bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of a physician assistant/hospitalist service in an academic medical center: Impact on efficiency and patient outcomes
Authors: Roy Christopher L. , Liang Catherine L. , Lund Maha , Boyd Catherine , Katz Joel T. , McKean Sylvia , Schnipper Jeffrey L. 
Published: October 2008

AbstractBACKGROUND:Accreditation Council on Graduate Medical Education (ACGME) duty hour restrictions have led to the widespread implementation of non–house staff services in academic medical centers, yet little is known about the quality and efficiency of patient care on such services.OBJECTIVE:To evaluate the quality and efficiency of patient care on a physician assistant/hospitalist service compared with that of traditional house staff services.DESIGN:Retrospective cohort study.SETTING:Inpatient general medicine service of a 747‐bed academic medical center.PATIENTS:A total of 5194 consecutive patients admitted to the general medical service from July 2005 to June 2006, including 992 patients on the physician assistant/hospitalist service and 4202 patients on a traditional house staff service.INTERVENTION:A geographically localized service staffed with physician assistants and supervised by hospitalists.MEASUREMENTS:Length of stay (LOS), cost of care, inpatient mortality, intensive care unit (ICU) transfers, readmissions, and patient satisfaction.RESULTS:Patients admitted to the study service were younger, had lower comorbidity scores, and were more likely to be admitted at night. After adjustment for these and other factors, and for clustering by attending physician, total cost of care was marginally lower on the study service (adjusted costs 3.9% lower; 95% confidence interval [CI] −7.5% to −0.3%), but LOS was not significantly different (adjusted LOS 5.0% higher; 95% CI, −0.4% to +10%) as compared with house staff services. No difference was seen in inpatient mortality, ICU transfers, readmissions, or patient satisfaction.CONCLUSIONS:For general medicine inpatients admitted to an academic medical center, a service staffed by hospitalists and physician assistants can provide a safe alternative to house staff services, with comparable efficiency. Journal of Hospital Medicine 2008;3:361–368. © 2008 Society of Hospital Medicine.
Discharge against medical advice: Ethical considerations and professional obligations
Authors: Berger Jeffrey T. 
Published: October 2008

AbstractDischarges against medical advice (AMA) account for approximately 1% of discharges for general medical patients. Patients discharged AMA have longer eventual hospital stays and worse health outcomes. These patients are also less likely to have an established relationship with a physician, tend to have poorer social supports, and are more likely to abuse alcohol and other substances. These discharges are also distressing for physicians and other health professionals. How should physicians manage their conflicted obligations to respect patients' choices and to prevent harms from befalling their patients? What are physicians' obligations to their patients who leave accepting only partial or inadequate treatment plans or no treatment at all? When should physicians question the decision‐making capacity of patients who make dangerous judgments to leave the hospital? This article examines the ethical and professional implications of discharge AMA. Journal of Hospital Medicine 2008;3:403–408. © 2008 Society of Hospital Medicine.
Survey of the year 2007 commercial optical biosensor literature
Authors: Rich Rebecca L. , Myszka David G. 
Published: October 2008

AbstractIn 2007, 1179 papers were published that involved the application of optical biosensors. Reported developments in instrument hardware, assay design, and immobilization chemistry continue to improve the technology's throughput, sensitivity, and utility. Compared to recent years, the widest range of platforms, both traditional format and array‐based, were used. However, as in the past, we found a disappointingly low percentage of well‐executed experiments and thoughtful data interpretation. We are alarmed by the high frequency of suboptimal data and over‐interpreted results in the literature. Fortunately, learning to visually recognize good—and more importantly, bad—data is easy. Using examples from the literature, we outline several features of biosensor responses that indicate experimental artifacts versus actual binding events. Our goal is to have everyone, from benchtop scientists to project managers and manuscript reviewers, become astute judges of biosensor results using nothing more than their eyes. Copyright © 2008 John Wiley & Sons, Ltd.
Spatially patterned gene expression for guided neurite extension
Authors: Houchin‐Ray Tiffany , Huang Alyssa , West Erin R. , Zelivyanskaya Marina , Shea Lonnie D. 
Published: October 2008

AbstractAxon pathfinding by localized expression of guidance molecules is critical for the proper development of the nervous system. In this report, we present a well‐defined spatially patterned gene expression system to investigate neurite guidance in vitro. Nonviral gene delivery was patterned by combining substrate‐mediated gene delivery with soft lithography techniques, and the amount of protein produced at the region of localized expression was varied by altering the vector concentration and the width of the pattern, highlighting the flexibility of the system. A neuronal coculture model was used to investigate responses to spatial patterns of nerve growth factor (NGF) expression. The soluble NGF gradient elicited a guidance cue, and the degree of guidance was governed by the distance a neuron was cultured from the pattern and the time between accessory cell and neuron seedings. A portion of the diffusible NGF bound to the culture surface in the extracellular space, and the surface‐associated NGF supported neuron survival and neurite outgrowth. However, the surface‐bound NGF gradient alone did not elicit a guidance signal, and in fact masked the guidance cue by soluble NGF gradients. Mathematical modeling of NGF diffusion was used to predict the concentration gradients, and both the absolute and fractional gradients capable of guiding neurites produced by patterned gene expression differed substantially from the values obtained with existing engineered protein gradients. Spatially patterned gene expression provides a versatile tool to investigate the factors that may promote neurite guidance. © 2008 Wiley‐Liss, Inc.
Histone deacetylase activity in conjunction with E2F‐1 and p53 regulates Apaf‐1 expression in 661W cells and the retina
Authors: Wallace Deborah M. , Cotter Thomas G. 
Published: October 2008

AbstractApaf‐1 and the cysteine proteases known as caspases are genes central to the intrinsic apoptotic pathway in the retina. Previously, we have shown that histone deacetylase (HDAC) activity regulates Apaf‐1 expression in the retina. In this study, we unravel the detailed molecular mechanism of HDAC‐mediated regulation of Apaf‐1 initially by use of a cell line (661W), which expresses some cone‐specific genes and then by means of an ex vivo retinal explant system. Inhibition of HDAC activity by trichostatin A (TSA) up‐regulates Apaf‐1 expression, which precedes the induction of apoptosis. Furthermore, by a bioinformatics approach, we identify E2F‐1 and p53 binding sites on the mouse Apaf‐1 promoter and show by chromatin immunoprecipitation assays that these sites are occupied in vitro and that treatment with TSA results in increased binding of E2F‐1 and p53 to the Apaf‐1 promoter. By performing siRNA to these transcription factors, we illustrate that they govern Apaf‐1 expression levels in vitro. Finally, in a retinal explant system, we show that similar to our 661W results, E2F‐1 and p53 are up‐regulated after inhibition of HDAC activity in the retina. This correlates with our previous observation in the explant system that Apaf‐1 expression increases significantly and leads to an induction of apoptosis after inhibition of HDAC activity. Overall, we propose a role for HDAC activity, E2F‐1, and p53 in the regulation of Apaf‐1 expression in 661W cells; initial data also indicate a regulatory role in the retina. © 2008 Wiley‐Liss, Inc.
Immunocytochemical expression of dopamine‐related transcription factors Pitx3 and Nurr1 in prenatally stressed adult rats
Authors: Katunar Maria R. , Saez Trinidad , Brusco Alicia , Antonelli Marta C. 
Published: October 2008

AbstractRats exposed to different types of stress during the last week of pregnancy produce offspring that show severe anomalies in neural development and brain morphology. We have previously reported that prenatal stress (PS) induced by immobilization increases D2‐type dopamine (DA) receptor levels in the adult offspring, with a concomitant reduction in DA release in prefrontal cortex after amphetamine stimulation. Recently, two transcription factors, Nurr1 and Pitx3, have been identified that are expressed at critical moments of DA neuron differentiation. Their genetic expression is activated immediately after these neuron determinations and maintained through adult life. Nurr1 regulates several proteins that are required for dopamine synthesis and regulation, and Pitx3 is specifically involved in the terminal differentiation and maintenance of dopamine neurons. By means of an immunocytochemistry approach, we studied the expression of Nurr1 and found an ubiquitous distribution in cerebral cortex, hippocampus, thalamus, amygdala, and midbrain, whereas Pitx3 remains restricted to the mesencephalic DA neurons such as substantia nigra and ventral tegmental area. Our results show that the expression of both Nurr1 and Pitx3 increased in prenatally stressed adult offspring in the ventral tegmental area, whereas no changes were observed in the substantia nigra area. It might be hypothesized that the increase of the specific dopaminergic transcription factors might be a compensatory mechanism to counteract the reduction in dopamine levels previously observed as a consequence of prenatal stress. © 2008 Wiley‐Liss, Inc.
Innate and adaptive immune activation in the brain of MPS IIIB mouse model
Authors: DiRosario Julianne , Divers Erin , Wang Chuansong , Etter Jonathan , Charrier Alyssa , Jukkola Peter , Auer Herbert , Best Victoria , Newsom David L. , McCarty Douglas M. , Fu Haiyan 
Published: October 2008

AbstractMucopolysaccharidosis (MPS) IIIB is a lysosomal storage disease with severe neurological manifestations due to α‐N‐acetylglucosaminidase (NaGlu) deficiency. The mechanism of neuropathology in MPS IIIB is unclear. This study investigates the role of immune responses in neurological disease of MPS IIIB in mice. By means of gene expression microarrays and real‐time quantitative reverse transcriptase–polymerase chain reaction, we demonstrated significant up‐regulation of numerous immune‐related genes in MPS IIIB mouse brain involving a broad range of immune cells and molecules, including T cells, B cells, microglia/macrophages, complement, major histocompatibility complex class I, immunoglobulin, Toll‐like receptors, and molecules essential for antigen presentation. The significantly enlarged spleen and lymph nodes in MPS IIIB mice were due to an increase in splenocytes/lymphocytes, and functional assays indicated that the T cells were activated. An autoimmune component to the disease was further suggested by the presence of putative autoantigen or autoantigens in brain extracts that reacted specifically with serum IgG from MPS IIIB mice. We also demonstrated for the first time that immunosuppression with prednisolone alone can significantly slow the central nervous system disease progression. Our data indicate that immune responses contribute greatly to the neuropathology of MPS IIIB and should be considered as an adjunct treatment in future therapeutic developments for optimal therapeutic effect. © 2008 Wiley‐Liss, Inc.
Spinal cord dysmyelination caused by an antiproteolipid protein IgM antibody: Implications for the mechanism of central nervous system myelin formation
Authors: Rosenbluth J. , Schiff R. 
Published: October 2008

AbstractAntiglycolipid IgM antibodies are known to induce formation of “wide spaced” or “expanded” myelin, a distinctive form of dysmyelination characterized by a repeat period approximately two or three times normal, which is seen also in diseases, including multiple sclerosis. To determine whether an antibody directed against a myelin protein would cause equivalent pathology, we implanted O10 hybridoma cells into the spinal cord of adult or juvenile rats. O10 produces an IgM directed against PLP, the major protein of CNS myelin. Subsequent examination of the cords showed focal demyelination and remyelination. In addition, however, some juvenile cords, but none of the adult cords, displayed wide‐spaced myelin with lamellae separated by an extracellular material comprising elements consistent with IgM molecules in appearance. Wide spacing tended to involve the outer layers of the sheath and in some cases alternated with normally spaced lamellae. A feature not seen previously consists of multiple expanded myelin lamellae in one sector of a sheath continuous with normally spaced lamellae in another, resulting in variation in sheath thickness around the axonal circumference. This uneven distribution of wide‐spaced lamellae is most simply explained based on incorporation of IgM molecules into immature sheaths during myelin formation and implies a model of CNS myelinogenesis more complex than simple spiraling. The periaxonal space never displays widening of this kind, but the interface with adjacent myelin sheaths or oligodendrocytes may. Thus, wide spacing appears to require that IgM molecules bridge between two PLP‐containing membranes and does not reflect the mere presence of immunoglobulin within the extracellular space. © 2008 Wiley‐Liss, Inc.
AMPA receptor‐mediated cell death is reduced by docosahexaenoic acid but not by eicosapentaenoic acid in area CA1 of hippocampal slice cultures
Authors: Ménard Caroline , Patenaude Christian , Gagné Anne‐Marie , Massicotte Guy 
Published: October 2008

AbstractOver the last decade, several studies have shown that high levels of polyunsaturated fatty acids (PUFAs) in the brain might limit neuronal damage in various pathological conditions. For example, in animal models of Alzheimer's disease, omega‐3 type PUFAs such as docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids have been proposed to decrease both the cognitive and the cellular manifestations of premature ageing. The mechanisms by which they promote brain integrity remain to be established, and the experiments on cultured hippocampal slices described here examine the possibility that omega‐3 fatty acids can modulate brain cell viability by interacting with glutamate receptors. We observed, by lactate dehydrogenase release and propidium iodide (PI) uptake, that excitotoxicity triggered by an alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) receptor agonist was markedly reduced in hippocampal slices treated with DHA. PI uptake experiments also revealed that neuroprotection by DHA was restricted to the hippocampal CA1 region and could not be reproduced by EPA or arachidonic acid, an omega‐6 PUFA. Moreover, the beneficial effect of DHA was specific to AMPA receptor stimulation, insofar as the toxicity induced by N‐methyl‐D‐aspartate or kainate receptor agonists was not diminished by DHA preincubation. Biotinylation experiments finally indicated that the neuroprotective actions of DHA could result from down‐regulation of AMPA receptors in hippocampal membranes. This investigation thus provides the first indication that a beneficial outcome of DHA on the brain could derive from specific modulation of AMPA‐mediated toxicity, reinforcing the notion that dietary DHA uptake might be useful in preventing neurodegenerative diseases. © 2008 Wiley‐Liss, Inc.
Cyclophilin D is expressed predominantly in mitochondria of γ‐aminobutyric acidergic interneurons
Authors: Hazelton Julie L. , Petrasheuskaya Maryna , Fiskum Gary , Kristián Tibor 
Published: October 2008

AbstractBrain mitochondria are relatively resistant to calcium‐induced mitochondrial permeability transition (MPT), with heterogenic response to the insult. The cause for this heterogeneity is not clear, so we studied the distribution of a key regulator of the MPT, cyclophilin D (cypD), within the rat brain by using immunohistology and Western blotting. Motor and parietal cortex, hippocampus, striatum, substantia nigra, ventral tegmental area, septum, and mammillary nucleus displayed a strong immunoreactivity to cypD within specific subpopulation of neurons. The staining was punctate and intense, particularly in perinuclear regions of cells. Apart from neurons, a subpopulation of astrocytes and NG2‐positive cells showed higher cypD immunoreactivity. Double staining of cypD with cytochrome oxidase confirmed the mitochondrial specificity of cypD immunoreactivity. The neurons with high levels of cypD also expressed glutamate decarboxylase (GAD) and the calcium binding protein parvalbumin or calbinding D‐28k, identifying these cells as interneurons. Western blots confirmed our immunohistochemical findings, showing significantly higher levels of cypD in crude mitochondria of substantia nigra compared with cortex or striatum. Furthermore, nonsynaptic mitochondria representing mainly mitochondria from cell bodies of neurons and glia have about 16% higher levels of cypD compared with synaptic mitochondria that are localized in presynaptic buttons. These data suggest that the underlying factor of heterogenic response of isolated brain mitochondria to MPT‐inducing insults can be the different expression levels of cypD, with mitochondria originated from interneurons as the most sensitive. © 2008 Wiley‐Liss, Inc.
Characterization of CD8‐positive macrophages infiltrating the central nervous system of rats with chronic autoimmune encephalomyelitis
Authors: Hiraki Keiko , Park Il‐Kwon , Kohyama Kuniko , Matsumoto Yoh 
Published: October 2008

