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2,328,800 | Early Prediction of Periventricular Leukomalacia Using Quantitative Texture Analysis of Serial Cranial Ultrasound Scans in Very Preterm Infants. | We compared texture parameters of serial cranial ultrasound (cUS) images of periventricular leukomalacia (PVL) and normal periventricular echogenicity (PVE) in very preterm infants and evaluated the early predictive values of texture analysis (TA) for PVL. Ten individuals with PVL and 10 control individuals with PVE assessed with an initial cUS within 1 wk of birth and follow-up cUS at 2-3 and 4-6 wk of life were included. TA was performed on the region of interest of PVE at the parieto-occipital area on serial cUS. Opposite changes in variance were obtained between the first two cUS sessions in both groups (p = 0.017 in PVL and p = 0.005 in PVE). The variance-to-mean ratio (VMR) between the second and first cUS sessions differed (p = 0.016) and reliably stratified the groups (area under the receiver operating characteristic curve: 0.820, 95% confidence interval: 0.587-1.000, sensitivity: 100%, specificity: 60%). TA of serial cUS helps to predict PVL within 3 wk of life. |
2,328,801 | Spontaneous Tumor Regression of Intracranial Solitary Fibrous Tumor Originating From the Medulla Oblongata: A Case Report and Literature Review. | Intracranial solitary fibrous tumor (SFT) is a rare occurrence and involvement of the fourth ventricle rarely reported. Because of its rarity, some characteristics of intracranial SFT seem to still remain uncertain.</AbstractText>This study describes a very rare case of intracranial SFT in a 55-year-old woman who presented with gait disturbance and numbness in bilateral upper limbs from 3 months before visiting the hospital. Head magnetic resonance imaging scan revealed a homogeneously enhancing mass lesion located primarily in the fourth ventricle extending into the spinal canal and left foramen of Luschka, with a maximum diameter of 60 mm. Notably, this tumor presented spontaneous partial regression during waiting planned surgery without therapy, including chemotherapy and radiotherapy. This patient underwent a midline suboccipital craniotomy and resection of the tumor. Interestingly, there was no attachment to the dura mater of the posterior cranial fossa and the lesion was only attached to the dorsal part of the medulla oblongata.</AbstractText>Although the location of the SFT in the fourth ventricle is rare, SFT should be considered as 1 of the differential diagnosis of fourth ventricle tumors. In addition, this case indicates that SFT in the fourth ventricle may regress on occasion spontaneously without a precisely known cause for this spontaneous partial regression.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,802 | Disproportionately large communicating fourth ventricle: two case reports. | Management of the disproportionately large communicating fourth ventricle is still problematic.</AbstractText>Two cases of disproportionately large communicating fourth ventricle were treated successfully. One was a case of a 51-year-old Han Chinese woman with a complaint of headache and dizziness of 1 year's duration. Magnetic resonance imaging (MRI) demonstrated hydrocephalus with a disproportionately large fourth ventricle. She underwent a ventriculo-peritoneal shunt of the right lateral ventricle. Her symptoms were relieved totally. Five years later, magnetic resonance imaging showed she had a normal ventricular system. The other case was a 24-year-old Han Chinese man with a 2-month history of headache and dizziness accompanied by progressive loss of bilateral vision. Magnetic resonance imaging revealed hydrocephalus with a disproportionately large fourth ventricle, crowded posterior cranial fossa, and syringomyelia extending from C1 to C5. He underwent suboccipital and C1 decompression and duraplasty. Shortly after the surgery, his symptoms were relieved completely, the syringomyelia completely disappeared, and the fourth ventricle became significantly smaller.</AbstractText>The management of the disproportionately large communicating fourth ventricle should be individualized. If it coexists with crowded posterior cranial fossa or syringomyelia, posterior fossa decompression could be an option for initial management. If there is no sign of crowded posterior cranial fossa or syringomyelia, shunt of the lateral ventricles might be the first choice.</AbstractText> |
2,328,803 | Clinical outcomes after implantation of quadripolar compared to bipolar left ventricular leads in patients undergoing cardiac resynchronization therapy: a systematic review and meta-analysis. | Some retrospective and prospective studies in heart failure patients with indication for cardiac resynchronization therapy (CRT) suggest better clinical outcomes for quadripolar (QP) left ventricular (LV) leads over bipolar (BP) leads. Although, lead failure remains an important safety concern, when using these more complex, novel electrodes. To evaluate safety and efficacy outcomes for QP vs. BP LV leads in patients receiving CRT.</AbstractText>We performed a comprehensive literature search through 2018 in PubMed, Cochrane Library, and Google Scholar databases to identify studies comparing patients with QP and BP LV CRT leads. A total of 12 studies were selected for analysis comprising 31 403 patients (QP lead: 22 429 patients; BP lead: 8974 patients). Eight studies examined the effects of CRT on survival. In these studies, use of QP electrodes was associated with significantly better survival compared to patients with BP LV leads (OR 0.61, 95% CI 0.50-0.76; P < 0.01). Clinical improval measured in New York Heart Association functional class (OR 0.59, 95% CI 0.34-1.01; P = 0.05) and hospitalization rates (OR 0.67, 95% CI 0.55-0.83; P < 0.01) were also improved in patients receiving QP leads. Lead malfunctions defined as LV lead failure resulting in lead deactivation (OR 0.57, 95% CI 0.34-0.98; P = 0.04) or LV lead dislodgement requiring LV lead replacement/repositioning (OR 0.48; 95% CI 0.31-0.75; P < 0.01) were more often encountered among patients with BP leads compared to patients with QP leads.</AbstractText>Our meta-analysis suggests distinct benefits of QP over BP electrodes in patients undergoing CRT.</AbstractText>Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.</CopyrightInformation> |
2,328,804 | Thalamic volume loss as an early sign of amnestic mild cognitive impairment. | The aim of this study was to compare brain volume reduction in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) with age-related changes in age- and gender-matched healthy individuals. Sixty-six patients were divided in three groups based on medical history, neurological and neurocognitive assessment: 26 patients with AD, 20 patients with aMCI and 20 healthy controls. All participants underwent high-resolution magnetic resonance (MR) imaging on 3 T unit. MR volumetry of cerebral cortex, white matter and lateral ventricles volumes, as well as volumes of subcortical nuclei (hippocampus, amygdala, thalamus) was performed. Global cerebral and grey matter volumes were lower in AD patients compared to aMCI (p = 0.023 and p = 0.001, respectively) and controls (p < 0.001 and p < 0.001, respectively). Volume of lateral ventricles was significantly higher in AD patients compared to controls (right p = 0.007, left p = 0.007). Volumes of thalamus were lower in AD patients (right p < 0.001, left p < 0.001), and in aMCI patients (right p = 0.004, left p = 0.015), compared to controls. Hippocampal volume was lower in AD patients compared to both aMCI patients (right p = 0.047, left p = 0.003) and controls (right p < 0.001, left p < 0.001). In aMCI patients, hippocampal volume was lower than in controls (right p = 0.004, left p = 0.007). Volumes of amygdala were lower in AD patients compared to controls (righ p = 0.003, left p = 0.001). Our results show that thalamic volume loss could be an early sign associated with poorercognitiveperformance in aMCI, preceeding the atrophy of amygdala, global grey and white matter volume loss, and cerebrospinal fluid spaces dilatation. |
2,328,805 | Preterm brain injury: Germinal matrix-intraventricular hemorrhage and post-hemorrhagic ventricular dilatation. | Germinal matrix hemorrhage and intraventricular hemorrhages (GMH-IVH) remain a common and clinically significant problem in preterm infants, particularly extremely preterm infants. A large GMH-IVH is often complicated by posthemorrhagic ventricular dilation (PHVD) or parenchymal hemorrhagic infarction and is associated with an increased risk of adverse neurologic sequelae. The widespread use of cranial ultrasonography since the early 1980s has shown a gradual decrease in the incidence of GMH-IVH and has helped with the identification of antenatal and perinatal risk factors and timing of the lesion. The increased use of magnetic resonance imaging (MRI) has contributed to more detailed visualization of the site and extent of the GMH-IVH. In addition, MRI has contributed to the awareness of associated white matter changes as well as associated cerebellar hemorrhages. Although GMH-IVH and PHVD still cannot be prevented, cerebrospinal fluid drainage initiated in the early stage of PHVD development seems to be associated with a better neurodevelopmental outcome. Further studies are underway to improve treatment strategies for PHVD and to potentially prevent and repair GMH-IVH and PHVD and associated brain injury. This chapter discusses the pathogenesis, incidence, risk factors, and management, including preventive measures, of GHM-IVH and PHVD. |
2,328,806 | Extubation on the operating table in patients with right ventricular pressure overload undergoing biventricular repair†.<Pagination><StartPage>904</StartPage><EndPage>910</EndPage><MedlinePgn>904-910</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1093/ejcts/ezz139</ELocationID><Abstract><AbstractText Label="OBJECTIVES" NlmCategory="OBJECTIVE">Right ventricular pressure overload, which can result in restrictive right ventricular physiology, predicts slow recovery after biventricular repair of congenital heart defects. The goal of the study was to assess how extubation in the operating room influences the postoperative course in these patients.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">Between January 2013 and June 2017, a total of 65 children [median age 0.96 (0.13-9.47) years; median weight 8 (3.05-25.8) kg] with right ventricular pressure overload underwent an intracardiac correction. The most common malformations were tetralogy of Fallot (n = 34) and double outlet right ventricle with pulmonary stenosis (n = 11). The patients were divided into 2 groups: the first (n = 36) comprised late extubated (LE) and the second (n = 29), early extubated (EE) children, immediately after chest closure in the operating room. Preoperative, perioperative and postoperative records were analysed retrospectively.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Children who had EE had a lower heart rate (EE 124.2 vs LE 133.6 bpm; P = 0.03), higher arterial blood pressure (systolic: EE 87.9 ± 9.35 vs LE 81.4 ± 12.0 mmHg; P = 0.029; diastolic: EE 51.1 ± 6.5 vs LE 45.9 ± 6.64 mmHg; P = 0.003), lower central venous pressure (EE 8.6 ± 1.89 mmHg vs LE 9.9 ± 2.42 mmHg; P = 0.03), fewer pleural effusions in the first 6 postoperative days (EE 1.38 ml/kg/day vs LE 5.98 ml/kg/day; P = 0.009), shorter time of dopamine support ≥3 μg/kg (EE 7.29 ± 12.26 h vs LE 34.78 ± 38.05 h, P < 0.001), shorter stays in the intensive care unit (EE 2.7 ± 2.67 vs LE 5.0 ± 4.77 days, P = 0.001) and hospital (EE 11.8 ± 4.79 vs LE 15.5 ± 7.8 days; P = 0.022).</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Extubation in the operating room of children with right ventricular pressure overload undergoing biventricular correction is feasible and safe and has a beneficial effect on the postoperative course.</AbstractText><CopyrightInformation>© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Nawrocki</LastName><ForeName>Pawel</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Division of Pediatric Cardiac Surgery, Department of Cardiothoracic Surgery, University Hospital Münster, Münster, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wisniewski</LastName><ForeName>Konrad</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Division of Pediatric Cardiac Surgery, Department of Cardiothoracic Surgery, University Hospital Münster, Münster, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Schmidt</LastName><ForeName>Christoph</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bruenen</LastName><ForeName>Andreas</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Debus</LastName><ForeName>Volker</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Department of Pediatric Cardiology, University Hospital Münster, Münster, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Malec</LastName><ForeName>Edward</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Division of Pediatric Cardiac Surgery, Department of Cardiothoracic Surgery, University Hospital Münster, Münster, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Januszewska</LastName><ForeName>Katarzyna</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Division of Pediatric Cardiac Surgery, Department of Cardiothoracic Surgery, University Hospital Münster, Münster, Germany.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Germany</Country><MedlineTA>Eur J Cardiothorac Surg</MedlineTA><NlmUniqueID>8804069</NlmUniqueID><ISSNLinking>1010-7940</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D060666" MajorTopicYN="Y">Airway Extubation</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000379" MajorTopicYN="N">methods</QualifierName><QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName><QualifierName UI="Q000706" MajorTopicYN="N">statistics & numerical data</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001794" MajorTopicYN="N">Blood Pressure</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002648" MajorTopicYN="N">Child</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002675" MajorTopicYN="N">Child, Preschool</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006330" MajorTopicYN="N">Heart Defects, Congenital</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006339" MajorTopicYN="N">Heart Rate</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006352" MajorTopicYN="Y">Heart Ventricles</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007223" MajorTopicYN="N">Infant</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018497" MajorTopicYN="Y">Ventricular Dysfunction, Right</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017725" MajorTopicYN="N">Ventricular Pressure</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Biventricular repair</Keyword><Keyword MajorTopicYN="N">Extubation in the operating room</Keyword><Keyword MajorTopicYN="N">Restrictive right ventricular physiology</Keyword><Keyword MajorTopicYN="N">Right ventricular pressure overload</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>11</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2019</Year><Month>3</Month><Day>10</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>3</Month><Day>13</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>7</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>10</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>7</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31323661</ArticleId><ArticleId IdType="doi">10.1093/ejcts/ezz139</ArticleId><ArticleId IdType="pii">5481174</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">31323631</PMID><DateRevised><Year>2019</Year><Month>07</Month><Day>19</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1933-0693</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2019</Year><Month>Jul</Month><Day>19</Day></PubDate></JournalIssue><Title>Journal of neurosurgery</Title><ISOAbbreviation>J Neurosurg</ISOAbbreviation></Journal>Letter to the Editor. Heterogeneous hypothalamic adhesion among third ventricle craniopharyngiomas. | Right ventricular pressure overload, which can result in restrictive right ventricular physiology, predicts slow recovery after biventricular repair of congenital heart defects. The goal of the study was to assess how extubation in the operating room influences the postoperative course in these patients.</AbstractText>Between January 2013 and June 2017, a total of 65 children [median age 0.96 (0.13-9.47) years; median weight 8 (3.05-25.8) kg] with right ventricular pressure overload underwent an intracardiac correction. The most common malformations were tetralogy of Fallot (n = 34) and double outlet right ventricle with pulmonary stenosis (n = 11). The patients were divided into 2 groups: the first (n = 36) comprised late extubated (LE) and the second (n = 29), early extubated (EE) children, immediately after chest closure in the operating room. Preoperative, perioperative and postoperative records were analysed retrospectively.</AbstractText>Children who had EE had a lower heart rate (EE 124.2 vs LE 133.6 bpm; P = 0.03), higher arterial blood pressure (systolic: EE 87.9 ± 9.35 vs LE 81.4 ± 12.0 mmHg; P = 0.029; diastolic: EE 51.1 ± 6.5 vs LE 45.9 ± 6.64 mmHg; P = 0.003), lower central venous pressure (EE 8.6 ± 1.89 mmHg vs LE 9.9 ± 2.42 mmHg; P = 0.03), fewer pleural effusions in the first 6 postoperative days (EE 1.38 ml/kg/day vs LE 5.98 ml/kg/day; P = 0.009), shorter time of dopamine support ≥3 μg/kg (EE 7.29 ± 12.26 h vs LE 34.78 ± 38.05 h, P < 0.001), shorter stays in the intensive care unit (EE 2.7 ± 2.67 vs LE 5.0 ± 4.77 days, P = 0.001) and hospital (EE 11.8 ± 4.79 vs LE 15.5 ± 7.8 days; P = 0.022).</AbstractText>Extubation in the operating room of children with right ventricular pressure overload undergoing biventricular correction is feasible and safe and has a beneficial effect on the postoperative course.</AbstractText>© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.</CopyrightInformation> |
2,328,807 | Cine MRI analysis by deep learning of optical flow: Adding the temporal dimension. | Accurate segmentation of the left ventricle (LV) from cine magnetic resonance imaging (MRI) is an important step in the reliable assessment of cardiac function in cardiovascular disease patients. Several deep learning convolutional neural network (CNN) models have achieved state-of-the-art performances for LV segmentation from cine MRI. However, most published deep learning methods use individual cine frames as input and process each frame separately. This approach entirely ignores an important visual clue-the dynamic cardiac motion along the temporal axis, which radiologists observe closely when viewing cine MRI. To imitate the approach of experts, we propose a novel U-net-based method (OF-net) that integrates temporal information from cine MRI into LV segmentation. Our proposed network adds the temporal dimension by incorporating an optical flow (OF) field to capture the cardiac motion. In addition, we introduce two additional modules, a LV localization module and an attention module, that provide improved LV detection and segmentation accuracy, respectively. We evaluated OF-net on the public Cardiac Atlas database with multicenter cine MRI data. The results showed that OF-net achieves an average perpendicular distance (APD) of 0.90±0.08 pixels and a Dice index of 0.95±0.03 for LV segmentation in the middle slices, outperforming the classical U-net model (APD 0.92±0.04 pixels, Dice 0.94±0.16, p < 0.05). Specifically, the proposed method enhances the temporal continuity of segmentation at the apical and basal slices, which are typically more difficult to segment than middle slices. Our work exemplifies the ability of CNN to "learn" from expert experience when applied to specific analysis tasks. |
2,328,808 | Sex-Based Mhrt Methylation Chromatinizes MeCP2 in the Heart.<Pagination><StartPage>288</StartPage><EndPage>301</EndPage><MedlinePgn>288-301</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.isci.2019.06.031</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S2589-0042(19)30214-7</ELocationID><Abstract><AbstractText>In the heart, primary microRNA-208b (pri-miR-208b) and Myheart (Mhrt) are long non-coding RNAs (lncRNAs) encoded by the cardiac myosin heavy chain genes. Although preclinical studies have shown that lncRNAs regulate gene expression and are protective for pathological hypertrophy, the mechanism underlying sex-based differences remains poorly understood. In this study, we examined DNA- and RNA-methylation-dependent regulation of pri-miR-208b and Mhrt. Expression of pri-miR-208b is elevated in the left ventricle of the female heart. Despite indistinguishable DNA methylation between sexes, the interaction of MeCP2 on chromatin is subject to RNase digestion, highlighting that affinity of the methyl-CG reader is broader than previously thought. A specialized procedure to isolate RNA from soluble cardiac chromatin emphasizes sex-based affinity of an MeCP2 co-repressor complex with Rest and Hdac2. Sex-specific Mhrt methylation chromatinizes MeCP2 at the pri-miR-208b promoter and extends the functional relevance of default transcriptional suppression in the heart.</AbstractText><CopyrightInformation>Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>K N</LastName><ForeName>Harikrishnan</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Epigenetics in Human Health and Disease, Central Clinical School, Faculty of Medicine, Monash University, Melbourne, VIC 3004, Australia; Baker Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia; Department of Clinical Pathology, The University of Melbourne, Parkville, VIC 3010, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Okabe</LastName><ForeName>Jun</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Epigenetics in Human Health and Disease, Central Clinical School, Faculty of Medicine, Monash University, Melbourne, VIC 3004, Australia; Baker Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mathiyalagan</LastName><ForeName>Prabhu</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Baker Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Khan</LastName><ForeName>Abdul Waheed</ForeName><Initials>AW</Initials><AffiliationInfo><Affiliation>Epigenetics in Human Health and Disease, Central Clinical School, Faculty of Medicine, Monash University, Melbourne, VIC 3004, Australia; Baker Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia; Department of Clinical Pathology, The University of Melbourne, Parkville, VIC 3010, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jadaan</LastName><ForeName>Sameer A</ForeName><Initials>SA</Initials><AffiliationInfo><Affiliation>Epigenetics in Human Health and Disease, Central Clinical School, Faculty of Medicine, Monash University, Melbourne, VIC 3004, Australia; Baker Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia; Department of Clinical Pathology, The University of Melbourne, Parkville, VIC 3010, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sarila</LastName><ForeName>Gulcan</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Epigenetics in Human Health and Disease, Central Clinical School, Faculty of Medicine, Monash University, Melbourne, VIC 3004, Australia; Baker Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ziemann</LastName><ForeName>Mark</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Epigenetics in Human Health and Disease, Central Clinical School, Faculty of Medicine, Monash University, Melbourne, VIC 3004, Australia; Baker Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Khurana</LastName><ForeName>Ishant</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Epigenetics in Human Health and Disease, Central Clinical School, Faculty of Medicine, Monash University, Melbourne, VIC 3004, Australia; Baker Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Maxwell</LastName><ForeName>Scott S</ForeName><Initials>SS</Initials><AffiliationInfo><Affiliation>Epigenetics in Human Health and Disease, Central Clinical School, Faculty of Medicine, Monash University, Melbourne, VIC 3004, Australia; Baker Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Du</LastName><ForeName>Xiao-Jun</ForeName><Initials>XJ</Initials><AffiliationInfo><Affiliation>Baker Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>El-Osta</LastName><ForeName>Assam</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Epigenetics in Human Health and Disease, Central Clinical School, Faculty of Medicine, Monash University, Melbourne, VIC 3004, Australia; Baker Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia; Department of Clinical Pathology, The University of Melbourne, Parkville, VIC 3010, Australia; Hong Kong Institute of Diabetes and Obesity, Prince of Wales Hospital, The Chinese University of Hong Kong, 3/F Lui Che Woo Clinical Sciences Building, 30-32 Ngan Shing Street, Sha Tin, Hong Kong SAR; University College Copenhagen, Faculty of Health, Department of Technology, Biomedical Laboratory Science, Copenhagen, Denmark. Electronic address: sam.el-osta@monash.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>06</Month><Day>27</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>iScience</MedlineTA><NlmUniqueID>101724038</NlmUniqueID><ISSNLinking>2589-0042</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Molecular Genetics</Keyword><Keyword MajorTopicYN="N">Molecular Mechanism of Gene Regulation</Keyword><Keyword MajorTopicYN="N">Molecular Physiology</Keyword></KeywordList><CoiStatement>The authors declare there is no competing interests.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>4</Month><Day>30</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2019</Year><Month>5</Month><Day>13</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>6</Month><Day>20</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>7</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>7</Month><Day>20</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>7</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31323475</ArticleId><ArticleId IdType="pmc">PMC6639684</ArticleId><ArticleId IdType="doi">10.1016/j.isci.2019.06.031</ArticleId><ArticleId IdType="pii">S2589-0042(19)30214-7</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Aguilo F., Li S., Balasubramaniyan N., Sancho A., Benko S., Zhang F., Vashisht A., Rengasamy M., Andino B., Chen C.H. 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Although preclinical studies have shown that lncRNAs regulate gene expression and are protective for pathological hypertrophy, the mechanism underlying sex-based differences remains poorly understood. In this study, we examined DNA- and RNA-methylation-dependent regulation of pri-miR-208b and Mhrt. Expression of pri-miR-208b is elevated in the left ventricle of the female heart. Despite indistinguishable DNA methylation between sexes, the interaction of MeCP2 on chromatin is subject to RNase digestion, highlighting that affinity of the methyl-CG reader is broader than previously thought. A specialized procedure to isolate RNA from soluble cardiac chromatin emphasizes sex-based affinity of an MeCP2 co-repressor complex with Rest and Hdac2. Sex-specific Mhrt methylation chromatinizes MeCP2 at the pri-miR-208b promoter and extends the functional relevance of default transcriptional suppression in the heart.<CopyrightInformation>Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>K N</LastName><ForeName>Harikrishnan</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Epigenetics in Human Health and Disease, Central Clinical School, Faculty of Medicine, Monash University, Melbourne, VIC 3004, Australia; Baker Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia; Department of Clinical Pathology, The University of Melbourne, Parkville, VIC 3010, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Okabe</LastName><ForeName>Jun</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Epigenetics in Human Health and Disease, Central Clinical School, Faculty of Medicine, Monash University, Melbourne, VIC 3004, Australia; Baker Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mathiyalagan</LastName><ForeName>Prabhu</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Baker Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Khan</LastName><ForeName>Abdul Waheed</ForeName><Initials>AW</Initials><AffiliationInfo><Affiliation>Epigenetics in Human Health and Disease, Central Clinical School, Faculty of Medicine, Monash University, Melbourne, VIC 3004, Australia; Baker Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia; Department of Clinical Pathology, The University of Melbourne, Parkville, VIC 3010, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jadaan</LastName><ForeName>Sameer A</ForeName><Initials>SA</Initials><AffiliationInfo><Affiliation>Epigenetics in Human Health and Disease, Central Clinical School, Faculty of Medicine, Monash University, Melbourne, VIC 3004, Australia; Baker Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia; Department of Clinical Pathology, The University of Melbourne, Parkville, VIC 3010, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sarila</LastName><ForeName>Gulcan</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Epigenetics in Human Health and Disease, Central Clinical School, Faculty of Medicine, Monash University, Melbourne, VIC 3004, Australia; Baker Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ziemann</LastName><ForeName>Mark</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Epigenetics in Human Health and Disease, Central Clinical School, Faculty of Medicine, Monash University, Melbourne, VIC 3004, Australia; Baker Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Khurana</LastName><ForeName>Ishant</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Epigenetics in Human Health and Disease, Central Clinical School, Faculty of Medicine, Monash University, Melbourne, VIC 3004, Australia; Baker Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Maxwell</LastName><ForeName>Scott S</ForeName><Initials>SS</Initials><AffiliationInfo><Affiliation>Epigenetics in Human Health and Disease, Central Clinical School, Faculty of Medicine, Monash University, Melbourne, VIC 3004, Australia; Baker Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Du</LastName><ForeName>Xiao-Jun</ForeName><Initials>XJ</Initials><AffiliationInfo><Affiliation>Baker Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>El-Osta</LastName><ForeName>Assam</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Epigenetics in Human Health and Disease, Central Clinical School, Faculty of Medicine, Monash University, Melbourne, VIC 3004, Australia; Baker Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC 3004, Australia; Department of Clinical Pathology, The University of Melbourne, Parkville, VIC 3010, Australia; Hong Kong Institute of Diabetes and Obesity, Prince of Wales Hospital, The Chinese University of Hong Kong, 3/F Lui Che Woo Clinical Sciences Building, 30-32 Ngan Shing Street, Sha Tin, Hong Kong SAR; University College Copenhagen, Faculty of Health, Department of Technology, Biomedical Laboratory Science, Copenhagen, Denmark. Electronic address: sam.el-osta@monash.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>06</Month><Day>27</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>iScience</MedlineTA><NlmUniqueID>101724038</NlmUniqueID><ISSNLinking>2589-0042</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Molecular Genetics</Keyword><Keyword MajorTopicYN="N">Molecular Mechanism of Gene Regulation</Keyword><Keyword MajorTopicYN="N">Molecular Physiology</Keyword></KeywordList><CoiStatement>The authors declare there is no competing interests.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>4</Month><Day>30</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2019</Year><Month>5</Month><Day>13</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>6</Month><Day>20</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>7</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>7</Month><Day>20</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>7</Month><Day>20</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">31323475</ArticleId><ArticleId IdType="pmc">PMC6639684</ArticleId><ArticleId IdType="doi">10.1016/j.isci.2019.06.031</ArticleId><ArticleId IdType="pii">S2589-0042(19)30214-7</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Aguilo F., Li S., Balasubramaniyan N., Sancho A., Benko S., Zhang F., Vashisht A., Rengasamy M., Andino B., Chen C.H. 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Physiol. 2003;285:H2688–H2693.</Citation><ArticleIdList><ArticleId IdType="pubmed">12933346</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Curated"><PMID Version="1">31322517</PMID><DateCompleted><Year>2019</Year><Month>10</Month><Day>29</Day></DateCompleted><DateRevised><Year>2019</Year><Month>10</Month><Day>29</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">1512-0112</ISSN><JournalIssue CitedMedium="Internet"><Issue>290</Issue><PubDate><Year>2019</Year><Month>May</Month></PubDate></JournalIssue><Title>Georgian medical news</Title><ISOAbbreviation>Georgian Med News</ISOAbbreviation></Journal><ArticleTitle>GENDER DIFFERENCES OF STRUCTURAL AND FUNCTIONAL CHANGES, AND LEFT VENTRICULAR MYOCARDIAL REMODELING IN PATIENTS WITH AORTIC VALVE CALCIFICATION.</ArticleTitle><Pagination><StartPage>63</StartPage><EndPage>68</EndPage><MedlinePgn>63-68</MedlinePgn></Pagination><Abstract>Little is known about the gender differences of left ventricular (LV) remodeling in patients with aortic valve calcification (AVC). The aim was to assess gender differences of structure functional changes and LV myocardial remodeling in patients with AVC depending on the type of valve lesion. 293 patients (131 men) with revealed AVC by transthoracic echocardioscopy without aortic stenosis and 76 patients (50 men) without AVC were examined. Men had normal geometry of LV more often than women (15.7% vs. 4.4 % in isolated AVC and 11.9% vs. 2.8 % in combined lesion of aortic valve (AV) and mitral valves ring (MVR), р<0.052), and eccentric hypertrophy was registered more often in man with combined AV and MVR lesion (38.1% vs. 15.5 % in women with combined AV and MVR lesion and vs. 20.2 % in men with isolated AVC, р<0.029). LV systolic function was worse in men with combined valves lesion (ejection fraction was 54.0 (48.0; 65.0) vs. 66.0 (60.0; 71.0) % in women with combined valves lesion and vs. 63.0 (55.0; 70.0) % in men with isolated AVC, р<0.022). Men with combined valves lesion also had a larger right ventricle (RV) size (RV index was 1.3 (1.2; 1.5) vs. 1.2 (1.1; 1.4) cm/m2 in women with combined valves lesion and vs. 1.2 (1.1; 1.4) cm/m2 in men with isolated AVC, р<0.036) and had tricuspid regurgitation more often (76.2% vs. 56.3 % in women with combined valves lesion and vs. 58.4 % in men with isolated AVC, р<0.029). Women had higher peak aortic jet velocity (1.5 (1.4; 1.7) vs. 1.4 (1.2; 1.6) m/s in man, р<0.0001). Dominating models of LV remodeling in women were concentric, mainly concentric hypertrophy (61.5% vs. 31.5 % in men in groups with isolated AVC and 64.8% vs. 31.0 % in combined valves lesion groups, р<0.001). Also women had a higher left auricle index than men (2.3 (2.0; 2.5) vs. 2.1 (1.9; 2.4) cm/m2, р<0.015). There were revealed differences in distribution of LV remodeling types depending on the gender and the type of valve lesion. |
2,328,809 | Human Cord Blood-Derived Unrestricted Somatic Stem Cell Infusion Improves Neurobehavioral Outcome in a Rabbit Model of Intraventricular Hemorrhage. | Intraventricular hemorrhage (IVH) is a severe complication of preterm birth, which leads to hydrocephalus, cerebral palsy, and mental retardation. There are no available therapies to cure IVH, and standard treatment is supportive care. Unrestricted somatic stem cells (USSCs) from human cord blood have reparative effects in animal models of brain and spinal cord injuries. USSCs were administered to premature rabbit pups with IVH and their effects on white matter integrity and neurobehavioral performance were evaluated. USSCs were injected either via intracerebroventricular (ICV) or via intravenous (IV) routes in 3 days premature (term 32d) rabbit pups, 24 hours after glycerol-induced IVH. The pups were sacrificed at postnatal days 3, 7, and 14 and effects were compared to glycerol-treated but unaffected or nontreated control. Using in vivo live bioluminescence imaging and immunohistochemical analysis, injected cells were found in the injured parenchyma on day 3 when using the IV route compared to ICV where cells were found adjacent to the ventricle wall forming aggregates; we did not observe any adverse events from either route of administration. The injected USSCs were functionally associated with attenuated microglial infiltration, less apoptotic cell death, fewer reactive astrocytes, and diminished levels of key inflammatory cytokines (TNFα and IL1β). In addition, we observed better preservation of myelin fibers, increased myelin gene expression, and altered reactive astrocyte distribution in treated animals, and this was associated with improved locomotor function. Overall, our findings support the possibility that USSCs exert anti-inflammatory effects in the injured brain mitigating many detrimental consequences associated with IVH. Stem Cells Translational Medicine 2019;8:1157-1169. |
2,328,810 | Neuroacanthocytosis: a case report of chorea-acanthocytosis. | Neuroacanthocytosis is a rare progressive neurodegenerative disease, including Chorea-acanthocytosis, McLeod syndrome, Huntington's disease-like 2, and pantothenate kinase-associated neurodegeneration, where Chorea-acanthocytosis occupies the main entity of this disease group. Here, a classic case of Chorea-acanthocytosis is reported that exhibited gradually deteriorating abnormal movements of limbs and face, swallowing difficulty, and lip and cheek biting for the past two years. Peripheral blood smears revealed that 35% of the red blood cells were acanthocytes and electron microcopy scans clearly showed the morphology of acanthocytes. VPS13A gene sequencing found a heterozygous novel VPS13A gene mutation (c.80dupT). Brain magnetic resonance imaging scans showed moderate anterior horn dilation of lateral ventricles and bilateral atrophy of the head of caudate nucleus. Several suggestive features are summarized to provide diagnostic clues for Chorea-acanthocytosis and facilitate future diagnosis and treatment. |
2,328,811 | Does gender influence cardiovascular remodeling in C57BL/6J mice fed a high-fat, high-sucrose and high-salt diet? | Animal models are widely used to study the physiopathology of human diseases. However, the influence of gender on modern society diet style-induced cardiovascular disease has not thus far been explored in these models. Thus, this study investigated cardiovascular remodelling in C57BL/6J mice fed a diet rich in saturated fat, sucrose and salt, evaluating gender effect on this process. Male and female C57BL/6J mice were fed AIN93M diet or a modified AIN93M rich in fat, sucrose and salt (HFSS) for 12 weeks. Body mass, water and food intake and cardiovascular remodelling were assessed. The HFSS diet did not lead to body mass gain or glucose metabolism disturbance as assessed by serum glucose, insulin and oral glucose tolerance test. However, female mice on a HFSS diet had increased visceral and subcutaneous adiposity. Only male mice displayed heart hypertrophy. The left ventricle was not hypertrophied in either male or female mice, but its lumen was dilated. Intramyocardial arteries and the thoracic aorta showed media thickening in male mice, but in the female it was only observed in the thoracic aorta. Finally, intramyocardial artery dilation was present in both genders, but not in the aorta. Therefore changes in LV dimensions and arterial remodelling were influenced by both gender and the HFSS diet. In conclusion, male and female C57BL/6J mice suffered cardiovascular remodelling after 12 weeks of HFSS feeding, although they did not develop obesity or diabetes. Sexual dimorphism occurred in response to diet for body adiposity, heart hypertrophy and intramyocardial artery remodelling. |
2,328,812 | HACE1 deficiency leads to structural and functional neurodevelopmental defects. | We aim to characterize the causality and molecular and functional underpinnings of HACE1</i> deficiency in a mouse model of a recessive neurodevelopmental syndrome called spastic paraplegia and psychomotor retardation with or without seizures (SPPRS).</AbstractText>By exome sequencing, we identified 2 novel homozygous truncating mutations in HACE1</i> in 3 patients from 2 families, p.Q209* and p.R332*. Furthermore, we performed detailed molecular and phenotypic analyses of Hace1</i> knock-out (KO) mice and SPPRS patient fibroblasts.</AbstractText>We show that Hace1</i> KO mice display many clinical features of SPPRS including enlarged ventricles, hypoplastic corpus callosum, as well as locomotion and learning deficiencies. Mechanistically, loss of HACE1 results in altered levels and activity of the small guanosine triphosphate (GTP)ase, RAC1. In addition, HACE1 deficiency results in reduction in synaptic puncta number and long-term potentiation in the hippocampus. Similarly, in SPPRS patient-derived fibroblasts, carrying a disruptive HACE1</i> mutation resembling loss of HACE1 in KO mice, we observed marked upregulation of the total and active, GTP-bound, form of RAC1, along with an induction of RAC1-regulated downstream pathways.</AbstractText>Our results provide a first animal model to dissect this complex human disease syndrome, establishing the first causal proof that a HACE1 deficiency results in decreased synapse number and structural and behavioral neuropathologic features that resemble SPPRS patients.</AbstractText> |
2,328,813 | Use of idarucizumab for dabigatran reversal in cardiac tamponade during atrial fibrillation ablation: A case report. | It is known that the efficacy of catheter ablation for atrial fibrillation (AF) is high, but cardiac tamponade may occur in 1-2% cases. Even in such cases, fatal condition can be avoided by appropriate drainage, but reversal of anticoagulation therapy might also be necessary. Here, we report a case of use of idarucizumab for cardiac tamponade during AF ablation. Although the drainage with pericardial centesis should be selected, we could not perform because echo free space was too thin at least at the precordial or apical side of the ventricle. Fortunately, dabigatran reversal by idarucizumab suppressed cardiac tamponade progress and the patient recovered without undergoing any invasive procedures. The pericardial drainage must be the principal therapy for cardiac tamponade, but reversal of anticoagulant might be helpful for patients' recovery. It might be thought that dabigatran, the only direct oral anticoagulant with a specific reversal agent, should be the safest choice in case of risk for bleeding complications such as AF ablation. <<b>Learning objective:</b> Cardiac tamponade is one of the complications of catheter ablation for atrial fibrillation (AF). In such cases, fatal condition can be avoided by appropriate drainage, but reversal of anticoagulation therapy might be necessary. Drainage with pericardial centesis was not selected because echo free space was too thin. Dabigatran reversal by idarucizumab suppressed cardiac tamponade progress. It was thought that dabigatran would be the safest choice in case of bleeding complications during AF ablation.>. |
2,328,814 | Development and evaluation of a craniocerebral model with tactile-realistic feature and intracranial pressure for neurosurgical training. | In this article, a craniocerebral model is introduced for neurosurgical training, which is patient-specific, tactile-realistic, and with adjustable intracranial pressure.</AbstractText>The patient-specific feature is achieved by modeling from CT scans and magnetic resonance images (MRI). The brain tissue model is built by the hydrogel casting technique, while scalp, skull, vasculature, and lateral ventricles are all-in-one fabricated by three-dimensional (3D) printing. A closed-loop system is integrated to monitor and control the intracranial pressure. 3D measurements, mechanical tests, and simulated external ventricular drain (EVD) placement procedures are conducted on the model.</AbstractText>A neurosurgical training model is completed with high accuracy (mean deviation 0.36 mm). The hydrogel brain tissue has a stiffness more similar to that of a real brain than the common 3D printed materials. The elasticity modulus of hydrogel brain tissue model is E=25.71 kPa, compared with our softest 3D printed material with E=1.14×103</sup> kPa. Ten experienced surgeons rate the tactile realness of the neurosurgical training model at an average point of 4.25 on a scale from 1 (strongly negative) to 5 (strongly positive). The neurosurgical training model is also rated to be realistic in size (4.82), anatomy (4.70), and effective as an aid to improve blind EVD placement skills (4.65).</AbstractText>The neurosurgical training model can provide trainee surgeons with realistic experience in both tactile feedbacks and craniocerebral anatomy, improving their surgical skills.</AbstractText>© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.</CopyrightInformation> |
2,328,815 | Upfront chemotherapy followed by response adaptive radiotherapy for intracranial germinoma: Prospective multicenter cohort study. | To assess the efficacy of upfront chemotherapy followed by response-adapted reduced-dose/reduced-volume radiotherapy (RT) for intracranial germinoma.</AbstractText>Ninety-one patients from five institutions were registered in the KSPNO G051/G081 Protocol. Germinomas were classified as solitary or multiple/disseminated diseases, and upfront chemotherapy was administered. For all patients with multiple or disseminated disease, and patients with partial response after chemotherapy, 19.5-24 Gy of craniospinal irradiation plus 10.8-19.8 Gy of tumor bed boost were planned. For patients with complete response (CR), reduced-dose RT (30.6 Gy) was planned, along with a reduced field for solitary lesions.</AbstractText>The median patient age was 14 (range, 3-30) years. Sixty-five patients (71.4%) had a solitary lesion. The median follow-up duration was 67.9 (range, 6.6-119.3) months. Recurrence was not observed in 32 patients in the protocol compliant group. Four patients (4.4%) in the protocol non-compliant group experienced relapse after CR and one patient died of the disease. The 5-year and 7-year overall survival rates were 98.8% and 98.8%, while the corresponding event-free survival rates were 96.6% and 93.8%, respectively. All three patients with basal ganglia germinomas who were treated with local RT experienced recurrence outside the RT field. Among the 23 patients with pineal or suprasellar lesions who received whole-ventricle RT, there was no recurrence.</AbstractText>Currently used upfront chemotherapy followed by reduced-dose, reduced-volume RT appears acceptable, when whole-ventricle RT for pineal or suprasellar tumors and, at minimum, whole-brain RT for basal ganglia/thalamus lesions are applied.</AbstractText>Copyright © 2019 Elsevier B.V. All rights reserved.</CopyrightInformation> |
