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1.
Cell ; 144(5): 745-56, 2011 Mar 04.
Article in English | MEDLINE | ID: mdl-21376235

ABSTRACT

The Mpk1 MAPK of the yeast cell wall integrity pathway uses a noncatalytic mechanism to activate transcription of stress-induced genes by recruitment of initiation factors to target promoters. We show here that Mpk1 additionally serves a function in transcription elongation that is also independent of its catalytic activity. This function is mediated by an interaction between Mpk1 and the Paf1 subunit of the Paf1C elongation complex. A mutation in Paf1 that blocks this interaction causes a specific defect in transcription elongation of an Mpk1-induced gene, which results from Sen1-dependent premature termination through a Nab3-binding site within the promoter-proximal region of the gene. Our findings reveal a regulatory mechanism in which Mpk1 overcomes transcriptional attenuation by blocking recruitment of the Sen1-Nrd1-Nab3 termination complex to the elongating polymerase. Finally, we demonstrate that this mechanism is conserved in an interaction between the human ERK5 MAPK and human Paf1.


Subject(s)
DNA Helicases/metabolism , Nuclear Proteins/metabolism , RNA Helicases/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/metabolism , Transcription, Genetic , Glucosyltransferases/metabolism , Humans , Membrane Proteins/metabolism , Mitogen-Activated Protein Kinase 7/metabolism , Mitogen-Activated Protein Kinases/metabolism , Promoter Regions, Genetic , Transcription Factors
2.
Appl Environ Microbiol ; : e0069924, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38869300

ABSTRACT

Genome editing in non-model bacteria is important to understand gene-to-function links that may differ from those of model microorganisms. Although species of the Burkholderia cepacia complex (Bcc) have great biotechnological capacities, the limited genetic tools available to understand and mitigate their pathogenic potential hamper their utilization in industrial applications. To broaden the genetic tools available for Bcc species, we developed RhaCAST, a targeted DNA insertion platform based on a CRISPR-associated transposase driven by a rhamnose-inducible promoter. We demonstrated the utility of the system for targeted insertional mutagenesis in the Bcc strains B. cenocepacia K56-2 and Burkholderia multivorans ATCC17616. We showed that the RhaCAST system can be used for loss- and gain-of-function applications. Importantly, the selection marker could be excised and reused to allow iterative genetic manipulation. The RhaCAST system is faster, easier, and more adaptable than previous insertional mutagenesis tools available for Bcc species and may be used to disrupt pathogenicity elements and insert relevant genetic modules, enabling Bcc biotechnological applications. IMPORTANCE: Species of the Burkholderia cepacia complex (Bcc) have great biotechnological potential but are also opportunistic pathogens. Genetic manipulation of Bcc species is necessary to understand gene-to-function links. However, limited genetic tools are available to manipulate Bcc, hindering our understanding of their pathogenic traits and their potential in biotechnological applications. We developed a genetic tool based on CRISPR-associated transposase to increase the genetic tools available for Bcc species. The genetic tool we developed in this study can be used for loss and gain of function in Bcc species. The significance of our work is in expanding currently available tools to manipulate Bcc.

3.
Pediatr Radiol ; 2024 May 23.
Article in English | MEDLINE | ID: mdl-38777883

ABSTRACT

BACKGROUND: Moyamoya is a progressive, non-atherosclerotic cerebral arteriopathy that may present in childhood and currently has no cure. Early diagnosis is critical to prevent a lifelong risk of neurological morbidity. Blood-oxygen-level-dependent (BOLD) MRI cerebrovascular reactivity (CVR) imaging provides a non-invasive, in vivo measure of autoregulatory capacity and cerebrovascular reserve. However, non-compliant or younger children require general anesthesia to achieve BOLD-CVR imaging. OBJECTIVE: To determine the same-day repeatability of BOLD-CVR imaging under general anesthesia in children with moyamoya. MATERIALS AND METHODS: Twenty-eight examination pairs were included (mean patient age = 7.3 ± 4.0 years). Positive and negatively reacting voxels were averaged over signals and counted over brain tissue and vascular territory. The intraclass correlation coefficient (ICC), Wilcoxon signed-rank test, and Bland-Altman plots were used to assess the variability between the scans. RESULTS: There was excellent-to-good (≥ 0.59) within-day repeatability in 18 out of 28 paired studies (64.3%). Wilcoxon signed-rank tests demonstrated no significant difference in the grey and white matter CVR estimates, between repeat scans (all p-values > 0.05). Bland-Altman plots of differences in mean magnitude of positive and negative and fractional positive and negative CVR estimates illustrated a reasonable degree of agreement between repeat scans and no systematic bias. CONCLUSION: BOLD-CVR imaging provides repeatable assessment of cerebrovascular reserve in children with moyamoya imaged under general anesthesia.

