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We evaluated the impact of COVID-19 restriction on the angioplasty service and outcome of chronic limb-threatening ischaemia (CLTI) patients undergoing lower-limb angioplasty in a UK secondary care setting. Consecutive patients were analysed retrospectively. Pre-COVID-19 (08/2018–02/2020), 106 CLTI patients (91% Fontaine 4; 60% diabetes mellitus) and during COVID-19 (03/2020–07/2021) 94 patients were treated (86% Fontaine 4; 66% diabetes mellitus). While the average monthly number of patients treated did not change, the proportion of day cases significantly increased (53% to 80%), and hospitalised patients decreased. Patients treated in ≤14/5 days after referral significantly increased to 64/63%. Kaplan–Meier survival analysis (30-day/1-year) showed that neither wound healing nor mortality were significantly changed during COVID-19. In day cases, 1-year but not 30-day major amputations significantly increased, and clinically driven target-lesion revascularisation decreased during COVID-19. One-year mortality was significantly worse in hospitalised compared to day cases (14% vs. 43%) at similar wound healing rates (83% vs. 84%). The most frequent known cause of death was infectious disease (64%), while cardiovascular (21%) was less frequent. Despite COVID-19 restrictions, a safe and effective angioplasty service was maintained while shortening waiting times. Very high mortality rates in hospitalised patients may indicate that CLTI patients need to be referred and treated more aggressively earlier.

Several factors have limited the potential/application of self-propelled chemical motors. Here, to address some of these concerns, the authors report on the development of squid-derived biodegradable motors, which use an anaesthetic metabolite for propulsion and demonstrate a range of different applications.

Wireless magnetic microrobots are envisioned to revolutionize minimally invasive medicine. While many promising medical magnetic microrobots are proposed, the ones using hard magnetic materials are not mostly biocompatible, and the ones using biocompatible soft magnetic nanoparticles are magnetically very weak and, therefore, difficult to actuate. Thus, biocompatible hard magnetic micro/nanomaterials are essential toward easy‐to‐actuate and clinically viable 3D medical microrobots. To fill such crucial gap, this study proposes ferromagnetic and biocompatible iron platinum (FePt) nanoparticle‐based 3D microprinting of microrobots using the two‐photon polymerization technique. A modified one‐pot synthesis method is presented for producing FePt nanoparticles in large volumes and 3D printing of helical microswimmers made from biocompatible trimethylolpropane ethoxylate triacrylate (PETA) polymer with embedded FePt nanoparticles. The 30 μm long helical magnetic microswimmers are able to swim at speeds of over five body lengths per second at 200 Hz, making them the fastest helical swimmer in the tens of micrometer length scale at the corresponding low‐magnitude actuation fields of 5–10 mT. It is also experimentally in vitro verified that the synthesized FePt nanoparticles are biocompatible. Thus, such 3D‐printed microrobots are biocompatible and easy to actuate toward creating clinically viable future medical microrobots.

Magnetic microswimmers are promising devices for biomedical and environmental applications. Bacterium flagella‐inspired magnetic microhelices with perpendicular magnetizations are currently considered standard for propulsion at low Reynolds numbers because of their well‐understood dynamics and controllability. Deviations from this system have recently emerged: randomly shaped magnetic micropropellers with nonlinear swimming behaviors show promise in sensing, sorting, and directional control. The current progresses in 3D micro/nanoprinting allow the production of arbitrary 3D microstructures, increasing the accessible deterministic design space for complex micropropeller morphologies. Taking advantage of this, a shape is systematically reproduced that was formerly identified while screening randomly shaped propellers. Its nonlinear behavior, which is called frequency‐induced reversal of swimming direction (FIRSD), allows a propeller to swim in opposing directions by only changing the applied rotating field's frequency. However, the identically shaped swimmers do not only display the abovementioned swimming property but also exhibit a variety of swimming behaviors that are shown to arise from differences in their magnetic moment orientations. This underlines not only the role of shape in microswimmer behavior but also the importance of determining magnetic properties of future micropropellers that act as intelligent devices, as single‐shape templates with different magnetic moments can be utilized for different operation modes.

