bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical risk conditions for acute lung injury in the intensive care unit and hospital ward: a prospective observational study
Authors: Ferguson Niall D , Frutos-Vivar Fernando , Esteban Andrés , Gordo Federico , Honrubia Teresa , Peñuelas Oscar , Algora Alejandro , García Gema , Bustos Alejandra , Rodríguez Inmaculada
Published: September 2007

Background

Little is known about the development of acute lung injury outside the intensive care unit. We set out to document the following: the association between predefined clinical conditions and the development of acute lung injury by using the American–European consensus definition; the frequency of lung injury development outside the intensive care unit; and the temporal relationship between antecedent clinical risk conditions, intensive care admission, and diagnosis of lung injury.

Methods

We conducted a 4-month prospective observational study in three Spanish teaching hospitals, enrolling consecutive patients who developed clinical conditions previously linked to lung injury, both inside and outside the intensive care unit. Patients were followed prospectively for outcomes, including the diagnosis of acute lung injury or acute respiratory distress syndrome.

Results

A total 815 patients were identified with at least one clinical insult; the most common were sepsis, pneumonia, and pancreatitis. Pulmonary risk conditions were observed in 30% of cases. Fifty-three patients (6.5%) developed acute lung injury; 33 of these (4.0%) met criteria for acute respiratory distress syndrome. Lung injury occurred most commonly in the setting of sepsis (46/53; 86.7%), but shock (21/59; 36%) and pneumonia (20/211; 9.5%) portended the highest proportional risk; this risk was higher in patients with increasing numbers of clinical risk conditions (2.2%, 14%, and 21% (P < 0.001) in patients with one, two, and three conditions, respectively). Median days (interquartile range) from risk condition to diagnosis of lung injury was shorter with pulmonary (0 (0 to 2)) versus extrapulmonary (3 (1 to 5)) (P = 0.029) risk conditions. Admission to the intensive care unit was provided to 9/20 (45%) patients with acute lung injury and to 29/33 (88%) of those with acute respiratory distress syndrome. Lung injury patients had higher mortality than others (acute lung injury 25.0%; acute respiratory distress syndrome 45.5%; others 10.3%; P < 0.001).

Conclusion

The time course from clinical insult to diagnosis of lung injury was rapid, but may be longer for extrapulmonary cases. Some patients with lung injury receive care and die outside the intensive care unit; this observation needs further study.
Functional constraint and small insertions and deletions in the ENCODE regions of the human genome
Authors: Clark Taane G , Andrew Toby , Cooper Gregory M , Margulies Elliott H , Mullikin James C , Balding David J
Published: September 2007

Background

We describe the distribution of indels in the 44 Encyclopedia of DNA Elements (ENCODE) regions (about 1% of the human genome) and evaluate the potential contributions of small insertion and deletion polymorphisms (indels) to human genetic variation. We relate indels to known genomic annotation features and measures of evolutionary constraint.

Results

Indel rates are observed to be reduced approximately 20-fold to 60-fold in exonic regions, 5-fold to 10-fold in sequence that exhibits high evolutionary constraint in mammals, and up to 2-fold in some classes of regulatory elements (for instance, formaldehyde assisted isolation of regulatory elements [FAIRE] and hypersensitive sites). In addition, some noncoding transcription and other chromatin mediated regulatory sites also have reduced indel rates. Overall indel rates for these data are estimated to be smaller than single nucleotide polymorphism (SNP) rates by a factor of approximately 2, with both rates measured as base pairs per 100 kilobases to facilitate comparison.

Conclusion

Indel rates exhibit a broadly similar distribution across genomic features compared with SNP density rates, with a reduction in rates in coding transcription and evolutionarily constrained sequence. However, unlike indels, SNP rates do not appear to be reduced in some noncoding functional sequences, such as pseudo-exons, and FAIRE and hypersensitive sites. We conclude that indel rates are greatly reduced in transcribed and evolutionarily constrained DNA, and discuss why indel (but not SNP) rates appear to be constrained at some regulatory sites.
Dynamic cumulative activity of transcription factors as a mechanism of quantitative gene regulation
Authors: He Feng , Buer Jan , Zeng An-Ping , Balling Rudi
Published: September 2007

Background

The regulation of genes in multicellular organisms is generally achieved through the combinatorial activity of different transcription factors. However, the quantitative mechanisms of how a combination of transcription factors controls the expression of their target genes remain unknown.

Results

By using the information on the yeast transcription network and high-resolution time-series data, the combinatorial expression profiles of regulators that best correlate with the expression of their target genes are identified. We demonstrate that a number of factors, particularly time-shifts among the different regulators as well as conversion efficiencies of transcription factor mRNAs into functional binding regulators, play a key role in the quantification of target gene expression. By quantifying and integrating these factors, we have found a highly significant correlation between the combinatorial time-series expression profile of regulators and their target gene expression in 67.1% of the 161 known yeast three-regulator motifs and in 32.9% of 544 two-regulator motifs. For network motifs involved in the cell cycle, these percentages are much higher. Furthermore, the results have been verified with a high consistency in a second independent set of time-series data. Additional support comes from the finding that a high percentage of motifs again show a significant correlation in time-series data from stress-response studies.

