Diffusion-weighted MRI in acute spinal cord ischaemia

Abstract : Acute spinal cord ischaemia is often undetectable with conventional MRI. Diffusion-weighted MRI (DWI) has been difficult to use in the spine because of susceptibility artefacts. We assessed the diagnostic value of echoplanar DWI for early confirmation of spinal cord ischaemia. We performed conventional MRI and DWI in two men and three women, aged 54-75years with clinically suspected acute spinal cord ischaemia. Imaging was performed 9-46h after the onset of symptoms, and 2-9days later to assess the extent of ischaemic signal change. Spatial resolution of DWI within the spine using standard equipment was poor, but in all patients, early DWI revealed areas of high signal indicating decreased diffusion, confirmed by measurement of apparent diffusion coefficients. Follow-up MRI showed high signal on T2-weighted images and contrast enhancement at the expected levels. Neurological deficits corresponded with radiological findings in four patients: various syndromes, including isolated bilateral weakness or sensory change and combined deficits, were found. Echoplanar DWI may be helpful for confirmation of spinal cord ischaemia in the acute stage, but follow-up T2-weighted images have superior spatial resolution and correlation with clinical findings and lesion exten

Consequential considerations when mapping tRNA fragments

We examine several of the choices that went into the design of tDRmapper, a recently reported tool for identifying transfer RNA (tRNA) fragments in deep sequencing data, evaluate them in the context of currently available knowledge, and discuss their potential impact on the output that the tool generates

The complex transcriptional landscape of the anucleate human platelet.

BACKGROUND: Human blood platelets are essential to maintaining normal hemostasis, and platelet dysfunction often causes bleeding or thrombosis. Estimates of genome-wide platelet RNA expression using microarrays have provided insights to the platelet transcriptome but were limited by the number of known transcripts. The goal of this effort was to deep-sequence RNA from leukocyte-depleted platelets to capture the complex profile of all expressed transcripts. RESULTS: From each of four healthy individuals we generated long RNA (≥40 nucleotides) profiles from total and ribosomal-RNA depleted RNA preparations, as well as short RNA (\u3c40 \u3enucleotides) profiles. Analysis of ~1 billion reads revealed that coding and non-coding platelet transcripts span a very wide dynamic range (≥16 PCR cycles beyond β-actin), a result we validated through qRT-PCR on many dozens of platelet messenger RNAs. Surprisingly, ribosomal-RNA depletion significantly and adversely affected estimates of the relative abundance of transcripts. Of the known protein-coding loci, ~9,500 are present in human platelets. We observed a strong correlation between mRNAs identified by RNA-seq and microarray for well-expressed mRNAs, but RNASeq identified many more transcripts of lower abundance and permitted discovery of novel transcripts. CONCLUSIONS: Our analyses revealed diverse classes of non-coding RNAs, including: pervasive antisense transcripts to protein-coding loci; numerous, previously unreported and abundant microRNAs; retrotransposons; and thousands of novel un-annotated long and short intronic transcripts, an intriguing finding considering the anucleate nature of platelets. The data are available through a local mirror of the UCSC genome browser and can be accessed at: http://cm.jefferson.edu/platelets_2012/

The selective phosphodiesterase 4 inhibitor roflumilast and phosphodiesterase 3/4 inhibitor pumafentrine reduce clinical score and TNF expression in experimental colitis in mice.

The specific inhibition of phosphodiesterase (PDE)4 and dual inhibition of PDE3 and PDE4 has been shown to decrease inflammation by suppression of pro-inflammatory cytokine synthesis. We examined the effect of roflumilast, a selective PDE4 inhibitor marketed for severe COPD, and the investigational compound pumafentrine, a dual PDE3/PDE4 inhibitor, in the preventive dextran sodium sulfate (DSS)-induced colitis model. The clinical score, colon length, histologic score and colon cytokine production from mice with DSS-induced colitis (3.5% DSS in drinking water for 11 days) receiving either roflumilast (1 or 5 mg/kg body weight/d p.o.) or pumafentrine (1.5 or 5 mg/kg/d p.o.) were determined and compared to vehicle treated control mice. In the pumafentrine-treated animals, splenocytes were analyzed for interferon-γ (IFNγ) production and CD69 expression. Roflumilast treatment resulted in dose-dependent improvements of clinical score (weight loss, stool consistency and bleeding), colon length, and local tumor necrosis factor-α (TNFα) production in the colonic tissue. These findings, however, were not associated with an improvement of the histologic score. Administration of pumafentrine at 5 mg/kg/d alleviated the clinical score, the colon length shortening, and local TNFα production. In vitro stimulated splenocytes after in vivo treatment with pumafentrine showed a significantly lower state of activation and production of IFNγ compared to no treatment in vivo. These series of experiments document the ameliorating effect of roflumilast and pumafentrine on the clinical score and TNF expression of experimental colitis in mice

Ejaculate Economics: Testing the Effects of Male Sexual History on the Trade-Off between Sperm and Immune Function in Australian Crickets

