bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sterilizing Activities of Novel Combinations Lacking First- and Second-Line Drugs in a Murine Model of Tuberculosis
Authors: Williams Kathy , Minkowski Austin , Amoabeng Opokua , Peloquin Charles A. , Taylor Dinesh , Andries Koen , Wallis Robert S. , Mdluli Khisimuzi E. , Nuermberger Eric L. 
Published: April 2012

ABSTRACT

Novel oral regimens composed of new drugs with potent activity against
Mycobacterium tuberculosis
and no cross-resistance with existing agents are needed to shorten and simplify treatment for both drug-susceptible and drug-resistant tuberculosis. As part of a continuing effort to evaluate novel drug combinations for treatment-shortening potential in a murine model, we performed two long-term, relapse-based experiments. In the first experiment, several 3- and 4-drug combinations containing new agents currently in phase 2/3 trials (TMC207 [bedaquiline], PA-824 and PNU-100480 [sutezolid], and/or clofazimine) proved superior to the first-line regimen of rifampin, pyrazinamide, and isoniazid. TMC207 plus PNU-100480 was the most effective drug pair. In the second experiment, in which 3- and 4-drug combinations composed of TMC207 and pyrazinamide plus rifapentine, clofazimine, PNU-100480, or both rifapentine and clofazimine were evaluated, the rank order of drugs improving the sterilizing activity of TMC207 and pyrazinamide was as follows: rifapentine plus clofazimine ≥ clofazimine ≥ rifapentine > PNU-100480. The results revealed potential new building blocks for universally active short-course regimens for drug-resistant tuberculosis. The inclusion of pyrazinamide against susceptible isolates may shorten the duration of treatment further.
Association of a Protective Monoclonal IgA with the O Antigen of Salmonella enterica Serovar Typhimurium Impacts Type 3 Secretion and Outer Membrane Integrity
Authors: Forbes Stephen J. , Martinelli Daniel , Hsieh Chyongere , Ault Jeffrey G. , Marko Michael , Mannella Carmen A. , Mantis Nicholas J. 
Published: April 2012

ABSTRACTInvasion of intestinal epithelial cells bySalmonella entericaserovar Typhimurium is an energetically demanding process, involving the transfer of effector proteins from invading bacteria into host cells via a specialized organelle known as theSalmonellapathogenicity island 1 (SPI-1) type 3 secretion system (T3SS). By a mechanism that remains poorly understood, entry ofS. Typhimurium into epithelial cells is inhibited by Sal4, a monoclonal, polymeric IgA antibody that binds an immunodominant epitope within the O-antigen (O-Ag) component of lipopolysaccharide. In this study, we investigated how the binding of Sal4 to the surface ofS. Typhimurium influences T3SS activity, bacterial energetics, and outer membrane integrity. We found that Sal4 treatment impaired T3SS-mediated translocon formation and attenuated the delivery of tagged effector proteins into epithelial cells. Sal4 treatment coincided with a partial reduction in membrane energetics and intracellular ATP levels, possibly explaining the impairment in T3SS activity. Sal4's effects on bacterial secretion and energetics occurred concurrently with an increase in O-Ag levels in culture supernatants, alterations in outer membrane permeability, and changes in surface ultrastructure, as revealed by transmission electron microscopy and cryo-electron microscopy. We propose that Sal4, by virtue of its ability to bind and cross-link the O-Ag, induces a form of outer membrane stress that compromises the integrity of theS. Typhimurium cell envelope and temporarily renders the bacterium avirulent.
Ingested Human Insulin Inhibits the Mosquito NF-κB-Dependent Immune Response to Plasmodium falciparum
Authors: Pakpour Nazzy , Corby-Harris Vanessa , Green Gabriel P. , Smithers Hannah M. , Cheung Kong W. , Riehle Michael A. , Luckhart Shirley 
Published: April 2012

ABSTRACT

We showed previously that ingested human insulin activates the insulin/IGF-1 signaling pathway in
Anopheles stephensi
and increases the susceptibility of these mosquitoes to
Plasmodium falciparum
. In other organisms, insulin can alter immune responsiveness through regulation of NF-κB transcription factors, critical elements for innate immunity that are also central to mosquito immunity. We show here that insulin signaling decreased expression of NF-κB-regulated immune genes in mosquito cells stimulated with either bacterial or malarial soluble products. Further, human insulin suppressed mosquito immunity through sustained phosphatidylinositol 3-kinase activation, since inhibition of this pathway led to decreased parasite development in the mosquito. Together, these data demonstrate that activation of the insulin/IGF-1 signaling pathway by ingested human insulin can alter NF-κB-dependent immunity, and ultimately the susceptibility, of mosquitoes to
P. falciparum
.
The value of the CHA2DS2-VASc score for refining stroke risk stratification in patients with atrial fibrillation with a CHADS2 score 0–1: A nationwide cohort study
Authors: Olesen Jonas , Torp-Pedersen Christian , Hansen Morten , Lip Gregory 
Published: April 2012

