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Background: Generic medicines are essential to controlling health expenditures. Their market share is still small in France. The discourse and practices of prescribers may play a major role in their use. The purpose of this study was to explore the knowledge, attitudes and practices of general practitioners (GPs) toward generic medicines in two French regions with the lowest penetration rate of these products., Methods: An observational study was carried out from October 2015 to February 2016 in Guadeloupe and Martinique. The first qualitative phase involved a diversified sample of 14 GPs who underwent semi-structured interviews. The second phase involved a random sample of 316 GPs (response rate = 74%) who were administered a structured questionnaire developed from the results of the first phase., Results: Seventy-eight percent of the participants defined a generic drug as a drug containing an active substance identical to a brand-name drug, but only 11% considered generic drugs to be equivalent to brand-name drugs, and the same proportion believed that the generic drugs were of doubtful quality. The primary recognized advantage of generic medicines was their lower cost (82%). The main drawbacks cited were the variability of their presentation (44%), the confusion that they caused for some patients (47%), frequent allegations of adverse side effects (37%) and a lack of efficacy (24%), and frequent refusal by patients (26%). Seventy-four percent of the participants stated that they adapted their prescribing practices to the situation, and of this group, 47% prescribed the originator product simply on demand., Conclusion: Most surveyed GPs were not hostile towards generic medicines. They were caught between the requirements of health insurance regimes and the opposition of numerous users and suggested that the patient information provided by health authorities should be improved and that drug composition and packaging should be made uniform.

Health is dependent on the living conditions and the socioeconomic environment of populations. The healthcare system tends to underestimate these aspects and thereby maintain, and even aggravate, the resulting social inequalities in health. It is essential that this situation is improved by adopting a global and interdisciplinary vision of healthcare and its social determinants., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Prenatal psychoactive substance exposure has significant impact on neonatal health and child development and the development of reliable biomarkers is critical. Meconium presents several advantages for detecting prenatal exposure to psychoactive substances, as it is easy to collect and provides a broad time frame of exposure (third trimester). The aim of our study was to compare the prevalence of alcohol, tobacco and/or cannabis use during the third trimester of pregnancy (using maternal self-reports) with the results of meconium testing of their metabolites in newborns (cotinine, ethyl-glucuronide (EtG) and cannabinoid metabolites). Among all deliveries (993) that occurred in all maternities in Rouen (Normandy) during a defined time period (5 consecutive weeks in August, 2010 and August, 2011), 724 mothers were included and 645 meconium samples were collected. Maternal self-reports, using the Addiction Severity Index (5th edition), and meconium samples were collected within 72 h of delivery. Cotinine detection appears highly correlated to maternal self-reports (Kappa value: 0.79; [95%CI: 0.73-0.85]). Moreover, detection in meconium seems more accurate in the prediction of neonatal consequences of prenatal tobacco exposure as compared to maternal self-reports. In contrast, we have found a lower concordance between maternal self-reports and meconium testing for EtG and cannabinoid metabolites (Kappa value: 0.13; [95%CI: 0.04-0.22] and: 0.30; [95%CI: -0.03-0.63], respectively); however the total number of EtG- and cannabinoid-positive meconium samples was small. Interestingly, meconium samples with the highest levels of EtG mainly corresponded to negative maternal self-reports. Fetal exposure to alcohol, tobacco or cannabis may also considerably differ as displayed in our pairs of dizygotic twins. Finally, a polyconsumption of these psychoactive substances was not frequently observed according to meconium testing. In conclusion, cotinine detection appears as a valuable meconium biomarker. EtG measurement in meconium samples seems interesting if there is any risk of high fetal exposure, whereas assessment of prenatal cannabis exposure, using meconium testing, needs to be improved., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Epidemiological studies have convincingly demonstrated that diets rich in fruits and vegetables play an important role in preventing cancer due to their polyphenol content. Among polyphenols, the anthocyanidins are known to possess anti-inflammatory, cardioprotective, anti-angiogenic, and anti-carcinogenic properties. Despite the well-known role of transforming growth factor-β (TGF-β) in high grade gliomas, the impact of anthocyanidins on TGF-β-induced epithelial-mesenchymal transition (EMT), a process that allows benign tumor cells to infiltrate surrounding tissues, remains poorly understood. The objective of this study is to investigate the impact of anthocyanidins such as cyanidin (Cy), delphinidin (Dp), malvidin (Mv), pelargonidin (Pg), and petunidin (Pt) on TGF-β-induced EMT and to determine the mechanism(s) underlying such action. Human U-87 glioblastoma (U-87 MG) cells were treated with anthocyanidins prior to, along with or following the addition of TGF-β. We found that anthocyanidins differently affected TGF-β-induced EMT, depending on the treatment conditions. Dp was the most potent EMT inhibitor through its inhibitory effect on the TGF-β Smad and non-Smad signaling pathways. These effects altered expression of the EMT mesenchymal markers fibronectin and Snail, as well as markedly reducing U-87 MG cell migration. Our study highlights a new action of anthocyanidins against EMT that supports their beneficial health and chemopreventive effects in dietary-based strategies against cancer. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Objectives: Assessing the quality of the clinical management of prostate cancer in the Midi-Pyrenean region in 2011., Methods: The study population was randomly selected among new cases of prostate cancer presented in Multidisciplinary Team Meeting (MTM) in 2011. The indicators defined with the professionals have evaluated the quality of the diagnostic care, when treatment started and at the time of the MTM., Results: Six hundred and thirty-three new patients were included (median age at diagnosis=69years, min: 48; max: 93). In diagnostic period, 92% of patients had a prostate biopsy. Performing a pelvic MRI, an abdomino-pelvic CT and bone scintigraphy concerned respectively 53%, 55% and 61% of intermediate or high-risk patients. The Gleason score, surgical margins and pathological stage were included in over 98% patient records treated by radical prostatectomy. A PSA assay in 3months after prostatectomy was found in 59% of surgical patients. The MTM was performed before treatment to 83% of patients. About three-quarters of surgical patients with stage pT≥3 or pN1 or with no healthy margins were discussed in MTM after surgery., Conclusion: Most of the studied indicators reach a high level. However, the lower level of realization of complementary examinations may question about their real place, accessibility and traceability., Level of Evidence: 4., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

In the field of health, evidence-based medicine and associated methods like randomised controlled trials (RCTs) have become widely used. RCT has become the gold standard for evaluating causal links between interventions and health results. Originating in pharmacology, this method has been progressively expanded to medical devices, non-pharmacological individual interventions, as well as collective public health interventions. Its use in these domains has led to the formulation of several limits, and it has been called into question as an undisputed gold standard. Some of those limits (e.g. confounding biases and external validity) are common to these four different domains, while others are more specific. This paper describes the different limits, as well as several research avenues. Some are methodological reflections aiming at adapting RCT to the complexity of the tested interventions, and at overcoming some of its limits. Others are alternative methods. The objective is not to remove RCT from the range of evaluation methodologies, but to resituate it within this range. The aim is to encourage choosing between different methods according to the features and the level of the intervention to evaluate, thereby calling for methodological pluralism., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Mother-son incest as well as female pedophilic disorder remain underrecognized and misdiagnosed. This is the case of a female child abuser who suffered from hypersexual disorder and mental retardation and whose son was viewed as a substitute transitional sexual partner. Our clinical case shared some common features with female sex offenders previously described in the literature but the association of sexual gratification and hypersexuality without pedophilic fantasies is quite uncommon in female child abusers.

This study has two objectives. First, to analyse the respective roles of parental BMI and the wider environment on children's BMI across childhood, using a counterfactual analysis. Second, to determine if the correlations between parents and offspring BMI are partly environmental. We used data on 4437 girls and 4337 boys born in 2000-2001 in the UK and included in the Millennium Cohort Study. Children's BMI was measured at ages 3years, 5years, 7years, and 11years. We described the environment using social class and behaviours within the family. At the age of 3, there was no link between the environment and children's BMI. In contrast, there was a clear link between the environment and BMI slopes between 3 and 11years of age. At the age of 11, we calculated that if all children had the most favourable environment, mean BMI would be reduced by 0.91kg/m(2) (95% CI: 0.57-1.26) for boys and by 1.65kg/m(2) (95% CI: 1.28-2.02) for girls. Associations between parents' and offspring BMI remained unchanged after adjustment for environmental variables. Conversely, the link between the environment and children's BMI is partly reduced after adjustment for parental BMI. This confirms that parental BMI is partly a broad proxy of the environment. We highlighted that if every child's environment was at its most favourable, the mean BMI would be significantly reduced. Thus, the recent rise is likely to be reversible., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

The cover of a recent issue of Science et Santé, the INSERM magazine, asked the following question concerning epigenetics: “What is the exact role played by the genome?”. Strangely, the first page of this same issue raised another question: “How to fight health inequalities?”. We will try to answer these two questions and determine the links between them by examining public health challenges and the questions raised by recent progress in biology, especially epigenetics. The results of this analysis support those of epidemiological studies highlighting the importance of examining the construction of health during life. These studies may throw new light on the issue of social inequalities in health and how to reduce these inequalities.

The generation of cyclopent-2-enylzinc from cyclopentadiene based on a titanium-catalyzed hydroalumination/transmetallation sequence is described. Applied to the allylmetallation of phenylglycinol-derived imines, this sequence leads to homoallylic amines with moderate to good stereoselectivities. The synthesis of disubstituted azetidines and piperidines illustrates the potential of the method.

The established causal relationship between the chronic inflammatory microenvironment, tumor development and cancer recurrence has provided leads for developing novel preventive strategies. Accumulating experimental, clinical and epidemiological data has provided support for the chemopreventive properties of olive oil compounds traditionally found within the Mediterranean diet. In this study, we investigated whether tyrosol (Tyr), hydroxytyrosol, oleuropein and oleic acid (OA), four compounds contained in extra virgin olive oil, can prevent tumor necrosis factor (TNF)-α-induced expression of cyclooxygenase (COX)-2 (an inflammation biomarker) in a human glioblastoma cell (U-87 MG) model. We found that Tyr and OA significantly inhibited TNF-α-induced COX-2 gene and protein expression, as well as PGE2 secretion. Both compounds also inhibited TNF-α-induced JNK and ERK phosphorylation, whereas only Tyr inhibited TNF-α-induced NF-κB phosphorylation. Paracrine-regulated migration of human brain microvascular endothelial cells (HBMECs) was assessed using growth factor-enriched conditioned media (CM) isolated from U-87 MG cells. We found that while PGE2 triggered HBMEC migration, the CM isolated from U-87 MG cells, where either COX-2 or NF-κB had been silenced or had been treated with Tyr or OA, exhibited decreased chemotactic properties. These observations demonstrate that olive oil compounds inhibit the effect of the chronic inflammatory microenvironment on glioblastoma progression through TNF-α actions and may be useful in cancer chemoprevention., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Cancer survivorship has emerged as an important aspect of oncology due to the possibility of physical and psychosocial complications. The purpose of this study was to assess the feasibility of the Ambulatory Medical Assistance for After Cancer (AMA-AC) procedure for monitoring lymphoma survivorship during the first year after chemotherapy., Methods: AMA-AC is based on systematic general practitioner (GP) consultations and telephone interventions conducted by a nurse coordinator (NC) affiliated to the oncology unit, while an oncologist acts only on demand. Patients are regularly monitored for physical, psychological and social events, as well as their health-related quality of life (HRQoL). Inclusion criteria were patients newly diagnosed with non-Hodgkin or Hodgkin lymphomas, who had been treated with anthracycline-based chemotherapy and were in complete remission after treatment., Results: All 115 patients and 113 collaborating GPs agreed to participate in the study. For patients who achieved one year of disease-free survival (n = 104) their assessments (438 in total) were fully completed. Eleven were excluded from analysis (9 relapses and 2 deaths). The most frequent complications when taking into account all grades were arthralgia (64.3%) and infections (41.7%). About one third of patients developed new diseases with cardiovascular complications as the most common. Psychological disorders such as anxiety, depression and post-traumatic stress disorder were diagnosed in 42.6% of patients. The data collected showed that Hodgkin lymphoma patients, females, and patients with lower HRQoL (mental component) at study entry were at greater risk for developing at least one psychological disorder., Conclusion: This study showed that AMA-AC is a feasible and efficient procedure for monitoring lymphoma survivorship in terms of GP and patient participation rates and adherence, and provides a high quality of operable data. Hence, the AMA-AC procedure may be transferable into clinical daily practice as an alternative to standard oncologist-based follow-up.

Introduction: Emphysematous pyelonephritis (EPN) is associated with high mortality rate, up to 25%. There is still conflicting reports regarding the most appropriate management, conservative versus nephrectomy., Objective: To describe the outcome of patients with EPN., Methods: We retrospectively reviewed the medical records of patients diagnosed with EPN by computed tomography from three tertiary institutes in Jeddah, Saudi Arabia. Type of management was classified as conservative and surgical. The conservative includes medical and minimally invasive procedures, such as percutaneous drainage and nephrostomy. The surgical which is nephrectomy. The outcome observed was preservation of the kidney function or patient's life., Results: A total of 10 patients were included (9 females and 1 male), median age was 55 years and 63% were diabetic. The most common presentation was flank pain (100%), fever (75%), and vomiting (63%). The most common organism isolated was Escherichia coli. Nephrectomy was not associated with increased survival rate, while conservative management was associated with a good outcome, less morbidity (not dialysis-dependent)., Conclusion: Nephrectomy was not associated with high survival rate. Patients managed conservatively had a better overall performance and better survival. This study will add to other studies, which are encouraging conservative management.

