Supramolecular interactions in PuO2Cl4(2-) and PuCl6(2-) complexes with protonated pyridines: synthesis, crystal structures, and Raman spectroscopy.

The synthesis, crystal structures, and Raman spectra of seven plutonium chloride compounds are presented. The materials are based upon Pu(VI)O2Cl4(2-) and Pu(IV)Cl6(2-) anions that are charge balanced by protonated pyridinium cations. The single crystal X-ray structures show a variety of donor-acceptor interactions between the plutonium perhalo anions and the cationic pyridine groups. Complementary Raman spectra show that these interactions can be probed through the symmetric vibrational mode of the plutonyl moiety. Unlike previously reported studies in similar uranyl(VI) systems, the facile redox chemistry of plutonium in aqueous solution has demonstrated the feasibility of using not only the An(VI)O2Cl4(2-) anion with approximate D4h symmetry but also the approximately Oh An(IV)Cl6(2-) anion in order to manipulate both the structure and dimensionality of such hybrid materials.

Augmenting cognitive behaviour therapy for post-traumatic stress disorder with emotion tolerance training: a randomized controlled trial.

BACKGROUND: Many patients do not adhere to or benefit from cognitive behaviour therapy (CBT) for post-traumatic stress disorder (PTSD). This randomized controlled trial evaluates the extent to which preparing patients with emotion regulation skills prior to CBT enhances treatment outcome. METHOD: A total of 70 adult civilian patients with PTSD were randomized to 12 sessions of either supportive counselling followed by CBT (Support/CBT) or emotion regulation training followed by CBT (Skills/CBT). RESULTS: Skills/CBT resulted in fewer treatment drop-outs, less PTSD and anxiety, and fewer negative appraisals at 6 months follow-up than Support/CBT. Between-condition effect size was moderate for PTSD severity (0.43, 95% confidence interval x0.04 to 0.90). More Skills/CBT (31%) patients achieved high end-state functioning at follow-up than patients in Support/CBT (12%) [Χ2(n=70)=3.67, p<0.05]. CONCLUSIONS: This evidence suggests that response to CBT may be enhanced in PTSD patients by preparing them with emotion regulation skills. High attrition of participants during the study limits conclusions from this study.

Structural studies coupling X-ray diffraction and high-energy X-ray scattering in the UO2(2+)-HBr(aq) system.

The structural chemistry of uranium(VI) in concentrated aqueous hydrobromic acid solutions was investigated using both single crystal X-ray diffraction and synchrotron-based high-energy X-ray scattering (HEXS) to reveal the structure of the uranium(VI) complexes in solution prior to crystallization. The crystal structures of a series of uranyl tetrabromide salts are reported, including Cs(2)UO(2)Br(4), Rb(2)UO(2)Br(4)·2H(2)O, K(2)UO(2)Br(4)·2H(2)O, and (NH(4))(2)UO(2)Br(4)·2H(2)O, as well as a molecular dimer of uranium(VI), (UO(2))(2)(OH)(2)Br(2)(H(2)O)(4). Limited correspondence exists between the structures observed in the solid state and those in solution. Quantitative analysis of the HEXS data show an average U-Br coordination number of 1.9(2) in solution, in contrast to the U-Br coordination number of 4 in the solid salts.

ISIS Penning source extraction studies reveal the 3-dimensional Child-Langmuir effect.

The standard 1X ISIS negative Penning surface plasma source has reliably produced an H- beam for ISIS operations for 35 years. In order to meet the 60 mA, 2 ms, and 50 Hz beam current and duty cycle required for the front end test stand (Letchford et al., in Proceedings of IPAC2015, Richmond, VA, USA, 2015), a 2X scaled source has been developed [Faircloth et al., AIP Conf. Proc. 2052, 050004 (2018)]. The 2X source has a plasma chamber twice the linear dimensions of the 1X source. This paper investigates the comparison between different emission areas (plasma electrode aperture dimensions) for both the 1X and 2X sources. Slit and circular extraction schemes are studied. A 3D Child-Langmuir relationship is observed where the space charge limited current density depends on the aspect ratio of the extraction aperture.

Sensory neuron and substance P involvement in symptoms of a zymosan-induced rat model of acute bowel inflammation.

Intestinal inflammation is a painful syndrome with multiple symptoms, including chronic pain. This study examined the possible role of sensory neurons and substance P in symptoms of an animal model of acute intestinal inflammation. The model was induced by injecting ethanol and zymosan into the colon of anesthetized male rats. Three hours later, sections of the colon were stained with hematoxylin and eosin. To determine the role of substance P, 5 mg/kg of the neurokinin-1 receptor (NK-1r) antagonist, CP-96,345, or 300 microg/kg of an antisense oligonucleotide targeted at NK-1r mRNA was administered. Spinal cord sections were examined for internalization of NK-1r, as an indicator of substance P release. Sections of colon revealed infiltration of inflammatory cells following ethanol and zymosan treatment. Plasma extravasation in rats given ethanol and zymosan was significantly greater than in controls given saline only (P<0.0001) or saline and ethanol (P<0.001). In ethanol- and zymosan-treated rats given CP-96,345, plasma extravasation was significantly less than in rats given ethanol and zymosan without the antagonist (P<0.0001). Administration of the antisense oligonucleotide also resulted in lower levels of plasma extravasation compared with controls (P<0.01). Internalization of the NK-1r was observed in neurons of lamina I in the T13-L2 and L6-S2 regions of the spinal cord, as well as in sympathetic preganglionic neurons at the L1 level. This internalization was observed in the absence of any other stimulus besides the inflammation itself. This study implicates substance P and its receptor, the NK-1r, in acute inflammation of the colon.

Morphine priming in rats with chronic inflammation reveals a dichotomy between antihyperalgesic and antinociceptive properties of deltorphin.

We previously showed that prolonged morphine treatment and chronic inflammation both enhanced delta opioid receptor (deltaOR) cell surface density in lumbar spinal cord neurons. Here, we sought to determine whether administration of morphine to rats with chronic inflammation would further increase the bio-availability of deltaOR, and thereby the analgesic properties of the deltaOR agonist deltorphin, over that produced by inflammation alone. We found that chronic inflammation produced by injection of complete Freund's adjuvant (CFA) into the hind paw resulted in a bilateral increase in the binding and internalization of fluorescent deltorphin in neurons of the lumbar spinal cord as did prolonged morphine treatment [Morinville A, Cahill CM, Aibak H, Rymar VV, Pradhan A, Hoffert C, Mennicken F, Stroh T, Sadikot AF, O'Donnell D, Clarke PB, Collier B, Henry JL, Vincent JP, Beaudet A (2004a) Morphine-induced changes in delta opioid receptor trafficking are linked to somatosensory processing in the rat spinal cord. J Neurosci 24:5549-5559]. This effect was accompanied by an increase in the antinociceptive efficacy of intrathecal deltorphin as measured using the tail-flick test. Treatment of CFA-injected rats with morphine decreased the cell surface availability of deltaOR in neurons of the dorsal horn of the lumbar spinal cord as compared with treatment with CFA alone. Behaviorally, it significantly enhanced the antihyperalgesic effects of deltorphin (plantar test; % maximum possible antihyperalgesic effect (MPAHE)=113.5%+/-32.4% versus 26.1%+/-11.6% in rats injected with CFA alone) but strongly reduced the antinociceptive efficacy of the drug (tail-flick test; % maximum possible antinociceptive effect (MPE)=29.6%+/-3.6% versus 66.6%+/-6.3% in rats injected with CFA alone) suggesting that the latter, but not the former, is linked to the deltaOR trafficking events observed neuroanatomically. These results demonstrate that in chronic inflammation, the antihyperalgesic effects of deltaOR agonists may be enhanced by morphine pre-treatment. They also reveal a dichotomy between mechanisms underlying antihyperalgesic and antinociceptive effects of deltaOR agonists.

Prolonged morphine treatment targets delta opioid receptors to neuronal plasma membranes and enhances delta-mediated antinociception.

Opioid receptors are known to undergo complex regulatory changes in response to ligand exposure. In the present study, we examined the effect of morphine on the in vitro and in vivo density and trafficking of delta opioid receptors (deltaORs). Prolonged exposure (48 hr) of cortical neurons in culture to morphine (10 microm) resulted in a robust increase in the internalization of Fluo-deltorphin, a highly selective fluorescent deltaOR agonist. This effect was mu-mediated because it was entirely blocked by the selective mu opioid receptor antagonist d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH(2) and was reproduced using the selective mu agonist fentanyl citrate. Immunogold electron microscopy revealed a marked increase in the cell surface density of deltaORs in neurons exposed to morphine, indicating that the increase in Fluo-deltorphin internalization was caused by increased receptor availability. Prolonged morphine exposure had no effect on deltaOR protein levels, as assessed by immunocytochemistry and Western blotting, suggesting that the increase in bioavailable deltaORs was caused by recruitment of reserve receptors from intracellular stores and not from receptor neosynthesis. Complementary in vivo studies demonstrated that chronic treatment of adult rats with morphine (5-15 mg/kg, s.c., every 12 hr) similarly augmented targeting of deltaORs to neuronal plasma membranes in the dorsal horn of the spinal cord. Furthermore, this treatment markedly potentiated intrathecal d-[Ala(2)]deltorphin II-induced antinociception. Taken together, these results demonstrate that prolonged stimulation of neurons with morphine markedly increases recruitment of intracellular deltaORs to the cell surface, both in vitro and in vivo. We propose that this type of receptor subtype cross-mobilization may widen the transduction repertoire of G-protein-coupled receptors and offer new therapeutic strategies.

Prolonged morphine treatment alters δ opioid receptor post-internalization trafficking.

BACKGROUND AND PURPOSE: The δ opioid receptor (DOP receptor) undergoes internalization both constitutively and in response to agonists. Previous work has shown that DOP receptors traffic from intracellular compartments to neuronal cell membranes following prolonged morphine treatment. Here, we examined the effects of prolonged morphine treatment on the post-internalization trafficking of DOP receptors. EXPERIMENTAL APPROACH: Using primary cultures of dorsal root ganglia neurons, we measured the co-localization of endogenous DOP receptors with post-endocytic compartments following both prolonged and acute agonist treatments. KEY RESULTS: A departure from the constitutive trafficking pathway was observed following acute DOP receptor agonist-induced internalization by deltorphin II. That is, the DOP receptor underwent distinct agonist-induced post-endocytic sorting. Following prolonged morphine treatment, constitutive DOP receptor trafficking was augmented. SNC80 following prolonged morphine treatment also caused non-constitutive DOP receptor agonist-induced post-endocytic sorting. The µ opioid receptor (MOP receptor) agonist DAMGO induced DOP receptor internalization and trafficking following prolonged morphine treatment. Finally, all of the alterations to DOP receptor trafficking induced by both DOP and MOP receptor agonists were inhibited or absent when those agonists were co-administered with a DOP receptor antagonist, SDM-25N. CONCLUSIONS AND IMPLICATIONS: The results support the hypothesis that prolonged morphine treatment induces the formation of MOP-DOP receptor interactions and subsequent augmentation of the available cell surface DOP receptors, at least some of which are in the form of a MOP/DOP receptor species. The pharmacology and trafficking of this species appear to be unique compared to those of its individual constituents. LINKED ARTICLES: This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.

Anti-nociception mediated by a κ opioid receptor agonist is blocked by a δ receptor agonist.

