Open Access

The hairpin ribozyme is a small Mg2+-dependent catalytic RNA molecule able to catalyze the trans-cleavage of an RNA substrate via a reversible trans-esterification mechanism. In this study, the cleavage activities of several fragmented hairpin ribozyme systems were examined. Due to the complex catalytic structure of the hairpin ribozyme, a new boronic acid ester was used as a covalent linkage to hold the folding of the functional system. It has been demonstrated the possibility of replacing the phosphodiester linkage, at specific positions, with a boronic acid ester to restore or improve the catalytic activity of fragmented hairpin ribozyme.

Zusammenfassung Die vorliegende Studie befasst sich mit der Morphologie des menschlichen Tuber maxillae unter Berücksichtigung alters- und geschlechtsspezifischer Unterschiede. Grundlage dieser Arbeit waren DVT-Datensätze von 118 erwachsenen Probanden beiderlei Geschlechts. Basierend auf den Rohdatensätzen wurden, mit Hilfe der NewTom 3G Software (QR NNT Version 2.11 Professional ©), Axialschnitte parallel zur Ebene des Nasenhöhlenbodens angefertigt. Die Schichtstärke der Axialschnitte betrug 3,0 mm. Die daraus resultierenden axialen DVT-Schichtaufnahmen waren die Basis für alle weiteren Untersuchungen. Im Folgenden konnte auf der Grundlage definierter Messpunkte und Hilfslinien, Streckenmessungen am Tuber maxillae vorgenommen werden. Diese Streckenmessungen waren Ausgangspunkt für die Definition unterschiedlicher Formentypen des Tuber maxillae. Um geschlechts- und altersspezifische Unterschiede zwischen den gewonnenen Messdaten und Formtypen des Tuber maxillae beurteilen zu können, wurde zunächst eine deskriptive Statistik erstellt. Darauf aufbauend erfolgte ein t-Test, durch den Geschlechtsunterschiede dargestellt werden konnten. Mit Hilfe einer einfaktoriellen Varianzanalyse (ANOVA) untersuchten wir die gewonnenen Daten in Bezug zu den drei Altersgruppen der erwachsenen Probanden. Des Weiteren nahmen wir eine Korrelations- und Regressionsanalyse unter Berücksichtigung verschiedener Gesichtsschädelmaße vor. Mit Hilfe der Bestimmung eines Symmetriequotienten erfolgte die Beurteilung von Seitenunterschieden. Anhand der Streckenmessungen des Tuber maxillae zeigte sich, dass der Tuber maxillae bei den Männern höher ist als bei den Frauen. Breite und Länge des Tuber maxillae sind jedoch geschlechtsunabhängig. Obgleich keine signifikanten Altersunterschiede in Bezug auf die Höhe des Tuber maxillae nachgewiesen werden konnten, wurden Unterschiede zwischen den Altersgruppen 2 und 3 beobachtet. So nahm die Höhe des Tuber maxillae bis zur Altersgruppe 2 zunächst zu, um bei den älteren Probanden in der Altersgruppe 3 wieder leicht abzunehmen. Das Symmetrieverhalten des Tuber maxillae zeigte im Bezug zur Höhe symmetrische Höhenmaße. Anders verhielt es sich bei der Breite und Länge des Tuber maxillae. Sowohl für die Breite als auch für die Länge zeigten sich bei über der Hälfte der Probanden Symmetrieunterschiede zwischen dem rechten und linken Tuber maxillae. Weiterhin konnte diese Studie verschiedene Korrelationen zwischen den Maßen des Tuber maxillae und verschiedenen Schädelmaßen aufzeigen. Eine weiterführende Regressionsanalyse bestätigte einen signifikanten Zusammenhang, insbesondere zwischen der Höhe des linken Tuber maxillae und dem Volumen des linken Sinus maxillaris. Basierend auf den in dieser Studie ermittelten Maßen des Tuber maxillae konnten dem Tuber maxillae sowohl in der Norma lateralis als auch in der Norma horizontalis drei verschiedene Formtypen zugeordnet werden. Für die Formbestimmung in der Norma lateralis wurden jeweils die größten Längen des Tuber maxillae von kranial nach kaudal auf Millimeterpapier übertragen und an der anterioren Begrenzung des Tuber maxillae ausgerichtet. Mit Hilfe der so gewonnen Skizzen definierten wir die Formtypen I, II und III. Beim Typ I beschreibt die Dorsalfläche des Tuber maxillae einen annährend geraden Verlauf von kranial nach kaudal. Der Typ II hingegen ist gekennzeichnet durch eine tendenzielle Zunahme der Dorsalfläche von kranial nach kaudal. Beim Typ III zeigt sich ein konkaver Verlauf der Dorsalfläche des Tuber maxillae. Unsere Untersuchungen zeigten, dass in der Norma lateralis der Typ III bei den Männern am häufigsten vorkam. Bei den weiblichen Probanden zeigte sich dagegen häufiger der Typ II. Die Formbestimmung des Tuber maxillae in der Norma horizontalis erfolgte an drei definierten Horizontalschnitten. Der erste Horizontalschnitt befindet sich auf Höhe des mittleren Nasenganges, der zweite Horizontalschnitt auf Höhe des Foramen palatinum majus und der dritte Horizontalschnitt in Höhe der Wurzelspitzen der Oberkiefermolaren. Die Einteilung in die Formen erfolgte in ähnlicher Weise wie in der Norma lateralis. Die größten Längen des Tuber maxillae wurden von lateral nach medial auf Millimeterpapier übertragen und wieder an der anterioren Begrenzung des Tuber maxillae ausgerichtet. Anhand der gewonnenen Skizzen definierten wir die Formtypen a, b und c für die Norma horizontalis. Beim Typ a befindet sich die stärkste Ausprägung der Dorsalfläche im medialen Drittel des Tuber maxillae. Der Typ b zeigt seine stärkste Ausprägung im mittleren Drittel des Tuber maxillae. Beim Typ c befindet sich die stärkste Ausprägung im lateralen Drittel des Tuber maxillae. Es zeigte sich, dass in Höhe des mittleren Nasenganges bei den Männern der Typ a am häufigsten auftrat. In Höhe des Foramen palatinum majus und auf Höhe der Wurzelspitzen der oberen Molaren ermittelten wir den Typ b am häufigsten. Bei den Frauen zeigte sich auf Höhe des mittleren Nasenganges der Typ a am häufigsten. Gleiches war auf Höhe des Foramen palatinum majus zu beobachten. In der Ebene der Wurzelspitzen der oberen Molaren zeigte sich häufiger der Typ b. Anhand der hier gewonnenen Daten ist es möglich, die Form des Tuber maxillae zu quantifizieren. Die Untersuchungsergebnisse können für verschiedene klinische Fachgebiete, wie die Mund-Kiefer-Gesichtschirurgie (MKG), die Prothetik und die Kieferorthopädie, von Interesse sein. In der MKG beispielweise können sie von Bedeutung bei der Wahl des passenden dentalen Implantatsystems in der Tuberregion sein. Aber auch bei der Gewinnung von Knochen aus der Tuberregion kann die Kenntnis über Form und Größe des Tuber maxillae von Nutzen sein. Die hier vorliegende Studie gibt Aufschluss über die Morphologie des Tuber maxillae beim Menschen. Weiterhin liefert sie Grundlagen für weiterführende Studien an anderen menschlichen Populationen.

