Radiological-pathological correlation of pleomorphic liposarcoma of the anterior mediastinum in a 17-year-old girl

Liposarcoma is a soft-tissue sarcoma typically seen in adults. It is extremely rare in children. It most often occurs in the extremities or in the retroperitoneum. We present a very rare case of an anterior mediastinal liposarcoma of the pleomorphic subtype in a 17-year-old girl, along with radiological and pathological correlation. The location, patient age and histological subtype are exceedingly uncommon for this tumor

The NEWMEDS rodent touchscreen test battery for cognition relevant to schizophrenia.

RATIONALE: The NEWMEDS initiative (Novel Methods leading to New Medications in Depression and Schizophrenia, http://www.newmeds-europe.com ) is a large industrial-academic collaborative project aimed at developing new methods for drug discovery for schizophrenia. As part of this project, Work package 2 (WP02) has developed and validated a comprehensive battery of novel touchscreen tasks for rats and mice for assessing cognitive domains relevant to schizophrenia. OBJECTIVES: This article provides a review of the touchscreen battery of tasks for rats and mice for assessing cognitive domains relevant to schizophrenia and highlights validation data presented in several primary articles in this issue and elsewhere. METHODS: The battery consists of the five-choice serial reaction time task and a novel rodent continuous performance task for measuring attention, a three-stimulus visual reversal and the serial visual reversal task for measuring cognitive flexibility, novel non-matching to sample-based tasks for measuring spatial working memory and paired-associates learning for measuring long-term memory. RESULTS: The rodent (i.e. both rats and mice) touchscreen operant chamber and battery has high translational value across species due to its emphasis on construct as well as face validity. In addition, it offers cognitive profiling of models of diseases with cognitive symptoms (not limited to schizophrenia) through a battery approach, whereby multiple cognitive constructs can be measured using the same apparatus, enabling comparisons of performance across tasks. CONCLUSION: This battery of tests constitutes an extensive tool package for both model characterisation and pre-clinical drug discovery.This work was supported by the Innovative Medicine Initiative Joint Undertaking under grant agreement no. 115008 of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013). The authors thank Charlotte Oomen for valuable comments on the manuscript.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00213-015-4007-

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

A simplified study of trans-mitral Doppler patterns

<p>Abstract</p> <p>Background</p> <p>Trans-mitral Doppler produces complex patterns with a great deal of variability. There are several confusing numerical measures and indices to study these patterns. However trans-mitral Doppler produces readymade data visualization by pattern generation which could be interpreted by pattern analysis. By following a systematic approach we could create an order and use this tool to study cardiac function.</p> <p>Presentation of the hypothesis</p> <p>In this new approach we eliminate the variables and apply pattern recognition as the main criterion of study. Proper terminologies are also devised to avoid confusion. In this way we can get some meaningful information.</p> <p>Testing the hypothesis</p> <p>Trans-mitral Doppler should be seen as patterns rather than the amplitude. The hypothesis can be proven by logical deduction, extrapolation and elimination of variables. Trans-mitral flow is also analyzed <it>vis-à-vis </it>the Starling's Law applied to the left atrium.</p> <p>Implications of the hypothesis</p> <p>Trans-mitral Doppler patterns are not just useful for evaluating diastolic function. They are also useful to evaluate systolic function. By following this schema we could get useful diagnostic information and therapeutic options using simple pattern recognition with minimal measurements. This simplified but practical approach will be useful in day to day clinical practice and help in understanding cardiac function better. This will also standardize research and improve communication.</p

Phosphorylated Dihydroceramides from Common Human Bacteria Are Recovered in Human Tissues

Novel phosphorylated dihydroceramide (PDHC) lipids produced by the periodontal pathogen Porphyromonas gingivalis include phosphoethanolamine (PE DHC) and phosphoglycerol dihydroceramides (PG DHC) lipids. These PDHC lipids mediate cellular effects through Toll-like receptor 2 (TLR2) including promotion of IL-6 secretion from dendritic cells and inhibition of osteoblast differentiation and function in vitro and in vivo. The PE DHC lipids also enhance (TLR2)-dependent murine experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. The unique non-mammalian structures of these lipids allows for their specific quantification in bacteria and human tissues using multiple reaction monitoring (MRM)-mass spectrometry (MS). Synthesis of these lipids by other common human bacteria and the presence of these lipids in human tissues have not yet been determined. We now report that synthesis of these lipids can be attributed to a small number of intestinal and oral organisms within the Bacteroides, Parabacteroides, Prevotella, Tannerella and Porphyromonas genera. Additionally, the PDHCs are not only present in gingival tissues, but are also present in human blood, vasculature tissues and brain. Finally, the distribution of these TLR2-activating lipids in human tissues varies with both the tissue site and disease status of the tissue suggesting a role for PDHCs in human disease

Plasma concentrations of soluble IL-2 receptor α (CD25) are increased in type 1 diabetes and associated with reduced C-peptide levels in young patients.

