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Background: Evidence exists that maternal antenatal depression may have adverse impacts on perinatal outcomes. However, the results of those studies are inconsistent and mainly focus on maternal depressive symptoms in the second or third trimester., Methods: This prospective cohort study used a sub-sample of participants from the Sino-Canadian Healthy Life Trajectories Initiative trial. The Edinburgh Postnatal Depression Scale (EPDS) was used to screen for depressive symptoms in the first, second, and third trimesters, respectively. Infant growth indicator measurements were conducted in the first year of life. Logistic regression, Spearman correlation analyses and Generalized estimation equation (GEE) models were used to test the hypotheses., Results: 2053 participants were recruited in this study, 326 of whom had at least one EPDS score ≥ 10 during pregnancy. A higher EPDS score in the first (aOR=1.053, 95 % CI: 1.004-1.103) or in the second trimester (aOR=1.060, 95 % CI: 1.007-1.115) was associated with greater risk of macrosomia. A higher EPDS score in the third trimester was associated with higher risks of preterm birth (aOR=1.079, 95 % CI: 1.006-1.157) and the infant being small for gestational age (aOR=1.097, 95 % CI: 1.015-1.185). GEE models showed that a greater EPDS score in the third trimester was associated with higher infant subscapular skinfold thickness (adjusted β=0.026, 95 % CI: 0.003-0.050)., Conclusion: Maternal depressive symptoms in different trimesters were differentially associated with infant weight and growth parameters at birth and postnatally. The present study further highlights the importance of depression screening in all trimesters of pregnancy, including the first trimester., Competing Interests: Declaration of Competing Interest The authors of this article declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Abetalipoproteinemia (ABL) is a rare recessive genetic disease caused by bi-allelic pathogenic variants in the microsomal triglyceride transfer protein (MTTP) gene. This disease is characterized by a deficiency in the secretion of apolipoprotein B-containing lipoproteins. Patients with ABL present with neurological, hematological, and gastrointestinal symptoms due to fat malabsorption and a deficiency in liposoluble vitamins. In this report, we present a total of four ABL cases, including three new cases, all originating from the same French-Canadian founder population in Saguenay-Lac-Saint-Jean, Québec, Canada. These individuals are homozygous for the same pathogenic variant in the MTTP gene (c.419dup, p.Asn140Lysfs*2). We found that this variant is more common than anticipated in this population, with an estimated carrier frequency of 1:203. Early diagnosis is essential to initiate treatment known to prevent complications associated with ABL. Population carrier screening or newborn screening for ABL should be considered in this French-Canadian founder population., Competing Interests: Declaration of competing interest AB received research grants from Akcea, Amgen, Astra Zeneca, Fondation Leducq, Fondation Yvan Morin, Merck Frosst, and Sanofi. He has participated in clinical research protocols from Acasti Pharma Inc., Akcea, Amgen, Arrowhead Pharmaceuticals, Astra Zeneca, Ionis Pharmaceuticals, Inc., ISIS Pharmaceuticals, The Medicines Company, Merck Frosst, Novartis, Pfizer, Regeneron Pharmaceuticals Inc., and Sanofi. He has served on advisory boards and received honoraria for symposia from Akcea, Amgen, and Sanofi. SPG, MP, LG, GG, VD, VP, and LB have no conflict of interest to declare., (Copyright © 2024. Published by Elsevier Inc.)

Background: Multifactorial chylomicronemia syndrome (MCS) is a severe form of hypertriglyceridemia associated with an increased risk of acute pancreatitis (AP). The risk of AP is heterogenous and is associated with increased level of triglycerides (TG) and presence of rare variants in TG metabolism-related genes., Objective: To determine if the accumulation of common variants in pancreatitis susceptibility genes, measured with a weighted polygenic risk score (PRS), is associated with AP in MCS patients., Methods: A total of 114 patients with MCS underwent genetic testing for eight single nucleotide polymorphisms (SNPs) in known pancreatitis susceptibility genes (ABCG8, CLDN2, CTRB1/2, CTRC, PRSS1, PRSS2, SPINK1 and TWIST2). A weighted PRS was calculated to account for the phenotypic effect of each SNP locus., Results: A high pancreatitis-PRS score (≥ 0.44) was associated with a 2.94-fold increase risk of AP (p = 0.02) among patients with MCS. MCS patients with a high pancreatitis-PRS and a rare variant in TG metabolism-related gene have a 9.50-fold increase risk of AP (p = 0.001), compared to those with a low-PRS and no rare variant. A multivariate analysis including the presence of rare variants, the maximal TG values and a high pancreatitis-PRS explained 26% of the variability in AP in MCS patients., Conclusion: This study shows for the first time that the accumulation of common variants in pancreatitis susceptibility genes is associated with AP in MCS patients. Pancreatitis-PRS could help clinicians to identify MCS patients who may be at higher risk of AP and who may benefit from more aggressive treatment., Competing Interests: Declaration of competing interest AB received research grants from Akcea, Amgen, Astra Zeneca, Fondation Leducq, Fondation Yvan Morin, Merck Frosst, and Sanofi. He has participated in clinical research protocols from Acasti Pharma Inc., Akcea, Amgen, Arrowhead Pharmaceuticals, Astra Zeneca, Ionis Pharmaceuticals, Inc., ISIS Pharmaceuticals, The Medicines Com- pany, Merck Frosst, Novartis, Pfizer, Regeneron Pharmaceu- ticals Inc., and Sanofi. He has served on advisory boards and received honoraria for symposia from Akcea, Amgen, and Sanofi. SB received research grants from Akcea, Fondation Leducq, and Fondation Yvan Morin. She has participated in clinical research protocols from Akcea, Amgen, Ionis Pharmaceuticals, Inc., The Medicines Company, Novartis, Pfizer, and Sanofi. She has served on advisory boards for Akcea, Amgen, HLS Therapeutics, Novartis, Novo Nordisk, and Sanofi, and received honoraria for symposia from Akcea, Amgen, Novo Nordisk, and Sanofi. SPG, MP, LB, VD and AT have nothing to declare., (Copyright © 2024. Published by Elsevier Inc.)

Background and Aims: Multifactorial chylomicronemia syndrome (MCS) is a severe form of hypertriglyceridemia (hyperTG) associated with an increased risk of acute pancreatitis (AP). Severe hyperTG is mainly polygenic in nature, either caused by the presence of heterozygous pathogenic variants (PVs) in TG-related metabolism genes or by accumulation of common variants in hyperTG susceptibility genes. This study aims to determine if the risk of AP is similar amongst MCS patients with different molecular causes of severe hyperTG., Methods: This study included 114 MCS patients who underwent genetic testing for PVs in TG-related metabolism genes and 16 single nucleotide polymorphisms (SNPs) in hyperTG susceptibility genes. A weighted TG-polygenic risk score (TG-PRS) was calculated. A TG-PRS score ≥ 90th percentile was used to define a high TG-PRS., Results: Overall, 66.7% of patients had severe hyperTG of polygenic origin. MCS patients with only a PV and those with both a PV and high TG-PRS were more prone to have maximal TG concentration ≥ 40 mmol/L (OR 5.33 (1.55-18.36); p = 0.008 and OR 5.33 (1.28-22.25); p = 0.02), as well as higher prevalence of AP (OR 3.64 (0.89-14.92); p = 0.07 and OR 11.90 (2.54-55.85); p = 0.002) compared to MCS patients with high TG-PRS alone., Conclusions: This is the first study to show that MCS caused by a high TG-PRS and a PV is associated with higher risk of AP, similar to what is seen in the monogenic form of severe hyperTG. This suggests that determining the molecular cause of severe hyperTG could be useful to stratify the risk of pancreatitis in MCS., Competing Interests: Declaration of competing interest AB received research grants from Akcea, Amgen, Astra Zeneca, Fondation Leducq, Fondation Yvan Morin, Merck Frosst, and Sanofi. He has participated in clinical research protocols from Acasti Pharma Inc., Akcea, Amgen, Arrowhead Pharmaceuticals, Astra Zeneca, Ionis Pharmaceuticals, Inc., ISIS Pharmaceuticals, The Medicines Company, Merck Frosst, Novartis, Pfizer, Regeneron Pharmaceuticals Inc., and Sanofi. He has served on advisory boards and received honoraria for symposia from Akcea, Amgen, and Sanofi. SB received research grants from Akcea, Fondation Leducq, and Fondation Yvan Morin. She has participated in clinical research protocols from Akcea, Amgen, Ionis Pharmaceuticals, Inc., The Medicines Company, Novartis, Pfizer, and Sanofi. She has served on advisory boards for Akcea, Amgen, HLS Therapeutics, Novartis, Novo Nordisk, and Sanofi, and received honoraria for symposia from Akcea, Amgen, Novo Nordisk, and Sanofi. SPG, MP, LB, LG, VD and AT have nothing to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Carrier couples of recessive diseases face an important decision-making process regarding their familial planning that can become a significant source of discomfort and potential regrets. To date, no study has described the decisional needs of carrier couples of Leigh syndrome French-Canadian type, hereditary tyrosinemia type 1, hereditary motor and sensory neuropathy with or without agenesis of the corpus callosum and autosomal recessive spastic ataxia of Charlevoix-Saguenay undergoing family planning decision-making process. Our study aimed to describe the decisional needs of carrier couples according to the Ottawa Decision Support Framework., Methods: A qualitative descriptive study was conducted. Qualitative individual and joint couple interviews were performed among 39 carrier individuals and 11 health and social care professionals., Results: Carrier couples' decision-making process is complex, and their decisional needs include, among others, sufficient knowledge about the disease and the reproductive options, personal values and available support. Increased decisional conflict was observed among carriers of diseases associated with low morbidity and mortality., Conclusion: Family planning decision-making is an evolutive deliberative process that requires appropriate shared decision-making to insure decisional comfort., Practice Implications: Carrier couples family planning decision-making process needs to be better supported., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

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.)

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.)

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.)

Background: Regular monitoring of the population's food and nutrient intake is essential to develop effective nutrition-focused public health policies. The aim of this study was to provide dietary intake estimates using an age- and sex-representative sample of French-speaking adults with Internet access from 5 administrative regions in the province of Quebec, Canada., Methods: PRÉDicteurs Individuels, Sociaux et Environnementaux (PREDISE) is a multicentre cross-sectional study that used a Web-based approach to collect individual, social, and environmental data on factors associated with adherence to dietary recommendations. Dietary intake was estimated from the average of 3 validated Web-based 24-hour recalls., Results: Mean (± SD) age of the 1147 participants (50.2% women) was 43.2 ± 4.6 years and median body mass index was 26.3 (interquartile range, 23.3-30.3). Less than 25% of participants met Canada's Food Guide recommendations for vegetables and fruit intake (prevalence, 23.6%; 95% confidence interval [CI], 21.1-26.0). Most participants reported consuming more than 2300 mg of sodium (prevalence, 80.5%; 95% CI, 78.2-82.7) and more than 10% energy as saturated fats (prevalence, 74.2%; 95% CI, 71.6-76.7). Mean Canadian Healthy Eating Index score on a scale of 0-100 was 54.5 (95% CI, 53.8-55.2), reflecting relatively poor diet quality according to current dietary recommendations., Conclusions: Self-reported dietary intakes measured using a new validated Web-based 24-hour recall in this sample of French-speaking adults from Quebec and with access to Internet suggest low adherence to current Canadian dietary guidelines. These data emphasize the need for more effective nutrition-focused public health policies to maximize cardiovascular disease prevention at the population level., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

