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Introduction Up to a third of women worldwide report having experienced an act of sexual violence during their lifetime. The emergency gynecology department is often the first port of call for affected individuals. The aim of the current study was to evaluate the importance of gynecology examinations for women after a sexual offense and to evaluate the pattern of injuries sustained. Methods This study is a retrospective single center analysis of the gynecology and forensic examination reports of all women examined for a suspected sexual offense in the central emergency department of a university hospital between 2013 and 2017 (n = 692). We evaluated genital and extragenital injury patterns, age, offender profile, time of offense, and substance use, as well as the administration of post-coital contraception and post-exposure prophylaxis for HIV. Results The affected individuals had a mean age of 26 (12 – 91 years). Almost 75% of affected individuals presented within 24 hours of the reported sexual offense. Extragenital injuries were detected in 78.6% of patients and genital injuries in 28.5%. Overall, 20.1% of the women reported complete memory loss and 18.7% partial memory loss of the actual event. Risk factors for memory lapse were the consumption of alcohol and/or the (possibly non-consensual) administration of other substances acting on the central nervous system. A history of alcohol consumption by the victim (hazard ratio [HR] 1.95; 95% confidence interval [CI] 1.21 – 3.12, p = 0.006) and younger victims aged between 25 – 49 years (HR 1.75; 95% CI 1.07 – 2.85, p = 0.025) were associated with the occurrence of extragenital injuries. However, if the perpetrator was someone who was known to the affected individual, fewer extragenital injuries were sustained (HR 0.60; 95% CI 0.36 – 0.99, p = 0.046). Reports of genital injuries, associated with an older age of affected individuals and indications of anal penetration, resulted in more frequent administration of post-exposure prophylaxis (29.1% vs. 19.5%, p Conclusion Emergency gynecology examinations form a fundamental component of the medical care and the assessment of affected women after a sexual offense, since almost a third of victims sustain injuries to the genital region. In addition to a detailed complete physical examination and expert forensic documentation of physical and genital injuries, victims should also be offered psychological support which is easy for them to access.

Multiple consensus statements have called for preclinical randomized controlled trials to improve translation in stroke research. We investigated the efficacy of an interleukin-17A neutralizing antibody in a multi-centre preclinical randomized controlled trial using a murine ischaemia reperfusion stroke model. Twelve-week-old male C57BL/6 mice were subjected to 45 min of transient middle cerebral artery occlusion in four centres. Mice were randomly assigned (1:1) to receive either an anti-interleukin-17A (500 µg) or isotype antibody (500 µg) intravenously 1 h after reperfusion. The primary endpoint was infarct volume measured by magnetic resonance imaging three days after transient middle cerebral artery occlusion. Secondary analysis included mortality, neurological score, neutrophil infiltration and the impact of the gut microbiome on treatment effects. Out of 136 mice, 109 mice were included in the analysis of the primary endpoint. Mixed model analysis revealed that interleukin-17A neutralization significantly reduced infarct sizes (anti-interleukin-17A: 61.77 ± 31.04 mm3; IgG control: 75.66 ± 34.79 mm3; P = 0.01). Secondary outcome measures showed a decrease in mortality (hazard ratio = 3.43, 95% confidence interval = 1.157–10.18; P = 0.04) and neutrophil invasion into ischaemic cortices (anti-interleukin-17A: 7222 ± 6108 cells; IgG control: 28 153 ± 23 206 cells; P < 0.01). There was no difference in Bederson score. The analysis of the gut microbiome showed significant heterogeneity between centres (R = 0.78, P < 0.001, n = 40). Taken together, neutralization of interleukin-17A in a therapeutic time window resulted in a significant reduction of infarct sizes and mortality compared with isotype control. It suggests interleukin-17A neutralization as a potential therapeutic target in stroke.

Purpose Comorbidities and polypharmacy are risk factors for worse outcome in stroke. However, comorbidities and polypharmacy are mostly studied separately with various approaches to assess them. We aimed to analyze the impact of comorbidity burden and polypharmacy on functional outcome in acute ischemic stroke (AIS) patients undergoing mechanical thrombectomy (MT). Methods Acute ischemic stroke patients with large vessel occlusion (LVO) treated with MT from a prospective observational study were analyzed. Relevant comorbidity burden was defined as a Charlson Comorbidity Index (CCI) score ≥ 2, polypharmacy as the intake of ≥ 5 medications at time of stroke onset. Favorable outcome was a score of 0–2 on the modified Rankin scale at 90 days after stroke. The effect of comorbidity burden and polypharmacy on favorable outcome was studied via multivariable regression analysis. Results Of 903 patients enrolled, 703 AIS patients (mean age 73.4 years, 54.9% female) with anterior circulation LVO were included. A CCI ≥ 2 was present in 226 (32.1%) patients, polypharmacy in 315 (44.8%) patients. Favorable outcome was less frequently achieved in patients with a CCI ≥ 2 (47, 20.8% vs. 172, 36.1%, p p p = 0.005), while polypharmacy was not (OR 0.81, 95% CI 0.52–1.27, p = 0.362). Conclusion Relevant comorbidity burden and polypharmacy are common in AIS patients with LVO, with comorbidity burden being a risk factor for poor outcome.

ZusammenfassungMehrere Studien belegen den hohen beruflichen Stress von Ärzten und Ärztinnen bis hin zu Burnout-Symptomen. Untersucht In der vorliegenden Studie wurde das Belastungserleben von Ärzten und Ärztinnen im längsschnittlichen Verlauf der fachärztlichen Weiterbildung untersucht. Dazu wurde der Frage nachgegangen, wie sich das Burnouterleben unter Berücksichtigung von Gratifikationskrisen von Beginn bis zum Ende der Weiterbildung an innerhalb von 6 Jahren verändert und ob es jeweils einen Einfluss von Geschlecht und Elternstatus gibt. Die Datenerhebung erfolgte im Rahmen der KarMed Studie. Eingesetzt wurden das Maslach Burnout Inventar (MBI-HSS (MP)) und der Effort-Reward-Imbalance Fragebogen (ERI). Die theoretischen Annahmen wurden in allgemeinen linearen Modellen und allgemeinen linearen gemischten Modellen mit Meßwiederholungsdesign statistisch überprüft. Es bestand ein hoher Zusammenhang zwischen dem Ausgangsniveau der Belastung zu Beginn der Weiterbildung und dem Belastungserleben zum Ende der Weiterbildung. Gratifikationskrisen hatten einen signifikanten Einfluss auf die Sub-Skala emotionale Erschöpfung des MBI, nicht aber auf die Subskalen persönliche Leistungsfähigkeit und Depersonalisation. Signifikante Zeiteffekte fanden sich auf allen 3 Sub-Skalen des MBI, mit signifikanten Geschlechtseffekten auf den Subskalen emotionale Erschöpfung und Depersonalistaion. Der Elternstatus weist unter Berücksichtigung der Burnout-Verlaufswerte und Gratifikationskrisen keinen signifikanten Einfluss auf das Burnouterleben auf. Die theoretischen Implikationen und die praktischen Konsequenzen für die Gesundheitsförderung von ÄrztInnen werden ebenso diskutiert wie die Begrenzungen der Untersuchung.

Background Sedative premedication with benzodiazepines has been linked with prolonged recovery and inadequate emergence during the immediate postoperative period. We aimed to analyze the association between postanesthesia care unit (PACU) delirium and sedative premedication with oral midazolam. Methods We performed a secondary analysis of prospectively collected data before (midazolam cohort) and after (non-midazolam cohort) implementation of a restrictive strategy for oral premedication with midazolam. From March 2015 until July 2018, we included patients 60 years and older, who underwent elective radical prostatectomy for prostate cancer. Exclusion criteria were contraindications to premedication with midazolam, preoperative anxiety, and a history of neurological disorders. Patients, who were scheduled for postoperative admission to the intensive care unit, were excluded. Between 2015 and 2016, patients received 7.5 mg oral midazolam preoperatively (midazolam cohort). Patients included between 2017 and 2018 did not receive any sedative medication preoperatively (non-midazolam cohort). The primary endpoint was the incidence of PACU delirium. Results PACU delirium rates were 49% in the midazolam cohort (n = 214) and 33% in the non-midazolam cohort (n = 218). This difference was not statistically significant on multivariable logistic regression analysis (OR 0.847 [95% CI 0.164; 4.367]; P = 0.842). Age (OR 1.102 [95% CI 1.050; 1.156]; P < 0.001), the cumulative dose of sufentanil (OR 1.014 [95% CI 1.005; 1.024]; P = 0.005), and propofol-sufentanil for anesthesia maintenance (OR 2.805 [95% CI 1.497; 5.256]; P = 0.001) were significantly associated with PACU delirium. Conclusion Midazolam for sedative premedication was not significantly associated with PACU delirium. The reduction in the incidence of PACU delirium throughout the study period may be attributable to improvements in perioperative management other than a more restrictive preoperative benzodiazepine administration.

