bluuebunny/crossref_metadata_2025 huggingface dataset:
Overexpression of biotin synthase and biotin ligase is required for efficient generation of sulfur-35 labeled biotin in E. coli
Authors: Delli-Bovi Teegan A , Spalding Maroya D , Prigge Sean T
Published: October 2010

Background

Biotin is an essential enzyme cofactor that acts as a CO2 carrier in carboxylation and decarboxylation reactions. The E. coli genome encodes a biosynthetic pathway that produces biotin from pimeloyl-CoA in four enzymatic steps. The final step, insertion of sulfur into desthiobiotin to form biotin, is catalyzed by the biotin synthase, BioB. A dedicated biotin ligase (BirA) catalyzes the covalent attachment of biotin to biotin-dependent enzymes. Isotopic labeling has been a valuable tool for probing the details of the biosynthetic process and assaying the activity of biotin-dependent enzymes, however there is currently no established method for 35S labeling of biotin.

Results

In this study, we produced [35S]-biotin from Na35SO4 and desthiobiotin with a specific activity of 30.7 Ci/mmol, two orders of magnitude higher than previously published methods. The biotinylation domain (PfBCCP-79) from the Plasmodium falciparum acetyl-CoA carboxylase (ACC) was expressed in E. coli as a biotinylation substrate. We found that overexpression of the E. coli biotin synthase, BioB, and biotin ligase, BirA, increased PfBCCP-79 biotinylation 160-fold over basal levels. Biotinylated PfBCCP-79 was purified by affinity chromatography, and free biotin was liberated using acid hydrolysis. We verified that we had produced radiolabeled biologically active [D]-biotin that specifically labels biotinylated proteins through reuptake in E. coli.

Conclusions

The strategy described in our report provides a simple and effective method for the production of [35S]-biotin in E. coli based on affinity chromatography.
Curcumin supplementation could improve diabetes-induced endothelial dysfunction associated with decreased vascular superoxide production and PKC inhibition
Authors: Rungseesantivanon Sirada , Thenchaisri Naris , Ruangvejvorachai Preecha , Patumraj Suthiluk
Published: October 2010

Background

Curcumin, an Asian spice and food-coloring agent, is known for its anti-oxidant properties. We propose that curcumin can improve diabetes-induced endothelial dysfunction through superoxide reduction.

Methods

Diabetes (DM) was induced in rats by streptozotocin (STZ). Daily curcumin oral feeding was started six weeks after the STZ injection. Twelve weeks after STZ injection, mesenteric arteriolar responses were recorded in real time using intravital fluorescence videomicroscopy. Superoxide and vascular protein kinase C (PKC-βII) were examined by hydroethidine and immunofluorescence, respectively.

Results

The dilatory response to acetylcholine (ACh) significantly decreased in DM arterioles as compared to control arterioles. There was no difference among groups when sodium nitroprusside (SNP) was used. ACh responses were significantly improved by both low and high doses (30 and 300 mg/kg, respectively) of curcumin supplementation. An oxygen radical-sensitive fluorescent probe, hydroethidine, was used to detect intracellular superoxide anion (O2
●-) production. O2
●- production was markedly increased in DM arterioles, but it was significantly reduced by supplementation of either low or high doses of curcumin. In addition, with a high dose of curcumin, diabetes-induced vascular PKC-βII expression was diminished.

Conclusion

Therefore, it is suggested that curcumin supplementation could improve diabetes-induced endothelial dysfunction significantly in relation to its potential to decrease superoxide production and PKC inhibition.
Automated cleaning of fan coil units with a natural detergent-disinfectant product
Authors: Liguori Giorgio , Bagattini Maria , Gallè Francesca , Negrone Mario , Di Onofrio Valeria , Triassi Maria
Published: October 2010

Background

Air conditioning systems represent one important source of microbial pollutants for indoor air. In the past few years, numerous strategies have been conceived to reduce the contamination of air conditioners, mainly in hospital settings. The biocidal detergent BATT2 represents a natural product obtained through extraction from brown seaweeds, that has been tested previously on multidrug-resistant microorganisms.

Methods

BATT2 has been utilized for the disinfection of fan coil units from four air conditioning systems located in hospital environments with a mean degree of risk. Samples were collected from the air supplied by the conditioning systems and from the surfaces of fan coil units, before and after sanitization procedures. Total microbial counts at 37°C and 22°C and mycotic count at 32°C were evaluated. Staphylococci and Pseudomonas aeruginosa were also detected on surfaces samples.

Results

The biodetergent was able to reduce up 50% of the microbial pollution of fan coil units surfaces and air supplied by the air conditioners.

Conclusions

BATT2 could be considered for cleaning/disinfection of air conditioning systems, that should be performed on the basis of accurate and verifiable sanitization protocols.
Expression of the neuron-specific protein CHD5 is an independent marker of outcome in neuroblastoma
Authors: Garcia Idoia , Mayol Gemma , Rodríguez Eva , Suñol Mariona , Gershon Timothy R , Ríos José , Cheung Nai-Kong V , Kieran Mark W , George Rani E , Perez-Atayde Antonio R , Casala Carla , Galván Patricia , de Torres Carmen , Mora Jaume , Lavarino Cinzia
Published: October 2010

Background

The chromodomain, helicase DNA-binding protein 5 (CHD5) is a potential tumor suppressor gene located on chromosome 1p36, a region recurrently deleted in high risk neuroblastoma (NB). Previous data have shown thatCHD5mRNA is present in normal neural tissues and in low risk NB, nevertheless, the distribution of CHD5 protein has not been explored. The aim of this study was to investigate CHD5 protein expression as an immunohistochemical marker of outcome in NB. With this purpose, CHD5 protein expression was analyzed in normal neural tissues and neuroblastic tumors (NTs).CHD5gene and protein expression was reexamined after induction chemotherapy in a subset of high risk tumors to identify potential changes reflecting tumor response.

Results

We provide evidence that CHD5 is a neuron-specific protein, absent in glial cells, with diverse expression amongst neuron types. Within NTs, CHD5 immunoreactivity was found restricted to differentiating neuroblasts and ganglion-like cells, and absent in undifferentiated neuroblasts and stromal Schwann cells. Correlation between protein and mRNA levels was found, suggesting transcriptional regulation ofCHD5. An immunohistochemical analysis of 90 primary NTs highlighted a strong association of CHD5 expression with favorable prognostic variables (age at diagnosis <12 months, low clinical stage, and favorable histology; P < 0.001 for all), overall survival (OS) (P < 0.001) and event-free survival (EFS) (P < 0.001). Multivariate analysis showed that CHD5 prognostic value is independent of other clinical and biologically relevant parameters, and could therefore represent a marker of outcome in NB that can be tested by conventional immunohistochemistry. The prognostic value of CHD5 was confirmed in an independent, blinded set of 32 NB tumors (P < 0.001).

Reactivation ofCHD5expression after induction chemotherapy was observed mainly in those high risk tumors with induced tumor cell differentiation features. Remarkably, these NB tumors showed good clinical response and prolonged patient survival.

Conclusions

The neuron-specific protein CHD5 may represent a marker of outcome in NB that can be tested by conventional immunohistochemistry. Re-establishment of CHD5 expression induced by chemotherapy could be a surrogate marker of treatment response.
The efficacy of preoperative PET/CT for prediction of curability in surgery for locally advanced gastric carcinoma
Authors: Hur Hoon , Kim Sung Hoon , Kim Wook , Song Kyo Young , Park Cho Hyun , Jeon Hae Myung
Published: October 2010

Background

The benefits of preoperative 18FDG-PET/CT for gastric cancer remain uncertain. The aim of this study was to investigate the effects of preoperative 18FDG-PET/CT on the surgical strategy for locally advanced gastric cancer retrospectively.

Methods

From January 2007 to November 2008, 18FDG-PET/CT was performed in 142 patients who had been diagnosed with advanced gastric cancer by computed tomography or gastrofiberscope findings.

Results

Detection rates were 88.7% (126/142) for primary tumors and 24.6% (35/142) for local lymph nodes (LN). Nine patients with metastatic lesions underwent induction chemotherapy without operation. Of 133 patients subjected to operation, positive FDG uptake in primary tumors (p = 0.047) and local lymph nodes (p < 0.001) was related to non-curable operations. The mean standard uptake value (SUV) of primary tumors of patients who underwent non-curable operations was significantly higher than that of patients with curable operations (p = 0.001). When the SUV was greater than 5 and FDG uptake of LN was positive, non-curable operations were predicted with a sensitivity of 35.2%, a specificity of 91.0% and an accuracy of 76.7%.

Conclusions

High SUV of the primary tumor and positive FDG uptake in local lymph nodes at PET/CT could predict non-curative resection in locally advanced gastric cancer. Therefore, information from preoperative PET/CT can help physician decisions regarding other modalities without laparotomy.
Association between intratumoral lymphatic microvessel density (LMVD) and clinicopathologic features in endometrial cancer: a retrospective cohort study
Authors: Kawamura Lecy , Carvalho Filomena M , Alves Bernardo GL , Bacchi Carlos E , Goes Joao Carlos Sampaio , Calil Marcelo Alvarenga , Baracat Edmund C , Carvalho Jesus P
Published: October 2010

Background

Lymph node metastasis in endometrial cancer significantly decreases survival rate. Few data on the influence of intratumoral lymphatic microvessel density (LMVD) on survival in endometrial cancer are available. Our aim was to assess the intratumoral LMVD of endometrial carcinomas and to investigate its association with classical pathological factors, lymph node metastasis and survival.

Methods

Fifty-seven patients with endometrial carcinoma diagnosed between 2000 and 2008 underwent complete surgical staging and evaluation of intratumoral LMVD and other histologic variables. Lymphatic microvessels were identified by immunohistochemical staining using monoclonal antibody against human podoplanin (clone D2-40) and evaluated by counting the number of immunostained lymphatic vessels in 10 hot spot areas at 400× magnification. The LMVD was expressed by the mean number of vessels in these 10 hot spot microscopic fields. We next investigated the association of LMVD with the clinicopathologic findings and prognosis.

Results

The mean number of lymphatic vessels counted in all cases ranged between 0 and 4.7. The median value of mean LMVD was 0.5, and defined the cut-off for low and high LMVD. We identified low intratumoral LMVD in 27 (47.4%) patients and high LMVD in 30 (52.6%) patients. High intratumoral LMVD was associated with lesser miometrial and adnaexal infiltration, lesser cervical and peritoneal involvement, and fewer fatal cases. Although there was lower lymph node involvement among cases with high LMVD, the difference did not reach significance. No association was seen between LMVD and FIGO staging, histological type, or vascular invasion. On the other hand, low intratumoral LMVD was associated with poor outcome. Seventy-five percent of deaths occurred in patients with low intratumoral LMVD.

Conclusion

Our results show association of high intratumoral LMVD with features related to more localized disease and better outcome. We discuss the role of lymphangiogenesis as an early event in the endometrial carcinogenesis.
Assessment of the quality and variability of health information on chronic pain websites using the DISCERN instrument
Authors: Kaicker Jatin , Borg Debono Victoria , Dang Wilfred , Buckley Norman , Thabane Lehana
Published: October 2010

Background

The Internet is used increasingly by providers as a tool for disseminating pain-related health information and by patients as a resource about health conditions and treatment options. However, health information on the Internet remains unregulated and varies in quality, accuracy and readability. The objective of this study was to determine the quality of pain websites, and explain variability in quality and readability between pain websites.

Methods

Five key terms (pain, chronic pain, back pain, arthritis, and fibromyalgia) were entered into the Google, Yahoo and MSN search engines. Websites were assessed using the DISCERN instrument as a quality index. Grade level readability ratings were assessed using the Flesch-Kincaid Readability Algorithm. Univariate (using alpha = 0.20) and multivariable regression (using alpha = 0.05) analyses were used to explain the variability in DISCERN scores and grade level readability using potential for commercial gain, health related seals of approval, language(s) and multimedia features as independent variables.

Results

A total of 300 websites were assessed, 21 excluded in accordance with the exclusion criteria and 110 duplicate websites, leaving 161 unique sites. About 6.8% (11/161 websites) of the websites offered patients' commercial products for their pain condition, 36.0% (58/161 websites) had a health related seal of approval, 75.8% (122/161 websites) presented information in English only and 40.4% (65/161 websites) offered an interactive multimedia experience. In assessing the quality of the unique websites, of a maximum score of 80, the overall average DISCERN Score was 55.9 (13.6) and readability (grade level) of 10.9 (3.9). The multivariable regressions demonstrated that website seals of approval (P = 0.015) and potential for commercial gain (P = 0.189) were contributing factors to higher DISCERN scores, while seals of approval (P = 0.168) and interactive multimedia (P = 0.244) contributed to lower grade level readability, as indicated by estimates of the beta coefficients.

Conclusion

The overall quality of pain websites is moderate, with some shortcomings. Websites that scored high using the DISCERN questionnaire contained health related seals of approval and provided commercial solutions for pain related conditions while those with low readability levels offered interactive multimedia options and have been endorsed by health seals.
TGFβ signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke
Authors: Doyle Kristian P , Cekanaviciute Egle , Mamer Lauren E , Buckwalter Marion S
Published: October 2010

Background

TGFβ is both neuroprotective and a key immune system modulator and is likely to be an important target for future stroke therapy. The precise function of increased TGF-β1 after stroke is unknown and its pleiotropic nature means that it may convey a neuroprotective signal, orchestrate glial scarring or function as an important immune system regulator. We therefore investigated the time course and cell-specificity of TGFβ signaling after stroke, and whether its signaling pattern is altered by gender and aging.

Methods

We performed distal middle cerebral artery occlusion strokes on 5 and 18 month old TGFβ reporter mice to get a readout of TGFβ responses after stroke in real time. To determine which cell type is the source of increased TGFβ production after stroke, brain sections were stained with an anti-TGFβ antibody, colocalized with markers for reactive astrocytes, neurons, and activated microglia. To determine which cells are responding to TGFβ after stroke, brain sections were double-labelled with anti-pSmad2, a marker of TGFβ signaling, and markers of neurons, oligodendrocytes, endothelial cells, astrocytes and microglia.

Results

TGFβ signaling increased 2 fold after stroke, beginning on day 1 and peaking on day 7. This pattern of increase was preserved in old animals and absolute TGFβ signaling in the brain increased with age. Activated microglia and macrophages were the predominant source of increased TGFβ after stroke and astrocytes and activated microglia and macrophages demonstrated dramatic upregulation of TGFβ signaling after stroke. TGFβ signaling in neurons and oligodendrocytes did not undergo marked changes.

Conclusions

We found that TGFβ signaling increases with age and that astrocytes and activated microglia and macrophages are the main cell types that undergo increased TGFβ signaling in response to post-stroke increases in TGFβ. Therefore increased TGFβ after stroke likely regulates glial scar formation and the immune response to stroke.
Molecular signature of response and potential pathways related to resistance to the HSP90 inhibitor, 17AAG, in breast cancer
Authors: Zajac Magdalena , Gomez Gonzalo , Benitez Javier , Martínez-Delgado Beatriz
Published: October 2010

Background

HSP90 may be a favorable target for investigational therapy in breast cancer. In fact, the HSP90 inhibitor, 17AAG, currently has entered in phase II clinical trials as an anticancer agent in breast and other tumors. Since HSP90 inhibition leads to global depletion of oncogenic proteins involved in multiple pathways we applied global analysis using gene array technology to study new genes and pathways involved in the drug response in breast cancer.

Methods

Gene expression profiling using Whole Human Genome Agilent array technology was applied to a total of six sensitive and two resistant breast cancer cell lines pre-treatment and treated with the 17AAG for 24 and 48 hours.

Results

We have identified a common molecular signature of response to 17AAG composed of 35 genes which include novel pharmacodynamic markers of this drug. In addition, different patterns of HSP90 client transcriptional changes after 17AAG were identified associated to the sensitive cell lines, which could be useful to evaluate drug effectiveness. Finally, we have found differentially expressed pathways associated to resistance to 17AAG. We observed significant activation of NF-κB and MAPK pathways in resistant cells upon treatment, indicating that these pathways could be potentially targeted to overcome resistance.

Conclusions

Our study shows that global mRNA expression analysis is a useful strategy to examine molecular effects of drugs, which allowed us the discovery of new biomarkers of 17AAG activity and provided more insights into the complex mechanism of 17AAG resistance.
Lipoprotein biosynthesis as a target for anti-Wolbachia treatment of filarial nematodes
Authors: Johnston Kelly L , Wu Bo , Guimarães Ana , Ford Louise , Slatko Barton E , Taylor Mark J
Published: October 2010

Background

Lymphatic filariasis and onchocerciasis are debilitating diseases caused by filarial nematodes. Disease pathogenesis is induced by inflammatory responses following the death of the parasite. Wolbachia endosymbionts of filariae are potent inducers of innate and adaptive inflammation and bacterial lipoproteins have been identified as the ligands that bind toll-like receptors (TLR) 2 and TLR6. Lipoproteins are important structural and functional components of bacteria and therefore enzymes involved in Wolbachia lipoprotein biosynthesis are potential chemotherapeutic targets.

Results

Globomycin, a signal peptidase II (LspA) inhibitor, has activity against Gram-negative bacteria and a putative lspA gene has been identified from the Wolbachia genome of Brugia malayi (w Bm). The amino acids required for function are strictly conserved and functionality was verified by complementation tests in a temperature-sensitive Escherichia coli lspA mutant. Also, transformation of wild type E. coli with Wolbachia lspA conferred significant globomycin resistance. A cell-based screen has been developed utilizing a Wolbachia-containing Aedes albopictus cell line to assay novel compounds active against Wolbachia. Globomycin was screened using this assay, which resulted in a dose-dependent reduction in Wolbachia load. Furthermore, globomycin was also effective in reducing the motility and viability of adult B. malayi in vitro.

Conclusions

These studies validate lipoprotein biosynthesis as a target in an organism for which no genetic tools are available. Further studies to evaluate drugs targeting this pathway are underway as part of the A-WOL drug discovery and development program.
The candidate tumor suppressor gene ECRG4 inhibits cancer cells migration and invasion in esophageal carcinoma
Authors: Li Linwei , Zhang Chunpeng , Li Xiaoyan , Lu ShihHsin , Zhou Yun
Published: October 2010

Background

The esophageal cancer related gene 4 (ECRG4) was initially identified and cloned in our laboratory from human normal esophageal epithelium (GenBank accession no.AF325503). ECRG4 was a new tumor suppressor gene in esophageal squamous cell carcinoma (ESCC) associated with prognosis. In this study, we investigated the novel tumor-suppressing function of ECRG4 in cancer cell migration, invasion, adhesion and cell cycle regulation in ESCC.

Methods

Transwell and Boyden chamber experiments were utilized to examined the effects of ECRG4 expression on ESCC cells migration, invasion and adhesion. And flow cytometric analysis was used to observe the impact of ECRG4 expression on cell cycle regulation. Finally, the expression levels of cell cycle regulating proteins p53 and p21 in human ESCC cells transfected with ECRG4 gene were evaluated by Western blotting.

Results

The restoration of ECRG4 expression in ESCC cells inhibited cancer cells migration and invasion (P < 0.05), which did not affect cell adhesion capacity (P > 0.05). Furthermore, ECRG4 could cause cell cycle G1 phase arrest in ESCC (P < 0.05), through inducing the increased expression of p53 and p21 proteins.

Conclusion

ECRG4 is a candidate tumor suppressor gene which suppressed tumor cells migration and invasion without affecting cell adhesion ability in ESCC. Furthermore, ECRG4 might cause cell cycle G1 phase block possibly through inducing the increased expression of p53 and p21 proteins in ESCC.
Ex-vivo expanded human NK cells express activating receptors that mediate cytotoxicity of allogeneic and autologous cancer cell lines by direct recognition and antibody directed cellular cytotoxicity
Authors: Voskens Caroline J , Watanabe Ryuko , Rollins Sandra , Campana Dario , Hasumi Kenichiro , Mann Dean L
Published: October 2010

Background

The possibility that autologous NK cells could serve as an effective treatment modality for solid tumors has long been considered. However, implementation is hampered by (i) the small number of NK cells in peripheral blood, (ii) the difficulties associated with large-scale production of GMP compliant cytolytic NK cells, (iii) the need to activate the NK cells in order to induce NK cell mediated killing and (iv) the constraints imposed by autologous inhibitory receptor-ligand interactions. To address these issues, we determined (i) if large numbers of NK cells could be expanded from PBMC and GMP compliant cell fractions derived by elutriation, (ii) their ability to kill allogeneic and autologous tumor targets by direct cytotoxitiy and by antibody-mediated cellular cytotoxicity and (iii) defined NK cell specific receptor-ligand interactions that mediate tumor target cell killing.

Methods

Human NK cells were expanded during 14 days. Expansion efficiency, NK receptor repertoire before and after expansion, expression of NK specific ligands, cytolytic activity against allogeneic and autologous tumor targets, with and without the addition of chimeric EGFR monoclonal antibody, were investigated.

Results

Cell expansion shifted the NK cell receptor repertoire towards activation and resulted in cytotoxicity against various allogeneic tumor cell lines and autologous gastric cancer cells, while sparing normal PBMC. Blocking studies confirmed that autologous cytotoxicity is established through multiple activating receptor-ligand interactions. Importantly, expanded NK cells also mediated ADCC in an autologous and allogeneic setting by antibodies that are currently being used to treat patients with select solid tumors.

Conclusion

These data demonstrate that large numbers of cytolytic NK cells can be generated from PBMC and lymphocyte-enriched fractions obtained by GMP compliant counter current elutriation from PBMC, establishing the preclinical evidence necessary to support clinical trials utilizing autologous expanded NK cells, both directly and in combination with monoclonal antibodies in future cell-based immunotherapy in select solid tumors.
A multigene predictor of metastatic outcome in early stage hormone receptor-negative and triple-negative breast cancer
Authors: Yau Christina , Esserman Laura , Moore Dan H , Waldman Fred , Sninsky John , Benz Christopher C
Published: October 2010

Introduction

Various multigene predictors of breast cancer clinical outcome have been commercialized, but proved to be prognostic only for hormone receptor (HR) subsets overexpressing estrogen or progesterone receptors. Hormone receptor negative (HRneg) breast cancers, particularly those lacking HER2/ErbB2 overexpression and known as triple-negative (Tneg) cases, are heterogeneous and generally aggressive breast cancer subsets in need of prognostic subclassification, since most early stage HRneg and Tneg breast cancer patients are cured with conservative treatment yet invariably receive aggressive adjuvant chemotherapy.

Methods

An unbiased search for genes predictive of distant metastatic relapse was undertaken using a training cohort of 199 node-negative, adjuvant treatment naïve HRneg (including 154 Tneg) breast cancer cases curated from three public microarray datasets. Prognostic gene candidates were subsequently validated using a different cohort of 75 node-negative, adjuvant naïve HRneg cases curated from three additional datasets. The HRneg/Tneg gene signature was prognostically compared with eight other previously reported gene signatures, and evaluated for cancer network associations by two commercial pathway analysis programs.

Results

A novel set of 14 prognostic gene candidates was identified as outcome predictors: CXCL13, CLIC5, RGS4, RPS28, RFX7, EXOC7, HAPLN1, ZNF3, SSX3, HRBL, PRRG3, ABO, PRTN3, MATN1. A composite HRneg/Tneg gene signature index proved more accurate than any individual candidate gene or other reported multigene predictors in identifying cases likely to remain free of metastatic relapse. Significant positive correlations between the HRneg/Tneg index and three independent immune-related signatures (STAT1, IFN, and IR) were observed, as were consistent negative associations between the three immune-related signatures and five other proliferation module-containing signatures (MS-14, ONCO-RS, GGI, CSR/wound and NKI-70). Network analysis identified 8 genes within the HRneg/Tneg signature as being functionally linked to immune/inflammatory chemokine regulation.

Conclusions

A multigene HRneg/Tneg signature linked to immune/inflammatory cytokine regulation was identified from pooled expression microarray data and shown to be superior to other reported gene signatures in predicting the metastatic outcome of early stage and conservatively managed HRneg and Tneg breast cancer. Further validation of this prognostic signature may lead to new therapeutic insights and spare many newly diagnosed breast cancer patients the need for aggressive adjuvant chemotherapy.
Clinical correlates of arterial lactate levels in patients with ST-segment elevation myocardial infarction at admission: a descriptive study
Authors: Vermeulen Robert P , Hoekstra Miriam , Nijsten Maarten WN , van der Horst Iwan C , van Pelt L Joost , Jessurun Gillian A , Jaarsma Tiny , Zijlstra Felix , van den Heuvel Ad F
Published: October 2010

Introduction

Blood lactate measurements can be used as an indicator of hemodynamic impairment and relate to mortality in various forms of shock. Little is known at the moment concerning the clinical correlates of systemic lactate in patients with ST-segment elevation myocardial infarction (STEMI).

Methods

To assess the relation of systemic arterial lactate levels in STEMI patients with clinical correlates at presentation in the catheterization laboratory, we measured arterial lactate levels with a rapid point-of-care technique, immediately following femoral sheath insertion. The study population (n= 1,176) was divided into tertiles with lactate levels ≤1.1 (n = 410), 1.2 to 1.7 (n = 398) and ≥1.8 mmol/l (n = 368). We compared both baseline characteristics and outcome measures of the three lactate groups.

Results

Factors independently associated with higher lactate levels were hypotension, heart rate, thrombolysis in myocardial infarction (TIMI) flow 0 to 1, diabetes and non-smoking. Mortality at 30 days in the three groups was 2.0%, 1.5% and 6.5%. The latter group also showed lower blush grades and greater enzymatic infarct sizes. An intra aortic balloon pump (IABP) was used more frequently in patients with higher lactate levels (4.2%, 7.6% and 14.7%).

Conclusions

In STEMI patients, impaired hemodynamics, worse TIMI flow and non-smoking were related to increased arterial lactate levels. Higher lactate levels were independently related with 30-day mortality and an overall worse response to percutaneous coronary intervention (PCI). In particular, acute mortality was related to admission lactates ≥1.8 mmol/L. Point-of-care measurement of arterial lactate at admission in patients with STEMI has the potential to improve acute risk stratification.
Nebulized heparin is associated with fewer days of mechanical ventilation in critically ill patients: a randomized controlled trial
Authors: Dixon Barry , Schultz Marcus J , Smith Roger , Fink James B , Santamaria John D , Campbell Duncan J
Published: October 2010

Introduction

Prolonged mechanical ventilation has the potential to aggravate or initiate pulmonary inflammation and cause lung damage through fibrin deposition. Heparin may reduce pulmonary inflammation and fibrin deposition. We therefore assessed whether nebulized heparin improved lung function in patients expected to require prolonged mechanical ventilation.

Methods

Fifty patients expected to require mechanical ventilation for more than 48 hours were enrolled in a double-blind randomized placebo-controlled trial of nebulized heparin (25,000 U) or placebo (normal saline) 4 or 6 hourly, depending on patient height. The study drug was continued while the patient remained ventilated to a maximum of 14 days from randomization.

Results

Nebulized heparin was not associated with a significant improvement in the primary end-point, the average daily partial pressure of oxygen to inspired fraction of oxygen ratio while mechanically ventilated, but was associated with improvement in the secondary end-point, ventilator-free days amongst survivors at day 28 (22.6 ± 4.0 versus 18.0 ± 7.1, treatment difference 4.6 days, 95% CI 0.9 to 8.3, P = 0.02). Heparin administration was not associated with any increase in adverse events.

Conclusions

Nebulized heparin was associated with fewer days of mechanical ventilation in critically ill patients expected to require prolonged mechanical ventilation. Further trials are required to confirm these findings.

Trial registration

The Australian Clinical Trials Registry (ACTR-12608000121369).
Open lung approach associated with high-frequency oscillatory or low tidal volume mechanical ventilation improves respiratory function and minimizes lung injury in healthy and injured rats
Authors: Krebs Joerg , Pelosi Paolo , Tsagogiorgas Charalambos , Zoeller Liesa , Rocco Patricia RM , Yard Benito , Luecke Thomas
Published: October 2010

Introduction

To test the hypothesis that open lung (OL) ventilatory strategies using high-frequency oscillatory ventilation (HFOV) or controlled mechanical ventilation (CMV) compared to CMV with lower positive end-expiratory pressure (PEEP) improve respiratory function while minimizing lung injury as well as systemic inflammation, a prospective randomized study was performed at a university animal laboratory using three different lung conditions.

Methods

Seventy-eight adult male Wistar rats were randomly assigned to three groups: (1) uninjured (UI), (2) saline washout (SW), and (3) intraperitoneal/intravenous Escherichia coli lipopolysaccharide (LPS)-induced lung injury. Within each group, animals were further randomized to (1) OL with HFOV, (2) OL with CMV with "best" PEEP set according to the minimal static elastance of the respiratory system (BP-CMV), and (3) CMV with low PEEP (LP-CMV). They were then ventilated for 6 hours. HFOV was set with mean airway pressure (PmeanHFOV) at 2 cm H2O above the mean airway pressure recorded at BP-CMV (PmeanBP-CMV) following a recruitment manoeuvre. Six animals served as unventilated controls (C). Gas-exchange, respiratory system mechanics, lung histology, plasma cytokines, as well as cytokines and types I and III procollagen (PCI and PCIII) mRNA expression in lung tissue were measured.

Results

We found that (1) in both SW and LPS, HFOV and BP-CMV improved gas exchange and mechanics with lower lung injury compared to LP-CMV, (2) in SW; HFOV yielded better oxygenation than BP-CMV; (3) in SW, interleukin (IL)-6 mRNA expression was lower during BP-CMV and HFOV compared to LP-CMV, while in LPS inflammatory response was independent of the ventilatory mode; and (4) PCIII mRNA expression decreased in all groups and ventilatory modes, with the decrease being highest in LPS.

Conclusions

Open lung ventilatory strategies associated with HFOV or BP-CMV improved respiratory function and minimized lung injury compared to LP-CMV. Therefore, HFOV with PmeanHFOV set 2 cm H2O above the PmeanBP-CMV following a recruitment manoeuvre is as beneficial as BP-CMV.
“Retribution Will Be Their Reward”: New Mexico's Las Gorras Blancas and the Fight for the Las Vegas Land Grant Commons
Authors: Correia David
Published: October 2010

This essay traces the struggle for the commons on New Mexico's Las Vegas Land Grant, a community property claim in New Mexico. Following the U.S.–Mexican War, waves of enclosures undermined communal property relations throughout the region. The Las Vegas grant was particularly appealing to land speculators and commercial cattle operators for its vast grasslands, timber, and rail connections. In the late 1880s a clandestine movement, known as Las Gorras Blancas, responded to the property enclosures and new wage labor relations on the grant with night-riding tactics that included cutting the barbed wire fences that enclosed common property and destroying the rail infrastructure that served the new class of speculators and commercial cattle operators. This essay examines the specific patterns of land speculation in Las Vegas amid the wider capitalist transformation of New Mexico as a means to understand the development and political economy of the Las Gorras Blancas protest.
Enclosures from the Bottom Up
Authors: Linebaugh Peter
Published: October 2010

