Circulating Biomarkers in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma Treated With Everolimus in the Pre-nephrectomy Setting.

Many drugs are available in renal cell carcinoma (RCC), yet clinicians are still looking for predictive biomarkers of disease recurrence or progression supporting more personalised treatments. An assessment of circulating biomarkers over time was carried out in this French, open-label, single-arm, multicentre trial conducted in 25 patients with either locally advanced (n = 14) or metastatic RCC (n = 11) who received everolimus (10 mg daily) for 6 weeks prior to nephrectomy (NEORAD, NCT01715935). Circulating biomarkers, including circulating tumour cells, haematopoietic and endothelial cells, plasma angiogenesis and inflammatory markers were quantified at baseline, upon everolimus and post-nephrectomy. We assessed tumour burden, objective response rate upon RECIST1.1, disease-free survival (DFS) and progression-free survival (PFS). The correlation between circulating biomarkers was evaluated with multiple factor analysis and biomarker association with DFS/PFS by Cox regression. No objective response rate was obtained before nephrectomy. Upon everolimus, neutrophils, platelets and sVEGFR2 significantly decreased. We did not find any association between circulating biomarkers and DFS/PFS, but patients with the highest tumour burden at baseline had significantly higher plasma levels of interleukin-6, an inflammatory circulating biomarker, and lower levels of sVEGFR2, related to angiogenesis. Further understanding of the link between these circulating biomarkers could help to optimise drug combinations in RCC.

Microbiological assessment of arterial allografts processed in a tissue bank.

The transmission of microbial infection through tissue allografts is one of the main risks that must be controlled in tissue banks. Therefore, microbiological monitoring controls and validated protocols for the decontamination of tissues during processing have been implemented. This study is based on the evaluation of data from microbiological cultures of arteries (mainly long peripheral arteries) processed in the tissue bank of Valencia (Spain). Donors' profile, pre- and post-disinfection tissue samples were assessed. The presence of residual antibiotics in disinfected tissues was determined and the antimicrobial potential of these tissues was tested. Our overall contamination rate was 23.69%, with a disinfection rate (after antibiotic incubation) of 87.5%. Most (76.09%) of the microbial contaminants were identified as Gram positive. Arterial allografts collected from body sites affected by prior organ removal showed higher risk of contamination. Only vancomycin was detected as tissue release. The antimicrobial effect on Candida albicans was lower than that for bacterial species. Risk assessment for microbial contamination suggested the donor's skin and the environment during tissue collection as the main sources for allograft contamination. Antibiotic-disinfected arterial allografts showed antimicrobial potential.

[A complex case of miliary pulmonary tuberculosis following intravesical BCG therapy]. / Un cas complexe de miliaire pulmonaire post-BCG thérapie pour carcinome urothélial.

Bladder cancer (urothelial carcinoma in 90 % of cases) is the most common neoplasia of the urinary tract. Superficial carcinoma represents 70-80 % of bladder cancers. The treatment of these tumours includes, after transuretral resection, intravesical Bacillus Calmette-Guerin (BCG) instillation therapy. This treatment constitutes, by its immune-mediated anti-tumoral action, the first step of immunotherapy in cancer. Severe complications (granulomatosis, hypersensitivity pneumonitis or orchitis) are rare (0.5-2 %). Here we report a complex case of pulmonary granulomatosis secondary to BCG therapy. This is a 74-year-old male, treated for superficial bladder carcinoma by transuretral resection (pT1G3) and then endovesical instillations of BCG therapy for two months. Two years later, a new transuretral resection shows an infiltrating urothelial carcinoma pT2G3. The extension balance finds a persistent micro-nodular pulmonary infiltrate. A broncho-alveolar lavage is then realised but no mycobacteria was found. A surgical biopsy of a nodule is performed and revealed a histiocytic reaction without any neoplastic element. Detection of Mycobacterium tuberculosis by Polymerase Chain Reaction (PCR) was finally positive. In the absence of a secondary lesion, the patient had a cysto-prostatectomy and began a tritherapy against tuberculosis. Post-BCG therapy granulomatosis is a rare complication but should remain a differential diagnosis in front of the appearance of pulmonary nodes in patients who have received posttransuretral resection BCG instillations. Mycobacterial DNA PCR research remains the most sensitive examination.

Les carcinomes urothéliaux superficiels de vessies représentent 70 à 80 % des tumeurs de la vessie. Leur traitement comprend, après résection transurétrale, une BCG (Bacille de Calmette et Guérin) thérapie par instillations endovésicales. Les complications sévères (granulomatose, pneumopathie d'hypersensibilité ou orchite) sont rares (0,5-2 %) mais nous rapportons ici un cas complexe de granulomatose pulmonaire secondaire à une BCG thérapie. Il s'agit d'un homme de 74 ans, traité pour un carcinome urothélial superficiel de vessie par résection endo-urétrale (pT1G3) puis instillations endovésicales de BCG thérapie. Deux années après, une nouvelle résection transurétrale objective un carcinome urothélial infiltrant pT2G3. Le bilan d'extension retrouve un infiltrat pulmonaire micronodulaire persistant. Un lavage bronchoalvéolaire ne retrouve pas de bacilles acido-alcoolo-résistants. La biopsie chirurgicale d'un nodule retrouve une réaction histiocytaire sans élément néoplasique. La Polymerase Chain Reaction (PCR) à la recherche de mycobactérie du groupe tuberculosis revient finalement positive. En l'absence de lésion secondaire, le patient a bénéficié d'une cystoprostatectomie et a débuté dans les suites une trithérapie antituberculeuse. La granulomatose post-BCG thérapie est une complication rare, mais doit rester un diagnostic différentiel devant l'apparition de micronodules pulmonaires chez les patients ayant reçu des instillations de BCG post-résection transurétrale. La recherche par PCR d'ADN de mycobactéries reste l'examen le plus sensible.

Bleeding risk of terminally ill patients hospitalized in palliative care units: the RHESO study.

Essentials Bleeding incidence as hemorrhagic risk factors are unknown in palliative care inpatients. We conducted a multicenter observational study (22 Palliative Care Units, 1199 patients). At three months, the cumulative incidence of clinically relevant bleeding was 9.8%. Cancer, recent bleeding, thromboprophylaxis and antiplatelet therapy were independent risk factors. SUMMARY: Background The value of primary thromboprophylaxis in patients admitted to palliative care units is debatable. Moreover, the risk of bleeding in these patients is unknown. Objectives Our primary aim was to assess the bleeding risk of patients in a real-world practice setting of hospital palliative care. Our secondary aim was to determine the incidence of symptomatic deep vein thrombosis and to identify risk factors for bleeding. Patients/Methods In this prospective, observational study in 22 French palliative care units, 1199 patients (median age, 71 years; male, 45.5%), admitted for the first time to a palliative care unit for advanced cancer or pulmonary, cardiac or neurologic disease were included. The primary outcome was adjudicated clinically relevant bleeding (i.e. a composite of major and clinically relevant non-major bleeding) at 3 months. The secondary outcome was symptomatic deep vein thrombosis. Results The most common reason for palliative care was cancer (90.7%). By 3 months, 1087 patients (91.3%) had died and 116 patients had presented at least one episode of clinically relevant bleeding (fatal in 23 patients). Taking into account the competing risk of death, the cumulative incidence of clinically relevant bleeding was 9.8% (95% confidence interval [CI], 8.3-11.6). Deep vein thrombosis occurred in six patients (cumulative incidence, 0.5%; 95% CI, 0.2-1.1). Cancer, recent bleeding, antithrombotic prophylaxis and antiplatelet therapy were independently associated with clinically relevant bleeding at 3 months. Conclusions Decisions regarding the use of thromboprophylaxis in palliative care patients should take into account the high risk of bleeding in these patients.

Epicure: a European epidemiological study of patients with an advanced or metastatic Urothelial Carcinoma (UC) having progressed to a platinum-based chemotherapy.

BACKGROUND: Platinum-based systemic chemotherapy is considered the backbone for management of advanced urothelial carcinomas. However there is a lack of real world data on the use of such chemotherapy regimens, on patient profiles and on management after treatment failure. METHODS: Fifty-one randomly selected physicians from 4 European countries registered 218 consecutive patients in progression or relapse following a first platinum-based chemotherapy. Patient characteristics, tumor history and treatment regimens, as well as the considerations of physicians on the management of urothelial carcinoma were recorded. RESULTS: A systemic platinum-based regimen had been administered as the initial chemotherapy in 216 patients: 15 in the neoadjuvant setting, 61 in adjuvant therapy conditions, 137 in first-line advanced setting and 3 in other conditions. Of these patients, 76 (35 %) were initially considered as cisplatin-unfit, mainly because of renal impairment (52 patients). After platinum failure, renal impairment was observed in 44 % of patients, ECOG Performance Status ≥ 2 in 17 %, hemoglobinemia < 10 g/dL in 16 %, hepatic metastases in 13 %. 80 % of these patients received further anticancer therapy. Immediately after failure of adjuvant/neoadjuvant chemotherapy, most subsequent anticancer treatments were chemotherapy doublets (35/58), whereas after therapy failure in the advanced setting most patients receiving further anticancer drugs were treated with a single agent (80/114). After first progression to chemotherapy, treatment decisions were mainly driven by Performance Status and prior response to chemotherapy (>30 % patients). The most frequent all-settings second anticancer therapy regimen was vinflunine (70 % of single-agent and 42 % of all subsequent treatments), the main reasons evoked by physicians (>1 out of 4) being survival benefit, safety and phase III evidence. CONCLUSION: In this daily practice experience, a majority of patients with urothelial carcinoma previously treated with a platinum-based therapy received a second chemotherapy regimen, most often a single agent after an initial chemotherapy in the advanced setting and preferably a cytotoxic combination after a neoadjuvant or adjuvant chemotherapy. Performance Status and prior response to chemotherapy were the main drivers of further treatment decisions.

[Prostate cancer of elderly patients: Place and role of geriatric assessment]. / Cancer de prostate des sujets âgés : place et rôle de l'évaluation gériatrique.

INTRODUCTION: The aim of this study was to appreciate the place and role of geriatric assessment in elderly patients with prostate cancer. MATERIALS AND METHODS: We performed a retrospective analysis of prostate cancer patients who underwent geriatric assessment during the therapeutic management from 2008 to 2014. Patient, tumor, treatment characteristics and their associated toxicity as well as the parameters of geriatric assessment were studied. The occurrence of geriatric assessment within the 3 months preceding a therapeutic decision was reviewed. RESULTS: Data of seventy-four patients were analyzed with a median follow-up of 15.6 years. The average age at diagnosis was 74.3 and 80.6 at the geriatric assessment. At the time of the geriatric assessment 64 patients had metastatic disease, 39 were in poor condition more than 50% of patients had walking ability disorders. Thirteen patients underwent radical surgery, 28 received radiotherapy, 30 patients had chemotherapy and hormonotherapy was prescribed for 72 patients. The geriatric assessment, requested on average 15 years after diagnosis, was not carried out within the 3 months preceding treatment decision for 55 patients. CONCLUSION: The recourse to geriatric assessment is predominantly used to endorse a decision of supportive care for elderly patients with prostate cancer. An early intervention by a geriatrician consultant for the initial management and then at each therapeutic event is a sine qua non condition for efficient personalized therapeutic management suitable to every patient according to physiological age. LEVEL OF EVIDENCE: 4.

A multi-pronged approach to the search for an alternative to formaldehyde as an egg disinfectant without affecting worker health, hatching, or broiler production parameters.

