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Bendsen Witt posted an update 2 months, 2 weeks ago
These findings provide new insights into the regulation of ATXN1 levels, present additional evidence for miRNA-mediated gene regulation via 5′ UTR binding, and raise the possibility that noncoding mutations in the ATXN1 locus may act as risk factors for yet to be discovered progressive ataxias.The nucleus accumbens shell (NAcSh) regulates emotional and motivational responses, a function mediated, in part, by integrating and prioritizing extensive glutamatergic projections from limbic and paralimbic brain regions. Each of these inputs is thought to encode unique aspects of emotional and motivational arousal. The projections do not operate alone, but rather are often activated simultaneously during motivated behaviors, during which they can interact and coordinate in shaping behavioral output. To understand the anatomic and physiological bases underlying these interprojection interactions, the current study in mice of both sexes focused on how the basolateral amygdala projection (BLAp) to the NAcSh regulates, and is regulated by, projections from the medial prefrontal cortex (mPFCp) and paraventricular nucleus of the thalamus (PVTp). Using a dual-color SynaptoTag technique combined with a backfilling spine imaging strategy, we found that all three afferent projections primarily targeted the secondaryers combined with backfilling of nucleus accumbens medium spiny neurons to reveal some unique anatomic alignments of presumed synapses from the basolateral amygdala, medial prefrontal cortex, and paraventricular nucleus of thalamus. We also used dual-rhodopsin optogenetics in brain slices, which reveal a nonlinear interaction between some, but not all, projections. These results provide compelling anatomic and physiological mechanisms through which different glutamatergic projections to the nucleus accumbens, and possibly different aspects of emotional and motivational arousal, interact with each other for final behavioral output.Genetic approaches in model organisms have consistently demonstrated that molecular traits such as gene expression are under genetic regulation, similar to clinical traits. The resulting expression quantitative trait loci (eQTL) have revolutionized our understanding of genetic regulation and identified numerous candidate genes for clinically relevant traits. More recently, these analyses have been extended to other molecular traits such as protein abundance, metabolite levels, and miRNA expression. Here, we performed global hepatic eQTL and microRNA expression quantitative trait loci (mirQTL) analysis in a population of Diversity Outbred mice fed two different diets. We identified several key features of eQTL and mirQTL, namely differences in the mode of genetic regulation (cis or trans) between mRNA and miRNA. Approximately 50% of mirQTL are regulated by a trans-acting factor, compared to ∼25% of eQTL. We note differences in the heritability of mRNA and miRNA expression and variance explained by each eQTL or mirQTL. In general, cis-acting variants affecting mRNA or miRNA expression explain more phenotypic variance than trans-acting variants. Lastly, we investigated the effect of diet on the genetic architecture of eQTL and mirQTL, highlighting the critical effects of environment on both eQTL and mirQTL. Overall, these data underscore the complex genetic regulation of two well-characterized RNA classes (mRNA and miRNA) that have critical roles in the regulation of clinical traits and disease susceptibility.
Management of contrast media allergies may lead to treatment delays in patients with acute ischemic stroke undergoing endovascular therapy. The optimal premedication strategy remains unclear. The aim of this report was to analyze our experience with emergent administration of premedication regimens before endovascular therapy.
We retrospectively reviewed prospective data for all patients undergoing endovascular therapy from 2012 to 2019 at an academic comprehensive stroke center. Records of patients with documented contrast allergy were reviewed and analyzed. Data collected included stroke risk factors and characteristics, historical contrast reaction details, premedication regimens administered, and signs or symptoms of allergic reaction developing post-endovascular therapy. Hospital arrival time to endovascular therapy was compared with that in those who did not have a history of contrast allergy.
We analyzed 1521 patients undergoing endovascular therapy; 60 (4%) had documented contrast allergies and edication en route to (or in) the neuroangiography suite, no patients experienced allergic symptoms. This pragmatic approach may be safe for patients who have documented contrast media allergies.Myalgia is a previously reported symptom in patients with COVID-19 infection; however, the presence of paraspinal myositis has not been previously reported. We report MR imaging findings of the spine obtained in a cohort of 9 patients with COVID-19 infection who presented to our hospital between March 3, 2020 and May 6, 2020. We found that 7 of 9 COVID-19 patients (78%) who underwent MR imaging of the spine had MR imaging evidence of paraspinal myositis, characterized by intramuscular edema and/or enhancement. Five of these 7 patients had a prolonged hospital course (greater than 25 days). Our knowledge of the imaging manifestations of COVID-19 infection is expanding. It is important for clinicians>a to be aware of the relatively high frequency of paraspinal myositis in this small cohort of patients with COVID-19 infection.
Although olfactory dysfunction is a common cranial nerve disorder, there are no simple objective morphometric criteria to assess olfactory dysfunction. The aim of this study was to evaluate the diagnostic performance of MR imaging morphometric parameters for detecting olfactory dysfunction.
This prospective study enrolled patients from those presenting with olfactory symptoms who underwent both an olfactory function test and MR imaging. Controls without olfactory dysfunction were recruited during the preoperative work-up for pituitary adenoma. Two independent neuroradiologists measured the olfactory bulb in 3D and assessed olfactory bulb concavity on MR imaging while blinded to the clinical data. Diagnostic performance was assessed using receiver operating characteristic curve analysis.
Sixty-four patients and 34 controls were enrolled. The patients were significantly older than the controls (mean age, 57.8 ± 11.9 years versus 47.1 ± 12.1 years;
< .001). Before age adjustment, the olfactory bulb hng the highest diagnostic performance for detecting olfactory dysfunction irrespective of age.
Hypophysitis is one of the well-known adverse effects of immune checkpoint inhibitors. Immune checkpoint inhibitor-induced hypophysitis frequently causes irreversible hypopituitarism, which requires long-term hormone replacement. Despite the high frequency and clinical significance, characteristic MR imaging findings of immune checkpoint inhibitor-induced hypophysitis have not been established. In the present study, we aimed to review and extract the MR imaging features of immune checkpoint inhibitor-induced hypophysitis.
This retrospective international multicenter study comprised 20 patients with melanoma who were being treated with immune checkpoint inhibitors and clinically diagnosed with immune checkpoint inhibitor-induced hypophysitis. Three radiologists evaluated the following MR imaging findings enlargement of the pituitary gland and stalk; homogeneity of enhancement of the pituitary gland; presence/absence of a well-defined poorly enhanced area and, if present, its location, shape, and signal intaracteristic and frequent MR imaging findings of immune checkpoint inhibitor-induced hypophysitis. They reflect fibrosis and are useful in distinguishing immune checkpoint inhibitor-induced hypophysitis from other types of hypophysitis/tumors.
It is unknown whether deceleration of brain atrophy is associated with disability improvement in patients with MS. Our aim was to investigate whether patients with MS with disability improvement develop less brain atrophy compared with those who progress in disability or remain stable.
We followed 980 patients with MS for a mean of 4.8 ± 2.4 years. Subjects were divided into 3 groups progress in disability (
= 241, 24.6%), disability improvement (
= 101, 10.3%), and stable (
= 638, 65.1%) at follow-up. Disability improvement and progress in disability were defined on the basis of the Expanded Disability Status Scale score change using standardized guidelines. Stable was defined as nonoccurrence of progress in disability or disability improvement. Normalized whole-brain volume was calculated using SIENAX on 3D T1WI, whereas the lateral ventricle was measured using NeuroSTREAM on 2D-T2-FLAIR images. The percentage brain volume change and percentage lateral ventricle volume change were calculated usingents with MS who improve in their clinical disability develop less brain atrophy across time compared with those who progress.
Internal auditory canal diverticula are focal lucencies along the anterior-inferior aspect of the internal auditory canal fundus. Studies in adults report conflicting data on the etiology and clinical relevance of this finding. We would expect a pediatric study to help elucidate the significance of internal auditory canal diverticula. TAK-901 inhibitor The primary goals of this study were to determine the temporal bone CT prevalence of diverticula among pediatric patients and to assess possible hearing loss and anatomic associations.
For this retrospective study including 283 pediatric temporal bone CTs, 4 neuroradiologists independently assessed for diverticula. Discrepancies were resolved by consensus. One neuroradiologist assessed for an enlarged vestibular aqueduct, labyrinthine dysplasia, cochlear cleft, and otospongiosis. Patient demographics, audiologic data, and pertinent clinical history were recorded. One-way analysis of variance and the Fisher exact test were used to assess possible associations between divertictomic variation. Familiarity with these findings may prevent neuroradiologists from recommending unnecessary additional testing in pediatric patients with isolated internal auditory canal diverticula.
Cellular uptake of the manganese ion, when administered as a contrast agent for MR imaging, can noninvasively highlight cellular activity and disease processes in both animals and humans. The purpose of this study was to explore the enhancement profile of manganese in patients with multiple sclerosis.
Mangafodipir is a manganese chelate that was clinically approved for MR imaging of liver lesions. We present a case series of 6 adults with multiple sclerosis who were scanned at baseline with gadolinium, then injected with mangafodipir, and followed at variable time points thereafter.
Fourteen new lesions formed during or shortly before the study, of which 10 demonstrated manganese enhancement of varying intensity, timing, and spatial pattern. One gadolinium-enhancing extra-axial mass, presumably a meningioma, also demonstrated enhancement with manganese. Most interesting, manganese enhancement was detected in lesions that formed in the days after mangafodipir injection, and this enhancement persisted for several weeks, consistent with contrast coming from intracellular uptake of manganese.