NET4 and RabG3 link actin to the tonoplast and facilitate cytoskeletal remodelling during stomatal immunity.

Members of the NETWORKED (NET) family are involved in actin-membrane interactions. Here we show that two members of the NET family, NET4A and NET4B, are essential for normal guard cell actin reorganization, which is a process critical for stomatal closure in plant immunity. NET4 proteins interact with F-actin and with members of the Rab7 GTPase RABG3 family through two distinct domains, allowing for simultaneous localization to actin filaments and the tonoplast. NET4 proteins interact with GTP-bound, active RABG3 members, suggesting their function being downstream effectors. We also show that RABG3b is critical for stomatal closure induced by microbial patterns. Taken together, we conclude that the actin cytoskeletal remodelling during stomatal closure involves a molecular link between actin filaments and the tonoplast, which is mediated by the NET4-RABG3b interaction. We propose that stomatal closure to microbial patterns involves the coordinated action of immune-triggered osmotic changes and actin cytoskeletal remodelling likely driving compact vacuolar morphologies.

Association of Clostridioides difficile infection rates with social determinants of health in Denver area census tracts, 2016-2019.

We evaluated the association between census tract measures of socioeconomic status and Clostridioides difficile infection (CDI) rates in the Denver metro area from 2016 to 2019. Social vulnerability index, poverty, and race were associated with CDI. Findings may relate to differences in chronic disease prevalence, antibiotic exposure, and access to quality care.

Role dimensions of general practice nurses in Ireland.

INTRODUCTION: Primary care has the potential to address the challenges associated with the rise of chronic conditions and an aging population; however, General Practitioners are increasingly struggling to meet these demands. Fundamental to the provision of high-quality primary care is the role of the general practice nurse, who typically provides a wide range of services. Examining the current role of general practice nurses must be a first step to determining their educational needs for enhancing their long-term future contribution to primary care. METHOD: A survey design was used to explore the role of general practice nurses. A purposeful sample of general practice nurses (n=40) was undertaken between April and June 2019. Data were analysed using the Statistical Package for Social Science (SPSS V 25.0. Armonk, NY: IBM). RESULTS: General practice nurses appear to have an agenda in relation to activities associated with wound care, immunizations, and respiratory and cardiovascular issues. Challenges to future enhancement of the role were associated with undertaking further training and their experience of having more work transferred to general practice without concomitant reallocation of resources. DISCUSSION: General practice nurses have extensive clinical experience to deliver major improvements in primary care. Educational opportunities need to be provided for upskilling existing general practice nurses and to attract future nurses into this important area. Greater understanding of the role and the potential contribution of the role in general practice is required among medical colleagues and the public.

Operationalising a modified Delphi study to progress quality care process nursing metrics for acute care.

Background: Despite representing the largest occupational group within the healthcare workforce, evidence suggests that due to the complexity of nursing practice, nurses' contribution remains 'invisible'. Quality Care Metrics aligned to standards can offer valuable numerical information that quantify input, output and dimensions of nursing care processes in complex clinical and interprofessional milieus. Aims and objectives: Progress an evidence-based metric system to measure the quality and clinical safety of nursing care within acute care in Ireland. The objectives were to: classify quality care process nursing metrics and corresponding indicators pertinent to acute care; reach agreement on a selected set of robust metrics and corresponding indicators; and implement the findings of the study. Design: A modified four-round Delphi study. Methods: The modified Delphi study integrated a four-round survey of 422 nurses, face-to-face meetings with a patient representative and key stakeholders within acute services with a final consensus meeting inclusive of a panel of 26 expert nurse clinicians. Results: There was consensus on 11 quality care process nursing metrics and 53 corresponding indicators for the acute care setting. Despite the rating of 'critical' in the Delphi rounds, a concern was reported by participants on the subjective nature of three of the developed metrics: 'patient experience', 'patient engagement' and 'professional and ethical approach to care' based on the absence of objective measurement tools that include patient input. Conversely, this led to the conundrum for the panel of experts at the final consensus meeting who were divided in their views on objectively observing, recording and subsequent auditing of those three developed metrics in real-time clinical practice. Conclusion: This paper describes the operationalisation of a modified Delphi technique that progressed a set of 11 quality care process metrics and 53 corresponding indicators. The challenge now is the implementation of these quality care process metrics so that nurses' contribution to patient-centred care is tangible in acute care.

Potential for Paramedic roles in Irish General Practice: A qualitative study of stakeholder's perspectives.

Background: Irish health policy emphasises the role of Primary Care and General Practice however, there is a growing shortage of General Practitioners (GPs) in Ireland. Paramedics have traditionally focused on emergency care in the community. More recently Paramedics have taken on roles in General Practice in international jurisdictions, but not yet in Ireland. This study aimed to explore key stakeholder perceptions of 'the potential for Paramedic roles in Irish General Practice'. Methods: We conducted an exploratory, qualitative stakeholder consultation study incorporating in-depth semi structured telephone interviews followed by thematic analysis. Interviews were conducted with a total of eighteen participants that included six senior Paramedics (Advanced Paramedics), seven General Practitioners (GPs), three Practice Nurses and two Practice Managers. Results: Participants in this study expressed polarised views on the potential for Paramedic roles in Irish General Practice. Paramedics were enthusiastic, highlighting opportunity for professional development and favourable working conditions. GPs, Practice Nurses and Managers were more circumspect and had concerns that Paramedic scope and skillset was not currently aligned to General Practice care. GPs, Practice Nurses and Managers emphasised a greater role for expanded General Practice Nursing. There were varied perceptions on what the potential role of a Paramedic in General Practice might entail, but consensus that Government support would be required to facilitate any potential developments. Conclusions: The findings of this research can inform future development of novel roles in Irish General Practice and suggests that there is appetite from within the Paramedic profession to pursue such roles. A pilot demonstration project, grounded in an action research framework could address data gaps and potential concerns. Any future developments should occur in tandem with and with due consideration for the expansion of General Practice Nursing in Ireland.

Promoting nurse-led behaviour change interventions to prevent cardiovascular disease in disadvantaged communities: A scoping review.

Cardiovascular diseases (CVD) are the leading cause of death worldwide and they disproportionally affect people living in disadvantaged communities. Nurse-led behaviour change interventions have shown great promise in preventing CVD. However, knowledge regarding the impact and nature of such interventions in disadvantaged communities is limited. This review aimed to address this knowledge gap. A six-stage scoping review framework developed by Arksey and O'Malley, with revisions by Levac et al., was used. The search process was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Extension for Scoping Reviews (PRISMA-ScR). Three electronic databases were searched (PUBMED/MEDLINE, CINAHL Plus, and Cochrane CENTRAL), and included studies were analysed using Braun and Clarke's 'Thematic Analysis' approach. Initial searches yielded 952 papers and 30 studies were included in the review following duplicate, title/abstract, and full-text screening. The included studies indicate that nurse-led behaviour change primary prevention interventions in disadvantaged areas are largely effective; albeit the considerable variety of intervention approaches, study populations and outcome measures used to date make it difficult to ascertain this. Other identified key areas in the promotion of nurse-led behaviour change included tailoring interventions to specific populations, providing adequate training for nurses, overcoming patient access difficulties and encouraging patient engagement. Overall, the findings indicate that nurse-led behaviour change interventions for high-risk CVD patients in disadvantaged areas show much promise, although there is considerable variety in the interventions employed and studied to date. Further research is needed to examine the unique barriers and facilitators of interventions for specific disadvantaged groups.

Quality care process metrics for nurses working in general practice, mapping the evidence: a scoping review protocol.

Background: Irish general practice nursing roles have developed and grown exponentially in response to changing policy, clinical and workforce demands over the past three decades. However, as nursing care in general practice advances at pace, comprehensive evaluation of the general practice nurse (GPN) role has not been undertaken. Therefore, processes which enable robust data collection to carefully assess the role and facilitate development of services are required. Nursing quality care metrics (QCM) are an established mechanism which measure nursing care process, evaluate quality, and impact of care, and inform service development. The use of nursing QCM has been adopted within seven distinct healthcare settings in Ireland but not general practice. This scoping review is the first stage of a project which aims to inform development of QCM within Irish GPN settings. Aim: To explore and map the literature regarding the use, application, and impact of nursing quality care metrics within a general practice, primary care setting. Methods: The following five-stage methodological framework for scoping reviews proposed by Arksey and O'Malley will be used: (1) identifying the research question, (2) identifying relevant studies, (3) study selection, (4) charting/mapping the data and (5) collating, summarizing, and reporting results. The review will be conducted and reported in accordance with the PRISMA Extension for Scoping Reviews (PRISMA-ScR). Conclusions: The focus of this scoping review relates to QCM which specifically measure the work of general practice nurses. It is envisioned that synthesis of international literature will give a broad perspective about QCM, their use in general practice or primary care settings, and enrich understanding of their development. It is anticipated that findings will provide key information to policy makers and health professionals interested in planning, strengthening, and delivering  primary care in Ireland.

Role dimensions of practice nurses and interest in introducing advanced nurse practitioners in general practice in Ireland.

Background: Internationally many countries have implemented strategies to enhance primary care, to strengthen their health systems to cope with an aging population, the rise of chronic conditions, and increased costs. Primary care has the potential to address these challenges, however, general practitioners are increasingly struggling to meet patient demand resulting from a growing and aging population. Expanding the role of general practice nurses to advanced nurse practitioner (ANP) level has worked internationally and could equally be a solution to the Irish context. However, their current role must first be established as well as their level of interest in becoming an ANP. Aim: To explore the role of general practice nurses and their interest in becoming an ANP. Design: A survey design. Method: A purposeful sample of general practice nurses (n = 40) was undertaken between April and June 2019. Data were analyzed using the Statistical Package for Social Science (SPSS V 25.0; IBM). Results: General practice nurses appear to have an agenda in relation to activities associated with wound care, immunizations, respiratory and cardiovascular issues. Just over half of the respondents were not interested in becoming an ANP. Their perceived challenges associated with the implementation of the role include a lack of support from general practitioners, a lack of resources, insurance issues, and a lack of understanding of the role. Challenges were associated with undertaking further training and their experience of having more work transferred to general practice without concomitant reallocation of resources. Conclusion: General practice nurses have extensive clinical experience to deliver major improvements in primary care. Educational opportunities need to be provided for upskilling existing general practice nurses to advanced practice level. Greater understanding of the role and the potential contribution of the role in general practice is required among medical colleagues and the public.

Implications of a diagnosis of atypical small acinar proliferation (ASAP) and high-grade prostatic intraepithelial neoplasia (HGPIN) on prostate biopsy: a 5-year follow-up study.

BACKGROUND: In the era of active surveillance of low- and intermediate-risk prostatic cancer, a reconsideration of the implications of a biopsy report of ASAP and/or HGPIN may be timely. AIMS: We investigated the implications of a diagnosis of atypical small acinar proliferation (ASAP) and high-grade prostatic intraepithelial neoplasia (HGPIN) on prostate biopsy. METHODS: The rate of re-biopsy and the incidence of carcinoma on repeat biopsy for benign, HGPIN, and ASAP groups were compared. Mean PSA and PSA velocity was also compared between groups. RESULTS: There was an increased risk of developing prostate cancer in the following 5 years with a biopsy diagnosis of ASAP compared to benign (20% vs 5.9%, p = 0.009), and with a biopsy of HGPIN compared with benign (14.8% vs 5.9%, p = 0.005). The frequency of repeat biopsy following a diagnosis of ASAP (54.2%) vs. HGPIN (37%) was not significantly different (p = 0.079). The risk of developing prostate cancer was highest following a biopsy with concomitant ASAP and HGPIN compared to benign (50% vs 5.9%, p < 0.001). There was no significant difference in PSA values between the 3 diagnostic groups at the time of initial biopsy (p = 0.206). CONCLUSION: The findings of this study suggest that a biopsy diagnosis of ASAP ± HGPIN, on either initial or surveillance biopsy, provides support for earlier repeat mpMRI and/or re-biopsy. This may assist in directing to early re-biopsy those patients likely to have intermediate- and high-risk prostate cancer.

