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Psychological well-being as a motive for and result of post-bariatric body contouring procedures
No full textObjective: This study investigates whether psychological well-being in post-bariatric patients seeking body contouring procedures differs from those who do not seek body contouring procedures, those who have already undergone body contouring procedures, and those who are unsure about body contouring procedures. Methods: An anonymous, nonrandomized, cross-sectional survey study was designed. Psychological well-being of four groups of post-bariatric-patients (undergone body contouring procedures, seeking body contouring procedures, not seeking body contouring procedures, unsure about body contouring procedures) were compared. Results: A total of 345 patients were included in this study. No significant difference between patients seeking body contouring procedures and those not seeking body contouring procedures was found with regard to depressive symptoms, self-esteem, and body image. Patients who had already undergone body contouring procedures scored lower on depressive symptoms (p = 0.035) and reported feeling more attractive (p < 0.001) and less insecure (p = 0.030) than patients who had not yet undergone body contouring procedures but sought it. Satisfaction with the result of the body contouring procedures was associated with lower depression levels (p < 0.001), higher self-esteem (p < 0.001) and a more positive body-image (p < 0.001). Conclusions: Depressive symptoms or low self-esteem are not motivational factors for post-bariatric patients to seek body contouring procedures. Body contouring procedures are associated with improvement in psychological well-being in post-bariatric patients. Patients' satisfaction with the result of the body contouring procedures is significantly associated with positive psychological well-being
RalGAP complexes control secretion and primary cilia in pancreatic disease
No full textκB-Ras/RalGAP complexes limit the activity of Ral GTPases, which function in EGFR/Ras signaling. RalGAP expression is down-regulated in pancreatic cancer; however, the role of RalGAP and Ral GTPases in tumor development in vivo remained unclear. Here, we show that pancreatic RalGAPβ deficiency alone is sufficient to induce inflammation and neoplasia in vivo. We identify that this phenotype is triggered by disturbance of the secretory pathway and polarized exocytosis in acinar cells, demonstrating that RalGAP complexes uphold spatial control of Ral activity. We furthermore show that RALGAPβ deficiency results in defective primary cilium assembly, a process required for efficient acinar regeneration upon inflammation. Only primary cilium formation depends on κB-Ras proteins, suggesting that κB-Ras proteins are not essential for all RalGAP complex-controlled processes. In combination with an oncogenic KRASG12D mutation, RalGAPβ deficiency leads to a dramatic shortening of tumor latency and median survival. Our results highlight an important role of RalGAP/Ral signaling in upholding acinar cell identity and preventing pancreatic cancer development
Single-Cell Transcriptomics Identifies a Prominent Role for the MIF-CD74 Axis in Myasthenia Gravis Thymus
No full textBackground and Objectives: Myasthenia gravis (MG) is an autoimmune disease most frequently caused by autoantibodies (auto-Abs) against the acetylcholine receptor (AChR) located at the neuromuscular junction. Thymic follicular hyperplasia is present in most of the patients with early-onset AChR-Ab+ MG (EOMG), but its cellular and molecular drivers and development remain poorly understood. Methods: We constructed a single cell-based transcriptional profile of lymphoid cell types in thymi from 11 immunotherapy-naïve patients with EOMG. Multiplex histology and ELISA were used to determine migration inhibitory factor (MIF) levels. Results: Within EOMG thymi, we consistently observed 6 distinct clusters of B-cell populations maturing toward germinal center (GC)–associated and Ab-secreting cells, featuring prominent GC activity, as indicated by substantial clonal expansions and cycling B-cell subsets. Cell-cell interactome predictions identified strong interactions between T cells and GC-associated and memory B cells, dominated by B-cell prosurvival signaling through the MIF-CD74 axis. Multiplex histology confirmed abundant expression of CD74 in MG thymic B cells. Circulating MIF levels in EOMG correlated with higher disease severity as assessed by Myasthenia Gravis Foundation of America status. Discussion: Our data not only illustrate and define hyperplastic thymic niches in MG as favorable environments for pathogenic B-cell proliferation, maturation, and persistence but also suggest that the MIF-CD74 axis should be investigated for potential novel therapeutic targeting in EOMG
Spinal GABA transporter 1 contributes to evoked-pain related behavior but not resting pain after incision injury
No full textThe inhibitory function of GABA at the spinal level and its central modulation in the brain are essential for pain perception. However, in post-surgical pain, the exact mechanism and modes of action of GABAergic transmission have been poorly studied. This work aimed to investigate GABA synthesis and uptake in the incisional pain model in a time-dependent manner. Here, we combined assays for mechanical and heat stimuli-induced withdrawal reflexes with video-based assessments and assays for non-evoked (NEP, guarding of affected hind paw) and movement-evoked (MEP, gait pattern) pain-related behaviors in a plantar incision model in male rats to phenotype the effects of the inhibition of the GABA transporter (GAT-1), using a specific antagonist (NO711). Further, we determined the expression profile of spinal dorsal horn GAT-1 and glutamate decarboxylase 65/67 (GAD65/67) by protein expression analyses at four time points post-incision. Four hours after incision, we detected an evoked pain phenotype (mechanical, heat and movement), which transiently ameliorated dose-dependently following spinal inhibition of GAT-1. However, the NEP-phenotype was not affected. Four hours after incision, GAT-1 expression was significantly increased, whereas GAD67 expression was significantly reduced. Our data suggest that GAT-1 plays a role in balancing spinal GABAergic signaling in the spinal dorsal horn shortly after incision, resulting in the evoked pain phenotype. Increased GAT-1 expression leads to increased GABA uptake from the synaptic cleft and reduces tonic GABAergic inhibition at the post-synapse. Inhibition of GAT-1 transiently reversed this imbalance and ameliorated the evoked pain phenotype
Synthese und Spektroskopie Eu 3+ aktivierter Metallate und Phosphate für die Hochenergieanregung
No full textDiese Arbeit widmet sich der Optimierung und Charakterisierung neuer Eu3+ substituierter Molybdate, Wolframate und Phosphate zur Anwendung unter Hochenergieanregung im Vakuum-UV- oder Röntgenbereich. Ziel war es, geeignete Wirtsverbindungen für den Einsatz in strahlenresistenten Leuchtstoffen, Szintillatoren und bildgebenden Verfahren zu identifizieren. Die untersuchten Verbindungen zeigten deutliche Unterschiede im Emissionsverhalten in Abhängigkeit von Struktur, Zusammensetzung und Anregungsenergie. Besonders das Mo-haltige La2Hf3(MoO4)9 erwies sich unter Röntgenanregung als sehr effizienter Emitter, während das entsprechende Wolframat unter VUV-Anregung überlegen war. Weitere untersuchte Verbindungen wie La2Mo2O2 sowie Li3Ba3La3(MoO4)8 und Li3Ba3La3(WO4)8 zeigten ebenfalls robuste, konzentrationstolerante Emission. Unter den Phosphaten stach neben dem β-Ca2P2O7 vor allem Ca9Y(PO4)7 hervor, dessen effiziente Emission im Bereich des biologischen Fensters es für biomedizinische Bildgebung besonders prädestiniert. Die Ergebnisse bieten neue Einblicke in die Struktur-Lumineszenz-Korrelation unter Hochenergieanregung und liefern eine fundierte Basis für die Suche und Optimierung anwendungsnaher Lumineszenzmaterialien.This work focuses on the development and characterization of novel Eu3+ substituted molybdates, tungstates, and phosphates for applications under high-energy excitation in the vacuum-UV and X-ray range. The aim was to identify suitable host materials for use in radiation-resistant phosphors, scintillators, and imaging systems. The investigated compounds exhibited significant differences in their emission behavior depending on structure, composition, and excitation energy. In particular, Mo-containing La2Hf3(MoO4)9 demonstrated efficient emission under X-ray excitation, while the corresponding tungstate proved superior under VUV excitation. Additional compounds such as La2Mo2O2 as well as Li3Ba3La3(MoO4)8 and Li3Ba3La3(WO4)8 also showed robust, concentration-tolerant emission. Among the phosphates, β-Ca2P2O7 and especially Ca9Y(PO4)7 stood out due to their intense emission in the biological window, making them promising candidates for biomedical imaging. The results provide new insights into structure - luminescence correlations under high-energy excitation and offer a solid foundation for the search and optimization of application-oriented luminescent materials
Telemedizin in der Augenheilkunde: Erfahrungen und Erwartungen deutscher Ophthalmologen im ambulanten und stationären Sektor
No full textMit zunehmender Verbreitung digitaler Technologien hat sich das Spektrum von Telemedizin in
der Augenheilkunde erweitert. Es umfasst unter anderem die Befundung, Überwachung und
postoperative Betreuung von Patienten. Diese Arbeit gibt einen Einblick in die Nutzung von
Telemedizin in der Augenheilkunde in Deutschland und betrachtet fachspezifische Nutzen,
Hürden, Erfahrungen bezüglich ihrer Verwendung sowie Veränderungen im Rahmen der Covid-
19-Pandemie.
Die durchgeführte Umfrage enthält 57 Fragen, unterteilt in sechs Blöcke, abgestimmt auf die
Tätigkeitsbereiche der Teilnehmer. Die Befragung wurde als Online-Umfrage unter 528
ambulanten und 166 stationären augenärztlichen Einrichtungen in Deutschland vom 15.12.2023
bis zum 30.01.2024 durchgeführt. Insgesamt wurden 190 gültige Teilnahmen an der Umfrage
erhalten. Die Ergebnisse zeigen, dass Telemedizin in der Augenheilkunde nicht flächendeckend
verbreitet ist. Primäre Hürden sind Diagnosesicherheit, Datenschutz, gesetzliche Restriktionen,
Finanzierungsrisiken und technische Ausstattung. Die Tätigkeit im stationären Sektor, größeren
Einrichtungen sowie operative Tätigkeit erhöhen die Nutzungswahrscheinlichkeit von
Telemedizin signifikant. Hauptgrund für die Nutzung ist die potentielle Einsparung zeitlicher
Ressourcen. Die Bedeutung von Telemedizin hat durch die Covid-19-Pandemie für die Hälfte der
Befragten nicht zugenommen. Es lässt sich zudem nicht bestätigen, dass durch die Covid-19-
Pandemie die Nachfrage von Telemedizin in der Augenheilkunde signifikant gestiegen ist. Die
Hälfte der Befragten empfindet Telemedizin als zusätzliche Belastung im Alltag, eine Mehrheit
bevorzugt weiterhin den physischen Arztkontakt. Die physische Untersuchung bleibt daher auch
in Zukunft essentiell
The Baum–Connes conjecture for extensions
No full textThis note provides a counterexample showing that the assumptions that Chabert and Echterhoff have imposed in their permanence property of the Baum–Connes conjecture for group extensions cannot be simplified
Therapeutisches Drug Monitoring von Psychopharmaka bei Patienten mit erhöhtem Delir-Risiko zur Verbesserung des klinischen Delir-Managements
No full textÄltere Patienten mit Delir weisen eine hohe Mortalität und eine veränderte Pharmakokinetik von Psychopharmaka auf. Ziel dieser Arbeit war es, durch Therapeutisches Drug Monitoring (TDM) und populationsbasierte Pharmakokinetik-Modelle die Arzneimitteltherapiesicherheit zu verbessern. In fünf Gruppen wurden Kapillarblutkonzentrationen von Pipamperon, Melperon, Risperidon, Mirtazapin und Citalopram bei 71 älteren Patienten untersucht. Die Modelle zeigten interindividuelle Variabilität in Clearance, Verteilungsvolumen und Halbwertszeiten, die von Literaturwerten jüngerer Erwachsener abwichen. Mess- und Dokumentationsfehler, eingeschränkte Organfunktionen und Werte unterhalb der Bestimmungsgrenze stellten Limitationen dar. Die Kapillarblutabnahme mittels der VAMSTM-Methode ermöglichte den qualitativen Nachweis aller Substanzen. Die Ergebnisse betonen die Relevanz von TDM und individualisierten Dosierungen für ältere Delir-Patienten sowie den Bedarf größerer klinischer Studien.Older patients with delirium exhibit high mortality and altered pharmacokinetics of psychotropic drugs. This study aimed to enhance medication safety through therapeutic drug monitoring (TDM) and population pharmacokinetic modeling. Capillary blood concentrations of pipamperone, melperone, risperidone, mirtazapine, and citalopram were analyzed in 71 elderly patients across five groups. The models revealed substantial interindividual variability in clearance, volume of distribution, and half-lives, deviating from values reported in younger adults. Limitations included measurement and documentation inaccuracies, impaired organ function and concentrations below the limit of quantification. Capillary blood sampling using the VAMSTM method enabled reliable qualitative detection of all compounds. The findings support the relevance of TDM and individualized dosing in elderly delirium patients and highlight the need for larger clinical studies
