Transversus Abdominis Plane (TAP) Block Education

Severe pain in the genitourinary (GU) population after abdominal surgery remains a major problem, that can impact surgical healing, recovery of bowel function, and prolong hospital length of stay. The current gold standard for managing postoperative pain includes opioid administration, such as fentanyl, hydromorphone and morphine. Inadequate pain control and excessive opioid use after abdominal surgery are associated with numerous adverse effects. The utilization of transversus abdominis plane (TAP) blocks during abdominal surgeries have shown to provide postoperative pain relief and decrease opioid consumption. A large government hospital is implementing TAP blocks in their GU division. Prior to their implementation, the Doctoral of Nursing Practice (DNP) candidates facilitated a didactic and simulation-based teaching about TAP blocks to improve providers knowledge and competency. This evidence-based practice project followed a descriptive design that consisted of a pre-test, immediate post-test, and a one-month post-test. Eleven study participants were analyzed using repeated measures across three time points. A statistically significant increase in overall knowledge scores (p = 0.023) was observed. Education and simulation prior to implementation of a new clinical intervention is vital for its success. The increase in median test scores demonstrates the success of the project’s design and sheds light on its future implications for robust knowledge dissemination

Further evidence for the involvement of EFL1 in a Shwachman-Diamond-like syndrome and expansion of the phenotypic features.

Recent evidence has implicated EFL1 in a phenotype overlapping Shwachman-Diamond syndrome (SDS), with the functional interplay between EFL1 and the previously known causative gene SBDS accounting for the similarity in clinical features. Relatively little is known about the phenotypes associated with pathogenic variants in the EFL1 gene, but the initial indication was that phenotypes may be more severe, when compared with SDS. We report a pediatric patient who presented with a metaphyseal dysplasia and was found to have biallelic variants in EFL1 on reanalysis of trio whole-exome sequencing data. The variant had not been initially reported because of the research laboratory's focus on de novo variants. Subsequent phenotyping revealed variability in her manifestations. Although her metaphyseal abnormalities were more severe than in the original reported cohort with EFL1 variants, the bone marrow abnormalities were generally mild, and there was equivocal evidence for pancreatic insufficiency. Despite the limited number of reported patients, variants in EFL1 appear to cause a broader spectrum of symptoms that overlap with those seen in SDS. Our report adds to the evidence of EFL1 being associated with an SDS-like phenotype and provides information adding to our understanding of the phenotypic variability of this disorder. Our report also highlights the value of exome data reanalysis when a diagnosis is not initially apparent

Regulation of virulence gene expression resulting from Streptococcus pneumoniae and nontypeable Haemophilus influenzae interactions in chronic disease

Chronic rhinosinusitis (CRS) is a common inflammatory disease of the sinonasal cavity mediated, in part, by polymicrobial communities of bacteria. Recent molecular studies have confirmed the importance of Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi) in CRS. Here, we hypothesize that interaction between S. pneumoniae and NTHi mixed-species communities cause a change in bacterial virulence gene expression. We examined CRS as a model human disease to validate these polymicrobial interactions. Clinical strains of S. pneumoniae and NTHi were grown in mono- and coculture in a standard biofilm assay. Reverse transcriptase real-time PCR (RTqPCR) was used to measure gene expression of key virulence factors. To validate these results, we investigated the presence of the bacterial RNA transcripts in excised human tissue from patients with CRS. Consequences of physical or chemical interactions between microbes were also investigated. Transcription of NTHi type IV pili was only expressed in co-culture in vitro, and expression could be detected ex vivo in diseased tissue. S. pneumoniae pyruvate oxidase was up-regulated in co-culture, while pneumolysin and pneumococcal adherence factor A were down-regulated. These results were confirmed in excised human CRS tissue. Gene expression was differentially regulated by physical contact and secreted factors. Overall, these data suggest that interactions between H. influenzae and S. pneumoniae involve physical and chemical mechanisms that influence virulence gene expression of mixed-species biofilm communities present in chronically diseased human tissue. These results extend previous studies of population-level virulence and provide novel insight into the importance of S. pneumoniae and NTHi in CRS

An evaluation of surface meteorology and fluxes over the Iceland and Greenland Seas in ERA5 reanalysis: the impact of sea ice distribution

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Renfrew, I. A., Barrell, C., Elvidge, A. D., Brooke, J. K., Duscha, C., King, J. C., Kristiansen, J., Cope, T. L., Moore, G. W. K., Pickart, R. S., Reuder, J., Sandu, I., Sergeev, D., Terpstra, A., Vage, K., & Weiss, A. An evaluation of surface meteorology and fluxes over the Iceland and Greenland Seas in ERA5 reanalysis: the impact of sea ice distribution. Quarterly Journal of the Royal Meteorological Society, (2020): 1-22, doi:10.1002/qj.3941.The Iceland and Greenland Seas are a crucial region for the climate system, being the headwaters of the lower limb of the Atlantic Meridional Overturning Circulation. Investigating the atmosphere–ocean–ice processes in this region often necessitates the use of meteorological reanalyses—a representation of the atmospheric state based on the assimilation of observations into a numerical weather prediction system. Knowing the quality of reanalysis products is vital for their proper use. Here we evaluate the surface‐layer meteorology and surface turbulent fluxes in winter and spring for the latest reanalysis from the European Centre for Medium‐Range Weather Forecasts, i.e., ERA5. In situ observations from a meteorological buoy, a research vessel, and a research aircraft during the Iceland–Greenland Seas Project provide unparalleled coverage of this climatically important region. The observations are independent of ERA5. They allow a comprehensive evaluation of the surface meteorology and fluxes of these subpolar seas and, for the first time, a specific focus on the marginal ice zone. Over the ice‐free ocean, ERA5 generally compares well to the observations of surface‐layer meteorology and turbulent fluxes. However, over the marginal ice zone, the correspondence is noticeably less accurate: for example, the root‐mean‐square errors are significantly higher for surface temperature, wind speed, and surface sensible heat flux. The primary reason for the difference in reanalysis quality is an overly smooth sea‐ice distribution in the surface boundary conditions used in ERA5. Particularly over the marginal ice zone, unrepresented variability and uncertainties in how to parameterize surface exchange compromise the quality of the reanalyses. A parallel evaluation of higher‐resolution forecast fields from the Met Office's Unified Model corroborates these findings.This study was part of the Iceland Greenland Seas Project. Funding was from the NERC AFIS grant (NE/N009754/1), the ALERTNESS (Advanced models and weather prediction in the Arctic: enhanced capacity from observations and polar process representations) project (Research Council of Norway project number 280573), the Trond Mohn Foundation (BFS2016REK01), and the National Science Foundation grant OCE‐1558742. The Leosphere WindCube v2 and the Wavescan buoy are part of the OBLO (Offshore Boundary Layer Observatory) infrastructure funded by the Research Council of Norway (project number 227777)

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin