An investigation of cardiac vagal tone over time and its relation to vigilance performance: a growth curve modeling approach.

Introduction: Research over the last couple of decades has demonstrated a relationship between psychophysiological measures, specifically cardiac functions, and cognitive performance. Regulation of the cardiac system under parasympathetic control is commonly referred to as cardiac vagal tone and is associated with the regulation of cognitive and socioemotional states. The goal of the current study was to capture the dynamic relationship between cardiac vagal tone and performance in a vigilance task. Method/Results: We implemented a longitudinal growth curve modeling approach which unveiled a relationship between cardiac vagal tone and vigilance that was non-monotonic and dependent upon each person. Discussion: The findings suggest that cardiac vagal tone may be a process-based physiological measure that further explains how the vigilance decrement manifests over time and differs across individuals. This contributes to our understanding of vigilance by modeling individual differences in cardiac vagal tone changes that occur over the course of the vigilance task.

Can the Biophilia Hypothesis Be Applied to Long-Duration Human Space Flight? A Mini-Review.

The International Space Station (ISS) has around 3-5 crew members on-board at all times, and they normally stay on the ISS for about 5-7months in duration. Since March 2020, 170 long-duration space missions have occurred on the ISS. Thus, long-duration space missions are an integral part of space exploration and will only continue to expand in duration as missions to the Moon and Mars are on the horizon. However, long-duration space missions present several challenges to human crew members. Most of these challenges have been associated with physiological adaptation to microgravity, including motion sickness, muscle atrophy, and cardiovascular deconditioning. While not as well-studied, another major factor to consider when planning long-duration space missions is the psychological impact of the environment on the astronauts. Astronauts living in space will be unable to access natural landscapes and other environments found to have restorative effects on psychological stress and overall well-being. On top of being unable to access these restorative natural environments, astronauts will also be exposed to the stressful, unfamiliar environment of space. The purpose of this mini-review is to first summarize the literature related to stressors associated with space. Next, an overview of the large breadth of literature on the biophilia hypothesis and restorative environments will be provided, as these may serve as relatively simple and cost-effective solutions to mitigate the stress faced during long-duration space missions. Lastly, considerations related to the design of such environments in a space capsule as well as future directions will be presented.

Restoring Attentional Resources With Nature: A Replication Study of Berto's (2005) Paradigm Including Commentary From Dr. Rita Berto.

OBJECTIVE: The aim of this study is to replicate Berto's (2005) heavily cited work on attention restoration. BACKGROUND: Nature interventions have gained increased interest for improving performance of attentionally demanding tasks. Berto (2005) indicated that viewing digital nature images could improve performance on a subsequent response inhibition task, the sustained attention to response task (SART). However, experimental design and statistical concerns about her experiments as well as failure to support her findings across multiple unpublished studies in our laboratory provided rationale for this replication study. METHOD: Twenty participants were each assigned to one of three digital image conditions: nature, urban, and control. Participants performed the SART before and after digital image exposure. RESULTS: SART performance metrics (total correct target responses, mean response time, and transformed d') were analyzed using 2 (SART) × 3 (image interventions) mixed design ANOVAs. The results failed to replicate Berto (2005). CONCLUSION: Possible reasons for not replicating Berto (2005) are discussed, including (1) sample differences, (2) different testing environments and procedures, (3) insufficient attentional depletion, and (4) individual differences. APPLICATIONS: Research needs to determine the effectiveness of such interventions, the specific attention tasks that might benefit, and the individual difference variables relevant for attention restoration.

The Abbreviated Vigilance Task and Its Attentional Contributors.

OBJECTIVE: To measure contributing attentional processes, particularly that of executive attention, to two iterations of the abbreviated vigilance task. BACKGROUND: Joel Warm was at the forefront of vigilance research for decades, and resource theory is currently the dominant explanation for the vigilance decrement. The underlying mechanisms contributing to both overall performance and the decrement are only partly understood. METHOD: Seventy-eight participants answered questionnaires about their attentional skills and stress state, performed the Attention Network Test and two blocks of the 12-min abbreviated vigilance task, with a brief break between the two vigils during which they viewed images intended to affect performance. Changes in oxygenated hemoglobin were measured with functional near-infrared imaging. RESULTS: Expected patterns were observed for both iterations of the abbreviated vigilance task, with performance declining after the first 2 min. Manipulations intended to evaluate whether executive processes contributed to vigilance performance failed to observe an effect. Other factors, particularly orienting and alerting attentional networks, task engagement, and subclinical ADHD symptomology were associated with performance. Significant factors for the first and second vigilance blocks were different. CONCLUSION: We suggest that (a) cognitive control is not a predominant factor, at least for the abbreviated vigilance task, and (b) attentional mechanisms and stress states affecting performance on the abbreviated vigilance task change over time. APPLICATION: Potential applications of this research include the use of breaks for sustained attention tasks involving high sensory load, and implications for the use of the abbreviated vigilance task as a proxy for general vigilance processes.

