bluuebunny/crossref_metadata_2025 huggingface dataset:
Diastolic dysfunction is associated with an increased risk of contrast-induced nephropathy: a retrospective cohort study
Authors: Koo Hyang Mo , Doh Fa Mee , Ko Kwang Il , Kim Chan Ho , Lee Mi Jung , Oh Hyung Jung , Han Seung Hyeok , Kim Beom Seok , Yoo Tae-Hyun , Kang Shin-Wook , Choi Kyu Hun
Published: July 2013

Background

Contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute kidney injury, and it is associated with poor long-term clinical outcomes. Although systolic heart failure is a well-known risk factor for CIN, no studies have yet evaluated the association between diastolic dysfunction and CIN.

Methods

We conducted a retrospective study of 735 patients who underwent percutaneous transluminal coronary angioplasty (PTCA) and had an echocardiography performed within one month of the procedure at our institute, between January 2009 and December 2010. CIN was defined as an increase of ≥ 0.5 mg/dL or ≥ 25% in serum creatinine level during the 72 hours following PTCA.

Results

CIN occurred in 64 patients (8.7%). Patients with CIN were older, had more comorbidities, and had an intra-aortic balloon pump (IABP) placed more frequently during PTCA than patients without CIN. They showed greater high-sensitivity C-reactive protein (hs-CRP) levels and lower estimated glomerular filtration rates (eGFR). Echocardiographic findings revealed lower ejection fraction and higher left atrial volume index and E/E’ in the CIN group compared with non-CIN group. When patients were classified into 3 groups according to the E/E’ values of 8 and 15, CIN occurred in 42 (21.6%) patients in the highest tertile compared with 20 (4.0%) in the middle and 2 (4.3%) in the lowest tertile (p < 0.001). In multivariate logistic regression analysis, E/E’ > 15 was identified as an independent risk factor for the development of CIN after adjustment for age, diabetes, dose of contrast media, IABP use, eGFR, hs-CRP, and echocardiographic parameters [odds ratio (OR) 2.579, 95% confidence interval (CI) 1.082-5.964, p = 0.035]. In addition, the area under the receiver operating characteristic curve of E/E’ was 0.751 (95% CI 0.684-0.819, p < 0.001), which was comparable to that of ejection fraction and left atrial volume index (0.739 and 0.656, respectively, p < 0.001).

Conclusions

This study demonstrated that, among echocardiographic variables, E/E' was an independent predictor of CIN. This in turn suggests that diastolic dysfunction may be a useful parameter in CIN risk stratification.
What price quitting? The price of cigarettes at which smokers say they would seriously consider trying to quit
Authors: Scollo Michelle , Hayes Linda , Wakefield Melanie
Published: July 2013

Background

Deciding on an appropriate level for taxes on tobacco products is a critical issue in tobacco control. The aim of the present study was to describe the critical price points for packs for smokers of each pack size, to calculate what this would equate to in terms of price per stick, and to ascertain whether price points varied by age, socio-economic status and heaviness of smoking.

Methods

In November 2011, 586 Victorian smokers of factory-made cigarettes were asked during a telephone survey about their usual brand, including the size and cost of their usual pack. They were also asked about use of illicit tobacco. Smokers estimated what price their preferred pack would need to reach before they would seriously consider quitting.

Results

Three-quarters of regular smokers of manufactured cigarettes could envisage their usual brand reaching a price at which they would seriously consider quitting. Analyses revealed that answers clustered around whole numbers, (AUD$15, $20, $25 and $30), with a median nominated price point of AUD$20 per pack. The median price point at which regular smokers would consider quitting was calculated to be 80 cents per stick, compared to the current median reported stick price of 60 cents.

Of the smokers who nominated a price point, 60.1% indicated they would seriously consider quitting if the cost of their usual brand equated to 80 cents per stick or less; 87.5% would seriously consider quitting if sticks reached one dollar each.

Conclusions

These results do suggest a potentially useful approach to setting taxes in Australia. If taxes can be set high enough to ensure that the cost of the smokers’ preferred packs exceeds critical price points, then it seems likely that more people would seriously attempt to quit than if the price increased to a level even slightly below the price points. Our study suggests that a tax increase large enough to ensure that a typical pack of 25 cigarettes in Australia cost at least AUD$20 would prompt more than 60% of smokers able to nominate a price point to seriously think about quitting, with particularly strong effects among low-SES smokers.
Effects of FTO RS9939906 and MC4R RS17782313 on obesity, type 2 diabetes mellitus and blood pressure in patients with hypertension
Authors: Marcadenti Aline , Fuchs Flavio D , Matte Ursula , Sperb Fernanda , Moreira Leila B , Fuchs Sandra C
Published: July 2013

Background

Genetic variants of the FTO gene rs9939609 A/T and the MC4R gene rs17782313 C/T have been associated with obesity. Individuals with mutations in MC4R gene have lower blood pressure (BP), independently of obesity. This study aimed to investigate the association of FTO rs9939609 and MC4R rs17782313 with anthropometric indexes, BP, and type 2 diabetes mellitus among hypertensive patients.

Methods

We genotyped 217 individuals (86 men and 131 women) with hypertension (systolic or diastolic BP ≥ 140/90 mmHg or using antihypertensive drugs). Diabetes mellitus was diagnosed according to the American Diabetes Association criteria. Waist and neck circumferences (cm), Body Adiposity Index (BAI,%), Lipid Accumulation Product Index (LAP, cm.mmol.l) and body mass index (BMI, kg/m2) were analyzed using analysis of covariance or modified Poisson’s regression.

Results

Rare allele frequencies were 0.40 for A for FTO rs9939609 and 0.18 for C for MC4R rs17782313. A positive association of FTO rs9939609 and MC4R rs17782313 with BMI was observed in the overall sample. Among men and women, neck circumference was associated with the FTO genotype and, for women, MC4R genotype. In contrast, in men we found a negative association of MC4R rs17782313 with diastolic BP (TT 90.1 ±12.2, TC/CC 83.2 ±12.1; P = 0.03) and borderline association for systolic BP after controlling for age and BMI.

Conclusions

Common genetic variants of FTO rs9939609 have positive associations with BMI and neck circumference and MC4R rs17782313 in women, but a negative association with diastolic and mean blood pressure in men with hypertension.
Relationship between Vitamin D Receptor gene polymorphisms and the components of metabolic syndrome
Authors: Schuch Natielen Jacques , Garcia Vivian Cristina , Vívolo Sandra Roberta Gouvea Ferreira , Martini Lígia Araújo
Published: July 2013

Background

The Vitamin D Receptor gene (VDR) is expressed in many tissues and modulates the expression of several other genes. The purpose of this study was to investigate the association between metabolic syndrome (MetSyn) with the presence of VDR 2228570 C > T and VDR 1544410 A > G polymorphisms in Brazilian adults.

Methods

Two hundred forty three (243) individuals were included in a cross-sectional study. MetSyn was classified using the criteria proposed by National Cholesterol Educational Program - Adult Treatment Panel III. Insulin resistance and β cell secretion were estimated by the mathematical models of HOMA IR and β, respectively. The VDR 2228570 C > T and VDR 1544410 A > G polymorphisms were detected by enzymatic digestion and confirmed by allele specific PCR or amplification of refractory mutation.

Results

Individuals with MetSyn and heterozygosis for VDR 2228570 C > T have higher concentrations of iPTH and HOMA β than those without this polymorphism, and subjects with recessive homozygosis for the same polymorphisms presented higher insulin resistance than those with the heterozygous genotype. There is no association among VDR 1544410 A > G and components of MetSyn, HOMA IR and β, serum vitamin D (25(OH)D3) and intact parathormone (iPTH) levels in patients with MetSyn. A significant lower concentration of 25(OH)D3 was observed only in individuals without MetSyn in the VDR 1544410 A > G genotype. Additionally, individuals without MetSyn and heterozygosis for VDR 2228570 C > T presented higher concentration of triglycerides and lower HDL than those without this polymorphism.

Conclusions

Using two common VDR polymorphism data suggests they may influence insulin secretion, insulin resistance an serum HDL-cholesterol in our highly heterogeneous population. Whether VDR polymorphism may influence the severity of MetSyn component disorder, warrants examination in larger cohorts used for genome-wide association studies.
The evolution of malignant and reactive γδ + T cell clones in a relapse T-ALL case after allogeneic stem cell transplantation
Authors: Chen Shaohua , Huang Xin , Zheng Haitao , Geng Suxia , Wu Xiuli , Yang Lijian , Weng Jianyu , Du Xin , Li Yangqiu
Published: July 2013

Background

To improve the outcome of patients with T-cell acute lymphoblastic leukemia (T-ALL), characterization of the biological features of T-ALL blast cells and the immune status of patients with T-ALL is needed to identify specific therapeutic strategies.

Findings

Using a novel approach based on the combination of fine-tiling comparative genomic hybridization (FT-CGH) and ligation-mediated PCR (LM-PCR), we molecularly identified a malignant γδ + T cell clone with a Vδ5Dδ2Jδ1 rearrangement that was paired with a T cell receptor (TCR) VγI and comprised a Vγ1Vδ5 T cell clone in a relapse T-ALL patient. This malignant Vδ5 T cell clone disappeared after chemotherapy, but the clone was detected again when disease relapsed post allogeneic hematopoietic stem cell transplantation (allo-HSCT) at 100 weeks. Using PCR and GeneScan analyses, the distribution and clonality of the TCR Vγ and Vδ subfamilies were examined before and after allo-HSCT in the patient. A reactive T cell clone with a Vδ4Dδ3Jδ1 rearrangement was identified in all samples taken at different time points (i.e., 4, 8, 68, 100 and 108 weeks after allo-HSCT). The expression of this Vδ4+ T cell clone was higher in the patient during complete remission (CR) post allo-HSCT and at disease relapse.

Conclusions

This study established a sensitive methodology to detect T cell subclones, which may be used to monitor minimal residual disease and immune reconstitution.
Temporo-spatial expression of adrenomedullin and its receptors in the bovine placenta
Authors: Hayashi Ken-Go , Hosoe Misa , Sakumoto Ryosuke , Takahashi Toru
Published: July 2013

Background

Adrenomedullin (AM) is a potent vasodilator peptide and is also involved in various physiological activities. In humans and rodents, AM is found in the uteroplacental unit and may be responsible for fetal development and maintenance of placental function. This study investigated 1) the mRNA expression patterns of AM and its receptor components (calcitonin receptor-like receptor (CRLR), receptor activity modifying protein (RAMP) 2 and RAMP3) during pregnancy and 2) mRNA and protein localization of AM, CRLR and RAMPs in the bovine placentome.

Methods

For real-time quantitative RT-PCR, bovine uteroplacental tissues were collected from Day 25, 60, 100, 150, 200 and 250 of gestation and separated into uterine caruncle (CAR), intercaruncular endometrium (ICAR), extra-embryonic membranes on Day 25 and cotyledonary villous after Day 60 (EEM-COT) and intercotyledonary chorion (ICOT). In situ hybridization and immunohistochemistry was performed to investigate the cellular localization of mRNA and protein of AM, CRLR, RAMP2 and RAMP3 in the placentome on Day 56, 150 and 230 of gestation and interplacentomal tissues on Day 56 of gestation.

Results

AM mRNA was highly expressed on Day 200 in EEM-COT, CAR and ICAR. CRLR mRNA was highly expressed on Day 60 in all portions. RAMP2 mRNA was also highly expressed on Day 60 in ICOT and ICAR. In EEM-COT, mRNA expression of CRLR and RAMP2 decreased from Day 150 to 250. RAMP3 mRNA was highly expressed on Day 150 in EEM-COT, ICOT and ICAR. A distinct AM mRNA and protein signal were only found in trophoblast binucleate cells (BNCs), whereas those of CRLR, RAMP2 and RAMP3 were detected in cotyledonary villous and caruncular epithelial cells. In interplacentomal tissues, AM was detected in BNCs of fetal membrane and a small part of luminal epithelium, endothelial lineage of blood vessels and glandular epithelium of the endometrium. Distinct signals of CRLR, RAMP2 and RAMP3 were found in trophoblast cells, luminal epithelium, stroma under the epithelium, endothelial lineage of blood vessels and glandular epithelium.

Conclusions

Our results indicate that the AM system in the bovine uteroplacental unit may be activated at placentation and transition from the mid to late gestation period. Locally produced AM in the BNCs may play a crucial role in regulation of placental vascular and cellular functions during pregnancy.
Preparation of hierarchical mesoporous CaCO3 by a facile binary solvent approach as anticancer drug carrier for etoposide
Authors: Peng Haibao , Li Kun , Wang Ting , Wang Jin , Wang Jiao , Zhu Rongrong , Sun Dongmei , Wang Shilong
Published: July 2013

To develop a nontoxic system for targeting therapy, a new highly ordered hierarchical mesoporous calcium carbonate nanospheres (CCNSs) as small drug carriers has been synthesized by a mild and facile binary solvent approach under the normal temperature and pressure. The hierarchical structure by multistage self-assembled strategy was confirmed by TEM and SEM, and a possible formation process was proposed. Due to the large fraction of voids inside the nanospheres which provides space for physical absorption, the CCNSs can stably encapsulate the anticancer drug etoposide with the drug loading efficiency as high as 39.7 wt.%, and etoposide-loaded CCNS (ECCNS) nanoparticles can dispersed well in the cell culture. Besides, the drug release behavior investigated at three different pH values showed that the release of etoposide from CCNSs was pH-sensitive. MTT assay showed that compared with free etoposide, ECCNSs exhibited a higher cell inhibition ratio against SGC-7901 cells and also decreased the toxicity of etoposide to HEK 293 T cells. The CLSM image showed that ECCNSs exhibited a high efficiency of intracellular delivery, especially in nuclear invasion. The apoptosis test revealed that etoposide entrapped in CCNSs could enhance the delivery efficiencies of drug to achieve an improved inhibition effect on cell growth. These results clearly implied that the CCNSs are a promising drug delivery system for etoposide in cancer therapy.
A mechanism for detecting dishonest recommendation in indirect trust computation
Authors: Iltaf Naima , Ghafoor Abdul , Zia Uzman
Published: July 2013

Indirect trust computation based on recommendations form an important component in trust-based access control models for pervasive environment. It can provide the service provider the confidence to interact with unknown service requesters. However, recommendation-based indirect trust computation is vulnerable to various types of attacks. This paper proposes a defense mechanism for filtering out dishonest recommendations based on a measure of dissimilarity function between the two subsets. A subset of recommendations with the highest measure of dissimilarity is considered as a set of dishonest recommendations. To analyze the effectiveness of the proposed approach, we have simulated three inherent attack scenarios for recommendation models (bad mouthing, ballot stuffing, and random opinion attack). The simulation results show that the proposed approach can effectively filter out the dishonest recommendations based on the majority rule. A comparison between the exiting schemes and our proposed approach is also given.
Adaptive almost surely asymptotically synchronization for stochastic delayed neural networks with Markovian switching
Authors: Ding Xiangwu , Gao Yan , Zhou Wuneng , Tong Dongbing , Su Hongye
Published: July 2013

In this paper, the problem of the adaptive almost surely asymptotically synchronization for stochastic delayed neural networks with Markovian switching is considered. By utilizing a new nonnegative function and the M-matrix approach, we derive a sufficient condition to ensure adaptive almost surely asymptotically synchronization for stochastic delayed neural networks. Some appropriate parameters analysis and update laws are found via the adaptive feedback control techniques. We also present an illustrative numerical example to demonstrate the effectiveness of the M-matrix-based synchronization condition derived in this paper.
Cytokine and chemokine responses to helminth and protozoan parasites and to fungus and mite allergens in neonates, children, adults, and the elderly
Authors: Lechner Christian J , Komander Karl , Hegewald Jana , Huang Xiangsheng , Gantin Richard G , Soboslay Peter T , Agossou Abram , Banla Meba , Köhler Carsten
Published: July 2013

Background

In rural sub-Saharan Africa, endemic populations are often infected concurrently with several intestinal and intravascular helminth and protozoan parasites. A specific, balanced and, to an extent, protective immunity will develop over time in response to repeated parasite encounters, with immune responses initially being poorly adapted and non-protective. The cellular production of pro-inflammatory and regulatory cytokines and chemokines in response to helminth, protozoan antigens and ubiquitous allergens were studied in neonates, children, adults and the elderly.

