Stat3 orchestrates interaction between endothelial and tumor cells and inhibition of Stat3 suppresses brain metastasis of breast cancer cells

Brain metastasis is a major cause of morbidity and mortality in patients with breast cancer. Our previous studies indicated that Stat3 plays an important role in brain metastasis. Here, we present evidence that Stat3 functions at the level of the microenvironment of brain metastases. Stat3 controlled constitutive and inducible VEGFR2 expression in tumor-associated brain endothelial cells. Furthermore, inhibition of Stat3 by WP1066 decreased the incidence of brain metastases and increased survival in a preclinical model of breast cancer brain metastasis. WP1066 inhibited Stat3 activation in tumor-associated endothelial cells, reducing their infiltration and angiogenesis. WP1066 also inhibited breast cancer cell invasion. Our results indicate that WP1066 can inhibit tumor angiogenesis and brain metastasis mediated by Stat3 in endothelial and tumor cells.     

Passive smoking does not increase hydrogen peroxide (H2O2) levels in exhaled breath condensate in 9-year-old healthy children

Environmental tobacco smoke, also called passive smoking, was shown to have adverse effects on the health of children. Hydrogen peroxide (H2O2) is proposed as a sensitive marker of oxidative injury and inflammatory processes in the airways, being increased in adult active cigarette smokers. We tested whether passive smoking had an influence on H2O2 exhalation in healthy children. Thirty healthy passive smoking and 24 nonexposed healthy children aged 9 years were included in the study. Exhaled breath condensate (EBC) was obtained by spontaneous tidal volume breathing with EcoScreen (Jaeger, Germany). All subjects underwent flow-volume measurements immediately after EBC collection. Levels of H2O2 were measured fluorimetrically with the homovanillic acid method. Lung function did not differ between the passive smoking and nonexposed children groups. In the passive smoking group, EBC H2O2 concentration (median and range) was 0.32 (0.00-1.20) microM, and did not differ significantly (P >0.05) from that found in the nonexposed group, i.e., 0,22 (0.00-0.68) microM. Exhaled H2O2 did not correlate with spirometric parameters (FEV1, FEV1%FVC, and MEF50%FVC) in either group. We conclude that passive smoking does not increase H2O2 exhalation in healthy children.     

Measurement of fractional flow reserve in patients with multi-vessel coronary artery disease and borderline lesions prevents unnecessary revascularisation procedures

BACKGROUND: Patients with multi-vessel coronary artery disease (CAD) are selected for percutaneous coronary interventions (PCI) or surgical revascularisation. The appropriateness of "ad hoc" PCI of borderline lesions (<70% of lumen diameter) in patients with a multi-vessel CAD has not been proven. However, delayed PCI of another lesion and gaining additional information from non-invasive tests is not a widely accepted strategy. When left anterior descending (LAD) coronary artery is one of the affected vessels, selection for surgical revascularisation is most likely. AIM: To assess long-term outcome in patients with multi-vessel CAD and borderline lesions, including LAD, in whom fractional flow reserve (FFR) in all affected vessels was measured and used for selection for PCI or conservative treatment. METHODS: The study group consisted of 16 patients with stable angina (11 males, mean age 60+/-9 years) with 34 lesions localised in the main epicardial coronary arteries [LAD / left main (LM) / right coronary artery (RCA) / intermediate branch (IB) / circumflex artery (Cx) - 15/1/5/5/8] of which at least two were borderline stenoses. Each lesion underwent FFR measurement. "Ad hoc" PCI was performed when FFR was <0.75, and conservative therapy was instituted when FFR was >0.75. RESULTS: Of 34 lesions, in 8 (23%) the FFR value was <0.75 and these lesions were treated with PCI (LAD/IB/Cx - 3/2/3). In the remaining 26 (77%) lesions, FFR was >0.75 and conservative therapy was instituted. During the mean follow-up of 15+/-6 months (range 6-28 months, median 15 months) in 8 of 9 conservatively treated patients no aggravation of anginal symptoms nor other coronary events were observed. One patient developed acute myocardial infarction due to thrombus occluding a borderline LAD lesion. Of 8 lesions treated with PCI (baseline FFR = 0.63+/-0.10 vs post-PCI FFR = 0.92+/-0.08, p=0.0002), in one case an in-stent restenosis in LAD occurred 9 months after PCI. Of a total of 26 lesions which were conservatively treated (mean FFR 0.91+/-0.05), in 2 (7.7%) the progression of CAD was noted. CONCLUSIONS: In patients with multi-vessel CAD and borderline lesions, FFR measurement identifies those, who can be treated conservatively with a good long-term outcome, and prevents unnecessary PCI.     

Validation of coronary flow reserve measurements by thermodilution in clinical practice.

