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2,328,000 | Sarcoma Family Kinase-Dependent Pannexin-1 Activation after Cortical Spreading Depression is Mediated by NR2A-Containing Receptors. | Cortical spreading depression (CSD) is a propagating wave of depolarization followed by depression of cortical activity. CSD triggers neuroinflammation via the pannexin-1 (Panx1) channel opening, which may eventually cause migraine headaches. However, the regulatory mechanism of Panx1 is unknown. This study investigates whether sarcoma family kinases (SFK) are involved in transmitting CSD-induced Panx1 activation, which is mediated by the NR2A-containing N-methyl-D-aspartate receptor. CSD was induced by topical application of K<sup>+</sup> to cerebral cortices of rats and mouse brain slices. SFK inhibitor, PP2, or NR2A-receptor antagonist, NVP-AAM077, was perfused into contralateral cerebral ventricles (i.c.v.) of rats prior to CSD induction. Co-immunoprecipitation and Western blot were used for detecting protein interactions, and histofluorescence for addressing Panx1 activation. The results demonstrated that PP2 attenuated CSD-induced Panx1 activation in rat ipsilateral cortices. Cortical susceptibility to CSD was reduced by PP2 in rats and by TAT-Panx308 that disrupts SFK-Panx1 interaction in mouse brain slices. Furthermore, CSD promoted activated SFK coupling with Panx1 in rat ipsilateral cortices. Moreover, inhibition of NR2A by NVP-AAM077 reduced elevation of ipsilateral SFK-Panx1 interaction, Panx1 activation induced by CSD and cortical susceptibility to CSD in rats. These data suggest NR2A-regulated, SFK-dependent Panx1 activity plays an important role in migraine aura pathogenesis. |
2,328,001 | CELSR1 Promotes Neuroprotection in Cerebral Ischemic Injury Mainly Through the Wnt/PKC Signaling Pathway. | Cadherin epidermal growth factor (EGF) laminin G (LAG) seven-pass G-type receptor 1 (CELSR1) is a member of a special subgroup of adhesion G protein-coupled receptors. Although Celsr1 has been reported to be a sensitive gene for stroke, the effect of CELSR1 in ischemic stroke is still not known. Here, we investigated the effect of CELSR1 on neuroprotection, neurogenesis and angiogenesis in middle cerebral artery occlusion (MCAO) rats. The mRNA expression of Celsr1 was upregulated in the subventricular zone (SVZ), hippocampus and ischemic penumbra after cerebral ischemic injury. Knocking down the expression of <i>C</i>elsr1 in the SVZ with a lentivirus significantly reduced the proliferation of neuroblasts, the number of CD31-positive cells, motor function and rat survival and increased cell apoptosis and the infarct volume in MCAO rats. In addition, the expression of p-PKC in the SVZ and peri-infarct tissue was downregulated after ischemia/ reperfusion. Meanwhile, in the dentate gyrus of the hippocampus, knocking down the expression of <i>C</i>elsr1 significantly reduced the proliferation of neuroblasts; however, it had no influence on motor function, cell apoptosis or angiogenesis. These data indicate that CELSR1 has a neuroprotective effect on cerebral ischemia injury by reducing cell apoptosis in the peri-infarct cerebral cortex and promoting neurogenesis and angiogenesis, mainly through the Wnt/PKC pathway. |
2,328,002 | Successful Stem Cell Apheresis Using Spectra Optia in a 6 kg Child With Atypical Teratoid/Rhabdoid Tumor. | Peripheral blood stem cell apheresis has become a routine procedure for the collection of peripheral blood stem cells to enable high-dose chemotherapy followed by autologous stem cell transplantation in high-risk pediatric malignancies. However, the procedure remains challenging in very low-weight infants due to high extracorporeal blood volume and citrate toxicity. Our case report demonstrates in detail a successful and complication-free large-volume leukapheresis in a very small infant weighing 6 kg using a Spectra Optia apheresis system after placing a femoral double-lumen Shaldon catheter. Anticoagulation was achieved by citrate dextrose solution without the use of heparin. The total amount of blood being processed during the procedure equaled almost 4 times the total blood volume of the patient. The final apheresis product contained 14.0×10 CD34 cells/kg body weight. The infant was diagnosed with an atypical teratoid/rhabdoid tumor of the thalamus and third ventricle at the age of 3 months and had a history of epileptic seizures. |
2,328,003 | Expression of NFIA and NFIB within the murine spinal cord. | The Nuclear factor I proteins comprise a family of transcription factors that are expressed in many developing and mature cell populations, including within the central nervous system. Within the embryonic mouse spinal cord, NFIA and NFIB are expressed by neural progenitor cells lining the central canal, where they act to promote astrocytic and oligodendrocytic lineage specification. Cells lining the mature spinal cord central canal retain characteristics of neural progenitor cells, but the expression of NFIA and NFIB within the mature spinal cord at a cell-type-specific level remains undefined. Here, we investigated where these two transcription factors are expressed within the adult mouse spinal cord. We reveal that both factors are expressed in similar cohorts of mature cells, including ependymal cells, interneurons and motor neurons. We also show robust and widespread expression of NFIA and NFIB within nestin-expressing cells following injury to the spinal cord. Collectively, these data provide a basis to further define what functional role(s) NFIA and NFIB play within the adult spinal cord. |
2,328,004 | Repair of ventricular wall by pericranial flap: a valuable option? | Ventricular walls penetration frequently occurs in periventricular gliomas surgery. Even when aimed at maximal tumor resection, it can lead to several complications, including CSF leak, delayed wound healing and, potentially, distant tumor dissemination, with a negative impact on overall survival. Several authors have claimed damaged ventricular walls always need repair, especially when the additional use of intrathecal chemotherapy is scheduled. Fibrin sponge has been consistently used in the past to address small ventricular walls defects but more recently attention has been focused on TachoSilTM, that seems to be a valid alternative to close up to 1.5 cm gaps. After an accurate review of literature, we were unable to find any report describing the use of autologous pericranium to the same aim. We report the case of a 54 years-old patient who presented with symptoms of intracranial hypotension four weeks after his last surgery (performed at another Institution) for a relapsing right frontal grade III astrocytoma,. Pre-operative MRI showed a huge gap in the roof of the right frontal ventricular horn, associated to a large subdural hygroma and a massive subcutaneous CSF collection. The gap was repaired using a layer of autologous pericranium, sutured by pial stitches to the surrounding brain and reinforced by fibrin glue. Full and permanent leak sealing was obtained within the next 2 weeks, but patient immediately and fully recovered from his symptoms. Although limited by the single case experience, we believe that pericranium might be considered as an alternative to artificial materials in cases of large ventricular walls openings, being easily intraoperatively retrievable, granting maximal biocompatibility, not significantly impacting on surgery duration and overall costs. |
2,328,005 | Pattern recognition analysis of directional intravoxel incoherent motion MRI in ischemic rodent brains. | This study aimed to demonstrate a reliable automatic segmentation method for independently separating reduced diffusion and decreased perfusion areas in ischemic stroke brains using constrained nonnegative matrix factorization (cNMF) pattern recognition in directional intravoxel incoherent motion MRI (IVIM-MRI). First, the feasibility of cNMF-based segmentation of IVIM signals was investigated in both simulations and in vivo experiments. The cNMF analysis was independently performed for S<sub>0</sub> -normalized and scaled (by the difference between the maximum and minimum) IVIM signals, respectively. Segmentations of reduced diffusion (from S<sub>0</sub> -normalized IVIM signals) and decreased perfusion (from scaled IVIM signals) areas were performed using the corresponding cNMF pattern weight maps. Second, Monte Carlo simulations were performed for directional IVIM signals to investigate the relationship between the degree of vessel alignment and the direction of the diffusion gradient. Third, directional IVIM-MRI experiments (x, y and z diffusion-gradient directions, 20 b values at 7 T) were performed for normal (n = 4), sacrificed (n = 1, no flow) and ischemic stroke models (n = 4, locally reduced flow). The results showed that automatic segmentation of the hypoperfused lesion using cNMF analysis was more accurate than segmentation using the conventional double-exponential fitting. Consistent with the simulation, the double-exponential pattern of the IVIM signals was particularly strong in white matter and ventricle regions when the directional flows were aligned with the applied diffusion-gradient directions. cNMF analysis of directional IVIM signals allowed robust automated segmentation of white matter, ventricle, vascular and hypoperfused regions in the ischemic brain. In conclusion, directional IVIM signals were simultaneously sensitive to diffusion and aligned flow and were particularly useful for automatically segmenting ischemic lesions via cNMF-based pattern recognition. |
2,328,006 | Apolipoprotein E Facilitates Amyloid-β Oligomer-Induced Tau Phosphorylation. | Hyperphosphorylated tau is one of the key characteristics of Alzheimer's disease (AD), and tau pathology correlates with cognitive impairment in AD better than amyloid-β (Aβ) pathology. Thus, a complete understanding of the relevant factors involved in tau phosphorylation is important for AD treatment. APOEɛ4, the strongest genetic risk factor for AD, was found to be involved in tau pathology in frontotemporal dementia. This result indicated that apolipoprotein E (ApoE) may also participate in tau phosphorylation in AD. In the present study, we injected Aβ oligomer (AβO) into the lateral ventricles of wild-type (WT) mice and apoE-/- mice to test the process of tau phosphorylation in the acute phase. We found that the phosphorylated tau and phosphokinase levels were higher in WT mice than in apoE-/- mice. These phenomena were also confirmed in vitro. ApoE ɛ4-treated apoE-/- neurons exhibited more phosphorylated tau than ApoE ɛ2- and ApoE ɛ3-treated neurons. We also found that AβO induced more serious inflammation in WT mice and in ApoE-positive cultured neurons. Anti-inflammatory treatment reduced the phosphorylated tau level induced by AβOs in ApoE-positive neurons. These results suggest that ApoE may facilitate the phosphorylation of tau induced by AβO via inflammation. |
2,328,007 | Neural stem cell therapy of foetal onset hydrocephalus using the HTx rat as experimental model. | Foetal onset hydrocephalus is a disease starting early in embryonic life; in many cases it results from a cell junction pathology of neural stem (NSC) and neural progenitor (NPC) cells forming the ventricular zone (VZ) and sub-ventricular zone (SVZ) of the developing brain. This pathology results in disassembling of VZ and loss of NSC/NPC, a phenomenon known as VZ disruption. At the cerebral aqueduct, VZ disruption triggers hydrocephalus while in the telencephalon, it results in abnormal neurogenesis. This may explain why derivative surgery does not cure hydrocephalus. NSC grafting appears as a therapeutic opportunity. The present investigation was designed to find out whether this is a likely possibility. HTx rats develop hereditary hydrocephalus; 30-40% of newborns are hydrocephalic (hyHTx) while their littermates are not (nHTx). NSC/NPC from the VZ/SVZ of nHTx rats were cultured into neurospheres that were then grafted into a lateral ventricle of 1-, 2- or 7-day-old hyHTx. Once in the cerebrospinal fluid, neurospheres disassembled and the freed NSC homed at the areas of VZ disruption. A population of homed cells generated new multiciliated ependyma at the sites where the ependyma was missing due to the inherited pathology. Another population of NSC homed at the disrupted VZ differentiated into βIII-tubulin+ spherical cells likely corresponding to neuroblasts that progressed into the parenchyma. The final fate of these cells could not be established due to the protocol used to label the grafted cells. The functional outcomes of NSC grafting in hydrocephalus remain open. The present study establishes an experimental paradigm of NSC/NPC therapy of foetal onset hydrocephalus, at the etiologic level that needs to be further explored with more analytical methodologies. |
2,328,008 | Silencing of circular RNA HIPK2 in neural stem cells enhances functional recovery following ischaemic stroke. | Circular RNAs (circRNAs) have been reported to be involved in central nervous system (CNS) diseases and to have a close connection with neuronal development. However, the role of circRNAs in neural stem cell (NSC) differentiation and the treatment of ischaemic stroke remains unknown.</AbstractText>Ischaemic stroke was induced in mice using transient middle cerebral artery occlusion (tMCAO). NSCs were transducted with circHIPK2 siRNA (si-circHIPK2-NSCs) or vehicle control (si-circCon-NSCs) and microinjected into lateral ventricle of brain at 7 d post-tMCAO. Magnetic resonance imaging (MRI) was used to detect brain damage, and functional deficits were evaluated with sensorimotor behavioural tests. The distribution of the transplanted NSCs was investigated by near-infrared fluorescence imaging (NIF) and immunofluorescence. The neural plasticity of si-circHIPK2-NSCs was verified by western blot and immunofluorescence in vivo and in vitro.</AbstractText>We investigated the role of circHIPK2 in NCS differentiation. In vitro, silencing of circHIPK2 facilitated NSCs directionally differentiated to neurons but had no effect on the differentiation to astrocytes. In vivo, microinjected NSCs could migrate to the ischaemic hemisphere after stroke induction. Si-circHIPK2-NSCs increased neuronal plasticity in the ischaemic brain, conferred long-lasting neuroprotection, and significantly reduced functional deficits.</AbstractText>Si-circHIPK2 regulates NSC differentiation, and microinjection of si-circHIPK2-NSCs exhibits a promising therapeutic strategy to neuroprotection and functional recovery after stroke.</AbstractText>The National Key Research and Development Program of China; the International Cooperation and Exchange of the National Natural Science Foundation of China; the National Natural Science Foundation of China; the Jiangsu Innovation & Entrepreneurship Team Program.</AbstractText>Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.</CopyrightInformation> |
2,328,009 | Schizophrenia-related microdeletion causes defective ciliary motility and brain ventricle enlargement via microRNA-dependent mechanisms in mice. | Progressive ventricular enlargement, a key feature of several neurologic and psychiatric diseases, is mediated by unknown mechanisms. Here, using murine models of 22q11-deletion syndrome (22q11DS), which is associated with schizophrenia in humans, we found progressive enlargement of lateral and third ventricles and deceleration of ciliary beating on ependymal cells lining the ventricular walls. The cilia-beating deficit observed in brain slices and in vivo is caused by elevated levels of dopamine receptors (Drd1), which are expressed in motile cilia. Haploinsufficiency of the microRNA-processing gene Dgcr8 results in Drd1 elevation, which is brought about by a reduction in Drd1-targeting microRNAs miR-382-3p and miR-674-3p. Replenishing either microRNA in 22q11DS mice normalizes ciliary beating and ventricular size. Knocking down the microRNAs or deleting their seed sites on Drd1 mimicked the cilia-beating and ventricular deficits. These results suggest that the Dgcr8-miR-382-3p/miR-674-3p-Drd1 mechanism contributes to deceleration of ciliary motility and age-dependent ventricular enlargement in 22q11DS. |
2,328,010 | Hydrocephalus Resulting from Late-Onset Aqueductal Membranous Occlusion: A Case Report and Review of the Literature.<Pagination><StartPage>345</StartPage><EndPage>349</EndPage><MedlinePgn>345-349</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.wneu.2020.02.027</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S1878-8750(20)30292-8</ELocationID><Abstract><AbstractText Label="BACKGROUND">Late-onset aqueductal membranous occlusion (LAMO) is 1 of the few causes of noncommunicating hydrocephalus. Here, we report a case of LAMO and review the associated literature.</AbstractText><AbstractText Label="CASE DESCRIPTION">A 36-year-old man had complained of headache and loss of consciousness. Conventional magnetic resonance imaging (MRI) showed dilatation of the lateral and third ventricles but not of the fourth ventricle. Phase-contrast cine MRI confirmed cessation of cerebrospinal fluid (CSF) flow in the aqueduct of Sylvius. Sagittal and coronal turbo spin echo T2-weighted imaging with 3-dimensional driven equilibrium pulse (3D-DRIVE) revealed a membranous occlusion at the aqueduct of Sylvius and LAMO was diagnosed. The patient underwent endoscopic third ventriculostomy. Occlusion of the aqueduct of Sylvius by a thin membrane was observed and endoscopic aqueductoplasty was also conducted. The patient's symptoms were ameliorated shortly after the operation. Postoperative phase-contrast cine and 3D-DRIVE MRI showed restored CSF flow in the aqueduct of Sylvius and at the bottom of the third ventricle.</AbstractText><AbstractText Label="CONCLUSIONS">We treated a case of LAMO, which usually presents with headache as an initial symptom. 3D-DRIVE MRI is useful for detecting membranous occlusions and for evaluating pre- and postoperative CSF flow. LAMO can be cured by endoscopic third ventriculostomy and/or endoscopic aqueductoplasty.</AbstractText><CopyrightInformation>Copyright © 2020 Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Terada</LastName><ForeName>Yukinori</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurosurgery, Osaka Red Cross Hospital, Osaka, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yamamoto</LastName><ForeName>Masaya</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Neurosurgery, Osaka Red Cross Hospital, Osaka, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Motoie</LastName><ForeName>Ryota</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Neurosurgery, Osaka Red Cross Hospital, Osaka, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Matsui</LastName><ForeName>Yuya</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurosurgery, Osaka Red Cross Hospital, Osaka, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Katsuki</LastName><ForeName>Takahisa</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Neurosurgery, Osaka Red Cross Hospital, Osaka, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mori</LastName><ForeName>Nobuyuki</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Radiology, Osaka Red Cross Hospital, Osaka, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hashimoto</LastName><ForeName>Kenji</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Neurosurgery, Osaka Red Cross Hospital, Osaka, Japan. Electronic address: hashi-ken@umin.net.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>02</Month><Day>12</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>World Neurosurg</MedlineTA><NlmUniqueID>101528275</NlmUniqueID><ISSNLinking>1878-8750</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002535" MajorTopicYN="N">Cerebral Aqueduct</DescriptorName><QualifierName UI="Q000000981" MajorTopicYN="Y">diagnostic imaging</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006849" MajorTopicYN="N">Hydrocephalus</DescriptorName><QualifierName UI="Q000000981" MajorTopicYN="Y">diagnostic imaging</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D021621" MajorTopicYN="N">Imaging, Three-Dimensional</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008279" MajorTopicYN="N">Magnetic Resonance Imaging</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019028" MajorTopicYN="N">Magnetic Resonance Imaging, Cine</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D044583" MajorTopicYN="N">Neuroendoscopy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014696" MajorTopicYN="N">Ventriculostomy</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Aqueductal occlusion</Keyword><Keyword MajorTopicYN="N">Endoscopic aqueductoplasty</Keyword><Keyword MajorTopicYN="N">Endoscopic third ventriculostomy</Keyword><Keyword MajorTopicYN="N">Hydrocephalus</Keyword><Keyword MajorTopicYN="N">LAMO</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>12</Month><Day>23</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>2</Month><Day>3</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>2</Month><Day>4</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>2</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>7</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>2</Month><Day>16</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32059969</ArticleId><ArticleId IdType="doi">10.1016/j.wneu.2020.02.027</ArticleId><ArticleId IdType="pii">S1878-8750(20)30292-8</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedBookArticle><BookDocument><PMID Version="1">32119247</PMID><ArticleIdList><ArticleId IdType="bookaccession">NBK554339</ArticleId><ArticleId IdType="doi">10.1007/978-3-030-38490-6_2</ArticleId></ArticleIdList><Book><Publisher><PublisherName>Springer</PublisherName><PublisherLocation>Cham (CH)</PublisherLocation></Publisher><BookTitle book="spr9783030384906">Diseases of the Brain, Head and Neck, Spine 2020–2023: Diagnostic Imaging</BookTitle><PubDate><Year>2020</Year></PubDate><AuthorList Type="editors" CompleteYN="Y"><Author ValidYN="Y"><LastName>Hodler</LastName><ForeName>Juerg</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Radiology, University Hospital of Zürich, Zürich, Switzerland</Affiliation><Identifier Source="GRID">grid.412004.3</Identifier><Identifier Source="ISNI">0000 0004 0478 9977</Identifier></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kubik-Huch</LastName><ForeName>Rahel A.</ForeName><Initials>RA</Initials><AffiliationInfo><Affiliation>Department of Radiology, Kantonsspital Baden, Baden, Aargau, Switzerland</Affiliation><Identifier Source="GRID">grid.482962.3</Identifier><Identifier Source="ISNI">0000 0004 0508 7512</Identifier></AffiliationInfo></Author><Author ValidYN="Y"><LastName>von Schulthess</LastName><ForeName>Gustav K.</ForeName><Initials>GK</Initials><AffiliationInfo><Affiliation>Nuclear Medicine, University Hospital of Zürich, Zürich, Switzerland</Affiliation><Identifier Source="GRID">grid.412004.3</Identifier><Identifier Source="ISNI">0000 0004 0478 9977</Identifier></AffiliationInfo></Author></AuthorList><CollectionTitle book="idkdspringercollect">IDKD Springer Series</CollectionTitle><Isbn>9783030384890</Isbn><Isbn>9783030384906</Isbn><ELocationID EIdType="doi">10.1007/978-3-030-38490-6</ELocationID><Medium>Internet</Medium></Book><LocationLabel Type="chapter">Chapter 2</LocationLabel><ArticleTitle book="spr9783030384906" part="ch2">Hydrocephalus and CSF Disorders | Structural and functional neuroimaging techniques play an essential role for understanding the hydrodynamics of cerebrospinal (CSF) flow and on the comprehension of pathological processes affecting the ventricles and CSF spaces, including the different types of hydrocephalus and disorders associated with abnormal intracranial pressure. Hydrocephalus can be classified as either “obstructive and non-obstructive” or “non-communicating and communicating” based on the presence of a flow circulation abnormality inside or outside the ventricular system. Combination of different MRI sequences that provide high-resolution anatomical information and information on CSF flow provides in most cases an accurate diagnosis of the type of hydrocephalus and its causative mechanism, essential information for selecting the most adequate treatment. Different neuroimaging techniques play also an essential role in the diagnosis of other types of CSF disorders such as idiopathic intracranial hypertension and spontaneous intracranial hypotension, and in the latter condition for detecting the presence and location of CSF leaks. In this chapter, the radiological work-up and imaging features required for an accurate diagnosis of the different types of hydrocephalus and other CSF disorders will be reviewed, with the main purpose of improving our clinical practice. |
2,328,011 | Ependymoma in a dwarf goat. | Ependymomas are relatively rare neuroglial tumours that derive from ependymal cells, lining the ventricles of the brain and the central canal of the spinal cord. They occur particularly in dogs, while reports in goats are extremely scarce. A 15-year-old female dwarf goat was found in lateral recumbency, developed opisthotonus and was killed humanely. Necropsy revealed a well-demarcated, non-encapsulated mass in the diencephalon at the level of the interthalamic adhesion. Histologically, the neoplasm showed highly cellular sheets of tumour cells with occasional perivascular pseudorosettes and true rosettes. Immunohistochemistry revealed an extensive and perivascularly accentuated expression of S100 protein and glial fibrillary acidic protein, while vimentin expression was observed to a minor extent. Tumour cells were negative for cytokeratin and CNPase. Ultrastructurally, intercellular junctions were present, but cilia and blepharoblasts were lacking. The presented findings are consistent with a cellular subtype of an ependymoma. Ependymomas should be regarded as a rare cause of central nervous signs in goats.<CopyrightInformation>© Georg Thieme Verlag KG Stuttgart · New York.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kühl</LastName><ForeName>Bianca</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Pathology, University of Veterinary Medicine Hannover.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Peters</LastName><ForeName>Martin</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Chemisches und Veterinäruntersuchungsamt Westfalen.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gies</LastName><ForeName>Nicole</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Tierpark Hamm.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wohlsein</LastName><ForeName>Peter</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Pathology, University of Veterinary Medicine Hannover.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><VernacularTitle>Ependymom bei einer Zwergziege.</VernacularTitle><ArticleDate DateType="Electronic"><Year>2020</Year><Month>02</Month><Day>14</Day></ArticleDate></Article><MedlineJournalInfo><Country>Germany</Country><MedlineTA>Tierarztl Prax Ausg G Grosstiere Nutztiere</MedlineTA><NlmUniqueID>9715779</NlmUniqueID><ISSNLinking>1434-1220</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001344" MajorTopicYN="N">Autopsy</DescriptorName><QualifierName UI="Q000662" MajorTopicYN="N">veterinary</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001932" MajorTopicYN="N">Brain Neoplasms</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000648" MajorTopicYN="N">ultrastructure</QualifierName><QualifierName UI="Q000662" MajorTopicYN="Y">veterinary</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004027" MajorTopicYN="N">Diencephalon</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName><QualifierName UI="Q000648" MajorTopicYN="N">ultrastructure</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004806" MajorTopicYN="N">Ependymoma</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000648" MajorTopicYN="N">ultrastructure</QualifierName><QualifierName UI="Q000662" MajorTopicYN="Y">veterinary</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D037901" MajorTopicYN="N">Euthanasia, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015511" MajorTopicYN="N">Goat Diseases</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006041" MajorTopicYN="N">Goats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007150" MajorTopicYN="N">Immunohistochemistry</DescriptorName><QualifierName UI="Q000662" MajorTopicYN="N">veterinary</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D046529" MajorTopicYN="N">Microscopy, Electron, Transmission</DescriptorName><QualifierName UI="Q000662" MajorTopicYN="N">veterinary</QualifierName></MeshHeading></MeshHeadingList><OtherAbstract Type="Publisher" Language="ger">Ependymome sind relativ selten auftretende Tumoren ausgehend von den Ependymzellen, die die Ventrikel des Gehirns und den Zentralkanal des Rückenmarks auskleiden. Sie kommen vor allem bei Hunden vor, während Berichte über Ependymome bei Ziegen extrem selten sind. Eine 15 Jahre alte, weibliche Zwergziege wurde in Seitenlage festliegend aufgefunden, entwickelte einen Opisthotonus und wurde aufgrund der schlechten Prognose euthanasiert. Bei der Sektion fand sich eine gut abgegrenzte, nicht abgekapselte Gewebezubildung im Dienzephalon auf Höhe der interthalamischen Verbindung. Histologisch zeigte die sehr zellreiche, flächig proliferierte Neoplasie gelegentlich charakteristische perivaskuläre Pseudorosetten sowie echte Rosetten. Immunhistologisch fand sich eine deutliche, perivaskulär akzentuierte Expression von S100-Protein und saurem Gliafaserprotein, während Vimentinexpression in geringerem Ausmaß zu beobachten war. Die Tumorzellen waren negativ für Zytokeratin und CNPase. Elektronenmikroskopisch ließen sich interzelluläre Verbindungen nachweisen, allerdings gab es keine Anzeichen für Zilien und Blepharoblasten. Die Befunde decken sich mit denen des zellulären Subtyps eines Ependymoms. Ependymome sollten als seltene Ursache für zentralnervöse Symptome bei Ziegen Berücksichtigung finden. |
2,328,012 | Association of the FGFR1 mutation with spontaneous hemorrhage in low-grade gliomas in pediatric and young adult patients. | The authors aimed to investigate genetic alterations in low-grade gliomas (LGGs) in pediatric and young adult patients presenting with spontaneous hemorrhage.</AbstractText>Patients younger than 30 years of age with a pathological diagnosis of World Health Organization (WHO) grade I or II glioma and who had undergone treatment at the authors' institution were retrospectively examined. BRAF V600E, FGFR1 N546/K656, IDH1 R132, IDH2 R172, and KIAA1549-BRAF (K-B) fusion genetic alterations were identified, and the presence of spontaneous tumoral hemorrhage was recorded.</AbstractText>Among 66 patients (39 with WHO grade I and 27 with grade II tumors), genetic analysis revealed K-B fusion in 18 (27.3%), BRAF V600E mutation in 14 (21.2%), IDH1/2 mutation in 8 (12.1%), and FGFR1 mutation in 4 (6.1%). Spontaneous hemorrhage was observed in 5 patients (7.6%); 4 of them had an FGFR1 mutation and 1 had K-B fusion. Univariate analysis revealed a statistically significant association of an FGFR1 mutation and a diencephalic location with spontaneous hemorrhage. Among 19 diencephalic cases including the optic pathway, hypothalamus, and thalamus, an FGFR1 mutation was significantly associated with spontaneous hemorrhage (p < 0.001). Four FGFR1 mutation cases illustrated the following results: 1) a 2-year-old female with pilomyxoid astrocytoma (PMA) harboring the FGFR1 K656E mutation presented with intraventricular hemorrhage (IVH); 2) a 6-year-old male with PMA harboring FGFR1 K656E and D652G mutations presented with intratumoral hemorrhage (ITH); 3) a 4-year-old female with diffuse astrocytoma harboring FGFR1 K656M and D652G mutations presented with IVH; and 4) a young adult patient with pilocytic astrocytoma with the FGFR1 N546K mutation presented with delayed ITH and IVH after 7 years of observation.</AbstractText>Although the mechanism remains unclear, the FGFR1 mutation is associated with spontaneous hemorrhage in pediatric and young adult LGG.</AbstractText> |
2,328,013 | Identification of Normal Pressure Hydrocephalus by Disease-Specific Patterns of Brain Stiffness and Damping Ratio. | The aim of this study was to perform a whole-brain analysis of alterations in brain mechanical properties due to normal pressure hydrocephalus (NPH).</AbstractText>Magnetic resonance elastography (MRE) examinations were performed on 85 participants, including 44 cognitively unimpaired controls, 33 with NPH, and 8 who were amyloid-positive with Alzheimer clinical syndrome. A custom neural network inversion was used to estimate stiffness and damping ratio from patches of displacement data, accounting for edges by training the network to estimate the mechanical properties in the presence of missing data. This learned inversion was first compared with a standard analytical approach in simulation experiments and then applied to the in vivo MRE measurements. The effect of NPH on the mechanical properties was then assessed by voxel-wise modeling of the stiffness and damping ratio maps. Finally, a pattern analysis was performed on each individual's mechanical property maps by computing the correlation between each person's maps with the expected NPH effect. These features were used to fit a classifier and assess diagnostic accuracy.</AbstractText>The voxel-wise analysis of the in vivo mechanical property maps revealed a unique pattern in participants with NPH, including a concentric pattern of stiffening near the dural surface and softening near the ventricles, as well as decreased damping ratio predominantly in superior regions of the white matter (family-wise error corrected P < 0.05 at cluster level). The pattern of viscoelastic changes in each participant predicted NPH status in this cohort, separating participants with NPH from the control and the amyloid-positive with Alzheimer clinical syndrome groups, with areas under the receiver operating characteristic curve of 0.999 and 1, respectively.</AbstractText>This study provides motivation for further development of the neural network inversion framework and demonstrates the potential of MRE as a novel tool to diagnose NPH and provide a window into its pathogenesis.</AbstractText> |
2,328,014 | Different Serotypes of Adeno-Associated Virus Vector- and Lentivirus-Mediated Tropism in Choroid Plexus by Intracerebroventricular Delivery. | Regulation of gene expression by viral vectors is an effective method for researchers to explore the function of gene products in a target tissue. The choroid plexus (CP) is an important target for gene therapy of neuropsychiatric diseases such as Alzheimer's disease and major depressive disorder. However, viral tropism in CP has not been well studied as a result of limited viral vector applications. To identify CP-specific viral vectors, we intracerebroventricularly administered six different serotypes of adeno-associated virus (AAV) vectors (AAV2/1, AAV2/5, AAV2/8, AAV2/9, AAV2-BR1, and AAV2-PHP.eB) and lentivirus in adult mice. Tropism in CP was compared among these viruses. We found that AAV2/5 and AAV2/8 displayed remarkable infections in CP, while AAV2/1 infected both ependymal cells and cells in the CP. Except for the low infection intensity of AAV2/9 and lentivirus in the CP, no infection intensity was found for CP tissues injected with AAV2-BR1 or AAV2-PHP.eB. Green fluorescence protein expression in the CP after AAV2/5 infection was confirmed by Western blotting. AAV2/5-mediated tropism in epithelial cells of the CP was verified by immunostaining with transthyretin. In this study, we identified for the first time that serotype-specific AAVs 5 and 8 may be robust research tools for intracerebroventricular gene delivery. |
2,328,015 | Clinical features and genetic characteristics of hereditary diffuse leukoencephalopathy with spheroids due to CSF1R mutation: a case report and literature review. | Hereditary diffuse leukoencephalopathy with spheroid (HDLS) is an autosomal dominant white matter disease characterized by adult-onset cognitive impairment, behavioral or emotional changes, paresis, Parkinsonism, and seizures. Mutations in the gene encoding colony-stimulating factor 1 receptor (CSF1R) have been identified as the cause of HDLS.</AbstractText>Detail medical history, clinical features and brain imaging of a patient with adult-onset leukoencephalopathy, cognitive impairment and motor dysfunction was reviewed and next generation sequencing was performed. An extensive literature research was then performed to identify all patients with HDLS previously reported. The clinical characteristics, brain imaging and genetic features of patients with HDLS were reviewed.</AbstractText>A novel CSF1R mutation, c.1952G>A p.G651E was identified in the patient. Extensive review showed that HDLS typically presents with broad phenotypic variability. The most common symptoms of HDLS were cognitive impairment, followed by psychiatric symptoms, Parkinsonism, gait disorder, and dysphagia. The most common brain imaging findings of HDLS were bilateral white matter lesion, mostly around the ventricles, frontal lobe, and parietal lobe. Calcifications in white matter on CT, cerebral atrophy and thinning of corpus callosum were also common features. Although HDLS demonstrates an autosomal dominant pattern, sporadic cases are not uncommon.</AbstractText>Early recognition of clinical and neuroradiographical characteristics of HDLS is key for the correct diagnosis of the disease.</AbstractText>2020 Annals of Translational Medicine. All rights reserved.</CopyrightInformation> |
2,328,016 | Reperfusion using lactate Ringer's mixture partially eliminates IGF II receptor involved cardiac damage caused by hemorrhagic shock in diabetic rats. | Diabetes is a metabolic disorder that damages many organs. We investigated the effects of reperfusion using lactate Ringer's solution (LR) in a diabetic animal model. Eight-week-old rats were divided into groups: control, hemorrhagic shock induced (HS), diabetes mellitus (DM), DM plus HS (DM + HS) and DM rats that received LR after HS (DM + HS + LR). HS was induced by withdrawing blood from the femoral artery and arterial pressure was maintained at 40 mm Hg for 1 h. Animals were perfused with either withdrawn blood or LR. Rats were sacrificed and hearts were collected from all groups. Histopathological studies were performed using left ventricles and western blotting analysis was performed using protein extracted from the left ventricle. Using the TUNEL assay, we found more apoptotic cells in the DM + HS group compared to the control group, whereas in animals resuscitated with LR, the number of apoptotic cells was reduced. Western blotting showed a significant reduction in apoptotic markers, cyt <i>c</i>, cas 9 and cas 3, and increased survival markers, pPI3K and pAKT, in the DM + HS + LR group. Reperfusion with LR may have therapeutic effects on trauma induced HS by blocking the IGF II R facilitated apoptosis pathway in diabetic rats. |
2,328,017 | Activation of metabotropic glutamate receptor 4 regulates proliferation and neural differentiation in neural stem/progenitor cells of the rat subventricular zone and increases phosphatase and tensin homolog protein expression. | Neural stem/progenitor cells (NSPCs) persist in the mammalian subventricular zone throughout life, where they can be activated in response to physiological and pathophysiological stimuli. A recent study indicates metabotropic glutamate receptor 4 (mGluR4) is involved in regulating NSPCs behaviors. Therefore, defining mGluR4 function in NSPCs is necessary for determining novel strategies to enhance the intrinsic potential for brain regeneration after injuries. In this study, mGluR4 was functionally expressed in SVZ-derived NSPCs from male Sprague-Dawley rats, in which the cyclic adenosine monophosphate concentration was reduced after treatment with the mGluR4-specific agonist VU0155041. Additionally, lateral ventricle injection of VU0155041 significantly decreased 5-bromo-2'-deoxyuridine (BrdU)<sup>+</sup> and Ki67<sup>+</sup> cells, while increased Doublecortin (DCX)/BrdU double-positive cells in SVZ. In cultured NSPCs, mGluR4 activation decreased the ratio of BrdU<sup>+</sup> cells, G2/M-phase cells, and inhibited Cyclin D1 expression, whereas it increased neuron-specific class III β-tubulin (Tuj1) expression and the number of Tuj1, DCX, and PSA-NCAM-positive cells. However, pharmacological blocking mGluR4 with the antagonist MSOP or knockdown of mGluR4 abolished the effects of VU0155041 on NSPCs proliferation and neuronal differentiation. Further investigation demonstrated that VU0155041 treatment down-regulated AKT phosphorylation and up-regulated expression of the phosphatase and tensin homolog protein (PTEN) in NSPCs culture. Moreover VU0155041-induced proliferating inhibition and neuronal differentiating amplification in NSPCs were significantly hampered by VO-OHpic, a PTEN inhibitor. We conclude that activation of mGluR4 in SVZ-derived NSPCs suppresses proliferation and enhances their neuronal differentiation, and regulation of PTEN may be involved as a potential intracellular target of mGluR4 signal. Cover Image for this issue: https://doi.org/10.1111/jnc.15052. |
2,328,018 | Effect of combined extracts of aged garlic, ginger, and chili peppers on cognitive performance and brain antioxidant markers in Aβ-induced rats. | A combination of aged garlic, ginger, and chili peppers extracts (AGC) was studied by high-performance liquid chromatography, 2,2-diphenyl-1-picrylhydrazyl, and ferric-reducing antioxidant assays, and oxidative stress markers were analyzed in Aβ1-42-induced rats. The AGC was orally administered to Wistar rats at doses of 125, 250, and 500 mg/kg body weight (AGC125, AGC250, AGC500, respectively) for 64 days. At day 56, Aβ1-42 was injected via both sides of the lateral ventricles. The effects of the AGC on spatial and recognition memory were examined using a Morris water maze and novel object recognition tasks. Rats induced with Aβ1-42 exhibited obvious cognitive deficits, as demonstrated by their increased escape latency time (ET) and decreased retention time (RT) and percentage of discriminative index (DI). When compared with the control group, all AGC-treated rats showed significantly shorter ETs and higher DIs during the 5-min delay testing phase. Rats treated with AGC250 also had significantly longer RTs. Administration of Aβ1-42 significantly increased malondialdehyde (MDA) levels and decreased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels in the rat brain homogenate. Pretreatment with the AGC caused significant increases in SOD, GPx, and CAT activities, as well as a significant decrease in MDA in the rat brain homogenates after Aβ-induced neurotoxicity. Our results suggested that an AGC may ameliorate cognitive dysfunction in Aβ-treated rats due to its role in the upregulation of SOD, GPx, and CAT. |
2,328,019 | Parkinson's disease, aging and adult neurogenesis: Wnt/β-catenin signalling as the key to unlock the mystery of endogenous brain repair. | A common hallmark of age-dependent neurodegenerative diseases is an impairment of adult neurogenesis. Wingless-type mouse mammary tumor virus integration site (Wnt)/β-catenin (WβC) signalling is a vital pathway for dopaminergic (DAergic) neurogenesis and an essential signalling system during embryonic development and aging, the most critical risk factor for Parkinson's disease (PD). To date, there is no known cause or cure for PD. Here we focus on the potential to reawaken the impaired neurogenic niches to rejuvenate and repair the aged PD brain. Specifically, we highlight WβC-signalling in the plasticity of the subventricular zone (SVZ), the largest germinal region in the mature brain innervated by nigrostriatal DAergic terminals, and the mesencephalic aqueduct-periventricular region (Aq-PVR) Wnt-sensitive niche, which is in proximity to the SNpc and harbors neural stem progenitor cells (NSCs) with DAergic potential. The hallmark of the WβC pathway is the cytosolic accumulation of β-catenin, which enters the nucleus and associates with T cell factor/lymphoid enhancer binding factor (TCF/LEF) transcription factors, leading to the transcription of Wnt target genes. Here, we underscore the dynamic interplay between DAergic innervation and astroglial-derived factors regulating WβC-dependent transcription of key genes orchestrating NSC proliferation, survival, migration and differentiation. Aging, inflammation and oxidative stress synergize with neurotoxin exposure in "turning off" the WβC neurogenic switch via down-regulation of the nuclear factor erythroid-2-related factor 2/Wnt-regulated signalosome, a key player in the maintenance of antioxidant self-defense mechanisms and NSC homeostasis. Harnessing WβC-signalling in the aged PD brain can thus restore neurogenesis, rejuvenate the microenvironment, and promote neurorescue and regeneration. |
2,328,020 | Factors Associated with Recurrence in Takotsubo Syndrome: A Systematic Review. | Takotsubo syndrome (TTS) is characterized by a temporary systolic dysfunction of the left ventricle (LV) related to a stressful event. However, the factors associated with its recurrence are still not well established.</AbstractText>To analyze the main factors associated with TTS recurrence.</AbstractText>A systematic review was performed using the PRISMA model. Observational studies, published between January 2008 and October 2017, which presented a recurrence rate of at least 3% and/or 5 or more patients with recurrence, and who met at least 80% of the STROBE criteria were included.</AbstractText>six articles reached the criteria to compose this systematic review. The recurrence rate ranged from 1 to 3.5% per year (global recurrence rate 3.8%). One study associated higher recurrence rate with the female gender, four reported the time between the first and second episodes, one study associated body mass index (BMI) and hypercontractility of the LV middle anterior wall to a higher recurrence rate. No association between recurrence and electrocardiographic changes were determined. Beta-blockers use was not associated with recurrence rates.</AbstractText>Female gender, time from the first episode of the syndrome, low BMI and midventricular obstruction were reported as potential predictors of TTS recurrence.</AbstractText> |
2,328,021 | Emergence and Developmental Roles of the Cerebrospinal Fluid System. | We summarize recent work illuminating how cerebrospinal fluid (CSF) regulates brain function. More than a protective fluid cushion and sink for waste, the CSF is an integral CNS component with dynamic and diverse roles emerging in parallel with the developing CNS. This review examines the current understanding about early CSF and its maturation and roles during CNS development and discusses open questions in the field. We focus on developmental changes in the ventricular system and CSF sources (including neural progenitors and choroid plexus). We also discuss concepts related to the development of fluid dynamics including flow, perivascular transport, drainage, and barriers. |
2,328,022 | Regional differences in the ependyma of the optic tectal ventricle of adult zebrafish with structures referring to brain hydrodynamics. | Classical electron microscopic morphological studies provide detailed ultrastructural information, which may lend insights into cellular functions. As a follow-up to our morphological investigation of the adult zebrafish (Danio rerio) optic tectum, in this study, we have analyzed the ependymal structures lining the surfaces of the tectal ventricle: the torus, tegmental surface of the valvula cerebelli and the periventricular gray zone of the optic tectal cortex. We used toluidine blue stained plastic (semithin) sections for light microscopy and scanning electron microscopy. Our morphological findings of gated entrances and/or egresses indicate that, at least in the adult zebrafish brain, there may be a bidirectional direct flow communication between the ventricular cerebrospinal fluid and the parenchymal interstitial fluid. |
2,328,023 | International standards for fetal brain structures based on serial ultrasound measurements from Fetal Growth Longitudinal Study of INTERGROWTH-21<sup>st</sup> Project. | To create prescriptive growth standards for five fetal brain structures, measured using ultrasound, in healthy, well-nourished women at low risk of impaired fetal growth and poor perinatal outcome, taking part in the Fetal Growth Longitudinal Study (FGLS) of the INTERGROWTH-21st</sup> Project.</AbstractText>This was a complementary analysis of a large, population-based, multicenter, longitudinal study. The sample analyzed was selected randomly from the overall FGLS population, ensuring an equal distribution among the eight diverse participating sites and of three-dimensional (3D) ultrasound volumes across pregnancy (range: 15-36 weeks' gestation). We measured, in planes reconstructed from 3D ultrasound volumes of the fetal head at different timepoints in pregnancy, the size of the parieto-occipital fissure (POF), Sylvian fissure (SF), anterior horn of the lateral ventricle, atrium of the posterior horn of the lateral ventricle (PV) and cisterna magna (CM). Fractional polynomials were used to construct the standards. Growth and development of the infants were assessed at 1 and 2 years of age to confirm their adequacy for constructing international standards.</AbstractText>From the entire FGLS cohort of 4321 women, 451 (10.4%) were selected at random. After exclusions, 3D ultrasound volumes from 442 fetuses born without a congenital malformation were used to create the charts. The fetal brain structures of interest were identified in 90% of cases. All structures, except the PV, showed increasing size with gestational age, and the size of the POF, SF, PV and CM showed increasing variability. The 3rd</sup> , 5th</sup> , 50th</sup> , 95th</sup> and 97th</sup> smoothed centiles are presented. The 5th</sup> centiles for the POF and SF were 3.1 mm and 4.7 mm at 22 weeks' gestation and 4.6 mm and 9.9 mm at 32 weeks, respectively. The 95th</sup> centiles for the PV and CM were 8.5 mm and 7.5 mm at 22 weeks and 8.6 mm and 9.5 mm at 32 weeks, respectively.</AbstractText>We have produced prescriptive size standards for fetal brain structures based on prospectively enrolled pregnancies at low risk of abnormal outcome. We recommend these as international standards for the assessment of measurements obtained using ultrasound from fetal brain structures. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.</AbstractText>© 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.</CopyrightInformation> |
2,328,024 | Choroid plexus LAT2 and SNAT3 as partners in CSF amino acid homeostasis maintenance. | Cerebrospinal fluid (CSF) is mainly produced by the choroid plexus (CP) located in brain ventricles. Although derived from blood plasma, it is nearly protein-free (~ 250-fold less) and contains about 2-20-fold less free amino acids, with the exception of glutamine (Gln) which is nearly equal. The aim of this study was to determine which amino acid transporters are expressed in mouse CP epithelium in order to gain understanding about how this barrier maintains the observed amino acid concentration gradient.</AbstractText>Expression of amino acid transporters was assessed in isolated choroid plexuses (CPs) by qRT-PCR followed by localization studies using immunofluorescence with specific antibodies. The impact of LAT2 (Slc7a8) antiporter deletion on CSF amino acids was determined.</AbstractText>The purity of isolated choroid plexuses was tested on the mRNA level using specific markers, in particular transthyretin (Ttr) that was enriched 330-fold in CP compared to cerebral tissue. In a first experimental round, 14 out of 32 Slc amino acid transporters tested on the mRNA level by qPCR were selected for further investigation. Out of these, five were considered highly expressed, SNAT1 (Slc38a1), SNAT3 (Slc38a3), LAT2 (Slc7a8), ASC1 (Slc7a10) and SIT1 (Slc6a20b). Three of them were visualized by immunofluorescence: SNAT1 (Slc38a1), a neutral amino acid-Na+</sup> symporter, found at the blood side basolateral membrane of CP epithelium, while SNAT3 (Slc38a3), an amino acid-Na+</sup> symporter and H+</sup> antiporter, as well as LAT2 (Slc7a8), a neutral amino acid antiporter, were localized at the CSF-facing luminal membrane. In a LAT2 knock-out mouse model, CSF Gln was unchanged, whereas other amino acids normally 2-20-fold lower than in plasma, were increased, in particular the LAT2 uptake substrates leucine (Leu), valine (Val) and tryptophan (Trp) and some other amino acids such as glutamate (Glu), glycine (Gly) and proline (Pro).</AbstractText>These results suggest that Gln is actively transported by SNAT1 from the blood into CP epithelial cells and then released luminally into CSF via SNAT3 and LAT2. Its efflux via LAT2 may drive the reuptake from the CSF of essential amino acid substrates of this antiporter and thereby participates to maintaining the amino acid gradient between plasma and CSF.</AbstractText> |
2,328,025 | Aquaporin 1 and the Na<sup>+</sup>/K<sup>+</sup>/2Cl<sup>-</sup> cotransporter 1 are present in the leptomeningeal vasculature of the adult rodent central nervous system. | The classical view of cerebrospinal fluid (CSF) production posits the choroid plexus as its major source. Although previous studies indicate that part of CSF production occurs in the subarachnoid space (SAS), the mechanisms underlying extra-choroidal CSF production remain elusive. We here investigated the distributions of aquaporin 1 (AQP1) and Na+</sup>/K+</sup>/2Cl-</sup> cotransporter 1 (NKCC1), key proteins for choroidal CSF production, in the adult rodent brain and spinal cord.</AbstractText>We have accessed AQP1 distribution in the intact brain using uDISCO tissue clearing technique and by Western blot. AQP1 and NKCC1 cellular localization were accessed by immunohistochemistry in brain and spinal cord obtained from adult rodents. Imaging was performed using light-sheet, confocal and bright field light microscopy.</AbstractText>We determined that AQP1 is widely distributed in the leptomeningeal vasculature of the intact brain and that its glycosylated isoform is the most prominent in different brain regions. Moreover, AQP1 and NKCC1 show specific distributions in the smooth muscle cell layer of penetrating arterioles and veins in the brain and spinal cord, and in the endothelia of capillaries and venules, restricted to the SAS vasculature.</AbstractText>Our results shed light on the molecular framework that may underlie extra-choroidal CSF production and we propose that AQP1 and NKCC1 within the leptomeningeal vasculature, specifically at the capillary level, are poised to play a role in CSF production throughout the central nervous system.</AbstractText> |
2,328,026 | Are familial colloid cysts of the third ventricle associated with a worse clinical course than sporadic forms? | The incidence of asymptomatic colloid cysts is increasing due to the widespread use of neuroimaging tools. According to previous works, familial forms (within first-degree relatives) represent 5-25% of the cases, and it is not clear whether they display specific features influencing the clinical behavior of the disease.</AbstractText>We reviewed the literature to extract data from papers dealing with familial colloid cysts. For comparison, previous series dealing with the natural history of sporadic cases were identified. Also, we present two more cases of familiar colloid cysts from our experience.</AbstractText>Fifty-one patients (23 reports, plus our cases) were analyzed from the literature. Familial cases showed a younger age at diagnosis (P=0.02) and fewer asymptomatic cases (P<0.001) compared to non-familial colloid cysts. The odds ratio and relative risk of needing surgery with a positive family history for surgical cyst removal were respectively 17.5 (CI: 1.6-197.4) and 1.9 (CI: 0.71 - 5.1). Screening of other family members identified further colloid cysts in 4% of families.</AbstractText>Familial colloid cysts show a higher percentage of younger and symptomatic patients compared to non-familiar forms. A positive family history for surgical evacuation is a predictor for a similar outcome. This could indicate a predisposition to an earlier formation and faster growth, and the need for a stricter follow-up in asymptomatic patients. If confirmed in the future, this could suggest a review of the criteria for cyst treatment and extend the surgical indication to asymptomatic familial cases.</AbstractText> |
2,328,027 | Defining and expanding the phenotype of <i>QARS</i>-associated developmental epileptic encephalopathy. | The study is aimed at widening the clinical and genetic spectrum and at assessing genotype-phenotype associations in QARS</i> encephalopathy.</AbstractText>Through diagnostic gene panel screening in an epilepsy cohort, and recruiting through GeneMatcher and our international network, we collected 10 patients with biallelic QARS</i> variants. In addition, we collected data on 12 patients described in the literature to further delineate the associated phenotype in a total cohort of 22 patients. Computer modeling was used to assess changes on protein folding.</AbstractText>Biallelic pathogenic variants in QARS</i> cause a triad of progressive microcephaly, moderate to severe developmental delay, and early-onset epilepsy. Microcephaly was present at birth in 65%, and in all patients at follow-up. Moderate (14%) or severe (73%) developmental delay was characteristic, with no achievement of sitting (85%), walking (86%), or talking (90%). Additional features included irritability (91%), hypertonia/spasticity (75%), hypotonia (83%), stereotypic movements (75%), and short stature (56%). Seventy-nine percent had pharmacoresistant epilepsy with mainly neonatal onset. Characteristic cranial MRI findings include early-onset progressive atrophy of cerebral cortex (89%) and cerebellum (61%), enlargement of ventricles (95%), and age-dependent delayed myelination (88%). A small subset of patients displayed a less severe phenotype.</AbstractText>These data revealed first genotype-phenotype associations and may serve for improved interpretation of new QARS</i> variants and well-founded genetic counseling.</AbstractText>Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.</CopyrightInformation> |
2,328,028 | Autophagy Activation in Zebrafish Heart Regeneration. | Autophagy is an evolutionarily conserved process that plays a key role in the maintenance of overall cellular health. While it has been suggested that autophagy may elicit cardioprotective and pro-survival modulating functions, excessive activation of autophagy can also be detrimental. In this regard, the zebrafish is considered a hallmark model for vertebrate regeneration, since contrary to adult mammals, it is able to faithfully regenerate cardiac tissue. Interestingly, the role that autophagy may play in zebrafish heart regeneration has not been studied yet. In the present work, we hypothesize that, in the context of a well-established injury model of ventricular apex resection, autophagy plays a critical role during cardiac regeneration and its regulation can directly affect the zebrafish regenerative potential. We studied the autophagy events occurring upon injury using electron microscopy, in vivo tracking of autophagy markers, and protein analysis. Additionally, using pharmacological tools, we investigated how rapamycin, an inducer of autophagy, affects regeneration relevant processes. Our results show that a tightly regulated autophagic response is triggered upon injury and during the early stages of the regeneration process. Furthermore, treatment with rapamycin caused an impairment in the cardiac regeneration outcome. These findings are reminiscent of the pathophysiological description of an injured human heart and hence put forward the zebrafish as a model to study the poorly understood double-sword effect that autophagy has in cardiac homeostasis. |
2,328,029 | Prenatal diagnosis of mosaic trisomy 8 by amniocentesis in a fetus with ventriculomegaly and dysgenesis of the corpus callosum. | We present prenatal diagnosis of mosaic trisomy 8 by amniocentesis in a fetus with central nervous system abnormalities.</AbstractText>A 39-year-old woman was found to have fetal bilateral ventriculomegaly and enlargement of the third ventricle on prenatal ultrasound at 32 weeks of gestation. Fetal magnetic resonance imaging examination confirmed bilateral ventriculomegaly and dysgenesis of the corpus callosum. Amniocentesis was performed subsequently. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniotic cells revealed trisomy 8 mosaicism with a result of arr [GRCh37] (8) × 3[0.19], (X,Y) × 1. Conventional cytogenetic analysis on cultured amniocytes showed that among 108 cells in 12 colonies of three cultures, only one cell was abnormal with trisomy 8, trisomy 9 and monosomy 13, while the rest 107 cells had a normal karyotype. Repeat amniocentesis and cord blood sampling revealed a result of arr 8p23.3q24.3 (191,530-146,280,020) × 2.3 with a log2</sub> ratio of 0.2 compatible with 20-30% mosaicism for trisomy 8 on the uncultured amniocytes, and a result of arr 8p23.3q24.3 (191,530-146,280,020) × 2.1 with a log2</sub> ratio of 0.08 compatible with <10% mosaicism for trisomy 8 on the cord blood lymphocytes. Polymorphic DNA marker analysis excluded uniparental disomy 8. A malformed 2440-g dead fetus was delivered at 34 weeks of gestation with facial dysmorphism.</AbstractText>Cytogenetic discrepancy can occur between cultured and uncultured amniocytes in mosaic trisomy 8 at amniocentesis. aCGH analysis on uncultured amniocytes is useful for confirmation of mosaic trisomy 8 at amniocentesis. Fetuses with low-level mosaicism for trisomy 8 may prenatally present ventriculomegaly and dysgenesis of the corpus callosum.</AbstractText>Copyright © 2020. Published by Elsevier B.V.</CopyrightInformation> |
2,328,030 | Familial Dilated Cardiomyopathy Associated With a Novel Combination of Compound Heterozygous <i>TNNC1</i> Variants. | Familial dilated cardiomyopathy (DCM), clinically characterized by enlargement and dysfunction of one or both ventricles of the heart, can be caused by variants in sarcomeric genes including <i>TNNC1</i> (encoding cardiac troponin C, cTnC). Here, we report the case of two siblings with severe, early onset DCM who were found to have compound heterozygous variants in <i>TNNC1</i>: p.Asp145Glu (D145E) and p.Asp132Asn (D132N), which were inherited from the parents. We began our investigation with CRISPR/Cas9 knockout of <i>TNNC1</i> in <i>Xenopus tropicalis</i>, which resulted in a cardiac phenotype in tadpoles consistent with DCM. Despite multiple maneuvers, we were unable to rescue the tadpole hearts with either human cTnC wild-type or patient variants to investigate the cardiomyopathy phenotype <i>in vivo</i>. We therefore utilized porcine permeabilized cardiac muscle preparations (CMPs) reconstituted with either wild-type or patient variant forms of cTnC to examine effects of the patient variants on contractile function. Incorporation of 50% WT/50% D145E into CMPs increased Ca<sup>2+</sup> sensitivity of isometric force, consistent with prior studies. In contrast, incorporation of 50% WT/50% D132N, which had not been previously reported, decreased Ca<sup>2+</sup> sensitivity of isometric force. CMPs reconstituted 50-50% with both variants mirrored WT in regard to myofilament Ca<sup>2+</sup> responsiveness. Sinusoidal stiffness (SS) (0.2% peak-to-peak) and the kinetics of tension redevelopment (<i>k</i> <sub>TR</sub>) at saturating Ca<sup>2+</sup> were similar to WT for all preparations. Modeling of Ca<sup>2+</sup>-dependence of <i>k</i> <sub>TR</sub> support the observation from Ca<sup>2+</sup> responsiveness of steady-state isometric force, that the effects on each mutant (50% WT/50% mutant) were greater than the combination of the two mutants (50% D132N/50% D145E). Further studies are needed to ascertain the mechanism(s) of these variants. |
2,328,031 | Complex Interaction Between Low-Frequency APD Oscillations and Beat-to-Beat APD Variability in Humans Is Governed by the Sympathetic Nervous System. | Recent clinical, experimental and modeling studies link oscillations of ventricular repolarization in the low frequency (LF) (approx. 0.1 Hz) to arrhythmogenesis. Sympathetic provocation has been shown to enhance both LF oscillations of action potential duration (APD) and beat-to-beat variability (BVR) in humans. We hypothesized that beta-adrenergic blockade would reduce LF oscillations of APD and BVR of APD in humans and that the two processes might be linked.</AbstractText>Twelve patients with normal ventricles were studied during routine electrophysiological procedures. Activation-recovery intervals (ARI) as a conventional surrogate for APD were recorded from 10 left and 10 right ventricular endocardial sites before and after acute beta-adrenergic adrenergic blockade. Cycle length was maintained constant with right ventricular pacing. Oscillatory behavior of ARI was quantified by spectral analysis and BVR as the short-term variability. Beta-adrenergic blockade reduced LF ARI oscillations (8.6 ± 4.5 ms2</sup> vs. 5.5 ± 3.5 ms2</sup>, p</i> = 0.027). A significant correlation was present between the initial control values and reduction seen following beta-adrenergic blockade in LF ARI (r</i> s</sub> = 0.62, p</i> = 0.037) such that when initial values are high the effect is greater. A similar relationship was also seen in the beat-to beat variability of ARI (r</i> s</sub> = 0.74, p</i> = 0.008). There was a significant correlation between the beta-adrenergic blockade induced reduction in LF power of ARI and the witnessed reduction of beat-to-beat variability of ARI (r</i> s</sub> = 0.74, p</i> = 0.01). These clinical results accord with recent computational modeling studies which provide mechanistic insight into the interactions of LF oscillations and beat-to-beat variability of APD at the cellular level.</AbstractText>Beta-adrenergic blockade reduces LF oscillatory behavior of APD (ARI) in humans in vivo</i>. Our results support the importance of LF oscillations in modulating the response of BVR to beta-adrenergic blockers, suggesting that LF oscillations may play role in modulating beta-adrenergic mechanisms underlying BVR.</AbstractText>Copyright © 2020 Van Duijvenboden, Porter, Pueyo, Sampedro-Puente, Fernandez-Bes, Sidhu, Gould, Orini, Bishop, Hanson, Lambiase, Razavi, Rinaldi, Gill and Taggart.</CopyrightInformation> |
2,328,032 | A Large Solitary Hemangioblastoma of the Lateral Ventricles: A Case Report and Literature Review. | Hemangioblastoma (HB) in the supratentorial region of the brain is rare and only a few cases are reported on intraventricular HB. HB of the lateral ventricles is even rarer. We present a case of a 30-year-old man with generalized tonic clonic seizures. The brain computed tomography showed a 5.5 cm heterogeneous mass extending into both lateral ventricles with partial enhancement. Based on the size and imaging features, we present the fourth documented case of a large solitary intraventricular HB. Our approach to this unique case and some treatment complexities are also described. Considering the rarity of the case and the patient's imaging features, the present study provides a better understanding of HB and recommends HB to be considered in the differential diagnosis of masses in the lateral ventricles. In addition, some preventable pitfalls in the treatment of such complex cases are described. |
2,328,033 | Agenesis of the septum pellucidum: Prenatal diagnosis and outcome. | The purpose of this study is to describe the imaging findings in a group of fetuses with suspected agenesis of the septum pellucidum (ASP) and to evaluate their clinical outcome.</AbstractText>This is a retrospective multicenter study on a cohort of fetuses diagnosed with suspected ASP, between 2008 and 2017. The records of each patient, including ultrasound (US) and magnetic resonance studies, were reviewed and compared with the postnatal findings.</AbstractText>Forty-seven patients were included in the study at a mean gestational age of 26.6 weeks. In 17 patients, the ASP was considered isolated. Fourteen patients delivered live-born, and all 14 are developing normally. Three were lost to follow-up. Twenty-four patients had associated malformations involving the central nervous system (CNS); 13 were delivered (normal development [5], abnormal [6] and no follow-up [2]). Nine patients opted for termination, and two pregnancies were lost to follow-up. Six patients had non-CNS associated findings, two were delivered with normal neurological development and four had a termination.</AbstractText>Isolated ASP is usually associated with a favorable outcome; but in the presence of associated malformations, there is at least a 50% risk of abnormal development. Current imaging techniques can provide an accurate prognosis in cases when ASP appears isolated.</AbstractText>© 2020 John Wiley & Sons, Ltd.</CopyrightInformation> |
2,328,034 | Expression of Hey2 transcription factor in the early embryonic ventricles is controlled through a distal enhancer by Tbx20 and Gata transcription factors. | Development of multi-chambered heart is associated with spatio-temporal regulation of gene expression. A basic helix-loop-helix transcription factor Hey2 is specifically expressed in the embryonic mouse ventricles and is indispensable for ventricular myocyte differentiation, compartment identity and morphogenesis of the heart. However, how Hey2 transcription is precisely regulated in the heart remains unclear. In this study, we identified a distal Hey2 enhancer conserved in the mouse and human to possess specific transcriptional activity in ventricular free wall myocytes at the looping stage of cardiac development. Deletion of the enhancer significantly decreased endogenous Hey2 expression in the ventricular myocardium but not in other tissues of mouse embryos. Mutation/deletion of the conserved binding sites for T-box and Gata proteins, but not NK-2 proteins, abolished the enhancer activity, and Tbx20 null mice completely lost the enhancer activity in the embryonic ventricles. Luciferase reporter analysis suggested that the ventricular enhancer activity was controlled by Tbx20 through its DNA binding and cooperative function with cardiac Gata proteins. These results delineate a regulatory mechanism of ventricular Hey2 expression and help fully understand molecular cascades in myocardial cell differentiation and cardiac morphogenesis during embryonic development. |
2,328,035 | Thromboembolic Events Are Independently Associated with Liver Stiffness in Patients with Fontan Circulation.<ELocationID EIdType="pii" ValidYN="Y">418</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.3390/jcm9020418</ELocationID><Abstract><AbstractText><b>Background:</b> Thromboembolism (TE) and Fontan-associated liver disease (FALD) are common and lead to significant morbidity in Fontan circulations. Risk factors for TE and the potential link between TE and FALD are not well understood. The objective of this study was to evaluate the association between TE and the severity of FALD based on radiologic liver stiffness. <b>Methods:</b> Using a retrospective cohort study design, 85 Fontan patients (aged 27.7 ± 8.2 years) who had liver stiffness measurement were included. Multivariable logistic regression was used to determine independent associations with TE. <b>Results:</b> Sixteen patients (19%) had a history of TE after the Fontan procedure at a mean age of 21.4 ± 15.0 years. Patients with TE were significantly older at the time of the last evaluation (33.8 ± 11.7 vs. 26.3 ± 6.5 years, <i>p</i> = 0.03). Liver stiffness by MRI and ultrasound was higher in the TE group (5.1 ± 1.4 vs. 4.3 ± 1.2 kPa, <i>p</i> = 0.04 and 2.8 ± 0.4 vs. 2.4 ± 0.5 m/s, <i>p</i> = 0.04, respectively). On multivariable analysis, higher liver stiffness (odds ratio (OR): 2.12, <i>p</i> = 0.03) and older age (OR: 1.11, <i>p</i> = 0.03) were associated with TE. <b>Conclusions:</b> This study found an association between TE, age, and radiologic liver stiffness.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Alsaied</LastName><ForeName>Tarek</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Cincinnati Children's Hospital Heart Institute, Department of Pediatrics, University of Cincinnati College of Medicine Cincinnati, Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Possner</LastName><ForeName>Mathias</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Cincinnati Children's Hospital Heart Institute, Department of Pediatrics, University of Cincinnati College of Medicine Cincinnati, Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lubert</LastName><ForeName>Adam M</ForeName><Initials>AM</Initials><Identifier Source="ORCID">0000-0001-6401-9980</Identifier><AffiliationInfo><Affiliation>Cincinnati Children's Hospital Heart Institute, Department of Pediatrics, University of Cincinnati College of Medicine Cincinnati, Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Trout</LastName><ForeName>Andrew T</ForeName><Initials>AT</Initials><Identifier Source="ORCID">0000-0003-1431-4054</Identifier><AffiliationInfo><Affiliation>Department of Radiology, University of Cincinnati, College of Medicine Cincinnati, Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gandhi</LastName><ForeName>Janvi P</ForeName><Initials>JP</Initials><Identifier Source="ORCID">0000-0002-0868-8159</Identifier><AffiliationInfo><Affiliation>Summer Undergraduate Research Fellowship, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Garr</LastName><ForeName>BreAnn</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Division of Pharmacy, Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Palumbo</LastName><ForeName>Joseph S</ForeName><Initials>JS</Initials><AffiliationInfo><Affiliation>Cincinnati Children's Hospital Medical Center, Division of Hematology, Department of Pediatrics, University of Cincinnati College of Medicine Cincinnati, Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Palermo</LastName><ForeName>Joseph J</ForeName><Initials>JJ</Initials><AffiliationInfo><Affiliation>Cincinnati Children's Hospital Medical Center, Division of Gastroenterology, Department of Pediatrics, University of Cincinnati College of Medicine Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lorts</LastName><ForeName>Angela</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Cincinnati Children's Hospital Heart Institute, Department of Pediatrics, University of Cincinnati College of Medicine Cincinnati, Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Veldtman</LastName><ForeName>Gruschen R</ForeName><Initials>GR</Initials><AffiliationInfo><Affiliation>Adult Congenital Heart Disease, Cincinnati Children's Hospital and Heart Centre and King Faisal Specialist Hospital and Research Centre, Riyadh 45229, Saudi Arabia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Goldstein</LastName><ForeName>Stuart L</ForeName><Initials>SL</Initials><AffiliationInfo><Affiliation>Division of Nephrology, Cincinnati Children's Hospital Medical Centre, Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Opotowsky</LastName><ForeName>Alexander</ForeName><Initials>A</Initials><Identifier Source="ORCID">0000-0002-6107-2281</Identifier><AffiliationInfo><Affiliation>Cincinnati Children's Hospital Heart Institute, Department of Pediatrics, University of Cincinnati College of Medicine Cincinnati, Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dillman</LastName><ForeName>Johnathan R</ForeName><Initials>JR</Initials><AffiliationInfo><Affiliation>Department of Radiology, University of Cincinnati, College of Medicine Cincinnati, Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>02</Month><Day>04</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>J Clin Med</MedlineTA><NlmUniqueID>101606588</NlmUniqueID><ISSNLinking>2077-0383</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Fontan operation</Keyword><Keyword MajorTopicYN="N">anticoagulation</Keyword><Keyword MajorTopicYN="N">coagulation</Keyword><Keyword MajorTopicYN="N">liver stiffness</Keyword><Keyword MajorTopicYN="N">single ventricle congenital heart disease</Keyword><Keyword MajorTopicYN="N">thromboembolism</Keyword></KeywordList><CoiStatement>The authors declare no conflicts of interest. </CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>1</Month><Day>15</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>1</Month><Day>26</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>1</Month><Day>31</Day></PubMedPubDate><PubMedPubDate 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Nutr. 2017;64:3–7. doi: 10.1097/MPG.0000000000001382.</Citation><ArticleIdList><ArticleId IdType="doi">10.1097/MPG.0000000000001382</ArticleId><ArticleId IdType="pubmed">27540709</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">32032947</PMID><DateRevised><Year>2020</Year><Month>06</Month><Day>05</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1933-0693</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2020</Year><Month>Feb</Month><Day>07</Day></PubDate></JournalIssue><Title>Journal of neurosurgery</Title><ISOAbbreviation>J Neurosurg</ISOAbbreviation></Journal>Epidemiology, natural history, and optimal management of neurohypophyseal germ cell tumors. | <b>Background:</b> Thromboembolism (TE) and Fontan-associated liver disease (FALD) are common and lead to significant morbidity in Fontan circulations. Risk factors for TE and the potential link between TE and FALD are not well understood. The objective of this study was to evaluate the association between TE and the severity of FALD based on radiologic liver stiffness. <b>Methods:</b> Using a retrospective cohort study design, 85 Fontan patients (aged 27.7 ± 8.2 years) who had liver stiffness measurement were included. Multivariable logistic regression was used to determine independent associations with TE. <b>Results:</b> Sixteen patients (19%) had a history of TE after the Fontan procedure at a mean age of 21.4 ± 15.0 years. Patients with TE were significantly older at the time of the last evaluation (33.8 ± 11.7 vs. 26.3 ± 6.5 years, <i>p</i> = 0.03). Liver stiffness by MRI and ultrasound was higher in the TE group (5.1 ± 1.4 vs. 4.3 ± 1.2 kPa, <i>p</i> = 0.04 and 2.8 ± 0.4 vs. 2.4 ± 0.5 m/s, <i>p</i> = 0.04, respectively). On multivariable analysis, higher liver stiffness (odds ratio (OR): 2.12, <i>p</i> = 0.03) and older age (OR: 1.11, <i>p</i> = 0.03) were associated with TE. <b>Conclusions:</b> This study found an association between TE, age, and radiologic liver stiffness.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Alsaied</LastName><ForeName>Tarek</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Cincinnati Children's Hospital Heart Institute, Department of Pediatrics, University of Cincinnati College of Medicine Cincinnati, Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Possner</LastName><ForeName>Mathias</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Cincinnati Children's Hospital Heart Institute, Department of Pediatrics, University of Cincinnati College of Medicine Cincinnati, Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lubert</LastName><ForeName>Adam M</ForeName><Initials>AM</Initials><Identifier Source="ORCID">0000-0001-6401-9980</Identifier><AffiliationInfo><Affiliation>Cincinnati Children's Hospital Heart Institute, Department of Pediatrics, University of Cincinnati College of Medicine Cincinnati, Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Trout</LastName><ForeName>Andrew T</ForeName><Initials>AT</Initials><Identifier Source="ORCID">0000-0003-1431-4054</Identifier><AffiliationInfo><Affiliation>Department of Radiology, University of Cincinnati, College of Medicine Cincinnati, Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gandhi</LastName><ForeName>Janvi P</ForeName><Initials>JP</Initials><Identifier Source="ORCID">0000-0002-0868-8159</Identifier><AffiliationInfo><Affiliation>Summer Undergraduate Research Fellowship, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Garr</LastName><ForeName>BreAnn</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Division of Pharmacy, Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Palumbo</LastName><ForeName>Joseph S</ForeName><Initials>JS</Initials><AffiliationInfo><Affiliation>Cincinnati Children's Hospital Medical Center, Division of Hematology, Department of Pediatrics, University of Cincinnati College of Medicine Cincinnati, Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Palermo</LastName><ForeName>Joseph J</ForeName><Initials>JJ</Initials><AffiliationInfo><Affiliation>Cincinnati Children's Hospital Medical Center, Division of Gastroenterology, Department of Pediatrics, University of Cincinnati College of Medicine Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lorts</LastName><ForeName>Angela</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Cincinnati Children's Hospital Heart Institute, Department of Pediatrics, University of Cincinnati College of Medicine Cincinnati, Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Veldtman</LastName><ForeName>Gruschen R</ForeName><Initials>GR</Initials><AffiliationInfo><Affiliation>Adult Congenital Heart Disease, Cincinnati Children's Hospital and Heart Centre and King Faisal Specialist Hospital and Research Centre, Riyadh 45229, Saudi Arabia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Goldstein</LastName><ForeName>Stuart L</ForeName><Initials>SL</Initials><AffiliationInfo><Affiliation>Division of Nephrology, Cincinnati Children's Hospital Medical Centre, Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Opotowsky</LastName><ForeName>Alexander</ForeName><Initials>A</Initials><Identifier Source="ORCID">0000-0002-6107-2281</Identifier><AffiliationInfo><Affiliation>Cincinnati Children's Hospital Heart Institute, Department of Pediatrics, University of Cincinnati College of Medicine Cincinnati, Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dillman</LastName><ForeName>Johnathan R</ForeName><Initials>JR</Initials><AffiliationInfo><Affiliation>Department of Radiology, University of Cincinnati, College of Medicine Cincinnati, Cincinnati, OH 45229, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>02</Month><Day>04</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>J Clin Med</MedlineTA><NlmUniqueID>101606588</NlmUniqueID><ISSNLinking>2077-0383</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Fontan operation</Keyword><Keyword MajorTopicYN="N">anticoagulation</Keyword><Keyword MajorTopicYN="N">coagulation</Keyword><Keyword MajorTopicYN="N">liver stiffness</Keyword><Keyword MajorTopicYN="N">single ventricle congenital heart disease</Keyword><Keyword MajorTopicYN="N">thromboembolism</Keyword></KeywordList><CoiStatement>The authors declare no conflicts of interest. </CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>1</Month><Day>15</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>1</Month><Day>26</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>1</Month><Day>31</Day></PubMedPubDate><PubMedPubDate 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Nutr. 2017;64:3–7. doi: 10.1097/MPG.0000000000001382.</Citation><ArticleIdList><ArticleId IdType="doi">10.1097/MPG.0000000000001382</ArticleId><ArticleId IdType="pubmed">27540709</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">32032947</PMID><DateRevised><Year>2020</Year><Month>06</Month><Day>05</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1933-0693</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2020</Year><Month>Feb</Month><Day>07</Day></PubDate></JournalIssue><Title>Journal of neurosurgery</Title><ISOAbbreviation>J Neurosurg</ISOAbbreviation></Journal><ArticleTitle>Epidemiology, natural history, and optimal management of neurohypophyseal germ cell tumors.</ArticleTitle><Pagination><StartPage>1</StartPage><EndPage>9</EndPage><MedlinePgn>1-9</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.3171/2019.10.JNS191136</ELocationID><ELocationID EIdType="pii" ValidYN="Y">2019.10.JNS191136</ELocationID><Abstract><AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">Intracranial germ cell tumors (iGCTs) often arise at the neurohypophysis, their second most common origination, following the pineal region. Neurohypophyseal iGCTs present with stereotypical symptoms, including pituitary dysfunction and visual field deficit, due to their suprasellar location. The goal of this study was to present a large, longitudinal single-institution experience with neurohypophyseal iGCTs to better understand their natural history and identify opportunities for further improvement in treatment outcomes.<AbstractText Label="METHODS" NlmCategory="METHODS">This is a retrospective, single-institution cohort study of neurohypophyseal iGCTs treated between 1988 and 2017, with a focus on the epidemiology, presentation, natural history, and treatment.<AbstractText Label="RESULTS" NlmCategory="RESULTS">Thirty-five neurosurgically managed patients met inclusion criteria; the median age was 18 years (3 months to 49 years), and 74% of patients were male (n = 26). Thirty-one tumors were germinomas, and 4 were nongerminomatous iGCTs. Presenting symptoms included pituitary insufficiency in 76% (n = 25), visual deficit in 45% (n = 15), and diabetes insipidus (DI) in 61% (n = 20) of patients. Index symptoms included isolated DI in 10 (36%), isolated hormone deficiency in 14 (50%), and concomitant DI and hormone deficiency symptoms in 4 (14%). Radiographic diagnostic latency was common, occurring at a median of 363 days (range 9-2626 days) after onset of the first symptoms and was significantly associated with both DI and hormone deficiency as the index symptoms (no DI vs DI: 360 vs 1083 days, p = 0.009; no hormone deficiency vs hormone deficiency: 245 vs 953 days, p = 0.004). Biochemical abnormalities were heterogeneous; each pituitary axis was dysfunctional in at least 1 patient, with most patients demonstrating at least 2 abnormalities, and pretreatment dysfunction demonstrating a nonsignificant trend toward association with long-term posttreatment hormone supplementation. Among germinomas, whole-brain or whole-ventricle radiotherapy demonstrated significantly improved progression-free and overall survival compared with local therapy (p = 0.009 and p = 0.004, respectively).<AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Neurohypophyseal iGCTs are insidious tumors that may pose a diagnostic dilemma, as evidenced by the prolonged latency before radiographic confirmation. Serial imaging and close endocrine follow-up are recommended in patients with a characteristic clinical syndrome and negative imaging, due to the propensity for radiographic latency. Pretreatment biochemical abnormalities may indicate higher risk of posttreatment pituitary insufficiency, and all patients should receive careful endocrine follow-up. Local radiotherapy is prone to treatment failure, while whole-ventricle treatment is associated with improved survival in germinomas. |
2,328,036 | Test-retest reliability and sample size estimates after MRI scanner relocation. | Many factors can contribute to the reliability and robustness of MRI-derived metrics. In this study, we assessed the reliability and reproducibility of three MRI modalities after an MRI scanner was relocated to a new hospital facility.</AbstractText>Twenty healthy volunteers (12 females, mean age (standard deviation) ​= ​41 (11) years, age range [25-66]) completed three MRI sessions. The first session (S1) was one week prior to the 3T GE HDxt scanner relocation. The second (S2) occurred nine weeks after S1 and at the new location; a third session (S3) was acquired 4 weeks after S2. At each session, we acquired structural T1-weighted, pseudo-continuous arterial spin labelled, and diffusion tensor imaging sequences. We used longitudinal processing streams to create 12 summary MRI metrics, including total gray matter (GM), cortical GM, subcortical GM, white matter (WM), and lateral ventricle volume; mean cortical thickness; total surface area; average gray matter perfusion, and average diffusion tensor metrics along principal white matter pathways. We compared mean MRI values and variance at the old scanner location to multiple sessions at the new location using Bayesian multi-level regression models. K-fold cross validation allowed identification of important predictors. Whole-brain analyses were used to investigate any regional differences. Furthermore, we calculated within-subject coefficient of variation (wsCV), intraclass correlation coefficient (ICC), and dice similarity index (SI) of cortical segmentations across scanner relocation and within-site. Additionally, we estimated sample sizes required to robustly detect a 4% difference between two groups across MRI metrics.</AbstractText>All global MRI metrics exhibited little mean difference and small variability (bar cortical gray matter perfusion) both across scanner relocation and within-site repeat. T1- and DTI-derived tissue metrics showed ​< ​|0.3|% mean difference and <1.2% variance across scanner location and <|0.4|% mean difference and <0.8% variance within the new location, with between-site intraclass correlation coefficient (ICC) ​> ​0.80 and within-subject coefficient of variation (wsCV) ​< ​1.4%. Mean cortical gray matter perfusion had the highest between-session variability (6.7% [0.3, 16.7], estimate [95% uncertainty interval]), and hence the smallest ICC (0.71 [0.44,0.92]) and largest wsCV (13.4% [5.4, 18.1]). No global metric exhibited evidence of a meaningful mean difference between scanner locations. However, surface area showed evidence of a mean difference within-site repeat (between S2 and S3). Whole-brain analyses revealed no significant areas of difference between scanner relocation or within-site. For all metrics, we found no support for a systematic difference in variance across relocation sites compared to within-site test-retest reliability. Necessary sample sizes to detect a 4% difference between two independent groups varied from a maximum of n ​= ​362 per group (cortical gray matter perfusion), to total gray matter volume (n ​= ​114), average fractional anisotropy (n ​= ​23), total gray matter volume normalized by intracranial volume (n ​= ​19), and axial diffusivity (n ​= ​3 per group).</AbstractText>Cortical gray matter perfusion was the most variable metric investigated (necessitating large sample sizes to identify group differences), with other metrics showing substantially less variability. Scanner relocation appeared to have a negligible effect on variability of the global MRI metrics tested. This manuscript reports within-site test-retest variability to act as a tool for calculating sample size in future investigations. Our results suggest that when all other parameters are held constant (e.g., sequence parameters and MRI processing), the effect of scanner relocation is indistinguishable from within-site variability, but may need to be considered depending on the question being investigated.</AbstractText>Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,037 | MicroRNA-193b-3p alleviates focal cerebral ischemia and reperfusion-induced injury in rats by inhibiting 5-lipoxygenase expression. | Ischemic stroke has become one of the main causes of death worldwide. MicroRNAs (miRNAs) have been implicated in cerebral ischemia-reperfusion (I/R) injury and could serve as therapeutic targets. 5-Lipoxygenase (5-LOX) is a key enzyme in the biosynthesis of leukotrienes and has been implicated in inflammatory central nerve system disorders. The objective of this study was to explore the neuroprotective effects of miR-193b-3p against focal cerebral I/R injury in rats by regulating 5-LOX expression.</AbstractText>Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion and reperfusion injury. The level of miR-193b-3p expression was observed in the rat cortical peri-infarct region after focal cerebral I/R injury. Bioinformatics analysis was used to predict the binding sites of miR-193b-3p, and a dual-luciferase reporter gene assay was applied to verify the potential interaction between 5-LOX mRNA and miR-193b-3p. Then, rats were injected with a miR-193b-3p agomir (modified and enhanced mimic) or antagomir (modified and enhanced inhibitor) in the right lateral ventricle of the brain. Neurological deficit scores, infarct volumes, neuron damage and 5-LOX enzymatic activity and expression were measured. In an in vitro experiment, cultured PC12 cells were exposed to oxygen-glucose deprivation and reperfusion (OGD/R). OGD/R-induced cells were treated with a miR-193b-3p mimic or inhibitor and 5-LOX siRNA. Cell viability, lactate dehydrogenase release, apoptosis rate and 5-LOX expression were evaluated.</AbstractText>The level of miR-193b-3p expression was increased in the cortical peri-infarct region of rats with cerebral focal I/R injury. The results of the dual-luciferase reporter gene assay showed that a miR-193b-3p binding site was located in the 3' untranslated region (3'UTR) of 5-LOX mRNA. Neurological deficit scores, infarct volumes and neuronal injury were alleviated by miR-193b-3p agomir treatment but aggravated by miR-193b-3p antagomir. Furthermore, leukotriene B4, cysteinyl-leukotrienes and 5-LOX expression in the cortical peri-infarct region of rats with focal cerebral I/R injury were also downregulated by miR-193b-3p agomir treatment but upregulated by miR-193b-3p antagomir. In PC12 cells, miR-193b-3p mimic significantly decreased OGD/R-induced cell death and reduced lactate dehydrogenase release and 5-LOX expression. In contrast, miR-193b-3p inhibitor exacerbated OGD/R-induced injury in PC12 cells. Additionally, the in vitro effects of miR-193b-3p inhibitor on OGD/R-induced cell injury were partially reversed by 5-LOX siRNA treatment.</AbstractText>MiR-193b-3p has a potentially neuroprotective effect on focal cerebral I/R-induced injury by inhibiting 5-LOX expression.</AbstractText>Copyright © 2020 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,038 | Widely Distributed Neurotensinergic Neurons in the Brainstem Regulate NREM Sleep in Mice. | Classical transection studies suggest that, in addition to the hypothalamus, the brainstem is essential for non-rapid eye movement (NREM) sleep. The circuits underlying this function, however, have remained largely unknown. We identified a circuit distributed in the midbrain, pons, and medulla that promotes NREM sleep in mice. We focused on the sublaterodorsal tegmentum, an area implicated in dual regulation of REM and NREM sleep. Transcriptomic and genetic analyses revealed that neurons positive for the neuropeptide neurotensin promote NREM sleep. Further analyses identified downstream NREM sleep-promoting neurons in the dorsal deep mesencephalic nucleus, the lateral part of the periaqueductal gray, and the medial vestibular nucleus that were also neurotensinergic. Infusion of neurotensin into the fourth ventricle induced NREM sleep-like cortical activity, whereas mice deficient for neurotensin exhibited increased REM sleep, implicating the involvement of the neuropeptide itself. These findings identify a widely distributed NREM sleep-regulating circuit in the brainstem with a common molecular property. |
2,328,039 | [Application of a modified Time-SLIP MRI sequence for visualization of cerebrospinal fluid movement in the cerebral aqueduct and cervical spinal canal]. | Прямая визуализация быстрых перемещений ликвора - актуальная задача нейрохирургии, имеющая такие приложения, как оценка наличия и степени тяжести гидроцефалии, эффективности вентрикулостомии III желудочка. Цель исследования - оценить возможности модифицированной импульсной МРТ последовательности Time-SLIP для визуализации движения жидкости (ликвора) в водопроводе мозга и шейном отделе позвоночного канала с помощью регистрации перемещения ликвора (LOM) на фантоме, у здоровых и больных людей. Материал и методы. Исследования проводились на фантоме, имитирующем пульсовые движения ликвора, у здоровых добровольцев (9 человек) и у 12 пациентов без нарушений ликвородинамики со средними показателями ликворотока, а также у 1 больного после вентрикулостомии III желудочка. Использовали магнитно-резонансный (МР) томограф 1,5 Тл. Параметры Time-SLIP: TR 8500 мс; TEeff 80 мс; Thk 5,0 мм; ширина tag-зоны 30 мм; NEX 7; время инверсии (BBTI) 2000/3000 мс, без кардиосинхронизации. Время сканирования 2:16 мин. Оцениваемый параметр - длина перемещения ликвора (Length Of Motion, LOM). Результаты. По данным исследований на фантоме, моделирующем различные условия колебательных движений жидкости, средняя ошибка определения LOM для модифицированного режима Time-SLIP составила 20%. С помощью данной методики для водопровода мозга получены следующие данные LOM (медиана, 25-75-процентный квартили): для BBTI 2000 мс - 13 мм (9,5-16,0 мм), для BBTI 3000 мс - 30,2 мм (23,7-35,3 мм), т.е. в 2,3 раза больше. Эта разница может быть объяснена интенсивным турбулентным током, приводящим к быстрому обмену ликвором между III и IV желудочками головного мозга и протяженным распространением ликвора в течение несколько сердечных сокращений. Определены количественные показатели перемещения ликвора на уровне C<sub>I</sub>-С<sub>II</sub>. Дополнительно показано применение Time-SLIP для оценки состоятельности фистулы III желудочка. Выводы. Предложена модифицированная импульсная последовательность Time-SLIP, не требующая кардиосинхронизации. Средняя относительная ошибка определения длины перемещения ликвора - 20%. Получены средние количественные показатели перемещения ликвора в водопроводе мозга и на уровне C<sub>I</sub>-С<sub>II</sub>. Для водопровода мозга показан турбулентный ток ликвора, приводящий к быстрому обмену между III и IV желудочками. |
2,328,040 | [Central neurocytomas: surgical treatment outcomes and new trends and approaches in the treatment]. | Центральные нейроцитомы головного мозга относятся к редко встречающимся доброкачественным опухолям боковых желудочков головного мозга. Основным методом их лечения является хирургическая резекция. Удаление позволяет добиться длительного безрецидивного периода, однако хирургическое вмешательство сопряжено с рядом значительных трудностей, что определяется локализацией, размерами и особенностями кровоснабжения этих опухолей. Послеоперационный период часто осложняется развитием геморрагических осложнений, нарушением ликвороциркуляции и нарастанием неврологической симптоматики. Цель исследования - оценка эффективности хирургического лечения пациентов с нейроцитомами головного мозга; оценка риска развития осложнений после удаления нейроцитом головного мозга и разработка методов их профилактики. Материал и методы. В работе представлены результаты хирургического лечения 115 пациентов с центральными нейроцитомами головного мозга в период с 2008 по 2017 г. Детально описаны выбор хирургического доступа, особенности операций, проведена оценка радикальности с учетом локализации и размеров опухолей. Оценены ближайшие клинические результаты лечения, проанализированы осложнения и показаны методы их профилактики и лечения. Результаты. Анализ данных показал, что радикальное удаление выполнено у 41 (36%) пациента, субтотальная резекция - у 37 (32%) и частичное удаление - у 37 (32%). Самыми частыми и опасными осложнениями были нарушение ликвородинамики по окклюзионному типу с развитием гидроцефалии у 23 (20%) пациентов, кровоизлияния в остатки опухоли, в большинстве случаев явившиеся показанием к немедленной ревизии операционной раны, у 25 (22%) пациентов. После удаления опухоли в раннем послеоперационном периоде практически у всех больных наблюдалось ухудшение состояния с преходящим нарастанием общемозговой и очаговой симптоматики. Степень и продолжительность этого нарастания различались. В 50% случаев послеоперационное состояние характеризовалось снижением произвольной активности, сонливостью либо тревожным состоянием, двигательным или речевым беспокойством. Выводы. Мы предлагаем рассматривать удаление нейроцитом головного мозга как основной метод лечения, несмотря на возможные осложнения и последствия операции. |
2,328,041 | Regulation of muscle and metabolic physiology by hypothalamic erythropoietin independently of its peripheral action. | The glycoprotein hormone erythropoietin (EPO) is required for erythropoiesis, and the kidney is the primary site of adult EPO synthesis. Limited evidence has suggested that EPO could be detectable in the brain under certain conditions, but it remains unknown if the brain might have its own EPO system for biological functions that are independent of peripheral EPO production and action. We performed this study to address this question using mice under normal conditions versus pathophysiological conditions including aging and dietary obesity.</AbstractText>EPO expression was measured in different brain regions as well as in the cerebrospinal fluid. Hypothalamic ventricular EPO was administered to physiologically examine possible therapeutic effects on the conditions of aging and dietary obesity. Body weight, body composition, insulin tolerance, and glucose tolerance were measured to assess the central effects of EPO on metabolic physiology, and muscle strength and histology were analyzed to assess the central effects of EPO on muscle function. In addition, β2-adrenergic receptor knockout bone marrow transplant was employed to determine the potential role of bone marrow in linking the brain to some of these peripheral functions.</AbstractText>This study revealed that EPO is expressed in the ventromedial hypothalamus in addition to a few other brain regions and is present in the cerebrospinal fluid. Unlike blood EPO concentration, which increased with aging and dietary obesity, hypothalamic EPO decreased in these disease conditions. Therapeutically, aged mice were chronically treated with EPO in the hypothalamic ventricle, showing an increase in lean mass, while body weight and fat mass decreased as a result of a moderate reduction of food intake. Both muscle and metabolic functions were improved by this central treatment, and mechanistically, adrenergic signals to the bone marrow played a role in conveying hypothalamic EPO to these peripheral actions. Dietary obesity was also studied, showing that hypothalamic EPO treatment caused a reduction in food intake and obesity, leading to improved metabolic functions related to decreased fat as well as increased lean mass.</AbstractText>Hypothalamic EPO plays a role in the central regulation of muscle and metabolic physiology, while its decline contributes to aging and obesity physiology in a manner that is independent of peripheral EPO.</AbstractText>Copyright © 2019 The Author(s). Published by Elsevier GmbH.. All rights reserved.</CopyrightInformation> |
2,328,042 | Maternal periconceptional and first trimester protein restriction in beef heifers: effects on placental parameters and fetal and neonatal calf development. | Few studies have investigated the effects of nutrition during the periconception and early gestation periods on fetal and placental development in cattle. In this study, nulliparous yearling heifers (n=360) were individually fed a diet high or low in protein (HPeri and LPeri) beginning 60 days before conception. From 24 to 98 days after conception, half of each treatment group was changed to the alternative high- or low-protein diet (HPost and LPost) yielding four groups in a 2×2 factorial design. A subset of heifers (n=46) was necropsied at 98 days after conception and fetoplacental development assessed. Placentome number and volume decreased in response to LPeri and LPost diets respectively. Absolute lung, pancreas, septum and ventricle weights decreased in LPost versus HPost fetuses, whereas the post-conception diet altered absolute and relative liver and brain weights depending on sex. Similarly, changes in fetal hepatic gene expression of factors regulating growth, glucose output and lipid metabolism were induced by protein restriction in a sex-specific manner. At term, neonatal calf and placental measures were not different. Protein restriction of heifers during the periconception and early gestation periods alters fetoplacental development and hepatic gene expression. These changes may contribute to functional consequences for progeny, but this may not be apparent from gross morphometry at birth. |
2,328,043 | Lack of Thy1 defines a pathogenic fraction of cardiac fibroblasts in heart failure. | In response to heart injury, inflammation, or mechanical overload, quiescent cardiac fibroblasts (CFs) can become activated myofibroblasts leading to pathological matrix remodeling and decline in cardiac function. Specific targeting of fibroblasts may thus enable new therapeutic strategies to delay or reverse the progression of heart failure and cardiac fibrosis. However, it remains unknown if all CFs are equally responsive to specific pathological insults and if there exist sub-populations of resident fibroblasts in the heart that have distinctive pathogenic phenotypes. Here, we show that in response to transverse aortic constriction (TAC)-induced heart failure, previously uncharacterized Thy1<sup>neg</sup> (Thy1-/MEFSK4+/CD45-/CD31-) fraction of mouse ventricular fibroblasts became more abundant and attained a more activated, pro-fibrotic myofibroblast phenotype compared to Thy1<sup>Pos</sup> fraction. In a tissue-engineered 3D co-culture model of healthy cardiomyocytes and freshly isolated CFs, Thy1<sup>neg</sup> CFs from TAC hearts significantly decreased cardiomyocyte contractile function and calcium transient amplitude, and increased extracellular collagen deposition yielding a profibrotic heart tissue phenotype. In vivo, mice with global knockout of Thy1 developed more severe cardiac dysfunction and fibrosis in response to TAC-induced heart failure than wild-type mice. Taken together, our studies identify cardiac myofibroblasts lacking Thy1 as a pathogenic CF fraction in cardiac fibrosis and suggest important roles of Thy1 in pathophysiology of heart failure. |
2,328,044 | Presentation, Surgical Management, and Postoperative Outcome of a Fourth Ventricular Cavernous Malformation: Case Report and Review of Literature. | Brainstem cavernous malformations (CMs) represent dangerous clinical entities associated with high rates of rebleeding and morbidity compared with those in other locations. Particularly rare are those located within the fourth ventricle. Although fourth ventricular CMs are favorable from a surgical standpoint, there are no defined guidelines on definitive indications and optimal timing of surgery. In addition, the surgical approaches, anatomic considerations, and general observations regarding these lesions are not well reported in the literature.</AbstractText>A 27-year-old man with a known history of a CM on the floor of the fourth ventricle presented with new cranial nerve deficits and signs of increased intracranial pressure. Imaging revealed acute bleeding from a fourth ventricular CM. The patient was urgently taken to surgery for resection. Despite a noneventful surgery which resulted in gross total resection, the patient developed a unique constellation of cranial nerve deficits postoperatively, most notably of which was eight-and-a-half syndrome.</AbstractText>CMs of the fourth ventricle are rare clinical entities that can be treated successfully with surgery. The indications for surgery may not always be clear-cut; therefore, the neurosurgeon's decision to proceed with surgery must reside on a case-by-case basis using a multifactorial approach. The location of these lesions presents unique challenges given their proximity to vital structures and the technical difficulty required. For these reasons, the resection of these lesions often results in new or persistent neurologic deficits. However, despite the associated risks, the potential benefits of surgery oftentimes outweigh the risks of the alternative.</AbstractText>Copyright © 2020 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,045 | Schisandrin A and B enhance the dentate gyrus neurogenesis in mouse hippocampus. | Schisandrin A and B (Sch A and B) are the main effective components of Schisandra chinensis (S. chinensis), which is traditionally used to enhance mental and intellectual functions in eastern Asia. Previously, we reported Sch A and B remarkably affect adult neurogenesis in the subventricular zone of mouse lateral ventricle. Since the neurogenesis in the hippocampal dentate gyrus (DG) is more important to learning, memory and cognition, here we further examined their effects on the adult DG neurogenesis. Phosphohistone H3 (PHH3) immunostaining showed that Sch B significantly enhanced the cell proliferation in the DG. Glial fibrillary acidic protein (GFAP, mostly labels astrocytes and some stem cells) staining was used to further identify the proliferating cell type. Dramatically, increases of GFAP<sup>+</sup> cells in both Sch A and B treated groups were observed. What's more, the total numbers of the mature neurons labeled by neuron-specific nuclear protein (NeuN) were also increased in both Sch A and B treated groups compared with the controls. Together, Sch A and B enhance the adult DG neurogenesis by increasing astrocytes/stem cells and improving the survival and maturation of DG neurons. Our study shed a new light on the neuropharmacological functions of the herbal medicine S. chinensis. |
2,328,046 | Medical management of acute loss of vision in tuberculous meningitis: A case report. | Blindness and vision impairment are unpredictable complications of tuberculous meningitis (TBM) that are often unrecognized in the acute stages of illness due to inability to assess vision in patients with depressed levels of consciousness or confusion. We present a patient with definite TBM confirmed by positive Xpert MTB/RIF assay of cerebrospinal fluid (CSF) who developed binocular blindness two weeks after diagnosis and initiation of standard anti-tuberculosis treatment (ATT). Ophthalmological exam demonstrated complete bilateral abducens nerve palsies, impaired pupillary responses to light, normal optic discs, and visual acuity of hand motion only in each eye. Brain CT showed progressive enlargement of the third and lateral ventricles. We managed the patient medically with dexamethasone, acetazolamide, and substitution of moxifloxacin for ethambutol. Serial brain CTs confirmed gradual resolution of hydrocephalus. The patient had complete neurological recovery at six months except for residual blindness in the right eye. Visual acuity in the left eye recovered to normal (20/20). The assessment and management of vision impairment in TBM is discussed. |
2,328,047 | Presumed cholesterinic granulomas detected on CT in horses are associated with increased lateral ventricle height and age. | Cholesterinic granulomas are mass-like lesions that form at the choroid plexus of the ventricular system. Large cholesterinic granulomas within the lateral ventricles have been reported to cause severe neurological signs. However, little data are available about their prevalence or appearance in the overall population. The objective was to report the prevalence of presumed cholesterinic granulomas on CT in a population of horses, and investigate associations between presumed cholesterinic granuloma presence, lateral ventricle size, age, and neurological signs. The study was cross sectional, CT scans of the head were assessed for presumed cholesterinic granuloma presence and size, and lateral ventricle height. Computed tomography findings and clinical information were compared using nonparametric testing. Computed tomography scans of 139 horses were included. Presumed cholesterinic granulomas were found in 22 horses (15.8%), nine were unilateral and 13 bilateral. A significant increase in prevalence was observed with age (P < .0001), with 38% of horses over 15 years old affected. The median volume of presumed cholesterinic granulomas was 242 mm<sup>3</sup> with a range from 51 to 2420 mm<sup>3</sup> . The mean lateral ventricle height was significantly increased in horses with presumed cholesterinic granulomas present (P = .004), with a median of 7.3 mm compared to 4.9 mm without. Neurological signs were not associated with presumed cholesterinic granuloma presence or lateral ventricle height. Fourth ventricle mineralizations were found in seven horses, which may represent cholesterinic granulomas. In conclusion, presumed cholesterinic granulomas occurred in a large proportion of the examined population and are associated with increased lateral ventricle dilation and advanced age. |
2,328,048 | Changes in Callosal Angle After Successful Endoscopic Third Ventriculostomy Procedure in Pediatric Patients. | To determine whether callosal angle (CA) measurement, a diagnostic and prognostic tool used for normal-pressure hydrocephalus in adults, is a reliable radiological parameter for evaluating endoscopic third ventriculostomy (ETV) outcomes in pediatric patients.</AbstractText>Forty-seven pediatric patients with hydrocephalus who underwent successful ETV in our clinic between 2011 and 2015 were included in this study. Preoperative and postoperative three-month CA, lateral ventricle frontal horn (LVFH) width, Evans' index (EI), and frontal-occipital horn ratio (FOR) parameters were recorded, with changes analyzed using a paired-samples t-test.</AbstractText>There were 29 male and 18 female patients included within the cohort. For mean preoperative values, LVFH width was 58.8 ± 14.9 mm, EI was 0.43 ± 0.09, FOR was 0.51 ± 0.74, and CA was 78.5° ± 36.4°. Separately, for mean postoperative values, LVFH width was 54 ± 14.2 mm, EI was 0.39 ± 0.09, FOR was 0.47 ± 0.07, and CA was 104.5° ± 32.6°. The CA was increased and the LVFH width, EI, and FOR were decreased in all patients within three months after surgery. The postoperative three-month change in CA was higher than those observed in the other parameters.</AbstractText>Changes in CA after successful ETV were dramatically higher than those in the other ventricular parameters. For this reason, we suggest CA be used as a radiological criterion during early radiological follow-up of patients after ETV.</AbstractText> |
2,328,049 | Relationships between recurrence patterns and subventricular zone involvement or CD133 expression in glioblastoma. | We previously reported that CD133 expression correlated with the recurrence pattern of glioblastoma (GBM). Subventricular zone (SVZ) involvement may also be associated with distant recurrence in GBM. Therefore, we herein investigated whether the combined analysis of SVZ involvement and CD133 expression is useful for predicting the pattern of GBM recurrence.</AbstractText>We retrospectively analyzed 167 cases of GBM. Tumors were divided into four groups based on spatial relationships between contrast-enhanced lesions (CEL) and the SVZ or cortex (Ctx) on MRI. The initial recurrence pattern (local/distant) was obtained from medical records. To identify factors predictive of recurrence, we examined CD133 expression by immunohistochemical, clinical (age, sex, KPS, Ki-67 labeling index, surgery, and MRI characteristics), and genetic (IDH1, MGMT, and BRAF) factors.</AbstractText>The CD133 expression rate was higher in SVZ-positive tumors than in SVZ-negative tumors (P = 0.046). Distant recurrence was observed in 21% of patients, and no significant difference was noted in recurrence patterns among the four groups. However, strong CD133 expression was associated with a shorter time to distant recurrence in univariate, multivariate, and propensity-matched scoring analyses (P < 0.0001, P = 0.001, and P = 0.0084, respectively). In the combined analysis, distant recurrence was the most frequent (70%) in group III (SVZ-negative, Ctx-positive) GBM and those with high CD133 expression rates (≥ 15%).</AbstractText>An integrated analysis of CD133 expression and MRI-based tumor classification may be useful for predicting the recurrence pattern of GBM.</AbstractText> |
2,328,050 | Accuracy and complication rates of external ventricular drain placement with twist drill and bolt system versus standard trephine and tunnelation: a retrospective population-based study. | An external ventricular drain (EVD) is typically indicated in the presence of hydrocephalus and increased intracranial pressure (ICP). Procedural challenges have prompted the development of different methods to improve accuracy, safety, and logistics.</AbstractText>EVD placement and complications rates were compared using two surgical techniques; the standard method (using a 14-mm trephine burrhole with the EVD tunnelated through the skin) was compared to a less invasive method (EVD placed through a 2.7-3.3-mm twist drill burrhole and fixed to the bone with a bolt system).</AbstractText>Retrospective observational study in a single-centre setting between 2008 and 2018. EVD placement was assessed using the Kakarla scoring system. We registered postoperative complications, surgery duration and number of attempts to place the EVD.</AbstractText>Two hundred seventy-two patients received an EVD (61 bolt EVDs, 211 standard EVDs) in the study period. Significant differences between the bolt system and the standard method were observed in terms of revision surgeries (8.2% vs. 21.5%, p = 0.020), surgery duration (mean 16.5 vs. 28.8 min, 95% CI 7.64, 16.8, p < 0.001) and number of attempts to successfully place the first EVD (mean 1.72 ± 1.2 vs. 1.32 ± 0.8, p = 0.017). There were no differences in accuracy of placement or complication rates.</AbstractText>The two methods show similar accuracy and postoperative complication rates. Observed differences in both need for revisions and surgery duration favoured the bolt group. Slightly, more attempts were needed to place the initial EVD in the bolt group, perhaps reflecting lower flexibility for angle correction with a twist drill approach.</AbstractText> |
2,328,051 | Management of paediatric hydrocephalous with Miethke fixed pressure gravitational valves. The Alder Hey Children's Hospital experience. | The management of paediatric hydrocephalous remains challenging with the complication and revision rates being consistent in the literature. We hypothesise that the use of a fixed pressure gravitational valve for all de novo shunt insertions decreases the rate of functional revisions and that by implementing the routine use of gravitational valves in children, we would see a reduction in over-drainage and slit ventricle syndrome.</AbstractText>Retrospective data collection in a single centre, between February 2010 and August 2018. All patients undergoing fixed pressure gravitational Miethke valve insertion were included. We collected data on patients' demographics, reason for shunt insertion, type of valve and time to and reason for first revision. Data analysis was done with SPSS.</AbstractText>A total of 235 patients were included in our study (124 males, 111 females), aged from 0 to 18.6 years (median 0.28). A total of 99 shunt revisions were documented, 30 of which secondary to ventricular catheter malfunction and 28 secondary to infection. The overall mechanical valve survival rates were 88.5%, 86.4% and 85.5% at 1, 2 and 5 years, respectively. Shunt revision due to over-drainage was documented in only 3 cases (1.3%).</AbstractText>Our results are in agreement with existing literature regarding shunt failures secondary to all extrinsic factors to the valve (infection and mechanical failure). We have shown that the use of a Miethke fixed pressure valve for all de novo shunt insertions in paediatric hydrocephalus decreases the need for functional revisions with valve survival rates being superior to the ones described for other types.</AbstractText> |
2,328,052 | Encephalitis with radial perivascular emphasis: Not necessarily associated with GFAP antibodies. | Autoimmune steroid-responsive meningoencephalomyelitis with linear perivascular gadolinium enhancement in brain MRI is regarded as glial fibrillary acidic protein (GFAP) astrocytopathy characterized by anti-GFAP antibodies (ABs). We questioned whether anti-GFAP ABs are necessarily associated with this syndrome.</AbstractText>Two patients with a strikingly similar disease course suggestive of autoimmune GFAP astrocytopathy are reported. Clinical examination, MRI, laboratory, and CSF analysis were performed. Neuropathologic examination of brain tissue was obtained from one patient. Serum and CSF were additionally tested using mouse brain slices, microglia-astrocyte cocultures, and a GFAP-specific cell-based assay.</AbstractText>Both patients presented with subacute influenza-like symptoms and developed severe neurocognitive and neurologic deficits and impaired consciousness. MRIs of both patients revealed radial perivascular gadolinium enhancement extending from the lateral ventricles to the white matter suggestive of autoimmune GFAP astrocytopathy. Both patients responded well to high doses of methylprednisolone. Only one patient had anti-GFAP ABs with a typical staining pattern of astrocytes, whereas serum and CSF of the other patient were negative and showed neither reactivity to brain tissue nor to vital or permeabilized astrocytes. Neuropathologic examination of the anti-GFAP AB-negative patient revealed infiltration of macrophages and T cells around blood vessels and activation of microglia without obvious features of clasmatodendrosis.</AbstractText>The GFAP-AB negative patient had both a striking (para)clinical similarity and an immediate response to immunotherapy. This supports the hypothesis that the clinical spectrum of steroid-responsive meningoencephalomyelitis suggestive of autoimmune GFAP astrocytopathy may be broader and may comprise also seronegative cases.</AbstractText>Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.</CopyrightInformation> |
2,328,053 | Hypercholesterolemia negatively influences morphology and molecular markers of epithelial cells within the choroid plexus in rabbits. | Choroid plexus (CP) is an important tissue not only to produce cerebrospinal fluid (CSF) but also to regulate substances that are secreted into or absorbed from CSF through blood-cerebrospinal fluid barrier (BCSFB) formed by CP epithelial cells (CPECs). CPECs display signs of deterioration in aged and diseased people. However, whether CPECs in hypercholesterolemic animals develop such damage is not known.</AbstractText>We used cholesterol-fed wild-type or Watanabe hereditary hyperlipidemic (WHHL) rabbits of identical age to determine CPEC changes in terms of morphology and protein expression/localization.</AbstractText>Compared with non-cholesterol-fed control rabbits, prolonged exposure to cholesterol reduced CPEC height and increased lipofuscin levels in CPECs, indicating cellular damage. Expression of aquaporin 1 on the apical membranes of CPECs was diminished in cholesterol-exposed rabbits, implying a reduced CSF-producing function in the CP. The rabbit macrophage-specific antibody (RAM11) immunoreaction became positive in CPECs adjacent to foam cells, indicating an alteration in this cell type.</AbstractText>Cholesterol insults from the circulation (which is reflected by foam-cell accumulation in the CP) induce CPEC dysfunction, and the latter seems to be enhanced by foam cells in hypercholesterolemic rabbits.</AbstractText> |
2,328,054 | Verification of the Deep Brain Stimulation Electrode Position Using Intraoperative Electromagnetic Localization. | Electromagnetic (EM) localization has typically been used to direct shunt catheters into the ventricle. The objective of this study was to determine if this method of EM tracking could be used in a deep brain stimulation (DBS) electrode cannula to accurately predict the eventual location of the electrode contacts.</AbstractText>The Medtronic AxiEMTM system was used to generate the cannula tip location directed to the planned target site. Prior to clinical testing, a series of phantom modelling observations were made.</AbstractText>Phantom trials (n = 23) demonstrated that the cannula tip could be accurately located at the target site with an error of between 0.331 ± 0.144 and 0.6 ± 0.245 mm, depending on the orientation of the delivery system to the axis of the phantom head. Intraoperative EM localization of the DBS cannula was performed in 84 trajectories in 48 patients. The average difference between the planned target and the EM stylet location at the cannula tip was 1.036 ± 0.543 mm. The average error between the planned target coordinates and the actual target electrode location (by CT) was 1.431 ± 0.607 and 1.145 ± 0.636 mm for the EM stylet location in the cannula (p = 0.00312), indicating that EM localization reflected the position of the target electrode more accurately than the planned target.</AbstractText>EM localization can be used to verify the position of DBS electrodes intraoperatively with a high accuracy.</AbstractText>© 2020 S. Karger AG, Basel.</CopyrightInformation> |
2,328,055 | Correlation of optic nerve and optic nerve sheath diameter with intracranial pressure in pigs. | Several studies have shown an association between intracranial pressure and the diameter of the optic nerve sheath measured by transbulbar ultrasonography. To understand the pathophysiology of this phenomenon, we aimed to measure the changes of the optic nerve, optic nerve sheath and perineural space separately with increasing intracranial pressure in a porcine model.</AbstractText>An external ventricular drain was placed into the third ventricle through a right paramedian burrhole in eight anesthesized pigs. The diameters of the optic nerve and the optic nerve sheath were measured while the intracranial pressure (ICP) was increased in steps of 10mmHg from baseline up to 60 mmHg.</AbstractText>The median diameters of the optic nerve (ON) increased from 0.36 cm (baseline- 95% confidence interval (CI) 0.33 cm to 0.45 cm) to 0.68 cm (95% CI 0.57 cm to 0.82 cm) at ICP of 60 mmHg (p<0.0001) and optic nerve sheath (ONS) from 0.88 cm (95% CI 0.79 cm to 0.98 cm) to 1.24 cm (95% CI 1.02 cm to 1.38 cm) (p< 0.002) while the median diameter of the perineural space (PNS) (baseline diameter 95% CI 0.40 cm to 0.59 cm to diameters at ICP 60 95% CI 0.38 cm to 0.62 cm) did not change significantly (p = 0.399). Multiple comparisons allowed differentiation between baseline and values ≥40 mmHg for ON (p = 0.017) and between baseline and values ≥ 50mmHg for ONS (p = 0.006). A linear correlation between ON (R2 = 0.513, p<0.0001) and ONS (R2 = 0.364, p<0.0001) with ICP was found. The median coefficient of variation for intra- and inter-investigator variability was 8% respectively 2.3%.</AbstractText>Unexpectedly, the increase in ONS diameter with increasing ICP is exclusively related to the increase of the diameter of the ON. Further studies should explore the reasons for this behaviour.</AbstractText> |
2,328,056 | Transcallosal Interforniceal Approach for a Large Choroid Plexus Tumor in a 4-Month-Old Boy: 2-Dimensional Operative Video. | Tumors in the third ventricle constitute a challenge for the neurosurgeon, regardless of the chosen approach. The additional risk of severe blood loss in the pediatric population, specially for choroid plexus tumors, which are the most common ventricular tumors in children, adds a significant challenge in these cases. Therefore, a careful selection of the approach in addition to surgical technique is crucial for a favorable outcome. In this video, we discuss the approach selected for the treatment of a large choroid plexus tumor in a 4-mo-old male and highlight the surgical technique chosen for this case, a transcallosal interforniceal approach.1 Appropriate consent for the video authorization and the procedure was obtained from the parent of the patient. Images in video from Rhoton AL Jr, The Cerebrum, Neurosurgery, 2007, 61, suppl_1, SHC-37-SHC-119, by permission of the Congress of Neurological Surgeons. |
2,328,057 | Prenatal detection of chromosomal abnormalities and copy number variants in fetuses with ventriculomegaly. | To systematically investigate chromosomal abnormalities and copy number variants (CNVs) in fetuses with different types of ventriculomegaly (VM) by karyotyping and/or chromosomal microarray analysis (CMA).</AbstractText>This retrospective study included 312 fetuses diagnosed with VM. Amniotic fluid and umbilical blood samples were collected by amniocentesis and cordocentesis, respectively, and subjected to karyotyping and/or CMA. Subgroup analysis by VM type, including mild VM (MVM) and severe VM (SVM), unilateral and bilateral VM, isolated VM (IVM), and non-isolated VM (NIVM), was performed.</AbstractText>The detection rate of chromosomal abnormalities was 12.1% (34/281) by karyotyping and 20.6% when CMA was additionally performed (P < 0.05). Abnormalities were identified by CMA in 17.4% (38/218) of fetuses and pathogenic CNVs in 5.0% (11/218). Notably, CMA detected CNVs in 10.6% (23/218) of fetuses with normal karyotypes. The incidence of chromosomal abnormalities by karyotyping was higher in bilateral than in unilateral VM (20.5% versus 6.5%), whereas the incidence detected by CMA was higher in NIVM than in IVM (21.4% versus 10.3%; both P < 0.05). In NIVM, CMA provided an additional detection rate of 11.4% (16/140) and a detection rate of 10.0% for pathogenic CNVs and aneuploidies. Central nervous system (CNS) abnormalities were the most common other ultrasonic abnormalities.</AbstractText>CMA is highly recommended for prenatal diagnosis of fetal VM together with karyotyping, especially in fetuses with bilateral VM and NIVM with abnormal CNS findings. Further study is necessary to explore the relationships between genotypes and phenotypes to facilitate prenatal diagnosis of fetal VM.</AbstractText>Copyright © 2020 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.</CopyrightInformation> |
2,328,058 | Inflammation of the choroid plexus in progressive multiple sclerosis: accumulation of granulocytes and T cells. | The choroid plexus (CP) is strategically located between the peripheral blood and the cerebrospinal fluid, and is involved in the regulation of central nervous system (CNS) homeostasis. In multiple sclerosis (MS), demyelination and inflammation occur in the CNS. While experimental animal models of MS pointed to the CP as a key route for immune cell invasion of the CNS, little is known about the distribution of immune cells in the human CP during progressive phases of MS. Here, we use immunohistochemistry and confocal microscopy to explore the main immune cell populations in the CP of progressive MS patients and non-neuroinflammatory controls, in terms of abundance and location within the distinct CP compartments. We show for the first time that the CP stromal density of granulocytes and CD8+ T cells is higher in progressive MS patients compared to controls. In line with previous studies, the CP of both controls and progressive MS patients contains relatively high numbers of macrophages and dendritic cells. Moreover, we found virtually no B cells or plasma cells in the CP. MHCII+ antigen-presenting cells were often found in close proximity to T cells, suggesting constitutive CNS immune monitoring functions of the CP. Together, our data highlights the role of the CP in immune homeostasis and indicates the occurrence of mild inflammatory processes in the CP of progressive MS patients. However, our findings suggest that the CP is only marginally involved in immune cell migration into the CNS in chronic MS. |
2,328,059 | Normal right and left ventricular volumes prospectively obtained from cardiovascular magnetic resonance in awake, healthy, 0- 12 year old children. | Pediatric z scores are necessary to describe size and structure of the heart in growing children, however, development of an accurate z score calculator requires robust normal datasets, which are difficult to obtain with cardiovascular magnetic resonance (CMR) in children. Motion-corrected (MOCO) cines from re-binned, reconstructed real-time cine offer a free-breathing, rapid acquisition resulting in cines with high spatial and temporal resolution. In combination with child-friendly positioning and entertainment, MOCO cine technique allows for rapid cine volumetry in patients of all ages without sedation. Thus, our aim was to prospectively enroll normal infants and children birth-12 years for creation and validation of a z score calculator describing normal right ventricular (RV) and left ventricular (LV) size.</AbstractText>With IRB approval and consent/assent, 149 normal children successfully underwent a brief noncontrast CMR on a 1.5 T scanner including MOCO cines in the short axis, and RV and LV volumes were measured. 20% of scans were re-measured for interobserver variability analyses. A general linear modeling (GLM) framework was employed to identify and properly represent the relationship between CMR-based assessments and anthropometric data. Scatter plots of model fit and Akaike's information criteria (AIC) results were used to guide the choice among alternative models.</AbstractText>A total of 149 subjects aged 22 days-12 years (average 5.1 ± 3.6 years), with body surface area (BSA) range 0.21-1.63 m2</sup> (average 0.8 ± 0.35 m2</sup>) were scanned. All ICC values were > 95%, reflecting excellent agreement between raters. The model that provided the best fit of volume measure to the data included BSA with higher order effects and gender as independent variables. Compared with earlier z score models, there is important additional growth inflection in early toddlerhood with similar z score prediction in later childhood.</AbstractText>Free-breathing, MOCO cines allow for accurate, reliable RV and LV volumetry in a wide range of infants and children while awake. Equations predicting fit between LV and RV normal values and BSA are reported herein for purposes of creating z scores.</AbstractText>clinicaltrials.gov NCT02892136, Registered 7/21/2016.</AbstractText> |
2,328,060 | The Interstitial System of the Brain in Health and Disease. | The brain interstitial fluid (ISF) and the cerebrospinal fluid (CSF) cushion and support the brain cells. The ISF occupies the brain interstitial system (ISS), whereas the CSF fills the brain ventricles and the subarachnoid space. The brain ISS is an asymmetrical, tortuous, and exceptionally confined space between neural cells and the brain microvasculature. Recently, with a newly developed <i>in vivo</i> measuring technique, a series of discoveries have been made in the brain ISS and the drainage of ISF. The goal of this review is to confer recent advances in our understanding of the brain ISS, including its structure, function, and the various processes mediating or disrupting ISF drainage in physiological and pathological conditions. The brain ISF in the deep brain regions has recently been demonstrated to drain in a compartmentalized ISS instead of a highly connected system, together with the drainage of ISF into the cerebrospinal fluid (CSF) at the surface of the cerebral cortex and the transportation from CSF into cervical lymph nodes. Besides, accumulation of tau in the brain ISS in conditions such as Alzheimer's disease and its link to the sleep-wake cycle and sleep deprivation, clearance of ISF in a deep sleep via increased CSF flow, novel approaches to remove beta-amyloid from the brain ISS, and obstruction to the ISF drainage in neurological conditions are deliberated. Moreover, the role of ISS in the passage of extracellular vesicles (EVs) released from neural cells and the rapid targeting of therapeutic EVs into neural cells in the entire brain following an intranasal administration, and the promise and limitations of ISS based drug delivery approaches are discussed. |
2,328,061 | Cardiovascular Comorbidity in Patients with Chronic Obstructive Pulmonary Disease: Echocardiography Changes and Their Relation to the Level of Airflow Limitation.<Pagination><StartPage>3568</StartPage><EndPage>3573</EndPage><MedlinePgn>3568-3573</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.3889/oamjms.2019.848</ELocationID><Abstract><AbstractText Label="AIM" NlmCategory="OBJECTIVE">To compare the frequency of echocardiographic changes in patients with chronic obstructive pulmonary disease (COPD) and non-COPD controls and to assess their relation to the level of airflow limitation.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">Study population included 120 subjects divided into two groups. Group 1 included 60 patients with COPD (52 male and 8 females, aged 40 to 80 years) initially diagnosed according to the actual recommendations. Group 2 included 60 subjects in whom COPD was excluded serving as a control. The study protocol consisted of completion of a questionnaire, pulmonary evaluation (dyspnea severity assessment, baseline and post-bronchodilator spirometry, gas analyses, and chest X-ray) and two dimensional (2D) Doppler echocardiography.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">We found significantly higher mean right ventricle end-diastolic dimension (RVEDd) in COPD patients as compared to its dimension in controls (28.0 ± 4.8 mm vs. 24.4 ± 4.3 mm; P = 0.0000). Pulmonary hypertension (PH) was more frequent in COPD patients than in controls (33.3% vs. 0%; P = 0.0004) showing a linear relationship with the severity of airflow limitation. The mean value of left ventricular ejection fraction (LVEF%) was significantly lower in COPD patients than its mean value in controls (57.4 ± 6.9% vs 64.8 ± 2.7%; P = 0.0000) with no correlation with severity of airflow limitation.</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">Frequency of echocardiographic changes in COPD patients was significantly higher as compared to their frequency in controls in the most cases being significantly associated with the severity of airflow limitation. Echocardiography enables early, noninvasive, and accurate diagnosis of cardiac changes in COPD patients giving time for early intervention.</AbstractText><CopyrightInformation>Copyright: © 2019 Daniela Buklioska-Ilievska, Jordan Minov, Nade Kochovska-Kamchevska, Biljana Prgova-Veljanova, Natasha Petkovikj, Vladimir Ristovski, Marjan Baloski.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Buklioska-Ilievska</LastName><ForeName>Daniela</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>General Hospital, "8th September", Skopje, Republic of Macedonia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Minov</LastName><ForeName>Jordan</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Institute for Occupational Health of Republic of Macedonia - WHO Collaborating Center, Skopje, Republic of Macedonia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kochovska-Kamchevska</LastName><ForeName>Nade</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>General Hospital, "8th September", Skopje, Republic of Macedonia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Prgova-Veljanova</LastName><ForeName>Biljana</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>General Hospital, "8th September", Skopje, Republic of Macedonia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Petkovikj</LastName><ForeName>Natasha</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>General Hospital, "8th September", Skopje, Republic of Macedonia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ristovski</LastName><ForeName>Vladimir</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>General Hospital, "8th September", Skopje, Republic of Macedonia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Baloski</LastName><ForeName>Marjan</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>General Hospital, "8th September", Skopje, Republic of Macedonia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>10</Month><Day>14</Day></ArticleDate></Article><MedlineJournalInfo><Country>North Macedonia</Country><MedlineTA>Open Access Maced J Med Sci</MedlineTA><NlmUniqueID>101662294</NlmUniqueID><ISSNLinking>1857-9655</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Airflow limitation</Keyword><Keyword MajorTopicYN="N">Chronic obstructive pulmonary disease</Keyword><Keyword MajorTopicYN="N">Doppler echocardiography</Keyword><Keyword MajorTopicYN="N">Pulmonary hypertension</Keyword><Keyword MajorTopicYN="N">Ventricular dysfunction</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>8</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2019</Year><Month>9</Month><Day>24</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>9</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>2</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>2</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>2</Month><Day>6</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32010378</ArticleId><ArticleId IdType="pmc">PMC6986525</ArticleId><ArticleId IdType="doi">10.3889/oamjms.2019.848</ArticleId><ArticleId IdType="pii">OAMJMS-7-3568</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Sabit R, Bolton C. 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Egyptian Journal of Chest Diseases and Tuberculosis. 2013;62:575–582. https://doi.org/10.1016/j.ejcdt.2013.08.004.</Citation></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">32009647</PMID><DateCompleted><Year>2020</Year><Month>09</Month><Day>04</Day></DateCompleted><DateRevised><Year>2021</Year><Month>09</Month><Day>11</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1940-087X</ISSN><JournalIssue CitedMedium="Internet"><Issue>155</Issue><PubDate><Year>2020</Year><Month>Jan</Month><Day>17</Day></PubDate></JournalIssue><Title>Journal of visualized experiments : JoVE</Title><ISOAbbreviation>J Vis Exp</ISOAbbreviation></Journal>Generation of Ventricular-Like HiPSC-Derived Cardiomyocytes and High-Quality Cell Preparations for Calcium Handling Characterization.<ELocationID EIdType="doi" ValidYN="Y">10.3791/60135</ELocationID><Abstract><AbstractText>Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) provide a valuable human source for studying the basic science of calcium (Ca<sup>2+</sup>) handling and signaling pathways as well as high-throughput drug screening and toxicity assays. Herein, we provide a detailed description of the methodologies used to generate high-quality iPSC-CMs that can consistently reproduce molecular and functional characteristics across different cell lines. Additionally, a method is described to reliably assess their functional characterization through the evaluation of Ca<sup>2+</sup> handling properties. Low oxygen (O2) conditions, lactate selection, and prolonged time in culture produce high-purity and high-quality ventricular-like cardiomyocytes. Similar to isolated adult rat cardiomyocytes (ARCMs), 3-month-old iPSC-CMs exhibit higher Ca<sup>2+</sup> amplitude, faster rate of Ca<sup>2+</sup> reuptake (decay-tau), and a positive lusitropic response to β-adrenergic stimulation compared to day 30 iPSC-CMs. The strategy is technically simple, cost-effective, and reproducible. It provides a robust platform to model cardiac disease and for the large-scale drug screening to target Ca<sup>2+</sup> handling proteins.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Oh</LastName><ForeName>Jae Gyun</ForeName><Initials>JG</Initials><AffiliationInfo><Affiliation>Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dave</LastName><ForeName>Jaydev</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kho</LastName><ForeName>Changwon</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stillitano</LastName><ForeName>Francesca</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai; francesca.stillitano@mssm.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>KL2 TR001435</GrantID><Acronym>TR</Acronym><Agency>NCATS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R00 HL116645</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D059040">Video-Audio Media</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>01</Month><Day>17</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Vis Exp</MedlineTA><NlmUniqueID>101313252</NlmUniqueID><ISSNLinking>1940-087X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>SY7Q814VUP</RegistryNumber><NameOfSubstance UI="D002118">Calcium</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002118" MajorTopicYN="N">Calcium</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002454" MajorTopicYN="N">Cell Differentiation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006352" MajorTopicYN="N">Heart Ventricles</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="Y">cytology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D057026" MajorTopicYN="N">Induced Pluripotent Stem Cells</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="Y">cytology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D032383" MajorTopicYN="N">Myocytes, Cardiac</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="Y">cytology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017207" MajorTopicYN="N">Rats, Sprague-Dawley</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013997" MajorTopicYN="N">Time Factors</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>2</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>2</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>9</Month><Day>5</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32009647</ArticleId><ArticleId IdType="doi">10.3791/60135</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">32009641</PMID><DateCompleted><Year>2020</Year><Month>09</Month><Day>04</Day></DateCompleted><DateRevised><Year>2020</Year><Month>09</Month><Day>04</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1940-087X</ISSN><JournalIssue CitedMedium="Internet"><Issue>155</Issue><PubDate><Year>2020</Year><Month>Jan</Month><Day>17</Day></PubDate></JournalIssue><Title>Journal of visualized experiments : JoVE</Title><ISOAbbreviation>J Vis Exp</ISOAbbreviation></Journal>Optical Imaging of Isolated Murine Ventricular Myocytes. | Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) provide a valuable human source for studying the basic science of calcium (Ca<sup>2+</sup>) handling and signaling pathways as well as high-throughput drug screening and toxicity assays. Herein, we provide a detailed description of the methodologies used to generate high-quality iPSC-CMs that can consistently reproduce molecular and functional characteristics across different cell lines. Additionally, a method is described to reliably assess their functional characterization through the evaluation of Ca<sup>2+</sup> handling properties. Low oxygen (O2) conditions, lactate selection, and prolonged time in culture produce high-purity and high-quality ventricular-like cardiomyocytes. Similar to isolated adult rat cardiomyocytes (ARCMs), 3-month-old iPSC-CMs exhibit higher Ca<sup>2+</sup> amplitude, faster rate of Ca<sup>2+</sup> reuptake (decay-tau), and a positive lusitropic response to β-adrenergic stimulation compared to day 30 iPSC-CMs. The strategy is technically simple, cost-effective, and reproducible. It provides a robust platform to model cardiac disease and for the large-scale drug screening to target Ca<sup>2+</sup> handling proteins.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Oh</LastName><ForeName>Jae Gyun</ForeName><Initials>JG</Initials><AffiliationInfo><Affiliation>Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dave</LastName><ForeName>Jaydev</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kho</LastName><ForeName>Changwon</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stillitano</LastName><ForeName>Francesca</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai; francesca.stillitano@mssm.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>KL2 TR001435</GrantID><Acronym>TR</Acronym><Agency>NCATS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R00 HL116645</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D059040">Video-Audio Media</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>01</Month><Day>17</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Vis Exp</MedlineTA><NlmUniqueID>101313252</NlmUniqueID><ISSNLinking>1940-087X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>SY7Q814VUP</RegistryNumber><NameOfSubstance UI="D002118">Calcium</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002118" MajorTopicYN="N">Calcium</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002454" MajorTopicYN="N">Cell Differentiation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002478" MajorTopicYN="N">Cells, Cultured</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006352" MajorTopicYN="N">Heart Ventricles</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="Y">cytology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D057026" MajorTopicYN="N">Induced Pluripotent Stem Cells</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="Y">cytology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D032383" MajorTopicYN="N">Myocytes, Cardiac</DescriptorName><QualifierName UI="Q000166" MajorTopicYN="Y">cytology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017207" MajorTopicYN="N">Rats, Sprague-Dawley</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013997" MajorTopicYN="N">Time Factors</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>2</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>2</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>9</Month><Day>5</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32009647</ArticleId><ArticleId IdType="doi">10.3791/60135</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">32009641</PMID><DateCompleted><Year>2020</Year><Month>09</Month><Day>04</Day></DateCompleted><DateRevised><Year>2020</Year><Month>09</Month><Day>04</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1940-087X</ISSN><JournalIssue CitedMedium="Internet"><Issue>155</Issue><PubDate><Year>2020</Year><Month>Jan</Month><Day>17</Day></PubDate></JournalIssue><Title>Journal of visualized experiments : JoVE</Title><ISOAbbreviation>J Vis Exp</ISOAbbreviation></Journal><ArticleTitle>Optical Imaging of Isolated Murine Ventricular Myocytes.</ArticleTitle><ELocationID EIdType="doi" ValidYN="Y">10.3791/60196</ELocationID><Abstract>The ability to isolate adult cardiac myocytes has permitted researchers to study a variety of cardiac pathologies at the single cell level. While advances in calcium sensitive dyes have permitted the robust optical recording of single cell calcium dynamics, recording of robust transmembrane optical voltage signals has remained difficult. Arguably, this is because of the low single to noise ratio, phototoxicity, and photobleaching of traditional potentiometric dyes. Therefore, single cell voltage measurements have long been confined to the patch clamp technique which while the gold standard, is technically demanding and low throughput. However, with the development of novel potentiometric dyes, large, fast optical responses to changes in voltage can be obtained with little to no phototoxicity and photobleaching. This protocol describes in detail how to isolate adult murine myocytes which can be used for cellular shortening, calcium, and optical voltage measurements. Specifically, the protocol describes how to use a ratiometric calcium dye, a single-excitation calcium dye, and a single excitation voltage dye. This approach can be used to assess the cardiotoxicity and arrhythmogenicity of various chemical agents. While phototoxicity is still an issue at the single cell level, methodology is discussed on how to reduce it. |
2,328,062 | Pathogenic and Uncertain Genetic Variants Have Clinical Cardiac Correlates in Diverse Biobank Participants. | Background Genome sequencing coupled with electronic heath record data can uncover medically important genetic variation. Interpretation of rare genetic variation and its role in mediating cardiovascular phenotypes is confounded by variants of uncertain significance. Methods and Results We analyzed the whole genome sequence of 900 racially and ethnically diverse biobank participants selected from a single US center. Participants were equally divided among European, African, Hispanic, and mixed races/ethnicities. We evaluated the American College of Medical Genetics and Genomics medically actionable list of 59 genes, focusing on the cardiac genes. Variation was interpreted using the most recent reports in ClinVar, a database of medically relevant human variation. We identified 19 individuals with pathogenic or likely pathogenic variants in cardiac actionable genes (2%) and found evidence of related clinical correlates in the electronic health record. Participants of African ancestry, compared with those of European ancestry, had more variants of uncertain significance in the medically actionable genes including the 30 cardiac actionable genes, even when normalized to total variant count per person. Longitudinal measures of left ventricle size from ≈400 biobank participants (1723 patient-years) were correlated with genetic findings. The presence of ≥1 uncertain variant in the actionable cardiac genes and a cardiomyopathy diagnosis correlated with increased left ventricular internal diameter in diastole and in systole. In particular, <i>MYBPC3</i> was identified as a gene with excess variants of uncertain significance. Conclusions These data indicate that a subset of uncertain genetic variants may confer risk and should not be considered benign. |
2,328,063 | Ependyma-expressed CCN1 restricts the size of the neural stem cell pool in the adult ventricular-subventricular zone. | Adult neural stem cells (NSCs) reside in specialized niches, which hold a balanced number of NSCs, their progeny, and other cells. How niche capacity is regulated to contain a specific number of NSCs remains unclear. Here, we show that ependyma-derived matricellular protein CCN1 (cellular communication network factor 1) negatively regulates niche capacity and NSC number in the adult ventricular-subventricular zone (V-SVZ). Adult ependyma-specific deletion of Ccn1 transiently enhanced NSC proliferation and reduced neuronal differentiation in mice, increasing the numbers of NSCs and NSC units. Although proliferation of NSCs and neurogenesis seen in Ccn1 knockout mice eventually returned to normal, the expanded NSC pool was maintained in the V-SVZ until old age. Inhibition of EGFR signaling prevented expansion of the NSC population observed in CCN1 deficient mice. Thus, ependyma-derived CCN1 restricts NSC expansion in the adult brain to maintain the proper niche capacity of the V-SVZ. |
2,328,064 | Characterization of the circadian oscillator in the choroid plexus of rats. | Circadian rhythms are a fundamental biological phenomena that control various physiological functions. The suprachiasmatic nucleus (SCN) is a master clock that integrates various peripheral clocks. Recently, the choroid plexus (CP) was reported to be one such peripheral clock, a circadian oscillator that might conversely affect the SCN. Hence, the principle aim of our study was to unravel the circadian oscillator within the CP. Quantitative PCR against rPer1, rPer2, and rBmal1 showed that CP in the lateral ventricle (CP-LV) and fourth ventricle (CP-4V) has a robust circadian oscillator. The phases of the CP oscillator are between those of the pineal gland (PG) and SCN. Bioluminescence monitoring of explants showed that the intrinsic circadian period of CP-LV and CP-4V was approximately 21 h, which is shorter than SCN and PG. It is possible that interaction between oscillators of the CP-LV, CP-4V, PG, and SCN ensures the SCN adopts a stable 24 h rhythm, with each of the regions having an intrinsic oscillator with different phases and periods. In situ hybridization analysis revealed that dusk-to-dawn variation of rPer2 expression was found in epithelial cells of the CP only. Furthermore, the CP circadian oscillator might control cerebrospinal fluid secretion. However, no dusk-to-dawn variation in expression of the water channel, aquaporin 1, was observed. Further investigations are needed to clarify the involvement of circadian rhythm on CP. |
2,328,065 | Human CD4<sup>+</sup> T cell subsets differ in their abilities to cross endothelial and epithelial brain barriers in vitro. | The brain barriers establish compartments in the central nervous system (CNS) that significantly differ in their communication with the peripheral immune system. In this function they strictly control T-cell entry into the CNS. T cells can reach the CNS by either crossing the endothelial blood-brain barrier (BBB) or the epithelial blood-cerebrospinal fluid barrier (BCSFB) of the choroid plexus (ChP).</AbstractText>Analysis of the cellular and molecular mechanisms involved in the migration of different human CD4+</sup> T-cell subsets across the BBB versus the BCSFB.</AbstractText>Human in vitro models of the BBB and BCSFB were employed to study the migration of circulating and CNS-entry experienced CD4+</sup> T helper cell subsets (Th1, Th1*, Th2, Th17) across the BBB and BCSFB under inflammatory and non-inflammatory conditions in vitro.</AbstractText>While under non-inflammatory conditions Th1* and Th1 cells preferentially crossed the BBB, under inflammatory conditions the migration rate of all Th subsets across the BBB was comparable. The migration of all Th subsets across the BCSFB from the same donor was 10- to 20-fold lower when compared to their migration across the BBB. Interestingly, Th17 cells preferentially crossed the BCSFB under both, non-inflamed and inflamed conditions. Barrier-crossing experienced Th cells sorted from CSF of MS patients showed migratory characteristics indistinguishable from those of circulating Th cells of healthy donors. All Th cell subsets could additionally cross the BCSFB from the CSF to ChP stroma side. T-cell migration across the BCSFB involved epithelial ICAM-1 irrespective of the direction of migration.</AbstractText>Our observations underscore that different Th subsets may use different anatomical routes to enter the CNS during immune surveillance versus neuroinflammation with the BCSFB establishing a tighter barrier for T-cell entry into the CNS compared to the BBB. In addition, CNS-entry experienced Th cell subsets isolated from the CSF of MS patients do not show an increased ability to cross the brain barriers when compared to circulating Th cell subsets from healthy donors underscoring the active role of the brain barriers in controlling T-cell entry into the CNS. Also we identify ICAM-1 to mediate T cell migration across the BCSFB.</AbstractText> |
2,328,066 | Brain Volumes of very Low Birth Weight Infants Measured by Two-dimensional Cranial Ultrasonography: A Prospective Cohort Study. | Cranial ultrasonography is the main neuroimaging technique for very low birth weight infants. Low brain volume is associated with poor neurologic outcome. This study aimed to calculate brain volumes of preterm infants with two-dimensional measurements of cranial ultrasonography.</AbstractText>Intracranial height, anteroposterior diameter, bi-parietal diamater, ventricular height, thalamo-occipital distance and ventricular index were measured with routine cranial ultrasonographic scanning. Brain considered a spheric, ellipsoid model and estimated brain volume (EBV) was calculated by subtracting two lateral ventricular volumes from the total brain volume.</AbstractText>One hundred and twenty-one preterm infants under a birth weight of 1500 g and 32 weeks of gestational age were included in this study. The mean gestational age of study population was 27.7 weeks, and mean birthweight was 1057 grams. Twenty-two of 121 infants had dilated ventricle, in this group, EBV was lower than normal group (202 ± 58 cm3 vs 250 ± 53 cm3, respectively, p<0.01). Advanced resuscitation, bronchopulmonary dysplasia and late-onset sepsis were found to be independent risk factors for low brain volume in our data.</AbstractText>Estimated brain volume can be calculated by two-dimensional measurements with cranial ultrasonography.</AbstractText>Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.</CopyrightInformation> |
2,328,067 | A new index for assessing cerebral ventricular volume in idiopathic normal-pressure hydrocephalus: a comparison with Evans' index. | To recommend a new simple and explicit index termed the anteroposterior diameter of the lateral ventricle index (ALVI) for assessing brain ventricular size in neuroimaging and to compare Evans index (EI) between idiopathic normal pressure hydrocephalus (iNPH) patients and age-matched healthy elderly subjects.</AbstractText>Retrospective measurements of ventricular volume (VV), relative VV (RVV), the EI, and the ALVI were taken from thin-section CT scans for 23 pre-shunt-insertion iNPH patients and 62 age-matched healthy elderly volunteers. The area under the receiver operating characteristic (ROC) curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to assess the effectiveness of ALVI scores for predicting VV.</AbstractText>The correlations between VV or RVV and ALVI scores (VV, r = 0.957; RVV, r = 0.983) were significantly stronger than the corresponding correlations with EI scores (VV, r = 0.843; RVV, r = 0.840). The AUC for ALVI scores was significantly greater than the AUC for EI scores. Furthermore, with the inclusion of the ALVI, the NRI value was 0.14 and the IDI value was 0.14; these improvements were also statistically significant.</AbstractText>The ALVI is a more accurate and more explicitly defined marker of VV than the EI and assesses ventricular enlargement effectively. We suggest that ventricular enlargement of the healthy elderly be defined by ALVI > 0.50.</AbstractText> |
2,328,068 | Fibrinogen induces neural stem cell differentiation into astrocytes in the subventricular zone via BMP signaling. | Neural stem/progenitor cells (NSPCs) originating from the subventricular zone (SVZ) contribute to brain repair during CNS disease. The microenvironment within the SVZ stem cell niche controls NSPC fate. However, extracellular factors within the niche that trigger astrogliogenesis over neurogenesis during CNS disease are unclear. Here, we show that blood-derived fibrinogen is enriched in the SVZ niche following distant cortical brain injury in mice. Fibrinogen inhibited neuronal differentiation in SVZ and hippocampal NSPCs while promoting astrogenesis via activation of the BMP receptor signaling pathway. Genetic and pharmacologic depletion of fibrinogen reduced astrocyte formation within the SVZ after cortical injury, reducing the contribution of SVZ-derived reactive astrocytes to lesion scar formation. We propose that fibrinogen is a regulator of NSPC-derived astrogenesis from the SVZ niche via BMP receptor signaling pathway following injury. |
