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A Precise Synthetic Toolbox: H-Bond-Assisted Quadruple Reactivity of o-Dimethylaminoaryloximes
Get PDFNon-covalent interactions are a highly promising tool for the development of transition-metal-free chemospecific synthetic transformations. Here, we demonstrate the implementation of non-covalent interactions as a simple, precise, and flexible synthetic toolbox, allowing the controlled transformation of o-dimethylaminoaryloximes into nitriles and hard-to-reach nitrogen heterocycles under mild conditions. This diverse reactivity is activated via hydrogen bonding and facilitated via the “buttressing effect” of the substituents next to the NMe2 group. All transformations require only simple and easily available acids and solvents, which generally provide precise control over the direction of the reaction, allowing the selective synthesis of nitriles, fused pyrazoles, isoxazoles, and pyrroles
Coherent suppression of high harmonics in Dirac materials
Get PDFHigh-harmonic generation in solids by intense laser pulses provides a fascinating platform for studying ultra-fast electron dynamics and material properties, where the coherent character of the electron dynamics is a central aspect. Using the semiconductor Bloch equations, we expound a mechanism suppressing the high harmonic spectrum arising from the coherent superposition of intra- vs inter-band contributions to the total signal. We provide evidence for the generality of this phenomenon by extensive numerical simulations exploring the parameter space of this coherent suppression of high harmonics in systems of massive Dirac Fermions. We supplement our numerical observations with analytical results for the one-dimensional case. Moreover, we demonstrate reentrant behavior of suppressed high harmonics upon increasing dephasing
Cardioprotective effects of semaglutide on isolated human ventricular myocardium
Get PDFAims
Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has shown promising effects in reducing cardiovascular events in patients with obesity and heart failure (HF) with preserved ejection fraction (HFpEF) irrespective of concomitant diabetes. However, the exact mechanisms underlying its cardioprotective actions remain unclear. Our study investigates the direct effects of semaglutide on human cardiomyocytes, focusing on calcium (Ca) and sodium (Na) handling and its potential to improve myocardial contractility.
Methods and results
Human left ventricular cardiomyocytes were isolated from non-failing (NF) hearts, patients with aortic stenosis and a HFpEF-like phenotype (AS), and those with end-stage HF with reduced ejection fraction (HFrEF). Late Na current (INa), sarcoplasmic reticulum (SR) Ca leak, and contractility were assessed in isolated cardiomyocytes treated with semaglutide. CaMKII inhibitor autocamtide-2-related inhibitory peptide and GLP-1 receptor antagonist exendin 9–39 (Ex-9-39) were used to elucidate signalling pathways. Semaglutide reduced late INa in AS and HFrEF cardiomyocytes to levels comparable to NF. Additionally, semaglutide decreased diastolic SR Ca leak and improved systolic Ca transients and contractility in AS and HFrEF tissue. These effects were mediated through GLP-1 receptor agonism and were comparable to CaMKII inhibition. In multicellular preparations, semaglutide differentially improved myocardial contractility in AS and HFrEF in a dose-dependent manner.
Conclusion
Semaglutide directly modulates ion homeostasis in human cardiomyocytes, reducing proarrhythmic diastolic SR Ca leak and enhancing systolic function, which may explain its observed clinical benefits. These findings provide mechanistic insights into the cardioprotective effects of semaglutide and suggest its potential therapeutic use in
Survival and risk factor analysis in patients with septic arthritis: a retrospective study of 192 cases
Get PDFBackground
Septic arthritis (SA) presents a complex clinical challenge, often resulting in significant morbidity and mortality. This study aimed to (1) assess overall mortality rates and (2) identify potential factors contributing to increased mortality risk in patients with SA.
Methods
This retrospective study on SA patients treated at a German university hospital between January 1, 2011, and December 31, 2021. Patients were identified using International Classification of Diseases (ICD)-10 codes for septic arthritis, specifically “M00.-”. The study evaluated mortality rates and analyzed comorbidities, pathogens, and other potential risk factors. Kaplan–Meier survival curves and odds ratios (OR) were calculated to assess mortality risk.