AbstractCD8+ macrophages appear in the central nervous system (CNS) under various pathological conditions such as trauma and ischemia. Furthermore, macrophages expressing CD8 were found in CNS lesions of chronic, but not acute, experimental autoimmune encephalomyelitis (EAE). To further characterize cells with this phenotype, we examined CD8+ macrophages/monocytes in the CNS and peripheral organs during the course of acute and chronic EAE that had been induced by immunization of rats with myelin basic protein and myelin oligodendrocyte glycoprotein, respectively. Counting CD8+ macrophages in CNS lesions revealed that their numbers increased reaching about 60% of total infiltrating macrophages in chronic EAE, while CD8+ macrophages remained less than 5% throughout the course of acute EAE. Unexpectedly, however, higher abundance of CD8+ monocytes/macrophages in the peripheral blood was found in both acute and chronic EAE. Real‐time polymerase chain reaction analysis revealed no significant difference in the levels of chemokines and chemokine receptors of blood CD8+ monocytes between acute and chronic EAE. mRNA expression of perforin, a cytotoxic substance, was up‐regulated in CD8+ monocytes compared with that of CD8− monocytes in both acute and chronic EAE. These findings suggest that activated CD8+ macrophages may play a cytotoxic role in chronic EAE lesions and that cells other than CD8+ monocytes/macrophages determined the difference in CNS pathology between acute and chronic EAE. Analysis of CD8+ monocytes/macrophages may provide useful information to permit further dissect the pathomechanisms of multiple sclerosis and to develop effective immunotherapies against autoimmune diseases in the CNS. © 2008 Wiley‐Liss, Inc.
Intensity of chronic cerebral hypoperfusion determines white/gray matter injury and cognitive/motor dysfunction in mice
Authors: Miki Kazunori , Ishibashi Satoru , Sun Liyuan , Xu Haiyan , Ohashi Wataru , Kuroiwa Toshihiko , Mizusawa Hidehiro 
Published: October 2008

AbstractWe sought to establish a mouse model of subcortical ischemic vascular dementia (SIVD) that develops predominant white matter (WM) injury and cognitive dysfunction induced by chronic cerebral hypoperfusion. Adult C57Bl/6 male (n = 48) mice were subjected to bilateral common carotid artery stenosis with external microcoils (inner diameters: 0.16 mm, left; 0.18 mm, right). Mice were categorized according to left‐side cerebral blood flow (CBF) value on day 6 into those with severe cerebral hypoperfusion (SCH; n = 16, < 30% of preoperative CBF baseline value) or moderate cerebral hypoperfusion (MCH; n = 21, 30–50% of preoperative value). Another 15 mice were sham operated. Neurological dysfunction was evaluated by Morris water maze, rotating rod, and open field tests. Histopathological examination was performed on day 35 after surgery. MCH animals showed persistent hyperlocomotion with reduced anxiety and spatial reference memory dysfunction. Rarefaction and small necrotic lesions were predominantly confined to the WM, with reactive astrocytosis, microglial infiltration, axonal loss, and myelin disruption, and these changes were dominant on the left side. SCH animals had persistent hyperlocomotion and motor dysfunction, and their ischemic lesions extended from the WM to the hippocampus and cortex. In MCH animals, myelin basic protein and neurofilament fiber densities in the WM were correlated with the time spent in the correct area in the water maze probe trials. Our MCH mouse model with the development of several types of neurological dysfunction with high reproducibility would be useful for investigating the pathomechanisms of WM injury in human SIVD. © 2008 Wiley‐Liss, Inc.
Determinants and performance effects of the allocation of ownership rights in consulting firms
Authors: Richter Ansgar , Schröder Katrin 
Published: October 2008

AbstractThis paper provides a joint assessment of the antecedents and the performance consequences of the allocation of ownership rights in professional service firms (PSFs). Drawing on established economic theory, we argue that the efficiency implications of alternative ownership arrangements drive the allocation of ownership rights. We test our arguments using a sample of 119 large and medium‐sized consulting firms. The results confirm the significance of capital requirements, service standardization, business risk, and organization size as determinants of the allocation of ownership rights in these firms. We do not find ownership allocationper seto be a significant driver of performance. The results suggest that the optimal allocation of ownership rights is endogenously determined by the conditions under which consulting firms operate. Copyright © 2008 John Wiley & Sons, Ltd.
Designing a frame: rhetorical strategies of architects
Authors: Jones Candace , Livne‐Tarandach Reut 
Published: October 2008

AbstractWe examine the rhetorical strategy of architects in widely available architectural texts, to identify what words are available for use in the cultural register. Our results show that these cultural register texts use distinct but related rhetorics; vocabularies of competency that are revealed through clusters of keywords and which capture institutional logics of business, profession and state. We then examine how architect firms use these keywords as rhetorical strategies when competing for projects from clients. Our results reveal that architect firms deploy multivalent keywords—keywords that bridge institutional logics with the same word having multiple meanings—and combine pragmatically unique keywords from distinct logics, allowing them to appeal to multiple, diverse interests in their audiences. Copyright © 2008 John Wiley & Sons, Ltd.