Role of K(ATP)(+) channels in regulation of systemic, pulmonary, and coronary vasomotor tone in exercising swine

The role of ATP-sensitive K(+) (K(ATP)(+)) channels in vasomotor tone regulation during metabolic stimulation is incompletely understood. Consequently, we studied the contribution of K(ATP)(+) channels to vasomotor tone regulation in the systemic, pulmonary, and coronary vascular bed in nine treadmill-exercising swine. Exercise up to 85% of maximum heart rat

Interferometry with Bose-Einstein Condensates in Microgravity

Atom interferometers covering macroscopic domains of space-time are a spectacular manifestation of the wave nature of matter. Due to their unique coherence properties, Bose-Einstein condensates are ideal sources for an atom interferometer in extended free fall. In this paper we report on the realization of an asymmetric Mach-Zehnder interferometer operated with a Bose-Einstein condensate in microgravity. The resulting interference pattern is similar to the one in the far-field of a double-slit and shows a linear scaling with the time the wave packets expand. We employ delta-kick cooling in order to enhance the signal and extend our atom interferometer. Our experiments demonstrate the high potential of interferometers operated with quantum gases for probing the fundamental concepts of quantum mechanics and general relativity.Comment: 8 pages, 3 figures; 8 pages of supporting materia

Cube law, condition factor and weight-length relationships: history, meta-analysis and recommendations

This study presents a historical review, a meta-analysis, and recommendations for users about weight–length relationships, condition factors and relative weight equations. The historical review traces the developments of the respective concepts. The meta-analysis explores 3929 weight–length relationships of the type W = aLb for 1773 species of fishes. It shows that 82% of the variance in a plot of log a over b can be explained by allometric versus isometric growth patterns and by different body shapes of the respective species. Across species median b = 3.03 is significantly larger than 3.0, thus indicating a tendency towards slightly positive-allometric growth (increase in relative body thickness or plumpness) in most fishes. The expected range of 2.5 < b < 3.5 is confirmed. Mean estimates of b outside this range are often based on only one or two weight–length relationships per species. However, true cases of strong allometric growth do exist and three examples are given. Within species, a plot of log a vs b can be used to detect outliers in weight–length relationships. An equation to calculate mean condition factors from weight–length relationships is given as Kmean = 100aLb−3. Relative weight Wrm = 100W/(amLbm) can be used for comparing the condition of individuals across populations, where am is the geometric mean of a and bm is the mean of b across all available weight–length relationships for a given species. Twelve recommendations for proper use and presentation of weight–length relationships, condition factors and relative weight are given

Length of hospital stay for elective electrophysiological procedures: a survey from the European Heart Rhythm Association

AIMS: Electrophysiological (EP) operations that have traditionally involved long hospital lengths of stay (LOS) are now being undertaken as day case procedures. The coronavirus disease-19 pandemic served as an impetus for many centres to shorten LOS for EP procedures. This survey explores LOS for elective EP procedures in the modern era. METHODS AND RESULTS: An online survey consisting of 27 multiple-choice questions was completed by 245 respondents from 35 countries. With respect to de novo cardiac implantable electronic device (CIED) implantations, day case procedures were reported for 79.5% of implantable loop recorders, 13.3% of pacemakers (PMs), 10.4% of implantable cardioverter defibrillators (ICDs), and 10.2% of cardiac resynchronization therapy (CRT) devices. With respect to CIED generator replacements, day case procedures were reported for 61.7% of PMs, 49.2% of ICDs, and 48.2% of CRT devices. With regard to ablations, day case procedures were reported for 5.7% of atrial fibrillation (AF) ablations, 10.7% of left-sided ablations, and 17.5% of right-sided ablations. A LOS ≥ 2 days for CIED implantation was reported for 47.7% of PM, 54.5% of ICDs, and 56.9% of CRT devices and for 54.5% of AF ablations, 42.2% of right-sided ablations, and 46.1% of left-sided ablations. Reimbursement (43-56%) and bed availability (20-47%) were reported to have no consistent impact on the organization of elective procedures. CONCLUSION: There is a wide variation in the LOS for elective EP procedures. The LOS for some procedures appears disproportionate to their complexity. Neither reimbursement nor bed availability consistently influenced LOS