Assessment of Performance Carryover Effects Due to Successive Exposure to Different Lateral Camera Rotations in a Laparoscopic Training Environment.

Objective The aim of this study was to assess performance carryover effects associated with different successive lateral camera rotations in the laparoscopic training environment. Background Laparoscopy requires surgeons to adapt to disruptions of visuomotor mapping. A gradual adaptation process is hypothesized to be effective up to a given rotation threshold; this threshold may have performance implications for successive exposure to different lateral camera rotations. Method Two experiments utilized a laparoscopic training task. Experiment 1 exposed novices to a subsequent rotation that was either 45° larger than one of the initial rotations of 45°, 75°, 105°, and 135° or 45° smaller than one of the initial rotations of 90°, 120°, 150°, and 180°. Experiment 2 exposed novices to either stepwise increasing rotations (0° to 180°) or stepwise decreasing rotations (180° to 0°). Results Regarding Experiment 1, performance generally improved for subsequent rotations that were 45° larger than the initial rotation, except for one condition (initial rotation, 105°; subsequent rotation, 150°). Performance generally improved for subsequent rotations that were 45° smaller than the initial rotation, except for one condition (initial rotation, 120°; subsequent rotation, 75°). Experiment 2 indicated worst performance at 120° for the increasing and decreasing conditions. This finding suggests an identical threshold for increasing and decreasing rotations, which is inconsistent with Experiment 1 results. Conclusion Improved performance due to carryover effects from successive exposure to lateral camera rotations in the laparoscopic training environment is contingent on the specific camera rotations. Application Supplementary laparoscopic training might be needed for surgeries that entail certain successive lateral camera rotations.

Meta-analysis of the COMT Val158Met polymorphism in major depressive disorder: the role of gender.

OBJECTIVES: Many studies have reported an association of the COMT Val158Met polymorphism and major depressive disorder (MDD), although with conflicting results. The role of gender is a possible modulator. To overcome the problem of poor sample size detecting genes of small effect, we perform a meta-analysis of the current literature, investigating the influence of the COMT Val158Met polymorphism on the pathogenesis of MDD, with a major focus on the effect of gender. METHODS: Out of 977 retrieved articles, 21 included case-control studies allowed the analysis of 9005 patients with MDD and 12,095 controls. Allelic and genotypic pooled odds ratios (OR) were calculated for the total sample and gender-subgroups. RESULTS: In the absence of publication bias, allelic and genotypic analyses showed no significant association in the total sample, as well as in gender-specific subgroups. Sensitivity analysis did not alter the ORs. CONCLUSIONS: The results imply a complex nature of the genotype × phenotype interaction. Further studies of the COMT gene or the locus remain to be justified given the important positional and functional relevance and the plethora of gender-specific findings. A possible way to further dissect this topic is shifting the focus to gene-based or genome-wide analyses of intermediate phenotypes.

Urology residents experience comparable workload profiles when performing live porcine nephrectomies and robotic surgery virtual reality training modules.

