Extracellular Hsp72 concentration relates to a minimum endogenous criteria during acute exercise-heat exposure

Extracellular heat-shock protein 72 (eHsp72) concentration increases during exercise-heat stress when conditions elicit physiological strain. Differences in severity of environmental and exercise stimuli have elicited varied response to stress. The present study aimed to quantify the extent of increased eHsp72 with increased exogenous heat stress, and determine related endogenous markers of strain in an exercise-heat model. Ten males cycled for 90 min at 50% O2peak in three conditions (TEMP, 20°C/63% RH; HOT, 30.2°C/51%RH; VHOT, 40.0°C/37%RH). Plasma was analysed for eHsp72 pre, immediately post and 24-h post each trial utilising a commercially available ELISA. Increased eHsp72 concentration was observed post VHOT trial (+172.4%) (P<0.05), but not TEMP (-1.9%) or HOT (+25.7%) conditions. eHsp72 returned to baseline values within 24hrs in all conditions. Changes were observed in rectal temperature (Trec), rate of Trec increase, area under the curve for Trec of 38.5°C and 39.0°C, duration Trec ≥ 38.5°C and ≥ 39.0°C, and change in muscle temperature, between VHOT, and TEMP and HOT, but not between TEMP and HOT. Each condition also elicited significantly increasing physiological strain, described by sweat rate, heart rate, physiological strain index, rating of perceived exertion and thermal sensation. Stepwise multiple regression reported rate of Trec increase and change in Trec to be predictors of increased eHsp72 concentration. Data suggests eHsp72 concentration increases once systemic temperature and sympathetic activity exceeds a minimum endogenous criteria elicited during VHOT conditions and is likely to be modulated by large, rapid changes in core temperature

Effectiveness of dry needling on reducing pain intensity in patients with myofascial pain syndrome: a Meta-analysis

AbstractObjectiveTo summarize the literature about the effectiveness of dry needling (DN) on relieving pain and increasing range of motion (ROM) in individuals with myofascial pain syndrome (MPS).MethodsPapers published from January 2000 to January 2013 were identified through an electronic search in the databases MEDLINE, Dialnet, Cochrane Library Plus, Physiotherapy Evidence Database (PEDro) and Spanish Superior Council of Scientific Research (CSIC). The studies included were randomized controlled trials written in English and/or Spanish about the effectiveness of DN on pain and ROM in individuals with MPS.ResultsOut of 19 clinical trials that were potentially relevant, a total of 10 were included in the Meta-analysis. Regarding pain intensity reduction when measured before and immediately after the intervention, DN achieved improvement compared with the placebo treatment [d = − 0.49; 95% CI (− 3.21, 0.42)] and with the control group [d = − 9.13; 95% CI (− 14.70, − 3.56)]. However, other treatments achieved better results on the same variable compared with DN, considering the measurements for pre-treatment and immediately after [d = 2.54; 95% CI (− 0.40, 5.48)], as well as the pre-treatment and after 3-4 weeks [d = 4.23; 95% CI (0.78, 7.68)]. DN showed a significantly increased ROM when measured before the intervention and immediately after, in comparison with the placebo [d = 2.00; 95% CI (1.60, 2.41)]. However, other treatments achieved a significant better result regarding ROM when it was measured before the intervention and immediately after, as compared with DN [d = −1.42; 95% CI (− 1.84, − 0.99)].ConclusionDN was less effective on decreasing pain comparing to the placebo group. Other treatments were more effective than DN on reducing pain after 3-4 weeks. However, on increasing ROM, DN was more effective comparing to that of placebo group, but less than other treatments

The Three-Dimensional Distribution of αA-Crystalline in Rat Lenses and Its Possible Relation to Transparency

Lens transparency depends on the accumulation of massive quantities (600–800 mg/ml) of twelve primary crystallines and two truncated crystallines in highly elongated “fiber” cells. Despite numerous studies, major unanswered questions are how this heterogeneous group of proteins becomes organized to bestow the lens with its unique optical properties and how it changes during cataract formation. Using novel methods based on conical tomography and labeling with antibody/gold conjugates, we have profiled the 3D-distribution of the αA-crystalline in rat lenses at ∼2 nm resolutions and three-dimensions. Analysis of tomograms calculated from lenses labeled with anti-αA-crystalline and gold particles (∼3 nm and ∼7 nm diameter) revealed geometric patterns shaped as lines, isosceles triangles and polyhedrons. A Gaussian distribution centered at ∼7.5 nm fitted the distances between the ∼3 nm diameter gold conjugates. A Gaussian distribution centered at ∼14 nm fitted the Euclidian distances between the smaller and the larger gold particles and another Gaussian at 21–24 nm the distances between the larger particles. Independent of their diameters, tethers of 14–17 nm in length connected files of gold particles to thin filaments or clusters to ∼15 nm diameter “beads.” We used the information gathered from tomograms of labeled lenses to determine the distribution of the αA-crystalline in unlabeled lenses. We found that αA-crystalline monomers spaced ∼7 nm or αA-crystalline dimers spaced ∼15 nm center-to-center apart decorated thin filaments of the lens cytoskeleton. It thus seems likely that lost or gain of long-range order determines the 3D-structure of the fiber cell and possible also cataract formation

Effect of Heterogeneous Mixing and Vaccination on the Dynamics of Anthelmintic Resistance: A Nested Model

Anthelmintic resistance is a major threat to current measures for helminth control in humans and animals. The introduction of anthelmintic vaccines, as a complement to or replacement for drug treatments, has been advocated as a preventive measure. Here, a computer-based simulation, tracking the dynamics of hosts, parasites and parasite-genes, shows that, depending on the degree of host-population mixing, the frequency of totally recessive autosomes associated with anthelmintic resistance can follow either a fast dynamical regime with a low equilibrium point or a slow dynamical regime with a high equilibrium point. For fully dominant autosomes, only one regime is predicted. The effectiveness of anthelminthic vaccines against resistance is shown to be strongly influenced by the underlying dynamics of resistant autosomes. Vaccines targeting adult parasites, by decreasing helminth fecundity or lifespan, are predicted to be more effective than vaccines targeting parasite larvae, by decreasing host susceptibility to infection, in reducing the spread of resistance. These results may inform new strategies to prevent, monitor and control the spread of anthelmintic resistance, including the development of viable anthelmintic vaccines

Intraspecies Transmission of BASE Induces Clinical Dullness and Amyotrophic Changes

The disease phenotype of bovine spongiform encephalopathy (BSE) and the molecular/ biological properties of its prion strain, including the host range and the characteristics of BSE-related disorders, have been extensively studied since its discovery in 1986. In recent years, systematic testing of the brains of cattle coming to slaughter resulted in the identification of at least two atypical forms of BSE. These emerging disorders are characterized by novel conformers of the bovine pathological prion protein (PrPTSE), named high-type (BSE-H) and low-type (BSE-L). We recently reported two Italian atypical cases with a PrPTSE type identical to BSE-L, pathologically characterized by PrP amyloid plaques and known as bovine amyloidotic spongiform encephalopathy (BASE). Several lines of evidence suggest that BASE is highly virulent and easily transmissible to a wide host range. Experimental transmission to transgenic mice overexpressing bovine PrP (Tgbov XV) suggested that BASE is caused by a prion strain distinct from the BSE isolate. In the present study, we experimentally infected Friesian and Alpine brown cattle with Italian BSE and BASE isolates via the intracerebral route. BASE-infected cattle developed amyotrophic changes accompanied by mental dullness. The molecular and neuropathological profiles, including PrP deposition pattern, closely matched those observed in the original cases. This study provides clear evidence of BASE as a distinct prion isolate and discloses a novel disease phenotype in cattle

The impact of submaximal exercise during heat and/or hypoxia on the cardiovascular and monocyte HSP72 responses to subsequent (post 24 h) exercise in hypoxia

