The role of research competence as an influencing factor for the careers of young academics. Findings and implications from studies on doctorates in medicine and life sciences in Germany.

Background: When viewed internationally, Germany boasts a high rate of doctoral candidates. Fields such as medicine and life sciences have a notably high proportion of doctoral students, a trend rooted in historical factors. Despite this, comprehensive empirical studies concerning the doctoral phase and early-career researchers, especially in relation to the rise of structured doctoral programmes, have only recently gained traction. Methods: We present findings from a project investigating young scientists in medicine and life sciences. Postdoctoral graduates from these disciplines were examined both quantitatively and qualitatively within the E-Prom projects, emphasizing the primary domain of research. Results: Our analysis indicates some benefits of structured doctoral programmes over traditional individual doctorates. However, the disparities between these doctoral approaches are less pronounced than anticipated. We also identified discrepancies between the programme descriptions and their actual execution. Integration into the scientific community and research-related self-efficacy are potential indicators of publication output and inclination towards a scientific career. Physicians exhibited lower research-related self-efficacy and a lesser tendency towards a scientific career than biologists. Notably, we found gender disparities disadvantaging female graduates, with these disparities being more marked in medicine. Conclusions: There is evidence to suggest that official representations of structured doctoral programmes do not always align with their practical applications, limiting their potential effectiveness. Therefore, resources should be allocated to ensure the consistent execution of these programmes. Given the empirical evidence supporting the benefits of community integration for junior researchers, efforts should be made to facilitate their networking. Additionally, our findings emphasize the necessity of providing enhanced support for young female scientists.

Development of Photoswitchable Tethered Ligands that Target the µ-Opioid Receptor.

Converting known ligands into photoswitchable derivatives offers the opportunity to modulate compound structure with light and hence, biological activity. In doing so, these probes provide unique control when evaluating G-protein-coupled receptor (GPCR) mechanism and function. Further conversion of such compounds into covalent probes, known as photoswitchable tethered ligands (PTLs), offers additional advantages. These include localization of the PTLs to the receptor binding pocket. Covalent localization increases local ligand concentration, improves site selectivity and may improve the biological differences between the respective isomers. This work describes chemical, photophysical and biochemical characterizations of a variety of PTLs designed to target the µ-opioid receptor (µOR). These PTLs were modeled on fentanyl, with the lead disulfide-containing agonist found to covalently interact with a cysteine-enriched mutant of this medically-relevant receptor.

Photochromic Fentanyl Derivatives for Controlled µ-Opioid Receptor Activation.

Photoswitchable ligands as biological tools provide an opportunity to explore the kinetics and dynamics of the clinically relevant µ-opioid receptor. These ligands can potentially activate or deactivate the receptor when desired by using light. Spatial and temporal control of biological activity allows for application in a diverse range of biological investigations. Photoswitchable ligands have been developed in this work, modelled on the known agonist fentanyl, with the aim of expanding the current "toolbox" of fentanyl photoswitchable ligands. In doing so, ligands have been developed that change geometry (isomerize) upon exposure to light, with varying photophysical and biochemical properties. This variation in properties could be valuable in further studying the functional significance of the µ-opioid receptor.

Prevalence of sport injuries in Olympic combat sports: a cross-sectional study examining one Olympic period.

BACKGROUND: Due to full contact impacts in combat sports, the risk of injuries is elevated. The aim of this study is to report severe injuries among athletes in Olympic combat sports. Specific injury types, time loss, and the performance level after injury are examined. METHODS: Survey to investigate injuries in Olympic combat sports during the time period from 2012-2016. Reported injuries were analyzed by anatomical location, injury type, gender, time loss, and performance level. RESULTS: The three injuries resulting in the longest time loss (ACL rupture: judo= 37 weeks; karate = 49 weeks; shoulder dislocation: wrestling = 41 weeks; shoulder rotator cuff injury: wrestling = 32 weeks) also accounted for the largest proportion of athletes with career-ending injuries (ACL rupture: judo = 28%; karate = 67%; shoulder dislocation: wrestling = 40%; shoulder rotator cuff injury: wrestling = 50%). Taekwondo and fencing had the shortest time loss (<12 weeks) among all combat sports. More injuries occurred during training (58%) as compared to competition (42%). Injury prevalence of competitive athletes was significantly higher as compared to recreational athletes. Male athletes suffered significantly more anterior cruciate ligament injuries (72% vs. 56%; P<0.05), unspecific shoulder injuries (89% vs. 47%; P<0.01), and elbow ligament injuries (57% vs. 30%; P<0.05) during training. CONCLUSIONS: The study shows that there are important differences between "punching and kicking" and "throwing" martial arts in terms of specific injury types. In judo and wrestling, the injuries are more likely to affect the joints (knee and shoulder). Therefore, injury prevention these sports should focus on strength training of the muscles surrounding the joints and on defensive reactionary movements to avoid dangerous biomechanical joint angles. In "punching and kicking" sports, injuries of the hands and feet, due to the large impact forces of strikes and kicks, could be reduced by improved protective equipment on hands and feet.