BACKGROUND AND PURPOSE: The opioid receptor family comprises four structurally homologous but functionally distinct sub-groups, the µ (MOP), δ (DOP), κ (KOP) and nociceptin (NOP) receptors. As most opioid agonists are selective but not specific, a broad spectrum of behaviours due to activation of different opioid receptors is expected. In this study, we examine whether other opioid receptor systems influenced KOP-mediated antinociception. EXPERIMENTAL APPROACH: We used a tail withdrawal assay in C57Bl/6 mice to assay the antinociceptive effect of systemically administered opioid agonists with varying selectivity at KOP receptors. Pharmacological and genetic approaches were used to analyse the interactions of the other opioid receptors in modulating KOP-mediated antinociception. KEY RESULTS: Etorphine, a potent agonist at all four opioid receptors, was not anti-nociceptive in MOP knockout (KO) mice, although etorphine is an efficacious KOP receptor agonist and specific KOP receptor agonists remain analgesic in MOP KO mice. As KOP receptor agonists are aversive, we considered KOP-mediated antinociception might be a form of stress-induced analgesia that is blocked by the anxiolytic effects of DOP receptor agonists. In support of this hypothesis, pretreatment with the DOP antagonist, naltrindole (10 mg·kg(-1) ), unmasked etorphine (3 mg·kg(-1) ) antinociception in MOP KO mice. Further, in wild-type mice, KOP-mediated antinociception by systemic U50,488H (10 mg·kg(-1) ) was blocked by pretreatment with the DOP agonist SNC80 (5 mg·kg(-1) ) and diazepam (1 mg·kg(-1) ). CONCLUSIONS AND IMPLICATIONS: Systemic DOP receptor agonists blocked systemic KOP antinociception, and these results identify DOP receptor agonists as potential agents for reversing stress-driven addictive and depressive behaviours mediated through KOP receptor activation. LINKED ARTICLES: This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.

Apoptosis participates in the remodeling of the endocrine pancreas in the neonatal rat.

In rodents, shortly after birth a lack of increase in pancreatic weight and in islet mass have been reported during a time of overall body weight increase. To understand this regulation of the neonatal growth of the beta cell mass, we studied Sprague Dawley rats at 2, 9, 13, 17, 20, 24, and 31 days of age for beta cell replication, beta cell mass, and cell size and for the presence of cell apoptosis. beta cell mass was stable from 2-20 days (range: 0.91 +/- 0.2 to 1.33 +/- 0.23 mg) and increased thereafter. beta cell replication progressively decreased. Condensed apoptotic nuclei were identified and counted on paraffin sections using the fluorescent dye propidium iodide. Apoptotic beta cell nuclei were found at a basal rate (1.54 +/- 0.22%) at 2, 9, and again after 20 days of age. However, at 13 and 17 days, the incidence of apoptosis was significantly increased (3.64 +/- 0.45%). The decreased replication and the increased incidence of apoptosis in the beta cells strongly suggest a wave of neogenesis of beta cells to maintain the constant beta cell mass. These data show that the endocrine pancreas undergoes significant modification during neonatal life and that apoptosis is an important mechanism in this remodeling of the beta cell mass. Whether a selective deletion of some population of beta cells occurs is unclear, but a dysregulation of this remodeling process could have important effects on the pancreatic beta cell mass.

Glucagon-like peptide-1 regulates the beta cell transcription factor, PDX-1, in insulinoma cells.

Glucagon-like peptide-1 (GLP-1) enhances insulin biosynthesis and secretion as well as transcription of the insulin, GLUT2 and glucokinase genes. The latter are also regulated by the PDX-1 homeoprotein. We investigated the possibility that GLP-1 may be having its long-term pleiotropic effects through a hitherto unknown regulation of PDX-1. We found that PDX-1 mRNA level was significantly increased (p<0.01) after 2 hours and insulin mRNA level was subsequently increased (p<0.01) after 3 hours of treatment with GLP-1 (10 nM) in RIN 1046-38 insulinoma cells. Under these experimental conditions, there was also a 1.6-fold increase in the expression of PDX-1 protein in whole cell and nuclear extracts. Overexpression of PDX-1 in these cells confirmed the finding of the wild type cells such that GLP-1 induced a 2-fold increase in whole cell extracts and a 3-fold increase in nuclear extracts of PDX-1 protein levels. The results of electrophoretic mobility shift experiments showed that PDX-1 protein binding to the Al element of the rat insulin II promoter was also increased 2 h post treatment with GLP-1. In summary, we have uncovered a previously unknown aspect to the regulation of PDX-1 in beta cells. This has important implications in the physiology of adult beta cells and the treatment of type 2 diabetes mellitus with GLP-1 or its analogs.

Human plasma beta-endorphin-like peptides: a rapid, high recovery extraction technique and validation of radioimmunoassay.

This is a report of the development, calibration, and validation of a series of techniques required to measure beta-endorphin (beta-END)-like immunoreactivity in human plasma, including sieve and affinity chromatography. The RIA, which uses the antibody Brenda, is very sensitive (IC50 = 5-15 fmol/tube at a final concentration of 1:40,000). The extraction process, which uses the Sep-Pak C18 cartridge (Waters Associates, Inc.), is simple and rapid and has a recovery rate of more than 90%. It extracts proopiomelanocortin, beta-lipotropin, and beta-END. Physiological validation was provided by the measurement of beta-END-like immunoreactivity in a pool of plasma of normal humans (2.25 fmol/ml plasma), two pregnant women at term (9.5 and 10.75 fmol/ml), and one patient with Nelson's disease (2 pmol/ml plasma).

Imaging transient, randomly occurring neuropsychological events in single subjects with positron emission tomography: an event-related count rate correlational analysis.

Many neuropsychiatric symptom states are idiosyncratic, involuntary, randomly occurring, subjective, and transient. The brain states associated with these clinically important mental states cannot be imaged directly with existing positron emission tomography (PET) techniques. A new PET method that brings such mental/brain states under experimental control for analysis in single subjects is described. It utilizes a slow bolus H2 15O three-dimensional (3D) regional CBF imaging technique. The analysis focuses upon natural or experimentally induced variance in the temporal distribution of specific neuropsychological events over the course of a study session. For each scan, the amount of radioactivity entering the brain during these events is calculated to derive a score reflecting the contribution of the events to the image. A statistical analysis is then performed to identify those pixels in which the intensity covaries with the scan scores over the subject's scans. This permits the identification of the brain areas associated with the mental state of interest. The method is validated using an auditory sentence-monitoring task. The detection in single subjects of cerebral activations associated with recurrent events as brief as 2 s in duration is demonstrated. This method may be used as a means of imaging ephemeral neurologic or neuropsychiatric symptom states or as an alternative to a subtraction design for activation studies.

Detection of thirty-second cognitive activations in single subjects with positron emission tomography: a new low-dose H2(15)O regional cerebral blood flow three-dimensional imaging technique.

Positron emission tomography regional CBF (rCBF) studies of cognitive processes have traditionally required 30-60 mCi of H2(15)O per scan and intersubject averaging to achieve statistical significance. However, intersubject anatomical, functional, and disease variability can make such an approach problematic. A new method that produces significant results in single subjects is presented. It is based upon high-sensitivity three-dimensional imaging and a "slow" bolus administration of < 15 mCi of H2(15)O per scan. The method is validated in four normal volunteers using control and auditory-language activation tasks with four scans per condition and statistical parametric mapping analysis. It is demonstrated that the rCBF distribution associated with the cognitive state is detected during the arrival of radiotracer in the brain. This occurs over 30 s and constitutes a critical temporal window during which stimulation should be performed. A 90-s acquisition time is found to produce results of greater significance than a 60-s acquisition time. The implications of the results and the functional neuroanatomical findings are discussed. This method is suitable for the study of individual functional neuroanatomy in many neuropsychological, pharmacologic, and symptom states in normal subjects and in patients with psychiatric and neurologic disorders.

Long term effects of callosal lesions in the auditory cortex of rats of different ages.

The corpus callosum was sectioned in groups of rats 3, 12, and 24 months of age, and the auditory cortex was examined three months later to determine whether there were age-related differences in the morphological response to the partial deafferentation. Material from the three groups of long-term callosally-lesioned rats were compared with three groups of age-matched control animals. Analysis focused on those cortical layers known to receive the heaviest callosal projection (layers II and III) and those neurons known to be postsynaptic to callosal afferents (layer V pyramidal neurons). There were no age-related changes in cortical thickness or in the relative thickness of the cortical layers in the control groups. However, the apical dendrites of layer V pyramidal neurons did lose dendritic spines and became thinner with age. In all three lesion groups, the cortex became thinner without altering the relative thickness of cortical layers; there was a decrease in the relative density of apical dendrite spines in layer III, but an increase in the density of these spines in layer IV. Both effects varied with age. Spine decreases in layer III were greatest in older animals and spine increases in layer IV were greatest in younger animals. The mean diameters of apical dendrites decreased in the youngest group of lesioned animals but increased in the oldest group. The results indicate that the effects of callosal deafferentation are age dependent.

Immunohistochemical distribution of delta opioid receptors in the rat central nervous system: evidence for somatodendritic labeling and antigen-specific cellular compartmentalization.

Many studies have reported on the distribution of delta opioid receptors (delta OR) in the mammalian central nervous system (CNS) by using a variety of techniques. However, no general consensus has emerged with regards to the localization of this receptor due to inconsistencies in the immunohistochemical literature. In the present study, we analyzed the cellular and subcellular distribution of immunoreactive delta OR in the rat CNS using two different antibodies (directed against a sequence in the C-terminus or N-terminus of the rat delta OR). By using Western blotting, these two antibodies recognized similar forms of the delta OR in COS-7 cells transfected with this receptor, but distinct forms in membranes from the rat spinal cord. By using light microscopic immunohistochemistry, both antibodies recognized identical populations of nerve cell bodies throughout the CNS; the distribution of these cell bodies conformed to that of delta OR mRNA-expressing cells detected by in situ hybridization. However, whereas the C-terminus-directed antibody recognized predominantly perikarya and proximal dendrites, the N-terminus-directed antibody also labeled extensively dendritic and terminal arbors. Furthermore, by using electron microscopy, the two antibodies were found not only to label differentially somatodendritic versus axonal compartments, but also plasma membrane versus cytoplasmic ones, suggesting that distinct immunological forms of the receptor are being targeted preferentially to different cellular and subcellular domains.

Up-regulation and trafficking of delta opioid receptor in a model of chronic inflammation: implications for pain control.

Pharmacological and physiological evidence supports a role for delta (delta) opioid receptors in the nociceptive mechanisms of inflammation. However, few data exist regarding delta opioid receptor expression and localization in such conditions. In this study, we have assessed the distribution and function of delta opioid receptors in the rat spinal cord following induction of chronic inflammation by intraplantar injection of complete Freund's adjuvant (CFA). Intrathecal administration of the selective delta opioid receptor agonist, D-[Ala(2), Glu(4)] deltorphin, dose-dependently reversed thermal hyperalgesia induced by CFA. In situ hybridization and Western blotting experiments revealed an increase in delta opioid receptor mRNA and protein levels, respectively, in the dorsal lumbar spinal cord ipsilateral to the CFA injection site compared to the contralateral side and sham-injected controls. By electron microscopy, immunopositive delta opioid receptors were evident in neuronal perikarya, dendrites, unmyelinated axons and axon terminals. Quantification of immunopositive signal in dendrites revealed a twofold increase in the number of immunogold particles in the ipsilateral dorsal spinal cord of CFA-injected rats compared to the contralateral side and to sham-injected rats. Moreover, the relative frequency of immunogold particles associated with or in close proximity to the plasma membrane was increased in the ipsilateral dorsal spinal cord, indicating a more efficient targeting of delta opioid receptors to neuronal plasma membranes. These data demonstrate that CFA induces an up-regulation and increased membrane targeting of delta opioid receptors in the dorsal spinal cord which may account for the enhanced antinociceptive effects of delta opioid receptor agonists in chronic inflammatory pain models.