Das Auftreten einer postoperativen Wundinfektion bedeutet für den Patienten die Verwirklichung eines gefürchteten persönlichen Risikos, stellt den behandelnden Ärzten oft vor schwer zu lösende Aufgaben und belastet die Solidargemeinschaft durch einen erheblichen Kostenanstieg. Obwohl Staphylococcus aureus weltweit als der häufigste und gefährlichste Erreger von SSI gilt, muss jede Klinik die lokalen Gegebenheiten (Erreger-Prävalenz, Resistenzlage etc.) kennen und sich ihnen stellen. Ziel der vorliegenden Arbeit war es, die Bedeutung von Staphyloccocus aureus für die Klinik und Poliklinik für Unfall-, Wiederherstellungschirurgie und Rehabilitative Medizin der Universitätsmedizin Greifswald zu untersuchen. Dazu wurden drei klinische Studien durchgeführt: zur Erfassung der Prävalenz von MRSA und MSSA, zur Untersuchung der Effektivität präoperativer Hautantiseptik bei unfallchirurgischen Patienten sowie zur Frage, ob Staphylococcus aureus als verursachendes Pathogen einer Implantat-assoziierten Infektion einen Risikofaktor für ein Wiederauftreten der Infektion nach erfolgter Therapie darstellt. Es konnte gezeigt werden, dass etwa ein Fünftel der Patienten der Unfallchirurgie Greifswald bereits bei Ankunft im Krankenhaus Träger von MRSA oder MSSA war. Während operativer Eingriffe gelang trotz einer leitliniengerecht durchgeführten Hautantisepsis nur bei 65% der Patienten eine vollständige Keimreduktion. In einem Fall konnte die Verschleppung eines MSSA-Klons von der präantiseptischen Hautflora in die postantiseptische Wundflora bewiesen werden. Nicht zuletzt hatten Patienten mit durch MSSA infiziertem Osteosynthesematerial ein deutlich erhöhtes Risiko einer Re-Infektion nach zunächst erfolgreicher Beruhigung der Infektion. Die Ergebnisse der drei durchgeführten Studien zeigen, dass Staphylococcus aureus auch in Greifswald bei der Behandlung unfallchirurgischer Patienten die antizipierte, bestimmende Rolle spielt. Prävalenz des Pathogen, Persistenz trotz etabliertem perioperativen Hygieneregime und Auswirkung einer tatsächlich eingetretenen Infektion auf die Heilungschancen wurden dargelegt. Den Fokus perioperativer Hygiene-Maßnahmen zur Vermeidung von SSI weiterhin auf Gram-positive Erreger, namentlich Staphylokokken, zu richten, ist aktuell in der Klinik für Unfallchirurgie in Greifswald gerechtfertigt.

Sturgeons are among the most ancient linages of actinopterygians. At present, many sturgeon species are critically endangered. Surrogate production could be used as an affordable and a time-efficient method for endangered sturgeons. Our study established a method for identifying and isolating type A spermatogonia from different developmental stages of testes using flow cytometric cell sorting (FCM). Flow cytometric analysis of a whole testicular cell suspension showed several well-distinguished cell populations formed according to different values of light scatter parameters. FCM of these different cell populations was performed directly on glass slides for further immunocytochemistry to identify germ cells. Results showed that the cell population in gate P1 on a flow cytometry plot (with high forward scatter and high side scatter parameter values) contains the highest amount of type A spermatogonia. The sorted cell populations were characterized by expression profiles of 10 germ cell specific genes. The result confirmed that setting up for the P1 gate could precisely sort type A spermatogonia in all tested testicular developmental stages. The P2 gate, which was with lower forward scatter and side scatter values mostly, contained type B spermatogonia at a later maturing stage. Moreover, expressions of plzf, dnd, boule, and kitr were significantly higher in type A spermatogonia than in later developed germ cells. In addition, plzf was firstly found as a reliable marker to identify type A spermatogonia, which filled the gap of identification of spermatogonial stem cells in sterlet. It is expected to increase the efficiency of germ stem cell culture and transplantation with plzf identification. Our study thus first addressed a phenotypic characterization of a pure type A spermatogonia population in sterlet. FCM strategy can improve the production of sturgeons with surrogate broodstock and further the analysis of the cellular and molecular mechanisms of sturgeon germ cell development.

Untersuchung des Einflusses der extrakorporalen Photopherese (ECP) auf die Lebensqualität (LQ) und den Krankheitsverlauf bei Patienten mit Mycosis Fungoides (MF) sowie mit Graft-versus-Host-Disease (GvHD).

Hintergrund Akupunktur wurde 2007 für die Indikationen chronische Knie- und Rückenschmerzen in den Leistungskatalog der gesetzlichen Krankenversicherung aufgenommen. Die Studie untersucht, wer Akupunktur erhält, wer Akupunktur anbietet und ob es zeitliche und regionale Unterschiede gibt. Methoden Für die retrospektive Beobachtungsstudie wurde eine knapp vier Millionen große Stichprobe anonymisierter GKV-Abrechnungsdaten verwendet. Diese ist für das Jahr 2013 gemäß Alter und Geschlecht repräsentativ für Deutschland. Ergebnisse Rückenschmerzen war die am häufigsten kodierte Indikation (86 %) für die Abrechnung von Akupunktur. Überwiegend Frauen nahmen Akupunktur in Anspruch, das mittlere Alter lag bei 61,1 Jahren. Bei 63 % der Versicherten mit Akupunktur in 2014 wurde jene erstmals abgerechnet, 37 % nahmen bereits in 2012 oder 2013 Akupunktur in Anspruch. Der Anteil an Versicherten mit frühzeitiger Beendigung (< 6 Sitzungen) ihres ersten Akupunkturbehandlungszyklus in 2014 betrug bei Knieschmerzpatienten 14 % und bei Rückenschmerzpatienten 21 %. Von 2008 bis 2015 ließ sich ein signifikant abnehmender Trend der Inanspruchnahme nachweisen. Es zeigten sich deutliche regionale Unterschiede zwischen den neuen und alten Bundesländern sowie den Stadtstaaten. Knapp 11 % aller durchführenden Ärzte rechneten die Hälfte aller erbrachten Sitzungen in 2014 ab. Diskussion Dass überwiegend Frauen im höheren Alter Akupunktur in Anspruch nehmen entspricht der Epidemiologie von Rücken- und Knieschmerzen sowie ihrer höheren Präferenz für komplementäre Behandlungsverfahren. Der hohe Anteil von Patienten, die Akupunktur wiederholt in Anspruch nehmen, deutet auf einen wahrgenommenen Nutzen in einer Teilgruppe hin. Dem gegenüber stehen die geringe und kontinuierlich abnehmende Inanspruchnahme sowie der hohe Anteil an frühzeitigen Beendigungen.

Students’ sense of belonging presents an essential resource for academic and health outcomes, whereas social exclusion at school negatively impacts students’ well‐being and academic performance. Aiming to understand how feelings of school‐related belonging and exclusion shape the structural brain development, this study applied longitudinal questionnaire‐based data and MRI data from 71 adolescent students (37 females, Mage at t1 = 15.0; t2 = 16.1 years). All were white participants from Germany. Voxel‐based morphometry revealed only an association of social exclusion (and not of belonging) and gray matter volume in the left anterior insula: From t1 to t2, there was less gray matter decrease, the more social exclusion students perceived. School‐related social exclusion and disturbed neurodevelopment are thus significantly associated.

Polyethylene terephthalate (PET) is a mass-produced petroleum-based non-biodegradable plastic that contributes to the global plastic pollution. Recently, biocatalytic degradation has emerged as a viable recycling approach for PET waste, especially with thermophilic polyester hydrolases such as a cutinase (LCC) isolated from a leaf-branch compost metagenome and its variants. To improve the enzymatic PET hydrolysis performance, we fused a chitin-binding domain (ChBD) from Chitinolyticbacter meiyuanensis SYBC-H1 to the C-terminus of the previously reported LCCICCG variant, demonstrating higher adsorption to PET substrates and, as a result, improved degradation performance by up to 19.6% compared to with its precursor enzyme without the binding module. For compare hydrolysis with different binding module, the catalytic activity of LCCICCG-ChBD, LCCICCG-CBM, LCCICCG-PBM and LCCICCG-HFB4 were further investigated with PET substrates of various crystallinity and it showed measurable activity on high crystalline PET with 40% crystallinity. These results indicated that fusing a polymer-binding module to LCCICCG is a promising method stimulating the enzymatic hydrolysis of PET.

The COVID-19 pandemic is one of the most serious health and economic crises of the 21st century. From a psychological point of view, the COVID-19 pandemic and its consequences can be conceptualized as a multidimensional and potentially toxic stressor for mental health in the general population. This selective literature review provides an overview of longitudinal studies published until June 2021 that have investigated the impact of the COVID-19 pandemic on mental health in the European population. Risk and protective factors identified in the studies are summarized. Forty-two studies that met inclusion and search criteria (COVID-19, mental health, longitudinal, and Europe) in PubMed, PsycInfo, and Web of Science databases indicate differential effects of the pandemic on mental distress, depression, and anxiety, depending on samples and methods used. Age-specific (e.g., young age), social (e.g., female, ethnical minority, loneliness), as well as physical and mental health-related factors (e.g., pre-pandemic illness) were identified as risk factors for poor mental health. The studies point to several protective factors such as social support, higher cognitive ability, resilience, and self-efficacy. Increasing evidence supports the assumption of the pandemic being a multidimensional stressor on mental health, with some populations appearing more vulnerable than others, although inconsistencies arise. Whether the pandemic will lead to an increase in the prevalence of mental disorders is an open question. Further high-quality longitudinal and multi-national studies and meta-analyses are needed to draw the complete picture of the consequences of the pandemic on mental health.

Factors causing the increased cardiovascular morbidity and mortality in hemodialysis (HD) patients are largely unknown. Oxylipins are a superclass of lipid mediators with potent bioactivities produced from oxygenation of polyunsaturated fatty acids. We previously assessed the impact of HD on oxylipins in arterial blood plasma and found that HD increases several oxylipins. To study the phenomenon further, we now evaluated the differences in arterial and venous blood oxylipins from patients undergoing HD. We collected arterial and venous blood samples in upper extremities from 12 end-stage renal disease (ESRD) patients before and after HD and measured oxylipins in plasma by LC-MS/MS tandem mass spectrometry. Comparison between cytochrome P450 (CYP), lipoxygenase (LOX), and LOX/CYP ω/(ω-1)-hydroxylase metabolites levels from arterial and venous blood showed no arteriovenous differences before HD but revealed arteriovenous differences in several CYP metabolites immediately after HD. These changes were explained by metabolites in the venous blood stream of the upper limb. Decreased soluble epoxide hydrolase (sEH) activity contributed to the release and accumulation of the CYP metabolites. However, HD did not affect arteriovenous differences of the majority of LOX and LOX/CYP ω/(ω-1)-hydroxylase metabolites. The HD treatment itself causes changes in CYP epoxy metabolites that could have deleterious effects in the circulation.

We are currently facing an antimicrobial resistance crisis, which means that a lot of bacterial pathogens have developed resistance to common antibiotics. Hence, novel and innovative solutions are urgently needed to combat resistant human pathogens. A new source of antimicrobial compounds could be bacterial volatiles. Volatiles are ubiquitous produced, chemically divers and playing essential roles in intra- and interspecies interactions like communication and antimicrobial defense. In the last years, an increasing number of studies showed bioactivities of bacterial volatiles, including antibacterial, antifungal and anti-oomycete activities, indicating bacterial volatiles as an exciting source for novel antimicrobial compounds. In this review we introduce the chemical diversity of bacterial volatiles, their antimicrobial activities and methods for testing this activity. Concluding, we discuss the possibility of using antimicrobial volatiles to antagonize the antimicrobial resistance crisis.

Simple Summary Monitoring animal behavior provides an indicator of their health and welfare. For this purpose, video surveillance is an important method to get an unbiased insight into behavior, as animals often show different behavior in the presence of humans. However, manual analysis of video data is costly and time-consuming. For this reason, we present a method for automated analysis using computer vision—a method for teaching the computer to see like a human. In this study, we use computer vision to detect red foxes and their body posture (lying, sitting, or standing). With this data we are able to monitor the animals, determine their activity, and identify their behavior. Abstract The behavior of animals is related to their health and welfare status. The latter plays a particular role in animal experiments, where continuous monitoring is essential for animal welfare. In this study, we focus on red foxes in an experimental setting and study their behavior. Although animal behavior is a complex concept, it can be described as a combination of body posture and activity. To measure body posture and activity, video monitoring can be used as a non-invasive and cost-efficient tool. While it is possible to analyze the video data resulting from the experiment manually, this method is time consuming and costly. We therefore use computer vision to detect and track the animals over several days. The detector is based on a neural network architecture. It is trained to detect red foxes and their body postures, i.e., ‘lying’, ‘sitting’, and ‘standing’. The trained algorithm has a mean average precision of 99.91%. The combination of activity and posture results in nearly continuous monitoring of animal behavior. Furthermore, the detector is suitable for real-time evaluation. In conclusion, evaluating the behavior of foxes in an experimental setting using computer vision is a powerful tool for cost-efficient real-time monitoring.

Simple Summary The tumor suppressor protein P53 is a major player in preventing liver cancer development and progression. In this study we could show that P53 negatively regulates the expression of Helicase, lymphoid specific (HELLS), previously described as an important pro-tumorigenic epigenetic regulator in hepatocarcinogenesis. The regulatory mechanism included induction of the P53 target gene P21 (CDKN1A) resulting in repression of HELLS via downregulation of the transcription factor Forkhead Box Protein M1 (FOXM1). Our in vitro and in vivo findings indicate an important additional aspect of the tumor suppressive function of P53 in liver cancer linked to epigenetic regulation. Abstract The major tumor suppressor P53 (TP53) acts primarily as a transcription factor by activating or repressing subsets of its numerous target genes, resulting in different cellular outcomes (e.g., cell cycle arrest, apoptosis and senescence). P53-dependent gene regulation is linked to several aspects of chromatin remodeling; however, regulation of chromatin-modifying enzymes by P53 is poorly understood in hepatocarcinogenesis. Herein, we identified Helicase, lymphoid specific (HELLS), a major epigenetic regulator in liver cancer, as a strong and selective P53 repression target within the SNF2-like helicase family. The underlying regulatory mechanism involved P53-dependent induction of P21 (CDKN1A), leading to repression of Forkhead Box Protein M1 (FOXM1) that in turn resulted in downregulation of HELLS expression. Supporting our in vitro data, we found higher expression of HELLS in murine HCCs arising in a Trp53−/− background compared to Trp53+/+ HCCs as well as a strong and highly significant correlation between HELLS and FOXM1 expression in different HCC patient cohorts. Our data suggest that functional or mutational inactivation of P53 substantially contributes to overexpression of HELLS in HCC patients and indicates a previously unstudied aspect of P53′s ability to suppress liver cancer formation.

Objective To analyze intensity-latency functions of intraoperative auditory evoked brainstem responses (ABRs) to stimulation by the Vibrant Soundbridge (VSB) active middle ear implant with respect to coupling efficiency, VSB evoked ABR thresholds, and coupling modality [oval window (OW) placement vs. Incus placement and vs. round window (RW) placement]. Study Design Exploratory study. Setting Bi-centric study at tertiary referral centers. Patients Twenty-four patients (10 female, 14 male, mean age: 58 years) who received a VSB. Outcome Measures Wave-V intensity-latency functions of intraoperative VSB evoked ABRs using a modified audio processor programmed to preoperative bone conduction thresholds for stimulation. Threshold level correction to coupling efficiency and ABR thresholds. Individual plots and exponential function fits. Results After ABR threshold level correction, the latency functions could be aligned. A large variance of latencies was observed at individual threshold level. Wave-V latency was longest in the Incus placement subgroup (9.73 ms, SD: 1.04) as compared to OW placement subgroup (9.47 ms, SD: 1.05), with the shortest latency in the RW placement subgroup (8.99 ms, SD: 0.68). For increasing stimulation levels, the variance decreased with intensity-latency function slopes converging toward a steady-state (saturation) latency caused by saturation of audio processor (stimulation) gain. Latency saturation was reached at a stimulation level of 50 dB nHL for the OW placement subgroup, 35 dB nHL for the Incus placement subgroup, and 30 dB nHL for the RW placement subgroup. The latency and saturation results indicated decreased dynamic range for RW placement, i.e., reverse stimulation. Conclusions VSB evoked ABR wave-V intensity-latency function slopes were similar to acoustic stimulation at high stimulation levels with a shift toward longer latencies caused by audio processor signal delay. Saturation of latencies occurred for higher stimulation levels due to saturation of audio processor gain. Thus, the analysis of VSB evoked intensity-latency functions appears to allow for the objective assessment of a patient's individual dynamic range. This can further improve diagnostics as well as intraoperative and postoperative quality control.

