Predictive factors for beneficial application of high-frequency electromagnetics for tumour vaporization and coagulation in neurosurgery

<p>Abstract</p> <p>Objective</p> <p>To identify preoperative and intraoperative factors and conditions that predicts the beneficial application of a high-frequency electromagnetic field (EMF) system for tumor vaporization and coagulation.</p> <p>Methods</p> <p>One hundred three subsequent patients with brain tumors were microsurgically treated using the EMF system in addition to the standard neurosurgical instrumentarium. A multivariate analysis was performed regarding the usefulness (ineffective/useful/very helpful/essential) of the new technology for tumor vaporization and coagulation, with respect to tumor histology and location, tissue consistency and texture, patients' age and sex.</p> <p>Results</p> <p>The EMF system could be used effectively during tumor surgery in 83 cases with an essential contribution to the overall success in 14 cases. In the advanced category of effectiveness (very helpful/essential), there was a significant difference between hard and soft tissue consistency (50 of 66 cases vs. 3 of 37 cases). The coagulation function worked well (very helpful/essential) for surface (73 of 103 cases) and spot (46 of 103 cases) coagulation when vessels with a diameter of less than one millimeter were involved. The light-weight bayonet hand piece and long malleable electrodes made the system especially suited for the resection of deep-seated lesions (34 of 52 cases) compared to superficial tumors (19 of 50 cases).</p> <p>The EMF system was less effective than traditional electrosurgical devices in reducing soft glial tumors. Standard methods where also required for coagulation of larger vessels.</p> <p>Conclusion</p> <p>It is possible to identify factors and conditions that predict a beneficial application of high-frequency electromagnetics for tumor vaporization and coagulation. This allows focusing the use of this technology on selective indications.</p

Sequential and direct two-photon double ionization of D2 at FLASH

ABSTRACT: Sequential and direct two-photon double ionization (DI) of D2 molecule is studied experimentally and theoretically at a photon energy of 38.8 eV. Experimental and theoretical kinetic energy releases of D++D+ fragments, consisting of the contributions of sequential DI via the D2+(1ssg) state and direct DI via a virtual state, agree well with each other

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events

A descriptive analysis of relations between parents' self-reported smoking behavior and infants' daily exposure to environmental tobacco smoke

<p>Abstract</p> <p>Background</p> <p>The aims of the present study were to examine relations between parents' self-reported smoking behavior and infants' daily exposure to environmental tobacco smoke, as assessed by urinary cotinine-to-creatinine ratio (CCR), and to describe the CCR over seven days among infants at home.</p> <p>Methods</p> <p>A convenience sample of 27 households was drawn. Each household had to have at least one daily tobacco smoker and one child up to three years of age. Over a seven-day period, urine samples were obtained from the child daily. To examine relations between parents' self-reported smoking and infants' daily CCR, generalized estimating equation (GEE) analysis was used.</p> <p>Results</p> <p>The data revealed that infants from households with indoor smoking had higher CCRs than infants in households with outdoor smoking. CCRs were higher in girls than in boys. Older infants had lower CCRs than younger infants. Smoking outside the home versus inside the home, infant's gender, and infants' age accounted for 68% of the variance in CCR in a GEE data analysis model. No increase or decrease of CCR over time was found.</p> <p>Conclusion</p> <p>The findings suggest that parents' self-reported smoking indoors at home versus outdoors is predictive of CCR among infants three and younger. Higher CCR concentrations in girls' urine need further examination. Furthermore, significant fluctuations in daily CCR were not apparent in infants over a seven-day time period.</p

Radiobiological restrictions and tolerance doses of repeated single-fraction hdr-irradiation of intersecting small liver volumes for recurrent hepatic metastases

<p>Abstract</p> <p>Background</p> <p>To assess radiobiological restrictions and tolerance doses as well as other toxic effects derived from repeated applications of single-fraction high dose rate irradiation of small liver volumes in clinical practice.</p> <p>Methods</p> <p>Twenty patients with liver metastases were treated repeatedly (2 - 4 times) at identical or intersecting locations by CT-guided interstitial brachytherapy with varying time intervals. Magnetic resonance imaging using the hepatocyte selective contrast media Gd-BOPTA was performed before and after treatment to determine the volume of hepatocyte function loss (called pseudolesion), and the last acquired MRI data set was merged with the dose distributions of all administered brachytherapies. We calculated the BED (biologically equivalent dose for a single dose d = 2 Gy) for different α/β values (2, 3, 10, 20, 100) based on the linear-quadratic model and estimated the tolerance dose for liver parenchyma D₉₀as the BED exposing 90% of the pseudolesion in MRI.</p> <p>Results</p> <p>The tolerance doses D₉₀after repeated brachytherapy sessions were found between 22 - 24 Gy and proved only slightly dependent on α/β in the clinically relevant range of α/β = 2 - 10 Gy. Variance analysis showed a significant dependency of D₉₀with respect to the intervals between the first irradiation and the MRI control (p < 0.05), and to the number of interventions. In addition, we observed a significant inverse correlation (p = 0.037) between D₉₀and the pseudolesion's volume. No symptoms of liver dysfunction or other toxic effects such as abscess formation occurred during the follow-up time, neither acute nor on the long-term.</p> <p>Conclusions</p> <p>Inactivation of liver parenchyma occurs at a BED of approx. 22 - 24 Gy corresponding to a single dose of ~10 Gy (α/β ~ 5 Gy). This tolerance dose is consistent with the large potential to treat oligotopic and/or recurrent liver metastases by CT-guided HDR brachytherapy without radiation-induced liver disease (RILD). Repeated small volume irradiation may be applied safely within the limits of this study.</p

In vivo assessment of catheter positioning accuracy and prolonged irradiation time on liver tolerance dose after single-fraction 192Ir high-dose-rate brachytherapy

<p>Abstract</p> <p>Background</p> <p>To assess brachytherapy catheter positioning accuracy and to evaluate the effects of prolonged irradiation time on the tolerance dose of normal liver parenchyma following single-fraction irradiation with ¹⁹²Ir.</p> <p>Materials and methods</p> <p>Fifty patients with 76 malignant liver tumors treated by computed tomography (CT)-guided high-dose-rate brachytherapy (HDR-BT) were included in the study. The prescribed radiation dose was delivered by 1 - 11 catheters with exposure times in the range of 844 - 4432 seconds. Magnetic resonance imaging (MRI) datasets for assessing irradiation effects on normal liver tissue, edema, and hepatocyte dysfunction, obtained 6 and 12 weeks after HDR-BT, were merged with 3D dosimetry data. The isodose of the treatment plan covering the same volume as the irradiation effect was taken as a surrogate for the liver tissue tolerance dose. Catheter positioning accuracy was assessed by calculating the shift between the 3D center coordinates of the irradiation effect volume and the tolerance dose volume for 38 irradiation effects in 30 patients induced by catheters implanted in nearly parallel arrangement. Effects of prolonged irradiation were assessed in areas where the irradiation effect volume and tolerance dose volume did not overlap (mismatch areas) by using a catheter contribution index. This index was calculated for 48 irradiation effects induced by at least two catheters in 44 patients.</p> <p>Results</p> <p>Positioning accuracy of the brachytherapy catheters was 5-6 mm. The orthogonal and axial shifts between the center coordinates of the irradiation effect volume and the tolerance dose volume in relation to the direction vector of catheter implantation were highly correlated and in first approximation identically in the T1-w and T2-w MRI sequences (<it>p </it>= 0.003 and <it>p </it>< 0.001, respectively), as were the shifts between 6 and 12 weeks examinations (<it>p </it>= 0.001 and <it>p </it>= 0.004, respectively). There was a significant shift of the irradiation effect towards the catheter entry site compared with the planned dose distribution (<it>p </it>< 0.005). Prolonged treatment time increases the normal tissue tolerance dose. Here, the catheter contribution indices indicated a lower tolerance dose of the liver parenchyma in areas with prolonged irradiation (<it>p </it>< 0.005).</p> <p>Conclusions</p> <p>Positioning accuracy of brachytherapy catheters is sufficient for clinical practice. Reduced tolerance dose in areas exposed to prolonged irradiation is contradictory to results published in the current literature. Effects of prolonged dose administration on the liver tolerance dose for treatment times of up to 60 minutes per HDR-BT session are not pronounced compared to effects of positioning accuracy of the brachytherapy catheters and are therefore of minor importance in treatment planning.</p

Molecular Dynamics Analysis Reveals Structural Insights into Mechanism of Nicotine N-Demethylation Catalyzed by Tobacco Cytochrome P450 Mono-Oxygenase

CYP82E4, a cytochrome P450 monooxygenase, has nicotine N-demethylase (NND) activity, which mediates the bioconversion of nicotine into nornicotine in senescing tobacco leaves. Nornicotine is a precursor of the carcinogen, tobacco-specific nitrosamine. CYP82E3 is an ortholog of CYP82E4 with 95% sequence identity, but it lacks NND activity. A recent site-directed mutagenesis study revealed that a single amino acid substitution, i.e., cysteine to tryptophan at the 330 position in the middle of protein, restores the NND activity of CYP82E3 entirely. However, the same amino acid change caused the loss of the NND activity of CYP82E4. To determine the mechanism of the functional turnover of the two molecules, four 3D structures, i.e., the two molecules and their corresponding cys–trp mutants were modeled. The resulting structures exhibited that the mutation site is far from the active site, which suggests that no direct interaction occurs between the two sites. Simulation studies in different biological scenarios revealed that the mutation introduces a conformation drift with the largest change at the F-G loop. The dynamics trajectories analysis using principal component analysis and covariance analysis suggests that the single amino acid change causes the opening and closing of the transfer channels of the substrates, products, and water by altering the motion of the F-G and B-C loops. The motion of helix I is also correlated with the motion of both the F-G loop and the B-C loop and; the single amino acid mutation resulted in the curvature of helix I. These results suggest that the single amino acid mutation outside the active site region may have indirectly mediated the flexibility of the F-G and B-C loops through helix I, causing a functional turnover of the P450 monooxygenase

The two Titan stellar occultations of 14

[1] We report the observation of two stellar occultations by Titan on 14 November 2003, using stations in the Indian Ocean, southern Africa, Spain, and northern and southern Americas. These occultations probed altitudes between $550 and 250 km ($1 to 250 mbar) in Titan&apos;s upper stratosphere. The light curves reveal a sharp inversion layer near 515 ± 6 km altitude (1.5 mbar pressure level), where the temperature increases by 15 K in only 6 km. This layer is close to an inversion layer observed fourteen months later by the Huygens HASI instrument during the entry of the probe in Titan&apos;s atmosphere on 14 January 2005 À1 near the equator, and progressively weaker winds as more southern latitudes are probed. The haze distribution around Titan&apos;s limb at 250 km altitude is close to that predicted by the Global Circulation Model o

Causal effect of plasminogen activator inhibitor type 1 on coronary heart disease

Background--Plasminogen activator inhibitor type 1 (PAI-1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAI-1 levels are associated with increased risk of coronary heart disease (CHD). However, it is unclear whether the association reflects a causal influence of PAI-1 on CHD risk. Methods and Results--To evaluate the association between PAI-1 and CHD, we applied a 3-step strategy. First, we investigated the observational association between PAI-1 and CHD incidence using a systematic review based on a literature search for PAI-1 and CHD studies. Second, we explored the causal association between PAI-1 and CHD using a Mendelian randomization approach using summary statistics from large genome-wide association studies. Finally, we explored the causal effect of PAI-1 on cardiovascular risk factors including metabolic and subclinical atherosclerosis measures. In the systematic meta-analysis, the highest quantile of blood PAI-1 level was associated with higher CHD risk comparing with the lowest quantile (odds ratio=2.17; 95% CI: 1.53, 3.07) in an age- and sex-adjusted model. The effect size was reduced in studies using a multivariable-adjusted model (odds ratio=1.46; 95% CI: 1.13, 1.88). The Mendelian randomization analyses suggested a causal effect of increased PAI-1 level on CHD risk (odds ratio=1.22 per unit increase of log-transformed PAI-1; 95% CI: 1.01, 1.47). In addition, we also detected a causal effect of PAI-1 on elevating blood glucose and high-density lipoprotein cholesterol. Conclusions--Our study indicates a causal effect of elevated PAI-1 level on CHD risk, which may be mediated by glucose dysfunction