bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain‐derived neurotrophic factor induces proliferation of human airway smooth muscle cells
Authors: Aravamudan Bharathi , Thompson Michael , Pabelick Christina , Prakash Y. S. 
Published: June 2011

AbstractAirway diseases such as asthma involve increased airway smooth muscle (ASM) contractility and remodelling via enhanced proliferation. Neurotrophins (NTs) such as brain‐derived neurotrophic factor (BDNF), well‐known in the nervous system, can regulate Ca2+ signalling, and interact with cytokines in contributing to airway hyperreactivity. In this study, we determined whether and how BDNF regulates human ASM cell proliferation in the presence of inflammation, thus testing its potential role in airway remodelling. Cells were treated with 10 nM BDNF, 25 ng/ml tumour necrosis factor (TNF‐α) or interleukin‐13 (IL‐13), or 10 ng/ml platelet‐derived growth factor (PDGF). Proliferation was measured using CyQuant dye, with immunoblotting of cell cycle proteins predicted to change with proliferation. Forty‐eight hours of BDNF enhanced ASM proliferation to ∼50% of that by PDGF or cytokines. Transfection with small interfering RNAs (siRNAs) targeting high‐affinity tropomyosin‐related kinase B receptor abolished BDNF effects on proliferation, whereas low‐affinity 75 kD neurotrophin receptor (p75NTR) siRNA had no effect. Systematic pharmacologic inhibition of different components of ERK1/2 and PI3K/Akt1 pathways blunted BDNF or TNF‐α–induced proliferation. BDNF also induced IκB phosphorylation and nuclear translocation of p50 and p65 NF‐κB subunits, with electron mobility shift assay confirmation of NF‐κB binding to consensus DNA sequence. These results demonstrate that NTs such as BDNF can enhance human ASM cell proliferation by activating proliferation‐specific signalling pathways and a versatile transcription factor such as NF‐κB, which are common to cytokines and growth factors involved in asthma.
Pregnancy worries: a longitudinal study of Spanish women
Authors: PEÑACOBA‐PUENTE CECILIA , MONGE FRANCISCO JAVIER CARMONA , MORALES DOLORES MARÍN 
Published: June 2011

AbstractObjective. To identify pregnancy worries in women by assessing the intensity of these worries and how they change over the course of pregnancy, as well as their relations with sociodemographic and clinical variables. Design. Longitudinal study using a postal questionnaire. Setting. University hospital in Madrid. Population. 285 pregnant women. Method. Women were asked about their pregnancy‐specific worries in their first trimester (mean gestational age 14.4 weeks) and third trimester (mean gestational age 34.3 weeks). Main Outcome Measures. The women completed a questionnaire that included sociodemographic information and the Cambridge Worry Scale. Results. Pregnancy worries were significantly reduced during the third trimester. The main concern throughout gestation was worry about fetal health. Multiparity and pregnancy planning protected women from pregnancy worries, whereas having had a miscarriage had a negative effect. A younger age and being employed contributed to greater socioeconomic worries. Conclusions. Worries related to the health of the fetus are universal across different nationalities. A first pregnancy, unplanned pregnancy, and previous miscarriage are risk factors that influence the intensity of a woman's worries. To improve the health and quality of life of pregnant women, a holistic approach to their care should include evaluation of their worries and appropriate intervention in particular groups considered at risk.
Algal biochar: effects and applications
Authors: BIRD MICHAEL I. , WURSTER CHRISTOPHER M. , DE PAULA SILVA PEDRO H. , PAUL NICHOLAS A. , DE NYS ROCKY 
Published: June 2011

AbstractAlgae represent a promising target for the generation of bioenergy through slow pyrolysis, leading to the production of biochar. This study reports experiments conducted on the production of freshwater and saltwater macroalgal biochar in pilot‐scale quantities, the physical and chemical characteristics of the biochars, and their impact on plant growth. The biochars are low in carbon (C) content, surface area and cation exchange capacity, while being high in ash and nutrients. Trace element analysis demonstrates that macroalgal biochar produced from unpolluted water does not contain toxic trace elements in excess of levels mandated for unrestricted use as a biosolids amendment to soils. Pot trials conducted using a C and nutrient‐poor soil, without and with additional fertilizer, demonstrate dramatic increases between 15 and 32 times, respectively, in plant growth rate for biochar treatments compared with the no biochar controls, with additional smaller increases when fertilizer was added. Pot trials conducted using a relatively fertile agricultural soil showed smaller but significant impacts of biochar amendment over the controls.
Sildenafil improves diabetic vascular activity through suppressing endothelin receptor A, iNOS and NADPH oxidase which is comparable with the endothelin receptor antagonist CPU0213 in STZ-injected rats
Authors: Luo Lu , Dai De-Zai , Cheng Yu-Si , Zhang Qi , Yuan Wen-Jun , Dai Yin 
Published: June 2011

