bluuebunny/crossref_metadata_2025 huggingface dataset:
Commentary: How can Creativity in a Social Context be Possible?
Authors: Min Han
Published: May 2010

Glăveanu’s (2010) ‘We-paradigm’ creativity is related to culture and social context, especially due to his emphasis on the role of the community as a provider of criteria for evaluating creativity. In addition, he suggests five principles for studying this kind of creativity. In this article, I will apply these principles to study the Korean cultural phenomenon , Shinmyeong. The characteristics of Shinmyeong, its expressive process and the co-experience, are introduced from the perspective of creativity. By taking musical performances as an example, the expressive process in Shinmyeong experience is considered as the process that may generate creative activities. The interpersonal aspects of the expressive process are discussed within the framework Glăveanu suggests.
An Evidence-Based Practice Model Across the Academic and Clinical Settings
Authors: Wolter Julie A. , Corbin-Lewis Kim , Self Trisha , Elsweiler Anne
Published: May 2010

This tutorial is designed to provide academic communication sciences and disorders (CSD) programs, at both the undergraduate and graduate levels, with a comprehensive instructional model on evidence-based practice (EBP). The model was designed to help students view EBP as an ongoing process needed in all clinical decision making. The three facets of EBP (research, client/contextual factors, and clinical expertise) are addressed through explicit teaching practices and assignments in didactic coursework and considered in parallel with a concurrent clinical practicum. At the graduate level, the reciprocal nature between theory, research, and practice is emphasized using components such as structured EBP protocols in coursework and clinic, application of clinical case studies that emphasize EBP procedures, and the integration of authentic research assignments. Examples are provided, and ways in which academic faculty and clinical educators can actively engage in creating a shared language and culture at all levels in a CSD program are presented.
Fledgling Psychopathy in the Classroom: ADHD Subtypes, Psychopathy, and Reading Comprehension in a Community Sample of Adolescents
Authors: DeLisi Matt , Vaughn Michael , Beaver Kevin M. , Wexler Jade , Barth Amy E. , Fletcher Jack M.
Published: May 2010

The current study explores characteristics that are associated with fledgling psychopathy and educational outcomes relating to reading comprehension performance in a community sample of 432 middle school students. Latent class analysis (LCA) produced a four-class solution. Class 1 was a large (71.5% of sample) ‘‘control’’ group of youths with no attention/hyperactivity deficits and the highest reading comprehension scores. Class 2 was 11.6% of the sample and was consistent with traits associated with attention deficit hyperactivity disorder (ADHD) predominantly inattentive type. Class 3 was 7.4% of the sample and was consistent with traits associated with ADHD predominantly hyperactive—impulsive type. Class 4 was 9.5% of the sample and was consistent with traits associated with ADHD combined type. Classes 2 and 4 were characterized by elevated levels of psychopathic and callous-unemotional (CU) traits and lower educational performance. This study extends the utility of fledgling psychopathy to educational outcomes, which has broad implications for adolescent development, delinquency, and youth violence.
Trinity Evolution
Authors: Rush Shannon M.
Published: May 2010

Biologic augmentation of orthopaedic procedures is a time-tested useful adjunct. The ability to predictably heal all fractures and arthrodesis procedures is still elusive because of multiple factors. The next frontier in musculoskeletal medicine and surgery will involve increasing biologic manipulation of the healing environment. Mesenchymal stem cell allograft is viable living biologic material that is capable of new bone formation and osteointegration at the implantation site.
Chronic obstructive pulmonary disease: an update of treatment related to frequently associated comorbidities
Authors: Sinden Nicola J. , Stockley Robert A.
Published: May 2010

Chronic obstructive pulmonary disease (COPD) is associated with a pulmonary inflammatory response to inhaled substances, and individuals with COPD often have raised levels of several circulating inflammatory markers indicating the presence of systemic inflammation. Recently, there has been increasing interest in comorbidities associated with COPD such as skeletal muscle dysfunction, cardiovascular disease, osteoporosis, diabetes and lung cancer. These conditions are associated with a similar inflammation-based pathophysiology to COPD, and may represent a lung inflammatory ‘overspill’ to distant organs. Cardiovascular disease is a significant cause of mortality in COPD, and the concepts of an inflammatory link raise the possibility that treatment for one organ may show benefits to comorbidities in other organs. When considering treatment of COPD and its comorbidities, one approach is to target the pulmonary inflammation and hence reduce any ‘overspill’ effect of inflammatory mediators systemically as suggested by response to inhaled corticosteroids. Alternatively, treatment targeted towards comorbid organs may alter features of pulmonary disease as statins, angiotensin-converting enzyme (ACE) inhibitors and peroxisome proliferator-activated receptor (PPAR) agonists may have beneficial effects on COPD by reducing exacerbations and mortality. Newer anti-inflammatory treatments, such as phosphodiesterase 4 (PDE4), nuclear factor(NF)-kB, and p38 mitogen-activated protein kinase (MAPK) inhibitors, are given systemically and may confer benefits to both COPD and its comorbidities. With common inflammatory pathways it might be expected that successful anti-inflammatory therapy in one organ may also influence others. In this review we explore the concepts of systemic inflammation in COPD and current evidence for treatment of its related comorbidities.
CD62L expression identifies a unique subset of polyfunctional CD56dim NK cells
Authors: Juelke Kerstin , Killig Monica , Luetke-Eversloh Merlin , Parente Eliana , Gruen Joachim , Morandi Barbara , Ferlazzo Guido , Thiel Andreas , Schmitt-Knosalla Isabela , Romagnani Chiara
Published: May 2010

