bluuebunny/crossref_metadata_2025 huggingface dataset:
Communicative Daily Life Stories and Focus Groups: Proposals for Overcoming Gender Violence Among Teenagers
Authors: Aubert Adriana , Melgar Patricia , Valls Rosa
Published: February 2011

The scientific literature has identified an attraction toward models of masculinity marked by abuse and domination in teenagers’ sexual and affective relationships. Given this reality, greater insight is needed on the mechanisms that lead young people to choose this type of relationship. In theory, different authors argue that as a result of the disassociation between goodness and attractiveness a profound crisis of meaning is found. A study conducted with the Critical Communicative Methodology, particularly, through the use of communicative data collection techniques has led to gather evidences of this crisis, particularly how it is interplayed by the opposition between a language of ethics versus a language of desire. The use of communicative daily life stories and communicative focus groups allowed not only to identify this separation but also those elements that contribute to overcome it.
Higher and lower virtues in commercial society
Authors: Herzog Lisa
Published: February 2011

Motivation crowding out can lead to a reduction of ‘higher’ virtues, such as altruism or public spirit, in market contexts. This article discusses the role of virtue in the moral and economic theory of Adam Smith. It argues that because Smith’s account of commercial society is based on ‘lower’ virtue, ‘higher’ virtue has a precarious place in it; this phenomenon is structurally similar to motivation crowding out. The article analyzes and systematizes the ways in which Smith builds on ‘contrivances of nature’ in order to solve the problems of limited self-command and limited knowledge. As recent research has shown, a clear separation of different social spheres can help to reduce the risk of motivation crowding out and preserve a place for ‘higher virtue’ in commercial society. The conclusion reflects on the performative power of economics, arguing that the one-sided focus on models of ‘economic man’ should be embedded in a larger context.
Communicating About Loss: Experiences of Older Australian Adults With Cerebral Palsy and Complex Communication Needs
Authors: Dark Leigha , Balandin Susan , Clemson Lindy
Published: February 2011

Loss and grief is a universal human experience, yet little is known about how older adults with a lifelong disability, such as cerebral palsy, and complex communication needs (CCN) experience loss and manage the grieving process. In-depth interviews were conducted with 20 Australian participants with cerebral palsy and CCN to determine the types of loss experienced by this group in their later years, sources of support available to manage loss, and the role of communication as a barrier or facilitator to a successful grieving process. The results are discussed in light of current grief and loss theory, and clinical implications and opportunities for further research are suggested.
Using the Communication Matrix to Assess Expressive Skills in Early Communicators
Authors: Rowland Charity
Published: February 2011

Many children born with severe and multiple disabilities have complex communication needs and may use no speech or only minimal speech to communicate. Meaningful assessment of their expressive skills to identify communication strengths along a developmental trajectory is an essential first step toward appropriate intervention. This article describes the foundations, structure, properties, and use of the Communication Matrix, an assessment instrument developed specifically to address the challenges of describing the expressive communication skills of children with severe and multiple disabilities. The widely used online version of this assessment tool collects data in an associated database. Sample data on children with specific disabilities generated by this database are presented to illustrate the clinical and research potential of this free assessment service.
Health Beliefs and Their Associations With Dietary Intake, Exercise, and Metabolic Syndrome Characteristics in an Overweight and Obese Family Medicine Population
Authors: Edman Joel S. , Diamond James J. , Wortman Jeremy , Carballo-Sayao Laura
Published: February 2011

Increasing prevalences of obesity and type 2 diabetes (T2DM) increase cardiovascular risks. Since poor diet and inadequate exercise are primary behavioral causes of obesity and T2DM, our objective was to examine health beliefs and associations with diet, exercise, and metabolic syndrome (MetSyndr) characteristics. A total of 117 overweight and obese family medicine patients enrolled in this study. Subjects completed questionnaires for health beliefs and vegetable, fruit, and fat intake; other data were from medical charts. Seventy-four percent of subjects were women; 69% were black, 72% were obese, 36% were hypertensive, 22% had T2DM, and 23% had hypertriglyceridemia. MetSyndr subjects had significantly higher triglyceride levels and a higher percentage of hypertension and T2DM. Although not statistically significant, overweight subjects without MetSyndr had higher vegetable and fruit intake and lower fat intake than obese subjects without MetSyndr and subjects with MetSyndr. More exercise was associated with less MetSyndr and less obesity; however, this also was not statistically significant. For health beliefs, there were no significant differences between subjects with MetSyndr versus those without MetSyndr or for subjects without MetSyndr who were obese versus those who were overweight. However, for subjects with above-median nutrition scores and exercise, scores were significantly higher for the health belief “certainty” compared to those with below-median scores ( P < .0001). This research suggests that health beliefs and specifically less certainty may be a useful marker for individuals who require more education and/or training. Effective programs that address certainty may promote better diets, more exercise, and reduced cardiovascular risk.
The Role of Community Health Workers in Combating Type 2 Diabetes in the Rio Grande Valley
Authors: Ryabov Igor , Richardson Chad
Published: February 2011

