Reperfusion therapy for ST elevation acute myocardial infarction 2010/2011: current status in 37 ESC countries

AIMS Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion therapy in ST-elevation myocardial infarction (STEMI). We conducted this study to evaluate the contemporary status on the use and type of reperfusion therapy in patients admitted with STEMI in the European Society of Cardiology (ESC) member countries. METHODS AND RESULTS A cross-sectional descriptive study based on aggregated country-level data on the use of reperfusion therapy in patients admitted with STEMI during 2010 or 2011. Thirty-seven ESC countries were able to provide data from existing national or regional registries. In countries where no such registries exist, data were based on best expert estimates. Data were collected on the use of STEMI reperfusion treatment and mortality, the numbers of cardiologists, and the availability of PPCI facilities in each country. Our survey provides a brief data summary of the degree of variation in reperfusion therapy across Europe. The number of PPCI procedures varied between countries, ranging from 23 to 884 per million inhabitants. Primary percutaneous coronary intervention and thrombolysis were the dominant reperfusion strategy in 33 and 4 countries, respectively. The mean population served by a single PPCI centre with a 24-h service 7 days a week ranged from 31 300 inhabitants per centre to 6 533 000 inhabitants per centre. Twenty-seven of the total 37 countries participated in a former survey from 2007, and major increases in PPCI utilization were observed in 13 of these countries. CONCLUSION Large variations in reperfusion treatment are still present across Europe. Countries in Eastern and Southern Europe reported that a substantial number of STEMI patients are not receiving any reperfusion therapy. Implementation of the best reperfusion therapy as recommended in the guidelines should be encouraged.

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.

Geographic distribution and molecular diversity of Bartonella infections in moose, Alces alces, in Finland.

Moose, Alces alces (Artiodactyla: Cervidae) in Finland are heavily infested with deer keds, Lipoptena cervi (Diptera: Hippoboschidae). The deer ked, which carries species of the genus Bartonella, has been proposed as a vector for the transmission of bartonellae to animals and humans. Previously, bartonella DNA was found in deer keds as well as in moose blood collected in Finland. We investigated the prevalence and molecular diversity of Bartonella spp. infection from blood samples collected from free-ranging moose. Given that the deer ked is not present in northernmost Finland, we also investigated whether there were geographic differences in the prevalence of bartonella infection in moose. The overall prevalence of bartonella infection was 72.9% (108/148). Geographically, the prevalence was highest in the south (90.6%) and lowest in the north (55.9%). At least two species of bartonellae were identified by multilocus sequence analysis. Based on logistic regression analysis, there was no significant association between bartonella infection and either age or sex; however, moose from outside the deer ked zone were significantly less likely to be infected (P<0.015) than were moose hunted within the deer ked zone.

Prevalence estimation of tick-borne encephalitis virus (TBEV) antibodies in dogs from Finland using novel dog anti-TBEV IgG MAb-capture and IgG immunofluorescence assay based on recombinant TBEV subviral particles

Tick-borne encephalitis (TBE) is one of the most dangerous human neurological infections occurring in Europe and Northern parts of Asia with thousands of cases and millions vaccinated against it. The risk of TBE might be assessed through analyses of the samples taken from wildlife or from animals which are in close contact with humans. Dogs have been shown to be a good sentinel species for these studies. Serological assays for diagnosis of TBE in dogs are mainly based on purified and inactivated TBEV antigens. Here we describe novel dog anti-TBEV IgG monoclonal antibody (MAb)-capture assay which is based on TBEV prME subviral particles expressed in mammalian cells from Semliki Forest virus (SFV) replicon as well as IgG immunofluorescence assay (IFA) which is based on Vero E6 cells transfected with the same SFV replicon. We further demonstrate their use in a small-scale TBEV seroprevalence study of dogs representing different regions of Finland. Altogether, 148 dog serum samples were tested by novel assays and results were compared to those obtained with a commercial IgG enzyme immunoassay (EIA), hemagglutination inhibition test and IgG IFA with TBEV infected cells. Compared to reference tests, the sensitivities of the developed assays were 90-100% and the specificities of the two assays were 100%. Analysis of the dog serum samples showed a seroprevalence of 40% on Åland Islands and 6% on Southwestern archipelago of Finland. In conclusion, a specific and sensitive EIA and IFA for the detection of IgG antibodies in canine sera were developed. Based on these assays the seroprevalence of IgG antibodies in dogs from different regions of Finland was assessed and was shown to parallel the known human disease burden as the Southwestern archipelago and Åland Islands in particular had considerable dog TBEV antibody prevalence and represent areas with high risk of TBE for humans.

