Amygdala 14-3-3ζ as a Novel Modulator of Escalating Alcohol Intake in Mice

Alcoholism is a devastating brain disorder that affects millions of people worldwide. The development of alcoholism is caused by alcohol-induced maladaptive changes in neural circuits involved in emotions, motivation, and decision-making. Because of its involvement in these processes, the amygdala is thought to be a key neural structure involved in alcohol addiction. However, the molecular mechanisms that govern the development of alcoholism are incompletely understood. We have previously shown that in a limited access choice paradigm, C57BL/6J mice progressively escalate their alcohol intake and display important behavioral characteristic of alcohol addiction, in that they become insensitive to quinine-induced adulteration of alcohol. This study used the limited access choice paradigm to study gene expression changes in the amygdala during the escalation to high alcohol consumption in C57BL/6J mice. Microarray analysis revealed that changes in gene expression occurred predominantly after one week, i.e. during the initial escalation of alcohol intake. One gene that stood out from our analysis was the adapter protein 14-3-3ζ, which was up-regulated during the transition from low to high alcohol intake. Independent qPCR analysis confirmed the up-regulation of amygdala 14-3-3ζ during the escalation of alcohol intake. Subsequently, we found that local knockdown of 14-3-3ζ in the amygdala, using RNA interference, dramatically augmented alcohol intake. In addition, knockdown of amygdala 14-3-3ζ promoted the development of inflexible alcohol drinking, as apparent from insensitivity to quinine adulteration of alcohol. This study identifies amygdala 14-3-3ζ as a novel key modulator that is engaged during escalation of alcohol use

Aggressive treatment with noninvasive ventilation for mild acute hypoxemic respiratory failure after cardiovascular surgery: Retrospective observational study

<p>Abstract</p> <p>Background</p> <p>Acute hypoxemic respiratory failure (AHRF) is one of the most serious complications after cardiovascular surgery. It remains unclear whether noninvasive ventilation (NIV) has potential as an effective therapy for AHRF after cardiovascular surgery, although many reports have described the use of NIV for AHRF after extubation. The aim of this study was to investigate the effectiveness of NIV in the early stage of mild AHRF after cardiovascular surgery.</p> <p>Methods</p> <p>We retrospectively analyzed all patients admitted to the intensive care unit after cardiovascular surgery, whose oxygenation transfer (PaO₂/FIO₂) deteriorated mildly after extubation, and in whom NIV was initiated. A two-way analysis of variance and the Bonferroni multiple comparisons procedure, the Mann–Whitney test, Fisher’s exact test or the <it>χ</it>^<it>2</it>test was performed.</p> <p>Results</p> <p>A total of 94 patients with AHRF received NIV, of whom 89 patients (94%) successfully avoided endotracheal intubation (successful group) and five patients required reintubation (reintubation group). All patients, including the reintubated patients, were successfully weaned from mechanical ventilation and discharged from the intensive care unit. In the successful group, PaO₂/FIO₂ improved and the respiratory rate decreased significantly within 1 h after the start of NIV, and the improvement in PaO₂/FIO₂ remained during the whole NIV period.</p> <p>Conclusion</p> <p>We conclude that NIV is beneficial for mild AHRF after cardiovascular surgery when it is started within 3 h after mild deterioration of PaO₂/FIO₂. We also think that it is important not to hesitate before performing reintubation when NIV is judged to be ineffective.</p