Family Presence During Resuscitation of Adults: The Impact of an Online Learning Module on Critical Care Nurses\u27 Perception and Self-Confidence

Family presence during resuscitation (FPDR) involves offering family members the option to remain with their loved one who is undergoing life-saving measures. FPDR has been shown to enhance comfort and facilitate grieving, and 90% to 100% of patients and family members support it as an option. However, critical care nurses are not fully supportive of FPDR and approximately only one-third implement it in their care of patients. The perceived risks of FPDR are cited as a primary reason for lack of support and implementation. Yet, the perceived risks have not been proven, while the benefits have been established in research. This demonstrates the importance of education to improve critical care nurses\u27 perception of FPDR. Few studies have investigated FPDR education with nurses. The few that exist have shown promise in improving perception, and also self-confidence which has been shown to influences nurses\u27 FPDR implementation. Several gaps in the FPDR educational research have been identified; including use of measurement scales without established validity or reliability, restricted sample recruitment focused primarily on emergency department nurses despite the fact 45% of in-hospital resuscitation events occur in critical care settings, and methodological limitations such as the absence of a control group. Additionally, no research has yet evaluated the potential impact of online learning despite its capability of reaching larger numbers of nurses. Therefore, the purpose of this quasi-experimental study was to evaluate the impact of an online learning module on critical care nurses\u27 perception and self-confidence for FPDR of adult patients. The frameworks utilized were Change Theory and Social Cognitive Theory to explain the choice of dependent variables and aid in the design of the FPDR online learning module as the independent variable. A two-group, quasi-experimental, pre- and post-test design was used. The sample consisted of critical care nurses (N = 74) recruited through online study advertisements facilitated by the American Association of Critical-Care Nurses (AACN). Subjects were randomly assigned to either the intervention group who received the FPDR online learning module or to the control group who received online learning about recent changes in resuscitative care. Established measurement scales were used to evaluate perception and self-confidence in this repeated-measures study. Data was collected online for four weeks and the two-factor, mixed-model factorial ANOVA was used for data analysis. Major findings demonstrated the FPDR online learning module was effective at improving critical care nurses\u27 perception and self-confidence for FPDR. Mean scores in the intervention group increased significantly for both perception and self-confidence (p \u3c .0005), while scores did not change significantly for the control group. Study results indicate online learning can improve critical care nurses\u27 perception and self-confidence for FPDR and further strengthen the body of scientific evidence on FPDR education

The Application of FAST-NMR for the Identification of Novel Drug Discovery Targets

The continued success of genome sequencing projects has resulted in a wealth of information, but 40-50% of identified genes correspond to hypothetical proteins or proteins of unknown function. The Functional Annotation Screening Technology by NMR (FAST-NMR) screen was developed to assign a biological function for these unannotated proteins with a structure solved by the Protein Structure Initiative. FAST-NMR is based on the premise that a biological function can be described by a similarity in binding sites and ligand interactions with proteins of known function. The resulting co-structure and functional assignment may provide a starting point for a drug discovery effort

Using Databases and Computational Techniques to Infer the Function of Novel Proteins

The Human Genome Project and similar efforts have resulted in the identification of an abundance of novel proteins. There is a need to expedite the process of assigning function to novel proteins. Nuclear magnetic resonance (NMR) spectroscopy can be used to infer a general biological function for a protein of unknown function by identifying compounds that preferentially bind the protein and comparing these results against proteins with defined structure and function. The Functional NMR screen generates hundreds of data sets and a manual analysis of these data sets is laborious and time- consuming. It is hypothesized that several sub-tasks of the Functional NMR can be automated successfully using an integrated database and data analysis system. Our database system integrates NMR data collection, processing, analysis, and data archiving into a unified user interface. An NMR spectra comparison algorithm is designed and implemented to compare NMR data in the presence and absence of a protein to ascertain if any compound-protein binding occurred

Individual and Collective Contributions of Chaperoning and Degradation to Protein Homeostasis in E. coli

