Tracheobronchial injuries are a rare but potentially life-threatening cause of respiratory insufficiency, with high mortality rates. For patients with potentially survivable tracheobronchial ...injuries, imaging in the acute setting plays a key role in demonstrating the injuries and associated complications. The radiologist can improve outcomes by understanding typical injury patterns according to injury mechanism and the influence that imaging findings may have on treatment decisions. Chest radiography and cervical and thoracic CT are the mainstays of imaging in the acute setting and in follow-up, often as part of a whole-body trauma imaging series. The authors first consider the influence of normal tracheobronchial anatomy with regard to protective features, such as cartilaginous rings. They also discuss inherent points of vulnerability, such as points of relative fixation at the carina. A framework is then provided for understanding the typical distribution and morphology of tracheobronchial injuries according to cause. This includes penetrating, iatrogenic, and blunt force mechanisms, with consideration of potential complications. The authors highlight treatment strategies that require multidisciplinary collaboration, such as ventilation, minimizing injuries, and defining optimal surgical or nonsurgical treatment.
RSNA, 2020.
Primary cilia are non-motile sensory cytoplasmic organelles that have been implicated in signal transduction, cell to cell communication, left and right pattern embryonic development, sensation of ...fluid flow, regulation of calcium levels, mechanosensation, growth factor signaling and cell cycle progression. Defects in the formation and/or function of these structures underlie a variety of human diseases such as Alström, Bardet-Biedl, Joubert, Meckel-Gruber and oral-facial-digital type 1 syndromes. The expression and function of primary cilia in cancer cells has now become a focus of attention but has not been studied in astrocytomas/glioblastomas. To begin to address this issue, we compared the structure and expression of primary cilia in a normal human astrocyte cell line with five human astrocytoma/glioblastoma cell lines.
Cultured normal human astrocytes and five human astrocytoma/glioblastoma cell lines were examined for primary cilia expression and structure using indirect immunofluorescence and electron microscopy. Monospecific antibodies were used to detect primary cilia and map the relationship between the primary cilia region and sites of endocytosis.
We show that expression of primary cilia in normal astrocytes is cell cycle related and the primary cilium extends through the cell within a unique structure which we show to be a site of endocytosis. Importantly, we document that in each of the five astrocytoma/glioblastoma cell lines fully formed primary cilia are either expressed at a very low level, are completely absent or have aberrant forms, due to incomplete ciliogenesis.
The recent discovery of the importance of primary cilia in a variety of cell functions raises the possibility that this structure may have a role in a variety of cancers. Our finding that the formation of the primary cilium is disrupted in cells derived from astrocytoma/glioblastoma tumors provides the first evidence that altered primary cilium expression and function may be part of some malignant phenotypes. Further, we provide the first evidence that ciliogenesis is not an all or none process; rather defects can arrest this process at various points, particularly at the stage subsequent to basal body association with the plasma membrane.
Purpose
Cognitive outcomes in preterm infants may be adversely affected by use of sedation and anesthetic agents. We investigated the associations between anesthetics/sedatives and full-scale ...intelligence quotient (FSIQ) measured at 36 months corrected age (CA) in very preterm infants (born < 29 weeks gestational age).
Methods
This retrospective cohort study included preterm infants born at < 29 weeks of gestation between 1 January 2006 and 31 December 2012, whose cognitive outcomes were assessed at 36 months CA. Imputed and complete case univariable and adjusted multivariable linear regressions were used to investigate the associations between FSIQ standardized to mean (standard deviation) 100 (15) and exposure to volatile anesthetics, propofol, benzodiazepines, barbiturates, and ketamine. These agents were the subject of a 2016 warning from regulatory authorities in the USA recommending caution for administration to children and pregnant women.
Results
A total of 731 infants met the inclusion criteria. Unadjusted associations were -7 (95% confidence interval CI, -10 to -4;
P
< 0.001) and -6 (95% CI, -10 to -3;
P
< 0.001) FSIQ points with exposure to warned medications using imputed and complete case analyses, respectively. Imputed and complete case adjusted associations between FSIQ and warned medications were -3 (95% CI, -7 to 0;
P
= 0.045) and -4 (95% CI, -8 to 0;
P
= 0.071) FSIQ points, respectively. Adjusted associations between volatile anesthetic exposure only and FSIQ were -3 (95% CI, -6 to 0;
P
= 0.072) and -5 (95% CI, -9 to -2;
P
= 0.004) FSIQ points using imputed and complete case data sets, respectively. FSIQ was not associated with opioid exposure.
Conclusion
Exposure of very preterm infants to anesthetics/sedatives on the United States Food and Drug Administration warning list was associated with a decrease in FSIQ points at 36 months CA. There was no association between opioid exposure and FSIQ.
Patients undergoing endovascular therapy for acute ischemic stroke may require general anesthesia to undergo the procedure. At present, there is little clinical evidence to guide the choice of ...anesthetic in this acute setting. The clinical implications of experimental studies demonstrating anesthetic neuroprotection are poorly understood. Here, the authors evaluated the impact of anesthetic treatment on neurologic outcome in experimental stroke.
Controlled studies of anesthetics in stroke using the filament occlusion model were identified in electronic databases up to December 15, 2015. The primary outcome measures, infarct volume, and neurologic deficit score were used to calculate the normalized mean difference for each comparison. Meta-analysis of normalized mean difference values provided estimates of neuroprotection and contributions of predefined factors: study quality, the timing of treatment, and the duration of ischemia.
In 80 retrieved publications anesthetic treatment reduced neurologic injury by 28% (95% CI, 24 to 32%; P < 0.0001). Internal validity was high: publication bias enhanced the effect size by 4% or less, effect size increased with study quality (P = 0.0004), and approximately 70% of studies were adequately powered. Apart from study quality, no predefined factor influenced neuroprotection. Neuroprotection failed in animals with comorbidities. Neuroprotection by anesthetics was associated with prosurvival mechanisms.
Anesthetic neuroprotection is a robust finding in studies using the filament occlusion model of ischemic stroke and should be assumed to influence outcomes in studies using this model. Neuroprotection failed in female animals and animals with comorbidities, suggesting that the results in young male animals may not reflect human stroke.
GW bodies (glycine- and tryptophan-rich cytoplasmic bodies; also known as mammalian processing (P) or Dcp-containing bodies) were described in 2002 when a human autoimmune serum was used to ...immunoscreen a HeLa expression library. Subsequently, many investigators have focused their attention on elucidating the components and functional relevance of this ribonucleoprotein (RNP)-containing cytoplasmic microdomain to cellular and molecular biology, developmental and pathological processes, and clinical practice. GW/P body components are now known to be involved in the post-transcriptional processing of messenger RNA (mRNA) through the RNA interference pathway, 5′
→
3′ mRNA degradation as well as mRNA transport and stabilization. It is currently thought that the relevant mRNA silencing and degrading factors are partitioned to these restricted cytoplasmic microdomains thus effecting post-transcriptional regulation and the prevention of accidental degradation of functional mRNA. Although much attention has focused on GW/P bodies, other cytoplasmic RNP bodies, which have highly specialized functions, interact or co-localize with components of GW/P bodies. These include neuronal transport RNP granules, stress granules, RNP-rich cytoplasmic germline granules or chromatoid bodies, sponge bodies, cytoplasmic prion protein-induced RNP granules, U bodies and TAM bodies. This review will focus on the similarities and differences of the various cytoplasmic RNP granules as an approach to understanding their functional relationships to GW/P bodies.