Results

In children schistosomiasis prevailed (33%) while hookworm andEntamoeba histolytica/E. disparwas found in up to half of adults and the elderly.Mansonella perstansfilariasis was only present in adults (24%) and the elderly (25%). Two or more parasite infections were diagnosed in 41% of children, while such polyparasitism was present in 34% and 38% of adults and the elderly. Cytokine and chemokine production was distinctively inducible by parasite antigens; pro-inflammatory Th2-type cytokine IL-19 was activated byEntamoebaandAscarisantigens, being low in neonates and children while IL-19 production enhanced “stepwise” in adults and elderly. In contrast, highest production of MIP-1delta/CCL15 was present in neonates and children and inducible byEntamoeba-specific antigens only. Adults and the elderly had enhanced regulatory IL-27 cytokine responses, with Th2-type chemokines (MCP-4/CCL13, Eotaxin-2/CCL24) and cytokines (IL-33) being notably inducible by helminth- andEntamoeba-specific antigens and fungus-derived allergens. The lower cellular responsiveness in neonates and children highlighted the development of a parasite-specific cellular response profile in response to repeated episodes of exposure and re-infection.

Conclusions

Following repeated exposure to parasites, and as a consequence of host inability to prevent or eliminate intestinal helminth or protozoa infections, a repertoire of immune responses will evolve with lessened pro-inflammatory and pronounced regulatory cytokines and chemokines; this is required for partial parasite control as well as for preventing inadequate and excessive host tissue and organ damage.
The N-end rule and retroviral infection: no effect on integrase
Authors: Boso Guney , Tasaki Takafumi , Kwon Yong Tae , Somia Nikunj V
Published: July 2013

Background

Integration of double stranded viral DNA is a key step in the retroviral life cycle. Virally encoded enzyme, integrase, plays a central role in this reaction. Mature forms of integrase of several retroviruses (i.e. HIV-1 and MLV) bear conserved destabilizing N-terminal residues of the N-end rule pathway - a ubiquitin dependent proteolytic system in which the N-terminal residue of a protein determines its half life. Substrates of the N-end rule pathway are recognized by E3 ubiquitin ligases called N-recognins. We have previously shown that the inactivation of three of these N-recognins, namely UBR1, UBR2 and UBR4 in mouse embryonic fibroblasts (MEFs) leads to increased stability of ectopically expressed HIV-1 integrase. These findings have prompted us to investigate the involvement of the N-end rule pathway in the HIV-1 life cycle.

Results

The infectivity of HIV-1 but not MLV was decreased in N-recognin deficient cells in which three N-recognins (UBR1, UBR2 and UBR4) were depleted. HIV-1 integrase mutants of N-terminal amino acids (coding for stabilizing or destabilizing residues) were severely impaired in their infectivity in both human and mouse cells. Quantitative PCR analysis revealed that this inhibition was mainly caused by a defect in reverse transcription. The decreased infectivity was independent of the N-end rule since cells deficient in N-recognins were equally refractory to infection by the integrase mutants. MLV integrase mutants showed no difference in their infectivity or intravirion processing of integrase.

Conclusions

The N-end rule pathway impacts the early phase of the HIV-1 life cycle; however this effect is not the result of the direct action of the N-end rule pathway on the viral integrase. The N-terminal amino acid residue of integrase is highly conserved and cannot be altered without causing a substantial decrease in viral infectivity.
Pseudomonas DING proteins as human transcriptional regulators and HIV-1 antagonists
Authors: Suh Andrew , Le Douce Valentin , Rohr Olivier , Schwartz Christian , Scott Ken
Published: July 2013

Background

Anti-HIV-1 therapy depends upon multiple agents that target different phases of the viral replication cycle. Recent reports indicate that plant and human DING proteins are unique in targeting viral gene transcription as the basis of their anti-HIV-1 therapy.

Methods

Two cloned DING genes fromPseudomonaswere transiently expressed in human cells, and effects on NFκB-mediated transcription, HIV-1 transcription, and HIV-1 production were measured.

Results

Both DING proteins elevated NFκB-mediated transcription. In microglial cells, one protein, fromP. aeruginosaPA14, suppressed HIV-1 transcription; the other protein, fromP. fluorescensSBW25, was inactive. The PA14DING protein also reduces HIV-1 production in microglial cells.

Conclusions

Structural differences between the two DING proteins highlight regions of the PA14DING protein essential to the anti-HIV-1 activity, and may guide the design of therapeutic agents.
Virus replicon particle based Chikungunya virus neutralization assay using Gaussia luciferase as readout
Authors: Gläsker Sabine , Lulla Aleksei , Lulla Valeria , Couderc Therese , Drexler Jan Felix , Liljeström Peter , Lecuit Marc , Drosten Christian , Merits Andres , Kümmerer Beate Mareike
Published: July 2013

Background

Chikungunya virus (CHIKV) has been responsible for large epidemic outbreaks causing fever, headache, rash and severe arthralgia. So far, no specific treatment or vaccine is available. As nucleic acid amplification can only be used during the viremic phase of the disease, serological tests like neutralization assays are necessary for CHIKV diagnosis and for determination of the immune status of a patient. Furthermore, neutralization assays represent a useful tool to validate the efficacy of potential vaccines. As CHIKV is a BSL3 agent, neutralization assays with infectious virus need to be performed under BSL3 conditions. Our aim was to develop a neutralization assay based on non-infectious virus replicon particles (VRPs).

