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

PAH/PCB CONCENTRATIONS IN MUSSELS (MYTILUS GALLOPROVINCIALIS) FROM IZMIT BAY

Abstract PAH and PCB concentrations were determined in mussel samples collected from Izmit Bay at the east of marmara Sea. The samples were taken from ten points in spring season and analyzed by gas chromatography after ultrasonic extraction. Total PAH concentrations varied between 2.5-13.9 ng.g-wet wt., while the total PCB concentrations were between 4.2-140.7 ng.g-wet wt. The results indicates a considerable pollution problem in the bay, especially with respect to PCBs

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

The Early Social Cognition Inventory (ESCI): an examination of its psychometric properties from birth to 47 months

Social cognition refers to a broad range of cognitive processes and skills that allow individuals to interact with and understand others, including a variety of skills from infancy through preschool and beyond, e.g., joint attention, imitation, and belief understanding. However, no measures examine socio-cognitive development from birth through preschool. Current test batteries and parent-report measures focus either on infancy, or toddlerhood through preschool (and beyond). We report six studies in which we developed and tested a new 21-item parent-report measure of social cognition targeting 0–47 months: the Early Social Cognition Inventory (ESCI). Study 1 (N = 295) revealed the ESCI has excellent internal reliability, and a two-factor structure capturing social cognition and age. Study 2 (N = 605) also showed excellent internal reliability and confirmed the two-factor structure. Study 3 (N = 84) found a medium correlation between the ESCI and a researcher-administered social cognition task battery. Study 4 (N = 46) found strong 1-month test–retest reliability. Study 5 found longitudinal stability (6 months: N = 140; 12 months: N = 39), and inter-observer reliability between parents (N = 36) was good, and children’s scores increased significantly over 6 and 12 months. Study 6 showed the ESCI was internally reliable within countries (Australia, Canada, United Kingdom, United States, Trinidad and Tobago); parent ethnicity; parent education; and age groups from 4–39 months. ESCI scores positively correlated with household income (UK); children with siblings had higher scores; and Australian parents reported lower scores than American, British, and Canadian parents

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

Higher Absolute Lymphocyte Counts Predict Lower Mortality from Early-Stage Triple-Negative Breast Cancer

Purpose: Tumor-infiltrating lymphocytes (TIL) in pretreatment biopsies are associated with improved survival in triple-negative breast cancer (TNBC). We investigated whether higher peripheral lymphocyte counts are associated with lower breast cancer–specific mortality (BCM) and overall mortality (OM) in TNBC. Experimental Design: Data on treatments and diagnostic tests from electronic medical records of two health care systems were linked with demographic, clinical, pathologic, and mortality data from the California Cancer Registry. Multivariable regression models adjusted for age, race/ethnicity, socioeconomic status, cancer stage, grade, neoadjuvant/adjuvant chemotherapy use, radiotherapy use, and germline BRCA1/2 mutations were used to evaluate associations between absolute lymphocyte count (ALC), BCM, and OM. For a subgroup with TIL data available, we explored the relationship between TILs and peripheral lymphocyte counts. Results: A total of 1,463 stage I–III TNBC patients were diagnosed from 2000 to 2014; 1,113 (76%) received neoadjuvant/adjuvant chemotherapy within 1 year of diagnosis. Of 759 patients with available ALC data, 481 (63.4%) were ever lymphopenic (minimum ALC <1.0 K/μL). On multivariable analysis, higher minimum ALC, but not absolute neutrophil count, predicted lower OM [HR = 0.23; 95% confidence interval (CI), 0.16–0.35] and BCM (HR = 0.19; CI, 0.11–0.34). Five-year probability of BCM was 15% for patients who were ever lymphopenic versus 4% for those who were not. An exploratory analysis (n = 70) showed a significant association between TILs and higher peripheral lymphocyte counts during neoadjuvant chemotherapy. Conclusions: Higher peripheral lymphocyte counts predicted lower mortality from early-stage, potentially curable TNBC, suggesting that immune function may enhance the effectiveness of early TNBC treatment

Ethanol production from xylose by pichia stipitis NRRL Y-7124 in a stirred tank bioreactor

The ethanol production by Pichia stipitis was evaluated in a stirred tank bioreactor using semidefined medium containing xylose (90.0 g/l) as the main carbon source. Experimental assays were performed according to a 22 full factorial design to evaluate the influence of aeration (0.25 to 0.75 vvm) and agitation (150 to 250 rpm) conditions on ethanol production. In the studied range of values, the agitation increase and aeration decrease favored ethanol production, which was maximum (26.7 g/l) using 250 rpm and 0.25 vvm, conditions that gave a volumetric oxygen transfer coefficient (kLa value) of 4.9 h-1. Under these conditions, the ethanol yield factor, ethanol productivity, and the process efficiency were 0.32 g/g, 0.32 g/l.h, and 63%, respectively. These results are promising and contribute to the development of a suitable process for ethanol production from xylose by Pichia stipitis.The authors gratefully acknowledge Santander, Fapesp, Capes, and CNPq (Brazil)

The novel KV7 channel activator URO-K10 exerts enhanced pulmonary vascular effects independent of the KCNE4 regulatory subunit.

KV7 channels exert a pivotal role regulating vascular tone in several vascular beds. In this context, KV7 channel agonists represent an attractive strategy for the treatment of pulmonary arterial hypertension (PAH). Therefore, in this study, we have explored the pulmonary vascular effects of the novel KV7 channel agonist URO-K10. Consequently, the vasodilator and electrophysiological effects of URO-K10 were tested in rat and human pulmonary arteries (PA) and PA smooth muscle cells (PASMC) using myography and patch-clamp techniques. Protein expression was also determined by Western blot. Morpholino-induced knockdown of KCNE4 was assessed in isolated PA. PASMC proliferation was measured by BrdU incorporation assay. In summary, our data show that URO-K10 is a more effective relaxant of PA than the classical KV7 activators retigabine and flupirtine. URO-K10 enhanced KV currents in PASMC and its electrophysiological and relaxant effects were inhibited by the KV7 channel blocker XE991. The effects of URO-K10 were confirmed in human PA. URO-K10 also exhibited antiproliferative effects in human PASMC. Unlike retigabine and flupirtine, URO-K10-induced pulmonary vasodilation was not affected by morpholino-induced knockdown of the KCNE4 regulatory subunit. Noteworthy, the pulmonary vasodilator efficacy of this compound was considerably increased under conditions mimicking the ionic remodelling (as an in vitro model of PAH) and in PA from monocrotaline-induced pulmonary hypertensive rats. Taking all together, URO-K10 behaves as a KCNE4-independent KV7 channel activator with much increased pulmonary vascular effects compared to classical KV7 channel activators. Our study identifies a promising new drug in the context of PAH

The influence of initial xylose concentration, agitation, and aeration on ethanol production by Pichia stipitis from rice straw hemicellulosic hydrolysate

Rice straw hemicellulosic hydrolysate was used as fermentation medium for ethanol production by Pichia stipitis NRRL Y-7124. Shaking bath experiments were initially performed aiming to establish the best initial xylose concentration to be used in this bioconversion process. In the sequence, assays were carried out under different agitation (100 to 200 rpm) and aeration (V flask/V medium ratio varying from 2.5 to 5.0) conditions, and the influence of these variables on the fermentative parameters values (ethanol yield factor, Y P/S; cell yield factor, Y X/S; and ethanol volumetric productivity, Q P) was investigated through a 22 full-factorial design. Initial xylose concentration of about 50 g/l was the most suitable for the development of this process, since the yeast was able to convert substrate in product with high efficiency. The factorial design assays showed a strong influence of both process variables in all the evaluated responses. The agitation and aeration increase caused a deviation in the yeast metabolism from ethanol to biomass production. The best results (Y P/S = 0.37 g/g and Q P = 0.39 g/l.h) were found when the lowest aeration (2.5 V flask/V medium ratio) and highest agitation (200 rpm) levels were employed. Under this condition, a process efficiency of 72.5% was achieved. These results demonstrated that the establishment of adequate conditions of aeration is of great relevance to improve the ethanol production from xylose by Pichia stipitis, using rice straw hemicellulosic hydrolysate as fermentation medium.The financial support from Fapesp (Brazil) is gratefully acknowledged

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