Efficacy of pimobendan in the prevention of congestive heart failure or sudden death in doberman pinschers with preclinical dilated cardiomyopathy (the PROTECT study)

<p>Background: The benefit of pimobendan in delaying the progression of preclinical dilated cardiomyopathy (DCM) in Dobermans is not reported.</p> <p>Hypothesis: That chronic oral administration of pimobendan to Dobermans with preclinical DCM will delay the onset of CHF or sudden death and improve survival.</p> <p>Animals: Seventy-six client-owned Dobermans recruited at 10 centers in the UK and North America.</p> <p>Methods: The trial was a randomized, blinded, placebo-controlled, parallel group multicenter study. Dogs were allocated in a 1:1 ratio to receive pimobendan (Vetmedin capsules) or visually identical placebo.</p> <p>The composite primary endpoint was prospectively defined as either onset of CHF or sudden death. Time to death from all causes was a secondary endpoint.</p> <p>Results: The proportion of dogs reaching the primary endpoint was not significantly different between groups (P = .1). The median time to the primary endpoint (onset of CHF or sudden death) was significantly longer in the pimobendan (718 days, IQR 441–1152 days) versus the placebo group (441 days, IQR 151–641 days) (log-rank P = 0.0088). The median survival time was significantly longer in the pimobendan (623 days, IQR 491–1531 days) versus the placebo group (466 days, IQR 236–710 days) (log-rank P = .034).</p> <p>Conclusion and Clinical Importance: The administration of pimobendan to Dobermans with preclinical DCM prolongs the time to the onset of clinical signs and extends survival. Treatment of dogs in the preclinical phase of this common cardiovascular disorder with pimobendan can lead to improved outcome.</p&gt

Effect of dietary changes on the bacteriophage population in the rumen of sheep

Item does not contain fulltext4th Symposium on Gut Microbiology, 21 juni 200

Resonantly damped surface and body MHD waves in a solar coronal slab with oblique propagation

The theory of magnetohydrodynamic (MHD) waves in solar coronal slabs in a zero-$\beta$ configuration and for parallel propagation of waves does not allow the existence of surface waves. When oblique propagation of perturbations is considered both surface and body waves are able to propagate. When the perpendicular wave number is larger than a certain value, the body kink mode becomes a surface wave. In addition, a sausage surface mode is found below the internal cut-off frequency. When non-uniformity in the equilibrium is included, surface and body modes are damped due to resonant absorption. In this paper, first, a normal-mode analysis is performed and the period, the damping rate, and the spatial structure of eigenfunctions are obtained. Then, the time-dependent problem is solved, and the conditions under which one or the other type of mode is excited are investigated.Comment: 19 pages, 9 figures, accepted for publication in Solar Physic

La estrategia Educativa 2020 o las limitaciones del Banco Mundial para promover el "aprendizaje para todos"

La nueva Estrategia Educativa 2020 del Banco Mundial establece las prioridades de reforma educativa en paises en vias de desarrollo para la decada siguiente. El titulo explicito de la estrategia, Aprendizaje para Todos, es un claro reconocimiento de que, mas alla de politicas centradas en el acceso, se debe hacer algo mas para asegurar que la educacion derive en experiencias positivas de aprendizaje. Sin embargo, como este articulo sostiene, las opciones de politicas explicitas y latentes en la Estrategia 2020 no son las mas adecuadas para lograr el Aprendizaje para Todos. El articulo desarrolla tres tipos de argumentos al respecto. El primero se refiere al fuerte apego del Banco a un conocimiento disciplinario y un enfoque metodológico que es insufi ciente para entender lo que aprenden los niños en la escuela y por que. El segundo argumento se refiere al sesgo pro-mercado de la Estrategia por lo que respecta a la reforma del sector publico y a nuevas formas de oferta educativa. En tercer lugar, el articulo senala las principales ausencias de la Estrategia, con especial atencion a las omisiones relacionadas con la compleja relación entre educación y pobreza.The World Bank's 2020 Education Strategy establishes the new education priorities in developing countries for the next decade. Its title, Learning for All, clearly recognizes that, beyond policies focusing on access, something else must be done to ensure that schooling involves positive learning experiences. However, as this paper argues, the 2020 Strategy explicit and latent policy options might not be adequate to achieve Learning for All. This paper develops three arguments on that matter. The fi rst one refers to the Bank's strong attachment to a disciplinary knowledge and a methodological approach that do not suffi ce to understand what children learn at school and why. The second one addresses its pro-market bias when it approaches the public sector reforms and the new forms of providing education. The last argument points out the main omissions of this Strategy, especially in what regards the complex relation between education and poverty

