Assessment of the American Heart Association's "Life's simple 7" score in French-speaking adults from Québec.

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.

Maternal and fetal genetic contribution to gestational weight gain.

BACKGROUND: Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG. PARTICIPANTS AND METHODS: A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight). RESULTS: Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10-8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG. CONCLUSIONS: We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.

A polymorphism of the interferon-gamma-inducible protein 30 gene is associated with hyperglycemia in severely obese individuals.

A previous expression profiling of visceral adipose tissue (VAT) revealed that the immune response gene interferon-gamma-inducible protein 30 (IFI30) gene was 1.72-fold more highly expressed in non-diabetic severely obese men with the metabolic syndrome as compared to those without. Given the importance of low-grade inflammation in obesity-related metabolic complications, we hypothesized that variants in the IFI30 gene are associated with cardiovascular disease (CVD) risk factors. A detailed genetic investigation was performed at the IFI30 locus by sequencing its promoter, exons and intron-exon junction boundaries using DNA of 25 severely obese men. Among the 21 sequence-derived single-nucleotide polymorphisms (SNPs), 5 tagged SNPs (covering 100% of the common SNPs identified) were genotyped in two independent samples of severely obese patients (total n = 1,283). Using a multistage experimental design, chi-square analyses and logistic regressions were performed to compare genotype frequencies and compute odds-ratios (OR) for low and high CVD risk groups (dyslipidemia, hyperglycemia/diabetes and hypertension). A significant association was observed with the non-synonymous SNP rs11554159 (p.R76Q), where GA individuals showed lower risk (OR = 0.67; P = 0.0009) for hyperglycemia/diabetes as compared to homozygotes for the major allele (GG). No association was observed between rs11554159 and VAT IFI30 mRNA levels (P = 0.81), and the expression levels were not correlated with fasting plasma glucose levels (P = 0.31) in 112 non-diabetic severely obese women. The localization of rs11554159 near the active site of IFI30 suggests a functional effect of this SNP. This study showed a novel association between rs11554159 (p.R76Q) polymorphism at the IFI30 locus and the risk of hyperglycemia/diabetes in severely obese individuals.

Macro-scale topology optimization for controlling internal shear stress in a porous scaffold bioreactor.

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.

Remote detection of nuclear magnetic resonance with an anisotropic magnetoresistive sensor.

We report the detection of nuclear magnetic resonance (NMR) using an anisotropic magnetoresistive (AMR) sensor. A "remote-detection" arrangement was used in which protons in flowing water were prepolarized in the field of a superconducting NMR magnet, adiabatically inverted, and subsequently detected with an AMR sensor situated downstream from the magnet and the adiabatic inverter. AMR sensing is well suited for NMR detection in microfluidic "lab-on-a-chip" applications because the sensors are small, typically on the order of 10 mum. An estimate of the sensitivity for an optimized system indicates that approximately 6 x 10(13) protons in a volume of 1,000 mum(3), prepolarized in a 10-kG magnetic field, can be detected with a signal-to-noise ratio of 3 in a 1-Hz bandwidth. This level of sensitivity is competitive with that demonstrated by microcoils in superconducting magnets and with the projected sensitivity of microfabricated atomic magnetometers.

CD19 is functionally and physically associated with surface immunoglobulin.

The pan-B and B cell-specific sIg and CD19 antigens are functionally and physically associated in the presence of anti-Ig mAb. Incubation of B cells with anti-Ig antibodies causes rapid, specific, reversible, concentration-dependent, and unidirectional comodulation of CD19 on every mature B cell studied. Comodulation is produced by mAbs specific for the gamma, mu, kappa, and lambda chains of Ig, and by at least one idiotype-specific mAb. Comodulation is observed using 15 CD19-specific mAbs that detect at least three different CD19 epitopes. Of 18 surface antigens studied, only CD19 is comodulated. Loss of sIg and CD19 occurs concurrently during anti-Ig modulation and demonstrates a comparable dependence on anti-Ig concentration, suggesting that these are parallel rather than serial events. Incubation with anti-Ig specifically cocaps and suggests internalization of anti-CD19 mAb. Comodulation of sIg and CD19 by anti-Ig but not anti-CD19 mAbs suggests that ligand binding enables sIg to then interact with CD19. We propose that CD19 is a component of the B cell antigen receptor and suggest that it could facilitate signal transduction by sIg-antigen complexes.