Human natural killer (NK) cells comprise 2 main subsets, CD56bright and CD56dim cells, that differ in function, phenotype, and tissue localization. To further dissect the heterogeneity of CD56dim cells, we have performed transcriptome analysis and functional ex vivo characterization of human NK-cell subsets according to the expression of markers related to differentiation, migration or competence. Here, we show for the first time that the ability to respond to cytokines or to activating receptors is mutually exclusive in almost all NK cells with the exception of CD56dim CD62L+ cells. Indeed, only these cells combine the ability to produce interferon-γ after cytokines and proliferate in vivo during viral infection with the capacity to kill and produce cytokines upon engagement of activating receptors. Therefore, CD56dim CD62L+ cells represent a unique subset of polyfunctional NK cells. Ex vivo analysis of their function, phenotype, telomere length, frequencies during ageing as well as transfer experiments of NK-cell subsets into immunodeficient mice suggest that CD56dim CD62L+ cells represent an intermediate stage of NK-cell maturation, which after restimulation can accomplish multiple tasks and further develop into terminally differentiated effectors.
Erythropoietin: back to basics
Authors: Jelkmann Wolfgang
Published: May 2010

In this issue of Blood, Sinclair and colleagues1 and Swift and colleagues2 report that the Epo receptor is barely detectable in nonhematopoietic tissues, casting doubt on the role of Epo as a pleiotropic hormone. The results not only have relevance for off-label clinical trials using recombinant human Epo for tissue-protection, but have important implications regarding Epo's alleged effects on tumor cells.
Identification of archaeal proteins that affect the exosome function in vitro
Authors: Luz Juliana S , Ramos Celso RR , Santos Márcia CT , Coltri Patricia P , Palhano Fernando L , Foguel Debora , Zanchin Nilson IT , Oliveira Carla C
Published: May 2010

Background

The archaeal exosome is formed by a hexameric RNase PH ring and three RNA binding subunits and has been shown to bind and degrade RNA in vitro. Despite extensive studies on the eukaryotic exosome and on the proteins interacting with this complex, little information is yet available on the identification and function of archaeal exosome regulatory factors.

Results

Here, we show that the proteins PaSBDS and PaNip7, which bind preferentially to poly-A and AU-rich RNAs, respectively, affect the Pyrococcus abyssi exosome activity in vitro. PaSBDS inhibits slightly degradation of a poly-rA substrate, while PaNip7 strongly inhibits the degradation of poly-A and poly-AU by the exosome. The exosome inhibition by PaNip7 appears to depend at least partially on its interaction with RNA, since mutants of PaNip7 that no longer bind RNA, inhibit the exosome less strongly. We also show that FITC-labeled PaNip7 associates with the exosome in the absence of substrate RNA.

Conclusions

Given the high structural homology between the archaeal and eukaryotic proteins, the effect of archaeal Nip7 and SBDS on the exosome provides a model for an evolutionarily conserved exosome control mechanism.
Preferred analysis methods for Affymetrix GeneChips. II. An expanded, balanced, wholly-defined spike-in dataset
Authors: Zhu Qianqian , Miecznikowski Jeffrey C , Halfon Marc S
Published: May 2010

Background

Concomitant with the rise in the popularity of DNA microarrays has been a surge of proposed methods for the analysis of microarray data. Fully controlled "spike-in" datasets are an invaluable but rare tool for assessing the performance of various methods.

Results

We generated a new wholly defined Affymetrix spike-in dataset consisting of 18 microarrays. Over 5700 RNAs are spiked in at relative concentrations ranging from 1- to 4-fold, and the arrays from each condition are balanced with respect to both total RNA amount and degree of positive versus negative fold change. We use this new "Platinum Spike" dataset to evaluate microarray analysis routes and contrast the results to those achieved using our earlier Golden Spike dataset.

Conclusions

We present updated best-route methods for Affymetrix GeneChip analysis and demonstrate that the degree of "imbalance" in gene expression has a significant effect on the performance of these methods.
Conditional expression of Spry1 in neural crest causes craniofacial and cardiac defects
Authors: Yang Xuehui , Kilgallen Sean , Andreeva Viktoria , Spicer Douglas B , Pinz Ilka , Friesel Robert
Published: May 2010

Background

Growth factors and their receptors are mediators of organogenesis and must be tightly regulated in a temporal and spatial manner for proper tissue morphogenesis. Intracellular regulators of growth factor signaling pathways provide an additional level of control. Members of the Sprouty family negatively regulate receptor tyrosine kinase pathways in several developmental contexts. To gain insight into the role of Spry1 in neural crest development, we analyzed the developmental effects of conditional expression of Spry1 in neural crest-derived tissues.

Results

Here we report that conditional expression of Spry1 in neural crest cells causes defects in craniofacial and cardiac development in mice. Spry1;Wnt1-Cre embryos die perinatally and exhibit facial clefting, cleft palate, cardiac and cranial nerve defects. These defects appear to be the result of decreased proliferation and increased apoptosis of neural crest and neural crest-derived cell populations. In addition, the domains of expression of several key transcription factors important to normal craniofacial and cardiac development including AP2, Msx2, Dlx5, and Dlx6 were reduced in Spry1;Wnt1-Cre transgenic embryos.

