Patients cured by cisplatin-based chemotherapy for metastatic testicular cancer have to be cognizant of their unfavorable cardiovascular risk profile, that might be a greater risk than developing a relapse or second malignancy.

Understanding the function of a protein requires not only knowledge of its tertiary structure but also an understanding of its conformational dynamics. Nuclear magnetic resonance (NMR) spectroscopy, polarization-resolved fluorescence spectroscopy and molecular dynamics (MD) simulations are powerful methods to provide detailed insight into protein dynamics on multiple time scales by monitoring global rotational diffusion and local flexibility (order parameters) that are sensitive to inter-and intramolecular interactions, respectively. We present an integrated approach where data from these techniques are analyzed and interpreted within a joint theoretical description of depolarization and diffusion, demonstrating their conceptual similarities. This integrated approach is then applied to the autophagy-related protein GABARAP in its cytosolic form, elucidating its dynamics on the pico-to nanosecond time scale and its rotational and translational diffusion for protein concentrations spanning 9 orders of magnitude. We compare the dynamics of GABARAP as monitored by 15 N spin relaxation of the backbone amide groups, fluorescence anisotropy decays and fluorescence correlation spectroscopy of side chains labeled with BODIPY FL, and molecular movies of the protein from MD simulations. The recovered parameters agree very well between the distinct techniques if the different measurement conditions (probe localization, sample concentration) are taken into account. Moreover, we propose a method that compares the order parameters of the backbone and side chains to identify potential hinges for large-scale, functionally relevant intradomain motions, such as residues 27/28 at the interface between the two subdomains of GABARAP. In conclusion, the integrated concept of cross-fertilizing techniques presented here is fundamental to obtaining a comprehensive quantitative picture of multiscale protein dynamics and solvation. The possibility to employ these validated techniques under cellular conditions and combine them with fluorescence imaging opens up the perspective of studying the functional dynamics of GABARAP or other proteins in live cells.

Purpose The aim of this study was to estimate the prevalence of pain, the extent of analgesics intake and the mental health status of German pre-hospital emergency medical service (EMS) personnel. Methods We conducted a nationwide online survey, which consisted of sociodemographic and job-related items, questions on pain and analgesics intake and the short-version of the validated Depression–Anxiety–Stress Scale (DASS-21). Results A total of 774 EMS personnel with a mean age of 33.03 (standard error [SE] 0.37) years were included into the final analysis of which 23.77% were female. Pain was reported by 58.64% (454 of 774) of the study participants with 10.72% (95% confidence interval [CI] 8.54%; 13.29%) suffering from chronic, 1.68% (95% CI 0.89%; 2.87%) from acute and 46.25% (95% CI 41.49%; 51.30%) from recurrent pain, respectively. Most frequent location of pain was lumbar spine. Analgesics were used by 52.76% (239 of 454) of pre-hospital EMS personnel with pain (acute 76.92% / chronic 69.88% / recurrent 47.90%). Moreover, participants with chronic and recurrent pain indicated significantly higher depression (p ≤ 0.001), anxiety (p ≤ 0.001), and stress (p ≤ 0.001) levels compared to those without pain, respectively. Conclusion This study indicates a high prevalence of pain and analgesics usage in participating German pre-hospital EMS personnel and a poorer mental health in those with chronic and recurrent pain. Therefore, disease prevention and health promotion measures are needed to preserve health of pre-hospital EMS personnel.