2,328,816 | Pineal region tumors: Long-term results of endoscopic third ventriculostomy and concurrent tumor biopsy with a single entry approach in a series of 64 cases. | Endoscopic third ventriculostomy and concurrent biopsy is increasingly used in management of the pineal region tumors. Our objective was to assess the results of single entry approach to surgically manage the tumors of the pineal region.</AbstractText>A retrospective study was designed, and a series of 64 consecutive patients (31 male, 33 female) with pineal region tumor undergoing endoscopic third ventriculostomy and concurrent biopsy of the tumor was undertaken.</AbstractText>A total of 64 patients underwent simultaneous endoscopic third ventriculostomy and biopsy of the pineal tumors with a single entry approach. A positive initial diagnosis was established in 97% of patients. 5 patients (7%) required the insertion of an external ventricular drain which was removed in all patients after 72 h but in one case (1%) undergoing permanent VP shunt insertion. The postoperative complications were divided into two transient and permanent complications. The transient complications included intraventricular hemorrhage (18%), seizure (1 to two episodes of seizure) (5%), diabetes insipidus (3%) and meningitis (3%) all were successfully managed. The only permanent complication was memory deficits occurred in one patient (1%). There was no mortality rate in current study.</AbstractText>The results of this study support the safety and efficacy of endoscopic third ventriculostomy and concurrent biopsy of the pineal region tumors as a less invasive surgical method associated with low morbidity and mortality rate. Our data demonstrated how simultaneous endoscopic third ventriculostomy and biopsy of the pineal region tumors with a single entry approach can produce favorable results.</AbstractText>Copyright © 2019 Elsevier B.V. All rights reserved.</CopyrightInformation> |
2,328,817 | Roles of neuroimage in toxic encephalopathy induced by 1, 2-Dichloroethane. | Toxic encephalopathy induced by exposure to 1,2-dichloroethane(1,2-DCE) may result in central nervous system (CNS) abnormalities. The study was to describe the clinical and neuroimaging features in toxic encephalopathy induced by 1, 2-DCE.</AbstractText>The study evaluates six patients with clinical symptoms and neuroimaging who are exposed to 1, 2-DCE, including medical and neurologic examination, CT imaging, proton MR spectroscopy (MRS), Diffusion weighted MR (DW MR) and T1-and T2-weighted MR imaging.</AbstractText>All patients who had been exposed to DCE subsequently had seizures or symptoms of intracranial hypertension,including headache, nausea, and vomiting. CT findings: All lesions appeared as low density and bilateral symmetry. The lesions appeared in white matter of cerebral hemisphere diffusely, bilateral cerebellar dentate nuclei, thalamus and globus pallidus. MRI features: All lesions showed high signal intensity on T2WI. Cerebral sulci swelling and compressed or occluded ventricles were seen on CT and MRI. DW MR images obtained at b = 1000s/mm2 revealed symmetrical high signal intensity changes. The apparent diffusion coefficient (ADC) values of lesions were decreased. MR spectroscopic findings established the spectral patterns: increased choline-containing compounds and decreased N-acetylaspartate.</AbstractText>The clinical symptoms of intracranial hypertension and the features of CT and MR imagings are useful for early diagnosis and prompt treatment in toxic encephalopathy.</AbstractText>Copyright © 2019 Elsevier B.V. All rights reserved.</CopyrightInformation> |
2,328,818 | Automatic display of fetal brain planes and automatic measurements of fetal brain parameters by transabdominal three-dimensional ultrasound. | The primary purpose of this study was to evaluate the effectiveness of a three-dimensional (3D) software tool (smart planes) for displaying fetal brain planes, and the secondary purpose was to evaluate its accuracy in performing automatic measurements.</AbstractText>This prospective study included singleton fetuses with a gestational age (GA) greater than 18 weeks. Transabdominal two-dimensional ultrasound (2DUS) and 3D smart planes images were respectively used to obtain the basic planes of the fetal brain, with five parameters measured. The images, by either two-dimensional (2D) manual or 3D automatic operation, were reviewed by two experienced sonographers. The agreements between two measurements were analyzed.</AbstractText>A total of 226 cases were included. The rates of successful detection by automatic display were as high as 80%. There was substantial agreement between the measurements of the biparietal diameter, head circumference and transcerebellar diameter, but poor agreement between the measurements of cisterna magna and lateral ventricle width.</AbstractText>Smart Planes might be valuable for the rapid evaluation of fetal brain, because it simplifies the evaluation process. However, the technology requires improvement. In addition, this technology cannot replace the conventional manual US scans; it can only be used as an additional approach.</AbstractText>© 2019 Wiley Periodicals, Inc.</CopyrightInformation> |
2,328,819 | Spinal paraganglioma presenting as normal pressure hydrocephalus: a rare occurrence. | <b>Objective:</b> We report a 63 years old female who presented with confusion, urinary retention and gait disturbances.<b>Method:</b> CT head shows communicating hydrocephalus. Spinal MRI demonstrated an L5- S1 intradural lesion.<b>Result:</b> Histopathology proved it to be paraganglioma. Postoperative CT head showed reduction in size of ventricles. Association between spinal tumors and hydrocephalus is known but occurs infrequently.<b>Conclusion:</b> The presence of an intraspinal tumor must be kept in mind as a possible cause of the hydrocephalus. |
2,328,820 | Intra-aortic Balloon Pump for Cesarean Hysterectomy and Massive Hemorrhage in a Parturient with Placenta Accreta and Pulmonary Embolus. | During cesarean hysterectomy for a placenta accreta, a 36-year-old parturient underwent a massive resuscitation for profound bleeding and also suffered a pulmonary embolus leading to cardiac arrest. Chest compressions and epinephrine were required for resucitation. When surgery was complete, she was taken to the intensive care unit on an epinephrine infusion and inhaled nitric oxide but was brought back to the operating room after 3 h for surgical exploration. Echocardiography revealed a poorly contracting left ventricle, and an intra-aortic balloon pump was inserted. She gradually recovered full function and was discharged home after 35 days. |
2,328,821 | Cardiac Glucose and Fatty Acid Transport After Experimental Mono- and Polytrauma. | The aim of this study was to define the influence of trauma on cardiac glucose and fatty acid transport. The effects were investigated in vivo in a porcine mono- and polytrauma model and in vitro in human cardiomyocytes, which were treated simultaneously with different inflammatory substances, mimicking posttraumatic inflammatory conditions.</AbstractText>In the porcine fracture- and polytrauma model, blood glucose concentrations were measured by blood gas analysis during an observation period of 72 h. The expression of cardiac glucose and fatty acid transporters in the left ventricle was determined by RT-qPCR and immunofluorescence. Cardiac and hepatic glycogen storage was examined. Furthermore, human cardiomyocytes were exposed to a defined trauma-cocktail and the expression levels of glucose- and fatty acid transporters were determined. Early after polytrauma, hyperglycemia was observed. After 48 and 72 h, pigs with fracture- and polytrauma developed hypoglycemia. The propofol demand significantly increased posttrauma. The hepatic glycogen concentration was reduced 72 h after trauma. Cardiac glucose and fatty acid transporters changed in both trauma models in vivo as well as in vitro in human cardiomyocytes in presence of proinflammatory mediators.</AbstractText>Monotrauma as well as polytrauma changed the cardiac energy transport by altering the expression of glucose and fatty acid transporters. In vitro data suggest that human cardiomyocytes shift to a state alike myocardial hibernation preferring glucose as primary energy source to maintain cardiac function.</AbstractText> |
2,328,822 | Rosette-forming glioneuronal tumor: an update. | Rosette-forming glioneuronal tumor (RGNT) is a rare and distinct primary nervous system tumor. The literature on this novel neoplasm is sparse and limited to mostly case reports. Reviews on the characteristics of this tumor are fewer and far between with the latest up to a decade old. We thus provide a comprehensive review of recent literature to characterize presenting symptoms, radiological evidence, treatment options, and prognosis of this novel neoplasm. A Medline search for case reports detailing primary rosette-forming glioneuronal tumors was performed. RGNTs are a benign tumor of indolent course with mixed glial and neurocytic components. There is a slight female predominance with mean age of presentation at 23.57 years. Headaches, visual disturbances, and nausea and vomiting are the most common symptoms. Most RGNTs have solid and cystic components, arising most frequently in the fourth ventricle or cerebellum. Management is usually through surgery with gross total resection (GTR) providing better prognosis. |
2,328,823 | Navigated neuroendoscopy combined with intraoperative magnetic resonance cysternography for treatment of arachnoid cysts. | Endoscopic cystocysternostomy or cystoventriculostomy is the treatment of choice in patients with symptomatic intracranial arachnoid cysts. There are no objective diagnostic tests for reliable intraoperative evaluation of the effectiveness of performed stomies. The aim of this prospective open-label study is to demonstrate for the first time the usefulness of intraoperative cysternography performed with the low-field 0.15-T magnetic resonance imager Polestar N20 during endoscopic cysternostomies. The study was performed in patients operated for middle fossa arachnoid cysts (n = 10), suprasellar cysts (n = 4), paraventricular or intraventricular cysts (n = 6), and a pineal cyst (n = 1). The operations were performed with use of a navigated neuroendoscope. Intraoperative magnetic resonance (iMR) cysternography was performed before and after the cystostomy. In each case, iMR cysternography was safe and could show clearly the cyst morphology and the effectiveness of performed endoscopic cystostomies. In six cases, iMR cysternography had a significant influence of the surgical decision (p = 0.027). The rate of inconsistency between the intraoperative observations and iMR imaging-based findings was 29%. A good contrast flow through the fenestrated cyst walls correlated with a good long-term clinical outcome (ρ = 0.54, p < 0.05) and good long-term radiological outcome (ρ = 0.72, p < 0.05). Intraoperative low-field MR cysternography is a safe and reliable method for assessment of the efficacy of performed endoscopic cystostomies and has significant influence on the surgical decision. It may be reliably used for prediction of the long-term clinical and radiological outcome. |
2,328,824 | Tension Pneumocephalus: A Rare Complication of Transsphenoidal Resection of a Pituitary Macroadenoma. | Tension pneumocephalus (TP) is described as the presence of a large amount of air in the cranial cavity, compressing the parenchyma and ventricles. It is a rare neurosurgical emergency and has been reported in only a handful of cases as a complication of transsphenoidal resection of a pituitary adenoma. Our reported case is an addition to the series of those cases. A 60-year-old male patient underwent transsphenoidal resection of a pituitary macroadenoma. Computed tomography (CT) of the head performed post-procedure showed post-surgical changes with no identification of any acute intracerebral processes. On postoperative Day 2, the patient had a bout of sneezing and since that time, he was noted to be more altered in terms of his mentation and lethargic with no focal neurological deficits. A repeat CT of the head showed a large amount of air in the intracranial cavity compressing the brain parenchyma with slit-like appearances of the cerebral ventricles. The patient underwent emergent bifrontal air evacuation through burr holes. A cerebrospinal fluid leak was also noted while reconstructing the skull base. A postoperative CT scan showed marked resolution of TP. The patient improved clinically, was discharged home five days later, and was monitored closely by the surgical team on an outpatient basis. |
2,328,825 | Frontal Occipital and Frontal Temporal Horn Ratios: Comparison and Validation of Head Ultrasound-Derived Indexes With MRI and Ventricular Volumes in Infantile Ventriculomegaly. | <b>OBJECTIVE.</b> The purpose of our study was to assess whether linear ventricular dimensions-specifically, the frontal occipital horn ratio (FOHR) and frontal temporal horn ratio (FTHR) obtained from ultrasound (US)-are reliable measures of ventriculomegaly in infants. Our hypothesis was that these US measures would show good correlation with linear ventricular indexes and ventricular volumes obtained from MRI. <b>MATERIALS AND METHODS.</b> We retrospectively identified 90 infants (age ≤ 6 months corrected gestational age) with ventriculomegaly from 2014 to 2017 who had a total of 100 sets of US and MRI studies performed in a 3-day period. FOHR and FTHR were independently measured on US and MRI by two pediatric radiologists and two pediatric neuroradiologists, respectively. Ventricular and brain volumes were segmented from the MR images, and the ventricle-to-intracranial volume ratio was calculated. MRI served as the reference standard. Intraclass correlation coefficients and Bland-Altman analyses were generated to evaluate interobserver and US-MRI concordance. We assessed correlation of the FOHR and FTHR with the ventricle-to-intracranial volume ratio. <b>RESULTS.</b> Bland-Altman plots of the FOHR and FTHR between US and MRI showed excellent concordance with a bias of 0.05 (95% CI, -0.04 to 0.14) and 0.03 (95% CI, -0.06 to 0.13), respectively. There was good-to-excellent interobserver concordance for FOHR and FTHR on head US or MRI (<i>r</i> = 0.86-0.96). There was good correlation between ventricle-to-intracranial volume ratios and US- and MRI-derived FOHRs and FTHRs (<i>r</i> = 0.79-0.87). <b>CONCLUSION.</b> FOHR and FTHR obtained from US in infants with ventriculomegaly have excellent interobserver concordance, are concordant with MRI-derived linear ratios, and correlate with MRI-derived ventricular volumes. Therefore, US-derived FOHR and FTHR are reliable indexes for clinical follow-up of infantile ventriculomegaly. |
2,328,826 | Left ventricular adaptation following orthotopic heart transplantation in children: A speckle tracking echocardiographic imaging study. | Evolution of left ventricle (LV) function in the pediatric OHT population has not been well described. Our hypothesis was that, in children following OHT without any rejection, there would be progressive normalization of LV size and function over 2 years.</AbstractText>LV function was evaluated using STE and conventional echo parameters at five time points in pediatric OHT patients without any rejection in the first 2 years following OHT and normal controls. LV global peak systolic longitudinal strain (LVPLS) and strain rate, LV peak systolic radial and circumferential strain (LVRS and LVCS), and strain rate were analyzed.</AbstractText>We had twenty two patients with median age at OHT of 1.27 years ( IQR 0.19, 5.6 years). The LVPLS (mean ± SD) was abnormal in the post-OHT echocardiograms at 1 week (-12.4 ± 3.7) and 1 month (-13.9 ± 3.7) and significantly improved at 6 months (-15.8 ± 3.2), 1 year (-15.7 ± 3.1), and 2 years (-17.8 ± 2.8). However, LVPLS remained below the normal group even at 2 years following OHT (-21.3 ± 1.76).</AbstractText>In children following OHT, despite the absence of rejection, strain values are significantly impaired in the initial months, improve progressively over the first 2 years but remain abnormal compared with healthy controls.</AbstractText>© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</CopyrightInformation> |
2,328,827 | Adult Neurogenesis in the Subventricular Zone and Its Regulation After Ischemic Stroke: Implications for Therapeutic Approaches. | Adult neurogenesis in the subventricular zone is a topic of intense research, since it has vast implications for the fundamental understanding of the neurobiology of the brain and its potential to being harnessed for therapy in various neurological disorders. Investigation of adult neurogenesis has been complicated by the difficulties with characterization of neural stem cells in vivo. However, recent single-cell transcriptomic studies provide more detailed information on marker expression in neural stem cells and their neuronal lineage, which hopefully will result in a more unified discussion. Regulation of the multiple biological steps in adult neurogenesis comprises intrinsic mechanisms as well as extrinsic factors which together orchestrate the process. In this review, we describe the regulating factors and their cellular sources in the physiological condition and provide an overview of the regulating factors mediating stroke-induced stimulation of neurogenesis in the subventricular zone. While there is ongoing debate about the longevity of active post-natal neurogenesis in humans, the subventricular zone has the capacity to upregulate neurogenesis in response to ischemic stroke. Though, the stroke-induced neurogenesis in humans does not seem to translate into adequate functional recovery, which opens discussion about potential treatment strategies to harness this neuroregenerative response. Various therapeutic approaches are explored in preclinical and clinical studies to target endogenous neurogenesis of which some are discussed in this review. |
2,328,828 | Cost-Effectiveness of Percutaneous Lymphatic Embolization for Management of Plastic Bronchitis. | Plastic bronchitis is a dreaded complication of single ventricle physiology occurring following palliation via Fontan procedure. Medical management of plastic bronchitis often fails, requiring heart transplantation. Percutaneous lymphatic embolization is an emerging treatment for plastic bronchitis.</AbstractText>To determine the cost-effectiveness of competing management strategies, a modified Markov model was constructed with patients transiting through treatments-medical management, lymphatic embolization, or heart transplantation from a hospital system perspective. Health state transitions were modeled using an institutional review board-approved retrospective review of the Children's Hospital of Pennsylvania's plastic bronchitis cohort. Medication pricing data were obtained from the National Inpatient Sample. Differences in costs and quality-adjusted life years (QALYs) over a five-year horizon for each group were determined. The incremental cost-effectiveness ratio was then calculated.</AbstractText>The mean cost of lymphatic embolization from procedure performance was US$340,941, US$385,841 for heart transplantation, and US$594,520 for medical management. The mean quality-adjusted survival of lymphatic embolization yielded an additional 0.66 QALYs (P</i> < .03) relative to heart transplantation and 1.3 (P</i> < .0001) relative to medical management. Orthotopic heart transplantation yielded an additional 0.66 QALYs (P</i> = .06) when comparing heart transplantation to medical management. Compared to medical management, lymphatic embolization generated an incremental cost-effectiveness ratio of US$192,105. Similarly, compared to heart transplantation, lymphatic embolization yielded an incremental cost-effectiveness ratio of US$68,030.</AbstractText>Of the available plastic bronchitis treatments, with a willingness to pay of US$150,000, lymphatic embolization produces an incremental cost-effectiveness ratio within the bounds considered to be cost-effective, potentially causing financial benefits to the health system.</AbstractText> |
2,328,829 | Partial Reconstitution of the Hypothalamo-Pituitary Axes After Pituitary Stalk Sectioning and Specific Magnetic Resonance Imaging Findings. | Pituitary stalk sectioning is only essential in cases of craniopharyngioma originating from the stalk or metastatic tumor to the stalk. Some patients can discontinue postoperative antidiuretic hormone (ADH) supplementation with special conditions.</AbstractText>Sixty-three patients with craniopharyngiomas who were treated by surgery with pituitary stalk sectioning were included in this study. Great care was taken to preserve the fine arteries running along the lateral walls of the third ventricle. Removal rates, change of endocrinologic status, and magnetic resonance imaging (MRI) findings were investigated.</AbstractText>Total removal was achieved in 52 of 54 patients in initial surgery (96.3%), and in 5 of 9 patients in retreatment (55.6%). ADH supplementation was required in all patients from the day of surgery, but was discontinued in 29 of 54 patients among the initial surgery group (53.7%) and in 2 of 9 patients among the retreatment group (22.2%). Preservation of thyroid hormone secretion was observed in 24 of 31 patients who could discontinue ADH (77.4%), but only in 12 of 32 patients who could not discontinue ADH (37.5%). Recovery from diabetes insipidus (DI) was significantly associated with preservation of thyroid function (P < 0.01). Postoperative MRI showed that part of the hypothalamus was enhanced in patients with recovery from DI.</AbstractText>Total removal was achieved in 91% of all cases. Half of the patients could discontinue ADH supplementation, which was associated with preservation of thyroid function. The findings of hypothalamic enhancement on postoperative MRI may be associated with recovery from DI.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,830 | Choroid plexus-derived miR-204 regulates the number of quiescent neural stem cells in the adult brain. | Regulation of adult neural stem cell (NSC) number is critical for lifelong neurogenesis. Here, we identified a post-transcriptional control mechanism, centered around the microRNA 204 (miR-204), to control the maintenance of quiescent (q)NSCs. miR-204 regulates a spectrum of transcripts involved in cell cycle regulation, neuronal migration, and differentiation in qNSCs. Importantly, inhibition of miR-204 function reduced the number of qNSCs in the subependymal zone (SEZ) by inducing pre-mature activation and differentiation of NSCs without changing their neurogenic potential. Strikingly, we identified the choroid plexus of the mouse lateral ventricle as the major source of miR-204 that is released into the cerebrospinal fluid to control number of NSCs within the SEZ. Taken together, our results describe a novel mechanism to maintain adult somatic stem cells by a niche-specific miRNA repressing activation and differentiation of stem cells. |