The purpose of this study was to determine the effectiveness of the use of community health workers (CHWs, aka promotoras de salud in Spanish) in the control of type 2 diabetes (diabetes mellitus) in the Rio Grande Valley (RGV). Known from the literature as “a disease of the 21st century” and being the third leading cause of death in the United States, type 2 diabetes is a very common disease in the RGV because of its predominantly Mexican American population, a group genetically vulnerable to the disease. Unlike prior studies that examined the overall effectiveness of the CHW model, the authors used registered CHWs as primary diabetes educators. Another innovation of this study was the authors monitored a wide range of biologic (HbA1c and body mass index [BMI]) and behavioral (diabetes knowledge, self-efficacy, self-management activities scores) outcomes. The research hypothesis was that the educational service provided by CHWs to the diabetic patients would assist them in controlling their disease. The design of the study was experimental. The target population consisted of Mexican American adults from RGV diagnosed with type 2 diabetes and willing to participate. The intervention group received monthly visits from CHWs. The results showed a significant improvement after one year of intervention in all outcomes, except BMI, in the experimental group.
MYB transcriptionally regulates the miR-155 host gene in chronic lymphocytic leukemia
Authors: Vargova Karin , Curik Nikola , Burda Pavel , Basova Petra , Kulvait Vojtech , Pospisil Vit , Savvulidi Filipp , Kokavec Juraj , Necas Emanuel , Berkova Adela , Obrtlikova Petra , Karban Josef , Mraz Marek , Pospisilova Sarka , Mayer Jiri , Trneny Marek , Zavadil Jiri , Stopka Tomas
Published: February 2011

Elevated levels of microRNA miR-155 represent a candidate pathogenic factor in chronic B-lymphocytic leukemia (B-CLL). In this study, we present evidence that MYB (v-myb myeloblastosis viral oncogene homolog) is overexpressed in a subset of B-CLL patients. MYB physically associates with the promoter of miR-155 host gene (MIR155HG, also known as BIC, B-cell integration cluster) and stimulates its transcription. This coincides with the hypermethylated histone H3K4 residue and spread hyperacetylation of H3K9 at MIR155HG promoter. Our data provide evidence of oncogenic activities of MYB in B-CLL that include its stimulatory role in MIR155HG transcription.
Telomerase reverse transcriptase protects ATM-deficient hematopoietic stem cells from ROS-induced apoptosis through a telomere-independent mechanism
Authors: Nitta Eriko , Yamashita Masayuki , Hosokawa Kentaro , Xian MingJi , Takubo Keiyo , Arai Fumio , Nakada Shinichiro , Suda Toshio
Published: February 2011

Telomerase reverse transcriptase (TERT) contributes to the prevention of aging by a largely unknown mechanism that is unrelated to telomere lengthening. The current study used ataxia-telangiectasia mutated (ATM) and TERT doubly deficient mice to evaluate the contributions of 2 aging-regulating molecules, TERT and ATM, to the aging process. ATM and TERT doubly deficient mice demonstrated increased progression of aging and had shorter lifespans than ATM-null mice, while TERT alone was insufficient to affect lifespan. ATM-TERT doubly null mice show in vivo senescence, especially in hematopoietic tissues, that was dependent on p16INK4a and p19ARF, but not on p21. As their HSCs show decreased stem cell activities, accelerated aging seen in these mice has been attributed to impaired stem cell function. TERT-deficient HSCs are characterized by reactive oxygen species (ROS) fragility, which has been suggested to cause stem cell impairment during aging, and apoptotic HSCs are markedly increased in these mice. p38MAPK activation was indicated to be partially involved in ROS-induced apoptosis in TERT-null HSCs, and BCL-2 is suggested to provide a part of the protective mechanisms of HSCs by TERT. The current study demonstrates that TERT mitigates aging by protecting HSCs under stressful conditions through telomere length-independent mechanisms.
RNAi screen of the druggable genome identifies modulators of proteasome inhibitor sensitivity in myeloma including CDK5
Authors: Zhu Yuan Xiao , Tiedemann Rodger , Shi Chang-Xin , Yin Holly , Schmidt Jessica E. , Bruins Laura A. , Keats Jonathan J. , Braggio Esteban , Sereduk Chris , Mousses Spyro , Stewart A. Keith
Published: February 2011

The molecular target(s) cooperating with proteasome inhibition in multiple myeloma (MM) remain unknown. We therefore measured proliferation in MM cells transfected with 13 984 small interfering RNAs in the absence or presence of increasing concentrations of bortezomib. We identified 37 genes, which when silenced, are not directly cytotoxic but do synergistically potentiate the growth inhibitory effects of bortezomib. To focus on bortezomib sensitizers, genes that also sensitized MM to melphalan were excluded. When suppressed, the strongest bortezomib sensitizers were the proteasome subunits PSMA5, PSMB2, PSMB3, and PSMB7 providing internal validation, but others included BAZ1B, CDK5, CDC42SE2, MDM4, NME7, RAB8B, TFE3, TNFAIP3, TNK1, TOP1, VAMP2, and YY1. The strongest hit CDK5 also featured prominently in pathway analysis of primary screen data. Cyclin-dependent kinase 5 (CDK5) is expressed at high levels in MM and neural tissues with relatively low expression in other organs. Viral shRNA knockdown of CDK5 consistently sensitized 5 genetically variable MM cell lines to proteasome inhibitors (bortezomib and carfilzomib). Small-molecule CDK5 inhibitors were demonstrated to synergize with bortezomib to induce cytotoxicity of primary myeloma cells and myeloma cell lines. CDK5 regulation of proteasome subunit PSMB5 was identified as a probable route to sensitization.
Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1
Authors: Rajkumar S. Vincent , Harousseau Jean-Luc , Durie Brian , Anderson Kenneth C. , Dimopoulos Meletios , Kyle Robert , Blade Joan , Richardson Paul , Orlowski Robert , Siegel David , Jagannath Sundar , Facon Thierry , Avet-Loiseau Hervé , Lonial Sagar , Palumbo Antonio , Zonder Jeffrey , Ludwig Heinz , Vesole David , Sezer Orhan , Munshi Nikhil C. , San Miguel Jesus ,   on behalf of the International Myeloma Workshop Consensus Panel 1
Published: February 2011

