bluuebunny/crossref_metadata_2025 huggingface dataset:
Profound metabolic, functional, and cytolytic differences characterize HIV-specific CD8 T cells in primary and chronic HIV infection
Authors: Trautmann Lydie , Mbitikon-Kobo Florentin-Martial , Goulet Jean-Philippe , Peretz Yoav , Shi Yu , Van Grevenynghe Julien , Procopio Francesco Andrea , Boulassel Mohamad Rachid , Routy Jean-Pierre , Chomont Nicolas , Haddad Elias K. , Sekaly Rafick-Pierre
Published: September 2012

Immediate-early host-virus interactions that occur during the first weeks after HIV infection have a major impact on disease progression. The mechanisms underlying the failure of HIV-specific CD8 T-cell response to persist and control viral replication early in infection are yet to be characterized. In this study, we performed a thorough phenotypic, gene expression and functional analysis to compare HIV-specific CD8 T cells in acutely and chronically infected subjects. We showed that HIV-specific CD8 T cells in primary infection can be distinguished by their metabolic state, rate of proliferation, and susceptibility to apoptosis. HIV-specific CD8 T cells in acute/early HIV infection secreted less IFN-γ but were more cytotoxic than their counterparts in chronic infection. Importantly, we showed that the levels of IL-7R expression and the capacity of HIV-specific CD8 T cells to secrete IL-2 on antigenic restimulation during primary infection were inversely correlated with the viral set-point. Altogether, these data suggest an altered metabolic state of HIV-specific CD8 T cells in primary infection resulting from hyperproliferation and stress induced signals, demonstrate the discordant function of HIV-specific CD8 T cells during early/acute infection, and highlight the importance of T-cell maintenance for viral control.
Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP: report from an International DLBCL Rituximab-CHOP Consortium Program Study
Authors: Xu-Monette Zijun Y. , Wu Lin , Visco Carlo , Tai Yu Chuan , Tzankov Alexander , Liu Wei-min , Montes-Moreno Santiago , Dybkær Karen , Chiu April , Orazi Attilio , Zu Youli , Bhagat Govind , Richards Kristy L. , Hsi Eric D. , Zhao X. Frank , Choi William W. L. , Zhao Xiaoying , van Krieken J. Han , Huang Qin , Huh Jooryung , Ai Weiyun , Ponzoni Maurilio , Ferreri Andrés J. M. , Zhou Fan , Kahl Brad S. , Winter Jane N. , Xu Wei , Li Jianyong , Go Ronald S. , Li Yong , Piris Miguel A. , Møller Michael B. , Miranda Roberto N. , Abruzzo Lynne V. , Medeiros L. Jeffrey , Young Ken H.
Published: September 2012

TP53 mutation is an independent marker of poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (CHOP) therapy. However, its prognostic value in the rituximab immunochemotherapy era remains undefined. In the present study of a large cohort of DLBCL patients treated with rituximab plus CHOP (R-CHOP), we show that those with TP53 mutations had worse overall and progression-free survival compared with those without. Unlike earlier studies of patients treated with CHOP, TP53 mutation has predictive value for R-CHOP–treated patients with either the germinal center B-cell or activated B-cell DLBCL subtypes. Furthermore, we identified the loop-sheet-helix and L3 motifs in the DNA-binding domain to be the most critical structures for maintaining p53 function. In contrast, TP53 deletion and loss of heterozygosity did not confer worse survival. If gene mutation data are not available, immunohistochemical analysis showing > 50% cells expressing p53 protein is a useful surrogate and was able to stratify patients with significantly different prognoses. We conclude that assessment of TP53 mutation status is important for stratifying R-CHOP–treated patients into distinct prognostic subsets and has significant value in the design of future therapeutic strategies.
HTLV-1–infected T cells contain a single integrated provirus in natural infection
Authors: Cook Lucy B. , Rowan Aileen G. , Melamed Anat , Taylor Graham P. , Bangham Charles R. M.
Published: September 2012

Human T lymphotropic virus type 1 (HTLV-1) appears to persist in the chronic phase of infection by driving oligoclonal proliferation of infected T cells. Our recent high-throughput sequencing study revealed a large number (often > 104) of distinct proviral integration sites of HTLV-1 in each host that is greatly in excess of previous estimates. Here we use the highly sensitive, quantitative high-throughput sequencing protocol to show that circulating HTLV-1+ clones in natural infection each contain a single integrated proviral copy. We conclude that a typical host possesses a large number of distinct HTLV-1–infected T-cell clones.
Translation and adaption of the interRAI suite to local requirements in Belgian hospitals
Authors: Wellens Nathalie IH , Flamaing Johan , Moons Philip , Deschodt Mieke , Boonen Steven , Milisen Koen
Published: September 2012

Background

The interRAI Suite contains comprehensive geriatric assessment tools designed for various healthcare settings. Although each instrument is developed for a particular population, together they form an integrated health evaluation system. The interRAI Acute Care Minimum Data Set (interRAI AC) is tailored for hospitalized older persons. Our aim in this study was to translate and adapt the interRAI AC to the Belgian hospital context, where it can be used together with the interRAI Home Care (HC) and the interRAI Long Term Care Facility (LTCF).

Methods

A systematic, comprehensive, and rigorous 10-step approach was used to adapt the interRAI AC to local requirements. After linguistic translation by an official translator, five researchers assessed the translation for appropriate hospital jargon. Three researchers double-checked for translation accuracy and proposed additional items. A provisional version was converted into the three official languages of Belgium—Flemish, French, and German. Next, a multidisciplinary panel of nine experts judged item relevance to the Belgian care context and advised which country-specific items should be added. After these suggestions were incorporated into the interRAI AC, hospital staff from nine Flemish hospitals field-tested the tool in their practice. After evaluating field-test results, we compared the interRAI AC with Belgian versions of the interRAI HC and interRAI LTCF. Next, the Flemish, French, and German versions of the Belgian interRAI portfolio were harmonized. Finally, we submitted the Belgian interRAI AC to the interRAI organization for ratification.

Results

Eighteen administrative items of the interRAI AC were adapted to the Belgian healthcare context (e.g., usual residence, formal community services prior to admission). Fourteen items assessing the ‘informal caregiver’, and 17 items, including country-specific items, were added (e.g., advanced directive for euthanasia).

Conclusions

The interRAI AC was adapted to local requirements using a meticulous and recursive 10-step approach. As use of the interRAI Suite continues to grow worldwide and as it continues to expand to other care settings and populations, this procedure can guide future translations. This procedure might also be used by others facing similar challenges of complex translation and adaptation situations, where multidimensional instruments are used across multiple care settings in multiple languages.
Impact of mannose-binding lectin deficiency on radiocontrast-induced renal dysfunction: a post-hoc analysis of a multicenter randomized controlled trial
Authors: Osthoff Michael , Piezzi Vanja , Klima Theresia , Christ Andreas , Marana Ivana , Hartwiger Sabine , Breidthardt Tobias , Marenzi Giancarlo , Trendelenburg Marten , Mueller Christian
Published: September 2012

Background

Local renal ischemia is regarded as an important factor in the development of contrast-induced nephropathy (CIN). Mannose-binding lectin (MBL) is involved in the tissue damage during experimental ischemia/reperfusion injury of the kidneys. The aim of the present study was to investigate the association of MBL deficiency with radiocontrast-induced renal dysfunction in a large prospective cohort.

Methods

246 patients with advanced non–dialysis-dependent renal dysfunction who underwent radiographic contrast procedures were included in the study. Baseline serum MBL levels were analyzed according to the occurrence of a creatinine-based (increase of ≥0.5 mg/dL or ≥25% within 48 hours) or cystatin C-based (increase of ≥10% within 24 hours) CIN.

Results

The incidence of creatinine-based and cystatin C-based CIN was 6.5% and 24%, respectively. MBL levels were not associated with the occurrence of creatinine-based CIN. However, patients that experienced a cystatin C increase of ≥10% showed significantly higher MBL levels than patients with a rise of <10% (median 2885 (IQR 1193–4471) vs. 1997 (IQR 439–3504)ng/mL, p = 0.01). In logistic regression analysis MBL deficiency (MBL levels≤500 ng/ml) was identified as an inverse predictor of a cystatin C increase ≥10% (OR 0.34, 95% CI 0.15-0.8, p = 0.01).

Conclusion

MBL deficiency was associated with a reduced radiocontrast-induced renal dysfunction as reflected by the course of cystatin C. Our findings support a possible role of MBL in the pathogenesis of CIN.
Suboptimal management of central nervous system infections in children: a multi-centre retrospective study
Authors: Kelly Christine , Sohal Aman , Michael Benedict D , Riordan Andrew , Solomon Tom , Kneen Rachel ,   Northwest Neurological Infections Network
Published: September 2012

Objective

We aimed to audit the regional management of central nervous system (CNS) infection in children.

Methods

The study was undertaken in five district general hospitals and one tertiary paediatric hospital in the Mersey region of the UK. Children admitted to hospital with a suspected CNS infection over a three month period were identified. Children were aged between 4 weeks and 16 years old. Details were recorded from the case notes and electronic records. We measured the appropriateness of management pathways as outlined by national and local guidelines.

Results

Sixty-five children were identified with a median age of 6 months (range 1 month to 15 years). Ten had a CNS infection: 4 aseptic meningitis, 3 purulent meningitis, 3 encephalitis [2 with herpes simplex virus (HSV) type 1]. A lumbar puncture (LP) was attempted in 50 (77%) cases but only 43 had cerebrospinal fluid (CSF) available for analysis. Of these 24 (57%) had a complete standard set of tests performed. Fifty eight (89%) received a third generation cephalosporin. Seventeen (26%) also received aciclovir with no obvious indication in 9 (53%). Only 11 (65%) of those receiving aciclovir had CSF herpes virus PCR. Seventeen had cranial imaging and it was the first management step in 14. Treatment lengths of both antibiotics and aciclovir were highly variable: one child with HSV encephalitis was only treated with aciclovir for 7 days.

Conclusions

The clinical management of children with suspected CNS infections across the Mersey region is heterogeneous and often sub-optimal, particularly for the investigation and treatment of viral encephalitis. National guidelines for the management of viral encephalitis are needed.
Appropriate use of indwelling urethra catheters in hospitalized patients: results of a multicentre prevalence study
Authors: Jansen Irálice AV , Hopmans Titia EM , Wille Jan C , van den Broek Peterhans J , van der Kooi Tjallie II , van Benthem Birgit HB
Published: September 2012

Background

Although indwelling urethra catheterization is a medical intervention with well-defined risks, studies show that approximately 14–38% of the indwelling urethra catheters (IUCs) are placed without a specific medical indication. In this paper we describe the prevalence of IUCs, including their inappropriate use in the Netherlands. We also determine factors associated with inappropriate use of IUCs in hospitalized patients.

Methods

In 28 Dutch hospitals, prevalence surveys were performed biannually in 2009 and 2010 within the PREZIES-network. All patients admitted to a participating hospital and who had an IUC in place at the day of the survey were included. Pre-determined criteria were used to categorize the indication for catheterization as appropriate or inappropriate.

Results

A total of 14,252 patients was included and 3020 (21.2%) of them had an IUC (range hospitals 13.4-27.3). Initial catheter placement was inappropriate in 5.2% of patients and 7.5% patients had an inappropriate indication at the day of the survey. In multivariate analyses inappropriate catheter use at the time of placement was associated with female sex, older age, admission on a non-intensive care ward, and not having had surgery. Inappropriate catheter use at the time of survey showed comparable associated factors.

Conclusions

Although lower than in many other countries, inappropriate use of IUC is present in Dutch hospitals. To reduce the inappropriate use of IUCs, recommended components of care (bundle for UTI), including daily revision and registration of the indication for catheterization, should be introduced for all patients with an IUC. Additionally, an education and awareness campaign about appropriate indications for IUC should be available.
Rotavirus A-specific single-domain antibodies produced in baculovirus-infected insect larvae are protective in vivo
Authors: Gómez-Sebastián Silvia , Nuñez Maria C , Garaicoechea Lorena , Alvarado Carmen , Mozgovoj Marina , Lasa Rodrigo , Kahl Alan , Wigdorovitz Andres , Parreño Viviana , Escribano José M
Published: September 2012

Background

Single-domain antibodies (sdAbs), also known as nanobodies or VHHs, are characterized by high stability and solubility, thus maintaining the affinity and therapeutic value provided by conventional antibodies. Given these properties, VHHs offer a novel alternative to classical antibody approaches. To date, VHHs have been produced mainly in E. coli, yeast, plants and mammalian cells. To apply the single-domain antibodies as a preventive or therapeutic strategy to control rotavirus infections in developing countries (444,000 deaths in children under 5 years of age) has to be minimized their production costs.

Results

Here we describe the highly efficient expression of functional VHHs by the Improved Baculovirus Expression System (IBES® technology), which uses a baculovirus expression vector in combination with Trichoplusia ni larvae as living biofactories. Two VHHs, named 3B2 and 2KD1, specific for the inner capsid protein VP6 of Group A rotavirus, were expressed in insect larvae. The IBES® technology achieved very high expression of 3B2 and 2KD1, reaching 2.62% and 3.63% of the total soluble protein obtained from larvae, respectively. These expression levels represent up to 257 mg/L of protein extract after insect processing (1 L extract represents about 125 g of insect biomass or about 375 insect larvae). Larva-derived antibodies were fully functional when tested in vitro and in vivo, neutralizing Group A rotaviruses and protecting offspring mice against rotavirus-induced diarrhea.

Conclusions

Our results open up the possibility of using insects as living biofactories (IBES® technology) for the cost-efficient production of these and other fully functional VHHs to be used for diagnostic or therapeutic purposes, thereby eliminating concerns regarding the use of bacterial or mammalian cells. To the best of our knowledge, this is the first time that insects have been used as living biofactories to produce a VHH molecule.
Boundaries and e-health implementation in health and social care
Authors: King Gerry , O’Donnell Catherine , Boddy David , Smith Fiona , Heaney David , Mair Frances S
Published: September 2012

Background

The major problem facing health and social care systems globally today is the growing challenge of an elderly population with complex health and social care needs. A longstanding challenge to the provision of high quality, effectively coordinated care for those with complex needs has been the historical separation of health and social care. Access to timely and accurate data about patients and their treatments has the potential to deliver better care at less cost.

Methods

To explore the way in which structural, professional and geographical boundaries have affected e-health implementation in health and social care, through an empirical study of the implementation of an electronic version of Single Shared Assessment (SSA) in Scotland, using three retrospective, qualitative case studies in three different health board locations.

Results

Progress in effectively sharing electronic data had been slow and uneven. One cause was the presence of established structural boundaries, which lead to competing priorities, incompatible IT systems and infrastructure, and poor cooperation. A second cause was the presence of established professional boundaries, which affect staffs’ understanding and acceptance of data sharing and their information requirements. Geographical boundaries featured but less prominently and contrasting perspectives were found with regard to issues such as co-location of health and social care professionals.

Conclusions

To provide holistic care to those with complex health and social care needs, it is essential that we develop integrated approaches to care delivery. Successful integration needs practices such as good project management and governance, ensuring system interoperability, leadership, good training and support, together with clear efforts to improve working relations across professional boundaries and communication of a clear project vision. This study shows that while technological developments make integration possible, long-standing boundaries constitute substantial risks to IT implementations across the health and social care interface which those initiating major changes would do well to consider before committing to the investment.
Erythropoietin attenuates cardiac dysfunction by increasing myocardial angiogenesis and inhibiting interstitial fibrosis in diabetic rats
Authors: Lu Jing , Yao Yu-yu , Dai Qi-ming , Ma Gen-shan , Zhang Shu-feng , Cao Lei , Ren Li-qun , Liu Nai-feng
Published: September 2012

Background

Recent studies revealed that erythropoietin (EPO) has tissue-protective effects in the heart by increasing vascular endothelial growth factor (VEGF) expression and attenuating myocardial fibrosis in ischemia models. In this study, we investigated the effect of EPO on ventricular remodeling and blood vessel growth in diabetic rats.