Conclusion

Collectively, these data suggest that Spry1 is an important regulator of craniofacial and cardiac morphogenesis and perturbations in Spry1 levels may contribute to congenital disorders involving tissues of neural crest origin.
Definition of novel cell envelope associated proteins in Triton X-114 extracts of Mycobacterium tuberculosis H37Rv
Authors: Målen Hiwa , Pathak Sharad , Søfteland Tina , de Souza Gustavo A , Wiker Harald G
Published: May 2010

Background

Membrane- and membrane-associated proteins are important for the pathogenicity of bacteria. We have analysed the content of these proteins in virulentMycobacterium tuberculosisH37Rv using Triton X-114 detergent-phase separation for extraction of lipophilic proteins, followed by their identification with high resolution mass spectrometry.

Results

In total, 1417 different proteins were identified.In silicoanalysis of the identified proteins revealed that 248 proteins had at least one predicted trans-membrane region. Also, 64 of the identified proteins were predicted lipoproteins, and 54 proteins were predicted as outer membrane proteins. Three-hundred-and-ninety-five of the observed proteins, including 91 integral membrane proteins were described for the first time. Comparison of abundance levels of the identified proteins was performed using the exponentially modified protein abundance index (emPAI) which takes into account the number of the observable peptides to the number of experimentally observed peptide ions for a given protein. The outcome showed that among the membrane-and membrane-associated proteins several proteins are present with high relative abundance. Further, a close examination of the lipoprotein LpqG (Rv3623) which is only detected in the membrane fractions ofM. tuberculosisbut not inM. bovis, revealed that the homologous gene inM. bovislack the signal peptide and lipobox motif, suggesting impaired export to the membrane.

Conclusions

Altogether, we have identified a substantial proportion of membrane- and membrane-associated proteins ofM. tuberculosisH37Rv, compared the relative abundance of the identified proteins and also revealed subtle differences between the different members of theM. tuberculosiscomplex.
Assessment of insulin resistance by a 13C glucose breath test: a new tool for early diagnosis and follow-up of high-risk patients
Authors: Mizrahi Meir , Lalazar Gadi , Adar Tomer , Raz Itamar , Ilan Yaron
Published: May 2010

Background/Aims

Insulin resistance (IR) plays an important role in the pathogenesis of diabetes and non-alcoholic fatty liver disease (NAFLD). Current methods for insulin resistance detection are cumbersome, or not sensitive enough for early detection and follow-up. The BreathID® system can continuously analyse breath samples in real-time at the point-of-care. Here we determined the efficacy of the BreathID® using the 13C-Glucose breath test (GBT) for evaluation of insulin resistance.

Methods

Twenty healthy volunteers were orally administered 75 mg of 13C-glucose 1-13C. An oral glucose tolerance test (OGTT) was performed immediately; followed by serum glucose and insulin level determinations using GBT. GBT and OGTT were repeated following exercise, which alters insulin resistance levels.

Results

Within-subject correlations of GBT parameters with serum glucose and serum insulin levels were high. Before and after exercise, between-subjects correlations were high between the relative insulin levels and the % dose recoveries at 90 min (PDR 90), and the cumulative PDRs at 60 min (CPDR 60). Pairwise correlations were identified between pre-exercise Homeostasis Model Assessment (HOMA) IR at 90 min and PDR 90; HOMA B (for beta cell function) 120 and CPDR 30; HOMA IR 60 and peak time post-exercise; and HOMA B 150 with PDR 150.

Conclusions

The non-invasive real-time BreathID® GBT reliably assesses changes in liver glucose metabolism, and the degree of insulin resistance. It may serve as a non-invasive tool for early diagnosis and follow up of patients in high-risk groups.
A case of gangliocytic paraganglioma in the ampulla of Vater
Authors: Kwon Junsik , Lee Seung Eun , Kang Mee Joo , Jang Jin-Young , Kim Sun-Whe
Published: May 2010

Background

Duodenal gangliocytic paraganglioma is an extremely rare tumor and few cases have been reported to date.

Case presentation

The authors report a case of gangliocytic paraganglioma verified by post-op pathology after pancreaticoduodenectomy for a tumor in the ampulla of Vater. The 56-year-old male patient concerned visited our emergency room with melena that started one week prior to hospitalization. The patient was diagnosed to have a tumor in the ampulla of Vater with bleeding on its surface. However post-op, he was diagnosed as having gangliocytic paraganglioma by immunohistochemistry.

Conclusion

This tumor has precise clinical implications, and if continuous follow up is conducted after careful diagnosis and surgical treatment, invasive major operations, such as, radical pancreaticoduodenectomy can be avoided.
Skin Test Reactivity to Indoor Allergens Correlates with Asthma Severity in Jeddah, Saudi Arabia
Authors: Koshak Emad A
Published: May 2010

Background

There is increased emphasis on the role of indoor allergens in asthma.

Objective

To examine the spectrum of skin test reactivity (sensitization) to indoor allergens and its correlation with asthma severity in Jeddah, Saudi Arabia.

Methods

Asthmatic patients referred to the allergy clinic at King Abdulaziz University Hospital (KAUH) in Jeddah were studied. Measures of clinical severity were adopted from national and international asthma guidelines. The degree of sensitization was assessed by the wheal size (positive ≥ 3 mm) from standard skin-prick tests for the following common indoor inhalant allergens: house dust mites (Dermatophagoides pteronyssinus [Dp] and Dermatophagoides farinae [Df]), cat, and cockroach.