SummaryThe folding fate of a protein in vivo is determined by the interplay between a protein’s folding energy landscape and the actions of the proteostasis network, including molecular chaperones and degradation enzymes. The mechanisms of individual components of the E. coli proteostasis network have been studied extensively, but much less is known about how they function as a system. We used an integrated experimental and computational approach to quantitatively analyze the folding outcomes (native folding versus aggregation versus degradation) of three test proteins biosynthesized in E. coli under a variety of conditions. Overexpression of the entire proteostasis network benefited all three test proteins, but the effect of upregulating individual chaperones or the major degradation enzyme, Lon, varied for proteins with different biophysical properties. In sum, the impact of the E. coli proteostasis network is a consequence of concerted action by the Hsp70 system (DnaK/DnaJ/GrpE), the Hsp60 system (GroEL/GroES), and Lon

Predictive model of response to tafamidis in hereditary ATTR polyneuropathy

BACKGROUNDThe hereditary transthyretin (TTR) amyloidoses are a group of diseases for which several disease-modifying treatments are now available. Long-term effectiveness of these therapies is not yet fully known. Moreover, the existence of alternative therapies has resulted in an urgent need to identify patient characteristics that predict response to each therapy.METHODSWe carried out a retrospective cohort study of 210 patients with hereditary TTR amyloidosis treated with the kinetic stabilizer tafamidis (20 mg qd). These patients were followed for a period of 18-66 months, after which they were classified by an expert as responders, partial responders, or nonresponders. Correlations between baseline demographic and clinical characteristics, as well as plasma biomarkers and response to therapy, were investigated.RESULTS34% of patients exhibited an almost complete arrest of disease progression (classified by an expert as responders); 36% had a partial to complete arrest in progression of some but not all disease components (partial responders); whereas the remaining 30% continued progressing despite therapy (nonresponders). We determined that disease severity, sex, and native TTR concentration at the outset of treatment were the most relevant predictors of response to tafamidis. Plasma tafamidis concentration after 12 months of therapy was also a predictor of response for male patients. Using these variables, we built a model to predict responsiveness to tafamidis.CONCLUSIONOur study indicates long-term effectiveness for tafamidis, a kinetic stabilizer approved for the treatment of hereditary TTR amyloidosis. Moreover, we created a predictive model that can be potentially used in the clinical setting to inform patients and clinicians in their therapeutic decisions.info:eu-repo/semantics/publishedVersio

Clarifying assumptions in age-period-cohort analyses and validating results

Background Age-period-cohort (APC) models are often used to decompose health trends into period- and cohort-based sources, but their use in epidemiology and population sciences remains contentious. Central to the contention are researchers&rsquo; failures to 1) clearly state their analytic assumptions and/or 2) thoroughly evaluate model results. These failures often produce varying conclusions across APC studies and generate confusion about APC methods. Consequently, scholarly exchanges about APC methods usually result in strong disagreements that rarely offer practical advice to users or readers of APC methods. Methods We use research guidelines to help practitioners of APC methods articulate their analytic assumptions and validate their results. To demonstrate the usefulness of the guidelines, we apply them to a 2015 American Journal of Epidemiology study about trends in black-white differences in U.S. heart disease mortality. Results The application of the guidelines highlights two important findings. On the one hand, some APC methods produce inconsistent results that are highly sensitive to researcher manipulation. On the other hand, other APC methods estimate results that are robust to researcher manipulation and consistent across APC models. Conclusions The exercise shows the simplicity and effectiveness of the guidelines in resolving disagreements over APC results. The cautious use of APC models can generate results that are consistent across methods and robust to researcher manipulation. If followed, the guidelines can likely reduce the chance of publishing variable and conflicting results across APC studies. </div

CD4 T cell help prevents CD8 T cell exhaustion and promotes control of Mycobacterium tuberculosis infection [preprint]

CD4 T cells are essential for immunity to tuberculosis because they produce cytokines including interferon-γ. Whether CD4 T cells act as “helper” cells to promote optimal CD8 T cell responses during Mycobacterium tuberculosis is unknown. Using two independent models, we show that CD4 T cell help enhances CD8 effector functions and prevents CD8 T cell exhaustion. We demonstrate synergy between CD4 and CD8 T cells in promoting the survival of infected mice. Purified helped, but not helpless, CD8 T cells efficiently restrict intracellular bacterial growth in vitro. Thus, CD4 T cell help plays an essential role in generating protective CD8 T cell responses against M. tuberculosis infection in vitro and in vivo. We infer vaccines that elicit both CD4 and CD8 T cells are more likely to be successful than vaccines that elicit only CD4 or CD8 T cells

Multiple Novel Signals Mediate Thyroid Hormone Receptor Nuclear Import and Export

Thyroid hormone receptor (TR) is a member of the nuclear receptor superfamily that shuttles between the cytosol and nucleus. The fine balance between nuclear import and export of TR has emerged as a critical control point for modulating thyroid hormone-responsive gene expression; however, sequence motifs of TR that mediate shuttling are not fully defined. Here, we characterized multiple signals that direct TR shuttling. Along with the known nuclear localization signal in the hinge domain, we identified a novel nuclear localization signal in the A/B domain of thyroid hormone receptor a1 that is absent in thyroid hormone receptor B1 and inactive in the oncoprotein v-ErbA. Our prior studies showed that thyroid hormone receptor a1 exits the nucleus through two pathways, one dependent on the export factor CRM1 and the other CRM1-independent. Here, we identified three novel CRM1-independent nuclear export signal (NES) motifs in the ligand-binding domain as follows: a highly conserved NES in helix 12 (NES-H12) and two additional NES sequences spanning helix 3 and helix 6, respectively. Mutations predicted to disrupt the a-helical structure resulted in a significant decrease in NES-H12 activity. The high degree of conservation of helix 12 suggests that this region may function as a key NES in other nuclear receptors. Furthermore, our mutagenesis studies on NES-H12 suggest that altered shuttling of thyroid hormone receptor B1 may be a contributing factor in resistance to thyroid hormone syndrome. Taken together, our findings provide a detailed mechanistic understanding of the multiple signals that work together to regulate TR shuttling and transcriptional activity, and they provide important insights into nuclear receptor function in genera

\u3csup\u3e1\u3c/sup\u3eH, \u3csup\u3e13\u3c/sup\u3eC, and \u3csup\u3e15\u3c/sup\u3eN NMR assignments for the \u3ci\u3eBacillus subtilis\u3c/i\u3e yndB START domain

The steroidogenic acute regulatory-related lipid transfer (START) domain is found in both eukaryotes and prokaryotes, with putative functions including signal transduction, transcriptional regulation, GTPase activation and thioester hydrolysis. Here we report the near complete 1H, 15N and 13C backbone and side chain NMR resonance assignments for the Bacillus subtilis START domain protein yndB

Enhanced Aromatic Sequons Increase Oligosaccharyltransferase Glycosylation Efficiency and Glycan Homogeneity

SummaryN-Glycosylation plays an important role in protein folding and function. Previous studies demonstrate that a phenylalanine residue introduced at the n-2 position relative to an Asn-Xxx-Thr/Ser N-glycosylation sequon increases the glycan occupancy of the sequon in insect cells. Here, we show that any aromatic residue at n-2 increases glycan occupancy in human cells and that this effect is dependent upon oligosaccharyltransferase substrate preferences rather than differences in other cellular processing events such as degradation or trafficking. Moreover, aromatic residues at n-2 alter glycan processing in the Golgi, producing proteins with less complex N-glycan structures. These results demonstrate that manipulating the sequence space surrounding N-glycosylation sequons is useful both for controlling glycosylation efficiency, thus enhancing glycan occupancy, and for influencing the N-glycan structures produced