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Background: Placebo use is widespread in clinical practice. However, they are most often administered deceptively rather than openly. It is often suggested that open‐label placebos (OLP) are less effective than deceptive placebos (DP). This study aimed to compare the use of DP and OLP treatments to reduce pain in healthy volunteers. Methods: We conducted a non‐inferiority, parallel, randomized, controlled trial, which also included a nested cross‐over no‐treatment condition. This study was conducted at a university clinic in France. Results: We included 60 subjects and the main result shows that the OLP was not inferior to the DP by a margin of 10 mm. The mean difference between both groups regarding intensity of pain was 0.7 mm with a 95% compatibility interval (95% CI) of ]−∞; 5.4], and 97.5% CI of ]−∞; 6.3]. Secondary outcomes require cautious interpretation of the effect of placebo versus no treatment due to a time–treatment interaction. Conclusion: The study indicates that OLP may perform just as well as DP and could provide support for the use of OLP as an ethical alternative to DP when they are to be used in a clinical setting. If only patients knew about the placebo nature of some treatments they are receiving, unnecessary lies could be avoided while maintaining similar placebo effects. Significance: This study is the first to show non‐inferiority of placebos administered honestly, also called OLP, compared to DP in reducing pain. This suggests that OLP could be as effective as their deceptive counterparts while having the ethical advantage of not being required to lie. If deception is not a necessary condition for efficacy, OLP should be preferred over DP. [ABSTRACT FROM AUTHOR]

Background: A new model of care enables French physiotherapists (PT) working in collaboration with family physicians (FP) to expand their usual scope of practice for patients with acute low back pain (LBP). The aim of our study is to evaluate the impact of this new first-contact physiotherapy (FCP) advanced practice model compared to usual FP care., Methods: A multicentre pragmatic non-inferiority cluster randomised controlled trial (RCT) has been conducted in six multidisciplinary primary healthcare centres in France. Patients from 20 to 55 years old with acute LBP consulted either the PT or the FP. PT independently assessed and managed patients including medication prescription. The primary outcome measure was disability at six weeks (Roland Morris Disability Questionnaire, range 0-24). Secondary outcomes include pain, risk disability prognosis, satisfaction with care, healthcare resources use and wait times. Data were collected at baseline, six and twelve weeks. Outcomes across arms were compared using mixed models regression analysis. Except for non-inferiority analysis of the primary outcome measure, other analyses were performed with a two-sided significance level of 0.05., Results: Sixty patients were recruited (PT: 32, FP: 28). The adjusted mean difference between groups for disability at 6 weeks was 0.39 in favour of the FP group (95%CI: -2.03; 2.81, p = 0.753). Considering a 5 points minimal clinically important difference, the FCP-led model of care was not inferior to usual FP care for the primary outcome. There was no statistically significant difference between groups in disability at 3 months and pain at 6 weeks and 3 months. PTs prescribed significantly less medications than FPs (p < 0.001). No statistically significant difference was found for other healthcare resource use outcomes, patients' satisfaction and wait times., Conclusion: This is the first RCT to evaluate the impact of a FCP advanced practice model of care including medical delegated acts in a primary care setting. Our results suggest that the FCP-led model of care is not inferior to usual FP care regarding disability at 6 weeks. The FCP model could result in possible benefits in terms of healthcare resources use. Further adequate powered studies with larger sample size are needed to draw stronger conclusions., Trial Registration: The study has been registered in ClinicalTrials.gov (NCT05200533) on the 20th of January 2022., Competing Interests: Declarations Ethics approval and consent to participate The study have been conducted in accordance with the Declaration of Helsinki. Ethical approval was obtained from the French ethics committee: Comité de Protection des Personnes Ouest IV Nantes (Committee for the protection of subjects West Nantes IV, number 21.01537.000012). All participants offered written informed consent prior to the enrolment in the study. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The current use of TiO 2 nanoparticles raises questions about their impact on our health. Cells interact with these nanoparticles via the phospholipid membrane and, in particular, the phosphate head. This highlights the significance of understanding the interaction between phosphates and nanoparticles possessing distinct crystalline structures, specifically anatase and rutile. It is crucial to determine whether this adsorption varies based on the exposed facet(s). Consequently, various nanoparticles of anatase and rutile TiO 2 , characterized by well-defined morphologies, were synthesized. In the case of the anatase samples, bipyramids, needles, and cubes were obtained. For the rutile samples, all exhibited a needle-like shape, featuring {110} facets along the long direction of the needles and facets {111} on the upper and lower parts. Phosphate adsorption experiments carried out at pH 2 revealed that the maximum adsorption was relatively consistent across all samples, averaging around 1.5 phosphate·nm -2 in all cases. Experiments using infrared spectroscopy on dried TiO 2 powders showed that phosphates were chemisorbed on the surfaces and that the mode of adsorption depended on the crystalline phase and the nature of the facet: the anatase phase favors bidentate adsorption more than the rutile crystalline phase.