Sperm quantity and quality are key features explaining intra- and interspecific variation in male reproductive success. Spermatogenesis is sensitive to ionizing radiation and laboratory studies investigating acute effects of ionizing radiation have indeed found negative effects of radiation on sperm quantity and quality. In nature, levels of natural background radiation vary dramatically, and chronic effects of low-level background radiation exposure on spermatogenesis are poorly understood. The Chernobyl region offers a unique research opportunity for investigating effects of chronic low-level ionizing radiation on reproductive properties of wild organisms. We captured male bank voles (Myodes glareolus) from 24 locations in the Chernobyl exclusion zone in 2011 and 2015 and collected information on sperm morphology and kinetics. The dataset is limited in size and there overall was a relatively weak correlation between background radiation and sperm quality. Still, some correlations are worth discussing. First, mid-piece segments of spermatozoa tended to be smaller in bank vole males from areas with elevated background radiation levels. Second, we demonstrated a significant positive relationship between background radiation dose rates and the proportion of static spermatozoa among males within and among study locations after 10 as well as 60 min of incubation. Our results provide novel evidence of damaging effects of low dose ionizing radiation on sperm performance in wild rodent populations, and highlight that this topic requires further study across the natural gradients of background radiation that exist in nature.

Ongoing resistance developments against antibiotics that also affect last-resort antibiotics require novel antibacterial compounds. Strategies to discover such novel structures have been dimerization or hybridization of known antibacterial agents. We found novel antibacterial agents by dimerization of indols and hybridization with carbazoles. They were obtained in a simple one-pot reaction as bisindole tetrahydrocarbazoles. Further oxidation led to bisindole carbazoles with varied substitutions of both the indole and the carbazole scaffold. Both the tetrahydrocarbazoles and the carbazoles have been evaluated in various S. aureus strains, including MRSA strains. Those 5-cyano substituted derivatives showed best activities as determined by MIC values. The tetrahydrocarbazoles partly exceed the activity of the carbazole compounds and thus the activity of the used standard antibiotics. Thus, promising lead compounds could be identified for further studies.

The Study of Health in Pomerania (SHIP), a population-based study from a rural state in northeastern Germany with a relatively poor life expectancy, supplemented its comprehensive examination program in 2008 with whole-body MR imaging at 1.5 T (SHIP-MR). We reviewed more than 100 publications that used the SHIP-MR data and analyzed which sequences already produced fruitful scientific outputs and which manuscripts have been referenced frequently. Upon reviewing the publications about imaging sequences, those that used T1-weighted structured imaging of the brain and a gradient-echo sequence for R2* mapping obtained the highest scientific output; regarding specific body parts examined, most scientific publications focused on MR sequences involving the brain and the (upper) abdomen. We conclude that population-based MR imaging in cohort studies should define more precise goals when allocating imaging time. In addition, quality control measures might include recording the number and impact of published work, preferably on a bi-annual basis and starting 2 years after initiation of the study. Structured teaching courses may enhance the desired output in areas that appear underrepresented.

Background: Protease-activated receptor 1 (PAR1) and toll-like receptors (TLRs) are inflammatory mediators contributing to atherogenesis and atherothrombosis. Vorapaxar, which selectively antagonizes PAR1-signaling, is an approved, add-on antiplatelet therapy for secondary prevention. The non-hemostatic, platelet-independent, pleiotropic effects of vorapaxar have not yet been studied. Methods and Results: Cellular targets of PAR1 signaling in the vasculature were identified in three patient cohorts with atherosclerotic disease. Evaluation of plasma biomarkers (n = 190) and gene expression in endomyocardial biopsies (EMBs) (n = 12) revealed that PAR1 expression correlated with endothelial activation and vascular inflammation. PAR1 colocalized with TLR2/4 in human carotid plaques and was associated with TLR2/4 gene transcription in EMBs. In addition, vorapaxar reduced atherosclerotic lesion size in apolipoprotein E–knock out (ApoEko) mice. This reduction was associated with reduced expression of vascular adhesion molecules and TLR2/4 presence, both in isolated murine endothelial cells and the aorta. Thrombin-induced uptake of oxLDL was augmented by additional TLR2/4 stimulation and abrogated by vorapaxar. Plaque-infiltrating pro-inflammatory cells were reduced in vorapaxar-treated ApoEko mice. A shift toward M2 macrophages paralleled a decreased transcription of pro-inflammatory cytokines and chemokines. Conclusions: PAR1 inhibition with vorapaxar may be effective in reducing residual thrombo-inflammatory event risk in patients with atherosclerosis independent of its effect on platelets.

Growth, ageing and atherosclerotic plaque development alter the biomechanical forces acting on the vessel wall. However, monitoring the detailed local changes in wall shear stress (WSS) at distinct sites of the murine aortic arch over time has been challenging. Here, we studied the temporal and spatial changes in flow, WSS, oscillatory shear index (OSI) and elastic properties of healthy wildtype (WT, n = 5) and atherosclerotic apolipoprotein E-deficient (Apoe−/−, n = 6) mice during ageing and atherosclerosis using high-resolution 4D flow magnetic resonance imaging (MRI). Spatially resolved 2D projection maps of WSS and OSI of the complete aortic arch were generated, allowing the pixel-wise statistical analysis of inter- and intragroup hemodynamic changes over time and local correlations between WSS, pulse wave velocity (PWV), plaque and vessel wall characteristics. The study revealed converse differences of local hemodynamic profiles in healthy WT and atherosclerotic Apoe−/− mice, and we identified the circumferential WSS as potential marker of plaque size and composition in advanced atherosclerosis and the radial strain as a potential marker for vascular elasticity. Two-dimensional (2D) projection maps of WSS and OSI, including statistical analysis provide a powerful tool to monitor local aortic hemodynamics during ageing and atherosclerosis. The correlation of spatially resolved hemodynamics and plaque characteristics could significantly improve our understanding of the impact of hemodynamics on atherosclerosis, which may be key to understand plaque progression towards vulnerability.

Following the relational-developmental systems approach, this three-wave study examines whether acute stress (T2) mediates the relationship between the development of personality traits from the beginning of 8th grade (T1, Mage = 15.63, SD = 0.59; 22 girls) to the end of 9th grade (T3). Using the Montréal Imaging Stress Task, which is a task that provokes acute social stress by negative social feedback, this study combined the functional magnetic resonance imaging (fMRI), heart rate, and longitudinal survey data of 41 adolescents. Mediation analysis revealed that stress-induced left insula activation partially mediates the longitudinal stability of conscientiousness. These results highlight the impact of negative social feedback during stress on students’ personality development.