AIMS/HYPOTHESIS: Type 1 diabetes is a common autoimmune disease that has genetic and environmental determinants. Variations within the IL2 and IL2RA (also known as CD25) gene regions are associated with disease risk, and variation in expression or function of these proteins is likely to be causal. We aimed to investigate if circulating concentrations of the soluble form of CD25, sCD25, an established marker of immune activation and inflammation, were increased in individuals with type 1 diabetes and if this was associated with the concentration of C-peptide, a measure of insulin production that reflects the degree of autoimmune destruction of the insulin-producing beta cells. METHODS: We used immunoassays to measure sCD25 and C-peptide in peripheral blood plasma from patient and control samples. RESULTS: We identified that sCD25 was increased in patients with type 1 diabetes compared with controls and replicated this result in an independent set of 86 adult patient and 80 age-matched control samples (p = 1.17 × 10(-3)). In 230 patients under 20 years of age, with median duration-of-disease of 6.1 years, concentrations of sCD25 were negatively associated with C-peptide concentrations (p = 4.8 × 10(-3)). CONCLUSIONS/INTERPRETATION: The 25% increase in sCD25 in patients, alongside the inverse association between sCD25 and C-peptide, probably reflect the adverse effects of an on-going, actively autoimmune and inflammatory immune system on beta cell function in patients

Transcriptional Response of Zebrafish Embryos Exposed to Neurotoxic Compounds Reveals a Muscle Activity Dependent hspb11 Expression

Acetylcholinesterase (AChE) inhibitors are widely used as pesticides and drugs. Their primary effect is the overstimulation of cholinergic receptors which results in an improper muscular function. During vertebrate embryonic development nerve activity and intracellular downstream events are critical for the regulation of muscle fiber formation. Whether AChE inhibitors and related neurotoxic compounds also provoke specific changes in gene transcription patterns during vertebrate development that allow them to establish a mechanistic link useful for identification of developmental toxicity pathways has, however, yet not been investigated. Therefore we examined the transcriptomic response of a known AChE inhibitor, the organophosphate azinphos-methyl (APM), in zebrafish embryos and compared the response with two non-AChE inhibiting unspecific control compounds, 1,4-dimethoxybenzene (DMB) and 2,4-dinitrophenol (DNP). A highly specific cluster of APM induced gene transcripts was identified and a subset of strongly regulated genes was analyzed in more detail. The small heat shock protein hspb11 was found to be the most sensitive induced gene in response to AChE inhibitors. Comparison of expression in wildtype, ache and sopfixe mutant embryos revealed that hspb11 expression was dependent on the nicotinic acetylcholine receptor (nAChR) activity. Furthermore, modulators of intracellular calcium levels within the whole embryo led to a transcriptional up-regulation of hspb11 which suggests that elevated intracellular calcium levels may regulate the expression of this gene. During early zebrafish development, hspb11 was specifically expressed in muscle pioneer cells and Hspb11 morpholino-knockdown resulted in effects on slow muscle myosin organization. Our findings imply that a comparative toxicogenomic approach and functional analysis can lead to the identification of molecular mechanisms and specific marker genes for potential neurotoxic compounds

Crime, Policing and Compliance with the Law

Social scientific research has made a very substantial contribution to specialist academic understanding of crime and its control. This chapter sketches out that contribution that has been made in three areas: our understanding of crime trends; our knowledge of policing and its effects of crime; and the factors that encourage people to comply with the law. The ways in which practitioners and academics think about these issues has been transformed over the last half-century, and social scientific research is a significant factor in achieving this transformation. However, the same research has achieved a much more tenuous hold on political and public discourse about crime, and the chapter concludes with a discussion of the reasons for this, and offers some thoughts on how social science should aim to extend its reach into highly politicised issues such as “law and order”

Turning Males On: Activation of Male Courtship Behavior in Drosophila melanogaster

The innate sexual behaviors of Drosophila melanogaster males are an attractive system for elucidating how complex behavior patterns are generated. The potential for male sexual behavior in D. melanogaster is specified by the fruitless (fru) and doublesex (dsx) sex regulatory genes. We used the temperature-sensitive activator dTRPA1 to probe the roles of fruM- and dsx-expressing neurons in male courtship behaviors. Almost all steps of courtship, from courtship song to ejaculation, can be induced at very high levels through activation of either all fruM or all dsx neurons in solitary males. Detailed characterizations reveal different roles for fruM and dsx in male courtship. Surprisingly, the system for mate discrimination still works well when all dsx neurons are activated, but is impaired when all fruM neurons are activated. Most strikingly, we provide evidence for a fruM-independent courtship pathway that is primarily vision dependent

Diastolic time – frequency relation in the stress echo lab: filling timing and flow at different heart rates

A cutaneous force-frequency relation recording system based on first heart sound amplitude vibrations has been recently validated. Second heart sound can be simultaneously recorded in order to quantify both systole and diastole duration