No Clinic Left Behind: Providing Cost-Effective In-Services Via Distance Learning

Journal for Healthcare Quality : Official Publication of the National Association for Healthcare Quality. Nov, 2010  |  Pubmed ID: 22059939

Based on the successful pilot implementation of a Veterans Affairs Quality Enhancement Research Initiative (QUERI) aimed at increasing HIV testing throughout four local facilities and their associated satellite clinics, we expanded our efforts to deploy our methods to substantially more sites spanning six states. Our goal was to implement and examine the cost effectiveness of a distance-learning model to offer provider education to geographically remote (sub)facilities. We developed and implemented an equivalent interactive online version of our in-person presentation. Handouts were shipped to each site before the day of the in-service. Remote participants were receptive to this cost-effective form of provider activation. The technology functioned dependably; no presentation anomalies were encountered. Participants rated in-person presentations higher than online, however, mean scores for both methods were >80%. Online presentations were found to be considerably more affordable than in-person. These findings suggest that this alternate approach may offer a feasible alternative for a variety of subjects.

Oncolytic Poliovirus Against Malignant Glioma

Future Virology. Sep, 2011  |  Pubmed ID: 21984883

In cancerous cells, physiologically tight regulation of protein synthesis is lost, contributing to uncontrolled growth and proliferation. We describe a novel experimental cancer therapy approach based on genetically recombinant poliovirus that targets an intriguing aberration of translation control in malignancy. This strategy is based on the confluence of several factors enabling specific and efficacious cancer cell targeting. Poliovirus naturally targets the vast majority of ectodermal/neuroectodermal cancers expressing its cellular receptor. Evidence from glioblastoma patients suggests that the poliovirus receptor is ectopically upregulated on tumor cells and may be associated with stem cell-like cancer cell populations and proliferating tumor vasculature. We exploit poliovirus' reliance on an unorthodox mechanism of protein synthesis initiation to selectively drive viral translation, propagation and cytotoxicity in glioblastoma. PVSRIPO, a prototype nonpathogenic poliovirus recombinant, is scheduled to enter clinical investigation against glioblastoma.

Effects of Different Lipopolysaccharide Preparations on Neutrophil Function in the Fathead Minnow, Pimephales Promelas Rafinesque

Journal of Fish Diseases. Nov, 2011  |  Pubmed ID: 21988359

The Russians at Haslar 1808/9. The Admission of Russian Military to the Royal Hospital Haslar from November 1808 to August 1809

Journal of the Royal Naval Medical Service. 2011  |  Pubmed ID: 22013642

Mechanical Behavior of Carpal Tunnel Subsynovial Connective Tissue Under Compression

The Iowa Orthopaedic Journal. 2011  |  Pubmed ID: 22096431

Subsynovial connective tissue (SSCT) is a fluid-permeated loose connective tissue that occupies the majority of the space in the carpal tunnel not occupied by the digital flexor tendons or the median nerve. It is arranged in layers around these more discrete structures, presumably to assist with tendon gliding. As a result of this arrangement, the compressive behavior and the fluid permeability of this tissue may substantially affect the stresses in the median nerve resulting from contact with its neighboring tendons or with the walls of the tunnel itself. These stresses may contribute to damage of the median nerve and the development of carpal tunnel syndrome. In this study, the fluid permeability and the compressive behavior of the SSCT were investigated to better understand the mechanics of this tissue and how it may mediate mechanical insult to the median nerve. A custom experimental apparatus was built to allow simultaneous measurement of tissue compression and fluid flow. Using Darcy's law, the average SSCT fluid permeability was 8.78×10(15) m(4)/Ns. The compressive behavior of the SSCT demonstrated time dependence, with an initial modulus of 395kPa gradually decreasing to a value of 285kPa. These baseline tissue data may serve as a mechanical norm (toward which pathological tissue might be returned, therapeutically) and may serve as essential properties to include in future mechanical models of the carpal tunnel.

Colonoscopic Surveillance in Inflammatory Bowel Disease: State of the Art Reduction of Biopsies

Digestive Diseases (Basel, Switzerland). 2011  |  Pubmed ID: 22104751

Longstanding colitis in inflammatory bowel disease (IBD) is associated with an increased risk for intraepithelial neoplasia (IN). White light endoscopy (WLE) with 40-50 random biopsies has been promoted for surveillance but may miss a significant proportion of lesions. In addition, the yield of random biopsies to detect IN is low, and random biopsies are expensive, labor-intensive and distract from scrutinizing the colon. Chromoendoscopy with targeted biopsies has proven its superiority over WLE in multiple randomized trials. It has been incorporated into many national and international guidelines. Virtual chromoendoscopy techniques carry the potential to provide contrast enhancement without spraying color onto the mucosa. However, trials using virtual chromoendoscopy techniques have failed to show enhanced detection of IN compared to WLE so far. Autofluorescence imaging has the potential to serve as a red-flag technique for macroscopic detection of IN by screening large mucosal areas in IBD. Confocal laser endomicroscopy (CLE) is able to provide intravital microscopic diagnosis on a cellular level. In a first study, CLE had a high accuracy for prediction of neoplasia. Together, all these modern endoscopy approaches aim at overcoming shortcomings of WLE in a move towards abandoning untargeted random biopsies for targeted, 'smart' biopsies. Future efforts to optimize endoscopic surveillance in inflammatory colitis should aim at identifying patients at high risk of developing IN, tailor individual surveillance intervals, use red-flag techniques for IN detection and may even predict response to tailored therapy.

Magnetic Resonance Imaging Monsters and Surgical Vampires

Archives of Surgery (Chicago, Ill. : 1960). Nov, 2011  |  Pubmed ID: 22106330

Patient Characteristics Associated with HCV Treatment Adherence, Treatment Completion, and Sustained Virologic Response in HIV Coinfected Patients

AIDS Research and Treatment. 2011  |  Pubmed ID: 22110904

Background. Hepatitis C (HCV) treatment efficacy among HIV patients is limited by poor treatment adherence and tolerance, but few studies have examined the psychosocial determinants of treatment adherence and outcomes. Methods. Chart abstracted and survey data were collected on 72 HIV patients who had received pegylated interferon and ribavirin to assess correlates of treatment adherence, completion, and sustained virologic response (SVR). Results. Nearly half (46%) the sample had active psychiatric problems and 13% had illicit drug use at treatment onset; 28% reported <100% treatment adherence, 38% did not complete treatment (mostly due to virologic nonresponse), and intent to treat SVR rate was 49%. Having a psychiatric diagnosis was associated with nonadherence, while better HCV adherence was associated with both treatment completion and SVR. Conclusions. Good mental health may be an indicator of HCV treatment adherence readiness, which is in turn associated with treatment completion and response, but further research is needed with new HCV treatments emerging.

Local Barrier Dysfunction Identified by Confocal Laser Endomicroscopy Predicts Relapse in Inflammatory Bowel Disease

Gut. Nov, 2011  |  Pubmed ID: 22115910

ObjectivesLoss of intestinal barrier function plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Shedding of intestinal epithelial cells is a potential cause of barrier loss during inflammation. The objectives of the study were (1) to determine whether cell shedding and barrier loss in humans can be detected by confocal endomicroscopy and (2) whether these parameters predict relapse of IBD.MethodsConfocal endomicroscopy was performed in IBD and control patients using intravenous fluorescein to determine the relationship between cell shedding and local barrier dysfunction. A grading system based on appearances at confocal endomicroscopy in humans was devised and used to predict relapse in a prospective pilot study of 47 patients with ulcerative colitis and 11 patients with Crohn's disease.ResultsConfocal endomicroscopy in humans detected shedding epithelial cells and local barrier defects as plumes of fluorescein effluxing through the epithelium. Mouse experiments demonstrated inward flow through some leakage-associated shedding events, which was increased when luminal osmolarity was decreased. In IBD patients in clinical remission, increased cell shedding with fluorescein leakage was associated with subsequent relapse within 12 months after endomicroscopic examination (p<0.001). The sensitivity, specificity and accuracy for the grading system to predict a flare were 62.5% (95% CI 40.8% to 80.4%), 91.2% (95% CI 75.2 to 97.7) and 79% (95% CI 57.7 to 95.5), respectively.ConclusionsCell shedding and barrier loss detected by confocal endomicroscopy predicts relapse of IBD and has potential as a diagnostic tool for the management of the disease.

Hemodynamic Effects of Orally Administered Delta-ALA During Radical Prostatectomy

World Journal of Urology. Nov, 2011  |  Pubmed ID: 22120180

PURPOSE: We investigated hemodynamics in patients receiving delta-Aminolevulinic acid (delta-ALA) to visualize tumor margins prior to radical retro pubic prostatectomy. PATIENTS: Twenty patients undergoing elective open radical retro pubic prostatectomy (RRP). METHODS: Cohort observational study. Ten patients receiving 20 mg/kg of delta-ALA orally prior to surgery (delta-ALA) and 10 patients undergoing RRP without the application of delta-ALA served as a retrospectively matched cohort (CONTROL). MEASUREMENTS: Changes in heart rate (HR), mean arterial blood pressure (MAP), and functional hemodynamic parameters were assessed by electrocardiogram, non-invasive and invasive blood pressure monitoring plus transcardiopulmonary thermodilution. RESULTS: Patients of both groups did not differ in means of age, body mass index, or ASA classification. During surgery, HR and MAP did not differ significantly between both groups. Also, the amount of IV crystalloids and colloids did not differ significantly. In contrast, the amount of vasopressor necessary to maintain MAP within the target range of 70-90 mmHg was significantly higher in delta-ALA when compared to CONTROL (0.08 ± 0.04 μg/kg/min (delta-ALA) vs. 0.03 ± 0.02 μg/kg/min (CONTROL); P < 0.01). Immediately after surgery, patients of delta-ALA showed a significantly higher heart rate (82 ± 18 min(-1) vs. 67 ± 9 min(-1); P < 0.05) compared to patients of CONTROL. Cardiac index, global end-diastolic volume index, and extravascular lung water index were significantly higher after surgery, when compared to baseline values (P < 0.05). CONCLUSIONS: Orally administered delta-ALA prior to open radical prostatectomy induces hemodynamic instability in the perioperative period requiring vasopressor support. Further, an increase of extravascular lung water points toward an increased vascular permeability induced by delta-ALA.

[Caveolin-1 Forces Matrix Remodeling]

Médecine Sciences : M/S. Nov, 2011  |  Pubmed ID: 22130020

Automated Discovery of Drug Treatment Patterns for Endocrine Therapy of Breast Cancer Within an Electronic Medical Record

Journal of the American Medical Informatics Association : JAMIA. Dec, 2011  |  Pubmed ID: 22140207

ObjectiveTo develop an algorithm for the discovery of drug treatment patterns for endocrine breast cancer therapy within an electronic medical record and to test the hypothesis that information extracted using it is comparable to the information found by traditional methods.MaterialsThe electronic medical charts of 1507 patients diagnosed with histologically confirmed primary invasive breast cancer.MethodsThe automatic drug treatment classification tool consisted of components for: (1) extraction of drug treatment-relevant information from clinical narratives using natural language processing (clinical Text Analysis and Knowledge Extraction System); (2) extraction of drug treatment data from an electronic prescribing system; (3) merging information to create a patient treatment timeline; and (4) final classification logic.ResultsAgreement between results from the algorithm and from a nurse abstractor is measured for categories: (0) no tamoxifen or aromatase inhibitor (AI) treatment; (1) tamoxifen only; (2) AI only; (3) tamoxifen before AI; (4) AI before tamoxifen; (5) multiple AIs and tamoxifen cycles in no specific order; and (6) no specific treatment dates. Specificity (all categories): 96.14%-100%; sensitivity (categories (0)-(4)): 90.27%-99.83%; sensitivity (categories (5)-(6)): 0-23.53%; positive predictive values: 80%-97.38%; negative predictive values: 96.91%-99.93%.DiscussionOur approach illustrates a secondary use of the electronic medical record. The main challenge is event temporality.ConclusionWe present an algorithm for automated treatment classification within an electronic medical record to combine information extracted through natural language processing with that extracted from structured databases. The algorithm has high specificity for all categories, high sensitivity for five categories, and low sensitivity for two categories.

Renal Cell Carcinoma Presenting As a Tongue Lesion

Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. Sep, 2011  |  Pubmed ID: 21940088

Gentrification in Black and White: the Racial Impact of Public Housing Demolition in American Cities

Urban Studies (Edinburgh, Scotland). 2011  |  Pubmed ID: 21949948

The gentrification that has transformed high-poverty neighbourhoods in US cities since the mid 1990s has been characterised by high levels of state reinvestment. Prominent among public-sector interventions has been the demolition of public housing and in some cases multimillion dollar redevelopment efforts. In this paper, the racial dimension of state-supported gentrification in large US cities is examined by looking at the direct and indirect displacement induced by public housing transformation. The data show a clear tendency towards the demolition of public housing projects with disproportionately high African American occupancy. The pattern of indirect displacement is more varied; public housing transformation has produced a number of paths of neighbourhood change. The most common, however, involve significant reductions in poverty, sometimes associated with Black to White racial turnover and sometimes not. The findings underscore the central importance of race in understanding the dynamics of gentrification in US cities.

Transmembrane Gate Movements in the Type II ATP-binding Cassette (ABC) Importer BtuCD-F During Nucleotide Cycle

The Journal of Biological Chemistry. Nov, 2011  |  Pubmed ID: 21953468

ATP-binding cassette (ABC) transporters are ubiquitous integral membrane proteins that translocate substrates across cell membranes. The alternating access of their transmembrane domains to opposite sides of the membrane powered by the closure and reopening of the nucleotide binding domains is proposed to drive the translocation events. Despite clear structural similarities, evidence for considerable mechanistic diversity starts to accumulate within the importers subfamily. We present here a detailed study of the gating mechanism of a type II ABC importer, the BtuCD-F vitamin B(12) importer from Escherichia coli, elucidated by EPR spectroscopy. Distance changes at key positions in the translocation gates in the nucleotide-free, ATP- and ADP-bound conformations of the transporter were measured in detergent micelles and liposomes. The translocation gates of the BtuCD-F complex undergo conformational changes in line with a "two-state" alternating access model. We provide the first direct evidence that binding of ATP drives the gates to an inward-facing conformation, in contrast to type I importers specific for maltose, molybdate, or methionine. Following ATP hydrolysis, the translocation gates restore to an apo-like conformation. In the presence of ATP, an excess of vitamin B(12) promotes the reopening of the gates toward the periplasm and the dislodgment of BtuF from the transporter. The EPR data allow a productive translocation cycle of the vitamin B(12) transporter to be modeled.

SULT1A1, CYP2C19 and Disease-free Survival in Early Breast Cancer Patients Receiving Tamoxifen

Pharmacogenomics. Nov, 2011  |  Pubmed ID: 21961651

Tamoxifen biotransformation to endoxifen, a potent antiestrogen, is catalyzed by CYP2D6. In addition, CYP2C19 and SULT1A1 have also been implicated in the metabolism of tamoxifen. We sought to evaluate the importance of SULT1A1 copy number and CYP2C19*17 on disease-free survival (DFS) in postmenopausal women randomized to tamoxifen monotherapy in North Central Cancer Treatment Group 89-30-52 from January 1991 to April 1995.

Impact of a Kiosk Educational Module on HIV Screening Rates and Patient Knowledge

Journal of Telemedicine and Telecare. 2011  |  Pubmed ID: 21967998

We assessed the effect of a kiosk educational module on HIV screening rates and patient knowledge about HIV testing. The evaluation was performed in a walk-in clinic offering routine HIV screening. During alternating two-week periods, patients were referred either to view a kiosk-based, educational module prior to receiving usual care, or the kiosk module was turned off and no alterations to care processes were made. The primary outcome was HIV testing rate. The secondary outcome was knowledge about HIV rapid screening, as measured with a questionnaire. There were 71 patients in the kiosk periods and 79 patients in the usual-care periods. The overall HIV testing rate was 41%. The kiosk period was not associated with greater odds of HIV testing (OR 0.7; 95% CI: 0.4-1.4). In 44 patients who completed the knowledge survey, the kiosk group was strongly associated with increased knowledge (predicted increase in knowledge score: 1.3; 95% CI: 036-2.1). The brief kiosk educational module did not improve HIV screening rates, but it increased overall patient knowledge about HIV testing.

FIB-4 Index is Associated with Hepatocellular Carcinoma Risk in HIV-infected Patients

Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. Dec, 2011  |  Pubmed ID: 22028407

Chronic inflammation caused by hepatitis B virus infection, hepatitis C virus infection, and/or heavy alcohol use can lead to fibrosis, cirrhosis, and eventually hepatocellular carcinoma (HCC). FIB-4 is an index score calculated from platelet count, alanine transaminase, aspartate transaminase, and age that predicts fibrosis and cirrhosis. We hypothesized that high FIB-4 would be associated with development of HCC in HIV-infected persons, who are at high risk due to high prevalence of viral hepatitis and alcohol consumption, and possibly due to HIV infection itself.

Resolving the Evolutionary Relationships of Molluscs with Phylogenomic Tools

Nature. Dec, 2011  |  Pubmed ID: 22031330

Molluscs (snails, octopuses, clams and their relatives) have a great disparity of body plans and, among the animals, only arthropods surpass them in species number. This diversity has made Mollusca one of the best-studied groups of animals, yet their evolutionary relationships remain poorly resolved. Open questions have important implications for the origin of Mollusca and for morphological evolution within the group. These questions include whether the shell-less, vermiform aplacophoran molluscs diverged before the origin of the shelled molluscs (Conchifera) or lost their shells secondarily. Monoplacophorans were not included in molecular studies until recently, when it was proposed that they constitute a clade named Serialia together with Polyplacophora (chitons), reflecting the serial repetition of body organs in both groups. Attempts to understand the early evolution of molluscs become even more complex when considering the large diversity of Cambrian fossils. These can have multiple dorsal shell plates and sclerites or can be shell-less but with a typical molluscan radula and serially repeated gills. To better resolve the relationships among molluscs, we generated transcriptome data for 15 species that, in combination with existing data, represent for the first time all major molluscan groups. We analysed multiple data sets containing up to 216,402 sites and 1,185 gene regions using multiple models and methods. Our results support the clade Aculifera, containing the three molluscan groups with spicules but without true shells, and they support the monophyly of Conchifera. Monoplacophora is not the sister group to other Conchifera but to Cephalopoda. Strong support is found for a clade that comprises Scaphopoda (tusk shells), Gastropoda and Bivalvia, with most analyses placing Scaphopoda and Gastropoda as sister groups. This well-resolved tree will constitute a framework for further studies of mollusc evolution, development and anatomy.

Pain and Fatigue in Persons with Postpolio Syndrome: Independent Effects on Functioning

Archives of Physical Medicine and Rehabilitation. Nov, 2011  |  Pubmed ID: 22032213

To better understand the importance of pain and fatigue in relation to functioning, and to investigate the role that age plays in these relationships in individuals with postpolio syndrome (PPS).

Molecular Dynamics Simulations of the Effect of the G-protein and Diffusible Ligands on the β2-adrenergic Receptor

Journal of Molecular Biology. Dec, 2011  |  Pubmed ID: 22037586

G-protein-coupled receptors have extraordinary therapeutic potential as targets for a broad spectrum of diseases. Understanding their function at the molecular level is therefore essential. A variety of crystal structures have made the investigation of the inactive receptor state possible. Recently released X-ray structures of opsin and the β(2)-adrenergic receptor (β(2)AR) have provided insight into the active receptor state. In addition, we have contributed to the crystal structure of an irreversible agonist-β(2) adrenoceptor complex. These extensive studies and biophysical investigations have revealed that agonist binding leads to a low-affinity conformation of the active state that is suggested to facilitate G-protein binding. The high-affinity receptor state, which promotes signal transduction, is only formed in the presence of both agonist and G-protein. Despite numerous crystal structures, it is not yet clear how ligands tune receptor dynamics and G-protein binding. We have now used molecular dynamics simulations to elucidate the distinct impact of agonist and inverse agonist on receptor conformation and G-protein binding by investigating the influence of the ligands on the structure and dynamics of a complex composed of β(2)AR and the C-terminal end of the Gα(s) subunit (GαCT). The simulations clearly showed that the agonist isoprenaline and the inverse agonist carazolol influence the ligand-binding site and the interaction between β(2)AR and GαCT differently. Isoprenaline induced an inward motion of helix 5, whereas carazolol blocked the rearrangement of the extracellular part of the receptor. Moreover, in the presence of isoprenaline, β(2)AR and GαCT form a stable interaction that is destabilized by carazolol.

Synthesis of Well-ordered COF Monolayers: Surface Growth of Nanocrystalline Precursors Versus Direct On-surface Polycondensation

ACS Nano. Dec, 2011  |  Pubmed ID: 22040355

Two different straightforward synthetic approaches are presented to fabricate long-range-ordered monolayers of a covalent organic framework (COF) on an inert, catalytically inactive graphite surface. Boronic acid condensation (dehydration) is employed as the polymerization reaction. In the first approach, the monomer is prepolymerized by a mere thermal treatment into nanocrystalline precursor COFs. The precursors are then deposited by drop-casting onto a graphite substrate and characterized by scanning tunneling microscopy (STM). While in the precursors monomers are already covalently interlinked into the final COF structure, the resulting domain size is still rather small. We show that a thermal treatment under reversible reaction conditions facilitates on-surface ripening associated with a striking increase of the domain size. Although this first approach allows studying different stages of the polymerization, the direct polymerization, that is, without the necessity of preceding reaction steps, is desirable. We demonstrate that even for a comparatively small diboronic acid monomer a direct thermally activated polymerization into extended COF monolayers is achievable.

CYP2D6 and Tamoxifen: Awaiting the Denouement

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. Dec, 2011  |  Pubmed ID: 22042960

Effectiveness of a Quality-improvement Program in Improving Management of Primary Care Practices

CMAJ : Canadian Medical Association Journal = Journal De L'Association Medicale Canadienne. Dec, 2011  |  Pubmed ID: 22043000

The European Practice Assessment program provides feedback and outreach visits to primary care practices to facilitate quality improvement in five domains (infrastructure, people, information, finance, and quality and safety). We examined the effectiveness of this program in improving management in primary care practices in Germany, with a focus on the domain of quality and safety.

RNA-Seq Reveals an Integrated Immune Response in Nucleated Erythrocytes

PloS One. 2011  |  Pubmed ID: 22046430

Throughout the primary literature and within textbooks, the erythrocyte has been tacitly accepted to have maintained a unique physiological role; namely gas transport and exchange. In non-mammalian vertebrates, nucleated erythrocytes are present in circulation throughout the life cycle and a fragmented series of observations in mammals support a potential role in non-respiratory biological processes. We hypothesised that nucleated erythrocytes could actively participate via ligand-induced transcriptional re-programming in the immune response.

Questionnaire of Chronic Illness Care in Primary Care-psychometric Properties and Test-retest Reliability

BMC Health Services Research. 2011  |  Pubmed ID: 22047211

The Chronic Care Model (CCM) is an evidence-based approach to improving the structure of care for chronically ill patients with multimorbidity. The Assessment of Chronic Illness Care (ACIC), an instrument commonly used in international research, includes all aspects of the CCM, but cannot be easily extended to the German context. A new instrument called the "Questionnaire of Chronic Illness Care in Primary Care" (QCPC) was developed for use in Germany for this reason. Here, we present the results of the psychometric properties and test-retest reliability of QCPC.

The Movement Disorder Society Evidence-Based Medicine Review Update: Treatments for the Motor Symptoms of Parkinson's Disease

Movement Disorders : Official Journal of the Movement Disorder Society. Oct, 2011  |  Pubmed ID: 22021173

The objective was to update previous evidence-based medicine reviews of treatments for motor symptoms of Parkinson's disease published between 2002 and 2005. Level I (randomized, controlled trial) reports of pharmacological, surgical, and nonpharmacological interventions for the motor symptoms of Parkinson's disease between January 2004 (2001 for nonpharmacological) and December 2010 were reviewed. Criteria for inclusion, clinical indications, ranking, efficacy conclusions, safety, and implications for clinical practice followed the original program outline and adhered to evidence-based medicine methodology. Sixty-eight new studies qualified for review. Piribedil, pramipexole, pramipexole extended release, ropinirole, rotigotine, cabergoline, and pergolide were all efficacious as symptomatic monotherapy; ropinirole prolonged release was likely efficacious. All were efficacious as a symptomatic adjunct except pramipexole extended release, for which there is insufficient evidence. For prevention/delay of motor fluctuations, pramipexole and cabergoline were efficacious, and for prevention/delay of dyskinesia, pramipexole, ropinirole, ropinirole prolonged release, and cabergoline were all efficacious, whereas pergolide was likely efficacious. Duodenal infusion of levodopa was likely efficacious in the treatment of motor complications, but the practice implication is investigational. Entacapone was nonefficacious as a symptomatic adjunct to levodopa in nonfluctuating patients and nonefficacious in the prevention/delay of motor complications. Rasagiline conclusions were revised to efficacious as a symptomatic adjunct, and as treatment for motor fluctuations. Clozapine was efficacious in dyskinesia, but because of safety issues, the practice implication is possibly useful. Bilateral subthalamic nucleus deep brain stimulation, bilateral globus pallidus stimulation, and unilateral pallidotomy were updated to efficacious for motor complications. Physical therapy was revised to likely efficacious as symptomatic adjunct therapy. This evidence-based medicine review updates the field and highlights gaps for research.

