IRE1α Mediates the Hypertrophic Growth of Cardiomyocytes Through Facilitating the Formation of Initiation Complex to Promote the Translation of TOP-Motif Transcripts.

BACKGROUND: Cardiomyocyte growth is coupled with active protein synthesis, which is one of the basic biological processes in living cells. However, it is unclear whether the unfolded protein response transducers and effectors directly take part in the control of protein synthesis. The connection between critical functions of the unfolded protein response in cellular physiology and requirements of multiple processes for cell growth prompted us to investigate the role of the unfolded protein response in cell growth and underlying molecular mechanisms. METHODS: Cardiomyocyte-specific inositol-requiring enzyme 1α (IRE1α) knockout and overexpression mouse models were generated to explore its function in vivo. Neonatal rat ventricular myocytes were isolated and cultured to evaluate the role of IRE1α in cardiomyocyte growth in vitro. Mass spectrometry was conducted to identify novel interacting proteins of IRE1α. Ribosome sequencing and polysome profiling were performed to determine the molecular basis for the function of IRE1α in translational control. RESULTS: We show that IRE1α is required for cell growth in neonatal rat ventricular myocytes under prohypertrophy treatment and in HEK293 cells in response to serum stimulation. At the molecular level, IRE1α directly interacts with eIF4G and eIF3, 2 critical components of the translation initiation complex. We demonstrate that IRE1α facilitates the formation of the translation initiation complex around the endoplasmic reticulum and preferentially initiates the translation of transcripts with 5' terminal oligopyrimidine motifs. We then reveal that IRE1α plays an important role in determining the selectivity and translation of these transcripts. We next show that IRE1α stimulates the translation of epidermal growth factor receptor through an unannotated terminal oligopyrimidine motif in its 5' untranslated region. We further demonstrate a physiological role of IRE1α-governed protein translation by showing that IRE1α is essential for cardiomyocyte growth and cardiac functional maintenance under hemodynamic stress in vivo. CONCLUSIONS: These studies suggest a noncanonical, essential role of IRE1α in orchestrating protein synthesis, which may have important implications in cardiac hypertrophy in response to pressure overload and general cell growth under other physiological and pathological conditions.

The inactivated infectious bronchitis virus (IBV) vaccine used as booster in layer hens influences the breadth of protection against challenge with IBV variants.

To achieve long term protection of laying and breeding hens against aberrant egg production caused by infectious bronchitis virus (IBV), a vaccination programme incorporating both live-attenuated and inactivated IBV vaccines is required. High quality IBV vaccines of both types are widely available, but the number of IBV variants of global importance continues to increase and it is not possible to develop vaccines against each one of them. Therefore, it is desirable to perform studies under controlled conditions to determine which IBV vaccine(s) provide the best protection for laying hens against different IBV challenges. Previous vaccination and challenge studies have shown that it is possible to obtain relevant data in a small number of laying hens housed under conditions of strict isolation. The present work extends this finding by investigating the efficacy, against challenge with five IBV strains of global importance, of an IBV vaccination programme including two live-attenuated IBV vaccines (Massachusetts and 793B types) and three different commercially available inactivated vaccines each containing antigen against at least one IBV strain. The results reported here confirm the importance of IBV vaccination for laying hens, show that efficient live priming makes a beneficial contribution to this protection and confirm that inactivated IBV vaccines contribute significantly to effective protection against at least the five IBV challenge strains used here. Furthermore, we provide data to support the "protectotype concept", long-established using different live-attenuated IBV vaccines in young chickens, is valid in broadening protection against IBV challenges in laying birds.RESEARCH HIGHLIGHTSIBV vaccination is essential as an aid in protecting laying hens against IBV infection.Live priming is a beneficial part of the IBV vaccination programme.IBV inactivated vaccine improves IBV protection.Heterologous IBV protection is confirmed in laying hens.

Implementation and evaluation of multilayered pressure injury prevention strategies in an Australian intensive care unit setting.

