Keratin 15 (K15) is a type I keratin without a defined type II partner whose expression in epidermal diseases has not been investigated. In this study we have used LHK15, a monoclonal antibody raised against the last 17 amino acids of the K15 polypeptide, to show that K15 is expressed primarily in the basal keratinocytes of stratified tissues, including the fetal epidermis and fetal nail. Although K15 in normal hair follicles was virtually absent from hair bulbs, it was expressed by a subset of keratinocytes in the outer root sheath. By comparison, K14 expression was found throughout the outer root sheath of hair follicles; however, when both K14 alleles were naturally ablated, the expression of K15 was also observed throughout the outer root sheath of the follicles. Expression of K15 mRNA was assessed by in situ hybridization and corroborated the data from immunostaining. An increase in K15 mRNA and protein expression in hair follicles from the K14 ablated epidermis suggested an upregulation of the K15 gene in the absence of the K14 protein. In organotypical cultures where differentiating keratinocytes expressed markers of activated phenotype, i.e., K6 and K16, expression of K15 was undetectable. The expression of K15 mRNA and protein was also downregulated in two hyperproliferating situations, psoriasis and hypertrophic scars. Because keratinocytes in psoriasis and hypertrophic scars are activated, we conclude that K15 expression is not compatible with keratinocyte activation and the K15 gene is downregulated to maintain the activated phenotype.
This is a repository copy of Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH) : a stepped-wedge cluster-randomised trial. Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH) : a stepped-wedge cluster-randomised trial. The Lancet. ISSN 0140-6736 https://doi.org/10.1016/S0140-6736(18)32521-2 eprints@whiterose.ac.uk https://eprints.whiterose.ac.uk/ ReuseThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs (CC BY-NC-ND) licence. This licence only allows you to download this work and share it with others as long as you credit the authors, but you can't change the article in any way or use it commercially. More information and the full terms of the licence here: https://creativecommons.org/licenses/ Implications of all the available evidenceDespite the success of some smaller projects, there was no survival benefit from a national quality improvement programme to implement a care pathway for patients undergoing emergency abdominal surgery. To succeed, large national quality improvement programmes need to allow for differences between hospitals and ensure teams have both the time and resources needed to improve patient care.
Faecal immunochemical testing (FIT) has a high sensitivity for the detection of colorectal cancer (CRC). In a symptomatic population FIT may identify those patients who require colorectal investigation with the highest priority. FIT offers considerable advantages over the use of symptoms alone, as an objective measure of risk with a vastly superior positive predictive value for CRC, while conversely identifying a truly low risk cohort of patients. The aim of this guideline was to provide a clear strategy for the use of FIT in the diagnostic pathway of people with signs or symptoms of a suspected diagnosis of CRC. The guideline was jointly developed by the Association of Coloproctology of Great Britain and Ireland/British Society of Gastroenterology, specifically by a 21-member multidisciplinary guideline development group (GDG). A systematic review of 13 535 publications was undertaken to develop 23 evidence and expert opinion-based recommendations for the triage of people with symptoms of a suspected CRC diagnosis in primary care. In order to achieve consensus among a broad group of key stakeholders, we completed an extended Delphi of the GDG, and also 61 other individuals across the UK and Ireland, including by members of the public, charities and primary and secondary care. Seventeen research recommendations were also prioritised to inform clinical management.
IntroductionPositive health behaviours such as regular physical activity and a healthy diet have significant effects on cancer outcomes. There is a need for simple but effective behaviour change interventions with the potential to be implemented within the cancer care pathway. Habit-based advice encourages repetition of a behaviour in a consistent context so that the behaviour becomes increasingly automatic in response to a specific contextual cue. This approach therefore encourages long-term behaviour change and can be delivered through printed materials. ‘Healthy Habits for Life’ is a brief intervention based on habit theory, and incorporating printed materials plus a personally tailored discussion, that has been designed specifically for patients with a diagnosis of cancer. The aim of this trial was to test the effect of ‘Healthy Habits for Life’ on a composite health behaviour risk index (CHBRI) over 3 months in patients with a diagnosis of breast, colorectal or prostate cancer.Method and analysisA 2-arm, individually randomised controlled trial in patients with breast, colorectal and prostate cancer. Patients will be recruited over 18 months from 7 National Health Service Trusts in London and Essex. Following baseline assessments and allocation to intervention or usual care, patients are followed up at 3 and 6 months. The primary outcome will be change in CHBRI at 3 months. Maintenance of any changes over 6 months, and changes in individual health behaviours (including dietary intake, physical activity, alcohol consumption and smoking status) will also be explored.Ethics and disseminationEthical approval was obtained through the National Research Ethics Service Committee South Central—Oxford B via the Integrated Research Application System (reference number 14/SC/1369). Results of this study will be disseminated through peer-reviewed publications and scientific presentations.Trial registration number17421871.
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