It is essential that there be consistency in the conduct, analysis, and reporting of clinical trial results in myeloma. The goal of the International Myeloma Workshop Consensus Panel 1 was to develop a set of guidelines for the uniform reporting of clinical trial results in myeloma. This paper provides a summary of the current response criteria in myeloma, detailed definitions for patient populations, lines of therapy, and specific endpoints. We propose that future clinical trials in myeloma follow the guidelines for reporting results proposed in this manuscript.
Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3
Authors: Dimopoulos Meletios , Kyle Robert , Fermand Jean-Paul , Rajkumar S. Vincent , San Miguel Jesus , Chanan-Khan Asher , Ludwig Heinz , Joshua Douglas , Mehta Jayesh , Gertz Morie , Avet-Loiseau Hervé , Beksaç Meral , Anderson Kenneth C. , Moreau Philippe , Singhal Seema , Goldschmidt Hartmut , Boccadoro Mario , Kumar Shaji , Giralt Sergio , Munshi Nikhil C. , Jagannath Sundar ,   on behalf of the International Myeloma Workshop Consensus Panel 3
Published: February 2011

A panel of members of the 2009 International Myeloma Workshop developed guidelines for standard investigative workup of patients with suspected multiple myeloma. Both serum and urine should be assessed for monoclonal protein. Measurement of monoclonal protein both by densitometer tracing and/by nephelometric quantitation is recommended, and immunofixation is required for confirmation. The serum-free light chain assay is recommended in all newly diagnosed patients with plasma cell dyscrasias. Bone marrow aspiration and/or biopsy along with demonstration of clonality of plasma cells are necessary. Serum β2-microglobulin, albumin, and lactate dehydrogenase are necessary for prognostic purposes. Standard metaphase cytogenetics and fluorescent in situ hybridization for 17p, t(4;14), and t(14;16) are recommended. The skeletal survey remains the standard method for imaging screening, but magnetic resonance imaging frequently provides valuable diagnostic and prognostic information. Most of these tests are repeated during follow-up or at relapse.
Deciphering the molecular and biologic processes that mediate histone deacetylase inhibitor–induced thrombocytopenia
Authors: Bishton Mark J. , Harrison Simon J. , Martin Benjamin P. , McLaughlin Nicole , James Chloé , Josefsson Emma C. , Henley Katya J. , Kile Benjamin T. , Prince H. Miles , Johnstone Ricky W.
Published: February 2011

Histone deacetylase inhibitor (HDACI)–induced thrombocytopenia (TCP) is a major dose-limiting toxicity of this new class of drugs. Using preclinical models to study the molecular and biologic events that underpin this effect of HDACI, we found that C57BL/6 mice treated with both the HDAC1/2-selective HDACI romidepsin and the pan-HDACI panobinostat developed significant TCP. HDACI-induced TCP was not due to myelosuppression or reduced platelet lifespan, but to decreased platelet release from megakaryocytes. Cultured primary murine megakaryocytes showed reductions in proplatelet extensions after HDACI exposure and a dose-dependent increase in the phosphorylation of myosin light chain 2 (MLC2). Phosphorylation of MLC to phospho-MLC (pMLC) and subsequent proplatelet formation in megakaryocytes is regulated by the Rho-GTPase proteins Rac1, CDC42, and RhoA. Primary mouse megakaryocytes and the human megakaryoblastic cell line Meg-01 showed reductions in Rac1, CDC42, and RhoA protein levels after treatment with HDACIs. We were able to overcome HDACI-induced TCP by administering the mouse-specific thrombopoietin (TPO) mimetic AMP-4, which improved platelet numbers to levels similar to untreated controls. Our report provides the first detailed account of the molecular and biologic processes involved in HDACI-mediated TCP. Moreover, our preclinical studies provide evidence that dose-limiting TCP induced by HDACIs may be circumvented using a TPO mimetic.
Phenotypic characteristics of human type II alveolar epithelial cells suitable for antigen presentation to T lymphocytes
Authors: Corbière Véronique , Dirix Violette , Norrenberg Sarah , Cappello Mattéo , Remmelink Myriam , Mascart Françoise
Published: February 2011

Background

Type II alveolar epithelial cells (AECII) are well known for their role in the innate immune system. More recently, it was proposed that they could play a role in the antigen presentation to T lymphocytes but contradictory results have been published both concerning their surface expressed molecules and the T lymphocyte responses in mixed lymphocyte cultures. The use of either AECII cell line or fresh cells could explain the observed discrepancies. Thus, this study aimed at defining the most relevant model of accessory antigen presenting cells by carefully comparing the two models for their expression of surface molecules necessary for efficient antigen presentation.

Methods

We have compared by flow cytometry the surface expression of the major markers involved in the immunological synapse on the A549 cell line, the most popular model of type II alveolar epithelial cells, and freshly isolated cells. HLA-DR, CD80, CD86, ICOS-L, CD54, CD58 surface expression were studied in resting conditions as well as after IFN-γ/TNF-α treatment, two inflammatory cytokines, known to modulate some of these markers.

