An evaluation of a pilot of daily testing of SARS-CoV-2 contacts in acute hospital and ambulance trusts in England.

OBJECTIVES: Healthcare worker (HCW) SARS-CoV-2 contacts in England have been required to quarantine, creating staff shortages. We piloted daily contact testing (DCT) to assess its feasibility as an alternative. STUDY DESIGN: Observational service evaluation. METHODS: We conducted an observational service evaluation of 7-day DCT using antigen lateral flow devices (LFDs) at four acute hospital trusts and one ambulance trust in England. Mixed methods were used, using aggregate and individual-level test monitoring data, semi-structured interviews, and a survey of eligible contacts. RESULTS: In total, 138 HCWs were identified as contacts of a confirmed SARS-CoV-2 case. Of these, 111 (80%) consented to daily LFD testing, of whom 82 (74%) completed the required programme without interruption and 12 (11%) completed with interruption. Fifty-eight participants (52%) and two non-participants (7.4%) completed the survey. In total, 28 interviews were conducted with participants, site and infection control leads, and union representatives. One participant tested positive on LFD and polymerase chain reaction (PCR) test. Three participants tested positive on PCR but not LFD. DCT was well-accepted by trusts and staff. Participants reported no relaxation of their infection prevention and control behaviours. No incidents of transmission were detected. An estimated 729 potential days of work absence were averted. CONCLUSIONS: DCT can be acceptably operated in a healthcare setting, averting quarantine-related work absences in HCW SARS-CoV-2 contacts.

Implementation of Safe Patient Handling in the U.S. Veterans Health System: A Qualitative Study of Internal Facilitators' Perceptions.

BACKGROUND: Although the literature has noted the positive effects of facilitation in implementation research, little is known about what facilitators do or how they increase adoption of a program. The purpose of this study was to understand internal facilitation activities in implementing a national safe patient handling program from the perspective of facility coordinators who implemented the program. METHODS: Using a qualitative descriptive design, data were collected in five focus groups at two international Safe Patient Handling and Mobility Conferences. Participants were 38 facility coordinators implementing a safe patient handling program in the Department of Veterans Affairs medical centers throughout the United States. Data were analyzed using direct content analysis to gather descriptions of internal facilitation. RESULTS: The internal facilitation process involved engaging multiple disciplines and levels of leadership for implementation. Fifty-four facilitation activities were identified, including five activities not currently listed in an existing taxonomy. Key characteristics and skills of facilitators included persistence, credibility and clinical experience, and leadership and project management experience. Themes were mapped onto an existing framework and taxonomy of facilitation activities. LINKING EVIDENCE TO ACTION: Internal facilitation is both an implementation intervention and a process involving a wide range of activities. The findings provide an understanding of what internal facilitators are doing to support practice changes and the characteristics and skills of internal facilitators that are likely to result in long-term organizational change. Five recommendations for action address organizations, senior leaders, and internal facilitators.

Using Clinical Narratives in Program and Curriculum Evaluation.

Background: Using personal experience stories as teaching tools, clinical narratives are an effective means for sharing the art of nursing practice and provide insight into nurses' critical thinking and clinical proficiency. Using clinical narratives to assess curriculum effectiveness provides important insights into changed practice and learning beyond the classroom. Aim: This article provides an example of using clinical narratives in the evaluation of the Department of Veterans Health Affairs Office of Nursing Services (ONS) Evidence Based Practice Curriculum (EBPC). Methods: As part of a larger mixed-method evaluation of the EBPC, clinical narrative methods were employed to describe one incident where participants (n=3) applied at least two of three evidence based practice components (best available evidence; clinical expertise; patient preference). Results: Examination of clinical narratives demonstrated successful application of key components of evidence based practice and an integration into individual nursing practice beyond data obtained from other evaluation methods. Conclusions: Incorporating rich clinical narratives into a rigorous mixed-method program evaluation protocol provides insights beyond information uptake, satisfaction, efficacy, or competency assessment scores.

Evaluating an Evidence-Based Practice Curriculum for Nurses Entering Clinical Practice in the Veterans Health Administration.

Introduction: The Veterans Health Administration (VHA) registered nurse (RN) Transition to Practice (TTP) program is a 1-year comprehensive, standardized curriculum taught for entry-level nurses to assist them in transitioning to VA-trained, competent, professional RNs. The TTP program includes revised modules on Evidence-Based Practice (EBP) clinical decision making. The revised curriculum emphasizes EBP as a problem-solving approach to clinical decision making rather than a project-based approach to implement practice changes. The goal of this quality improvement project was to evaluate the content, delivery, and outcomes of a revised Evidence-Based Practice Curriculum (EBPC) for use in the VHA RN TTP program. Methods: Focus groups were conducted with TTP coordinators, who teach the program and facility EBP content experts from 32 VHA Medical Centers. All attended a three-day face-to-face training at a central location. Qualitative data were managed and analyzed with a rapid assessment process. Discussion: Leaders within and outside of organizations are commonly believed to affect the success of implementing and sustaining any program or initiative through their influence on organizational climate, leadership processes, and leadership alignment across multiple levels of leadership. Our findings were in line with other research showing that leaders should prioritize EBP and fuel it with resources to create sustainable change. Conclusions: In conclusion, the EBPC was reviewed very favorably by all who planned to use it in their facilities in teaching the content to practicing registered nurses. Future evaluation will focus on the degree to which faculty use the program, how they use the modules, and what feedback nurses provide after exposure to EBPC.

Promotion of NEDD-CUL1 conjugate cleavage by COP9 signalosome.

SCF ubiquitin ligases control various processes by marking regulatory proteins for ubiquitin-dependent proteolysis. To illuminate how SCF complexes are regulated, we sought proteins that interact with the human SCF component CUL1. The COP9 signalosome (CSN), a suppressor of plant photomorphogenesis, associated with multiple cullins and promoted cleavage of the ubiquitin-like protein NEDD8 from Schizosaccharomyces pombe CUL1 in vivo and in vitro. Multiple NEDD8-modified proteins uniquely accumulated in CSN-deficient S. pombe cells. We propose that the broad spectrum of activities previously attributed to CSN subunits--including repression of photomorphogenesis, activation of JUN, and activation of p27 nuclear export--underscores the importance of dynamic cycles of NEDD8 attachment and removal in biological regulation.

Organelle DB: an updated resource of eukaryotic protein localization and function.

Organelle DB (http://organelledb.lsi.umich.edu) is a web-accessible relational database presenting a supplemented catalog of organelle-localized proteins and major protein complexes. Since its release in 2004, Organelle DB has grown by 20% to encompass over 30,000 proteins from 138 eukaryotic organisms. Each protein in Organelle DB is presented with its subcellular localization, primary sequence and a detailed description of its function, as available. All records in Organelle DB have been annotated using controlled vocabulary from the Gene Ontology consortium. Protein localization data are inherently visual, and Organelle DB is a significant repository of biological images, housing 1500 micrographs of yeast cells carrying stained proteins. Furthermore, we report here the development of Organelle View, an extension of Organelle DB for the interactive visualization of organelles and subcellular structures in the budding yeast Saccharomyces cerevisiae. Organelle View offers a dimensional representation of a yeast cell; users can search Organelle View for proteins of interest, and the organelles housing these proteins will be highlighted in the cell image. Among other applications, Organelle View may serve as an educational aid engaging introductory biology students through a visually 'fun' interface. Organelle View can be accessed from the Organelle DB home page or directly at http://organelleview.lsi.umich.edu.

Biomechanical evaluation of injury severity associated with patient falls from bed.

This study investigated the severity of injuries associated with falling from bed and the effectiveness of injury-prevention strategies. Injury criteria were calculated for head- and feet-first falls from six bed heights onto a tiled surface and floor mat. These values indicated a 25% chance of experiencing a serious head injury as a result of falling feet-first from a bed height of 97.5 cm onto a tiled surface. Risk of injury increased to 40% when extrapolated for the height added by bedrails. Using a floor mat decreased this risk to less than 1% for bedrail height for feet-first falls. Calculated impact forces indicated a risk of skull fracture when hitting the tiled surface. Floor mats and height-adjustable beds positioned to the lowest height should be used to decrease the risk of injury associated with falling from bed.

Chloride transporting capability of Calu-3 epithelia following persistent knockdown of the cystic fibrosis transmembrane conductance regulator, CFTR.

BACKGROUND AND PURPOSE: Calu-3 cells are derived from serous cells of human lung submucosal glands, a prime target for therapy in cystic fibrosis (CF). Calu-3 cells can be cultured to form epithelia capable of transepithelial transport of chloride. A CF Calu-3 cell is not available. EXPERIMENTAL APPROACH: A retroviral vector was used to cause persistent down regulation of CFTR using siRNA methodology, in Calu-3 cells. A Calu-3 cell line with CFTR content less than 5% of the original line has been established. Epithelia grown using the modified cells have been used in comparative studies of transporting capability. KEY RESULTS: All aspects of cAMP activated chloride secretion were attenuated in the epithelia with reduced CFTR content. However transporting capability was reduced less than the CFTR content. From studies with the CFTR channel inhibitor, GlyH-101, it was concluded that wild type Calu-3 cells have a reserve of CFTR channels not located in the membrane, but available for replacement, while in the modified Calu-3 cell line there was little or no reserve. Lubiprostone, a putative ClC-2 activator, increased transepithelial chloride secretion in both modified and wild type Calu-3 epithelia. Modified Calu-3 epithelia with the residual CFTR currents blocked with GlyH-101 responded equally well to lubiprostone as those without the blocking agent. CONCLUSIONS AND IMPLICATIONS: It appears that lubiprostone is capable of stimulating a non-CFTR dependent transepithelial chloride secretion in Calu-3 monolayers, with obvious implications for CF therapy. Cell lines, however, do not always reflect the behaviour of the native tissue with integrity.

Beta-adrenergic regulation of beta-actin mRNA abundance in mouse parotid glands by a post-transcriptional mechanism.

In the first 24 h after a single injection of the beta-adrenergic agonist isoprenaline to mice, the level of beta-actin mRNA in the parotid glands increased significantly above that observed in untreated mice. The increase was transient, reaching 11 times the normal level 18 h after treatment and declining thereafter. Repeated daily doses of isoprenaline did not result in any further increase in beta-actin mRNA. Nuclear transcription experiments showed that there was no increase in the transcription rate of the beta-actin gene 8 h after an injection of isoprenaline, although beta-actin mRNA levels were increasing at this time. Immunoblotting revealed an increase in beta-actin protein in parotid gland samples after isoprenaline treatment, although the increase was not to the same extent as the mRNA, perhaps indicating that degradation of beta-actin had also increased. Using immunocytochemistry it was found that beta-actin was located mainly in the apical cortex of the normal acinar cell. There was a significant decrease in cortical beta-actin 24 h after isoprenaline treatment, suggesting that the beta-actin was under the process of redistribution. From these data we propose that isoprenaline caused an increase in beta-actin synthesis by a posttranscriptional mechanism and a redistribution of beta-actin in preparation for the well-known subsequent change in morphology and function of the parotid glands.

Isoprenaline-induced and constitutive members of a proline-rich protein sub-group from mouse parotid glands studied with monoclonal antibody NAL1.

Members of the proline-rich protein (PRP) family of mouse parotid glands were analysed before and after stimulation with the beta-agonist isoprenaline by using a monoclonal antibody raised against the induced PRP A3(0) (GP-27). Antibody NAL1 reacted strongly with isoprenaline-induced B-type PRP precursors and their salivary counterparts, but not against the A-type PRPs A1(0) (Gp-66) and A2(0) (GP-45) or human salivary proteins, and it is likely that NAL1 recognizes a proline-rich repeat variant unique to this group of rodent PRPs. PRP-related antigens were observed in the parotid glands (N1(0) and N2(0] and saliva of normal mice. The antigens were located immunocytochemically in secretory granules of parotid acinar cells of both normal and isoprenaline-stimulated mice. The total amount of PRP antigens increased 16-fold from 2.5 to 40% of parotid protein after 10 days of isoprenaline treatment, as estimated by enzyme-linked immunosorbent assay. Immunoblotting showed that new PRP species appeared during the period of increase. After treatment with isoprenaline, B-type PRPs appeared first, followed by A3(0) and another member of the family. These results show that the mouse PRP family is larger than previously thought and can be divided immunologically into sub-groups. That a subset of PRPs are produced in the normal mouse indicates that there is differential beta-adrenergic regulation within the family, and also has implications for the role of PRPs in the normal maintenance of healthy dentition and other processes.

Randomized controlled trial of vasodilator therapy after myocardial infarction.

Hemodynamic changes and mortality and morbidity were compared in a randomized controlled trial of sodium nitroprusside after acute myocardial infarction. Fifty patients with a mean pulmonary capillary wedge pressure of more than 20 mm Hg within 24 hours of acute infarction were randomly assigned to one of two groups: 25 patients treated with nitroprusside and 25 treated with furosemide. Nitroprusside rapidly produced a sustained decrease in systemic vascular resistance and increase in cardiac index (thermodilution). After 1 hour the cardiac index had increased 16 +/- 3 (mean +/- standard error of the mean) percent (p less than 0.001) compared with a decrease of 7 +/- 3 percent with administration of furosemide (p less than 0.01). Differences in systemic vascular resistance and cardiac index in the two groups persisted throughout the 48 hour treatment period (p less than 0.001). Pulmonary capillary wedge pressure decreased rapidly with nitroprusside and slowly with furosemide so that, although it was significantly lower in the former group overall (p less than 0.001), by 48 hours the values were not different. Although beneficial acute hemodynamic effects of nitroprusside were demonstrated, there was no difference in mortality or in morbidity assessed clinically, by chest X-ray film, echocardiogram or graded treadmill stress testing after 6 months or 1 year.

Effects of low-dose aspirin on restenosis after coronary angioplasty.

After angioplasty of a previously untreated native coronary artery and after 2 weeks of aspirin therapy, 216 subjects (aged less than 70 years without acute infarction) were randomized to treatment with soluble aspirin, 100 mg/day, or placebo to study the effect on restenosis. Follow-up, defined as angiography at 6 months, earlier angiographic restenosis or coronary bypass surgery was completed by 108 aspirin- and 104 placebo-treated patients. Restenosis (stenosis greater than or equal to 50% plus loss of greater than or equal to 50% of gain, or surgery) occurred in 38 (35%) aspirin- and 45 (43%) placebo-treated subjects (p = not significant). No patient died. Restenosis occurred in 42 of 168 (25%) aspirin- and 51 of 135 (38%) placebo-treated lesions (p less than 0.025). Aspirin-treated lesions (n = 163) had lost 16 +/- 22% (mean +/- standard deviation) of lumen and placebo-treated lesions 22 +/- 25% of lumen (n = 134) at angiography (p less than 0.01). There were more left anterior descending lesions in the placebo group and these had a higher recurrence rate than other lesions. The beneficial effect of aspirin was not dependent on this, although significance was reduced in subgroup analysis. Loss of lumen in left anterior descending lesions was 20 +/- 24% (n = 57) in the aspirin-treated and 27 +/- 25% (n = 70) in the placebo-treated lesions (p less than 0.1). It is concluded that there is a small beneficial effect of low-dose aspirin on restenosis after coronary angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of glucose on insulin biosynthesis and beta cell ultrastructure in cultured fetal rat pancreas.

Pancreatic rudiments from 14-day fetal rats were cultured whole for 8 days in medium containing 5.5 or 16.5 mmol glucose/l (1G or 3G medium). Rudiments grown in 3G medium (3G cells) contained more DNA and insulin than those grown in 1G medium (1G cells) but there was no alteration in the insulin/DNA ratio or the fractional area of the rudiment occupied by insulin-containing cells. Morphometric analysis of ultrastructure revealed that the beta cells grown in 3G medium were smaller and had smaller nuclei than those grown in 1G medium. The size of exocrine cell nuclei in 1G or 3G medium was similar. Insulin granules occupied a greater proportion of the cytoplasmic volume in rudiments grown in 3G medium although the mean absolute volume of insulin granules per cell grown in 1G and 3G media was similar. Hence the residual cytoplasmic volume (cell--nucleus and granules) of 3G cells was less than that of 1G cells. Insulin granules from 3G cells had smaller granule sacs and cores than those from 1G cells. It is concluded that glucose stimulates the growth of rat fetal pancreas in vitro and has important effects on beta cell ultrastructure.

The fission yeast COP9/signalosome is involved in cullin modification by ubiquitin-related Ned8p.

BACKGROUND: The function of the fission yeast cullins Pcu1p and Pcu4p requires modification by the ubiquitin-related peptide Ned8p. A recent report by Lyapina et al. shows that the COP9/signalosome (CSN), a multifunctional eight subunit complex, regulates Ned8p modification of Pcu1p. Disruption of caa1/csn1, which encodes subunit 1 of the putative S. pombe CSN, results in accumulation of Pcu1p exclusively in the modified form. However, it remained unclear whether this reflects global control of all cullins by the entire CSN complex. RESULTS: We demonstrate that multiple CSN subunits control Ned8p modification of Pcu3p, another fission yeast cullin, which, in complex with the RING domain protein Pip1p, forms a ubiquitin ligase that functions in cellular stress response. Pcu3p is modified by Ned8p on Lys 729 and accumulates exclusively in the neddylated form in cells lacking the CSN subunits 1, 3, 4, and 5. These CSN subunits co-elute with Pcu3p in gel filtration fractions corresponding to approximately 550 kDa and specifically bind both native and Ned8p-modified Pcu3p in vivo. While CSN does not influence the subcellular localization of Pcu3p, Pcu3p-associated in vitro ubiquitin ligase activity is stimulated in the absence of CSN. CONCLUSIONS: Taken together, our data suggest that CSN is a global regulator of Ned8p modification of multiple cullins and potentially other proteins involved in cellular regulation.

A simple near-patient test for nicotine and its metabolites in urine to assess smoking habit.

We describe a disposable, near-patient urine test to monitor cigarette smoking. A plastic device contains the sealed dried reagents to measure nicotine and its metabolites, by a colorimetric assay. The device can be used to give a qualitative assessment of tobacco consumption, simply by observing a colour change. Alternatively, the test can be quantified by measuring the light absorbance with a simple colorimeter, and a concentration of nicotinic metabolites obtained with reference to a cotinine standard. A correction factor for the concentration of the urine sample, based on light absorbance, allows the result to be expressed as a ratio to urine concentration. This method correlates with reported daily cigarette consumption (r = 0.69, p < 0.0001) and compares favourably with cotinine, as measured by gas chromatography (r = 0.89, p < 0.0001). The method provides a simple-to-use, inexpensive way to monitoring tobacco consumption in extralaboratory situations.

Opioids and hibernation. I. Effects of naloxone on bear HIT'S depression of guinea pig ileum contractility and on induction of summer hibernation in the ground squirrel.

Summer hibernation in ground squirrels (Citellus tridecemlineatus) can be induced by intravenous injection of hibernation-induction trigger (HIT) from winter bear plasma or its albumin fraction. In this study, we show that bear HIT depresses electrically-induced contraction of the guinea pig ileum myenteric plexus-longitudinal muscle preparation, and that naloxone, at 100, 1,000, or even 4,000 nM, fails to reverse that effect. In a simultaneous study, four sets of ground squirrels were implanted with osmotic minipumps which delivered solutions at a controlled and continuous rate. Two of the groups had pumps delivering naloxone at 1 mg/kg body weight per hour. The other two groups had saline-filled pumps (controls). One set of squirrels from each of the saline- and naloxone-filled pump groups were then injected intravenously with winter bear plasma. The remaining two groups of squirrels were injected with winter bear albumin fraction. Hibernation frequency was determined by measurements of core temperature (from surgically-implanted radio capsules), respiratory rate, and bouts of activity. Squirrels with saline-filled pumps hibernated four times more frequently than the naloxone groups. To confirm these findings, three squirrels from each naloxone group were reinjected with bear HIT after removal of the pumps. These six squirrels then hibernated over four times their previous frequency. Results suggest that bear HIT is not itself an opioid (since naloxone did not reverse bear HIT's depression of electrically-induced contraction of guinea pig ileum). The fact that bear HIT's effect of inducing summer hibernation in ground squirrels is effectively blocked in vivo by naloxone leads to the speculation that HIT may be either a precursor of endogenous opioids or a potent releaser of them, which, in turn, induce hibernation.

Going public as an AIDS family caregiver.

Images of AIDS invoke fears of contagion, disability and formidable death, and moral overtones directed toward drug use, sexuality and sexual identity and freedom. Responses to these images are both private and public, and have profound consequences for individuals whose lives have been touched by the disease, both the person with AIDS and the family caregiver. The purpose of this paper is to analyze in detail 'going public,' one category of a substantive theory of AIDS family caregiving. This category was developed from a grounded theory study of 53 AIDS family members who were asked to describe their experiences as an AIDS family caregiver during an indepth interview. Data were content analyzed using constant comparative analysis. Going public referred to how AIDS family caregivers let others known that they were caring for a PWA. Specifically, going public entailed selecting appropriate persons and audiences to tell, formulating approaches to communicating information, and considering the risks and benefits of the possible choices. The description of going public as an AIDS family caregiver details the assertiveness involved in political action and social change, contrasted with the isolation and secrecy involved in maintaining relationships with others under the condition of a stigmatizing illness. Data revealed a particular emphasis on the phenomenon of 'guilt by association'. Because of their close relationship to a person with AIDS, caregivers were obligated to share the stigma of AIDS and were likewise discredited. Findings from our study emphasize the tremendous personal suffering experienced by caregivers which was associated with AIDS stigma in the form of rejection, loss of friends and harassment. Data also revealed the strong commitment of many caregivers to social activism which ranged from participating in educational efforts to marching in demonstrations. The rationale for the apparent increased activism among AIDS family caregivers compared to other groups of caregivers is explored. Going public highlights both the personal suffering and social manifestations of AIDS, significant issues to consider in planning health services for the second decade of the AIDS epidemic.

Near-patient test for nicotine and its metabolites in saliva to assess smoking habit.

Smoking is a major risk factor for periodontal disease, causing bone and tooth loss. Effective management of many oral conditions requires accurate information about smoking. We describe a disposable, 10-min, near-patient saliva test to monitor cigarette smoking. A plastic device contains the dried reagents to measure nicotine and its metabolites by a colorimetric assay. The device can be used to give a semi-quantitative assessment of tobacco consumption by observing a colour change and comparing it to a reference chart. Alternatively, the test can be quantified by measuring the light absorbance with a colorimeter and determining the concentration of nicotine metabolites by reference to a cotinine standard. This method correlates with reported daily cigarette consumption (r=0.62, P<0.0001) and nicotine yield of cigarettes smoked (r=0.35, P<0.01) and compares favourably with cotinine, as measured independently by radioimmunoassay (r=0.57, P<0.005). The method provides a simple-to-use, inexpensive way of monitoring tobacco consumption in dental surgeries.

Serum and tissue antioxidant capacity in cervical intraepithelial neoplasia investigated using an enhanced chemiluminescent reaction.

Depleted antioxidant defence has been implicated in the pathogenesis of cervical neoplasia. We determined the systemic and local antioxidant status of women with this condition. Thirty-four women with varying grades of cervical intraepithelial neoplasia, 25 patients who had been treated successfully with diathermy loop excision, and 56 women who had no evidence of cervical abnormality acted as controls. Total antioxidant capacity of serum and protein-free serum, and of neat and protein-free homogenized cervical punch biopsies were determined using enhanced chemiluminescence. Mean serum antioxidant capacity of patients with current neoplasia and treated patients was not significantly different from that of controls. However, mean antioxidant capacity of homogenized cervical tissue from women with neoplasia was significantly lower than control means (P < 0.005), while results for treated patients were intermediate between those from diseased and normal samples (P < 0.05). The enhanced chemiluminescence technique has potential as a suitable method for measuring total antioxidant capacity of cervical tissue, and warrants further investigations using other tissue types. Significant antioxidant depletion in cervical intra-epithelial neoplasia appears to be confined to the local cervical mucosa.