The optimal duration of infusion set use to prevent life-threatening catheter-related bloodstream infection (CRBSI) is unclear. We aimed to compare the effectiveness and costs of 7-day (intervention) ...versus 4-day (control) infusion set replacement to prevent CRBSI in patients with central venous access devices (tunnelled cuffed, non-tunnelled, peripherally inserted, and totally implanted) and peripheral arterial catheters.
We did a randomised, controlled, assessor-masked trial at ten Australian hospitals. Our hypothesis was CRBSI equivalence for central venous access devices and non-inferiority for peripheral arterial catheters (both 2% margin). Adults and children with expected greater than 24 h central venous access device–peripheral arterial catheter use were randomly assigned (1:1; stratified by hospital, catheter type, and intensive care unit or ward) by a centralised, web-based service (concealed before allocation) to infusion set replacement every 7 days, or 4 days. This included crystalloids, non-lipid parenteral nutrition, and medication infusions. Patients and clinicians were not masked, but the primary outcome (CRBSI) was adjudicated by masked infectious diseases physicians. The analysis was modified intention to treat (mITT). This study is registered with the Australian New Zealand Clinical Trials Registry ACTRN12610000505000 and is complete.
Between May 30, 2011, and Dec, 9, 2016, from 6007 patients assessed, we assigned 2944 patients to 7-day (n=1463) or 4-day (n=1481) infusion set replacement, with 2941 in the mITT analysis. For central venous access devices, 20 (1·78%) of 1124 patients (7-day group) and 16 (1·46%) of 1097 patients (4-day group) had CRBSI (absolute risk difference ARD 0·32%, 95% CI −0·73 to 1·37). For peripheral arterial catheters, one (0·28%) of 357 patients in the 7-day group and none of 363 patients in the 4-day group had CRBSI (ARD 0·28%, −0·27% to 0·83%). There were no treatment-related adverse events.
Infusion set use can be safely extended to 7 days with resultant cost and workload reductions.
Australian National Health and Medical Research Council.
ObjectivesRates of unused (‘idle’) peripheral intravenous catheters (PIVCs) are high but can vary per setting. Understanding factors that influence the decision-making of doctors, nurses and ...paramedics in the emergency setting regarding PIVC insertion, and what factors may modify their decision is essential to identify opportunities to reduce unnecessary cannulations and improve patient-centred outcomes. This study aimed to understand factors associated with clinicians’ decision-making on whether to insert or use a PIVC in the emergency care setting.DesignA qualitative descriptive study using in-depth semistructured interviews and thematic analysis.SettingGold Coast, Queensland, Australia, in a large tertiary level emergency department (ED) and local government ambulance service.ParticipantsParticipants recruited were ED clinicians (doctors, nurses) and paramedics who regularly insert PIVCs.ResultsFrom the 15 clinicians interviewed 4 key themes: knowledge and experience, complicated and multifactorial, convenience, anticipated patient clinical course, and several subthemes emerged relating to clinician decision-making across all disciplines. The first two themes focused on decision-making to gather data and evidence, such as knowledge and experience, and decisions being complicated and multifactorial. The remaining two themes related to the actions clinicians took such as convenience and anticipated patient clinical course.ConclusionThe decision to insert a PIVC is more complicated than clinicians, administrators and policy-makers may realise. When explored, clinician decisions were multifaceted with many factors influencing the decision to insert a PIVC. In actual practice, clinicians routinely insert PIVCs in most patients as a learnt reflex with little cognitive input. When considering PIVC insertion, more time needs to be devoted to the awareness of: (1) decision-making in the context of the clinician’s own experience, (2) cognitive biases and (3) patient-centred factors. Such awareness will support an appropriate risk assessment which will benefit the patient, clinician and healthcare system.
Stress is ubiquitous to life and can irreparably damage essential biomolecules and organelles in cells. To survive, organisms must sense and adapt to stressful conditions. One highly conserved ...adaptive stress response is through the posttranslational modification of proteins by the small ubiquitin-like modifier (SUMO). Here, we examine the effects of acute ethanol stress on protein sumoylation in the budding yeast
. We found that cells exhibit a transient sumoylation response after acute exposure to ≤7.5% vol/vol ethanol. By contrast, the sumoylation response becomes chronic at 10% ethanol exposure. Mass spectrometry analyses identified 18 proteins that are sumoylated after acute ethanol exposure, with 15 known to associate with chromatin. Upon further analysis, we found that the chromatin structural proteins Smc5 and Smc6 undergo ethanol-induced sumoylation that depends on the activity of the E3 SUMO ligase Mms21. Using cell-cycle arrest assays, we observed that Smc5 and Smc6 ethanol-induced sumoylation occurs during G1 and G2/M phases but not S phase. Acute ethanol exposure also resulted in the formation of Rad52 foci at levels comparable to Rad52 foci formation after exposure to the DNA alkylating agent methyl methanesulfonate (MMS). MMS exposure is known to induce the intra-S-phase DNA damage checkpoint via Rad53 phosphorylation, but ethanol exposure did not induce Rad53 phosphorylation. Ethanol abrogated the effect of MMS on Rad53 phosphorylation when added simultaneously. From these studies, we propose that acute ethanol exposure induces a change in chromatin leading to sumoylation of specific chromatin structural proteins.
•Conventional fluorescent proteins like GFP are restricted to aerobic environments.•Bilin-binding fluorescent proteins (BBFPs) enable live-cell imaging of anaerobes.•We implemented BBFPs to ...fluorescently label prevalent gut microbiome species.•The UnaG and IFP2.0 BBFPs can be used in multi-species multicolor microscopy.
Fluorescent tools such as green fluorescent protein (GFP) have been used extensively as reporters in biochemistry and microbiology, but GFP and other conventional fluorescent proteins are restricted to aerobic environments. This limitation precludes fluorescence studies of anaerobic ecologies including polymicrobial communities in the human gut microbiome and in soil microbiomes, which profoundly affect health, disease, and the environment. To address this limitation, we describe the first implementation of two bilin-binding fluorescent proteins (BBFPs), UnaG and IFP2.0, as oxygen-independent fluorescent labels for live-cell imaging in anaerobic bacteria. Expression of UnaG or IFP2.0 in the prevalent gut bacterium Bacteroides thetaiotaomicron (B. theta) results in detectable fluorescence upon the addition of the bilirubin or biliverdin ligand, even in anaerobic conditions. Furthermore, these BBFPs can be used in two-color imaging to differentiate cells expressing either UnaG or IFP2.0; UnaG and IFP2.0 can also be used to distinguish B. theta from other common gut bacterial species in mixed-culture live-cell imaging. BBFPs are promising fluorescent tools for live-cell imaging investigations of otherwise inaccessible anaerobic polymicrobial communities.
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TDP-43 aggregates are a salient feature of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and a variety of other neurodegenerative diseases, including Alzheimer’s disease (AD). ...With an anticipated growth in the most susceptible demographic, projections predict neurodegenerative diseases will potentially affect 15 million people in the United States by 2050. Currently, there are no cures for ALS, FTD, or AD. Previous studies of the amyloidogenic core of TDP-43 have demonstrated that oligomers greater than a trimer are associated with toxicity. Utilizing a joint pharmacophore space (JPS) method, potential drugs have been designed specifically for amyloid-related diseases. These molecules were generated on the basis of key chemical features necessary for blood–brain barrier permeability, low adverse side effects, and target selectivity. Combining ion-mobility mass spectrometry and atomic force microscopy with the JPS computational method allows us to more efficiently evaluate a potential drug’s efficacy in disrupting the development of putative toxic species. Our results demonstrate the dissociation of higher-order oligomers in the presence of these novel JPS-generated inhibitors into smaller oligomer species. Additionally, drugs approved by the Food and Drug Administration for the treatment of ALS were also evaluated and demonstrated to maintain higher-order oligomeric assemblies. Possible mechanisms for the observed action of the JPS molecules are discussed.