Research was carried out to determine the effectiveness of 4 hatching eggs disinfection processes (i.e., disinfecting products and administration method) using a multi-pronged approach assessing the reduction of microbial eggshell contamination, the effects on worker exposure, hatching results and broiler performance, and, finally, suitability for use in commercial hatcheries. The 4 disinfection processes were: sodium dichlorocyanurate (DC) by thermonebulization, hydrogen peroxide 6% by nebulization (HP6), electrolyzed oxidizing water (EOW) by fogging, and hydrogen peroxide 30% vapor (HP30). In order to meet commercial hatchery conditions, the tested products were applied in an experimental hatchery by aerial disinfection in a dedicated room, not sprayed directly onto the eggs. Compared to the untreated control group, eggshell microbial load was significantly decreased by over 1 log10 cfu per egg in groups DC and HP30. These results were confirmed during a second experiment. In addition, these 2 products comply with legal requirements on worker exposure. Fertility and hatching results were significantly higher in group HP30 than in group DC, with no impact on chick quality and subsequent broiler performance. Under these study conditions, the disinfection process (i.e., administration of the product, contact with the eggs and aeration) lasted 65 min in group DC vs. 135 min in group HP30. When considering commercial hatchery conditions, this difference in application time confers a clear advantage on the DC process. Moreover, the investment required for HP30 is much higher than for DC. Overall, HP30 presented a clear advantage for hatching results whereas DC is a relatively more practical and less expensive disinfection process. To our knowledge, this is the first report on the use of hydrogen peroxide vapor as an egg disinfection process. Further research is needed to confirm the results of this study under commercial hatchery conditions.

Short-term effects of integrated motor imagery practice on muscle activation and force performance.

The effect of motor imagery (MI) practice on isometric force development is well-documented. However, whether practicing MI during rest periods of physical training improves the forthcoming performance remains unexplored. We involved 18 athletes in a counterbalanced design including three physical training sessions scheduled over five consecutive days. Training involved 10 maximal isometric contractions against a force plate, with the elbow at 90°. During two sessions, we integrated MI practice (focusing on either muscle activation or relaxation) during the inter-trial rest periods. We measured muscle performance from force plate and electromyograms of the biceps brachii and anterior deltoideus. We continuously monitored electrodermal activity (EDA) to control sympathetic nervous system activity. MI of muscle activation resulted in higher isometric force as compared to both MI of muscle relaxation and passive recovery (respectively +2.1% and +3.5%). MI practice of muscle relaxation also outperformed the control condition (+1.9%). Increased activation of the biceps brachii was recorded under both MI practice conditions compared to control. Biceps brachii activation was similar between the two MI practice conditions, but electromyography revealed a marginal trend toward greater activation of the anterior deltoideus during MI practice of muscle activation. EDA and self-reports indicated that these effects were independent from physiological arousal and motivation. These results might account for priming effects of MI practice yielding to higher muscle activation and force performance. Present findings may be of interest for applications in sports training and neurologic rehabilitation.

Neuroplasticity of prehensile neural networks after quadriplegia.

Targeting cortical neuroplasticity through rehabilitation-based practice is believed to enhance functional recovery after spinal cord injury (SCI). While prehensile performance is severely disturbed after C6-C7 SCI, subjects with tetraplegia can learn a compensatory passive prehension using the tenodesis effect. During tenodesis, an active wrist extension triggers a passive flexion of the fingers allowing grasping. We investigated whether motor imagery training could promote activity-dependent neuroplasticity and improve prehensile tenodesis performance. SCI participants (n=6) and healthy participants (HP, n=6) took part in a repeated measurement design. After an extended baseline period of 3 weeks including repeated magnetoencephalography (MEG) measurements, MI training was embedded within the classical course of physiotherapy for 5 additional weeks (three sessions per week). An immediate MEG post-test and a follow-up at 2 months were performed. Before MI training, compensatory activations and recruitment of deafferented cortical regions characterized the cortical activity during actual and imagined prehension in SCI participants. After MI training, MEG data yielded reduced compensatory activations. Cortical recruitment became similar to that in HP. Behavioral analysis evidenced decreased movement variability suggesting motor learning of tenodesis. Data suggest that MI training participated to reverse compensatory neuroplasticity in SCI participants, and promoted the integration of new upper limb prehensile coordination in the neural networks functionally dedicated to the control of healthy prehension before injury.

