bluuebunny/crossref_metadata_2025 huggingface dataset:
Burnt: Writing Torch Singers and Torch Singing
Authors: Holman Jones Stacy
Published: April 2010

This article responds to Phillip Auslander’s call for performance studies scholars to engage analyses of popular music performances, particularly those that consider the performers themselves. The author takes Auslander’s tripartite scheme for the performer—performance interaction as a starting point for looking at how torch singers and torch singing are heard, understood, fixed, loved, reviled, and dismissed. In contrast to musical performers and performances as conscious constructions of purposeful identities (separate from the musician as person), the torch singer and her performances are understood as an inevitable collapse of person, performance persona, and character. This is particularly evident in discussions of Billie Holiday’s performances of torch songs and the antilynching anthem “Strange Fruit,” as well as commentary on her love life and sexuality.
Storytelling in the Field: Race, Method, and the Empowerment of Latina College Students
Authors: Rodriguez Dalia
Published: April 2010

Scholars have raised questions about whether traditional methods are applicable or merely insufficient for studying racial and ethnic populations. There also remains a gap in addressing how race mediates the research process in qualitative research, particularly when researching Latina female college students. The author addresses how storytelling can serve as a means for researchers to create collective transformational spaces, coconstructing knowledge about self, further deepening our understandings about the role of race while in the field. There are three ways in which storytelling may serve to guide researchers when conducting research with students of color in particular. First, storytelling serves as a means to build deeper and more meaningful relationships with participants. Second, through storytelling, the researcher may disrupt racist messages that students of color often receive, particularly in predominantly White settings. Last, storytelling serves as a means for both researchers and participants to carve out spaces to share personal experiences about racism. When conducting research, scholars of color can draw on our particular racialized experiences, and through sharing our stories with marginalized students we can show empathy, allowing for participants to express themselves as racialized beings. Sharing these experiences not only help students cope with racism but also provides a space to affirm the lived experiences and knowledge of students of color. In this way, storytelling serves as a means of empowering students of color during the data-collection process.
Bronchial thermoplasty: a novel technique in the treatment of severe asthma
Authors: Castro Mario , Musani Ali I. , Mayse Martin L. , Shargill Narinder S.
Published: April 2010

New therapies are needed for patients with severe persistent asthma who cannot achieve control with current therapy of inhaled corticosteroids and long-acting β2-agonists. Bronchial thermoplasty is a novel intervention for asthma that delivers controlled thermal energy to the airway wall during a series of bronchoscopies, resulting in a prolonged reduction in airway smooth muscle mass. We review the method of performing bronchial thermoplasty with the Alair System, how to appropriately select and manage patients undergoing bronchial thermoplasty, and the clinical experience to date with this treatment. Randomized, controlled clinical trials with bronchial thermoplasty in subjects with severe asthma have resulted in improvements in overall asthma control as demonstrated by significant improvement in quality of life, asthma symptoms, severe exacerbations requiring corticosteroids, days lost from work/school/other daily activities due to asthma, and healthcare utilization.
Posterior Hip Pain in an Athletic Population: Differential Diagnosis and Treatment Options
Authors: Frank Rachel M. , Slabaugh Mark A. , Grumet Robert C. , Virkus Walter W. , Bush-Joseph Charles A. , Nho Shane J.
Published: April 2010

Context:

Posterior hip pain is a relatively uncommon but increasingly recognized complaint in the orthopaedic community. Patient complaints and presentations are often vague or nonspecific, making diagnosis and subsequent treatment decisions difficult. The purposes of this article are to review the anatomy and pathophysiology related to posterior hip pain in the athletic patient population.

Evidence Acquisition:

Data were collected through a thorough review of the literature via a MEDLINE search of all relevant articles between 1980 and 2010.

Results:

Many patients who complain of posterior hip pain actually have pain referred from another part of the body—notably, the lumbar spine or sacroiliac joint. Treatment options for posterior hip pain are typically nonoperative; however, surgery is warranted in some cases.

Conclusions:

Recent advancements in the understanding of hip anatomy, pathophysiology, and treatment options have enabled physicians to better diagnosis athletic hip injuries and select patients for appropriate treatment.
A Minimally Disruptive Surgical Technique for the Treatment of Osteitis Pubis in Athletes
Authors: Hechtman Keith S. , Zvijac John E. , Popkin Charles A. , Zych Gregory A. , Bemden Angie Botto-van
Published: April 2010

Background:

Multiple surgical procedures exist for the treatment of osteitis pubis: curettage of the symphysis joint, wedge resection, complete resection of the joint, placement of extraperitoneal retropubic synthetic mesh, and arthrodesis of the joint. However, a paucity of literature has reported long-term successful outcomes with the aforementioned approaches. Patients treated operatively have reported recalcitrant pain resulting from iatrogenic instability. The article presents the results of a conservative operative technique that avoids disruption of adjacent ligaments.

Hypothesis:

Preserving the adjacent ligamentous structures will allow competitive athletes to return to competition and activities of daily living free of iatrogenic pelvic instability and pain.

Study Design:

Case series.

Methods:

Four competitive athletes (2 professional and 2 collegiate football players) diagnosed with osteitis pubis were treated conservatively for a minimum of 6 months. Patients underwent surgical intervention upon failure to respond to nonoperative management. The degenerative tissue was resected, allowing only bleeding cancellous bone to remain while preserving the adjacent ligaments. An arthroscope was used to assist in curettage, allowing the debridement to be performed through a small incision in the anterior capsule.

