Evaluation of the frequency of left renal vein variations in computed tomography and its relationship with cancer development

Background: Left renal vein (LRV) variations occur in 0.8–10.2% of the population. The most common LRV variations are retroaortic left renal vein (RLRV) and circumaortic left renal vein (CLRV). The purpose of this study is to determine the frequency of LRV variations in a large series on computed tomography (CT) and to investigate the association between LRV and malignancy development.Materials and methods: Between January 2015 and January 2017, an abdominal CT examination of 12,341 (5505 female, 6836 male) patients was evaluated retrospectively in this study. Patients’ clinical and demographic data were recorded using the Hospital Information System.Results: Left renal vein variations were detected in 314 (2.54%) of the 12,341 patients within the study. Of the 314 cases found to have LRV variations, 227 (1.84%) had RLRV, and 87 (0.70%) had CLRV. There was no statistical difference in total LRV variations (p = 0.083) and CLRV variation (p = 0.96) groups in terms of gender. However, the RLRV variation was found to be 1.32 times higher in males than in females (p = 0.039). Of the 314 patients with LRV variations, 73 (23.2%) had any sort of concomitant malignancy.Conclusions: A high incidence of malignancy was detected in patients with LRV variations. Of the LRV variations, RLRV variation is more common than CLRV variation. The presence of total LRV variations and CLRV variations is not associated with gender; whereas the presence of RLRV variation is more common in males

SMALL ENGINE-GENERATOR SET OPERATING ON DUAL-FUEL MODE WITH ETHANOL – CASTOR OIL BLENDS

The increase in greenhouse gas emissions and our dependence on fossil fuels have motivated researchers to seek the use of renewable fuels in internal combustion engines, which can be produced locally and have clean combustion. The blending method in diesel engines has been recognized as an effective alternative to partially or totally replace the use of diesel fuel. In this regard, this paper studied the operation of a small engine-generator set in mono-fuel mode (diesel fuel - DO) and in dual-fuel mode using hydrous ethanol (HET) and castor oil (OM) blends, indicating a total replacement of diesel fuel. Efficiency, power, specific fuel consumption and gaseous emissions were assessed in a single cylinder diesel cycle engine. The percentages in volume of the HET-OM samples were: 75% - 25%, 70% - 30%, 60% - 40%, and 50% - 50%. The exhaust gas temperature decreased with the mixtures. Carbon monoxide emission decreased 57%, carbon dioxide decreased 9.8%, and nitrogen oxides reduced 19%. It was also observed that the percentage of smoke opacity tends to decrease close to zero with addition of ethanol. Hydrocarbon emissions increased with rising of the OM concentration and the same for the specific fuel consumptions, which was 25.4% higher than diesel fuel. The best fuel conversion efficiency was achieved with the blend HET75-OM25, being 9% higher compared to diesel fuel operation. Power on diesel fuel operation showed a better result keeping stable, with the increase of the compression ratio and the delay of the start of injection. In general, the results confirmed that the performance is comparable to that of diesel fuel, indicating that renewable fuels appear as an alternative for the reduction of the environmental impacts and the reduction of fossil fuels consumption

PRELIMINARY STUDY OF WATER INJECTION ON THE COMBUSTION AND EMISSIONS CHARACTERISTICS IN A HCCI ETHANOL ENGINE

Our dependence on fossil fuels coupled with concerns about harmful emissions have motivated researchers to look for renewable fuels that have clean combustion and for advanced combustion modes. In this context, homogeneous charge compression ignition (HCCI) is an emerging technology which offers an alternative to conventional spark ignition and compression ignition engines and can operate on renewable fuels. Low temperature combustion, which can result in low NOx emissions with high indicated efficiency, is the more important characteristic of this combustion mode. It’s main problem is the combustion timing control due to lack of direct ignition control, once HCCI flame initiation is based on charge thermal state. Thus, controlled auto-ignition (CAI) combustion mode has been proposed. Several methods were proposed for combustion phasing control, between them, the injection of water in the intake manifold. This work investigated the influence of water injection in the intake runner of an ethanol HCCI cylinder from a converted three-cylinder diesel generator set, in which two cylinders operated on conventional diesel combustion and one diesel cylinder provided recycled exhaust gas for the one cylinder running on ethanol HCCI combustion. The water injection was used to control the CA50 combustion parameter. The results show that water injection is an efficient strategy to control the combustion timing, since the reactivity of the mixture can be controlled. The results at 400 and 600 kPa of IMEP and 1800 rpm indicated a good combustion stability, high efficiency and low emissions characteristics. The highest indicated fuel conversion efficiency found was 36.9% for 600 kPa of IMEP and 8 CAD of CA50. However, for 200 kPa of IMEP the combustion was unstable, the indicated efficiency was deteriorated and indicted CO emissions was high

DNA adducts in fish following an oil spill exposure

On 12 December 1999, one third of the load of the Erika tanker, amounting to about 10,000 t crude oil flowed into sea waters close to the French Atlantic Coast. This oil contained polycyclic aromatic compounds (PAC) that are known to be genotoxic. Genotoxic effects induce DNA adducts formation, which can thus be used as pollution biomarkers. Here, we assessed the genotoxic impact of the “Erika” oil spill by DNA adducts detection in the liver of immature fishes (Solea solea) from four locations of the French Brittany coasts. Two months after the spill, a high amount of DNA adducts was found in samples from all locations, amounting to 92–290 DNA adduct per 109 nucleotides. Then total DNA adduct levels decreased to reach about 50 adducts per 109 nucleotides nine months after the spill. In vitro experiments using human cell cultures and fish liver microsomes evidence the genotoxicity of the Erika fuel. They also prove the formation of reactive species able to create DNA adducts. Furthermore, in vitro and in vivo DNA adducts fingerprints are similar, thus confirming that DNA adducts are a result of the oil spill

Ongoing under-reporting of clinically relevant safety data in phase II studies of tyrosine kinase inhibitors

status: publishe

Synchronization of Circadian Clock Gene Expression in Arabidopsis and Hyaloperonospora arabidopsidis and its Impact on Host-Pathogen Interactions

Organisms across all kingdoms have an internal circadian clock running in 24h cycles. This clock affects a variety of processes, including innate immunity in plants. However, the role of pathogen circadian clocks had not been extensively explored. We previously showed that light can influence infection of the oomycete Hyaloperonospora arabidopsidis (Hpa, downy mildew disease) on its natural host Arabidopsis thaliana. Here, we identified Hpa orthologs of known circadian clock genes (CCGs) Drosophila TIMELESS (TIM) and Arabidopsis Sensitive to Red Light Reduced 1 (AtSRR1) genes. Expression of both HpaTIM and HpaSRR1 showed a circadian rhythm when Hpa was exposed to constant light. Contrastingly, these two genes were negatively regulated by constant dark exposure. Furthermore, the expression patterns of HpaTIM and HpaSRR1 correlate with those of AtCCA1 and AtLHY, indicating a synchronisation of biological clock genes between the host and the pathogen. In addition, screening mutants of Arabidopsis Clock Regulated Genes (AtCRGs) with three virulent Hpa isolates revealed that mutations in AtCRGs influenced HpaTIM and HpaSRR1 expression and Hpa development, indicating a functional link between the plant biological clock and virulence. Moreover, sporulation of Hpa was reduced by targeting HpaTIM and HpaSRR1 with short synthesized small interfering RNAs, indicating that the pathogen clock is also relevant to virulence. We propose that plant and pathogen clocks are synchronized during infection and that proper regulation of both clocks are genetically necessary for pathogen virulence

A phase I open-label study evaluating the cardiovascular safety of sorafenib in patients with advanced cancer

