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Background: The role of breastfeeding in modulating epigenetic factors has been suggested as a possible mechanism conferring its benefits on child development but it lacks evidence. Using extensive DNA methylation data from the ALSPAC child cohort, we characterized the genome-wide landscape of DNA methylation variations associated with the duration of exclusive breastfeeding and assessed whether these variations mediate the association between exclusive breastfeeding and BMI over different epochs of child growth., Results: Exclusive breastfeeding elicits more substantial DNA methylation variations during infancy than at other periods of child growth. At the genome-wide level, 13 CpG sites in girls (miR-21, SNAPC3, ATP6V0A1, DHX15/PPARGC1A, LINC00398/ALOX5AP, FAM238C, NATP/NAT2, CUX1, TRAPPC9, OSBPL1A, ZNF185, FAM84A, PDPK1) and 2 CpG sites in boys (IL16 and NREP), mediate the association between exclusive breastfeeding and longitudinal BMI. We found enrichment of CpG sites located within miRNAs and key pathways (AMPK signaling pathway, insulin signaling pathway, endocytosis). Overall DNA methylation variation corresponding to 3 to 5 months of exclusive breastfeeding was associated with slower BMI growth the first 6 years of life compared to no breastfeeding and in a dose-response manner with exclusive breastfeeding duration., Conclusions: Our study confirmed the early postnatal period as a critical developmental period associated with substantial DNA methylation variations, which in turn could mitigate the development of overweight and obesity from infancy to early childhood. Since an accelerated growth during these developmental periods has been linked to the development of sustained obesity later in life, exclusive breastfeeding could have a major role in preventing the risks of overweight/obesity and children and adults through DNA methylation mechanisms occurring early in life., (© 2021. The Author(s).)

Paget's disease of bone (PDB) is characterized by excessive and disorganized bone remodeling, in which bone-resorbing osteoclasts play a key role. We investigated microRNA (miR) expression in osteoclasts derived from the blood of 40 PDB patients and 30 healthy controls. By deep sequencing, a preliminary analysis identified differentially expressed miRs in a discovery cohort of 9 PDB patients and 9 age and sex-matched healthy controls. Six mature miRs, miR-29b1-3p, miR-15b-5p, miR-181a-5p, let-7i-3p, miR-500b-5p, and miR-1246, were found to be significantly decreased in pagetic overactive osteoclasts. The differential expression of the miRs was confirmed by the analysis of a larger independent cohort using qPCR. In an integrative network biology analysis of the miR candidates, we identified strong validated interactions between the miRs and some pathways, primarily apoptosis, and major osteoclast signaling pathways including PI3K/Akt, IFNγ, or TGFβ, as well as c-Fos, a transcription factor, and MMP-9, a metalloprotease. In addition, other genes like CCND2, CCND1, WEE1, SAMHD1, and AXIN2 were revealed in this network of interactions. Our results enhance the understanding of osteoclast biology in PDB; our work may also provide fresh perspectives on the research or therapeutic development of other bone diseases. KEY MESSAGES: miR profile in overactive osteoclasts from patients with Paget's disease of bone. Six mature miRs were significantly decreased in pagetic osteoclasts vs controls. miRs of interest: let7i-3p, miR-15b-5p, -29b1-3p, -181a-5p, -500b-5p, and -1246. Target genes and enriched pathways highlight the importance of apoptotic pathways., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The study aimed at documenting motivational orientations for the regulation of eating as defined by self-determination theory and their association with sociodemographic characteristics and overall diet quality. As part of the PREDISE study, French-speaking women (n = 550) and men (n = 547), aged 18-65 years, living in the Province of Québec, Canada, completed online validated questionnaires. The Regulation of Eating Behavior Scale, based on the self-determination theory, assessed self-determined and non-self-determined motivation to regulate one's eating behavior. Three web-based 24-h food recalls were completed and used to compute the Canadian Healthy Eating Index 2007 (C-HEI), an indicator of the overall adherence to Canadian guidelines for healthy eating. Multiple linear regressions were performed to assess how regulation styles are associated with the C-HEI. Model 1 included no covariate, model 2 included sociodemographic covariates, and fully adjusted model 3 included as covariates sociodemographic variables as well as variables that were previously associated with diet quality, namely nutrition knowledge and social support for healthy eating. Women (p < 0.0001), older individuals (p = 0.0002), those with a higher education level (p < 0.0001), and non-smokers (p < 0.0001) reported higher self-determined motivation score than their counterparts. Self-determined motivation was positively (model 1: B = 4.67, p < 0.0001; model 2: B = 3.82, p < 0.0001; model 3: B = 3.61, p < 0.0001) and non-self-determined motivation was negatively (model 1: B = -1.62, p = 0.0009; model 2: B = -1.63, p = 0.0006; model 2: B = -1.49, p = 0.0022) associated with C-HEI. The present study suggests that some subgroups of the general adult population show more self-determined motivation for eating, which is associated with a better diet quality independently of individual characteristics and other individual and social determinants of healthy eating. Strategies to help individuals internalize the regulation of eating should be further investigated., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Maternal insulin resistance is associated with greater maternal inflammation during pregnancy, but its relation to inflammation in offspring remains unclear. The goal of this study was to assess the relationship of gestational insulin resistance and other glycemic markers with offspring inflammation at birth and at 5 years of age., Methods: We included 653 mother-child pairs from the prospective pre-birth Gen3G cohort. We examined maternal insulin and glucose levels measured during the second trimester of pregnancy, from which we derived the homeostatic model of assessment of insulin resistance (HOMA-IR) and the Matsuda index. We assessed offspring inflammation at birth and at 5 years of age by measuring plasma tumor necrosis factor-α (TNFα) concentrations. We conducted multivariable regression models to evaluate associations of each insulin and glucose marker with offspring inflammation adjusting for confounding variables., Results: Higher levels of fasting insulin were associated with lower TNFα levels at birth (-0.78, 95% CI [-1.45, -0.11]), in the fully adjusted model. We observed similar associations with the HOMA-IR and opposite direction with the Matsuda index. We did not find persistence of the association between maternal fasting insulin and offspring TNFα at 5 years of age., Conclusions: Greater maternal insulin resistance during pregnancy was associated with lower cord blood TNFα levels in newborns. The mechanisms by which maternal insulin resistance may promote lower inflammatory levels in newborns are not fully understood and more research is needed to deepen our understanding of these mechanisms., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The Saguenay-Lac-Saint-Jean (SLSJ) region located in the province of Quebec was settled in the 19th century by pioneers issued from successive migration waves starting in France in the 17th century and continuing within Quebec until the beginning of the 20th century. The genetic structure of the SLSJ population is considered to be the product of a triple founder effect and is characterised by a higher prevalence of some rare genetic diseases. Several studies were performed to elucidate the historical, demographic and genetic background of current SLSJ inhabitants to assess the origins of these rare disorders and their distribution in the population. Thanks to the development of new sequencing technologies, the genes and the variants responsible for the most prevalent conditions were identified. Combined with other resources such as the BALSAC population database, identifying the causal genes and the pathogenic variants allowed to assess the impacts of some of these founder mutations on the population health and to design precision medicine public health strategies based on carrier testing. Furthermore, it stimulated the establishment of many public programmes.We report here a review and an update of a subset of inherited disorders and founder mutations in the SLSJ region. Data were collected from published scientific sources. This work expands the knowledge about the current frequencies of these rare disorders, the frequencies of other rare genetic diseases in this population, the relevance of the carrier tests offered to the population, as well as the current available treatments and research about future therapeutic avenues for these inherited disorders., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This study compared quality indicators across linguistic groups and sought to determine whether disparities are influenced by resident-facility language discordance in long-term care., Design: Population-based retrospective cohort study using linked databases., Setting and Participants: Retrospective cohort of newly admitted residents of long-term care facilities in Ontario, Canada, between 2010 and 2016 (N=47,727). Individual residents' information was obtained from the Resident Assessment Instrument Minimum Data Set (RAI-MDS) to determine resident's primary language, clinical characteristics, and health care indicators., Measures: Main covariates of interest were primary language of the resident and predominant language of the long-term care facility, which was determined using the French designation status as defined in the French Language Services Act. Primary outcomes were a set of quality and safety indicators related to long-term care: worsening of depression, falls, moderate-severe pain, use of antipsychotic medication, and physical restraints. Multivariable logistic regression models were used to assess the impact of resident's primary language, facility language, and resident-facility language discordance on each quality indicator., Results: Overall, there were few differences between francophones and anglophones for quality and safety indicators. Francophones were more likely to report pain (10.9% vs 9.9%; P = .001) and be physically restrained (7.3% vs 5.2%; P < .001), whereas a greater proportion of anglophones experienced worsening of depressive symptoms (24.0% vs 22.9%; P = .001). However, quality indicators were generally worse for francophones in Non-Designated facilities, except for pain, which was more commonly reported by francophones in French-Designated facilities. Anglophones were more likely to be physically restrained in French-Designated facilities (6.7% vs 5.1%; P < .001)., Conclusions and Implications: For francophones, quality indicators tended to be worse in the presence of resident-facility language discordance. However, these findings did not persist after adjusting for individual- and facility-level characteristics, suggesting that the disparities observed at the population level cannot be attributed to linguistic factors alone., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Exposure to maternal hyperglycaemia in pregnancy has been associated with childhood obesity. Leptin regulation might be involved in this 'adiposity programming' and may depend on timing of exposure., Objectives: To investigate associations of maternal glycaemia at different periods in pregnancy with childhood adiposity and leptin levels at 5 years of age., Methods: In a prospective pre-birth cohort, we measured maternal glucose levels after a 50 g oral glucose challenge test at first trimester (9.8 ± 2.3 weeks) and during a 75 g oral glucose tolerance test at second trimester (26.5 ± 0.9 weeks). We followed up children at 5 years; we measured anthropometry and body composition using dual-energy X-ray absorptiometry (DXA). We measured fasting leptin levels using immunoassays (Luminex) in 328 children. We conducted linear regression analyses, adjusting for potential confounders., Results: Maternal glycaemia at first trimester was associated with childhood leptin levels at 5 years, independently of maternal pre-pregnancy BMI and other confounders (β = .09 ± .04; P = .03). Higher post-load glucose levels at second trimester were associated with greater total body fat percentage measured by DXA (1 hour-glucose: β = .010 ± .004; P = .03 and 2 hours-glucose: β = .016 ± .005; P = .002), but not with leptin levels., Conclusions: Our results suggest that programming of leptin regulation may be sensitive to maternal hyperglycaemia specifically in early pregnancy., (© 2021 World Obesity Federation.)