Conclusion

Our data strongly support the concept that dynamic cumulative regulation is a major principle of quantitative transcriptional control. The proposed concept might also apply to other organisms and could be relevant for a wide range of biotechnological applications in which quantitative gene regulation plays a role.
Metabolic peculiarities of Aspergillus niger disclosed by comparative metabolic genomics
Authors: Sun Jibin , Lu Xin , Rinas Ursula , Zeng An Ping
Published: September 2007

Background

Aspergillus niger is an important industrial microorganism for the production of both metabolites, such as citric acid, and proteins, such as fungal enzymes or heterologous proteins. Despite its extensive industrial applications, the genetic inventory of this fungus is only partially understood. The recently released genome sequence opens a new horizon for both scientific studies and biotechnological applications.

Results

Here, we present the first genome-scale metabolic network for A. niger and an in-depth genomic comparison of this species to seven other fungi to disclose its metabolic peculiarities. The raw genomic sequences of A. niger ATCC 9029 were first annotated. The reconstructed metabolic network is based on the annotation of two A. niger genomes, CBS 513.88 and ATCC 9029, including enzymes with 988 unique EC numbers, 2,443 reactions and 2,349 metabolites. More than 1,100 enzyme-coding genes are unique to A. niger in comparison to the other seven fungi. For example, we identified additional copies of genes such as those encoding alternative mitochondrial oxidoreductase and citrate synthase in A. niger, which might contribute to the high citric acid production efficiency of this species. Moreover, nine genes were identified as encoding enzymes with EC numbers exclusively found in A. niger, mostly involved in the biosynthesis of complex secondary metabolites and degradation of aromatic compounds.

Conclusion

The genome-level reconstruction of the metabolic network and genome-based metabolic comparison disclose peculiarities of A. niger highly relevant to its biotechnological applications and should contribute to future rational metabolic design and systems biology studies of this black mold and related species.
Transcriptomic and phenotypic analysis of murine embryonic stem cell derived BMP2+lineage cells: an insight into mesodermal patterning
Authors: Doss Michael Xavier , Chen Shuhua , Winkler Johannes , Hippler-Altenburg Rita , Odenthal Margareta , Wickenhauser Claudia , Balaraman Sridevi , Schulz Herbert , Hummel Oliver , Hübner Norbert , Ghosh-Choudhury Nandini , Sotiriadou Isaia , Hescheler Jürgen , Sachinidis Agapios
Published: September 2007

Background

Bone morphogenetic protein (BMP)2 is a late mesodermal marker expressed during vertebrate development and plays a crucial role in early embryonic development. The nature of the BMP2-expressing cells during the early stages of embryonic development, their transcriptome and cell phenotypes developed from these cells have not yet been characterized.

Results

We generated a transgenic BMP2 embryonic stem (ES) cell lineage expressing both puromycin acetyltransferase and enhanced green fluorescent protein (EGFP) driven by the BMP2 promoter. Puromycin resistant and EGFP positive BMP2+ cells with a purity of over 93% were isolated. Complete transcriptome analysis of BMP2+ cells in comparison to the undifferentiated ES cells and the control population from seven-day-old embryoid bodies (EBs; intersection of genes differentially expressed between undifferentiated ES cells and BMP2+ EBs as well as differentially expressed between seven-day-old control EBs and BMP2+ EBs by t-test, p < 0.01, fold change >2) by microarray analysis led to identification of 479 specifically upregulated and 193 downregulated transcripts. Transcription factors, apoptosis promoting factors and other signaling molecules involved in early embryonic development are mainly upregulated in BMP2+ cells. Long-term differentiation of the BMP2+ cells resulted in neural crest stem cells (NCSCs), smooth muscle cells, epithelial-like cells, neuronal-like cells, osteoblasts and monocytes. Interestingly, development of cardiomyocytes from the BMP2+ cells requires secondary EB formation.

Conclusion

This is the first study to identify the complete transcriptome of BMP2+ cells and cell phenotypes from a mesodermal origin, thus offering an insight into the role of BMP2+ cells during embryonic developmental processes in vivo.
How assessing reading comprehension with multiple-choice questions shapes the construct: a cognitive processing perspective
Authors: Rupp André A. , Ferne Tracy , Choi Hyeran
Published: August 2007

This article provides renewed converging empirical evidence for the hypothesis that asking test-takers to respond to text passages with multiple-choice questions induces response processes that are strikingly different from those that respondents would draw on when reading in non-testing contexts. Moreover, the article shows that the construct of reading comprehension is assessment specific and is fundamentally determined through item design and text selection. The data come from qualitative analyses of 10 cognitive interviews conducted with non-native adult English readers who were given three passages with several multiple-choice questions from the CanTEST, a large-scale language test used for admission and placement purposes in Canada, in a partially counter-balanced design. The analyses show that:

• There exist multiple different representations of the construct of ‘reading comprehension’ that are revealed through the characteristics of the items.

• Learners view responding to multiple-choice questions as a problem-solving task rather than a comprehension task.

• Learners select a variety of unconditional and conditional response strategies to deliberately select choices; and

• Learners combine a variety of mental resources interactively when determining an appropriate choice.

These findings support the development of response process models that are specific to different item types, the design of further experimental studies of test method effects on response processes, and the development of questionnaires that profile response processes and strategies specific to different item types.
Examining the relationship between differential item functioning and differential test functioning
Authors: Pae Tae-Il , Park Gi-Pyo
Published: August 2007

The present study utilized both the IRT-LR (item response theory likelihood ratio) and a series of CFA (confirmatory factor analysis) multi-sample analyses to systematically examine the relationships between DIF (differential item functioning) and DTF (differential test functioning) with a random sample of 15 000 Korean examinees. Specifically, DIF was detected using the IRT-LR method and the cumulative effect of DIF on DTF was gauged by the multi-sample analysis technique offered by the LISREL 8.5 program. The results of the current study indicate that item level DIF, once detected, may be carried to the test level bias regardless of the DIF directions, thereby showing mixed evidence to the previous findings reported in the literature. This suggests that the relation of DIF to DTF seems to be much more complex than that reported in the literature and, accordingly, more empirical studies are needed to bridge the gap in the literature about DIF-DTF relationships.
Treatment of victims of trauma
Authors: Adshead Gwen , Ferris Scott
Published: August 2007

Not all traumatic events cause post-traumatic stress disorder (PTSD), and people develop PTSD symptoms after events that do not seem to be overwhelmingly traumatic. In order to direct services appropriately, there is a need to distinguish time-limited post-traumatic symptoms and acute stress reactions (that may improve spontaneously without treatment or respond to discrete interventions) from PTSD, with its potentially more chronic pathway and possible long-term effects on the personality. In this article, we describe acute and chronic stress disorders and evidence about the most effective treatments.
Challenges in the treatment of dangerous and severe personality disorder
Authors: Howells Kevin , Krishnan Gopi , Daffern Michael
Published: August 2007

Dangerous and severe personality disorder (DSPD) services have a relatively short history but are increasingly involved in the implementation of therapeutic programmes. We describe the background to the DSPD initiative in England and consider issues that arise in planning and delivering treatment services. Two bodies of evidence are particularly relevant: previous research into personality disorder and its treatment, which we suggest is as yet of limited value, and research into the outcomes of offender treatment programmes. The latter is clearly relevant but greater consideration of adapting programmes for the patient population and of breadth of treatment is required in the DSPD setting. The important task is to integrate components for the treatment of personality disorder and offending behaviour in a holistic manner. We describe three further challenges in delivering treatment and suggest that ongoing evaluation of treatments is critical in this area of practice, given the impoverished knowledge base.
Post-traumatic stress disorder, resilience and vulnerability
Authors: Ahmed Ayesha S.
Published: August 2007

Post-traumatic stress disorder (PTSD), recognised as a diagnostic entity in 1980, was originally associated with combat or war experiences. It has since been recognised that it is prevalent in any population exposed to traumatic events. Although much has been written about the management of PTSD, the concepts of resilience and vulnerability have not received the same attention. This article reviews the conceptualisation, epidemiology and comorbidities of PTSD and highlights the factors underlying vulnerability and conveying resilience.
Controlling the confusion: management of referrals into mental health services for older adults
Authors: Colgate Robert , Jones Selina
Published: August 2007

This article describes the establishment of a clinician as a referral coordinator to manage referrals into a typical mental health service for older adults. The referral coordinator model, which include risk assessment at the point of referral and accurate comprehensive collection of referrer data, is compared with other traditional and more recent models of referral management. The importance of thorough collation of clinical information to produce a preliminary risk assessment and the stages of development of an algorithm as a core requirement to guide the coordinator and ensure consistency over time are described. An initial analysis of local referrer data and trends over a period of 3 years is presented to emphasise the educational opportunities offered by taking control of referral management.
Treatment of social phobia through pure self-help and therapist-augmented self-help
Authors: Rapee Ronald M. , Abbott Maree J. , Baillie Andrew J. , Gaston Jonathan E.
Published: August 2007

Background

Self-help for social phobia has not received controlled empirical evaluation.

Aims

To evaluate the efficacy of pure self-help through written materials for severe social phobia and self-help augmented by five group sessions with a therapist. These conditions were compared with a waiting-list control and standard, therapist-led group therapy.

Method

Participants with severe generalised social phobia (n=224) were randomised to one of four conditions. Assessment included diagnoses, symptoms and life interference at pretreatment, 12 weeks and at 24 weeks.

Results

A larger percentage of patients no longer had a diagnosis of social phobia at post-intervention in the pure self-help group than in the waiting-list group, although this percentage decreased slightly over the next 3 months. Symptoms of social anxiety and life interference did not differ significantly between these groups. Augmented self-help was better than waiting list on all measures and did not differ significantly from group treatment.

Conclusions

Self-help augmented by therapist assistance shows promise as a less resource-intensive method for the management of social phobia. Pure self-help shows limited efficacy for this disorder.
Sulcal thickness as a vulnerability indicator for schizophrenia
Authors: Goghari Vina M. , Rehm Kelly , Carter Cameron S. , Macdonald Angus W.
Published: August 2007

Background

People with schizophrenia may demonstrate cortical abnormalities, with gyri and sulci potentially being differentially affected.