Results

Skin test results from 113 of 151 (74.8%) asthmatic patients were positive for one or more allergens. The patients' ages ranged between 9 and 63 years (mean, 30 ± 13 years), and females constituted 65.5%. The predominant asthma severity level was moderate persistent (55.8%), followed by mild persistent (33.6%). The prevalences of sensitization to indoor allergens were as follows: Dp, 87% (3-25 mm [mean, 7 mm]); Df, 84% (3-20 mm [mean, 7 mm]); cat, 44% (3-15 mm [mean, 6 mm]); and cockroach, 33% (3-12 mm [mean, 4 mm]). Higher asthma severity levels were significantly correlated with the number of allergens with positive sensitization (R = 0.3, p < .001) and with the degree of sensitization to house dust mites (Dp [degrees of freedom {df} = 16, p < .001] and Df [df = 17, p < .01]) but not to cat (df = 10, p < .24) or cockroach (df = 8, p < .36).

Conclusions

Immunoglobulin E-mediated skin test reactivity to indoor allergens, particularly to house dust mites, was common in asthmatic patients from Jeddah at KAUH. Increased sensitization was associated with higher levels of asthma severity, which is compatible with the literature. This emphasizes the importance of identifying sensitization to relevant indoor allergens in the clinical evaluation of asthmatic persons.
Erythropoietic Protoporphyria Masquerading as Angioedema in a 4-Year-Old Female
Authors: Wang Helen C , Yousef Ejaz
Published: May 2010

Angioedema is a common presentation with a broad differential, including rare disorders with which an allergist must be familiar. Our objective was to report a case of swelling of the hands and feet mimicking angioedema with hepatomegaly in a 4-year-old girl. The patient was evaluated for painful swelling of the hands and feet after exposure to sun. Examination revealed edema and erythema of the extremities and hepatomegaly. Laboratory evaluation included elevated liver transaminases and plasma protoporphyrin, with normal urine porphyrins. Liver biopsy confirmed the diagnosis of erythropoietic protoporphyria, a disorder of heme biosynthesis in which patients may present with photosensitivity and angioedema. It is important for allergists to recognize this entity in patients with cutaneous disorders of unclear etiology in order to prevent possible life-threatening sequelae.
Prevalence and Severity of Asthma, Rhinitis, and Atopic Eczema in 13- to 14-Year-Old Schoolchildren from Southern Brazil
Authors: Neto Arnaldo C Porto , Annes Rafael D'Agostini , Wolff Nathalia MM , Klein Andréia P , dos Santos Francisco C , Dullius Juliana L , Gressler Marina , Muller Letícia S , Angonese Cristine F , Menna-Barreto Sérgio
Published: May 2010

The objective of this study was to investigate the prevalence and severity of asthma, rhinitis, and atopic eczema in schoolchildren from southern Brazil. A cross-sectional study was carried out with the International Study of Asthma and Allergies in Childhood phase III written questionnaire. The questionnaire was self-applied by 2,948 randomly selected schoolchildren aged 13 to 14 years. The lifetime prevalence rates of symptoms were as follows: wheezing, 40.8%; rhinitis, 40.7%; eczema, 13.6%; self-reported asthma, 14.6%; rhinitis, 31.4%; eczema, 13.4%. Rhinitis was reported by 55% of adolescents with current asthma (60% females vs 46.9% males). Girls 13 to 14 years of age had higher prevalence rates of asthma, rhinitis, and eczema than boys had. Atopic eczema was reported by 42.7% of girls and 31.4% of boys with asthma. The prevalence rates were statistically significant for symptoms of asthma, rhinitis, and atopic eczema in females. However, there were no statistically significant differences between the sexes in regard to reported asthma and bronchospasm induced by exercise.
Lack of Correlation between Severity of Clinical Symptoms, Skin Test Reactivity, and Radioallergosorbent Test Results in Venom-Allergic Patients
Authors: Warrington R.J.
Published: May 2010

Purpose

To retrospectively examine the relation between skin test reactivity, venom-specific immunoglobulin E (IgE) antibody levels, and severity of clinical reaction in patients with insect venom allergy.

Method

Thirty-six patients (including 15 females) who presented with a history of allergic reactions to insect stings were assessed. The mean age at the time of the reactions was 33.4 ± 15.1 years (range, 4-76 years), and patients were evaluated 43.6 ± 90 months (range, 1-300 months) after the reactions. Clinical reactions were scored according to severity, from 1 (cutaneous manifestations only) to 3 (anaphylaxis with shock). These scores were compared to scores for skin test reactivity (0 to 5, indicating the log increase in sensitivity from 1 μg/mL to 0.0001 μg/mL) and radioallergosorbent test (RAST) levels (0 to 4, indicating venom-specific IgE levels, from undetectable to >17.5 kilounits of antigen per litre [kUA/L]).

Results

No correlation was found between skin test reactivity (Spearman's coefficient = 0.15, p = .377) or RAST level (Spearman's coefficient = 0.32, p = .061) and the severity of reaction. Skin test and RAST scores both differed significantly from clinical severity (p < .05), but there was a significant correlation between skin test reactivity and RAST score (p = .042). There was no correlation between skin test reactivity and time since reaction (Spearman's coefficient = 0.18, p = .294) nor between RAST and time since reaction (r = 0.1353, p = .438). Elimination of patients tested more than 12 months after their reaction still produced no correlation between skin test reactivity (p = .681) or RAST score (p = .183) and the severity of the clinical reaction.