The BAH domain of Rsc2 is a histone H3 binding domain

Bromo-adjacent homology (BAH) domains are commonly found in chromatin-associated proteins and fall into two classes; Remodels the Structure of Chromatin (RSC)-like or Sir3-like. Although Sir3-like BAH domains bind nucleosomes, the binding partners of RSC-like BAH domains are currently unknown. The Rsc2 subunit of the RSC chromatin remodeling complex contains an RSC-like BAH domain and, like the Sir3-like BAH domains, we find Rsc2 BAH also interacts with nucleosomes. However, unlike Sir3-like BAH domains, we find that Rsc2 BAH can bind to recombinant purified H3 in vitro, suggesting that the mechanism of nucleosome binding is not conserved. To gain insight into the Rsc2 BAH domain, we determined its crystal structure at 2.4 Å resolution. We find that it differs substantially from Sir3-like BAH domains and lacks the motifs in these domains known to be critical for making contacts with histones. We then go on to identify a novel motif in Rsc2 BAH that is critical for efficient H3 binding in vitro and show that mutation of this motif results in defective Rsc2 function in vivo. Moreover, we find this interaction is conserved across Rsc2-related proteins. These data uncover a binding target of the Rsc2 family of BAH domains and identify a novel motif that mediates this interaction

Alterations in vasomotor control of coronary resistance vessels in remodelled myocardium of swine with a recent myocardial infarction

The mechanism underlying the progressive deterioration of left ventricular (LV) dysfunction after myocardial infarction (MI) towards overt heart failure remains incompletely understood, but may involve impairments in coronary blood flow regulation within remodelled myocardium leading to intermittent myocardial ischemia. Blood flow to the remodelled myocardium is hampered as the coronary vasculature does not grow commensurate with the increase in LV mass and because extravascular compression of the coronary vasculature is increased. In addition to these factors, an increase in coronary vasomotor tone, secondary to neurohumoral activation and endothelial dysfunction, could also contribute to the impaired myocardial oxygen supply. Consequently, we explored, in a series of studies, the alterations in regulation of coronary resistance vessel tone in remodelled myocardium of swine with a 2 to 3-week-old MI. These studies indicate that myocardial oxygen balance is perturbed in remodelled myocardium, thereby forcing the myocardium to increase its oxygen extraction. These perturbations do not appear to be the result of blunted β-adrenergic or endothelial NO-mediated coronary vasodilator influences, and are opposed by an increased vasodilator influence through opening of KATP channels. Unexpectedly, we observed that despite increased circulating levels of noradrenaline, angiotensin II and endothelin-1, α-adrenergic tone remained negligible, while the coronary vasoconstrictor influences of endogenous endothelin and angiotensin II were virtually abolished. We conclude that, early after MI, perturbations in myocardial oxygen balance are observed in remodelled myocardium. However, adaptive alterations in coronary resistance vessel control, consisting of increased vasodilator influences in conjunction with blunted vasoconstrictor influences, act to minimize the impairments of myocardial oxygen balance

Lentiviral Hematopoietic Stem Cell Gene Therapy Corrects Murine Pompe Disease

Pompe disease is an autosomal recessive lysosomal storage disorder characterized by progressive muscle weakness. The disease is caused by mutations in the acid α-glucosidase (GAA) gene. Despite the currently available enzyme replacement therapy (ERT), roughly half of the infants with Pompe disease die before the age of 3 years. Limitations of ERT are immune responses to the recombinant enzyme, incomplete correction of the disease phenotype, lifelong administration, and inability of the enzyme to cross the blood-brain barrier. We previously reported normalization of glycogen in heart tissue and partial correction of the skeletal muscle phenotype by ex vivo hematopoietic stem cell gene therapy. In the present study, using a codon-optimized GAA (GAAco), the enzyme levels resulted in close to normalization of glycogen in heart, muscles, and brain, and in complete normalization of motor function. A large proportion of microglia in the brain was shown to be GAA positive. All astrocytes contained the enzyme, which is in line with mannose-6-phosphate receptor expression and the key role in glycogen storage and glucose metabolism. The lentiviral vector insertion site analysis confirmed no preference for integration near proto-oncogenes. This correction of murine Pompe disease warrants further development toward a cure of the human condition.This publication reports that stem cell gene therapy using a codon-optimized gene encoding acid α-glucosidase (GAA) cures the mouse model of Pompe disease, a lysosomal storage disorder

