Serum cholesterol levels in neutropenic patients with fever

Hypocholesterolemia, which often accompanies infectious diseases has been suggested to serve as a prognostic marker in hospitalized patients. Even though patients with chemotherapyinduced leukopenia are at high risk of infection and mortality, only limited information is available on serum cholesterol levels in these patients. We therefore measured serum cholesterol levels in 17 patients with hematological malignancies during chemotherapyinduced neutropenia and correlated it with clinical outcome. Patients with fever (>38.5 degreesC) showed a significant decrease in serum cholesterol levels within 24 hours. Eight days after onset of the fever nonsurvivors had significantly lower serum cholesterol levels (median 2.09 mmol/l, range 0.492.79, n=6) compared to survivors (median 3.23 mmol/l, range 1.684.86, n=11). Cholesterol levels in survivors returned to baseline levels at the time of discharge from the hospital. At the onset of fever, serum levels of inflammatory cytokines interleukin-6, tumor necrosis factor (TNF) and soluble TNF receptors p55 and p75 were elevated in all patients, but only TNF and TNF receptor p75 levels were significantly different in survivors and nonsurvivors. Our data suggest that a decrease in serum cholesterol levels is a prognostic marker in neutropenic patients with fever. Release of inflammatory cytokines may in part be responsible for hypocholesterolemia in these patients

Reduction of circulating cholesterol and apolipoprotein levels during sepsis

Sepsis with multiple organ failure is frequently associated with a substantial decrease of cholesterol levels. This decrease of cholesterol is strongly associated with mortality suggesting a direct relation between inflammatory conditions and altered cholesterol homeostasis. The host response during sepsis is mediated by cytokines and growth factors, which are capable of influencing lipid metabolism. Conversely lipoproteins are also capable of modulating cytokine production during the inflammatory response. Therefore the decrease in circulating cholesterol levels seems to play a crucial role in the pathophysiology of sepsis. In this review the interaction between cytokines and lipid metabolism and its clinical consequences will be discussed

Cathepsin B-associated Activation of Amyloidogenic Pathway in Murine Mucopolysaccharidosis Type I Brain Cortex

Mucopolysaccharidosis type I (MPS I) is caused by genetic deficiency of alpha-l-iduronidase and impairment of lysosomal catabolism of heparan sulfate and dermatan sulfate. In the brain, these substrates accumulate in the lysosomes of neurons and glial cells, leading to neuroinflammation and neurodegeneration. Their storage also affects lysosomal homeostasis-inducing activity of several lysosomal proteases including cathepsin B (CATB). In the central nervous system, increased CATB activity has been associated with the deposition of amyloid plaques due to an alternative pro-amyloidogenic processing of the amyloid precursor protein (APP), suggesting a potential role of this enzyme in the neuropathology of MPS I. In this study, we report elevated levels of protein expression and activity of CATB in cortex tissues of 6-month-old MPS I (Idua -/- mice. Besides, increased CATB leakage from lysosomes to the cytoplasm of Idua -/- cortical pyramidal neurons was indicative of damaged lysosomal membranes. The increased CATB activity coincided with an elevated level of the 16-kDa C-terminal APP fragment, which together with unchanged levels of beta-secretase 1 was suggestive for the role of this enzyme in the amyloidogenic APP processing. Neuronal accumulation of Thioflavin-S-positive misfolded protein aggregates and drastically increased levels of neuroinflammatory glial fibrillary acidic protein (GFAP)-positive astrocytes and CD11b-positive activated microglia were observed in Idua -/- cortex by confocal fluorescent microscopy. Together, our results point to the existence of a novel CATB-associated alternative amyloidogenic pathway in MPS I brain induced by lysosomal storage and potentially leading to neurodegeneration

Very special relativity as relativity of dark matter: the Elko connection

In the very special relativity (VSR) proposal by Cohen and Glashow, it was pointed out that invariance under HOM(2) is both necessary and sufficient to explain the null result of the Michelson-Morely experiment. It is the quantum field theoretic demand of locality, or the requirement of P, T, CP, or CT invariance, that makes invariance under the Lorentz group a necessity. Originally it was conjectured that VSR operates at the Planck scale; we propose that the natural arena for VSR is at energies similar to the standard model, but in the dark sector. To this end we provide an ab initio spinor representation invariant under the SIM(2) avatar of VSR and construct a mass dimension one fermionic quantum field of spin one half. This field turns out to be a very close sibling of Elko and it exhibits the same striking property of intrinsic darkness with respect to the standard model fields. In the new construct, the tension between Elko and Lorentz symmetries is fully resolved. We thus entertain the possibility that the symmetries underlying the standard model matter and gauge fields are those of Lorentz, while the event space underlying the dark matter and the dark gauge fields supports the algebraic structure underlying VSR.Comment: 19 pages. Section 5 is new. Published version (modulo a footnote, and a corrected typo

Expression of a barley cystatin gene in maize enhances resistance against phytophagous mites by altering their cysteine-proteases

Phytocystatins are inhibitors of cysteine-proteases from plants putatively involved in plant defence based on their capability of inhibit heterologous enzymes. We have previously characterised the whole cystatin gene family members from barley (HvCPI-1 to HvCPI-13). The aim of this study was to assess the effects of barley cystatins on two phytophagous spider mites, Tetranychus urticae and Brevipalpus chilensis. The determination of proteolytic activity profile in both mite species showed the presence of the cysteine-proteases, putative targets of cystatins, among other enzymatic activities. All barley cystatins, except HvCPI-1 and HvCPI-7, inhibited in vitro mite cathepsin L- and/or cathepsin B-like activities, HvCPI-6 being the strongest inhibitor for both mite species. Transgenic maize plants expressing HvCPI-6 protein were generated and the functional integrity of the cystatin transgene was confirmed by in vitro inhibitory effect observed against T. urticae and B. chilensis protein extracts. Feeding experiments impaired on transgenic lines performed with T. urticae impaired mite development and reproductive performance. Besides, a significant reduction of cathepsin L-like and/or cathepsin B-like activities was observed when the spider mite fed on maize plants expressing HvCPI-6 cystatin. These findings reveal the potential of barley cystatins as acaricide proteins to protect plants against two important mite pests

Visual Learning in Multiple-Object Tracking

Tracking moving objects in space is important for the maintenance of spatiotemporal continuity in everyday visual tasks. In the laboratory, this ability is tested using the Multiple Object Tracking (MOT) task, where participants track a subset of moving objects with attention over an extended period of time. The ability to track multiple objects with attention is severely limited. Recent research has shown that this ability may improve with extensive practice (e.g., from action videogame playing). However, whether tracking also improves in a short training session with repeated trajectories has rarely been investigated. In this study we examine the role of visual learning in multiple-object tracking and characterize how varieties of attention interact with visual learning.Participants first conducted attentive tracking on trials with repeated motion trajectories for a short session. In a transfer phase we used the same motion trajectories but changed the role of tracking targets and nontargets. We found that compared with novel trials, tracking was enhanced only when the target subset was the same as that used during training. Learning did not transfer when the previously trained targets and nontargets switched roles or mixed up. However, learning was not specific to the trained temporal order as it transferred to trials where the motion was played backwards.These findings suggest that a demanding task of tracking multiple objects can benefit from learning of repeated motion trajectories. Such learning potentially facilitates tracking in natural vision, although learning is largely confined to the trajectories of attended objects. Furthermore, we showed that learning in attentive tracking relies on relational coding of all target trajectories. Surprisingly, learning was not specific to the trained temporal context, probably because observers have learned motion paths of each trajectory independently of the exact temporal order

Mouse allergen, lung function, and atopy in Puerto Rican children

Objective: To examine the relation between mouse allergen exposure and asthma in Puerto Rican children. Methods: Mus m 1, Der p 1, Bla g 2, and Fel d 1 allergens were measured in dust samples from homes of Puerto Rican children with (cases) and without (controls) asthma in Hartford, CT (n = 449) and San Juan (SJ), Puerto Rico (n = 678). Linear or logistic regression was used for the multivariate analysis of mouse allergen (Mus m 1) and lung function (FEV1 and FEV1/FVC) and allergy (total IgE and skin test reactivity (STR) to ≥1 allergen) measures. Results: Homes in SJ had lower mouse allergen levels than those in Hartford. In multivariate analyses, mouse allergen was associated with higher FEV1 in cases in Hartford (+70.6 ml, 95% confidence interval (CI) = 8.6-132.7 ml, P = 0.03) and SJ (+45.1 ml, 95% CI = -0.5 to 90.6 ml, P = 0.05). In multivariate analyses of controls, mouse allergen was inversely associated with STR to ≥1 allergen in non-sensitized children (odds ratio [OR] for each log-unit increment in Mus m 1 = 0.7, 95% CI = 0.5-0.9, P<0.01). In a multivariate analysis including all children at both study sites, each log-increment in mouse allergen was positively associated with FEV1 (+28.3 ml, 95% CI = 1.4-55.2 ml, P = 0.04) and inversely associated with STR to ≥1 allergen (OR for each log-unit increment in Mus m 1 = 0.8, 95% CI = 0.6-0.9, P<0.01). Conclusions: Mouse allergen is associated with a higher FEV1 and lower odds of STR to ≥1 allergen in Puerto Rican children. This may be explained by the allergen itself or correlated microbial exposures. © 2012 Forno et al

Thermodynamical Metrics and Black Hole Phase Transitions

An important phase transition in black hole thermodynamics is associated with the divergence of the specific heat with fixed charge and angular momenta, yet one can demonstrate that neither Ruppeiner's entropy metric nor Weinhold's energy metric reveals this phase transition. In this paper, we introduce a new thermodynamical metric based on the Hessian matrix of several free energy. We demonstrate, by studying various charged and rotating black holes, that the divergence of the specific heat corresponds to the curvature singularity of this new metric. We further investigate metrics on all thermodynamical potentials generated by Legendre transformations and study correspondences between curvature singularities and phase transition signals. We show in general that for a system with n-pairs of intensive/extensive variables, all thermodynamical potential metrics can be embedded into a flat (n,n)-dimensional space. We also generalize the Ruppeiner metrics and they are all conformal to the metrics constructed from the relevant thermodynamical potentials.Comment: Latex, 25 pages, reference added, typos corrected, English polished and the Hawking-Page phase transition clarified; to appear in JHE

Using internet enabled mobile devices and social networking technologies to promote exercise as an intervention for young first episode psychosis patients

<p>Abstract</p> <p>Background</p> <p>Young people with first episode psychosis are at an increased risk for a range of poor health outcomes. In contrast to the growing body of evidence that suggests that exercise therapy may benefit the physical and mental health of people diagnosed with schizophrenia, there are no studies to date that have sought to extend the use of exercise therapy among patients with first episode psychosis. The aim of the study is to test the feasibility and acceptability of an exercise program that will be delivered via internet enabled mobile devices and social networking technologies among young people with first episode psychosis.</p> <p>Methods/Design</p> <p>This study is a qualitative pilot study being conducted at Orygen Youth Health Research Centre in Melbourne, Australia. Participants are young people aged 15-24 who are receiving clinical care at a specialist first episode psychosis treatment centre. Participants will also comprise young people from the general population. The exercise intervention is a 9-week running program, designed to gradually build a person's level of fitness to be able to run 5 kilometres (3 miles) towards the end of the program. The program will be delivered via an internet enabled mobile device. Participants will be asked to post messages about their running experiences on the social networking website, and will also be asked to attend three face-to-face interviews.</p> <p>Discussion</p> <p>This paper describes the development of a qualitative study to pilot a running program coupled with the use of internet enabled mobile devices among young people with first episode psychosis. If the program is found to be feasible and acceptable to patients, it is hoped that further rigorous evaluations will ultimately lead to the introduction of exercise therapy as part of an evidence-based, multidisciplinary approach in routine clinical care.</p