The Movement Disorder Society Evidence-Based Medicine Review Update: Treatments for the Non-motor Symptoms of Parkinson's Disease

Movement Disorders : Official Journal of the Movement Disorder Society. Oct, 2011  |  Pubmed ID: 22021174

The Movement Disorder Society (MDS) Task Force on Evidence-Based Medicine (EBM) Review of Treatments for Parkinson's Disease (PD) was first published in 2002 and was updated in 2005 to cover clinical trial data up to January 2004 with the focus on motor symptoms of PD. In this revised version the MDS task force decided it was necessary to extend the review to non-motor symptoms. The objective of this work was to update previous EBM reviews on treatments for PD with a focus on non-motor symptoms. Level-I (randomized controlled trial, RCT) reports of pharmacological and nonpharmacological interventions for the non-motor symptoms of PD, published as full articles in English between January 2002 and December 2010 were reviewed. Criteria for inclusion and ranking followed the original program outline and adhered to EBM methodology. For efficacy conclusions, treatments were designated: efficacious, likely efficacious, unlikely efficacious, non-efficacious, or insufficient evidence. Safety data were catalogued and reviewed. Based on the combined efficacy and safety assessment, Implications for clinical practice were determined using the following designations: clinically useful, possibly useful, investigational, unlikely useful, and not useful. Fifty-four new studies qualified for efficacy review while several other studies covered safety issues. Updated and new efficacy conclusions were made for all indications. The treatments that are efficacious for the management of the different non-motor symptoms are as follows: pramipexole for the treatment of depressive symptoms, clozapine for the treatment of psychosis, rivastigmine for the treatment of dementia, and botulinum toxin A (BTX-A) and BTX-B as well as glycopyrrolate for the treatment of sialorrhea. The practical implications for these treatments, except for glycopyrrolate, are that they are clinically useful. Since there is insufficient evidence of glycopyrrolate for the treatment of sialorrhea exceeding 1 week, the practice implication is that it is possibly useful. The treatments that are likely efficacious for the management of the different non-motor symptoms are as follows: the tricyclic antidepressants nortriptyline and desipramine for the treatment of depression or depressive symptoms and macrogol for the treatment of constipation. The practice implications for these treatments are possibly useful. For most of the other interventions there is insufficient evidence to make adequate conclusions on their efficacy. This includes the tricyclic antidepressant amitriptyline, all selective serotonin reuptake inhibitors (SSRIs) reviewed (paroxetine, citalopram, sertraline, and fluoxetine), the newer antidepressants atomoxetine and nefazodone, pergolide, Ω-3 fatty acids as well as repetitive transcranial magnetic stimulation (rTMS) for the treatment of depression or depressive symptoms; methylphenidate and modafinil for the treatment of fatigue; amantadine for the treatment of pathological gambling; donepezil, galantamine, and memantine for the treatment of dementia; quetiapine for the treatment of psychosis; fludrocortisone and domperidone for the treatment of orthostatic hypotension; sildenafil for the treatment of erectile dysfunction, ipratropium bromide spray for the treatment of sialorrhea; levodopa/carbidopa controlled release (CR), pergolide, eszopiclone, melatonin 3 to 5 mg and melatonin 50 mg for the treatment of insomnia and modafinil for the treatment of excessive daytime sleepiness. Due to safety issues the practice implication is that pergolide and nefazodone are not useful for the above-mentioned indications. Due to safety issues, olanzapine remains not useful for the treatment of psychosis. As none of the studies exceeded a duration of 6 months, the recommendations given are for the short-term management of the different non-motor symptoms. There were no RCTs that met inclusion criteria for the treatment of anxiety disorders, apathy, medication-related impulse control disorders and related behaviors other than pathological gambling, rapid eye movement (REM) sleep behavior disorder (RBD), sweating, or urinary dysfunction. Therefore, there is insufficient evidence for the treatment of these indications. This EBM review of interventions for the non-motor symptoms of PD updates the field, but, because several RCTs are ongoing, a continual updating process is needed. Several interventions and indications still lack good quality evidence, and these gaps offer an opportunity for ongoing research. © 2011 Movement Disorder Society.

Comparative Evaluation of Pharmaceutical Products Obtained in Mexico: Augmenting Existing Scientific Data

Drug Development and Industrial Pharmacy. Nov, 2011  |  Pubmed ID: 22091930

Context: The accessibility of pharmacies in neighboring countries has facilitated the trend of acquiring medications outside of local borders. However, scientific data assessing the drug content and quality of these medications has not increased in a corresponding fashion. Objective: This study seeks to augment existing scientific data. Materials and methods: Seventeen products that were obtained from pharmacies in Mexico were evaluated for active ingredient content. The active pharmaceutical ingredients (API) assessed included amoxicillin, ampicillin, ciprofloxacin, levothyroxine, sildenafil citrate, sulfamethoxazole, trimethoprim, and warfarin. API content was analysed with high performance liquid chromatography assays and the resultant data interpreted by applying United States Pharmacopeia (USP) acceptability limits. Results: All of the samples analyzed for the two ciprofloxacin products and the two ampicillin products were found to be within the USP limits. Of the four different sulfamethoxazole/trimethoprim products tested, all were within USP limits for sulfamethoxazole, but contained 2-3 individual units which were outside of USP limits for trimethoprim. Several of the remaining products (amoxicillin, levothyroxine, sildenafil citrate, and warfarin) had individual units that fell outside of the USP limits, although only one of the levothyroxine products (1 out of 20 tablets tested) and both sildenafil citrate products (all of the units tested) contained units outside of ±25% label claim.

Clinical, Histologic and Histomorphometric Evaluation of Socket Preservation Using a Synthetic Nanocrystalline Hydroxyapatite in Comparison with a Bovine Xenograft: a Randomized Clinical Trial

Clinical Oral Implants Research. Aug, 2011  |  Pubmed ID: 22092485

OBJECTIVES: The aim of this study was to compare a nanocrystalline hydroxyapatite (NCHA), NanoBone(®) and a deproteinized bovine bone mineral (DBBM), Bio-Oss(®) with a collagen membrane on the horizontal ridge width alterations following tooth extraction, in addition to histologic aspects of the grafted extraction sockets. MATERIAL AND METHODS: In this randomized clinical trial, 28 symmetrical, non-molar, extraction sockets using a split-mouth design in 12 patients (eight women and four men; aged 21-60; mean 44.6 ± 11.4 years), were randomly selected in the first group to be grafted with DBBM granules covered with a collagen membrane and in the other group grafted with NCHA covered with a collagen membrane. Following extraction horizontal ridge width was measured using caliper and was blindly compared to the dimensions measured prior to implant placement, at the 6- to 8-month follow-up. Subsequently, a 2 × 6 mm trephine core was obtained with aid of acrylic stent and routine histologic preparation was performed on the specimens. RESULTS: The width of the DBBM group decreased from 7.75 ± 1.55 to 6.68 ± 1.85 mm (P < 0.05), whereas the width of the NCHA group decreased from 7.36 ± 1.94 to 6.43 ± 2.08 mm (P < 0.05). The mean between-group difference did not reach statistical significance (P = 0.62). Furthermore, histologic and histomorphometric analyses revealed 28.63 ± 12.53% vital bone in NCHA group vs. 27.35 ± 12.39% in DBBM group, and no statistically significant difference between the groups (P = 0.68). CONCLUSION: Socket preservation using either NCHA or DBBM in combination with collagen membrane, results in similar, limited horizontal ridge width alterations following tooth extraction.

Evaluation of Job Satisfaction of Practice Staff and General Practitioners: an Exploratory Study

BMC Family Practice. 2011  |  Pubmed ID: 22151354

Primary care teams' job satisfaction is an important issue in quality of care. The purpose of our study was to evaluate the job satisfaction of general practitioners (GPs) and non-physician staff and to explore the elements that may impact on overall job satisfaction for GPs and non-physician staff separately.

Launching Nurse-initiated HIV Rapid Testing in Veterans Affairs Primary Care: a Comprehensive Overview of a Self-sustaining Implementation

International Journal of STD & AIDS. Dec, 2011  |  Pubmed ID: 22174056

Our objectives were to use foundational pilot findings to guide the implementation of an HIV rapid testing (RT) intervention at one Veterans Affairs outpatient clinic and to evaluate the success and sustainability of this intervention over the course of one year. Policy modifications were drafted and adopted to enable nurses to order, administer, interpret and document HIV RTs. Staff enrolled in a two-part training sessions designed to teach pre- and post-test counselling techniques and the mechanics of administering, interpreting and coding test results in the patients' medical records. They were subsequently evaluated on their efforts at: (1) increasing HIV RT, (2) sustaining this effort one year post-launch. Enabling nurses to carry out HIV RT resulted in a significant increase in not only HIV RT, but also HIV testing rates overall at this facility, measured over the first year of this implementation. Our findings indicate that targeted strategies, aimed at increasing HIV RT rates, worked to increase testing rates overall, and also, that our initial testing strategies were independently sustainable, which is in contrast to findings in the literature on implementation science.

Characteristics and Job Satisfaction of General Practitioners Using Complementary and Alternative Medicine in Germany--is There a Pattern?

BMC Complementary and Alternative Medicine. 2011  |  Pubmed ID: 22182710

The use of Complementary and Alternative medicine (CAM) has increased over the past years. In Germany, many general practitioners (GPs) use CAM in their daily practice. However, little is known about possible differences of GPs using CAM compared to GPs not using CAM. The aim of the study was to explore differences in personal and practice characteristics, work load and job satisfaction of GPs depending on their use of and attitude towards CAM. Furthermore, predictors for CAM use should be explored.

Phase I-II Study of Vorinostat Plus Paclitaxel and Bevacizumab in Metastatic Breast Cancer: Evidence for Vorinostat-induced Tubulin Acetylation and Hsp90 Inhibition in Vivo

Breast Cancer Research and Treatment. Dec, 2011  |  Pubmed ID: 22200869

In preclinical models, the histone deacetylase inhibitor vorinostat sensitizes breast cancer cells to tubulin-polymerizing agents and to anti-vascular endothelial growth factor-directed therapies. We sought to determine the safety and efficacy of vorinostat plus paclitaxel and bevacizumab as first-line therapy in metastatic breast cancer (MBC), and the biological effects of vorinostat in vivo. For this purpose of this study, 54 patients with measurable disease and no prior chemotherapy for MBC received vorinostat (200 or 300 mg PO BID) on days 1-3, 8-10, and 15-17, plus paclitaxel (90 mg/m(2)) on days 2, 9, 16, and bevacizumab (10 mg/kg) on days 2 and 16 every 28 days. The primary objective of the phase I study was to determine the recommended phase II dose (RPTD) of vorinostat, and for the phase II to detect an improvement of response rate from 40 to 60% (alpha = 0.10, beta = 0.10). No dose limiting toxicities were observed, and the RPTD of vorinostat was 300 mg BID. For the primary efficacy analysis in 44 patients at the RPTD, we observed 24 objective responses (55%, 95% confidence intervals (C.I) 39%, 70%). The adverse event profile was consistent with paclitaxel-bevacizumab, with the exception of increased diarrhea with the addition of vorinostat. Analysis of serial tumor biopsies in seven patients showed increased acetylation of Hsp90 and α-tubulin following vorinostat. Vorinostat induces histone and alpha tubulin acetylation and functional inhibition of Hsp90 in breast cancer in vivo and can be safely combined with paclitaxel and bevacizumab.

Rural Residence and Adoption of a Novel HIV Therapy in a National, Equal-Access Healthcare System

AIDS and Behavior. Dec, 2011  |  Pubmed ID: 22205324

Rural persons with HIV face barriers to care that may influence adoption of advances in therapy. We performed a retrospective cohort study to determine rural-urban variation in adoption of raltegravir-the first HIV integrase inhibitor-in national Veterans Afffairs (VA) healthcare. There were 1,222 veterans with clinical indication for raltegravir therapy at time of its FDA approval in October 2007, of whom 223 (19.1%) resided in rural areas. Urban persons were more likely than rural to initiate raltegravir within 180 days (17.3% vs. 11.2%, P = 0.02) and 360 days (27.5% vs. 19.7%, P = 0.02), but this gap narrowed slightly at 720 days (36.3% vs. 31.8%, P = 0.19). In multivariable analysis adjusting for patient characteristics, urban residence predicted raltegravir adoption within 180 days (odds ratio 1.72, 95% CI 1.09-2.70) and 360 days (OR 1.63, 95% CI 1.13-2.34), but not 720 days (OR 1.26, 95% CI 0.84-1.87). Efforts are needed to reduce geographic variation in adoption of advances in HIV therapy.

Evaluation of VIDAS Salmonella (SLM) Easy Salmonella Method for the Detection of Salmonella in a Variety of Foods: Collaborative Study

Journal of AOAC International. Nov-Dec, 2011  |  Pubmed ID: 22320090

The VIDAS Salmonella (SLM) Easy Salmonella method is a specific enzyme-linked fluorescent immunoassay performed in the automated VIDAS instrument. The VIDAS Easy Salmonella method is a simple 2-step enrichment procedure, using pre-enrichment followed by selective enrichment in a newly formulated broth, SX2 broth. This new method was compared in a multilaboratory collaborative study to the U.S. Food and Drug Administration's Bacteriological Analytical Manual, Chapter 5 method for five food matrixes (liquid egg, vanilla ice cream, spinach, raw shrimp, and peanut butter) and the U.S. Department of Agriculture's Microbiology Laboratory Guidebook 4.04 method for deli turkey. Each food type was artificially contaminated with Salmonella at three inoculation levels. A total of 15 laboratories representing government, academia, and industry, throughout the United States, participated. In this study, 1583 samples were analyzed, of which 792 were paired replicates and 791 were unpaired replicates. Of the 792 paired replicates, 285 were positive by both the VIDAS and reference methods. Of the 791 unpaired replicates, 341 were positive by the VIDAS method and 325 were positive by the cultural reference method. A Chi-square analysis of each of the six food types was performed at the three inoculation levels tested. For all foods evaluated, the VIDAS Easy SLM method demonstrated results comparable to those of the reference methods for the detection of Salmonella.

Successful Weaning from Extracorporal Circulation Using a Pumpless Extracorporal Lung Assist Device in a Patient with Intraoperative Hypercapnic Lung Failure During Aortic Valve Replacement

The Thoracic and Cardiovascular Surgeon. Mar, 2011  |  Pubmed ID: 21442582

We present a case of a 59-year-old female suffering from massive pulmonary edema with consecutive hypercapnic lung failure immediately following elective aortic valve replacement. Due to severe restrictive ventilation disorder, mechanical ventilation was inadequate. A pumpless lung assist (PECLA, iLA, Novalung®, Talheim, Germany) - a device for extracorporeal carbon dioxide elimination - was used for successful weaning from extracorporeal circulation (ECC). Within 24 hours respiratory function had normalized and the patient could be extubated. The further clinical course and follow-up at 3 months remained uneventful. This report describes the first intraoperative use of the PECLA device in a cardiac surgery patient to promote weaning from ECC.

Disruption of the Salmon Reproductive Endocrine Axis Through Prolonged Nutritional Stress: Changes in Circulating Hormone Levels and Transcripts for Ovarian Genes Involved in Steroidogenesis and Apoptosis

General and Comparative Endocrinology. Jul, 2011  |  Pubmed ID: 21447335

Mechanisms regulating the normal progression of ovarian follicular growth versus onset of atresia in fishes are poorly understood. To gain a better understanding of these processes, we exposed immature female coho salmon (Oncorhynchus kisutch) to prolonged fasting to induce follicular atresia and monitored body growth, development of the ovarian follicles, changes in reproductive hormones, and transcripts for ovarian genes. Prolonged fasting reduced body and ovary weight and increased the appearance of atretic follicles relative to normally fed controls. Endocrine analyses showed that fasting reduced plasma insulin-like growth factor 1 (IGF1), estradiol-17β (E2), and pituitary, but not plasma, levels of follicle-stimulating hormone (FSH). Transcripts for ovarian fsh receptor (fshr) and steroidogenesis-related genes, such as steroidogenic acute regulatory protein (star), 3β-hydroxysteroid dehydrogenase (hsd3b), and P450 aromatase (cyp19a1a) were significantly lower in fasted fish. Ovarian expression of apoptosis-related genes, such as Fas-associated death domain (fadd), caspase 8 (casp8), caspase 3 (casp3), and caspase 9 (casp9) were significantly elevated in fasted fish compared to fed fish, indicating that apoptosis is involved in the process of atresia in this species. Interestingly, some genes such as fadd, casp8, casp3, and hsd3b, were differentially expressed prior to increases in the number of atretic follicles and reductions in hormone levels induced by fasting, and may therefore have potential as early indicators of atresia. Together these results suggest that prolonged nutritional stress may disrupt the reproductive system and induce follicular atresia in part via reductions in ovarian IGF and FSH signaling, and downstream effects on steroidogenesis-related genes and E2 production.

Aberrant Course of the Intracranial Facial Nerve in Cases of Atresia of the Internal Auditory Canal (IAC)

Neuroradiology. Sep, 2011  |  Pubmed ID: 21448638

The aim of this study is to describe the morphology of the rare malformation that is atresia of the internal auditory canal (IAC) and determine the course of the facial nerve in cases of normal facial nerve function.

Adaptation of an ICAM-1-tropic Enterovirus to the Mouse Respiratory Tract

Journal of Virology. Jun, 2011  |  Pubmed ID: 21450825

Respiratory tract (RT) infections by members of the enterovirus (EV) genus of the Picornaviridae family are the most frequent cause for the common cold and a major factor in the exacerbation of chronic pulmonary diseases. The lack of a practical small-animal model for these infections has obstructed insight into pathogenic mechanisms of the common cold and their role in chronic RT illness and has hampered preclinical evaluation of antiviral strategies. Despite significant efforts, it has been difficult to devise rodent models that exhibit viral replication in the RT. This is due mainly to well-known intracellular host restrictions of EVs with RT tropism in rodent cells. We report the evolution of variants of the common-cold-causing coxsackievirus A21, an EV with tropism for the human intercellular adhesion molecule 1 (hICAM-1), through serial passage in the lungs of mice transgenic for the hICAM-1 gene. This process was accompanied by multiple changes in the viral genome, suggesting exquisite adaptation of hICAM-1-tropic enteroviruses to the specific growth conditions within the RT. In vivo mouse RT-adapted, variant coxsackievirus A21 exhibited replication competence in the lungs of hICAM-1 transgenic mice, providing a basis for unraveling EV-host interactions in the mouse RT.

PAMPs, PRRs and the Genomics of Gram Negative Bacterial Recognition in Fish

Developmental and Comparative Immunology. Dec, 2011  |  Pubmed ID: 21453721

Understanding the mechanisms that underpin pathogen recognition and subsequent orchestration of the immune response in fish is an area of significant importance for both basic research and management of health in aquaculture. In recent years much attention has been given to the identification of pattern recognition receptors (PRRs) in fish, however, characterisation of interactions with specific pathogen-associated molecular patterns (PAMPs) is still incomplete. Microarray studies have significantly contributed to functional studies and early descriptions of PAMP-PRR driven activation of specific response cassettes in the genome have been obtained although much is left to be done. In this review we will address gram negative (G-negative) bacterial recognition in fish addressing contributing factors such as structure-function relationships between G-negative PAMPs, current knowledge of fish PRRs and the input achieved by microarray-based studies ranging from in vivo infection studies to directed in vitro PAMP-cell studies. Finally we revisit the endotoxic recognition paradigm in fish and suggest a series of future perspectives that could contribute toward the further elucidation of G-negative bacterial recognition across the highly diverse group of vertebrates that encompass the fishes.

Application of Laser Postionization Secondary Neutral Mass Spectrometry/time-of-flight Secondary Ion Mass Spectrometry in Nanotoxicology: Visualization of Nanosilver in Human Macrophages and Cellular Responses

ACS Nano. Apr, 2011  |  Pubmed ID: 21456612

Silver nanoparticles (SNP) are the subject of worldwide commercialization because of their antimicrobial effects. Yet only little data on their mode of action exist. Further, only few techniques allow for visualization and quantification of unlabeled nanoparticles inside cells. To study SNP of different sizes and coatings within human macrophages, we introduce a novel laser postionization secondary neutral mass spectrometry (Laser-SNMS) approach and prove this method superior to the widely applied confocal Raman and transmission electron microscopy. With time-of-flight secondary ion mass spectrometry (TOF-SIMS) we further demonstrate characteristic fingerprints in the lipid pattern of the cellular membrane indicative of oxidative stress and membrane fluidity changes. Increases of protein carbonyl and heme oxygenase-1 levels in treated cells confirm the presence of oxidative stress biochemically. Intriguingly, affected phagocytosis reveals as highly sensitive end point of SNP-mediated adversity in macrophages. The cellular responses monitored are hierarchically linked, but follow individual kinetics and are partially reversible.

ATM-dependent IGF-1 Induction Regulates Secretory Clusterin Expression After DNA Damage and in Genetic Instability

Oncogene. Sep, 2011  |  Pubmed ID: 21460853

Secretory clusterin (sCLU) is a stress-induced, pro-survival glycoprotein elevated in early-stage cancers, in particular in APC/Min-defective colon cancers. sCLU is upregulated after exposure to various cytotoxic agents, including ionizing radiation (IR), leading to a survival advantage. We found that stimulation of insulin-like growth factor-1 (IGF-1) and IGF-1R protein kinase signaling was required for sCLU induction after IR exposure. Here, we show that activation of Ataxia telangiectasia-mutated kinase (ATM) by endogenous or exogenous forms of DNA damage was required to relieve basal repression of IGF-1 transcription by the p53/NF-YA complex, leading to sCLU expression. Although p53 levels were stabilized and elevated after DNA damage, dissociation of NF-YA, and thereby p53, from the IGF-1 promoter resulted in IGF-1 induction, indicating that NF-YA was rate limiting. Cells with elevated endogenous DNA damage (deficient in H2AX, MDC1, NBS1, mTR or hMLH1) or cells exposed to DNA-damaging agents had elevated IGF-1 expression, resulting in activation of IGF-1R signaling and sCLU induction. In contrast, ATM-deficient cells were unable to induce sCLU after DNA damage. Our results integrate DNA damage resulting from genetic instability, IR, or chemotherapeutic agents, to ATM activation and abrogation of p53/NF-YA-mediated IGF-1 transcriptional repression, that induces IGF-1-sCLU expression. Elucidation of this pathway should uncover new mechanisms for cancer progression and reveal new targets for drug development to overcome resistance to therapy.

Immunological Stimuli Change Expression of Genes and Neutrophil Function in Fathead Minnow Pimephales Promelas Rafinesque

Journal of Fish Biology. Apr, 2011  |  Pubmed ID: 21463307

Fathead minnows Pimephales promelas were exposed to lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid [poly(I:C)] to observe immunological responses during simulated bacterial and viral challenge at the level of gene expression and granulocyte function. Complementary DNA libraries were created from LPS- and poly(I:C)-treated fish and c. 5000 expressed sequence tags (ESTs) were sequenced. The ESTs were subjected to BLASTx analysis and 1500 genes were annotated, grouped by function and 20 immune genes were selected for expression studies by real-time PCR. Lipopolysaccharide treatment significantly downregulated expression of interferon regulatory factor 2 binding protein 1 (nine-fold), Chemokine (C-X-C motif) ligand 12a (three-fold) and TNF-related apoptosis-inducing ligand, TRAIL (two-fold). In poly(I:C)-treated fish, a significant upregulation was observed for IFN-inducible and antiviral proteins belonging to the family of Mx proteins (73-fold) and chemokine CCL-C5a (28-fold). Blood neutrophil count was significantly increased in poly(I:C)-treated fish at 24 and 48 h post-injection. Neutrophil extracellular trap release and respiratory burst of kidney granulocytes were suppressed in poly(I:C)-treated fish, while degranulation of primary granules was not affected significantly by the treatment. The changes in gene expression and neutrophil function in P. promelas exposed to LPS and poly(I:C) support the use of this species as an alternative model for studies of pathogen effects on the innate immune system of fishes.

