Burn Center Organization and Cellular Therapy Integration: Managing Risks and Costs.

The complex management of severe burn victims requires an integrative collaboration of multidisciplinary specialists in order to ensure quality and excellence in healthcare. This multidisciplinary care has quickly led to the integration of cell therapies in clinical care of burn patients. Specific advances in cellular therapy together with medical care have allowed for rapid treatment, shorter residence in hospitals and intensive care units, shorter durations of mechanical ventilation, lower complications and surgery interventions, and decreasing mortality rates.

Massive Burns: Retrospective Analysis of Changes in Outcomes Indicators Across 18 Years.

The treatment and management of massive burns, defined as burns affecting at least 50% of total body surface area (TBSA), have considerably changed since the 1990s. This study aimed at analyzing if the length of intensive care unit (ICU) stay, the success of skin grafting operations, and the mortality changed in the past 18 years. Between 2000 and 2018, 77 patients were admitted for massive burns to the ICU of a university hospital.

Retrospective Evaluation of Progenitor Biological Bandage Use: A Complementary and Safe Therapeutic Management Option for Prevention of Hypertrophic Scarring in Pediatric Burn Care.

Progenitor Biological Bandages (PBB) have been continuously applied clinically in the Lausanne Burn Center for over two decades. Vast translational experience and hindsight have been gathered, specifically for cutaneous healing promotion of donor-site grafts and second-degree pediatric burns. PBBs constitute combined Advanced Therapy Medicinal Products, containing viable cultured allogeneic fetal dermal progenitor fibroblasts.

Antitumor activities of ATP-competitive inhibitors of mTOR in colon cancer cells.

Background: The mammalian target of rapamycin (mTOR) is frequently activated in colon cancers due to mutations in the phosphatidylinositol 3-kinase (PI3K) pathway. Targeting mTOR with allosteric inhibitors of mTOR such as rapamycin reduces colon cancer progression in several experimental models. Recently, a new class of mTOR inhibitors that act as ATP-competitive inhibitors of mTOR, has been developed.

Targeting renal cell carcinoma with NVP-BEZ235, a dual PI3K/mTOR inhibitor, in combination with sorafenib.

Background: Targeted therapies for metastatic renal cell carcinoma (RCC), including mammalian target of rapamycin (mTOR) inhibitors and small-molecule multikinase inhibitors, have produced clinical effects. However, most patients acquire resistance over time. Thus, new therapeutic strategies need to be developed.

Differential proteoglycan expression in two spinal cord regions after dorsal root injury.

Dorsal root injury leads to reactive gliosis in the spinal cord dorsal root entry zone and dorsal column, two regions that undergo Wallerian degeneration, but have distinct growth-inhibitory properties. This disparity could in part be due to differences in the number of degenerating sensory fibers, differences in glial cell activation, and/or to differential expression of growth-inhibitory molecules such as chondroitin sulfate proteoglycans. Laser capture microdissection of these two spinal cord white matter regions, followed by quantitative analysis of mRNA expression by real-time PCR, revealed that glial marker transcripts were differentially expressed post-injury and that the chondroitin sulfate proteoglycans Brevican and Versican V1 and V2 were preferentially up-regulated in the dorsal root entry zone, but not the dorsal column.

Myosin 5a controls insulin granule recruitment during late-phase secretion.

We have examined the importance of the actin-based molecular motor myosin 5a for insulin granule transport and insulin secretion. Expression of myosin 5a was downregulated in clonal INS-1E cells using RNAinterference. Stimulated hormone secretion was reduced by 46% and single-cell exocytosis, measured by capacitance recordings, was inhibited by 42% after silencing.

Role of phosphoinositide signaling in the control of insulin exocytosis.

Phosphoinositides (PI) are important signaling molecules involved in the regulation of vesicular trafficking. We found that phosphatidylinositol 4-phosphate (PI4P) and phosphatidylinositol 4,5-biphosphate [PI(4,5)P(2)] increase the secretory response triggered by 10 mum Ca(2+) in streptolysin-O-permeabilized insulin-secreting INS-1E cells. In addition, nutrient-induced exocytosis was diminished in intact cells expressing constructs that sequester PI(4,5)P(2) and in cells transfected with constructs that reduce by RNA interference the level of two enzymes involved in PI(4,5)P(2) production, type III PI4-kinase beta and type I phosphatidylinositol 4-bisphosphate 5-kinase-gamma.

Noc-king out exocrine and endocrine secretion.

The Rab GTPase effector Noc2 was brought into the limelight by a recent publication that demonstrated its requirements at different stages of regulated exocytosis. Noc2 knockout resulted in distinct abnormalities in endocrine and exocrine cells, ranging from the accumulation of secretory granules of increased size to impairments in the regulated release of their secretory products. Explanations for these defects are beginning to emerge and they promise to reveal some of the most jealously kept secrets of regulated exocytosis.

Involvement of the Rab27 binding protein Slac2c/MyRIP in insulin exocytosis.

Rab27a is a GTPase associated with insulin-containing secretory granules of pancreatic beta-cells. Selective reduction of Rab27a expression by RNA interference did not alter granule distribution and basal secretion but impaired exocytosis triggered by insulin secretagogues. Screening for potential effectors of the GTPase revealed that the Rab27a-binding protein Slac2c/MyRIP is associated with secretory granules of beta-cells.