Sleep misperception is often observed in insomnia individuals (INS). The extent of misperception varies between different types of INS. The following paper comprised sections which will be aimed at ...studying the sleep EEG and compares it to subjective reports of sleep in individuals suffering from either psychophysiological insomnia or paradoxical insomnia and good sleeper controls. The EEG can be studied without any intervention (thus using the raw data) via either PSG or fine quantitative EEG analyses (power spectral analysis PSA), identifying EEG patterns as in the case of cyclic alternating patterns (CAPs) or by decorticating the EEG while scoring the different transient or phasic events (K-Complexes or sleep spindles). One can also act on the on-going EEG by delivering stimuli so to study their impact on cortical measures as in the case of event-related potential studies (ERPs). From the paucity of studies available using these different techniques, a general conclusion can be reached: sleep misperception is not an easy phenomenon to quantify and its clinical value is not well recognized. Still, while none of the techniques or EEG measures defined in the paper is available and/or recommended to diagnose insomnia, ERPs might be the most indicated technique to study hyperarousal and sleep quality in different types of INS. More research shall also be dedicated to EEG patterns and transient phasic events as these EEG scoring techniques can offer a unique insight of sleep misperception.
La mésestimation du sommeil est souvent observée chez les individus souffrant d’insomnie (INS). Cependant, l’ampleur de cette mésestimation varie entre les types d’INS. Cet article est composé de sections dédiées à l’étude de l’EEG et sa comparaison avec les rapports subjectifs de sommeil d’individus souffrant soit d’insomnie psychophysiologique ou paradoxale et bons dormeurs. L’EEG peut être étudié soit sans intervention (en utilisant les données brutes) comme dans le cas de la polysomnographie ou l’analyse spectrale, soit en identifiant des patrons d’activation comme pour les patrons cycliques alternants (cyclic alternating pattern) ou encore en décortiquant l’EEG en évènements phasiques ou transitoires (complexes-K et fuseaux de sommeil). On peut également agir sur l’EEG en délivrant des sons et en étudiant leur impact sur les ondes de l’EEG comme dans le cas des potentiels évoqués, et surtout ceux cognitifs. Du peu d’études disponibles utilisant ces différentes techniques/mesures, une conclusion générale peut tout de même être tirée : la mésestimation du sommeil n’est pas facilement quantifiable et sa valeur clinique n’est pas adéquatement reconnue. Alors qu’aucune des techniques/mesures définies ici n’est disponible ou recommandée afin de diagnostiquer l’insomnie, la technique utilisant les potentiels évoqués cognitifs semble la plus appropriée ou juste afin de mesurer l’hypervigilance corticale (hyperarousal) et la qualité du sommeil chez les différents types d’individus souffrant d’insomnie. Finalement, plus de recherches devraient être dédiées à l’étude des patrons EEG et des évènements phasiques du sommeil puisque ces techniques apportent une compréhension différemment unique de la mésestimation du sommeil.
The aim of this study was to develop high-throughput, quantitative and highly selective mass spectrometric, targeted immunoassays for clinically important proteins in human plasma or serum.
The ...described method coupled mass spectrometric immunoassay (MSIA), a previously developed technique for immunoenrichment on a monolithic microcolumn activated with an anti-protein antibody and fixed in a pipette tip, to selected reaction monitoring (SRM) detection and accurate quantification of targeted peptides, including clinically relevant sequence or truncated variants.
In this report, we demonstrate the rapid development of MSIA-SRM assays for sixteen different target proteins spanning seven different clinically important areas (including neurological, Alzheimer's, cardiovascular, endocrine function, cancer and other diseases) and ranging in concentration from pg/mL to mg/mL. The reported MSIA-SRM assays demonstrated high sensitivity (within published clinical ranges), precision, robustness and high-throughput as well as specific detection of clinically relevant isoforms for many of the target proteins. Most of the assays were tested with bona-fide clinical samples.
In addition, positive correlations, (R2 0.67–0.87, depending on the target peptide), were demonstrated for MSIA-SRM assay data with clinical analyzer measurements of parathyroid hormone (PTH) and insulin growth factor 1 (IGF1) in clinical sample cohorts.
We have presented a practical and scalable method for rapid development and deployment of MS-based SRM assays for clinically relevant proteins and measured levels of the target analytes in bona fide clinical samples. The method permits the specific quantification of individual protein isoforms and addresses the difficult problem of protein heterogeneity in clinical proteomics applications.
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► Development of high-throughput, SRM assays for 16 clinically important proteins. ► The method coupled mass spectrometric immunoassay (MSIA) to SRM MS. ► Assays demonstrated sensitivity within clinical ranges, precision and robustness. ► Specific detection of isoforms for many of the target proteins was demonstrated. ► SRM and clinical analyzer measurements (PTH, IGF1) were positively correlated.
Chromosomal synteny between the mouse model and humans was used to map a gene for the complex trait of obesity. Analysis of NZB/BINJ x SM/J intercross mice located a quantitative trait locus (QTL) ...for obesity on distal mouse chromosome 2, in a region syntenic with a large region of human chromosome 20, showing linkage to percent body fat (likelihood of the odds LOD score 3.6) and fat mass (LOD score 4.3). The QTL was confirmed in a congenic mouse strain. To test whether the QTL contributes to human obesity, we studied linkage between markers located within a 52-cM region extending from 20p12 to 20q13.3 and measures of obesity in 650 French Canadian subjects from 152 pedigrees participating in the Quebec Family Study. Sib-pair analysis based on a maximum of 258 sib pairs revealed suggestive linkages between the percentage of body fat (P < 0.004), body mass index (P < 0.008), and fasting insulin (P < 0.0005) and a locus extending approximately from ADA (the adenosine deaminase gene) to MC3R (the melanocortin 3 receptor gene). These data provide evidence that a locus on human chromosome 20q contributes to body fat and insulin in a human population, and demonstrate the utility of using interspecies syntenic relationships to find relevant disease loci in humans.
Genetic Variants of FTO Influence Adiposity, Insulin Sensitivity, Leptin Levels, and Resting Metabolic Rate in the Quebec Family Study
Ron Do 1 ,
Swneke D. Bailey 1 ,
Katia Desbiens 2 ,
Alexandre ...Belisle 3 ,
Alexandre Montpetit 3 ,
Claude Bouchard 4 ,
Louis Pérusse 5 6 ,
Marie-Claude Vohl 6 7 and
James C. Engert 1 2 6 8
1 Department of Human Genetics, McGill University, Montréal, Québec, Canada
2 Research Institute of the McGill University Health Centre, Montréal, Québec, Canada
3 McGill University and Genome Québec Innovation Centre, Montréal, Québec, Canada
4 Pennington Biomedical Research Center, Baton Rouge, Louisiana
5 Department of Social and Preventive Medicine, Division of Kinesiology, Laval University, Ste-Foy, Québec, Canada
6 Lipid Research Center, Laval University Hospital Research Center, Ste-Foy, Québec, Canada
7 Department of Food Science and Nutrition, Laval University, Ste-Foy, Québec, Canada
8 Department of Medicine, McGill University, Montréal, Québec, Canada
Address correspondence and reprint requests to Dr. James C. Engert, McGill University, Division of Cardiology, Royal Victoria
Hospital, H7.30, 687 Pine Ave. West, Montréal, Québec, Canada H3A 1A1. E-mail: jamie.engert{at}mcgill.ca
Abstract
OBJECTIVE— A genome-wide association study conducted by the Wellcome Trust Case Control Consortium recently associated single nucleotide
polymorphisms (SNPs) in the FTO (fatso/fat mass and obesity associated) gene with type 2 diabetes. These associations were shown to be mediated by obesity.
Other research groups found similar results in Europeans and Hispanics but not African Americans. The mechanism by which FTO influences obesity and type 2 diabetes is currently unknown. The present study investigated the role of two FTO SNPs (rs17817449 and rs1421085) in adiposity, insulin sensitivity, and body weight regulation, including energy intake and
expenditure.
RESEARCH DESIGN AND METHODS— We genotyped 908 individuals from the Quebec City metropolitan area that participated in the Quebec Family Study, a long-term
study of extensively phenotyped individuals designed to investigate factors involved in adiposity.
