β-adrenergic inhibition prevents action potential and calcium handling changes during regional myocardial ischemia

β-adrenergic receptor (β-AR) blockers may be administered during acute myocardial infarction (MI), as they reduce energy demand through negative chronotropic and inotropic effects and prevent ischemia-induced arrhythmogenesis. However, the direct effects of β-AR blockers on ventricular electrophysiology and intracellular Ca2+ handling during ischemia remain unknown. Using optical mapping of transmembrane potential (with RH237) and sarcoplasmic reticulum (SR) Ca2+ (with the low-affinity indicator Fluo-5N AM), the effects of 15 min of regional ischemia were assessed in isolated rabbit hearts (n = 19). The impact of β-AR inhibition on isolated hearts was assessed by pre-treatment with 100 nM propranolol (Prop) prior to ischemia (n = 7). To control for chronotropy and inotropy, hearts were continuously paced at 3.3 Hz and contraction was inhibited with 20 μM blebbistatin. Untreated ischemic hearts displayed prototypical shortening of action potential duration (APD80) in the ischemic zone (IZ) compared to the non-ischemic zone (NI) at 10 and 15 min ischemia, whereas APD shortening was prevented with Prop. Untreated ischemic hearts also displayed significant changes in SR Ca2+ handling in the IZ, including prolongation of SR Ca2+ reuptake and SR Ca2+ alternans, which were prevented with Prop pre-treatment. At 5 min ischemia, Prop pre-treated hearts also showed larger SR Ca2+ release amplitude in the IZ compared to untreated hearts. These results suggest that even when controlling for chronotropic and inotropic effects, β-AR inhibition has a favorable effect during acute regional ischemia via direct effects on APD and Ca2+ handling

Incidence and predictors of immediate complications following perioperative non-obstetric epidural punctures

Background: Epidural Anesthesia (EA) is a well-established procedure. The aim of the present study was to evaluate the incidence of immediate complications following epidural puncture, such as sanguineous puncture, accidental dural perforation, unsuccessful catheter placement or insufficient analgesia and to identify patient and maneuver related risk factors. Methods: A total of 7958 non-obstetrical EA were analyzed. The risk of each complication was calculated according to the preconditions and the level of puncture. For probabilistic evaluation we used a logistic regression model with forward selection. Results: The risk of sanguineous puncture (n = 247, 3.1%) increases with both the patient's age (P = 0.013) and the more caudal the approach (P &lt; 0.01). Dural perforation (n = 123, 1.6%) was found to be influenced only by advanced age (P = 0.019). Unsuccessful catheter placement (n = 68, 0.94%) occurred more often in smaller individuals (P < 0.001) and at lower lumbar sites (P < 0.01). Amongst all cases with successful catheter placement a (partial) insufficient analgesia was found in 692 cases (8.8%). This risk of insufficient analgesia decreased with patient's age (P < 0.01), being least likely for punctures of the lower thoracic spine (P < 0.001). Conclusions: Compared to more cranial levels, EA of the lower spine is associated with an increased risk of sanguineous and unsuccessful puncture. Insufficient analgesia more often accompanies high thoracic and low lumbar approaches. The risk of a sanguineous puncture increases in elderly patients. Gender, weight and body mass index seem to have no influence on the investigated complications

Incidence and predictors of immediate complications following perioperative non-obstetric epidural punctures

Background: Epidural Anesthesia (EA) is a well-established procedure. The aim of the present study was to evaluate the incidence of immediate complications following epidural puncture, such as sanguineous puncture, accidental dural perforation, unsuccessful catheter placement or insufficient analgesia and to identify patient and maneuver related risk factors. Methods: A total of 7958 non-obstetrical EA were analyzed. The risk of each complication was calculated according to the preconditions and the level of puncture. For probabilistic evaluation we used a logistic regression model with forward selection. Results: The risk of sanguineous puncture (n = 247, 3.1%) increases with both the patient's age (P = 0.013) and the more caudal the approach (P &lt; 0.01). Dural perforation (n = 123, 1.6%) was found to be influenced only by advanced age (P = 0.019). Unsuccessful catheter placement (n = 68, 0.94%) occurred more often in smaller individuals (P < 0.001) and at lower lumbar sites (P < 0.01). Amongst all cases with successful catheter placement a (partial) insufficient analgesia was found in 692 cases (8.8%). This risk of insufficient analgesia decreased with patient's age (P < 0.01), being least likely for punctures of the lower thoracic spine (P < 0.001). Conclusions: Compared to more cranial levels, EA of the lower spine is associated with an increased risk of sanguineous and unsuccessful puncture. Insufficient analgesia more often accompanies high thoracic and low lumbar approaches. The risk of a sanguineous puncture increases in elderly patients. Gender, weight and body mass index seem to have no influence on the investigated complications

On the Perceptual Organization of Speech

A general account of auditory perceptual organization has developed in the past 2 decades. It relies on primitive devices akin to the Gestalt principles of organization to assign sensory elements to probable groupings and invokes secondary schematic processes to confirm or to repair the possible organization. Although this conceptualization is intended to apply universally, the variety and arrangement of acoustic constituents of speech violate Gestalt principles at numerous junctures, cohering perceptually, nonetheless. The authors report 3 experiments on organization in phonetic perception, using sine wave synthesis to evade the Gestalt rules and the schematic processes alike. These findings falsify a general auditory account, showing that phonetic perceptual organization is achieved by specific sensitivity to the acoustic modulations characteristic of speech signals

Prospective, randomized, double-blind trial to investigate the efficacy and safety of corneal cross-linking to halt the progression of keratoconus

Background: Corneal cross-linking is widely used to treat keratoconus. However, to date, only limited data from randomized trials support its efficacy. Methods: The efficacy and safety of corneal cross-linking for halting progression of keratoconus were investigated in a prospective, randomized, blinded, placebo controlled, multicentre trial. Twenty-nine keratoconus patients were randomized in three trial centres. The mean age at inclusion was 28 years. Longitudinal changes in corneal refraction were assessed by linear regression. The best corrected visual acuity, surface defects and corneal inflammation were also assessed. These data were analysed with a multifactorial linear regression model. Results: A total of 15 eyes were randomized to the treatment and 14 to the control group. Follow-up averaged 1098 days. Corneal refractive power decreased on average (+/-standard deviation) by 0.35 +/- 0.58 dioptres/year in the treatment group. The controls showed an increase of 0.11 +/- 0.61 dioptres/year. This difference was statistically significant (p = 0.02). Conclusions: Our data suggest that corneal cross-linking is an effective treatment for some patients to halt the progression of keratoconus. However, some of the treated patients still progressed, whereas some untreated controls improved. Therefore, further investigations are necessary to decide which patients require treatment and which do not

Sustainable Diets: another hurdle or a better food future?,

The notion of sustainable diets has emerged forcibly onto the food policy agenda in recent years, but has also met resistance. The article reviews the case for sustainable diets. It counterbalances the current dominant policy emphasis on raising food output as the best route to a sustainable food future. The article suggests that a process of democratic experimentation is underway. Some official guidelines have emerged alongside a mix of civil society and academic formulations. More coherence of data, principles and purpose is needed at the global and regional policy-making levels for these to become effective in the common task of reducing the food system’s negative impact on health, environment and economies

The Panchromatic Hubble Andromeda Treasury I: Bright UV Stars in the Bulge of M31

As part of the Panchromatic Hubble Andromeda Treasury (PHAT) multi-cycle program, we observed a 12' \times 6.5' area of the bulge of M31 with the WFC3/UVIS filters F275W and F336W. From these data we have assembled a sample of \sim4000 UV-bright, old stars, vastly larger than previously available. We use updated Padova stellar evolutionary tracks to classify these hot stars into three classes: Post-AGB stars (P-AGB), Post-Early AGB (PE-AGB) stars and AGB-manqu\'e stars. P-AGB stars are the end result of the asymptotic giant branch (AGB) phase and are expected in a wide range of stellar populations, whereas PE-AGB and AGB-manqu\'e (together referred to as the hot post-horizontal branch; HP-HB) stars are the result of insufficient envelope masses to allow a full AGB phase, and are expected to be particularly prominent at high helium or {\alpha} abundances when the mass loss on the RGB is high. Our data support previous claims that most UV-bright sources in the bulge are likely hot (extreme) horizontal branch stars (EHB) and their progeny. We construct the first radial profiles of these stellar populations, and show that they are highly centrally concentrated, even more so than the integrated UV or optical light. However, we find that this UV-bright population does not dominate the total UV luminosity at any radius, as we are detecting only the progeny of the EHB stars that are the likely source of the UVX. We calculate that only a few percent of MS stars in the central bulge can have gone through the HP-HB phase and that this percentage decreases strongly with distance from the center. We also find that the surface density of hot UV-bright stars has the same radial variation as that of low-mass X-ray binaries. We discuss age, metallicity, and abundance variations as possible explanations for the observed radial variation in the UV-bright population.Comment: Accepted for publication in Ap

The bidirectional tumor - mesenchymal stromal cell interaction promotes the progression of head and neck cancer

Introduction: Mesenchymal stromal cells (MSC) are an integral cellular component of the tumor microenvironment. Nevertheless, very little is known about MSC originating from human malignant tissue and modulation of these cells by tumor-derived factors. The aim of this study was to isolate and characterize MSC from head and neck squamous cell carcinoma (HNSCC) and to investigate their interaction with tumor cells. Methods: MSC were isolated from tumor tissues of HNSCC patients during routine oncological surgery. Immunophenotyping, immunofluorescence and in vitro differentiation were performed to determine whether the isolated cells met the consensus criteria for MSC. The cytokine profile of tumor-derived MSC was determined by enzyme-linked immunosorbent assay (ELISA). Activation of MSC by tumor-conditioned media was assessed by measuring cytokine release and expression of CD54. The impact of MSC on tumor growth in vivo was analyzed in a HNSCC xenograft model. Results: Cells isolated from HNSCC tissue met the consensus criteria for MSC. Tumor-derived MSC constitutively produced high amounts of interleukin (IL)-6, IL-8 and stromal cell-derived factor (SDF)-1α. HNSCC-derived factors activated MSC and enhanced secretion of IL-8 and expression of CD54. Furthermore, MSC provided stromal support for human HNSCC cell lines in vivo and enhanced their growth in a murine xenograft model. Conclusions: This is the first study to isolate and characterize MSC from malignant tissues of patients with HNSCC. We observed cross-talk of stromal cells and tumor cells resulting in enhanced growth of HNSCC in vivo