2,328,831 | Effect and Complications of Everolimus Use for Giant Cardiac Rhabdomyomas with Neonatal Tuberous Sclerosis. | Most cardiac rhabdomyomas with tuberous sclerosis (TS) are asymptomatic and spontaneously regress. However, some cases require surgical intervention due to arrhythmia and severe obstruction of cardiac inflow or outflow. We report herein a neonatal case of giant cardiac rhabdomyomas with TS and insufficient pulmonary blood flow from the right ventricle. Lipoprostaglandin E1 was necessary to maintain patency of the ductus arteriosus. We used everolimus, a mammalian target of rapamycin inhibitor, to diminish the cardiac rhabdomyomas. After treatment, the rhabdomyomas shrank rapidly, but the serum concentration of everolimus increased sharply (maximum serum trough level: 76.1 ng/mL) and induced complications including pulmonary hemorrhage, liver dysfunction, and acne. After the everolimus level decreased, the complications resolved. Everolimus may be a viable treatment option for rhabdomyomas, but its concentration requires close monitoring to circumvent complications associated with its use. |
2,328,832 | Leishmania hide-and-seek: Parasite amastigotes in the choroid plexus of a dog with neurological signs in an endemic municipality in Brazil. | A female adult mixed-breed stray dog presented with hind limb paraparesis and clinical signs of visceral leishmaniasis. The cerebrospinal fluid presented signs of blood-brain barrier disruption. Both spleen and brain were positive for Leishmania spp. DNA. Besides inflammation, in situ hybridization and immunohistochemistry (IHC) revealed the presence of intracellular amastigotes in the choroid plexus (CP). Despite other studies that revealed parasite DNA, the current study describes the presence of Leishmania within the brain of a naturally infected dog, specifically in CP, with no previous reports in the Americas, and suggests the CP as a possible pathway to parasite entry into the brain. |
2,328,833 | Epidemiology of Dandy-Walker Malformation in Europe: A EUROCAT Population-Based Registry Study. | Dandy-Walker (DW) malformation is a rare and severe congenital anomaly of the posterior fossa affecting the development of the cerebellum and the fourth ventricle.</AbstractText>The aim of this study was to investigate the epidemiology of DW malformation, using data from the European population-based registries of congenital anomalies in the European Surveillance of Congenital Anomalies network.</AbstractText>Anonymous individual data on cases of DW malformation diagnosed in 2002-2015 from 28 registries in 17 countries were included. Prevalence, prenatal detection rate, proportions and types of associated anomalies were estimated. Cases of DW variant were considered and analysed separately.</AbstractText>Out of 8,028,454 surveyed births we identified a total of 734 cases, including 562 DW malformation cases and 172 DW variant cases. The overall prevalence of DW malformation was 6.79 per 100,000 births (95% CI 5.79-7.96) with 39.2% livebirths, 4.3% foetal deaths from 20 weeks gestational age, and 56.5% terminations of pregnancy after prenatal diagnosis of foetal anomaly at any gestation (TOPFA). The livebirth prevalence was 2.74 per 100,000 births (95% CI 2.08-3.61). The prenatal detection rate was 87.6%. Two-hundred and seventy-three cases (48.6%) had an isolated cerebral anomaly and 24.2, 19.2 and 5.5% cases were associated with other structural non-cerebral anomalies, chromosomal anomalies and genetic syndromes respectively. The prevalence of DW variant was 2.08 per 100,000 (95% CI 1.39-3.13).</AbstractText>This European population-based study provides the epidemiological profile of DW malformation. All birth outcomes were analysed and TOPFA represented more than half of the cases. About 50% of the cases of DW malformation were associated with other non-cerebral anomalies. Large populations and all birth outcomes are essential in epidemiological studies of rare and severe congenital anomalies.</AbstractText>© 2019 S. Karger AG, Basel.</CopyrightInformation> |
2,328,834 | Are Hygromas and Hydrocephalus After Decompressive Craniectomy Caused by Impaired Brain Pulsatility, Cerebrospinal Fluid Hydrodynamics, and Glymphatic Drainage? Literature Overview and Illustrative Cases. | Poorly understood cranial fluid accumulations are frequently observed after decompressive craniectomy and often termed "external hydrocephalus." These findings are difficult to explain using traditional models of hydrocephalus.</AbstractText>Representative cases, clinical management, and literature overview are presented.</AbstractText>We present a hypothesis that abnormal cranial fluid accumulations develop after decompressive craniectomy in a vulnerable subset of patients as a result of 1) the large compliant cranial defect with durotomy causing reduced internal brain expansion, ventricular squeezing, and pulsatile cerebrospinal fluid (CSF) circulation; 2) impaired pulsatile CSF flow along major cerebral arteries and the adjoining perivascular spaces (Virchow-Robin spaces); 3) reduced clearance of interstitial fluid by the glymphatic system; and 4) redistribution of CSF from the subarachnoid space into the subdural and subgaleal compartments and the ventricles.</AbstractText>Closure of the cranial defect with cranioplasty improves cerebral blood flow and CSF pulsatile circulation and is frequently sufficient to resolve the external hydrocephalus.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,835 | 3-Dimensional Simulation Videography for Instructional Placement of Bedside External Ventricular Drains. | We present a narrated video simulation (Video 1) using 3-dimensional anatomic software demonstrating the proper landmarks and relevant neuroanatomy for successful bedside external ventricular drain placement. External ventricular drains are commonly inserted at the bedside for emergent intracranial pressure monitoring and/or treatment of elevated intracranial pressure by cerebrospinal fluid drainage.<sup>1</sup> Often, neurosurgical trainees perform this procedure early in their residency years.<sup>2,3</sup> The relationship of the ventricle to the external skull landmarks may be a difficult concept to grasp for junior trainees who have had limited procedural experience. Multiple catheter passes in attempt to cannulate the ventricle are associated with increased procedural risk to the patient.<sup>2,4</sup> Two common catheter misplacement locations leading to multiple catheter passes are lateral to the ventricle and anterior to the ventricle. In this video we highlight the relationship of the borders of the lateral ventricle to the insertion point at the skull during catheter placement. By using this resource for resident education, patient safety factors and resident procedural competence may be enhanced. |
2,328,836 | A Precursor to Multiloculated Hydrocephalus: Case Report and Review of Literature. | Multiloculated hydrocephalus (MH) is a challenging pathology for pediatric neurosurgeons, arising from various etiologies including intraventricular hemorrhage, infection, and overshunting. Although previous publications have discussed the potential etiology of this pathological process, including fibroglial webbing, no clear precursor has been proven. We present a case of MH developing after both intraventricular hemorrhage and intraventricular infection, with visualization of the precursor via endoscopy and a confirmed glial scar on pathological examination.</AbstractText>Our patient is an preterm-born (at 24 weeks of gestation) male with a grade III intraventricular hemorrhage treated with reservoir placement and serial taps. He did not develop posthemorrhagic hydrocephalus but presented back at approximately 4 months of age with Escherichia coli meningitis that necessitated multiple interventions for intraventricular abscesses, including an endoscopic exploration. He ultimately developed MH requiring placement of a ventriculoperitoneal shunt.</AbstractText>MH is a complex pathology with multiple risk factors. To date, only theories regarding the etiology have been proposed. Our case represents the first known direct visualization of intraventricular fibroglial webbing with magnetic resonance imaging correlation. Improved understanding of the pathophysiology of this entity may improve our ability to treat this pathology before loculations develop.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,837 | Redox states of hemoglobin determine left ventricle pressure recovery and activity of mitochondrial complex IV in hypoxic rat hearts. | Cardiovascular effects were reported to occur in humans and in animal models during transfusion with hemoglobin (Hb)-based oxygen therapeutics. The effects of Hb's iron redox states on cardiac parameters during hypoxia/reoxygenation are however poorly defined. We hypothesize that acute exposures to ferric Hb during hypoxia leads to cardiomyocyte injury and an impaired left ventricular response accompanied by cardiac mitochondrial bioenergetic dysfunction. Recovery of left ventricular functions in an isolated rat heart Langendorff perfusion system was observed following perfusion with ferrous but not with ferric Hb. Ferric Hb induced the development of heart lesions, and impairment of the respiratory chain complex activity. Under normoxia, a sharp decline in cardiac parameters was observed following co-perfusion of low (20 μM) and high (100 μM) ascorbic acid (Asc) with ferrous Hb. This trend continued with ferric Hb co-perfusion, but only at the higher concentration of Asc. These observations suggest that perfusion of the hypoxic heart with ferric Hb increases oxidative stress thereby resulting in cardiac dysfunction. Intervention with Asc to reduce ferric Hb may offer a strategy to control Hb toxicity; however, timing of administration, and dosage of Asc may require individual optimization to target specific redox forms of Hb. |
2,328,838 | Neurenteric cyst of the area postrema causing intractable nausea and vomiting. | Neurenteric cysts are rare, benign congenital lesions of the central nervous system. We present a case of a 59-year-old woman with intractable daily nausea and vomiting with a fourth ventricular cyst adjacent to the area postrema. This was surgically resected leading to complete symptom resolution. |
2,328,839 | Selection of optimal reference genes for gene expression studies in chronically hypoxic rat heart. | Adaptation to chronic hypoxia renders the heart more tolerant to ischemia/reperfusion injury. To evaluate changes in gene expression after adaptation to chronic hypoxia by RT-qPCR, it is essential to select suitable reference genes. In a chronically hypoxic rat model, no specific reference genes have been identified in the myocardium. This study aimed to select the best reference genes in the left (LV) and right (RV) ventricles of chronically hypoxic and normoxic rats. Sprague-Dawley rats were adapted to continuous normobaric hypoxia (CNH; 12% O<sub>2</sub> or 10% O<sub>2</sub>) for 3 weeks. The expression levels of candidate genes were assessed by RT-qPCR. The stability of genes was evaluated by NormFinder, geNorm and BestKeeper algorithms. The best five reference genes in the LV were Top1, Nupl2, Rplp1, Ywhaz, Hprt1 for the milder CNH and Top1, Ywhaz, Sdha, Nupl2, Tomm22 for the stronger CNH. In the RV, the top five genes were Hprt1, Nupl2, Gapdh, Top1, Rplp1 for the milder CNH and Tomm22, Gapdh, Hprt1, Nupl2, Top1 for the stronger CNH. This study provides validation of reference genes in LV and RV of CNH rats and shows that suitable reference genes differ in the two ventricles and depend on experimental protocol. |
2,328,840 | Cardiomyocyte orientation modulated by the Numb family proteins-N-cadherin axis is essential for ventricular wall morphogenesis. | The roles of cellular orientation during trabecular and ventricular wall morphogenesis are unknown, and so are the underlying mechanisms that regulate cellular orientation. Myocardial-specific <i>Numb</i> and <i>Numblike</i> double-knockout (MDKO) hearts display a variety of defects, including in cellular orientation, patterns of mitotic spindle orientation, trabeculation, and ventricular compaction. Furthermore, <i>Numb</i>- and <i>Numblike</i>-null cardiomyocytes exhibit cellular behaviors distinct from those of control cells during trabecular morphogenesis based on single-cell lineage tracing. We investigated how Numb regulates cellular orientation and behaviors and determined that N-cadherin levels and membrane localization are reduced in MDKO hearts. To determine how Numb regulates N-cadherin membrane localization, we generated an mCherry:Numb knockin line and found that Numb localized to diverse endocytic organelles but mainly to the recycling endosome. Consistent with this localization, cardiomyocytes in MDKO did not display defects in N-cadherin internalization but rather in postendocytic recycling to the plasma membrane. Furthermore, N-cadherin overexpression via a mosaic model partially rescued the defects in cellular orientation and trabeculation of MDKO hearts. Our study unravels a phenomenon that cardiomyocytes display spatiotemporal cellular orientation during ventricular wall morphogenesis, and its disruption leads to abnormal trabecular and ventricular wall morphogenesis. Furthermore, we established a mechanism by which Numb modulates cellular orientation and consequently trabecular and ventricular wall morphogenesis by regulating N-cadherin recycling to the plasma membrane. |
2,328,841 | Hydrocephalus Due to Idiopathic Fourth Ventricle Outflow Obstruction. | The fourth ventricle outlet obstruction (FVOO) is a rare but well-established cause of obstructive tetra-ventricular hydrocephalus, characterizing with dilatation or large cerebrospinal fluid collection of the foramina of Magendie and Luschka. In children, it is usually the consequence of posterior cerebral fossa malformations; while in adult, the occlusion is rather acquired than congenital, mostly linked to an inflammatory process, intraventricular hemorrhage, head trauma, brain tumors or Arnold-Chiari malformation. However, idiopathic FVOO is extremely rare, and only 6 such cases have been reported in the English literature. Hereby, we described an extraordinarily rare case of idiopathic FVOO in a 15-year-old patient successfully treated with direct microsurgical excision of the obstruction membrane. Furthermore, the clinical characteristics and treatment for this rare disease were investigated and reviewed. |
2,328,842 | Relative Contributions of Matrix and Myocytes to Biaxial Mechanics of the Right Ventricle in Pulmonary Arterial Hypertension. | Pulmonary arterial hypertension (PAH) commonly leads to right ventricular (RV) hypertrophy and fibrosis that affect the mechanical properties of the RV myocardium (MYO). To investigate the effects of PAH on the mechanics of the RV MYO and extracellular matrix (ECM), we compared RV wall samples, isolated from rats in which PAH was induced using the SuHx protocol, with samples from control animals before and after the tissues were decellularized. Planar biaxial mechanical testing, a technique first adapted to living soft biological tissues by Fung, was performed on intact and decellularized samples. Fung's anisotropic exponential strain energy function fitted the full range of biaxial test results with high fidelity in control and PAH samples both before and after they were decellularized. Mean RV myocardial apex-to-outflow tract and circumferential stresses during equibiaxial strain were significantly greater in PAH than control samples. Mean RV ECM circumferential but not apex-to-outflow tract stresses during equibiaxial strain were significantly greater in the PAH than control group. The ratio of ECM to myocardial stresses at matched strains did not change significantly between groups. Circumferential stresses were significantly higher than apex-to-outflow tract stresses for all groups. These findings confirm the predictions of a mathematical model based on changes in RV hemodynamics and morphology in rat PAH, and may provide a foundation for a new constitutive analysis of the contributions of ECM remodeling to changes in RV filling properties during PAH. |
2,328,843 | DNA methylation reprograms cardiac metabolic gene expression in end-stage human heart failure. | Heart failure (HF) is a leading cause of morbidity and mortality in the United States and worldwide. As a multifactorial syndrome with unpredictable clinical outcomes, identifying the common molecular underpinnings that drive HF pathogenesis remains a major focus of investigation. Disruption of cardiac gene expression has been shown to mediate a common final cascade of pathological hallmarks wherein the heart reactivates numerous developmental pathways. Although the central regulatory mechanisms that drive this cardiac transcriptional reprogramming remain unknown, epigenetic contributions are likely. In the current study, we examined whether the epigenome, specifically DNA methylation, is reprogrammed in HF to potentiate a pathological shift in cardiac gene expression. To accomplish this, we used paired-end whole genome bisulfite sequencing and next-generation RNA sequencing of left ventricle tissue obtained from seven patients with end-stage HF and three nonfailing donor hearts. We found that differential methylation was localized to promoter-associated cytosine-phosphate-guanine islands, which are established regulatory regions of downstream genes. Hypermethylated promoters were associated with genes involved in oxidative metabolism, whereas promoter hypomethylation enriched glycolytic pathways. Overexpression of plasmid-derived DNA methyltransferase 3A in vitro was sufficient to lower the expression of numerous oxidative metabolic genes in H9c2 rat cardiomyoblasts, further supporting the importance of epigenetic factors in the regulation of cardiac metabolism. Last, we identified binding-site competition via hypermethylation of the nuclear respiratory factor 1 (NRF1) motif, an established upstream regulator of mitochondrial biogenesis. These preliminary observations are the first to uncover an etiology-independent shift in cardiac DNA methylation that corresponds with altered metabolic gene expression in HF.<b>NEW & NOTEWORTHY</b> The failing heart undergoes profound metabolic changes because of alterations in cardiac gene expression, reactivating glycolytic genes and suppressing oxidative metabolic genes. In the current study, we discover that alterations to cardiac DNA methylation encode this fetal-like metabolic gene reprogramming. We also identify novel epigenetic interference of nuclear respiratory factor 1 via hypermethylation of its downstream promoter targets, further supporting a novel contribution of DNA methylation in the metabolic remodeling of heart failure. |
2,328,844 | Histopathological and Morphometric Study of Fibrosis and Nuclear Pleomorphism in Dilated Cardiomyopathy. | Histopathological changes associated with dilated cardiomyopathy (CMD) are frequently nonspecific and often only present in the terminal stage of the disease. The study followed the histopathological and morphometric quantification of fibrosis and nuclear pleomorphism in CMD. We analyzed left ventricle myocardial fragments harvested during autopsy, from 35 cases with clinical diagnosis of CMD and 5 cases of normal myocardium. Fibrosis was present in all CMD cases, with higher values compared with control cases. Nuclear pleomorphism was identified in 18 cases (45%), two of the analyzed parameters, respectively the ratio of nuclear diameters and roundness of nucleus, revealing significant differences in CMD compared to the control cases. Myocardial fibrosis present in all cases of CMD represents a major feature of the disease. The nuclear pleomorphism due to the nuclei change in diameters and size was more pronounced in the vicinity of fibrosis areas, possibly related to this alteration. |
2,328,845 | MRI coupled with clinically-applicable iron oxide nanoparticles reveals choroid plexus involvement in a murine model of neuroinflammation. | Choroid plexus (ChPs) are involved in the early inflammatory response that occurs in many brain disorders. However, the activation of immune cells within the ChPs in response to neuroinflammation is still largely unexplored in-vivo. There is therefore a crucial need for developing imaging tool that would allow the non-invasive monitoring of ChP involvement in these diseases. Magnetic resonance imaging (MRI) coupled with superparamagnetic particles of iron oxide (SPIO) is a minimally invasive technique allowing to track phagocytic cells in inflammatory diseases. Our aim was to investigate the potential of ultrasmall SPIO (USPIO)-enhanced MRI to monitor ChP involvement in-vivo in a mouse model of neuroinflammation obtained by intraperitoneal administration of lipopolysaccharide. Using high resolution MRI, we identified marked USPIO-related signal drops in the ChPs of animals with neuroinflammation compared to controls. We confirmed these results quantitatively using a 4-points grading system. Ex-vivo analysis confirmed USPIO accumulation within the ChP stroma and their uptake by immune cells. We validated the translational potential of our approach using the clinically-applicable USPIO Ferumoxytol. MR imaging of USPIO accumulation within the ChPs may serve as an imaging biomarker to study ChP involvement in neuroinflammatory disorders that could be applied in a straightforward way in clinical practice. |
2,328,846 | Opposite Effects of Voluntary Physical Exercise on β3-Adrenergic Receptors in the White and Brown Adipose Tissue. | Catecholamine effects via β3-adrenergic receptors are important for the metabolism of the adipose tissue. Physical exercise is a core component of antiobesity regimens. We have tested the hypothesis that voluntary wheel running results in enhancement of β3-adrenergic receptor gene expression in the white and brown adipose tissues. The secondary hypothesis is that dietary tryptophan depletion modifies metabolic effects of exercise. Male Sprague-Dawley rats were assigned for sedentary and exercise groups with free access to running wheels for 3 weeks. All animals received normal control diet for 7 days. Both groups were fed either by low tryptophan (0.04%) diet or by control diet (0.2%) for next 2 weeks. The β3-adrenergic receptor mRNA levels in response to running increased in the retroperitoneal and epididymal fat pads. The gene expression of uncoupling protein-1 (UCP-1) was increased in the brown, while unchanged in the white fat tissues. Unlike control animals, the rats fed by low tryptophan diet did not exhibit a reduction of the white adipose tissue mass. Tryptophan depletion resulted in enhanced concentrations of plasma aldosterone and corticosterone, but had no influence on exercise-induced adrenal hypertrophy. No changes in β3-adrenergic receptor and cell proliferation measured by 5-bromo-2'-deoxyuridine incorporation in left heart ventricle were observed. The reduced β3-adrenergic receptor but not enhanced uncoupling protein-1 gene expression supports the hypothesis on hypoactive brown adipose tissue during exercise. Reduction in dietary tryptophan had no major influence on the exercise-induced changes in the metabolic parameters measured. |
