The association of maternal factors with delayed implantation and the initial rise of urinary human chorionic gonadotrophin.

BACKGROUND Late implantation and the pattern of early rise in hCG have been associated with early pregnancy loss. We explored factors that might be predictive of these markers of poor embryonic health in spontaneously conceived pregnancies. METHODS Participants in the North Carolina Early Pregnancy Study collected daily first-morning urine specimens while attempting to conceive.

An exploratory study on the CHRNA3-CHRNA5-CHRNB4 cluster, smoking, and Parkinson's disease.

Background: Smokers have a lower risk of Parkinson's disease (PD). Recent genome-wide association studies (GWAS) have consistently linked several single nucleotide polymorphisms (SNPs) in the CHRNA3-CHRNA5-CHRNB4 cluster on chromosome 15.q25 to smoking behaviors and nicotine dependence.

Advances in systolic heart failure.

Heart failure due to systolic dysfunction has enormous global impact. Medical management based on an understanding of the pathophysiology of the disease as well as its neurohormonal mechanisms has greatly advanced over the past 25 years. Below is a review of recent and emerging data on epidemiology and diagnosis of heart failure due to systolic dysfunction and the current and future management techniques to ameliorate this disease.

Maternal genes and facial clefts in offspring: a comprehensive search for genetic associations in two population-based cleft studies from Scandinavia.

Background: Fetal conditions can in principle be affected by the mother's genotype working through the prenatal environment.

Methodology/principal Findings: Genotypes for 1536 SNPs in 357 cleft candidate genes were available from a previous analysis in which we focused on fetal gene effects. After data-cleaning, genotypes for 1315 SNPs in 334 autosomal genes were available for the current analysis of maternal gene effects.

Effects of early pregnancy loss on hormone levels in the subsequent menstrual cycle.

Previous studies of hormone patterns after clinical miscarriage suggest reduced pituitary function. Hormonal effects of very early pregnancy loss (before 6 weeks gestation) have not been described. We used within-woman differences between menstrual cycles in urinary hormone measurements from women in the North Carolina Early Pregnancy Study to describe hormonal changes after very early pregnancy loss (n = 28 early losses; 80 non-conception comparison cycles).

The changing paradigm of stress echocardiography: risk stratification, prognosis, and future directions.

The use of stress echocardiography has undergone considerable evolution in the past 3 decades. Although stress echocardiography was first introduced as a noninvasive diagnostic tool for determining the presence or absence of coronary artery disease (CAD), it later served a prognostic role as well. The importance of stress echocardiography in risk stratification and prognosis is substantially undervalued by clinicians.

Testing haplotype-environment interactions using case-parent triads.

Objective: Joint analysis of multiple SNP markers can be informative, but studying joint effects of haplotypes and environmental exposures is challenging. Population structure can involve both genes and exposures and a case-control study is susceptible to bias from either source of stratification. We propose a procedure that uses case-parent triad data and, though not fully robust, resists bias from population structure.

The genetics of preterm birth: using what we know to design better association studies.

Women delivering preterm are at greatly increased risk of another preterm birth in subsequent pregnancies, reflecting effects of the environment, genetics, or both. Recent literature tells an increasingly coherent story about genetic susceptibility. Women who change partners after delivering preterm retain their elevated risk, whereas fathers who change partners do not.

The molecular basis of the effect of temperature on enzyme activity.

Experimental data show that the effect of temperature on enzymes cannot be adequately explained in terms of a two-state model based on increases in activity and denaturation. The Equilibrium Model provides a quantitative explanation of enzyme thermal behaviour under reaction conditions by introducing an inactive (but not denatured) intermediate in rapid equilibrium with the active form. The temperature midpoint (Teq) of the rapid equilibration between the two forms is related to the growth temperature of the organism, and the enthalpy of the equilibrium (DeltaHeq) to its ability to function over various temperature ranges.

Pesticide exposure and hypertensive disorders during pregnancy.

Background: Hypertensive disorders of pregnancy, including pregnancy-induced hypertension (PIH) and preeclampsia (PE), complicate 2-8% of pregnancies. Few studies have examined environmental risk factors in relation to these conditions.

Objectives: Our goal was to examine whether pesticide exposure during pregnancy was associated with hypertensive disorders of pregnancy.

Ultraviolet radiation intensity predicts the relative distribution of dermatomyositis and anti-Mi-2 autoantibodies in women.

Objective: Because studies suggest that ultraviolet (UV) radiation modulates the myositis phenotype and Mi-2 autoantigen expression, we conducted a retrospective investigation to determine whether UV radiation may influence the relative prevalence of dermatomyositis and anti-Mi-2 autoantibodies in the US.

Methods: We assessed the relationship between surface UV radiation intensity in the state of residence at the time of onset with the relative prevalence of dermatomyositis and myositis autoantibodies in 380 patients with myositis from referral centers in the US. Myositis autoantibodies were detected by validated immunoprecipitation assays.

Using cases and parents to study multiplicative gene-by-environment interaction.

With case-parent triads, one can estimate genotype relative risks by measuring the apparent overtransmission of susceptibility genotypes from parents to affected offspring. Results obtained using such designs, properly analyzed, resist both bias due to population structure and bias due to self-selection. Most diseases are not purely genetic, and environmental cofactors can also be important.

Within-person variability in urinary bisphenol A concentrations: measurements from specimens after long-term frozen storage.

Background: Bisphenol A (BPA) is an estrogenic contaminant of food and water associated with adverse developmental effects in laboratory animals. BPA has recently been linked to morbidity in adult humans, but studies of developmental effects in humans are methodologically more difficult. The ability to measure BPA in urine samples after long-term storage could aid in such studies.

Genetic determinants of facial clefting: analysis of 357 candidate genes using two national cleft studies from Scandinavia.

Background: Facial clefts are common birth defects with a strong genetic component. To identify fetal genetic risk factors for clefting, 1536 SNPs in 357 candidate genes were genotyped in two population-based samples from Scandinavia (Norway: 562 case-parent and 592 control-parent triads; Denmark: 235 case-parent triads).

Methodology/principal Findings: We used two complementary statistical methods, TRIMM and HAPLIN, to look for associations across these two national samples.

Using case-parent triads to estimate relative risks associated with a candidate haplotype.

Estimating haplotype relative risks in a family-based study is complicated by phase ambiguity and the many parameters needed to quantify relative risks for all possible diplotypes. This problem becomes manageable if a particular haplotype has been implicated previously as relevant to risk. We fit log-linear models to estimate the risks associated with a candidate haplotype relative to the aggregate of other haplotypes.

Within-person variability in urinary phthalate metabolite concentrations: measurements from specimens after long-term frozen storage.

Laboratory studies show that exposure to phthalates during development can cause adverse effects, especially for males. Studies in humans would be facilitated by collection of urine during pregnancy, long-term storage, and measurement of phthalate metabolites at the time that offspring health is assessed. Our aims were to measure urinary phthalate metabolites after long-term freezer storage, to use those measurements to evaluate within-woman variability over 2- and 4-week intervals, and to determine whether the phases of the menstrual cycle affect metabolite levels.

Oral facial clefts and gene polymorphisms in metabolism of folate/one-carbon and vitamin A: a pathway-wide association study.

An increased risk of facial clefts has been observed among mothers with lower intake of folic acid or vitamin A around conception. We hypothesized that the risk of clefts may be further moderated by genes involved in metabolizing folate or vitamin A. We included 425 case-parent triads in which the child had either cleft lip with or without cleft palate (CL/P) or cleft palate only (CPO), and no other major defects.

Measuring menstrual discomfort: a comparison of interview and diary data.

Background: Menstrual discomfort is common among women of reproductive age and can be debilitating. The accuracy of self-report of menstrual discomfort is unknown.

Methods: At enrollment into the DES Reproductive Health Study in 1990, premenopausal women classified their frequency of any menstrual discomfort as "always," "often," "sometimes," and "never.

A hybrid design: case-parent triads supplemented by control-mother dyads.

Hybrid designs arose from an effort to combine the benefits of family-based and population-based study designs. A recently proposed hybrid approach augments case-parent triads with population-based control-parent triads, genotyping everyone except the control offspring. Including parents of controls substantially improves statistical efficiency for testing and estimating both offspring and maternal genetic relative risk parameters relative to using case-parent triads alone.

Making the most of case-mother/control-mother studies.

The prenatal environment plays an important role in many conditions, particularly those with onset early in life, such as childhood cancers and birth defects. Because both maternal and fetal genotypes can influence risk, investigators sometimes use a case-mother/control-mother design, with mother-offspring pairs as the unit of analysis, to study genetic factors. Risk models should account for both the maternal genotype and the correlated fetal genotype to avoid confounding.

The Spx paralogue MgsR (YqgZ) controls a subregulon within the general stress response of Bacillus subtilis.

The alternative sigma factor sigma(B) of Bacillus subtilis is responsible for the induction of the large general stress regulon comprising approximately 150-200 genes. YqgZ, a member of the sigma(B) regulon, resembles the global regulator Spx of the diamide stress regulon in B. subtilis.

Less is more, except when less is less: Studying joint effects.

Most diseases are complex in that they are caused by the joint action of multiple factors, both genetic and environmental. Over the past few decades, the mathematical convenience of logistic regression has served to enshrine the multiplicative model, to the point where many epidemiologists believe that departure from additivity on a log scale implies that two factors interact in causing disease. Other terminology in epidemiology, where students are told that inequality of relative risks across levels of a second factor should be seen as "effect modification," reinforces an uncritical acceptance of multiplicative joint effect as the biologically meaningful no-interaction null.

Plasminogen alleles influence susceptibility to invasive aspergillosis.

Invasive aspergillosis (IA) is a common and life-threatening infection in immunocompromised individuals. A number of environmental and epidemiologic risk factors for developing IA have been identified. However, genetic factors that affect risk for developing IA have not been clearly identified.