Microcytosis and possible early iron deficiency in paediatric inpatients: a retrospective audit.

BACKGROUND: Iron deficiency anaemia is a common paediatric problem worldwide, with significant neurodevelopmental morbidity if left untreated. A decrease in the mean corpuscular volume (MCV) can be used as a surrogate marker for detecting early iron deficiency prior to definitive investigation and treatment. An audit cycle was therefore undertaken to evaluate and improve the identification, follow-up and treatment of abnormally low MCV results amongst the paediatric inpatients in an English district general hospital. METHODS: The audit cycle was performed retrospectively over two three-month periods (February to April 2006; September to November 2006), amongst patients aged between one month and 16 years that had full blood counts performed whilst admitted on the paediatric ward. Patients with at least one abnormally low MCV result were identified, and their notes reviewed. We looked for any underlying explanation for the result, adequate documentation of the result as abnormal, and instigation of follow-up or treatment. In-between the two audit periods, the results of the first audit period were presented to the medical staff and suggestions were made for improvements in documentation and follow-up of abnormal results. The z-test was used to test for equality of proportions between the two audit samples. RESULTS: Out of 701 inpatients across both audit periods that had full blood counts, 61 (8.7%) had a low MCV result. Only 15% of patients in each audit period had an identifiable explanation for their low MCV values. Amongst the remaining 85% with either potentially explicable or inexplicable results, there was a significant increase in documentation of results as abnormal from 25% to 91% of cases between the first and second audit periods (p = 0.00 using z-test). However, there was no accompanying increase in the proportion of patients who received follow-up or treatment for their abnormal results. CONCLUSION: Abnormal red cell indices that may indicate iron deficiency are frequently missed amongst paediatric inpatients. Medical staff education and the use of appropriate protocols or pathways could further improve detection and treatment rates in this setting

Free-breathing myocardial T2* mapping using GRE-EPI and automatic non-rigid motion correction

BACKGROUND: Measurement of myocardial T2* is becoming widely used in the assessment of patients at risk for cardiac iron overload. The conventional breath-hold, ECG-triggered, segmented, multi-echo gradient echo (MGRE) sequence used for myocardial T2* quantification is very sensitive to respiratory motion and may not be feasible in patients who are unable to breath-hold. We propose a free-breathing myocardial T2* mapping approach that combines a single-shot gradient-echo echo-planar imaging (GRE-EPI) sequence for T2*-weighted image acquisition with automatic non-rigid motion correction (MOCO) of respiratory motion between single-shot images. METHODS: ECG-triggered T2*-weighted images at different echo times were acquired by a black-blood, single-shot GRE-EPI sequence during free-breathing. A single image at a single TE is acquired in each heartbeat. Automatic non-rigid MOCO was applied to correct for in-plane respiratory motion before pixel-wise T2* mapping. In a total of 117 patients referred for clinical cardiac magnetic resonance exams, the free-breathing MOCO GRE-EPI sequence was compared to the breath-hold segmented MGRE approach. Image quality was scored independently by 2 experienced observers blinded to the particular image acquisition strategy. T2* measurements in the interventricular septum and in the liver were compared for the two methods in all cases with adequate image quality. RESULTS: T2* maps were acquired in all 117 patients using the breath-hold MGRE and the free-breathing MOCO GRE-EPI approaches, including 8 patients with myocardial iron overload and 25 patients with hepatic iron overload. The mean image quality of the free-breathing MOCO GRE-EPI images was scored significantly higher than that of the breath-hold MGRE images by both reviewers. Out of the 117 studies, 21 breath-hold MGRE studies (17.9 % of all the patients) were scored to be less than adequate or very poor by both reviewers, while only 2 free-breathing MOCO GRE-EPI studies were scored to be less than adequate image quality. In a comparative evaluation of the images with at least adequate quality, the intra-class correlation coefficients for myocardial and liver T2* were 0.868 and 0.986 respectively (p < 0.001), indicating that the T2* measured by breath-hold MGRE and free-breathing MOCO GRE-EPI were in close agreement. The coefficient of variation between the breath-hold and free-breathing approaches for myocardial and liver T2* were 9.88 % and 9.38 % respectively. Bland-Altman plots demonstrated good absolute agreement of T2* in the interventricular septum and the liver from the free-breathing and breath-hold approaches (mean differences -0.03 and 0.16 ms, respectively). CONCLUSION: The free-breathing approach described for T2* mapping using MOCO GRE-EPI enables accurate myocardial and liver T2* measurements and is insensitive to respiratory motion

Semi-analytical approach to magnetized temperature autocorrelations

The cosmic microwave background (CMB) temperature autocorrelations, induced by a magnetized adiabatic mode of curvature inhomogeneities, are computed with semi-analytical methods. As suggested by the latest CMB data, a nearly scale-invariant spectrum for the adiabatic mode is consistently assumed. In this situation, the effects of a fully inhomogeneous magnetic field are scrutinized and constrained with particular attention to harmonics which are relevant for the region of Doppler oscillations. Depending on the parameters of the stochastic magnetic field a hump may replace the second peak of the angular power spectrum. Detectable effects on the Doppler region are then expected only if the magnetic power spectra have quasi-flat slopes and typical amplitude (smoothed over a comoving scale of Mpc size and redshifted to the epoch of gravitational collapse of the protogalaxy) exceeding 0.1 nG. If the magnetic energy spectra are bluer (i.e. steeper in frequency) the allowed value of the smoothed amplitude becomes, comparatively, larger (in the range of 20 nG). The implications of this investigation for the origin of large-scale magnetic fields in the Universe are discussed. Connections with forthcoming experimental observations of CMB temperature fluctuations are also suggested and partially explored.Comment: 40 pages, 13 figure

Post-Transcriptional Regulation of BCL2 mRNA by the RNA-Binding Protein ZFP36L1 in Malignant B Cells

The human ZFP36 zinc finger protein family consists of ZFP36, ZFP36L1, and ZFP36L2. These proteins regulate various cellular processes, including cell apoptosis, by binding to adenine uridine rich elements in the 3′ untranslated regions of sets of target mRNAs to promote their degradation. The pro-apoptotic and other functions of ZFP36 family members have been implicated in the pathogenesis of lymphoid malignancies. To identify candidate mRNAs that are targeted in the pro-apoptotic response by ZFP36L1, we reverse-engineered a gene regulatory network for all three ZFP36 family members using the ‘maximum information coefficient’ (MIC) for target gene inference on a large microarray gene expression dataset representing cells of diverse histological origin. Of the three inferred ZFP36L1 mRNA targets that were identified, we focussed on experimental validation of mRNA for the pro-survival protein, BCL2, as a target for ZFP36L1. RNA electrophoretic mobility shift assay experiments revealed that ZFP36L1 interacted with the BCL2 adenine uridine rich element. In murine BCL1 leukemia cells stably transduced with a ZFP36L1 ShRNA lentiviral construct, BCL2 mRNA degradation was significantly delayed compared to control lentiviral expressing cells and ZFP36L1 knockdown in different cell types (BCL1, ACHN, Ramos), resulted in increased levels of BCL2 mRNA levels compared to control cells. 3′ untranslated region luciferase reporter assays in HEK293T cells showed that wild type but not zinc finger mutant ZFP36L1 protein was able to downregulate a BCL2 construct containing the BCL2 adenine uridine rich element and removal of the adenine uridine rich core from the BCL2 3′ untranslated region in the reporter construct significantly reduced the ability of ZFP36L1 to mediate this effect. Taken together, our data are consistent with ZFP36L1 interacting with and mediating degradation of BCL2 mRNA as an important target through which ZFP36L1 mediates its pro-apoptotic effects in malignant B-cells

Eukaryotic Cells Producing Ribosomes Deficient in Rpl1 Are Hypersensitive to Defects in the Ubiquitin-Proteasome System

