bluuebunny/crossref_metadata_2025 huggingface dataset:
Treadmill Exercise Rehabilitation Improves Ambulatory Function and Cardiovascular Fitness in Patients With Chronic Stroke
Authors: Macko Richard F. , Ivey Frederick M. , Forrester Larry W. , Hanley Daniel , Sorkin John D. , Katzel Leslie I. , Silver Kenneth H. , Goldberg Andrew P.
Published: September 2005

Background and Purpose—

Physical inactivity propagates disability after stroke through physical deconditioning and learned nonuse. We investigated whether treadmill aerobic training (T-AEX) is more effective than conventional rehabilitation to improve ambulatory function and cardiovascular fitness in patients with chronic stroke.

Methods—

Sixty-one adults with chronic hemiparetic gait after ischemic stroke (>6 months) were randomized to 6 months (3×/week) progressive T-AEX or a reference rehabilitation program of stretching plus low-intensity walking (R-CONTROL). Peak exercise capacity (V
o
2
peak),
o
2
consumption during submaximal effort walking (economy of gait), timed walks, Walking Impairment Questionnaire (WIQ), and Rivermead Mobility Index (RMI) were measured before and after 3 and 6 months of training.

Results—

Twenty-five patients completed T-AEX and 20 completed R-CONTROL. Only T-AEX increased cardiovascular fitness (17% versus 3%, δ% T-AEX versus R-CONTROL,
P
<0.005). Group-by-time analyses revealed T-AEX improved ambulatory performance on 6-minute walks (30% versus 11%,
P
<0.02) and mobility function indexed by WIQ distance scores (56% versus 12%,
P
<0.05). In the T-AEX group, increasing training velocity predicted improved V
o
2
peak (
r
=0.43,
P
<0.05), but not walking function. In contrast, increasing training session duration predicted improved 6-minute walk (
r
=0.41,
P
<0.05), but not fitness gains.

Conclusions—

T-AEX improves both functional mobility and cardiovascular fitness in patients with chronic stroke and is more effective than reference rehabilitation common to conventional care. Specific characteristics of training may determine the nature of exercise-mediated adaptations.
Diagnostic Performance of Duplex Ultrasound in Patients Suspected of Carotid Artery Disease
Authors: Heijenbrok-Kal Majanka H. , Nederkoorn Paul J. , Buskens Erik , van der Graaf Yolanda , Myriam Hunink M.G.
Published: September 2005

Background and Purpose—

To evaluate duplex ultrasonographic thresholds for the determination of 70% to 99% stenosis of the ipsilateral and contralateral internal carotid artery in patients with symptoms of amaurosis fugax, transient ischemic attack (TIA), or minor stroke based on 2 criteria: maximizing accuracy and optimizing cost-effectiveness and to compare these with current recommendations.

Methods—

From January 1997 to January 2000, a prospective multicenter study was conducted including 350 consecutive patients with symptoms of amaurosis fugax, TIA, or minor stroke who underwent bilateral duplex ultrasonography and digital subtraction angiography. A linear regression analysis was performed to estimate the degree of angiographic stenosis as a function of the peak systolic velocity (PSV). PSV thresholds were calculated for the ipsilateral and contralateral carotid arteries based on maximizing accuracy and optimizing cost-effectiveness.

Results—

The PSV measurements significantly overestimated the angiographic stenosis in the contralateral artery (9.5%; 95% CI, 6.3% to 12.7%) compared with the ipsilateral carotid artery. The recommended PSV threshold for the diagnosis of 70% to 99% stenosis is 230 cm/s. Maximizing accuracy, the optimal PSV threshold for the ipsilateral artery was 280 cm/s, and for the contralateral artery, 370 cm/s for diagnosing a 70% to 99% stenosis. Optimizing cost-effectiveness, the optimal PSV threshold was 220 cm/s for ipsilateral and 290 cm/s for contralateral carotid arteries.

Conclusions—

PSV measurements overestimate the degree of angiographic stenosis in the contralateral carotid artery in patients with symptoms of amaurosis fugax, TIA, or minor stroke. Separate PSV thresholds should be used for the ipsilateral and contralateral carotid artery. PSV thresholds that optimize cost-effectiveness differ from the recommended thresholds and from thresholds that maximize accuracy.
Associations of Inflammatory and Hemostatic Variables With the Risk of Recurrent Stroke
Authors: Woodward Mark , Lowe Gordon D.O. , Campbell Duncan J. , Colman Sam , Rumley Ann , Chalmers John , Neal Bruce C. , Patel Anushka , Jenkins Alicia J. , Kemp Bruce E. , MacMahon Stephen W.
Published: September 2005

Background and Purpose—

Several prospective studies have shown significant associations between plasma fibrinogen, viscosity, C-reactive protein (CRP), fibrin
d
-dimer, or tissue plasminogen activator (tPA) antigen and the risk of primary cardiovascular events. Little has been published on the associations of these variables with recurrent stroke. We studied such associations in a nested case-control study derived from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS).

Methods—

Nested case-control study of ischemic (n=472) and hemorrhagic (n=83) strokes occurring during a randomized, placebo-controlled multicenter trial of perindopril-based therapy in 6105 patients with a history of stroke or transient ischemic attack. Controls were matched for age, treatment group, sex, region, and most recent qualifying event at entry to the parent trial.

