bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns of Medical and Nursing Staff Communication in Nursing Homes: Implications and Insights From Complexity Science
Authors: Colón-Emeric Cathleen S. , Ammarell Natalie , Bailey Donald , Corazzini Kirsten , Lekan-Rutledge Deborah , Piven Mary L. , Utley-Smith Queen , Anderson Ruth A.
Published: January 2006

Complexity science teaches that relationships among health care providers are key to our understanding of how quality care emerges. The authors sought to compare the effects of differing patterns of medicine-nursing communication on the quality of information flow, cognitive diversity, self-organization, and innovation in nursing homes. Two facilities participated in 6-month case studies using field observations, shadowing, and depth interviews. In one facility, the dominant pattern of communication was a vertical “chain of command” between care providers, characterized by thin connections and limited information exchange. This pattern limited cognitive diversity and innovation in clinical problem solving. The second facility used an open communication pattern between medical and frontline staff. The authors saw higher levels of information flow, cognitive diversity, innovation, and self-organization, although tempered by staff turnover. The patterns of communication between care providers in nursing facilities have an important impact on their ability to provide quality, innovative care.
Dendritic Plasticity in the Adult Neocortex
Authors: Hickmott Peter W. , Ethell Iryna M.
Published: January 2006

Dendrites are a major determinant of how neurons integrate and process incoming information, and thus, they play a vital role in the functional properties of neural circuits. During the past 30 years, it has become clear that the functional organization of the adult neocortex (and other parts of the brain) is dynamic and can change in response to experimental manipulations that affect cortical activity patterns. A variety of changes in the cortical microcircuit, including changes in synaptic function, neuronal membrane properties, and axonal trajectories, are associated with these functional changes. In this review, the authors discuss changes in the structure of dendrites in the adult neocortex, the sorts of experimental manipulations that induce these changes, and some possible molecular mechanisms that may underlie the changes.
Linguistic Profiling
Authors: Squires Gregory D. , Chadwick Jan
Published: January 2006

“Linguistic profiling,” the identification of a person’s race from the sound of their voice and the utilization of that information to discriminate on the basis of race, has been documented in the home rental market. This article examines this phenomenon in the home insurance industry. From an analysis of matched-paired tests conducted by fair-housing organizations, we find that home insurance agents are generally able to detect the race of someone who contacts them by telephone and that this information affects the services provided those who inquire about purchasing a home insurance policy.
Citizens, Accountability, and Service Satisfaction
Authors: Roch Christine H. , Poister Theodore H.
Published: January 2006

Understanding how citizen-consumers form evaluations of public services is critical to understanding account ability in democratic governance. The task of using citizens’ assessments of service quality as an accountability mechanism, however, may be more complex than is commonly understood. In particular, little research has examined how citizens’ expectations about the quality of services may influence their levels of satisfaction with public services. In this article, we examine empirically the relationship between perceived performance, expectations, and satisfaction. We examine these relationships across three service areas: trash, police, and schools, relying on survey data from a statewide survey of Georgia residents. Our results suggest higher subjective assessments of service quality are positively related to satisfaction. They also suggest, however, that an “A” service is not always associated with the same level of satisfaction; holding citizens’ assessments of service quality constant, positive disconfirmation of expectations increases citizen-consumers’ levels of satisfaction with services.
Direct evidence for ex vivo expansion of human hematopoietic stem cells
Authors: Ando Kiyoshi , Yahata Takashi , Sato Tadayuki , Miyatake Hiroko , Matsuzawa Hideyuki , Oki Masayuki , Miyoshi Hiroyuki , Tsuji Takashi , Kato Shunichi , Hotta Tomomitsu
Published: January 2006

To characterize human hematopoietic stem cells (HSCs), xenotransplantation techniques such as the severe combined immunodeficiency (SCID) mouse repopulating cell (SRC) assay have proven the most reliable methods thus far. While SRC quantification by limiting dilution analysis (LDA) is the gold standard for measuring in vitro expansion of human HSCs, LDA is a statistical method and does not directly establish that a single HSC has self-renewed in vitro. This would require a direct clonal method and has not been done. By using lentiviral gene marking and direct intra-bone marrow injection of cultured CD34+ CB cells, we demonstrate here the first direct evidence for self-renewal of individual SRC clones in vitro. Of 74 clones analyzed, 20 clones (27%) divided and repopulated in more than 2 mice after serum-free and stroma-dependent culture. Some of the clones were secondary transplantable. This indicates symmetric self-renewal divisions in vitro. On the other hand, 54 clones (73%) present in only 1 mouse may result from asymmetric divisions in vitro. Our data demonstrate that current ex vivo expansion conditions result in reliable stem cell expansion and the clonal tracking we have employed is the only reliable method that can be used in the development of clinically appropriate expansion methods.
Bone marrow mononuclear cells are recruited to the sites of VEGF-induced neovascularization but are not incorporated into the newly formed vessels
Authors: Zentilin Lorena , Tafuro Sabrina , Zacchigna Serena , Arsic Nikola , Pattarini Lucia , Sinigaglia Milena , Giacca Mauro
Published: January 2006

Vascular endothelial growth factor (VEGF) is a key regulator of blood vessel formation during both vasculogenesis and angiogenesis. The prolonged expression of VEGF in the normoperfused skeletal muscles of adult rodents after gene transfer using AAV vectors induces the formation of a large set of new capillaries and small arteries. Notably, this process is accompanied by the massive infiltration by mononuclear cells. This observation raises the possibility that these cells might represent circulating progenitors that are eventually incorporated in the newly formed vessels. Here we explore this possibility by exploiting 4 different experimental models based on (a) the transplantation of male bone marrow into female recipients; (b) the transplantation of Tie2-GFP transgenic bone marrow; (c) the transplantation of bone marrow in the presence of erythropoietin (EPO), a mobilizer of endothelial progenitor cells (EPCs); and (d) the reimplantation of ex vivo–expanded EPCs. In all 4 models, VEGF acted as a powerful attractor of bone marrow–derived mononuclear cells, bearing different myeloid and endothelial markers proper of the EPCs to the sites of neovascularization. In no case, however, were the attracted cells incorporated in the newly formed vasculature. These observations indicate that new blood vessel formation induced by VEGF occurs through bona fide sprouting angiogenesis; the contribution of the infiltrating bone marrow–derived cells to this process still remains enigmatic.
Thrombin overcomes the thrombosis defect associated with platelet GPVI/FcRγ deficiency
Authors: Mangin Pierre , Yap Cindy L. , Nonne Christelle , Sturgeon Sharelle A. , Goncalves Isaac , Yuan Yuping , Schoenwaelder Simone M. , Wright Christine E. , Lanza Francois , Jackson Shaun P.
Published: January 2006

Fibrillar collagens are among the most potent activators of platelets and play an important role in the initiation of thrombosis. The glycoprotein VI (GPVI)/FcRγ-chain complex is a central collagen receptor and inhibitors of GPVI produce a major defect in arterial thrombogenesis. In this study we have examined arterial thrombus formation in mice lacking the GPVI/FcRγ-chain complex (FcRγ–/–). Using 3 distinct arterial thrombosis models involving deep vascular injury, we demonstrate that deficiency of GPVI/FcRγ is not associated with a major defect in arterial thrombus formation. In contrast, with milder vascular injury deficiency of GPVI/FcRγ was associated with a 30% reduction in thrombus growth. Analysis of FcRγ–/– platelets in vitro, using thrombin-dependent and -independent thrombosis models, demonstrated a major role for thrombin in overcoming the thrombosis defect associated with GPVI/FcRγ deficiency. Inhibition of thrombin in vivo produced a much greater defect in thrombus formation in mice lacking GPVI/FcRγ compared with normal controls. Similarly, thrombin inhibition produced a marked prolongation in bleeding time in FcRγ–/– mice relative to wild-type mice. Our studies define an important role for thrombin in overcoming the hemostatic and thrombotic defect associated with GPVI/FcRγ deficiency. Moreover, they raise the interesting possibility that the full antithrombotic potential of GPVI receptor antagonists may only be realized through the concurrent administration of anticoagulant agents.
Phosphorylation of Gata1 at serine residues 72, 142, and 310 is not essential for hematopoiesis in vivo
Authors: Rooke Heather M. , Orkin Stuart H.
Published: January 2006

Phosphorylation of transcription factors is important in posttranslational control of protein function. The indispensable zinc-finger transcription factor, Gata1, is phosphorylated constitutively at 6 serine residues (26, 49, 72, 142, 178, 187), and at a seventh (310) following induction of erythroid differentiation. However, the biologic consequences of phosphorylation with respect to function are unclear. To address this issue, we generated mice with serine-to-alanine mutations at the inducibly phosphorylated serine 310 alone or at conserved serine residues 72, 142, and 310 together. The peripheral blood parameters of the mice were normal, as was their response to acute erythropoietic stress. Analysis of hematopoietic progenitor populations during ontogeny and into adulthood showed a moderate decrease in erythroid burst-forming unit (BFU-E) and erythroid colony-forming unit (CFU-E) numbers only in the adult bone marrow of the triple mutant. Yet, later stage erythropoiesis was not perturbed. This suggests that any molecular consequences associated with loss of phosphorylation at residues 72, 142, and 310 can be compensated for in the in vivo environment.
Upregulated Genes In Sporadic, Idiopathic Pulmonary Arterial Hypertension
Authors: Edgar Alasdair J , Chacón Matilde R , Bishop Anne E , Yacoub Magdi H , Polak Julia M
Published: January 2006

Background

To elucidate further the pathogenesis of sporadic, idiopathic pulmonary arterial hypertension (IPAH) and identify potential therapeutic avenues, differential gene expression in IPAH was examined by suppression subtractive hybridisation (SSH).

Methods

Peripheral lung samples were obtained immediately after removal from patients undergoing lung transplant for IPAH without familial disease, and control tissues consisted of similarly sampled pieces of donor lungs not utilised during transplantation. Pools of lung mRNA from IPAH cases containing plexiform lesions and normal donor lungs were used to generate the tester and driver cDNA libraries, respectively. A subtracted IPAH cDNA library was made by SSH. Clones isolated from this subtracted library were examined for up regulated expression in IPAH using dot blot arrays of positive colony PCR products using both pooled cDNA libraries as probes. Clones verified as being upregulated were sequenced. For two genes the increase in expression was verified by northern blotting and data analysed using Student's unpaired two-tailed t-test.

Results

We present preliminary findings concerning candidate genes upregulated in IPAH. Twenty-seven upregulated genes were identified out of 192 clones examined. Upregulation in individual cases of IPAH was shown by northern blot for tissue inhibitor of metalloproteinase-3 and decorin (P < 0.01) compared with the housekeeping gene glyceraldehydes-3-phosphate dehydrogenase.

