Implementation of the "FASTHUG" concept decreases the incidence of ventilator-associated pneumonia in a surgical intensive care unit

<p>Abstract</p> <p>Background</p> <p>Ventilator-associated pneumonia (VAP) is a leading cause of morbidity and mortality in critically ill patients. The Institute for Healthcare Improvement 100,000 Lives Campaign made VAP a target of prevention and performance improvement. Additionally, the Joint Commission on Accreditation of Health Organizations' 2007 Disease Specific National Patient Safety Goals included the reduction of healthcare-associated infections. We report implementation of a performance improvement project that dramatically reduced our VAP rate that had exceeded the 90^thpercentile nationally.</p> <p>Methods</p> <p>From 1 January 2004 to 31 December 2005 a performance improvement project was undertaken to decrease our critical care unit VAP rate. In year one (2004) procedural interventions were highlighted: aggressive oral care, early extubation, management of soiled or malfunctioning respiratory equipment, hand washing surveillance, and maximal sterile barrier precautions. In year two (2005) an evaluative concept called FASTHUG (daily evaluation of patients' feeding, analgesia, sedation, thromboembolic prophylaxis, elevation of the head of the bed, ulcer prophylaxis, and glucose control) was implemented. To determine the long-term effectiveness of such an intervention a historical control period (2003) and the procedural intervention period of 2004, i.e., the pre-FASTHUG period (months 1–24) were compared with an extended post-FASTHUG period (months 25–54).</p> <p>Results</p> <p>The 2003 surgical intensive care VAP rate of 19.3/1000 ventilator-days served as a historical control. Procedural interventions in 2004 were not effective in reducing VAP, p = 0.62. However, implementation of FASTHUG in 2005, directed by a critical care team, resulted in a rate of 7.3/1000 ventilator-days, p ≤ .01. The median pneumonia rate was lower after implementation of FASTHUG when compared to the historical control year (p = .028) and the first year after the procedural interventions (p = .041) using follow-up pairwise comparisons. The pre-FASTHUG period (2003–2004, months 1–24) when compared with an extended post-FASTHUG period (2005–2007, 25–54 months) also demonstrated a significant decrease in the VAP rate, p = .0004. This reduction in the post-FASTHUG period occurred despite a rising Severity of Illness index in critically ill patients, p = .001.</p> <p>Conclusion</p> <p>Implementation of the FASTHUG concept, in the daily evaluation of mechanically ventilated patients, significantly decreased our surgical intensive care unit VAP rate.</p

Female germ unit in Genlisea and Utricularia, with remarks about the evolution of the extra-ovular female gametophyte in members of Lentibulariaceae

Lentibulariaceae is the largest family among carnivorous plants which displays not only an unusual morphology and anatomy but also the special evolution of its embryological characteristics. It has previously been reported by authors that Utricularia species lack a filiform apparatus in the synergids. The main purposes of this study were to determine whether a filiform apparatus occurs in the synergids of Utricularia and its sister genus Genlisea, and to compare the female germ unit in these genera. The present studies clearly show that synergids in both genera possess a filiform apparatus; however, it seems that Utricularia quelchii synergids have a simpler structure compared to Genlisea aurea and other typical angiosperms. The synergids are located at the terminal position in the embryo sacs of Pinguicula, Genlisea and were probably also located in that position in common Utricularia ancestor. This ancestral characteristic still occurs in some species from the Bivalvaria subgenus. An embryo sac, which grows out beyond the limit of the integument and has contact with nutritive tissue, appeared independently in different Utricularia lineages and as a consequence of this, the egg apparatus changes position from apical to lateral

Pride and confidence at work: potential predictors of occupational health in a hospital setting

BACKGROUND: This study focuses on determinants of a healthy work environment in two departments in a Swedish university hospital. The study is based on previously conducted longitudinal studies at the hospital (1994–2001), concerning working conditions and health outcomes among health care personnel in conjunction with downsizing processes. Overall, there was a general negative trend in relation to mental health, as well as long-term sick leave during the study period. The two departments chosen for the current study differed from the general hospital trend in that they showed stable health development. The aim of the study was to identify and analyse experiential determinants of healthy working conditions. METHODS: Thematic open-ended interviews were carried out with seventeen managers and key informants, representing different groups of co-workers in the two departments. The interviews were transcribed verbatim and an inductive content analysis was made. RESULTS: In the two studied departments the respondents perceived that it was advantageous to belong to a small department, and to work in cooperation-oriented care. The management approaches described by both managers and co-workers could be interpreted as transformational, due to a strain of visionary, delegating, motivating, confirmative, supportive attitudes and a strongly expressed solution-oriented attitude. The daily work included integrated learning activities. The existing organisational conditions, approaches and attitudes promoted tendencies towards a work climate characterised by trust, team spirit and professionalism. In the description of the themes organisational conditions, approaches and climate, two core determinants, work-pride and confidence, for healthy working conditions were interpreted. Our core determinants augment the well-established concepts: manageability, comprehensiveness and meaningfulness. These favourable conditions seem to function as a buffer against the general negative effects of downsizing observed elsewhere in the hospital, and in the literature. CONCLUSION: Research illuminating health-promoting aspects is rather unusual. This study could be seen as explorative. The themes and core dimensions we found could be used as a basis for further intervention studies in similar health-care settings. The result could also be used in future health promotion studies in larger populations. One of the first steps in such a strategy is to formulate relevant questions, and we consider that this study contributes to this

