bluuebunny/crossref_metadata_2025 huggingface dataset:
Contemporary Pharmacologic Issues in the Management of Traumatic Brain Injury
Authors: Gross A. Kendall , Norman Joel , Cook Aaron M.
Published: June 2010

Traumatic brain injury (TBI) is a major cause of death and disability in the United States. While there are no pharmacotherapeutic options currently available for attenuating the neurologic injury cascade after TBI, numerous pharmacologic issues are encountered in these critically ill patients. Adequate fluid resuscitation, reversal of coagulopathy, maintenance of cerebral perfusion, and treatment of intracranial hypertension are common interventions early in the treatment of TBI. Other deleterious complications such as venous thromboembolism, extremes in glucose concentrations, and stress-related mucosal disease should be anticipated and avoided. Early provision of nutrition and prevention of drug or alcohol withdrawal are also cornerstones of routine care in TBI patients. Prevention of infections and seizures may also be helpful. Clinicians caring for TBI patients should be familiar with the pharmacologic issues typical of this vulnerable population in order to develop optimal strategies of care to anticipate and prevent common complications.
Acne rosacea associated imatinib mesylate in a gastrointestinal stromal tumor patient
Authors: Demirci Umut , Coskun Ugur , Erdem Ozlem , Ozturk Banu , Bilge Yilmaz Isilay , Benekli Mustafa , Buyukberber Suleyman
Published: June 2010

Tyrosine kinase inhibitors (TKIs) are targeted treatments for various cancers. Skin toxicities are one of the most common nonhematological side-effects of TKIs. We report an imatinib mesylate (IM) induced hyperpigmented acne rosacea (AR) and sunitinib-induced palmar hyperkeratosis in the case with gastrointestinal stromal tumor. AR was arisen due to the discontinuation of IM. To the best of our knowledge, this kind of cutaneous side-effect with IM has not been documented previously.
Infanticide and Neonaticide: A Review of 40 Years of Research Literature on Incidence and Causes
Authors: Porter Theresa , Gavin Helen
Published: June 2010

The prevailing public view on women who kill their babies is that they are either monsters or psychotic, or both. The psychiatric and legal communities recognize that the issue is not as simply dichotomous as this. Evidence suggests that there are important distinctions to be drawn between different types of baby deaths and that this may have implications for identification, punishment, and/or treatment of potential and actual perpetrators. This article reviews and summarizes research, incidence statistics, and judicial and clinical outcomes ranging over four decades of work and sets out various ways forward in the study and prevention of infant murder.
Outreach, Engagement, and Practical Assistance: Essential Aspects of PTSD Care for Urban Victims of Violent Crime
Authors: Kelly Vanessa G. , Merrill Gregory S. , Shumway Martha , Alvidrez Jennifer , Boccellari Alicia
Published: June 2010

The purpose of this article is to examine the literature on the increased risk factors of disadvantaged inner-city residents for becoming victims of violence and for developing posttraumatic stress disorder (PTSD) and barriers to accessing comprehensive mental health services. Second, the article discusses the limitations of evidence-based treatments for early intervention with urban victims of violence and provides a new model of care emphasizing outreach, engagement, and practical assistance. Finally, the article concludes with recommendations for comprehensive hospital-based urban programs in terms of practice, policy, and research.
Spontaneous Thrombosis of Congenital Extrahepatic Portosystemic Shunt (Abernethy Malformation) Simulating Inguinal Hernia Incarceration
Authors: Afzal Samara , Nair Amit , Grainger Jennie , Latif Sherif , Rehman Atiq-ur
Published: June 2010

Tender lumps in the inguinal region are often explored emergently to treat suspected hernial strangulation. We discuss the case of an adult male who presented acutely with a tender inguinal swelling and raised inflammatory markers and was therefore deemed as requiring surgical exploration. However preoperative abdominal computerized tomography (CT) revealed an extensive thrombosing congenital venous malformation of portosystemic origin with extension into the symptomatic inguinal canal. A potentially lethal exsanguination from surgery was thus avoided.
The bacterial pathogenesis and treatment of pouchitis
Authors: McLaughlin S.D. , Clark S.K. , Tekkis P.P. , Nicholls R.J. , Ciclitira P.J.
Published: June 2010

Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis is the operation of choice for patients with ulcerative colitis. Pouchitis is the most common cause of pouch dysfunction. Although the pathogenesis of this disease is not well understood, bacteria have been implicated in the disease process. Numerous bacterial studies have been reported over the last 25 years with few unifying findings. In addition, many different treatments for pouchitis have been reported with varying results. Antibiotic treatment remains the most studied and is the mainstay of treatment. In this article we review the aetiology of pouchitis and the evidenced-based treatment options.
Potential Benefits of Parenteral Fish Oil Lipid Emulsions in Parenteral Nutrition-Associated Liver Disease
Authors: Gura Kathleen M.
Published: June 2010