In pursuit of improving the quality of residents' education, the Southeastern Section of the American Urological Association (SES AUA) hosts an annual robotic training course for its residents. The workshop involves performing a robotic live porcine nephrectomy as well as virtual reality robotic training modules. The aim of this study was to evaluate workload levels of urology residents when performing a live porcine nephrectomy and the virtual reality robotic surgery training modules employed during this workshop. Twenty-one residents from 14 SES AUA programs participated in 2015. On the first-day residents were taught with didactic lectures by faculty. On the second day, trainees were divided into two groups. Half were asked to perform training modules of the Mimic da Vinci-Trainer (MdVT, Mimic Technologies, Inc., Seattle, WA, USA) for 4 h, while the other half performed nephrectomy procedures on a live porcine model using the da Vinci Si robot (Intuitive Surgical Inc., Sunnyvale, CA, USA). After the first 4 h the groups changed places for another 4-h session. All trainees were asked to complete the NASA-TLX 1-page questionnaire following both the MdVT simulation and live animal model sessions. A significant interface and TLX interaction was observed. The interface by TLX interaction was further analyzed to determine whether the scores of each of the six TLX scales varied across the two interfaces. The means of the TLX scores observed at the two interfaces were similar. The only significant difference was observed for frustration, which was significantly higher at the simulation than the animal model, t (20) = 4.12, p = 0.001. This could be due to trainees' familiarity with live anatomical structures over skill set simulations which remain a real challenge to novice surgeons. Another reason might be that the simulator provides performance metrics for specific performance traits as well as composite scores for entire exercises. Novice trainees experienced substantial mental workload while performing tasks on both the simulator and the live animal model during the robotics course. The NASA-TLX profiles demonstrated that the live animal model and the MdVT were similar in difficulty, as indicated by their comparable workload profiles.

Sideways camera rotations of 90° and 135° result in poorer performance of laparoscopic tasks for novices.

OBJECTIVE: The aim of this study was to determine the impact of sideways visuomotor rotations between 0° and 180° on novice performance in a laparoscopic simulator. BACKGROUND: The laparoscopic surgical environment often involves visuomotor rotations because the laparoscope may be placed to the surgeon's side. Basic research by Cunningham indicated that visuomotor rotations between 90° and 135° result in peak performance decrements. Research by Ames and colleagues failed to replicate Cunningham's results in the laparoscopic environment, possibly due to (a) confounds from carryover effects or (b) use of an alternative laparoscopic training task rather than the straight-line pointing task used by Cunningham. Two experiments were conducted to determine if Cunningham's results generalize to the laparoscopic environment when controlling for carryover effects for a three-dimensional "straight-line" pointing task (Experiment 1) and a laparoscopic training task (Experiment 2). METHOD: In Experiments 1 and 2, participants were assigned to one of five visuomotor rotations: 0°, 45°, 90°, 135°, or 180°. Utilizing a laparoscopic simulator, participants performed either a three-dimensional pointing task (Experiment 1) or a peg transfer task (Experiment 2). RESULTS: In both experiments, visuomotor rotations of 90° or 135° resulted in the poorest performance. CONCLUSION: When controlling for carryover effects, Cunningham's results generalize to novices' performance of a pointing and a peg transfer task in the laparoscopic environment. APPLICATIONS: The results indicate that 90° and 135° sideways laparoscope placements may result in worse performance for novices in the laparoscopic environment, indicating potentially longer learning curves for these conditions in the laparoscopic as well as other teleoperation environments.

Mental stress experienced by first-year residents and expert surgeons with robotic and laparoscopic surgery interfaces.

Prior research has indicated that novices experienced a beneficial stress profile in the robotic surgery (da Vinci) training environment when compared to the laparoscopic surgery training environment. The objective of this study was to assess whether this finding generalizes to expert surgeons. Towards that end, first-year residents' and attending surgeons' performances and subjective stress experiences were assessed in a surgical training task that was performed with the da Vinci and laparoscopic surgery interfaces. This study indicated that both groups exhibited superior performance and lower stress with the da Vinci surgical system than the laparoscopic system. The results provide further support for the sensitivity of the Dundee Stress State Questionnaire in identifying different stress responses experienced by trainees and experts in the minimally invasive surgery environment.

The impact of visual scanning in the laparoscopic environment after engaging in strain coping.

OBJECTIVE: We aimed to determine whether visual scanning has a detrimental impact on the monitoring of critical signals and the performance of a concurrent laparoscopic training task after participants engaged in Hockey's strain coping. Strain coping refers to straining cognitive (attentional) resources joined with latent decrements (i.e., stress). BACKGROUND: DeLucia and Betts (2008) reported that monitoring critical signals degraded performance of a laparoscopic peg-reversal task compared with no monitoring. However, performance did not differ between displays in which critical signals were shown on split screens (less visual scanning) and separated displays (more visual scanning). We hypothesized that effects of scanning may occur after prolonged strain coping. METHOD: Using a between-subjects design, we had undergraduates perform a laparoscopic training task that induced strain coping. Then they performed a laparoscopic peg-reversal task while monitoring critical signals with a split-screen or separated display. We administered the NASA-Task Load Index (TLX) and Dundee Stress State Questionnaire (DSSQ) to assess strain coping. RESULTS: The TLX and DSSQ profiles indicated that participants engaged in strain coping. Monitoring critical signals resulted in slowed peg-reversal performance compared with no monitoring. Separated displays degraded critical-signal monitoring compared with split-screen displays. CONCLUSION: After novice observers experience strain coping, visual scanning can impair the detection of critical signals. APPLICATION: Results suggest that the design and arrangement of displays in the operating room must incorporate the attentional limitations of the surgeon. Designs that induce visual scanning may impair monitoring of critical information at least in novices. Presenting displays closely in space may be beneficial.