Background: Adherence to therapy has been established for years as a critical parameter for clinical benefit in medical oncology. This study aimed to assess, in the current practice, the influence of the socio-demographical characteristics and the place of treatment on treatment adherence and overall survival among diffuse large B-cell lymphoma patients., Methods: We analysed data from 380 patients enrolled in a French multi-centre regional cohort, with diffuse large B-cell lymphoma receiving first-line treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or R-CHOP-like regimens. Direct examination of administrative and medical records yielded the date of death. We studied the influence of patients' socio-demographic characteristics and place of treatment on the treatment adherence and overall survival, adjusted for baseline clinical characteristics. Treatment adherence was measured by the ratio between received and planned dose Intensity (DI), called relative DI (RDI) categorized in "lesser than 85%" and "at least 85%"., Results: During the follow-up, among the final sample 70 patients had RDI lesser than 85% and 94 deceased. Multivariate models showed that advanced age, poor international prognosis index (IPI) and treatment with R-CHOP 14 favoured RDI lesser than 85%. The treatment in a public academic centre favoured RDI greater than or equal to 85%. Poor adherence to treatment was strongly associated with poor overall survival whereas being treated in private centres was linked to better overall survival, after adjusting for confounders. No socioeconomic gradient was found on both adherence to treatment and overall survival., Conclusions: These results reinforce adherence to treatment as a critical parameter for clinical benefit among diffuse large B-cell lymphoma patients under R-CHOP. The place of treatment, but not the socioeconomic status of these patients, impacted both RDI and overall survival.

When estimating the causal effect of an exposure of interest on change in an outcome from baseline, the choice between a linear regression of change adjusted or unadjusted for the baseline outcome level is regularly debated. This choice mainly depends on the design of the study and the regression-to-the-mean phenomena. Moreover, it might be necessary to consider additional variables in the models (such as factors influencing both the baseline value of the outcome and change from baseline). The possible combinations of these elements make the choice of an appropriate statistical analysis difficult. We used directed acyclic graphs (DAGs) to represent these elements and to guide the choice of an appropriate linear model for the analysis of change. Combined with DAGs, we applied path analysis principles to show that, under some functional assumptions, estimations from the appropriate model could be unbiased. In the situation of randomized studies, DAG interpretation and path analysis indicate that unbiased results could be expected with both models. In the case of confounding, additional (and sometimes untestable) assumptions, such as the presence of unmeasured confounders, or effect modification over time should be considered. When the observed baseline value influences the exposure ("cutoff designs"), linear regressions adjusted for baseline level should be preferred to unadjusted linear regression analyses. If the exposure starts before the beginning of the study, linear regression unadjusted for baseline level may be more appropriate than adjusted analyses.

Success in developing therapeutic approaches to target brain tumor-associated inflammation in patients has been limited. Given that the inflammatory microenvironment is a hallmark signature of solid tumor development, anti-inflammatory targeting strategies have been envisioned as preventing glioblastoma initiation or progression. Consumption of foods from plant origin is associated with reduced risk of developing cancers, a chemopreventive effect that is, in part, attributed to their high content of phytochemicals with potent anti-inflammatory properties. We explored whether luteolin, a common flavonoid in many types of plants, may inhibit interleukin (IL)-1β function induction of the inflammation biomarker cyclooxygenase (COX)-2. We found that IL-1β triggered COX-2 expression in U-87 glioblastoma cells and synergized with luteolin to potentiate or inhibit that induction in a biphasic manner. Luteolin pretreatment of cells inhibited IL-1β-mediated phosphorylation of inhibitor of κB, nuclear transcription factor-κB (NF-κB) p65, extracellular signal-regulated kinase-1/2, and c-Jun amino-terminal kinase in a concentration-dependent manner. Luteolin also inhibited AKT phosphorylation and survivin expression, while it triggered both caspase-3 cleavage and expression of glucose-regulated protein 78. These effects were all potentiated by IL-1β, in part through increased nuclear translocation of NF-κB p65. Finally, luteolin was able to reduce IL-1 receptor gene expression, and treatment with IL-1 receptor antagonist or gene silencing of IL-1 receptor prevented IL-1β/luteolin-induced COX-2 expression. Our results document a novel adaptive cellular response to luteolin, which triggers anti-survival and anti-inflammatory mechanisms that contribute to the chemopreventive properties of this diet-derived molecule., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The population hospitalised in psychiatry seems more exposed to traumatic events than the French general population, with particularly more sexual aggressions. The aim of this study is to describe the population hospitalised in psychiatry and more precisely the traumatic history of these patients, their comorbidities (mental diseases and addictions), and socio economical level. This descriptive, cross sectional and retrospective study took place in the Crisis Center in the University Hospital in Martinique (French West Indies), from February to July 2013. A socio-demographic information, the Mini International Neuropsychiatric Interview 5.0, the Trauma History Questionnaire and the Impact Events Scale-Revised were realised with 49 of the 143 patients admitted during this period (34.3%). In this population, we found a mean of 6.5 (standart-deviation=4.2) different types of traumatic event, with 38.8% patients reporting a natural disaster, and 38.8% declaring at least one sexual aggression. In the 25 patients suffering from post-traumatic stress disorder, 66.7% underwent a sexual aggression, significatively during childhood (before 10 years old, P=0.01), and during adolescence (between 10 to 18 years old, P=0.01). These results underline the importance of a systematic screening of the traumatic profile: the characteristics of the traumatic events and its clinical impact.

Objective: This study aimed to test longitudinal associations linking the work-unit-level psychosocial and organizational work environment and biomechanical constraints to workers' shoulder pain in the French multi-centre cohort ORSOSA study of registered nurses (RN) and nursing assistants (NA)., Methods: We analyzed 1896 female RN and NA, who were free of shoulder pain in 2006 and in the same position and work unit in 2008. Incident shoulder pain (SP) was defined as self-reported pain that persists for ≥ 4 days and/or increases during a lateral movement of the arm away from the midline of the body (abduction). Both cross-sectional and longitudinal models were built to test if work-unit-level features or their influences on both work tasks and individual perception of the work environment directly influence the risk of developing incident SP., Results: RN in work units with understaffing issues or poor relationships reported higher levels of biomechanical constraints in movements and postures and a lower level of perceived job security and stability. NA who experienced such issues reported higher levels of biomechanical constraints in indirect patient-handling activities only. The exposure to these latter factors was associated with higher two-year incident SP among workers., Conclusion: This study shows that the work-unit-level organizational characteristics may impact workers' musculoskeletal disorders by conditioning both work-task-related biomechanical exposures and individual perception of the working environment. In healthcare settings, primary prevention programs to reduce MSD would benefit from a focus on work unit level exposures.

Background: Many studies have supported the role of organizational work factors (OWFs) on the risk of cardiovascular diseases (CVDs) and CVD risk factors, including arterial hypertension. However, a little information is available concerning the role of collective stressors deriving from work organization on nurse's risk of hypertension. This study aimed to test the independent longitudinal relationships linking the 2-year incidence of arterial hypertension to collective stressors at the work unit level, among baseline normotensive female hospital registered nurses and nursing assistants, after adjusting for known individual predictors of CVDs and for occupational stress., Method: Arterial hypertension was defined as the intake of antihypertensive drug or as blood pressure (BP) measures higher than 140  mmHg (SBP) or 90  mmHg (DBP) at both the clinical visit and 1 month later. We analyzed the effect of OWFs at the work unit level, constraints related to the physical work environment and the individual perception of the work environment in 2006 on the risk of arterial hypertension in 2008 among 1882 initially normotensive female healthcare workers followed in the French Organisation des soins et santé des soignants (ORSOSA) cohort., Results: We showed that OWFs at the work unit level may influence the 2-year risk of arterial hypertension independently of work factors at the worker level, baseline BP, age and BMI. In this study, OWFs affected 2-year risk of arterial hypertension only through direct effects., Conclusion: Our results pointed out the possibility of a primary prevention of arterial hypertension through interventions based at the work unit level among healthcare workers.

