Nucleosomes indicate the in vitro radiosensitivity of irradiated bronchoepithelial and lung cancer cells

Nucleosomes, which are typical cell death products, are elevated in the serum of cancer patients and are known to rapidly increase during radiotherapy. As both normal and malignant cells are damaged by irradiation, we investigated to which extent both cell types contribute to the release of nucleosomes. We cultured monolayers of normal bronchoepithelial lung cells (BEAS-2B, n = 18) and epithelial lung cancer cells (EPLC, n = 18), exposed them to various radiation doses (0, 10 and 30 Gy) and observed them for 5 days. Culture medium was changed every 24 h. Subsequently, nucleosomes were determined in the supernatant by the Cell Death Detection-ELISA(plus) ( Roche Diagnostics). Additionally, the cell number was estimated after harvesting the cells in a second preparation. After 5 days, the cell number of BEAS-2B cultures in the irradiated groups (10 Gy: median 0.03 x 10(6) cells/culture, range 0.02-0.08 x 10(6) cells/culture; 30 Gy: median 0.08 x 10(6) cells/culture, range 0.02-0.14 x 10(6) cells/culture) decreased significantly (10 Gy: p = 0.005; 30 Gy p = 0.005; Wilcoxon test) compared to the non-irradiated control group (median 4.81 x 10(6) cells/culture, range 1.50-9.54 x 10(6) cells/culture). Consistently, nucleosomes remained low in the supernatant of nonirradiated BEAS-2B. However, at 10 Gy, BEAS-2B showed a considerably increasing release of nucleosomes, with a maximum at 72 h ( before irradiation: 0.24 x 10(3) arbitrary units, AU, range 0.13-4.09 x 10(3) AU, and after 72 h: 1.94 x 10(3) AU, range 0.11-5.70 x 10(3) AU). At 30 Gy, the release was even stronger, reaching the maximum earlier (at 48 h, 11.09 x 10(3) AU, range 6.89-18.28 x 10(3) AU). In non-irradiated EPLC, nucleosomes constantly increased slightly. At 10 Gy, we observed a considerably higher release of nucleosomes in EPLC, with a maximum at 72 h (before irradiation: 2.79 x 10(3) AU, range 2.42-3.80 x 10(3) AU, and after 72 h: 7.16 x 10(3) AU, range 4.30-16.20 x 10(3) AU), which was more than 3.5 times higher than in BEAS-2B. At 30 Gy, the maximum (6.22 x 10(3) AU, range 5.13-9.71 x 10(3) AU) was observed already after 24 h. These results indicate that normal bronchoepithelial and malignant lung cancer cells contribute to the release of nucleosomes during irradiation in a dose-and time-dependent manner with cancer cells having a stronger impact at low doses. Copyright (C) 2004 S. Karger AG, Basel

Kinetics of 5-aminolevulinic acid-induced fluorescence in organ cultures of bronchial epithelium and tumor

Background: 5-Aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PPIX) fluorescence improves the differentiation of tumor and normal tissue in the bladder, skin and brain. Objective: The kinetics of 5-ALA-induced protoporphyrin IX (PPIX) fluorescence in organ cultures of normal human bronchial epithelium and cocultures of bronchial epithelium and tumor have been studied. Methods: Cultured biopsies of bronchial epithelium were exposed for 5 or 15 min, or continuously to 5-ALA. PPIX fluorescence was quantified for up to 300 min by spectroscopy. Cocultures of normal bronchial epithelium and a non-small-cell lung cancer cell line (EPLC-32M1) were incubated with 5-ALA. Space-resolved fluorescence microscopy was used to quantify PPIX fluorescence kinetics in the tumor and normal epithelium. Results: In cultures of normal epithelium, PPIX fluorescence kinetics were shown to depend on the duration of exposure to 5-ALA. There was a trend to higher fluorescence intensities with longer exposure times. In cocultures of bronchial epithelium and tumor, increases of fluorescence intensity were significantly greater in the tumor. Best tumor/normal tissue fluorescence ratios were found between 110 and 160 min after exposure to 5-ALA. Conclusion: Data obtained in this coculture system of bronchial epithelium and tumor is valuable to optimize modalities of fluorescence bronchoscopy for the diagnosis of early bronchial carcinoma. Copyright (C) 2002 S. Karger AG, Basel

Vibrational contribution to the thermodynamics of nanosized precipitates: vacancy-copper clusters in bcc-Fe

Within the harmonic approximation, the effects of lattice vibration on the thermodynamics of nano-sized coherent clusters in bcc-Fe consisting of vacancies and/or copper are investigated. A combination of on-lattice simulated annealing based on Metropolis Monte Carlo simulations and off-lattice relaxation by Molecular Dynamics is applied to obtain the most stable cluster configurations at T = 0 K. The most recent interatomic potential built within the framework of the embedded atom method for the Fe-Cu system is used. The vibrational part of the total free energy of defect clusters in bcc-Fe is calculated using their phonon density of states. The total free energy of pure bcc-Fe and fcc-Cu as well as the total formation free energy and the total binding free energy of the vacancy-copper clusters are determined for finite temperatures. Our results are compared with the available data from previous investigations performed using empirical many-body interatomic potentials and first-principle methods. For further applications in rate theory and object kinetic Monte Carlo simulations, the vibrational effects evaluated in the present study are included in the previously derived analytical fits based on the classical capillary model.Comment: 6 figure

Patient-reported outcomes of pain and physical functioning in neurofibromatosis clinical trials.

ObjectiveTumors and other disease complications of neurofibromatosis (NF) can cause pain and negatively affect physical functioning. To document the clinical benefit of treatment in NF trials targeting these manifestations, patient-reported outcomes (PROs) assessing pain and physical functioning should be included as study endpoints. Currently, there is no consensus on the selection and use of such measures in the NF population. This article presents the recommendations of the PRO group of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration for assessing the domains of pain and physical functioning for NF clinical trials.MethodsThe REiNS PRO group reviewed and rated existing PRO measures assessing pain intensity, pain interference, and physical functioning using their systematic method. Final recommendations are based primarily on 4 main criteria: patient characteristics, item content, psychometric properties, and feasibility for clinical trials.ResultsThe REiNS PRO group chose the Numeric Rating Scale-11 (≥8 years) to assess pain intensity, the Pain Interference Index (6-24 years) and the Patient-Reported Outcome Measurement Information System (PROMIS) Pain Interference Scale (≥18 years) to evaluate pain interference, and the PROMIS Physical Functioning Scale to measure upper extremity function and mobility (≥5 years) for NF clinical trials.ConclusionsThe REiNS Collaboration currently recommends these PRO measures to assess the domains of pain and physical functioning for NF clinical trials; however, further research is needed to evaluate their use in individuals with NF. A final consensus recommendation for the pain interference measure will be disseminated in a future publication based on findings from additional published research

Nutrition support in cancer patients: a brief review and suggestion for standard indications criteria

The indications of nutrition support in cancer patients have been subject to controversy. Most studies address the effects of the method in increasing the survival or the tumor response rate. Few studies have focused on the effects in improving quality of life. After a brief review, we described the results of a study, which evaluated the effects of protein-caloric supplementation on the quality of life parameters in a group of head and neck cancer patients submitted to radiotherapy. The results support the suggestion of creating standard criteria to indicate nutrition support in cancer patients. Based on our findings, nutrition support should be indicated for cancer patients considering the potential effects to improve the quality of life

Clinical assessment of the physical activity pattern of chronic fatigue syndrome patients: a validation of three methods

Contains fulltext : 79568.pdf (publisher's version ) (Open Access)BACKGROUND: Effective treatment of chronic fatigue syndrome (CFS) with cognitive behavioural therapy (CBT) relies on a correct classification of so called 'fluctuating active' versus 'passive' patients. For successful treatment with CBT is it especially important to recognise the passive patients and give them a tailored treatment protocol. In the present study it was evaluated whether CFS patient's physical activity pattern can be assessed most accurately with the 'Activity Pattern Interview' (API), the International Physical Activity Questionnaire (IPAQ) or the CFS-Activity Questionnaire (CFS-AQ). METHODS: The three instruments were validated compared to actometers. Actometers are until now the best and most objective instrument to measure physical activity, but they are too expensive and time consuming for most clinical practice settings. In total 226 CFS patients enrolled for CBT therapy answered the API at intake and filled in the two questionnaires. Directly after intake they wore the actometer for two weeks. Based on receiver operating characteristic (ROC) curves the validity of the three methods were assessed and compared. RESULTS: Both the API and the two questionnaires had an acceptable validity (0.64 to 0.71). None of the three instruments was significantly better than the others. The proportion of false predictions was rather high for all three instrument. The IPAQ had the highest proportion of correct passive predictions (sensitivity 70.1%). CONCLUSION: The validity of all three instruments appeared to be fair, and all showed rather high proportions of false classifications. Hence in fact none of the tested instruments could really be called satisfactory. Because the IPAQ showed to be the best in correctly predicting 'passive' CFS patients, which is most essentially related to treatment results, it was concluded that the IPAQ is the preferable alternative for an actometer when treating CFS patients in clinical practice

Spectropolarimetry of the Massive Post-Red Supergiants IRC +10420 and HD 179821

We present medium resolution spectropolarimetry and long term photo-polarimetry of two massive post-red supergiants, IRC +10420 and HD 179821. The data provide new information on their circumstellar material as well as their evolution. In IRC +10420, the polarization of the Halpha line is different to that of the continuum, which indicates that the electron-scattering region is not spherically symmetric. The observed long term changes in the polarimetry can be associated with an axi-symmetric structure, along the short axis of the extended reflection nebulosity. Long term photometry reveals that the star increased in temperature until the mid-nineties, after which the photospheric flux in the optical levelled off. As the photometric changes are mostly probed in the red, they do not trace high stellar temperatures sensitively. And so, it is not obvious whether the star has halted its increase in temperature or not. For HD 179821 we find no polarization effects across any absorption or emission lines, but observe very large polarization changes of order 5% over 15 years. Unexpectedly, during the same period, the optical photometry displayed modest variability at the 0.2 magnitude level. Several explanations for this puzzling fact are discussed. Most of which, involving asymmetries in the circumstellar material, seem to fail as there is no evidence for the presence of hot, dusty material close to the star. Alternatively, the variations can be explained by the presence of a non-radially pulsating photosphere. Changes in the photometry hint at an increase in temperature corresponding to a change through two spectral subclasses over the past ten years.Comment: 13 pages, 6 figures, MNRAS accepte

Grain Surface Models and Data for Astrochemistry

AbstractThe cross-disciplinary field of astrochemistry exists to understand the formation, destruction, and survival of molecules in astrophysical environments. Molecules in space are synthesized via a large variety of gas-phase reactions, and reactions on dust-grain surfaces, where the surface acts as a catalyst. A broad consensus has been reached in the astrochemistry community on how to suitably treat gas-phase processes in models, and also on how to present the necessary reaction data in databases; however, no such consensus has yet been reached for grain-surface processes. A team of ∼25 experts covering observational, laboratory and theoretical (astro)chemistry met in summer of 2014 at the Lorentz Center in Leiden with the aim to provide solutions for this problem and to review the current state-of-the-art of grain surface models, both in terms of technical implementation into models as well as the most up-to-date information available from experiments and chemical computations. This review builds on the results of this workshop and gives an outlook for future directions

Screening for Domestic Violence Among Adult Women in the United States

BACKGROUND: Domestic violence is a problem frequently encountered in health care settings and a risk factor for physical and mental health problems. OBJECTIVE: To provide nationally representative estimates of rates of domestic violence screening among women, to identify predictors of screening, and to describe settings where women are screened. DESIGN AND PARTICIPANTS: We examined 4,821 women over the age of 18 from the second wave of Healthcare for Communities, a nationally representative household telephone survey conducted in 2000–2001. MEASUREMENTS: Self-reports concerning whether the respondent was ever asked about domestic or family violence by any health care provider. RESULTS: Only 7% (95% CI, 6%–8%) of women reported they were ever asked about domestic violence or family violence by a health care professional. Of women who were asked about abuse, nearly half (46%) were asked in a primary care setting, and 24% were asked in a specialty mental health setting. Women with risk factors for domestic violence were more likely to report being asked about it by a health care professional, but rates were still low. CONCLUSIONS: Self-reported rates of screening for domestic violence are low even among women at higher risk for abuse. These findings reinforce the importance of developing training and raising awareness of domestic violence and its health implications. This is especially true in primary care and mental health specialty settings