Mental workload and stress perceived by novice operators in the laparoscopic and robotic minimally invasive surgical interfaces.

BACKGROUND AND PURPOSE: High levels of mental workload and stress are experienced by surgeons in the laparoscopic environment. The da Vinci(®) surgical robot was developed to provide surgeons a more user-friendly interface while maintaining the patient benefits associated with laparoscopy. This study examined whether the da Vinci robot reduces mental workload and stress in novice medical students. A detailed understanding of trainees' mental workload and mental stress experiences can aid in the development of training programs that are aimed at facilitating the acquisition of laparoscopic and robotic surgery skills. MATERIALS AND METHODS: Fifteen novice first-year medical students performed a standard peg-transfer task at a laparoscopic simulator and the da Vinci Surgical System. Mental workload and stress were assessed with the Multiple Resources Questionnaire (MRQ) and the Dundee Stress State Questionnaire (DSSQ), respectively. RESULTS: Students' mental workload profiles were identical with the two surgical systems and replicated previous MRQ results reported with the laparoscopic system showing high levels of workload. Students experienced a better stress profile with the robotic system, however, when compared wih the laparoscopic system. CONCLUSION: Our study shows that novice medical students perceive less stress when working with the robotic surgical interface than with the laparoscopic surgery interface. The MRQ and the DSSQ are valuable tools for identifying mental workload and mental stress in the laparoscopic and robotic surgery environments. This information may be useful for facilitating the acquisition of laparoscopic and robotic surgery skills.

Using cognitive task analysis to identify critical decisions in the laparoscopic environment.

OBJECTIVE: The aim of this study was to identify the critical decisions surgeons need to make regarding laparoscopic surgery, the information these decisions are based on, the strategies employed by surgeons to reach their objectives, and the difficulties experienced by novices. BACKGROUND: Laparoscopic training focuses on the development of technical skills. However, successful surgical outcomes are also dependent on appropriate decisions made during surgery, which are influenced by critical cues and the use of appropriate strategies. Novices might not be as adept at cue detection and strategy use. METHOD: Participants were eight attending surgeons. The authors employed task-analytic techniques to identify critical decisions inherent in laparoscopy and the cues, strategies, and novice traps associated with these decisions. RESULTS: The authors used decision requirements tables to organize the data into the key decisions made during the preoperative, operative, and postoperative phases as well as the cues, strategies, and novice traps associated with these decisions. Key decisions identified for the preoperative phase included but were not limited to the decision of performing a laparoscopic versus open surgery, necessity to review the literature, practicing the procedure, and trocar placement. Some key decisions identified for the operative phase included converting to open surgery, performing angiograms, cutting tissue or organs, and reevaluation of the approach. Only one key decision was identified for the postoperative phrase: whether the surgeon's technique needs to be evaluated and revised. CONCLUSION: The laparoscopic environment requires complex decision making, and novices are prone to errors in their decisions. APPLICATION: The information elicited in this study is applicable to laparoscopic training.

Hands-free administration of subjective workload scales: acceptability in a surgical training environment.

