Aerobic capacity and skeletal muscle function in children with asthma

Background Peripheral muscle strength and endurance are decreased in patients with chronic pulmonary diseases and seem to contribute to patients' exercise intolerance. However, the authors are not aware of any studies evaluating peripheral muscle function in children with asthma. It seems to be implied that children with asthma have lower aerobic fitness, but there are limited studies comparing the aerobic capacity of children with and without asthma. The present study aimed to evaluate muscle strength and endurance in children with persistent asthma and their association with aerobic capacity and inhaled corticosteroid consumption. Methods Forty children with mild persistent asthma (MPA) or severe persistent asthma (SPA) (N=20 each) and 20 children without asthma (control group) were evaluated. Upper (pectoralis and latissimus dorsi) and lower (quadriceps) muscle strength and endurance were assessed, and cardiopulmonary exercise testing was performed. Inhaled corticosteroid consumption during the last 6 and 24 months was also quantified. Results Children with SPA presented a reduction in peak oxygen consumption (VO(2)) (28.2 +/- 8.1 vs 34.7 +/- 6.9 ml/kg/min; p<0.01) and quadriceps endurance (43.1 +/- 6.7 vs 80.9 +/- 11.9 repetitions; p<0.05) compared with the control group, but not the MPA group (31.5 +/- 6.1 ml/kg/min and 56.7 +/- 47.7 repetitions respectively; p>0.05). Maximal upper and lower muscle strength was preserved in children with both mild and severe asthma (p>0.05). Finally, the authors observed that lower muscle endurance weakness was not associated with reductions in either peak VO(2) (r=0.22, p>0.05) or corticosteroid consumption (r=-0.31, p>0.05) in children with asthma. Conclusion The findings suggest that cardiopulmonary exercise and lower limb muscle endurance should be a priority during physical training programs for children with severe asthma.

The frequency of CD127(low) expressing CD4(+)CD25(high) T regulatory cells is inversely correlated with human T lymphotrophic virus type-1 (HTLV-1) proviral load in HTLV-1-infection and HTLV-1-associated myelopathy/tropical spastic paraparesis

Background: CD4(+)CD25(high) regulatory T (T(Reg)) cells modulate antigen-specific T cell responses, and can suppress anti-viral immunity. In HTLV-1 infection, a selective decrease in the function of T(Reg) cell mediated HTLV-1-tax inhibition of FOXP3 expression has been described. The purpose of this study was to assess the frequency and phenotype of T(Reg) cells in HTLV-1 asymptomatic carriers and in HTLV-1-associated neurological disease (HAM/TSP) patients, and to correlate with measures of T cell activation. Results: We were able to confirm that HTLV-1 drives activation, spontaneous IFN gamma production, and proliferation of CD4+ T cells. We also observed a significantly lower proportion of CTLA-4(+) T(Reg) cells (CD4(+)CD25(high) T cells) in subjects with HAM/TSP patients compared to healthy controls. Ki-67 expression was negatively correlated to the frequency of CTLA-4(+) T(Reg) cells in HAM/TSP only, although Ki-67 expression was inversely correlated with the percentage of CD127(low) T(Reg) cells in healthy control subjects. Finally, the proportion of CD127(low) T(Reg) cells correlated inversely with HTLV-1 proviral load. Conclusion: Taken together, the results suggest that T(Reg) cells may be subverted in HAM/TSP patients, which could explain the marked cellular activation, spontaneous cytokine production, and proliferation of CD4(+) T cells, in particular those expressing the CD25(high)CD127(low) phenotype. T(Reg) cells represent a potential target for therapeutic intervention for patients with HTLV-1-related neurological diseases.

Factor (NF) kappa B polymorphism is associated with heart function in patients with heart failure

Background: Cardiac remodeling is generally an adverse sign and is associated with heart failure (HF) progression. NFkB, an important transcription factor involved in many cell survival pathways, has been implicated in the remodeling process, but its role in the heart is still controversial. Recently, a promoter polymorphism associated with a lesser activation of the NFKB1 gene was also associated with Dilated Cardiomyopathy. The purpose of this study was to evaluate the association of this polymorphism with clinical and functional characteristics of heart failure patients of different etiologies. Methods: A total of 493 patients with HF and 916 individuals from a cohort of individuals from the general population were investigated. The NFKB1-94 insertion/deletion ATTG polymorphism was genotyped by High Resolution Melt discrimination. Allele and genotype frequencies were compared between groups. In addition, frequencies or mean values of different phenotypes associated with cardiovascular disease were compared between genotype groups. Finally, patients were prospectively followed-up for death incidence and genotypes for the polymorphism were compared regarding disease onset and mortality incidence in HF patients. Results: We did not find differences in genotype and allelic frequencies between cases and controls. Interestingly, we found an association between the ATTG(1)/ATTG(1) genotype with right ventricle diameter (P = 0.001), left ventricle diastolic diameter (P = 0.04), and ejection fraction (EF) (P = 0.016), being the genotype ATTG(1)/ATTG(1) more frequent in patients with EF lower than 50% (P = 0.01). Finally, we observed a significantly earlier disease onset in ATTG(1)/ATTG(1) carriers. Conclusion: There is no genotype or allelic association between the studied polymorphism and the occurrence of HF in the tested population. However, our data suggest that a diminished activation of NFKB1, previously associated with the ATTG(1)/ATTG(1) genotype, may act modulating on the onset of disease and, once the individual has HF, the genotype may modulate disease severity by increasing cardiac remodeling and function deterioration.

Aspirin Treatment of Mice Infected with Trypanosoma cruzi and Implications for the Pathogenesis of Chagas Disease

Chagas disease, caused by infection with Trypanosoma cruzi, is an important cause of cardiovascular disease. It is increasingly clear that parasite-derived prostaglandins potently modulate host response and disease progression. Here, we report that treatment of experimental T. cruzi infection (Brazil strain) beginning 5 days post infection (dpi) with aspirin (ASA) increased mortality (2-fold) and parasitemia (12-fold). However, there were no differences regarding histopathology or cardiac structure or function. Delayed treatment with ASA (20 mg/kg) beginning 60 dpi did not increase parasitemia or mortality but improved ejection fraction. ASA treatment diminished the profile of parasite-and host-derived circulating prostaglandins in infected mice. To distinguish the effects of ASA on the parasite and host bio-synthetic pathways we infected cyclooxygenase-1 (COX-1) null mice with the Brazil-strain of T. cruzi. Infected COX-1 null mice displayed a reduction in circulating levels of thromboxane (TX)A(2) and prostaglandin (PG)F(2 alpha). Parasitemia was increased in COX-1 null mice compared with parasitemia and mortality in ASA-treated infected mice indicating the effects of ASA on mortality potentially had little to do with inhibition of prostaglandin metabolism. Expression of SOCS-2 was enhanced, and TRAF6 and TNF alpha reduced, in the spleens of infected ASA-treated mice. Ablation of the initial innate response to infection may cause the increased mortality in ASA-treated mice as the host likely succumbs more quickly without the initiation of the ""cytokine storm'' during acute infection. We conclude that ASA, through both COX inhibition and other ""off-target'' effects, modulates the progression of acute and chronic Chagas disease. Thus, eicosanoids present during acute infection may act as immunomodulators aiding the transition to and maintenance of the chronic phase of the disease. A deeper understanding of the mechanism of ASA action may provide clues to the differences between host response in the acute and chronic T. cruzi infection.

Improvement in Quality of Life of An Oncological Patient by Laser Phototherapy

Objective and Background Data: Common side effects of radiotherapy (RT) to the head and neck include oral mucositis, xerostomia, and severe pain. The aim of this study is to report improvement in the quality of life of an oncological patient by laser phototherapy (LPT). Clinical Case and Laser Phototherapy Protocol: The patient, a 15-year-old girl diagnosed with mucoepidermoid carcinoma, underwent surgical excision of a tumor of the left palatomaxilla. After that, she was subjected to 35 sessions of RT (2 Gy/d). Clinical examination revealed the spread of severe ulcerations to the jugal mucosa, gums, lips, hard palate, and tongue (WHO mucositis score 3). She had difficulty in moving her tongue and she was unable to eat any solid food. Oral hygiene orientation and LPT were performed throughout all RT sessions. A continuous diode laser, 660 nm, 40 mW, 6 J/cm(2), 0.24 J per point in contact mode, with spot size of 0.04 cm(2) was used in the entire oral cavity. A high-power diode laser at 1 W, 10 sec per cm of mucositis, approximately 10 J/cm(2), was used in defocused mode only on ulcerative lesions. After the first laser irradiation session, decreases in pain and xerostomia were reported; however, a more significant improvement was seen after five sessions. At that point although the mucositis score was still 2, the patient reported that she was free of pain, and consequently a palatine plate could be made to rehabilitate the entire surgical area. Seventeen laser irradiation sessions were necessary to eliminate all oral mucositis lesions. Conclusion: Normal oral function and consequent improvements in the quality of life of this oncologic patient were observed with LPT.

uvby-beta photometry of solar twins The solar colors, model atmospheres, and the T(eff) and metallicity scales

Aims. Solar colors have been determined on the uvby-beta photometric system to test absolute solar fluxes, to examine colors predicted by model atmospheres as a function of stellar parameters (T(eff), log g, [Fe/H]), and to probe zero-points of T(eff) and metallicity scales. Methods. New uvby-beta photometry is presented for 73 solar-twin candidates. Most stars of our sample have also been observed spectroscopically to obtain accurate stellar parameters. Using the stars that most closely resemble the Sun, and complementing our data with photometry available in the literature, the solar colors on the uvby-beta system have been inferred. Our solar colors are compared with synthetic solar colors computed from absolute solar spectra and from the latest Kurucz (ATLAS9) and MARCS model atmospheres. The zero-points of different T(eff) and metallicity scales are verified and corrections are proposed. Results. Our solar colors are (b - y)(circle dot) = 0.4105 +/- 0.0015, m(1,circle dot) = 0.2122 +/- 0.0018, c(1,circle dot) = 0.3319 +/- 0.0054, and beta(circle dot) = 2.5915 +/- 0.0024. The (b - y)(circle dot) and m(1,circle dot) colors obtained from absolute spectrophotometry of the Sun agree within 3-sigma with the solar colors derived here when the photometric zero-points are determined from either the STIS HST observations of Vega or an ATLAS9 Vega model, but the c(1,circle dot) and beta(circle dot) synthetic colors inferred from absolute solar spectra agree with our solar colors only when the zero-points based on the ATLAS9 model are adopted. The Kurucz solar model provides a better fit to our observations than the MARCS model. For photometric values computed from the Kurucz models, (b - y)(circle dot) and m(1,circle dot) are in excellent agreement with our solar colors independently of the adopted zero-points, but for c(1,circle dot) and beta circle dot agreement is found only when adopting the ATLAS9 zero-points. The c(1,circle dot) color computed from both the Kurucz and MARCS models is the most discrepant, probably revealing problems either with the models or observations in the u band. The T(eff) calibration of Alonso and collaborators has the poorest performance (similar to 140 K off), while the relation of Casagrande and collaborators is the most accurate (within 10 K). We confirm that the Ramirez & Melendez uvby metallicity calibration, recommended by Arnadottir and collaborators to obtain [Fe/H] in F, G, and K dwarfs, needs a small (similar to 10%) zero-point correction to place the stars and the Sun on the same metallicity scale. Finally, we confirm that the c(1) index in solar analogs has a strong metallicity sensitivity.

A VLT/FLAMES survey for massive binaries in Westerlund 1 III. The WC9d binary W239 and implications for massive stellar evolution

Context. There is growing evidence that a treatment of binarity amongst OB stars is essential for a full theory of stellar evolution. However the binary properties of massive stars - frequency, mass ratio & orbital separation - are still poorly constrained. Aims. In order to address this shortcoming we have undertaken a multiepoch spectroscopic study of the stellar population of the young massive cluster Westerlund 1. In this paper we present an investigation into the nature of the dusty Wolf-Rayet star and candidate binary W239. Methods. To accomplish this we have utilised our spectroscopic data in conjunction with multi-year optical and near-IR photometric observations in order to search for binary signatures. Comparison of these data to synthetic non-LTE model atmosphere spectra were used to derive the fundamental properties of the WC9 primary. Results. We found W239 to have an orbital period of only similar to 5.05 days, making it one of the most compact WC binaries yet identified. Analysis of the long term near-IR lightcurve reveals a significant flare between 2004-6. We interpret this as evidence for a third massive stellar component in the system in a long period (> 6 yr), eccentric orbit, with dust production occuring at periastron leading to the flare. The presence of a near-IR excess characteristic of hot (similar to 1300 K) dust at every epoch is consistent with the expectation that the subset of persistent dust forming WC stars are short (< 1 yr) period binaries, although confirmation will require further observations. Non-LTE model atmosphere analysis of the spectrum reveals the physical properties of the WC9 component to be fully consistent with other Galactic examples. Conclusions. The simultaneous presence of both short period Wolf-Rayet binaries and cool hypergiants within Wd 1 provides compelling evidence for a bifurcation in the post-Main Sequence evolution of massive stars due to binarity. Short period O+OB binaries will evolve directly to the Wolf-Rayet phase, either due to an episode of binary mediated mass loss - likely via case A mass transfer or a contact configuration - or via chemically homogenous evolution. Conversely, long period binaries and single stars will instead undergo a red loop across the HR diagram via a cool hypergiant phase. Future analysis of the full spectroscopic dataset for Wd 1 will constrain the proportion of massive stars experiencing each pathway; hence quantifying the importance of binarity in massive stellar evolution up to and beyond supernova and the resultant production of relativistic remnants.

Populations III.1 and III.2 gamma-ray bursts: constraints on the event rate for future radio and X-ray surveys

Aims. We calculate the theoretical event rate of gamma-ray bursts (GRBs) from the collapse of massive first-generation (Population III; Pop III) stars. The Pop III GRBs could be super-energetic with the isotropic energy up to E(iso) greater than or similar to 10(55-57) erg, providing a unique probe of the high-redshift Universe. Methods. We consider both the so-called Pop III.1 stars (primordial) and Pop III.2 stars (primordial but affected by radiation from other stars). We employ a semi-analytical approach that considers inhomogeneous hydrogen reionization and chemical evolution of the intergalactic medium. Results. We show that Pop III.2 GRBs occur more than 100 times more frequently than Pop III.1 GRBs, and thus should be suitable targets for future GRB missions. Interestingly, our optimistic model predicts an event rate that is already constrained by the current radio transient searches. We expect similar to 10-10(4) radio afterglows above similar to 0.3 mJy on the sky with similar to 1 year variability and mostly without GRBs (orphans), which are detectable by ALMA, EVLA, LOFAR, and SKA, while we expect to observe maximum of N < 20 GRBs per year integrated over at z > 6 for Pop III.2 and N < 0.08 per year integrated over at z > 10 for Pop III.1 with EXIST, and N < 0.2 for Pop III.2 GRBs per year integrated over at z > 6 with Swift.

