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Julie St-Pierre1, Luigi Bouchard2,3, Paul Poirier41Department of Pediatrics, Chicoutimi Hospital, Saguenay, QC, Canada; 2Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC, Canada; 3ECOGENE-21 and Lipid Clinic, Chicoutimi Hospital, Saguenay, QC, Canada; 4Quebec Heart and Lungs Institute, Université Laval, Quebec, QC, CanadaAbstract: The burden of obesity is now well established as a precursor of cardiovascular disease and other disorders. Although better clinical guidelines exist to prevent and treat obesity, the prevalence of obesity among children and adolescents is increasing alarmingly. Primary prevention remains the gold standard to significantly reduce the public health concerns associated with obesity. Traditional cardiovascular disease risk factors (such as dyslipidemia, hypertension, type 2 diabetes) for cardiovascular disease among children and adolescents are known. The scope of this review is thus to discuss new and emerging obesity and associated-disease risk factors. Evaluation of the coronary plaque formation, diastolic dysfunction, carotid intima-media thickness and heart rate variability represent interesting tools with clinical relevance. Beyond these new cardiovascular disease risk factors, recent evidence suggests that a detrimental fetal environment, associated with for example, maternal obesity, insulin resistance, and physical inactivity, imprints fetal metabolic programming via epigenetic mechanisms that predisposes the newborn to obesity and cardiovascular disease later in life. This information may impact on the future management of maternal health, as well as for those high-risk children.Keywords: cardiovascular disease, pediatrics, risk factors

Gadolinium (Gd) metal is of great interest in applications such as contrast-enhanced MRI and magnetic cooling. However, it is generally difficult to produce oxide-free and highly magnetic Gd nanoparticles due to the aggressively reactive nature of Gd with oxygen. Herein, we utilized a nanofabrication route and optimization of experimental conditions to produce highly magnetic airstable oxide-free Gd nanoparticles. The nanobowls displayed the highest saturation magnetization to date for Gd, reaching 226.4 emu/g at 2K. The crystalline composition of Gd is found to affect the observed magnetization values: the higher magnetization is observed for nanoparticles that have a lower content of the paramagnetic face-centered cubic (fcc) phase and a greater content of the ferromagnetic hexagonal close-packed (hcp) phase. The relative fcc content was found to depend on the deposition rate of the Gd metal during the nanofabrication process, thereby correlating with altered magnetization. [ABSTRACT FROM AUTHOR]

