miR-1343 attenuates pathways of fibrosis by targeting the TGF- receptors

Irreversible respiratory obstruction resulting from progressive airway damage, inflammation and fibrosis is a feature of several chronic respiratory diseases, including cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). The cytokine transforming growth factor β (TGF-β) has a pivotal role in promoting lung fibrosis and is implicated in respiratory disease severity. In the present study, we show that a previously uncharacterized miRNA, miR-1343, reduces the expression of both TGF-β receptor 1 and 2 by directly targeting their 3′-UTRs. After TGF-β exposure, elevated intracellular miR-1343 significantly decreases levels of activated TGF-β effector molecules, pSMAD2 (phosphorylated SMAD2) and pSMAD3 (phosphorylated SMAD3), when compared with a non-targeting control miRNA. As a result, the abundance of fibrotic markers is reduced, cell migration into a scratch wound impaired and epithelial-to-mesenchymal transition (EMT) repressed. Mature miR-1343 is readily detected in human neutrophils and HL-60 cells and is activated in response to stress in A549 lung epithelial cells. miR-1343 may have direct therapeutic applications in fibrotic lung disease

An eHealth Intervention for Patients in Rural Areas: Preliminary Findings From a Pilot Feasibility Study

This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Research Protocols, is properly cited. The complete bibliographic information, a link to the original publication on http://www.researchprotocols.org, as well as this copyright and license information must be included.Background: eHealth facilitation of chronic disease management has potential to increase engagement and effectiveness and extend access to care in rural areas. Objective: The objective of this study was to demonstrate the feasibility and acceptability of an eHealth system for the management of chronic conditions in a rural setting. Methods: We developed an online management program which incorporated content from the Flinders Chronic Condition Management Program (Flinders Program) and used an existing software platform (goACT), which is accessible by patients and health care workers using either Web-enabled mobile phone or Internet, enabling communication between patients and clinicians. We analyzed the impact of this eHealth system using qualitative and simple quantitative methods. Results: The eHealth system was piloted with 8 recently hospitalized patients from rural areas, average age 63 (SD 9) years, each with an average of 5 chronic conditions and high level of psychological distress with an average K10 score of 32.20 (SD 5.81). Study participants interacted with the eHealth system. The average number of logins to the eHealth system by the study participants was 26.4 (SD 23.5) over 29 weeks. The login activity was higher early in the week. Conclusions: The pilot demonstrated the feasibility of implementing and delivering a chronic disease management program using a Web-based patient-clinician application. A qualitative analysis revealed burden of illness and low levels of information technology literacy as barriers to patient engagement

Exploring the association between recent concussion, subconcussive impacts and depressive symptoms in male Australian Football players

Objectives: To explore the association between depressive symptoms and recent head-related trauma (diagnosed concussion, subconcussive impacts) in semiprofessional male Australian Football (AF) players. Methods: Sixty-nine semiprofessional male players from a West Australian Football League (WAFL) club participated in the study (M age =21.81, SD=2.91 years). Depressive symptoms were measured using the Centre for Epidemiological Studies Depression Scale. Injuries and potential confounding variables (eg, pre-existing mental health condition; alcohol or drug hangovers; experiencing a stressful event) were self-reported anonymously using the WAFL Injury Report Survey. Both tools were administered every 2-weeks over the first 22-weeks of the WAFL season. Controlling for potential confounding variables and other injuries, a repeated measures generalised estimating equations model assessed the risk of clinically relevant depressive symptoms occurring, when diagnosed concussion or subconcussive impacts were experienced. Results: A total of 10 concussions and 183 subconcussive impacts were reported. Players who experienced a concussion were almost nine times more likely to experience clinically relevant depressive symptoms (OR 8.88, 95% CI 2.65 to 29.77, p \u3c 0.001). Although elevated, depressive symptoms following subconcussive impacts were not statistically significant (OR 1.13, 95% CI 0.67 to 1.92, p = 0.641). Conclusion: These findings indicate that semiprofessional AF athletes may be at risk of experiencing depressive symptoms after concussion. Severity (concussion vs subconcussive impacts) and dose (number of impacts) appear to have an important relationship with depressive symptom outcomes in this cohort and should be considered for further research and management of player welfare. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ

“I\u27m making a positive change in my life”: A mixed method evaluation of a well-being tertiary education unit

Issue Addressed: Mental health disorders (MHDs) are prevalent amongst university students with detrimental impacts on individual students, universities and the wider community. There is an urgent need for proactive and preventative strategies to address the mental health crisis in the university population. This study evaluated the efficacy of a 13-week unit developed to directly educate university students about ways to improve and maintain well-being. Methods: Fifty-eight university students from five disciplines participated in a 13-week elective undergraduate unit “Well-Being Fundamentals for Success” as part of their degree. The Act Belong Commit mental health promotion campaign framework formed the basis of teaching materials. Outcome well-being measures were self-assessed at weeks 1, 6 and 12 using four scales: (1) Warwick-Edinburgh Mental Well-being Scale (WEMWBS); (2) Perceived Stress Scale (PSS); (3) Brief Resilience Scale (BRS) and (4) Mindful Attention Awareness Scale (MAAS). Post-unit group interviews (n = 11) were analysed for key themes. Results: Linear mixed models demonstrated a significant improvement in BRS over the semester; well-being (WEMBS) and mindful attention (MAAS) did increase but not significantly. There was a significant increase in stress (PSS) over the semester. Key themes that emerged from the group interviews were that (1) University life contributes to well-being; (2) University life contributes to stress; (3) The well-being unit helped students see and do things differently; (4) An overall endorsement of the unit. Conclusion: University students’ resilience increased over the semester following participation in a curriculum focused on well-being which featured a combination of theoretical content and experiential workshops. So what? Incorporating mental well-being curriculum into tertiary education is proactive preventive health strategy which may assist with the increasing prevalence of MHD in Australia

Comparison of various characteristics of women who do and do not attend for breast cancer screening

BACKGROUND: Information regarding the characteristics and health of women who do and do not attend for breast cancer screening is limited and representative data are difficult to obtain. METHODS: Information on age, deprivation and prescriptions for various medications was obtained for all women at two UK general practices who were invited to breast cancer screening through the National Health Service Breast Screening Programme. The characteristics of women who attended and did not attend screening were compared. RESULTS: Of the 1064 women invited to screening from the two practices, 882 (83%) attended screening. Screening attenders were of a similar age to non-attenders but came from significantly less deprived areas (30% of attenders versus 50% of non-attenders came from the most deprived areas, P < 0.0001) and were more likely to have a current prescription for hormone replacement therapy (32% versus 19%, P < 0.0001). No significant differences in recent prescriptions of medication for hypertension, heart disease, hypercholesterolaemia, diabetes mellitus, asthma, thyroid disease or depression/anxiety were observed between attenders and non-attenders. CONCLUSION: Women who attend the National Health Service Breast Screening Programme come from less deprived areas and are more likely to have a current prescription for hormone replacement therapy than non-attenders, but do not differ in terms of age or recent prescriptions for various other medications

Exploring patients’ experiences of analgesia after major lower limb amputation: A qualitative study

OBJECTIVES: To explore patient experiences, understanding and perceptions of analgesia following major lower limb amputation. DESIGN: Qualitative interview study, conducted as part of a randomised controlled feasibility trial. SETTING: Participants were recruited from two general hospitals in South Wales. PARTICIPANTS: Interview participants were patients enrolled in PLACEMENT (Perineural Local Anaesthetic Catheter aftEr Major lowEr limb amputatioN Trial): a randomised controlled feasibility trial comparing the use of perineural catheter (PNC) versus standard care for postoperative pain relief following major lower limb amputation. PLACEMENT participants who completed 5-day postoperative follow-up, were able and willing to participate in a face-to-face interview, and had consented to be contacted, were eligible to take part in the qualitative study. A total of 20 interviews were conducted with 14 participants: 10 male and 4 female. METHODS: Semi-structured, face-to-face interviews were conducted with participants over two time points: (1) up to 1 month and (2) at least 6 months following amputation. Interviews were audio-recorded, transcribed verbatim and analysed using a framework approach. RESULTS: Interviews revealed unanticipated benefits of PNC usage for postoperative pain relief. Participants valued the localised and continuous nature of this mode of analgesia in comparison to opioids. Concerns about opioid dependence and side effects of pain relief medication were raised by participants in both treatment groups, with some reporting trying to limit their intake of analgesics. CONCLUSIONS: Findings suggest routine placement of a PNC following major lower limb amputation could reduce postoperative pain, particularly for patient groups at risk of postoperative delirium. This method of analgesic delivery also has the potential to reduce preoperative anxiety, alleviate the burden of pain management and minimise opioid use. Future research could further examine the comparison between patient-controlled analgesia and continuous analgesia in relation to patient anxiety and satisfaction with pain management. TRIAL REGISTRATION NUMBER: ISRCTN: 85710690; EudraCT: 2016-003544-37

The Murray Darling Basin Plan is not delivering - there\u27s no more time to waste

More than five years after the Murray Darling Basin Plan was implemented, it\u27s clear that it is not delivering on its key objectives. The Basin Plan, at its core, is about reducing the amount of water that can be extracted from its streams, rivers and aquifers. It includes an environmental water strategy to improve the conditions of the wetlands and rivers of the basin. The Productivity Commission will conduct a five-yearly inquiry into the effectiveness of the Basin Plan in 2018. It is high time to explain what is really going on in the Basin and water recovery. For this reason we have all signed the Murray-Darling Basin Declaration to explain what has gone wrong, to call for a freeze on funding for new irrigation projects until the outcomes of water recovery has been fully and independently audited, and to call for the establishment of an independent, expert body to deliver on the key goals of the Water Act (2007)

PrEdiction of Risk and Communication of outcomE followIng major lower limb amputation – a collaboratiVE study (PERCEIVE): Protocol for the PERCEIVE qualitative study

INTRODUCTION: Deciding whether to proceed with a major lower limb amputation is life-changing and complex, and it is crucial that the right decision is made at the right time. However, medical specialists are known to poorly predict risk when assessing patients for major surgery, and there is little guidance and research regarding decisions about amputation. The process of shared decision-making between doctors and patients during surgical consultations is also little understood. Therefore, the aim of this study is to analyse in depth the communication, consent, risk prediction and decision-making process in relation to major lower limb amputation. METHODS AND ANALYSIS: Consultations between patients and surgeons at which major lower limb amputation is discussed will be audio-recorded for 10–15 patients. Semi-structured follow-up interviews with patients (and relatives/carers) will then be conducted at two time points: as soon as possible/appropriate after a decision has been reached regarding surgery, and approximately 6 months later. Semi-structured interviews will also be conducted with 10–15 healthcare professionals working in the UK National Health Service (NHS) involved in amputation decision-making. This will include surgeons, anaesthetists and specialist physiotherapists at 2–4 NHS Health Boards/Trusts in Wales and England. Discourse analysis will be used to analyse the recorded consultations; interviews will be analysed thematically. Finally, workshops will be held with patients and healthcare professionals to help synthesise and interpret findings. ETHICS AND DISSEMINATION: The study has been approved by Wales REC 7 (20/WA/0351). Study findings will be published in international peer-reviewed journal(s) and presented at national and international scientific meetings. Findings will also be disseminated to a wide NHS and lay audience via presentations at meetings and written summaries for key stakeholder groups

The PERCEIVE quantitative study: PrEdiction of Risk and Communication of outcome following major lower limb amputation: protocol for a collaboratiVE study

BACKGROUND: Accurate prediction of outcomes following surgery with high morbidity and mortality rates is essential for informed shared decision-making between patients and clinicians. It is unknown how accurately healthcare professionals predict outcomes following major lower-limb amputation (MLLA). Several MLLA outcome-prediction tools have been developed. These could be valuable in clinical practice, but most require validation in independent cohorts before routine clinical use can be recommended. The primary aim of this study is to evaluate the accuracy of healthcare professionals’ predictions of outcomes in adult patients undergoing MLLA for complications of chronic limb-threatening ischaemia (CLTI) or diabetes. Secondary aims include the validation of existing outcome-prediction tools. METHOD: This study is an international, multicentre prospective observational study including adult patients undergoing a primary MLLA for CLTI or diabetes. Healthcare professionals’ accuracy in predicting outcomes at 30-days (death, morbidity and MLLA revision) and 1-year (death, MLLA revision and ambulation) will be evaluated. Sixteen existing outcome-prediction tools specific to MLLA will be examined for validity. Data collection began on 1 October 2020; the end of follow-up will be 1 May 2022. The C-statistic, Hosmer–Lemeshow test, reclassification tables and Brier score will be used to evaluate the predictive performance of healthcare professionals and prediction tools, respectively. STUDY REGISTRATION AND DISSEMINATION: This study will be registered locally at each centre in accordance with local policies before commencing data collection, overseen by local clinician leads. Results will be disseminated to all centres, and any subsequent presentation(s) and/or publication(s) will follow a collaborative co-authorship model

Quantitative methods for the analysis of CFTR transcripts/splicing variants

AbstractIn cystic fibrosis (CF), transcript analysis and quantification are important for diagnosis, prognosis and also as surrogate markers for some therapies including gene therapy. Classical RNA-based methods require significant expression levels in target samples for appropriate analysis, thus PCR-based methods are evolving towards reliable quantification. Various protocols for the quantitative analysis of CFTR transcripts (including those resulting from splicing variants) are described and discussed here