Methods

VRPs were produced by cotransfecting baby hamster kidney-21 cells with a CHIKV replicon expressing Gaussia luciferase (Gluc) and two helper RNAs expressing the CHIKV capsid protein or the remaining structural proteins, respectively. The resulting single round infectious particles were used in CHIKV neutralization assays using secreted Gluc as readout.

Results

Upon cotransfection of a CHIKV replicon expressing Gluc and the helper RNAs VRPs could be produced efficiently under optimized conditions at 32°C. Infection with VRPs could be measured via Gluc secreted into the supernatant. The successful use of VRPs in CHIKV neutralization assays was demonstrated using a CHIKV neutralizing monoclonal antibody or sera from CHIKV infected patients. Comparison of VRP based neutralization assays in 24- versus 96-well format using different amounts of VRPs revealed that in the 96-well format a high multiplicity of infection is favored, while in the 24-well format reliable results are also obtained using lower infection rates. Comparison of different readout times revealed that evaluation of the neutralization assay is already possible at the same day of infection.

Conclusions

A VRP based CHIKV neutralization assay using Gluc as readout represents a fast and useful method to determine CHIKV neutralizing antibodies without the need of using infectious CHIKV.
An educational intervention to reduce pain and improve pain management for Malawian people living with HIV/AIDS and their family carers: study protocol for a randomised controlled trial
Authors: Nkhoma Kennedy , Seymour Jane , Arthur Antony
Published: July 2013

Background

Many HIV/AIDS patients experience pain often due to advanced HIV/AIDS infection and side effects of treatment. In sub-Saharan Africa, pain management for people with HIV/AIDS is suboptimal. With survival extended as a direct consequence of improved access to antiretroviral therapy, the prevalence of HIV/AIDS related pain is increasing. As most care is provided at home, the management of pain requires patient and family involvement. Pain education is an important aspect in the management of pain in HIV/AIDS patients. Studies of the effectiveness of pain education interventions for people with HIV/AIDS have been conducted almost exclusively in western countries.

Methods/design

A randomised controlled trial is being conducted at the HIV and palliative care clinics of two public hospitals in Malawi. To be eligible, patient participants must have a diagnosis of HIV/AIDS (stage III or IV). Carer participants must be the individual most involved in the patient’s unpaid care. Eligible participants are randomised to either: (1) a 30-minute face-to-face educational intervention covering pain assessment and management, augmented by a leaflet and follow-up telephone call at two weeks; or (2) usual care. Those allocated to the usual care group receive the educational intervention after follow-up assessments have been conducted (wait-list control group). The primary outcome is pain severity measured by the Brief Pain Inventory. Secondary outcomes are pain interference, patient knowledge of pain management, patient quality of life, carer knowledge of pain management, caregiver motivation and carer quality of life. Follow-up assessments are conducted eight weeks after randomisation by palliative care nurses blind to allocation.

Discussion

This randomised controlled trial conducted in sub-Saharan Africa among people living with HIV/AIDS and their carers will assess whether a pain education intervention is effective in reducing pain and improving pain management, quality of life and carer motivation.

Trial registration

Current Controlled TrialsISRCTN72861423.
Meigs syndrome presenting with axillary vein thrombosis and lymphadenopathy: a case report
Authors: Iyer Ridhima , Chow Jason , El-Bahrawy Mona , Savage Philip
Published: July 2013

Introduction

Meigs syndrome is a rare condition, occurring in less than 1% of ovarian tumors and has the characteristic features of a benign ovarian tumor, ascites and a pleural effusion. We present a case of Meigs syndrome in a young patient presenting initially with an axillary vein thrombosis and local lymphadenopathy.

Case presentation

A 28-year-old Caucasian woman presented with a short history of right arm swelling and shortness of breath as a result of an axillary vein thrombosis and pulmonary embolus.

The initial assessment also demonstrated right axillary and subclavian lymphadenopathy, a pleural effusion, ascites and a large ovarian mass. Serum levels of the tumor markers human chorionic gonadotropin and alpha-fetoprotein were normal and the CA-125 level was only moderately elevated.

The combination of thrombosis, lymphadenopathy and an ovarian mass raised the possibility of a disseminated malignancy potentially an epithelial ovarian cancer, a germ cell tumor or an ovarian sex cord-stromal tumor.

Surgery, performed after a short period of anticoagulation, demonstrated a 13.5cm ovarian cellular fibroma of low malignant potential. Postoperatively the patient made an excellent recovery and the ascites, pleural effusion and lymphadenopathy all resolved promptly.

Conclusions

In Meigs syndrome the classical findings of ascites, pleural effusion in combination with an ovarian mass can mimic disseminated malignancy but resolve spontaneously after surgery. In this current case, the patient also had lymphadenopathy and venous thrombosis, two other findings that are frequently associated with malignancy and was acutely unwell at presentation.

It is unclear if the thrombosis and lymphadenopathy were simply coincidental or shared the same etiology as the ascites and pleural effusion. This case indicates that Meigs syndrome may on occasion present with additional findings that can further mimic disseminated malignancy and may lead to diagnostic uncertainty.
Heterotrophic growth of Neochloris oleoabundans using glucose as a carbon source
Authors: Morales-Sánchez Daniela , Tinoco-Valencia Raunel , Kyndt John , Martinez Alfredo
Published: July 2013

Background

In comparison with phototrophic growth, heterotrophic conditions can significantly increase growth rates, final cell number and cell mass in microalgae cultures. Neochloris oleoabundans is a microalga of biotechnological interest that accumulates lipids under phototrophic and nitrogen-limited conditions. Heterotrophic flask culture experiments were conducted to identify carbon sources that can be metabolized by N. oleoabundans, and bioreactor batch and fed-batch (nitrate pulse additions) cultures supplemented with glucose were performed to study the cellular composition of the microalgae under balanced and high C/N ratios (glucose/nitrate).

