Blueprint for the development of resuscitation and emergency critical care fellowships.

The volume of critically ill patients presenting to the emergency department (ED) is increasing rapidly. Continued growth will likely further stress an already strained U.S. health care system. Numerous studies have demonstrated an association with worsened outcomes for critically ill patients boarding in the ED. To address the increasing volume and complexity of critically ill patients presenting to EDs nationwide, resuscitation and emergency critical care (RECC) fellowships were developed. RECC programs teach a general approach to the management of the undifferentiated critically ill patient, advanced management of critically ill patients by disease presentation, and ongoing supportive care of the critically ill patient boarding in the ED. The result is critical care training beyond that of a typical emergency medicine (EM) residency with a focus on the unique features and challenges of caring for critically ill patients in the ED not normally found in critical care fellowships. Graduates from RECC fellowships are well suited to practicing in any ED practice model and may be especially well prepared for EDs that distinguish acuity between zones (e.g., resuscitative care units, ED-based intensive care units). In addition to further developing clinical acumen, RECC fellowships provide graduates with a niche in EM education, research, and administration. In this article, we describe the philosophical principles and practical components necessary for the creation of future RECC fellowships.

Defining the role of syndecan-4 in mechanotransduction using surface-modification approaches.

The ability of cells to respond to external mechanical stimulation is a complex and robust process involving a diversity of molecular interactions. Although mechanotransduction has been heavily studied, many questions remain regarding the link between physical stimulation and biochemical response. Of significant interest has been the contribution of the transmembrane proteins involved, and integrins in particular, because of their connectivity to both the extracellular matrix and the cytoskeleton. Here, we demonstrate the existence of a mechanically based initiation molecule, syndecan-4. We first demonstrate the ability of syndecan-4 molecules to support cell attachment and spreading without the direct extracellular binding of integrins. We also examine the distribution of focal adhesion-associated proteins through controlling surface interactions of beads with molecular specificity in binding to living cells. Furthermore, after adhering cells to elastomeric membranes via syndecan-4-specific attachments we mechanically strained the cells via our mechanical stimulation and polymer surface chemical modification approach. We found ERK phosphorylation similar to that shown for mechanotransductive response for integrin-based cell attachments through our elastomeric membrane-based approach and optical magnetic twisting cytometry for syndecan-4. Finally, through the use of cytoskeletal disruption agents, this mechanical signaling was shown to be actin cytoskeleton dependent. We believe that these results will be of interest to a wide range of fields, including mechanotransduction, syndecan biology, and cell-material interactions.

Differential expression of unconventional myosins in apoptotic and regenerating chick hair cells confirms two regeneration mechanisms.

Hair cells of the inner ear are damaged by intense noise, aging, and aminoglycoside antibiotics. Gentamicin causes oxidative damage to hair cells, inducing apoptosis. In mammals, hair cell loss results in a permanent deficit in hearing and balance. In contrast, avians can regenerate lost hair cells to restore auditory and vestibular function. This study examined the changes of myosin VI and myosin VIIa, two unconventional myosins that are critical for normal hair cell formation and function, during hair cell death and regeneration. During the late stages of apoptosis, damaged hair cells are ejected from the sensory epithelium. There was a 4-5-fold increase in the labeling intensity of both myosins and a redistribution of myosin VI into the stereocilia bundle, concurrent with ejection. Two separate mechanisms were observed during hair cell regeneration. Proliferating supporting cells began DNA synthesis 60 hours after gentamicin treatment and peaked at 72 hours postgentamicin treatment. Some of these mitotically produced cells began to differentiate into hair cells at 108 hours after gentamicin (36 hours after bromodeoxyuridine (BrdU) administration), as demonstrated by the colabeling of myosin VI and BrdU. Myosin VIIa was not expressed in the new hair cells until 120 hours after gentamicin. Moreover, a population of supporting cells expressed myosin VI at 78 hours after gentamicin treatment and myosin VIIa at 90 hours. These cells did not label for BrdU and differentiated far too early to be of mitotic origin, suggesting they arose by direct transdifferentiation of supporting cells into hair cells.