BACKGROUND: Pressure injuries are a ubiquitous, yet largely preventable, hospital acquired complication commonly seen in critically ill patients in the intensive care unit. OBJECTIVES: The objectives of this study were to implement targeted evidence-based pressure injury prevention strategies and evaluate their effect through measurement of patient pressure injury observations. METHODS: A prospective multiphased design was used in the intensive care unit of an Australian tertiary referral hospital using three study periods (period 1, weeks 1-18; period 2, weeks 19-28; and period 3, weeks 29-52). The interventions included staff-focused interventions and patient-focused interventions, with the latter defined in a work unit guideline. Weekly visual observations of critically ill patients' skin integrity were conducted by trained research nurses over 52 weeks from November 2015 to November 2016. The primary outcome measure was a pressure injury of any stage, identified at the weekly observation, and the effect of the intervention was evaluated through logistic regression. Reporting rigour has been demonstrated using the Standards for Quality Improvement Reporting Excellence checklist. RESULTS: Over the whole study, 15.4% (95% confidence interval [CI] = 12.6, 18.2%, 97/631) of patients developed a pressure injury, with the majority of these injuries (73.2%, 95% CI = 64.4%, 82.0%, 71/97) caused by medical devices. After adjustment for covariates known to influence hospital-acquired pressure injury development, pressure injury rates for period 3 compared with period 1 were reduced (odds ratio = 0.41, 95% CI = 0.20-0.97, p = 0.0126). CONCLUSIONS: We found the use of defined pressure injury prevention strategies targeted at both staff and patients reduced pressure injury prevalence.

Spotlight on avian coronaviruses.

Coronaviruses (CoVs) mainly cause enteric and/or respiratory signs. Mammalian CoVs including COVID-19 (now officially named SARS-CoV-2) belong to either the Alphacoronavirus or Betacoronavirus genera. In birds, the majority of the known CoVs belong to the Gammacoronavirus genus, whilst a small number are classified as Deltacoronaviruses. Gammacoronaviruses continue to be reported in an increasing number of avian species, generally by detection of viral RNA. Apart from infectious bronchitis virus in chickens, the only avian species in which CoV has been definitively associated with disease are the turkey, pheasant and guinea fowl. Whilst there is strong evidence for recombination between gammacoronaviruses of different avian species, and between betacoronaviruses in different mammals, evidence of recombination between coronaviruses of different genera is lacking. Furthermore, the recombination of an alpha or betacoronavirus with a gammacoronavirus is extremely unlikely. For recombination to happen, the two viruses would need to be present in the same cell of the same animal at the same time, a highly unlikely scenario as they cannot replicate in the same host!

Securement to prevent device-related pressure injuries in the intensive care unit: A randomised controlled feasibility study.

Medical device-related pressure injuries are the most common cause of pressure injuries within the intensive care unit, in particular those caused by nasogastric tubes and endotracheal tubes. There are several known methods, which can alleviate the pressure of these devices on the skin surface to reduce the rate of these injuries. To determine the feasibility of conducting a larger, adequately powered trial testing, several clinically effective interventions to reduce the incidence of medical device-related pressure injuries caused by these devices. Patients were recruited into both study arms and received one of three different methods of skin protection for both arms. Outcome measures included fidelity to the processes of care protocol, recruitment potential, and the number of medical device-related pressure injuries. Recruitment (n = 87) was slower than expected with less than 10% of screened potential patients available for enrolment. Fidelity to the process of care for each subgroup was variable with better adherence in the nasogastric tube arm compared to the endotracheal tube arm. This feasibility study has revealed concerns about the intervention designs and effectiveness as well as challenges for the adherence of the nursing staff to the protocol.

Spotlight on avian pathology: infectious bronchitis virus.

Infectious bronchitis is a highly infectious disease of the domestic chicken of all ages and type, affecting the respiratory, renal and reproductive systems. Secondary bacterial infections are common and have a serious economic and welfare impact. Many genotypic and serotypic variants of infectious bronchitis virus (IBV) exist worldwide, making diagnosis difficult, and challenging control strategies. Vaccination, requiring the use of both live-attenuated and inactivated vaccines, is needed to control IBV infections; to date, attempts to develop vectored vaccines as effective as the traditional vaccines have been unsuccessful.

Induction of IBV strain-specific neutralizing antibodies and broad spectrum protection in layer pullets primed with IBV Massachusetts (Mass) and 793B vaccines prior to injection of inactivated vaccine containing Mass antigen.

