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Access to a newly adapted diabetes-specific multimodal cross-sectoral and interdisciplinary psychotherapeutic care option for a high-risk group of patients with diabetes mellitus and distress : protocol for the minDBe pilot study
(2025) Zara, Sandra; Kruse, Johannes; Kampling, Hanna
Background: Diabetes is a chronic disease requiring daily self-management to regulate physiological parameters like glycemic control. Despite extensive training being available, most patients with diabetes do not meet their target blood sugar levels. Moreover, diabetes-related emotional distress and psychological burden in the form of depressive and anxiety symptoms are very common. Patients with these challenges represent a high-risk group in terms of increased morbidity, mortality, and health care costs as well as decreased quality of life. Hence, in addition to somatically focused standard care, this patient group requires specific treatment options that also address psychosocial aspects. However, these treatments are often not available in routine care. Psychosomatic outpatient clinics (PsIAs) could address this gap by offering multimodal and integrative treatment. However, the indication for treatment in PsIAs and the referral pathways for patients with diabetes from practices or diabetes clinics to PsIAs remain complicated. Moreover, specific treatment options must be adapted. Objective: This study aims to assess the needs for referral pathways to PsIAs from the patient and service provider perspectives and to adapt the already effective psychosomatic intervention psy-PAD for a group setting (psy-PADGroup), fitting the multimodal PsIA structures. Methods: This pilot study comprises an explorative qualitative design based on a multilevel approach, using 2 work packages: work package 1 assesses the patient perspective (n=40) using focus groups, as well as the service provider perspective with interviews (n=30). Work package 2 comprises an expert workshop with clinicians and patient representatives (n=10) to adapt the psy-PADGroup manual for the modalities of PsIAs. We will audio-record the patient focus groups and service provider interviews. The audio recordings will be transcribed and analyzed using content analysis within the framework of interpretative text evaluations with MAXQDA. Results: Outcomes will be (1) the needs regarding referral pathways, (2) short questionnaires to economically assess the acceptance and feasibility of the referral pathways in preparation for the minDBe main study, and (3) the adapted psy-PADGroup intervention for an interdisciplinary multimodal treatment option to be implemented in the structures of PsIAs. Conclusions: The minDBe pilot study will lay the foundation for the minDBe main study, which aims to evaluate the psy-PADGroup as part of an interdisciplinary multimodal psychotherapeutic treatment program in a randomized controlled trial.
Airway basal stem cells are necessary for the maintenance of functional intraepithelial airway macrophages
(2025) Kooistra, Tristan; Saez, Borja; Roche, Marly; Egea-Zorrilla, Alejandro; Li, Dongzhu; Anketell, Dilanjan; Nguyen, Nhan; Villoria, Jorge; Gillis, Jacob; Petri, Eva; Vera, Laura; Blasco-Iturri, Zuriñe; Smith, Neal P.; Alladina, Jehan; Zhang, Yanting; Vinarsky, Vladimir; Shivaraju, Manjunatha; Sheng, Susan L.; Chen, Michelle; Gonzalez-Celeiro, Meryem; Mou, Hongmei; Waghray, Avinash; Lin, Brian; Paksa, Azadeh; Yanger, Kilangsungla; Tata, Purushotama Rao; Zhao, Rui; Causton, Benjamin; Zulueta, Javier J.; Prosper, Felipe; Cho, Josalyn L.; Villani, Alexandra-Chloe; Haber, Adam; Rajagopal, Jayaraj; Medoff, Benjamin D.; Pardo-Saganta, Ana
Stem cells are known to provide signals that contribute to the maintenance and function of neighboring cells. We demonstrate that Notch signaling arising from airway basal stem cells is necessary for the function of a unique population of intraepithelial airway macrophages (IAMs) in the murine trachea. Without this stem cell signaling, IAMs lose MHC II expression, which in turn prevents antigen-induced allergic inflammation. Distal murine airways do not harbor basal stem cells, and, in this region of the lung, allergic inflammation proceeds unperturbed. We speculate that the functional coupling of specific anatomically restricted stem cell populations and adjacent immune cells is one mechanism for ensuring that inflammatory responses are compartmentalized to regions of injury. Basal stem cells are found throughout the human airway tree and we demonstrate the existence of human IAM-like cells, suggesting that their interaction may influence airways disease.
Umami enhancing properties of enzymatically hydrolyzed mycelium of flammulina velutipes cultured on potato pulp
(2025) Happel, Katharina; Zeller, Lea; Hammer, Andreas Klaus; Zorn, Holger
The aim of this study was to hydrolyze cultivated fungal mycelium and to evaluate the effect on its taste. Potato pulp, a by-product of the potato starch industry, was therefore successfully utilized as a substrate for submerged cultivation of Flammulina velutipes, yielding a product with an estimated fungal content of 83% ± 3%. The fermentation increased the protein content from 5.3 ± 0.4 g/100 g DM to 13.9 ± 0.1 g/100 g DM with a biological protein value of 86. The fermentate was enzymatically hydrolyzed by Corolase APC-peptidase. After optimization of the hydrolysis conditions, a degree of hydrolysis (DH) of 75.1% ± 1.0% was achieved. The protein hydrolysis increased the contents of free glutamate more than 20-fold from 8.7 ± 0.1 mg/L to 188.7 ± 1.2 mg/L. Elevated glutamate levels led to an umami taste perception in aqueous solution and taste-enhancing properties in vegetable broth. Noteworthy, the fermentate itself exhibited an intrinsic peptidase activity. Without addition of auxiliary peptidases, mycelial enzymes caused a DH of 33.9% ± 0.7% and a free glutamate content of 99.1 ± 0.7 mg/L. For these samples, an increase in umami taste was only observed in vegetable broth, but not in water, indicating taste-enhancing properties but low umami taste. In addition to the nutritional and health benefits of fungi, their hydrolysates are of great interest for use as a protein booster with flavor-enhancing properties.