2,328,847 | Incipient Transcalvarial Cerebral Herniation: Underrecognized Complication of Elective Craniotomy. | Herniation of the brain through an osseodural defect has been well described in small children as an uncommon occurrence after closed head injury. Pressure from the growing brain has been implicated in progressive enlargement and reshaping of the fracture line. An analogous phenomenon in adults has been observed in the described cases where neurosurgical intervention led to a persistent dural defect. Transcalvarial herniation of the brain through the dural defect resulted in characteristic neurologic and imaging findings producing symptoms disproportionately greater than expected from the extent of the affected brain, accompanied by enlargement of the underlying ventricle and elevation of the bone flap. Disruption of the axonal conduction due to distortion of the axons in the herniated brain is probably responsible for these observations.</AbstractText>A series of 3 cases is described. In all cases, the dural reconstitution at the conclusion of surgery was incomplete. Brain herniation was evident in the postoperative scan. The transcalvarial herniation of the brain was precipitated by either a seizure and resultant brain swelling or persistently raised intracranial tension from a tumor residual. In 2 cases, surgical reexploration resulted in improvement in the neurologic symptoms.</AbstractText>In symptomatic patients with transcalvarial herniation of the brain, identified on imaging, the neurologic syndrome is quite characteristic. Recognition of this condition and prompt treatment lead to lasting neurologic improvement.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,848 | Slit Ventricle as a Neurosurgical Emergency: Case Report and Review of Literature. | Symptomatic slit ventricle is one of the most challenging complications of shunt surgery in children. Clinical signs and symptoms may appear with a wide range of intracranial pressure (ICP) values. We report the case of a 10-year-old girl, who did not present the classic clinical features of extremely elevated ICP, which was proven by multiple invasive ICP recordings, performed during shunt revisions.</AbstractText>At the age of 6 months, the patient presented squeal for many hours, accompanied with sunset eyes, bulging anterior fontanel, and dilated ventricles of all 4 ventricles on computed tomography scan. Acute ventriculoperitoneal shunt insertion was performed with adjustable valve. During the following 9 years, she was regularly seen and medically treated for intermittent headache, with nausea and vomiting. From 9 years of age, she was hospitalized for severe (10/10 on the visual analog scale), unbearable headache, agitation, and screaming on multiple occasions. Altogether, we had to revise the shunt system 5 times throughout 1 year. Radiologic imaging always showed narrow ventricles. Ophthalmologic examination of the fundus never revealed signs of raised ICP. Perioperative monitoring of the ICP with intraparenchymal sensor showed unexpected high values of 40-45 mm Hg. However, repetitive shunt revisions were successful only temporarily because the symptoms always returned. Only bilateral shunting of the ventricular system was able to eliminate the symptoms permanently.</AbstractText>Images of slit ventricle can be associated either with low or extremely high ICP needing urgent surgical consideration, including ICP monitoring. Bilateral shunt insertion can be effective treatment for slit ventricle syndrome.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,849 | Method for Calibration of Left Ventricle Material Properties Using Three-Dimensional Echocardiography Endocardial Strains. | We sought to calibrate mechanical properties of left ventricle (LV) based on three-dimensional (3D) speckle tracking echocardiographic imaging data recorded from 16 segments defined by American Heart Association (AHA). The in vivo data were used to create finite element (FE) LV and biventricular (BV) models. The orientation of the fibers in the LV model was rule based, but diffusion tensor magnetic resonance imaging (MRI) data were used for the fiber directions in the BV model. A nonlinear fiber-reinforced constitutive equation was used to describe the passive behavior of the myocardium, whereas the active tension was described by a model based on tissue contraction (Tmax). isight was used for optimization, which used abaqus as the forward solver (Simulia, Providence, RI). The calibration of passive properties based on the end diastolic pressure volume relation (EDPVR) curve resulted in relatively good agreement (mean error = -0.04 ml). The difference between the experimental and computational strains decreased after segmental strain metrics, rather than global metrics, were used for calibration: for the LV model, the mean difference reduced from 0.129 to 0.046 (circumferential) and from 0.076 to 0.059 (longitudinal); for the BV model, the mean difference nearly did not change in the circumferential direction (0.061) but reduced in the longitudinal direction from 0.076 to 0.055. The calibration of mechanical properties for myocardium can be improved using segmental strain metrics. The importance of realistic fiber orientation and geometry for modeling of the LV was shown. |
2,328,850 | Tanycytes and the Control of Thyrotropin-Releasing Hormone Flux Into Portal Capillaries. | Central and peripheral mechanisms that modulate energy intake, partition and expenditure determine energy homeostasis. Thyroid hormones (TH) regulate energy expenditure through the control of basal metabolic rate and thermogenesis; they also modulate food intake. TH concentrations are regulated by the hypothalamus-pituitary-thyroid (HPT) axis, and by transport and metabolism in blood and target tissues. In mammals, hypophysiotropic thyrotropin-releasing hormone (TRH) neurons of the paraventricular nucleus of the hypothalamus integrate energy-related information. They project to the external zone of the median eminence (ME), a brain circumventricular organ rich in neuron terminal varicosities and buttons, tanycytes, other glial cells and capillaries. These capillary vessels form a portal system that links the base of the hypothalamus with the anterior pituitary. Tanycytes of the medio-basal hypothalamus express a repertoire of proteins involved in transport, sensing, and metabolism of TH; among them is type 2 deiodinase, a source of 3,3',5-triiodo-L-thyronine necessary for negative feedback on TRH neurons. Tanycytes subtypes are distinguished by position and phenotype. The end-feet of β2-tanycytes intermingle with TRH varicosities and terminals in the external layer of the ME and terminate close to the ME capillaries. Besides type 2 deiodinase, β2-tanycytes express the TRH-degrading ectoenzyme (TRH-DE); this enzyme likely controls the amount of TRH entering portal vessels. TRH-DE is rapidly upregulated by TH, contributing to TH negative feedback on HPT axis. Alterations in energy balance also regulate the expression and activity of TRH-DE in the ME, making β2-tanycytes a hub for energy-related regulation of HPT axis activity. β2-tanycytes also express TRH-R1, which mediates positive effects of TRH on TRH-DE activity and the size of β2-tanycyte end-feet contacts with the basal lamina adjacent to ME capillaries. These end-feet associations with ME capillaries, and TRH-DE activity, appear to coordinately control HPT axis activity. Thus, down-stream of neuronal control of TRH release by action potentials arrival in the external layer of the median eminence, imbricated intercellular processes may coordinate the flux of TRH into the portal capillaries. In conclusion, β2-tanycytes appear as a critical cellular element for the somatic and post-secretory control of TRH flux into portal vessels, and HPT axis regulation in mammals. |
2,328,851 | A Protocol for Transverse Cardiac Slicing and Optical Mapping in Murine Heart. | Thin living tissue slices have recently emerged as a new tissue model for cardiac electrophysiological research. Slices can be produced from human cardiac tissue, in addition to small and large mammalian hearts, representing a powerful <i>in vitro</i> model system for preclinical and translational heart research. In the present protocol, we describe a detailed mouse heart transverse slicing and optical imaging methodology. The use of this technology for high-throughput optical imaging allows study of electrophysiology of murine hearts in an organotypic pseudo two-dimensional model. The slices are cut at right angles to the long axis of the heart, permitting robust interrogation of transmembrane potential (V<sub>m</sub>) and calcium transients (CaT) throughout the entire heart with exceptional regional precision. This approach enables the use of a series of slices prepared from the ventricles to measure V<sub>m</sub> and CaT with high temporal and spatial resolution, allowing (i) comparison of successive slices which form a stack representing the original geometry of the heart; (ii) profiling of transmural and regional gradients in V<sub>m</sub> and CaT in the ventricle; (iii) characterization of transmural and regional profiles of action potential and CaT alternans under stress (e.g., high frequency pacing or β-adrenergic stimulation) or pathological conditions (e.g., hypertrophy). Thus, the protocol described here provides a powerful platform for innovative research on electrical and calcium handling heterogeneity within the heart. It can be also combined with optogenetic technology to carry out optical stimulation; aiding studies of cellular V<sub>m</sub> and CaT in a cell type specific manner. |
2,328,852 | Neural signatures of sleep in zebrafish. | Slow-wave sleep and rapid eye movement (or paradoxical) sleep have been found in mammals, birds and lizards, but it is unclear whether these neuronal signatures are found in non-amniotic vertebrates. Here we develop non-invasive fluorescence-based polysomnography for zebrafish, and show-using unbiased, brain-wide activity recording coupled with assessment of eye movement, muscle dynamics and heart rate-that there are at least two major sleep signatures in zebrafish. These signatures, which we term slow bursting sleep and propagating wave sleep, share commonalities with those of slow-wave sleep and paradoxical or rapid eye movement sleep, respectively. Further, we find that melanin-concentrating hormone signalling (which is involved in mammalian sleep) also regulates propagating wave sleep signatures and the overall amount of sleep in zebrafish, probably via activation of ependymal cells. These observations suggest that common neural signatures of sleep may have emerged in the vertebrate brain over 450 million years ago. |
2,328,853 | Practical tips and tricks in measuring strain, strain rate and twist for the left and right ventricles. | Strain imaging provides an accessible, feasible and non-invasive technique to assess cardiac mechanics. Speckle tracking echocardiography (STE) is the primary modality with the utility for detection of subclinical ventricular dysfunction. Investigation and adoption of this technique has increased significantly in both the research and clinical environment. It is therefore important to provide information to guide the sonographer on the production of valid and reproducible data. The focus of this review is to (1) describe cardiac physiology and mechanics relevant to strain imaging, (2) discuss the concepts of strain imaging and STE and (3) provide a practical guide for the investigation and interpretation of cardiac mechanics using STE. |
2,328,854 | Persistence of right ventricular dysfunction and altered morphometry in asymptomatic preterm Infants through one year of age: Cardiac phenotype of prematurity. | Prematurity impacts myocardial development and may determine long-term outcomes. The objective of this study was to test the hypothesis that preterm neonates develop right ventricle dysfunction and adaptive remodelling by 32 weeks post-menstrual age that persists through 1 year corrected age.</AbstractText>A subset of 80 preterm infants (born <29 weeks) was selected retrospectively from a prospectively enrolled cohort and measures of right ventricle systolic function and morphology by two-dimensional echocardiography were assessed at 32 weeks post-menstrual age and at 1 year of corrected age. Comparisons were made to 50 term infants at 1 month and 1 year of age. Sub-analyses were performed in preterm-born infants with bronchopulmonary dysplasia and/or pulmonary hypertension.</AbstractText>In both term and preterm infants, right ventricle function and morphology increased over the first year (p < 0.01). The magnitudes of right ventricle function measures were lower in preterm-born infants at each time period (p < 0.01 for all) and right ventricle morphology indices were wider in all preterm infants by 1 year corrected age, irrespective of lung disease. Measures of a) right ventricle function were further decreased and b) morphology increased through 1 year in preterm infants with bronchopulmonary dysplasia and/or pulmonary hypertension (p < 0.01).</AbstractText>Preterm infants exhibit abnormal right ventricle performance with remodelling at 32 weeks post-menstrual age that persists through 1 year corrected age, suggesting a less developed intrinsic myocardial function response following preterm birth. The development of bronchopulmonary dysplasia and pulmonary hypertension leave a further negative impact on right ventricle mechanics over the first year of age.</AbstractText> |
2,328,855 | Normal-pressure hydrocephalus: A critical review. | Normal-pressure hydrocephalus (NPH) is a potentially reversible syndrome characterized by enlarged cerebral ventricles (ventriculomegaly), cognitive impairment, gait apraxia and urinary incontinence. A critical review of the concept, pathophysiology, diagnosis, and treatment of both idiopathic and secondary NPH was conducted. We searched Medline and PubMed databases from January 2012 to December 2018 using the keywords "normal-pressure hydrocephalus" / "idiopathic normal-pressure hydrocephalus" / "secondary normal-pressure hydrocephalus" / "NPH" / "ventriculoperitoneal shunt". The initial search produced 341 hits. After careful selection, a total of 54 articles were chosen and additional relevant studies were included during the process of writing this article. NPH is an important cause of potentially reversible dementia, frequent falls and recurrent urinary infections in the elderly. The clinical and imaging features of NPH may be incomplete or nonspecific, posing a diagnostic challenge for medical doctors and often requiring expert assessment to minimize unsuccessful surgical treatments. Recent advances resulting from the use of non-invasive MRI methods for quantifying cerebral blood flow, in particular arterial spin-labeling (ASL), and the frequent association of NPH and obstructive sleep apnea (OSA), offer new avenues to understand and treat NPH.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Oliveira</LastName><ForeName>Louise Makarem</ForeName><Initials>LM</Initials><AffiliationInfo><Affiliation>Medical Student, School of Medicine, Federal University of Amazonas (UFAM), Manaus, AM, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nitrini</LastName><ForeName>Ricardo</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Professor of Neurology, Department of Neurology, University of São Paulo Medical School, São Paulo, SP, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Román</LastName><ForeName>Gustavo C</ForeName><Initials>GC</Initials><AffiliationInfo><Affiliation>The Jack S. Blanton Distinguished Endowed Chair, Neurological Institute Houston, Methodist Hospital, Professor of Neurology Weill Cornell Medical College Methodist Neurological Institute, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Brazil</Country><MedlineTA>Dement Neuropsychol</MedlineTA><NlmUniqueID>101506587</NlmUniqueID><ISSNLinking>1980-5764</ISSNLinking></MedlineJournalInfo><CommentsCorrectionsList><CommentsCorrections RefType="ErratumIn"><RefSource>Dement Neuropsychol. 2019 Jul-Sep;13(3):361</RefSource><PMID Version="1">31555412</PMID></CommentsCorrections></CommentsCorrectionsList><OtherAbstract Type="Publisher" Language="por">A hidrocefalia de pressão normal (HPN) é uma síndrome potencialmente reversível marcada por ventrículos cerebrais alargados (ventriculomegalia), declínio cognitivo, apraxia da marcha e incontinência urinária. Revisar criticamente o conceito, a fisiopatologia, o diagnóstico e o tratamento da HPN idiopática e secundária. Os autores acessaram as bases de dados Medline e Pubmed entre janeiro de 2012 e dezembro de 2018, utilizando as palavras-chave <i>“normal-pressure hydrocephalus” / “idiopathic normal-pressure hydrocephalus” / “secondary normal-pressure hydrocephalus”</i> / “NPH” / <i>“ventriculoperitoneal shunt”</i>. A busca inicial resultou em 341 artigos. Após cuidadosa seleção, 54 estudos foram escolhidos e pesquisas adicionais foram incluídas durante o processo de elaboração do manuscrito. A HPN é uma importante causa de demência potencialmente reversível, quedas frequentes e infecção urinária recorrente em idosos. As características clínicas e de imagem da HPN podem ser incompletas ou inespecíficas, de modo que este se torna um diagnóstico difícil para médicos. Não raro uma avaliação por especialista é necessária, visando minimizar tratamentos cirúrgicos ineficazes. Avanços recentes advindos do uso não invasivo de ressonância magnética para quantificação do fluxo sanguíneo cerebral, em particular <i>arterial spin-labeling</i> (ASL), assim como a usual associação entre HPN e apneia obstrutiva do sono representam novos meios de entender e de tratar a HPN. |
2,328,856 | Cumulative gadodiamide administration leads to brain gadolinium deposition in early MS. | Frequent administration of gadolinium-based contrast agents in multiple sclerosis (MS) may increase signal intensity (SI) unenhanced T1-weighted imaging MRI throughout the brain. We evaluated the association between lifetime cumulative doses of gadodiamide administration and increased SI within the dentate nucleus (DN), globus pallidus (GP), and thalamus in patients with early MS.</AbstractText>A total of 203 patients with MS (107 with baseline and follow-up MRI assessments) and 262 age- and sex-matched controls were included in this retrospective, longitudinal, 3T MRI-reader-blinded study. Patients with MS had disease duration <2 years at baseline and received exclusively gadodiamide at all MRI time points. SI ratio (SIR) to pons and CSF of lateral ventricle volume (CSF-LVV) were assessed. Analysis of covariance and correlation analyses, adjusted for age, sex, and region of interest volume, were used.</AbstractText>The mean follow-up time was 55.4 months, and the mean number of gadolinium-based contrast agents administrations was 9.2. At follow-up, 49.3% of patients with MS and no controls showed DN T1 hyperintensity (p</i> < 0.001). The mean SIR of DN (p</i> < 0.001) and of GP (p</i> = 0.005) to pons and the mean SIR of DN, GP, and thalamus to CSF-LVV were higher in patients with MS compared to controls (p</i> < 0.001). SIR of DN to pons was associated with number of gadodiamide doses (p</i> < 0.001). No associations between SIR of DN, GP, and thalamus and clinical and MRI outcomes of disease severity were detected over the follow-up.</AbstractText>DN, GP, and thalamus gadolinium deposition in early MS is associated with lifetime cumulative gadodiamide administration without clinical or radiologic correlates of more aggressive disease.</AbstractText>© 2019 American Academy of Neurology.</CopyrightInformation> |
2,328,857 | Monitoring Cell-Type-Specific Gene Expression Using Ribosome Profiling In Vivo During Cardiac Hemodynamic Stress. | Gene expression profiles have been mainly determined by analysis of transcript abundance. However, these analyses cannot capture posttranscriptional gene expression control at the level of translation, which is a key step in the regulation of gene expression, as evidenced by the fact that transcript levels often poorly correlate with protein levels. Furthermore, genome-wide transcript profiling of distinct cell types is challenging due to the fact that lysates from tissues always represent a mixture of cells.</AbstractText>This study aimed to develop a new experimental method that overcomes both limitations and to apply this method to perform a genome-wide analysis of gene expression on the translational level in response to pressure overload.</AbstractText>By combining ribosome profiling (Ribo-seq) with a ribosome-tagging approach (Ribo-tag), it was possible to determine the translated transcriptome in specific cell types from the heart. After pressure overload, we monitored the cardiac myocyte translatome by purifying tagged cardiac myocyte ribosomes from cardiac lysates and subjecting the ribosome-protected mRNA fragments to deep sequencing. We identified subsets of mRNAs that are regulated at the translational level and found that translational control determines early changes in gene expression in response to cardiac stress in cardiac myocytes. Translationally controlled transcripts are associated with specific biological processes related to translation, protein quality control, and metabolism. Mechanistically, Ribo-seq allowed for the identification of upstream open reading frames in transcripts, which we predict to be important regulators of translation.</AbstractText>This method has the potential to (1) provide a new tool for studying cell-specific gene expression at the level of translation in tissues, (2) reveal new therapeutic targets to prevent cellular remodeling, and (3) trigger follow-up studies that address both, the molecular mechanisms involved in the posttranscriptional control of gene expression in cardiac cells, and the protective functions of proteins expressed in response to cellular stress.</AbstractText> |
2,328,858 | EVCMR: A tool for the quantitative evaluation and visualization of cardiac MRI data. | Quantitative evaluation of diseased myocardium in cardiac magnetic resonance imaging (MRI) plays an important role in the diagnosis and prognosis of cardiovascular disease. The development of a user interface with state-of-the-art techniques would be beneficial for the efficient post-processing and analysis of cardiac images. The aim of this study was to develop a custom user interface tool for the quantitative evaluation of the short-axis left ventricle (LV) and myocardium. Modules for cine, perfusion, late gadolinium enhancement (LGE), and T1 mapping data analyses were developed in Python, and a module for three-dimensional (3D) visualization was implemented using PyQtGraph library. The U-net segmentation and manual contour correction in the user interface were effective in generating reference myocardial segmentation masks, which helped obtain labeled data for deep learning model training. The proposed U-net segmentation resulted in a mean Dice score of 0.87 (±0.02) in cine diastolic myocardial segmentation. The LV mass measurement of the proposed method showed good agreement with that of manual segmentation (intraclass correlation coefficient = 0.97, mean difference and 95% Bland-Altman limits of agreement = 4.4 ± 12.2 g). C++ implementation of voxel-wise T1 mapping and its binding via pybind11 led to a significant computational gain in calculating the T1 maps. The 3D visualization enabled fast user interactions in rotating and zooming-in/out of the 3D myocardium and scar transmurality. The custom tool has the potential to provide a fast and comprehensive analysis of the LV and myocardium from multi-parametric MRI data in clinical settings. |
2,328,859 | Cardiovascular and hidroelectrolytic changes in rats fed with high-fat diet. | Obesity activates the renin-angiotensin and sympathetic systems facilitating hypertension and changes in the hydroelectrolytic balance. In the present study, in rats fed with high-fat diet (HFD), we investigated daily water intake and urinary excretion, prandial consumption of water and the changes in blood pressure and water intake to intracerebroventricular (icv) angiotensin II (ANG II). Male Holtzman rats (290-320 g) were fed with standard diet (SD, 11% calories from fat) or HFD (45% calories from fat) for 6 weeks. Part of the animals received a stainless steel cannula in the lateral ventricle (LV) at the 6th week after the beginning of the diets and the experiments were performed at the 7th week. The pressor effect, but not the dipsogenic response to acute icv injection of ANG II, was potentiated in the HFD rats. Daily water intake and urinary volume were reduced in rats fed with HFD with no significant changes in sodium excretion. Prandial water consumption was also reduced in rats ingesting HFD, an effect almost totally reverted blocking salivation with atropine. These results show a potentiation of the pressor response to icv ANG II in HFD-fed rats, without changing icv ANG II-induced water intake. In addition, prandial and daily water intake and urinary volume were reduced in HFD-fed rats, without changing sodium excretion. Salivation in rats ingesting HFD may play a role in the reduced prandial and daily water intake. |
2,328,860 | Biological Indices Evaluation of Various Treatment Techniques for Left-Sided Breast Treatment. | To compare dose to organs at risk (OARs) and biological evaluation using normal tissue complication probability (NTCP) for left-sided breast radiation therapy in 4 techniques: supine free breathing (SFB), supine deep inspiration breath hold (SDIBH), prone free breathing (PFB), and prone deep inspiration breath hold (PDIBH).</AbstractText>Twenty-five patients with left-sided breast cancer suitable for this study underwent a computed tomography scan using SFB, SDIBH, PFB, and PDIBH. One radiation oncologist contoured the planning target volume and OAR (cardiac components). Dose-volume histograms and NTCPs for the heart, left ventricle (LV), left anterior descending artery (LAD), and left lung were calculated for all 4 techniques.</AbstractText>The mean heart dose in PDIBH is 0.77 Gy, which is statistically significantly lower than in SFB (1.88 Gy, P < .0001), SDIBH (0.97 Gy, P < .001), and PFB (0.85 Gy, P < .001). The mean left lung dose is 0.69 Gy in PFB and 0.88 Gy in PDIBH. PFB and PDIBH have statistically significantly lower doses compared with SFB (6.09 Gy, P < .0001) and SDIBH (5.41 Gy, P < .0001). The mean NTCP in SFB for the heart, LV, and LAD is 0.27%, 0.62%, and 4.23%, respectively, and it is negligible for other techniques.</AbstractText>We found that PDIBH had a dosimetrically lower mean dose for the heart and LV compared with the other 3 techniques. In addition, SDIBH, PFB and PDIBH had statistically significantly lower NTCP for the heart, LV, and LAD compared with SFB. NTCP for the left lung was statistically significantly lower for prone techniques compared with supine techniques. Therefore we concluded that, compared with SDIBH, PDIBH provides the added benefit of sparing the heart while keeping the benefit of sparing the lung as in the prone technique.</AbstractText>Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,861 | The non-steroidal mineralocorticoid receptor antagonist finerenone prevents cardiac fibrotic remodeling. | Mineralocorticoid receptor (MR) overactivation promotes cardiac fibrosis. We studied the ability of the non-steroidal MR antagonist finerenone to prevent fibrotic remodeling. In neonatal rat cardiac fibroblasts, finerenone prevented aldosterone-induced nuclear MR translocation. Treatment with finerenone decreased the expression of connective tissue growth factor (CTGF) (74 ± 15% of control, p = 0.005) and prevented aldosterone-induced upregulation of CTGF and lysyl oxidase (LOX) completely. Finerenone attenuated the upregulation of transforming growth factor ß (TGF-ß), which was induced by the Rac1 GTPase activator l-buthionine sulfoximine. Transgenic mice with cardiac-specific overexpression of Rac1 (RacET) showed increased left ventricular (LV) end-diastolic (63.7 ± 8.0 vs. 93.8 ± 25.6 µl, p = 0.027) and end-systolic (28.0 ± 4.0 vs. 49.5 ± 16.7 µl, p = 0.014) volumes compared to wild-type FVBN control mice. Treatment of RacET mice with 100 ppm finerenone over 5 months prevented LV dilatation. Systolic and diastolic LV function did not differ between the three groups. RacET mice exhibited overactivation of MR and 11ß hydroxysteroid dehydrogenase type 2. Both effects were reduced by finerenone (reduction about 36%, p = 0.030, and 40%, p = 0.032, respectively). RacET mice demonstrated overexpression of TGF-ß, CTGF, LOX, osteopontin as well as collagen and myocardial fibrosis in the left ventricle. In contrast, expression of these parameters did not differ between finerenone-treated RacET and control mice. Finerenone prevented left atrial dilatation (6.4 ± 1.5 vs. 4.7 ± 1.4 mg, p = 0.004) and left atrial fibrosis (17.8 ± 3.1 vs. 12.8 ± 3.1%, p = 0.046) compared to vehicle-treated RacET mice. In summary, finerenone prevented from MR-mediated structural remodeling in cardiac fibroblasts and in RacET mice. These data demonstrate anti-fibrotic myocardial effects of finerenone. |
2,328,862 | Ultrasound Measurements of Frontal Horns and the Cavum Septi Pellucidi in Healthy Fetuses in the Second and Third Trimesters of Pregnancy. | To assess the visualization rate and size of the frontal horns (FHs) and cavum septi pellucidi (CSP) in healthy fetuses throughout pregnancy.</AbstractText>After Institutional Review Board approval, 522 consecutive uncomplicated singleton pregnancies between 15 and 39 gestational weeks were enrolled in the study. Ultrasound measurements of the anterior horn width (AHW), center from the horn distance (CFHD), distance from the FHs to the CSP, and CSP width were retrospectively performed using axial transventricular or transcerebellar planes. Available maternal body mass indices were recorded.</AbstractText>At least 1 FH was seen in 78% of the cases. The mean AHW decreased over the second trimester and plateaued in the third trimester. The CFHD plateaued in the second trimester and increased in the third trimester. Downside FHs were generally larger than upside FHs. More FHs were measured in transventricular (69%) than transcerebellar (31%) planes. Frontal horns were seen with high, low, and no confidence in 57%, 21%, and 22% of cases, respectively. No-confidence rates were 17% in the second trimester and 42% in the third trimester. The CSP was not visualized in 4% of cases; 15 of 19 cases of a nonvisualized CSP were scanned between 18 and 37 weeks. Mean body mass indices ± SDs were 27.6 ± 6.7 kg/m2</sup> for the patients in cases of a visualized CSP and 32.4 ± 9.1 kg/m2</sup> for the patients in cases of a nonvisualized CSP.</AbstractText>Normative data for the fetal FH and CSP width were established. Frontal horns are more frequently seen on transventricular views and are difficult to confidently assess in the late third trimester. This study challenges previously reported data that the CSP is seen in 100% of cases from 18 to 37 weeks.</AbstractText>© 2019 by the American Institute of Ultrasound in Medicine.</CopyrightInformation> |
2,328,863 | Evaluation of Myelin Radiotracers in the Lysolecithin Rat Model of Focal Demyelination: Beware of Pitfalls! | The observation that amyloid radiotracers developed for Alzheimer's disease bind to cerebral white matter paved the road to nuclear imaging of myelin in multiple sclerosis. The lysolecithin (lysophosphatidylcholine (LPC)) rat model of demyelination proved useful in evaluating and comparing candidate radiotracers to target myelin. Focal demyelination following stereotaxic LPC injection is larger than lesions observed in experimental autoimmune encephalitis models and is followed by spontaneous progressive remyelination. Moreover, the contralateral hemisphere may serve as an internal control in a given animal. However, demyelination can be accompanied by concurrent focal necrosis and/or adjacent ventricle dilation. The influence of these side effects on imaging findings has never been carefully assessed. The present study describes an optimization of the LPC model and highlights the use of MRI for controlling the variability and pitfalls of the model. The prototypical amyloid radiotracer [<sup>11</sup>C]PIB was used to show that <i>in vivo</i> PET does not provide sufficient sensitivity to reliably track myelin changes and may be sensitive to LPC side effects instead of demyelination as such. <i>Ex vivo</i> autoradiography with a fluorine radiotracer should be preferred, to adequately evaluate and compare radiotracers for the assessment of myelin content. |
2,328,864 | Resolvin D1 Attenuates Myocardial Infarction in a Rodent Model with the Participation of the HMGB1 Pathway. | Myocardial infarction (MI) is associated with high morbidity and mortality worldwide. This study aimed to explore the roles of resolvin D1 (RvD1), a metabolite of omega-3 polyunsaturated fatty acids, in protection against MI and investigate its influences on high mobility group box 1 protein (HMGB1) and related molecular mechanisms.</AbstractText>Three-month-old male Sprague-Dawley rats were divided into five groups: sham, MI, MI+0.02 μg RvD1, MI+0.1 μg RvD1, and MI+0.3 μg RvD1. Vehicle control or different doses of RvD1 were injected into the left ventricle (LV) cavity 5 min before MI induction. During MI induction, myocardial ischemia lasted for 45 min followed by 180 min of reperfusion. After the reperfusion, blood and LV samples were collected for biochemical examination.</AbstractText>The MI group produced a significant increase in myocardial infarct size, serum cardiac biomarkers (LDH and CK-MB), proinflammatory cytokines (TNF-α and IL-6), and MDA levels, and a significant decrease in SOD level compared with the sham group. Moreover, a significant upregulation of gene and protein expressions of HMGB1 and its related TLR4 and NF-κB were observed in the MI group when compared with the sham group. Pretreatment of RvD1 ameliorated the biochemical changes caused by MI.</AbstractText>Our results suggested that RvD1 pretreatment exhibited protective effects against MI through downregulation of HMGB1 and its related TLR4 and NF-κB expressions.</AbstractText> |
2,328,865 | The cardioprotective effects of diallyl trisulfide on diabetic rats with ex vivo induced ischemia/reperfusion injury. | Diallyl trisulfide (DATS) is distinguished as the most potent polysulfide isolated from garlic. The aim of our study was to investigate effects of oral administration of DATS on healthy and diabetic rats, with special attention on heart function. Rats were randomly divided into four groups: CTRL (healthy rats), DATS (healthy rats treated with DATS), DM (diabetic rats), DM + DATS (diabetic rats treated with DATS). DATS (40 mg/kg of body weight) was administered every other day for 3 weeks, at the end of which rats underwent echocardiography, glycemic measurement and redox status assessment. Isolated rat hearts were subjected to 30 min global ischemia and 60 min reperfusion, after which heart tissue was counterstain with hematoxylin and eosin and cardiac Troponin T staining (cTnT), while expression of Bax, B cell lymphoma 2 (Bcl-2), caspase-3, caspase-9 and superoxide dismutase-2 were examined in the left ventricle. DATS treatment significantly reduced blood glucose levels of diabetic rats, and improved cardiac function recovery, diminished oxidation status, attenuated cardiac remodeling and inhibited myocardial apoptosis in healthy and diabetic rats. DATS treatment causes promising cardioprotective effects on ex vivo-induced ischemia/reperfusion (I/R) injury in diabetic and healthy rat heart probably mediated by inhibited myocardial apoptosis. Moreover, appropriate DATS consumption may provide potential co-therapy or prevention of hyperglycemia and various cardiac complications in rats with DM. |
2,328,866 | Differential coupling between subcortical calcium and BOLD signals during evoked and resting state through simultaneous calcium fiber photometry and fMRI. | Task based and resting state fMRI has been widely utilized to study brain functions. As the foundation of fMRI, the underlying neural basis of the BOLD signal has been extensively studied, but the detailed mechanism remains elusive, particularly during the resting state. To examine the neurovascular coupling, it is important to simultaneously record neural and vascular signals. Here we developed a novel setup of camera based, scalable simultaneous calcium fiber photometry and fMRI in rats. Using this setup, we recorded calcium signals of superior colliculus (SC) and lateral geniculate nucleus (LGN) and fMRI simultaneously during visual stimulation and the resting state. Our results revealed robust, region-specific coupling between calcium and BOLD signals in the task state and weaker, whole brain correlation in the resting state. Interestingly, the spatial specificity of such correlation in the resting state was improved upon regression of white matter, ventricle signals and global signals in fMRI data. Overall, our results suggest differential coupling of calcium and BOLD signals for subcortical regions between evoked and resting states, and the coupling relationship in the resting state was related with resting state BOLD preprocessing strategies. |
2,328,867 | Fetal MRI in Prenatal Diagnosis of Encephalocele. | Encephalocele, a rare congenital brain malformation, is herniation of brain tissue with or without meninges through a cranial fossa defect. It is classified by location and is usually associated with other congenital anomalies.</AbstractText>A 29-year-old G2, P1, 36-week pregnant woman was referred for fetal ultrasound delivery planning. Sonographic abnormalities led to fetal magnetic resonance imaging, which revealed a large sac of cerebrospinal fluid herniating through the anterior cranial fossa defect with strands of neurogenic tissue in direct contact with the tongue in the absence of the palate. Agenesis of the corpus callosum and the classic "Viking helmet" appearance of the frontal horns of the lateral ventricles were clearly visible.</AbstractText>Prenatal diagnosis of encephalocele is rarely reported. Unfortunately, the infant in this case report died at 3 months of age despite intensive medical therapy.</AbstractText>Copyright © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,868 | Isolated Intraventricular Chronic Mucormycosis in an Immunocompetent Infant: A Rare Case with Review of the Literature. | Mucormycosis of the central nervous system is an uncommon infection caused by saprophytic or parasitic fungi of the subphylum Mucormycotina and order Mucorales viz. Rhizopus, Mucor, and Rhizomucor. Isolated, chronic involvement of the central nervous system is a rare occurrence. To the best of our knowledge, isolated chronic ventricular involvement in an infant has not been reported previously. Isolated intracerebral mucormycosis is a disease of the immunocompromised patient, and to date only 6 cases have been reported in immunocompetent patients, including 2 pediatric cases.</AbstractText>We present the case of an immunocompetent infant presenting with features of increased intracranial tension. He underwent cerebrospinal fluid diversion and was found to harbor mucormycosis on histopathologic examination of intraventricular debris. We also present a brief review of the relevant literature.</AbstractText>Although mucormycosis is an acute fulminant infection, chronic isolated cerebral cases are known in the immunocompetent patient. Patients also may present with isolated hydrocephalus, and hence fungal infection must be ruled out in all, especially if a shunt is warranted.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,328,869 | Patterns of white matter hyperintensities associated with cognition in middle-aged cognitively healthy individuals. | White matter hyperintensities (WMH) are commonly detected in the brain of elderly individuals and have been associated with a negative impact on multiple cognitive domains. We aim to investigate the impact of global and regional distribution of WMH on episodic memory and executive function in middle-aged cognitively unimpaired participants [N = 561 (45-75 years)] enriched for Alzheimer's disease risk factors. WMH were automatically segmented from FLAIR, T1 and FSE MR images. WMH load was calculated both globally and regionally. At each cerebral lobe, regional WMH load was measured at four equidistant layers extending from the lateral ventricles to juxtacortical areas. Cognition was measured by The Memory Binding Test (MBT) and WAIS-IV subtests. Global composite z-scores were calculated for the two cognitive domains. Association between global and regional WMH measurements were sought against cognitive measures, both in global composite scores and in individual subtests. We adjusted cognition and WMH burden for the main sociodemographic (age, sex and education) and genetic factors (APOE-ε4). Memory and executive function were significantly associated with global WMH load. Regionally, lower executive performance was mainly associated with higher deep WMH load in frontal areas and, to a lower degree, in occipital, parietal and temporal regions. Lower episodic memory performance was correlated with higher WMH burden in deep frontal and occipital areas. Our novel methodological approach of regional analysis allowed us to reveal the association between cognition and WMH in strategic brain locations. Our results suggest that, even a small WMH load can impact cognition in cognitively unimpaired middle-aged subjects. |
2,328,870 | Surgical treatment for symptomatic ventriculus terminalis: case series and a literature review. | Ventriculus terminalis is a cystic embryological remnant within the conus medullaris that normally regresses after birth. In rare cases, it may persist into adulthood and give rise to neurological symptoms, for which the optimal treatment remains uncertain. The aim of this study was to present our experience from a population-based cohort of patients with ventriculus terminalis and discuss our management strategy as compared to the existing literature.</AbstractText>A retrospective review was conducted of all adult (≥ 15 years) patients with ventriculus terminalis who were referred to the Karolinska University Hospital between 2010 and 2018.</AbstractText>Fourteen patients were included. All patients were symptomatic at the time of referral, and the most common symptom was lower limb weakness (n = 9). Microsurgical cyst fenestration was offered to all patients and performed in thirteen. Postoperative imaging confirmed cyst size reduction in all surgically treated patients. No surgical complications were reported. Eleven of the surgically treated patients showed clinical improvement at long-term follow-up. One patient declined surgery, with progression of the cyst size and clinical deterioration observed at follow-up.</AbstractText>Surgery for ventriculus terminalis seems to be a safe and effective option for relief of symptoms. We propose that surgery should be offered to all patients with symptomatic ventriculus terminalis.</AbstractText> |
2,328,871 | An Electrical Model of Hydrocephalus Shunt Incorporating the CSF Dynamics. | The accumulation of cerebrospinal fluid (CSF) in brain ventricles and subarachnoid space is known as hydrocephalus. Hydrocephalus is a result of disturbances in the secretion or absorption process of CSF. A hydrocephalus shunt is an effective method for the treatment of hydrocephalus. In this paper, at first, the procedures of secretion, circulation, and absorption of CSF are studied and subsequently, the mathematical relations governing the pressures in different interacting compartments of the brain are considered. A mechanical-electrical model is suggested based on the brain physiology and blood circulation. In the proposed model, hydrocephalus is modeled with an incremental resistance (R<sub>o</sub>) and hydrocephalus shunt, which is a low resistance path to drain the accumulated CSF in the brain ventricles, is modeled with a resistance in series with a diode. At the end, the simulation results are shown. The simulation results can be used to predict the shunt efficiency in reducing CSF pressure and before a real shunt implementation surgery is carried out in a patient's body. |
2,328,872 | Respiratory influence on cerebrospinal fluid flow - a computational study based on long-term intracranial pressure measurements. | Current theories suggest that waste solutes are cleared from the brain via cerebrospinal fluid (CSF) flow, driven by pressure pulsations of possibly both cardiac and respiratory origin. In this study, we explored the importance of respiratory versus cardiac pressure gradients for CSF flow within one of the main conduits of the brain, the cerebral aqueduct. We obtained overnight intracranial pressure measurements from two different locations in 10 idiopathic normal pressure hydrocephalus (iNPH) patients. The resulting pressure gradients were analyzed with respect to cardiac and respiratory frequencies and amplitudes (182,000 cardiac and 48,000 respiratory cycles). Pressure gradients were used to compute CSF flow in simplified and patient-specific models of the aqueduct. The average ratio between cardiac over respiratory flow volume was 0.21 ± 0.09, even though the corresponding ratio between the pressure gradient amplitudes was 2.85 ± 1.06. The cardiac cycle was 0.25 ± 0.04 times the length of the respiratory cycle, allowing the respiratory pressure gradient to build considerable momentum despite its small magnitude. No significant differences in pressure gradient pulsations were found in the sleeping versus awake state. Pressure gradients underlying CSF flow in the cerebral aqueduct are dominated by cardiac pulsations, but induce CSF flow volumes dominated by respiration. |
