Lopezblake1486

ials are needed to evaluate epilepsy surgery targeting cortex involved in the first 3-10 seconds of ictus.Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor of the gut. GISTs are thought to arise solely from interstitial cells of Cajal (ICC), a KIT-positive population that controls gut motility. Activating gain-of-function mutations in KIT and PDGFRA are the most frequent driver events, and most of these tumors are responsive to the tyrosine kinase inhibitor imatinib. Less common drivers include mutant BRAFV600E and these tumors are resistant to imatinib. A mouse model of GIST was recently reported using Etv1, the master transcriptional regulator of ICC-intramuscular (IM) and ICC-myenteric (MY), to induce mutant Braf expression. ICC hyperplasia was observed in Etv1CreERT2 ;BrafLSL-V600E/+ mice but loss of Trp53 was required for development of GIST. We identified previously expression of the pan-ErbB negative regulator, LRIG1, in two distinct subclasses of ICC [ICC-deep muscular plexus (DMP) in small intestine and ICC-submucosal plexus (SMP) in colon] and that LRIG1 regulated their development from smooth muscle cell progenitors. Using Lrig1CreERT2 to induce BrafV600E , we observed ICC hyperplasia beyond the confines of ICC-DMP and ICC-SMP expression, suggesting smooth muscle cells as the cell-of-origin. To examine this possibility, we selectively activated BrafV600E in smooth muscle cells. Myh11CreERT2 ;BrafLSL-V600E/+ mice developed not only ICC hyperplasia but also GIST and in the absence of Trp53 disruption. In addition to providing a simpler model for mutant Braf GIST, these results provide conclusive evidence for smooth muscle cells as an alternative cell-of-origin for GIST. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Mucopolysaccharidosis type III (MPS III) or Sanfilippo disease is an orphan inherited lysosomal storage disease and one of the most common MPS subtypes. The classical presentation is an infantile-onset neurodegenerative disease characterised by intellectual regression, behavioural and sleep disturbances, loss of ambulation, and early death. Unlike other MPS, no disease-modifying therapy has yet been approved. Here, we review the numerous approaches of curative therapy developed for MPS III from historical ineffective haematopoietic stem cell transplantation and substrate reduction therapy to the promising ongoing clinical trials based on enzyme replacement therapy or adeno-associated or lentiviral vectors mediated gene therapy. Preclinical studies are presented alongside the most recent translational first-in-man trials. In addition, we present experimental research with preclinical mRNA and gene editing strategies. Lessons from animal studies and clinical trials have highlighted the importance of an early therapy before extensive neuronal loss. A disease-modifying therapy for MPS III will undoubtedly mandate development of new strategies for early diagnosis.

In this positron emission tomography (PET) study with [

C]UCB-J, we evaluated synaptic vesicle glycoprotein 2A (SV2A) binding, which is decreased in resected brain tissues from epilepsy patients, in subjects with temporal lobe epilepsy (TLE) and compared the regional binding pattern to [

F]fluorodeoxyglucose (FDG) uptake.

Twelve TLE subjects and 12 control subjects were examined. Regional [

C]UCB-J binding potential (BP

) values were estimated using the centrum semiovale as a reference region. [

F]FDG uptake in TLE subjects was quantified using mean radioactivity values. Asymmetry in outcome measures was assessed by comparison of ipsilateral and contralateral regions. Partial volume correction (PVC) with the iterative Yang algorithm was applied based on the FreeSurfer segmentation.

In 11 TLE subjects with medial temporal lobe sclerosis (MTS), the hippocampal volumetric asymmetry was 25±11%. After PVC, [

C]UCB-J BP

asymmetry indices were 37±19% in the hippocampus, with very limited asymmetry in other brain regions. Reductions in [

C]UCB-J BP

values were restricted to the sclerotic hippocampus when compared to control subjects. The corresponding asymmetry in hippocampal [

F]FDG uptake was 22±7% and correlated with that of [

C]UCB-J BP

across subjects (R

=.38). Hippocampal asymmetries in [

C]UCB-J binding were 1.7-fold larger than those of [

F]FDG uptake.

[

C]UCB-J binding is reduced in the seizure onset zone of TLE subjects with MTS. PET imaging of SV2A may be a promising biomarker approach in the presurgical selection and evaluation of TLE patients and may improve the sensitivity of molecular imaging for seizure focus detection.

[11 C]UCB-J binding is reduced in the seizure onset zone of TLE subjects with MTS. PET imaging of SV2A may be a promising biomarker approach in the presurgical selection and evaluation of TLE patients and may improve the sensitivity of molecular imaging for seizure focus detection.

Olfactory dysfunction has been well documented in individuals with temporal lobe epilepsy, but its use in presurgical planning has yet to be examined. We assessed the role of preoperative odor identification in mesial onset seizure localization utilizing stereoelectroencephalography (S-EEG) and magnetic resonance-guided laser interstitial thermal therapy (MRgLiTT) outcome.

We identified 30 patients who had typical seizures captured during S-EEG monitoring or MRgLiTT of mesial temporal structures (n=17 S-EEG, n=13 MRgLiTT); seizure onset zone was classified as unilateral mesial seizure onset, or multifocal with unilateral mesial onset and nonmesial onset. Lithocholic acid order Odor identification ability was assessed using the Sniffin' Sticks Odor Identification Test (SSOIT). Patients also completed measures of confrontation naming and auditory-verbal learning/memory using the Boston Naming Test and Hopkins Verbal Learning Test-Revised, respectively.

Overall, patients with intractable focal epilepsy exhibited poor olfactory pker to distinguish who may or may not benefit from MRgLiTT of mesial temporal structures.

Interictal olfactory dysfunction is commonly seen in patients with intractable focal epilepsy. Odor identification is a novel, noninvasive presurgical biomarker to distinguish who may or may not benefit from MRgLiTT of mesial temporal structures.