Sibling comparisons elucidate the associations between educational attainment polygenic scores and alcohol, nicotine and cannabis.

Background and aimsThe associations between low educational attainment and substance use disorders (SUDs) may be related to a common genetic vulnerability. We aimed to elucidate the associations between polygenic scores for educational attainment and clinical criterion counts for three SUDs (alcohol, nicotine and cannabis).DesignPolygenic association and sibling comparison methods. The latter strengthens inferences in observational research by controlling for confounding factors that differ between families.SettingSix sites in the United States.ParticipantsEuropean ancestry participants aged 25 years and older from the Collaborative Study on the Genetics of Alcoholism (COGA). Polygenic association analyses included 5582 (54% female) participants. Sibling comparisons included 3098 (52% female) participants from 1226 sibling groups nested within the overall sample.MeasurementsOutcomes included criterion counts for DSM-5 alcohol use disorder (AUDSX), Fagerström nicotine dependence (NDSX) and DSM-5 cannabis use disorder (CUDSX). We derived polygenic scores for educational attainment (EduYears-GPS) using summary statistics from a large (> 1 million) genome-wide association study of educational attainment.FindingsIn polygenic association analyses, higher EduYears-GPS predicted lower AUDSX, NDSX and CUDSX [P < 0.01, effect sizes (R2 ) ranging from 0.30 to 1.84%]. These effects were robust in sibling comparisons, where sibling differences in EduYears-GPS predicted all three SUDs (P < 0.05, R2 0.13-0.20%).ConclusionsIndividuals who carry more alleles associated with educational attainment tend to meet fewer clinical criteria for alcohol, nicotine and cannabis use disorders, and these effects are robust to rigorous controls for potentially confounding factors that differ between families (e.g. socio-economic status, urban-rural residency and parental education)

Leiomyosarcoma of the inferior vena cava: a case report and review of the literature

A 68-year-old white female presented with two years of progressively worsening dyspnea. Echocardiography revealed a large right atrial mass and partial obstruction of the inferior vena cava. Further imaging revealed a cystic dense mass in the inferior vena cava and right atrium. Immunohistochemical stains were consistent with leiomyosarcoma. Intraoperatively, the tumor was noted to originate from the posterior aspect of the inferior vena cava. The patient underwent successful resection of the mass. Adjuvant radiation therapy was completed. The patient's dyspnea gradually improved and she continues to remain disease free five years post-resection

An ECF-type transporter scavenges heme to overcome iron-limitation in Staphylococcus lugdunensis

Energy-coupling factor type transporters (ECF) represent trace nutrient acquisition systems. Substrate binding components of ECF-transporters are membrane proteins with extraordinary affinity, allowing them to scavenge trace amounts of ligand. A number of molecules have been described as substrates of ECF-transporters, but an involvement in iron-acquisition is unknown. Host-induced iron limitation during infection represents an effective mechanism to limit bacterial proliferation. We identified the iron-regulated ECF-transporter Lha in the opportunistic bacterial pathogen Staphylococcus lugdunensis and show that the transporter is specific for heme. The recombinant substrate-specific subunit LhaS accepted heme from diverse host-derived hemoproteins. Using isogenic mutants and recombinant expression of Lha, we demonstrate that its function is independent of the canonical heme acquisition system Isd and allows proliferation on human cells as sources of nutrient iron. Our findings reveal a unique strategy of nutritional heme acquisition and provide the first example of an ECF-transporter involved in overcoming host-induced nutritional limitation

Deep and Comparative Transcriptome Analysis of Rice Plants Infested by the Beet Armyworm (\u3ci\u3eSpodoptera exigua\u3c/i\u3e) and Water Weevil (\u3ci\u3eLissorhoptrus oryzophilus\u3c/i\u3e)

The beet armyworm (Spodoptera exigua) and the rice water weevil (Lissorhoptrus oryzophilus) are two important insect pests in rice production. To identify insect-responsive genes in rice, we performed a deep transcriptome analysis of Nipponbare rice leaves infested with both beet armyworm and water weevil using massively parallel signature sequencing (MPSS). Many antisense, alternative, and novel transcripts were commonly and specifically induced and suppressed in the infested tissue. Key genes involved in the defense metabolic pathways such as salicylic acid and jasmonic acid biosynthesis pathways were up-regulated in the infested leaves. To validate theMPSS results, we analyzed the transcriptome of the rice leaves infested with water weevils using Solexa’s sequencing-bysynthesis (SBS) method. The MPSS and SBS data were highly correlated (Pearson’s correlation coefficient=0.85), and 83% of genes had similar gene expression in both libraries. Our comprehensive and in-depth survey of the insect-infested libraries provides a rich genomic resource for further analyzing the function of key regulatory genes involved in insect resistance in rice. Supplementary files are attached below