Bilin-binding fluorescent proteins like UnaG–bilirubin are noncovalent ligand-dependent reporters for oxygen-free microscopy but are restricted to blue and far-red fluorescence. Here we describe a ...high-throughput screening approach to provide a new UnaG–ligand pair that can be excited in the 532 nm green excitation microscopy channel. We identified a novel orange UnaG–ligand pair that maximally emits at 581 nm. Whereas the benzothiazole-based ligand itself is nominally fluorescent, the compound binds UnaG with high affinity (K d = 3 nM) to induce a 2.5-fold fluorescence intensity enhancement and a 10 nm red shift. We demonstrated this pair in the anaerobic fluorescence microscopy of the prevalent gut bacterium Bacteroides thetaiotaomicron and in Escherichia coli. This UnaG–ligand pair can also be coupled to IFP2.0-biliverdin to differentiate cells in mixed-species two-color imaging. Our results demonstrate the versatility of the UnaG ligand-binding pocket and extend the ability to image cells at longer wavelengths in anoxic environments.
Surface adsorption of a homologous series of pyridine carboxylic acids on a hydrated colloidal cerium dioxide (ceria) film is characterized using the combination of experimental and computationally ...determined infrared (IR) spectra. Experimental analyses employ attenuated total reflectance (ATR) IR spectroscopy of deposited colloidal ceria thin films equilibrated with three pyridine carboxylic acids at pH 3.0, 5.5, and 8.5. The corresponding computational IR spectra for the energy-minimized intermediate and base forms of the pyridine carboxylic acids use density functional theory calculations at the B3LYP/6-311++G** level of theory. Solvent effects are modeled using both the COSMO implicit solvation model and the inclusion of explicit water molecules. Experimental IR spectra show that the adsorptive interactions between the pyridine carboxylic acids and ceria surface are due to the outer-sphere coordination of cerium ions in the films. Vibrational assignments based on combined experimental and computational results indicate that both pyridyl ring nitrogen and carboxylate functional groups account for the interaction of pyridine carboxylic acids at ceria surfaces. Experimentally determined Langmuir constants point to the intermediate form of picolinic acid (pyridine-2-carboxylic acid) as having the strongest adsorption to ceria compared to the other pyridine carboxylic acids investigated. The enhanced adsorption of picolinic acid is attributed to the adjacency of the protonated pyridyl nitrogen and the carboxylate group relative to nicotinic acid (pyridine-3-carboxylic acid) and isonicotinic acid (pyridine-4-carboxylic acid).
Background
The tubing (administration set) attached to both venous and arterial catheters may contribute to bacteraemia and other infections. The rate of infection may be increased or decreased by ...routine replacement of administration sets. This review was originally published in 2005 and was updated in 2012.
Objectives
The objective of this review was to identify any relationship between the frequency with which administration sets are replaced and rates of microbial colonization, infection and death.
Search methods
We searched The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 6), MEDLINE (1950 to June 2012), CINAHL (1982 to June 2012), EMBASE (1980 to June 2012), reference lists of identified trials and bibliographies of published reviews. The original search was performed in February 2004. We also contacted researchers in the field. We applied no language restriction.
Selection criteria
We included all randomized or controlled clinical trials on the frequency of venous or arterial catheter administration set replacement in hospitalized participants.
Data collection and analysis
Two review authors assessed all potentially relevant studies. We resolved disagreements between the two review authors by discussion with a third review author. We collected data for seven outcomes: catheter‐related infection; infusate‐related infection; infusate microbial colonization; catheter microbial colonization; all‐cause bloodstream infection; mortality; and cost. We pooled results from studies that compared different frequencies of administration set replacement, for instance, we pooled studies that compared replacement ≥ every 96 hours versus every 72 hours with studies that compared replacement ≥ every 48 hours versus every 24 hours.
Main results
We identified 26 studies for this updated review, 10 of which we excluded; six did not fulfil the inclusion criteria and four did not report usable data. We extracted data from the remaining 18 references (16 studies) with 5001 participants: study designs included neonate and adult populations, arterial and venous administration sets, parenteral nutrition, lipid emulsions and crystalloid infusions. Most studies were at moderate to high risk of bias or did not adequately describe the methods that they used to minimize bias. All included trials were unable to blind personnel because of the nature of the intervention.
