Pancreatic ductal adenocarcinoma (PDAC) is associated with metaplastic changes in the pancreas but the transcriptional program underlying these changes is incompletely understood. The zinc finger transcription factor, PRDM3, is lowly expressed in normal pancreatic acini and its expression increases during tumorigenesis. Although PRDM3 promotes proliferation and migration of PDAC cell lines, the role of PRDM3 during tumor initiation from pancreatic acinar cells in vivo is unclear. In this study, we showed that high levels of PRDM3 expression in human pancreas was associated with pancreatitis, and well-differentiated but not poorly differentiated carcinoma. We examined PRDM3 function in pancreatic acinar cells during tumor formation and pancreatitis by inactivating Prdm3 using a conditional allele (Ptf1aCreER;Prdm3flox/flox mice) in the context of oncogenic Kras expression and supraphysiological cerulein injections, respectively. In Prdm3-deficient mice, KrasG12D-driven preneoplastic lesions were more abundant and progressed to high-grade precancerous lesions more rapidly. This is consistent with our observations that low levels of PRDM3 in human PDAC was correlated significantly with poorer survival in patient. Moreover, loss of Prdm3 in acinar cells elevated exocrine injury, enhanced immune cell activation and infiltration, and greatly increased acinar-to-ductal cell reprogramming upon cerulein-induced pancreatitis. Whole transcriptome analyses of Prdm3 knockout acini revealed that pathways involved in inflammatory response and Hif-1 signaling were significantly upregulated in Prdm3-depleted acinar cells. Taken together, our results suggest that Prdm3 favors the maintenance of acinar cell homeostasis through modulation of their response to inflammation and oncogenic Kras activation, and thus plays a previously unexpected suppressive role during PDAC initiation.In many rod-shaped bacteria, the actin homolog MreB directs cell-wall insertion and maintains cell shape, but it remains unclear how structural changes to MreB affect its organization in vivo. Here, we perform molecular dynamics simulations for Caulobacter crescentus MreB to extract mechanical parameters for inputs into a coarse-grained biophysical polymer model that successfully predicts MreB filament properties in vivo. Our analyses indicate that MreB double protofilaments can exhibit left-handed twisting that is dependent on the bound nucleotide and membrane binding; the degree of twisting correlates with the length and orientation of MreB filaments observed in vitro and in vivo. Our molecular dynamics simulations also suggest that membrane binding of MreB double protofilaments induces a stable membrane curvature of similar magnitude to that observed in vivo. Thus, our multiscale modeling correlates cytoskeletal filament size with conformational changes inferred from molecular dynamics simulations, providing a paradigm for connecting protein filament structure and mechanics to cellular organization and function.BACKGROUND Organ donation-rates using deceased donors and organizational approaches to organ donation differ drastically between countries at a similar level of health care as measured by the Euro Health Consumer Index (EHCI). MATERIAL AND METHODS Expert opinions from intensive care nurses, physicians, transplant coordinators and transplant surgeons from Austria, Germany, Spain, and the U.K. were obtained in semi-structured interviews followed by qualitative content analysis. Results were reported back to all interview partners to identify potential controversies and consensus recommendations. RESULTS No controversies could be detected. On a variety of beneficial factors an interprofessional consensus between interview partners could be reached A) The relevance of standardization of the screening for potential donors, the family approach and training; B) standards and best-practice procedures should be regulated and supervised by state authorities; C) full transparency and the prevention of scandals is essential; D) overburdened intensive care unit (ICU) doctors need to be supported by full-time in-house special nurses who organize donor evaluation, transport logistics and pastoral care, if required; E) public awareness campaigns are helpful; F) a broad public consensus on the concept of donation after brain and cardiac death is essential; G) incentives for the reporting of potential organ donors are inappropriate; H) an opt-out system alone is not sufficient. CONCLUSIONS Expert opinions from different professional backgrounds from different European health care systems reach a broad consensus on the most relevant issues for the improvement of organ donation.BACKGROUND Following total knee arthroplasty (TKA), postoperative patient rehabilitation is important to achieve the optimal level of knee function and mobility. Clinical research in this field is growing, and bibliometric analysis of publication may provide direction for research clinicians and raise awareness of research trends, journal selection, and key topics. Therefore, this bibliometric study aimed to analyze the current status and trends during the past two decades, between 1999 and 2018, of publications on rehabilitation after total knee arthroplasty (TKA) and used CiteSpace. MATERIAL AND METHODS The global literature was searched between 2018 to 2019 for publications related to rehabilitation after TKA. Publication data were identified using relevant search terms and the Web of Science Core Collection database. CiteSpace (5.3.R11) software was used to analyze the journals, authors, institutions, countries, cited references, and keywords using standard bibliometric indicators. RESULTS A total of 1,292 publications were retrieved between 1999 to 2018, and the most active journals, countries, authors, and institutions in the field of TKA rehabilitation were identified. Key areas of research included postoperative analgesia, muscle inhibition, range of motion, inhibitors, knee flexion, pain control, self-reporting, spectral analysis, in vivo forces, and rotator cuff repair.  https://www.selleckchem.com/products/c646.html  The emerging research topics included epidural analgesia, physiotherapy, postoperative analgesia, recovery, and the use of ropivacaine local analgesia. CONCLUSIONS The findings from this bibliometric study provided insight into trends in clinical research publications in the field of rehabilitation following TKA for the past 20 years, including global trends in emerging areas of research.