Risk of Subsequent Coronary Heart Disease in Patients Hospitalized for Immune-Mediated Diseases: A Nationwide Follow-Up Study from Sweden

Background: Certain immune-mediated diseases (IMDs), such as rheumatoid arthritis and systemic lupus erythematosus, have been linked to cardiovascular disorders. We examined whether there is an association between 32 different IMDs and risk of subsequent hospitalization for coronary heart disease (CHD) related to coronary atherosclerosis in a nationwide follow up study in Sweden. Methods and Findings: All individuals in Sweden hospitalized with a main diagnosis of an IMD (n = 336,479) without previous or coexisting CHD, between January 1, 1964 and December 31 2008, were followed for first hospitalization for CHD. The reference population was the total population of Sweden. Standardized incidence ratios (SIRs) for CHD were calculated. Overall risk of CHD during the first year after hospitalization for an IMD was 2.92 (95 % CI 2.84–2.99). Twentyseven of the 32 IMDs studied were associated with an increased risk of CHD during the first year after hospitalization. The overall risk of CHD decreased over time, from 1.75 after 1–5 years (95 % CI 1.73–1.78), to 1.43 after 5–10 years (95 % CI 1.41– 1.46) and 1.28 after 10+ years (95 % CI 1.26–1.30). Females generally had higher SIRs than males. The IMDs for which the SIRs of CDH were highest during the first year after hospitalization included chorea minor 6.98 (95 % CI 1.32–20.65), systemic lupus erythematosus 4.94 (95 % CI 4.15–5.83), rheumatic fever 4.65 (95 % CI 3.53–6.01), Hashimoto’s thyroiditis 4.30 (95 % CI 3.87–4.75), polymyositis/dermatomyositis 3.81 (95 % CI 2.62–5.35), polyarteritis nodosa 3.81 (95 % CI 2.72–5.19), rheumatoi

High Diversity, Low Disparity and Small Body Size in Plesiosaurs (Reptilia, Sauropterygia) from the Triassic–Jurassic Boundary

Invasion of the open ocean by tetrapods represents a major evolutionary transition that occurred independently in cetaceans, mosasauroids, chelonioids (sea turtles), ichthyosaurs and plesiosaurs. Plesiosaurian reptiles invaded pelagic ocean environments immediately following the Late Triassic extinctions. This diversification is recorded by three intensively-sampled European fossil faunas, spanning 20 million years (Ma). These provide an unparalleled opportunity to document changes in key macroevolutionary parameters associated with secondary adaptation to pelagic life in tetrapods. A comprehensive assessment focuses on the oldest fauna, from the Blue Lias Formation of Street, and nearby localities, in Somerset, UK (Earliest Jurassic: 200 Ma), identifying three new species representing two small-bodied rhomaleosaurids (Stratesaurus taylori gen et sp. nov.; Avalonnectes arturi gen. et sp. nov) and the most basal plesiosauroid, Eoplesiosaurus antiquior gen. et sp. nov. The initial radiation of plesiosaurs was characterised by high, but short-lived, diversity of an archaic clade, Rhomaleosauridae. Representatives of this initial radiation were replaced by derived, neoplesiosaurian plesiosaurs at small-medium body sizes during a more gradual accumulation of morphological disparity. This gradualistic modality suggests that adaptive radiations within tetrapod subclades are not always characterised by the initially high levels of disparity observed in the Paleozoic origins of major metazoan body plans, or in the origin of tetrapods. High rhomaleosaurid diversity immediately following the Triassic-Jurassic boundary supports the gradual model of Late Triassic extinctions, mostly predating the boundary itself. Increase in both maximum and minimum body length early in plesiosaurian history suggests a driven evolutionary trend. However, Maximum-likelihood models suggest only passive expansion into higher body size categories

Information in small neuronal ensemble activity in the hippocampal CA1 during delayed non-matching to sample performance in rats