Trade-offs between investment into male sexual traits and immune function provide the foundation for some of the most prominent models of sexual selection. Post-copulatory sexual selection on the male ejaculate is intense, and therefore trade-offs should occur between investment into the ejaculate and the immune system. Examples of such trade-offs exist, including that between sperm quality and immunity in the Australian cricket, Teleogryllus oceanicus. Here, we explore the dynamics of this trade-off, examining the effects that increased levels of sexual interaction have on the viability of a male's sperm across time, and the concomitant effects on immune function. Males were assigned to a treatment, whereby they cohabited with females that were sexually immature, sexually mature but incapable of copulation, or sexually mature and capable of copulation. Sperm viability of each male was then assessed at two time points: six and 13 days into the treatment, and immune function at day 13. Sperm viability decreased across the time points, but only for males exposed to treatment classes involving sexually mature females. This decrease was similar in magnitude across both sexually mature classes, indicating that costs to the expression of high sperm viability are incurred largely through levels of pre-copulatory investment. Males exposed to immature females produced sperm of low viability at both time points. Although we confirmed a weak negative association between sperm viability and lytic activity (a measure of immune response to bacterial infection) at day 13, this relationship was not altered across the mating treatment. Our results highlight that sperm viability is a labile trait, costly to produce, and subject to strategic allocation in these crickets

Dystonia in neurodegeneration with brain iron accumulation: outcome of bilateral pallidal stimulation

Neurodegeneration with brain iron accumulation encompasses a heterogeneous group of rare neurodegenerative disorders that are characterized by iron accumulation in the brain. Severe generalized dystonia is frequently a prominent symptom and can be very disabling, causing gait impairment, difficulty with speech and swallowing, pain and respiratory distress. Several case reports and one case series have been published concerning therapeutic outcome of pallidal deep brain stimulation in dystonia caused by neurodegeneration with brain iron degeneration, reporting mostly favourable outcomes. However, with case studies, there may be a reporting bias towards favourable outcome. Thus, we undertook this multi-centre retrospective study to gather worldwide experiences with bilateral pallidal deep brain stimulation in patients with neurodegeneration with brain iron accumulation. A total of 16 centres contributed 23 patients with confirmed neurodegeneration with brain iron accumulation and bilateral pallidal deep brain stimulation. Patient details including gender, age at onset, age at operation, genetic status, magnetic resonance imaging status, history and clinical findings were requested. Data on severity of dystonia (Burke Fahn Marsden Dystonia Rating Scale—Motor Scale, Barry Albright Dystonia Scale), disability (Burke Fahn Marsden Dystonia Rating Scale—Disability Scale), quality of life (subjective global rating from 1 to 10 obtained retrospectively from patient and caregiver) as well as data on supportive therapy, concurrent pharmacotherapy, stimulation settings, adverse events and side effects were collected. Data were collected once preoperatively and at 2–6 and 9–15 months postoperatively. The primary outcome measure was change in severity of dystonia. The mean improvement in severity of dystonia was 28.5% at 2–6 months and 25.7% at 9–15 months. At 9–15 months postoperatively, 66.7% of patients showed an improvement of 20% or more in severity of dystonia, and 31.3% showed an improvement of 20% or more in disability. Global quality of life ratings showed a median improvement of 83.3% at 9–15 months. Severity of dystonia preoperatively and disease duration predicted improvement in severity of dystonia at 2–6 months; this failed to reach significance at 9–15 months. The study confirms that dystonia in neurodegeneration with brain iron accumulation improves with bilateral pallidal deep brain stimulation, although this improvement is not as great as the benefit reported in patients with primary generalized dystonias or some other secondary dystonias. The patients with more severe dystonia seem to benefit more. A well-controlled, multi-centre prospective study is necessary to enable evidence-based therapeutic decisions and better predict therapeutic outcomes

Phonotactic response of female crickets on the Kramer treadmill: methodology, sensory and behavioural implications

Since population-level variation in female mating preferences can shape intraspecific communication systems within the context of sexual selection it is essential to quantify these preferences and their sources of variation. We calculated individual female response functions for four male calling song traits in the field cricket Gryllus bimaculatus, by performing untethered phonotaxis measurements on a spherical locomotor compensator (Kramer treadmill). Firstly, we quantify the population-level sources of phonotactic variation and correct for factors that adversely affect this measurement. Secondly, we develop methodology for the characterisation of individual female phonotactic response functions suitable for population-level analyses and demonstrate the applicability of our method with respect to recent literature on Orthopteran acoustic communication. Phonotaxis towards a preferred stimulus on different occasions is highly repeatable, with lower repeatabilities away from the most preferred signal traits. For certain male signal traits, female preference and selectivity are highly repeatable. Although phonotactic response magnitude deteriorated with age, preference functions of females remained the same during their lifetimes. Finally, the limitations of measuring phonotaxis using a spherical locomotor compensator are described and discussed with respect to the estimation of the selectivity of female response

Prospective Environmental Life Cycle Assessment of Nanosilver T-Shirts

A cradle-to-grave life cycle assessment (LCA) is performed to compare nanosilver T-shirts with conventional T-shirts with and without biocidal treatment. For nanosilver production and textile incorporation, we investigate two processes: flame spray pyrolysis (FSP) and plasma polymerization with silver co-sputtering (PlaSpu). Prospective environmental impacts due to increased nanosilver T-shirt commercialization are estimated with six scenarios. Results show significant differences in environmental burdens between nanoparticle production technologies: The "cradle-to-gate" climate footprint of the production of a nanosilver T-shirt is 2.70 kg of CO2-equiv (FSP) and 7.67-166 kg of CO2-equiv (PlaSpu, varying maturity stages). Production of conventional T-shirts with and without the biocide triclosan has emissions of 2.55 kg of CO2-equiv (contribution from triclosan insignificant). Consumer behavior considerably affects the environmental impacts during the use phase. Lower washing frequencies can compensate for the increased climate footprint of FSP nanosilver T-shirt production. The toxic releases from washing and disposal in the life cycle of T-shirts appear to be of minor relevance. By contrast, the production phase may be rather significant due to toxic silver emissions at the mining site if high silver quantities are require