Survival After Being Wedged in a Crevasse for 16 Hours in Alaska.

We present a case of an un-roped mountaineer who fell into a crevasse during descent from the summit of Denali (Mount McKinley). He was wedged about 20 m deep in the crevasse for a total of 16 h; this included 4.5 h waiting for a rescue team to arrive, and an 11.5 h extrication process. His condition deteriorated and he eventually lost consciousness. Even though the rescue team collectively felt there was little or no chance of survival, they continued until the victim was extricated from the crevasse. He was almost immediately placed in a hypothermia wrap with active warming, loaded on a rescue helicopter, and transported for 1 h 40 min to a hospital in Fairbanks, Alaska. During the flight, he was placed on supplemental oxygen. He was cold to the touch; respiration was detectable, but a pulse was not, and he was responsive to verbal stimuli. Initial bladder temperature in hospital was 26.1°C. He was released from hospital after 14 d and made a full recovery. This case highlights an important mix of preventative and resuscitative lessons regarding crevasse rescue in an isolated location. The lessons include the dangers of travelling un-roped on a crevassed glacier, the challenges of extrication from a confined space, the fact that respirations are often more easily detected than pulses, an extended transport time to medical facilities, and the necessity of trying unorthodox extrication methods. This case emphasized the need to continue extrication and treatment efforts for a cold patient even when survival with hypothermia seems impossible.

The proteomic and metabolomic signatures of isolated and polytrauma traumatic brain injury.

BACKGROUND: The interactions of polytrauma, shock, and traumatic brain injury (TBI) on thromboinflammatory responses remain unclear and warrant investigation as we strive towards personalized medicine in trauma. We hypothesized that comprehensive omics characterization of plasma would identify unique metabolic and thromboinflammatory pathways following TBI. METHODS: Patients were categorized as TBI vs Non-TBI, and stratified into Polytrauma or minimally injured. Discovery 'omics was employed to quantify the top differently expressed proteins and metabolites of TBI and Non-TBI patient groups. RESULTS: TBI compared to Non-TBI showed gene enrichment in coagulation/complement cascades and neuronal markers. TBI was associated with elevation in glycolytic metabolites and conjugated bile acids. Division into isolated TBI vs polytrauma showed further distinction of proteomic and metabolomic signatures. CONCLUSION: Identified mediators involving in neural inflammation, blood brain barrier disruption, and bile acid building leading to TBI associated coagulopathy offer suggestions for follow up mechanistic studies to target personalized interventions.

VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity.

BACKGROUND: This work tests the hypothesis that bladder instillation with vascular endothelial growth factor (VEGF) modulates sensory and motor nerve plasticity, and, consequently, bladder function and visceral sensitivity.In addition to C57BL/6J, ChAT-cre mice were used for visualization of bladder cholinergic nerves. The direct effect of VEGF on the density of sensory nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1) and cholinergic nerves (ChAT) was studied one week after one or two intravesical instillations of the growth factor.To study the effects of VEGF on bladder function, mice were intravesically instilled with VEGF and urodynamic evaluation was assessed. VEGF-induced alteration in bladder dorsal root ganglion (DRG) neurons was performed on retrogradly labeled urinary bladder afferents by patch-clamp recording of voltage gated Na+ currents. Determination of VEGF-induced changes in sensitivity to abdominal mechanostimulation was performed by application of von Frey filaments. RESULTS: In addition to an overwhelming increase in TRPV1 immunoreactivity, VEGF instillation resulted in an increase in ChAT-directed expression of a fluorescent protein in several layers of the urinary bladder. Intravesical VEGF caused a profound change in the function of the urinary bladder: acute VEGF (1 week post VEGF treatment) reduced micturition pressure and longer treatment (2 weeks post-VEGF instillation) caused a substantial reduction in inter-micturition interval. In addition, intravesical VEGF resulted in an up-regulation of voltage gated Na(+) channels (VGSC) in bladder DRG neurons and enhanced abdominal sensitivity to mechanical stimulation. CONCLUSIONS: For the first time, evidence is presented indicating that VEGF instillation into the mouse bladder promotes a significant increase in peripheral nerve density together with alterations in bladder function and visceral sensitivity. The VEGF pathway is being proposed as a key modulator of neural plasticity in the pelvis and enhanced VEGF content may be associated with visceral hyperalgesia, abdominal discomfort, and/or pelvic pain.

Using systems of care to reduce incarceration of youth with serious mental illness.

Youth with serious mental illness come into contact with juvenile justice more than 3 times as often as other youth, obliging communities to expend substantial resources on adjudicating and incarcerating many who, with proper treatment, could remain in the community for a fraction of the cost. Incarceration is relatively ineffective at remediating behaviors associated with untreated serious mental illness and may worsen some youths' symptoms and long-term prognoses. Systems of care represent a useful model for creating systems change to reduce incarceration of these youth. This paper identifies the systemic factors that contribute to the inappropriate incarceration of youth with serious mental illness, including those who have committed non-violent offenses or were detained due to lack of available treatment. It describes the progress of on-going efforts to address this problem including wraparound and diversion programs and others utilizing elements of systems of care. The utility of systems of care principles for increasing access to community-based mental health care for youth with serious mental illness is illustrated and a number of recommendations for developing collaborations with juvenile justice to further reduce the inappropriate incarceration of these youth are offered.

Impaired Cellular Immunity in the Murine Neural Crest Conditional Deletion of Endothelin Receptor-B Model of Hirschsprung's Disease.

Hirschsprung's disease (HSCR) is characterized by aganglionosis from failure of neural crest cell (NCC) migration to the distal hindgut. Up to 40% of HSCR patients suffer Hirschsprung's-associated enterocolitis (HAEC), with an incidence that is unchanged from the pre-operative to the post-operative state. Recent reports indicate that signaling pathways involved in NCC migration may also be involved in the development of secondary lymphoid organs. We hypothesize that gastrointestinal (GI) mucosal immune defects occur in HSCR that may contribute to enterocolitis. EdnrB was deleted from the neural crest (EdnrBNCC-/-) resulting in mutants with defective NCC migration, distal colonic aganglionosis and the development of enterocolitis. The mucosal immune apparatus of these mice was interrogated at post-natal day (P) 21-24, prior to histological signs of enterocolitis. We found that EdnrBNCC-/- display lymphopenia of their Peyer's Patches, the major inductive site of GI mucosal immunity. EdnrBNCC-/- Peyer's Patches demonstrate decreased B-lymphocytes, specifically IgM+IgDhi (Mature) B-lymphocytes, which are normally activated and produce IgA following antigen presentation. EdnrBNCC-/- animals demonstrate decreased small intestinal secretory IgA, but unchanged nasal and bronchial airway secretory IgA, indicating a gut-specific defect in IgA production or secretion. In the spleen, which is the primary source of IgA-producing Mature B-lymphocytes, EdnrBNCC-/- animals display decreased B-lymphocytes, but an increase in Mature B-lymphocytes. EdnrBNCC-/- spleens are also small and show altered architecture, with decreased red pulp and a paucity of B-lymphocytes in the germinal centers and marginal zone. Taken together, these findings suggest impaired GI mucosal immunity in EdnrBNCC-/- animals, with the spleen as a potential site of the defect. These findings build upon the growing body of literature that suggests that intestinal defects in HSCR are not restricted to the aganglionic colon but extend proximally, even into the ganglionated small intestine and immune cells.