In rheumatoid arthritis (RA), only a subset of patients develop irreversible bone destruction. Our aim was to identify a microRNA (miR)‐based osteoclast‐related signature predictive of erosiveness in RA. Seventy‐six adults with erosive (E) or nonerosive (NE) seropositive RA and 43 sex‐ and age‐matched healthy controls were recruited. Twenty‐five miRs from peripheral blood mononuclear cell (PBMC)‐derived osteoclasts selected from RNA‐Seq (discovery cohort) were assessed by qPCR (replication cohort), as were 33 target genes (direct targets or associated with regulated pathways). The top five miRs found differentially expressed in RA osteoclasts were either decreased (hsa‐miR‐34a‐3p, 365b‐3p, 374a‐3p, and 511‐3p [E versus NE]) or increased (hsa‐miR‐193b‐3p [E versus controls]). In vitro, inhibition of miR‐34a‐3p had an impact on osteoclast bone resorption. An integrative network analysis of miRs and their targets highlighted correlations between mRNA and miR expression, both negative (CD38, CD80, SIRT1) and positive (MITF), and differential gene expression between NE versus E (GXYLT1, MITF) or versus controls (CD38, KLF4). Machine‐learning models were used to evaluate the value of miRs and target genes, in combination with clinical data, to predict erosion. One model, including a set of miRs (predominantly 365b‐3p) combined with rheumatoid factor titer, provided 70% accuracy (area under the curve [AUC] 0.66). Adding genes directly targeted or belonging to related pathways improved the predictive power of the model for the erosive phenotype (78% accuracy, AUC 0.85). This proof‐of‐concept study indicates that identification of RA subjects at risk of erosions may be improved by studying miR expression in PBMC‐derived osteoclasts, suggesting novel approaches toward personalized treatment. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Studies have linked maternal pre-pregnancy obesity and hyperglycaemia with metabolic and neurodevelopmental complications in childhood. DNA methylation (DNAm) might enable foetal adaptations to environmental adversities through important gene loci. NEGR1 is involved in both energy balance and behaviour regulation. The aim of this study was to investigate associations between placental DNAm at the NEGR1 gene locus and childhood anthropometric and neurodevelopmental profiles in preschoolers. We analysed 276 mother-child dyads from Gen3G, a prospective birth cohort from Sherbrooke. At 3yo (40.4 ± 3.0 months), we measured body mass index (BMI) and the mothers reported on offspring neurobehavior using the Strengths and Difficulties Questionnaire (SDQ). We quantified DNAm levels at 30 CpGs at the NEGR1 locus using the MethylationEPIC Array in placental biopsies. DNAm at four CpGs located before NEGR1 second exon predicted child's BMI z-score (cg26153364: β=−0.16 ± 0.04; p=0.008, cg23166710: β=0.14 ± 0.08; p=0.03) and SDQ total score (cg04932878: β=0.22 ± 1.0; p= 3.0x10−4, cg16525738: β=−0.14 ± 0.18; p=0.01, cg23166710: β=−0.13 ± 0.36; p= 0.04), explaining 4.2% (p=0.003) and 7.3% (p= 1.3 x 10−4) of BMI-z and SDQ variances. cg23166710 was associated with both childhood phenotypes and correlated with NEGR1 placental expression (r=−0.22, p=0.04), suggesting its possible functional role. Together, maternal metabolic characteristics during pregnancy with NEGR1 DNAm levels explained 7.4% (p=4.2 x 10−4) of BMI-z and 14.2% (p=2.8 x 10−7) of SDQ variance at 3yo. This longitudinal study suggests that placental NEGR1 DNAm is associated with adiposity and neurodevelopment in preschool children and highlights its potential role in their comorbidity. [ABSTRACT FROM AUTHOR]

We describe several numerical methods developed to analyze the behavior of spin polarized liquids in the presence of long-range magnetic dipolar interactions and external field gradients. Two of the methods use a discrete lattice of spins. In the first we calculate the magnetic field from the lattice of spins directly, either in the rotating frame, or in the lab frame. In the second method we include the dipolar fields from linear magnetization gradients analytically and calculate the dipolar fields from higher order gradients in Fourier space, where they are a local function of the magnetization. In the third method the magnetization is expanded in a Taylor series and the dipolar fields are calculated analytically for each term. The results of these calculations are compared to experimental data, in which we use two superconducting quantum interference device magnetometers adjacent to a spherical sample of hyperpolarized liquid 129Xe to detect the evolution of magnetization gradients. In particular, we observe an increase by a factor of 100 of the spin dephasing time in a longitudinal magnetic field gradient due to dipolar interactions of the spins. While each of the numerical techniques has certain limitations, they are generally in agreement with each other and with experimental data. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

para-Hydrogen induced polarization is a technique of magnetic resonance hyperpolarization utilizing hydrogen's para-spin state for generating signal intensities at magnitudes far greater than state-of-the-art magnets. Platinum nanoparticle-catalysts with cysteine-capping are presented. The measured polarization is the highest reported to date in water, paving pathways for generating medical imaging contrast agents. [ABSTRACT FROM AUTHOR]

The requirement for large bulk resistivity in topological insulators has led to the design of complex ternary and quaternary phases with balanced donor and acceptor levels. A common feature of the optimized phases is that they lie close to the p- to n-transition. The tetradymite Bi2Te3-xSex system exhibits minimum bulk conductance at the ordered composition Bi2Te2Se. By combining local and integral measurements of the density of states, we find that the point of minimum electrical conductivity at x = 1.0 where carriers change from hole-like to electron-like is characterized by conductivity of the mixed type. Our experimental findings, which are interpreted within the framework of a two-band model for the different carrier types, indicate that the mixed state originates from different types of native defects that strongly compensate at the crossover point. [ABSTRACT FROM AUTHOR]