Aims

To measure frontal and temporal sulcal cortical thickness, surface area and volume in the non-psychotic relatives of patients with schizophrenia as a potential vulnerability indicator for the disorder.

Method

An automated parcellation method was used to measure the superior frontal, inferior frontal, cingulate, superior temporal and inferior temporal sulci in the relatives of patients (n=19) and controls (n=22).

Results

Compared with controls, relatives had reversed hemispheric asymmetry in their cingulate sulcal thickness and a bilateral reduction in their superior temporal sulcal thickness.

Conclusions

Cingulate and superior temporal sulcal thickness abnormalities may reflect neural abnormalities associated with the genetic liability to schizophrenia. Cortical thinning in these regions suggests that liability genes affect the dendrites, synapses or myelination process during the neurodevelopment of the cortical mantle.
Women with autistic-spectrum disorder: magnetic resonance imaging study of brain anatomy
Authors: Craig Michaelc. , Zaman Shahid H. , Daly Eileen M. , Cutter William J. , Robertson Dene M. W. , Hallahan Brian , Toal Fiona , Reed Suzie , Ambikapathy Anita , Brammer Mick , Murphy Clodagh M. , Murphy Declan G. M.
Published: August 2007

Background

Our understanding of anatomical differences in people with autistic-spectrum disorder, is based on mixed-gender or male samples.

Aims

To study regional grey-matter and white-matter differences in the brains of women with autistic-spectrum disorder.

Method

We compared the brain anatomy of 14 adult women with autistic-spectrum disorder with 19 controls using volumetric magnetic resonance imaging and voxel-based morphometry Results Women with autistic-spectrum disorder had a smaller density bilaterally of grey matter in the frontotemporal cortices and limbic system, and of white matter in the temporal lobes (anterior) and pons. In contrast, they had a larger white-matter density bilaterally in regions of the association and projection fibres of the frontal, parietal, posterior temporal and occipital lobes, in the commissural fibres of the corpus callosum (splenium) and cerebellum (anterior lobe). Further, we found a negative relationship between reduced grey-matter density in right limbic regions and social communication ability.

Conclusions

Women with autistic-spectrum disorder have significant differences in brain anatomy from controls, in brain regions previously reported as abnormal in adult men with the disorder. Some anatomical differences may be related to clinical symptoms.
Ten books
Authors: King Michael
Published: August 2007

Choosing ten books that have most influenced my practice is an odd challenge. I wasn't one of those medical students who wanted to do psychiatry since he was 12, or read most of Freud or Jung. In fact throughout medical school, and for several years as a junior doctor, I thought psychiatry and psychiatrists were pretty weird. It was only in my general practice vocational training year that I realised how much of medicine concerned the psychological and began my psychiatric training. This influence came not through books that I read but through the patients whom I saw.
Insight, psychopathology and global functioning in schizophrenia in urban Malawi
Authors: Crumlish Niall , Samalani Prince , Sefasi Anthony , Kinsella Anthony , O'Callaghan Eadbhard , Chilale Harris
Published: August 2007

Insight, psychopathology and functioning are related in schizophrenia, but it is unclear whether insight relates independently to functioning after controlling for psychopathology. Equally, any such relationship may vary culturally. We investigated the relationship between insight, psychopathology and functioning in 60 patients with schizophrenia in Mzuzu, a town in Malawi. After controlling for psychopathology, functioning was associated with the ‘symptom relabelling’ dimension of insight (P=0.01). This preliminary finding suggests that symptom-focused psychoeducation might be appropriate for African patients with schizophrenia.
Inter-examiner reliability of the clinical parts of MRCPsych part II examinations
Authors: Oyebode Femi , George Sanju , Math Veena , Haque Sayeed
Published: August 2007

Aims and Method

The aim of the study was to investigate the interrater reliability of the clinical component of the MRCPsych part II examinations, namely the individual patient assessment and the patient management problems. In the study period, there were 1546 candidates and 773 pairs of examiners. Kappa scores for pairs of examiners in both these assessments were calculated.

Results

The kappa scores for exact numerical agreement between the pairs of examiners in both individual patient assessment and patient management problems were only moderate (0.4 –0.5). However, the kappa scores for agreement between pairs of examiners for the reclassified pass and fail categories were very good (0.8).

Clinical Implications

The poor reliability of the traditional long case and oral examinations in general is one of the most potent arguments against their use. Our finding suggests that the College clinical examinations are at least not problematic from this point of view, particularly if global pass or fail judgements rather than discrete scores are applied.
Validation of the Social Satisfaction Questionnaire for outcome evaluation in substance use disorders
Authors: Raistrick Duncan , Tober Gillian , Heather Nick , Clark Jennifer A.
Published: August 2007

Aims and Method

To develop a scale to measure social satisfaction in people with substance use disorders and to test its psychometric properties. The rationale is that social satisfaction is more universal and relevant to treatment planning than assessing social problems. The new Social Satisfaction Questionnaire (SSQ) was derived from an existing social problems questionnaire and validation was undertaken on two large clinic populations.

Results

An eight-item SSQ was tested and found to have good psychometric properties in terms of test–retest reliability, internal consistency, distribution of responses and concurrent validity.

Clinical Implications

The SSQ is suitable for use as the social domain element of an outcome measures package.
Nepalese psychiatrists' struggle for evolution
Authors: Jha Arun
Published: August 2007

Nepal has a short and slowly developing history of psychiatry. Recent political turmoil has crippled Nepalese healthcare in rural areas. Although the final quarter of the 20th century saw some development of psychiatric services in Nepal, the majority of Nepalese people remain deprived of such services even today. There is no national health programme or Mental Health Act. Psychiatric services are hospital based and most are centralised in the capital. Nepalese psychiatrists need urgent help, but they have been unable to form a strong professional body. This report presents the historical background, current state of affairs and suggestions for modernising mental health services in Nepal.
Lipocalin‐2, TWEAK, and Other Cytokines as Urinary Biomarkers for Lupus Nephritis
Authors: SCHWARTZ NOA , MICHAELSON JENNIFER S. , PUTTERMAN CHAIM
Published: September 2007

Abstract:  Lupus nephritis (LN) is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). As the course of LN is often unpredictable, it is important to identify reliable, noninvasive methods to repeatedly assess the condition of the kidneys in these patients. Urinary biomarkers are easily obtained and probably are best at reflecting the current renal status, as they specifically represent local inflammatory activity. In this article, we review a number of potential urinary biomarkers, including Lipocalin‐2, MCP‐1, IP‐10, IL‐6, and IL‐8. Additionally, we provide evidence for the possible utility of the novel cytokine TWEAK as a urinary biomarker for LN.
Evaluation of the LIAISON ANA Screen Assay for Antinuclear Antibody Testing in Autoimmune Diseases
Authors: GHILLANI P. , ROUQUETTE A. M. , DESGRUELLES C. , HAUGUEL N. , LE PENDEVEN C. , PIETTE J. C. , MUSSET L.
Published: September 2007

Abstract:  Antinuclear antibodies (ANA) are widely detected by immunofluorescence on HEp‐2 cells in patients with connective tissue diseases and other pathological conditions. We evaluated the first‐automated chemiluminescence immunoassay for the detection of ANA (LIAISON ANA screen, DiaSorin). This study was carried out simultaneously in two laboratories by testing 327 patient samples with clinically defined connective diseases, 273 routine samples for ANA screening, and 300 blood donors. A total of 268 out of 337 IIF‐positive sera were positive with LIAISON ANA screen (79.5% of agreement) and 240 out of 263 IIF‐negative sera were negative with LIAISON ANA screen (91.2% of agreement). After resolution of discrepant results, the concordance reached, respectively, 94.9% and 98.8%. The specificity was 99.3% and the sensitivity was 94%. Unlike results obtained by other ANA screening assays, we observed acceptable sensitivity and specificity. Despite the presence of HEp‐2 cell extract, we failed to detect some antibodies as antinucleolar, antinuclear envelope, and antiproliferating cell nuclear antigen. This automated assay allows quick process to results and exhibits satisfactory sensitivity for the detection of the main ANA specificities of connective tissue diseases.
Chemokine Profile of Different Inflammatory Myopathies Reflects Humoral versus Cytotoxic Immune Responses
Authors: De PAEPE BOEL , CREUS KIM K. , De BLEECKER JAN L.
Published: September 2007

Abstract:  The idiopathic inflammatory myopathies (IM) are subdivided into dermatomyositis (DM), polymyositis (PM), and sporadic inclusion body myositis (IBM). These autoimmune muscle diseases represent different immunopathological entities. DM is a humoral endotheliopathy initiated by complement deposition in intramuscular blood vessels, and characterized by perimysial inflammation and muscle fiber atrophy in perifascicular regions. In PM and IBM, nonnecrotic muscle fibers are actively invaded by autoaggressive macrophages and cytotoxic T cells. Chemokines are key mediators of inflammatory disease as they regulate leukocyte recruitment to tissue target sites. We studied a large selection of α/β‐chemokines and receptors in normal controls and in the IM using immunohistochemistry, immunofluorescence, in situ hybridization, and Western blotting. We showed that the chemokine array of normal myocytes was limited, while the blood vessels in normal skeletal muscle tissue displayed a broad chemokine profile. The IM were characterized by a general increase of specific chemokines and chemokine receptors, while chemokine distribution reflected the two different immune responses represented within these muscle diseases. In DM, endothelial expression of CCL2 and CXCL12β was highly increased. In PM and IBM, macrophages and cytotoxic T cells actively invading nonnecrotic muscle fibers expressed highest levels of CXCL10 and CCL2. Some chemokines were selectively expressed by different IM infiltrates: CCL4 was present only in the perimysial inflammatory foci of a subset of DM biopsies, while CXCL1, CXCL2, CXCL3, and CCL7‐positive cells were exclusively detected in endomysial infiltrates of a number of PM and IBM samples. The chemokine receptor profile of the IM indicated the predominance of Th1‐mediated immune responses in all three IM. Our studies identified three ligand‐receptor pairs, namely CXCL10/CXCR3, CXCL12/CXCR4, and CCL2/CCR2, as potential targets for chemokine‐based therapy in IM.
Anti‐Vitamin D, Vitamin D in SLE
Authors: CARVALHO JOZÉLIO FREIRE , BLANK MIRI , KISS EMESE , TARR TUNDE , AMITAL HOWARD , SHOENFELD YEHUDA
Published: September 2007

Abstract:  The aim of this study was to detect antibodies to vitamin D in systemic lupus erythematosus (SLE) and other autoimmune diseases. The results may shed light to a novel aspect of vitamin D deficiency in autoimmune diseases. Sera from 171 patients with SLE, 56 with antiphospholipid syndrome (APS), and 18 with pemphigus vulgaris (PV) were studied employing an enzyme‐linked immunosorbent assay for anti‐vitamin D antibodies along with 94 healthy blood donors. In parallel, vitamin D concentrations in the serum were determined by a DiaSorin commercial kit (LIAISON 25 OH vitamin D). Antibody‐positive and antibody‐negative individuals were compared with respect to demographic variables, SLE disease activity index (SLEDAI) score, autoantibodies profile, and serum vitamin D levels. Anti‐vitamin D antibodies were detected in 7 (4%) of 171 patients with SLE, in 2 (3.5%) of 56 of sera from patients with APS, and in 2 (11%) of 18 sera from patients with PV. Vitamin D levels were similar in both SLE groups with and without anti‐vitamin D antibodies. Demographic features, organ involvement, SLEDAI score, and autoantibodies did not differ between the groups. Except for anti‐dsDNA antibodies, in which anti‐vitamin D antibodies were strongly associated with these antibodies in sera from SLE patients (P= 0.0004). Anti‐vitamin D antibodies are observed in a subset of patients with SLE, APS, and PV, and are associated with anti‐dsDNA antibodies in SLE. Further studies are required to explore the potential diagnostic and prognostic role of these novel antibodies in SLE.
The Glucose Transporter 4 FQQI Motif Is Necessary for Akt Substrate of 160-Kilodalton-Dependent Plasma Membrane Translocation But Not Golgi-Localized γ-Ear-Containing Arf-Binding Protein-Dependent Entry into the Insulin-Responsive Storage Compartment
Authors: Capilla Encarnación , Suzuki Naoko , Pessin Jeffrey E. , Hou June Chunqiu
Published: August 2007

Newly synthesized glucose transporter 4 (GLUT4) enters into the insulin-responsive storage compartment in a process that is Golgi-localized γ-ear-containing Arf-binding protein (GGA) dependent, whereas insulin-stimulated translocation is regulated by Akt substrate of 160 kDa (AS160). In the present study, using a variety of GLUT4/GLUT1 chimeras, we have analyzed the specific motifs of GLUT4 that are important for GGA and AS160 regulation of GLUT4 trafficking. Substitution of the amino terminus and the large intracellular loop of GLUT4 into GLUT1 (chimera 1-441) fully recapitulated the basal state retention, insulin-stimulated translocation, and GGA and AS160 sensitivity of wild-type GLUT4 (GLUT4-WT). GLUT4 point mutation (GLUT4-F5A) resulted in loss of GLUT4 intracellular retention in the basal state when coexpressed with both wild-type GGA and AS160. Nevertheless, similar to GLUT4-WT, the insulin-stimulated plasma membrane localization of GLUT4-F5A was significantly inhibited by coexpression of dominant-interfering GGA. In addition, coexpression with a dominant-interfering AS160 (AS160-4P) abolished insulin-stimulated GLUT4-WT but not GLUT4-F5A translocation. GLUT4 endocytosis and intracellular sequestration also required both the amino terminus and large cytoplasmic loop of GLUT4. Furthermore, both the FQQI and the SLL motifs participate in the initial endocytosis from the plasma membrane; however, once internalized, unlike the FQQI motif, the SLL motif is not responsible for intracellular recycling of GLUT4 back to the specialized compartment. Together, we have demonstrated that the FQQI motif within the amino terminus of GLUT4 is essential for GLUT4 endocytosis and AS160-dependent intracellular retention but not for the GGA-dependent sorting of GLUT4 into the insulin-responsive storage compartment.
How Does Free Riding on Customer Service Affect Competition?
Authors: Shin Jiwoong
Published: September 2007

The free-riding problem occurs if the presales activities needed to sell a product can be conducted separately from the actual sale of the product. Intuitively, free riding should hurt the retailer that provides that service, but the author shows analytically that free riding benefits not only the free-riding retailer, but also the retailer that provides the service when customers are heterogeneous in terms of their opportunity costs for shopping. The service-providing retailer has a postservice advantage, because customers who have resolved their matching uncertainty through sales service incur zero marginal shopping cost if they purchase from the service-providing retailer rather than the free-riding retailer. Moreover, allowing free riding gives the free rider less incentive to compete with the service provider on price, because many customers eventually will switch to it due to their own free riding. In turn, this induced soft strategic response enables the service provider to charge a higher price and enjoy the strictly positive profit that otherwise would have been wiped away by head-to-head price competition. Therefore, allowing free riding can be regarded as a necessary mechanism that prevents an aggressive response from another retailer and reduces the intensity of price competition.
Assessment of mobility after multi-level surgery for cerebral palsy
Authors: Graham H. K. , Harvey A.
Published: September 2007

In cerebral palsy, the site and severity of the brain lesion are directly linked to gross motor function and the development of musculoskeletal deformities. The relationship between walking ability and orthopaedic surgery in children with cerebral palsy is not fully understood. The development of new tools such as the Functional Assessment Questionnaire and the Functional Mobility Scale can be used to give new insights on the functional impact of multilevel surgery. These scales are most useful as part of systematic, long-term follow-up.
Maggot Debridement Therapy of Infected Ulcers: Patient and Wound Factors Influencing Outcome – A Study on 101 Patients with 117 Wounds
Authors: Steenvoorde Pascal , Jacobi Cathrien E , Van Doorn Louk , Oskam Jacques
Published: August 2007

INTRODUCTION

It has been known for centuries that maggots are potent debriding agents capable of removing necrotic tissue and slough. In January 2004, the US Food and Drug Administration decided to regulate maggot debridement therapy (MDT). As it is still not clear which wounds are likely or unlikely to benefit from MDT, we performed a prospective study to gain more insight in patient and wound characteristics influencing outcome.

PATIENTS AND METHODS

In the period between August 2002 and December 2005, patients with infected wounds with signs of gangrenous or necrotic tissue who seemed suited for MDT were enrolled in the present study. In total, 101 patients with 117 ulcers were treated. Most wounds were worst-case scenarios, in which maggot therapy was a treatment of last resort.

RESULTS

In total, 72 patients (71%) were classified as ASA III or IV. In total, 78 of 116 wounds (67%) had a successful outcome. These wounds healed completely (n = 60), healed almost completely (n = 12) or were clean at least (n = 6) at last follow-up. These results seem to be in line with those in the literature. All wounds with a traumatic origin (n = 24) healed completely. All wounds with septic arthritis (n = 13), however, failed to heal and led in half of these cases to a major amputation. According to a multivariate analysis, chronic limb ischaemia (odds ratio [OR], 7.5), the depth of the wound (OR, 14.0), and older age (≥ 60 years; OR, 7.3) negatively influenced outcome. Outcome was not influenced by gender, obesity, diabetes mellitus, smoking, ASAclassification, location of the wound, wound size or wound duration.

CONCLUSIONS

Some patient characteristics (i.e. gender, obesity, smoking behaviour, presence of diabetes mellitus and ASA-classification at presentation) and some wound characteristics (i.e. location of the wound, wound duration and size) do not seem to contra-indicate eligibility for MDT. However, older patients and patients with chronic limb ischaemia or deep wounds are less likely to benefit from MDT. Septic arthritis does not seem to be a good indication for MDT.
Manipulating autonomy, competence, and relatedness support in a game‐learning context: New evidence that all three needs matter
Authors: Sheldon Kennon M. , Filak Vincent
Published: August 2007

Self‐report correlational data support self‐determination theory's (SDT's) postulate that there are three basic psychological needs, for autonomy, competence, and relatedness, which combine additively to predict well‐being and thriving. However, experimental research in the SDT tradition has focused only on autonomy support, not relatedness and competence support. To fill this gap, we employed a 2 × 2×2 factorial design within a game‐learning experience to predict rated need satisfaction, mood, and motivation, and also objective game performance. Manipulated competence and relatedness support had main effects on most outcomes. Rated competence, relatedness, and autonomy need satisfaction also predicted the outcomes, and the significant experimental main effects were all mediated by the corresponding rated variables. Neutral control group data showed that thwarting participants' needs is more impactful than enhancing them. These findings offer new support for key postulates of SDT, while integrating the correlational and experimental traditions in this area.
But What Does it Mean? Seeking Definitional Clarity in Restorative Justice
Authors: Doolin Katherine
Published: September 2007

This article examines, considers the effects of, and proposes resolutions to a number of significant tensions arising from the way the fundamental concepts of restorative justice are defined and used. The article uses as a framework two key issues. First, whether restorative justice should be defined primarily in terms of the process to be used or the outcomes to be achieved. Secondly, attention will be drawn to the lack of clarity in defining restoration. This article proposes a list of irreducible core values of restorative justice and contends that agreement about these will best advance the theoretical debate, assist the appraisal of restorative justice in practice and prioritise the restoration of victims and the fair treatment of offenders.
Correlation of Obesity and Osteoporosis: Effect of Fat Mass on the Determination of Osteoporosis
Authors: Zhao Lan-Juan , Jiang Hui , Papasian Christopher J , Maulik Dev , Drees Betty , Hamilton James , Deng Hong-Wen
Published: September 2007

