E1784K is the most common mixed long QT syndrome/Brugada syndrome mutant in the cardiac voltage-gated sodium channel NaV1.5. E1784K shifts the midpoint of the channel conductance-voltage relationship to more depolarized membrane potentials and accelerates the rate of channel fast inactivation. The depolarizing shift in the midpoint of the conductance curve in E1784K is exacerbated by low extracellular pH. We tested whether the E1784K mutant shifts the channel conductance curve to more depolarized membrane potentials by affecting the channel voltage-sensors. We measured ionic currents and gating currents at pH 7.4 and pH 6.0 in Xenopus laevis oocytes. Contrary to our expectation, the movement of gating charges is shifted to more hyperpolarized membrane potentials by E1784K. Voltage-clamp fluorimetry experiments show that this gating charge shift is due to the movement of the DIVS4 voltage-sensor being shifted to more hyperpolarized membrane potentials. Using a model and experiments on fast inactivation-deficient channels, we show that changes to the rate and voltage-dependence of fast inactivation are sufficient to shift the conductance curve in E1784K. Our results localize the effects of E1784K to DIVS4, and provide novel insight into the role of the DIV-VSD in regulating the voltage-dependencies of activation and fast inactivation.
Thoroughly reviewing the literature on developmental progress assessment, St. Onge et al. outline how explicitly mapping student development can help programs, students, and faculty.
Background Approximately one-quarter of emergency department (ED) visits for alcohol withdrawal result in unscheduled 1-week ED return visits, but it is unclear what patient and clinical factors may impact this outcome Methods From January 1, 2015, to December 31, 2018, at three urban EDs in Vancouver, Canada, we studied patients who were discharged with a primary or secondary diagnosis of alcohol withdrawal. We performed a structured chart review to ascertain patient characteristics, ED treatments, and the outcome of an ED return within 1 week of discharge. We used univariable and multivariable Bayesian binomial regression to identify characteristics associated with being in the upper quartile of 1-week ED revisits.
ResultsWe collected 935 ED visits among 593 unique patients. Median age was 45 years (interquartile range 34 to 55 years) and 71% were male. The risk of a 1-week ED revisit was 15.0% (IQR 12.3; 19.5%). After adjustment, factors independently associated with a high risk for return included any prior ED visit within 30 days, no fixed address, initial blood alcohol level > 45 mmol/L, and initial Clinical Institute Withdrawal Assessment-alcohol revised score > 23. These factors explained 41% of the overall variance in revisits. Conclusion Among discharged ED patients with alcohol withdrawal, we describe high-risk patient characteristics associated with 1-week ED revisits, and these findings may assist clinicians to facilitate appropriate discharge planning with access to integrated follow-up support.
Keywords Alcohol use disorder • Alcohol withdrawal
RésuméContexte Environ un quart des visites aux urgences pour sevrage alcoolique se traduit par un retour non programmé aux urgences pendant une semaine, mais les facteurs cliniques et relatifs aux patients qui peuvent avoir une incidence sur ce résultat ne sont pas clairs. Méthodes Du 1er janvier 2015 au 31 décembre 2018, dans trois urgences urbaines de Vancouver, au Canada, nous avons étudié les patients qui sont sortis avec un diagnostic primaire ou secondaire de sevrage alcoolique. Nous avons procédé * Frank X. Scheuermeyer
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