An association of CYP2A6 genotype and smoking topography.

Nicotine is metabolized into biologically inactive cotinine primarily by the cytochrome P450 enzyme CYP2A6. CYP2A6 genetic variations have been phenotypically grouped as slow, intermediate, and normal metabolizers. Slow metabolizers smoke fewer cigarettes daily and weekly, and have lower carbon monoxide (CO) and plasma nicotine levels, suggesting a reduced smoking rate compared with normal metabolizers. CYP2A6 also is involved in the metabolic activation of tobacco-specific procarcinogenic nitrosamines, such as 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). NNK is one of the most abundant and potent procarcinogens in cigarette smoke. The present study investigated the association of CYP2A6 genotype with smoking topography, a quantifiable measure of smoking behavior, in a sample of treatment-seeking smokers prior to treatment. Smoking topography measures indicative of quantity of smoke exposure--number of puffs, mean puff volume, and total puff volume--were the outcome variables. Covariates associated with smoking topography were included in the analyses. Results indicated that CYP2A6 genotype group had a significant effect on mean puff volume and total puff volume, but not number of puffs, such that slow metabolizers exhibited reduced puffing compared with others. Smokers having CYP2A6 variants resulting in low activity metabolize nicotine more slowly, and convert procarcinogen nitrosamines to carcinogens more slowly, than do normal metabolizers. The results from this study also suggest a behavioral mechanism that may account for reduced cancer risk in slow metabolizers.     

Genetic variation in mu-opioid-receptor-interacting proteins and smoking cessation in a nicotine replacement therapy trial.

Extending a previous finding of an association between functional genetic variation in the mu-opioid receptor gene and response to nicotine replacement therapy, we explored the role of genetic variants in two genes encoding mu-opioid-receptor-interacting proteins, namely ARRB2 and HINT1. Participants were 374 smokers treated for nicotine dependence with either transdermal nicotine or nicotine nasal spray for 8 weeks in an open-label randomized trial. In a logistic regression model controlling for OPRM1 genotype, treatment type, and other covariates, we found no significant main effect of ARRB2 genotype on abstinence at either end of treatment or 6-month follow-up. Participants with the HINT1 TT genotype had significantly higher abstinence rates at 6-month follow-up, but this may not be a pharmacogenetic effect, given that the participants were drug free during this time. Haplotype analysis did not reveal any significant associations for either gene. We found an interaction of ARRB2 and OPRM1 genotype on abstinence at 6 months that approached significance; however, interpretation of this finding is limited by the small number of participants with the minor alleles for both genes. Although these data do not provide support for the role of genetic variation in these mu-opioid-receptor-interacting proteins and smoking cessation, further exploration of opioid pathway genes in larger prospective pharmacogenetic trials may be warranted.     

A Comprehensive Assessment of Qualitative and Quantitative Prodromal Parkinsonian Features in Carriers of Gaucher Disease—Identifying Those at the Greatest Risk

Carriers of GBA1 gene variants have a significant risk of developing Parkinson’s disease (PD). A cohort study of GBA carriers between 40–75 years of age was initiated to study the presence of prodromal PD features. Participants underwent non-invasive tests to assess different domains of PD. Ninety-eight unrelated GBA carriers were enrolled (43 males) at a median age (range) of 51 (40–74) years; 71 carried the N370S variant (c.1226A > G) and 25 had a positive family history of PD. The Montreal Cognitive Assessment (MoCA) was the most frequently abnormal (23.7%, 95% CI 15.7–33.4%), followed by the ultrasound hyperechogenicity (22%, 95% CI 14–32%), Unified Parkinson’s Disease Rating Scale part III (UPDRS-III) (17.2%, 95% CI 10.2–26.4%), smell assessment (12.4%, 95% CI 6.6–20.6%) and abnormalities in sleep questionnaires (11%, 95% CI 5.7–19.4%). Significant correlations were found between tests from different domains. To define the risk for PD, we assessed the bottom 10th percentile of each prodromal test, defining this level as “abnormal”. Then we calculated the percentage of “abnormal” tests for each subject; the median (range) was 4.55 (0–43.5%). Twenty-two subjects had more than 15% “abnormal” tests. The limitations of the study included ascertainment bias of individuals with GBA-related PD in relatives, some incomplete data due to technical issues, and a lack of well-characterized normal value ranges in some tests. We plan to enroll additional participants and conduct longitudinal follow-up assessments to build a model for identifying individuals at risk for PD and investigate interventions aiming to delay the onset or perhaps to prevent full-blown PD.     

Psychological aspects of genetic testing: Introduction to the special issue.

Research in molecular genetics has led to the identification of a growing number of disease-predisposing genes. With increasing commercial pressures and public interest in genetic testing, genetic tests are likely to become an integral part of routine medical care. Awareness of genetic risk can facilitate informed medical decision making and, in some cases, can promote risk reduction behaviors that have the potential to reduce morbidity and mortality. Despite these potential medical benefits, there are serious concerns about the psychosocial sequelae of an individual learning that he or she carries an elevated risk for disease. This special issue of Health Psychology is devoted to research that seeks to provide an empirical foundation for the understanding of the psychosocial aspects of genetic testing for disease predisposition. The introduction to the special issue provides a brief overview of patterns of inheritance and genetic testing. This overview is followed by a consideration of the unique features of genetic information that make it different from other types of health threats studied by health psychologists. Finally, this author summarizes the organization of the issue, highlighting key study findings and suggesting future directions for this new field of research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Precordial QT dispersion and inducible ventricular tachycardia

We compared the performance of precordial QT dispersion, late potentials on the signal-averaged electrocardiogram (ECG), and reduced left ventricular ejection fraction for identification of inducible ventricular tachycardia (VT) in 162 patients undergoing electrophysiologic study (EPS). QT(apex) dispersion in 56 patients with inducible VT (72 +/- 55 msec) was greater than that in 106 patients without inducible VT (55 +/- 36 msec, p < 0.01); dispersion was greater in both groups than in 144 normal subjects (33 +/- 19 msec). A QT(apex) dispersion partition of more than 68 msec, the upper ninety-fifth percentile in normal subjects, identified inducible VT with a specificity of 75% and a sensitivity of 45%. Although the performances of late potentials (specificity 82%, sensitivity 59%) and reduced ejection fraction (specificity 86%, sensitivity 54%) were each stronger than QT dispersion alone for identification of inducible VT, abnormal QT(apex) dispersion remained a significant additional predictor of inducible VT in a logistic regression model that included the three variables (specificity 78%, sensitivity 75%).     

What you don't know can hurt you: adverse psychologic effects in members of BRCA1-linked and BRCA2-linked families who decline genetic testing

PURPOSE: To identify members of hereditary breast and ovarian cancer families who are at risk for adverse psychologic effects of genetic testing. PATIENTS AND METHODS: A prospective cohort study with baseline (preeducation) assessments of predictor variables (ie, sociodemographic factors, cancer history, and cancer-related stress symptoms) was performed. The primary outcome variable (presence of depressive symptoms) was assessed at baseline and at 1- and 6-month follow-up evaluations. Participants were 327 adult male and female members of BRCA1- and BRCA2-linked hereditary breast and ovarian cancer families, who were identified as carriers, noncarriers, or decliners of genetic testing. RESULTS: The presence of cancer-related stress symptoms at baseline was strongly predictive of the onset of depressive symptoms in family members who were invited but declined testing. Among persons who reported high baseline levels of stress, depression rates in decliners increased from 26% at baseline to 47% at 1-month follow-up; depression rates in noncarriers decreased and in carriers showed no change (odds ratio [OR] for decliners v noncarriers=8.0; 95% confidence interval [CI], 1.9 to 33.5; P=.0004). These significant differences in depression rates were still evident at the 6-month follow-up evaluation (P=.04). CONCLUSION: In BRCA1/2-linked families, persons with high levels of cancer-related stress who decline genetic testing may be at risk for depression. These family members may benefit from education and counseling, even if they ultimately elect not to be tested, and should be monitored for potential adverse effects.     

Aerobic stability of wheat silages in a subtropical climate

Batches of wheat silage stored under farm conditions in bunker silos at two locations in Israel were exposed to air for up to 3 days in order to study their aerobic stability. Each batch was examined five times at approximately two month intervals during 1983/84 for changes in dry matter, pH, watersoluble carbohydrates, in vitro digestibility, ash, crude protein, ammonianitrogen, glucose, crude fibre, volatile fatty acids, lactic acid, moulds, yeasts and aerobic bacteria. Consistent changes in silage composition after 3 days of aerobic exposure were noticed with an increase in dry matter and in mould counts, and a decrease in acetic acid and in most cases also in lactic acid. Yeasts and bacteria had a tendency to increase during the 3 days of air exposure. Experiments carried out under laboratory conditions with silages kept at 26°C in an atmosphere of 99% RH showed that after 3 days there was only a slight increase in dry matter, a decrease in acetic and lactic acids, watersoluble carbohydrates and ammonia-nitrogen, and an increase in the total number of micro-organisms. Only after 7 days did the deterioration process start.     

Layout simulation for keyboards

The oldest element on any personal computer is the keyboard: its design (the spatial position of the keys in relation to each other) and its layout (the assignment of letters, numerals, and other signs to keys). The are exactly the same as on the first typewriters of over 100 years ago or are they? The layout has been the topic of improvement for more than 70 years but no real change has materialized. We contribute to the efforts of layout reformers in Pollatschek et al. (1986).

In this paper, we introduce a simple simulation tool for evaluating layout, while in an accompanying communication we advise on a cheap and effective way to convert any given layout to any desired one.     

Pauses and Response Latencies: A Chronemic Analysis of Asynchronous CMC

This study examines the chronemics of response latencies in asynchronous computer‐mediated communication (CMC) by analyzing three datasets comprising a total of more than 150,000 responses: email responses created by corporate employees, responses created by university students in course discussion groups, and responses to questions posted in a public, commercial online information market. Mathematical analysis of response latencies reveals a normative pattern common to all three datasets: The response latencies yielded a power‐law distribution, such that most of the responses (at least 70%) were created within the average response latency of the responders, while very few (at most 4%) of the responses were created after a period longer than 10 times the average response latency. These patterns persist across diverse user populations, contexts, technologies, and average response latencies. Moreover, it is shown that the same pattern appears in traditional, spoken communication and in other forms of online media such as online surveys. The implications of this uniformity are discussed, and three normative chronemic zones are identified.