Winning Fights Induces Hyperaggression via the Action of the Biogenic Amine Octopamine in Crickets

Winning an agonistic interaction against a conspecific is known to heighten aggressiveness, but the underlying events and mechanism are poorly understood. We quantified the effect of experiencing successive wins on aggression in adult male crickets (Gryllus bimaculatus) by staging knockout tournaments and investigated its dependence on biogenic amines by treatment with amine receptor antagonists. For an inter-fight interval of 5 min, fights between winners escalated to higher levels of aggression and lasted significantly longer than the preceding round. This winner effect is transient, and no longer evident for an inter-fight interval of 20 min, indicating that it does not result from selecting individuals that were hyper-aggressive from the outset. A winner effect was also evident in crickets that experienced wins without physical exertion, or that engaged in fights that were interrupted before a win was experienced. Finally, the winner effect was abolished by prior treatment with epinastine, a highly selective octopamine receptor blocker, but not by propranolol, a ß-adrenergic receptor antagonist, nor by yohimbine, an insect tyramine receptor blocker nor by fluphenazine an insect dopamine-receptor blocker. Taken together our study in the cricket indicates that the physical exertion of fighting, together with some rewarding aspect of the actual winning experience, leads to a transient increase in aggressive motivation via activation of the octopaminergic system, the invertebrate equivalent to the adrenergic system of vertebrates

Haploinsufficiency of the E3 Ubiquitin Ligase C-Terminus of Heat Shock Cognate 70 Interacting Protein (CHIP) Produces Specific Behavioral Impairments

The multifunctional E3 ubiquitin ligase CHIP is an essential interacting partner of HSP70, which together promote the proteasomal degradation of client proteins. Acute CHIP overexpression provides neuroprotection against neurotoxic mitochondrial stress, glucocorticoids, and accumulation of toxic amyloid fragments, as well as genetic mutations in other E3 ligases, which have been shown to result in familial Parkinson's disease. These studies have created a great deal of interest in understanding CHIP activity, expression and modulation. While CHIP knockout mice have the potential to provide essential insights into the molecular control of cell fate and survival, the animals have been difficult to characterize in vivo due to severe phenotypic and behavioral dysfunction, which have thus far been poorly characterized. Therefore, in the present study we conducted a battery of neurobehavioral and physiological assays of adult CHIP heterozygotic (HET) mutant mice to provide a better understanding of the functional consequence of CHIP deficiency. We found that CHIP HET mice had normal body and brain weight, body temperature, muscle tone and breathing patterns, but do have a significant elevation in baseline heart rate. Meanwhile basic behavioral screens of sensory, motor, emotional and cognitive functions were normative. We observed no alterations in performance in the elevated plus maze, light-dark preference and tail suspension assays, or two simple cognitive tasks: novel object recognition and spontaneous alternation in a Y maze. Significant deficits were found, however, when CHIP HET mice performed wire hang, inverted screen, wire maneuver, and open field tasks. Taken together, our data indicate a clear subset of behaviors that are altered at baseline in CHIP deficient animals, which will further guide whole animal studies of the effects of CHIP dysregulation on cardiac function, brain circuitry and function, and responsiveness to environmental and cellular stress

Physiological responses during ascent to high altitude and the incidence of acute mountain sickness.

Acute mountain sickness (AMS) occurs when there is failure of acclimatisation to high altitude. The aim of this study was to describe the relationship between physiological variables and the incidence of AMS during ascent to 5300 m. A total of 332 lowland-dwelling volunteers followed an identical ascent profile on staggered treks. Self-reported symptoms of AMS were recorded daily using the Lake Louise score (mild 3-4; moderate-severe ≥5), alongside measurements of physiological variables (heart rate, respiratory rate (RR), peripheral oxygen saturation (SpO2 ) and blood pressure) before and after a standardised Xtreme Everest Step-Test (XEST). The overall occurrence of AMS among participants was 73.5% (23.2% mild, 50.3% moderate-severe). There was no difference in gender, age, previous AMS, weight or body mass index between participants who developed AMS and those who did not. Participants who had not previously ascended >5000 m were more likely to get moderate-to-severe AMS. Participants who suffered moderate-to-severe AMS had a lower resting SpO2 at 3500 m (88.5 vs. 89.6%, p = 0.02), while participants who suffered mild or moderate-to-severe AMS had a lower end-exercise SpO2 at 3500 m (82.2 vs. 83.8%, p = 0.027; 81.5 vs. 83.8%, p 5000 m (OR 2.740, p-value 0.003) predicted the development of moderate-to-severe AMS. The Xtreme Everest Step-Test offers a simple, reproducible field test to help predict AMS, albeit with relatively limited predictive precision

High PEEP in ARDS: quantitative evaluation between improved oxygenation and decreased oxygen delivery

Background: Positive end-expiratory pressure (PEEP) is widely used to improve oxygenation and prevent alveolar collapse in mechanically ventilated patients with the acute respiratory distress syndrome (ARDS). While PEEP predictably improves arterial oxygenation, high PEEP strategies have demonstrated equivocal improvements in ARDS mortality. The effect of PEEP on tissue oxygen delivery is poorly understood and is difficult to quantify or investigate in the clinical environment. Methods: We investigated the effects of PEEP on tissue oxygen delivery in ARDS using a novel, high-fidelity, computational model with highly integrated respiratory and cardiovascular systems. The model was configured to replicate published clinical trial data on the responses of individual ARDS patients to changes in PEEP. These virtual patients were subjected to increasing PEEP levels during a lung-protective ventilation strategy (0 - 20 cmH2O). Measured variables included arterial oxygenation, cardiac output, peripheral oxygen delivery and alveolar strain. Results: As PEEP increased, tissue oxygen delivery decreased in all subjects (mean reduction 25% at 20 cmH2O PEEP), despite an increase in arterial oxygen tension (mean increase 6.7 kPa, at 20 cmH2O PEEP). Changes in arterial oxygenation and tissue oxygen delivery differed between subjects, but showed a consistent pattern. Static and dynamic alveolar strain decreased in all patients as PEEP increased. Conclusions: Incremental PEEP in ARDS appears to protect alveoli and improve arterial oxygenation, but also appears to significantly impair tissue oxygen delivery due to reduced cardiac output. We propose why this trade-off may explain the poor improvements in mortality associated with high PEEP ventilation strategies