Tricalcium phosphate (TCP) is a food additive, labeled E341(iii), used in powdered food preparation, such as baby formula. In the United States, calcium phosphate nano-objects were identified in baby formula extractions. Our goal is to determine whether the TCP food additive, as is used in Europe, can be classified as a nanomaterial. The physicochemical properties of TCP were characterized. Three different samples (from a chemical company and two manufacturers) were thoroughly characterized according to the recommendations of the European Food Safety Authority. A commercial TCP food additive was identified as actually being hydroxyapatite (HA). It presents itself in the form of particles of different shapes (either needle-like, rod, or pseudo-spherical), which were demonstrated in this paper to be of a nanometric dimension: E341(iii) is thus a nanomaterial. In water, HA particles sediment rapidly as agglomerates or aggregates over a pH of 6 and are progressively dissolved in acidic media (pH < 5) until the complete dissolution at a pH of 2. Consequently, since TCP may be considered as a nanomaterial on the European market, it raises the question of its potential persistency in the gastrointestinal tract.

Background: To date, the use of the plethysmographic variability index (PVI) has not been recommended to guide fluid management in the paediatric surgical population. This systematic review and meta-analysis aimed to summarise available evidence about the diagnostic accuracy of digital PVI to predict fluid responsiveness in mechanically ventilated children., Methods: We searched the Pubmed, Embase and Web of Science databases, from inception to January 2022, to identify all relevant studies that investigated the ability of the PVI recorded at the finger to predict fluid responsiveness in mechanically ventilated children. Using a random-effects model, we calculated pooled values of diagnostic odds ratio, sensitivity, and specificity of PVI to predict the response to fluid challenge., Results: Eight studies met the inclusion criteria with a total of 283 patients and 360 fluid challenges. All the studies were carried out in a surgical setting. The area under the summary receiver operating characteristic curve of PVI to predict fluid responsiveness was 0.82. The pooled sensitivity, specificity, and diagnostic odds ratio of PVI for the overall population were 72.4% [95% CI: 65.3-78.7], 65.9% [58.5-72.8], and 9.26 [5.31-16.16], respectively., Conclusion: Our results suggest that digital PVI is a reliable predictor for fluid responsiveness in mechanically ventilated children in the perioperative setting. The diagnostic performance of digital PVI reported in our work for discrimination between responders and non-responders to the fluid challenge was however not as high as previously reported in the adult population., (Copyright © 2023 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Background: Diet is one of the most important modifiable lifestyle factors in human health and in chronic disease prevention. Thus, accurate dietary assessment is essential for reliably evaluating adherence to healthy habits., Objectives: The aim of this study was to identify urinary metabolites that could serve as robust biomarkers of diet quality, as assessed through the Alternative Healthy Eating Index (AHEI-2010)., Design: We set up two-center samples of 160 healthy volunteers, aged between 25 and 50, living as a couple or family, with repeated urine sampling and dietary assessment at baseline, and 6 and 12 months over a year. Urine samples were subjected to large-scale metabolomics analysis for comprehensive quantitative characterization of the food-related metabolome. Then, lasso regularized regression analysis and limma univariate analysis were applied to identify those metabolites associated with the AHEI-2010, and to investigate the reproducibility of these associations over time., Results: Several polyphenol microbial metabolites were found to be positively associated with the AHEI-2010 score; urinary enterolactone glucuronide showed a reproducible association at the three study time points [false discovery rate (FDR): 0.016, 0.014, 0.016]. Furthermore, other associations were found between the AHEI-2010 and various metabolites related to the intake of coffee, red meat and fish, whereas other polyphenol phase