Psychiatric disorders are a common prognostic marker for worse outcome in patients with idiopathic intracranial hypertension

Objective: Idiopathic intracranial hypertension (IIH) is aetiologically unknown disorder that associates with endocrinological disturbances, including dysfunction of hypothalamic-pituitary-adrenal-axis. Neuroendocrinological dysfunctions have also been characterized in psychiatric disorders, and therefore we investigated the presence of psychiatric disorders of patients with IIH in a well-defined cohort.Patients and methods: A total of 51 patients with IIH were included. Patient demographics, symptoms, imaging data, ophthalmological and clinical findings were collected.Results: At the time of diagnosis the mean age was 32.5years (SD 10.7), the body mass index was 37.1 kg/m(2) (SD 7.4), and the opening pressure 29.1 mmHg (SD 6.2). A total of 88.2% of patients were female and 45.1% were diagnosed with a psychiatric co-morbidity prior to IIH diagnosis. The mean follow-up time was 4.4 years (SD 5.4). The overall treatment outcome was significantly poorer on a group of patients with psychiatric diagnosis when compared to individuals without such history (p = 0.001), but there were no differences in the resolution of papilledema (p = 0.405). Patients with IIH and psychiatric disorders had more often empty sella on their imaging at diagnosis when compared to patients without psychiatric co-morbidity (p = 0.044).Conclusion: Psychiatric disorders are highly prevalent in patients with IIH and associate with worse subjective outcomes. These findings advocate for monitoring the mental health of patients with IIH and warrant further multidisciplinary research to understand the potentially underlying psychosocial and neuroendocrinological mechanisms

Broad-Spectrum Antiviral Activity of RNA Interference against Four Genotypes of Japanese Encephalitis Virus Based on Single MicroRNA Polycistrons

Japanese encephalitis virus (JEV), a neurotropic mosquito-borne flavivirus, causes acute viral encephalitis and neurologic disease with a high fatality rate in humans and a range of animals. Small interfering RNA (siRNA) is a powerful antiviral agent able to inhibit JEV replication. However, the high rate of genetic variability between JEV strains (of four confirmed genotypes, genotypes I, II, III and IV) hampers the broad-spectrum application of siRNAs, and mutations within the targeted sequences could facilitate JEV escape from RNA interference (RNAi)-mediated antiviral therapy. To improve the broad-spectrum application of siRNAs and prevent the generation of escape mutants, multiple siRNAs targeting conserved viral sequences need to be combined. In this study, using a siRNA expression vector based on the miR-155 backbone and promoted by RNA polymerase II, we initially identified nine siRNAs targeting highly conserved regions of seven JEV genes among strains of the four genotypes of JEV to effectively block the replication of the JEV vaccine strain SA14-14-2. Then, we constructed single microRNA-like polycistrons to simultaneously express these effective siRNAs under a single RNA polymerase II promoter. Finally, these single siRNAs or multiple siRNAs from the microRNA-like polycistrons showed effective anti-virus activity in genotype I and genotype III JEV wild type strains, which are the predominant genotypes of JEV in mainland China. The anti-JEV effect of these microRNA-like polycistrons was also predicted in other genotypes of JEV (genotypes II and IV), The inhibitory efficacy indicated that siRNAs×9 could theoretically inhibit the replication of JEV genotypes II and IV

A Non Membrane-Targeted Human Soluble CD59 Attenuates Choroidal Neovascularization in a Model of Age Related Macular Degeneration

Age related macular degeneration (AMD) is the most common cause of blindness amongst the elderly. Approximately 10% of AMD patients suffer from an advanced form of AMD characterized by choroidal neovascularization (CNV). Recent evidence implicates a significant role for complement in the pathogenesis of AMD. Activation of complement terminates in the incorporation of the membrane attack complex (MAC) in biological membranes and subsequent cell lysis. Elevated levels of MAC have been documented on choroidal blood vessels and retinal pigment epithelium (RPE) of AMD patients. CD59 is a naturally occurring membrane bound inhibitor of MAC formation. Previously we have shown that membrane bound human CD59 delivered to the RPE cells of mice via an adenovirus vector can protect those cells from human complement mediated lysis ex vivo. However, application of those observations to choroidal blood vessels are limited because protection from MAC- mediated lysis was restricted only to the cells originally transduced by the vector. Here we demonstrate that subretinal delivery of an adenovirus vector expressing a transgene for a soluble non-membrane binding form of human CD59 can attenuate the formation of laser-induced choroidal neovascularization and murine MAC formation in mice even when the region of vector delivery is distal to the site of laser induced CNV. Furthermore, this same recombinant transgene delivered to the intravitreal space of mice by an adeno-associated virus vector (AAV) can also attenuate laser-induced CNV. To our knowledge, this is the first demonstration of a non-membrane targeting CD59 having biological potency in any animal model of disease in vivo. We propose that the above approaches warrant further exploration as potential approaches for alleviating complement mediated damage to ocular tissues in AMD

Exploiting Ligand-Protein Conjugates to Monitor Ligand-Receptor Interactions

We introduce three assays for analyzing ligand-receptor interactions based on the specific conjugation of ligands to SNAP-tag fusion proteins. Conjugation of ligands to different SNAP-tag fusions permits the validation of suspected interactions in cell extracts and fixed cells as well as the establishment of high-throughput assays. The different assays allow the analysis of strong and weak interactions. Conversion of ligands into SNAP-tag substrates thus provides access to a powerful toolbox for the analysis of their interactions with proteins

Atomic Layer Deposition (ALD) to Mitigate Tin Whisker Growth and Corrosion Issues on Printed Circuit Board Assemblies

This paper presents the results of a research program set up to evaluate atomic layer deposition (ALD) conformal coatings as a method of mitigating the growth of tin whiskers from printed circuit board assemblies. The effect of ALD coating process variables on the ability of the coating to mitigate whisker growth were evaluated. Scanning electron microscopy and optical microscopy were used to evaluate both the size and distribution of tin whiskers and the coating/whisker interactions. Results show that the ALD process can achieve significant reductions in whisker growth and thus offers considerable potential as a reworkable whisker mitigation strategy. The effect of ALD layer thickness on whisker formation was also investigated. Studies indicate that thermal exposure during ALD processing may contribute significantly to the observed whisker mitigation

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal