Search

Introduction: In January 2020, a small, private school of nursing in a university in the pacific northwest, established the Initiative for Vital Practice (I4VP). The I4VP's primary goal was to create a sustainable pathway for increasing vital practice through increasing resiliency and self-care practices., Objectives: The ensuing pathway's objectives were to, (1) take previously identified factors related to perceived stress related to workloads, impacts on professional quality of life and psychosocial exposures during the COVID-19 pandemic; and (2) develop and pilot test a wellness intervention (i.e., wellness pods) for faculty and staff to build community and find new ways to enhance well-being through peer support., Methods: Five focused Wellness Pods were developed on Microsoft Teams platform using the individual channels: (1) stress and mind-body exploration pod; (2) mindfulness in healthcare pod; (3) healing relationship pod; (4) environmental pod; and (5) physical activity pod. Faculty and staff self-selected into a Wellness Pod that interested them. The Wellness Pods met weekly in person over a period of two months. Quantitative and qualitative data was collected via cross-sectional surveys including: four sociodemographic items, one item on current stress level, one write-in item on current stress management at work, two write-in items focused on the cognitive reasoning for participation, the 7-item subjective vitality scale focused individual difference, the 7-item subjective vitality scale focused on the state level, the 10-item perceived stress scale, and one item ranking which wellness pod the individual wanted to participate in. There was one trained facilitator for the overall Wellness Pods operations and communication., Results: The average score on the perceived stress scale was 22.3 (SD = 3.5), indicating moderate levels of perceived stress. The average score on the individual difference vitality score was 26.5 (SD = 7.6), whereas the state level vitality score was 21.4 (SD = 9.98), indicating moderate levels of subjective vitality. Two categories: stress management and wellness pods, were identified through content analysis., Conclusions: Through pilot testing, this project demonstrated feasibility for future wellness pods interventions for faculty and staff at schools of nursing. Future research is needed to evaluate the effectiveness of the wellness pods intervention.

Background: Support for diverse nursing students needs to be built into existing peer-mentoring programs to foster success for all students., Method: Students were intentionally matched in a peer-mentoring program, BUDDY-UP, on several factors, which included students' race and ethnicity (Black, Indigenous, and People of Color [BIPOC]) and gender, and whether they were first-generation., Results: Mentors and mentees expressed satisfaction and derived benefits from the intentionally matched mentoring program. Participant comments demonstrated that these are not just extra supports but instead are fundamental to their essential everyday needs and ability to be successful both academically and socially., Conclusion: Incorporating support for all students needs to be a foundational aspect in the development of peer-mentoring programs to support the ability for all students to be successful in nursing education. [ J Nurs Educ . 2022;61(11):633-635.] .

The unique health care needs of diverse individuals and communities are complex. To meet these needs, healthcare professionals are being called upon to alter traditional ways of thinking, perceiving, and acting in order to create more inclusive environments. Research shows that using mindsight, a process that increases both insight and empathy, can enhance an individual's mind-body-environment connection, increase self-awareness, and promote the development of cultural humility. This paper will discuss the current perspectives on the mind/body/environment connection from a Western lens that may impact the enactment of cultural humility for healthcare providers. Two evidence-based approaches, yoga and forest therapy, are recommended as effective intervention tools in fostering mindsight and cultural humility. Blending traditional cognitive learning with techniques anchored in the physical body may hold promise in supporting the development of mindsight and cultural humility in healthcare education and practice.

Burnout, compassion fatigue, and perceived stress among undergraduate nursing students are significant factors leading to a poorer quality of life, decreased job satisfaction, and adversely impact patient outcomes. Burnout among undergraduate nursing students is a critical individual and workforce issue with contributing factors including a relentless schedule, academically challenging and rigorous programs, pressure to perform, and the completion of clinical hours caring for patients. This paper describes our feasibility study of a nature-based intervention (NBI) to reduce perceived stress and quality of life as it relates to burnout, and compassion fatigue. Quantitative data was collected through demographics, surveys, and electronic sensor data. The project's aim was to determine the feasibility of NBI monitored by NatureDose TM to decrease perceived stress burnout and compassion fatigue among undergraduate nursing students.

This manuscript offers findings from a pilot project which prepares nursing students for embodied professional practice through the lens of ethics. Four undergraduate nursing students were mentored by two nursing faculty in the Dundon-Berchtold Institute Faculty Fellowship Program in the Application of Ethics through an exploration on the ethics of embodiment using an arts pedagogy across one academic year. Inspired by the intersection of nature and health, this project explores the impact of an arts-integrated pedagogy on the human body. The findings from this project provide a natural first step for nursing students to consider multiple interpretations of the human body and to facilitate the students' development of an embodied ethical practice that is perceptive, empathic, and attuned to themselves as natural beings as well as diverse individuals and populations. The findings from this pilot project presents a pivotal opportunity to guide future nursing curricular development toward holistic, nature-inspired, and mindful-based interventions in order to increase resilience, decrease risk factors of compassion fatigue and burnout, and support nursing students to develop strength-based skills to use in their professional nursing practice.

Tetanus vaccination is of major importance for public health in most countries in the world. The World Health Organization indicated that 15,000 tetanus cases were reported in 2018 (Organization, World Health, 2019). Currently, vaccine manufacturers use tetanus toxin produced by Clostridium tetani fermentation in complex media. The complex components, commonly derived from animal sources, introduce potential variability in cultures. To achieve replicable fermentation and to avoid toxic or allergic reactions from animal-source compounds, several studies have tried to switch from complex to chemically defined media without affecting toxin titers. The present review introduces the current knowledge on i) C. tetani strain diversity, whole-genome sequences and metabolic networks; ii) toxin regulation and synthesis; and iii) culture media, cultivation processes and growth requirements. We critically reviewed the reported data on metabolism in C. tetani and completed comparative genomic and proteomic analyses with other Clostridia species. We integrated genomic data based on whole-genome sequence annotation, supplemented with cofactor specificities determined by protein sequence identity, in a new map of C. tetani central metabolism. This is the first data review that integrates insights from omics experiments on C. tetani. The overview of C. tetani physiology described here could provide support for the design of new chemically defined media devoid of complex sources for toxin production., (Copyright © 2021. Published by Elsevier Inc.)

While blocking the renin angiotensin aldosterone system (RAAS) has been the main therapeutic strategy to control diabetic kidney disease (DKD) for many years, 25-30% of diabetic patients still develop the disease. In the present work we adopted a systems biology strategy to analyze glomerular protein signatures to identify drugs with potential therapeutic properties in DKD acting through a RAAS-independent mechanism. Glomeruli were isolated from wild type and type 1 diabetic (Ins2Akita) mice treated or not with the angiotensin-converting enzyme inhibitor (ACEi) ramipril. Ramipril efficiently reduced the urinary albumin/creatine ratio (ACR) of Ins2Akita mice without modifying DKD-associated renal-injuries. Large scale quantitative proteomics was used to identify the DKD-associated glomerular proteins (DKD-GPs) that were ramipril-insensitive (RI-DKD-GPs). The raw data are publicly available via ProteomeXchange with identifier PXD018728. We then applied an in silico drug repurposing approach using a pattern-matching algorithm (Connectivity Mapping) to compare the RI-DKD-GPs's signature with a collection of thousands of transcriptional signatures of bioactive compounds. The sesquiterpene lactone parthenolide was identified as one of the top compounds predicted to reverse the RI-DKD-GPs's signature. Oral treatment of 2 months old Ins2Akita mice with dimethylaminoparthenolide (DMAPT, a water-soluble analogue of parthenolide) for two months at 10 mg/kg/d by gavage significantly reduced urinary ACR. However, in contrast to ramipril, DMAPT also significantly reduced glomerulosclerosis and tubulointerstitial fibrosis. Using a system biology approach, we identified DMAPT, as a compound with a potential add-on value to standard-of-care ACEi-treatment in DKD.

A bioreactor was designed to provide high gas mass transfer to reach cell and product titres in the g L -1 level from CO 2 for realistic, laboratory scale, engineered autotrophic strain evaluation. The design was based on independent CO 2 , H 2 and air inputs and the ability to operate at high pressures. The bioreactor configuration and cultivation strategy enabled growth of Cupriavidus necator strains for long periods, to reach over 3 g L -1 dry cell weight. No negative impact of the high pressure was observed on viability of the strains up to more than 4 bar overpressure. The cultivation was then carried out using an engineered isopropanol producing strain; in this case, 3.5 g L -1 isopropanol was obtained from CO 2 as the sole carbon source. This is the first reported demonstration of a successful production from engineered bacteria of product in the g L -1 range on CO 2 , raising the prospect of future development of CO 2 -based bioprocesses., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

The proteasome controls a multitude of cellular processes through protein degradation and has been identified as a therapeutic target in oncology. However, our understanding of its function and the development of specific modulators are hampered by the lack of a straightforward method to determine the overall proteasome status in biological samples. Here, we present a method to determine the absolute quantity and stoichiometry of ubiquitous and tissue-specific human 20S proteasome subtypes based on a robust, absolute SILAC-based multiplexed LC-Selected Reaction Monitoring (SRM) quantitative mass spectrometry assay with high precision, accuracy, and sensitivity. The method was initially optimized and validated by comparison with a reference ELISA assay and by analyzing the dynamics of catalytic subunits in HeLa cells following IFNγ-treatment and in range of human tissues. It was then successfully applied to reveal IFNγ- and O 2 -dependent variations of proteasome status during primary culture of Adipose-derived-mesenchymal Stromal/Stem Cells (ADSCs). The results show the critical importance of controlling the culture conditions during cell expansion for future therapeutic use in humans. We hypothesize that a shift from the standard proteasome to the immunoproteasome could serve as a predictor of immunosuppressive and differentiation capacities of ADSCs and, consequently, that quality control should include proteasomal quantification in addition to examining other essential cell parameters. The method presented also provides a new powerful tool to conduct more individualized protocols in cancer or inflammatory diseases where selective inhibition of the immunoproteasome has been shown to reduce side effects., (© 2019 Menneteau et al.)

The question whether and which nonhuman peptides or proteins are present in human milk was raised many decades ago. However, due to cross-reactivity or nonspecific antibody recognition, the accuracy of detection by immunochemical methods has been a concern. Additionally, the relative low-abundance of nonhuman peptides/proteins in the complex milk sample makes them a challenging target to detect. Here, by deep proteome profiling, we detected several nonhuman peptides, which could be grouped as nonhuman proteins. We next estimated their concentration in human milk by combining data-dependent shotgun proteomics and parallel reaction monitoring. First, we fractionated human milk at the protein level and were able to detect 1577 human proteins. Additionally, we identified 109 nonhuman peptides, of which 71 were grouped into 36 nonhuman proteins. In the next step, we targeted 37 nonhuman peptides and nine of them could be repeatedly quantified in human milk samples. Peptides/proteins originating from bovine milk products were the dominant nonhuman proteins observed, notably bovine caseins (α-S1-, α-S2-, β-, κ-caseins) and β-lactoglobulin. The method we present here can be expanded to investigate more about nonhuman peptides and proteins in human milk and give a better understanding of how human milk plays a role in allergy prevention.

Compelling evidence suggests that Cold Atmospheric Pressure Plasma (CAPP) has potential as a new cancer therapy. However, knowledge about cellular signaling events and toxicity subsequent to plasma treatment is still poorly documented. The aim of this study was to focus on the interaction between 3 different types of plasma (He, He-O 2 , He-N 2 ) and human epithelial cell lines to gain better insight into plasma-cell interaction. We provide evidence that reactive oxygen and nitrogen species (RONS) are inducing cell death by apoptosis and that the proteasome, a major intracellular proteolytic system which is important for tumor cell growth and survival, is a target of (He or He-N 2 ) CAPP. However, RONS are not the only actors involved in cell death; electric field and charged particles could play a significant role especially for He-O 2 CAPP. By differential label-free quantitative proteomic analysis we found that CAPP triggers antioxidant and cellular defense but is also affecting extracellular matrix in keratinocytes. Moreover, we found that malignant cells are more resistant to CAPP treatment than normal cells. Taken together, our findings provide insight into potential mechanisms of CAPP-induced proteasome inactivation and the cellular consequences of these events.

Hypothesis-driven MS-based targeted proteomics has gained great popularity in a relatively short timespan. Next to the widely established selected reaction monitoring (SRM) workflow, data-independent acquisition (DIA), also referred to as sequential window acquisition of all theoretical spectra (SWATH) was introduced as a high-throughput targeted proteomics method. DIA facilitates increased proteome coverage, however, does not yet reach the sensitivity obtained with SRM. Therefore, a well-informed method selection is crucial for designing a successful targeted proteomics experiment. This is especially the case when targeting less conventional peptides such as those that contain PTMs, as these peptides do not always adhere to the optimal fragmentation considerations for targeted assays. Here, we provide insight into the performance of DIA, SRM, and MRM cubed (MRM(3) ) in the analysis of phosphorylation dynamics throughout the phosphoinositide 3-kinase mechanistic target of rapamycin (PI3K-mTOR) and mitogen-activated protein kinase (MAPK) signaling network. We observe indeed that DIA is less sensitive when compared to SRM, however demonstrates increased flexibility, by postanalysis selection of alternative phosphopeptide precursors. Additionally, we demonstrate the added benefit of MRM(3) , allowing the quantification of two poorly accessible phosphosites. In total, targeted proteomics enabled the quantification of 42 PI3K-mTOR and MAPK phosphosites, gaining a so far unachieved in-depth view mTOR signaling events linked to tyrosine kinase inhibitor resistance in non-small cell lung cancer., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In the framework of the C-HPP, our Franco-Swiss consortium has adopted chromosomes 2 and 14, coding for a total of 382 missing proteins (proteins for which evidence is lacking at protein level). Over the last 4 years, the French proteomics infrastructure has collected high-quality data sets from 40 human samples, including a series of rarely studied cell lines, tissue types, and sample preparations. Here we described a step-by-step strategy based on the use of bioinformatics screening and subsequent mass spectrometry (MS)-based validation to identify what were up to now missing proteins in these data sets. Screening database search results (85,326 dat files) identified 58 of the missing proteins (36 on chromosome 2 and 22 on chromosome 14) by 83 unique peptides following the latest release of neXtProt (2014-09-19). PSMs corresponding to these peptides were thoroughly examined by applying two different MS-based criteria: peptide-level false discovery rate calculation and expert PSM quality assessment. Synthetic peptides were then produced and used to generate reference MS/MS spectra. A spectral similarity score was then calculated for each pair of reference-endogenous spectra and used as a third criterion for missing protein validation. Finally, LC-SRM assays were developed to target proteotypic peptides from four of the missing proteins detected in tissue/cell samples, which were still available and for which sample preparation could be reproduced. These LC-SRM assays unambiguously detected the endogenous unique peptide for three of the proteins. For two of these, identification was confirmed by additional proteotypic peptides. We concluded that of the initial set of 58 proteins detected by the bioinformatics screen, the consecutive MS-based validation criteria led to propose the identification of 13 of these proteins (8 on chromosome 2 and 5 on chromosome 14) that passed at least two of the three MS-based criteria. Thus, a rigorous step-by-step approach combining bioinformatics screening and MS-based validation assays is particularly suitable to obtain protein-level evidence for proteins previously considered as missing. All MS/MS data have been deposited in ProteomeXchange under identifier PXD002131.

In eukaryotic cells, intracellular protein breakdown is mainly performed by the ubiquitin-proteasome system. Proteasomes are supramolecular protein complexes formed by the association of multiple sub-complexes and interacting proteins. Therefore, they exhibit a very high heterogeneity whose function is still not well understood. Here, using a newly developed method based on the combination of affinity purification and protein correlation profiling associated with high-resolution mass spectrometry, we comprehensively characterized proteasome heterogeneity and identified previously unknown preferential associations within proteasome sub-complexes. In particular, we showed for the first time that the two main proteasome subtypes, standard proteasome and immunoproteasome, interact with a different subset of important regulators. This trend was observed in very diverse human cell types and was confirmed by changing the relative proportions of both 20S proteasome forms using interferon-γ. The new method developed here constitutes an innovative and powerful strategy that could be broadly applied for unraveling the dynamic and heterogeneous nature of other biologically relevant supramolecular protein complexes., (© 2015 The Authors. Published under the terms of the CC BY 4.0 license.)

Obstructive nephropathy is a frequently encountered situation in newborns. In previous studies, the urinary peptidome has been analyzed for the identification of clinically useful biomarkers of obstructive nephropathy. However, the urinary proteome has not been explored yet and should allow additional insight into the pathophysiology of the disease. We have analyzed the urinary proteome of newborns (n = 5/group) with obstructive nephropathy using label free quantitative nanoLC-MS/MS allowing the identification and quantification of 970 urinary proteins. We next focused on proteins exclusively regulated in severe obstructive nephropathy and identified Arginase 1 as a potential candidate molecule involved in the development of obstructive nephropathy, located at the crossroad of pro- and antifibrotic pathways. The reduced urinary abundance of Arginase 1 in obstructive nephropathy was verified in independent clinical samples using both Western blot and MRM analysis. These data were confirmed in situ in kidneys obtained from a mouse obstructive nephropathy model. In addition, we also observed increased expression of Arginase 2 and increased total arginase activity in obstructed mouse kidneys. mRNA expression analysis of the related arginase pathways indicated that the pro-fibrotic arginase-related pathway is activated during obstructive nephropathy. Taken together we have identified a new actor in the development of obstructive nephropathy in newborns using quantitative urinary proteomics and shown its involvement in an in vivo model of disease. The present study demonstrates the relevance of such a quantitative urinary proteomics approach with clinical samples for a better understanding of the pathophysiology and for the discovery of potential therapeutic targets., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

Home care workers are a priority population for ergonomic assessment and intervention, but research on caregivers' exposures to hazards is limited. The current project evaluated the reliability and validity of an ergonomic self-assessment tool called Home Care STAT (Safety Task Assessment Tool). Participants (N = 23) completed a background survey followed by 10-14 days of self-monitoring with the STAT. Results showed that the most frequent task was house cleaning, and that participants regularly performed dangerous manual client moving and transferring tasks. Researcher in-home observations of 14 workers (duration ≤ 2 h) demonstrated that workers' self-assessments were moderately reliable. Correlational and multi-level analyses of daily self-assessment data revealed that several task exposures were significantly related to daily fatigue and/or pain. Other associations have implications for Total Worker Health™; for example, daily stress was positively associated with both pain and consumption of high calorie snacks. Findings support the STAT as a reliable and potentially valid tool for measuring home care workers' exposures to physically demanding tasks., (Copyright © 2014 Elsevier Ltd and The Ergonomics Society. All rights reserved.)

The proteasome is the main proteolytic system involved in intracellular proteins homeostasis in eukaryotes. Although the structure of proteasome complexes has been well characterized, the distribution of its activators and associated proteins are less studied. Here, we determine the composition and the stoichiometry of proteasome complexes and their associated proteins in a wide range of human cell lines using a one-step affinity purification method and a label-free quantitative proteomic approach. We show that proteasome complexes are highly dynamic protein assemblies, the activity of which being regulated at different levels by variations in the stoichiometry of bound regulators, in the composition of catalytic subunits and associated proteins, and in the rate of the 20S catalytic core complex assembly.

Faculty members are expected to integrate content about older adults into undergraduate curricula. Although numerous gerontological education resources exist on the Internet, educators often lack awareness of these resources or the time to explore them. We describe a project that used a peer-review process to organize resources into a searchable, online catalog that includes suggestions for using the content in different courses (http://www.ohsu.edu/son/ecleps). Implications are discussed for developing and maintaining the interactive catalog of Web-based instructional resources.

Background & Aims: Glucose is absorbed into intestine cells via the sodium glucose transporter 1 (SGLT-1) and glucose transporter 2 (GLUT2); various peptides and hormones control this process. Apelin is a peptide that regulates glucose homeostasis and is produced by proximal digestive cells; we studied whether glucose modulates apelin secretion by enterocytes and the effects of apelin on intestinal glucose absorption., Methods: We characterized glucose-related luminal apelin secretion in vivo and ex vivo by mass spectroscopy and immunologic techniques. The effects of apelin on (14)C-labeled glucose transport were determined in jejunal loops and in mice following apelin gavage. We determined levels of GLUT2 and SGLT-1 proteins and phosphorylation of AMPKα2 by immunoblotting. The net effect of apelin on intestinal glucose transepithelial transport was determined in mice., Results: Glucose stimulated luminal secretion of the pyroglutaminated apelin-13 isoform ([Pyr-1]-apelin-13) in the small intestine of mice. Apelin increased specific glucose flux through the gastric epithelial barrier in jejunal loops and in vivo following oral glucose administration. Conversely, pharmacologic apelin blockade in the intestine reduced the increased glycemia that occurs following oral glucose administration. Apelin activity was associated with phosphorylation of AMPKα2 and a rapid increase of the GLUT2/SGLT-1 protein ratio in the brush border membrane., Conclusions: Glucose amplifies its own transport from the intestinal lumen to the bloodstream by increasing luminal apelin secretion. In the lumen, active apelin regulates carbohydrate flux through enterocytes by promoting AMPKα2 phosphorylation and modifying the ratio of SGLT-1:GLUT2. The glucose-apelin cycle might be pharmacologically handled to regulate glucose absorption and assess better control of glucose homeostasis., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

This project extends research on hazardous exposures and injuries among home care workers. Historical data from Oregon home care workers were analyzed to identify the most common lost time injuries and contributing factors, and 7 focus groups were conducted with workers (n = 53) to gather data on demographics, health, and perceptions of occupational hazards. Results indicate that workers are at particular risk for back, knee, and shoulder injuries during client and material moving tasks and that workers' self-reported task exposures and risk perceptions are highly aligned with injury data.