The Landscape of L1 Retrotransposons in the Human Genome Is Shaped by Pre-insertion Sequence Biases and Post-insertion Selection.

L1 retrotransposons are transposable elements and major contributors of genetic variation in humans. Where L1 integrates into the genome can directly impact human evolution and disease. Here, we experimentally induced L1 retrotransposition in cells and mapped integration sites at nucleotide resolution. At local scales, L1 integration is mostly restricted by genome sequence biases and the specificity of the L1 machinery. At regional scales, L1 shows a broad capacity for integration into all chromatin states, in contrast to other known mobile genetic elements. However, integration is influenced by the replication timing of target regions, suggesting a link to host DNA replication. The distribution of new L1 integrations differs from those of preexisting L1 copies, which are significantly reshaped by natural selection. Our findings reveal that the L1 machinery has evolved to efficiently target all genomic regions and underline a predominant role for post-integrative processes on the distribution of endogenous L1 elements.

Alkaline-sensitive two-pore domain potassium channels form functional heteromers in pancreatic ß-cells.

Two-pore domain K+ channels (K2P channels), active as dimers, produce inhibitory currents regulated by a variety of stimuli. Among them, TWIK1-related alkalinization-activated K+ channel 1 (TALK1), TWIK1-related alkalinization-activated K+ channel 2 (TALK2), and TWIK1-related acid-sensitive K+ channel 2 (TASK2) form a subfamily of structurally related K2P channels stimulated by extracellular alkalosis. The human genes encoding these proteins are clustered at chromosomal region 6p21 and coexpressed in multiple tissues, including the pancreas. The question whether these channels form functional heteromers remained open. By analyzing single-cell transcriptomic data, we show that these channels are coexpressed in insulin-secreting pancreatic ß-cells. Using in situ proximity ligation assay and electrophysiology, we show that they form functional heterodimers both upon heterologous expression and under native conditions in human pancreatic ß-cells. We demonstrate that heteromerization of TALK2 with TALK1 or with TASK2 endows TALK2 with sensitivity to extracellular alkalosis in the physiological range. We further show that the association of TASK2 with TALK1 and TALK2 increases their unitary conductance. These results provide a new example of heteromerization in the K2P channel family expanding the range of the potential physiological and pathophysiological roles of TALK1/TALK2/TASK2 channels, not only in insulin-secreting cells but also in the many other tissues in which they are coexpressed.

Determinants of parental vaccine hesitancy in Canada: results from the 2017 Childhood National Immunization Coverage Survey.

BACKGROUND: In 2019, the World Health Organization (WHO) designated vaccine hesitancy as one of the ten leading threats to global health. Vaccine hesitancy exists when vaccination services are available and accessible, but vaccine uptake is lower than anticipated. It is often attributed to lack of trust in vaccine safety and effectiveness, or low level of concern about the risk of many vaccine-preventable diseases. This study aimed to examine the sociodemographic factors associated with parental vaccine hesitancy and vaccine refusal in Canada using data from the 2017 Childhood National Immunization Coverage Survey (CNICS). METHOD: The 2017 CNICS was a cross-sectional and nationally representative survey to estimate national vaccine uptake and to collect information about parents' Knowledge, Attitudes and Beliefs (KAB) regarding vaccination. Using the KAB questions, parental vaccine hesitancy (i.e., parental hesitation, delay or refusal of at least one recommended vaccination) and refusal (i.e., unvaccinated children) by sociodemographic factors was estimated using weighted prevalence proportions. A multinomial logistic regression model was fitted to examine associations between parental vaccine hesitancy or refusal and sociodemographic factors among parents of two-year-old children in Canada. Adjusted odds ratios (aOR) of being vaccine-hesitant or vaccine-refusing versus being non-vaccine-hesitant were generated. RESULTS: Both unadjusted and adjusted logistic regressions models showed that parents with lower household income (aOR 1.7, 95% CI 1.2-2.5), and those with a higher number of children in the household (aOR 2.2, 95% CI 1.4-3.5) had higher vaccine hesitancy. Conversely, lower vaccine hesitancy was observed among non-immigrant parents (aOR 0.4, 95% CI 0.3-0.6). In addition, lower household income (aOR 4.0, 95% CI 1.3-12.9), and higher number of children in the household (aOR 6.9, 95% CI 2.1-22.9) were significantly associated with parental vaccine refusal. Regional variations were also observed. CONCLUSION: Several sociodemographic determinants are associated with parental vaccine hesitancy and refusal. The findings of the study could help public health officials and policymakers to develop and implement targeted interventions to improve childhood vaccination programs.

