bluuebunny/crossref_metadata_2025 huggingface dataset:
Testing an Inpatient Nursing Intensity Billing Model
Authors: Welton John M. , Dismuke Clara E.
Published: July 2008

There has been growing concern about the costs and intensity of inpatient nursing care, which consumes more than 40% of hospital direct costs and $165 billion each year. Allocating nursing labor as an average cost per patient and charged as room and board creates cost compression, distorts hospital payment, and hides the economic value of nurses. This article examines a method for adjusting daily room charges using nursing intensity weights assigned by the diagnosis related group. In a test using claims data from 286 hospitals in four states representing 1,856,256 patient discharges in 2002, the nursing intensity adjustment improved explained total cost variance by 8.5% for adult all payer patients ( R2 = .4448 vs. .4825) and 9.4% for Medicare only patients ( R2 = .4387 vs. .4798) compared to unadjusted days. This article discusses unbundling inpatient nursing care intensity and charges from room and board and recommends implementing this billing process at all U.S. hospitals.
Religious Involvement and Prostate Cancer Screening Behaviors Among Southeastern African American Men
Authors: Holt Cheryl L. , Wynn Theresa A. , Darrington Jasmine
Published: July 2008

This study examined the relationship between religious involvement and prostate cancer screening behavior among a probability sample of 199 African American men. Religious involvement was assessed by telephone via a multidimensional instrument. Engaging in religious behaviors was predictive of reporting a digital rectal examination (DRE) within the past year. Religious beliefs and behaviors were predictive of behavioral intention for DRE in the next 6 months. Religious behaviors were predictive of reporting an appointment for a DRE in the next 6 months. All analyses were controlled for age, education, and marital status. None of the predictions were significant for prostate-specific antigen testing. Understanding the role of religious involvement in cancer beliefs and screening is important. Such knowledge can inform educational interventions for this group, which is disproportionately affected by prostate cancer.
Sex and Drugs: High-Risk Behaviors at Circuit Parties
Authors: Weidel James John , Provencio-Vasquez Elias , Grossman Janet
Published: July 2008

HIV and other sexually transmitted infection rates are increasing among men who have sex with men. This increase may be attributed to the high rates of drug use and risky sexual behaviors at gay festive events called circuit parties. Although few studies have examined the actual level of risk, the implications from the available studies underscore the need for the development of interventions to address this public health concern. The 5 As approach provides an evidence-based approach to assist in behavior change that may reduce the HIV and sexually transmitted infection rates among gay and bisexual men who attend circuit parties. This article reviews the findings and recommendations from the few available studies on circuit parties and risk behavior. The authors propose that the 5 As approach for behavioral change be adapted by practitioners in the primary care setting.
Review: Efficacy and safety of adalimumab in Crohn's disease
Authors: Lichtenstein Gary R. , Panaccione Remo , Mallarkey Gordon
Published: July 2008

Adalimumab (ADA) is a subcutaneously (SC) self-administered fully human Ig G1 monoclonal antibody directed against tumor necrosis factor alpha (TNFα). In the CLASSIC I dose-ranging trial, ADA was superior to placebo for inducing remission in patients with moderate-to-severe Crohn's disease (CD) naive to TNFα inhibitor therapy. In CLASSIC II, patients in remission following CLASSIC I maintained remission for up to 56 weeks while on ADA. In CHARM, approximately 40% of the 499 patients with moderate-to-severe CD who responded to ADA, maintained remission at 26 and 52 weeks, thus confirming long-term efficacy. ADA demonstrated steroid-sparing properties, beneficial effects in patients with perianal fistulas, and decreases in rates of hospitalization and surgery. Sub-group analyses demonstrated similar remission rates irrespective of concomitant immunosuppressive use or previous exposure to other TNFα inhibitor therapy. In the GAIN trial, 325 patients who had either lost response or become intolerant to infliximab (IFX) were randomized to recieve ADA induction therapy or placebo. In this difficult-to-treat patient population, 21% achieved remission and half demonstrated clinical benefit from ADA induction therapy. Injection site reactions may occur with SC ADA (2—5% of patients), which are generally less dramatic in nature than infusion reactions experienced with intravenous IFX. Immunogenicity occurs with all monoclonal antibodies; however, in the CD development program anti-ADA antibodies were detected at low rates (0.7 and 2.6% of patients in the CLASSIC I and CLASSIC II studies, respectively). Based on robust short- and long-term efficacy data from large randomized controlled trials and a favorable safety signal, ADA has become a key addition to the therapeutic armamentarium in the treatment of moderate-to-severe CD.
Review: Chemoprevention of esophageal adenocarcinoma
Authors: Abrams Julian A.
Published: July 2008

The incidence of esophageal adenocarcinoma (EAC) is rising rapidly in Western countries, and effective chemoprevention for this malignancy is lacking. Endoscopic surveillance of patients with Barrett's esophagus is currently employed to diagnose EAC at earlier stages, but this strategy has several limitations. Non-steroidal anti-inflammatory drugs and proton pump inhibitors are the most promising agents for prevention of EAC, and a randomized controlled trial of aspirin and esomeprazole is ongoing. Other agents under investigation include green tea, berries, and antioxidants. Cost-effectiveness analyses have shown that chemopreventive agents need to be highly effective at preventing EAC in order to have benefit beyond endoscopic surveillance.
Review: Enteroendocrine cells: Neglected players in gastrointestinal disorders?
Authors: Moran Gordon W. , Leslie Fiona C. , Levison Scott E. , McLaughlin John T.
Published: July 2008

