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2,331,000 | Characterization of germinal matrix hemorrhage in extremely premature infants: recognition of posterior location and diagnostic pitfalls. | Traditionally, descriptions of germinal matrix hemorrhage (GMH), derived from observations in preterm and very preterm infants, indicate its location at the caudothalamic grooves. However, before the germinal matrix begins to recede at approximately 28 weeks' gestational age (GA), it extends along the floor of the lateral ventricles far posterior to the caudothalamic grooves. Germinal matrix-intraventricular hemorrhage (GMH-IVH) can occur along any site from which the germinal matrix has not yet involuted. Therefore, as current advances in neonatology have allowed the routine survival of extremely preterm infants as young as 23 weeks' GA, postnatal GMH-IVH can occur in previously undescribed locations. Hemorrhage in the more posterior GMH on head ultrasound, if unrecognized, may lead to errors in diagnosis and mislocalization of this injury to the periventricular white matter or lateral walls of the lateral ventricles instead of to the subependyma, where it is in fact located.</AbstractText>Our aim is to describe posterior GMH in extremely premature infants, including its characteristic imaging appearance and potential pitfalls in diagnosis.</AbstractText>Over a 5-year period, all consecutive extremely preterm infants of 27 weeks' GA or less who developed GMH-IVH of any grade were included. A consecutive group of 100 very preterm infants of 31 weeks' GA with a GMH-IVH of any grade served as controls.</AbstractText>In 106 extremely preterm neonates (mean GA: 25 weeks, range: 23.1-26.6 weeks) with 212 potential lateral ventricular germinal matrix bleeding sites, 159 sites had bleeds. In 70/159 (44%), the GMH-IVH was located posterior to the caudothalamic grooves and the foramina of Monro, 52 (32.7%) were both anterior and posterior and 21 (13.2%) were exclusively anterior. In 16 ventricles with intraventricular hemorrhage, an origin site in the germinal matrix could not be determined. In the control population of very preterm infants, all hemorrhages were at the anterior caudothalamic grooves and 95% were grade I.</AbstractText>Unlike the older very preterm and moderately preterm infants that form the basis of our GMH-IVH description and classification, the extremely preterm infants now routinely surviving have a more fetal pattern of germinal matrix distribution, which is reflected in a different distribution and size of germinal matrix injury. We report the postnatal occurrence of subependymal GMH-IVH in extremely preterm infants in these more primitive, posterior locations, its potential imaging pitfalls and sonographic findings.</AbstractText>© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</CopyrightInformation> |
2,331,001 | Ventriculoperitoneal Shunt Drainage Increases With Gravity and Cerebrospinal Fluid Pressure Pulsations: Benchtop Model. | There have been few improvements in cerebrospinal fluid (CSF) shunt technology since John Holter introduced the silicon valve, with overdrainage remaining a major source of complications.</AbstractText>To better understand why valves are afflicted by supra-normal CSF flow rates. We present in Vitro benchtop analyses of flow through a differential pressure valve under simulated physiological conditions.</AbstractText>The pseudo-ventricle benchtop valve testing platform that comprises a rigid pseudo-ventricle, compliance chamber, pulsation generator, and pressure sensors was used to measure flow rates through a differential pressure shunt valve under the following simulated physiological conditions: orientation (horizontal/vertical), compliance (low/medium/high), and pulsation generator force (low/medium/high).</AbstractText>Our data show that pulse pressures are faithfully transmitted from the ventricle to the valve, that lower compliance and higher pulse generator forces lead to higher pulse pressures in the pseudo-ventricle, and that both gravity and higher pulse pressure lead to higher flow rates. The presence of a valve mitigates but does not eliminate these higher flow rates.</AbstractText>Shunt valves are prone to gravity-dependent overdrainage, which has motivated the development of gravitational valves and antisiphon devices. This study shows that overdrainage is not limited to the vertical position but that pulse pressures that simulate rhythmic (eg, cardiac) and provoked (eg, Valsalva) physiological CSF pulsations increase outflow in both the horizontal and vertical positions and are dependent on compliance. A deeper understanding of the physiological parameters that affect intracranial pressure and flow through shunt systems is prerequisite to the development of novel valves.</AbstractText>© Congress of Neurological Surgeons 2021.</CopyrightInformation> |
2,331,002 | A <i>de novo</i> Variant of <i>ASXL1</i> Is Associated With an Atypical Phenotype of Bohring-Opitz Syndrome: Case Report and Literature Review. | Bohring-Opitz syndrome (BOS) is a rare genetic disease first reported by Bohring et al. in 1999. With the recent development of exome sequencing (ES), <i>de novo</i> truncating mutations in the additional sex-combs-like 1 (<i>ASXL1</i>) gene have been causally implicated in BOS. Herein, we describe a 7-month-old girl with intrauterine growth restriction, severe pulmonary infection, seizures, and craniofacial abnormalities (microcephaly, micro/retrognathia, hypertelorism, depressed nasal bridge, low-set ears and hypertrichosis) at birth. At a later stage, the patient developed global developmental delay. We performed ES and identified a <i>de novo</i> heterozygous mutation in <i>ASXL1</i>, namely, c.1210C>T/p.R404<sup>*</sup>. However, this case did not have trigonocephaly, facial hemangioma, prominent eyes, myopia, BOS posture, or brain abnormalities (enlarged subarachnoid spaces, agenesis of the corpus callosum, moderately enlarged cerebral ventricles, or prominent frontal subarachnoid spaces), which are common characteristics in most patients with BOS-harboring <i>ASXL1</i> mutations. These new data expand the phenotype of BOS driven by <i>ASXL1</i> and may assist in more accurately delineating the phenotypes caused by variants of this gene. |
2,331,003 | Ruptured intraventricular tuberculous brain abscess mimicking cystic neoplasm: a case report. | Central nervous system (CNS) tuberculosis is a potentially life-threatening condition that may manifest in different forms and simulate other pathologies. It rarely involves the ventricles and the occurrence of primary intraventricular tuberculous brain abscess (TBA) has exceptionally been reported. As far as we know, ruptured intraventricular TBA has not been described before. An immunocompetent 56-years-old man was admitted for sub-acute intracranial hypertension with behaviour disorders. Cranial magnetic resonance imaging (MRI) showed a cystic lesion of the third ventricle containing fluid-fluid level with biventricular hydrocephalus and debris in the occipital horns. A ruptured cystic neoplasm was first considered. The patient underwent surgery via a right transcortical transventricular approach, combining both microscope and endoscope. The puncture of the lesion brought pus and the Ziehl-Neelson (ZN) staining demonstrated acid-fast bacilli. Intraventricular tuberculous abscess is an extremely rare condition that can take an unusual radiological appearance. This observation highlights the consideration of tuberculosis within the list of differential diagnosis of intraventricular cystic lesions in immunocompetent hosts. |
2,331,004 | Respiratory-driven Cyclic Cerebrospinal Fluid Motion in the Intracranial Cavity on Magnetic Resonance Imaging: Insights into the Pathophysiology of Neurofluid Dysfunction. | Neurofluids, a recently developed term that refers to interstitial fluids in the parenchyma and cerebrospinal fluid (CSF) in the ventricle and subarachnoid space, play a role in draining waste products from the brain. Neurofluids have been implicated in pathological conditions such as Alzheimer's disease and normal pressure hydrocephalus. Given that CSF moves faster in the CSF cavity than in the brain parenchyma, CSF motion can be detected by magnetic resonance imaging. CSF motion is synchronized to the heartbeat and respiratory cycle, but respiratory cycle-induced CSF motion has yet to be investigated in detail. Therefore, we analyzed CSF motion using dynamic improved motion-sensitized driven-equilibrium steady-state free precession-based analysis. We analyzed CSF motion linked to the respiratory cycle in four women and six men volunteers aged 23 to 38 years. We identified differences between free respiration and tasked respiratory cycle-associated CSF motion in the ventricles and subarachnoid space. Our results indicate that semi-quantitative analysis can be performed using the cranial site at which CSF motion is most prominent as a standard. Our findings may serve as a reference for elucidating the pathophysiology of diseases caused by abnormalities in neurofluids. |
2,331,005 | The Glymphatic System: A Novel Component of Fundamental Neurobiology. | Throughout the body, lymphatic fluid movement supports critical functions including clearance of excess fluid and metabolic waste. The glymphatic system is the analog of the lymphatic system in the CNS. As such, the glymphatic system plays a key role in regulating directional interstitial fluid movement, waste clearance, and, potentially, brain immunity. The glymphatic system enables bulk movement of CSF from the subarachnoid space along periarterial spaces, where it mixes with interstitial fluid within the parenchyma before ultimately exiting from the parenchyma via perivenous spaces. This review focuses on important questions about the structure of this system, why the brain needs a fluid transport system, and unexplored aspects of brain fluid transport. We provide evidence that astrocytes and blood vessels determine the shape of the perivascular space, ultimately controlling the movement of perivascular fluid. Glymphatic fluid movement has the potential to alter local as well as global transport of signaling molecules and metabolites. We also highlight the evidence for cross talk among the glymphatic system, cardiovascular system, gastrointestinal tract, and lymphatic system. Much remains to be studied, but we propose that the glymphatic/lymphatic system acts as a cornerstone in signaling between the brain and body. |
2,331,006 | Direct measurement of pulse wave propagation in capillaries of the human retina. | With each contraction of the heart's left ventricle, a pulse pressure wave surges into the aorta and propagates throughout the vascular tree. The pulse wave drives blood flow forward. Its passage is complex, but it passes more quickly through non-compliant, or stiff, vessels, providing an important signpost of cardiovascular disease. The transparent media of the eye allow direct and non-invasive measurement of this phenomenon within the microvasculature of neural tissue. However, previous estimates differ over three orders of magnitude. Here, we used high spatiotemporal resolution adaptive optics imaging to directly track the pulse wave within individual retinal capillaries in three human subjects. Across 74 unique capillary segments, pulse wave velocity averaged 6.4±0.5<i>m</i><i>m</i>/<i>s</i><i>e</i><i>c</i> (<i>m</i><i>e</i><i>a</i><i>n</i>±<i>S</i><i>E</i><i>M</i>). There was large variation between vessels; the slowest pulse wave was at most 0.8 mm/sec and the fastest at least 17.6 mm/sec. In 44% of vessels, the pulse wave traveled upstream, in the opposite direction to flow, suggesting wave reflection from downstream collecting junctions. |
2,331,007 | Inhalation of 2% Hydrogen Improves Survival Rate and Attenuates Shedding of Vascular Endothelial Glycocalyx in Rats with Heat Stroke. | Heat stroke is characterized by excessive oxidative stress and inflammatory responses, both of which are implicated in vascular endothelial glycocalyx shedding and heat-stroke mortality. Although molecular hydrogen has antioxidation and anti-inflammatory potency, its effect on the vascular endothelial glycocalyx in heat stroke has not been examined. Therefore, the aim of this study was to investigate the influence of hydrogen inhalation on the survival and thickness of the vascular endothelial glycocalyx of rats subjected to heat stroke. Altogether, 98 Wistar rats were assigned to the experiments. A heat-controlled chamber set at 40°C temperature and 60% humidity was used to induce heat stroke. After preparation, the anesthetized rats that underwent the heating process were subjected to an hour of stabilization in which 0%, 2%, or 4% hydrogen gas was inhaled and maintained until the experiment ended. In addition to survival rate assessments, blood samples and left ventricles were collected to evaluate the thickness of the vascular endothelial glycocalyx and relevant biomarkers. The results showed that 2% hydrogen gas significantly improved survival in the heat-stroked rats and partially preserved the thickness of the endothelial glycocalyx. In addition, serum levels of endotoxin, syndecan-1, malondialdehyde, and tumor necrosis factor-α decreased, whereas superoxide dismutase levels increased, indicating that inhalation of 2% hydrogen attenuated the damage to the vascular endothelial glycocalyx through its antioxidative and anti-inflammatory effects. |
2,331,008 | The association of left ventricular histologically verified myocardial fibrosis with pulmonary hypertension in severe aortic stenosis.<Pagination><StartPage>165</StartPage><EndPage>171</EndPage><MedlinePgn>165-171</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1177/02676591211042733</ELocationID><Abstract><AbstractText Label="OBJECTIVES">To evaluate the association between histologically verified left ventricular (LV) myocardial fibrosis (MF) and its bio- and functional markers with pulmonary hypertension (PH) in severe aortic stenosis (AS).</AbstractText><AbstractText Label="METHODS">About 34 patients with isolated severe AS underwent 2D echocardiography, cardiac magnetic resonance (CMR) imaging, and plasma NT-proBNP evaluation before aortic valve replacement (AVR). LV measurements were analyzed by CMR and LV strain using feature tracking software (Medis Suite QStrain 2.0). Myocardial biopsy sampled at the time of AVR was assessed by a histomorphometric analysis. PH was defined as pulmonary artery systolic pressure (PASP) ⩾ 45 mm Hg.</AbstractText><AbstractText Label="RESULTS">Patients with severe AS and PH (mean PASP 53 ± 3.7 mm Hg) had higher extent of diffuse MF versus patients without PH (12 (10.4-12.7)% vs 6.6 (4.6-8.2)% (p = 0.00)). The extent of diffuse MF correlated with LV dilatation (<i>r</i> = 0.7, p = 0.02), indices of LV dysfunction (lower ejection fraction (<i>r</i> = -0.6, p < 0.001), global longitudinal (<i>r</i> = -0.5, p = 0.02) and circumferential strain (<i>r</i> = -0.5, p = 0.05), elevated NT-proBNP (<i>r</i> = 0.5, p = 0.005) and elevated PASP (<i>r</i> = 0.6, p < 0.001)). Histological MF > 10% (AUC 94.9%), LV global longitudinal strain > -15.5% (AUC 86.3%), and NT-proBNP > 2090 ng/l (AUC 85.1%) were independent predictors of PH in severe AS.</AbstractText><AbstractText Label="CONCLUSIONS">The extent of diffuse myocardial fibrosis in combination with reduced longitudinal left ventricular strain and increased plasma levels of NT-proBNP relates to pulmonary hypertension in severe aortic stenosis.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Gumauskiene</LastName><ForeName>Birute</ForeName><Initials>B</Initials><Identifier Source="ORCID">0000-0003-2655-2105</Identifier><AffiliationInfo><Affiliation>Department of Cardiology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Drebickaite</LastName><ForeName>Egle</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Department of Cardiology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pangonyte</LastName><ForeName>Dalia</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Institute of Cardiology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vaskelyte</LastName><ForeName>Jolanta Justina</ForeName><Initials>JJ</Initials><AffiliationInfo><Affiliation>Department of Cardiology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Cardiology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Padervinskiene</LastName><ForeName>Lina</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Radiology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jakuska</LastName><ForeName>Povilas</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Cardiac, Thoracic and Vascular Surgery, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Budrikis</LastName><ForeName>Algimantas</ForeName><Initials>A</Initials><Identifier Source="ORCID">0000-0002-4022-2658</Identifier><AffiliationInfo><Affiliation>Department of Cardiac, Thoracic and Vascular Surgery, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ereminas</LastName><ForeName>Rokas</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Cardiac, Thoracic and Vascular Surgery, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ereminiene</LastName><ForeName>Egle</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Department of Cardiology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>09</Month><Day>15</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Perfusion</MedlineTA><NlmUniqueID>8700166</NlmUniqueID><ISSNLinking>0267-6591</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006976" MajorTopicYN="Y">Hypertension, Pulmonary</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001021" MajorTopicYN="N">Aortic Valve</DescriptorName><QualifierName UI="Q000601" MajorTopicYN="N">surgery</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001024" MajorTopicYN="Y">Aortic Valve Stenosis</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006352" MajorTopicYN="N">Heart Ventricles</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005355" MajorTopicYN="N">Fibrosis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016277" MajorTopicYN="N">Ventricular Function, Left</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013318" MajorTopicYN="N">Stroke Volume</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">aortic stenosis</Keyword><Keyword 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J Am Coll Cardiol 2017; 69: 1755–1756.</Citation><ArticleIdList><ArticleId IdType="pubmed">28359524</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">34524040</PMID><DateRevised><Year>2022</Year><Month>04</Month><Day>26</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1360-046X</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2021</Year><Month>Sep</Month><Day>15</Day></PubDate></JournalIssue><Title>British journal of neurosurgery</Title><ISOAbbreviation>Br J Neurosurg</ISOAbbreviation></Journal>"Extra-cranial proximal pica aneurysm - a rare and surreptious cause of posterior fossa sah: case report and review of literature". | To evaluate the association between histologically verified left ventricular (LV) myocardial fibrosis (MF) and its bio- and functional markers with pulmonary hypertension (PH) in severe aortic stenosis (AS).</AbstractText>About 34 patients with isolated severe AS underwent 2D echocardiography, cardiac magnetic resonance (CMR) imaging, and plasma NT-proBNP evaluation before aortic valve replacement (AVR). LV measurements were analyzed by CMR and LV strain using feature tracking software (Medis Suite QStrain 2.0). Myocardial biopsy sampled at the time of AVR was assessed by a histomorphometric analysis. PH was defined as pulmonary artery systolic pressure (PASP) ⩾ 45 mm Hg.</AbstractText>Patients with severe AS and PH (mean PASP 53 ± 3.7 mm Hg) had higher extent of diffuse MF versus patients without PH (12 (10.4-12.7)% vs 6.6 (4.6-8.2)% (p = 0.00)). The extent of diffuse MF correlated with LV dilatation (r</i> = 0.7, p = 0.02), indices of LV dysfunction (lower ejection fraction (r</i> = -0.6, p < 0.001), global longitudinal (r</i> = -0.5, p = 0.02) and circumferential strain (r</i> = -0.5, p = 0.05), elevated NT-proBNP (r</i> = 0.5, p = 0.005) and elevated PASP (r</i> = 0.6, p < 0.001)). Histological MF > 10% (AUC 94.9%), LV global longitudinal strain > -15.5% (AUC 86.3%), and NT-proBNP > 2090 ng/l (AUC 85.1%) were independent predictors of PH in severe AS.</AbstractText>The extent of diffuse myocardial fibrosis in combination with reduced longitudinal left ventricular strain and increased plasma levels of NT-proBNP relates to pulmonary hypertension in severe aortic stenosis.</AbstractText> |
2,331,009 | Correlation of fetal ventricular size and need for postnatal cerebrospinal fluid diversion surgery in open spina bifida. | Open spina bifida is a common cause of hydrocephalus in the postnatal period. In-utero closure of the fetal spinal defect decreases the need for postnatal cerebrospinal fluid (CSF) diversion surgery. Good prenatal predictors of the need for postnatal CSF diversion surgery are currently lacking. In this study, we aimed to assess the association of fetal ventriculomegaly and its progression over the course of pregnancy with the rate of postnatal hydrocephalus requiring intervention.</AbstractText>In this retrospective study, fetuses with a prenatal diagnosis of open spina bifida were assessed longitudinally. Ventricular diameter, as well as other potential predictors of the need for postnatal CSF diversion surgery, were compared between fetuses undergoing prenatal closure and those undergoing postnatal repair.</AbstractText>The diameter of the lateral ventricle increased significantly throughout gestation in both groups, but there was no difference in maximum ventricular diameter at first or last assessment between fetuses undergoing prenatal closure and those undergoing postnatal repair. There was no significant difference in the rate of progression of ventriculomegaly between the two groups, with a mean progression rate of 0.83 ± 0.5 mm/week in the prenatal-repair group and 0.6 ± 0.6 mm/week in the postnatal-repair group (P = 0.098). Fetal repair of open spina bifida was associated with a lower rate of postnatal CSF diversion surgery (P < 0.001). In all subjects, regardless of whether they had prenatal or postnatal surgery, the severity of ventriculomegaly at first and last assessments was associated independently with the need for postnatal CSF diversion surgery (P = 0.005 and P = 0.001, respectively), with a greater need for surgery in fetuses with larger ventricular size, even after controlling for gestational age at assessment.</AbstractText>In fetuses with open spina bifida, fetal ventricular size increases regardless of whether spina bifida closure is performed prenatally or postnatally, but the need for CSF diversion surgery is significantly lower in those undergoing prenatal repair. Ventriculomegaly is associated independently with the need for postnatal CSF diversion in fetuses with open spina bifida, irrespective of timing of closure. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.</AbstractText>© 2021 International Society of Ultrasound in Obstetrics and Gynecology.</CopyrightInformation> |
