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Background: Psychological distress (PD) and depressive symptoms are commonly observed during menopausal transition. Studies suggest that omega-3 (n-3) fatty acids may help alleviate depression., Objective: The objective was to compare enriched ethyl-eicosapentaenoic acid (E-EPA) supplementation with placebo for the treatment of PD and depressive symptoms in middle-aged women., Design: Women with moderate-to-severe PD (n = 120) were randomly assigned to receive 1.05 g E-EPA/d plus 0.15 g ethyl-docosahexaenoic acid/d (n = 59) or placebo (n = 61) for 8 wk. The main outcomes were 8-wk changes in PD scores [Psychological General Well-Being Schedule (PGWB)] and depressive scales [20-item Hopkins Symptom Checklist Depression Scale (HSCL-D-20) and the 21-item Hamilton Depression Rating Scale (HAM-D-21)]., Results: At baseline, women with PD were mildly to moderately depressed, and 24% met the major depressive episode (MDE) criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. After 8 wk, outcomes improved in both groups, but no significant differences were noted between them. Stratification analyses for MDE diagnosis at baseline indicated that differences in adjusted 8-wk changes between the E-EPA group without MDE (n = 46) and the placebo group (n = 45) were 8.0 (95% CI: 0.6, 15.3; P = 0.034) for the PGWB, -0.2 (95% CI: -0.01, -0.4; P = 0.040) for the HSCL-D-20, and -2.7 (95% CI: -0.3, -5.1; P = 0.030) for the HAM-D-21. Differences in adjusted 8-wk changes between the E-EPA group with MDE (n = 13) and the placebo group (n = 16) were not significant., Conclusions: To our knowledge, this is the first trial of n-3 supplementation in the treatment of PD and depressive symptoms in middle-aged women. In women with PD without MDE at baseline, the 8-wk changes in PD and depressive scales improved significantly more with E-EPA than with placebo. This trial was registered at http://www.controlled-trials.com as ISRCTN69617477.

Objective: We sought to evaluate the association between inherited thrombophilia and preeclampsia., Study Design: From a multicenter cohort of 5337 pregnant women, we prospectively identified 113 women who developed preeclampsia and selected 443 control subjects who did not have preeclampsia or nonproteinuric gestational hypertension. Blood samples were tested for DNA polymorphisms affecting thrombophilia (factor V Leiden mutation, prothrombin G20210A mutation, methylenetetrahydrofolate reductase C677T polymorphism), homocysteine, and folate levels, and placentae underwent pathological evaluation., Results: Thrombophilia was present in 14% of patients and 21% of control subjects (adjusted logistic regression odds ratio, 0.6; 95% confidence interval, 0.3-1.3). Placental underperfusion was present in 63% of patients vs 46% of control subjects (P < .001) and was more frequent in women with folate levels in the lowest quartile (P = .04), but was not associated with thrombophilia., Conclusion: We did not find evidence to support an association between inherited thrombophilia and increased risk of preeclampsia. Placental underperfusion is associated with preeclampsia, but this does not appear to be consequent to thrombophilia.

We describe an autosomal-dominant locus for Restless Legs Syndrome (RLS) in a French-Canadian (FC) pedigree. Genome-wide microsatellite scan and linkage analysis were used in this study. The locus maps to chromosome 16p12.1 and spans 1.18 Mega bases. The maximum multipoint LOD scores are of 3.5 over the total of 10 markers. Evidence for the same locus was also found in a smaller FC pedigree sime095. The analysis of the sequence of 8 annotated genes within the region did not reveal any pathogenic mutations. Copy number variation and karyotype analyses did not reveal any chromosomal abnormality in the region. Further analyses of the region are necessary to find the genetic cause of RLS in this family.

Background: In families segregating a monogenic genetic disorder with a single disease gene introduction, patients share a mutation-carrying chromosomal interval with identity-by-descent (IBD). Such a shared chromosomal interval or haplotype, surrounding the actual pathogenic mutation, is typically detected and defined by multipoint linkage and phased haplotype analysis using microsatellite or SNP genotype data. High-density SNP genotype data presents a computational challenge for conventional genetic analyses. A novel non-parametric method termed Homozygosity Haplotype (HH) was recently proposed for the genome-wide search of the autosomal segments shared among patients using high density SNP genotype data., Methodology/principal Findings: The applicability and the effectiveness of HH in identifying the potential linkage of disease causative gene with high-density SNP genotype data were studied with a series of monogenic disorders ascertained in eastern Canadian populations. The HH approach was validated using the genotypes of patients from a family affected with a rare autosomal dominant disease Schnyder crystalline corneal dystrophy. HH accurately detected the approximately 1 Mb genomic interval encompassing the causative gene UBIAD1 using the genotypes of only four affected subjects. The successful application of HH to identify the potential linkage for a family with pericentral retinal disorder indicates that HH can be applied to perform family-based association analysis by treating affected and unaffected family members as cases and controls respectively. A new strategy for the genome-wide screening of known causative genes or loci with HH was proposed, as shown the applications to a myoclonus dystonia and a renal failure cohort., Conclusions/significance: Our study of the HH approach demonstrates that HH is very efficient and effective in identifying potential disease linked region. HH has the potential to be used as an efficient alternative approach to sequencing or microsatellite-based fine mapping for screening the known causative genes in genetic disease study.

Objective: Due to its high content of lignans, alpha-linolenic acid and fiber, flaxseed may reduce cardiovascular disease risk in humans. The present study evaluated the effect of flaxseed on markers of cardiovascular disease risk in healthy menopausal women., Methods: One hundred ninety-nine women were randomly assigned to consume 40 g daily of flaxseed or wheat germ placebo for 12 mo. Fatty acids, apolipoproteins A-1 and B, lipoprotein(a), low-density lipoprotein particle size, fibrinogen, C-reactive protein, insulin, and glucose were measured at baseline and at 12 mo., Results: In total 179 women were available for the intention-to-treat analysis. Flaxseed increased plasma alpha-linolenic (P < 0.0001), docosapentaenoic (P = 0.001), and total omega-3 fatty (P = 0.0004) acids. Differences between flaxseed and wheat germ were observed for apolipoprotein A-1 (-0.10 +/- 0.26 g/L, P = 0.011) and apolipoprotein B (-0.05 +/- 0.16 g/L, P = 0.047). From baseline, flaxseed raised apolipoproteins A-1 and B by 4.4% (P = 0.006) and 3% (P = 0.054), whereas wheat germ increased these apolipoproteins by 11.6% (P < 0.0001) and 7% (P = 0.0001), respectively. Both treatments increased lipoprotein(a) (P < 0.0001) and decreased low-density lipoprotein peak particle size (P < 0.0001)., Conclusion: In this large, long-term, placebo-controlled trial in healthy menopausal women, flaxseed increased some omega-3 fatty acids in plasma and had a limited effect on apolipoprotein metabolism.

The objective of the present study was to investigate the effect of three modified milk fats with different melting profiles on fasting and postprandial lipid responses and on fecal fat content in guinea pigs. We hypothesized that the consumption of modified milk fat with a high m.p. results in reduced fasting and postprandial lipid responses compared with that of modified milk fat fractions with lower m.p. To test this hypothesis, male Hartley guinea pigs were fed isoenergetic diets containing 110 g of fat/kg, either from one of the three modified milk fats with high (HMF), medium (MMF), or low melting profiles (LMF), or from one of the two reference fats as whole milk fat (MF) or a fat blend similar to that of nonhydrogenated soft margarine (MA) for 28 d. Food intake (P < 0.05) and body weight gain (P < 0.05) were reduced in the animals fed the HMF diet compared with the other groups. In the fasting state, plasma LDL cholesterol was highest in animals fed the LMF diet, intermediary in those fed the MMF and MF diets, and lowest in those fed the HMF and MA diets (P< 0.05). Postprandially, the areas under the 0- to 3-h curves for the changes in plasma TG were lower in the HMF group than in the MA- and LMF-fed guinea pigs (P< 0.05). The fecal fat content was higher (P< 0.05) in the HMF group compared to the other milk fat groups. The present results suggest that modified milk fats can impact food intake, body weight gain, fasting cholesterolemia, and postprandial triglyceridemia, and these changes may be attributed to an altered fat absorption.

Dystocia, or slow labor, is the leading cause of first-time cesarean sections. Current diagnostic guidelines for dystocia are vague, and there is no clear postoperative confirmatory evidence to assess the correctness of this diagnosis. For several decades, various professional organizations have indicated that cesarean rates could be lowered safely and have recommended levels that are far below national averages. The three major factors, of roughly equal importance, associated with cesarean for slow labor are the baby's weight, the mother's height, and the threshold at which the physician believes it is reasonable to intervene. The last is the only modifiable factor, and quality programs are a major part of changing medical behavior. By using two study designs, the effect of a mathematical method for evaluating labor progress on the rate of cesarean section was measured. In the prospective randomized clinical trial, the relative risk of cesarean in the experimental group was unchanged at 1.04. In the pretest-posttest analysis, the rates fell from 19.54% to 17.04% at 6 months and 16.62% at 12 months.

In the present study, we tested the hypothesis that fish protein may represent a key constituent of fish with glucoregulatory activity. Three groups of rats were fed a high-fat diet in which the protein source was casein, fish (cod) protein, or soy protein; these groups were compared with a group of chow-fed controls. High-fat feeding led to severe whole body and skeletal muscle insulin resistance in casein- or soy protein-fed rats, as assessed by the euglycemic clamp technique coupled with measurements of 2-deoxy-D-[(3)H]glucose uptake rates by individual tissues. However, feeding cod protein fully prevented the development of insulin resistance in high fat-fed rats. These animals exhibited higher rates of insulin-mediated muscle glucose disposal that were comparable to those of chow-fed rats. The beneficial effects of cod protein occurred without any reductions in body weight gain, adipose tissue accretion, or expression of tumor necrosis factor-alpha in fat and muscle. Moreover, L6 myocytes exposed to cod protein-derived amino acids showed greater rates of insulin-stimulated glucose uptake compared with cells incubated with casein- or soy protein-derived amino acids. These data demonstrate that feeding cod protein prevents obesity-induced muscle insulin resistance in high fat-fed obese rats at least in part through a direct action of amino acids on insulin-stimulated glucose uptake in skeletal muscle cells.

Preterm birth is the leading cause of infant mortality in industrialised societies. Its incidence is greatly increased among the socially disadvantaged, but the reasons for this excess are unclear and have been relatively unexplored. We hypothesise two distinct sets of causal pathways and mechanisms that may explain social disparities in preterm birth. The first set involves chronic and acute psychosocial stressors, psychological distress caused by those stressors, increased secretion of placental corticotropin releasing hormone (CRH), changes in sexual behaviours or enhanced susceptibility to bacterial vaginosis and chorioamnionitis, cigarette smoking or cocaine use, and decidual vasculopathy. The second hypothesised pathway is a gene-environment interaction based on a highly prevalent mutation in the gene for methylenetetrahydrofolate reductase (MTHFR), combined with low folate intake from the diet and from prenatal vitamin supplements, consequent hyperhomocysteinemia, and decidual vasculopathy. We propose to test these hypothesised pathways and mechanisms in a nested case-control study within a prospectively recruited and followed cohort of pregnant women with singleton pregnancies who deliver at one of four Montreal hospitals that serve an ethnically and socio-economically diverse population. Following recruitment during the late first or early second trimester, participating women are seen at 24-26 weeks, when a research nurse obtains a detailed medical and obstetric history; administers several scales to assess chronic and acute stressors and psychological function; obtains blood samples for CRH, red blood cell and plasma folate, homocysteine, and DNA for the MTHFR mutation; and performs a digital and speculum examination to measure cervical length and vaginal pH and to obtain swabs for bacterial vaginosis and fetal fibronectin. After delivery, each case (delivery at < 37 completed weeks following spontaneous onset of labour or prelabour rupture of membranes) and two controls are selected for placental pathological examination, hair analysis of cotinine, cocaine, and benzoylecgonine, and analysis of stored blood and vaginal specimens. Statistical analysis will be based on multiple logistic regression and structural equation modelling, with sequential construction of models of potential aetiological determinants and covariates to test the hypothesised causal pathways and mechanisms. The research we propose should improve understanding of the factors and processes that mediate social disparities in preterm birth. This improved understanding should help not only in developing strategies to reduce the disparities but also in suggesting preventive interventions applicable across the entire socio-economic spectrum.