Structure Dependent-Immunomodulation by Sugar Beet Arabinans via a SYK Tyrosine Kinase-Dependent Signaling Pathway

There is much interest in the immunomodulatory properties of dietary fibers but their activity may be influenced by contamination with microbial-associated molecular patterns (MAMPs) such as lipopolysaccharide (LPS) and lipoteichoic acids, which are difficult to remove completely from biological samples. Bone marrow-derived dendritic cells (BMDCs) from TLR2x4 double-KO mice were shown to be a reliable approach to analyse the immunomodulatory properties of a diverse range of dietary fibers, by avoiding immune cell activation due to contaminating MAMPs. Several of the 44 tested dietary fiber preparations induced cytokine responses in BMDCs from TLR2x4 double-KO mice. The particulate fractions of linear arabinan (LA) and branched arabinan (BA) from sugar beet pectin were shown to be strongly immune stimulatory with LA being more immune stimulatory than BA. Enzymatic debranching of BA increased its immune stimulatory activity, possibly due to increased particle formation by the alignment of debranched linear arabinan. Mechanistic studies showed that the immunostimulatory activity of LA and BA was independent of the Dectin-1 recognition but Syk kinase-dependent

Treatment characteristics and outcomes of pure Acinar cell carcinoma of the pancreas - A multicentric European study on radically resected patients

Background: Acinar cell carcinomas (ACC) belong to the exocrine pancreatic malignancies. Due to their rarity, there is no consensus regarding treatment strategies for resectable ACC. Methods: This is a retrospective multicentric study of radically resected pure pancreatic ACC. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Further endpoints were oncologic outcomes related to tumor stage and therapeutic protocols. Results: 59 patients (44 men) with a median age of 64 years were included. The median tumor size was 45.0 mm. 61.0% were pT3 (n = 36), nodal positivity rate was 37.3% (n = 22), and synchronous distant metastases were present in 10.1% of the patients (n = 6). 5-Years OS was 60.9% and median DFS 30 months. 24 out of 31 recurred systemically (n = 18 only systemic, n = 6 local and systemic). Regarding TNM-staging, only the N2-stage negatively influenced OS and DFS (p = 0.004, p = 0.001). Adjuvant treatment protocols (performed in 62.7%) did neither improve OS (p = 0.542) nor DFS (p = 0.159). In 9 cases, radical resection was achieved following neoadjuvant therapy. Discussion: Radical surgery is currently the mainstay for resectable ACC, even for limited metastatic disease. Novel (neo)adjuvant treatment strategies are needed, since current systemic therapies do not result in a clear survival benefit in the perioperative setting

Correlations between ERG, OCT, and Anatomical Findings in the rd10 Mouse

Background. To evaluate the correlation between ERG, OCT, and microscopic findings in the rd10 mouse. Methods. C57BL/6J wild type mice and rd10 mice were compared at the age of 2, 3, 5, 7, 9, 12, 24, and 48 weeks (each age group n=3) using full-field electroretinography (ERG), spectral domain Optical Coherence Tomography (sd-OCT), fluorescein angiography (FA), Hematoxylin & Eosin histology (HE), and immunohistology (IH). Results. While in wild type mice, the amplitude of a- and b-wave increased with light intensity and with the age of the animals, the rd10 mice showed extinction of the ERG beginning with the age of 5 weeks. In OCT recordings, the thickness of the retina decreased up to 9 weeks of age, mainly based on the degradation of the outer nuclear layer (ONL). Afterwards, the ONL was no longer visible in the OCT. HE staining and immunohistological findings confirmed the in vivo data. Conclusion. ERG and OCT are useful methods to evaluate the retinal function and structure in vivo. The retinal changes seen in the OCT closely match those observed in histological staining

Diese Region ist versorgt? - Messansätze zur Beurteilung der regionalen Versorgung mit hausärztlichen Angeboten auf dem Prüfstand