(Table 1) Characteristics of snow pits on De Geerfonna and Vestfonna during the IPY 2007-2010

Extensive glaciological field measurements were carried out on the ice cap Vestfonna as well as on the minor ice body De Geerfonna (Nordaustlandet, Svalbard) within the framework of IPY Kinnvika. Field campaigns were conducted during the period 2007-2010 in spring (April/May) and summer (August). In this study we compile and present snow cover information obtained from 22 snow pits that were dug on Vestfonna during this period. Locations are along two transects on the northwestern, land terminating slope of the ice cap, on its central summit, Ahlmann Summit, and at a set of several other locations in the eastern and northern part of the ice cap. Snow-cover information acquired from four snow pits on adjacent De Geerfonna is also incorporated in this study. Field data are analysed regarding snow stratigraphy, snow density, snow hardness and snow temperature. Results reveal mean snow densities of around 400 kg/m**3 for the snowpack of Vestfonna with no apparent spatial or interannual variability. A distinctly higher value of more than 450 kg/m**3 was obtained for De Geerfonna. A spatial comparison of snow water equivalents above the previous end-of-summer surface serves for obtaining insights into the spatial distribution of snow accumulation across Vestfonna. Altitude was found to be the only significant spatial parameter for controlling snow accumulation across the ice cap.

Activation of Androgen Receptor Function by a Novel Nuclear Protein Kinase

Androgen receptor (AR) belongs to the nuclear receptor superfamily and mediates the biological actions of male sex steroids. In this work, we have characterized a novel 130-kDa Ser/Thr protein kinase ANPK that interacts with the zinc finger region of AR in vivo and in vitro. The catalytic kinase domain of ANPK shares considerable sequence similarity with the minibrain gene product, a protein kinase suggested to contribute to learning defects associated with Down syndrome. However, the rest of ANPK sequence, including the AR-interacting interface, exhibits no apparent homology with other proteins. ANPK is a nuclear protein that is widely expressed in mammalian tissues. Its overexpression enhances AR-dependent transcription in various cell lines. In addition to the zinc finger region, ligand-binding domain and activation function AF1 of AR are needed, as the activity of AR mutants devoid of these domains was not influenced by ANPK. The receptor protein does not appear to be a substrate for ANPK in vitro, and overexpression of ANPK does not increase the extent of AR phosphorylation in vivo. In view of this, it is likely that ANPK-mediated activation of AR function is exerted through modification of AR-associated proteins, such as coregulatory factors, and/or through stabilization of the receptor protein against degradation.

Phosphorylated Human Keratinocyte Ornithine Decarboxylase Is Preferentially Associated with Insoluble Cellular Proteins

Ornithine decarboxylase (ODC), the first enzyme in polyamine biosynthesis, is highly regulated by many trophic stimuli, and changes in its levels and organization correlate with cytoskeletal changes in normal human epidermal keratinocytes (NHEK). NHEK ODC exhibits a filamentous perinuclear/nuclear localization that becomes more diffuse under conditions that alter actin architecture. We have thus asked whether ODC colocalizes with a component of the NHEK cytoskeleton. Confocal immunofluorescence showed that ODC distribution in NHEK was primarily perinuclear; upon disruption of the actin cytoskeleton with cytochalasin D, ODC distribution was diffuse. The ODC distribution in untreated NHEK overlapped with that of keratin in the perinuclear but not cytoplasmic area; after treatment with cytochalasin D, overlap between staining for ODC and for keratin was extensive. No significant overlap with actin and minimal overlap with tubulin filament systems were observed. Subcellular fractionation by sequential homogenizations and centrifugations of NHEK lysates or detergent and salt extractions of NHEK in situ revealed that ODC protein and activity were detectable in both soluble and insoluble fractions, with mechanical disruption causing additional solubilization of ODC activity (three- to sevenfold above controls). Fractionation and ODC immunoprecipitation from [32P]orthophosphate-labeled NHEK lysates showed that a phosphorylated form of ODC was present in the insoluble fractions. Taken together, these data suggest that two pools of ODC exist in NHEK. The first is the previously described soluble pool, and the second is enriched in phospho-ODC and associated with insoluble cellular material that by immunohistochemistry appears to be organized in conjunction with the keratin cytoskeleton.