Autonomic nervous system correlates in movement observation and motor imagery.

The purpose of the current article is to provide a comprehensive overview of the literature offering a better understanding of the autonomic nervous system (ANS) correlates in motor imagery (MI) and movement observation. These are two high brain functions involving sensori-motor coupling, mediated by memory systems. How observing or mentally rehearsing a movement affect ANS activity has not been extensively investigated. The links between cognitive functions and ANS responses are not so obvious. We will first describe the organization of the ANS whose main purposes are controlling vital functions by maintaining the homeostasis of the organism and providing adaptive responses when changes occur either in the external or internal milieu. We will then review how scientific knowledge evolved, thus integrating recent findings related to ANS functioning, and show how these are linked to mental functions. In turn, we will describe how movement observation or MI may elicit physiological responses at the peripheral level of the autonomic effectors, thus eliciting autonomic correlates to cognitive activity. Key features of this paper are to draw a step-by step progression from the understanding of ANS physiology to its relationships with high mental processes such as movement observation or MI. We will further provide evidence that mental processes are co-programmed both at the somatic and autonomic levels of the central nervous system (CNS). We will thus detail how peripheral physiological responses may be analyzed to provide objective evidence that MI is actually performed. The main perspective is thus to consider that, during movement observation and MI, ANS activity is an objective witness of mental processes.

[Impact of quality improvement process upon the state of nutritional support in a critical care unit]. / Impacto de un proceso de mejora de la calidad en el estado del soporte nutricional en una unidad de cuidados intensivos.

INTRODUCTION: In a preceding article the state of Nutritional support (NS) in an Intensive Care Unit (ICU) was documented [Martinuzzi A et al. Estado del soporte nutricional en una unidad de Cuidados críticos. RNC 2011; 20: 5-17]. In this follow-up work we set to assess the impact of several organizational, recording and educational interventions upon the current state of NS processes. MATERIALS AND METHODS: Interventions comprised presentation of the results of the audit conducted at the ICU before the institution's medical as well as paramedical personnel; their publication in a periodical, peer-reviewed journal; drafting and implementation of a protocol regulating NS schemes to be carried out at the ICU; and conduction of continuous education activities on Nutrition (such as "experts talks", interactive courses, and training in the implementation of the NS protocol). The state of NS processes documented after the interventions was compared with the results annotated in the preceding article. Study observation window ran between March the 1st, 2011 and May 31th, 2011, both included. RESULTS: Study series differed only regarding overall-mortality: Phase 1: 40.0% vs. Phase 2: 20.5%; Difference: 19.5%; Z = 1.927; two-tailed-p = 0.054. Interventions resulted in a higher fulfillment rate of the prescribed NS indication; an increase in the number of patients receiving ≥ 80% of prescribed energy; and a reduction in the number of NS lost days. Mortality was (numerically) lower in patients in which the prescribed NS scheme was fulfilled, NS was early initiated, and whom received ≥ 80% of prescribed energy. Adopted interventions had no effect upon average energy intakes: Phase 1: 574.7 ± 395.3 kcal/24 h⁻¹ vs. Phase 2: 591.1 ± 315.3 kcal/24 h⁻¹; two-tailed-p > 0.05. CONCLUSIONS: Educational, recording and organizational interventions might result in a better conduction of NS processes, and thus, in a lower mortality. Hemodynamic instability is still the most formidable obstacle for initiating and completing NS.

Impacto de un proceso de mejora de la calidad en el estado del soporte nutricional en una unidad de cuidados intensivos / Impact of quality improvement process upon the state of nutritional support in a critical care unit

Introducción: En un artículo precedente se documentó el estado del Soporte nutricional (SN) en una Unidad de Terapia Intensiva (UTI) [Martinuzzi A y cols. Estado del soporte nutricional en una unidad de Cuidados críticos. RNC 2011; 20: 5-17]. En este trabajo de seguimiento nos propusimos evaluar el impacto de varias intervenciones educativas, registrales y organizativas hechas en la Unidad sobre el estado actual de los procesos del SN. Material y método: Las intervenciones incluyeron la presentación de los resultados de la auditoría hecha en la UTI ante el plantel médico y paramédico de la institución; la publicación de los mismos en una revista periódica, arbitrada por pares; la redacción e implementación de un protocolo normativo de los esquemas de SN a conducir en la UTI; y la celebración de actividades de educación continuada en Nutrición (como "charlas con expertos", cursos interactivos, y capacitación en la implementación del protocolo de SN). El estado de los procesos de SN documentado tras las intervenciones se comparó con los resultados anotados en el trabajo precedente. La ventana de observación del estudio se extendió entre el 1 de Marzo del 2011 y el 31 mayo del 2011, ambos incluidos. Resultados: Las series de estudio difirieron entre sí solo respecto de la mortalidad: Fase 1: 40.0% vs. Fase 2: 20,5%; Diferencia: 19,5%; Z = 1,927; p-de-2-colas = 0,054. Las intervenciones hechas resultaron en una mayor tasa de cumplimiento de la indicación prescrita de SN; un aumento en el número de enfermos que recibieron > 80% de la energía prescrita; y una reducción en el número de días de SN perdidos. La mortalidad fue (numéricamente) menor en los pacientes en los que se cumplió el esquema prescrito de SN, el SN se inició tempranamente, y que recibieron > 80% de la energía prescrita. Las intervenciones adoptadas no tuvieron efecto sobre los aportes promedio de energía: Fase 1: 574,7 ± 395,3 kcal/24 h-1 vs. Fase 2: 591,1 ± 315,3 kcal/24 h-1; p > 0,05. Conclusiones: Las intervenciones educativas, registrales y organizativas pueden resultar en una mejor conducción de los procesos de SN, y con ello, en una menor mortalidad. La inestabilidad hemodinámica sigue siendo el obstáculo más formidable en el inicio y mantenimiento del SN (AU)

Introduction: In a preceding article the state of Nutritional support (NS) in an Intensive Care Unit (ICU) was documented [Martinuzzi A et al. Estado del soporte nutricional en una unidad de Cuidados críticos. RNC 2011; 20: 5-17]. In this follow-up work we set to assess the impact of several organizational, recording and educational interventions upon the current state of NS processes. Materials and methods: Interventions comprised presentation of the results of the audit conducted at the ICU before the institution's medical as well as paramedical personnel; their publication in a periodical, peerreviewed journal; drafting and implementation of a protocol regulating NS schemes to be carried out at the ICU; and conduction of continuous education activities on Nutrition (such as "experts talks", interactive courses, and training in the implementation of the NS protocol). The state of NS processes documented after the interventions was compared with the results annotated in the preceding article. Study observation window ran between March the 1st, 2011 and May 31th, 2011, both included. Results: Study series differed only regarding overallmortality: Phase 1: 40.0% vs. Phase 2: 20.5%; Difference: 19.5%; Z = 1.927; two-tailed-p = 0.054. Interventions resulted in a higher fulfillment rate of the prescribed NS indication; an increase in the number of patients receiving > 80% of prescribed energy; and a reduction in the number of NS lost days. Mortality was (numerically) lower in patients in which the prescribed NS scheme was fulfilled, NS was early initiated, and whom received > 80% of prescribed energy. Adopted interventions had no effect upon average energy intakes: Phase 1: 574.7 ± 395.3 kcal/24 h-1 vs. Phase 2: 591.1 ± 315.3 kcal/24 h1; two-tailed-p > 0.05. Conclusions: Educational, recording and organizational interventions might result in a better conduction of NS processes, and thus, in a lower mortality. Hemodynamic instability is still the most formidable obstacle for initiating and completing NS (AU)

Could motor imagery be effective in upper limb rehabilitation of individuals with spinal cord injury? A case study.

