Compliance to radiation therapy of head and neck cancer patients and impact on treatment outcome

Aims: The aims of the study were to evaluate head and neck cancer (HNC) patient’s compliance to the planned radiation therapy (RT) using the department policy established in 2005 at IPOCFG and to estimate the impact on treatment outcome due to failure in receiving RT as prescribed. Materials and methods: 359 HNC patients irradiated from 2007 to 2013 were included in this study. Patient cohort was divided into Group 1: patients receiving RT as prescribed and Group 2: patients that interrupted or suspended RT. Group Tox is the subgroup of patients that interrupted RT due to toxicity or intercurrent disease. Number and causes for treatment interruptions were assessed. The cumulative incidence of locoregional control (LRC), disease-free survival (DFS) and overall survival for Groups 1 and 2 was determined. Cox regression was performed to investigate potential hazard factors and logistic regression was made to determine risk factors related to treatment interruptions. Results: Major causes for treatment interruptions were toxicity plus intercurrent disease (41.7 %) and public holidays (30.1 %). 10.3 % of the patients interrupted 3-9 days. Significant differences in survival distributions of the LRC between Groups 1 and 2, of up to 19 %, were found in the subgroup of patients with N2-3 tumours, for post-operative RT and for concomitant RT. Treatment breaks larger than two days had an almost fourfold increased risk of poorer LRC and DFS. Conclusions: Twin accelerators and treating on public holidays are effective measures minimizing RT breaks. For HNC, patient compliance is mostly limited by RT sideeffects. Efforts to maintain RT biological effective dose in HNC must be always undertaken (AU)

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Chromatin Proteomics Reveals Variable Histone Modifications during the Life Cycle of Trypanosoma cruzi

Histones are well-conserved proteins that form the basic structure of chromatin in eukaryotes and undergo several post-translational modifications, which are important for the control of transcription, replication, DNA damage repair, and chromosome condensation. In early branched organisms, histones are less conserved and appear to contain alternative sites for modifications, which could reveal evolutionary unique functions of histone modifications in gene expression and other chromatin-based processes. Here, by using high-resolution mass spectrometry, we identified and quantified histone post-translational modifications in two life cycle stages of Trypanosoma cruzi, the protozoan parasite that causes Chagas disease. We detected 44 new modifications, namely: 18 acetylations, seven monomethylations, seven dimethylations, seven trimethylations, and four phosphorylations. We found that replicative (epimastigote stage) contains more histone modifications than nonreplicative and infective parasites (trypomastigote stage). Acetylations of lysines at the C-terminus of histone H2A and methylations of lysine 23 of histone H3 were found to be enriched in trypomastigotes. In contrast, phosphorylation in serine 23 of H2B and methylations of lysine 76 of histone H3 predominates in proliferative states. The presence of one or two methylations in the lysine 76 was found in cells undergoing mitosis and cytokinesis, typical of proliferating parasites. Our findings provide new insights into the role of histone modifications related to the control of gene expression and cell-cycle regulation in an early divergent organism

Ion-pair formation observed in a pulsed-field ionization photoelectron spectroscopic study of HF

The pulsed-field ionization (PFI) photoelectron (PE) spectrum of HF has been recorded at the chemical dynamics beamline of the advanced light source over the photon energy range 15.9-16.5 eV using a time-of-flight selection scheme at a resolution of 0.6 meV. Rotationally-resolved structure in the HF+(X 2 pi 3/2, 1/2, v+ = 0, 1) band systems are assigned. The spectral appearance of these systems agrees with a previous VUV laser PFI-PE study. Importantly, extensive rotationally-resolved structure between these two vibrational band systems is also observed. This is attributed to ion-pair formation via Rydberg states converging on the v+ = 1 vibrational levels of the HF+(X 2 pi 3/2, 1/2) spin-orbit states. These Rydberg states are assigned to the 1 sigma+ part of the nd-complexes (sigma, pi, and delta). Ion-pair formation is observed in this study by the detection of F- ions. Some partially rotationally-resolved structure in a previously published threshold photoelectron spectrum is similarly attributed to ion-pair formation (F- detection) through a combination of the v+ = 17 level of the (A 2 sigma+) 3s sigma Rydberg state and the (X 2 pi 3/2, 1/2, v+ = 1) 7d Rydberg states. On the basis of the present study, an accurate experimental value for the dissociation energy of the ground state of HF has been obtained, D0(HF) = 5.8650(5) eV.