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Ca2+ dynamics and oxidative signaling are fundamental mechanisms for mitochondrial bioenergetics and cell function. The MCU complex is the major pathway by which these signals are integrated in mitochondria. Whether and how these coactive elements interact with MCU have not been established. As an approach toward understanding the regulation of MCU channel by oxidative milieu, we adapted inflammatory and hypoxia models. We identified the conserved cysteine 97 (Cys-97) to be the only reactive thiol in human MCU that undergoes S-glutathionylation. Furthermore, biochemical, structural, and superresolution imaging analysis revealed that MCU oxidation promotes MCU higher order oligomer formation. Both oxidation and mutation of MCU Cys-97 exhibited persistent MCU channel activity with higher [Ca2+]m uptake rate, elevated mROS, and enhanced [Ca2+]m overload-induced cell death. In contrast, these effects were largely independent of MCU interaction with its regulators. These findings reveal a distinct functional role for Cys-97 in ROS sensing and regulation of MCU activity.
Alzheimer's disease (AD) is common among older adults and leads to significant disability. Volatile anesthetic gases administered during general anesthesia (GA) have been hypothesized to be a risk factor for the development of AD. The objective of this study is to systematically review the association between exposure to GA and risk of AD.
Airway guidelines recommend an emergency surgical airway as a potential life-saving treatment in a "Can't Intubate, Can't Oxygenate" (CICO) situation. Surgical airways can be achieved either through a cricothyroidotomy or tracheostomy. The current literature has limited data regarding complications of cricothyroidotomy and tracheostomy in an emergency situation. The objective of this systematic review is to analyze complications following cricothyroidotomy and tracheostomy in airway emergencies.
Airway guidelines recommend the use of ultrasound to localize the cricothyroid membrane prior to airway manipulation in difficult airways. In this study, we aimed to determine the amount of training anesthesia trainees would need to achieve competence in bedside ultrasound to identify the cricothyroid membrane.
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