bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of respiration variations on independent component analysis results of resting state functional connectivity
Authors: Birn Rasmus M. , Murphy Kevin , Bandettini Peter A.
Published: April 2008

The analysis of functional connectivity in fMRI can be severely affected by cardiac and respiratory fluctuations. While some of these artifactual signal changes can be reduced by physiological noise correction routines, signal fluctuations induced by slower breath‐to‐breath changes in the depth and rate of breathing are typically not removed. These slower respiration‐induced signal changes occur at low frequencies and spatial locations similar to the fluctuations used to infer functional connectivity, and have been shown to significantly affect seed‐ROI or seed‐voxel based functional connectivity analysis, particularly in the default mode network. In this study, we investigate the effect of respiration variations on functional connectivity maps derived from independent component analysis (ICA) of resting‐state data. Regions of the default mode network were identified by deactivations during a lexical decision task. Variations in respiration were measured independently and correlated with the MRI time series data. ICA appears to separate the default mode network and the respiration‐related changes in most cases. In some cases, however, the component automatically identified as the default mode network was the same as the component identified as respiration‐related. Furthermore, in most cases the time series associated with the default mode network component was still significantly correlated with changes in respiration volume per time, suggesting that current methods of ICA may not completely separate respiration from the default mode network. An independent measure of the respiration provides valuable information to help distinguish the default mode network from respiration‐related signal changes, and to assess the degree of residual respiration related effects. Hum Brain Mapp 2008. © 2008 Wiley‐Liss, Inc.
Dynamical consequences of lesions in cortical networks
Authors: Honey Christopher J. , Sporns Olaf
Published: April 2008

To understand the effects of a cortical lesion it is necessary to consider not only the loss of local neural function, but also the lesion‐induced changes in the larger network of endogenous oscillatory interactions in the brain. To investigate how network embedding influences a region's functional role, and the consequences of its being damaged, we implement two models of oscillatory cortical interactions, both of which inherit their coupling architecture from the available anatomical connection data for macaque cerebral cortex. In the first model, node dynamics are governed by Kuramoto phase oscillator equations, and we investigate the sequence in which areas entrain one another in the transition to global synchrony. In the second model, node dynamics are governed by a more realistic neural mass model, and we assess long‐run inter‐regional interactions using a measure of directed information flow. Highly connected parietal and frontal areas are found to synchronize most rapidly, more so than equally highly connected visual and somatosensory areas, and this difference can be explained in terms of the network's clustered architecture. For both models, lesion effects extend beyond the immediate neighbors of the lesioned site, and the amplitude and dispersal of nonlocal effects are again influenced by cluster patterns in the network. Although the consequences of in vivo lesions will always depend on circuitry local to the damaged site, we conclude that lesions of parietal regions (especially areas 5 and 7a) and frontal regions (especially areas 46 and FEF) have the greatest potential to disrupt the integrative aspects of neocortical function. Hum Brain Mapp, 2008. © 2008 Wiley‐Liss, Inc.
Modulation of temporally coherent brain networks estimated using ICA at rest and during cognitive tasks
Authors: Calhoun Vince D. , Kiehl Kent A. , Pearlson Godfrey D.
Published: April 2008

Brain regions which exhibit temporally coherent fluctuations, have been increasingly studied using functional magnetic resonance imaging (fMRI). Such networks are often identified in the context of an fMRI scan collected during rest (and thus are called “resting state networks”); however, they are also present during (and modulated by) the performance of a cognitive task. In this article, we will refer to such networks as temporally coherent networks (TCNs). Although there is still some debate over the physiological source of these fluctuations, TCNs are being studied in a variety of ways. Recent studies have examined ways TCNs can be used to identify patterns associated with various brain disorders (e.g. schizophrenia, autism or Alzheimer's disease). Independent component analysis (ICA) is one method being used to identify TCNs. ICA is a data driven approach which is especially useful for decomposing activation during complex cognitive tasks where multiple operations occur simultaneously. In this article we review recent TCN studies with emphasis on those that use ICA. We also present new results showing that TCNs are robust, and can be consistently identified at rest and during performance of a cognitive task in healthy individuals and in patients with schizophrenia. In addition, multiple TCNs show temporal and spatial modulation during the cognitive task versus rest. In summary, TCNs show considerable promise as potential imaging biological markers of brain diseases, though each network needs to be studied in more detail. Hum Brain Mapp, 2008. © 2008 Wiley‐Liss, Inc.
In vivo antisense oligonucleotide reduction of NPC1 expression as a novel mouse model for Niemann Pick type C– associated liver disease
Authors: Rimkunas Victoria M. , Graham Mark J. , Crooke Rosanne M. , Liscum Laura
Published: April 2008

Niemann-Pick type C (NPC) is a fatal autosomal recessive lipidosis that is characterized by lysosomal storage of cholesterol and glycosphingolipids. Patients exhibit prolonged neonatal jaundice, hepatosplenomegaly, and progressive neurodegeneration that generally result in death by the teen years. Most clinical cases are caused by mutations in theNPC1gene. Current mouse models of NPC are not well suited for studying the liver disease due to the rapidly progressing neurological disease. To facilitate study of NPC-associated liver dysfunction, we have developed a novel mouse model using antisense oligonucleotides to ablate NPC1 expression primarily in the liver. Here, we show that the NPC1 knockdown leads to a liver disease phenotype similar to that of patients with NPC and the NPCnih mouse model. Key features include hepatomegaly, lipid storage, elevated serum liver enzymes, and increased apoptosis.Conclusion:This novel NPC1 antisense mouse model will allow delineation of the mechanism by which NPC1 dysfunction leads to liver cell death.
Is major depressive disorder a metabolic encephalopathy?
Authors: Harvey Brian H
Published: April 2008

Metabolic encephalopathy is an acute disturbance in cellular metabolism in the brain evoked by conditions of hypoxia, hypoglycaemia, oxidative stress and/or inflammation. It usually develops acutely or subacutely and is reversible if the systemic disorder is treated. If left untreated, however, metabolic encephalopathy may result in secondary structural damage to the brain. Most encephalopathies are present with neuropsychiatric symptoms, one in particular being depression. However, mood disorders are often co‐morbid with cardiovascular, liver, kidney and endocrine disorders, while increasing evidence concurs that depression involves inflammatory and neurodegenerative processes. This would suggest that metabolic disturbances resembling encephalopathy may underscore the basic neuropathology of depression at a far deeper level than currently realized. Viewing depression as a form of encephalopathy, and exploiting knowledge gleaned from our understanding of the neurochemistry and treatment of metabolic encephalopathy, may assist in our understanding of the neurobiology of depression, but also in realizing new ideas in the pharmacotherapy of mood disorders. Copyright © 2008 John Wiley & Sons, Ltd.
Degradation of biorefractory furaltadone in aqueous solution by ozonation
Authors: Bao Nan , Sun Jian , Wei Zhen‐Tao , Ma Dong , Liu Feng , Wang Jin
Published: April 2008

BACKGROUND: Furaltadone (FD), a nitrofuran derivative, is a highly effective chemotherapeutic drug. In China the FD wastewater discharged by the pharmaceutical industry is high in organics and biorefractory compounds. The objective of this study was to investigate the degradation mechanism of FD in aqueous solution by ozone oxidation. Preliminary results on the reaction mechanism were obtained using three different spectral analysis techniques.

RESULTS: The ozonation mechanism was significantly affected by the pH value. At low pH values the primary reaction is direct oxidation of ozone, an incomplete oxidisation, which can only destroy the FD molecule's conjugated structure. At high pH values the major reaction changes to hydroxyl radical oxidation. FD can be rapidly oxidised into CO2, H2O, NH3, NO$_{3}^{-}$, HCHO, oxalic acid and other aliphatic acids of low molecular weight, which can be entirely mineralised by continued ozonation.

CONCLUSION: The pH value significantly influences the mode of FD ozonation. The present experiment suggests a potentially useful pretreatment method for conventional biological treatment of wastewater containing FD. Copyright © 2008 Society of Chemical Industry
Not the usual cardiac rhythm device infection: A fastidious pathogen with several teaching points
Authors: Cawley Peter J. , Ravindrin Bipin K. , Poole Jeanne E.
Published: April 2008

Because cardiac device infections may include fastidious pathogens, extended incubation of blood cultures is suggested. A patient with an infection of a right ventricular lead implantable cardioverter defibrillator (ICD) system is described. The device was implanted 6 months earlier. The pathogen was identified as Haemophilus parainfluenzae, which was cultured within 72 hours and was presumably from a respiratory tract infection. Extended incubation was not necessary to culture this fastidious pathogen. Two large retrospective studies suggest that prolonged incubation for fastidious organisms is generally not necessary because of advances in culture media and automated blood culture systems. Journal of Hospital Medicine 2008;3:173–175. © 2007 Society of Hospital Medicine.
Fate of patients with obstructive jaundice
Authors: Björnsson Einar , Gustafsson Jonas , Borkman Jakob , Kilander Anders
Published: April 2008

BACKGROUND/OBJECTIVE:

Systematic data are limited on the etiology and prognosis of unselected patients with obstructive jaundice (OJ). We aimed to review the clinical features, etiology, and prognosis of patients with OJ.

METHODS:

All adult patients with bilirubin ≥ 5.85 mg/dL (100 μmol/L) at a university hospital in Sweden in 2003–2004 were identified. Medical records from patients with OJ were reviewed.

RESULTS:

Seven hundred and forty‐nine patients were identified, of whom 241 (32%) had OJ (median age 71 years, 129 women). No one was lost to follow‐up. The biliary obstruction of 154 patients (64%) was a result of a malignancy: 69 patients (46%) had pancreatic cancer, 44 (29%) had cholangiocarcinoma (CC), 5 (3%) had papilla vateri cancers, and 36 patients (23%) had other malignancies. Of the 87 patients with a benign obstruction, 57 (65%) had choledocholithiasis, 7 (8%) had biliary strictures, 6% had PSC, and the obstruction of 16 patients (20.7%) had other causes. A total of 115 of the 242 patients (48%) had abdominal pain associated with jaundice, whereas 52% had painless jaundice. Thirty‐four percent of patients with a malignant obstruction had abdominal pain versus 71% of patients with a benign obstruction (P < .05). At the end of follow‐up, only 5% (8 patients) with a malignant obstruction were alive versus 78% with a benign obstruction.

CONCLUSIONS:

Obstructive jaundice was the cause of the severe jaundice of one third of patients. Most cases of OJ were a result of a malignancy, which carried a very poor prognosis, with a 2‐year mortality rate of 95%. Journal of Hospital Medicine 2008;3:117–123. © 2008 Society of Hospital Medicine.
Diagnostic and treatment delays in recurrent clostridium difficile–associated disease
Authors: Scheurer Danielle
Published: April 2008

BACKGROUND:

Because Clostridium difficile–associated disease (CDAD) is primarily an inpatient issue, hospitalists are at the forefront of the timely diagnosis and treatment of patients with this disease.

DESIGN:

The study was a retrospective cohort of all inpatients with CDAD at Brigham and Women's Hospital from 1997 to 2004 in order to determine the time to diagnosis and treatment in initial and recurrent episodes of disease.

RESULTS:

The mean time to sampling, between 2.09 and 2.24 days, was not significantly different between initial and recurrent CDAD hospital episodes. The mean time to treatment (from symptoms and sampling) was shorter in recurrent episodes but was still 2.5 days.

CONCLUSIONS:

Patients with recurrent disease were more likely to be treated earlier but not diagnosed earlier than those with initial disease. Because both groups had significant diagnostic and treatment delays, this is an area in which hospitalists can have a major impact on patient care. Journal of Hospital Medicine 2008;3:156–159. © 2008 Society of Hospital Medicine.
Effect of a hospitalist–care coordinator team on a nonteaching hospitalist service
Authors: O'Leary Kevin J. , Lindquist Lee A. , Colone Marcia A. , Haviley Corinne , Thompson Jason A. , Baker David W.
Published: April 2008

BACKGROUND:

Although many hospitalists work with clinical coordinators, few studies have evaluated their impact.

OBJECTIVE:

The purpose of the study was to evaluate the impact of a hospitalist–care coordinator team on hospitalist work experience, patient satisfaction, and hospital efficiency.

DESIGN AND PARTICIPANTS:

During each of 12 weeks, hospitalists on a nonteaching hospitalist service were randomly assigned to work with a hospitalist care coordinator (HCC) or to work independently.

MEASUREMENTS:

Each week hospitalists completed a survey to assess their satisfaction and perceived work efficiency. Patient satisfaction with hospital discharge was assessed by telephone interviews. Hospital efficiency was analyzed with multivariate linear regression using log‐transformed length of stay (LOS) and cost as dependent variables.

RESULTS:

The 356 patients cared for by hospitalist–HCC teams were similar to 337 patients cared for by control hospitalists. Twenty‐eight of 31 hospitalists (90%) who worked with an HCC responded that the HCC improved their efficiency and job satisfaction. Seventy‐one of 196 eligible patients (36%) completed the postdischarge interview. The mean ratings of overall satisfaction with hospital discharge on a scale of 10 were similarly high in both groups (8.57 vs. 8.37; P = .94). In multivariate regression analyses, LOS was 0.28 days shorter and cost was $585.62 lower for patients cared for by hospitalist–HCC teams; however, these results were not statistically significant (P = .17 and .15, respectively).

CONCLUSIONS:

Hospitalists working in a team approach with an HCC reported improved efficiency and job satisfaction compared with hospitalists working independently. These findings are important in light of growing concerns about hospitalist workload and job satisfaction. Journal of Hospital Medicine 2008;3:103–109. © 2008 Society of Hospital Medicine.
Use of dexmedetomidine for sedation of children hospitalized in the intensive care unit
Authors: Carroll Christopher L. , Krieger Diane , Campbell Margaret , Fisher Daniel G. , Comeau Leonard L. , Zucker Aaron R.
Published: April 2008

BACKGROUND:

Dexmedetomidine is a potentially useful sedative for hospitalized children, but there is little published data regarding its safety, dosage, or efficacy.

OBJECTIVE:

To report our experience with dexmedetomidine for the sedation of hospitalized children.

DESIGN:

Retrospective case series.

SETTING:

Pediatric ICU of a university‐affiliated children's hospital.

PATIENTS:

We retrospectively examined data from the medical records of all children who received dexmedetomidine for sedation between December 2003 and October 2005.

INTERVENTION:

None.

RESULTS:

Dexmedetomidine was administered 74 times to 60 children (median age 1.5 years, range 0.1–17.2 years). The most common indications for ICU admission were respiratory distress/failure (53%), status–postcorrective cardiac surgery (19%), and other postoperative patients (18%). In 53% of cases dexmedetomidine was used to supplement ongoing sedation judged inadequatem and in 41% of cases it was used as a bridge to extubation while other sedatives were weaned or discontinued. Among all the children, the median dose to maintain adequate sedation was 0.7 μg/kg per hour (range 0.2–2.5 μg/kg per hour), with a median duration of therapy of 23 hours (range 3–451 hours). Most children (80%) experienced no adverse effects from the sedation, with hypotension (9%), hypertension (8%), and bradycardia (3%) the most common adverse events. For 93% of children who experienced a side effect, it resolved either without treatment or by withholding the infusion.

CONCLUSIONS:

In this cohort of children hospitalized in the ICU, dexmedetomidine appeared to be effective and to have few adverse effects. Dexmedetomidine may have a potentially useful role to play in sedating hospitalized children. Journal of Hospital Medicine 2008;3:142–147. © 2008 Society of Hospital Medicine.
Potentially inappropriate medication use in hospitalized elders
Authors: Rothberg Michael B. , Pekow Penelope S. , Liu Fengjuan , Korc‐Grodzicki Beatriz , Brennan Maura J. , Bellantonio Sandra , Heelon Mark , Lindenauer Peter K.
Published: April 2008

BACKGROUND:

Prescribing of potentially harmful medications has not been well documented in hospitals.

OBJECTIVE:

The objective of the study was to determine the rate of and factors associated with potentially inappropriate medication (PIM) prescribing in a large inpatient sample.