The Coronavirus disease 2019 (COVID-19) pandemic is affecting many areas of life and has led to major changes in undergraduate medical education. Even before the COVID-19 pandemic, high mental burden of medical students has frequently been reported in the literature. Additional pandemic-specific stressors could exacerbate this situation. This study aimed to assess mental health outcomes among medical students during the first semester after the COVID-19 outbreak and perception of the students on how the learning environment has changed. In May 2020, we conducted a cross-sectional survey among undergraduate medical students at a large medical school in Germany. The survey included validated mental health instruments (Distress Thermometer, Patient Health Questionnaire 4) and self-developed items to examine the perception of the study situation during the COVID-19 pandemic. Open-ended questions were analyzed by conventional content analyses. The response rate was 59.2% (914/1,545). Overall, 61.9% of the students reported distress levels above the cutoff. Year 1 students reported significantly higher levels of distress, anxiety and depression than students during their second to fourth year of studies. 48.3% of the students indicated a decrease in their study motivation since the beginning of the COVID-19 pandemic with significant differences between study years. The binary logistic regression model showed that male gender, being in study year 2, higher distress scores and higher symptoms of depression were significantly associated with a higher likelihood for experiencing serious worries. In the open-ended questions on current concerns related to the impact of the COVID-19 pandemic on their studies, students most frequently reported concerns about missing relevant practical learning experience, difficulties with self-regulated learning and self motivation as well as study-related worries. Year 4 students reported significantly more worries about the lack of practical training than students from study years 1 to 3. Analysis of gender differences showed that female students reported more frequently diverse worries. In contrast, female students shared more frequently helpful strategies in all the categories compared to male students. Our findings suggest that medical students experience significant levels of distress and mental burden during the COVID-19 pandemic and highlight the need for ongoing psychological and educational support for medical students during the COVID-19 pandemic and after.

Zusammenfassung Hintergrund: Craving wird als ein zentrales Merkmal der Sucht betrachtet und gilt gleichzeitig als entscheidende Determinante für Rückfälle bei Personen mit Abhängigkeitserkrankungen. Entsprechend wichtig ist daher die Bestimmung der individuellen Craving-Ausprägung während der medizinischen und psychotherapeutischen Behandlung. Da dies mit gängigen Selbstbeschreibungsfragebögen im Praxisalltag häufig wertvolle Zeit in Anspruch nimmt und Patienten mitunter auf inadäquate Weise überfordern bzw. sogar „triggern“ kann, wurde in der vorliegenden Studie statistisch geprüft, ob die Visuelle Analogskala (VAS) eine äquivalente und effiziente Alternative zu einem der gängigsten Fragebogenverfahren für die Bestimmung von Craving – der Obsessive Compulsive Drinking Scale (OCDS) – darstellt. Methode: Im Rahmen einer Äquivalenz- bzw. Noninferioritätsstudie basierend auf einer Fragebogenerhebung beantworteten N = 68 alkoholabhängige Patienten eines landesklinischen Zentrums für Psychiatrie in Baden-Württemberg die aus 14 Items bestehende OCDS und stuften parallel dazu ihr Trinkverlangen zu drei verschiedenen Messzeitpunkten auf einer VAS ein. Mithilfe der Statistiksoftware IBM® SPSS® Statistics und Minitab® wurden in einer computergestützten Datenanalyse bivariate Korrelationen, parametrische und nonparametrische Tests sowie Konfidenzintervalle berechnet, um statistisch evident zu zeigen, dass die über die VAS erhobenen Werte und die Ergebnisse aus der OCDS statistisch nicht voneinander abweichen bzw. nicht unterlegen sind. Ergebnisse: Sowohl die Äquivalenz- als auch die Noninferioritätshypothese wurde bestätigt: Das Konfidenzintervall 95% CI [– 0.38, 0.20] beim Test für verbundene Stichproben (Differenz = – 0.09, SD = 1.44, SE = 0.17) lag mit t (67) = 2.10, p = .02 für die untere Äquivalenzgrenze und t (67) = – 3.15, p < .01 für die obere Äquivalenzgrenze innerhalb des Äquivalenzintervalls. Ferner konnte gezeigt werden, dass das auf der VAS gemessene Trinkverlangen nach Bearbeitung der OCDS statistisch signifikant angestiegen war (p < .001, d = 0.12). Schlussfolgerung: Mit ihren Ergebnissen schafft die vorliegende Inaugural-Dissertation erstmals eine statistisch-wissenschaftliche Basis dafür, dass die VAS als effiziente Alternative neben der umfangreicheren und zeitaufwändigeren Fragebogendiagnostik (OCDS) in der Praxis nicht nur Anwendung finden kann, sondern auch zulässig ist. Schlüsselwörter: Äquivalenz – Obsessive Compulsive Drinking Scale (OCDS) – Visuelle Analogskala (VAS) – Craving – Alkohol