It was previously believed that obesity and osteoporosis were two unrelated diseases, but recent studies have shown that both diseases share several common genetic and environmental factors. Body fat mass, a component of body weight, is one of the most important indices of obesity, and a substantial body of evidence indicates that fat mass may have beneficial effects on bone. Contrasting studies, however, suggest that excessive fat mass may not protect against osteoporosis or osteoporotic fracture. Differences in experimental design, sample structure, and even the selection of covariates may account for some of these inconsistent or contradictory results. Despite the lack of a clear consensus regarding the impact of effects of fat on bone, a number of mechanistic explanations have been proposed to support the observed epidemiologic and physiologic associations between fat and bone. The common precursor stem cell that leads to the differentiation of both adipocytes and osteoblasts, as well the secretion of adipocyte-derived hormones that affect bone development, may partially explain these associations. Based on our current state of knowledge, it is unclear whether fat has beneficial effects on bone. We anticipate that this will be an active and fruitful focus of research in the coming years.
A New Slurry-Based Method of Preparation of Specimens of Sand Containing Fines
Authors: Carraro J. Antonio H. , Prezzi Monica
Published: September 2007

A new method of specimen reconstitution is presented that is appropriate for element testing of sands containing either plastic or nonplastic fines. The method allows reconstitution of homogeneous, saturated specimens of sands containing fines whose stress-strain response closely resembles the stress-strain response of natural soil deposits formed underwater (e.g., alluvial and offshore submarine deposits, hydraulic fills, and tailings dams). A procedure is described to evaluate the maximum void ratio (emax) of sands containing fines under conditions that more appropriately represent soil deposition at its loosest state in aquatic environments. For soils deposited in water, the data obtained with the procedure proposed in this paper suggest that ASTM D 4254 overestimates the emax of sands containing plastic fines and underestimates the emax of sands containing nonplastic fines.
Circulating nerve growth factor levels in relation to obesity and the metabolic syndrome in women
Authors: Bulló Mònica , Peeraully Muhammad R , Trayhurn Paul , Folch J , Salas-Salvadó Jordi
Published: August 2007

Objective: Neurotrophins (NTs) could be involved in the development and progression of inflammatory and immune diseases. Because obesity and the metabolic syndrome (MetSyn) are related to a low-grade systemic inflammation, plasma NT levels (neurotrophinemia) could play an important role in the ethiopathogenic mechanisms underlying these metabolic derangements. This is the first study evaluating the plasma NT levels in a group of women with obesity and MetSyn, and also the adipose tissue nerve growth factor (NGF) expression in a small group of them.

Methods: Included were 146 adult women with different degrees of adiposity, with or without MetSyn. Plasma NT levels were measured. NGF expression was analyzed in s.c. adipose tissue of a subgroup of morbidly obese and normal-weight females.

Results: NGF plasma levels were 1.4-fold higher in overweight and obese subjects. Plasma NGF was, however, lower in a group of morbidly obese subjects than in overweight or obesity, but it remained elevated relative to the normal-weight group. Plasma NGF was significantly correlated with body mass index (BMI), percentage body fat, and waist circumference in non-morbidly obese subjects. NGF was positively related to inflammatory markers. NT3 and brain-derived neurotrophin factor seem to be more related to lipid profile than to BMI, adipose tissue distribution, or peripheral inflammatory markers. Subjects with type 2 diabetes, abdominal fat distribution, or the MetSyn showed significantly higher levels of NGF. The MetSyn was the only independent predictor of the variability observed in the NGF plasma values.

Conclusion: NGF is upregulated in obesity, type 2 diabetes, and the MetSyn. Whether this NT may contribute to inflammation and the metabolic derangements associated with body weight gain remains to be elucidated.
Recent outcome of Graves’ disease patients with papillary thyroid cancer
Authors: Yano Yukiko , Shibuya Hiroshi , Kitagawa Wataru , Nagahama Mitsuji , Sugino Kiminori , Ito Kunihiko , Ito Koichi
Published: August 2007

Objective: The objective was to evaluate the clinical behavior and outcome of 202 papillary thyroid cancers in Graves’ disease patients during the period 1994–2004.

Design: This was a retrospective, non-randomized case–control study.

Methods: Since 1994, we have included an ultrasonogram of the neck in the initial examination of thyroid disease patients who consult our outpatient clinic. We evaluated the tumor status and long-term outcome of Graves’ disease patients with thyroid cancer and of age- and tumor size-matched euthyroid papillary thyroid cancer patients as controls. Serum TSH receptor antibody (TRAb) was measured in the Graves’ disease group.

Results: A total of 154 papillary thyroid cancers were diagnosed in the Graves’ disease patients and were treated surgically. At surgery, no significant differences in multifocality, lymph node metastasis, or distant metastasis were found between the Graves’ disease group and the euthyroid group. On the whole, the clinical course of the cancers in both the Graves’ disease group and euthyroid group was relatively good. No significant correlations were found between the TRAb levels in the Graves’ disease group and multifocality or the presence of lymph node metastasis. Papillary thyroid cancer was discovered as an incidental finding in 2% of the 2356 surgically treated Graves’ disease patients, but none of them developed metastasis during the follow-up period.

Conclusion: The results in this series of patients do not support the claim that thyroid cancer is more aggressive in Graves’ disease patients than in euthyroid patients.