bluuebunny/crossref_metadata_2025 huggingface dataset:
Absence of PmrAB-Mediated Phosphoethanolamine Modifications of Citrobacter rodentium Lipopolysaccharide Affects Outer Membrane Integrity
Authors: Viau Charles , Le Sage Valerie , Ting Daniel K. , Gross Jeremy , Le Moual Hervé
Published: March 2011

The PmrAB two-component system of enterobacteria regulates a number of genes whose protein products modify lipopolysaccharide (LPS). The LPS is modified during transport to the bacterial outer membrane (OM). A subset of PmrAB-mediated LPS modifications consists of the addition of phosphoethanolamine (pEtN) to lipid A by PmrC and to the core by CptA. In
Salmonella enterica
, pEtN modifications have been associated with resistance to polymyxin B and to excess iron. To investigate putative functions of pEtN modifications in
Citrobacter rodentium
, Δ
pmrAB
, Δ
pmrC
, Δ
cptA
, and Δ
pmrC
Δ
cptA
deletion mutants were constructed. Compared to the wild type, most mutant strains were found to be more susceptible to antibiotics that must diffuse across the LPS layer of the OM. All mutant strains also showed increased influx rates of ethidium dye across their OM, suggesting that PmrAB-regulated pEtN modifications affect OM permeability. This was confirmed by increased partitioning of the fluorescent dye 1-
N
-phenylnaphthylamine (NPN) into the OM phospholipid layer of the mutant strains. In addition, substantial release of periplasmic β-lactamase was observed for the Δ
pmrAB
and Δ
pmrC
Δ
cptA
strains, indicating a loss of OM integrity. This study attributes a new role for PmrAB-mediated pEtN LPS modifications in the maintenance of
C. rodentium
OM integrity.
Promoting tobacco cessation via the workplace: opportunities for improvement: Table 1
Authors: Hughes M Courtney , Yette Emily M , Hannon Peggy A , Harris Jeffrey R , Tran Nguyet M , Reid Terry R
Published: March 2011

Introduction

Little research exists on the prevalence of evidence-based tobacco cessation practices in workplaces, employer promotion of state-sponsored quitlines and predictors of these practices.

Methods

Cross-sectional analysis of the 2008 Healthy Worksite Survey, a telephone survey administered to Washington employers with 50 or more employees (n=693). The objectives were to describe workplaces' implementation of evidence-based tobacco cessation practices and identify key predictors of implementation in order to highlight opportunities for interventions.

Results

Among these employers, 38.6% promoted quitting tobacco, and 33.8% offered insurance coverage for cessation medications and counselling, 27.5% referred no-smoking violators to cessation services, and 5.7% included the state-sponsored quitline in health promotion messages. Larger workplaces and workplaces with a wellness staff, committee or coordinator had greater insurance coverage for tobacco cessation, communications promoting tobacco cessation, and promotion of the state-sponsored quitline (p<0.01). Workplaces with a wellness staff, committee or coordinator referred more violators of no-smoking policies to cessation services (p<0.01).

Conclusions

In Washington State workplaces do little to promote tobacco cessation by their employees. The lack of tobacco cessation promoting practices at small businesses, restaurants and bars, and businesses without wellness personnel indicates an opportunity for finding and reaching current smokers at businesses with limited resources. By adopting inexpensive prevention efforts, such as promoting the state-sponsored tobacco cessation quitline, employers can help employees quit smoking and, thereby, assist in improving employee health and lower medical costs.
Retrospective study of scintigraphic and radiological findings in 21 cases of enostosis‐like lesions in horses
Authors: O'Neill H. D. , Bladon B. M.
Published: March 2011

Records of horses admitted to a veterinary surgery in the UK for lameness investigation during 2000 to 2008 were reviewed. Twenty‐one horses were identified with both scintigraphic and radiological evidence of enostosis‐like lesions (ELLs), in which 68 individual foci of increased radiopharmaceutical uptake were confirmed in 57 long bones. The presenting lameness was attributed to ELLs in 15 of 21 (71 per cent) horses; the remainder were thought to be incidental findings. Five horses were subjected to a repeat examination, four of which showed the occurrence of new lesions in the same or different limbs. Hindlimbs had significantly more lesions than forelimbs, but there was no difference between the right and left limbs. All 18 horses for which follow‐up information was available were treated conservatively and returned to soundness after a variable period of time. Following ELL resolution, thoroughbred horses performed at a similar level to that before investigation and diagnosis.
Effects of lower-leg rhythmic cuff inflation on cardiovascular autonomic responses during quiet standing in healthy subjects
Authors: Niizeki Kyuichi , Tominaga Takanori , Saitoh Tadashi , Nishidate Izumi , Takahashi Tatsuhisa , Uchida Katsuo
Published: March 2011

To determine the effects of muscle pump function on cardiac autonomic activity in response to quiet standing, we simulated the muscle pump effect by rhythmic lower-leg cuff inflation (RCI) with four cuff pressures of 0 (sham), 40, 80, and 120 mmHg at 5 cycles/min. The R-R interval (RRI) and beat-to-beat blood pressure (BP) were acquired in healthy subjects (6 males and 5 females, aged 21–24 yr). From the continuous BP measurement, stroke volume (SV) was calculated by a pulse-contour method. Using spectral and cross-spectral analysis, RRI and systolic BP variability as well as the gain of spontaneous cardiac baroreflex sensitivity (sBRS) were estimated for the low- and high-frequency (HF) bands. Compared with the sham condition, RCI with cuff pressures of 80 and 120 mmHg led to increases in the mean RRI ( P < 0.01) and HF power of RRI fluctuation ( P < 0.05 for 80 mmHg and P < 0.01 for 120 mmHg) during quiet standing. Reduction in SV during standing was suppressed, and the sBRS of the HF band for standing were increased by RCI for either cuff pressure ( P < 0.05 for 80 mmHg and P < 0.01 for 120 mmHg). However, at 40 mmHg RCI, these remained unchanged. These results suggest that, during standing, RCI of the lower leg increases cardiac vagal outflow when the cuff pressure is raised enough to oppose the hydrostatic-induced venous pressure in the calf.
Depletion of tissue plasminogen activator attenuates lung ischemia-reperfusion injury via inhibition of neutrophil extravasation
Authors: Zhao Yunge , Sharma Ashish K. , LaPar Damien J. , Kron Irving L. , Ailawadi Gorav , Liu Yuan , Jones David R. , Laubach Victor E. , Lau Christine L.
Published: March 2011

Ischemia-reperfusion (IR) injury following lung transplantation remains a major source of early morbidity and mortality. Histologically, this inflammatory process is characterized by neutrophil infiltration and activation. We previously reported that lung IR injury was significantly attenuated in plasminogen activator inhibitor-1-deficient mice. In this study, we explored the potential role of tissue plasminogen activator (tPA) in a mouse lung IR injury model. As a result, tPA knockout (KO) mice were significantly protected from lung IR injury through several mechanisms. At the cellular level, tPA KO specifically blocked neutrophil extravasation into the interstitium, and abundant homotypic neutrophil aggregation (HNA) was detected in the lung microvasculature of tPA KO mice after IR. At the molecular level, inhibition of neutrophil extravasation was associated with reduced expression of platelet endothelial cell adhesion molecule-1 mediated through the tPA/ LDL receptor-related protein/NF-κB signaling pathway, whereas increased P-selectin triggered HNA. At the functional level, tPA KO mice incurred significantly decreased vascular permeability and improved lung function following IR. Protection from lung IR injury in tPA KO mice occurs through a fibrinolysis-independent mechanism. These results suggest that tPA could serve as an important therapeutic target for the prevention and treatment of acute IR injury after lung transplantation.
MRI of Coronary Wall Remodeling in a Swine Model of Coronary Injury Using an Elastin-Binding Contrast Agent
Authors: von Bary Christian , Makowski Marcus , Preissel Anne , Keithahn Alexandra , Warley Alice , Spuentrup Elmar , Buecker Arno , Lazewatsky Joel , Cesati Richard , Onthank David , Schickl Nikolaus , Schachoff Sylvia , Hausleiter Jörg , Schömig Albert , Schwaiger Markus , Robinson Simon , Botnar René
Published: March 2011

Background—

The extracellular matrix (ECM) plays an important role in the pathogenesis of atherosclerosis and in-stent restenosis. Elastin is an essential component of the ECM. ECM degradation can lead to plaque destabilization, whereas enhanced synthesis typically leads to vessel wall remodeling resulting in arterial stenosis or in-stent restenosis after stent implantation. The objective of this study was to demonstrate the feasibility of MRI of vascular remodeling using a novel elastin-binding contrast agent (BMS-753951).

Methods and Results—

Coronary injury was induced in 6 pigs by endothelial denudation and stent placement. At day 28, delayed-enhancement MRI coronary vessel wall imaging was performed before and after injection of gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA). Two days later, DE-MRI was repeated after administration of BMS-753951. Contrast-to-noise-ratio and areas of enhancement were determined. Delayed-enhancement MRI with BMS-753951 caused strong enhancement of the aortic, pulmonary artery, and injured coronary artery walls, whereas Gd-DTPA did not. Delayed-enhancement MRI of the stented coronary artery with BMS-753951 yielded a 3-fold higher contrast-to-noise-ratio when compared with the balloon-injured and control coronary artery (21±6 versus 7±3 versus 6±4;
P
<0.001). The area of enhancement correlated well with the area of remodeling obtained from histological data (
R
2
=0.86,
P
<0.05).

Conclusions—

We demonstrate the noninvasive detection and quantification of vascular remodeling in an animal model of coronary vessel wall injury using an elastin-specific MR contrast agent. This novel approach may be useful for the assessment of coronary vessel wall remodeling in patients with suspected coronary artery disease. Further studies in atherosclerotic animal models and degenerative ECM disease are now warranted.
Origins and Levels of Seasonal Forecast Skill for Sea Ice in Hudson Bay Using Canonical Correlation Analysis
Authors: Tivy Adrienne , Howell Stephen E. L. , Alt Bea , Yackel John J. , Carrieres Thomas
Published: March 2011

Canonical correlation analysis (CCA) is used to estimate the levels and sources of seasonal forecast skill for July ice concentration in Hudson Bay over the 1971–2005 period. July is an important transition month in the seasonal cycle of sea ice in Hudson Bay because it is the month when the sea ice clears enough to allow the first passage of ships to the Port of Churchill. Sea surface temperature (quasi global, North Atlantic, and North Pacific), Northern Hemisphere 500-mb geopotential height (z500), sea level pressure (SLP), and regional surface air temperature (SAT) are tested as predictors at 3-, 6-, and 9-month lead times. The model with the highest skill has three predictors—fall North Atlantic SST, fall z500, and fall SAT—and significant tercile forecast skill covering 61% of the Hudson Bay region.

The highest skill for a single-predictor model is from fall North Atlantic SST (6-month lead). Fall SST explains 69% of the variance in July ice concentration in Hudson Bay and a possible atmospheric link that accounts for the lagged relationship is presented. CCA diagnostics suggest that changes in the subpolar North Atlantic gyre and the Atlantic multidecadal oscillation (AMO), reflected in sea surface temperature, precedes a deepening/weakening of the winter upper-air ridge northwest of Hudson Bay. Changes in the height of the ridge are reflected in the strength of the winter northwesterly winds over Hudson Bay that have a direct impact on the winter ice thickness distribution; anomalies in winter ice severity are later reflected in the pattern and timing of spring breakup. July ice concentration in Hudson Bay has declined by approximately 20% per decade between 1979 and 2007, and the hypothesized link to the AMO may help explain this significant loss of ice.
Nutrition Disorders During Acute Renal Failure and Renal Replacement Therapy
Authors: Wiesen Patricia , Van Overmeire Lionel , Delanaye Pierre , Dubois Bernard , Preiser Jean‐Charles
Published: March 2011

The physiological and biological modifications related to acute renal failure in critically ill patients, including the current use of continuous renal replacement therapies, have dramatically changed the type and importance of the metabolic and nutrition disturbances observed during treatment of renal failure. This review summarizes the current knowledge and makes recommendations for the daily nutrition management of these patients. The filtration of water‐soluble substances of low molecular weight by continuous hemodiafiltration results in significant losses of glucose, amino acids, low‐molecular‐weight proteins, trace elements, and water‐soluble vitamins. The losses of these macronutrients and micronutrients should be compensated for. During continuous renal replacement therapy, the daily recommended energy allowance is between 25 and 35 kcal/kg, with a ratio of 60%–70% carbohydrates to 30%–40% lipids, and between 1.5 and 1.8 g/kg protein. Providing energy 25–35 kcal/kg/d with a carbohydrate/lipid ratio of 60–70/30–40 and protein 1.5–1.8 g/kg/d is recommended during continuous renal replacement therapy. Supplemental vitamin B1 (100 mg/d), vitamin C (250 mg/d), and selenium (100 mcg/d) are also recommended.
The Facilitated Early Enteral and Dietary Management Effectiveness Trial in Hospitalized Patients With Malnutrition
Authors: Somanchi Meena , Tao Xuguang , Mullin Gerard E.
Published: March 2011

Background: The prevalence of malnutrition in the hospitalized setting is 30% to 55%. Previous studies reported an association of malnutrition with an increased hospital length of stay (LOS), morbidity, and mortality of patients. This study evaluated the role of early nutrition intervention on LOS, diagnosis coding of malnutrition cases, calculating case mix index, and reducing delays in implementing nutrition support to patients. Methods: Demographic data, anthropometric measurements, LOS, and serum albumin levels were collected from 400 patients in 2 medical wards to determine the prevalence of malnutrition and potential delays in nutrition consultation. Based on these results, a nutrition intervention study was conducted in 1 ward; the other ward served as a control. Patients were classified as normally nourished or malnourished. Multivariate general linear regressions were used to reveal the impact of intervention on the change in LOS, controlling for other potential confounding factors on the cohort and a subset with severe malnutrition. Results: Of the 400 patients assessed, 53% had malnutrition. Multiple general linear regressions showed that nutrition intervention reduced LOS an average of 1.93 days in the cohort group and 3.2 days in the severe malnourished group. Case mix index and female gender were positively associated with LOS in the malnourished group. Nutrition intervention reduced the delays in implementing nutrition support to patients by 47%. Conclusions: Results highlight the positive impact of nutrition intervention in terms of reduced LOS in malnourished hospital patients. Reduction in LOS with diagnosis coding of malnutrition cases yielded substantial economic benefits.
Neurooncology
Authors: Bradley Alys E. , Keane Kevin
Published: March 2011

General session 4 of a 2010 scientific symposium sponsored jointly by the Society of Toxicologic Pathology and the International Federation of Societies of Toxicologic Pathologists considered the problem of primary neoplasms of the nervous system, especially the brain and spinal cord. Primary tumors of the nervous system account for a small but persistent fraction of cancers, occur disproportionately in juveniles, and are notoriously difficult to treat. This session explored new ideas and techniques with respect to the etiopathogenesis, diagnosis, and treatment of neural tumors with an emphasis on the translation of animal models of brain neoplasia and toxicology investigations for candidate therapeutic agents to the human situation. Additionally, this session covered current thinking on pharmaceutical discovery and safety assessment that is unique to this area of oncology.
The Top 10 Considerations in Pediatric Ossiculoplasty
Authors: Cushing Sharon L. , Papsin Blake C.
Published: March 2011

Pediatric ossiculoplasty presents the surgeon with a number of unique challenges relating, for example, to timing, choice of graft material, stabilization, and reconstruction. The aim of the current article is to review 10 important considerations in pediatric ossiculoplasty in an effort to maximize outcomes while minimizing complications. Routinely and systematically addressing each of these factors prior to and during ossiculoplasty in every pediatric patient will both optimize and contribute to understanding the hearing results achieved.
Murine Ciliotoxicity and Rabbit Sinus Mucosal Healing by Polyhydrated Ionogen
Authors: DePoortere David , Kofonow Jennifer M. , Chen Bei , Chiu Alexander G. , Cohen Noam A.
Published: March 2011

Objectives

Determine the toxicity and efficacy of a novel antiprotease topical irrigation, polyhydrated ionogen (PHI) ± MgBr2, in improving sinonasal remucosalization following surgery.