[Further Education in Anesthesiology. Implementation at the University Hospital Hamburg-Eppendorf]

Der Anaesthesist. Apr, 2011  |  Pubmed ID: 21479708

Due to the lack of physicians and the changing demands of junior staff more attractive curricula are needed in anesthesiology in Germany. In the German Society of Anesthesiology and Intensive Care Medicine as well as the Association of German Anesthesiologists discussions on the optimization of training have a long tradition. The following article gives a description of the concept and the practical approach to the training curricular at the University Hospital Hamburg-Eppendorf and is designed to stimulate discussion on possible concepts for training in anesthesiology.

Interactive Internet-based Clinical Education: an Efficient and Cost-savings Approach to Point-of-care Test Training

Telemedicine Journal and E-health : the Official Journal of the American Telemedicine Association. Jun, 2011  |  Pubmed ID: 21492031

We successfully created and implemented an effective HIV rapid testing training and certification curriculum using traditional in-person training at multiple sites within the U.S. Department of Veterans Affairs (VA) Healthcare System.

Racial Differences May Influence the Role of Cholecystokinin Polymorphisms in Parkinson's Disease Hallucinations

Movement Disorders : Official Journal of the Movement Disorder Society. Aug, 2011  |  Pubmed ID: 21506165

Risk of Heart Failure with Human Immunodeficiency Virus in the Absence of Prior Diagnosis of Coronary Heart Disease

Archives of Internal Medicine. Apr, 2011  |  Pubmed ID: 21518940

Whether human immunodeficiency virus (HIV) infection is a risk factor for heart failure (HF) is not clear. The presence of coronary heart disease and alcohol consumption in this population may confound this association.

Subthalamic Neuronal Firing in Obsessive-compulsive Disorder and Parkinson Disease

Annals of Neurology. May, 2011  |  Pubmed ID: 21520240

Although electrophysiologic dysfunction of the subthalamic nucleus is putative, deep brain stimulation of this structure has recently been reported to improve obsessions and compulsions. In Parkinson disease, sensorimotor subthalamic neurons display high-frequency burst firing, which is considered as an electrophysiologic signature of motor loop dysfunction. We addressed whether such neuronal dysfunction of the subthalamic nucleus also exists in the nonmotor loops involved in patients with obsessive-compulsive disorder.

Synthesis of Fluorescently Labelled Rhamnosides: Probes for the Evaluation of Rhamnogalacturonan II Biosynthetic Enzymes

Carbohydrate Research. Sep, 2011  |  Pubmed ID: 21530947

Three fluorescently labelled saccharides 10-12, representing structures found in pectic glycan rhamnogalacturonan II (RG-II), were synthesised by chemical glycosylation of O-6 of diacetone-d-galactose followed by deprotection and reductive amination with amino-substituted fluorophore APTS. This convenient method installs a common aminogalactitol-based tether in order to preserve the integrity of the reducing end of specific carbohydrates of interest. APTS-labelled glycans prepared in this manner were purified by carbohydrate gel electrophoresis and subjected to capillary electrophoresis analysis, as a basis for the subsequent development of high sensitivity assays for RG-II-active enzymes.

Priorities in Parkinson's Disease Research

Nature Reviews. Drug Discovery. May, 2011  |  Pubmed ID: 21532567

The loss of dopaminergic neurons in the substantia nigra pars compacta leads to the characteristic motor symptoms of Parkinson's disease: bradykinesia, rigidity and resting tremors. Although these symptoms can be improved using currently available dopamine replacement strategies, there is still a need to improve current strategies of treating these symptoms, together with a need to alleviate non-motor symptoms of the disease. Moreover, treatments that provide neuroprotection and/or disease-modifying effects remain an urgent unmet clinical need. This Review describes the most promising biological targets and therapeutic agents that are currently being assessed to address these treatment goals. Progress will rely on understanding genetic mutations or susceptibility factors that lead to Parkinson's disease, better translation between preclinical animal models and clinical research, and improving the design of future clinical trials.

The Movement Disorders Task Force Review of Dysautonomia Rating Scales in Parkinson's Disease with Regard to Symptoms of Orthostatic Hypotension

Movement Disorders : Official Journal of the Movement Disorder Society. Sep, 2011  |  Pubmed ID: 21547951

Orthostatic hypotension is defined as a blood pressure fall of > 20 mm Hg systolic and/or 10 mm Hg diastolic within 3 minutes of an upright position. The Movement Disorders Society commissioned a task force to assess existing clinical rating scales addressing symptoms of orthostatic hypotension in Parkinson's disease. Seven neurologists and a clinimetrician assessed each scale's previous use and critiqued its clinimetric properties. A scale was "recommended" if it had been applied to populations of patients with Parkinson's disease, with data on its use in studies beyond the group that developed the scale, and was found to be clinimetrically valid. A scale was considered "suggested" if it had been applied to Parkinson's disease, but only 1 of the other criteria was applied. A scale was "listed" if it met only 1 criterion. Symptoms of orthostatic hypotension are generally assessed in scales on wider autonomic or nonmotor symptoms. Some scales designed to detect orthostatic hypotension-related symptoms provide information on their severity: the AUTonomic SCale for Outcomes in PArkinson's Disease and the COMPosite Autonomic Symptom Scale met criteria for recommended with some limitations; the Novel Non-Motor Symptoms Scale and the Orthostatic Grading Scale were classified as suggested. The Self-completed Non-Motor Symptoms Questionnaire for Parkinson's Disease was classified as suggested as a tool for screening orthostatic symptoms. However, these and the listed scales need further validation and application before they can be recommended for clinical use in patients with Parkinson's disease.

Becoming a General Practitioner--which Factors Have Most Impact on Career Choice of Medical Students?

BMC Family Practice. 2011  |  Pubmed ID: 21549017

In Germany, there is a shortage of young physicians in several specialties, the situation of general practitioners (GP) being especially precarious. The factors influencing the career choice of German medical students are poorly understood. This study aims to identify factors influencing medical students' specialty choice laying a special focus on general practice.

Termination of Washing Compulsions: a Problem of Internal Reference Criteria or 'not Just Right' Experience?

Journal of Anxiety Disorders. Aug, 2011  |  Pubmed ID: 21549560

Recent research suggests that obsessive-compulsive washers are more likely than individuals without washing compulsions to use conscious, internal reference criteria when deciding when to terminate compulsions (Wahl, Salkovskis, & Cotter, 2008). An alternative view is that they possess tendencies towards non-cognitive, automatic 'not just right' experiences (NJREs) that influence compulsion duration. The current study sought to investigate the latter explanation using valid behavioral tasks. Non-clinical participants (N=133) completed self-report measures, immersed their hands in a dirt mixture, and afterwards were allowed to wash their hands. Additionally, a subset of participants completed an in vivo assessment of NJRE using a pile of clutter. Total number and intensity of NJREs were predictive of hand-washing duration. Additionally, affective response to the clutter was uniquely predictive of hand-washing duration when controlling for pre-wash anxiety. These results suggest that internal reference criteria as well as NJREs may influence compulsive washing, though the former may be a consequence of the latter.

Supercritical Carbon Dioxide Pretreatment of Corn Stover and Switchgrass for Lignocellulosic Ethanol Production

Bioresource Technology. Jul, 2011  |  Pubmed ID: 21555219

Supercritical CO(2) (SC-CO(2)), a green solvent suitable for a mobile lignocellulosic biomass processor, was used to pretreat corn stover and switchgrass at various temperatures and pressures. The CO(2) pressure was released as quickly as possible by opening a quick release valve during the pretreatment. The biomass was hydrolyzed after pretreatment using cellulase combined with β-glucosidase. The hydrolysate was analyzed for the amount of glucose released. Glucose yields from corn stover samples pretreated with SC-CO(2) were higher than the untreated sample's 12% glucose yield (12 g/100g dry biomass) and the highest glucose yield of 30% was achieved with SC-CO(2) pretreatment at 3500 psi and 150°C for 60 min. The pretreatment method showed very limited improvement (14% vs. 12%) in glucose yield for switchgrass. X-ray diffraction results indicated no change in crystallinity of the SC-CO(2) treated corn stover when compared to the untreated, while SEM images showed an increase in surface area.

Regulation of Serum 1,25(OH)2 Vitamin D3 Levels by Fibroblast Growth Factor 23 is Mediated by FGF Receptors 3 and 4

American Journal of Physiology. Renal Physiology. Aug, 2011  |  Pubmed ID: 21561999

Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone implicated in the pathogenesis of several hypophosphatemic disorders. FGF23 causes hypophosphatemia by decreasing the expression of sodium phosphate cotransporters (NaPi-2a and NaPi-2c) and decreasing serum 1,25(OH)(2)Vitamin D(3) levels. We previously showed that FGFR1 is the predominant receptor for the hypophosphatemic actions of FGF23 by decreasing renal NaPi-2a and 2c expression while the receptors regulating 1,25(OH)(2)Vitamin D(3) levels remained elusive. To determine the FGFRs regulating 1,25(OH)(2)Vitamin D(3) levels, we studied FGFR3(-/-)FGFR4(-/-) mice as these mice have shortened life span and are growth retarded similar to FGF23(-/-) and Klotho(-/-) mice. Baseline serum 1,25(OH)(2)Vitamin D(3) levels were elevated in the FGFR3(-/-)FGFR4(-/-) mice compared with wild-type mice (102.2 ± 14.8 vs. 266.0 ± 34.0 pmol/l; P = 0.001) as were the serum levels of FGF23. Administration of recombinant FGF23 had no effect on serum 1,25(OH)(2)Vitamin D(3) in the FGFR3(-/-)FGFR4(-/-) mice (173.4 ± 32.7 vs. 219.7 ± 56.5 pmol/l; vehicle vs. FGF23) while it reduced serum 1,25(OH)(2)Vitamin D(3) levels in wild-type mice. Administration of FGF23 to FGFR3(-/-)FGFR4(-/-) mice resulted in a decrease in serum parathyroid hormone (PTH) levels and an increase in serum phosphorus levels mediated by increased renal phosphate reabsorption. These data indicate that FGFR3 and 4 are the receptors that regulate serum 1,25(OH)(2)Vitamin D(3) levels in response to FGF23. In addition, when 1,25(OH)(2)Vitamin D(3) levels are not affected by FGF23, as in FGFR3(-/-)FGFR4(-/-) mice, a reduction in PTH can override the effects of FGF23 on renal phosphate transport.

Hedgehog-producing Cancer Cells Respond to and Require Autocrine Hedgehog Activity

Cancer Research. Jul, 2011  |  Pubmed ID: 21565978

A number of Smoothened (SMO) pathway antagonists are currently undergoing clinical trials as anticancer agents. These drugs are proposed to attenuate tumor growth solely through inhibition of Hedgehog (HH), which is produced in tumor cells but acts on tumor stromal cells. The pivotal argument underlying this model is that the growth-inhibitory properties of SMO antagonists on HH-producing cancer cells are due to their off-target effects. Here, we show that the tumorigenic properties of such lung cancer cells depend on their intrinsic level of HH activity. Notably, reducing HH signaling in these tumor cells decreases HH target gene expression. Taken together, these results question the dogma that autocrine HH signaling plays no role in HH-dependent cancers, and does so without using SMO antagonists.

Confocal Laser Endomicroscopy in Gastrointestinal Diseases

Journal of Biophotonics. Aug, 2011  |  Pubmed ID: 21567975

Confocal laser endomicroscopy (CLE) is a novel endoscopic technique permitting in vivo microscopy (optical biopsies) of the gastrointestinal mucosa. CLE has been studied in a multitude of diseases of the upper and lower gastrointestinal tract, including Barrett's esophagus, gastric inflammation and cancer, celiac disease, colorectal adenoma and carcinoma, and inflammatory bowel diseases. CLE has recently evolved and been studied for bile duct and liver imaging. CLE has shown overall high accuracy and enabled smart, targeted biopsies rather than untargeted sampling. Furthermore, the availability of real time microscopic information during endoscopy has immediate impact on therapeutic decisions and guides endoscopic interventions. CLE is also a unique tool for observation of (patho-)physiologic events in their natural environment (functional imaging) and has been linked to molecular imaging of gastrointestinal neoplasia in vivo, thereby broadening our understanding of mucosal pathology in clinical and basic science.

Thermodilution-derived Indices for Assessment of Left and Right Ventricular Cardiac Function in Normal and Impaired Cardiac Function

Critical Care Medicine. Sep, 2011  |  Pubmed ID: 21572331

The aim of this study was to assess whether thermodilution-derived parameters of right and left ventricular cardiac function (right ventricular ejection fraction, global ejection fraction, cardiac function index) are able to track changes of cardiac contractile function and whether they are influenced by substantial preload reduction.

Perceived Risk of Female Infidelity Moderates the Relationship Between Objective Risk of Female Infidelity and Sexual Coercion in Humans (Homo Sapiens)

Journal of Comparative Psychology (Washington, D.C. : 1983). Aug, 2011  |  Pubmed ID: 21574690

Female extrapair copulation (EPC) can be costly to a woman's long-term romantic partner. If a woman has copulated recently with a man other than her long-term partner, her reproductive tract may contain the sperm of both men, initiating sperm competition (whereby sperm from multiple males compete to fertilize an egg). Should the woman become pregnant, her long-term partner is at risk of cuckoldry-investing unwittingly in offspring to whom he is not genetically related. Previous research in humans (Homo sapiens) and in nonhuman animals suggests that males have evolved tactics such as partner-directed sexual coercion that reduce the risk of cuckoldry. The current research provides preliminary evidence that mated men (n = 223) at greater risk of partner EPC, measured as having spent a greater proportion of time apart from their partner since the couple's last in-pair copulation, more frequently perform partner-directed sexually coercive behaviors. This relationship is moderated, however, by men's perceived risk of partner EPC, such that the correlation between the proportion of time spent apart since last in-pair copulation and sexually coercive behaviors remains significant only for those men who perceive themselves to be at some risk of partner EPC. Discussion addresses limitations of this research and highlights directions for future research investigating the relationship between female EPC and men's partner-directed sexual coercion.

The Movement Disorder Society and Movement Disorders: a Modern History

Movement Disorders : Official Journal of the Movement Disorder Society. May, 2011  |  Pubmed ID: 21626540

The Movement Disorder Society (MDS) developed out of a merger with two short-lived organizations, the Movement Disorder Society, primarily organized to develop a journal for the subspecialty, and the International Society of Motor Disturbances, primarily organized to develop international congresses. The formal merger of the Movement Disorder Society and the International Society of Motor Disturbances into the Movement Disorder Society took place at the 2nd International Congress of Movement Disorders in Munich, Germany, in June 1992. Whereas the journal, Movement Disorders, and the annual International Congress of Parkinson's Disease and Movement Disorders remain the anchors of the society, the goals now include the development of regional symposia, regional sections, Web-based educational programs, and outreach efforts to include young investigators, wide international membership, and inclusion of non-neurologists, including basic scientists, neurosurgeons, and nonphysician health professionals. Movement Disorders has a continuingly growing subscribership and rising impact factor.

Validity of Diagnostic Codes and Liver-related Laboratory Abnormalities to Identify Hepatic Decompensation Events in the Veterans Aging Cohort Study

Pharmacoepidemiology and Drug Safety. Jul, 2011  |  Pubmed ID: 21626605

The absence of validated methods to identify hepatic decompensation in cohort studies has prevented a full understanding of the natural history of chronic liver diseases and impact of medications on this outcome. We determined the ability of diagnostic codes and liver-related laboratory abnormalities to identify hepatic decompensation events within the Veterans Aging Cohort Study (VACS).

Colonic Polyposis and Neoplasia in Cowden Syndrome

Mayo Clinic Proceedings. Mayo Clinic. Jun, 2011  |  Pubmed ID: 21628613

To identify and describe the frequency, histologic features, and clinical outcome of colon polyposis and neoplasia in Cowden syndrome--a rare familial hamartoma tumor syndrome associated with mutations in the PTEN gene.

An Update Expert Opinion on Management and Research Strategies in Parkinson's Disease Psychosis

Expert Opinion on Pharmacotherapy. Sep, 2011  |  Pubmed ID: 21635198

INTRODUCTION: Psychosis, a frequent complication in Parkinson's disease (PD), contributes significantly to morbidity, mortality, nursing-home placement and quality of life. Medication side effects, issues of trial design and negative outcomes have limited clinical advances of new treatments for PD psychosis. Evidence-based medicine maintains clozapine as the most effective antipsychotic in PD without motor worsening, despite risk of agranulocytosis. Safe, effective treatments that improve psychosis without exacerbating parkinsonism are urgently needed. AREAS COVERED: This article reviews the: i) phenomenology of PD psychosis, ii) pharmacological rationale for antipsychotics in PD; iii) clinical trials of antipsychotics in PD; iv) novel research strategies such as neuroimaging, genetics and animal models; and v) associated challenges in studying and treating PD psychosis. Preparation of this review included an extensive literature search using PubMed. EXPERT OPINION: Management of PD psychosis is complex. Challenges pertaining to study design, rating scales, subject recruitment and completion have limited PD psychosis treatment trials. Novel research strategies focus on nondopaminergic systems and incorporate neuroimaging, genetic associations and animal models. These strategies also have challenges but have the potential to enhance our understanding of PD psychosis and advance the development of agents that can ultimately be tested in well-designed, randomized, controlled trials.

A Compact Electron Cyclotron Resonance Proton Source for the Paul Scherrer Institute's Proton Accelerator Facility

The Review of Scientific Instruments. May, 2011  |  Pubmed ID: 21639497

A compact electron cyclotron resonance proton source has been developed and installed recently at the Paul Scherrer Institute's high intensity proton accelerator. Operation at the ion source test stand and the accelerator demonstrates a high reliability and stability of the new source. When operated at a 10-12  mA net proton current the lifetime of the source exceeds 2000 h. The essential development steps towards the observed performance are described.

Social Class Rank, Threat Vigilance, and Hostile Reactivity

Personality & Social Psychology Bulletin. Oct, 2011  |  Pubmed ID: 21653579

Lower-class individuals, because of their lower rank in society, are theorized to be more vigilant to social threats relative to their high-ranking upper-class counterparts. This class-related vigilance to threat, the authors predicted, would shape the emotional content of social interactions in systematic ways. In Study 1, participants engaged in a teasing interaction with a close friend. Lower-class participants--measured in terms of social class rank in society and within the friendship--more accurately tracked the hostile emotions of their friend. As a result, lower-class individuals experienced more hostile emotion contagion relative to upper-class participants. In Study 2, lower-class participants manipulated to experience lower subjective socioeconomic rank showed more hostile reactivity to ambiguous social scenarios relative to upper-class participants and to lower-class participants experiencing elevated socioeconomic rank. The results suggest that class affects expectations, perception, and experience of hostile emotion, particularly in situations in which lower-class individuals perceive their subordinate rank.

Heart-lung Interactions Measured by Electrical Impedance Tomography

Critical Care Medicine. Sep, 2011  |  Pubmed ID: 21666450

The clinical value of stroke volume variations to assess intravascular fluid status in critically ill patients is well known. Electrical impedance tomography is a noninvasive monitoring technology that has been primarily used to assess ventilation. We investigated the potential of electrical impedance tomography to measure left ventricular stroke volume variation as an expression of heart-lung interactions. The objective of this study was thus to determine in a set of different hemodynamic conditions whether stroke volume variation measured by electrical impedance tomography correlates with those derived from an aortic ultrasonic flow probe and arterial pulse contour analysis.

Effectiveness of a Mass Media Campaign in Promoting HIV Testing Information Seeking Among African American Women

Journal of Health Communication. Oct, 2011  |  Pubmed ID: 21707409

"Take Charge. Take the Test." (TCTT), a media campaign promoting HIV testing among African American women, was piloted in Cleveland and Philadelphia from October 2006 to October 2007. This study assesses TCTT's effectiveness in promoting HIV testing information seeking among target audiences in each pilot city. The authors analyzed data on telephone hotlines promoted by the campaign and the www.hivtest.org Web site to examine trends in hotline calls and testing location searches before, during, and after the campaign. Cleveland hotline data were available from October 1, 2005, through February 28, 2008, for a total of 29 months (N = 126 weeks). Philadelphia hotline data were available from May 1, 2006, through February 28, 2008, for a total of 22 months (N = 96 weeks). The authors assessed the relation between market-level measures of the campaign's advertising activities and trends in hotline call volume and testing location searches. They found a significant relation between measures of TCTT advertising and hotline calls. Specifically, they found that increases in advertising gross ratings points were associated with increases in call volume, controlling for caller demographics and geographic location. The campaign had similar effects on HIV testing location searches. Overall, it appears the campaign generated significant increases in HIV information seeking. Results are consistent with other studies that have evaluated the effects of media campaigns on similar forms of information seeking. This study illustrates useful methods for evaluating campaign effects on information seeking with data on media implementation, hotline calls, and zip code-based searches for testing locations.

Effect of Expanded HIV Testing Programs on the Status of Newly Diagnosed HIV-infected Patients in Two Veterans Health Administration Facilities: 1999-2009

Journal of Acquired Immune Deficiency Syndromes (1999). Jun, 2011  |  Pubmed ID: 21709450

Regulation of Ingestive Behaviors in the Rat by GSK1521498, a Novel Micro-opioid Receptor-selective Inverse Agonist

The Journal of Pharmacology and Experimental Therapeutics. Oct, 2011  |  Pubmed ID: 21712426

μ-Opioid receptor (MOR) agonism induces palatable food consumption principally through modulation of the rewarding properties of food. N-{[3,5-difluoro-3'-(1H-1,2,4-triazol-3-yl)-4-biphenylyl]methyl}-2,3-dihydro-1H-inden-2-amine (GSK1521498) is a novel opioid receptor inverse agonist that, on the basis of in vitro affinity assays, is greater than 10- or 50-fold selective for human or rat MOR, respectively, compared with κ-opioid receptors (KOR) and δ-opioid receptors (DOR). Likewise, preferential MOR occupancy versus KOR and DOR was observed by autoradiography in brain slices from Long Evans rats dosed orally with the drug. GSK1521498 suppressed nocturnal food consumption of standard or palatable chow in lean and diet-induced obese (DIO) Long Evans rats. Both the dose-response relationship and time course of efficacy in lean rats fed palatable chow correlated with μ receptor occupancy and the plasma concentration profile of the drug. Chronic oral administration of GSK1521498 induced body weight loss in DIO rats, which comprised fat mass reduction. The reduction in body weight was equivalent to the cumulative reduction in food consumption; thus, the effect of GSK1521498 on body weight is related to inhibition of food consumption. GSK1521498 suppressed the preference for sucrose-containing solutions in lean rats. In operant response models also using lean rats, GSK1521498 reduced the reinforcement efficacy of palatable food reward and enhanced satiety. In conclusion, GSK1521498 is a potent, MOR-selective inverse agonist that modulates the hedonic aspects of ingestion and, therefore, could represent a pharmacological treatment for obesity and binge-eating disorders.

The Risk of Incident Coronary Heart Disease Among Veterans with and Without HIV and Hepatitis C

Circulation. Cardiovascular Quality and Outcomes. Jul, 2011  |  Pubmed ID: 21712519

Whether hepatitis C virus (HCV) confers additional coronary heart disease (CHD) risk among human immunodeficiency virus (HIV) infected individuals is unclear. Without appropriate adjustment for antiretroviral therapy, CD4 count, and HIV-1 RNA and substantially different mortality rates among those with and without HIV and HCV infection, the association between HIV, HCV, and CHD may be obscured.

A Comprehensive Review of Predictive and Prognostic Composite Factors Implicated in the Heterogeneity of Treatment Response and Outcome Across Disease Areas

International Journal of Clinical Practice. Aug, 2011  |  Pubmed ID: 21718398

To assess and present the current body of evidence regarding composite measures associated with differential treatment response or outcome as a result of patient heterogeneity and to evaluate their consistency across disease areas.

Symptoms of Depression in a Minority Population of Women from an Urban Obstetrics and Gynecology Clinic

Gender Medicine. Oct, 2011  |  Pubmed ID: 21723204

The aim of this exploratory study was to determine and compare the rates of depressive symptoms across 3 groups of African-American and Hispanic pregnant, postpartum, and nonperipartum gynecology patients in a hospital-based urban outpatient obstetrics and gynecology clinic.

Weight Loss Intervention for People with Serious Mental Illness: a Randomized Controlled Trial of the RENEW Program

Psychiatric Services (Washington, D.C.). Jul, 2011  |  Pubmed ID: 21724796

This study assessed phases one and two of a three-phase weight-loss program called RENEW--Recovering Energy Through Nutrition and Exercise for Weight Loss--among individuals with serious mental illness at four mental health centers. RENEW provides meal replacements twice daily and intensive instruction in nutrition and meal preparation, exercise, and goal setting for three months followed by three months of maintenance.

Biomechanical Remodeling of the Microenvironment by Stromal Caveolin-1 Favors Tumor Invasion and Metastasis

Cell. Jul, 2011  |  Pubmed ID: 21729786

Mechanotransduction is a key determinant of tissue homeostasis and tumor progression. It is driven by intercellular adhesions, cell contractility, and forces generated within the microenvironment and is dependent on extracellular matrix composition, organization, and compliance. We show that caveolin-1 (Cav1) favors cell elongation in three-dimensional cultures and promotes Rho- and force-dependent contraction, matrix alignment, and microenvironment stiffening through regulation of p190RhoGAP. In turn, microenvironment remodeling by Cav1 fibroblasts forces cell elongation. Cav1-deficient mice have disorganized stromal tissue architecture. Stroma associated with human carcinomas and melanoma metastases is enriched in Cav1-expressing carcinoma-associated fibroblasts (CAFs). Cav1 expression in breast CAFs correlates with low survival, and Cav1 depletion in CAFs decreases CAF contractility. Consistently, fibroblast expression of Cav1, through p190RhoGAP regulation, favors directional migration and invasiveness of carcinoma cells in vitro. In vivo, stromal Cav1 remodels peri- and intratumoral microenvironments to facilitate tumor invasion, correlating with increased metastatic potency. Thus, Cav1 modulates tissue responses through force-dependent architectural regulation of the microenvironment.

Effect of Acene Length on Electronic Properties in 5-, 6-, and 7-ringed Heteroacenes

Advanced Materials (Deerfield Beach, Fla.). Aug, 2011  |  Pubmed ID: 21732562

Health-related Quality-of-life Scales in Parkinson's Disease: Critique and Recommendations

Movement Disorders : Official Journal of the Movement Disorder Society. Nov, 2011  |  Pubmed ID: 21735480

Health-related quality of life is an important patient-reported outcome used in intervention trials and for monitoring the consequences of health status on physical, mental, and social domains. Parkinson's disease is a complex disorder that strongly affects patients' quality of life. Several health-related quality of life tools have been used in Parkinson's disease. A Movement Disorder Society Task Force was commissioned to rate the psychometric quality of available health-related quality of life scales as applied to Parkinson's disease. Following the methodology adopted by previous work of the Movement Disorder Society Task Force, a review of generic and specific health-related quality of life scales applied in studies on Parkinson's disease was completed. Considering the scales from 3 perspectives-use in Parkinson's disease, use by multiple research groups, and clinimetric properties-a final classification as "recommended," "suggested," or "listed" was applied to each reviewed instrument. Four generic scales (EuroQoL, Nottingham Health Profile, 36-Item Short-Form Health Survey, and Sickness Impact Profile) and 5 specific scales (39-Item Parkinson's Disease Questionnaire, Parkinson's Disease Questionnaire Short Form, Parkinson's Disease Quality of Life Questionnaire, Parkinson's Impact Scale, and Scales for Outcomes in Parkinson's Disease-Psychosocial) reached the level of "recommended." The 39-item Parkinson's Disease Questionnaire is the most thoroughly tested and applied questionnaire. Three other generic measures (Quality of Life Questionnaire 15D, Schedule for the Evaluation of Individual Quality of Life-Direct Weighting, and World Health Organization Quality of Life Assessment Short Version) and the specific Parkinson's Disease Quality of Life Scale are "suggested." With a little additional effort in completing the stipulated requirements, they could reach the "recommended" level. At present there is a wide variety of health-related quality of life measures for application in the Parkinson's disease setting, and the task force does not recommend the development of a new scale. Selection of the most appropriate instrument for a particular objective requires consideration of the characteristics of each scale and the goals of the assessment.

Applicability of the Assessment of Chronic Illness Care (ACIC) Instrument in Germany Resulting in a New Questionnaire: Questionnaire of Chronic Illness Care in Primary Care

BMC Health Services Research. 2011  |  Pubmed ID: 21736721

The Chronic Care Model (CCM) is an evidence based, population based approach to improve care for people with chronic conditions. The Assessment of Chronic Illness Care (ACIC) instrument is widely used to measure to what extent within a healthcare system the CCM is implemented. The aim of this study was to translate and culturally adapt the ACIC Instrument for the German healthcare system.

Pregnane X Receptor Activation Induces FGF19-dependent Tumor Aggressiveness in Humans and Mice

The Journal of Clinical Investigation. Aug, 2011  |  Pubmed ID: 21747170

The nuclear receptor pregnane X receptor (PXR) is activated by a range of xenochemicals, including chemotherapeutic drugs, and has been suggested to play a role in the development of tumor cell resistance to anticancer drugs. PXR also has been implicated as a regulator of the growth and apoptosis of colon tumors. Here, we have used a xenograft model of colon cancer to define a molecular mechanism that might underlie PXR-driven colon tumor growth and malignancy. Activation of PXR was found to be sufficient to enhance the neoplastic characteristics, including cell growth, invasion, and metastasis, of both human colon tumor cell lines and primary human colon cancer tissue xenografted into immunodeficient mice. Furthermore, we were able to show that this PXR-mediated phenotype required FGF19 signaling. PXR bound to the FGF19 promoter in both human colon tumor cells and "normal" intestinal crypt cells. However, while both cell types proliferated in response to PXR ligands, the FGF19 promoter was activated by PXR only in cancer cells. Taken together, these data indicate that colon cancer growth in the presence of a specific PXR ligand results from tumor-specific induction of FGF19. These observations may lead to improved therapeutic regimens for colon carcinomas.

Visual Plus Nonvisual Hallucinations in Parkinson's Disease: Development and Evolution over 10 Years

Movement Disorders : Official Journal of the Movement Disorder Society. Oct, 2011  |  Pubmed ID: 21755536

The objective of the study was to assess the development and evolution of visual and nonvisual hallucinations in patients with Parkinson's disease over 10 years. Hallucinations increase over time, but minimal attention has been placed on nonvisual domains. We studied 60 patients with Parkinson's disease who had never hallucinated at baseline and followed them over 10 years. The Rush Hallucination Inventory monitored frequency and type (visual, auditory, tactile, olfactory) of hallucinations at baseline and after 0.5, 1.5, 4, 6, and 10 years. Descriptive statistics were applied, and general estimating equation modeling assessed longitudinal risks. Over 10 years, visual hallucinations were endorsed by patients more frequently than other sensory modalities. Whereas isolated visual hallucinations dominated the early hallucination profile, visual plus nonvisual hallucinations accounted for progressively higher proportions of hallucinators over 10 years: 0.5 years, 0%; 4 years, 26%; 6 years, 47%; 10 years, 60% (odds ratio, 1.17; confidence interval, 1.01-1.37; P = .04). Once visual plus nonvisual hallucinations developed, the risk of continuing to have multidomain hallucinations was high (odds ratio, 3.67; confidence interval, 1.13-11.93; P = .03). Hallucination severity was highly associated with current visual plus nonvisual hallucinations (odds ratio, 4.06; confidence interval, 2.93-5.61; P < .0001) and the continuation of multidomain hallucinations (odds ratio, 1.58; confidence interval, 1.12-2.24; P = .01). Whereas visual hallucinations in isolation are classic in Parkinson's disease, nonvisual hallucinations emerge over time, and the combination of visual with nonvisual hallucinations predominates in late Parkinson's disease. To capture the breadth and severity of hallucinations in chronically hallucinating patients with Parkinson's disease, screening inventories and practice-based interviews must include questions on both visual and nonvisual components.

Options for Hearing Rehabilitation in Children with Cochleovestibular Nerve Dysplasia

Cochlear Implants International. May, 2011  |  Pubmed ID: 21756490

Testing the Predictors of Boredom at School: Development and Validation of the Precursors to Boredom Scales

The British Journal of Educational Psychology. Sep, 2011  |  Pubmed ID: 21770913

BACKGROUND. Boredom has been found to be an important emotion for students' learning processes and achievement outcomes; however, the precursors of this emotion remain largely unexplored. AIM. In the current study, scales assessing the precursors to boredom in academic achievement settings were developed and tested. SAMPLE. Participants were 1,380 grade 5-10 students in mathematics classes. METHOD. The Precursors to Boredom Scales were tested for structural and convergent validity with multi-level confirmatory factor analyses (ML-CFA), and differences in the perception of the precursors of boredom due to gender were investigated. RESULTS. The first ML-CFA found support for the structural validity of the Precursors to Boredom Scales. In a second ML-CFA, the newly developed boredom scales showed good convergent validity with several key aspects of instructional quality. Finally, the results supported previous research that found no gender differences in academic self-concept and interest. CONCLUSION. The precursors contained in our scales are empirically separable. Implications of the current findings for research on boredom among students are discussed.

In Vivo Real-time Imaging of the Liver with Confocal Endomicroscopy Permits Visualization of the Temporospatial Patterns of Hepatocyte Apoptosis

American Journal of Physiology. Gastrointestinal and Liver Physiology. Nov, 2011  |  Pubmed ID: 21778462

Apoptosis is a dynamic process of programmed cell death and is involved in multiple diseases. However, its mechanisms and sequence of events are still incompletely understood, partly because of the inability to visualize single cells continuously in vivo. The aim of the present study was to monitor hepatocyte apoptosis with confocal endomicroscopy in living rodents. In 73 anaesthetized mice, apoptotic liver injury was induced by injection of the CD95-agonistic antibody Jo2. Individual hepatocytes were followed for up to 240 min with a handheld confocal probe (FIVE1; Optiscan) providing 0.7 μm resolution (1,000-fold magnification). Different fluorescence staining protocols were used for cellular staining, vascular and cellular barrier function imaging, and caspase activation visualization. The time course of apoptosis could be visualized in vivo while liver perfusion and tissue integrity were maintained. In contrast to most ex vivo studies, initial cell swelling was observed that coincided with early defects in barrier function of sinusoids and hepatocytes. Cytoplasmic vesicle formation, nuclear condensation, cellular disintegration, and macrophage infiltration were captured sequentially. Labeling of caspases allowed molecular imaging. Our study allowed for the first time to continuously follow distinct morphological, functional, and molecular features of apoptosis in a solid organ in vivo and at high resolution. Intravital confocal microscopy may be a valuable tool to study the effects of therapeutic intervention on apoptosis in animal models and humans.

Wearing-off Scales in Parkinson's Disease: Critique and Recommendations

Movement Disorders : Official Journal of the Movement Disorder Society. Oct, 2011  |  Pubmed ID: 21780180

Wearing-off occurs in the majority of patients with Parkinson's disease after a few years of dopaminergic therapy. Because a variety of scales have been used to estimate wearing-off, the Movement Disorder Society commissioned a task force to assess their clinimetric properties. A systematic review was conducted to identify wearing-off scales that have either been validated or used in Parkinson's patients. A scale was designated "Recommended" if it had been used in clinical studies beyond the group that developed it, if it had been specifically used in Parkinson's disease reports, and if clinimetric studies had established that it is valid, reliable, and sensitive. "Suggested" scales met 2 of the above criteria, and those meeting 1 were "Listed." We identified 3 diagnostic and 4 severity rating scales for wearing-off quantification. Two questionnaires met the criteria to be Recommended for diagnostic screening (questionnaires for 19 and 9 items), and 1 was Suggested (questionnaire for 32 items). Only the patient diaries were Recommended to assess wearing-off severity, with the caveat of relatively limited knowledge of validity. Among the other severity assessment tools, the Unified Parkinson Disease Rating Scale version 3 and the version revised from the Movement Disorders Society were classified as Suggested, whereas the Treatment Response Scale was Listed.

Palliation of Painful Metastatic Disease Involving Bone with Imaging-guided Treatment: Comparison of Patients' Immediate Response to Radiofrequency Ablation and Cryoablation

AJR. American Journal of Roentgenology. Aug, 2011  |  Pubmed ID: 21785102

The purpose of this article was to compare periprocedural analgesic requirements and hospital length of stay for treatment of patients with painful metastatic tumors involving bone using either percutaneous radiofrequency ablation (RFA) or cryoablation.

German Network for Congenital Uro-rectal Malformations: First Evaluation and Interpretation of Postoperative Urological Complications in Anorectal Malformations

Pediatric Surgery International. Oct, 2011  |  Pubmed ID: 21792651

The aim of the German Network for Congenital Uro-REctal Malformations is to collect data of affected patients with anorectal malformation (ARM) or extrophy-epispadias complex, and to investigate molecular causes, clinical implications, and psychosocial outcome. The current issue was to assess the postoperative sequelae related to lower urinary tract dysfunction in patients with ARM.

A Quantitative Real-time PCR Approach for the Detection and Characterization of Endothelial Cells in Whole Blood

Annals of Biomedical Engineering. Oct, 2011  |  Pubmed ID: 21796502

Pathological inflammation and endothelial dysfunction in atherosclerosis causes endothelial cell detachment from affected vasculature giving rise to circulating endothelial cells (CECs). A blood-based assay that can detect and characterize CECs in atherosclerosis could serve as a valuable diagnostic. Thus, we sought to develop a prototypic assay that detects and characterizes the inflammatory state of endothelial cells present in blood. For this purpose, we spiked resting and inflamed human umbilical vein endothelial cells (HUVEC) into separate samples of whole blood. RNA was harvested and analyzed via quantitative real-time PCR (qPCR) using melanoma cell adhesion molecule (MCAM), as an endothelial marker, and vascular cell adhesion molecule (VCAM-1), which is increased on inflamed endothelium. We found that MCAM mRNA levels correlated with the number of HUVEC spiked into the blood. VCAM-1 mRNA levels were elevated, and correlated with the number of HUVEC, in blood spiked with inflamed HUVEC but not in blood spiked with resting HUVEC. VCAM-1 and MCAM mRNA levels were converted into numerical indices that indicate the inflammatory state of the HUVEC. Combined, the blood spiking studies demonstrate that a VCAM-1/MCAM qPCR assay can successfully detect inflamed endothelial cells in whole blood thus providing proof-of-concept for a diagnostic based on a coupled-phenotypic qPCR assay.

[Granular-cell Tumor (Abrikossoff's Tumor): Precise Preoperative Diagnosis is Crucial when for Minimally-invasive Resection]

Deutsche Medizinische Wochenschrift (1946). Aug, 2011  |  Pubmed ID: 21809253

A 38-year-old man was referred to a gastroenterologist because of thoracic pain and dysphagia of uncertain cause.

Haemodynamics and Cardiac Function During Robotic-assisted Laparoscopic Prostatectomy in Steep Trendelenburg Position

The International Journal of Medical Robotics + Computer Assisted Surgery : MRCAS. Dec, 2011  |  Pubmed ID: 21815239

Robotic-assisted laparoscopic prostatectomy (RALP) is usually performed in steep Trendelenburg position, which can be associated with cardiac impairment due to positioning and capnoperitoneum. This study investigated haemodynamic consequences and cardiac function in this type of surgery and evaluated the hypothesis that steep Trendelenburg position and capnoperitoneum results in haemodynamic and ventricular impairment.

Inhibitors of SARS-CoV Entry--identification Using an Internally-controlled Dual Envelope Pseudovirion Assay

Antiviral Research. Nov, 2011  |  Pubmed ID: 21820471

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) emerged as the causal agent of an endemic atypical pneumonia, infecting thousands of people worldwide. Although a number of promising potential vaccines and therapeutic agents for SARS-CoV have been described, no effective antiviral drug against SARS-CoV is currently available. The intricate, sequential nature of the viral entry process provides multiple valid targets for drug development. Here, we describe a rapid and safe cell-based high-throughput screening system, dual envelope pseudovirion (DEP) assay, for specifically screening inhibitors of viral entry. The assay system employs a novel dual envelope strategy, using lentiviral pseudovirions as targets whose entry is driven by the SARS-CoV Spike glycoprotein. A second, unrelated viral envelope is used as an internal control to reduce the number of false positives. As an example of the power of this assay a class of inhibitors is reported with the potential to inhibit SARS-CoV at two steps of the replication cycle, viral entry and particle assembly. This assay system can be easily adapted to screen entry inhibitors against other viruses with the careful selection of matching partner virus envelopes.

Pain Acceptance, Hope, and Optimism: Relationships to Pain and Adjustment in Patients with Chronic Musculoskeletal Pain

The Journal of Pain : Official Journal of the American Pain Society. Nov, 2011  |  Pubmed ID: 21820969

There is growing interest in the role that positive aspects of psychological adjustment, such as pain acceptance, hope, and optimism, may play in explaining adjustment in persons suffering from persistent pain. This study conducted in obese patients with persistent musculoskeletal pain (N = 89) examined the degree to which pain acceptance and hope explained pain intensity, pain unpleasantness, psychological distress, and pain-related disability, after controlling for the effects of optimism. In correlational analyses, pain acceptance and optimism were associated with psychological distress and pain disability with hope being related to only psychological distress. Pain acceptance, optimism, and hope were not significantly associated with pain. Hierarchical linear regression (HLR) analyses found that pain acceptance remained a significant predictor of psychological distress and pain disability after controlling for optimism, demographic, and medical variables. HLR analyses found that hope was not a significant predictor of psychological distress after controlling for optimism, pain acceptance, and demographic and medical variables. The results of this study are important because they indicate that pain acceptance, hope, and optimism are all related to pain adjustment. They also highlight the importance of controlling for optimism when examining the effects of pain acceptance and hope on pain adjustment. PERSPECTIVE: In a sample of obese patients with persistent musculoskeletal pain, pain acceptance was a significant predictor of psychological distress and pain disability even after controlling for optimism, demographic, and medical variables. These results add to the growing literature on the importance of pain acceptance in understanding adjustment to persistent pain.

Molecular Dissection of Cis-regulatory Modules at the Drosophila Bithorax Complex Reveals Critical Transcription Factor Signature Motifs

Developmental Biology. Nov, 2011  |  Pubmed ID: 21821017

At the Drosophila melanogaster bithorax complex (BX-C) over 330kb of intergenic DNA is responsible for directing the transcription of just three homeotic (Hox) genes during embryonic development. A number of distinct enhancer cis-regulatory modules (CRMs) are responsible for controlling the specific expression patterns of the Hox genes in the BX-C. While it has proven possible to identify orthologs of known BX-C CRMs in different Drosophila species using overall sequence conservation, this approach has not proven sufficiently effective for identifying novel CRMs or defining the key functional sequences within enhancer CRMs. Here we demonstrate that the specific spatial clustering of transcription factor (TF) binding sites is important for BX-C enhancer activity. A bioinformatic search for combinations of putative TF binding sites in the BX-C suggests that simple clustering of binding sites is frequently not indicative of enhancer activity. However, through molecular dissection and evolutionary comparison across the Drosophila genus we discovered that specific TF binding site clustering patterns are an important feature of three known BX-C enhancers. Sub-regions of the defined IAB5 and IAB7b enhancers were both found to contain an evolutionarily conserved signature motif of clustered TF binding sites which is critical for the functional activity of the enhancers. Together, these results indicate that the spatial organization of specific activator and repressor binding sites within BX-C enhancers is of greater importance than overall sequence conservation and is indicative of enhancer functional activity.

Patient and Provider Characteristics Associated with the Decision of HIV Coinfected Patients to Start Hepatitis C Treatment

AIDS Patient Care and STDs. Sep, 2011  |  Pubmed ID: 21823907

Hepatitis C (HCV) and HIV coinfection is common and liver disease is a leading cause of morbidity and mortality among coinfected patients. Despite advances in HCV treatment, few HIV coinfected patients actually initiate treatment. We examined patient and provider characteristics associated with a patient's decision to accept or refuse HCV treatment once offered. We conducted patient chart abstraction and surveys with 127 HIV coinfected patients who were offered HCV treatment by their provider and surveys of their HCV care providers at three HIV clinics. Participants were mostly male (87%), minority (66%), and had a history of injection drug use (60%). Most had been diagnosed with HIV for several years (X=13.7 years) and reported HIV transmission through unprotected sex (47%). Of the 127 patients, 79 accepted treatment. In multivariate analysis, patients who had a CD4 greater than 200 cells/mm(3) and a provider with more confidence about HCV treatment were more likely to accept the recommendation to start treatment; younger age was marginally associated with treatment acceptance. In bivariate analysis, added correlates of treatment acceptance included male gender, no recent drug use, and several provider attitudes regarding treatment and philosophy about determination of patient treatment readiness. Patient and provider characteristics are important when understanding a patient's decision to start or defer HCV treatment. Further research is needed to better understand barriers to treatment uptake as new and more effective HCV treatments will soon be available.

Differential Gene Expression in the Siphonophore Nanomia Bijuga (Cnidaria) Assessed with Multiple Next-generation Sequencing Workflows

PloS One. 2011  |  Pubmed ID: 21829563

We investigated differential gene expression between functionally specialized feeding polyps and swimming medusae in the siphonophore Nanomia bijuga (Cnidaria) with a hybrid long-read/short-read sequencing strategy. We assembled a set of partial gene reference sequences from long-read data (Roche 454), and generated short-read sequences from replicated tissue samples that were mapped to the references to quantify expression. We collected and compared expression data with three short-read expression workflows that differ in sample preparation, sequencing technology, and mapping tools. These workflows were Illumina mRNA-Seq, which generates sequence reads from random locations along each transcript, and two tag-based approaches, SOLiD SAGE and Helicos DGE, which generate reads from particular tag sites. Differences in expression results across workflows were mostly due to the differential impact of missing data in the partial reference sequences. When all 454-derived gene reference sequences were considered, Illumina mRNA-Seq detected more than twice as many differentially expressed (DE) reference sequences as the tag-based workflows. This discrepancy was largely due to missing tag sites in the partial reference that led to false negatives in the tag-based workflows. When only the subset of reference sequences that unambiguously have tag sites was considered, we found broad congruence across workflows, and they all identified a similar set of DE sequences. Our results are promising in several regards for gene expression studies in non-model organisms. First, we demonstrate that a hybrid long-read/short-read sequencing strategy is an effective way to collect gene expression data when an annotated genome sequence is not available. Second, our replicated sampling indicates that expression profiles are highly consistent across field-collected animals in this case. Third, the impacts of partial reference sequences on the ability to detect DE can be mitigated through workflow choice and deeper reference sequencing.

Comparison of Coil Designs for Peripheral Magnetic Muscle Stimulation

Journal of Neural Engineering. Oct, 2011  |  Pubmed ID: 21832812

The recent application of magnetic stimulation in rehabilitation is often said to solve key drawbacks of the established electrical method. Magnetic fields cause less pain, allow principally a better penetration of inhomogeneous biologic tissue and do not require skin contact. However, in most studies the evoked muscle force has been disappointing. In this paper, a comparison of a classical round circular geometry, a commercial muscle-stimulation coil and a novel design is presented, with special emphasis on the physical field properties. These systems show markedly different force responses for the same magnetic energy and highlight the enormous potential of different coil geometries. The new design resulted in a slope of the force recruiting curve being more than two and a half times higher than the other coils. The data were analyzed with respect to the underlying physical causes and field conditions. After a parameter-extraction approach, the results for the three coils span a two-dimensional space with clearly distinguishable degrees of freedom, which can be manipulated nearly separately and reflect the two main features of a field; the peak amplitude and its decay with the distance.

Current and Future Use of Genomics Data in Toxicology: Opportunities and Challenges for Regulatory Applications

Regulatory Toxicology and Pharmacology : RTP. Nov, 2011  |  Pubmed ID: 21840362

Toxicogenomics is the application of toxicology, genetics, molecular biology and environmental health to describe the response of organisms to environmental stimuli. The field of toxicogenomics has developed over the past 15 years mainly due to advances in toxicology, molecular genetics and cell biology. Its prospective use to resolve crucial data gaps and data inconsistencies could improve risk assessment by providing additional data to increase the understanding of mechanisms and modes of action (MOA) and enhance the reliability of dose-response extrapolation. Thus, toxicogenomics holds promise for advancing the scientific basis of risk assessments. However, one of the current issues is how genomic/transcriptional data is being used to further describe a MOA for oncogenicity and, in turn, its potential uses in cancer risk assessment. This commentary identifies how toxicogenomics could be used on a case by case basis to add information to a MOA addressing both the opportunities and challenges this technology holds. In addition, some pitfalls to avoid in the generation and interpretation of toxicogenomic data and validation issues that need to be addressed before toxicogenomics can be used in the risk assessment process and regulatory decisions are discussed.

Parvovirus B19-induced Type II Mixed Cryoglobulinemia

The American Journal of Medicine. Sep, 2011  |  Pubmed ID: 21854885

Heterogeneity of Auditory Verbal Working Memory in Schizophrenia

Journal of Abnormal Psychology. Feb, 2011  |  Pubmed ID: 21319926

The heterogeneity of schizophrenia remains an obstacle for understanding its pathophysiology. Studies using a tone discrimination screening test to classify patients have found evidence for 2 subgroups having either a specific deficit in verbal working memory (WM) or deficits in both verbal and nonverbal memory. This study aimed to (a) replicate in larger samples differences between these subgroups in auditory verbal WM; (b) evaluate their performance on tests of explicit memory and sustained attention; (c) determine the relation of verbal WM deficits to auditory hallucinations and other symptoms; and (d) examine medication effects. The verbal WM and tone discrimination performance did not differ between medicated (n = 45) and unmedicated (n = 38) patients. Patients with schizophrenia who passed the tone screening test (discriminators; n = 60) were compared with those who did not (nondiscriminators; n = 23) and healthy controls (n = 47). The discriminator subgroup showed poorer verbal WM than did controls and a deficit in verbal but not visual memory on the Wechsler Memory Scale-Revised (Wechsler, 1987), whereas the nondiscriminator subgroup showed overall poorer performance on both verbal and nonverbal tests and a marked deficit in sustained attention. Verbal WM deficits in discriminators were correlated with auditory hallucinations but not with negative symptoms. The results are consistent with a verbal memory deficit in a subgroup of schizophrenia having intact auditory perception, which may stem from dysfunction of language-related cortical regions, and a more generalized cognitive deficit in a subgroup having auditory perceptual and attentional dysfunction.

Idiopathic Itch, Rash, and Urticaria/angioedema Merit Serum Vitamin D Evaluation: a Descriptive Case Series

The West Virginia Medical Journal. Jan-Feb, 2011  |  Pubmed ID: 21322467

Vitamin D insufficiency is epidemic. Rarely are cutaneous consequences attributed to low vitamin D.

Changes in Forest Productivity Across Alaska Consistent with Biome Shift

Ecology Letters. Apr, 2011  |  Pubmed ID: 21332901

Global vegetation models predict that boreal forests are particularly sensitive to a biome shift during the 21st century. This shift would manifest itself first at the biome's margins, with evergreen forest expanding into current tundra while being replaced by grasslands or temperate forest at the biome's southern edge. We evaluated changes in forest productivity since 1982 across boreal Alaska by linking satellite estimates of primary productivity and a large tree-ring data set. Trends in both records show consistent growth increases at the boreal-tundra ecotones that contrast with drought-induced productivity declines throughout interior Alaska. These patterns support the hypothesized effects of an initiating biome shift. Ultimately, tree dispersal rates, habitat availability and the rate of future climate change, and how it changes disturbance regimes, are expected to determine where the boreal biome will undergo a gradual geographic range shift, and where a more rapid decline.

Carbon Tube Electrodes for Electrocardiography-gated Cardiac Multimodality Imaging in Mice

Journal of the American Association for Laboratory Animal Science : JAALAS. Jan, 2011  |  Pubmed ID: 21333165

This report describes a simple design of noninvasive carbon tube electrodes that facilitates electrocardiography (ECG) in mice during cardiac multimodality preclinical imaging. Both forepaws and the left hindpaw, covered by conductive gel, of mice were placed into the openings of small carbon tubes. Cardiac ECG-gated single-photon emission CT, X-ray CT, and MRI were tested (n = 60) in 20 mice. For all applications, electrodes were used in a warmed multimodality imaging cell. A heart rate of 563 ± 48 bpm was recorded from anesthetized mice regardless of the imaging technique used, with acquisition times ranging from 1 to 2 h.

Overturning Indolyne Regioselectivities and Synthesis of Indolactam V

Journal of the American Chemical Society. Mar, 2011  |  Pubmed ID: 21351773

We report the design and synthesis of an indolyne that displays a reversal in regioselectivity, in both nucleophilic addition and cycloaddition reactions, compared to typical 4,5-indolynes. Our approach utilizes simple computations to predict regioselectivity in reactions of unsymmetrical arynes. With this methodology, novel benzenoid-substituted indoles can be accessed with significant regiocontrol. Furthermore, the technology provides an unconventional tactic for the synthesis of C4-substituted indole alkaloids, as demonstrated by a synthesis of indolactam V.

Paternal Age Related Schizophrenia (PARS): Latent Subgroups Detected by K-means Clustering Analysis

Schizophrenia Research. May, 2011  |  Pubmed ID: 21353765

Paternal age related schizophrenia (PARS) has been proposed as a subgroup of schizophrenia with distinct etiology, pathophysiology and symptoms. This study uses a k-means clustering analysis approach to generate hypotheses about differences between PARS and other cases of schizophrenia.

New Options for the Management of Castration-resistant Prostate Cancer: a Case Perspective

Journal of the National Comprehensive Cancer Network : JNCCN. Feb, 2011  |  Pubmed ID: 21357663

Prostate cancer is the leading cause of cancer and second leading cause of death among men. Management of localized disease is fairly straight-forward, but treatment for locally advanced or metastatic disease is much less so. Androgen-deprivation therapy serves as the foundation of treatment for patients with locally advanced or metastatic disease. Although most patients with prostate cancer show a response to medical or surgical castration, many eventually experience a hormone-refractory, incurable state. Until recently, therapeutic options for CRPC have been limited and focused on systemic chemotherapeutic options. Unfortunately, however, this provides a minimal increase in overall survival, at the cost of significant additional toxicities. Therefore, much research has gone into developing other suitable therapies with potentially less toxicity. This article uses a case study approach to discuss new options for the treatment of castration-resistant prostate cancer.

The Effect of Radiation Quality on Genomic DNA Methylation Profiles in Irradiated Human Cell Lines

Radiation Research. May, 2011  |  Pubmed ID: 21375360

It has been acknowledged for many years that radiation exposure induces delayed, non-targeted effects in the progeny of the irradiated cell. Evidence is beginning to demonstrate that among these delayed effects of radiation are epigenetic aberrations, including altered DNA methylation. To test the hypothesis that differences in radiation quality affect radiation-induced DNA methylation profiles, normal AG01522 and RKO colon carcinoma cells were exposed to low-LET X rays and protons or high-LET iron ions. DNA methylation was then evaluated at delayed times using assays for p16 and MGMT promoter, LINE-1 and alu repeat element, and global methylation. The results of these experiments demonstrated radiation-induced changes in repeat element and global DNA methylation patterns at ∼20 population doublings postirradiation. Further, radiation-induced changes in repeat element and global DNA methylation were more similar between proton- and iron-ion-irradiated cells than X-irradiated cells, suggesting that radiation quality rather than LET alone affects the radiation-induced epigenetic profile. Since alterations in DNA methylation have also emerged as one of the most consistent molecular alterations in cancer, these data also suggest the possibility that radiation-induced carcinogenic risk might be affected by radiation quality.

Persistent Petrosquamosal Sinus: High Incidence in Cases of Complete Aplasia of the Semicircular Canals

Radiology. Jun, 2011  |  Pubmed ID: 21386054

To determine the frequency and to describe the morphologic characteristics and associated skull base anomalies of the petrosquamosal sinus (PSS) in cochlear implant candidates with complete aplasia of the semicircular canals (SCCs).

Highly Potent 5-aminotetrahydropyrazolopyridines: Enantioselective Dopamine D3 Receptor Binding, Functional Selectivity, and Analysis of Receptor-ligand Interactions

Journal of Medicinal Chemistry. Apr, 2011  |  Pubmed ID: 21388142

Heterocyclic dopamine surrogates of types 5 and 7 were synthesized and investigated for their dopaminergic properties. The enantiomerically pure biphenylcarboxamide (S)-5a displayed an outstanding K(i) of 27 pM at the agonist-labeled D(3) receptor and significant selectivity over the D(2) subtype. Measurement of [(35)S]GTPγS incorporation in the presence of a coexpressed PTX-insensitive G(α0-1) subunit indicated highly efficient G-protein coupling. Comparison of ligand efficacy data from cAMP accumulation and [(3)H]thymidine incorporation experiments revealed that ligand biased signaling is exerted by the test compound (S)-5a. Starting from the D(3) crystal structure, a combination of homology modeling and site directed mutagenesis gave valuable insights into the binding mode and the intermolecular origins of stereospecific receptor recognition. According to these data, the superior affinity of the eutomer 5a is caused by the favorable binding energy that results from interaction between the ligand's central ammonium unit and the aspartate residue in position 3.32 of the receptor.

Spontaneous Formation of Novel Luminescent Dinuclear Lanthanide Complexes That Emit in the Visible and Near-IR Regions

Inorganic Chemistry. Apr, 2011  |  Pubmed ID: 21391667

The reaction of tetrasodium-4,4',6,6'-tetracarboxy-2,2'-bipyridine (Na(4)L) with various lanthanide ions yields a family of isostructural supramolecular {Na(2)[Ln(2)L(2)]} complexes (1-4), where Ln(III) = Eu, Nd, Gd, and Tb. Strikingly, these complexes luminesce in buffered H(2)O or D(2)O solutions in either the visible or near-IR regions, despite their high hydration states.

Estrogen Receptor-beta Sensitizes Breast Cancer Cells to the Anti-estrogenic Actions of Endoxifen

Breast Cancer Research : BCR. 2011  |  Pubmed ID: 21392396

We have previously demonstrated that endoxifen is the most important tamoxifen metabolite responsible for eliciting the anti-estrogenic effects of this drug in breast cancer cells expressing estrogen receptor-alpha (ERα). However, the relevance of ERβ in mediating endoxifen action has yet to be explored. Here, we characterize the molecular actions of endoxifen in breast cancer cells expressing ERβ and examine its effectiveness as an anti-estrogenic agent in these cell lines.

Ergot Cluster-encoded Catalase is Required for Synthesis of Chanoclavine-I in Aspergillus Fumigatus

Current Genetics. Jun, 2011  |  Pubmed ID: 21409592

Genes required for ergot alkaloid biosynthesis are clustered in the genomes of several fungi. Several conserved ergot cluster genes have been hypothesized, and in some cases demonstrated, to encode early steps of the pathway shared among fungi that ultimately make different ergot alkaloid end products. The deduced amino acid sequence of one of these conserved genes (easC) indicates a catalase as the product, but a role for a catalase in the ergot alkaloid pathway has not been established. We disrupted easC of Aspergillus fumigatus by homologous recombination with a truncated copy of that gene. The resulting mutant (ΔeasC) failed to produce the ergot alkaloids typically observed in A. fumigatus, including chanoclavine-I, festuclavine, and fumigaclavines B, A, and C. The ΔeasC mutant instead accumulated N-methyl-4-dimethylallyltryptophan (N-Me-DMAT), an intermediate recently shown to accumulate in Claviceps purpurea strains mutated at ccsA (called easE in A. fumigatus) (Lorenz et al. Appl Environ Microbiol 76:1822-1830, 2010). A ΔeasE disruption mutant of A. fumigatus also failed to accumulate chanoclavine-I and downstream ergot alkaloids and, instead, accumulated N-Me-DMAT. Feeding chanoclavine-I to the ΔeasC mutant restored ergot alkaloid production. Complementation of either ΔeasC or ΔeasE mutants with the respective wild-type allele also restored ergot alkaloid production. The easC gene was expressed in Escherichia coli, and the protein product displayed in vitro catalase activity with H(2)O(2) but did not act, in isolation, on N-Me-DMAT as substrate. The data indicate that the products of both easC (catalase) and easE (FAD-dependent oxidoreductase) are required for conversion of N-Me-DMAT to chanoclavine-I.

Complications of HIV Infection in an Ageing Population: Challenges in Managing Older Patients on Long-term Combination Antiretroviral Therapy

The Journal of Antimicrobial Chemotherapy. Jun, 2011  |  Pubmed ID: 21421583

With the use of combination antiretroviral therapy, the proportion of HIV-infected patients over age 50 has greatly increased. The rate of progression of untreated HIV disease, response to therapy and complicating effects of co-morbidities differ in older versus younger patients. Compared with younger individuals, older untreated HIV patients demonstrate faster rates of CD4+ cell loss and more rapid progression to AIDS and death. With treatment, older patients have a better virological response, but a less robust immunological response. The treatment of older HIV-infected patients is further complicated by pre-existing co-morbid conditions including cardiovascular, hepatic and metabolic complications that may be exacerbated by the effects of HIV infection per se, modest immunodeficiency (i.e. at CD4+ counts >350 cells/mm³), and the metabolic and other adverse effects of combination antiretroviral therapy. Based on these considerations guidelines for the treatment of HIV-infected patients state that increased age is a consideration in initiating antiretroviral therapy in persons with >350-500 CD4+ cells/mm³.

Reanalysis of Coreceptor Tropism in HIV-1-infected Adults Using a Phenotypic Assay with Enhanced Sensitivity

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. Apr, 2011  |  Pubmed ID: 21427401

The enhanced-sensitivity Trofile assay (TF-ES; Monogram Biosciences) was used to retest coreceptor tropism samples from 4 different cohorts of HIV-1-infected patients. Nine percent to 26% of patients with CCR5-tropic virus by the original Trofile assay had CXCR4-using virus by TF-ES. Lower CD4 cell counts were associated with CXCR4-using virus in all cohorts.

Respiratory Systolic Variation Test in Acutely Impaired Cardiac Function for Predicting Volume Responsiveness in Pigs

British Journal of Anaesthesia. May, 2011  |  Pubmed ID: 21441547

Predicting the response of cardiac output (CO) to volume administration remains difficult, in particular in patients with acutely compromised cardiac function, where, even small amounts of i.v. fluids can lead to volume overload. We compared the ability to predict volume responsiveness of different functional haemodynamic parameters, such as pulse pressure variation (PPV), stroke volume variation (SVV), the static preload parameter right atrial pressure (RAP), and global end-diastolic volume (GEDV) with the recently proposed respiratory systolic variation test (RSVT) in acutely impaired cardiac function.

Discovery of Kibdelomycin, a Potent New Class of Bacterial Type II Topoisomerase Inhibitor by Chemical-genetic Profiling in Staphylococcus Aureus

Chemistry & Biology. Aug, 2011  |  Pubmed ID: 21867911

Bacterial resistance to known therapeutics has led to an urgent need for new chemical classes of antibacterial agents. To address this we have applied a Staphylococcus aureus fitness test strategy to natural products screening. Here we report the discovery of kibdelomycin, a novel class of antibiotics produced by a new member of the genus Kibdelosporangium. Kibdelomycin exhibits broad-spectrum, gram-positive antibacterial activity and is a potent inhibitor of DNA synthesis. We demonstrate through chemical genetic fitness test profiling and biochemical enzyme assays that kibdelomycin is a structurally new class of bacterial type II topoisomerase inhibitor preferentially inhibiting the ATPase activity of DNA gyrase and topoisomerase IV. Kibdelomycin is thus the first truly novel bacterial type II topoisomerase inhibitor with potent antibacterial activity discovered from natural product sources in more than six decades.

Evaluation of CYP2D6 and Efficacy of Tamoxifen and Raloxifene in Women Treated for Breast Cancer Chemoprevention: Results from the NSABP P1 and P2 Clinical Trials

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. Nov, 2011  |  Pubmed ID: 21880792

Controversy exists regarding the association between CYP2D6 enzyme activity and tamoxifen effectiveness in the adjuvant treatment of invasive breast cancer; however, this association in the primary prevention of breast cancer is unknown.

Evaluating Self-efficacy for Managing Chronic Disease: Psychometric Properties of the Six-item Self-Efficacy Scale in Germany

Journal of Evaluation in Clinical Practice. Aug, 2011  |  Pubmed ID: 21883720

Objective  Self-efficacy - the confidence to carry out certain behaviour in order to achieve a specific goal - has increasingly been recognized as an essential prerequisite of effective self-management of chronic diseases. Therefore, valid and reliable measures are needed to evaluate self-efficacy in both research and clinical practice. This study explored the psychometric properties of the German version of the Self-Efficacy for Managing Chronic Disease 6-Item Scale (SES6G). Methods  We performed standardized translation and cultural adaptation of the SES6G into German. The SES6G was externally validated with the German General Self-Efficacy Scale (SWE). Cronbach's alpha, descriptive statistics and principal component analysis were used to assess psychometric properties of the SES6G. We assessed the effect of the number of co-occurring chronic diseases on SES6G scores using linear regression modelling by controlling for age, gender and education level. Results  We analysed data of 244 primary care patients in Germany. The SES6G showed good convergent construct validity to the SWE (spearman rank correlation 0.578, P < 0.001) and high internal consistency (Cronbach's alpha 0.930). Principal component analysis underlined the one-dimensional structure of the instrument. Adjusted for age and gender, increasing numbers of co-occurring chronic diseases were associated with lower SES6G scores (standardized β-value -0.27, P < 0.001). Education level showed no significant effect. Conclusions  The SES6G is a reliable and valid instrument to assess patients' self-efficacy for managing chronic diseases. It may enhance further research in German-speaking countries and appears to be a valuable measure for clinical practice.

New Imaging Techniques and Opportunities in Endoscopy

Nature Reviews. Gastroenterology & Hepatology. Oct, 2011  |  Pubmed ID: 21894196

Gastrointestinal endoscopy is undergoing major improvements, which are driven by new available technologies and substantial refinements of optical features. In this Review, we summarize available and evolving imaging technologies that could influence the clinical algorithm of endoscopic diagnosis. Detection, characterization and confirmation are essential steps required for proper endoscopic diagnosis. Optical and nonoptical methods can help to improve each step; these improvements are likely to increase the detection rate of neoplasias and reduce unnecessary endoscopic treatments. Furthermore, functional and molecular imaging are emerging as new diagnostic tools that could provide an opportunity for personalized medicine, in which endoscopy will define disease outcome or predict the response to targeted therapy.

BMP Activity Controlled by BMPER Regulates the Proinflammatory Phenotype of Endothelium

Blood. Nov, 2011  |  Pubmed ID: 21900199

The endothelium plays a pivotal role in vascular inflammation. Here we study bone morphogenetic protein (BMP) signaling in endothelial inflammation and in particular the role of BMPER, an extracellular BMP modulator that is important in vascular development and angiogenesis. Using the BMP antagonist dorsomorphin or BMP2 as an agonist we show that BMP signaling is essential for the inflammatory response of vascular endothelial cells as demonstrated by intravital microscopy. We found that BMPER is decreased in inflammation similar to vascular protective genes like KLF2 and eNOS. Using in vitro and in vivo models we show that BMPER is down-regulated through the TNFα-NFκB-KLF2 signaling pathway. Functionally, lack of BMPER induced by siRNA or in BMPER(+/-) mice confers a proinflammatory endothelial phenotype with reduced eNOS levels and enhanced expression of adhesion molecules leading to increased leukocyte adhesion and extravasation in ex vivo and in vivo experiments. Vice versa, addition of BMPER exerts endothelium protective functions and antagonizes TNFα induced inflammation. Mechanistically, we demonstrate that these effects of BMPER are dependent on BMP signaling because of enhanced NFκB activity. In conclusion, the BMP modulator BMPER is a new protective regulator of vascular inflammation that modulates leukocyte adhesion and migration in vitro and in vivo.

Perioperative Fluid and Volume Management: Physiological Basis, Tools and Strategies

Annals of Intensive Care. 2011  |  Pubmed ID: 21906324

ABSTRACT: Fluid and volume therapy is an important cornerstone of treating critically ill patients in the intensive care unit and in the operating room. New findings concerning the vascular barrier, its physiological functions, and its role regarding vascular leakage have lead to a new view of fluid and volume administration. Avoiding hypervolemia, as well as hypovolemia, plays a pivotal role when treating patients both perioperatively and in the intensive care unit. The various studies comparing restrictive vs. liberal fluid and volume management are not directly comparable, do not differ (in most instances) between colloid and crystalloid administration, and mostly do not refer to the vascular barrier's physiologic basis. In addition, very few studies have analyzed the use of advanced hemodynamic monitoring for volume management.This article summarizes the current literature on the relevant physiology of the endothelial surface layer, discusses fluid shifting, reviews available research on fluid management strategies and the commonly used fluids, and identifies suitable variables for hemodynamic monitoring and their goal-directed use.

On-column Solvent Exchange for Purified Preparative Fractions

Journal of Laboratory Automation. Oct, 2011  |  Pubmed ID: 21906559

On-column solvent exchange, using many of the principles of solid-phase extraction, has been implemented to significantly reduce evaporation cycle time following reverse-phase preparative HPLC. Additional benefits, such as a reduced potential for salt formation, thermal decomposition, and residual solvent, are also described. Fractions obtained from preparative separations, typically in a large volume of acetonitrile:water, are injected into the preparative HPLC and then eluted in acetonitrile, creating a new fraction in a volatile organic solvent. Minimal modification to the instrument was required, and unattended operation is possible. Acetonitrile evaporation is achieved within 3 h, compared with 17 h for aqueous-based fractions; lower temperatures can be used during the evaporation step; mobile-phase additives, likely to form salts with the target compound if concentrated in the fraction, are removed before evaporation; sample recovery and purity are unaffected.

Neural Responses to Negative Feedback Are Related to Negative Emotionality in Healthy Adults

Social Cognitive and Affective Neuroscience. Sep, 2011  |  Pubmed ID: 21917847

Prior neuroimaging and electrophysiological evidence suggests that potentiated responses in the anterior cingulate cortex (ACC), particularly the rostral ACC, may contribute to abnormal responses to negative feedback in individuals with elevated negative affect and depressive symptoms. The feedback-related negativity (FRN) represents an electrophysiological index of ACC-related activation in response to performance feedback. The purpose of the present study was to examine the FRN and underlying ACC activation using low resolution electromagnetic tomography source estimation techniques in relation to negative emotionality (a composite index including negative affect and subclinical depressive symptoms). To this end, 29 healthy adults performed a monetary incentive delay task while 128-channel event-related potentials were recorded. We found that enhanced FRNs and increased rostral ACC activation in response to negative-but not positive-feedback was related to greater negative emotionality. These results indicate that individual differences in negative emotionality-a putative risk factor for emotional disorders-modulate ACC-related processes critically implicated in assessing the motivational impact and/or salience of environmental feedback.

When Nursing Takes Ownership of Financial Outcomes: Achieving Exceptional Financial Performance Through Leadership, Strategy, and Execution

Nursing Economic$. Jul-Aug, 2011  |  Pubmed ID: 21919414

With nurses and unlicensed supportive personnel composing the greatest percentage of the workforce at any hospital, it is not surprising nursing leadership plays an increasing role in the attainment of financial goals. The nursing leadership team at one academic medical center reduced costs by more than $10 million over 4 years while outperforming national benchmarks on nurse-sensitive quality indicators. The most critical success factor in attaining exceptional financial performance is a personal and collective accountability to achieving outcomes. Whether it is financial improvement, advancing patient safety, or ensuring a highly engaged workforce, success will not be attained without thoughtful, focused leadership. The accountability model ensures there is a culture built around financial performance where nurses and leaders think and act, on a daily basis, in a manner necessary to understand opportunities, find answers, and overcome obstacles. While structures, processes, and tools may serve as the means to achieve a target, it is leadership's responsibility to set the right goal and motivate others.

Detection of Right Ventricular Insufficiency and Guidance of Volume Therapy Are Facilitated by Simultaneous Monitoring of Static and Functional Preload Parameters

Journal of Cardiothoracic and Vascular Anesthesia. Dec, 2011  |  Pubmed ID: 21924635

Acute right ventricular failure (RVF) is a life-threatening condition. This study investigated whether the combination of central venous pressure (CVP) and left ventricular functional preload parameters, such as stroke volume variation (SVV) and pulse pressure variation (PPV), can be used for the detection of acute RVF and for guidance of volume therapy.

Validating Smoking Data from the Veteran's Affairs Health Factors Dataset, an Electronic Data Source

Nicotine & Tobacco Research : Official Journal of the Society for Research on Nicotine and Tobacco. Dec, 2011  |  Pubmed ID: 21911825

We assessed smoking data from the Veterans Health Administration (VHA) electronic medical record (EMR) Health Factors dataset.

Temporal Stability of the Unified Dyskinesia Rating Scale

Movement Disorders : Official Journal of the Movement Disorder Society. Dec, 2011  |  Pubmed ID: 21915907

The objective of this study was to establish temporal stability characteristics for objective components of the Unified Dyskinesia Rating Scale (UDysRS). The UDysRS has strong internal consistency and a reliable factor structure, but the important issue of temporal stability has not been established.

Breast Medical Oncologists' Use of Standard Prognostic Factors to Predict a 21-gene Recurrence Score

The Oncologist. 2011  |  Pubmed ID: 21934103

Half of all breast cancers are early stage, lymph node negative, and hormone receptor positive. A 21-gene (Oncotype DX®; Genomic Health, Inc., Redwood City, CA) recurrence score (RS) is prognostic for recurrence and predictive of chemotherapy benefit. We explored the ability of oncologists to predict the RS using standard prognostic criteria.

Exportability of an Intervention to Increase HIV Testing in the Veterans Health Administration

Joint Commission Journal on Quality and Patient Safety / Joint Commission Resources. Dec, 2011  |  Pubmed ID: 22235540

Exportability, or the dissemination of successful health services interventions from one site to another, must be demonstrated before systemwide implementation.

