Truth in the Dark

It is never dark here. We know shadow and grey, but not pitch or black

The assessment of physical frailty and physical activity in end-stage liver disease

Physical frailty in end-stage liver disease (ESLD) is prevalent across North America and has a negative impact on clinical outcomes, yet little is known about the prevalence of physical frailty in ESLD within the United Kingdom (UK). Physical activity and exercise-based interventions seem a plausible option to improve physical frailty, yet there is limited understanding of current habitual physical activity levels in ESLD. Consequently, research studies to date have based interventions around well recognised National guidelines designed for healthy individuals or those with other chronic diseases. Effectiveness of, and adherence to, these interventions have been varied, limiting the translation of research findings into clinical practice. Through a prospective UK-based observational cohort study, I identified high prevalence (80%) of, and the clinical characteristics (i.e. age and hyponatraemia) that predict, physical frailty in ESLD. Furthermore, the quick and simple to use outcome measures, Liver Frailty Index (LFI) and Duke Activity Status Index, were validated for overall and waiting list mortality in patients assessed for liver transplantation (LT). Understanding the volume and intensity distribution of physical activity in those with ESLD will help guide future study interventions. As part of our wider observational case-control sarcopenia study, I highlighted the negative discrepancy between volume, and distribution of activity intensity, by using remotely-monitored wrist-worn accelerometery of patients with well-characterised ESLD compared to age/sex matched healthy controls. In particular, those with ESLD did not sustain activity at a moderate intensity for longer than one minute indicating that current exercise advice for those with ESLD (5-10min bouts of moderate intensity physical activity) may be too ambitious. To enable targeted exercise therapy to those most in need, I investigated the clinical predictors of low physical activity levels. Older age and the presence of refractory ascites were independent predictors of low physical activity, with the LFI being the most robust and clinically useful physical frailty measure to predict low physical activity. Intensity, rather than volume of physical activity was associated with lower physical frailty levels indicating a message of “when you move, move with intensity” may be most beneficial to patients with ESLD. Further research studies should focus on delivering short bursts of higher intensity activity within their exercise interventions to evaluate impact of physical activity on reducing physical frailty in ESLD

The experiences of young people with epidermolysis bullosa simplex: a qualitative study

Objective: To explore the experiences of young people with Epidermolysis Bullosa Simplex (EBS). Method: 11 participants aged 10 -14 years were interviewed. Interpretative Phenomenological Analysis was employed. Results: A key theme was ‘self as different’. This related to experiences of negative treatment and exclusion from peers; a lack of understanding of others about the condition; and a sense of the self as ‘wrong’. Conclusions: Findings indicate the importance of providing appropriate psychological and peer support, as well as wider community education and intervention, as part of the holistic treatment of young people with this chronic, painful and visible skin condition

Laying low: Rugged lowland rainforest preferred by feral cats in the Australian Wet Tropics

Invasive mesopredators are responsible for the decline of many species of native mammals worldwide. Feral cats have been causally linked to multiple extinctions of Australian mammals since European colonization. While feral cats are found throughout Australia, most research has been undertaken in arid habitats, thus there is a limited understanding of feral cat distribution, abundance, and ecology in Australian tropical rainforests. We carried out camera-trapping surveys at 108 locations across seven study sites, spanning 200 km in the Australian Wet Tropics. Single-species occupancy analysis was implemented to investigate how environmental factors influence feral cat distribution. Feral cats were detected at a rate of 5.09 photographs/100 days, 11 times higher than previously recorded in the Australian Wet Tropics. The main environmental factors influencing feral cat occupancy were a positive association with terrain ruggedness, a negative association with elevation, and a higher affinity for rainforest than eucalypt forest. These findings were consistent with other studies on feral cat ecology but differed from similar surveys in Australia. Increasingly harsh and consistently wet weather conditions at higher elevations, and improved shelter in topographically complex habitats may drive cat preference for lowland rainforest. Feral cats were positively associated with roads, supporting the theory that roads facilitate access and colonization of feral cats within more remote parts of the rainforest. Higher elevation rainforests with no roads could act as refugia for native prey species within the critical weight range. Regular monitoring of existing roads should be implemented to monitor feral cats, and new linear infrastructure should be limited to prevent encroachment into these areas. This is pertinent as climate change modeling suggests that habitats at higher elevations will become similar to lower elevations, potentially making the environment more suitable for feral cat populations

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

The ribosomal P-stalk couples amino acid starvation to GCN2 activation in mammalian cells

The eukaryotic translation initiation factor 2α (eIF2α) kinase GCN2 is activated by amino acid starvation to elicit a rectifying physiological program known as the Integrated Stress Response (ISR). A role for uncharged tRNAs as activating ligands of yeast GCN2 is supported experimentally. However, mouse GCN2 activation has recently been observed in circumstances associated with ribosome stalling with no global increase in uncharged tRNAs. We report on a mammalian CHO cell-based CRISPR-Cas9 mutagenesis screen for genes that contribute to ISR activation by amino acid starvation. Disruption of genes encoding components of the ribosome P-stalk, uL10 and P1, selectively attenuated GCN2-mediated ISR activation by amino acid starvation or interference with tRNA charging without affecting the endoplasmic reticulum unfolded protein stress-induced ISR, mediated by the related eIF2α kinase PERK. Wildtype ribosomes isolated from CHO cells, but not those with P-stalk lesions, stimulated GCN2-dependent eIF2α phosphorylation in vitro. These observations support a model whereby lack of a cognate charged tRNA exposes a latent capacity of the ribosome P-stalk to activate GCN2 in cells and help explain the emerging link between ribosome stalling and ISR activation

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

Biofouling resistant materials based on micro‐structured surfaces with liquid‐repellent properties

Adhesion of contaminants on various polymer-based devices during fluid-substrate interactions is a common problem that can cause biofouling andcorrosion. In this study, hierarchical structures with submicron features onpolypropylene (PP), high-density polyethylene (HDPE), and polycarbonate (PC)are fabricated by femtosecond laser ablation. The effect of the hierarchicalstructures on surface wettability, droplet impact, and bacterial attachment hasbeen examined. Our results demonstrate that the structured polymeric sub-strates facilitate large contact angles and minimal interfacial adhesion, allowingdroplets to roll off at a low angle of inclination below 5◦. Further, rendering thehierarchicalstructureswithalow-surface-energycoatingcanenablethesurfacesto exhibit superamphiphobic properties. The low interfacial adhesion properties,as accounted by the large contact angles and small contact angle hysteresis, ofsuch surfaces prevent bacterial attachment and biofilm formation. The findingsprovide a design principle for creating affordable biofouling resistant surfaceswith a submicron topography hat can be used for engineering and biomedical devices