Results
In a cohort of 192 patients diagnosed with SA, 64 patients (33.3%) died during a mean follow-up period of 54.4 ± 42 months. The overall mortality rate was 17.5% at one year, 19.9% at two years, and 28.3% at five years. Patients aged 65 years or older, as well as those with arterial hypertension, congestive heart failure, chronic renal disease, chronic liver disease, malignancy, steroid use and immunosuppression showed significantly higher mortality rates (p < 0.05). Chronic renal disease (OR = 2.80), malignancy (OR = 3.40), and chronic heart failure (OR = 2.62) were identified as significant notably risk factors for mortality.
Conclusion
This study highlights a notably high mortality rate among vulnerable patients with SA, particularly those with pre-existing comorbidities. Recognizing and addressing these risk factors early could improve patient outcomes. These results unterscore the need for close monitoring of SA patients, particularly those with chronic organ conditions, and timely intervention for sepsis to reduce mortality risk
Aufbau eines Modellsystems zur Untersuchung strömungsinduzierter Akkumulation plasmatischer Proteine
Get PDFIm Rahmen von ECMO-Therapien stellen Blutungen und thrombotische Ereignisse ein noch unzureichend geklärtes Problem dar. Im Membranoxygenator entstehende thrombotische Ablagerungen bedingen dabei mitunter den Austausch des Oxygenators auf Grund einer eingeschränkten Gasaustauschkapazität. Die Konstruktion eines miniaturisierten ECMO-Modells soll eine genauere Aufschlüsselung der ablaufenden Gerinnungsprozesse an ECMO-Oxygenatorbestandteilen ermöglichen. Dazu erfolgte die Inbetriebnahme einer Pumpe mit in den Strömungskanal integrierten ECMO-Bestandteilen. Das betriebene Pumpenmodell wurde im Hinblick auf die angewandten Strömungseigenschaften und die Versuchskompatibilität untersucht. Unter Anwendung von Live-Cell-Imaging wurden an senkrecht in einer Flusskammer befindlichen Oxygenatorfasern Klotablagerungen aus bewegtem Blutplasma erzeugt. Fluoreszenzmikroskopische Analysen konnten keinen sicheren Nachweis von von-Willebrand-Faktor als Klotbestandteil erbringen. Die Klotbildung konnte trotz vorhandener Citratantikoagulation des Blutplasmas nachverfolgt werden. Die genaue Zusammensetzung des Klots bedarf weiterführender Untersuchungen
Versorgung polytraumatisierter Kinder und Jugendlicher im Universitätsklinikum Regensburg im Zeitraum 2007-2019
Get PDFZiel dieser Arbeit war es, Erkenntnisse über die Kinder und Jugendlichen mit Polytrauma, sowie deren Primärversorgung im Schockraum des Universitätsklinikums Regensburg zu erlangen. Dazu wurde eine retrospektive Datenanalyse von 184 Patienten durchgeführt, die im Rahmen einer klinikinternen, prospektiven Polytrauma-Studie im Zeitraum von 2007 bis 2019 erfasst worden sind. Im Rahmen dieser Studie waren Unfälle im Straßenverkehr die häufigste Ursache für das Polytrauma. Verletzungen des Kopfes waren bei den jüngsten Altersgruppen 0-5 und 6-10 Jahre signifikant häufiger als in den ältesten Altersgruppen. Die Inzidenz an Verletzungen des Abdomens und der Extremitäten nahm hingegen mit dem Alter zu. Ähnliche Ergebnisse zeigen sich auch in der aktuellen Literatur. Ein Polytrauma-CT wurde bei 88,0% unseres Kollektivs durchgeführt. Dabei wurde das CT mit steigendem Gruppenalter signifikant häufiger eingesetzt. Nach dem Konsens der aktuellen Literatur scheint der Einsatz des CT bei polytraumatisierten Patienten trotz kontroverser Diskussionen bezüglich der hohen Strahlenbelastung bei Kindern und Jugendlichen gerechtfertigt. Der Nutzen des CT überwiegt bei diesen Patienten deutlich, da durch eine schnelle und sensitive Diagnostik bestmöglich eine adäquate Therapie eingeleitet werden kann. Dies führt zu einer Minimierung der Traumafolgen und so zu einem besseren Überleben der Patienten
Sustainable polyphenolate assisted hydrotropic solubilization of riboflavin
Get PDFThe solubility of riboflavin is currently thoroughly investigated due to its importance for biological systems. Using real-life experiments and theoretical models, we study the hydrotropic performance and solubilizing mechanism of polyphenolic acid salts and derivatives for the solubilization of riboflavin.