Study Design

Blinded, randomized controlled study.

Setting

Academic.

Subjects and Methods

Ciliary beat frequency (CBF) of murine nasal septal explants was continuously recorded before and after addition of PHI solution to asses for ciliotoxicity. To evaluate for efficacy in remucosalization, 9 New Zealand white rabbits underwent bilateral medial‐wall maxillary mucosal stripping followed by placement of an indwelling irrigation catheter. In a randomized fashion one side received 3 mL of normal saline (NS) daily, whereas the contralateral side received PHI ± MgBr2. Following a 14‐day therapeutic trial, remucosalization was assessed by hematoxylin and eosin staining and immunohistochemistry for β‐tubulin, a marker of cilia. A semiquantitative grading of ciliated remucosalization was applied with a chi‐square test to compare the saline with the PHI ± MgBr2 treatment.

Results

Safety evaluation of the PHI solutions demonstrated no evidence of ciliotoxicity. Histologic semiquantitative analysis of maxillary sinus remucosalization demonstrated significantly more ciliated epithelium (>60%) in the majority of PHI (n = 4) and PHI with MgBr2 (n = 5) treatment compared with the saline treatment (<30%) (n = 9). This was confirmed with immunohistochemical staining for type IV β‐tubulin a marker of respiratory cilia.

Conclusions

Success of functional endoscopic sinus surgery depends on restoration of normal mucociliary clearance. Topical PHI application has previously been demonstrated to significantly increase dermal wound healing. PHI solution is not ciliotoxic, and daily topical PHI or PHI MgBr2 irrigation enhances ciliated remucosalization compared with saline.
Start and acceleration optimization of a parallel hybrid electric vehicle
Authors: Wang C-L , Yin C-L , Luo G , Guo Z-Q , Gai F-X
Published: March 2011

The main issues relating to hybrid electric vehicle (HEV) emissions are starting and transient air-fuel ratio (AFR) control. The idle-cancelling function of an HEV will postpone the catalyst activation at cold start. So it is vital to confine the start emission to a much lower level. The conventional transient fuel also dramatically deteriorates emissions. The start and transient acceleration control strategies were developed on a uni-axis integrated starter–generator (ISG) parallel HEV. The optimization of each stage of the start process was realized. The start parameters of the engine controller (ECU) and vehicle controller (VCU) were determined by analysing unsuccessful starts. The results show that the engine starts smoothly without much speed overshoot. The AFR is superior to that of the prototype vehicle. At warming-up start and hot start there is also a smooth transition from ambient oxygen ratio to stoichiometric AFR. The concept is introduced of ‘fast’ and ‘slow’ torque to ISG boost acceleration. The conventional engine fuel wetting effect is overcome by ISG boost. The engine transient fuel and acceleration fuel compensation (AFC) for vehicle acceleration were replaced by ISG transient torque and continuous torque. The ISG boost acceleration calibration was completed and validated the result that the transient AFR was optimized without sacrificing vehicle drivability or acceleration performance. Both ISG start and ISG boost acceleration are effective approaches to solve the problem of HEV emission.
Parenting Training for Intellectually Disabled Parents: A Cochrane Systematic Review
Authors: Coren Esther , Thomae Manuela , Hutchfield Jemeela
Published: March 2011

Objectives: This article presents a Cochrane/Campbell systematic review of the evidence on the effect of parent training to support the parenting of parents with intellectual disabilities. Method: Randomized controlled trials (RCTs) comparing parent training interventions for parents with intellectual disability with usual care or with a control group were included in the review. Outcomes: The attainment of parenting skills specific to the intervention, safe home practices, and the understanding of child health were the outcomes of interest. Results: Three trials met the inclusion criteria. All three indicated improved parenting skills following parenting training. Conclusions: The quality of the evidence is moderate to low, with limited information available to assess possible bias. The presented evidence seems promising; however, there is a need for larger RCTs of interventions before conclusions can be drawn about the effectiveness of parent training for this group of parents.
Injection Drug Users’ Access to a Supervised Injection Facility in Vancouver, Canada: The Influence of Operating Policies and Local Drug Culture
Authors: Small Will , Shoveller Jean , Moore David , Tyndall Mark , Wood Evan , Kerr Thomas
Published: March 2011

North America’s first supervised injection facility (SIF) was established in Vancouver, Canada, in 2003. Although evaluation research has documented reductions in risk behavior among SIF users, there has been limited examination of the influence of operational features on injection drug users’ access to these facilities. We conducted an ethnographic study that included observational research within the SIF, 50 in-depth individual interviews with SIF users, and analysis of the regulatory frameworks governing the SIF. The government-granted exemption allowing the facility to operate legally imposes key operating regulations, as well as a cap on capacity, which results in significant wait times to enter the injecting room. Regulations that prohibit practices that are common in the local drug culture also negatively affect SIF utilization. Restructuring policies that shape the operation of the SIF could enhance access to the facility and permit SIF services to better accommodate local drug use practices.
Intergenerational Energy Balance Interventions: A Systematic Literature Review
Authors: Swanson Mark , Studts Christina R. , Bardach Shoshana H. , Bersamin Andrea , Schoenberg Nancy E.
Published: March 2011