4.
J Comput Assist Tomogr ; 47(2): 229-235, 2023.
Article in English | MEDLINE | ID: mdl-36573321

ABSTRACT

OBJECTIVE: To evaluate the diagnostic quality of photon-counting detector (PCD) computed tomography (CT) in patients undergoing lung cancer screening compared with conventional energy-integrating detector (EID) CT in a prospective multireader study. MATERIALS: Patients undergoing lung cancer screening with conventional EID-CT were prospectively enrolled and scanned on a PCD-CT system using similar automatic exposure control settings and reconstruction kernels. Three thoracic radiologists blinded to CT system compared PCD-CT and EID-CT images and scored examinations using a 5-point Likert comparison score (-2 [left image is worse] to +2 [left image is better]) for artifacts, sharpness, image noise, diagnostic image quality, emphysema visualization, and lung nodule evaluation focusing on the border. Post hoc correction of Likert scores was performed such that they reflected PCD-CT performance in comparison to EID-CT. A nonreader radiologist measured objective image noise. RESULTS: Thirty-three patients (mean, 66.9 ± 5.6 years; 11 female; body mass index; 30.1 ± 5.1 kg/m 2 ) were enrolled. Mean volume CT dose index for PCD-CT was lower (0.61 ± 0.21 vs 0.73 ± 0.22; P < 0.001). Pooled reader results showed significant differences between imaging modalities for all comparative rankings ( P < 0.001), with PCD-CT favored for sharpness, image noise, image quality, and emphysema visualization and lung nodule border, but not artifacts. Photon-counting detector CT had significantly lower image noise (74.4 ± 10.5 HU vs 80.1 ± 8.6 HU; P = 0.048). CONCLUSIONS: Photon-counting detector CT with similar acquisition and reconstruction settings demonstrated improved image quality and less noise despite lower radiation dose, with improved ability to depict pulmonary emphysema and lung nodule borders compared with EID-CT at low-dose lung cancer CT screening.


Subject(s)
Emphysema , Lung Neoplasms , Pulmonary Emphysema , Humans , Female , Early Detection of Cancer , Prospective Studies , Lung Neoplasms/diagnostic imaging , Photons , Phantoms, Imaging , Tomography, X-Ray Computed/methods
5.
Paediatr Anaesth ; 33(11): 938-945, 2023 11.
Article in English | MEDLINE | ID: mdl-37555370

ABSTRACT

BACKGROUND: Liver transplantation is the life-saving treatment for many end-stage pediatric liver diseases. The perioperative course, including surgical and anesthetic factors, have an important influence on the trajectory of this high-risk population. Given the complexity and variability of the immediate postoperative course, there would be utility in identifying risk factors that allow prediction of adverse outcomes and intensive care unit trajectories. AIMS: The aim of this study was to develop and validate a risk prediction model of prolonged intensive care unit length of stay in the pediatric liver transplant population. METHODS: This is a retrospective analysis of consecutive pediatric isolated liver transplant recipients at a single institution between April 1, 2013 and April 30, 2020. All patients under the age of 18 years receiving a liver transplant were included in the study (n = 186). The primary outcome was intensive care unit length of stay greater than 7 days. RESULTS: Recipient and donor characteristics were used to develop a multivariable logistic regression model. A total of 186 patients were included in the study. Using multivariable logistic regression, we found that age < 12 months (odds ratio 4.02, 95% confidence interval 1.20-13.51, p = .024), metabolic or cholestatic disease (odds ratio 2.66, 95% confidence interval 1.01-7.07, p = .049), 30-day pretransplant hospital admission (odds ratio 8.59, 95% confidence interval 2.27-32.54, p = .002), intraoperative red blood cells transfusion >40 mL/kg (odds ratio 3.32, 95% confidence interval 1.12-9.81, p = .030), posttransplant return to the operating room (odds ratio 11.45, 95% confidence interval 3.04-43.16, p = .004), and major postoperative respiratory event (odds ratio 32.14, 95% confidence interval 3.00-343.90, p < .001) were associated with prolonged intensive care unit length of stay. The model demonstrates a good discriminative ability with an area under the receiver operative curve of 0.888 (95% confidence interval, 0.824-0.951). CONCLUSIONS: We develop and validate a model to predict prolonged intensive care unit length of stay in pediatric liver transplant patients using risk factors from all phases of the perioperative period.