<p>Abstract</p> <p>Background</p> <p>The matrix-like organization of the hippocampus, with its several inputs and outputs, has given rise to several theories related to hippocampal information processing. Single-cell electrophysiological studies and studies of lesions or genetically altered animals using recognition memory tasks such as delayed non-matching-to-sample (DNMS) tasks support the theories. However, a complete understanding of hippocampal function necessitates knowledge of the encoding of information by multiple neurons in a single trial. The role of neuronal ensembles in the hippocampal CA1 for a DNMS task was assessed quantitatively in this study using multi-neuronal recordings and an artificial neural network classifier as a decoder.</p> <p>Results</p> <p>The activity of small neuronal ensembles (6-18 cells) over brief time intervals (2-50 ms) contains accurate information specifically related to the matching/non-matching of continuously presented stimuli (stimulus comparison). The accuracy of the combination of neurons pooled over all the ensembles was markedly lower than those of the ensembles over all examined time intervals.</p> <p>Conclusion</p> <p>The results show that the spatiotemporal patterns of spiking activity among cells in the small neuronal ensemble contain much information that is specifically useful for the stimulus comparison. Small neuronal networks in the hippocampal CA1 might therefore act as a comparator during recognition memory tasks.</p

Amplified B Lymphocyte CD40 Signaling Drives Regulatory B10 Cell Expansion in Mice

Aberrant CD40 ligand (CD154) expression occurs on both T cells and B cells in human lupus patients, which is suggested to enhance B cell CD40 signaling and play a role in disease pathogenesis. Transgenic mice expressing CD154 by their B cells (CD154(TG)) have an expanded spleen B cell pool and produce autoantibodies (autoAbs). CD22 deficient (CD22(-/-)) mice also produce autoAbs, and importantly, their B cells are hyper-proliferative following CD40 stimulation ex vivo. Combining these 2 genetic alterations in CD154(TG)CD22(-/-) mice was thereby predicted to intensify CD40 signaling and autoimmune disease due to autoreactive B cell expansion and/or activation.CD154(TG)CD22(-/-) mice were assessed for their humoral immune responses and for changes in their endogenous lymphocyte subsets. Remarkably, CD154(TG)CD22(-/-) mice were not autoimmune, but instead generated minimal IgG responses against both self and foreign antigens. This paucity in IgG isotype switching occurred despite an expanded spleen B cell pool, higher serum IgM levels, and augmented ex vivo B cell proliferation. Impaired IgG responses in CD154(TG)CD22(-/-) mice were explained by a 16-fold expansion of functional, mature IL-10-competent regulatory spleen B cells (B10 cells: 26.7×10(6)±6 in CD154(TG)CD22(-/-) mice; 1.7×10(6)±0.4 in wild type mice, p<0.01), and an 11-fold expansion of B10 cells combined with their ex vivo-matured progenitors (B10+B10pro cells: 66×10(6)±3 in CD154(TG)CD22(-/-) mice; 6.1×10(6)±2 in wild type mice, p<0.01) that represented 39% of all spleen B cells.These results demonstrate for the first time that the IL-10-producing B10 B cell subset has the capacity to suppress IgG humoral immune responses against both foreign and self antigens. Thereby, therapeutic agents that drive regulatory B10 cell expansion in vivo may inhibit pathogenic IgG autoAb production in humans

Dual coding with STDP in a spiking recurrent neural network model of the hippocampus.

The firing rate of single neurons in the mammalian hippocampus has been demonstrated to encode for a range of spatial and non-spatial stimuli. It has also been demonstrated that phase of firing, with respect to the theta oscillation that dominates the hippocampal EEG during stereotype learning behaviour, correlates with an animal's spatial location. These findings have led to the hypothesis that the hippocampus operates using a dual (rate and temporal) coding system. To investigate the phenomenon of dual coding in the hippocampus, we examine a spiking recurrent network model with theta coded neural dynamics and an STDP rule that mediates rate-coded Hebbian learning when pre- and post-synaptic firing is stochastic. We demonstrate that this plasticity rule can generate both symmetric and asymmetric connections between neurons that fire at concurrent or successive theta phase, respectively, and subsequently produce both pattern completion and sequence prediction from partial cues. This unifies previously disparate auto- and hetero-associative network models of hippocampal function and provides them with a firmer basis in modern neurobiology. Furthermore, the encoding and reactivation of activity in mutually exciting Hebbian cell assemblies demonstrated here is believed to represent a fundamental mechanism of cognitive processing in the brain

