Determination of Pericardial Adipose Tissue Increases the Prognostic Accuracy of Coronary Artery Calcification for Future Cardiovascular Events

Objectives: Pericardial adipose tissue (PAT) is associated with coronary artery plaque accumulation and the incidence of coronary heart disease. We evaluated the possible incremental prognostic value of PAT for future cardiovascular events. Methods: 145 patients (94 males, age 60 10 years) with stable coronary artery disease underwent coronary artery calcification (CAC) scanning in a multislice CT scanner, and the volume of pericardial fat was measured. Mean observation time was 5.4 years. Results: 34 patients experienced a severe cardiac event. They had a significantly higher CAC score (1,708 +/- 2,269 vs. 538 +/- 1,150, p 400, 3.5 (1.9-5.4; p = 0.007) for scores > 800 and 5.9 (3.7-7.8; p = 0.005) for scores > 1,600. When additionally a PAT volume > 200 cm(3) was determined, there was a significant increase in the event rate and relative risk. We calculated a relative risk of 2.9 (1.9-4.2; p = 0.01) for scores > 400, 4.0 (2.1-5.0; p = 0.006) for scores > 800 and 7.1 (4.1-10.2; p = 0.005) for scores > 1,600. Conclusions:The additional determination of PAT increases the predictive power of CAC for future cardiovascular events. PAT might therefore be used as a further parameter for risk stratification. Copyright (C) 2012 S. Karger AG, Base

Effective Dark Matter Model: Relic density, CDMS II, Fermi LAT and LHC

The Cryogenic Dark Matter Search recently announced the observation of two signal events with a 77% confidence level. Although statistically inconclusive, it is nevertheless suggestive. In this work we present a model-independent analysis on the implication of a positive signal in dark matter scattering off nuclei. Assuming the interaction between (scalar, fermion or vector) dark matter and the standard model induced by unknown new physics at the scale $\Lambda$, we examine various dimension-6 tree-level induced operators and constrain them using the current experimental data, e.g. the WMAP data of the relic abundance, CDMS II direct detection of the spin-independent scattering, and indirect detection data (Fermi LAT cosmic gamma-ray), etc. Finally, the LHC reach is also explored

Active inference, sensory attenuation and illusions.

Active inference provides a simple and neurobiologically plausible account of how action and perception are coupled in producing (Bayes) optimal behaviour. This can be seen most easily as minimising prediction error: we can either change our predictions to explain sensory input through perception. Alternatively, we can actively change sensory input to fulfil our predictions. In active inference, this action is mediated by classical reflex arcs that minimise proprioceptive prediction error created by descending proprioceptive predictions. However, this creates a conflict between action and perception; in that, self-generated movements require predictions to override the sensory evidence that one is not actually moving. However, ignoring sensory evidence means that externally generated sensations will not be perceived. Conversely, attending to (proprioceptive and somatosensory) sensations enables the detection of externally generated events but precludes generation of actions. This conflict can be resolved by attenuating the precision of sensory evidence during movement or, equivalently, attending away from the consequences of self-made acts. We propose that this Bayes optimal withdrawal of precise sensory evidence during movement is the cause of psychophysical sensory attenuation. Furthermore, it explains the force-matching illusion and reproduces empirical results almost exactly. Finally, if attenuation is removed, the force-matching illusion disappears and false (delusional) inferences about agency emerge. This is important, given the negative correlation between sensory attenuation and delusional beliefs in normal subjects--and the reduction in the magnitude of the illusion in schizophrenia. Active inference therefore links the neuromodulatory optimisation of precision to sensory attenuation and illusory phenomena during the attribution of agency in normal subjects. It also provides a functional account of deficits in syndromes characterised by false inference and impaired movement--like schizophrenia and Parkinsonism--syndromes that implicate abnormal modulatory neurotransmission

Hippocampal - diencephalic - cingulate networks for memory and emotion: An anatomical guide

