Serum levels of mitochondrial inhibitory factor 1 are independently associated with long-term prognosis in coronary artery disease: the GENES Study

Background Epidemiological and observational studies have established that high-density lipoprotein cholesterol (HDL-C) is an independent negative cardiovascular risk factor. However, simple measurement of HDL-C levels is no longer sufficient for cardiovascular risk assessment. Therefore, there is a critical need for novel non-invasive biomarkers that would display prognostic superiority over HDL-C. Cell surface ecto-F1-ATPase contributes to several athero-protective properties of HDL, including reverse cholesterol transport and vascular endothelial protection. Serum inhibitory factor 1 (IF1), an endogenous inhibitor of ecto-F1-ATPase, is an independent determinant of HDL-C associated with low risk of coronary artery disease (CAD). This work aimed to examine the predictive value of serum IF1 for long-term mortality in CAD patients. Its informative value was compared to that of HDL-C. Method Serum IF1 levels were measured in 577 male participants with stable CAD (age 45–74 years) from the GENES (Genetique et ENvironnement en Europe du Sud) study. Vital status was yearly assessed, with a median follow-up of 11 years and a 29.5 % mortality rate. Cardiovascular mortality accounted for the majority (62.4 %) of deaths. Results IF1 levels were positively correlated with HDL-C (rs = 0.40; P < 0.001) and negatively with triglycerides (rs = −0.21, P < 0.001) and CAD severity documented by the Gensini score (rs = −0.13; P < 0.01). Total and cardiovascular mortality were lower at the highest quartiles of IF1 (HR = 0.55; 95 % CI, 0.38–0.89 and 0.50 (0.28–0.89), respectively) but not according to HDL-C. Inverse associations of IF1 with mortality remained significant, after multivariate adjustments for classical cardiovascular risk factors (age, smoking, physical activity, waist circumference, HDL-C, dyslipidemia, hypertension, and diabetes) and for powerful biological and clinical variables of prognosis, including heart rate, ankle-brachial index and biomarkers of cardiac diseases. The 10-year mortality was 28.5 % in patients with low IF1 (<0.42 mg/L) and 21.4 % in those with high IF1 (≥0.42 mg/L, P < 0.02). Conclusions We investigated for the first time the relation between IF1 levels and long-term prognosis in CAD patients, and found an independent negative association. IF1 measurement might be used as a novel HDL-related biomarker to better stratify risk in populations at high risk or in the setting of pharmacotherapy

AIC-144 cyclotron: present status

The presented AIC-144 cyclotron was designed and constructed 20 years ago in the Institute of Nuclear Physics in Kraków (Poland). Later on it was modernized, after the decision of creating the Hadron Radiotherapy Centre in Kraków was taken by the government. At present, the cyclotron is capable to deliver beams of protons (with energy up to 60 MeV), deuterons (with energy up to 30 MeV) and a-particles (with energy up to 60 MeV). The magnetic structure and the RF system were modernized (a new HF generator with output power 120 kW and frequency range 10-27 MHz was installed; an RF cavity resonator was reconstructed to improve the Q-factor at the highest frequencies). The new PIG source and system of central diaphragms was built to improve beams quality on the first turns. The single lamella and multilamella probes were fully reconstructed. Special effort was put on a highly efficient extraction system. The precession method for particles extraction was chosen as the best one. All computer simulations and experimental runs were done in close cooperation with specialists from the Laboratory of Nuclear Problems JINR, Dubna. The extraction system consists of 2 electrostatic deflectors, 3 magnetic channels (passive) and 4 coils for shaping of the 1st harmonic. So far, the beam extraction experiments were carried out for the proton beams with the final energy of 35 MeV, 48 MeV and 60 MeV. For all these energies the efficiency of extraction was above 50%. A computer remote control of the main magnet power supply and of the 24 correction coils was installed and put into operation. In the last 3 years, the internal beams of protons and a-particles were used to produce radioisotopes like 11C, 57Co, 83-85Sr, 102Rh, 111In, 173-175Hf, 178-181W

Simulation of operation modes of isochronous cyclotron by a new interative method

Operation mode simulation methods are based on selection of trim coil currents in the isochronous cyclotron for formation of the required magnetic field at a certain level of the main coil current. The traditional current selection method is based on finding a solution for all trim coils simultaneously. After setting the calculated operation mode, it is usually necessary to perform a control measurement of the magnetic field map and to repeat the calculation for a more accurate solution. The new current selection method is based on successively finding solutions for each particular trim coil. The trim coils are taken one by one in reverse order from the edge to the center of the isochronous cyclotron. The new operation mode simulation method is based on the new current selection method. The new method, as against the traditional one, includes iterative calculation of the kinetic energy at the extraction radius. A series of experiments on proton beam formation within the range of working acceleration radii at extraction energies from 32 to 59 MeV, which were carried out at the AIC144 multipurpose isochronous cyclotron (designed mainly for the eye melanoma treatment and production of radioisotopes) at the INP PAS (Kraków), showed that the new method makes unnecessary any control measurements of magnetic fields for getting the desired operation mode, which indicates a high accuracy of the calculation