STUDY DESIGN: A case study. OBJECTIVE: The aim was to investigate whether motor imagery (MI) could be successfully incorporated into conventional therapy among individuals with spinal cord injury (SCI) to improve upper limb (UL) function. SETTING: The Physical Medicine and Rehabilitation Unit at the Henry Gabrielle Hospital in Lyon, France. METHODS: The participant was an individual with a complete C6 SCI. MI content was focused on functional UL movements, to improve hand transport to reach out and grasp with tenodesis. The participant was tested before and after 15 MI training sessions (45 min each, three times a week during 5 consecutive weeks). MI ability and program compliance were used as indicators of feasibility. The Minnesota and Box and Blocks tests, as well as movement time and hand trajectory during targeted movements were the dependent variables, evaluating motor performance before and after MI training. RESULTS: The participant's ability to generate MI was checked and compliance with the rehabilitation program was confirmed. The time needed to complete the Minnesota test decreased by 1 min 25 s. The Box and Blocks score was improved by three units after MI program. Decreased movement time and enhanced hand trajectory smoothness were still observed 3 months later, despite a slight decrease in performance. CONCLUSIONS: This study supports the feasibility for introducing MI in conventional therapy. Further studies should confirm the potential role of MI in motor recovery with a larger sample.

Rgg proteins associated with internalized small hydrophobic peptides: a new quorum-sensing mechanism in streptococci.

We identified a genetic context encoding a transcriptional regulator of the Rgg family and a small hydrophobic peptide (SHP) in nearly all streptococci and suggested that it may be involved in a new quorum-sensing mechanism, with SHP playing the role of a pheromone. Here, we provide further support for this hypothesis by constructing a phylogenetic tree of the Rgg and Rgg-like proteins from Gram-positive bacteria and by studying the shp/rgg1358 locus of Streptococcus thermophilus LMD-9. We identified the shp1358 gene as a target of Rgg1358, and used it to confirm the existence of the steps of a quorum-sensing mechanism including secretion, maturation and reimportation of the pheromone into the cell. We used surface plasmon resonance to demonstrate interaction between the pheromone and the regulatory protein and performed electrophoretic mobility shift assays to assess binding of the transcriptional regulator to the promoter regions of its target genes. The active form of the pheromone was identified by mass spectrometry. Our findings demonstrate that the shp/rgg1358 locus encodes two components of a novel quorum-sensing mechanism involving a transcriptional regulator of the Rgg family and a SHP pheromone that is detected and reimported into the cell by the Ami oligopeptide transporter.

Postural control during visual and kinesthetic motor imagery.

Despite the accumulating evidence supporting an interaction between cognitive functions and postural control, little is known about the selective impact of the mental representation of an action, i.e., motor imagery (MI) on postural control. As postural oscillations are reduced during a cognitive task of backward silent counting, a greater stability is also expected during MI compared to a no-task condition (standing). Twenty participants took part in this experiment, which aimed at providing evidence that MI may improve postural stability. They were requested to mentally imagine a movement while standing on a force-plate. Results showed a decrease in both path length and postural sway variability on the anterior-posterior and lateral axes during all dual-task sessions, as compared to the motionless condition. These postural adjustments might result from both central and peripheral processes, and/or increased muscle stiffness. Conversely, postural oscillation amplitude increased on the vertical axis during MI of three vertical jumps, hence suggesting that postural regulations remain task-related during MI. Finally, our data showed that kinesthetic and visual imagery differentially impacted the postural regulation.