Genome-wide variation and transcriptional changes in diverse developmental processes underlie the rapid evolution of seasonal adaptation

Many organisms enter a dormant state in their life cycle to deal with predictable changes in environments over the course of a year. The timing of dormancy is therefore a key seasonal adaptation, and it evolves rapidly with changing environments. We tested the hypothesis that differences in the timing of seasonal activity are driven by differences in the rate of development during diapause in Rhagoletis pomonella, a fly specialized to feed on fruits of seasonally limited host plants. Transcriptomes from the central nervous system across a time series during diapause show consistent and progressive changes in transcripts participating in diverse developmental processes, despite a lack of gross morphological change. Moreover, population genomic analyses suggested that many genes of small effect enriched in developmental functional categories underlie variation in dormancy timing and overlap with gene sets associated with development rate in Drosophila melanogaster. Our transcriptional data also suggested that a recent evolutionary shift from a seasonally late to a seasonally early host plant drove more rapid development during diapause in the early fly population. Moreover, genetic variants that diverged during the evolutionary shift were also enriched in putative cis regulatory regions of genes differentially expressed during diapause development. Overall, our data suggest polygenic variation in the rate of developmental progression during diapause contributes to the evolution of seasonality in R. pomonella. We further discuss patterns that suggest hourglass-like developmental divergence early and late in diapause development and an important role for hub genes in the evolution of transcriptional divergence

Joint Statement on Pediatric Education at Schools of Pharmacy

Providing health care for children is a unique specialty, and pediatric patients represent approximately 25% of the population. Education of pharmacy students on patients across the lifespan is required by current Accreditation Council for Pharmacy Education standards and outcomes; thus, it is essential that pharmacy students gain a proficiency in caring for children. A collaborative panel of pediatric faculty members from schools and colleges of pharmacy was established to review the current literature regarding pediatric education in Doctor of Pharmacy curricula and establish updated recommendations for the provision of pediatric pharmacy education. This statement outlines five recommendations supporting inclusion of pediatric content and skills in Doctor of Pharmacy curricula

HSD3B1 genotype identifies glucocorticoid responsiveness in severe asthma

Asthma resistance to glucocorticoid treatment is a major health problem with unclear etiology. Glucocorticoids inhibit adrenal androgen production. However, androgens have potential benefits in asthma. HSD3B1 encodes for 3β-hydroxysteroid dehydrogenase-1 (3β-HSD1), which catalyzes peripheral conversion from adrenal dehydroepiandrosterone (DHEA) to potent androgens and has a germline missense-encoding polymorphism. The adrenal restrictive HSD3B1(1245A) allele limits conversion, whereas the adrenal permissive HSD3B1(1245C) allele increases DHEA metabolism to potent androgens. In the Severe Asthma Research Program (SARP) III cohort, we determined the association between DHEA-sulfate and percentage predicted forced expiratory volume in 1 s (FEV1PP). HSD3B1(1245) genotypes were assessed, and association between adrenal restrictive and adrenal permissive alleles and FEV1PP in patients with (GC) and without (noGC) daily oral glucocorticoid treatment was determined (n = 318). Validation was performed in a second cohort (SARP I&II; n = 184). DHEA-sulfate is associated with FEV1PP and is suppressed with GC treatment. GC patients homozygous for the adrenal restrictive genotype have lower FEV1PP compared with noGC patients (54.3% vs. 75.1%; P < 0.001). In patients with the homozygous adrenal permissive genotype, there was no FEV1PP difference in GC vs. noGC patients (73.4% vs. 78.9%; P = 0.39). Results were independently confirmed: FEV1PP for homozygous adrenal restrictive genotype in GC vs. noGC is 49.8 vs. 63.4 (P < 0.001), and for homozygous adrenal permissive genotype, it is 66.7 vs. 67.7 (P = 0.92). The adrenal restrictive HSD3B1(1245) genotype is associated with GC resistance. This effect appears to be driven by GC suppression of 3β-HSD1 substrate. Our results suggest opportunities for prediction of GC resistance and pharmacologic intervention