Conclusion

Four of the up regulated genes, magic roundabout, hevin, thrombomodulin and sucrose non-fermenting protein-related kinase-1 are expressed specifically by endothelial cells and one, muscleblind-1, by muscle cells, suggesting that they may be associated with plexiform lesions and hypertrophic arterial wall remodelling, respectively.
Multilocus and interaction-based genome scan for alcoholism risk factors in Caucasian Americans: the COGA study
Authors: Williams Adrienne H , Brown W Mark , Langefeld Carl D
Published: January 2006

In this paper, we applied the nonparametric linkage regression approach to the Caucasian genome scan data from the Collaborative Study on the Genetics of Alcoholism to search for regions of the genome that exhibit evidence for linkage to putative alcoholism-predisposing genes. The multipoint single-locus model identified four regions of the genome with LOD scores greater than one. These regions were on 7p near D7S1790 (LOD = 1.31), two regions on 7q near D7S1870 (LOD = 1.15) and D7S1799 (LOD = 1.13) and 21q near D21S1440 and D21S1446 (LOD = 1.78). Jointly modeling these loci provided stronger evidence for linkage in each of these regions (LOD = 1.58 on 7q11, LOD = 1.61 on 11q23, and LOD = 1.95 on 21q22). The evidence for linkage tended to increase among pedigrees with earlier mean age of onset at 8q23 (p = 0.0016), 14q21 (p = 0.0079), and 18p12 (p = 0.0021) and with later mean age of onset at 4q35 (p = 0.0067) and 9p22 (p = 0.0008).
A Bayesian approach for applying Haseman-Elston methods
Authors: Yoon Seungtai , Suh Young Ju , Mendell Nancy Role , Ye Kenny Qian
Published: January 2006

The main goal of this paper is to couple the Haseman-Elston method with a simple yet effective Bayesian factor-screening approach. This approach selects markers by considering a set of multigenic models that include epistasis effects. The markers are ranked based on their marginal posterior probability. A significant improvement over our previously proposed Bayesian variable selection methodology is a simple Metropolis-Hasting algorithm that requires minimum tuning on the prior settings. The algorithm, however, is also flexible enough for us to easily incorporate our hypotheses and avoid computational pitfalls. We apply our approach to the microsatellite data of Collaborative Studies on Genetics of Alcoholism using the coded values for the ALDX1 variable as our response.
An updated meta-analysis approach for genetic linkage
Authors: Etzel Carol J , Liu Mei , Costello Tracy J
Published: January 2006

We present a meta-analysis procedure for genome-wide linkage studies (MAGS). The MAGS procedure combines genome-wide linkage results across studies with possibly distinct marker maps. We applied the MAGS procedure to the simulated data from the Genetic Analysis Workshop 14 in order to investigate power to detect linkage to disease genes and power to detect linkage to disease modifier genes while controlling for type I error. We analyzed all 100 replicates of the four simulated studies for chromosomes 1 (disease gene), 2 (modifier gene), 3 (disease gene), 4 (no disease gene), 5 (disease gene), and 10 (modifier gene) with knowledge of the simulated disease gene locations. We found that the procedure correctly identified the disease loci on chromosomes 1, 3, and 5 and did not erroneously identify a linkage signal on chromosome 4. The MAGS procedure provided little to no evidence of linkage to the disease modifier genes on chromosomes 2 and 10.
Association between health information, use of protective devices and occurrence of acute health problems in the Prestige oil spill clean-up in Asturias and Cantabria (Spain): a cross-sectional study
Authors: Carrasco José Miguel , Lope Virginia , Pérez-Gómez Beatriz , Aragonés Nuria , Suárez Berta , López-Abente Gonzalo , Rodríguez-Artalejo Fernando , Pollán Marina
Published: January 2006

Background

This paper examines the association between use of protective devices, frequency of acute health problems and health-protection information received by participants engaged in the Prestige oil spill clean-up in Asturias and Cantabria, Spain.

Methods

We studied 133 seamen, 135 bird cleaners, 266 volunteers and 265 paid workers selected by random sampling, stratified by type of worker and number of working days. Information was collected by telephone interview conducted in June 2003. The association of interest was summarized, using odds ratios (OR) obtained from logistic regression.

Results

Health-protection briefing was associated with use of protective devices and clothing. Uninformed subjects registered a significant excess risk of itchy eyes (OR:2.89; 95%CI:1.21–6.90), nausea/vomiting/dizziness (OR:2.25; 95%CI:1.17–4.32) and throat and respiratory problems (OR:2.30; 95%CI:1.15–4.61). There was a noteworthy significant excess risk of headaches (OR:3.86: 95%CI:1.74–8.54) and respiratory problems (OR:2.43; 95%CI:1.02–5.79) among uninformed paid workers. Seamen, the group most exposed to the fuel-oil, were the worst informed and registered the highest frequency of toxicological problems.

Conclusion

Proper health-protection briefing was associated with greater use of protective devices and lower frequency of health problems. Among seamen, however, the results indicate poorer dissemination of information and the need of specific guidelines for removing fuel-oil at sea.
Presumptive identification of Candida species other than C. albicans, C. krusei, and C. tropicalis with the chromogenic medium CHROMagar Candida
Authors: Hospenthal Duane R , Beckius Miriam L , Floyd Karon L , Horvath Lynn L , Murray Clinton K
Published: January 2006

Background

CHROMagar Candida (CaC) is increasingly being reported as a medium used to differentiate Candida albicans from non-albicans Candida (NAC) species. Rapid identification of NAC can assist the clinician in selecting appropriate antifungal therapy. CaC is a differential chromogenic medium designed to identify C. albicans, C. krusei, and C. tropicalis based on colony color and morphology. Some reports have proposed that CaC can also reliably identify C. dubliniensis and C. glabrata.

Methods

We evaluated the usefulness of CaC in the identification of C. dubliniensis, C. famata, C. firmetaria, C. glabrata, C. guilliermondii, C. inconspicua, C. kefyr, C. lipolytica, C. lusitaniae, C. norvegensis, C. parapsilosis, and C. rugosa.

Results

Most NAC produced colonies that were shades of pink, lavender, or ivory. Several isolates of C. firmetaria and all C. inconspicua produced colonies difficult to differentiate from C. krusei. Most C. rugosa isolates produced unique colonies with morphology like C. krusei except in a light blue-green color. C. glabrata isolates produced small dark violet colonies that could be differentiated from the pink and lavender colors produced by other species. All seventeen isolates of C. dubliniensis produced green colonies similar to those produced by C. albicans.

Conclusion

C. glabrata and C. rugosa appear distinguishable from other species using CaC. Some NAC, including C. firmetaria and C. inconspicua, could be confused with C. krusei using this medium.
Common carotid arterial interadventitial distance (diameter) as an indicator of the damaging effects of age and atherosclerosis, a cross-sectional study of the Atherosclerosis Risk in Community Cohort Limited Access Data (ARICLAD), 1987–89
Authors: Eigenbrodt Marsha L , Bursac Zoran , Rose Kathryn M , Couper David J , Tracy Richard E , Evans Gregory W , Brancati Frederick L , Mehta Jawahar L
Published: January 2006

Background

The effect of age on common carotid artery diameter is unclear for varying atherosclerosis risk levels.

Methods

Cross-sectional data from the Atherosclerosis Risk in Communities Limited Access Data set were used to estimate the association of age with B-mode ultrasound common carotid artery diameter for three atherosclerosis risk levels. Based on information from clinical examinations, B-mode ultrasounds, questionnaires, blood and other tests, participants were categorized into three groups: pre-existing disease (prevalent stroke and/or coronary heart disease), high risk group (no pre-existing disease, but prevalent diabetes, hypertension, plaques/shadowing, body mass index >= 30, current smoking, or hyperlipidemia), and a low risk group (no pre-existing disease, no plaques/shadowing, and no major elevated risk factors). Multivariable linear regression analyses modeled the common carotid artery diameter relationship with age.

Results

Age was positively and significantly associated with common carotid artery diameter after risk factor adjustment in the overall sample, but age had a larger effect among persons with evidence of atherosclerosis (interaction p < 0.05). Each year of older age was associated with 0.03 mm larger diameter/year among persons with pre-existing disease, with 0.027 mm larger diameter/year in the high risk group, but only 0.017 mm/year among the low risk group. Results were qualitatively similar using plaques/shadowing status to indicate atherosclerosis severity.

Conclusion

The significant impact of age on common carotid artery diameter among low risk, middle-aged, black and white men and women suggests arterial remodelling may occur in the absence of identified risk factors. The significantly larger impact of age among persons with, compared to persons without identified atherosclerosis or its risk factors, suggests that arterial remodelling may be an indicator of exposure duration.
A Phase I Trial of Pox PSA vaccines (PROSTVAC®-VF) with B7-1, ICAM-1, and LFA-3 co-stimulatory molecules (TRICOM™) in Patients with Prostate Cancer
Authors: DiPaola RS , Plante M , Kaufman H , Petrylak DP , Israeli R , Lattime E , Manson K , Schuetz T
Published: January 2006

Purpose

Based on previous studies that demonstrated the safety profile and preliminary clinical activity of prostate specific antigen (PSA) targeted therapeutic vaccines, as well as recent laboratory data supporting the value of the addition of co-stimulatory molecules B7-1, ICAM-1, and LFA-3 (designated TRICOM™) to these vaccines, we conducted a Phase I study to evaluate the safety and immunogenicity of a novel vaccinia and fowlpox vaccine incorporating the PSA gene sequence and TRICOM.

Methods

In this study, ten patients with androgen independent prostate cancer with or without metastatic disease were enrolled. Patients were treated with 2 × l08pfu of a recombinant vaccinia virus vaccine (PROSTVAC-V) followed by 1 × 109pfu of the booster recombinant fowlpox virus (PROSTVAC-F) both with gene sequences for PSA and TRICOM. The mean age of patients enrolled in the study was 70 (range 63 to 79). The mean PSA at baseline was 434 (range 9 – 1424).

Results

There were no deaths, and no Grade 3 or 4 adverse events. The most commonly reported adverse events, regardless of causality, were injection site reactions and fatigue. One serious adverse event (SAE) occurred that was unrelated to vaccine; this patient developed progressive disease with a new sphenoid metastasis. PSA was measured at week 4 and week 8. Four patients had stable disease (with less than 25% increase in PSA) through the week 8 study period. Anti-PSA antibodies were not induced with therapy: however, anti-vaccinia titers increased in all patients.

Conclusion

This study demonstrated that vaccination with PROSTVAC-V and PROSTVAC-F combined with TRICOM is well-tolerated and generated an immune response to vaccinia. Therefore, PROSTVAC-VF/TRICOM represents a feasible therapeutic approach for further phase II and III study in patients with prostate cancer.
A novel method of modifying immune responses by vaccination with lipiodol-siRNA mixtures
Authors: Ichim Thomas E , Popov Igor A , Riordan Neil H , Izadi Hamid , Zhong Zaohui , Yijian Li , Sher Salman , Oleinik Eugenia K
Published: January 2006

The dendritic cell (DC) possesses the ability to stimulate both T helper 1 (Th1) and Th2 responses depending on activation stimuli. Although it is known that chemically or genetically modified DC can be used therapeutically to steer immune responses towards either Th1 or Th2, cellular therapy with ex vivo manipulated DC is clinically difficult. Here we demonstrate a novel method of switching immune responses from Th1 to Th2 through in vivo immune modulation by administration of siRNA. We demonstrate that siRNA targeting of the IL-12p35 gene leads to a Th2 bias in vitro through an IL-10 dependent mechanism. In vivo administration of siRNA admixed with the oil-based contrast agent lipiodol in the presence of antigen and adjuvant induced a deviation in recall response to reduced production of IFN-γ and augmented IL-4 response using either KLH or ovalbumin. This simple method of in vivo modification of immune response possesses therapeutic potential in Th1-mediated diseases such as multiple sclerosis and autoimmune diabetes.
Web-based data collection: detailed methods of a questionnaire and data gathering tool
Authors: Cooper Charles J , Cooper Sharon P , del Junco Deborah J , Shipp Eva M , Whitworth Ryan , Cooper Sara R
Published: January 2006

There have been dramatic advances in the development of web-based data collection instruments. This paper outlines a systematic web-based approach to facilitate this process through locally developed code and to describe the results of using this process after two years of data collection. We provide a detailed example of a web-based method that we developed for a study in Starr County, Texas, assessing high school students' work and health status. This web-based application includes data instrument design, data entry and management, and data tables needed to store the results that attempt to maximize the advantages of this data collection method. The software also efficiently produces a coding manual, web-based statistical summary and crosstab reports, as well as input templates for use by statistical packages.

Overall, web-based data entry using a dynamic approach proved to be a very efficient and effective data collection system. This data collection method expedited data processing and analysis and eliminated the need for cumbersome and expensive transfer and tracking of forms, data entry, and verification. The code has been made available for non-profit use only to the public health research community as a free download [1].
Degradation of small leucine-rich repeat proteoglycans by matrix metalloprotease-13: identification of a new biglycan cleavage site
Authors: Monfort Jordi , Tardif Ginette , Reboul Pascal , Mineau François , Roughley Peter , Pelletier Jean-Pierre , Martel-Pelletier Johanne
Published: January 2006

A major and early feature of cartilage degeneration is proteoglycan breakdown. Matrix metalloprotease (MMP)-13 plays an important role in cartilage degradation in osteoarthritis (OA). This MMP, in addition to initiating collagen fibre cleavage, acts on several proteoglycans. One of the proteoglycan families, termed small leucine-rich proteoglycans (SLRPs), was found to be involved in collagen fibril formation/interaction, with some members playing a role in the OA process. We investigated the ability of MMP-13 to cleave members of two classes of SLRPs: biglycan and decorin; and fibromodulin and lumican. SLRPs were isolated from human normal and OA cartilage using guanidinium chloride (4 mol/l) extraction. Digestion products were examined using Western blotting. The identities of the MMP-13 degradation products of biglycan and decorin (using specific substrates) were determined following electrophoresis and microsequencing. We found that the SLRPs studied were cleaved to differing extents by human MMP-13. Although only minimal cleavage of decorin and lumican was observed, cleavage of fibromodulin and biglycan was extensive, suggesting that both molecules are preferential substrates. In contrast to biglycan, decorin and lumican, which yielded a degradation pattern similar for both normal and OA cartilage, fibromodulin had a higher level of degradation with increased cartilage damage. Microsequencing revealed a novel major cleavage site (... G177/V178) for biglycan and a potential cleavage site for decorin upon exposure to MMP-13. We showed, for the first time, that MMP-13 can degrade members from two classes of the SLRP family, and identified the site at which biglycan is cleaved by MMP-13. MMP-13 induced SLRP degradation may represent an early critical event, which may in turn affect the collagen network by exposing the MMP-13 cleavage site in this macromolecule. Awareness of SLRP degradation products, especially those of biglycan and fibromodulin, may assist in early detection of OA cartilage degradation.
Therapeutic impact of the ethyl acetate extract of Tripterygium wilfordiiHook F on nephritis in NZB/W F1 mice
Authors: Tao Xuelian , Fan Fred , Hoffmann Victoria , Longo Nancy S , Lipsky Peter E
Published: January 2006