2,328,873 | Short-term evaluation of cardiac morphology, function, metabolism and structure following diagnosis of adult-onset growth hormone deficiency. | The impact of growth hormone (GH) deficiency of the adult on cardiovascular function remains only partially elucidated. Purpose of this study was to test cardiac function in adult GH deficient patients using cardiac magnetic resonance (CMR).</AbstractText>Cardiac magnetic resonance (CMR) techniques, including cardiac 31</sup>P MR spectroscopy and evaluation of gadolinium late-enhancement, were applied to assess simultaneously, in a cross-sectional fashion, morphological, functional, metabolic, and structural parameters of the left (LV) and right ventricle (RV) in 15 patients with adult onset GH deficiency. Fifteen healthy individuals served as controls.</AbstractText>In GH deficient patients LV systolic function (EF%: 61 ± 1.7 vs 62.1 ± 0.8; p = .44) was not different in spite of a lower LV mass (83.2 ± 5.3 vs 145.3 ± 11.9 g; p = .001), a subclinical impairment of diastolic function (E/A peak ratio: 1.6 ± 0.2 vs 2.1 ± 0.2 p = .05), and a trend for lower PCr/ATP ratio (2.1 ± 0.8 vs 2.3 ± 0.1 p = .07). The RV showed reduced chamber size (end diastolic volume 123.8 ± 9 vs 147.9 ± 7.6 mL; p = .021) with preserved mass. No structural alterations of the LV and RV at late-enhancement were detected in these patients.</AbstractText>GH deficient patients represent a unique model of reduced LV myocardial mass in which major structural and metabolic alterations are lacking. Mal-adaptive mechanisms developing in the long term in response to GH deficiency and more severely affecting the LV remain to be elucidated.</AbstractText>Copyright © 2019 Elsevier Ltd. All rights reserved.</CopyrightInformation> |
2,328,874 | Establishment of patient-derived orthotopic xenograft model of 1q+ posterior fossa group A ependymoma. | Treatment for pediatric posterior fossa group A (PFA) ependymoma with gain of chromosome 1q (1q+) has not improved over the past decade owing partially to lack of clinically relevant models. We described the first 2 1q+ PFA cell lines, which have significantly enhanced our understanding of PFA tumor biology and provided a tool to identify specific 1q+ PFA therapies. However, cell lines do not accurately replicate the tumor microenvironment. Our present goal is to establish patient-derived xenograft (PDX) mouse models.</AbstractText>Disaggregated tumors from 2 1q+ PFA patients were injected into the flanks of NSG mice. Flank tumors were then transplanted into the fourth ventricle or lateral ventricle of NSG mice. Characterization of intracranial tumors was performed using imaging, histology, and bioinformatics.</AbstractText>MAF-811_XC and MAF-928_XC established intracranially within the fourth ventricle and retained histological, methylomic, and transcriptomic features of primary patient tumors. We tested the feasibility of treating PDX mice with fractionated radiation or chemotherapy. Mice tolerated radiation despite significant tumor burden, and follow-up imaging confirmed radiation can reduce tumor size. Treatment with fluorouracil reduced tumor size but did not appear to prolong survival.</AbstractText>MAF-811_XC and MAF-928_XC are novel, authentic, and reliable models for studying 1q+ PFA in vivo. Given the successful response to radiation, these models will be advantageous for testing clinically relevant combination therapies to develop future clinical trials for this high-risk subgroup of pediatric ependymoma.</AbstractText>© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</CopyrightInformation> |
2,328,875 | Red Cell Distribution Width and Platelet Count as Biomarkers of Pulmonary Arterial Hypertension in Patients with Connective Tissue Disorders. | <AbstractText Label="INTRODUCTION/OBJECTIVE" NlmCategory="OBJECTIVE">In the present paper, we aimed to test the value of the red cell distribution width (RDW) coefficient of variation as a candidate biomarker for pulmonary arterial hypertension (PAH) in patients with connective tissue disorders (CTD), correlating it with the degree of cardiopulmonary impairment in these patients.</AbstractText>The study population included N</i> = 141 patients with CTD and N</i> = 59 patients affected by pulmonary hypertension of other etiologies, all referred to the Pulmonary Hypertension Clinic of the Cardiology Division of an Academic Hospital in Northern Italy for evaluation (including right catheterization). Clinical, instrumental, and laboratory data were collected and related to RDW and other full blood count indexes.</AbstractText>Twenty out of 141 CTD patients (14%) received a diagnosis of PAH. In comparison to those without PAH, CTD patients with PAH displayed a larger RDW (14.9% (13.5-17.2) vs. 13.8% (13.1-15.0); p</i> = 0.02) and a lower platelet count (205 (177-240) × 109</sup>/l vs. 244 (197.5-304.2) × 109</sup>/l; p</i> = 0.005). Moreover, with respect to CTD patients without PAH, RDW was significantly larger also in PH of other etiologies. In contrast, the platelet count was significantly lower only in CTD-related PAH, with a value > 276 × 109</sup>/l being 100% sensitive in ruling out PAH. Finally, RDW, but not the platelet count, was related directly to systolic pulmonary arterial pressure (r</i> = 0.381; p</i> = 0.0008) and right ventricle diameter (r</i> = 0.283; p</i> = 0.015) and inversely to diffusing capacity of the lung for carbon monoxide (r</i> = -0.325; p</i> = 0.014).</AbstractText>RDW is a promising candidate biomarker for the screening and the prognostic stratification of PAH in CTD patients.</AbstractText> |
2,328,876 | Myocardial Blood Flow and Metabolic Rate of Oxygen Measurement in the Right and Left Ventricles at Rest and During Exercise Using <sup>15</sup>O-Labeled Compounds and PET. | <b>Aims:</b> Simultaneous measurement of right (RV) and left ventricle (LV) myocardial blood flow (MBF), oxygen extraction fraction (OEF), and oxygen consumption (MVO<sub>2</sub>) non-invasively in humans would provide new possibilities to understand cardiac physiology and different patho-physiological states. <b>Methods:</b> We developed and tested an optimized novel method to measure MBF, OEF, and MVO<sub>2</sub> simultaneously both in the RV and LV free wall (FW) using positron emission tomography in healthy young men at rest and during supine bicycle exercise. <b>Results:</b> Resting MBF was not significantly different between the three myocardial regions. Exercise increased MBF in the LVFW and septum, but MBF was lower in the RV compared to septum and LVFW during exercise. Resting OEF was similar between the three different myocardial regions (~70%) and increased in response to exercise similarly in all regions. MVO<sub>2</sub> increased approximately two to three times from rest to exercise in all myocardial regions, but was significantly lower in the RV during exercise as compared to septum LVFW. <b>Conclusion:</b> MBF, OEF, and MVO<sub>2</sub> can be assessed simultaneously in the RV and LV myocardia at rest and during exercise. Although there are no major differences in the MBF and OEF between LV and RV myocardial regions in the resting myocardium, MVO<sub>2</sub> per gram of myocardium appears to be lower the RV in the exercising healthy human heart due to lower mean blood flow. The presented method may provide valuable insights for the assessment of MBF, OEF and MVO<sub>2</sub> in hearts in different pathophysiological states. |
2,328,877 | The Bone Morphogenetic Protein Signaling Inhibitor LDN-193189 Enhances Metastasis Development in Mice. | Breast cancer with bone metastasis is essentially incurable with current anticancer therapies. The bone morphogenetic protein (BMP) pathway is an attractive therapeutic candidate, as it is involved in the bone turnover and in cancer cell formation and their colonization of distant organs such as the bone. We previously reported that in breast cancer cells, the ZNF217 oncogene drives BMP pathway activation, increases the metastatic growth rate in the bone, and accelerates the development of severe osteolytic lesions in mice. In the present study, we aimed at investigating the impact of the LDN-193189 compound, a potent inhibitor of the BMP type I receptor, on metastasis development <i>in vivo</i>. ZNF217-revLuc cells were injected into the left ventricle of nude mice (<i>n</i> = 16) while control mice (<i>n</i> = 13) were inoculated with control pcDNA6-revLuc cells. Mice from each group were treated or not with LDN-193189 for 35 days. We found that systemic LDN-193189 treatment of mice significantly enhanced metastasis development, by increasing both the number and the size of metastases. In pcDNA6-revLuc-injected mice, LDN-193189 also affected the kinetics of metastasis emergence. Altogether, these data suggest that <i>in vivo</i>, LDN-193189 might affect the interaction between breast cancer cells and the bone environment, favoring the emergence and development of multiple metastases. Hence, our report highlights the importance of the choice of drugs and therapeutic strategies used in the management of bone metastases. |
2,328,878 | New Neurons in the Post-ischemic and Injured Brain: Migrating or Resident? | The endogenous potential of adult neurogenesis is of particular interest for the development of new strategies for recovery after stroke and traumatic brain injury. These pathological conditions affect endogenous neurogenesis in two aspects. On the one hand, injury usually initiates the migration of neuronal precursors (NPCs) to the lesion area from the already existing, in physiological conditions, neurogenic niche - the ventricular-subventricular zone (V-SVZ) near the lateral ventricles. On the other hand, recent studies have convincingly demonstrated the local generation of new neurons near lesion areas in different brain locations. The striatum, cortex, and hippocampal CA1 region are considered to be locations of such new neurogenic zones in the damaged brain. This review focuses on the relative contribution of two types of NPCs of different origin, resident population in new neurogenic zones and cells migrating from the lateral ventricles, to post-stroke or post-traumatic enhancement of neurogenesis. The migratory pathways of NPCs have also been considered. In addition, the review highlights the advantages and limitations of different methodological approaches to the definition of NPC location and tracking of new neurons. In general, we suggest that despite the considerable number of studies, we still lack a comprehensive understanding of neurogenesis in the damaged brain. We believe that the advancement of methods for <i>in vivo</i> visualization and longitudinal observation of neurogenesis in the brain could fundamentally change the current situation in this field. |
2,328,879 | [Thyroid hormones regulate neural stem cell fate]. | Thyroid hormones (THs) are vital for vertebrate brain function throughout life, from early development to ageing. Epidemiological studies show an adequate supply of maternal TH during pregnancy to be necessary for normal brain development, and this from the first trimester of onwards. Maternal TH deficiency irreversibly affects fetal brain development, increasing the risk of offspring cognitive disorders and IQ loss. Mammalian and non-mammalian (zebrafish, xenopus, chicken) models are useful to dissect TH-dependent cellular and molecular mechanisms governing embryonic and fetal brain development: a complex process including cell proliferation, survival, determination, migration, differentiation and maturation of neural stem cells (NSCs). Notably, rodent models have strongly contributed to understand the key neurogenic roles of TH still at work in adult life. Neurogenesis continues in two main areas, the sub-ventricular zone lining the lateral ventricles (essential for olfaction) and the sub-granular zone in the dentate gyrus of the hippocampus (involved in memory, learning and mood control). In both niches, THs tightly regulate the balance between neurogenesis and oligodendrogenesis under physiological and pathological contexts. Understanding how THs modulate NSCs determination toward a neuronal or a glial fate throughout life is a crucial question in neural stem cell biology. Providing answers to this question can offer therapeutic strategies for brain repair, notably in neurodegenerative diseases, demyelinating diseases or stroke where new neurons and/or oligodendrocytes are required. The review focuses on TH regulation of NSC fate in mammals and humans both during development and in the adult. |
2,328,880 | Prevention of progression of pulmonary hypertension by the Nur77 agonist 6-mercaptopurine: role of BMP signalling. | Pulmonary arterial hypertension (PAH) is a progressive fatal disease characterised by abnormal remodelling of pulmonary vessels, leading to increased vascular resistance and right ventricle failure. This abnormal vascular remodelling is associated with endothelial cell dysfunction, increased proliferation of smooth muscle cells, inflammation and impaired bone morphogenetic protein (BMP) signalling. Orphan nuclear receptor Nur77 is a key regulator of proliferation and inflammation in vascular cells, but its role in impaired BMP signalling and vascular remodelling in PAH is unknown.We hypothesised that activation of Nur77 by 6-mercaptopurine (6-MP) would improve PAH by inhibiting endothelial cell dysfunction and vascular remodelling.Nur77 expression is decreased in cultured pulmonary microvascular endothelial cells (MVECs) and lungs of PAH patients. Nur77 significantly increased BMP signalling and strongly decreased proliferation and inflammation in MVECs. In addition, conditioned medium from PAH MVECs overexpressing Nur77 inhibited the growth of healthy smooth muscle cells. Pharmacological activation of Nur77 by 6-MP markedly restored MVEC function by normalising proliferation, inflammation and BMP signalling. Finally, 6-MP prevented and reversed abnormal vascular remodelling and right ventricle hypertrophy in the Sugen/hypoxia rat model of severe angioproliferative PAH.Our data demonstrate that Nur77 is a critical modulator in PAH by inhibiting vascular remodelling and increasing BMP signalling, and activation of Nur77 could be a promising option for the treatment of PAH. |
2,328,881 | Amiloride Alleviates Neurological Deficits Following Transient Global Ischemia and Engagement of Central IL-6 and TNF-α Signal. | Central pro-inflammatory cytokine (PIC) signal is involved in neurological deficits after transient global ischemia induced by cardiac arrest (CA). The present study was to examine if blocking acid sensing ion channels (ASICs) using amiloride in the Central Nervous System can alleviate neurological deficits after the induction of CA and further examine the participation of PIC signal in the hippocampus for the effects of amiloride.</AbstractText>CA was induced by asphyxia and then cardiopulmonary resuscitation was performed in rats. Western blot analysis and ELISA were used to determine the protein expression of ASIC subunit ASIC1 in the hippocampus, and the levels of PICs. As noted, it is unlikely that this procedure is clinically used although amiloride and other pharmacological agents were given into the brain in this study.</AbstractText>CA increased ASIC1 in the hippocampus of rats in comparison with control animals. This was associated with the increase in IL-1β, IL-6 and TNF-α together with Caspase-3 and Caspase-9. The administration of amiloride into the lateral ventricle attenuated the upregulation of Caspase-3/Caspase-9 and this further alleviated neurological severity score and brain edema. Inhibition of central IL-6 and TNF-α also decreased ASIC1 in the hippocampus of CA rats.</AbstractText>Transient global ischemia induced by CA amplifies ASIC1a in the hippocampus likely via PIC signal. Amiloride administered into the Central Nervous System plays a neuroprotective role in the process of global ischemia. Thus, targeting ASICs (i.e., ASIC1a) is suggested for the treatment and improvement of CA-evoked global cerebral ischemia.</AbstractText>Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.</CopyrightInformation> |
2,328,882 | Inhibition of Reactive Astrocytes with Fluorocitrate Ameliorates Learning and Memory Impairment Through Upregulating CRTC1 and Synaptophysin in Ischemic Stroke Rats. | Ischemic stroke often causes motor and cognitive deficits. Deregulated glia gap junction communication, which is reflected by increased protein levels of glial fibrillary acidic protein (GFAP) and connexin 43 (Cx43), has been observed in ischemic hippocampus and has been associated with cognitive impairment in animal stroke models. Here, we tested the hypothesis that reactive astrocytes-mediated loss of synaptophysin (SYP) and CREB-regulated transcription coactivator 1 (CRTC1) contribute to dysfunction in glia gap junction communication and memory impairment after ischemic stroke. Male Sprague-Dawley rats were subjected to a 90-min middle cerebral artery occlusion (MCAO) with 7-day reperfusion. Fluorocitrate (1 nmol), the reversible inhibitor of the astrocytic tricarboxylic acid cycle, was injected into the right lateral ventricle of MCAO rats once every 2 days starting immediately before reperfusion. The Morris water maze was used to assess memory in conjunction with western blotting and immunostaining to detect protein expression and distribution in the hippocampus. Our results showed that ischemic stroke caused significant memory impairment accompanied by increased protein levels of GFAP and Cx43 in hippocampal tissue. In addition, the levels of several key memory-related important proteins including SYP, CRTC1, myelin basic protein and high-mobility group-box-1 were significantly reduced in the hippocampal tissue. Of note, inhibition of reactive astrocytes with fluorocitrate was shown to significantly reverse the above noted changes induced by ischemic stroke. Taken together, our findings demonstrate that inhibiting reactive astrocytes with fluorocitrate immediately before reperfusion may protect against ischemic stroke-induced memory impairment through the upregulation of CRTC1 and SYP. |
2,328,883 | Beyond apical ballooning: computational modelling reveals morphological features of Takotsubo cardiomyopathy. | Takotsubo cardiomyopathy (TCM) is characterized by transient myocardial dysfunction, typically at the left ventricular (LV) apex. Its pathophysiology and recovery mechanisms remain unknown. We investigated LV morphology and deformation in n = 28 TCM patients. Patients with MRI within 5 days from admission ("early TCM") showed reduced LVEF and higher ventricular volumes, but no differences in ECG, global strains or myocardial oedema. Statistical shape modelling described LV size (Mode 1), apical sphericity (Mode 2) and height (Mode 3). Significant differences in Mode 1 suggest that "early TCM" LV remodeling is mainly influenced by a change in ventricular size rather than apical sphericity. |
2,328,884 | A fundamental evaluation of the electrical properties and function of cardiac transverse tubules. | This work discusses active and passive electrical properties of transverse (T-)tubules in ventricular cardiomyocytes to understand the physiological roles of T-tubules. T-tubules are invaginations of the lateral membrane that provide a large surface for calcium-handling proteins to facilitate sarcomere shortening. Higher heart rates correlate with higher T-tubular densities in mammalian ventricular cardiomyocytes. We assess ion dynamics in T-tubules and the effects of sodium current in T-tubules on the extracellular potential, which leads to a partial reduction of the sodium current in deep segments of a T-tubule. We moreover reflect on the impact of T-tubules on macroscopic conduction velocity, integrating fundamental principles of action potential propagation and conduction. We also theoretically assess how the conduction velocity is affected by different T-tubular sodium current densities. Lastly, we critically assess literature on ion channel expression to determine whether action potentials can be initiated in T-tubules. |
2,328,885 | EXPRESS: Left ventricular early diastolic strain rate detected by two-dimensional speckle tracking echocardiography and disease severity in pre-capillary pulmonary hypertension. | We investigated and compared the correlations between two-dimensional speckle tracking echocardiography detected left ventricular peak early diastolic strain rates (global: left ventricular global peak early diastolic strain rate; septum: left ventricular peak early diastolic strain rate of septum; free wall: left ventricular peak early diastolic strain rate of free wall) and disease severity in pre-capillary pulmonary hypertension. Seventy-four pre-capillary pulmonary hypertension patients (23 males and 51 females, 35 ± 13 years) and thirty healthy controls were consecutively recruited for two-dimensional speckle tracking echocardiography analyses in our study. Medical records of pre-capillary pulmonary hypertension patients were reviewed to capture clinical data; risk assessments were performed based on the 2015 ESC Guidelines. Compared with healthy controls, left ventricular global peak early diastolic strain rate was lower in pre-capillary pulmonary hypertension patients (1.11 ± 0.60 s<sup>−1</sup> versus 1.47 ± 0.45 s<sup>−1</sup>, P = 0.001), especially that of the septum (1.13 ± 0.58 s<sup>−1</sup> versus 1.68 ± 0.46 s<sup>−1</sup>, P<0.001). Linear correlation analyses showed significant but weak correlations between left ventricle diastolic parameters and peak oxygen consumption, N-terminal pro-brain natriuretic peptide, and conventional echocardiographic right ventricle parameters: E/E′, tricuspid annular plane systolic excursion, S′, and fractional area change. No or weak correlations were observed between left ventricle diastolic parameters and hemodynamics. Multivariate logistic regression analyses showed left ventricular global peak early diastolic strain rate (OR: 0.304; 95%CI: 0.101–0.911) and left ventricular peak early diastolic strain rate of septum (OR: 0.252; 95%CI: 0.075–0.848) independently predict intermediate–high risk of pulmonary hypertension patients, even adjusted by age, gender, and body mass index. Receive operating characteristic curves showed that all the three models had the capacity to predict intermediate–high risk of pulmonary hypertension patients, and the model including left ventricular peak early diastolic strain rate of septum showed the strongest predictive capacity (area under the curve = 0.76, 95%CI: 0.59–0.93). Two-dimensional speckle tracking echocardiography detected left ventricle diastolic function parameters are significantly correlated with clinical data and can independently predict intermediate–high risk in pre-capillary pulmonary hypertension patients; the dysfunction of interventricular septum may make major contribution. |
2,328,886 | The A30P α-synuclein mutation decreases subventricular zone proliferation. | Parkinson's disease (PD) is associated with olfactory defects in addition to dopaminergic degeneration. Dopaminergic signalling is necessary for subventricular zone (SVZ) proliferation and olfactory bulb (OB) neurogenesis. Alpha-synuclein (α-syn or Snca) modulates dopaminergic neurotransmission, and SNCA mutations cause familial PD, but how α-syn and its mutations affect adult neurogenesis is unclear. To address this, we studied a bacterial artificial chromosome transgenic mouse expressing the A30P SNCA familial PD point mutation on an Snca-/- background. We confirmed that the SNCA-A30P transgene recapitulates endogenous α-syn expression patterns and levels by immunohistochemical detection of endogenous α-syn in a wild-type mouse and transgenic SNCA-A30P α-syn protein in the forebrain. The number of SVZ stem cells (BrdU+GFAP+) was decreased in SNCA-A30P mice, whereas proliferating (phospho-histone 3+) cells were decreased in Snca-/- and even more so in SNCA-A30P mice. Similarly, SNCA-A30P mice had fewer Mash1+ transit-amplifying SVZ progenitor cells but Snca-/- mice did not. These data suggest the A30P mutation aggravates the effect of Snca loss in the SVZ. Interestingly, calbindin+ and calretinin (CalR)+ periglomerular neurons were decreased in both Snca-/-, and SNCA-A30P mice but tyrosine hydroxylase+ periglomerular OB neurons were only decreased in Snca-/- mice. Cell death decreased in the OB granule layer of Snca-/- and SNCA-A30P mice. In the same region, CalR+ numbers increased in Snca-/- and SNCA-A30P mice. Thus, α-syn loss and human A30P SNCA decrease SVZ proliferation, cell death in the OB and differentially alter interneuron numbers. Similar disruptions in human neurogenesis may contribute to the olfactory deficits, which are observed in PD. |
2,328,887 | Gaussian process emulation to accelerate parameter estimation in a mechanical model of the left ventricle: a critical step towards clinical end-user relevance. | In recent years, we have witnessed substantial advances in the mathematical modelling of the biomechanical processes underlying the dynamics of the cardiac soft-tissue. Gao et al. (Gao et al. 2017 J. R. Soc. Interface 14, 20170203 ( doi:10.1098/rsif.2017.0203 )) demonstrated that the parameters underlying the biomechanical model have diagnostic value for prognosticating the risk of myocardial infarction. However, the computational costs of parameter estimation are prohibitive when the goal lies in building real-time clinical decision support systems. This is due to the need to repeatedly solve the mathematical equations numerically using finite-element discretization during an iterative optimization routine. The present article presents a method for accelerating the inference of the constitutive parameters by using statistical emulation with Gaussian processes. We demonstrate how the computational costs can be reduced by about three orders of magnitude, with hardly any loss in accuracy, and we assess various alternative techniques in a comparative evaluation study based on simulated data obtained by solving the left ventricular model with the finite-element method, and real magnetic resonance images data for a human volunteer. |
2,328,888 | Canine Ependymoma: Diagnostic Criteria and Common Pitfalls. | Reports of canine ependymoma are generally restricted to single case reports with tumor incidence estimated at 2% to 3% of primary central nervous system (CNS) tumors. While most commonly reported in the lateral ventricle, tumors can occur anywhere in the ventricular system and in extraventricular locations. Rosettes and pseudorosettes are a common histologic feature; however, these features can be mimicked by other CNS neoplasms. Thirty-seven potential ependymoma cases were identified in a retrospective database search of 8 institutions, and a histologic review of all cases was conducted. Of 37 cases, 22 candidate cases were further subjected to a consensus histologic and immunohistochemical review, and only 5 of 37 (13.5%) were conclusively identified as ependymoma. The neuroanatomic locations were the lateral ventricle (3/5), third ventricle (1/5), and mesencephalic aqueduct (1/5). Subtypes were papillary (4/5) and tanycytic (1/5). Histologic features included rosettes (5/5), pseudorosettes (5/5), ependymal canals (2/5), tanycytic differentiation (1/5), blepharoplasts (1/5), ciliated cells (1/5), and high nuclear to cytoplasmic ratio (5/5). Immunolabeling for GFAP (4/4) and CKAE1/3 (3/4) was found in pseudorosettes, rosettes, and scattered individual neoplastic cells. Diffuse but variably intense cytoplasmic S100 immunolabeling was detected in 3 of 4 cases. Olig2 intranuclear immunolabeling was observed in less than 1% of the neoplastic cells (3/3). Tumors that had pseudorosettes and mimicked ependymoma included oligodendroglioma, choroid plexus tumor, pituitary corticotroph adenoma, papillary meningioma, and suprasellar germ cell tumor. These findings indicate that canine ependymoma is an extremely rare neoplasm with histomorphologic features that overlap with other primary CNS neoplasms. |
2,328,889 | The Prevalence of Cavum Septum Pellucidum in Mental Disorders Revealed by MRI: A Meta-Analysis. | The prevalence of cavum septum pellucidum (CSP) in mental disorders, particularly schizophrenia spectrum disorders and mood disorders, remains uncertain. The authors used a meta-analytical approach to determine the prevalence of CSP in mental disorders and to compare these with the prevalence of CSP in psychiatrically healthy comparison subjects.</AbstractText>PubMed and Embase were systematically searched for relevant articles published as of January 9, 2018. After a quality assessment of individual studies using the Newcastle-Ottawa Scale, a random-effects model within Stata statistical software was used to synthesize 25 eligible studies that included 2,392 patients with mental disorders and 1,445 psychiatrically healthy comparison subjects.</AbstractText>The prevalence of CSP of any size and large CSP was found to be significantly higher in individuals with mental disorders compared with healthy comparison subjects, and the prevalence of CSP in schizophrenia spectrum and mood disorders did not differ between the groups.</AbstractText>The meta-regression with predefined covariance indicated that imaging parameters were not associated with the heterogeneity among original studies; however, the mean age of enrolled subjects was identified as a possible source of heterogeneity. No publication bias was found.</AbstractText> |
2,328,890 | Benign Postnatal Outcome after Prenatal Diagnosis of Fetal Ventriculomegaly with Choroid Plexus Hyperplasia: A Case Report. | Prenatal counselling following the diagnosis of fetal ventriculomegaly is challenging. Fetal MRI (magnetic resonance imaging) can be helpful in characterizing ventriculomegaly severity and associated anomalies, hence contributing to prognosis establishment. Choroid plexus hyperplasia (CPH) is a rare entity characterized by enlargement of the choroid plexuses, usually progressing to severe hydrocephalus with an associated poor outcome. We present a case of CPH diagnosed by fetal MRI at 23 weeks of gestation following referral for ventriculomegaly. The pregnancy was carried to term and the child was monitored clinically and radiologically. Despite the persistence of enlarged choroid plexuses, the ventricular size has progressively decreased, and at the 4-year follow-up the child presented normal psychomotor development. This case highlights the added value of MRI in prenatal diagnosis of fetal ventriculomegaly and its management. The unusual benign outcome in this case can be considered for parental counselling when faced with a fetus with similar findings. |
2,328,891 | Quantitative and Visual Characteristics of Primary Central Nervous System Lymphoma on <sup>18</sup>F-FDG-PET. | Primary central nervous system lymphomas (PCNSLs) are rare progressive brain tumors, whose managements are significantly different from other solid tumors, especially glioblastomas. Therefore, an early diagnosis is of great significance. <sup>18</sup>F-fluorodeoxyglucose (FDG)-positron emission tomography (PET), which can measure the glucose metabolic rate in the brain, is an increasingly common tool for early diagnosis. Twenty-five immunocompetent patients with PCNSL were reviewed in this study to describe the general characteristics of PCNSL patients' <sup>18</sup>F-FDG-PET scans. Quantitative features included a radically enhanced maximum standardized uptake value (SUV<sub>max</sub>) with a mean value of 23.8 ± 7.9 and a 5.8 ± 1.8 mean ratio of tumor-to-normal contralateral cortex activity (T/N). Visual characteristics, such as favored locations in the brain, lesion numbers, tumor shape, metabolic inhibition, and structural shift were determined as well. PCNSL was found to favor the cortex, especially the frontal lobe, followed by the basal ganglia and corpus callosum. All PCNSLs were near the lateral ventricular area. Tumor shapes were subdivided into three groups: diffuse, round, and irregular patterns. Reduced radiation was observed in the ipsilateral cortex, the basal ganglia and the contralateral cerebellum. The lateral ventricles were prone to be compressed on the side ipsilateral to the tumor, pushing the midline towards the contralateral side of the brain. In conclusion, aside from SUV<sub>max</sub> and T/N values, other visual characteristics are also available to facilitate the differentiation of PCNSLs from other brain conditions on <sup>18</sup>F-FDG-PET scans. |
2,328,892 | Hyperbaric oxygen therapy for iatrogenic arterial gas embolism after CT-guided lung biopsy : A case report. | Iatrogenic arterial gas embolism (AGE) can be life-threatening. The only causal treatment is immediate hyperbaric oxygen therapy (HBOT). This article reports on a case of a 74-year-old male patient who underwent computed tomography (CT)-guided lung biopsy of suspect nodules after squamous cell carcinoma of the tonsils. During puncture, sudden cardiovascular arrest occurred. The CT scan documented severe arterial gas embolism in the aorta, spinal canal, left heart ventricle, and brain. The patient was then transferred to our hospital for HBOT. After the first HBOT, an additional CT scan showed regression of all gas inclusions. In the treatment of gas embolism, HBOT is considered the gold standard and is indispensable. It is primarily used to reduce acute bubble effects and to avoid secondary bubble effects. Unfortunately, the long persisting gas occlusions and perfusion deficits led to severe hypoxic brain damage and a poor prognosis for the patient. In this case report we present the management of (iatrogenic) arterial gas embolism and point out the necessity of immediate HBOT. Furthermore, we discuss the pathophysiology leading to arterial gas embolism on the basis of the gas laws. |
2,328,893 | Effects of PDE-5 Inhibition on the Cardiopulmonary System After 2 or 4 Weeks of Chronic Hypoxia. | In pulmonary hypertension (PH), hypoxia represents both an outcome and a cause of exacerbation. We addressed the question whether hypoxia adaptation might affect the mechanisms underlying PH alleviation through phosphodiesterase-5 (PDE5) inhibition.</AbstractText>Eight-week-old male Sprague-Dawley rats were divided into two groups depending on treatment (placebo or sildenafil, a drug inhibiting PDE5) and were exposed to hypoxia (10% O2</sub>) for 0 (t0, n = 9/10), 2 (t2, n = 5/5) or 4 (t4, n = 5/5) weeks. The rats were treated (0.3 mL i.p.) with either saline or sildenafil (1.4 mg/Kg per day).</AbstractText>Two-week hypoxia changed the body weight (- 31% vs. - 27%, respectively, P = NS), blood hemoglobin (+ 25% vs. + 27%, P = NS) and nitrates+nitrites (+ 175% vs. + 261%, P = 0.007), right ventricle fibrosis (+ 814% vs. + 317%, P < 0.0001), right ventricle hypertrophy (+ 84% vs. + 49%, P = 0.007) and systolic pressure (+ 108% vs. + 41%, P = 0.001), pulmonary vessel density (+ 61% vs. + 46%, P = NS), and the frequency of small (< 50 µm wall thickness) vessels (+ 35% vs. + 13%, P = 0.0001). Most of these changes were maintained for 4-week hypoxia, except blood hemoglobin and right ventricle hypertrophy that continued increasing (+ 52% vs. + 42%, P = NS; and + 104% vs. + 83%, P = 0.04). To further assess these observations, small vessel frequency was found to be linearly related with the right ventricle-developed pressure independent of hypoxia duration.</AbstractText>Thus, although hypoxia adaptation is not yet accomplished after 4 weeks, PH alleviation by PDE5 inhibition might nevertheless provide an efficient strategy for the management of this disease.</AbstractText> |
2,328,894 | Revealing Regional Associations of Cortical Folding Alterations with In Utero Ventricular Dilation Using Joint Spectral Embedding. | Fetal ventriculomegaly (VM) is a condition with dilation of one or both lateral ventricles, and is diagnosed as an atrial diameter larger than 10 mm. Evidence of altered cortical folding associated with VM has been shown in the literature. However, existing studies use a holistic approach (i.e., ventricle as a whole) based on diagnosis or ventricular volume, thus failing to reveal the spatially-heterogeneous association patterns between cortex and ventricle. To address this issue, we develop a novel method to identify spatially fine-scaled association maps between cortical development and VM by leveraging vertex-wise correlations between the growth patterns of both ventricular and cortical surfaces in terms of area expansion and curvature information. Our approach comprises multiple steps. In the first step, we define a joint graph Laplacian matrix using cortex-to-ventricle correlations. Next, we propose a spectral embedding of the cortex-to-ventricle graph into a common underlying space where their joint growth patterns are projected. More importantly, in the joint ventricle-cortex space, the vertices of associated regions from both cortical and ventricular surfaces would lie close to each other. In the final step, we perform clustering in the joint embedded space to identify associated sub-regions between cortex and ventricle. Using a dataset of 25 healthy fetuses and 23 fetuses with isolated non-severe VM within the age range of 26-29 gestational weeks, our results show that the proposed approach is able to reveal clinically relevant and meaningful regional associations. |
2,328,895 | Integrated Computational Analysis Highlights unique miRNA Signatures in the Subventricular Zone and Striatum of GM2 Gangliosidosis Animal Models. | This work explores for the first time the potential contribution of microRNAs (miRNAs) to the pathophysiology of the GM2 gangliosidosis, a group of Lysosomal Storage Diseases. In spite of the genetic origin of GM2 gangliosidosis, the cascade of events leading from the gene/protein defects to the cell dysfunction and death is not fully elucidated. At present, there is no cure for patients. Taking advantage of the animal models of two forms of GM2 gangliosidosis, Tay-Sachs (TSD) and Sandhoff (SD) diseases, we performed a microRNA screening in the brain subventricular zone (SVZ) and striatum (STR), which feature the neurogenesis and neurodegeneration states, respectively, in adult mutant mice. We found abnormal expression of a panel of miRNAs involved in lipid metabolism, CNS development and homeostasis, and neuropathological processes, highlighting region- and disease-specific profiles of miRNA expression. Moreover, by using a computational analysis approach, we identified a unique disease- (SD or TSD) and brain region-specific (SVZ vs. STR) miRNAs signatures of predicted networks potentially related to the pathogenesis of the diseases. These results may contribute to the understanding of GM2 gangliosidosis pathophysiology, with the aim of developing effective treatments. |
2,328,896 | Volume growth trend and correlation of atrial diameter with lateral ventricular volume in normal fetus and fetus with ventriculomegaly: A STROBE compliant article. | To explore the growth trend of fetal lateral ventricular volume, for understanding the relationship between atrial diameter (AD) and volume in normal fetus and fetus with ventriculomegaly.Overall, 97 sequential fetal head magnetic resonance imaging scans were performed; these pertained to 50 fetuses with normal lateral ventricles [normal group; gestational age (GA): 24-38 weeks] and 47 fetuses with ventriculomegaly (VM) (VM group; GA: 24-37 weeks). The left, right, and total lateral ventricular volume were measured using 3-dimensional magnetic resonance hydrography (MRH). Correlation coefficient (r) was calculated to assess the relationships of measurements. Lineal regression analysis was used to assess correlation of AD and GA with volume. Between-group differences in terms of AD and volume were assessed using t test.Significant linear growth was observed in the total lateral ventricular volume compared with GA in the normal group with a relative growth rate of 2.87% per week (P <.001). Significant linear relationship between AD and volume was observed, and a significant equation was acquired in the normal group and VM groups, respectively, using the simple linear regression model: left volume = 0.438 * normal left diameter (NLD) + 1.359; right volume = 0.493 * normal right diameter (NRD) + 1.012; left volume = 0.959 * left diameter in VM (VLD) - 2.074; right volume = 0.799 * right diameter in VM (VRD) - 0.443. A significant equation was obtained in the normal group and the VM group, using the multiple linear regression model: Total volume (mL) = 0.396 * NLD + 0.410 * NRD + 3.101; and total volume = 0.989 * VLD + 0.834 * VRD - 3.141, respectively. In terms of AD and volume, the left lateral ventricle was significantly larger than the right side in both groups. The volume of lateral ventricle in AD ≥10 mm group was larger than that in the AD <10 mm group. The total volume in the VM group was significantly larger than that in the normal group.The total lateral ventricular volume increased with GA. AD can be used to evaluate the fetal ventricular volume. |
2,328,897 | Spatial signature of dose patterns associated with acute radiation-induced lung damage in lung cancer patients treated with stereotactic body radiation therapy. | Thoracic radiation therapy (RT) is often associated with lung side effects, whose etiology is still controversial. Our aim was to explore correlations between local dose in the thoracic anatomy and the radiation-induced lung damage (RILD). To this end, we designed a robust scheme for voxel-based analysis (VBA) to explore dose patterns associated with RILD in non-small-cell lung cancer (NSCLC) patients receiving stereotactic body RT (SBRT). We analyzed 106 NSCLC SBRT patients (median prescription dose: 50 Gy; range: [40-54] Gy) in 4 fractions (range: [3-5]) with clinical and dosimetric records suitable for the analysis. The incidence of acute G1 RILD (RTOG grade  ⩾  1) was 68%. Each planning CT and dose map was spatially normalized to a common anatomical reference using a B-spline inter-patient registration algorithm after masking the gross tumor volume. The tumor-subtracted dose maps were converted into biologically effective dose maps (α/β  =  3 Gy). VBA was performed according to a non-parametric permutation test accounting for multiple comparison, based on a cluster analysis method. The underlying general linear model of RILD was designed to include dose maps and each non-dosimetric variable significantly correlated with RILD. The clusters of voxels with dose differences significantly correlated with RILD at a given p -level (S <sub>p </sub>) were generated. The only non-dosimetric variable significantly correlated with RILD was the chronic obstructive pulmonary disease (p   =  0.034). Patients with G1 RILD received significantly (p   ⩽  0.05) higher doses in two voxel clusters S <sub>0.05</sub> in the lower-left lung (14 cm<sup>3</sup>) and in an area (64 cm<sup>3</sup>) largely included within the ventricles. The applied VBA represents a powerful tool to probe the dose susceptibility of inhomogeneous organs in clinical radiobiology studies. The identified subregions with dose differences associated with G1 RILD in both the heart and lower lungs endorse a trend of previously reported hypotheses on lung toxicity radiobiology. |
2,328,898 | Hypothalamic nesfatin-1 mediates feeding behavior via MC3/4R-ERK signaling pathway after weight loss in obese Sprague-Dawley rats. | Nesfatin-1 is an anorexic peptide derived from nucleobindin 2 (NUCB2). An increase in hypothalamic nesfatin-1 inhibits feeding behavior and promotes weight loss. However, the effects of weight loss on hypothalamic nesfatin-1 levels are unclear. In this study, obese rats lost weight in three ways: Calorie Restriction diet (CRD), Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). We found an increase in nesfatin-1 serum and cerebrospinal fluid levels after weight loss in obese Sprague-Dawley (SD) rats. Moreover, weight loss also increased hypothalamic melanocortin 3/4 receptor (MC3/4R) and extracellular regulated kinase phosphorylation (p-ERK) signaling. Third ventricle administration of antisense morpholino oligonucleotide (MON) against the gene encoding NUCB2 inhibited hypothalamic nesfatin-1 and p-ERK signaling, increased food intake and reduced body weight loss in SG and RYGB obese rats. Third ventricle administration of SHU9119 (MC3/4R blocker) blocked hypothalamic MC3/4R, inhibited p-ERK signaling, increased food intake and reduced body weight loss in SG and RYGB obese rats. These findings indicate that weight loss leads to an increase in hypothalamic nesfatin-1. The increase in hypothalamic nesfatin-1 participates in regulating feeding behavior through the MC3/4R-ERK signaling especially after SG and RYGB. |
2,328,899 | Astrogliosis inhibition attenuates hydrocephalus by increasing cerebrospinal fluid reabsorption through the glymphatic system after germinal matrix hemorrhage. | Germinal matrix hemorrhage (GMH) results from the rupture of the immature thin-walled blood vessels and consequent bleeding into the subependymal germinal matrix and possible lateral ventricles. The purpose of this study is to investigate how astrogliosis impacts the glymphatic-meningeal lymphatic system in cerebrospinal fluid (CSF) reabsorption after GMH and how the anti-scarring agent olomoucine attenuates post-hemorrhagic hydrocephalus. GMH was induced by stereotaxic collagenase infusion into P7 Sprague-Dawley rats of both sexes. Western blot and immunofluorescence were used to assess astrogliosis and how astrogliosis affects glymphatic function by measuring Aquaporin-4 expression. Intracisternal injection of fluorescence tracer was used to measure CSF diffusion throughout the brain, its dispersion in the paravascular area and CSF drainage into the deep cervical lymph nodes at 28 days after GMH. Both short-term and long-term behavioral tests were used to assess the neurological outcomes. Nissl staining was used to assess the morphological changes at 28 days after hemorrhage. GMH elicited astrogliotic scarring and reduced the exchange between CSF and interstitial fluid, as well as CSF reabsorption through the meningeal lymphatic vessels. This might be associated with redistribution of Aquaporin-4. Olomoucine ameliorated scar tissue formation and attenuated post-hemorrhagic hydrocephalus. These findings of this study suggested that the glymphatic system might play a role in CSF reabsorption in neonates following GMH. Scar tissue formation impairs this CSF clearance route, and therefore astrogliosis inhibition might be a potential therapeutic strategy for neonatal post-hemorrhagic hydrocephalus. |
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