RESULTS— We found significant associations for both SNPs with several obesity-related phenotypes. In particular, rs17817449 was associated
with BMI ( P = 0.0014 ), weight ( P = 0.0059), and waist circumference ( P = 0.0021) under an additive model. In addition, this FTO SNP influenced fasting insulin ( P = 0.011), homeostasis model assessment of insulin resistance ( P = 0.038), and an insulin sensitivity index derived from an oral glucose tolerance test ( P = 0.0091). Associations were also found with resting metabolic rate (RMR) ( P = 0.042) and plasma leptin levels ( P = 0.036). Adjustment for BMI abolished the associations with insulin sensitivity, RMR, and plasma leptin levels.
CONCLUSIONS— These results confirm that genetic variation at the FTO locus contributes to the etiology of obesity, insulin resistance, and increased plasma leptin levels.
FFM, fat-free mass
FM, fat mass
HOMA-IR, homeostasis model assessment of insulin resistance
HWE, Hardy-Weinberg equilibrium
ISI, insulin sensitivity index
LD, linkage disequilibrium
MAF, minor allele frequency
MCR, metabolic clearance rate
OGTT, oral glucose tolerance test
QFS, Quebec Family Study
RFLP, restriction fragment–length polymorphism
RMR, resting metabolic rate
SNP, single nucleotide polymorphism
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 3 March 2008. DOI: 10.2337/db07-1267.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/db07-1267 .
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted January 14, 2008.
Received September 6, 2007.
DIABETES
To identify loci associated with abdominal fat and replicate prior findings, we performed genome-wide association (GWA) studies of abdominal fat traits: subcutaneous adipose tissue (SAT); visceral ...adipose tissue (VAT); total adipose tissue (TAT) and visceral to subcutaneous adipose tissue ratio (VSR).
Sex-combined and sex-stratified analyses were performed on each trait with (TRAIT-BMI) or without (TRAIT) adjustment for body mass index (BMI), and cohort-specific results were combined via a fixed effects meta-analysis. A total of 2513 subjects of European descent were available for the discovery phase. For replication, 2171 European Americans and 772 African Americans were available.
A total of 52 single-nucleotide polymorphisms (SNPs) encompassing 7 loci showed suggestive evidence of association (P<1.0 × 10(-6)) with abdominal fat in the sex-combined analyses. The strongest evidence was found on chromosome 7p14.3 between a SNP near BBS9 gene and VAT (rs12374818; P=1.10 × 10(-7)), an association that was replicated (P=0.02). For the BMI-adjusted trait, the strongest evidence of association was found between a SNP near CYCSP30 and VAT-BMI (rs10506943; P=2.42 × 10(-7)). Our sex-specific analyses identified one genome-wide significant (P<5.0 × 10(-8)) locus for SAT in women with 11 SNPs encompassing the MLLT10, DNAJC1 and EBLN1 genes on chromosome 10p12.31 (P=3.97 × 10(-8) to 1.13 × 10(-8)). The THNSL2 gene previously associated with VAT in women was also replicated (P=0.006). The six gene/loci showing the strongest evidence of association with VAT or VAT-BMI were interrogated for their functional links with obesity and inflammation using the Biograph knowledge-mining software. Genes showing the closest functional links with obesity and inflammation were ADCY8 and KCNK9, respectively.
Our results provide evidence for new loci influencing abdominal visceral (BBS9, ADCY8, KCNK9) and subcutaneous (MLLT10/DNAJC1/EBLN1) fat, and confirmed a locus (THNSL2) previously reported to be associated with abdominal fat in women.
Physical aggression in children is a major public health problem. Not only is childhood physical aggression a precursor of the physical and mental health problems that will be visited on victims, but ...also aggressive children themselves are at higher risk of alcohol and drug abuse, accidents, violent crimes, depression, suicide attempts, spouse abuse, and neglectful and abusive parenting. Furthermore, violence commonly results in serious injuries to the perpetrators themselves. Although it is unusual for young children to harm seriously the targets of their physical aggression, studies of physical aggression during infancy indicate that by 17 months of age, the large majority of children are physically aggressive toward siblings, peers, and adults. This study aimed, first, to identify the trajectories of physical aggression during early childhood and, second, to identify antecedents of high levels of physical aggression early in life. Such antecedents could help to understand better the developmental origins of violence later in life and to identify targets for preventive interventions.