Drainage has commonly been a pre-requisite for the productive use of peatlands. The biased focus on agriculture, forestry and peat extraction has long ignored the destructive effects of drainage and the successive degradation of ecosystem functions of wet peatlands. Accelerated by the climate crisis, the finite nature of drainage-based peatland use is increasingly recognised. Consequently, productive land use options for wet or rewetted peatlands (paludiculture) are required as sustainable alternatives. A wide range of paludiculture plants and options of biomass utilisation are identified as suitable and promising. Despite the growing interest, experiences with and research on the economic viability of paludiculture are still rare. This thesis addresses the lack of knowledge on paludiculture in terms of practical feasibility, costs and benefits at the farm level, market prospects and framework conditions. I selected the two currently most advanced paludicultural practices in Europe: a) Harvesting natural reed beds as a traditional ‘low-input’ paludiculture, i. e. the utilisation of existing ‘wild’ vegetation stands; b) ‘Sphagnum farming’ as a novel ‘high-input’ paludiculture including stand establishment and water management required for the active transformation from drainage-based peatland use to paludiculture. In both cases, I investigate three different biomass utilisation avenues. This thesis adds to the fields of problem-driven sustainability and land-use science. Procedures and costs of paludiculture were studied in transdisciplinary research projects in close cooperation with practitioners. Due to the novelty of the topic, I put special emphasis on the triangulation of methods and data sources: pilot trials, field measurements, semi-structured expert interviews, structured questionnaires, secondary data from trade statistics and literature. To account for uncertainty related to costs and revenues, I conduct stochastic scenario analysis (Monte Carlo simulation) for the extended contribution margin accounting of harvesting reeds and sensitivity analysis for the investment appraisal of Sphagnum farming. Paludiculture on fens: harvesting reeds Paper I investigates harvesting procedures for reed-dominated (Phragmites australis) vegetation stands. In many European countries special-purpose tracked machinery is applied for large-scale conservation management and the commercial harvest of thatching reed. Stochastic scenario analysis reveals a wide range of possible economic outcomes (ca. € -1000 to € 1500 ha-1 a-1) and identifies material use of reed superior to its use as a source of energy. Winter harvest of high-quality thatching reed in bundles is the most profitable option. Winter harvest of bales for direct combustion is suitable for low-quality stands and has a limited risk of loss. In the case of summer harvest, revenues for green chaff for biogas production cannot cover harvesting costs but non-market income via subsidies and agri-environmental payments may ensure profitability. While biomass for energy generation is limited to a local market, thatching reed is traded as an international commodity. The market situation for thatching reed is investigated for Europe (Paper II) and Germany (Paper III). The major reed consuming countries in Western Europe (Netherlands, Germany, UK, Denmark) rely on imports of up to 85 % of the national consumption, with reed being imported from Eastern and Southern Europe and since 2005 also from China. The total market volume for reed for thatching in Northern Germany is estimated with 3 ± 0.8 million bundles of reed with a monetary value at sales prices of € 11.6 ± 2.8 million. Most of the thatchers (70 %) did not promote reed of regional origin to their customers due to insufficient availability in the first place and a lack in quality as second reason. The cultivation of reed in paludiculture may improve quantity and quality of domestic thatching reed. An area of 6000 ± 1600 ha with an average yield of 500 bundles per hectare would allow covering the current total demand of 3 million bundles of the German thatching reed market (Paper III). Paludiculture on bogs: Sphagnum farming Sphagnum farming provides an alternative to peatland degradation in two ways: Firstly, Sphagnum mosses can be cultivated as new agricultural crops on rewetted peatlands. Secondly, the produced Sphagnum biomass is a high-quality raw material suitable to replace peat in horticultural growing media (Paper V). Pilot trials have demonstrated the practical feasibility of establishing Sphagnum cultures on former bog grassland, cut-over bogs and mats floating on acidic waters bodies; Paper IV compares for the three types of production sites the specific procedures, costs and area potential in Germany. Water-based Sphagnum farming is not recommended for large-scale implementation due to highest establishment costs, major cultivation risks and limited area potential. For soil-based Sphagnum farming, the most important cost positions were Sphagnum shoots to set up pilots, investment for water management and regular weed management. Bog grassland has the highest area potential, i. e. 90,000 ha in NW Germany. Paper V assesses the profitability of Sphagnum farming on former bog grassland based on extrapolating five years of field experience data (establishment ņ management ņ harvest) to a total cultivation time of twenty years. Cultivating Sphagnum biomass as founder material for Sphagnum farming or restoration was profitable even in pessimistic scenarios with high costs, high bulk density and low yields. Selling Sphagnum for orchid production was economically viable in the case of medium to high yields with a low bulk density. Cost-covering prices for Sphagnum biomass substituting peat seem achievable if end consumers pay a surcharge of 10 % on the peat-free cultivated horticultural end-product. An area of 35,000 ha of Sphagnum farming suffices to meet the annual demand of the German growing media industry for slightly decomposed Sphagnum peat. Framework conditions affecting feasibility of paludiculture The relation of revenues from selling biomass to its production costs is an important piece of the paludiculture feasibility puzzle. Further aspects effecting the economic viability and competitiveness of paludiculture encompass the market demand, the availability of mature technology, legal restrictions, the eligibility for agricultural subsidies, a remuneration of external benefits and the opportunity costs of present farming activities (Paper I, V). Legal and policy regulations are of major importance for land use decisions on peatlands – both for keeping up drainage and for shifting to paludiculture. Conclusion and Outlook This thesis provides a first assessment of the costs and profitability of large-scale harvesting of reeds and Sphagnum farming based on real-life data. The paludicultural practices investigated may be a solution for a minor share of the more than 1 million ha of peatlands drained for agriculture in Germany. Future research should also address other biomass utilisation options and other crops. Large-scale pilots are required to improve technical maturity of procedures and machinery, gather reliable data to replace assumptions on costs and revenues and study long-term effects on economics and ecosystem services. The micro-economic perspective needs to be complemented by the societal perspective quantifying and monetising external effects of peatland restoration, paludiculture and drainage-based peatland use. There is a high need for intensified research, large-scale implementation and accelerated adaption of the policy and legal framework to develop paludiculture as an economically viable option for degraded peatlands.

Die Notwendigkeit einer plastisch chirurgischen Rekonstruktion der weiblichen Brust ist in fast allen Fällen auf eine zuvor diagnostizierte Brustkrebserkrankung oder prämaligne Erkrankung, die eine Mastektomie erforderte, zurückzuführen. Hierbei wird die natürliche Form der Brust zusammen mit dem Mammillen-Areola-Komplex nachgebildet. Da eine haut- oder nippelsparende Mastektomie durch den amputierenden Eingriff nur einen dünnen Brusthautmantel zurücklässt, ist die Einlage einer subpectoralen Prothese sinnvoll. Der Musculus pectoralis major ist durch die Implantateinlage in seiner Dimension verkürzt und vermag den unteren Brustpol nicht hinreichend abzudecken. Somit kann eine komplette und sichere Prothesenbedeckung nicht mehr gewährleistet werden. Die Nachteile einer subpectoralen Implantateinlage können durch die Einlage abdeckender und gleichzeitig stützender Fremdmaterialien, wie die hier verwendeten Alloplasten TiLOOP® Bra und SERAGYN® BR sowie durch die porcine azelluläre Dermis Strattice™ revidiert werden. Trotz dessen sich bislang kaum vergleichbare publizierte Studien in der Literatur zum Thema Alloplasten- und Dermisvergleich finden, ist die Vergleichbarkeit der Ergebnisse durch gesonderte Untersuchungen der einzelnen Interponate in anderen Publikationen gesichert. Der Behandlungserfolg und das ästhetisch zufriedenstellende sowie onkologisch sichere Ergebnis wurde in dieser Arbeit anhand der dokumentierten Komplikationsraten gemessen. Hierbei wurde wie in der Literatur beschrieben zwischen „major und minor complications“ unterschieden.41 
Beim Vergleich der jeweiligen Komplikationsarten besteht Komparabilität zwischen der herrschenden Literatur und den Ergebnissen bei den SERAGYN® BR- und TiLOOP® Bra-Populationen in der Universitätsmedizin Greifswald. Mit einer „major complications“–Rate von 11,1 % bei den mit SERAGYN® BR rekonstruierten Mammae und 14,9 % in der TiLOOP® Bra-Population ist ein akzeptables Ergebnis erzielt worden. Auch bei den „minor complications“ stellt die Rate von 13 % in der SERAGYN® BR-Population und 9,6 % bei den mit dem TiLOOP® Bra rekonstruierten Brüsten einen guten Schnitt im Behandlungserfolg dar. Die azelluläre Dermis Strattice™ erzielte mit jeweils 27,5 % „major“ und „minor complications“ die schlechteren Ergebnisse zum einen im Vergleich mit dem Therapieerfolg der anderen Populationen und zum anderen in Äquivalenz zur herrschenden Literatur.
Es konnte demonstriert werden, dass sich der Einsatz der azellulären Dermis nicht für die vorgeschädigte Brust im Sinne von zweizeitigen Operationsverfahren, sowie in Verbindung mit spezifischen Risikofaktoren eignet und besonders unter dem Einfluss einer Strahlentherapie eine erhöhte Komplikationsrate zu verzeichnen ist.
Auch im Zusammenhang mit plastisch rekonstruierenden Operationen gemeinsam mit dem TiLOOP® Bra oder dem Alloplasten SERAGYN® BR musste ein Anstieg von postoperativen Komplikationen dokumentiert werden, wenn eine Bestrahlung des Operationsgebietes vorgenommen wurde. Um eine optimale und möglichst komplikationsarme operative Nachbildung der weiblichen Brust nach Ablatio erzielen zu können, bedarf es einer engen Indikationsstellung sowie Risiko-Nutzen-Abwägungen, die jedwede patientinneneigenen und iatrogenen Risikofaktoren berücksichtigt und handhaben kann. Ziel ist es dabei, trotz Risikofaktoren eine optimierte Versorgung der Patientinnen zu gewährleisten und so sichere sowie ästhetisch einwandfreie Ergebnisse erzielen zu können. Dazu gehören prüfende Überlegungen welches der Interponate die bestmögliche Kompatibilität zur geplanten Rekonstruktionsart aufweist und zudem die individuellen Patientinnenmerkmale berücksichtigen kann. Ist aufgrund des Tumorstadiums eine Bestrahlung der Thoraxwand notwendig, sollte der Patientin eine Rekonstruktion mit Eigengewebe (z.B. TRAM- oder DIEP-Lappen) empfohlen werden.28 Bei Erfordernis einer Radiatio muss von einer implantatgestützten Brustrekonstruktion in Verbindung mit Netzen oder einer azellulären Dermis abgeraten werden. Sollte die Patientin dennoch ausdrücklich einen Wiederaufbau mittels Implantaten und Netzen bzw. ADM wünschen, besteht die Notwendigkeit auf das erhöhte postoperative Risiko hinzuweisen und ausführlich aufzuklären. Obwohl diese retrospektive Studie keinen vollen Eingriff in die Indikationsstellung bieten kann, so werden bereits Anhaltspunkte für eine ideale Interponatauswahl offeriert, um eine optimale Rekonstruktion mit einem niedrigen Risikoprofil für postoperative Komplikationen und ein hohes Maß an Patientinnenzufriedenheit zu gewährleisten.

ObjectivesTo investigate levels of distress, depression, anxiety, stress and perception of their current study situation during the COVID-19 pandemic among undergraduate dental and medical students.DesignObservational, cross-sectional study including two consecutive surveys (May and July 2020).SettingA large medical school in Germany.ParticipantsAll first year dental and medical students were invited. 132 participating first year students (44 dental, 88 medical) from the first survey and 150 students (50 dental, 100 medical) from the second were included in our analyses.Primary and secondary outcome measuresMental burden (distress thermometer, Patient Health Questionnaire-4, Perceived Stress Scale-4) and self-reported changes in mental health and perception of study situation during the COVID-19 pandemic (self-developed items) were compared. Open-ended questions were analysed by conventional content analyses.ResultsA considerable proportion of students (t1: May 2020: 84.1%; t2: July 2020: 77.3%) reported distress levels above cut-off. In July 2020, dental students reported significantly higher distress scores than medical students (dental: M=7.0, SD=2.3; medical: M=5.7; SD=2.1; p<0.001). More dental than medical students reported mild, moderate and severe levels of anxiety and depression symptoms. The majority stated that their mental health and study motivation had not changed during the pandemic. Logistic regression showed that being a dental student was significantly associated with a higher likelihood for serious worries regarding the study situation during COVID-19 at t1 (OR 4.0; 95% CI 1.1 to 14.2). At t2 higher distress was significantly associated with a higher likelihood for experiencing serious worries (OR 1.8; 95% CI 1.3 to 2.5). Regarding current concerns related to the pandemic, students most frequently reported difficulties with self-regulated learning (15.2%), study-related worries and uncertainty (14.4%), missing feedback of students and lecturers (11.4%) and lack of practical training (9.8%).ConclusionThe results suggest that high mental burden and the lack of practical training among medical and dental students is an increasing problem, with a possibly even higher urgency in dental students. Tailored psychological and educational support offers during and after the COVID-19 pandemic might help them as they progress through (medical and) dental school.