The biocompatibility of biofuel cells operating inside the body.

In 1968 Wolfson et al. published the concept for producing energy inside the body using catalytic electrodes exposed to the body fluid as an electrolyte and utilising naturally occurring fuels such as glucose. Since then, the technology has advanced to enhance the levels of power using enzymes immobilised within three-dimensional bioelectrodes that are nanostructured. Current research in the field of enzymatic fuel cells is directed toward applying electrochemical and nanostructural expertise to increase the energy density, to increase the power density, to increase the operational stability, and to increase the voltage output. Nonetheless, biocompatibility remains the major challenge for increasing the life-time for implanted enzymatic biofuel cells. Here, we discuss the current issues for biocompatibility and suggest directions to enhance the design of biofuel cells so as to increase the life-time of implantation whilst maintaining sufficient performance to provide power for implanted medical devices.

Cell-free production of VDAC directly into liposomes for integration with biomimetic membrane systems.

The mitochondrial voltage-dependent anion channel (VDAC) is a pivotal protein since it provides the major transport pathway between the cytosol and the mitochondrial intermembrane space and it is implicated in cell apoptosis by functioning as a gatekeeper for the trafficking of mitochondrial death molecules. VDAC is a beta-barrel channel with a large conductance, and we use it as a model transport protein for the design of biomimetic systems. To overcome the limitations of classical overexpression methods for producing and purifying membrane proteins (MPs) we describe here the use of an optimized cell-free system. In a one-step reaction VDAC is obtained directly integrated into liposomes and purified by ultracentrifugation. We then combine proteoliposomes with different bilayers models in order to validate VDAC insertion and functionality. This VDAC biomimetic model is the first example validating the use of a cell-free expression system for production of MPs into liposomes and tethered bilayers as a toolbox to build a wide range of biomimetic devices.

An ethically guided preclinical device for phenotyping H2 production in laboratory rodents.

BACKGROUND: Dihydrogen (H2) is produced endogenously by the intestinal microbiota through the fermentation of diet carbohydrates. Over the past few years, numerous studies have demonstrated the significant therapeutic potential of H2 in various pathophysiological contexts, making the characterization of its production in laboratory species of major preclinical importance. METHODS: This study proposes an innovative solution to accurately monitor H2 production in free-moving rodents while respecting animal welfare standards. The developed device consisted of a wire rodent cage placed inside an airtight chamber in which the air quality was maintained, and the H2 concentration was continuously analyzed. After the airtightness and efficiency of the systems used to control and maintain air quality in the chamber were checked, tests were carried out on rats and mice with different metabolic phenotypes, over 12 min to 1-h experiments and repeatedly. H2 production rates (HPR) were obtained using an easy calculation algorithm based on a first-order moving average. RESULTS: HPR in hyperphagic Zucker rats was found to be twice as high as in control Wistar rats, respectively, 2.64 and 1.27 nmol.s-1 per animal. In addition, the ingestion of inulin, a dietary fiber, stimulated H2 production in mice. HPRs were 0.46 nmol.s-1 for animals under control diet and 1.99 nmol.s-1 for animals under inulin diet. CONCLUSIONS: The proposed device coupled with our algorithm enables fine analysis of the metabolic phenotype of laboratory rats or mice with regard to their endogenous H2 production.

Molecular Hydrogen for Outpatients with COVID-19 (Hydro-COVID): A Phase 3 Randomised, Triple-Blinded, Pragmatic, Placebo-Controlled, Multicentre Trial.

Background. Due to its antioxidant, anti-inflammatory, anti-apoptosis, and anti-fatigue properties, molecular hydrogen (H2) is potentially a novel therapeutic nutrient for patients with coronavirus acute disease 2019 (COVID-19). We determined the efficacy and safety profile of hydrogen-rich water (HRW) to reduce the risk of COVID-19 progression. Methods: We also conducted a phase 3, triple-blind, randomised, placebo-controlled trial to evaluate treatment with HRW initiated within 5 days after the onset of signs or symptoms in primary care patients with mild-to-moderate, laboratory-confirmed COVID-19. Participants were randomised to receive HRW or placebo twice daily for 21 days. The incidence of clinical worsening and adverse events were the primary endpoints. Results: A total of 675 participants were followed up to day 30. HRW was not superior to placebo in preventing clinical worsening at day 14: in H2 group, 46.1% in the H2 group, 43.5% in the placebo group, hazard ratio 1.09, 90% confidence interval [0.90-1.31]. One death was reported at day 30 in the H2 group and two in the placebo group at day 30. Adverse events were reported in 91 (27%) and 89 (26.2%) participants, respectively. Conclusions: HRW taken twice daily from the onset of COVID-19 symptoms for 21 days did not reduce clinical worsening.

Hydrogen inhalation: in vivo rat genotoxicity tests.

Preclinical and clinical studies have shown that molecular hydrogen (H2) has anti-oxidant, anti-inflammatory, and anti-apoptotic properties. Safety data are available in the literature and acute toxicity has been tested in isolated cells and laboratory animals. We have evaluates the genotoxicity of H2 in vivo in rats after 72 h exposure, following the International Council for Harmonization guidelines ICH S2 (R1). The study was conducted on three groups of male Wistar rats: a negative control group, a positive control group receiving methyl methanesulfonate, and a H2-treated group receiving a 3.1% H2 gas mixture for 72 h. Alkaline comet, formamidopyrimidine DNA glycosylase (Fpg)-modified comet and bone marrow micronucleus assays were performed. H2 exposure increased neither comet-tail DNA intensity (DNA damage) nor frequency of "hedgehogs" in blood, liver, lungs, or bronchoalveolar lavage fluid. No increase in Fpg-sensitive sites in lungs, no induction of micronucleus formation, and no imbalance of immature erythrocyte to total erythrocyte ratio (IME%) was observed in rats exposed to H2. The ICH S2 (R1) test-battery revealed no in vivo genotoxicity in Wistar rats after 72 h inhalation of a mixture containing 3.1% H2.

Comparison of Trunk Motion between Moderate AIS and Healthy Children.

Analysis of kinematic and postural data of adolescent idiopathic scoliosis (AIS) patients seems relevant for a better understanding of biomechanical aspects involved in AIS and its etiopathogenesis. The present project aimed at investigating kinematic differences and asymmetries in early AIS in a static task and in uniplanar trunk movements (rotations, lateral bending, and forward bending). Trunk kinematics and posture were assessed using a 3D motion analysis system and a force plate. A total of fifteen healthy girls, fifteen AIS girls with a left lumbar main curve, and seventeen AIS girls with a right thoracic main curve were compared. Statistical analyses were performed to investigate presumed differences between the three groups. This study showed kinematic and postural differences between mild AIS patients and controls such as static imbalance, a reduced range of motion in the frontal plane, and a different kinematic strategy in lateral bending. These differences mainly occurred in the same direction, whatever the type of scoliosis, and suggested that AIS patients behave similarly from a dynamic point of view.

Reuse of medical face masks in domestic and community settings without sacrificing safety: Ecological and economical lessons from the Covid-19 pandemic.

The need for personal protective equipment increased exponentially in response to the Covid-19 pandemic. To cope with the mask shortage during springtime 2020, a French consortium was created to find ways to reuse medical and respiratory masks in healthcare departments. The consortium addressed the complex context of the balance between cleaning medical masks in a way that maintains their safety and functionality for reuse, with the environmental advantage to manage medical disposable waste despite the current mask designation as single-use by the regulatory frameworks. We report a Workflow that provides a quantitative basis to determine the safety and efficacy of a medical mask that is decontaminated for reuse. The type IIR polypropylene medical masks can be washed up to 10 times, washed 5 times and autoclaved 5 times, or washed then sterilized with radiations or ethylene oxide, without any degradation of their filtration or breathability properties. There is loss of the anti-projection properties. The Workflow rendered the medical masks to comply to the AFNOR S76-001 standard as "type 1 non-sanitory usage masks". This qualification gives a legal status to the Workflow-treated masks and allows recommendation for the reuse of washed medical masks by the general population, with the significant public health advantage of providing better protection than cloth-tissue masks. Additionally, such a legal status provides a basis to perform a clinical trial to test the masks in real conditions, with full compliance with EN 14683 norm, for collective reuse. The rational reuse of medical mask and their end-of-life management is critical, particularly in pandemic periods when decisive turns can be taken. The reuse of masks in the general population, in industries, or in hospitals (but not for surgery) has significant advantages for the management of waste without degrading the safety of individuals wearing reused masks.