Postinduction and intraoperative hypotension are associated with organ injury in non-cardiac surgery patients. Automated ambulatory blood pressure monitoring can identify chronic arterial hypertension and nocturnal blood pressure non-dipping. We tested the hypotheses that: a) chronic arterial hypertension and nocturnal non-dipping are independent risk factors for postinduction and intraoperative hypotension; and b) adding information on chronic arterial hypertension and nocturnal non-dipping improves hypotension prediction models based on readily available preoperative clinical information.Prediction model development based on a secondary analysis of a prospective observational study.German university medical center.366 non-cardiac surgery patients who had preoperative automated ambulatory blood pressure monitoring.Multivariable analyses to identify risk factors for postinduction and intraoperative hypotension. Area under receiver operating characteristics curves (AUROC) and likelihood-ratio tests to test whether adding information on chronic arterial hypertension and nocturnal non-dipping improves hypotension prediction models based on readily available preoperative clinical information.Risk factors for postinduction hypotension were age in years (odds ratio: 1.06 (95% confidence interval: 1.03 to 1.10), P = 0.001), American Society of Anesthesiologists physical status class (1.85 (1.02 to 3.35), P = 0.043), preoperative use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (15.19 (1.76 to 131.46), P = 0.013), chronic arterial hypertension (2.54 (1.49 to 4.34), P = 0.001), and nocturnal non-dipping (3.61 (2.09 to 6.23), P 0.001). The model's AUROC was 0.76 (95% confidence interval: 0.71 to 0.81) with and 0.67 (0.62 to 0.73) without information on chronic arterial hypertension and nocturnal non-dipping (P 0.001). Risk factors for intraoperative hypotension were male sex (1.73 (1.07 to 2.80), P = 0.025), chronic arterial hypertension (4.35 (2.33 to 8.14), P 0.001), and nocturnal non-dipping (3.56 (2.07 to 6.11), P 0.001). The model's AUROC was 0.76 (0.70 to 0.81) with and 0.63 (0.57 to 0.69) without information on chronic arterial hypertension and nocturnal non-dipping (P 0.001).Chronic arterial hypertension and nocturnal non-dipping are independent risk factors for postinduction and intraoperative hypotension in non-cardiac surgery patients. Adding information on chronic arterial hypertension and nocturnal non-dipping moderately improved hypotension prediction models based on preoperative clinical information.

Background Studies investigating the longitudinal predictive value of burnout on both effort-reward imbalance (within the working place) and work-family conflict (between work and private life) in residents are lacking. Former cross-sectional studies showed an association of effort-reward imbalance and work family conflict with an elevated burnout risk in physicians. Methods Data acquisition was carried out within the multi-centric, longitudinal, and prospective “KarMed” study in Germany from 2009 until 2016. Yearly surveys including validated scales: the Maslach Burnout Inventory with its three subscales (emotional exhaustion, personal accomplishment, depersonalisation), the Work-Family Conflict Scale, and the Effort-Reward Imbalance Inventory. Further independent variables were gender and parental status.The analyses were based on general linear models and general linear mixed models with repeated measures designs. Results Significant time-fixed effects were found for all three subscales of the Maslach Burnout Inventory, with gender effects on the subscales emotional exhaustion and depersonalisation. The parental status had no significant effect on burnout. All estimated means for burnout during 6 years of post-graduate training were higher when work-family conflict and gratification crisis were taken into account. Personal accomplishment increased continuously over time as well showing neither gender differences nor influences by the parental status. Conclusions Personal accomplishments might act as a buffer compensating to some extent for the physicians’ stress experience. Given that burnout may be associated with poor patient care, there is a need to reduce burnout rates and their associated factors in resident physicians.

