Functional improvement and correlations with symptomatic improvement in adults with attention deficit hyperactivity disorder receiving long-acting methylphenidate

Item does not contain fulltextBACKGROUND: Data on the relationship between core symptoms and daily functioning in adults with attention deficit hyperactivity disorder (ADHD) are limited. Daily functioning was assessed as part of an open-label extension, and associations with symptom scores were evaluated. METHOD: After a 5-week double-blind study with adults with ADHD receiving osmotic-controlled release oral delivery system (OROS) methylphenidate (MPH) 18, 36 or 72 mg/day, or placebo, participants were eligible for a 7-week open-label extension in which all patients received OROS MPH. Data for the Conners' Adult ADHD Rating Scale - Observer: Screening Version (CAARS-O:SV) (primary endpoint) have been presented previously. Secondary endpoints included the observer self-reported short version of the CAARS (CAARS-S:S) and the Clinical Global Impressions - Severity Scale (CGI-S). Daily functioning and quality of life were assessed using the Sheehan Disability Scale (SDS) and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) respectively. In post-hoc analyses, changes in CAARS-O:SV were evaluated in subgroups. Relationships between symptom and functional outcomes were evaluated in a multivariate regression analysis. RESULTS: A total of 370 patients entered the open-label extension. Significant improvements from baseline in CAARS-O:SV were similar regardless of sex, ADHD subtype, prior treatment or psychiatric co-morbidity. Significant improvements from double-blind baseline were also seen for the CAARS-S:S, CGI-S, SDS and Q-LES-Q. Improvements in the CAARS-O:SV Hyperactivity/Impulsivity subscale were associated with improvements in SDS total and subscale scores, and in the Q-LES-Q score at open-label endpoint. Improvements in CAARS-O:SV Inattention subscale and CGI-S scores were not significantly associated with functional changes. CONCLUSIONS: Improvements in ADHD symptoms relating to hyperactivity and impulsivity in adults receiving OROS MPH are associated with improvements in daily functioning and quality of life.1 januari 201

Loss of the mammal-specific tectorial membrane component CEA cell adhesion molecule 16 (CEACAM16) leads to hearing impairment at low and high frequencies

The vertebrate-restricted carcinoembryonic antigen gene family evolves extremely rapidly. Among their widely expressed members, the mammal-specific, secreted CEACAM16 is exceptionally well conserved and specifically expressed in the inner ear. To elucidate a potential auditory function we inactivated murine Ceacam16 by homologous recombination. In young Ceacam16-/- mice the hearing threshold for frequencies below 10 kHz and above 22 kHz was raised. This hearing impairment progressed with age. A similar phenotype is observed in hearing-impaired members of Family 1070 with non-syndromic autosomal dominant hearing loss (DFNA4) who carry a missense mutation in CEACAM16. CEACAM16 was found in interdental and Deiters cells and was deposited in the tectorial membrane of the cochlea between postnatal day 12 and 15, when hearing starts in mice. In cochlear sections of Ceacam16-/- mice tectorial membranes were significantly more often stretched out as compared to wild-type mice where they were mostly contracted and detached from the outer hair cells. Homotypic cell sorting observed after ectopic cell surface expression of the carboxy-terminal immunoglobulin variable-like N2 domain of CEACAM16 indicated that CEACAM16 can interact in trans. Furthermore, Western blot analyses of membrane-bound CEACAM16 under reducing and non-reducing conditions demonstrated oligomerization via unpaired cysteines. Taken together, CEACAM16 probably can form higher order structures with other tectorial membrane proteins such as α-tectorin and β-tectorin and influences the physical properties of the tectorial membrane. Evolution of CEACAM16 might have been an important step for the specialization of the mammalian cochlea allowing hearing over an extended frequency range

In-situ observations of young contrails – overview and selected results from the CONCERT campaign