Improving mental well-being in psychocardiology—a feasibility trial for a non-blended web application as a brief metacognitive-based intervention in cardiovascular disease patients

Background: Many patients with cardiovascular disease also show a high comorbidity of mental disorders, especially such as anxiety and depression. This is, in turn, associated with a decrease in the quality of life. Psychocardiological treatment options are currently limited. Hence, there is a need for novel and accessible psychological help. Recently, we demonstrated that a brief face-to-face metacognitive therapy (MCT) based intervention is promising in treating anxiety and depression. Here, we aim to translate the face-to-face approach into digital application and explore the feasibility of this approach. Methods: We translated a validated brief psychocardiological intervention into a novel non-blended web app. The data of 18 patients suffering from various cardiac conditions but without diagnosed mental illness were analyzed after using the web app over a two-week period in a feasibility trial. The aim was whether a non-blended web app based MCT approach is feasible in the group of cardiovascular patients with cardiovascular disease. Results: Overall, patients were able to use the web app and rated it as satisfactory and beneficial. In addition, there was first indication that using the app improved the cardiac patients’ subjectively perceived health and reduced their anxiety. Therefore, the approach seems feasible for a future randomized controlled trial. Conclusion: Applying a metacognitive-based brief intervention via a non-blended web app seems to show good acceptance and feasibility in a small target group of patients with CVD. Future studies should further develop, improve and validate digital psychotherapy approaches, especially in patient groups with a lack of access to standard psychotherapeutic care

Classification of forest management approaches: a new conceptual framework and its applicability to European forestry

The choice between different forest management practices is a crucial step in short, medium, and long-term decision making in forestry and when setting up measures to support a regional or national forest policy. Some conditions such as biogeographically determined site factors, exposure to major disturbances, and societal demands are predetermined, whereas operational processes such as species selection, site preparation, planting, tending, or thinning can be altered by management. In principle, the concept of a forest management approach provides a framework for decision making, including a range of silvicultural operations that influence the development of a stand or group of trees over time. These operations vary among silvicultural systems and can be formulated as a set of basic principles. Consequently, forest management approaches are essentially defined by coherent sets of forest operation processes at a stand level. Five ideal forest management approaches (FMAs) representing a gradient of management intensity are described using specific sets of basic principles that enable comparison across European forests. Each approach is illustrated by a regional European case study. The observed regional variations resulting from changing species composition, stand density, age structure, stand edges, and site conditions can be interpreted using the FMA framework. Despite being arranged along an intensity gradient, the forest management approaches are not considered to be mutually exclusive, as the range of options allows for greater freedom in selecting potential silvicultural operations. As derived goods and services are clearly affected, the five forest management approaches have implications for sustainability. Thus, management objectives can influence the balance between the economic, ecological, and social dimensions of sustainability. The utility of this framework is further demonstrated through the different contributions to this special issue

Recovery of left ventricular function after primary angioplasty for acute myocardial infarction.

AIMS: To study recovery of segmental wall thickening (SWT), ejection fraction (EF), and end-systolic volume (ESV) after acute myocardial infarction (AMI) in patients who underwent primary stenting with drug-eluting stents. Additionally, to evaluate the predictive value of magnetic resonance imaging (MRI)-based myocardial perfusion and delayed enhancement (DE) imaging. METHODS AND RESULTS: Twenty-two patients underwent cine-MRI, first-pass perfusion, and DE imaging 5 days after successful placement of a drug-eluting stent in the infarct-related coronary artery. Regional myocardial perfusion and the transmural extent of DE were evaluated. A per patient perfusion score was calculated and consisted of a summation of all segmental scores. Myocardial infarct size was quantified by measuring the volume of DE. At 5 months after AMI, cine-MRI was performed and SWT, EF, and ESV were quantified. EF increased from 48+/-11 to 55+/-9% (P<0.01). SWT at 5 months was inversely related to baseline segmental DE scores (P<0.001) and segmental perfusion scores (P<0.001). EF and ESV at 5 months were related to acute infarct size (R(2)=0.65; P<0.001 and R(2)=0.78; P<0.001, respectively) and the calculated perfusion score (R(2)=0.23; P=0.02 and R(2)=0.14; P=0.09, respectively) at baseline. CONCLUSION: Marked recovery of left ventricular function was observed in patients receiving a drug-eluting stent for AMI. DE imaging appears to be a better prognosticator than perfusion imaging