Planning for psychiatric emergencies.

Hospital emergency services have been used increasingly in recent years. This has resulted in questions as to the true nature of patients'' complaints and the appropriateness of this type of care. Since the increase in the number of psychiatric emergency patients has paralleled that for patients at other types of emergency clinics a study was conducted at the Clarke Institute of Psychiatry, Toronto, to examine the situation prior to the inception in 1977 of a crisis intervention unit. It was found that most patients had both psychiatric and social difficulties, and it was considered that planning should concentrate on strategies for efficient management of the clinical problems.     

Effect of the velopharynx on intraluminal pressures in reconstructed pharynges derived from individuals with and without sleep apnea

The most collapsible part of the upper airway in the majority of individuals is the velopharynx which is the segment positioned behind the soft palate. As such it is an important morphological region for consideration in elucidating the pathogenesis of obstructive sleep apnea (OSA). This study compared steady flow properties during inspiration in the pharynges of nine male subjects with OSA and nine body-mass index (BMI)- and age-matched control male subjects without OSA. The k  –ω$\omega$SST turbulence model was used to simulate the flow field in subject-specific pharyngeal geometric models reconstructed from anatomical optical coherence tomography (aOCT) data. While analysis of the geometry of reconstructed pharynges revealed narrowing at velopharyngeal level in subjects with OSA, it was not possible to clearly distinguish them from subjects without OSA on the basis of pharyngeal size and shape alone. By contrast, flow simulations demonstrated that pressure fields within the narrowed airway segments were sensitive to small differences in geometry and could lead to significantly different intraluminal pressure characteristics between subjects. The ratio between velopharyngeal and total pharyngeal pressure drops emerged as a relevant flow-based criterion by which subjects with OSA could be differentiated from those without.     

Metarhizium anisopliae Pathogenesis of Mosquito Larvae: A Verdict of Accidental Death

Metarhizium anisopliae, a fungal pathogen of terrestrial arthropods, kills the aquatic larvae of Aedes aegypti, the vector of dengue and yellow fever. The fungus kills without adhering to the host cuticle. Ingested conidia also fail to germinate and are expelled in fecal pellets. This study investigates the mechanism by which this fungus adapted to terrestrial hosts kills aquatic mosquito larvae. Genes associated with the M. anisopliae early pathogenic response (proteinases Pr1 and Pr2, and adhesins, Mad1 and Mad2) are upregulated in the presence of larvae, but the established infection process observed in terrestrial hosts does not progress and insecticidal destruxins were not detected. Protease inhibitors reduce larval mortality indicating the importance of proteases in the host interaction. The Ae. aegypti immune response to M. anisopliae appears limited, whilst the oxidative stress response gene encoding for thiol peroxidase is upregulated. Cecropin and Hsp70 genes are downregulated as larval death occurs, and insect mortality appears to be linked to autolysis through caspase activity regulated by Hsp70 and inhibited, in infected larvae, by protease inhibitors. Evidence is presented that a traditional host-pathogen response does not occur as the species have not evolved to interact. M. anisopliae retains pre-formed pathogenic determinants which mediate host mortality, but unlike true aquatic fungal pathogens, does not recognise and colonise the larval host.     

Indolin-2-one p38α inhibitors III: bioisosteric amide replacement

Crystallographic structural information was used in the design and synthesis of a number of bioisosteric derivatives to replace the amide moiety in a lead series of p38α inhibitors which showed general hydrolytic instability in human liver preparations. Triazole derivative 13 was found to have moderate bioavailability in the rat and demonstrated potent in-vivo activity in an acute model of inflammation.     

