Nanomedicine, Nanotechnology in medicine

27 pages, 10 figures, 26 referencesInternational audienceNanomedicine is a relatively new field of science and technology. It looks sometimes ill defined and interpretations of that term may vary, especially between Europe and the United States. By interacting with biological molecules, therefore at nanoscale, nanotechnology opens up a vast field of research and application. Interactions between artificial molecular assemblies or nanodevices and biomolecules can be understood both in the extracellular medium and inside the human cells. Operating at nanoscale allow to exploit physical properties different from those observed at microscale such as the volume/surface ratio. The investigated diagnostic applications can be considered for in vitro as well as for in vivo diagnosis. In vitro, the synthesized particles and manipulation or detection devices allow for the recognition, capture, and concentration of biomolecules. In vivo, the synthetic molecular assemblies are mainly designed as a contrast agent for imaging. A second area exhibiting a strong development is the "nanodrugs" where nanoparticles are designed for targeted drug delivery. The use of such carriers improves the drug biodistribution, targeting active molecules to diseased tissues while protecting healthy tissue. A third area of application is regenerative medicine where nanotechnology allows developing biocompatible materials which support growth of cells used in cell therapy. The application of nanotechnology to medicine raises new issues because of new uses they allow, for instance: Is the power of these new diagnostics manageable by the medical profession? What means treating a patient without any clinical signs? Nanomedicine can contribute to the development of a personalized medicine both for diagnosis and therapy. There exists in many countries existing regulatory frameworks addressing the basic rules of safety and effectiveness of nanotechnology based medicine, whether molecular assemblies or medical devices. But there is a need to clarify or to modify these regulations which mobilize many experts. France is a country where the medical development of nanotechnology is significant, like Germany, the United Kingdom or Spain, as regards the European Union. There is an active scientific community and industrial partners of all sizes, even if the technology transfer to industry is not as effective as in North America

Automated telephone communication systems for preventive healthcare and management of long-term conditions

Background Automated telephone communication systems (ATCS) can deliver voice messages and collect health-related information from patients using either their telephone’s touch-tone keypad or voice recognition software. ATCS can supplement or replace telephone contact between health professionals and patients. There are four different types of ATCS: unidirectional (one-way, non-interactive voice communication), interactive voice response (IVR) systems, ATCS with additional functions such as access to an expert to request advice (ATCS Plus) and multimodal ATCS, where the calls are delivered as part of a multicomponent intervention. Objectives To assess the effects of ATCS for preventing disease and managing long-term conditions on behavioural change, clinical, process, cognitive, patient-centred and adverse outcomes. Search methods We searched 10 electronic databases (the Cochrane Central Register of Controlled Trials; MEDLINE; Embase; PsycINFO; CINAHL; Global Health; WHOLIS; LILACS; Web of Science; and ASSIA); three grey literature sources (Dissertation Abstracts, Index to Theses, Australasian Digital Theses); and two trial registries (www.controlled-trials.com; www.clinicaltrials.gov) for papers published between 1980 and June 2015. Selection criteria Randomised, cluster- and quasi-randomised trials, interrupted time series and controlled before-and-after studies comparing ATCS interventions, with any control or another ATCS type were eligible for inclusion. Studies in all settings, for all consumers/carers, in any preventive healthcare or long term condition management role were eligible. Data collection and analysis We used standard Cochrane methods to select and extract data and to appraise eligible studies. Main results We included 132 trials (N = 4,669,689). Studies spanned across several clinical areas, assessing many comparisons based on evaluation of different ATCS types and variable comparison groups. Forty-one studies evaluated ATCS for delivering preventive healthcare, 84 for managing long-term conditions, and seven studies for appointment reminders. We downgraded our certainty in the evidence primarily because of the risk of bias for many outcomes. We judged the risk of bias arising from allocation processes to be low for just over half the studies and unclear for the remainder. We considered most studies to be at unclear risk of performance or detection bias due to blinding, while only 16% of studies were at low risk. We generally judged the risk of bias due to missing data and selective outcome reporting to be unclear. For preventive healthcare, ATCS (ATCS Plus, IVR, unidirectional) probably increase immunisation uptake in children (risk ratio (RR) 1.25, 95% confidence interval (CI) 1.18 to 1.32; 5 studies, N = 10,454; moderate certainty) and to a lesser extent in adolescents (RR 1.06, 95% CI 1.02 to 1.11; 2 studies, N = 5725; moderate certainty). The effects of ATCS in adults are unclear (RR 2.18, 95% CI 0.53 to 9.02; 2 studies, N = 1743; very low certainty). For screening, multimodal ATCS increase uptake of screening for breast cancer (RR 2.17, 95% CI 1.55 to 3.04; 2 studies, N = 462; high certainty) and colorectal cancer (CRC) (RR 2.19, 95% CI 1.88 to 2.55; 3 studies, N = 1013; high certainty) versus usual care. It may also increase osteoporosis screening. ATCS Plus interventions probably slightly increase cervical cancer screening (moderate certainty), but effects on osteoporosis screening are uncertain. IVR systems probably increase CRC screening at 6 months (RR 1.36, 95% CI 1.25 to 1.48; 2 studies, N = 16,915; moderate certainty) but not at 9 to 12 months, with probably little or no effect of IVR (RR 1.05, 95% CI 0.99, 1.11; 2 studies, 2599 participants; moderate certainty) or unidirectional ATCS on breast cancer screening. Appointment reminders delivered through IVR or unidirectional ATCS may improve attendance rates compared with no calls (low certainty). For long-term management, medication or laboratory test adherence provided the most general evidence across conditions (25 studies, data not combined). Multimodal ATCS versus usual care showed conflicting effects (positive and uncertain) on medication adherence. ATCS Plus probably slightly (versus control; moderate certainty) or probably (versus usual care; moderate certainty) improves medication adherence but may have little effect on adherence to tests (versus control). IVR probably slightly improves medication adherence versus control (moderate certainty). Compared with usual care, IVR probably improves test adherence and slightly increases medication adherence up to six months but has little or no effect at longer time points (moderate certainty). Unidirectional ATCS, compared with control, may have little effect or slightly improve medication adherence (low certainty). The evidence suggested little or no consistent effect of any ATCS type on clinical outcomes (blood pressure control, blood lipids, asthma control, therapeutic coverage) related to adherence, but only a small number of studies contributed clinical outcome data. The above results focus on areas with the most general findings across conditions. In condition-specific areas, the effects of ATCS varied, including by the type of ATCS intervention in use. Multimodal ATCS probably decrease both cancer pain and chronic pain as well as depression (moderate certainty), but other ATCS types were less effective. Depending on the type of intervention, ATCS may have small effects on outcomes for physical activity, weight management, alcohol consumption, and diabetes mellitus. ATCS have little or no effect on outcomes related to heart failure, hypertension, mental health or smoking cessation, and there is insufficient evidence to determine their effects for preventing alcohol/ substance misuse or managing illicit drug addiction, asthma, chronic obstructive pulmonary disease, HIV/AIDS, hypercholesterolaemia, obstructive sleep apnoea, spinal cord dysfunction or psychological stress in carers. Only four trials (3%) reported adverse events, and it was unclear whether these were related to the intervention

On the issue of transparency and reproducibility in nanomedicine.

Following our call to join in the discussion over the suitability of implementing a reporting checklist for bio-nano papers, the community responds

In Situ Ultrafast 2D NMR Spectroelectrochemistry for Real-Time Monitoring of Redox Reactions

The in situ implementation of an electrochemical cell (EC) inside a nuclear magnetic resonance (NMR) spectrometer is extremely powerful to study redox reactions in real time and identify unstable reaction intermediates. Unfortunately, the implementation of an electrochemical device near the sensitive volume of an NMR probe significantly affects the quality of the NMR signal, inducing significant line broadening resulting in peak overlap and partial loss of the multiplet structures. Two-dimensional (2D) NMR spectroscopy allows one to bypass signal overlapping by spreading the peaks along two orthogonal dimensions, while providing precious information in terms of structural elucidation. Nevertheless, the acquisition of 2D NMR data suffers from long acquisition durations which are incompatible with fast redox processes taking place in solution. Here, we present a new approach to deal with this issue, consisting of coupling EC-NMR with ultrafast 2D spectroscopy, capable of recording 2D spectra much faster than conventional 2D NMR. This approach is applied to the real-time monitoring of a model reaction. Fast correlation spectroscopy (COSY) spectra are recorded every 3 min in the course of the 80 min reaction, leading to the unambiguous identification of one reaction intermediate and two reaction products. The evolution of 2D NMR peak volumes in the course of time provides further insight into the mechanism of this reaction involving an unstable intermediate. This study demonstrates the feasibility and the relevance of coupling in situ spectroelectrochemistry with ultrafast 2D spectroscopy to monitor real-time electrochemical reactions in the NMR tube

Fast Quantitative H-1-C-13 Two-Dimensional NMR with Very High Precision

Quantitative analysis by nuclear magnetic resonance (NMR) requires highly precise measurements to achieve reliable quantification. It is particularly true in C-13 site-specific natural isotope fractionation studied by nuclear magnetic resonance, where the range of values of C-13 isotopic deviations at natural abundance is highly restricted. Consequently, an NMR method capable of measuring delta C-13 parts per thousand values with a very high precision (a few per mil) is indispensable. This high degree of precision has already been achieved by one-dimensional C-13 acquisitions; however, this approach is limited by peak overlaps which reduce the precision of the isotope content determination, even for certain small molecules. It is therefore necessary to extend this promising methodology to a higher dimensionality. In this context, this paper aims at determining conditions that allow the achievement of two-dimensional (2D) H-1-C-13 heteronuclear experiments with a precision of a few per mil in a reasonable time. Our results demonstrate that a high precision (repeatability of 2 per mil) can be reached with the H-1-C-13 HSQC (Heteronuclear Single Quantum Correlation) experiment, thus satisfying the conditions needed to perform C-13 isotope analysis by 2D NMR. We also consider the impact of several approaches which have been proposed to reduce the duration of heteronuclear 2D experiments. Two of these common time-saving strategies, spectral aliasing and linear prediction, are fully compatible with the high-precision requirements of isotopic NMR, while a third one, nonuniform sampling, leads to dramatic precision losses. In conclusion, this study demonstrates the feasibility of very precise 2D NMR measurements and opens a number of application perspectives

Optimization of the preparation of aqueous suspensions of waxy maize starch nanocrystals using a response surface methodology

International audienceResponse surface methodology was used to investigate the effect of five selected factors on the selective H2SO4 hydrolysis of waxy maize starch granules. These predictors were temperature, acid concentration, starch concentration, hydrolysis duration, and stirring speed. The goal of this study was to optimize the preparation of aqueous suspensions of starch nanocrystals, i.e., to determine the operative conditions leading to the smallest size of insoluble hydrolyzed residue within the shortest time and with the highest yield. Therefore empirical models were elaborated for the hydrolysis yield and the size of the insoluble residues using a central composite face design involving 31 trials. They allowed us to show that it was possible to obtain starch nanocrystals after only 5 days of H2SO4 hydrolysis with a yield of 15 wt % and having the same shape as those obtained from the classical procedure after 40 days of HCl treatment, with a yield of 0.5 wt %

Fast Spatially Encoded 3D NMR Strategies for C-13-Based Metabolic Flux Analysis

The measurement of site-specific C-13 enrichments in complex mixtures of C-13-labeled metabolites is a powerful tool for metabolic flux analysis. One of the main methods to measure such enrichments is homonuclear H-1 2D NMR However, the major limitation of this technique is the acquisition time, which can amount to a few hours. This drawback was recently overcome by the design of fast COSY experiments for measuring specific C-13-enrichments, based on single-scan 2D NMR However, these experiments are still limited by overlaps because of H-1-C-13 splittings, thus limiting the metabolic information accessible for complex biological mixtures. To circumvent this limitation, we propose to tilt the H-1-C-13 coupling into a third dimension via fast-hybrid 3D NMR methods combining the speed of ultrafast 2D NMR with the high resolution of conventional methods. Two strategies are described that allow the acquisition of a complete 3D J-resolved-COSY spectrum in 12 min (for concentrations as low as 10 mM). The analytical potentialities of both methods are evaluated on a series of C-13-enriched glucose samples and on a biomass hydrolyzate obtained from Escherichia coli cells. Once optimized, the two complementary experiments lead to a trueness and a precision of a few percent and an excellent linearity. The advantages and drawbacks of these approaches are discussed and their potentialities are highlighted