Results

The major difference found between the two cells types was the very low surface expression of HLA-DR on the A549 cell line compared to its constitutive expression on freshly isolated AECII. The surface expression of co-stimulatory molecules from the B7 family was very low for the CD86 (B7-2) and ICOS-L (B7-H2) and absent for CD80 (B7-1) on both freshly isolated cells and A549 cell line. Neither IFN-γ nor TNF-α could increase the expression of these classical co-stimulatory molecules. However CD54 (ICAM-1) and CD58 (LFA-3) adhesion molecules, known to be implicated in B7 independent co-stimulatory signals, were well expressed on the two cell types.

Conclusions

Constitutive expression of MHC class I and II molecules as well as alternative co-stimulatory molecules by freshly isolated AECII render these cells a good model to study antigen presentation.
Evaluation of four novel genetic variants affecting hemoglobin A1c levels in a population-based type 2 diabetes cohort (the HUNT2 study)
Authors: Hertel Jens K , Johansson Stefan , Ræder Helge , Platou Carl GP , Midthjell Kristian , Hveem Kristian , Molven Anders , Njølstad Pål R
Published: February 2011

Background

Chronic hyperglycemia confers increased risk for long-term diabetes-associated complications and repeated hemoglobin A1c (HbA1c) measures are a widely used marker for glycemic control in diabetes treatment and follow-up. A recent genome-wide association study revealed four genetic loci, which were associated with HbA1c levels in adults with type 1 diabetes. We aimed to evaluate the effect of these loci on glycemic control in type 2 diabetes.

Methods

We genotyped 1,486 subjects with type 2 diabetes from a Norwegian population-based cohort (HUNT2) for single-nucleotide polymorphisms (SNPs) located near the BNC2, SORCS1, GSC and WDR72 loci. Through regression models, we examined their effects on HbA1c and non-fasting glucose levels individually and in a combined genetic score model.

Results

No significant associations with HbA1c or glucose levels were found for the SORCS1, BNC2, GSC or WDR72 variants (all P-values > 0.05). Although the observed effects were non-significant and of much smaller magnitude than previously reported in type 1 diabetes, the SORCS1 risk variant showed a direction consistent with increased HbA1c and glucose levels, with an observed effect of 0.11% (P = 0.13) and 0.13 mmol/l (P = 0.43) increase per risk allele for HbA1c and glucose, respectively. In contrast, the WDR72 risk variant showed a borderline association with reduced HbA1c levels (β = -0.21, P = 0.06), and direction consistent with decreased glucose levels (β = -0.29, P = 0.29). The allele count model gave no evidence for a relationship between increasing number of risk alleles and increasing HbA1c levels (β = 0.04, P = 0.38).

Conclusions

The four recently reported SNPs affecting glycemic control in type 1 diabetes had no apparent effect on HbA1c in type 2 diabetes individually or by using a combined genetic score model. However, for the SORCS1 SNP, our findings do not rule out a possible relationship with HbA1c levels. Hence, further studies in other populations are needed to elucidate whether these novel sequence variants, especially rs1358030 near the SORCS1 locus, affect glycemic control in type 2 diabetes.
An integrative pharmacological approach to radio telemetry and blood sampling in pharmaceutical drug discovery and safety assessment
Authors: Litwin Dennis C , Lengel David J , Kamendi Harriet W , Bialecki Russell A
Published: February 2011

Background

A successful integration of the automated blood sampling (ABS) and telemetry (ABST) system is described. The new ABST system facilitates concomitant collection of physiological variables with blood and urine samples for determination of drug concentrations and other biochemical measures in the same rat without handling artifact.

Method

Integration was achieved by designing a 13 inch circular receiving antenna that operates as a plug-in replacement for the existing pair of DSI's orthogonal antennas which is compatible with the rotating cage and open floor design of the BASi Culex® ABS system. The circular receiving antenna's electrical configuration consists of a pair of electrically orthogonal half-toroids that reinforce reception of a dipole transmitter operating within the coil's interior while reducing both external noise pickup and interference from other adjacent dipole transmitters.

Results

For validation, measured baclofen concentration (ABST vs. satellite (μM): 69.6 ± 23.8 vs. 76.6 ± 19.5, p = NS) and mean arterial pressure (ABST vs. traditional DSI telemetry (mm Hg): 150 ± 5 vs.147 ± 4, p = NS) variables were quantitatively and qualitatively similar between rats housed in the ABST system and traditional home cage approaches.

Conclusion

The ABST system offers unique advantages over traditional between-group study paradigms that include improved data quality and significantly reduced animal use. The superior within-group model facilitates assessment of multiple physiological and biochemical responses to test compounds in the same animal. The ABST also provides opportunities to evaluate temporal relations between parameters and to investigate anomalous outlier events because drug concentrations, physiological and biochemical measures for each animal are available for comparisons.
Plasma peptidome profiling of acute hepatitis E patients by MALDI-TOF/TOF
Authors: Taneja Shikha , Ahmad Imran , Sen Somdutta , Kumar Saravanan , Arora Reena , Gupta Vijay K , Aggarwal Rakesh , Narayanasamy Krishnamoorthy , Reddy Vanga S , Jameel Shahid
Published: February 2011

Background

Hepatitis E is endemic to resource-poor regions, where it manifests as sporadic cases and large waterborne outbreaks. The disease severity ranges from acute self-limited hepatitis with low mortality to fulminant hepatic failure with high mortality. It is believed that the host response plays an important role in determining the progression and outcome of this disease. We profiled the plasma peptidome from hepatitis E patients to discover suitable biomarkers and understand disease pathogenesis.

