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1.
Cancer Control ; 31: 10732748241248032, 2024.
Article in English | MEDLINE | ID: mdl-38717601

ABSTRACT

INTRODUCTION: Cancer Health literacy (CHL) is the health literacy related to cancer knowledge, prevention, treatment, screening, and access to services. It is an important indicator of people's adherence to screening and preventive measures, which helps to reduce the incidence and prevalence of cancer. The study assessed the CHL level and its association with relevant socio-demographic characteristics and sources of information among primary health care patients and visitors in the United Arab Emirates (UAE). METHODS: A cross-sectional study recruited survey participants who consented to respond to an interviewer-administered questionnaire. The assessment of CHL was done by using 15 questions. CHL level was measured as a median score and also categorized as poor/inadequate, moderate, good/excellent. Nominal logistic regression was used to analyze the relationship between CHL categories and participants' sociodemographic characteristics and CHL sources of information. RESULTS: Of the total 492 participants, 45.5% were young adults (30-39 years old), 32.9% were males, and 70.8% were UAE nationals. The overall median CHL score was 8.0 (IQR = 5.0-10). 33.7% of the participants had a poor/inadequate level of CHL, 49.6% had a moderate level and 16.7% had a good to excellent level of CHL. 76.9% of the participants knew the importance of early cancer screening tests, 72.7% acknowledged the metastatic capacity of cancer, and the protective factors of cancer, especially, in colon cancer (71.7%). A high proportion of participants received health information about cancer via the internet (50.7%), television (45.3%), social media (40.2%), and doctors (43.6%). Nationality other than UAE (aOR = 1.62, 95% CI = 1.03-2.56, P = .038), having university education (aOR = 2.20, 95% CI = 1.21-3.99, P = .010) compared to those with lower than high school, and having a family history of cancer (aOR = 2.42, 95% CI = 1.33-4.41, P = .004) were positively associated with CHL. Older age (aOR = .36, 95% CI = .17-.75, P = .007 for 50-59 years, and aOR = .29, 95% CI = .11-.82, P = .019) for 60-69 years, higher-income (aOR = .57, 95% CI = .33-.99, P = .047 for 10,000-19,999 AED; aOR = .53, 95% CI = .33-.88, P = .013 for ≥20,000) compared with those earning <10,000 AED were negatively associated with CHL. CONCLUSIONS: CHL among the resident UAE population was moderately adequate, therefore implementation of awareness campaigns seems to be warranted. Moreover, evaluation research targeting the CHL impact on cancer prevention practices and screening is also advocated.


Subject(s)
Health Literacy , Neoplasms , Humans , United Arab Emirates/epidemiology , Health Literacy/statistics & numerical data , Female , Male , Cross-Sectional Studies , Adult , Neoplasms/epidemiology , Neoplasms/prevention & control , Middle Aged , Surveys and Questionnaires , Health Knowledge, Attitudes, Practice , Early Detection of Cancer/statistics & numerical data , Young Adult
2.
BMJ Open ; 14(4): e082654, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38626976

ABSTRACT

BACKGROUND: Globally, cardiovascular disease (CVD) remains the leading cause of death, warranting effective management and prevention measures. Risk prediction tools are indispensable for directing primary and secondary prevention strategies for CVD and are critical for estimating CVD risk. Machine learning (ML) methodologies have experienced significant advancements across numerous practical domains in recent years. Several ML and statistical models predicting CVD time-to-event outcomes have been developed. However, it is not known as to which of the two model types-ML and statistical models-have higher discrimination and calibration in this regard. Hence, this planned work aims to systematically review studies that compare ML with statistical methods in terms of their predictive abilities in the case of time-to-event data with censoring. METHODS: Original research articles published as prognostic prediction studies, which involved the development and/or validation of a prognostic model, within a peer-reviewed journal, using cohort or experimental design with at least a 12-month follow-up period will be systematically reviewed. The review process will adhere to the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies checklist. ETHICS AND DISSEMINATION: Ethical approval is not required for this review, as it will exclusively use data from published studies. The findings of this study will be published in an open-access journal and disseminated at scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42023484178.