Methods

Male SD rats were randomly divided into 3 groups: control rats, streptozotocin (STZ)-induced diabetic rats, and diabetic rats treated with 1000 U/kg EPO by subcutaneous injection once per week. Twelve weeks later, echocardiography was conducted, and blood samples were collected for counting of peripheral blood endothelial progenitor cells (EPCs). Myocardial tissues were collected, quantitative real-time PCR (RT-PCR) was used to detect the mRNA expression of VEGF and EPO-receptor (EPOR), and Western blotting was used to detect the protein expression of VEGF and EPOR. VEGF, EPOR, transforming growth factor beta (TGF-β), and CD31 levels in the myocardium were determined by immunohistochemistry. To detect cardiac hypertrophy, immunohistochemistry of collagen type I, collagen type III, and Picrosirius Red staining were performed, and cardiomyocyte cross-sectional area was measured.

Results

After 12 weeks STZ injection, blood glucose increased significantly and remained consistently elevated. EPO treatment significantly improved cardiac contractility and reduced diastolic dysfunction. Rats receiving the EPO injection showed a significant increase in circulating EPCs (27.85 ± 3.43%, P < 0.01) compared with diabetic untreated animals. EPO injection significantly increased capillary density as well as EPOR and VEGF expression in left ventricular myocardial tissue from diabetic rats. Moreover, EPO inhibited interstitial collagen deposition and reduced TGF-β expression.

Conclusions

Treatment with EPO protects cardiac tissue in diabetic animals by increasing VEGF and EPOR expression levels, leading to improved revascularization and the inhibition of cardiac fibrosis.
The global pipeline of new medicines for the control and elimination of malaria
Authors: Anthony Melinda P , Burrows Jeremy N , Duparc Stephan , JMoehrle Joerg , Wells Timothy NC
Published: September 2012

Over the past decade, there has been a transformation in the portfolio of medicines to combat malaria. New fixed-dose artemisinin combination therapy is available, with four different types having received approval from Stringent Regulatory Authorities or the World Health Organization (WHO). However, there is still scope for improvement. The Malaria Eradication Research agenda identified several gaps in the current portfolio. Simpler regimens, such as a single-dose cure are needed, compared with the current three-day treatment. In addition, new medicines that prevent transmission and also relapse are needed, but with better safety profiles than current medicines. There is also a big opportunity for new medicines to prevent reinfection and to provide chemoprotection. This study reviews the global portfolio of new medicines in development against malaria, as of the summer of 2012. Cell-based phenotypic screening, and ‘fast followers’ of clinically validated classes, mean that there are now many new classes of molecules starting in clinical development, especially for the blood stages of malaria. There remain significant gaps for medicines blocking transmission, preventing relapse, and long-duration molecules for chemoprotection. The nascent pipeline of new medicines is significantly stronger than five years ago. However, there are still risks ahead in clinical development and sustainable funding of clinical studies is vital if this early promise is going to be delivered.
Toxicity of oxidized phospholipids in cultured macrophages
Authors: Stemmer Ute , Dunai Zsuzsanna A , Koller Daniel , Pürstinger Gabriel , Zenzmaier Elfriede , Deigner Hans P , Aflaki Elma , Kratky Dagmar , Hermetter Albin
Published: September 2012

Background

The interactions of oxidized low-density lipoprotein (LDL) and macrophages are hallmarks in the development of atherosclerosis. The biological activities of the modified particle in these cells are due to the content of lipid oxidation products and apolipoprotein modification by oxidized phospholipids.

Results

It was the aim of this study to determine the role of short-chain oxidized phospholipids as components of modified LDL in cultured macrophages. For this purpose we investigated the effects of the following oxidized phospholipids on cell viability and apoptosis: 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC), 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) and oxidized alkylacyl phospholipids including 1-O-hexadecyl-2-glutaroyl-sn-glycero-3-phosphocholine (E-PGPC) and 1-O-hexadecyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (E-POVPC). We found that these compounds induced apoptosis in RAW264.7 and bone marrow-derived macrophages. The sn- 2 carboxyacyl lipid PGPC was more toxic than POVPC which carries a reactive aldehyde function in position sn- 2 of glycerol. The alkylacyl phospholipids (E-PGPC and E-POVPC) and the respective diacyl analogs show similar activities. Apoptosis induced by POVPC and its alkylether derivative could be causally linked to the fast activation of an acid sphingomyelinase, generating the apoptotic second messenger ceramide. In contrast, PGPC and its ether analog only negligibly affected this enzyme pointing to an entirely different mechanism of lipid toxicity. The higher toxicity of PGPC is underscored by more efficient membrane blebbing from apoptotic cells. In addition, the protein pattern of PGPC-induced microparticles is different from the vesicles generated by POPVC.

Conclusions

In summary, our data reveal that oxidized phospholipids induce apoptosis in cultured macrophages. The mechanism of lipid toxicity, however, largely depends on the structural features of the oxidized sn- 2 chain.
Doxycycline impairs neutrophil migration to the airspaces of the lung in mice exposed to intratracheal lipopolysaccharide
Authors: Moon Andres , Gil Sucheol , Gill Sean E , Chen Peter , Matute-Bello Gustavo
Published: September 2012

Background

Tetracyclines are broad-spectrum antibiotics that are also used to induce gene expression using the reverse tetracycline transactivator / tetracycline operator system (rtTA/tetO system). The system assumes that tetracyclines have no effects on mammals. However, a number of studies suggest that tetracyclines may have powerful anti-inflammatory effects. We report that the tetracycline, doxycycline, inhibits neutrophil (PMN) influx into the lungs of mice treated with bacterial endotoxin (LPS).

Methods

Mice were challenged with intratracheal LPS in the presence or absence of doxycyline. bronchoalveolar lavage cell counts and differential, total bronchoalveolar lavage protein, lung homogenate caspase-3 and tissue imaging were used to assess lung injury. In addition, PMN chemotaxis was measured in vitro and syndecan-1 was measured in bronchoalveolar lavage fluid.

Results

The administration of doxycycline resulted in a significant decrease in the number of bronchoalveolar lavage PMNs in LPS-treated mice. Doxycycline had no effect on other markers of lung injury such as total bronchoalveolar lavage protein and whole lung caspase-3 activity. However, doxycycline resulted in a decrease in shed syndecan-1 in bronchoalveolar lavage fluid.

Conclusion

We conclude that doxycycline has an important anti-inflammatory effect that can potentially confound the experiments in which the rtTA/tetO system is being used to study the immune response.
Solvability of right focal boundary value problems with superlinear growth conditions
Authors: Pei Minghe , Chang Sung Kag , Oh Young Sun
Published: September 2012

In this paper, we consider n th-order two-point right focal boundary value problems

"Equation missing"

where

f
:
[
0
,
1
]
×

R
n

→
R

is a

L
p

-Carathéodory (

1
≤
p
<
∞

) function and satisfies superlinear growth conditions. The existence and uniqueness of solutions for the above right focal boundary value problems are obtained by Leray-Schauder continuation theorem and analytical technique. Meanwhile, as an application of our results, examples are given.

MSC:34B15.
Existence of solutions for a coupled system of fractional differential equations at resonance
Authors: Hu Zhigang , Liu Wenbin , Chen Taiyong
Published: September 2012

In this paper, by using the coincidence degree theory, we study the existence of solutions for a coupled system of fractional differential equations at resonance. A new result on the existence of solutions for a fractional boundary value problem is obtained.

MSC:34B15.
A novel method in adaptive image enlargement
Authors: Bayat Mozhgan , Kafaie Ghazaleh , Ayremlou Ali , Marvasti Farrokh
Published: September 2012

This article introduces a new adaptive method for image interpolation. In order to obtain a high resolution (HR) image from its low resolution (LR) counterpart (original image), an interpolator function (array) is used, and the main focus of this manuscript is to formulate and define this function. By applying this interpolator function to each row and column of a LR image, it is possible to construct its HR counterpart. One of the main challenges of image interpolation algorithms is to maintain the edge structures while developing an HR image from the LR replica. The proposed approach overcomes this challenge and exhibits remarkable results at the image edges. The peak signal to noise ratio and structural similarity criteria by using this innovative technique are notably better than those achieved by alternative schemes. Also, in terms of implementation speed, this method displays a clear advantage and outperforms the high performance algorithms in the ability to decrease the artifact results of image enlargement such as blurring and zigzagging.
Neuroinflammation and oxidative stress in rostral ventrolateral medulla contribute to neurogenic hypertension induced by systemic inflammation
Authors: Wu Kay LH , Chan Samuel HH , Chan Julie YH
Published: September 2012

Background

In addition to systemic inflammation, neuroinflammation in the brain, which enhances sympathetic drive, plays a significant role in cardiovascular diseases, including hypertension. Oxidative stress in rostral ventrolateral medulla (RVLM) that augments sympathetic outflow to blood vessels is involved in neural mechanism of hypertension. We investigated whether neuroinflammation and oxidative stress in RVLM contribute to hypertension following chronic systemic inflammation.

Methods

In normotensive Sprague-Dawley rats, systemic inflammation was induced by infusion of Escherichia coli lipopolysaccharide (LPS) into the peritoneal cavity via an osmotic minipump. Systemic arterial pressure and heart rate were measured under conscious conditions by the non-invasive tail-cuff method. The level of the inflammatory markers in plasma or RVLM was analyzed by ELISA. Protein expression was evaluated by Western blot or immunohistochemistry. Tissue level of superoxide anion (O2
·-) in RVLM was determined using the oxidation-sensitive fluorescent probe dihydroethidium. Pharmacological agents were delivered either via infusion into the cisterna magna with an osmotic minipump or microinjection bilaterally into RVLM.

Results

Intraperitoneal infusion of LPS (1.2 mg/kg/day) for 14 days promoted sustained hypertension and induced a significant increase in plasma level of C-reactive protein, tumor necrosis factor-α (TNF-α), or interleukin-1β (IL-1β). This LPS-induced systemic inflammation was accompanied by activation of microglia, augmentation of IL-1β, IL-6, or TNF-α protein expression, and O2
·- production in RVLM, all of which were blunted by intracisternal infusion of a cycloxygenase-2 (COX-2) inhibitor, NS398; an inhibitor of microglial activation, minocycline; or a cytokine synthesis inhibitor, pentoxifylline. Neuroinflammation in RVLM was also associated with a COX-2-dependent downregulation of endothelial nitric oxide synthase and an upregulation of intercellular adhesion molecule-1. Finally, the LPS-promoted long-term pressor response and the reduction in expression of voltage-gated potassium channel, Kv4.3 in RVLM were antagonized by minocycline, NS398, pentoxifylline, or a superoxide dismutase mimetic, tempol, either infused into cisterna magna or microinjected bilaterally into RVLM. The same treatments, on the other hand, were ineffective against LPS-induced systemic inflammation.

Conclusion

These results suggest that systemic inflammation activates microglia in RVLM to induce COX-2-dependent neuroinflammation that leads to an increase in O2
·- production. The resultant oxidative stress in RVLM in turn mediates neurogenic hypertension.
One-step detection of Bean pod mottle virusin soybean seeds by the reverse-transcription loop-mediated isothermal amplification
Authors: Wei Qi-Wei , Yu Cui , Zhang Shu-Ya , Yang Cui-Yun , Miriam Karwitha , Zhang Wen-Na , Dou Dao-Long , Tao Xiao-Rong
Published: September 2012

Background

Bean pod mottle virus (BPMV) is a wide-spread and destructive virus that causes huge economic losses in many countries every year. A sensitive, reliable and specific method for rapid surveillance is urgently needed to prevent further spread of BPMV.

Methods

A degenerate reverse-transcription loop-mediated isothermal amplification (RT-LAMP) primer set was designed on the conserved region of BPMV CP gene. The reaction conditions of RT-LAMP were optimized and the feasibility, specificity and sensitivity of this method to detect BPMV were evaluated using the crude RNA rapidly extracted from soybean seeds.

Results

The optimized RT-LAMP parameters including 6 mM MgCl2, 0.8 M betaine and temperature at 62.5-65°C could successfully amplify the ladder-like bands from BPMV infected soybean seeds. The amplification was very specific to BPMV that no cross-reaction was observed with other soybean viruses. Inclusion of a fluorescent dye makes it easily be detected in-tube by naked eye. The sensitivity of RT-LAMP assay is higher than the conventional RT-PCR under the conditions tested, and the conventional RT-PCR couldn’t be used for detection of BPMV using crude RNA extract from soybean seeds.

Conclusion

A highly efficient and practical method was developed for the detection of BPMV in soybean seeds by the combination of rapid RNA extraction and RT-LAMP. This RT-LAMP method has great potential for rapid BPMV surveillance and will assist in preventing further spread of this devastating virus.
Barley callus: a model system for bioengineering of starch in cereals
Authors: Carciofi Massimiliano , Blennow Andreas , Nielsen Morten M , Holm Preben B , Hebelstrup Kim H
Published: September 2012

Background

Starch is the most important source of calories for human nutrition and the majority of it is produced by cereal farming. Starch is also used as a renewable raw material in a range of industrial sectors. It can be chemically modified to introduce new physicochemical properties. In this way starch is adapted to a variety of specific end-uses. Recombinant DNA technologies offers an alternative to starch industrial processing. The plant biosynthetic pathway can be manipulated to design starches with novel structure and improved technological properties. In the future this may reduce or eliminate the economical and environmental costs of industrial modification. Recently, many advances have been achieved to clarify the genetic mechanism that controls starch biosynthesis. Several genes involved in the synthesis and modification of complex carbohydrates in many organisms have been identified and cloned. This knowledge suggests a number of strategies and a series of candidate genes for genetic transformation of crops to generate new types of starch-based polymers. However transformation of cereals is a slow process and there is no easy model system available to test the efficiency of candidate genes in planta.

Results

We explored the possibility to use transgenic barley callus generated from immature embryo for a fast test of transgenic modification strategies of starch biosynthesis. We found that this callus contains 4% (w/w dw) starch granules, which we could modify by generating fully transgenic calli by Agrobacterium-transformation. A Green Fluorescent Protein reporter protein tag was used to identify and propagate only fully transgenic callus explants. Around 1 – 1.5 g dry weight of fully transgenic callus could be produced in 9 weeks. Callus starch granules were smaller than endosperm starch granules and contained less amylose. Similarly the expression profile of starch biosynthesis genes were slightly different in callus compared with developing endosperm.

Conclusions

In this study we have developed an easy and rapid in planta model system for starch bioengineering in cereals. We suggest that this method can be used as a time-efficient model system for fast screening of candidate genes for the generation of modified starch or new types of carbohydrate polymers.
Proteomic analysis reveals resistance mechanism against biofuel hexane in Synechocystis sp. PCC 6803
Authors: Liu Jie , Chen Lei , Wang Jiangxin , Qiao Jianjun , Zhang Weiwen
Published: September 2012

Background

Recent studies have demonstrated that photosynthetic cyanobacteria could be an excellent cell factory to produce renewable biofuels and chemicals due to their capability to utilize solar energy and CO2 as the sole energy and carbon sources. Biosynthesis of carbon-neutral biofuel alkanes with good chemical and physical properties has been proposed. However, to make the process economically feasible, one major hurdle to improve the low cell tolerance to alkanes needed to be overcome.