It has recently become clear that the misassembly of ribosomes in eukaryotic cells can have deleterious effects that go far beyond a simple shortage of ribosomes. In this work we find that cells deficient in ribosomal protein L1 (Rpl1; Rpl10a in mammals) produce ribosomes lacking Rpl1 that are exported to the cytoplasm and that can be incorporated into polyribosomes. The presence of such defective ribosomes leads to slow growth and appears to render the cells hypersensitive to lesions in the ubiquitin-proteasome system. Several genes that were reasonable candidates for degradation of 60S subunits lacking Rpl1 fail to do so, suggesting that key players in the surveillance of ribosomal subunits remain to be found. Interestingly, in spite of rendering the cells hypersensitive to the proteasome inhibitor MG132, shortage of Rpl1 partially suppresses the stress-invoked temporary repression of ribosome synthesis caused by MG132.United States. National Institutes of Health (GM25532)United States. National Institutes of Health (ARRAGM25532-S1)United States. National Institutes of Health (GM085177)United States. National Institutes of Health (CAI-3330)Natural Sciences and Engineering Research Council of Canada (NSERC

Ευρετικές προσεγγίσεις του μοναδιάστατου προβλήματος πακετοποίησης

Article 59.1, of the International Code of Nomenclature for Algae, Fungi, and Plants (ICN; Melbourne Code), which addresses the nomenclature of pleomorphic fungi, became effective from 30 July 2011. Since that date, each fungal species can have one nomenclaturally correct name in a particular classification. All other previously used names for this species will be considered as synonyms. The older generic epithet takes priority over the younger name. Any widely used younger names proposed for use, must comply with Art. 57.2 and their usage should be approved by the Nomenclature Committee for Fungi (NCF). In this paper, we list all genera currently accepted by us in Dothideomycetes (belonging to 23 orders and 110 families), including pleomorphic and non-pleomorphic genera. In the case of pleomorphic genera, we follow the rulings of the current ICN and propose single generic names for future usage. The taxonomic placements of 1261 genera are listed as an outline. Protected names and suppressed names for 34 pleomorphic genera are listed separately. Notes and justifications are provided for possible proposed names after the list of genera. Notes are also provided on recent advances in our understanding of asexual and sexual morph linkages in Dothideomycetes. A phylogenetic tree based on four gene analyses supported 23 orders and 75 families, while 35 families still lack molecular data

How patients understand depression associated with chronic physical disease - A systematic review

Background: Clinicians are encouraged to screen people with chronic physical illness for depression. Screening alone may not improve outcomes, especially if the process is incompatible with patient beliefs. The aim of this research is to understand peoples beliefs about depression, particularly in the presence of chronic physical disease. Methods: A mixed method systematic review involving a thematic analysis of qualitative studies and quantitative studies of beliefs held by people with current depressive symptoms. MEDLINE, EMBASE, PSYCHINFO, CINAHL, BIOSIS, Web of Science, The Cochrane Library, UKCRN portfolio, National Research Register Archive, Clinicaltrials.gov and OpenSIGLE were searched from database inception to 31st December 2010. A narrative synthesis of qualitative and quantitative data, based initially upon illness representations and extended to include other themes not compatible with that framework. Results: A range of clinically relevant beliefs was identified from 65 studies including the difficulty in labeling depression, complex causal factors instead of the biological model, the roles of different treatments and negative views about the consequences of depression. We found other important themes less related to ideas about illness: the existence of a self-sustaining depression spiral; depression as an existential state; the ambiguous status of suicidal thinking; and the role of stigma and blame in depression. Conclusions: Approaches to detection of depression in physical illness need to be receptive to the range of beliefs held by patients. Patient beliefs have implications for engagement with depression screening

RNA-Seq transcriptomics and pathway analyses reveal potential regulatory genes and molecular mechanisms in high- and low-residual feed intake in Nordic dairy cattle

