Increasing Effectiveness of the Surgical Airway Response System: Introduction of the Otolaryngology Airway Pager, Quality Improvement Project of the PGY-2 Class

Introduction: The need for an Otolaryngology airway pager is based on several external and internal factors. The current communication pathway for emergent airways at our institution is well established but often misinterpreted. The protocol is outlined in Figure 1. The priority to reach out to other departments is based on their availability of an attending in house overnight. Furthermore, there is often a delay in contacting the Otolaryngology department. Our service has multiple pagers to accommodate for each of our inpatient teams, which can be confusing for other services. One of the driving events for this project was an incident at JHN where a tracheostomy tube became dislodged. There were several attempts to contact our team through the wrong pager and by the time we were notified the patient had expired. In addition our personal cell phones are commonly used as the primary means of contact for urgent situations. On several occasions the wrong person has been called in the middle of the night or the on-call resident is contacted while they are in the operating room during the day, resulting in a slower response time. From the perspective of the Otolaryngology Department at times we receive multiple pages and answer in the order that the pages were received, not in order of acuity as this is unknown. A dedicated airway pager will help us prioritize our decisions most safely.https://jdc.jefferson.edu/patientsafetyposters/1067/thumbnail.jp

Severe Acute Respiratory Syndrome Coronavirus nsp9 Dimerization Is Essential for Efficient Viral Growth

The severe acute respiratory syndrome coronavirus (SARS-CoV) devotes a significant portion of its genome to producing nonstructural proteins required for viral replication. SARS-CoV nonstructural protein 9 (nsp9) was identified as an essential protein with RNA/DNA-binding activity, and yet its biological function within the replication complex remains unknown. Nsp9 forms a dimer through the interaction of parallel α-helices containing the protein-protein interaction motif GXXXG. In order to study the role of the nsp9 dimer in viral reproduction, residues G100 and G104 at the helix interface were targeted for mutation. Multi-angle light scattering measurements indicated that G100E, G104E, and G104V mutants are monomeric in solution, thereby disrupting the dimer. However, electrophoretic mobility assays revealed that the mutants bound RNA with similar affinity. Further experiments using fluorescence anisotropy showed a 10-fold reduction in RNA binding in the G100E and G104E mutants, whereas the G104V mutant had only a 4-fold reduction. The structure of G104E nsp9 was determined to 2.6-Å resolution, revealing significant changes at the dimer interface. The nsp9 mutations were introduced into SARS-CoV using a reverse genetics approach, and the G100E and G104E mutations were found to be lethal to the virus. The G104V mutant produced highly debilitated virus and eventually reverted back to the wild-type protein sequence through a codon transversion. Together, these data indicate that dimerization of SARS-CoV nsp9 at the GXXXG motif is not critical for RNA binding but is necessary for viral replication

WRR4, a broad-spectrum TIR-NB-LRR gene from Arabidopsis thaliana that confers white rust resistance in transgenic oilseed brassica crops

White blister rust caused by Albugo candida (Pers.) Kuntze is a common and often devastating disease of oilseed and vegetable brassica crops worldwide. Physiological races of the parasite have been described, including races 2, 7 and 9 from Brassica juncea, B. rapa and B. oleracea, respectively, and race 4 from Capsella bursa-pastoris (the type host). A gene named WRR4 has been characterized recently from polygenic resistance in the wild brassica relative Arabidopsis thaliana (accession Columbia) that confers broad-spectrum white rust resistance (WRR) to all four of the above Al. candida races. This gene encodes a TIR-NB-LRR (Toll-like/interleukin-1 receptor-nucleotide binding-leucine-rich repeat) protein which, as with other known functional members in this subclass of intracellular receptor-like proteins, requires the expression of the lipase-like defence regulator, enhanced disease susceptibility 1 (EDS1). Thus, we used RNA interference-mediated suppression of EDS1 in a white rust-resistant breeding line of B. napus (transformed with a construct designed from the A. thaliana EDS1 gene) to determine whether defence signalling via EDS1 is functionally intact in this oilseed brassica. The eds1-suppressed lines were fully susceptible following inoculation with either race 2 or 7 isolates of Al. candida. We then transformed white rust-susceptible cultivars of B. juncea (susceptible to race 2) and B. napus (susceptible to race 7) with the WRR4 gene from A. thaliana. The WRR4-transformed lines were resistant to the corresponding Al. candida race for each host species. The combined data indicate that WRR4 could potentially provide a novel source of white rust resistance in oilseed and vegetable brassica crops