Results—

Fibrinogen and CRP were associated with an increased risk of recurrent ischemic stroke after accounting for the matching variables and adjusting for systolic blood pressure, smoking, peripheral vascular disease, and statin and antiplatelet therapy. The odds ratio for the last compared with the first third of fibrinogen was 1.34 (95% CI, 1.01 to 1.78) and for CRP was 1.39 (95% CI, 1.05 to 1.85). After additional adjustment for each other, these 2 odds ratios stayed virtually unchanged. Plasma viscosity, tPA, and
d
-dimer showed no relationship with recurrent ischemic stroke, although tPA was significant for lacunar and large artery subtypes. Although each of these variables showed a negative relationship with recurrent hemorrhagic stroke, none of these relationships achieved statistical significance.

Conclusions—

Fibrinogen and CRP are risk predictors for ischemic but not hemorrhagic stroke, independent of potential confounders.
Determinants of Caregiving Burden and Quality of Life in Caregivers of Stroke Patients
Authors: McCullagh Emily , Brigstocke Gavin , Donaldson Nora , Kalra Lalit
Published: September 2005

Background and Purpose—

A large proportion of disabled stroke survivors live at home and are supported by informal caregivers. Identification of determinants of caregiver burden will help to target caregiver interventions.

Methods—

Data on patient, caregiver, and health and social support characteristics were collected prospectively over 1 year in 232 stroke survivors in a randomized trial of caregiver training. The contribution of these variables to caregiver burden score (CBS) and quality of life (QOL) measures at 3 months and 1 year was analyzed using regression models.

Results—

Stroke patients had a mean age of 74±11 years, and 120 (52%) were men. The mean age of caregivers was 65.7±12.5 years, 149 (64%) were females, and 116 (50%) had received caregiver training. The mean CBS was 48±13 and 38±11 (score range of bad to good 88 to 22) and QOL score was 75±16 and 75±15 (score range of bad to good 0 to 100) at 3 months and 1 year, respectively. CBS and QOL correlated with each other and with patient (age, dependency, and mood), caregiver (age, gender, mood, and training), and support (social services and family networks) variables. Of these, only patient and caregiver emotional status, caregiver age and gender, and participation in caregiver training were independent predictors of either outcome at 3 months. Patient dependency and family support were additional independent predictors at 1 year. Social services support predicted institutionalization but not caregiver outcomes.

Conclusion—

Advancing age and anxiety in patients and caregivers, high dependency, and poor family support identify caregivers at risk of adverse outcomes, which may be reduced by caregiver training.
Interannual Variability of Patterns of Atmospheric Mass Distribution
Authors: Trenberth Kevin E. , Stepaniak David P. , Smith Lesley
Published: September 2005

Using the 40-yr European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis (ERA-40) for 1958 to 2001, adjusted for bias over the southern oceans prior to 1979, an analysis is made of global patterns of monthly mean anomalies of atmospheric mass, which is approximately conserved globally. It differs from previous analyses of atmospheric circulation by effectively area weighting surface or sea level pressure that diminishes the role of high latitudes. To examine whether global patterns of behavior exist requires analysis of all seasons together (as opposite seasons occur in each hemisphere). Empirical orthogonal function (EOF) analysis, R-mode varimax-rotated EOF analysis, and cyclostationary EOF (CSEOF) analysis tools are used to explore patterns and variability on interannual and longer time scales. Clarification is given of varimax terminology and procedures that have been previously misinterpreted. The dominant global monthly variability overall is associated with the Southern Hemisphere annular mode (SAM), which is active in all months of the year. However, it is not very coherent from month to month and exhibits a great deal of natural unforced variability. The third most important pattern is the Northern Hemisphere annular mode (NAM) and associated North Atlantic Oscillation (NAO), which is the equivalent Northern Hemisphere expression. Neither of these is really a global mode, although they covary on long time scales in association with tropical or external forcing. For monthly data, the second mode is coherent with Niño-3.4 sea surface temperatures and thus corresponds to El Niño–Southern Oscillation (ENSO), which is truly global in extent. It exhibits more coherent evolution with time and projects strongest onto the interannual variability, where it stands out by far as the dominant mode in the CSEOF analysis. The CSEOF analysis extracts the patterns phase locked with annual cycle and reveals their evolution throughout the year. Standard EOF and varimax analyses are not able to evolve with time of year unless the analysis is stratified by season. Varimax analysis is able to extract the SAM, NAM, and ENSO modes very well, however.
Spatial Patterns of Preinstrumental Moisture Variability in the Southern Canadian Cordillera
Authors: Watson Emma , Luckman Brian H.
Published: September 2005

Extreme wet and dry intervals of the last 350 yr in the Canadian Cordillera and adjacent United States are examined using a network of 25 tree-ring-based precipitation and Palmer Drought Severity Index (PDSI) reconstructions. Reconstructed twentieth-century-mapped patterns compare well with patterns based on the instrumental records at both annual and decadal scales. During the most extreme events, dry conditions occurred over the entire area. The longest widespread drought in the last 350 yr occurred from 1917 to 1941. Shorter intervals of more severely dry conditions occurred in the early 1720s, 1750s, 1790s, 1860s–70s, and the 1890s. Many of the driest individual years and most extreme dry periods of <7 yr are reconstructed for the eighteenth century. The longest, wettest periods identified by these reconstructions occurred in the early twentieth century. In agreement with published studies that explore links between instrumental precipitation records from the region and conditions in the Pacific Ocean, the reconstructed records show that drier (wetter)-than-normal conditions are associated with El Niño (La Niña) events and the positive (negative) phase of the Pacific decadal oscillation (PDO).
Maintenance of the Sea-Ice Edge
Authors: Bitz C. M. , Holland M. M. , Hunke E. C. , Moritz R. E.
Published: September 2005

A coupled global climate model is used to evaluate processes that determine the equilibrium location of the sea-ice edge and its climatological annual cycle. The extent to which the wintertime ice edge departs from a symmetric ring around either pole depends primarily on coastlines, ice motion, and the melt rate at the ice–ocean interface. At any location the principal drivers of the oceanic heat flux that melts sea ice are absorbed solar radiation and the convergence of heat transported by ocean currents. The distance between the ice edge and the pole and the magnitude of the ocean heat flux convergence at the ice edge are inversely related. The chief exception to this rule is in the East Greenland Current, where the ocean heat flux convergence just east of the ice edge is relatively high but ice survives due to its swift southward motion and the protection of the cold southward-flowing surface water. In regions where the ice edge extends relatively far equatorward, absorbed solar radiation is the largest component of the ocean energy budget, and the large seasonal range of insolation causes the ice edge to traverse a large distance. In contrast, at relatively high latitudes, the ocean heat flux convergence is the largest component and it has a relatively small annual range, so the ice edge traverses a much smaller distance there. When the model is subject to increased CO2 forcing up to twice preindustrial levels, the ocean heat flux convergence weakens near the ice edge in most places. This weakening reduces the heat flux from the ocean to the base of the ice and tends to offset the effects of increased radiative forcing at the ice surface, so the ice edge retreats less than it would otherwise.
Maintenance of the Midtropospheric North African Summer Circulation: Saharan High and African Easterly Jet
Authors: Chen Tsing-Chang
Published: September 2005

The conspicuous feature of the midtropospheric North African summer circulation is the Saharan high surrounded on its southern rim by the African easterly jet (AEJ). Like a major monsoon circulation, the Saharan high is juxtaposed with the North African divergent center to the east and the eastern Atlantic convergent center to the west. Different from a major monsoon circulation, these pronounced midtropospheric circulation components are overlaid by the western part of the Tibetan high. Because of the unique roles played by the Saharan high and the African easterly jet in the North African summer circulation, an effort is made to explore maintenance mechanisms of these two midtropospheric circulation elements. Major findings of this effort are summarized as follows:In terms of the velocity potential maintenance equation, it is shown that the North African divergent center over the Chad–Sudan region is maintained by the vertical differential heating established by the Saharan thermal-low heating in the lower troposphere and the Saharan radiative cooling in the upper troposphere.The Saharan high is spatially in quadrature with the North African divergent center. It is inferred from the streamfunction budget analysis that the Saharan high is maintained by the east–west circulation, which is formed by the east–west differential heating between the Saharan thermal-low heating and the eastern North Atlantic cooling. This inference is further substantiated by forced barotropic model simulations.The AEJ around the tropical periphery of the Saharan high is almost perpendicular to the equatorward divergent northerlies spilling out of the North African divergent center. The energetic interaction between divergent and rotational flows reveals that this jet is maintained by the Coriolis acceleration associated with these divergent winds.

These findings not only reveal the maintenance mechanism of the Saharan high and the associated AEJ, but also facilitate the search for answers to some problems of the North African summer weather/climate system.
Human-Induced Change in the Antarctic Circumpolar Current
Authors: Fyfe John C. , Saenko Oleg A.
Published: September 2005

Global climate models indicate that the poleward shift of the Antarctic Circumpolar Current observed over recent decades may have been significantly human induced. The poleward shift, along with a significant increase in the transport of water around Antarctica, is predicted to continue into the future. To appreciate the magnitude of the poleward shift it is noted that by century’s end the concomitant shrinking of the Southern Ocean is predicted to displace a volume of water close to that in the entire Arctic Ocean. A simple theory, balancing surface Ekman drift and ocean eddy mixing, explains these changes as the oceanic response to changing wind stress.
Multiconvective Parameterizations as a Multimodel Proxy for Seasonal Climate Studies
Authors: LaRow T. E. , Cocke S. D. , Shin D. W.
Published: September 2005

A six-member multicoupled model ensemble is created by using six state-of-the-art deep atmospheric convective schemes. The six convective schemes are used inside a single model and make up the ensemble. This six-member ensemble is compared against a multianalysis ensemble, which is created by varying the initial start dates of the atmospheric component of the coupled model. Both ensembles were integrated for seven months (November–May) over a 12-yr period from 1987 to 1998. Examination of the sea surface temperature and precipitation show that while deterministic skill scores are slightly better for the multicoupled model ensemble the probabilistic skill scores favor the multimodel approach. Combining the two ensembles to create a larger ensemble size increases the probabilistic skill score compared to the multimodel. This altering physics approach to create a multimodel ensemble is seen as an easy way for small modeling centers to generate ensembles with better reliability than by only varying the initial conditions.
The Anti-Gentilians during the Fascist Regime
Authors: Tarquini Alessandra
Published: September 2005