A random population sample of 572 families with a 5-month-old newborn was recruited. Assessments of physical aggression frequency were obtained from mothers at 17, 30, and 42 months after birth. Using a semiparametric, mixture model, distinct clusters of physical aggression trajectories were identified. Multivariate logit regression analysis was then used to identify which family and child characteristics, before 5 months of age, predict individuals on a high-level physical aggression trajectory from 17 to 42 months after birth.
Three trajectories of physical aggression were identified. The first was composed of children who displayed little or no physical aggression. These individuals were estimated to account for approximately 28% of the sample. The largest group, estimated at approximately 58% of the sample, followed a rising trajectory of modest aggression. Finally, a group, estimated to comprise approximately 14% of the sample, followed a rising trajectory of high physical aggression. Best predictors before or at birth of the high physical aggression trajectory group, controlling for the levels of the other risk factors, were having young siblings (odds ratio OR: 4.00; confidence interval CI: 2.2-7.4), mothers with high levels of antisocial behavior before the end of high school (OR: 3.1; CI: 1.1-8.6), mothers who started having children early (OR: 3.1; CI: 1.4-6.8), families with low income (OR: 2.6; CI: 1.3-5.2), and mothers who smoked during pregnancy (OR: 2.2; CI: 1.1-4.1). Best predictors at 5 months of age were mothers' coercive parenting behavior (OR: 2.3; CI: 1.1-4.7) and family dysfunction (OR: 2.2; CI: 1.2-4.1). The OR for a high-aggression trajectory was 10.9 for children whose mother reported both high levels of antisocial behavior and early childbearing.
Most children have initiated the use of physical aggression during infancy, and most will learn to use alternatives in the following years before they enter primary school. Humans seem to learn to regulate the use of physical aggression during the preschool years. Those who do not, seem to be at highest risk of serious violent behavior during adolescence and adulthood. Results from the present study indicate that children who are at highest risk of not learning to regulate physical aggression in early childhood have mothers with a history of antisocial behavior during their school years, mothers who start childbearing early and who smoke during pregnancy, and parents who have low income and have serious problems living together. All of these variables are relatively easy to measure during pregnancy. Preventive interventions should target families with high-risk profiles on these variables. Experiments with such programs have shown long-term impacts on child abuse and child antisocial behavior. However, these impacts were not observed in families with physical violence. The problem may be that the prevention programs that were provided did not specifically target the parents' control over their physical aggression and their skills in teaching their infant not to be physically aggressive. Most intervention programs to prevent youth physical aggression have targeted school-age children. If children normally learn not to be physically aggressive during the preschool years, then one would expect that interventions that target infants who are at high risk of chronic physical aggression would have more of an impact than interventions 5 to 10 years later, when physical aggression has become a way of life.
To examine the genetic and environmental influences on variances in weight, height, and BMI, from birth through 19 years of age, in boys and girls from three continents.
Cross-sectional twin study. ...Data obtained from a total of 23 twin birth-cohorts from four countries: Canada, Sweden, Denmark, and Australia. Participants were Monozygotic (MZ) and dizygotic (DZ) (same- and opposite-sex) twin pairs with data available for both height and weight at a given age, from birth through 19 years of age. Approximately 24,036 children were included in the analyses.
Heritability for body weight, height, and BMI was low at birth (between 6.4 and 8.7% for boys, and between 4.8 and 7.9% for girls) but increased over time, accounting for close to half or more of the variance in body weight and BMI after 5 months of age in both sexes. Common environmental influences on all body measures were high at birth (between 74.1-85.9% in all measures for boys, and between 74.2 and 87.3% in all measures for girls) and markedly reduced over time. For body height, the effect of the common environment remained significant for a longer period during early childhood (up through 12 years of age). Sex-limitation of genetic and shared environmental effects was observed.
Genetics appear to play an increasingly important role in explaining the variation in weight, height, and BMI from early childhood to late adolescence, particularly in boys. Common environmental factors exert their strongest and most independent influence specifically in pre-adolescent years and more significantly in girls. These findings emphasize the need to target family and social environmental interventions in early childhood years, especially for females. As gene-environment correlation and interaction is likely, it is also necessary to identify the genetic variants that may predispose individuals to obesity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Data on the relationship between protein intake and the risk of type 2 diabetes are conflicting.