A Rapid Realist Review of Quality Care Process Metrics Implementation in Nursing and Midwifery Practice.

Quality measurement initiatives promote quality improvement in healthcare but can be challenging to implement effectively. This paper presents a Rapid Realist Review (RRR) of published literature on Quality Care-Process Metrics (QCP-M) implementation in nursing and midwifery practice. An RRR informed by RAMESES II standards was conducted as an efficient means to synthesize evidence using an expert panel. The review involved research question development, quality appraisal, data extraction, and evidence synthesis. Six program theories summarised below identify the key characteristics that promote positive outcomes in QCP-M implementation. Program Theory 1: Focuses on the evidence base and accessibility of the QCP-M and their ease of use by nurses and midwives working in busy and complex care environments. Program Theory 2: Examines the influence of external factors on QCP-M implementation. Program Theory 3: Relates to existing cultures and systems within clinical sites. Program Theory 4: Relates to nurses' and midwives' knowledge and beliefs. Program Theory 5: Builds on the staff theme of Programme Theory four, extending the culture of organizational learning, and highlights the meaningful engagement of nurses and midwives in the implementation process as a key characteristic of success. Program Theory 6: Relates to patient needs. The results provide nursing and midwifery policymakers and professionals with evidence-based program theory that can be translated into action-orientated strategies to help guide successful QCP-M implementation.

Informal preparation and years of experience: Key correlates of dyslexia knowledge among Massachusetts early elementary teachers.

BACKGROUND: Dyslexia is a neurobiological condition affecting phonological processing and characterized by reading and phonological awareness difficulties. We assessed correlations between dyslexia knowledge and five independent variables among early elementary teachers in Massachusetts. METHODS: We designed a survey based on two published assessment tools and surveyed 92 early elementary teachers. Using univariate and multivariate linear regression models, we assessed the relationships among knowledge (dependent variable) and confidence, feelings of preparedness, years of teaching experience, informal education and professional development opportunities (independent variables). RESULTS: The mean knowledge score was 68 ± 14%; teachers performed best on questions about perceptions of dyslexia, classroom management/teaching strategies and some dyslexia characteristics. Informal education and years of teaching experience were consistently positively associated with knowledge. DISCUSSION AND CONCLUSIONS: Formal training and professional development opportunities may need to focus more specifically on learning disabilities and dyslexia. Teachers should also have input on professional development needs. Our findings suggest a need for additional studies on strategies to improve educator knowledge of dyslexia and assess outcomes.

A case of adrenal Cushing's syndrome and primary hyperparathyroidism due to an atypical parathyroid adenoma.

Cushing's syndrome is a rare disorder of cortisol excess and is associated with significant morbidity and mortality. Hypercalcaemia due to hyperparathyroidism is a common condition; however, in 10% of young patients, it is associated with other endocrinopathies and occurs due to a genetic variant [e.g. multiple endocrine neoplasia (MEN) type 1 (MEN1), MEN2 or MEN4]. We report the case of a 31-year-old woman who was referred to the endocrinology out-patient service with an 8-month history of hirsutism, amenorrhoea and weight gain. Her biochemical work up was significant for adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome. Radiological investigations revealed an adrenal adenoma. During investigation she was also found to have primary hyperparathyroidism due to a parathyroid adenoma. Pre-operatively, the patient was commenced on metyrapone and both her adrenal and parathyroid lesions were resected successfully. There were several concerning findings on initial examination of the parathyroid tumour, including possible extension of the tumour through the capsule and vascular invasion; however, following extensive review, it was ultimately defined as an adenoma. Given the unusual presence of two endocrinopathies in a young patient, she subsequently underwent genetic testing. Analysis of multiple genes did not reveal any pathogenic variants. The patient is currently clinically well, with a normal adjusted calcium and no clinical features of cortisol excess. She will require long-term follow up for recurrence of both hypercalcaemia and hypercortisolaemia.

Application of action research in the field of healthcare: a scoping review protocol.

Background: Traditional research approaches are increasingly challenged in healthcare contexts as they produce abstract thinking rather than practical application. In this regard, action research is a growing area of popularity and interest, essentially because of its dual focus on theory and action. However, there is a need for action researchers not only to justify their research approach but also to demonstrate the quality of their empirical studies. Therefore, the authors set out to examine the current status of the quality of extant action research studies in healthcare to encourage improved scholarship in this area. The aim of this scoping review is to identify, explore and map the literature regarding the application of action research in either individual, group or organisational domains in any healthcare context. Methods: The systematic scoping review will search the literature within the databases of CINAHL, PubMed and ABI/Inform within the recent five-year period to investigate the scientific evidence of the quality of action research studies in healthcare contexts. The review will be guided by Arksey and O'Malley's five mandatory steps, which have been updated and published online by the Joanna Briggs Institute. The review will follow the PRISMA-ScR framework guidelines to ensure the standard of the methodological and reporting approaches are exemplary. Conclusion: This paper outlines the protocol for an exploratory scoping review to systematically and comprehensively map out the evidence as to whether action research studies demonstrate explicitly how the essential factors of a comprehensive framework of action research are upheld. The review will summarise the evidence on the quality of current action research studies in healthcare. It is anticipated that the findings will inform future action researchers in designing studies to ensure the quality of the studies is upheld.

Design, Synthesis and Characterization of HIV-1 CA-Targeting Small Molecules: Conformational Restriction of PF74.

Small molecules targeting the PF74 binding site of the HIV-1 capsid protein (CA) confer potent and mechanistically unique antiviral activities. Structural modifications of PF74 could further the understanding of ligand binding modes, diversify ligand chemical classes, and allow identification of new variants with balanced antiviral activity and metabolic stability. In the current work, we designed and synthesized three series of PF74-like analogs featuring conformational constraints at the aniline terminus or the phenylalanine carboxamide moiety, and characterized them using a biophysical thermal shift assay (TSA), cell-based antiviral and cytotoxicity assays, and in vitro metabolic stability assays in human and mouse liver microsomes. These studies showed that the two series with the phenylalanine carboxamide moiety replaced by a pyridine or imidazole ring can provide viable hits. Subsequent SAR identified an improved analog 15 which effectively inhibited HIV-1 (EC50 = 0.31 µM), strongly stabilized CA hexamer (ΔTm = 8.7 °C), and exhibited substantially enhanced metabolic stability (t1/2 = 27 min for 15 vs. 0.7 min for PF74). Metabolic profiles from the microsomal stability assay also indicate that blocking the C5 position of the indole ring could lead to increased resistance to oxidative metabolism.

Novel PF74-like small molecules targeting the HIV-1 capsid protein: Balance of potency and metabolic stability.

Of all known small molecules targeting human immunodeficiency virus (HIV) capsid protein (CA), PF74 represents by far the best characterized chemotype, due to its ability to confer antiviral phenotypes in both early and late phases of viral replication. However, the prohibitively low metabolic stability renders PF74 a poor antiviral lead. We report herein our medicinal chemistry efforts toward identifying novel and metabolically stable small molecules targeting the PF74 binding site. Specifically, we replaced the inter-domain-interacting, electron-rich indole ring of PF74 with less electron-rich isosteres, including imidazolidine-2,4-dione, pyrimidine-2,4-dione, and benzamide, and identified four potent antiviral compounds (10, 19, 20 and 26) with markedly improved metabolic stability. Compared to PF74, analog 20 exhibited similar submicromolar potency, and much longer (51-fold) half-life in human liver microsomes (HLMs). Molecular docking corroborated that 20 binds to the PF74 binding site, and revealed distinct binding interactions conferred by the benzamide moiety. Collectively, our data support compound 20 as a promising antiviral lead.