This article reconstructs an important aspect of fascist ideology: the critiques directed by the main political and cultural groupings among Italian fascists against Giovanni Gentile, from 1922 until his death in 1944. This article seeks to make a significant contribution to the debate on the part played by Gentile during the fascist regime, demonstrating the way in which, and the extent to which, fascism, as realized, represented a form of totalitarianism quite different from the one he had conceived in his theory.
Perceptions of social challenges of adults with autism spectrum disorder
Authors: Sperry Laurie A. , Mesibov Gary B.
Published: September 2005

This study examines perceptions of social challenges by adults with autism spectrum disorder (ASD). The investigators analyzed three separate, regularly scheduled social group meetings attended by a total of 18 adults with ASD where the activity was a discussion of social issues. Participants generated social questions and challenges they had encountered as a result of having autism. The questions were presented to the group for a discussion of potential solutions. Written and audio data were collected and a member check was completed. The data were plumbed for key words and emergent themes to identify major social challenges as viewed by adults with ASD. The emergent themes included relationships at work, developing and maintaining personal relationships, appropriate behaviors around members of the opposite sex, and personal perspectives on having ASD.
Comparison of DSM-IV symptoms in elementary school-age children with PDD versus clinic and community samples
Authors: Gadow Kenneth D. , Devincent Carla J. , Pomeroy John , Azizian Allen
Published: September 2005

This study compares DSM-IV symptoms in children (ages 6 to 12 years) with pervasive developmental disorder (PDD), clinic controls, and community-based samples. Parents/teachers completed the Child Symptom Inventory–4 for four samples: PDD ( N= 284/284) and non-PDD psychiatric clinic referrals ( N= 189/181) and pupils in regular ( N= 385/404) and special ( N= 61/60) education classes. The PDD group received higher symptom severity ratings than the regular education group, but was similar to the non-PDD clinic sample. Screening prevalence rates were highest for ADHD, ODD, and generalized anxiety disorder. PDD subtypes exhibited differentially higher rates of psychiatric symptoms. The magnitude of rater and gender differences in symptom severity ratings was modest. Clinic-referred children with PDD exhibit a pattern of psychiatric symptoms highly similar to nonPDD clinic referrals. Although much additional research is needed on comorbidity, these symptoms have important treatment implications.
Factors associated with stress in mothers of children with autism
Authors: Duarte Cristiane S. , Bordin Isabel A. , Yazigi Latife , Mooney Julia
Published: September 2005

The objective of this case-control study was to investigate the determinants of maternal stress in mothers of children with autism. Mothers of 31 children with autism from mental health clinics were matched by child age/gender and mother age to 31 mothers of children without mental health problems, drawn from public schools and a primary care unit. Logistic regression models showed that the presence of stress in mothers was primarily associated with having a child with autism. However, poor expression of affect, little interest in people, being an older mother, and having a younger child also contributed to increased stress levels. Although having a child with autism was the main factor responsible for stress, the presence of the other factors further increased maternal stress. The implication is that a subgroup of mothers of children with autism is more prone to experience stress, thus requiring special attention from mental health professionals.
Understanding emotions from standardized facial expressions in autism and normal development
Authors: Castelli Fulvia
Published: September 2005

The study investigated the recognition of standardized facial expressions of emotion (anger, fear, disgust, happiness, sadness, surprise) at a perceptual level (experiment 1) and at a semantic level (experiments 2 and 3) in children with autism ( N= 20) and normally developing children ( N= 20). Results revealed that children with autism were as able as controls to recognize all six emotions with different intensity levels, and that they made the same type of errors. These negative findings are discussed in relation to (1) previous data showing specific impairment in autism in recognizing the belief-based expression of surprise, (2) previous data showing specific impairment in autism in recognizing fear, and (3) the convergence of findings that individuals with autism, like patients with amygdala damage, pass a basic emotions recognition test but fail to recognize more complex stimuli involving the perception of faces or part of faces.
A novel splicing mutation of the α-spectrin gene in the original hereditary pyropoikilocytosis kindred
Authors: Costa Daniel B. , Lozovatsky Larisa , Gallagher Patrick G. , Forget Bernard G.
Published: September 2005

Hereditary pyropoikilocytosis (HPP) is a severe hemolytic anemia due to abnormalities of the red blood cell (RBC) membrane skeleton. In the original HPP kindred, there is compound heterozygosity for an allele encoding a structural variant of α-spectrin (L207P) and an α-spectrin allele associated with a defect in α-spectrin production. To identify the molecular defect in the production-defective allele, reticulocyte α-spectrin cDNA from one of the original HPP patients was analyzed. Transcripts from the production-defective, non-L207P allele demonstrated a pattern of abnormal splicing between exons 22 and 23, resulting in insertion of intronic fragments with an in-frame premature termination codon. A G to A substitution at position +5 of the donor consensus splice site of IVS 22 was identified in the inserts. Following gene transfer into tissue culture cells, there was complete absence of normally spliced α-spectrin gene transcripts derived from a minigene containing the IVS 22 +5 mutation.
Skewed T-cell differentiation in patients with indolent non-Hodgkin lymphoma reversed by ex vivo T-cell culture with γc cytokines
Authors: Anichini Andrea , Mortarini Roberta , Romagnoli Luca , Baldassari Paola , Cabras Antonello , Carlo-Stella Carmelo , Gianni Alessandro M. , Di Nicola Massimo
Published: September 2005