Photoperiod and Vernalization Responses in Triticum turgidumxT. tauschii Synthetic Hexaploid Wheats

Studies of synthetic hexaploid wheat developed from Triticumturgidum(AABB genomes) and T. tauschii(DD genome) can provideinformation on potentially useful characters in T. tauschiiand/or T. turgidum for genetic improvement of hexaploid wheat(T. aestivum). Synthetic hexaploid wheats and the T. turgidumand T. tauschii parents were assessed for their developmentalresponses to photoperiod and vernalization for days to ear emergence,final leaf number and the number of spikelets per spike. Theresponses to photoperiod and vernalization of the synthetichexaploids were generally intermediate between those of theparents but in some instances the levels of expression exhibitedby the T. tauschii or T. turgidum parents were epistatic inthe synthetic hexaploids. The relatively strong photoperiodresponse of the T. tauschii accessions was not expressed inthe synthetic hexaploids, but rather the synthetic hexaploidsreflected the photoperiod response of the respective T. turgidumparents. The synthetic hexaploids had vernalization responsesstronger than those of the T. turgidum and bread wheats usedin the study. The expression of ear emergence in response tovernalization of these synthetic hexaploids appeared to be modifiedby the T. turgidum parent. Copyright 2001 Annals of Botany Company Photoperiod, synthetic hexaploids, Triticum aestivum, Triticum tauschii, Triticum turgidum, vernalization     

The impact of continuous positive airway pressure on the lower esophageal sphincter

The lower esophageal sphincter (LES) is the primary barrier to gastroesophageal reflux. Reflux is associated with periods of LES relaxation, as occurs during swallowing. Continuous positive airway pressure (CPAP) has been shown to reduce reflux in individuals with and without sleep apnea, by an unknown mechanism. The aim of this study was to determine the effect of CPAP on swallow-induced LES relaxation. Measurements were made in 10 healthy, awake, supine individuals. Esophageal (Pes), LES (Ples), gastric (Pg), and barrier pressure to reflux (Pb = Ples - Pg) were recorded using a sleeve catheter during five swallows of 5 ml of water. This was repeated at four levels of CPAP (0, 5, 10, and 15 cmH(2)O). Pressures were measured during quiet breathing and during the LES relaxation associated with a swallow. Duration of LES relaxation was also recorded. During quiet breathing, CPAP significantly increased end-expiratory Pes, Ples, Pg, and Pb (P < 0.05). The increase in Pb was due to a disproportionate increase in Ples compared with Pg (P < 0.05). During a swallow, CPAP increased nadir Ples, Pg, and Pb and decreased the duration of LES relaxation (4.1 s with 0-cmH(2)O CPAP to 1.6 s on 15-cmH(2)O CPAP, P < 0.001). Pb increased with CPAP by virtue of a disproportionate increase in Ples compared with Pg. This may be due to either reflex activation of LES smooth muscle, or nonspecific transmission of pressure to the LES. The findings suggest CPAP may make the LES less susceptible to reflux by increasing Pb and decreasing the duration of LES relaxation.     

Calcium block of single sodium channels: role of a pore-lining aromatic residue

Extracellular Ca(2+) ions cause a rapid block of voltage-gated sodium channels, manifest as an apparent reduction of the amplitude of single-channel currents. We examined the influence of residue Tyr-401 in the isoform rNa(V)1.4 on both single-channel conductance and Ca(2+) block. An aromatic residue at this position in the outer mouth of the pore plays a critical role in high-affinity block by the guanidinium toxin tetrodotoxin, primarily due to an electrostatic attraction between the cationic blocker and the system of pi electrons on the aromatic face. We tested whether a similar attraction between small metal cations (Na(+) and Ca(2+)) and this residue would enhance single-channel conductance or pore block, using a series of fluorinated derivatives of phenylalanine at this position. Our results show a monotonic decrease in Ca(2+) block as the aromatic ring is increasingly fluorinated, a result in accord with a cation-pi interaction between Ca(2+) and the aromatic ring. This occurred without a change of single-channel conductance, consistent with a greater electrostatic effect of the pi system on divalent than on monovalent cations. High-level quantum mechanical calculations show that Ca(2+) ions likely do not bind directly to the aromatic ring because of the substantial energetic penalty of dehydrating a Ca(2+) ion. However, the complex of a Ca(2+) ion with its inner hydration shell, Ca(2+)(H(2)O)(6), interacts electrostatically with the aromatic ring in a way that affects the local concentration of Ca(2+) ions in the extracellular vestibule.