We studied prospective associations between the intake of total, plant-based, and animal protein and ...the risk of pre-diabetes and diabetes in 4 population-based studies included in the PREVIEW project.
Analyses were conducted with the use of data from 3 European cohorts and 1 Canadian cohort, including 78,851 participants. Protein intake was assessed through the use of harmonized data from food-frequency questionnaires or 3-d dietary records. Cohort-specific incidence ratios (IRs) were estimated for pre-diabetes and diabetes, adjusting for general characteristics, lifestyle and dietary factors, disease history, and body mass index (BMI) and waist circumference; results were pooled based on a random-effects meta-analysis.
Higher total protein intake (g · kg–1 · d–1) was associated with lower incidences of pre-diabetes and diabetes (pooled IRs: 0.84; 95% CI: 0.82, 0.87 and 0.49; 95% CI: 0.28, 0.83, respectively); plant-based protein intake was the main determinant (pooled IRs: 0.83; 95% CI: 0.81, 0.86 and 0.53; 95% CI: 0.36, 0.76, respectively). Substituting 2 energy percentage (E%) protein at the expense of carbohydrates revealed increased risks of pre-diabetes and diabetes (pooled IRs: 1.04; 95% CI: 1.01, 1.07 and 1.09; 95% CI: 1.01, 1.18, respectively). Except for the associations between intakes of total protein and plant-based protein (g · kg–1 · d–1) and diabetes, all other associations became nonsignificant after adjustment for BMI and waist circumference.
Higher protein intake (g · kg–1 · d–1) was associated with a lower risk of pre-diabetes and diabetes. Associations were substantially attenuated after adjustments for BMI and waist circumference, which demonstrates a crucial role for adiposity and may account for previous conflicting findings. This study was registered at ISRCTN as ISRCTN31174892.
The present study is an extension of previous work on the dreams of pregnant women, with a large sample from pregnancy and postpartum. In total, 143 pregnant women completed dream diaries during 3 ...distinct periods. Also, 125 nonpregnant women completed a dream diary on 1 occasion. Pregnancy- and motherhood-related oneiric characteristics, as well as negative versus positive dream elements, were coded by 2 independent judges. Results revealed that pregnant women experienced more direct in-dream representations of pregnancy and motherhood than the comparison group. However, no differences in oneiric emotional content were observed between the 2 groups. Results support the continuity hypothesis with respect to thematic representations of pregnancy but are inconclusive regarding emotional content.
The objectives of the study were to examine EEG activities using power spectral analysis (PSA) of good sleepers (GS), psychophysiological (PsyI) and paradoxical (ParI) insomnia sufferers on two ...consecutive nights. Participants completed three nights of PSG recordings in a sleep laboratory following a clinical evaluation. Participants were 26 PsyI, 20 ParI and 21 GS (mean age=40years, SD=9.4). All sleep cycles of Nights 2 and 3 were retained for PSA. The absolute and relative activity in frequency bands (0.00 to 125.00Hz) were computed at multiple frontal, central and parietal sites in REM and NREM sleep. Mixed model ANOVAs were performed with absolute and relative PSA data to assess differences between groups and nights. Over the course of the two nights, more absolute delta activity at F3, C3, and P3 was observed in ParI compared with PsyI suggesting deactivation of the left hemisphere in ParI and/or hyperactivation in PsyI. Further analysis on absolute PSA data revealed that differences between groups relate mostly to NREM. In REM, lower relative activity in slower frequency bands was found in ParI in comparison with GS and less relative theta activity was found in PsyI compared with GS implying higher activation in insomnia. In addition, between nights variability has been found in absolute powers of faster frequency bands (beta to omega). Signs of decreased cortical activity in absolute PSA in NREM combined with increased relative cortical activation in REM were found in ParI which might contribute to the misperception of sleep in ParI.
•Controls' and insomniacs' sleep microstructure were compared at multiple sites.•More absolute delta activity was observed in paradoxical insomniacs in NREM.•Lower relative activity in slower bands was found in paradoxical insomniacs in REM.•In general, higher activation in insomnia was observed compared with good sleepers.•Between nights variability was found in absolute beta to omega activity.
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