Pertussis Non-Vaccination During Pregnancy Despite Advice From Prenatal Care Providers.

OBJECTIVE: The purpose of this study was to measure the proportion of non-vaccination for pertussis in mothers in Canada who had been advised by their prenatal care provider to get vaccinated, and to identify sociodemographic factors and beliefs associated with non-vaccination. METHODS: The Survey on Vaccination during Pregnancy (part of childhood National Immunization Coverage Survey) included biological mothers of children born from September 2018 to March 2019. This analysis was restricted to 2657 mothers who had been advised by their prenatal care provider to get vaccinated against pertussis during pregnancy and knew whether or not they had been vaccinated. RESULTS: Of those who had been advised to get vaccinated against pertussis, 21% were not. This rate varied across provinces and territories, ranging from 9% in Prince Edward Island to 32% in Newfoundland and Labrador. Factors independently associated with pertussis non-vaccination included lower household income, having had past live births, and having received prenatal care from an obstetrician-gynecologist or a midwife compared to a family doctor. The risk of pertussis non-vaccination despite prenatal care advice was higher for those who disagreed that the baby would be at greater risk of pertussis if the mother did not get vaccinated. It was also higher for those who disagreed with statements regarding perceived benefits of vaccination. Conversely, disagreement with statements on perceived barriers was negatively associated with pertussis non-vaccination. CONCLUSION: These findings highlight the underlying factors associated with non-vaccination against pertussis despite prenatal care provider recommendation. Some inaccurate beliefs about pertussis and vaccination during pregnancy persist, leading to non-vaccination.

Detection, discrimination and quantification of amphetamine, cathinone and nor-ephedrine regioisomers using benchtop 1 H and 19 F nuclear magnetic resonance spectroscopy.

Amphetamine and cathinone derivatives are abused recreationally due to the sense of euphoria they provide to the user. Methodologies for the rapid detection of the drug derivative present in a seized sample, or an indication of the drug class, are beneficial to law enforcement and healthcare providers. Identifying the drug class is prudent because derivatisation of these drugs, to produce regioisomers, for example, occurs frequently to circumvent global and local drug laws. Thus, newly encountered derivatives might not be present in a spectral library. Employment of benchtop nuclear magnetic resonance (NMR) could be used to provide rapid analysis of seized samples as well as identifying the class of drug present. Discrimination of individual amphetamine-, methcathinone-, N-ethylcathinone and nor-ephedrine-derived fluorinated and methylated regioisomers is achieved herein using qualitative automated 1 H NMR analysis and compared to gas chromatography-mass spectrometry (GC-MS) data. Two seized drug samples, SS1 and SS2, were identified to contain 4-fluoroamphetamine by 1 H NMR (match score median = 0.9933) and GC-MS (RRt = 5.42-5.43 min). The amount of 4-fluoroamphetamine present was 42.8%-43.4% w/w and 48.7%-49.2% w/w for SS1 and SS2, respectively, from quantitative 19 F NMR analysis, which is in agreement with the amount determined by GC-MS (39.9%-41.4% w/w and 49.0%-49.3% w/w). The total time for the qualitative 1 H NMR and quantitative 19 F NMR analysis is ~10 min. This contrasts to ~40 min for the GC-MS method. The NMR method also benefits from minimal sample preparation. Thus, benchtop NMR affords rapid, and discriminatory, analysis of the drug present in a seized sample.

Measuring inequalities in COVID-19 vaccination uptake and intent: results from the Canadian Community Health Survey 2021.