Many nations have witnessed a dramatic increase in the prevalence of obesity and overweight across their population. Recognizing the influence of the household environment on energy balance has led many researchers to suggest that intergenerational interventions hold promise for addressing this epidemic. Yet few comprehensive reviews of intergenerational energy balance interventions have been undertaken. Our review of the literature over the past decade revealed that intergenerational intervention approaches to enhance energy balance use a broad array of designs, target populations, and theoretical models, making results difficult to compare and “best practices” challenging to identify. Additional themes include variation in how interventions incorporate the intergenerational component; an increasing acknowledgment of the importance of ecological models; variations in the location of interventions delivery; diversity in the intervention flexibility/structure, intensity, and duration; and variation in outcomes and measures used across studies. We discuss implications and future directions of intergenerational energy balance approaches.
Fetal and Neonatal Exposure to Nicotine Disrupts Postnatal Lung Development in Rats: Role of VEGF and Its Receptors
Authors: Petre Maria A. , Petrik Jim , Ellis Russ , Inman Mark D. , Holloway Alison C. , Labiris N. Renee
Published: March 2011

Many women are unable to quit smoking during pregnancy and therefore are prescribed drugs, including nicotine (nicotine replacement therapy [NRT]), to aid with smoking cessation. However, the consequences to the offspring of pregnant NRT users have not been well studied. The goals of this study were to determine the consequences of fetal and neonatal exposure to nicotine on lung development and function. Female rats were exposed to nicotine for 2 weeks prior to mating until weaning. Lungs were collected from saline and nicotine-treated rats from birth to adulthood to assess postnatal lung structure and function. Although nicotine exposure altered alveolarization at weaning, an effect that resolved by adulthood, it did not affect lung function at any of the ages investigated. However, nicotine exposure significantly decreased lung vascularization. The current study suggests that perinatal exposure to nicotine alters lung development, an effect which may be mediated via decreased vascular endothelial growth factor (VEGF) signaling.
Determinants of the Desire to Institutionalize in Alzheimer’s Caregivers
Authors: Gallagher Damien , Ni Mhaolain Aine , Crosby Lisa , Ryan Deirdre , Lacey Loretto , Coen Robert F. , Walsh Cathal , Coakley Davis , Walsh J. Bernard , Cunningham Conal , Lawlor Brian A.
Published: March 2011

Background: The desire to institutionalize is an important predictor of future institutionalization. Few studies have examined potentially modifiable caregiver characteristics which might be the focus of future interventional strategies. Methods: A total of 102 patient/caregiver dyads with Alzheimer’s disease (n = 84) or mild cognitive impairment were recruited through a memory clinic. Cross-sectional analyses of a range of patients, caregivers, and context of care-related characteristics were conducted. Results: Caregiver desire to institutionalize was significantly associated with a number of potentially modifiable variables including caregiver coping style, self-efficacy, depression, burden, and the presence of an unmet service need. In a multivariate analysis, caregiver burden, depression, and nonspousal status were the only significant independent predictors of caregiver desire to institutionalize in a model which correctly classified 80.4% of caregivers. Conclusions: Interventions which seek to reduce caregiver desire to institutionalize should adopt a multifactorial approach to reduce symptoms of burden and depression in caregivers.
Current and future treatment approaches for neuromyelitis optica
Authors: Collongues Nicolas , de Seze Jérôme
Published: March 2011

Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system (CNS) characterized by severe attacks of optic neuritis and myelitis, and which, unlike multiple sclerosis (MS), commonly spares the brain in the early stages. NMO used to be considered as a special form of MS. During the past 10 years, however, the two diseases have been shown to be clearly different. NMO is a B-cell-mediated disease associated with anti-aquaporin-4 antibodies in many cases and its pathophysiology seems to be near the acute lesion of necrotizing vasculitis. Assessment of prevalence shows that NMO is far less frequent than MS, which explains the absence of randomized clinical trials and NMO treatment strategies validated by evidence-based medicine. Recently, many data have been published that suggest that the therapeutic option in NMO should be immunosuppressive rather than immunomodulatory drugs. In the present study, after a brief overview of NMO, we review therapeutic studies and propose new therapeutic strategies in the relapse and disease-modifying fields.
The c-Myb target gene neuromedin U functions as a novel cofactor during the early stages of erythropoiesis
Authors: Gambone Julia E. , Dusaban Stephanie S. , Loperena Roxana , Nakata Yuji , Shetzline Susan E.
Published: March 2011

The requirement of c-Myb during erythropoiesis spurred an interest in identifying c-Myb target genes that are important for erythroid development. Here, we determined that the neuropeptide neuromedin U (NmU) is a c-Myb target gene. Silencing NmU, c-myb, or NmU's cognate receptor NMUR1 expression in human CD34+ cells impaired burst-forming unit-erythroid (BFU-E) and colony-forming unit-erythroid (CFU-E) formation compared with control. Exogenous addition of NmU peptide to NmU or c-myb siRNA-treated CD34+ cells rescued BFU-E and yielded a greater number of CFU-E than observed with control. No rescue of BFU-E and CFU-E growth was observed when NmU peptide was exogenously added to NMUR1 siRNA-treated cells compared with NMUR1 siRNA-treated cells cultured without NmU peptide. In K562 and CD34+ cells, NmU activated protein kinase C-βII, a factor associated with hematopoietic differentiation-proliferation. CD34+ cells cultured under erythroid-inducing conditions, with NmU peptide and erythropoietin added at day 6, revealed an increase in endogenous NmU and c-myb gene expression at day 8 and a 16% expansion of early erythroblasts at day 10 compared to cultures without NmU peptide. Combined, these data strongly support that the c-Myb target gene NmU functions as a novel cofactor for erythropoiesis and expands early erythroblasts.
The role of phosphatidylinositol 3-kinase-δ in the immunomodulatory effects of lenalidomide in chronic lymphocytic leukemia
Authors: Herman Sarah E. M. , Lapalombella Rosa , Gordon Amber L. , Ramanunni Asha , Blum Kristie A. , Jones Jeffrey , Zhang Xiaoli , Lannutti Brian J. , Puri Kamal D. , Muthusamy Natarajan , Byrd John C. , Johnson Amy J.
Published: March 2011

In patients with chronic lymphocytic leukemia (CLL), lenalidomide can promote humoral immune responses but also induces a distinct disease-specific toxicity of tumor flare and cytokine release. These CLL-specific events result from increased expression of costimulatory molecules on B cells. Here we demonstrate that lenalidomide activation of CLL cells depends on the phosphatidylinositol 3-kinase p110δ (PI3K-δ) pathway. Inhibition of PI3K-δ signaling by the PI3K-δ-inhibiting drug, CAL-101, or by siRNA knockdown of p110δ, abrogates CLL cell activation, costimulatory molecule expression, and vascular endothelial growth factor and basic fibroblast growth factor gene expression that is induced by lenalidomide. In addition, CAL-101 attenuates lenalidomide-mediated increases in immunoglobulin M production by normal B cells. Collectively, these data demonstrate the importance of PI3K-δ signaling for lenalidomide immune modulation. These findings may guide development of strategies for the treatment of CLL that combine lenalidomide with CAL-101, with other inhibitors of the PI3K-δ pathway, or with other agents that target downstream kinases of this signaling pathway.
Hematopoietic-Prostaglandin D2 synthase through PGD2 production is involved in the adult ovarian physiology
Authors: Farhat Andalib , Philibert Pascal , Sultan Charles , Poulat Francis , Boizet-Bonhoure Brigitte
Published: March 2011

Background

The prostaglandin D2 (PGD2) pathway is involved in numerous biological processes and while it has been identified as a partner of the embryonic sex determining male cascade, the roles it plays in ovarian function remain largely unknown. PGD2 is secreted by two prostaglandin D synthases (Pgds); the male-specific lipocalin (L)-Pgds and the hematopoietic (H)-Pgds.

Methods

To study the expression of the Pgds in the adult ovary, in situ hybridization were performed. Then, to evaluate the role of H-Pgds produced PGD2 in the ovarian physiology, adult female mice were treated with HQL-79, a specific inhibitor of H-Pgds enzymatic activity. The effects on expression of the gonadotrophin receptors FshR and LhR, steroidogenic genes Cyp11A1, StAR and on circulating progesterone and estradiol, were observed.

Results

We report the localization of H-Pgds mRNA in the granulosa cells from the primary to pre-ovulatory follicles. We provide evidence of the role of H-Pgds-produced PGD2 signaling in the FSH signaling through increased FshR and LhR receptor expression. This leads to the activation of steroidogenic Cyp11A1 and StAR gene expression leading to progesterone secretion, independently on other prostanoid-synthetizing mechanisms. We also identify a role whereby H-Pgds-produced PGD2 is involved in the regulation of follicular growth through inhibition of granulosa cell proliferation in the growing follicles.

Conclusions

Together, these results show PGD2 signaling to interfere with FSH action within granulosa cells, thus identifying an important and unappreciated role for PGD2 signaling in modulating the balance of proliferation, differentiation and steroidogenic activity of granulosa cells.
Stowe, Byron, and the Art of Scandal
Authors: Ryan Susan M.
Published: March 2011

The media firestorm that followed Harriet Beecher Stowe's exposé of Lord Byron's supposed incest (which she first detailed in an 1869 Atlantic Monthly article and later in the book Lady ByronVindicated [1870]) provides an apt cultural site for analyzing the intersections among notions of authorship, moral authority, and literary value in the second half of the nineteenth century. Noting that a significant strain of commentary on the scandal sought to separate Byron's literary genius from the matter of his personal behavior, Ryan argues that this case study allows us to situate the declining relevance of authorial character to the question of literary valuation rather earlier in the century than scholars have typically claimed. Further, the Stowe-Byron scandal prefigures the unevenness and contestation that would accompany that development as well as the degree to which it would be complicated by the very identity categories and political investments that such a text-centered approach seems intent on eliding. Ryan notes that book advertisements and other archival sources support the view—advanced by both nineteenth-century commentators and twentieth-century scholars—that the scandal enhanced Byron's status and sales. The ensuing damage to Stowe's career, on the other hand, has been much exaggerated. The article concludes by exploring the critical and pedagogical tensions that authorship's reputational economies still engender.
Organic Shrapnel: Affect and Aesthetics in September 11 Fiction
Authors: Smith Rachel Greenwald
Published: March 2011

Smith's essay examines history, politics, and literary form in September 11 fiction. It begins with the contention that the traditionally conceived relationship between trauma and form poses a problem for the analysis of September 11 fiction. It is often posited that traumatic events produce formal changes in narrative strategies that reflect transformations in historical and political thinking, but many 9/11 novels, like Don DeLillo's Falling Man, do not demonstrate significant formal departures from pre-9/11 works. Others, like Jonathan Safran Foer's Extremely Loud and IncrediblyClose, offer gestures toward formal innovation but ultimately support sentiments that are tied to a regressive view of history. Yet in turning to a less commonly considered work of September 11 fiction, Laird Hunt's experimental noir The Exquisite, the essay offers another way of thinking about the role of form in relation to political change. Hunt's work shows that formal innovations—in this case, a particularly strange use of ecological metaphor—need not merely reflect historical ruptures, but can also be understood to produce bodily affects that are themselves constitutive of altered attitudes toward the present.
A functional analysis of MELK in cell division reveals a transition in the mode of cytokinesis during Xenopus development
Authors: Le Page Yann , Chartrain Isabelle , Badouel Caroline , Tassan Jean-Pierre
Published: March 2011

MELK is a serine/threonine kinase involved in several cell processes, including the cell cycle, proliferation, apoptosis and mRNA processing. However, its function remains elusive. Here, we explored its role in the Xenopus early embryo and show by knockdown that xMELK (Xenopus MELK) is necessary for completion of cell division. Consistent with a role in cell division, endogenous xMELK accumulates at the equatorial cortex of anaphase blastomeres. Its relocalization is highly dynamic and correlates with a conformational rearrangement in xMELK. Overexpression of xMELK leads to failure of cytokinesis and impairs accumulation at the division furrow of activated RhoA – a pivotal regulator of cytokinesis. Furthermore, endogenous xMELK associates and colocalizes with the cytokinesis organizer anillin. Unexpectedly, our study reveals a transition in the mode of cytokinesis correlated to cell size and that implicates xMELK. Collectively, our findings disclose the importance of xMELK in cytokinesis during early development and show that the mechanism of cytokinesis changes during Xenopus early development.
Cytoplasmic intermediate filaments mediate actin-driven positioning of the nucleus
Authors: Dupin Isabelle , Sakamoto Yasuhisa , Etienne-Manneville Sandrine
Published: March 2011

The localization of the nucleus is precisely regulated, and defects in nuclear positioning are observed in diseases such as lissencephaly, cerebellar ataxia and dysplasia. We show here that cytoplasmic intermediate filaments are essential players in actin-dependent positioning of the nucleus. The actin retrograde flow is relayed by a flow of intermediate filaments that accumulate asymmetrically around the nuclear envelope. Perturbations of the intermediate filament network alter positioning of the nucleus in both migrating and immobile astrocytes. This function of intermediate filaments might be crucial for regulating cell motility, in particular in tumor cells expressing high levels of cytoplasmic intermediate filaments.
Affirmative Warnings may be Better Understood than Negative Warnings; Standard Neonatal Intensive Care Unit Drug Infusion Concentrations; Limits Placed on Prescription Transfers by Patients; Top Drugs that Cause Violence; Vincristine Caution Statement Reworded
Authors: Cohen Michael R. , Smetzer Judy L.
Published: March 2011

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs.

Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers' names will be published if desired. ISMP may be contacted at the address shown below.

Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site ( www.ismp.org ), by calling 800-FAIL-SAFE, or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters' wishes as to the level of detail included in publications.
Acute Encephalomyelitis Syndromes Associated with H1N1 Influenza Vaccinations; Erythema Multiforme Secondary to H1N1 Vaccine; Cytolytic Hepatitis Possibly Related to Oral Contraceptives; Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome Associated with Lamotrigine: First Report; Behavioral Disinhibition with Baclofen; Minoxidil-Induced Trichostasis Spinulosa of Terminal Hair; Delayed-Onset Mirtazapine-Related Leukopenia
Authors: Shuster Joel
Published: March 2011

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers.
Evaluation of Recombinant Factor VIIa Off-Label Use at an Acute Care Hospital with Established Guidelines for Use
Authors: Allen John , Alexander Earnest
Published: March 2011

Purpose

At present, there are a scarcity of data available evaluating off-label prescribing patterns of recombinant factor VIIa (rFVIIa), pharmacoeconomic impact, and patient outcomes in clinical practice in an acute care setting with guidelines in place to influence prescribing practices. The primary objective of this study was to retrospectively evaluate the off-label usage and prescribing patterns of rFVIIa at a large acute care hospital with established rFVIIa guidelines.

Results

During the study period, a total of 199 patients were ordered rFVIIa, of which 181 (91%) received at least one dose of rFVIIa for an off-label use (n=181). Refractory bleeding and intracerebral hemorrhage were the 2 leading uses for rFVIIa, accounting for 30% (n = 54) and 29% (n = 51) of all uses, respectively. Overall, the mean number of doses per patient for all uses was 1.79. The mean number of doses per patient by non–FDA-approved use was highest in patients with cardiac surgery and refractory bleeding. The total yearly acquisition of rFVIIa for the study institution has decreased from 5.25 mcg/patient-day in 2005 to 2.52 mcg/patient-day in 2009.

Conclusion

The findings are encouraging and support the impact that education of pharmacy, nursing, and physician staff along with guideline development may have on off-label rFVIIa usage. Further research evaluating the impact of rFVIIa guidelines and/or order sets is warranted.
Developing Patient-Centered Services, Part 3: The Ohio State University Medical Center
Authors: Siegel Jerry , Weber Robert J.
Published: March 2011

The Director's Forum series is edited by Robert J. Weber and Scott M. Mark and is designed to guide pharmacy leaders in establishing patient-centered services in hospitals and health systems. This month's article continues the theme of practice model development. This focus is mainly a result of health-system pharmacy's emphasis on changing pharmacy practice by moving pharmacists closer to patients and by utilizing technicians to ensure optimal quality control of the medication use system. This article gives the pharmacy director another example of a practice model that employs a hybrid approach. These examples can be used as a foundation for growing patient-centered pharmacy services in your organization.
Contribution of microbiology to an effective control of healthcare-associated infections
Authors: Barcs István , Kovács Aranka , Antmann Katalin , Becker Anita , Domján Gyula
Published: March 2011

An effective control of healthcare-associated infections is not realized without an intensive participation of microbiologic activities. Authors present the model of a centre for healthcare-associated infection control established in 2008 at Semmelweis University. The new model of the surveillance system is based on diagnostic and experimental microbiologic data. Clinical and epidemiological microbiologic examinations are performed in the same laboratory using identical methods, and the results are continually compared. Reports consist of two functional parts; namely list of pathogens isolated and antibiotic sensitivity patterns for clinicians and messages especially for epidemiologists including abbreviated information on bacteria of nosocomial importance. Rapid detection of the most important pathogens both from clinical samples and from those obtained for detecting nasal carriage is carried out by a sensitive and specific method of an automated real time PCR. Biotyping of isolates by detailed biochemical substrate spectrum, genotyping by ready-to-use kits depending on polymorphism of repetitive DNA sequences, and cluster analysis of data are used for up-to-date survey of nosocomial situation. Statistical analysis of reports is performed by the multifactorial software OSIRIS Epidemiology. Orv. Hetil., 2011, 152, 437–442.
Sedation and analgesia during gastrointestinal endoscopy
Authors: Müllner Katalin , Tulassay Zsolt
Published: March 2011

Sedative and analgesic premedication is frequently used during gastrointestinal endoscopy. Sedation improves patient’s compliance, helping the examinations and their safe completion, but it lengthens the procedures, increases the costs, and complications can occur. Sedative drugs are applied during upper and lower gastrointestinal endoscopy, and also at ERCP. The review summarizes the different forms of sedation, drugs, future techniques and possibilities of improvements. Moreover, sedation practice in Hungary is also described. Orv. Hetil., 2011, 152, 428–436.
The Microstructure and Chemistry of the Reaction between Ti and α-Al2O3
Authors: Selverian J. H. , Bortz M. , Ohuchil F. S. , Notis M. R.
Published: March 2011

The Ti/Al2O3 system is being considered for advanced aerospace applications and is important in microelectronics where Ti is used for metallization on Al2O3 substrates. We have studied the intrinsic reactivity of Ti with the R-plane (1012) surface of α-Al2O3 by x-ray photoemission spectroscopy (XPS) and transmission electron microscopy (TEM) techniques. XPS results indicate that a for deposition of several monolayers of Ti at 25 °C, the Ti reduces the Al2O3 surface to produce Ti-O bonds. At 1000 °C the Ti reduces the Al2O3 to produce Ti-O and Ti-Al bonds. Cross-section TEM specimens were prepared from 200 nm thick Ti films deposited on Al2O3 at 25 and 800 °C to observe the interface region. In samples deposited at 25 and 800 °C, without further annealing, no reaction zone could be seen in the TEM. Ordered Ti3Al (78 ± 5 Ti, 16 ± 3 Al and 6 ± 3 0 wt pct) was observed in a sample deposited at 25 °C and annealed at 800 °C for 2 hours.
Resin Selection Criteria for Molded Electronic Packages
Authors: Rimsa S. B.
Published: March 2011

The selection of the proper resin system for a molded PWB or electronic package must take into account considerably more parameters than simply the cost of and the ability of the polymer to fill the tooling. Molding of an electronic package is only the initial step in a multi stage sequence to produce a functional PWB or interconnect device.

It is of extreme importance that a manufacturer of molded electronic packages understand not only the fabrication properties of a resin, but also those mechanical, thermal, and chemical requirements of the circuit application and assembly operations.

A specific circuitry application process will usually require a specific set of substrate characteristics. These performance characteristics may relate to platability, thermal stability, modulus, compressive strength, or even adhesive bondability for a given procedure. The substrate requirements for several popular circuit application methods is reviewed.

Assembly presents perhaps the most demanding area of resin performance in electronic package or PWB fabrication. The thermal stresses encountered in wave soldering and vapor phase reflow will quickly differentiate among current engineering resin offerings. The importance of controlled moisture absorption and high temperature modulus retention is explored in addition to end use environmental factors which can be of special concern.