Results

Towards the goal to develop robust and high-alkane-tolerant hosts, in this study, the responses of model cyanobacterial Synechocystis PCC 6803 to hexane, a representative of alkane, were investigated using a quantitative proteomics approach with iTRAQ - LC-MS/MS technologies. In total, 1,492 unique proteins were identified, representing about 42% of all predicted protein in the Synechocystis genome. Among all proteins identified, a total of 164 and 77 proteins were found up- and down-regulated, respectively. Functional annotation and KEGG pathway enrichment analyses showed that common stress responses were induced by hexane in Synechocystis. Notably, a large number of transporters and membrane-bound proteins, proteins against oxidative stress and proteins related to sulfur relay system and photosynthesis were induced, suggesting that they are possibly the major protection mechanisms against hexane toxicity.

Conclusion

The study provided the first comprehensive view of the complicated molecular mechanism employed by cyanobacterial model species, Synechocystis to defend against hexane stress. The study also provided a list of potential targets to engineer Synechocystis against hexane stress.
Peer2ref: a peer-reviewer finding web tool that uses author disambiguation
Authors: Andrade-Navarro Miguel A , Palidwor Gareth A , Perez-Iratxeta Carol
Published: September 2012

Background

Reviewer and editor selection for peer review is getting harder for authors and publishers due to the specialization onto narrower areas of research carried by the progressive growth of the body of knowledge. Examination of the literature facilitates finding appropriate reviewers but is time consuming and complicated by author name ambiguities.

Results

We have developed a method called peer2ref to support authors and editors in selecting suitable reviewers for scientific manuscripts. Peer2ref works from a text input, usually the abstract of the manuscript, from which important concepts are extracted as keywords using a fuzzy binary relations approach. The keywords are searched on indexed profiles of words constructed from the bibliography attributed to authors in MEDLINE. The names of these scientists have been previously disambiguated by coauthors identified across the whole MEDLINE. The methods have been implemented in a web server that automatically suggests experts for peer-review among scientists that have authored manuscripts published during the last decade in more than 3,800 journals indexed in MEDLINE.

Conclusion

peer2ref web server is publicly available at http://www.ogic.ca/projects/peer2ref/.
Spatial organization of the chicken beta-globin gene domain in erythroid cells of embryonic and adult lineages
Authors: Ulianov Sergey V , Gavrilov Alexey A , Razin Sergey V
Published: September 2012

Background

The β-globin gene domains of vertebrate animals constitute popular models for studying the regulation of eukaryotic gene transcription. It has previously been shown that in the mouse the developmental switching of globin gene expression correlates with the reconfiguration of an active chromatin hub (ACH), a complex of promoters of transcribed genes with distant regulatory elements. Although it is likely that observations made in the mouse β-globin gene domain are also relevant for this locus in other species, the validity of this supposition still lacks direct experimental evidence. Here, we have studied the spatial organization of the chicken β-globin gene domain. This domain is of particular interest because it represents the perfect example of the so-called ‘strong’ tissue-specific gene domain flanked by insulators, which delimit the area of preferential sensitivity to DNase I in erythroid cells.

Results

Using chromosome conformation capture (3C), we have compared the spatial configuration of the β-globin gene domain in chicken red blood cells (RBCs) expressing embryonic (3-day-old RBCs) and adult (9-day-old RBCs) β-globin genes. In contrast to observations made in the mouse model, we found that in the chicken, the early embryonic β-globin gene,Ε, did not interact with the locus control region in RBCs of embryonic lineage (3-day RBCs), where this gene is actively transcribed. In contrast to the mouse model, a strong interaction of the promoter of another embryonic β-globin gene,ρ, with the promoter of the adult β-globin gene,βA, was observed in RBCs from both 3-day and 9-day chicken embryos. Finally, we have demonstrated that insulators flanking the chicken β-globin gene domain from the upstream and from the downstream interact with each other, which places the area characterized by lineage-specific sensitivity to DNase I in a separate chromatin loop.

Conclusions

Taken together, our results strongly support the ACH model but show that within a domain of tissue-specific genes, the active status of a promoter does not necessarily correlate with the recruitment of this promoter to the ACH.
Gender differences in association between metabolic syndrome and carotid intima media thickness
Authors: Tabatabaei-Malazy Ozra , Fakhrzadeh Hossein , Sharifi Farshad , Mirarefin Mojde , Badamchizadeh Zohre , Larijani Bagher
Published: September 2012

Background

Metabolic syndrome (Mets) is a cluster of cardiovascular risk factors which can predicts cardiovascular disease (CVD). Carotid intima-media thickness (CIMT) is known as a surrogate measure of subclinical atherosclerosis and predictor of CVD. Although, it has shown the association between Mets and CIMT, this relation regarding sex differences is limited. We aimed to find out whether gender differences in this association.

Methods

In this cross-sectional study, we recorded height, weight, waist circumference (WC), blood pressure, and lipid profiles. We used Mets; defined based on NCEP ATP III definition, and traditional cardiovascular risk factors; age, body mass index (BMI), WC, hyperlipidemia, and hypertension, in multivariate regression models which including;. The CIMT measurement < 0.73 or ≥0.73 mm was considered as low- or high risk to CVD.

Results

Overall, 150 subjects were enrolled to study that their ages were 36–75 years. The 47.3% of them (71 subjects) had Mets. CIMT was increased in Mets group compared non-Mets group (P = 0.001). In logistic regression analysis, a significant association was found between Mets and CIMT in women, but not in men (p = 0.002, and p = 0.364, respectively). After adjustment to age, WC, BMI, hypertension and hyperlipidemia, this association was significant just in women (p = 0.011) independent of WC, BMI, hyperlipidemia and hypertension.

Conclusion

Our data showed that MetS is a stronger risk factor for subclinical atherosclerosis in women than in men. So, we suggest the assessment of CIMT along with definition Mets in middle-aged women could be lead to earlier detection of at risk individuals to CVD.
Performance of low-fold scalar migration for downhole seismic imaging of massive sulfide ore deposits at Norman West, Sudbury, Canada
Authors: Mueller Christof , Bellefleur Gilles , Adam Erick , Perron Gervais , Mah Marko , Snyder Dave
Published: September 2012

The Downhole Seismic Imaging consortium conducted two consecutive vertical seismic profiling surveys in the Norman West mining camp (Sudbury, Canada) in 1998 and 1999. These were aimed toward imaging a massive sulfide ore deposit situated within the footwall of the Sudbury Igneous Complex (SIC). Three-component seismic data were acquired in four boreholes with variable signal-to-noise ratio and poor polarization quality. Consequently, the images suffered from strong azimuthal ambiguity. A strike filter, passing only reflections originating from within the SIC, was applied during migration to enhance interpretability of the images obtained. Migrated images showed structures correlating with the known position of an ore deposit located 1800 m away from one borehole (N40). Diffraction coherency migration enhanced the image of the deposit, and suggested strong seismic scattering from within the footwall of the SIC.
Adherence to treatment guidelines in clinical practice: study of antipsychotic treatment prior to clozapine initiation
Authors: Howes Oliver D. , Vergunst Francis , Gee Siobhan , McGuire Philip , Kapur Shitij , Taylor David
Published: September 2012

Background

Clozapine is the only antipsychotic drug licensed for treatment-resistant schizophrenia but its use is often delayed. Since previous studies, national guidelines on the use of clozapine and other antipsychotics have been disseminated to clinicians.

Aims

To determine the theoretical delay to clozapine initiation and to quantify the prior use of antipsychotic polypharmacy and high-dose antipsychotic treatment.

Method

Clinico-demographic data were extracted from the treatment records of all patients commencing clozapine in our centre between 2006 and 2010.

Results

Complete records were available for 149 patients. The mean theoretical delay in initiating clozapine was 47.7 months (s.d. = 49.7). Before commencing clozapine, antipsychotic polypharmacy and high-dose treatment was evident in 36.2 and 34.2% of patients respectively. Theoretical delay was related to illness duration (β = 0.7, P<0.001) but did not differ by gender or ethnicity.

Conclusions

Substantial delays to clozapine initiation remain and antipsychotic polypharmacy and high doses are commonly used prior to clozapine, despite treatment guidelines.
Crisis plans in a home treatment team before and after a quality improvement programme
Authors: Tan Emily , Higginbotham Andrew , McQueen Lorette , Bhui Kamaldeep
Published: September 2012

Aims and method

To measure the take-up of formal crisis plans in a specialist home treatment team (HTT) serving an ethnically diverse urban population; and to implement a quality improvement programme and measure its impact on crisis plan completion. Two audits were completed of patients before and after the implementation of a quality improvement programme. Descriptive data are shown by ethnic group, by gender, and for people with multiple hospital admissions.

Results

At baseline, 16.7% of patients at high risk of admission had an HTT crisis plan, compared with 26.7% of a comparison group. Only 23.1% of the crisis plans for patients with a history of frequent admission mentioned the prevention of future admissions. Crisis plan completion improved following the quality improvement programme, when 80.0% of discharges had an HTT crisis plan; of these, 73.0% mentioned admission prevention. In the follow-up audit, 22.7% of patients in the multiple admission group had been readmitted to hospital at least once. Crisis plan completion did not appear to differ by ethnic group or gender and did not appear to be related to hospital readmission.

Clinical implications

Crisis plan completion improved with simple practical methods, but completion was unrelated to gender, ethnicity or later readmission.
Attitudes of medical students in Ireland towards psychiatry: comparison of students from 1994 and 2010
Authors: O'Connor K. , O'Loughlin K. , Somers C. , Wilson L. , Pillay D. , Brennan D. , Clarke M. , Guerandel A. , Casey P. , Malone K. , Lane A.
Published: September 2012

Aims and method

We assess and compare: (a) the attitudes of final-year medical students in 2010 to their 1994 counterparts; (b) the attitudes of third-year medical students with those of their final-year colleagues; (c) the impact of two different teaching modules on students' attitudes. All students completing the year 3 psychiatry preclinical module and the final-year clinical clerkship were asked to anonymously complete three well-validated attitudinal questionnaires on the first and final day of their module in psychiatry.

Results

These data indicate that Irish medical students have a positive attitude to psychiatry even prior to the start of their clinical training in psychiatry. This attitude is significantly more positive now than it was in 1994. A positive attitudinal change was brought about only by the final-year psychiatric clerkship. Students who have completed a degree prior to medicine are less likely to express an interest in a career in psychiatry.

Clinical implications

If we are to address the recruitment difficulties in psychiatry we need to look at innovative and specific ways of translating these positive attitudes into careers in psychiatry.