It has been suggested that older adults from minority linguistic and ethnic communities face higher risks of being socially excluded. The aim of this review was, therefore, to explore and review social exclusion studies conducted among official language minority older adults in three countries, namely Canada, Finland and Wales. A rapid review approach was used to review scientific literature in line with six social exclusion domains. The literature searches were made in Finnish, Swedish, English, French and Welsh and were restricted to research published within the timeline of 2001 - September 2019 and yielded 42 articles. The included studies were categorized into three different domains: socioeconomic influences, social participation and societal conditions. Converging and diverging patterns of social exclusion in old age were identified between the linguistic minorities. Linguistic barriers regarding access to health care and receiving health information were common across the three linguistic contexts, whereas exclusion from social participation was noticed amongst the linguistic minorities in Canada and Wales. Some connections between belonging to a linguistic minority and being exposed to a lower socioeconomic status and higher poverty risk were made, however, these findings were not robust across all three countries. The findings indicated that experiences of exclusion could be considered fairly common among linguistic minority older adults. We conclude that the research evidence presented in the review sheds light on issues of social inequality in old age between linguistic majorities and minorities, thus identifying important aspects of social exclusion to guide future research as well as policy and practice., (© 2021. The Author(s).)

Background: Previous studies suggest that fetal programming to hyperglycemia in pregnancy is due to modulation of DNA methylation (DNAm), but they have been limited in their maternal glycemic characterization. Methods: In the Gen3G study, we used a principal component analysis to integrate multiple glucose and insulin values measured during the second trimester oral glucose tolerance test. We investigated associations between principal components and cord blood DNAm levels in an epigenome-wide analysis among 430 mother-child pairs. Results: The first principal component was robustly associated with lower DNAm at cg26974062 ( TXNIP ; p = 9.9 × 10 -9 ) in cord blood. TXNIP is a well-known DNAm marker for type 2 diabetes in adults. Conclusion: We hypothesize that abnormal glucose metabolism in pregnancy may program dysregulation of TXNIP across the life course.

Maternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. Here we present a meta-analysis of the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (N = 1700, 344 with MSDP). We identify 443 CpGs that are associated with MSDP, of which 142 associated with birth outcomes, 40 associated with gene expression, and 13 CpGs are associated with all three. Only two CpGs have consistent associations from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP-associated CpGs are enriched for environmental response genes, growth-factor signaling, and inflammation, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth., (© 2021. The Author(s).)

Aim: To investigate the associations between high-density lipoprotein (HDL)-enriched miRNAs and the cardiometabolic profile of healthy men and women. Patients & methods: miRNAs were quantified using next-generation sequencing of miRNAs extracted from purified HDL and plasma from 17 healthy men and women couples. Results: Among the HDL-enriched miRNAs, miR-30a-5p correlated positively with HDL-cholesterol levels, whereas miR-144-5p and miR-30a-5p were negatively associated with fasting insulin levels and Homeostasis model assessment of insulin resistance index. Overall, miR-30a-5p, miR-150-5p and sex contributed to 45% of HDL-cholesterol variance. A model containing only miR-30a-5p, age and sex explained 41% of fasting glucose variance. Conclusion: HDL-enriched miRNAs, notably miR-30a-5p, are associated with cardiometabolic markers. These miRNAs could play a role in HDL's protective functions, particularly regarding glucose-insulin homeostasis.