Unique and conserved MicroRNAs in wheat chromosome 5D revealed by next-generation sequencing

MicroRNAs are a class of short, non-coding, single-stranded RNAs that act as post-transcriptional regulators in gene expression. miRNA analysis of Triticum aestivum chromosome 5D was performed on 454 GS FLX Titanium sequences of flow sorted chromosome 5D with a total of 3,208,630 good quality reads representing 1.34x and 1.61x coverage of the short (5DS) and long (5DL) arms of the chromosome respectively. In silico and structural analyses revealed a total of 55 miRNAs; 48 and 42 miRNAs were found to be present on 5DL and 5DS respectively, of which 35 were common to both chromosome arms, while 13 miRNAs were specific to 5DL and 7 miRNAs were specific to 5DS. In total, 14 of the predicted miRNAs were identified in wheat for the first time. Representation (the copy number of each miRNA) was also found to be higher in 5DL (1,949) compared to 5DS (1,191). Targets were predicted for each miRNA, while expression analysis gave evidence of expression for 6 out of 55 miRNAs. Occurrences of the same miRNAs were also found in Brachypodium distachyon and Oryza sativa genome sequences to identify syntenic miRNA coding sequences. Based on this analysis, two other miRNAs: miR1133 and miR167 were detected in B. distachyon syntenic region of wheat 5DS. Five of the predicted miRNA coding regions (miR6220, miR5070, miR169, miR5085, miR2118) were experimentally verified to be located to the 5D chromosome and three of them : miR2118, miR169 and miR5085, were shown to be 5D specific. Furthermore miR2118 was shown to be expressed in Chinese Spring adult leaves. miRNA genes identified in this study will expand our understanding of gene regulation in bread wheat

Economic burden and comorbidities of attention-deficit/hyperactivity disorder among pediatric patients hospitalized in the United States

<p>Abstract</p> <p>Background</p> <p>This retrospective database analysis used data from the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (NIS) to examine common primary diagnoses among children and adolescents hospitalized with a secondary diagnosis of attention- deficit/hyperactivity disorder (ADHD) and assessed the burden of ADHD.</p> <p>Methods</p> <p>Hospitalized children (aged 6-11 years) and adolescents (aged 12-17 years) with a secondary diagnosis of ADHD were identified. The 10 most common primary diagnoses (using the first 3 digits of the ICD-9-CM code) were reported for each age group. Patients with 1 of these conditions were selected to analyze demographics, length of stay (LOS), and costs. Control patients were selected if they had 1 of the 10 primary diagnoses and no secondary ADHD diagnosis. Patient and hospital characteristics were reported by cohort (i.e., patients with ADHD vs. controls), and LOS and costs were reported by primary diagnosis. Multivariable linear regression analyses were undertaken to adjust LOS and costs based on patient and hospital characteristics.</p> <p>Results</p> <p>A total of 126,056 children and 204,176 adolescents were identified as having a secondary diagnosis of ADHD. Among children and adolescents with ADHD, the most common diagnoses tended to be mental health related (i.e., affective psychoses, emotional disturbances, conduct disturbances, depressive disorder, or adjustment reaction). Other common diagnoses included general symptoms, asthma (in children only), and acute appendicitis. Among patients with ADHD, a higher percentage were male, white, and covered by Medicaid. LOS and costs were higher among children with ADHD and a primary diagnosis of affective psychoses (by 0.61 days and $51), adjustment reaction (by 1.71 days and$940), or depressive disorder (by 0.41 days and $124) versus controls. LOS and costs were higher among adolescents with ADHD and a primary diagnosis of affective psychoses (by 1.04 days and$352), depressive disorder (by 0.94 days and $517), conduct disturbances (by 0.86 days and$1,330), emotional disturbances (by 1.45 days and $1,626), adjustment reaction (by 1.25 days and$702), and neurotic disorders (by 1.60 days and $541) versus controls.</p> <p>Conclusion</p> <p>Clinicians and health care decision makers should be aware of the potential impact of ADHD on hospitalized children and adolescents.</p