INTRODUCTION: Subjective workload measures are usually administered in a visual-manual format, either electronically or by paper and pencil. However, vocal responses to spoken queries may sometimes be preferable, for example when experimental manipulations require continuous manual responding or when participants have certain sensory/motor impairments. In the present study, we evaluated the acceptability of the hands-free administration of two subjective workload questionnaires - the NASA Task Load Index (NASA-TLX) and the Multiple Resources Questionnaire (MRQ) - in a surgical training environment where manual responding is often constrained. METHOD: Sixty-four undergraduates performed fifteen 90-s trials of laparoscopic training tasks (five replications of 3 tasks - cannulation, ring transfer, and rope manipulation). Half of the participants provided workload ratings using a traditional paper-and-pencil version of the NASA-TLX and MRQ; the remainder used a vocal (hands-free) version of the questionnaires. A follow-up experiment extended the evaluation of the hands-free version to actual medical students in a Minimally Invasive Surgery (MIS) training facility. RESULTS: The NASA-TLX was scored in 2 ways - (1) the traditional procedure using participant-specific weights to combine its 6 subscales, and (2) a simplified procedure - the NASA Raw Task Load Index (NASA-RTLX) - using the unweighted mean of the subscale scores. Comparison of the scores obtained from the hands-free and written administration conditions yielded coefficients of equivalence of r=0.85 (NASA-TLX) and r=0.81 (NASA-RTLX). Equivalence estimates for the individual subscales ranged from r=0.78 ("mental demand") to r=0.31 ("effort"). Both administration formats and scoring methods were equally sensitive to task and repetition effects. For the MRQ, the coefficient of equivalence for the hands-free and written versions was r=0.96 when tested on undergraduates. However, the sensitivity of the hands-free MRQ to task demands (η(partial)(2)=0.138) was substantially less than that for the written version (η(partial)(2)=0.252). This potential shortcoming of the hands-free MRQ did not seem to generalize to medical students who showed robust task effects when using the hands-free MRQ (η(partial)(2)=0.396). A detailed analysis of the MRQ subscales also revealed differences that may be attributable to a "spillover" effect in which participants' judgments about the demands of completing the questionnaires contaminated their judgments about the primary surgical training tasks. CONCLUSION: Vocal versions of the NASA-TLX are acceptable alternatives to standard written formats when researchers wish to obtain global workload estimates. However, care should be used when interpreting the individual subscales if the object is to make comparisons between studies or conditions that use different administration modalities. For the MRQ, the vocal version was less sensitive to experimental manipulations than its written counterpart; however, when medical students rather than undergraduates used the vocal version, the instrument's sensitivity increased well beyond that obtained with any other combination of administration modality and instrument in this study. Thus, the vocal version of the MRQ may be an acceptable workload assessment technique for selected populations, and it may even be a suitable substitute for the NASA-TLX.

Chronic inhibition of phosphodiesterase 5 does not prevent pressure-overload-induced right-ventricular remodelling.

AIMS: Inhibition of phosphodiesterase 5 (PDE5) decreases pulmonary pressure and improves symptoms in patients with pulmonary arterial hypertension. It is unclear however, whether inhibition of PDE5 can prevent myocardial remodelling during right-ventricular pressure overload. METHODS AND RESULTS: Right-ventricular pressure overload was produced in male rats in a pulmonary hypertension model (monocrotaline 60 mg/kg s.c.) or by surgical pulmonary artery banding. PDE5 inhibition using oral sildenafil (50 mg/kg/day in drinking water) or placebo was initiated 14 days after monocrotaline treatment and continued for 14 days until final examination. In the pulmonary artery banding groups, rats were treated with sildenafil (50 mg/kg/day) or placebo for 21 days following surgical pulmonary artery banding. At the final experiments, right-ventricular haemodynamics were measured and remodelling was analysed using histological, biochemical, and gene expression markers. Both monocrotaline and pulmonary artery banding increased right-ventricular systolic pressure to approximately 80 mmHg. In parallel, both interventions induced markers of hypertrophy (upregulation of natriuretic peptides, increase in myocyte diameter) and fibrosis (upregulation of collagen types 1A2 and 3A1) as well as mRNA expression of the tissue inhibitor of matrix metalloproteases 1 and osteopontin in the right ventricle. In monocrotaline model, sildenafil decreased pulmonary pressure, reduced right-ventricular hypertrophy, and prevented fibrosis marker gene upregulation. After pulmonary artery banding, in contrast, sildenafil increased markers of myocardial remodelling and right-ventricular myocyte diameter. CONCLUSION: Sildenafil prevents myocardial remodelling in pulmonary hypertension through an indirect action via right-ventricular unloading.

Combined tyrosine and serine/threonine kinase inhibition by sorafenib prevents progression of experimental pulmonary hypertension and myocardial remodeling.

BACKGROUND: Inhibition of tyrosine kinases, including platelet-derived growth factor receptor, can reduce pulmonary arterial pressure in experimental and clinical pulmonary hypertension. We hypothesized that inhibition of the serine/threonine kinases Raf-1 (also termed c-Raf) and b-Raf in addition to inhibition of tyrosine kinases effectively controls pulmonary vascular and right heart remodeling in pulmonary hypertension. METHODS AND RESULTS: We investigated the effects of the novel multikinase inhibitor sorafenib, which inhibits tyrosine kinases as well as serine/threonine kinases, in comparison to imatinib, a tyrosine kinase inhibitor, on hemodynamics, pulmonary and right ventricular (RV) remodeling, and downstream signaling in experimental pulmonary hypertension. Fourteen days after monocrotaline injection, male rats were treated orally for another 14 days with sorafenib (10 mg/kg per day), imatinib (50 mg/kg per day), or vehicle (n=12 to 16 per group). RV systolic pressure was decreased to 35.0+/-1.5 mm Hg by sorafenib and to 54.0+/-4.4 mm Hg by imatinib compared with placebo (82.9+/-6.0 mm Hg). In parallel, both sorafenib and imatinib reduced RV hypertrophy and pulmonary arterial muscularization. The effects of sorafenib on RV systolic pressure and RV mass were significantly greater than those of imatinib. Sorafenib prevented phosphorylation of Raf-1 and suppressed activation of the downstream ERK1/2 signaling pathway in RV myocardium and the lungs. In addition, sorafenib but not imatinib antagonized vasopressin-induced hypertrophy of the cardiomyoblast cell line H9c2. CONCLUSIONS: The multikinase inhibitor sorafenib prevents pulmonary remodeling and improves cardiac and pulmonary function in experimental pulmonary hypertension. Sorafenib exerts direct myocardial antihypertrophic effects, which appear to be mediated via inhibition of the Raf kinase pathway. The combined inhibition of tyrosine and serine/threonine kinases may provide an option to treat pulmonary arterial hypertension and associated right heart remodeling.

Perceptual distortions produce multidimensional stress profiles in novice users of an endoscopic surgery simulator.

OBJECTIVES: We determine the impact of perceptual-motor distortions on multidimensional stress dynamics in novice users of an endoscopic/laparoscopic surgery simulator during performance of a peg-transfer task. BACKGROUND: Surgeons find the endoscopic/laparoscopic surgery procedure to be more mentally stressful than open surgery. This investigation was designed to identify specific stress dimensions associated with these procedures and to determine the contributions to that stress made by loss of depth information resulting from image-guided views of the surgical field and by disruption of eye-hand mapping. Because stress reactions might depend upon familiarity with these procedures, the study focused upon novice participants. METHOD: An endoscopic box-simulator featured in surgical training was used in conjunction with the Dundee Stress State Questionnaire, a well-validated multidimensional stress state instrument. A control group (no perceptual distortions) viewed the simulated "surgical field" directly. Two other groups viewed the surgical field through TV images in which spatial rotation of the images was absent or in which the images were rotated 90 degrees from the actual line of sight. RESULTS: Performance efficiency in the simulator varied inversely with the degree of perceptual-motor distortion. Reactions reflecting increased task coping were observed in all groups. These were accompanied in the image groups by negative reactions involving decreases in hedonic tone and control and confidence and an increase in tense arousal. CONCLUSIONS: Perceptual-motor distortions are sources of complex task-induced stress profiles in novices using an endoscopic surgery simulator. APPLICATION: Procedures to reduce stress in endoscopic/laparoscopic surgery trainees may benefit from knowledge regarding specific stress dimensions involved.

Plasma biomarkers of myocardial fibrosis and remodeling in terminal heart failure patients supported by mechanical circulatory support devices.

BACKGROUND: In this study we analyzed putative biomarkers for myocardial remodeling in plasma from 55 endstage heart failure patients with the need for mechanical circulatory support (MCS). We compared our data to 40 healthy controls and examined if MCS by either ventricular assist devices or total artificial hearts has an impact on plasma concentrations of remodeling biomarkers. METHODS & RESULTS: Plasma biomarkers were analysed pre and 30 days post implantation of a MCS device using commercially available enzyme linked immunosorbent assays (ELISA). We observed that the plasma concentrations of remodeling biomarkers: tissue inhibitor of metalloproteinase 1 (TIMP1), tenascin C (TNC), galectin 3 (LGALS3), osteopontin (OPN) and of neurohumoral biomarker brain natriuretic peptide (BNP), are significantly elevated in patients with terminal heart failure compared to healthy controls. We did not find elevated plasma concentrations for matrix metalloproteinase 2 (MMP2) and procollagen I C-terminal peptide (PCIP). However, only BNP plasma levels were reduced by MCS, whereas the concentrations of remodeling biomarkers remained elevated or even increased further 30 days after MCS. LGALS3 plasma concentrations at device implantation were significantly higher in patients who did not survive MCS due to multi organ failure (MOF). CONCLUSIONS: Our findings indicate that mechanical unloading in endstage heart failure is not reflected by a rapid reduction of remodeling plasma biomarkers.

