Adjunctive mild hypothermia therapy to primary percutaneous coronary intervention in patients with ST segment elevation myocardial infarction complicated with cardiogenic shock: A pilot feasibility study

Background: Despite successful primary reperfusion therapy, patients may develop large myocardial infarction related in part to reperfusion injury. Induction of mild therapeutic hy­pothermia (TH) applied in patients has demonstrated beneficial effect in reducing reperfusion injury. The aim of the study was to evaluate the feasibility and safety of adjunctive mild TH to primary percutaneous coronary intervention (PPCI) in patients with acute ST elevation myocardial infarction (STEMI) complicated with cardiogenic shock (CS). Methods: We conducted a prospective single center, open label, historical control study. Pa­tients presenting with STEMI and CS despite maximal support therapy scheduled for PPCI were included. Death was defined as primary endpoint. Secondary outcomes included: TH adverse effect — such as fever, refractory hypotension and arrhythmias, infarct size measured by area under the curve of biomarkers. Results: Eight consecutive patients were prospectively enrolled (TH group). Thirteen clinically similar patients identified from our database, admitted over 2 years, comprised the historical control group (control group). In the hypothermia group, the mortality was 50% compared with 46% in the control group. There was no difference in the secondary outcomes. Conclusions: TH as adjunctive therapy in STEMI patients complicated with CS is feasible and safe. Based on these preliminary observations there appears to be no significant clinical advantage to this form of therapy

Environmental Enrichment Preceding Early Adulthood Methylphenidate Treatment Leads to Long Term Increase of Corticosterone and Testosterone in the Rat

Attention-deficit/hyperactivity disorder (ADD/ADHD) has been emerging as a world-wide psychiatric disorder. There appears to be an increasing rate of stimulant drug abuse, specifically methylphenidate (MPH) which is the most common treatment for ADHD, among individuals who do not meet the criteria for ADHD and particularly for cognitive enhancement among university students. However, the long term effects of exposure to MPH are unknown. Thus, in light of a developmental approach in humans, we aimed to test the effects of adolescence exposure to enriched environment (EE) followed by MPH administration during early adulthood, on reactions to stress in adulthood. Specifically, at approximate adolescence [post natal days (PND) 30–60] rats were reared in EE and were treated with MPH during early adulthood (PND 60–90). Adult (PND 90–92) rats were exposed to mild stress and starting at PND 110, the behavioral and endocrine effects of the combined drug and environmental conditions were assessed. Following adolescence EE, long term exposure to MPH led to decreased locomotor activity and increased sucrose preference. EE had a beneficial effect on PPI (attentive abilities), which was impaired by long term exposure to MPH. Finally, the interaction between EE and, exposure to MPH led to long-term elevated corticosterone and testosterone levels. In view of the marked increase in MPH consumption over the past decade, vigilance is crucial in order to prevent potential drug abuse and its long term detrimental consequences

The effect of MPH on PPI.

<p>Significant differences in PPI scores were observed. EE led to the highest PPI compared with all groups (<i>P</i><0.0001). Following MPH treatment, the EES group showed higher PPI compared with control (<i>P</i><0.0001) and stress (<i>P</i><0.001) groups. A panel of representative traces demonstrate the differences in maximal response inhibition (at pre-intensity of 69 dB) of all four groups, with and without MPH. n = 9 to 10 per group.</p

The effect of MPH on locomotor activity.

<p>A significant difference in distance (A) and velocity (B) were detected between the groups in the open field test. Rats exposed to MPH following EE showed the lowest distance and velocity. These effects were not related to differences in body weight (C). MPH treatment significantly increased freezing duration (D) compared to saline. Following EE, MPH led to the highest freezing duration. * <i>P</i><0.0001 versus control; ** a: <i>P</i><0.022, b: <i>P</i><0.008, c: <i>P</i><0.0001 versus EE saline; n = 9 to 10 per group.</p

The effect of MPH on CORT and TST levels.