SummaryNorth American and European guidelines on atrial fibrillation (AF) are conflicting regarding the classification of patients at low/intermediate risk of stroke. We aimed to investigate if the CHA2DS2-VASc score improved risk stratification of AF patients with a CHADS2 score of 0–1. Using individual-level-linkage of nationwide Danish registries 1997–2008, we identified patients discharged with AF having a CHADS2 score of 0–1 and not treated with vitamin K antagonist or heparin. In patients with a CHADS2 score of 0, 1, and 0–1, rates of stroke/ thromboembolism were determined according to CHA2DS2-VASc score, and the risk associated with increasing CHA2DS2-VASc score was estimated in Cox regression models adjusted for year of inclusion and anti-platelet therapy. The value of adding the extra CHA2DS2-VASc risk factors to the CHADS2 score was evaluated by c-statistics, Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI). We included 47,576 patients with a CHADS2 score of 0–1, from these 7,536 (15.8%) were CHA2DS2-VASc score=0, 10,062 (21.2%) were CHA2DS2-VASc score=1, 14,310 (30.1%) were CHA2DS2-VASc score=2, 14,188 (29.8%) were CHA2DS2-VASc score=3, and 1,480 (3.1%) were CHA2DS2-VASc score=4. Of the cohort with a CHADS2 score of 0–1, the stroke/thromboembolism rate per 100 person-years increased with increasing CHA2DS2-VASc score (95% confidence interval): 0.84 (0.65–1.08), 1.79 (1.53–2.09), 3.67 (3.34–4.03), 5.75 (5.33–6.21), and 8.18 (6.68–10.02) at one year follow-up with CHA2DS2-VASc scores of 0, 1, 2, 3, and 4, respectively. Patients with a CHADS2 score=0 were not all ‘low risk’, with one-year event rates ranging from 0.84 (CHA2DS2-VASc score=0) to 3.2 (CHA2DS2-VASc score=3). Results from Cox regression analyses, NRI, and IDI confirmed the improved predictive ability of the CHA2DS2-VASc score in the AF patients who have a CHADS2 score of 0–1. In conclusion, the CHA2DS2-VASc provides critical information on risk of stroke in AF patients with a CHADS2 score of 0–1 that can aid a decision of using anti-coagulation. Even in patients categorised as ‘low risk’ using a CHADS2 score=0, the CHA2DS2-VASc score significantly improved the predictive value of the CHADS2 score alone and a CHA2DS2-VASc score=0 could clearly identify ‘truly low risk’ subjects. Use of the CHA2DS2-VASc score would significantly improve classification of AF patients at low and intermediate risk of stroke, compared to the commonly used CHADS2 score.Note: The editorial process for this article was fully handled by Prof. Christian Weber, Editor-in-Chief.
A Diet Rich in Unsaturated Fatty Acids Prevents Progression Toward Heart Failure in a Rabbit Model of Pressure and Volume Overload
Authors: Den Ruijter Hester M. , Verkerk Arie O. , Schumacher Cees A. , Houten Sander M. , Belterman Charly N.W. , Baartscheer Antonius , Brouwer Ingeborg A. , van Bilsen Marc , de Roos Baukje , Coronel Ruben 
Published: April 2012

Background—
During heart failure (HF), cardiac metabolic substrate preference changes from fatty acid (FA) toward glucose oxidation. This change may cause progression toward heart failure. We hypothesize that a diet rich in FAs may prevent this process, and that dietary ω3-FAs have an added antiarrhythmic effect based on action potential (AP) shortening in animals with HF.