Directional Limits on Persistent Gravitational Waves Using LIGO S5 Science Data

Physical Review Letters. Dec, 2011  |  Pubmed ID: 22243300

The gravitational-wave (GW) sky may include nearby pointlike sources as well as stochastic backgrounds. We perform two directional searches for persistent GWs using data from the LIGO S5 science run: one optimized for pointlike sources and one for arbitrary extended sources. Finding no evidence to support the detection of GWs, we present 90% confidence level (C.L.) upper-limit maps of GW strain power with typical values between 2-20×10(-50)  strain(2) Hz(-1) and 5-35×10(-49)  strain(2) Hz(-1) sr(-1) for pointlike and extended sources, respectively. The latter result is the first of its kind. We also set 90% C.L. limits on the narrow-band root-mean-square GW strain from interesting targets including Sco X-1, SN 1987A and the Galactic center as low as ≈7×10(-25) in the most sensitive frequency range near 160 Hz.

Long Lasting Complex Nocturnal Hallucinations During Osmotic Release Oral System (OROS) Methylphenidate Treatment in a 7-year Old Girl

Neuro Endocrinology Letters. 2011  |  Pubmed ID: 22167138

We report a case of a girl with Attention deficit hyperactivity disorder (ADHD) and Oppositional defiant disorder (ODD) who experienced a 3-hour episode of nocturnal complex bizarre visual hallucinations when treated with 18 mg Osmotic Release Oral System (OROS) methylphenidate (MPH). Nocturnal polysomnography performed two weeks later revealed REM sleep reduction (17%) and fragmentation . Two episodes of confusional arousals were recorded. This finding is typical of parasomnia associated with NREM sleep - disorder of arousal. We hypothesize that this preexisting sleep impairment represents a factor of vulnerability to MPH sleep side effects. In our search of literature, we found no report of nocturnal hallucination alone during treatment with stimulants.

The History of Parkinson's Disease: Early Clinical Descriptions and Neurological Therapies

Cold Spring Harbor Perspectives in Medicine. Sep, 2011  |  Pubmed ID: 22229124

Although components of possible Parkinson's disease can be found in very early documents, the first clear medical description was written in 1817 by James Parkinson. In the mid-1800s, Jean-Martin Charcot was particularly influential in refining and expanding this early description and in disseminating information internationally about Parkinson's disease. He separated Parkinson's disease from multiple sclerosis and other disorders characterized by tremor, and he recognized cases that later would likely be classified among the Parkinsonism-plus syndromes. Early treatments of Parkinson's disease were based on empirical observation, and anticholinergic drugs were used as early as the nineteenth century. The discovery of dopaminergic deficits in Parkinson's disease and the synthetic pathway of dopamine led to the first human trials of levodopa. Further historically important anatomical, biochemical, and physiological studies identified additional pharmacological and neurosurgical targets for Parkinson's disease and allow modern clinicians to offer an array of therapies aimed at improving function in this still incurable disease.

Mapping Migratory Bird Prevalence Using Remote Sensing Data Fusion

PloS One. 2012  |  Pubmed ID: 22235254

Improved maps of species distributions are important for effective management of wildlife under increasing anthropogenic pressures. Recent advances in lidar and radar remote sensing have shown considerable potential for mapping forest structure and habitat characteristics across landscapes. However, their relative efficacies and integrated use in habitat mapping remain largely unexplored. We evaluated the use of lidar, radar and multispectral remote sensing data in predicting multi-year bird detections or prevalence for 8 migratory songbird species in the unfragmented temperate deciduous forests of New Hampshire, USA.

Attenuation of Neurovirulence, Biodistribution, and Shedding of a Poliovirus:rhinovirus Chimera After Intrathalamic Inoculation in Macaca Fascicularis

Journal of Virology. Mar, 2012  |  Pubmed ID: 22171271

A dependence of poliovirus on an unorthodox translation initiation mode can be targeted selectively to drive viral protein synthesis and cytotoxicity in malignant cells. Transformed cells are naturally susceptible to poliovirus, due to widespread ectopic upregulation of the poliovirus receptor, Necl-5, in ectodermal/neuroectodermal cancers. Viral tumor cell killing and the host immunologic response it engenders produce potent, lasting antineoplastic effects in animal tumor models. Clinical application of this principle depends on unequivocal demonstration of safety in primate models for paralytic poliomyelitis. We conducted extensive dose-range-finding, toxicity, biodistribution, shedding, and neutralizing antibody studies of the prototype oncolytic poliovirus recombinant, PVS-RIPO, after intrathalamic inoculation in Macaca fascicularis. These studies suggest that intracerebral PVS-RIPO inoculation does not lead to viral propagation in the central nervous system (CNS), does not cause histopathological CNS lesions or neurological symptoms that can be attributed to the virus, is not associated with extraneural virus dissemination or replication and does not induce shedding of virus with stool. Intrathalamic PVS-RIPO inoculation induced neutralizing antibody responses against poliovirus serotype 1 in all animals studied.

Impairment of Pericardial Leaflet Structure from Balloon-expanded Valved Stents

The Journal of Thoracic and Cardiovascular Surgery. Jan, 2012  |  Pubmed ID: 22244562

OBJECTIVE: Malpositioning is one of the major problems in transcatheter aortic valve implantation. To evaluate the influence of mechanical balloon inflation on aortic valve stent positioning, the expansion process and the impact on the valve leaflet's structure were investigated. METHODS: Custom-made stents were laser cut from a 22-mm diameter stainless steel tube and mounted with a glutaraldehyde-treated bovine pericardial valve. The valved stents were crimped onto a standard balloon catheter and expanded by inflation of the balloon with 2 bar for 3 seconds. Expansion was studied using a high-speed camera, and the histology of the pericardial tissue was analyzed. RESULTS: The valved stents were fully expanded within 3 seconds. Balloon inflation was observed to be asymmetric starting proximally. At the beginning of expansion, the valved stents were pulled proximally. During further inflation, the stents slipped distally on the balloon and experienced a total displacement of 13.5 mm. Macroscopic examination showed severe imprinting of the stent struts into the pericardial tissue. Histology revealed disrupted tissue layers and collagen fibers. CONCLUSIONS: Analysis of valved stent expansion showed a displacement of the stent on the catheter during balloon inflation. Therefore, precise placement of the valved stent cannot be accomplished. Histologic analysis of the expanded pericardial tissue revealed disruption of collagen fibers. Disruption of pericardial tissue structures due to balloon expansion may result in early functional valve failure.

The Alternatively Spliced Acid Box Region Plays a Key Role in FGF Receptor Autoinhibition

Structure (London, England : 1993). Jan, 2012  |  Pubmed ID: 22244757

Uncontrolled fibroblast growth factor (FGF) signaling can lead to human malignancies necessitating multiple layers of self-regulatory control mechanisms. Fibroblast growth factor receptor (FGFR) autoinhibition mediated by the alternatively spliced immunoglobulin (Ig) domain 1 (D1) and the acid box (AB)-containing linker between D1 and Ig domain 2 (D2) serves as the first line of defense to minimize inadvertent FGF signaling. In this report, nuclear magnetic resonance and surface plasmon resonance spectroscopy are used to demonstrate that the AB subregion of FGFR electrostatically engages the heparan sulfate (HS)-binding site on the D2 domain in cis to directly suppress HS-binding affinity of FGFR. Furthermore, the cis electrostatic interaction sterically autoinhibits ligand-binding affinity of FGFR because of the close proximity of HS-binding and primary ligand-binding sites on the D2 domain. These data, together with the strong amino acid sequence conservation of the AB subregion among FGFR orthologs, highlight the universal role of the AB subregion in FGFR autoinhibition.

Cementless Acetabular Fixation in Patients 50 Years and Younger at 10 to 18 Years of Follow-Up

The Journal of Arthroplasty. Jan, 2012  |  Pubmed ID: 22266047

The purpose of the study was to evaluate the 10- to 18-year follow-up of cementless acetabular fixation in patients 50 years and younger. We retrospectively reviewed a consecutive group of 118 patients (144 hips) in whom primary total hip arthroplasty had been performed by 2 surgeons using a cementless acetabular component. Two (1.4%) cementless acetabular components were revised because of aseptic loosening. Twenty-four hips (16.7%) were revised for any mechanical failure of the acetabular component mostly related to acetabular liner wear and osteolysis. The average linear wear rate was 0.19 mm per year, which was higher than our previous reports with cemented acetabular fixation. The fiber mesh ingrowth surface of the cementless acetabular component in this study was superior to cemented acetabular components in terms of fixation. However, the high rates of wear and osteolysis have led to poor overall acetabular component construct survivorship.

Beyond Quantitative Decline: Conceptual Shifts in Adolescents' Development of Interest in Mathematics

Developmental Psychology. Jan, 2012  |  Pubmed ID: 22288365

Research has shown that the average values for academic interest decrease during adolescence. Looking beyond such quantitative decline, we explored qualitative change of interest in the domain of mathematics across adolescence. Study 1 was based on a longitudinal data set (annual assessments from Grade 5 to Grade 9; N = 3,193). Latent variable modeling showed that the measurement coefficients of the latent variable of interest (intercepts, structural weights, and error variances) significantly differed across time points, indicating structural changes of the construct. Study 2 was based on interviews with adolescents (Grades 5 and 9, N = 70). Cognitive validation was used to explore differences in subjective concepts of interest across age groups. As expected, there were significant age-related differences, indicating a shift from an affect-laden concept in 5th grade to a more cognitively oriented concept in 9th grade. The findings suggest that developmental research should integrate quantitative and qualitative perspectives of construct change over time and pay more attention to issues of measurement invariance and qualitative changes of constructs over time. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Isolation, Structure Elucidation, and Antibacterial Activity of Methiosetin, a Tetramic Acid from a Tropical Sooty Mold (Capnodium Sp.)

Journal of Natural Products. Mar, 2012  |  Pubmed ID: 22288374

Drug-resistant bacteria continue to make many existing antibiotic classes ineffective. In order to avoid a future epidemic from drug-resistant bacterial infections, new antibiotics with new modes of action are needed. In an antibiotic screening program for new drug leads with new modes of action using antisense Staphylococcus aureus Fitness Test screening, we discovered a new tetramic acid, methiosetin, from a tropical sooty mold, Capnodium sp. The fungus also produced epicorazine A, a known antibiotic. The structure and relative configuration of methiosetin was elucidated by 2D NMR and ESIMS techniques. Methiosetin and epicorazine A showed weak to modest antibacterial activity against S. aureus and Haemophilus influenzae. The isolation, structure elucidation, and antibacterial activity of both compounds are described.

Primary Cementless Acetabular Fixation at a Minimum of Twenty Years of Follow-up: a Concise Update of a Previous Report

The Journal of Bone and Joint Surgery. American Volume. Feb, 2012  |  Pubmed ID: 22298055

The purpose of the present study was to analyze the longer-term results for a previously reported cohort of patients with cementless acetabular fixation and to compare the results with those for historical controls with cement fixation and a comparable follow-up period. One hundred and twenty consecutive nonselected total hip arthroplasties were performed in 108 patients with use of a cementless acetabular component. This series was evaluated at a minimum of twenty years of follow-up and was compared with 330 consecutive hip arthroplasties that had been performed by the same surgeon with use of cemented acetabular components and had been followed for a comparable period of time. Thirty-nine patients (forty-two hips) in the cementless fixation group were living at twenty years of follow-up. In the group of 120 hips with cementless acetabular fixation, twenty-two hips (18.3%) were revised during the follow-up period, but only one hip (0.8%) was revised because of loosening of the acetabular component, with no additional cup loosening since the previous report at thirteen to fifteen years of follow-up. In the group with cemented acetabular fixation with comparable follow-up, thirty-two hips (10%) were revised overall and eighteen hips (6%) were revised because of acetabular loosening. An additional twenty-five hips (8%) had acetabular cups that were loose on radiographs but had not undergone revision. At a minimum of twenty years of follow-up, cementless acetabular components provided superior long-term fixation compared with cemented components but the overall rates of acetabular revision for mechanical reasons were comparable.

N-linked Glycan Structures and Their Expressions Change in the Blood Sera of Ovarian Cancer Patients

Journal of Proteome Research. Apr, 2012  |  Pubmed ID: 22304416

Glycosylated proteins play important roles in a broad spectrum of biochemical and biological processes, and prior reports have suggested that changes in protein glycosylation occur during cancer initiation and progression. Ovarian cancer (OC) is a fatal malignancy, most commonly diagnosed after the development of metastases. Therefore, early detection of OC is key to improving survival. To this end, specific changes of the serum glycome have been proposed as possible biomarkers for different types of cancers. In this study, we extend this concept to OC. To characterize differences in total N-glycan levels, serum samples provided by 20 healthy control women were compared to those acquired from patients diagnosed with late-stage recurrent OC who were enrolled in an experimental treatment trial prior to receiving therapy (N = 19) and one month later, prior to the second treatment cycle (N = 11). Additionally, analyses of the N-glycans associated with IgG and characterization of the relative abundance levels of core vs outer-arm fucosylation were also performed. The N-linked glycomic profiles revealed increased abundances of tri- and tetra-branched structures with varying degrees of sialylation and fucosylation and an apparent decrease in the levels of "bisecting" glycans in OC samples compared to controls. Increased levels of a-galactosylation structures were observed on N-linked glycans derived from IgG, which were independent of the presence of fucose residues. Elevated levels of outer-arm fucosylation were also identified in the OC samples. These results allowed the control samples to be distinguished from the baseline ovarian cancer patients prior to receiving the experimental treatment. In some cases, the pre-treatment samples could be distinguished from the post-experimental treatment samples, as many of those patients showed a further progression of the disease.

Non-curative Gastric Resection for Patients with Stage 4 Gastric Cancer-a Single Center Experience and Current Review of Literature

Langenbeck's Archives of Surgery / Deutsche Gesellschaft Fur Chirurgie. Feb, 2012  |  Pubmed ID: 22307547

PURPOSE: The majority of patients with gastric cancer present with an advanced stage and, therefore, may not be eligible for curative treatment. The role of non-curative gastric resection in situations other than emergency treatment for life threatening tumor-related complications is still under discussion. METHODS: Data from 290 consecutive patients with advanced gastric cancer who were treated in our hospital were analyzed. A total of 48 patients underwent primary non-curative gastric resection. RESULTS: The overall survival in the non-curatively resected group was 15 months and 6 months for non-resected patients, respectively (p < 0.001). The incidence of tumor-related complications which required intervention was 63% in non-resected patients as compared to 12% in patients who underwent primary non-curative resection. Younger age, less than three tumor locations, and chemotherapy have been identified as prognostic factors for improved survival by univariate analysis. D3 lymph node involvement and chemotherapy were independent prognostic factors in the multivariate analysis. Peritoneal carcinosis did not significantly influence survival in resected patients. Non-curative resection in combination with chemotherapy resulted in longer overall survival than resection alone. CONCLUSIONS: Primary non-curative gastric resection can reduce the incidence of severe tumor-related complications and can prolong overall survival in selected subgroups. In particular, younger patients with no more than two tumor locations should be considered for this procedure.

An Efficient Computational Model to Predict the Synthetic Utility of Heterocyclic Arynes

Angewandte Chemie (International Ed. in English). Mar, 2012  |  Pubmed ID: 22307724

Think before you act: a computational approach is reported for evaluating the synthetic potential of heterocyclic arynes. Routine and rapid calculations of arene dehydrogenation energies and aryne angle distortion predict the likelihood that a given hetaryne can be generated, as well as the degree of regioselectivity expected in a reaction between a given hetaryne and a nucleophilic trapping agent.

Current Standards in the Management of Cerebral Metastases

International Journal of Surgical Oncology. 2012  |  Pubmed ID: 22312540

The last 30 years have seen major changes in attitude toward patients with cerebral metastases. This paper aims to outline the major landmarks in this transition and the therapeutic strategies currently used. The controversies surrounding control of brain disease are discussed, and two emerging management trends are reviewed: tumor bed radiosurgery and salvage radiation.

Fibroblast Growth Factor 21 Promotes Bone Loss by Potentiating the Effects of Peroxisome Proliferator-activated Receptor γ

Proceedings of the National Academy of Sciences of the United States of America. Feb, 2012  |  Pubmed ID: 22315431

The endocrine hormone fibroblast growth factor 21 (FGF21) is a powerful modulator of glucose and lipid metabolism and a promising drug for type 2 diabetes. Here we identify FGF21 as a potent regulator of skeletal homeostasis. Both genetic and pharmacologic FGF21 gain of function lead to a striking decrease in bone mass. In contrast, FGF21 loss of function leads to a reciprocal high-bone-mass phenotype. Mechanistically, FGF21 inhibits osteoblastogenesis and stimulates adipogenesis from bone marrow mesenchymal stem cells by potentiating the activity of peroxisome proliferator-activated receptor γ (PPAR-γ). Consequently, FGF21 deletion prevents the deleterious bone loss side effect of the PPAR-γ agonist rosiglitazone. Therefore, FGF21 is a critical rheostat for bone turnover and a key integrator of bone and energy metabolism. These results reveal that skeletal fragility may be an undesirable consequence of chronic FGF21 administration.

Controlling the Position and the Dislocation of the Middle Ear Transducer with High-resolution Computed Tomography and Digital Volume Tomography: Implications for the Transducers' Design

European Archives of Oto-rhino-laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. Apr, 2012  |  Pubmed ID: 21938527

A minimal tip dislocation of the middle ear transducer (MET(®), Otologics Ltd) may result in poor hearing performance. Our objective was to examine if a defined MET dislocation can be diagnosed by high-resolution computed tomography (HRCT) or digital volume tomography (DVT). A human cadaver head was sequentially implanted with different MET tips (incus application) including a ceramic tip (T 1c), a titanium tip (T 1t), a new, thinner titanium tip (T 2), and a spherical titanium tip (Ts). HRCT and DVT studies were performed. Afterward, the tips were pulled back 0.5 mm, so that they were not attached to the incus. HRCT and DVT scans were repeated to identify the dislocation. Using the best plain in HRCT images, the dislocation of the transducer could be measured reliably and reproducibly in half of the cases. In particular, the precise positioning and the dislocation could be identified when T 1t and Ts were implanted, with the Ts showing the best visibility. DVT failed in recognizing the dislocation in all cases. The identification of MET tip's dislocation with HRCT depends on the shape, size, and material of the tip. This knowledge is useful for the design of the implants, as determination of the right position of the middle ear transducer may be proven important for the hearing outcome. In some cases, however, surgical exploration may still be required. Although DVT represents a promising imaging method for the otologists, it can barely help when MET dislocation is suspected.

Validation of the MDS-UPDRS Part I for Nonmotor Symptoms in Parkinson's Disease

Movement Disorders : Official Journal of the Movement Disorder Society. Jan, 2012  |  Pubmed ID: 21915909

The UPDRS has been the main outcome measure in studies of PD. Modifications have been made to improve scale properties and represent the breadth of manifestations of PD, particularly nonmotor symptoms (NMS), resulting in the Movement Disorder Society's revision of the UPDRS (MDS-UPDRS). This study was undertaken to determine the validity of MDS-UPDRS Part I (nonmotor experiences of daily living). The MDS-UPDRS and a number of validated scales for the NMS in PD were used in 94 patients with PD from Hoehn and Yahr stage I to V. We assessed reliability, floor and ceiling effects, and correlations with validated scales for the nonmotor symptoms of PD. MDS-UPDRS Part I showed high internal consistency (Cronbach's alpha: 0.85), small floor and ceiling effects (2% floor and 0% ceiling effect), and good concurrent validity (correlation with the original UPDRS Part I: r = 0.81, P < 0.001). The standardized z-score of the MDS-UPDRS Part I score demonstrated high convergent validity with the composite z-score of nonmotor scales (r = 0.89, P < 0.0001), and the two subscores based on the original factor analysis of Part I also had high correlations with the composite z-scores of corresponding nonmotor scales (depression, anxiety, apathy factor score: r = 0.72, P < 0.0001; other nonmotor features factor score: r = 0.87, P < 0.0001). Our data demonstrate that the MDS-UPDRS Part I total score has a strong relationship with a composite score of validated scales for the nonmotor aspects of PD.

Tetrastarch Sustains Pulmonary Microvascular Perfusion and Gas Exchange During Systemic Inflammation

Critical Care Medicine. Feb, 2012  |  Pubmed ID: 21926574

According to Fick's law of diffusion, gas exchange depends on the size and thickness of the blood perfused alveolocapillary membrane. Impairment of either one is tenuous. No data are available concerning the impact of hydroxyethyl starches and saline on pulmonary microperfusion and gas exchange during systemic inflammation.

[Severe Muscular Dystrophy and Pregnancy: Interdisciplinary Challenge]

Der Anaesthesist. Jan, 2012  |  Pubmed ID: 21909709

The muscular dystrophies are degenerative muscle diseases characterized by progressive muscle weakness. The vast majority of women suffering from muscle diseases develop a deterioration of symptoms during pregnancy. Cardiac and respiratory complications are observed in pregnant women with muscular dystrophy especially in the second and third trimester. The successful perioperative therapy of a 32-year-old pregnant tetraplegic woman with a severe limb-girdle type muscular dystrophy who underwent elective Caesarean section is reported. According to the literature epidural and spinal anesthesia are both possible for perioperative anesthetic management in women with limb-girdle dystrophies. Due to the excellent controllability of intrathecal hyperbaric bupivacaine it was decided to use spinal anesthesia and non-invasive positive pressure ventilation was planned in case of impairment of respiratory function. In summary limb-girdle muscular dysthrophies should be managed on an individual basis and spinal anesthesia can be safely used to avoid intubation.

[Acute Exophthalmos]

Klinische Monatsblätter Für Augenheilkunde. Jan, 2012  |  Pubmed ID: 21442572

Are Immunoglobulin A Anti-gliadin Antibodies Helpful in Diagnosing Coeliac Disease in Children Younger Than 2 Years?

Journal of Pediatric Gastroenterology and Nutrition. Jan, 2012  |  Pubmed ID: 21857243

The usefulness of immumoglobulin (Ig) A antibodies to gliadin (AGA-IgA) in addition to IgA anti-endomysium and tissue transglutaminase antibodies was evaluated in 4122 children younger than 2 years with a suspicion of coeliac disease (CD). Eight percent (312/4122) displayed IgA anti-endomysium and/or IgA anti-tissue transglutaminase, whereas 2.1% (85/4122) displayed only AGA-IgA. Clinical data were obtained for 62 of 85 children with isolated AGA-IgA, and 33 children underwent a duodenal biopsy. Histologically proven CD was established for 5 patients, whereas 57 children were diagnosed to experience other diseases. The systematic detection of AGA-IgA using native gliadin conferred no additional diagnostic benefit for the diagnosis of CD in children younger than 2 years of age, except for rare cases.

RoFo : Fortschritte Auf Dem Gebiete Der Rontgenstrahlen Und Der Nuklearmedizin. Feb, 2012  |  Pubmed ID: 22322444

Olfactory Acuity is Associated with Mood and Function in a Pilot Study of Stable Bipolar Disorder Patients

Bipolar Disorders. Feb, 2012  |  Pubmed ID: 22329478

Hardy C, Rosedale M, Messinger JW, Kleinhaus K, Aujero N, Silva H, Goetz RR, Goetz D, Harkavy-Friedman J, Malaspina D. Olfactory acuity is associated with mood and function in a pilot study of stable bipolar disorder patients. Bipolar Disord 2012: 14: 109-117. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives:  Olfactory dysfunction is described in several neuropsychiatric disorders but there is little research on olfactory processing in bipolar disorder. Methods:  We assessed odor detection threshold (sensitivity) and smell identification test scores, along with symptoms, cognition, and social function in 20 DSM-IV bipolar disorder patients and 44 control subjects. Results:  The patient and control groups had similar demographic measures, intelligence, and mean olfaction scores, but significantly differed in social domains, including adjustment, function, and anxiety. Odor detection sensitivity showed significantly opposite correlations for the depressive and manic mood domains in bipolar disorder (r to z = 2.83, p = 0.005). Depressive symptoms were related to increased sensitivity (the ability to detect odors at a lower concentration) and mania symptoms were related to decreased sensitivity for odor detection. Increased sensitivity for odor detection also predicted significantly better employment (r = -0.642, p = 0.024), whereas less sensitivity was associated with social avoidance (r = 0.702, p = 0.024) and social fear (r = 0.610, p = 0.046). Conclusions:  Diminished odor detection sensitivity predicted mania and social avoidance, whereas more sensitive odor detection predicted more depressive symptoms but better employment functioning in bipolar disorder patients. Odor acuity may be an illness state marker of mood syndromes in bipolar disorder. Alternatively, differences in odor acuity may identify heterogeneous subgroups within the bipolar spectrum. Longitudinal assessments in a large, sex-stratified sample are needed to understand the implications of odor sensitivity in patients with bipolar disorder.

Does an Index Composed of Clinical Data Reflect Effects of Inflammation, Coagulation, and Monocyte Activation on Mortality Among Those Aging with HIV?

Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. Apr, 2012  |  Pubmed ID: 22337823

When added to age, CD4 count and human immunodeficiency virus type 1 (HIV-1) RNA alone (Restricted Index), hemoglobin, FIB-4 Index, hepatitis C virus (HCV), and estimated glomerular filtration rate improve prediction of mortality. Weighted and combined, these 7 routine clinical variables constitute the Veterans Aging Cohort Study (VACS) Index. Because nonroutine biomarkers of inflammation (interleukin 6 [IL-6]), coagulation (D-dimer), and monocyte activation (sCD14) also predict mortality, we test the association of these indices and biomarkers with each other and with mortality.

Role of Cis-12-Oxo-Phytodienoic Acid in Tomato Embryo Development

Plant Physiology. Apr, 2012  |  Pubmed ID: 22337921

Oxylipins including jasmonates are signaling compounds in plant growth, development, and responses to biotic and abiotic stresses. In Arabidopsis (Arabidopsis thaliana) most mutants affected in jasmonic acid (JA) biosynthesis and signaling are male sterile, whereas the JA-insensitive tomato (Solanum lycopersicum) mutant jai1 is female sterile. The diminished seed formation in jai1 together with the ovule-specific accumulation of the JA biosynthesis enzyme allene oxide cyclase (AOC), which correlates with elevated levels of JAs, suggest a role of oxylipins in tomato flower/seed development. Here, we show that 35S::SlAOC-RNAi lines with strongly reduced AOC in ovules exhibited reduced seed set similarly to the jai1 plants. Investigation of embryo development of wild-type tomato plants showed preferential occurrence of AOC promoter activity and AOC protein accumulation in the developing seed coat and the embryo, whereas 12-oxo-phytodienoic acid (OPDA) was the dominant oxylipin occurring nearly exclusively in the seed coat tissues. The OPDA- and JA-deficient mutant spr2 was delayed in embryo development and showed an increased programmed cell death in the developing seed coat and endosperm. In contrast, the mutant acx1a, which accumulates preferentially OPDA and residual amount of JA, developed embryos similar to the wild type, suggesting a role of OPDA in embryo development. Activity of the residual amount of JA in the acx1a mutant is highly improbable since the known reproductive phenotype of the JA-insensitive mutant jai1 could be rescued by wound-induced formation of OPDA. These data suggest a role of OPDA or an OPDA-related compound for proper embryo development possibly by regulating carbohydrate supply and detoxification.

MRI Safety of a Programmable Shunt Assistant at 3 and 7 Tesla*

British Journal of Neurosurgery. Feb, 2012  |  Pubmed ID: 22348282

Objective. Several new shunt technologies have been developed to optimize hydrocephalus treatment within the past few years. Overdrainage, however, still remains an unresolved problem. One new technology which may reduce the frequency of this complication is the use of a programmable shunt assistant (proSA). Inactive in a horizontal position, it impedes CSF flow in a vertical position according to a prescribed pressure level ranging from 0 to 40 cm H(2)O. Methods. We exposed the proSA valve in an ex vivo protocol to MR systems operating at 3 and 7 Tesla to investigate its MRI safety. Results. Following 3 Tesla exposure, no changes in valve settings were noted. Adjustment to any pressure level was possible thereafter. The mean deflection angle was 23 ± 3°. After exposure to 7 Tesla, however, there were unintended pressure changes, and the mechanism for further adjustment of the valves even disintegrated. Conclusion. According to the results of this study, proSA is safe with heteropolar vertical magnet alignment at 3 Tesla. Following 7 Tesla exposure, the valves lost their functional capability.

Examination of Glycan Profiles from IgG-Depleted Human Immunoglobulins Facilitated by Microscale Affinity Chromatography

Analytical Chemistry. Apr, 2012  |  Pubmed ID: 22360417

Among the most important proteins involved in disease and healing processes are the immunoglobulins (Igs). Although many of the Igs have been studied through proteomics, aside from IgG, immunoglobulin carbohydrates have not been extensively characterized in different states of health. It seems valuable to develop techniques that permit an understanding of changes in the structures and abundances of Ig glycans in the context of disease onset and progression. We have devised a strategy for characterization of the glycans for the Ig classes other than IgG (i.e., A, D, E, and M) that contain kappa light chains that requires only a few microliters of biological material. First, we designed a microcolumn containing recombinant Protein L that was immobilized on macroporous silica particles. A similarly designed Protein G microcolumn was utilized to first perform an online depletion of the IgG from the sample, human blood serum, and thereby facilitate enrichment of the other Igs. Even though only 3 μL of serum was used in these analyses, we were able to recover a significantly enriched fraction of non-IgG immunoglobulins. The enrichment properties of the Protein L column were characterized using a highly sensitive label-free quantitative proteomics LC-MS/MS approach, and the glycomic profiles of enriched immunoglobulins were measured by MALDI-TOF MS. As a proof of principle, a comparative study was conducted using blood serum from a small group of lung cancer patients and a group of age-matched cancer-free individuals to demonstrate that the method is suitable for investigation of glycosylation changes in disease. The results were in agreement with a glycomic investigation of whole blood serum from a much larger lung cancer cohort.

Volar/dorsal Compressive Mechanical Behavior of the Transverse Carpal Ligament

Journal of Biomechanics. Apr, 2012  |  Pubmed ID: 22381735

Mechanical insult to the median nerve caused by contact with the digital flexor tendons and/or carpal tunnel boundaries may contribute to the development of carpal tunnel syndrome. Since the transverse carpal ligament (TCL) comprises the volar boundary of the carpal tunnel, its mechanics in part govern the potential insult to the median nerve. Using unconfined compression testing in combination with a finite element-based optimization process, nominal stiffness measurements and first-order Ogden hyperelastic material coefficients (μ and α ) were determined to describe the volar/dorsal compressive behavior of the TCL. Five different locations on the TCL were tested, three of which were deep to the origins of the thenar and hypothenar muscles. The average (± standard deviation) low-strain and high-strain TCL stiffness values in compression sites outside the muscle attachment region were 3.6N/mm (±2.7) and 28.0N/mm (±20.2), respectively. The average stiffness values at compression sites with muscle attachments were notably lower, with low-strain and high-strain stiffness values of 1.2N/mm (±0.5) and 9.7N/mm (±4.8), respectively. The average Ogden coefficients for the muscle attachment region were 51.6kPa (±16.5) for μ and 16.5 (±2.0) for α, while coefficients for the non-muscle attachment region were 117.8kPa (±86.8) for μ and 17.2 (±1.6) for α. These TCL compressive mechanical properties can help inprove computational models, which can be used to provide insight into the mechanisms of median nerve injury leading to the onset of carpal tunnel syndrome symptoms.

Status Epilepticus Associated with the Administration of Long-acting Methylphenidate in a 7-year-old Girl

Journal of Clinical Psychopharmacology. Apr, 2012  |  Pubmed ID: 22388167

Low Dose IR-induced IGF-1-sCLU Expression: a P53-repressed Expression Cascade That Interferes with TGFβ1 Signaling to Confer a Pro-survival Bystander Effect

Oncogene. Mar, 2012  |  Pubmed ID: 22391565

Inadvertent mammalian tissue exposures to low doses of ionizing radiation (IR) after radiation accidents, remediation of radioactive-contaminated areas, space travel or a dirty bomb represent an interesting trauma to an organism. Possible low-dose IR-induced bystander effects could impact our evaluation of human health effects, as cells within tissue are not equally damaged after doses of IR 10 cGy. To understand tissue responses after low IR doses, we generated a reporter system using the human clusterin promoter fused to firefly luciferase (hCLUp-Luc). Secretory clusterin (sCLU), an extracellular molecular chaperone, induced by low doses of cytotoxic agents, clears cell debris. Low-dose IR (2 cGy) exposure induced hCLUp-Luc activity with peak levels at 96 h, consistent with endogenous sCLU levels. As doses increased (1 Gy), sCLU induction amplitudes increased and time-to-peak response decreased. sCLU expression was stimulated by insulin-like growth factor-1, but suppressed by p53. Responses in transgenic hCLUp-Luc reporter mice after low IR doses showed that specific tissues (that is, colon, spleen, mammary, thymus and bone marrow) of female mice induced hCLUp-Luc activity more than male mice after whole body (10 cGy) irradiation. Tissue-specific, non-linear dose- and time-responses of hCLUp-Luc and endogenous sCLU levels were noted. Colon maintained homeostatic balance after 10 cGy. Bone marrow responded with delayed, but prolonged and elevated expression. Intraperitoneal administration of α-transforming growth factor (TGF)β1 (1D11), but not control (13C4) antibodies, immediately following IR exposure abrogated CLU induction responses. Induction in vivo also correlated with Smad signaling by activated TGFβ1 after IR. Mechanistically, media with elevated sCLU levels suppressed signaling, blocked apoptosis and increased survival of TGFβ1-exposed tumor or normal cells. Thus, sCLU is a pro-survival bystander factor that abrogates TGFβ1 signaling and most likely promotes wound healing.Oncogene advance online publication, 5 March 2012; doi:10.1038/onc.2012.64.

Glycomic and Proteomic Profiling of Pancreatic Cyst Fluids Identifies Hyperfucosylated Lactosamines on the N-linked Glycans of Overexpressed Glycoproteins

Molecular & Cellular Proteomics : MCP. Mar, 2012  |  Pubmed ID: 22393262

Pancreatic cancer is now the fourth leading cause of cancer deaths in the United States, and it is associated with an alarmingly low 5-year survival rate of 5%. However, the prognosis for a patient is considerably improved when the malignant lesions are identified at an early stage of the disease and removed by surgical resection. Unfortunately, the absence of a practical screening strategy and clinical diagnostic test for identifying pre-malignant lesions within the pancreas often prevents early detection of pancreatic cancer. To aid in the development of a molecular screening system for early detection of the disease, we have performed glycomic and glycoproteomic profiling experiments on 21 pancreatic cyst fluid samples, including fluids from mucinous cystic neoplasms (MCN) and intraductal papillary mucinous neoplasms (IPMN), two types of mucinous cysts, which are considered high-risk to undergo malignant transformation. A total of 80 asparagine-linked (N-linked) glycans, including high-mannose and complex structures, were identified. Of special interest was a series of complex N-linked glycans containing two to six fucose residues, located predominantly as substituents on β-lactosamine extensions. Following the observation of these hyperfucosylated glycans, bottom-up proteomics experiments utilizing a label-free quantitative approach were applied to the investigation of two sets of tryptically-digested proteins derived from the cyst fluids: 1) all soluble proteins in the raw samples and 2) a subproteome of the soluble cyst fluid proteins that were selectively enriched for fucosylation through the use of surface-immobilized Aleuria aurantia lectin (AAL). A comparative analysis of these two proteomic data sets identified glycoproteins that were significantly enriched by lectin affinity. Several candidate glycoproteins that appear hyperfucosylated were identified, including triacylglycerol lipase and pancreatic α-amylase, which were 20- and 22-fold more abundant, respectively, following AAL enrichment.

Use of 3D Properties to Characterize Beyond Rule-of-5 Property Space for Passive Permeation

Journal of Chemical Information and Modeling. Mar, 2012  |  Pubmed ID: 22394163

The application of conformationally dependent measures of size and polarity to characterize beyond rule-of-5 (Ro5) space for passive permeation was investigated. Specifically, radius of gyration, an alternative to molecular weight, and three-dimensional polar surface area and the generalized Born/surface area dehydration free energy, alternatives to hydrogen-bond donor and acceptor counts, were computed on models of the permeating conformations of over 35 000 molecules. The resulting guidelines for size and polarity, described by the 3D properties, should aid the design of Ro5 violators with passive permeability.

Fluid Flows and Forces in Development: Functions, Features and Biophysical Principles

Development (Cambridge, England). Apr, 2012  |  Pubmed ID: 22395739

Throughout morphogenesis, cells experience intracellular tensile and contractile forces on microscopic scales. Cells also experience extracellular forces, such as static forces mediated by the extracellular matrix and forces resulting from microscopic fluid flow. Although the biological ramifications of static forces have received much attention, little is known about the roles of fluid flows and forces during embryogenesis. Here, we focus on the microfluidic forces generated by cilia-driven fluid flow and heart-driven hemodynamics, as well as on the signaling pathways involved in flow sensing. We discuss recent studies that describe the functions and the biomechanical features of these fluid flows. These insights suggest that biological flow determines many aspects of cell behavior and identity through a specific set of physical stimuli and signaling pathways.

Double Trouble: How Big a Problem is Redundant Anaerobic Antibiotic Coverage in Veterans Affairs Medical Centres?

The Journal of Antimicrobial Chemotherapy. Mar, 2012  |  Pubmed ID: 22398652

OBJECTIVES: To assess the prevalence of, and the variation in, avoidable use of metronidazole in the Veterans Affairs (VA) healthcare system METHODS: Barcode Medication Administration (BCMA) data were retrospectively assessed for all patients hospitalized between January 2006 and December 2010 in acute-care wards of all VA medical centres (VAMCs) with complete BCMA data and at least 10 acute-care non-intensive care unit (ICU) beds. Potentially avoidable metronidazole days of therapy (DOT) were defined as the administration of metronidazole with another anti-anaerobic antibiotic on the same day for at least two consecutive days during the same hospitalization. Metronidazole was not considered redundant in combination with another anti-anaerobic agent within 28 days after a positive test for Clostridium difficile and during hospitalizations associated with discharge diagnosis codes for cholecystitis or cholangitis. RESULTS: A total of 128 VAMCs satisfied the inclusion criteria. Over the study period there were a total of 782 821 DOT of metronidazole (57.4 DOT per 1000 patient-days), of which 183 267 (23.4%) fulfilled the criteria for avoidable metronidazole DOT. The percentage of avoidable metronidazole DOT remained stable over the study period (22.8% in 2006 and 22.9% in 2010) despite a decrease in overall metronidazole use. There was wide variation in the percentage of avoidable metronidazole DOT among facilities (2010: median 20.3%, IQR 15.3%-29.4%). Piperacillin/tazobactam was the most commonly administered drug on avoidable metronidazole DOT (56.8%). CONCLUSIONS: Potentially avoidable use of metronidazole affected about a quarter of all days when metronidazole was given. The combination of metronidazole with piperacillin/tazobactam was particularly common and represents a possible target for antibiotic stewardship interventions.

Silencing of HSulf-2 Expression in MCF10DICS.com Cells Attenuate Ductal Carcinoma in Situ Progression to Invasive Ductal Carcinoma in Vivo

Breast Cancer Research : BCR. Mar, 2012  |  Pubmed ID: 22410125

ABSTRACT: INTRODUCTION: Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous group of proliferative cellular lesions that have the potential to become invasive. Very little is known about the molecular alterations involved in the progression from DCIS to invasive ductal carcinoma (IDC). Heparan endosulfatase (HSulf-2) edits sulfate moieties on heparan sulfate proteoglycans (HSPGs) and have been implicated in modulating heparin binding growth factor signaling, angiogenesis and tumorigenesis. However, the role of HSulf-2 in breast cancer progression is poorly understood. MCF10DCIS.com cells (referred as MCF10DCIS) express HSulf-2 and form comedo type DCIS and progress to IDC when transplanted in immune-deficient mice and therefore is an ideal model to study breast cancer progression. We evaluated the role of HSulf-2 in progression from DCIS to IDC using mouse fat pad mammary xenografts. METHODS: Non-target control (NTC) and HSulf-2 knockdown in MCF10DCIS breast cancer cells was achieved by NTC shRNA and two different lentiviral shRNA against HSulf-2 respectively. Xenografts were established by injecting NTC and HSulf-2 deficient MCF10DCIS cells in mouse mammary fat pads. Xenografts were subjected to H&E staining for morphological analysis, TUNEL and Propidium iodide staining to determine extent of apoptosis, Western blot analysis and zymography. RESULTS: Using a mouse mammary fat pad derived xenograft model, we observed that compared to control treated xenografts, downregulation of HSulf-2 was associated with significant delays in growth at week 7 (p value<0.05). Histological examination of the tumors demonstrated substantial differences in comedo necrosis, with marked luminal apoptosis and upregulation of apoptotic markers Bim, cleaved PARP and cleaved caspase 3 in the control treated versus the HSulf-2 depleted xenografts. Furthermore, HSulf-2 depleted xenografts retained the basement membrane integrity with decreased activity and expression of matrix metalloproteinase 9 (MMP-9), an enzyme critical for degradation of extracellular matrix compared to nontargeted control. CONCLUSION: Our data suggest that HSulf-2 expression may be critical for human breast cancer progression. Downregulation of HSulf-2 leads to retention of comedo type DCIS and delays the progression of DCIS to IDC. Further studies are necessary to determine if therapeutic targeting of HSulf-2 expression might delay the progression of DCIS to IDC.

Entorhinal Cortex Atrophy Differentiates Parkinson's Disease Patients with and Without Dementia

Movement Disorders : Official Journal of the Movement Disorder Society. Mar, 2012  |  Pubmed ID: 22410753

Volumetric measures of mesial temporal lobe structures on MRI scans recently have been explored as potential biomarkers of dementia in patients with PD, with investigations primarily focused on hippocampal volume. Both in vivo MRI and postmortem tissue studies in Alzheimer's disease, however, demonstrate that the entorhinal cortex (ERC) is involved earlier in disease-related pathology than the hippocampus. The ERC, a region integral in declarative memory function, projects multimodal sensory information to the hippocampus through the perforant path. In PD, ERC atrophy, as measured on MRI, however, has received less attention, compared to hippocampal atrophy. We compared ERC and hippocampal atrophy in 12 subjects with PD dementia including memory impairment, 14 PD subjects with normal cognition, and 14 healthy controls with normal cognition using manual segmentation methods on MRI scans. Though hippocampal volumes were similar in the two PD cognitive groups, ERC volumes were substantially smaller in the demented PD subjects, compared to cognitively normal PD subjects (P < 0.05). In addition, normalized ERC and hippocampal volumes for right and left hemispheres were significantly lower in the demented PD group, compared to healthy controls. Our findings suggest that ERC atrophy differentiates demented and cognitively normal PD subjects, in contrast to hippocampal atrophy. Thus, ERC atrophy on MRI may be a potential biomarker for dementia in PD, particularly in the setting of memory impairment. © 2012 Movement Disorder Society.

Schizophrenia Comorbid with Panic Disorder: Evidence for Distinct Cognitive Profiles

Psychiatry Research. Mar, 2012  |  Pubmed ID: 22417926

Patients with comorbid schizophrenia and panic symptoms share a distinct clinical presentation and biological characteristics, prompting some to propose panic psychosis as a separate subtype of schizophrenia. Less is known about these patients' neuropsychological profiles, knowledge of which may facilitate target-specific treatments and research into the etiopathophysiology for such cases. A total of 255 schizophrenia patients with panic disorder (n=39), non-panic anxiety disorder (n=51), or no anxiety disorder (n=165) were assessed with the Wechsler Adult Intelligence Scale-Revised, the Wisconsin Card Sorting Test, the Trail Making Test, the Controlled Oral Word Association Test, the Animal Naming subtest of the Boston Diagnostic Aphasia Examination, and the Wechsler Memory Scale-Revised. Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale. Patients with panic disorder demonstrated a higher verbal IQ and better problem solving, set switching, delayed recall, attention, and verbal fluency as compared to schizophrenia patients without comorbid anxiety. The schizophrenia-panic group reported a higher level of dysthymia on stable medication. Our findings suggest that patients with schizophrenia and comorbid panic disorder exhibit distinct cognitive functioning when compared to other schizophrenia patients. These data offer further support for a definable panic-psychosis subtype and suggest new etiological pathways for future research.

The Effect of Automated Telephone Appointment Reminders on HIV Primary Care No-Shows By Veterans

The Journal of the Association of Nurses in AIDS Care : JANAC. Mar, 2012  |  Pubmed ID: 22424961

Appointment attendance for follow-up care and laboratory monitoring are central components of HIV treatment. In general, appointment reminders are an effective method of reducing outpatient no-shows; however, no single strategy has proven superior. This study tested the effectiveness of adding an automated telephone reminder for laboratory monitoring to the standard set of three appointment reminders to reduce subsequent HIV primary care no-shows. We conducted a quasi-experimental design study in three geographically and administratively affiliated Veterans Administration HIV clinics with one clinic serving as the intervention facility and two others as control facilities. The intervention lasted 6 months. The data show that patients who were not homeless, who were not diagnosed with depression, and who had five or more appointments scheduled in 6 months had significantly fewer no-shows after intervention. The intervention was not effective in reducing no-shows among homeless patients, racial/ethnic minorities, and patients with mental health disorders.

[In Process Citation]

RöFo : Fortschritte Auf Dem Gebiete Der Röntgenstrahlen Und Der Nuklearmedizin. Apr, 2012  |  Pubmed ID: 22426868

[Undergraduate Teaching of Anaesthesiology : A Nationwide Survey in Germany]

Der Anaesthesist. Mar, 2012  |  Pubmed ID: 22430550

In 2003 anaesthesiology was implemented as a compulsory speciality of undergraduate teaching in Germany due to the revised regulations of medical education. Besides the preexisting subject of emergency medicine an obligatory course in anaesthesiology was introduced. Thus anaesthesiology has gained considerable importance in all medical faculties. To gain insight into the current status of undergraduate medical education in the university departments of anaesthesiology a nationwide survey at all university departments in Germany was initiated.

Adaptation and Psychometric Properties of the PACIC Short Form

The American Journal of Managed Care. Feb, 2012  |  Pubmed ID: 22435885

Objectives: The Patient Assessment of Chronic Illness Care (PACIC) is a widely used instrument to evaluate the quality and patient-centeredness of chronic illness care based on the Chronic Care Model (CCM). It is a validated and reliable instrument which consists of 20 items. Additionally, a short form with 11 items was developed. The aim of this study was to translate this short form into German and examine the psychometric properties among patients with a chronic illness in Germany. Study Design: Observational study design. Methods: We performed a translation and cultural adaptation of the PACIC short form into German. The German version was externally validated with the 20-item PACIC. Cronbach a, descriptive statistics, and principal component analysis were used to assess psychometric properties. Results: In total, 264 primary care patients completed the PACIC short form. The PACIC short form showed good convergent construct validity to the 20-item PACIC (Spearman rank correlation 0.82, P $lt;.001) and high internal consistency (Cronbach a 0.87). Principal component analysis underlined the 1-dimensional structure of the instrument. No correlation between the mean overall score of the PACIC short form and the number of chronic conditions (r = 0.068; P = .273) was found. Conclusions: The PACIC short form showed good to very good psychometric properties and reliable measures regarding patient assessment of receiving care congruent with the CCM. It is a less burdensome instrument which can be used for further research of patients with more than 1 chronic condition.

MedJet - a New CO2-based Disposable Cleaning Device Allows Safe and Effective Bowel Cleansing During Colonoscopy: a Pilot Study

Endoscopy. Mar, 2012  |  Pubmed ID: 22438188

Background and study aims: Complete bowel cleansing is mandatory for effective colon cancer screening and surveillance. The aim of the current pilot study, which was conducted in humans, was to test the safety and efficiency of a newly developed disposable cleaning device, the MedJet, for intraprocedural bowel cleansing. Patients and methods: Patients with screening or surveillance colonoscopy after previous polypectomy were included. The colonoscope was first inserted to the cecum and the overall cleansing was assessed according to the Ottawa scale. The MedJet device was used if colon cleansing had been incomplete. The MedJet catheter was passed over the working channel of the colonoscope and the colon was cleaned during withdrawal. The MedJet device delivered controlled jets comprising compressed CO2 and minimal amounts of sterile water, which allowed disintegration and removal of residual stool. The efficiency of cleaning was assessed according to the Boston scale. Results: A total of 32 patients (16 female; mean age 61 years) were treated with the device. No device-related adverse or serious adverse events were noted. MedJet application during withdrawal provided effective and significant improvement in bowel cleansing (P = 0.005). Furthermore, 18 adenomas and 1 colon cancer, which were hidden behind stool remnants, could be identified in 11 patients following use of the MedJet device. However, the withdrawal times were prolonged (11.4±6.0 minutes) due to the additional cleaning procedure. All patients tolerated the procedure well. Conclusions: The new MedJet device enabled highly effective and safe bowel cleansing during colonoscopy. The catheter-based system was easy to use and CO2 was applied for cleansing. The procedure was well tolerated by patients.

