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Introduction: Canada has endorsed the Joint United National Programme on HIV and AIDS global targets to end the acquired immunodeficiency syndrome (AIDS) epidemic, including reducing new human immunodeficiency virus (HIV) infections to zero, by 2030. Given the effectiveness of pre-exposure prophylaxis (PrEP) to prevent new infections, it is important to measure and report on PrEP utilization to help inform planning for HIV prevention programs and policies. Methods: Annual estimates of persons using PrEP in Canada were generated for 2014–2018 from IQVIA’s geographical prescription monitor dataset. An algorithm was used to distinguish users of tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for PrEP versus treatment or post-exposure prophylaxis. We provide the estimated number of people using PrEP in eight Canadian provinces by sex, age group, prescriber specialty and payment type. Results: The estimated number of PrEP users increased dramatically over the five-year study period, showing a 21-fold increase from 460 in 2014 to 9,657 in 2018. Estimated PrEP prevalence was 416 users per million persons across the eight provinces in 2018. Almost all PrEP users were male. Use increased in both sexes, but increase was greater for males (23-fold) than females (five-fold). Use increased across all provinces, although there were jurisdictional differences in the prevalence of use, age distribution and prescriber types. Conclusion: The PrEP use in Canada increased from 2014 to 2018, demonstrating increased awareness and uptake of its use for preventing HIV transmission. However, there was uneven uptake by age, sex and geography. Since new HIV infections continue to occur in Canada, it will be important to further refine the use of PrEP, as populations at higher risk of HIV infection need to be offered PrEP as part of comprehensive sexual healthcare.

Contexte : Le Canada a approuvé les objectifs mondiaux du Programme commun des Nations Unies sur le VIH et le Sida visant à mettre fin à l’épidémie du syndrome d’immunodéficience acquise (sida), notamment en réduisant à zéro les nouvelles infections par le virus de l’immunodéficience humaine (VIH) d’ici à 2030. Compte tenu de l’efficacité de la prophylaxie pré-exposition (PPrE) pour prévenir les nouvelles infections, il est important de mesurer et de rendre compte de l’utilisation de la PPrE afin de contribuer à la planification des programmes et des politiques de prévention du VIH. Méthodes : Les estimations annuelles des personnes utilisant de la PPrE au Canada ont été générées pour la période de 2014 à 2018 à partir de l’ensemble de données géographiques de surveillance des ordonnances d’IQVIA. On a utilisé un algorithme pour distinguer les utilisateurs de fumarate de ténofovir disoproxil/emtricitabine (TDF/FTC) pour la PPrE de ceux qui l’utilisent dans le cadre d’un traitement ou de la prophylaxie post-exposition. Nous fournissons le nombre estimé de personnes qui utilisent la PPrE dans huit provinces canadiennes par sexe, groupe d’âge, spécialité du médecin prescripteur et type de paiement. Résultats : Le nombre estimé d’utilisateurs de PPrE a augmenté de façon spectaculaire au cours de la période d’étude de cinq ans : il est multiplié par 21, passant de 460 en 2014 à 9 657 en 2018. La prévalence estimée de la PPrE était de 416 utilisateurs par million de personnes dans les huit provinces en 2018. Presque tous les utilisateurs de PPrE étaient des hommes. L’utilisation a augmenté chez les deux sexes, mais l’augmentation a été plus importante chez les hommes (par 23 fois) que chez les femmes (par 5 fois). L’utilisation a augmenté dans toutes les provinces, bien qu’il y ait des différences entre les provinces relativement à la prévalence de l’utilisation, à la répartition par âge et aux types de médecins prescripteurs. Conclusion : L’utilisation de la PPrE au Canada a augmenté entre 2014 et 2018, ce qui témoigne d’une meilleure connaissance et d’une plus grande adhésion à son utilisation pour prévenir la transmission du VIH. Elle est toutefois inégale en fonction de l’âge, du sexe et de la géographie. Puisque les nouvelles infections au VIH continuent de se produire au Canada, il sera important d’affiner l’utilisation de la PPrE, car les populations à risque plus élevé d’infection au VIH doivent se voir offrir la PPrE dans le cadre de soins de santé sexuelle complets.