Vascular endothelial growth factor (VEGF) triggers crucial signaling processes that regulate tumor angiogenesis and, therefore, represents an attractive target for the development of novel anticancer therapeutics. Several epidemiological studies have confirmed that abundant consumption of foods from plant origin is associated with reduced risk of developing cancers. In the Mediterranean basin, the consumption of extra virgin olive oil is an important constituent of the diet. Compared to other vegetable oils, the presence of several phenolic antioxidants in olive oil is believed to prevent the occurrence of a variety of pathological processes, such as cancer. While the strong antioxidant potential of these molecules is well characterized, their antiangiogenic activities remain unknown. The aim of this study is to investigate whether tyrosol (Tyr), hydroxytyrosol (HT), taxifolin (Tax), oleuropein (OL) and oleic acid (OA), five compounds contained in extra virgin olive oil, can affect in vitro angiogenesis. We found that HT, Tax and OA were the most potent angiogenesis inhibitors through their inhibitory effect on specific autophosphorylation sites of VEGFR-2 (Tyr951, Tyr1059, Tyr1175 and Tyr1214) leading to the inhibition of endothelial cell (EC) signaling. Inhibition of VEGFR-2 by these olive oil compounds significantly reduced VEGF-induced EC proliferation and migration as well as their morphogenic differentiation into capillary-like tubular structures in Matrigel. Our study demonstrates that HT, Tax and OA are novel and potent inhibitors of the VEGFR-2 signaling pathway. These findings emphasize the chemopreventive properties of olive oil and highlight the importance of nutrition in cancer prevention., (© 2013 The Authors. Published by Elsevier Inc. All rights reserved.)

Licit and illicit substance use during pregnancy is a major public health concern. Alcohol and substance (tobacco, cannabis, cocaine...) use prevalence during pregnancy remains under estimated. Some studies have reported the prevalence of alcohol or substance use in different countries worldwide but most of them were based on the mother's interview. Consumption of one or more psychoactive substances during pregnancy may have serious consequences on the pregnancy and on the child development. However, the type of consequences is still a matter of controversies. The reasons are diverse: different rating scales, potential interactions with environmental and genetic factors. Considering the negative consequences of drug use during pregnancy, preventive campaigns against the use of drugs during pregnancy are strongly recommended.

Objective: To estimate the magnitude of over-diagnosis and of potential and actual over-treatment regarding prostate cancer, taking comorbidities into account., Materials and Methods: We used a sample collected by the French cancer registries of 1840 cases (T1: 583; T2: 1257) diagnosed in 2001. The proportion of over-diagnosed and over-treated patients was estimated by comparing life expectancy (LE), including or not comorbidities, with natural LE with cancer, using several assumptions from the literature. We distinguished potential and actual over-treatment according to the treatment that patients actually received., Results: Among patients with T1 tumors the proportion of potential over-treatment using LE adjusted for comorbidity varied from 29.5% to 53.5%, using LE adjusted on comorbidities, and varied from 9.3% to 22.2% regarding actual over-treatment. Between 7.7% and 24.4% of patient's receiving a radical prostatectomy, and between 30.8% and 62.5% of those receiving radiotherapy, were over-treated. Among patients with T2 tumors, the proportions of potential and actual over-treatment were 0.9% and 2.0%. Two per cent of patients receiving a radical prostatectomy and 4.9% of those receiving radiotherapy were over-treated. Comorbidities dramatically increased these proportions to nearly 100% of patients, with more than two comorbidities being potentially over-treated and around 33% actually over-treated., Conclusions: According to the French incidence, 3200-4800 French patients may be over-treated, among whom a large proportion of patients had comorbidities. The real issue is to offer the most appropriate treatment to people with low-grade tumors and comorbidities., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: This longitudinal study aimed to test the hypothesis that organizational work factors (OWFs) may be related to depressive symptoms through an increased effort-reward imbalance (ERI) ratio among registered nurses (RNs) and nursing assistants working in hospitals., Methods: We studied 2117 female RNs and nursing assistants who stayed in the same work unit and position during the follow-up from the ORSOSA (ORganisation des SOins-SAnté) longitudinal study. The work characteristics and workers' health were assessed in 2006 and 2008., Results: We confirmed our hypothesis of both direct and mediated effects of OWFs on workers' health. We showed that issues about patient-related information exchanges increased RNs' depressive disorders by increasing first a perceived ERI., Conclusions: Our results advocate integrating both the work organizational level and the individual level into preventive actions to improve workers' mental health.

The health of hospital workers, nurses and nurse-aids constitutes a public health challenge for three reasons: maintenance of personnel at work in a context in which many express their desire to quit their jobs, protection of their health, and maintenance of quality of care. ORSOSA (ORganisation des SOins et SAnté des soignants) is a multidisciplinary interventional population health research programme designed to improve quality of life in the workplace of healthcare workers. This programme is designed to develop a tool to diagnose psychosocial and organisational work factors (POWFs) and mechanical constraints (MC), and then to implement this method in primary prevention interventions. ORSOSA consists of two steps: research (ORSOSA 1) and intervention (ORSOSA 2). In ORSOSA 1, a prospective cohort of healthcare workers was developed to construct and validate the diagnostic tool of work-related constraints at the work unit level. ORSOSA 2 consists of using the tool to implement both a collective and consensual dynamic based on collective restitution of the strengths and weaknesses of the work unit in order to propose recommendations for better quality of life at work. ORSOSA is now deployed in 4 teaching hospitals (Lille, Bordeaux, Grenoble and Strasbourg), each with 5 peripheral hospitals. Evaluation and follow-up of the programme is ongoing.

Background: CSF-2 and CSF-3 confer proangiogenic and immunomodulatory properties to mesenchymal stromal cells (MSCs)., Results: Transcriptional regulation of CSF-2 and CSF-3 in concanavalin A-activated MSCs requires MT1-MMP signaling and is inhibited by EGCG., Conclusion: The chemopreventive properties of diet-derived EGCG alter MT1-MMP-mediated intracellular signaling., Significance: Pharmacological targeting of MSCs proangiogenic functions may prevent their contribution to tumor development. Epigallocatechin gallate (EGCG), a major form of tea catechins, possesses immunomodulatory and antiangiogenic effects, both of which contribute to its chemopreventive properties. In this study, we evaluated the impact of EGCG treatment on the expression of colony-stimulating factors (CSF) secreted from human bone marrow-derived mesenchymal stromal cells (MSCs), all of which also contribute to the immunomodulatory and angiogenic properties of these cells. MSCs were activated with concanavalin A (ConA), a Toll-like receptor (TLR)-2 and TLR-6 agonist as well as a membrane type 1 matrix metalloproteinase (MT1-MMP) inducer, which increased granulocyte macrophage-CSF (GM-CSF, CSF-2), granulocyte CSF (G-CSF, CSF-3), and MT1-MMP gene expression. EGCG antagonized the ConA-induced CSF-2 and CSF-3 gene expression, and this process required an MT1-MMP-mediated sequential activation of the Src and JAK/STAT pathways. Gene silencing of MT1-MMP expression further demonstrated its requirement in the phosphorylation of Src and STAT3, whereas overexpression of a nonphosphorylatable MT1-MMP mutant (Y573F) abrogated CSF-2 and CSF-3 transcriptional increases. Given that MSCs are recruited within vascularizing tumors and are believed to contribute to tumor angiogenesis, possibly through secretion of CSF-2 and CSF-3, our study suggests that diet-derived polyphenols such as EGCG may exert chemopreventive action through pharmacological targeting of the MT1-MMP intracellular signaling.