DESIGN:

The study was a retrospective cohort of the period between September 1, 2002, and June 30, 2005. We used multivariable logistic regression to identify patient, physician, and hospital characteristics associated with PIM prescribing.

SETTING:

The study collected data from 384 US hospitals.

PATIENTS:

The sample was composed of patients aged ≥65 years admitted with 1 or more of 7 common medical diagnoses.

MEASUREMENTS:

The percentage of patients prescribed PIMs as defined using a modified Beers list was measured. Multivariable‐adjusted odds ratios for PIM use were computed.

RESULTS:

Of the 493,971 patients, 49% received at least 1 PIM, and 6% received 3 or more, most commonly promethazine, diphenhydramine, and propoxyphene. Patient, physician, and hospital characteristics were all associated with PIM use. Patients with myocardial infarction or heart failure were most likely (61% and 52% vs. 46% for pneumonia), men (47% vs. 49% for women) and those in managed care plans (44% vs. 49% for other plans) were less likely, and patients ≥85 years were least likely (42% vs. 53% for patients aged 65–74 years) to receive PIMs (P < .0001 for all comparisons). For high‐severity PIMs, internists and hospitalists had similar prescribing rates (33%), cardiologists had a higher rate (48%), and geriatricians had the lowest rate (24%). The proportion of elders receiving PIMs ranged from 34% in the Northeast to 55% in the South, and variation at the individual hospital level was extreme. At 7 hospitals, PIMs were never prescribed.

CONCLUSIONS:

Wide variation in the use of PIMs is associated with hospital and physician characteristics. Care may be improved by minimizing this non‐patient‐centered variation. Journal of Hospital Medicine 2008;3:91–102. © 2008 Society of Hospital Medicine.
Innovative approaches to increase deep vein thrombosis prophylaxis rate resulting in a decrease in hospital‐acquired deep vein thrombosis at a tertiary‐care teaching hospital
Authors: Bullock‐Palmer Renee P. , Weiss Steven , Hyman Charles
Published: April 2008

BACKGROUND AND OBJECTIVE:

Hospital‐acquired venous thromboembolic events (VTEs) in medically ill patients account for a significant percentage of in‐hospital mortality. Unfractionated heparin and low‐molecular‐weight heparin have been shown to be effective in the prevention of VTEs. However, use of these medications for thromboprophylaxis remains suboptimal. The objective of this article is to report the impact of a continuous quality improvement project on adherence with DVT prophylaxis guidelines and on the subsequent incidence of hospital‐acquired DVT in medical patients at a teaching hospital between 2002 and 2005.

METHODS:

In November 2002, Kings County Hospital Center Department of Medicine embarked on a project to increase the rate of thromboprophylaxis use. Quality improvement strategies included an active, multifaceted, layered combination of provider education, provider reminders with decision support, and audit with feedback.

RESULTS:

The DVT prophylaxis rate on the general medicine house‐staff service increased from a baseline of 63% in 2002 to 96% in 2005. The number of hospital‐acquired DVTs decreased from a baseline of 14 in 2002 to 1 in 2005. The hospital‐acquired DVT rate fell significantly, from 2.6 per 1000 discharges in 2002 (95% CI 1.5–4.4) to 0.2 per 1000 discharges in 2005 (95% CI 0.0–1.1), P = .007.

CONCLUSIONS:

A layered combination of provider education, provider reminders with decision support, and audit with feedback increased the DVT prophylaxis rate and decreased the rate of hospital‐acquired DVTs in the medicine department at a tertiary‐care hospital center. Journal of Hospital Medicine 2008;3:148–155. © 2008 Society of Hospital Medicine.
The larval stages of the sea urchin, Strongylocentrotus purpuratus
Authors: Smith M. Meighan , Cruz Smith Luisa , Cameron, R. Andrew , Urry Lisa A.
Published: April 2008

The adult body plan of Strongylocentrotus purpuratus is established within the imaginal rudiment during the larval stages. To facilitate the study of these stages, we have defined a larval staging scheme, which consists of seven stages: Stage I, four‐arm stage; Stage II, eight‐arm stage; Stage III, vestibular invagination stage; Stage IV, rudiment initiation stage; Stage V, pentagonal disc stage; Stage VI, advanced rudiment stage; and Stage VI, tube‐foot protrusion stage. Each stage is characterized by significant morphological features observed for the first time at that stage. This scheme is intended as a guide for determining the degree of larval development, and for identifying larval and adult structures. Larval anatomy was visualized using light and confocal microscopy as required on living material, whole mount fixed specimens, and serial sections. Antibody staining to localize specific gene products was also used. Detailed analysis of these data has furthered our understanding of the morphogenesis of the rudiment, and has suggested provocative questions regarding the molecular basis for these events. We intend this work to be of use to investigators studying gene expression and morphogenesis in postembryonic larvae. J. Morphol., 2008. © 2008 Wiley‐Liss, Inc.
Investigation of hatching and early post‐embryonic life of freshwater crayfish by in vitro culture, behavioral analysis, and light and electron microscopy
Authors: Vogt Günter
Published: April 2008