Placental lipoprotein lipase (LPL) is crucial for placental lipid transfer. Impaired LPL gene expression and activity were reported in pregnancies complicated by gestational diabetes mellitus (GDM) and intra-uterine growth restriction. We hypothesized that placental LPL DNA methylation is altered by maternal metabolic status and could contribute to fetal programming. The objective of this study was thus to assess whether placental LPL DNA methylation is associated with GDM and both maternal and newborn lipid profiles. Placenta biopsies were sampled at delivery from 126 women including 27 women with GDM diagnosed following a post 75 g-oral glucose tolerance test (OGTT) between weeks 24 and 28 of gestation. Placental LPL DNA methylation and expression levels were determined using bisulfite pyrosequencing and quantitative real-time PCR, respectively. DNA methylation levels within LPL proximal promoter region (CpG1) and intron 1 CpG island (CpGs 2 and 3) were lower in placenta of women with GDM. DNA methylation levels at LPL-CpG1 and CpG3 were also negatively correlated with maternal glucose (2-h post OGTT; r=–0.22; P=0.02) and HDL-cholesterol levels (third trimester of pregnancy; r=–0.20; p=0.03), respectively. Moreover, we report correlation between LPL-CpG2 DNA methylation and cord blood lipid profile. DNA methylation levels within intron 1 CpG island explained up to 26% (r⩽–0.51; P<0.001) of placental LPL mRNA expression variance. Overall, we showed that maternal metabolic profile is associated with placental LPL DNA methylation dysregulation. Our results suggest that site-specific LPL epipolymorphisms in the placenta are possibly functional and could potentially be involved in determining the future metabolic health of the newborn. [ABSTRACT FROM PUBLISHER]

TheDUSP1 gene encodes a member of the dual-specificity phosphatase family previously identified as being differentially expressed in visceral adipose tissue (VAT) of severely obesemen with versus without the metabolic syndrome. Objective. To test the association betweenDUSP1 polymorphisms, obesity-relatedmetabolic complications, gene methylation, and expression levels inVAT. Methods. The DUSP1 locus and promoter region were sequenced in 25 individuals. SNPs were tested for association with obesity-related complications in a cohort of more than 1900 severely obese individuals. The impact of SNPs on methylation levels of 36 CpG sites and correlations between DNA methylation and gene expression levels in VAT were computed in a subset of 14 samples. Results. Heterozygotes for rs881150 had lowerHDL-cholesterol levels (HDL-C; P= 0.01), and homozygotes for theminor allele of rs13184134 and rs7702178 had increased fasting glucose levels (P= 0.04 and 0.01, resp.). rs881150 was associated with methylation levels of CpG sites located ~1250 bp upstream the transcription start site. Methylation levels of 4 CpG sites were inversely correlated with DUSP1 gene expression. Conclusion. These results suggest that DUSP1 polymorphismsmodulate plasma glucose andHDL-C levels in obese patients possibly through alterations of DNA methylation and gene expression levels. [ABSTRACT FROM AUTHOR]

Shear stress is an important physical factor that regulates proliferation, migration, and morphogenesis. In particular, the homeostasis of blood vessels is dependent on shear stress. To mimic this process ex vivo, efforts have been made to seed scaffolds with vascular and other cell types in the presence of growth factors and under pulsatile flow conditions. However, the resulting bioreactors lack information on shear stress and flow distributions within the scaffold. Consequently, it is difficult to interpret the effects of shear stress on cell function. Such knowledge would enable researchers to improve upon cell culture protocols. Recent work has focused on optimizing the microstructural parameters of the scaffold to fine tune the shear stress. In this study, we have adopted a different approach whereby flows are redirected throughout the bioreactor along channels patterned in the porous scaffold to yield shear stress distributions that are optimized for uniformity centered on a target value. A topology optimization algorithm coupled to computational fluid dynamics simulations was devised to this end. The channel topology in the porous scaffold was varied using a combination of genetic algorithm and fuzzy logic. The method is validated by experiments using magnetic resonance imaging readouts of the flow field. Biotechnol. Bioeng. 2012; 109:1844-1854. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Growing evidence suggests that epigenetic profile changes occurring during fetal development in response to in utero environment variations could be one of the mechanisms involved in the early determinants of adult chronic diseases. In this study, we tested whether maternal glycemic status is associated with the adiponectin gene (ADIPOQ) DNA methylation profile in placenta tissue, in maternal circulating blood cells, and in cord blood cells. We found that lower DNA methylation levels in the promoter of ADIPOQ on the fetal side of the placenta were correlated with higher maternal glucose levels during the second trimester of pregnancy (2-h glucose after the oral glucose tolerance test; r(s) ≤ -0.21, P < 0.05). Lower DNA methylation levels on the maternal side of the placenta were associated with higher insulin resistance index (homeostasis model assessment of insulin resistance) during the second and third trimesters of pregnancy (r(s) ≤ -0.27, P < 0.05). Finally, lower DNA methylation levels were associated with higher maternal circulating adiponectin levels throughout pregnancy (r(s) ≤ -0.26, P < 0.05). In conclusion, the ADIPOQ DNA methylation profile was associated with maternal glucose status and with maternal circulating adiponectin concentration. Because adiponectin is suspected to have insulin-sensitizing proprieties, these epigenetic adaptations have the potential to induce sustained glucose metabolism changes in the mother and offspring later in life. [ABSTRACT FROM AUTHOR]