II metabolites were associated with higher AHEI-2010 scores at one of the three time points investigated (FDR < 0.05 or β ≠ 0)., Conclusion: We have demonstrated that urinary metabolites, and particularly microbiota-derived metabolites, could serve as reliable indicators of adherence to healthy dietary habits., Clinical Trail Registration: www.ClinicalTrials.gov, Identifier: NCT03169088., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Castellano-Escuder, González-Domínguez, Vaillant, Casas-Agustench, Hidalgo-Liberona, Estanyol-Torres, Wilson, Beckmann, Lloyd, Oberli, Moinard, Pison, Borel, Joyeux-Faure, Sicard, Artemova, Terrisse, Dancer, Draper, Sánchez-Pla and Andres-Lacueva.)

Background: Tension in the supply of highly consumed drugs for patients with COVID-19 (propofol, midazolam, curares) led the French government to set up a centralized supply of hospitals with distribution based on the number of resuscitation beds in March 2020. The French Societies of Clinical Pharmacy and of Anesthesia and Critical Care aimed to evaluate the changes in total needs and the distribution between anesthesia and critical care activities (CCU), to prepare resumed surgical activity., Methods: National declarative survey among pharmacists, via an online form (SurveyMonkey®), was conducted in April and May 2020. The analysis focused on quantities dispensed during the whole year 2019, and March and April of year 2019 and 2020 for the drugs subject to quota, and on their distribution in CCU and operating theaters., Results: For the 358 establishments (47% public, 53% private), dispensations in CCU in March 2020 compared to March 2019 increased, respectively: propofol (+81%), midazolam (+125%), cisatracurium (+311%), atracurium (+138%), rocuronium (+119%); and decreased for anaesthesia: propofol (-27%), midazolam (-10%), cisatracurium (-19%), atracurium (-27%), rocuronium (+16%)., Conclusions: Variation of dispensations between CCU and others was directly related to the increase of COVID patients in CCU and the decrease in surgical activity. Each establishment could receive up to five or six different presentations and concentrations, leading to a major risk of medication error. This collaborative national survey provided accurate data on the drugs' usual consumption. This work emphasized the need for a strong collaboration between pharmacists and anesthesiologists and intensive care physicians. It was further used by the Health Ministry to adjust the drug distribution., (© 2022. The Author(s).)

Background: A multimodal strategy to prevent nosocomial influenza was implemented in 2015-2016 in Grenoble Alpes University Hospital. Three modalities were implemented in all units: promotion of vaccination among healthcare workers, epidemiologic surveillance and communication campaigns. Units receiving a high number of patients with influenza implemented 2 additional modalities: improvement of diagnosis capacities and systematic surgical mask use. The main objective was to assess the effectiveness of the strategy for reducing the risk of nosocomial influenza., Methods: A study was conducted retrospectively investigating 5 epidemic seasons (2014-2015 to 2018-2019) including all patients hospitalized with a positive influenza test at Grenoble Alpes University Hospital. The weekly number of nosocomial influenza cases was analyzed by Poisson regression and incidence rate ratios (IRR) were estimated., Results: A total of 1540 patients, resulting in 1559 stays, were included. There was no significant difference between the 5 influenza epidemic seasons in the units implementing only 3 measures. In the units implementing the 5 measures, there was a reduction of nosocomial influenza over the seasons when the strategy was implemented compared to the 2014-2015 epidemic season (IRR = 0.56, 95% CI = 0.23-1.34 in 2015-2016; IRR = 0.39, 95% CI = 0.19-0.81 in 2016-2017; IRR = 0.50, 95% CI = 0.24-1.03 in 2017-2018; IRR = 0.48, 95% CI = 0.23-0.97 in 2018-2019)., Conclusions: Our data mainly suggested that the application of the strategy with 5 modalities, including systematic surgical mask use and rapid diagnosis, seemed to reduce by half the risk of nosocomial influenza. Further data, including medico-economic studies, are necessary to determine the opportunity of extending these measures at a larger scale., (© 2022. The Author(s).)

The benefits of physical activity during cancer care and rehabilitation are well established, however introducing and maintaining healthy behaviors in the long-term remains challenging. Technological advances in electrically assisted bicycles and on-board sensors led us to propose an original rehabilitation program combining smart electric bicycle outings with health education. This was a pilot study with physical activity questionnaires and endurance tests to evaluate physical activity following a 6-week program comprising 2 bicycle outings per week in groups of 5 (supervised or not) with briefing and debriefing supplemented by health education sessions. Fourteen post-breast cancer patients participated (median age 52 [IQR 46-55]). A gain of at least 2 International Physical Activity Questionnaire points and over 600 MET.min/week was achieved by 9/10 (90%; 95%CI[55.5-99.7]) women. The feasibility of the program was clearly demonstrated, with excellent patient adherence (11/12 planned 2 h outings per patient). The electric bicycle program strengthened the womens' physiological capacities through personalized levels of electrical assistance made possible by the fine settings of the motorization. This enabled the whole group to achieve the outing objectives together despite very variable levels of deconditioning. The pleasure shared in the group activity and personal empowerment gained should promote long-term maintenance of physical activity., (Copyright © 2022 IPEM. Published by Elsevier Ltd. All rights reserved.)

Titanium dioxide is a food additive that has raised some concerns for humans due to the presence of nanoparticles. We were interested in knowing the fate of TiO2 particles in the gastro-intestinal tract and their potential effect on digestive enzymes. For this purpose, we analysed the behaviour of two different food grade TiO2 samples (E171) and one nano-sized TiO2 sample (P25) through a standardized static in vitro digestion protocol simulating the oral, gastric and intestinal phases with appropriate juices including enzymes. Both E171 and P25 TiO2 particles remained intact in the digestive fluids but formed large agglomerates, and especially in the intestinal fluid where up to 500 μm sized particles have been identified. The formation of these agglomerates is mediated by the adsorption of mainly α-amylase and divalent cations. Pepsin was also identified to adsorb onto TiO2 particles but only in the case of silica-covered E171. In the salivary conditions, TiO2 exerted an inhibitory action on the enzymatic activity of α-amylase. The activity was reduced by a factor dependent on enzyme concentrations (up to 34% at 1 mg mL-1) but this inhibitory effect was reduced to hardly 10% in the intestinal fluid. In the gastric phase, pepsin was not affected by any form of TiO2. Our results hint that food grade TiO2 has a limited impact on the global digestion of carbohydrates and proteins. However, the reduced activity specifically observed in the oral phase deserves deeper investigation to prevent any adverse health effects related to the slowdown of carbohydrate metabolism.

Background: Despite thorough and validated clinical guidelines based on bipolar disorders subtypes, large pharmacological treatment heterogeneity remains in these patients. There is limited knowledge about the different treatment combinations used and their influence on patient outcomes. We attempted to determine profiles of patients based on their treatments and to understand the clinical characteristics associated with these treatment profiles., Methods: This multicentre longitudinal study was performed on a French nationwide bipolar cohort database. We performed hierarchical agglomerative clustering to search for clusters of individuals based on their treatments during the first year following inclusion. We then compared patient clinical characteristics according to these clusters., Results: Four groups were identified among the 1795 included patients: group 1 ("heterogeneous" n = 1099), group 2 ("lithium" n = 265), group 3 ("valproate" n = 268), and group 4 ("lamotrigine" n = 163). Proportion of bipolar 1 disorder, in groups 1 to 4 were: 48.2%, 57.0%, 48.9% and 32.5%. Groups 1 and 4 had greater functional impact at baseline and a less favorable clinical and functioning evolution at one-year follow-up, especially on GAF and FAST scales., Limitations: The one-year period used for the analysis of mood stabilizing treatments remains short in the evolution of bipolar disorder., Conclusions: Treatment profiles are associated with functional evolution of patients and were not clearly determined by bipolar subtypes. These profiles seem to group together common patient phenotypes. These findings do not seem to be influenced by the duration of disease prior to inclusion and neither by the number of treatments used during the follow-up period., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Positive communication behaviour within anaesthesia teams may decrease stress response and improve clinical performance. We aimed to evaluate the effect of positive communication during medical handover on the subsequent team-based clinical performance in a simulated critical situation. We also assessed the effect of positive communication behaviour on stress response., Methods: This single-centre RCT involved anaesthesia teams composed of a resident and a nurse in a high-fidelity scenario of anaesthesia-related paediatric laryngospasm after a standardised handover. During the handover, similar information was provided to all teams, but positive communication behaviour was adopted only for teams in the intervention group. Primary outcome was team-based clinical performance, assessed by an independent blinded observer, using video recordings and a 0-to 100-point scenario-specific scoring tool. Three categories of tasks were considered: safety checks before the incision, diagnosis/treatment of laryngospasm, and crisis resource management/non-technical skills. Individual stress response was monitored by perceived level of stress and HR variability., Results: The clinical performance of 64 anaesthesia professionals (grouped into 32 teams) was analysed. The mean (standard deviation) team-based performance score in the intervention group was 44 (10) points vs 35 (12) in the control group (difference: +8.4; CI 95% [0.4-16.4]; P=0.04). The effects were homogeneous over the three categories of tasks. Perceived level of stress and HR variability were not significantly different between groups., Conclusions: Positive communication behaviour between healthcare professionals during medical handover improved team-based performance in a simulation-based critical situation., Clinical Trial Registration: NCT03375073., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

In the current study, we provide the list of pharmacological interventions applied during the one-year follow-up period of the Pharmacological treatment profiles in the FACE-BD cohort study. These data show the treatments used in the new clusters formed in this previous study and also in usual bipolarity subtypes. The proportion of each treatment used during the follow-up was calculated. Days on each treatment were also included in this dataset. The complete clinical and paraclinical data analyzed for clusters and bipolar subtypes were included in this dataset. Socio-demographic self-administered and clinician-administered scales, clinical evaluation during the follow-up, psychiatric and somatic comorbidities, and blood tests are shown in this material., Competing Interests: Dr. Brodeur, H. Terrisse, Dr. Pouchon, O. Godin, Dr. Aubin, Dr. Bellivier, Dr. Belzeaux, Dr. Bougerol, Dr. Courtet, Dr. Dubertret, Dr. Gard, Dr. Henry, Dr. Leboyer, Dr. Roux, Dr. Schwan, Dr. Bosson have nothing to disclose. Dr. Aouizerate reports personal fees from Janssen-Cilag, personal fees from Lilly, personal fees from Sanofi, during the conduct of the study. Dr. Haffen reports personal fees and non-financial support from Janssen, personal fees and non-financial support from Lundbeck, personal fees and non-financial support from Otsuka, outside the submitted work. Dr. Olié reports personal fees from Janssen-Cilag, outside the submitted work. Dr. Samalin reports personal fees and non-financial support from Janssen, personal fees and non-financial support from Lundbeck, personal fees and non-financial support from Otsuka, outside the submitted work. Dr. Etain reports grants from INSERM, grants from Assistance Publique des Hôpitaux de Paris, grants from Agence Nationale pour la Recherche, grants from Fondation de France, grants from Research Council of Norway, personal fees from SANOFI, outside the submitted work. Dr. Polosan reports personal fees from Lundbeck, personal fees from Janssen-Cilag, outside the submitted work. The FondaMental Advanced Centers of Expertise in Bipolar Disorders (FACE-BD) Collaborators have no conflicts of interest to disclose except PM Llorca. PM Llorca has received grants, honoraria, or consulting fees from ESAI, Gedeon Richeter, Janssen, Lundbeck, Otsuka and Sanofi., (© 2021 The Authors.)

Colloidal silver products are sold for a wide range of disinfectant and health applications. This has increased the potential for human exposure to silver nanoparticles (AgNPs) and ions (Ag + ), for which oral ingestion is considered to be a major route of exposure. Our objective was to evaluate and compare the toxicity of two commercially available colloidal silver products on two human intestinal epithelial models under realistic exposure conditions. Mesosilver™ and AgC were characterized and a concentration range between 0.1 and 12 μg/mL chosen. Caco-2 cells vs. co-culture of Caco-2 and mucus-secreting HT29-MTX cells (90/10) were used. Repeated exposure was carried out to determine cell viability over 18 days of cell differentiation in 24-well plates. Selected concentrations (0.1, 1, and 3 μg/mL) were tested on cells cultured in E-plates and Transwells with the same repeated exposure regimen, to determine cell impedance, and cell viability and trans-epithelial electrical resistance (TEER), respectively. Silver uptake, intracellular localisation, and translocation were determined by CytoViva™, HIM-SIMS, and ICP-MS. Genotoxicity was determined on acutely-exposed proliferating Caco-2 cells by γH2AX immunofluorescence staining. Repeated exposure of a given concentration of AgC, which is composed solely of ionic silver, generally exerted more toxic effects on Caco-2 cells than Mesosilver™, which contains a mix of AgNPs and ionic silver. Due to its patchy structure, the presence of mucus in the Caco-2/HT29-MTX co-culture only slightly mitigated the deleterious effects on cell viability. Increased genotoxicity was observed for AgC on proliferating Caco-2 cells. Silver uptake, intracellular localisation, and translocation were similar. In conclusion, Mesosilver™ and AgC colloidal silver products show different levels of gut toxicity due to the forms of distinct silver (AgNPs and/or Ag + ) contained within. This study highlights the applicability of high-resolution (chemical) imaging to detect and localize silver and provides insights into its uptake mechanisms, intracellular fate and cellular effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Some surgical site infections (SSI) could be prevented by following adequate infection prevention and control (IPC) measures. Poor compliance with IPC measures often occurs due to knowledge gaps and insufficient education of healthcare professionals. The education and training of SSI preventive measures does not usually take place in the operating room (OR), due to safety, and organisational and logistic issues. The proposed study aims to compare virtual reality (VR) as a tool for medical students to learn the SSI prevention measures and adequate behaviours (eg, limit movements…) in the OR, to conventional teaching., Methods and Analysis: This protocol describes a randomised controlled multicentre trial comparing an educational intervention based on VR simulation to routine education. This multicentre study will be performed in three universities: Grenoble Alpes University (France), Imperial College London (UK) and University of Heidelberg (Germany). Third-year medical students of each university will be randomised in two groups. The students randomised in the intervention group will follow VR teaching. The students randomised in the control group will follow a conventional education programme. Primary outcome will be the difference between scores obtained at the IPC exam at the end of the year between the two groups. The written exam will be the same in the three countries. Secondary outcomes will be satisfaction and students' progression for the VR group. The data will be analysed with intention-to-treat and per protocol., Ethics and Dissemination: This study has been approved by the Medical Education Ethics Committee of the London Imperial College (MEEC1920-172), by the Ethical Committee for the Research of Grenoble Alpes University (CER Grenoble Alpes-Avis-2019-099-24-2) and by the Ethics Committee of the Medical Faculty of Heidelberg University (S-765/2019). Results will be published in peer-reviewed medical journals, communicated to participants, general public and all relevant stakeholders., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Placebo has been studied for many years and is ever-present in healthcare. In clinical practice, its use is limited by ethical issues raised by the deception entailed by its administration. Objective: To investigate whether, when given detailed information about pain and underlying placebo mechanisms, subjects will have a response similar to that of those subjected to a procedure in which they receive a conventional placebo treatment. Methods: The study is designed as a non-inferiority randomized, parallel with a nested crossover trial. In addition, 126 subjects without any known pathology will be included. They will be randomized into two groups. Each subject will undergo three Cold Pressor Tests (CPT): calibration, condition of interest (deceptive placebo or educated placebo), and control. Our main judgment criterion will be the comparison in pain intensity experienced on the visual analog scale between the two CPTs with placebo conditions. Results: This study will allow us to rule on the non-inferiority of an "educated" placebo compared to a deceptive placebo in the context of an acute painful stimulation. It is another step towards the understanding of open-label placebo and its use in clinical practice. Conclusions: This study has been approved by the ethics committee in France (2017-A01643-50) and registered on ClinicalTrials.gov (NCT03934138).

Background: Cancer patients who develop a deep-vein thrombosis (DVT) or a pulmonary embolism (PE) are at higher risk of death than similar cancer patients who do not develop DVT or PE. The impact of isolated superficial venous thrombosis (SVT) (i.e. without DVT or PE) on the prognosis of cancer patients is unknown., Methods: Data from the OPTIMEV, multicentre, observational study, to compare at 3 years the incidences of death, DVT-PE recurrence and bleeding of cancer patients with objectively confirmed SVT vs. cancer patients with DVT (matched 1:2 on age, sex, cancer stage) and vs. patients with SVT without cancer (matched 1:3 on age and sex)., Results: Cancer patients with SVT (n = 34) had a high risk of death (23.2%patient-year(PY)), that was similar to that of cancer patients with DVT (aHR = 1.0[0.6-1.9]) and higher to that of SVT patients without cancer (aHR = 9.0[3.5-23.1]). Cancer patients with SVT received anticoagulants for a median duration of 45 days and had a high risk of DVT-PE recurrence (6.0%PY), similar to that of cancer patients with DVT (adjusted cause-specific HR (aCHR) = 1.5[0.4-5.8]) and higher to that of SVT patients without cancer (aCHR = 2.9[0.7-11.9]). In our population, venous thrombosis on varicose veins was associated with a lower risk of death (aHR = 0.6[0.3-1.0]) and DVT-PE recurrence (aCHR = 0.6[0.2-1.7])., Conclusion: Our results suggest that cancer patients with SVT have a poor prognosis, similar to that of patients with cancer-related DVT. The high rate of DVT-PE recurrence suggests that such patients may need longer duration of anticoagulant treatment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Titanium dioxide is a metal oxide used as a white pigment in many food categories, including confectionery. Due to differences in the mass fraction of nanoparticles contained in TiO 2 , the estimated intakes of TiO 2 nanoparticles differ by a factor of 10 in the literature. To resolve this problem, a better estimation of the mass of nanoparticles present in food products is needed. In this study, we focused our efforts on chewing gum, which is one of the food products contributing most to the intake of TiO 2 . The coatings of four kinds of chewing gum, where the presence of TiO 2 was confirmed by Raman spectroscopy, were extracted in aqueous phases. The extracts were analysed by transmission electron microscopy (TEM), X-ray diffraction, Fourier Transform Raman spectroscopy, and inductively coupled plasma atomic emission spectroscopy (ICP-AES) to establish their chemical composition, crystallinity and size distribution. The coatings of the four chewing gums differ chemically from each other, and more specifically the amount of TiO 2 varies from one coating to another. TiO 2 particles constitute the entire coating of some chewing gums, whereas for others, TiO 2 particles are embedded in an organic matrix and/or mixed with minerals like calcium carbonate, talc, or magnesium silicate. We found 1.1 ± 0.3 to 17.3 ± 0.9 mg TiO 2 particles per piece of chewing gum, with a mean diameter of 135 ± 42 nm. TiO 2 nanoparticles account for 19 ± 4% of all particles, which represents a mass fraction of 4.2 ± 0.1% on average. The intake of nanoparticles is thus highly dependent on the kind of chewing gum, with an estimated range extending from 0.04 ± 0.01 to 0.81 ± 0.04 mg of nano-TiO 2 per piece of chewing gum. These data should serve to refine the exposure scenario.