Temperature dependence of the nitrogen-vacancy magnetic resonance in diamond.

The temperature dependence of the magnetic-resonance spectra of nitrogen-vacancy (NV-) ensembles in the range of 280-330 K was studied. Four samples prepared under different conditions were analyzed with NV- concentrations ranging from 10 ppb to 15 ppm. For all samples, the axial zero-field splitting (ZFS) parameter D was found to vary significantly with temperature, T, as dD/dT=-74.2(7) kHz/K. The transverse ZFS parameter E was nonzero (between 4 and 11 MHz) in all samples, and exhibited a temperature dependence of dE/(EdT)=-1.4(3)x10{-4} K-1. The results might be accounted for by considering local thermal expansion. The temperature dependence of the ZFS parameters presents a significant challenge for diamond magnetometers and may ultimately limit their bandwidth and sensitivity.

Placental NEGR1 DNA methylation is associated with BMI and neurodevelopment in preschool-age children.

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: ß=-0.16 ± 0.04; p=0.008, cg23166710: ß=0.14 ± 0.08; p=0.03) and SDQ total score (cg04932878: ß=0.22 ± 1.0; p= 3.0x10-4, cg16525738: ß=-0.14 ± 0.18; p=0.01, cg23166710: ß=-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.

Multipole shimming of permanent magnets using harmonic corrector rings.

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.

[What do we know about perinatal sexuality? A scoping review on sexoperinatality - part 1]. / Que savons-nous sur la sexualité périnatale ? Un examen de la portée sur la sexopérinatalité ­ partie 1.

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.

[What do we know about perinatal sexuality? A scoping review on sexoperinatality - Part 2]. / Que savons-nous sur la sexualité périnatale ? Un examen de la portée sur la sexopérinatalité ­ Partie 2.

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.

Surface ligand-directed pair-wise hydrogenation for heterogeneous phase hyperpolarization.

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.

Polyoma large T can activate middle T expression by a hit-and-run mechanism.

We studied the activation of polyoma middle T expression in revertant cells carrying transcriptionally inactive copies of the middle T (pmt) oncogene. Introduction of polyoma large T with neo into a rat cell line containing multiple copies of pmt stably integrated into the genome corrected the transformation defect in some of the transfected cells by activating the resident pmt gene. However, once the cells were transformed, continuous expression of the large T protein was not required for the maintenance of pmt expression and hence the maintenance of the transformed state. Transformants arising spontaneously as well as those induced by large T exhibited frequent rearrangements of the pmt inserts. Our results suggest that large T activated pmt expression by a hit-and-run mechanism involving recombination of sequences in the viral insert.

Effect of CpG-rich sequences in transformation and tumorigenesis by polyomavirus.

To address the question of the role of CpG-rich sequences in gene expression, we investigated the effect of an HTF island on the activity of the polyomavirus middle T (pmt) oncogene. pmt is less transformant and less tumorigenic when it is introduced into cultured cells or newborn rats in the presence of an HTF island. Transformed cells carrying pmt in the vicinity of the HTF island have a propensity to revert at a relatively high rate of about 2 X 10(-3) per cell per generation by a mechanism probably involving methylation of some CpG sites in the island. Our results suggest that HTF islands can function as transcriptional silencers.

Hyperpolarization of amino acid derivatives in water for biological applications.

We report on the successful synthesis and hyperpolarization of N-unprotected α-amino acid ethyl propionate esters and extensively, on an alanine derivative hyperpolarized by PHIP (4.4 ± 1.0% 13C-polarization), meeting required levels for in vivo detection. Using water as solvent increases biocompatibility and the absence of N-protection is expected to maintain biological activity.

Mendelian randomization supports causality between maternal hyperglycemia and epigenetic regulation of leptin gene in newborns.