Enteroendocrine cells (EEC) form the basis of the largest endocrine system in the body. They secrete multiple regulatory molecules which control physiological and homeostatic functions, particularly postprandial secretion and motility. Their key purpose is to act as sensors of luminal contents, either in a classical endocrine fashion, or by a paracrine effect on proximate cells, notably vagal afferent fibres. They also play a pivotal role in the control of food intake, and emerging data add roles in mucosal immunity and repair. We propose that EEC are fundamental in several gastrointestinal pathologies, notably Post-infectious Irritable Bowel Syndrome, infectious enteritis, and possibly inflammatory bowel disease. Further work is needed to fully illustrate the importance, detailed biology and therapeutic potential of these frequently overlooked cells.
Review: Current status of antiviral therapy for hepatitis B
Authors: Lau Daryl T.-Y. , Bleibel Wissam
Published: July 2008

Chronic hepatitis B (CHB) is a major public health problem affecting up to 400 million people globally. Complications of CHB including liver failure and hepatocellular carcinoma result in 1.2 million deaths per year, making CHB the 10th leading cause of mortality worldwide. The natural history of CHB is variable and complex. The past decade witnessed important developments for the therapy of hepatitis B and marked the new era of oral therapy. The ultimate goal of CHB therapy is to arrest the progression of liver injury and to prevent the development of liver failure and hepatocellular carcinoma. Currently, six agents are approved for the treatment of CHB. Each of these agents, given as monotherapy, has been shown to produce virological, biochemical, and histological benefits for both HBeAg positive and negative CHB. There are, however, limitations in spite of their efficacy. The significant side-effect profile of interferon, for example, limits its long-term use. The approved oral agents are tolerable with prolonged use but drug resistance could limit long-term monotherapy. To date, combination therapy with nucleoside analogue and pegylated interferon or two nucleos(t)ide analogues given for one year does not show superiority in durability of response compared to monotherapy. Ongoing research effort is critical to identify the ideal hepatitis B therapy that is safe, effective, and produces durable response with a finite course of therapy. It is equally important to conduct a well designed, prospective natural history study to identify predictors of disease progression. This will accurately guide treatment strategy for this important disease.
Review: Innovative monoclonal antibody therapies in multiple sclerosis
Authors: Linker Ralf A. , Kieseier Bernd C.
Published: July 2008

The recent years have witnessed great efforts in establishing new therapeutic options for multiple sclerosis (MS), especially for relapsing—remitting disease courses. In particular, the application of monoclonal antibodies provide innovative approaches allowing for blocking or depleting specific molecular targets, which are of interest in the pathogenesis of MS. While natalizumab received approval by the US Food and Drug Administration and the European Medicines Agency in 2006 as the first monoclonal antibody in MS therapy, rituximab, alemtuzumab, and daclizumab were successfully tested for relapsing-remitting MS in small cohorts in the meantime. Here, we review the data available from these recent phase II trials and at the same time critically discuss possible pitfalls which may be relevant for clinical practice. The results of these studies may not only broaden our therapeutic options in the near future, but also provide new insights into disease pathogenesis.
Review: Treatment of neuromyelitis optica: Current debate
Authors: Okamoto Tomoko , Ogawa Masafumi , Youwei Lin  , Murata Miho , Miyake Sachiko , Yamamura Takashi
Published: July 2008

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that largely affects optic nerves and spinal cord. Recent studies have identified an elevation of serum anti-aquaporin 4 antibody as a hallmark of NMO. Typical cases of NMO significantly differ from multiple sclerosis (MS) in immunological markers, histopathology, and responses to therapy. In fact, plasma exchange may be more efficacious for NMO than MS, whereas interferon-β is recommended for MS but not for NMO. An emerging idea that pathogenesis of NMO may involve an interaction of the newly identified helper T cell subset, Th17, with B cells offers potential targets of therapy.
Review: Is levetiracetam different from other antiepileptic drugs? Levetiracetam and its cellular mechanism of action in epilepsy revisited
Authors: Surges Rainer , Volynski Kirill E. , Walker Matthew C.
Published: July 2008

Levetiracetam (LEV) is a new antiepileptic drug that is clinically effective in generalized and partial epilepsy syndromes as sole or add-on medication. Nevertheless, its underlying mechanism of action is poorly understood. It has a unique preclinical profile; unlike other antiepileptic drugs (AEDs), it modulates seizure-activity in animal models of chronic epilepsy with no effect in most animal models of acute seizures. Yet it is effective in acute in-vitro `seizure' models. A possible explanation for these dichotomous findings is that LEV has different mechanisms of actions, whether given acutely or chronically and in `epileptic' and control tissue. Here we review the general mechanism of action of AEDs, give an updated and critical overview about the experimental findings of LEV's cellular targets (in particular the synaptic vesicular protein SV2A) and ask whether LEV represents a new class of AED.
Human natural killer cells
Authors: Caligiuri Michael A.
Published: July 2008

