Sleeping with time in mind? A literature review and a proposal for a screening questionnaire on self-awakening.

Some people report being able to spontaneously "time" the end of their sleep. This ability to self-awaken challenges the idea of sleep as a passive cognitive state. Yet, current evidence on this phenomenon is limited, partly because of the varied definitions of self-awakening and experimental approaches used to study it. Here, we provide a review of the literature on self-awakening. Our aim is to i) contextualise the phenomenon, ii) propose an operating definition, and iii) summarise the scientific approaches used so far. The literature review identified 17 studies on self-awakening. Most of them adopted an objective sleep evaluation (76%), targeted nocturnal sleep (76%), and used a single criterion to define the success of awakening (82%); for most studies, this corresponded to awakening occurring in a time window of 30 minutes around the expected awakening time. Out of 715 total participants, 125 (17%) reported to be self-awakeners, with an average age of 23.24 years and a slight predominance of males compared to females. These results reveal self-awakening as a relatively rare phenomenon. To facilitate the study of self-awakening, and based on the results of the literature review, we propose a quick paper-and-pencil screening questionnaire for self-awakeners and provide an initial validation for it. Taken together, the combined results of the literature review and the proposed questionnaire help in characterising a theoretical framework for self-awakenings, while providing a useful tool and empirical suggestions for future experimental studies, which should ideally employ objective measurements.

A PPAR-gamma agonist attenuates pulmonary injury induced by irradiation in a murine model.

PURPOSE/OBJECTIVE(S): Due to its anti-inflammatory, antifibrotic and antineoplastic properties, the PPAR-γ agonist rosiglitazone is of interest in the prevention and therapy of radiation-induced pulmonary injury. We evaluated the radioprotective effects of rosiglitazone in a murine model of pulmonary damage to determine whether radioprotection was selective for normal and tumor tissues. METHODS: Lungs in C57BL/6J mice were irradiated (19 Gy) with or without rosiglitazone (RGZ, 5mg/kg/day for 16 weeks, oral gavage). Computed tomography (CT) was performed and Hounsfield Units (HU) were determined during the observation period. Histological analysis and evaluation of fibrosis/inflammatory markers by western blot were performed at 16 weeks. A549 tumor-bearing CD1 mice were irradiated (16 Gy) with or without RGZ, and tumor volumes were measured at 35 days. RESULTS: Rosiglitazone reduced radiologic and histologic signs of fibrosis, inflammatory infiltrate, alterations to alveolar structures, and HU lung density that was increased due to irradiation. RGZ treatment also significantly decreased Col1, NF-kB and TGF-ß expression and increased Bcl-2 protein expression compared to the irradiation group and reduced A549 clonogenic survival and xenograft tumor growth. CONCLUSIONS: Rosiglitazone exerted a protective effect on normal tissues in radiation-induced pulmonary injury, while irradiated lung cancer cells were not protected in vivo and in vitro. Thus, rosiglitazone could be proposed as a radioprotective agent in the treatment of lung cancer.

Organs at risk in the brain and their dose-constraints in adults and in children: a radiation oncologist's guide for delineation in everyday practice.

PURPOSE: Accurate organs at risk definition is essential for radiation treatment of brain tumors. The aim of this study is to provide a stepwise and simplified contouring guide to delineate the OARs in the brain as it would be done in the everyday practice of planning radiotherapy for brain cancer treatment. METHODS: Anatomical descriptions and neuroimaging atlases of the brain were studied. The dosimetric constraints used in literature were reviewed. RESULTS: A Computed Tomography and Magnetic Resonance Imaging based detailed atlas was developed jointly by radiation oncologists, a neuroradiologist and a neurosurgeon. For each organ brief anatomical notion, main radiological reference points and useful considerations are provided. Recommended dose-constraints both for adult and pediatric patients were also provided. CONCLUSIONS: This report provides guidelines for OARs delineation and their dose-constraints for the treatment planning of patients with brain tumors.

Adjuvant and salvage radiotherapy after prostatectomy: outcome analysis of 307 patients with prostate cancer.

AIM: In men with adverse pathology after radical prostatectomy, the most appropriate timing to administer radiotherapy (RT) remains a topic of debate. We analyzed in terms of efficacy, prognostic factors and toxicity the two therapeutic strategies: immediate postoperative radiotherapy (PORT) and salvage radiotherapy (SART). MATERIALS AND METHODS: Between January 1995 and November 2010, 307 patients underwent adjuvant or salvage radiotherapy, after prostatectomy. RESULTS: In the PORT group, 42 patients (20.7 %) had biochemical failure, with a median time to biochemical failure of 1.8 years; two parameters (age at diagnosis and PSA pre-RT) resulted to be significant at the survival analysis for overall survival (p = 0.003 and p = 0.046, respectively). In the SART group, 33 patients (31.7 %) had biochemical relapse; sixteen patients died of prostate cancer; postoperative hormones therapy, conformal radiotherapy and level of PSA pre-RT >1.0 ng/ml resulted to be significant at the survival analysis, p = 0.009, p = 0.039 and p = 0.002, respectively. CONCLUSION: Our study is limited by its retrospective and nonrandomized design. As such, decisions to treat with adjuvant or salvage radiotherapy and the time to initiate therapy were based on patient preference and physician counseling. Our recommendation is to suggest adjuvant radiotherapy for all patients with adverse prognostic factors and to reserve salvage radiotherapy for low-risk patients, when the biochemical recurrence occurs.

Predictive factors of [18F]-Choline PET/CT in 170 patients with increasing PSA after primary radical treatment.

AIM: The purpose of this study was to evaluate the potential usefulness of [18F]-Choline PET/CT in the restaging of prostate cancer patients, who presented a rising PSA. MATERIALS AND METHODS: We evaluated 170 prostate cancer patients, previously radically treated, that were referred for restaging with [18F]-Choline PET/CT. RESULTS: A total of 129 patients (median PSA 4.29 ng/ml at relapse) showed one or more areas of high uptake on PET/CT scan, while 41 patients with a median PSA of 1.07 ng/ml at relapse showed negative PET/CT scans. No false negative was found, while 31 patients were identified as false positive. Specificity of Choline PET/CT in our series was 56.9 %, while sensibility was 100 %. At the time of restaging, a PSA value superior or equal to 1 ng/ml was found to be a statistically significant predictive factor of PET positivity, either at the univariate (p < 0.0001) and at the multivariate analysis (p < 0.0001). CONCLUSIONS: Based on our findings, [18F]-Choline PET/CT is confirmed as a useful diagnostic tool to detect early recurrence, in patients with increasing PSA after primary treatment. However, in case of a mild increase in PSA, positive results must be validated with other techniques, as specificity and positive predictive value of [18F]-Choline PET/CT decrease with the lower values of PSA.

Association between single nucleotide polymorphisms in the XRCC1 and RAD51 genes and clinical radiosensitivity in head and neck cancer.

PURPOSE: Individual variability in radiosensitivity is large in cancer patients. Single nucleotide polymorphisms (SNPs) in genes involved in DNA repair and in protection against reactive oxygen species (ROS) could be responsible for such cases of radiosensitivity. We investigated the association between the occurrence of acute reactions in 101 patients with squamous cell carcinoma of the head and neck (SCCHN) after radiotherapy (RT) and five genetic polymorphisms: XRCC1 c.1196A>G, XRCC3 c.722C>T, RAD51 (c.-3429G>C, c.-3392G>T), and GSTP1 c.313A>G. MATERIALS AND METHODS: Genetic polymorphisms were detected by high resolution melting analysis (HRMA). The development of acute reactions (oral mucositis, skin erythema and dysphagia) associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for biologically effective dose (BED). RESULTS: Development of grade ≥2 mucositis was increased in all patients (chemo-radiotherapy and radiotherapy alone) with XRCC1-399Gln allele (HR=1.72). The likelihood of developing grade ≥2 dysphagia was higher in carriers of RAD51 c.-3429 CC/GC genotypes (HR=4.00). The presence of at least one SNP or the co-presence of both SNPs in XRCC1 p.Gln399Arg /RAD51 c.-3429 G>C status were associated to higher likelihood of occurrence of acute toxicities (HR=2.03). CONCLUSIONS: Our findings showed an association between genetic polymorphisms, XRCC1 c.1196A>G and RAD51 c.-3429 G>C, and the development of radiation-induced toxicities in SCCHN patients.