Coronary Microvascular Dysfunction, Microvascular Angina, and Treatment Strategies

AbstractAngina without coronary artery disease (CAD) has substantial morbidity and is present in 10% to 30% of patients undergoing angiography. Coronary microvascular dysfunction (CMD) is present in 50% to 65% of these patients. The optimal treatment of this cohort is undefined. We performed a systematic review to evaluate treatment strategies for objectively-defined CMD in the absence of CAD. We included studies assessing therapy in human subjects with angina and coronary flow reserve or myocardial perfusion reserve <2.5 by positron emission tomography, cardiac magnetic resonance imaging, dilution methods, or intracoronary Doppler in the absence of coronary artery stenosis ≥50% or structural heart disease. Only 8 papers met the strict inclusion criteria. The papers were heterogeneous, using different treatments, endpoints, and definitions of CMD. The small sample sizes severely limit the power of these studies, with an average of 11 patients per analysis. Studies evaluating sildenafil, quinapril, estrogen, and transcutaneous electrical nerve stimulation application demonstrated benefits in their respective endpoints. No benefit was found with L-arginine, doxazosin, pravastatin, and diltiazem. Our systematic review highlights that there is little data to support therapies for CMD. We assess the data meeting rigorous inclusion criteria and review the related but excluded published data. We additionally describe the next steps needed to address this research gap, including a standardized definition of CMD, routine assessment of CMD in studies of chest pain without obstructive CAD, and specific therapy assessment in the population with confirmed CMD

Optimal trapping wavelengths of Cs2_2 molecules in an optical lattice

The present paper aims at finding optimal parameters for trapping of Cs$_2$ molecules in optical lattices, with the perspective of creating a quantum degenerate gas of ground-state molecules. We have calculated dynamic polarizabilities of Cs$_2$ molecules subject to an oscillating electric field, using accurate potential curves and electronic transition dipole moments. We show that for some particular wavelengths of the optical lattice, called "magic wavelengths", the polarizability of the ground-state molecules is equal to the one of a Feshbach molecule. As the creation of the sample of ground-state molecules relies on an adiabatic population transfer from weakly-bound molecules created on a Feshbach resonance, such a coincidence ensures that both the initial and final states are favorably trapped by the lattice light, allowing optimized transfer in agreement with the experimental observation

A comparative genomics multitool for scientific discovery and conservation

A whole-genome alignment of 240 phylogenetically diverse species of eutherian mammal-including 131 previously uncharacterized species-from the Zoonomia Project provides data that support biological discovery, medical research and conservation. The Zoonomia Project is investigating the genomics of shared and specialized traits in eutherian mammals. Here we provide genome assemblies for 131 species, of which all but 9 are previously uncharacterized, and describe a whole-genome alignment of 240 species of considerable phylogenetic diversity, comprising representatives from more than 80% of mammalian families. We find that regions of reduced genetic diversity are more abundant in species at a high risk of extinction, discern signals of evolutionary selection at high resolution and provide insights from individual reference genomes. By prioritizing phylogenetic diversity and making data available quickly and without restriction, the Zoonomia Project aims to support biological discovery, medical research and the conservation of biodiversity.Peer reviewe

Mapping alterations to the endogenous elemental distribution within the lateral ventricles and choroid plexus in brain disorders using X-ray fluorescence imaging

