bluuebunny/crossref_metadata_2025 huggingface dataset:
A crucial role for tumor necrosis factor receptor 1 in synovial lining cells and the reticuloendothelial system in mediating experimental arthritis
Authors: Arntz Onno J , Geurts Jeroen , Veenbergen Sharon , Bennink Miranda B , van den Brand Ben T , Abdollahi-Roodsaz Shahla , van den Berg Wim B , van de Loo Fons A
Published: April 2010

Introduction

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that mainly affects synovial joints. Biologics directed against tumor-necrosis-factor (TNF)-α are efficacious in the treatment of RA. However, the role of TNF receptor-1 (TNFR1) in mediating the TNFα effects in RA has not been elucidated and conflicting data exist in experimental arthritis models. The objective is to investigate the role of TNFR1 in the synovial lining cells (SLC) and the reticuloendothelial system (RES) during experimental arthritis.

Methods

Third generation of adenovirus serotype 5 were either injected locally in the knee joint cavity or systemically by intravenous injection into the retro-orbital venous sinus to specifically target SLC and RES, respectively. Transduction of organs was detected by immunohistochemistry of the eGFP transgene. An adenoviral vector containing a short hairpin (sh) RNA directed against TNFR1 (HpTNFR1) was constructed and functionally evaluated in vitro using a nuclear factor-kappaB (NF-κB) reporter assay and in vivo in streptococcal cell wall-induced arthritis (SCW) and collagen-induced arthritis (CIA). Adenoviruses were administered before onset of CIA, and the effect of TNFR1 targeting on the clinical development of arthritis, histology, quantitative polymerase chain reaction (qPCR), cytokine analyses and T-cell assays was evaluated.

Results

Systemic delivery of Ad5.CMV-eGFP predominantly transduced the RES in liver and spleen. Local delivery transduced the synovium and not the RES in liver, spleen and draining lymph nodes. In vitro, HpTNFR1 reduced the TNFR1 mRNA expression by three-fold resulting in a 70% reduction of TNFα-induced NF-κB activation. Local treatment with HpTNFR1 markedly reduced mRNA and protein levels of interleukin (IL)-1β and IL-6 in SLC during SCW arthritis and ameliorated CIA. Systemic targeting of TNFR1 in RES of liver and spleen by systemic delivery of Ad5 virus encoding for a small hairpin RNA against TNFR1 markedly ameliorated CIA and simultaneously reduced the mRNA expression of IL-1β, IL-6 and Saa1 (75%), in the liver and that of Th1/2/17-specific transcription factors T-bet, GATA-3 and RORγT in the spleen. Flow cytometry confirmed that HpTNFR1 reduced the numbers of interferon (IFN)γ (Th1)-, IL-4 (Th2)- and IL-17 (Th17)-producing cells in spleen.

Conclusions

TNFR1-mediated signaling in both synovial lining cells and the reticuloendothelial system independently played a major pro-inflammatory and immunoregulatory role in the development of experimental arthritis.
Preadmission statin use and one-year mortality among patients in intensive care - A cohort study
Authors: Christensen Steffen , Thomsen Reimar W , Johansen Martin B , Pedersen Lars , Jensen Reinhold , Larsen Kim M , Larsson Anders , Tønnesen Else , Sørensen Henrik Toft
Published: April 2010

Introduction

Statins reduce risk of cardiovascular events and have beneficial pleiotropic effects; both may reduce mortality in critically ill patients. We examined whether statin use was associated with risk of death in general intensive care unit (ICU) patients.

Methods

Cohort study of 12,483 critically ill patients > 45 yrs of age with a first-time admission to one of three highly specialized ICUs within the Aarhus University Hospital network, Denmark, between 2001 and 2007. Statin users were identified through population-based prescription databases. We computed cumulative mortality rates 0-30 days and 31-365 days after ICU admission and mortality rate ratios (MRRs), using Cox regression analysis controlling for potential confounding factors (demographics, use of other cardiovascular drugs, comorbidity, markers of social status, diagnosis, and surgery).

Results

1882 (14.3%) ICU patients were current statin users. Statin users had a reduced risk of death within 30 days of ICU admission [users: 22.1% vs. non-users 25.0%; adjusted MRR = 0.76 (95% confidence interval (CI): 0.69 to 0.86)]. Statin users also had a reduced risk of death within one year after admission to the ICU [users: 36.4% vs. non-users 39.9%; adjusted MRR = 0.79 (95% CI: 0.73 to 0.86)]. Reduced risk of death associated with current statin use remained robust in various subanalyses and in an analysis using propensity score matching. Former use of statins and current use of non-statin lipid-lowering drugs were not associated with reduced risk of death.

Conclusions

Preadmission statin use was associated with reduced risk of death following intensive care. The associations seen could be a pharmacological effect of statins, but unmeasured differences in characteristics of statin users and non-users cannot be entirely ruled out.
Revisiting the loading dose of amikacin for patients with severe sepsis and septic shock
Authors: Taccone Fabio Silvio , Laterre Pierre-François , Spapen Herbert , Dugernier Thierry , Delattre Isabelle , Layeux Brice , De Backer Daniel , Wittebole Xavier , Wallemacq Pierre , Vincent Jean-Louis , Jacobs Frédérique
Published: April 2010

Introduction

It has been proposed that doses of amikacin of >15 mg/kg should be used in conditions associated with an increased volume of distribution (Vd), such as severe sepsis and septic shock. The primary aim of this study was to determine whether 25 mg/kg (total body weight) of amikacin is an adequate loading dose for these patients.