This essay integrates two themes: the enclosure of land, or of other resources, as a physical mechanism of privatization; and the technique of historical investigation known as writing history “from the bottom up.” Building on the work of Elinor Ostrom, the 2009 Nobel laureate in economics for her work on the commons, the essay criticizes the powerful and influential 1968 article “The Tragedy of the Commons” by the biologist Garrett Hardin. It demonstrates how Hardin's central argument is derived from the ideas of a nineteenth-century Oxford professor responding to a protracted series of militant actions by a small community in Oxfordshire that sought to defend its commons from enclosure. The acts of resistance exerted by these Oxfordshire commoners were among the first events uncovered and written about by members of the Ruskin College History Workshop who pioneered history “from below” in England during the early 1970s.
Ex-Communicated: Historical Reflections on Enclosure Landscapes in Palestine
Authors: Fields Gary
Published: October 2010

“Ex-Communicated” tells a story about enclosure on the Palestinian landscape through photographic images that reference themes from the enclosures in early modern England and highlight the historically long-standing interplay of power and space. Using Michel Foucault's spatial notion of power as a theoretical anchor, and the enclosures in England as a historical foundation, the article shows how dominant groups with territorial ambitions enclose and remake landscapes by means of legal changes in property relations and by material changes in landscape architecture. These two instruments enable dominant groups to recast systems of land ownership, occupancy, and use and reconfigure routes of circulation and trespass on the landscape with the aim of forcing subaltern populations into ever smaller territorial spaces and of taking control of the landscape. The Palestinian landscape is part of this historically recurrent pattern of power and enclosure on the land.
Puritanism, (Monarchical) Republicanism, and Monarchy; or John Whitgift, Antipuritanism, and the “Invention” of Popularity
Authors: Lake Peter
Published: October 2010

There has been much talk of late about the Elizabethan state as a “monarchical republic” and about the emergence in and through the religious disputes of Elizabethan England of a “post-Reformation public sphere.” The term popularity emerged as a pejorative term used by contemporaries to refer to and condemn the sorts of attitudes and modes of communicative and political action associated in the recent scholarship with those terms. This essay traces the emergence of popularity as both a term of abuse and as something of an analytic category in the antipuritan and more particularly the antipresbyterian polemic of the 1570s. The argument is that John Whitgift's conduct of that polemic represents a crucial moment in the process whereby the term popularity gained much of its immediate (and subsequent) purchase and power, and that in this context of antipuritan polemic the theory of popularity as a bad thing was first coherently developed and adumbrated by contemporaries. The essay also makes a case for religious and particularly eccesiological dispute as an under-used source for the ways in which contemporaries thought about politics.
Transforming Work: Protestantism and the Piers Plowman Tradition
Authors: Little Katherine C.
Published: October 2010

The figure of the plowman achieved a certain popularity in mid-sixteenth-century England with the publication of William Langland's medieval poem, Piers Plowman, and in a number of treatises written in imitation of it such as I playne Piers which cannot flatter. This post-Reformation plowman has long been read as an uncomplicated spokesman for an anticlerical Protestantism. This article argues, in contrast, that these plowmen are evidence of a continuing interest in a medieval Catholic symbolic imagination centered on work–as physical labor and as spiritual labor, such as good deeds. In other words, the new Protestant deemphasis on spiritual works was understood at the time to threaten the reformist and even radical potential of discourses of rural labor. This popular figure of the plowman demonstrates, therefore, the conflict between residual and emergent meanings of labor.
Evolutionary crossroads in developmental biology: Physcomitrella patens
Authors: Prigge Michael J. , Bezanilla Magdalena
Published: October 2010

The moss Physcomitrella patens has recently emerged as a powerful genetically tractable model plant system. As a member of the bryophytes, P. patens provides a unique opportunity to study the evolution of a myriad of plant traits, such as polarized cell growth, gametophyte-to-sporophyte transitions, and sperm-to-pollen transition. The availability of a complete genome sequence, together with the ability to perform gene targeting efficiently in P. patens has spurred a flurry of elegant reverse genetic studies in this plant model that address a variety of key questions in plant developmental biology.
Expression and function of the empty spiracles gene in olfactory sense organ development of Drosophila melanogaster
Authors: Sen Sonia , Hartmann Beate , Reichert Heinrich , Rodrigues Veronica
Published: October 2010

In Drosophila, the cephalic gap gene empty spiracles plays key roles in embryonic patterning of the peripheral and central nervous system. During postembryonic development, it is involved in the development of central olfactory circuitry in the antennal lobe of the adult. However, its possible role in the postembryonic development of peripheral olfactory sense organs has not been investigated. Here, we show that empty spiracles acts in a subset of precursors that generate the olfactory sense organs of the adult antenna. All empty spiracles-expressing precursor cells co-express the proneural gene amos and the early patterning gene lozenge. Moreover, the expression of empty spiracles in these precursor cells is dependent on both amos and lozenge. Functional analysis reveals two distinct roles of empty spiracles in the development of olfactory sense organs. Genetic interaction studies in a lozenge-sensitized background uncover a requirement of empty spiracles in the formation of trichoid and basiconic olfactory sensilla. MARCM-based clonal mutant analysis reveals an additional role during axonal targeting of olfactory sensory neurons to glomeruli within the antennal lobe. Our findings on empty spiracles action in olfactory sense organ development complement previous studies that demonstrate its requirement in olfactory interneurons and, taken together with studies on the murine homologs of empty spiracles, suggest that conserved molecular genetic programs might be responsible for the formation of both peripheral and central olfactory circuitry in insects and mammals.
Olfactory modulation of flight in Drosophila is sensitive, selective and rapid
Authors: Bhandawat Vikas , Maimon Gaby , Dickinson Michael H. , Wilson Rachel I.
Published: October 2010