Results

N. oleoabundans was able to grow using glucose and cellobiose as sole carbon sources under strict heterotrophic conditions. Under a balanced C/N ratio of 17 and using bioreactor batch cultures containing 3 g/L glucose, a maximal cell mass of 1.72 g/L was found, with protein being the major cell component (44% w/w). A maximal cell mass of 9.2 g/L was obtained using batch cultures at a C/N ratio of 278. Under these conditions, lipid accumulation was promoted (up to 52% w/w) through N-limitation, resulting in high lipid productivity (528.5 mg/L/day). Fed-batch cultures were performed at a C/N ratio of 278 and with nitrate pulse additions. This condition allowed a maximal cell mass of 14.2 g/L to be achieved and switched the metabolism to carbohydrate synthesis (up to 54% of dry weight), mainly in the form of starch. It was found that transmembrane transport under these conditions was dependent on a proton-motive force, indicating that glucose is transported by a symporter.

Conclusions

N. oleoabundans was able to grow under strict heterotrophic culture conditions with glucose or cellobiose as the only carbon source. The glucose used is transported by a symporter system. Batch cultures with a balanced C/N ratio accumulate proteins as the major cellular component; a high C/N ratio significantly increased the dry cell mass and resulted in a high lipid content, and a high cell density was achieved using fed-batch cultures promoting carbohydrate accumulation. These results suggest heterotrophic batch cultures of N. oleoabundans as an alternative for the production of proteins or lipids with simple culture strategies and minimal-mineral media supplemented with glucose.
Stability and change in the distribution of cytospecies of the Simulium damnosum complex (Diptera: Simuliidae) in southern Ghana from 1971 to 2011
Authors: Post Rory J , Cheke Robert A , Boakye Daniel A , Wilson Michael D , Osei-Atweneboana Mike Y , Tetteh-Kumah Anthony , Lamberton Poppy HL , Crainey J Lee , Yaméogo Laurent , Basáñez María-Gloria
Published: July 2013

Background

Simulium damnosum s.l., the most important vector of onchocerciasis in Africa, is a complex of sibling species that have been described on the basis of differences in their larval polytene chromosomes. These (cyto) species differ in their geographical distributions, ecologies and epidemiological roles. In Ghana, distributional changes have been recorded as a consequence of vector control and environmental change (e.g. deforestation), with potential disease consequences. We review the distribution of cytospecies in southern Ghana and report changes observed with reference to historical data collated from 1971 to 2005 and new identifications made between 2006 and 2011.

Methods/Results

Larvae were collected from riverine breeding sites, fixed in Carnoy’s solution and chromosome preparations made. Cytotaxonomic identifications from 1,232 samples (including 49 new samples) were analysed. We report long-term stability in cytospecies distribution in the rivers Afram, Akrum, Pawnpawn and Pru. For the rivers Oda, Ofin and Tano we describe (for the first time) patterns of distribution. We could not detect cytospecies composition changes in the upper Pra, and the lower Pra seems to have been stable. The elimination of the Djodji form of S. sanctipauli in the Volta Region seems to have had no long-term effects on the distribution of the other cytospecies, despite an initial surge by S. yahense. There has been a recent increase in the occurrence of savannah cytospecies in the river Asukawkaw, and this might be related to continuing deforestation.

Conclusions

Cytospecies’ distributions have not been stable from 1971 to 2011. Although there are no obvious causes for the temporary appearance and subsequent disappearance of cytospecies in a particular location, a major influence has been vector control and migration patterns, probably explaining observed changes on the Black Volta and lower Volta rivers. Deforestation was previously implicated in an increase of savannah cytospecies in southern Ghana (1975–1997). Our data had little power to support (or refute) suggestions of a continuing increase, except in the Asukawkaw river basin.
A comparison of the Doppler ultrasound interpretation by student and registered podiatrists
Authors: Young Maria , Birch Ivan , Potter Chloe Alexa , Saunders Robert , Otter Simon , Hussain Shahin , Pellett Jane , Reynolds Nadine , Jenkin Sarah , Wright Wendy
Published: July 2013

Background

Hand held Doppler ultrasound machines are routinely used by podiatrists to assess the arterial perfusion of the lower limb. They are practical, painless and effective as a screening tool, and the available general evidence would suggest that interpretation by practitioners is reliable. This study compared the abilities of student and Health and Care Professions Council (HCPC) registered podiatrists to identify correctly Doppler ultrasound outputs.

Method

A prospective single blind comparative study design was utilised. Fifteen Doppler recordings of the blood flow in the posterior tibial artery, five each of monophasic, biphasic and triphasic blood flow, were used to compare the interpretation abilities of 30 undergraduate podiatry students and 30 HCPC registered podiatrists. Chi‐squared analysis of the results was undertaken.

Results

Chi‐squared analysis found that there was no statistically significant difference between the overall abilities of student podiatrists and HCPC registered podiatrists to identify correctly Doppler ultrasound recordings (p = 0.285). No significant difference was found in their ability to identify Doppler ultrasound recordings of monophasic, biphasic or triphasic blood flow (p > 0.050).

Conclusion

The results of this relatively small study suggest that both student and HCPC registered podiatrists are in general able to identify the nature of blood flow based on the output of handheld Doppler ultrasound units. However, the results raise an issue regarding professional development of practitioners who might have been expected to have enhanced their skills of Doppler ultrasound sound identification since professional registration.
Creation of a Merkel cell polyomavirus small T antigen-expressing murine tumor model and a DNA vaccine targeting small T antigen
Authors: Gomez Bianca , He Liangmei , Tsai Ya Chea , Wu T-C , Viscidi Raphael P , Hung Chien-Fu
Published: July 2013

Background

Merkel cell polyomavirus (MCPyV) is a DNA virus expressing transcripts similar to the large T (LT) and small T (ST) transcripts of SV40, which has been implicated in the pathogenesis of Merkel cell carcinoma (MCC), a rare and highly aggressive neuroendocrine skin cancer. MCPyV LT antigen expression was found to be a requirement for MCC tumor maintenance and ST protein also likely contributes to the carcinogenesis of MCC. Previously, we have identified the probable immunodominant epitope of MCPyV LT and developed a DNA vaccine encoding this epitope linked to calreticulin. The LT-targeting DNA vaccine generated prolonged survival, decreased tumor size and increased LT-specific CD8+ T cells in tumor-bearing mice.

Results

In this study, we developed a MCPyV ST-expressing tumor cell line from B16 mouse melanoma cells. We then utilized this ST-expressing tumor cell line to test the efficacy of a DNA vaccine encoding ST. In ST-expressing tumor-bearing mice, this vaccine, pcDNA3-MCC/ST, generated a significant number of ST antigenic peptide-specific CD8+ T cells and experienced markedly enhanced survival compared to mice vaccinated with empty vector.

Conclusions

The formation of an effective vaccine against MCPyV has the potential to advance the field of MCC therapy and may contribute to the control of this severe malignancy through immunotherapy. Both of the innovative technologies presented here provide opportunities to develop and test MCPyV-targeted therapies for the control of Merkel cell carcinoma.
Simplified programming and control of automated radiosynthesizers through unit operations
Authors: Claggett Shane B , Quinn Kevin M , Lazari Mark , Moore Melissa D , van Dam R Michael
Published: July 2013

Background

Many automated radiosynthesizers for producing positron emission tomography (PET) probes provide a means for the operator to create custom synthesis programs. The programming interfaces are typically designed with the engineer rather than the radiochemist in mind, requiring lengthy programs to be created from sequences of low-level, non-intuitive hardware operations. In some cases, the user is even responsible for adding steps to update the graphical representation of the system. In light of these unnecessarily complex approaches, we have created software to perform radiochemistry on the ELIXYS radiosynthesizer with the goal of being intuitive and easy to use.

Methods

Radiochemists were consulted, and a wide range of radiosyntheses were analyzed to determine a comprehensive set of basic chemistry unit operations. Based around these operations, we created a software control system with a client–server architecture. In an attempt to maximize flexibility, the client software was designed to run on a variety of portable multi-touch devices. The software was used to create programs for the synthesis of several 18F-labeled probes on the ELIXYS radiosynthesizer, with [18F]FDG detailed here. To gauge the user-friendliness of the software, program lengths were compared to those from other systems. A small sample group with no prior radiosynthesizer experience was tasked with creating and running a simple protocol.

Results

The software was successfully used to synthesize several 18F-labeled PET probes, including [18F]FDG, with synthesis times and yields comparable to literature reports. The resulting programs were significantly shorter and easier to debug than programs from other systems. The sample group of naive users created and ran a simple protocol within a couple of hours, revealing a very short learning curve. The client–server architecture provided reliability, enabling continuity of the synthesis run even if the computer running the client software failed. The architecture enabled a single user to control the hardware while others observed the run in progress or created programs for other probes.

Conclusions

We developed a novel unit operation-based software interface to control automated radiosynthesizers that reduced the program length and complexity and also exhibited a short learning curve. The client–server architecture provided robustness and flexibility.
A transgenic Xenopus laevis reporter model to study lymphangiogenesis
Authors: Ny Annelii , Vandevelde Wouter , Hohensinner Philipp , Beerens Manu , Geudens Ilse , Diez-Juan Antonio , Brepoels Katleen , Plaisance Stéphane , Krieg Paul A. , Langenberg Tobias , Vinckier Stefan , Luttun Aernout , Carmeliet Peter , Dewerchin Mieke
Published: July 2013

The importance of the blood- and lymph vessels in the transport of essential fluids, gases, macromolecules and cells in vertebrates warrants optimal insight into the regulatory mechanisms underlying their development. Mouse and zebrafish models of lymphatic development are instrumental for gene discovery and gene characterization but are challenging for certain aspects, e.g. no direct accessibility of embryonic stages, or non-straightforward visualization of early lymphatic sprouting, respectively. We previously demonstrated that the Xenopus tadpole is a valuable model to study the processes of lymphatic development. However, a fluorescent Xenopus reporter directly visualizing the lymph vessels was lacking. Here, we created transgenic Tg(Flk1:eGFP) Xenopus laevis reporter lines expressing green fluorescent protein (GFP) in blood- and lymph vessels driven by the Flk1 (VEGFR-2) promoter. We also established a high-resolution fluorescent dye labeling technique selectively and persistently visualizing lymphatic endothelial cells, even in conditions of impaired lymph vessel formation or drainage function upon silencing of lymphangiogenic factors. Next, we applied the model to dynamically document blood and lymphatic sprouting and patterning of the initially avascular tadpole fin. Furthermore, quantifiable models of spontaneous or induced lymphatic sprouting into the tadpole fin were developed for dynamic analysis of loss-of-function and gain-of-function phenotypes using pharmacologic or genetic manipulation. Together with angiography and lymphangiography to assess functionality, Tg(Flk1:eGFP) reporter tadpoles readily allowed detailed lymphatic phenotyping of live tadpoles by fluorescence microscopy. The Tg(Flk1:eGFP) tadpoles represent a versatile model for functional lymph/angiogenomics and drug screening.
Insights into the osteoblast precursor differentiation towards mature osteoblasts induced by continuous BMP-2 signaling
Authors: Zouani Omar F. , Rami Lila , Lei Yifeng , Durrieu Marie-Christine
Published: July 2013

Mature osteoblasts are the cells responsible for bone formation and are derived from precursor osteoblasts. However, the mechanisms that control this differentiation are poorly understood. In fact, unlike the majority of organs in the body, which are composed of “soft” tissue from which cells can easily be isolated and studied, the “hard” mineralized tissue of bone has made it difficult to study the function of bone cells. Here, we established an in vitro model that mimics this differentiation under physiological conditions. We obtained mature osteoblasts and characterized them on the basis of the following parameters: the strong expression of osteoblastic markers, such as Runx2 and Col-I; the achievement of specific dimensions (the cell volume increases 26-fold compared to the osteoblast precursors); and the production of an abundant extracellular matrix also called osteoid. We demonstrated that the differentiation of osteoblast precursors into mature osteoblasts requires the continuous activation of Bone Morphogenetic Protein (BMP) receptors, which we established with the immobilization of a BMP-2mimetic peptide on a synthetic matrix mimicking in vivo microenvironment. Importantly, we demonstrated that the organization of the F-actin network and acetylated microtubules of the cells were modified during the differentiation process. We showed that the perturbation of the F-actin cytoskeleton organization abolished the differentiation process. In addition, we demonstrated that expression of the Runx2 gene is required for this differentiation. These findings demonstrate the retro-regulation of cytoplasmic and genic components due to the continuous induction of BMP-2 and also provide more detailed insights into the correct signaling of BMPs for cell differentiation in bone tissue.
Fluorescently tagged Lin7c is a dynamic marker for polarity maturation in the zebrafish retinal epithelium
Authors: Luz Marta , Knust Elisabeth
Published: July 2013

Development of epithelial cell polarity is a highly dynamic process, and often established by the sequential recruitment of conserved protein complexes, such as the Par or the Crumbs (Crb) complex. However, detailed insights into the refinement of polarity and the formation of the complexes are still lacking. Here, we established fluorescently tagged Lin7c, a core member of the Crb complex, as an ideal tool to follow development of polarity in zebrafish epithelia. We find that in gastrula stages, RFP-Lin7c is found in the cytosol of the enveloping layer, while Pard3-GFP is already polarized at this stage. During development of the retinal epithelium, RFP-Lin7c localization is refined from being cytosolic at 14 hours post fertilization (hpf) to almost entirely apical in cells of the eye cup at 28 hpf. This apical Lin7c localization depends on the Crb complex members Oko meduzy and Nagie oko. Thus, fluorescently tagged Lin7c can be used in a broad range of epithelia to follow polarity maturation in vivo and specifically to elucidate the sequence of events determining Crb complex-mediated polarity.
Superparamagnetic Core-Shell Polymeric Nanocomposites for Efficient Removal of Methylene Blue from Aqueous Solutions
Authors: Atta Ayman , Akl Magda A , Youssef AbdElfatah M , Ibraheim Mohamed A
Published: July 2013

Ultrafine well-dispersed Fe3O4 magnetic nanoparticles (NPs) were directly prepared in an aqueous solution using controlled co-precipitation method. The Fe3O4-poly(acrylamide-co-sodium acrylate) core-shell magnetic nanogels are prepared by solution polymerization of acrylamide (AM) and sodium acrylate (AA-Na) monomers in the presence of Fe3O4 NPs, N,N′-methylenebisacrylamide (MBA) as a cross-linker, N,N,N′,N′-tetramethylethylenediamine and potassium peroxydisulphate (KPS) as the redox initiator system. The novel Fe3O4-poly(acrylamide-co-sodium acrylate) core-shell magnetic nanocomposite hydrogels are prepared by in situ free radical co-polymerization of AM and AA-Na in an aqueous dispersion of nanogel particles using MBA as the cross-linker and KPS as the initiator. The as-prepared nanocomposite hydrogels are characterized by Fourier transform infrared spectroscopy spectra, X-ray powder diffraction and transmission electron microscopic measurements. The mean particle size of the synthesized magnetite (Fe3O4) NPs was approximately 8 nm. The diameter of the stabilized polymer-coated Fe3O4 nanogels is approximately 11 nm. The surface morphology of the nanocomposites has been studied by scanning electron microscopy and atomic force microscopy. The Fe3O4-poly(acrylamide-co-sodium acrylate) nanocomposites have been extensively investigated for the removal of basic dyes from aqueous solutions. Results of batch experiments showed that these adsorbents exhibited high sorption capacities towards methylene blue (MB). Experimental data were analyzed using first-order kinetics, pseudo-second-order kinetics and intra-particle diffusion models. The kinetics followed a pseudo-second-order equation. Equilibrium isotherm data were analyzed according to Langmuir and Freundlich equations. The thermodynamic parameters for the adsorption of MB onto the nanocomposite hydrogels were also calculated. Regeneration of nanocomposite adsorbents can be easily achieved.