Methods

This was an open, prospective, multicenter study in four Belgian intensive care units (ICUs). All consecutive patients with a diagnosis of severe sepsis or septic shock, in whom amikacin treatment was indicated, were included in the study.

Results

In 74 patients, serum samples were collected before (t = 0 h) and 1 hour (peak), 1 hour 30 minutes, 4 hours 30 minutes, 8 hours, and 24 hours after the first dose of amikacin. Blood amikacin levels were measured by using a validated fluorescence polarization immunoassay method, and an open two-compartment model with first-order elimination was fitted to concentrations-versus-time data for amikacin (WinNonlin). In 52 (70%) patients, peak serum concentrations were >64 μg/ml, which corresponds to 8 times the clinical minimal inhibitory concentration (MIC) breakpoints defined by EUCAST for Enterobacteriaceae and Pseudomonas aeruginosa (S<8, R>16 μg/ml). Vd was 0.41 (0.29 to 0.51) L/kg; elimination half-life, 4.6 (3.2 to 7.8) hours; and total clearance, 1.98 (1.28 to 3.54) ml/min/kg. No correlation was found between the amikacin peak and any clinical or hemodynamic variable.

Conclusions

As patients with severe sepsis and septic shock have an increased Vd, a first dose of ≥ 25 mg/kg (total body weight) of amikacin is required to reach therapeutic peak concentrations. However, even with this higher amikacin dose, the peak concentration remained below therapeutic target levels in about one third of these patients. Optimizing aminoglycoside therapy should be achieved by tight serum-concentration monitoring because of the wide interindividual variability of pharmacokinetic abnormalities.
Immunity and other defenses in pea aphids, Acyrthosiphon pisum
Authors: Gerardo Nicole M , Altincicek Boran , Anselme Caroline , Atamian Hagop , Barribeau Seth M , de Vos Martin , Duncan Elizabeth J , Evans Jay D , Gabaldón Toni , Ghanim Murad , Heddi Adelaziz , Kaloshian Isgouhi , Latorre Amparo , Moya Andres , Nakabachi Atsushi , Parker Benjamin J , Pérez-Brocal Vincente , Pignatelli Miguel , Rahbé Yvan , Ramsey John S , Spragg Chelsea J , Tamames Javier , Tamarit Daniel , Tamborindeguy Cecilia , Vincent-Monegat Caroline , Vilcinskas Andreas
Published: April 2010

Background

Recent genomic analyses of arthropod defense mechanisms suggest conservation of key elements underlying responses to pathogens, parasites and stresses. At the center of pathogen-induced immune responses are signaling pathways triggered by the recognition of fungal, bacterial and viral signatures. These pathways result in the production of response molecules, such as antimicrobial peptides and lysozymes, which degrade or destroy invaders. Using the recently sequenced genome of the pea aphid (Acyrthosiphon pisum), we conducted the first extensive annotation of the immune and stress gene repertoire of a hemipterous insect, which is phylogenetically distantly related to previously characterized insects models.

Results

Strikingly, pea aphids appear to be missing genes present in insect genomes characterized to date and thought critical for recognition, signaling and killing of microbes. In line with results of gene annotation, experimental analyses designed to characterize immune response through the isolation of RNA transcripts and proteins from immune-challenged pea aphids uncovered few immune-related products. Gene expression studies, however, indicated some expression of immune and stress-related genes.

Conclusions

The absence of genes suspected to be essential for the insect immune response suggests that the traditional view of insect immunity may not be as broadly applicable as once thought. The limitations of the aphid immune system may be representative of a broad range of insects, or may be aphid specific. We suggest that several aspects of the aphid life style, such as their association with microbial symbionts, could facilitate survival without strong immune protection.
GLP-1(7-36)-amide and Exendin-4 Stimulate the HPA Axis in Rodents and Humans
Authors: Gil-Lozano Manuel , Pérez-Tilve Diego , Alvarez-Crespo Mayte , Martís Aurelio , Fernandez Ana M. , Catalina Pablo A. F. , Gonzalez-Matias Lucas C. , Mallo Federico
Published: April 2010

Glucagon-like peptide-1 (GLP-1) is a potent insulinotropic peptide expressed in the gut and brain, which is secreted in response to food intake. The levels of GLP-1 within the brain have been related to the activity of the hypothalamic-pituitary-adrenal (HPA) axis, and hence, this peptide might mediate some responses to stress. Nevertheless, there is little information regarding the effects of circulating GLP-1 on the neuroendocrine control of HPA activity. Here, we have studied the response of corticoadrenal steroids to the peripheral administration of GLP-1 (7-36)-amide and related peptides [exendin (Ex)-3, Ex-4, and Ex-4(3-39)] in rats, mice, and humans. GLP-1 increases circulating corticosterone levels in a time-dependent manner, both in conscious and anaesthetized rats, and it has also increased aldosterone levels. Moreover, GLP-1 augmented cortisol levels in healthy subjects and diabetes mellitus (DM)-1 patients. The effects of GLP-1/Ex-4 on the HPA axis are very consistent after distinct means of administration (intracerebroventricular, iv, and ip), irrespective of the metabolic state of the animals (fasting or fed ad libitum), and they were reproduced by different peptides in this family, independent of glycaemic changes and their insulinotropic properties. Indeed, these effects were also observed in diabetic subjects (DM-1 patients) and in the DM-1 streptozotocin-rat or DM-2 muscle IGF-I receptor-lysine-arginine transgenic mouse animal models. The mechanisms whereby circulating GLP-1 activates the HPA axis remain to be elucidated, although an increase in ACTH after Ex-4 and GLP-1 administration implicates the central nervous system or a direct effect on the pituitary. Together, these findings suggest that GLP-1 may play an important role in regulating the HPA axis.
Inflammatory Markers Are Increased in Youth with Type 1 Diabetes: The SEARCH Case-Control Study
Authors: Snell-Bergeon Janet K. , West Nancy A. , Mayer-Davis Elizabeth J. , Liese Angela D. , Marcovina Santica M. , D'Agostino Ralph B. , Hamman Richard F. , Dabelea Dana
Published: April 2010

Context: Increased inflammation may contribute to type 1 diabetes (T1D) complications.

Objective: The objective of the study was to investigate the association of inflammation with obesity, hyperglycemia and dyslipidemia in youth with T1D.

Design: This was a cross-sectional study of youth with and without T1D.

Setting: The study was conducted in Colorado and South Carolina.

Patients: SEARCH Case-Control participants with T1D [n = 553, mean age 15 yr (range 10–22), median duration 2.7 yr] and without diabetes [n = 215, mean age 15 yr (range 10–22)].

Intervention: This was an observational study.

Main Outcome Measures: IL-6, high-sensitivity C-reactive protein (hsCRP), fibrinogen, and leptin were measured.

Results: Inflammatory markers were evaluated by diabetes status, quartiles of glycated hemoglobin, and obesity using multiple linear regression analyses, adjusted for age, sex, study site, race/ethnicity, T1D duration, body mass index, and pubertal status. Compared with controls, youth with T1D had higher IL-6 and fibrinogen levels at all levels of glycemia and obesity, and hsCRP levels were significantly higher in youth with T1D in the top three quartiles of glycated hemoglobin (≥7.2%) and among normal-weight subjects. Leptin was lower in youth with poor glycemic control. Higher hsCRP and fibrinogen were correlated with higher total and LDL cholesterol, and apolipoprotein B in youth with T1D, whereas higher fibrinogen was correlated with higher LDL and apolipoprotein B in controls.

Conclusions: T1D is characterized by excess inflammation, independent of adiposity and glycemic control. Even T1D youth in good glycemic control had higher levels of IL-6 and fibrinogen than controls. Elevated inflammatory markers were associated with an atherogenic lipid profile, which may contribute to accelerated atherosclerosis in youth with T1D.
Subtle Cognitive Impairments in Patients with Long-Term Cure of Cushing’s Disease
Authors: Tiemensma Jitske , Kokshoorn Nieke E. , Biermasz Nienke R. , Keijser Bart-Jan S. A. , Wassenaar Moniek J. E. , Middelkoop Huub A. M. , Pereira Alberto M. , Romijn Johannes A.
Published: April 2010

Context and Objective: Active Cushing’s disease is associated with cognitive impairments. We hypothesized that previous hypercortisolism in patients with Cushing’s disease results in irreversible impairments in cognitive functioning. Therefore, our aim was to assess cognitive functioning after long-term cure of Cushing’s disease.

Design: Cognitive assessment consisted of 11 tests, which evaluated global cognitive functioning, memory, and executive functioning.

Patients and Control Subjects: We included 74 patients cured of Cushing’s disease and 74 controls matched for age, gender, and education. Furthermore, we included 54 patients previously treated for nonfunctioning pituitary macroadenomas (NFMA) and 54 controls matched for age, gender, and education.

Results: Compared with NFMA patients, patients cured from Cushing’s disease had lower scores on the Mini Mental State Examination (P = 0.001), and on the memory quotient of the Wechsler Memory Scale (P = 0.050). Furthermore, patients cured from Cushing’s disease tended to recall fewer words on the imprinting (P = 0.013), immediate recall (P = 0.012), and delayed recall (P = 0.003) trials of the Verbal Learning Test of Rey. On the Rey Complex Figure Test, patients cured from Cushing’s disease had lower scores on both trials (P = 0.002 and P = 0.007) compared with NFMA patients. Patients cured from Cushing’s disease also made fewer correct substitutions on the Letter-Digit Substitution Test (P = 0.039) and came up with fewer correct patterns on the Figure Fluency Test (P = 0.003) compared with treated NFMA patients.

Conclusions: Cognitive function, reflecting memory and executive functions, is impaired in patients despite long-term cure of Cushing’s disease. These observations indicate irreversible effects of previous hypercortisolism on cognitive function and, thus, on the central nervous system. These observations may also be of relevance for patients treated with high-dose exogenous glucocorticoids.
Glucocorticoid Receptor Gene, Low-Grade Inflammation, and Heart Failure: The Heart and Soul Study
Authors: Otte Christian , Wüst Stefan , Zhao Shoujun , Pawlikowska Ludmila , Kwok Pui-Yan , Whooley Mary A.
Published: April 2010

Context: A common haplotype of the glucocorticoid receptor (GR) gene has been associated with increased susceptibility to coronary heart disease (CHD). Whether this haplotype predisposes to heart failure (HF) is unknown.

Objective: The objective of the study was to determine whether GR haplotype 3 is associated with HF and whether this association is explained by low-grade inflammation (C-reactive protein).

Design: In a prospective cohort study, participants were genotyped for common GR gene polymorphisms (ER22/23EK, BclI C/G, N363S, 9β A/G). Haplotype analyses were conducted.

Setting: The study was conducted at one university medical center, two Veterans Affairs medical centers, and nine public health clinics.

Patients: Patients included 526 white outpatients with stable CHD.

Main Outcome Measures: Echocardiographic evidence of ventricular dysfunction, self-reported heart failure, and subsequent hospitalization for heart failure were measured.

Results: After adjusting for age, sex, smoking, and body mass index, participants with two copies of haplotype 3 were more likely than those with 0 or 1 copy to report heart failure [hazard ratio (HR) 4.15, 95% confidence interval (CI) 1.5–11.3, P < 0.01], have systolic dysfunction (left ventricular ejection fraction <50%) (HR 3.0, 95% CI 0.9–9.9, P = 0.07), and be hospitalized for HF during a mean follow-up of 6 yr (HR 3.0, 95% CI 1.3–7.0, P = 0.01). These associations were attenuated after adjustment for higher C-reactive protein levels in patients with two copies of haplotype 3.

Conclusions: We found that the GR gene haplotype 3 was associated with prevalent HF, systolic dysfunction, and subsequent HF hospitalization in patients with CHD. This association was partly mediated by low-grade inflammation.
Basal Follicle-Stimulating Hormone and Peak Gonadotropin Levels after Gonadotropin-Releasing Hormone Infusion Show High Diagnostic Accuracy in Boys with Suspicion of Hypogonadotropic Hypogonadism
Authors: Grinspon Romina P. , Ropelato María Gabriela , Gottlieb Silvia , Keselman Ana , Martínez Alicia , Ballerini María Gabriela , Domené Horacio M. , Rey Rodolfo A.
Published: April 2010

Context: Differential diagnosis between hypogonadotropic hypogonadism (HH) and constitutional delay of puberty in boys is challenging. Most tests use an acute GnRH stimulus, allowing only the release of previously synthesized gonadotropins. A constant GnRH infusion, inducing de novo gonadotropin synthesis, may allow a better discrimination.

Objective: We evaluated the diagnostic accuracy of basal and peak gonadotropins after GnRH infusion, measured by ultrasensitive assays, to confirm the diagnosis in boys with suspected HH.

Design and Setting: We conducted a validation study following Standards for Reporting of Diagnostic Accuracy criteria at a tertiary public hospital.

Patients and Methods: A GnRH iv infusion test was performed in 32 boys. LH and FSH were determined by immunofluorometric assay at 0–120 min.

Diagnosis Ascertainment: The following diagnoses were ascertained: complete HH (n = 19; testes < 4 ml at 18 yr), partial HH (n = 6; testes enlargement remained arrested for ≥1 yr or did not reach 15 ml), and constitutional delay of puberty (n = 7; testes ≥ 15 ml at 18 yr).

Main Outcome Measures: Sensitivity, specificity, positive and negative predictive values, and diagnostic efficiency were assessed.

Results: Basal FSH less than 1.2 IU/liter confirmed HH with specificity of 1.00 (95% confidence interval = 0.59–1.00), rendering GnRH infusion unnecessary. In patients with basal FSH of at least 1.2 IU/liter, the coexistence of peak FSH less than 4.6 IU/liter and peak LH less than 5.8 IU/liter after GnRH infusion had high specificity (1.00; 95% confidence interval = 0.59–1.00) and diagnostic efficiency (76.9%) for HH.

Conclusions: Basal FSH less than 1.2 IU/liter confirms HH, which precludes from further testing, reducing patient discomfort and healthcare system costs. In patients with basal FSH of at least 1.2 IU/liter, a GnRH infusion test has a high diagnostic efficiency.
Gaming of performance measurement in health care: Parallels with tax compliance
Authors: Mears Alex , Webley Paul
Published: April 2010

Gaming of performance measurement in health care distorts performance, making it appear better than it is. This can conceal potentially hazardous practice and endanger patients and staff. Research has investigated and categorized this behaviour but as yet has offered little in the way of potential solutions as the drivers are still not well understood. Studies of the psychology of tax behaviour, specifically tax avoidance and evasion, reveal some insights into what the underlying causes are. Looking at health care and tax compliance, seven similarities in response can be detected: negative view of those subject to it; not salient except for specific classes of people; general understanding of the need versus resentment of actuality; cognitive dissonance; moral versus legal grey areas; two levels of objective non-compliance; and four categories of subjective behaviour and attitude. We suggest a model of reaction and compliance for gaming and offer some suggestions as to how this phenomenon might be minimized.
Improvement in Appropriate Utilization of Recombinant Human Erythropoietin Pre- and Post-Implementation of a Required Order Form
Authors: Burns Tammy L , Ferry Brenna A , Malesker Mark A , Morrow Lee E , Bruckner Anne L , Lee Debra L
Published: April 2010

BACKGROUND:

Erythropoietin stimulating agents (ESAs) are high-cost medications that have a significant impact on many pharmacy budgets. Recently, ESAs have received stronger safety warnings and reimbursement has been curtailed by third-party payers including the Centers for Medicare and Medicaid Services. For these reasons, many hospitals are developing strategies to optimize their use. A required order form with acceptable indications and dosing was implemented at an academic medical center in an attempt to improve dosing and appropriate utilization of ESAs.

OBJECTIVE:

To determine whether implementation of a required order form increased appropriate use and/or decreased total utilization of recombinant human erythropoietin (rHuEPO).

METHODS:

This was a retrospective cohort study of rHuEPO utilization for 4 months pre- and 6 months post-implementation (April 2008-January 2009).

RESULTS:

Implementation of a required order form for rHuEPO resulted in significantly fewer patients receiving inappropriate doses of rHuEPO (51.3% vs 19.2%, p < 0.001). The number of patients treated, adjusted to hospital census, was also reduced after implementation of the order form (0.003 vs 0.004 pts./average pt. days, p = 0.03). Annual spending for rHuEPO was reduced by 47% during 2008 despite an increased acquisition cost.

CONCLUSIONS:

Implementation of a required order form with evidence-based dosing recommendations can be an effective strategy to improve appropriate utilization of rHuEPO.
Association of Pancreatitis with Glucagon-Like Peptide-1 Agonist Use
Authors: Anderson Sarah L , Trujillo Jennifer M
Published: April 2010

OBJECTIVE:

To review the possible association between glucagon-like peptide-1 (GLP-1) agonist use and pancreatitis in patients with type 2 diabetes mellitus.

DATA SOURCES:

A MEDLINE search (1950-January 2010) identified key clinical trials delineating adverse effects associated with GLP-1 agonist use. Key search terms included type 2 diabetes mellitus, pancreatitis, incretins, exenatide, liraglutide, albiglutide, and taspoglutide. Review of references listed in the articles identified was also performed. The Food and Drug Administration (FDA) Web site and Amylin Pharmaceuticals file data were utilized to extract case report information and unpublished clinical development data related to GLP-1 agonist use and pancreatitis.

STUDY SELECTION AND DATA EXTRACTION:

Phase 2 and 3 clinical trials evaluating exenatide, liraglutide, albiglutide, and taspoglutide that discussed treatment-related adverse effects as well as FDA-reviewed case reports of pancreatitis in patients taking these same therapies were included. One study evaluating type 2 diabetes as a risk factor for development of acute pancreatitis was also included. Exenatide case reports and clinical development data were also included.

DATA SYNTHESIS:

Currently there have been 8 cases during clinical development and 36 postmarketing reports of acute pancreatitis in exenatide-treated patients. Four patients have developed acute (n = 3) or chronic (1) pancreatitis during liraglutide clinical trials. There have been no reports to date of development of acute pancreatitis in patients taking albiglutide or taspoglutide.

CONCLUSIONS:

Observational reports and clinical trial data suggest an association between GLP-1 agonist use and acute pancreatitis; however, additional clinical trial data and in-depth case report analysis are needed to further evaluate and verify this finding.
Use of Information Technology in Medication Reconciliation: A Scoping Review
Authors: Bassi Jesdeep , Lau Francis , Bardal Stan
Published: April 2010

OBJECTIVE:

To identify studies involving information technology (IT) in medication reconciliation (MedRec) and determine how IT is used to facilitate the MedRec process.

DATA SOURCES:

The search strategy included a database search of MEDLINE and Cumulative Index of Nursing and Allied Health Literature (CINAHL), hand-searching of collected material, and references from articles retrieved. The database search was limited to English-language papers. MEDLINE includes publications dating back to 1950 and CINAHL includes those dating back to 1982. The search included articles in both databases up to March 2009. Boolean queries were constructed using combinations of search terms for medication reconciliation, IT, and electronic records.

STUDY SELECTION AND DATA EXTRACTION:

Three inclusion criteria were used. The study had to (1) involve the MedRec process, (2) be a primary study, and (3) involve the use of IT. Selection was performed by 2 reviewers through consensus. Data related to study characteristics, focus, and IT use were extracted.

DATA SYNTHESIS:

The included studies described a range of IT used throughout the MedRec process, from basic email and databases to specialized MedRec tools. A generic MedRec workflow was created and types of IT found in the studies were mapped to the workflow activities as well as to a set of functionalities based on the Institute of Medicine's Key Capabilities of an Electronic Health Record System. In the studies reviewed, IT was mainly used to obtain medication information. Although there were only a few MedRec tools in the studies, those that did exist supported the central activities for MedRec: comparison of medications and clarification of discrepancies.

CONCLUSIONS:

MedRec is an important process to ensure patient medication safety. Evidence was found that IT can and has been used to facilitate some MedRec activities and new applications are being developed to support the entire MedRec process.
Not Silent, Invisible: Literature’s Chance Encounters with Deaf Heroes and Heroines
Authors: McDonald Donna M.
Published: March 2010

Literature is both a rich resource and a blunt instrument in conveying the complexities of identity, in particular, the elusive deaf identity . The rarity of the fully realized deaf person in memoir and fiction shapes the way readers regard deaf people and throws up fresh challenges in redesigning stories of deafness free of the taint of triumphalism or complaint. Competing but authentic representations of deafness and deaf people’s experiences allow readers to variously witness, immerse themselves in, and navigate their way through those experiences. Consequently, establishing universal truths about deaf lives is a risky business and an improbable goal.
Deaf Epistemology: The Deaf Way of Knowing
Authors: Holcomb Thomas K.
Published: March 2010

The standard epistemology requires the use of hard science to gain knowledge and discover the truth. In contrast, Deaf epistemology relies heavily on personal testimonies, personal experiences, and personal accounts to document knowledge. In recent years, a number of deaf schools have adopted deaf-centric policies shaped by Deaf epistemology in an effort to improve academic performance of deaf students. Because of federal laws, all schools are now expected to show accountability in the performance of their students, with data becoming increasingly available for public scrutiny. The preliminary data from three well-known deaf schools are beginning to show that the effectiveness of deaf-centric approaches can be substantiated by the standard epistemology. For this reason, Deaf epistemology and the standard epistemology should not always be viewed as having an oxymoronic relationship.
Epistemologies, Deafness, Learning, and Teaching
Authors: Moores Donald F.
Published: March 2010