Chemical synergy between ionophore PBT2 and zinc reverses antibiotic resistance

The World Health Organization reports that antibiotic-resistant pathogens represent an imminent global health disaster for the 21st century. Gram-positive superbugs threaten to breach last-line antibiotic treatment, and the pharmaceutical industry antibiotic development pipeline is waning. Here we report the synergy between ionophore-induced physiological stress in Gram-positive bacteria and antibiotic treatment. PBT2 is a safe-for-human-use zinc ionophore that has progressed to phase 2 clinical trials for Alzheimer's and Huntington's disease treatment. In combination with zinc, PBT2 exhibits antibacterial activity and disrupts cellular homeostasis in erythromycin-resistant group A Streptococcus (GAS), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE). We were unable to select for mutants resistant to PBT2-zinc treatment. While ineffective alone against resistant bacteria, several clinically relevant antibiotics act synergistically with PBT2-zinc to enhance killing of these Gram-positive pathogens. These data represent a new paradigm whereby disruption of bacterial metal homeostasis reverses antibiotic-resistant phenotypes in a number of priority human bacterial pathogens.IMPORTANCE The rise of bacterial antibiotic resistance coupled with a reduction in new antibiotic development has placed significant burdens on global health care. Resistant bacterial pathogens such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus are leading causes of community- and hospital-acquired infection and present a significant clinical challenge. These pathogens have acquired resistance to broad classes of antimicrobials. Furthermore, Streptococcus pyogenes, a significant disease agent among Indigenous Australians, has now acquired resistance to several antibiotic classes. With a rise in antibiotic resistance and reduction in new antibiotic discovery, it is imperative to investigate alternative therapeutic regimens that complement the use of current antibiotic treatment strategies. As stated by the WHO Director-General, "On current trends, common diseases may become untreatable. Doctors facing patients will have to say, Sorry, there is nothing I can do for you."Lisa Bohlmann, David M. P. De Oliveira, Ibrahim M. El-Deeb, Erin B. Brazel, Nichaela Harbison-Pric

Rescuing tetracycline class antibiotics for the treatment of multidrug-resistant Acinetobacter baumannii pulmonary infection

Acinetobacter baumannii causes high mortality in ventilator-associated pneumonia patients, and antibiotic treatment is compromised by multidrug-resistant strains resistant to β-lactams, carbapenems, cephalosporins, polymyxins, and tetracyclines. Among COVID-19 patients receiving ventilator support, a multidrug-resistant A. baumannii secondary infection is associated with a 2-fold increase in mortality. Here, we investigated the use of the 8-hydroxyquinoline ionophore PBT2 to break the resistance of A. baumannii to tetracycline class antibiotics. In vitro, the combination of PBT2 and zinc with either tetracycline, doxycycline, or tigecycline was shown to be bactericidal against multidrug-resistant A. baumannii, and any resistance that did arise imposed a fitness cost. PBT2 and zinc disrupted metal ion homeostasis in A. baumannii, increasing cellular zinc and copper while decreasing magnesium accumulation. Using a murine model of pulmonary infection, treatment with PBT2 in combination with tetracycline or tigecycline proved efficacious against multidrug-resistant A. baumannii. These findings suggest that PBT2 may find utility as a resistance breaker to rescue the efficacy of tetracycline-class antibiotics commonly employed to treat multidrug-resistant A. baumannii infections. Importance: Within intensive care unit settings, multidrug-resistant (MDR) Acinetobacter baumannii is a major cause of ventilator-associated pneumonia, and hospital-associated outbreaks are becoming increasingly widespread. Antibiotic treatment of A. baumannii infection is often compromised by MDR strains resistant to last-resort β-lactam (e.g., carbapenems), polymyxin, and tetracycline class antibiotics. During the on-going COVID-19 pandemic, secondary bacterial infection by A. baumannii has been associated with a 2-fold increase in COVID-19-related mortality. With a rise in antibiotic resistance and a reduction in new antibiotic discovery, it is imperative to investigate alternative therapeutic regimens that complement the use of current antibiotic treatment strategies. Rescuing the efficacy of existing therapies for the treatment of MDR A. baumannii infection represents a financially viable pathway, reducing time, cost, and risk associated with drug innovation.David M.P. De Oliveira, Brian M. Forde, Minh-Duy Phan, Bernhard Steiner, Bing Zhang, Johannes Zuegg, Ibrahim M. El-deeb, Gen Li, Nadia Keller, Stephan Brouwer, Nichaela Harbison-Price, Amanda J. Cork, Michelle J. Bauer, Saleh F. Alquethamy, Scott A. Beatson, Jason A. Roberts, David L. Paterson, Alastair G. McEwan, Mark A.T. Blaskovich, Mark A. Schembri, Christopher A. McDevitt, Mark von Itzstein, Mark J. Walke

Wireless Electromagnetic Radiation Assessment Based on the Specific Absorption Rate (SAR): A Review Case Study

Employing Electromagnetic Fields (EMFs) in new wireless communication and sensing technologies has substantially increased the level of human exposure to EMF waves. This paper presents a useful insight into the interaction of electromagnetic fields with biological media that is defined by the heat generation due to induced currents and dielectric loss. The Specific Absorption Rate (SAR) defines the heating amount in a biological medium that is irradiated by an electromagnetic field value. The paper reviews the radio frequency hazards due to the SAR based on various safety standards and organisations, including a detailed investigation of previously published work in terms of modelling and measurements. It also summarizes the most common techniques utilised between 1978 and 2021, in terms of the operational frequency spectrum, bandwidth, and SAR values