Conclusion

In venom-allergic patients (in contrast to reported findings in cases of inhalant IgE-mediated allergy), there appears to be no significant correlation between the degree of skin test reactivity or levels of venom-specific IgE (determined by RAST) and the severity of the clinical reaction.
Nutrient control of eukaryote cell growth: a systems biology study in yeast
Authors: Gutteridge Alex , Pir Pınar , Castrillo Juan I , Charles Philip D , Lilley Kathryn S , Oliver Stephen G
Published: May 2010

Background

To elucidate the biological processes affected by changes in growth rate and nutrient availability, we have performed a comprehensive analysis of the transcriptome, proteome and metabolome responses of chemostat cultures of the yeast,Saccharomyces cerevisiae, growing at a range of growth rates and in four different nutrient-limiting conditions.

Results

We find significant changes in expression for many genes in each of the four nutrient-limited conditions tested. We also observe several processes that respond differently to changes in growth rate and are specific to each nutrient-limiting condition. These include carbohydrate storage, mitochondrial function, ribosome synthesis, and phosphate transport. Integrating transcriptome data with proteome measurements allows us to identify previously unrecognized examples of post-transcriptional regulation in response to both nutrient and growth-rate signals.

Conclusions

Our results emphasize the unique properties of carbon metabolism and the carbon substrate, the limitation of which induces significant changes in gene regulation at the transcriptional and post-transcriptional level, as well as altering how many genes respond to growth rate. By comparison, the responses to growth limitation by other nutrients involve a smaller set of genes that participate in specific pathways.

See associated commentaryhttp://www.biomedcentral.com/1741-7007/8/62
Prospective randomized trial evaluating mandatory second look surgery with HIPEC and CRS vs. standard of care in patients at high risk of developing colorectal peritoneal metastases
Authors: Ripley Robert T , Davis Jeremy L , Kemp Clinton D , Steinberg Seth M , Toomey Mary Ann , Avital Itzhak
Published: May 2010

Background

The standard of care for colorectal peritoneal carcinomatosis is evolving from chemotherapy to cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with disease limited to the peritoneum. Peritoneal carcinomatosis from colorectal cancer treated with chemotherapy alone results in median survival of 5 to 13 months, whereas CRS with HIPEC for early peritoneal carcinomatosis from colorectal cancer resulted in median survival of 48-63 months and 5 year survival of 51%.

Completeness of cytoreduction and limited disease are associated with longer survival, yet early peritoneal carcinomatosis is undetectable by conventional imaging. Exploratory laparotomy can successfully identify early disease, but this approach can only be justified in patients with high risk of peritoneal carcinomatosis. Historical data indicates that patients presenting with synchronous peritoneal carcinomatosis, ovarian metastases, perforated primary tumor, and emergency presentation with bleeding or obstructing lesions are at high risk of peritoneal carcinomatosis. Approximately 55% of these patient populations will develop peritoneal carcinomatosis. We hypothesize that performing a mandatory second look laparotomy with CRS and HIPEC for patients who are at high risk for developing peritoneal carcinomatosis from colorectal cancer will lead to improved survival as compared to patients who receive standard of care with routine surveillance.

Methods/Design

This study is a prospective randomized trial designed to answer the question whether mandatory second look surgery with CRS and HIPEC will prolong overall survival compared to the standard of care in patients who are at high risk for developing peritoneal carcinomatosis from colorectal cancer (CRC). Patients with CRC at high risk for developing peritoneal carcinomatosis who underwent curative surgery and subsequently received standard of care adjuvant chemotherapy will be evaluated. The patients who remain without evidence of disease by imaging, physical examination, and tumor markers for 12 months after the primary operation will be randomized to mandatory second look surgery or standard-of-care surveillance. At laparotomy, CRS and HIPEC will be performed with intraperitoneal oxaliplatin with concurrent systemic 5-fluorouracil and leucovorin. Up to 100 patients will be enrolled to allow for 35 evaluable patients in each arm; accrual is expected to last 5 years.

Trial Registration

ClinicalTrials.gov ID: NCT01095523
Clinical outcomes for T1-2N0-1 oral tongue cancer patients underwent surgery with and without postoperative radiotherapy
Authors: Shim Su Jung , Cha Jihye , Koom Woong Sub , Kim Gwi Eon , Lee Chang Geol , Choi Eun Chang , Keum Ki Chang
Published: May 2010

Background

The aim of this study was to assess the results of curative surgery with and without radiotherapy in patients with T1-2N0-1 oral tongue squamous cell carcinoma (OSCC) and to evaluate survival and prognostic factors.

Methods

Retrospective analysis of 86 patients with T1-2N0-1 OSCC who received surgery between January 2000 and December 2006. Fourteen patients (16.3%) received postoperative radiotherapy (PORT). Patient characteristics, tumor characteristics, treatment modality, failure patterns, and survival rates were analyzed.

Results

The median follow-up was 45 months. The five-year overall survival (OS) and disease-free survival (DFS) rates were 80.8% and 80.2%, respectively. Higher tumor grade and invasion depth ≥ 0.5 cm were the significant prognostic factors affecting five-year OS and DFS (OS rate; 65% vs. 91%, p = 0.001 for grade; 66% vs. 92%, p = 0.01 for invasion depth: DFS rate; 69% vs. 88%, p = 0.005 for grade; 66% vs. 92%, p = 0.013 for invasion depth). In the risk group, there was no local failure in patients with postoperative radiotherapy.

Conclusions

In T1-2N0-1 OSCC, factors that affected prognosis after primary surgery were higher tumor grade and deep invasion depth over 0.5 cm. Postoperative radiotherapy should be considered in early oral tongue cancer patients with these high-risk pathologic features.
Single column locking plate fixation is inadequate in two column acetabular fractures. A biomechanical analysis
Authors: Khajavi Kiarash , Lee Arthur T , Lindsey Derek P , Leucht Philipp , Bellino Michael J , Giori Nicholas J
Published: May 2010

Background

The objective of this study was to determine whether one can achieve stable fixation of a two column (transverse) acetabular fracture by only fixing a single column with a locking plate and unicortical locking screws. We hypothesized that a locking plate applied to the anterior column of a transverse acetabular fracture would create a construct that is more rigid than a non-locking plate, and that this construct would be biomechanically comparable to two column fixation.

Methods

Using urethane foam models of the pelvis, we simulated transverse acetabular fractures and stabilized them with 1) an anterior column plate with bicortical screws, 2) an anterior locking plate with unicortical screws, 3) an anterior plate and posterior column lag screw, and 4) a posterior plate with an anterior column lag screw. These constructs were mechanically loaded on a servohydraulic material testing machine. Construct stiffness and fracture displacement were measured.

Result and Discussion

We found that two column fixation is 54% stiffer than a single column fixation with a conventional plate with bicortical screws. There was no significant difference between fixation with an anterior column locking plate with unicortical screws and an anterior plate with posterior column lag screw. We detected a non-significant trend towards more stiffness for the anterior locking plate compared to the anterior non-locking plate.

Conclusion

In conclusion, a locking plate construct of the anterior column provides less stability than a traditional both column construct with posterior plate and anterior column lag screw. However, the locking construct offers greater strength than a non-locking, bicortical construct, which in addition often requires extensive contouring and its application is oftentimes accompanied by the risk of neurovascular damage.
Possible detection of cervical spondylotic neuropathy using Distribution of F-latency (DFL), a new neurophysiological parameter
Authors: Alam Mohammad J , Rabbani Khondkar S
Published: May 2010

Background

We have previously reported a new nerve conduction measurement parameter which we named the Distribution of F-latency (DFL) and showed that this was an approximate mirror of the Distribution of Conduction Velocity (DCV) of motor nerve fibers. This work was performed using measurements on the 20 median nerves from 10 volunteers. The DFL showed a number of different patterns including single peaks, broad peaks and double peaks, the latter observed on subjects with Cervical Spondylosis (CS). It was thought that a retrospective analysis of these data could be worthwhile in determining whether Cervical Spondylotic neuropathy could be detected using the DFL.

Findings

The DFL from the 8 median nerves of 4 normal subjects had single peaks, which has been assumed to represent a normal pattern. The DFL from one side of 5 subjects diagnosed with or suspected to have CS had double peaks. Broad peaks were observed in 7 nerves of which 5 were from subjects who had double peaks in the DFL on the contra lateral side.

Conclusions

Based on these findings, double peaks in the DFL appear to be associated with CS neuropathy. These findings further suggest that broad peaks in the DFL could indicate the early stages of the disease. Differential compression of nerve branches at the spinal roots are being explored as possible causes. This study does not preclude other pathologies contributing to double or broad peaks, but does suggest that the DFL could form a screening tool for CS neuropathy.
CaMKIV over-expression boosts cortical 4-7 Hz oscillations during learning and 1-4 Hz delta oscillations during sleep
Authors: Steenland Hendrik W , Wu Vincent , Fukushima Hotaka , Kida Satoshi , Zhuo Min
Published: May 2010

Mounting evidence suggests that neural oscillations are related to the learning and consolidation of newly formed memory in the mammalian brain. Four to seven Hertz (4-7 Hz) oscillations in the prefrontal cortex are also postulated to be involved in learning and attention processes. Additionally, slow delta oscillations (1-4 Hz) have been proposed to be involved in memory consolidation or even synaptic down scaling during sleep. The molecular mechanisms which link learning-related oscillations during wakefulness to sleep-related oscillations remain unknown. We show that increasing the expression of calcium/calmodulin dependent protein kinase IV (CaMKIV), a key nucleic protein kinase, selectively enhances 4-7.5 Hz oscillation power during trace fear learning and slow delta oscillations during subsequent sleep. These oscillations were found to be boosted in response to the trace fear paradigm and are likely to be localized to regions of the prefrontal cortex. Correlation analyses demonstrate that a proportion of the variance in 4-7.5 Hz oscillations, during fear conditioning, could account for some degree of learning and subsequent memory formation, while changes in slow delta power did not share this predictive strength. Our data emphasize the role of CaMKIV in controlling learning and sleep-related oscillations and suggest that oscillatory activity during wakefulness may be a relevant predictor of subsequent memory consolidation.
RNA interference suppression of mucin 5AC (MUC5AC) reduces the adhesive and invasive capacity of human pancreatic cancer cells
Authors: Yamazoe Sadaaki , Tanaka Hiroaki , Sawada Tetsuji , Amano Ryosuke , Yamada Nobuya , Ohira Masaichi , Hirakawa Kosei
Published: May 2010

Background

MUC5AC is a secretory mucin normally expressed in the surface muconous cells of stomach and bronchial tract. It has been known that MUC5AC de novo expression occurred in the invasive ductal carcinoma and pancreatic intraepithelial neoplasm with no detectable expression in normal pancreas, however, its function remains uncertain. Here, we report the impact of MUC5AC on the adhesive and invasive ability of pancreatic cancer cells.

Methods

We used two MUC5AC expressing cell lines derived from human pancreatic cancer, SW1990 and BxPC3. Small-interfering (si) RNA directed against MUC5AC were used to assess the effects of MUC5AC on invasion and adhesion of pancreas cancer cells in vitro and in vivo. We compared parental cells (SW1990 and BxPC3) with MUC5AC suppressed cells by si RNA (si-SW1990 and si-BxPC3).

Results

MUC5AC was found to express in more than 80% of pancreatic ductal carcinoma specimens. Next we observed that both of si-SW1990 and si-BxPC3 showed significantly lower adhesion and invasion to extracellular matrix components compared with parental cell lines. Expression of genes associated with adhesion and invasion including several integerins, matrix metalloproteinase (MMP) -3 and vascular endothelial growth factor (VEGF) were down-regulated in both MUC5AC suppressed cells. Furthermore, production of VEGF and phosphorylation of VEGFR-1 were significantly reduced by MUC5AC down regulation. Both of si-SW1990 and si-BxPC3 attenuated activation of Erk1/2. In vivo, si-SW1990 did not establish subcutaneous tumor in nude mice.

Conclusions

Knockdown of MUC5AC reduced the ability of pancreatic cancer cells to adhesion and invasion, suggesting that MUC5AC might contribute to the invasive motility of pancreatic cancer cells by enhancing the expression of integrins, MMP-3, VEGF and activating Erk pathway.
Breast cancer-specific mutations in CK1ε inhibit Wnt/β-catenin and activate the Wnt/Rac1/JNK and NFAT pathways to decrease cell adhesion and promote cell migration
Authors: Foldynová-Trantírková Silvie , Sekyrová Petra , Tmejová Kateřina , Brumovská Eva , Bernatík Ondřej , Blankenfeldt Wulf , Krejčí Pavel , Kozubík Alois , Doležal Tomáš , Trantírek Lukáš , Bryja Vítězslav
Published: May 2010

Introduction

Breast cancer is one of the most common types of cancer in women. One of the genes that were found mutated in breast cancer is casein kinase 1 epsilon (CK1ε). Because CK1ε is a crucial regulator of the Wnt signaling cascades, we determined how these CK1ε mutations interfere with the Wnt pathway and affect the behavior of epithelial breast cancer cell lines.

Methods

We performed in silico modeling of various mutations and analyzed the kinase activity of the CK1ε mutants both in vitro and in vivo. Furthermore, we used reporter and small GTPase assays to identify how mutation of CK1ε affects different branches of the Wnt signaling pathway. Based on these results, we employed cell adhesion and cell migration assays in MCF7 cells to demonstrate a crucial role for CK1ε in these processes.

Results

In silico modeling and in vivo data showed that autophosphorylation at Thr 44, a site adjacent to the breast cancer point mutations in the N-terminal lobe of human CK1ε, is involved in positive regulation of the CK1ε activity. Our data further demonstrate that, in mammalian cells, mutated forms of CK1ε failed to affect the intracellular localization and phosphorylation of Dvl2; we were able to demonstrate that CK1ε mutants were unable to enhance Dvl-induced TCF/LEF-mediated transcription, that CK1ε mutants acted as loss-of-function in the Wnt/β-catenin pathway, and that CK1ε mutants activated the noncanonical Wnt/Rac-1 and NFAT pathways, similar to pharmacological inhibitors of CK1. In line with these findings, inhibition of CK1 promoted cell migration as well as decreased cell adhesion and E-cadherin expression in the breast cancer-derived cell line MCF7.

Conclusions

In summary, these data suggest that the mutations of CK1ε found in breast cancer can suppress Wnt/β-catenin as well as promote the Wnt/Rac-1/JNK and Wnt/NFAT pathways, thus contributing to breast cancer development via effects on cell adhesion and migration. In terms of molecular mechanism, our data indicate that the breast cancer point mutations in the N-terminal lobe of CK1ε, which are correlated with decreased phosphorylation activities of mutated forms of CK1ε both in vitro and in vivo, interfere with positive autophosphorylation at Thr 44.
Medical resource utilization among patients with ventilator-associated pneumonia: pooled analysis of randomized studies of doripenem versus comparators
Authors: Kollef Marin H , Nathwani Dilip , Merchant Sanjay , Gast Christopher , Quintana Alvaro , Ketter Nzeera
Published: May 2010

Introduction

Ventilator-associated pneumonia (VAP) is associated with increased medical resource utilization, but few randomized studies have been conducted to evaluate the effect of initial antibiotic therapy. To assess medical resource utilization in patients with VAP, we conducted a pooled analysis of two prospective, randomized, open-label, multicenter, phase III studies, which also showed that doripenem was clinically noninferior to comparators.

Methods

We assessed durations of mechanical ventilation, intensive care unit (ICU) stay, and hospitalization in patients with VAP who received at least 1 dose of doripenem or a comparator in the phase III studies. Comparators were piperacillin/tazobactam (study 1) and imipenem (study 2). We analyzed between-group differences in medical resource utilization endpoints by comparison of Kaplan-Meier curves with generalized Wilcoxon test and in microbiologic eradication rates by two-sided Fisher's exact test.

