TREATMENT WITH TAMSULOSIN IN PATIENTS WITH DISTAL URETERAL CALCULI

Background: Symptomatic ureteral calculi are one of the most important issues in urologist emergency clinical settings. Spontaneous passage of distal ureteral calculi is usually achieved with good hydration and spasmoanalgetic drugs. alpha-blocker therapy may facilitate and accelerate the spontaneous passage of ureteral stones.Patients and methodsIn retrospective study we analyzed patients with renal colic admitted to our department in 2006. All of them had clinical examination, urine and blood analysis, plain radiography (number, size and location of radiopaque calculi) and intravenous pyelography (kidney function and morphology). All patients with distal ureteral calcus were treated with spasmoanalgetics and with or without alpha-adrenergic antagonist tamsulosin. We analyzed eventual spontaneous passage of the calculi, additional procedures (splints, ureterorenoscopy, open procedures, extracorporeal shock wave lithotripsy (ESWL)). We used Student's t-test for statistical analysis.Results48 from 72 patients had urinary calculus. 35 (73 %) of them had calculus in the distal part of ureter. 17 (49 %) of 35 patients with distal ureteral calculus were treated with tamsulosin and in all (100 %) spontaneous stone passage was observed. 18 (51 %) patients were not treated with tamsulosin and spontaneous passage was observed in 18 (65 %) patients (p = 0.000).ConclusionsTamsulosin therapy promotes expulsion of ureteral stones

Antiferromagnetic fluctuations in the normal state of LiFeAs

We present a detailed study of 75As NMR Knight shift and spin-lattice relaxation rate in the normal state of stoichiometric polycrystalline LiFeAs. Our analysis of the Korringa relation suggests that LiFeAs exhibits strong antiferromagnetic fluctuations, if transferred hyperfine coupling is a dominant interaction between 75As nuclei and Fe electronic spins, whereas for an on-site hyperfine coupling scenario, these are weaker, but still present to account for our experimental observations. Density-functional calculations of electric field gradient correctly reproduce the experimental values for both 75As and 7Li sites.Comment: 5 pages, 3 figures, thoroughly revised version with refined experimental data, accepted for publication as a Rapid Communication in Physical Review B

Longitudinal DNA methylation changes at MET may alter HGF/c-MET signalling in adolescents at risk for depression

Unrecognized depression during adolescence can result in adult suicidal behaviour. The aim of this study was to identify, replicate and characterize DNA methylation (DNAm) shifts in depression aetiology, using a longitudinal, multi-tissue (blood and brain) and multi-layered (genetics, epigenetics, transcriptomics) approach. We measured genome-wide blood DNAm data at baseline and one-year follow-up, and imputed genetic variants, in 59 healthy adolescents comprising the discovery cohort. Depression and suicidal symptoms were determined using the Development and Well-Being Assessment (DAWBA) depression band, Montgomery-Åsberg Depression Rating Scale-Self (MADRS-S) and SUicide Assessment Scale (SUAS). DNAm levels at follow-up were regressed against depression scores, adjusting for sex, age and the DNAm residuals at baseline. Higher methylation levels of 5% and 13% at cg24627299 within the MET gene were associated with higher depression scores (praw<1e-4) and susceptibility for suicidal symptoms (padj.<0.005). The nearby rs39748 was discovered to be a methylation and expression quantitative trait locus in blood cells. mRNA levels of hepatocyte growth factor (HGF) expression, known to strongly interact with MET, were inversely associated with methylation levels at cg24627299, in an independent cohort of 1180 CD14+ samples. In an open-access dataset of brain tissue, lower methylation at cg24627299 was found in 45 adults diagnosed with major depressive disorder compared with matched controls (padj.<0.05). Furthermore, lower MET expression was identified in the hippocampus of depressed individuals compared with controls in a fourth, independent cohort. Our findings reveal methylation changes at MET in the pathology of depression, possibly involved in downregulation of HGF/c-MET signalling the hippocampal region

Spin amplitude modulation driven magnetoelectic coupling in the new multiferroic FeTe2_2O5_5Br

Magnetic and ferroelectric properties of layered geometrically frustrated cluster compound FeTe$_2$O$_5$Br were investigated with single-crystal neutron diffraction and dielectric measurements. Incommensurate amplitude modulated magnetic order with the wave vector $\bf{q}$=(\half, 0.463, 0) develops below $T_N=10.6(2) {\rm K}$. Simultaneously, a ferroelectric order with the spontaneous polarization perpendicular to ${\bf q}$ and to Fe$^{3+}$ magnetic moments emerges. The observed ferroelectricity and extraordinary linear scaling of the ferroelectric and magnetic order parameter are provoked by the striction of the intercluster Fe-O-Te-O-Fe bridges leading to the shift of Te$^{4+}$ ions and polarization of their lone-pair electrons

Fine-Mapping Resolves Eae23 into Two QTLs and Implicates ZEB1 as a Candidate Gene Regulating Experimental Neuroinflammation in Rat

This study was supported by grants from the Swedish Research Council, The Wadsworth Foundation, Söderbergs Foundation, Petrus and Augusta Hedlunds Foundation, Bibbi and Niels Jensens Foundation, Montel Williams Foundation, Åke-Wibergs Stiftelse, the Swedish Foundation for Neurologically Disabled and the EU 6TH Framework EURATools (LSHG-CT-2005-019015) and Neuropromise (LSHM-CT-2005-018637)

Small noncoding RNA profiling across cellular and biofluid compartments and their implications for multiple sclerosis immunopathology

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease affecting the central nervous system (CNS). Small non-coding RNAs (sncRNAs) and, in particular, microRNAs (miRNAs) have frequently been associated with MS. Here, we performed a comprehensive analysis of all classes of sncRNAs in matching samples of peripheral blood mononuclear cells (PBMCs), plasma, cerebrospinal fluid (CSF) cells, and cell-free CSF from relapsing-remitting (RRMS, n = 12 in relapse and n = 11 in remission) patients, secondary progressive (SPMS, n = 6) MS patients, and noninflammatory and inflammatory neurological disease controls (NINDC, n = 11; INDC, n = 5). We show widespread changes in miRNAs and sncRNA-derived fragments of small nuclear, nucleolar, and transfer RNAs. In CSF cells, 133 out of 133 and 115 out of 117 differentially expressed sncRNAs were increased in RRMS relapse compared to remission and RRMS compared to NINDC, respectively. In contrast, 65 out of 67 differentially expressed PBMC sncRNAs were decreased in RRMS compared to NINDC. The striking contrast between the periphery and CNS suggests that sncRNA-mediated mechanisms, including alternative splicing, RNA degradation, and mRNA translation, regulate the transcriptome of pathogenic cells primarily in the CNS target organ.Peer reviewe

An evaluation of analysis pipelines for DNA methylation profiling using the Illumina HumanMethylation450 BeadChip platform

The proper identification of differentially methylated CpGs is central in most epigenetic studies. The Illumina HumanMethylation450 BeadChip is widely used to quantify DNA methylation; nevertheless, the design of an appropriate analysis pipeline faces severe challenges due to the convolution of biological and technical variability and the presence of a signal bias between Infinium I and II probe design types. Despite recent attempts to investigate how to analyze DNA methylation data with such an array design, it has not been possible to perform a comprehensive comparison between different bioinformatics pipelines due to the lack of appropriate data sets having both large sample size and sufficient number of technical replicates. Here we perform such a comparative analysis, targeting the problems of reducing the technical variability, eliminating the probe design bias and reducing the batch effect by exploiting two unpublished data sets, which included technical replicates and were profiled for DNA methylation either on peripheral blood, monocytes or muscle biopsies. We evaluated the performance of different analysis pipelines and demonstrated that: (1) it is critical to correct for the probe design type, since the amplitude of the measured methylation change depends on the underlying chemistry; (2) the effect of different normalization schemes is mixed, and the most effective method in our hands were quantile normalization and Beta Mixture Quantile dilation (BMIQ); (3) it is beneficial to correct for batch effects. In conclusion, our comparative analysis using a comprehensive data set suggests an efficient pipeline for proper identification of differentially methylated CpGs using the Illumina 450K arrays

Neuronal methylome reveals CREB-associated neuro-axonal impairment in multiple sclerosis

BACKGROUND: Due to limited access to brain tissue, the precise mechanisms underlying neuro-axonal dysfunction in neurological disorders such as multiple sclerosis (MS) are largely unknown. In that context, profiling DNA methylation, which is a stable and cell type-specific regulatory epigenetic mark of genome activity, offers a unique opportunity to characterize the molecular mechanisms underpinning brain pathology in situ. We examined DNA methylation patterns of neuronal nuclei isolated from post-mortem brain tissue to infer processes that occur in neurons of MS patients. RESULTS: We isolated subcortical neuronal nuclei from post-mortem white matter tissue of MS patients and non-neurological controls using flow cytometry. We examined bulk DNA methylation changes (total n = 29) and further disentangled true DNA methylation (5mC) from neuron-specific DNA hydroxymethylation (5hmC) (n = 17), using Illumina Infinium 450K arrays. We performed neuronal sub-type deconvolution using glutamate and GABA methylation profiles to further reduce neuronal sample heterogeneity. In total, we identified 2811 and 1534 significant (genome-wide adjusted P value < 0.05) differentially methylated and hydroxymethylated positions between MS patients and controls. We found striking hypo-5mC and hyper-5hmC changes occurring mainly within gene bodies, which correlated with reduced transcriptional activity, assessed using published RNAseq data from bulk brain tissue of MS patients and controls. Pathway analyses of the two cohorts implicated dysregulation of genes involved in axonal guidance and synaptic plasticity, with meta-analysis confirming CREB signalling as the most highly enriched pathway underlying these processes. We functionally investigated DNA methylation changes of CREB signalling-related genes by immunohistofluoresence of phosphorylated CREB in neurons from brain sections of a subcohort of MS patients and controls (n = 15). Notably, DNA methylation changes associated with a reduction of CREB activity in white matter neurons of MS patients compared to controls. CONCLUSIONS: Our data demonstrate that investigating 5mC and 5hmC modifications separately allows the discovery of a substantial fraction of changes occurring in neurons, which can escape traditional bisulfite-based DNA methylation analysis. Collectively, our findings indicate that neurons of MS patients acquire sustained hypo-5mC and hyper-5hmC, which may impair CREB-mediated neuro-axonal integrity, in turn relating to clinical symptoms