Natural killer (NK) cells were discovered more than 30 years ago. NK cells are large granular lymphocytes that belong to the innate immune system because unlike T or B lymphocytes of the adaptive or antigen-specific immune system, NK cells do not rearrange T-cell receptor or immunoglobulin genes from their germline configuration. During the past 2 decades there has been a substantial gain in our understanding of what and how NK-cells “see,” lending important insights into their functions and purpose in normal immune surveillance. The most recent discoveries in NK-cell receptor biology have fueled translational research that has led to remarkable results in treating human malignancy.
Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera
Authors: Kiladjian Jean-Jacques , Cassinat Bruno , Chevret Sylvie , Turlure Pascal , Cambier Nathalie , Roussel Murielle , Bellucci Sylvia , Grandchamp Bernard , Chomienne Christine , Fenaux Pierre
Published: July 2008

Interferon-α (IFN-α) is a nonleukemogenic treatment of polycythemia vera (PV) able to induce cytogenetic remissions. Its use is limited by toxicity, leading to treatment discontinuation in approximately 20% of patients. We completed a phase 2 multicenter study of pegylated IFN-α-2a in 40 PV patients. Objectives included evaluation of efficacy, safety, and monitoring of residual disease using JAK2V617F quantification (%V617F). Median follow-up was 31.4 months. At 12 months, all 37 evaluable patients had hematologic response, including 94.6% complete responses (CRs). Only 3 patients (8%) had stopped treatment. After the first year, 35 patients remained in hematologic CR, including 5 who had stopped pegylated IFN-α-2a. Sequential samples for %V617F monitoring, available in 29 patients, showed %V617F decrease in 26 (89.6%). Median %V617F decreased from 45% before pegylated IFN-α-2a to 22.5%, 17.5%, 5%, and 3% after 12, 18, 24, and 36 months, respectively. Molecular CR (JAK2V617F undetectable) was achieved in 7 patients, lasting from 6+ to 18+ months, and persisted after pegylated IFN-α-2a discontinuation in 5. No vascular event was recorded. These results show that pegylated IFN-α-2a yields high rates of hematologic and molecular response in PV with limited toxicity, and could even eliminate the JAK2 mutated clone in selected cases. Available at www.clinicaltrials.gov as #NCT00241241.
Prion diseases are efficiently transmitted by blood transfusion in sheep
Authors: Houston Fiona , McCutcheon Sandra , Goldmann Wilfred , Chong Angela , Foster James , Sisó Silvia , González Lorenzo , Jeffrey Martin , Hunter Nora
Published: July 2008

The emergence of variant Creutzfeld-Jakob disease, following on from the bovine spongiform encephalopathy (BSE) epidemic, led to concerns about the potential risk of iatrogenic transmission of disease by blood transfusion and the introduction of costly control measures to protect blood supplies. We previously reported preliminary data demonstrating the transmission of BSE and natural scrapie by blood transfusion in sheep. The final results of this experiment, reported here, give unexpectedly high transmission rates by transfusion of 36% for BSE and 43% for scrapie. A proportion of BSE-infected tranfusion recipients (3 of 8) survived for up to 7 years without showing clinical signs of disease. The majority of transmissions resulted from blood collected from donors at more than 50% of the estimated incubation period. The high transmission rates and relatively short and consistent incubation periods in clinically positive recipients suggest that infectivity titers in blood were substantial and/or that blood transfusion is an efficient method of transmission. This experiment has established the value of using sheep as a model for studying transmission of variant Creutzfeld-Jakob disease by blood products in humans.
Population-based estimate of sibling risk for preterm birth, preterm premature rupture of membranes, placental abruption and pre-eclampsia
Authors: Plunkett Jevon , Borecki Ingrid , Morgan Thomas , Stamilio David , Muglia Louis J
Published: July 2008

Background

Adverse pregnancy outcomes, such as preterm birth, preeclampsia and placental abruption, are common, with acute and long-term complications for both the mother and infant. Etiologies underlying such adverse outcomes are not well understood. As maternal and fetal genetic factors may influence these outcomes, we estimated the magnitude of familial aggregation as one index of possible heritable contributions.

Using the Missouri Department of Health's maternally-linked birth certificate database, we performed a retrospective population-based cohort study of births (1989–1997), designating an individual born from an affected pregnancy as the proband for each outcome studied. We estimated the increased risk to siblings compared to the population risk, using the sibling risk ratio, λs, and sibling-sibling odds ratio (sib-sib OR), for the adverse pregnancy outcomes of preterm birth, preterm premature rupture of membranes (PPROM), placental abruption, and pre-eclampsia.

Results

Risk to siblings of an affected individual was elevated above the population prevalence of a given disorder, as indicated by λS (λS (95% CI): 4.3 (4.0–4.6), 8.2 (6.5–9.9), 4.0 (2.6–5.3), and 4.5 (4.4–4.8), for preterm birth, PPROM, placental abruption, and pre-eclampsia, respectively). Risk to siblings of an affected individual was similarly elevated above that of siblings of unaffected individuals, as indicated by the sib-sib OR (sib-sib OR adjusted for known risk factors (95% CI): 4.2 (3.9–4.5), 9.6 (7.6–12.2), 3.8 (2.6–5.5), 8.1 (7.5–8.8) for preterm birth, PPROM, placental abruption, and pre-eclampsia, respectively).

Conclusion

These results suggest that the adverse pregnancy outcomes of preterm birth, PPROM, placental abruption, and pre-eclampsia aggregate in families, which may be explained in part by genetics.
WildSilkbase: An EST database of wild silkmoths
Authors: Arunkumar KP , Tomar Archana , Daimon Takaaki , Shimada Toru , Nagaraju J
Published: July 2008

Background

Functional genomics has particular promise in silkworm biology for identifying genes involved in a variety of biological functions that include: synthesis and secretion of silk, sex determination pathways, insect-pathogen interactions, chorionogenesis, molecular clocks. Wild silkmoths have hardly been the subject of detailed scientific investigations, owing largely to non-availability of molecular and genetic data on these species. As a first step, in the present study we generated large scale expressed sequence tags (EST) in three economically important species of wild silkmoths. In order to make these resources available for the use of global scientific community, an EST database called 'WildSilkbase' was developed.

Description

WildSilkbase is a catalogue of ESTs generated from several tissues at different developmental stages of 3 economically important saturniid silkmoths, an Indian golden silkmoth, Antheraea assama, an Indian tropical tasar silkmoth, A. mylitta and eri silkmoth, Samia cynthia ricini. Currently the database is provided with 57,113 ESTs which are clustered and assembled into 4,019 contigs and 10,019 singletons. Data can be browsed and downloaded using a standard web browser. Users can search the database either by BLAST query, keywords or Gene Ontology query. There are options to carry out searches for species, tissue and developmental stage specific ESTs in BLAST page. Other features of the WildSilkbase include cSNP discovery, GO viewer, homologue finder, SSR finder and links to all other related databases. The WildSilkbase is freely available from http://www.cdfd.org.in/wildsilkbase/.

Conclusion

A total of 14,038 putative unigenes was identified in 3 species of wild silkmoths. These genes provide important resources to gain insight into the functional and evolutionary study of wild silkmoths. We believe that WildSilkbase will be extremely useful for all those researchers working in the areas of comparative genomics, functional genomics and molecular evolution in general, and gene discovery, gene organization, transposable elements and genome variability of insect species in particular.
Laminin enhances the growth of human neural stem cells in defined culture media
Authors: Hall Peter E , Lathia Justin D , Caldwell Maeve A , ffrench-Constant Charles
Published: July 2008

Background

Human neural stem cells (hNSC) have the potential to provide novel cell-based therapies for neurodegenerative conditions such as multiple sclerosis and Parkinson's disease. In order to realise this goal, protocols need to be developed that allow for large quantities of hNSC to be cultured efficiently. As such, it is important to identify factors which enhance the growth of hNSC. In vivo, stem cells reside in distinct microenvironments or niches that are responsible for the maintenance of stem cell populations. A common feature of niches is the presence of the extracellular matrix molecule, laminin. Therefore, this study investigated the effect of exogenous laminin on hNSC growth.

Results

To measure hNSC growth, we established culture conditions using B27-supplemented medium that enable neurospheres to grow from human neural cells plated at clonal densities. Limiting dilution assays confirmed that neurospheres were derived from single cells at these densities. Laminin was found to increase hNSC numbers as measured by this neurosphere formation. The effect of laminin was to augment the proliferation/survival of the hNSC, rather than promoting the undifferentiated state. In agreement, apoptosis was reduced in dissociated neurospheres by laminin in an integrin β1-dependent manner.

Conclusion

The addition of laminin to the culture medium enhances the growth of hNSC, and may therefore aid their large-scale production.
Podocyte specific knock out of selenoproteins does not enhance nephropathy in streptozotocin diabetic C57BL/6 mice
Authors: Blauwkamp Marsha N , Yu Jingcheng , Schin MaryLee A , Burke Kathleen A , Berry Marla J , Carlson Bradley A , Brosius Frank C , Koenig Ronald J
Published: July 2008

Background

Selenoproteins contain selenocysteine (Sec), commonly considered the 21st genetically encoded amino acid. Many selenoproteins, such as the glutathione peroxidases and thioredoxin reductases, protect cells against oxidative stress by functioning as antioxidants and/or through their roles in the maintenance of intracellular redox balance. Since oxidative stress has been implicated in the pathogenesis of diabetic nephropathy, we hypothesized that selenoproteins protect against this complication of diabetes.

Methods

C57BL/6 mice that have a podocyte-specific inability to incorporate Sec into proteins (denoted in this paper as PodoTrsp-/-) and control mice were made diabetic by intraperitoneal injection of streptozotocin, or were injected with vehicle. Blood glucose, body weight, microalbuminuria, glomerular mesangial matrix expansion, and immunohistochemical markers of oxidative stress were assessed.

Results

After 3 and 6 months of diabetes, control and PodoTrsp-/- mice had similar levels of blood glucose. There were no differences in urinary albumin/creatinine ratios. Periodic acid-Schiff staining to examine mesangial matrix expansion also demonstrated no difference between control and PodoTrsp-/- mice after 6 months of diabetes, and there were no differences in immunohistochemical stainings for nitrotyrosine or NAD(P)H dehydrogenase, quinone 1.

Conclusion

Loss of podocyte selenoproteins in streptozotocin diabetic C57BL/6 mice does not lead to increased oxidative stress as assessed by nitrotyrosine and NAD(P)H dehydrogenase, quinone 1 immunostaining, nor does it lead to worsening nephropathy.
Development and evaluation of a cancer-related fatigue patient education program: protocol of a randomized controlled trial
Authors: Stuhldreher Nina , Reif Karl , de Vries Ulrike , Görres Stefan , Petermann Franz
Published: July 2008

Background

Cancer-related fatigue (CRF) and its impact on patients' quality of life has been an increasing subject of research. However, in Germany there is a lack of evidence-based interventions consistent with the multidimensional character of fatigue. The objective of this study is to develop and evaluate a self-management program for disease-free cancer patients to cope with CRF.

Methods

Based on evidence extracted from a literature review, a curriculum for the self-management program was elaborated. The curriculum was reviewed and validated by an interdisciplinary expert group and the training-modules will be pretested with a small number of participants and discussed in terms of feasibility and acceptance.

To determine the efficacy of the program a randomised controlled trial will be carried out: 300 patients will be recruited from oncological practices in Bremen, Germany, and will be allocated to intervention or control group. The intervention group participates in the program, whereas the control group receives standard care and the opportunity to take part in the program after the end of the follow-up (waiting control group). Primary outcome measure is the level of fatigue, secondary outcome measures are quality of life, depression, anxiety, self-efficacy and physical activity. Data will be collected before randomisation, after intervention, and after a follow-up of 6 months.

Discussion

Because there are no comparable self-management programs for cancer survivors with fatigue, the development of the curriculum has been complex; therefore, the critical appraisal by the experts was an important step to validate the program and their contributions have been integrated into the curriculum. The experts appreciated the program as filling a gap in outpatient cancer care.

If the results of the evaluation prove to be satisfactory, the outpatient care of cancer patients can be broadened and supplemented.

Trial Registration

ClinicalTrials NCT00552552
A Genome-Wide Linkage Scan for Age at Menarche in Three Populations of European Descent
Authors: Anderson Carl A. , Zhu Gu , Falchi Mario , van den Berg Stéphanie M. , Treloar Susan A. , Spector Timothy D. , Martin Nicholas G. , Boomsma Dorret I. , Visscher Peter M. , Montgomery Grant W.
Published: July 2008

Context: Age at menarche (AAM) is an important trait both biologically and socially, a clearly defined event in female pubertal development, and has been associated with many clinically significant phenotypes.

Objective: The objective of the study was to identify genetic loci influencing variation in AAM in large population-based samples from three countries.

Design/Participants: Recalled AAM data were collected from 13,697 individuals and 4,899 pseudoindependent sister-pairs from three different populations (Australia, The Netherlands, and the United Kingdom) by mailed questionnaire or interview. Genome-wide variance components linkage analysis was implemented on each sample individually and in combination.

Results: The mean, sd, and heritability of AAM across the three samples was 13.1 yr, 1.5 yr, and 0.69, respectively. No loci were detected that reached genome-wide significance in the combined analysis, but a suggestive locus was detected on chromosome 12 (logarithm of the odds = 2.0). Three loci of suggestive significance were seen in the U.K. sample on chromosomes 1, 4, and 18 (logarithm of the odds = 2.4, 2.2 and 3.2, respectively).

Conclusions: There was no evidence for common highly penetrant variants influencing AAM. Linkage and association suggest that one trait locus for AAM is located on chromosome 12, but further studies are required to replicate these results.
The JNK-dependent CaMK pathway restrains the reversion of committed cells during osteoclast differentiation
Authors: Chang Eun-Ju , Ha Jeongim , Huang Hao , Kim Hyung Joon , Woo Jung Hoon , Lee Youngkyun , Lee Zang Hee , Kim Ju Han , Kim Hong-Hee
Published: July 2008

Osteoclastogenesis involves the commitment of macrophage-lineage precursors to tartrate-resistant acid phosphatase-positive (TRAP+) mononuclear pre-osteoclasts (pOCs) and subsequent fusion of pOCs to form multinuclear mature osteoclasts. Despite many studies on osteoclast differentiation, little is known about the signaling mechanisms that specifically mediate the osteoclastic commitment. In this study, we found that inhibition of JNK at the pOC stage provoked reversion of TRAP+ cells to TRAP– cells. The conversion to TRAP– cells occurred with concomitant return to the state with higher expression of macrophage antigens, and greater activity of phagocytosis and dendritic-differentiation potential. JNK inhibition at the pOC stage reduced NFATc1 and CaMK levels, and addition of active NFATc1 partially rescued the effect of JNK inhibition. In addition, the level of NFATc1 was decreased by knockdown of CaMK by RNAi and by catalytic inhibition of CaMK, which both caused the reversion of pOCs to macrophages. These data suggest that JNK activity is specifically required for maintaining the committed status during osteoclastogenesis and that the CaMK-NFATc1 pathway is the key element in that specific role of JNK.
Telescoping self-aligned metal-catalyzed carbon nanotube piezoresistors as strain gauges
Authors: Tabib-Azar M
Published: July 2008

Multiwalled carbon nanotube (MWCNT) bridges, grown using low-pressure, metal-catalyzed, chemical vapour deposition (CVD) technique between silicon posts, were used as tiny piezoresistors to monitor vibration and bending/deformation of silicon cantilever beams. The weld strength of the CNTs, measured using atomic force microscopy (AFM), was larger than 100 nN/CNT and their full-scale resistance change was larger than 105 ω. The effective longitudinal piezoresistivity of these CNTs was larger than 4×10−8 Pa−1, which is larger than that of π44 in silicon.
Non-percolating nanotube networks for thin film transistors: A pathway to channel length reduction
Authors: Tassi N G , Rabolt J F , Blanchet G B
Published: July 2008

This study outlines a method to increase the transconductance of thin film transistors (TFTs) by assembling non-percolating random arrays of carbon nanotubes. It represents an effective, simple tool to substantially reduce the transistor channel length, thus increase transconductance, without lessening the on/off ratio. When non-percolating arrays of carbon nanotubes are linked via a semiconducting overlay, the majority of current paths between source and drain follow the highly conducting nanotubes with short, switchable semiconducting links completing the circuit. This field-induced percolating network allows for high transconductance with relatively large source—drain distance. Thus, transistors can be manufactured inexpensively by commercially available techniques using a variety of available semiconductors.
Nanopatterned working electrode with carbon nanotubes improving electrochemical sensors
Authors: Prasek J , Hubalek J , Adamek M , Jasek O , Zajickova L
Published: July 2008

This paper deals with the problem of the replacement of mercury drop electrodes with solid electrodes in standard polarography. The screen-printed thick-film sensor with a three-electrode system was prepared. A working electrode was modified with nanopatterned nanostructures. Vertically aligned carbon nanotubes (CNTs) were grown on the working electrode. The process of the nanotubes growing was tested to create a homogeneous (CNTs) and high density CNT layer directly on the thick-film silver (Ag) layer. Thereby, the modified electrode is presented to be very perspective in heavy metal detection using electrochemical methods because of improvement of detection properties. The authors were able to determine the concentration of cadmium ions in units of µmol/L.
Human RNA 5′-kinase (hClp1) can function as a tRNA splicing enzyme in vivo
Authors: Ramirez Alejandro , Shuman Stewart , Schwer Beate
Published: July 2008

Yeast and human Clp1 proteins are homologous components of the mRNA 3′-cleavage-polyadenylation machinery. Recent studies highlighting an association of human Clp1 (hClp1) with tRNA splicing endonuclease and an intrinsic RNA-specific 5′-OH polynucleotide kinase activity of hClp1 have prompted speculation that Clp1 might play a catalytic role in tRNA splicing in animal cells. Here, we show that expression of hClp1 in budding yeast can complement conditional and lethal mutations in the essential 5′-OH RNA kinase module of yeast or plant tRNA ligases. The tRNA splicing activity of hClp1 in yeast is abolished by mutations in the kinase active site. In contrast, overexpression of yeast Clp1 (yClp1) cannot rescue kinase-defective tRNA ligase mutants, and, unlike hClp1, the purified recombinant yClp1 protein has no detectable RNA kinase activity in vitro. Mutations of the yClp1 ATP-binding site do not affect yeast viability. These findings, and the fact that hClp1 cannot complement growth of a yeast clp1Δ strain, indicate that yeast and human Clp1 proteins are not functional orthologs, despite their structural similarity. Although hClp1 can perform the 5′-end-healing step of a yeast-type tRNA splicing pathway in vivo, it is uncertain whether its kinase activity is necessary for tRNA splicing in human cells, given that other mammalian counterparts of yeast-type tRNA repair enzymes are nonessential in vivo.
Partial activity is seen with many substitutions of highly conserved active site residues in human Pseudouridine synthase 1
Authors: Sibert Bryan S. , Fischel-Ghodsian Nathan , Patton Jeffrey R.
Published: July 2008

Pseudouridine synthase 1 (Pus1p) is an enzyme that converts uridine to Pseudouridine (Ψ) in tRNA and other RNAs in eukaryotes. The active site of Pus1p is composed of stretches of amino acids that are highly conserved and it is hypothesized that mutation of select residues would impair the enzyme's ability to catalyze the formation of Ψ. However, most mutagenesis studies have been confined to substitution of the catalytic aspartate, which invariably results in an inactive enzyme in all Ψ synthases tested. To determine the requirements for particular amino acids at certain absolutely conserved positions in Pus1p, three residues (R116, Y173, R267) that correspond to amino acids known to compose the active site of TruA, a bacterial Ψ synthase that is homologous to Pus1p, were mutated in human Pus1p (hPus1p). The effects of those mutations were determined with three different in vitro assays of pseudouridylation and several tRNA substrates. Surprisingly, it was found that each of these components of the hPus1p active site could tolerate certain amino acid substitutions and in fact most mutants exhibited some activity. The most active mutants retained near wild-type activity at positions 27 or 28 in the substrate tRNA, but activity was greatly reduced or absent at other positions in tRNA readily modified by wild-type hPus1p.
Reaching the top of the ladder? Locating the voices of excluded young people within the participation debate
Authors: Macpherson Suzi
Published: July 2008

The social exclusion debate since it emerged in the UK in the late 1990s has focused centrally on promoting ‘participation’ in decision-making settings. While young people have been a central group of concern within this debate, there has been a broad neglect of the issues facing excluded young people in engaging in participatory settings. Drawing on data from local partnerships to promote social inclusion in Scotland, this article reflects on approaches to engage excluded young people in decision-making settings. Offering young people choice about how, when and where they engage is vital if we are to increase the opportunities for young people to influence decision making.
Addressing poverty through community-based income generation projects: the evidence from South Africa
Authors: Surender Rebecca , Niekerk Robert Van
Published: July 2008