Plasma concentrations of matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-1 and osteopontin reflect severity of heart failure in DOCA-salt hypertensive rat.

The matrix metalloproteinases (MMPs) and their endogenous inhibitors, the tissue inhibitors of metalloproteinases (TIMPs) play a key role in extracellular matrix maintenance and are altered in the failing heart, both in experimental models and in chronic end-stage heart failure in humans. As the common diagnostic markers of heart failure, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) primarily reflect increased pressure loading, determination of soluble, heart-derived MMPs and TIMPs in plasma, as well as the determination of the emerging fibrosis marker osteopontin (OPN) might be valuable tools for detecting heart fibrosis. In this study the effect of spironolactone treatment on plasma MMP-2, TIMP-1 and OPN levels was assessed in a heart failure animal model. Unilaterally nephrectomized Sprague Dawley rats received subcutaneous injection of 100 mg deoxycorticosterone acetate (DOCA) once a week and 1% (w/v) NaCl in drinking water. Blood pressure was monitored weekly and blood samples were collected after 1, 2 and 4 weeks. After 6 weeks, left ventricular contractility (LVC) and heart weight-to-body weight ratio (HW/BW) were assessed. DOCA treatment increased plasma MMP-2, TIMP-1 and OPN concentrations. Alterations of plasma marker levels were correlated with changes of HW/BW and paralleled impaired LVC. Furthermore, beneficial effects of spironolactone treatment were observed. In DOCA-salt hypertensive rats, plasma concentrations of MMP-2, TIMP-1 and OPN reflected heart failure associated with haemodynamic, functional and morphological changes. Based on these findings, it appears reasonable to use plasma markers of fibrosis to monitor the development of heart failure.

Differential brain activation according to chronic social reward frustration.

Neural correlates of reward frustration are increasingly studied in humans. In line with prediction error theory, omission of an expected reward is associated with relative decreases of cerebral activation in dopaminergic brain areas. We investigated whether a history of chronic work-related reward frustration influences this reward-dependent activation pattern by means of functional magnetic resonance imaging. Solving arithmetic tasks was followed by either monetary reward or omission of reward. Hyperactivations in the medial prefrontal, anterior cingulate and dorsolateral prefrontal cortex were observed in a group of healthy adults with high susceptibility to reward frustration as compared with a group with low susceptibility. Findings indicate a compromised ability of adapting brain activation among those suffering form chronic social reward frustration.

Same or different? Neural correlates of happy and sad mood in healthy males.

Emotional experience in healthy men has been shown to rely on a brain network including subcortical as well as cortical areas in a complex interaction, which may be substantially influenced by many internal personal and external factors such as individuality, gender, stimulus material and task instructions. The divergent results may be interpreted by taking these considerations into account. Hence, many aspects remain to be clarified in characterizing the neural correlates underlying the subjective experience of emotion. One unresolved question refers to the influence of emotion quality on the cerebral substrates. Hence, 26 male healthy subjects were investigated with functional magnetic resonance imaging during standardized sad and happy mood induction as well as a cognitive control task to explore brain responses differentially involved in positive and negative emotional experience. Sad and happy mood in contrast to the control task produced similarly significant activations in the amygdala-hippocampal area extending into the parahippocampal gyrus as well as in the prefrontal and temporal cortex, the anterior cingulate, and the precuneus. Significant valence differences emerged when comparing both tasks directly. More activation has been demonstrated in the ventrolateral prefrontal cortex (VLPFC), the anterior cingulate cortex (ACC), the transverse temporal gyrus, and the superior temporal gyrus during sadness. Happiness, on the other hand, produced stronger activations in the dorsolateral prefrontal cortex (DLPFC), the cingulate gyrus, the inferior temporal gyrus, and the cerebellum. Hence, negative and positive moods reveal distinct cortical activation foci within a common neural network, probably making the difference between qualitatively different emotional feelings.