The unfavorable clinical evolution in indolent non-Hodgkin lymphomas suggests defective control of neoplastic growth by the immune system. To address this issue, we evaluated phenotype, function, and maturation profile of CD4+ and CD8+ T cells from peripheral-blood, lymph nodes, or bone marrow of patients with B-cell non-Hodgkin lymphoma (NHL) at diagnosis. T cells from these patients frequently showed an activated but apoptosis-prone phenotype with low frequency of tumor-reactive T cells showing a TH2/Tc2 functional profile in the response to autologous tumor. In peripheral blood or in lymph nodes and bone marrow, and, in comparison to healthy donors, patients' T cells showed a skewed differentiation toward Tnaive and Tcentral memory stages, with low expression of granzyme B and perforin. T-cell culture with autologous tumor in the presence of IL-2, IL-15, and autologous bone marrow–derived cells led to massive T-cell expansion and to differentiation of cytotoxic factor+ CD8+ T cells releasing IFN-γ and killing autologous B-cell tumor in an HLA-class I–restricted fashion. These results suggest impaired T-cell differentiation to effector stage in patients with B-cell NHL, but indicate that T-cell responsiveness to γc cytokines is retained, thus allowing to promote generation of antitumor T cells for immune intervention.
Lymphoma incidence patterns by WHO subtype in the United States, 1992-2001
Authors: Morton Lindsay M. , Wang Sophia S. , Devesa Susan S. , Hartge Patricia , Weisenburger Dennis D. , Linet Martha S.
Published: September 2005

Because the causes of most lymphoid neoplasms remain unknown, comparison of incidence patterns by disease subtype may provide critical clues for future etiologic investigations. We therefore conducted a comprehensive assessment of 114 548 lymphoid neoplasms diagnosed during 1992-2001 in 12 Surveillance, Epidemiology, and End Results (SEER) registries according to the internationally recognized World Health Organization (WHO) lymphoma classification introduced in 2001. Cases coded in International Classification of Diseases for Oncology, Second Edition (ICD-O-2), were converted to ICD-O-3 for WHO subtype assignment. Age-specific and age-adjusted rates were compared by sex and race (white, black, Asian). Age-adjusted trends in incidence were estimated by sex and race using weighted least squares log-linear regression. Diverse incidence patterns and trends were observed by lymphoid neoplasm subtype and population. In the elderly (75 years or older), rates of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma increased 1.4% and 1.8% per year, respectively, whereas rates of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) declined 2.1% per year. Although whites bear the highest incidence burden for most lymphoid neoplasm subtypes, most notably for hairy cell leukemia and follicular lymphoma, black predominance was observed for plasma cell and T-cell neoplasms. Asians have considerably lower rates than whites and blacks for CLL/SLL and Hodgkin lymphoma. We conclude that the striking differences in incidence patterns by histologic subtype strongly suggest that there is etiologic heterogeneity among lymphoid neoplasms and support the pursuit of epidemiologic analysis by subtype.
The paradox of response and survival in cancer therapeutics
Authors: Huff Carol Ann , Matsui William , Smith B. Douglas , Jones Richard J.
Published: September 2005

Although most patients with cancer respond to therapy, few are cured. Moreover, objective clinical responses to treatment often do not even translate into substantial improvements in overall survival. For example, patients with indolent lymphoma who achieved a complete remission with conventional-dose therapies in the prerituximab era did not experience a survival advantage over similar patients treated with a “watch and wait” approach. Several studies have also shown that neither the magnitude nor the kinetics of clinical response has an impact on survival in multiple myeloma. Recent data suggesting many malignancies arise from a rare population of cells that exclusively maintains the ability to self-renew and sustains the tumor (ie, “cancer stem cells”) may help explain this paradox that response and survival are not always linked. Therapies that successfully eliminate the differentiated cancer cells characterizing the tumor may be ineffective against rare, biologically distinct cancer stem cells. New methods for assessing treatment efficacy must also be developed, as traditional response criteria measure tumor bulk and may not reflect changes in rare cancer stem cell populations. In this article, we discuss the evidence for cancer stem cells in hematologic malignancies and possible ways to begin targeting these cells and measuring clinical effectiveness of such treatment approaches.
SUPERFICIAL – Surface mapping of proteins via structure-based peptide library design
Authors: Goede Andrean , Jaeger Ines S , Preissner Robert
Published: September 2005

Background

The determination of protein surfaces and the detection of binding sites are essential to our understanding of protein-protein interactions. Such binding sites can be characterised as linear and non-linear, the non-linear sites being prevailant. Conventional mapping techniques with arrays of synthetic peptides have limitations with regard to the location of discontinuous or non-linear binding sites of proteins.

Results

We present a structure-based approach to the design of peptide libraries that mimic the whole surface or a particular region of a protein. Neighbouring sequence segments are linked by short spacers to conserve local conformation. To this end, we have developed SUPERFICIAL, a program that uses protein structures as input and generates library proposals consisting of linear and non-linear peptides. This process can be influenced by a graphical user interface at different stages, from the surface computation up to the definition of spatial regions.