This article presents the findings of a qualitative study of an income generation initiative developed in South Africa during the late1990s. The initiative reflected a growing policy emphasis that work had to be a main pathway out of poverty, and was designed to encourage entrepreneurship among deprived communities by providing grants for small business creation. The study found several barriers and challenges to successful implementation and policy outcomes of the initiative, including: a lack of capacity in the targeted communites; poor physical infrastructure; a lack of capacity in the implementing department; and policy confusion about the programme's objectives.
Policy making in Northern Ireland: ignoring the evidence
Authors: Knox Colin
Published: July 2008

The public policy-making process in Northern Ireland during the period of direct rule from Westminster (1972–99) was dominated by senior civil servants working for busy British ministers preoccupied with wider constitutional and security issues. The recent return to devolved government after its fitful start has ushered in a new era of policy making informed to a much greater extent by evidence gathering. This article considers a significant policy issue – the Review of Public Administration in Northern Ireland – as a means of examining how policy making is influenced by macro political factors aimed at stabilising the power-sharing Executive.
Aminoglycoside-Induced Vestibular Injury: Maintaining a Sense of Balance
Authors: Ariano Robert E , Zelenitsky Sheryl A , Kassum Diamond A
Published: July 2008

Objective

To describe the mechanism and risk factors for the development of aminoglycoside-induced vestibular injury and discuss their implications for therapeutic monitoring of aminoglycoside antibiotics.

Data Sources:

A MEDLINE search (1975–January 2008) was performed to identify literature on aminoglycoside-induced vestibular injury and risk factors associated with this outcome and their impact on therapeutic drug monitoring. Additional references were identified through review of bibliographies of identified articles.

Study Selection And Data Extraction:

Data on the mechanisms of vestibular toxicity and its development in association with aminoglycoside exposure were extracted from identified references.

Data Synthesis:

The mechanism leading to the development of irreversible vestibular injury from exposure to aminoglycosides appears to be through the excessive production of oxidative free radicals. This production and subsequent toxicity appears to be a time-dependent process and is unrelated to dose or serum concentration. For similarly designed studies, the pooled incidence of vestibular toxicity is 10.9% for gentamicin, 7.4% for amikacin, 3.5% for tobramycin, and 1.1% for netilmicin. Current evidence suggests that this form of drug toxicity is not restricted to traditionally dosed systemic therapy, since intraperitoneal administration, high-dose once-daily administration, topical inhalation, and eardrop administration have all been associated with the development of this adverse outcome.

Conclusions:

Given the lack of association between serum concentrations and vestibulotoxicity, it is imperative for the pharmacist to interview the patient and not focus solely on maintaining target range drug concentrations. Minimizing the duration of exposure to aminoglycosides is recommended to reduce the risk from this form of drug toxicity.
Formulary Forum: Ixabepilone: A New Antimitotic for the Treatment of Metastatic Breast Cancer
Authors: Bhushan Shriya , Walko Christine M
Published: July 2008

Objective:

To evaluate the safety and efficacy of ixabepilone as a new antimitotic chemotherapeutic agent for the treatment of breast cancer.

Data Sources:

Data were identified by searches of MEDLINE, PubMed, and American Society of Clinical Oncology abstracts from 1966 to March 2008, using the primary search terms ixabepilone, epothilones, BMS-247550, and breast cancer.

Study Selection And Data Extraction:

Phase 1, Phase 2, and Phase 3 clinical trials examining the safely and efficacy of ixabepilone and its place in cancer treatment were reviewed. Preference was given to large Phase 2 and 3 clinical trials in the breast cancer population. Manufacturer product information was used to supplement data lacking in published trials.

Data Synthesis:

Ixabepilone belongs to a novel class of drugs, the epothilones, which are nontaxano microtubule-stabilizing agents. Ixabepilone, in combination with capecitabine, has been approved by the Food and Drug Administration for treatment in patients with metastatic or locally advanced breast cancer that progresses after anthracycline and taxane therapy, or in patients with taxane-resistant cancer with contraindication to further anthracycline therapy. Ixabepilone has also been approved as monotherapy in patients with metastatic and locally advanced breast cancer refractory to taxanes, anthracyclines, and capecitabine. The most common adverse reactions reported by 20% or more of the patients receiving ixabepilone were peripheral sensory neuropathy, fatigue/asthenia, myalgia/arthralgia, alopecia, nausea, vomiting, stomatitis/mucositis, diarrhea, and musculoskeletal pain. The most common hematologic abnormalities seen in more than 40% of the patients include neutropenia, leukopenia, anemia, and thrombocytopenia. Premedication with histamine H1 and H2 antagonists is recommended to prevent hypersensitivity reactions.

Conclusions:

Based on the clinical trials reviewed here and the current information available, ixabepilone is a welcome addition to the options available for the treatment of patients with metastatic breast cancer refractory to standard therapy.
Impact of Health Literacy on Health Outcomes in Ambulatory Care Patients: A Systematic Review
Authors: Keller Darcie L , Wright Julie , Pace Heather A
Published: July 2008

Objective

To examine the relationship between low health literacy and disease state control and between low health literacy medication adherence in the primary caro setting.

Data Sources:

The following databases were searched for relevant articles from date of inception to April 2008: The Cochrane Database of Systematic Reviews, Cumulative Index to Nursing & Allied Health Literature, EMBASE, Education Resources Information Center, PsyclNFO, International Pharmaceutical Abstracts, and Iowa Drug Information Service. MEDLINE was searched from 1966 to April 2008. Key words included literacy, health literacy, health education, educational status, disease outcomes, health outcomes, adherence, medication adherence, and patient compliance. Additional articles were identified by reviewing reference sections of retrieved articles.

Study Selection And Data Extraction:

Studies using a validated measure of health literacy and performing statistical analysis to evaluate the relationship between health literacy and disease state control or medication adherence were evaluated.

Data Synthesis:

Eleven evaluations, including 10 discrete studies, met eligibility criteria. Six studies evaluated the relationship between health literacy and disease state control, 3 evaluated health literacy and medication adherence, and 1 study evaluated health literacy and both outcomes. A quality rating of poor, fair, or good was assigned to each study based on the study question, population, outcome measures, statistical analysis, and results. Eight studies had good quality, 1 was fair, and 2 were poor. Two high-quality studies demonstrated statistically significant relationships with health literacy, 1 with disease state control and 1 with medication adherence. Limitations of the other studies included inadequate sample size, underrepresentation of patients with low health literacy, use of less objective outcome measures, and insufficient statistical analysis.

Conclusions:

There may be a relationship between health literacy and disease state control and health literacy and medication adherence. Future research, with adequate representation of patients with low health literacy, is needed to further define this relationship and explore interventions to overcome the impact that low health literacy may have on patient outcomes.
Trends in Statin Use and Low-Density Lipoprotein Cholesterol Levels Among US Adults: Impact of the 2001 National Cholesterol Education Program Guidelines
Authors: Mann Devin , Reynolds Kristi , Smith Donald , Muntner Paul
Published: July 2008

Background

Few data are available on the use of statins after publication of the National Cholesterol Education Program Third Adult Treatment Panel (ATP-III) guidelines in 2001.

Objective

To determine changes in statin use and its Impact on low-density lipoprotein cholesterol (LDL-C) control among US adults from 1999 to 2004.

Methods

High LDL-C levels and statin use among 1911 participants of the National Health and Nutrition Examination Survey (NHANES) 2003–2004 were determined and compared with 1770 and 2094 participants of NHANES 1999–2000 and NHANES 2001–2002, respectively. Statin use was obtained from review of participants’ drug containers. High LDL-C levels and LDL-C control were defined, using risk-specific cut-points from the ATP-III guidelines.

Results:

Statins were taken by 24 million Americans in 2003–2004, an increase from 12.5 million in 1999–2000. In 1999–2000, 2001–2002, and 2003–2004, statins were being used by 19.6%, 27.3%, and 35.9% of US adults with high LDL-C levels, respectively (p trend <0.001). Age-standardized mean LDL-C declined from 119.9 to 112.0 to 100.7 mg/dL among statin users between 1999–2000, 2001–2002, and 2003–2004. LDL-C control to ATP-III recommended targets was achieved by 49.7%, 67.4%, and 77.6% of statin users in 1999–2000, 2001–2002, and 2003–2004, respectively (p trend <0.001). Among US adults with high LDL-C, after multivariate adjustment, non-Hispanic blacks were 39% less likely (prevalence ratio = 0.61; 95 CI 0.39 to 0.97) than non-Hispanic whites to be taking statins.

Conclusions:

Statin use continues to increase among US adults and this has led to substantial improvements in LDL-C control. Nevertheless, suboptimal statin use, especially among racial/ethnic minorities, continues to prevent the maximal public health benefit from this effective drug class.
Cephalosporin-Induced Leukopenia Following Rechallenge with Cefoxitin
Authors: Whitman Craig B , Joseph Jomy M , Sjoholm Lars O
Published: July 2008

Objective

To describe a case of cefazolin-induced leukopenia in a critically ill patient who developed this adverse reaction upon rechallenge with cefoxitin.

Case Summary:

A 22-year-old male was admitted after a motor vehicle crash. β-Lactam therapy was initiated with vancomycin, cefepime, and metronidazole and, upon identification of methicillin-sensitive Staphylococcus aureus bacteremia 4 days later, therapy was narrowed to cefazolin 1 g every 12 hours. The dose was adjusted to 1 g every 12 hours during continuous venovenous hemodialysis. Imipenem was given for 2 days, resulting in a total of 18 days of β-lactam treatment, at which time he developed significant leukopenia (white blood celt [WBC] count 0.9 × 103/μL). Antimicrobial treatment was changed to tigecycline and continued for suspected pleural space infection. The patient's WBC count recovered within 4 days after the change in therapy. He was taken to surgery 8 days after cefazolin was discontinued and received perioperative prophylaxis with cefoxitin (total dose 3 g). Subsequently, the patient again became severely leukopenic (WBC count 2.4 × 103/μL). Within a week after surgery, the patient developed septic shock secondary to multidrug-resistant Escherichia coli bacteremia and died.

Discussion:

β-Lactam–induced leukopenia is a rare but well-described adverse drug reaction. It is a cumulative dose-dependent phenomenon reported to occur most often after 2 weeks of therapy. The mechanism of leukopenia is thought to be secondary to either an immune-mediated response or direct bone marrow toxicity. Rechallenge with a different β-lactam antibiotic has not been shown to consistently cause recurrent leukopenia. The case described here suggests an immune-related mechanism for the development of leukopenia. Use of the Naranjo probability scale determined the association between cephalosporin use and leukopenia to be probable.

Conclusions:

Cefazolin was a probable cause of this patient's leukopenia. It is important for clinicians to recognize β-lactam–induced leukopenia and maybe recommend use of a drug from a different antibiotic class if continued treatment is indicated.