Do childhood and adult socioeconomic circumstances influence health and physical function in middle-age?

This study examines the joint and separate contribution of social class in early and adult life to differences in health and physical function in middle-aged men. We use data from the Metropolit project which includes men born in 1953 in Copenhagen and a study of middle-aged Danish twins (MADT). In total 6292 Metropolit participants in a follow-up survey on health in 2004 were included in the study together with 2198 male twins of which 1294 were part of a male twin pair (N = 647 pairs). Logistic regression was used to investigate the association between social class in early and adult life, respectively and health in midlife, measured as limitations in running 100 m, poor dental status, poor self-rated health, and fatigue. In both datasets, men with low childhood or adult social class had a higher risk of being unable to run 100 m, having poor dental status, having poor self-rated health and fatigue than men from the highest social classes. When childhood and adult social class were mutually adjusted, the estimates for both measures were attenuated. Adjustment for living without a partner, body mass index (BMI) and smoking in midlife, which were also related to the four outcomes, had marginal effects on the estimates for childhood social class, but attenuated the effect of adult social class somewhat. Among male twin pairs discordant on adult social class, the twin in the lowest class seemed to be unable to run 100 m, rate own health poorer and being fatigued more often than the high class co-twin, while there seemed to be no twin pair difference in dental status. This suggests that the associations of adult social class with functional limitations, poor self-rated health and fatigue may partly be due to causal effects related to adult social class exposures, while social class differences in dental status might be consistent with an effect of factors mainly operating early in life.     

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. We analyzed 108 SNPs and one insertion in 29 genes involved in folate/one‐carbon metabolism and 68 SNPs from 16 genes involved in vitamin A metabolism. Using the Triad Multi‐Marker (TRIMM) approach we performed SNP, gene, chromosomal region, and pathway‐wide association tests of child or maternal genetic effects for both CL/P and CPO. We stratified these analyses on maternal intake of folic acid or vitamin A during the periconceptional period. As expected with this high number of statistical tests, there were many associations with P‐values<0.05; although there were fewer than predicted by chance alone. The strongest association in our data (between fetal FOLH1 and CPO, P=0.0008) is not in agreement with epidemiologic evidence that folic acid reduces the risk of CL/P in these data, not CPO. Despite strong evidence for genetic causes of oral facial clefts and the protective effects of maternal vitamins, we found no convincing indication that polymorphisms in these vitamin metabolism genes play an etiologic role. Genet. Epidemiol. 2009. © 2008 Wiley Liss, Inc.     

The sumLINK statistic for genetic linkage analysis in the presence of heterogeneity

We present the “sumLINK” statistic—the sum of multipoint LOD scores for the subset of pedigrees with nominally significant linkage evidence at a given locus—as an alternative to common methods to identify susceptibility loci in the presence of heterogeneity. We also suggest the “sumLOD” statistic (the sum of positive multipoint LOD scores) as a companion to the sumLINK. sumLINK analysis identifies genetic regions of extreme consistency across pedigrees without regard to negative evidence from unlinked or uninformative pedigrees. Significance is determined by an innovative permutation procedure based on genome shuffling that randomizes linkage information across pedigrees. This procedure for generating the empirical null distribution may be useful for other linkage‐based statistics as well. Using 500 genome‐wide analyses of simulated null data, we show that the genome shuffling procedure results in the correct type 1 error rates for both the sumLINK and sumLOD. The power of the statistics was tested using 100 sets of simulated genome‐wide data from the alternative hypothesis from GAW13. Finally, we illustrate the statistics in an analysis of 190 aggressive prostate cancer pedigrees from the International Consortium for Prostate Cancer Genetics, where we identified a new susceptibility locus. We propose that the sumLINK and sumLOD are ideal for collaborative projects and meta‐analyses, as they do not require any sharing of identifiable data between contributing institutions. Further, loci identified with the sumLINK have good potential for gene localization via statistical recombinant mapping, as, by definition, several linked pedigrees contribute to each peak. Genet. Epidemiol. 33:628–636, 2009. © 2009 Wiley‐Liss, Inc.     