Results

The peptidome (< 10 kDa) fraction of plasma was enriched and analyzed by mass spectrometry. A comparative analysis of the peptide pattern of hepatitis E patients versus healthy controls was performed using ClinPro Tools. We generated a peptide profile that could be used for selective identification of hepatitis E cases. We have identified five potential biomarker peaks with m/z values of 9288.6, 7763.6, 4961.5, 1060.572 and 2365.139 that can be used to reliably differentiate between hepatitis E patients and controls with areas under the receiver operating characteristic curve (AUROC) values of 1.00, 0.954, 0.989, 0.960 and 0.829 respectively. A number of proteins involved in innate immunity were identified to be differentially present in the plasma of patients compared to healthy controls.

Conclusions

Besides the utility of this approach for biomarker discovery, identification of changes in endogenous peptides in hepatitis E patient plasma has increased our understanding of disease pathogenesis. We have identified peptides in plasma that can reliably distinguish hepatitis E patients from healthy controls. Results from this and an earlier proteomics study are discussed.
Myocardium-derived conditioned medium improves left ventricular function in rodent acute myocardial infarction
Authors: Leu Steve , Kao Ying-Hsien , Sun Cheuk-Kwan , Lin Yu-Chun , Tsai Tzu-Hsien , Chang Li-Teh , Chua Sarah , Yeh Kuo-Ho , Wu Chiung-Jen , Fu Morgan , Yip Hon-Kan
Published: February 2011

Background

We investigated whether myocardium-derived conditioned medium (MDCM) is effective in preserving left ventricular (LV) function in a rat acute myocardial infarction (AMI) model.

Methods

Adult male Sprague-Dawley (SD) rats (n = 36) randomized to receive either left coronary artery ligation (AMI induction) or thoracotomy only (sham procedure) were grouped as follows (n = 6 per group): Group I, II, and III were sham-controls treated by fresh medium, normal rat MDCM, and infarct-related MDCM, respectively. Group IV, V, and VI were AMI rats treated by fresh medium, normal MDCM, and infarct-related MDCM, respectively. Either 75 μL MDCM or fresh medium was administered into infarct myocardium, followed by intravenous injection (3 mL) at postoperative 1, 12, and 24 h.

Results

In vitro studies showed higher phosphorylated MMP-2 and MMP-9, but lower α-smooth muscle actin and collagen expressions in neonatal cardiac fibroblasts treated with MDCM compared with those in the cardiac fibroblasts treated with fresh medium (all p < 0.05). Sirius-red staining showed larger collagen deposition area in LV myocardium in Group IV than in other groups (all p < 0.05). Stromal cell-derived factor-1α and CXCR4 protein expressions were higher in Group VI than in other groups (all p < 0.05). The number of von Willebrand factor- and BrdU-positive cells and small vessels in LV myocardium as well as 90-day LV ejection fraction were higher, whereas oxidative stress was lower in Group VI than in Group IV and Group V (all p < 0.05).

Conclusion

MDCM therapy reduced cardiac fibrosis and oxidative stress, enhanced angiogenesis, and preserved 90-day LV function in a rat AMI model.
Scanning Probe Microscopy on heterogeneous CaCu3Ti4O12 thin films
Authors: Fiorenza Patrick , Lo Nigro Raffaella , Raineri Vito
Published: February 2011

The conductive atomic force microscopy provided a local characterization of the dielectric heterogeneities in CaCu3Ti4O12 (CCTO) thin films deposited by MOCVD on IrO2 bottom electrode. In particular, both techniques have been employed to clarify the role of the inter- and sub-granular features in terms of conductive and insulating regions. The microstructure and the dielectric properties of CCTO thin films have been studied and the evidence of internal barriers in CCTO thin films has been provided. The role of internal barriers and the possible explanation for the extrinsic origin of the giant dielectric response in CCTO has been evaluated.
Impact of crisis resolution and home treatment teams on
psychiatric admissions in England
Authors: Jacobs R. , Barrenho E.
Published: February 2011

Background

In 2000/01 crisis resolution and home treatment (CRHT) teams were
introduced in England and have been associated in previous studies with
reductions in in-patient admissions.

Aims

To examine whether the implementation of CRHT teams has been associated
with reductions in admissions.

Method

We used data from a previous national study for 229 primary care trusts
(PCTs) between 1998/99 and 2003/04. We used a robust policy evaluation
methodology to simultaneously examine temporal changes (PCTs before
versus after the introduction of CRHT teams) and cross-sectional changes
(PCTs with and without CRHT teams).

Results

Controlling for various confounding factors, using different control
groups and estimation methods, we find no significant differences in
admissions between PCTs with and without CRHT teams.

Conclusions

Contrary to previous studies, we find no evidence that the CRHT policy
per se has made any difference to admissions and
suggest a need for more research on the policy as a whole.
Unrecognised bipolar disorder in primary care patients with
depression
Authors: Smith Daniel J. , Griffiths Emily , Kelly Mark , Hood Kerry , Craddock Nick , Simpson Sharon A.
Published: February 2011

Background

Bipolar disorder is complex and can be difficult to diagnose. It is often
misdiagnosed as recurrent major depressive disorder.