BACKGROUND: Coronary flow reserve (CFR) and fractional flow reserve (FFR) provide complementary information on the coronary circulation. Using a pressure wire, it is possible to calculate CFR by thermodilution (CFR(thermo)), so that FFR and CFR can be measured with a single guide wire. The present multicentric study was performed to compare the feasibility of CFR(thermo)obtained with an improved algorithm and a standardized injection technique and its agreement with Doppler-derived CFR (CFR(Doppler)). METHODS AND RESULTS: In 86 patients with coronary artery disease recruited during 1 week in eight centres FFR, CFR(thermo)and CFR(Doppler)were measured. FFR could be obtained in all patients (100%). An optimal CFR(Doppler)could be obtained in 69% of the patients. CFR(thermo)could be obtained in 97% of the patients. A significant correlation was found between CFR(Doppler)and CFR(thermo)(r=0.79, P<0.0001) but CFR(thermo)tended to be higher than CFR(Doppler). CONCLUSIONS: In a setting close to 'real world' practice, this multicentric study confirms the feasibility and reliability of thermodilution-derived CFR. In addition, the safety and the swiftness of assessing FFR and CFR with one single guide wire makes the latter a unique clinical tool for the evaluation of the coronary circulation.     

Normal values for maximal static inspiratory and expiratory pressures in healthy children

Maximal static respiratory pressures are a simple measure of respiratory muscle strength. In order to construct a set of equations describing normal values, we measured maximal inspiratory (P(Imax)) and expiratory (P(Emax)) pressures in 296 children (144 boys and 152 girls), aged 7-14 years, in sitting and standing positions.The boys reached higher values in sitting and standing positions for P(Imax) (-8.29 +/- 2.69 and -8.19 +/- 2.73 kPa, respectively) and P(Emax) (8.02 +/- 2.32 and 7.94 +/- 2.32 kPa, respectively) than girls (-6.53 +/- 1.99 and -6.60 +/- 2.03 kPa for P(Imax) and 6.91 +/- 1.79 and 7.13 +/- 1.81 kPa for P(Emax) for sitting and standing positions, respectively); the differences between boys and girls were highly significant (P < 0.001 in all instances). There were no differences regarding body position during measurements in both genders. Multiple correlation analysis showed significant correlations of pressures to age in boys in all cases, but in girls only for P(Imax) in standing position. Therefore, equations describing reference values were constructed with respect to age as the independent variable. Maximal pressures also correlated with maximal inspiratory and expiratory flows.The measurements of P(Imax) and P(Emax) are useful in assessing respiratory muscle strength despite their relatively large variability. P(Imax) and P(Emax) also correlate with maximum peak expiratory and inspiratory flows. Children generate lower pressures and lower maximal flows than adolescents and adults.     

Genomic predictors of patterns of progression in glioblastoma and possible influences on radiation field design

Journal of Neuro-Oncology - We present a retrospective investigation of the role of genomics in the prediction of central versus marginal disease progression patterns for glioblastoma (GBM)....     

Rivaroxaban and Apixaban for Initial Treatment of Acute Venous Thromboembolism of Atypical Location

Objectives

To assess the outcome of direct oral anticoagulants (DOACs), specifically Xa inhibitors: rivaroxaban and apixaban, for the treatment of venous thromboembolism (VTE) of atypical location (VTE-AL), portal, mesenteric, hepatic, splenic, gonadal, renal, and cerebral veins, prospectively collected data of Mayo Thrombophilia Clinic Registry were used.

Towards selective electrochemical conversion of glycerol to 1,3-propanediol

1,3-propanediol (1,3-PD) is a bulk chemical with myriad applications in polymers, lubricants, cosmetics, foods industries and in the synthesis of heterocyclic compounds. Current commercial production of 1,3-PD involves a thermocatalytic process using acrolein (DuPont) and ethylene oxide (Shell) as starting feedstock. These feedstocks are petroleum-based and there are many efforts at using glycerol as low cost biomass-derived feedstock for 1,3-PD production. A number of catalyst designs and bacterial & fungal strains are being explored for respective catalytic and fermentation routes to glycerol-to-1,3-PD. However, the electrochemical method received little attention for the purpose. In this work, in order to explore the possibility of using partly refined glycerol byproduct of biodiesel production as feedstock, we investigated conversion and 1,3-PD selectivity of glycerol electrolysis in chloride media. We demonstrated selective glycerol-to-1,3-PD conversion using Pt or RuO₂-based dsa as anode and Zn or Pb as cathode in NaCl and KCl at pH 1. This electrochemical glycerol-to-1,3-PD conversion is not only green, it is a potential process network loop between biodiesel production and chlor-alkali industry.

Glycerol electrolysis in chloride media allows a green and sustainable route production to 1,3-propanediol and also benefits from easy integration into the chlor-alkali industry.     

Early bioprosthetic mitral valve thrombosis

We present a case of a 70 year-old woman operated due to severe mitral regurgitation. Early after surgery transthoracic echocardiography revealed the decreased effective orifice area of the implanted bioprosthetic valve and the stenotic features of transvalvular flow. Transesophageal echocardiography (TEE) disclosed a thrombotic cause of heterograft dysfunction. Due to the clinical deterioration and the unclear cause of prosthesis stenosis, the patient was reoperated. Intra-operatively bioprosthetic mitral valve thrombosis was confirmed. Precipitating factors of this rare complication including cardiac device related infective endocarditis (CDRIE) and the diagnostic applicability of TEE in this clinical scenario are discussed.