Renal transplantation is the choice treatment of end-stage renal disease. When it is not indicated or not immediately feasible, hemodialysis must be performed, preferably via a native arteriovenous fistula in the forearm. A pre-anastomotic occlusion of this type of fistula is often accompanied by a thrombosis of its draining vein. In some instances, the venous segment may remain permeable thanks to the development of arterial collateral pathways and may even allow efficient dialysis without any clinical syndrome of distal steal. We present the echo-Doppler, magnetic and angiographic characteristics of three of these collateralized shunts that have remained functional, in one of the cases following a percutaneous dilation.

Prostate cancer incidence has tripled in Luxembourg as in many other western countries. From 1982 to 2006, new cases increased from 80 to 309 per year, while the incidence (world stand.pop.) rose from 29.5 to 85 per 100 000 men. Since 1991 prostate cancer is the most frequent male cancer in Luxembourg, exceeding colo-rectal, lung and stomach cancer. Prostate cancer deaths have diminished from 64 in 1982 to 45 in 2006. This represents less than 10% of male cancer related deaths; it represents the third most frequent cancer death, behind lung and colo-rectal cancers. Annual mortality rate has decreased from 29 to 10 per 100 000 men during the same period, this difference between incidence and mortality is explained on the one hand by the widespread use of PSA since the 1990's and on the other hand by a better local control as well as a multidisciplinary approach of advanced disease. The increase of the incidence is particularly important in the 60 to 70 age group, while for men older than 70, the peak incidence was reached in 2002. A lowering of the age at diagnosis is confirmed by the 5-year age group analysis. The hospital cohort consists of 628 patients from the urological department of the Centre Hospitalier de Luxembourg diagnosed with prostate cancer between 1st January 1982 and 31st December 2006; follow-up ended 31st December 2011. During this period, age at diagnosis decreased from 71.5 to 68.9 years whereas the proportion of localized clinical stages increased from 44 to 70%. Median PSA dropped from 14.5 to 9 ng/ml. Furthermore the analysis of cancer specific mortality confirms the negative effects of an advanced clinical stage (10-year survival: 90% for localized disease, 60% for advanced disease) or a high PSA level at diagnosis (10-year survival: 97% if PSA < 4 ng/nl, 94% if 4 < PSA < 10, and 72% if PSA > 10 ng/ml), as well as a poor differentiation (60% 10-year survival compared to 90% for differentiated tumors). Kaplan-Meier curves show that long term surveillance is necessary as even tumors with a good initial prognosis may relapse after 10-12 years.

Several epidemiological studies have indicated that abundant consumption of foods from plant origin is associated with a reduced risk of developing several types of cancers. This chemopreventive effect is related to the high content of these foods in phytochemicals, such as polyphenols, that interfere with several processes involved in cancer progression including tumor cell growth, survival and angiogenesis. In addition to the low intake of plant-based foods, increased body mass and physical inactivity have recently emerged as other important lifestyle factors influencing cancer risk, leading to the generation of low-grade chronic inflammatory conditions which are a key process involved in tumor progression. The objectives of the current study are to investigate the inhibitory effects of these polyphenols on angiogenesis triggered by an inflammatory cytokine (IL-6) and to determine the mechanisms underlying this action. We found that, among the tested polyphenols, apigenin and luteolin were the most potent angiogenesis inhibitors through their inhibitory effect on the inflammatory cytokine IL-6/STAT3 pathway. These effects resulted in modulation of the activation of extracellular signal-regulated kinase-1/2 signaling triggered by IL-6, as well as in a marked reduction in the proliferation, migration and morphogenic differentiation of endothelial cells. Interestingly, these polyphenols also modulated the expression of IL-6 signal transducing receptor (IL-6Rα) and the secretion of the extracellular matrix degrading enzyme MMP-2 as well as the expression of suppressor of cytokine signaling (SOCS3) protein. Overall, these results may provide important new information on the role of diet in cancer prevention., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Despite being time-consuming and observer-dependent, CDUS is a method of choice for performing and controlling dialysis shunts. It contributes to increasing the number of native AVFs and enables early detection of lesions therefore allowing quick percutaneous or surgical therapy.

Propranolol, a non-selective β-adrenergic blocking drug, was recently reported to control the growth of hemangiomas, the most common vascular tumor of infancy. However, the mechanisms involved in this effect remain unknown. Here, we demonstrate that propranolol dose-dependently inhibited growth factor-induced proliferation of cultured human umbilical vein endothelial cells (HUVECs) through a G₀/G₁ phase cell cycle arrest. This was correlated to decreased cyclin D1, cyclin D3, and cyclin-dependent kinase CDK6 protein levels, while increases in the CDK inhibitors p15(INK4B), p21(WAF1/Cip1) and p27(Kip1) were observed. Chemotactic motility and differentiation of HUVECs into capillary-like tubular structures in Matrigel were also inhibited by propranolol. Furthermore, inhibition by propranolol of vascular endothelial growth factor (VEGF)-induced tyrosine phosphorylation of VEGF receptor-2 lead to inhibition of downstream signaling such as the activation of the extracellular signal-regulated kinase-1/2 and the secretion of the extracellular matrix degrading enzyme MMP-2. Taken together, these results demonstrate that propranolol interferes with several essential steps of neovascularization and opens up novel therapeutic opportunities for the use of β-blockers in the treatment of angiogenesis-dependent human diseases., (Copyright © 2010 Elsevier Inc. All rights reserved.)

All around the world, the potential consequences of the increasing use of psychoactive substances during pregnancy are a major public health concern. It is estimated that 20 to 30% of pregnant women use tobacco, 15% use alcohol, 3 to 10% use cannabis and 0.5 to 3% use cocaine. The estimation of tobacco consumption during pregnancy is better known as compared with alcohol and substance use prevalence during pregnancy, which remains under estimated or unknown. For example, in France, the prevalence of cannabis and cocaine use during pregnancy is unknown. In general, the prevalence of drug or alcohol use during pregnancy is estimated by extrapolating data from epidemiological studies conducted in the general population (in France or in other countries). However, drug or alcohol use in the general population may dramatically vary from one country to another. Even if some studies have reported the prevalence of alcohol or substance use in different countries around the world, most of them were based on the mother's interview. In most cases, the mother did not report exactly the amount of drugs or alcohol used. Further studies measuring alcohol or substance use in the mother's blood, hair or in the newborn's meconium are needed. In addition, different methodologies have been used in the literature (different types of interview, with or without biological measurements; different subjects included (in- or out-pregnant women, psychiatric comorbidities or not, different economic status, etc). Despite these methodological biases, the prevalence of drug or alcohol use increases in pregnant women, and in most cases, several drugs are associated. Most of the studies have used structured or semi-structured interviews such as the addiction severity index (ASI) or the alcohol use disorders identification test (AUDIT) to assess alcohol or drug consumption. In addition, the identification of risk factors for substance or alcohol use during pregnancy would allow the early detection of these high-risk pregnancies. Environmental factors such as low economic status or marital status may play an important role. Personality disorders may also contribute to substance or alcohol use during pregnancy. In fact, in most studies the quality of the obstetrical survey is lower in pregnant women using drugs or alcohol but it remains difficult to describe a specific at-risk profile in these pregnant women. Consumption of alcohol or of one or more psychoactive substances during pregnancy may have serious consequences on the pregnancy and on the child's development. Fetal alcoholism syndrome is the main etiology of mental retardation in France. We need to improve our knowledge of alcohol and substance use during pregnancy in order to target information for prevention campaigns and to implement specific mother and child medical care in high-risk populations., (Copyright (c) 2009 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

CD133 (prominin-1) is a transmembrane glycoprotein expressed at the surface of normal and cancer stem cells, progenitor cells, rod photoreceptor cells, and a variety of epithelial cells. Although CD133 is widely used as a marker of various somatic and putative cancer stem cells, its contribution to fundamental properties of stem cells such as self-renewal and differentiation remains unknown. CD133 contains a short C-terminal cytoplasmic domain with five tyrosine residues, including a consensus tyrosine phosphorylation site that has not yet been investigated. In this study, we show that CD133 is phosphorylated in human medulloblastoma D283 and Daoy cells, in a Src family kinase-dependent manner. The cytoplasmic domain of CD133 is tyrosine phosphorylated in Daoy cells overexpressing Src and Fyn tyrosine kinases, as well as in vitro using recombinant proteins. Deletion of the C-terminal cytoplasmic domain of CD133 considerably reduced its phosphorylation by Src. To identify the tyrosine phosphorylation sites in CD133, we used matrix-assisted laser desorption/ionization quadrupole time-of-flight (MALDI Q-TOF) and liquid chromatography tandem mass spectrometry (LC-MS/MS). Analysis of tyrosine-phosphorylated CD133 by mass spectrometry and site-directed mutagenesis identified tyrosine-828 and the nonconsensus tyrosine-852 as the major tyrosine phosphorylation sites both in vitro and in intact cells. Identification of CD133 as a substrate for Src-family tyrosine kinases suggests that the cytoplasmic domain of CD133 might play an important role in the regulation of its functions.

Medulloblastoma, the most common malignant brain tumor in children, is a highly metastatic disease, with up to 30% of children having evidence of disseminated disease at presentation. Recently, the hepatocyte growth factor (HGF) and its receptor, the tyrosine kinase Met, have emerged as key components of human medulloblastoma growth and metastasis, suggesting that inhibition of this pathway may represent an attractive target for the prevention and treatment of this disease. Using immunoblotting procedures, we observed that the dietary-derived flavonols quercetin, kaempferol, and myricetin inhibited HGF/Met signaling in a medulloblastoma cell line (DAOY), preventing the formation of actin-rich membrane ruffles and resulting in the inhibition of Met-induced cell migration in Boyden chambers. Furthermore, quercetin and kaempferol also strongly diminished HGF-mediated Akt activation. Interestingly, the inhibitory effects of quercetin on the tyrosine kinase receptor Met [half-maximal inhibitory effect (IC(50)) of 12 micromol/L] or on the Met-induced activation of Akt (IC(50) of 2.5 micromol/L) occurred at concentrations achievable through dietary approaches. These results highlight quercetin, kaempferol, and myricetin as dietary-derived inhibitors of Met activity and suggest that this inhibitory effect may contribute to the chemopreventive properties of these molecules.

Platelet-derived growth factor (PDGF)-dependent recruitment of mural cells such as pericytes and smooth muscle cells plays a central role in the maturation and stabilization of newly formed vasculature during angiogenesis. In this work, we show that the dietary flavones apigenin and luteolin may interfere with this event through their inhibitory effect on PDGF-dependent phosphorylation of PDGF receptor beta (PDGFR-beta) in smooth muscle cells. Inhibition of PDGFR-beta activity by apigenin and luteolin occurred at low concentrations of the molecules and resulted in the inhibition of extracellular signal-regulated kinase and Akt phosphorylation triggered by PDGF, as well as in a marked reduction of the migratory and invasive properties of these cells. Apigenin and luteolin also strongly inhibit the PDGF-dependent increase in vascular endothelial growth factor (VEGF) mRNA levels and the secretion of VEGF by smooth muscle cells as well as vessel formation in the mouse Matrigel plug assay, suggesting that the inhibitory effects of both molecules on smooth muscle cell function result in impaired angiogenesis. Overall, these results identify apigenin and luteolin as dietary-derived inhibitors of PDGFR-beta activity and suggest that this inhibitory effect may contribute to the chemopreventive properties of these molecules.

Most cancers are dependent on the growth of tumor blood vessels and inhibition of tumor angiogenesis may thus provide an efficient strategy to retard or block tumor growth. Recently, tumor vascular targeting has expanded to include not only endothelial cells (ECs) but also smooth muscle cells (SMCs), which contribute to a mature and functional vasculature. We have reported previously that delphinidin, a major biologically active constituent of berries, inhibits the vascular endothelial growth factor-induced phosphorylation of vascular endothelial growth factor receptor-2 and blocks angiogenesis in vitro and in vivo. In the present study, we show that delphinidin also inhibits activation of the platelet-derived growth factor (PDGF)-BB receptor-beta [platelet-derived growth factor receptor-beta (PDGFR-beta)] in SMC and that this inhibition may contribute to its antitumor effect. The inhibitory effect of delphinidin on PDGFR-beta was very rapid and led to the inhibition of PDGF-BB-induced activation of extracellular signal-regulated kinase (ERK)-1/2 signaling and of the chemotactic motility of SMC, as well as the differentiation and stabilization of EC and SMC into capillary-like tubular structures in a three-dimensional coculture system. Using an anthocyan-rich extract of berries, we show that berry extracts were able to suppress the synergistic induction of vessel formation by basic fibroblast growth factor-2 and PDGF-BB in the mouse Matrigel plug assay. Oral administration of the berry extract also significantly retarded tumor growth in a lung carcinoma xenograft model. Taken together, these results provide new insight into the molecular mechanisms underlying the antiangiogenic activity of delphinidin that will be helpful for the development of dietary-based chemopreventive strategies.

Background: Increasing incidence rates of testicular cancer have been reported worldwide over the last three decades. Trends over time in the incidence rates of germ cell tumours (GCTs) in Luxembourg (Western Europe) and the outcome, both in relation to the different histological types, were analysed., Methods: The population-based files of the Morphologic Tumour Registry collecting at a nation-wide level all testicular cancers diagnosed between 1980 and 2004 in the central department of pathology in Luxembourg were retrospectively reviewed. In addition, the presence of concomitant malignant diseases was investigated., Results: 397 patients with GCT were evaluated. The mean age was 33.7 years (range: 1-72). Most of the patients (58.7%) were between 15 and 34 years of age. The age-standardized incidence rates rose from 4.5 per 10(5) (1980-1984) to 7.7 per 10(5) (2000-2004). Out of 275 (69.3%) pure GCTs, 218 seminomas, 48 embryonal carcinomas, 4 yolk sac tumours, 4 malignant teratomas and 1 choriocarcinoma were identified. 30.7% GCTs were of mixed type with 17 different histological variants. 5.8% of the patients had metachronous concomitant cancers, 2% bilateral GCTs and 3.8% non-testicular neoplasms. In all histological categories, with the exception of the pure seminomas, prognosis was determined within the 24 months following diagnosis; pure seminomas need long time follow-up. Ten-year observed survival rates exceeded mostly 90%. Pure embryonal carcinomas had the worst prognosis with a 10-year observed survival rate of 87.1 +/- 12%., Conclusions: Testicular germ cell tumours are rare, highly curable neoplasms that generally occur in young patients. In all histological categories, except for pure seminomas, prognosis was determined within the 24 months after diagnosis. Despite better observed survival rates, patients with pure seminomas, without or with metachronous concomitant non-testicular malignancies, need long time followup strategy.

In most cases, renal graft obstruction is caused by ureteral stenosis due to ischemia or technical error. Exceptional cases have been published where the obstacle was the result of incarceration of the ureter in an inguinal hernia. We report a case of this type, which prompt assessment was possible due to ultrasound and magnetic resonance imaging with 3D reconstruction.

Complete resection of malignant glioblastomas is usually impossible because of diffuse and widespread invasion of tumor cells, and complementary approaches need to be developed in order to improve the efficacy of current treatments. Consumption of fruits and berries has been associated with decreased risk of developing cancer and there is great interest in the use of molecules from dietary origin to improve anticancer therapies. In this work, we report that the aglycons of the most abundant anthocyanins in fruits, cyanidin (Cy), delphinidin (Dp), and petunidin (Pt), act as potent inhibitors of glioblastoma cell migration. Dp clearly exhibited the highest inhibitory potency, this effect being related to the ortho-dihydroxyphenyl structure on the B-ring and the presence of a free hydroxyl group at position 3. Dp decreases the expression of both urokinase-type plasminogen activator receptor (uPAR) and the low-density lipoprotein receptor-related protein (LRP), acting at the transcriptional levels. In addition, Dp upregulated urokinase-type plasminogen activator (uPA) and downregulated the plasminogen activator inhibitor-1 (PAI-1) but decreased, in a concentration-dependent manner, the uPA-dependent conversion of plasminogen to plasmin, indicating that the upregulation of uPA observed with these compounds was not associated with induction of the plasminolytic activity. Overall, these results demonstrate that Dp, Pt, and Cy affect plasminogen activation, thus leading to the inhibition of glioblastoma cell migration and therefore they may be helpful for the development of new strategies for cancer prevention and therapy., (2006 Wiley-Liss, Inc.)

Epidemiological studies have shown that a diet rich in fruits and vegetables has a beneficial preventive effect on cardiovascular diseases and cancer by mechanisms that have not yet been elucidated. In this work, we investigated the antiangiogenic activities of anthocyanidins, a class of polyphenols present at high levels in fruits. Among the tested anthocyanidins (cyanidin, delphinidin, malvidin, pelargonidin, peonidin and petunidin), delphinidin was the most potent angiogenic inhibitor. In vitro, low concentrations of delphinidin inhibited vascular endothelial growth factor (VEGF)-induced tyrosine phosphorylation of VEGF receptor (VEGFR)-2, leading to the inhibition of downstream signaling triggered by VEGFR-2. Inhibition of VEGFR-2 by delphinidin inhibited the VEGF-induced activation of ERK-1/2 signaling and the chemotactic motility of human EC as well as their differentiation into capillary-like tubular structures in Matrigel and within fibrin gels. In vivo, delphinidin was able to suppress basic fibroblast growth factor-induced vessel formation in the mouse Matrigel plug assay. The identification of delphinidin as a naturally occurring inhibitor of VEGF receptors suggests that this molecule possesses important antiangiogenic properties that may be helpful for the prevention and treatment of cancer.

We have previously observed that the synthetic peptide corresponding to amino acids 31-45 (PCK3145) of PSP94 can reduce prostate tumor growth in vivo. Moreover, a recently concluded phase IIa clinical trial with patients with hormone refractory prostate cancer indicated that PCK3145 down-regulates the levels of plasma matrix metalloproteinase (MMP)-9, a MMP involved in metastasis and tumor angiogenesis. The purpose of our study was to investigate the molecular mechanisms of action of PCK3145 and whether this peptide could antagonize tumor neovascularization. We show that, in a syngeneic in vivo model of rat prostate cancer, the expression of endothelial cell (EC) specific CD31, a marker of tumor vessel density, was decreased by 43% in PCK3145-treated animals. In vitro, PCK3145 specifically antagonized in a dose-dependent manner the VEGF-induced ERK phosphorylation as well as the phosphorylation of the VEGFR-2 in cultured EC (HUVEC). These anti-VEGF effects were partly reproduced by pharmacological inhibitors such as PD98059 and PTK787, suggesting that PCK3145 inhibits the tyrosine kinase activity associated to VEGFR-2, which in turn prevents intracellular signalling through the MAPK cascade. Moreover, PCK3145 was also found to inhibit the PDGF-induced phosphorylation of PDGFR in smooth muscle cells. Finally, PCK3145 inhibited in vitro EC tubulogenesis and VEGF-induced MMP-2 secretion suggesting its potential implication as an antiangiogenic agent. Our study demonstrates that PCK3145 interferes with the tyrosine kinase activity associated with VEGF signalling axis in EC. The antiangiogenic properties of this peptide could be highly beneficial and exploited in novel antiangiogenic therapies, for patients with various cancers., (2005 Wiley-Liss, Inc.)

Short-term reactions of young turkeys to changes in the physical characteristics of their feed sometimes give rise to problems of adaptation in the field. Specific feeders were designed for this study to automatically count the number of pecks given at feed by 4-wk-old male turkeys during 95-min sessions. The lighting program was intermittent (0140L:0100D). In experiment 1, 4 series of 12 birds were tested 4 times/day from 28 to 31 d of age. Four control turkeys were consistently tested with 1 feed, and 8 experimental turkeys ate 1 of 32 commercial feeds (30 as pellets and 2 as crumbs) with a distinct feed for each test (16 replicates/experimental feed). Feed intake, total number of pecks, and pecking efficiency (mg/peck) were recorded for each test and normalized for each turkey. The effects of series, day, and test were not significant for controls. The number of pecks and pecking efficiency differed among feeds (P < 0.001) but not feed intake. Hierarchical Cluster Analysis for these variables distinguished 3 groups of feed: group 3 (6 crumb and small pellets) resulted in high pecking and low efficiency. However, group 1 (10 feeds) were pecked at less but more efficiently than group 2 (16 feeds) for similar feed intake, although the average sizes of the pellets were similar (6.23 and 6.16 mm, respectively), as were the average bulk density, hardness, resistance to abrasion, and color characteristics of the pellets for both groups. Two feeds of each of these 2 groups were compared in a second experiment for 12 turkeys receiving the 4 feeds successively each day over 4 d in varying order. The turkeys consistently pecked the feeds of group 1 less and less efficiently compared with group 2. The automated measurement of pecking, combined with a more detailed image analysis of feed particles, might enhance the evaluation of the effects of feed technology on the behavior of turkeys and thus become a useful tool for the feed industry.