The late embryonic and early post‐embryonic life period of freshwater crayfish, which is the main time period of organogenesis, is poorly investigated because of the protective brooding behavior of crayfish mothers. A combination of in vitro culture, behavioral observations, and microscopic investigations of organs involved in hatching, attachment, exploration of the environment, and searching and processing of food yielded deeper insights in this important period of life. Experiments were performed with the robust parthenogenetic marbled crayfish. The following results were obtained: (1) Marbled crayfish can be raised in simple in vitro systems from 80% embryonic development to juvenile Stage 4 with up to 100% survival; (2) Hatching is prepared by chemical weakening of the egg shell and completed by levering actions of the hatchling's appendages; (3) The telson thread, a safety line that keeps the hatchling secured to the mother, is formed by secretions from the telson and the detaching inner layer of the egg case; (4) Molting Stage‐1 juveniles are secured by an anal thread that results from delayed molting of the hindgut; (5) Active attachment of the hatchlings to the maternal pleopods with their 1st pereiopods is achieved by an innate fixed action pattern; (6) In vitro, juveniles are motile from Stage 2 despite incomplete development of their balance controlling statocysts. Movement pattern and social behavior vary greatly among individuals; and (7) Feeding starts in Stage 3, when the mouthparts and the gastric mill are fully developed. Onset of feeding is innate and does not require maternal contributions. In vitro culture of the isogenic marbled crayfish is recommended for broader use in research because it enables not only time and stage‐specific sampling but also precisely timed experimental manipulations. J. Morphol., 2008. © 2008 Wiley‐Liss, Inc.
Activation of microglia by endotoxin suppresses the secretion of glial cell line–derived neurotrophic factor (GDNF) through the action of protein kinase Cα (PKCα) and mitogen‐activated protein kinases (MAPKS)
Authors: Matsushita Yuichi , Nakajima Kazuyuki , Tohyama Yoko , Kurihara Tadashi , Kohsaka Shinichi
Published: April 2008

The ability of microglia to produce/secrete glial cell line–derived neurotrophic factor (GDNF) in vitro was examined. Immunoblotting analysis revealed that nonstimulated microglia release limited amounts of GDNF with molecular sizes of 14 and 17 kDa. However, the secreted amounts significantly decreased when the microglia were activated with the endotoxin lipopolysaccharide (LPS). Comparison of the amounts of GDNF in the cells and the conditioned medium between the nonstimulated microglia and LPS‐stimulated microglia clarified that the secretion of GDNF, but not its production, is strongly suppressed when the microglia are activated with LPS. The inhibitor experiments suggested that the GDNF secretion is depressed by a signaling cascade associated with protein kinase C alpha (PKCα) and/or mitogen‐activated protein kinases (MAPKs). As expected from the above results, a PKC activator suppressed the secretion of GDNF in nonstimulated microglia. Taken together, these results demonstrated that microglia have the ability to produce and secrete GDNF in vitro, and that the secretion is suppressed by stimulation with endotoxin, probably due to a signaling mechanism involving PKCα and/or MAPKs. © 2008 Wiley‐Liss, Inc.
Dynamics of the inflammatory response after murine spinal cord injury revealed by flow cytometry
Authors: Stirling David P. , Yong V. Wee
Published: April 2008

Spinal cord injury (SCI) triggers a robust inflammatory response that contributes in part to the secondary degeneration of spared tissue. Here, we use flow cytometry to quantify the inflammatory response after SCI. Besides its objective evaluation, flow cytometry allows for levels of particular markers to be documented that further aid in the identification of cellular subsets. Analyses of blood from SCI mice for CD45 (common leukocyte antigen), CD11b (complement receptor‐3), Gr‐1 (neutrophil/monocyte marker), and CD3 (T‐cell marker) revealed a marked increase in circulating neutrophils (CD45high:Gr‐1high) at 12 hr compared with controls. Monocyte density in blood increased at 24 hr, and in contrast, lymphocyte numbers were significantly decreased. Mirroring the early increase in neutrophils within the blood, flow analysis of the spinal cord lesion site revealed a significant (P < 0.01) and maintained increase in blood‐derived leukocytes (CD45high:CD11bhigh) from 12 to 96 hr compared with sham‐injured and naive controls. Importantly, this technique clearly distinguishes blood‐derived neutrophils (CD45:Gr‐1high:F4/80negative) and monocyte/macrophages (CD45high) from resident microglia (CD45low) and revealed that the majority of the blood‐derived infiltrate were neutrophils. Our results highlight an assumed, but previously uncharacterized, marked and transient increase in leukocyte populations in blood early after SCI followed by the orchestrated invasion of neutrophils and monocytes into the injured cord. In contrast to mobilization of neutrophils, SCI induces lymphopenia that may contribute negatively to the overall outcome after spinal cord trauma. © 2008 Wiley‐Liss, Inc.
Calcium receptor expression and function in oligodendrocyte commitment and lineage progression: Potential impact on reduced myelin basic protein in CaR‐null mice
Authors: Chattopadhyay Naibedya , Espinosa‐Jeffrey Araceli , Tfelt‐Hansen Jacob , Yano Shozo , Bandyopadhyay Sanghamitra , Brown Edward M. , de Vellis Jean
Published: April 2008