Leptin is an adipokine that acts in the central nervous system and regulates energy balance. Animal models and human observational studies have suggested that leptin surge in the perinatal period has a critical role in programming long-term risk of obesity. In utero exposure to maternal hyperglycemia has been associated with increased risk of obesity later in life. Epigenetic mechanisms are suspected to be involved in fetal programming of long term metabolic diseases. We investigated whether DNA methylation levels near LEP locus mediate the relation between maternal glycemia and neonatal leptin levels using the 2-step epigenetic Mendelian randomization approach. We used data and samples from up to 485 mother-child dyads from Gen3G, a large prospective population-based cohort. First, we built a genetic risk score to capture maternal glycemia based on 10 known glycemic genetic variants (GRS10) and showed it was an adequate instrumental variable (ß = 0.046 mmol/L of maternal fasting glucose per additional risk allele; SE = 0.007; P = 7.8 × 10(-11); N = 467). A higher GRS10 was associated with lower methylation levels at cg12083122 located near LEP (ß = -0.072 unit per additional risk allele; SE = 0.04; P = 0.05; N = 166). Direction and effect size of association between the instrumental variable GRS10 and methylation at cg12083122 were consistent with the negative association we observed using measured maternal glycemia. Lower DNA methylation levels at cg12083122 were associated with higher cord blood leptin levels (ß = -0.17 log of cord blood leptin per unit; SE = 0.07; P = 0.01; N = 170). Our study supports that maternal glycemia is part of causal pathways influencing offspring leptin epigenetic regulation.

Transfer of mlt mutations into polyomavirus intronless genomes by intramolecular recombination in bacteria.

We describe a modification of the procedure of Weber and Weissmann [Nucl. Acids Res. 11 (1983) 5661-5669] for the formation of hybrid genes by in vivo recombination to introduce two separate mutations into the same gene. The mutants of interest are inserted as head-to-tail tandems in a bacterial plasmid in such a way that the 5'-proximal mutation is located upstream from the mutant with the more distal mutation. Propagation of the plasmid in a rec+ strain of Escherichia coli allows recombination between homologous sequences in the insert. DNA with the size expected for the recombinant plasmid is isolated by agarose gel electrophoresis, cloned in a recA strain, and characterized by restriction endonuclease mapping. Using this procedure, we have transferred the deletion from polyomavirus mutant dl-8 into other mutant genomes lacking the intervening sequences for either middle T or large T.

Use of mouse mammary tumour virus (MMTV)/neu transgenic mice to identify genes collaborating with the c-erbB-2 oncogene in mammary tumour development.

Mouse mammary tumour virus (MMTV)/neu transgenic mice develop clonal or oligoclonal mammary tumours stochastically. The pathology of these tumours is very similar to that of human breast tumours. Moreover, these mouse tumours metastasize in the lungs. We present evidence that this mouse model of human breast tumours can be instrumental in identifying novel genes of two distinct classes (activated oncogenes or tumour suppressor genes) which may collaborate with the c-erbB-2/neu transgenic oncogene.

Genomic scan for genes affecting body composition before and after training in Caucasians from HERITAGE.

An autosomal genomewide search for genes related to body composition and its changes after a 20-wk endurance-exercise training program has been completed in the HERITAGE Family Study. Phenotypes included body mass index (BMI), sum of eight skinfold thicknesses, fat mass (FM), fat-free mass, percent body fat (%Fat), and plasma leptin levels. A maximum of 364 sib-pairs from 99 Caucasian families was studied with the use of 344 markers with single-point and multipoint linkage analyses. Evidence of significant linkage was observed for changes in fat-free mass with the S100A and the insulin-like growth factor I genes (P = 0.0001). Suggestive evidence (2.0 < or = Lod < 3.0; 0.0001 < P < or = 0.001) was also observed for the changes in FM and %Fat at 1q31 and 18q21-q23, in %Fat with the uncoupling protein 2 and 3 genes, and in BMI at 5q14-q21. At baseline, suggestive evidence was observed for BMI at 8q23-q24, 10p15, and 14q11; for FM at 14q11; and for plasma leptin levels with the low-density lipoprotein receptor gene. This is the first genomic scan on genes involved in exercise-training-induced changes in body composition that could provide information on the determinants of weight loss.

Magnetic resonance imaging of thermal coagulation effects in a phantom for calibrating thermal therapy devices.

A material has been developed and tested that permanently records thermal response patterns from heating devices. The material consists of a mixture of polyacrylamide and 18% w/w bovine serum albumin. Thermal denaturation is complete when the local temperature exceeds 70 degrees C, causing a large reduction in the T2 of the material. Three-dimensional distributions of "thermal damage" can be assessed using standard magnetic resonance imaging sequences. The material works well with microwave heating devices and is adaptable for use with ultrasound, radio-frequency, or laser heating devices. Suggested uses include characterizing heating devices prior to treatment and developing new clinical applications for thermal therapies.