Phoning while driving I: a review of epidemiological, psychological, behavioural and physiological studies.

The impact of cell (mobile) phone use on driving performance has been widely questioned for 20 years. This paper reviews the literature to evaluate the extent to which phoning may impact behaviour with a risk to affect safety. After analysing epidemiological studies that give an overview of cell phone use, this paper examines the experimental results and focuses on variables showing that driving is impacted by holding a mobile-phone conversation. Information processing (e.g. reaction time and detection rate of cues related to driving information) and variables associated with vehicle control (e.g. lane-keeping, headway and vehicle speed) seem the most relevant. Although less studied than behavioural indices, physiological data give information about the supplementary potential strain that the driver may undergo under dual-task conditions. This first part of the review highlights common findings, questionable results and differences among studies, which originate from specific experimental designs with particular dependent variables, i.e. self-report, behavioural and physiological indicators. Finally, how drivers try to compensate for the additional load brought by phone use is described. STATEMENT OF RELEVANCE: The two papers review the influence of mobile-phone use on driving performance. While there is ample evidence that this dual task is likely to increase the risk of car crash, the review analyses the variables eliciting detrimental conditions and, conversely, those that may preserve acceptable conditions for safety, close to usual driving. The decision of answering or initiating a cell phone call while driving depends upon the complex interaction among several variables, including driving conditions and driver's own characteristics. In addition, this decision remains under driver's awareness of being able or not to manage the two tasks simultaneously.

Phoning while driving II: a review of driving conditions influence.

The first paper examined how the variables related to driving performance were impacted by the management of holding a phone conversation. However, the conditions under which this dual task is carried out are dependent upon a set of factors that may particularly influence the risk of crash. These conditions are defined by several independent variables, classified into five main categories: i) legislation; ii) phone type (hands-free or hand-held); iii) drivers' features regarding age, gender, personal individual profile and driving experience; iv) conversation content (casual or professional) and its context (held with passengers or with a cell (mobile) phone); v) driving conditions (actual or simulated driving, road type, traffic density and weather). These independent variables determine the general conditions. The way in which these factors are combined and interact one with another thus determines the risk that drivers undergo when a cell phone is used while driving. Finally, this review defined the general conditions of driving for which managing a phone conversation is likely to elicit a high risk of car crash or, conversely, may provide a situation of lower risk, with sufficient acceptance to ensure safety.

Targeted agents in metastatic Xp11 translocation/TFE3 gene fusion renal cell carcinoma (RCC): a report from the Juvenile RCC Network.

BACKGROUND: Xp11 translocation renal cell carcinoma (RCC) is an RCC subtype affecting 15% of RCC patients <45 years. We analyzed the benefit of targeted therapy [vascular endothelial growth factor receptor (VEGFR)-targeted agents and/or mammalian target of rapamycin (mTOR) inhibitors] in these patients. PATIENTS AND METHODS: Patients with Xp11 translocation/TFE3 fusion gene metastatic RCC who had received targeted therapy were identified. Nuclear TFE3 positivity was confirmed by reviewing pathology slides. Responses according to RECIST criteria, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: Overall, 53 patients were identified; 23 had metastatic disease, and of these 21 had received targeted therapy (median age 34 years). Seven patients achieved an objective response. In first line, median PFS was 8.2 months [95% confidence interval (CI) 2.6-14.7 months] for sunitinib (n = 11) versus 2 months (95% CI 0.8-3.3 months) for cytokines (n = 9) (log-rank P = 0.003). Results for further treatment (second, third, or fourth line) were as follows: all three patients receiving sunitinib had a partial response (median PFS 11 months). Seven of eight patients receiving sorafenib had stable disease (median PFS 6 months). One patient receiving mTOR inhibitors had a partial response and six patients had stable disease. Median OS was 27 months with a 19 months median follow-up. CONCLUSION: In Xp11 translocation RCC, targeted therapy achieved objective responses and prolonged PFS similar to those reported for clear-cell RCC.