Background: Epigenome-wide association studies (EWAS) have provided opportunities to understand the role of epigenetic mechanisms in development and pathophysiology of many chronic diseases. However, an important limitation of conventional EWAS is that profiles of epigenetic variability are often obtained in samples of mixed cell types. Here, we aim to assess whether changes in cord blood DNA methylation (DNAm) associated with gestational diabetes mellitus (GDM) exposure and early childhood growth markers occur in a cell type-specific manner., Results: We analyzed 275 cord blood samples collected at delivery from a prospective pre-birth cohort with genome-wide DNAm profiled by the Illumina MethylationEPIC array. We estimated proportions of seven common cell types in each sample using a cord blood-specific DNAm reference panel. Leveraging a recently developed approach named CellDMC, we performed cell type-specific EWAS to identify CpG loci significantly associated with GDM, or 3-year-old body mass index (BMI) z-score. A total of 1410 CpG loci displayed significant cell type-specific differences in methylation level between 23 GDM cases and 252 controls with a false discovery rate < 0.05. Gene Ontology enrichment analysis indicated that LDL transportation emerged from CpG specifically identified from B-cells DNAm analyses and the mitogen-activated protein kinase pathway emerged from CpG specifically identified from natural killer cells DNAm analyses. In addition, we identified four and six loci associated with 3-year-old BMI z-score that were specific to CD8+ T-cells and monocytes, respectively. By performing genome-wide permutation tests, we validated that most of our detected signals had low false positive rates., Conclusion: Compared to conventional EWAS adjusting for the effects of cell type heterogeneity, the proposed approach based on cell type-specific EWAS could provide additional biologically meaningful associations between CpG methylation, prenatal maternal GDM or 3-year-old BMI. With careful validation, these findings may provide new insights into the pathogenesis, programming, and consequences of related childhood metabolic dysregulation. Therefore, we propose that cell type-specific analyses are worth cautious explorations.

Purpose: To quantify eye lens dose in interventional radiology and assess whether neck dosimeter is a good surrogate to evaluate eye lens dosimetry., Methods: Radiation exposure was prospectively measured in 9 interventional radiologists between May and October 2017. Standard Hp(0,07) thermoluminescent dosimeters (TLDs) were worn at the neck outside the lead apron, and 2 dedicated eye lens Hp(3) TLDs were placed just above the eyes, one midline and another at the outer edge of the left eye. Correlations between eye lens and neck TLD doses were assessed with Pearson coefficient, and linear regression was used to predict eye lens dose from neck TLD values., Results: Eye lens dose without eye protection was 0.18 ± 0.11 (mean ± standard deviation; 0.08-0.41) mSv per workday and 35.3 ± 6.6 mSv (16.3-82.9) annually (200 workdays/year). Five (56%) radiologists exceeded the 20 mSv annual eye lens dose limit. Eye lens doses from left and central TLDs were 12.46 ± 3.02 and 9.29 ± 3.38 mSv, respectively ( P = .027). Mean eye lens (left and central) and neck TLD doses were 10.87 ± 2.67 and 16.56 ± 5.67 mSv, respectively ( P = .008). Pearson correlation coefficient between both eye lens TLD and between mean eye lens TLD and neck TLD doses were 0.91 and 0.92, respectively. Average of eye lens dose was 0.0179 + (0.5971 × neck dose)., Conclusion: Full-time interventional radiologists are likely to suffer from deterministic radiation effects to the eye lens, especially on the left side. Neck TLD significantly overestimates eye lens dose. However, eye lens doses are highly correlated with neck doses and may be predicted from the neck TLD values.

Background: Doctor of Nursing Practice (DNP) students often experience challenges that can cause poor academic performance and attrition. Known threats to nurses' professional quality of life and patient care include compassion fatigue and presenteeism; it is not known how these phenomena carry over from prior nursing experience to DNP students' academic experiences and subsequent NP practice. Adverse Childhood Experiences (ACEs) can also threaten nursing students' coping ability and overall wellbeing. Building resilience can combat the negative effects related to professional quality of life and traumatic experiences and promote nursing student success., Objectives: Measure compassion fatigue, presenteeism, ACEs, and resiliency in DNP students., Design: A cross-sectional survey was conducted with three cohorts of DNP students., Setting: A DNP program at a large public American University., Participants: DNP students (n = 118) from four NP specialty tracks: Family, Pediatric, Psychiatric Mental Health, and Adult-Gerontology Acute Care., Methods: Online surveys were sent to three cohorts of DNP students: one group before beginning the program and two groups, one year apart, before starting clinical rotations in the program. Surveys included measures for compassion fatigue, presenteeism, ACEs, and resiliency., Results: The demographics of this study sample was similar to other published DNP student samples. The students reported moderate levels of compassion fatigue, presenteeism, and resiliency. ACE scores ranged from 0 to 8 out of 10, and 50% reported at least one ACE., Conclusions: Survey results from three DNP student cohorts indicate that many are pursuing advanced practice nursing education with a history of traumatic childhood events, demands of balancing work and school, and moderate resiliency levels. Many have symptoms of negative professional quality of life and presenteeism that could inhibit their job satisfaction and quality of care as an NP. Promoting DNP students' resiliency may improve their ability to thrive amidst academic and professional challenges., (Copyright © 2021. Published by Elsevier Ltd.)

Introduction: Childhood overweight and obesity (OWO) is a primary global health challenge. Childhood OWO prevention is now a public health priority in China. The Sino-Canadian Healthy Life Trajectories Initiative (SCHeLTI), one of four trials being undertaken by the international HeLTI consortium, aims to evaluate the effectiveness of a multifaceted, community-family-mother-child intervention on childhood OWO and non-communicable diseases risk., Methods and Analysis: This is a multicentre, cluster-randomised, controlled trial conducted in Shanghai, China. The unit of randomisation is the service area of Maternal Child Health Units (N=36). We will recruit 4500 women/partners/families in maternity and district level hospitals. Participants in the intervention group will receive a multifaceted, integrated package of health promotion interventions beginning in preconception or in the first trimester of pregnancy, continuing into infancy and early childhood. The intervention, which is centred on a modified motivational interviewing approach, will target early-life maternal and child risk factors for adiposity. Through the development of a biological specimen bank, we will study potential mechanisms underlying the effects of the intervention. The primary outcome for the trial is childhood OWO (body mass index for age ≥85th percentile) at 5 years of age, based on WHO sex-specific standards. The study has a power of 0.8 (α=0.05) to detect a 30% risk reduction in the proportion of children with OWO at 5 years of age, from 24.4% in the control group to 17% in the intervention group. Recruitment was launched on 30 August 2018 for the pilot study and 10 January 2019 for the formal study., Ethics and Dissemination: The study has been approved by the Medical Research Ethics Committee of the International Peace Maternity and Child Health Hospital in Shanghai, China, and the Research Ethics Board of the Centre Intégré Universitaire de Santé et Services Sociaux de l'Estrie-CHUS in Sherbrooke, Canada. Data sharing policies are consistent with the governance policy of the HeLTI consortium and government legislation., Trial Registration Number: ChiCTR1800017773., Protocol Version: November 11, 2020 (Version #5)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Fetal exposure to maternal excess adiposity and hyperglycemia is risk factors for childhood adverse metabolic outcomes. Using data from a prospective pre-birth cohort, we aimed to further understand the prenatal determinants of fetal metabolic programming based on analyses of maternal adiposity and glycemic traits across pregnancy with childhood metabolomic profiles., Methods: This study included 330 mother-child pairs from the Gen3G cohort with information on maternal adiposity and glycemic markers at 5-16 (visit 1) and 24-30 (visit 2) weeks of pregnancy. At mid-childhood (4.8-7.2 years old), we collected fasting plasma and measured 1116 metabolites using an untargeted approach. We constructed networks of interconnected metabolites using a weighted-correlation network analysis algorithm. We estimated Spearman's partial correlation coefficients of maternal adiposity and glycemic traits across pregnancy with metabolite networks and individual metabolites, adjusting for maternal age, gravidity, race/ethnicity, history of smoking, and child's sex and age at blood collection for metabolite measurement., Results: We identified a network of 16 metabolites, primarily glycero-3-phosphoethanolamines (GPE) at mid-childhood that showed consistent negative correlations with maternal body mass index, waist circumference, and body-fat percentage at visits 1 and 2 (ρ adjusted  = -0.14 to -0.21) and post-challenge glucose levels at visit 2 (ρ adjusted  = -0.10 to -0.13), while positive correlations with Matsuda index (ρ adjusted  = 0.13). Within this identified network, 1-palmitoyl-2-decosahexaenoyl-GPE and 1-stearoyl-2-decosahexaenoyl-GPE appeared to be driving the associations. In addition, a network of 89 metabolites, primarily phosphatidylcholines, plasmalogens, sphingomyelins, and ceramides showed consistent negative correlations with insulin at visit 1 and post-challenge glucose at visit 2, while positive correlation with adiponectin at visit 2., Conclusions: Prenatal exposure to maternal higher adiposity and hyperglycemic traits and lower insulin sensitivity markers were associated with a unique metabolomic pattern characterized by low serum phospho- and sphingolipids in mid-childhood.

Purpose: To assess whether angioplasty of hemodialysis access (HA) stenosis with a drug-coated balloon (DCB) would prevent restenosis in comparison with plain-balloon percutaneous transluminal angioplasty (PTA)., Materials and Methods: This prospective randomized clinical trial enrolled 120 patients with dysfunctional arteriovenous fistulae (n = 109) and grafts (n = 11), due to a ≥50% stenosis between March 2014 and April 2018. All patients underwent high-pressure balloon angioplasty and were then randomized to either DCB (n = 60) or PTA (n = 60). Patients were followed-up for 1 year, and angiography was performed 6 months after angioplasty. The primary endpoint was the late lumen loss (LLL) at 6 months. Secondary endpoints included other angiographic parameters at 6 months and HA failures, adverse event, and mortality at 12 months. Continuous variables were compared with a Student t-test, and Kaplan-Meier curves were used for freedom from HA failure and for mortality., Results: LLL in the DCB and in the PTA group were 0.64 mm ± 1.20 and 1.13 mm ± 1.51, respectively (P = .082, adjusted P = .0498). DCB was associated with lower percentage stenosis (54.2% ± 19.3 vs 61.7% ± 18.2; P = .047) and binary restenosis ≥50% (56.5% vs 81.1%; P = .009) than PTA. The number of HA failures after 12 months was lower for DCB than for PTA (45% vs 66.7%; P = .017). Mortality at 12 months was 10% and 8.3% in the DCB and PTA groups, respectively (P = .75)., Conclusions: Despite LLL improvement that failed to reach statistical significance, this study demonstrated decreased incidence and severity of restenosis with DCB compared with PTA to treat dysfunctional HA., (Copyright © 2020 SIR. Published by Elsevier Inc. All rights reserved.)

Aim: The placenta undergoes DNA methylation (DNAm) programming that is unique compared with all other fetal tissues. We aim to decipher some of the physiologic roles of the placenta by comparing its DNAm profile with that of another fetal tissue. Materials & methods: We performed a comparative analysis of genome-wide DNAm of 444 placentas paired with cord blood samples collected at birth. Gene ontology term analyses were conducted on the resulting differentially methylated regions. Results: Genomic regions upstream of transcription start sites showing lower DNAm in the placenta were enriched with terms related to miRNA functions and genes encoding G-protein-coupled receptors. Conclusion: These results highlight genomic regions that are differentially methylated in the placenta in contrast to fetal blood.

Aim: We evaluated five methods for detecting differentially methylated regions (DMRs): DMRcate, comb-p, seqlm, GlobalP and dmrff. Materials & methods: We used a simulation study and real data analysis to evaluate performance. Additionally, we evaluated the use of an ancestry-matched reference cohort to estimate correlations between CpG sites in cord blood. Results: Several methods had inflated Type I error, which increased at more stringent significant levels. In power simulations with 1-2 causal CpG sites with the same direction of effect, dmrff was consistently among the most powerful methods. Conclusion: This study illustrates the need for more thorough simulation studies when evaluating novel methods. More work must be done to develop methods with well-controlled Type I error that do not require individual-level data.

Background: Gestational hyperglycemia is associated with adverse perinatal outcomes and long-term offspring metabolic programming, likely through dysregulation of DNA methylation (DNAm). Materials & methods: We tested associations between maternal HbA1c and cord blood DNAm among 412 mother-child pairs in the genetics of glucose regulation in gestation and growth (Gen3G) and implemented Mendelian randomization to infer causality. We sought replication in an independent sample from Healthy Start. Results: Higher second trimester HbA1c levels were associated with lower DNAm at cg21645848 (p = 3.9 × 10 -11 ) near URGCP . Mendelian randomization and replication analyses showed same direction of effect between HbA1c and DNAm at cg21645848, but did not reach statistical significance. Conclusion: We found that higher maternal glycemia reflected by HbA1c is associated with cord blood DNAm at URGCP , a gene related with inflammatory pathways.

Purpose: To assess how nutrition knowledge is associated with global diet quality and to investigate whether sociodemographic characteristics (ie, sex, age, education, income, marital status, and living with children or not) moderate this association., Design: Cross-sectional web-based study., Participants: The PREDISE study aims at identifying correlates of adherence to healthy eating guidelines in French-speaking adults from the Province of Quebec, Canada., Subjects: A probability sample of 1092 participants (50% female)., Measures: The Nutrition Knowledge Questionnaire and 24-hour food recalls from which the Canadian Healthy Eating Index (C-HEI) was calculated., Analysis: Multiple linear regressions performed to assess how nutrition knowledge is associated with the C-HEI. Interaction terms tested to evaluate whether sociodemographic characteristics moderate the association between nutrition knowledge and the C-HEI., Results: Nutrition knowledge (B = 0.141 [95% CI: 0.075-0.208], P < .0001) was identified as a significant correlate of the C-HEI. Education significantly moderated the association between nutrition knowledge and the C-HEI ( P interaction = .0038), with a significative association among participants with a lower education level (B = 0.295 [95% CI: 0.170-0.421], P < .0001) but not among participants with a higher education level (B = 0.077 [95% CI: -0.004 to 0.157], P = .06). Whether participants lived with or without children also significantly moderated the association ( P interaction = 0.0043); nutrition knowledge was associated with the C-HEI only in participants who were not living with children (B = 0.261 [95% CI: 0.167 to 0.355], P < .0001)., Conclusion: This study suggests that the association between nutrition knowledge and adherence to healthy eating guidelines is not the same in different subgroups of the population. Interventions aiming at increasing nutrition knowledge may be a promising approach to improve diet quality, especially among individuals with a lower education.

Hundreds of common genetic variants acting through distinguishable physiologic pathways influence the risk of type 2 diabetes (T2D). It is unknown to what extent the physiology underlying gestational diabetes mellitus (GDM) is distinct from that underlying T2D. In this study of >5,000 pregnant women from three cohorts, we aimed to identify physiologically related groups of maternal variants associated with GDM using two complementary approaches that were based on Bayesian nonnegative matrix factorization (bNMF) clustering. First, we tested five bNMF clusters of maternal T2D-associated variants grouped on the basis of physiology outside of pregnancy for association with GDM. We found that cluster polygenic scores representing genetic determinants of reduced β-cell function and abnormal hepatic lipid metabolism were associated with GDM; these clusters were not associated with infant birth weight. Second, we derived bNMF clusters of maternal variants on the basis of pregnancy physiology and tested these clusters for association with GDM. We identified a cluster that was strongly associated with GDM as well as associated with higher infant birth weight. The effect size for this cluster's association with GDM appeared greater than that for T2D. Our findings imply that the genetic and physiologic pathways that lead to GDM differ, at least in part, from those that lead to T2D., (© 2020 by the American Diabetes Association.)