Wir betrachten die regionale Versorgungssituation mit Hausärzt:innen im Bundesland Brandenburg und nutzen dazu zwei unterschiedliche Messansätze. Zum einen betrachten wir in Anlehnung an die Versorgungsforschung zu anderen Bereichen der Daseinsvorsorge die Reisezeit zum bzw. zur nächsten Hausärzt:in und zum anderen nutzen wir einen angepassten Messansatz, der sich an der Methodik der Kassenärztlichen Vereinigungen orientiert, aber auf einer niedrigeren regionalen Aggregationsebene (auf der Gemeindeebene und nicht auf der Mittelbereichsebene) ansetzt. Wir betrachten hiernach die regionale Versorgungssituation für jeden Indikator separat und kombinieren schließlich beide Ansätze, um ein detaillierteres Bild zur Versorgungssituation zu erhalten und um den Aussagegehalt beider Messansätze zu überprüfen. Unser Ergebnis ist, dass eine Betrachtung der Versorgungssituation allein auf der Basis des Ansatzes der Kassenärztlichen Vereinigungen ein ungenaues Bild zeichnet. Der Mehrwert unseres Ansatzes liegt darin, eine kleinräumige Messung vorzunehmen, die z.B. sensitiver für Siedlungs- und auch Altersstrukturen ist. Ergebnis hiernach ist, dass nach unserer Methodik rd. 18% der Gemeinden bzw. 19% der Menschen des Landes Brandenburg unterversorgt wären. Zum Vergleich: Gemäß Ansatz der Kassenärztlichen Vereinigung Brandenburg wären hingegen nur rd. 8% der Gemeinden bzw. 1% der Menschen des Landes Brandenburg unterversorgt. Ein Ergebnis ist auch, dass sich die Bedeutung der Landärzt:innen für die Versorgung des ländlichen Raums eindrücklich zeigt, dass sich aber auch eine deutliche Unterversorgung in den höher verdichteten, verstädterten Räumen erkennen lässt. Hier stellt sich die Frage, ob die gemäß Zentrale Orte Prinzip eingeplante Mitversorgung des Umlandes überhaupt gewährleistet werden kann oder ob nicht vielmehr das Umland (und auch die Perpherie) bereits einen Mitversorgungsbeitrag für zentrale Orte übernimmt.We examine the regional supply situation with General Practitioners (Hausärzt:innen) in the federal state of Brandenburg using two different measurement approaches. First, we look at the travel time to the nearest general practitioner in accordance with research on other areas of public services, and second, we use an adapted measurement approach that is based on the methodology of the Association of Statutory Health Insurance Physicians (Kassenärztliche Vereinigungen), but at a lower regional aggregation level (at the municipal level and not at the level of the middle district). We then consider the regional supply situation for each indicator separately and eventually combine both approaches to obtain a more detailed picture of the supply situation and to verify the informative value of both measurement approaches. Our result is that an analysis of the health care situation based solely on the approach of the ASHIP-accredited physicians' associations paints an inaccurate picture. The added value of our approach consists in taking a small-scale measurement, which is more sensitive, for example, to settlement and age structures. The result is that, according to our methodology, about 18% of the communities or 19% of the people in the state of Brandenburg would be underserved. For comparison: According to the approach of the Association of Statutory Health Insurance Physicians Brandenburg, only about 8% of the communities or 1% of the people of Brandenburg would be underserved. Another result is that the importance of rural physicians for the supply of rural areas is clearly demonstrated, but that there is also a noticeable undersupply in the more densely populated, urbanized areas. This raises the question of whether the planned supply of the surrounding area in accordance with the central places principle can be guaranteed at all, or whether the surrounding area (and also the periphery) is not already making a contribution to the supply of the cities

"Wir spürten den Herzschlag brüderlicher Liebe" - vom transnationalen Austausch der Herrnhuter Brüdergemeine im Kalten Krieg

Richter H. "Wir spürten den Herzschlag brüderlicher Liebe" - vom transnationalen Austausch der Herrnhuter Brüdergemeine im Kalten Krieg. In: Uta B, Christiane R, eds. "Umworbener Klassenfeind" - das Verhältnis der DDR zu den USA. Ch. Links: Berlin; 2006: 96-122

Cellulase and Alkaline Treatment Improve Intestinal Microbial Degradation of Recalcitrant Fibers of Rapeseed Meal in Pigs

The aim of the current study was to investigate whether degradation of rapeseed meal (RSM) by a swine gut microbiota consortium was improved by modifying RSM by treatment with cellulase (CELL), two pectinases (PECT), or alkaline (ALK) compared to untreated RSM and to assess whether microbiota composition and activity changed. The predicted relative abundances of carbohydrate digestion and absorption, glycolysis, pentose phosphate pathway, and pyruvate metabolism were significantly increased upon CELL and ALK feeding, and CELL and ALK also exhibited increased total short-chain fatty acid (SCFA) production compared to CON. Megasphaera, Prevotella, and Desulfovibrio were significantly positively correlated with SCFA production. Findings were validated in ileal cannulated pigs, which showed that CELL and ALK increased fiber degradation of RSM. In conclusion, CELL and ALK rather than PECT1 or PECT2 increased fiber degradation in RSM, and this information could guide feed additive strategies to improve efficiency and productivity in the swine industry

Descemet Membrane Endothelial Keratoplasty (DMEK) - Made in Halle

Background:To characterize the effects of intravitreal injections of iodoacetic acid (IAA) in comparison to its systemic application as a measure to induce unilateral photoreceptor degeneration.Methods:Seven-week-old C57BL/6 J mice received either intravitreal injections of IAA or systemic treatment (intraperitoneal vs intravenous) and were observed in the following 5 weeks using ERG, OCT, and histology.Results:Systemic treatment with IAA induced high toxic effects and a high mortality in contrast to the intravitreal injection. Intraperitoneal application had no effect on the retina. Intravenous application of 2 × 30 mg/kg BW IAA (time between injections 3.5 h) resulted in an extinction of the ERG and a thinning of the retina, in particular of the outer nuclear layer (ONL) indicating photoreceptor degeneration. Animals receiving intravitreal injections developed cataracts already at low concentrations (up to 100 % at 0.25 mg/kg BW). Higher intravitreal IAA doses led to extinguished ERGs. In histology, a thinning of the entire retina was observed that was most prominent in the inner part of the retina.Conclusions:In contrast to intraperitoneal administration, intravenous application of IAA led to a selective photoreceptor degeneration. After intravitreal injection, dense cataracts were already observed at concentrations lower than those needed to induce changes in the ERG. ERG results must be interpreted carefully. A thinning of all retinal layers rather than a specific outer retinal degeneration was observed upon intravitreal injection. IAA is not a useful model to induce outer retinal degeneration in mice

Synbiotic matchmaking in Lactobacillus plantarum: Substrate screening and gene-trait matching to characterize strain-specific carbohydrate utilization

Synbiotics are food supplements that combine probiotics and prebiotics to synergistically elicit a health effect in humans. Lactobacillus plantarum exhibits remarkable genetic and phenotypic diversity, in particular in strain-specific carbohydrate utilization capacities, and several strains are marketed as probiotics. We have screened 77 L. plantarum strains for their abilities to utilize specific prebiotic fibers, revealing variable and strain-specific growth efficiencies on isomalto-and galactooligosaccharides. We identified a single strain within the screening panel that was able to effectively utilize inulin and fructooligosaccharides (FOS), which did not support efficient growth of the rest of the strains. In the panel we tested, we did not find strains that could utilize arabinoxylooligosaccharides or sulfated fucoidan. The strainspecific growth phenotype on isomaltooligosaccharides was further analyzed using high-performance anion-exchange chromatography, which revealed distinct substrate utilization phenotypes within the strain panel. The strain-specific phenotypes could be linked to the strains' genotypes by identifying gene clusters coding for carbohydrate membrane transport systems that are predicted to be involved in the utilization of isomaltose and other (unidentified) oligosaccharides in the isomaltooligosaccharide substrate.</p

Dietary calcium phosphate strongly impacts gut microbiome changes elicited by inulin and galacto-oligosaccharides consumption

Background: Fructo-oligosaccharides (FOS), inulin, and galacto-oligosaccharides (GOS) are widely recognized prebiotics that profoundly affect the intestinal microbiota, including stimulation of bifidobacteria and lactobacilli, and are reported to elicit several health benefits. The combination of dietary FOS and inulin with calcium phosphate was reported to stimulate commensal Lactobacillus populations and protect the host against pathogenic Enterobacteriaceae, but little is known about the effects of GOS in diets with a different level of calcium phosphate. Methods: We investigated the microbiome changes elicited by dietary supplementation with GOS or inulin using diets with high (100 mmol/kg) and low (30 mmol/kg) calcium phosphate levels in adult Wistar rats. Rats were acclimatized to the respective experimental diets for 14 days, after which fecal material was collected, DNA was extracted from fecal material, and the V3‑V4 region of the bacterial 16S rRNA gene was amplified with PCR, followed by microbial composition analysis. In tandem, the organic acid profiles of the fecal material were analyzed. Results: Feeding rats non-supplemented (no prebiotic-added) diets revealed that diets rich in calcium phosphate favored members of the Firmicutes and increased fecal lactic, succinic, acetic, propionic, and butyric acid levels. In contrast, relatively low dietary calcium phosphate levels promoted the abundance of mucin degrading genera like Akkermansia and Bacteroides, and resulted in increased fecal propionic acid levels and modest increases in lactic and butyric acid levels. Irrespective of the calcium phosphate levels, supplementation with GOS or inulin strongly stimulated Bifidobacterium, while only high calcium phosphate diets increased the endogenous Faecalibaculum populations. Conclusions: Despite the prebiotic’s substantial difference in chemical structure, sugar composition, oligomer size, and the microbial degradation pathway involved in their utilization, inulin and GOS modulated the gut microbiota very similarly, in a manner that strongly depended on the dietary calcium phosphate level. Therefore, our study implies that the collection of detailed diet information including micronutrient balance is necessary to correctly assess diet-driven microbiota analysis. [MediaObject not available: see fulltext.