Perceived need for spiritual and religious treatment options in chronically ill individuals

The objective of the study was to examine the desire for spiritual and religious treatment options in chronically ill adults. Email interview data (N = 12) generated themes for religion, spirituality, and desired treatments. The resultant questionnaire data (N = 83) analysed the popularity of treatments. Thirty-five wide-ranging spiritual and religious treatment options were identified for use in the questionnaire; 47 per cent of the sample was interested in spiritual or religious treatments. There is a need for spiritual and religious treatment options, and translation of treatments into practice would assist coping for many people.     

The effect of maternal smoking and drinking during pregnancy upon (3)H-nicotine receptor brainstem binding in infants dying of the sudden infant death syndrome: initial observations in a high risk population.

The high rate of the sudden infant death syndrome (SIDS) in American Indians in the Northern Plains (3.5/1000) may reflect the high incidence of cigarette smoking and alcohol consumption during pregnancy. Nicotine, a neurotoxic component of cigarettes, and alcohol adversely affect nicotinic receptor binding and subsequent cholinergic development in animals. We measured (3)H-nicotine receptor binding in 16 brainstem nuclei in American Indian SIDS (n = 27) and controls (n = 6). In five nuclei related to cardiorespiratory control, (3)H-nicotinic binding decreased with increasing number of drinks (P < 0.03). There were no differences in binding in SIDS compared with controls, except upon stratification of prenatal exposures. In three mesopontine nuclei critical for arousal there were reductions (P < 0.04) in binding in controls exposed to cigarette smoke compared with controls without exposure; there was no difference between SIDS cases with or without exposure. This study suggests that maternal smoking and alcohol affects (3)H-nicotinic binding in the infant brainstem irrespective of the cause of death. It also suggests that SIDS cases are unable to respond to maternal smoking with the "normal" reduction seen in controls. Future studies are needed to establish the role of adverse prenatal exposures in altered brainstem neurochemistry in SIDS.     

Physiology, pharmacology, and therapeutic potential of protease-activated receptors in vascular disease

It has been 20 years since the discovery of the prototypical protease-activated receptor (PAR). In the time since this landmark work, significant advances have been made in our understanding of this family of four G protein-coupled receptors. Initially discovered and characterized in an attempt to determine the mechanism by which thrombin activates platelets, PARs have since been found to be widely expressed throughout the body, respond to multiple proteases, and to be involved in a vast array of physiological processes. Yet despite their wide-ranging expression, the function of PARs has been most extensively studied in the vascular system. In particular, the importance of PAR1 for platelet activation during arterial thrombosis has been thoroughly investigated and has led to the development of a host of PAR1 antagonists--two of which are currently in Phase 3 trials as antiplatelet agents. Given the impending clinical use of the first PAR antagonists, it is timely to review the physiological roles of PARs in cells of the blood and blood vessels, the development and experimental use of PAR antagonists in these systems, and the potential clinical application of these agents as therapeutics for vascular diseases.     

Expedited computed tomography perfusion and angiography in acute ischemic stroke: a feasibility study

Background

Acute ischemic stroke diagnosis and treatment are among the most challenging in Emergency Medicine. Perfusion computed tomography (CTP) can increase the sensitivity for detecting ischemic stroke and, especially with the addition of CT angiography (CTA), improve decision-making regarding thrombolytic therapy compared to non-contrast computed tomography (NCCT) alone. However, because acute stroke protocols do not generally include procedures for multimodal imaging, they are not commonly performed. In addition, there is concern that additional studies could delay or preclude therapy in patients otherwise eligible for thrombolytic therapy.

Objectives

To demonstrate the feasibility of perfusion CTP and CTA in addition to NCCT of the brain in the emergency assessment of patients with acute ischemic stroke. Methods: Starting January 2008, multimodal (CTP and CTA) imaging was added to NCCT in the Emergency Department (ED) initial assessment of patients with stroke of ≤ 5 h duration. Over the subsequent 9 months, we measured the time from ED arrival to imaging and to recombinant tissue plasminogen activator (rt-PA) treatment and compared these times to patients evaluated with CT alone.