Methods and Results—

Rabbits were fed a diet containing 1.25% (w/w) high oleic sunflower oil (HF-ω9, N=11), 1.25% fish oil (HF-ω3, N=11), or no supplement (HF-control, N=8). Subsequently, HF was induced by volume and pressure overload. After 4 months, HF-parameters were assessed, electrocardiograms were recorded, and blood and ventricular tissue were collected. Myocytes were isolated for patch clamp or intracellular Ca
2+
- recordings to study electrophysiologic remodeling and arrhythmogenesis. Both the HF-ω9 and the HF-ω3 groups had larger myocardial FA oxidation capacity than HF control. The HF-ω3 group had significantly lower mean (± SEM) relative heart and lung weight (3.3±0.13 and 3.2±0.12 g kg
−1
, respectively) than HF control (4.8±0.30 and 4.5±0.23), and shorter QTc intervals (167±2.6 versus 182±6.4). The HF-ω9 also displayed a significantly reduced relative heart weight (3.6±0.26), but had similar QTc (179±4.3) compared with HF control. AP duration in the HF-ω3 group was ≈20% shorter due to increased I
to1
and I
K1
and triggered activity, and Ca
2+
-aftertransients were less than in the HF-ω9 group.

Conclusions—
Dietary unsaturated FAs started prior to induction of HF prevent hypertrophy and HF. In addition, fish oil FAs prevent HF-induced electrophysiologic remodeling and arrhythmias.
Depletion of OLFM4 gene inhibits cell growth and increases sensitization to hydrogen peroxide and tumor necrosis factor-alpha induced-apoptosis in gastric cancer cells
Authors: Liu Rui-hua , Yang Mei-hua , Xiang Hua , Bao Li-ming , Yang Hua-an , Yue Li-wen , Jiang Xue , Ang Na , Wu Li-ya , Huang Yi 
Published: April 2012

Abstract

Background
Human olfactomedin 4 (OLFM4) gene is a secreted glycoprotein more commonly known as the anti-apoptotic molecule GW112. OLFM4 is found to be frequently up-regulated in many types of human tumors including gastric cancer and it was believed to play significant role in the progression of gastric cancer. Although the function of OLFM4 has been indicated in many studies, recent evidence strongly suggests a cell or tissue type-dependent role of OLFM4 in cell growth and apoptosis. The aim of this study is to examine the role of gastric cancer-specific expression of OLFM4 in cell growth and apoptosis resistance.

Methods
OLFM4 expression was eliminated by RNA interference in SGC-7901 and MKN45 cells. Cell proliferation, anchorage-independent growth, cell cycle and apoptosis were characterized in vitro. Tumorigenicity was analyzed in vivo. The apoptosis and caspase-3 activation in response to hydrogen peroxide (H2O2) or tumor necrosis factor-alpha (TNF α) were assessed in the presence or absence of caspase inhibitor Z-VAD-fmk.

Results
The elimination of OLFM4 protein by RNA interference in SGC-7901 and MKN45 cells significantly inhibits tumorigenicity both in vitro and in vivo by induction of cell G1 arrest (all P < 0.01). OLFM4 knockdown did not trigger obvious cell apoptosis but increased H2O2 or TNF α-induced apoptosis and caspase-3 activity (all P < 0.01). Treatment of Z-VAD-fmk attenuated caspase-3 activity and significantly reversed the H2O2 or TNF α-induced apoptosis in OLFM4 knockdown cells (all P < 0.01).

Conclusion
Our study suggests that depletion of OLFM4 significantly inhibits tumorigenicity of the gastric cancer SGC-7901 and MKN45 cells. Blocking OLFM4 expression can sensitize gastric cancer cells to H2O2 or TNF α treatment by increasing caspase-3 dependent apoptosis. A combination strategy based on OLFM4 inhibition and anticancer drugs treatment may provide therapeutic potential in gastric cancer intervention.
The Tat protein of human immunodeficiency virus-1 enhances hepatitis C virus replication through interferon gamma-inducible protein-10
Authors: Qu Jing , Zhang Qi , Li Youxing , Liu Weiyong , Chen Lvxiao , Zhu Ying , Wu Jianguo 
Published: April 2012

AbstractBackgroundCo-infection with human immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV) is associated with faster progression of liver disease and an increase in HCV persistence. However, the mechanism by which HIV-1 accelerates the progression of HCV liver disease remains unknown.ResultsHIV-1/HCV co-infection is associated with increased expression of interferon gamma-induced protein-10 (IP-10) mRNA in peripheral blood mononuclear cells (PBMCs). HCV RNA levels were higher in PBMCs of patients with HIV-1/HCV co-infection than in patients with HCV mono-infection. HIV-1 Tat and IP-10 activated HCV replication in a time-dependent manner, and HIV-1 Tat induced IP-10 production. In addition, the effect of HIV-1 Tat on HCV replication was blocked by anti-IP-10 monoclonal antibody, demonstrating that the effect of HIV-1 Tat on HCV replication depends on IP-10. Taken together, these results suggest that HIV-1 Tat protein activates HCV replication by upregulating IP-10 production.ConclusionsHIV-1/HCV co-infection is associated with increased expression of IP-10 mRNA and replication of HCV RNA. Furthermore, both HIV-1 Tat and IP-10 activate HCV replication. HIV-1 Tat activates HCV replication by upregulating IP-10 production. These results expand our understanding of HIV-1 in HCV replication and the mechanism involved in the regulation of HCV replication mediated by HIV-1 during co-infection.
Effects of pistachios on body weight in Chinese subjects with metabolic syndrome
Authors: Wang Xin , Li Zhaoping , Liu Yanjun , Lv Xiaofeng , Yang Wenying 
Published: April 2012

Abstract

Background
Studies have shown that pistachios can improve blood lipid profiles in subjects with moderate hypercholesterolemia which could reduce the risk of cardiovascular disease. However, there is also a widely perceived view that eating nuts can lead to body weight gain due to their high fat content.

Purpose
To investigate the impact of different dosages of pistachios on body weight, blood pressure, blood lipids, blood glucose and insulin in subjects with metabolic syndrome.

Methods
Ninety subjects with metabolic syndrome (consistent with 2005 International Diabetes Federation metabolic syndrome standard without diabetes) were enrolled in three endocrinology outpatient clinics in Beijing. All subjects received dietary counseling according to the guidelines of the American Heart Association Step I diet. After a 4 week run-in, subjects were randomized to consume either the recommended daily serving of 42 g pistachios (RSG), a higher daily serving of 70 g pistachio (HSG) or no pistachios (DCG) for 12 weeks.

Results
Subjects in all three groups were matched at baseline for BMI: DCG 28.03 ± 4.3; RSG 28.12 ± 3.22; and HSG 28.01 ± 4.51 kg/m2. There were no significant changes in body weight or BMI in any groups during the study nor any change from baseline at any time point in any group. During the entire study, there were no significant differences in waist-to-hip ratio among the groups or any change from baseline in any group (DCG -0.00 ± 0.03, RSG -0.01 ± 0.02 and HSG 0.01 ± 0.04). There were no significant differences detected among groups in triglycerides, fasting glucose and 2 hour postprandial glucose following a 75 gram glucose challenge. Exploratory analyses demonstrated that glucose values 2 h after a 75 gm glucose challenge were significantly lower at week 12 compared with baseline values in the HSG group (-1.13 ± 2.58 mmol/L, p = 0.02), and a similar trend was noted in the RSG group (-0.77 ± 2.07 mmol/L, p = 0.06), while no significant change was seen in the DCG group (-0.15 ± 2.27 mmol/L, p = 0.530). At the end of study, serum triglyceride levels were significantly lower compared with baseline in the RSG group (-0.38 ± 0.79 mmol/L, p = 0.018), but no significant changes were observed in the HSG or DCG groups.

Conclusion
Despite concerns that pistachio nut consumption may promote weight gain, the daily ingestion of either 42 g or 70 g of pistachios for 12 weeks did not lead to weight gain or an increase in waist-to-hip ratio in Chinese subjects with metabolic syndrome. In addition, pistachio consumption may improve the risk factor associated with the metabolic syndrome.
On the equivalence between some kinds of implicit and explicit iterations with applications
Authors: Chang Shih-sen , Kim Jong Kyu , Lee HW Joseph , Chan Chi Kin 
Published: April 2012

Abstract
The purpose of this article is to study the equivalence between some kinds of implicit and explicit iterative approximations. As applications, we utilize our results to study the approximation problems arising in nonexpansive semigroup, variational inclusions and equilibrium problem.
The mechanism of pleural inflammation by long carbon nanotubes: interaction of long fibres with macrophages stimulates them to amplify pro-inflammatory responses in mesothelial cells
Authors: Murphy Fiona A , Schinwald Anja , Poland Craig A , Donaldson Ken 
Published: April 2012

Abstract
Carbon nanotubes (CNT) are high aspect ratio nanoparticles with diameters in the nanometre range but lengths extending up to hundreds of microns. The structural similarities between CNT and asbestos have raised concern that they may pose a similar inhalation hazard. Recently CNT have been shown to elicit a length-dependent, asbestos-like inflammatory response in the pleural cavity of mice, where long fibres caused inflammation but short fibres did not. However the cellular mechanisms governing this response have yet to be elucidated. This study examined the in vitro effects of a range of CNT for their ability to stimulate the release of the acute phase cytokines; IL-1β, TNFα, IL-6 and the chemokine, IL-8 from both Met5a mesothelial cells and THP-1 macrophages. Results showed that direct exposure to CNT resulted in significant cytokine release from the macrophages but not mesothelial cells. This pro-inflammatory response was length dependent but modest and was shown to be a result of frustrated phagocytosis. Furthermore the indirect actions of the CNT were examined by treating the mesothelial cells with conditioned media from CNT-treated macrophages. This resulted in a dramatic amplification of the cytokine release from the mesothelial cells, a response which could be attenuated by inhibition of phagocytosis during the initial macrophage CNT treatments. We therefore hypothesise that long fibres elicit an inflammatory response in the pleural cavity via frustrated phagocytosis in pleural macrophages. The activated macrophages then stimulate an amplified pro-inflammatory cytokine response from the adjacent pleural mesothelial cells. This mechanism for producing a pro-inflammatory environment in the pleural space exposed to long CNT has implications for the general understanding of fibre-related pleural disease and design of safe nanofibres.
Recurrent urethrovesical anastomotic strictures following artificial urinary sphincter implantation: a case report
Authors: Adamakis Ioannis , Tyritzis Stavros I , Vasileiou Ioanna , Katafigiotis Ioannis , Leotsakos Ioannis , Fergadaki Sotiria , Stravodimos Konstantinos G , Constantinides Constantinos A 
Published: April 2012

Abstract

Introduction
The management of an anastomotic stricture after a radical prostatectomy can become a complex and difficult situation when an artificial urinary sphincter precedes the formation of the stricture. The urethral narrowing does not allow the passage of the routinely used urological instruments and no previous reports have suggested alternate approaches.

Case presentation
We present the case of a 68-year-old Greek man diagnosed as having a recurrent anastomotic stricture approximately two years after a radical prostatectomy and three years after the implantation of an artificial urinary sphincter, and propose novel alternate methods of treatment. Our patient was first subjected to stricture incision with the use of a rigid ureteroscope with a holmium:yttrium-aluminium-garnet laser fiber, which was followed by a second successful attempt with the use of a pediatric resectoscope. After a one-year follow-up, our patient is doing well, with no evidence of recurrence.

Conclusions
To the best of our knowledge, this is the first report of the management of recurrent urethral strictures following an artificial urinary sphincter implantation. Minimal invasive techniques with the use of small caliber instruments may offer efficient treatment options, diminishing the danger of urethral corrosion.
High Risk of Symptomatic Cardiac Events in Childhood Cancer Survivors
Authors: van der Pal Helena J. , van Dalen Elvira C. , van Delden Evelien , van Dijk Irma W. , Kok Wouter E. , Geskus Ronald B. , Sieswerda Elske , Oldenburger Foppe , Koning Caro C. , van Leeuwen Flora E. , Caron Huib N. , Kremer Leontien C. 
Published: April 2012

Purpose To evaluate the long-term risk for validated symptomatic cardiac events (CEs) and associated risk factors in childhood cancer survivors (CCSs). Patients and Methods We determined CEs grade 3 or higher: congestive heart failure (CHF), cardiac ischemia, valvular disease, arrhythmia and/or pericarditis (according to Common Terminology Criteria for Adverse Events [CTCAE], version 3.0) in a hospital-based cohort of 1,362 5-year CCSs diagnosed between 1966 and 1996. We calculated both marginal and cause-specific cumulative incidence of CEs and cause-specific cumulative incidence of separate events. We analyzed different risk factors in multivariable Cox regression models. Results Overall, 50 CEs, including 27 cases of CHF, were observed in 42 survivors (at a median attained age of 27.1 years). The 30-year cause-specific cumulative incidence of CEs was significantly increased after treatment with both anthracyclines and cardiac irradiation (12.6%; 95% CI, 4.3% to 20.3%), after anthracyclines (7.3%; 95% CI, 3.8% to 10.7%), and after cardiac irradiation (4.0%; 95% CI, 0.5% to 7.4%) compared with other treatments. In the proportional hazards analyses, anthracycline (dose), cardiac irradiation (dose), combination of these treatments, and congenital heart disease were significantly associated with developing a CE. We demonstrated an exponential relationship between the cumulative anthracycline dose, cardiac irradiation dose, and risk of CE. Conclusion CCSs have a high risk of developing symptomatic CEs at an early age. The most common CE was CHF. Survivors treated with both anthracyclines and radiotherapy have the highest risk; after 30 years, one in eight will develop severe heart disease. The use of potentially cardiotoxic treatments should be reconsidered for high-risk groups, and frequent follow-up for high-risk survivors is needed.