BACKGROUND: The aims of this study were to describe the cellular stress response to prolonged endurance exercise in acute heat, hypoxia and the combination of heat and hypoxia and to determine whether prior acute exposure to these stressors improved cellular tolerance to a subsequent exercise bout in hypoxia 24 h later. METHODS: Twelve males (age 22 ± 4 years, height 1.77 ± 0.05 m, mass 79 ± 12.9 kg, VO(2) max 3.57 ± 0.7 L · min(-1)) completed four trials (30-min rest, 90-min cycling at 50% normoxic VO(2) max) in normothermic normoxia (NORM; 18°C, F(I)O(2) = 0.21), heat (HEAT; 40°C, 20% RH), hypoxia (HYP; F(I)O(2) = 0.14) or a combination of heat and hypoxia (COM; 40°C, 20% RH, F(I)O(2) = 0.14) separated by at least 7 days. Twenty-four hours after each trial, participants completed a hypoxic stress test (HST; 15-min rest, 60-min cycling at 50% normoxic VO(2) max, F(I)O(2) = 0.14). Monocyte heat shock protein 72 (mHSP72) was assessed immediately before and after each exercise bout. RESULTS: mHSP72 increased post exercise in NORM (107% ± 5.5%, p > 0.05), HYP (126% ± 16%, p < 0.01), HEAT (153% ± 14%, p < 0.01) and COM (161% ± 32%, p < 0.01). mHSP72 had returned to near-resting values 24 h after NORM (97% ± 8.6%) but was elevated after HEAT (130% ± 19%), HYP (118% ± 17%) and COM (131% ± 19%) (p < 0.05). mHSP72 increased from baseline after HST(NORM) (118% ± 12%, p < 0.05), but did not increase further in HST(HEAT), HST(HYP) and HST(COM). CONCLUSIONS: The prior induction of mHSP72 as a result of COM, HEAT and HYP attenuated further mHSP72 induction after HST and was indicative of conferred cellular tolerance

Polymeric Micelles in Anticancer Therapy: Targeting, Imaging and Triggered Release

Micelles are colloidal particles with a size around 5–100 nm which are currently under investigation as carriers for hydrophobic drugs in anticancer therapy. Currently, five micellar formulations for anticancer therapy are under clinical evaluation, of which Genexol-PM has been FDA approved for use in patients with breast cancer. Micelle-based drug delivery, however, can be improved in different ways. Targeting ligands can be attached to the micelles which specifically recognize and bind to receptors overexpressed in tumor cells, and chelation or incorporation of imaging moieties enables tracking micelles in vivo for biodistribution studies. Moreover, pH-, thermo-, ultrasound-, or light-sensitive block copolymers allow for controlled micelle dissociation and triggered drug release. The combination of these approaches will further improve specificity and efficacy of micelle-based drug delivery and brings the development of a ‘magic bullet’ a major step forward

Studying the Underlying Event in Drell-Yan and High Transverse Momentum Jet Production at the Tevatron

We study the underlying event in proton-antiproton collisions by examining the behavior of charged particles (transverse momentum pT > 0.5 GeV/c, pseudorapidity |\eta| < 1) produced in association with large transverse momentum jets (~2.2 fb-1) or with Drell-Yan lepton-pairs (~2.7 fb-1) in the Z-boson mass region (70 < M(pair) < 110 GeV/c2) as measured by CDF at 1.96 TeV center-of-mass energy. We use the direction of the lepton-pair (in Drell-Yan production) or the leading jet (in high-pT jet production) in each event to define three regions of \eta-\phi space; toward, away, and transverse, where \phi is the azimuthal scattering angle. For Drell-Yan production (excluding the leptons) both the toward and transverse regions are very sensitive to the underlying event. In high-pT jet production the transverse region is very sensitive to the underlying event and is separated into a MAX and MIN transverse region, which helps separate the hard component (initial and final-state radiation) from the beam-beam remnant and multiple parton interaction components of the scattering. The data are corrected to the particle level to remove detector effects and are then compared with several QCD Monte-Carlo models. The goal of this analysis is to provide data that can be used to test and improve the QCD Monte-Carlo models of the underlying event that are used to simulate hadron-hadron collisions.Comment: Submitted to Phys.Rev.

Measurement of Lifetime and Decay-Width Difference in B0s -> J/psi phi Decays

We measure the mean lifetime, tau=2/(Gamma_L+Gamma_H), and the width difference, DeltaGamma=Gamma_L-Gamma_H, of the light and heavy mass eigenstates of the B0s meson, B0sL and B0sH, in B0s -> J/psi phi decays using 1.7 fb^-1 of data collected with the CDF II detector at the Fermilab Tevatron ppbar collider. Assuming CP conservation, a good approximation for the B0s system in the Standard Model, we obtain DeltaGamma = 0.076^+0.059_-0.063 (stat.) +- 0.006 (syst.) ps^-1 and tau = 1.52 +- 0.04 (stat.) +- 0.02 (syst.) ps, the most precise measurements to date. Our constraints on the weak phase and DeltaGamma are consistent with CP conservation. Dedicated to the memory of our dear friend and colleague, Michael P. Schmid