Previous studies have demonstrated that expression of either constitutively‐active (CA) or dominant negative (DN) RhoA reduced tight junction barrier function in cultured MDCK monolayers (Jou et al. 1998). However, the mechanisms by which RhoA disruption causes barrier loss have not been defined. The aims of this study were to determine whether RhoA regulates barrier function in mammary epithelia and to identify the molecular events responsible. V14 and N19 (CA and DN, respectively) RhoA were expressed in EpH4 mammary epithelial cells. RhoA (CA or DN) expression in confluent monolayers caused a dose‐dependent loss of transepithelial electrical resistance. Neither trafficking of ZO‐1 and occludin to the tight junction nor cell viability were affected by CA or DN RhoA expression, but western blots showed that ERK and Akt were phosphorylated (consistent with activation) after either CA or DN RhoA expression. Transcript content of several claudins was altered after CA or DN RhoA expression. Most notably, claudin‐2 mRNA and protein expression were increased following either CA or DN RhoA expression. These data demonstrate that RhoA regulates the barrier in mammary epithelia and suggest that increased claudin‐2 expression contributes to RhoA‐mediated tight junction regulation. Supported by Charite Universitaetsmedizin Berlin.
Abstract The impact of ustekinumab (UST) on mucosal- and fistula healing and extraintestinal manifestations (EIM) in Crohn’s disease (CD) were not fully elucidated in the registration trials. In this prospective, multicenter study (EudraCT number: 2017-005151-83) we evaluated the German label real-world-effectiveness of UST to achieve the primary endpoint of combined clinical and endoscopic response at week 52 and several secondary endpoints. Of 79 screened we enrolled 52 patients (female n = 28, bionaïve n = 13, biologic n = 39). At week 52 (per protocol analysis), 52% (n = 13/25) of patients achieved the primary endpoint [50% (n = 3/6) in the bionaïve, 45.5% (n = 5/11) biologic, 62.5% (n = 5/8 ) multiple biologics cohorts, respectively with age as independent predictor [OR 95% CI 0.933 (0.873, 0.998) p = 0.043], 60% (n = 15/25) achieved endoscopic response [50% (n = 3/6) in the bionaïve, 54.5% (n = 6/11) biologic, 75% (n = 6/8) multiple biologics cohorts, respectively], 36% (n = 9/25) achieved endoscopic remission [50% (n = 3/6) in the bionaïve, 27.3% (n = 3/11) biologic, 37.5% (n = 3/8) multiple biologics cohorts, respectively], 48% (n = 12/25) achieved mucosal healing [50% (n = 3/6) in the bionaïve, 36.4% (n = 4/11) biologic, 62.5% (n = 5/8) multiple biologics cohorts, respectively]. All achieved a fistula response and 33.3% (n = 1/3) in the multiple biologics group fistula remission at week 52. EIM decreased (week 0 28.2% vs. week 52 8%). CRP, FCP, PRO-2, EQ-5D-5L improved throughout. 36 patients (69.2%) experienced ≥ 1 treatment emergent adverse event, in 8 (15.4%) cases rated as severe and in 5 (9.6%) leading to UST discontinuation, but no very severe events or deaths. The effectiveness of UST was better than in the registration trials.
Abstract Winterweide auf Niedermoor wurde in der Literatur bisher ungünstig bewertet. Niedrige Besatzstärken (0,5 bis 1 GV/ha) und ausgeprägte Reliefierungen mit Sandrücken bzw. ‐kuppen im Gelände lassen das Problem aber in einem neuen Licht erscheinen. Die Tiere der Rasse DSR (Deutsches Schwarzbuntes Rind) wurden durch ungünstige Witterungsbedingungen nicht vom Grasen abgehalten. Sie hielten sich bei Nässe vorwiegend auf den höhergelegenen Flächen auf. Nach dem ersten Frost wurden vorzugsweise Brennesseln verbissen, später auch Disteln und Rohrglanzgras. Das TS‐reiche Weidefutter bedingt einen relativ hohen Tränkwasserverbrauch, der bei Frost noch ansteigen kann. Winter pasture on peat was till now unfavourable valueted in literature. Low stocking capacity (0,5–1,0 large animal units per hectare) and decidedly reliefation with sandy backs rsp. tops in the landscape lets the problem show in a new light. The animals of breed German black‐coloured cattle were no influenced by grasing through unfavourable weather conditions—She are holding by moisture mainly on the higher areas. After the first frost are feeded previously nettles, later thistles and red canary grass. The dry matter rich fodder use a relativ high water consume, which may increase by frost. The step demages stay low by large dimensioneted pastures (< 2% of area with long‐wearing damages of sward). Gaps are differently to value from the viewpoint of ecology. Established vegetation patterns will be broken up and new kinds obtain chances of development. Present itself possibility to take influence with the aim, to create a species reacher cover of vegetation. Through winter pasture are reached satisfactory agricultural results, when included effekt of landscape maintenance. Stichwörter: WinterweideNiedermoorLandschaftspflegeTrittschädenKeywords: Winter pasturepeatlandscape maintenancestep demage
Abstract Background A recently developed haemostatic peptide gel for endoscopic application has been introduced to improve the management of gastrointestinal bleeding. The aim of this pilot study was to evaluate the feasibility, safety, efficacy and indication profiles of PuraStat in a clinical setting. Methods In this prospective observational multicentre pilot study, patients with acute non-variceal gastrointestinal bleeding (upper and lower) were included. Primary and secondary application of PuraStat was evaluated. Haemoglobin, prothrombin time, platelets and transfusion behaviour were documented before and after haemostasis. The efficacy of PuraStat was assessed during the procedure, at 3 days and 1 week after application. Results 111 patients with acute gastrointestinal bleeding were recruited into the study. 70 percent (78/111) of the patients had upper gastrointestinal bleeding and 30% (33/111) had lower gastrointestinal bleeding. After primary application of PuraStat, initial haemostatic success was achieved in 94% of patients (74/79, 95% CI 88–99%), and in 75% of the patients when used as a secondary haemostatic product, following failure of established techniques (24/32, 95% CI 59–91%). The therapeutic success rates (absence of rebleeding) after 3 and 7 days were 91% and 87% after primary use, and 87% and 81% in all study patients. Overall rebleeding rate at 30 day follow-up was 16% (18/111). In the 5 patients who finally required surgery (4.5%), PuraStat allowed temporary haemostasis and stabilisation. Conclusions PuraStat expanded the therapeutic toolbox available for an effective treatment of gastrointestinal bleeding sources. It could be safely applied and administered without complications as a primary or secondary therapy. PuraStat may additionally serve as a bridge to surgery in order to achieve temporary haemostasis in case of refractory severe bleeding, possibly playing a role in preventing immediate emergency surgery.
Renal replacement therapy (RRT) is common. We undertook to develop and report some key performance indicators (KPIs) to monitor our provision of this costly therapy. We utilised data already collected in an electronic clinical information system that records the care received by our patients. We reduced our prescribed RRT dose to 25 ml/kg/hour in December 2011 following an appraisal of the literature [1]. We assessed whether the KPIs informed us if our practice changed and such changes were sustained.