Risk of subsequent ischemic and hemorrhagic stroke in patients hospitalized for immune-mediated diseases: a nationwide follow-up study from Sweden

Background: Certain immune-mediated diseases (IMDs) have been associated with increased risk for cardiovascular disorders. The aim of the present study was to examine whether there is an association between 32 different IMDs and first hospitalization for ischemic or hemorrhagic stroke. Methods: All individuals in Sweden hospitalized with a main diagnosis of IMD (without previous or coexisting stroke), between January 1, 1987 and December 31, 2008 (n = 216,291), were followed for first hospitalization for ischemic or hemorrhagic stroke. The reference population was the total population of Sweden. Adjusted standardized incidence ratios (SIRs) for ischemic and hemorrhagic stroke were calculated. Results: Totally 20 and 15 of the 32 IMDs studied, respectively, were associated with an increased risk of ischemic and hemorrhagic stroke during the follow-up. The overall risks of ischemic and hemorrhagic stroke during the first year after hospitalization for IMD were 2.02 (95 % CI 1.90-2.14) and 2.65 (95 % CI 2.27-3.08), respectively. The overall risk of ischemic or hemorrhagic stroke decreased over time, to 1.50 (95 % CI 1.46-1.55) and 1.83 (95 % CI 1.69-1.98), respectively, after 1-5 years, and 1.29 (95 % CI 1.23-1.35) and 1.47 (95 % CI 1.31-1.65), respectively, after 10+ years. The risk of hemorrhagic stroke was >= 2 during the first year after hospitalization for seven IMDs: ankylosing spondylitis (SIR = 8.11), immune thrombocytopenic purpura (SIR = 8.60), polymyalgia rheumatica (SIR = 2.06), psoriasis (SIR = 2.88), rheumatoid arthritis (SIR = 3.27), systemic lupus erythematosus (SIR = 8.65), and Wegener ' s granulomatosis (SIR = 5.83). The risk of ischemic stroke was >= 2 during the first year after hospitalization for twelve IMDs: Addison's disease (SIR = 2.71), Crohn's disease (SIR = 2.15), Grave's disease (SIR = 2.15), Hashimoto's thyroiditis (SIR = 2.99), immune thrombocytopenic purpura (SIR = 2.35), multiple sclerosis (SIR = 3.05), polymyositis/dermatomyositis (SIR = 3.46), rheumatic fever (SIR = 3.91), rheumatoid arthritis (SIR = 2.08), Sjgren's syndrome (SIR = 2.57), systemic lupus erythematosus (SIR = 2.21), and ulcerative colitis (SIR = 2.15). Conclusions: Hospitalization for many IMDs is associated with increased risk of ischemic or hemorrhagic stroke. The findings suggest that several IMDs are linked to cerebrovascular disease

Alcohol consumption and carotid artery structure in Korean adults aged 50 years and older