Objectives : Although the rate of cannabis use by older adults is increasing more quickly than all other age groups, little is known about the reasons older adults use cannabis and the outcomes they experience. With this research, we investigated older adults' perceptions and experiences of medical cannabis use to treat and/or manage chronic conditions, specifically as a substitute for prescription drugs. Methods : Researchers relied on qualitative inquiry in the form of semi-structured, one-on-one interviewing to investigate the phenomenon of medical cannabis use for the management of chronic conditions. Results : Our findings suggest that older adults are open to medical cannabis as an alternative to pharmaceutical drugs, hopeful with regard to the management of symptoms and pain, and aware of and astute at managing issues related to stigma both from their physicians and family and friends. Furthermore, older adults describe the frustrations with education, awareness, and lack of support with dosing. Conclusions : Participations found medical cannabis use to be beneficial in managing chronic conditions and alleviating symptoms such as chronic pain. Findings are presented as an interpretation of the participants' perceptions of their medical cannabis use. Implications for putting medical cannabis use into everyday practice as well as policy implications are considered. Clinical Implications : This information will help clinicians better support older adults desiring to use medical cannabis. This research will help clinicians learn more about factors impacting medical cannabis use, and the types of information and assistance that may aid older adults in their health and well-being with the use of medical cannabis to treat chronic conditions.

Aim: Myotonic dystrophy type 1 (DM1) is caused by an unstable trinucleotide (CTG) expansion at the DMPK gene locus. Cognitive dysfunctions are often observed in the condition. We investigated the association between DMPK blood DNA methylation (DNAm) and cognitive functions in DM1, considering expansion length and variant repeats (VRs). Method: Data were obtained from 115 adult-onset DM1 patients. Molecular analyses consisted of pyrosequencing, small pool PCR and Southern blot hybridization. Cognitive functions were assessed by validated neuropsychological tests. Results: For patients without VRs (n = 103), blood DNAm at baseline independently contributed to predict cognitive functions 9 years later. Patients with VRs (n = 12) had different DNAm and cognitive profiles. Conclusion: DNAm allows to better understand DM1-related cognitive dysfunction etiology.

Purpose: The effectiveness of the standard biliopancreatic diversion with duodenal switch (BPD/DS) in terms of weight loss has been demonstrated. Increasing the strict alimentary limb length while maintaining the length of the common channel could lead to similar weight loss while reducing side effects., Materials and Methods: The objective was to evaluate the effect of increasing the strict alimentary limb length on weight loss, comorbidities, nutritional deficiencies, and quality of life 2 years after surgery, compared with standard BPD/DS. An exploratory randomized, double-blind study evaluated the results of LADS at 2 years in comparison with the standard BPD/DS. Common channel was kept at 100 cm in both groups while alimentary limb was created at 100 cm from Treitz angle in the LADS group and at 150 cm total in the BPD/DS group., Results: Twenty patients were recruited from May 2013 to June 2015. Mean percentage of excess weight loss was statistically significantly lower in the LADS group at 24 months (81.6 ± 6.6% in the LADS group and 97.1 ± 11.1% in the BPD/DS group (p = 0.001). No significant difference regarding the rate of remission of comorbidities was noted. Mean calcium, vitamin D, hemoglobin, zinc, and copper levels were statistically lower in the BPD/DS group. Quality of life was significantly improved in both groups, with no statistically significant difference between the two groups., Conclusions: At 24 months, weight loss was lower in the LADS group. However, no difference was observed in the improvement in quality of life. LADS technique was discontinued following this study., Trial Registration: ClinicalTrial.gov Ref. NCT03097926.

Vascular pseudoaneurysms are a rare yet life-threatening complication of untreated pancreatic pseudocysts related to their high risk of rupture and bleeding. Several studies and reports have established endovascular approaches as a successful first-line therapy in the management of arterial pancreatic pseudoaneurysms. However, no reports have been published describing endovascular repair of a venous pseudoaneurysm that developed after infection of a chronically stable pancreatic pseudocyst, most likely due to its rare occurrence. We report in this technical note the treatment of a superior mesenteric vein pseudoaneurysm that developed as a result of an infected small pancreatic pseudocyst, by radiologic placement of a covered endovascular stent.

MicroRNA (miRs) are small, non-coding RNA that post-transcriptionally regulate DNA expression. We hypothesized that specific miR profiles may be a feature of overactive osteoclasts in Paget's disease of bone (PDB), a disorder characterized by an increased and disorganized bone remodeling that typically begins with excessive bone resorption. We compared the expression profile of 13 miRs in human osteoclasts differentiated in vitro from peripheral blood mononuclear cells (PBMCs) of patients with PDB (n = 10) or age- and sex- matched healthy subjects (n = 10). We selected 13 miRs for testing, on the basis of their previously reported roles either in human osteoclast differentiation, in bone diseases, or in osteoclast important signaling pathways. From those expression results, 3 miRNAs were further selected for in-vitro studies aiming at modulating miR expression in human cord blood monocyte derived osteoclasts: 2 miRs (miR-146a-3p and miR-155-5p) whose expression was significantly reduced in pagetic osteoclasts, as well as miRNA-133a-3p, stable in PDB relative to controls, but with known regulatory importance within osteoclasts. We demonstrated a positive (miR-133a-3p) or negative (miR-155-5p, miR-146a-3p) impact of those miRs on the formation of osteoclasts and/or their bone resorption capacity in this human model. Signaling pathways were significantly affected, including p38 MAP-kinase (miR-133a-3p), RANKL-induced TRAF6/NFκB signaling (miR-146a-3p), and MITF expression (miR-155-5p). Osteoclast miRNA profiles might have an important value to yield significant new insights into the osteoclast phenotype in PDB and in other bone diseases with hyperactive osteoclasts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The purpose of this study was to explore the lived experiences of politically engaged hospital staff nurses, the way in which they would like to practice, as well as the ideas and actions they have undertaken to foster change in their nursing practice. A qualitative design was used to collect data from a purposive sample of 39 nurses. Results indicate a deprofessionalization of nursing and a drift toward authoritarianism. There are, nonetheless, nurses who employ acts of resistance with the aim of establishing new power relations. It appears that those actions must focus on the radical renewal of democracy in hospitals.

The aim of this study was to identify placental DNA methylation (DNAm) variations associated with adiposity at 3 years of age. We quantified placental DNAm using the Infinium MethylationEPIC BeadChips. We assessed associations between DNAm at single-CpGs and skinfold thickness using robust linear regression models adjusted for gestational age, child's sex, age at follow-up and cellular heterogeneity. We sought replication of DNAm association with child adiposity in an independent cohort. We quantified placental mRNA levels for annotated gene using qRT-PCR and tested for correlation with DNAm. Lower DNAm at cg22593959 and cg22436429 was associated with higher adiposity ( β = -1.18, q = 0.002 and β = -0.82, q = 0.04). The cg22593959 is located in an intergenic region (chr7q31.3), whereas cg22436429 is within the TFAP2E gene (1p34.3). DNAm at cg22593959 and cg22436429 was correlated with mRNA levels at FAM3C (r s = -0.279, p = 0.005) and TFAP2E (r s = 0.216, p = 0.03). In an independent cohort, the association between placental DNAm at cg22593959 and childhood adiposity was of similar strength and direction ( β = -3.8 ± 4.1, p = 0.36), yet non-significant. Four genomic regions were also associated with skinfold thickness within FMN1 , MAGI2 , SKAP2 and BMPR1B genes. We identified placental epigenetic variations associated with adiposity at 3 years of age suggesting that childhood fat accretion patterns might be established during fetal life.