This review brings together current knowledge from tract tracing studies to update and reconsider those limbic connections initially highlighted by Papez for their presumed role in emotion. These connections link hippocampal and parahippocampal regions with the mammillary bodies, the anterior thalamic nuclei, and the cingulate gyrus, all structures now strongly implicated in memory functions. An additional goal of this review is to describe the routes taken by the various connections within this network. The original descriptions of these limbic connections saw their interconnecting pathways forming a serial circuit that began and finished in the hippocampal formation. It is now clear that with the exception of the mammillary bodies, these various sites are multiply interconnected with each other, including many reciprocal connections. In addition, these same connections are topographically organised, creating further subsystems. This complex pattern of connectivity helps explain the difficulty of interpreting the functional outcome of damage to any individual site within the network. For these same reasons, Papez’s initial concept of a loop beginning and ending in the hippocampal formation needs to be seen as a much more complex system of hippocampal–diencephalic–cingulate connections. The functions of these multiple interactions might be better viewed as principally providing efferent information from the posterior medial temporal lobe. Both a subcortical diencephalic route (via the fornix) and a cortical cingulate route (via retrosplenial cortex) can be distinguished. These routes provide indirect pathways for hippocampal interactions with prefrontal cortex, with the preponderance of both sets of connections arising from the more posterior hippocampal regions. These multi-stage connections complement the direct hippocampal projections to prefrontal cortex, which principally arise from the anterior hippocampus, thereby creating longitudinal functional differences along the anterior–posterior plane of the hippocampus

Refinement and Pattern Formation in Neural Circuits by the Interaction of Traveling Waves with Spike-Timing Dependent Plasticity

Traveling waves in the developing brain are a prominent source of highly correlated spiking activity that may instruct the refinement of neural circuits. A candidate mechanism for mediating such refinement is spike-timing dependent plasticity (STDP), which translates correlated activity patterns into changes in synaptic strength. To assess the potential of these phenomena to build useful structure in developing neural circuits, we examined the interaction of wave activity with STDP rules in simple, biologically plausible models of spiking neurons. We derive an expression for the synaptic strength dynamics showing that, by mapping the time dependence of STDP into spatial interactions, traveling waves can build periodic synaptic connectivity patterns into feedforward circuits with a broad class of experimentally observed STDP rules. The spatial scale of the connectivity patterns increases with wave speed and STDP time constants. We verify these results with simulations and demonstrate their robustness to likely sources of noise. We show how this pattern formation ability, which is analogous to solutions of reaction-diffusion systems that have been widely applied to biological pattern formation, can be harnessed to instruct the refinement of postsynaptic receptive fields. Our results hold for rich, complex wave patterns in two dimensions and over several orders of magnitude in wave speeds and STDP time constants, and they provide predictions that can be tested under existing experimental paradigms. Our model generalizes across brain areas and STDP rules, allowing broad application to the ubiquitous occurrence of traveling waves and to wave-like activity patterns induced by moving stimuli

Cortisol secretion after adrenocorticotrophin (ACTH) and Dexamethasone tests in healthy female and male dogs

<p>Abstract</p> <p>Background</p> <p>For the conclusive diagnosis of Cushing's Syndrome, a stimulating ACTH test or a low suppressive Dexamethasone test is used. Reports in other species than the dog indicate that plasma cortisol concentration after ACTH administration is affected by gender. We investigated the effect of gender on the cortisol response to ACTH and Dexamethasone tests in dogs.</p> <p>Methods</p> <p>Seven healthy adult Cocker Spaniels (4 females and 3 males) were assigned to a two by two factorial design: 4 dogs (2 females and 2 males) received IV Dexamethasone 0.01 mg/kg, while the other 3 dogs received an IV saline solution (control group). Two weeks later the treatments were reversed. After one month, ACTH was given IV (250 μg/animal) to 4 dogs (2 female and 2 males) while the rest was treated with saline solution (control group). Cortisol concentrations were determined by a direct solid-phase radioimmunoassay and cholesterol and triglycerides by commercial kits.</p> <p>Results and Discussion</p> <p>No effect of treatment was observed in metabolite concentrations, but females presented higher cholesterol concentrations. ACTH-treated dogs showed an increase in cortisol levels in the first hour after sampling until 3 hours post injection. Cortisol concentrations in Dexamethasone-treated dogs decreased one hour post injection and remained low for 3 hours, thereafter cortisol concentrations increased. The increase in cortisol levels from one to two hours post ACTH injection was significantly higher in females than males. In Dexamethasone-treated males cortisol levels decreased one hour post injection up to 3 hours; in females the decrease was more pronounced and prolonged, up to 5 hours post injection.</p> <p>Conclusion</p> <p>We have demonstrated that cortisol response to ACTH and Dexamethasone treatment in dogs differs according to sex.</p

Serum testosterone levels of HbSS (sickle cell disease) male subjects in Lagos, Nigeria

<p>Abstract</p> <p>Background</p> <p>Infertility is a major problem in sickle cell disease patients, especially in males. In addition to low serum testosterone, other abnormalities involving the accessory sex organs, such as the seminal vesicles and the prostate gland, as well as marked decrease in ejaculate volume may be observed in male HbSS patients. Hence, the need to study the role of sex hormones as a cause of infertility in male HbSS patients.</p> <p>Methods</p> <p>An unmatched case-control study was performed using seventy-five consenting subjects from Lagos University Teaching Hospital. These included 47 patients with haemoglobin phenotype SS from the Sickle cell clinic and 28 volunteered medical students and members of staff with haemoglobin phenotype AA. Demographic data were obtained using a self-administered questionnaire. A total of 5 mls of blood was collected from each subject between 9.00 am & 11.am, and assayed for serum testosterone concentration.</p> <p>Results</p> <p>The concentrations of serum testosterone in HbSS patients ranged from 0.2 to 4.3 ng/ml with a mean of 1.28 ± 0.72 ng/ml whilst the values in HbAA controls ranged from 1.2 to 6.9 ng/ml with a mean of 2.63 ± 1.04 ng/ml. Seven (25.0%) of the 28 controls had serum testosterone concentration lower than the quoted reference (normal) range whereas 44 (93.6%) of the 47 HbSS subjects had serum testosterone concentration lower than the reference range.</p> <p>Conclusion</p> <p>Overall, subjects with HbSS have significantly lower mean serum testosterone than HbAA controls.</p

Physicians are a key to encouraging cessation of smoking among people living with HIV/AIDS: a cross-sectional study in the Kathmandu Valley, Nepal

BackgroundHIV care providers may be optimally positioned to promote smoking behaviour change in their patients, among whom smoking is both highly prevalent and uniquely harmful. Yet research on this front is scant, particularly in the developing country context. Hence, this study describes smoking behaviour among people living with HIV/AIDS (PLWHA) in the Kathmandu Valley of Nepal, and assesses the association between experience of physician-delivered smoking status assessment and readiness to quit among HIV-positive smokers.MethodsWe conducted a cross-sectional survey of PLWHA residing in the Kathmandu Valley, Nepal. Data from 321 adult PLWHA were analyzed using multiple logistic regression for correlates of current smoking and, among current smokers, of motivational readiness to quit based on the transtheoretical model (TTM) of behaviour change.ResultsOverall, 47% of participants were current smokers, with significantly higher rates among men (72%), ever- injecting drug users (IDUs), recent (30-day) alcohol consumers, those without any formal education, and those with higher HIV symptom burdens. Of 151 current smokers, 34% were thinking seriously of quitting within the next 6 months (contemplation or preparation stage of behaviour change). Adjusting for potential confounders, experience of physician-delivered smoking status assessment during any visit to a hospital or clinic in the past 12 months was associated with greater readiness to quit smoking (AOR = 3.34; 95% CI = 1.05,10.61).ConclusionsRoughly one-third of HIV-positive smokers residing in the Kathmandu Valley, Nepal, are at the contemplation or preparation stage of smoking behaviour change, with rates significantly higher among those whose physicians have asked about their smoking status during any clinical interaction over the past year. Systematic screening for smoking by physicians during routine HIV care may help to reduce the heavy burden of smoking and smoking-related morbidity and mortality within HIV-positive populations in Nepal and similar settings