The study of Deaf epistemologies is in a nascent stage relative to, e.g., the study of feminist or African American epistemologies. It has only recently begun attracting the widespread attention it deserves. The present article addresses Deaf epistemologies as they relate to the sometimes conflicting trends in American society and education. In a relatively short period, the education of deaf students has gone from an independent enterprise under the aegis of special education to heavy influence by No Child Left Behind legislation that applies to virtually all American students. American education at one and the same time embraces and celebrates diversity, imposes uniform, rigid learning standards for all children, and mandates that all children be tested in the same way. An oxymoron exists of individualized educational planning and one-size-fits-all curricula and assessment of academic achievement. Implications for teaching and learning of deaf students are explored.
The Qualitative Similarity Hypothesis
Authors: Paul Peter V. , Lee Chongmin
Published: March 2010

Evidence is presented for the qualitative similarity hypothesis (QSH) with respect to children and adolescents who are d/Deaf or hard of hearing. The primary focus is on the development of English language and literacy skills, and some information is provided on the acquisition of English as a second language. The QSH is briefly discussed within the purview of two groups of cognitive models: those that emphasize the cognitive development of individuals and those that pertain to disciplinary or knowledge structures. It is argued that the QSH has scientific merit with implications for classroom instruction. Future research should examine the validity of the QSH in other disciplines such as mathematics and science and should include perspectives from social as well as cognitive models.
Launching Native Health Leaders: Students as Community–Campus Ambassadors
Authors: Segrest Valerie , James Rosalina , Madrid Teresa , Fernandes Roger
Published: April 2010

Background: Ancient teaching styles such as storytelling can help Native students to navigate the educational pipeline, and become forces for shaping health and research landscapes. Many experience isolation on campuses where these worldviews are marginalized. Objective: Launching Native Health Leaders (LNHL) reduces academic isolation by creating an environment where students identify with Native values while exposing them to health and research career opportunities and interdisciplinary professional and community networks. Student experiences and the LNHL mentoring approach are described through phases of the Hero's Journey, a universal mythic story of human struggle and transformation. Methods: Undergraduates were recruited to attend health and research conferences through college and university student service programs. Tribal community representatives led group discussions focused on tribal health issues, and students explored intersections of indigenous knowledge with community-based participatory research (CBPR) and their educational journeys. Results: LNHL supported more than sixty students to attend eight professional conferences since 2006 that included themes of cancer control, tribal wellness, and indigenous knowledge systems for health. Students pursuing higher degrees and community service careers participated in conference sessions, small group discussions, and reflection activities with professional and tribal community mentors. Conclusion: Mainstream academic systems must include indigenous voices at all levels of leadership to shift the direction of health trends. LNHL builds capacity for community-based efforts by balancing Indigenous and academic mentoring and empowering Native students to navigate their personal journeys and create pathways to serve the needs of Indigenous peoples. Students from other marginalized groups may benefit from an LNHL mentoring approach.
The William Schuman Violin Concerto: Genesis of a Twentieth-Century Masterpiece
Authors: Polisi Joseph W.
Published: March 2010

The saga of the composition and revisions of William Schuman's Violin Concerto spans approximately fourteen years, from 1946 to 1959. The genesis of this work represents a rare and lengthy process for Schuman. Evidence in his letters and oral histories, a close examination of the extensive manuscript and audio sources of the concerto's three versions, and a consideration of the composer's overall musical output during this time period provide an intriguing look into the mind of Schuman as he composed this most affecting work. In his Violin Concerto Schuman combines his skills as a symphonist and his knowledge of the violin to create a work of pathos, passion, and drive that showcases the virtuosic and expressive qualities of the solo instrument. In particular, Schuman liberates the solo violin line from the harmonic underpinnings in the orchestra, allowing the principal melodic elements of the concerto, as heard in the solo violin, to float above the accompaniment. Schuman's extensive editing of the work gives it a focus and passion that merits consideration of the Violin Concerto as one of his most successful and masterfully composed works and one of the finest violin concertos of the twentieth century.
Under Civilian Colonels:Indigenous Political Mobilization in 1920s Ayacucho, Peru
Authors: Heilman Jaymie Patricia
Published: March 2010

With his television blaring in the corner, Don Isidro Durán spoke of the men whom his neighbors had once chosen as leaders, men those neighbors labeled “colonels.” As Don Isidro described the indigenous political mobilization that rocked his rural Ayacucho community back in 1923, he explained that these colonels led their supporters in military exercises and proclaimed that President Augusto B. Leguía was “bad for the Pueblo.” Although the elderly Durán spoke with the authority of an eyewitness and the eloquence of a local intellectual, the indigenous leaders he described are essentially absent from the extensive literature on indigenous politics during Peru's 1920s. That absence is surprising, for reports of various popularly appointed colonels fill Ayacucho's archival records during Leguia'soncenio(his 1919-1930 presidency). These Ayacuchano civilian colonels were typically literate, indigenous men witxiout formal standing in the Peruvian armed forces. During the first years of the 1920s, Ayacucho peasants embraced rliese indigenous men as leaders because of their profound anger at official government authorities and their agents.
Chinese by Definition: Nationality Law, Jus Sanguinis, and State Succession, 1909-1980
Authors: Shao Dan
Published: March 2010

