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We used single-molecule FRET in combination with other biophysical methods and molecular simulations to investigate the effect of temperature on the dimensions of unfolded proteins. With singlemolecule FRET, this question can be addressed even under nearnative conditions, where most molecules are folded, allowing us to probe a wide range of denaturant concentrations and temperatures. We find a compaction of the unfolded state of a small cold shock protein with increasing temperature in both the presence and the absence of denaturant, with good agreement between the results from single-molecule FRET and dynamic light scattering. Although dissociation of denaturant from the polypeptide chain with increasing temperature accounts for part of the compaction, the results indicate an important role for additional temperaturedependent interactions within the unfolded chain. The observation of a collapse of a similar extent in the extremely hydrophilic, intrinsically disordered protein prothymosin suggests that the hydrophobic effect is not the sole source of the underlying interactions. Circular dichroism spectroscopy and replica exchange molecular dynamics simulations in explicit water show changes in secondary structure content with increasing temperature and suggest a contribution of intramolecular hydrogen bonding to unfolded state collapse.
Introduction: Cardiac rehabilitation is designed for patients suffering from cardiovascular diseases or functional disabilities. The aim of a cardiac rehabilitation is to improve overall physical health, psychological well-being, physical function, the ability to participate in social life and help patients to change their habits. Regarding the heterogeneity of these aims measuring of the effect of cardiac rehabilitation is still a challenge. This study recommends a concept to assess the effects of cardiac rehabilitation regarding the individual change of relevant quality indicators.
Methods: With EVA-Reha; cardiac rehabilitation the Medical Advisory Service of Statutory Health Insurance Funds in Rhineland-Palatinate, Alzey (MDK Rheinland-Pfalz) developed a software to collect data set including sociodemographic and diagnostic data and also the results of specific assessments. The project was funded by the Techniker Krankenkasse, Hamburg, and supported by participating rehabilitation centers. From 01. July 2010 to 30. June 2011 1309 patients (age 71.5 years, 76.1% men) from 13 rehabilitation centers were consecutively enrolled. 13 quality indicators in 3 scales were developed for evaluation of cardiac rehabilitation: 1) cardiovascular risk factors (blood pressure, LDL cholesterol, triglycerides), 2) exercise capacity (resting heart rate, maximal exercise capacity, maximal walking distance, heart failure [NYHA classification], and angina pectoris [CCS classification]) and 3) subjective health (IRES-24: pain, somatic health, psychological wellbeing and depression as well as anxiety on the HADS). The study was prospective; data of patients were assessed at entry and discharge of rehabilitation. To measure the success of rehabilitation each parameter was graded in severity classes at entry and discharge. For each of the 13 quality indicators changes of severity class were rated in a rating matrix. For indicators without a requirement for medical care neither at entry nor at discharge no rating was performed.
Results: The grading into severity classes as well as the minimal important differences were given for the 13 quality indicators. The result of rehabilitation can be demonstrated in suitable form by means of rating of the 13 quality indicators according to a clinical population. The rating model differs well between clinically changed and unchanged patients for the quality indicators.
Conclusion: The result of cardiac rehabilitation can be assessed with 13 quality indicators measured at entry and discharge of the rehabilitation program. If a change into a more favorable category at the end of rehabilitation could be achieved it was counted as a success. The 13 quality indicators can be used to assess the individual result as well as the result of a population - e.g. all patients of a clinic in a specific time period. In addition, the assessment and rating of relevant quality indicators can be used for comparisons of rehabilitation centers.
The Richardson-Lucy deconvolution algorithm was applied to astronomical images in the very high-energy regime with photon energies above 100 GeV. Through a systematic study with respect to source significance, background level and source morphology we were able to derive optimal deconvolution parameters. The results presented show that deconvolution makes it possible to study structural details well below the angular resolution of the very high-energy gamma-ray experiment. (C) 2012 Elsevier B.V. All rights reserved.
Background Exercise rehabilitation is highly recommended by current guidelines on prevention of cardiovascular disease, but its implementation is still poor. Many clinicians experience difficulties in prescribing exercise in the presence of different concomitant cardiovascular diseases and risk factors within the same patient. It was aimed to develop a digital training and decision support system for exercise prescription in cardiovascular disease patients in clinical practice: the European Association of Preventive Cardiology Exercise Prescription in Everyday Practice and Rehabilitative Training (EXPERT) tool. Methods EXPERT working group members were requested to define (a) diagnostic criteria for specific cardiovascular diseases, cardiovascular disease risk factors, and other chronic non-cardiovascular conditions, (b) primary goals of exercise intervention, (c) disease-specific prescription of exercise training (intensity, frequency, volume, type, session and programme duration), and (d) exercise training safety advices. The impact of exercise tolerance, common cardiovascular medications and adverse events during exercise testing were further taken into account for optimized exercise prescription. Results Exercise training recommendations and safety advices were formulated for 10 cardiovascular diseases, five cardiovascular disease risk factors (type 1 and 2 diabetes, obesity, hypertension, hypercholesterolaemia), and three common chronic non-cardiovascular conditions (lung and renal failure and sarcopaenia), but also accounted for baseline exercise tolerance, common cardiovascular medications and occurrence of adverse events during exercise testing. An algorithm, supported by an interactive tool, was constructed based on these data. This training and decision support system automatically provides an exercise prescription according to the variables provided. Conclusion This digital training and decision support system may contribute in overcoming barriers in exercise implementation in common cardiovascular diseases.
Since the beginning of the 1970s a lot of countries in Latin America has been starting the transition to democracy. The article analyses the role played by the military in this process, especially the effects of civildemocratic governments – sometimes failing in – gaining power over the military. It is described how and why the army occasionally kept their independence from the civil power and how this influenced the consolidation of democracy.
Background: Pavlovian processes are thought to play an important role in the development, maintenance and relapse of alcohol dependence, possibly by influencing and usurping on- going thought and behavior. The influence of Pavlovian stimuli on on-going behavior is paradigmatically measured by Pavlovian-to-instrumental-transfer (PIT) tasks. These involve multiple stages and are complex. Whether increased PIT is involved in human alcohol
dependence is uncertain. We therefore aimed to establish and validate a modified PIT paradigm that would be robust, consistent, and tolerated by healthy controls as well as by patients suffering from alcohol dependence, and to explore whether alcohol dependence is associated with enhanced Pavlovian-Instrumental transfer.
Methods: 32 recently detoxified alcohol-dependent patients and 32 age and gender matched healthy controls performed a PIT task with instrumental go/no-go approach behaviours. The task involved both Pavlovian stimuli associated with monetary rewards and losses, and images of drinks.
Results: Both patients and healthy controls showed a robust and temporally stable PIT effect. Strengths of PIT effects to drug-related and monetary conditioned stimuli were highly correlated. Patients more frequently showed a PIT effect and the effect was stronger in response to aversively conditioned CSs (conditioned suppression), but there was no group difference in response to appetitive CSs.
Conclusion: The implementation of PIT has favorably robust properties in chronic alcohol- dependent patients and in healthy controls. It shows internal consistency between monetary and drug-related cues. The findings support an association of alcohol dependence with an increased propensity towards PIT.
BACKGROUND: Pavlovian-to-instrumental transfer (PIT) describes the influence of conditioned stimuli on instrumental behaviors and is discussed as a key process underlying substance abuse. Here, we tested whether neural responses during alcohol-related PIT predict future relapse in alcohol-dependent patients and future drinking behavior in adolescents. METHODS: Recently detoxified alcohol-dependent patients (n = 52) and young adults without dependence (n = 136) underwent functional magnetic resonance imaging during an alcohol-related PIT paradigm, and their drinking behavior was assessed in a 12-month follow-up. To predict future drinking behavior from PIT activation patterns, we used a multivoxel classification scheme based on linear support vector machines. RESULTS: When training and testing the classification scheme in patients, PIT activation patterns predicted future relapse with 71.2% accuracy. Feature selection revealed that classification was exclusively based on activation patterns in medial prefrontal cortex. To probe the generalizability of this functional magnetic resonance imaging-based prediction of future drinking behavior, we applied the support vector machine classifier that had been trained on patients to PIT functional magnetic resonance imaging data from adolescents. An analysis of cross-classification predictions revealed that those young social drinkers who were classified as abstainers showed a greater reduction in alcohol consumption at 12-month follow-up than those classified as relapsers (Delta = -24.4 +/- 6.0 g vs. -5.7 +/- 3.6 g; p = .019). CONCLUSIONS: These results suggest that neural responses during PIT could constitute a generalized prognostic marker for future drinking behavior in established alcohol use disorder and in at-risk states.
Rationale: Advances in neurocomputational modeling suggest that valuation systems for goal-directed (deliberative) on one side, and habitual (automatic) decision-making on the other side may rely on distinct computational strategies for reinforcement learning, namely model-free vs. model-based learning. As a key theoretical difference, the model-based system strongly demands cognitive functions to plan actions prospectively based on an internal cognitive model of the environment, whereas valuation in the model-free system relies on rather simple learning rules from operant conditioning to retrospectively associate actions with their outcomes and is thus cognitively less demanding. Acute stress reactivity is known to impair model-based but not model-free choice behavior, with higher working memory capacity protecting the model-based system from acute stress. However, it is not clear which impact accumulated real life stress has on model-free and model-based decision systems and how this influence interacts with cognitive abilities. Methods: We used a sequential decision-making task distinguishing relative contributions of both learning strategies to choice behavior, the Social Readjustment Rating Scale questionnaire to assess accumulated real life stress, and the Digit Symbol Substitution Test to test cognitive speed in 95 healthy subjects. Results: Individuals reporting high stress exposure who had low cognitive speed showed reduced model-based but increased model-free behavioral control. In contrast, subjects exposed to accumulated real life stress with high cognitive speed displayed increased model-based performance but reduced model-free control. Conclusion: These findings suggest that accumulated real life stress exposure can enhance reliance on cognitive speed for model-based computations, which may ultimately protect the model-based system from the detrimental influences of accumulated real life stress. The combination of accumulated real life stress exposure and slower information processing capacities, however, might favor model-free strategies. Thus, the valence and preference of either system strongly depends on stressful experiences and individual cognitive capacities.