Aims

We had three main aims. To estimate the proportion of primary care
patients with a working diagnosis of unipolar depression who satisfy
DSM–IV criteria for bipolar disorder. To test two screening instruments
for bipolar disorder (the Hypomania Checklist (HCL–32) and Bipolar
Spectrum Diagnostic Scale (BSDS)) within a primary care sample. To assess
whether individuals with major depressive disorder with subthreshold
manic symptoms differ from those individuals with major depressive
disorder but with no or little history of manic symptoms in terms of
clinical course, psychosocial functioning and quality of life.

Method

Two-phase screening study in primary care.

Results

Three estimates of the prevalence of undiagnosed bipolar disorder were
obtained: 21.6%, 9.6% and 3.3%. The HCL–32 and BSDS questionnaires had
quite low positive predictive values (50.0 and 30.1% respectively).
Participants with major depressive disorder and with a history of
subthreshold manic symptoms differed from those participants with no or
little history of manic symptoms on several clinical features and on
measures of both psychosocial functioning and quality of life.

Conclusions

Between 3.3 and 21.6% of primary care patients with unipolar depression
may have an undiagnosed bipolar disorder. The HCL–32 and BSDS screening
questionnaires may be more useful for detecting broader definitions of
bipolar disorder than DSM–IV-defined bipolar disorder. Subdiagnostic
features of bipolar disorder are relatively common in primary care
patients with unipolar depression and are associated with a more morbid
course of illness. Future classifications of recurrent depression should
include dimensional measures of bipolar symptoms.
Progestogen-Only Contraceptives and the Risk of Acute Myocardial Infarction: A Meta-Analysis
Authors: Chakhtoura Zeina , Canonico Marianne , Gompel Anne , Scarabin Pierre-Yves , Plu-Bureau Geneviève
Published: February 2011

Context:

The association between combined oral contraceptives (OC) and the risk of myocardial infarction (MI) has been intensively studied, and conclusions are controversial. While progestogen-only contraceptives (POC) are commonly used worldwide, their impact on cardiovascular diseases is poorly investigated and remains unclear.

Objective:

We carried out a meta-analysis based on EMBASE- and MEDLINE-referenced literature corresponding to OC marketed since 1960.

Methods:

Eligible articles published in English language describing OC or POC use and MI outcome were reviewed, and relevant ones were extracted. All types of POC and route of administration were considered.

Results:

Six case-control studies were identified. The combined odds ratio showed no increase in the MI risk with POC use (odds ratio = 1.07; 95% confidence interval, 0.62–1.84). This result was similar according to the route of administration, including implant, injectable, and oral POC.

Conclusion:

Data from observational studies suggest no increase in risk of MI with POC use. However, these results are based on limited data. Further investigations are needed, especially among women at high MI risk.
Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Severe Hypoglycemia Complicating Type 2 Diabetes: The Fremantle Diabetes Study
Authors: Davis Wendy A. , Brown Simon G. A. , Jacobs Ian G. , Bulsara Max , Beilby John , Bruce David G. , Davis Timothy M. E.
Published: February 2011

Aims/hypotheses:

The aim of this study was to determine whether the angiotensin-converting enzyme (ACE) gene I/D polymorphisms independently predict severe hypoglycemia in community-dwelling type 2 patients.

Methods:

Six hundred and two patients who were ACE genotyped at baseline and assessed in 1998 were followed up to the end of June 2006. Severe hypoglycemia was defined as that requiring documented health service use as the primary diagnosis. Cox proportional hazards modeling was used to determine the predictors of first episode and zero-inflated negative binomial regression modeling identified predictors of frequency.

Results:

Forty-nine patients (8.1%) experienced 63 episodes of severe hypoglycemia. After adjusting for previously identified significant independent predictors of time to first episode, both ACE DD genotype and ACE inhibitor therapy, but not their interaction, added to the model [hazard ratio (95% confidence interval): 2.34 (1.29–4.26), P = 0.006, and 1.77 (0.99–3.13), P = 0.052, respectively]. Similarly, after adjusting for previously identified risk factors for multiple episodes of severe hypoglycemia, ACE DD genotype was independently associated with increased risk [incidence relative risk (95% confidence interval): 1.80 (1.00–3.24), P = 0.050].

Conclusions/interpretation:

ACE DD genotype was associated with an approximately 2-fold increased risk of the first episode of severe hypoglycemia and its subsequent frequency in well-characterized patients with type 2 diabetes. Consistent with previous case-control studies, ACE inhibitor therapy was a weak predictor of severe hypoglycemia. ACE I/D genotyping might provide useful adjunctive prognostic information when intensive glycemic control measures are contemplated.
Postnatal Decrease in Circulating Insulin-Like Growth Factor-I and Low Brain Volumes in Very Preterm Infants
Authors: Hansen-Pupp Ingrid , Hövel Holger , Hellström Ann , Hellström-Westas Lena , Löfqvist Chatarina , Larsson Elna-Marie , Lazeyras Francois , Fellman Vineta , Hüppi Petra S. , Ley David
Published: February 2011

Context:

IGF-I and IGF binding protein-3 (IGFBP-3) are essential for growth and maturation of the developing brain.

Objective:

The aim of this study was to evaluate the association between postnatal serum concentrations of IGF-I and IGFBP-3 and brain volumes at term in very preterm infants.