Thermal ablation system using high intensity focused ultrasound (HIFU) and guided by MRI

Part of AIP Conference Proceedings, Volume 1113In this paper magnetic resonance imaging (MRI) is investigated for monitoring lesions created by high intensity focused ultrasound (HIFU) in kidney, liver and brain in vitro and in vivo. Spherically focused transducers of 4 cm diameter, focusing at 10 cm and operating at 1 and 4 MHz were used. An MRI compatible positioning device was developed in order to scan the HIFU transducer. The MRI compatibility of the system was successfully demonstrated in a clinical high-field MRI scanner. The ability of the positioning device to accurately move the transducer thus creating discrete and overlapping lesions in biological tissue was tested successfully. A simple, cost effective, portable positioning device has been developed which can be used in virtually any clinical MRI scanner since it can be sited on the scanner's table. The propagation of HIFU can use either a lateral or superior-inferior approach. Both T1-w FSE and T2-w FSE imaged successfully lesions in kidney and liver. T1-w FSE and T2-w FSE and FLAIR shows better anatomical details in brain than T1-w FSE, but with T1-w FSE the contrast between lesion and brain is higher for both thermal and bubbly lesion. With this system we were able to create large lesions (by producing overlapping lesions). The length of the lesions in vivo brain was much higher than the length in vitro, proving that the penetration in the in vitro brain is limited by reflection due to trapped bubbles in the blood vessels. © 2009 American Institute of Physics

Free and total cortisol levels as predictors of severity and outcome in community-acquired pneumonia.

RATIONALE: High cortisol levels are of prognostic value in sepsis. The predictive value of cortisol in pneumonia is unknown. Routinely available assays measure serum total cortisol (TC) and not free cortisol (FC). Whether FC concentrations better reflect outcome is uncertain. OBJECTIVES: To investigate the predictive value of TC and FC in community-acquired pneumonia (CAP). METHODS: Preplanned subanalysis of a prospective intervention study in 278 patients presenting to the emergency department with CAP. MEASUREMENTS AND MAIN RESULTS: TC, FC, procalcitonin, C-reactive protein, leukocytes, clinical variables, and the pneumonia severity index (PSI) were measured. The major outcome measures were PSI and survival. TC and FC, but not C-reactive protein or leukocytes, increased with increasing severity of CAP according to the PSI (P < 0.001). TC and FC levels on presentation in patients who died during follow-up were significantly higher as compared with levels in survivors. In a receiver operating characteristic analysis to predict survival, the area under the receiver operating characteristic curve (AUC) was 0.76 (95% confidence interval, 0.70-0.81) for TC and 0.69 (0.63-0.74) for FC. This was similar to the AUC of the PSI (0.76 [0.70-0.81]), and better as compared with C-reactive protein, procalcitonin, or leukocytes. In univariate analysis, only TC, FC, and the PSI were predictors of death. In multivariate analysis, the predictive potential of TC equaled the prognostic power of PSI points. CONCLUSIONS: Cortisol levels are predictors of severity and outcome in CAP to a similar extent to the PSI, and are better than routinely measured laboratory parameters. In CAP, the prognostic accuracy of FC is not superior to TC. Clinical trial registered with www.controlled-trials.com (ISRCTN04176397)

Measurement of serum free cortisol shows discordant responsivity to stress and dynamic evaluation.

CONTEXT: Routinely available assays of adrenal function measure serum total cortisol (TC) and not the biologically active free cortisol (FC). However, there are few data on FC levels during surgical stress and in response to standard pharmacological tests. OBJECTIVE: Our objective was to evaluate TC and FC levels in different states of physical stress. DESIGN AND SETTING: We conducted a prospective observational study in a university hospital. PARTICIPANTS AND MAIN OUTCOME MEASURES: We measured TC and FC levels in 64 patients: group A, 17 healthy controls without stress; group B, 23 medical patients with moderate stress; and group C, 24 surgical patients undergoing coronary bypass grafting. Cortisol levels in group C were measured basally and at several time points thereafter and were compared with responsivity to a pharmacological dose of ACTH. FC was measured using equilibrium dialysis. RESULTS: In group C patients after extubation, the relative increase above basal FC was higher than the increase in TC levels (399 +/- 266 vs. 247 +/- 132% of initial values, respectively; mean +/- sd; P = 0.02) and then fell more markedly, FC levels falling to 67 +/- 49% and TC levels to 79 +/- 36% (P = 0.04). After ACTH stimulation, TC levels increased to 680 +/- 168 nmol/liter, which was similar to the increase with major stress (811 +/- 268 nmol/liter). In contrast, FC levels increased to 55 +/- 16 nmol/liter after ACTH stimulation but significantly greater with surgical stress to 108 +/- 56 nmol/liter (P < 0.001). CONCLUSION: The more pronounced increase in FC seen during stress as compared with the ACTH test suggests that this test does not adequately anticipate the FC levels needed during severe stress