Epidemiology of injuries in track and field athletes: a cross-sectional study of specific injuries based on time loss and reduction in sporting level.

OBJECTIVES: To prevent the occurrence of injury in a sport, exact knowledge of injury patterns is needed. To synthesize sport-specific injuries in track and field comparing elite and recreational level athletes, as well as gender. Furthermore, analyze the time loss due to injury and reduction in athletic performance. METHODS: Injury type-specific frequencies were recorded according to discipline, gender and performance level. Injury severity was assessed by time loss duration and performance reduction. RESULTS: 64% of athletes suffered at least one injury. In the top 10 ranking, 83% (n = 524) were located in the lower extremities. A muscle strain of the thigh had the highest prevalence in sprint (34%, n = 41), jump (15%, n = 15) and middle-distance running (16%, n = 6). More injuries occurred during training (75%, n = 165) as compared to competition (25%, n = 56). The longest time loss was documented in throwing with a downtime of 36 weeks after a ligament injury of the elbow and 39 weeks after a muscle injury of the elbow. The injury with the highest number of athletes with a reduced level of performance was the foot ligament injury in sprint athletes at 100%. CONCLUSION: Assessing time loss and performance reduction in athletics, there are discipline-specific injury patterns. This study points out the high prevalence of training injuries, highlighting the need for future investigations to adapt training management, improve medical care and rehabilitation with respect to every discipline.

Epidemiology of Injuries in Olympic Sports.

Injuries effect the performance of athletes. Severity of injuries is determined by time loss and sporting performance reduction. To treat injuries adequately, it is necessary to get an overview of varied injuries types in different sports disciplines. In a retrospective study 7.809 athletes from Germany, Switzerland and Austria competing in competitive or recreational levels of sports were included. Injury prevalence was highest in team sports (75%), followed by combat (64%), racquet (54%) and track and field (51%). Knee (28%) and shoulder (14%) were the most at risk joints. Time loss in sporting activity after injury was longest in the region of knee (26 weeks). Of all reported injuries, 48% were accompanied by a reduced level of performance. The highest injury prevalence occurred in the year 2016 (45%). More injuries occurred during training (58%) compared to competition (42%). Across Olympic disciplines, a large number of injuries occurred during training sessions. Injury frequency increased as the Olympic games drew closer. Knee and shoulder injuries were the most severe injuries with respect to time loss and reduction sporting performance.

Regulations and practices of structured doctoral education in the life sciences in Germany.

Structured doctoral education is increasingly preferred compared to the individual model. Several science policy organisations give recommendations on how to structure doctoral education. However, there is little research on to what extent these recommendations find their way into practice. In our study, we first compared European and German recommendations on doctoral education with, second, the institutional regulations of structured doctoral programmes (N = 98) in the life sciences at twelve different German universities. Additionally, we third asked doctoral graduates (N = 1796) of these structured doctoral programmes and graduates of individual doctoral studies about their experience in doctoral education. Fourth, we contrasted the regulations of structured doctoral programmes with the reported experiences of their graduates. We found significant deviations of the reported practices of graduates from the regulations of their organisations, regarding the student admission, supervision and curricular activities of doctoral candidates. The efficacy of structured versus traditional doctoral education should be examined based on reported practice rather than on the respective written regulations.

Side Differences Regarding the Limb Symmetry Index in Healthy Professional Athletes.

Side differences in the limb symmetry index during hop tests have been rarely investigated in uninjured athletes. Unknown differences can result in false interpretation of hop tests and affect return to sport decision. Hypothesis was that un-injured athletes in Judo and Taekwondo have side differences in hop test and that asymmetries can be predicted based on the athletes fighting display. Differences, risk relationships were analyzed using the chi-squared test and the odds ratio. A two-tailed p value of<0.05 was considered statistically significant. 115 athletes from the national teams were included (mean age 18.4 years; range 13-27 years). 93, 97.4 and 98.3% did not have symmetric hop distance for three hop tests. Up to a quarter did not reach a limb symmetry index of>90. Moreover, 57.4% (n=66) reached longer jumping distance with the standing leg. Ignoring such pre-existent side differences in evaluation of hop tests and not knowing which limb was dominant prior the injury, can lead to premature or delayed return to sports in the rehabilitation process. Therefore, it might be helpful to refer to individual jump lengths for each limb in case of injury by using hop tests in pre-season screening in professional athletes in Judo and Taekwondo.

Photochromic Dopamine Receptor Ligands Based on Dithienylethenes and Fulgides.