Towards a metadata registry for evaluating augmented medical interventions.

Quality evaluation in the field of Augmented Surgery is strategic for public health policies. It implies to be able to effectively perform evaluation of Quality in term of Expected Medical Benefit (EMB). The notion of EMB is complex and not standardized in this field. To define and to evaluate EMB, it is necessary to discover the knowledge on the domain targeted by the device and to structure it. This paper presents first parts of this work. Focused on navigated knee surgery, it led us to obtain two main results: the identification of a new criterion for evaluating EMB obtained thanks to the formalization of a new kind of metadata. These encouraging results seem to offer new perspectives for the evaluation of devices from the field of augmented surgery.

Long duration stabilization of porous silicon membranes in physiological media: Application for implantable reactors.

The natural biodegradabilty of porous silicon (pSi) in physiological media limits its wider usage for implantable systems. We report the stabilization of porous silicon (pSi) membranes by chemical surface oxidation using RCA1 and RCA2 protocols, which was followed by a PEGylation process using a silane-PEG. These surface modifications stabilized the pSi to allow a long period of immersion in PBS, while leaving the pSi surface sufficiently hydrophilic for good filtration and diffusion of several biomolecules of different sizes without any blockage of the pSi structure. The pore sizes of the pSi membranes were between 5 and 20 nm, with the membrane thickness around 70 µm. The diffusion coefficient for fluorescein through the membrane was 2 × 10-10 cm2 s-1, and for glucose was 2.2 × 10-9 cm2 s-1. The pSi membrane maintained that level of glucose diffusion for one month of immersion in PBS. After 2 months immersion in PBS the pSi membrane continued to operate, but with a reduced glucose diffusion coefficient. The chemical stabilization of pSi membranes provided almost 1 week stable and functional biomolecule transport in blood plasma and opens the possibility for its short-term implantation as a diffusion membrane in biocompatible systems.

Controlled Heat and Humidity-Based Treatment for the Reuse of Personal Protective Equipment: A Pragmatic Proof-of-Concept to Address the Mass Shortage of Surgical Masks and N95/FFP2 Respirators and to Prevent the SARS-CoV2 Transmission.

Background: The coronavirus infectious disease-2019 (COVID-19) pandemic has led to an unprecedented shortage of healthcare resources, primarily personal protective equipment like surgical masks, and N95/filtering face piece type 2 (FFP2) respirators. Objective: Reuse of surgical masks and N95/FFP2 respirators may circumvent the supply chain constraints and thus overcome mass shortage. Methods, design, setting, and measurement: Herein, we tested the effects of dry- and moist-air controlled heating treatment on structure and chemical integrity, decontamination yield, and filtration performance of surgical masks and FFP2 respirators. Results: We found that treatment in a climate chamber at 70°C during 1 h with 75% humidity rate was adequate for enabling substantial decontamination of both respiratory viruses, oropharyngeal bacteria, and model animal coronaviuses, while maintaining a satisfying filtering capacity. Limitations: Further studies are now required to confirm the feasibility of the whole process during routine practice. Conclusion: Our findings provide compelling evidence for the recycling of pre-used surgical masks and N95/FFP2 respirators in case of imminent mass shortfall.

A PANI supported lipid bilayer that contains NhaA transporter proteins provides a basis for a biomimetic biocapacitor.

We designed a supported lipid bilayer (SLB) biomimetic membrane system that comprised polyaniline (PANI) to support a lipid bilayer membrane that incorporated Na+/H+ transporter proteins (NhaA) to give the system the capability of controllable electrogenic ion transport. The high turnover rate of NhaA (∼105 per min) provides the basis for this PANI-SLB-NhaA system to be a high-speed rechargeable biocapacitor that functions as a low-energy-consuming fast switch for biological engineering applications.

Fan-Beam Based Virtual Fluoroscopy for Navigated Catheterization in Interventional Radiology.

Personalized medicine implies reducing invasiveness of therapeutic procedures. Although interventional radiology proved a very interesting alternative to surgical procedures, it still raises concerns due to the irradiation dose received by the medical team (and by the patient). We propose a novel concept allowing to reduce very significantly the irradiation dose during the phases where tools inserted in the patient have to be tracked with respect to previously acquired images. This implies inserting a miniaturized X-ray detector in the tip of the tools, and reducing the dose by a "rotating collimator". We demonstrate that real-time processing of the signals allows accurate localization of the tip of the tools, with a dose reduction of at least ten times.

A novel bimodal stethoscope for gastric collection of heart sounds: preliminary results.

Heart sound analysis is commonly used by physicians during auscultations to evaluate cardiac activity as a first line. These sounds originate from heartbeats and the resulting blood flow, and can provide important information about heart function and hemodynamics. The monitoring of heart sounds in patients suffering from chronic cardiac pathologies can be useful to detect or prevent cardiac events. For this purpose, a bimodal implanted gastric stethoscope was developed allowing home monitoring of electrophysiological and mechanical parameters.An in-vivo experiment in pigs was carried out to validate the feasibility of heart sound detection from an accelerometer embedded in a stethoscope prototype implanted in the submucosal layer of the gastric wall. Data recorded over several weeks validate the tolerance and the sensitivity of the device. These promising preliminary results confirm the interest of considering the stomach as a strategic implantation site for heart sound monitoring.

Tackling the Concept of Symbiotic Implantable Medical Devices with Nanobiotechnologies.

This review takes an approach to implanted medical devices that considers whether the intention of the implanted device is to have any communication of energy or materials with the body. The first part describes some specific examples of three different classes of implants, analyzed with regards to the type of signal sent to cells. Through several examples, the authors describe that a one way signaling to the body leads to encapsulation or degradation. In most cases, those phenomena do not lead to major problems. However, encapsulation or degradation are critical for new kinds of medical devices capable of duplex communication, which are defined in this review as symbiotic devices. The concept the authors propose is that implanted medical devices that need to be symbiotic with the body also need to be designed with an intended duplex communication of energy and materials with the body. This extends the definition of a biocompatible system to one that requires stable exchange of materials between the implanted device and the body. Having this novel concept in mind will guide research in a new field between medical implant and regenerative medicine to create actual symbiotic devices.

Comparison of the goals and MISTELS scores for the evaluation of surgeons on training benches.

PURPOSE: Evaluation of surgical technical abilities is a major issue in minimally invasive surgery. Devices such as training benches offer specific scores to evaluate surgeons but cannot transfer in the operating room (OR). A contrario, several scores measure performance in the OR, but have not been evaluated on training benches. Our aim was to demonstrate that the GOALS score, which can effectively grade in the OR the abilities involved in laparoscopy, can be used for evaluation on a laparoscopic testbench (MISTELS). This could lead to training systems that can identify more precisely the skills that have been acquired or must still be worked on. METHODS: 32 volunteers (surgeons, residents and medical students) performed the 5 tasks of the MISTELS training bench and were simultaneously video-recorded. Their performance was evaluated with the MISTELS score and with the GOALS score based on the review of the recording by two experienced, blinded laparoscopic surgeons. The concurrent validity of the GOALS score was assessed using Pearson and Spearman correlation coefficients with the MISTELS score. The construct validity of the GOALS score was assessed with k-means clustering and accuracy rates. Lastly, abilities explored by each MISTELS task were identified with multiple linear regression. RESULTS: GOALS and MISTELS scores are strongly correlated (Pearson correlation coefficient = 0.85 and Spearman correlation coefficient = 0.82 for the overall score). The GOALS score proves to be valid for construction for the tasks of the training bench, with a better accuracy rate between groups of level after k-means clustering, when compared to the original MISTELS score (accuracy rates, respectively, 0.75 and 0.56). CONCLUSION: GOALS score is well suited for the evaluation of the performance of surgeons of different levels during the completion of the tasks of the MISTELS training bench.

Challenges for successful implantation of biofuel cells.

There is a growing interest in the design and engineering of operational biofuel cells that can be implanted. This review highlights the recent progress in the electrochemistry of biofuel cell technologies, but with a particular emphasis on the medical and physiological aspects that impact the biocompatibility of biofuel cells operating inside a living body. We discuss the challenge of supplying power to implantable medical devices, with regard to the limitations of lithium battery technology and why implantable biofuel cells can be a promising alternative to provide the levels of power required for medical devices. In addition to the challenge of designing a biofuel cell that provides a stable level of sufficient power, the review highlights the biocompatibility and biofouling problems of implanting a biofuel cell that have a major impact on the availability of the substrates inside body that provide fuel for the biofuel cell. These physiological challenges and associated ethical considerations are essential to consider for biofuel cells that are designed to be implanted for long-term operation inside a living animal and eventually to human clinical applications.

Evaluation of the Needle Positioning Accuracy of a Light Puncture Robot Under MRI Guidance: Results of a Clinical Trial on Healthy Volunteers.

PURPOSE: To assess the accuracy of Light Puncture Robot (LPR) as a patient-mounted robot, in positioning a sham needle under MRI guidance for abdominal percutaneous interventions. MATERIALS AND METHODS: This monocentric, prospective and non-controlled study was approved by the ethics review board. The study evaluated the accuracy of LPR V3 to achieve a virtual puncture in 20 healthy volunteers. Three trajectories were tried on each volunteer, under 3-T MRI guidance. RESULTS: Accuracy under 5 mm in attaining a 10 cm-deep target was reached in 72% of attempts after 2 robot motions with a median error of 4.1 mm [2.1; 5.1]. Median procedure time for one trajectory was 12.9 min [10.2; 18.0] and median installation time was 9.0 min [6.0; 13.0]. CONCLUSION: LPR accuracy in the deployment of a sham needle inside the MRI tunnel and its setup time are promising. Further studies need to be conducted to confirm these results before clinical trials.

Development of miniaturized light endoscope-holder robot for laparoscopic surgery.

PURPOSE: We have conducted experiments with an innovatively designed robot endoscope holder for laparoscopic surgery that is small and low cost. MATERIALS AND METHODS: A compact light endoscope robot (LER) that is placed on the patient's skin and can be used with the patient in the lateral or dorsal supine position was tested on cadavers and laboratory pigs in order to allow successive modifications. The current control system is based on voice recognition. The range of vision is 360 degrees with an angle of 160 degrees . Twenty-three procedures were performed. RESULTS: The tests made it possible to advance the prototype on a variety of aspects, including reliability, steadiness, ergonomics, and dimensions. The ease of installation of the robot, which takes only 5 minutes, and the easy handling made it possible for 21 of the 23 procedures to be performed without an assistant. CONCLUSION: The LER is a camera holder guided by the surgeon's voice that can eliminate the need for an assistant during laparoscopic surgery. The ease of installation and manufacture should make it an effective and inexpensive system for use on patients in the lateral and dorsal supine positions. Randomized clinical trials will soon validate a new version of this robot prior to marketing.

Accessing the influence of repositioning on the pelvis' 3-D orientation in wheelchair users.

This study aimed at evaluating the effects of mechanical repositioning, obtained by the increase in seat-to-back (STB) and system tilt angles, on the position of the pelvis with spinal-cord injured subjects seated in a wheelchair. The noninvasive method used combined magnetic resonance imaging (MRI) images of the whole pelvis obtained in a supine posture and ultrasound images of the pelvic iliac crests obtained in four seating positions. The matching of the two image data sets enabled the location of fourteen pelvic landmarks in the seated positions. From these landmarks, the pelvic tilt, obliquity, and transverse rotation, and the three-dimensional (3-D) motion of the pelvis were calculated. Results showed that the increase in STB angle is not equal to the calculated increase in pelvic tilt and that the pelvis rotated posteriorly, moved forward and downwards. An increase in the system tilt moved the pelvis rearwards and downwards, which counter-balanced the movement seen with the increase in STB. At the return to the first position, no significant changes were observed in the pelvis' position and orientation compared to the initial posture. Results also demonstrated the importance in calculating the total 3-D rotations and translations to characterize adequately the pelvic movement.