Cellular prion protein (PrPC) in the development of Merlin-deficient tumours

Loss of function mutations in the neurofibromatosis Type 2 (NF2) gene, coding for a tumour suppressor, Merlin, cause multiple tumours of the nervous system such as schwannomas, meningiomas and ependymomas. These tumours may occur sporadically or as part of the hereditary condition neurofibromatosis Type 2 (NF2). Current treatment is confined to (radio) surgery and no targeted drug therapies exist. NF2 mutations and/or Merlin inactivation are also seen in other cancers including some mesothelioma, breast cancer, colorectal carcinoma, melanoma and glioblastoma. To study the relationship between Merlin deficiency and tumourigenesis, we have developed an in vitro model comprising human primary schwannoma cells, the most common Merlin-deficient tumour and the hallmark for NF2. Using this model, we show increased expression of cellular prion protein (PrPC) in schwannoma cells and tissues. In addition, a strong overexpression of PrPC is observed in human Merlin-deficient mesothelioma cell line TRA and in human Merlin-deficient meningiomas. PrPC contributes to increased proliferation, cell-matrix adhesion and survival in schwannoma cells acting via 37/67 kDa non-integrin laminin receptor (LR/37/67 kDa) and downstream ERK1/2, PI3K/AKT and FAK signalling pathways. PrPC protein is also strongly released from schwannoma cells via exosomes and as a free peptide suggesting that it may act in an autocrine and/or paracrine manner. We suggest that PrPC and its interactor, LR/37/67 kDa, could be potential therapeutic targets for schwannomas and other Merlin-deficient tumours

Protocol of a longitudinal cohort study on physical activity behaviour in physically disabled patients participating in a rehabilitation counselling programme: ReSpAct

Introduction: Stimulating physical activity behaviour in persons with a physical disability is important, especially after discharge from rehabilitation. A tailored counselling programme covering both the period of the rehabilitation treatment and the first months at home seems on the average effective. However, a considerable variation in response is observed in the sense that some patients show a relevant beneficial response while others show no or only a small response on physical activity behaviour. The Rehabilitation, Sports and Active lifestyle (ReSpAct) study aims to estimate the associations of patient and programme characteristics with patients' physical activity behaviour after their participation in a tailored counselling programme. Methods and analysis: A questionnaire-based nationwide longitudinal prospective cohort study is conducted. Participants are recruited from 18 rehabilitation centres and hospitals in The Netherlands. 2000 participants with a physical disability or chronic disease will be followed during and after their participation in a tailored counselling programme. Programme outcomes on physical activity behaviour and patient as well as programme characteristics that may be associated with differences in physical activity behaviour after programme completion are being assessed. Data collection takes place at baseline and 14, 33 and 52 weeks after discharge from rehabilitation. Ethics and dissemination: The study protocol has been approved by the Medical Ethics Committee of the University Medical Centre Groningen and at individual participating institutions. All participants give written informed consent. The study results will provide new insights into factors that may help explain the differences in physical activity behaviour of patients with a physical disability after they have participated in the same physical activity and sports stimulation programme. Thereby, it will support healthcare professionals to tailor their guidance and care to individual patients in order to stimulate physical activity after discharge in a more efficient and effective way

Euforea treatment algorithm for allergic rhinitis

Non peer reviewe

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or \u27scaffold\u27) of haplotypes across each chromosome. We then phase the sequence data \u27onto\u27 this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved