The solution structure of the disulphide-linked homodimer of the human trefoil protein TFF1

AbstractThe trefoil factor family protein, TFF1, forms a homodimer, via a disulphide linkage, that has greater activity in wound healing assays than the monomer. Having previously determined a high-resolution solution structure of a monomeric analogue of TFF1, we now investigate the structure of the homodimer formed by the native sequence. The two putative receptor/ligand recognition domains are found to be well separated, at opposite ends of a flexible linker. This contrasts sharply with the known fixed and compact arrangement of the two trefoil domains of the closely related TFF2, and has significant implications for the mechanism of action and functional specificity of the TFF of proteins

Instream wood increases riverbed temperature variability in a lowland sandy stream

The (re)introduction of wood into rivers is becoming increasingly popular in river restoration and natural flood management schemes. While instream wood is known to promote geomorphic and hydraulic diversity, the impact of wood in driving surface water‐streambed exchange and subsequent streambed temperatures remains under‐researched, particularly in lowland rivers. We make use of the occurrence of three naturally occurring wood structures in a small, lowland sandy stream to determine how the presence of wood alters the geomorphic, hydraulic and thermal properties of the streambed. Our results show that instream wood plays an important role in promoting localized geomorphic complexity and thermal variation in the streambed. Locations within and immediately downstream of wood structures displayed the highest temperature range and daily variation. Locations upstream of wood structures were characterized by weaker daily temperature variation, while areas without wood displayed relatively stable streambed temperatures, with little diurnal fluctuation. Our study indicates that at this lowland site, instream wood increased seasonal temperature extremes (increased summer and decreased winter temperatures) at shallow depths by enhancing infiltration of warmer (summer) and colder (winter) surface water. This reduction in thermal buffering is likely to have significant implications to streambed‐dwelling communities and highlights that the thermal impacts of wood reintroduction in lowland rivers should be considered prior to river restoration

Duke Activity Status Index and Liver Frailty Index predict mortality in ambulatory patients with advanced chronic liver disease:A prospective, observational study

BACKGROUND: There remains a lack of consensus on how to assess functional exercise capacity and physical frailty in patients with advanced chronic liver disease (CLD) being assessed for liver transplantation (LT). Aim To investigate prospectively the utility of the Duke Activity Status Index (DASI) and Liver Frailty Index (LFI) in ambulatory patients with CLD.AIM: To investigate prospectively the utility of the Duke Activity Status Index (DASI) and Liver Frailty Index (LFI) in ambulatory patients with CLD.METHODS: We recruited patients from outpatient clinics at University Hospitals Birmingham, UK (2018-2019). We prospectively collated the DASI and LFI to identify the prevalence of, respectively, functional capacity and physical frailty, and to evaluate their accuracy in predicting overall and pre-LT mortality.RESULTS: We studied 307 patients (57% male; median age 54 years; UKELD 52). Median DASI score was 28.7 (IQR 16.2-50.2), mean LFI was 3.82 (SD = 0.72), and 81% were defined either 'pre-frail' or 'frail'. Female sex and hyponatraemia were significant independent predictors of both DASI and LFI. Age and encephalopathy were significant independent predictors of LFI, while BMI significantly predicted DASI. DASI and LFI were significantly related to overall (HR 0.97, p = 0.001 [DASI], HR 2.04, p = 0.001 [LFI]) and pre-LT mortality (HR 0.96, p = 0.02 [DASI], HR 1.94, p = 0.04 [LFI]).CONCLUSIONS: Poor functional exercise capacity and physical frailty are highly prevalent among ambulatory patients with CLD who are being assessed for LT. The DASI and LFI are simple, low-cost tools that predict overall and pre-LT mortality. Implementation of both should be considered in all outpatients with CLD to highlight those who may benefit from targeted nutritional and exercise interventions.</p

Duke Activity Status Index and Liver Frailty Index predict mortality in ambulatory patients with advanced chronic liver disease:A prospective, observational study

BACKGROUND: There remains a lack of consensus on how to assess functional exercise capacity and physical frailty in patients with advanced chronic liver disease (CLD) being assessed for liver transplantation (LT). Aim To investigate prospectively the utility of the Duke Activity Status Index (DASI) and Liver Frailty Index (LFI) in ambulatory patients with CLD.AIM: To investigate prospectively the utility of the Duke Activity Status Index (DASI) and Liver Frailty Index (LFI) in ambulatory patients with CLD.METHODS: We recruited patients from outpatient clinics at University Hospitals Birmingham, UK (2018-2019). We prospectively collated the DASI and LFI to identify the prevalence of, respectively, functional capacity and physical frailty, and to evaluate their accuracy in predicting overall and pre-LT mortality.RESULTS: We studied 307 patients (57% male; median age 54 years; UKELD 52). Median DASI score was 28.7 (IQR 16.2-50.2), mean LFI was 3.82 (SD = 0.72), and 81% were defined either 'pre-frail' or 'frail'. Female sex and hyponatraemia were significant independent predictors of both DASI and LFI. Age and encephalopathy were significant independent predictors of LFI, while BMI significantly predicted DASI. DASI and LFI were significantly related to overall (HR 0.97, p = 0.001 [DASI], HR 2.04, p = 0.001 [LFI]) and pre-LT mortality (HR 0.96, p = 0.02 [DASI], HR 1.94, p = 0.04 [LFI]).CONCLUSIONS: Poor functional exercise capacity and physical frailty are highly prevalent among ambulatory patients with CLD who are being assessed for LT. The DASI and LFI are simple, low-cost tools that predict overall and pre-LT mortality. Implementation of both should be considered in all outpatients with CLD to highlight those who may benefit from targeted nutritional and exercise interventions.</p

Droplet Microfluidic Optimisation Using Micropipette Characterisation of Bio-Instructive Polymeric Surfactants

Droplet microfluidics can produce highly tailored microparticles whilst retaining monodispersity. However, these systems often require lengthy optimisation, commonly based on a trial-and-error approach, particularly when using bio-instructive, polymeric surfactants. Here, micropipette manipulation methods were used to optimise the concentration of bespoke polymeric surfactants to produce biodegradable (poly(d,l-lactic acid) (PDLLA)) microparticles with unique, bio-instructive surface chemistries. The effect of these three-dimensional surfactants on the interfacial tension of the system was analysed. It was determined that to provide adequate stabilisation, a low level (0.1% (w/v)) of poly(vinyl acetate-co-alcohol) (PVA) was required. Optimisation of the PVA concentration was informed by micropipette manipulation. As a result, successful, monodisperse particles were produced that maintained the desired bio-instructive surface chemistry

Epidemiological analysis of the first 1000 cases of SARS-CoV-2 lineage BA.1 (B.1.1.529, Omicron) compared with co-circulating Delta in Wales, UK

Background The Omicron (lineage B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wales, UK, on 3 December 2021. The aim of the study was to describe the first 1000 cases of the Omicron variant by demographic, vaccination status, travel and severe outcome status and compare this to contemporaneous cases of the Delta variant. Methods Testing, typing and contact tracing data were collected by Public Health Wales and analysis undertaken by the Communicable Disease Surveillance Centre (CDSC). Risk ratios for demographic factors and symptoms were calculated comparing Omicron cases to Delta cases identified over the same time period. Results By 14 December 2021, 1000 cases of the Omicron variant had been identified in Wales. Of the first 1000, just 3% of cases had a prior history of travel revealing rapid community transmission. A higher proportion of Omicron cases were identified in individuals aged 20–39, and most cases were double vaccinated (65.9%) or boosted (15.7%). Age-adjusted analysis also revealed that Omicron cases were less likely to be hospitalised (0.4%) or report symptoms (60.8%). Specifically a significant reduction was observed in the proportion of Omicron cases reporting anosmia (8.9%). Conclusion Key findings include a lower risk of anosmia and a reduced risk of hospitalisation in the first 1000 Omicron cases compared with co-circulating Delta cases. We also identify that existing measures for travel restrictions to control importations of new variants identified outside the United Kingdom did not prevent the rapid ingress of Omicron within Wales

Ink-jet 3D printing as a strategy for developing bespoke non-eluting biofilm resistant medical devices

Chronic infection as a result of bacterial biofilm formation on implanted medical devices is a major global healthcare problem requiring new biocompatible, biofilm-resistant materials. Here we demonstrate how bespoke devices can be manufactured through ink-jet-based 3D printing using bacterial biofilm inhibiting formulations without the need for eluting antibiotics or coatings. Candidate monomers were formulated and their processability and reliability demonstrated. Formulations for in vivo evaluation of the 3D printed structures were selected on the basis of their in vitro bacterial biofilm inhibitory properties and lack of mammalian cell cytotoxicity. In vivo in a mouse implant infection model, Pseudomonas aeruginosa biofilm formation on poly-TCDMDA was reduced by ∼99% when compared with medical grade silicone. Whole mouse bioluminescence imaging and tissue immunohistochemistry revealed the ability of the printed device to modulate host immune responses as well as preventing biofilm formation on the device and infection of the surrounding tissues. Since 3D printing can be used to manufacture devices for both prototyping and clinical use, the versatility of ink-jet based 3D-printing to create personalised functional medical devices is demonstrated by the biofilm resistance of both a finger joint prosthetic and a prostatic stent printed in poly-TCDMDA towards P. aeruginosa and Staphylococcus aureus

Inkjet based 3D Printing of bespoke medical devices that resist bacterial biofilm formation

We demonstrate the formulation of advanced functional 3D printing inks that prevent the formation of bacterial biofilms in vivo. Starting from polymer libraries, we show that a biofilm resistant object can be 3D printed with the potential for shape and cell instructive function to be selected independently. When tested in vivo, the candidate materials not only resisted bacterial attachment but drove the recruitment of host defences in order to clear infection. To exemplify our approach, we manufacture a finger prosthetic and demonstrate that it resists biofilm formation – a cell instructive function that can prevent the development of infection during surgical implantation. More widely, cell instructive behaviours can be ‘dialled up’ from available libraries and may include in the future such diverse functions as the modulation of immune response and the direction of stem cell fate

2-Acetyl­pyridinium bromanilate

In the crystal of the title mol­ecular salt (systematic name: 2-acetyl­pyridinium 2,5-dibromo-4-hydr­oxy-3,6-dioxocyclo­hexa-1,4-dienolate), C7H8NO+·C6HBr2O4 −, centrosymmetric rings consisting of two cations and two anions are formed, with the components linked by alternating O—H⋯O and N—H⋯O hydrogen bonds. Short O⋯Br contacts [3.243 (2) and 3.359 (2) Å] may help to consolidate the packing