Lineshaped contrails were detected with the research aircraft Falcon during the CONCERT – CONtrail and Cirrus ExpeRimenT – campaign in October/November 2008. The Falcon was equipped with a set of instruments to measure the particle size distribution, shape, extinction and chemical composition as well as trace gas mixing ratios of sulfur dioxide (SO<sub>2</sub>), reactive nitrogen and halogen species (NO, NO<sub>y</sub>, HNO<sub>3</sub>, HONO, HCl), ozone (O<sub>3</sub>) and carbon monoxide (CO). During 12 mission flights over Europe, numerous contrails, cirrus clouds and a volcanic aerosol layer were probed at altitudes between 8.5 and 11.6 km and at temperatures above 213 K. 22 contrails from 11 different aircraft were observed near and below ice saturation. The observed NO mixing ratios, ice crystal and soot number densities are compared to a process based contrail model. On 19 November 2008 the contrail from a CRJ-2 aircraft was penetrated in 10.1 km altitude at a temperature of 221 K. The contrail had mean ice crystal number densities of 125 cm<sup>−3</sup> with effective radii <i>r</i><sub>eff</sub> of 2.6 μm. The presence of particles with <i>r</i>>50 μm in the less than 2 min old contrail suggests that natural cirrus crystals were entrained in the contrail. Mean HONO/NO (HONO/NO<sub>y</sub>) ratios of 0.037 (0.024) and the fuel sulfur conversion efficiency to H<sub>2</sub>SO<sub>4</sub> (ε<sub><i>S</i>↓</sub>) of 2.9 % observed in the CRJ-2 contrail are in the range of previous measurements in the gaseous aircraft exhaust. On 31 October 2010 aviation NO emissions could have contributed by more than 40% to the regional scale NO levels in the mid-latitude lowest stratosphere. The CONCERT observations help to better quantify the climate impact from contrails and will be used to investigate the chemical processing of trace gases on contrails

Beyond ‘geo-economics’: advanced unevenness and the anatomy of German austerity

This article aims to shed new light on Germany’s domineering role in the eurocrisis. I argue that the realist-inspired depiction of Germany as a ‘geo-economic power’, locked into zero-sum competition with its European partners, is built around an empty core: unable to theorise how anarchy shapes the calculus of states where security competition has receded, it cannot explain why German state managers have insisted on an austerity response to the crisis despite its significant risks and costs even for Germany itself. To unlock this puzzle, this article outlines a version of uneven and combined development (UCD) that is better able to capture the international pressures and opportunities faced by policy elites in advanced capitalist states that no longer encounter one another as direct security rivals. Applied to Germany, this lens reveals a twofold unevenness in the historical structures and growth cycles of capitalist economies that shape its contradictory choice for austerity. In the long run, the reorientation of the export-dependent German economy from Europe towards Asian and Latin American late industrialisers renders the structural adjustment of the eurozone an opportunity—from the cost-saving view of German manufacturers producing in the European home market for export abroad, as well as for German state officials keen to sustain a crumbling class compromise centred on Germany’s world market success. In the short term, however, its exposed position between the divergent post-crisis trajectories of the US and Europe accelerates pressures for austerity beyond what German state and corporate elites would otherwise consider feasible

Association between anxiety and non-coding genetic variants of the galanin neuropeptide

Galanin, an inhibitory neuropeptide and cotransmitter has long been known to co-localize with noradrenaline and serotonin in the central nervous system. Several human studies demonstrated altered galanin expression levels in major depressive disorder and anxiety. Pharmacological modulation of galanin signaling and transgenic strategies provide further proof for the involvement of the galanin system in the pathophysiology of mood disorders. Little is known, however, on the dynamic regulation of galanin expression at the transcriptional level. The aim of the present study was to seek genetic association of non-coding single nucleotide variations in the galanin gene with anxiety and depression.Six single nucleotide polymorphisms (SNP) occurring either in the regulatory 5' or 3' flanking regions or within intronic sequences of the galanin gene have been genotyped with a high-throughput TaqMan OpenArray qPCR system in 526 healthy students (40% males). Depression and anxiety scores were obtained by filling in the Hospital Anxiety and Depression Scale (HADS) questionnaire. Data were analyzed by ANCOVA and Bonferroni correction was applied for multiple testing. Linkage disequilibrium (LD) analysis was used to map two haploblocks in the analyzed region.A single-locus and a haplotype genetic association proved to be statistically significant. In single-marker analysis, the T allele of the rs1042577 SNP within the 3' untranslated region of the galanin gene associated with greater levels of anxiety (HADS scores were 7.05±4.0 vs 6.15±.15; p = 0.000407). Haplotype analysis revealed an association of the rs948854 C_rs4432027_C allele combination with anxiety [F(1,1046) = 4.140, p = 0.042141, η2 = 0.004, power = 0.529]. Neither of these associations turned out to be gender-specific. These promoter polymorphisms are supposed to participate in epigenetic regulation of galanin expression by creating potentially methylatable CpG dinucleotides. The functional importance of the rs1042577_T allele remains to be elucidated

Conserved genes and pathways in primary human fibroblast strains undergoing replicative and radiation induced senescence

Additional file 3: Figure S3. Regulation of genes of Arrhythmogenic right ventricular cardiomyopathy pathway during senescence induction in HFF strains Genes of the “Arrhythmogenic right ventricular cardiomyopathy” pathway which are significantly up- (green) and down- (red) regulated (log2 fold change >1) during irradiation induced senescence (120 h after 20 Gy irradiation) in HFF strains. Orange color signifies genes which are commonly up-regulated during both, irradiation induced and replicative senescence