Stratum Corneum Lipid Liposomes: Calcium-Induced Transformation Into Lamellar Sheets

The epidermal water barrier in mammalian stratum corneum is formed of broad lamellar sheets of lipids consisting principally of ceramides (40%), cholesterol (25%), cholesterol sulfate (10%), and free fatty acids (25%). Such lipid mixtures have been shown to form lipid bilayers in the form of small, unilamellar liposomes when sonicated at 80°C in water containing Tris buffer and 100mM NaCl. In the present study it is shown that such liposomes are slowly transformed into large unilamellar liposomes and then into broad lamellar sheets after the addition of stoichiometric amounts of calcium chloride. The presence of free fatty acids was a necessary condition for this calcium-induced fusion. These observations may provide a useful analogy for the transformation of flattened liposomes into broad lamellar sheets that occurs during transition of epidermal granular cells into corneocytes

Descriptors for Pentane-2,4-dione and Its Derivatives

We have used equations for partition coefficients of compounds from water and the gas phase to various solvents to obtain descriptors for pentane-2,4-dione and 21 of its derivatives. These descriptors can then be used to estimate further partition coefficients into a wide variety of solvents. The descriptors also yield information about the properties of pentane-2,4-dione and its derivatives. Pentane-2,4-dione and its alkyl derivatives are quite polar, with substantial hydrogen bond basicity but with no hydrogen bond acidity. In contrast 1,1,1-trifluoropentane-2,4-dione and hexafluoropentan-2,4-dione have significant hydrogen bond acidities

Predictors of short-term clinical response to cardiac resynchronization therapy

Aims: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with symptomatic heart failure and QRS prolongation but there is uncertainty about which patient characteristics predict short-term clinical response. Methods and results: In an individual patient meta-analysis of three double-blind, randomized trials, clinical composite score (CCS) at 6 months was compared in patients assigned to CRT programmed on or off. Treatment–covariate interactions were assessed to measure likelihood of improved CCS at 6 months. MIRACLE, MIRACLE ICD, and REVERSE trials contributed data for this analysis (n = 1591). Multivariable modelling identified QRS duration and left ventricular ejection fraction (LVEF) as predictors of CRT clinical response (P < 0.05). The odds ratio for a better CCS at 6 months increased by 3.7% for every 1% decrease in LVEF for patients assigned to CRT-on compared to CRT-off, and was greatest when QRS duration was between 160 and 180 ms. Conclusions: In symptomatic chronic heart failure patients (NYHA class II–IV), longer QRS duration and lower LVEF independently predict early clinical response to CRT

Developing a collaborative, humanistic interprofessional healthcare culture: a multi-site study

Introduction:Developing a collaborative, humanistic interprofessional healthcare culture requires optimal relational skills, respect, interpersonal cohesion, and role clarity. We developed a longitudinal curriculum to engender these skills and values in institutional leaders. We report results of a qualitative study at seven US-based academic health centers to identify participants’ learning. Methods:At each institution, participants from at least three different professions met in small group sessions twice-monthly over nine months. Sessions focused on relational capacities to enhance leadership and professionalism, and utilized critical reflection and experiential learning to promote teamwork, self-knowledge, communication skills, and address challenges encountered by a healthcare team. Participants completed reflective responses to open-ended questions asking what knowledge, insights, or skills they gained by working in this interprofessional group and applications of their learning. Five investigators analyzed the anonymized responses using the constant comparative method. Results:Overarching themes centered on relationships and the strength of the relational nature of the learning. We observed learning on three levels: a) Intrapersonal learning included self-awareness, mindfulness, and empathy for self that translated to reflections on application of these to teamwork and teaching; b) Interpersonal learning concerned relational skills and teaching about listening, understanding others’ perspectives, appreciation/respect for colleagues, and empathy for others; c) Systems level learning included teaching skills about resilience, conflict management, team dynamics and cultural norms, and appreciation of resources from interprofessional colleagues. Discussion:A curriculum focusing on humanistic teaching for leaders led to new insights and positive changes in relational perspectives. Learning occurred on multiple levels. Many learners reported revising previous assumptions, a marker for transformative learning. Humanistic faculty development can facilitate deep bonds between professions. &nbsp

Neighborhood Racial Discrimination and the Development of Major Depression

This study examined the impact of neighborhood racial discrimination on the development of major depressive disorder (MDD) in a sample of African American women. Participants were 499 women from Georgia and Iowa with no history of MDD who were followed for 9 to 11 years. Several neighborhood characteristics (community social disorder, community cohesion, and community racism) and individual characteristics (negative life events, financial strain, personal outlook, religious involvement, relationship quality, negative affectivity, and individual experiences of racism) were employed as predictors of whether or not the women met criteria for MDD during this period of time. In a multilevel logistic regression analysis, neighborhood-level discrimination as well as individual-level variables including the number of negative life events, financial strain, and negative affectivity were found to be significant predictors of developing MDD. Analyses of cross-level interactions indicated that the effects of neighborhood-level discrimination were moderated by the quality of individuals’ relationships, such that better relationships with others served to lessen the effect of neighborhood discrimination on depression. Implications of these findings for understanding the negative effects of racial discrimination are discussed

Visual Vibrometry: Estimating Material Properties from Small Motions in Video

The estimation of material properties is important for scene understanding, with many applications in vision, robotics, and structural engineering. This paper connects fundamentals of vibration mechanics with computer vision techniques in order to infer material properties from small, often imperceptible motion in video. Objects tend to vibrate in a set of preferred modes. The shapes and frequencies of these modes depend on the structure and material properties of an object. Focusing on the case where geometry is known or fixed, we show how information about an object’s modes of vibration can be extracted from video and used to make inferences about that object’s material properties. We demonstrate our approach by estimating material properties for a variety of rods and fabrics by passively observing their motion in high-speed and regular framerate video.National Science Foundation (U.S.) (Robust Intelligence 1212849 Reconstructive Recognition)Shell Oil CompanyQatar Computing Research InstituteNational Science Foundation (U.S.). Graduate Research Fellowshi

Type of atrial fibrillation and clinical outcomes in patients with heart failure and reduced ejection fraction

Background: Atrial fibrillation (AF) is common in heart failure (HF), but the outcome by type of AF is largely unknown. Objectives: This study investigated outcomes related to type of AF (paroxysmal, persistent or permanent, or new onset) in 2 recent large trials in patients with HF with reduced ejection fraction. Methods: The study analyzed patients in the PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure) and ATMOSPHERE (Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure) trials. Multivariable Cox regression models were used to estimate hazard ratios (HRs) for outcomes related to AF type. Results: Of 15,415 patients, 5,481 (35.6%) had a history of AF at randomization, and of these, 1,645 (30.0%) had paroxysmal AF. Compared with patients without AF, patients with paroxysmal AF at randomization had a higher risk of the primary composite endpoint of cardiovascular death or HF hospitalization (HR: 1.20; 95% confidence interval [CI]: 1.09 to 1.32; p < 0.001), HF hospitalization (HR: 1.34; 95% CI: 1.19 to 1.51; < 0.001), and stroke (HR: 1.34; 95% CI: 1.02 to 1.76; p = 0.037), whereas the corresponding risks in patients with persistent or permanent AF were not elevated. Neither type of AF was associated with higher mortality. New onset AF was associated with the greatest risk of adverse outcomes: primary endpoint (HR: 2.21; 95% CI: 1.80 to 2.71), HF hospitalization (HR: 2.11; 95% CI: 1.58 to 2.81), stroke (HR: 2.20; 95% CI: 1.25 to 3.88), and all-cause mortality (HR: 2.26; 95% CI: 1.86 to 2.74), all p values < 0.001, compared with patients without AF. Anticoagulants were used less often in patients with paroxysmal (53%) and new onset (16%) AF than in patients with persistent or permanent AF (71%). Conclusions: Among HF patients with a history of AF, those with paroxysmal AF were at greater risk of HF hospitalization and stroke than were patients with persistent or permanent AF, underlining the importance of anticoagulant therapy. New onset AF was associated with increased risk of all outcomes. (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255) (Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure [ATMOSPHERE]; NCT00853658

Proline-Dependent Regulation of Clostridium difficile Stickland Metabolism

Clostridium difficile, a proteolytic Gram-positive anaerobe, has emerged as a significant nosocomial pathogen. Stickland fermentation reactions are thought to be important for growth of C. difficile and appear to influence toxin production. In Stickland reactions, pairs of amino acids donate and accept electrons, generating ATP and reducing power in the process. Reduction of the electron acceptors proline and glycine requires the D-proline reductase (PR) and the glycine reductase (GR) enzyme complexes, respectively. Addition of proline in the medium increases the level of PR protein but decreases the level of GR. We report the identification of PrdR, a protein that activates transcription of the PR-encoding genes in the presence of proline and negatively regulates the GR-encoding genes. The results suggest that PrdR is a central metabolism regulator that controls preferential utilization of proline and glycine to produce energy via the Stickland reactions

Prognostic implications of left ventricular global longitudinal strain in heart failure patients with narrow QRS complex treated with cardiac resynchronization therapy: a subanalysis of the randomized EchoCRT trial

Aim: Left ventricular (LV) global longitudinal strain (GLS) reflects LV systolic function and correlates inversely with the extent of LV myocardial scar and fibrosis. The present subanalysis of the Echocardiography Guided CRT trial investigated the prognostic value of LV GLS in patients with narrow QRS complex. Methods and results: Left ventricular (LV) global longitudinal strain (GLS) was measured on the apical 2-, 4- and 3-chamber views using speckle tracking analysis. Measurement of baseline LV GLS was feasible in 755 patients (374 with cardiac resynchronization therapy (CRT)-ON and 381 with CRT-OFF). The median value of LV GLS in the overall population was 7.9%, interquartile range 6.2–10.1%. After a mean follow-up period of 19.4 months, 95 patients in the CRT-OFF group and 111 in the CRT-ON group reached the combined primary endpoint of all-cause mortality and heart failure hospitalization. Each 1% absolute unit decrease in LV GLS was independently associated with 11% increase in the risk to reach the primary endpoint (Hazard ratio 1.11; 95% confidence interval 95% 1.04–1.17, P < 0.001), after adjusting for ischaemic cardiomyopathy and randomization treatment among other clinically relevant variables. When categorizing patients according to quartiles of LV GLS, the primary endpoint occurred more frequently in patients in the lowest quartile (<6.2%) treated with CRT-ON vs. CRT-OFF (45.6% vs. 28.7%, P = 0.009) whereas, no differences were observed in patients with LV GLS ≥6.2% treated with CRT-OFF vs. CRT-ON (23.7% vs. 24.5%, respectively; P  = 0.62). Conclusion: Low LV GLS is associated with poor outcome in heart failure patients with QRS width <130 ms, independent of randomization to CRT or not. Importantly, in the group of patients with the lowest LV GLS quartile, CRT may have a detrimental effect on clinical outcomes