Effects of One-lung Ventilation on Thermodilution-derived Assessment of Cardiac Output

British Journal of Anaesthesia. Mar, 2012  |  Pubmed ID: 22440313

BACKGROUND: /st>Cardiac output (CO) monitoring can be useful in high-risk patients during one-lung ventilation (OLV), but it is unclear whether thermodilution-derived CO monitoring is valid during OLV. Therefore, we compared pulmonary artery (CO(PATD)) and transcardiopulmonary thermodilution (CO(TPTD)) with an experimental reference in a porcine model. METHODS: /st>CO(PATD) and CO(TPTD) were measured in 23 pigs during double-lung ventilation (DLV) and 15 min after the onset of OLV, during conditions of normovolaemia and after haemorrhage. An ultrasonic flow probe placed around the pulmonary artery (CO(PAFP)) was used for reference. RESULTS: /st>The range of CO in these experiments was 1.5-3 litre min(-1). Normovolaemia: during DLV and conditions of normovolaemia, the mean (95% limits of agreement) bias for CO(PATD) compared with CO(PAFP) was -0.05 (-0.92 and 0.83) litre min(-1), and 0.58 (-0.40 and 1.55) litre min(-1) for CO(TPTD). During OLV, the bias for CO(PATD) remained unchanged at 0.08 (-0.51 and 0.66) litre min(-1), P=0.15, and the bias for CO(TPTD) increased significantly to 0.85 (0.05 and 1.64) litre min(-1), P=0.047. Hypovolaemia: during DLV, the bias for CO(PATD) compared with CO(PAFP) was 0.22 (-0.20 and 0.66) litre min(-1) and for CO(TPTD) was 0.60 (0.12 and 1.10) litre min(-1). There was no significant change of bias during OLV for CO(PATD) [0.30 (-0.10 and 0.70) (litre min(-1)), P=0.25] or bias CO(TPTD) [0.72 (0.21 and 1.22) (litre min(-1)), P=0.14]. Trending ability during OLV, quantified by the mean of angles θ, showed good values for both CO(PATD) (θ=11.2°) and CO(TPTD) (θ=1.3°). CONCLUSIONS: /st>CO(TPTD) is, to some extent, affected by OLV, whereas CO(PATD) is unchanged. Nonetheless, both methods provide an acceptable estimation of CO and particularly of relative changes of CO during OLV.

A Change in Culture: Violence Prevention in an Acute Behavioral Health Setting

Journal of the American Psychiatric Nurses Association. Mar, 2012  |  Pubmed ID: 22442017

A multilayered implementation of safety measures in an inpatient psychiatric facility created a sustained change in culture related to patient and staff safety. The model was developed over a 5-year period in a freestanding 80-bed behavioral health facility that is part of a Level II trauma center in the Midwest. The model has nine components that the nursing leadership team saw as integral to maintaining a safe environment. The nine elements include trauma-informed care principles, aggression management, code event review, leadership involvement, quality feedback, recovery orientation, patient assessment, education, and collaboration. The metrics collected to determine the effectiveness of the model included patient violence events and staff injuries. This article describes the development of this model and its impact on the reduction of patient violence events and staff injuries at this facility. The recommendations include considerations for the replication of this model at other facilities.

Klotho Co-Receptors Inhibit Signaling by Paracrine FGF8 Subfamily Ligands

Molecular and Cellular Biology. Mar, 2012  |  Pubmed ID: 22451487

It has been recently established that Klotho co-receptors associate with fibroblast growth factor receptor tyrosine kinases (FGFRs) to enable signaling by endocrine-acting FGFs. However, the molecular interactions leading to FGF-FGFR-Klotho ternary complex formation remain incompletely understood. Here we show that in contrast to αKlotho, βKlotho binds its cognate endocrine FGF ligand (FGF19 or FGF21) and FGFR independently through two distinct binding sites. FGF19 and FGF21 use their respective C-terminal tails to bind to a common binding site on βKlotho. Importantly, we also show that Klotho co-receptors engage a conserved hydrophobic groove in the immunoglobulin-like domain III (D3) of the "c" splice isoform of FGFR. Intriguingly, this hydrophobic groove is also used by ligands of the paracrine-acting FGF8 subfamily for receptor binding. Based on this binding site overlap, we conclude that while Klotho co-receptors enhance binding affinity of FGFR for endocrine FGFs, they actively suppress binding of FGF8 subfamily ligands to FGFR.

Theoretical Investigation of Biomass Productivities Achievable in Solar Rectangular Photobioreactors for the Cyanobacterium Arthrospira Platensis

Biotechnology Progress. Mar, 2012  |  Pubmed ID: 22467177

Modeling was done to simulate whole-year running of solar rectangular photobioreactors (PBRs). Introducing the concept of ideal reactor, the maximal biomass productivity that could be achieved on Earth on nitrate as N-source was calculated. Two additional factors were also analyzed with respect to dynamic calculations over the whole year: the effect of PBR location and the effects of given operating conditions on the resulting decrease in productivity compared with the ideal one. Simulations were conducted for the cyanobacterium Arthorspira platensis, giving an ideal productivity (upper limit) in the range 55-60 t(x) ha(-1) year(-1) for a sun tracking system (and around 35-40 t(x) ha(-1) year(-1) for a fixed horizontal PBR). For an implantation in France (Nantes, west coast), the modification in irradiation conditions resulted in a decrease in biomass productivity of 40%. Various parameters were investigated, with special emphasis on the influence of the incident angle of solar illumination on resulting productivities, affecting both light capture and light transfer inside the bulk culture. It was also found that with appropriate optimization of the residence time as permitted by the model, productivities close to maximal could be achieved for a given location. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012.

[With the Scalpel Against the Immune System: HIV Infection Complicated by An Unclear Colitis]

Zeitschrift Für Gastroenterologie. Apr, 2012  |  Pubmed ID: 22467540

A 35-year-old Kenian lady with advanced immunodeficiency due to HIV infection started on an antiretroviral therapy. Five months later, a severe colitis was diagnosed, however, no causal pathogen could be found. In order to avoid imminent perforation, a hemicolectomy became necessary, and immediately the symptoms and inflammation markers normalized rapidly. M. tuberculosis could be proven in culture in a draining abdominal lymph node. We assume that the severe inflammation was caused by an immune restoration inflammatory syndrome (IRIS). Essentials in diagnosis, pathogenesis and therapy of IRIS are discussed.

The Growth of Reading Skills in Children with Down Syndrome

Developmental Science. May, 2012  |  Pubmed ID: 22490173

There appears to be a close and probably causal relationship between early variations in phoneme skills and later reading skills in typically developing children, though the pattern in children with Down Syndrome is less clear. We present the results of a 2-year longitudinal study of 49 children with Down Syndrome (DS) and 61 typically developing (TD) control children with similar initial levels of reading skill. Phoneme awareness and vocabulary were strong concurrent predictors of initial levels of reading skill in both groups. However, longitudinally phoneme awareness was a predictor of the growth of reading skills in TD children but not in children with DS. There was a very high degree of longitudinal stability in reading skills in children with DS, and initial levels of reading skills seemed to be highly constrained by general language skills, as indexed by vocabulary knowledge, in this population. We conclude that reading development in children with DS shows similarities and differences to the pattern observed in TD children and that phoneme awareness appears to be a less powerful influence on the development of reading skills in children with DS.

Pulse Oximetry Screening in Wisconsin

Congenital Heart Disease. Apr, 2012  |  Pubmed ID: 22494499

Introduction.  Pulse oximetry can be used as a screening tool to detect critical congenital heart disease (CCHD) in neonates prior to hospital discharge and the development of symptoms. Newborns suspected of having CCHD based on pulse oximetry screening should have the diagnosis excluded or confirmed with echocardiography. However, echocardiography is not immediately available in all settings in which newborns are delivered and the best course of action in these settings remains to be determined. The purpose of this study was to evaluate the resources available to diagnose and treat newborns with CCHD born in the state of Wisconsin. Methods.  We surveyed the nurse managers or administrators of the 99 Wisconsin hospitals in which babies are routinely delivered in the state of Wisconsin. A telephone survey was performed in February and March 2011. The number of births per facility was estimated from the most recent available data (2010). Results.  There were 66 179 total births occurring in 106 hospitals in the state of Wisconsin in 2010, with 99 hospitals routinely delivering newborns. Surveys were completed in 88/99 (88.9%), representing 95% of the state's in-hospital births. All responding hospitals had pulse oximetry available in the nursery. Twenty-five of 88 (28.4%) of responding hospitals routinely use pulse oximetry to screen for CCHD, representing 35.2% of surveyed hospital births. Same-day neonatal echocardiography was available at 33/88 (37.5%) of the responding hospitals, representing 74.4% of surveyed hospital births. The average distance to the higher-level care facility of choice from the hospitals without neonatal echocardiography is 53.1 miles. Conclusion.  Pulse oximetry is universally available in Wisconsin newborn nurseries, and pulse oximetry screening for CCHD is currently being performed for many of Wisconsin's newborns. The majority of births in Wisconsin occur in hospitals where same-day neonatal echocardiography is available for confirmatory diagnosis of CCHD when necessary.

Systematic Intraoperative Application of Confocal Endomicroscopy for Early Detection and Resection of Squamous Cell Carcinoma of the Head and Neck: a Preliminary Report

Archives of Otolaryngology--head & Neck Surgery. Apr, 2012  |  Pubmed ID: 22508625

To use intraoperative confocal endomicroscopy for early detection and resection of squamous cell carcinoma (SCC) of the head and neck. A preliminary report.

Comprehensive Review of Factors Implicated in the Heterogeneity of Response in Depression

Depression and Anxiety. Apr, 2012  |  Pubmed ID: 22511365

Heterogeneity in overall response and outcomes to pharmacological treatment has been reported in several depression studies but with few sources that integrate these results. The goal of this study was to review the literature and attempt to identify nongenetic factors potentially predictive of overall response to depression treatments.

Decay in Blood Loss Estimation Skills After Web-based Didactic Training

Simulation in Healthcare : Journal of the Society for Simulation in Healthcare. Feb, 2012  |  Pubmed ID: 22228284

Accuracy in blood loss estimation has been shown to improve immediately after didactic training. The objective of this study was to evaluate retention of blood loss estimation skills 9 months after a didactic web-based training.

Olfactory Processing, Sex Effects and Heterogeneity in Schizophrenia

Schizophrenia Research. Mar, 2012  |  Pubmed ID: 22177347

Smell identification deficits are associated with negative symptoms in schizophrenia, particularly in males. Far less information is known about the relationship of odor detection sensitivity (acuity) and negative symptoms in schizophrenia, and currently there is a dearth in sex-stratified research specifically examining odor sensitivity and smell identification.

An Exclusive α/β Code Directs Allostery in TetR-peptide Complexes

Journal of Molecular Biology. Feb, 2012  |  Pubmed ID: 22178479

The allosteric mechanism of one of the best characterized bacterial transcription regulators, tetracycline repressor (TetR), has recently been questioned. Tetracycline binding induces cooperative folding of TetR, as suggested by recent unfolding studies, rather than switching between two defined conformational states, namely a DNA-binding-competent conformation and a non-DNA-binding conformation. Upon ligand binding, a host of near-native multiconformational structures collapse into a single, highly stabilized protein conformation that is no longer able to bind DNA. Here, structure-function studies performed with four synthetic peptides that bind to TetR and mimic the function of low-molecular-weight effectors, such as tetracyclines, provide new means to discriminate between different allosteric models. Whereas two inducing peptides bind in an extended β-like conformation, two anti-inducing peptides form an α-helix in the effector binding site of TetR. This exclusive bimodal interaction mode coincides with two distinct overall conformations of TetR, namely one that is identical with induced TetR and one that mirrors the DNA-bound state of TetR. Urea-induced unfolding studies show no increase in thermodynamic stability for any of the peptide complexes, although fluorescence measurements demonstrate peptide binding to TetR. This strongly suggests that, at least for these peptide effectors, a classical two-state allosteric model best describes TetR function.

Monitoring Metabolic Side Effects when Initiating Treatment with Second-generation Antipsychotic Medication

Clinical Schizophrenia & Related Psychoses. Jan, 2012  |  Pubmed ID: 22182457

Published guidelines recommend metabolic monitoring for patients prescribed second-generation antipsychotic (SGA) medications. This study determined monitoring rates, and examined predictors of monitoring, for total cholesterol and weight among patients prescribed SGAs during a period when awareness of metabolic side effects was emerging, but prior to the wide promulgation of guidelines.

A Reverse Binding Motif That Contributes to Specific Protease Inhibition by Antibodies

Journal of Molecular Biology. Jan, 2012  |  Pubmed ID: 22154938

The type II transmembrane serine protease family consists of 18 closely related serine proteases that are implicated in multiple functions. To identify selective, inhibitory antibodies against one particular type II transmembrane serine protease, matriptase [MT-SP1 (membrane-type serine protease 1)], a phage display library was created with a natural repertoire of Fabs [fragment antigen binding (Fab)] from human naïve B cells. Fab A11 was identified with a 720 pM inhibition constant and high specificity for matriptase over other trypsin-fold serine proteases. A Trichoderma reesei system expressed A11 with a yield of ∼200 mg/L. The crystal structure of A11 in complex with matriptase has been determined and compared to the crystal structure of another antibody inhibitor (S4) in complex with matriptase. Previously discovered from a synthetic single-chain variable fragment library, S4 is also a highly selective and potent matriptase inhibitor. The crystal structures of the A11/matriptase and S4/matriptase complexes were solved to 2.1 Å and 1.5 Å, respectively. Although these antibodies, discovered from separate libraries, interact differently with the protease surface loops for their specificity, the structures reveal a similar novel mechanism of protease inhibition. Through the insertion of the H3 variable loop in a reverse orientation at the substrate-binding pocket, these antibodies bury a large surface area for potent inhibition and avoid proteolytic inactivation. This discovery highlights the critical role that the antibody scaffold plays in positioning loops to bind and inhibit protease function in a highly selective manner. Additionally, Fab A11 is a fully human antibody that specifically inhibits matriptase over other closely related proteases, suggesting that this approach could be useful for clinical applications.

A Non-human Primate Model of Bipedal Locomotion Under Restrained Condition Allowing Gait Studies and Single Unit Brain Recordings

Journal of Neuroscience Methods. Mar, 2012  |  Pubmed ID: 22155386

For decades, several animal models of locomotion have allowed a better understanding of the basic physiological mechanisms of gait. However, unlike most of the mammals, the Order Primates is characterized by fundamental changes in locomotor behaviour. In particular, some primates use a specific pattern of locomotion and are able to naturally walk bipedally due possibly to a specific supra-spinal control of locomotion. These features must be taken into account when one considers to study the intrinsic properties of human gait. Thus, an experimental model of bipedal locomotion allowing precise and reproducible analysis of gait in non-human primate is still lacking. This study describes a non-human primate model of bipedal locomotion under restrained condition. We undertook a kinematic and biomechanic study in three Macaca fascicularis trained to walk bipedally on a treadmill. One of the primate was evaluated in complete head fixation. Gait visual analysis and electromyographic recordings provided pertinent description of the gait pattern. Step frequencies, step lengths, cycle and stance phase durations were correlated with Froude number (dimensionless velocity), whereas swing phase durations remained non-correlated. Gait patterns observed in our model were similar to those obtained in freely bipedal Macaca fuscata and to a lesser extend to Humans. Gait pattern was not modified by head fixation thereby allowing us to perform precise and repetitive micro electrode recordings of deep cerebral structures. Thus, the present model could provide a pertinent pre-clinical tool to study gait parameters and their neuronal control but also could be helpful to validate new therapeutics interventions.

Inverse Correlation of Initial CD8 Lymphocyte Count and CD4 Lymphocyte Response to Combination Antiretroviral Therapy in Treatment-naive HIV-infected Patients

Journal of Acquired Immune Deficiency Syndromes (1999). Jan, 2012  |  Pubmed ID: 22156822

Clinical Validation of Movement Disorder Society-recommended Diagnostic Criteria for Parkinson's Disease with Dementia

Movement Disorders : Official Journal of the Movement Disorder Society. Feb, 2012  |  Pubmed ID: 22162144

The objective of this work was to evaluate the Movement Disorders Society (MDS) Task Force-proposed screening checklist for detecting Parkinson's disease dementia (PD-D) in relation to full neuropsychological testing. An MDS Task Force has proposed diagnostic procedures for PD-D, which have not been fully validated against more extensive neuropsychological testing. PD subjects were recruited from 2 specialty centers. A neuropsychologist evaluated them for dementia as part of routine clinical care. Independent clinical neurologists administered the MDS PD-D screening checklist. Diagnosis of PD-D by the 2 methods was compared. Ninety-one PD subjects had a mean age of 66.3 (SD = 9.7) years and a mean PD duration of 8.8 (SD = 6.1) years. Seven subjects (7.7%) met all 8 screening checklist criteria from the MDS PD-D screening tool and were classified as probable PD-D. Fifteen (16.5%) subjects were classified as PD-D by full neuropsychological assessment. The screening checklist showed 100% specificity, but only 46.7% sensitivity, for diagnosing PD-D compared to the full neuropsychological assessment. PD-D cases missed by the PD-D screening tool were largely due to 2 checklist items that were not endorsed (absence of depression and Mini-Mental State Examination [MMSE] scores <26). There was moderate agreement between these 2 methods for determination of PD-D (kappa = 0.59, P < .001). The MDS-PD-D screening checklist is highly accurate for detecting PD-D if all items are endorsed. However, for cases that do not meet these criteria, full neuropsychological testing is needed to differentiate PD-D from milder cognitive impairment. Revision of the checklist by altering or eliminating the 2 problematic checklist items may improve sensitivity.

Development, Characterization, and Applications of a Novel Estrogen Receptor Beta Monoclonal Antibody

Journal of Cellular Biochemistry. Feb, 2012  |  Pubmed ID: 22095450

The role of estrogen receptor alpha (ERα) in breast cancer has been studied extensively, and its protein expression is prognostic and a primary determinant of endocrine sensitivity. However, much less is known about the role of ERβ and its relevance remains unclear due to the publication of conflicting reports. Here, we provide evidence that much of this controversy may be explained by variability in antibody sensitivity and specificity and describe the development, characterization, and potential applications of a novel monoclonal antibody targeting full-length human ERβ and its splice variant forms. Specifically, we demonstrate that a number of commercially available ERβ antibodies are insensitive for ERβ and exhibit significant cross-reaction with ERα. However, our newly developed MC10 ERβ antibody is shown to be highly specific and sensitive for detection of full-length ERβ and its variant forms. Strong and variable staining patterns for endogenous levels of ERβ protein were detected in normal human tissues and breast tumors using the MC10 antibody. Importantly, ERβ was shown to be expressed in a limited cohort of both ERα positive and ERα negative breast tumors. Taken together, these data demonstrate that the use of poorly validated ERβ antibodies is likely to explain much of the controversy in the field with regard to the biological relevance of ERβ in breast cancer. The use of the MC10 antibody, in combination with highly specific antibodies targeting only full-length ERβ, is likely to provide additional discriminatory features in breast cancers that may be useful in predicting response to therapy.

Dopamine Dysregulation Syndrome Item from the MDS-UPDRS

Movement Disorders : Official Journal of the Movement Disorder Society. Jan, 2012  |  Pubmed ID: 22025291

Long-term Outcome for the Surgical Treatment of Infective Endocarditis with a Focus on Intravenous Drug Users

The Annals of Thoracic Surgery. Jan, 2012  |  Pubmed ID: 22054655

We reviewed our experience with surgical procedures for infective endocarditis (IE) in order to evaluate modern outcomes and objectively examine our institutional preferences, including the use of bioprostheses in intravenous drug users (IVDUs) regardless of age and prompt surgical intervention in patients with either septic cerebral emboli or active infection.

Isolation and Molecular Characterization of Rem2 Isoforms in the Rainbow Trout (Oncorhynchus Mykiss): Tissue and Central Nervous System Expression

Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology. Feb, 2012  |  Pubmed ID: 21983188

REM2 is a member of the REM, RAD, and GEM/KIR (RGK) subfamily of RAS superfamily proteins and plays an important role in brain development and function. In this study, two Rem2 isoforms were isolated from the rainbow trout (Oncorhynchus mykiss). The two genes, designated O. mykiss rem2a and rem2b, both encode 304 amino acid proteins with 61% and 62% identities to zebrafish (Danio rerio) Rem2, respectively, and each with 43% identity to mammalian (human) REM2. To our knowledge, this is the first incidence of Rem2 isoforms in a species that are the result of gene duplication. Both isoforms possessed similar tissue expression profiles with the highest levels in the brain. The rem2a gene has significantly higher expression levels than rem2b in all tissues assayed except the brain and head kidney. In the central nervous system, both isoforms showed similar expression levels with the highest levels occurring in the olfactory bulb, cerebrum, and midbrain, though rem2a expression is significantly higher in the spinal cord. Based on known functional roles of Rem2 in synapse development and stem cell proliferation, the characterization of Rem2 in rainbow trout could shed light on its role in adult vertebrate neurogenesis and brain regeneration.

Admission Levels of Soluble CD137 Are Increased in Patients with Acute Pancreatitis and Are Associated with Subsequent Complications

Experimental and Molecular Pathology. Feb, 2012  |  Pubmed ID: 21963611

The progression of acute pancreatitis to necrotizing pancreatitis which often results in high morbidity and mortality is difficult to predict. Here we report that serum concentrations of sCD137 are increased in patients with acute pancreatitis. Admission levels and 10-day median sCD137 levels positively correlate with markers of biliary pancreatitis and the 10-day sCD137 median is significantly higher in metabolic than in alcoholic pancreatitis. Serum concentrations of sCD137 at time of admission and the 10-day median of sCD137 correlate with the Ranson and APACHE II disease scores but not with the radiological Balthazar and Schroeder scores that reflect pancreatic and peripancreatic necrosis. Further, sCD137 levels correlate with the probability of complications and lethality. The association of sCD137, a product of activated T cells, with the severity of acute pancreatitis suggests that T cells contribute to the pathogenesis of acute pancreatitis.

Radiological Diagnosis of Incomplete Partition Type I Versus Type II: Significance for Cochlear Implantation

European Radiology. Mar, 2012  |  Pubmed ID: 21965038

To investigate an extended cohort of patients with incomplete partition (IP) and examine the adequacy of the existing classifications based on radiological criteria and on their implications for cochlear implantation.

The Vestibulocochlear Nerve: Aplasia and Hypoplasia in Combination with Inner Ear Malformations

European Radiology. Mar, 2012  |  Pubmed ID: 21960158

To determine features of hypoplasia and aplasia of the vestibulocochlear nerve (VCN) in combination with inner ear malformations (IEMs).

A Percutaneous Coronary Intervention Lab in Every Hospital?

Circulation. Cardiovascular Quality and Outcomes. Jan, 2012  |  Pubmed ID: 22147882

In 2001, 1176 US hospitals were capable of performing primary percutaneous coronary intervention (PCI), and 79% of the population lived within 60-minute ground transport of these hospitals. We compared these estimates with data from 2006 to explore how hospital PCI capability and population access have changed over time.

Subject-investigator Reproducibility of the Unified Parkinson's Disease Rating Scale

Parkinsonism & Related Disorders. Mar, 2012  |  Pubmed ID: 22018910

To evaluate the subject-investigator agreement on the Unified Parkinson's Disease Rating Scale (UPDRS) subsections I and II.

The Process of Curriculum Development and Implementation for an Adolescent Health Project in Middle Schools

The Journal of School Nursing : the Official Publication of the National Association of School Nurses. Feb, 2012  |  Pubmed ID: 21994321

Childhood obesity has reached epidemic levels in developed countries and is showing no signs of abating. The causes of obesity in adolescence are extremely complex, and therefore approaches to prevention and treatments must be multifaceted. Early adolescence is a developmental period when youth are becoming more independent, are influenced by peers, and are making more decisions related to their own health and lifestyles. The purpose of this article is to describe the development, implementation, and evaluation of a multilevel school-based intervention program for middle school students in the Teen Eating and Activity Mentoring in Schools (TEAMS) project. Critical components of success included an interdisciplinary approach, applying available curricula to meet contextual characteristics, and involvement of all stakeholders in planning, evaluating, and refining the program.

Effect of Acute Posttrauma Propranolol on PTSD Outcome and Physiological Responses During Script-driven Imagery

CNS Neuroscience & Therapeutics. Jan, 2012  |  Pubmed ID: 22070357

Animal and human research suggests that the development of posttraumatic stress disorder (PTSD) may involve the overconsolidation of memories of a traumatic experience. Previous studies have attempted to use pharmaceutical agents, especially the β-adrenergic blocker propranolol, to reduce this overconsolidation.

Self-compassion in Patients with Persistent Musculoskeletal Pain: Relationship of Self-compassion to Adjustment to Persistent Pain

Journal of Pain and Symptom Management. Apr, 2012  |  Pubmed ID: 22071165

Self-compassion entails qualities such as kindness and understanding toward oneself in difficult circumstances and may influence adjustment to persistent pain. Self-compassion may be a particularly influential factor in pain adjustment for obese individuals who suffer from persistent pain, as they often experience heightened levels of pain and lower levels of psychological functioning.

Elevated Vancomycin Trough is Not Associated with Nephrotoxicity Among Inpatient Veterans

Journal of Hospital Medicine : an Official Publication of the Society of Hospital Medicine. Feb, 2012  |  Pubmed ID: 22086511

Vancomycin troughs of 15-20 mg/L are recommended in the treatment of invasive staphylococcal disease, higher levels than previously recommended. OBJECTIVE/SETTING: We sought to determine if there was an association between vancomycin trough and nephrotoxicity, defined as 0.5 mg/L or 50% increase in serum creatinine, at a large Veterans Affairs medical center.