In an initial study in specified pathogen free (SPF) chickens, a heterologous virus neutralizing (VN) antibody response to IBV variants Q1, Variant 2 (Var 2), D388/QX (D388), D274 and Arkansas (DPI) was observed using a vaccination programme incorporating two different live-attenuated IBV vaccines, followed by boosting with an inactivated vaccine containing IBV Massachusetts (Mass) antigen. Therefore, a more detailed study was undertaken in SPF layer-type chickens primed with IBV Mass and 793B vaccines. The efficacy of single or repeated vaccination with a multivalent inactivated vaccine containing IBV antigen was determined against challenge with five virulent IBVs: Mass (M41), 793B (4/91), D388, Q1 and Var 2. The parameters assessed were serological response, respiratory signs, egg production, post mortem abnormalities in the reproductive organs and abdomen, and incidence of IBV antigen in kidneys. Increased VN titres were recorded against the five IBV challenge strains, with a significantly higher level of protection against drops in egg production following challenge. The difference between one or two vaccinations with inactivated vaccine was not significant in terms of egg production. However, a significantly increased level of protection was seen in the lower percentage of hens with free yolk in the abdomen and/or peritonitis post challenge with IBV variants, D388, Q1 and Var 2 not included in the vaccination programme. A lower incidence of acute, degenerated ovaries was found in groups given one injection of inactivated vaccine following live priming, and this was significantly lower than in groups given only live priming.

Combined exercise and nutritional rehabilitation in outpatients with incurable cancer: a systematic review.

PURPOSE: The optimal components for rehabilitation in patients with incurable cancer are unclear. However, principles of exercise and nutrition-based interventions used in cancer cachexia may be applied usefully to this population of cancer patients. This systematic review examines current evidence for rehabilitation combining exercise and nutritional support in patients with incurable cancer. METHODS: MEDLINE, EMBASE and Cochrane databases were searched. Eligible studies included patients with incurable cancer and rehabilitation programmes combining exercise and nutritional interventions. Studies of cancer survivors, curative treatments, reviews, case note reviews, protocols and abstracts were excluded. Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria were applied to patient-important outcomes. RESULTS: Of the 2424 search results, 67 abstracts were reviewed and 24 full texts examined. Eight studies (n = 685) were included comprising two randomised control trials, three prospective, one exploratory and two secondary analyses. All examined multi-modal outpatient programmes. GRADE analysis revealed moderate evidence (B) for improvements in depression and physical endurance, low-quality evidence (C) for quality of life and fatigue and very low-quality evidence (D) for overall function and nutritional status. CONCLUSION: There are limited data for multi-modal rehabilitation programmes combining exercise and nutritional interventions in patients with incurable cancer. However, studies to date report improvements in multiple domains, most notably physical endurance and depression scores. This supports the concept that multi-modal rehabilitation incorporating principles of cachexia management may be appropriate for the wider group of patients with incurable cancer. Further, high-quality studies are needed to define the optimal approach and outcome measures.

Exploring Incontinence-Associated Dermatitis in a Single Center Intensive Care Unit: A Longitudinal Point Prevalence Survey.

PURPOSE: The purpose of this study was to provide longitudinal prevalence rates of incontinence-associated dermatitis (IAD) in patients in an intensive care unit (ICU) and to identify patient characteristics associated with IAD development. DESIGN: Prospective observational. SUBJECTS AND SETTING: The sample comprised 351 patients aged 18 years and older in a major metropolitan public hospital ICU in Queensland, Australia. METHODS: All consenting, eligible participants at risk of developing IAD underwent weekly skin inspections to determine the presence of IAD. Data were collected weekly for 52 consecutive weeks. Descriptive statistics described the study sample and logistic regression analysis was used to identify patient characteristics associated with development of IAD. RESULTS: The weekly IAD prevalence ranged between 0% and 70%, with IAD developing in 17% (n = 59/351) of ICU patients. The odds of IAD developing increased statistically significantly with increasing age (odds ratio [OR]: 1.029, 95% confidence interval [CI]: 1.005-1.054, P = .016), time in the ICU (OR = 1.104; 95% CI: 1.063-1.147, P < .001), and Bristol Stool chart score (OR = 4.363, 95% CI: 2.091-9.106, P < .001). Patients with respiratory (OR = 3.657, 95% CI: 1.399-9.563, P = .008) and sepsis (OR = 3.230, 95% CI: 1.281-8.146, P = .013) diagnoses had increased odds of developing IAD. CONCLUSIONS: These data show the high variability of IAD prevalence over a 1-year period. Characteristics associated with the development of IAD in patients in the ICU included older age, longer lengths of ICU stay, incontinent of liquid feces, and having respiratory or sepsis diagnoses.

Safety culture in intensive care internationally and in Australia: A narrative review of the literature.

OBJECTIVE: Assessment of safety culture in health care is of particular relevance in the complex intensive care setting, where the effects of human error can have catastrophic consequences. The aim of this review was to examine the literature on safety culture in intensive care units (ICUs) and specifically, to explore the state of knowledge regarding safety culture in the context of Australian ICUs. METHODS: A search was conducted of key databases for studies published in English between January 2008 and December 2017 using terms 'safety culture', 'safety climate', 'safety attitude', 'intensive care', 'ICU' and 'critical care'. Studies were included if they presented original research, utilised the teamwork and safety climate factors of a quantitative survey tool to assess safety culture, the sample population included participants working in an adult intensive care, and the findings were reported in the context of intensive care. RESULTS: Of the 36 studies identified, two were conducted in Australia. The studies demonstrate a rapid expansion in safety culture assessment globally. Three levels of safety culture application in intensive care were identified, including safety culture assessment, effect of an intervention on safety culture, and evaluation of the association between safety culture and structural, process and outcomes measures. The use of targeted safety culture domains is emerging. Common findings included variation in perceptions of safety culture between ICUs, unit and hospital management, and professional groups. CONCLUSION: Though the assessment of safety culture in ICUs has been an area of prolific research internationally over the past ten years, the Australian context is limited and could be advanced through further research, including the effect on safety culture of interventions, and to establish the association between safety culture and patient safety outcomes. Longitudinal studies to demonstrate sustained intervention effects on safety culture should be considered.

Understanding contextual barriers and enablers to pressure injury prevention practice in an Australian intensive care unit: An exploratory study.

BACKGROUND: Skin integrity management is often a low clinical priority in the intensive care environment, possibly resulting in high pressure injury (PI) prevalence. This article reports the results of the first phase of a multiphased project, "Translating evidence-based pressure injury prevention strategies to the intensive care environment (SUSTAIN study)". The SUSTAIN study used a research translation framework to guide the assessment of research uptake, development, and monitoring of translational strategies to reduce PIs. OBJECTIVE: The objective was to assess the enablers and barriers to research translation of evidence-based skin integrity management in one Australian tertiary referral intensive care unit (ICU). METHODS: This exploratory study was conducted in an Australian metropolitan tertiary ICU on a sample of 204 registered nurses. Data were collected using (i) a descriptive cross-sectional cohort survey of barriers, enablers, and attitudes to PI prevention, (ii) a cross-sectional survey of PI knowledge, and (iii) focus groups to understand the local contextual factors impacting registered nurses' PI prevention practice. RESULTS: Participants reported a moderate to high ability to rise above barriers in PI prevention, a positive attitude towards PI prevention, and considered this a priority in their care of patients. High patient acuity emerged as a barrier to implementing timely PI prevention strategies. In the knowledge, test participants with postgraduate qualifications answered more statements correctly. Focus group data revealed four themes: (i) team ICU, (ii) processes of care, (iii) education for consistency, and (iv) the patient. CONCLUSIONS: It is essential that evidence-based PI prevention strategies are provided in the intensive care environment. Our findings indicate that despite positive attitudes and sound knowledge levels, high patient acuity is a significant barrier to evidence implementation.

Surveillance of adverse events following immunisation in Australia, 2015.

This report summarises Australian passive surveillance data for adverse events following immunisation (AEFI) for 2015 reported to the Therapeutic Goods Administration and compares them to long-term trends. There were 2,924 AEFI records for vaccines administered in 2015; an annual AEFI reporting rate of 12.3 per 100,000 population. There was a decline of 7% in the overall AEFI reporting rate in 2015 compared with 2014. This decline in reported adverse events in 2015 compared to the previous year was mainly attributable to fewer reports following the HPV vaccine and replacement of monovalent vaccines (Hib, MenCCV and varicella) with combination vaccines such as Hib-MenC, and MMRV. AEFI reporting rates for most individual vaccines were lower in 2015 compared with 2014. The most commonly reported reactions were injection site reaction (26%), pyrexia (17%), rash (16%), vomiting (8%) and headache (7%). The majority of AEFI reports (85%) were described as non-serious events. There were two deaths reported, but no clear causal relationship with vaccination was found.

Pressure injury prevalence in intensive care versus non-intensive care patients: A state-wide comparison.

BACKGROUND: Hospital-acquired pressure injury is associated with increased morbidity and mortality and considered to be largely preventable. Pressure injury prevalence is regarded as a marker of health care quality. OBJECTIVE: To compare the state-wide prevalence, severity and location of pressure injuries of intensive care unit patients compared to patients in non-intensive care wards. METHOD: The study employed a secondary data analysis design to extract and analyse de-identified pressure injury data from all Queensland Health hospitals with level I-III intensive care facilities that participated in Queensland Bedside Audits between 2012-2014. The sample included all adult ICU and non-ICU patients that provided consent for the Queensland Bedside Audits, excluding those in mental health units. RESULTS: Excluding Stage I, overall hospital-acquired pressure injury prevalence from 2012 to 2014 was 11% for intensive care patients and 3% for non-intensive care patients. Intensive care patients were 3.8 times more likely (RR 2.7-5.4, 95% CI) than non-intensive care patients to develop a pressure injury whilst in hospital. The sacrum/coccyx was the most common site of hospital-acquired pressure injury in all patients (intensive care patients 22%; non-intensive care patients 35%) however, mucosal pressure injury proportion was significantly higher in intensive care patients (22%) than in non-intensive care patients (2%). Stage II HAPI prevalence was the most common stage reported, 53% for intensive care patients compared to 63% for non-intensive care patients. CONCLUSION: There are significant differences in hospital-acquired pressure injury prevalence by stage and location between intensive care and non-intensive care patients reflecting the possible impact of critical illness on the development of skin injury. This has implications for resource funding for pressure injury prevention and the imposition of government initiated financial penalties for hospital-acquired pressure injury. For future comparisons to be effective between intensive care units, benchmarking partners should share similar characteristics and relevant targets.

Image quality and dose differences caused by vendor-specific image processing of neonatal radiographs.

BACKGROUND: Image processing plays an important role in optimizing image quality and radiation dose in projection radiography. Unfortunately commercial algorithms are black boxes that are often left at or near vendor default settings rather than being optimized. OBJECTIVE: We hypothesize that different commercial image-processing systems, when left at or near default settings, create significant differences in image quality. We further hypothesize that image-quality differences can be exploited to produce images of equivalent quality but lower radiation dose. MATERIALS AND METHODS: We used a portable radiography system to acquire images on a neonatal chest phantom and recorded the entrance surface air kerma (ESAK). We applied two image-processing systems (Optima XR220amx, by GE Healthcare, Waukesha, WI; and MUSICA(2) by Agfa HealthCare, Mortsel, Belgium) to the images. Seven observers (attending pediatric radiologists and radiology residents) independently assessed image quality using two methods: rating and matching. Image-quality ratings were independently assessed by each observer on a 10-point scale. Matching consisted of each observer matching GE-processed images and Agfa-processed images with equivalent image quality. A total of 210 rating tasks and 42 matching tasks were performed and effective dose was estimated. RESULTS: Median Agfa-processed image-quality ratings were higher than GE-processed ratings. Non-diagnostic ratings were seen over a wider range of doses for GE-processed images than for Agfa-processed images. During matching tasks, observers matched image quality between GE-processed images and Agfa-processed images acquired at a lower effective dose (11 ± 9 µSv; P < 0.0001). CONCLUSION: Image-processing methods significantly impact perceived image quality. These image-quality differences can be exploited to alter protocols and produce images of equivalent image quality but lower doses. Those purchasing projection radiography systems or third-party image-processing software should be aware that image processing can significantly impact image quality when settings are left near default values.

Community nursing quality indicators for end-of-life care in England: identification, preparation, and coordination.