Oligodendrocytes develop from oligodendrocyte progenitor cells (OPCs), which in turn arise from a subset of neuroepithelial precursor cells during midneurogenesis. Development of the oligodendrocyte lineage involves a plethora of cell‐intrinsic and ‐extrinsic signals. A cell surface calcium‐sensing receptor (CaR) has been shown to be functionally expressed in immature oligodendrocytes. Here, we investigated the expression and function of the CaR during oligodendrocyte development. We show that the order of CaR mRNA expression as assessed by quantitative polymerase chain reaction is mature oligodendrocyte > neuron > astrocyte. We next determined the rank order of CaR expression on inducing specification of neural stem cells to the neuronal, oligodendroglial, or astrocytic lineages and found that the relative levels of CaR mRNA expression are OPC > neuron > astrocytes. CaR mRNA expression in cells at various stages of development along the oligodendrocyte lineage revealed that its expression is robustly up‐regulated during the OPC stage and remains high until the premyelinating stage, decreasing thereafter by severalfold in the mature oligodendrocyte. In OPCs, high Ca2+ acting via the CaR promotes cellular proliferation. We further observed that high Ca2+ stimulates the mRNA levels of myelin basic protein in preoligodendrocytes, which is also CaR mediated. Finally, myelin basic protein levels were significantly reduced in the cerebellum of CaR‐null mice during development. Our results show that CaR expression is up‐regulated when neural stem cells are specified to the oligodendrocyte lineage and that activation of the receptor results in OPC expansion and differentiation. We conclude that the CaR may be a novel regulator of oligodendroglial development and function. © 2008 Wiley‐Liss, Inc.
Amyloid β peptide toxicity in differentiated PC12 cells: Calpain‐calpastatin, caspase, and membrane damage
Authors: Vaisid Tali , Kosower Nechama S. , Elkind Esther , Barnoy Sivia
Published: April 2008

Amyloid β peptide (Aβ) is implicated in the pathogenesis of Alzheimer's disease (AD). The peptide is toxic to neurons, possibly by causing initial synaptic dysfunction and neuronal membrane dystrophy, promoted by increased cellular Ca2+. Calpain (Ca2+‐dependent protease) and caspase have also been implicated in AD. There is little information on communication between the two proteases or on the involvement of calpastatin (the specific calpain inhibitor) in Aβ toxicity. We studied the effects of Aβ25–35 (sAβ) on calpain, calpastatin, and caspase in neuronal‐like differentiated PC12 cells. sAβ‐treated cells exhibited primarily cell membrane damage (varicosities along neurites, enhanced membrane permeability to propidium iodide, without apparent nuclear changes of apoptosis, and little poly (ADP‐ribose) polymerase [PARP] degradation). The sAβ‐induced membrane damage is in contrast with staurosporine‐induced damage (nuclear apoptotic changes, PARP degradation, without membrane propidium iodide permeability). sAβ led to activation of caspase‐8 and calpain, promotion of calpastatin degradation (by caspase‐8 and by calpain), and enhanced degradation of fodrin (mainly by calpain). The results support the idea that Aβ causes primarily neuronal membrane dysfunction, and point to cross‐talk between calpain and caspase (protease activation and degradation of calpastatin) in Aβ toxicity. Increased expression of calpastatin and/or decrease in calpain and caspase‐8 may serve as means for ameliorating early symptoms of AD. © 2008 Wiley‐Liss, Inc.
Feedback acceptance in developmental assessment centers: the role of feedback message, participant personality, and affective response to the feedback session
Authors: Bell Suzanne T. , Arthur Winfred
Published: April 2008

We investigated feedback acceptance by participants (N = 141) in an operational developmental assessment center (AC). Consistent with predictions based on self‐enhancement theory and the Affective Infusion Model, results indicated that higher assessor ratings were associated with higher feedback acceptance, and this relationship was partially mediated by the participant's affective reaction to the feedback session. Participants' self‐ratings of their AC performance did not affect this relationship suggesting no support for our prediction based on self‐verification theory. We also investigated the role of participants' self‐ratings of agreeableness, extraversion, and emotional stability in feedback acceptance by testing specific moderated mediation hypotheses. Extraversion was related to feedback acceptance through the affective reaction to the feedback session. Agreeableness moderated the affective reaction to the feedback session and feedback acceptance relationship such that there was a strong relationship between affective reaction and feedback acceptance for highly agreeable participants, but no relationship for low agreeable individuals. For low agreeable individuals, there was a positive direct relationship between the assessor ratings and feedback acceptance which was not observed for highly agreeable individuals. The hypothesized role of emotional stability in predicting feedback acceptance was not supported. Implications for the delivery of feedback in developmental ACs are discussed in light of these findings. Copyright © 2008 John Wiley & Sons, Ltd.
Long work hours: a social identity perspective on meta‐analysis data
Authors: Ng Thomas W. H. , Feldman Daniel C.
Published: April 2008

The current study utilizes social identity theory to investigate employees' work hours. Specifically, we use meta‐analysis to examine the relationships between hours worked and indicators of organizational identity (e.g., organizational support and tenure), occupational identity (e.g., human capital investments and work centrality), and family identity (e.g., family responsibilities and family satisfaction). The meta‐analysis also allowed us to explore other important correlates of hours worked (e.g., situational demands, job performance, mental health, and physical health), moderating variables (e.g., age, gender, and job complexity), and curvilinear relationships of work hours to social identity indicators. Overall, we found that occupational factors and situational demands had the strongest relationships with hours worked, hours worked were negatively associated with measures of employee well‐being, gender had several significant moderating effects, and there were curvilinear relationships between hours worked and well‐being and work–family conflict variables. The article concludes with directions for future theoretical and empirical research. Copyright © 2008 John Wiley & Sons, Ltd.
Team conflict management and team effectiveness: the effects of task interdependence and team identification
Authors: Somech Anit , Desivilya Helena Syna , Lidogoster Helena
Published: April 2008

The present study explores the dynamics of conflict management as a team phenomenon. The study examines how the input variable of task structure (task interdependence) is related to team conflict management style (cooperative versus competitive) and to team performance, and how team identity moderates these relationships. Seventy‐seven intact work teams from high‐technology companies participated in the study. Results revealed that at high levels of team identity, task interdependence was positively associated with the cooperative style of conflict management, which in turn fostered team performance. Although a negative association was found between competitive style and team performance, this style of team conflict management did not mediate between the interactive effect of task interdependence and team identity on team performance. Copyright © 2008 John Wiley & Sons, Ltd.
Analytical methodologies for quantification of ferulic acid and its oligomers
Authors: Barberousse Hélène , Roiseux Olivier , Robert Christelle , Paquot Michel , Deroanne Claude , Blecker Christophe
Published: April 2008

Ferulic acid (4‐hydroxy‐3‐methoxycinnamic acid) is the most widespread hydroxycinnamic acid in the plant world, where it is a key molecule in cell wall architecture. Owing to its high antioxidant properties, ferulic acid shows large potential applications in food industry as well as in the health and cosmetic markets. There is thus a high interest in extracting this high‐value compound from waste materials of the agricultural industry, which requires the selection of an appropriate quantification method. This paper therefore gives an overview of analytical methodologies developed over past decades for quantification of ferulic acid and its oligomers. Copyright © 2008 Society of Chemical Industry
Impact of column temperature and mobile phase components on selectivity of hydrophilic interaction chromatography (HILIC)
Authors: Hao Zhigang , Xiao Baiming , Weng Naidong
Published: April 2008

The retention mechanism and chromatographic behavior for different polar analytes under hydrophilic interaction chromatography (HILIC) conditions have been studied by application of different mobile phases and stationary phases to various analytes at different temperatures. In addition to the commonly accepted mechanism of analyte liquid‐liquid partitioning between mobile phase and water‐enriched solvent layer which is partially immobilized onto the surface of the stationary phase, hydrogen‐bonding, hydrophobic interaction, and ion‐exchange interactions may also be involved. The predominant retention mechanism in HILIC separation is not always easily predictable. It can depend not only on the characteristics of the analytes but also on the selection of mobile and stationary phase compositions. The objective of this review is to evaluate the potential application of column temperature and mobile phase composition toward improving HILIC selectivity. The functional groups from analyte structures, stationary phase materials and organic mobile phase solvents will be highlighted.
Profiling of N‐ and O‐glycopeptides of erythropoietin by capillary zwitterionic type of hydrophilic interaction chromatography/electrospray ionization mass spectrometry
Authors: Takegawa Yasuhiro , Ito Hiroki , Keira Takuro , Deguchi Kisaburo , Nakagawa Hiroaki , Nishimura Shin‐Ichiro
Published: April 2008

Capillary zwitterionic‐type hydrophilic interaction chromatography (ZIC‐HILIC)/ESI‐MS has been applied to the Glu‐C digest of recombinant human erythropoietin (rhEPO) expressed in Chinese hamster ovary (CHO) cells. N‐Glycopeptides (105) and O‐glycopeptides (8) were detected in a single run of the capillary ZIC‐HILIC/ESI‐MS analysis. Among them, N‐acetyl‐neuraminic acids (Neu5Ac) of N‐ and O‐glycans were partially acetylated and some were replaced with N‐glycoyl‐neuraminic acid (Neu5Gc). Their retentions in the ZIC‐HILIC separation can be explained to some extent with the degree of acetylation and N‐glycoylation, both of which influence the hydrophilicity/hydrophobicity of the N‐ and O‐glycan moieties of glycopeptides.
The discovery of antiviral agents: Ten different compounds, ten different stories
Authors: De Clercq Erik
Published: April 2008

This review article, while autobiographical to some extent, describes the discovery of ten (classes of) antiviral compounds that have made (or just did not make) it to the market for the therapy of viral infections, but each in its own way influenced the landscape of our dealing with virus infections: (i) valaciclovir, (ii) BVDU, (iii) DHPA, (iv) cidofovir, (v) adefovir, (vi) tenofovir, (vii) stavudine, (viii) HEPT, (ix) TIBO, and (x) AMD3100. Successful drug development, as is certainly true for antiviral drugs and exemplified for the acyclic nucleoside phosphonates cidofovir, adefovir and tenofovir, requires patience and perseverance, and a close continuous and dedicated interaction between Chemistry, Biology/Medicine and Industry. © 2008 Wiley Periodicals, Inc. Med Res Rev, 28, No. 6, 929–953, 2008
Expression of selenium‐binding protein 1 characterizes intestinal cell maturation and predicts survival for patients with colorectal cancer
Authors: Li Tianhong , Yang Wancai , Li Maomi , Byun Do‐Sun , Tong Chang , Nasser Shannon , Zhuang Min , Arango Diego , Mariadason John M. , Augenlicht Leonard H.
Published: April 2008