The importance of nurturing trusting relationships to embed shared decision-making during pregnancy and childbirth.

OBJECTIVE: To generate greater awareness of the contextual and relational factors that influence women's capacity to participate in shared decision-making during childbirth. METHODS: A three-phase participatory action research approach involving in-depth interviews and co-operative inquiry meetings. SETTING: Dublin, Ireland in a large maternity hospital. PARTICIPANTS: Five postnatal women who gave birth to live healthy babies, and attended obstetric or midwifery-led care and 13 practising midwives. FINDINGS: This paper presents the findings from the third phase of a three-phase action research study exploring the action's women consider necessary to embed informed choice, into practice. The findings reveal that multiple organisational and relational factors influence how women can participate in shared decision-making including the model of care they attended, continuity of carer, power dynamics, hospital policies and trust in self and others. Women's relationships with maternity care professionals reveals that exercising choice is not only defined by but contingent on the degree of trust in their relationships with maternity care professionals.

Co-Creating Descriptors and a Definition for Person-Centred Coordinated Health Care: An Action Research Study.

The aim of this study was to co-create a definition and generic descriptors for person-centred coordinated care for Ireland generated from service users' narratives. An overarching action research approach was used to engage and empower people to tangibly impact health policy and practice. Through focus groups and a qualitative survey, primary data were collected from a national sample of health services users, caregivers and health care service users' representative groups. Thematic analysis was used to analyse the data. Three major themes were co-produced as essential care elements. These were: 'My experience of healthcare', 'Care that I am confident in' and 'My journey through healthcare'. Through an IPPOSI partner project steering group and their membership groups' contribution, these themes were further refined into a definition of person-centred coordinated care and nineteen related generic descriptors. Key findings demonstrate that within complex, fragmented healthcare systems, the subjective expectations of service users should be integrated into care delivery, with a scaffolding of services to meet service users' needs between care settings and disciplines and over time.

Integrating Primary and Secondary Care to Enhance Chronic Disease Management: A Scoping Review.

BACKGROUND: In Ireland, as in many healthcare systems, health policy has committed to delivering an integrated model of care to address the increasing burden of chronic disease. Integrated care is an approach to healthcare systems delivery that aims to minimise fragmentation of patient services and improve care continuity. To this end, how best to integrate primary and secondary care is a challenge. This paper aims to undertake a scoping review of empirical work on the integration of primary and secondary care in relation to chronic disease management. METHODS: A search was conducted of 'PubMed', 'Cochrane Library' and 'Google Scholar' for papers published between 2009-2019 using Arksey and O'Malley's framework for conducing scoping reviews. RESULTS: Twenty-two studies were included. These reported research from a wide range of healthcare systems (most commonly UK, Australia, the Netherlands), adopted a range of methodologies (most commonly randomised/non-randomised controlled trials, case studies, qualitative studies) and among patients with a range of chronic conditions (most commonly diabetes, COPD, Parkinson's disease). No studies reported on interventions to address the needs of whole populations. Interventions to enhance integration included multidisciplinary teams, education of healthcare professionals, and e-health interventions. Among the effectiveness measures reported were improved disease specific outcomes, and cost effectiveness. CONCLUSION: With healthcare systems increasingly recognising that integrated approaches to patient care can enhance chronic disease management, considerable literature now informs how this can be done. However, most of the research published has focussed on specific diseases and their clinical outcomes. Future research should focus on how such approaches may improve health outcomes for populations as a whole.