Abstract Background Protein synthesis is one of the extremely important anabolic pathways in the yeast expression system Pichia pastoris. Codon optimization is a commonly adopted strategy for improved protein expression, although unexpected failures did appear sometimes waiting for further exploration. Recently codon bias has been studied to regulate protein folding and activity in many other organisms. Results Here the codon bias profile of P. pastoris genome was examined first and a direct correlation between codon translation efficiency and usage frequency was identified. By manipulating the codon choices of both endogenous and heterologous signal peptides, secretion abilities of N-terminal signal peptides were shown to be tolerant towards codon changes. Then two gene candidates with different levels of structural disorder were studied, and full-length codon optimization was found to affect their expression profiles differentially. Finally, more evidences were provided to support possible protein conformation change brought by codon optimization in structurally disordered proteins. Conclusion Our results suggest that codon bias regulates gene expression by modulating several factors including transcription and translation efficiency, protein folding and activity. Because of sequences difference, the extent of affection may be gene specific. For some genes, special codon optimization strategy should be adopted to ensure appropriate expression and conformation.

COVID-19 has spread throughout the world; various forecast models have been used to predict the development of the pandemic. The number of new cases from the outbreak to zero has gone through a complete cycle in Hubei, China, on lockdown over coronavirus. So, we created the time series ARIMA models for new cases and new deaths daily during this period. Moreover, these models have been used in Italy, which has the same population conditions and on lockdown as Hubei, in order to predict the epidemic in Italy in the next ten days and provide a theoretical basis for the development of pandemics in some countries in the future.

Tomato yellow leaf curl China virus is a species of the widespread geminiviruses. The infection of Nicotiana benthamiana by Tomato yellow leaf curl China virus (TYLCCNV) causes a reduction in photosynthetic activity, which is part of the viral symptoms. βC1 is a viral factor encoded by the betasatellite DNA (DNAβ) accompanying TYLCCNV. It is a major viral pathogenicity factor of TYLCCNV. To elucidate the effect of βC1 on plants' photosynthesis, we measured the relative chlorophyll (Chl) content and Chl fluorescence in TYLCCNV-infected and βC1 transgenic N. benthamiana plants. The results showed that Chl content is reduced in TYLCCNV A–infected, TYLCCNV A plus DNAβ (TYLCCNV A + β)–infected and βC1 transgenic plants. Further, changes in Chl fluorescence parameters, such as electron transport rate, Fv/Fm, NPQ, and qP, revealed that photosynthetic efficiency is compromised in the aforementioned N. benthamiana plants. The presense of βC1 aggravated the decrease of Chl content and photosynthetic efficiency during viral infection. Additionally, the real-time quantitative PCR analysis of oxygen evolving complex genes in photosystem II, such as PsbO, PsbP, PsbQ, and PsbR, showed a significant reduction of the relative expression of these genes at the late stage of TYLCCNV A + β infection and at the vegetative stage of βC1 transgenic N. benthamiana plants. In summary, this study revealed the pathogenicity of TYLCCNV in photosynthesis and disclosed the effect of βC1 in exacerbating the damage in photosynthesis efficiency by TYLCCNV infection.

Objective To explore the effects of sedation and analgesia with dexmedetomidine and other drugs on the stress response in patients with cerebral hemorrhage after craniotomy hematoma removal and bone flap decompression and insertion of an indwelling endotracheal catheter. Methods A total of 180 patients with cerebral hemorrhage with consciousness disturbance who underwent emergency surgery were included in this study. They were divided into six groups treated with propofol, dexmedetomidine, lidocaine, sufentanil, dezocine, and remifentanil, respectively. Intravenous medication was given after recovery of spontaneous respiration, and stress responses were compared among the group. Results Serum concentrations of norepinephrine, epinephrine, and cortisol and systolic blood pressure were significantly correlated with drug treatment. Serum norepinephrine concentrations differed significantly among the groups, except between the sufentanil and propofol groups. There were significant differences in serum epinephrine concentrations among all groups, and significant differences in serum cortisol concentrations among all groups, except the propofol, dexmedetomidine, and lidocaine groups. Conclusion Dexmedetomidine can reduce the stress response in patients with intracerebral hemorrhage undergoing emergency craniotomy and bone flap decompression, and can reduce adverse events from an indwelling endotracheal catheter 3 hours post-operation.

Background: Neighborhood built environment may profoundly influence children's physical activity (PA) and body weight. This study systematically reviewed scientific evidence regarding the impact of built environment on PA and obesity among children and adolescents in China. Methods: A keyword and reference search was conducted in Active Living Research, Cochrane Library, PubMed, and Web of Science. Studies that met all of the following criteria were included in the review: (1) study designs—experimental studies, observational studies, and qualitative studies; (2) study subjects—Chinese children and/or adolescents aged ≤17 years; (3) exposures—neighborhood built environment; (4) outcomes—PA and/or body weight status; (5) article type—peer-reviewed publications; (6) time window of search—from the inception of an electronicbibliographic database to May 31, 2018; (7) country—China; and (8) language—articles written in English. Results: A total of 20 studies, including 16 cross-sectional studies, 3 longitudinal studies, and 1 descriptive study, met the predetermined selection criteria and were included in the review. A total of 13 studies adopted subjective built environment measures reported by parents and/or children,2 adopted objective measures (e.g., geographical information system, field observations), and 5 adopted both objective and subjective measures. PA behaviors included PA, physical inactivity, sedentary behavior, active/passive commuting from/to school, and park visits. Among the 16 studies that provided some quantitative estimates of the influence of built environment on PA and body weight status, all reported a statistically significant relationship in the expected direction. Availability and accessibility in proximity to greenspaces, parks, recreational facilities, and sidewalks were found to be associated with increased PA levels, reduced sedentary behaviors, and/or active commuting among Chinese childrenand adolescents. In contrast, the absence of bike lanes and living in higher density residential areas were associated with increased likelihood of childhood overweight and obesity. Conclusion: Neighborhood built environment plays an important role in Chinese children's PA engagement and weight outcomes. Building new exercise facilities and enhancing the accessibility of existing facilities hold the potential to enhance PA engagement among Chinese children and adolescents. In addition, urban designs that incorporate sidewalks, bike lanes, walking paths, less motorized traffic, and lower residential density are likely to promote PA and prevent childhood obesity in China. Keywords: Body weight, Chinese, Exercise, Literature review, Local environment, Neighborhood environment, Physical environment

This prospective cohort study designed to assess the effect of folic acid supplementation in pregnancy on the risk of preeclampsia (PE) took place in Ottawa, ON and Kingston, ON, Canada, from September 1, 2002 to August 31, 2008. Pregnant women, less than 20 weeks gestational age were recruited and delivered in the Ottawa region and the Kingston General Hospital. Demographic characteristics of the study participants and the patterns of supplementation of folic acid were described and occurrence of PE between women with folic acid supplementation during pregnancy and women without were compared. Multiple logistic regression was used in the estimation of the independent effect of supplementation of folic acid. Additional analyses assessing the effect of low RBC and serum folate and dose-response relationship were performed. Analyses were performed in all study participants, and then in high risk and low risk sub-groups, respectively. A total of 7,669 participants were included in the final analysis. Ninety five percent of the study participants were taking folic acid supplementation in early second trimester. The rate of PE was lower in the supplementation group than in the no supplementation group, and the difference was statistically significant in high risk women. Similar patterns of associations were observed in analysis by RBC and serum folate levels and in dose-response analysis. Folic acid supplementation in pregnancy may reduce PE risk in pregnant women, especially in those women with increased risk of developing PE.

OBJECTIVE: To evaluate the correlation of total lymphocyte count (TLC) and CD4 cell count and the suitability of TLC as a surrogate marker for CD4 cell count of HIV-infected patients in China. METHODS: Usefulness of TLC as a surrogate marker for a CD4 cell count

Most plant and animal microRNAs (miRNAs) are transcribed by RNA polymerase II. We previously discovered miRNA-like small RNAs (milRNAs) in the filamentous fungus Neurospora crassa and uncovered at least four different pathways for milRNA production. To understand the evolutionary origin of milRNAs, we determined the roles of polymerases II and III (Pol II and Pol III) in milRNA transcription. Our results show that Pol III is responsible for the transcription of the major milRNAs produced in this organism. The inhibition of Pol III activity by an inhibitor or by gene silencing abolishes the production of most abundant milRNAs and pri-milRNAs. In addition, Pol III associates with these milRNA producing loci. Even though silencing of Pol II does not affect the synthesis of the most abundant milRNAs, Pol II or both Pol II and Pol III are associated with some milRNA-producing loci, suggesting a regulatory interaction between the two polymerases for some milRNA transcription. Furthermore, we show that one of the Pol III-transcribed milRNAs is derived from a tRNA precursor, and its biogenesis requires RNase Z, which cleaves the tRNA moiety to generate pre-milRNA. Our study identifies the transcriptional machinery responsible for the synthesis of fungal milRNAs and sheds light on the evolutionary origin of eukaryotic small RNAs.

The production of aberrant RNA (aRNA) is the initial step in several RNAi pathways. How aRNA is produced and specifically recognized by RNA-dependent RNA polymerases (RdRPs) to generate double-stranded RNA (dsRNA) is not clear. We previously showed that in the filamentous fungus Neurospora, the RdRP QDE-1 is required for rDNA-specific aRNA production, suggesting that QDE-1 may be important in aRNA synthesis. Here we show that a recombinant QDE-1 is both an RdRP and a DNA-dependent RNA polymerase (DdRP). Its DdRP activity is much more robust than the RdRP activity and occurs on ssDNA but not dsDNA templates. We further show that Replication Protein A (RPA), a single-stranded DNA-binding complex that interacts with QDE-1, is essential for aRNA production and gene silencing. In vitro reconstitution assays demonstrate that QDE-1 can produce dsRNA from ssDNA, a process that is strongly promoted by RPA. Furthermore, the interaction between QDE-1 and RPA requires the RecQ DNA helicase QDE-3, a homolog of the human Werner/Bloom Syndrome proteins. Together, these results suggest a novel small RNA biogenesis pathway in Neurospora and a new mechanism for the production of aRNA and dsRNA in RNAi pathways.

Background: Gay or bisexual (GB) and other men who have sex with men (MSM) are disproportionately affected by human immunodeficiency virus (HIV) globally and domestically in Canada. Reliable and recent population size estimates are necessary to allocate resources to meet prevention needs and for modelling the HIV epidemic. However, previous direct estimates did not account for GB men who would not reveal their sexual identity to a government survey, nor MSM not identifying as GB. The objective of this study was to develop two national population size estimates of gay, bisexual and other men who have sex with men (gbMSM) in 2020. First, GB men based on identity, regardless of sexual experience, and MSM who do not identify as GB but reported anal sex with a man in the past 1–5 years (“Identity-or-Behaviour” estimate). Second, an estimate of gbMSM who reported past 6–12 months anal sex with a man (“Behaviour-only” estimate). Methods: Estimates for males aged 15 years and older were drawn from Statistics Canada’s population size estimates, the Canadian Community Health Survey and the Community-Based Research Centre’s Sex Now Survey. Estimated proportions of GB identity, those not likely to disclose GB identity and MSM who do not identify as GB but who reported past 1–5 years anal sex were applied. Past 6–12 months anal sex history was subsequently used to limit estimates to those sexually active anally. Results: It was estimated that 3.5% of the male population in Canada aged 15 years and older identified as GB. Of GB males, 86.5% were likely to disclose their sexual identity to a government survey. A further 0.1% of non-GB identified males reported past year anal sex with a man. The national Identity-or-Behaviour gbMSM population size in 2020 was estimated at 669,613 people, equivalent to 4.3% of the Canadian male population aged 15 years and older. The estimate of Behaviour-only gbMSM was 412,186, representing 2.6% of the Canadian male population aged 15 years and older. Conclusion: Using data from multiple sources, a model applied to estimate the population size of gbMSM, accounting for populations previously not included in prior estimates, has been described. [ABSTRACT FROM AUTHOR]

Background: Estimates of the number of hepatitis C virus (HCV) infections are important for monitoring efforts aimed at preventing disease transmission, especially following the introduction of a highly effective treatment. This report provides updated estimates of HCV incidence, prevalence, undiagnosed proportion and treatment in Canada. Methods: A combination of back calculation modelling and a modified version of the workbook method were used to estimate the incidence and prevalence of anti-HCV positive persons, the prevalence of chronic HCV infection and the undiagnosed proportion. The number of people treated for chronic HCV was estimated using administrative pharmaceutical data. Results: An estimated 9,470 new infections occurred in 2019, corresponding to an incidence rate of 25 per 100,000 population, a 7.7% decrease since 2015. The estimated prevalence of anti-HCV antibodies in the Canadian population was 1.03% (plausible range: 0.83%-1.38%), and the estimated prevalence of chronic HCV was 0.54% (plausible range: 0.40%-0.79%). The overall proportion of anti-HCV positive persons who were undiagnosed was estimated at 24% of all infections, with individuals born between 1945 and 1975 being the priority population the most likely to be undiagnosed. An estimated 74,500 people with chronic HCV have been treated since the introduction of direct-acting antivirals in 2014. Conclusion: Estimates of HCV incidence and prevalence are key metrics to guide interventions and resource allocation. While our estimates show that HCV incidence has decreased in Canada in recent years and treatment of chronic HCV has continued to increase, ongoing efforts are required to reduce the burden of HCV in Canada. [ABSTRACT FROM AUTHOR]

Introduction: : Canada has endorsed the Joint United National Programme on HIV and AIDS global targets to end the acquired immunodeficiency syndrome (AIDS) epidemic, including reducing new human immunodeficiency virus (HIV) infections to zero, by 2030. Given the effectiveness of pre-exposure prophylaxis (PrEP) to prevent new infections, it is important to measure and report on PrEP utilization to help inform planning for HIV prevention programs and policies.Methods: : Annual estimates of persons using PrEP in Canada were generated for 2014-2018 from IQVIA's geographical prescription monitor dataset. An algorithm was used to distinguish users of tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for PrEP versus treatment or post-exposure prophylaxis. We provide the estimated number of people using PrEP in eight Canadian provinces by sex, age group, prescriber specialty and payment type.Results: : The estimated number of PrEP users increased dramatically over the five-year study period, showing a 21-fold increase from 460 in 2014 to 9,657 in 2018. Estimated PrEP prevalence was 416 users per million persons across the eight provinces in 2018. Almost all PrEP users were male. Use increased in both sexes, but increase was greater for males (23-fold) than females (five-fold). Use increased across all provinces, although there were jurisdictional differences in the prevalence of use, age distribution and prescriber types.Conclusion: : The PrEP use in Canada increased from 2014 to 2018, demonstrating increased awareness and uptake of its use for preventing HIV transmission. However, there was uneven uptake by age, sex and geography. Since new HIV infections continue to occur in Canada, it will be important to further refine the use of PrEP, as populations at higher risk of HIV infection need to be offered PrEP as part of comprehensive sexual healthcare. [ABSTRACT FROM AUTHOR]