Previous research has described the effects of eight

Previous research has described the effects of eight-week mindfulness meditation instruction on neural connectivity (e.g., ), and Shao further extends this work. The Shao study is a note-worthy contribution, especially related to the rigorous randomized active-control study design, longitudinal approach, and correlation of affective and neural connectivity changes. Shao et al. have chosen a relaxation program control condition in order to discern the effects of meditation instruction beyond non-specific benefits of a positive peer-group activity. The longitudinal nature of the trial further strengthens the findings, as differences in changes between study arms seen post-group are attributable to the meditation aspect of the intervention. Given these methodological strengths, the authors show salient effects of the eight-week meditation program related to resting state neural connectivity (increased connectivity from the pons to posterior cingulate substance p (PCC)/precuneus) and affective processing (“neutralizing” affective processing of positive and negative stimuli). Further, the resting state changes in neural connectivity from pons to PCC/precuneus predicted the changes in affective processing, suggesting that the eight-week meditation program leads to changes in the regulatory neural network both during affective evaluation and at rest. These are notable findings further illustrating the complex interplay between neural connectivity and affective processing. Additional research is needed to examine the clinical implications of this work among elderly patients and to explore the generalizability of the findings to other populations. Disclosure
Recently, published a study proposing that clevidipine\'s complex mechanism of action might be responsible for relieving dyspnea in acute heart failure (AHF) patients . Clevidipine was approved by Food and Drug Administration (FDA) (2008) as a third generation dihydropyridine (DHP) calcium channel blocker for the management of perioperative acute hypertension (; ). In 2014, Peacock et al. published the results of a randomized, open-label active control study (PRONTO) evaluating the efficacy of clevidipine versus standard of care (SOC) anti-hypertensive therapy and concluded that clevidipine was responsible for a rapid reduction in blood pressure and dyspnea improvement in hypertensive AHF patients (). Calcium influx during depolarization in vascular smooth muscle (VSM) is prevented by clevidipine administration, blocking intracellular phosphodiesterase with an increase in guanosine monophosphate. This mechanism is responsible for an inhibition in VSM contractility associated with cardiopulmonary and systemic vasodilation (). A reverse translational medicine approach was used by in order to test the idea that, in human lungs, a unique combination of Ca1.2 splice variants is expressed with a higher affinity for clevidipine than the same splice variant in other tissue. The authors refine the general understanding of how pannexin-1 (Panx1), known to act as a major adenosine triphosphate (ATP) release channel, affects Ca1.2 pharmacology and increases its affinity for clevidipine. Further research was encouraged in order to clarify the role of splice variants to the pathophysiology of AHF in the light of a new paradigm generated by Panx1/Ca1.2 interaction (). acknowledged the extended body of research conducted over the last 18years since clevidipine was approved as an investigational new drug, and its importance in gaining a better understanding of its mechanism of action (). Their work focused on testing the hypothesis that specific CACNA1C splice variants are encoding for Ca1.2 in lung tissue with a different pharmacological profile for clevidipine when compared to the same variants expressed in other tissues. They also considered the hypothesis that clevidipine-induced dyspnea relief is due to clevidipine acting on Panx1 channels in lung tissue. The authors considered the possibility that Panx1 associates with Ca1.2 in lung tissue, resulting in an increased affinity of Ca1.2 for clevidipine ().