Several studies have demonstrated high work related stress and burnout symptoms in physicians. The study examined the longitudinal relationships of burnout and gratification crisis during 6 years of postgraduate medical education, controlled for gender and parental status. Data acquisition was carried out within the KarMed-study. Administered were the Maslach Burnout Inventory (MBI-HSS (MP)) (MBI) and the Effort-Reward-Imbalance (ERI). The analyses focused on general linear models and general linear mixed models with repeated measure designs. The amount of burnout perceived at the beginning of the postgraduate medical education is highly associated with the perceived amount of burnout at the end. Gratification crisis were significant for one subscale of the MBI (emotional exhaustion), yet not for personal accomplishment nor depersonalization. Significant time effects were found on all 3 subscales of the MBI, with gender effects on the subscales emotional exaustion and depersonalization. Having kids did not have significant effects, controlled for all measurement points of burnout as well as for gratification crisis. Theoretical implications and practical consequences for doctors, as well as the limitations of the study, are discussed.Mehrere Studien belegen den hohen beruflichen Stress von Ärzten und Ärztinnen bis hin zu Burnout-Symptomen. Untersucht In der vorliegenden Studie wurde das Belastungserleben von Ärzten und Ärztinnen im längsschnittlichen Verlauf der fachärztlichen Weiterbildung untersucht. Dazu wurde der Frage nachgegangen, wie sich das Burnouterleben unter Berücksichtigung von Gratifikationskrisen von Beginn bis zum Ende der Weiterbildung an innerhalb von 6 Jahren verändert und ob es jeweils einen Einfluss von Geschlecht und Elternstatus gibt. Die Datenerhebung erfolgte im Rahmen der KarMed Studie. Eingesetzt wurden das Maslach Burnout Inventar (MBI-HSS (MP)) und der Effort-Reward-Imbalance Fragebogen (ERI). Die theoretischen Annahmen wurden in allgemeinen linearen Modellen und allgemeinen linearen gemischten Modellen mit Meßwiederholungsdesign statistisch überprüft. Es bestand ein hoher Zusammenhang zwischen dem Ausgangsniveau der Belastung zu Beginn der Weiterbildung und dem Belastungserleben zum Ende der Weiterbildung. Gratifikationskrisen hatten einen signifikanten Einfluss auf die Sub-Skala emotionale Erschöpfung des MBI, nicht aber auf die Subskalen persönliche Leistungsfähigkeit und Depersonalisation. Signifikante Zeiteffekte fanden sich auf allen 3 Sub-Skalen des MBI, mit signifikanten Geschlechtseffekten auf den Subskalen emotionale Erschöpfung und Depersonalistaion. Der Elternstatus weist unter Berücksichtigung der Burnout-Verlaufswerte und Gratifikationskrisen keinen signifikanten Einfluss auf das Burnouterleben auf. Die theoretischen Implikationen und die praktischen Konsequenzen für die Gesundheitsförderung von ÄrztInnen werden ebenso diskutiert wie die Begrenzungen der Untersuchung.

There has been an increasing number of emergency department (ED) visits recently. It is unclear whether, in addition to a shift in services from the outpatient to the inpatient sector, other causes, (e. g. environmental factors), play a role. The aim was to investigate associations between the number of cardiovascular and respiratory ED visits and environmental variables.Highly correlated environmental data were subjected to a principal component analysis. By using cross-correlation functions, environmental variables with time lags that showed the highest correlation with the number of ED visits were taken into consideration in the UNIANOVA analysis model, together with, among others, the day of the week and interaction terms.The final regression model explained 47% of the variation in respiratory ED visits demonstrating main effects for Mondays (B=10.69; p0.001). Season showed significant effects with highest ED visits in autumn. No direct associations between environmental variables and number of respiratory ED visits were found. The results for the cardiovascular outcome were less expressive (RThe results suggest that weekdays had the main effect on ED visits. In future, we will collect and analyze environmental data at the micro level to achieve a higher model quality and better interpretability.In den letzten Jahren ist eine zunehmende Anzahl von Notfallaufnahmen zu beobachten. Unklar ist, ob neben einer Leistungsverlagerung vom ambulanten in den stationären Sektor auch andere Ursachen, wie sich verändernde Umweltfaktoren, relevant sind. Ziel der Arbeit war, Zusammenhänge der Anzahl kardiovaskulärer und respiratorischer Notfallaufnahmen mit Umweltvariablen zu untersuchen.Hochkorrelierte Umweltdaten wurden in eine Faktorenanalyse einbezogen. Durch Kreuzkorrelationsfunktionen wurden die Umweltvariablen mit Zeitverzögerungen, die die höchste Korrelation mit der Anzahl der Notfallaufnahmen zeigten, in Modellanalysen u. a. zusammen mit Wochentag und Interaktionen berücksichtigt.Das finale Regressionsmodell erklärte 47% der Variation der respiratorischen Notfallaufnahmen, die Haupteffekte mit den höchsten Notfallaufnahmen am Montag zeigten (B=10,69; p0,001). Für die Jahreszeit zeigten sich signifikante Einflüsse mit höchsten Notfallaufnahmen im Herbst. Die Daten zeigten keine direkten Zusammenhänge zwischen Umweltvariablen und Anzahl der respiratorischen Notfallaufnahmen. Ergebnisse der kardiovaskulären Analysen waren weniger aussagekräftig (RDie Ergebnisse deuten darauf hin, dass der Wochentag den größten Einfluss auf kardiovaskuläre und respiratorische Notfallaufnahmen in Hamburg hat. Künftig sollen Umweltdaten auf Mikroebene erhoben und für weitere Analysen genutzt werden, um eine höhere Modellgüte und bessere Interpretierbarkeit zu erreichen.

Background and Purpose Phosphodiesterases (PDEs) are important regulators of β‐adrenoceptor signalling in the heart. While PDE4 is the most important isoform that regulates ICa,L and force in rodent cardiomyocytes, the dominant isoform in adult human cardiomyocytes is PDE3. Experimental Approach Given the potential of human‐induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) for biomedical research, this study characterized the contribution of PDE3 and PDE4 isoforms to the regulation of ICa,L and force in hiPSC‐CMs in an engineered heart tissue (EHT) model. Key Results There was a lower abundance of mRNA for PDE3A and 4A in hiPSC‐CM EHT than in non‐failing human heart samples. Selective inhibition of PDE3 and 4 with cilostamide and rolipram, respectively, showed that, in hiPSC‐CM, PDE4 was the predominant isoform for the regulation of ICa,L (cilostamide: +1.44‐fold; rolipram: +1.77‐fold). Furthermore, in contrast to cilostamide, rolipram decreased the EC50 of isoprenaline about 15‐fold. Conclusion and implications The predominance of PDE4 over PDE3 is a peculiarity of hiPSC‐CMs and is probably an indicator of immaturity. This finding has implications for the use of hiPSC‐CM as pharmacological models to investigate and assess the effects of PDE inhibitors.

Sygdomme i planter kan være forårsaget af mange forskellige mikroorganismer, og ofte vil der i en enkelt afgrøde og på én plante være flere arter tilstede samtidigt. På trods af denne erfaring har der været tradition for at forske i sygdomme enkeltvis, og betydningen på det totale sygdomsniveau af vekselvirkninger mellem de enkelte patogener er kun blevet studeret i begrænset omfang. Her beskrives vekselvirkningen mellem sygdommene bladplet og skoldplet på byg i markforsøg.

Disease assessment is the basis for describing disease resistance characteristics of commercial varieties in national variety lists for all crops where disease is considered a problem. It is well known that ‘disease’ in a specific situation depends on a whole range of interacting hosts, pathogens and environmental conditions. However, the biological complexity conflicts with the wish to express disease resistance characteristics of a variety as a single score per disease. This problem will be illustrated by basic dynamics of growth and senescence of both host and pathogen over time. Disease expressed in terms of absolute diseased leaf area, disease relative to total leaf area or green leaf area will be discussed in general. Two particular problems in low-input systems will be discussed, i.e. increased variability in nutritional status in field plots, which may influence the balance between abiotic and biotic stresses (diseases) and interact with disease on individual varieties, as well as the influence of weeds and diverse crops (variety mixtures and composite cross populations). The presence of disease in organic and low-input cropping systems may be underestimated because abiotic stresses, which enhance a general senescence of leaves, may obscure disease assessment, in particular disease on leaves. Weeds may interact by harbouring disease showing similar symptoms as on the target crop, or by ‘diluting’ disease by additional healthy green leaf area of the ‘crop’ like in a variety mixture. Other general topics such as differences between host/pathogen systems, timing of assessment, assessment scale, and interpretation and analysis of data are also discussed.