‘It's like the bad guy in a movie who just doesn't die’ : a qualitative exploration of young people's adaptation to eczema and implications for self‐care

Background Eczema is a common childhood inflammatory skin condition, affecting more than one in five children. A popular perception is that children ‘outgrow eczema’, although epidemiological studies have shown that, for many, eczema follows a lifelong episodic course. Objectives To explore the perceptions of young people about the nature of their eczema and how these perceptions relate to their self‐care and adapting to living with eczema. Methods This is a secondary inductive thematic analysis of interviews conducted for Healthtalk.org. In total 23 interviews with young people with eczema were included. Of the 23 participants, 17 were female and six male, ranging from 17 to 25 years old. Results Participants generally experienced eczema as an episodic long‐term condition and reported a mismatch between information received about eczema and their experiences. The experience of eczema as long term and episodic had implications for self‐care, challenging the process of identifying triggers of eczema flare‐ups and evaluating the success of treatment regimens. Participants’ experiences of eczema over time also had implications for adaptation and finding a balance between accepting eczema as long term and hoping it would go away. This linked to a gradual shift in treatment expectations from ‘cure’ to ‘control’ of eczema. Conclusions For young people who continue to experience eczema beyond childhood, a greater focus on self‐care for a long‐term condition may be helpful. Greater awareness of the impact of early messages around ‘growing out of’ eczema and provision of high‐quality information may help patients to manage expectations and support adaptation to treatment regimens

Boundary spanning and identity work in the clinical research delivery workforce: a qualitative study of research nurses, midwives and allied health professionals in the National Health Service, United Kingdom.

BackgroundResearch nurses, midwives and allied health professionals are members of an important emergent profession delivering clinical research and, in the United Kingdom, have been the focus of considerable investment by the National Institute for Health Research (NIHR). This paper considers the experiences of research nurses, midwives and allied health professionals in relation to professional identity work, recognizing these are coproduced alongside others that they interact with (including patients, clinical staff and other research staff).MethodsSemi-structured interviews were conducted with 45 nurses, midwives and allied health professionals in the UK about their experiences of working in research delivery. Interviews were transcribed verbatim and thematically coded and analysed.ResultsOur analysis highlights how research nurses, midwives and allied health professionals adjust to new roles, shift their professional identities and undertake identity work using uniforms, name badges and job titles as they negotiate complex identities.ConclusionsResearch nurses, midwives and allied health professionals experience considerable challenges as they enter and transition to a research delivery role, with implications for their sense of professional identities. A change in the work that they undertake and how they are (or perceive they are) viewed by others (including clinical non-research colleagues and patients) has implications for their sense of professional and individual identity. The tensions involved extend to their views on symbols of professional identity, such as uniforms, and as they seek to articulate and demonstrate the value of their conjoined role in research and as a healthcare professional, within the unfolding landscape of health research. We embed our study findings in the context of the newly emerging clinical research practitioner workforce, which further exacerbates and complicates the role and identity complexity for nurses, midwives and allied health professionals in research delivery

Local Nodes in Global Networks: The Geography of Knowledge Flows in Biotechnology Innovation

The literature on innovation and interactive learning has tended to emphasize the importance of local networks, inter-firm collaboration and knowledge flows as the principal source of technological dynamism. More recently, however, this view has come to be challenged by other perspectives that argue for the importance of non-local knowledge flows. According to this alternative approach, truly dynamic economic regions are characterized both by dense local social interaction and knowledge circulation, as well as strong inter-regional and international connections to outside knowledge sources and partners. This paper offers an empirical examination of these issues by examining the geography of knowledge flows associated with innovation in biotechnology. We begin by reviewing the growing literature on the nature and geography of innovation in biotechnology research and the commercialization process. Then, focusing on the Canadian biotech industry, we examine the determinants of innovation (measured through patenting activity), paying particular attention to internal resources and capabilities of the firm, as well as local and global flows of knowledge and capital. Our study is based on the analysis of Statistics Canada’s 1999 Survey of Biotechnology Use and Development, which covers 358 core biotechnology firms. Our findings highlight the importance of in-house technological capability and absorptive capacity as determinants of successful innovation in biotechnology firms. Furthermore, our results document the precise ways in which knowledge circulates, in both embodied and disembodied forms, both locally and globally. We also highlight the role of formal intellectual property transactions (domestic and international) in promoting knowledge flows. Although we document the importance of global networks in our findings, our results also reveal the value of local networks and specific forms of embedding. Local relational linkages are especially important when raising capital—and the expertise that comes with it—to support innovation. Nevertheless, our empirical results raise some troubling questions about the alleged pre-eminence of the local in fostering innovation

