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We investigated the mechanisms involved in the resistance to cell death observed in epithelial cancers. Here, we identify that primary epithelial cancer cells from colon, breast and lung carcinomas express high levels of the antiapoptotic proteins PED, cFLIP, Bcl-xL and Bcl-2. These cancer cells produced interleukin-4 (IL-4), which amplified the expression levels of these antiapoptotic proteins and prevented cell death induced upon exposure to TRAIL or other drug agents. IL-4 blockade resulted in a significant decrease in the growth rate of epithelial cancer cells and sensitized them, both in vitro and in vivo, to apoptosis induction by TRAIL and chemotherapy via downregulation of the antiapoptotic factors PED, cFLIP, Bcl-xL and Bcl-2. Furthermore, we provide evidence that exogenous IL-4 was able to upregulate the expression levels of these antiapoptotic proteins and potently stabilized the growth of normal epithelial cells rendering them apoptosis resistant. In conclusion, IL-4 acts as an autocrine survival factor in epithelial cells. Our results indicate that inhibition of IL-4/IL-4R signaling may serve as a novel treatment for epithelial cancers.Cell Death and Differentiation (2008) 15, 762–772; doi:10.1038/sj.cdd.4402305; published online 18 January 2008 [ABSTRACT FROM AUTHOR]

Severe brain injuries have long-term consequences on functional status and psychosocial functioning. Family life can be greatly influenced as well, and features of high caregiver burden can emerge. Although the data on caregivers' distress are constantly increasing, less information is available about the role of family functioning. Thirty caregivers of hospitalised patients with severe brain injuries received questionnaires for the evaluation of caregiver burden, family functioning and perceived social support. A semi-structured interview was performed for the evaluation of quality of life. Family cohesion and adaptability positively correlated with caregivers' quality of life and perceived social support. Partner caregivers' scores were significantly higher on the time-dependent burden than those of sons and daughters, whereas the latter scored higher on the emotional burden.

Saliva represents a low stress, not-invasively collected matrix that allows steroid hormone monitoring in athletes by reflecting type, intensity and duration of exercise. Whole body cryotherapy (WBC) consists of short whole-body exposures to extremely cold air (-110° to -140°C) which, despite being initially used to treat inflammatory diseases, is currently acquiring increasing popularity in sports medicine. Cryostimulation practice is now widely accepted as an effective treatment to accelerate muscle recovery in rugby players. The aim of this work was to study the changes of steroid hormones in saliva of rugby players after both 2 and 14 consecutive WBC sessions, in order to investigate the effects of the treatment on their salivary steroid hormonal profile. Twenty-five professional rugby players, belonging to the Italian National Team, underwent a 7-day cryotherapy protocol consisting of 2 daily sessions. Saliva samples were taken in the morning prior to the start of the WBC, in the evening after the end of the second WBC, and in the morning of the day after the last WBC session. The samples were analyzed for cortisol, DHEA, testosterone and estradiol using competitive enzyme-linked immunosorbent assays. Cortisol and DHEA showed a reduction already after the 2 WBC sessions of the first day; after 14 consecutive WBC sessions cortisol, DHEA, and estradiol levels decreased, while testosterone increased as did the testosterone to cortisol ratio. These results were confirmed by the fact that the majority of subjects showed variations exceeding the critical difference (CD). In conclusion, we found that WBC acutely affects the salivary steroid hormone profile, and the results are evident already after only one twice-daily session. Most significantly, after one-week of consecutive twice-daily WBC sessions, all the hormones were modified. This is the first experimental report that links changes in the hormonal asset to WBC.

The aim of this study is to evaluate the correlation between different measures of quality of life (QoL), functional status and mood status in patients with amyotrophic lateral sclerosis (ALS). A sample of 40 patients with ALS was recruited and scales for the evaluation of health-related QoL (SF36), patient-centered QoL (SEIQoL), functional status (ALSFRS) and depression (ZDS) have been administered to them. All the correlations (Pearson's r) between the scores have been considered and the t-test was performed in order to compare male with female patients. No correlation emerged between the different measures of QoL and functional status, apart from the scores of the Physical Functioning subscale of the SF36 which resulted positively correlated (p < 0.01) with those of the ALSFRS. Mood status resulted negatively correlated with many aspects of health-related QoL but not with patient-centred QoL. Data suggest that the relationship between functional status and different domains of QoL in this population of patients with a severely compromising disease is not linear and that the satisfaction with life of the patients themselves is not strongly related to the level of physical impairment.