Interstitial lung disease (ILD) in systemic sclerosis (SSc) is a major cause of morbidity and mortality, mostly presenting as non-specific interstitial pneumonia. Little is known about the prevalence ...of pleuroparenchymal fibroelastosis (PPFE), a specific entity affecting the visceral pleura and subpleural parenchyma. We set out to estimate PPFE prevalence in two large cohorts of SSc patients and to assess its impact on survival and functional decline.A total of 359 SSc patients, derived from two referral centres in two different countries (UK and Italy), were included. The first available high-resolution computed tomography scan was independently evaluated by two radiologists blind to clinical information, to quantify ILD extent, freestanding bronchial abnormalities, and lobar percentage involvement of PPFE on a four-point categorical scale. Discordant scores were adjudicated by a third scorer. PPFE extent was further classified as limited (≤2/18) or extensive (>2/18). Results were evaluated against functional decline and mortality.The overall prevalence of PPFE in the combined SSc population was 18% (11% with extensive PPFE), with no substantial difference between the two cohorts. PPFE was significantly linked to free-standing bronchial abnormalities (61%
25% in PPFE
no PPFE; p<0.0001) and to worse survival, independently of ILD severity or short-term lung function changes (HR 1.89, 95% CI 1.10-3.25; p=0.005).In the current study, we provide an exhaustive description of PPFE prevalence and clinical impact in the largest cohort of SSc subjects published so far. PPFE presence should be carefully considered, due to its significant prognostic implications.
Diabetic polyneuropathy (DPN) is a common but irreversible neurodegenerative complication of diabetes mellitus. Here we show that features of sensory neuron damage in mice with chronic DPN may have ...altered epigenetic micro RNA (miRNA) transcriptional control. We profiled sensory neuron messenger RNA and miRNA profiles in mice with type I diabetes mellitus and findings of DPN. Diabetic sensory dorsal root ganglia neurons showed a pattern of altered messenger RNA profiles associated with upregulated cytoplasmic sites of miRNA-mediated messenger RNA processing (GW/P bodies). Dorsal root ganglia miRNA microarray identified significant changes in expression among mice with diabetes, the most prominent of which were a 39% downregulation of mmu-let-7i and a 255% increase in mmu-miR-341; both were identified in sensory neurons. To counteract these alterations, we replenished let-7i miRNA by intranasal administration; in a separate experiment, we added an anti-miR that antagonized elevated mmu-341 after 5 months of diabetes. Both approaches independently improved electrophysiologic, structural, and behavioral abnormalities without altering hyperglycemia; control sequences did not have these effects. Dissociated adult sensory neurons exposed to an exogenous mmu-let-7i mimic displayed enhanced growth and branching, indicating a trophic action. These findings identify roles for epigenetic miRNA alterations and enhanced GW/P expression in diabetic dorsal root ganglia that contribute to the complex DPN phenotype.
GW/P bodies are cytoplasmic ribonucleoprotein-rich foci involved in microRNA (miRNA)-mediated messenger RNA (mRNA) silencing and degradation. The mRNA regulatory functions within GW/P bodies are ...mediated by GW182 and its binding partner hAgo2 that bind miRNA in the RNA-induced silencing complex (RISC). To date there are no published reports of the profile of miRNA and mRNA targeted to the RISC or a comparison of the RISC-specific miRNA/mRNA profile differences in malignant and non-malignant cells.
RISC mRNA and miRNA components were profiled by microarray analysis of malignant human U-87 astrocytoma cells and its non-malignant counterpart, primary human astrocytes. Total cell RNA as well as RNA from immunoprecipitated RISC was analyzed. The novel findings were fourfold: (1) miRNAs were highly enriched in astrocyte RISC compared to U-87 astrocytoma RISC, (2) astrocytoma and primary astrocyte cells each contained unique RISC miRNA profiles as compared to their respective cellular miRNA profiles, (3) miR-195, 10b, 29b, 19b, 34a and 455-3p levels were increased and the miR-181b level was decreased in U-87 astrocytoma RISC as compared to astrocyte RISC, and (4) the RISC contained decreased levels of mRNAs in primary astrocyte and U-87 astrocytoma cells.
The observation that miR-34a and miR-195 levels were increased in the RISC of U-87 astrocytoma cells suggests an oncogenic role for these miRNAs. Differential regulation of mRNAs by specific miRNAs is evidenced by the observation that three miR34a-targeted mRNAs and two miR-195-targeted mRNAs were downregulated while one miR-195-targeted mRNA was upregulated. Biological pathway analysis of RISC mRNA components suggests that the RISC plays a pivotal role in malignancy and other conditions. This study points to the importance of the RISC and ultimately GW/P body composition and function in miRNA and mRNA deregulation in astrocytoma cells and possibly in other malignancies.
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