Delayed Severe Drug Induced Cholestasis After Anabolic Steroids Exposure

Anabolic steroids therapy is linked to a distinctive form of acute cholestasis that generally arises within 1 to 4 months of starting therapy but may be delayed to as long as 6 to 24 months in some reported cases. We are presenting an unusual case where acute cholestasis happened 5 weeks after discontinuing short course (7 days) of anabolic steroids. A 20-year-old African American male without significant past medical history presented with jaundice, mild nausea and generalized pruritis. He admitted to self-initiation of oral Stanozolol 40 mg daily for 7-days about 5 weeks before his admission. No prior incidence and no significant alcohol use. Vitals signs unremarkable and physical exam was unremarkable except for jaundice and sclera icterus. No hepatosplenomegaly. Liver function profile with ALT 44 IU/L, AST 72 IU/L, ALP 266 IU/L, & total bilirubin of 21.4 mg/Dl. Extensive hepatitis workup was negative and a CT-guided liver biopsy was performed which showed marked hepatocanalicular cholestasis. This is reflective of drug induced cholestasis. Our case highlights the possibility of delayed liver injury even after a short anabolic steroids course which typically happen while taking the medication for an extended period (more than 1 month)

Young people’s orientations to the future: navigating the present and imagining the future

This article discusses the findings of the Imagine Sheppey project (2013-14) which studied how young people are ‘oriented’ towards the future. The aim and approach of the project was to explore future imaginaries in a participatory, experimental, and performative way. Working with young people in a series of arts-based workshops, we intervened in different environments to alter the space as an experience of change – temporal, material, symbolic. We documented this process visually and made use of the images produced as the basis for elicitation in focus groups with a wider group of young people. In this article we discuss young people’s future orientations through the themes of reach, resources, shape, and value. In so doing, we reflect on the paths that our young respondents traced to connect their presents to what is next, what we call their modes of present-future navigation. We explore the qualities and characteristics of their stances within a wider reflection about how young people approach, imagine and account for the future

Living with the h-index? Metric assemblages in the contemporary academy

This paper examines the relationship between metrics, markets and affect in the contemporary UK academy. It argues that the emergence of a particular structure of feeling amongst academics in the last few years has been closely associated with the growth and development of ‘quantified control’. It examines the functioning of a range of metrics: citations; workload models; transparent costing data; research assessments; teaching quality assessments; and commercial university league tables. It argues that these metrics, and others, although still embedded within an audit culture, increasingly function autonomously as a data assemblage able not just to mimic markets but, increasingly, to enact them. It concludes by posing some questions about the possible implications of this for the future of academic practice

Exploring the pastiche hegemony of men

In this article I explore the continued hegemony of certain men. I use interview extracts to help think through the notion of pastiche hegemony as a means of understanding how men, and narratives about them, have changed, but unequal power relations persist. In particular, I explore this process within men’s understandings of how they were able to gain and maintain influence and power at work. Through their reflexive reading of the changing shape of late modern Western society, these men believed they were able to craft selves and employ social scripts to produce social influence and power in situational and contingent forms. I argue that it is within this interactional process that the increasingly undermined ideological and material legacy of patriarchy might still be reified. As such, while there is clear evidence highlighting the undermining of men’s ability to assume power, within this article I theoretically unpack how certain men might be able to produce a localized, pastiche hegemony. This article is published as part of a thematic collection on gender studies

Global Systems-Level Analysis of Hfq and SmpB Deletion Mutants in Salmonella: Implications for Virulence and Global Protein Translation