Subject(s)
Liver Transplantation , Humans , Child , Adolescent , Infant , Retrospective Studies , Length of Stay , Intensive Care Units , Risk Factors
6.
Int J Mol Sci ; 24(5)2023 Feb 24.
Article in English | MEDLINE | ID: mdl-36901931

ABSTRACT

Although many bacterial lipases and PHA depolymerases have been identified, cloned, and characterized, there is very little information on the potential application of lipases and PHA depolymerases, especially intracellular enzymes, for the degradation of polyester polymers/plastics. We identified genes encoding an intracellular lipase (LIP3), an extracellular lipase (LIP4), and an intracellular PHA depolymerase (PhaZ) in the genome of the bacterium Pseudomonas chlororaphis PA23. We cloned these genes into Escherichia coli and then expressed, purified, and characterized the biochemistry and substrate preferences of the enzymes they encode. Our data suggest that the LIP3, LIP4, and PhaZ enzymes differ significantly in their biochemical and biophysical properties, structural-folding characteristics, and the absence or presence of a lid domain. Despite their different properties, the enzymes exhibited broad substrate specificity and were able to hydrolyze both short- and medium-chain length polyhydroxyalkanoates (PHAs), para-nitrophenyl (pNP) alkanoates, and polylactic acid (PLA). Gel Permeation Chromatography (GPC) analyses of the polymers treated with LIP3, LIP4, and PhaZ revealed significant degradation of both the biodegradable as well as the synthetic polymers poly(ε-caprolactone) (PCL) and polyethylene succinate (PES).


Subject(s)
Polyhydroxyalkanoates , Pseudomonas chlororaphis , Pseudomonas/metabolism , Carboxylic Ester Hydrolases/metabolism , Lipase/metabolism , Polyesters/metabolism , Polyhydroxyalkanoates/metabolism , Pseudomonas chlororaphis/genetics , Substrate Specificity
7.
J Environ Manage ; 340: 117859, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37121010

ABSTRACT

In this article, we identify the problem of plastic proliferation, the consequent expansion of plastic waste in our society, the inadequacies of current attempts to recycle plastic, and the urgency to address this problem in the light of the microplastic threat. It details the problems with current efforts to recycle plastic and the particularly poor recycling rates in North America (NA) when compared to certain countries in the European Union (EU). The obstacles to plastic recycling are overlapping economic, physical and regulatory problems spanning fluctuating resale market prices, residue and polymer contamination and offshore export which often circumvents the entire process. The primary differences between the EU and NA are the costs of end-of-life disposal methods with most EU citizens paying much higher prices for both landfilling and Energy from Waste (incineration) costs compared with NA. At the time of writing, some EU states are either restricted from landfilling mixed plastic waste or the cost is significantly greater than in NA ($80 to 125 USD/t vs $55 USD/t). This makes recycling a favourable option in the EU, and, in turn, has led to more industrial processing and innovation, more recycled product uptake, and the structuring of collection and sorting methods that favour cleaner polymer streams. This is a self-re-enforcing cycle and is evident by EU technologies and industries that have emerged to process "problem plastics", such as mixed plastic film wastes, co-polymer films, thermosets, Polystyrene, (PS) Polyvinyl Chloride (PVC), and others. This is in contrast with NA recycling infrastructure, which has been tailored to shipping low-value mixed plastic waste abroad. Circularity is far from complete in any jurisdiction as export of plastic to developing countries is an opaque, but often used disposal method in the EU as it is in NA. Proposed restrictions on off-shore shipping and regulations requiring minimum recycled plastic content in new products will potentially increase plastic recycling by increasing both supply and demand for recycled product.


Subject(s)
Plastics , Waste Management , Plastics/chemistry , Europe , Polymers , Polystyrenes , European Union , Recycling , Waste Management/methods
8.
J Environ Manage ; 317: 115416, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-35653839

ABSTRACT

Conventional oil spill recovery may cause significant damage to shoreline habitats during the removal of oiled material and from human and equipment interaction. In addition, these methods are costly and can leave a significant amount of residual oil in the environment. Biological remediation strategies may be a less invasive option for recovering oil from sensitive regions, with potential to increase recovery. Floating treatment wetlands are a growing area of interest for biodegradation of oil facilitated by plant-bacterial partnerships. Plants are able to stimulate microbial colonization in the rhizosphere, creating greater opportunity for contaminant interaction and degradation. A literature review analysis revealed thirteen articles researching this topic, and found that floating treatment wetlands have high potential to degrade oil contaminants. In some instances, plants and inoculated bacteria exhibited the highest degradation potential, however, plants alone had higher degradation potential than bacteria alone. Research is needed to explore how floating treatment wetlands perform in field-based trials and under variable environmental conditions.


Subject(s)
Petroleum Pollution , Petroleum , Bacteria/metabolism , Biodegradation, Environmental , Humans , Petroleum/metabolism , Petroleum Pollution/analysis , Rhizosphere , Wetlands
9.
Radiology ; 298(3): 486-491, 2021 03.
Article in English | MEDLINE | ID: mdl-33346696

ABSTRACT

Background The Value-Based Healthcare (VBH) concept is designed to improve individual healthcare outcomes without increasing expenditure, and is increasingly being used to determine resourcing of and reimbursement for medical services. Radiology is a major contributor to patient and societal healthcare at many levels. Despite this, some VBH models do not acknowledge radiology's central role; this may have future negative consequences for resource allocation. Methods, findings and interpretation This multi-society paper, representing the views of Radiology Societies in Europe, the USA, Canada, Australia, and New Zealand, describes the place of radiology in VBH models and the health-care value contributions of radiology. Potential steps to objectify and quantify the value contributed by radiology to healthcare are outlined. Published under a CC BY 4.0 license.


