Regional differences in three-dimensional fiber organization, smooth muscle cell phenotype, and contractility in the pregnant mouse cervix.

The orientation and function of smooth muscle in the cervix may contribute to the important biomechanical properties that change during pregnancy. Thus, this study examined the three-dimensional structure, smooth muscle phenotype, and mechanical and contractile functions of the upper and lower cervix of nongravid (not pregnant) and gravid (pregnant) mice. In gravid cervix, we uncovered region-specific changes in the structure and organization of fiber tracts.

Polymer nanodiscs support the functional extraction of an artificial transmembrane cytochrome.

Polymer nanodiscs are an attractive alternative to surfactants for studying integral membrane proteins within their native lipid environment. Here, we investigate the use of such polymers to isolate a computationally-designed de novo membrane cytochrome named CytbX. We show that the block copolymers known as CyclAPols can efficiently extract CytbX directly from biomembranes and are compatible with the downstream purification and biophysical characterisation of this artificial protein.

Delineating redox cooperativity in water-soluble and membrane multiheme cytochromes through protein design.

Nature has evolved diverse electron transport proteins and multiprotein assemblies essential to the generation and transduction of biological energy. However, substantially modifying or adapting these proteins for user-defined applications or to gain fundamental mechanistic insight can be hindered by their inherent complexity. De novo protein design offers an attractive route to stripping away this confounding complexity, enabling us to probe the fundamental workings of these bioenergetic proteins and systems, while providing robust, modular platforms for constructing completely artificial electron-conducting circuitry.

Computational design of de novo bioenergetic membrane proteins.

The major energy-producing reactions of biochemistry occur at biological membranes. Computational protein design now provides the opportunity to elucidate the underlying principles of these processes and to construct bioenergetic pathways on our own terms. Here, we review recent achievements in this endeavour of 'synthetic bioenergetics', with a particular focus on new enabling tools that facilitate the computational design of biocompatible de novo integral membrane proteins.

Long-term functional outcomes in polytrauma: a fundamentally new approach is needed in prediction.

Purpose: Modern trauma care has reduced mortality but poor long-term outcomes with low follow-up rates are common with limited recommendations for improvements. The aim of this study was to describe the impact of severe injury on the health-related quality of life, specifically characterise the non-responder population and to identify modifiable predictors of poorer outcomes.

Methods: Five-year (2012-2016) prospective cohort study was performed at a level 1 trauma centre.

The outcomes of the most severe polytrauma patients: a systematic review of the use of high ISS cutoffs for performance measurement.

Background: This systematic review aimed to describe the outcomes of the most severely injured polytrauma patients and identify the consistent Injury Severity Score based definition of utilised for their definition. This could provide a global standard for trauma system benchmarking.

Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was applied to this review.

An expandable, modular de novo protein platform for precision redox engineering.

The electron-conducting circuitry of life represents an as-yet untapped resource of exquisite, nanoscale biomolecular engineering. Here, we report the characterization and structure of a de novo diheme "maquette" protein, 4D2, which we subsequently use to create an expanded, modular platform for heme protein design. A well-folded monoheme variant was created by computational redesign, which was then utilized for the experimental validation of continuum electrostatic redox potential calculations.

Experimental demonstration of diffusion limitations on resolution and SNR in MR microscopy.

Purpose: MR microscopy is in principle capable of producing images at cellular resolution (<10 µm), but various factors limit the quality achieved in practice. A recognized limit on the signal to noise ratio and spatial resolution is the dephasing of transverse magnetization caused by diffusion of spins in strong gradients. Such effects may be reduced by using phase encoding instead of frequency encoding read-out gradients.

Cellular production of a de novo membrane cytochrome.

Heme-containing integral membrane proteins are at the heart of many bioenergetic complexes and electron transport chains. The importance of these electron relay hubs across biology has inspired the design of de novo proteins that recreate their core features within robust, versatile, and tractable protein folds. To this end, we report here the computational design and in-cell production of a minimal diheme membrane cytochrome which successfully integrates into the cellular membrane of live bacteria.

Trends in polytrauma incidence among major trauma admissions.

Purpose: Polytrauma is increasingly recognized as a disease beyond anatomical injuries. Due to population growth, centralization, and slow uptake of preventive measures, major trauma presentations in most trauma systems show a slow but steady increase. The proportional contribution of polytrauma patients to this increase is unknown.

Computational modelling of diatom silicic acid transporters predicts a conserved fold with implications for their function and evolution.

Diatoms are an important group of algae that can produce intricate silicified cell walls (frustules). The complex process of silicification involves a set of enigmatic integral membrane proteins that are thought to actively transport the soluble precursor of biosilica, dissolved silicic acid. Full-length silicic acid transporters are found widely across the diatoms while homologous shorter proteins have now been identified in a range of other organisms.

The most critically injured polytrauma patient mortality: should it be a measurement of trauma system performance?

Purpose: The risk of death after traumatic injury in developed trauma systems is at an all-time low. Among 'major trauma' patients (injury severity score, ISS > 15), the risk of dying is less than 10%. This group contains critical polytrauma patients (ISS 50-75), with high risks of death.

Bench to bore ramifications of inter-subject head differences on RF shimming and specific absorption rates at 7T.

Purpose: This study shows how inter-subject variation over a dataset of 72 head models results in specific absorption rate (SAR) and B field homogeneity differences using common shim scenarios.

Methods: MR-CT datasets were used to segment 71 head models into 10 tissue compartments. These head models were affixed to the shoulders and neck of the virtual family Duke model and placed within an 8 channel transmit surface-loop array to simulate the electromagnetic fields of a 7T imaging experiment.

Surviving severe COVID-19: Interviews with patients, informal carers and health professionals.

Background: The COVID-19 pandemic has been associated with an unprecedented number of critical care survivors. Their experiences through illness and recovery are likely to be complex, but little is known about how best to support them.

Aim: This study aimed to explore experiences of illness and recovery from the perspective of survivors, their relatives and professionals involved in their care.

Using Smartwatches to Observe Changes in Activity During Recovery From Critical Illness Following COVID-19 Critical Care Admission: 1-Year, Multicenter Observational Study.

Background: As a sequela of the COVID-19 pandemic, a large cohort of critical illness survivors have had to recover in the context of ongoing societal restrictions.

Objective: We aimed to use smartwatches (Fitbit Charge 3; Fitbit LLC) to assess changes in the step counts and heart rates of critical care survivors following hospital admission with COVID-19, use these devices within a remote multidisciplinary team (MDT) setting to support patient recovery, and report on our experiences with this.

Methods: We conducted a prospective, multicenter observational trial in 8 UK critical care units.

Small-residue packing motifs modulate the structure and function of a minimal de novo membrane protein.

Alpha-helical integral membrane proteins contain conserved sequence motifs that are known to be important in helix packing. These motifs are a promising starting point for the construction of artificial proteins, but their potential has not yet been fully explored. Here, we study the impact of introducing a common natural helix packing motif to the transmembrane domain of a genetically-encoded and structurally dynamic de novo membrane protein.

Magnetic resonance imaging of mean cell size in human breast tumors.

Purpose: Cell size is a fundamental characteristic of all tissues, and changes in cell size in cancer reflect tumor status and response to treatments, such as apoptosis and cell-cycle arrest. Unfortunately, cell size can currently be obtained only by pathological evaluation of tumor tissue samples obtained invasively. Previous imaging approaches are limited to preclinical MRI scanners or require relatively long acquisition times that are impractical for clinical imaging.

Traumatic haemopneumothorax and 'whole-body' subcutaneous emphysema: successful use of a small-bore chest drain.

A 56-year-old man presented having had two falls at home. He had a background of multiple sclerosis. After his second fall, during which he had fallen onto the toilet injuring his right chest, he was brought into the emergency department reporting pleuritic chest discomfort.

Influence of the timing of internal fixation of femur fractures during shock resuscitation on remote organ damage.

Background: Reamed intramedullary nailing is the gold standard for management of femur fractures. Nailing within 24 h is proven to reduce complications from ongoing bleeding, soft-tissue damage and pain. However, when combined with haemorrhagic shock, femur fracture and intramedullary nailing are associated with immune-mediated damage to remote organs.

Cell necrosis-independent sustained mitochondrial and nuclear DNA release following trauma surgery.

Background: Mitochondrial DNA (mtDNA), a potent proinflammatory damage-associated molecular pattern, is released in large titers following trauma. The effect of trauma surgery on mtDNA concentration is unknown. We hypothesized that mtDNA and nuclear DNA (nDNA) levels would increase proportionately with the magnitude of surgery and both would then decrease rapidly.

The impact of specialist trauma service on major trauma mortality.

Introduction: Trauma services throughout the world have had positive effects on trauma-related mortality. Australian trauma services are generally more consultative in nature rather than the North American model of full trauma admission service. We hypothesized that the introduction of a consultative specialist trauma service in a Level I Australian trauma center would reduce mortality of the severely injured.

Epidemiology of acute transfusions in major orthopaedic trauma.

Objectives: The orthopaedic trauma-related blood product usage is largely unknown. Aim of this study was to describe the epidemiology of early (<24 hours of arrival) blood component use in major orthopaedic trauma.

Design: 12-month prospective observational study.

Tissue oxygen saturation changes during intramedullary nailing of lower-limb fractures.

Background: The systemic complications of acute intramedullary nailing (IMN) in trauma patients are well known. There are no reliable methods available to predict these adverse outcomes. Noninvasive near-infrared spectroscopy (NIRS) allows measurement of oxygen saturation within muscle tissue (StO2) and quantification of the potential metabolic and microcirculatory effects of IMN in real time.