Genotype, Childhood Maltreatment, and Their Interaction in the Etiology of Adult Antisocial Behaviors

BACKGROUND: Maltreatment by an adult or caregiver during childhood is a prevalent and important predictor of antisocial behaviors in adulthood. A functional promoter polymorphism in the monoamine oxidase A (MAOA) gene has been implicated as a moderating factor in the relationship between childhood maltreatment and antisocial behaviors. Although there have been numerous attempts at replicating this observation, results remain inconclusive. METHODS: We examined this gene-environment interaction hypothesis in a sample of 3356 white and 960 black men (aged 24-34) participating in the National Longitudinal Study of Adolescent Health. RESULTS: Primary analysis indicated that childhood maltreatment was a significant risk factor for later behaviors that violate rules and the rights of others (p .05). Power analyses indicated that these results were not due to insufficient statistical power. CONCLUSIONS: We could not confirm the hypothesis that MAOA genotype moderates the relationship between childhood maltreatment and adult antisocial behaviors

Depression, Stressful Life Events, and the Impact of Variation in the Serotonin Transporter: Findings from the National Longitudinal Study of Adolescent to Adult Health (Add Health)

BackgroundThe low transcriptionally efficient short-allele of the 5HTTLPR serotonin transporter polymorphism has been implicated to moderate the relationship between the experience of stressful life events (SLEs) and depression. Despite numerous attempts at replicating this observation, results remain inconclusive.MethodsWe examined this relationship in young-adult Non-Hispanic white males and females between the ages of 22 and 26 (n = 4724) participating in the National Longitudinal Study of Adolescent to Adult Health (Add Health) with follow-up information every six years since 1995.ResultsLinear and logistic regression models, corrected for multiple testing, indicated that carriers of one or more of the S-alleles were more sensitive to stress than those with two L-alleles and at a higher risk for depression. This relationship behaved in a dose-response manner such that the risk for depression was greatest among those who reported experiencing higher numbers of SLEs. In post-hoc analyses we were not able to replicate an interaction effect for suicide ideation but did find suggestive evidence that the effects of SLEs and 5HTTLPR on suicide ideation differed for males and females. There were no effects of childhood maltreatment.DiscussionOur results provide partial support for the original hypothesis that 5-HTTLPR genotype interacts with the experience of stressful life events in the etiology of depression during young adulthood. However, even with this large sample, and a carefully constructed a priori analysis plan, the results were still not definitive. For the purposes of replication, characterizing the 5HTTLPR in other large data sets with extensive environmental and depression measures is needed

Genomic and Metabolomic Insights into the Natural Product Biosynthetic Diversity of a Feral-Hog-Associated Brevibacillus laterosporus Strain

The authors thank C. A. Mitchell for advice concerning the organization of the biosynthetic gene clusters in B. laterosporus PE36. We acknowledge J. Villemarete for providing access to the feral hog for sampling. Author contributions Conceived and designed the experiments: BSS RHC. Performed the experiments: CMT BWS JBK LSLP DRP. Analyzed the data: CMT BWS JBK LSLP DRP BSS RHC. Contributed reagents/materials/analysis tools: CMT BWS DRP. Wrote the paper: CMT BWS BSS RHC.Bacteria associated with mammals are a rich source of microbial biodiversity; however, little is known concerning the abilities of these microbes to generate secondary metabolites. This report focuses on a bacterium isolated from the ear of a feral hog from southwestern Oklahoma, USA. The bacterium was identified as a new strain (PE36) of Brevibacillus latersporus, which was shown via genomic analysis to contain a large number of gene clusters presumably involved in secondary metabolite biosynthesis. A scale-up culture of B. latersporus PE36 yielded three bioactive compounds that inhibited the growth of methicillin-resistant Staphylococcus aureus (basiliskamides A and B and 12-methyltetradecanoic acid). Further studies of the isolate's secondary metabolome provided both new (auripyrazine) and previously-described pyrazine-containing compounds. In addition, a new peptidic natural product (auriporcine) was purified that was determined to be composed of a polyketide unit, two L-proline residues, two D-leucine residues, one L-leucine residue, and a reduced L-phenylalanine (L-phenylalanol). An examination of the genome revealed two gene clusters that are likely responsible for generating the basiliskamides and auriporcine. These combined genomic and chemical studies confirm that new and unusual secondary metabolites can be obtained from the bacterial associates of wild mammals.Ye

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Unstandardized Logistic Regression Estimates and Standard Errors Predicting Depression and Suicide Ideation.

<p>Unstandardized Logistic Regression Estimates and Standard Errors Predicting Depression and Suicide Ideation.</p