2,328,069 | Comparison on epidemiology, tumor location, histology, and prognosis of intracranial germ cell tumors between Mayo Clinic and Japanese consortium cohorts. | Central nervous system (CNS) germ cell tumors (GCTs) are rare malignant neoplasms that arise predominantly in adolescents and young adults. CNS GCTs demonstrate characteristic trends in national associations, with implications for both tumor incidence and genetics. Although the incidence of CNS GCTs is markedly higher in East Asia than Western countries, direct comparative analyses between these CNS GCT populations are limited.</AbstractText>In Japan, to facilitate the genomic analyses of CNS GCTs, the Intracranial Germ Cell Tumor Genome Analysis Consortium was established in 2011, and more than 200 cases of GCTs are available for both tumor tissue and clinical data, which is organized by the National Cancer Center (NCC) Japan. At the Mayo Clinic, there have been 98 cases of intracranial GCTs treated by the Department of Neurologic Surgery since 1988. In this paper, the authors compared the epidemiology, clinical presentation including location and histology, and prognosis between cases treated in the US and Japan.</AbstractText>There was no significant difference in age and sex distributions between the databases. However, there was a significant difference in the tumor locations; specifically, the frequency of basal ganglia was higher in the NCC database compared with the Mayo Clinic (8.4% vs 0%, p = 0.008), and bifocal location (neurohypophysis and pineal gland) was higher at the Mayo Clinic than at the NCC (18.8% vs 5.8%, p = 0.002). There was no difference in histological subdivisions between the databases. There was no difference in progression-free survival (PFS) and overall survival (OS) of germinoma cases and OS of nongerminomatous GCT (NGGCT) cases treated with chemotherapy and radiation therapy covering whole ventricles. However, PFS of NGGCTs differed significantly, and was better in the NCC cohorts (p = 0.04).</AbstractText>There appears to be a differential distribution of GCTs by neuroanatomical location between major geographic and national groups. Further study is warranted to better characterize any underlying genomic, epigenetic, or environmental factors that may be driving the phenotypic differences.</AbstractText> |
2,328,070 | Condition of hemodynamics in the pulmonary circulation of patients with chronic obstructive pulmonary disease (copd) concurrent with metabolic syndrome with hypertrophy and atrophy of the myocardium. | In recent years, COPD is observed as not an isolated, but an associated pathology, in particular, concurrent with metabolic syndrome. The aim of the research is to identify the differences in changes of the rheopulmonography parameters (RPG) depending on the presence of hypertrophy or atrophy of the right ventricular myocardium in patients with COPD concurrent with metabolic syndrome.</AbstractText>We studied changes in rheopulmonography (RPG) in 145 patients with chronic obstructive pulmonary disease (COPD) concurrent with metabolic syndrome.</AbstractText>We detected precapillary hypertension of the pulmonary circulation in patients with right ventricular myocardial hypertrophy: anacrotism serration; flattened peak of the systolic wave; decreased Vcp; high placement of incisura; horizontal course of catacrotism; decreased amplitude of the systolic wave (in this case, due to a greater increase in the resistance of the blood flow in the pulmonary vessels than the decreased impact volume of the right ventricle); prolonged Q-a (in this group of patients, it depends more on hypertension of the pulmonary circulation than on the reduction of contractile function of the myocardium). In atrophy of the right ventricular myocardium, the following changes in the RPG were revealed: decreased systolic wave at its dramatic rise; prolonged Q-a (in this case, due to the weakened heart contraction); Vmax reduction (it reflects the reduction of myocardial contractility); in hypertrophy of the myocardium, Vcp., unlike RPG, does not decrease, which is explained by the decrease in the pressure of the pulmonary circulation.</AbstractText>We believe that these changes in RPG allow differentiating hypertrophy and right ventricular myocardial atrophy along with established diagnostic criteria, and can be used as markers for the diagnosis and treatment of COPD concurrent with metabolic syndrome.</AbstractText> |
2,328,071 | Normal appearances and dimensions of the foetal cavum septi pellucidi and vergae on in utero MR imaging. | The aim of this study is to provide normative data about the appearances and dimensions of the cavum septi pellucidi and vergae (CSPV) on in utero MR (iuMR) imaging in second and third trimester foetuses.</AbstractText>Two hundred normal foetuses (from a low-risk pregnancy, with normal ante-natal USS findings and no intracranial abnormality of iuMR) had iuMR imaging between 18 and 37 gestational weeks (gw). The anatomical features on those studies were compared with published atlases of post-mortem foetal brains. The length, width and volume of the CSPV were measured in all foetuses.</AbstractText>The anatomy of the CSPV and its relationship with the corpus callosum and the fornices on iuMR imaging was comparable with post-mortem data at all gestational ages studied. The length of the CSPV increased throughout pregnancy, whereas the width and volume of CSPV reached a maximum between 29 and 31 gw and then showed a reduction later in pregnancy.</AbstractText>The iuMR imaging features of the CSPV and its close anatomical relations closely correspond to post-mortem data. The CSPV was patent in all cases but we have shown that closure commences in the midpart of the third trimester and advances in a posterior to anterior direction.</AbstractText> |
2,328,072 | Connexin Signaling Is Involved in the Reactivation of a Latent Stem Cell Niche after Spinal Cord Injury. | The ependyma of the adult spinal cord is a latent stem cell niche that is reactivated by spinal cord injury contributing new cells to the glial scar. The cellular events taking place in the early stages of the reaction of the ependyma to injury remain little understood. Ependymal cells are functionally heterogeneous with a mitotically active subpopulation lining the lateral domains of the central canal (CC) that are coupled via gap junctions. Gap junctions and connexin hemichannels are key regulators of the biology of neural progenitors during development and in adult neurogenic niches. Thus, we hypothesized that communication via connexins in the CC is developmentally regulated and may play a part in the reactivation of this latent stem cell niche after injury. To test these possibilities, we combined patch-clamp recordings of ependymal cells with immunohistochemistry for various connexins in the neonatal and the adult (P > 90) normal and injured spinal cord of male and female mice. We find that coupling among ependymal cells is downregulated as postnatal development proceeds but increases after injury, resembling the immature CC. The increase in gap junction coupling in the adult CC was paralleled by upregulation of connexin 26, which correlated with the resumption of proliferation and a reduction of connexin hemichannel activity. Connexin blockade reduced the injury-induced proliferation of ependymal cells. Our findings suggest that connexins are involved in the early reaction of ependymal cells to injury, representing a potential target to improve the contribution of the CC stem cell niche to repair.<b>SIGNIFICANCE STATEMENT</b> Ependymal cells in the adult spinal cord are latent progenitors that react to injury to support some degree of endogenous repair. Understanding the mechanisms by which these progenitor-like cells are regulated in the aftermath of spinal cord injury is critical to design future manipulations aimed at improving healing and functional recovery. Gap junctions and connexin hemichannels are key regulators of the biology of neural progenitors during development and in adult neurogenic niches. We find here that connexin signaling in the ependyma changes after injury of the adult spinal cord, functionally resembling the immature active-stem cell niche of neonatal animals. Our findings suggest that connexins in ependymal cells are potential targets to improve self-repair of the spinal cord. |
2,328,073 | Comparison of morphometric parameters in prediction of hydrocephalus using random forests. | Ventricles of the human brain enlarge with aging, neurodegenerative diseases, intrinsic, and extrinsic pathologies. The morphometric examination of neuroimages is an effective approach to assess structural changes occurring due to diseases such as hydrocephalus. In this study, we explored the effectiveness of commonly used morphological parameters in hydrocephalus diagnosis. For this purpose, the effect of six common morphometric parameters; Frontal Horns' Length (FHL), Maximum Lateral Length (MLL), Biparietal Diameter (BPD), Evans' Ratio (ER), Cella Media Ratio (CMR), and Frontal Horns' Ratio (FHR) were compared in terms of their importance in predicting hydrocephalus using a Random Forest classifier. The experimental results demonstrated that hydrocephalus can be detected with 91.46 % accuracy using all of these measurements. The accuracy of classification using only CMR and FHL reached up to 93.33 %. In terms of individual performances, CMR and FHL were the top performers whereas BPD and FHR did not contribute as much to the overall accuracy. |
2,328,074 | Longitudinal analysis of cerebral aqueduct flow measures: multiple sclerosis flow changes driven by brain atrophy. | Several small cross-sectional studies have investigated cerebrospinal fluid (CSF) flow dynamics in multiple sclerosis (MS) patients and have reported mixed results. Currently, there are no longitudinal studies that investigate CSF dynamics in MS patients.</AbstractText>To determine longitudinal changes in CSF dynamics measured at the level of aqueduct of Sylvius (AoS) in MS patients and matched healthy controls (HCs).</AbstractText>Forty (40) MS patients and 20 HCs underwent 3T MRI cine phase contrast imaging with velocity-encoded pulse-gated sequence at baseline and 5-year follow-up. For atrophy determination, MS patients underwent additional high-resolution 3D T1-weighted imaging. Measures of AoS cross-sectional area (CSA), average systolic and diastolic velocity peaks, maximal systolic and diastolic velocity peaks and average CSF flow rates were determined. Brain atrophy and ventricular CSF (vCSF) expansion rates were determined. Cross-sectional and longitudinal changes were derived by analysis of covariance (ANCOVA) and paired repeated tests. Confirmatory general linear models were also performed. False discovery rate (FDR)-corrected p-values lower than 0.05 were considered significant.</AbstractText>The MS population demonstrated significant increase in maximal diastolic peak (from 7.23 to 7.86 cm/s, non-adjusted p = 0.037), diastolic peak flow rate (7.76 ml/min to 9.33 ml/min, non-adjusted p = 0.023) and AoS CSA (from 3.12 to 3.69 mm2</sup>, adjusted p = 0.001). The only differentiator between MS patients and HCs was the greater AoS CSA (3.58 mm2</sup> vs. 2.57 mm2</sup>, age- and sex-adjusted ANCOVA, p = 0.045). The AoS CSA change was associated with vCSF expansion rate (age- and sex-adjusted Spearman's correlation r = 0.496, p = 0.019) and not with baseline nor change in maximal velocity. The expansion rate of the vCSF space explained an additional 23.8% of variance in change of AoS CSA variance when compared to age and sex alone (R2</sup> = 0.273, t = 2.557, standardized β = 0.51, and p = 0.019).</AbstractText>MS patients present with significant longitudinal AoS enlargement, potentially due to regional atrophy changes and ex-vacuo expansion of the aqueduct.</AbstractText> |
2,328,075 | Heart and Cardiac Substructure Dose Sparing in Synchronous Bilateral Breast Radiotherapy: A Dosimetric Study of Proton and Photon Radiation Therapy. | <b>Background:</b> Synchronous bilateral breast cancer (SBBC) is rare. The purpose of this study was to compare the dosimetric differences in intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT), helical tomotherapy (HT), and intensity-modulated proton therapy (IMPT) to find an optimal radiotherapy technique for bilateral breast cancer radiotherapy. <b>Methods:</b> For 11 patients who received synchronous bilateral whole-breast irradiation without local lymph nodal regions, six plans were designed for each patient: IMRT with a single isocenter (IMRT-ISO1), IMRT with two isocenters (IMRT-ISO2), VMAT with a single isocenter (VMAT-ISO1), VMAT with two isocenters (VMAT-ISO2), HT, and IMPT. The differences between the single- and dual-isocentric plans for IMRT and VMAT were compared, and the plan with the better quality was selected for further dosimetric comparisons with IMPT and HT. The plan aimed for a target coverage of at least 95% with the prescription dose of 50 Gy [relative biological effectiveness (RBE)] while minimizing the dose of organs at risk (OARs). <b>Results:</b> IMRT-ISO1 and VMAT-ISO2 plans were adopted for further dosimetric comparisons because of the reduced dose of the heart and/or lungs compared to IMRT-ISO2 and VMAT-ISO1 plans. The dose coverage of the planning target volume (PTV) was significantly higher in IMPT plans than that in all other plans. VMAT and IMPT plans showed the best conformity, whereas IMRT plans showed the worst conformity. Compared to IMRT and VMAT plans, IMPT and HT plans achieved significantly higher dose homogeneity. IMPT plans reduced the mean dose and low dose volume (V<sub>5</sub>, V<sub>10</sub>, and V<sub>20</sub>) of the heart, left anterior descending artery (LAD), and left ventricle (LV). In high-dose volumes of the heart and cardiac substructures, the IMPT, VMAT, and HT techniques showed similar advantages, and IMRT plans increased the values more than other techniques. IMPT plans had the maximal lung and normal tissue sparing but increased the skin dose compared to IMRT and VMAT plans. <b>Conclusions:</b> IMPT plans improve both the target coverage and the OARs sparing, especially for the heart, cardiac substructures (LAD and LV), lungs and normal tissue, in synchronous bilateral breast radiotherapy. VMAT and HT could be selected as suboptimal techniques for SBBC patients. |
2,328,076 | Tannic Acid Ameliorates STZ-Induced Alzheimer's Disease-Like Impairment of Memory, Neuroinflammation, Neuronal Death and Modulates Akt Expression. | Tannic acid (TA) is a hydrolysable glycosidic polyphenol polymer of gallic acid, which possesses neuroprotective properties. The aim of this study was to evaluate the effect of TA treatment on cognitive performance and neurochemical changes in an experimental model of sporadic dementia of Alzheimer's type (SDAT) induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) and to explore the potential cellular and molecular mechanisms underlying these effects. Adult male rats were divided into four groups: control, TA, STZ, and TA + STZ. Animals from TA and TA + STZ groups were treated with TA (30 mg/kg) daily, by gavage, for 21 days; others groups received water (1 mL/kg). Subsequently, an ICV injection of STZ (3 mg/kg) was administered into the lateral ventricles of animals from STZ and TA + STZ groups, while other groups received citrate buffer. Cognitive deficits (short-term memory), neuronal survival, neuroinflammation as well as expression of SNAP-25, Akt, and pAkt were evaluated in the cerebral cortex. TA treatment protected against the impairment of memory in STZ-induced SDAT. STZ promoted an increase in neuronal death and the levels of proinflammatory cytokines (IL-6 and TNF-α) and a decrease in Akt and pAkt expression; TA was able to restore these changes. Neither STZ nor TA altered SNAP-25 expression or the levels of IL-12 and IL-4 in the cerebral cortex. Our study highlights that treatment with TA prevents memory deficits and reestablishes Akt and pAkt expression, protecting against neuronal death and neuroinflammation in STZ-induced SDAT in rats. |
2,328,077 | Supraorbital Keyhole Approach for Resection of Prechiasmatic Craniopharyngioma: 2-Dimensional Operative Video. | Craniopharyngioma are benign extra-axial tumors occurring classically in the vicinity of the sella. Because of the complex anatomy surrounding the sella turcica comprising, among others, the vessels of the circle of Willis, the optic nerves, chiasma and optic pathway, the hypothalamus, the third ventricle, and the pituitary gland, a large variety of technical approaches have been described. We illustrate, in this video, a unilateral supraorbital keyhole approach to access and entirely extirpate a prechiasmatic craniopharyngioma.  A 40-yr-old healthy male presented to the emergency department with a history of rapid visual deterioration in the left eye in the last 10 d. A brain computed tomography scan showed a circumscribed prechiasmatic cystic lesion partially calcified that was radiologically compatible with a craniopharyngioma on the magnetic resonance imaging. We decided to access the lesion by a right-sided subfrontal corridor using a frontal wrinkle for the skin incision. This technique allows rapid and safe access to the central prechiasmatic region. By choosing a contralateral approach, we aim at optimizing the control on the opposite optic nerve with a perpendicular view. Total removal of the craniopharyngioma was accomplished without causing neurological deterioration. In fact, left eye visual disturbances were immediately retrieved after the surgery. No endocrinological issue or postoperative complication was reported. Minimal cosmetic disturbances are achieved with a meticulous skin incision and bone flap reconstruction. |
2,328,078 | CD8 T Cells and STAT1 Signaling Are Essential Codeterminants in Protection from Polyomavirus Encephalopathy. | JC polyomavirus (JCPyV), a human-specific virus, causes the aggressive brain-demyelinating disease progressive multifocal leukoencephalopathy (PML) in individuals with depressed immune status. The increasing incidence of PML in patients receiving immunotherapeutic and chemotherapeutic agents creates a pressing clinical need to define biomarkers to stratify PML risk and develop anti-JCPyV interventions. Mouse polyomavirus (MuPyV) CNS infection causes encephalopathology and may provide insight into JCPyV-PML pathogenesis. Type I, II, and III interferons (IFNs), which all signal via the STAT1 transcription factor, mediate innate and adaptive immune defense against a variety of viral infections. We previously reported that type I and II IFNs control MuPyV infection in non-central nervous system (CNS) organs, but their relative contributions to MuPyV control in the brain remain unknown. To this end, mice deficient in type I, II, or III IFN receptors or STAT1 were infected intracerebrally with MuPyV. We found that STAT1, but not type I, II, or III IFNs, mediated viral control during acute and persistent MuPyV encephalitis. Mice deficient in STAT1 also developed severe hydrocephalus, blood-brain barrier permeability, and increased brain infiltration by myeloid cells. CD8 T cell deficiency alone did not increase MuPyV infection and pathology in the brain. In the absence of STAT1 signaling, however, depletion of CD8 T cells resulted in lytic infection of the choroid plexus and ependymal lining, marked meningitis, and 100% mortality within 2 weeks postinfection. Collectively, these findings indicate that STAT1 signaling and CD8 T cells cocontribute to controlling MuPyV infection in the brain and CNS injury.<b>IMPORTANCE</b> A comprehensive understanding of JCPyV-induced PML pathogenesis is needed to define determinants that predispose patients to PML, a goal whose urgency is heightened by the lack of anti-JCPyV agents. A handicap to achieving this goal is the lack of a tractable animal model to study PML pathogenesis. Using intracerebral inoculation with MuPyV, we found that MuPyV encephalitis in wild-type mice causes an encephalopathy, which is markedly exacerbated in mice deficient in STAT1, a molecule involved in transducing signals from type I, II, and III IFN receptors. CD8 T cell deficiency compounded the severity of MuPyV neuropathology and resulted in dramatically elevated virus levels in the CNS. These findings demonstrate that STAT1 signaling and CD8 T cells concomitantly act to mitigate MuPyV-encephalopathy and control viral infection. |
2,328,079 | Intraventricular Ectopic Cerebellum. | Cerebellar ectopy is a rare finding, with few cases previously reported. Intraventricular localized cerebellar ectopy was described in only 1 case within the fourth ventricle.</AbstractText>A 9-year-old girl suffered for 2 years from bilateral frontoparietal headaches, sometimes accompanied by vomiting and photophobia. Magnetic resonance imaging demonstrated an oval-shaped lesion within the left lateral ventricle, characterized by well-defined margins without a clear cleavage plane from the adjacent choroid plexus. The mass presented an intermediate signal on T1- and T2-weighted sequences, similar to gray matter, and reduced ADC values on ADC maps compared with white matter, with no enhancement after gadolinium-based contrast injection. After resection, macroscopic examination revealed an organoid structure with leptomeningeal lining and a clear-cut cortex and white matter components. Histology demonstrated normal cerebellum with a double-layered cortex and normal underlying white matter. The cerebellar ectopy was focally covered by bundles of capillary vascular structures covered by a monostratified ependymal cell lining, consistent with choroid plexus.</AbstractText>We describe, for the first time to our knowledge, the case of a child with ectopic cerebellar tissue harboring the supratentorial ventricular system. Plausible etiologic mechanism consists in the herniation of the cerebellar germinal tissue into the ventricular system through the ependyma, allowing cell migration to the supratentorial compartment, followed by maturation into the normal cerebellum.</AbstractText>Copyright © 2020 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,080 | Cardioprotection in right heart failure. | Ischaemic and pharmacological conditioning of the left ventricle is mediated by the activation of signalling cascades, which finally converge at the mitochondria and reduce ischaemia/reperfusion (I/R) injury. Whereas the molecular mechanisms of conditioning in the left ventricle are well characterized, cardioprotection of the right ventricle is principally feasible but less established. Similar to what is known for the left ventricle, a dysregulation in signalling pathways seems to play a role in I/R injury of the healthy and failing right ventricle and in the ability/inability of the right ventricle to respond to a conditioning stimulus. The maintenance of mitochondrial function seems to be crucial in both ventricles to reduce I/R injury. As far as currently known, similar molecular mechanisms mediate ischaemic and pharmacological preconditioning in the left and right ventricles. However, the two ventricles seem to respond differently towards exercise-induced preconditioning. LINKED ARTICLES: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.23/issuetoc. |
2,328,081 | ETV for successful treatment of holocord syrinx with hydrocephalus: a case report. | to present evidence for the use of endoscopic third ventriculostomy (ETV) in the treatment of holocord syrinx.</AbstractText>ETV has been used in the treatment of obstructive hydrocephalus and syringomyelia secondary to Chiari 1 malformation. However, there have been no reports of ETV being utilised in the management of a holocord. We report a case of an 18 year old male with a symptomatic holocord syrinx who was successfully treated via ETV.</AbstractText>neurological improvement was noted both immediately and at follow up following ETV.</AbstractText>ETV may represent a viable treatment option for holocord syrinx in some population groups.</AbstractText> |
2,328,082 | Antioxidant-Conjugated Peptide Attenuated Metabolic Reprogramming in Pulmonary Hypertension. | Pulmonary arterial hypertension (PAH) is a chronic cardiopulmonary disorder instigated by pulmonary vascular cell proliferation. Activation of Akt was previously reported to promote vascular remodeling. Also, the irreversible nitration of Y350 residue in Akt results in its activation. NitroAkt was increased in PAH patients and the SU5416/Hypoxia (SU/Hx) PAH model. This study investigated whether the prevention of Akt nitration in PAH by Akt targeted nitroxide-conjugated peptide (NP) could reverse vascular remodeling and metabolic reprogramming. Treatment of the SU/Hx model with NP significantly decreased nitration of Akt in lungs, attenuated right ventricle (RV) hypertrophy, and reduced RV systolic pressure. In the PAH model, Akt-nitration induces glycolysis by activation of the glucose transporter Glut4 and lactate dehydrogenase-A (LDHA). Decreased G6PD and increased GSK3β in SU/Hx additionally shunted intracellular glucose via glycolysis. The increased glycolytic rate upregulated anaplerosis due to activation of pyruvate carboxylase in a nitroAkt-dependent manner. NP treatment resolved glycolytic switch and activated collateral pentose phosphate and glycogenesis pathways. Prevention of Akt-nitration significantly controlled pyruvate in oxidative phosphorylation by decreasing lactate and increasing pyruvate dehydrogenases activities. Histopathological studies showed significantly reduced pulmonary vascular proliferation. Based on our current observation, preventing Akt-nitration by using an Akt-targeted nitroxide-conjugated peptide could be a useful treatment option for controlling vascular proliferation in PAH. |
2,328,083 | Conservative treatment of caustic oesophageal injuries in children: 15 years of experience in a tertiary care paediatric centre. | Endoscopic dilatation is good choice of conservative treatment for caustic digestive tract injuries in children.</AbstractText>To set up a strategy of management of caustic digestive tract injury based on our experience and literature review.</AbstractText>We retrospectively analysed medical records of 34 paediatric patients who were admitted to the Centre of Paediatric Surgery of the Children's Hospital between 2000 and 2017. Age at presentation, gender, anatomic location, circumstances and distribution of injury, early and late complications, clinical signs, and the first aid were analysed. Upper gastrointestinal</i> (GI) endoscopy was performed within 12-24 h after ingestion in all cases. The Zargar classification system was used to grade the severity of the injury. Fisher's exact test was used for statistical analysis, with p</i> < 0.05 considered as the limit of statistical significance.</AbstractText>The upper GI endoscopy revealed caustic injuries in 5 (15%) and 8 (23%) patients were classified as grade IIa and IIb, respectively. Oesophageal and ventricle caustic injuries in 3 (9%) and 2 (6%) patients were classified as grade IIIa and IIIb, respectively. Thirteen patients with grade IIa and IIIb injuries suffered permanent damage and required repeated dilatation. All patients underwent stricture treatment using late or early endoscopic dilatation of the oesophagus. An average of 15 dilatation procedures were required to achieve a satisfactory lumen.</AbstractText>Our experience of 34 children revealed that endoscopic dilatation may be required as a primary treatment for oesophageal strictures.</AbstractText>Copyright: © 2019 Termedia Sp. z o. o.</CopyrightInformation> |
