Prostate Cancer Unit Initiative in Europe: A position paper by the European School of Oncology.

The Prostate Cancer Programme of the European School of Oncology developed the concept of specialised interdisciplinary and multiprofessional prostate cancer care to be formalized in Prostate Cancer Units (PCU). After the publication in 2011 of the collaborative article "The Requirements of a Specialist Prostate Cancer Unit: A Discussion Paper from the European School of Oncology", in 2012 the PCU Initiative in Europe was launched. A multiprofessional Task Force of internationally recognized opinion leaders, among whom representatives of scientific societies, and patient advocates gathered to set standards for quality comprehensive prostate cancer care and designate care pathways in PCUs. The result was a consensus on 40 mandatory and recommended standards and items, covering several macro-areas, from general requirements to personnel to organization and case management. This position paper describes the relevant, feasible and applicable core criteria for defining PCUs in most European countries delivered by PCU Initiative in Europe Task Force.

Evolving characteristics and outcome of secondary acute promyelocytic leukemia (APL): A prospective analysis by the French-Belgian-Swiss APL group.

BACKGROUND: Reports of patients with secondary acute promyelocytic leukemia (APL) have increased in recent years, particularly for those who received treatment with mitoxantrone, and retrospective studies have suggested that their characteristics and outcomes were similar to those of patients with de novo APL. METHODS: The authors investigated patients with de novo and secondary APL who were included in the ongoing APL-2006 trial. Patients with secondary APL who were included in that trial also were compared with a previous retrospective cohort of patients with secondary APL. RESULTS: In the APL-2006 trial, 42 of 280 patients (15%) had secondary APL. Compared with the retrospective cohort, patients with secondary APL in the APL-2006 trial had a lower incidence of prior breast carcinoma (35.7% vs 57%; P = .03) and a higher incidence of prior prostate carcinoma (26.2% vs 4.7%; P < .001). Treatment of the primary tumor in the APL-2006 trial less frequently included combined radiochemotherapy (28.6% vs 47.2%; P = .044) and no mitoxantrone (0% vs 46.7%; P = .016) but more frequently included anthracyclines (53.3% vs 38.3%; P = .015). In the APL-2006 trial, patients who had secondary APL, compared with those who had de novo APL, were older (mean, 60.2 years vs 48.7 years, respectively; P < .0001) but had a similar complete response rate (97.6% vs 90.3%, respectively), cumulative incidence of relapse (0% vs 1.8%, respectively), and overall survival (92.3% vs 90.9%, respectively) at 18 months. CONCLUSIONS: Although the incidence of secondary APL appears to be stable over time, evolving strategies for the treatment of primary cancers have reduced its occurrence among breast cancer patients but have increased its incidence among patients with prostate cancer. The current results confirm prospectively that patients with secondary APL have characteristics and outcomes similar to those of patients with de novo APL. Cancer 2015;121:2393-2399. © 2015 American Cancer Society.

The activity of the anti-apoptotic fragment generated by the caspase-3/p120 RasGAP stress-sensing module displays strict Akt isoform specificity.

The caspase-3/p120 RasGAP module acts as a stress sensor that promotes pro-survival or pro-death signaling depending on the intensity and the duration of the stressful stimuli. Partial cleavage of p120 RasGAP generates a fragment, called fragment N, which protects stressed cells by activating Akt signaling. Akt family members regulate many cellular processes including proliferation, inhibition of apoptosis and metabolism. These cellular processes are regulated by three distinct Akt isoforms: Akt1, Akt2 and Akt3. However, which of these isoforms are required for fragment N mediated protection have not been defined. In this study, we investigated the individual contribution of each isoform in fragment N-mediated cell protection against Fas ligand induced cell death. To this end, DLD1 and HCT116 isogenic cell lines lacking specific Akt isoforms were used. It was found that fragment N could activate Akt1 and Akt2 but that only the former could mediate the protective activity of the RasGAP-derived fragment. Even overexpression of Akt2 or Akt3 could not rescue the inability of fragment N to protect cells lacking Akt1. These results demonstrate a strict Akt isoform requirement for the anti-apoptotic activity of fragment N.

Redox Signaling by the RNA Polymerase III TFIIB-Related Factor Brf2.

TFIIB-related factor 2 (Brf2) is a member of the family of TFIIB-like core transcription factors. Brf2 recruits RNA polymerase (Pol) III to type III gene-external promoters, including the U6 spliceosomal RNA and selenocysteine tRNA genes. Found only in vertebrates, Brf2 has been linked to tumorigenesis but the underlying mechanisms remain elusive. We have solved crystal structures of a human Brf2-TBP complex bound to natural promoters, obtaining a detailed view of the molecular interactions occurring at Brf2-dependent Pol III promoters and highlighting the general structural and functional conservation of human Pol II and Pol III pre-initiation complexes. Surprisingly, our structural and functional studies unravel a Brf2 redox-sensing module capable of specifically regulating Pol III transcriptional output in living cells. Furthermore, we establish Brf2 as a central redox-sensing transcription factor involved in the oxidative stress pathway and provide a mechanistic model for Brf2 genetic activation in lung and breast cancer.

Hollywood Films in the Non-Western World: What Are the Criteria Followed by the Chinese Government When Choosing Hollywood Film Imports?

This dissertation argues that the Government of the People’s Republic of China, when it made the decision to import a quota of Hollywood films in 1994 to revive the failing domestic film industry, had different possible criteria in mind. This project has studied four of them: first, importing films that gave a negative image of the United States; second, importing films that featured Chinese talent or themes; third, importing films that were box office hits in the United States; and fourth, importing films with a strong technological innovation ingredient. In order to find out the most important criteria for the Chinese Government, this dissertation offers a dataset that analyzes a population of 262 Hollywood films released in the PRC between 1994 and 2010. For each unit, a method has been developed to compile data that will determine whether the film reflects any of the four criteria, and findings in the form of yearly percentages have been drawn. Results show that, out of the four studied criteria, the two predominant reasons for China to import films were technological innovation and box office hits. This tells us that, at this point, the Chinese Government shows more interest in obtaining big revenues and learning from technically innovative American films than in delivering underlying political messages. This dissertation contributes to the existing literature by analyzing the content of all the films imported by China between 1994 and 2010, while integrating in the analysis variables based on the existing knowledge.

Persistent spatial clusters of high body mass index in a Swiss urban population as revealed by the 5-year GeoCoLaus longitudinal study.

OBJECTIVE: Body mass index (BMI) may cluster in space among adults and be spatially dependent. Whether and how BMI clusters evolve over time in a population is currently unknown. We aimed to determine the spatial dependence of BMI and its 5-year evolution in a Swiss general adult urban population, taking into account the neighbourhood-level and individual-level characteristics. DESIGN: Cohort study. SETTING: Swiss general urban population. PARTICIPANTS: 6481 georeferenced individuals from the CoLaus cohort at baseline (age range 35-74 years, period=2003-2006) and 4460 at follow-up (period=2009-2012). OUTCOME MEASURES: Body weight and height were measured by trained healthcare professionals with participants standing without shoes in light indoor clothing. BMI was calculated as weight (kg) divided by height squared (m(2)). Participants were geocoded using their postal address (geographic coordinates of the place of residence). Getis-Ord Gi statistic was used to measure the spatial dependence of BMI values at baseline and its evolution at follow-up. RESULTS: BMI was not randomly distributed across the city. At baseline and at follow-up, significant clusters of high versus low BMIs were identified and remained stable during the two periods. These clusters were meaningfully attenuated after adjustment for neighbourhood-level income but not individual-level characteristics. Similar results were observed among participants who showed a significant weight gain. CONCLUSIONS: To the best of our knowledge, this is the first study to report longitudinal changes in BMI clusters in adults from a general population. Spatial clusters of high BMI persisted over a 5-year period and were mainly influenced by neighbourhood-level income.

Predation on common tern eggs by the yellow-legged gull at the Ebro Delta

The Ebro Delta holds a large seabird community, including a common tern (Sterna hirundo) local population of 3,085 pairs in 2000 which breeds scattered in several colonies. At El Canalot colony, 1,178 (1999) and 1,156 pairs (2000) of this species bred distributed in 32 and 38 sub-colonies respectively. These sub-colonies varied in size from 1 to 223 pairs and were placed near the main breeding colonies of yellow-legged gulls (Larus cachinnans) and Audouin´s gulls (L. audouinii), which are potential egg-predators of terns. We studied egg predation during 1999 (6 sub-colonies) and 2000 (27 sub-colonies). Overall, we found that 10.6% of the nests in 1999 and 16.7% in 2000 suffered partial or total egg predation, being total in 81.1% of the predatory events. Predation was significantly higher in small sub-colonies (< 11 pairs): 49.4% in 1999 and 75.5% in 2000. Only attacks from yellow-legged gulls were observed, and defence behaviour of terns was significantly more frequent against this gull species (40.5 hours of observation), suggesting that in most cases the egg predation recorded was due to this species. Probability of egg predation was significantly and negatively correlated with distance to the nearest yellow-legged gull sub-colony, although this relationship was no more significant after adjustment for sub-colony size. On the other hand, distance to the nearest Audouin´s gull sub-colony did not show any effect. Our results suggest that the impact of large gulls (at least yellow-legged gulls) upon smaller seabirds breeding in the area might be important, especially when they are breeding in small sub-colonies. Further studies are needed to analyse the general impact of large gulls upon the breeding populations of other colonial bird species in the area.

Prise en charge de la candidose oesophagienne en médecine de premier recours [Management of the esophageal candidiasis by the primary care physician].

La candidose oesophagienne est l'une des infections opportunistes les plus fréquentes chez les patients infectés par le VIH. Ce diagnostic se rencontre également chez des patients sans immunodéficience manifeste. Certains facteurs de risque sont également associés à cette pathologie, tels que les traitements corticoïdes systémiques et inhalés ou les traitements par inhibiteurs de la pompe à protons et les antihistaminiques H2. En l'absence de facteur de risque identifié, un déficit immunitaire primaire devrait être recherché. La prévention de la candidose oesophagienne est basée en premier lieu sur l'identification des facteurs de risque, ainsi qu'un meilleur contrôle de ceux-ci. Cet article présente en détail la physio-pathologie, la clinique et la prise en charge par le médecin de premier recours de la candidose oesophagienne. Nous aborderons également les moyens de prévention de la candidose oesophagienne quand il y a lieu. Esophageal candidiasis is one of the most common opportunistic infections in patients infected by human immunodeficiency virus (HIV). This pathology is also found in patients without overt immunodeficiency. Other risk factors are known to be associated with this disease like inhaled or systemic corticosteroid treatment or proton-pump inhibitors and H2 receptor antagonists. In the absence of identified risk factors, a primary immune deficiency should be sought. Prevention of esophageal candidiasis is based primarily on the identification of risk factors, and a better control of them. This article presents a review of the physiopathology, clinical presentation and management of esophageal candidiasis by primary care physicians. We will also discuss ways of preventing esophageal candidiasis when necessary.

Differential regulation of horizontally acquired and core genome genes by the bacterial modulator H-NS

Horizontal acquisition of DNA by bacteria dramatically increases genetic diversity and hence successful bacterial colonization of several niches, including the human host. A relevant issue is how this newly acquired DNA interacts and integrates in the regulatory networks of the bacterial cell. The global modulator H-NS targets both core genome and HGT genes and silences gene expression in response to external stimuli such as osmolarity and temperature. Here we provide evidence that H-NS discriminates and differentially modulates core and HGT DNA. As an example of this, plasmid R27-encoded H-NS protein has evolved to selectively silence HGT genes and does not interfere with core genome regulation. In turn, differential regulation of both gene lineages by resident chromosomal H-NS requires a helper protein: the Hha protein. Tight silencing of HGT DNA is accomplished by H-NS-Hha complexes. In contrast, core genes are modulated by H-NS homoligomers. Remarkably, the presence of Hha-like proteins is restricted to the Enterobacteriaceae. In addition, conjugative plasmids encoding H-NS variants have hitherto been isolated only from members of the family. Thus, the H-NS system in enteric bacteria presents unique evolutionary features. The capacity to selectively discriminate between core and HGT DNA may help to maintain horizontally transmitted DNA in silent form and may give these bacteria a competitive advantage in adapting to new environments, including host colonization.

Differential regulation of horizontally acquired and core genome genes by the bacterial modulator H-NS

Horizontal acquisition of DNA by bacteria dramatically increases genetic diversity and hence successful bacterial colonization of several niches, including the human host. A relevant issue is how this newly acquired DNA interacts and integrates in the regulatory networks of the bacterial cell. The global modulator H-NS targets both core genome and HGT genes and silences gene expression in response to external stimuli such as osmolarity and temperature. Here we provide evidence that H-NS discriminates and differentially modulates core and HGT DNA. As an example of this, plasmid R27-encoded H-NS protein has evolved to selectively silence HGT genes and does not interfere with core genome regulation. In turn, differential regulation of both gene lineages by resident chromosomal H-NS requires a helper protein: the Hha protein. Tight silencing of HGT DNA is accomplished by H-NS-Hha complexes. In contrast, core genes are modulated by H-NS homoligomers. Remarkably, the presence of Hha-like proteins is restricted to the Enterobacteriaceae. In addition, conjugative plasmids encoding H-NS variants have hitherto been isolated only from members of the family. Thus, the H-NS system in enteric bacteria presents unique evolutionary features. The capacity to selectively discriminate between core and HGT DNA may help to maintain horizontally transmitted DNA in silent form and may give these bacteria a competitive advantage in adapting to new environments, including host colonization.

Educational resources offered by the European Board of Physical and Rehabilitation Medicine (EBPRM)

Background .- Physical and Rehabilitation Medicine (PRM) is a very demanding medical speciality. To ensure high standard of research and care in PRM all across Europe, it is crucial to attract gifted trainees and offer them high quality education. At undergraduate level, many medical schools in Europe omit to offer teaching on disabled persons and on basic PRM knowledge. Thus PRM is hardly known to medical students. For postgraduate trainees access to evidence-based knowledge as well as teaching of research methodology specific to PRM, rehabilitation methodology, disability management and team building also need to be strengthened to increase the visibility of PRM. Action .- To address these issues the EBPRM proposes presently a specific undergraduate curriculum in PRM including the issues of disability, participation and handicap as a basis for general medical practice and postgraduate rehabilitation training. For PRM trainees many educational documents are now available on the EBPRM website. A growing number of educational sessions for PRM trainees take place during international and national PRM Congresses which can be accessed at low cost. Educational papers published regularly in European rehabilitation journals and European PRM Schools are offered free or at very low cost to trainees.

Mycorrhization between Cistus ladanifer L. and Boletus edulis Bull is enhanced by the mycorrhiza helper bacteria Pseudomonas fluorescens Migula.

Boletus edulis Bull. is one of the most economically and gastronomically valuable fungi worldwide. Sporocarp production normally occurs when symbiotically associated with a number of tree species in stands over 40 years old, but it has also been reported in 3-year-old Cistus ladanifer L. shrubs. Efforts toward the domestication of B. edulis have thus focused on successfully generating C. ladanifer seedlings associated with B. edulis under controlled conditions. Microorganisms have an important role mediating mycorrhizal symbiosis, such as some bacteria species which enhance mycorrhiza formation (mycorrhiza helper bacteria). Thus, in this study, we explored the effect that mycorrhiza helper bacteria have on the efficiency and intensity of the ectomycorrhizal symbiosis between C. ladanifer and B. edulis. The aim of this work was to optimize an in vitro protocol for the mycorrhizal synthesis of B. edulis with C. ladanifer by testing the effects of fungal culture time and coinoculation with the helper bacteria Pseudomonas fluorescens Migula. The results confirmed successful mycorrhizal synthesis between C. ladanifer and B. edulis. Coinoculation of B. edulis with P. fluorescens doubled within-plant mycorrhization levels although it did not result in an increased number of seedlings colonized with B. edulis mycorrhizae. B. edulis mycelium culture time also increased mycorrhization levels but not the presence of mycorrhizae. These findings bring us closer to controlled B. edulis sporocarp production in plantations.