SummaryRecent advances in human pluripotent stem cell (hPSC) differentiation protocols have generated insulin-producing cells resembling pancreatic β cells. While these stem cell-derived β (SC-β) cells are capable of undergoing glucose-stimulated insulin secretion (GSIS), insulin secretion per cell remains low compared with islets and cells lack dynamic insulin release. Herein, we report a differentiation strategy focused on modulating transforming growth factor β (TGF-β) signaling, controlling cellular cluster size, and using an enriched serum-free media to generate SC-β cells that express β cell markers and undergo GSIS with first- and second-phase dynamic insulin secretion. Transplantation of these cells into mice greatly improves glucose tolerance. These results reveal that specific time frames for inhibiting and permitting TGF-β signaling are required during SC-β cell differentiation to achieve dynamic function. The capacity of these cells to undergo GSIS with dynamic insulin release makes them a promising cell source for diabetes cellular therapy.
In this context, it could be assumed that experienced laparoscopic surgeons could perform robotic gastrectomy with a certain level of skill, even in initial series.
Quantitative characterization of the intracellular water 1 H magnetic resonance (MR) signal from cultured cells will provide critical biophysical insight into the MR signal from tissues in vivo. Microbeads provide a robust immobilization substrate for the many mammalian cell lines that adhere to surfaces and also provide sufficient cell density for observation of the intracellular water MR signal. However, selective observation of the intracellular water MR signal from perfused, microbead-adherent mammalian cells requires highly effective suppression of the extracellular water MR signal. We describe herein how high velocity perfusion of microbead-adherent cells results in short apparent 1 H MR longitudinal and transverse relaxation times for the extracellular water in a thin slice selected orthogonal to the direction of flow. When combined with a spin echo pulse sequence, this phenomenon provides highly effective suppression of the extracellular water MR signal. This new method is exploited herein to quantify the kinetics of water exchange from the intracellular to extracellular spaces for HeLa cells. The time constant describing water exchange from intracellular to extracellular spaces, also known as the exchange lifetime for intracellular water, is 119 ± 14 ms.
Background. The risk of recurrence and recurrence patterns after laparoscopy-assisted gastrectomy for gastric cancer remain unclear. The objective of this study is to assess recurrence and its timing, patterns, and risk factors following laparoscopy-assisted gastrectomy from multicenter data. Methods. A retrospective multicenter study was performed using data from 1,485 patients who had undergone laparoscopy-assisted gastrectomy for gastric cancer at ten institutions from 1998 to 2005. Recurrence and its timing and patterns were reviewed. Univariate and multivariate analyses were performed to identify risk factors for recurrence. Results. Excluding 68 patients (9 postoperative mortalities, 1 synchronous distant metastasis, 2 nonadenocarcinomas, and 56 losses to follow-up), 50 of 1,417 patients (3.5%) had recurrences. Incidence of recurrence was 1.6% (19/1186) in early gastric cancer and 13.4% (31/231) in advanced gastric cancer. Recurrence occurred in 34 of 50 patients (68.0%) within 2 years of surgery, and in 45 of 50 patients (90.0%) within 3 years. The recurrence pattern was hematogenous in 17 patients (34.0%), peritoneal in 11 (22.0%), locoregional in 10 (20.0%), distant lymph nodes in 2 (4.0%), and mixed in 10 (20.0%). Advanced T-classification and lymph node metastases were risk factors for recurrence. Conclusions. Laparoscopy-assisted gastrectomy showed satisfactory long-term oncologic outcomes similar to those of open surgery. The study provides additional evidence suggesting that laparoscopy-assisted gastrectomy is a good alternative to open gastrectomy in patients with gastric cancer of relatively early stage, although results of a randomized controlled trial and more long-term follow-up are needed to provide conclusive evidence.
Proper preoperative preparation and faultless surgical skills are required during initial surgery to reduce complications and the need for reoperation.
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