The sharing of information and the growth of knowledge together represent a foundation for the promotion of quality improvement of health care systems. This paper concerns knowledge, not only from an epistemological point of view, but also from a pragmatic one. In our paper, knowledge is discussed as the hub to promote better decision making and continuous professional development. Effective thinking is particularly needed. The critical point is to think about how health care systems can develop both an effective knowledge management network and how health-care organizations can actually be based on it. In this way, knowledge and knowledge hierarchy are defined according to Russel Achkoff's vision. Generally, knowledge is crucial in decision-making, and Evidence-Based Medicine has its roots in knowledge. In particular, information management is the basis for a significant production of knowledge to promote good health-care decision-making. Thus, relationships between knowledge management and Evidence-Based Medicine are discussed, and a new paradigm is proposed: the Evidence-Based Knowledge Management. Finally, the role of Evidence-Based Knowledge Management within Clinical Governance is discussed together with some considerations about clinical governance implementation problems in Italy.

We have attempted to identify those subgroups of patients most likely to develop lymph node metastases from squamous cell carcinoma of the lower lip (LLSSC). A total of 97 subjects, who did not undergo elective neck dissection, were recruited into the 60-month disease-free survival study. After univariate analysis, tumour size, histological grading, maximal thickness, perineural invasion and immunoreactivity to cyclin D1 and p27Kip1 proteins proved to be significant factors. Tests of the effect of interaction between p27Kip1 LI and tumour thickness yielded that the impact of tumour thickness on the risk of lymph node metastases was modified by the percentage of p27Kip1 positive cells. Subsequent to models of multivariate analysis, tumour size, positive cyclin D1 protein expression, maximal thickness (> 5 mm), p27Kip1 LI (%) and the interaction term between p27Kip1 LI and tumour thickness retained strong independent predictive values for lymph node metastases. We suggest that immunohistochemistry for cyclin D1 and p27Kip1 may prove to be valuable ancillary tests for identifying LLSSC with metastatic potential.

We studied a consecutive series of 95 patients undergoing radical surgical resection of lower lip squamous cell carcinoma (LLSCC) to assess the correlation between lymph node status and several prognostic variables, such as sex and age, tumour size, histologic grading, maximal microscopic tumour thickness, perineural infiltration and p27Kip1 protein status, to see which of these might be predictive of the development of lymph node metastases. Statistical analysis demonstrated a significant association between node status and tumour size, histological grading, maximal thickness, perineural invasion and p27Kip1 protein expression; additionally to node metastasis, low p27Kip1 protein expression was significant correlated with high microscopic thickness. These results indicate that lower lip squamous cell carcinomas of >2 cm, with G3-G4 histological grading, maximal thickness of >6 mm, perineural invasion and low p27Kip1 protein expression (LI<19.7%) are at high risk for the development of lymph node metastases.

The authors evaluated 36 patients (72 eyes) who had either Stage 4 or Stage 5 retinopathy of prematurity (ROP) with standardized A-scan and B-scan echography. The eyes were evaluated for vitreous opacities, retrolental membranes, and retinal detachments. Stage 5 retinal detachments were present in 94% (68 of 72) of the eyes with 65% (47 of 72) having a wide anterior and narrow posterior configuration. Anterior retinal loops were noted in 36% of the eyes. Subretinal opacities were present in 47% of the eyes. Choroidal thickening and intraocular calcium were noted in 22% and 14% of eyes, respectively. The axial eye length was measured and adjusted for the differences in chronological and gestational age and compared with data from normal eyes. This showed that eyes with ROP were much smaller. The standardized A-scan was helpful in confirming the diagnosis of retinal detachment, evaluating the peripheral retina, and examining the subretinal space. The combination of A-scan and B-scan echography is helpful in predicting anatomic findings in patients with ROP undergoing surgery.