This article examines the historical roots, social implications, and inherent paradoxes of jus sanguinis-a legal principle that uses blood lineage to defines one's nationality-during the years of state succession in twentieth-century China. The study begins with a discussion of why the Qing dynasty established the first Chinese nationality law and chose jus sanguinis over jus soli at a time when anti-Manchu ethno-nationalism was on the rise. Qing lawmakers imported and invoked jus sanguinis not to define an exclusive or homogeneous nationhood, but to maintain individuals' perpetual allegiance to the state. In periods of state succession, legal cases involving nationality law reveal the paradoxes inherent in defining Chinese national membership and loyalty by bloodline, though the principle itself is practiced as if objective. Today, jus sanguinis still defines Chinese nationality and requires nationals' loyalty to China, with unintended, problematical consequences for people from border-crossing communities and historical borderlands.
Actin-mediated gene expression in neurons: the MRTF-SRF connection
Authors: Knöll Bernd
Published: April 2010

The traditional view of cellular actin is a rather autarkic cytoskeletal framework function confined to the cytoplasm. However, there is now evidence that alterations in actin dynamics are sensed by the nucleus and subsequently modulate gene expression. In communicating with the nucleus, cytoplasmic, and most likely also nucleus-resident actin, provides a further (gene) regulatory loop to cell motility. A transcription module composed of MRTF (myocardin-related transcription factor) and SRF (serum response factor) emerges as prime target of such actin signaling. Here, I focus on the nervous system, where the actin-MRTF-SRF entity governs multiple aspects of neuronal motility.
Contributions of the Ah receptor to bilirubin homeostasis and its antioxidative and atheroprotective functions
Authors: Bock Karl Walter , Köhle Christoph
Published: April 2010

The homeostasis and atheroprotective function of bilirubin could be an appealing model to investigate one of the many physiologic functions of the human aryl hydrocarbon receptor (AhR). Several clinical and epidemiological studies have been carried out on key enzymes generating and eliminating bilirubin (heme oxygenase-1 and UDP-glucuronosyltransferase UGT1A1, respectively) and their regulation by the AhR. Studies with AhR-deficient mice strongly suggest a role of the AhR in vascular biology. Atherosclerosis, a major cause of premature death, is initiated by pro-oxidative insults of the vascular endothelium. The strong antioxidant and activator of AhR bilirubin is generated in vascular endothelial cells, smooth muscles and macrophages. It acts mostly in the lipid environment, thereby complementing other antioxidants such as glutathione which act mostly on water-soluble proteins. In conclusion, the atheroprotective functions of bilirubin might not only provide models to study physiologic functions of the human AhR but also provide opportunities to improve prevention and treatment of a major life-threatening disease.
Functional study of elafin cleaved by Pseudomonas aeruginosa metalloproteinases
Authors: Guyot Nicolas , Bergsson Gudmundur , Butler Marcus W. , Greene Catherine M. , Weldon Sinéad , Kessler Efrat , Levine Rodney L. , O'Neill Shane J. , Taggart Clifford C. , McElvaney Noel G.
Published: April 2010

Elafin is a 6-kDa innate immune protein present at several epithelial surfaces including the pulmonary epithelium. It is a canonical protease inhibitor of two neutrophil serine proteases [neutrophil elastase (NE) and proteinase 3] with the capacity to covalently bind extracellular matrix proteins by transglutamination. In addition to these properties, elafin also possesses antimicrobial and immunomodulatory activities. The aim of the present study was to investigate the effect ofPseudomonas aeruginosaproteases on elafin function. We found thatP. aeruginosaPAO1-conditioned medium and two purifiedPseudomonasmetalloproteases, pseudolysin (elastase) and aeruginolysin (alkaline protease), are able to cleave recombinant elafin. Pseudolysin was shown to inactivate the anti-NE activity of elafin by cleaving its protease-binding loop. Interestingly, antibacterial properties of elafin against PAO1 were found to be unaffected after pseudolysin treatment. In contrast to pseudolysin, aeruginolysin failed to inactivate the inhibitory properties of elafin against NE. Aeruginolysin cleaves elafin at the amino-terminal Lys6-Gly7 peptide bond, resulting in a decreased ability to covalently bind purified fibronectin following transglutaminase activity. In conclusion, this study provides evidence that elafin is susceptible to proteolytic cleavage at alternative sites byP. aeruginosametalloproteinases, which can affect different biological functions of elafin.
Synaptic Tagging and Capture: Differential Role of Distinct Calcium/Calmodulin Kinases in Protein Synthesis-Dependent Long-Term Potentiation
Authors: Redondo Roger L. , Okuno Hiroyuki , Spooner Patrick A. , Frenguelli Bruno G. , Bito Haruhiko , Morris Richard G. M.
Published: April 2010