Effects of temporal context and temporal expectancy on neural activity in inferior temporal cortex

Timing is critical. The same event can mean different things at different times and some events are more likely to occur at one time than another. We used a cued visual classification task to evaluate how changes in temporal context affect neural responses in inferior temporal cortex, an extrastriate visual area known to be involved in object processing. On each trial a first image cued a temporal delay before a second target image appeared. The animal's task was to classify the second image by pressing one of two buttons previously associated with that target. All images were used as both cues and targets. Whether an image cued a delay time or signaled a button press depended entirely upon whether it was the first or second picture in a trial. This paradigm allowed us to compare inferior temporal cortex neural activity to the same image subdivided by temporal context and expectation. Neuronal spiking was more robust and visually evoked local field potentials (LFP's) larger for target presentations than for cue presentations. On invalidly cued trials, when targets appeared unexpectedly early, the magnitude of the evoked LFP was reduced and delayed and neuronal spiking was attenuated. Spike field coherence increased in the beta-gamma frequency range for expected targets. In conclusion, different neural responses in higher order ventral visual cortex may occur for the same visual image based on manipulations of temporal attention.     

Transient intraneuronal Aβ rather than extracellular plaque pathology correlates with neuron loss in the frontal cortex of APP/PS1KI mice

The accumulation of beta-amyloid (Aβ) plaques and neurofibrillary tangles consisting of hyperphosphorylated tau protein are pathological features of Alzheimer’s disease (AD) commonly modeled in mice using known human familial mutations; however, the loss of neurons also found to occur in AD is rarely observed in such models. The mechanism of neuron degeneration remains unclear but is of great interest as it is very likely an important factor for the onset of adverse memory deficits occurring in individuals with AD. The role of Aβ in the neuronal degeneration is a matter of controversial debates. In the present study we investigated the impact of extracellular plaque Aβ versus intraneuronal Aβ on neuronal cell death. The thalamus and the frontal cortex of the APP/PS1KI mouse model were chosen for stereological quantification representing regions with plaques only (thalamus) or plaques as well as intraneuronal Aβ (frontal cortex). A loss of neurons was found in the frontal cortex at the age of 6 months coinciding with the decrease of intraneuronal immunoreactivity, suggesting that the neurons with early intraneuronal Aβ accumulation were lost. Strikingly, no neuron loss was observed in the thalamus despite the development of abundant plaque pathology with levels comparable to the frontal cortex. This study suggests that plaques have no effect on neuron death whereas accumulation of intraneuronal Aβ may be an early transient pathological event leading to neuron loss in AD. O. Wirths and T. A. Bayer have equally contributed to this work.     

Gender differences in the endorsement of symptoms for depression and anxiety: are gender-biased items responsible?

Gender-biased items are one explanation for the gender difference in reports of depression and anxiety symptoms. This hypothesis was explored using responses from the Goldberg Anxiety and Depression scales. Responses were drawn from 2 waves of a community-based survey with participants in 3 age cohorts: 20 to 25, 40 to 44, and 60 to 64 at wave 1. The results showed that a 2-factor model fitted the scales well. Multiple group analyses showed that that for all 3 age groups and both time points the fit indices changed minimally between a model that constrained parameters to be equal across gender and a model that permitted variation. These findings indicate that gender differences in the endorsement of items from the Goldberg scales are not because of gender-biased items. This study points to alternate biopsychosocial explanations and highlights the importance of choosing appropriate methods of analysis when assessing item bias.     

Amiodarone protects diabetics and non-diabetics undergoing coronary artery bypass grafting equally

OBJECTIVE: To evaluate amiodarone prophylaxis in diabetics and non-diabetics. Further to clarify whether the risk of developing atrial fibrillation is higher for diabetics than non-diabetic patients, and to evaluate whether the diabetic status has any influence on the length of in-hospital stay. DESIGN: Subgroup analysis within a randomized, controlled, double-blinded trial. RESULTS: At 30 days of follow-up atrial fibrillation was equally frequent among diabetics (22%) and non-diabetics (17%) (p =0.41). The length of in-hospital stay for diabetics was prolonged with 25% (9%; 45%). The prophylactic amiodarone was found equally efficient in diabetics and non-diabetics, as the relative risk ratios were 1.2 (0.4-5.4) and 2.0 (0.3-12.5), respectively. CONCLUSIONS: Diabetics and non-diabetics had the same effect of the amiodarone prophylaxis regime. Atrial fibrillation developed equally among diabetics and non-diabetics, but the length of stay was prolonged for diabetics.