Impact of Thoracoscopic Pulmonary Vein Isolation on Right Ventricular Function:A Pilot Study

Objective. Thoracoscopic surgical pulmonary vein isolation (sPVI) has been added to the treatment of atrial fibrillation (AF), showing excellent efficacy outcomes. However, data on right ventricular (RV) function following sPVI has never been studied. Our aim was to investigate RV function following sPVI and compare it to patients who underwent endocardial cryoballoon PVI. Methods. 25 patients underwent sPVI and were pair-matched according to age, sex, and AF type with 21 patients who underwent cryoballoon PVI. RV function was measured using tricuspid annular plane systolic excursion (TAPSE) and RV strain with 2D speckle tracking. Echocardiography was performed at baseline and at median 6-month follow-up. Results. Age was 54 ± 9 years and 84% were male; AF was paroxysmal in 92%. In the sPVI group, TAPSE was reduced with 31% at follow-up echocardiography (p<0.001) and RV strain showed a 25% reduction compared to baseline (p=0.018). In the control group, TAPSE and RV strain did not change significantly (−3% and +13%, p=0.410 and p=0.148). Change in TAPSE and RV strain was significantly different between groups (p≤0.001 and p=0.005). Conclusions. This study shows that RV function is significantly decreased following sPVI. This effect was not observed in the cryoballoon PVI control group

Amphotericin forms an extramembranous and fungicidal sterol sponge.

For over 50 years, amphotericin has remained the powerful but highly toxic last line of defense in treating life-threatening fungal infections in humans with minimal development of microbial resistance. Understanding how this small molecule kills yeast is thus critical for guiding development of derivatives with an improved therapeutic index and other resistance-refractory antimicrobial agents. In the widely accepted ion channel model for its mechanism of cytocidal action, amphotericin forms aggregates inside lipid bilayers that permeabilize and kill cells. In contrast, we report that amphotericin exists primarily in the form of large, extramembranous aggregates that kill yeast by extracting ergosterol from lipid bilayers. These findings reveal that extraction of a polyfunctional lipid underlies the resistance-refractory antimicrobial action of amphotericin and suggests a roadmap for separating its cytocidal and membrane-permeabilizing activities. This new mechanistic understanding is also guiding development of what are to our knowledge the first derivatives of amphotericin that kill yeast but not human cells

Stroke risk in patients with device-detected atrial high-rate episodes

Cardiovascular implantable electronic devices (CIEDs) can detect atrial arrhythmias, i.e. atrial high-rate episodes (AHRE). The thrombo-embolic risk in patients showing AHRE appears to be lower than in patients with clinical atrial fibrillation (AF) and it is unclear whether the former will benefit from oral anticoagulants. Based on currently available evidence, it seems reasonable to consider antithrombotic therapy in patients without documented AF showing AHRE >24 hours and a CHA(2)DS(2)-VASc score (congestive heart failure, hypertension, age >= 75 years [doubled], diabetes mellitus, prior stroke [doubled], vascular disease, age 65-74 years and female sex) >= 1, awaiting definite answers from ongoing randomised clinical trials. In patients with AHR

Resonance Lifetimes from Complex Densities

The ab-initio calculation of resonance lifetimes of metastable anions challenges modern quantum-chemical methods. The exact lifetime of the lowest-energy resonance is encoded into a complex "density" that can be obtained via complex-coordinate scaling. We illustrate this with one-electron examples and show how the lifetime can be extracted from the complex density in much the same way as the ground-state energy of bound systems is extracted from its ground-state density

Are entrepreneurs' forecasts of economic indicators biased?

Insight into the investment behaviour of firms is central in understanding economic dynamics. A critical question, however, is whether firms provide sufficiently reliable data to enable them to make plausible forecasts at the meso (regional or sectoral) level. This paper analyses Dutch investment forecasts at different levels of aggregation. The central research question is whether entrepreneurs, individually or as a group, make systematic errors in their investment forecasts. A statistical test reveals that investment forecasts are not biased at the aggregated (regional and sectoral) level. At the micro level, however, there is a significant bias. Hence, using aggregated (regional and sectoral) data to test the lack of bias (unbiasedness) of forecasts may lead to the wrong conclusions. Moreover, aggregated investment forecasts may then be an inappropriate source for policy recommendations, despite their seemingly high reliability. This finding may in principle be valid for many European countries, since data collection on investment is organized in similar ways throughout Europe

From the Expected to the Desired Future of Passenger Transport

Sustainability as an unambiguous policy goal is not a priori secured, as is clearly shown in the transport sector, where the negative externalities are still increasing despite official policies aiming at a reduction of these external costs and at the achievement of a sustainable transport system. To analyse why this is the case, a conceptual model is developed in this paper, in which stakeholders are identified which influence sustainable transport policies. These stakeholders are individuals, the public sector (subdivided into politicians and civil servants), international organizations and pressure groups (car industry, oil industry, car users and environmental groups). It appears that - although it may be assumed that nobody desires an unsustainable future - most incentives and mechanisms in our conceptual model of the decision-making process hamper the achievement of a sustainable transport system. In the second part - by way of empirical test - results of a questionnaire among Dutch transportation experts on the expected and desired future of European passenger transport are concisely discussed, in which the year 2030 is taken as a reference year. It appears that in the expected future the stakeholders largely behave as predicted in the conceptual model. I

Neuropathic-like symptoms and the association with joint-specific function and quality of life in patients with hip and knee osteoarthritis

Objective There is an association between osteoarthritis-related pain severity and function, yet clear evidence about the sole influence of neuropathic-like symptoms on joint function and health-related quality of life (HRQoL) is lacking. Previous studies among knee OA patients show an association between neuropathic-like symptoms, lower functional status and lower quality of life, however analyses were unadjusted or had limited adjustment for influential covariates like pain intensity. The aim of this study was therefore to determine the influence of neuropathic-like symptoms-adjusted for multiple influential covariates-on joint-specific function and HRQoL in hip and knee OA patients. Methods In this observational study 255 patients (117 with hip OA and 138 with knee OA) completed the modified painDETECT questionnaire (mPDQ) to identify subjects with neuropathic-like symptoms (mPDQ score>12, possible neuropathic pain [NP] phenotype). The WOMAC and the RAND-36 were used to asses respectively function and HRQoL. Results were adjusted stepwise for age, sex and BMI (Model 1); back disorder, painful body regions, comorbidities and previous surgery (Model 2); and pain intensity and analgesic usage (Model 3). Results A possible NP phenotype was experienced by 37% of hip and 46% of knee OA patients. Final model 3 analysis revealed that hip OA patients with neuropathic-like symptoms scored significantly lower on pain-related aspects of HRQoL (GRAND-36 bodily pain: 6.8 points, p = 0.047) compared to patients with the unlikely NP phenotype. In knee OA patients, a possible NP phenotype was associated with diminished joint function (AWOMAC domains ranging 7.1 to 10.5 points, p Conclusion Neuropathic-like symptoms deteriorate the subjective rating of pain-related quality of life in hip OA patients and significantly influence function in knee OA patients

Site-specific perturbations of alpha-synuclein fibril structure by the Parkinson's disease associated mutations A53T and E46K.

PMCID: PMC3591419This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Parkinson's disease (PD) is pathologically characterized by the presence of Lewy bodies (LBs) in dopaminergic neurons of the substantia nigra. These intracellular inclusions are largely composed of misfolded α-synuclein (AS), a neuronal protein that is abundant in the vertebrate brain. Point mutations in AS are associated with rare, early-onset forms of PD, although aggregation of the wild-type (WT) protein is observed in the more common sporadic forms of the disease. Here, we employed multidimensional solid-state NMR experiments to assess A53T and E46K mutant fibrils, in comparison to our recent description of WT AS fibrils. We made de novo chemical shift assignments for the mutants, and used these chemical shifts to empirically determine secondary structures. We observe significant perturbations in secondary structure throughout the fibril core for the E46K fibril, while the A53T fibril exhibits more localized perturbations near the mutation site. Overall, these results demonstrate that the secondary structure of A53T has some small differences from the WT and the secondary structure of E46K has significant differences, which may alter the overall structural arrangement of the fibrils

Right Heart Dysfunction in Heart Failure with Preserved Ejection Fraction:the Impact of Atrial Fibrillation

BACKGROUND: Right ventricular (RV) dysfunction and atrial fibrillation (AF) frequently coexist in heart failure with preserved ejection fraction (HFpEF). The mechanisms underlying the association between AF and RV dysfunction are incompletely understood. METHODS AND RESULTS: 102 patients were identified. RV function was assessed using multiple echocardiographic parameters and dysfunction was present if ≥2 parameters were below the recommended cutoff. RV function, right atrial (RA) reservoir strain and RA emptying fraction, were compared between AF and sinus rhythm. 91 patients with sufficient echocardiographic quality were included: 45 (50%) had no history of AF; 14 (15%) had prior AF while in sinus rhythm; 32 (35%) had current AF. The prevalence of RV dysfunction varied across subgroups never AF, prior AF and current AF (20%, 43% and 63%, respectively, p=0.001). AF was associated with RV dysfunction (OR 4.70 [1.82-12.1], p=0.001) - independent of pulmonary pressures. In patients in sinus rhythm with prior AF, RA emptying fraction was lower compared to patients without AF history (41 vs. 60%, p=0.002). Prior AF was also associated with reduced RA reservoir strain (OR 4.57 [1.05-19.9], p=0.04) - independent of RV end-diastolic pressure. CONCLUSIONS: Atrial fibrillation is strongly related to reduced RV and RA function in HFpEF, independent of pulmonary pressures

Pupillary Responses to High-Irradiance Blue Light Correlate with Glaucoma Severity

PurposeTo evaluate whether a chromatic pupillometry test can be used to detect impaired function of intrinsically photosensitive retinal ganglion cells (ipRGCs) in patients with primary open-angle glaucoma (POAG) and to determine if pupillary responses correlate with optic nerve damage and visual loss.DesignCross-sectional study.ParticipantsOne hundred sixty-one healthy controls recruited from a community polyclinic (55 men; 151 ethnic Chinese) and 40 POAG patients recruited from a glaucoma clinic (22 men; 35 ethnic Chinese) 50 years of age or older.MethodsSubjects underwent monocular exposure to narrowband blue light (469 nm) or red light (631 nm) using a modified Ganzfeld dome. Each light stimulus was increased gradually over 2 minutes to activate sequentially the rods, cones, and ipRGCs that mediate the pupillary light reflex. Pupil diameter was recorded using an infrared pupillography system.Main Outcome MeasuresPupillary responses to blue light and red light were compared between control subjects and those with POAG by constructing dose-response curves across a wide range of corneal irradiances (7–14 log photons/cm2 per second). In patients with POAG, pupillary responses were evaluated relative to standard automated perimetry testing (Humphrey Visual Field [HVF]; Carl Zeiss Meditec, Dublin, CA) and scanning laser ophthalmoscopy parameters (Heidelberg Retinal Tomography [HRT]; Heidelberg Engineering, Heidelberg, Germany).ResultsThe pupillary light reflex was reduced in patients with POAG only at higher irradiance levels, corresponding to the range of activation of ipRGCs. Pupillary responses to high-irradiance blue light associated more strongly with disease severity compared with responses to red light, with a significant linear correlation observed between pupil diameter and HVF mean deviation (r = −0.44; P = 0.005) as well as HRT linear cup-to-disc ratio (r = 0.61; P < 0.001) and several other optic nerve head parameters.ConclusionsIn glaucomatous eyes, reduced pupillary responses to high-irradiance blue light were associated with greater visual field loss and optic disc cupping. In POAG, a short chromatic pupillometry test that evaluates the function of ipRGCs can be used to estimate the degree of damage to retinal ganglion cells that mediate image-forming vision. This approach could prove useful in detecting glaucoma