SLO-2 Is Cytoprotective and Contributes to Mitochondrial Potassium Transport

Mitochondrial potassium channels are important mediators of cell protection against stress. The mitochondrial large-conductance “big” K+ channel (mBK) mediates the evolutionarily-conserved process of anesthetic preconditioning (APC), wherein exposure to volatile anesthetics initiates protection against ischemic injury. Despite the role of the mBK in cardioprotection, the molecular identity of the channel remains unknown. We investigated the attributes of the mBK using C. elegans and mouse genetic models coupled with measurements of mitochondrial K+ transport and APC. The canonical Ca2+-activated BK (or “maxi-K”) channel SLO1 was dispensable for both mitochondrial K+ transport and APC in both organisms. Instead, we found that the related but physiologically-distinct K+ channel SLO2 was required, and that SLO2-dependent mitochondrial K+ transport was triggered directly by volatile anesthetics. In addition, a SLO2 channel activator mimicked the protective effects of volatile anesthetics. These findings suggest that SLO2 contributes to protection from hypoxic injury by increasing the permeability of the mitochondrial inner membrane to K+

In vitro and in vivo aspects of cascade impactor tests and inhaler performance: A review

The purpose of this review is to discuss the roles of cascade impactor (CI) data in inhaler assessment and to examine the relationship between aerodynamic particle size distribution (APSD) and the clinical response to inhaled drugs. A systematic literature search of studies linking APSD to clinical response was undertaken. Two distinct roles for CI-generated data were identified: (1) the control of inhaler/drug product quality; and (2) the provision of data that may be predictive of particle deposition in the respiratory tract. Method robustness is required for the former application, combined with simplicity in operation, resulting in rudimentary attempts to mimic the anatomy of the respiratory tract. The latter necessitates making the apparatus and its operation more closely resemble patient use of the inhaler. A CI cannot perfectly simulate the respiratory tract, since it operates at constant flow rate, while the respiratory cycle has a varying flow-time profile. On the basis of a review of studies linking APSD to clinical response of inhaled drugs, it is concluded that attempts to use CI-generated data from quality control testing to compare products for bioequivalence are likely to have only limited success, as links between laboratory-measured APSD, particle deposition in the respiratory tract, and clinical response are not straightforward

Addressing health literacy in patient decision aids

MethodsWe reviewed literature for evidence relevant to these two aims. When high-quality systematic reviews existed, we summarized their evidence. When reviews were unavailable, we conducted our own systematic reviews.ResultsAim 1: In an existing systematic review of PtDA trials, lower health literacy was associated with lower patient health knowledge (14 of 16 eligible studies). Fourteen studies reported practical design strategies to improve knowledge for lower health literacy patients. In our own systematic review, no studies reported on values clarity per se, but in 2 lower health literacy was related to higher decisional uncertainty and regret. Lower health literacy was associated with less desire for involvement in 3 studies, less question-asking in 2, and less patient-centered communication in 4 studies; its effects on other measures of patient involvement were mixed. Only one study assessed the effects of a health literacy intervention on outcomes; it showed that using video to improve the salience of health states reduced decisional uncertainty. Aim 2: In our review of 97 trials, only 3 PtDAs overtly addressed the needs of lower health literacy users. In 90% of trials, user health literacy and readability of the PtDA were not reported. However, increases in knowledge and informed choice were reported in those studies in which health literacy needs were addressed.ConclusionLower health literacy affects key decision-making outcomes, but few existing PtDAs have addressed the needs of lower health literacy users. The specific effects of PtDAs designed to mitigate the influence of low health literacy are unknown. More attention to the needs of patients with lower health literacy is indicated, to ensure that PtDAs are appropriate for lower as well as higher health literacy patients

De novo gain-of-function KCNT1 channel mutations cause malignant migrating partial seizures of infancy

International audienc