<p>A significant difference in CORT (A) and TST (B) levels was observed. MPH treatment significantly increased CORT level in the EE and EES groups (* P<0.0001; ** P<0.002 compared with their respective controls). TST level was similar across all groups, while MPH treatment increased TST level in both EE and EES groups (* P<0.001; ** P<0.012 compared with their counterpart controls). n = 9 to 10 per group.</p

The effect of MPH on sucrose preference test.

<p>Considerable variation in sucrose intake was observed between the groups. While significant long term anhedonia was detected in the EE group, MPH treatment following EE significantly recovers this effect. * <i>P</i><0.019 versus control; ** <i>P</i><0.0001 versus EE saline; n = 9 to 10 per group.</p

Schematic diagram of experimental design and procedures.

<p>Schematic diagram of experimental design and procedures.</p

Major depressive disorder and bistability in an HPA-CNS toggle switch.

Major depressive disorder (MDD) is the most common psychiatric disorder. It has a complex and heterogeneous etiology. Most treatments take weeks to show effects and work well only for a fraction of the patients. Thus, new concepts are needed to understand MDD and its dynamics. One of the strong correlates of MDD is increased activity and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis which produces the stress hormone cortisol. Existing mathematical models of the HPA axis describe its operation on the scale of hours, and thus are unable to explore the dynamic on the scale of weeks that characterizes many aspects of MDD. Here, we propose a mathematical model of MDD on the scale of weeks, a timescale provided by the growth of the HPA hormone glands under control of HPA hormones. We add to this the mutual inhibition of the HPA axis and the hippocampus and other regions of the central nervous system (CNS) that forms a toggle switch. The model shows bistability between euthymic and depressed states, with a slow timescale of weeks in its dynamics. It explains why prolonged but not acute stress can trigger a self-sustaining depressive episode that persists even after the stress is removed. The model explains the weeks timescale for drugs to take effect, as well as the dysregulation of the HPA axis in MDD, based on gland mass changes. This understanding of MDD dynamics may help to guide strategies for treatment

Dog training alleviates PTSD symptomatology by emotional and attentional regulation

Background: Post-Traumatic Stress Disorder (PTSD) symptoms include re-experiencing, avoidance, hyperarousal, and cognitive deficits, reflecting both emotional and cognitive dysregulation. In recent years, non-pharmacological approaches and specifically animal-assisted therapy have been shown to be beneficial for a variety of disorders such as Attention-Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, and PTSD. However, little is mentioned in the literature about the reciprocal effects of the animal–human interaction. Objective: To evaluate the effects of a one-year dog training programme on PTSD symptomatology in youngsters with PTSD and on dogs’ behaviour. Methods: Fifty-three adolescents, previously exposed to interpersonal trauma, were clinically diagnosed with PTSD and assigned to a dog-training programme group (n = 30) and a control group (n = 23) that engaged in other training programmes (e.g. cooking, hairstyling, etc.). Both groups were evaluated at baseline and following 12-months by The Clinician-Administered PTSD Scale for DSM-5 in Children and Adolescents (CAPS-CA-5) and Beck-Depression Inventory (BDI). Additionally, we physiologically measured both emotional and attention dysregulation. Results: Post-12-months training, a significant alleviation of PTSD symptomatology accompanied by lower depression severity was observed in the dog-training group, compared with a insignificant recovery in the control group. Furthermore, improved emotional and attentional regulation was observed in the dog-training group. Measuring the dogs’ behaviour revealed increased anxiety and decreased selective attention performance, which was inversely correlated with the beneficial effects observed in the dog-training programme group. Conclusions: Our findings emphasize the role of emotional and attentional regulations on the dog–handler interface, as evidence-based support for the beneficial effects of the dog-training programme, as either a non-pharmacological intervention or as complementary to anti-depressants treatment of PTSD. Though pharmacological treatments increase the patients’ well-being by treating certain PTSD symptoms, our suggested dog-training programme seems to influence the PTSD diagnostic status, thus may be implemented in civilians and veterans with PTSD