To determine if repeated intravenous exposures to gadolinium-based contrast agents (GBCAs) are associated with neuronal tissue deposition.
In this institutional review board-approved single-center ...study, signal intensities from T1-weighted magnetic resonance (MR) images and postmortem neuronal tissue samples from 13 patients who underwent at least four GBCA-enhanced brain MR examinations between 2000 and 2014 (contrast group) were compared with those from 10 patients who did not receive GBCA (control group). Antemortem consent was obtained from all study participants. Neuronal tissues from the dentate nuclei, pons, globus pallidus, and thalamus of these 23 deceased patients were harvested and analyzed with inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy, and light microscopy to quantify, localize, and assess the effects of gadolinium deposition. Associations between cumulative gadolinium dose, changes in T1-weighted MR signal intensity, and ICP-MS-derived tissue gadolinium concentrations were examined by using the Spearman rank correlation coefficient (ρ).
Compared with neuronal tissues of control patients, all of which demonstrated undetectable levels of gadolinium, neuronal tissues of patients from the contrast group contained 0.1-58.8 μg gadolinium per gram of tissue, in a significant dose-dependent relationship that correlated with signal intensity changes on precontrast T1-weighted MR images (ρ = 0.49-0.93). All patients in the contrast group had relatively normal renal function at the time of MR examination. Gadolinium deposition in the capillary endothelium and neural interstitium was observed only in the contrast group.
Intravenous GBCA exposure is associated with neuronal tissue deposition in the setting of relatively normal renal function. Additional studies are needed to investigate the clinical significance of these findings and the generalizability to other GBCAs. Online supplemental material is available for this article.
Purpose To determine whether gadolinium deposits in neural tissues of patients with intracranial abnormalities following intravenous gadolinium-based contrast agent (GBCA) exposure might be related ...to blood-brain barrier integrity by studying adult patients with normal brain pathologic characteristics. Materials and Methods After obtaining antemortem consent and institutional review board approval, the authors compared postmortem neuronal tissue samples from five patients who had undergone four to 18 gadolinium-enhanced magnetic resonance (MR) examinations between 2005 and 2014 (contrast group) with samples from 10 gadolinium-naive patients who had undergone at least one MR examination during their lifetime (control group). All patients in the contrast group had received gadodiamide. Neuronal tissues from the dentate nuclei, pons, globus pallidus, and thalamus were harvested and analyzed with inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy with energy-dispersive x-ray spectroscopy, and light microscopy to quantify, localize, and assess the effects of gadolinium deposition. Results Tissues from the four neuroanatomic regions of gadodiamide-exposed patients contained 0.1-19.4 μg of gadolinium per gram of tissue in a statistically significant dose-dependent relationship (globus pallidus: ρ = 0.90, P = .04). In contradistinction, patients in the control group had undetectable levels of gadolinium with ICP-MS. All patients had normal brain pathologic characteristics at autopsy. Three patients in the contrast group had borderline renal function (estimated glomerular filtration rate <45 mL/min/1.73 m
) and hepatobiliary dysfunction at MR examination. Gadolinium deposition in the contrast group was localized to the capillary endothelium and neuronal interstitium and, in two cases, within the nucleus of the cell. Conclusion Gadolinium deposition in neural tissues after GBCA administration occurs in the absence of intracranial abnormalities that might affect the permeability of the blood-brain barrier. These findings challenge current understanding of the biodistribution of these contrast agents and their safety.
RSNA, 2017.
The coronavirus pandemic has created worldwide shortages of N95 respirators. We analyzed 4 decontamination methods for effectiveness in deactivating severe acute respiratory syndrome coronavirus 2 ...virus and effect on respirator function. Our results indicate that N95 respirators can be decontaminated and reused, but the integrity of respirator fit and seal must be maintained.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mycobacterium tuberculosis (Mtb) infects one-third of the world’s population and in 2013 accounted for 1.5 million deaths. Fluoroquinolone antibacterials, which target DNA gyrase, are critical agents ...used to halt the progression from multidrug-resistant tuberculosis to extensively resistant disease; however, fluoroquinolone resistance is emerging and new ways to bypass resistance are required. To better explain known differences in fluoroquinolone action, the crystal structures of the WT Mtb DNA gyrase cleavage core and a fluoroquinolone-sensitized mutant were determined in complex with DNA and five fluoroquinolones. The structures, ranging from 2.4- to 2.6-Å resolution, show that the intrinsically low susceptibility of Mtb to fluoroquinolones correlates with a reduction in contacts to the water shell of an associated magnesium ion, which bridges fluoroquinolone–gyrase interactions. Surprisingly, the structural data revealed few differences in fluoroquinolone–enzyme contacts from drugs that have very different activities against Mtb. By contrast, a stability assay using purified components showed a clear relationship between ternary complex reversibility and inhibitory activities reported with cultured cells. Collectively, our data indicate that the stability of fluoroquinolone/DNA interactions is a major determinant of fluoroquinolone activity and that moieties that have been appended to the C7 position of different quinolone scaffolds do not take advantage of specific contacts that might be made with the enzyme. These concepts point to new approaches for developing quinolone-class compounds that have increased potency against Mtb and the ability to overcome resistance.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
To determine the effect of baseline estimated glomerular filtration rate (eGFR) on the causal association between intravenous iodinated contrast material exposure and subsequent development of acute ...kidney injury (AKI) in propensity score-matched groups of patients who underwent contrast material-enhanced or unenhanced computed tomography (CT).