Results

From January to October 2008, 95 patients had CTP and CTA studies in addition to NCCT for acute ischemic stroke. There were no differences between the average time to CT study or to rt-PA treatment between patients evaluated with multimodal CT imaging and patients assessed with NCCT alone.

Conclusions

Combining CTP and CTA with NCCT is feasible and does not adversely increase the time to CT imaging or rt-PA treatment in patients with acute ischemic stroke.     

Slits affect the timely migration of neural crest cells via robo receptor

Background: Neural crest cells emerge by delamination from the dorsal neural tube and give rise to various components of the peripheral nervous system in vertebrate embryos. These cells change from non‐motile into highly motile cells migrating to distant areas before further differentiation. Mechanisms controlling delamination and subsequent migration of neural crest cells are not fully understood. Slit2, a chemorepellant for axonal guidance that repels and stimulates motility of trunk neural crest cells away from the gut has recently been suggested to be a tumor suppressor molecule. The goal of this study was to further investigate the role of Slit2 in trunk neural crest cell migration by constitutive expression in neural crest cells. Results: We found that Slit gain‐of‐function significantly impaired neural crest cell migration while Slit loss‐of‐function favored migration. In addition, we observed that the distribution of key cytoskeletal markers was disrupted in both gain and loss of function instances. Conclusions: These findings suggest that Slit molecules might be involved in the processes that allow neural crest cells to begin migrating and transitioning to a mesenchymal type. Developmental Dynamics 241:1274–1288, 2012. © 2012 Wiley Periodicals, Inc.     

The origin of the stapes and relationship to the otic capsule and oval window

Background: The stapes, an ossicle found within the middle ear, is involved in transmitting sound waves to the inner ear by means of the oval window. There are several developmental problems associated with this ossicle and the oval window, which cause hearing loss. The developmental origin of these tissues has not been fully elucidated. Results: Using transgenic reporter mice, we have shown that the stapes is of dual origin with the stapedial footplate being composed of cells of both neural crest and mesodermal origin. Wnt1cre/Dicer mice fail to develop neural crest‐derived cartilages, therefore, have no middle ear ossicles. We have shown in these mice the mesodermal stapedial footplate fails to form and the oval window is induced but underdeveloped. Conclusions: If the neural crest part of the stapes fails to form the mesodermal part does not develop, indicating that the two parts are interdependent. The stapes develops tightly associated with the otic capsule, however, it is not essential for the positioning of the oval window, suggesting that other tissues, perhaps within the inner ear are needed for oval window placement. Developmental Dynamics 241:1396–1404, 2012. © 2012 Wiley Periodicals, Inc.     

A novel form of chondrocyte stress is triggered by a COMP mutation causing pseudoachondroplasia

Pseudoachondroplasia (PSACH) results from mutations in cartilage oligomeric matrix protein (COMP) and the p.D469del mutation within the type III repeats of COMP accounts for approximately 30% of PSACH. To determine disease mechanisms of PSACH in vivo, we introduced the Comp D469del mutation into the mouse genome. Mutant animals were normal at birth but grew slower than their wild-type littermates and developed short-limb dwarfism. In the growth plates of mutant mice chondrocyte columns were reduced in number and poorly organized, while mutant COMP was retained within the endoplasmic reticulum (ER) of cells. Chondrocyte proliferation was reduced and apoptosis was both increased and spatially dysregulated. Previous studies on COMP mutations have shown mutant COMP is co-localized with chaperone proteins, and we have reported an unfolded protein response (UPR) in mouse models of PSACH-MED (multiple epiphyseal dysplasia) harboring mutations in Comp (T585M) and Matn3, Comp etc (V194D). However, we found no evidence of UPR in this mouse model of PSACH. In contrast, microarray analysis identified expression changes in groups of genes implicated in oxidative stress, cell cycle regulation, and apoptosis, which is consistent with the chondrocyte pathology. Overall, these data suggest that a novel form of chondrocyte stress triggered by the expression of mutant COMP is central to the pathogenesis of PSACH.