Proceedings of the National Academy of Sciences of the United States of America
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Proc. Natl. Acad. Sci. U.S.A. · Aug 2018
Multicenter StudyPatient-physician gender concordance and increased mortality among female heart attack patients.
Very interesting study covering 20 years of Floridian ED patient admissions for myocardial infarct, looking specifically at the influence of gender-discordance between patient and doctor.
The headline finding was that female heart-attack patients experienced lower survival when treated by a male physician than when by a female physician. Baseline mortality across all patients was 11.9%, with a 1.5% absolute survival decrease when compared to male patients treated by female physicians.
Although on the surface this absolute effect size could be misinterpreted as small, it represents a 12% relative risk difference – quite meaningful when we are considering mortality from the leading cause of death in the U.S.
Could the researchers suggest a reason?
The authors identified two interesting points:
- Female patients treated in EDs with a higher percentage or a higher number of female physicians were more likely to survive. Although true of both care from a female or male physician, the beneficial survival effect of a greater female physician presence, was more marked when treated by a male doctor.
- Female patients treated by male physicians were also more likely to survive when the male physician had previously seen more female patients (0.02% increased survival for each female patient seen in the last quarter!).
summary"These results suggest a reason why gender inequality in heart attack mortality persists: Most physicians are male, and male physicians appear to have trouble treating female patients." – Greenwood, 2018
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Proc. Natl. Acad. Sci. U.S.A. · Aug 2018
Junctional membrane Ca2+ dynamics in human muscle fibers are altered by malignant hyperthermia causative RyR mutation.
We used the nanometer-wide tubules of the transverse tubular (t)-system of human skeletal muscle fibers as sensitive sensors for the quantitative monitoring of the Ca2+-handling properties in the narrow junctional cytoplasmic space sandwiched between the tubular membrane and the sarcoplasmic reticulum cisternae in single muscle fibers. The t-system sealed with a Ca2+-sensitive dye trapped in it is sensitive to changes in ryanodine receptor (RyR) Ca2+ leak, the store operated calcium entry flux, plasma membrane Ca pump, and sodium-calcium exchanger activities, thus making the sealed t-system a nanodomain Ca2+ sensor of Ca2+ dynamics in the junctional space. ⋯ Using this approach we show that the muscle fibers from MH-susceptible individuals display leakier RyRs and a greater capacity to extrude Ca2+ across the t-system membrane compared with fibers from controls. This study provides a quantitative way to assess the effect of RyR variants on junctional membrane Ca2+ handling under defined ionic conditions.
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Proc. Natl. Acad. Sci. U.S.A. · Aug 2018
Mavacamten stabilizes an autoinhibited state of two-headed cardiac myosin.
We used transient biochemical and structural kinetics to elucidate the molecular mechanism of mavacamten, an allosteric cardiac myosin inhibitor and a prospective treatment for hypertrophic cardiomyopathy. We find that mavacamten stabilizes an autoinhibited state of two-headed cardiac myosin not found in the single-headed S1 myosin motor fragment. We determined this by measuring cardiac myosin actin-activated and actin-independent ATPase and single-ATP turnover kinetics. ⋯ Furthermore, actin changes the structure of the autoinhibited state by forcing myosin lever-arm rotation. Mavacamten slows this rotation in two-headed myosin but does not prevent it. We conclude that cardiac myosin is regulated in solution by an interaction between its two heads and propose that mavacamten stabilizes this state.