A 21-kDa leptospiral lipoprotein (LipL21) was evaluated for its diagnostic potential to detect bovine leptospirosis by ELISA. Both native LipL21 (nLipL21) and recombinant LipL21 (rLipL21) proteins were tested and compared regarding diagnostic efficiency, and no statistically significant difference was observed. The sensitivity of rLipL21 ELISA for 62 microscopic agglutination test (MAT) positive sera was 100% and the specificity with 378 MAT negative sera was 97.09%. Thus, rLipL21 protein-based ELISA could be used as an alternative to MAT for the diagnosis of bovine leptospirosis.

Novel supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) containing the poorly water-soluble drug halofantrine above equilibrium solubility (150% S(eq)) were compared in vitro and in vivo with conventional SNEDDS containing the drug below equilibrium solubility (75% S(eq)). Pre-concentrates comprising of either medium chain lipids (Captex 300/Capmul MCM) or long chain lipids (soybean oil/Maisine), Cremophor RH40 and ethanol were formulated maintaining the lipid-to-surfactant-to-cosolvent ratio constant (55:35:10, w/w %). The ability of super-SNEDDS to increase the absorption of halofantrine in dogs, as well as the predictivity of the dynamic in vitro lipolysis model was studied. In vitro lipolysis of SNEDDS and super-SNEDDS showed rapid drug precipitation from all formulations while the same drug concentrations in the digestion medium were found during digestion of equal amounts of SNEDDS and super-SNEDDS. Elevated halofantrine solubilisation during in vitro lipolysis was observed only when multiple capsules of conventional SNEDDS were subjected to in vitro digestion. After lipolysis the isolated super-SNEDDS pellets were characterised by XRPD revealing no crystalline halofantrine from any of the investigated formulations. Subsequent dissolution studies of the super-SNEDDS pellet in the lipolysis medium demonstrated enhanced dissolution of halofantrine suggesting that halofantrine in the pellet was amorphous. The enhanced dissolution of the amorphous halofantrine was also reflected in vivo since two capsules of conventional SNEDDS were needed to achieve similar AUC and C(max) as obtained after dosing of a single capsule of super-SNEDDS. The study demonstrated that the absorption of halofantrine was not hampered by drug precipitation. Super-SNEDDS lead to precipitation of halofantrine in an amorphous form, which can be the driving force for enhanced absorption. Since super-SNEDDS were also physically stable for at least 4months they represent a potential novel oral lipid-based drug delivery system for low aqueous soluble compounds.

BACKGROUND AND OBJECTIVES Pressure ulcers are commonly acquired in pediatric institutions, and they are a key indicator of the standard and effectiveness of care. We recognized a high rate of tracheostomy-related pressure ulcers (TRPUs) in our ventilator unit and instituted a quality improvement program to develop and test potential interventions for TRPU prevention, condensed them into a clinical bundle, and then implemented the bundle into our standard practice. METHODS The intervention model used a rapid-cycle, Plan-Do-Study-Act (PDSA), framework for improvement research. All tracheostomy-dependent patients admitted to our 18-bed ventilator unit from July 2008 through December 2010 were included. TRPU stage and description, number of days each TRPU persisted, and bundle compliance were recorded in real time. All TRPUs were staged by a wound-care expert within 24 hours. The interventions incorporated into the TRPU-prevention bundle included frequent skin and device assessments, moisture-reducing device interface, and pressure-free device interface. RESULTS There was a significant decrease in the rate of patients who developed a TRPU from 8.1% during the preintervention period, to 2.6% during bundle development, to 0.3% after bundle implementation. There was a marked difference between standard and extended tracheostomy tubes in TRPU occurrence (3.4% vs 0%, P =.007) and days affected by a TRPU (5.2% vs 0.1%, P <.0001). CONCLUSIONS Education and ongoing assessment of skin integrity and the use of devices that minimize pressure at the tracheostomy-skin interface effectively reduce TRPU even among a population of children at high risk. These interventions can be integrated into daily workflow and result in sustained effect.

Synapsin II is a synaptic vesicle-associated phosphoprotein that has been implicated in the pathophysiology of schizophrenia. Researchers have demonstrated reductions in synapsin II mRNA and protein in post-mortem prefrontal cortex and hippocampus samples from patients with schizophrenia. Synapsin II protein expression has been shown to be regulated by dopamine D(1) and D(2) receptor activation. Furthermore, behavioral testing of the synapsin II knockout mouse has revealed a schizophrenic-like behavioral phenotype in this mutant strain, suggesting a relationship between dysregulated and/or reduced synapsin II and schizophrenia. However, it remains unknown the specific regions of the brain of which perturbations in synapsin II play a role in the pathophysiology of this disease. The aim of this project was to evaluate animals with a selective knock-down of synapsin II in the medial prefrontal cortex through the use of siRNA technology. Two weeks after continuous infusion of synapsin II siRNAs, animals were examined for the presence of a schizophrenic-like behavioral phenotype. Our results reveal that rats with selective reductions in medial prefrontal cortical synapsin II demonstrate deficits in sensorimotor gating (prepulse inhibition), hyperlocomotion, and reduced social behavior. These results implicate a role for decreased medial prefrontal cortical synapsin II levels in the pathophysiology of schizophrenia and the mechanisms of aberrant prefrontal cortical circuitry, and suggest that increasing synapsin II levels in the medial prefrontal cortex may potentially serve as a novel therapeutic target for this devastating disorder.

OBJECTIVES: The purpose of this study was to review the MRI examinations of a large group of low-energy trauma patients in whom pelvic MRI had detected radiographically occult fractures, in order to characterize prevailing fracture patterns and determine how often co-existing proximal femoral and pelvic fractures were observed. METHODS: All patients having pelvic MRI over 5 years were identified. Word-search software selected 269 MRI reports containing the term 'fracture'. Further scrutiny identified 168 with diagnosis of fracture. MRI request and imaging record review identified 102 low-energy trauma cases that had MRI for clinical suspicion of fracture despite normal radiographs. Sixty-six cases were excluded for the following reasons: no expressed clinical suspicion of occult fracture; history suggesting high-energy trauma; skeletal co-morbidity hindering acute fracture identification; interval more than 2 weeks between radiographs and MRI. The 102 study MRI examinations, which employed a limited two-sequence protocol, were reviewed. Any fracture that had not been appreciated on radiographs was recorded and characterized as femoral, pelvic, or co-existing femoral and pelvic fractures. RESULTS: The 102 study cases had a median age of 82 years. The median interval between pelvic radiographs and MRI was 3 days. MRI showed undiagnosed femoral fracture in 48/102 cases (47.1%), sacral fracture in 41/102 (40.2%), and pubic fracture in 55/102 (53.9%). In 11/102 cases (10.8%), MRI showed undiagnosed fractures of both proximal femur and pelvic ring (seven sacral, six pubic bone, two other site fractures). In 10/11 cases with co-existing femoral and pelvic fractures, the femoral fracture was incomplete. CONCLUSIONS: Limited pelvic MRI found a high prevalence of radiographically occult femoral and pelvic fractures in low-energy trauma patients, with clinical suspicion of fracture despite normal radiographs. Co-existing occult femoral and pelvic ring fractures were commonly observed, and in such cases, the femoral fracture was likely to be incomplete and multiple pelvic fractures were typically present.

STUDY OBJECTIVES Sleep disordered breathing (SDB) is independently associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. Experimental sleep fragmentation has been shown to impair insulin sensitivity. Conventional electroencephalogram (EEG)-based sleep-quality measures have been inconsistently associated with indices of glucose metabolism. This analysis explored associations between glucose metabolism and an EEG-independent measure of sleep quality, the sleep spectrogram, which maps coupled oscillations of heart-rate variability and electrocardiogram (ECG)-derived respiration. The method allows improved characterization of the quality of stage 2 non-rapid eye movement (NREM) sleep. DESIGN Cross-sectional study. SETTING N/A. PARTICIPANTS Nondiabetic subjects with and without SDB (n = 118) underwent the frequently sampled intravenous glucose tolerance test (FSIVGTT) and a full-montage polysomnogram. The sleep spectrogram was generated from ECG collected during polysomnography. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Standard polysomnographic stages (stages 1, 2, 3+4, and rapid eye movement [REM]) were not associated with the disposition index (D(I)) derived from the FSIVGTT. In contrast, spectrographic high-frequency coupling (a marker of stable or "effective" sleep) duration was associated with increased, and very-low-frequency coupling (a marker of wake/REM/transitions) associated with reduced D(I). This relationship was noted after adjusting for age, sex, body mass index, slow wave sleep, total sleep time, stage 1, the arousal index, and the apnea-hypopnea index. CONCLUSIONS ECG-derived sleep-spectrogram measures of sleep quality are associated with alterations in glucose-insulin homeostasis. This alternate mode of estimating sleep quality could improve our understanding of sleep and sleep-breathing effects on glucose metabolism. CITATION: Pogach MS; Punjabi NM; Thomas N; Thomas RJ. Electrocardiogram-based sleep spectrogram measures of sleep stability and glucose disposal in sleep disordered breathing. SLEEP 2012;35(1):139-148.

Command hallucinations represent a special problem for the clinical management of psychosis. While compliance with both non-harmful and harmful commands can be problematic, sometimes in the extreme, active efforts to resist commands may also contribute to their malignancy. Previous research suggests Cognitive Behaviour Therapy (CBT) to be a useful treatment for reducing compliance with harmful command hallucinations. The purpose of this trial was to evaluate whether CBT augmented with acceptance-based strategies from Acceptance and Commitment Therapy could more broadly reduce the negative impact of command hallucinations. Forty-three participants with problematic command hallucinations were randomized to receive 15 sessions of the intervention "TORCH"(Treatment of Resistant Command Hallucinations) or the control, Befriending, then followed up for 6 months. A sub-sample of 17 participants was randomized to a waitlist control before being allocated to TORCH or Befriending. Participants engaged equally well with both treatments. Despite TORCH participants subjectively reporting greater improvement in command hallucinations compared to Befriending participants, the study found no significant group differences in primary and secondary outcome measures based on blinded assessment data. Within-group analyses and comparisons between the combined treatments and waitlist suggested, however, that both treatments were beneficial with a differential pattern of outcomes observed across the two conditions.

Images obtained by the Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS) cameras onboard the Rosetta spacecraft reveal that asteroid 21 Lutetia has a complex geology and one of the highest asteroid densities measured so far, 3.4 ± 0.3 grams per cubic centimeter. The north pole region is covered by a thick layer of regolith, which is seen to flow in major landslides associated with albedo variation. Its geologically complex surface, ancient surface age, and high density suggest that Lutetia is most likely a primordial planetesimal. This contrasts with smaller asteroids visited by previous spacecraft, which are probably shattered bodies, fragments of larger parents, or reaccumulated rubble piles.