Thioredoxins m regulate plastid glucose-6-phosphate dehydrogenase activity in Arabidopsis roots under salt stress
No full textPlants contain several NADPH-producing enzymes including glucose-6-phosphate dehydrogenases (G6PDH) with different sub-cellular localizations. The activity of plastidial G6PDHs is redox-regulated by thioredoxins (TRX). Although specific TRXs are known to regulate chloroplastic isoforms of G6PDH, little information is available for plastidic isoforms found in heterotrophic organs or tissues. Here, we investigated TRX regulation of the two G6PDH plastidic isoforms of Arabidopsis roots during exposure to a mild salt stress. We report that 'in vitro' m-type TRXs are the most efficient regulators of the G6PDH2 and G6PDH3 mainly found in Arabidopsis roots. While expression of the corresponding 'G6PD' and plastidic 'TRX' genes was marginally affected by salt, it impaired root growth of several of the corresponding mutant lines. Using an 'in situ' assay for G6PDH, G6PDH2 was found to be the major contributor to salt-induced increases in activity, while data from ROS assays further provide 'in vivo' evidence that TRX m acts in redox regulation during salt stress. Taken together, our data suggest that regulation of plastid G6PDH activity by TRX m may be an important player regulating NADPH production in Arabidopsis roots undergoing salt stress
Transcriptomic analysis of Chinese yam (Dioscorea polystachya Turcz.) variants indicates brassinosteroid involvement in tuber development
No full text'Dioscorea' is an important but underutilized genus of flowering plants that grows predominantly in tropical and subtropical regions. Several species, known as yam, develop large underground tubers and aerial bulbils that are used as food. The Chinese yam ('D. polystachya' Turcz.) is one of the few 'Dioscorea' species that grows well in temperate regions and has been proposed as a climate-resilient crop to enhance food security in Europe. However, the fragile, club-like tubers are unsuitable for mechanical harvesting, which is facilitated by shorter and thicker storage organs. Brassinosteroids (BRs) play a key role in plant cell division, cell elongation and proliferation, as well as in the gravitropic response. We collected RNA-Seq data from the head, middle and tip of two tuber shape variants: F60 (long, thin) and F2000 (short, thick). Comparative transcriptome analysis of F60 vs. F2000 revealed 30,229 differentially expressed genes (DEGs), 1,393 of which were differentially expressed in the growing tip. Several DEGs are involved in steroid/BR biosynthesis or signaling, or may be regulated by BRs. The quantification of endogenous BRs revealed higher levels of castasterone (CS), 28-norCS, 28-homoCS and brassinolide in F2000 compared to F60 tubers. The highest BR levels were detected in the growing tip, and CS was the most abundant (439.6 ± 196.41 pmol/g in F2000 and 365.6 ± 112.78 pmol/g in F60). Exogenous 24-epi-brassinolide (epi-BL) treatment (20 nM) in an aeroponic system significantly increased the width-to-length ratio (0.045 ± 0.002) compared to the mock-treated plants (0.03 ± 0.002) after 7 weeks, indicating that exogenous epi-BL produces shorter and thicker tubers. In this study we demonstrate the role of BRs in 'D. polystachya' tuber shape, providing insight into the role of plant hormones in yam storage organ development. We found that BRs can influence tuber shape in Chinese yam by regulating the expression of genes involved cell expansion. Our data can help to improve the efficiency of Chinese yam cultivation, which could provide an alternative food source and thus contribute to future food security in Europe