Results:

The symptoms of all 4 patients resolved, and they returned to competitive athletics. This ligament-sparing technique provided a solid, stable repair and pain relief.

Conclusion:

This surgical technique preserves the adjacent ligamentous structures and allows competitive athletes to return to competition and activities of daily living free of pain and void of pelvic instability.

Clinical Relevance:

This technique is a surgical treatment option for athletes with osteitis pubis who fail conservative treatment.
Imaging of Sports-Related Hip and Groin Injuries
Authors: Lischuk Andrew W. , Dorantes Thomas M. , Wong William , Haims Andrew H.
Published: April 2010

A normally functioning hip joint is imperative for athletes who use their lower extremities with running, jumping, or kicking activities. Sports-related injuries of the hip and groin are far less frequent than injuries to the more distal aspect of the extremity, accounting for less than 10% of lower extremity injuries. Despite the lower incidence, hip and groin injuries can lead to significant clinical and diagnostic challenges related to the complex anatomy and biomechanical considerations of this region. Loads up to 8 times normal body weight have been documented in the joint in common daily activities, such as jogging, with significantly greater force expected during competitive athletics. Additionally, treatment for hip and groin injuries can obviate the participation of medical and surgical specialties, with a multidisciplinary approach frequently required. Delay in diagnosis and triage of these injuries may cause loss of time from competition and, potentially, early onset of degenerative changes. Magnetic resonance imaging (MRI) of the hip has proven to be the gold standard for the diagnosis of sports-related hip and groin injuries in the setting of negative radiographs. With its exquisite soft tissue contrast, multiplanar capabilities, and lack of ionizing radiation, MRI is unmatched in the noninvasive diagnosis of intra-articular and extra-articular pathology, as well as intraosseous processes. This review focuses on MRI of common athletic injuries of the hip and groin, including acetabular labral tears, femoral acetabular impingement syndrome, muscle injuries around the hip and groin (including athletic pubalgia), and athletic osseous injuries.
Groin Injuries in Sports Medicine
Authors: Tyler Timothy F. , Silvers Holly J. , Gerhardt Michael B. , Nicholas Stephen J.
Published: April 2010

Context:

An in-season groin injury may be debilitating for the athlete. Proper diagnosis and identification of the pathology are paramount in providing appropriate intervention. Furthermore, an adductor strain that is treated improperly can become chronic and career threatening. Any one of the 6 muscles of the adductor muscle group can be involved. The degree of injury can range from a minor strain (grade 1), where minimal playing time is lost, to a severe strain (grade 3), in which there is complete loss of muscle function. Persistent groin pain and muscle imbalance may lead to athletic pubalgia.

Evidence Acquisition:

Relevant studies were identified through a literature search of MEDLINE and the Cochrane database from 1990 to 2009, as well as a manual review of reference lists of identified sources.

Results:

Ice hockey and soccer players seem particularly susceptible to adductor muscle strains. In professional ice hockey and soccer players throughout the world, approximately 10% to 11% of all injuries are groin strains. These injuries have been linked to hip muscle weakness, a previous injury to that area, preseason practice sessions, and level of experience. This injury may be prevented if these risk factors are addressed before each season.

Conclusion:

Despite the identification of risk factors and strengthening intervention for athletes, adductor strains continue to occur throughout sport. If groin pain persists, the possibility of athletic pubalgia needs to be explored, because of weakening or tears in the abdominal wall muscles. A diagnosis is confirmed by exclusion of other pathology.
Impact of Asthma Self-management on Pediatric Emergency Department Visits and Hospitalizations
Authors: Tolomeo Concettina (Tina) , Savrin Carol , Heinzer Marjorie M.
Published: April 2010

Asthma education is an essential component of asthma management. Studies indicate a decrease in emergency department visits and hospitalizations when patients or parents participate in asthma self-management education programs. Because of time constraints, programs are often not offered or attended. Furthermore, variation among programs makes it difficult to generalize findings from one program to another. The purpose of this study was to compare the number of children who experienced an asthma-related emergency department visit and/or hospitalization between those whose parents attended a short, group-based, inpatient asthma self-management education program and those whose parents did not attend. A retrospective, comparative, descriptive study was conducted. Subjects consisted of a convenience sample of 298 children (attended, n = 126; did not attend, n = 172) admitted to a New England children’s hospital in 2006 with a primary diagnosis of asthma. Data from 2 hospital databases were collected for 12 months after attendance or nonattendance to the program. To compare the groups, basic descriptive statistics were followed by χ2 tests. There were no significant differences between the group whose parents attended the program and the group whose parents did not attend with regard to emergency department visits (attended, n = 36; did not attend, n = 54; P = .600) and hospitalizations (attended, n = 18; did not attend, n = 36; P = .141). Results support modifying the short, group-based inpatient asthma self-management education program examined in this study to include additional self-efficacy building strategies that promote enhanced self-management.
Virally infected and matured human dendritic cells activate natural killer cells via cooperative activity of plasma membrane-bound TNF and IL-15
Authors: Vujanovic Lazar , Szymkowski David E. , Alber Sean , Watkins Simon C. , Vujanovic Nikola L. , Butterfield Lisa H.
Published: April 2010

Recombinant adenovirus-engineered dendritic cells (Ad.DCs) are potent immunologic adjuvants of antiviral and anticancer vaccines. The effectiveness of Ad.DC-based vaccines may depend on the ability of Ad.DCs to crosstalk with natural killer (NK) cells and to activate, polarize, and bridge innate and adaptive immunity. We investigated, for the first time, whether and how human Ad.DCs activate NK cells, and compared the Ad.DC function with that of immature DCs and matured DCs (mDCs). We found that adenovirus transduction and lipopolysaccharide/interferon-γ-induced maturation increased expression of transmembrane tumor necrosis factor (TNF) and trans-presented (trans) interleukin-15 (IL-15) on DCs, leading to enhanced NK cell activation without enhancing DC susceptibility to NK cell-mediated killing. This crosstalk enhanced NK cell CD69 expression, interferon-γ secretion, proliferation, and antitumor activities, with Ad.DCs being significantly more effective than immature DCs, but less effective than mDCs. The Ad.DC and mDC crosstalk with NK cells was largely prevented by physical separation of DCs and NK cells, and neutralization of total TNF and IL-15, but not by selective sequestration of soluble TNF. These findings demonstrate that both Ad.DCs and mDCs can efficiently promote innate immune functions by activation of NK cells through the cooperative activities of tmTNF and trans-IL-15 mediated by cell-to-cell contact.
Treatment with Imiquimod enhances antitumor immunity induced by therapeutic HPV DNA vaccination
Authors: Chuang Chi-Mu , Monie Archana , Hung Chien-Fu , Wu T-C
Published: April 2010

Background

There is an urgent need to develop new innovative therapies for the control of advanced cancer. The combination of antigen-specific immunotherapy with the employment of immunomodulatory agents has emerged as a potentially plausible approach for the control of advanced cancer.

Methods

In the current study, we explored the combination of the DNA vaccine encoding calreticulin (CRT) linked to human papillomavirus type 16 (HPV-16) E7 antigen (CRT/E7) with the TLR7 agonist imiquimod for their ability to generate E7-specific immune responses and antitumor effects in tumor-bearing mice.

Results

We observed that treatment with CRT/E7 DNA in combination with imiquimod leads to an enhancement in the E7-specific CD8+ T cell immune responses and a decrease in the number of myeloid-derived suppressor cells in the tumor microenvironment of tumor-bearing mice. Furthermore, treatment with CRT/E7 DNA in combination with imiquimod leads to significantly improved antitumor effects and prolonged survival in treated mice. In addition, treatment with imiquimod led to increased number of NK1.1+ cells and F4/80+ cells in the tumor microenvironment. Macrophages and NK1.1+ cells were found to play an important role in the antitumor effects mediated by treatment with CRT/E7 DNA in combination with imiquimod.

Conclusions

Thus, our data suggests that the combination of therapeutic HPV DNA vaccination with topical treatment with the TLR7 agonist imiquimod enhances the antitumor immunity induced by DNA vaccination. The current study has significant implications for future clinical translation.
Bomapin is a redox-sensitive nuclear serpin that affects responsiveness of myeloid progenitor cells to growth environment
Authors: Przygodzka Patrycja , Ramstedt Björn , Tengel Tobias , Larsson Göran , Wilczynska Malgorzata
Published: April 2010

Background

Haematopoiesis is a process of formation of mature blood cells from hematopoietic progenitors in bone marrow. Haematopoietic progenitors are stimulated by growth factors and cytokines to proliferate and differentiate, and they die via apoptosis when these factors are depleted. An aberrant response to growth environment may lead to haematological disorders. Bomapin (serpinb10) is a hematopoietic- and myeloid leukaemia-specific protease inhibitor with unknown function.

Results

We found that the majority of naturally expressed bomapin was located in the nucleus. Both the natural and recombinant bomapin had a disulfide bond which linked the only two bomapin cysteines: one located in the CD-loop and the other near the C-terminus. Computer modelling showed that the cysteines are distant in the reduced bomapin, but can easily be disulfide-linked without distortion of the overall bomapin structure. Low-level ectopic expression of bomapin in bomapin-deficient K562 cells resulted in about 90% increased cell proliferation under normal growth conditions. On the other hand, antisense-downregulation of natural bomapin in U937 cells resulted in a decreased cell proliferation. Bomapin C395S mutant, representing the reduced form of the serpin, had no effect on cell proliferation, suggesting that the disulfide bond-linked conformation of bomapin is biologically important. The bomapin-dependent effect was specific for myeloid cells, since ectopic expression of the serpin in HT1080 cells did not change cell proliferation. In contrast to the survival-promoting activity of bomapin in cells cultured under optimal growth conditions, bomapin enhanced cell apoptosis following growth factor withdrawal.

Conclusions

We propose that bomapin is a redox-sensitive nuclear serpin that augments proliferation or apoptosis of leukaemia cells, depending on growth factors availability.
Human intronic enhancers control distinct sub-domains of Gli3 expression during mouse CNS and limb development
Authors: Abbasi Amir A , Paparidis Zissis , Malik Sajid , Bangs Fiona , Schmidt Ansgar , Koch Sabine , Lopez-Rios Javier , Grzeschik Karl-Heinz
Published: April 2010

Background

The zinc-finger transcription factor GLI3 is an important mediator of Sonic hedgehog signaling and crucial for patterning of many aspects of the vertebrate body plan. In vertebrates, the mechanism of SHH signal transduction and its action on target genes by means of activating or repressing forms of GLI3 have been studied most extensively during limb development and the specification of the central nervous system. From these studies it has emerged, that Gli3 expression must be subject to a tight spatiotemporal regulation. However, the genetic mechanisms and the cis-acting elements controlling the expression of Gli3 remained largely unknown.

Results

Here, we demonstrate in chicken and mouse transgenic embryos that human GLI3-intronic conserved non-coding sequence elements (CNEs) autonomously control individual aspects of Gli3 expression. Their combined action shows many aspects of a Gli3-specific pattern of transcriptional activity. In the mouse limb bud, different CNEs enhance Gli3-specific expression in evolutionary ancient stylopod and zeugopod versus modern skeletal structures of the autopod. Limb bud specificity is also found in chicken but had not been detected in zebrafish embryos. Three of these elements govern central nervous system specific gene expression during mouse embryogenesis, each targeting a subset of endogenous Gli3 transcription sites. Even though fish, birds, and mammals share an ancient repertoire of gene regulatory elements within Gli3, the functions of individual enhancers from this catalog have diverged significantly. During evolution, ancient broad-range regulatory elements within Gli3 attained higher specificity, critical for patterning of more specialized structures, by abolishing the potential for redundant expression control.

Conclusion

These results not only demonstrate the high level of complexity in the genetic mechanisms controlling Gli3 expression, but also reveal the evolutionary significance of cis-acting regulatory networks of early developmental regulators in vertebrates.
Screening mutations in myosin binding protein C3 gene in a cohort of patients with Hypertrophic Cardiomyopathy
Authors: Rodríguez-García María Isabel , Monserrat Lorenzo , Ortiz Martín , Fernández Xusto , Cazón Laura , Núñez Lucía , Barriales-Villa Roberto , Maneiro Emilia , Veira Elena , Castro-Beiras Alfonso , Hermida-Prieto Manuel
Published: April 2010

Background

MyBPC3 mutations are amongst the most frequent causes of hypertrophic cardiomyopathy, however, its prevalence varies between populations. They have been associated with mild and late onset disease expression. Our objectives were to establish the prevalence of MyBPC3 mutations and determine their associated clinical characteristics in our patients.

Methods

Screening by Single Strand Conformation Polymorphisms (SSCP) and sequencing of the fragments with abnormal motility of the MyBPC3 gene in 130 unrelated consecutive HCM index cases. Genotype-Phenotype correlation studies were done in positive families.

Results

16 mutations were found in 20 index cases (15%): 5 novel [D75N, V471E, Q327fs, IVS6+5G>A (homozygous), and IVS11-9G>A] and 11 previously described [A216T, R495W, R502Q (2 families), E542Q (3 families), T957S, R1022P (2 families), E1179K, K504del, K600fs, P955fs and IVS29+5G>A]. Maximum wall thickness and age at time of diagnosis were similar to patients with MYH7 mutations [25(7) vs. 27(8), p = 0.16], [46(16) vs. 44(19), p = 0.9].

Conclusions

Mutations in MyBPC3 are present in 15% of our hypertrophic cardiomyopathy families. Severe hypertrophy and early expression are compatible with the presence of MyBPC3 mutations. The genetic diagnosis not only allows avoiding clinical follow up of non carriers but it opens new possibilities that includes: to take preventive clinical decisions in mutation carriers than have not developed the disease yet, the establishment of genotype-phenotype relationship, and to establish a genetic diagnosis routine in patients with familial HCM.
Clinical significance of Phosphatidyl Inositol Synthase overexpression in oral cancer
Authors: Kaur Jatinder , Sawhney Meenakshi , DattaGupta Siddartha , Shukla Nootan K , Srivastava Anurag , Ralhan Ranju
Published: April 2010

Background

We reported increased levels of Phosphatidyl Inositol synthase (PI synthase), (enzyme that catalyses phosphatidyl inositol (PI) synthesis-implicated in intracellular signaling and regulation of cell growth) in smokeless tobacco (ST) exposed oral cell cultures by differential display. This study determined the clinical significance of PI synthase overexpression in oral squamous cell carcinoma (OSCC) and premalignant lesions (leukoplakia), and identified the downstream signaling proteins in PI synthase pathway that are perturbed by smokeless tobacco (ST) exposure.

Methods

Tissue microarray (TMA) Immunohistochemistry, Western blotting, Confocal laser scan microscopy, RT-PCR were performed to define the expression of PI synthase in clinical samples and in oral cell culture systems.

Results

Significant increase in PI synthase immunoreactivity was observed in premalignant lesions and OSCCs as compared to oral normal tissues (p = 0.000). Further, PI synthase expression was significantly associated with de-differentiation of OSCCs, (p = 0.005) and tobacco consumption (p = 0.03, OR = 9.0). Exposure of oral cell systems to smokeless tobacco (ST) in vitro confirmed increase in PI synthase, Phosphatidylinositol 3-kinase (PI3K) and cyclin D1 levels.

Conclusion

Collectively, increased PI synthase expression was found to be an early event in oral cancer and a target for smokeless tobacco.
Meta-analysis of archived DNA microarrays identifies genes regulated by hypoxia and involved in a metastatic phenotype in cancer cells
Authors: Pierre Michael , DeHertogh Benoît , Gaigneaux Anthoula , DeMeulder Bertrand , Berger Fabrice , Bareke Eric , Michiels Carine , Depiereux Eric
Published: April 2010

Background

Metastasis is a major cancer-related cause of death. Recent studies have described metastasis pathways. However, the exact contribution of each pathway remains unclear. Another key feature of a tumor is the presence of hypoxic areas caused by a lack of oxygen at the center of the tumor. Hypoxia leads to the expression of pro-metastatic genes as well as the repression of anti-metastatic genes. As many Affymetrix datasets about metastasis and hypoxia are publicly available and not fully exploited, this study proposes to re-analyze these datasets to extract new information about the metastatic phenotype induced by hypoxia in different cancer cell lines.

Methods

Affymetrix datasets about metastasis and/or hypoxia were downloaded from GEO and ArrayExpress. AffyProbeMiner and GCRMA packages were used for pre-processing and the Window Welchttest was used for processing. Three approaches of meta-analysis were eventually used for the selection of genes of interest.

Results

Three complementary approaches were used, that eventually selected 183 genes of interest. Out of these 183 genes, 99, among which the well knownJUNB,FOSandTP63, have already been described in the literature to be involved in cancer. Moreover, 39 genes of those, such asSERPINE1andMMP7, are known to regulate metastasis. Twenty-one genes includingVEGFAandID2have also been described to be involved in the response to hypoxia. Lastly, DAVID classified those 183 genes in 24 different pathways, among which 8 are directly related to cancer while 5 others are related to proliferation and cell motility. A negative control composed of 183 random genes failed to provide such results. Interestingly, 6 pathways retrieved by DAVID with the 183 genes of interest concern pathogen recognition and phagocytosis.

Conclusion

The proposed methodology was able to find genes actually known to be involved in cancer, metastasis and hypoxia and, thus, we propose that the other genes selected based on the same methodology are of prime interest in the metastatic phenotype induced by hypoxia.
Higher expression levels of SOCS 1,3,4,7 are associated with earlier tumour stage and better clinical outcome in human breast cancer
Authors: Sasi Walid , Jiang Wen G , Sharma Anup , Mokbel Kefah
Published: April 2010

Background

Suppressors of cytokine signaling (SOCS) are important negative feedback regulators of the JAK/STAT signaling pathway, and have been recently investigated for their role in the development of different cancers. In this study, we examined the expression of SOCS1-7 genes in normal and breast cancer tissue and correlated this with several clinico-pathological and prognostic factors.

Methods

SOCS1-7 mRNA extraction and reverse transcription were performed on fresh frozen breast cancer tissue samples (n = 127) and normal background breast tissue (n = 31). Transcript levels of expression were determined using real-time PCR and analyzed against TNM stage, tumour grade and clinical outcome over a 10 year follow-up period.

Results

SOCS1,4,5,6 and 7 expression decreased with increased TNM stage (TNM1 vs. TNM3 p = 0.039, TNM1 vs. TNM4 p = 0.016, TNM2 vs. TNM4 p = 0.025, TNM1 vs. TNM3 p = 0.012, and TNM1 vs. TNM3 p = 0.044 respectively). SOCS2 and 3 expression decreased with increased Nottingham Prognostic Index (NPI) (NPI1 vs. NPI3 p = 0.033, and NPI2 vs. NPI3 p = 0.041 respectively). SOCS7 expression decreased with higher tumour grade (Grade 3 vs. Grade 2 p = 0.037). After a median follow up period of 10 years, we found higher levels of SOCS1,2 and 7 expression among those patients who remained disease-free compared to those who developed local recurrence (p = 0.0073, p = 0.021, and p = 0.039 respectively). Similarly, we found higher levels of SOCS 2,4, and 7 expression in those who remained disease-free compared to those who developed distant recurrence (p = 0.022, p = 0.024, and p = 0.033 respectively). Patients who remained disease-free had higher levels of SOCS1 and 2 expression compared to those who died from breast cancer (p = 0.02 and p = 0.033 respectively). The disease free survival (DFS) and overall survival (OS) curves showed that higher levels of SOCS1, 3 and 7 were significant predictors of higher DFS (p = 0.015, p = 0.024 and 0.03 respectively) and OS (p = 0.005, p = 0.013 and p = 0.035 respectively). Higher levels of SOCS 4 were significant in predicting better OS (p = 0.007) but not DFS. Immunohistochemical staining of representative samples showed a correlation between SOCS1, 3, 7 protein staining and the SOCS1, 3, 7 mRNA expression.

Conclusion

Higher mRNA expression levels of SOCS1, 3, 4 and 7 are significantly associated with earlier tumour stage and better clinical outcome in human breast cancer.
Blechnum Orientale Linn - a fern with potential as antioxidant, anticancer and antibacterial agent
Authors: Lai How Y , Lim Yau Y , Kim Kah H
Published: April 2010

Background

Blechnum orientale Linn. (Blechnaceae) is used ethnomedicinally for the treatment of various skin diseases, stomach pain, urinary bladder complaints and sterilization of women. The aim of the study was to evaluate antioxidant, anticancer and antibacterial activity of five solvent fractions obtained from the methanol extract of the leaves of Blechnum orientale Linn.