An individual’s sodium to potassium intake ratio (Na:K) has been shown to be an important predictor of hypertension. The aim of this study was to estimate the mean 24 h urinary Na, K and Na:K of Irish adults and to identify the foods that determine Na:K in a nationally representative sample of Irish adults. This study was based on data from the Irish National Adult Nutrition Survey (2008–2010) (NANS), which collected spot urine samples and dietary data in a nationally representative sample of Irish adults aged 18+ years. The mean urinary molar Na:K of Irish men and women was 1.90 and 2.15, respectively, which exceed target molar ratios of ≤1.0 and ≤2.0. The mean estimated 24-h urinary excretion of Na was 4631 mg for men and 3525 mg for women, which exceed target maximum population intakes for all gender and age groups. The mean estimated 24-h urinary excretion of K was 3894 mg for men and 2686 mg for women, with intakes in women of all ages and older men (65+ years) below current recommendations. The key foods positively associated with a lower Na:K were fruits, vegetables, potatoes, breakfast cereals, milk, yogurt and fresh meat, while the foods negatively associated with a lower Na:K were breads, cured and processed meats and butters and fat spreads. Strategies to reduce sodium and increase potassium intakes are necessary to lower population Na:K, which may help to reduce the burden of hypertension-related diseases in the Irish population.

We evaluated the impact of COVID-19 restriction on the angioplasty service and outcome of chronic limb-threatening ischaemia (CLTI) patients undergoing lower-limb angioplasty in a UK secondary care setting. Consecutive patients were analysed retrospectively. Pre-COVID-19 (08/2018–02/2020), 106 CLTI patients (91% Fontaine 4; 60% diabetes mellitus) and during COVID-19 (03/2020–07/2021) 94 patients were treated (86% Fontaine 4; 66% diabetes mellitus). While the average monthly number of patients treated did not change, the proportion of day cases significantly increased (53% to 80%), and hospitalised patients decreased. Patients treated in ≤14/5 days after referral significantly increased to 64/63%. Kaplan–Meier survival analysis (30-day/1-year) showed that neither wound healing nor mortality were significantly changed during COVID-19. In day cases, 1-year but not 30-day major amputations significantly increased, and clinically driven target-lesion revascularisation decreased during COVID-19. One-year mortality was significantly worse in hospitalised compared to day cases (14% vs. 43%) at similar wound healing rates (83% vs. 84%). The most frequent known cause of death was infectious disease (64%), while cardiovascular (21%) was less frequent. Despite COVID-19 restrictions, a safe and effective angioplasty service was maintained while shortening waiting times. Very high mortality rates in hospitalised patients may indicate that CLTI patients need to be referred and treated more aggressively earlier. [ABSTRACT FROM AUTHOR]

Microswimmers are smart devices with potential applications in medicine and biotechnology at the micrometer-scale. Magnetic micropropellers with their remote control via rotating magnetic fields are especially auspicious. Helicoidal propellers with a linear velocity–frequency dependence emerged as the standard propulsion mechanism over the last decade. However, with their functions becoming more pivotal on the way to practical uses, deviations in shape and swimming behavior are inevitable. Consequently, propellers with nonlinear velocity–frequency relationships arise that not only pose different challenges but also offer advanced possibilities. The most critical nonlinearities are the wobbling behavior with its solution branching that has potential for bimodal swimming and the swimming characteristics in the step-out regime that are essential for selection and swarm control. Here, we show experimentally and with numerical calculations how the previously unpredictable branching can be controlled and, thus, becomes utilizable with an example 3D-printed swimmer device. Additionally, we report how two step-out modes arise for propellers with a nonlinear velocity–frequency dependence that have the potential to accelerate future microswimmer sorting procedures. [ABSTRACT FROM AUTHOR]

Wireless magnetic microrobots are envisioned to revolutionize minimally invasive medicine. While many promising medical magnetic microrobots are proposed, the ones using hard magnetic materials are not mostly biocompatible, and the ones using biocompatible soft magnetic nanoparticles are magnetically very weak and, therefore, difficult to actuate. Thus, biocompatible hard magnetic micro/nanomaterials are essential toward easy‐to‐actuate and clinically viable 3D medical microrobots. To fill such crucial gap, this study proposes ferromagnetic and biocompatible iron platinum (FePt) nanoparticle‐based 3D microprinting of microrobots using the two‐photon polymerization technique. A modified one‐pot synthesis method is presented for producing FePt nanoparticles in large volumes and 3D printing of helical microswimmers made from biocompatible trimethylolpropane ethoxylate triacrylate (PETA) polymer with embedded FePt nanoparticles. The 30 μm long helical magnetic microswimmers are able to swim at speeds of over five body lengths per second at 200 Hz, making them the fastest helical swimmer in the tens of micrometer length scale at the corresponding low‐magnitude actuation fields of 5–10 mT. It is also experimentally in vitro verified that the synthesized FePt nanoparticles are biocompatible. Thus, such 3D‐printed microrobots are biocompatible and easy to actuate toward creating clinically viable future medical microrobots. [ABSTRACT FROM AUTHOR]

Magnetic microswimmers are promising devices for biomedical and environmental applications. Bacterium flagella‐inspired magnetic microhelices with perpendicular magnetizations are currently considered standard for propulsion at low Reynolds numbers because of their well‐understood dynamics and controllability. Deviations from this system have recently emerged: randomly shaped magnetic micropropellers with nonlinear swimming behaviors show promise in sensing, sorting, and directional control. The current progresses in 3D micro/nanoprinting allow the production of arbitrary 3D microstructures, increasing the accessible deterministic design space for complex micropropeller morphologies. Taking advantage of this, a shape is systematically reproduced that was formerly identified while screening randomly shaped propellers. Its nonlinear behavior, which is called frequency‐induced reversal of swimming direction (FIRSD), allows a propeller to swim in opposing directions by only changing the applied rotating field's frequency. However, the identically shaped swimmers do not only display the abovementioned swimming property but also exhibit a variety of swimming behaviors that are shown to arise from differences in their magnetic moment orientations. This underlines not only the role of shape in microswimmer behavior but also the importance of determining magnetic properties of future micropropellers that act as intelligent devices, as single‐shape templates with different magnetic moments can be utilized for different operation modes. [ABSTRACT FROM AUTHOR]

Magnetic microrobots that swim through liquid media are of interest for minimally invasive medical procedures, bioengineering, and manufacturing. Many of the envisaged applications, such as micromanipulation and targeted cargo delivery, necessitate the use and adequate control of multiple microrobots, which will increase the velocity, robustness, and efficacy of a procedure. While various methods involving heterogeneous geometries, magnetic properties, and surface chemistries have been proposed to enhance independent control, the main challenge has been that the motion between all microswimmers remains coupled through the global control signal of the magnetic field. Katsamba and Lauga [Phys. Rev. Appl. 5, 064019 (2016)] proposed transchiral microrobots, a theoretical design with magnetized spirals of opposite handedness. The competition between the spirals can be tuned to give an intrinsic nonlinearity that each device can function only within a given band of frequencies. This allows individual microrobots to be selectively controlled by varying the frequency of the rotating magnetic field. Here, we present the experimental realization and characterization of transchiral micromotors composed of independently driven magnetic helices. We show a swimming micromotor that yields negligible net motion until a critical frequency is reached and a micromotor that changes its translation direction as a function of the frequency of the rotating magnetic field. This work demonstrates a crucial step toward completely decoupled and addressable swimming magnetic microrobots. [ABSTRACT FROM AUTHOR]

Bacteria-propelled biohybrid microswimmers have recently shown to be able to actively transport and deliver cargos encapsulated into their synthetic constructs to specific regions locally. However, usage of synthetic materials as cargo carriers can result in inferior performance in load-carrying efficiency, biocompatibility, and biodegradability, impeding clinical translation of biohybrid microswimmers. Here, we report construction and external guidance of bacteria-driven microswimmers using red blood cells (RBCs; erythrocytes) as autologous cargo carriers for active and guided drug delivery. Multifunctional biohybrid microswimmers were fabricated by attachment of RBCs [loaded with anticancer doxorubicin drug molecules and superparamagnetic iron oxide nanoparticles (SPIONs)] to bioengineered motile bacteria, Escherichia coli MG1655, via biotin-avidin-biotin binding complex. Autonomous and on-board propulsion of biohybrid microswimmers was provided by bacteria, and their external magnetic guidance was enabled by SPIONs loaded into the RBCs. Furthermore, bacteria-driven RBC microswimmers displayed preserved deformability and attachment stability even after squeezing in microchannels smaller than their sizes, as in the case of bare RBCs. In addition, an on-demand light-activated hyperthermia termination switch was engineered for RBC microswimmers to control bacteria population after operations. RBCs, as biological and autologous cargo carriers in the biohybrid microswimmers, offer notable advantages in stability, deformability, biocompatibility, and biodegradability over synthetic cargo-carrier materials. The biohybrid microswimmer design presented here transforms RBCs from passive cargo carriers into active and guidable cargo carriers toward targeted drug and other cargo delivery applications in medicine. [ABSTRACT FROM AUTHOR]

The introduction of mandatory margining for non-cleared derivatives portfolios has major implications for the pricing and risk measurement of over-the-counter (OTC) derivatives. In particular, a model for estimating future initial margin requirements is necessary to enable the calculation of relevant pricing adjustments, net counterparty credit exposures and credit capital requirements. Existing literature on the topic suggests a model that makes use of regression techniques, but little detail is available on the predictive quality of these models within a Monte Carlo simulation framework. We review these regression-based initial margin models in detail and compare their output against the actual margin requirements measured by the International Swaps and Derivatives Association standard initial margin model (ISDA SIMM) methodology. We observe that the models generally perform well for single trades but show some degradation for larger diversified portfolios. We investigate potential extensions and improvements to the model, along with examining some additional 'conservatism' features that may have application in the context of credit exposure measurement. The initial margin modelling approaches discussed here are similarly applicable to centrally cleared or exchange-traded portfolios. [ABSTRACT FROM AUTHOR]

Untethered micron-scale mobile robots can navigate and non-invasively perform specific tasks inside unprecedented and hard-to-reach inner human body sites and inside enclosed organ-on-a-chip microfluidic devices with live cells. They are aimed to operate robustly and safely in complex physiological environments where they will have a transforming impact in bioengineering and healthcare. Research along this line has already demonstrated significant progress, increasing attention, and high promise over the past several years. The first-generation microrobots, which could deliver therapeutics and other cargo to targeted specific body sites, have just been started to be tested inside small animals toward clinical use. Here, we review frontline advances in design, fabrication, and testing of untethered mobile microrobots for bioengineering applications. We convey the most impactful and recent strategies in actuation, mobility, sensing, and other functional capabilities of mobile microrobots, and discuss their potential advantages and drawbacks to operate inside complex, enclosed and physiologically relevant environments. We lastly draw an outlook to provide directions in the veins of more sophisticated designs and applications, considering biodegradability, immunogenicity, mobility, sensing, and possible medical interventions in complex microenvironments. [ABSTRACT FROM AUTHOR]

At the sub-millimeter scale, capillary forces enable robust and reversible adhesion between biological organisms and varied substrates. Current human-engineered mobile untethered micromanipulation systems rely on forces which scale poorly or utilize gripper-part designs that promote manipulation. Capillary forces, alternatively, are dependent upon the surface chemistry (which is scale independent) and contact perimeter, which conforms to the part surface. We report a mobile capillary microgripper that is able to pick and place parts of various materials and geometries, and is thus ideal for microassembly tasks that cannot be accomplished by large tethered manipulators. We achieve the programmable assembly of sub-millimeter parts in an enclosed three-dimensional aqueous environment by creating a capillary bridge between the targeted part and a synthetic, untethered, mobile body. The parts include both hydrophilic and hydrophobic components: hydrogel, kapton, human hair, and biological tissue. The 200 μm untethered system can be controlled with five-degrees-of-freedom and advances progress towards autonomous desktop manufacturing for tissue engineering, complex micromachines, microfluidic devices, and meta-materials. [ABSTRACT FROM AUTHOR]

Existing remotely actuated magnetic microrobots exhibit a maximum of only five-degree-of-freedom (DOF) actuation, as creation of a driving torque about the microrobot magnetization axis is not achievable. This lack of full orientation control limits the effectiveness of existing microrobots for precision tasks of object manipulation and orientation for advanced medical, biological and micromanufacturing applications. This paper presents a magnetic actuation method that allows remotely powered microrobots to achieve full six-DOF actuation by considering the case of a non-uniform magnetization profile within the microrobot body. This non-uniform magnetization allows for additional rigid-body torques to be induced from magnetic forces via a moment arm. A general analytical model presents the working principle for continuous and discrete magnetization profiles, which is applied to permanent or non-permanent (soft) magnet bodies. Several discrete-magnetization designs are also presented which possess reduced coupling between magnetic forces and induced rigid-body torques. Design guidelines are introduced which can be followed to ensure that a magnetic microrobot design is capable of six-DOF actuation. A simple permanent-magnet prototype is fabricated and used to quantitatively demonstrate the accuracy of the analytical model in a constrained-DOF environment and qualitatively for free motion in a viscous liquid three-dimensional environment. Results show that desired forces and torques can be created with high precision and limited parasitic actuation, allowing for full six-DOF actuation using limited feedback control. [ABSTRACT FROM AUTHOR]