No evidence was found for differences in catheter‐related or infusate‐related bacteraemia or fungaemia with more frequent administration set replacement overall or at any time interval comparison (risk ratio (RR) 1.06, 95% confidence interval (CI) 0.67 to 1.69; RR 0.67, 95% CI 0.27 to 1.70). Infrequent administration set replacement reduced the rate of bloodstream infection (RR 0.73, 95% CI 0.54 to 0.98). No evidence revealed differences in catheter colonization or infusate colonization with more frequent administration set replacement (RR 1.08, 95% CI 0.94 to 1.24; RR 1.15, 95% CI 0.70 to 1.86, respectively). Borderline evidence suggested that infrequent administration set replacement increased the mortality rate only within the neonatal population (RR 1.84, 95% CI 1.00 to 3.36). No evidence revealed interactions between the (lack of) effects of frequency of administration set replacement and the subgroups analysed: parenteral nutrition and/or fat emulsions versus infusates not involving parenteral nutrition or fat emulsions; adult versus neonatal participants; and arterial versus venous catheters.
Authors' conclusions
Some evidence indicates that administration sets that do not contain lipids, blood or blood products may be left in place for intervals of up to 96 hours without increasing the risk of infection. Other evidence suggests that mortality increased within the neonatal population with infrequent administration set replacement. However, much the evidence obtained was derived from studies of low to moderate quality.
Leaf-cutter ants are one of the most important herbivorous insects in the Neotropics, harvesting vast quantities of fresh leaf material. The ants use leaves to cultivate a fungus that serves as the ...colony's primary food source. This obligate ant-fungus mutualism is one of the few occurrences of farming by non-humans and likely facilitated the formation of their massive colonies. Mature leaf-cutter ant colonies contain millions of workers ranging in size from small garden tenders to large soldiers, resulting in one of the most complex polymorphic caste systems within ants. To begin uncovering the genomic underpinnings of this system, we sequenced the genome of Atta cephalotes using 454 pyrosequencing. One prediction from this ant's lifestyle is that it has undergone genetic modifications that reflect its obligate dependence on the fungus for nutrients. Analysis of this genome sequence is consistent with this hypothesis, as we find evidence for reductions in genes related to nutrient acquisition. These include extensive reductions in serine proteases (which are likely unnecessary because proteolysis is not a primary mechanism used to process nutrients obtained from the fungus), a loss of genes involved in arginine biosynthesis (suggesting that this amino acid is obtained from the fungus), and the absence of a hexamerin (which sequesters amino acids during larval development in other insects). Following recent reports of genome sequences from other insects that engage in symbioses with beneficial microbes, the A. cephalotes genome provides new insights into the symbiotic lifestyle of this ant and advances our understanding of host-microbe symbioses.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IntroductionPeripheral intravenous catheters (PIVCs) are the most commonly used vascular access device in hospitalised patients. Yet PIVCs may be complicated by local or systemic infections leading ...to increased healthcare costs. Chlorhexidine gluconate (CHG)-impregnated dressings may help reduce PIVC-related infectious complications but have not yet been evaluated. We hypothesise an impregnated CHG transparent dressing, in comparison to standard polyurethane dressing, will be safe, effective and cost-effective in protecting against PIVC-related infectious complications and phlebitis.Methods and analysisThe ProP trial is a multicentre, superiority, randomised clinical and cost-effectiveness trial with internal pilot, conducted across three centres in Australia and France. Patients (adults and children aged ≥6 years) requiring one PIVC for ≥48 hours are eligible. We will exclude patients with emergent PIVCs, known CHG allergy, skin injury at site of insertion or previous trial enrolment. Patients will be randomised to 3M Tegaderm Antimicrobial IV Advanced Securement dressing or standard care group. For the internal pilot, 300 patients will be enrolled to test protocol feasibility (eligibility, recruitment, retention, protocol fidelity, missing data and satisfaction of participants and staff), primary endpoint for internal pilot, assessed by independent data safety monitoring committee. Clinical outcomes will not be reviewed. Following feasibility assessment, the remaining 2624 (1312 per trial arm) patients will be enrolled following the same methods. The primary endpoint is a composite of catheter-related infectious complications and phlebitis. Recruitment began on 3 May 2023.Ethics and disseminationThe protocol was approved by Ouest I ethic committee in France and by The Queensland Children’s Hospital Human Research Ethics Committee in Australia. The findings will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals.Trial registration numberNCT05741866.
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