The intimate and sexual dimension of future and new parenting couples' relationship is the most affected and the most vulnerable during the transition to parenthood; couples must adapt to support their relationship and their families. The purpose of this scoping review is to identify the literature that has been published on perinatal sexuality in the last 15 years. A total of 123 empirical articles were selected. This first article of a series of two is about sexuality during pregnancy. In addition to painting a picture from the chosen articles, 23 prenatal sexual variables were analyzed. The combined data present a diversified portrait of perinatal sexuality during pregnancy: the intimate and sexual experience varies during this period. Despite some exceptions, a certain tendency towards a gradual and progressive decline in most sexual behaviors and overall sexual expression during pregnancy was noted, with a marked decrease in early pregnancy and during the third trimester. Women are particularly affected by a greater number of sexual changes, but men are too. Many simultaneous physiological and psychological factors affect the sexual expression of the couples. Sexual fluctuations are a natural phenomenon during the transition to parenthood; couples must adjust to the new conditions and to the changes associated with sexuality during pregnancy, which are considered temporary. Sexoperinatal interventions should be a part of holistic perinatal health care in order to help couples maintain an intimate relationship and a healthy and positive sexual life., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The intimate and sexual dimension of future and new parenting couples' relationship is the most affected and the most vulnerable during the transition to parenthood. The purpose of this scoping review is to present the portrait of perinatal sexuality through 123 empirical articles published in the last 15 years. This second article in a series of two is about sexuality during labor and birth, during the postpartum, and in relation to breastfeeding. A total of 29 sexual variables were analyzed. Sexuality during the intrapartal and postnatal periods is very diversified. Some recurring items, however, can be identified: a period of non-sexuality in the first postnatal months, followed by a gradual return of sexuality from 3 to 6 months postpartum and continuing until 12 months or more. Sexuality during the intrapartum is considered taboo and couples' experiences can be at opposite ends: some couples' experiences are sensual and erotic during childbirth, while others experience birth trauma with a negative sexual impact postnatally. Sexuality during breastfeeding is also taboo with a negative impact on women's sexuality. In all of these circumstances, women's and men's sexuality are affected and a multitude of simultaneous physiological and psychological factors affect their experiences. Fluctuations in the intimate and sexual dimensions of the conjugal relationship are considered as a natural phenomenon but temporary. Sexoperinatal interventions should be part of holistic perinatal health care in order to help couples maintain a positive intimate and sexual relationship., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Objective: The objective of this study was to evaluate the safety and efficacy of external beam radiation (EBR) in preventing restenosis after superficial femoral artery (SFA) stenting in comparison with a control group treated with SFA stenting only., Methods: In this Institutional Review Board-approved study, patients who provided written informed consent were randomly assigned to 0 Gy or 14 Gy of EBR to the stent site 24 hours after SFA stenting. The primary end point was the angiographic binary restenosis rate 2 years after stenting. Categorical and continuous end points were respectively analyzed using logistic regression models and Wilcoxon tests. End points expressed as time to event were analyzed using a log-rank test., Results: The study included 155 patients, 46 women and 109 men (mean age, 66 years; range, 45-85 years). In the 0 and 14 Gy groups, binary restenosis was present, respectively, in 44% (34/77) and 68% (52/76; P = .003) 2 years after stenting. Stent thrombosis occurred in 13% (10/78) of the 0 Gy group and in 33% (25/77) of the 14 Gy group (P = .003). Target lesion revascularization at 2 years was 26% (25/78) in the 0 Gy group and 30% (23/77) in the 14 Gy group (P = .56). There were no significant differences in total walking distances change from baseline to 2 years (46 ± 100 and 26 ± 79 m, respectively, in the 0 Gy and 14 Gy group; P = .25). There were no procedure-related deaths and no major amputations., Conclusions: A single 14 Gy dose of EBR to the SFA stenting site did not prevent in-stent restenosis., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Excessive gestational weight gain (GWG) is associated with increased birth weight and neonatal adiposity. However, timing of excessive GWG may have a differential impact on birth outcomes. The objective of this study was to compare the effect of early and mid/late excessive GWG on newborn anthropometry in the context of the Canadian clinical recommendations that are specific for first trimester and for second/third trimesters based on maternal pre-pregnancy BMI., Methods: We included 607 glucose-tolerant women in our main analyses, after excluding women who had less than the recommended total GWG. Maternal body weight was measured in early pregnancy, mid-pregnancy, and late pregnancy. Maternal and fetal clinical outcomes were collected, including newborn anthropometry. Women were divided into four groups according to the Canadian guidelines for GWG in the first and in the second/third trimesters: (1) "overall non-excessive" (reference group); (2) "early excessive GWG"; (3) "mid/late excessive GWG"; and (4) "overall excessive GWG." Differences in newborn anthropometry were tested across GWG categories., Results: Women had a mean (±SD) pre-pregnancy BMI of 24.7 ± 5.2 kg/m(2) and total GWG of 15.3 ± 4.4 kg. Women with mid/late excessive GWG gave birth to heavier babies (gestational age-adjusted birth weight z-score 0.33 ± 0.91) compared with women in the reference group (0.00 ± 0.77, P = 0.007), whereas women with early excessive GWG gave birth to babies of similar weight (gestational age-adjusted z-score 0.01 ± 0.86) to the reference group (0.00 ± 0.77, P = 0.84). When we stratified our analyses and investigated women who gained within the recommendations for total GWG, mid/late excessive GWG specifically was associated with greater newborn size, similar to our main analyses., Conclusion: Excessive GWG in mid/late pregnancy in women who did not gain weight excessively in early pregnancy is associated with increased birth size, even in those who gained within the Canadian recommendations for total GWG., (Copyright © 2016. Published by Elsevier Inc.)