Existing literature indicates peer support is beneficial for people with mental illnesses and plays an important role in recovery. While many studies in the mental health field have focused on formalized peer support within the community, none have explored the experience of peer support among hospitalized patients. The purpose of the current study was to explore the perceptions and experiences of naturally occurring peer support among adult mental health inpatients. In-depth interviews were conducted with ten inpatients across four mental health units, two acute and two long-term. Interviews were transcribed verbatim and analyzed using a qualitative descriptive design. The data show that peer support among inpatients is extensive and beneficial, and occurs independently of staff involvement. The findings illustrate that peer support is a thoughtful process that involves observing, reflecting, taking action, and evaluating outcomes. Supportive actions include helping with activities of daily living, sharing material goods, providing information and advice, sharing a social life, and offering emotional support. This leads to various positive outcomes for providers and recipients of peer support, such as improved mental health outcomes and quality of life. Attempts to provide supportive interactions occur within a particular context, which can hinder or facilitate peer support. The new insights from this study could provide health professionals with an increased recognition of peer support and an appreciation for the unique role patients play in their own and in their peers’ recovery. These findings have important implications for establishing collaborative working partnerships with mental health inpatients. [ABSTRACT FROM AUTHOR]

Shimming systems are required to provide sufficient field homogeneity for high resolution nuclear magnetic resonance (NMR). In certain specialized applications, such as rotating-field NMR and mobile ex situ NMR, permanent magnet-based shimming systems can provide considerable advantages. We present a simple two-dimensional shimming method based on harmonic corrector rings which can provide arbitrary multipole order shimming corrections. Results demonstrate, for example, that quadrupolar order shimming improves the linewidth by up to an order of magnitude. An additional order of magnitude reduction is in principle achievable by utilizing this shimming method for z-gradient correction and higher order xy gradients. [ABSTRACT FROM AUTHOR]

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. Copyright © 2004 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

The discovery linking the genes BRCA1&2 to familial breast cancer played an important role in the clinical practice of geneticists and physicians. The availability of genetic tests for BRCA gene mutations prompted cancer geneticists to give information about genetic risk and to assess many women with a personal or family history of breast or ovarian cancer to inform them of preventive measures. These consist mainly of breast self-examination, mammography screening, chemoprevention and prophylactic surgery (mastectomy, oophorectomy). This paper examines clinical practices related to hereditary breast cancer testing and introduces a number of results from a survey carried out, between 1996 and 1998, in three clinics located in Montreal (Quebec, Canada), Marseilles (France) and Manchester (Great Britain). Results show substantial differences in the way cancer geneticists deal with environmental risk factors, breast and ovarian cancer testing, and chemoprevention and prophylactic surgery. Differences across cities persist in the multivariate analysis, suggesting that attitudes towards preventive measures may be partially explained by cultural factors. Different dimensions of culture are discussed including the social representation of health and risk, the interpretation of scientific evidence and the role of innovation leadership. [ABSTRACT FROM AUTHOR]