Compromised IGF signaling causes caspase-6 activation in Huntington disease.

Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by an expansion of a polyglutamine repeat in the huntingtin (HTT) protein. Aberrant activation of caspase-6 and cleavage of mutant HTT generating the toxic N-terminal 586 HTT fragment are important steps in the pathogenesis of HD. Similarly, alterations in the insulin-like growth factor 1 (IGF-1) signaling pathway have been implicated in the disease as a result of decreased plasma IGF-1 levels in HD patients. In addition, two recent studies have demonstrated therapeutic benefit of IGF-1 treatment in mouse models of HD. Since IGF-1 promotes pro-survival pathways, we examined the relationship between IGF-1 signaling and aberrant caspase-6 activation in HD. Using immortalized mouse striatal cells expressing wild-type (STHdhQ7) or mutant HTT (STHdhQ111), we show that reduced levels of IGF-1 are associated with enhanced activation of caspase-6, increased cell death, and mutant HTT cleavage in a cellular stress paradigm. We demonstrate that IGF-1 supplementation reverses these effects and lowers the level of the toxic 586 HTT fragment. In addition, transcriptional analysis in the R6/2 HD transgenic mouse model demonstrated that the IGF-1 signaling system is dysregulated at multiple levels in several tissues including liver, muscle, and brain. Among these changes, we found increased expression of IGF-1 binding protein 3 (IGFBP-3), which may further reduce the bioavailability of IGF-1 as a consequence of increased IGF-1 binding. Our findings thus suggest that the therapeutic benefit of IGF-1 supplementation in HD may be significantly improved if other defects in the IGF-1 signaling pathway are corrected concurrently.

Proper Education on Spinal Orthotics: A Way to Minimize Associated Complications.

Spinal orthotic bracing is a common modality for treating nonoperative spinal fractures with risks. This study aimed to assess the effect of an intervention on critical care nurses to improve their clinical knowledge and comfort level of managing patients. A literature review was conducted regarding common complications associated with spinal orthotics. This information was compiled and used to create a questionnaire and spinal orthotic course for nurses. Pre- and postassessments of nurses' knowledge regarding spinal orthotics were conducted. A total of 197 nurses completed the presentation. The ability to correctly identify thoracolumbosacral orthotics (TLSO), lumbosacral orthotics (LSO) and cervico-thoracic orthotics (CTO) all significantly increased. Regarding the clinical knowledge, the right answer to the question whether or not halo vest needed to be removed for cardiopulmonary resuscitation increased from 45.2% to 100% (p < .0001), and the correct answer to the question whether or not TLSO braces need to be worn at all times in patients with spinal precautions increased from 62.4% to 100% (p < .0001). Nurses reported that their comfort level of taking care of patients with spinal precautions increased from 94.4% before the presentation to 100% after the presentation. The quality improvement project seemed to improve the critical care nurses' ability to correctly identify different type of braces and their comfort level of managing patients with spinal precautions.

Structural and solution studies of phenylbismuth(III) sulfonate complexes and their activity against Helicobacter pylori.

Three bis-phenylbismuth sulfonates [Ph(2)Bi(O(3)SR)](∞) (R = p-tolyl 1, mesityl 2 or S-(+)-10-camphoryl 3) have been synthesised and characterised. Their tendency for ligand redistribution in solution, and activity against the bacterium Helicobacter pylori have been investigated. The structures of 2 and 3 have been authenticated by X-ray diffraction crystallography. They are structurally very similar with polymeric helical chain structures composed of four coordinate Bi atoms which bridge between two sulfonate O atoms with near linear O-Bi-O bond angles. The two phenyl rings are cis to one another and trans to the stereochemically active lone pair. Upon dissolution of the pure compounds 1, 2 and 3, a ligand redistribution reaction occurs in which the mono-phenylbismuth bis-sulfonates, the bismuth tris-sulfonates and triphenylbismuth are formed. Two further complexes of general formula [PhBi(O(3)SR)(2)](∞) (where R = p-tolyl 4, and mesityl 5) were thus obtained and their crystal structures determined. The presence of the single sulfonato ligand in compounds 1, 2 and 3 resulted in a dramatic increase in bacteriocidial activity towards H. pylori (MIC values of ≥6.25 µg mL(-1)) relative to BiPh(3) (>64 µg mL(-1)) and the sulfonic acids, which were essentially inactive.

Evaluation of prehospital and emergency department systolic blood pressure as a predictor of in-hospital mortality.

Hypotension is a trauma activation criterion validated by multiple studies. However, field systolic blood pressures (SBP) are still met with skepticism. How significant is the role of prehospital (PH) and emergency department (ED) SBP in the patient's overall condition? A review of the trauma registry over a 5-year period was conducted. PH SBPs were stratified into four categories: severe (SBP 80 mmHg or less), moderate (81-100 mmHg), mild hypotension (101-120 mmHg), and normotension (greater than 120 mmHg). These four groups were further subcategorized into the patients who were hypotensive, SBP 90 mmHg or less in the ED, versus those that were not (SBP greater than 90 mmHg). Data for 6964 patients were analyzed. Patients with PH SBP of 80 mmHg or less compared with patients who had PH SBP of greater than 80 mmHg had higher mortality (OR, 9; 95% CI, 6.45-12.84). Patients with both PH SBP 80 mmHg or less and ED SBP 90 mmHg or less had the highest risk of mortality (50%) and highest need for emergent operative intervention (54%). PH and ED hypotension is a strong predictor of in-hospital mortality and need for emergent surgical intervention in trauma patients. Field or ED blood pressures should serve as a significant marker of the patient's condition.