Design:

Fifty-one infants with a mean (sd) gestational age (GA) of 26.4 (1.9) wk and birth weight (BW) of 888 (288) g were studied, with weekly blood sampling of IGF-I and IGFBP-3 from birth until 35 gestational weeks (GW) and daily calculation of protein and caloric intake. Magnetic resonance images obtained at 40 GW were segmented into total brain, cerebellar, cerebrospinal fluid, gray matter, and unmyelinated white matter volumes.

Main Outcome Measures:

We evaluated brain growth by measuring brain volumes using magnetic resonance imaging.

Results:

Mean IGF-I concentrations from birth to 35 GW correlated with total brain volume, unmyelinated white matter volume, gray matter volume, and cerebellar volume [r = 0.55 (P < 0.001); r = 0.55 (P < 0.001); r = 0.44 (P = 0.002); and r = 0.58 (P < 0.001), respectively]. Similar correlations were observed for IGFBP-3 concentrations. Correlations remained after adjustment for GA, mean protein and caloric intakes, gender, severe brain damage, and steroid treatment. Protein and caloric intakes were not related to brain volumes. Infants with BW small for GA had lower mean concentrations of IGF-I (P = 0.006) and smaller brain volumes (P = 0.001–0.013) than infants with BW appropriate for GA.

Conclusion:

Postnatal IGF-I and IGFBP-3 concentrations are positively associated with brain volumes at 40 GW in very preterm infants. Normalization of the IGF-I axis, directly or indirectly, may support normal brain development in very preterm infants.
TNF Is Necessary for Castration-Induced Prostate Regression, Whereas TRAIL and FasL Are Dispensable
Authors: Davis Jennifer S. , Nastiuk Kent L. , Krolewski John J.
Published: February 2011

TNF, a proinflammatory and immune-regulatory cytokine, is a potent apoptotic stimulus in vitro. However, there have been few examples of a physiologic role for TNF-induced apoptosis in vivo. Here, we describe a novel role for TNF in prostate epithelial cell apoptosis after androgen withdrawal. Employing high-resolution serial magnetic resonance imaging to measure mouse prostate volume changes over time, we demonstrate that the extent of castration-induced prostate regression is significantly reduced in mice null for either the Tnf or Tnfr1 genes but not mice deficient for TNF-related apoptosis-inducing ligand or Fas signaling. Wild-type mice receiving soluble TNF (sTNF) receptor 2 (to bind TNF and block signaling) before castration exhibit an identical reduction of prostate regression. Together, these data indicate that uniquely among known extrinsic death signals, TNF is required for castration-induced prostate regression. Additionally, membrane-bound TNF protein and stromal cell specific TNF mRNA levels increase in rat prostate after castration. This is consistent with a paracrine role for TNF in prostate regression. When injected into the peritoneum of Tnf−/− mice at the time of castration, sTNF restores normal levels of prostate regression. However, wild-type mice receiving sTNF in the absence of castration do not exhibit prostate regression, indicating that TNF alone is not sufficient but acts in the context of additional castration-induced signals. These findings support a physiologic role for TNF in prostate regression after androgen withdrawal. Understanding this role may lead to novel therapies for prostate cancer.
Species-Specific Strategies Underlying Conserved Functions of Metabolic Transcription Factors
Authors: Soccio Raymond E. , Tuteja Geetu , Everett Logan J. , Li Zhaoyu , Lazar Mitchell A. , Kaestner Klaus H.
Published: February 2011

The winged helix protein FOXA2 and the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) are highly conserved, regionally expressed transcription factors (TFs) that regulate networks of genes controlling complex metabolic functions. Cistrome analysis for Foxa2 in mouse liver and PPARγ in mouse adipocytes has previously produced consensus-binding sites that are nearly identical to those used by the corresponding TFs in human cells. We report here that, despite the conservation of the canonical binding motif, the great majority of binding regions for FOXA2 in human liver and for PPARγ in human adipocytes are not in the orthologous locations corresponding to the mouse genome, and vice versa. Of note, TF binding can be absent in one species despite sequence conservation, including motifs that do support binding in the other species, demonstrating a major limitation of in silico binding site prediction. Whereas only approximately 10% of binding sites are conserved, gene-centric analysis reveals that about 50% of genes with nearby TF occupancy are shared across species for both hepatic FOXA2 and adipocyte PPARγ. Remarkably, for both TFs, many of the shared genes function in tissue-specific metabolic pathways, whereas species-unique genes fail to show enrichment for these pathways. Nonetheless, the species-unique genes, like the shared genes, showed the expected transcriptional regulation by the TFs in loss-of-function experiments. Thus, species-specific strategies underlie the biological functions of metabolic TFs that are highly conserved across mammalian species. Analysis of factor binding in multiple species may be necessary to distinguish apparent species-unique noise and reveal functionally relevant information.
Excited-State Hydrogen and Dihydrogen Bonding of a Dihydrogen-Bonded Phenol–Borane–Dimethylamine Complex
Authors: Liu Yufang , Yang Yonggang , Jiang Kai , Shi Deheng , Sun Jinfeng
Published: February 2011

The excited-state hydrogen and dihydrogen bonding of a dihydrogen-bonded phenol–borane–dimethylamine (BDMA) complex was investigated theoretically by use of time-dependent density functional theory (TDDFT). The coexistence of an intermolecular dihydrogen bond (B–H···H–O) and hydrogen bond (N–H···O) was confirmed by the optimized geometric structure of the dihydrogen-bonded phenol–BDMA complex. The infrared spectra for both the ground and excited states of the dihydrogen-bonded phenol–BDMA complex were also calculated by use of density functional theory (DFT)/TDDFT. As a result, we demonstrated theoretically that the intermolecular dihydrogen bonds B–H···H–O can be significantly strengthened in the excited state. However, the intermolecular hydrogen bond N–H···O in the dihydrogen-bonded phenol–BDMA complex is weakened upon photoexcitation to the S1 state. The dynamic changes of the intermolecular dihydrogen and hydrogen bonding are consistent with the calculated bond lengths in different electronic states. The coexistent dihydrogen and hydrogen bonding in the electronic excited states of this dihydrogen-bonded complex was studied theoretically in this work. Furthermore, it was found that the N–H···O hydrogen bond in the cyclic structure of phenol–BDMA complex hindered the dehydrogenation reaction between dihydrogen bonded O–H and B–H1 groups, which has been reported for the phenol–borane–trimethylamine complex.
A comparison of methods for the measurement of 8-isoPGF2α: a marker of oxidative stress
Authors: Smith K A , Shepherd J , Wakil A , Kilpatrick E S
Published: February 2011

Background

Oxidative stress describes the cellular damage caused by excess reactive oxygen species not adequately inactivated by antioxidants. Oxidative stress has been implicated in playing a role in many disorders. Lipid peroxidation end-products are employed as markers of oxidative stress, of which the isoprostane, 8-iso-PGF2 α, is widely used. 8-iso-PGF2 α is measured in plasma or urine by gas chromatography–mass spectrometry (GC/MS), liquid chromatography–mass spectrometry (LC/MS), tandem-mass spectrometry or enzyme-linked immunosorbent assay (ELISA). However, discrepancies between the specificity of these methods means correlation is poor.

Methods

A tandem-mass spectrometric (LC/MS/MS) method, using immunoaffinity purification, for urinary 8-iso-PGF2 α was developed and compared with two commercial ELISAs (A – Cayman Chemicals, B – Oxford Biomedical Research) in urine samples ( n = 156).

Results

An LC/MS/MS method coupled to immunoaffinity purification was developed with satisfactory performance and comparison to ELISAs A and B. Spearman rank correlation demonstrated significant correlation between all methods ( P = <0.0001); however, r2 values ranged from 0.68 to 0.72. Bland–Altman plots revealed a proportional positive bias of ELISA B when compared with ELISA A and LC/MS/MS. Furthermore, the agreement between ELISA A and LC/MS/MS was poor.

Conclusions

The poor agreement between methods for measurement of 8-iso-PGF2 α highlights differences in selectivity. 8-iso-PGF2 α is an isoprostane, a family of isomeric end-products of arachidonic acid peroxidation, which are produced by peroxidation or enzymatically. This makes avoiding cross-reactivity between 8-iso-PGF2 α and related isomers challenging. When assessing oxidative stress studies, the selectivity of the methods used should be taken into account, particularly when comparing studies.
Zolpidem: Restless Legs Syndrome
Authors: Generali Joyce A. , Cada Dennis J.
Published: February 2011

This Hospital Pharmacy feature is extracted from Off-Label Drug Facts, a quarterly publication available from Wolters Kluwer Health. Off-Label Drug Facts is a practitioner-oriented resource for information about specific drug uses that are unapproved by the US Food and Drug Administration. This new guide to the literature enables the health care professional or clinician to quickly identify published studies on off-label uses and determine if a specific use is rational in a patient care scenario. References direct the reader to the full literature for more comprehensive information before patient care decisions are made. Direct questions or comments regarding Off-Label Drug Uses to jgeneral@kumc.edu .
Impact of i-STAT Point of Care Implementation in a Pharmacist-Managed Anticoagulation Clinic: A Retrospective Analysis
Authors: Challen Laura Moretti , Nguyen Tuong-Giao , Villalon Aimee
Published: February 2011

Purpose

To evaluate the impact that close monitoring by a clinical pharmacist using the i-STAT point of care (POC) machine had on outcomes of anticoagulation patients.

Methods

This study was a retrospective chart review of 40 patients with an average age of 58.7 who served as their own historical control. Data collected included international normalized ratio (INR) results, indication for warfarin, adverse drug events, emergency room visits, and hospitalizations both before and after the i-STAT POC implementation (November 2006 to August 2009).

Results

The proportion of time within therapeutic INR range 2.0 to 3.0 was higher after i-STAT POC implementation compared to before (46.3% and 56.2%; P = .001). When a wider INR range was analyzed (1.8-3.2), the proportion of time within range was 64.6% versus 68.9% ( P = .001). In terms of safety, 27 adverse events were documented before and 22 adverse events were documented after i-STAT implementation. Eighteen hospitalizations were related to bleeding or clotting and were distributed evenly between before and after i-STAT implementation. Percentages of medication nonadherence were 12.5% before and 12.1% after the implementation.

Conclusion

The results of this study indicate that implementation of the i-STAT POC machine in a pharmacist-managed anticoagulation clinic increased percent of time within therapeutic INR by 9.9%. Patient INR results were better controlled at more stable levels. Furthermore, use of i-STAT POC showed improvement in terms of safety, adherence, and cost. Though the significance of these results requires further study, the promising positive outcomes will certainly encourage implementation of this model on a larger scale.