This retrospective study was HIPAA compliant and institutional review board approved. All patients who underwent contrast-enhanced (contrast material group) or unenhanced (non-contrast material group) CT between 2000 and 2010 were identified and stratified according to baseline eGFR by using Kidney Disease Outcomes Quality Initiative cutoffs for chronic kidney disease into subgroups with eGFR of 90 or greater, 60-89, 30-59, and less than 30 mL/min/1.73 m(2). Propensity score generation and 1:1 matching of patients were performed in each eGFR subgroup. Incidence of AKI (serum creatinine SCr increase of ≥0.5 mg/dL ≥44.2 μmol/L above baseline) was compared in the matched subgroups by using the Fisher exact test.
A total of 12 508 propensity score-matched patients with contrast-enhanced and unenhanced scans met all inclusion criteria. In this predominantly inpatient cohort, the incidence of AKI significantly increased with decreasing baseline eGFR (P < .0001). However, this incidence was not significantly different between contrast material and non-contrast material groups in any eGFR subgroup; for the subgroup with eGFR of 90 or greater (n = 1642), odds ratio (OR) was 0.91 (95% confidence interval CI: 0.38, 2.15), P = .82; for the subgroup with eGFR of 60-89 (n = 3870), OR was 1.03 (95% CI: 0.66, 1.60), P = .99; for the subgroup with eGFR of 30-59 (n = 5510), OR was 0.94 (95% CI: 0.76, 1.18), P = .65; and for the subgroup with eGFR of less than 30 mL/min/1.73 m(2) (n = 1486), OR was 0.97 (95% CI: 0.72, 1.30), P = .89.
Diminished eGFR is associated with an increased risk of SCr-defined AKI following CT examinations. However, the risk of AKI is independent of contrast material exposure, even in patients with eGFR of less than 30 mL/min/1.73 m(2).
Our understanding of the evolutionary history of primates is undergoing continual revision due to ongoing genome sequencing efforts. Bolstered by growing fossil evidence, these data have led to ...increased acceptance of once controversial hypotheses regarding phylogenetic relationships, hybridization and introgression, and the biogeographical history of primate groups. Among these findings is a pattern of recent introgression between species within all major primate groups examined to date, though little is known about introgression deeper in time. To address this and other phylogenetic questions, here, we present new reference genome assemblies for 3 Old World monkey (OWM) species: Colobus angolensis ssp. palliatus (the black and white colobus), Macaca nemestrina (southern pig-tailed macaque), and Mandrillus leucophaeus (the drill). We combine these data with 23 additional primate genomes to estimate both the species tree and individual gene trees using thousands of loci. While our species tree is largely consistent with previous phylogenetic hypotheses, the gene trees reveal high levels of genealogical discordance associated with multiple primate radiations. We use strongly asymmetric patterns of gene tree discordance around specific branches to identify multiple instances of introgression between ancestral primate lineages. In addition, we exploit recent fossil evidence to perform fossil-calibrated molecular dating analyses across the tree. Taken together, our genome-wide data help to resolve multiple contentious sets of relationships among primates, while also providing insight into the biological processes and technical artifacts that led to the disagreements in the first place.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
T and B cell receptor loci undergo combinatorial rearrangement, generating a diverse immune receptor repertoire, which is vital for recognition of potential antigens. Here we use a multiplex PCR with ...a mixture of primers targeting the rearranged variable and joining segments to capture receptor diversity. Differential hybridization kinetics can introduce significant amplification biases that alter the composition of sequence libraries prepared by multiplex PCR. Using a synthetic immune receptor repertoire, we identify and minimize such biases and computationally remove residual bias after sequencing. We apply this method to a multiplex T cell receptor gamma sequencing assay. To demonstrate accuracy in a biological setting, we apply the method to monitor minimal residual disease in acute lymphoblastic leukaemia patients. A similar methodology can be extended to any adaptive immune locus.