Methods

Five solvent fractions were obtained from the methanol extract of B. orientale through successive partitioning with petroleum ether, chloroform, ethyl acetate, butanol and water. Total phenolic content was assessed using Folin-Ciocalteu's method. The antioxidant activity was determined by measuring the scavenging activity of DPPH radicals. Cytotoxic activity was tested against four cancer cell lines and a non-malignant cell using MTT assay. Antibacterial activity was assessed using the disc diffusion and broth microdilution assays. Standard phytochemical screening tests for saponins, tannins, terpenoids, flavonoids and alkaloids were also conducted.

Results

The ethyl acetate, butanol and water fractions possessed strong radical scavenging activity (IC50 8.6-13.0 μg/ml) and cytotoxic activity towards human colon cancer cell HT-29 (IC50 27.5-42.8 μg/ml). The three extracts were also effective against all Gram-positive bacteria tested: Bacillus cereus, Micrococcus luteus, methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA) and Stapylococcus epidermidis(minimum inhibitory concentration MIC 15.6-250 μg/ml; minimum bactericidal concentration MBC 15.6-250 μg/ml). Phytochemical analysis revealed the presence of flavonoids, terpenoids and tannins. Ethyl acetate and butanol fractions showed highest total phenolic content (675-804 mg gallic acid equivalent/g).

Conclusions

The results indicate that this fern is a potential candidate to be used as an antioxidant agent, for colon cancer therapy and for treatment of MRSA infections and other MSSA/Gram-positive bacterial infectious diseases.
NF-κB/STAT3/PI3K signaling crosstalk in iMycEμ B lymphoma
Authors: Han Seong-Su , Yun Hwakyung , Son Dong-Ju , Tompkins Van S. , Peng Liangping , Chung Seung-Tae , Kim Joong-Su , Park Eun-Sung , Janz Siegfried
Published: April 2010

Background

Myc is a well known driver of lymphomagenesis, and Myc-activating chromosomal translocation is the recognized hallmark of Burkitt lymphoma, an aggressive form of non-Hodgkin's lymphoma. We developed a model that mimics this translocation event by inserting a mouse Myc cDNA gene into the immunoglobulin heavy chain locus, just upstream of the intronic Eμ enhancer. These mice, designated iMycEμ, readily develop B-cell lymphoma. To study the mechanism of Myc-induced lymphoma, we analyzed signaling pathways in lymphoblastic B-cell lymphomas (LBLs) from iMycEμ mice, and an LBL-derived cell line, iMycEμ-1.

Results

Nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) were constitutively activated in iMycEμ mice, not only in LBLs but also in the splenic B-lymphocytes of young animals months before tumors developed. Moreover, inhibition of either transcription factor in iMycEμ-1 cells suppressed growth and caused apoptosis, and the abrogation of NF-κB activity reduced DNA binding by both STAT3 and Myc, as well as Myc expression. Inhibition of STAT3 signaling eliminated the activity of both NF-κB and Myc, and resulted in a corresponding decrease in the level of Myc. Thus, in iMycEμ-1 cells NF-κB and STAT3 are co-dependent and can both regulate Myc. Consistent with this, NF-κB and phosphorylated STAT3 were physically associated with one another. In addition, LBLs and iMycEμ-1 cells also showed constitutive AKT phosphorylation. Blocking AKT activation by inhibiting PI3K reduced iMycEμ-1 cell proliferation and caused apoptosis, via downregulation of NF-κB and STAT3 activity and a reduction of Myc levels. Co-treatment with NF-κB, STAT3 or/and PI3K inhibitors led to additive inhibition of iMycEμ-1 cell proliferation, suggesting that these signaling pathways converge.

Conclusions

Our findings support the notion that constitutive activation of NF-κB and STAT3 depends on upstream signaling through PI3K, and that this activation is important for cell survival and proliferation, as well as for maintaining the level of Myc. Together, these data implicate crosstalk among NF-κB, STAT3 and PI3K in the development of iMycEμ B-cell lymphomas.
Non-homologous isofunctional enzymes: A systematic analysis of alternative solutions in enzyme evolution
Authors: Omelchenko Marina V , Galperin Michael Y , Wolf Yuri I , Koonin Eugene V
Published: April 2010

Background

Evolutionarily unrelated proteins that catalyze the same biochemical reactions are often referred to as analogous - as opposed to homologous - enzymes. The existence of numerous alternative, non-homologous enzyme isoforms presents an interesting evolutionary problem; it also complicates genome-based reconstruction of the metabolic pathways in a variety of organisms. In 1998, a systematic search for analogous enzymes resulted in the identification of 105 Enzyme Commission (EC) numbers that included two or more proteins without detectable sequence similarity to each other, including 34 EC nodes where proteins were known (or predicted) to have distinct structural folds, indicating independent evolutionary origins. In the past 12 years, many putative non-homologous isofunctional enzymes were identified in newly sequenced genomes. In addition, efforts in structural genomics resulted in a vastly improved structural coverage of proteomes, providing for definitive assessment of (non)homologous relationships between proteins.

Results

We report the results of a comprehensive search for non-homologous isofunctional enzymes (NISE) that yielded 185 EC nodes with two or more experimentally characterized - or predicted - structurally unrelated proteins. Of these NISE sets, only 74 were from the original 1998 list. Structural assignments of the NISE show over-representation of proteins with the TIM barrel fold and the nucleotide-binding Rossmann fold. From the functional perspective, the set of NISE is enriched in hydrolases, particularly carbohydrate hydrolases, and in enzymes involved in defense against oxidative stress.

Conclusions

These results indicate that at least some of the non-homologous isofunctional enzymes were recruited relatively recently from enzyme families that are active against related substrates and are sufficiently flexible to accommodate changes in substrate specificity.

Reviewers

This article was reviewed by Andrei Osterman, Keith F. Tipton (nominated by Martijn Huynen) and Igor B. Zhulin. For the full reviews, go to the Reviewers' comments section.
Brain perfusion in fibromyalgia patients and its differences between responders and poor responders to gabapentin
Authors: Usui Chie , Hatta Kotaro , Doi Nagafumi , Nakanishi Atsushi , Nakamura Hiroyuki , Nishioka Kusuki , Arai Heii
Published: April 2010

Introduction

The aim of the present study was to determine the brain areas associated with fibromyalgia, and whether pretreatment regional cerebral blood flow (rCBF) can predict response to gabapentin treatment.

Methods

A total of 29 women with fibromyalgia and 10 healthy women (without pain) matched for age were finally enrolled in the study. Technetium-99m ethyl cysteinate dimer single photon emission computed tomography (99mTc-ECD SPECT) was performed in the fibromyalgia patients and controls. A voxel-by-voxel group analysis was performed using Statistic Parametric Mapping 5 (SPM5). After treatment with gabapentin, 16 patients were considered 'responders', with decrease in pain of greater than 50% as evaluated by visual analogue scale (VAS). The remaining 13 patients were considered 'poor responders'.

Results

We observed rCBF abnormalities, compared to control subjects, in fibromyalgia including hypoperfusion in the left culmen and hyperperfusion in the right precentral gyrus, right posterior cingulate, right superior occipital gyrus, right cuneus, left inferior parietal lobule, right middle temporal gyrus, left postcentral gyrus, and left superior parietal lobule. Compared to responders, poor responders exhibited hyperperfusion in the right middle temporal gyrus, left middle frontal gyrus, left superior frontal gyrus, right postcentral gyrus, right precuneus, right cingulate, left middle occipital gyrus, and left declive. The right middle temporal gyrus, left superior frontal gyrus, right precuneus, left middle occipital gyrus, and left declive exhibited high positive likelihood ratios.

Conclusions

The present study revealed brain regions with significant hyperperfusion associated with the default-mode network, in addition to abnormalities in the sensory dimension of pain processing and affective-attentional areas in fibromyalgia patients. Furthermore, hyperperfusion in these areas was strongly predictive of poor response to gabapentin.
A recruitment maneuver increases oxygenation after intubation of hypoxemic intensive care unit patients: a randomized controlled study
Authors: Constantin Jean-Michel , Futier Emmanuel , Cherprenet Anne-Laure , Chanques Gérald , Guerin Renaud , Cayot-Constantin Sophie , Jabaudon Mathieu , Perbet Sebastien , Chartier Christian , Jung Boris , Guelon Dominique , Jaber Samir , Bazin Jean-Etienne
Published: April 2010

Introduction

Tracheal intubation and anaesthesia promotes lung collapse and hypoxemia. In acute lung injury patients, recruitment maneuvers (RMs) increase lung volume and oxygenation, and decrease atelectasis. The aim of this study was to evaluate the efficacy and safety of RMs performed immediately after intubation.

Methods

This randomized controlled study was conducted in two 16-bed medical-surgical intensive care units within the same university hospital. Consecutive patients requiring intubation for acute hypoxemic respiratory failure were included. Patients were randomized to undergo a RM immediately (within 2 minutes) after intubation, consisting of a continuous positive airway pressure (CPAP) of 40 cmH2O over 30 seconds (RM group), or not (control group). Blood gases were sampled and blood samples taken for culture before, within 2 minutes, 5 minutes, and 30 minutes after intubation. Haemodynamic and respiratory parameters were continuously recorded throughout the study. Positive end expiratory pressure (PEEP) was set at 5 cmH2O throughout.

Results

The control (n = 20) and RM (n = 20) groups were similar in terms of age, disease severity, diagnosis at time of admission, and PaO2 obtained under 10-15 L/min oxygen flow immediately before (81 ± 15 vs 83 ± 35 mmHg, P = 0.9), and within 2 minutes after, intubation under 100% FiO2 (81 ± 15 vs 83 ± 35 mmHg, P = 0.9). Five minutes after intubation, PaO2 obtained under 100% FiO2 was significantly higher in the RM group compared with the control group (93 ± 36 vs 236 ± 117 mmHg, P = 0.008). The difference remained significant at 30 minutes with 110 ± 39 and 180 ± 79 mmHg, respectively, for the control and RM groups. No significant difference in haemodynamic conditions was observed between groups at any time. Following tracheal intubation, 15 patients had positive blood cultures, showing microorganisms shared with tracheal aspirates, with no significant difference in the incidence of culture positivity between groups.

Conclusions

Recruitment maneuver following intubation in hypoxemic patients improved short-term oxygenation, and was not associated with increased adverse effects.

Trial registration

NCT01014299
Group cognitive–behavioural therapy for anxiety and depression
Authors: Whitfield Graeme
Published: April 2010

Cognitive–behavioural therapy (CBT) is a psychological treatment approach that can be delivered not only on a one-to-one basis but also to groups and in self-help formats. However, the evidence base supporting individual CBT is more extensive than the research regarding group CBT. This is likely to influence the choice of services that develop in the Improving Access to Psychological Therapies (IAPT) programme for the treatment of depression and anxiety disorders in primary care in England. This article outlines the different forms that group CBT takes, the way in which it may benefit people and the current evidence base supporting its use for anxiety and depression. It also outlines the advantages of group or individual CBT and describes those patients who appear to be best suited to a specific delivery.
Effect of early intervention on 5-year outcome in non-affective psychosis
Authors: Gafoor Rafael , Nitsch Dorothea , McCrone Paul , Craig Tom K. J. , Garety Philippa A. , Power Paddy , McGuire Philip
Published: April 2010

Background

Early specialised care may improve short-term outcome in first-episode non-affective psychosis, but it is unclear if these benefits endure.

Aims

To assess the long-term effect of early intervention in psychosis.

Method

Individuals with first-episode psychosis were randomised to specialised care or care as usual (trial number: ISRCTN73679874). Outcome after 5 years was assessed by case-note review.

Results

There were no significant differences in the admission rate (coefficient 0.096, 95% CI −0.550 to 0.742, P = 0.770) or the mean number of bed days (coefficient 6.344, 95% CI −46 to 58.7, P = 0.810).

Conclusions

These findings that specialist intervention did not markedly improved outcome at 5 years accord with those from a larger OPUS study. The sample size of this study was small and these results should be generalised with caution. More research is needed.
Cost-effectiveness of psychotherapy for cluster B personality disorders
Authors: Soeteman Djøra I. , Verheul Roel , Delimon Jos , Meerman Anke M. M. A. , van den Eijnden Ellen , Rossum Bert V. , Ziegler Uli , Thunnissen Moniek , Busschbach Jan J. V. , Kim Jane J.
Published: April 2010

Background

Recommendations on current clinical guidelines are informed by limited economic evidence.

Aims

A formal economic evaluation of three modalities of psychotherapy for patients with cluster B personality disorders.

Method

A probabilistic decision-analytic model to assess the cost-effectiveness of out-patient, day hospital and in-patient psychotherapy over 5 years in terms of cost per recovered patient-year and cost per quality-adjusted life-year (QALY). Analyses were conducted from both societal and payer perspectives.

Results

From the societal perspective, the most cost-effective choice switched from out-patient to day hospital psychotherapy at a threshold of €12 274 per recovered patient-year; and from day hospital to in-patient psychotherapy at €113 298. In terms of cost per QALY, the optimal strategy changed at €56 325 and €286 493 per QALY respectively. From the payer perspective, the switch points were at €9895 and €155 797 per recovered patient-year, and €43 427 and €561 188 per QALY.

Conclusions

Out-patient psychotherapy and day hospital psychotherapy are the optimal treatments for patients with cluster B personality disorders in terms of cost per recovered patient-year and cost per QALY.
Notch signaling, wt1 and foxc2 are key regulators of the podocyte gene regulatory network in Xenopus
Authors: White Jeffrey T. , Zhang Bo , Cerqueira Débora M. , Tran Uyen , Wessely Oliver
Published: April 2010

Podocytes are highly specialized cells in the vertebrate kidney. They participate in the formation of the size-exclusion barrier of the glomerulus/glomus and recruit mesangial and endothelial cells to form a mature glomerulus. At least six transcription factors (wt1, foxc2, hey1, tcf21, lmx1b and mafb) are known to be involved in podocyte specification, but how they interact to drive the differentiation program is unknown. The Xenopus pronephros was used as a paradigm to address this question. All six podocyte transcription factors were systematically eliminated by antisense morpholino oligomers. Changes in the expression of the podocyte transcription factors and of four selected markers of terminal differentiation (nphs1, kirrel, ptpru and nphs2) were analyzed by in situ hybridization. The data were assembled into a transcriptional regulatory network for podocyte development. Although eliminating the six transcription factors individually interfered with aspects of podocyte development, no single gene regulated the entire differentiation program. Only the combined knockdown of wt1 and foxc2 resulted in a loss of all podocyte marker gene expression. Gain-of-function studies showed that wt1 and foxc2 were sufficient to increase podocyte gene expression within the glomus proper. However, the combination of wt1, foxc2 and Notch signaling was required for ectopic expression in ventral marginal zone explants. Together, this approach demonstrates how complex interactions are required for the correct spatiotemporal execution of the podocyte gene expression program.
Lipid phosphate phosphatase activity regulates dispersal and bilateral sorting of embryonic germ cells in Drosophila
Authors: Renault Andrew D. , Kunwar Prabhat S. , Lehmann Ruth
Published: April 2010

In Drosophila, germ cell survival and directionality of migration are controlled by two lipid phosphate phosphatases (LPP), wunen (wun) and wunen-2 (wun2). wun wun2 double mutant analysis reveals that the two genes, hereafter collectively called wunens, act redundantly in primordial germ cells. We find that wunens mediate germ cell-germ cell repulsion and that this repulsion is necessary for germ cell dispersal and proper transepithelial migration at the onset of migration and for the equal sorting of the germ cells between the two embryonic gonads during their migration. We propose that this dispersal function optimizes adult fecundity by assuring maximal germ cell occupancy of both gonads. Furthermore, we find that the requirement for wunens in germ cell survival can be eliminated by blocking germ cell migration. We suggest that this essential function of Wunen is needed to maintain cell integrity in actively migrating germ cells.