Results

625 patients with VAP were evaluated and received at least 1 dose of doripenem (n = 312) or a comparator (n = 313). Median durations of mechanical ventilation (7 versus 10 days; P = 0.008) and hospitalization (22 versus 26 days; P = 0.010) were shorter for doripenem than comparators; corresponding ICU stays were 12 and 13 days (P = 0.065). All-cause, overall mortality rates were similar (51/312 [16%] versus 47/313 [15%]; P = 0.648). MIC90 values against Pseudomonas aeruginosa for doripenem versus imipenem were 4 versus 16 μg/mL in study 2. P. aeruginosa was eradicated from 16/24 (67%) doripenem recipients and 10/24 (42%) comparator recipients (P = 0.147). In patients with P. aeruginosa at baseline, median durations of mechanical ventilation (7 versus 13 days; P = 0.031) and ICU stay (13 versus 21 days; P = 0.027) were shorter for doripenem; corresponding hospital stays were 24 and 35 days (P = 0.129).

Conclusions

Doripenem was associated with lower medical resource utilization than comparators. Differences in antipseudomonal activity may have contributed to these findings.

Trial registration

ClinicalTrials.gov number NCT00211003 (study 1) and NCT00211016 (study 2).
Sex, Drugs, and Rock ‘n’ Roll: Caring for Adolescents and Young Adults With Cancer
Authors: Morgan Sue , Davies Simon , Palmer Susan , Plaster Meg
Published: May 2010

Adolescents and young adults (AYAs) with cancer are a distinct group whose needs have been poorly addressed within health care systems. This imbalance is being addressed in some countries, and this growing specialty is now receiving the recognition it requires in order to develop further. This article discusses some of the psychosocial issues of AYAs and, with reference to the phrase of sex, drugs, and rock and roll, highlights the various rites of passage that young people experience. It also discusses how services and professionals can work alongside AYAs, enabling them to feel a part of the process by providing age-appropriate environment and expertise.
Phase II Evaluation of Sorafenib in Advanced and Metastatic Squamous Cell Carcinoma of the Head and Neck: Southwest Oncology Group Study S0420
Authors: Williamson Stephen K. , Moon James , Huang Chao H. , Guaglianone Perry P. , LeBlanc Michael , Wolf Gregory T. , Urba Susan G.
Published: May 2010

Purpose

We conducted a phase II trial to evaluate the efficacy and safety of single-agent sorafenib in chemotherapy-naïve patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN). The primary end point was response probability (ie, confirmed complete and partial response [PR]).

Patients and Methods

Chemotherapy-naïve patients with metastatic, persistent, or recurrent SCCHN who received one induction or fewer or received an adjuvant chemotherapy regimen, who had adequate organ function, and who had a performance status ≤ 1 were eligible. Sorafenib was administered orally at 400 mg twice daily on a continuous basis in 28-day cycles. Responses were evaluated according to RECIST (Response Evaluation Criteria in Solid Tumors).

Results

Sorafenib was generally well tolerated. Of the 41 eligible patients assessed for adverse events, one experienced a grade 4 adverse event as a result of an asymptomatic pulmonary embolus. The most common grades 2 to 3 adverse events were fatigue, anorexia, stomatitis/oral pain, abdominal pain, hand-foot syndrome, weight loss, and hypertension. There was one confirmed PR and two unconfirmed PRs. The estimated confirmed response probability was 2% (95% CI, 0% to 13%). The estimated median progression-free survival was 4 months (95% CI, 2 to 4 months), and the estimated median overall survival was 9 months (95% CI, 7 to 14 months).

Conclusion

Sorafenib was well tolerated. Although response was poor, progression-free and overall survival times compare favorably with previous Southwest Oncology Group, phase II, single-agent trials.
Reliability of Human Epidermal Growth Factor Receptor 2 Immunohistochemistry in Breast Core Needle Biopsies
Authors: Lebeau Annette , Turzynski Andreas , Braun Susanne , Behrhof Wera , Fleige Barbara , Schmitt Wolfgang D. , Grob Tobias J. , Burkhardt Lia , Hölzel Dieter , Jackisch Christian , Thomssen Christoph , Müller Volkmar , Untch Michael
Published: May 2010

Purpose

Core needle biopsies (CNBs) are widely used to determine human epidermal growth factor receptor 2 (HER2) status in breast cancer. Recent publications reported up to 20% false-positive results on CNBs if immunohistochemistry (IHC) is compared with fluorescent in situ hybridization (FISH). To clarify, if confirmation of IHC positivity by FISH is generally required, we analyzed the reliability of IHC positivity on CNBs versus surgical specimens in a multi-institutional study.

Patients and Methods

Five pathologic laboratories contributed to this study by performing IHC on 500 CNBs and the corresponding surgical specimens overall. If IHC revealed score 2+ or 3+, HER2 status was confirmed by FISH in a central laboratory. We compared evaluation according to US Food and Drug Administration–approved scoring criteria and recently published American Society of Clinical Oncology (ASCO)–College of American Pathologists (CAP) guidelines.

Results

CNBs scored 3+ revealed five false-positive results if scoring followed the US Food and Drug Administration criteria (five of 40; 12.5%) and two false-positives in terms of the ASCO-CAP criteria (two of 33; 6.1%). IHC was false negative in one CNB only. By contrast, IHC on surgical specimens revealed five false-negative results, but only one false-positive result (one of 35; 2.9%) if scored following US Food and Drug Administration–approved criteria. With the aid of the ASCO-CAP criteria, false-positive IHC results were obtained in only one of the five participating institutions.

Conclusion

IHC 3+ scores on CNBs proved to be reliable in four of the five participating institutions if scoring followed the ASCO-CAP criteria. Therefore, accurate determination of HER2 status in breast cancer is possible on CNB using the common strategy to screen all cases by IHC and retest only 2+ scores by FISH. Prerequisites are quality assurance and the application of the new ASCO-CAP criteria.