Placental lipids transfer is essential for optimal fetal development, and alterations of these mechanisms could lead to a higher risk of adverse birth outcomes. Low-density lipoprotein receptor (LDLR), LDL receptor-related protein 1 (LRP1), and scavenger receptor class B type 1 (SCARB1) genes are encoding lipoprotein receptors expressed in the placenta where they participate in cholesterol exchange from maternal to fetal circulation. The aim of this study was thus to investigate the association between maternal lipid changes occurring in pregnancy, placental DNA methylation (DNAm) variations at LDLR, LRP1, and SCARB1 gene loci, and newborn's anthropometric profile at birth. Sixty-nine normoglycemic women were followed from the first trimester of pregnancy until delivery. Placental DNAm was quantified at 43 Cytosine-phosphate-Guanines (CpGs) at LDLR, LRP1, and SCARB1 gene loci using pyrosequencing: 4 CpGs were retained for further analysis. Maternal clinical data were collected at each trimester of pregnancy. Newborns' data were collected from medical records. Statistical models included minimally newborn sex and gestational and maternal age. Maternal total cholesterol changes during pregnancy (ΔT3-T1) were correlated with DNAm variations at LDLR (r = -0.32, p = 0.01) and LRP1 (r = 0.34, p = 0.007). DNAm at these loci was also correlated with newborns' cord blood triglyceride and leptin levels. Mediation analysis supports a causal relationship between maternal cholesterol changes, DNAm levels at LRP1 locus, and cord blood leptin concentration (pmediation = 0.02). These results suggest that LRP1 DNAm link maternal blood cholesterol changes in pregnancy and offspring adiposity at birth, which provide support for a better follow-up of blood lipids in pregnancy.

Background: Introducing complementary foods other than breastmilk or formula acutely changes the infant gut microbiota composition. However, it is unknown whether the timing of introduction to complementary foods (early vs. late) in infancy is associated with early childhood gut microbiota and BMI, and if these associations depend on breastfeeding duration., Objective: Our primary objective was to investigate whether timing of infant complentary feeding with solid foods is associated with early childhood gut microbiota composition and BMI-z, and whether these associations differ by duration of breastfeeding., Methods: We used data from a Canadian pre-birth cohort followed till age 5 years. We examined timing of introduction to solid foods with the gut microbiota, determined by 16S rRNA gene sequencing of stool collected at 5 years of age, and age-and-sex specific BMI-z. We conducted analyses before and after stratifying by breastfeeding duration, and adjusted for delivery mode, gestational age and birth weight., Results: Of the 392 children in the analysis, 109 (27.8%) had early (≤4 months) solids. The association between early (vs later) solids and BMI-z at 5 years was modified by breastfeeding status at 4 months (P = .06). Among children breastfed >4 months, early (vs later) solids were associated with differential relative abundance of 6 bacterial taxa, including lower Roseburia, and 0.30 higher BMI-z (95% CI: 0.05, 0.55) at 5 years. In children breastfed <4 months, early solids were associated with differential relative abundance of 9 taxa, but not with child BMI-z., Conclusions: Early (vs. later) introduction to solid foods in infancy is associated with altered gut microbiota composition and BMI in early childhood, however these associations differ by duration of breastfeeding., (© 2020 World Obesity Federation.)

Background and objectives: We explore the internal and external resources that older adults use to negotiate adversity and related to later life. We investigated the experiences older adults had with adversity and explored the factors that promote and protect resilience and the how these factors shaped the process of managing adversity related to aging. Research design and methods: Semi-structured interviews were conducted with 64 resilient adults ranging in age from 53 to 94 years of age, with an average of 71. Participants were defined as resilient on the basis of their willingness to identify as such. Grounded Theory coding techniques were applied to identify themes reflecting distinct ways in which participants dealt with what they indicated were the most significant hardships and adversities in their lives. Results: What emerged from the narratives about resilience and adversity were accounts of expressions of resilience that reflected the importance in having a resilient identity. Three major themes reflecting psychological and behavioral factors were derived from the data: 1. having vital components of resilience, or behaviors and beliefs in place, that encompass resilience as a way of being; 2. a broad but articulate set of strategies that participants actively engaged with to manage adversity, and 3. a set of protective practices used to prevent risk and prevail in the face of hardship. Discussion and implications: Findings suggest that dealing with adversity in later life requires the use of substantial internal and external resources in what can characterized as a proactive fashion. The results are presented as an interpretation of the participants' perceptions of their resilience and the role it plays in self-concept, strategic planning, and proactive practices. Implications for helping to put resilience into everyday practice are considered.

Background: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children., Methods: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung., Results: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10 - 7 , of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels., Conclusions: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.

Purpose: This study evaluated the safety and efficacy of the JETi8 peripheral thrombectomy system in treating acute deep vein thrombosis (DVT)., Materials and Methods: A retrospective study was conducted in 18 consecutive patients (mean age, 41 years old [range, 15-74 years old]; 5 men and 13 women). There were 21 instances of DVTs (9 iliofemoral, 10 axillosubclavian, and 2 portal), which were treated using the JETi8 thrombectomy device between November 2016 and July 2018. Thrombus was laced with recombinant tissue plasminogen activator (r-TPA) (9.3 mg, on average; range, 2-12 mg) in 17 procedures (81%) prior to thrombectomy. Technical success was defined as restoration of antegrade flow using the JETi8 with or without additional treatment of an underlying obstructive lesion. Procedural success was defined as technical success with or without the addition of overnight catheter-directed thrombolysis (CDT) RESULTS: Mean procedure time was 83 minutes (range, 30-160 minutes), and mean thrombus reduction with the JETi8 alone was 92% (range, 60%-100%). Stent placement was required in 6 procedures (29%). Technical success using the JETi8 system alone was 76% (16 of 21 procedures), whereas 5 procedures (24%) required subsequent overnight CDT in the intensive care unit. Procedural success rate was 100% (20 of 20 procedures). Mean aspirated volume was 531 mL (range, 250-1,230 mL). The only adverse event was a subsegmental pulmonary embolism. Seven patients (33%) were discharged the same day. Recurrent thrombosis was observed in 5 patients (24%), of whom 3 were successfully treated with the JETi8 system., Conclusions: The JETi8 system may be a safe and effective option for thrombectomy of acute DVT., (Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved.)

Importance: Opioid use disorder is increasingly common in the United States and affects many pregnancies. Given the rise in pregnancies complicated by opioid use, providers should understand the diagnosis and management of opioid use disorder in pregnancy., Objective: This article focuses on screening for opioid misuse, selecting appropriate treatment for patients, initiating medication-assisted treatment in the inpatient setting, and providing appropriate peripartum care., Evidence Acquisition: A PubMed search was undertaken using the following search terms: "opioid use disorder", "pregnancy," "medication assisted treatment," "buprenorphine," "methadone," "heroin," "addiction," "neonatal abstinence syndrome," and "detoxification." The search was limited to the English language publications, with most being published after 2000., Results: All women should be screened for opioid use disorder during pregnancy. Opioid use has profound effects on the mother and infant. Medication-assisted treatment is the standard of care for pregnant women with opioid use disorder. Patients will require a multidisciplinary approach to management in the intrapartum and postpartum period., Conclusions: Opioid use disorder is a common, chronic condition with significant implications during pregnancy. Recognition and appropriate treatment of this disorder can optimize maternal and fetal outcomes., Conclusions: Obstetricians are increasingly being challenged to manage pregnancies complicated by opioid use disorder and should be proficient in providing safe and effective care.