Titanium dioxide (TiO 2 ) is a transition metal oxide widely used as a white pigment in various applications, including food. Due to the classification of TiO 2 nanoparticles by the International Agency for Research on Cancer as potentially harmful for humans by inhalation, the presence of nanoparticles in food products needed to be confirmed by a set of independent studies. Seven samples of food-grade TiO 2 (E171) were extensively characterised for their size distribution, crystallinity and surface properties by the currently recommended methods. All investigated E171 samples contained a fraction of nanoparticles, however, below the threshold defining the labelling of nanomaterial. On the basis of these results and a statistical analysis, E171 food-grade TiO 2 totally differs from the reference material P25, confirming the few published data on this kind of particle. Therefore, the reference material P25 does not appear to be the most suitable model to study the fate of food-grade TiO 2 in the gastrointestinal tract. The criteria currently to obtain a representative food-grade sample of TiO 2 are the following: (1) crystalline-phase anatase, (2) a powder with an isoelectric point very close to 4.1, (3) a fraction of nanoparticles comprised between 15% and 45%, and (4) a low specific surface area around 10 m 2  g - 1 .

Drug delivery systems are proposed for the in situ controlled delivery of therapeutic molecules in the scope of tissue engineering. We propose herein silica nanofibers as carriers for the loading and release of bioactive proteins. The influence of pH, time and concentration on the amount of adsorbed proteins was studied. The interactions allowing loading were then studied by means of electron microscopy, zeta potential measurements, electron energy loss spectroscopy and attenuated total reflectance Fourier transform infrared analysis. Release profiles were determined and biological activities were enzymatically assessed. The first part of the work was carried out with lysozyme as a model protein, and then bioactive growth factors TGF-β1 and GDF-5 were used because their significance in human adipose stromal cell differentiation towards intervertebral disc nucleopulpocytes was previously assessed. It is demonstrated that protein-silica nanofiber interactions are mainly driven by hydrogen bonds and local electrostatic interactions. The present data thus provide a better understanding of the adsorption phenomenon involved, as well as a method to control protein adsorption and release. It is worth pointing out that the kinetic release of growth factors, up to 28 days, and their biological activity maintenance seem to be compatible with intervertebral disc regenerative medicine.

A systematic study was carried out on monolayer films and lipid vesicles to elucidate the interactions between membrane lipids and commercial particles of titanium dioxide TiO2 (TiO2-P25). Pressure-area isotherms of lipids at various pH values were recorded on a Langmuir trough with or without TiO2-P25 and NaCl in the subphase. Electrophoretic mobilities of lipid vesicles and TiO2-P25 particles were measured to identify the pH range where attractive electrostatic interactions between lipids and TiO2-P25 could take place. The results show that (i) the surface of TiO2-P25 particles interacts only with some phospholipids, (ii) the driving forces are electrostatic and (iii) non-electrostatic interactions were also observed, depending on the molecular structure. More precisely, the phospholipids 1,2-dimyristoyl-sn-glycero-3-phosphate monosodium salt (DMPA), 1,2-dimyristoyl-sn-glycero-3-phospho-rac-1-glycerol (DMPG) and 1',3'-bis[1,2-dimyristoyl-sn-glycero-3-phospho]-sn-glycerol (TMCL) interacted strongly with the TiO2-P25 surface through electrostatic interactions, providing they were oppositely charged, i.e. for pH between 2 and 6.6. For TMCL and DMPG, interactions with the surface of TiO2-P25 in non-favourable electrostatic conditions, suggested another kind of binding, probably through the hydroxyl groups of the terminal glycerol. Weaker attractive interactions were demonstrated for 1,2-dimyristoyl-sn-glycero-3-phospho-l-serine (DMPS) and the synthetic lipid dihexadecyl phosphate (DHP). For DMPS, the carboxylate group is involved in the adsorption onto TiO2. The other membrane lipids such as 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE) and sphingomyelin (SM) did not interact with TiO2-P25 regardless of pH., (Copyright © 2014 Elsevier B.V. All rights reserved.)