Making a case for outpatient parenteral antimicrobial therapy (OPAT).

In the wake of the COVID-19 pandemic, and its negative impact on both acute and elective care and decline in available inpatient resources, there is an imperative to maximize safe and effective alternatives to inpatient hospital care. Properly governed outpatient parenteral antimicrobial therapy (OPAT) services embed the principles of antimicrobial stewardship (AMS) (including use of early oral therapy) and support admission avoidance and early discharge for a growing range of patient groups with complex infections through well-organized multidisciplinary team working. Expansion of OPAT aligns with the UK's national strategy to deliver care closer to home and cost-effectively maximize use of inpatient resources. OPAT serves as an exemplar to other ambulatory services and presents opportunities for developing and assuring AMS strategies within the rapidly developing hospital-at-home and virtual ward environments.

Supported Biomembrane Systems Incorporating Multiarm Polymers and Bioorthogonal Tethering.

To functionalize interfaces with supported biomembranes and membrane proteins, the challenge is to build stabilized and supported systems that mimic the native lipid microenvironment. Our objective is to control substrate-to-biomembrane spacing and the tethering chemistry so proteoliposomes can be fused and conjugated without perturbation of membrane protein function. Furthermore, the substrates need to exhibit low protein and antibody nonspecific binding to use these systems in assays. We have employed protein orthogonal coupling schemes in concert with multiarm poly(ethylene glycol) (PEG) technology to build supported biomembranes on microspheres. The lipid bilayer structures and tailored substrates of the microsphere-supported biomembranes were analyzed via flow cytometry, confocal fluorescence, and super-resolution imaging microscopy, and the lateral fluidity was quantified using fluorescence recovery after photobleaching (FRAP) techniques. Under these conditions, the 4-arm-PEG20,000-NH2 based configuration gave the most desirable tethering system based on lateral diffusivity and coverage.

Investigation of Head Kinematics and Brain Strain Response During Soccer Heading Using a Custom-Fit Instrumented Mouthguard.

Association football, also known as soccer in some regions, is unique in encouraging its participants to intentionally use their head to gain a competitive advantage, including scoring a goal. Repetitive head impacts are now being increasingly linked to an inflated risk of developing long-term neurodegenerative disease. This study investigated the effect of heading passes from different distances, using head acceleration data and finite element modelling to estimate brain injury risk. Seven university-level participants wore a custom-fitted instrumented mouthguard to capture linear and angular acceleration-time data. They performed 10 headers within a laboratory environment, from a combination of short, medium, and long passes. Kinematic data was then used to calculate peak linear acceleration, peak angular velocity, and peak angular acceleration as well as two brain injury metrics: head injury criterion and rotational injury criterion. Six degrees of freedom acceleration-time data were also inputted into a widely accepted finite element brain model to estimate strain-response using mean peak strain and cumulative strain damage measure values. Five headers were considered to have a 25% concussion risk. Mean peak linear acceleration equalled 26 ± 7.9 g, mean peak angular velocity 7.20 ± 2.18 rad/s, mean peak angular acceleration 1730 ± 611 rad/s2, and 95th percentile mean peak strain 0.0962 ± 0.252. Some of these data were similar to brain injury metrics reported from American football, which supports the need for further investigation into soccer heading.

Nitric oxide: a major determinant of mast cell phenotype and function

Mast cells (MC) are important in the numerous physiological processes of homeostasis and disease. Most notably, MC are critical effectors in the development and exacerbation of allergic disorders. Nitric oxide (NO) is a diatomic radical produced by nitric oxide synthase (NOS), and has pluripotent cell signaling and cytotoxic properties. NO can influence many MC functions. Recent evidence shows the source of this NO can be from the mast cell itself. Governing the production of this endogenous NO, through alterations in the expression of tetrahydrobiopterin (BH4), a NOS cofactor, has stabilizing effects on MC degranulation. Furthermore, NO regulates the synthesis and secretion of de novo generated mediators, including leukotrienes and chemokines. These novel observations add to the growing body of knowledge surrounding the role of NO in the MC.