HAS3, HA receptors, and hyaluronidases were modulated by the proinflammatory cytokines IL-6 and IL-1bβ in most subjects. To assess the functional role of HA in CD8 T cells, we performed carboxyfluorescein succinimidyl ester (CFSE) based proliferation assays and cytokine analysis in the presence of the HA inhibitor 4- Methylumbelliferone (4-MU). Despite significant inter-individual variation with regard to the effective dose, 4-MU resulted in the inhibition of CD8 T cell proliferation and reduced release of TNF-α and IFN-γ. Collectively, these data demonstrate that human CD8 T cells respond to TCR stimulation with a synthesis of HA and expression of HA-related genes. They further suggest that HA inhibition may be helpful in interfering with pathogenic T cell activation in human disease.

Keywords: CD8 T cells, extracellular matrix, hyaluronan, hyaluronan synthase 3

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Authors: Neda Najafi, Mehran Allalhesabi

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At present, the natural, geographical, physical contexts of the rural textures, which play a crucial role in making the concept behind their body, are not considered in the new designs. Despite the fundamental differences in contexts, this issue has caused that, the new rural textures in our country become similar to each other and the cohesive structure of many villages in the development of rural areas are exposed to deterioration. The villages of northern Iran are not immune from this situation and nothing have remained from their physical characteristic, and the new sections of rural areas are designed heterogeneously and regardless to the concepts behind the region's architecture, which destroys the originality of the environment. The purpose of this study is to extract the concepts and criteria that differentiate the body of the village and reveal its similarity with the same structures. In this way, understanding the underlying values is extremely useful and is considered very important to approach the new model. In the first part, the subject matters of the research (context, village and rural architecture) are defined and then the characteristics of context-oriented rural architecture and criteria that can be examined from the perspective of contextualism approach are presented. In the second part, by selecting 3 samples from the houses of Baliran village, these concepts and criteria have been evaluated in the houses of the village. The results of this study show that the characteristics of contextual rural architecture have the ability to adapt to the body of the village and can be the best model to achieve contextual architecture in this area. Therefore, by using these concepts and criteria, it is possible to achieve a type of architecture that is located along with the past architecture and, with the help of the modern facilities and environmental potentials, creates a logical and correct flow in the physical development of the rural textures.

Keywords: context, village, rural architecture, concepts and criteria of physical contextualism

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Authors: Yulmaida Amir, Fahrul Rozi, Insany C. Kamil, Fanny Aryani

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ODAPUS (Orang dengan Lupus) is an Indonesian term for people with Lupus, a chronic autoimmune disease in which immune system of the body becomes hyperactive and attacks normal tissue. The number of ODAPUS indicate an increase in Indonesia, thereby helping to improve their quality of life to be important to help their recovery. This study aims to examine the effect of resilience, self-esteem, and social support on the quality of life of women who had been diagnosed as having Lupus. Data were collected from 64 ODAPUS in Indonesia, using the World Health Organization Quality of Life (WHOQOL), Resilience Scale from Wagnil and Young (1993), self-esteem scale (developed from Coopersmith’s theory), and Social Support Questioner from Northouse (1988). Regression data analysis showed that resilience, social support, and self-esteem predict the quality of life of the ODAPUS simultaneously. If the variable was analysed individually, self-esteem did not significantly contribute to the quality of life. Resilience contributed most significantly to the quality of life, followed by social support. Of five sources of social supports included in the research, support from family members (parents and brother/sisters) has the most significant contribution to the quality of life, followed by support from spouse, and from friends. Interestingly, social support from medical personnel (medical doctors and nurses) had not a significant contribution to the quality of life of ODAPUS. As a conclusion, this research showed that the ability of ODAPUS to cope with difficulty in life, and support from family members, spouse, and friends were the significant predictors for their quality of life.

Keywords: quality of life, resilience, self-esteem, social supports

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Authors: Claudius Peter Van Wyk

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Given the increasingly manifest phenomena, as described in complexity theory, of volatility, uncertainty, complexity and ambiguity (VUCA), Taleb's notion of 'antifragility, has a significant contribution to make to positive psychology applied to wellbeing. Antifragility is argued to be fundamentally different from the concepts of resiliency; as the ability to recover from failure, and robustness; as the ability to resist failure. Rather it describes the capacity to reorganise in the face of stress in such a way as to cope more effectively with systemic challenges. The concept, which has been applied in disciplines ranging from physics, molecular biology, planning, engineering, and computer science, can now be considered for its application in individual human and social wellbeing. There are strong correlations to Antonovsky's model of 'salutogenesis' in which an attitude and competencies are developed of transforming burdening factors into greater resourcefulness. We demonstrate, from the perspective of neuroscience, how technology measuring nervous system coherence can be coupled to acquired psychodynamic approaches to not only identify contextual stressors, utilise biofeedback instruments for facilitating greater coherence, but apply these insights to specific life stressors that compromise well-being. Employing an on-going case study with BMW South Africa, the neurological mapping is demonstrated together with 'reframing' and emotional anchoring techniques from neurolinguistic programming. The argument is contextualised in the discipline of psychoneuroimmunology which describes the stress pathways from the CNS and endocrine systems and their impact on immune function and the capacity to restore homeostasis.

Keywords: antifragility, complexity, neuroscience, psychoneuroimmunology, salutogenesis, volatility

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Authors: Xing Yan Fan, Xing Lin Xu, Man Yuan Chen, Pei Tzu Lee, Yu Ting Wang, Yi Xiao Cao, Rui Yao

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Pyramid sales have been a widespread issue in China. Victims who are defrauded not only lose money but damage interpersonal relationship. A deeper understanding of pyramid-sale models can be beneficial to prevent potential victims from fraud and improve the property security. The goals of this study were to detect psychological characteristics of pyramid-sale sellers, and analyse persuasive skills in pyramid organizations. A qualitative study was conducted in this study. Participants (n=6) recruited by 'snowball' sampling from present pyramid-sale sellers (n=3) and imprisoned pyramid-sale sellers (n=3). All participants accepted semi-structured interview for collecting data. Content analysis was adopted for data coding and analysis. The results indicate that pyramid organizations are used to utilize their appearance packaging and celebrity effect to strengthen the positions in participants’ mind. The status gap between pyramid-sale sellers in same organization, as well as rewards to increase reputation, are used to motivate participants in pyramid. The most significant common characteristics among all participants are that they tend to possess a high sense of belongingness within the firm. Moreover, the expression of pyramid-sale sellers on gambling mentality is expected to growth as constantly losing money. Findings suggest that the psychological characteristics of pyramid-sale sellers in accordance with Maslow’s hierarchy of needs, persuasive skills of pyramid organization confront to 'attitude-behaviour change model'. These findings have implication on 'immune education' that providing guidance for victims out of stuck and protecting ordinary people from the jeopardizing of pyramid sales.

Keywords: pyramid sales, characteristics, persuasive skills, qualitative study

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Authors: Jitaree Tantiyasawatdikul, Bantita Jadnok, Sarunya Tijana

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Background: Nutritional status is an important factor before, during, and after an operation. It can help wound healing. If the patients have good nutritional status before and after an operation, wound healing can occur more easily. It can strengthen the immune system leading to decreased infection, reduced length of stay, and reducing the cost to patients and caregivers. Therefore, screening to evaluate the nutritional status of patients in 3B becomes the database for further developing the treatment and also will lead to excellent service from the interdisciplinary team. Objective: To study the nutritional status of patients in surgical ward 3B at Surgical and Orthopedics Nursing Division, Srinagarind Hospital. Method: A descriptive study, to evaluate the nutritional status of 86 patients admitted in 3B between October 2014 and March 2015.The instruments used in this study consisted of two parts: 1) personal data, 2) Screening nutritional status. The data were analyzed by percentage and mean. Results: A sample population of 86 patients aged 22-81 years old, mean age 52.59years, 90.69% are married, female were 55.81%, regular diet 70.93%, patients with no problem oral cavity was 87.21%.The sample population had high incidence of CA 47.67% and secondly cardiovascular disease 36.05 %. Patients with high-risk nutrition was 12.79 % including 45.45% cardiovascular disease and 36.36% CA. Screening of nutritional status of high-risk nutrition was 39.36% severe triceps skinfold (TSF), severe mid-arm muscle circumference(MAMC) 9.09% and severe total lymphocyte 39.36%. Conclusion: The result of nutritional status screening of surgical ward 3B found 12.79% patients with high-risk nutrition including 45.45% with cardiovascular disease .There was no problem with oral cavity and eating.

Keywords: nutritional status, screening, surgical patients, 3B ward, Srinagarind Hospital

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Authors: Nick Weir, Robert Stevens, Alan Hargreaves, Martin McGinnity, Chris Tinsley

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Hydrophobic materials have previously demonstrated the ability to elevate cell-cell interactions and promote the formation of neural networks whilst aligned nanofibers demonstrate the ability to induce extensive neurite outgrowth in an aligned manner. Hydrophobic materials typically elicit an immune response upon implantation and thus materials used for implantation are typically hydrophilic. Poly-L-lactic acid (PLLA) is a hydrophobic, non-immunogenic, FDA approved material that can be electrospun to form aligned nanofibers. Primary rat cortical neurons cultured for 10 days on aligned PLLA nanofibers formed 3D cell clusters, approximately 800 microns in diameter. Neurites that extended from these clusters were highly aligned due to the alignment of the nanofibers they were cultured upon and fasciculation was also evident. Plasma treatment of the PLLA nanofibers prior to seeding of cells significantly reduced the hydrophobicity and abolished the cluster formation and neurite fasciculation, whilst reducing the extent and directionality of neurite outgrowth; it is proposed that hydrophobicity induces the changes to cellular behaviors. Aligned PLLA nanofibers induced the formation of a structure that mimics the grey-white matter compartmentalization that is observed in vivo and thus represents a step forward in generating organoids or biomaterial-based implants. Upon implantation into the brain, the biomaterial architectures described here may provide a useful platform for both brain repair and brain remodeling initiatives.

Keywords: hydrophobicity, nanofibers, neurite fasciculation, neurite outgrowth, PLLA

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Authors: Debatosh Das, Moxian Chen, Jianhua Zhang, Caroline Gutjahr

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Arbuscular mycorrhiza (AM) is a mutualistic symbiosis between plant roots and Glomeromycotina fungi, which is activated under low but inhibited by high phosphate. The effect of phosphate on AM development has been observed for many years, but mechanisms regulating it under contrasting phosphate levels remain unknown. Based on previous observations that promoters of several AM functional genes contain PHR binding motifs, we hypothesized that PHR2, a master regulator of phosphate starvation response in rice, was recruited to regulate AM symbiosis development. We observed a drastic reduction in root colonization and significant AM transcriptome modulation in phr2. PHR2 targets genes required for root colonization and AM signaling. The role of PHR2 in improving root colonization, mycorrhizal phosphate uptake, and growth response was confirmed in field soil. In conclusion, rice PHR2, which is considered a master regulator of phosphate starvation responses, acts as a positive regulator of AM symbiosis between Glomeromycotina fungi and rice roots. PHR2 directly targets the transcription of plant strigolactone and AM genes involved in the establishment of this symbiosis. Our work facilitates an understanding of ways to enhance AMF propagule populations introduced in field soils (as a biofertilizer) in order to restore the natural plant-AMF networks disrupted by modern agricultural practices. We show that PHR2 is required for AM-mediated improvement of rice yield in low phosphate paddy field soil. Thus, our work contributes knowledge for rational application of AM in sustainable agriculture. Our data provide important insights into the regulation of AM by the plant phosphate status, which has a broad significance in agriculture and terrestrial ecosystems.

Keywords: biofertilizer, phosphate, mycorrhiza, rice, sustainable, symbiosis

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Authors: Moussa Majed, Omar Yaser

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The main objective of this experiment was to study the impact of Probiotic compound on the specific immunity as the case study of infectious bursal disease. Total of 8000 one-day old Ross 108 broiler were randomly divided into two experimental groups; control group (4500 birds) and experimental group (3500 birds). Birds in two groups were reared under similar environmental conditions. Birds in control group received basal diets without probiotic whereas the birds in experimental one were fed basal diets supplemented with a commercial probiotic mixture) probiotic lacting k, which contains bacteria cells beyond to lactobacillus, Streptococcus and bifidobacterium genus that are isolated from gut microflora in healthy chickens(. The commercial probiotic were used according to the manufacturer instruction. 400 blood samples for each group were collected from wing vein every 5-7 days as interval period till 42 days old. Indirect Enzyme-Linked Immunosorbent Assay (ELISA) test was performed to detect the level of infectious bursal disease virus (IBDV) antibodies. The results clearly showed that the mean of immune titers was significantly (p= 0.03) higher in trail group than control one. The coefficient of variance percentages were 55% and 39% for control and trial groups respectively, this illustrates that homogeneity of immunity titers in the trail group was much better comparing with control group. The values of geometric means of titers in the control group and trial group were reported 3820 and 8133, respectively. The crude mortality rate in the experimental group was two times lower comparing with control group (14% and 28% respectively, p = 0.005

Keywords: probiotic, broiler chicken, infectious bursal disease, immunity, ELISA test

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Authors: Kevin Yeo, Christine Hall, Babinchak Tim

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BAT® [Botulism Antitoxin Heptavalent (A,B,C,D,E,F,G)-(Equine)] anti-toxin is a mixture of equine immune globulin fragments indicated for the treatment of symptomatic botulism in adult and pediatric patients. The effectiveness of BAT anti-toxin is based on efficacy studies conducted in animal models. A general explanation of the pivotal animal studies, post market surveillance and outcomes of an observational patient registry for patients treated with BAT product distributed in the USA is briefly discussed. Overall it took 20 animal studies for two well-designed and appropriately powered pivotal efficacy studies – one in which the effectiveness of BAT was assessed against all 7 serotypes in the guinea pig, and the other where efficacy is confirmed in the Rhesus macaque using Serotype A. Clinical Experience for BAT to date involves approximately 600 adult and pediatric patients with suspected botulism. In pre-licensure, patient data was recorded under the US CDC expanded access program (259 adult and pediatric patients between 10 days to 88 years of age). In post licensure, greater than 350 patients to date have received BAT and been followed up by enhanced expanded access program. The analysis of the post market surveillance data provided a unique opportunity to demonstrate clinical benefit in the field study required by the animal rule. While the animal rule is applied because human efficacy studies are not ethical or feasible, a post-marketing requirement is to conduct a study to evaluate safety and clinical benefit when circumstances arise and demonstrate the favourable benefit-risk profile that supported licensure.

Keywords: botulism, threat, clinical benefit, observational patient registry

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Authors: Rotondwa P. Gunununu, Mustapha Mohammed, Felix D. Dakora

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Common bean is the most importantly high protein grain legume grown in Southern Africa for human consumption and income generation. Although common bean can associate with rhizobia to fix N₂ for bacterial use and plant growth, it is reported to be a poor nitrogen fixer when compared to other legumes. N₂ fixation can vary with legume species, genotype and rhizobial strain. Therefore, screening legume germplasm can reveal rhizobia/genotype combinations with high N₂-fixing efficiency for use by farmers. This study assessed symbiotic performance and N₂ fixation in 63 common bean genotypes under field conditions at Malkerns Station in Eswatini, using the ¹⁵N natural abundance technique. The shoots of common bean genotypes were sampled at a pod-filling stage, oven-dried (65oC for 72h), weighed, ground into a fine powder (0.50 mm sieve), and subjected to ¹⁵N/¹⁴N isotopic analysis using mass spectrometry. At maturity, plants from the inner rows were harvested for the determination of grain yield. The results revealed significantly higher modulation (p≤0.05) in genotypes MCA98 and CIM-RM01-97-8 relative to the other genotypes. Shoot N concentration was highest in genotype MCA 98, followed by KAB 10 F2.8-84, with most genotypes showing shoot N concentrations below 2%. Percent N derived from atmospheric N₂ fixation (%Ndfa) differed markedly among genotypes, with CIM-RM01-92-3 and DAB 174, respectively, recording the highest values of 66.65% and 66.22 % N derived from fixation. There were also significant differences in grain yield, with CIM-RM02-79-1 producing the highest yield (3618.75 kg/ha). These results represent an important contribution in the profiling of symbiotic functioning of common bean germplasm for improved N₂ fixation.

Keywords: nitrogen fixation, %Ndfa, ¹⁵N natural abundance, grain yield

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Authors: Yahya Almurtadha, Mukhtar Ghaleb, Ahmed M. Shamsan Saleh

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The world witnessed a fierce attack from the Covid-19 virus, which affected public life socially, economically, healthily and psychologically. The world's governments tried to confront the pandemic by imposing a number of precautionary measures such as general closure, curfews and social distancing. Scientists have also made strenuous efforts to develop an effective vaccine to train the immune system to develop antibodies to combat the virus, thus reducing its symptoms and limiting its spread. Artificial intelligence, along with researchers and medical authorities, has accelerated the vaccine development process through big data processing and simulation. On the other hand, one of the most important negatives of the impact of Covid 19 was the state of anxiety and fear due to the blowout of rumors through social media, which prompted governments to try to reassure the public with the available means. This study aims to proposed using Sentiment Analysis (AKA Opinion Mining) and deep learning as efficient artificial intelligence techniques to work on retrieving the tweets of the public from Twitter and then analyze it automatically to extract their opinions, expression and feelings, negatively or positively, about the symptoms they may feel after vaccination. Sentiment analysis is characterized by its ability to access what the public post in social media within a record time and at a lower cost than traditional means such as questionnaires and interviews, not to mention the accuracy of the information as it comes from what the public expresses voluntarily.

Keywords: deep learning, opinion mining, natural language processing, sentiment analysis

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