Efficacy of Posaconazole in a Murine Model of Systemic Infection by Saprochaete capitata

The fungus Saprochaete capitata causes opportunistic human infections, mainly in immunocompromised patients with hematological malignancies. The best therapy for this severe infection is still unknown. We evaluated the in vitro killing activity and the in vivo efficacy of posaconazole at 5, 10, or 20 mg/kg twice a day (BID) in a murine neutropenic model of systemic infection with S. capitata by testing a set of six clinical isolates. Posaconazole showed fungistatic activity against all of the isolates tested. The different doses of the drug, especially the highest one, showed good efficacy, measured by prolonged survival, reduction of (1-3)-β-d-glucan levels in serum, tissue burden reduction, and histopathology.     

Age-related differences in proprioceptive and visuo-proprioceptive function in relation to fine motor behaviour

Leversen et al. (PLoS One 7(6):e38830, 2012) emphasise the importance of understanding the principles of life-long development. In their study of motor control, they found a common tendency towards improved motor performance from childhood to adulthood and a subsequent deterioration. The aim of our study was to examine this issue further by investigating fine motor behaviour (tracing a model line) in 196 participants (age range 12–95 years old) in two sensory conditions—proprioceptive + visual (PV) and proprioceptive only—in both hands and in two types of movement, frontal and transversal. Regression analyses of line length and task performance speed in relation to age were conducted for the different test conditions. The best performance was found in middle age, and a quadratic function provided the best fit for most of the test conditions. The corresponding inflection points (the age at which graphical analysis showed a change in performance as a peak of maturation before decline due to ageing) showed earlier ages in the proprioceptive condition. For most types of movement analysed, performance speed was slower under the PV condition. Paired correlation analysis showed that the symmetry of precision performance between hands became stronger with age. The results provide information on age-dependent differences in proprioception based on fine motor performance. They may be of use in the design of preventive strategies for preserving proprioceptive function by reducing the risk of falls and accidents or diseases such as Parkinson’s.     

Epidemiology,pathophysiology and contemporary management of cardiogenic shock – a position statement from the Heart Failure Association of the European Society of Cardiology

Cardiogenic shock (CS) is a complex multifactorial clinical syndrome with extremely high mortality, developing as a continuum, and progressing from the initial insult (underlying cause) to the subsequent occurrence of organ failure and death. There is a large spectrum of CS presentations resulting from the interaction between an acute cardiac insult and a patient's underlying cardiac and overall medical condition. Phenotyping patients with CS may have clinical impact on management because classification would support initiation of appropriate therapies. CS management should consider appropriate organization of the health care services, and therapies must be given to the appropriately selected patients, in a timely manner, whilst avoiding iatrogenic harm. Although several consensus‐driven algorithms have been proposed, CS management remains challenging and substantial investments in research and development have not yielded proof of efficacy and safety for most of the therapies tested, and outcome in this condition remains poor. Future studies should consider the identification of the new pathophysiological targets, and high‐quality translational research should facilitate incorporation of more targeted interventions in clinical research protocols, aimed to improve individual patient outcomes. Designing outcome clinical trials in CS remains particularly challenging in this critical and very costly scenario in cardiology, but information from these trials is imperiously needed to better inform the guidelines and clinical practice. The goal of this review is to summarize the current knowledge concerning the definition, epidemiology, underlying causes, pathophysiology and management of CS based on important lessons from clinical trials and registries, with a focus on improving in‐hospital management.     

BRUGADA SYNDROME

Brugada syndrome is a rare cardiac arrhythmia characterized by electrocardiographic right bundle branch block and persistent ST-segment elevation in the right precordial leads. It is associated with ventricular fibrillation and a high risk for sudden cardiac death, predominantly in younger males with structurally normal hearts. Patients can remain asymptomatic, and electrocardiographic patterns can occur both spontaneously or after pharmacological induction. So far, several pathogenic genes have been identified as associated with the disease, but SCN5A is the most prevalent one. Two consensus reports to define the diagnostic criteria, risk stratification, and management of patients have been published in the last few years. This brief review focuses on the recent clinical diagnosis, genetic basis, and advances in pharmacological treatment of Brugada syndrome.     

Novel insights on the role of CD8+ T cells and cytotoxic responses during Helicobacter pylori infection

Helicobacter pylori chronically persists in 50% of the human population and causes serious gastric and duodenal pathologies in 15% of infected people. Research on the immune response to the infection has mainly focused on the induction of CD4+ T cell responses. Human studies emphasize the potential clinical relevance of CD8+ cytotoxic T lymphocytes, however this cell type has barely been reported in studies employing mouse or gerbil models. Traditionally characterized as an extracellular bacterium, H. pylori has been identified inside epithelial and immune cells. Similarly to other intracellular bacteria, H. pylori infection of macrophages can alter autophagy and phagosome processing. A novel animal model of H. pylori infection demonstrates for the first time the induction of cytotoxic CD8+ T cell responses in pigs and localization of intracellular H. pylori within lymphoid aggregates. Here, we discuss novel mechanisms of host-H. pylori interactions that could lead to the induction of cytotoxic responses.     

Dispersion of γ-Alumina Nano-Sized Spherical Particles in a Calamitic Liquid Crystal. Study and Optimization of the Confinement Effects

We report an experimental study on confined systems formed by butyloxybenzylidene octylaniline liquid crystal (4O.8) + γ-alumina nanoparticles. The effects of the confinement in the thermal and dielectric properties of the liquid crystal under different densities of nanoparticles is analyzed by means of high resolution Modulated Differential Scanning Calorimetry (MDSC) and broadband dielectric spectroscopy. First, a drastic depression of the N-I and SmA-N transition temperatures is observed with confinement, the more concentration of nanoparticles the deeper this depression is, driving the nematic range closer to the room temperature. An interesting experimental law is found for both transition temperatures. Second, the change in shape of the heat capacity peaks is quantified by means of the full width half maximum (FWHM). Third, the confinement does not noticeably affect the molecular dynamics. Finally, the combination of nanoparticles and the external applied electric field tends to favor the alignment of the molecules in metallic cells. All these results indicate that the confinement of liquid crystals by means of γ-alumina nanoparticles could be optimum for liquid crystal-based electrooptic devices.