Conclusion

Based on 3D structures, SUPERFICIAL may help to negotiate some of the existing limitations, since binding sites consisting of several linear pieces can now be detected.
Comparison of theoretical proteomes: Identification of COGs with conserved and variable pI within the multimodal pI distribution
Authors: Nandi Soumyadeep , Mehra Nipun , Lynn Andrew M , Bhattacharya Alok
Published: September 2005

Background

Theoretical proteome analysis, generated by plotting theoretical isoelectric points (pI) against molecular masses of all proteins encoded by the genome show a multimodal distribution for pI. This multimodal distribution is an effect of allowed combinations of the charged amino acids, and not due to evolutionary causes. The variation in this distribution can be correlated to the organisms ecological niche. Contributions to this variation maybe mapped to individual proteins by studying the variation in pI of orthologs across microorganism genomes.

Results

The distribution of ortholog pI values showed trimodal distributions for all prokaryotic genomes analyzed, similar to whole proteome plots. Pairwise analysis of pI variation show that a few COGs are conserved within, but most vary between, the acidic and basic regions of the distribution, while molecular mass is more highly conserved. At the level of functional grouping of orthologs, five groups vary significantly from the population of orthologs, which is attributed to either conservation at the level of sequences or a bias for either positively or negatively charged residues contributing to the function. Individual COGs conserved in both the acidic and basic regions of the trimodal distribution are identified, and orthologs that best represent the variation in levels of the acidic and basic regions are listed.

Conclusion

The analysis of pI distribution by using orthologs provides a basis for resolution of theoretical proteome comparison at the level of individual proteins. Orthologs identified that significantly vary between the major acidic and basic regions maybe used as representative of the variation of the entire proteome.
Implementing evidence-based medicine in general practice: a focus group based study
Authors: Hannes Karin , Leys Marcus , Vermeire Etienne , Aertgeerts Bert , Buntinx Frank , Depoorter Anne-Marie
Published: September 2005

Background

Over the past years concerns are rising about the use of Evidence-Based Medicine (EBM) in health care. The calls for an increase in the practice of EBM, seem to be obstructed by many barriers preventing the implementation of evidence-based thinking and acting in general practice. This study aims to explore the barriers of Flemish GPs (General Practitioners) to the implementation of EBM in routine clinical work and to identify possible strategies for integrating EBM in daily work.

Methods

We used a qualitative research strategy to gather and analyse data. We organised focus groups between September 2002 and April 2003. The focus group data were analysed using a combined strategy of 'between-case' analysis and 'grounded theory approach'. Thirty-one general practitioners participated in four focus groups. Purposeful sampling was used to recruit participants.

Results

A basic classification model documents the influencing factors and actors on a micro-, meso- as well as macro-level. Patients, colleagues, competences, logistics and time were identified on the micro-level (the GPs' individual practice), commercial and consumer organisations on the meso-level (institutions, organisations) and health care policy, media and specific characteristics of evidence on the macro-level (policy level and international scientific community). Existing barriers and possible strategies to overcome these barriers were described.

Conclusion

In order to implement EBM in routine general practice, an integrated approach on different levels needs to be developed.
Comparison of air displacement plethysmography to hydrostatic weighing for estimating total body density in children
Authors: Claros Geo , Hull Holly R , Fields David A
Published: September 2005

Background

The purpose of this study was to examine the accuracy of total body density and percent body fat (% fat) using air displacement plethysmography (ADP) and hydrostatic weighing (HW) in children.

Methods

Sixty-six male and female subjects (40 males: 12.4 ± 1.3 yrs, 47.4 ± 14.8 kg, 155.4 ± 11.9 cm, 19.3 ± 4.1 kg/m2; 26 females: 12.0 ± 1.9 yrs, 41.4 ± 7.7 kg, 152.1 ± 8.9 cm, 17.7 ± 1.7 kg/m2) were tested using ADP and HW with ADP always preceding HW. Accuracy, precision, and bias were examined in ADP with HW serving as the criterion method. Lohman's equations that are child specific for age and gender were used to convert body density to % fat. Regression analysis determined the accuracy of ADP and potential bias between ADP and HW using Bland-Altman analysis.

Results

For the entire group (Y = 0.835x + 0.171, R2 = 0.84, SEE = 0.007 g/cm3) and for the males (Y = 0.837x + 0.174, R2 = 0.90, SEE = 0.006 g/cm3) the regression between total body density by HW and by ADP significantly deviated from the line of identity. However in females, the regression between total body density by HW and ADP did not significantly deviate from the line of identity (Y = 0.750x + 0.258, R2 = 0.55, SEE = 0.008 g/cm3). The regression between % fat by HW and ADP for the group (Y = 0.84x + 3.81, R2 = 0.83, SEE = 3.35 % fat) and for the males (Y = 0.84x + 3.25, R2 = 0.90, SEE = 3.00 % fat) significantly deviated from the line of identity. However, in females the regression between % fat by HW and ADP did not significantly deviate from the line of identity (Y = 0.81x + 5.17, R2 = 0.56, SEE = 3.80 % fat). Bland-Altman analysis revealed no bias between HW total body density and ADP total body density for the entire group (R = 0.-22; P = 0.08) or for females (R = 0.02; P = 0.92), however bias existed in males (R = -0.37; P ≤ 0.05). Bland-Altman analysis revealed no bias between HW and ADP % fat for the entire group (R = 0.21; P = 0.10) or in females (R = 0.10; P = 0.57), however bias was indicated for males by a significant correlation (R = 0.36; P ≤ 0.05), with ADP underestimating % fat at lower fat values and overestimating at the higher % fat values.

Conclusion

A significant difference in total body density and % fat was observed between ADP and HW in children 10–15 years old with a potential gender difference being detected. Upon further investigation it was revealed that the study was inadequately powered, thus we recommend that larger studies that are appropriately powered be conducted to better understand this potential gender difference.
Epigenetic inactivation and aberrant transcription of CSMD1 in squamous cell carcinoma cell lines
Authors: Richter Toni M , Tong Benton D , Scholnick Steven B
Published: September 2005

Background

The p23.2 region of human chromosome 8 is frequently deleted in several types of epithelial cancer and those deletions appear to be associated with poor prognosis. Cub and Sushi Multiple Domains 1 (CSMD1) was positionally cloned as a candidate for the 8p23 suppressor but point mutations in this gene are rare relative to the frequency of allelic loss. In an effort to identify alternative mechanisms of inactivation, we have characterized CSMD1 expression and epigenetic modifications in head and neck squamous cell carcinoma cell lines.

Results

Only one of the 20 cell lines examined appears to express a structurally normal CSMD1 transcript. The rest express transcripts which either lack internal exons, terminate abnormally or initiate at cryptic promoters. None of these truncated transcripts is predicted to encode a functional CSMD1 protein. Cell lines that express little or no CSMD1 RNA exhibit DNA methylation of a specific region of the CpG island surrounding CSMD1's first exon.

Conclusion

Correlating methylation patterns and expression suggests that it is modification of the genomic DNA preceding the first exon that is associated with gene silencing and that methylation of CpG dinucleotides further 3' does not contribute to inactivation of the gene. Taken together, the cell line data suggest that epigenetic silencing and aberrant splicing rather than point mutations may be contributing to the reduction in CSMD1 expression in squamous cancers. These mechanisms can now serve as a focus for further analysis of primary squamous cancers.
Tissue transglutaminase-induced alterations in extracellular matrix inhibit tumor invasion
Authors: Mangala Lingegowda S , Arun Banu , Sahin Aysegul A , Mehta Kapil
Published: September 2005

Background

Alterations in the extracellular matrix (ECM) can affect host-tumor interactions and tumor growth and metastasis. Tissue transglutaminase (TG2, EC 2.3.2.13), a calcium-dependent enzyme that catalyzes covalent cross-linking of proteins, can render the ECM highly stable and resistant to proteolytic degradation. So we determined whether TG2 expression in a tumor or nontumor (stroma) environment could affect the process of metastasis. Two hundred archived samples from patients with breast cancer were studied for the TG2 expression. Also, in an in vitro model the invasive behavior of MDA-MB-231 cells in the presence or absence of exogenous TG2 was determined.

Results

Tumors associated with negative nodes showed significantly higher expression of TG2 in the stroma (P < 0.001). TG2 in the stroma was catalytically active, as revealed by the presence of isopeptide cross-links. Pretreatment of Matrigel with catalytically active TG2 resulted in strong inhibition of invasion of MDA-MB-231 cells through the Matrigel Transwell filters.

Conclusion

TG2-induced alterations in the ECM could effectively inhibit the process of metastasis. Therefore, selective induction of catalytically active TG2 at the site of tumor may offer promising approach for limiting the metastasis.
A systematic evaluation of the quality of meta-analyses in the critical care literature
Authors: Delaney Anthony , Bagshaw Sean M , Ferland Andre , Manns Braden , Laupland Kevin B , Doig Christopher J
Published: September 2005

Introduction

Meta-analyses have been suggested to be the highest form of evidence available to clinicians to guide clinical practice in critical care. The purpose of this study was to systematically evaluate the quality of meta-analyses that address topics pertinent to critical care.

Methods

To identify potentially eligible meta-analyses for inclusion, a systematic search of Medline, EMBASE and the Cochrane Database of Systematic Reviews was undertaken, using broad search terms relevant to intensive care, including: intensive care, critical care, shock, resuscitation, inotropes and mechanical ventilation. Predetermined inclusion criteria were applied to each identified meta-analysis independently by two authors. To assess report quality, the included meta-analyses were assessed using the component and overall scores from the Overview Quality Assessment Questionnaire (OQAQ). The quality of reports published before and after the publication of the QUOROM statement was compared.

Results

A total of 139 reports of meta-analyses were included (kappa = 0.93). The overall quality of reports of meta-analyses was found to be poor, with an estimated mean overall OQAQ score of 3.3 (95% CI; 3.0–3.6). Only 43 (30.9%) were scored as having minimal or minor flaws (>5). We noted problems with the reporting of key characteristics of meta-analyses, such as performing a thorough literature search, avoidance of bias in the inclusion of studies and appropriately referring to the validity of the included studies. After the release of the QUOROM statement, however, an improvement in the overall quality of published meta-analyses was noted.

Conclusion

The overall quality of the reports of meta-analyses available to critical care physicians is poor. Physicians should critically evaluate these studies prior to considering applying the results of these studies in their clinical practice.
Brain Energetics and Tolerance to Anoxia in Deep Hypothermia
Authors: ANDJUS RADOSLAV K. , DŽAKULA ŽELJKO , MARKLEY JOHN L. , MACURA SLOBODAN
Published: September 2005

Abstract: The remarkable time‐resolution enhancement by deep lethargic hypothermia (15°C rectal temperature, “cold narcosis,”“anesthesia by internal cold”) of metabolic events in the rat brain after oxygen deprivation has been exploited to monitor metabolic changes by in vivo31P‐NMR. A correlation was established between the bioenergetic status of the brain and physiological descriptors of tolerance (survival and revival times) determined in parallel experiments with large series of animals. Spectral peak integrals were transformed into absolute concentrations by comparison to biochemically determined time series of data obtained in freeze‐trapping experiments conducted under identical conditions. Serial spectra were used to reconstruct the time‐course kinetics of intracellular brain pH and of concentration changes of inorganic phosphate, phosphocreatine, ATP, and ADP. Both the biochemical and NMR time series of data were simultaneously fitted by a set of exponential kinetic equations accounting for relationships imposed by the Lohmann and adenylate kinase reactions. Depletion profiles were then computed for a number of descriptors of brain energy status (energy charge, phosphorylation potential, total adenylate, and primary energy stores expressed as the sum of high‐energy phosphate‐bond equivalents). The results contribute to the understanding of the role of brain energetics in tolerance to oxygen deprivation.
Modeling of the Migration of the European Glass Eel
Authors: HEGEDIŠ ALEKSANDAR , KALAUZI ALEKSANDAR , MIĆKOVIĆ BRANISLAV , NIKČEVIĆ MIROSLAV , ANDJUS RADOSLAV K.
Published: September 2005

Abstract: The characteristics of glass eel migration at the mouth of river Bojana have been investigated by seasonal field studies from February to April 1998. Samples were collected by two fyke nets, one on each riverside, for 12 hours each night. A total of about 3,300 individuals were caught. In this work we present the results obtained from three successive migration waves in 1998. The data obtained on the number of eels caught during one migration wave, as a function of time, had two components: a bell‐shaped curve, lasting 7–14 days, over which an impulse (sudden burst in the number of caught eels, during 1–2 days) was observed. We propose a mathematical model for total number of captured eels within one migration wave. Impulse components were observed during the first and second migration waves. After their removal, the remaining experimental data of the three migration waves were fitted with normal distribution functions. A decrease in the values of fitting parameters as a function of time (migration wave number) was obtained. Our data indicate multiple causes for the observed migration waves.
Circadian Rhythmicity in AVP Secretion and GABAergic Synaptic Transmission in the Rat Suprachiasmatic Nucleus
Authors: KRETSCHMANNOVA KARLA , SVOBODOVA IRENA , BALIK ALES , MAZNA PETR , ZEMKOVA HANA
Published: September 2005

Abstract: A variety of physiological and behavioral functions exhibit circadian changes and these circadian rhythms are driven by oscillatory expression of clock genes in the suprachiasmatic nuclei (SCN). It is still unknown how this molecular clockwork is controlled by extracellular neurohormones and neurotransmitters and which membrane receptors undergo circadian modulation. Circadian rhythm can be measured as a secretion of arginine vasopressin (AVP) in organotypic SCN culture for several weeks. Melatonin applied directly to the SCN late in the day induces a phase advance, when applied late at night or at the beginning of the day melatonin causes a phase delay. The time window for phase advance corresponds with the highest level of melatonin receptors in the SCN but the mechanism of melatonin‐induced phase delay is unknown. The principal neurotransmitter on SCN synapses is γ‐aminobutyric acid (GABA), which acts at postsynaptic GABAA receptors. Spontaneous release of GABA from presynaptic nerve terminals, recorded as miniature inhibitory postsynaptic currents in the presence of TTX, does not change, but zinc sensitivity of exogenous GABA‐induced currents varies during the day and night, possibly due to changes in subunit composition of GABAA receptors. We conclude that there is daily variation in the postsynaptic, but not presynaptic, function in the SCN.
Molecular Dissection of Purinergic P2X Receptor Channels
Authors: STOJILKOVIC STANKO S. , TOMIĆ MELANIJA , HE MU‐LAN , YAN ZONGHE , KOSHIMIZU TAKA‐AKI , ZEMKOVA HANA
Published: September 2005

Abstract: The P2X receptors (P2XRs) are a family of ATP‐gated channels expressed in the plasma membrane of numerous excitable and nonexcitable cells and play important roles in control of cellular functions, such as neurotransmission, hormone secretion, transcriptional regulation, and protein synthesis. P2XRs are homomeric or heteromeric proteins, formed by assembly of at least three of seven subunits named P2X1‐P2X7. All subunits possess intracellular N‐ and C‐termini, two transmembrane domains, and a relatively large extracellular ligand‐binding loop. ATP binds to still an unidentified extracellular domain, leading to a sequence of conformational transitions between closed, open, and desensitized states. Removal of extracellular ATP leads to deactivation and resensitization of receptors. Activated P2XRs generate inward currents caused by Na+ and Ca2+ influx through the pore of channels, and thus mediate membrane depolarization and facilitation of voltage‐gated calcium entry in excitable cells. No crystal structures are available for P2XRs and these receptors have no obvious similarity to other ion channels or ATP binding proteins, which limits the progress in understanding the relationship between molecular structure and conformational transitions of receptor in the presence of agonist and after its washout. We summarize here the alternative approaches in studies on molecular properties of P2XRs, including heteromerization, chimerization, mutagenesis, and biochemical studies.