The placenta participates in maternal insulin sensitivity changes during pregnancy; however, mechanisms remain unclear. We investigated associations between maternal insulin sensitivity and placental DNA methylation markers across the genome. We analyzed data from 430 mother-offspring dyads in the Gen3G cohort. All women underwent 75-g oral glucose tolerance tests at ∼26 weeks of gestation; we used glucose and insulin measures to estimate insulin sensitivity (Matsuda index). At delivery, we collected samples from placenta (fetal side) and measured DNA methylation using Illumina EPIC arrays. Using linear regression models to quantify associations at 720,077 cytosine-guanine dinucleotides (CpGs), with adjustment for maternal age, gravidity, smoking, BMI, child sex, and gestational age at delivery, we identified 188 CpG sites where placental DNA methylation was associated with Matsuda index ( P < 6.94 × 10 -8 ). Among genes annotated to these 188 CpGs, we found enrichment in targets for miRNAs, in histone modifications, and in parent-of-origin DNA methylation including the H19/MIR675 locus (paternally imprinted). We identified 12 known placenta imprinted genes, including KCNQ1 Mendelian randomization analyses revealed five loci where placenta DNA methylation may causally influence maternal insulin sensitivity, including the maternally imprinted gene DLGAP2. Our results suggest that placental DNA methylation is fundamentally linked to the regulation of maternal insulin sensitivity in pregnancy., (© 2019 by the American Diabetes Association.)

Changes in fetal DNA methylation (DNAm) of the leptin ( LEP ) gene have been associated with exposure to maternal hyperglycemia, but their links with childhood obesity risk are still unclear. We investigated the association between maternal hyperglycemia, placental LEP DNAm (25 5'-C-phosphate-G-3' (CpG) sites), neonatal leptinemia, and adiposity (i.e., BMI and skinfold thickness (ST) (subscapular (SS) + triceps (TR) skinfold measures, and the ratio of SS:TR) at 3-years-old, in 259 mother-child dyads, from Gen3G birth cohort. We conducted multivariate linear analyses adjusted for gestational age at birth, sex of the child, age at follow-up, and cellular heterogeneity. We assessed the causal role of DNAm in the association between maternal glycemia and childhood outcomes, using mediation analysis. We found three CpGs associated with neonatal leptinemia ( p ≤ 0.002). Of these, cg05136031 and cg15758240 were also associated with BMI (β = -2.69, p = 0.05) and fat distribution (β = -0.581, p = 0.05) at 3-years-old, respectively. Maternal glycemia was associated with DNAm at cg15758240 (β = -0.01, p = 0.04) and neonatal leptinemia (β = 0.19, p = 0.004). DNAm levels at cg15758240 mediates 0.8% of the association between maternal glycemia and neonatal leptinemia ( p < 0.001). Our results support that DNAm regulation of the leptin pathway in response to maternal glycemia might be involved in programming adiposity in childhood.

Background: Women with high levels of physical activity (PA) are less likely to develop gestational diabetes mellitus (GDM), but the relations with sleep and sedentary behaviours (SB) are more controversial. We aimed to investigate all three components (sleep, PA, and SB) and their association with maternal glucose in pregnancy., Methods: We included 766 pregnant women recruited at first trimester and that we followed at second trimester. We collected blood samples, anthropometry and standardized questionnaires about lifestyle including PA, SB, and sleep duration at both visits. Women completed a 50 g glucose challenge test at first trimester and 75-g oral glucose tolerance test (OGTT) at second trimester. We conducted regression analyses to test cross-sectional associations between sleep, PA, and SB with maternal glucose levels while taking into account potential confounders (maternal age, pre-pregnancy body mass index (BMI), gravidity, and smoking). We considered linear and quadratic relationships., Results: At first trimester, we observed a linear relationship between shorter sleep duration and higher glucose levels, which was attenuated after adjustments for confounders. At second trimester, we found a quadratic relationship between sleep and glucose showing lowest levels at fasting and 1 h-post OGTT for women who slept 6-10 h/night. This association remained significant after adjusting for confounders and taking into account PA and/or SB. Greater amount of SB was associated with higher 1 h-glucose after adjustment for confounders (β = 0.132; SE = 0.047; P = 0.005)., Conclusions: Sleep duration is associated with glucose regulation in pregnancy, independently of PA and SB, and this association varies according to the period of gestation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The objectives were to assess whether social support for healthy eating and perceived food environment are associated with diet quality, and to investigate if sociodemographic characteristics moderate these associations. A probability sample of French-speaking adults from the Province of Québec, Canada, was recruited in the context of the PREDISE study. Participants reported their perceptions of supportive and non-supportive actions related to healthy eating from close others at home and outside of home ( n = 952), and of the accessibility to healthy foods ( n = 1035). The Canadian Healthy Eating Index (C-HEI) was calculated based on three Web-based 24 h food recalls. Multiple linear regression models showed that supportive (B = 1.50 (95% CI 0.46, 2.54)) and non-supportive (B = -3.06 (95% CI -4.94, -1.18)) actions related to healthy eating from close others at home were positively and negatively associated with C-HEI, respectively, whereas actions from close others outside of home were not. The negative association between non-supportive actions occurring at home and C-HEI was stronger among participants with lower (vs. higher) levels of education ( p interaction = 0.03). Perceived accessibility to healthy foods was not associated with C-HEI ( p > 0.05). These results suggest that the social environment may have a stronger influence on healthy eating than the perceived physical environment. This adds support for healthy eating promotion programs involving entire families, especially for more socioeconomically disadvantaged individuals, whose efforts to eat healthily may be more easily thwarted by non-supportive households.

Compassion fatigue (CF) can be detrimental to health care providers' mental and physical health, efficiency, and quality of patient care. Although many studies explore CF in physicians and nurses, there is currently limited published research regarding how advanced practice registered nurses (APRNs) develop and address CF. APRNs may be at high risk for developing CF due to their work responsibilities, patient interaction, and personal characteristics. Because of its impact on health care providers, patients, and organizations, APRNs should be aware of the potential causes, symptoms, and negative effects of this phenomenon., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Illumina HumanMethylation450 BeadChip (450K) has been commonly used to investigate DNA methylation in human tissues. Recently, it has been replaced by Illumina HumanMethylationEPIC BeadChip (EPIC) covering over 850,000 CpGs distributed genome-wide. Many consortia have now datasets coming from both arrays and aspire to analyze the two together. The placenta shows a high number of intermediate methylation levels and is often investigated for obstetric/birth outcomes, and potentially for long-term programming in offspring. We performed a systematic comparison between the two arrays using 108 duplicate placental samples from Gen3G birth cohort. We find that placenta shows a high per-sample correlation between the arrays, and higher median correlations at individual CpGs than those reported for blood. We identify 26,340 probes with absolute difference in per cent methylation >10%. We conclude that EPIC and 450K placental data can be combined, and we provide two lists of CpGs that should be excluded to avoid misleading results.

Prenatal maternal smoking is a risk factor for lower birth weight. We performed epigenome-wide association analyses of placental DNA methylation (DNAm) at 720,077 cytosine-phosphate-guanine (CpG) sites and prenatal maternal smoking among 441 mother-infant pairs (2010-2014) and evaluated whether DNAm mediates the association between smoking and birth weight using mediation analysis. Mean birth weight was 3,443 (standard deviation, 423) g, and 38 mothers (8.6%) reported smoking at a mean of 9.4 weeks of gestation. Prenatal maternal smoking was associated with a 175-g lower birth weight (95% confidence interval (CI): -305.5, -44.8) and with differential DNAm of 71 CpGs in placenta, robust to latent-factor adjustment reflecting cell types (Bonferroni-adjusted P < 6.94 × 10-8). Of the 71 CpG sites, 7 mediated the association between prenatal smoking and birth weight (on MDS2, PBX1, CYP1A2, VPRBP, WBP1L, CD28, and CDK6 genes), and prenatal smoking × DNAm interactions on birth weight were observed for 5 CpG sites. The strongest mediator, cg22638236, was annotated to the PBX1 gene body involved in skeletal patterning and programming, with a mediated effect of 301-g lower birth weight (95% CI: -543, -86) among smokers but no mediated effect for nonsmokers (β = -38 g; 95% CI: -88, 9). Prenatal maternal smoking might interact with placental DNAm at specific loci, mediating the association with lower infant birth weight., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: The "Life's Simple 7" (LS7) metrics were developed by the American Heart Association (AHA) to assess and promote cardiovascular health in the American population. The purpose of this study was to assess the overall cardiovascular health of French-speaking adults from the Province of Quebec using the LS7 score., Methods and Results: A total of 777 age and sex-representative participants of five different administrative regions in the Province of Quebec (387 men and 390 women; mean age ± SEM: 41.9 ± 0.1 years) were included in these analyses. Metrics of the LS7 score (smoking, physical activity, diet, body mass index, blood pressure, fasting total cholesterol and blood glucose) were analysed to generate a final score ranging from 0 to 7. Only 0.5% of participants met all criteria for ideal cardiovascular health. The diet metric showed the lowest prevalence of "ideal" scores (4.8%) whereas not smoking was the metric with the highest prevalence (88.1%). Women had a higher LS7 score than men, while age and education level (negative and positive association, respectively; p < 0.0001) were also associated with the LS7 score., Conclusion: Consistent with studies conducted among other populations, very few French-speaking adults from the Province of Quebec achieve an ideal cardiovascular health. These data indicate that further public health efforts aimed at promoting the LS7 metrics, focusing primarily on diet, are urgently needed. Specific groups, including older adults and those with lower levels of education, should be targeted when developing cardiovascular health promotion interventions., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Myotonic dystrophy type 1 (DM1) is an autosomal dominant inherited disorder caused by expansion of a germline and somatically unstable CTG repeat in the DMPK gene. Previously, CTG repeat length at birth has been correlated to patient age at symptom onset. Attempts to correlate CTG repeat length with progressive DM1 phenotypes, such as muscle power, have proven difficult. To better correlate genotype with progressive phenotypes, we have measured CTG repeat tract length and screened for interrupting variant repeats in 192 study participants from a well-characterized Canadian cohort. We have assessed genotype-phenotype correlations with nine progressive measures of skeletal muscle power and respiratory function. We have built statistical models that include confounding factors such as sex, age, height and weight to further explain variation in muscle power. Our analysis reveals a strong correlation between DM1 genotype and respiratory function and skeletal muscle power, as part of a complex model that includes additional modulators such as sex, age, height, weight and the presence or absence of interrupting variant repeats. Distal skeletal muscle measurements, such as hand pinch and grip strength, show the strongest correlation with disease genotype. Detailed analysis of CTG repeat length, and incorporation of confounding factors, greatly improves the predictive ability of these models. They reveal a greater genetic influence on individual progressive phenotypes than on age at symptom onset and for clinical trials will help optimize stratification and explain patient variability. They will also help practitioners prioritize assessment of the muscular power measurements that correlate best with disease severity., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Cross-sector collaboration is increasingly relied upon to tackle society's pressing and intractable problems. Chief among societal problems are unfavorable structural and social determinants of health. The ability to positively change these health determinants rests on the collaborative processes and structures of governance across diverse sectors in society. The purpose of this article is to present a conceptual framework that sheds light on the basic requirements of cross-sector collaboration for social change to promote the health of populations. A search for theoretical articles on cross-sector collaboration in the fields of public administration and public health was conducted within the journal databases ABI/INFORM Complete and MEDLINE. This search strategy was supplemented by an internet search of the grey literature for high-profile models of cross-sector collaboration. The conceptual framework builds on previous scholarly work by placing emphasis on five essential conditions for collective impact, and on the pivotal role of collective learning. Collective learning, at the basis of planning and taking action, is at the core of effective cross-sector initiatives, specifically because of its critical role in constantly adapting strategies to changing circumstances and unanticipated situations within complex socio-ecological systems.

Aim: To comprehensively characterize the high-density lipoproteins (HDLs) microtranscriptome and to assess whether it is distinct from that of plasma and different between women and men. Methods: RNA was extracted from ultracentrifugation-purified HDLs and plasma from 17 healthy women and men couples, and libraries were sequenced on a HiSeq2500 platform. Results: On average, 310 ± 64 and 355 ± 31 miRNAs were detected (≥1 read per million) in HDLs and plasma, respectively. A total of 62 and 134 miRNAs were over-represented (e.g., miR-150-5p; fold change = 7.52; p a d j  = 5.41 × 10 -111 ) and under-represented (e.g., miR-22-3p; fold change = -5.28; p adj  = 2.11 × 10 -154 ) in HDLs compared with plasma. These miRNAs were enriched in lipid metabolism and cellular processes-related pathways. Conclusion: HDLs exhibit a sex-independent miRNA profile distinct from that of plasma. These miRNAs may contribute to the HDLs' physiology.

Objective: To assess the effects of dystrophia myotonica protein kinase ( DMPK ) DNA methylation (DNAme) epivariation on muscular and respiratory profiles in patients with myotonic dystrophy type 1 (DM1)., Methods: Phenotypes were assessed with standardized measures. Pyrosequencing of bisulfite-treated DNA was used to quantify DNAme levels in blood from 90 patients with DM1 (adult form). Modal CTG repeat length was assessed using small-pool PCR. The presence of Acil-sensitive variant repeats was also tested., Results: DNAme levels upstream of the CTG expansion (exon and intron 11) were correlated with modal CTG repeat length (r s = -0.224, p = 0.040; r s = -0.317, p = 0.003; and r s = -0.241, p = 0.027), whereas correlations were observed with epivariations downstream of the CTG repeats (r s = 0.227; p = 0.037). The presence of a variant repeat was associated with higher DNAme levels at multiple CpG sites (up to 10% higher; p = 0.001). Stepwise multiple linear regression modeling showed that DNAme contributed significantly and independently to explain phenotypic variability in ankle dorsiflexor (3 CpGs: p = 0.001, 0.013, and 0.001), grip ( p = 0.089), and pinch ( p = 0.028) strengths and in forced vital capacity (2 CpGs: p = 0.002 and 0.021) and maximal inspiratory pressure ( p = 0.012)., Conclusions: In addition to the CTG repeat length, DMPK epivariations independently explain phenotypic variability in DM1 and could thus improve prognostic accuracy for patients.

Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.