Relationships of Moral Distress among Interprofessional ICU Teams

Background: Moral distress is the psychological response to knowing the right action required by a healthcare professional but being unable to act upon the right course of action due to internal, external, and institutional constraints. Purpose: The study investigated: 1. the level of moral distress among interprofessional healthcare providers working in four ICUs of a single academic hospital as measured by the 21-item Moral Distress Scale-Revised (MDS-R), 2. the differences in moral distress among interprofessional healthcare providers based on demographic characteristics and rankings of clinical scenario on the MDS-R. Method: Descriptive, cross-sectional design using survey methodology. Outcomes: Significant differences in mean moral distress (F = 4.105, p = .001), moral distress frequency (F = 2.868, p = .016), and moral distress intensity (F = 4.341, p = .001) were found between professional roles. Significant differences in moral distress frequency among the ICUs (F = 3.871, p = .010) and differences in mean moral distress between levels of education (F= 5.849, p = .001) and years of ICU experience (F = 3.180, p = .009) was found. RNs (28.09) (±12.26) and respiratory therapists (28.45) (±11.92) reporting high moral distress also reported high moral distress frequency. Significant differences in moral distress intensity were found between professional roles with clergy reporting the highest and physicians reporting the lowest. Differences in moral distress between RNs (t (9.953) = 6.68, p = .000), clergy (t (14) = -2.44, p = .029), respiratory therapists (t (30) = -3.72, p = .001), and physicians (t (83) = -2.50, p = .014) were found. A significant relationship between moral distress scores and team dynamics (rs= .423, p = .000) and team communication (rs= .447, p = .000) was found. Conclusion: Low to moderate moral distress was found among all professional roles with significant differences seen between direct and indirect healthcare providers. Mean moral distress scores were highest in respiratory therapists and RNs compare to dieticians. Moral distress was highest in adult ICUs compared to pediatric ICUs

The Impact of Mindfulness-Based Stress Reduction Techniques on Nurse Burnout in an ICU

Practice Problem: Burnout among nurses has been linked to turnover, negative patient safety and quality outcomes, and higher costs for institutions. PICOT: The PICOT question that guided this project was, in ICU nurses (P), what was the impact of the use of MBSR techniques (I), versus the current state in which no MBSR techniques are practiced (C), on self-reported BO (O), over the course of eight weeks (T). Evidence: A total of 14 studies were identified in the literature that directly support the implementation of this project. Themes from the literature show that mindfulness-based stress reduction techniques such as meditation, yoga, and gratitude may reduce nurse burnout. Intervention: A variety of mindfulness-based stress reduction (MBSR) techniques were implemented including a pre-shift “loving kindness” meditation, a five minute “Lunch Break Yoga” practice, and a post-shift gratitude reflection. Outcome: Data demonstrated that 88.9% of the participants reported reduced levels of burnout. A paired t-test showed a statistically significant reduction in BO. Conclusion: The use of MBSR techniques may provide a method to reduce burnout, possibly improving retention and outcomes, reducing costs for institutions. Keywords: nurse burnout, burnout, mindfulness, mindfulness-based stress reductio

HERMDAA COMPARISON OF CADENCE AND CENTER OF MASS DISPLACEMENT BETWEEN HEALTHY AND RECENTLY INJURED RECREATIONAL RUNNERS

The purpose of this study was to compare running cadence and the vertical center of mass (CoM) displacement between healthy and recently injured runners. An existing database was queried for recreational runners injured within the prior six weeks with limitation to their running participation (N=32) who were then matched with healthy runners (N=64). Cadence, CoM displacement, and lower extremity joint excursion assessed with 3D videography at self-selected speed were compared between groups using analyses of variance. CoM displacement was significantly reduced in recently injured runners (8.26±1.25cm vs 8.94±1.17cm, p=0.01); no other differences were found. Findings suggest an adaptation to reduce joint forces due to pain rather than a risk factor for injury; as such, this finding be relevant to injury prevention and rehabilitation

The Influence of Yoga-Based Programs on Risk Profiles in Adults with Type 2 Diabetes Mellitus: A Systematic Review

There is growing evidence that yoga may offer a safe and cost-effective intervention for Type 2 Diabetes mellitus (DM 2). However, systematic reviews are lacking. This article critically reviews the published literature regarding the effects of yoga-based programs on physiologic and anthropometric risk profiles and related clinical outcomes in adults with DM 2. We performed a comprehensive literature search using four computerized English and Indian scientific databases. The search was restricted to original studies (1970–2006) that evaluated the metabolic and clinical effects of yoga in adults with DM 2. Studies targeting clinical populations with cardiovascular disorders that included adults with comorbid DM were also evaluated. Data were extracted regarding study design, setting, target population, intervention, comparison group or condition, outcome assessment, data analysis and presentation, follow-up, and key results, and the quality of each study was evaluated according to specific predetermined criteria. We identified 25 eligible studies, including 15 uncontrolled trials, 6 non-randomized controlled trials and 4 randomized controlled trials (RCTs). Overall, these studies suggest beneficial changes in several risk indices, including glucose tolerance and insulin sensitivity, lipid profiles, anthropometric characteristics, blood pressure, oxidative stress, coagulation profiles, sympathetic activation and pulmonary function, as well as improvement in specific clinical outcomes. Yoga may improve risk profiles in adults with DM 2, and may have promise for the prevention and management of cardiovascular complications in this population. However, the limitations characterizing most studies preclude drawing firm conclusions. Additional high-quality RCTs are needed to confirm and further elucidate the effects of standardized yoga programs in populations with DM 2

Regulation of mRNA Translation by Human Cytomegalovirus pTRS1

Human cytomegalovirus (HCMV) is a major public health burden. Acute infection during pregnancy can lead to congenital birth defects, and reactivation of a latent infection in immune compromised individuals can cause significant morbidity and mortality. HCMV does not encode its own ribosomes, and is therefore completely reliant on the host translation machinery for viral protein synthesis. HCMV also does not induce host translational shutoff upon infection, thus viral mRNAs must compete with cellular mRNAs to efficiently translate viral proteins. The HCMV protein TRS1 (pTRS1) plays an integral role in translation regulation during HCMV replication by antagonizing the antiviral kinase PKR. Activated PKR phosphorylates eIF2α, which causes an overall inhibition of protein synthesis that inhibits HCMV replication. pTRS1 also increases overall levels of protein synthesis and enhances the translation of reporter mRNAs in a PKR-independent manner, showing that pTRS1 regulates mRNA translation through multiple mechanisms. In this dissertation I sought to define the mechanisms used by pTRS1 to stimulate translation. In chapter 1 I show that pTRS1 inhibits PKR activation by binding to PKR and inhibiting PKR kinase activity. pTRS1 binds PKR residues that are conserved across eIF2α kinases, suggesting that pTRS1 can antagonize multiple eIF2α kinases. In chapter 2 I show that pTRS1 stimulates cap-independent translation. pTRS1 enhances the activity of both host and viral internal ribosome entry sites (IRESs) and stimulates translation of a circular mRNA reporter. These pTRS1 functions were independent of its ability to antagonize PKR, but dependent on its ability to bind double-stranded RNA. To understand how pTRS1 stimulates translation, in chapter 4 I identify ribosome-associated, cellular proteins that bind pTRS1. I found that pTRS1 interacts with active protein phosphatase 1 (PP1) catalytic subunits. Rather than affect PP1 catalytic activity, pTRS1 changes the complement of proteins that interact with the PP1 alpha catalytic subunit, possibly to regulate PP1 substrate specificity. Together these data further characterize the mechanisms used by pTRS1 to regulate mRNA translation and reveal how pTRS1 may contribute to the efficient translation of viral mRNAs during HCMV infection.Doctor of Philosoph

EFFECT OF LANDING SURFACE AND UPPER EXTREMITY CONSTRAINT ON BIOMECHANICS GRADED BY THE LANDING ERROR SCORING SYSTEM

The purpose of this study was to compare jump-landing biomechanics across 1) landing surface condition; and 2) upper extremity constraint condition as graded by the Landing Error Scoring System (LESS). Recreational athletes (N=40; 21M, 19F) performed three jump-landings with three surface (Grass (GS), Court (CS), and Tile (TS)) and upper extremity constraint conditions (unconstrained (UN), football (AF), and lacrosse stick (LS)). The jump-landings were recorded via 2D videography and graded using the LESS. No differences were observed by surface (GS=5.01±1.40; CS=4.83±1.31; TS=5.09±1.86, p=0.52) or constraint condition (UN=5.09±1.86; FB=4.76±1.65; LS=4.86±1.76; p=0.21). The results indicate that the LESS is a robust instrument biomechanical screening in different landing environments and with sports with different upper extremity equipment

Human Cytomegalovirus pTRS1 and pIRS1 Antagonize Protein Kinase R To Facilitate Virus Replication

ABSTRACT Human cytomegalovirus (HCMV) counteracts host defenses that otherwise act to limit viral protein synthesis. One such defense is the antiviral kinase protein kinase R (PKR), which inactivates the eukaryotic initiation factor 2 (eIF2) translation initiation factor upon binding to viral double-stranded RNAs. Previously, the viral TRS1 and IRS1 proteins were found to antagonize the antiviral kinase PKR outside the context of HCMV infection, and the expression of either pTRS1 or pIRS1 was shown to be necessary for HCMV replication. In this study, we found that expression of either pTRS1 or pIRS1 is necessary to prevent PKR activation during HCMV infection and that antagonism of PKR is critical for efficient viral replication. Consistent with a previous study, we observed decreased overall levels of protein synthesis, reduced viral protein expression, and diminished virus replication in the absence of both pTRS1 and pIRS1. In addition, both PKR and eIF2α were phosphorylated during infection when pTRS1 and pIRS1 were absent. We also found that expression of pTRS1 was both necessary and sufficient to prevent stress granule formation in response to eIF2α phosphorylation. Depletion of PKR prevented eIF2α phosphorylation, rescued HCMV replication and protein synthesis, and reversed the accumulation of stress granules in infected cells. Infection with an HCMV mutant lacking the pTRS1 PKR binding domain resulted in PKR activation, suggesting that pTRS1 inhibits PKR through a direct interaction. Together our results show that antagonism of PKR by HCMV pTRS1 and pIRS1 is critical for viral protein expression and efficient HCMV replication. IMPORTANCE To successfully replicate, viruses must counteract host defenses that limit viral protein synthesis. We have identified inhibition of the antiviral kinase PKR by the viral proteins TRS1 and IRS1 and shown that this is a critical step in HCMV replication. Our results suggest that inhibiting pTRS1 and pIRS1 function or restoring PKR activity during infection may be a successful strategy to limit HCMV disease

Mechanism of Protein Kinase R Inhibition by Human Cytomegalovirus pTRS1

ABSTRACT Double-stranded RNAs (dsRNA) produced during human cytomegalovirus (HCMV) infection activate the antiviral kinase protein kinase R (PKR), which potently inhibits virus replication. The HCMV pTRS1 and pIRS1 proteins antagonize PKR to promote HCMV protein synthesis and replication; however, the mechanism by which pTRS1 inhibits PKR is unclear. PKR activation occurs in a three-step cascade. First, binding to dsRNA triggers PKR homodimerizaton. PKR dimers then autophosphorylate, leading to a conformational shift that exposes the binding site for the PKR substrate eIF2α. Consistent with previous in vitro studies, we found that pTRS1 bound and inhibited PKR. pTRS1 binding to PKR was not mediated by an RNA intermediate, and mutations in the pTRS1 RNA binding domain did not affect PKR binding or inhibition. Rather, mutations that disrupted the pTRS1 interaction with PKR ablated the ability of pTRS1 to antagonize PKR activation by dsRNA. pTRS1 did not block PKR dimerization and could bind and inhibit a constitutively dimerized PKR kinase domain. In addition, pTRS1 binding to PKR inhibited PKR kinase activity. Single amino acid point mutations in the conserved eIF2α binding domain of PKR disrupted pTRS1 binding and rendered PKR resistant to inhibition by pTRS1. Consistent with a critical role for the conserved eIF2α contact site in PKR binding, pTRS1 bound an additional eIF2α kinase, heme-regulated inhibitor (HRI), and inhibited eIF2α phosphorylation in response to an HRI agonist. Together our data suggest that pTRS1 inhibits PKR by binding to conserved amino acids in the PKR eIF2α binding site and blocking PKR kinase activity. IMPORTANCE The antiviral kinase PKR plays a critical role in controlling HCMV replication. This study furthered our understanding of how HCMV evades inhibition by PKR and identified new strategies for how PKR activity might be restored during infection to limit HCMV disease

The state of OA: a large-scale analysis of the prevalence and impact of Open Access articles

Despite growing interest in Open Access (OA) to scholarly literature, there is an unmet need for large-scale, up-to-date, and reproducible studies assessing the prevalence and characteristics of OA. We address this need using oaDOI, an open online service that determines OA status for 67 million articles. We use three samples, each of 100,000 articles, to investigateOAin three populations: (1) all journal articles assigned a Crossref DOI, (2) recent journal articles indexed in Web of Science, and (3) articles viewed by users of Unpaywall, an open-source browser extension that lets users find OA articles using oaDOI. We estimate that at least 28% of the scholarly literature is OA (19M in total) and that this proportion is growing, driven particularly by growth in Gold and Hybrid. The most recent year analyzed (2015) also has the highest percentage of OA (45%). Because of this growth, and the fact that readers disproportionately access newer articles, we find that Unpaywall users encounter OA quite frequently: 47% of articles they view are OA. Notably, the most common mechanism for OA is not Gold, Green, or Hybrid OA, but rather an under-discussed category we dub Bronze: articles made freeto- read on the publisher website, without an explicit Open license. We also examine the citation impact of OA articles, corroborating the so-called open-access citation advantage: accounting for age and discipline, OA articles receive 18% more citations than average, an effect driven primarily by Green and Hybrid OA.Weencourage further research using the free oaDOI service, as a way to inform OA policy and practice

The Role of Adenovirus Serotype 5 E4 11k in the Relocalization of the Cellular P Body Proteins

Human adenoviruses are a useful tool to understand basic cellular biology in addition to viral infections. Historically, cellular splicing was first discovered in adenovirus, but other cellular processes, such as double-strand break repair and aggresome formation, have been further elucidated through adenoviral infection. The adenovirus protein E4 11k has been shown to disrupt cytoplasmic processing bodies (p bodies), which are not well-understood but are involved in mRNA metabolism. Several p body proteins were found to be reorganized in the cytoplasm with adenovirus serotype 5 (Ad5) able to cause the colocalization of these p body proteins with aggresomes. The p body protein Lsm1 has been found to colocalize with E4 11k in aggresomes, but Edc3 and Pat1b are two p body proteins that have not been as well-studied in adenovirus-infected cells. Cells were treated with cadmium chloride or infected with wild-type and mutant viruses before staining them to visualize the p body proteins and a marker for viral infection by confocal microscopy. We were able to determine that the presence of E4 11k was not necessary for relocalization of either Lsm1 or Edc3 to aggresomes, while Pat1b did not localize to aggresomes under any conditions tested. We wanted to characterize Pat1b relocalization further so we counted the number of Pat1b foci in mock-infected cells and then the virally-infected cells, and were able to determine that Ad5 E4 11k is necessary and sufficient to induce an increase in cytoplasmic Pat1b foci. We also determined that this increase in Pat1b foci appears to be serotype-specific when compared to Ad9 and Ad12 E4 11k protein. The lack of apparent change with Pat1b localization with Ad9 E4 11k expression was a novel finding that suggests there may be something unique about Pat1b and p body localization