In situ delivery of bone marrow cells and mesenchymal stem cells improves cardiovascular function in hypertensive rats submitted to myocardial infarction

This work aimed to evaluate cardiac morphology/function and histological changes induced by bone marrow cells (BMCs) and cultured mesenchymal stem cells (MSCs) injected at the myocardium of spontaneously hypertensive rats (SHR) submitted to surgical coronary occlusion. Female syngeneic adult SHR, submitted (MI) or not (C) to coronary occlusion, were treated 24 h later with in situ injections of normal medium (NM), or with MSCs (MSC) or BMCs (BM) from male rats. The animals were evaluated after 1 and 30 days by echocardiography, histology of heart sections and PCR for the Y chromosome. Improved ejection fraction and reduced left ventricle infarcted area were observed in MSC rats as compared to the other experimental groups. Treated groups had significantly reduced lesion tissue score, increased capillary density and normal (not-atrophied) myocytes, as compared to NM and C groups. The survival rate was higher in C, NM and MSC groups as compared to MI and BM groups. In situ injection of both MSCs and BMCs resulted in improved cardiac morphology, in a more physiological model of myocardial infarction represented by surgical coronary occlusion of spontaneously hypertensive rats. Only treatment with MSCs, however, ameliorated left ventricle dysfunction, suggesting a positive role of these cells in heart remodeling in infarcted hypertensive subjects.

Induction of Heme Oxygenase-1 Can Halt and Even Reverse Renal Tubule-Interstitial Fibrosis

Background: The tubule-interstitial fibrosis is the hallmark of progressive renal disease and is strongly associated with inflammation of this compartment. Heme-oxygenase-1 (HO-1) is a cytoprotective molecule that has been shown to be beneficial in various models of renal injury. However, the role of HO-1 in reversing an established renal scar has not yet been addressed. Aim: We explored the ability of HO-1 to halt and reverse the establishment of fibrosis in an experimental model of chronic renal disease. Methods: Sprague-Dawley male rats were subjected to unilateral ureteral obstruction (UUO) and divided into two groups: non-treated and Hemin-treated. To study the prevention of fibrosis, animals were pre-treated with Hemin at days -2 and -1 prior to UUO. To investigate whether HO-1 could reverse established fibrosis, Hemin therapy was given at days 6 and 7 post-surgery. After 7 and/or 14 days, animals were sacrificed and blood, urine and kidney tissue samples were collected for analyses. Renal function was determined by assessing the serum creatinine, inulin clearance, proteinuria/creatininuria ratio and extent of albuminuria. Arterial blood pressure was measured and fibrosis was quantified by Picrosirius staining. Gene and protein expression of pro-inflammatory and pro-fibrotic molecules, as well as HO-1 were performed. Results: Pre-treatment with Hemin upregulated HO-1 expression and significantly reduced proteinuria, albuminuria, inflammation and pro-fibrotic protein and gene expressions in animals subjected to UUO. Interestingly, the delayed treatment with Hemin was also able to reduce renal dysfunction and to decrease the expression of pro-inflammatory molecules, all in association with significantly reduced levels of fibrosis-related molecules and collagen deposition. Finally, TGF-beta protein production was significantly lower in Hemin-treated animals. Conclusion: Treatment with Hemin was able both to prevent the progression of fibrosis and to reverse an established renal scar. Modulation of inflammation appears to be the major mechanism behind HO-1 cytoprotection.

Effects of Aflatoxin B(1) and Fumonisin B(1) on the Viability and Induction of Apoptosis in Rat Primary Hepatocytes

The present study evaluated the effect of aflatoxin B(1) (AFB(1)) and fumonisin B(1) (FB(1)) either alone, or in association, on rat primary hepatocyte cultures. Cell viability was assessed by flow cytometry after propidium iodine intercalation. DNA fragmentation and apoptosis were assessed by agarose gel electrophoresis and acridine orange and ethidium bromide staining. At the concentrations of AFB(1) and FB(1) used, the toxins did not decrease cell viability, but did induce apoptosis in a concentration and time-dependent manner.

Measurement of the underground atmospheric muon charge ratio using the MINOS Near Detector

The magnetized MINOS Near Detector, at a depth of 225 mwe, is used to measure the atmospheric muon charge ratio. The ratio of observed positive to negative atmospheric muon rates, using 301 days of data, is measured to be 1.266 +/- 0.001(stat)(-0.014)(+0.015)(syst). This measurement is consistent with previous results from other shallow underground detectors and is 0.108 +/- 0.019(stat + syst) lower than the measurement at the functionally identical MINOS Far Detector at a depth of 2070 mwe. This increase in charge ratio as a function of depth is consistent with an increase in the fraction of muons arising from kaon decay for increasing muon surface energies.

Cold Nuclear Matter Effects on J/psi Yields as a Function of Rapidity and Nuclear Geometry in d plus A Collisions at root S(NN)=200 GeV

We present measurements of J/psi yields in d + Au collisions at root S(NN) = 200 GeV recorded by the PHENIX experiment and compare them with yields in p + p collisions at the same energy per nucleon-nucleon collision. The measurements cover a large kinematic range in J/psi rapidity (-2.2 < y < 2.4) with high statistical precision and are compared with two theoretical models: one with nuclear shadowing combined with final state breakup and one with coherent gluon saturation effects. In order to remove model dependent systematic uncertainties we also compare the data to a simple geometric model. The forward rapidity data are inconsistent with nuclear modifications that are linear or exponential in the density weighted longitudinal thickness, such as those from the final state breakup of the bound state.

Nuclear modification factors of phi mesons in d plus Au, Cu plus Cu, and Au plus Au collisions at root s(NN)=200 GeV

The PHENIX experiment at the Relativistic Heavy Ion Collider has performed systematic measurements of phi meson production in the K(+)K(-) decay channel at midrapidity in p + p, d + Au, Cu + Cu, and Au + Au collisions at root s(NN) = 200 GeV. Results are presented on the phi invariant yield and the nuclear modification factor R(AA) for Au + Au and Cu + Cu, and R(dA) for d + Au collisions, studied as a function of transverse momentum (1 < p(T) < 7 GeV/c) and centrality. In central and midcentral Au + Au collisions, the R(AA) of phi exhibits a suppression relative to expectations from binary scaled p + p results. The amount of suppression is smaller than that of the pi(0) and the. in the intermediate p(T) range (2-5 GeV/c), whereas, at higher p(T), the phi, pi(0), and. show similar suppression. The baryon (proton and antiproton) excess observed in central Au + Au collisions at intermediate p(T) is not observed for the phi meson despite the similar masses of the proton and the phi. This suggests that the excess is linked to the number of valence quarks in the hadron rather than its mass. The difference gradually disappears with decreasing centrality, and, for peripheral collisions, the R(AA) values for both particle species are consistent with binary scaling. Cu + Cu collisions show the same yield and suppression as Au + Au collisions for the same number of N(part). The R(dA) of phi shows no evidence for cold nuclear effects within uncertainties.

Cross Section and Parity-Violating Spin Asymmetries of W(+/-) Boson Production in Polarized p plus p Collisions at root s=500 Gev

Large parity-violating longitudinal single-spin asymmetries A(L)(e+) = 0.86(-0.14)(+0.30) and Ae(L)(e-) = 0.88(-0.71)(+0.12) are observed for inclusive high transverse momentum electrons and positrons in polarized p + p collisions at a center-of-mass energy of root s = 500 GeV with the PHENIX detector at RHIC. These e(+/-) come mainly from the decay of W(+/-) and Z(0) bosons, and their asymmetries directly demonstrate parity violation in the couplings of the W(+/-) to the light quarks. The observed electron and positron yields were used to estimate W(+/-) boson production cross sections for the e(+/-) channels of sigma(pp -> W(+)X) X BR(W(+) -> e(+) nu(e)) = 144.1 +/- 21.2(stat)(-10.3)(+3.4)(syst) +/- 21.6(norm) pb, and sigma(pp -> W(-)X) X BR(W(-) -> e(-) (nu) over bar (e)) = 3.17 +/- 12.1(stat)(-8.2)(+10.1)(syst) +/- 4.8(norm) pb.