The etiology of parenteral nutrition—associated liver disease (PNALD) is complex and multifactorial. Recent evidence suggests that the composition of the intravenous lipid emulsion, which is typically administered as part of parenteral nutrition to provide dense calories and prevent essential fatty acid deficiency, can significantly contribute to PNALD. Since September 2004, Children’s Hospital Boston has been treating patients with PNALD by stopping the conventional soy oil—based emulsions and using one that is composed solely of fish oils. Despite favorable outcomes, concerns about the use of fish oil as monotherapy continue to be raised because of the perceived risks of increased bleeding and essential fatty acid deficiency. This review discusses the published evidence to date describing the efficacy of this novel therapy in the treatment of an often fatal complication of parenteral nutrition use.
Discovery of novel mechanosensitive genes in vivo using mouse carotid artery endothelium exposed to disturbed flow
Authors: Ni Chih-Wen , Qiu Haiwei , Rezvan Amir , Kwon Kihwan , Nam Douglas , Son Dong Ju , Visvader Jane E. , Jo Hanjoong
Published: June 2010

Recently, we showed that disturbed flow caused by a partial ligation of mouse carotid artery rapidly induces atherosclerosis. Here, we identified mechanosensitive genes in vivo through a genome-wide microarray study using mouse endothelial RNAs isolated from the flow-disturbed left and the undisturbed right common carotid artery. We found 62 and 523 genes that changed significantly by 12 hours and 48 hours after ligation, respectively. The results were validated by quantitative polymerase chain reaction for 44 of 46 tested genes. This array study discovered numerous novel mechanosensitive genes, including Lmo4, klk10, and dhh, while confirming well-known ones, such as Klf2, eNOS, and BMP4. Four genes were further validated for protein, including LMO4, which showed higher expression in mouse aortic arch and in human coronary endothelium in an asymmetric pattern. Comparison of in vivo, ex vivo, and in vitro endothelial gene expression profiles indicates that numerous in vivo mechanosensitive genes appear to be lost or dysregulated during culture. Gene ontology analyses show that disturbed flow regulates genes involved in cell proliferation and morphology by 12 hours, followed by inflammatory and immune responses by 48 hours. Determining the functional importance of these novel mechanosensitive genes may provide important insights into understanding vascular biology and atherosclerosis.
Thrombotic thrombocytopenic purpura directly linked with ADAMTS13 inhibition in the baboon (Papio ursinus)
Authors: Feys Hendrik B. , Roodt Jan , Vandeputte Nele , Pareyn Inge , Lamprecht Seb , van Rensburg Walter J. , Anderson Patricia J. , Budde Ulrich , Louw Vernon J. , Badenhorst Philip N. , Deckmyn Hans , Vanhoorelbeke Karen
Published: June 2010

Thrombotic thrombocytopenic purpura (TTP) is the prototypical microangiopathy characterized by disseminated microthromboses, hemolytic anemia, and ultimately organ dysfunction. A link with deficiency of the von Willebrand factor–cleaving protease (ADAMTS13) has been demonstrated, but additional genetic and/or environmental triggers are thought to be required to incite acute illness. Here we report that 4 days of ADAMTS13 functional inhibition is sufficient to induce TTP in the baboon (Papio ursinus), in the absence of inciting triggers because injections with an inhibitory monoclonal antibody (mAb) consistently (n = 6) induced severe thrombocytopenia (< 12 × 109/L), microangiopathic hemolytic anemia, and a rapid rise in serum lactate dehydrogenase. Immunohistochemical staining revealed the characteristic disseminated platelet- and von Willebrand factor–rich thrombi in kidney, heart, brain, and spleen but not lungs. Prolonged inhibition (14 days, n = 1) caused myocardial ischemic damage and asplenia but not death. Control animals (n = 5) receiving equal doses of a noninhibitory anti-ADAMTS13 mAb remained unaffected. Our results provide evidence for a direct link between TTP and ADAMTS13 inhibition and for a mild disease onset. Furthermore, we present a reliable animal model of this disease as an opportunity for the development and validation of novel treatment strategies.
Flavonoids activate pregnane × receptor-mediated CYP3A4 gene expression by inhibiting cyclin-dependent kinases in HepG2 liver carcinoma cells
Authors: Dong Hanqing , Lin Wenwei , Wu Jing , Chen Taosheng
Published: June 2010

Background

The expression of the drug-metabolizing enzyme cytochrome P450 3A4 (CYP3A4) is regulated by the pregnane × receptor (PXR), which is modulated by numerous signaling pathways, including the cyclin-dependent kinase (Cdk) pathway. Flavonoids, commonly consumed by humans as dietary constituents, have been shown to modulate various signaling pathways (e.g., inhibiting Cdks). Flavonoids have also been shown to induce CYPs expression, but the underlying mechanism of action is unknown. Here, we report the mechanism responsible for flavonoid-mediated PXR activation and CYP expression.

Results

In a cell-based screen designed to identify compounds that activate PXR-mediated CYP3A4 gene expression in HepG2 human carcinoma cells, we identified several flavonoids, such as luteolin and apigenin, as PXR activators. The flavonoids did not directly bind to PXR, suggesting that an alternative mechanism may be responsible for flavonoid-mediated PXR activation. Consistent with the Cdk5-inhibitory effect of flavonoids, Cdk5 and p35 (a non-cyclin regulatory subunit required to activate Cdk5) were expressed in HepG2. The activation of Cdk5 attenuated PXR-mediated CYP3A4 expression whereas its downregulation enhanced it. The Cdk5-mediated downregulation of CYP3A4 promoter activity was restored by flavonoids, suggesting that flavonoids activate PXR by inactivating Cdk5. In vitro kinase assays showed that Cdk5 directly phosphorylates PXR. The Cdk kinase profiling assay showed that apigenin inhibits multiple Cdks, suggesting that several Cdks may be involved in activation of PXR by flavonoids.

Conclusions

Our results for the first time link the stimulatory effect of flavonoids on CYP expression to their inhibitory effect on Cdks, through a PXR-mediated mechanism. These results may have important implications on the pharmacokinetics of drugs co-administered with herbal remedy and herbal-drug interactions.
Genomic organization of eukaryotic tRNAs
Authors: Bermudez-Santana Clara , Attolini Camille Stephan-Otto , Kirsten Toralf , Engelhardt Jan , Prohaska Sonja J , Steigele Stephan , Stadler Peter F
Published: June 2010

Background

Surprisingly little is known about the organization and distribution of tRNA genes and tRNA-related sequences on a genome-wide scale. While tRNA gene complements are usually reported in passing as part of genome annotation efforts, and peculiar features such as the tandem arrangements of tRNA gene in Entamoeba histolytica have been described in some detail, systematic comparative studies are rare and mostly restricted to bacteria. We therefore set out to survey the genomic arrangement of tRNA genes and pseudogenes in a wide range of eukaryotes to identify common patterns and taxon-specific peculiarities.

Results

In line with previous reports, we find that tRNA complements evolve rapidly and tRNA gene and pseudogene locations are subject to rapid turnover. At phylum level, the distributions of the number of tRNA genes and pseudogenes numbers are very broad, with standard deviations on the order of the mean. Even among closely related species we observe dramatic changes in local organization. For instance, 65% and 87% of the tRNA genes and pseudogenes are located in genomic clusters in zebrafish and stickleback, resp., while such arrangements are relatively rare in the other three sequenced teleost fish genomes. Among basal metazoa, Trichoplax adhaerens has hardly any duplicated tRNA gene, while the sea anemone Nematostella vectensis boasts more than 17000 tRNA genes and pseudogenes. Dramatic variations are observed even within the eutherian mammals. Higher primates, for instance, have 616 ± 120 tRNA genes and pseudogenes of which 17% to 36% are arranged in clusters, while the genome of the bushbaby Otolemur garnetti has 45225 tRNA genes and pseudogenes of which only 5.6% appear in clusters. In contrast, the distribution is surprisingly uniform across plant genomes. Consistent with this variability, syntenic conservation of tRNA genes and pseudogenes is also poor in general, with turn-over rates comparable to those of unconstrained sequence elements. Despite this large variation in abundance in Eukarya we observe a significant correlation between the number of tRNA genes, tRNA pseudogenes, and genome size.

Conclusions

The genomic organization of tRNA genes and pseudogenes shows complex lineage-specific patterns characterized by an extensive variability that is in striking contrast to the extreme levels of sequence-conservation of the tRNAs themselves. The comprehensive analysis of the genomic organization of tRNA genes and pseudogenes in Eukarya provides a basis for further studies into the interplay of tRNA gene arrangements and genome organization in general.
Response of the mosquito protein interaction network to dengue infection
Authors: Guo Xiang , Xu Yao , Bian Guowu , Pike Andrew D , Xie Yan , Xi Zhiyong
Published: June 2010

Background

Two fifths of the world's population is at risk from dengue. The absence of effective drugs and vaccines leaves vector control as the primary intervention tool. Understanding dengue virus (DENV) host interactions is essential for the development of novel control strategies. The availability of genome sequences for both human and mosquito host greatly facilitates genome-wide studies of DENV-host interactions.

Results

We developed the first draft of the mosquito protein interaction network using a computational approach. The weighted network includes 4,214 Aedes aegypti proteins with 10,209 interactions, among which 3,500 proteins are connected into an interconnected scale-free network. We demonstrated the application of this network for the further annotation of mosquito proteins and dissection of pathway crosstalk. Using three datasets based on physical interaction assays, genome-wide RNA interference (RNAi) screens and microarray assays, we identified 714 putative DENV-associated mosquito proteins. An integrated analysis of these proteins in the network highlighted four regions consisting of highly interconnected proteins with closely related functions in each of replication/transcription/translation (RTT), immunity, transport and metabolism. Putative DENV-associated proteins were further selected for validation by RNAi-mediated gene silencing, and dengue viral titer in mosquito midguts was significantly reduced for five out of ten (50.0%) randomly selected genes.

Conclusions

Our results indicate the presence of common host requirements for DENV in mosquitoes and humans. We discuss the significance of our findings for pharmacological intervention and genetic modification of mosquitoes for blocking dengue transmission.
Detecting separate time scales in genetic expression data
Authors: Orlando David A , Brady Siobhan M , Fink Thomas MA , Benfey Philip N , Ahnert Sebastian E
Published: June 2010

Background

Biological processes occur on a vast range of time scales, and many of them occur concurrently. As a result, system-wide measurements of gene expression have the potential to capture many of these processes simultaneously. The challenge however, is to separate these processes and time scales in the data. In many cases the number of processes and their time scales is unknown. This issue is particularly relevant to developmental biologists, who are interested in processes such as growth, segmentation and differentiation, which can all take place simultaneously, but on different time scales.

Results

We introduce a flexible and statistically rigorous method for detecting different time scales in time-series gene expression data, by identifying expression patterns that are temporally shifted between replicate datasets. We apply our approach to a Saccharomyces cerevisiae cell-cycle dataset and an Arabidopsis thaliana root developmental dataset. In both datasets our method successfully detects processes operating on several different time scales. Furthermore we show that many of these time scales can be associated with particular biological functions.

Conclusions

The spatiotemporal modules identified by our method suggest the presence of multiple biological processes, acting at distinct time scales in both the Arabidopsis root and yeast. Using similar large-scale expression datasets, the identification of biological processes acting at multiple time scales in many organisms is now possible.
YopH inhibits early pro-inflammatory cytokine responses during plague pneumonia
Authors: Cantwell Angelene M , Bubeck Sarah S , Dube Peter H
Published: June 2010

Background

Yersinia pestis is the causative agent of pneumonic plague; recently, we and others reported that during the first 24-36 hours after pulmonary infection with Y. pestis pro-inflammatory cytokine expression is undetectable in lung tissues.

Results

Here, we report that, intranasal infection of mice with CO92 delta yopH mutant results in an early pro-inflammatory response in the lungs characterized by an increase in the pro-inflammatory cytokines Tumor Necrosis Factor-alpha and Interleukin one-beta 24 hours post-infection. CO92 delta yopH colonizes the lung but does not disseminate to the liver or spleen and is cleared from the host within 72 hours post-infection. This is different from what is observed in a wild-type CO92 infection, where pro-inflammatory cytokine expression and immune cell infiltration into the lungs is not detectable until 36-48 h post-infection. CO92 rapidly disseminates to the liver and spleen resulting in high bacterial burdens in these tissues ultimately cumulating in death 72-94 h post-infection. Mice deficient in TNF-alpha are more susceptible to CO92 delta yopH infection with 40% of the mice succumbing to infection.

Conclusions

Altogether, our results suggest that YopH can inhibit an early pro-inflammatory response in the lungs of mice and that this is an important step in the pathogenesis of infection.
Phylogenetic and biogeographic implications inferred by mitochondrial intergenic region analyses and ITS1-5.8S-ITS2 of the entomopathogenic fungi Beauveria bassiana and B. brongniartii
Authors: Ghikas Dimitri V , Kouvelis Vassili N , Typas Milton A
Published: June 2010

Background

The entomopathogenic fungi of the genus Beauveria are cosmopolitan with a variety of different insect hosts. The two most important species, B. bassiana and B. brongniartii, have already been used as biological control agents of pests in agriculture and as models for the study of insect host - pathogen interactions. Mitochondrial (mt) genomes, due to their properties to evolve faster than the nuclear DNA, to contain introns and mobile elements and to exhibit extended polymorphisms, are ideal tools to examine genetic diversity within fungal populations and genetically identify a species or a particular isolate. Moreover, mt intergenic region can provide valuable phylogenetic information to study the biogeography of the fungus.

Results

The complete mt genomes of B. bassiana (32,263 bp) and B. brongniartii (33,920 bp) were fully analysed. Apart from a typical gene content and organization, the Beauveria mt genomes contained several introns and had longer intergenic regions when compared with their close relatives. The phylogenetic diversity of a population of 84 Beauveria strains -mainly B. bassiana (n = 76) - isolated from temperate, sub-tropical and tropical habitats was examined by analyzing the nucleotide sequences of two mt intergenic regions (atp 6-rns and nad 3-atp 9) and the nuclear ITS1-5.8S-ITS2 domain. Mt sequences allowed better differentiation of strains than the ITS region. Based on mt and the concatenated dataset of all genes, the B. bassiana strains were placed into two main clades: (a) the B. bassiana s. l. and (b) the "pseudobassiana". The combination of molecular phylogeny with criteria of geographic and climatic origin showed for the first time in entomopathogenic fungi, that the B. bassiana s. l. can be subdivided into seven clusters with common climate characteristics.

Conclusions

This study indicates that mt genomes and in particular intergenic regions provide molecular phylogeny tools that combined with criteria of geographic and climatic origin can subdivide the B. bassiana s.l. entomopathogenic fungi into seven clusters with common climate characteristics.
Identification of transcription-factor genes expressed in the Arabidopsis female gametophyte
Authors: Wang Dongfang , Zhang Changqing , Hearn David J , Kang Il-Ho , Punwani Jayson A , Skaggs Megan I , Drews Gary N , Schumaker Karen S , Yadegari Ramin
Published: June 2010

Background

In flowering plants, the female gametophyte is typically a seven-celled structure with four cell types: the egg cell, the central cell, the synergid cells, and the antipodal cells. These cells perform essential functions required for double fertilization and early seed development. Differentiation of these distinct cell types likely involves coordinated changes in gene expression regulated by transcription factors. Therefore, understanding female gametophyte cell differentiation and function will require dissection of the gene regulatory networks operating in each of the cell types. These efforts have been hampered because few transcription factor genes expressed in the female gametophyte have been identified. To identify such genes, we undertook a large-scale differential expression screen followed by promoter-fusion analysis to detect transcription-factor genes transcribed in the Arabidopsis female gametophyte.

Results

Using quantitative reverse-transcriptase PCR, we analyzed 1,482 Arabidopsis transcription-factor genes and identified 26 genes exhibiting reduced mRNA levels indeterminate infertile 1mutant ovaries, which lack female gametophytes, relative to ovaries containing female gametophytes. Spatial patterns of gene transcription within the mature female gametophyte were identified for 17 transcription-factor genes using promoter-fusion analysis. Of these, ten genes were predominantly expressed in a single cell type of the female gametophyte including the egg cell, central cell and the antipodal cells whereas the remaining seven genes were expressed in two or more cell types. After fertilization, 12 genes were transcriptionally active in the developing embryo and/or endosperm.

Conclusions

We have shown that our quantitative reverse-transcriptase PCR differential-expression screen is sufficiently sensitive to detect transcription-factor genes transcribed in the female gametophyte. Most of the genes identified in this study have not been reported previously as being expressed in the female gametophyte. Therefore, they might represent novel regulators and provide entry points for reverse genetic and molecular approaches to uncover the gene regulatory networks underlying female gametophyte development.
Chromosomal loci important for cotyledon opening under UV-B in Arabidopsis thaliana
Authors: Conte Mariana , de Simone Silvia , Simmons Susan J , Ballaré Carlos L , Stapleton Ann E
Published: June 2010

Background

Understanding of the genetic architecture of plant UV-B responses allows extensive targeted testing of candidate genes or regions, along with combinations of those genes, for placement in metabolic or signal transduction pathways.

Results

Composite interval mapping and single-marker analysis methods were used to identify significant loci for cotyledon opening under UV-B in four sets of recombinant inbred lines. In addition, loci important for canalization (stability) of cotyledon opening were detected in two mapping populations. One candidate locus contained the gene HY5. Mutant analysis demonstrated that HY5 was required for UV-B-specific cotyledon opening.

Conclusions

Structured mapping populations provide key information on the degree of complexity in the genetic control of UV-B-induced cotyledon opening in Arabidopsis. The loci identified using quantitative trait analysis methods are useful for follow-up testing of candidate genes.
The experience of college students with pulmonary tuberculosis in Shaanxi, China: a qualitative study
Authors: Zhang Shao-Ru , Yan Hong , Zhang Jin-Jing , Zhang Tian-Hua , Li Xiao-Hong , Zhang Yin-Ping
Published: June 2010

Background

The prevalence of pulmonary tuberculosis among college students in Shaanxi is high. Although tuberculosis leaves much psychological and social impact on patients, little is known about its impact on college students. The objective of this study is to explore the experiences and psychological process of college students with pulmonary tuberculosis in Shaanxi, China.

Methods

17 college students with pulmonary tuberculosis were recruited purposively from 9 colleges in Shaanxi. In-depth interviews were conducted to collect data and a thematic framework analysis was used.

Results

The participants reported that pulmonary tuberculosis deeply influenced their mental health. They were fearful to the nature of pulmonary tuberculosis at the stage of diagnosis, anxious about the illness before the period of diagnosis and the early week of the treatment, excessive worry immediately before the first recheck. They expected an early full recovery, bored on tedious treatment life and worried about future heath and prospects during the whole treatment phase. Their daily life was also influenced, namely discontinued studies, isolation and increased financial burden. They also reported that they could get strong supports from family members, while little supports from healthcare workers and their friends.

Conclusions

The participants' psychological pressure was significant during the treatment. In addition, there was serious conflict between treatment and study; social support provided for them was insufficient. Healthcare workers should provide psychological support for college students with pulmonary tuberculosis according to the psychological characteristics and offer social support through strengthening communication with them. Colleges should follow governmental policies on TB exactly and provide opportunities for the patients to continue their studies.
Secretion of extracellular hsp90α via exosomes increases cancer cell motility: a role for plasminogen activation
Authors: McCready Jessica , Sims Jessica D , Chan Doug , Jay Daniel G
Published: June 2010

Background

Metastasis is a multi-step process that is responsible for the majority of deaths in cancer patients. Current treatments are not effective in targeting metastasis. The molecular chaperone hsp90α is secreted from invasive cancer cells and activates MMP-2 to enhance invasiveness, required for the first step in metastasis.

Methods

We analyzed the morphology and motility of invasive cancer cells that were treated with exogenous exosomes in the presence or absence of hsp90α. We performed mass spectrometry and immunoprecipitation to identify plasminogen as a potential client protein of extracellular hsp90α. Plasmin activation assays and migration assays were performed to test if plasminogen is activated by extracellular hsp90α and has a role in migration.

Results

We found that hsp90α is secreted in exosomes in invasive cancer cells and it contributes to their invasive nature. We identified a novel interaction between hsp90α and tissue plasminogen activator that together with annexin II, also found in exosomes, activates plasmin. Extracellular hsp90α promotes plasmin activation as well as increases plasmin dependent cell motility.

Conclusions

Our data indicate that hsp90α is released by invasive cancer cells via exosomes and implicates hsp90α in activating plasmin, a second protease that acts in cancer cell invasion.
The prevalence and social patterning of chronic diseases among older people in a population undergoing health transition. A 10/66 Group cross-sectional population-based survey in the Dominican Republic
Authors: Acosta Daisy , Rottbeck Ruth , Rodríguez Juana G , González Loida M , Almánzar Mary R , Minaya Susana N , Ortiz Maria del C , Ferri Cleusa P , Prince Martin J
Published: June 2010

Background

Very little of the increased attention towards chronic diseases in countries with low and middle incomes has been directed towards older people, who contribute 72% of all deaths, and 14% of all Disability Adjusted Life Years linked to this group of conditions in those regions. We aimed to study the prevalence of physical, mental and cognitive diseases and impairments among older people in the Dominican Republic, their social patterning, and their relative contributions to disability.

Methods

A cross-sectional catchment area one-phase survey of chronic disease diagnoses, physical impairments, risk factors and associated disability among 2011 people aged 65 years and over (of whom 1451 gave fasting blood samples) in Santo Domingo, Dominican Republic.

Results

The most prevalent diagnoses were hypertension (73.0%), anaemia (35.0%), diabetes (17.5%), depression (13.8%) and dementia (11.7%), with 39.6% meeting criteria for metabolic syndrome. After direct standardization (for age and sex) the prevalences of stroke (standardized morbidity ratio [SMR] 100) and hypertension (SMR 108) were similar to those in the United States of America National Health and Nutrition Examination Survey (NHANES reference SMR 100), while those of diabetes (SMR 83) and metabolic syndrome (SMR 72) were somewhat lower. Anaemia was three times more common than in the USA (SMR 310). Diabetes, hypertension, dyslipidaemia, obesity and the metabolic syndrome were associated with affluence and female sex. Arthritis, anaemia, dementia and stroke were strongly age-associated and these conditions were also the main independent contributors to disability.

Conclusions

The prevalence of many chronic diseases is similar in predominately low socioeconomic status neighbourhoods in the Dominican Republic to that in the USA. Prevalence of age-associated conditions is likely to increase with demographic ageing. There is also scope for increases in cardiovascular disease prevalence, if, as observed in other settings undergoing the epidemiologic transition, the burden of risk factors shifts towards the less affluent. Monitoring future trends in the prevalence and social patterning of chronic diseases may help to assess the effectiveness and equity of primary and secondary prevention strategies. Specific recommendations from our research include identifying and targeting the causes of anaemia among older people, and addressing women's health disadvantages.
Fibrin clot structure remains unaffected in young, healthy individuals after transient exposure to diesel exhaust
Authors: Metassan Sofian , Routledge Michael N , Lucking Andrew J , de Willige Shirley Uitte , Philippou Helen , Mills Nicholas L , Newby David E , Ariëns Robert AS
Published: June 2010

Exposure to urban particulate matter has been associated with an increased risk of cardiovascular disease and thrombosis. We studied the effects of transient exposure to diesel particles on fibrin clot structure of 16 healthy individuals (age 21- 44). The subjects were randomly exposed to diesel exhaust and filtered air on two separate occasions. Blood samples were collected before exposure, and 2 and 6 hours after exposure. There were no significant changes on clot permeability, maximum turbidity, lag time, fibre diameter, fibre density and fibrinogen level between samples taken after diesel exhaust exposure and samples taken after filtered air exposure. These data show that there are no prothrombotic changes in fibrin clot structure in young, healthy individuals exposed to diesel exhaust.
P3MC: A double blind parallel group randomised placebo controlled trial of Propranolol and Pizotifen in preventing migraine in children
Authors: Silcocks Paul , Whitham Diane , Whitehouse William Patrick
Published: June 2010

Background

A recent Cochrane Review demonstrated the remarkable lack of reliable clinical trials of migraine treatments for children, especially for the two most prescribed preventative treatments in the UK, Propranolol and Pizotifen.

Migraine trials in both children and adults have high placebo responder rates, e.g. of 23%, but for a trial's results to be generalisable "placebo responders" should not be excluded and for a drug to be worthwhile it should be clearly superior, both clinically and statistically, to placebo.

Methods/Design

Two multicentre, two arm double blind parallel group randomised controlled trials, with allocation ratio of 2:1 for each comparison, Propranolol versus placebo and Pizotifen versus placebo. The trial is designed to test whether Propranolol is superior to placebo and whether Pizotifen is superior to placebo for the prevention of migraine attacks in children aged 5 - 16 years referred to secondary care out-patient settings with frequent migraine (2-6/4 weeks). The primary outcome measure is the number of migraine attacks during trial weeks 11 to 14.

Discussion

A strength of this trial is the participation of clinically well defined migraine patients who will also be approached to help with future longer-term follow-up studies.

Trial Registration

ISRCTN97360154
Early clinical experience of radiotherapy of prostate cancer with volumetric modulated arc therapy
Authors: Pesce Gianfranco A , Clivio Alessandro , Cozzi Luca , Nicolini Giorgia , Richetti Antonella , Salati Emanuela , Valli Mariacarla , Vanetti Eugenio , Fogliata Antonella
Published: June 2010

Background

To report about initial clinical experience in radiation treatment of carcinoma of prostate with volumetric modulated arcs with the RapidArc (RA) technology.