Abstract

Objectives
Abnormal vascular activity in diabetes is related not only to impaired nitric oxide bioavailability but also to inflammatory cytokines, endothelin A receptor (ETA) activation and NADPH oxidase in the vasculature. The potential role of sildenafil in improving vascular function was investigated. Its action was likely blocking upregulated ETA and NADPH oxidase, and was compared with the endothelin receptor antagonist CPU0213.

Methods
Diabetes was induced by single-dose administration of streptozotocin (65 mg/kg, i.p.) to rats and the vascular activity of the thoracic aorta was measured.

Key findings
An increase in contractile tone to phenylephrine and a decrease in relaxant tone to acetylcholine was found in the thoracic aorta. Oxidative stress was evident by increased malondialdehyde and reduced glutathione peroxidase levels in serum and upregulation of ETA, MMP-9 (matrix metalloproteinase-9), inducible nitric oxide synthase and NADPH oxidase p67phox were found in the vascular wall. The vascular abnormalities and abnormal biomarkers were attenuated significantly by either sildenafil or CPU0213 along with an improvement of nitric oxide bioavailability and vascular activity.

Conclusions
Improvement of diabetic vascular abnormal activity by sildenafil results from its suppression of activation of ETA and NADPH oxidase in the vasculature, and these actions are comparable with those of the endothelin receptor antagonist CPU0213.
Harnessing the Glucosyltransferase Activities of Clostridium difficile for Functional Studies of Toxins A and B
Authors: Darkoh Charles , Kaplan Heidi B. , DuPont Herbert L. 
Published: June 2011

ABSTRACT

The incidence of
Clostridium difficile
infection (CDI) has been increasing within the last decade. Pathogenic strains of
C. difficile
produce toxin A and/or toxin B, which are important virulence factors in the pathogenesis of this bacterium. Current methods for diagnosing CDI are mostly qualitative tests that detect either the bacterium or the toxins. We have developed an assay (Cdifftox activity assay) to detect
C. difficile
toxin A and B activities that is quantitative and cost-efficient and utilizes a substrate that is stereochemically similar to the native substrate of the toxins (UDP-glucose). To characterize toxin activity, toxins A and B were purified from culture supernatants by ammonium sulfate precipitation and chromatography through DEAE-Sepharose and gel filtration columns. The activities of the final fractions were quantitated using the Cdifftox activity assay and compared to the results of a toxin A- and B-specific enzyme-linked immunosorbent assay (ELISA). The affinity for the substrate was >4-fold higher for toxin B than for toxin A. Moreover, the rate of cleavage of the substrate was 4.3-fold higher for toxin B than for toxin A. The optimum temperature for both toxins ranged from 35 to 40°C at pH 8. Culture supernatants from clinical isolates obtained from the stools of patients suspected to be suffering from CDI were tested using the Cdifftox activity assay, and the results were compared to those of ELISA and PCR amplification of the toxin genes. Our results demonstrate that this new assay is comparable to the current commercial ELISA for detecting the toxins in the samples tested and has the added advantage of quantitating toxin activity.
Incidence of Moxifloxacin Resistance in Clinical Mycobacterium tuberculosis Isolates in Houston, Texas
Authors: El Sahly Hana M. , Teeter Larry D. , Jost Kenneth C. , Dunbar Denise , Lew Justin , Graviss Edward A. 
Published: June 2011

ABSTRACT

Comprehensive data on the prevalence of quinolone resistance in
Mycobacterium tuberculosis
clinical isolates in the United States are scarce. By use of a systematic population-based approach,
M. tuberculosis
strains from tuberculosis (TB) cases were collected in Harris County, TX, in 2007 to 2008. The susceptibilities of
M. tuberculosis
isolates to moxifloxacin and ofloxacin were determined by the agar proportion indirect susceptibility method. Spoligotyping and 12-locus mycobacterial interspersed repetitive unit (MIRU12)-based genotyping of
M. tuberculosis
isolates were performed, and the
gyrA
,
gyrB
, Rv2686c, Rv2687c, and Rv2688c genes in quinolone-resistant and year-of-diagnosis-matched
M. tuberculosis
isolates were sequenced. Susceptibility testing was performed on 557
M. tuberculosis
isolates, of which 10 (1.8%) were resistant to moxifloxacin. There was 100% concordance between ofloxacin and moxifloxacin susceptibilities. A quinolone was prescribed to at least 5 (50%) patients in the period preceding TB diagnosis. Multidrug-resistant TB (MDR-TB) was significantly associated with quinolone resistance (
P
= 0.01). Mutations in the quinolone resistance-determining region of
gyrA
were found for 50% of the resistant isolates. No other presumptive quinolone resistance-associated mutations were identified. We conclude that the incidence of moxifloxacin-resistant TB is low in Harris County and is associated with MDR-TB. Previous exposure to quinolones is common among patients with moxifloxacin resistance and warrants more careful evaluation.
Prototheca wickerhamii Mimicking Yeast: a Cautionary Tale
Authors: McMullan B. , Muthiah K. , Stark D. , Lee L. , Marriott D. 
Published: June 2011

ABSTRACT

Prototheca
spp. are environmental algae that may cause serious infection in the immunocompromised patient. Clinical manifestations may mimic other diseases. We present a case of fatal infection in a 78-year-old cardiac transplant recipient and discuss pitfalls in the clinical and laboratory diagnoses.
Identification by 16S rRNA Gene Sequencing of Negativicoccus succinicivorans Recovered from the Blood of a Patient with Hemochromatosis and Pancreatitis
Authors: Church D. L. , Simmon K. E. , Sporina Jan , Lloyd T. , Gregson D. B. 
Published: June 2011

ABSTRACT

We describe a case of
Negativicoccus succinicivorans
bacteremia in an adult man with hemochromatosis and acute pancreatitis. Conventional phenotypic tests and commercial identification systems failed to definitively identify the tiny anaerobic Gram-negative coccus isolated from two sets of blood cultures. The bacterium was identified by 16S rRNA gene sequencing and analysis using the SmartGene Integrated Database Network System software. This is the first published report of the recovery of this organism from a patient with invasive infection.
The HIV-1-Specific Protein Casp8p41 Induces Death of Infected Cells through Bax/Bak
Authors: Sainski Amy M. , Natesampillai Sekar , Cummins Nathan W. , Bren Gary D. , Taylor Julie , Saenz Dyana T. , Poeschla Eric M. , Badley Andrew D. 
Published: June 2011

ABSTRACT

Casp8p41, a novel protein generated when HIV-1 protease cleaves caspase 8, independently causes NF-κB activation, proinflammatory cytokine production, and cell death. Here we investigate the mechanism by which Casp8p41 induces cell death. Immunogold staining and electron microscopy demonstrate that Casp8p41 localizes to mitochondria of activated primary CD4 T cells, suggesting mitochondrial involvement. Therefore, we assessed the dependency of Casp8p41-induced death on Bax/Bak and caspase 9. In wild-type (WT) mouse embryonic fibroblast (MEF) cells, Casp8p41 causes rapid mitochondrial depolarization (
P
< 0.001), yet Casp8p41 expression in Bax/Bak double-knockout (DKO) MEF cells does not. Similarly, caspase 9-deficient T cells (JMR cells), which express Casp8p41, undergo minimal cell death, whereas reconstituting these cells with caspase 9 (F9 cells) restores Casp8p41 cytotoxicity (
P
< 0.01). The infection of caspase 9-deficient cells with a green fluorescent protein (GFP) HIV-1 reporter virus results in cell death in 32% of infected GFP-positive cells, while the restoration of caspase 9 expression in these cells restores infected-cell killing to 68% (
P
< 0.05), with similar levels of viral replication between infections. Our data demonstrate that Casp8p41 requires Bax/Bak to induce mitochondrial depolarization, which leads to caspase 9 activation following either Casp8p41 expression or HIV-1 infection. This understanding allows the design of strategies to interrupt this form of death of HIV-1-infected cells.
The 6-PACK programme to decrease fall-related injuries in acute hospitals: protocol for a cluster randomised controlled trial: Figure 1
Authors: Barker Anna , Brand Caroline , Haines Terry , Hill Keith , Brauer Sandy , Jolley Damien , Botti Mari , Cumming Robert , Livingston Patricia M , Sherrington Cathie , Zavarsek Silva , Morello Renata , Kamar Jeannette 
Published: June 2011