The Large GTPase Dynamin Associates with the Spindle Midzone and Is Required for Cytokinesis

AbstractCytokinesis involves the concerted efforts of the microtubule and actin cytoskeletons as well as vesicle trafficking and membrane remodeling to form the cleavage furrow and complete daughter cell separation (for reviews, see [1–6]). The exact mechanisms that support membrane remodeling during cytokinesis remain largely undefined. In this study, we report that the large GTPase dynamin, a protein involved in membrane tubulation and vesiculation [7, 8], is essential for successful cytokinesis. Using biochemical and morphological methods, we demonstrate that dynamin localizes to the spindle midzone and the subsequent intercellular bridge in mammalian cells and is also enriched in spindle midbody extracts. In Caenorhabditis elegans, dynamin localized to newly formed cleavage furrow membranes and accumulated at the midbody of dividing embryos in a manner similar to dynamin localization in mammalian cells. Further, dynamin function appears necessary for cytokinesis, as C. elegans embryos from a dyn-1 ts strain [9], as well as dynamin RNAi-treated embryos, showed a marked defect in the late stages of cytokinesis. These findings indicate that, during mitosis, conventional dynamin is recruited to the spindle midzone and the subsequent intercellular bridge, where it plays an essential role in the final separation of dividing cells

Lipophagy and Alcohol-Induced Fatty Liver

This review describes the influence of ethanol consumption on hepatic lipophagy, a selective form of autophagy during which fat-storing organelles known as lipid droplets (LDs) are degraded in lysosomes. During classical autophagy, also known as macroautophagy, all forms of macromolecules and organelles are sequestered in autophagosomes, which, with their cargo, fuse with lysosomes, forming autolysosomes in which the cargo is degraded. It is well established that excessive drinking accelerates intrahepatic lipid biosynthesis, enhances uptake of fatty acids by the liver from the plasma and impairs hepatic secretion of lipoproteins. All the latter contribute to alcohol-induced fatty liver (steatosis). Here, our principal focus is on lipid catabolism, specifically the impact of excessive ethanol consumption on lipophagy, which significantly influences the pathogenesis alcohol-induced steatosis. We review findings, which demonstrate that chronic ethanol consumption retards lipophagy, thereby exacerbating steatosis. This is important for two reasons: (1) Unlike adipose tissue, the liver is considered a fat-burning, not a fat-storing organ. Thus, under normal conditions, lipophagy in hepatocytes actively prevents lipid droplet accumulation, thereby maintaining lipostasis; (2) Chronic alcohol consumption subverts this fat-burning function by slowing lipophagy while accelerating lipogenesis, both contributing to fatty liver. Steatosis was formerly regarded as a benign consequence of heavy drinking. It is now recognized as the first hit in the spectrum of alcohol-induced pathologies that, with continued drinking, progresses to more advanced liver disease, liver failure, and/or liver cancer. Complete lipid droplet breakdown requires that LDs be digested to release their high-energy cargo, consisting principally of cholesteryl esters and triacylglycerols (triglycerides). These subsequently undergo lipolysis, yielding free fatty acids that are oxidized in mitochondria to generate energy. Our review will describe recent findings on the role of lipophagy in LD catabolism, how continuous heavy alcohol consumption affects this process, and the putative mechanism(s) by which this occurs

Development of prognostic models for survival and care status in sporadic Creutzfeldt-Jakob disease

Sporadic Creutzfeldt-Jakob disease, the most common human prion disease, typically presents as a rapidly progressive dementia and has a highly variable prognosis. Despite this heterogeneity, clinicians need to give timely advice on likely prognosis and care needs. No prognostic models have been developed that predict survival or time to increased care status from the point of diagnosis. We aimed to develop clinically useful prognostic models with data from a large prospective observational cohort study. Five hundred and thirty-seven patients were visited by mobile teams of doctors and nurses from the National Health Service National Prion Clinic within 5 days of notification of a suspected diagnosis of sporadic Creutzfeldt-Jakob disease, enrolled to the study between October 2008 and March 2020, and followed up until November 2020. Prediction of survival over 10-, 30- and 100-day periods was the main outcome. Escalation of care status over the same time periods was a secondary outcome for a subsample of 113 patients with low care status at initial assessment. Two hundred and eighty (52.1%) patients were female and the median age was 67.2 (interquartile range 10.5) years. Median survival from initial assessment was 24 days (range 0-1633); 414 patients died within 100 days (77%). Ten variables were included in the final prediction models: sex; days since symptom onset; baseline care status; PRNP codon 129 genotype; Medical Research Council Prion Disease Rating Scale, Motor and Cognitive Examination Scales; count of MRI abnormalities; Mini-Mental State Examination score and categorical disease phenotype. The strongest predictor was PRNP codon 129 genotype (odds ratio 6.65 for methionine homozygous compared with methionine-valine heterozygous; 95% confidence interval 3.02-14.68 for 30-day mortality). Of 113 patients with lower care status at initial assessment, 88 (78%) had escalated care status within 100 days, with a median of 35 days. Area under the curve for models predicting outcomes within 10, 30 and 100 days was 0.94, 0.92 and 0.91 for survival, and 0.87, 0.87 and 0.95 for care status escalation, respectively. Models without PRNP codon 129 genotype, which is not immediately available at initial assessment, were also highly accurate. We have developed a model that can accurately predict survival and care status escalation in sporadic Creutzfeldt-Jakob disease patients using clinical, imaging and genetic data routinely available in a specialist national referral service. The utility and generalizability of these models to other settings could be prospectively evaluated when recruiting to clinical trials and providing clinical care

Lipid droplet membrane proteome remodeling parallels ethanol-induced hepatic steatosis and its resolution

Abstract Lipid droplets (LDs) are composed of neutral lipids enclosed in a phospholipid monolayer, which harbors membrane-associated proteins that regulate LD functions. Despite the crucial role of LDs in lipid metabolism, remodeling of LD protein composition in disease contexts, such as steatosis, remains poorly understood. We hypothesized that chronic ethanol consumption, subsequent abstinence from ethanol, or fasting differentially affects the LD membrane proteome content and that these changes influence how LDs interact with other intracellular organelles. Here, male Wistar rats were pair-fed liquid control or ethanol diets for 6 weeks, and then, randomly chosen animals from both groups were either refed a control diet for 7 days or fasted for 48 h before euthanizing. From all groups, LD membrane proteins from purified liver LDs were analyzed immunochemically and by MS proteomics. Liver LD numbers and sizes were greater in ethanolfed rats than in pair-fed control, 7-day refed, or fasted rats. Compared with control rats, ethanol feeding markedly altered the LD membrane proteome, enriching LD structural perilipins and proteins involved in lipid biosynthesis, while lowering LD lipase levels. Ethanol feeding also lowered LDassociated mitochondrial and lysosomal proteins. In 7-day refed (i.e., ethanol-abstained) or fasted-ethanolfed rats, we detected distinct remodeling of the LD proteome, as judged by lower levels of lipid biosynthetic proteins, and enhanced LD interaction with mitochondria and lysosomes. Our study reveals evidence of significant remodeling of the LD membrane proteome that regulates ethanol-induced steatosis, its resolution after withdrawal and abstinence, and changes in LD interactions with other intracellular organelles