Subject(s)
Cardiovascular Diseases , Humans , Cardiovascular Diseases/prevention & control , Systematic Reviews as Topic , Prognosis , Machine Learning , Research Design , Review Literature as Topic
3.
STAR Protoc ; 5(1): 102913, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38393950

ABSTRACT

Leakage of mitochondrial or nuclear DNA into the cytosol can occur following viral infections, radiation damage, and some cancers. Here, we present an optimized protocol for isolating and quantifying cytosolic DNA from mammalian cells. We describe steps for collecting cytosolic fractions from cells, extracting DNA using columns, and quantifying extracted DNA using qPCR. This straightforward protocol can be completed in as little as 5 hours, and allows for the identification of the source of DNA. For complete details on the use and execution of this protocol, please refer to Jahun et al.1.


Subject(s)
DNA , Mitochondria , Animals , Cytosol , Mammals/genetics
4.
Viruses ; 16(2)2024 02 03.
Article in English | MEDLINE | ID: mdl-38400023

ABSTRACT

Human sapoviruses (HuSaVs) and noroviruses are considered the leading cause of acute gastroenteritis worldwide. While extensive research has focused on noroviruses, our understanding of sapoviruses (SaVs) and their interactions with the host's immune response remains limited. HuSaVs have been challenging to propagate in vitro, making the porcine sapovirus (PSaV) Cowden strain a valuable model for studying SaV pathogenesis. In this study we show, for the first time, that PSaV Cowden strain has mechanisms to evade the host's innate immune response. The virus 3C-like protease (NS6) inhibits type I IFN production by targeting TBK1. Catalytically active NS6, both during ectopic expression and during PSaV infection, targets TBK1 which is then led for rapid degradation by the proteasome. Moreover, deletion of TBK1 from porcine cells led to an increase in PSaV titres, emphasizing its role in regulating PSaV infection. Additionally, we successfully established PSaV infection in IPEC-J2 cells, an enterocytic cell line originating from the jejunum of a neonatal piglet. Overall, this study provides novel insights into PSaV evasion strategies, opening the way for future investigations into SaV-host interactions, and enabling the use of a new cell line model for PSaV research.


Subject(s)
Caliciviridae Infections , Sapovirus , Animals , Cell Line , Gene Expression , Immunity, Innate , Peptide Hydrolases , Protein Serine-Threonine Kinases , Sapovirus/genetics , Swine
5.
Inj Prev ; 30(2): 108-113, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-37940378

ABSTRACT

INTRODUCTION: Motor vehicle collisions are a major cause of death and injury among pregnant women and their fetuses. Seat belt use compliance during pregnancy varies in different populations. We aimed to study seat belt use among pregnant women and factors affecting seat belt use during pregnancy in Al Ain City, the United Arab Emirates. METHODS: This cross-sectional analysis used the baseline data collected from pregnant women participating in the Mutaba'ah Study from May 2017 to November 2022. Data were collected using self-administered questionnaires. Variables included sociodemographic, gestation periods and seat belt-related information. All pregnant women who responded to the questions related to seat belt use were included (N=2354). RESULTS: Seat belt use before and during pregnancy was estimated at 69.7% (95% CI 67.9% to 71.6%) and 65.5% (95% CI 63.6% to 67.4%), respectively. The reasons for not using seat belts during pregnancy included being uncomfortable to wear, habitual non-use and considering them unsafe for pregnancy. Age, higher levels of education of the pregnant woman or her spouse, being employed, having a sufficient household income, lower gestational age, and using a seat belt before pregnancy were positively associated with using a seat belt during pregnancy in the bivariate analyses. Pregnant women in their third trimester had independently significant lower odds of using a seat belt compared with those in the first trimester (OR 0.42, 95% CI 0.24 to 0.76). CONCLUSIONS: The findings indicate decreased compliance with seat belt use during pregnancy and as gestation progressed. The decrease was related to several reasons, including feeling uncomfortable wearing seat belts, habitual non-use and unsafe for pregnancy, necessitating appropriate measures to increase awareness. Raising public awareness about the advantages of wearing seat belts during pregnancy and the involvement of healthcare professionals in educating pregnant women are warranted.


Subject(s)
Pregnant Women , Seat Belts , Humans , Female , Pregnancy , Cross-Sectional Studies , United Arab Emirates/epidemiology , Accidents, Traffic/prevention & control
6.
Front Public Health ; 11: 1284288, 2023.
Article in English | MEDLINE | ID: mdl-38074733

ABSTRACT

Background: Sexually transmitted diseases and infections (STDIs) remain a serious public health menace with over 350 million cases each year. Poor knowledge of STDIs has been identified as one of the bottlenecks in their control and prevention. Hence, assessment of knowledge, both general and domain-specific, is key to the prevention and control of these diseases. This study assessed the knowledge of STDIs and identified factors associated with STDI knowledge among university students in the United Arab Emirates (UAE). Methods: This is a cross-sectional study among 778 UAE University students across all colleges. An online data collection tool was used to collect data regarding the participants' demographics and their level of knowledge of STDIs across different domains including general STDI pathogens knowledge (8 items), signs and symptoms (9 items), mode of transmission (5 items), and prevention (5 items). Knowledge was presented both as absolute and percentage scores. Differences in STDI knowledge were statistically assessed using Mann-Whitney U and Chi-squared tests. Logistic regression models were further used to identify factors associated with STDI knowledge. Results: A total of 778 students participated in the study with a median age of 21 years (IQR = 19, 23). The overall median STDI knowledge score of the participants was 7 (out of 27), with some differences within STDI domains-signs & symptoms (1 out of 9), modes of transmission (2 out of 5), general STDI pathogens (2 out of 8), and prevention (1 out of 5). Higher STDI knowledge was significantly associated with being non-Emirati (OR = 1.85, 95% CI = 1.24-2.75), being married (OR = 2.89, 95% CI = 1.50-5.56), residing in emirates other than Abu Dhabi (OR = 1.61, 95% CI = 1.16-2.25), and being a student of health sciences (OR = 4.45, 95% CI = 3.07-6.45). Conclusion: In general, STDI knowledge was low among the students. Having good knowledge of STDIs is essential for their prevention and control. Therefore, there is a need for informed interventions to address the knowledge gap among students, youths, and the general population at large.


Subject(s)
Sexually Transmitted Diseases , Adolescent , Humans , Cross-Sectional Studies , United Arab Emirates/epidemiology , Universities , Surveys and Questionnaires , Sexually Transmitted Diseases/epidemiology , Students
7.
PLoS One ; 18(12): e0295549, 2023.
Article in English | MEDLINE | ID: mdl-38064469

ABSTRACT

BACKGROUND: Low hemoglobin (Hb) level is a leading cause of many adverse pregnancy outcomes. Patterns of changes in Hb levels during pregnancy are not well understood. AIM: This study estimated Hb levels, described its changing patterns across gestational trimesters, and identified factors associated with these changes among pregnant women. MATERIALS AND METHODS: Data from the ongoing maternal and child health cohort study-The Mutaba'ah Study, was used (N = 1,120). KML machine learning algorithm was applied to identify three distinct cluster trajectories of Hb levels between the first and the third trimesters. Descriptive statistics were used to profile the study participants. Multinomial multivariable logistic regression was employed to identify factors associated with change patterns in Hb levels. RESULTS: The three identified clusters-A, B and C-had, respectively, median Hb levels (g/L) of 123, 118, and 104 in the first trimester and 119, 100, and 108 in the third trimester. Cluster 'A' maintained average normal Hb levels in both trimesters. Cluster 'B', on average, experienced a decrease in Hb levels below the normal range during the third trimester. Cluster 'C' showed increased Hb levels in the third trimester but remained, on average, below the normal range in both trimesters. Pregnant women with higher gravida, diabetes mellitus (type 1 or 2), nulliparity or lower level of education were more likely to be in cluster 'B' than the normal cluster 'A'. Pregnant women who reported using iron supplements before pregnancy or those with low levels of education. were more likely to be in cluster 'C' than the normal cluster 'A'. CONCLUSION: The majority of pregnant women experienced low Hb levels during pregnancy. Changes in Hb levels during pregnancy were associated with parity, gravida, use of iron before pregnancy, and the presence of diabetes mellitus (type 1 or 2).


Subject(s)
Diabetes Mellitus, Type 1 , Pregnant Women , Child , Pregnancy , Female , Humans , Cohort Studies , Hemoglobins/analysis , Iron , Parity
8.
Hum Genomics ; 17(1): 98, 2023 Nov 06.
Article in English | MEDLINE | ID: mdl-37932866

ABSTRACT

INTRODUCTION: Genome sequencing has utility, however, it may reveal secondary findings. While Western bioethicists have been occupied with managing secondary findings, specialists' attention in the Arabic countries has not yet been captured. We aim to explore the attitude of the United Arab Emirates (UAE) population toward secondary findings. METHOD: We conducted a cross-sectional study between July and December 2022. The validated questionnaire was administered in English. The questionnaire consists of six sections addressing topics such as demographics, reactions to hypothetical genetic test results, disclosure of mutations to family members, willingness to seek genetic testing, and attitudes toward consanguinity. Chi-squared and Fisher's exact tests were used to investigate associations between categorical variables. RESULTS: We had 343 participants of which the majority were female (67%). About four-fifths (82%) were willing to know the secondary findings, whether the condition has treatment or not. The most likely action to take among the participants was to know the secondary findings, so they can make life choices (61%). CONCLUSION: These results can construct the framework of the bioethics of disclosing secondary findings in the Arab regions.


Subject(s)
Attitude , Bioethics , Humans , Male , Female , Cross-Sectional Studies , United Arab Emirates/epidemiology , Surveys and Questionnaires
9.
Cancer Control ; 30: 10732748231211459, 2023.
Article in English | MEDLINE | ID: mdl-37950611

ABSTRACT

INTRODUCTION: Breast and cervical cancers represent two important causes of cancer-associated deaths in females. Uptake in prevention towards these cancers remains low in the United Arab Emirates. OBJECTIVES: This study aimed to understand the knowledge, attitudes and practices of females residing in the Al Ain city, UAE, towards cervical and breast cancer prevention. METHODS: This cross-sectional survey was conducted with 300 women, aged 30 years and above. The primary outcome measure was cervical and breast cancer prevention knowledge. The knowledge was queried through a number of items, with the resulting aggregate scores categorized into good and low knowledge. Chi-square test was conducted to investigate the association between prevention knowledge and sociodemographic factors. Additional outcomes included attitude towards and uptake of cervical and breast cancer screening. RESULTS: Of the participants surveyed, 36.7% had good knowledge on breast cancer prevention, while 5.3% on cervical cancer prevention. Although the majority of the participants believed that prevention methods could save lives, they reported negative attitudes, considering screening unnecessary and painful. The self-reported screening uptake was 23% and 31.3% for mammography and Pap smear, respectively. CONCLUSIONS: The study reported that the knowledge and uptake of women was low for both breast and cervical cancer prevention. Targeted campaigns not only to increase knowledge but also to resolve misconceptions to change negative attitudes may lead to an increase in uptake.


Subject(s)
Breast Neoplasms , Uterine Cervical Neoplasms , Female , Humans , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/prevention & control , Uterine Cervical Neoplasms/etiology , Cross-Sectional Studies , Health Knowledge, Attitudes, Practice , Breast , Breast Neoplasms/diagnosis , Breast Neoplasms/prevention & control , Breast Neoplasms/complications , Early Detection of Cancer
10.
Hum Genomics ; 17(1): 63, 2023 Jul 15.
Article in English | MEDLINE | ID: mdl-37454085

ABSTRACT

INTRODUCTION: The adoption and implementation of genomic medicine and pharmacogenomics (PGx) in healthcare systems have been very slow and limited worldwide. Major barriers to knowledge translation into clinical practice lie in the level of literacy of the public of genetics and genomics. The aim of this study was to assess the knowledge, attitudes, and perceptions of the United Arab Emirates (UAE) multi-ethnic communities toward genomic medicine and genetic testing. METHOD: A cross-sectional study using validated questionnaires was distributed to the participants. Descriptive statistics were performed, and multivariable logistic regression models were used to identify factors associated with knowledge of genomics. RESULTS: 757 individuals completed the survey. Only 7% of the participants had a good knowledge level in genetics and genomics (95% CI 5.3-9.0%). However, 76.9% of the participants were willing to take a genetic test if their relatives had a genetic disease. In addition, the majority indicated that they would disclose their genetic test results to their spouses (61.5%) and siblings (53.4%). CONCLUSIONS: This study sets the stage for the stakeholders to plan health promotion and educational campaigns to improve the genomic literacy of the community of the UAE as part of their efforts for implementing precision and personalized medicine in the country.


Subject(s)
Genomic Medicine , Health Knowledge, Attitudes, Practice , Humans , United Arab Emirates/epidemiology , Cross-Sectional Studies , Surveys and Questionnaires
11.
Front Public Health ; 11: 1121206, 2023.
Article in English | MEDLINE | ID: mdl-36935714

ABSTRACT

Introduction: The COVID-19 pandemic demonstrated the need for skilled medical practitioners in public health, and outbreak investigations. The College of Medicine and Health Sciences at the United Arab Emirates University (UAEU) introduced a clerkship in public health constituting theoretical and practical sessions to 5th year medical students in 2015. The aim of this study is to explore the satisfaction of the students with the public health clerkship which is crucial for the assessment and reformation of the taught curriculum. Methods: A cross-sectional, post-evaluation analysis was conducted from the period 2015-2022. The evaluation questionnaire was conducted via an online university system. The survey contained 5 themes: pre-course instructions, structure of the clerkship, academic staff, activities, and learning outcomes. Ethics approval was secured from the Social-IRB of the UAEU. We used SPSS version 26 to analyze the data using independent t-test and ANOVA. Results: One hundred and seventy four students (27.4% response rate) participated in the study. Overall, the students had an average satisfaction score of 2.86 out of 4. The majority of the students reported having a good understanding of public health (93.7%), improving their oral presentation skills (91.2%), and developing new skills (87.2%). Furthermore, more than 9 in 10 students (96.1%) reported that the program expanded their knowledge, skills, and confidence. The mass (90.2%) of students agreed that the clerkship content was covered in sufficient depth, majority of the students agreed that they had received enough information about the clerkship before it started (74.6%), majority of the students agreed that the faculty were interested in their personal development (86.1%) The students who completed the clerkship prior to the COVID-19 pandemic had a statistically significant (P = 0.02) higher average rating (72.8%) than students who completed the clerkship during the pandemic (71.1%). Discussion: Medical students at the UAEU were satisfied with the activities and delivery of the public health clerkship and found it rewarding. Conducting needs assessment and proposal writing provided them with the knowledge, skills, and confidence to conduct research in their career. These findings may be useful in helping and support other institutes to plan and develop a clerkship in the public health.


Subject(s)
COVID-19 , Students, Medical , Humans , Public Health , Pandemics , Cross-Sectional Studies , COVID-19/epidemiology
12.
Cell Rep ; 42(3): 112179, 2023 03 28.
Article in English | MEDLINE | ID: mdl-36943868

ABSTRACT

The cGAS-STING pathway is central to the interferon response against DNA viruses. However, recent studies are increasingly demonstrating its role in the restriction of some RNA viruses. Here, we show that the cGAS-STING pathway also contributes to the interferon response against noroviruses, currently the commonest causes of infectious gastroenteritis worldwide. We show a significant reduction in interferon-ß induction and a corresponding increase in viral replication in norovirus-infected cells after deletion of STING, cGAS, or IFI16. Further, we find that immunostimulatory host genome-derived DNA and mitochondrial DNA accumulate in the cytosol of norovirus-infected cells. Lastly, overexpression of the viral NS4 protein is sufficient to drive the accumulation of cytosolic DNA. Together, our data find a role for cGAS, IFI16, and STING in the restriction of noroviruses and show the utility of host genomic DNA as a damage-associated molecular pattern in cells infected with an RNA virus.


Subject(s)
DNA, Mitochondrial , Signal Transduction , DNA, Mitochondrial/genetics , Genomics , Immunity, Innate/genetics , Interferons , Nucleotidyltransferases/metabolism , Signal Transduction/genetics , Membrane Proteins/metabolism
13.
Article in English | MEDLINE | ID: mdl-36293617

ABSTRACT

Occupational illnesses, such as cancer, cause more deaths each year than occupational accidents. Occupational carcinogens include physical, chemical, biological and organizational hazards. In the United Arab Emirates (UAE), migrant workers account for 80% of labor. Being sometimes employed as unskilled workers and more willing to work in demanding jobs, their vulnerability and exposure may be increased. This study aimed to estimate the prevalence of occupational exposure to workplace carcinogens among migrant workers in the UAE. A sample of employees working in construction, cleaning, dry cleaning, mechanic workshops and hair salons were recruited and interviewed. Using OccIDEAS (an online assessment tool), participants were asked questions about their demographics, work history and regular tasks. Exposure to various carcinogens was estimated using the in-built algorithms of OccIDEAS. A sample of 1778 workers was included. The sample consisted of workers from Bangladesh (19.2%), India (31%), Nepal (4.7%), Pakistan (29.9%) and the Philippines (4.8%), with the rest from other nationalities. Overall, the prevalence of probable exposure was considerable, with the highest among drivers (96%) and the lowest among laundry workers (52%). Moderate to high exposure was found to 20 different carcinogens. Self-rated health among those who were exposed to carcinogens was significantly lower than among those not exposed (AOR = 0.783, 95% CI [0.638-0.961]). Exposure to several different carcinogens is relatively common in the UAE among migrant workers. Further strengthening policies and the implementation of tailored interventions are needed to prevent exposure to occupational carcinogens and, consequently, to combat occupational cancer in the UAE.


Subject(s)
Neoplasms , Occupational Diseases , Occupational Exposure , Transients and Migrants , Humans , Carcinogens , Cross-Sectional Studies , United Arab Emirates/epidemiology , Occupational Exposure/analysis , Occupational Diseases/epidemiology , Neoplasms/complications
14.
Viruses ; 14(8)2022 07 23.
Article in English | MEDLINE | ID: mdl-35893676

ABSTRACT

TRIM7 catalyzes the ubiquitination of multiple substrates with unrelated biological functions. This cross-reactivity is at odds with the specificity usually displayed by enzymes, including ubiquitin ligases. Here we show that TRIM7's extreme substrate promiscuity is due to a highly unusual binding mechanism, in which the PRYSPRY domain captures any ligand with a C-terminal helix that terminates in a hydrophobic residue followed by a glutamine. Many of the non-structural proteins found in RNA viruses contain C-terminal glutamines as a result of polyprotein cleavage by 3C protease. This viral processing strategy generates novel substrates for TRIM7 and explains its ability to inhibit Coxsackie virus and norovirus replication. In addition to viral proteins, cellular proteins such as glycogenin have evolved C-termini that make them a TRIM7 substrate. The 'helix-ΦQ' degron motif recognized by TRIM7 is reminiscent of the N-end degron system and is found in ~1% of cellular proteins. These features, together with TRIM7's restricted tissue expression and lack of immune regulation, suggest that viral restriction may not be its physiological function.


Subject(s)
Caliciviridae Infections , Glutamine , Tripartite Motif Proteins , Ubiquitin-Protein Ligases , 3C Viral Proteases , Enterovirus , Humans , Norovirus , Tripartite Motif Proteins/genetics , Ubiquitin-Protein Ligases/metabolism , Viral Proteins/genetics
15.
Preprint in English | bioRxiv | ID: ppbiorxiv-497919

ABSTRACT

TRIM7 catalyses the ubiquitination of multiple substrates with unrelated biological functions. This cross-reactivity is at odds with the specificity usually displayed by enzymes, including ubiquitin ligases. Here we show that TRIM7s extreme substrate promiscuity is due to a highly unusual binding mechanism, in which the PRYSPRY domain captures any ligand with a C-terminal helix that terminates in a hydrophobic residue followed by a glutamine. Many of the non-structural proteins found in RNA viruses contain C-terminal glutamines as a result of polyprotein cleavage by 3C protease. This viral processing strategy generates novel substrates for TRIM7 and explains its ability to inhibit Coxsackie virus and norovirus replication. In addition to viral proteins, cellular proteins such as glycogenin have evolved C-termini that make them a TRIM7 substrate. The helix-{Phi}Q degron motif recognised by TRIM7 is reminiscent of the N-end degron system and is found in [~] 1% of cellular proteins. These features, together with TRIM7s restricted tissue expression and lack of immune regulation suggest that viral restriction may not be its physiological function.

16.
Nat Commun ; 13(1): 751, 2022 02 08.
Article in English | MEDLINE | ID: mdl-35136068

ABSTRACT

Understanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , SARS-CoV-2/genetics , Universities , COVID-19/prevention & control , COVID-19/virology , Contact Tracing , Genome, Viral/genetics , Genomics , Humans , Phylogeny , RNA, Viral/genetics , Risk Factors , SARS-CoV-2/classification , SARS-CoV-2/isolation & purification , Students , United Kingdom/epidemiology , Universities/statistics & numerical data
17.
Wellcome Open Res ; 6: 245, 2021.
Article in English | MEDLINE | ID: mdl-34708158

ABSTRACT

Human noroviruses (HuNoV) are the major cause of viral gastroenteritis worldwide. Similar to other positive-sense single-stranded RNA viruses, norovirus RNA replication requires the formation of a negative strand RNA intermediate. Methods for detecting and quantifying the viral positive or negative sense RNA in infected cells and tissues can be used as important tools in dissecting virus replication. In this study, we have established a sensitive and strand-specific Taqman-based quantitative polymerase chain reaction (qPCR) assay for both genogroups GI and GII HuNoV. This assay shows good reproducibility, has a broad dynamic range and is able to detect a diverse range of isolates. We used tagged primers containing a non-viral sequence for the reverse transcription (RT) reaction and targeted this tag in the succeeding qPCR reaction to achieve strand specificity. The specificity of the assay was confirmed by the detection of specific viral RNA strands in the presence of high levels of the opposing strands, in both RT and qPCR reactions. Finally, we further validated the assay in norovirus replicon-bearing cell lines and norovirus-infected human small intestinal organoids, in the presence or absence of small-molecule inhibitors. Overall, we have established a strand-specific qPCR assay that can be used as a reliable method to understand the molecular details of the human norovirus life cycle.

18.
J Gen Virol ; 102(10)2021 10.
Article in English | MEDLINE | ID: mdl-34698626

ABSTRACT

Human noroviruses (HuNoVs) are increasingly becoming the main cause of transmissible gastroenteritis worldwide, with hundreds of thousands of deaths recorded annually. Yet, decades after their discovery, there is still no effective treatment or vaccine. Efforts aimed at developing vaccines or treatment will benefit from a greater understanding of norovirus-host interactions, including the host response to infection. In this review, we provide a concise overview of the evidence establishing the significance of type I and type III interferon (IFN) responses in the restriction of noroviruses. We also critically examine our current understanding of the molecular mechanisms of IFN induction in norovirus-infected cells, and outline the diverse strategies deployed by noroviruses to supress and/or avoid host IFN responses. It is our hope that this review will facilitate further discussion and increase interest in this area.


Subject(s)
Caliciviridae Infections/immunology , Caliciviridae Infections/virology , Interferons/physiology , Norovirus/immunology , Norovirus/pathogenicity , Animals , Cell Line , Humans , Immune Evasion , Immunity, Innate , Interferons/biosynthesis , Viral Proteins/metabolism , Virus Replication
19.
J Gen Virol ; 102(9)2021 09.
Article in English | MEDLINE | ID: mdl-34491891

ABSTRACT

Murine norovirus (MNV) is widely used as a model for studying norovirus biology. While MNV isolates vary in their pathogenesis, infection of immunocompetent mice mostly results in persistent infection. The ability of a virus to establish a persistent infection is dependent on its ability to subvert or avoid the host immune response. Previously, we described the identification and characterization of virulence factor 1 (VF1) in MNV, and demonstrated its role as an innate immune antagonist. Here, we explore the role of VF1 during persistent MNV infection in an immunocompetent host. Using reverse genetics, we generated MNV-3 viruses carrying a single or a triple termination codon inserted in the VF1 ORF. VF1-deleted MNV-3 replicated to comparable levels to the wildtype virus in tissue culture. Comparative studies between MNV-3 and an acute MNV-1 strain show that MNV-3 VF1 exerts the same functions as MNV-1 VF1, but with reduced potency. C57BL/6 mice infected with VF1-deleted MNV-3 showed significantly reduced replication kinetics during the acute phase of the infection, but viral loads rapidly reached the levels seen in mice infected with wildtype virus after phenotypic restoration of VF1 expression. Infection with an MNV-3 mutant that had three termination codons inserted into VF1, in which reversion was suppressed, resulted in consistently lower replication throughout a 3 month persistent infection in mice, suggesting a role for VF1 in viral fitness in vivo. Our results indicate that VF1 expressed by a persistent strain of MNV also functions to antagonize the innate response to infection. We found that VF1 is not essential for viral persistence, but instead contributes to viral fitness in mice. These data fit with the hypothesis that noroviruses utilize multiple mechanisms to avoid and/or control the host response to infection and that VF1 is just one component of this.


Subject(s)
Caliciviridae Infections/virology , Norovirus/pathogenicity , Viral Proteins/metabolism , Virulence Factors/metabolism , Animals , Apoptosis , Caliciviridae Infections/immunology , Cell Line , Immunity, Innate , Interferon-beta/biosynthesis , Male , Mice , Mice, Inbred C57BL , Norovirus/genetics , Norovirus/physiology , Viral Proteins/genetics , Virulence , Virulence Factors/genetics , Virus Replication , Virus Shedding
20.
Elife ; 102021 08 24.
Article in English | MEDLINE | ID: mdl-34425938

ABSTRACT

SARS-CoV-2 is notable both for its rapid spread, and for the heterogeneity of its patterns of transmission, with multiple published incidences of superspreading behaviour. Here, we applied a novel network reconstruction algorithm to infer patterns of viral transmission occurring between patients and health care workers (HCWs) in the largest clusters of COVID-19 infection identified during the first wave of the epidemic at Cambridge University Hospitals NHS Foundation Trust, UK. Based upon dates of individuals reporting symptoms, recorded individual locations, and viral genome sequence data, we show an uneven pattern of transmission between individuals, with patients being much more likely to be infected by other patients than by HCWs. Further, the data were consistent with a pattern of superspreading, whereby 21% of individuals caused 80% of transmission events. Our study provides a detailed retrospective analysis of nosocomial SARS-CoV-2 transmission, and sheds light on the need for intensive and pervasive infection control procedures.


The COVID-19 pandemic, caused by the SARS-CoV-2 virus, presents a global public health challenge. Hospitals have been at the forefront of this battle, treating large numbers of sick patients over several waves of infection. Finding ways to manage the spread of the virus in hospitals is key to protecting vulnerable patients and workers, while keeping hospitals running, but to generate effective infection control, researchers must understand how SARS-CoV-2 spreads. A range of factors make studying the transmission of SARS-CoV-2 in hospitals tricky. For instance, some people do not present any symptoms, and, amongst those who do, it can be difficult to determine whether they caught the virus in the hospital or somewhere else. However, comparing the genetic information of the SARS-CoV-2 virus from different people in a hospital could allow scientists to understand how it spreads. Samples of the genetic material of SARS-CoV-2 can be obtained by swabbing infected individuals. If the genetic sequences of two samples are very different, it is unlikely that the individuals who provided the samples transmitted the virus to one another. Illingworth, Hamilton et al. used this information, along with other data about how SARS-CoV-2 is transmitted, to develop an algorithm that can determine how the virus spreads from person to person in different hospital wards. To build their algorithm, Illingworth, Hamilton et al. collected SARS-CoV-2 genetic data from patients and staff in a hospital, and combined it with information about how SARS-CoV-2 spreads and how these people moved in the hospital . The algorithm showed that, for the most part, patients were infected by other patients (20 out of 22 cases), while staff were infected equally by patients and staff. By further probing these data, Illingworth, Hamilton et al. revealed that 80% of hospital-acquired infections were caused by a group of just 21% of individuals in the study, identifying a 'superspreader' pattern. These findings may help to inform SARS-CoV-2 infection control measures to reduce spread within hospitals, and could potentially be used to improve infection control in other contexts.


Subject(s)
COVID-19/epidemiology , COVID-19/transmission , Disease Outbreaks/statistics & numerical data , Hospitals/statistics & numerical data , Female , Humans , Male , Middle Aged , Retrospective Studies
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