Immunoelectron microscopic detection of tissue ganglioside antigens.

Glycolipid antigens are emerging as important markers of differentiated cells in vitro and in vivo. The study of the expression of these antigens in whole tissues by immunoelectron microscopy, using standard techniques, does not give acceptable results. We have established conditions for the specific demonstration of antibody binding to tissue glycolipid antigens by immunoelectron microscopy. Dehydration of tissues with alcohol is to be avoided as it extracts the glycolipid antigen out of the tissue. Dehydration in acetone provides good results. Embedding of the tissue in Araldite 512 results in high non-specific binding of the primary antibody and a decreased effective titre of the primary antibody. Embedding of tissues in Lowicryl HM20 resin resulted in low non-specific binding. We also describe a method of curing the Lowicryl resin that does not require a purpose built curing chamber. Quantitative analysis of immunogold binding reveals that acetone dehydration of tissues and embedding in Lowicryl gives greatly superior results in comparison with dehydration in alcohol and embedding in Araldite.

The appreciation of visual jokes in people with schizophrenia: a study of 'mentalizing' ability.

It has been suggested that certain characteristic symptoms of schizophrenia reflect a specific deficit in the ability to attribute mental states to others ('mentalizing'). Patients with negative features, particularly social withdrawal and blunted affect, those with thought disorder and patients with paranoid symptoms have difficulties when they try to infer what is going on in the minds of other people. This study examines this notion using two sets of cartoon jokes. While the first set can be understood purely using physical and semantic analysis, the second set requires that the viewer appreciates the mental state of the main character in order to 'get' the joke. For control subjects there was no difference in the ability to understand the two types of joke, while the schizophrenic patients found the mental state jokes significantly more difficult to understand. This effect was most marked in patients with behavioural disorders and those reporting passivity experiences. Those with paranoid delusions also showed a selective comprehension deficit with the mental state stimuli. Patients who were symptom free at the time of testing showed normal performance.

Sterile water used for humidification in low-flow oxygen therapy: it is necessary?

Currently it is standard practice in many acute care hospitals to use only sterile water in humidifier reservoirs for the delivery of low-flow oxygen therapy. This practice is based primarily on the Centers for Disease Control's 1982 "Guideline for the Prevention of Nosocomial Pneumonia." The present study was designed to investigate and compare the bacterial contamination of tap water and sterile water used to fill clean (nonsterile) disposable oxygen humidifier reservoirs. Disposable oxygen humidification reservoirs were assembled weekly according to standard protocol and regulated to deliver oxygen, 4 to 6 L/min, continuously for 5 consecutive days. Each of 48 reservoirs was filled with either tap water (24) or sterile water (24) and cultured daily. All disposable equipment was discarded after the final culture on the fifth day. An aliquot of water was obtained daily from each reservoir and plated to trypticase soy agar pour plates and to a matched trypticase soy broth. Bacterial growth was observed on trypticase soy agar pour plates from 54 (45.0%) of 120 sterile water reservoir cultures and from 38 (31.7%) of 120 tap water reservoir cultures (p greater than 0.05). Bacterial growth from the matched trypticase soy broth cultures was observed only from two sterile water reservoirs. The microorganisms identified from the sterile water reservoirs included Enterobacter agglomerans and Serratia and Bacillus spp. The use of tap water for low-flow oxygen humidification was determined to be safe at our hospital by the infection control committee. This procedural change contributed approximately $6000 to the cost reduction efforts of the respiratory therapy department.