Background: Recent findings suggest that DNA methylation, a well-known epigenetic mechanism, is involved in high-density lipoprotein cholesterol (HDL-C) metabolism and increased cardiovascular disease risk. The aim of this study was thus to assess whether DNA methylation within key genes of lipoprotein metabolism is associated with blood lipid profile variability., Methods and Results: Ninety-eight untreated familial hypercholesterolaemia patients (61 men and 37 women) were recruited for leucocyte DNA methylation analyses at the LDLR, CETP, LCAT and LPL gene promoter loci using bisulfite pyrosequencing. LPL DNA methylation was correlated with HDL-C (r = 0.22; p = 0.031) and HDL particle size (r = 0.47, p = 0.013). In both sex, CETP DNA methylation was negatively associated with low-density lipoprotein cholesterol levels (r < -0.32; p < 0.05). In men, CETP DNA methylation was associated with HDL-C (r = -0.36; p = 0.006), HDL-triglyceride levels (r = 0.59; p < 0.001) and HDL particle size (r = -0.44, p = 0.019). In visceral adipose tissue from 30 men with severe obesity, the associations between LPL DNA methylation, HDL-C (r = -0.40; p = 0.03) and LPL mRNA levels (r = -0.61, p < 0.001) were confirmed., Conclusion: CETP and LPL DNA methylation levels are associated with blood lipid profile, suggesting that further studies of epipolymorphisms should most certainly contribute to a better understanding of the molecular bases of dyslipidemia., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

An internal thoracic artery pseudoaneurysm associated with an arteriovenous fistula to the innominate vein is a very rare complication after implantation of a cardioverter-defibrillator. We report the successful endovascular management of this unusual complication., (Copyright © 2011 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Caloric restriction is recommended for the treatment of obesity, but it is generally characterized by large interindividual variability in responses. The factors affecting the magnitude of weight loss remain poorly understood. Epigenetic factors (ie, heritable but reversible changes to genomic function that regulate gene expression independently of DNA sequence) may explain some of the interindividual variability seen in weight-loss responses., Objective: The objective was to determine whether epigenetics and gene expression changes may play a role in weight-loss responsiveness., Design: Overweight/obese postmenopausal women were recruited for a standard 6-mo caloric restriction intervention. Abdominal subcutaneous adipose tissue biopsy samples were collected before (n = 14) and after (n = 14) intervention, and the epigenomic and transcriptomic profiles of the high and low responders to dieting, on the basis of changes in percentage body fat, were compared by using microarray analysis., Results: Significant DNA methylation differences at 35 loci were found between the high and low responders before dieting, with 3 regions showing differential methylation after intervention. Some of these regions contained genes known to be involved in weight control and insulin secretion, whereas others were localized in known imprinted genomic regions. Differences in gene expression profiles were observed only after dieting, with 644 genes being differentially expressed between the 2 groups. These included genes likely to be involved in metabolic pathways related to angiogenesis and cerebellar long-term depression., Conclusions: These data show that both DNA methylation and gene expression are responsive to caloric restriction and provide new insights about the molecular pathways involved in body weight loss as well as methylation regulation during adulthood.