Vascular endothelial growth factor (VEGF) and platelet-derived lipid sphingosine-1-phosphate (S1P) are two proinflammatory mediators which contribute to angiogenesis, in part through the synthesis of platelet-activating factor (PAF). The red grape skin polyphenolic extract (SGE) both prevents and inhibits angiogenesis in the Matrigel model, decreases the basal motility of endothelial and cancer cells, and reverses the chemotactic effect of S1P and VEGF on bovine aortic endothelial cells (BAECs) as well as the chemotactic effect of conditioned medium on human HT-1080 fibrosarcoma, human U-87 glioblastoma, and human DAOY medulloblastoma cells. Inhibition of VEGF- and S1P-mediated chemotaxis by SGE is associated with a down-regulation of ERK and p38/MAPK phosphorylation and a decreased in acute PAF synthesis. Notably, as do extracellular inhibitors of PAF receptor, SGE prevents S1P-induced PAF synthesis and the resulting activation of the S1P/endothelial differentiation gene-1 cascade. Given the key role of VEGF and S1P in inflammation, angiogenesis, and tumor invasion, SGE may therefore contribute to prevent (or to delay) the development of diseases associated with angiogenesis dysregulation, including cancer. The dual inhibition of S1P- and VEGF-mediated migration of endothelial cell and of serum-stimulated migration of U-87 cells suggests a usefulness of SGE against highly invasive human glioblastoma.

We present a case of inguinal bladder hernia detected initially with sonography in an adult patient. Compared with digestive or omental hernias, inguinocrural bladder herniations are a rarer occurrence (1 to 4% of all cases). Their detection is nevertheless highly imperative in order to avoid inadvertent injury to the bladder during routine hemiorrhaphy. Since the advent of high frequency equipment, ultrasonography has become the essential method of diagnosing vesical hernias. It is simple and fast, totally non-invasive, inexpensive, and widely available.

The vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptors play essential and complementary roles in angiogenesis and combined inhibition of these receptors has been shown to result in potent antitumor activity in vivo. In this study, we report that ellagic acid (EA), a natural polyphenol found in fruits and nuts, inhibits VEGF-induced phosphorylation of VEGFR-2 in endothelial cell (EC) as well as PDGF-induced phosphorylation of PDGFR in smooth muscle cells, leading to the inhibition of downstream signaling triggered by these receptors. EA also specifically inhibited VEGF-induced migration of ECs as well as their differentiation into capillary-like tubular structures and abolished PDGF-dependent smooth muscle cell migration. Interestingly, EA presents a greater selectivity for normal cells than for tumor cells since the migration of the U87 and HT1080 cell lines were much less affected by this molecule. The identification of EA as a naturally occurring dual inhibitor of VEGF and PDGF receptors suggests that this molecule possesses important antiangiogenic properties that may be helpful for the prevention and treatment of cancer.

Objective: This study aimed to estimate the lifetime frequency of suicide attempts in a large referred population of women with DSM-IV bulimia nervosa (BN), and to compare demographic and clinical characteristics of those who had attempted suicide and those who had not., Method: A total of 295 women (202 with BN purging type, 68 with BN non-purging type and 25 with anorexia nervosa binge/eating purging type) were assessed using a semi-structured interview and self-rated questionnaires., Results: Suicide attempts were frequent (27.8% of women), often serious and/or multiple. Women who had attempted suicide differed significantly from those who had not for earlier onset of psychopathology, higher severity of depressive and general symptoms, and more impulsive disordered conducts, but not for the core symptoms or severity of BN., Conclusion: Interventions targeting depressive and impulsive features associated with BN are essential to reduce the risk of suicide attempt in women with this disorder.

The concept of cancer prevention by use of naturally occuring substances that could be included in the diet is under investigation as a practical approach towards reducing cancer incidence, and therefore the mortality and morbidity associated with this disease. Tea, which is the most popularly consumed beverage aside from water, has been particularly associated with decreased risk of various proliferative diseases such as cancer and atherosclerosis in humans. Various studies have provided evidence that polyphenols are the strongest biologically active agents in green tea. Green tea polyphenols (GTPs) mainly consist of catechins (3-flavanols), of which (-)-epigallocatechin gallate is the most abundant and the most extensively studied. Recent observations have raised the possibility that green tea catechins, in addition to their antioxidative properties, also affect the molecular mechanisms involved in angiogenesis, extracellular matrix degradation, regulation of cell death and multidrug resistance. This article will review the effects and the biological activities of green tea catechins in relation to these mechanisms, each of which plays a crucial role in the development of cancer in humans. The extraction of polyphenols from green tea, as well as their bioavailability, are also discussed since these two important parameters affect blood and tissue levels of the GTPs and consequently their biological activities. In addition, general perspectives on the application of dietary GTPs as novel antiangiogenic and antitumor compounds are also presented.

Purpose: Vascular endothelial growth factor (VEGF) is a potent regulator of angiogenesis, which exerts direct effects on vascular endothelial cells, including endothelial cell proliferation and survival, tubulogenesis, and vascular permeability. In this study, we examined whether Neovastat, a naturally occurring multifunctional antiangiogenic drug, could inhibit the endothelial cell response to VEGF stimulation., Results: We demonstrated that Neovastat was able to block the VEGF-dependent microvessel sprouting from Matrigel-embedded rat aortic rings, and it also blocked the VEGF-induced endothelial cell tubulogenesis in vitro. In vivo studies showed that Neovastat was able to specifically inhibit VEGF-induced plasma extravasation in numerous tissues, including pancreas and skin. The mechanism of action of Neovastat on VEGF-mediated effects was also evaluated at the molecular level. Neovastat was shown to compete against the binding of VEGF to its receptor in endothelial cells and significantly inhibited the VEGF-dependent tyrosine phosphorylation of VEGF receptor-2, whereas it had no significant effect on VEGF receptor-1 activity. Moreover, the inhibition of receptor phosphorylation was correlated with a marked decrease in the ability of VEGF to induce pERK activation. Neovastat does not compete against the binding of basic fibroblast growth factor, indicating a preferential inhibitory effect on the VEGF receptor., Conclusions: Because Neovastat was shown previously to inhibit metalloproteinase activities, these results suggest that Neovastat is able to target multiple steps in tumor neovascularization, further emphasizing its use as a pleiotropic, multifunctional antiangiogenic drug.

Vascular endothelial growth factor (VEGF) receptors (VEGFR) play a major role in tumor angiogenesis and, thus, represent attractive targets for the development of novel anticancer therapeutics. In this work, we report that green tea catechins are novel inhibitors of VEGFR-2 activity. Physiological concentrations (0.01-1 microM) of epigallocatechin-3 gallate, catechin-3 gallate, and, to a lesser extent, epicatechin-3 gallate induce a rapid and potent inhibition of VEGF-dependent tyrosine phosphorylation of VEGFR-2. The inhibition of VEGFR-2 by epigallocatechin-3 gallate was similar to that induced by Semaxanib (SU5416), a specific VEGFR-2 inhibitor. The inhibition of VEGFR-2 activity by the catechins displayed positive correlation with the suppression of in vitro angiogenesis. These observations suggest that the anticancer properties of green tea extracts may be related to their inhibition of VEGF-dependent angiogenesis.