A soluble mouse brain splice variant of type 2alpha corticotropin-releasing factor (CRF) receptor binds ligands and modulates their activity

Peptides of the corticotropin-releasing factor (CRF) family signal through the activation of two receptors, CRF receptor type 1 (CRFR1) and type 2 (CRFR2), both of which exist as multiple splice variants. We have identified a cDNA from mouse brain encoding a splice variant, soluble CRFR2alpha (sCRFR2alpha), in which exon 6 is deleted from the gene encoding CRFR2alpha. Translation of this isoform produces a predicted 143-aa soluble protein. The translated protein includes a majority of the first extracellular domain of the CRFR2alpha followed by a unique 38-aa hydrophilic C terminus resulting from a frame shift produced by deletion of exon 6. By using RT-PCR and Southern hybridization, the relative mRNA expression levels of full-length (seven transmembrane domains) CRFR2alpha and the soluble form (sCRFR2alpha) in the mouse brain were measured with a single reaction. The results demonstrate high levels of expression of sCRFR2alpha in the olfactory bulb, cortex, and midbrain regions. A rabbit antiserum raised against a synthetic peptide fragment encoding the unique C terminus revealed specific sCRFR2alpha immunoreactivity in mouse brain slices by immunohistochemistry and in extracts of brain regions by RIA. Interestingly, the sCRFR2alpha immunoreactivity distribution closely approximated that of CRFR1 expression in rodent brain. A protein corresponding to sCRFR2alpha, expressed and purified from either mammalian or bacterial cell systems, binds several CRF family ligands with low nanomolar affinities. Furthermore, the purified sCRFR2alpha protein inhibits cellular responses to CRF and urocortin 1. These data support a potential role of the sCRFR2alpha protein as a possible biological modulator of CRF family ligands.     

Bedside ultrasonography: Applications in critical care: Part I

There is increasing interest in the use of ultrasound to assess and guide the management of critically ill patients. The ability to carry out quick examinations by the bedside to answer specific clinical queries as well as repeatability are clear advantages in an acute care setting. In addition, delays associated with transfer of patients out of the Intensive Care Unit (ICU) and exposure to ionizing radiation may also be avoided. Ultrasonographic imaging looks set to evolve and complement clinical examination of acutely ill patients, offering quick answers by the bedside. In this two-part narrative review, we describe the applications of ultrasonography with a special focus on the management of the critically ill. Part I explores the utility of echocardiography in the ICU, with emphasis on its usefulness in the management of hemodynamically unstable patients. We also discuss lung ultrasonography - a vastly underutilized technology for several years, until intensivists began to realize its usefulness, and obvious advantages over chest radiography. Ultrasonography is rapidly emerging as an important tool in the hands of intensive care physicians.     

Impact of routine angiographic follow-up after percutaneous coronary intervention with drug-eluting stents in the SPIRIT III randomized trial at three years

Routine angiographic follow-up after bare-metal stent implantation has been associated with an increase in coronary revascularization. The impact of angiographic follow-up after drug-eluting stent placement remains poorly characterized. The prospective, randomized, single-blinded SPIRIT III trial assigned patients to the everolimus-eluting stent or the paclitaxel-eluting stent (PES). Major adverse cardiovascular events (cardiac death, myocardial infarction, and ischemia-driven target lesion revascularization [ID-TLR]) at 3 years were assessed by angiographic versus clinical-only follow-up at 8 months ± 28 days and a landmark survival analysis from 9 months to 3 years. Of 1,002 patients, 564 patients were assigned to angiographic follow-up at 8 months ± 28 days and 438 patients underwent clinical follow-up alone. Three-year major adverse cardiovascular event rates were 10.6% in the angiographic group and 12.0% in the clinical follow-up group (p = 0.64). Ischemia-driven revascularization increased twofold at 9 months, but no difference was noted in ID-TLR for either device. Non-ID-TLR was significantly higher in patients in the angiographic group (4.5% vs 1.0%, p = 0.002), a difference resulting from PES (9.1% vs 0.7%, p = 0.0007) rather than everolimus-eluting stent (2.2% vs 1.1%, p = 0.36) treatment. The landmark analysis showed no significant differences between the angiographic and clinical follow-up groups from 9 months to 3 years of major clinical outcomes. In conclusion, routine angiographic follow-up in SPIRIT III did not increase rates of ID-TLR compared to clinical follow-up alone. Despite higher nonischemia-driven revascularization rates with angiographic follow-up of patients with PESs, none of the safety end points were adversely affected.     

Are procedures performed by dental auxiliaries safe and of comparable quality? A systematic review

The objective of the current study was to systematically evaluate the existing evidence in relation to the safety, quality, productivity or cost-benefit, and patient satisfaction of the procedures performed by the different groups of dental providers. Due to the diversity of the procedures performed and the outcomes measured, it was not possible to create pooled estimates in a meaningful manner. Therefore, summary results of individual studies are presented and critically evaluated.     

Weight Recidivism Post-Bariatric Surgery: A Systematic Review

Obesity is considered a worldwide health problem of epidemic proportions. Bariatric surgery remains the most effective treatment for patients with severe obesity, resulting in improved obesity-related co-morbidities and increased overall life expectancy. However, weight recidivism has been observed in a subset of patients post-bariatric surgery. Weight recidivism has significant medical, societal and economic ramifications. Unfortunately, there is a very limited understanding of how to predict which bariatric surgical patients are more likely to regain weight following surgery and how to appropriately treat patients who have regained weight. The objective of this paper is to systematically review the existing literature to assess the incidence and causative factors associated with weight regain following bariatric surgery. An electronic literature search was performed of the Medline, Embase and Cochrane library databases along with the PubMed US national library from January 1950 to December 2012 to identify relevant articles. Following an initial screen of 2,204 titles, 1,437 abstracts were reviewed and 1,421 met exclusion criteria. Sixteen studies were included in this analysis: seven case series, five surveys and four non-randomized controlled trials, with a total of 4,864 patients for analysis. Weight regain in these patients appeared to be multi-factorial and overlapping. Aetiologies were categorized as patient specific (psychiatric, physical inactivity, endocrinopathies/metabolic and dietary non-compliance) and operation specific. Weight regain following bariatric surgery varies according to duration of follow-up and the bariatric surgical procedure performed. The underlying causes leading to weight regain are multi-factorial and related to patient- and procedure-specific factors. Addressing post-surgical weight regain requires a systematic approach to patient assessment focusing on contributory dietary, psychologic, medical and surgical factors.