Efficient Visual Search from Synchronized Auditory Signals Requires Transient Audiovisual Events

BACKGROUND: A prevailing view is that audiovisual integration requires temporally coincident signals. However, a recent study failed to find any evidence for audiovisual integration in visual search even when using synchronized audiovisual events. An important question is what information is critical to observe audiovisual integration. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that temporal coincidence (i.e., synchrony) of auditory and visual components can trigger audiovisual interaction in cluttered displays and consequently produce very fast and efficient target identification. In visual search experiments, subjects found a modulating visual target vastly more efficiently when it was paired with a synchronous auditory signal. By manipulating the kind of temporal modulation (sine wave vs. square wave vs. difference wave; harmonic sine-wave synthesis; gradient of onset/offset ramps) we show that abrupt visual events are required for this search efficiency to occur, and that sinusoidal audiovisual modulations do not support efficient search. CONCLUSIONS/SIGNIFICANCE: Thus, audiovisual temporal alignment will only lead to benefits in visual search if the changes in the component signals are both synchronized and transient. We propose that transient signals are necessary in synchrony-driven binding to avoid spurious interactions with unrelated signals when these occur close together in time

Bone Marrow Stromal Cells Modulate Mouse ENT1 Activity and Protect Leukemia Cells from Cytarabine Induced Apoptosis

BACKGROUND: Despite a high response rate to chemotherapy, the majority of patients with acute myeloid leukemia (AML) are destined to relapse due to residual disease in the bone marrow (BM). The tumor microenvironment is increasingly being recognized as a critical factor in mediating cancer cell survival and drug resistance. In this study, we propose to identify mechanisms involved in the chemoprotection conferred by the BM stroma to leukemia cells. METHODS: Using a leukemia mouse model and a human leukemia cell line, we studied the interaction of leukemia cells with the BM microenvironment. We evaluated in vivo and in vitro leukemia cell chemoprotection to different cytotoxic agents mediated by the BM stroma. Leukemia cell apoptosis was assessed by flow cytometry and western blotting. The activity of the equilibrative nucleoside transporter 1 (ENT1), responsible for cytarabine cell incorporation, was investigated by measuring transport and intracellular accumulation of (3)H-adenosine. RESULTS: Leukemia cell mobilization from the bone marrow into peripheral blood in vivo using a CXCR4 inhibitor induced chemo-sensitization of leukemia cells to cytarabine, which translated into a prolonged survival advantage in our mouse leukemia model. In vitro, the BM stromal cells secreted a soluble factor that mediated significant chemoprotection to leukemia cells from cytarabine induced apoptosis. Furthermore, the BM stromal cell supernatant induced a 50% reduction of the ENT1 activity in leukemia cells, reducing the incorporation of cytarabine. No protection was observed when radiation or other cytotoxic agents such as etoposide, cisplatin and 5-fluorouracil were used. CONCLUSION: The BM stroma secretes a soluble factor that significantly protects leukemia cells from cytarabine-induced apoptosis and blocks ENT1 activity. Strategies that modify the chemo-protective effects mediated by the BM microenvironment may enhance the benefit of conventional chemotherapy for patients with AML

A Portrait of the Transcriptome of the Neglected Trematode, Fasciola gigantica—Biological and Biotechnological Implications

Fasciola gigantica (Digenea) is an important foodborne trematode that causes liver fluke disease (fascioliasis) in mammals, including ungulates and humans, mainly in tropical climatic zones of the world. Despite its socioeconomic impact, almost nothing is known about the molecular biology of this parasite, its interplay with its hosts, and the pathogenesis of fascioliasis. Modern genomic technologies now provide unique opportunities to rapidly tackle these exciting areas. The present study reports the first transcriptome representing the adult stage of F. gigantica (of bovid origin), defined using a massively parallel sequencing-coupled bioinformatic approach. From >20 million raw sequence reads, >30,000 contiguous sequences were assembled, of which most were novel. Relative levels of transcription were determined for individual molecules, which were also characterized (at the inferred amino acid level) based on homology, gene ontology, and/or pathway mapping. Comparisons of the transcriptome of F. gigantica with those of other trematodes, including F. hepatica, revealed similarities in transcription for molecules inferred to have key roles in parasite-host interactions. Overall, the present dataset should provide a solid foundation for future fundamental genomic, proteomic, and metabolomic explorations of F. gigantica, as well as a basis for applied outcomes such as the development of novel methods of intervention against this neglected parasite

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC