Search results for: dengue virus infection
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1843

Search results for: dengue virus infection

1723 Role of Interleukin-36 in Response to Pseudomonas aeruginosa Infection

Authors: Muslim Idan Mohsin, Mohammed Jasim Al-Shamarti, Rusul Idan Mohsin, Ali A. Majeed

Abstract:

One of the causative agents of the lower respiratory tract (LRT) is Pseudomonas aeruginosa, which can lead to severe infection associated with a lung infection. There are many cytokines that are secreted in response to bacterial infection, in particular interleukin IL-36 cytokine in response to P. aeruginosa infection. The involvement of IL-36 in the P. aeruginosa infection could be a clue to find a specific way for treatments of different inflammatory and degenerative lung diseases. IL36 promotes primary immune response via binding to the IL-36 receptor (IL-36R). Indeed, an overactivity of IL-36 might be an initiating factor for many immunopathologic sceneries in pneumonia. Here we demonstrate if the IL-36 cytokine increases in response P. aeruginosa infection that is isolated from lower respiratory tract infection (LRT). We demonstrated that IL-36 expression significantly unregulated in human lung epithelial (A549) cells after infected by P. aeruginosa at mRNA level.

Keywords: IL36, Pseudomonas aeruginosa, LRT infection, A549 cells

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1722 Serological Assay and Genotyping of Hepatitis C Virus in Infected Patients in Zanjan Province

Authors: Abdolreza Esmaeilzadeh, Maryam Erfanmanesh, Sousan Ghasemi, Farzaneh Mohammadi

Abstract:

Background: Hepatitis C Virus (HCV), a public health problem, is an enveloped, single-stranded RNA virus and a member of the Hepacivirus genus of the Flaviviridae family. Liver cancer, cirrhosis, and end-stage liver are the outcomes of chronic infection with HCV. HCV isolates show significant heterogeneity in genetics around the world. Therefore, determining HCV genotypes is a vital step in determining prognosis and planning therapeutic strategies. Materials and Methods: Serum samples of 136 patients were collected and analyzed for anti-HCV antibodies using ELISA (The enzyme-linked immunosorbent assay) method. Then, positive samples were exposed to RT-PCR, which was performed under standard condition. Afterwards, they investigated for genotyping using allele-specific PCR (AS-PCR), and HCV genotype 2.0 line probe assay (LiPA). Results: Samples indicated 216 bp bands on 2% agarose gel. Analyses of the results demonstrated that the most dominant subtype was 3a with frequency of 38.26% in Zanjan Province followed by subtypes of 1b, 1a, 2, and 4 with frequencies of 25.73%, 22.05%, 5.14%, and 4.41%, respectively. The frequency of unknown HCV genotypes was 4.41%. Conclusions: According to the results, it was found that HCV high prevalent genotype in Zanjan is subtype 3a. Analysis of the results provides identification of certain HCV genotypes, and these valuable findings could affect the type and duration of the treatment.

Keywords: anti-HCV antibody, Hepatitis C Virus (HCV), genotype, RT-PCR, AS-PCR

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1721 A Description Analysis of Mortality Rate of Human Infection with Avian Influenza A(H7N9) Virus in China

Authors: Lei Zhou, Chao Li, Ruiqi Ren, Dan Li, Yali Wang, Daxin Ni, Zijian Feng, Qun Li

Abstract:

Background: Since the first human infection with avian influenza A(H7N9) case was reported in China on 31 March 2013, five epidemics have been observed in China through February 2013 and September 2017. Though the overall mortality rate of H7N9 has remained as high as around 40% throughout the five epidemics, the specific mortality rate in Mainland China varied by provinces. We conducted a descriptive analysis of mortality rates of H7N9 cases to explore the various severity features of the disease and then to provide clues of further analyses of potential factors associated with the severity of the disease. Methods: The data for analysis originated from the National Notifiable Infectious Disease Report and Surveillance System (NNIDRSS). The surveillance system and identification procedure for H7N9 infection have not changed in China since 2013. The definition of a confirmed H7N9 case is as same as previous reports. Mortality rates of H7N9 cases are described and compared by time and location of reporting, age and sex, and genetic features of H7N9 virus strains. Results: The overall mortality rate, the male and female specific overall rates of H7N9 is 39.6% (608/1533), 40.3% (432/1072) and 38.2% (176/461), respectively. There was no significant difference between the mortality rates of male and female. The age-specific mortality rates are significantly varied by age groups (χ²=38.16, p < 0.001). The mortality of H7N9 cases in the age group between 20 and 60 (33.17%) and age group of over 60 (51.16%) is much higher than that in the age group of under 20 (5.00%). Considering the time of reporting, the mortality rates of cases which were reported in the first (40.57%) and fourth (42.51%) quarters of each year are significantly higher than the mortality of cases which were reported in the second (36.02%) and third (27.27%) quarters (χ²=75.18, p < 0.001). The geographic specific mortality rates vary too. The mortality rates of H7N9 cases reported from the Northeast China (66.67%) and Westeast China (56.52%) are significantly higher than that of H7N9 cases reported from the remained area of mainland China. The mortality rate of H7N9 cases reported from the Central China is the lowest (34.38%). The mortality rates of H7N9 cases reported from rural (37.76%) and urban (38.96%) areas are similar. The mortality rate of H7N9 cases infected with the highly pathogenic avian influenza A(H7N9) virus (48.15%) is higher than the rate of H7N9 cases infected with the low pathogenic avian influenza A(H7N9) virus (37.57%), but the difference is not statistically significant. Preliminary analyses showed that age and some clinical complications such as respiratory failure, heart failure, and septic shock could be potential risk factors associated with the death of H7N9 cases. Conclusions: The mortality rates of H7N9 cases varied by age, sex, time of reporting and geographical location in mainland China. Further in-depth analyses and field investigations of the factors associated with the severity of H7N9 cases need to be considered.

Keywords: H7N9 virus, Avian Influenza, mortality, China

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1720 Double-Spear 1-H2-1 Oncolytic-Immunotherapy for Refractory and Relapsing High-Risk Human Neuroblastoma and Glioma

Authors: Lian Zeng

Abstract:

Double-Spear 1-H2-1 (DS1-H2-1) is an oncolytic virus and an innovative biological drug candidate. The chemical composition of the drug product is a live attenuated West Nile virus (WNV) containing the human T cell costimulator (CD86) gene. After intratumoral injection, the virus can rapidly self-replicate in the injected site and lyse/kill the tumor by repeated infection among tumor cells. We also established xenograft tumor models in mice to evaluate the drug candidate's efficacy on those tumors. The results from preclinical studies on transplanted tumors in immunodeficient mice showed that DS1-H2-1 had significant oncolytic effects on human-origin cancers: it completely (100%) shrieked human glioma; limited human neuroblastoma growth reached as high as 95% growth inhibition rate (%TGITW). The safety data of preclinical animal experiments confirmed that DS1-H2-1 is safe as a biological drug for clinical use. In the preclinical drug efficacy experiment, virus-drug administration with different doses did not show abnormal signs and disease symptoms in more than 300 tested mice, and no side effects or death occurred through various administration routes. Intravenous administration did not cause acute infectious disease or other side effects. However, the replication capacity of the virus in tumor tissue via intravenous administration is only 1% of that of direct intratumoral administration. The direct intratumoral administration of DS1-H2-1 had a higher rate of viral replication. Therefore, choosing direct intratumoral injection can ensure both efficacy and safety.

Keywords: oncolytic virus, WNV-CD86, immunotherapy drugs, glioma, neuroblastoma

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1719 Prevalence of Cytomegalovirus DNA in the Patients’ Serum with HIV using Real-Time PCR

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

Abstract:

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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1718 Assessment of HIV/Hepatitis B Virus Co-Infection among Patients Living with HIV in Northern and Southern Region of Nigeria

Authors: Folajinmi Oluwasina, Greg Abiaziem, Moses Luke, Mobolaji Kolawole, Nancy Yibowei, Anne Taiwo

Abstract:

Background: Occurrence of HIV infection has an adverse effect on the natural causes of Hepatitis B Viral (HBV) infection, faster progression of hepatic fibrosis demonstrated in patients with co-infection. This study was carried out to determine the incidence of HBV infection among HIV-positive patients, and to retrospectively evaluate laboratory characteristics of patients with HIV/HBV co-infection. Methods: A retrospective analysis of patient files for all HIV-infected cases followed-up and treated at 52 health facilities. Among HIV-infected cases, those with HBsAg positivity and HIV/Hepatitis B co-infection were determined. Socio demographic, alcohol or substance use, ART, CD4, Viral Load levels and treatment durations were retrospectively evaluated. Results: Of the 125 HIV-infected patients evaluated retrospectively, 17 (13.6%) had HBsAg positivity. Of these 17 cases were 11(64.7%) male and 6 (35.3%) female, with a mean age of 48.7 years. No patients had a history of alcohol or substance use. The mean duration of follow up was 28 months. 9 (52.9%) patients had negative HBV DNA at presentation while 8(47%) had positive HBV DNA, with normal ALT levels in all subjects. Among the 9 cases with negative HBV DNA who had no indication for the treatment of chronic hepatitis B. In five cases, treatment was commenced since HBV DNA was elevated in conjunction with low CD4. One patient in whom treatment was not indicated based on HBV DNA and CD4 levels in conjunction with the absence of AIDS defining clinical picture was currently being followed-up without treatment. Of the patients receiving HAART therapy, the average CD4 count at presentation was 278 cells/mm3 vs. 466 cells/mm3 at the end of 12 months. In three subjects with positive HBV DNA, a decrease in HBV DNA was noted after initiation of treatment. In four patients with negative DNA who received treatment, the HBV DNA negative status was found to remain, while one patient who did not receive treatment had elevated HBV DNA and decreased CD4 levels. Conclusion: It was shown that this group of patients with HIV/HBV co-infection, HAART was found to be associated with a decrease in HBV DNA in HBV DNA positive cases, absence of transition to positivity among those with negative HBV DNA, and with increased CD4 in all subjects.

Keywords: Hepatitis B, DNA, anti retroviral therapy, co-infection

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1717 Public Perception and Willingness to Undergo Cosmetic Procedures during COVID-19 Pandemic: A Questionnaire-Based Study Applied to Asymptomatic Individuals

Authors: Ibrahim Alreshidi, Aseel Albrekeit, Ruaa Alharthi

Abstract:

Background: As a result of the spread of COVID-19 at the beginning of 2020, many governments, including Saudi Arabia, have suspended operations in many agencies. Most dermatologists have restricted their practice, including cosmetic procedures, to ensure social distancing. On the 7th of May 2020, Saudi authorities reduced the restriction of COVID-19 virus preventative measures, allowing clinics to start accepting patients following the ministry of health protocols. Objectives: Evaluation of the public's perception and willingness to undergo cosmetic procedures during COVID-19 outbreaks in Saudi Arabia. Materials and methods: A descriptive, cross-sectional, questionnaire-based study was carried out among the individuals who lack typical symptoms of COVID-19 infection in Saudi Arabia. A self-designed web-based questionnaire was developed; content face validity and a pilot study were done. The questionnaire was distributed electronically from the 8th of May until the 31st of May 2020. Results: A total of 656 individuals who lack typical symptoms of COVID-19 infection were included in this analysis. Only 10.5% of participants expressed their will to do cosmetic procedures during the COVID-19 pandemic. More than 90% of the participants believed that the COVID-19 pandemic was either somewhat serious (52.9%) or very serious (38.7%). The willingness to do cosmetic procedures during the COVID-19 pandemic remained unaltered when the price was discounted (p<0.001) and when infection control measures were ensured (p<0.001). Conclusion: The COVID-19 pandemic had a negative impact on the practice of cosmetic dermatology. Fear of transferring the infection to a beloved home member is the main reason to avoid these procedures. Generating well-structured safety guidelines to decrease the risk of this unusual virus transmission in dermatology practice and creating financial incentives may help increase the public willingness to do these cosmetic procedures during this pandemic.

Keywords: COVID-19 pandemic, cosmetic procedures, questionnaire, dermatology

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1716 Zika Virus NS5 Protein Potential Inhibitors: An Enhanced in silico Approach in Drug Discovery

Authors: Pritika Ramharack, Mahmoud E. S. Soliman

Abstract:

The re-emerging Zika virus is an arthropod-borne virus that has been described to have explosive potential as a worldwide pandemic. The initial transmission of the virus was through a mosquito vector, however, evolving modes of transmission has allowed the spread of the disease over continents. The virus already been linked to irreversible chronic central nervous system (CNS) conditions. The concerns of the scientific and clinical community are the consequences of Zika viral mutations, thus suggesting the urgent need for viral inhibitors. There have been large strides in vaccine development against the virus but there are still no FDA-approved drugs available. Rapid rational drug design and discovery research is fundamental in the production of potent inhibitors against the virus that will not just mask the virus, but destroy it completely. In silico drug design allows for this prompt screening of potential leads, thus decreasing the consumption of precious time and resources. This study demonstrates an optimized and proven screening technique in the discovery of two potential small molecule inhibitors of Zika virus Methyltransferase and RNA-dependent RNA polymerase. This in silico “per-residue energy decomposition pharmacophore” virtual screening approach will be critical in aiding scientists in the discovery of not only effective inhibitors of Zika viral targets, but also a wide range of anti-viral agents.

Keywords: NS5 protein inhibitors, per-residue decomposition, pharmacophore model, virtual screening, Zika virus

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1715 Biochemical and Antiviral Study of Peptides Isolated from Amaranthus hypochondriacus on Tomato Yellow Leaf Curl Virus Replication

Authors: José Silvestre Mendoza Figueroa, Anders Kvarnheden, Jesús Méndez Lozano, Edgar Antonio Rodríguez Negrete, Manuel Soriano García

Abstract:

Agroindustrial plants such as cereals and pseudo cereals offer a substantial source of biomacromolecules, as they contain large amounts per tissue-gram of proteins, polysaccharides and lipids in comparison with other plants. In particular, Amaranthus hypochondriacus seeds have high levels of proteins in comparison with other cereal and pseudo cereal species, which makes the plant a good source of bioactive molecules such as peptides. Geminiviruses are one principal class of pathogens that causes important economic losses in crops, affecting directly the development and production of the plant. One such virus is the Tomato yellow leaf curl virus (TYLCV), which affects mainly Solanacea family plants such as tomato species. The symptoms of the disease are curling of leaves, chlorosis, dwarfing and floral abortion. The aim of this work was to get peptides derived from enzymatic hydrolysis of globulins and albumins from amaranth seeds with specific recognition of the replication origin in the TYLCV genome, and to test the antiviral activity on host plants with the idea to generate a direct control of this viral infection. Globulins and albumins from amaranth were extracted, the fraction was enzymatically digested with papain, and the aromatic peptides fraction was selected for further purification. Six peptides were tested against the replication origin (OR) using affinity assays, surface resonance plasmon and fluorescent titration, and two of these peptides showed high affinity values to the replication origin of the virus, dissociation constant values were calculated and showed specific interaction between the peptide Ampep1 and the OR. An in vitro replication test of the total TYLCV DNA was performed, in which the peptide AmPep1 was added in different concentrations to the system reaction, which resulted in a decrease of viral DNA synthesis when the peptide concentration increased. Also, we showed that the peptide can decrease the complementary DNA chain of the virus in Nicotiana benthamiana leaves, confirming that the peptide binds to the OR and that its expected mechanism of action is to decrease the replication rate of the viral genome. In an infection assay, N. benthamiana plants were agroinfected with TYLCV-Israel and TYLCV-Guasave. After confirming systemic infection, the peptide was infiltrated in new infected leaves, and the plants treated with the peptide showed a decrease of virus symptoms and viral titer. In order to confirm the antiviral activity in a commercial crop, tomato plants were infected with TYLCV. After confirming systemic infection, plants were infiltrated with peptide solution as above, and the symptom development was monitored 21 days after treatment, showing that tomato plants treated with peptides had lower symptom rates and viral titer. The peptide was also tested against other begomovirus such as Pepper huasteco yellow vein virus (PHYVV-Guasave), showing a decrease of symptoms in N. benthamiana infected plants. The model of direct biochemical control of TYLCV infection shown in this work can be extrapolated to other begomovirus infections, and the methods reported here can be used for design of antiviral agrochemicals for other plant virus infections.

Keywords: agrochemical screening, antiviral, begomovirus, geminivirus, peptides, plasmon, TYLCV

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1714 Psychological Factors Predicting Social Distance during the COVID-19 Pandemic: An Empirical Investigation

Authors: Calogero Lo Destro

Abstract:

Numerous nations around the world are facing exceptional challenges in employing measures to stop the spread of COVID-19. Following the recommendations of the World Health Organization, a series of preventive measures have been adopted. However, individuals must comply with these rules and recommendations in order to make these measures effective. While COVID-19 was climaxing, it seemed of crucial importance to analyze which psychosocial factors contribute to the acceptance of such preventive behavior, thus favoring the management of COVID-19 worldwide health crisis. In particular, the identification of aspects related to obstacles and facilitation of adherence to social distancing has been considered crucial in the containment of the virus spread. Since the virus was firstly detected in China, Asian people could be considered a relevant outgroup targeted for exclusion. We also hypothesized social distance could be influenced by characteristics of the target, such as smiling or coughing. 260 participants participated in this research on a voluntary basis. They filled a survey designed to explore a series of COVID-19 measures (such as exposure to virus and fear of infection). We also assessed participants state and trait anxiety. The dependent variable was social distance, based on a measure of seating distance designed ad hoc for the present work. Our hypothesis that participants could report greater distance in response to Asian people was not confirmed. On the other hand, significantly lower distance in response to smiling compared to coughing targets was reported. Adopting a regression analysis model, we found that participants' social distance, in response to both coughing and smiling targets, was predicted by fear of infection and by the perception COVID-19 could become a pandemic. Social distance in response to the coughing target was also significantly and positively predicted by age and state anxiety. In summary, the present work has sought to identify a set of psychological variables, which may still be predictive of social distancing.

Keywords: COVID-19, social distancing, health, preventive behaviors, risk of infection

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1713 An Assessment of Health Hazards in Urban Communities: A Study of Spatial-Temporal Variations of Dengue Epidemic in Colombo, Sri Lanka

Authors: U. Thisara G. Perera, C. M. Kanchana N. K. Chandrasekara

Abstract:

Dengue is an epidemic which is spread by Aedes Egyptai and Aedes Albopictus mosquitoes. The cases of dengue show a dramatic growth rate of the epidemic in urban and semi urban areas spatially in tropical and sub-tropical regions of the world. Incidence of dengue has become a prominent reason for hospitalization and deaths in Asian countries, including Sri Lanka. During the last decade the dengue epidemic began to spread from urban to semi-urban and then to rural settings of the country. The highest number of dengue infected patients was recorded in Sri Lanka in the year 2016 and the highest number of patients was identified in Colombo district. Together with the commercial, industrial, and other supporting services, the district suffers from rapid urbanization and high population density. Thus, drainage and waste disposal patterns of the people in this area exert an additional pressure to the environment. The district is situated in the wet zone and thus low lying lands constitute the largest portion of the district. This situation additionally facilitates mosquito breeding sites. Therefore, the purpose of the present study was to assess the spatial and temporal distribution patterns of dengue epidemic in Kolonnawa MOH area (Medical Officer of Health) in the district of Colombo. The study was carried out using 615 recorded dengue cases in Kollonnawa MOH area during the south east monsoon season from May to September 2016. The Moran’s I and Kernel density estimation were used as analytical methods. The analysis of data was accomplished through the integrated use of ArcGIS 10.1 software packages along with Microsoft Excel analytical tool. Field observation was also carried out for verification purposes during the study period. Results of the Moran’s I index indicates that the spatial distribution of dengue cases showed a cluster distribution pattern across the area. Kernel density estimation emphasis that dengue cases are high where the population has gathered, especially in areas comprising housing schemes. Results of the Kernel Density estimation further discloses that hot spots of dengue epidemic are located in the western half of the Kolonnawa MOH area, which is close to the Colombo municipal boundary and there is a significant relationship with high population density and unplanned urban land use practices. Results of the field observation confirm that the drainage systems in these areas function poorly and careless waste disposal methods of the people further encourage mosquito breeding sites. This situation has evolved harmfully from a public health issue to a social problem, which ultimately impacts on the economy and social lives of the country.

Keywords: Dengue epidemic, health hazards, Kernel density, Moran’s I, Sri Lanka

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1712 Synthesis of an Organic-Inorganic Salt of (C2H5NO2) 2H4SiW12O40 and Investigation of Its Anti-Viral Effect on the Tobacco Mosaic Virus (TMV)

Authors: Mahboobeh Mohadeszadeh, Majid Saghi

Abstract:

Polyoxometalates (POMs) are important inorganic compounds that have been considered specifically in recent years due to abundant attributes and applications. Those POMs that have one central tetrahedral atom called keggin. The binding Amino-acid groups to keggin structure give the antivirus effect to these compounds. A new organic-inorganic hybrid structure, with formula (Gly)2H4SiW12O40 was synthesized. Investigation on Anti-viral effect of this compound showed the (Gly)2H4SiW12O40 prevents infection of Tobacco Mosaic Virus (TMV) on the Nicotianatabacum plants.

Keywords: Polyoxometalate, Keggin, Organic-inorganic salt, TMV

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1711 Synthesis of an Organic- Inorganic Salt of (C2H5NO2)2H4SiW12O40 and Investigation of Its Anti-Viral Effect on the Tobacco Mosaic Virus (TMV)

Authors: Mahboobeh Mohadeszadeh, Majid Saghi

Abstract:

Polyoxometalates (POMs) are important inorganic compounds that have been considered specifically in recent years due to abundant attributes and applications. Those POMs that have one central tetrahedral atom called keggin. The binding Amino-acid groups to keggin structure give the antivirus effect to these compounds. A new organic-inorganic hybrid structure, with formula (Gly)2H4SiW12O40 was synthesized. Investigation on Anti-viral effect of this compound showed the (Gly)2H4SiW12O40 prevents infection of Tobacco Mosaic Virus (TMV) on the Nicotianatabacum plants.

Keywords: polyoxometalate, keggin, organic-inorganic salt, TMV

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1710 Risk Factors for Postoperative Fever in Patients Undergoing Lumbar Fusion

Authors: Bang Haeyong

Abstract:

Purpose: The objectives of this study were to determine the prevalence, incidence, and risk factors for postoperative fever after lumbar fusion. Methods: This study was a retrospective chart review of 291 patients who underwent lumbar fusion between March 2015 and February 2016 at the Asan Medical Center. Information was extracted from electronic medical records. Postoperative fever was measured at Tmax > 37.7 ℃ and Tmax > 38.3 ℃. The presence of postoperative fever, blood culture, urinary excretion, and/or chest x-ray were evaluated. Patients were evaluated for infection after lumbar fusion. Results: We found 222 patients (76.3%) had a postoperative temperature of 37.7 ℃, and 162 patients (55.7%) had a postoperative temperature of 38.3 ℃ or higher. The percentage of febrile patients trended down following the mean 1.8days (from the first postoperative day to seventh postoperative day). Infection rate was 9 patients (3.1%), respiratory virus (1.7%), urinary tract infection (0.3%), phlebitis (0.3%), and surgical site infection (1.4%). There was no correlation between Tmax > 37.7℃ or Tmax > 38.3℃, and timing of fever, positive blood or urine cultures, pneumonia, or surgical site infection. Risk factors for increased postoperative fever following surgery were confirmed to be delay of defecation (OR=1.37, p=.046), and shorten of remove drainage (OR=0.66, p=.037). Conclusions: The incidence of fever was 76.3% after lumbar fusion and the drainage time was faster in the case of fever. It was thought that the bleeding was absorbed at the operation site and fever occurred. The prevalence of febrile septicemia was higher in patients with long bowel movements before surgery than after surgery. Clinical symptoms should be considered because postoperative fever cannot be determined by fever alone because fever and infection are not significant.

Keywords: lumbar surgery, fever, postoperative, risk factor

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1709 Synthesis of an Organic-Inorganic Salt of 12-Silicotungstate, (C2H5NO2)2H4SiW12O40 and Investigation of Its Anti-Viral Effect on the Tobacco Mosaic Virus

Authors: Mahboobeh Mohadeszadeh, Majid Saghi

Abstract:

Polyoxometalates (POMs) are important inorganic compounds that have been considered specifically in recent years due to abundant attributes and applications. Those POMs that have one central tetrahedral atom called keggin. The binding Amino-acid groups to keggin structure give the antivirus effect to these compounds. A new organic-inorganic hybrid structure, with formula (Gly)2H4SiW12O40, was synthesized. Investigation on the anti-viral effect of this compound showed the (Gly)2H4SiW12O40 prevents infection of Tobacco Mosaic Virus (TMV) on the Nicotianatabacum plants.

Keywords: polyoxometalate, keggin, organic-inorganic salt, TMV

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1708 Influenza Virus Circulation among the Population of Kazakhstan in 2012-2014

Authors: N. G. Klivleyeva, T. I. Glebova, G. V. Lukmanova, S. B. Bayseit, S. Z. Taubaeva, M. K. Kalkozhaeva

Abstract:

The role of viral diseases in the general infectious disease incidence increases every year and requires special attention to the problem of interpreting the etiology of infectious agents. Influenza and acute respiratory viral infections are one of the most pressing public health issues. In the period 2012-2014, collection of 419 nasal swabs and 150 blood sera has been carried out in the patient care institutions of the various Kazakhstan regions from patients with symptoms of ARVI and pneumonia. Primary identification of biosamples for the presence of influenza viral antigens in enzyme immunoassay on nitrocellulose membrane gave positive results in 125 swabs (29.8%). Biosample screening in immunofluorescence test revealed the presence of influenza viral antigens against A/H1 in 63 samples (15.0%), A/H3 – in 70 samples (16.7%) and type B – in 9 samples (2.1%). As a result of primary infection, and successive passages in chick embryos and MDCK cell cultures, 38 HAAg were isolated from 419 samples with a clear cytopathic effect and hemagglutination titre in MDCK cell culture within 1:2-1:4, in CE - 1:8-1:256. The infectivity of isolates in chicken embryos were 3.5-6.5 lg EID50/0.2, in MDCK cell culture – 2.5-6.5 lg PFU/ml. Identification of 28 isolates was carried out in inhibition reactions of hemagglutinating activity and neuraminidase activity, showed their belonging to the influenza virus: 26 strains to A/H1N1, one - to A/H3N2, and one - to type B. Serological examination of blood sera for the presence of specific antibodies being an indirect evidence of the performed isolation and contributing to the timely interpretation of the disease etiology in the epidemics takes an important place in the comprehensive study of influenza viruses circulating among people. Serological analyzes were carried out in HAI assay using a kit consisting of 12 reference strains obtained from the WHO centre for reference and research on Influenza (CDC, Atlanta, USA) and three Kazakhstan (A/Almaty/347/09 (H1N1v), A/Almaty/462/11 (H3N2) and B/Almaty/414/10) human influenza viruses that are stored in the laboratory collection. The results of serological analysis of 150 blood sera showed that antihaemagglutinins against the A/H3N2 virus serosubtype were found in 46 samples (49.4%) out of 93 sera collected in 2012-2013. The antibody titres were within 1:160-1:320. 19 sera (20.4%) were seropositive against influenza A/H1N1 virus, the antibodies were observed in titres of 1:20-1:40. Six sera (6.4%) were positive against the influenza A/H1N1+A/H3N2 virus (mixed infection); the antibodies were recorded in titres of 1:20-1:40. Antihaemagglutinins against influenza type B virus were detected only in five sera (5.4%). The results of analysis of 57 sera collected in 2014 showed that antihaemagglutinins against A/H3N2 virus subtype were detected in 32 blood sera (56.1%) in titres of 1:160-1:640. Ten sera (17.5%) were seropositive against A/H1N1 virus; antihaemagglutinins against influenza type B virus were not detected. Therefore, virological and serological studies have shown that in Kazakhstan, as well as in the world, the influenza viruses A/H1N1, A/H3N2 and influenza B viruses were actively circulating during the epidemic seasons in 2012-2014.

Keywords: influenza, MDCK cell, serological analysis, virus

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1707 Household Low Temperature MS2 (ATCC15597-B1) Virus Inactivation Using a Hot Bubble Column Evaporator

Authors: Adrian Garrido Sanchis, Richard Pashley

Abstract:

The MS2 (ATCC15597-B1) virus was used as a surrogate to estimate the inactivation rates for enteric viruses when using a hot air bubble column evaporator (HBCE) system in the treatment of household wastewater. In this study, we have combined MS2 virus surface charging properties with thermal inactivation rates, using an improved double layer plaque assay technique, in order to assess the efficiency of the HBCE process for virus removal in water. When bubbling a continuous flow of dry air, at 200°C, only heats the aqueous solution in the bubble column to about 50°C. Viruses are not inactivated by this solution temperature, as confirmed separately from water bath heating experiments. Hence, the efficiency of the HBCE process for virus removal in water appeared to be caused entirely by collisions between the hot air bubbles and the virus organisms. This new energy efficient treatment for water reuse applications can reduce the thermal energy required to only 25% (about 113.7 kJ/L) of that required for boiling (about 450 kJ/L).

Keywords: MS2 virus inactivation, water reuse, hot bubble column evaporator, water treatment

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1706 Novel p22-Monoclonal Antibody Based Blocking ELISA for the Detection of African Swine Fever Virus Antibodies in Serum

Authors: Ghebremedhin Tsegay, Weldu Tesfagaber, Yuanmao Zhu, Xijun He, Wan Wang, Zhenjiang Zhang, Encheng Sun, Jinya Zhang, Yuntao Guan, Fang Li, Renqiang Liu, Zhigao Bu, Dongming Zhao*

Abstract:

African swine fever (ASF) is a highly infectious viral disease of pigs, resulting in significant economic loss worldwide. As there is no approved vaccines and treatments, the control of ASF entirely depends on early diagnosis and culling of infected pigs. Thus, highly specific and sensitive diagnostic assays are required for accurate and early diagnosis of ASF virus (ASFV). Currently, only a few recombinant proteins have been tested and validated for use as reagents in ASF diagnostic assays. The most promising ones for ASFV antibody detection were p72, p30, p54, and pp62. So far, three ELISA kits based on these recombinant proteins have been commercialized. Due to the complex nature of the virus and variety forms of the disease, robust serodiagnostic assays are still required. ASFV p22 protein, encoded by KP177R gene, is located in the inner membrane of viral particle and appeared transiently in the plasma membrane early after virus infection. The p22 protein interacts with numerous cellular proteins, involved in processes of phagocytosis and endocytosis through different cellular pathways. However, p22 does not seem to be involved in virus replication or swine pathogenicity. In this study, E.coli expressed recombinant p22 protein was used to generate a monoclonal antibody (mAb), and its potential use for the development of blocking ELISA (bELISA) was evaluated. A total of 806 pig serum samples were tested to evaluate the bELISA. Acording the ROC (Reciever operating chracteristic) analysis, 100% sensitivity and 98.10% of specificity was recorded when the PI cut-off value was set at 47%. The novel assay was able to detect the antibodies as early as 9 days post infection. Finaly, a highly sensitive, specific and rapid novel p22-mAb based bELISA assay was developed, and optimized for detection of antibodies against genotype I and II ASFVs. It is a promising candidate for an early and acurate detection of the antibodies and is highly expected to have a valuable role in the containment and prevention of ASF.

Keywords: ASFV, blocking ELISA, diagnosis, monoclonal antibodies, sensitivity, specificity

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1705 Induction of Cellular and Humoral Immune Responses in BALB/c Mice Immunized With rB2L and rF1L Proteins of Orf Virus Adjuvanted With Alumina Nanoparticles

Authors: Alhaji Modu Bukar, Faez Firdaus Abdullah Jesse, Che Azurahanim Che Abdullah, Mustapha M. Noordin, Mohd-Lila Mohd Azmia

Abstract:

Orf virus (ORFV) is the causative agent of a proliferative skin lesion known as contagious ecthyma in sheep and goats. Currently used live attenuated vaccines against ORFV infection have been reported to cause severe outbreaks in vaccinated animals. In this study, we investigated the immunogenicity of the B2L and F1L proteins of the virus, which are thought to elicit a protective immune response The 6-week-old 50 female mice were divided into 8 groups: seven experimental groups and one control group. Each animal in the experimental group received an initial immunisation with the nanoparticles or proteins coated with the nanoparticles, followed by two booster immunizations with the same products 14 days apart. Ten days after the last booster inoculation, the mice were either humanely killed or lethally challenged with UPM /HSN-2-ORFV at a dose of 106 TCID50/mL in a volume of 50 μl. The spleen was examined for histopathological changes and quantification of T cells by flow cytometry. On the other hand, the degree of protection of mice from the lethal virus was evaluated by lesion size, weight loss, and histopathological examination of skin and liver. The results showed that mice immunised with rB2L alone, rB2L-Al₂O₃-NPs, rB2L/rF1L, and rB2L/rF1L-Al₂O₃-NPs elicited statistically higher levels of anti-rB2L and/or rF1L-specific IgA/IgG and CD4/CD8 cell immune responses than mice in the control groups (p < 0.01). The vaccine candidate did not exhibit severe skin damage after monitoring histopathology, morbidity, and mortality. Overall, the results suggest that recombinant rB2L and rF1L antigens may be useful universal vaccine candidates against ORFV infections.

Keywords: orf virus, antigen nanoparticles, virus, nanoparticles

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1704 Induction of HIV-1 Resistance: The New Approaches Based on Gene Modification and Stem Cell Engineering

Authors: Alieh Farshbaf

Abstract:

Introduction: Current anti-retroviral drugs have some restrictions for treatment of HIV-1 infection. The efficacy of retroviral drugs is not same in different infected patients and the virus rebound from latent reservoirs after stopping them. Recently, the engineering of stem cells and gene therapy provide new approaches to eliminate some drug problems by induction of resistance to HIV-1. Literature review: Up to now, AIDS-restriction genes (ARGs) were suitable candidate for gene and cell therapies, such as cc-chemokine receptor-5 (CCR5). In this manner, CCR5 provide effective cure in Berlin and Boston patients by inducing of HIV-1 resistance with allogeneic stem cell transplantation. It is showed that Zinc Finger Nuclease (ZFN) could induce HIV-1 resistance in stem cells of infected patients by homologous recombination or non-end joining mechanism and eliminate virus loading after returning the modified cells. Then, gene modification by HIV restriction factors, as TRIM5, introduced another gene candidate for HIV by interfering in infection process. These gene modifications/editing provided by stem cell futures that improve treatment in refractory disease such as HIV-1. Conclusion: Although stem cell transplantation has some complications, but in compare to retro-viral drugs demonstrated effective cure by elimination of virus loading. On the other hand, gene therapy is cost-effective for an infected patient than retroviral drugs payment in a person life-long. The results of umbilical cord blood stem cell transplantation showed that gene and cell therapy will be applied easier than previous treatment of AIDS with high efficacy.

Keywords: stem cell, AIDS, gene modification, cell engineering

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1703 Eradication of Apple mosaic virus from Corylus avellana L. via Cryotherapy and Confirmation of Virus-Free Plants via Reverse Transcriptase Polymerase Chain Reaction

Authors: Ergun Kaya

Abstract:

Apple mosaic virus (ApMV) is an ilarvirus causing harmful damages and product loses in many plant species. Because of xylem and phloem vessels absence, plant meristem tissues used for meristem cultures are virus-free, but sometimes only meristem cultures are not sufficient for virus elimination. Cryotherapy, a new method based on cryogenic techniques, is used for virus elimination. In this technique, 0.1-0.3mm meristems are excised from organized shoot apex of a selected in vitro donor plant and these meristems are frozen in liquid nitrogen (-196 °C) using suitable cryogenic technique. The aim of this work was to develop an efficient procedure for ApMV-free hazelnut via cryotherapy technique and confirmation of virus-free plants using Reverse Transcriptase-PCR technique. 100% virus free plantlets were obtained using droplet-vitrification method involved cold hardening in vitro cultures of hazelnut, 24 hours sucrose preculture of meristems on MS medium supplemented with 0.4M sucrose, and a 90 min PVS2 treatment in droplets.

Keywords: droplet vitrification, hazelnut, liquid nitrogen, PVS2

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1702 CNS Cryptococcoma in an Immunocompetent Adult from a Low Resource Setting: A Case Report

Authors: Ssembatya Joseph Mary

Abstract:

Introduction: Cryptococcal infection in the Central Nervous System (CNS) is frequently seen in human immunodeficiency virus (HIV) patients and others with low immunity as an opportunistic fungal infection. However, CNS cryptococcal granuloma (cryptococcoma) in immunocompetent patients is rare. We present a case of CNS cryptococcoma in an immunocompetent patient and review the literature to illustrate the diagnosis and treatment of such lesions. Case presentation: A 62-year-old, HIV-negative, immunocompetent female patient with no known chronic illness presented with 5 months history of a progressive headache associated with on and off episodic generalized tonic-clonic convulsions. She had been to several hospitals before she was referred to our center with a diagnosis of a brain tumor. Before referral and despite a negative CSF analysis result, she had received treatment for bacterial meningitis with no success. At Mbarara Regional Referral Hospital (MRRH), she had surgery with an excision biopsy which showed features consistent with cryptococcosis on histology. The patient had a successful adjuvant treatment with antifungal drugs following surgery. Conclusion: The diagnosis of a parasitic CNS infection, particularly cryptococcal infection mimicking neoplastic lesions in an immunocompetent patient, was unusual. Surgical management of such lesions from different reports has a bad outcome and management remains totally conservative.

Keywords: Cryptococcal meningitis, immunocompetent patient, Uganda, low resource setting

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1701 Estrogen Controls Hepatitis C Virus Entry and Spread through the GPR30 Pathway

Authors: Laura Ulitzky, Dougbeh-Chris Nyan, Manuel M. Lafer, Erica Silberstein, Nicoleta Cehan, Deborah R. Taylor

Abstract:

Hepatitis C virus (HCV)-associated hepatocellular carcinoma, fibrosis and cirrhosis are more frequent in men and postmenopausal women than in premenopausal women and women receiving hormone replacement therapy, suggesting that β-estradiol (estrogen) plays an innate role in preventing viral infection and liver disease. Estrogen classically acts through nuclear estrogen receptors or, alternatively, through the membrane-bound G-protein-coupled estrogen receptor (GPR30 or GPER). We observed a marked decrease in detectable virus when HCV-infected human hepatoma cells were treated with estrogen. The effect was mimicked by both Tamoxifen (Tam) and G1, a GPR30-specific agonist, and was reversed by the GPR30-specific antagonist, G15. Through GPR30, estrogen-mediated the down-regulation of occludin; a tight junction protein and HCV receptor, by promoting activation of matrix metalloproteinases (MMPs). Activated MMP-9 was secreted in response to estrogen, cleaving occludin in the extracellular Domain D, the motif required for HCV entry and spread. This pathway gives new insight into a novel innate immune pathway and the disparate host-virus responses to HCV demonstrated by the two sexes. Moreover, these data suggest that hormone replacement therapy may have beneficial antiviral properties for HCV-infected postmenopausal women and show promise for new antiviral treatments for both men and women.

Keywords: HCV, estrogen, occludin, MMPs

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1700 Stability Analysis of Modelling the Effect of Vaccination and Novel Quarantine-Adjusted Incidence on the Spread of Newcastle Disease

Authors: Nurudeen O. Lasisi, Sirajo Abdulrahman, Abdulkareem A. Ibrahim

Abstract:

Newcastle disease is an infection of domestic poultry and other bird species with the virulent Newcastle disease virus (NDV). In this paper, we study the dynamics of the modeling of the Newcastle disease virus (NDV) using a novel quarantine-adjusted incidence. The comparison of Vaccination, linear incident rate and novel quarantine-adjusted incident rate in the models are discussed. The dynamics of the models yield disease-free and endemic equilibrium states.The effective reproduction numbers of the models are computed in order to measure the relative impact of an individual bird or combined intervention for effective disease control. We showed the local and global stability of endemic equilibrium states of the models and we found that the stability of endemic equilibrium states of models are globally asymptotically stable if the effective reproduction numbers of the models equations are greater than a unit.

Keywords: effective reproduction number, Endemic state, Mathematical model, Newcastle disease virus, novel quarantine-adjusted incidence, stability analysis

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1699 Pyrethroid and Organophosphate Susceptibility Status of Aedesaegypti (Linnaeus), Aedes albopictus (Skuse) and Culex quinquefasciatus (Say) in Penang, Malaysia

Authors: Hadura Abu Hasan, Zairi Jaal, P. J. McCall

Abstract:

Dengue is a serious problem in Malaysia, particularly in high-density urban communities with lower socio-economic levels. This study evaluated the susceptibility of local populations of Aedesaegypti (Linnaeus), Aedesalbopictus (Skuse) and Culexquinquefasciatus (Say) from the traditional community of BaganDalam, Penang, Malaysia to lambdacyhalothrin and pirimiphos-methyl using standard World Health Organization (WHO) adult bioassay test. Unfed female mosquitoes aged 3-5 days were exposed to WHO recommended dosages of insecticides over fixed time periods with results presented as knock-down time (KT50) for each strain.The insecticide susceptible VCRU laboratory strain was usedas control. All three specieswere highly resistant to lambda-cyhalothrin with less than 10% mortality at 24 hours after treatment. In contrast, Ae.aegypti and Ae. albopictus were susceptible to pirimiphos-methyl, showing 100% mortality recorded 24 hoursafter treatment. Cx. quinquefasciatuswasclassed as ‘suspected resistant’ to pirimiphos-methyl as mortality recorded 24 hours after treatment was 94-96%. The results indicate that organophosphates such as pirimiphos-methyl might be used as alternative to pyrethroid for dengue vector control in this dengue-prone area.

Keywords: vector control, aedes aegypti, aedes albopictus, dengue, culex quinquefasciatus, residuals insecticides, pyrethroid, organophosphate, resistant, mosquito

Procedia PDF Downloads 237
1698 Entry Inhibitors Are Less Effective at Preventing Cell-Associated HIV-2 Infection than HIV-1

Authors: A. R. Diniz, P. Borrego, I. Bártolo, N. Taveira

Abstract:

Cell-to-cell transmission plays a critical role in the spread of HIV-1 infection in vitro and in vivo. Inhibition of HIV-1 cell-associated infection by antiretroviral drugs and neutralizing antibodies (NAbs) is more difficult compared to cell-free infection. Limited data exists on cell-associated infection by HIV-2 and its inhibition. In this work, we determined the ability of entry inhibitors to inhibit HIV-1 and HIV-2 cell-to cell fusion as a proxy to cell-associated infection. We developed a method in which Hela-CD4-cells are first transfected with a Tat expressing plasmid (pcDNA3.1+/Tat101) and infected with recombinant vaccinia viruses expressing either the HIV-1 (vPE16: from isolate HTLV-IIIB, clone BH8, X4 tropism) or HIV-2 (vSC50: from HIV-2SBL/ISY, R5 and X4 tropism) envelope glycoproteins (M.O.I.=1 PFU/cell).These cells are added to TZM-bl cells. When cell-to-cell fusion (syncytia) occurs the Tat protein diffuses to the TZM-bl cells activating the expression of a reporter gene (luciferase). We tested several entry inhibitors including the fusion inhibitors T1249, T20 and P3, the CCR5 antagonists MVC and TAK-779, the CXCR4 antagonist AMD3100 and several HIV-2 neutralizing antibodies (Nabs). All compounds inhibited HIV-1 and HIV-2 cell fusion albeit to different levels. Maximum percentage of HIV-2 inhibition (MPI) was higher for fusion inhibitors (T1249- 99.8%; P3- 95%, T20-90%) followed by co-receptor antagonists (MVC- 63%; TAK-779- 55%; AMD3100- 45%). NAbs from HIV-2 infected patients did not prevent cell fusion up to the tested concentration of 4μg/ml. As for HIV-1, MPI reached 100% with TAK-779 and T1249. For the other antivirals, MPIs were: P3-79%; T20-75%; AMD3100-61%; MVC-65%.These results are consistent with published data. Maraviroc had the lowest IC50 both for HIV-2 and HIV-1 (IC50 HIV-2= 0.06 μM; HIV-1=0.0076μM). Highest IC50 were observed with T20 for HIV-2 (3.86μM) and with TAK-779 for HIV-1 (12.64μM). Overall, our results show that entry inhibitors in clinical use are less effective at preventing Env mediated cell-to-cell-fusion in HIV-2 than in HIV-1 which suggests that cell-associated HIV-2 infection will be more difficult to inhibit compared to HIV-1. The method described here will be useful to screen for new HIV entry inhibitors.

Keywords: cell-to-cell fusion, entry inhibitors, HIV, NAbs, vaccinia virus

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1697 Comprehensive Evaluation of Oral and Maxillofacial Radiology in "COVID-19"

Authors: Sahar Heidary, Ramin Ghasemi Shayan

Abstract:

The recent coronavirus disease 2019 (COVID-19) occurrence has carried considerabletrials to the world health system, comprising the training of dental and maxillofacial radiology (DMFR). DMFR will keep avital role in healthcare throughout this disaster. Severe acute breathing disease coronavirus 2 (SARS-CoV-2), the virus producing the current coronavirus disease 2019 (COVID-19) pandemic, is not only extremely contagious but can make solemn consequences in susceptible persons comprising dental patients and dental health care personnel (DHCPs). Reactions to COVID-19 have been available by the Cores for Infection Switch and Inhibition and the American Dental Association, but a more detailed answer is necessary for the harmless preparation of oral and maxillofacial radiology. Our goal is to evaluation the existing information just how the illness threatens patients and DHCPs and how to define which patients are possible to be SARS-CoV-2 infected; study how the usage of private shielding utensils and contamination control measures based on recent top observes, and knowledge can decrease the danger of virus spread in radiologic trials; and scrutinize how intraoral radiography, with its actually superior danger of scattering the infection, might be changed by extraoralradiographic methods for definite diagnostic jobs. In the pandemic, teleradiology has been extensively recycled for diagnostic determinations of COVID-19 patients, for discussions with radiologists in crisis cases, or managing of distance among radiology clinics. Dentists can have the digital radiographic images of their emergency patients through online service area also by electronic message or messaging applications to view in their smart phones, laptops, or other electronic devices.

Keywords: radiology, dental, oral, COVID-19, infection

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1696 Haplotypes of the Human Leukocyte Antigen-G Different HIV-1 Groups from the Netherlands

Authors: A. Alyami, S. Christmas, K. Neeltje, G. Pollakis, B. Paxton, Z. Al-Bayati

Abstract:

The Human leukocyte antigen-G (HLA-G) molecule plays an important role in immunomodulation. To date, 16 untranslated regions (UTR) HLA-G haplotypes have been previously defined by sequenced SNPs in the coding region. From these, UTR-1, UTR-2, UTR-3, UTR-4, UTR-5, UTR-6 and UTR-7 are the most frequent 3’UTR haplotypes at the global level. UTR-1 is associated with higher levels of soluble HLA-G and HLA-G expression, whereas UTR-5 and UTR-7 are linked with low levels of soluble HLA-G and HLA-G expression. Human immunodeficiency virus type 1 (HIV-1) infection results in the progressive loss of immune function in infected individuals. The virus escape mechanism typically includes T lymphocytes and NK cell recognition and lyses by classical HLA-A and B down-regulation, which has been associated with non-classical HLA-G molecule up-regulation, respectively. We evaluated the haplotypes of the HLA-G 3′ untranslated region frequencies observed in three HIV-1 groups from the Netherlands and their susceptibility to develop infection. The three groups are made up of mainly men who have sex with men (MSM), injection drug users (IDU) and a high-risk-seronegative (HRSN) group. DNA samples were amplified with published primers prior sequencing. According to our results, the low expresser frequencies show higher in HRSN compared to other groups. This is indicating that 3’UTR polymorphisms may be identified as potential prognostic biomarkers to determine susceptibility to HIV.

Keywords: Human leukocyte antigen-G (HLA-G) , men who have sex with men (MSM), injection drug users (IDU), high-risk-seronegative (HRSN) group, high-untranslated region (UTR)

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1695 Nanocomplexes on the Base of Triterpene Saponins Isolated from Glycyrrhiza glabra and Saponaria officinalis Plants as an Efficient Adjuvants for Influenza Vaccine Use

Authors: Vladimir Berezin, Andrey Bogoyavlenskiy, Pavel Alexyuk, Madina Alexyuk, Aizhan Turmagambetova, Irina Zaitseva, Nadezhda Sokolova, Elmira Omirtaeva

Abstract:

Introduction: Triterpene saponins of plant origin are one of the most promising candidates for elaboration of novel adjuvants. Due to the combination of immunostimulating activity and the capacity interact with amphipathic molecules with formation of highly immunogenic nanocomplexes, triterpene saponins could serve as a good adjuvant/delivery system for vaccine use. In the research presented adjuvants on the base of nanocomplexes contained triterpene saponins isolated from Glycyrrhiza glabra and Saponaria officinalis plants indigenous to Kazakhstan were elaborated for influenza vaccine use. Methods: Purified triterpene saponins 'Glabilox' and 'SO1' with low toxicity and high immunostimulatory activity were isolated from plants Glycyrrhiza glabra L. and Saponaria officinalis L. by high-performance liquid chromatography (HPLC) and identified using electrospray ionization mass spectrometry (ESI-MS). Influenza virus A/St-Petersburg/5/09 (H1N1) propagated in 9-days old chicken embryos was concentrated and purified by centrifugation in sucrose gradient. Nanocomplexes contained lipids, and triterpene saponins Glabilox or SO1 were prepared by dialysis technique. Immunostimulating activity of experimental vaccine preparations was studied in vaccination/challenge experiments in mice. Results: Humoral and cellular immune responses and protection against influenza virus infection were examined after single subcutaneous and intranasal immunization. Mice were immunized subunit influenza vaccine (HA+NA) or whole virus inactivated influenza vaccine in doses 3.0/5.0/10.0 µg antigen/animal mixed with adjuvant in dose 15.0 µg/animal. Sera were taken 14-21 days following single immunization and mice challenged by A/St-Petersburg/5/09 influenza virus in dose 100 EID₅₀. Study of experimental influenza vaccine preparations in animal immunization experiments has shown that subcutaneous and intranasal immunization with subunit influenza vaccine mixed with nanocomplexes contained Glabilox or SO1 saponins stimulated high levels of humoral immune response (IgM, IgA, IgG1, IgG2a, and IgG2b antibody) and cellular immune response (IL-2, IL-4, IL-10, and IFN-γ cytokines) and resulted 80-90% protection against lethal influenza infection. Also, single intranasal and single subcutaneous immunization with whole virus inactivated influenza vaccine mixed with nanoparticulated adjuvants stimulated high levels of humoral and cellular immune responses and provided 100% protection against lethal influenza infection. Conclusion: The results of study have shown that nanocomplexes contained purified triterpene saponins Glabilox and SO1 isolated from plants indigenous to Kazakhstan can stimulate a broad spectrum of humoral and cellular immune responses and induce protection against lethal influenza infection. Both elaborated adjuvants are promising for incorporation to influenza vaccine intended for subcutaneous and intranasal routes of immunization.

Keywords: influenza vaccine, adjuvants, triterpene saponins, immunostimulating activity

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1694 Computational Prediction of the Effect of S477N Mutation on the RBD Binding Affinity and Structural Characteristic, A Molecular Dynamics Study

Authors: Mohammad Hossein Modarressi, Mozhgan Mondeali, Khabat Barkhordari, Ali Etemadi

Abstract:

The COVID-19 pandemic, caused by SARS-CoV-2, has led to significant concerns worldwide due to its catastrophic effects on public health. The SARS-CoV-2 infection is initiated with the binding of the receptor-binding domain (RBD) in its spike protein to the ACE2 receptor in the host cell membrane. Due to the error-prone entity of the viral RNA-dependent polymerase complex, the virus genome, including the coding region for the RBD, acquires new mutations, leading to the appearance of multiple variants. These variants can potentially impact transmission, virulence, antigenicity and evasive immune properties. S477N mutation located in the RBD has been observed in the SARS-CoV-2 omicron (B.1.1. 529) variant. In this study, we investigated the consequences of S477N mutation at the molecular level using computational approaches such as molecular dynamics simulation, protein-protein interaction analysis, immunoinformatics and free energy computation. We showed that displacement of Ser with Asn increases the stability of the spike protein and its affinity to ACE2 and thus increases the transmission potential of the virus. This mutation changes the folding and secondary structure of the spike protein. Also, it reduces antibody neutralization, raising concern about re-infection, vaccine breakthrough and therapeutic values.

Keywords: S477N, COVID-19, molecular dynamic, SARS-COV2 mutations

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