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Background/AimsThe importance of viral respiratory infections (VRI) in exacerbations of bronchiectasis is poorly understood. However, they have been proposed as the microbiological ‘trigger’ for bronchiectasis exacerbations.The aims of this study were to describe the rate of VRI in patients hospitalized with bronchiectasis exacerbations and evaluate their effects on exacerbation severity.MethodsAdult patients hospitalised with acute respiratory illness to two hospitals in Auckland, New Zealand between 2012–2015 were screened for inclusion in the Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance (SHIVERS) project, a population-based virus surveillance study. Nasopharyngeal sampling was used to test for respiratory viruses using real-time PCR. Patients with bronchiectasis were identified using ICD-10 code J47, ‘bronchiectasis’.Individual patient data and electronic patient records were reviewed; patients with bronchiectasis due to cystic fibrosis were excluded, as were patients with no clinical evidence of bronchiectasis. Pre-specified parameters were used to describe severity of exacerbation.Results526 patients with bronchiectasis experienced 979 admissions with acute respiratory illnesses. Nasopharyngeal sampling for VRI was performed in 429 admissions (43.8%). Of these, 154 (35.9%) tested positive for VRI, including 62 (14.4%) cases of influenza, 59 rhinovirus (13.8%) and 20 RSV (4.7%). 11 patients (2.5%) tested positive for more than one respiratory virus.Median LOS was longer for patients with VRI (5 [3–7] vs 4 days [2–6] respectively, p=0.032). Patients with VRI were more likely to receive non-invasive ventilation (3.9% vs. 0.8%, p=0.022), and more likely to have a fever (76% vs. 66%, p=0.034). 4.4% of patients died within 30 days of their first recorded admission, and 16.2% died within a year, with no difference between patients testing positive or negative for VRI.ConclusionsTo our knowledge, this is the largest study to investigate the role of viral respiratory infection in patients with bronchiectasis exacerbations. VRI is common in exacerbations requiring hospitalisation and is associated with some markers of more severe illness, including longer duration of hospital admission. Influenza was the most common viral infection, highlighting the importance of public health measures against influenza and other viruses, including vaccination and testing, to limit the effects of viral respiratory infection in bronchiectasis.

IntroductionThe prevalence of bronchiectasis in New Zealand (NZ) is higher than comparable countries (180/100,000 population)1; the burden and severity of disease are incompletely understood. Bronchiectasis registries such as EMBARC (>14,000 participants) and the Australian Bronchiectasis Registry (ABR, 1360 participants) have improved understanding of bronchiectasis and identified future research priorities. The aim of the NZ Bronchiectasis Registry (NZBR) is to contribute to the understanding of bronchiectasis aetiology and management, both in NZ and internationally. It is closely aligned with ABR and supported by Lung Foundation Australia.MethodsNZBR shares data fields with ABR and EMBARC, with additional fields to reflect unique socio-demographic characteristics of NZ participants. NZBR is a multi-centre, prospective, observational study enrolling consecutive patients in NZ. Participants are identified from existing clinical and research databases, and from inpatient and outpatient encounters. Eligible adult participants have a clinical diagnosis of bronchiectasis, excluding cystic fibrosis, confirmed on CT thorax. All participants are seen face-to-face and provide written consent.Demographics, clinical information, exacerbation history (including antibiotic prescription data) and health-related quality of life assessment are collected at enrolment and annual review. Data is entered into a secure online platform, which sits alongside ABR in REDCap.ResultsNational ethical approval is in place. Enrolment began at the primary site in June 2018, shortly followed by a second site. Two additional sites have local research governance approval. To date, 117 participants have been enrolled across 2 sites: 63/117 females (53.8%); mean age 62.4 (±15.6) years. 45/117 (38.4%) of participants are of M ori or Pacific Island origin; 41/117 (35.0%) participants live in the most deprived socioeconomic quintile.ConclusionThese early steps have paved the way for a national bronchiectasis registry and are an early indicator of health inequalities for bronchiectasis in NZ. NZBR will contribute to a regional Australasian Bronchiectasis Registry to create a comprehensive longitudinal dataset across Australia and NZ, to help establish the burden of disease, promote changes in clinical practice and improve clinical outcomes. Future plans include addition of paediatric sites and increased collaboration with international registries.ReferenceTelfar Barnard L, Zhang J. Asthmaand Respiratory Foundation New Zealand; 2017.

IntroductionAcquiring competency in thoracic ultrasound (USS) is mandatory for all respiratory trainees by the end of ST5, but it is often challenging for trainees to meet the requirements in current RCR guidelines for level 1 competency (≥1 session/week over≥three months, with 5 scans per session performed by trainee). We aimed to clarify where thoracic ultrasound training opportunities currently exist for respiratory registrars to inform further debate around the competency framework.MethodsTrainees in the South west, North West and Oxford deaneries were invited to submit data on numbers of thoracic USS performed by both radiology departments (specifying numbers of scans per morning/afternoon session) and respiratory teams (specifying pleural clinic/procedure list/respiratory ward/other ward or clinic) over a randomly selected 4 week period between January and May 2017. Data was to represent total number of scans performed within each department, not number of scans done by one individual.ResultsData was provided from 14 hospitals (6 South West, 7 North West, 1 Oxford) including 3 tertiary pleural centres. Results are shown in Table 1. Full Results from 2 centres represent estimated numbers and one site (North Manchester) submitted 3 weeks data. There was no radiology session in any hospital with ≥5 thoracic ultrasound sans performed (out of total of 55 weeks sampled across all sites).ConclusionsIn almost all surveyed hospitals from two deaneries, and a tertiary centre from a third, the majority of thoracic ultrasound is performed by respiratory teams rather than radiologists and in a variety of elective and unscheduled situations. Similarly the principle opportunity for USS training exists within the respiratory team and is deliverable out-with the tertiary setting. The currently recommended exposure of regularly attending a list or session to undertake 5 USS is not achievable in radiology departments even where thoracic USS is being performed, including surveyed tertiary pleural centres. Future recommendations on USS training requirements for respiratory trainees need to be flexible to take account of where opportunities exist and should recognise the role that both radiology and respiratory teams provide.Abstract P238 Table 1Numbers of thoracic USS examinations performed by radiology and respiratory departments

This article reflects on how schools may become truly learning organisations. In it the author explores interesting concepts on how organisations have to change if they are to be relevant to the learning needs of students. Change involves risk taking, but in a context where the absolute integrity of the person and the community is respected.

Introduction Autism spectrum disorder (ASD) affects 1 in 68 children, is characterized by impaired social interaction and communication as well as restricted or repetitive behaviors, and varies widely with respect to its causes and presentations. There are no validated pharmacologic treatments for the core symptoms of ASD. The social, medical, and economic burdens of ASD on families and caregivers are profound. We recently showed in a small clinical trial that sulforaphane (SF) from broccoli sprouts could significantly reduce the behavioral symptoms of ASD. Methods After we completed the intervention phase of the original trial (2011–2013), many caregivers used over-the-counter dietary SF supplements in order to attempt to maintain improvements similar to those noted during the intervention. We periodically followed the progress of study participants through the summer of 2016. Results Families of 16 of the 26 subjects who received SF as part of the original study responded to requests for further information. Of these subjects, 6 did not continue taking SF supplements after the study. Nine of the 16 subjects are still taking an SF supplement and a 10th planned to. We present the edited testimonials of their caregivers in this case series. Conclusions Many parents and caregivers articulated the positive effects of SF, both during the intervention phase and in the ensuing 3 years reported herein. These observations may contribute to understanding ASD and to treatments that may alleviate some of its symptoms. Diet- and supplement-based therapies deserve careful consideration for their potential to provide vital clinical as well as biochemical information about ASD.

Human cytomegalovirus (HCMV) encodes multiple putative G protein-coupled receptors (GPCRs). US28 functions as a viral chemokine receptor and is expressed during both latent and lytic phases of virus infection. US28 actively promotes cellular migration, transformation, and plays a major role in mediating viral latency and reactivation; however, knowledge about the interaction partners involved in these processes is still incomplete. Herein, we utilized a proximity-dependent biotinylating enzyme (TurboID) to characterize the US28 interactome when expressed in isolation, and during both latent (CD34 + hematopoietic progenitor cells) and lytic (fibroblasts) HCMV infection. Our analyses indicate that the US28 signalosome converges with RhoA and EGFR signal transduction pathways, sharing multiple mediators that are major actors in processes such as cellular proliferation and differentiation. Integral members of the US28 signaling complex were validated in functional assays by immunoblot and small-molecule inhibitors. Importantly, we identified RhoGEFs as key US28 signaling intermediaries. In vitro latency and reactivation assays utilizing primary CD34 + hematopoietic progenitor cells (HPCs) treated with the small-molecule inhibitors Rhosin or Y16 indicated that US28 –RhoGEF interactions are required for efficient viral reactivation. These findings were recapitulated in vivo using a humanized mouse model where inhibition of RhoGEFs resulted in a failure of the virus to reactivate. Together, our data identifies multiple new proteins in the US28 interactome that play major roles in viral latency and reactivation, highlights the utility of proximity-sensor labeling to characterize protein interactomes, and provides insight into targets for the development of novel anti-HCMV therapeutics.

Human cytomegalovirus (HCMV) is a highly prevalent beta-herpesvirus and a significant cause of morbidity and mortality following hematopoietic and solid organ transplant, as well as the leading viral cause of congenital abnormalities. A key feature of the pathogenesis of HCMV is the ability of the virus to establish a latent infection in hematopoietic progenitor and myeloid lineage cells. Human cytomegalovirus (HCMV) is a highly prevalent beta-herpesvirus and a significant cause of morbidity and mortality following hematopoietic and solid organ transplant, as well as the leading viral cause of congenital abnormalities. A key feature of the pathogenesis of HCMV is the ability of the virus to establish a latent infection in hematopoietic progenitor and myeloid lineage cells. The study of HCMV latency has been hampered by difficulties in obtaining and culturing primary cells, as well as an inability to quantitatively measure reactivating virus, but recent advances in both in vitro and in vivo models of HCMV latency and reactivation have led to a greater understanding of the interplay between host and virus. Key differences in established model systems have also led to controversy surrounding the role of viral gene products in latency establishment, maintenance, and reactivation. This review will discuss the details and challenges of various models including hematopoietic progenitor cells, monocytes, cell lines, and humanized mice. We highlight the utility and functional differences between these models and the necessary experimental design required to define latency and reactivation, which will help to generate a more complete picture of HCMV infection of myeloid-lineage cells.

Currently, our son's school, Kerrisdale elementary, is the seventh most high-risk school in the Vancouver area in the event of an earthquake. A structural engineering assessment of this unreinforced masonry brick building revealed that the exterior walls would collapse or peel away from the floors even in a minor earthquake.

Each herpesvirus family establishes latency in a unique cell type. Since herpesviruses genomes are maintained as episomes, the viruses need to devise mechanisms to retain the latent genome during cell division. Human cytomegalovirus (HCMV) microRNAs play essential roles in latency and reactivation in CD34 + hematopoietic progenitor cells (HPCs) via regulation of viral and cellular gene expression. In the present study, we show that HCMV miR-US25-1 targets RhoA, a small GTPase required for CD34 + HPC self-renewal, proliferation, and hematopoiesis. Expression of miR-US25-1 impairs signaling through the nonmuscle myosin II light chain, which leads to a block in cytokinesis and an inhibition of proliferation. Moreover, infection with an HCMV mutant lacking miR-US25-1 resulted in increased proliferation of CD34 + HPCs and a decrease in the proportion of genome-containing cells at the end of latency culture. These observations provide a mechanism by which HCMV limits proliferation to maintain latent viral genomes in CD34 + HPCs. IMPORTANCE Each herpesvirus family establishes latency in a unique cell type. Since herpesvirus genomes are maintained as episomes, the virus needs to devise mechanisms to retain the latent genome during cell division. Alphaherpesviruses overcome this obstacle by infecting nondividing neurons, while gammaherpesviruses tether their genome to the host chromosome in dividing B cells. The betaherpesvirus human cytomegalovirus (HCMV) establishes latency in CD34 + hematopoietic progenitor cells (HPCs), but the mechanism used to maintain the viral genome is unknown. In this report, we demonstrate that HCMV miR-US25-1 downregulates expression of RhoA, a key cell cycle regulator, which results in inhibition of CD34 + HPC proliferation by blocking mitosis. Mutation of miR-US25-1 during viral infection results in enhanced cellular proliferation and a decreased frequency of genome-containing CD34 + HPCs. These results reveal a novel mechanism through which HCMV is able to regulate cell division to prevent viral genome loss during proliferation.