Methods

Forty-five patients with a median age of 72 ± 3, affected by prostate carcinoma (T1c: 22 patients, T2a-b: 17 patients, T3a-b: 6 patients. N0: 43 patients, N1-Nx: 2 patients, all M0), with initial PSA of 10.0 ± 3.0 ng/mL, were treated with RapidArc in a feasibility study. All patients were treated with single arc using 6MV photons. Dose prescription ranged between 76 (7 patients) and 78 Gy (38 patients) in 2Gy/fraction. Plan quality was assessed by means of Dose Volume Histogram (DVH) analysis. Technical parameters of arcs and pre-treatment quality assurance results (Gamma Agreement Index, GAI) are reported to describe delivery features. Early toxicity was scored (according to the Common Terminology Criteria of Adverse Effects scale, CTCAE, scale) at the end of treatment together with biochemical outcome (PSA).

Results

From DVH data, target coverage was fulfilling planning objectives: V95% was in average higher than 98% and V107%~0.0% (D2%~104.0% in average). Homogeneity D5%-D95% ranged between 6.2 ± 1.0% to 6.7 ± 1.3%. For rectum, all planning objectives were largely met (e.g. V70Gy = 10.7 ± 5.5% against an objective of < 25%) similarly for bladder (e.g. D2% = 79.4 ± 1.2Gy against an objective of 80.0Gy). Maximum dose to femurs was D2% = 36.7 ± 5.4Gy against an objective of 47Gy. Monitor Units resulted: MU/Gy = 239 ± 37. Average beam on time was 1.24 ± 0.0 minutes. Pre-treatment GAI resulted in 98.1 ± 1.1%. Clinical data were recorded as PSA at 6 weeks after RT, with median values of 0.4 ± 0.4 ng/mL. Concerning acute toxicity, no patient showed grade 2-3 rectal toxicity; 5/42 (12%) patients experienced grade 2 dysuria; 18/41 (44%) patients preserved complete or partial erectile function.

Conclusion

RapidArc proved to be a safe, qualitative and advantageous treatment modality for prostate cancer.
Hematopoietic differentiation: a coordinated dynamical process towards attractor stable states
Authors: Felli Nadia , Cianetti Luciano , Pelosi Elvira , Carè Alessandra , Liu Chang Gong , Calin George A , Rossi Simona , Peschle Cesare , Marziali Giovanna , Giuliani Alessandro
Published: June 2010

Background

The differentiation process, proceeding from stem cells towards the different committed cell types, can be considered as a trajectory towards an attractor of a dynamical process. This view, taking into consideration the transcriptome and miRNome dynamics considered as a whole, instead of looking at few 'master genes' driving the system, offers a novel perspective on this phenomenon. We investigated the 'differentiation trajectories' of the hematopoietic system considering a genome-wide scenario.

Results

We developed serum-free liquid suspension unilineage cultures of cord blood (CB) CD34+ hematopoietic progenitor cells through erythroid (E), megakaryocytic (MK), granulocytic (G) and monocytic (Mo) pathways. These cultures recapitulate physiological hematopoiesis, allowing the analysis of almost pure unilineage precursors starting from initial differentiation of HPCs until terminal maturation. By analyzing the expression profile of protein coding genes and microRNAs in unilineage CB E, MK, G and Mo cultures, at sequential stages of differentiation and maturation, we observed a coordinated, fully interconnected and scalable character of cell population behaviour in both transcriptome and miRNome spaces reminiscent of an attractor-like dynamics. MiRNome and transcriptome space differed for a still not terminally committed behaviour of microRNAs.

Conclusions

Consistent with their roles, the transcriptome system can be considered as the state space of a cell population, while the continuously evolving miRNA space corresponds to the tuning system necessary to reach the attractor. The behaviour of miRNA machinery could be of great relevance not only for the promise of reversing the differentiated state but even for tumor biology.
Massive variceal bleeding secondary to splenic vein thrombosis successfully treated with splenic artery embolization: a case report
Authors: Paramythiotis Daniel , Papavramidis Theodossis S , Giavroglou Konstantinos , Potsi Stamatia , Girtovitis Fotis , Michalopoulos Antonis , Papadopoulos Vassilis N , Prousalidis John
Published: June 2010

Introduction

Splenic vein thrombosis results in localized portal hypertension called sinistral portal hypertension, which may also lead to massive upper gastrointestinal bleeding. Symptomatic sinistral portal hypertension is usually best treated by splenectomy, but interventional radiological techniques are safe and effective alternatives in the management of a massive hemorrhage, particularly in cases that have a high surgical risk.

Case presentation

We describe a 23-year-old Greek man with acute massive gastric variceal bleeding caused by splenic vein thrombosis due to a missing von Leiden factor, which was successfully managed with splenic arterial embolization.

Conclusions

Interventional radiological techniques are attractive alternatives for patients with a high surgical risk or in cases when the immediate surgical excision of the spleen is technically difficult. Additionally, surgery is not always successful because of the presence of numerous portal collaterals and adhesion. Splenic artery embolization is now emerging as a safe and effective alternative to surgery in the management of massive hemorrhage from gastric varices due to splenic vein thrombosis, which often occurs in patients with hypercoagulability.
Pleural aspergillosis complicated by recurrent pneumothorax: a case report
Authors: Zhang Weihua , Hu Ye , Chen Liang'an , Gao Jie , Xie Lixin
Published: June 2010

Introduction

Pneumothorax as the first symptom of pleural aspergillosis is rare.

Case presentation

A 31-year-old asthmatic Chinese man presented with recurrent spontaneous pneumothorax and underwent lobectomy due to persistent air leakage. Aspergillus was detected histopathologically in the visceral pleural cavity. He was treated with itraconazole at 200 mg a day, and nine months later he had no recurrent pneumothorax or aspergillus infection.

Conclusion

Recurrent pneumothorax may be a rare manifestation of aspergillus infection. Aspergillus species infection should be considered in the differential diagnosis of recurrent pneumothorax patients, particularly those with chronic lung disease.
Relationship and prognostic significance of SPARC and VEGF protein expression in colon cancer
Authors: Liang Jian-fang , Wang Hong-kun , Xiao Hong , Li Ning , Cheng Cai-xia , Zhao Yu-ze , Ma Yan-bo , Gao Jian-zhong , Bai Rui-bing , Zheng Hui-xia
Published: June 2010

Background

SPARC (secreted protein, acidic and rich in cysteine) is closely related with the progress, invasion and metastasis of malignant tumor and angiogenesis.

Methods

Using human colon adenocarcinoma tissues (hereinafter referred to as colon cancer) and their corresponding non-diseased colon from 114 patients' biopsies, the expression of SPARC and vascular endothelial growth factor (VEGF) were investigated by immunohistochemistry staining to assessment the relationship between SPARC and VEGF, as well as their prognostic significance in patients. Evaluation of VEGF expression level with the same tissues was used to establish the antigenic profiles, and the marker of CD34 staining was used as an indicator of microvessel density (MVD).

Results

SPARC expression was mainly in the stromal cells surrounding the colon cancer, and was significant difference in those tissues with the lymph node metastasis and differentiation degree of tumor. Expression of SPARC was significantly correlated with the expression of VEGF and MVD in colon cancer tissues. Patients with low or absence expressing SPARC had significantly worse overall survival and disease-free survival in a Single Factor Analysis; Cox Regression Analysis, SPARC emerged as an overall survival and disease-free survival independent prognostic factor for colon cancer.

Conclusion

The low expression or absence of stromal SPARC was an independent prognostic factor for poor prognosis of colon cancer. SPARC maybe involved in the regulation of anti-angiogenesis by which it may serve as a novel target for colon cancer treatment as well as a novel distinctive marker.
Effectiveness and safety of adalimumab in patients with ankylosing spondylitis or psoriatic arthritis and history of anti-tumor necrosis factor therapy
Authors: Rudwaleit Martin , Van den Bosch Filip , Kron Martina , Kary Sonja , Kupper Hartmut
Published: June 2010

Introduction

Tumor necrosis factor (TNF) antagonists reduce the signs and symptoms of spondyloarthritides, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Our objective was to evaluate the effectiveness and safety of adalimumab, 40 mg every other week, for patients with AS or PsA and prior treatment with infliximab (IFX) and/or etanercept (ETN).

Methods

Both trials were 12-week, open-label studies with an optional extension period up to week 20. Patients were stratified by history of anti-TNF treatment, prior anti-TNF therapy received (IFX, ETN, or both), and reason for discontinuation of prior TNF antagonist. ETN was discontinued ≥ 3 weeks, and IFX was discontinued ≥ 2 months before the first adalimumab administration. Effectiveness at week 12 was evaluated by using observed standard-outcome measurements for AS and PsA.

Results

At week 12 of adalimumab treatment, Bath Ankylosing Spondylitis Disease Activity Index 50 responses were achieved by 40.8% of 326 patients with AS who had received prior anti-TNF therapy and by 63.0% of 924 patients with AS who were naive to TNF antagonist. Observed response rates were generally greater for patients who discontinued the prior anti-TNF therapy because of loss of response or intolerance than for patients who discontinued because of lack of response. Median changes in swollen-joint count and in enthesitis score were similar in patients with and without prior TNF-antagonist treatment. Modified PsA response criteria were fulfilled by 71.2% of 66 patients with PsA, with prior exposure to TNF antagonists, and by 78.8% of 376 patients with no history of anti-TNF therapy. The percentages of patients with PsA attaining a Physician's Global Assessment of psoriasis of "Clear/Almost clear" increased from 33.3% to 61.0% for patients with prior IFX and/or ETN treatment and from 34.6% to 69.7% for patients without anti-TNF therapy. The median change in the Nail Psoriasis Severity Index was -6 for both groups. In both studies, patterns of adverse events were similar for patients with and without prior anti-TNF therapy and were consistent with the known safety profile of adalimumab.

Conclusions

Patients with AS or PsA previously treated with IFX and/or ETN experienced clinically relevant improvements of their diseases after 12 weeks of adalimumab.

Trial registrations

ClinicalTrials.gov NCT00478660 and NCT00235885.