Freely flying Drosophila melanogaster respond to odors by increasing their flight speed and turning upwind. Both these flight behaviors can be recapitulated in a tethered fly, which permits the odor stimulus to be precisely controlled. In this study, we investigated the relationship between these behaviors and odor-evoked activity in primary sensory neurons. First, we verified that these behaviors are abolished by mutations that silence olfactory receptor neurons (ORNs). We also found that antennal mechanosensors in Johnston's organ are required to guide upwind turns. Flight responses to an odor depend on the identity of the ORNs that are active, meaning that these behaviors involve odor discrimination and not just odor detection. Flight modulation can begin rapidly (within about 85 ms) after the onset of olfactory transduction. Moreover, just a handful of spikes in a single ORN type is sufficient to trigger these behaviors. Finally, we found that the upwind turn is triggered independently from the increase in wingbeat frequency, implying that ORN signals diverge to activate two independent and parallel motor commands. Together, our results show that odor-evoked flight modulations are rapid and sensitive responses to specific patterns of sensory neuron activity. This makes these behaviors a useful paradigm for studying the relationship between sensory neuron activity and behavioral decision-making in a simple and genetically tractable organism.
The role of serotonin in the enhancement of long-term memory resulting from predator detection in Lymnaea
Authors: Il-Han Jae , Janes Tara , Lukowiak Ken
Published: October 2010

Serotonergic systems play important roles in modulating stress-induced arousal and vigilance behaviours. The pond snail, Lymnaea, shows multiple defensive vigilance behaviours in response to the stress associated with predator detection. Predator detection elicited by crayfish effluent (CE), increases the time to re-emerge from the shell and enhances the shadow withdrawal response. More importantly, in Lymnaea, CE enhances the ability to form long-term memory (LTM). We investigated the role of the serotonergic system in these anti-predator responses in Lymnaea. Using a serotonin-receptor antagonist, mianserin, we found that two defensive vigilance behaviours (e.g. increasing the time to re-emerge from their shell and shadow response) elicited by CE were not observed when the serotonergic system was disrupted. Also, methysergide, another serotonin antagonist, blocked the enhanced LTM formation after training in CE. Importantly, mianserin did not alter LTM formation in pond water (PW). These data suggest that a serotonergic system is activated only when Lymnaea detect a predator. When snails were trained in CE using a training procedure that in PW produces a 24-h LTM, a more persistent form of LTM (5 days) occurred. This more persistent form of LTM was abolished after mianserin treatment. Increasing 5-HT levels in the snail by the injection of 5-HT was also associated with enhanced LTM formation. Lastly, we tested whether the osphradium is implicated in CE detection and subsequent enhanced formation of LTM. Cutting the osphradial nerve to the CNS resulted in the loss of the ability to form enhanced LTM in CE. Together, these findings support the hypothesis that the serotonergic system plays a key role in modulating the predator-induced stress responses in Lymnaea.
Sound detection by the longfin squid (Loligo pealeii) studied with auditory evoked potentials: sensitivity to low-frequency particle motion and not pressure
Authors: Mooney T. Aran , Hanlon Roger T. , Christensen-Dalsgaard Jakob , Madsen Peter T. , Ketten Darlene R. , Nachtigall Paul E.
Published: October 2010

Although hearing has been described for many underwater species, there is much debate regarding if and how cephalopods detect sound. Here we quantify the acoustic sensitivity of the longfin squid (Loligo pealeii) using near-field acoustic and shaker-generated acceleration stimuli. Sound field pressure and particle motion components were measured from 30 to 10,000 Hz and acceleration stimuli were measured from 20 to 1000 Hz. Responses were determined using auditory evoked potentials (AEPs) with electrodes placed near the statocysts. Evoked potentials were generated by both stimuli and consisted of two wave types: (1) rapid stimulus-following waves, and (2) slower, high-amplitude waves, similar to some fish AEPs. Responses were obtained between 30 and 500 Hz with lowest thresholds between 100 and 200 Hz. At the best frequencies, AEP amplitudes were often >20 μV. Evoked potentials were extinguished at all frequencies if (1) water temperatures were less than 8°C, (2) statocysts were ablated, or (3) recording electrodes were placed in locations other than near the statocysts. Both the AEP response characteristics and the range of responses suggest that squid detect sound similarly to most fish, with the statocyst acting as an accelerometer through which squid detect the particle motion component of a sound field. The modality and frequency range indicate that squid probably detect acoustic particle motion stimuli from both predators and prey as well as low-frequency environmental sound signatures that may aid navigation.
Factor Immobility and Regional Impacts of Trade Liberalization: Evidence on Poverty from India
Authors: Topalova Petia
Published: October 2010

This paper uses the 1991 Indian trade liberalization to measure the impact of trade liberalization on poverty, and to examine the mechanisms underpinning this impact. Variation in sectoral composition across districts and liberalization intensity across production sectors allows a difference-in-difference approach. Rural districts, in which production sectors more exposed to liberalization were concentrated, experienced slower decline in poverty and lower consumption growth. The impact of liberalization was most pronounced among the least geographically mobile at the bottom of the income distribution, and in Indian states where inflexible labor laws impeded factor reallocation across sectors. (JEL F13, I32, O15, O18, O19, O24)