BACKGROUND: The selective breeding of cattle with high-feed efficiencies (FE) is an important goal of beef and dairy cattle producers. Global gene expression patterns in relevant tissues can be used to study the functions of genes that are potentially involved in regulating FE. In the present study, high-throughput RNA sequencing data of liver biopsies from 19 dairy cows were used to identify differentially expressed genes (DEGs) between high- and low-FE groups of cows (based on Residual Feed Intake or RFI). Subsequently, a profile of the pathways connecting the DEGs to FE was generated, and a list of candidate genes and biomarkers was derived for their potential inclusion in breeding programmes to improve FE. RESULTS: The bovine RNA-Seq gene expression data from the liver was analysed to identify DEGs and, subsequently, identify the molecular mechanisms, pathways and possible candidate biomarkers of feed efficiency. On average, 57 million reads (short reads or short mRNA sequences < ~200 bases) were sequenced, 52 million reads were mapped, and 24,616 known transcripts were quantified according to the bovine reference genome. A comparison of the high- and low-RFI groups revealed 70 and 19 significantly DEGs in Holstein and Jersey cows, respectively. The interaction analysis (high vs. low RFI x control vs. high concentrate diet) showed no interaction effects in the Holstein cows, while two genes showed interaction effects in the Jersey cows. The analyses showed that DEGs act through certain pathways to affect or regulate FE, including steroid hormone biosynthesis, retinol metabolism, starch and sucrose metabolism, ether lipid metabolism, arachidonic acid metabolism and drug metabolism cytochrome P450. CONCLUSION: We used RNA-Seq-based liver transcriptomic profiling of high- and low-RFI dairy cows in two breeds and identified significantly DEGs, their molecular mechanisms, their interactions with other genes and functional enrichments of different molecular pathways. The DEGs that were identified were the CYP’s and GIMAP genes for the Holstein and Jersey cows, respectively, which are related to the primary immunodeficiency pathway and play a major role in feed utilization and the metabolism of lipids, sugars and proteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-017-3622-9) contains supplementary material, which is available to authorized users

Investigation of Polyurea-Crosslinked Silica Aerogels as a Neuronal Scaffold: A Pilot Study

BACKGROUND: Polymer crosslinked aerogels are an attractive class of materials for future implant applications particularly as a biomaterial for the support of nerve growth. The low density and nano-porous structure of this material combined with large surface area, high mechanical strength, and tunable surface properties, make aerogels materials with a high potential in aiding repair of injuries of the peripheral nervous system. however, the interaction of neurons with aerogels remains to be investigated. METHODOLOGY: In this work the attachment and growth of neurons on clear polyurea crosslinked silica aerogels (PCSA) coated with: poly-L-lysine, basement membrane extract (BME), and laminin1 was investigated by means of optical and scanning electron microscopy. After comparing the attachment and growth capability of neurons on these different coatings, laminin1 and BME were chosen for nerve cell attachment and growth on PCSA surfaces. The behavior of neurons on treated petri dish surfaces was used as the control and behavior of neurons on treated PCSA discs was compared against it. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that: 1) untreated PCSA surfaces do not support attachment and growth of nerve cells, 2) a thin application of laminin1 layer onto the PCSA discs adhered well to the PCSA surface while also supporting growth and differentiation of neurons as evidenced by the number of processes extended and b3-tubulin expression, 3) three dimensional porous structure of PCSA remains intact after fixing protocols necessary for preservation of biological samples and 4) laminin1 coating proved to be the most effective method for attaching neurons to the desired regions on PCSA discs. This work provides the basis for potential use of PCSA as a biomaterial scaffold for neural regeneration

Gene expression profiling of gliomas: merging genomic and histopathological classification for personalised therapy

The development of DNA microarray technologies over the past decade has revolutionised translational cancer research. These technologies were originally hailed as more objective, comprehensive replacements for traditional histopathological cancer classification systems, based on microscopic morphology. Although DNA microarray-based gene expression profiling (GEP) remains unlikely in the near term to completely replace morphological classification of primary brain tumours, specifically the diffuse gliomas, GEP has confirmed that significant molecular heterogeneity exists within the various morphologically defined gliomas, particularly glioblastoma (GBM). Herein, we provide a 10-year progress report on human glioma GEP, with focus on development of clinical diagnostic tests to identify molecular subtypes, uniquely responsive to adjuvant therapies. Such progress may lead to a more precise classification system that accurately reflects the cellular, genetic, and molecular basis of gliomagenesis, a prerequisite for identifying subsets uniquely responsive to specific adjuvant therapies, and ultimately in achieving individualised clinical care of glioma patients