This study was designed to examine the potential use of the ethyl acetate (EA) extract of Tripterygium wilfordii Hook F (TwHF), a Chinese herbal medicine, in the treatment of systemic lupus erythematosus. A total of 48 28-week-old female NZB/W F1 mice were randomly divided into three groups and orally administered vehicle or the EA extract of TwHF at 18.25 mg/kg (EAlow) or 36.5 mg/kg (EAhigh) for 14 weeks. Proteinuria and serum anti-double-stranded (ds)DNA antibody titers were assayed before and after treatment. At the end of treatment, all animals were sacrificed and pathological changes in the kidneys were examined by observers blinded to the treatment regimens. Immunohistological studies were carried out on kidneys and spleens. At 28 weeks of age, proteinuria (>30 mg/dl) and anti-dsDNA antibodies were found in all mice in the three groups. Fourteen, sixteen and fifteen mice in the vehicle, EAlow and EAhigh groups, respectively, completed at least four weeks of treatment. At the end of treatment, the mean proteinuria of the EAlow and EAhigh groups was significantly less than that of the vehicle group and no different from proteinuria at the onset of treatment. Histological evidence of glomerulonephritis, glomerular deposition of IgG and complement 3 and cellular infiltration in the interstitium and perivascular regions were significantly less severe in the EA extract treated mice than in vehicle treated mice. Treatment with the EA extract significantly inhibited the progression of kidney disease in NZB/W F1 mice, though had no significant effect on the levels of anti-dsDNA antibody.
Psychological approaches to somatisation in developing countries
Authors: Patel Vikram , Sumathipala Athula
Published: January 2006

Medically unexplained somatic complaints are among the most common clinical presentations in primary care in developing countries and they are a considerable burden for patients and the healthcare system. They are assumed to be the result of psychosocial factors, and the process by which symptoms are experienced is termed somatisation. Common mental disorders, somatoform disorders and socio-economic adversities are the major risk factors for these complaints. There is evidence suggesting that cognitive–behavioural therapy, which has proven efficacy for somatoform disorders in the developed world, can be used in developing countries with some adaptations (e.g. by simplifying the content so that it can be applied in primary care by non-specialist health practitioners; using culturally appropriate analogies; and delivering the intervention over fewer and shorter sessions). The main components of such an intervention are presented in this article.
Fear of speaking: chronic anxiety and stammering
Authors: Craig Ashley , Tran Yvonne
Published: January 2006

Stammering results in involuntary disruption of a person's capacity to speak. It begins at an early age and can persist for life for at least 20% of those stammering at 2 years old. Although the aetiological role of anxiety in stammering has not been determined, evidence is emerging that suggests people who stammer are more chronically and socially anxious than those who do not. This is not surprising, given that the symptoms of stammering can be socially embarrassing and personally frustrating, and have the potential to impede vocational and social growth. Implications for DSM–IV diagnostic criteria for stammering and current treatments of stammering are discussed. We hope that this article will encourage a better understanding of the consequences of living with a speech or fluency disorder as well as motivate the development of treatment protocols that directly target the social fears associated with stammering.
A balancing act: developing curricula for balanced care within community psychiatry†
Authors: Valsraj Koravangattu Menon , Lygo-Baker Simon
Published: January 2006

Mental health services are moving towards a balanced-care model. The shift recommended by the World Health Organization is currently being reflected only in service delivery, and has not been clearly reflected in the training curriculum. This change in service delivery has implications for teaching and learning. This article looks at how best the curriculum can incorporate aspects of community psychiatry and hospital work for medical students and junior doctors in training. This move towards balanced care also requires teaching staff to consider how to make use of collaborative working and to develop effective working relationships.
What needs balancing?
Authors: Bhugra Dinesh
Published: January 2006

Curriculum is not the same as syllabus. The latter is a statement of topics to be studied in a specific course. The former ranges from a statement of purpose, aims and contents (the paper curriculum) to how these are applied in practice, what learners do and the behaviours, knowledge and performances that they see as important. The Postgraduate Medical Education and Training Board (PMETB) defines curriculum as:
Combining Functional and Diffusion Tensor MRI
Authors: KIM DAE‐SHIK , KIM MINA
Published: January 2006

Functional magnetic resonance imaging (fMRI) of the perceptual, motor, and cognitive capacities in humans is of increasing importance for basic and clinical neurosciences. The explanatory power of current fMRI techniques could be greatly expanded, however, if the pattern of the neuronal connections between the active cortical areas could likewise be visualized. In this study, we acquired blood‐oxygenation level dependent (BOLD) fMRI signals during the stimulation of subjects with a set of localizer stimuli for cortical visual areas. Subsequently, diffusion tensor imaging (DTI) data from the same subjects were obtained, and the activation areas identified through fMRI were utilized as seeding points for 3D DTI fiber reconstruction algorithms. The methods developed in this study have the potential to lay a foundation forin vivoneuroanatomy and the ability for noninvasive longitudinal studies of brain development.
Investigating the Functional Role of Callosal Connections with Dynamic Causal Models
Authors: STEPHAN KLAAS E. , PENNY WILL D. , MARSHALL JOHN C. , FINK GEREON R. , FRISTON KARL J.
Published: January 2006

The anatomy of the corpus callosum has been described in considerable detail. Tracing studies in animals and human postmortem experiments are currently complemented by diffusion‐weighted imaging, which enables noninvasive investigations of callosal connectivity to be conducted. In contrast to the wealth of anatomical data, little is known about the principles by which interhemispheric integration is mediated by callosal connections. Most importantly, we lack insights into the mechanisms that determine the functional role of callosal connections in a context‐dependent fashion. These mechanisms can now be disclosed by models of effective connectivity that explain neuroimaging data from paradigms that manipulate interhemispheric interactions. In this article, we demonstrate that dynamic causal modeling (DCM), in conjunction with Bayesian model selection (BMS), is a powerful approach to disentangling the various factors that determine the functional role of callosal connections. We first review the theoretical foundations of DCM and BMS before demonstrating the application of these techniques to empirical data from a single subject.
Diffusion Tensor Imaging of the Spinal Cord
Authors: MAIER STEPHAN E. , MAMATA HATSUHO
Published: January 2006

The spinal cord is an important part of the nervous system and provides the connection of the brain with the periphery. It consists not only of a large number of longitudinal fibers, but also contains collateral fibers and a central gray matter structure, which are part of autonomous circuits. Magnetic resonance diffusion tensor imaging can reveal this complex fiber architecture in great detail. This report summarizes the normal findings for ADC, diffusion anisotropy, and diffusion eigenvector directions in the spinal cord. Sagittal and axial diffusion‐weighted images of the spinal cord were obtained with line scan diffusion imaging (LSDI) in adults, children, infants, and a spinal cord specimen.
White Matter Tractography by Means of Turboprop Diffusion Tensor Imaging
Authors: ARFANAKIS KONSTANTINOS , GUI MINZHI , LAZAR MARIANA
Published: January 2006

White matter fiber‐tractography by means of diffusion tensor imaging (DTI) is a noninvasive technique that provides estimates of the structural connectivity of the brain. However, conventional fiber‐tracking methods using DTI are based on echo‐planar image acquisitions (EPI), which suffer from image distortions and artifacts due to magnetic susceptibility variations and eddy currents. Thus, a large percentage of white matter fiber bundles that are mapped using EPI‐based DTI data are distorted, and/or terminated early, while others are completely undetected. This severely limits the potential of fiber‐tracking techniques. In contrast, Turboprop imaging is a multiple‐shot gradient and spin‐echo (GRASE) technique that provides images with significantly fewer susceptibility and eddy current‐related artifacts than EPI. The purpose of this work was to evaluate the performance of fiber‐tractography techniques when using data obtained with Turboprop‐DTI. All fiber pathways that were mapped were found to be in agreement with the anatomy. There were no visible distortions in any of the traced fiber bundles, even when these were located in the vicinity of significant magnetic field inhomogeneities. Additionally, the Turboprop‐DTI data used in this research were acquired in less than 19 min of scan time. Thus, Turboprop appears to be a promising DTI data acquisition technique for tracing white matter fibers.
White Matter and Behavioral Neurology
Authors: FILLEY CHRISTOPHER M.
Published: January 2006

Although the study of higher brain function has traditionally focused on the cortical gray matter, recent years have witnessed the recognition that white matter also makes an important contribution to cognition and emotion. White matter comprises nearly half the brain volume and plays a key role in development, aging, and many neurologic and psychiatric disorders across the life span. More than 100 disorders exist in which white matter neuropathology is the primary or a prominent feature. A variety of neurobehavioral syndromes may result from these disorders; the concept of white matter dementia has been introduced as characteristic of many patients with white matter involvement, and a wide range of focal neurobehavioral syndromes and psychiatric disorders can also be related to dysfunction of myelinated tracts. Understanding the neurobehavioral aspects of white matter disorders is important for clinical diagnosis, treatment, prognosis, and research on brain‐behavior relationships. Central to these investigations is the use of modern neuroimaging techniques, which have already provided substantial information on the characterization of white matter and its disorders, and which promise to advance our knowledge further with continued innovation. Diffusion tensor imaging is an exciting method that will assist with the identification of critical white matter tracts in the brain, and the localization of specific lesions that can be correlated with neurobehavioral syndromes. A behavioral neurology of white matter is thus emerging in which clinical observation combined with sophisticated neuroimaging will enable elucidation of the role of white matter connectivity in the distributed neural networks subserving higher brain function.
Adolescents with Disruptive Behavior Disorder Investigated Using an Optimized MR Diffusion Tensor Imaging Protocol
Authors: LI TIE‐QIANG , MATHEWS VINCENT P. , WANG YANG , DUNN DAVID , KRONENBERGER WILLIAM
Published: January 2006

Adolescents with disruptive behavior disorder (DBD) and controls were investigated using an optimized MR diffusion tensor imaging (DTI) protocol in order to assess any possible structural abnormalities associated with DBD. Thirty‐six patients and 40 normal subjects were examined. The extracted diffusion fractional anisotropy (FA) results demonstrate that for the DBD patients there is significantly reduced FA in both the frontal and left temporal regions. The largest brain area with significantly reduced FA is located within the arcuate fasciculus, which has projections extending from the temporal lobe to the frontal lobe along the lateral ventricle, lateral to the tapetum. The reduced FA reflects directly a lower extent of myelination and less coherent fiber track structures in the fasciculus, which in turn may indicate communication weakness among the associated cortical areas. The detected white matter microstructural abnormality, therefore, may be related to the developmental deficits observed in the patient group.
Principal Diffusion Direction in Peritumoral Fiber Tracts: Color Map Patterns and Directional Statistics
Authors: FIELD AARON S. , WU YU‐CHIEN , ALEXANDER ANDREW L.
Published: January 2006