The choroid plexus and cerebral ventricles are critical structures for the production of cerebral spinal fluid (CSF) and play an important role in regulating ion and metal transport in the brain, however many aspects of its roles in normal physiology and disease states, such as psychiatric illness, remain unknown. The choroid plexus is difficult to examine in vivo, and in situ ex vivo, and as such has typically been examined indirectly with radiolabeled tracers or ex vivo stains, making measurements of the endogenous K+, Cl-, and Ca+ distributions unreliable. In the present study, we directly examined the distribution of endogenous ions and biologically relevant transition metals in the choroid plexus and regions surrounding the ventricles (ventricle wall, cortex, corpus callosum, striatum) using X-ray fluorescence imaging (XFI). We find that the choroid plexus was rich in Cl- and Fe while K+ levels increase further from the ventricle as Cl- levels decrease, consistent with the known role of ion transporters in the choroid plexus CSF production. A polyI:C offspring displayed enlarged ventricles, elevated Cl- surrounding the ventricles, and intraventricular calcifications. These observations fit with clinical findings in patients with schizophrenia and suggest maternal treatment with polyI:C may lead to dysfunctional ion regulation in offspring. This study demonstrates the power of XFI for examining the endogenous elemental distributions of the ventricular system in healthy brain tissue as well as disease models

Lessons from non-canonical splicing

Recent improvements in experimental and computational techniques that are used to study the transcriptome have enabled an unprecedented view of RNA processing, revealing many previously unknown non-canonical splicing events. This includes cryptic events located far from the currently annotated exons and unconventional splicing mechanisms that have important roles in regulating gene expression. These non-canonical splicing events are a major source of newly emerging transcripts during evolution, especially when they involve sequences derived from transposable elements. They are therefore under precise regulation and quality control, which minimizes their potential to disrupt gene expression. We explain how non-canonical splicing can lead to aberrant transcripts that cause many diseases, and also how it can be exploited for new therapeutic strategies

Development and Testing of an Expectations Survey for Patients Undergoing Foot and Ankle Surgery

Category: Other Introduction/Purpose: Functional outcomes scores routinely used in orthopedic research are limited in that they are developed solely from a surgeon’s perspective. Very few studies have investigated patients’ expectations from foot and ankle surgery. Many authors have reported on patient satisfaction, but rarely on expectations, which may vary widely between patients and even strongly affect satisfaction. In this cross-sectional study, we aimed to develop and test a patient-derived expectations survey for patients undergoing foot and ankle surgery. Methods: Using a three-phase process, we developed and tested a patient-derived expectations survey. Patients with a wide spectrum of foot and ankle diagnoses were enrolled, including the major diagnoses of ankle arthritis, ankle instability, ankle osteochondral lesions, flatfoot deformity, hallux valgus, and hallux rigidus. In phase 1, patients were interviewed preoperatively with open-ended questions about their expectations from surgery. Responses were independently assessed by three reviewers using qualitative techniques. Major concepts were grouped into categories which were used to form a draft survey. In phase 2, the survey was administered to preoperative patients on two occasions to establish test-retest reliability. In phase 3, the final survey items were selected based on weighted kappa values for response concordance and clinical relevance, and a scoring rubric was developed. Results: In phase 1, 94 preoperative patients with diverse foot or ankle pathology (mean age 50 ± 15 years, 63% women) volunteered 655 expectations. 29 representative categories were discerned by qualitative analysis and became the draft survey. In phase 2, another 60 patients (mean age 55 ± 15 years, 60% women) completed the draft survey twice preoperatively, separated by an average of 4 days. In phase 3, 23 items were retained for the final survey. For retained items, the average weighted kappa value was 0.54 (Table). An overall score is calculated based on the number of expectations and the amount of improvement expected and ranges from 0-100, with higher scores indicating more expectations. For patients in phase 2, mean scores for both administrations were 65 and 66 and approximated normal distributions. Cronbach alpha coefficients were 0.88 and 0.90, and the intraclass correlation coefficient between scores was 0.78. Conclusion: We developed a patient-derived survey specific to foot and ankle surgery that is valid, reliable, and applicable to diverse diagnoses. It measures physical as well as psychological expectations, encompassing symptoms, function, mobility, work and social activities, exercise/sports, pain medications, shoewear, and appearance. The survey generates an overall score that is easy to calculate and interpret, and thus offers a practical and comprehensive way to record patients’ expectations. In the future, this survey may be used as a means to assess patient satisfaction with surgery as determined by the fulfillment of their expectations