To identify candidate genes involved in the development of colorectal cancer, we used cDNA microarrays to analyze gene expression differences between human colorectal tumors and paired adjacent normal mucosa. We identified ∼︁3.5‐fold significant downregulation of selenium‐binding protein 1 (SBP1) in colorectal tumors compared to normal mucosa (p = 0.003). Importantly, stage III colorectal cancer patients with low tumor‐SBP1 expression had significantly shorter disease‐free and overall survival as compared with those patients with high tumor‐SBP1 expression (p = 0.04 and 0.03, respectively). We further characterized the role of SBP1 in colorectal cancer in vivo and in vitro. In normal tissue, SBP1 was maximally expressed in terminally differentiated epithelial cells on the luminal surface of crypts in the large intestine. Consistent with this in vivo localization, SBP1 was upregulated during in vitro colonic cell differentiation along the absorptive (Caco‐2) and secretory (HT29 Clones 16E and 19A) cell lineages. Downregulation (approximately 50%) of SBP1 expression by small interfering RNA in colonic cancer cells was associated with reduced expression of another epithelial differentiation marker, carcinoembryonic antigen (CEA), although PCNA and p21WAF1/cip1 expression were not altered. These data demonstrate that higher expression of SBP1 is associated with differentiation of the normal colonic epithelia and may be a positive prognostic factor for survival in stage III colorectal carcinoma.
Tannin 1‐α‐O‐galloylpunicalagin induces the calcium‐dependent activation of endothelial nitric‐oxide synthase via the phosphatidylinositol 3‐kinase/Akt pathway in endothelial cells
Authors: Chen Lih‐Geeng , Liu Yen‐Chin , Hsieh Chia‐Wen , Liao Being‐Chyuan , Wung Being‐Sun
Published: April 2008

Many polyphenols have been found to increase endothelial nitric oxide (NO) production. In our present study, we investigated the effects of 1‐α‐O‐galloylpunicalagin upon endothelial nitric oxide synthase (eNOS) activity in endothelial cells (ECs). Both 1‐α‐O‐galloylpunicalagin and punicalagin induced NO production in a dose‐dependent manner in ECs. Despite having similar chemical structures, punicalagin induced lower levels of NO production than 1‐α‐O‐galloylpunicalagin. After 1‐α‐O‐galloylpunicalagin addition, a rise in the intracellular Ca2+ concentration preceded NO production. The Ca2+ ionophore A23187 stimulated eNOS phosphorylation and augmented NO production. Pretreatment with Ca2+ chelators inhibited 1‐α‐O‐galloylpunicalagin‐induced eNOS phosphorylation and NO production. Treatment with 1‐α‐O‐galloylpunicalagin did not alter the eNOS protein levels but, unlike punicalagin, induced a sustained activation of eNOS Ser1179 phosphorylation. 1‐α‐O‐galloylpunicalagin was also found to activate ERK1/2, JNK and Akt in ECs. Moreover, simultaneous treatment of these cells with specific phosphatidylinositol‐3‐kinase inhibitors significantly inhibited the observed increases in eNOS activity and phosphorylation levels. In contrast, the inhibition of (ERK)1/2, JNK and p38 had no influence on eNOS Ser1179 phosphorylation. Our present results thus indicate that the 1‐α‐O‐galloylpunicalagin‐induced calcium‐dependent activation of eNOS is primarily mediated via a phosphatidylinositol 3‐kinase/Akt‐dependent increase in eNOS activity, and occurs independently of the eNOS protein content.
Geraniin‐mediated apoptosis by cleavage of focal adhesion kinase through up‐regulation of Fas ligand expression in human melanoma cells
Authors: Lee Jang‐Chang , Tsai Chih‐Yen , Kao Jung‐Yie , Kao Ming‐Ching , Tsai Shih‐Chang , Chang Chih‐Shiang , Huang Li‐Jiau , Kuo Sheng‐Chu , Lin Jen‐Kun , Way Tzong‐Der
Published: April 2008

Geraniin, a form of tannin separated from geranium, causes cell death through induction of apoptosis; however, cell death characteristics for geraniin have not yet been elucidated. Here, we investigated the mechanism of geraniin‐induced apoptosis in human melanoma cells and demonstrated that geraniin was able to induce cell apoptosis in a concentration‐ and time‐dependent manner. We also examined the signaling pathway related to geraniin‐induced apoptosis. To clarify the relationship between focal adhesion kinase (FAK) and geraniin‐induced apoptosis, we treated human melanoma cells with geraniin and found that this resulted dose‐ and time‐dependent degradation in FAK. However, FAK cleavage was significantly inhibited when cells were pretreated with a selective inhibitor of caspase‐3 (Ac‐Asp‐Glu‐Val‐Asp‐CHO). Here, we demonstrated for the first time that geraniin triggered cell death by caspase‐3‐mediated cleavage of FAK. There were two possible mechanisms for activating caspase‐3, mitochondria‐mediated and receptor‐mediated apoptosis. To confirm the geraniin‐relevant signaling pathway, using immunoblot analysis we found that geraniin‐induced apoptosis was associated with the up‐regulation of Fas ligand expression, the activation of caspase‐8, the cleavage of Bid, and the induction of cytochrome c release from mitochondria to the cytosol. Treatment with geraniin caused induction of caspase‐3 activity in a dose‐ and time‐dependent manner followed by proteolytic cleavage of poly‐(ADP‐ribose) polymerase, and DNA fragmentation factor 45. The geraniin‐induced apoptosis may provide a pivotal mechanism for its cancer‐chemopreventive action.
White‐light emission from mixing blue and red‐emitting metal complexes
Authors: Shunmugam Raja , Tew Gregory N.
Published: April 2008

Combining polymeric architectures with metal ions produces hybrid materials with extremely rich properties. We have been studying polymers containing terpyridine in the side chain. This report discusses a novel white‐light emission from a two‐emitter system comprising a blue‐emitting dysprosium‐chelated polymer and a red‐emitting ruthenium complex. The polymer architecture easily allows the incorporate of blue color into the material and provides a matrix which leads to the facile production of truly white light. Copyright © 2008 John Wiley & Sons, Ltd.