Background and aimsIn-hospital fall-related injuries are a source of personal harm, preventable hospitalisation costs, and access block through increased length of stay. Despite increased fall prevention awareness and activity over the last decade, rates of reported fall-related fractures in hospitals appear not to have decreased. This cluster randomised controlled trial (RCT) aims to determine the efficacy of the 6-PACK programme for preventing fall-related injuries, and its generalisability to other acute hospitals.Methods24 acute medical and surgical wards from six to eight hospitals throughout Australia will be recruited for the study. Wards will be matched by type and fall-related injury rates, then randomly allocated to the 6-PACK intervention (12 wards) or usual care control group (12 wards). The 6-PACK programme includes a nine-item fall risk assessment and six nursing interventions: ‘falls alert’ sign; supervision of patients in the bathroom; ensuring patient's walking aids are within reach; establishment of a toileting regime; use of a low-low bed; and use of bed/chair alarm. Intervention wards will be supported by a structured implementation strategy. The primary outcomes are fall and fall-related injury rates 12 months following 6-PACK implementation.DiscussionThis study will involve approximately 16 000 patients, and as such is planned to be the largest hospital fall prevention RCT to be undertaken and the first to be powered for the important outcome of fall-related injuries. If effective, there is potential to implement the programme widely as part of daily patient care in acute hospital wards where fall-related injuries are a problem.Trial registrationThe protocol for this study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12611000332921).
Some Jewish thoughts on genetic enhancement
Authors: Glick Shimon M 
Published: June 2011

The issues of the ethics of germ line modification in general and of enhancement by germ line modification in particular have been the subject of hundreds of articles in the bioethical literature. Both because the techniques are far from perfected and because the potential long term side effects are unkown, there is a widespread consensus that germ line modification for enhancement is absolutely unethical and beyond the pale at the present time.The author considers a thought expperiment projecting into the future in which perhaps the safety and reversibility of germ line modification have been clearly demonstrated. Under such circumstances it is contended that the dividing line between treatment and enhancement is difficult and indeed perhaps impossible to maintain.The Jewish tradition is examined and from the various sources cited it would seem that the benefits of certain kinds of genetic enhancements might well outweigh the objections to such manipulations.
Treatment of two blood blister-like aneurysms with flow diverter stenting
Authors: Consoli Arturo , Nappini Sergio , Renieri Leonardo , Limbucci Nicola , Ricciardi Fabrizio , Mangiafico Salvatore 
Published: June 2011

PurposeNeurosurgical and endovascular treatment of fragile and recurrent aneurysms of the non-branching portion of the internal carotid artery, known as blister-like aneurysms, is challenging. The aim of this paper is to describe two cases of ruptured blister-like aneurysms of the internal carotid artery and of the vertebral artery at the origin of the postero-inferior cerebellar artery, which were both treated with flow diverter (FD) stents.MethodsTwo patients with a sub-arachnoid hemorrhage secondary to the rupture of a blister-like aneurysm were treated with a Pipeline (ev3, Irvine, California, USA) stent. Digital subtraction angiography and clinical follow-up were carried out.ResultsBoth patients treated with FD stents had an excellent clinical (modified Rankin Scale, mRS 0) and angiographic outcome. In both cases the aneurysms were completely excluded after 6 months.ConclusionsAlthough the use of this endovascular approach is still debated because of poor experience and pharmacological limitations, FD stents may represent a valid alternative approach for treatment of this aneurysm subtype.
Mitoxantrone Inhibits HIF-1α Expression in a Topoisomerase II–Independent Pathway
Authors: Toh Yng-Miin , Li Tsai-Kun 
Published: June 2011

Abstract
Purpose: Solid tumors encounter a growth-limiting hypoxic microenvironment as they develop. Hypoxia-inducible factors (HIF) play important roles in hypoxia-associated tumor development and therapeutic resistance. Targeting the HIF pathway (especially HIF-1α) represents a promising cancer treatment strategy. Here, we report a novel class of HIF-1α inhibitors and the possible molecular basis of inhibition.
Experimental Design: We analyzed the inhibitory effects of clinically used topoisomerase II (TOP2)–targeting drugs on HIF-1α expression with a primary focus on mitoxantrone. The potential role of TOP2 in mitoxantrone-inhibited HIF-1α expression was studied using pharmacologic inhibition, a knockdown approach, and TOP2 mutant cells. Moreover, involvement of mitoxantrone in proteasome-mediated degradation, transcription, and translation of HIF-1α was examined.
Results: The TOP2-targeting mitoxantrone, but neither doxorubicin nor etoposide (VP-16), strongly inhibited HIF-1α expression under hypoxic conditions in a dose- and time-dependent manner. Surprisingly, the mitoxantrone-mediated inhibition of HIF-1α expression was largely independent of two TOP2 isozymes, proteasomal degradation, and transcription. Furthermore, mitoxantrone inhibited HIF-1α expression and function in a similar fashion as cycloheximide, suggesting that mitoxantrone might inhibit HIF-1α via a blockage at its translation step. In vitro translation experiments using HIF-1α mRNA further confirmed inhibition of HIF-1α translation by mitoxantrone. Interestingly, levels of the polysome-bound HIF-1α and VEGF-A mRNA were elevated and decreased after mitoxantrone treatment, respectively.
Conclusions: We have identified the TOP2-targeting compound, mitoxantrone, as an HIF-1α inhibitor possibly through a translation inhibition mechanism, suggesting the possibility of an additional anticancer activity for mitoxantrone. Clin Cancer Res; 17(15); 5026–37. ©2011 AACR.
Platelet factor XIII gene expression and embolic propensity in atrial fibrillation
Authors: Gosk-Bierska Izabella , McBane Robert D. , Wu Yanhong , Mruk Jozef , Tafur Alfonso , McLeod Thomas , Wysokinski Waldemar E. 
Published: June 2011

SummaryNearly 15% of patients with non-valvular atrial fibrillation (NVAF) have left atrial appendage thrombus (LAAT) by transesophageal echocardiography (TEE) and yet the annual stroke rate averages 5%. The aim of this study was to identify variables influencing embolic propensity of LAAT. Platelet RNA was extracted from platelet-rich regions within formalin- fixed, paraffin-embedded specimens obtained from NVAF patients during cardiac surgery (26 LAAT from 23 patients) or peripheral embolectomy (51 thrombi from 41 patients). Platelet RNA was also assessed from whole blood from 40 NVAF patients. Expression of six platelet- predominate genes: H2A histone family, A1 domain of factor XIII, integrin α2bβ3; glycoprotein IX, platelet factor 4, glycoprotein Ib, was performed using TaqMan MGB-probe based quantitative real-time polymerase chain reaction. Platelet factor XIII subunit A gene expression was significantly lower in embolised compared to non-embolised thrombi as determined by normalised cycle threshold values (4.0 ± 1.2 v 2.8 ± 1.8, p=0.02). Expression of other genes did not differ by embolic status. In conclusion, RNA extracted from formalin-fixed, paraffin-embedded platelet-rich tissues can be used for analysis of platelet- predominate gene expression. Variable factor XIII gene expression in thrombi generated during NVAF may in part explain the propensity to embolisation.
Longer legs are associated with greater risk of incident venous thromboembolism independent of total body height
Authors: Cushman Mary , Heckbert Susan R. , Tang Weihong , Folsom Aaron R. , Lutsey Pamela L. 
Published: June 2011

SummarySeveral studies have reported that taller individuals are at greater risk of venous thromboembolism (VTE). We hypothesised that longer leg length would be positively associated with incident VTE, and would explain the height association. LITE ascertained VTE in a prospective population-based sample of 21,860 individuals aged 45 and older. Leg length was measured as standing height minus torso length. Cox regression models were adjusted for age, race, sex, waist circumference, diabetes, and factor VIII. To evaluate whether leg length was associated with VTE risk independent of height, we standardised leg length and height per 1 standard deviation (SD), and then included them simultaneously in Cox regression models. A total of 641 incident VTE cases accrued over a median follow-up of 16 years. Participants in the highestquintile of leg length were at 59% (95% CI: 22%-108%) greater risk of VTE, relative to the lowest quintile. For height, risk was 45% (12%-88%) greater for those in the highest quintile, compared to the lowest. When leg length and height were modelled simultaneously leg length remained associated with VTE risk (HR per 1 SD: 1.21 (1.04–1.40) while height was unrelated (HR per 1 SD: 1.00 (0.86–1.16). To conclude, participants with longer legs were at greater risk of incident VTE, and leg length explained the relation of height to VTE. It remains to be established whether this finding is due to greater venous surface area, a larger number of venous valves, or greater hydrostatic pressure among individuals with longer legs.