Prevalence, patterns, and predictors of patient-reported non-motor outcomes at 30 days after acute stroke: prospective observational hospital cohort study

Background: Adverse non-motor outcomes are common after acute stroke and likely to substantially affect quality of life, yet few studies have comprehensively assessed their prevalence, patterns, and predictors across multiple health domains.// Aims: We aim to identify the prevalence, patterns and the factors associated with non-motor outcomes 30 days after stroke.// Methods: This prospective observational hospital cohort study (Stroke Investigation in North and Central London (SIGNAL) identified patients with acute ischaemic stroke or intracerebral haemorrhage (ICH) admitted to the Hyperacute Stroke Unit (HASU) University College Hospital (UCH), London, between August 1st 2018 and August 31st 2019. We assessed non-motor outcomes (anxiety, depression, fatigue, sleep, participation in social roles and activities, pain, bowel, and bladder function) at 30-day follow-up using the Patient Reported Outcome Measurement Information System-Version 29 (PROMIS-29) scale and Barthel Index scale.// Results: We obtained follow-up data for 605/719 (84.1%) eligible patients (mean age 72.0 years; 48.3% female; 521 with ischaemic stroke, 84 with ICH). Anxiety (57.0%), fatigue (52.7%), bladder dysfunction (50.2%), reduced social participation (49.2%), and pain (47.9%) were the commonest adverse non-motor outcomes. The rates of adverse non-motor outcomes in ≥1, ≥2 and ≥3 domains were 89%, 66.3% and 45.8%, respectively; in adjusted analyses, stroke due to ICH (compared to ischaemic stroke) and admission stroke severity were the strongest and most consistent predictors. There were significant correlations between; bowel dysfunction and bladder dysfunction (κ= 0.908); reduced social participation and bladder dysfunction (κ= 0.844); and anxiety and fatigue (κ= 0.613). We did not identify correlation for other pairs of non-motor domains.// Conclusions: Adverse non-motor outcomes are very common at one month after stroke, affecting nearly 90% of evaluated patients in at least one health domain, about two-thirds in two or more domains, and almost 50% in three or more domains. Stroke due to ICH and admission stroke severity were the strongest and most consistent predictors. Adverse outcomes occur in pairs of domains such as with anxiety and fatigue.Our findings emphasise the importance of a multi-domain approach to effectively identify adverse non-motor outcomes after stroke to inform the development of more holistic patient recovery programs

Glycosaminoglycan and Proteoglycan Biotherapeutics in Articular Cartilage Protection and Repair Strategies: Novel Approaches to Visco?supplementation in Orthobiologics

The aim of this study is to review developments in glycosaminoglycan and proteoglycan research relevant to cartilage repair biology and in particular the treatment of osteoarthritis (OA). Glycosaminoglycans decorate a diverse range of extracellular matrix and cell associated proteoglycans conveying structural organization and physico‐chemical properties to tissues. They play key roles mediating cellular interactions with bioactive growth factors, cytokines, and morphogenetic proteins, and structural fibrillar collagens, cell interactive and extracellular matrix proteoglycans, and glycoproteins which define tissue function. Proteoglycan degradation detrimentally affects tissue functional properties. Therapeutic strategies have been developed to counter these degenerative changes. Neo‐proteoglycans prepared from chondroitin sulfate or hyaluronan and hyaluronan or collagen‐binding peptides emulate the interactive, water imbibing, weight bearing, and surface lubricative properties of native proteoglycans. Many neo‐proteoglycans outperform native proteoglycans in terms of water imbibition, matrix stabilization, and resistance to proteolytic degradation. The biospecificity of recombinant proteoglycans however, provides precise attachment to native target molecules. Visco‐supplements augmented with growth factors/therapeutic cells, hyaluronan, and lubricin (orthobiologicals) have the capacity to lubricate and protect cartilage, control inflammation, and promote cartilage repair and regeneration of early cartilage lesions and may represent a more effective therapeutic approach to the treatment of mild to moderate OA and deserve further study

The Mechanism of Ubiquitination in the Cullin-RING E3 Ligase Machinery: Conformational Control of Substrate Orientation

In cullin-RING E3 ubiquitin ligases, substrate binding proteins, such as VHL-box, SOCS-box or the F-box proteins, recruit substrates for ubiquitination, accurately positioning and orienting the substrates for ubiquitin transfer. Yet, how the E3 machinery precisely positions the substrate is unknown. Here, we simulated nine substrate binding proteins: Skp2, Fbw7, β-TrCP1, Cdc4, Fbs1, TIR1, pVHL, SOCS2, and SOCS4, in the unbound form and bound to Skp1, ASK1 or Elongin C. All nine proteins have two domains: one binds to the substrate; the other to E3 ligase modules Skp1/ASK1/Elongin C. We discovered that in all cases the flexible inter-domain linker serves as a hinge, rotating the substrate binding domain, optimally and accurately positioning it for ubiquitin transfer. We observed a conserved proline in the linker of all nine proteins. In all cases, the prolines pucker substantially and the pucker is associated with the backbone rotation toward the E2/ubiquitin. We further observed that the linker flexibility could be regulated allosterically by binding events associated with either domain. We conclude that the flexible linker in the substrate binding proteins orients the substrate for the ubiquitin transfer. Our findings provide a mechanism for ubiquitination and polyubiquitination, illustrating that these processes are under conformational control

AgBase: supporting functional modeling in agricultural organisms

AgBase (http://www.agbase.msstate.edu/) provides resources to facilitate modeling of functional genomics data and structural and functional annotation of agriculturally important animal, plant, microbe and parasite genomes. The website is redesigned to improve accessibility and ease of use, including improved search capabilities. Expanded capabilities include new dedicated pages for horse, cat, dog, cotton, rice and soybean. We currently provide 590 240 Gene Ontology (GO) annotations to 105 454 gene products in 64 different species, including GO annotations linked to transcripts represented on agricultural microarrays. For many of these arrays, this provides the only functional annotation available. GO annotations are available for download and we provide comprehensive, species-specific GO annotation files for 18 different organisms. The tools available at AgBase have been expanded and several existing tools improved based upon user feedback. One of seven new tools available at AgBase, GOModeler, supports hypothesis testing from functional genomics data. We host several associated databases and provide genome browsers for three agricultural pathogens. Moreover, we provide comprehensive training resources (including worked examples and tutorials) via links to Educational Resources at the AgBase website

Investigating Unsafe Behaviours in Traffic Conflict Situations: An Observational Study in Nigeria

Although road users are aware of the possible risks of engaging in unsafe behaviours while driving, they continue to do so. These behaviours often contribute to traffic incidents and crashes involving them and other road users. This study set out to analyse the effect of road user type, location and time of day on unsafe driving behaviours observed in traffic conflict situations. Data were collected by road side observation at three different locations in the eastern part of Nigeria using the traffic conflict technique (TCT). This approach was adopted to overcome the inherent problems associated with reliable, inadequate and accessible crash data in Nigeria. In total 946 traffic conflicts were observed and statistical testing showed that drivers were involved in one or more unsafe behaviours prior to these conflicts. Of all unsafe behaviours observed, the incorrect use of indicators (13.3%) and tailgating (11.3%) were found to be the most prevalent, while road user type, location and time of day were found to be statistically associated with passenger scouting and other unsafe behaviours. Tricycle drivers were significantly more likely to engage in unsafe behaviours than vehicle drivers. Drivers are also more likely to engage in unsafe behaviours on straight roads. Additionally, a greater number of these unsafe behaviours were observed during the peak periods. It is recommended that better road infrastructure, more effective regulations and enforcement, and proper road safety education could help improve traffic safety in Nigeria

Knowledge, energy sustainability, and vulnerability in the demographics of smart home technology diffusion

In this empirical study, we explore the user acceptance of smart home technologies by asking: How do people perceive their opportunities and drawbacks? What factors shape their perceptions? What implications does this have for future energy savings, sustainability, and policy? Based on a mixed methods approach involving three focus groups (N = 18) and a nationally representative survey of adults (N = 1032) in the United Kingdom, we explore the demographics, preferences, and risks of smart home technology. We do this via the lenses of knowledge and adoption; energy and climate sustainability; and vulnerability and exclusion. We explore how different classes of people—adopters versus non-adopters, high-income versus low-income, women and men, old versus young—support or oppose smart home technologies, have different degrees of knowledge and misperceptions, and reveal very different perceptions about the practices enabled by smart homes. In doing so, we show at times compelling links between smart homes and energy consumption, and possible negative impacts to poverty, inclusion, and empowerment