Ionic Components of Electric Current at Rat Corneal Wounds

Peer reviewedPublisher PD

Rhythm monitoring, success definition, recurrence, and anticoagulation after atrial fibrillation ablation: results from an EHRA survey

Atrial fibrillation (AF) is a major challenge for the healthcare field. Pulmonary vein isolation is the most effective treatment for the maintenance of sinus rhythm. However, clinical endpoints for the procedure vary significantly among studies. There is no consensus on the definition of recurrence and no clear roadmap on how to deal with recurrences after a failed ablation. The purpose of this study was to perform a survey in order to show how clinicians currently approach this knowledge gap. An online survey, supported by the European Heart Rhythm Association (EHRA) Scientific Initiatives Committee, was conducted between 1 April 2022 and 8 May 2022. An anonymous questionnaire was disseminated via social media and EHRA newsletters, for clinicians to complete. This consisted of 18 multiple-choice questions regarding rhythm monitoring, definitions of a successful ablation, clinical practices after a failed AF ablation, and the continuance of anticoagulation. A total of 107 replies were collected across Europe. Most respondents (82%) perform routine monitoring for AF recurrences after ablation, with 51% of them preferring a long-term monitoring strategy. Cost was reported to have an impact on the choice of monitoring strategy. Self-screening was recommended by most (71%) of the respondents. The combination of absence of symptoms and recorded AF was the definition of success for most (83%) of the respondents. Cessation of anticoagulation after ablation was an option mostly for patients with paroxysmal AF and a low CHA2DS2-VASc score. The majority of physicians perform routine monitoring after AF ablation. For most physicians, the combination of the absence of symptoms and electrocardiographic endpoints defines a successful result after AF ablation

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Calcium flux at corneal wounds.

<p><b>A. Ca²⁺ concentration.</b> Calcium concentration at unwounded cornea was slightly above background (0.015 mM). After wounding, Ca²⁺ concentraion increased until 20 min then plateaued. <b>B. Ca²⁺ flux.</b> Unwounded cornea showed a small Ca²⁺ efflux. After wounding, calcium efflux at the wound edge increased to reach a maximum value after 20 minutes. This efflux was maintained for up to 90 minutes. Aminophylline had no effect on Ca²⁺ flux. <b>C. Fixation.</b> Calcium concentration was measured for 30 minutes to confirm normal efflux. The eye was then fixed. Subsequent measurements showed a drop in calcium concentration to almost zero, even lower than unwounded values.</p

Sodium flux at corneal wounds.

<p><b>A. Na⁺ concentration.</b> Unwounded cornea had a slighly higher Na⁺ concentration than background. However, upon wounding, the Na⁺ concentration at the wound edge was lower than background (negative values). <b>B. Na⁺ flux.</b> Intact cornea showed a small Na⁺ efflux. On wounding this became a sodium influx which was maintained for 90 min. Both aminophylline and ascorbic acid induced a large Na⁺ efflux at later timepoints (5 min and later; *P<0.01).</p

Distribution and expression of calcium-activated chloride channel-2 (CLC2).

<p><b>A.</b> In unwounded cornea, CLC2 channels were concentrated in the superficial epithelial cells (arrow). <b>B.</b> One hour after wounding, fluorescence was present throughout the entire thickness of the epithelium, showing re-distribution and increased concentration of CLC2 channels. Scale bars 50 µm. <b>C.</b> In human corneal epithelial cell monolayer, scratch wounding induced increased expression of CLC2 channel mRNA (*P<0.05).</p

Potassium flux at corneal wounds.

<p><b>A. K⁺ concentration.</b> Immediately after wounding there was a rapid transient increase of K⁺ concentration. This initial high concentration decreased over 5–20 min after wounding, reaching a stable lower value. <b>B. K⁺ flux.</b> There was a large K⁺ efflux immediately after wounding, which dropped after 20 min. Aminophylline had no effect on the initial peak of efflux, but appeared to enhance efflux at later time points (60–90 min; *P<0.03). <b>C. K⁺ concentration in high [K⁺]</b>. In hi-K⁺ solution (20 mM) the initial peak of K⁺ concentration was absent and the wound showed a lower K⁺ concentration (negative values), indicating K⁺ influx.</p

Chloride flux at corneal wounds A.

<p><b>Cl⁻ concentration.</b> Unwounded cornea had a slighly higher Cl⁻ concentration than background. Upon wounding, the Cl⁻ concentration at the wound edge transiently increased, (5 min) and then decreased, becoming lower than background (negative values) from 10 min onwards. <b>B. Cl⁻ flux.</b> Unwounded cornea had a small chloride efflux. Wounding induced a large, sustained influx which increased with time. Ascorbic acid reversed the chloride influx, giving a small efflux (**P<0.01), but aminophylline significantly enhanced chloride influx at time-points 5–60 min (*P<0.04). <b>C. Wound electric current</b> was significantly reduced in the presence of 200 µM broad-spectrum chloride channel blocker DIDS (#P<0.03).</p