GPCR modulation by RAMPs

Our conceptual understanding of the molecular architecture of G-protein coupled receptors (GPCRs) has transformed over the last decade. Once considered as largely independent functional units (aside from their interaction with the G-protein itself), it is now clear that a single GPCR is but part of a multifaceted signaling complex, each component providing an additional layer of sophistication. Receptor activity-modifying proteins (RAMPs) provide a notable example of proteins that interact with GPCRs to modify their function. They act as pharmacological switches, modifying GPCR pharmacology for a particular subset of receptors. However, there is accumulating evidence that these ubiquitous proteins have a broader role, regulating signaling and receptor trafficking. This article aims to provide the reader with a comprehensive appraisal of RAMP literature and perhaps some insight into the impact that their discovery has had on those who study GPCRs.     

Prevention of cryoprecipitation during cardiopulmonary bypass in a patient with HIV-HCV co-infections

BACKGROUND: There are no guidelines for the management of patients with cryoglobulins during cardiopulmonary bypass (CPB) necessitating core hypothermia. OBJECTIVE: To evaluate a simple, pragmatic protocol of in vitro temperature-dependent cryoprecipitation of serum in patients with cryoglobulinemia before elective cardiac surgery with CPB. METHODS: A 44-year-old female patient was known for chronic hepatitis C and type III cryoglobulinemia. Elective surgery was planned for an aortic arch aneurysm. A differential serum cryoprecipitation profile was established in vitro prior to surgery. RESULTS: Whereas, at temperatures < or = 15 degrees C, cryoglobulin levels were > or = 0.112 g/L (normal value < 0.05 g/L), at 20 degrees C and above, the precipitate was < or = 0.016 g/L. Accordingly, surgery was performed without any cryoglobulin-related complications at an extracorporeal circulation temperature of 22-24 degrees C, to minimise the risk of cryoprecipitation. CONCLUSION: In elective cases of surgery with CPB and hypothermia, temperature-dependent differential serum cryoprecipitation profile may be an easy and efficient way to assess a safe peroperative level of temperature to avoid complications due to cryoglobulins, without enhancing the patient's tissue ischemia risks.     

EEG/(f)MRI measurements at 7 Tesla using a new EEG cap ("InkCap")

We aimed at improving the signal-to-noise ratio (SNR) of electroencephalography (EEG) during magnetic resonance imaging (MRI) by introducing a new EEG cap ("InkCap") based on conductive ink technology. The InkCap was tested with temperature measurements on an electrically conductive phantom head and during structural and functional MRI (fMRI) recordings in 11 healthy human volunteers at 7 T. Combined EEG/fMRI measurements were conducted to study the interaction between the two modalities. The EEG recordings with the InkCap demonstrated up to a five-fold average decrease in signal variance during echo-planar imaging, with respect to a cap made of standard carbon fiber leads. During concurrent EEG/fMRI measurements in human volunteers, alpha oscillations were clearly detected at 7 T. Minimal artifacts were present in the T2* and high-resolution structural MR images of the brain parenchyma. Our results show that the InkCap technology considerably improves the quality of both EEG and (f)MRI during concurrent measurements even at 7 T.     

Gene expression profile of human airway epithelium induced by hyperoxia in vivo

Hyperoxia leads to oxidative modification and damage of macromolecules in the respiratory tract with loss of biological functions. Given the lack of antioxidant gene induction with acute exposure to 100% oxygen, we hypothesized that clearance pathways for oxidatively modified proteins may be induced and serve in the immediate cellular response to preserve the epithelial layer. To test this, airway epithelial cells were obtained from individuals under ambient oxygen conditions and after breathing 100% oxygen for 12 h. Gene expression profiling identified induction of genes in the chaperone and proteasome-ubiquitin-conjugation pathways that together comprise an integrated cellular response to manage and degrade damaged proteins. Analyses also revealed gene expression changes associated with oxidoreductase function, cell cycle regulation, and ATP synthesis. Increased HSP70, protein ubiquitination, and intracellular ATP were validated in cells exposed to hyperoxia in vitro. Inhibition of proteasomal degradation revealed the importance of accelerated protein catabolism for energy production of cells exposed to hyperoxia. Thus, the human airway early response to hyperoxia relies predominantly upon induction of cytoprotective chaperones and the ubiquitin-proteasome-dependent protein degradation system to maintain airway homeostatic integrity.     