The vitamin D, ionised calcium and parathyroid hormone axis of cerebral capillary function: Therapeutic considerations for vascular-based neurodegenerative disorders

Blood-brain barrier dysfunction characterised by brain parenchymal extravasation of plasma proteins may contribute to risk of neurodegenerative disorders, however the mechanisms for increased capillary permeability are not understood. Increasing evidence suggests vitamin D confers central nervous system benefits and there is increasing demand for vitamin D supplementation. Vitamin D may influence the CNS via modulation of capillary function, however such effects may be indirect as it has a central role in maintaining calcium homeostasis, in concert with calcium regulatory hormones. This study utilised an integrated approach and investigated the effects of vitamin D supplementation, parathyroid tissue ablation (PTX), or exogenous infusion of parathyroid hormone (PTH) on cerebral capillary integrity. Parenchymal extravasation of immunoglobulin G (IgG) was used as a marker of cerebral capillary permeability. In C57BL/6J mice and Sprague Dawley rats, dietary vitamin D was associated with exaggerated abundance of IgG within cerebral cortex (CTX) and hippocampal formation (HPF). Vitamin D was also associated with increased plasma ionised calcium (iCa) and decreased PTH. A response to dose was suggested and parenchymal effects persisted for up to 24 weeks. Ablation of parathyroid glands increased CTX- and HPF-IgG abundance concomitant with a reduction in plasma iCa. With the provision of PTH, iCa levels increased, however the PTH treated animals did not show increased cerebral permeability. Vitamin D supplemented groups and rats with PTH-tissue ablation showed modestly increased parenchymal abundance of glial-fibrillary acidic protein (GFAP), a marker of astroglial activation. PTH infusion attenuated GFAP abundance. The findings suggest that vitamin D can compromise capillary integrity via a mechanism that is independent of calcium homeostasis. The effects of exogenous vitamin D supplementation on capillary function and in the context of prevention of vascular neurodegenerative conditions should be considered in the context of synergistic effects with calcium modulating hormones

Analysis of the functional conservation of ethylene receptors between maize and Arabidopsis

Ethylene, a regulator of plant growth and development, is perceived by specific receptors that act as negative regulators of the ethylene response. Five ethylene receptors, i.e., ETR1, ERS1, EIN4, ETR2, and ERS2, are present in Arabidopsis and dominant negative mutants of each that confer ethylene insensitivity have been reported. In contrast, maize contains just two types of ethylene receptors: ZmERS1, encoded by ZmERS1a and ZmERS1b, and ZmETR2, encoded by ZmETR2a and ZmETR2b. In this study, we introduced a Cys to Tyr mutation in the transmembrane domain of ZmERS1b and ZmETR2b that is present in the etr1-1 dominant negative mutant and expressed each protein in Arabidopsis. Mutant Zmers1b and Zmetr2b receptors conferred ethylene insensitivity and Arabidopsis expressing Zmers1b or Zmetr2b were larger and exhibited a delay in leaf senescence characteristic of ethylene insensitive Arabidopsis mutants. Zmers1b and Zmetr2b were dominant and functioned equally well in a hemizygous or homozygous state. Expression of the Zmers1b N-terminal transmembrane domain was sufficient to exert dominance over endogenous Arabidopsis ethylene receptors whereas the Zmetr2b N-terminal domain failed to do so. Neither Zmers1b nor Zmetr2b functioned in the absence of subfamily 1 ethylene receptors, i.e., ETR1 and ERS1. These results suggest that Cys65 in maize ZmERS1b and ZmETR2b plays the same role that it does in Arabidopsis receptors. Moreover, the results demonstrate that the mutant maize ethylene receptors are functionally dependent on subfamily 1 ethylene receptors in Arabidopsis, indicating substantial functional conservation between maize and Arabidopsis ethylene receptors despite their sequence divergence