Background: Obesity is frequently associated with eating disorders, and evidence indicates that both conditions are influenced by genetic factors. However, little is known about the genes influencing eating behaviors., Objective: The objective was to identify genes associated with eating behaviors., Design: Three eating behaviors were assessed in 660 adults from the Quebec Family Study with the use of the Three-Factor Eating Questionnaire. A genome-wide scan was conducted with a total of 471 genetic markers spanning the 22 autosomes to identify quantitative trait loci for eating behaviors. Body composition and macronutrient and energy intakes were also measured., Results: Four quantitative trait loci were identified for disinhibition and susceptibility to hunger. Of these, the best evidence of linkage was found between a locus on chromosome 15q24-q25 and disinhibition (P <0.0058) and susceptibility to hunger (P <0.0001). After fine-mapping, the peak linkage was found between markers D15S206 and D15S201 surrounding the neuromedin beta (NMB) gene. A missense mutation (p.P73T) located within the NMB gene showed significant associations with eating behaviors and obesity phenotypes. The T73T homozygotes were 2 times as likely to exhibit high levels of disinhibition (odds ratio: 1.8; 95% CI: 1.07, 2.89; P=0.03) and susceptibility to hunger (odds ratio: 1.9; 95% CI: 1.15, 3.06; P=0.01) as were the P73 allele carriers. Six-year follow-up data showed that the amount of body fat gain over time in T73T subjects was >2 times that than in P73P homozygotes (3.6 compared with 1.5 kg; P <0.05)., Conclusion: The results suggest that NMB is a very strong candidate gene of eating behaviors and predisposition to obesity.

Human osteoblast-like cells (hOB) stimulated by monosodium urate monohydrate (MSUM) or calcium pyrophosphate dihydrate (CPPD) microcrystals produce the neutrophil chemoattractant IL-8. We investigated whether human neutrophils can adhere to hOB and respond to hOB preactivated by MSUM, CPPD, or by f-Met-Leu-Phe (fMLP). Confluent hOB were coincubated with human blood neutrophils in the presence of MSUM, CPPD or fMLP. MSUM, CPPD, and fMLP stimulated a significant adherence of neutrophils to hOB after a 1h incubation. This effect was not abrogated by pretreating the cells with an anti-CD18 mAb. MSUM stimulated more efficiently the adherence of neutrophils to non-preactivated hOB while CPPD were more efficient when hOB were preactivated. Crystal-free conditioned media from MSUM- or CPPD-stimulated hOB mobilized intracellular free calcium in human neutrophils. Thus, microcrystals were powerful promoters of neutrophil adherence to hOB via a CD18-independent mechanism. The bacterial peptide fMLP also stimulated the adherence of neutrophils to hOB. Functional neutrophil-hOB interactions could be important in bone pathophysiology of crystal- or infection-associated arthritis.

This work presents a model describing the rate of recombination between homologous segments of DNA stably integrated into the genome of cultured cells. The model has been applied to rat cell lines carrying the polyomavirus middle T oncogene and a functional origin of viral DNA replication. Introduction of the gene coding for the polyoma large T antigen or the SV40 large T antigen into cells by DNA transfection promotes homologous recombination in the resident viral inserts with rates varying between 0.1 x 10(-3) and 3.7 x 10(-1) per cell generation.