Cortical processing of change detection: Dissociation between natural vowels and two-frequency complex tones

We compared magnetoencephalographic responses for natural vowels and for sounds consisting of two pure tones that represent the two lowest formant frequencies of these vowels. Our aim was to determine whether spectral changes in successive stimuli are detected differently for speech and nonspeech sounds. The stimuli were presented in four blocks applying an oddball paradigm (20% deviants, 80% standards): (i) /α/ tokens as deviants vs. /i/ tokens as standards; (ii) /e/ vs. /i/; (iii) complex tones representing /α/ formants vs. /i/ formants; and (iv) complex tones representing /e/ formants vs. /i/ formants. Mismatch fields (MMFs) were calculated by subtracting the source waveform produced by standards from that produced by deviants. As expected, MMF amplitudes for the complex tones reflected acoustic deviation: the amplitudes were stronger for the complex tones representing /α/ than /e/ formants, i.e., when the spectral difference between standards and deviants was larger. In contrast, MMF amplitudes for the vowels were similar despite their different spectral composition, whereas the MMF onset time was longer for /e/ than for /α/. Thus the degree of spectral difference between standards and deviants was reflected by the MMF amplitude for the nonspeech sounds and by the MMF latency for the vowels.

Global warming in the twenty-first century: An alternative scenario

A common view is that the current global warming rate will continue or accelerate. But we argue that rapid warming in recent decades has been driven mainly by non-CO2 greenhouse gases (GHGs), such as chlorofluorocarbons, CH4, and N2O, not by the products of fossil fuel burning, CO2 and aerosols, the positive and negative climate forcings of which are partially offsetting. The growth rate of non-CO2 GHGs has declined in the past decade. If sources of CH4 and O3 precursors were reduced in the future, the change in climate forcing by non-CO2 GHGs in the next 50 years could be near zero. Combined with a reduction of black carbon emissions and plausible success in slowing CO2 emissions, this reduction of non-CO2 GHGs could lead to a decline in the rate of global warming, reducing the danger of dramatic climate change. Such a focus on air pollution has practical benefits that unite the interests of developed and developing countries. However, assessment of ongoing and future climate change requires composition-specific long-term global monitoring of aerosol properties.

ANX7, a candidate tumor suppressor gene for prostate cancer

The ANX7 gene is located on human chromosome 10q21, a site long hypothesized to harbor a tumor suppressor gene(s) (TSG) associated with prostate and other cancers. To test whether ANX7 might be a candidate TSG, we examined the ANX7-dependent suppression of human tumor cell growth, stage-specific ANX7 expression in 301 prostate specimens on a prostate tissue microarray, and loss of heterozygosity (LOH) of microsatellite markers at or near the ANX7 locus. Here we report that human tumor cell proliferation and colony formation are markedly reduced when the wild-type ANX7 gene is transfected into two prostate tumor cell lines, LNCaP and DU145. Consistently, analysis of ANX7 protein expression in human prostate tumor microarrays reveals a significantly higher rate of loss of ANX7 expression in metastatic and local recurrences of hormone refractory prostate cancer as compared with primary tumors (P = 0.0001). Using four microsatellite markers at or near the ANX7 locus, and laser capture microdissected tumor cells, 35% of the 20 primary prostate tumors show LOH. The microsatellite marker closest to the ANX7 locus showed the highest rate of LOH, including one homozygous deletion. We conclude that the ANX7 gene exhibits many biological and genetic properties expected of a TSG and may play a role in prostate cancer progression.