Sodium/choline polyphenolates were both identified as potent hydrotropes for riboflavin via UV–Vis-spectroscopy. Using sodium ferulate and 3,4-dimethoxycinnamate, riboflavin’s water solubility can be increased 240 and >2000 times, respectively (molar polyphenolate/riboflavin ratios 6). Thus, polyphenolates were revealed as more efficient hydrotropes for riboflavin than the usually applied hydrotrope nicotinamide.
Solubilization, surface tension, and dynamic light scattering experiments ruled out the presence of larger well-defined aggregates around riboflavin. The (i) importance of the polyphenolates’ π-electron system for riboflavin’s solubilization, (ii) reversible bathochromic shifts of riboflavin’s absorbance by π-electron-rich solubilizers, (iii) mutual solubilization of riboflavin and of some aromatic sodium carboxylates, (iv) nuclear magnetic resonance (NMR) measurements, and (v) molecular dynamics confirmed π-complexation of riboflavin and aromatic carboxylates as reason for this hydrotropy. Additionally, NMR and NPT simulation indicated sodium polyphenolates to influence the ribityl chain. In water, the overall entropy of riboflavin dissolution is favorable, but in the presence of polyphenolate, the entropy of riboflavin’s dissolution is unfavorable and overcompensated by the respective enthalpy.
Finally, both methods hint to a minor influence of the ribityl chain on the dissolution process.
Moreover, real-life experiments and theoretical models state π-electron driven complex formation between the solute riboflavin and the hydrotropic polyphenolates
Weight Suppression, Binge Eating, and Purging as Predictors of Weight Gain During Inpatient Treatment in Persons With Bulimia Nervosa
Get PDFObjective
Persons with bulimia nervosa (BN) often gain weight during treatment, which potentially poses a threat to treatment adherence. Although weight suppression has been found to be a predictor of weight gain in persons with BN, research about the trajectory of weight changes during treatment and other predictors thereof is scarce.
Method
The current study examined weight suppression as well as self-reported binge eating severity and purging frequency at admission as predictors of weight change in 746 persons with BN (95% female) who received inpatient treatment at the Schoen Clinic Roseneck (Prien am Chiemsee, Germany) between 2015 and 2020.
Results
Body mass index (BMI) increased linearly across treatment weeks. Higher weight suppression predicted larger weight gain, particularly in those with a relatively low BMI at admission. More frequent purging and less severe binge eating predicted larger weight gain but high binge eating severity in combination with infrequent purging attenuated this effect.
Conclusions
Results replicate that those with high weight suppression are at higher risk for gaining weight during BN treatment but extend these findings in that this effect additionally depends on current BMI, similar to findings reported in persons with anorexia nervosa. They further demonstrate that the core features of BN—binge eating and purging—also predict weight change both separately and interactively and may, therefore, be considered in psychoeducation and therapy planning
"Tumor-Sink-Effekt bei bildbasierten Biomarkern in der initialen FDG-PET/CT beim aggressiven Non-Hodgkin-Lymphom: Ergebnisse aus der multizentrischen OPTIMAL>60-Studie"
Get PDFIn dieser Arbeit wurden die bildbasierten Biomarker von 670 FDG-PET/CT-Aufnahmen von Patienten mit aggressiven NHL aus der OPTIMAL>60-Studienpopulation ausgewertet. In diesem Rahmen wurde der Einfluss der FDG-Verteilungszeit, der Lymphomlast und der Stoffwechsellage auf die bildbasierten Biomarker des Blut-Pool, der Leber und der Lymphom-Manifestationen untersucht. Außerdem wurde auf Standort-Effekte in Bezug auf die bildbasierten Biomarker untersucht. Daneben wurden Standort-Unterschiede bezüglich der PET/CT-assoziierten Parameter Patientengewicht, Aktivitätsdosis und FDG-Verteilungszeit analysiert. Anhand des IPI-Risikogruppenvergleichs wurde orientierend auf einen prognostischen Wert der bildbasierten Biomarker getestet