<p>Abstract</p> <p>Background</p> <p>Epidemiologic studies of the association between alcohol consumption and carotid artery structure have reported conflicting results. We investigated the association between alcohol consumption and carotid atherosclerosis by evaluating the effects of alcohol intake on carotid artery enlargement.</p> <p>Methods</p> <p>The study population consisted of 4302 community-dwelling Koreans (1577 men and 2725 women) aged 50 years and over. All the subjects had participated in the baseline survey of the Dong-gu Study conducted between 2007 and 2008. Daily alcohol consumption was determined by the number and frequency of alcoholic beverages consumed. We measured common carotid artery intima-media thickness (CCA-IMT), common carotid and bulb IMT (CB-IMT), carotid plaques, and the diameter of the common carotid artery (CCA-diameter) using high-resolution B-mode ultrasonography. We used analysis of covariance and multiple logistic regressions to determine the relationship between alcohol consumption and carotid artery parameters.</p> <p>Results</p> <p>CCA-IMT and CB-IMT were negatively correlated with alcohol consumption after controlling for cardiovascular risk factors in men (<it>p </it>for linear trend = 0.009 and = 0.038, respectively). The multivariate-adjusted odds ratio (OR) for carotid plaques was significantly higher in men who consumed >40.0 g/d (OR = 1.81, 95% CI = 1.13-2.91), although a significant positive correlation was observed between alcohol consumption and carotid plaques (<it>p </it>for linear trend = 0.027). Neither carotid IMT nor carotid plaques were correlated with alcohol intake in women. Alcohol intake was positively correlated with CCA-diameter adjusted for carotid IMT and plaques in the multivariate-adjusted model in both sexes (<it>p </it>for linear trend <0.001 for men and 0.020 for women).</p> <p>Conclusion</p> <p>The results of our study indicate that alcohol consumption is inversely related to carotid IMT and positively related to carotid plaques in men, but not women. However, alcohol intake is positively associated with CCA-diameter in both men and women. Additional large population-based prospective studies are needed to confirm the effects of alcohol consumption on carotid artery structure.</p

Effects of Vegetation, Corridor Width and Regional Land Use on Early Successional Birds on Powerline Corridors

Powerline rights-of-way (ROWs) often provide habitat for early successional bird species that have suffered long-term population declines in eastern North America. To determine how the abundance of shrubland birds varies with habitat within ROW corridors and with land use patterns surrounding corridors, we ran Poisson regression models on data from 93 plots on ROWs and compared regression coefficients. We also determined nest success rates on a 1-km stretch of ROW. Seven species of shrubland birds were common in powerline corridors. However, the nest success rates for prairie warbler (Dendroica discolor) and field sparrow (Spizella pusilla) were <21%, which is too low to compensate for estimated annual mortality. Some shrubland bird species were more abundant on narrower ROWs or at sites with lower vegetation or particular types of vegetation, indicating that vegetation management could be refined to favor species of high conservation priority. Also, several species were more abundant in ROWs traversing unfragmented forest than those near residential areas or farmland, indicating that corridors in heavily forested regions may provide better habitat for these species. In the area where we monitored nests, brood parasitism by brown-headed cowbirds (Molothrus ater) occurred more frequently close to a residential area. Although ROWs support dense populations of shrubland birds, those in more heavily developed landscapes may constitute sink habitat. ROWs in extensive forests may contribute more to sustaining populations of early successional birds, and thus may be the best targets for habitat management

Representing 3D Space in Working Memory: Spatial Images from Vision, Hearing, Touch, and Language

The chapter deals with a form of transient spatial representation referred to as a spatial image. Like a percept, it is externalized, scaled to the environment, and can appear in any direction about the observer. It transcends the concept of modality, as it can be based on inputs from the three spatial senses, from language, and from long-term memory. Evidence is presented that supports each of the claimed properties of the spatial image, showing that it is quite different from a visual image. Much of the evidence presented is based on spatial updating. A major concern is whether spatial images from different input modalities are functionally equivalent— that once instantiated in working memory, the spatial images from different modalities have the same functional characteristics with respect to subsequent processing, such as that involved in spatial updating. Going further, the research provides some evidence that spatial images are amodal (i.e., do not retain modality-specific features)

New technologies for examining neuronal ensembles in drug addiction and fear

Correlational data suggest that learned associations are encoded within neuronal ensembles. However, it has been difficult to prove that neuronal ensembles mediate learned behaviours because traditional pharmacological and lesion methods, and even newer cell type-specific methods, affect both activated and non-activated neurons. Additionally, previous studies on synaptic and molecular alterations induced by learning did not distinguish between behaviourally activated and non-activated neurons. Here, we describe three new approaches—Daun02 inactivation, FACS sorting of activated neurons and c-fos-GFP transgenic rats — that have been used to selectively target and study activated neuronal ensembles in models of conditioned drug effects and relapse. We also describe two new tools — c-fos-tTA mice and inactivation of CREB-overexpressing neurons — that have been used to study the role of neuronal ensembles in conditioned fear