BACKGROUND: By July 2021, Canada had received enough COVID-19 vaccines to fully vaccinate every eligible Canadian. However, despite the availability of vaccines, some eligible individuals remain unvaccinated. Differences in vaccination uptake can be driven by health inequalities which have been exacerbated and amplified by the pandemic. This study aims to assess inequalities in COVID-19 vaccination uptake and intent in adults 18 years or older across Canada by identifying sociodemographic factors associated with non-vaccination and low vaccination intent using data drawn from the June to August 2021 Canadian Community Health Survey (CCHS). METHODS: The CCHS is an annual cross-sectional and nationally representative survey conducted by Statistics Canada, which collects health-related information. Since September 2020, questions about the COVID-19 pandemic are asked. Adjusted logistic regression models were fitted to examine associations between vaccination uptake or intent and sociodemographic and health related variables. Region, age, gender, level of education, Indigenous status, visible minority status, perceived health status, and having a regular healthcare provider were considered as predictors, among other factors. RESULTS: The analysis included 9,509 respondents. The proportion of unvaccinated was 11%. Non-vaccination was associated with less than university education (aOR up to 3.5, 95% CI 2.1-6.1), living with children under 12 years old (aOR 1.6, 95% CI 1.1-2.4), not having a regular healthcare provider (aOR 1.6, 95% CI 1.1-2.2), and poor self-perceived health (aOR 1.8, 95% CI 1.3-2.4). Only 5% of the population had low intention to get vaccinated. Being unlikely to get vaccinated was associated with the Prairies region (aOR 2.2, 95% CI 1.2-4.1), younger age groups (aOR up to 4.0, 95% CI 1.3-12.3), less than university education (aOR up to 3.8, 95% CI 1.9-7.6), not being part of a visible minority group (aOR 3.0, 95% CI 1.4-6.4), living with children under 12 years old (aOR 1.8, 95% CI 1.1-2.9), unattached individuals (aOR 2.6, 95% CI 1.1-6.1), and poor self-perceived health (aOR 2.0, 95% CI 1.3-2.9). CONCLUSIONS: Disparities were observed in vaccination uptake and intent among various sociodemographic groups. Awareness of inequalities in COVID-19 vaccination uptake and intent is needed to determine the vaccination barriers to address in vaccination promotion strategies.

Pertussis Vaccination in Canadian Pregnant Women, 2018-2019.

OBJECTIVE: This study was undertaken to measure the uptake of pertussis vaccination during pregnancy in Canada and to identify sociodemographic factors associated with non-vaccination. METHODS: A total of 5091 biological mothers of children born between September 2, 2018, and March 1, 2019, were interviewed about pertussis vaccination during their pregnancy. RESULTS: Among 4607 mothers who recalled whether they had been vaccinated for pertussis, 43% had been vaccinated and 57% had not. The main reason given by mothers for not having been vaccinated was not being aware that pertussis vaccination was recommended. Factors independently associated with non-vaccination were being born outside Canada, lower household income, living in a province or territory where pertussis vaccination was not provided free of charge, having had previous live births, and having received maternity care from a midwife. CONCLUSION: Advice from the maternity care provider is an important driver of pertussis vaccination during pregnancy.

DNA helicase RecQ1 regulates mutually exclusive expression of virulence genes in Plasmodium falciparum via heterochromatin alteration.

The Plasmodium falciparum var gene family encodes ∼60 surface antigens by which parasites escape the host immune responses via clonal expression of var genes. However, the mechanism controlling this mutual exclusivity, associated with alterations in chromatin assembly, is not understood. Here, we determined how expression of the var gene family is regulated by two RecQ DNA helicase family members, PfRecQ1 and PfWRN, in P. falciparum Through genetic manipulation, we found that the complete var repertoire was silenced on PfRecQ1 knockout, whereas their expression did not show noticeable changes when PfWRN was knocked out. More important, mutually exclusive expression of var genes could be rescued by complementation of PfRecQ1. In addition, knocking out either of these two helicase genes changed the perinuclear cluster distribution of subtelomeres and subtelomeric var genes. Whereas deletion of PfRecQ1 increased the heterochromatin mark trimethylated (H3K9me3) at the transcription start site (TSS) of the var gene upsC1, that deletion had no effect on the global distribution of H3K9me3 over gene bodies, including those for the var genes. ChIP-seq assay showed that PfRecQ1 was enriched globally at the TSSs of all genes, whereas PfWRN-enriched regions occurred at the gene bodies of the var gene family, but not of other genes or at TSSs of all genes. On PfRecQ1 deletion, the upsC1 var gene moved from the active perinuclear transcription region to a silenced region of the upsC type. These findings imply that PfRecQ1, but not PfWRN, is essential for maintaining the clonal expression of var genes.