High-quality community nursing is essential to ensure that end-of-life care can be provided in community settings in line with patient preferences. This article examines the quality priorities commissioners sought to incentivise in end-of-life care, by reviewing a survey of Commissioning for Quality and Innovation (CQUIN) indicators for community nursing conducted in England in 2014-2015. Findings from the survey suggest that end-of-life care was not given a high priority with the CQUIN indicators for community nursing. Vigorous quality standards, including training and development, need to be in place to make sure that the potential of community nursing is being used to sensitively engage with people nearing the end of their lives and support them to plan their future care, if they so wish.

Surveillance of adverse events following immunisation in Australia annual report, 2013.

This report summarises Australian passive surveillance data for adverse events following immunisation (AEFI) for 2013 reported to the Therapeutic Goods Administration (TGA) for 2013 and describes reporting trends over the 14-year period 1 January 2000 to 31 December 2013. There were 3,161 AEFI records for vaccines administered in 2013. This is an annual AEFI reporting rate of 13.9 per 100,000 population, the 2nd highest since 2000 and an increase of 59% compared with 2012 (1,994 AEFI records; 8.8 per 100,000 population). The increase was partly due to implementation of enhancements to vaccine safety reporting. This included stimulated reporting of AEFI as part of the extension of national human papillomavirus (HPV) vaccination under the National Immunisation Program to males aged 12-13 years, along with a catch-up program for males aged 14 and 15 years in February 2013 (n=785; includes males and females), in which certain events, such as syncope, were closely monitored. Eighty-two per cent (n=341/414) of the syncope reports were following HPV vaccination and of these 57% (n=195) were males and 43% (n=146) were females. In addition, reporting rates for most other the vaccines were higher in 2013 compared with 2012. The majority of AEFI reports described non-serious events while 5% (n=158) were classified as serious. There were 4 reports of death; however, all deaths were investigated by the TGA and no clear causal relationship with vaccination was found. The most commonly reported reactions were injection site reaction (13%), rash (10%), pyrexia (8%), and syncope (7%).

How commissioning affects community nursing.

Community nurses have direct experience of how changes in the local health economy affect the quality of care patients receive, so it is important that they engage with commissioning to influence decisions made about the quality and direction of their service. This article seeks to demystify commissioning priorities by drawing on findings from a survey of Commissioning for Quality and Innovation indicators for community nursing conducted in England, 2014-15. The article focuses specifically on organisational goals, highlighting the impact of the Francis report and other NHS priorities on quality assessment in community nursing.

Factors influencing the outcome of infectious bronchitis vaccination and challenge experiments.

The factors influencing the outcome of infectious bronchitis vaccination and challenge experiments regarding the respiratory and renal systems are reviewed. Advantages and disadvantages of the available techniques for measuring protection against an infectious bronchitis virus challenge are discussed, including the definition of protection itself. Suggestions are made regarding some ways in which progress towards standardization of a recognized protocol for performing experimental challenge studies can be made and areas where more work is needed are indicated.

Surveillance of adverse events following immunisation in Australia, 2012.

This report summarises Australian passive surveillance data for adverse events following immunisation (AEFI) reported to the Therapeutic Goods Administration (TGA) for 2012. It also describes reporting trends over the 13-year period 1 January 2000 to 31 December 2012. There were 1,897 AEFI records for vaccines administered in 2012, a decrease of 22% from 2,417 in 2011. The decrease in 2012 compared with 2011 was mainly attributable to a drop in the reports following receipt of the 23-valent pneumococcal polysaccharide vaccine (405 reduced to 133). However, reporting rates for some other vaccines such as rotavirus and varicella vaccines were higher in 2012 than 2011. Although an increase was observed in estimated reporting rates for rotavirus and varicella in children aged < 7 years in 2012 compared with 2011, it was not statistically significant. There were 370 AEFI records (37.2 per 100,000 doses) for the pneumococcal conjugate vaccine in 2012, which was fewer than in 2011 (43.4 per 100,000 doses). The most commonly reported reactions were injection site reactions (40%), fever (22%), allergic reactions (19%) and rash (10%). Only 7% of all the reported adverse events were categorised as serious. There were 2 reports of death, which were investigated by the TGA and no clear causal relationship with vaccination was found.