Subject(s)
Delivery of Health Care/standards , Radiology/standards , Value-Based Purchasing , Consensus , Cost Control , Delivery of Health Care/economics , Humans , Internationality , Radiology/economics , Societies, Medical
10.
FEMS Yeast Res ; 21(2)2021 03 18.
Article in English | MEDLINE | ID: mdl-33571365

ABSTRACT

Oleaginous yeasts have the ability to store greater than 20% of their mass as neutral lipids, in the form of triacylglycerides. The ATP citrate lyase is thought to play a key role in triacylglyceride synthesis, but the relationship between expression levels of this and other related enzymes is not well understood in the role of total lipid accumulation conferring the oleaginous phenotype. We conducted comparative proteomic analyses with the oleaginous yeast, Yarrowia lipolytica, grown in either nitrogen-sufficient rich media or nitrogen-limited minimal media. Total proteins extracted from cells collected during logarithmic and late stationary growth phases were analyzed by 1D liquid chromatography, followed by mass spectroscopy. The ATP citrate lyase enzyme was expressed at similar concentrations in both conditions, in both logarithmic and stationary phase, but many upstream and downstream enzymes showed drastically different expression levels. In non-lipogenic conditions, several pyruvate enzymes were expressed at higher concentration. These enzymes, especially the pyruvate decarboxylase and pyruvate dehydrogenase, may be regulating carbon flux away from central metabolism and reducing the amount of citrate being produced in the mitochondria. While crucial for the oleaginous phenotype, the constitutively expressed ATP citrate lyase appears to cleave citrate in response to carbon flux upstream from other enzymes creating the oleaginous phenotype.


Subject(s)
Gene Expression , Lipid Metabolism/genetics , Lipids/genetics , Nitrogen/metabolism , Proteome/genetics , Yarrowia/genetics , Yarrowia/metabolism , Computer Simulation , Fungal Proteins/genetics , Fungal Proteins/metabolism , Proteome/analysis , Proteomics/methods , Yarrowia/chemistry
11.
Can J Microbiol ; 67(3): 249-258, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33306436

ABSTRACT

Three bacterial species isolated from whole body extracts of the greater wax moth larvae, Galleria mellonella, were evaluated for their ability to utilize low-density polyethylene (LDPE) as a sole carbon source in vitro. These bacteria were identified as Lysinibacillus fusiformis, Bacillus aryabhattai, and Microbacterium oxydans. Their ability to biodegrade LDPE was assessed by growth curves, cell biomass production, polyethylene (PE) weight loss, and the presence of LDPE hydrolysis products in the growth media. Consortia of these bacteria with three other bacteria previously shown to degrade LDPE (Cupriavidus necator H16, Pseudomonas putida LS46, and Pseudomonas putida IRN22) were also tested. Growth curves of the bacteria utilizing LDPE as a sole carbon source revealed a peak in cell density after 24 h. Cell densities declined by 48 h but slowly increased again to different extents, depending on the bacteria. Incubation of LDPE with bacteria isolated from greater wax moth larvae had significant effects on bacterial cell mass production and weight loss of LDPE in PE-containing media. The bacterial consortia were better able to degrade LDPE than were the individual species alone. Gas chromatographic analyses revealed the presence of linear alkanes and other unknown putative LDPE hydrolysis products in some of bacterial culture media.


Subject(s)
Bacteria/metabolism , Microbial Consortia , Moths/microbiology , Polyethylene/metabolism , Animals , Bacteria/classification , Bacteria/growth & development , Bacteria/isolation & purification , Biodegradation, Environmental , Hydrolysis , Larva/microbiology
12.
Can J Microbiol ; 67(6): 476-490, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34057367

ABSTRACT

Pseudomonas chlororaphis PA23 is a biocontrol agent capable of protecting canola against the fungal pathogen Sclerotinia sclerotiorum. In addition to producing antifungal compounds, this bacterium synthesizes and accumulates polyhydroxyalkanoate (PHA) polymers as carbon and energy storage compounds. Because the role of PHA in PA23 physiology is currently unknown, we investigated the impact of this polymer on stress resistance, adherence to surfaces, and interaction with the protozoan predator Acanthamoeba castellanii. Three PHA biosynthesis mutants were created, PA23phaC1, PA23phaC1ZC2, and PA23phaC1ZC2D, which accumulated reduced PHA. Our phenotypic assays revealed that PA23phaC1ZC2D produced less phenazine (PHZ) compared with the wild type (WT) and the phaC1 and phaC1ZC2 mutants. All three mutants exhibited enhanced sensitivity to UV irradiation, starvation, heat stress, cold stress, and hydrogen peroxide. Moreover, motility, exopolysaccharide production, biofilm formation, and root attachment were increased in strains with reduced PHA levels. Interaction studies with the amoeba A. castellanii revealed that the WT and the phaC1 and phaC1ZC2 mutants were consumed less than the phaC1ZC2D mutant, likely due to decreased PHZ production by the latter. Collectively these findings indicate that PHA accumulation enhances PA23 resistance to a number of stresses in vitro, which could improve the environmental fitness of this bacterium in hostile environments.


Subject(s)
Acanthamoeba castellanii/physiology , Biofilms/growth & development , Polyhydroxyalkanoates/metabolism , Pseudomonas chlororaphis/physiology , Stress, Physiological/physiology , Bacterial Adhesion , Brassica napus/microbiology , Mutation , Phenazines/metabolism , Polyhydroxyalkanoates/genetics , Polysaccharides, Bacterial/metabolism , Pseudomonas chlororaphis/genetics , Pseudomonas chlororaphis/metabolism
13.
Can J Anaesth ; 68(11): 1690-1694, 2021 11.
Article in English | MEDLINE | ID: mdl-34291422

ABSTRACT

PURPOSE: Chronic scrotal content pain, chronic orchialgia, or testicular pain can present after trauma, vasectomy, and hernia repair, among other triggers. Microsurgical denervation of the spermatic cord is an option for definitive pain control. While this practice is established in adult urology, access to diagnostic intervention and definitive denervation surgery is limited in the pediatric population. CLINICAL FEATURES: We report a case of definitive resolution of testicular pain with microsurgical denervation of the spermatic cord in a pediatric patient with post-traumatic chronic orchialgia that significantly reduced his daily activities and worsened his anxiety prior to this treatment. The patient underwent attempts at conservative medication-based management, followed by diagnostic spermatic cord nerve block before definitive denervation surgery. CONCLUSIONS: The incidence of chronic pain in pediatrics is substantial and is estimated to be around 20%. Orchialgia remains difficult and problematic to treat. Mental health diagnoses such as anxiety and depression are also significantly associated with chronic pain. Following consideration and implementation of steps for all these concerns, a diagnostic block and microsurgical denervation led to successful resolution of chronic testicular pain in a pediatric patient.


RéSUMé: OBJECTIF: La douleur chronique au niveau du contenu scrotal, l'orchialgie chronique ou la douleur testiculaire peuvent apparaître à la suite d'un traumatisme, d'une vasectomie, et d'une réparation herniaire, entre autres déclencheurs. La dénervation microchirurgicale du cordon spermatique est une option pour le contrôle définitif de la douleur. Bien que cette pratique soit établie en urologie de l'adulte, l'accès à l'intervention diagnostique et à une chirurgie de dénervation définitive est limité pour la population pédiatrique. CARACTéRISTIQUES CLINIQUES : Nous rapportons un cas de résolution définitive d'une douleur testiculaire par dénervation microchirurgicale du cordon spermatique chez un patient pédiatrique souffrant d'orchialgie chronique post-traumatique, laquelle réduisait de manière significative ses activités quotidiennes et empirait son anxiété, avant ce traitement. Le patient a subi plusieurs tentatives de prises en charge conservatrices à l'aide de traitements médicamenteux, suivies d'un bloc nerveux diagnostique du cordon spermatique avant chirurgie de dénervation définitive. CONCLUSION: L'incidence de douleur chronique en pédiatrie est importante et est estimée à environ 20%. L'orchialgie reste difficile et problématique à traiter. Des diagnostics de santé mentale tels que l'anxiété et la dépression sont également associés de manière significative à la douleur chronique. Après examen et mise en œuvre d'étapes pour tenir compte de toutes ces préoccupations, un bloc diagnostique et une dénervation microchirurgicale ont conduit à la résolution réussie de la douleur testiculaire chronique chez un patient pédiatrique.


Subject(s)
Chronic Pain , Pediatrics , Spermatic Cord , Adult , Child , Chronic Pain/etiology , Denervation , Humans , Male , Microsurgery , Spermatic Cord/surgery
14.
Eur J Anaesthesiol ; 38(11): 1111-1123, 2021 Nov 01.
Article in English | MEDLINE | ID: mdl-33720063

ABSTRACT

BACKGROUND: Emergence delirium is a common complication in paediatric anaesthesia associated with significant morbidity. Total intravenous anaesthesia (TIVA) and intra-operative dexmedetomidine as an adjuvant to sevoflurane anaesthesia can both reduce the incidence of emergence delirium compared with sevoflurane alone, but no studies have directly compared their relative efficacy. OBJECTIVE: The study objective was to compare the effects of TIVA and dexmedetomidine on the incidence of paediatric emergence delirium. STUDY DESIGN: The current study is a systematic review and network meta-analysis (NMA) of randomised controlled trials. DATA SOURCES: We conducted a systematic search of 12 databases including Medline (Ovid) and Web of Science (Clarivate Analytics) from their respective inception to December 2020. ELIGIBILITY: Inclusion criteria were randomised controlled trials of paediatric patients undergoing general anaesthesia using sevoflurane, sevoflurane with dexmedetomidine or TIVA. Data were extracted by two reviewers according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and analysed using NMA methodology. Risk ratios and 95% credible intervals (CrI) were calculated for all outcomes [emergence delirium, postoperative nausea and vomiting (PONV), and time to emergence and extubation]. The protocol was registered with PROSPERO (CRD42018091237). RESULTS: The systematic review returned 66 eligible studies comprising 5257 patients with crude median emergence delirium incidences of 12.8, 9.1 and 40% in the dexmedetomidine with sevoflurane, TIVA and sevoflurane alone groups, respectively. NMA indicated that compared with TIVA, sevoflurane with adjuvant dexmedetomidine decreased the incidence of emergence delirium without statistical difference (risk ratio 0.88, 95% CrI 0.61 to 1.20, low quality of evidence), but resulted in a higher incidence of PONV (risk ratio: 2.3, 95% CrI 1.1 to 5.6, low quality of evidence). CONCLUSION: Clinical judgement, considering the patient's risk factors for the development of clinically significant outcomes such as emergence delirium and PONV, should be used when choosing between TIVA and sevoflurane with adjuvant dexmedetomidine. These findings are limited by the low quality of evidence (conditional recommendation).


Subject(s)
Dexmedetomidine , Emergence Delirium , Anesthesia, General , Anesthesia, Intravenous , Child , Dexmedetomidine/adverse effects , Emergence Delirium/chemically induced , Emergence Delirium/diagnosis , Emergence Delirium/epidemiology , Humans , Network Meta-Analysis , Randomized Controlled Trials as Topic
15.
Genes Dev ; 27(23): 2590-601, 2013 Dec 01.
Article in English | MEDLINE | ID: mdl-24298058

ABSTRACT

The aquaglyceroprin Fps1 is responsible for glycerol transport in yeast in response to changes in extracellular osmolarity. Control of Fps1 channel activity in response to hyperosmotic shock involves a redundant pair of regulators, Rgc1 (regulator of the glycerol channel 1) and Rgc2, and the MAPK Hog1 (high-osmolarity glycerol response 1). However, the mechanism by which these factors influence channel activity is unknown. We show that Rgc2 maintains Fps1 in the open channel state in the absence of osmotic stress by binding to its C-terminal cytoplasmic domain. This interaction involves a tripartite pleckstrin homology (PH) domain within Rgc2 and a partial PH domain within Fps1. Activation of Hog1 in response to hyperosmotic shock induces the rapid eviction of Rgc2 from Fps1 and consequent channel closure. Hog1 was recruited to the N-terminal cytoplasmic domain of Fps1, which it uses as a platform from which to multiply phosphorylate Rgc2. Thus, these results reveal the mechanism by which Hog1 regulates Fps1 in response to hyperosmotic shock.


Subject(s)
Membrane Proteins/metabolism , Mitogen-Activated Protein Kinases/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/physiology , Mitogen-Activated Protein Kinases/genetics , Mutation , Osmotic Pressure/physiology , Phosphorylation , Protein Binding , Protein Structure, Tertiary , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/genetics
16.
Can Assoc Radiol J ; 72(2): 208-214, 2021 May.
Article in English | MEDLINE | ID: mdl-33345576

ABSTRACT

BACKGROUND: The Value-Based Healthcare (VBH) concept is designed to improve individual healthcare outcomes without increasing expenditure, and is increasingly being used to determine resourcing of and reimbursement for medical services. Radiology is a major contributor to patient and societal healthcare at many levels. Despite this, some VBH models do not acknowledge radiology's central role; this may have future negative consequences for resource allocation. METHODS, FINDINGS AND INTERPRETATION: This multi-society paper, representing the views of Radiology Societies in Europe, the USA, Canada, Australia, and New Zealand, describes the place of radiology in VBH models and the health-care value contributions of radiology. Potential steps to objectify and quantify the value contributed by radiology to healthcare are outlined.


Subject(s)
Delivery of Health Care/economics , Health Care Costs , Radiology/economics , Radiology/methods , Australia , Canada , Europe , Humans , New Zealand , Societies, Medical , United States
17.
Radiology ; 294(2): 342-350, 2020 02.
Article in English | MEDLINE | ID: mdl-31891320

ABSTRACT

Background Trends in noninvasive diagnostic imaging (NDI) utilization rates have predominantly been reported in Medicare enrollees. To the authors' knowledge, there has been no prior direct comparison of utilization rates between Medicare and commercially insured patients. Purpose To analyze trends in NDI utilization rates by modality, comparing Medicare fee-for-service and commercially insured enrollees. Materials and Methods This study was a retrospective trend analysis of NDI performed between 2003 and 2016 as reported in claims databases for all adults enrolled in fee-for-service Medicare and for roughly 9 million commercially insured patients per year. The commercially insured patients were divided into two populations: those aged 18-44 years and those aged 45-64 years. The same procedure code definitions for NDI were applied to both Medicare and commercial claims, rates were calculated per 1000 enrollees, and trends were reported over time in aggregate followed by modality (CT, MRI, nuclear imaging, echocardiography, US, radiography). Join-point regression was used to model annual rates and to identify statistically significant (P < .05) changes in trends. Results In almost all instances, Medicare enrollees had the highest utilization rate for each modality, followed by commercially insured patients aged 45-64 years, then aged 18-44 years. All three populations showed utilization growth through the mid to late 2000s (images per 1000 enrollees per year for Medicare: 91 [95% confidence interval {CI}: 34, 148]; commercially insured patients aged 45-64 years: 158 [95% CI: 130, 186]; aged 18-44 years: 83 [95% CI: 69, 97]), followed by significant declining trends from the late 2000s through early 2010s (images per 1000 enrollees per year for Medicare: -301 [95% CI: -510, -92]; commercially insured patients aged 45-64 years: -54 [95% CI: -69, -39]; aged 18-44 years: -26 [95% CI: -31, -21]) coinciding with code-bundling events instituted by Medicare (CT, nuclear imaging, echocardiography). There were significant trend changes in modalities without code bundling (MRI, radiography, US), although flat trends mostly were exhibited. After the early 2010s, there were significant trend changes largely showing flat utilization growth. The notable exception was a significant trend change to renewed growth of CT imaging among commercially insured patients aged 45-64 years and Medicare enrollees after 2012, although at half the prior rate (images per 1000 enrollees per year for Medicare: 17 [95% CI: 6, 28]; commercially insured patients aged 45-64 years: 11 [95% CI: 2, 20]). Conclusion Noninvasive diagnostic imaging utilization trends among commercially insured individuals are similar to those in Medicare enrollees, although at lower rates. Earlier rapid growth has ceased and, except for CT, utilization has stabilized since the early 2010s. © RSNA, 2019 See also the editorial by Hentel and Wolk in this issue.


Subject(s)
Diagnostic Imaging/statistics & numerical data , Insurance, Health/statistics & numerical data , Medicare/statistics & numerical data , Patient Acceptance of Health Care/statistics & numerical data , Adolescent , Adult , Age Factors , Databases, Factual , Female , Humans , Male , Middle Aged , Retrospective Studies , United States , Young Adult
18.
Radiology ; 297(3): 699-707, 2020 12.
Article in English | MEDLINE | ID: mdl-32990514

ABSTRACT

Background There is a wide variation in radiation dose levels that can be used with chest CT in order to detect indeterminate pulmonary nodules. Purpose To compare the performance of lower-radiation-dose chest CT with that of routine dose in the detection of indeterminate pulmonary nodules 5 mm or greater. Materials and Methods In this retrospective study, CT projection data from 83 routine-dose chest CT examinations performed in 83 patients (120 kV, 70 quality reference mAs [QRM]) were collected between November 2013 and April 2014. Reference indeterminate pulmonary nodules were identified by two nonreader thoracic radiologists. By using validated noise insertion, five lower-dose data sets were reconstructed with filtered back projection (FBP) or iterative reconstruction (IR; 30 QRM with FBP, 10 QRM with IR, 5 QRM with FBP, 5 QRM with IR, and 2.5 QRM with IR). Three thoracic radiologists circled pulmonary nodules, rating confidence that the nodule was a 5-mm-or-greater indeterminate pulmonary nodule, and graded image quality. Analysis was performed on a per-nodule basis by using jackknife alternative free-response receiver operating characteristic figure of merit (FOM) and noninferiority limit of -0.10. Results There were 66 indeterminate pulmonary nodules (mean size, 8.6 mm ± 3.4 [standard deviation]; 21 part-solid nodules) in 42 patients (mean age, 51 years ± 17; 21 men and 21 women). Compared with the FOM for routine-dose CT (size-specific dose estimate, 6.5 mGy ± 1.8; FOM, 0.86 [95% confidence interval: 0.80, 0.91]), FOM was noninferior for all lower-dose configurations except for 2.5 QRM with IR. The sensitivity for subsolid nodules at 70 QRM was 60% (range, 48%-72%) and was significantly worse at a dose of 5 QRM and lower, whether or not IR was used (P < .05). Diagnostic image quality decreased with decreasing dose (P < .001) and was better with IR at 5 QRM (P < .05). Conclusion CT images reconstructed at dose levels down to 10 quality reference mAs (size-specific dose estimate, 0.9 mGy) had noninferior performance compared with routine dose in depicting pulmonary nodules. Iterative reconstruction improved subjective image quality but not performance at low dose levels. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by White and Kazerooni in this issue.


Subject(s)
Lung Neoplasms/diagnostic imaging , Radiation Dosage , Tomography, X-Ray Computed/methods , Case-Control Studies , Female , Humans , Male , Middle Aged , Multiple Pulmonary Nodules/diagnostic imaging , Observer Variation , Radiographic Image Interpretation, Computer-Assisted , Radiography, Thoracic , Retrospective Studies , Solitary Pulmonary Nodule/diagnostic imaging
19.
J Vasc Interv Radiol ; 31(6): 961-966, 2020 06.
Article in English | MEDLINE | ID: mdl-32376176

ABSTRACT

PURPOSE: To evaluate utilization trends in percutaneous embolization among radiologists and nonradiologist providers. MATERIALS AND METHODS: The nationwide Medicare Part B fee-for-service databases for 2005-2016 were used to evaluate percutaneous embolization codes. Six codes describing embolization procedures were reviewed. Physician providers were grouped as radiologists, vascular surgeons, cardiologists, nephrologists, other surgeons, and all others. RESULTS: The total volume of Medicare percutaneous embolization procedures increased from 20,262 in 2005 to 45,478 in 2016 (+125%). Radiologists performed 13,872 procedures in 2005 (68% of total volume) and 33,254 in 2016 (73% of total volume), a 140% increase in volume. While other specialists also increased the number of cases performed from 2005 to 2016, radiologists strongly predominated, performing 87% of arterial and 30% of venous procedures in 2016, more than any other single specialty. In 2014 and 2015, a sharp increase in venous embolization cases performed by nonradiologists preceded a sharp decrease in 2016, likely the result of complicated billing codes for venous procedures. Radiologists maintained a steady upward trend in the number of cases they performed during those years. CONCLUSIONS: The volume of percutaneous embolization procedures performed in the Medicare population increased from 2005 to 2016, reflecting a trend toward minimally invasive intervention. In 2016, radiologists performed nearly 10 times more arterial embolization procedures than the second highest specialty and more venous embolization procedures than any other single specialty.


Subject(s)
Embolization, Therapeutic/trends , Neoplasms/therapy , Practice Patterns, Physicians'/trends , Radiologists/trends , Specialization/trends , Aged , Aged, 80 and over , Cardiologists/trends , Databases, Factual , Female , Humans , Male , Medicare Part B/trends , Nephrologists/trends , Surgeons/trends , Time Factors , United States
20.
AJR Am J Roentgenol ; 215(2): 420-424, 2020 08.
Article in English | MEDLINE | ID: mdl-32452692

ABSTRACT

OBJECTIVE. The purpose of this study was to analyze recent trends in abdominal imaging utilization in the Medicare population. MATERIALS AND METHODS. Medicare Part B databases for 2004-2016 were reviewed, and all Current Procedural Terminology codes pertaining to noninvasive imaging of the abdomen and pelvis were identified. Codes were grouped into six categories: CT and CT angiography (CTA), MRI and MR angiography (MRA), ultrasound, radionuclide imaging, radiography, and gastrointestinal fluoroscopy. Annual utilization rates per 1000 Medicare beneficiaries were calculated. Medicare physician specialty codes were used to identify studies performed by radiologists versus nonradiologist physicians. Reimbursements were determined. RESULTS. Total abdominal imaging utilization decreased from 558.0 examinations per 1000 Medicare beneficiaries in 2004 to 441.9 in 2016 (-20.8%). CT and CTA examinations increased by 22.5% from 2004 to 2010, followed by a sharp drop in 2011 caused by code bundling. From 2011 to 2016, CT and CTA use increased by only 7.2%. Radiography utilization decreased from 129.6 examinations per 1000 Medicare beneficiaries in 2004 to 91.5 in 2016 (-29.4%). Radionuclide studies decreased from 14.0 to 9.5 (-32.1%), and gastrointestinal fluoroscopy decreased from 37.8 examinations to 22.5 (-40.5%). Utilization of ultrasound increased slightly (1.5%), whereas MRI and MRA utilization sharply increased on a percentage basis (81.2%). Reimbursements peaked in 2009 at $1.704 billion, dropped substantially in 2011 because of code bundling, and remained relatively stable thereafter. The radiologists' market share of abdominal imaging was approximately 87% in both 2004 and 2016. CONCLUSION. Abdominal imaging utilization rates have declined in recent years, in part due to code bundling, but also largely because of a decrease in the use of abdominal radiography, gastrointestinal fluoroscopy, and nuclear imaging. Reimbursements have also declined. This study also showed that most of the abdominal imaging was performed by radiologists.


Subject(s)
Abdomen/diagnostic imaging , Procedures and Techniques Utilization/statistics & numerical data , Diagnostic Imaging/statistics & numerical data , Humans , Medicare Part B , Time Factors , United States
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