Purpose: To characterize the cardiovascular profile of sorafenib, a multitargeted kinase inhibitor, in patients with advanced cancer. Methods: Fifty-three patients with advanced cancer received oral sorafenib 400 mg bid in continuous 28-day cycles in this open-label study. Left ventricular ejection fraction (LVEF) was evaluated using multigated acquisition scanning at baseline and after 2 and 4 cycles of sorafenib. QT/QTc interval on the electrocardiograph (ECG) was measured in triplicate with a Holter 12-lead ECG at baseline and after 1 cycle of sorafenib. Heart rate (HR) and blood pressure (BP) were obtained in duplicate at baseline and after 1 and 4 cycles of sorafenib. Plasma pharmacokinetic data were obtained for sorafenib and its 3 main metabolites after 1 and 4 cycles of sorafenib. Results: LVEF (SD) mean change from baseline was -0.8 ($\pm$8.6) LVEF(%) after 2 cycles (n=31) and -1.2 $\pm$7.8) LVEF(%) after 4 cycles of sorafenib (n=24). The QT/QTc mean changes from baseline observed at maximum sorafenib concentrations ($t_{max}$) after 1 cycle (n=31) were small (QTcB: 4.2 ms; QTcF: 9.0 ms). Mean changes observed after 1 cycle in BP (n=31) and HR (n=30) at maximum sorafenib concentrations ($t_{max}$) were moderate (up to 11.7 mm Hg and -6.6 bpm, respectively). No correlation was found between the AUC and ($C_{max}$) of sorafenib and its main metabolites and any cardiovascular parameters. Conclusions: The effects of sorafenib on changes in QT/QTc interval on the ECG, LVEF, BP, and HR were modest and unlikely to be of clinical significance in the setting of advanced cancer treatment

Rationale and design of the Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research Trial (MANTICORE 101 - Breast): a randomized, placebo-controlled trial to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer using cardiac MRI

<p>Abstract</p> <p>Background</p> <p>MANTICORE 101 - Breast (Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research) is a randomized trial to determine if conventional heart failure pharmacotherapy (angiotensin converting enzyme inhibitor or beta-blocker) can prevent trastuzumab-mediated left ventricular remodeling, measured with cardiac MRI, among patients with HER2+ early breast cancer.</p> <p>Methods/Design</p> <p>One hundred and fifty-nine patients with histologically confirmed HER2+ breast cancer will be enrolled in a parallel 3-arm, randomized, placebo controlled, double-blind design. After baseline assessments, participants will be randomized in a 1:1:1 ratio to an angiotensin-converting enzyme inhibitor (perindopril), beta-blocker (bisoprolol), or placebo. Participants will receive drug or placebo for 1 year beginning 7 days before trastuzumab therapy. Dosages for all groups will be systematically up-titrated, as tolerated, at 1 week intervals for a total of 3 weeks. The primary objective of this randomized clinical trial is to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer, as measured by 12 month change in left ventricular end-diastolic volume using cardiac MRI. Secondary objectives include 1) determine the evolution of left ventricular remodeling on cardiac MRI in patients with HER2+ early breast cancer, 2) understand the mechanism of trastuzumab mediated cardiac toxicity by assessing for the presence of myocardial injury and apoptosis on serum biomarkers and cardiac MRI, and 3) correlate cardiac biomarkers of myocyte injury and extra-cellular matrix remodeling with left ventricular remodeling on cardiac MRI in patients with HER2+ early breast cancer.</p> <p>Discussion</p> <p>Cardiac toxicity as a result of cancer therapies is now recognized as a significant health problem of increasing prevalence. To our knowledge, MANTICORE will be the first randomized trial testing proven heart failure pharmacotherapy in the prevention of trastuzumab-mediated cardiotoxicity. We expect the findings of this trial to provide important evidence in the development of guidelines for preventive therapy.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01016886">NCT01016886</a></p