Weakly tetanized synapses in area CA1 of the hippocampus that ordinarily display long-term potentiation lasting ∼3 h (called early-LTP) will maintain a longer-lasting change in efficacy (late-LTP) if the weak tetanization occurs shortly before or after strong tetanization of an independent, but convergent, set of synapses in CA1. The synaptic tagging and capture hypothesis explains this heterosynaptic influence on persistence in terms of a distinction between local mechanisms of synaptic tagging and cell-wide mechanisms responsible for the synthesis, distribution, and capture of plasticity-related proteins (PRPs). We now present evidence that distinct CaM kinase (CaMK) pathways serve a dissociable role in these mechanisms. Using a hippocampal brain-slice preparation that permits stable long-term recordingsin vitrofor >10 h and using hippocampal cultures to validate the differential drug effects on distinct CaMK pathways, we show that tag setting is blocked by the CaMK inhibitor KN-93 (2-[N-(2-hydroxyethyl)]-N-(4-methoxybenzenesulfonyl)amino-N-(4-chlorocinnamyl)-N-methylbenzylamine) that, at low concentration, is more selective for CaMKII. In contrast, the CaMK kinase inhibitor STO-609 [7H-benzimidazo(2,1-a)benz(de)isoquinoline-7-one-3-carboxylic acid] specifically limits the synthesis and/or availability of PRPs. Analytically powerful three-pathway protocols using sequential strong and weak tetanization in varying orders and test stimulation over long periods of time after LTP induction enable a pharmacological dissociation of these distinct roles of the CaMK pathways in late-LTP and so provide a novel framework for the molecular mechanisms by which synaptic potentiation, and possibly memories, become stabilized.
Development of Global Cortical Networks in Early Infancy
Authors: Homae Fumitaka , Watanabe Hama , Otobe Takayuki , Nakano Tamami , Go Tohshin , Konishi Yukuo , Taga Gentaro
Published: April 2010

Human cognition and behaviors are subserved by global networks of neural mechanisms. Although the organization of the brain is a subject of interest, the process of development of global cortical networks in early infancy has not yet been clarified. In the present study, we explored developmental changes in these networks from several days to 6 months after birth by examining spontaneous fluctuations in brain activity, using multichannel near-infrared spectroscopy. We set up 94 measurement channels over the frontal, temporal, parietal, and occipital regions of the infant brain. The obtained signals showed complex time-series properties, which were characterized as 1/ffluctuations. To reveal the functional connectivity of the cortical networks, we calculated the temporal correlations of continuous signals between all the pairs of measurement channels. We found that the cortical network organization showed regional dependency and dynamic changes in the course of development. In the temporal, parietal, and occipital regions, connectivity increased between homologous regions in the two hemispheres and within hemispheres; in the frontal regions, it decreased progressively. Frontoposterior connectivity changed to a “U-shaped” pattern within 6 months: it decreases from the neonatal period to the age of 3 months and increases from the age of 3 months to the age of 6 months. We applied cluster analyses to the correlation coefficients and showed that the bilateral organization of the networks begins to emerge during the first 3 months of life. Our findings suggest that these developing networks, which form multiple clusters, are precursors of the functional cerebral architecture.
Membrane-Associated Glucocorticoid Activity Is Necessary for Modulation of Long-Term Memory via Chromatin Modification
Authors: Roozendaal Benno , Hernandez Angelina , Cabrera Sara M. , Hagewoud Roelina , Malvaez Melissa , Stefanko Daniel P. , Haettig Jakob , Wood Marcelo A.
Published: April 2010

Glucocorticoid hormones enhance the consolidation of long-term memory of emotionally arousing training experiences. This memory enhancement requires activation of the cAMP-dependent kinase pathway and the subsequent phosphorylation of cAMP response-element binding (CREB) protein. Here, we demonstrate that glucocorticoids enhance the consolidation of hippocampus-dependent and hippocampus-independent aspects of object recognition memory via chromatin modification. More specifically, systemic corticosterone increases histone acetylation, a form of chromatin modification, in both the hippocampus and insular cortex following training on an object recognition task. This led us to examine whether increasing histone acetylation via histone deacetylase (HDAC) inhibition enhances memory in a manner similar to corticosterone. We found a double dissociation between posttraining HDAC inhibitor infusion into the insular cortex and hippocampus on the enhancement of object recognition and object location memory, respectively. In determining the molecular pathway upstream of glucocorticoids' effects on chromatin modification, we found that activation of membrane-associated glucocorticoid receptors (GRs) and the subsequent interaction between phospho-CREB and CREB-binding protein (CBP) appear to be necessary for glucocorticoids to enhance memory consolidation via chromatin modification. In contrast, mineralocorticoid receptors (MRs) do not appear to be involved. The findings also indicate that glucocorticoid activity has differential influences on hippocampus-dependent and hippocampus-independent components of memory for objects.
A Mouse Model of Amyloid β Oligomers: Their Contribution to Synaptic Alteration, Abnormal Tau Phosphorylation, Glial Activation, and Neuronal LossIn Vivo
Authors: Tomiyama Takami , Matsuyama Shogo , Iso Hiroyuki , Umeda Tomohiro , Takuma Hiroshi , Ohnishi Kiyouhisa , Ishibashi Kenichi , Teraoka Rie , Sakama Naomi , Yamashita Takenari , Nishitsuji Kazuchika , Ito Kazuhiro , Shimada Hiroyuki , Lambert Mary P. , Klein William L. , Mori Hiroshi
Published: April 2010

Although amyloid β (Aβ) oligomers are presumed to cause synaptic and cognitive dysfunction in Alzheimer's disease (AD), their contribution to other pathological features of AD remains unclear. To address the latter, we generated APP transgenic mice expressing the E693Δ mutation, which causes AD by enhanced Aβ oligomerization without fibrillization. The mice displayed age-dependent accumulation of intraneuronal Aβ oligomers from 8 months but no extracellular amyloid deposits even at 24 months. Hippocampal synaptic plasticity and memory were impaired at 8 months, at which time the presynaptic marker synaptophysin began to decrease. Furthermore, we detected abnormal tau phosphorylation from 8 months, microglial activation from 12 months, astrocyte activation from 18 months, and neuronal loss at 24 months. These findings suggest that Aβ oligomers cause not only synaptic alteration but also other features of AD pathology and that these mice are a useful model of Aβ oligomer-induced pathology in the absence of amyloid plaques.