Caries-preventive potential of an adhesive patch after thermomechanical loading--a microbial-based in vitro study

PURPOSE: To assess the enamel-protective potential of a newly devised adhesive patch for smooth enamel sealing. MATERIALS AND METHODS: Approximal surfaces of 30 extracted molars were divided into three areas: the buccal thirds were treated with a flowable composite (Tetric Flow, Ivoclar Vivadent) and served as negative control sites, the lingual thirds were left untreated and served as positive control sites, and the middle thirds served as the test areas. This was sealed with either 1. a twofold application of an unfilled resin (Heliobond, Ivoclar Vivadent), 2. an adhesive prototype patch (Ivoclar Vivadent), or 3. an adhesive patch in combination with a flowable composite. After thermomechanical loading and demineralization in a microbial-based artificial caries chamber, demineralization depth was assessed using a confocal laser scanning microscope. RESULTS: Negative control sites treated with the flowable composite showed no signs of demineralization. Areas treated with the patch showed no signs of demineralization, irrespective of whether it was used in combination with a flowable composite or directly bonded to the enamel. Caries-like lesions in untreated sites showed a mean depth of 134.3 +/- 35.9 microm. Demineralization depth at sites treated with the unfilled resin was 76.2 +/- 26.5 microm (p = 0.023). CONCLUSIONS: Under the conditions of the present study, the adhesive patch under investigation completely protected the underlying enamel from demineralization. This merits further study to assess its potential as an interproximal sealant.     

Reducing Oral Health Disparities: A Focus on Social and Cultural Determinants

Oral health is essential to the general health and well-being of individuals and the population. Yet significant oral health disparities persist in the U.S. population because of a web of influences that include complex cultural and social processes that affect both oral health and access to effective dental health care. This paper introduces an organizing framework for addressing oral health disparities. We present and discuss how the multiple influences on oral health and oral health disparities operate using this framework. Interventions targeted at different causal pathways bring new directions and implications for research and policy in reducing oral health disparities.     

Desmoplastic fibroma of the jaw: a case report and review of literature

Desmoplastic fibroma is a benign intraosseous neoplasm that is recognized as the intraosseous counterpart of soft tissue fibromatosis in both gnathic and extragnathic sites. It has a propensity for locally aggressive behavior and local recurrence. In the present report, we define the clinicopathological and radiographic features of a desmoplastic fibroma of the mandible in an 8-year-old white boy who initially presented with a 2-month history of a rapidly expanding, painless mass along the right inferior border of his mandible. A critical and comprehensive review of the English language literature is also provided.     

Critical elements of spirituality as identified by adolescent mental health clients

BACKGROUND: Client spirituality has been recognized as a central component of Canadian occupational therapy, but little research has been conducted in this area. PURPOSE: This exploratory study attempted to gain insight into the relevant elements of spirituality and its importance to inpatient adolescent mental health clients. METHOD: An adolescent spirituality questionnaire was developed from definitions of spirituality in the literature, modified by a focus group consisting of members of the target population, and administered to 11 respondents. RESULTS: Elements related to the individual and lifelong pursuits of the individual were most closely associated with spirituality while those items traditionally connected with spirituality and with external pursuits, activities, and relationships are considered less relevant by this population. Results suggest that spirituality is important to a majority of inpatient adolescent mental health clients. PRACTICE IMPLICATIONS: It is suggested that more studies drawing information on spirituality directly from specific client populations are essential for the occupational therapy community to improve its comprehension of, and to better its ability to address in practice, the critical area of client spirituality.     

The art of public health nursing: using confession technè in the sexual health domain

AIM: This paper explores the sexual health interview from a critical perspective, and to demonstrate how the confession ritual involved in this interview is implicated in the construction of subjectivities (meaning identities) as well as in fostering self-surveillance (self-regulation). BACKGROUND: The concept of public health depends primarily on several surveillance tools that monitor both the incidence and prevalence rates of certain diseases. Within the subgroup of infectious diseases, sexually transmitted infections comprise a group that is closely monitored. As a result, surveillance techniques, including policing sexual practices, are part of the public health worker's mandate. METHOD: Using a Foucauldian perspective, we demonstrate that confession is a political technology in the sexual health domain. FINDINGS: As one group of frontline workers in the field of sexual health, nurses are responsible for data collection through methods such as interviewing clients. Nurses play an integral role in the sexual health experience of clients as well as in the construction of the client's subjectivity. We strongly believe that a Foucauldian perspective could be useful in explaining certain current client behavioural trends (for example, an avoidance by at-risk groups of interactions with nurses in sexual health clinics) being observed in sexual health clinics across the Western hemisphere. CONCLUSION: Clinicians need to be aware of the confessional nature of their questions and provide requested services rather than impose services that they determine to be important and relevant. By appreciating that the sexual health interview is an invasive and embarrassing sexual confession, healthcare providers and policy-makers may be better able to design and implement more user-oriented, population-sensitive sexual health services.