The ability of diffusion tensor imaging (DTI) to probe the ultrastructural properties of biological tissues presents new possibilities for DTI‐based tissue characterization, with the potential for greater pathologic specificity than conventional imaging methods. This is urgently needed in the diagnosis and treatment of cerebral neoplasms, where clinical decisions depend on the ability to discriminate tumor‐involved from uninvolved tissue, a major shortcoming of conventional imaging. Several investigators have attempted to make this determination on the basis of the apparent diffusion coefficient (ADC) or the fractional anisotropy (FA), with mixed results. The directionally encoded color map, with hues reflecting tensor orientation and intensity weighted by FA, provides an aesthetic and informative summary of DTI features throughout the brain in an easily interpreted format. The use of these maps is becoming increasingly common in both basic and clinical research, as well as in purely clinical settings. These examples serve to demonstrate our approach to the quantitation of regional diffusion tensor distributions using directional statistical methods.
Transcription Factor Decoys: A New Model for Disease Intervention
Authors: MANN MICHAEL J.
Published: January 2006

Transcription factor proteins regulate gene expression via binding to specific DNA sequences found in the promoter/enhancer regions of the genes they control. Although most transcription factor binding has been associated with an increase in gene expression, gene suppression has also been described. Transcription factor decoys are molecules that mimic the binding sites for transcription factor proteins, and compete with promoter regions to absorb this binding activity in the cell nucleus. By blocking transcription factor‐chromosomal DNA interaction, these molecules provide a powerful means to manipulate the regulation of gene expression, particularly as transcription factors are increasingly understood to alter gene activation during the course of normal and pathologic processes in cell biology. As methods for cellular and nuclear delivery of these agents improve, the increasing use of transcription factor decoys, both as investigative and therapeutic tools, promises to have a significant impact on our understanding of and ability to treat human disease.
DNA Damage Produced by 125I‐Triplex‐Forming Oligonucleotides as a Measure of Their Succesful Delivery into Cell Nuclei
Authors: PANYUTIN IRINA V. , SEDELNIKOVA OLGA A. , BONNER WILLIAM M. , PANYUTIN IGOR G. , NEUMANN RONALD D.
Published: January 2006

Decay of an Auger‐electron‐emitting radioisotope can knock out a targeted gene by producing DNA strand breaks within its sequence. For delivery of Auger emitters to genomic targets we used triplex‐forming oligonucleotides (TFOs) that bind specifically to their target sequences by forming hydrogen bonds within the major groove of the target duplex. We named this approach antigene radiotherapy. In our previous studies, we demonstrated that 125I‐labeled TFOs targeted against the human MDR1 gene produced sequence‐specific double strand breaks (DSBs) within this gene in live cultured cells. We also found that conjugation of TFO with nuclear localization signal peptide significantly increased the efficiency of targeting. To screen the wide variety of possible TFO modifications a sensitive and robust assay of DNA damage produced by such 125I‐TFOs would be highly desirable. Recently we showed a direct correspondence between the number of decays of 125I incorporated into DNA as 125I‐UdR and the number of histone γ‐H2AX foci per cell revealed by staining with γ‐H2AX antibodies. The technique is 100‐fold more sensitive than other DSB‐detection methods, thus it is possible to detect as few as an average of 0.5 DSBs per cell in a population of cultured cells. Here we applied this method to evaluate the intracellular DNA damage produced by two 125I‐TFOs, the first targeted to the single‐copy HPRT gene (125I‐TFO‐HPRT) and second to a multicopy repeated sequence (GA)n that occurs almost 7000 times in the human genome (125I‐TFO‐GA). DNA damage produced by 125I‐TFO was assessed by staining the cells with γ‐H2AX antibody followed by either direct counting γ‐H2AX foci or by measuring the γ‐H2AX signal using flow cytometry. Both methods produced quantitatively close results; 125I‐TFO‐GA with multiple nuclear targets produced on average 1.93 times more γ‐H2AX foci per cell and generated 1.96 times increase in γ‐H2AX antibody staining signal than 125I‐TFO‐HPRT with a single target. The γ‐H2AX‐based assay requires considerably less time and effort than the direct measurement of DSB by Southern hybridization applied previously. Therefore, we believe that γ‐H2AX‐based measurement of DNA damage could be useful for evaluation and cellular DNA accessibility by 125I‐labeled DNA targeting agents.
Novel MDM2 p53‐Independent Functions Identified through RNA Silencing Technologies
Authors: ZHANG ZHUO , WANG HUI , LI MAO , RAYBURN ELIZABETH , AGRAWAL SUDHIR , ZHANG RUIWEN
Published: January 2006

The MDM2 oncogene has an important role in human carcinogenesis and has been suggested as a novel target for cancer therapy. Many published in vitro and in vivo investigations have demonstrated that various MDM2 inhibitors including antisense oligonucleotides, siRNA, and small molecule MDM2 inhibitors have antitumor activity in in vitro and in vivo human cancer models, used alone or in combination with cancer chemotherapeutics and radiation therapy. For example, the mixed backbone antisense oligonucleotide developed in our laboratory specifically inhibited MDM2 expression in a dose‐ and time‐dependent manner, resulting in significant antitumor activity in vitro and in vivo. Interestingly, the antisense MDM2 inhibitors have a broad spectrum of antitumor activities in human cancers, regardless of p53 status. These results prompted new investigations into the p53‐independent functions of MDM2. This article summarizes the biochemical and molecular studies of the role of MDM2 in the regulation of p21 and E2F1 expression, stability and function, providing evidence for the utility of RNA‐silencing technologies, including antisense oligonucleotides and siRNAs.