Squint Among Adult Population in Hail City, Saudi Arabia

Background: Strabismus, also known as crossed eyes, is a condition in which the eyes do not properly align with each other when looking at an object. If present during a large part of childhood, it may result in amblyopia. If onset is during adulthood, it is more likely to result in double vision. Objective: The aim of the study was to estimate the prevalence of squint, types and treatment characteristics in the studied adults in Hail city, Saudi Arabia. Methods: A cross-sectional study conducted in Hail city, Saudi Arabia. The study included 294 participants; 95 male and 199 female adults aged >20 years. The study period was from 1 January to 30 April 2018. Data collected by personal interview using a pre-designed questionnaire, which distributed among the participants to be self-reported. Results: The prevalence of squint among the studied population was 9.9%. it was more common in females than males. Squint was right sided in 24.1% of the cases, left sided in 51.7% and in both eyes in 24.1% of the studied cases. About half (44.8%) of cases had inward squint (esotropia) and 10.3% outward squint (exsotropia), 24.1% of the cases had Intermittent squint and 6.9% had permanent squint. Most (55.2%) of squint cases use glasses and 34.5% of cases squint affected their visual acuity. In 6.9%, squint causes psychological troubles. As regards treatment, 20.7% received medical treatment and 17.2% received surgical treatment but 62.1% do not seek medical care. Only 10.3% of cases completely cured and 13.8% had recurrence. There was insignificant relation with age, sex, education, squint in parents, chronic diseases, consanguinity or hereditary diseases (P>0.05). Conclusion: in this study, the prevalence of squint in the adult participants in Hail city, Saudi Arabia was 9.9% but 62.1% do not seek medical care. After treatment, only 10.3% of cases completely cured and 13.8% had recurrence. Health education of the public about importance of early treatment is highly recommended. Keywords: Squint; strabismus; adult population; prevalence; types; Hail; Saudi Arabia

ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice.

The Middle East respiratory syndrome coronavirus (MERS-CoV) has infected more than 1900 humans, since 2012. The syndrome ranges from asymptomatic and mild cases to severe pneumonia and death. The virus is believed to be circulating in dromedary camels without notable symptoms since the 1980s. Therefore, dromedary camels are considered the only animal source of infection. Neither antiviral drugs nor vaccines are approved for veterinary or medical use despite active research on this area. Here, we developed four vaccine candidates against MERS-CoV based on ChAdOx1 and MVA viral vectors, two candidates per vector. All vaccines contained the full-length spike gene of MERS-CoV; ChAdOx1 MERS vaccines were produced with or without the leader sequence of the human tissue plasminogen activator gene (tPA) where MVA MERS vaccines were produced with tPA, but either the mH5 or F11 promoter driving expression of the spike gene. All vaccine candidates were evaluated in a mouse model in prime only or prime-boost regimens. ChAdOx1 MERS with tPA induced higher neutralising antibodies than ChAdOx1 MERS without tPA. A single dose of ChAdOx1 MERS with tPA elicited cellular immune responses as well as neutralising antibodies that were boosted to a significantly higher level by MVA MERS. The humoral immunogenicity of a single dose of ChAdOx1 MERS with tPA was equivalent to two doses of MVA MERS (also with tPA). MVA MERS with mH5 or F11 promoter induced similar antibody levels; however, F11 promoter enhanced the cellular immunogenicity of MVA MERS to significantly higher magnitudes. In conclusion, our study showed that MERS-CoV vaccine candidates could be optimized by utilising different viral vectors, various genetic designs of the vectors, or different regimens to increase immunogenicity. ChAdOx1 and MVA vectored vaccines have been safely evaluated in camels and humans and these MERS vaccine candidates should now be tested in camels and in clinical trials

ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice.

The Middle East respiratory syndrome coronavirus (MERS-CoV) has infected more than 1900 humans, since 2012. The syndrome ranges from asymptomatic and mild cases to severe pneumonia and death. The virus is believed to be circulating in dromedary camels without notable symptoms since the 1980s. Therefore, dromedary camels are considered the only animal source of infection. Neither antiviral drugs nor vaccines are approved for veterinary or medical use despite active research on this area. Here, we developed four vaccine candidates against MERS-CoV based on ChAdOx1 and MVA viral vectors, two candidates per vector. All vaccines contained the full-length spike gene of MERS-CoV; ChAdOx1 MERS vaccines were produced with or without the leader sequence of the human tissue plasminogen activator gene (tPA) where MVA MERS vaccines were produced with tPA, but either the mH5 or F11 promoter driving expression of the spike gene. All vaccine candidates were evaluated in a mouse model in prime only or prime-boost regimens. ChAdOx1 MERS with tPA induced higher neutralising antibodies than ChAdOx1 MERS without tPA. A single dose of ChAdOx1 MERS with tPA elicited cellular immune responses as well as neutralising antibodies that were boosted to a significantly higher level by MVA MERS. The humoral immunogenicity of a single dose of ChAdOx1 MERS with tPA was equivalent to two doses of MVA MERS (also with tPA). MVA MERS with mH5 or F11 promoter induced similar antibody levels; however, F11 promoter enhanced the cellular immunogenicity of MVA MERS to significantly higher magnitudes. In conclusion, our study showed that MERS-CoV vaccine candidates could be optimized by utilising different viral vectors, various genetic designs of the vectors, or different regimens to increase immunogenicity. ChAdOx1 and MVA vectored vaccines have been safely evaluated in camels and humans and these MERS vaccine candidates should now be tested in camels and in clinical trials

Transcriptomics-based characterization of the toxicity of ZnO nanoparticles against chronic myeloid leukemia cells

Introduction: Zinc oxide nanoparticles (ZnO NPs) have recently attracted attention as potential anti-cancer agents. To the best of our knowledge, the toxicity of ZnO NPs against human chronic myeloid leukemia cells (K562 cell line) has not been studied using transcriptomics approach. Objective: The goals of this study were to evaluate the capability of ZnO NPs to induce apoptosis in human chronic myeloid leukemia cells (K562 cells) and to investigate the putative mechanisms of action. Methods: We used viability assay and flowcytometry coupled with Annexin V-FITC and propidium iodide to investigate the toxicity of ZnO NPs on K562 cells and normal peripheral blood mononuclear cells. Next we utilized a DNA microarray-based transcriptomics approach to characterize the ZnO NPs-induced changes in the transcriptome of K562 cells. Results: ZnO NPs exerted a selective toxicity (mainly by apoptosis) on the leukemic cells (p≤ 0.005) and altered their transcriptome; 429 differentially expressed genes (DEGs) with fold change (FC)≥ 4 and p≤ 0.008 with corrected p≤ 0.05 were identified in K562 cells post treatment with ZnO NPs. The over-expressed genes were implicated in “response to zinc”, “response to toxic substance” and “negative regulation of growth” (corrected p≤ 0.05). In contrast, the repressed genes positively regulated “cell proliferation”, “cell migration”, “cell adhesion”, “receptor signaling pathway via JAK-STAT” and “phosphatidylinositol 3-kinase signaling” (corrected p≤ 0.05). Lowering the FC to ≥ 1.5 with p≤ 0.05 and corrected p≤ 0.1 showed that ZnO NPs over-expressed the anti-oxidant defense system, drove K562 cells to undergo mitochondrial-dependent apoptosis, and targeted NF-κB pathway. Conclusion: Taken together, our findings support the earlier studies that reported anti-cancer activity of ZnO NPs and revealed possible molecular mechanisms employed by ZnO NPs to induce apoptosis in K562 cells

Humoral Immunogenicity and Efficacy of a Single Dose of ChAdOx1 MERS Vaccine Candidate in Dromedary Camels

MERS-CoV seronegative and seropositive camels received a single intramuscular dose of ChAdOx1 MERS, a replication-deficient adenoviral vectored vaccine expressing MERS-CoV spike protein, with further groups receiving control vaccinations. Infectious camels with active naturally acquired MERS-CoV infection, were co-housed with the vaccinated camels at a ratio of 1:2 (infected:vaccinated); nasal discharge and virus titres were monitored for 14 days. Overall, the vaccination reduced virus shedding and nasal discharge (p = 0.0059 and p = 0.0274, respectively). Antibody responses in seropositive camels were enhancedby the vaccine; these camels had a higher average age than seronegative. Older seronegative camels responded more strongly to vaccination than younger animals; and neutralising antibodies were detected in nasal swabs. Further work is required to optimise vaccine regimens for younger seronegative camels

Seroprevalence of SARS-CoV-2 (COVID-19) among Healthcare Workers in Saudi Arabia: Comparing Case and Control Hospitals

Healthcare workers (HCWs) stand at the frontline for fighting coronavirus disease 2019 (COVID-19) pandemic. This puts them at higher risk of acquiring the infection than other individuals in the community. Defining immunity status among health care workers is therefore of interest since it helps to mitigate the exposure risk. This study was conducted between May 20th and 30th, 2020. Eighty-five hospitals across Kingdom of Saudi Arabia were divided into 2 groups: COVID-19 referral hospitals are those to which RT-PCR-confirmed COVID-19 patients were admitted or referred for management (Case-hospitals). COVID-19 nonaffected hospitals where no COVID-19 patients had been admitted or managed and no HCW outbreak (Control hospitals). Next, seroprevalence of severe acute respiratory syndrome coronavirus 2 among HCWs was evaluated; there were 12,621 HCWs from the 85 hospitals. There were 61 case-hospitals with 9379 (74.3%) observations, and 24 control-hospitals with 3242 (25.7%) observations. The overall positivity rate by the immunoassay was 299 (2.36%) with a significant difference between the case-hospital (2.9%) and the control-group (0.8%) (P value <0.001). There was a wide variation in the positivity rate between regions and/or cities in Saudi Arabia, ranging from 0% to 6.31%. Of the serology positive samples, 100 samples were further tested using the SAS2pp neutralization assay; 92 (92%) samples showed neutralization activity. The seropositivity rate in Kingdom of Saudi Arabia is low and varies across different regions with higher positivity in case-hospitals than control-hospitals. The lack of neutralizing antibodies (NAb) in 8% of the tested samples could mean that assay is a more sensitive assay or that neutralization assay has a lower detection limits; or possibly that some samples had cross-reaction to spike protein of other coronaviruses in the assay, but these were not specific to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Expression and Cellular Immunogenicity of a Transgenic Antigen Driven by Endogenous Poxviral Early Promoters at Their Authentic Loci in MVA

CD8+ T cell responses to vaccinia virus are directed almost exclusively against early gene products. The attenuated strain modified vaccinia virus Ankara (MVA) is under evaluation in clinical trials of new vaccines designed to elicit cellular immune responses against pathogens including Plasmodium spp., M. tuberculosis and HIV-1. All of these recombinant MVAs (rMVA) utilize the well-established method of linking the gene of interest to a cloned poxviral promoter prior to insertion into the viral genome at a suitable locus by homologous recombination in infected cells. Using BAC recombineering, we show that potent early promoters that drive expression of non-functional or non-essential MVA open reading frames (ORFs) can be harnessed for immunogenic expression of recombinant antigen. Precise replacement of the MVA orthologs of C11R, F11L, A44L and B8R with a model antigen positioned to use the same translation initiation codon allowed early transgene expression similar to or slightly greater than that achieved by the commonly-used p7.5 or short synthetic promoters. The frequency of antigen-specific CD8+ T cells induced in mice by single shot or adenovirus-prime, rMVA-boost vaccination were similarly equal or marginally enhanced using endogenous promoters at their authentic genomic loci compared to the traditional constructs. The enhancement in immunogenicity observed using the C11R or F11L promoters compared with p7.5 was similar to that obtained with the mH5 promoter compared with p7.5. Furthermore, the growth rates of the viruses were unimpaired and the insertions were genetically stable. Insertion of a transgenic ORF in place of a viral ORF by BAC recombineering can thus provide not only a potent promoter, but also, concomitantly, a suitable insertion site, potentially facilitating development of MVA vaccines expressing multiple recombinant antigens

Poxviral promoters for improving the immunogenicity of MVA delivered vaccines

Modified vaccinia virus Ankara (MVA) is a replication-deficient poxvirus, attenuated in chick embryo fibroblast primary cells. It has been utilised as a viral vector to develop many vaccines against cancer and infectious diseases such as malaria, HIV/AIDS, influenza, and tuberculosis, MERS-CoV, and Ebola virus infection. There is accumulating data from many preclinical and clinical studies that highlights the excellent safety and immunogenicity of MVA. However, due to the complex nature of many pathogens and their pathogenicity, MVA vectored vaccine candidates need to be optimised to improve their immunogenicity. One of the main approaches to improve MVA immunogenicity focuses on optimising poxviral promoters that drive recombinant vaccine antigens, encoded within recombinant MVA vector genome. A number of promoters were described or optimised to improve the development of MVA based vaccines such as p7.5, pF11, and mH5 promoters. This review focuses on poxviral promoters, their optimisation, genetic stability, and clinical use

SAUDI LEARNERS’ PRONUNCIATION DIFFICULTIES WITH THE ENGLISH VOICELESS BILABIAL STOP /p/

This study investigated the production of the English voiceless bilabial stop /p/ in three word positions (initial, medial, and final). By a group of 20 male and female ESL Saudi Arabian learners in the United States. The stimulus of this work was a list of 20 English words with an equal number of words for the three word positions initial, medial, and final. By measuring the Voice Onset Time in word initial and the duration of the release of the target phoneme /p/ in word medial and final positions this study identified several types of error in the participants’ utterances, including substitution of /p/ with /b/, approximation, and frication. The position of /p/ in words had a significant effect on the accuracy of pronunciation as the position that yielded the highest level of accuracy was the final position. The other two positions, initial and medial, showed a significantly higher number of production errors than word- final position

Preparedness and response to COVID-19 in Saudi Arabia: Building on MERS experience

Nearly four months have passed since the emergence of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which caused the rapidly spreading Coronavirus Disease 2019 (COVID-19) pandemic. To date, there have been more than 2.3 million confirmed cases and more than 160,000 deaths globally caused by COVID-19. Chinese health authorities, where the virus emerged, have taken prompt strict public health measures to control and prevent the spread of the outbreak. In Saudi Arabia, unprecedented precautionary strict measures were applied to prevent virus entry to the country or to mitigate its impact when it arrives. Here, we review the response of Saudi Arabia to COVID-19 pandemic and how did the experience learned from the Middle East respiratory syndrome coronavirus (MERS-CoV) epidemic since 2012 has helped the country to be better prepared for the current COVID-19 pandemic. We also discuss the country readiness, improvement in research and development, and the unprecedented rapid precautionary measures that have been taken by the Saudi government thus far