Sociodemographic Disparities in COVID-19 Vaccine Uptake and Vaccination Intent in Canada.

Introduction: This study's objective was to examine sociodemographic disparities in COVID-19 vaccine uptake and vaccination intent in the Canadian provinces by identifying factors associated with vaccine uptake in seniors prioritized for vaccination at the time of the survey and vaccination intent in all adults. Data and methods: A cross-sectional survey of Canadian adults was conducted in all provinces from mid-April to mid-May 2021. In addition to sociodemographic characteristics, respondents (n=10,678) provided information on their COVID-19 vaccination status or their intent to get vaccinated. Logistic regression models were fitted using sociodemographic factors as explanatory variables and vaccination status (unvaccinated vs at least one dose) or vaccination intent (unlikely versus likely or already vaccinated) as outcomes. To account for vaccine prioritization groups, multiple regression models were adjusted for province of residence, age, Indigenous identity and health care worker status. Results: Seniors with a lower household income (less than $60,000) and those living in smaller communities (fewer than 100,000 inhabitants) had higher odds of being unvaccinated. Among Canadian adults, the odds of being unlikely to get vaccinated were higher for males (adjusted odds ratio [AOR] 1.3), individuals younger than 60 (AOR between 3.3 and 5.1), non-health care workers (AOR 3.3), those with less than a high school education (AOR 3.4) or a household income of less than $30,000 (AOR 2.7) and individuals who do not identify as South Asian, Chinese, Black, Filipino, Arab, Latin American, Southeast Asian, West Asian, Korean or Japanese (AOR 1.7). Interpretation: COVID-19 vaccine uptake (80%) and vaccination intent (95%) were high among Canadians; however, relative disparities were observed among specific groups. Continued efforts targeted toward these groups are essential in reducing potential inequity in access or service provision.

Long non-coding RNA exploration for mesenchymal stem cell characterisation.

BACKGROUND: The development of RNA sequencing (RNAseq) and the corresponding emergence of public datasets have created new avenues of transcriptional marker search. The long non-coding RNAs (lncRNAs) constitute an emerging class of transcripts with a potential for high tissue specificity and function. Therefore, we tested the biomarker potential of lncRNAs on Mesenchymal Stem Cells (MSCs), a complex type of adult multipotent stem cells of diverse tissue origins, that is frequently used in clinics but which is lacking extensive characterization. RESULTS: We developed a dedicated bioinformatics pipeline for the purpose of building a cell-specific catalogue of unannotated lncRNAs. The pipeline performs ab initio transcript identification, pseudoalignment and uses new methodologies such as a specific k-mer approach for naive quantification of expression in numerous RNAseq data. We next applied it on MSCs, and our pipeline was able to highlight novel lncRNAs with high cell specificity. Furthermore, with original and efficient approaches for functional prediction, we demonstrated that each candidate represents one specific state of MSCs biology. CONCLUSIONS: We showed that our approach can be employed to harness lncRNAs as cell markers. More specifically, our results suggest different candidates as potential actors in MSCs biology and propose promising directions for future experimental investigations.

Hyperpolarisation of Mirfentanil by SABRE in the Presence of Heroin.

Mirfentanil, a fentanyl derivative that is a µ-opioid partial agonist, is hyperpolarised via Signal Amplification By Reversible Exchange (SABRE), a para-hydrogen-based technique. [Ir(IMes)(COD)Cl] (IMes=1,3-bis(2,4,6-trimethylphenyl)imidazole-2-ylidene, COD=cyclooctadiene) was employed as the polarisation transfer catalyst. Following polarisation transfer at 6.5 mT, the pyrazine-protons were enhanced by 78-fold (polarisation, P=0.04 %). The complex [Ir(IMes)(H)2 (mirfentanil)2 (MeOH)]+ is proposed to form based on the observation of two hydrides at δ -22.9 (trans to mirfentanil) and -24.7 (trans to methanol). In a mixture of mirfentanil and heroin, the former could be detected using SABRE at concentrations less than 1 % w/w. At the lowest concentration analyzed, the amount of mirfentanil present was 0.18 mg (812 µM) and produced a signal enhancement of -867-fold (P=0.42 %). following polarisation transfer at 6.5 mT.

Socioeconomic status differences in parental immunization attitudes and child immunization in Canada: Findings from the 2013 Childhood National Immunization Coverage Survey (CNICS).

Childhood vaccination efforts in Canada have been negatively impacted by parents' vaccine hesitancy based on their knowledge, attitudes, and beliefs (KAB) about vaccinations. Less understood is the extent to which child vaccination receipt and KAB vary by parents' socioeconomic status (SES). Analyzing different age groups of children and vaccinations, we examine the extent to which (a) family SES (parent education, household income) is a determinant of Canadian parents' vaccination KAB and child vaccination receipt, and (b) whether SES was indirectly associated with receipt via KAB. In 2017, we analyzed 2013 Childhood National Immunization Coverage Survey (CNICS) data. We estimated models for parental KAB and child vaccination receipt for measles, mumps, and rubella (MMR) at age 2 (n = 3620); diphtheria, pertussis, and tetanus (DPT) at age 7 (n = 3465); and human papillomavirus (HPV) at ages 12-14 (n = 5213 females). SES is inconsistently associated with KAB and vaccine receipt across the three age groups. SES differences in KAB mostly center on vaccine-specific side effect and safety concerns, with lower education and income levels associated with higher odds of being concerned. Non-receipt of minimum age-specific vaccination dosages was associated with concerns about vaccine effectiveness (DPT, HPV) and side effects (MMR, HPV) and lower perceived importance of immunizing a child (MMR, HPV). KAB mediation was mostly limited to SES patterns in MMR. We discuss the implications of these findings for designing general and population-specific vaccination education strategies and future studies of KAB and undervaccination.

Determinants of non-vaccination against seasonal influenza.

BACKGROUND: In Canada, vaccine coverage for seasonal influenza remains below targets. Few studies have sought to determine the sociodemographic factors associated with non-vaccination using a Canada-wide survey. This study aims to identify the determinants of, and the reasons for, non-vaccination. DATA AND METHODS: Data from the 2013/2014 Canadian Community Health Survey (CCHS) were used. Respondents were divided into three groups: adults aged 18 to 64 years with a chronic medical condition (CMC), adults in the same age group with no CMC, and adults aged 65 years and older. Logistic regressions were used to measure the association between sociodemographic factors and non-vaccination. RESULTS: Among adults aged 65 years and older, the proportion of non-vaccinated persons was 36.2%. This proportion was higher among adults aged 18 to 64 years with a CMC and those with no CMC (62.2% and 77.8%, respectively). Factors independently associated with non-vaccination in all groups included being young, having a lower level of education, and not having a family doctor. Among adults aged 65 years and older and 18 to 64 years with a CMC, excellent self-perceived health was also associated with non-vaccination. The belief that the vaccine is not necessary was the most common reason for non-vaccination. DISCUSSION: Too few Canadians get the influenza vaccine. The main reasons for not getting vaccinated have more to do with personal decision than barriers to access. This illustrates the ongoing need to inform the public about the importance of the vaccine and the risks associated with influenza.

U6 snRNA Pseudogenes: Markers of Retrotransposition Dynamics in Mammals.

Transposable elements comprise more than 45% of the human genome and long interspersed nuclear element 1 (LINE-1 or L1) is the only autonomous mobile element remaining active. Since its identification, it has been proposed that L1 contributes to the mobilization and amplification of other cellular RNAs and more recently, experimental demonstrations of this function has been described for many transcripts such as Alu, a nonautonomous mobile element, cellular mRNAs, or small noncoding RNAs. Detailed examination of the mobilization of various cellular RNAs revealed distinct pathways by which they could be recruited during retrotransposition; template choice or template switching. Here, by analyzing genomic structures and retrotransposition signatures associated with small nuclear RNA (snRNA) sequences, we identified distinct recruiting steps during the L1 retrotransposition cycle for the formation of snRNA-processed pseudogenes. Interestingly, some of the identified recruiting steps take place in the nucleus. Moreover, after comparison to other vertebrate genomes, we established that snRNA amplification by template switching is common to many LINE families from several LINE clades. Finally, we suggest that U6 snRNA copies can serve as markers of L1 retrotransposition dynamics in mammalian genomes.

Differences in perinatal and infant mortality in high-income countries: artifacts of birth registration or evidence of true differences?

BACKGROUND: Variation in birth registration criteria may compromise international comparisons of fetal and infant mortality. We examined the effect of birth registration practices on fetal and infant mortality rates to determine whether observed differences in perinatal and infant mortality rates were artifacts of birth registration or reflected true differences in health status. METHODS: A retrospective population-based cohort study was done using data from Canada, United States, Denmark, Finland, Iceland, Norway, and Sweden from 1995-2005. Main outcome measures included live births by gestational age and birth weight; gestational age-and birth weight-specific stillbirth rates; neonatal, post-neonatal, and cause-specific infant mortality. RESULTS: Proportion of live births <22 weeks varied substantially: Sweden (not reported), Iceland (0.00%), Finland (0.001%), Denmark (0.01%), Norway (0.02%), Canada (0.07%) and United States (0.08%). At 22-23 weeks, neonatal mortality rates were highest in Canada (892.2 per 1000 live births), Denmark (879.3) and Iceland (1000.0), moderately high in the United States (724.1), Finland (794.3) and Norway (739.0) and low in Sweden (561.2). Stillbirth:live birth ratios at 22-23 weeks were significantly lower in the United States (79.2 stillbirths per 100 live births) and Finland (90.8) than in Canada (112.1), Iceland (176.2) and Norway (173.9). Crude neonatal mortality rates were 83% higher in Canada and 96% higher in the United States than Finland. Neonatal mortality rates among live births ≥ 28 weeks were lower in Canada and United States compared with Finland. Post-neonatal mortality rates were higher in Canada and United States than in Nordic countries. CONCLUSIONS: Live birth frequencies and stillbirth and neonatal mortality patterns at the borderline of viability are likely due to differences in birth registration practices, although true differences in maternal, fetal and infant health cannot be ruled out. This study emphasises the need for further standardisations, in order to enhance the relevance of international comparisons of infant mortality.

Smoking cessation during pregnancy and relapse after childbirth in Canada.

OBJECTIVE: This analysis was undertaken to determine the rates and determinants of smoking cessation during pregnancy and smoking relapse after childbirth in Canada. METHODS: We used data from the Maternity Experiences Survey, a cross-sectional study of mothers who gave birth to a singleton baby in Canada in 2006. A total of 1586 mothers who smoked occasionally or daily before pregnancy were included in the analysis. RESULTS: The rate of smoking cessation during pregnancy was 53.0% (95% CI 50.3% to 55.7%). Higher pre-pregnancy smoking frequency, Inuit origin, being aged ≥ 35 years, lower education, not attending prenatal classes, lack of social support, stress before or during pregnancy, and living with a smoker were independently associated with higher risk of continued smoking, while First Nations (off-reserve) origin was associated with a lower risk. Among those who had quit smoking, 47.1% (95% CI 43.5% to 50.6%) relapsed postpartum. Living with a smoker, not having breastfed, and having stopped breastfeeding were independently associated with a higher risk of relapse. CONCLUSION: This study highlights the need to tailor smoking cessation and prevention interventions for some high-risk groups of women.

Objectif : Cette analyse a été menée pour déterminer les taux et les déterminants de l'arrêt tabagique pendant la grossesse et de la rechute post-partum au Canada. Méthodes : Nous avons utilisé les données de l'Enquête sur l'expérience de la maternité, soit une étude transversale sur des mères ayant accouché à la suite d'une grossesse simple au Canada en 2006. En tout, 1 586 mères ayant fumé occasionnellement ou quotidiennement avant la grossesse ont été incluses dans l'analyse. Résultats : Le taux d'arrêt tabagique pendant la grossesse était de 53,0 % (IC à 95 %, 50,3 % - 55,7 %). Une consommation de cigarettes plus élevée avant la grossesse, être d'origine inuite, être âgée de 35 ans ou plus, être moins scolarisée, la non-participation à des cours prénataux, le manque de soutien social, le stress avant ou pendant la grossesse et la cohabitation avec un fumeur étaient associés de façon indépendante à un risque accru de poursuite du tabagisme, tandis que le fait d'être issue des Premières Nations (hors-réserve) était associé à un risque moindre. Parmi les mères qui avaient cessé de fumer, 47,1 % (IC à 95 %, 43,5 % - 50,6 %) ont recommencé à fumer après l'accouchement. La cohabitation avec un fumeur, ne pas avoir allaité et avoir cessé d'allaiter étaient associés de façon indépendante à un risque accru de rechute. Conclusion : Cette étude souligne la nécessité d'adapter les interventions d'abandon et de prévention du tabagisme aux groupes de femmes exposées à des risques élevés.

Stillbirth and infant mortality in Aboriginal communities in Quebec.

BACKGROUND: Infant mortality and stillbirth rates among Aboriginal people are higher than in the rest of Canada, but little is known on the perinatal health status of First Nations people living on reserves. This study examines stillbirth and infant mortality rates among Aboriginal people in Quebec, notably, First Nations people living on reserves, and compares these rates with those of the province's non-Aboriginal population. DATA AND METHODS: Data on live births and stillbirths in Quebec from 1989 to 2008 were extracted from Statistics Canada's Infant Birth-Death Linked File. Postal codes were used to identify births and stillbirths on First Nations reserves, in the Cree and Naskapi communities (not on reserves), and in Inuit communities. Associations between type of community and mortality were measured using logistic regression models. RESULTS: Aboriginal people had a higher stillbirth rate than non-Aboriginal people in Quebec, but this difference was not significant after adjusting for socio-demographic characteristics (mothers' age and education, community size and isolation). Neonatal mortality was also higher among the Inuit. Post-neonatal mortality was higher among Aboriginal people, and was unrelated to differences in the mothers' age and education or to community size and isolation. Adjusted odds ratios (95% confidence intervals) for post-neonatal mortality on reserves, in the Cree and Naskapi communities, and in Inuit communities were, respectively, 1.57 (1.16 - 2.12), 3.01 (2.14 - 4.24) and 4.29 (3.09 - 5.97). INTERPRETATION: Stillbirth and infant mortality are higher among Aboriginal people than non-Aboriginal people in Quebec. The differences in post-neonatal mortality are particularly pronounced.

Temporal trends in social disparities in maternal smoking and breastfeeding in Canada, 1992-2008.

A steady decrease in maternal smoking during pregnancy and a steady increase in breastfeeding rates have been observed in Canada in the past two decades. However, the extent to which all socioeconomic classes have benefited from this progress is unknown. Therefore, this study was undertaken to determine: (1) whether progress achieved benefited the entire population or was limited to specific strata; and (2) whether disparities among strata decreased, stayed the same, or increased over time. We used data from the National Longitudinal Survey of Children and Youth, which enrolled children aged 0-3 years between 1994 and 2008. Data collected at entry was analyzed in a cross-sectional manner. Between birth years 1992-1996 and 2005-2008, smoking during pregnancy decreased from 11.5 % (95 % CI 10.0-13.0 %) to 5.2 % (95 % CI 4.1-6.3 %) among mothers with a college or university degree and from 43.0 % (95 % CI 38.8-47.2 %) to 38.6 % (95 % CI 32.9-44.2 %) among those with less than secondary education. During the same period, the rate of breastfeeding initiation increased from 83.8 % (95 % CI 81.9-85.6 %) to 91.5 % (95 % CI 90.2-92.8 %) among mothers with a college or university degree and from 63.1 % (95 % CI 58.9-67.4 %) to 74.7 % (95 % CI 69.8-79.7 %) among those with less than secondary education. The risks of smoking and of not breastfeeding remained significantly higher in the least educated category than in the most educated throughout the study period, and these associations remained statistically significant after controlling for maternal age. Gaps between the least and the most educated mothers narrowed for breastfeeding but widened for smoking during pregnancy.

Determinants of non-vaccination against seasonal influenza during pregnancy.

OBJECTIVE: The objective of this study was to identify the determinants of influenza non-vaccination during pregnancy in Canada. METHODS: Biological mothers of children born between December 2018 and March 2019 were surveyed about vaccinations they had received during pregnancy, reasons for non-vaccination, obstetrical history, and demographics. Simple and multiple logistic regression models were used to measure associations between various sociodemographic factors as well as obstetrical history, and non-vaccination against influenza. We analyzed data from 2361 mothers. RESULTS: Factors associated with non-vaccination included being followed during pregnancy by a midwife compared to by an obstetrician-gynecologist (OR 2.02; 95% CI, 1.17‒3.50); having two or more past live births compared to none (OR 1.58; 95% CI, 1.01‒2.49); having an education level below high school diploma compared to a bachelor's degree or above (OR 2.50; 95% CI, 1.06‒5.90); and having a household income below $60,000 (OR 2.46; 95% CI, 1.42‒4.24) or between $60,000 and $99,999 (OR 2.77; 95% CI, 1.70‒4.52) compared to a household income of $140,000 or more. The province or territory of prenatal care proved to be an important factor in non-vaccination, with statistically significant odds ratios for certain provinces: OR 7.50 (95% CI, 1.40‒40.26) for Ontario, 8.23 (95% CI, 1.53‒44.23) for Newfoundland and Labrador, and 11.39 (95% CI, 2.14‒60.60) for Quebec, as compared to the territories. CONCLUSION: Despite universal access to influenza vaccines in Canada during pregnancy, regional variations and socioeconomic disparities in non-vaccination are still observable.

RéSUMé: OBJECTIF: Identifier les déterminants de la non-vaccination contre la grippe pendant la grossesse au Canada. MéTHODES: Notre étude porte sur 2 361 mères biologiques d'enfants nés entre décembre 2018 et mars 2019 qui ont été interrogées sur les vaccins reçus pendant leur grossesse, les raisons de non-vaccination, leurs antécédents obstétricaux, et leurs caractéristiques démographiques. Des modèles de régression logistique simple et multiple ont été utilisés pour mesurer les associations entre divers facteurs sociodémographiques, les antécédents obstétricaux, et la non-vaccination contre l'influenza. RéSULTATS: Les facteurs associés à la non-vaccination comprennent le suivi de grossesse par une sage-femme par rapport à un obstétricien-gynécologue (RC 2,02; IC 95% : 1,17‒3,50); avoir eu deux naissances vivantes ou plus par rapport à aucune (RC 1,58; IC 95% : 1,01‒2,49); avoir une scolarité inférieure au diplôme d'études secondaires par rapport à un baccalauréat ou plus (RC 2,50; IC 95% : 1,06‒5,90); et avoir un revenu du ménage inférieur à 60 000 $ (RC 2,46; IC 95% : 1,42‒4,24) ou entre 60 000 $ et 99 999 $ (RC 2,77; IC 95% : 1,70‒4,52) par rapport à un revenu ménager de 140 000 $ ou plus. La province ou le territoire de soins prénataux s'est avéré un facteur important de la non-vaccination avec des rapports de cote statistiquement significatifs pour certaines provinces : RC 7,50 (IC 95% : 1,40‒40,26) pour l'Ontario, 8,23 (IC 95% : 1,53‒44,23) pour Terre-Neuve-et-Labrador, et 11,39 (IC 95% : 2,14‒60,60) pour le Québec, comparativement aux territoires. CONCLUSION: Malgré l'accès universel aux vaccins antigrippaux au Canada durant la grossesse, des variations régionales et des disparités socioéconomiques en non-vaccination persistent.

Mechanistic basis of the dynamic response of TWIK1 ionic selectivity to pH.

Highly selective for K+ at neutral pH, the TWIK1 channel becomes permeable to Na+ upon acidification. Using molecular dynamics simulations, we identify a network of residues involved in this unique property. Between the open and closed states previously observed by electron microscopy, molecular dynamics simulations show that the channel undergoes conformational changes between pH 7.5-6 involving residues His122, Glu235, Lys246 and Phe109. A complex network of interactions surrounding the selectivity filter at high pH transforms into a simple set of stronger interactions at low pH. In particular, His122 protonated by acidification moves away from Lys246 and engages in a salt bridge with Glu235. In addition, stacking interactions between Phe109 and His122, which stabilize the selectivity filter in its K+-selective state at high pH, disappear upon acidification. This leads to dissociation of the Phe109 aromatic side chain from this network, resulting in the Na+-permeable conformation of the channel.