Does impaired O-2 delivery during exercise accentuate central and peripheral fatigue in patients with coexistent COPD-CHF?

Impairment in oxygen (O-2) delivery to the central nervous system (brain) and skeletal locomotor muscle during exercise has been associated with central and peripheral neuromuscular fatigue in healthy humans. From a clinical perspective, impaired tissue O-2 transport is a key pathophysiological mechanism shared by cardiopulmonary diseases, such as chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF). in addition to arterial hypoxemic conditions in COPD, there is growing evidence that cerebral and muscle blood flow and oxygenation can be reduced during exercise in both isolated COPD and CHF. Compromised cardiac output due to impaired cardiopulmonary function/interactions and blood flow redistribution to the overloaded respiratory muscles (i.e., up arrow work of breathing) may underpin these abnormalities. Unfortunately, COPD and CHF coexist in almost a third of elderly patients making these mechanisms potentially more relevant to exercise intolerance. in this context, it remains unknown whether decreased O-2 delivery accentuates neuromuscular manifestations of central and peripheral fatigue in coexistent COPD-CHF If this holds true, it is conceivable that delivering a low-density gas mixture (heliox) through non-invasive positive pressure ventilation could ameliorate cardiopulmonary function/interactions and reduce the work of breathing during exercise in these patients. the major consequence would be increased O-2 delivery to the brain and active muscles with potential benefits to exercise capacity (i.e.,,central and peripheral neuromuscular fatigue, respectively). We therefore hypothesize that patients with coexistent COPD-CHF stop exercising prematurely due to impaired central motor drive and muscle contractility as the cardiorespiratory system fails to deliver sufficient O-2 to simultaneously attend the metabolic demands of the brain and the active limb muscles.Universidade Federal de São Paulo, Dept Med, Pulm Funct & Clin Exercise Physiol Unit SEFICE, Resp Div,Sch Med,UNIFESP, São Paulo, BrazilQueens Univ, Dept Med, Lab Clin Exercise Physiol, Div Resp & Crit Care Med, Kingston, ON K7L 3N6, CanadaQueens Univ, Dept Med, Resp Invest Unit, Div Resp & Crit Care Med, Kingston, ON K7L 3N6, CanadaGrenoble Alpes Univ, Lab HP2, Grenoble, FranceUniversidade Federal de São Paulo, Dept Med, Pulm Funct & Clin Exercise Physiol Unit SEFICE, Resp Div,Sch Med,UNIFESP, São Paulo, BrazilWeb of Scienc

The effects of dietary fish oil on exercising skeletal muscle vascular and metabolic control in chronic heart failure rats

The ATP-sensitive K+ (KATP) channel is a class of inward rectifier K+ channels that can link cellular metabolic status to vasomotor tone across the metabolic transients seen with exercise. This investigation tested the hypothesis that if KATP channels are crucial to exercise hyperaemia then blockade via glibenclamide (GLI) would lower hindlimb skeletal muscle blood flow (BF) and vascular conductance (VC) during treadmill exercise. In 14 adult male Sprague Dawley rats mean arterial pressure (MAP), blood [lactate], and hindlimb muscle BF (radiolabelled microspheres) were determined at rest (n = 6) or during exercise (n = 8; 20 m min⁻¹, 5% incline) under control (CON) and GLI conditions (5 mg kg⁻¹, i.a). At rest and during exercise, MAP was higher (Rest, CON: 130 ± 6, GLI: 152 ± 8; Exercise, CON: 140 ± 4, GLI: 147 ± 4 mmHg, P < 0.05) and heart rate (HR) was lower (Rest, CON: 440 ± 16, GLI: 410 ± 18; Exercise, CON: 560 ± 4, GLI: 540 ± 10 beats min⁻¹, P < 0.05) with GLI. Hindlimb muscle BF (CON: 144 ± 10, GLI: 120 ± 9 ml min⁻¹ (100 g)⁻¹, P < 0.05) and VC were lower with GLI during exercise but not at rest. Specifically, GLI decreased BF in 12, and VC in 16, of the 28 individual hindlimb muscles and muscle parts sampled during exercise with a greater fractional reduction present in muscles comprised predominantly of type I and type IIa fibres (P < 0.05). Additionally, blood [lactate] (CON: 2.0 ± 0.3; GLI: 4.1 ± 0.9 mmol L⁻¹, P < 0.05) was higher during exercise with GLI. That KATP channel blockade reduces hindlimb muscle BF during exercise in rats supports the obligatory contribution of KATP channels in large muscle mass exercise-induced hyperaemia

Cyclic AMP Responsive Element Binding Proteins Are Involved in ‘Emergency’ Granulopoiesis through the Upregulation of CCAAT/Enhancer Binding Protein β

In contrast to the definitive role of the transcription factor, CCAAT/Enhancer binding protein α (C/EBPα), in steady-state granulopoiesis, previous findings have suggested that granulopoiesis during emergency situations, such as infection, is dependent on C/EBPβ. In this study, a novel lentivirus-based reporter system was developed to elucidate the molecular switch required for C/EBPβ-dependency. The results demonstrated that two cyclic AMP responsive elements (CREs) in the proximal promoter region of C/EBPβ were involved in the positive regulation of C/EBPβ transcription during granulocyte-macrophage colony-stimulating factor (GM-CSF)–induced differentiation of bone marrow cells. In addition, the transcripts of CRE binding (CREB) family proteins were readily detected in hematopoietic stem/progenitor cells. CREB was upregulated, phosphorylated and bound to the CREs in response to GM-CSF stimulation. Retroviral transduction of a dominant negative CREB mutant reduced C/EBPβ mRNA levels and significantly impaired the proliferation/differentiation of granulocyte precursors, while a constitutively active form of CREB facilitated C/EBPβ transcription. These data suggest that CREB proteins are involved in the regulation of granulopoiesis via C/EBPβ upregulation

Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes.

A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM-receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes, including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). There is some evidence that these ECM cues affect one or more of the following processes: cell survival, polarity, proliferation, differentiation, adhesion, and migration. Both three-dimensional culture models and genetic manipulations of the mouse mammary gland have been used to study the signaling pathways that affect these processes. However, the precise mechanisms of ECM-directed mammary morphogenesis are not well understood. Mammary morphogenesis involves epithelial 'invasion' of adipose tissue, a process akin to invasion by breast cancer cells, although the former is a highly regulated developmental process. How these morphogenic pathways are integrated in the normal gland and how they become dysregulated and subverted in the progression of breast cancer also remain largely unanswered questions

Multifocus HDR VIS/NIR hyperspectral imaging and its application to works of art

The authors would like to thank Mr. Francisco Fernández Fábregas, owner of the Transfiguration of Christ for allowing us the privilege of studying this painting. We also acknowledge the collaboration of Angela Tate.This paper presents a complete framework for capturing and processing hyperspectral reflectance images of artworks in situ, using a hyperspectral line scanner. These capturing systems are commonly used in laboratory conditions synchronized with scanning stages specifically designed for planar surfaces. However, when the intended application domain does not allow for image capture in these controlled conditions, achieving useful spectral reflectance image data can be a very challenging task (due to uncontrolled illumination, high-dynamic range (HDR) conditions in the scene, and the influence of chromatic aberration on the image quality, among other factors). We show, for the first time, all the necessary steps in the image capturing and post-processing in order to obtain high-quality HDR-based reflectance in the visible and near infrared, directly from the data captured by using a hyperspectral line scanner coupled to a rotating tripod. Our results show that the proposed method outperforms the normal capturing process in terms of dynamic range, color and spectral accuracy. To demonstrate the potential interest of this processing strategy for on-site analysis of artworks, we applied it to the study of a vintage copy of the famous painting “Transfiguration” by Raphael, as well as a facsimile of “The Golden Haggadah” from the British Library of London. The second piece has been studied for the identification of highly reflective gold-foil covered areas.Spanish Ministry of Economy and Competitiveness, DPI2015-64571-R, ECQM2018-004952-

Precise Measurements of Beam Spin Asymmetries in Semi-Inclusive π0\pi^0 production

We present studies of single-spin asymmetries for neutral pion electroproduction in semi-inclusive deep-inelastic scattering of 5.776 GeV polarized electrons from an unpolarized hydrogen target, using the CEBAF Large Acceptance Spectrometer (CLAS) at the Thomas Jefferson National Accelerator Facility. A substantial $\sin \phi_h$ amplitude has been measured in the distribution of the cross section asymmetry as a function of the azimuthal angle $\phi_h$ of the produced neutral pion. The dependence of this amplitude on Bjorken $x$ and on the pion transverse momentum is extracted with significantly higher precision than previous data and is compared to model calculations.Comment: to be submitted PL

Multidrug-resistant Acinetobacter Infection Mortality Rate and Length of Hospitalization

Acinetobacter infections have increased and gained attention because of the organism’s prolonged environmental survival and propensity to develop antimicrobial drug resistance. The effect of multidrug-resistant (MDR) Acinetobacter infection on clinical outcomes has not been reported. A retrospective, matched cohort investigation was performed at 2 Baltimore hospitals to examine outcomes of patients with MDR Acinetobacter infection compared with patients with susceptible Acinetobacter infections and patients without Acinetobacter infections. Multivariable analysis controlling for severity of illness and underlying disease identified an independent association between patients with MDR Acinetobacter infection (n = 96) and increased hospital and intensive care unit length of stay compared with 91 patients with susceptible Acinetobacter infection (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.2–5.2 and OR 2.1, 95% CI 1.0–4.3] respectively) and 89 uninfected patients (OR 2.5, 95% CI 1.2–5.4 and OR 4.2, 95% CI 1.5–11.6] respectively). Increased hospitalization associated with MDR Acinetobacter infection emphasizes the need for infection control strategies to prevent cross-transmission in healthcare settings