Using sample-matched transcriptomics and proteomics measurements it is now possible to begin to understand the impact of post-transcriptional regulatory programs in Enterobacteria. In bacteria post-transcriptional regulation is mediated by relatively few identified RNA-binding protein factors including CsrA, Hfq and SmpB. A mutation in any one of these three genes, csrA, hfq, and smpB, in Salmonella is attenuated for mouse virulence and unable to survive in macrophages. CsrA has a clearly defined specificity based on binding to a specific mRNA sequence to inhibit translation. However, the proteins regulated by Hfq and SmpB are not as clearly defined. Previous work identified proteins regulated by hfq using purification of the RNA-protein complex with direct sequencing of the bound RNAs and found binding to a surprisingly large number of transcripts. In this report we have used global proteomics to directly identify proteins regulated by Hfq or SmpB by comparing protein abundance in the parent and isogenic hfq or smpB mutant. From these same samples we also prepared RNA for microarray analysis to determine if alteration of protein expression was mediated post-transcriptionally. Samples were analyzed from bacteria grown under four different conditions; two laboratory conditions and two that are thought to mimic the intracellular environment. We show that mutants of hfq and smpB directly or indirectly modulate at least 20% and 4% of all possible Salmonella proteins, respectively, with limited correlation between transcription and protein expression. These proteins represent a broad spectrum of Salmonella proteins required for many biological processes including host cell invasion, motility, central metabolism, LPS biosynthesis, two-component regulatory systems, and fatty acid metabolism. Our results represent one of the first global analyses of post-transcriptional regulons in any organism and suggest that regulation at the translational level is widespread and plays an important role in virulence regulation and environmental adaptation for Salmonella

Genome-Scale Modeling of Light-Driven Reductant Partitioning and Carbon Fluxes in Diazotrophic Unicellular Cyanobacterium Cyanothece sp. ATCC 51142

Genome-scale metabolic models have proven useful for answering fundamental questions about metabolic capabilities of a variety of microorganisms, as well as informing their metabolic engineering. However, only a few models are available for oxygenic photosynthetic microorganisms, particularly in cyanobacteria in which photosynthetic and respiratory electron transport chains (ETC) share components. We addressed the complexity of cyanobacterial ETC by developing a genome-scale model for the diazotrophic cyanobacterium, Cyanothece sp. ATCC 51142. The resulting metabolic reconstruction, iCce806, consists of 806 genes associated with 667 metabolic reactions and includes a detailed representation of the ETC and a biomass equation based on experimental measurements. Both computational and experimental approaches were used to investigate light-driven metabolism in Cyanothece sp. ATCC 51142, with a particular focus on reductant production and partitioning within the ETC. The simulation results suggest that growth and metabolic flux distributions are substantially impacted by the relative amounts of light going into the individual photosystems. When growth is limited by the flux through photosystem I, terminal respiratory oxidases are predicted to be an important mechanism for removing excess reductant. Similarly, under photosystem II flux limitation, excess electron carriers must be removed via cyclic electron transport. Furthermore, in silico calculations were in good quantitative agreement with the measured growth rates whereas predictions of reaction usage were qualitatively consistent with protein and mRNA expression data, which we used to further improve the resolution of intracellular flux values

Mammal-Like Organization of the Avian Midbrain Central Gray and a Reappraisal of the Intercollicular Nucleus

In mammals, rostrocaudal columns of the midbrain periaqueductal gray (PAG) regulate diverse behavioral and physiological functions, including sexual and fight-or-flight behavior, but homologous columns have not been identified in non-mammalian species. In contrast to mammals, in which the PAG lies ventral to the superior colliculus and surrounds the cerebral aqueduct, birds exhibit a hypertrophied tectum that is displaced laterally, and thus the midbrain central gray (CG) extends mediolaterally rather than dorsoventrally as in mammals. We therefore hypothesized that the avian CG is organized much like a folded open PAG. To address this hypothesis, we conducted immunohistochemical comparisons of the midbrains of mice and finches, as well as Fos studies of aggressive dominance, subordinance, non-social defense and sexual behavior in territorial and gregarious finch species. We obtained excellent support for our predictions based on the folded open model of the PAG and further showed that birds possess functional and anatomical zones that form longitudinal columns similar to those in mammals. However, distinguishing characteristics of the dorsal/dorsolateral PAG, such as a dense peptidergic innervation, a longitudinal column of neuronal nitric oxide synthase neurons, and aggression-induced Fos responses, do not lie within the classical avian CG, but in the laterally adjacent intercollicular nucleus (ICo), suggesting that much of the ICo is homologous to the dorsal PAG

Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms

Objective: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. Method: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. Results: The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, n(effective) = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (vertical bar r(g)vertical bar > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range vertical bar r(g)vertical bar = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Conclusion: Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.Peer reviewe