We describe the incorporation of the well-investigated class of photochromic dithienylethenes (DTEs) and fulgides into known dopamine receptor ligands such as 1,4-disubstituted aromatic and hydroxybenzoxazinone piperazines as well as aminoindanes. Subtype and functional selective photochromic ligands were obtained and characterized by NMR and UV/VIS spectroscopic measurements. The photophysical properties of the DTE based dopamine ligands revealed a high fatigue resistance for the diarylmaleimides, but the ringclosure could not be accomplished in polar solvents due to a known twisted intramolecular charge transfer (TICT). Several cyclopentene-DTEs showed high PSS, but a fast degradation by forming an irreversible byproduct. Focusing on the fulgides, high photostationary states and switching in polar solvents were possible. The compounds 43, 45 and 46 containing the isopropyl group showed only isomerization between the open E-form and the closed C-form. At a concentration of 1 nm, the cyclopentene-DTE 29-open showed a more than 11-fold higher activation of D2S , a pharmacologically important G protein-coupled receptor, than its photochromic congener 29-closed. Interestingly, the fulgimide-based pair 52-(E)-open/52-closed could be discovered as an alternative photoswitch with inverse activation properties exhibiting four-fold higher activity in the closed state.

NTS2-selective neurotensin mimetics with tetrahydrofuran amino acids.

Stimulation of the NTS2 neurotensin receptor causes antipsychotic effects and leads to a promotion of the µ-opioid-independent antinociception, which is important in the modulation of tonic pain sensitivity. We report the synthesis and properties of a small library of peptidic agonists based on the active neurotensin fragment NT(8-13). Two tetrahydrofuran amino acid derivatives were synthesized to replace Tyr11 in NT(8-13). Additionally, Arg8, Arg9, and Ile12 of the lead peptide were exchanged by Lys, Lys, and Gly, respectively. The new compounds showed substantial NTS2 binding affinity and up to 1000-fold selectivity over NTS1. The highest selectivity (Ki(NTS2): 29nM, Ki(NTS1): 35,000nM) was observed for the peptide analog 17Rtrans.

Synthetic incorporation of Nile Blue into DNA using 2'-deoxyriboside substitutes: Representative comparison of (R)- and (S)-aminopropanediol as an acyclic linker.

The Nile Blue chromophore was incorporated into oligonucleotides using "click" chemistry for the postsynthetic modification of oligonucleotides. These were synthesized using DNA building block 3 bearing an alkyne group and reacted with the azide 4. (R)-3-amino-1,2-propanediol was applied as the linker between the phosphodiester bridges. Two sets of DNA duplexes were prepared. One set carried the chromophore in an A-T environment, the second set in a G-C environment. Both were characterized by optical spectroscopy. Sequence-dependent fluorescence quenching was applied as a sensitive tool to compare the stacking interactions with respect to the chirality of the acyclic linker attachment. The results were compared to recent results from duplexes that carried the Nile Blue label in a sequentially and structurally identical context, except for the opposite chirality of the linker ((S)-3-amino-1,2-propandiol). Only minor, negligible differences were observed. Melting temperatures, UV-vis absorption spectra together with fluorescence quenching data indicate that Nile Blue stacks perfectly between the adjacent base pairs regardless of whether it has been attached via an S- or R-configured linker. This result was supported by geometrically optimized DNA models.

Comparison of a nucleosidic vs non-nucleosidic postsynthetic "click" modification of DNA with base-labile fluorescent probes.

The azides 1 and 2 bearing a phenoxazinium and a coumarin fluorophore, respectively, were applied in postsynthetic "click"-type bioconjugation and coupled to oligonucleotides modified with alkyne groups using two alternative approaches: (i) as a nucleotide modification at the 2'-position of uridine and (ii) as a nucleotide substitution using (S)-(-)-3-amino-1,2-propanediol as an acyclic linker between the phosphodiester bridges. The corresponding alkynylated phosporamidites 3 and 6 were used as DNA building blocks for the preparation of alkyne-bearing DNA duplexes. The base pairs adjacent to the site of modification and the base opposite to it were varied in the DNA sequences. The modified duplexes were investigated by UV/vis absorption spectroscopy (including melting temperatures) and fluorescence spectroscopy in order to study the different optical properties of the two chromophores and to evaluate their potential for bioanalytical applications. The sequence-selective fluorescence quenching of phenoxazinium 1 differs only slightly and does not depend on the type of modification, meaning whether it has been attached to the 2'-position of uridine or as DNA base surrogate using the acyclic glycol linker. The 2'-chromophore-modified uridine still recognizes adenine as the counterbase, and the duplexes exhibit a sufficient thermal stability that is comparable to that of unmodified duplexes. Thus, the application of the 2'-modification site of uridine is preferred in comparison to glycol-assisted DNA base surrogates. Accordingly, the coumarin dye azide 2 was attached only to the 2'-position of uridine. The significant Stokes shift of approximately 100 nm and the good quantum yields make the coumarin chromophore a powerful fluorescent label for nucleic acids.