Targeting transglutaminase 2 : pathways to celiac disease therapies
(2025) Endrizzi, Alexandra; Grunst, Pauline; Rudloff, Silvia; De Laffolie, Jan; Zimmer, Klaus-Peter; Stricker, Sebastian
Background: Transglutaminase 2 (TG2)-mediated enzymatic modification of gliadin peptides plays a major role in the pathogenesis of celiac disease (CD). Different inhibitory mechanisms have been reported to reduce TG2 activity but comparative data on the cellular level are lacking. Furthermore, recent evidence suggested that endogenous redox proteins such as endoplasmic reticulum resident protein 57 (ERp57, inhibits TG2) and thioredoxin-1 (TRX, activates TG2) may regulate TG2 activity. In this study, we aimed to compare the effects and applicability of different inhibitors on the activity of recombinant and cellular TG2. Furthermore, we investigated the role of ERp57 and TRX in the context of CD by using siRNA-mediated knockdown in Caco-2 cells. Methods: The effect of TG2 inhibitors on recombinant and extracellular TG2 activity was investigated by using photometric and fluorometric quantitation of the cross-linking of biotinylated gliadin peptide P56-88 or 5-(biotinamido)-pentylamine. After siRNA knock-down, the protein levels of ERp57, TRX, and TG2 as well as TG2 activity were investigated by using Western blotting and fluorometry in Caco-2 cells. Results: The active-site-directed inhibitors ERW1041, KCC009, and cysteamine as well as the allosteric inhibitor LDN27219 revealed the most prominent reduction in recombinant and cellular (35%–50%) TG2 activity. In contrast, PX12, S-Nitroso-N-acetyl-DL-penicillamine, zinc chloride, and ascorbic acid either did not affect TG2 activity or had only moderate effects at high doses close to cytotoxic concentrations. SiRNA knockdown of TG2 resulted in a prominent reduction (63%) in TG2 activity, whereas knockdown of ERp57 did not; knockdown of TRX only slightly (27%) reduced TG2 activity. Conclusion: Active-site-directed inhibitors, LDN27219 and knockdown of TG2 expression significantly reduced extracellular TG2 activity and represent potential alternative treatment targets in the context of CD
Soluble urokinase plasminogen activator receptor (suPAR) plasma concentration is reduced using minimized extracorporeal circulation : results of a secondary analysis of a prospective observational study
(2025) Zajonz, Thomas S.; Edinger, Fabian; Götze, Juliane; Markmann, Melanie; Sander, Michael; Koch, Christian; Schneck, Emmanuel
Background: Minimized extracorporeal circulation (miECC) was developed to mitigate the adverse effects of cardiopulmonary bypass (CPB), yet its impact on soluble Urokinase plasminogen activator receptor (suPAR) is unclear. SuPAR has been linked to adverse outcomes, including acute kidney injury (AKI). This study investigated perioperative suPAR kinetics in patients undergoing cardiac surgery with miECC or conventional CPB (cCPB) and explored its association with AKI, postoperative delirium (POD), and infections. Methods: This study is a secondary analysis of an observational cohort of 79 cardiac surgical patients. It evaluates perioperative suPAR levels and their association with the type of CPB used (miECC vs. cCPB) and postoperative adverse outcomes, including POD, AKI, and infections. Statistical analyses included repeated measures ANOVA, Wilcoxon tests, logistic regression, and ROC curve analysis to assess the predictive value of suPAR for these outcomes. Results: During surgery, suPAR significantly increased to higher Levels with the use of cCPB compared to miECC (p = 0.027; odds ratio of 0.69 [0.57–0.84], p < 0.001). The use of miECC was an independent influencing factor on suPAR (−0.41 ± 0.1; p < 0.001). Regardless of the type of CPB, suPAR levels differed significantly between patients with and without kidney damage (n = 25; no AKI: 1.6 [1.1–2.0], AKI: 1.7 [1.3–2.4], p < 0.001). Multivariate regression analysis showed that AKI was an independent influencing factor on suPAR (−0.49 ± 0.1; p < 0.001). SuPAR demonstrated only low predictive value for AKI and could not predict POD. Conclusions: This study provides evidence that miECC is associated with lower intraoperative suPAR levels, suggesting a reduced inflammatory response compared to cCPB. While suPAR levels were significantly higher in patients with AKI, their predictive value for AKI remains limited. Furthermore, suPAR did not predict POD but was elevated in patients with pneumonia.