To perform a systematic review and meta-analysis of controlled studies examining the incidence of acute kidney injury (AKI) and other outcomes in patients exposed to intravenous (i.v.) contrast ...medium compared with patients who underwent an imaging examination without contrast medium or were otherwise unexposed (control group).
MEDLINE, EMBASE, Scopus, and the Cochrane Library were searched for all articles published through September 2011 that contained search terms related to nephrotoxicity following intravenous contrast medium administration. Two independent reviewers identified studies in which the incidence of AKI in patients exposed to i.v. contrast medium was directly compared with the incidence of AKI in unexposed patients through analysis of changes in serum creatinine level or estimated glomerular filtration rate 48-72 hours following imaging procedures or admission. Study characteristics and outcomes of AKI, dialysis, and mortality were extracted by using a standardized protocol. Relative risk (RR) was calculated by using random-effects models and was tested in subgroups of different patient comorbidities, contrast medium types, and AKI diagnostic criteria. RR results of less than 1.00 indicated that there was a higher incidence of these outcomes in the group that did not receive contrast medium (non-contrast medium group).
Of the 1489 studies originally identified, 13 nonrandomized studies (0.9%) representing 25,950 patients met inclusion criteria. In the group that received contrast medium (contrast medium group), risk of AKI (RR = 0.79; 95% confidence interval CI: 0.62, 1.02; P = .07), death (RR = 0.95; 95% CI: 0.55, 1.67; P = .87), and dialysis (RR = 0.88; 95% CI: 0.23, 3.43; P = .85) was similar, compared with the risk of AKI in the non-contrast medium group. This pattern was observed regardless of i.v. contrast medium type, diagnostic criteria for AKI, or whether patients had diabetes mellitus or renal insufficiency.
Controlled contrast medium-induced nephropathy studies demonstrate a similar incidence of AKI, dialysis, and death between the contrast medium group and control group.
http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12121460/-/DC1.
Asexual populations experience weaker responses to natural selection, which causes deleterious mutations to accumulate over time. Additionally, stochastic loss of individuals free of deleterious ...mutations can lead to an irreversible increase in mutational load in asexuals (the "click" in Muller's Ratchet). Here we report on the genomic divergence and distribution of mutations across eight sympatric pairs of sexual and apomictic (asexual) Boechera (Brassicaceae) genotypes. We show that apomicts harbor a greater number of derived mutations than sympatric sexual genotypes. Furthermore, in phylogenetically constrained sites that are subject to contemporary purifying selection, the ancestral, conserved allele is more likely to be retained in sexuals than apomicts. These results indicate that apomictic lineages accumulate mutations at otherwise conserved sites more often than sexuals, and support the conclusion that deleterious mutation accumulation can be a powerful force in the evolution of asexual higher plants.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
To examine the association of intravenous iodinated contrast material administration with the subsequent development of post-contrast AKI (PC-AKI), emergent dialysis, and short-term mortality ...using a propensity score-adjusted analysis of a cohort of intensive care unit (ICU) patients who underwent CT examination.
Methods
All ICU patients at our institution who received a contrast-enhanced (contrast group) or unenhanced (noncontrast group) CT scan from January 2006 to December 2014 were identified. Patients were subdivided into pre-CT eGFR > 45 and eGFR ≤ 45 subsets and separately underwent propensity score analysis. Rates of KDIGO-defined AKI, dialysis, and mortality were compared between contrast and noncontrast groups. Separate analyses of eGFR ≥ 60, 30–59, and <30 subsets were also performed.
Results
A total of 6877 ICU patients (4351 contrast, 2526 noncontrast) were included in the study. Following propensity score adjustment, the rates of AKI (31 vs. 34%, OR .88 (95% CI .75–1.05),
p
= .15), dialysis (2.0 vs. 1.7%, OR 1.20 (.66–2.17),
p
= .55), and mortality (12 vs. 14%, OR .87 (.69–1.10),
p
= .23) were not significantly higher in the contrast versus noncontrast group in the matched eGFR > 45 subset. Significantly higher rates of dialysis (6.7 vs. 2.5%, OR 2.72 (1.14–6.46),
p
= .0240) were observed in the contrast versus noncontrast group in the matched eGFR ≤ 45 subset.
Conclusions
Intravenous contrast material administration was not associated with an increased risk of AKI, emergent dialysis, and short-term mortality in ICU patients with pre-CT eGFR > 45. An increased risk of dialysis was observed in patients with pre-CT eGFR ≤ 45.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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