mediates pathogenic inflammatory responses to intestinal ischemia-reperfusion injury. Am J Physiol Gastrointest Liver Physiol 299: G833-G843, 2010. First published August 5, 2010 doi:10.1152/ajpgi.00065.2010.-Acute lung injury (ALI) and the development of the multiple organ dysfunction syndrome (MODS) are major causes of death in trauma patients. Gut inflammation and loss of gut barrier function as a consequence of splanchnic ischemia-reperfusion (I/R) have been implicated as the initial triggering events that contribute to the development of the systemic inflammatory response, ALI, and MODS. Since hypoxia-inducible factor (HIF-1) is a key regulator of the physiological and pathophysiological response to hypoxia, we asked whether HIF-1 plays a proximal role in the induction of gut injury and subsequent lung injury. Utilizing partially HIF-1␣-deficient mice in a global trauma hemorrhagic shock (T/HS) model, we found that HIF-1 activation was necessary for the development of gut injury and that the prevention of gut injury was associated with an abrogation of lung injury. Specifically, in vivo studies demonstrated that partial HIF-1␣ deficiency ameliorated T/HS-induced increases in intestinal permeability, bacterial translocation, and caspase-3 activation. Lastly, partial HIF-1␣ deficiency reduced TNF-␣, IL-1␤, cyclooxygenase-2, and inducible nitric oxide synthase levels in the ileal mucosa after T/HS whereas IL-1␤ mRNA levels were reduced in the lung after T/HS. This study indicates that prolonged intestinal HIF-1 activation is a proximal regulator of I/R-induced gut mucosal injury and gut-induced lung injury. Consequently, these results provide unique information on the initiating events in trauma-hemorrhagic shock-induced ALI and MODS as well as potential therapeutic insights. hemorrhagic shock; inflammation; multiple organ dysfunction syndrome; acute lung injury IN PATIENTS SUSTAINING major trauma, the development of the systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction (MODS) is a major clinical problem resulting in 50 -80% of all deaths in surgical intensive care units. Since the pathophysiology of this syndrome remains incompletely understood and therapy remains largely supportive (16), studies focusing on the basic biology of traumainduced SIRS, organ injury/dysfunction, and MODS have been major areas of investigation. These mechanistic studies have generated several working hypotheses, one of which is the gut hypothesis of MODS. A key element in the gut hypothesis of MODS is that a splanchnic ischemia-reperfusion (I/R) insult leading to gut inflammation and loss of barrier function is the initial triggering event that turns the gut into the "motor" of MODS (19). However, the exact mechanisms by which gut I/R leads to intestinal injury and how an intestinal ischemic insult is transduced into a systemic inflammatory response remains incomplete. To date, the majority of the molecular and cellular studies investigating shock-induced gut injury and gut-induced MODS have focused pr...

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.

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Whereas mural thrombus of the thoracic aorta is uncommon, it must be considered in the differential diagnosis of embolic events. Although endovascular therapy may be a useful first-line option for TAMT with reports of positive outcomes in select literature, further study of this treatment option is required.

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Unilateral LC results in the rapid mobilization of a significant number of HPC from the BM to the site of injury. BM function is maintained under this condition. The addition of HS increases HPC mobilization from the BM and sequestration at the site of injury as well as decreasing BM HPC growth. We postulate that the accumulation of progenitor cells in the injured tissue combined with an alteration of normal BM homing, as exemplified by the decrease in progenitor cells from the lung without restoration of BM function, plays a role in posttraumatic BM suppression. The mechanism of shock-mediated mobilization from the BM and the exact role and fate of these cells at the site of injury requires further investigation.

Adolescents undergoing supraclavicular decompression for NTOS had more favorable preoperative characteristics and enhanced 3-month and 6-month functional outcomes than adults. Further study is needed to delineate the age-dependent and independent factors that promote optimal surgical outcomes for NTOS.

DZ, Semenza GL, Deitch EA, Feinman R. Hypoxia-inducible factor plays a gut-injurious role in intestinal ischemia reperfusion injury. Am J Physiol Gastrointest Liver Physiol 300: G853-G861, 2011. First published December 23, 2010 doi:10.1152/ajpgi.00459.2010.-Gut injury and loss of normal intestinal barrier function are key elements in the paradigm of gutorigin systemic inflammatory response syndrome, acute lung injury, and multiple organ dysfunction syndrome (MODS). As hypoxiainducible factor (HIF-1) is a critical determinant of the physiological and pathophysiological response to hypoxia and ischemia, we asked whether HIF-1 plays a proximal role in the induction of gut injury and subsequent lung injury. Using partially HIF-1␣-deficient mice in an isolated superior mesenteric artery occlusion (SMAO) intestinal ischemia reperfusion (I/R) injury model (45 min SMAO followed by 3 h of reperfusion), we showed a direct relationship between HIF-1 activation and intestinal I/R injury. Specifically, partial HIF-1␣ deficiency attenuated SMAO-induced increases in intestinal permeability, lipid peroxidation, mucosal caspase-3 activity, and IL-1␤ mRNA levels. Furthermore, partial HIF-1␣ deficiency prevented the induction of ileal mucosal inducible nitric oxide synthase (iNOS) protein levels after SMAO and iNOS deficiency ameliorated SMAO-induced villus injury. Resistance to SMAO-induced gut injury was also associated with resistance to lung injury, as reflected by decreased levels of myeloperoxidase, IL-6 and IL-10 in the lungs of HIF-1␣ ϩ/Ϫ mice. In contrast, a short duration of SMAO (15 min) followed by 3 h of reperfusion neither induced mucosal HIF-1␣ protein levels nor caused significant gut and lung injury in wild-type or HIF-1␣ ϩ/Ϫ mice. This study indicates that intestinal HIF-1 activation is a proximal regulator of I/R-induced gut mucosal injury and gut-induced lung injury. However, the duration and severity of the gut I/R insult dictate whether HIF-1 plays a gut-protective or deleterious role.inflammation; inducible nitric oxide synthase; mucosal injury MULTIPLE ORGAN DYSFUNCTION syndrome (MODS) is the major cause of morbidity and mortality in critically ill patients. A key paradigm in the development of the systemic inflammatory response syndrome (SIRS) and acute respiratory distress syndrome (ARDS) that culminates in multiple organ dysfunction syndrome (MODS) is loss of intestinal barrier function (10, 12). Intestinal ischemia reperfusion (I/R) injury occurs in different clinical settings, such as trauma, shock, burn, mesenteric artery occlusion, abdominal, cardiac bypass, and thoracic vascular surgery, as well as small intestinal transplantation.Because the gut acts as the "motor" of SIRS, ARDS, and MODS (6) and therapy for the critically ill patient remains largely supportive, studies identifying the underlying pathophysiological factors in the gut that initiate and propagate SIRS, ARDS, and MODS are of critical importance. To date, studies investigating the gut inflammatory/injurious response have primarily fo...