Modulation of microglial activation by antidepressants.

BACKGROUND: Recent studies have suggested that microglial activation plays a key role in the pathogenesis of depression. In fact, neuroinflammation is associated with a phenotypic change of microglia, consisting of morphological differences, increased release of cytokines and oxidative stress products, which may contribute to the development and maintenance of depression. Antidepressants, including selective serotonin re-uptake inhibitors and serotonin-norepinephrine reuptake inhibitors, have been shown to act on the immune and oxidative stress mechanisms commonly found to be disrupted in depression. Thus, the inhibition of microglial activation may be one of the mechanisms through which they exert an antidepressant action. AIM: This is the first review summarising in vitro and ex vivo studies investigating the effects of different classes of antidepressants on microglia activation, by examining cellular changes and/or via measuring the production of immune and/or oxidative stress signalling molecules, in microglia models of neuroinflammation with either lipopolysaccharide (LPS) or cytokines. A total of 23 studies were identified, 18 using LPS stimulation and 5 using cytokines stimulation. RESULTS: Overall, the studies show that antidepressants, such as selective serotonin re-uptake inhibitors, serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors and tricyclic antidepressants prevented microglial activation, including reduced microglial reactivity and decreased immune and oxidative stress products, in both models. However, specific antidepressants, such as bupropion and agomelatine did not prevent interferon-gamma (IFN-γ)-induced microglial activation; and for other antidepressants, including phenelzine, venlafaxine and sertraline, the results of different studies were inconsistent. CONCLUSIONS: Overall, results summarised in this review support the hypothesis that the action of at least certain classes of antidepressants may involve regulation of microglial activation, especially when in presence of increased levels of inflammation.

Should positive end-expiratory pressure be used during elective general anaesthesia with supraglottic airway devices?

Anaesthetists' use of positive end-expiratory pressure during elective general anaesthesia via supraglottic airway devices varies. Positive end-expiratory pressure may help to maintain oxygenation and prevent atelectasis, but could worsen the risk of air leak, gastric insufflation and catastrophic aspiration.

Impact of Simulation Training on Undergraduate Clinical Decision-making in Emergencies: A Non-blinded, Single-centre, Randomised Pilot Study.

Introduction There is an increasing evidence base for the use of simulation-based medical education. Simulation is superior to more didactic methods for teaching a range of technical and non-technical skills, and students report they often derive more educational value from it compared with other teaching methods. There is currently limited evidence that simulation training improves clinical decision-making and, therefore, this pilot study sought to explore this further. Methods Students were randomised to take part in either five classroom tutorials and simulation training sessions or five classroom tutorials and an online e-learning module. On completion of the teaching, students all undertook an unseen assessment scenario (managing a simulated patient with anaphylaxis), where they were scored using a weighted marking scheme. The time taken to make decisions and student-reported confidence in decisions were also measured. Results 14/14 simulation-group participants and 12/14 e-learning-group participants completed the post-learning assessment. The simulation group identified anaphylaxis and gave adrenaline more quickly (p 0.008 and 0.005, respectively), and this cohort was more confident in making the diagnosis (p 0.044). There was no statistically significant difference between weighted global assessment scores for each group (p 0.705). The e-learning group called for help more quickly (p.0.049), although fewer students in this group called for help (five vs. nine). There was no statistical difference in confidence in decisions to administer adrenaline or call for help (p 0.539 and 0.364 respectively). Conclusions Participants who undertook simulation training were able to more confidently and quickly identify the diagnosis and initiate emergency treatment. However, there was not a statistically significant difference between groups using an overall weighted score. Using simulation to train students to perform better in emergencies and improve their decision-making shows promise but a further quantitative study is required.

Cardiac hemodynamics of the rainbow trout (Oncorhynchus mykiss) using simultaneous Doppler echocardiography and electrocardiography.

Using Doppler echocardiography and electrocardiography, we characterized cardiac hemodynamics, timing, and electromechanical function, and examined the effects of ventricular hypertrophy on systolic function in anesthetized rainbow trout. Atrial filling (D(SA)), ventricular filling (D(AV)), and ventricular ejection (D(VB)) accounted for 40-77, 13-27, and 22-41% of the cardiac cycle, respectively. Ventricular ejection occurred entirely during atrial filling and ended by the time the QT interval was 80% (SD=9%) completed. Sinoatrial (SA) flow was of longer duration (0.53+/-0.08 sec, mean+/-SD) and lower velocity (32+/-8 cm sec(-1)) than corresponding atrioventricular (AV, 0.19+/-0.02 sec; 87+/-8 cm sec(-1)) and ventriculobulbar (VB, 0.30+/-0.05 sec; 63+/-20 cm sec(-1)) values. Despite a wide range of heart masses, atrioventricular and VB valve dimensions were identical ( approximately 5.5 mm(2)). Ventricle mass (M(V)), but not relative ventricle mass (RVM), and cardiac cycle length were positively correlated (r(2)=0.57, P<0.001); thus, all time-dependent electrical/mechanical measures of cardiac function were significantly related to M(V), but not RVM. All rate-corrected (c) electromechanical event durations (except cD(SA)) and the systolic function index (cPEP (pre-ejection period)/D(VB)) were independent of RVM, suggesting the maintenance of cardiac functional capabilities across maturation stages (males) and different ventricle sizes (males and females). In summary, we define fundamental electrical and mechanical properties of the in vivo teleost myocardium under anesthesia, and report the maintenance of systolic function over a wide range of heart sizes for both sexes and maturation state of males. We also suggest that the short duration of ventricular emptying relative to the QT interval may provide a novel mechanism to adjust stroke volume and cardiac output in teleosts.