2,328,084 | 3D Anatomy of the Developing Heart: Understanding Ventricular Septation. | Understanding how the four-chambered mammalian heart is formed from a simple, looped tube remains challenging, notwithstanding the descriptive accounts left by generations of cardiac anatomists. Much of the difficulty lies in attempting to visualize an intricate series of morphological transformations through the restrictive lens of two-dimensional images derived from histology. Modern imaging methods offer a way to overcome this limitation by providing comprehensive and high-resolution image sets of the developing heart. We have used one such method, high-resolution episcopic microscopy (HREM), to obtain virtual three-dimensional (3D) models of successive stages in mouse heart development. Taking advantage of the ability afforded by 3D modeling to view each heart in any orientation or erosion plane, we provide an illustrated account of how the mouse heart divides into left and right ventricular chambers, and how each acquires its own distinct outflow vessel. |
2,328,085 | Persistent Cyfip1 Expression Is Required to Maintain the Adult Subventricular Zone Neurogenic Niche. | Neural stem cells (NSCs) persist throughout life in the subventricular zone (SVZ) neurogenic niche of the lateral ventricles as Type B1 cells in adult mice. Maintaining this population of NSCs depends on the balance between quiescence and self-renewing or self-depleting cell divisions. Interactions between B1 cells and the surrounding niche are important in regulating this balance, but the mechanisms governing these processes have not been fully elucidated. The cytoplasmic FMRP-interacting protein (Cyfip1) regulates apical-basal polarity in the embryonic brain. Loss of Cyfip1 during embryonic development in mice disrupts the embryonic niche and affects cortical neurogenesis. However, a direct role for Cyfip1 in the regulation of adult NSCs has not been established. Here, we demonstrate that Cyfip1 expression is preferentially localized to B1 cells in the adult mouse SVZ. Loss of <i>Cyfip1</i> in the embryonic mouse brain results in altered adult SVZ architecture and expansion of the adult B1 cell population at the ventricular surface. Furthermore, acute deletion of <i>Cyfip1</i> in adult NSCs results in a rapid change in adherens junction proteins as well as increased proliferation and number of B1 cells at the ventricular surface. Together, these data indicate that Cyfip1 plays a critical role in the formation and maintenance of the adult SVZ niche; furthermore, deletion of <i>Cyfip1</i> unleashes the capacity of adult B1 cells for symmetric renewal to increase the adult NSC pool.<b>SIGNIFICANCE STATEMENT</b> Neural stem cells (NSCs) persist in the subventricular zone of the lateral ventricles in adult mammals, and the size of this population is determined by the balance between quiescence and self-depleting or renewing cell division. The mechanisms regulating these processes are not fully understood. This study establishes that the cytoplasmic FMRP interacting protein 1 (Cyfip1) regulates NSC fate decisions in the adult subventricular zone and adult NSCs that are quiescent or typically undergo self-depleting divisions retain the ability to self-renew. These results contribute to our understanding of how adult NSCs are regulated throughout life and has potential implications for human brain disorders. |
2,328,086 | Resuscitating the Chimney Graft to Innominate Artery for Straightforward Cannulation During Infancy. | Arterial cannulation with a chimney polytetrafluoroethylene graft to the innominate artery is commonly used for antegrade cerebral perfusion during neonatal aortic arch surgery. When properly retained and prepared before sternal closure, resuscitation of the polytetrafluoroethylene graft to innominate artery can be performed months later during sternal reentry. It is a safe and reproducible technique for expeditious arterial cannulation at stage II palliation in single-ventricle patients or complete intracardiac repair of biventricular lesions. We report our experience utilizing this technique successfully during reoperation in 90 of 92 patients, with no adverse thromboembolic events identified. |
2,328,087 | Targeting Tanycytes: Balance between Efficiency and Specificity. | Tanycytes are peculiar ependymoglial cells lining the bottom and the lateral wall of the third ventricle. For a decade, the utilization of molecular genetic approaches allowed us to make important discoveries about their diverse physiological functions. Here, I review the current methods used to target tanycytes, focusing on their specificity, their efficiency, their limitations, as well as their potential future improvements. |
2,328,088 | A Rare Case of Intracranial Nongerminomatous Germ Cell Tumor in a 21-Year-Old Romanian Male. | Extragonadal germ cell tumors are a rare entity that is more prevalent in infants and young children, with preference to midline structures. The category of intracranial germ cell tumors is divided into pure germ cell tumors (GCTs) versus nongerminomatous germ cell tumors (NGGCTs). They are usually present in the second decade of life with a male preponderance. We present here a rare case of intracranial NGGCT in a 21-year-old Romanian male, who presented with complaints of emesis, ataxic gait, and diplopia. A computed tomography scan of the head in the emergency department revealed a pineal/suprapineal mass along with obstructive hydrocephalus and dilated lateral and third ventricles without any bleeding. MRI of the cervical, thoracic, and lumbar spine showed no evidence of leptomeningeal metastasis. The patient had elevated serum markers of beta-hCG and AFP, which pointed towards a diagnosis of nongerm cell tumor, as in pure GCTs, these markers are normal. To relieve the obstruction from the mass effect, the patient had an endoscopic third ventriculostomy (EVT). However, after the procedure, he developed central diabetes insipidus as a complication with a triphasic response. Biopsy of the mass revealed atypical cells with granular architecture and atypical glands with positive immune histological markers for NGGCT. These findings supported the diagnosis of mixed germ cell tumor with yolk sac carcinoma and seminoma components. Patient's transient central diabetes resolved with normalization in his urine output. He was eventually stabilized and returned to Romania for further management. In summary, intracranial germ cell tumors are rare brain tumors that should be distinguished based on histology and tumor markers as they will help in the guidance of therapy. An initial evaluation with neuroimaging, tumor markers, cytology from CSF, and biopsy is a must to distinguish further treatment and prognosis. |
2,328,089 | Changed PGA and POSTN levels in choroid plexus are associated with depressive-like behaviors in mice. | Major depressive disorder (MDD) has become a potential cause of death and disability among young people worldwide. Numerous studies have indicated that the different cerebrospinal fluid (CSF) proteins may be used as mediums for MDD. Given the emergent interest of CSF proteins in MDD, we validated proteins expression in the choroid plexus (CP), the brain region that produces CSF in the lateral ventricle, the third ventricle, and the fourth ventricle of the central nervous system (CNS). The CSF constantly exchanges molecular substances with the brain tissue, which can dynamically reflect the metabolic microenvironment of the brain. In our previous study, Pepsin A (PGA) and periostin (POSTN) was associated with depressive-like behaviors of depressed macaca fascicularis models in CSF. Moreover, proteins that are expressed in the CP can be secreted into the CSF and may be associated MDD. This study sought to demonstrate the discrepancy of PGA and POSTN in the CP between Lipopolysaccharide (LPS)-induce depressed mice models and wild type (WT) mice. Our findings suggest that PGA and POSTN expression in CP of mice could be a possible candidate pathogenesis involved in MDD, which may contribute to a better understanding and treatment of MDD. |
2,328,090 | Anatomical and Functional Characterization in Children With Unilateral Cerebral Palsy: An Atlas-Based Analysis. | <i>Background</i>. Variability in hand function among children with unilateral cerebral palsy (UCP) might reflect the type of brain injury and resulting anatomical sequelae. <i>Objective</i>. We used atlas-based analysis of structural images to determine whether children with periventricular (PV) versus middle cerebral artery (MCA) injuries might exhibit unique anatomical characteristics that account for differences in hand function. <i>Methods</i>. Forty children with UCP underwent structural brain imaging using 3-T magnetic resonance imaging. Brain lesions were classified as PV or MCA. A group of 40 typically developing (TD) children served as comparison controls. Whole brains were parcellated into 198 structures (regions of interest) to obtain volume estimates. Dexterity and bimanual hand function were assessed. Unbiased, differential expression analysis was performed to determine volumetric differences between PV and MCA groups. Principal component analysis (PCA) was performed and the top 3 components were extracted to perform regression on hand function. <i>Results</i>. Children with PV had significantly better hand function than children with MCA. Multidimensional scaling analysis of volumetric data revealed separate clustering of children with MCA, PV, and TD children. PCA extracted anatomical components that comprised the 2 types of brain injury. In the MCA group, reductions of volume were concentrated in sensorimotor structures of the injured hemisphere. Models using PCA predicted hand function with greater accuracy than models based on qualitative brain injury type. <i>Conclusions</i>. Our results highlight unique quantitative differences in children with UCP that also predict differences in hand function. The systematic discrimination between groups found in our study reveals future questions about the potential prognostic utility of this approach. |
2,328,091 | Is the anatomical distribution of low-grade gliomas linked to regions of gliogenesis? | According to the stem cell theory, two neurogenic niches in the adult human brain may harbor cells that initiate the formation of gliomas: The larger subventricular zone (SVZ) and the subgranular zone (SGZ) in the hippocampus. We wanted to explore whether defining molecular markers in low-grade gliomas (LGG; WHO grade II) are related to distance to the neurogenic niches.</AbstractText>Patients treated at two Norwegian university hospitals with population-based referral were included. Eligible patients had histopathological verified supratentorial low-grade glioma. IDH mutational status and 1p19q co-deletion status was retrospectively assessed. 159 patients were included, and semi-automatic tumor segmentation was done from pre-treatment T2-weighted (T2W) or Fluid-Attenuated Inversion Recovery (FLAIR) images. 3D maps showing the anatomical distribution of the tumors were then created for each of the three molecular subtypes (IDH mutated/1p19q co-deleted, IDH mutated and IDH wild-type). Both distance from tumor center and tumor border to the neurogenic niches were recorded.</AbstractText>In this population-based cohort of previously untreated low-grade gliomas, we found that low-grade gliomas are more often found closer to the SVZ than the SGZ, but IDH wild-type tumors are more often found near SGZ.</AbstractText>Our study suggests that the stem cell origin of IDH wild-type and IDH mutated low-grade gliomas may be different.</AbstractText> |
2,328,092 | Infantile atypical subependymal giant cell astrocytoma. | Subependymal giant cell astrocytoma is a benign WHO grade I intraventricular tumor arise in patients with tuberous sclerosis complex. Previous reported described histopathological predictors of more aggressive forms, terms atypical SEGA in infantile age group. Other reports showed possible transformation of SEGA into glioblastoma, or misdiagnosis as glioblastoma due to the presence of atypical histopathological features. Here, we report a case of an infant who presented with right frontal extraventricular SEGA and underwent craniotomy with complete resection. Eight months later, he presented with fast recurrence in same location with midline shift and subfalcine herniation. Histopathological description showed high grade features including Ki labeling index of 60%, atypical mitotic figures, cellular plemorphism and necrosis. We also discussed the possible presence of different entity (termed atypical SEGA) which may have more aggressive clinical course, with literature review of predictors of SEGA aggressiveness and possible transformation/misdiagnosis as glioblastoma. |
2,328,093 | MicroRNA-152 attenuates neuroinflammation in intracerebral hemorrhage by inhibiting thioredoxin interacting protein (TXNIP)-mediated NLRP3 inflammasome activation. | Neuroinflammation significantly contributes to brain injury and neurological deterioration following intracerebral hemorrhage (ICH). MicroRNA-152(miR-152) was reported to be downregulated in ICH patients and to possess anti-inflammatory properties in other diseases. In this study, we aimed to explore the role of miR-152 in ICH, and the underlying mechanisms, using a collagenase-induced rat ICH model and hemin-exposure as a cell model. We first confirmed that miR-152 was consistently downregulated in both models. Overexpression of miR-152 in microglial BV2 cells reduced hemin-induced inflammatory response and reactive oxygen species (ROS) generation, thus protecting co-cultured neuronal HT22 cells. Moreover, overexpression of miR-152 by intracerebroventricular lentivirus injection in ICH rats significantly alleviated neurodecifits, brain edema, and hematoma. These changes were associated with a marked reduction in ICH-induced neuronal death, as detected by co-staining of NeuN and TUNEL, and ICH-induced neuroinflammation, as revealed by inflammatory cytokine levels as well as by the number of Iba1 positive-stained cells in the perihematomal region. Mechanistically, miR-152 significantly inhibited ICH-induced TXNIP expression, and its overexpression blocked the interaction between TXNIP and NOD-like receptor pyrin domain containing 3(NLRP3), thus inhibiting NLRP3-driven inflammasome activation to attenuate neuroinflammation in vivo and in vitro. Moreover, the results of si-TXNIP transfection further confirmed that TXNIP inhibition was involved in the reduction of NLRP3 inflammasome activation by the overexpression of miR-152. Collectively, the present study demonstrates that miR-152 confers protection against ICH-induced neuroinflammation and brain injury by inhibiting TXNIP-mediated NLRP3 inflammasome activation, indicating a potential strategy for ICH treatment. |
2,328,094 | NF-RCNN: Heart localization and right ventricle wall motion abnormality detection in cardiac MRI. | Convolutional neural networks (CNNs) are extensively used in cardiac image analysis. However, heart localization has become a prerequisite to these networks since it decreases the size of input images. Accordingly, recent CNNs benefit from deeper architectures in gaining abstract semantic information. In the present study, a deep learning-based method was developed for heart localization in cardiac MR images. Further, Network in Network (NIN) was used as the region proposal network (RPN) of the faster R-CNN, and then NIN Faster-RCNN (NF-RCNN) was proposed. NIN architecture is formed based on "MLPCONV" layer, a combination of convolutional network and multilayer perceptron (MLP). Therefore, it could deal with the complicated structures of MR images. Furthermore, two sets of cardiac MRI dataset were used to evaluate the network, and all the evaluation metrics indicated an absolute superiority of the proposed network over all related networks. In addition, FROC curve, precision-recall (PR) analysis, and mean localization error were employed to evaluate the proposed network. In brief, the results included an AUC value of 0.98 for FROC curve, a mean average precision of 0.96 for precision-recall curve, and a mean localization error of 6.17 mm. Moreover, a deep learning-based approach for the right ventricle wall motion analysis (WMA) was performed on the first dataset and the effect of the heart localization on this algorithm was studied. The results revealed that NF-RCNN increased the speed and decreased the required memory significantly. |
2,328,095 | Third Ventricular Injection of CCL2 in Rat Embryo Stimulates CCL2/CCR2 Neuroimmune System in Neuroepithelial Radial Glia Progenitor Cells: Relation to Sexually Dimorphic, Stimulatory Effects on Peptide Neurons in Lateral Hypothalamus. | Clinical and animal studies show maternal alcohol consumption during pregnancy causes in offspring persistent alterations in neuroimmune and neurochemical systems known to increase alcohol drinking and related behaviors. Studies in lateral hypothalamus (LH) demonstrate in adolescent offspring that maternal oral administration of ethanol stimulates the neuropeptide, melanin-concentrating hormone (MCH), together with the inflammatory chemokine C-C motif ligand 2 (CCL2) and its receptor CCR2 which are increased in most MCH neurons. These effects, consistently stronger in females than males, are detected in embryos, not only in LH but hypothalamic neuroepithelium (NEP) along the third ventricle where neurons are born and CCL2 is stimulated within radial glia progenitor cells and their laterally projecting processes that facilitate MCH neuronal migration toward LH. With ethanol's effects similarly produced by maternal peripheral CCL2 administration and blocked by CCR2 antagonist, we tested here using in utero intracerebroventricular (ICV) injections whether CCL2 acts locally within the embryonic NEP. After ICV injection of CCL2 (0.1 µg/µl) on embryonic day 14 (E14) when neurogenesis peaks, we observed in embryos just before birth (E19) a significant increase in endogenous CCL2 within radial glia cells and their processes in NEP. These auto-regulatory effects, evident only in female embryos, were accompanied by increased density of CCL2 and MCH neurons in LH, more strongly in females than males. These results support involvement of embryonic CCL2/CCR2 neuroimmune system in radial glia progenitor cells in mediating sexually dimorphic effects of maternal challenges such as ethanol on LH MCH neurons that colocalize CCL2 and CCR2. |
2,328,096 | Site-specific acetyl-mimetic modification of cardiac troponin I modulates myofilament relaxation and calcium sensitivity. | Cardiac troponin I (cTnI) is an essential physiological and pathological regulator of cardiac relaxation. Significant to this regulation, the post-translational modification of cTnI through phosphorylation functions as a key mechanism to accelerate myofibril relaxation. Similar to phosphorylation, post-translational modification by acetylation alters amino acid charge and protein function. Recent studies have demonstrated that the acetylation of cardiac myofibril proteins accelerates relaxation and that cTnI is acetylated in the heart. These findings highlight the potential significance of myofilament acetylation; however, it is not known if site-specific acetylation of cTnI can lead to changes in myofilament, myofibril, and/or cellular mechanics. The objective of this study was to determine the effects of mimicking acetylation at a single site of cTnI (lysine-132; K132) on myofilament, myofibril, and cellular mechanics and elucidate its influence on molecular function.</AbstractText>To determine if pseudo-acetylation of cTnI at 132 modulates thin filament regulation of the acto-myosin interaction, we reconstituted thin filaments containing WT or K132Q (to mimic acetylation) cTnI and assessed in vitro motility. To test if mimicking acetylation at K132 alters cellular relaxation, adult rat ventricular cardiomyocytes were infected with adenoviral constructs expressing either cTnI K132Q or K132 replaced with arginine (K132R; to prevent acetylation) and cell shortening and isolated myofibril mechanics were measured. Finally, to confirm that changes in cell shortening and myofibril mechanics were directly due to pseudo-acetylation of cTnI at K132, we exchanged troponin containing WT or K132Q cTnI into isolated myofibrils and measured myofibril mechanical properties.</AbstractText>Reconstituted thin filaments containing K132Q cTnI exhibited decreased calcium sensitivity compared to thin filaments reconstituted with WT cTnI. Cardiomyocytes expressing K132Q cTnI had faster relengthening and myofibrils isolated from these cells had faster relaxation along with decreased calcium sensitivity compared to cardiomyocytes expressing WT or K132R cTnI. Myofibrils exchanged with K132Q cTnI ex vivo demonstrated faster relaxation and decreased calcium sensitivity.</AbstractText>Our results indicate for the first time that mimicking acetylation of a specific cTnI lysine accelerates myofilament, myofibril, and myocyte relaxation. This work underscores the importance of understanding how acetylation of specific sarcomeric proteins affects cardiac homeostasis and disease and suggests that modulation of myofilament lysine acetylation may represent a novel therapeutic target to alter cardiac relaxation.</AbstractText>Copyright © 2020 Elsevier Ltd. All rights reserved.</CopyrightInformation> |
2,328,097 | (-)-Epicatechin Reduces the Blood Pressure of Young Borderline Hypertensive Rats During the Post-Treatment Period. | This study investigated the effects of (-)-epicatechin (Epi) in young male borderline hypertensive rats (BHR) during two weeks of treatment (Epi group, 100 mg/kg/day p.o.) and two weeks post treatment (PE group). Epi reduced blood pressure (BP), which persisted for two weeks post treatment. This was associated with delayed reduction of anxiety-like behaviour. Epi significantly increased nitric oxide synthase (NOS) activities in the aorta and left heart ventricle (LHV) vs. the age-matched controls without affecting the brainstem and frontal neocortex. Furthermore, Epi significantly reduced the superoxide production in the aorta and relative content of iron-containing compounds in blood. Two weeks post treatment, the NOS activities and superoxide productions in the heart and aorta did not differ from the age-matched controls. The gene expressions of the NOSs (<i>nNO</i>S, <i>iNOS</i><i>,</i> <i>eNOS</i>), nuclear factor erythroid 2-related factor 2 (<i>Nrf2</i>), and peroxisome proliferator-activated receptor-γ (<i>PPAR</i>-γ) remained unaltered in the aorta and LHV of the Epi and PE groups. In conclusion, while Epi-induced a decrease of the rats' BP persisted for two weeks post treatment, continuous Epi treatments seem to be necessary for maintaining elevated NO production as well as redox balance in the heart and aorta without changes in the <i>NOSs</i>, <i>Nrf2</i>, and <i>PPAR</i>-γ gene expressions. |
2,328,098 | The effect of Gamma Knife radiosurgery on large posterior fossa metastases and the associated mass effect from peritumoral edema. | Gamma Knife radiosurgery (GKRS) as monotherapy is an option for the treatment of large (≥ 2 cm) posterior fossa brain metastases (LPFMs). However, there is concern regarding possible posttreatment increase in peritumoral edema (PTE) and associated compression of the fourth ventricle. This study evaluated the effects and safety of GKRS on tumor and PTE control in LPFM.</AbstractText>The authors performed a single-center retrospective review of 49 patients with 51 LPFMs treated with GKRS. Patients with at least 1 clinical and radiological follow-up visit were included. Tumor, PTE, and fourth ventricle volumetric measurements were used to assess efficacy and safety. Overall survival was a secondary outcome.</AbstractText>Fifty-one lesions in 49 consecutive patients were identified; 57.1% of patients were male. At the time of GKRS, the median age was 61.5 years, and the median Karnofsky Performance Status score was 90. The median number of LPFMs and overall brain metastases were 1 and 2, respectively. The median overall tumor, PTE, and fourth ventricle volumes at diagnosis were 4.96 cm3 (range 1.4-21.1 cm3), 14.98 cm3 (range 0.6-71.8 cm3), and 1.23 cm3 (range 0.3-3.2 cm3), respectively, and the median lesion diameter was 2.6 cm (range 2.0-5.07 cm). The median follow-up time was 7.3 months (range 1.6-57.2 months). At the first follow-up, 2 months posttreatment, the median tumor volume decreased by 58.66% (range -96.95% to +48.69%, p < 0.001), median PTE decreased by 78.10% (range -99.92% to +198.35%, p < 0.001), and the fourth ventricle increased by 24.97% (range -37.96% to +545.6%, p < 0.001). The local control rate at first follow-up was 98.1%. The median OS was 8.36 months. No patient required surgical intervention, external ventricular drainage, or shunting between treatment and first follow-up. However, 1 patient required a ventriculoperitoneal shunt at 23 months from treatment. Posttreatment, 65.30% received our general steroid taper, 6.12% received no steroids, and 28.58% required prolonged steroid treatment.</AbstractText>In this retrospective analysis, patients with LPFMs treated with GKRS had a statistically significant posttreatment reduction in tumor size and PTE and marked opening of the fourth ventricle (all p < 0.001). This study demonstrates that GKRS is well tolerated and can be considered in the management of select cases of LPFMs, especially in patients who are poor surgical candidates.</AbstractText> |
2,328,099 | Human fetal mesoangioblasts reveal tissue-dependent transcriptional signatures. | Mesoangioblasts (MABs) derived from adult skeletal muscles are well-studied adult stem/progenitor cells that already entered clinical trials for muscle regeneration in genetic diseases; however, the transcriptional identity of human fetal MABs (fMABs) remains largely unknown. Herein we analyzed the transcriptome of MABs isolated according to canonical markers from fetal atrium, ventricle, aorta, and skeletal muscles (from 9.5 to 13 weeks of age) to uncover specific gene signatures correlating with their peculiar myogenic differentiation properties inherent to their tissue of origin. RNA-seq analysis revealed for the first time that human MABs from fetal aorta, cardiac (atrial and ventricular), and skeletal muscles display subsets of differentially expressed genes likely representing distinct expression signatures indicative of their original tissue. Identified GO biological processes and KEGG pathways likely account for their distinct differentiation outcomes and provide a set of critical genes possibly predicting future specific differentiation outcomes. This study reveals novel information regarding the potential of human fMABs that may help to improve specific differentiation outcomes relevant for therapeutic muscle regeneration. |
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