2,331,010 | Cesarean section in patient with metastatic Ewing sarcoma requiring VA-ECMO support. | A 26-year-old pregnant woman, with multiple metastatic Ewing sarcoma, presented with a sternal mass that began enlarging during pregnancy. Due to high-risk pregnancy, the patient was discussed in a multidisciplinary meeting and intubation was considered too risky without cardiopulmonary support. Computed tomography showed extrinsic tumor compression of the right ventricle outflow tract. Veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) was initiated before general anesthesia, followed by Cesarean section (C-section). VA ECMO was initiated with the patient in the awake position, ECMO support was discontinued when the patient had stable ventilation and hemodynamics. This case represents a unique indication of VA ECMO, during C-section, with maternal and fetal survival. |
2,331,011 | Sleep disturbances in craniopharyngioma: a challenging diagnosis. | Craniopharyngiomas are rare solid or mixed solid and cystic tumors that arise from Rathke's pouch remnants along the pituitary-hypothalamic axis, from the sella turcica to the brain third ventricle. Both the tumor and its treatment can lead to significant neurological and endocrinological complications. Due to the essential role of the hypothalamus in the complex neurophysiologic process of sleep, tumors involving the hypothalamic area may be responsible for disturbances in sleep-wake regulation with alterations in the circadian rhythm, sleep fragmentation, and increased daytime sleepiness. We report two cases of patients with craniopharyngioma, who came to our attention due to the occurrence of episodes characterized by psychomotor slowing and afinalistic limb movements, temporal and spatial disorientation, psychomotor agitation, and oneiric stupor like episodes. A comprehensive clinical data collection and a targeted diagnostic work-up led to a diagnosis of severe sleep disorder characterized by hypersomnia, altered sleep-wake rhythm, and sleep-related breathing disorder. In addition, the polysomnography revealed peculiar alterations in the sleep structure. The diagnostic work-up lead to an accurate differential diagnosis between epileptic seizures and episodes expressions of sleep disturbances. These clinical features can be challenging to diagnose and can lead to misdiagnosis and inappropriate treatment. Diagnosis of sleep disorders is crucial, considering the impact of sleep on general health, cognition, and neuropsychological functioning. These findings support the need to incorporate a comprehensive sleep evaluation in childhood brain tumor involving the suprasellar/hypothalamic region. |
2,331,012 | Huge Hydatid Cyst of the Right Ventricular Outflow Tract. | Hydatid disease is a common health problem in sheep-farming countries such as Iran. The liver and lungs are the most common primary sites of hydatid cysts in humans. Cardiac involvement is an uncommon manifestation, and the right ventricle outflow tract (RVOT) is rarely involved. This is a case report of a 34-year-old man who presented to the Heart Clinic, Tehran, Iran, in 2019 with a history of dyspnoea and fatigue. Following an imaging study, the patient was diagnosed with an RVOT hydatid cyst. He underwent surgical resection of the cyst. The post-operative course was uneventful. |
2,331,013 | Intracerebroventricular injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer's disease dementia: a phase I clinical trial. | Alzheimer's disease is the most common cause of dementia, and currently, there is no disease-modifying treatment. Favorable functional outcomes and reduction of amyloid levels were observed following transplantation of mesenchymal stem cells (MSCs) in animal studies.</AbstractText>We conducted a phase I clinical trial in nine patients with mild-to-moderate Alzheimer's disease dementia to evaluate the safety and dose-limiting toxicity of three repeated intracerebroventricular injections of human umbilical cord blood-derived MSCs (hUCB-MSCs).</AbstractText>We recruited nine mild-to-moderate Alzheimer's disease dementia patients from Samsung Medical Center, Seoul, Republic of Korea. Four weeks prior to MSC administration, the Ommaya reservoir was implanted into the right lateral ventricle of the patients. Three patients received a low dose (1.0 × 107</sup> cells/2 mL), and six patients received a high dose (3.0 × 107</sup> cells/2 mL) of hUCB-MSCs. Three repeated injections of MSCs were performed (4-week intervals) in all nine patients. These patients were followed up to 12 weeks after the first hUCB-MSC injection and an additional 36 months in the extended observation study.</AbstractText>After hUCB-MSC injection, the most common adverse event was fever (n = 9) followed by headache (n = 7), nausea (n = 5), and vomiting (n = 4), which all subsided within 36 h. There were three serious adverse events in two participants that were considered to have arisen from the investigational product. Fever in a low dose participant and nausea with vomiting in another low dose participant each required extended hospitalization by a day. There were no dose-limiting toxicities. Five participants completed the 36-month extended observation study, and no further serious adverse events were observed.</AbstractText>Three repeated administrations of hUCB-MSCs into the lateral ventricle via an Ommaya reservoir were feasible, relatively and sufficiently safe, and well-tolerated. Currently, we are undergoing an extended follow-up study for those who participated in a phase IIa trial where upon completion, we hope to gain a deeper understanding of the clinical efficacy of MSC AD therapy.</AbstractText>ClinicalTrials.gov NCT02054208. Registered on 4 February 2014. ClinicalTrials.gov NCT03172117. Registered on 1 June 2017.</AbstractText>© 2021. The Author(s).</CopyrightInformation> |
2,331,014 | Dopamine regulates adult neurogenesis in the ventricular-subventricular zone via dopamine D3 angiotensin type 2 receptor interactions. | Adult neurogenesis is a dynamic and highly regulated process, and different studies suggest that dopamine modulates ventricular-subventricular zone (V-SVZ) neurogenesis. However, the specific role of dopamine and the mechanisms/factors underlying its effects on physiological and pathological conditions such as Parkinson's disease (PD) are not fully understood. Recent studies have described counter-regulatory interactions between renin-angiotensin system (RAS) and dopamine in peripheral tissues and in the nigrostriatal system. We have previously demonstrated that angiotensin receptors regulate proliferation and generation of neuroblasts in the rodent V-SVZ. However, possible interactions between dopamine receptors and RAS in the V-SVZ and their role in alterations of neurogenesis in animal models of PD have not been investigated. In V-SVZ cultures, activation of dopamine receptors induced changes in the expression of angiotensin receptors. Moreover, dopamine, via D2-like receptors and particularly D3 receptors, increased generation of neurospheres derived from the V-SVZ and this effect was mediated by angiotensin type-2 (AT2) receptors. In rats, we observed a marked reduction in proliferation and generation of neuroblasts in the V-SVZ of dopamine-depleted animals, and inhibition of AT1 receptors or activation of AT2 receptors restored proliferation and generation of neuroblasts to control levels. Moreover, intrastriatal mesencephalic grafts partially restored proliferation and generation of neuroblasts observed in the V-SVZ of dopamine-depleted rats. Our data revealed that dopamine and angiotensin receptor interactions play a major role in the regulation of V-SVZ and suggest potential beneficial effects of RAS modulators on the regulation of adult V-SVZ neurogenesis. |
2,331,015 | Effect of modulating glutamate signaling on myelinating oligodendrocytes and their development-A study in the zebrafish model. | Myelination is crucial for the development and maintenance of axonal integrity, especially fast axonal action potential conduction. There is increasing evidence that glutamate signaling and release through neuronal activity modulates the myelination process. In this study, we examine the effect of manipulating glutamate signaling on myelination of oligodendrocyte (OL) lineage cells and their development in zebrafish (zf). We use the "intensity-based glutamate-sensing fluorescent reporter" (iGluSnFR) in the zf model (both sexes) to address the hypothesis that glutamate is implicated in regulation of myelinating OLs. Our results show that glial iGluSnFR expression significantly reduces OL lineage cell number and the expression of myelin markers in larvae (zfl) and adult brains. The specific glutamate receptor agonist, L-AP4, rescues this iGluSnFR effect by significantly increasing the expression of the myelin-related genes, plp1b and mbpa, and enhances myelination in L-AP4-injected zfl compared to controls. Furthermore, we demonstrate that degrading glutamate using Glutamat-Pyruvate Transaminase (GPT) or the blockade of glutamate reuptake by L-trans-pyrrolidine-2,4-dicarboxylate (PDC) significantly decreases myelin-related genes and drastically declines myelination in brain ventricle-injected zfl. Moreover, we found that myelin-specific ClaudinK (CldnK) and 36K protein expression is significantly decreased in iGluSnFR-expressing zfl and adult brains compared to controls. Taken together, this study confirms that glutamate signaling is directly required for the preservation of myelinating OLs and for the myelination process itself. These findings further suggest that glutamate signaling may provide novel targets to therapeutically boost remyelination in several demyelinating diseases of the CNS. |
2,331,016 | Neonatal hydrocephalus: an atypical presentation of malignant infantile osteopetrosis. | Autosomal recessive osteopetrosis has a variable presentation, most commonly including failure to thrive, hypocalcemia, seizures, hepatosplenomegaly, hydrocephalus, vision or hearing loss, and cytopenias. Multiple symptoms are usually seen at presentation. The variability of presentation often delays diagnosis and subsequent treatment. Here, we present a case of an infant with this condition who initially presented with triventricular hydrocephalus with Chiari I malformation. This alone is not a common presentation of this disease, and we present this case to highlight autosomal recessive osteopetrosis as a potential diagnosis in infants presenting with hydrocephalus and discuss the other associated symptoms, management, and prognosis of this condition.</AbstractText>The patient was a full-term infant with a routine newborn period. At 6 months, the infant had macrocephaly and frontal bossing with a bulging fontanelle. She was found to have hydrocephalus with moderate ventriculomegaly involving the third and lateral ventricles with an associated Chiari 1 malformation. The infant was asymptomatic at the time. The infant was promptly referred to neurosurgery and underwent an uncomplicated ventriculoperitoneal shunt placement. Post-operative X-rays showed increased density of the skull with other bone changes suggestive of autosomal recessive osteopetrosis. Subsequent lab work and imaging studies were consistent with this condition. The diagnosis was confirmed by genetic testing, and the patient has undergone treatment with hematopoietic stem cell transplant.</AbstractText>Hydrocephalus is a common feature of this condition, typically seen in conjunction with other systemic symptoms and laboratory findings. Our patient had a limited initial presentation of triventricular hydrocephalus with Chiari I malformation and was otherwise clinically asymptomatic. There is limited literature of such a presentation, and we highlight this case to increase awareness, as timely diagnosis of these patients is critical for treatment and future outcomes.</AbstractText>© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</CopyrightInformation> |
2,331,017 | Arnold-Chiari Malformation: Core Concepts. | Arnold-Chiari malformation (ACM), a defect that involves downward displacement of the hindbrain and herniation of the cerebellar vermis, tonsils, pons, medulla, and fourth ventricle through the foramen magnum, is the most complex of the 4 types of Chiari malformations. Unique to the other types of Chiari malformations, approximately 95 percent of infants with ACM also present with an associated myelomeningocele (MMC), the most severe form of spina bifida. Among affected infants, those with symptomatic comorbidities incur a significantly higher morbidity and mortality risk. Prompt identification and diagnosis of ACM, as well as evidence-based postnatal and postsurgical nursing and medical care, is critical. Early surgical intervention can repair an existing MMC and restore proper cerebrospinal fluid circulation, which can dramatically improve patient outcomes and quality of life, and reduce disease and health care burden. |
2,331,018 | Comparison of the histology and stiffness of ventricles in Anura of different habitats. | Vertebrate hearts have undergone marked morphological and structural changes to adapt to different environments and lifestyles as part of the evolutionary process. Amphibians were the first vertebrates to migrate to land. Transition from aquatic to terrestrial environments required the ability to circulate blood against the force of gravity. In this study, we investigated the passive mechanical properties and histology of the ventricles of three species of Anura (frogs and toads) from different habitats, Xenopus laevis (aquatic), Pelophylax nigromaculatus (semiaquatic), and Bufo japonicus formosus (terrestrial). Pressure-loading tests demonstrated stiffer ventricles of P. nigromaculatus and B. j. formosus compared X. laevis ventricles. Histological analysis revealed a remarkable difference in the structure of cardiac tissue: thickening of the compact myocardium layer of P. nigromaculatus and B. j. formosus and enrichment of the collagen fibers of B. j. formosus. The amount of collagen fibers differed among the species, as quantitatively confirmed by second-harmonic generation light microscopy. No significant difference was observed in cardiomyocytes isolated from each animal, and the sarcomere length was almost the same. The results indicate that the ventricles of Anura stiffen during adaptation to life on land. |
2,331,019 | Sex differences in cardiovascular adaptations in recreational marathon runners. | There are well-established sex differences in central hemodynamic and cardiac adaptations to endurance exercise; however, controversial evidence suggests that excessive endurance exercise may be related to detrimental cardiovascular adaptations in marathoners.</AbstractText>To examine left ventricle (LV) structure, LV function, 24-h central hemodynamics and ventricular-vascular coupling in male and female marathoners and recreationally active adults.</AbstractText>52 marathoners (41 ± 5 years, n = 28 female, completed 6 ± 1 marathons/3 years) and 49 recreationally active controls (42 ± 5 years, n = 25 female) participated in the study. Three-Dimensional Echocardiography (3DE) was used to measure LV mass index and LV longitudinal (LS) circumferential (CS), area (AS), and radial strain (RS). An ambulatory blood pressure (BP) cuff was used to measure 24-h central hemodynamics (BP, pulse wave velocity, PWV, wave reflection index, RIx). Hemodynamic and 3DE measures were combined to derive the ratio of arterial elastance (Ea) to ventricular elastance (Elv) as a global measure of ventricular-vascular coupling.</AbstractText>There were no sex or group differences in LS, CS, AS, and RS (p > 0.05). Females marathoners had similar aortic BP (116 ± 9 vs. 113 ± 1 mmHg), and PWV (5.9 ± 0.5 vs. 5.9 ± 1.1 m/s) compared to female controls but lower aSBP (116 ± 9 vs. 131 ± 10 mmHg) and PWV (5.9 ± 0.5 vs. 6.2 ± 0.5 m/s) compared to male marathoners (p < 0.05). Female marathoners had lower Ea/Elv than female controls (0.67 ± 0.20 vs. 0.93 ± 0.36) and male marathoners (0.67 ± 0.20 vs. 0.85 ± 0.42, p < 0.05).</AbstractText>Women that have completed multiple marathons do not have reduced LV function or increased aortic stiffness and may have better ventricular-vascular coupling compared to male marathoners and their female untrained counterparts.</AbstractText>© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</CopyrightInformation> |
2,331,020 | Case Report: Congenital Coronary Artery Ring With Single Left Coronary Ostium and Fistula: A Previously Unreported Anatomy. | <b>Background:</b> Single coronary ostium concomitant with coronary artery fistula is a very rare congenital anomaly. Apart from that, the combination of a closed loop of the coronary artery has never been reported. <b>Case presentation:</b> Herein, we present a 7-year-old girl diagnosed as single left coronary ostium with a giant coronary trunk, coronary artery to right ventricle fistula, and coronary artery ring. The coronary fistula was surgically ligated with off-pump strategy and the patient discharged on postoperative day 5 and free of symptoms during the 3 years of follow-up. <b>Conclusion:</b> To our knowledge, the presented congenital coronary anomaly is the first to be reported in the literature with the name of congenital coronary artery ring with single left coronary ostium and fistula. |
2,331,021 | Association of Maternal Gestational Weight Gain With Left Ventricle Geometry and Function in Offspring at 4 Years of Age: A Prospective Birth Cohort Study. | <b>Background:</b> Maternal gestational weight gain (GWG) may be associated with cardiovascular diseases in the offspring from childhood to adulthood. We aimed to investigate the association between maternal GWG and the left ventricle (LV) geometry and function in the offspring, and explore the influence of the intrauterine environment on early childhood cardiac change. <b>Methods:</b> Data of 981 mother-offspring pairs from the Shanghai Birth Cohort was used. Maternal pre-pregnancy weight and height, weight in the first trimester (≤ 12 weeks), and before delivery were measured. The echocardiography, blood pressure, and anthropometry assessment were evaluated in the offspring at 4 years of age. <b>Results:</b> Interventricular septal thickness during diastole had a significantly positive correlation with total GWG [β = 0.009, (0.001, 0.017)]. In the second and third trimesters, LV mass index [β = 0.149, (0.015,0.282)], interventricular septal thickness in systole [β = 0.027, (0.011,0.043)], and in diastole [β = 0.014, (0.005,0.023)] were positively associated with GWG. The risks of eccentric [OR = 1.115, (1.232, 1.010)] and concentric hypertrophy [OR = 1.133, (1.259,1.018)] increased with the elevation of maternal GWG. <b>Conclusions:</b> This study suggested that the excessive maternal GWG was associated with the thickening of the interventricular septum in the offspring, especially during the second and third trimesters. Excessive GWG in the second and third trimesters was a risk factor for LV eccentric and concentric hypertrophy in the offspring. |
2,331,022 | Acute Headache Due to Intracerebral Hemorrhage Secondary to Brain Metastases. | Intracerebral hemorrhage (ICH) is a relatively common condition seen throughout the world, with the vast majority of cases referring to primary ICH. However, secondary ICH from other underlying conditions is also possible. In the present case, the patient presented with severe headaches. An initial computed tomography (CT) was taken which showed hyperdense regions in both the occipital lobe and right lateral ventricle. The patient was hypertensive upon arrival, so medication was given to lower his blood pressure. Due to the patient's history of hypertension, it was believed to be a case of primary ICH caused by high blood pressure, but because of the odd positioning of the hemorrhaging, it was recommended for magnetic resonance imaging (MRI) and angiography (MRA) to be taken. Using the MRI and MRA, it was found out that growing nodes were responsible for the hypodense regions on the CT. Considering the patient's history of renal cell carcinoma metastasizing to the abdomen and lungs, the nodes were diagnosed as brain metastasis (BM) developed from the patient's past kidney cancer. Considering the hemorrhaging locations in the brain, it was concluded that the ICH was secondary to BM. After consulting neurosurgery and hematology, the patient was discharged to his family. Although not very prevalent in cases of ICH, BM is a cause that can not be overlooked. Sometimes initial imaging does not reveal such an underlying source. It is always important to pay close attention to the characteristics of the ICH so that it is possible to determine the true reason for the hemorrhage. |
2,331,023 | Third ventricle colloid cysts: An endoscopic case series emphasizing technical variations. | Colloid cyst treatment with purely endoscopic surgery is considered to be safe and effective. Complete capsule removal for gross total resection is usually recommended to prevent recurrence but may not always be safely feasible. Our objective was to assess the results of endoscopic surgery using mainly aspiration and coagulation without complete capsule resection and discuss the rationale for the procedure.</AbstractText>A retrospective review was conducted of 45 consecutive symptomatic patients with third ventricle colloid cysts that were surgically treated with purely endoscopic surgery from 1997 to 2018.</AbstractText>Mean age was 35.4 years. Male-to-female ratio was 1:1. Clinical presentation included predominantly headache (80%). Transforaminal was the most used route (71.1%) followed by transeptal (24.5%) and interforniceal (4.4%). Capsule was intentionally not removed in 42 patients (93.3%) and cyst remnants were absent on postoperative MRI in 36 (85%). Mild complications occurred in 8 patients (17.8%). Surgery was statistically associated with cyst volume and ventricular size reduction. There were no serious complications, shunts or deaths. Follow-up did not show any recurrence or remnant growth that needed further treatment.</AbstractText>Gross total resection may not be the main objective for every situation. Subtotal resection without capsule removal seems to be safer while preserving good results, especially in a limited resource environment. Remnants left behind should be followed but tend to remain clinically asymptomatic for the most part. Surgical planning allows the surgeon to choose among the different resection routes and techniques available. Decisions are predominantly based on preoperative imaging and intraoperative findings.</AbstractText>Copyright: © 2021 Surgical Neurology International.</CopyrightInformation> |
2,331,024 | Cardiovascular Properties of the Androgen-Induced PCOS Model in Rats: The Role of Oxidative Stress. | Polycystic ovary syndrome (PCOS) is a multifaced reproductive endocrinopathy affecting 6-20% of women of childbearing age. It was previously shown that women with PCOS have an increased risk of cardiovascular (CV) diseases. The aim of this study was to evaluate the cardiodynamic parameters of isolated rats' hearts, blood pressure levels, and histomorphological changes in the heart tissue following the androgen-induced PCOS model in rats and the role of oxidative stress in the development of these CV properties of PCOS. 21-day-old female rats (<i>n</i> = 12) were divided into control and PCOS groups. PCOS was induced by administration of testosterone enanthate (1 mg/kg BW, daily) during 35 days. During the autoregulation protocol (40-120 mmHg) on the Langendorff apparatus, ex vivo cardiodynamic parameters of retrogradely perfused hearts showed enhanced contractile function and increased lusitropic effects in the left ventricle (LV) in PCOS rats. Systolic and diastolic pressures in LV were elevated at all perfusion pressure values. Systemic arterial systolic blood pressure showed borderline elevation, while mean arterial blood pressure was significantly higher in PCOS rats. Histological evaluation of heart tissue depicted hypertrophic (8.3%) alterations in LV cardiomyocytes and increase (7.3%) in LV wall thickness. Oxidative stress parameters were altered in systemic circulation, coronary venous effluent (CVE), and heart tissue. Levels of superoxide dismutase and reduced glutathione were decreased in blood and heart tissue, while catalase activity was not altered. Degree of lipid peroxidation was increased in circulation as well as heart tissue. Increased levels of O<sub>2</sub> <sup>-</sup> in CVE indicated the cardiotoxic effects in the rat PCOS model. The mentioned alterations of oxidative stress parameters in the blood, CVE, and heart could be recommended as potential contributors underlying the development of CV risk in PCOS women. |
2,331,025 | Endoscopic Third Ventriculostomy and Endoscopic Intracranial Cyst Fenestration in an Outpatient Ambulatory Surgery Center Yields Reduced Cost But Equal Efficacy and Safety Compared with Surgery in the Hospital. | A transition is underway in neurosurgery to perform relatively safe surgeries outpatient, often at ambulatory surgery centers (ASC). We sought to evaluate whether simple intracranial endoscopic procedures such as third ventriculostomy and cyst fenestration can be safely and effectively performed at an ASC, while comparing costs with the hospital.</AbstractText>A retrospective chart review was performed for patients who underwent elective intracranial neuroendoscopic (NE) intervention at either a quaternary hospital or an affiliated ASC between August 2014 and September 2017. Groups were compared on length of stay, perioperative and 30-day morbidity, as well as clinical outcome at last follow-up. The total cost for these procedures were compared in relative units between all ASC cases and a small subset of hospital cases.</AbstractText>In total, 16 NE operations performed at the ASC (mean patient age 29.8 years) and 37 at the hospital (mean age 15.4 years) with average length of stay of 3.5 hours and 23.1 hours respectively (P < 0.05). There were no acute complications in either cohort or morbid events requiring hospitalization within 30 days. Surgical success was noted for 75% of the ASC patients and 73% of the hospital cohort. The mean cost of 5 randomly selected hospital operations with same-day discharge and 5 with overnight stay was 3.4 and 4.1 times that of the ASC cohort, respectively (P < 0.05).</AbstractText>Elective endoscopic third ventriculostomy and other simple NE procedures can be safely and effectively performed at an ASC for appropriate patients with significantly reduced cost compared with the hospital.</AbstractText>Copyright © 2021 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,331,026 | A finite element model of the cardiac ventricles with coupled circulation: Biventricular mesh generation with hexahedral elements, airbags and a functional mockup interface to the circulation. | Finite element (FE) mechanics models of the heart are becoming more sophisticated. However, there is lack of consensus about optimal element type and coupling of FE models to the circulation. We describe biventricular (left (LV) and right (RV) ventricles) FE mechanics model creation using hexahedral elements, airbags and a functional mockup interface (FMI) to lumped-parameter models of the circulation.</AbstractText>Cardiac MRI (CMR) was performed in two healthy volunteers and a single patient with ischemic heart disease (IHD). CMR images were segmented and surfaced, meshing with hexahedral elements was performed with a "thin butterfly with septum" topology. LV and RV inflow and outflow airbags were coupled to lumped-parameter circulation models with an FMI interface. Pulmonary constriction (PAC) and vena cava occlusion (VCO) were simulated and end-systolic pressure-volume relations (ESPVR) were calculated.</AbstractText>Mesh construction was prompt with representative contouring and mesh adjustment requiring 32 and 26 min Respectively. The numbers of elements ranged from 4104 to 5184 with a representative Jacobian of 1.0026 ± 0.4531. Agreement between CMR-based surfaces and mesh was excellent with root-mean-squared error of 0.589 ± 0.321 mm. The LV ESPVR slope was 3.37 ± 0.09 in volunteers but 2.74 in the IHD patient. The effect of PAC and VCO on LV ESPVR was consistent with ventricular interaction (p = 0.0286).</AbstractText>Successful co-simulation using a biventricular FE mechanics model with hexahedral elements, airbags and an FMI interface to lumped-parameter model of the circulation was demonstrated. Future studies will include comparison of element type and study of cardiovascular pathologies and device therapies.</AbstractText>Copyright © 2021. Published by Elsevier Ltd.</CopyrightInformation> |
2,331,027 | Mean Evan's Index among Patients with Normal Computed Tomography Scan visiting Radiology Department in a Tertiary Care Centre of Nepal: A Descriptive Cross-sectional Study. | Evan's index is useful to objectively see if ventricles size is abnormal especially in borderline cases of hydrocephalus. Studying ventricular size in CT scan is essential in every pathology of the brain. Use of objective parameters to define hydrocephalus helps us not only to diagnose a case but also follow up the case following treatment. The aim of this study was to find out the mean even index among patients visiting the department of radiology of a tertiary care hospital.</AbstractText>A descriptive cross-sectional study was conducted at a tertiary care hospital from 1st january 2020 to 31st December 2020. Ethical clearance was obtained from the Institutional Review Committee of Upendra Devkota Memorial Neurological and Allied Sciences (reference number: 116/2021). Computed tomography scans were done for various reasons in the hospital over a one year period and reported normal by the radiologists were included in the study. Convenient sampling was done. Statistical analysis was done using Statistical Package for the Social Sciences. Point estimate at 95% Confidence Interval was calculated along with mean and standard deviation for continuous data.</AbstractText>In this study, among the 216 cases, the mean Evan's index was found to be 0.20±0.04.</AbstractText>The mean evan's index in our study population was lower than the normal cut-off value.</AbstractText> |
2,331,028 | Vagus nerve stimulation mediates microglia M1/2 polarization via inhibition of TLR4 pathway after ischemic stroke. | Ischemic stroke is the leading cause of death and disability. Microglia are polarized toward the proinflammatory M1 phenotype and neuroprotective M2 phenotype after stroke and play an important role in the pathological process of ischemic stroke. Emerging research suggests that vagus nerve stimulation (VNS) can mediate microglia polarization after ischemic stroke and may serve as a potential treatment for ischemic stroke. However, the mechanism by which VNS mediates microglia polarization remains unclear. In this study, we aimed to investigate the underlying mechanism. Sprague-Dawley rats were randomly divided into the sham, ischemic stroke, ischemic stroke + VNS, ischemic stroke + VNS + lentivirus (LV)-TLR4 and ischemic stroke + VNS + LV-CON groups. LV was injected into the lateral ventricles of the rats 14 days before ischemic stroke surgery, and VNS was administered after 30 min of occlusion. We assessed the infarct volume, neurological scores, the TLR4/MyD88/NF-κB protein level and microglia polarization after 3 days of reperfusion. Our results revealed that VNS can promote M2 microglia polarization and inhibit M1 microglia polarization to alleviate brain injury via inhibition of the TLR4/MyD88/NF-κB pathway in microglia in the acute stage of stroke. |
2,331,029 | The protective effects of neural stem cells and neural stem cells-conditioned medium against inflammation-induced prenatal brain injury. | Intrauterine inflammation affects fetal development of the nervous system and may cause prenatal brain injury in offspring. Previously, neural stem cells have been extensively used as a therapeutic choice for nervous system diseases. Recently, the therapeutic ability of conditioned medium, harvested from cultured stem cells, has captured the attention of researchers in the field. Our study aimed to compare the therapeutic effect of neural stem cells (NSCs) or NSC-conditioned medium (NSC-CM) after prenatal brain injury. The animal model was induced by intraperitoneal injection of lipopolysaccharide into the pregnant mice and NSCs or NSC-CM were transplanted into the lateral ventricle of embryos in treatment groups. Inflammation and apoptosis were evaluated postpartum in offspring via measuring the expression of NLRP3 gene and protein, the expression and the activity of caspase-3, and the expression of pro-inflammatory cytokines by real-time PCR, immunohistochemistry, western blotting, ELISA, and colorimetric assay kit. A rotarod test was performed for motor function evaluation. Data showed that although NSC-CM fought against the inflammation and apoptosis and improved the motor function, NSCs acted more efficiently. In conclusion, the results of our study contend that NSCs have a better therapeutic effect than CM in prenatal brain injury. |
2,331,030 | Percutaneous Transfontanellar External Ventricular Drainage in an Extremely Low Birth Weight Infant: 2-Dimensional Operative Video. | Intraventricular hemorrhage and the subsequent development of posthemorrhagic hydrocephalus (PHH) is one of the most serious complication of prematurity, especially in extremely low birth weight infants.<sup>1</sup> Neurodevelopmental delay, epilepsy, and severe cognitive impairment represent common sequelae of PHH.<sup>2</sup><sup>,</sup><sup>3</sup> A ventriculoperitoneal shunt insertion in such premature infants is associated with higher rates of skin erosion, infection, and shunt failure.<sup>4</sup> One therapeutic option is represented by the use of temporary cerebrospinal fluid diversion procedures (such as external ventricular drainage, subcutaneous reservoir, and ventriculosubgaleal shunt) to gain time avoiding the PHH secondary damages.<sup>5</sup><sup>,</sup><sup>6</sup> An extremely low birth weight (birth weight = 653 g) infant at 24 + 4 gestational age weeks presented with a grade III intraventricular hemorrhage and periventricular hemorrhagic infarction 5 days after birth. Serial transfontanellar ultrasound disclosed a progressive PHH. Progressive symptomatic PHH, pulmonary hemodynamic instability, and suboptimal general prematurity conditions were the main factors that led to plan a percutaneous transfontanellar ultrasound-guided external ventricular drainage at the neonatal intensive care unit. The illustrated procedure represents a bedside minimally invasive, effective, reversible, and sparing-time choice alternative to other temporary cerebrospinal fluid diversion techniques. This edited, 2-dimensional operative video highlights the key surgical steps of the proposed procedure (Video 1). All relevant patient identifiers have been removed from the video. Nevertheless, the parent's consent was obtained regarding the procedure, video recording, and redistribution for educational purposes. |
2,331,031 | Patient selection for LIVE therapy: From clinical indications to multimodality imaging individual case planning. | Less Invasive Ventricular Enhancement (LIVE) with Revivent TC is an innovative therapy for symptomatic ischemic heart failure (HF). It is designed to reconstruct a negatively remodeled left ventricle (LV) after an anterior myocardial infarction (MI) by plication of the scar tissue. Its indications are specific, and as with any other structural heart intervention, the success of the procedure starts with appropriate patient selection. We aim to present the indications of the technique, crucial aspects in patient selection, and individual case planning approach.</AbstractText>After clinical evaluation, transthoracic echocardiography is the first imaging modality to be performed in a potential candidate for the therapy. However, definitive indication and detailed case planning rely on late gadolinium-enhanced cardiac magnetic resonance imaging or multiphasic contrast-enhanced cardiac computed tomography. These imaging modalities also assist with relative or absolute contra-indications for the procedure. Individual assessment is done to tailor the procedure to the specifics of the LV anatomy and location of the myocardial scar.</AbstractText>LIVE procedure is a unique intervention to treat symptomatic HF and ischemic cardiomyopathy after anterior MI. It is a highly customizable intervention that allows a patient-tailored approach, based on multimodality imaging assessment and planification.</AbstractText>© 2021 Wiley Periodicals LLC.</CopyrightInformation> |
2,331,032 | Right ventricular perforation, pneumothorax, and a pneumatocele by a pacemaker lead: a case report. | Perforation of the right ventricle by a pacemaker lead is a rare and potentially life-threatening complication. We present a patient who developed right ventricular perforation, pneumothorax, and a cyst and underwent partial lung resection.</AbstractText>A 94-year-old woman was diagnosed with sick sinus syndrome and underwent a dual-chamber permanent pacemaker implantation. The next day, pacing failed and chest radiography showed that the right ventricular lead was outside the cardiac silhouette. Computed tomography revealed that the lead had perforated the right ventricular apex, causing a left-sided pneumothorax and a cystic lesion at the site of pulmonary injury by the pacemaker lead. The patient underwent lung resection and a right ventricular lead extraction. Pathological analysis revealed the cystic lesion to be an acute pneumatocele.</AbstractText>Pneumothorax and pneumatocele associated with right ventricular pacemaker lead perforation is extremely rare. In our case, a radical surgical intervention provided an excellent outcome.</AbstractText>© 2021. The Author(s).</CopyrightInformation> |
2,331,033 | Electrophysiological Effects of the Transient Receptor Potential Melastatin 4 Channel Inhibitor (4-Chloro-2-(2-chlorophenoxy)acetamido) Benzoic Acid (CBA) in Canine Left Ventricular Cardiomyocytes. | Transient receptor potential melastatin 4 (TRPM4) plays an important role in many tissues, including pacemaker and conductive tissues of the heart, but much less is known about its electrophysiological role in ventricular myocytes. Our earlier results showed the lack of selectivity of 9-phenanthrol, so CBA ((4-chloro-2-(2-chlorophenoxy)acetamido) benzoic acid) was chosen as a new, potentially selective inhibitor. Goal: Our aim was to elucidate the effect and selectivity of CBA in canine left ventricular cardiomyocytes and to study the expression of TRPM4 in the canine heart. Experiments were carried out in enzymatically isolated canine left ventricular cardiomyocytes. Ionic currents were recorded with an action potential (AP) voltage-clamp technique in whole-cell configuration at 37 °C. An amount of 10 mM BAPTA was used in the pipette solution to exclude the potential activation of TRPM4 channels. AP was recorded with conventional sharp microelectrodes. CBA was used in 10 µM concentrations. Expression of TRPM4 protein in the heart was studied by Western blot. TRPM4 protein was expressed in the wall of all four chambers of the canine heart as well as in samples prepared from isolated left ventricular cells. CBA induced an approximately 9% reduction in AP duration measured at 75% and 90% of repolarization and decreased the short-term variability of APD<sub>90</sub>. Moreover, AP amplitude was increased and the maximal rates of phase 0 and 1 were reduced by the drug. In AP clamp measurements, CBA-sensitive current contained a short, early outward and mainly a long, inward current. Transient outward potassium current (I<sub>to</sub>) and late sodium current (I<sub>Na,L</sub>) were reduced by approximately 20% and 47%, respectively, in the presence of CBA, while L-type calcium and inward rectifier potassium currents were not affected. These effects of CBA were largely reversible upon washout. Based on our results, the CBA induced reduction of phase-1 slope and the slight increase of AP amplitude could have been due to the inhibition of I<sub>to</sub>. The tendency for AP shortening can be explained by the inhibition of inward currents seen in AP-clamp recordings during the plateau phase. This inward current reduced by CBA is possibly I<sub>Na,L</sub>, therefore, CBA is not entirely selective for TRPM4 channels. As a consequence, similarly to 9-phenanthrol, it cannot be used to test the contribution of TRPM4 channels to cardiac electrophysiology in ventricular cells, or at least caution must be applied. |
2,331,034 | Combined Endoscopic Transsphenoidal and Tubular Retractor-Assisted Transventricular Approach for Giant Pituitary Adenomas. | Surgical resection remains the standard treatment for most giant pituitary adenomas (GPAs). The selected surgical approach for these complex lesions depends mainly on their extension. Single approaches may be limited in some cases presenting with invasion into multiple compartments, thereby limiting extent of resection.</AbstractText>We report a series of patients with GPA operated on through a combined approach involving an endoscopic endonasal transsphenoidal approach and a tubular retractor-assisted transventricular approach, describing the technique, its indications, limitations, and outcomes. Baseline and postoperative clinical, functional, and morphologic variables were documented up until each patient's last follow-up visit.</AbstractText>Five patients harboring tumors extending into the third and lateral ventricles were included. Mean extent of resection was 94.6%. Mean follow-up was 39.4 months. One patient presented with a growth hormone-secreting GPA, who achieved remission after repeat resection during follow-up. There were no intraoperative complications, and 1 patient required reoperation for cerebrospinal fluid leak repair. One patient received adjuvant radiotherapy, and 3 patients remained stable requiring no additional treatment. All patients maintained an adequate postoperative functional status.</AbstractText>The combined approach herein described may be a safe and effective option for some patients with GPAs extending into the third and lateral ventricles. An adequate patient selection is mandatory to exploit the benefits of each individual approach.</AbstractText>Copyright © 2021 Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,331,035 | Claudin-5a knockdown attenuates blood-neural barrier in zebrafish. | Mammalian claudin-5 (cldn5), a zebrafish cldn5a homolog, is essential to blood-brain barrier (BBB) integrity. Previously, the existence of an endothelial tight junction-based BBB with cldn5a expression in the cerebral microvessels was reported in zebrafish. However, the role of cldn5a in the cerebral microvessels of developing zebrafish has not been elucidated. Here, we further investigated the functional integrity of cldn5a in developing zebrafish by injecting cldn5a morpholinos. At 7 days post-fertilization, cldn5a immunoreactivity was detected on the brain surface, ventricular ependyma, and cerebral mircovessels but disappeared following cldna5a knockdown. Cldn5a morphants showed size-selective leakage of tracers through the BBB and downregulated expression of glucose transporter 1 (glut1) in the cerebral microvessels. In addition, leakiness in the blood-cerebrospinal fluid barrier was observed, implying the overall abnormal development of blood-neural barriers. The results of our study suggest that cldn5a is required for building and maintaining the blood-neural barrier during zebrafish development. |
2,331,036 | Intracerebroventricular asprosin administration strongly stimulates hypothalamic-pituitary-testicular axis in rats. | Asprosin, a protein-based secretary product of white adipose tissue, stimulates appetite hepatic glucose production. It crosses blood-brain barrier and stimulates appetite center and causes sperm chemotaxis but exact role of this endogenous agent is not completely known. This study was conducted to investigate possible effects of central asprosin infusion on the hormones involved in the hypothalamic-pituitary-testicular (HPT) axis and sperm cells. Spraque Dawley male rats were divided into four groups; control, sham, low asprosin (34) and high asprosin (68 nM) groups, (n = 10 for each group). Control group remain intact while a brain infusion kit was placed in the lateral ventricles of the rats in the sham group (artificial cerebrospinal fluid) and asprosin (34 and 68 nM) was infused for 14 days. At the end of the experiment, the hypothalamus, blood, and epididymis tissues of the rats were collected. Gonadotropin-releasing hormone (GnRH) mRNA and tissue protein levels were determined in the hypothalamus tissue by RT-PCR and Western Blot methods. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels were examined using the ELISA method from blood samples and sperm cells were examined in the epididymis tissue. GnRH mRNA and protein expressions of asprosin administered groups were higher than control and sham groups (p < 0.05). Asprosin infusion was also found to increase serum FSH, LH, and testosterone levels (p < 0.05). In addition, sperm density, motility, and progressive movement were observed to increase in asprosin administered groups (p < 0.05). This study suggests that central asprosin stimulate the HPT axis and also epididymis tissue. Our results implicates potential role for asprosin in male infertility. |
2,331,037 | Progressive supranuclear palsy with marked ventricular dilatation mimicking normal pressure hydrocephalus. | Progressive supranuclear palsy (PSP) patients can show ventricular enlargement mimicking normal pressure hydrocephalus (NPH). The aim of this study was to distinguish PSP patients with marked ventricular dilatation (PSP-vd) from those with normal ventricular system and to evaluate the coexistence of NPH in PSP-vd patients.</AbstractText>One hundred three probable PSP patients, 18 definite NPH patients, and 41 control subjects were enrolled in the study. Evans index (EI) > 0.32 associated with callosal angle (CA) < 100° was used to identify PSP-vd patients. Automated ventricular volumetry (AVV) and Magnetic Resonance Hydrocephalic Index (MRHI) were performed on T1-weighted MR images to evaluate the presence of NPH in PSP-vd patients.</AbstractText>Twelve (11.6%) out of 103 PSP patients had both abnormal EI and CA values (PSP-vd). In two of these 12 patients, AVV and MRHI values suggested PSP + NPH. In the remaining 10 PSP-vd patients, AVV and MRHI values were higher than PSP patients with normal ventricular system and controls, but lower than PSP + NPH and NPH patients, suggesting a non-hydrocephalic ventricular enlargement.</AbstractText>Our study provides evidence that the combination of EI and CA biomarkers allowed to identify PSP patients with marked ventricular dilatation mimicking NPH. Only a few of these patients had PSP + NPH. Recognition of these PSP patients with enlarged ventricles can positively impact the care of this disease, helping clinicians to identify patients with PSP + NPH who could benefit from shunt procedure and avoid surgery in those with enlarged ventricles without NPH.</AbstractText>© 2021. Fondazione Società Italiana di Neurologia.</CopyrightInformation> |
2,331,038 | Application of plasma polymerized pyrrole nanoparticles to prevent or reduce de-differentiation of adult rat ventricular cardiomyocytes. | Cardiovascular diseases are the leading cause of death in the world, cell therapies have been shown to recover cardiac function in animal models. Biomaterials used as scaffolds can solve some of the problems that cell therapies currently have, plasma polymerized pyrrole (PPPy) is a biomaterial that has been shown to promote cell adhesion and survival. The present research aimed to study PPPy nanoparticles (PPPyN) interaction with adult rat ventricular cardiomyocytes (ARVC), to explore whether PPPyN could be employed as a nanoscaffold and develop cardiac microtissues. PPPyN with a mean diameter of 330 nm were obtained, the infrared spectrum showed that some pyrrole rings are fragmented and that some fragments of the ring can be dehydrogenated during plasma synthesis, it also showed the presence of amino groups in the structure of PPPyN. PPPyN had a significant impact on the ARVC´s shape, delaying dedifferentiation, necrosis, and apoptosis processes, moreover, the cardiomyocytes formed cell aggregates up to 1.12 mm<sup>2</sup> with some aligned cardiomyocytes and generated fibers on its surface similar to cardiac extracellular matrix. PPPyN served as a scaffold for adult ARVC. Our results indicate that PPPyN-scaffold is a biomaterial that could have potential application in cardiac cell therapy (CCT). |
2,331,039 | Etiologic-sociodemographic assessment and comparison of dialysis modalities in pediatric Syrian migrants with chronic kidney disease. | Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are among the important causes of mortality and morbidity in childhood. Early diagnosis and treatment of the underlying primary disease may prevent most of CKD patients from progressing to ESRD. There is no study examining chronic kidney diseases and dialysis modalities in Syrian immigrant children. We aimed to retrospectively research the etiologic, sociodemographic, and clinical factors in CKD among Syrian refugee children, and at the same time, to compare the clinical characteristics of patients with ESRD on peritoneal dialysis and hemodialysis.</AbstractText>Our study included a total of 79 pediatric Syrian patients aged from 2-16 years monitored at Hatay State Hospital pediatric nephrology clinic with diagnosis of various stages of CKD and with ESRD. Physical-demographic features and clinical-laboratory information were retrospectively screened.</AbstractText>The most common cause of CKD was congenital anomalies of the kidneys and urinary tracts (CAKUT) (37.9%). Other causes were urolitiasis (15.1%), nephrotic syndrome (10.1%), spina bifida (8.8%), hemolytic uremic syndrome (7.5%), and glomerulonephritis (7.5%). Twenty-five patients used hemodialysis due to bad living conditions. Only 2 of the patients with peritoneal dialysis were using automatic peritoneal dialysis (APD), with 5 using continuous ambulatory peritoneal dialysis (CAPD). Long-term complications like left ventricle hypertrophy and retinopathy were significantly higher among hemodialysis patients. There was no difference identified between the groups in terms of hypertension and sex.</AbstractText>Progression to ESRD due to preventable reasons is very frequent among CKD patients. For more effective use of peritoneal dialysis in pediatric patients, the responsibility of states must be improved.</AbstractText> |
2,331,040 | The co-administration effects of florfenicol and lasalocid on performance, biochemical and pathological parameters of muscle, heart, liver, kidney and sciatic nerve in broiler chickens. | The study aimed to examine the effect of simultaneous application of florfenicol and lasalocid on the performance and vital organ function of chickens. For this, 300 chicks were divided into four groups. Group one to three received florfenicol, lasalocid and lasalocid plus florfenicol, respectively. Group four as the control group received a basic diet without lasalocid or florfenicol. Lasalocid was used from 7 to 35 days old, continuously. Florfenicol was used at 21 days old for 5 days. The growth indices were measured at the end of each week. The chickens were euthanized at the ages of 28 and 35 days old after collecting blood samples with and without anticoagulants. The liver, heart, muscle, kidney and sciatic nerve were collected in formalin 10% for histopathological examination. The blood and serum samples were used to determine clinical pathologic and hematologic indices. The ratio of internal organs to body weight and ratio of the right ventricle to the total ventricles (RV/TV) of the heart was measured. Results showed, the use of lasalocid decreased feed conversion rate and triglyceride, and increased total protein. Simultaneous administration of lasalocid and florfenicol affected histopathology of the liver and heart and significantly increased creatine phosphokinase, uric acid and the ratio of RV/TV of heart. The eosinophil percentage in the chickens who received florfenicol plus lasalocid was significantly higher than chickens who received florfenicol alone (p < 0.05). In conclusion, it seems that simultaneous administration of the florfenicol and lasalocid induces side-effects especially on cardiac function and it is not recommended. |
2,331,041 | Rosette-Forming Glioneuronal Tumor in the Pineal Region: A Series of 6 Cases and Literature Review. | Resected lesions from the pineal region are rare specimens encountered by surgical pathologists, and their heterogeneity can pose significant diagnostic challenges. Here, we reviewed 221 pineal region lesions resected at New York-Presbyterian Hospital/Columbia University Irving Medical Center from 1994 to 2019 and found the most common entities to be pineal parenchymal tumors (25.3%), glial neoplasms (18.6%), and germ cell tumors (17.6%) in this predominantly adult cohort of patients. Six cases of a rare midline entity usually found exclusively in the fourth ventricle, the rosette-forming glioneuronal tumor, were identified. These tumors exhibit biphasic morphology, with a component resembling pilocytic astrocytoma admixed with variable numbers of small cells forming compact rosettes and perivascular pseudorosettes. Targeted sequencing revealed a 100% co-occurrence of novel and previously described genetic alterations in the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signaling pathways, suggesting a synergistic role in tumor formation. The most common recurrent mutation, PIK3CA H1047R, was identified in tumor cells forming rosettes and perivascular pseudorosettes. A review of the literature revealed 16 additional cases of rosette-forming glioneuronal tumors in the pineal region. Although rare, this distinctive low-grade tumor warrants consideration in the differential diagnosis of pineal region lesions. |
2,331,042 | Exploring Functional Differences between the Right and Left Ventricles to Better Understand Right Ventricular Dysfunction. | The right and left ventricles have traditionally been studied as individual entities. Furthermore, modifications found in diseased left ventricles are assumed to influence on right ventricle alterations, but the connection is poorly understood. In this review, we describe the differences between ventricles under physiological and pathological conditions. Understanding the mechanisms that differentiate both ventricles would facilitate a more effective use of therapeutics and broaden our knowledge of right ventricle (RV) dysfunction. RV failure is the strongest predictor of mortality in pulmonary arterial hypertension, but at present, there are no definitive therapies directly targeting RV failure. We further explore the current state of drugs and molecules that improve RV failure in experimental therapeutics and clinical trials to treat pulmonary arterial hypertension and provide evidence of their potential benefits in heart failure. |
2,331,043 | Identification of reference genes for gene expression studies among different developmental stages of murine hearts. | Real-time quantitative polymerase chain reaction (RT-qPCR) is a widely-used standard assay for assessing gene expression. RT-qPCR data requires reference genes for normalization to make the results comparable. Therefore, the selected reference gene should be highly stable in its expression throughout the experimental datasets. So far, reports about the optimal set of reference genes in murine left ventricle (LV) across embryonic and postnatal stages are few. The objective of our research was to identify the appropriate reference genes in murine LV among different developmental stages.</AbstractText>We investigated the gene expression profiles of 21 widely used housekeeping genes in murine LV from 7 different developmental stages (almost throughout the whole period of the mouse lifespan). The stabilities of the potential reference genes were evaluated by five methods: GeNorm, NormFinder, BestKeeper, Delta-Ct and RefFinder.</AbstractText>We proposed a set of reliable reference genes for normalization of RT-qPCR experimental data in different conditions. Furthermore, our results showed that 6 genes (18S, Hmbs, Ubc, Psmb4, Tfrc and Actb) are not recommended to be used as reference genes in murine LV development studies. The data also suggested that the Rplp0 gene might serve as an optimal reference gene in gene expression analysis.</AbstractText>Our study investigated the expression stability of the commonly used reference genes in process of LV development and maturation. We proposed a set of optimal reference genes that are suitable for accurate normalization of RT-qPCR data in specific conditions. Our findings may be helpful in future studies for investigating the gene expression patterns and mechanism of mammalian heart development.</AbstractText>© 2021. The Author(s).</CopyrightInformation> |
2,331,044 | Pseudolaric Acid B Attenuates High Salt Intake-Induced Hypertensive Left Ventricular Remodeling by Modulating Monocyte/Macrophage Phenotypes. | BACKGROUND Studies in ApoE knockout mice have shown that pseudolaric acid B (PB) can act as an immunomodulatory drug and attenuate atherosclerosis progression by modulating monocyte/macrophage phenotypes. Our previous study demonstrated that high salt intake could shift the phenotype of monocytes/macrophages to an inflammatory phenotype, and that this shift was related to hypertension and hypertensive left ventricular (LV) remodeling. However, no comprehensive assessment of the effects of PB on hypertensive LV remodeling has been conducted. MATERIAL AND METHODS In this study, RAW264.7 macrophages cultured with different concentrations of NaCl were used to investigate the modulating effects of PB on macrophage phenotype. Furthermore, N-nitro-L-arginine methyl ester hypertensive mice were used to investigate the modulating effects of PB on monocyte phenotype. LV remodeling was investigated by echocardiography. LV morphologic staining (for cardiomyocyte hypertrophy and collagen deposition) was performed at the time of sacrifice. RESULTS The results showed that PB significantly improved the viability of RAW264.7 cells, suppressed their phagocytic and migration abilities, and inhibited their phenotypic shift to M1 macrophages. In addition, the blood pressure of PB-treated mice was significantly decreased relative to that of control mice. Furthermore, after PB treatment, the percentage of Ly6Chi monocytes was significantly decreased while that of Ly6Clo monocytes was apparently increased. Moreover, PB preserved LV function and alleviated myocardial fibrosis and cardiomyocyte hypertrophy as measured at the end of the experimental period. The transfer of monocytes from PB-treated mice to hypertensive mice achieved the same effects. CONCLUSIONS Together, these findings indicate that PB exerts its protective effects on hypertensive LV remodeling by modulating monocyte/macrophage phenotypes and warrants further investigation. |
2,331,045 | Nandrolone combined with strenuous resistance training impairs myocardial proteome profile of rats. | We aimed to investigate the effects of high doses of nandrolone decanoate and resistance training (RT) on the proteomic profile of the left ventricle (LV) of rats, using a label-free quantitative approach. Male rats were randomized into four groups: untrained vehicle (UTV), trained vehicle (TV), untrained nandrolone (UTN), and trained nandrolone (TN). Rats were familiarized with the exercise training protocol (jump exercise) for one week. Jump-exercise was performed five days a week for 6 weeks, with 30 s of inter-set rest intervals. Nandrolone was administrated for 6 weeks (5 mg/kg, twice a week, via intramuscular). Systolic and diastolic arterial pressure and heart rate were measured 48 h post-training. LV was isolated and collagen content was measured. The expression of cardiac proteins was analyzed by ultra-efficiency liquid chromatography with mass spectrometry high / low collision energy (UPLC/MS<sup>E</sup>). Nandrolone and RT led to cardiac hypertrophy, even though high doses of nandrolone counteracted the RT-induced arterial pressures lowering. Nandrolone also affected the proteome profile negatively in LV of rats, including critical proteins related to biological processes (metabolism, oxidative stress, inflammation), structural function and membrane transporters. Our findings show physiological relevance since high doses of nandrolone induced detrimental effects on the proteome profile of heart tissue and hemodynamic parameters of rats. Furthermore, as nandrolone abuse has become increasingly common among recreational athletes and casual fitness enthusiasts, we consider that our findings have clinical relevance as well. |
2,331,046 | Fast myocardial T<sub>1ρ</sub> mapping in mice using k-space weighted image contrast and a Bloch simulation-optimized radial sampling pattern. | T1ρ</sub> dispersion quantification can potentially be used as a cardiac magnetic resonance index for sensitive detection of myocardial fibrosis without the need of contrast agents. However, dispersion quantification is still a major challenge, because T1ρ</sub> mapping for different spin lock amplitudes is a very time consuming process. This study aims to develop a fast and accurate T1ρ</sub> mapping sequence, which paves the way to cardiac T1ρ</sub> dispersion quantification within the limited measurement time of an in vivo study in small animals.</AbstractText>A radial spin lock sequence was developed using a Bloch simulation-optimized sampling pattern and a view-sharing method for image reconstruction. For validation, phantom measurements with a conventional sampling pattern and a gold standard sequence were compared to examine T1ρ</sub> quantification accuracy. The in vivo validation of T1ρ</sub> mapping was performed in N = 10 mice and in a reproduction study in a single animal, in which ten maps were acquired in direct succession. Finally, the feasibility of myocardial dispersion quantification was tested in one animal.</AbstractText>The Bloch simulation-based sampling shows considerably higher image quality as well as improved T1ρ</sub> quantification accuracy (+ 56%) and precision (+ 49%) compared to conventional sampling. Compared to the gold standard sequence, a mean deviation of - 0.46 ± 1.84% was observed. The in vivo measurements proved high reproducibility of myocardial T1ρ</sub> mapping. The mean T1ρ</sub> in the left ventricle was 39.5 ± 1.2 ms for different animals and the maximum deviation was 2.1% in the successive measurements. The myocardial T1ρ</sub> dispersion slope, which was measured for the first time in one animal, could be determined to be 4.76 ± 0.23 ms/kHz.</AbstractText>This new and fast T1ρ</sub> quantification technique enables high-resolution myocardial T1ρ</sub> mapping and even dispersion quantification within the limited time of an in vivo study and could, therefore, be a reliable tool for improved tissue characterization.</AbstractText>© 2021. The Author(s).</CopyrightInformation> |
2,331,047 | Longstanding overt ventriculomegaly in adults (LOVA) with patent aqueduct: surgical outcome and etiopathogenesis of a possibly distinct form of chronic hydrocephalus. | Longstanding overt ventriculomegaly in adults (LOVA) represents a form of chronic adulthood hydrocephalus with symptomatic manifestation in late adulthood. Based on the patency of the aqueduct, two different subcohorts of LOVA can be distinguished. Surgical treatments of this condition are also debated. Therefore, we analyzed preoperative characteristics and clinical outcome after different surgical treatments in a subgroup of LOVA patients with a patent aqueduct.</AbstractText>Eighteen LOVA patients with a patent aqueduct consecutively treated at our institution between July 2013 and December 2019 were analyzed for this study. Median age was 70 years. Preoperative radiological and clinical features, surgical procedures (ventriculo-peritoneal shunt or endoscopic third ventriculostomy), and outcomes were collected. Successful outcome was qualitatively defined as an improvement or a halt of progression of the presenting symptoms at follow-up, and quantitatively by changes in mRS and iNPHGS scales.</AbstractText>Twelve patients underwent an ETV as a primary treatment, while 6 underwent VPS. A total of 22.2% of them were lost to follow-up. Median follow-up time was 38 months. Six patients (66.7%) in the ETV cohort achieved a successful outcome after treatment, with a complication rate of 11.1%. Two patients underwent rescue VPS after ETV failure with a good outcome. Four patients (100%) underwent primary VPS and achieved a satisfactory outcome after treatment, with a reported complications rate of 25%.</AbstractText>LOVA with patent aqueduct represents, in our opinion, a distinct clinical form of chronic hydrocephalus. For this subgroup, as well as for other forms of LOVA, ETV remains an acceptable first-line treatment option considering the good results, and the low complication rate, obtained in those patients and the hypothesis that hydrocephalus is due to an "intracisternal" obstruction.</AbstractText>© 2021. The Author(s).</CopyrightInformation> |
2,331,048 | The stability of multifocal ventriculoperitoneal shunts with Y-connections. | Multifocal ventriculoperitoneal shunts with Y-connections (MVPS with Ys) are widely used in many centers when neuroendoscopic procedures on entrapped ventricles are not feasible; however, their use is not frequent. This study aimed to confirm the stability of an MVPS with Y and, for the first time, identify the factors that influence stability.</AbstractText>We studied 33 consecutive patients who underwent initial conversion to MVPS with Ys. The one-year overall shunt survival rate was calculated and compared with the historical outcome of single ventriculoperitoneal shunts (VPSs). The factors influencing the one-year overall shunt survival rate were also investigated. The one-year survival rate for proximal catheters in each location was further investigated, and the rates were compared among locations. The factors affecting proximal catheter survival were determined.</AbstractText>The one-year overall shunt survival rate of MVPS with Y was 70%, which was not much different from that of previously reported single VPSs, including our institution. We found no significant factor influencing overall shunt survival, but when an additional catheter was inserted into the fourth ventricle, the survival rate was exceptionally low at 40% (p = 0.21). When we investigated the one-year survival rate of each proximal catheter, we found that the location of the proximal catheter showed a certain trend toward significance (p = 0.07), especially in the case of the fourth ventricle, which had the lowest survival rate at 57% and an odds ratio of 15.64 (p = 0.013) in multivariate analysis. However, when the catheter was sufficiently inserted parallel to the brain stem using navigation, the survival was relatively well maintained (1,995 to 2,547 days).</AbstractText>The stability of MVPS with Y was similar to that of single VPSs. However, the malfunction rate of the proximal catheter inserted at the fourth ventricle in the Y-connection was higher than that at other locations. The transcerebellar vertical approach or transtentorial approach parallel to the brain stem may decrease the malfunction rate.</AbstractText>© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</CopyrightInformation> |
2,331,049 | Pharmacological inhibition of BAG3-HSP70 with the proposed cancer therapeutic JG-98 is toxic for cardiomyocytes. | The co-chaperone Bcl2-associated athanogene-3 (BAG3) maintains cellular protein quality control through the regulation of heat shock protein 70 (HSP70). Cancer cells manipulate BAG3-HSP70-regulated pathways for tumor initiation and proliferation, which has led to the development of promising small molecule therapies, such as JG-98, which inhibit the BAG3-HSP70 interaction and mitigate tumor growth. However, it is not known how these broad therapies impact cardiomyocytes, where the BAG3-HSP70 complex is a key regulator of protein turnover and contractility. Here, we show that JG-98 exposure is toxic in neonatal rat ventricular myocytes (NRVMs). Using immunofluorescence microscopy to assess cell death, we found that apoptosis increased in NRVMs treated with JG-98 doses as low as 10 nM. JG-98 treatment also reduced autophagy flux and altered expression of BAG3 and several binding partners involved in BAG3-dependent autophagy, including SYNPO2 and HSPB8. We next assessed protein half-life with disruption of the BAG3-HSP70 complex by treating with JG-98 in the presence of cycloheximide and found BAG3, HSPB5, and HSPB8 half-lives were reduced, indicating that complex formation with HSP70 is important for their stability. Next, we assessed sarcomere structure using super-resolution microscopy and found that disrupting the interaction with HSP70 leads to sarcomere structural disintegration. To determine whether the effects of JG-98 could be mitigated by pharmacological autophagy induction, we cotreated NRVMs with rapamycin, which partially reduced the extent of apoptosis and sarcomere disarray. Finally, we investigated whether the effects of JG-98 extended to skeletal myocytes using C2C12 myotubes and found again increased apoptosis and reduced autophagic flux. Together, our data suggest that nonspecific targeting of the BAG3-HSP70 complex to treat cancer may be detrimental for cardiac and skeletal myocytes. |
2,331,050 | [Analysis of DNM1L gene variant in a case of fatal encephalopathy caused by mitochondrial peroxidase division deficiency]. | To explore the clinical features and disease-causing variants of a pediatric patient with fatal encephalopathy caused by mitochondrial peroxidase division deficiency, to identify the possible genetic causes of the disease and provide a basis for clinical diagnosis.</AbstractText>A child with fatal encephalopathy caused by mitochondrial peroxidase division deficiency in West China Second Hospital of Sichuan University was selected. The clinical manifestations, laboratory findings and disease-causing variant were analyzed.</AbstractText>The main clinical symptoms of the patient were fever, headache and vomiting, followed by drug refractory epilepsy and progressive disturbance of consciousness. MRI showed deepening of sulcus, dilatation of bilateral ventricles, and multiple patch-like abnormal signals in paraventricular white matter, semioval center and subcortical white matter of bilateral frontal lobe. Gene detection showed a heterozygous missense variant c.1207C>T(p.Arg403Cys) in DNM1L, according to the American College of Medical Genetics and Genomics classification standards and guidelines for genetic variants, this variant was predicted to be pathogenic(PS1+PS2+PM2+PP3). After treated with gamma globulin, glucocorticoid, "mitochondrial cocktail therapy" and anti-epilepsy drugs, the condition of the patient was getting better, seizure attacks reduced and consciousness level improved.</AbstractText>The c.1207C>T variant in DNM1L gene may be the disease-causing variant for the patient, and the result of genetic testing provides a basis for the clinical diagnosis in this case.</AbstractText> |
2,331,051 | Global longitudinal strain in heart transplantation recipients using different vendors: reliability and validity in a tertiary hospital in Colombia. | Global Longitudinal Strain (GLS) is a useful tool to follow-up heart transplant (HT) recipients. Important inter-vendor variability of GLS measurements has been reported in healthy subjects and different conditions, but there is still limited evidence among HT patients. We assessed the reliability and validity of GLS using two vendors (General Electric and Philips) in a group of consecutive and stable adult HT recipients. Patients underwent two concurrent GLS analyses during their echocardiographic follow-up. We evaluated GLS inter-vendor reliability using Bland-Altman's limits of agreement (LOA) plots, computing its coverage probability (CP) and the intraclass correlation coefficient (ICC). Validity was assessed though receiver operating characteristics (ROC) curves, predictive values, sensitivity and specificity of GLS for each vendor to detect a normal left ventricle function. 78 pairs of GLS studies in 53 stable HT patients were analyzed. We observed a modest inter-vendor reliability with a broad LOA (less than 50% of values falling out our CP of 2% and an ICC of 0.49). ROC analyses (areas under the curve of 0.824 Vs. 0.631, p < 0.05) and diagnosis test indices (Sensitivity of 0.73 Vs. 0.64; and Specificity of 0.79 Vs. 0.50) favored GE over Philips. Inter-vendor variability for GLS analysis exceeded clinically acceptable limits in HT recipients. GLS from GE software seemed to show higher validity as compared to Philips'. The present study provides evidence to consider caution for the interpretation of GLS for clinical management in the follow-up of HT patients, especially when GLS is measured by different vendors. |
2,331,052 | SARS-CoV-2 infection of the central nervous system in a 14-month-old child: A case report of a complete autopsy. | Neurological and other systemic complications occur in adults with severe COVID-19. Here we describe SARS-CoV-2 infection complicated by neuroinvasion in the post-mortem</i> tissues of a child.</AbstractText>We performed a complete autopsy of a 14-month-old child who died of COVID-19 pneumonitis. Histological sections of multiple organs were stained with haematoxylin and eosin. Luxol fast blue staining for myelin and immunohistochemistry were performed in selected areas of the brain. The presence of SARS-CoV-2 was investigated by immunostaining with anti-spike protein antibody and by RT-qPCR.</AbstractText>Lesions included microthrombosis, pulmonary congestion, interstitial oedema, lymphocytic infiltrates, bronchiolar injury, collapsed alveolar spaces, cortical atrophy, and severe neuronal loss. SARS-CoV-2 staining was observed along the apical region of the choroid plexus (ChP) epithelium and in ependymal cells of the lateral ventricle, but was restricted to ChP capillaries and vessels in some regions. SARS-CoV-2 infection of brain tissue was confirmed by RT-qPCR in fragments of the ChP, lateral ventricle, and cortex.</AbstractText>Our results show multisystemic histopathological alterations caused by SARS-CoV-2 infection and contribute to knowledge regarding the course of fatal COVID-19 in children. Furthermore, our findings of ChP infection and viral neurotropism suggest that SARS-CoV-2 may invade the central nervous system by blood-cerebrospinal fluid barrier disruption.</AbstractText>Carlos Chagas Filho Foundation for Supporting Research in the State of Rio de Janeiro (FAPERJ); the National Council for Scientific and Technological Development (CNPq) and Coordination for the Improvement of Higher Education Personnel (CAPES), in addition to intramural grants from D'Or Institute for Research and Education.</AbstractText><AbstractText Label="EDITOR'S NOTE" NlmCategory="UNASSIGNED">This translation in Portuguese was submitted by the authors and we reproduce it as supplied. It has not been peer reviewed. Our editorial processes have only been applied to the original abstract in English, which should serve as reference for this manuscript.</AbstractText>Complicações sistêmicas e neurológicas foram descritas em adultos com COVID-19 grave. Neste trabalho, descrevemos a infecção por SARS-CoV-2, incluindo sua neuroinvasão, nos tecidos post-mortem</i> de uma criança.</AbstractText><AbstractText Label="MÉTODOS" NlmCategory="UNASSIGNED">Realizamos a autópsia completa de uma criança de 14 meses que morreu de pneumonite por COVID-19. Cortes histológicos de múltiplos órgãos foram corados com Hematoxilina e Eosina. A coloração de Luxol Fast Blue para mielina e imuno-histoquímica foram realizadas em áreas selecionadas do cérebro. A presença de SARS-CoV-2 foi investigada por imunomarcação com anticorpo anti-proteína spike e por RT-qPCR.</AbstractText>As lesões incluíram microtrombose, congestão pulmonar, edema intersticial, infiltrados linfocíticos, lesão bronquiolar, colapso dos espaços alveolares, atrofia cortical e perda neuronal grave. A presença de SARS-CoV-2 foi observada ao longo da região apical do epitélio do plexo coróide (PC) e nas células ependimárias do ventrículo lateral, mas ficou restrita aos capilares e vasos do PC em outras regiões. A infecção do tecido cerebral por SARS-CoV-2 foi confirmada por RT-qPCR em fragmentos do PC, ventrículo lateral e cortex cerebral.</AbstractText><AbstractText Label="INTERPRETAÇÃO" NlmCategory="UNASSIGNED">Nossos resultados mostram alterações histopatológicas multissistêmicas causadas pela infecção por SARS-CoV-2 e contribuem para ampliar o conhecimento sobre a evolução da COVID-19 fatal em crianças. Além disso, nossos achados sobre a infecção no PC e neurotropismo viral sugerem que o SARS-CoV-2 pode invadir o sistema nervoso central pela ruptura da barreira sangue-líquido cefalorraquidiano.</AbstractText>Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ) e Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), além de financiamento intramural do Instituto D'Or de Pesquisa e Educação.</AbstractText>© 2021 The Author(s). Published by Elsevier Ltd.</CopyrightInformation> |
2,331,053 | Prenatal onset of the neuroradiologic phenotype of pyruvate carboxylase deficiency due to homozygous <i>PC</i> c.1828G > A mutations. | Pyruvate carboxylase (PC) deficiency (MIM# 266150) is an autosomal recessive disorder with three subtypes. Patients homozygous for the c.1828G > A mutation in the <i>PC</i> gene belong to type A, which typically has infantile onset, severe to profound developmental delay, hypotonia, and lactic acidemia. We report the neuroimaging abnormalities in a 33-week gestation infant homozygous for the c.1828G > A mutation. Brain magnetic resonance imaging on day 10 of life revealed increased T2 signal within the subcortical and periventricular white matter, an immature gyral pattern, large periventricular cysts with mass effect on the lateral ventricles, and dilatation of the occipital and temporal horns. Magnetic resonance spectroscopy showed reduced creatine and NAA peaks, a relatively high choline peak and no lactate peak. These findings were observed prior to the neonate experiencing any episodes of decompensation with lactic acidosis. The presence of these brain anomalies at this gestational age, prior to any metabolic decompensation, supports the essential role of PC in normal brain morphogenesis and the resulting in-utero brain anomalies secondary to its deficiency. Our experience with this affected premature infant and many others we have managed with the same founder mutation suggests that the clinical phenotypes of the type A and the more severe type B PC deficient patients are on a spectrum rather than distinct subtypes. |
2,331,054 | Role of chest CT scan in atypical cardiac trauma management: Left ventricle injury by a nail gun. | We report a case of an accidental penetrating cardiac trauma with a nail gun. A 28-year-old man was repairing a sofa with a nail gun when a nail was misfired to his chest. At the time of his presentation, he underwent chest CT scan, showing the nail as a sharp hyperdense foreign body penetrating the chest wall passing through the lower lobe of the left lung and finally the anterior aspect of left ventricle cavity. This report highlights the utility of the chest CT scan to detect trajectory of the misfired nail accurately and instantaneously in a hemodynamically stable patient to assist in the surgery plan. |
2,331,055 | Clinical outcomes of left bundle branch area pacing compared to right ventricular pacing: Results from the Geisinger-Rush Conduction System Pacing Registry. | Left bundle branch area pacing (LBBAP) has been shown to be a feasible option for patients requiring ventricular pacing.</AbstractText>The purpose of this study was to compare clinical outcomes between LBBAP and RVP among patients undergoing pacemaker implantation METHODS: This observational registry included patients who underwent pacemaker implantations with LBBAP or RVP for bradycardia indications between April 2018 and October 2020. The primary composite outcome included all-cause mortality, heart failure hospitalization (HFH), or upgrade to biventricular pacing. Secondary outcomes included the composite endpoint among patients with a prespecified burden of ventricular pacing and individual outcomes.</AbstractText>A total of 703 patients met inclusion criteria (321 LBBAP and 382 RVP). QRS duration during LBBAP was similar to baseline (121 ± 23 ms vs 117 ± 30 ms; P = .302) and was narrower compared to RVP (121 ± 23 ms vs 156 ± 27 ms; P <.001). The primary composite outcome was significantly lower with LBBAP (10.0%) compared to RVP (23.3%) (hazard ratio [HR] 0.46; 95%T confidence interval [CI] 0.306-0.695; P <.001). Among patients with ventricular pacing burden >20%, LBBAP was associated with significant reduction in the primary outcome compared to RVP (8.4% vs 26.1%; HR 0.32; 95% CI 0.187-0.540; P <.001). LBBAP was also associated with significant reduction in mortality (7.8% vs 15%; HR 0.59; P = .03) and HFH (3.7% vs 10.5%; HR 0.38; P = .004).</AbstractText>LBBAP resulted in improved clinical outcomes compared to RVP. Higher burden of ventricular pacing (>20%) was the primary driver of these outcome differences.</AbstractText>Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.</CopyrightInformation> |
2,331,056 | MA-SOCRATIS: An automatic pipeline for robust segmentation of the left ventricle and scar. | Multi-atlas segmentation of cardiac regions and total infarct scar (MA-SOCRATIS) is an unsupervised automatic pipeline to segment left ventricular myocardium and scar from late gadolinium enhanced MR images (LGE-MRI) of the heart. We implement two different pipelines for myocardial and scar segmentation from short axis LGE-MRI. Myocardial segmentation has two steps; initial segmentation and re-estimation. The initial segmentation step makes a first estimate of myocardium boundaries by using multi-atlas segmentation techniques. The re-estimation step refines the myocardial segmentation by a combination of k-means clustering and a geometric median shape variation technique. An active contour technique determines the unhealthy and healthy myocardial wall. The scar segmentation pipeline is a combination of a Rician-Gaussian mixture model and full width at half maximum (FWHM) thresholding, to determine the intensity pixels in scar regions. Following this step a watershed method with an automatic seed-points framework segments the final scar region. MA-SOCRATIS was evaluated using two different datasets. In both datasets ground truths were based on manual segmentation of short axis images from LGE-MRI scans. The first dataset included 40 patients from the MS-CMRSeg 2019 challenge dataset (STACOM at MICCAI 2019). The second is a collection of 20 patients with scar regions that are challenging to segment. MA-SOCRATIS achieved robust and accurate performance in automatic segmentation of myocardium and scar regions without the need of training or tuning in both cohorts, compared with state-of-the-art techniques (intra-observer and inter observer myocardium segmentation: 81.9% and 70% average Dice value, and scar (intra-observer and inter observer segmentation: 70.5% and 70.5% average Dice value). |
2,331,057 | Translational value of choroid plexus imaging for tracking neuroinflammation in mice and humans. | Neuroinflammation is a pathophysiological hallmark of multiple sclerosis and has a close mechanistic link to neurodegeneration. Although this link is potentially targetable, robust translatable models to reliably quantify and track neuroinflammation in both mice and humans are lacking. The choroid plexus (ChP) plays a pivotal role in regulating the trafficking of immune cells from the brain parenchyma into the cerebrospinal fluid (CSF) and has recently attracted attention as a key structure in the initiation of inflammatory brain responses. In a translational framework, we here address the integrity and multidimensional characteristics of the ChP under inflammatory conditions and question whether ChP volumes could act as an interspecies marker of neuroinflammation that closely interrelates with functional impairment. Therefore, we explore ChP characteristics in neuroinflammation in patients with multiple sclerosis and in two experimental mouse models, cuprizone diet-related demyelination and experimental autoimmune encephalomyelitis. We demonstrate that ChP enlargement-reconstructed from MRI-is highly associated with acute disease activity, both in the studied mouse models and in humans. A close dependency of ChP integrity and molecular signatures of neuroinflammation is shown in the performed transcriptomic analyses. Moreover, pharmacological modulation of the blood-CSF barrier with natalizumab prevents an increase of the ChP volume. ChP enlargement is strongly linked to emerging functional impairment as depicted in the mouse models and in multiple sclerosis patients. Our findings identify ChP characteristics as robust and translatable hallmarks of acute and ongoing neuroinflammatory activity in mice and humans that could serve as a promising interspecies marker for translational and reverse-translational approaches. |
2,331,058 | Circulating ghrelin crosses the blood-cerebrospinal fluid barrier via growth hormone secretagogue receptor dependent and independent mechanisms. | Ghrelin is a peptide hormone mainly secreted from gastrointestinal tract that acts via the growth hormone secretagogue receptor (GHSR), which is highly expressed in the brain. Strikingly, the accessibility of ghrelin to the brain seems to be limited and restricted to few brain areas. Previous studies in mice have shown that ghrelin can access the brain via the blood-cerebrospinal fluid (CSF) barrier, an interface constituted by the choroid plexus and the hypothalamic tanycytes. Here, we performed a variety of in vivo and in vitro studies to test the hypothesis that the transport of ghrelin across the blood-CSF barrier occurs in a GHSR-dependent manner. In vivo, we found that the uptake of systemically administered fluorescent ghrelin in the choroid plexus epithelial (CPE) cells and in hypothalamic tanycytes depends on the presence of GHSR. Also, we detected lower levels of CSF ghrelin after a systemic ghrelin injection in GHSR-deficient mice, as compared to WT mice. In vitro, the internalization of fluorescent ghrelin was reduced in explants of choroid plexus from GHSR-deficient mice, and unaffected in primary cultures of hypothalamic tanycytes derived from GHSR-deficient mice. Finally, we found that the GHSR mRNA is detected in a pool of CPE cells, but is nearly undetectable in hypothalamic tanycytes with current approaches. Thus, our results suggest that circulating ghrelin crosses the blood-CSF barrier mainly by a mechanism that involves the GHSR, and also possibly via a GHSR-independent mechanism. |
2,331,059 | Diagnostic Accuracy of Longitudinal Evaluation of Central Nervous System Sonoelastography in Preterm and Term Neonates. | The objective of this study was to evaluate the brain elasticity of the central nervous system in preterm and term neonates.</AbstractText>Seventy-seven healthy preterm and term neonates (mean gestational age [GA], 37.5 weeks; range, 32.6-40.5 weeks) were included in the study. Periventricular and subcortical white matter, cortical gray matter, and ventricle and subdural spaces were examined with strain elastography ratios. Each patient underwent sonography evaluation twice. The mean age at the time of sonographic evaluation was 9 days (range, 4-15 days) for the first evaluation and 37 days (range, 31-47 days) for the second evaluation. The ratios were correlated with GA, birth weight.</AbstractText>The caudate nucleus and cortical gray matter strain ratios were significantly higher than the periventricular and subcortical white matter strain ratios (P < 0.001). There was a positive relationship between GA and periventricular white matter elastographic scores on the two measurements (P = 0.022 and 0.018, respectively). The term neonates have higher strain rations compared with the preterm neonates at the first assessment (P < 0.01). At the evaluation of the area under the curve for the sonographic examination for the receiver operating characteristic curve, the periventricular white matter was 0.742 (95% confidence interval, 0.689-0.790), and it was 0.773 (95% confidence interval, 0.722-0.818) for the subcortical white matter.</AbstractText>Neonatal brain development, maturation, and myelination can be assessed by strain elastography. These findings should be evaluated with further larger cohorts that could help to prevent neonatal brain damages.</AbstractText>Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.</CopyrightInformation> |
2,331,060 | Automated segmentation of biventricular contours in tissue phase mapping using deep learning. | Tissue phase mapping (TPM) is an MRI technique for quantification of regional biventricular myocardial velocities. Despite its potential, clinical use is limited due to the requisite labor-intensive manual segmentation of cardiac contours for all time frames. The purpose of this study was to develop a deep learning (DL) network for automated segmentation of TPM images, without significant loss in segmentation and myocardial velocity quantification accuracy compared with manual segmentation. We implemented a multi-channel 3D (three dimensional; 2D + time) dense U-Net that trained on magnitude and phase images and combined cross-entropy, Dice, and Hausdorff distance loss terms to improve the segmentation accuracy and suppress unnatural boundaries. The dense U-Net was trained and tested with 150 multi-slice, multi-phase TPM scans (114 scans for training, 36 for testing) from 99 heart transplant patients (44 females, 1-4 scans/patient), where the magnitude and velocity-encoded (V<sub>x</sub> , V<sub>y</sub> , V<sub>z</sub> ) images were used as input and the corresponding manual segmentation masks were used as reference. The accuracy of DL segmentation was evaluated using quantitative metrics (Dice scores, Hausdorff distance) and linear regression and Bland-Altman analyses on the resulting peak radial and longitudinal velocities (V<sub>r</sub> and V<sub>z</sub> ). The mean segmentation time was about 2 h per patient for manual and 1.9 ± 0.3 s for DL. Our network produced good accuracy (median Dice = 0.85 for left ventricle (LV), 0.64 for right ventricle (RV), Hausdorff distance = 3.17 pixels) compared with manual segmentation. Peak V<sub>r</sub> and V<sub>z</sub> measured from manual and DL segmentations were strongly correlated (R ≥ 0.88) and in good agreement with manual analysis (mean difference and limits of agreement for V<sub>z</sub> and V<sub>r</sub> were -0.05 ± 0.98 cm/s and -0.06 ± 1.18 cm/s for LV, and -0.21 ± 2.33 cm/s and 0.46 ± 4.00 cm/s for RV, respectively). The proposed multi-channel 3D dense U-Net was capable of reducing the segmentation time by 3,600-fold, without significant loss in accuracy in tissue velocity measurements. |
2,331,061 | Effect of N‑terminal region of human parvovirus B19‑VP1 unique region on cardiac injury in naïve mice. | A unique region of human parvovirus B19 virus‑VP1 (B19V‑VP1u) has been linked to a variety of cardiac disorders. However, the precise role of B19V‑VP1u in inducing cardiac injury remains unknown. The present study investigated the effects of B19V‑VP1u and different regions of B19V‑VP1u, including B19V‑VP1uA (residues 1‑60), B19V‑VP1uB (residues 61‑129), B19V‑VP1uC (residues 130‑195) and B19V‑VP1uD (residues 196‑227), on inducing cardiac injury in naïve mice by zymography, immunoblotting, H&E staining and cytokine immunoassay. A significantly higher MMP‑9/MMP‑2 ratio and increased levels of inflammatory cytokines, including IL‑6 and IL‑1β, were detected in the left ventricles of the mice injected with B19V‑non‑structural protein 1 (B19V‑NS1) and B19V‑VP1u, accompanied by increased expression levels of phosphorylated (p‑)ERK and p‑P38. Significantly upregulated expression levels of atrial natriuretic peptide (ANP), heart‑type fatty acid‑binding protein (H‑FABP) and creatine kinase isoenzyme‑MB (CK‑MB), which are well‑known cardiac injury markers, as well as increased infiltration of lymphocytes, were detected in the left ventricles of the mice injected with B19V‑VP1, B19V‑NS1 and B19V‑VP1u. Moreover, a significantly higher MMP‑9/MMP‑2 ratio and increased levels of IL‑6 and IL‑1β were observed in the left ventricles of the mice injected with B19V‑VP1u, B19V‑VP1u‑A, B19V‑VP1u‑B and B19V‑VP1u‑C, accompanied by upregulated p‑ERK and p‑P38 expression. Notably, significantly lower levels of IL‑6 and IL‑1β were observed in the left ventricles of the mice injected with B19V‑VP1uD. Furthermore, significantly increased ANP, H‑FABP and CK‑MB expression levels were detected in the left ventricles of the mice injected with B19V‑VP1u, B19V‑VP1u‑A and B19V‑VP1u‑B, along with enhanced infiltration of lymphocytes. Significantly higher serum IL‑1β, IL‑6, TNF‑α and IFN‑γ levels were also detected in the mice injected with B19V‑VP1u, B19V‑VP1u‑A and B19V‑VP1u‑B. To the best of our knowledge, the findings of the present study were the first to demonstrate that the N‑terminal region (residues 1‑129) of B19V‑VP1u induces an increase in the levels of cardiac injury markers, thus providing evidence for understanding the possible functional regions within B19V‑VP1u. |
2,331,062 | A case of an atypical teratoid/rhabdoid tumor with distinctive histology in the pineal region in an adult patient. | A 31-year-old man suffered from headaches and presented at a hospital after the symptom worsened. Obstructive hydrocephalus and a pineal tumor were identified, and he was transferred to our hospital for further investigation and treatment. Cranial computed tomography revealed a hypodense mass lesion on the right of the pineal region, and calcifications and enlargement of the lateral and third cerebral ventricles were also evident. Blood tests were negative for all tumor markers. Laparoscopic biopsy and third-ventricle fenestration were performed that day as an emergency surgery to treat the obstructive hydrocephalus. Postoperative cranial magnetic resonance imaging revealed a solid tumor that was hypointense on T1-weighted imaging, hyperintense on T2-weighted imaging, and heterogeneously enhanced by Gd. Subsequently, the tumor increased in size, and craniotomy and tumorectomy were performed. Histologically, the tumor proliferated as round or short spindle-shaped cells in a myxoid matrix, forming arrays that surrounded the blood vessels. As a few cells with eosinophilic cytoplasm were also present and immunostaining for INI-1 was negative, the patient was diagnosed with atypical teratoid/rhabdoid tumor (AT/RT). AT/RT of the pineal region in adults is rare, and herein, we report the morphological characteristics of this case and reviewed the relevant literature. |
2,331,063 | The role of mesencephalic aqueduct obstruction in hydrocephalus development: a case report. | We report on three patients with mesencephalic aqueduct obstruction, which completely blocked the cerebrospinal fluid communication between the third and fourth cerebral ventricle, demonstrated by standard and high-resolution magnetic resonance sequences. Only one patient developed radiological and clinical presentation of hydrocephalus, without radiological signs of increased intraventricular pressure. The remaining two patients did not show clinical signs of hydrocephalus and had a normal radiological presentation of the ventricular system. These findings contradict the classical concept of cerebrospinal fluid physiology. This concept assumes a unidirectional circulation of cerebrospinal fluid through the mesencephalic aqueduct from the secretion site, predominantly in the choroid plexuses, to the resorption site, predominantly in the dural venous sinuses. Therefore, the obstruction of the mesencephalic aqueduct would inevitably lead to triventricular hypertensive hydrocephalus in all patients. The current observations, however, accord with the new concept of cerebrospinal fluid physiology, which postulates that cerebrospinal fluid does not circulate unidirectionally because it is both formed and resorbed along the entire capillary network within the central nervous system. |
2,331,064 | Microscopic biopsy after unsuccessful endoscopic biopsy for primary central nervous system lymphoma of the corpus callosum: A case report. | Primary central nervous system lymphoma (PCNSL) is a rare tumor with a poor prognosis. Early brain biopsy is essential to avoid a diagnostic delay. To date, reports of successful diagnosis for PCNSL of the corpus callosum by endoscopic biopsy are rare.</AbstractText>Herein, we report the case of an elderly woman with PCNSL of the corpus callosum who initially presented with rapidly progressive dementia. The condition was finally diagnosed by microscopic biopsy after unsuccessful endoscopic biopsy. Moreover, the postoperative course was uneventful. She is currently receiving systemic chemotherapy.</AbstractText>Early diagnosis and subsequent systemic chemotherapy with or without whole brain radiotherapy are critical for PCNSL. Endoscopic biopsy may be a diagnostic option for suspected PCNSL, although stereotactic needle biopsy is most commonly used.</AbstractText>Utilizing neuronavigation and 5-aminolevulinic acid (ALA) fluorescence guidance could be helpful in identifying lesions insufficiently exposed by endoscopic visualization. However, cerebrospinal fluid (CSF) loss due to the endoscopic approach through the ventricle might be a cause of neuronavigation misregistration.</AbstractText>© 2021 The Authors.</CopyrightInformation> |
2,331,065 | Incidental Presentation of Dandy Walker Variant in 66 Year Male Patient. | Dandy-Walker variant consists of vermian hypoplasia and cystic dilatation of the fourth ventricle, without enlargement of the posterior fossa is a distinctive entity believed to represent a mild subtype of Dandy-Walker complex. We report a case of 66 year male presented with right sided hemiparesis due to ischemic stroke whose imaging showed incidental findings Dandy walker variant. This Incidental Dandy Walker malformation finding in adult is rare with only a few cases reported till date. |
2,331,066 | An Updated Review of the Efficacy and Safety of Direct Oral Anticoagulants in Treatment of Left Ventricular Thrombus. | Left ventricular (LV) thrombus is a potentially serious complication affecting males and females with ischemic and nonischemic cardiomyopathy-specifically, after acute myocardial infarctions of the anterior left ventricular wall and long-standing tachyarrhythmias, respectively. LV thrombi pose significant risks for systemic embolization and devastating stroke events, while also demanding a treatment carrying inherent risks of its own. It is therefore imperative to have accurate detection of these ventricular thrombi and an appropriate understanding of the risks and benefits regarding management. Anticoagulation using warfarin has long been established as the gold-standard level of care in the current guidelines of the American College of Cardiology but the advent of direct oral anticoagulants (DOACs) prompts a re-examination of the literature. The particular question we seek to answer lies in the efficacy of these drugs and the safety and outcomes when used to treat LV thrombi. Recent case reports, meta-analyses, and most recently, the breakthrough of 2 novel randomized controlled trials have shown DOACs to be a promising treatment for LV thrombus. Contrarily, some retrospective cohort reviews suggest less-than-promising outcomes. This meta-analysis hopes to provide a current, curated review of up-to-date safety and efficacy in the documented tales of DOACs and LV thrombi that has been published since early 2020-by selecting these curated case studies, and analyzing the most recent randomized controlled trials, we hope to engage the reader with clearer illustrations of the key components of both the advocacy and warning of this pharmaceutical intervention. |
2,331,067 | IL-17 triggers the onset of cognitive and synaptic deficits in early stages of Alzheimer's disease. | Neuroinflammation in patients with Alzheimer's disease (AD) and related mouse models has been recognized for decades, but the contribution of the recently described meningeal immune population to AD pathogenesis remains to be addressed. Here, using the 3xTg-AD model, we report an accumulation of interleukin-17 (IL-17)-producing cells, mostly γδ T cells, in the brain and the meninges of female, but not male, mice, concomitant with the onset of cognitive decline. Critically, IL-17 neutralization into the ventricles is sufficient to prevent short-term memory and synaptic plasticity deficits at early stages of disease. These effects precede blood-brain barrier disruption and amyloid-beta or tau pathology, implying an early involvement of IL-17 in AD pathology. When IL-17 is neutralized at later stages of disease, the onset of short-memory deficits and amyloidosis-related splenomegaly is delayed. Altogether, our data support the idea that cognition relies on a finely regulated balance of "inflammatory" cytokines derived from the meningeal immune system. |
2,331,068 | Accurate placement of parieto-occipital shunt ventricular catheter: use of craniometrics and technical note. | Ventriculoperitoneal shunt insertion is one of the most commonly performed procedures in neurosurgery but has a relatively high complication rate. One important source of complications is shunt malposition from erroneous placement of the parieto-occipital burr hole or poor shunt trajectory. There are significant variations in the freehand parieto-occipital approach amongst neurosurgeons that are derived from variations in technique or experience. The patient's skull shape or size is also often not taken into consideration if fixed measurements are used to define the burr hole entry point. The authors suggest a variation to the technique of ventricular catheter placement by relying on the patient's own craniometrics and skull landmarks.</AbstractText>The technique is illustrated and supported by analysis of a case series of 25 patients undergoing shunt placement.</AbstractText>By this method, all shunts were positioned in the lateral ventricle. Using a 3-point scale, the catheter position was evaluated: grade 1, free floating in cerebrospinal fluid; grade 2, touching the choroid plexus or ventricular wall; and grade 3, tip within the parenchyma. The catheter position was grade 1 in sixteen (64%) cases and grade 2 in nine (36%) cases; none was grade 3. Only one shunt malfunction occurred from proximal shunt obstruction in the series.</AbstractText>The use of this technique aims to reduce operator and patient variability as contributors to shunt malposition, to increase user reproducibility and decrease the learning curve for trainees. Further prospective study could be designed to validate the technique.</AbstractText>© 2021. Crown.</CopyrightInformation> |
2,331,069 | Residual Learning: A New Paradigm to Improve Deep Learning-Based Segmentation of the Left Ventricle in Magnetic Resonance Imaging Cardiac Images. | Recently, magnetic resonance imaging (MRI) has become a useful tool for the early detection of heart failure. A vital step of this process is a valid measurement of the left ventricle's properties, which seriously depends on the accurate segmentation of the heart in captured images. Although various schemes have been tested for this segmentation so far, the latest proposed methods have used the concept of deep learning to estimate the range of the left ventricle in cardiac MRI images. While deep learning methods can lead to better results than their classical alternatives, but unfortunately, the gradient vanishing and exploding problems may hamper their efficiency for the accurate segmentation of the left ventricle in MRI heart images.</AbstractText>In this article, a new concept called residual learning is utilized to improve the performance of deep learning schemes against gradient vanishing problems. For this purpose, the Residual Network of Residual Network (i.e., Residual of Residual) substructure is utilized inside the main deep learning architecture (e.g., Unet), which provides more significant detection indexes.</AbstractText>The proposed method's performances and its alternatives were evaluated on Sunnybrook Cardiac Data as a reliable dataset in the left ventricle segmentation. The results show that the detection parameters are improved at least by 5%, 3.5%, 8.1%, and 11.4% compared to its deep alternatives in terms of Jaccard, Dice, precision, and false-positive rate indexes, respectively. These improvements were made when the recall parameter was reduced to a negligible value (i.e., approximately 1%). Overall, the proposed method can be used as a suitable tool for more accurate detection of the left ventricle in MRI images.</AbstractText>Copyright: © 2021 Journal of Medical Signals & Sensors.</CopyrightInformation> |
2,331,070 | Use of FVB Myc-CaP cells as an immune competent, androgen receptor positive, mouse model of prostate cancer bone metastasis. | Prostate cancer (PCa) metastasis research has been hamstrung by lack of animal models that closely resemble the disease present in most patients - that metastasize to bone, are dependent on the androgen receptor (AR), and grow in an immune competent host. Here, we adapt the Myc-CaP cell line for use as a PCa androgen dependent, immune competent bone metastases model and characterize the metastases. After injection into the left cardiac ventricle of syngeneic FVB/NJ mice, these cells formed bone metastases in the majority of animals; easily visible on H&E sections and confirmed by immunohistochemistry for Ar and epithelial cell adhesion molecule. Mediastinal tumors were also observed. We also labeled Myc-CaP cells with tdTomato, and confirmed the presence of cancer cells in bone by flow cytometry. To adapt the model to a bone predominant metastasis pattern and further examine the bone phenotype, we labeled the cells with luciferase, injected in the tibia and observed tumor formation only in tibia with a mixed osteolytic/osteoblastic phenotype. The presence of Myc-CaP tumors significantly increased tibia bone volume as compared to sham injected controls. The osteoclast marker, TRAcP-5b was not significantly changed in plasma from tibial tumor bearing animals vs. sham animals. However, conditioned media from Myc-CaP cells stimulated osteoclast formation <i>in vitro</i> from FVB/NJ mouse bone marrow. Overall, Myc-CaP cells injected in the left ventricle or tibia of syngeneic mice recapitulate key aspects of human metastatic PCa. |
2,331,071 | Vector Flow Mapping Application in Local Cardiac Function in Hypertension Assessment. | This study aims to investigate the clinical significance of vector flow mapping (VFM) by observing and quantifying energy loss (EL) during different phases and in different left ventricle (LV) segments.</AbstractText>42 healthy physical examination subjects and 89 patients with hypertension (HTN) were enrolled in the present study. The patients with HTN were divided into two groups: the left ventricular hypertrophy group (LVH) (n = 51) and the non-left ventricular hypertrophy group (NLVH) (n = 38), while the healthy patients were control group. VFM analysis software DSA-RS1 was used to calculate EL during the rapid filling phase (P1), slow filling phase (P2), atrial contraction phase (P3), and rapid ejection phase (P4). The energy loss of basal segment (EL-B), middle segment (EL-M) and apical segment (EL-A) of left ventricle in different phases was calculated and compared among the three groups.</AbstractText>In controls, segmental EL showed a gradual increase from the apex to the base during diastole; however, the regularity was not found in the HTN patients. During both P1 and P2 EL-B, EL-M and EL-A were significantly higher in the NLVH group and the LVH group compared with the control group (P</i> < 0.05). EL in LVH group was the highest among the three groups (P</i> < 0.05). During P3, EL-B, EL-M and EL-A were increased in the NLVH group and LVH group compared with the control group. However, EL-M and EL-A in LVH group were significantly lower than the NLVH group (P</i> < 0.05). During P4, EL of all segments was significantly higher in the NLVH group and LVH group compared with the control group (P</i> < 0.05).</AbstractText>VFM can visually quantify hydrodynamic LV changes in healthy subjects. The EL levels in the different LV segments during different phases were significantly higher in the patients with HTN compared with the healthy subjects.</AbstractText>© 2021 Zuo et al.</CopyrightInformation> |
2,331,072 | A single low-energy shockwave pulse opens blood-cerebrospinal fluid barriers and facilitates gastrodin delivery to alleviate epilepsy. | The blood-cerebrospinal fluid barrier (BCSFB) is another gatekeeper between systemic circulation and the central nervous system (CNS), mainly present at the boundary between choroid plexuses and the ventricular system. This study demonstrates BCSFB opening in rats by single pulse of low-energy focused shockwave (FSW, energy flux density 0.03 mJ/mm<sup>2</sup>, 2 × 10<sup>6</sup> microbubbles/kg) treatment at lateral ventricle, resulting in significantly elevated cerebrospinal fluid (CSF) concentrations of systemically-administered gastrodin (GTD) (4 times vs. control within 3 hrs) that remained detectable for 24 hrs. The FSW-GTD group had significantly lower Racine's scale (<4) and zero mortality (n = 30) after lithium-pilocarpine-induced epilepsy. Electrophysiological recordings showed decreased epileptiform discharges, and brain section histology revealed reduced inflammation, oxidative stress and apoptosis, when compared with groups without FSW (Racine's scale: 4 ∼ 5; mortality: 26.67 ∼ 36.67%). FSW-mediated BCSFB opening provides a promising alternative for controlled-delivery of therapeutics into the CNS, offering rapid and widespread medication distribution. The technique could by applied in the development of novel therapies for various CNS diseases. |
2,331,073 | Selective extension of cerebral vascular calcification in an autopsy case of Fahr's syndrome associated with asymptomatic hypoparathyroidism. | We report an autopsy case of Fahr's syndrome in an 85-year-old woman associated with asymptomatic hypoparathyroidism. The patient was diagnosed as having brain calcification at 65 years of age. She developed mild dementia at 75, parkinsonism at 76, and severe dementia at 82. Computed tomography revealed extensive, symmetric intracranial calcification, involving both sides of the basal ganglia and cerebellar dentate nuclei, and severe cerebral atrophy that developed afterwards. A neuropathological examination revealed intracranial calcification, particularly in the wall of the arterioles and capillaries having numerous calcium deposits. Severe vascular calcification and severe neuronal loss without α-synuclein accumulation were found in the substantia nigra. There were high-level neuropathological changes indicative of Alzheimer's disease. Although the colocalization of calcium and amyloid-β deposits in the same arterial wall was rare, both of them were located in a similar layer of the arterial wall. The vascular calcification in the basal ganglia spread continuously through the corona radiata into the selective cerebral areas along the medullary arteries, but did not involve the corpus callosum or insular region. Stone formation was observed at the corona radiata adjacent to the superolateral angles of the lateral ventricles. We hypothesized that there would be a stereotypical extension pattern of vascular calcification related to the arrangement of penetrating arteries in Fahr's syndrome. |
2,331,074 | A malignant choroid plexus tumour with prevailing immature blastematous elements.<Pagination><StartPage>e12764</StartPage><MedlinePgn>e12764</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">e12764</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1111/nan.12764</ELocationID><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Tauziède-Espariat</LastName><ForeName>Arnault</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Neuropathology, GHU Paris-Neurosciences, Sainte-Anne Hospital, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pagès</LastName><ForeName>Mélanie</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Neuropathology, GHU Paris-Neurosciences, Sainte-Anne Hospital, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institut Curie, Paris Sciences Lettres University, SIREDO, INSERM U830, Laboratory of Translational Research in Paediatric Oncology, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Masliah-Planchon</LastName><ForeName>Julien</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Genetic, Curie Institute, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bourdeaut</LastName><ForeName>Franck</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Institut Curie, SIREDO (Care, Innovation, Research in Pediatric, Adolescent and Young Adults Oncology), Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Doz</LastName><ForeName>François</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Institut Curie, SIREDO (Care, Innovation, Research in Pediatric, Adolescent and Young Adults Oncology), Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université de Paris, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Beccaria</LastName><ForeName>Kévin</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Paediatric Neurosurgery, Necker Hospital, APHP, Université Paris Descartes, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Boddaert</LastName><ForeName>Nathalie</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Radiology, Necker Hospital, APHP, Université Paris Descartes, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hasty</LastName><ForeName>Lauren</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Neuropathology, GHU Paris-Neurosciences, Sainte-Anne Hospital, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lechapt</LastName><ForeName>Emmanuèle</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Department of Neuropathology, GHU Paris-Neurosciences, Sainte-Anne Hospital, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Thomas</LastName><ForeName>Christian</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Institute of Neuropathology, University Hospital Münster, Münster, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Paulus</LastName><ForeName>Werner</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Institute of Neuropathology, University Hospital Münster, Münster, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Varlet</LastName><ForeName>Pascale</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Neuropathology, GHU Paris-Neurosciences, Sainte-Anne Hospital, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hasselblatt</LastName><ForeName>Martin</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institute of Neuropathology, University Hospital Münster, Münster, Germany.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>09</Month><Day>15</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Neuropathol Appl Neurobiol</MedlineTA><NlmUniqueID>7609829</NlmUniqueID><ISSNLinking>0305-1846</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D002675" MajorTopicYN="N">Child, Preschool</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002831" MajorTopicYN="N">Choroid Plexus</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016545" MajorTopicYN="N">Choroid Plexus Neoplasms</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019175" MajorTopicYN="N">DNA Methylation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009447" MajorTopicYN="N">Neuroblastoma</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">DNA methylation profiling</Keyword><Keyword MajorTopicYN="N">blastematous</Keyword><Keyword MajorTopicYN="N">choroid plexus tumour</Keyword><Keyword MajorTopicYN="N">mesenchymal</Keyword></KeywordList><CoiStatement>The authors declare that they have no conflict of interest directly related to the topic of this article.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="revised"><Year>2021</Year><Month>8</Month><Day>11</Day></PubMedPubDate><PubMedPubDate PubStatus="received"><Year>2021</Year><Month>3</Month><Day>8</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2021</Year><Month>8</Month><Day>15</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>8</Month><Day>31</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2022</Year><Month>4</Month><Day>1</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>8</Month><Day>30</Day><Hour>12</Hour><Minute>34</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">34460114</ArticleId><ArticleId IdType="pmc">PMC9292497</ArticleId><ArticleId 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Pediatr Blood Cancer. 2007;49(3):266‐273.</Citation><ArticleIdList><ArticleId IdType="pubmed">16807914</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM" IndexingMethod="Automated"><PMID Version="1">34459803</PMID><DateCompleted><Year>2021</Year><Month>10</Month><Day>15</Day></DateCompleted><DateRevised><Year>2021</Year><Month>10</Month><Day>15</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">1940-087X</ISSN><JournalIssue CitedMedium="Internet"><Issue>174</Issue><PubDate><Year>2021</Year><Month>Aug</Month><Day>16</Day></PubDate></JournalIssue><Title>Journal of visualized experiments : JoVE</Title><ISOAbbreviation>J Vis Exp</ISOAbbreviation></Journal>Use of a Percutaneous Ventricular Assist Device/Left Atrium to Femoral Artery Bypass System for Cardiogenic Shock. | The left atrial to femoral artery bypass (LAFAB) system is a mechanical circulatory support (MCS) device used in cardiogenic shock (CS) that bypasses the left ventricle by draining blood from the left atrium (LA) and returning it to the systemic arterial circulation via the femoral artery. It can provide flows ranging from 2.5-5 L/min depending on the size of the cannula. Here, we discuss the mechanism of action of LAFAB, available clinical data, indications for its use in cardiogenic shock, steps of implantation, post-procedural care, and complications associated with the use of this device and their management. We also provide a brief video of the procedural component of device therapy, including the pre-placement preparation, percutaneous placement of the device via transseptal puncture under echocardiographic guidance and the post-operative management of device parameters. |
2,331,075 | Saskatoon berry supplementation prevents cardiac remodeling without improving renal disease in an animal model of reno-cardiac syndrome. | Saskatoon berry (SKB) may have the potential to counter reno-cardiac syndrome owing to its antioxidant capacity. Here, we investigated the renal and cardiovascular effects of SKB-enriched diet in a rat model of reno-cardiac disease. Two groups of wild-type rats (+/+) and two groups of Hannover Sprague-Dawley (Han:SPRD-Cy/+) rats were given either regular diet or SKB diet (10% w/w total diet) for 8 weeks. Body weight, kidney weight, kidney water content, and left ventricle (LV) weight were measured. Blood pressure (BP) was measured by the tail-cuff method. Echocardiography was performed to assess cardiac structure and function. Serum creatinine and malondialdehyde (MDA) were also measured. Han:SPRD-Cy/+ rats had significantly higher kidney weight, kidney water content, LV weight, BP, and creatinine compared with wild-type rats (+/+). The SKB diet supplementation did not reduce kidney weight, kidney water content, BP, and LV weight in Han:SPRD-Cy/+ rats. The SKB diet also resulted in higher systolic BP in Han:SPRD-Cy/+rats. Han:SPRD-Cy/+rats showed cardiac structural remodeling (higher LV wall thickness) without any cardiac functional abnormalities. Han:SPRD-Cy/+ rats also had significantly higher creatinine whereas the concentration of MDA was not different. The SKB diet supplementation reduced cardiac remodeling and the concentration of MDA without altering the concentration of creatinine in Han:SPRD-Cy/+ rats. In conclusion, Han:SPRD-Cy/+ rats developed significant renal disease, high BP, and cardiac remodeling by 8 weeks without cardiac functional impairment. The SKB diet may be useful in preventing cardiac remodeling and oxidative stress in Han:SPRD-Cy/+rats. PRACTICAL APPLICATIONS: Saskatoon berry (SKB) is widely consumed as fresh fruit or processed fruit items and has significant commercial value. It may offer health benefits due to the presence of bioactives such as anthocyanins. SKB has very good culinary flavors, and it is an economically viable fruit crop in many parts of the world. The disease-modifying benefits of SKB are mainly ascribed to the antioxidant nature of its bioactive content. Polycystic kidney disease is a serious condition that can lead to renal and cardiac abnormalities. Here, we showed that SKB supplementation was able to mitigate cardiac remodeling and lower the level of a marker of oxidative stress in an animal model of reno-cardiac syndrome. Our study suggests that SKB possesses beneficial cardioprotective properties. Further evidence from human studies may help in increasing the consumption of SKB as a functional food. |
2,331,076 | Brain Volumetric Alterations in Preclinical HIV-Associated Neurocognitive Disorder Using Automatic Brain Quantification and Segmentation Tool. | This study aimed to determine if people living with HIV (PLWH) in preclinical human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND), with no clinical symptoms and without decreased daily functioning, suffer from brain volumetric alterations and its patterns.</AbstractText>Fifty-nine male PLWH at the HAND preclinical stage were evaluated, including 19 subjects with asymptomatic neurocognitive impairment (ANI), 17 subjects with cognitive abnormality that does not reach ANI (Not reach ANI), and 23 subjects with cognitive integrity. Moreover, 23 healthy volunteers were set as the seronegative normal controls (NCs). These individuals underwent sagittal three-dimensional T1</sub>-weighted imaging (3D T1</sub>WI). Quantified data and volumetric measures of brain structures were automatically segmented and extracted using AccuBrain®</sup>. In addition, the multiple linear regression analysis was performed to analyze the relationship of volumes of brain structures and clinical variables in preclinical HAND, and the correlations of the brain volume parameters with different cognitive function states were assessed by Pearson's correlation analysis.</AbstractText>The significant difference was shown in the relative volumes of the ventricular system, bilateral lateral ventricle, thalamus, caudate, and left parietal lobe gray matter between the preclinical HAND and NCs. Furthermore, the relative volumes of the bilateral thalamus in preclinical HAND were negatively correlated with attention/working memory (left: r</i> = -0.271, p</i> = 0.042; right: r</i> = -0.273, p</i> = 0.040). Higher age was associated with increased relative volumes of the bilateral lateral ventricle and ventricular system and reduced relative volumes of the left thalamus and parietal lobe gray matter. The lower CD4+</sup>/CD8+</sup> ratio was associated with increased relative volumes of the left lateral ventricle and ventricular system. Longer disease course was associated with increased relative volumes of the bilateral thalamus. No significant difference was found among preclinical HAND subgroups in all indices, and the difference between the individual groups (Not reach ANI and Cognitive integrity groups) and NCs was also insignificant. However, there was a significant difference between ANI and NCs in the relative volumes of the bilateral caudate and lateral ventricle.</AbstractText>Male PLWH at the HAND preclinical stage suffer from brain volumetric alterations. AccuBrain®</sup> provides potential value in evaluating HIV-related neurocognitive dysfunction.</AbstractText>Copyright © 2021 Li, Qi, Shi, Wang, Zhang, Luo, Kung, Jiao, Liu, Li and Zhang.</CopyrightInformation> |
2,331,077 | Papillary fibroelastoma in the left ventricle. | We present a 61-year-old woman with a recent transient ischemic attack who presented with presyncope and was ultimately found to have a papillary fibroelastoma at the apex of her left ventricle. She underwent minimally invasive excision of the tumor. |
2,331,078 | Small Nucleus Accumbens and Large Cerebral Ventricles in Infants and Toddlers Prior to Receiving Diagnoses of Autism Spectrum Disorder. | Early interventions for autism spectrum disorder (ASD) are increasingly available, while only 42-50% of ASD children are diagnosed before 3 years old (YO). To identify neuroimaging biomarkers for early ASD diagnosis, we evaluated surface- and voxel-based brain morphometry in participants under 3YO who were later diagnosed with ASD. Magnetic resonance imaging data were retrospectively obtained from patients later diagnosed with ASD at Boston Children's Hospital. The ASD participants with comorbidities such as congenital disorder, epilepsy, and global developmental delay/intellectual disability were excluded from statistical analyses. Eighty-five structural brain magnetic resonance imaging images were collected from 81 participants under 3YO and compared with 45 images from 45 gender- and age-matched nonautistic controls (non-ASD). Using an Infant FreeSurfer pipeline, 236 regionally distributed measurements were extracted from each scan. By t-tests and linear mixed models, the smaller nucleus accumbens and larger bilateral lateral, third, and fourth ventricles were identified in the ASD group. Vertex-wise t-statistical maps showed decreased thickness in the caudal anterior cingulate cortex and increased thickness in the right medial orbitofrontal cortex in ASD. The smaller bilateral accumbens nuclei and larger cerebral ventricles were independent of age, gender, or gestational age at birth, suggesting that there are MRI-based biomarkers in prospective ASD patients before they receive the diagnosis and that the volume of the nucleus accumbens and cerebral ventricles can be key MRI-based early biomarkers to predict the emergence of ASD. |
2,331,079 | Nesfatin-1-like peptide is a negative regulator of cardiovascular functions in zebrafish and goldfish. | Nucleobindins (NUCB1 and NUCB2) were originally identified as calcium and DNA binding proteins. Nesfatin-1 (NEFA/nucleobindin-2-Encoded Satiety and Fat-Influencing proteiN-1) is an 82 amino acid anorexigenic peptide encoded in the N-terminal region of NUCB2. We have shown that nesfatin-1 is a cardiosuppressor in zebrafish. Both NUCB1 and NUCB2 possess a -very highly conserved bioactive core. It was found that a nesfatin-1-like peptide (NLP) encoded in NUCB1 suppresses food intake in fish. In this research, we investigated whether NLP has nesfatin-1-like effects on cardiovascular functions. NUCB1/NLP-like immunoreactivity was found in the atrium and ventricle of the heart and skeletal muscle of zebrafish. Intraperitoneal injection (IP) of either zebrafish NLP or rat NLP suppressed cardiac functions in both zebrafish and goldfish. Irisin and RyR1b mRNA expression was downregulated by NLP in zebrafish cardiac and skeletal muscles. However, cardiac ATP2a2 mRNA expression was elevated after NLP injection. Administration of scrambled NLP did not affect irisin, RyR1b or ATP2a2 mRNA expression in zebrafish. Together, these results implicate NLP as a suppressor of cardiovascular physiology in zebrafish and goldfish. |
2,331,080 | [Relevance of right ventricle in the clinical management of pulmonary arterial hypertension]. | Pulmonary arterial hypertension (PAH) requires structured processes of diagnosis and risk stratification, being the function of the right ventricle (RV) a hallmark prognosis determinant. The main therapeutic goals in PAH are to improve and try to revert RV dysfunction and maintaining a low risk. Currently, there are multiple treatments with different mechanisms of action, the combination of which in double or triple therapy has shown improved results compared to monotherapy. Recent clinical evidence shows the importance of early incorporation of parenteral prostanoids to the scheme, improving RV function and survival. In this review, we discuss the role of the RV function in the diagnosis, prognosis, and follow-up of PAH. We recommend the systematic and standardised evaluation of the RV as well as the early initiation of combined treatment in cases of intermediatehigh risk to try to reach and keep the patient with PAH at a low risk and / or avoid the progression of PAH.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Conde</LastName><ForeName>Rafael E</ForeName><Initials>RE</Initials><AffiliationInfo><Affiliation>Fundación Neumológica Colombiana, Fundación Cardioinfantil, Bogotá, Colombia. E-mail: rconde@neumologica.org.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Diez</LastName><ForeName>Mirta</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Instituto Cardiovascular de Buenos Aires, Buenos Aires, Argentina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dueñas</LastName><ForeName>Rubén</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Clinica Shaio, Bogotá, Colombia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Giacomi</LastName><ForeName>Guillermo</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Servicio de Cardiología Clínica e Invasiva, Hospital Interzonal de Agudos Oscar Alende, Unidad de IC avanzada e HTP, Mar del Plata, Provincia de Buenos Aires, Argentina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lema</LastName><ForeName>Luis</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Departamento de Hipertensión Pulmonar, Instituto Modelo de Cardiología Privado SRL, Córdoba, Argentina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lescano</LastName><ForeName>Adrián</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Departamento de Cardiología, Sanatorio Trinidad Quilmes, Servicio de Cardiología, Grupo BASA Salud, Provincia de Buenos Aires, Argentina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Perna</LastName><ForeName>Eduardo R</ForeName><Initials>ER</Initials><AffiliationInfo><Affiliation>División de Insuficiencia Cardíaca e Hipertensión Pulmonar, Instituto de Cardiología J. F. Cabral, Corrientes, Argentina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zayas Hernández</LastName><ForeName>Nayeli</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Departamento de Cardioneumología, Instituto Nacional de Cardiología Ignacio Chávez, México.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Perrone</LastName><ForeName>Sergio V</ForeName><Initials>SV</Initials><AffiliationInfo><Affiliation>Hospital de Alta Complejidad en Red EL Cruce - Néstor Kirchner, Instituto FLENI e Instituto Argentino de Diagnóstico y Tratamiento, Buenos Aires, Argentina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><CollectiveName>Grupo de Expertos Latinoamericanos en Hipertensión Arterial Pulmonar</CollectiveName></Author></AuthorList><Language>spa</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList><VernacularTitle>Manejo clínico de la hipertensión arterial pulmonar. Relevancia del ventrículo derecho.</VernacularTitle></Article><MedlineJournalInfo><Country>Argentina</Country><MedlineTA>Medicina (B Aires)</MedlineTA><NlmUniqueID>0204271</NlmUniqueID><ISSNLinking>0025-7680</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D006352" MajorTopicYN="N">Heart Ventricles</DescriptorName><QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006976" MajorTopicYN="Y">Hypertension, Pulmonary</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000081029" MajorTopicYN="Y">Pulmonary Arterial Hypertension</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018497" MajorTopicYN="Y">Ventricular Dysfunction, Right</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016278" MajorTopicYN="N">Ventricular Function, Right</DescriptorName></MeshHeading></MeshHeadingList><OtherAbstract Type="Publisher" Language="spa">La hipertensión arterial pulmonar (HAP) requiere procesos estructurados de diagnóstico y estratificación de riesgo, siendo la función del ventrículo derecho (VD) un marcador pronóstico central. Los principales objetivos terapéuticos en la HAP son mejorar y/o intentar revertir la disfunción del VD y mantener condición de bajo riesgo. Actualmente existen múltiples fármacos con diferentes mecanismos de acción cuya combinación en doble o triple terapia ha mostrado mejores resultados que la monoterapia. Evidencia actual demuestra la importancia de incorporar tempranamente prostanoides parenterales al esquema, mejorando la funcionalidad del VD y la supervivencia. En esta revisión se refleja el papel de la función del VD en el diagnóstico, pronóstico y seguimiento de la HAP. Se recomienda la evaluación sistemática y estandarizada del VD, así como el inicio temprano de tratamiento combinado en riesgo intermedio-alto para obtener las metas de alcanzar y mantener un riesgo bajo y/o evitar la progresión de la HAP. |
2,331,081 | Comparison of the function and structural integrity of cryopreserved pulmonary homografts versus decellularized pulmonary homografts after 180 days implantation in the juvenile ovine model.<Pagination><StartPage>347</StartPage><EndPage>366</EndPage><MedlinePgn>347-366</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1007/s10561-021-09948-2</ELocationID><Abstract><AbstractText>Homograft availability and durability remain big challenges. Increasing the post-mortem ischaemic harvesting time beyond 24 h increases the potential donor pool. Cryopreservation, routinely used to preserve homografts, damages the extracellular matrix (ECM), contributing to valve degeneration. Decellularization might preserve the ECM, promoting host-cell infiltration and contributing towards better clinical outcomes. This study compared the performance of cryopreserved versus decellularized pulmonary homografts in the right ventricle outflow tract (RVOT) of a juvenile ovine model. Homografts (n = 10) were harvested from juvenile sheep, subjected to 48 h post-mortem cold ischaemia, cryopreserved or decellularized and implanted in the RVOT of juvenile sheep for 180 days. Valve performance was monitored echocardiographically. Explanted leaflet and wall tissue evaluated histologically, on electron microscopical appearance, mechanical properties and calcium content. In both groups the annulus diameter increased. Cryopreserved homografts developed significant (¾) pulmonary regurgitation, with trivial regurgitation (¼) in the decellularized group. Macroscopically, explanted cryopreserved valve leaflets retracted and thickened while decellularized leaflets remained thin and pliable with good coaptation. Cryopreserved leaflets and walls demonstrated loss of interstitial cells with collapsed collagen, and decellularized scaffolds extensive, uniform ingrowth of host-cells with an intact collagen network. Calcific deposits were shown only in leaflets and walls of cryopreserved explants. Young fibroblasts, with vacuoles and rough endoplasmic reticulum in the cytoplasm, repopulated the leaflets and walls of decellularized scaffolds. Young's modulus of wall tissue in both groups increased significantly. Cryopreserved valves deteriorate over time due to loss of cellularity and calcification, while decellularized scaffolds demonstrated host-cell repopulation, structural maintenance, tissue remodelling and growth potential.</AbstractText><CopyrightInformation>© 2021. The Author(s), under exclusive licence to Springer Nature B.V.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>van den Heever</LastName><ForeName>Johannes Jacobus</ForeName><Initials>JJ</Initials><Identifier Source="ORCID">0000-0001-6905-1779</Identifier><AffiliationInfo><Affiliation>Department of Cardiothoracic Surgery, Faculty of Health Sciences, Internal Box G32), University of the Free State (UFS), P.O. Box 339, Bloemfontein, 9300, South Africa. vdheeverjj@ufs.ac.za.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jordaan</LastName><ForeName>Christiaan Johannes</ForeName><Initials>CJ</Initials><AffiliationInfo><Affiliation>Department of Cardiothoracic Surgery, Faculty of Health Sciences, Internal Box G32), University of the Free State (UFS), P.O. Box 339, Bloemfontein, 9300, South Africa.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lewies</LastName><ForeName>Angelique</ForeName><Initials>A</Initials><Identifier Source="ORCID">0000-0002-5624-1386</Identifier><AffiliationInfo><Affiliation>Department of Cardiothoracic Surgery, Faculty of Health Sciences, Internal Box G32), University of the Free State (UFS), P.O. Box 339, Bloemfontein, 9300, South Africa.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bester</LastName><ForeName>Dreyer</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Cardiothoracic Surgery, Faculty of Health Sciences, Internal Box G32), University of the Free State (UFS), P.O. Box 339, Bloemfontein, 9300, South Africa.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Goedhals</LastName><ForeName>Jacqueline</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Anatomical Pathology, Faculty of Health Sciences, University of the Free State (UFS), P.O. Box 339, Bloemfontein, 9300, South Africa.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Botes</LastName><ForeName>Lezelle</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Health Sciences, Central University of Technology, Free State (CUT), Private Bag X20539, Bloemfontein, 9300, South Africa.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dohmen</LastName><ForeName>Pascal Maria</ForeName><Initials>PM</Initials><AffiliationInfo><Affiliation>Department of Cardiothoracic Surgery, Faculty of Health Sciences, Internal Box G32), University of the Free State (UFS), P.O. Box 339, Bloemfontein, 9300, South Africa.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Klinik und Poliklinik für Herzchirurgie, Klinikdirektor (K), Universitätsmedizin Rostock, Schillingallee 35, 18057, Rostock, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Smit</LastName><ForeName>Francis Edwin</ForeName><Initials>FE</Initials><AffiliationInfo><Affiliation>Department of Cardiothoracic Surgery, Faculty of Health Sciences, Internal Box G32), University of the Free State (UFS), P.O. Box 339, Bloemfontein, 9300, South Africa.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D003160">Comparative Study</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>08</Month><Day>28</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Cell Tissue Bank</MedlineTA><NlmUniqueID>100965121</NlmUniqueID><ISSNLinking>1389-9333</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>9007-34-5</RegistryNumber><NameOfSubstance UI="D003094">Collagen</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D064591" MajorTopicYN="N">Allografts</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003094" MajorTopicYN="N">Collagen</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015925" MajorTopicYN="N">Cryopreservation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011664" MajorTopicYN="Y">Pulmonary Valve</DescriptorName><QualifierName UI="Q000637" MajorTopicYN="N">transplantation</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012756" MajorTopicYN="N">Sheep</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014184" MajorTopicYN="N">Transplantation, Homologous</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Cell repopulation</Keyword><Keyword MajorTopicYN="N">Cryopreservation</Keyword><Keyword MajorTopicYN="N">Decellularization</Keyword><Keyword MajorTopicYN="N">Homografts</Keyword><Keyword MajorTopicYN="N">Remodelling</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2021</Year><Month>3</Month><Day>9</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2021</Year><Month>7</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>8</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2022</Year><Month>5</Month><Day>27</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>8</Month><Day>28</Day><Hour>12</Hour><Minute>12</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">34453660</ArticleId><ArticleId IdType="doi">10.1007/s10561-021-09948-2</ArticleId><ArticleId IdType="pii">10.1007/s10561-021-09948-2</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Ali ML, Kumar SP, Bjornstad K, Duran CM (1996) The sheep as an animal model for heart valve research. 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Increasing the post-mortem ischaemic harvesting time beyond 24 h increases the potential donor pool. Cryopreservation, routinely used to preserve homografts, damages the extracellular matrix (ECM), contributing to valve degeneration. Decellularization might preserve the ECM, promoting host-cell infiltration and contributing towards better clinical outcomes. This study compared the performance of cryopreserved versus decellularized pulmonary homografts in the right ventricle outflow tract (RVOT) of a juvenile ovine model. Homografts (n = 10) were harvested from juvenile sheep, subjected to 48 h post-mortem cold ischaemia, cryopreserved or decellularized and implanted in the RVOT of juvenile sheep for 180 days. Valve performance was monitored echocardiographically. Explanted leaflet and wall tissue evaluated histologically, on electron microscopical appearance, mechanical properties and calcium content. In both groups the annulus diameter increased. Cryopreserved homografts developed significant (¾) pulmonary regurgitation, with trivial regurgitation (¼) in the decellularized group. Macroscopically, explanted cryopreserved valve leaflets retracted and thickened while decellularized leaflets remained thin and pliable with good coaptation. Cryopreserved leaflets and walls demonstrated loss of interstitial cells with collapsed collagen, and decellularized scaffolds extensive, uniform ingrowth of host-cells with an intact collagen network. Calcific deposits were shown only in leaflets and walls of cryopreserved explants. Young fibroblasts, with vacuoles and rough endoplasmic reticulum in the cytoplasm, repopulated the leaflets and walls of decellularized scaffolds. Young's modulus of wall tissue in both groups increased significantly. Cryopreserved valves deteriorate over time due to loss of cellularity and calcification, while decellularized scaffolds demonstrated host-cell repopulation, structural maintenance, tissue remodelling and growth potential.<CopyrightInformation>© 2021. The Author(s), under exclusive licence to Springer Nature B.V.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>van den Heever</LastName><ForeName>Johannes Jacobus</ForeName><Initials>JJ</Initials><Identifier Source="ORCID">0000-0001-6905-1779</Identifier><AffiliationInfo><Affiliation>Department of Cardiothoracic Surgery, Faculty of Health Sciences, Internal Box G32), University of the Free State (UFS), P.O. Box 339, Bloemfontein, 9300, South Africa. vdheeverjj@ufs.ac.za.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jordaan</LastName><ForeName>Christiaan Johannes</ForeName><Initials>CJ</Initials><AffiliationInfo><Affiliation>Department of Cardiothoracic Surgery, Faculty of Health Sciences, Internal Box G32), University of the Free State (UFS), P.O. Box 339, Bloemfontein, 9300, South Africa.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lewies</LastName><ForeName>Angelique</ForeName><Initials>A</Initials><Identifier Source="ORCID">0000-0002-5624-1386</Identifier><AffiliationInfo><Affiliation>Department of Cardiothoracic Surgery, Faculty of Health Sciences, Internal Box G32), University of the Free State (UFS), P.O. Box 339, Bloemfontein, 9300, South Africa.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bester</LastName><ForeName>Dreyer</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Cardiothoracic Surgery, Faculty of Health Sciences, Internal Box G32), University of the Free State (UFS), P.O. Box 339, Bloemfontein, 9300, South Africa.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Goedhals</LastName><ForeName>Jacqueline</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Anatomical Pathology, Faculty of Health Sciences, University of the Free State (UFS), P.O. Box 339, Bloemfontein, 9300, South Africa.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Botes</LastName><ForeName>Lezelle</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Health Sciences, Central University of Technology, Free State (CUT), Private Bag X20539, Bloemfontein, 9300, South Africa.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dohmen</LastName><ForeName>Pascal Maria</ForeName><Initials>PM</Initials><AffiliationInfo><Affiliation>Department of Cardiothoracic Surgery, Faculty of Health Sciences, Internal Box G32), University of the Free State (UFS), P.O. Box 339, Bloemfontein, 9300, South Africa.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Klinik und Poliklinik für Herzchirurgie, Klinikdirektor (K), Universitätsmedizin Rostock, Schillingallee 35, 18057, Rostock, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Smit</LastName><ForeName>Francis Edwin</ForeName><Initials>FE</Initials><AffiliationInfo><Affiliation>Department of Cardiothoracic Surgery, Faculty of Health Sciences, Internal Box G32), University of the Free State (UFS), P.O. Box 339, Bloemfontein, 9300, South Africa.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D003160">Comparative Study</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>08</Month><Day>28</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Cell Tissue Bank</MedlineTA><NlmUniqueID>100965121</NlmUniqueID><ISSNLinking>1389-9333</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>9007-34-5</RegistryNumber><NameOfSubstance UI="D003094">Collagen</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D064591" MajorTopicYN="N">Allografts</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003094" MajorTopicYN="N">Collagen</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015925" MajorTopicYN="N">Cryopreservation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011664" MajorTopicYN="Y">Pulmonary Valve</DescriptorName><QualifierName UI="Q000637" MajorTopicYN="N">transplantation</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012756" MajorTopicYN="N">Sheep</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014184" MajorTopicYN="N">Transplantation, Homologous</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Cell repopulation</Keyword><Keyword MajorTopicYN="N">Cryopreservation</Keyword><Keyword MajorTopicYN="N">Decellularization</Keyword><Keyword MajorTopicYN="N">Homografts</Keyword><Keyword MajorTopicYN="N">Remodelling</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2021</Year><Month>3</Month><Day>9</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2021</Year><Month>7</Month><Day>25</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>8</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2022</Year><Month>5</Month><Day>27</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>8</Month><Day>28</Day><Hour>12</Hour><Minute>12</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">34453660</ArticleId><ArticleId IdType="doi">10.1007/s10561-021-09948-2</ArticleId><ArticleId IdType="pii">10.1007/s10561-021-09948-2</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Ali ML, Kumar SP, Bjornstad K, Duran CM (1996) The sheep as an animal model for heart valve research. 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Front Cardiovasc Med 6:72. https://doi.org/10.3389/fcvm.2019.00072</Citation><ArticleIdList><ArticleId IdType="doi">10.3389/fcvm.2019.00072</ArticleId><ArticleId IdType="pubmed">31231661</ArticleId><ArticleId IdType="pmc">6566127</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">34453587</PMID><DateRevised><Year>2021</Year><Month>08</Month><Day>28</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1432-0711</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2021</Year><Month>Aug</Month><Day>28</Day></PubDate></JournalIssue><Title>Archives of gynecology and obstetrics</Title><ISOAbbreviation>Arch Gynecol Obstet</ISOAbbreviation></Journal><ArticleTitle>Prenatal diagnosis, associated findings and postnatal outcome of fetuses with truncus arteriosus communis (TAC).</ArticleTitle><ELocationID EIdType="doi" ValidYN="Y">10.1007/s00404-021-06157-w</ELocationID><Abstract><AbstractText Label="PURPOSE" NlmCategory="OBJECTIVE">To assess the spectrum of associated anomalies, the intrauterine course, postnatal outcome and management of fetuses with truncus arteriosus communis (TAC) METHODS: All cases of TAC diagnosed prenatally over a period of 8 years were retrospectively collected in two tertiary referral centers. All additional prenatal findings were assessed and correlated with the outcome. The accuracy of prenatal diagnosis was assessed.<AbstractText Label="RESULTS" NlmCategory="RESULTS">39 cases of TAC were diagnosed prenatally. Mean gestational age at first diagnosis was 22 weeks (range, 13-38). Two cases were lost follow-up. Correct prenatal diagnosis of TAC was made in 21 of 24 (87.5%) cases and of TAC subtype in 19 of 21 (90.5%) cases. Prenatal diagnosis of TAC was incorrect in three cases: one newborn had aortic atresia with ventricular septal defect postnatally, one had hypoplastic right ventricle with dextro Transposition of the Great Arteries with coartation of the aorta and a third newborn had Tetralogy of Fallot with abnormal origin of the left pulmonary artery arising from the ascending aorta postnatally. These three cases were excluded from further analysis. In 9 of 34 (26.5%) cases, TAC was an isolated finding. 13 (38.2%) fetuses had additional chromosomal anomalies. Among them, microdeletion 22q11.2 was most common with a prevalence of 17.6% in our cohort. Another 3 fetuses were highly suspicious for non-chromosomal genetic syndromes due to their additional extra-cardiac anomalies, but molecular diagnosis could not be provided. Major cardiac and extra-cardiac anomalies occurred in 3 (8.8%) and in 20 (58.8%) cases, respectively. Predominantly, extra-cardiac anomalies occurred in association with chromosomal anomalies. Additionally, severe IUGR occurred in 6 (17.6%) cases. There were 14 terminations of pregnancy (41.2%), 1 (2.9%) intrauterine fetal death, 5 postnatal deaths (14.7%) and 14 (41.2%) infants were alive at last follow-up. Intention-to-treat survival rate was 70%. Mean follow-up among survivors was 42 months (range, 6-104). Postoperative health status among survivors was excellent in 11 (78.6%) infants, but 5 (46.2%) of them needed repeated re-interventions due to recurrent pulmonary artery or conduit stenosis. The other 3 (21.4%) survivors were significantly impaired due to non-cardiac problems.<AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">TAC is a rare and complex cardiac anomaly that can be diagnosed prenatally with high precision. TAC is frequently associated with chromosomal and extra-cardiac anomalies, leading to a high intrauterine and postnatal loss rate due to terminations and perioperative mortality. Without severe extra-cardiac anomalies, postoperative short- and medium-term health status is excellent, independent of the subtype of TAC, but the prevalence of repeated interventions due to recurrent stenosis is high. |
2,331,082 | Intervention of Brain-Derived Neurotrophic Factor and Other Neurotrophins in Adult Neurogenesis. | Cell survival during adult neurogenesis and the modulation of each step, namely, proliferation, lineage differentiation, migration, maturation, and functional integration of the newborn cells into the existing circuitry, is regulated by intrinsic and extrinsic factors. Transduction of extracellular niche signals triggers the activation of intracellular mechanisms that regulate adult neurogenesis by affecting gene expression. While the intrinsic factors include transcription factors and epigenetic regulators, the extrinsic factors are molecular signals that are present in the neurogenic niche microenvironment. These include morphogens, growth factors, neurotransmitters, and signaling molecules secreted as soluble factors or associated to the extracellular matrix. Among these molecular mechanisms are neurotrophins and neurotrophin receptors which have been implicated in the regulation of adult neurogenesis at different levels, with brain-derived neurotrophic factor (BDNF) being the most studied neurotrophin. In this chapter, we review the current knowledge about the role of neurotrophins in the regulation of adult neurogenesis in both the subventricular zone (SVZ) and the hippocampal subgranular zone (SGZ). |
2,331,083 | An Overview of Adult Neurogenesis. | Neurogenesis is maintained in the mammalian brain throughout adulthood in two main regions: the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the hippocampal dentate gyrus. Adult neurogenesis is a process composed of multiple steps by which neurons are generated from dividing adult neural stem cells and migrate to be integrated into existing neuronal circuits. Alterations in any of these steps impair neurogenesis and may compromise brain function, leading to cognitive impairment and neurodegenerative diseases. Therefore, understanding the cellular and molecular mechanisms that modulate adult neurogenesis is the centre of attention of regenerative research. In this chapter, we review the main properties of the adult neurogenic niches. |
2,331,084 | Microinjection of Reelin into the mPFC prevents MK-801-induced recognition memory impairment in mice. | Reelin, a large extracellular matrix protein, helps to regulate neuronal plasticity and cognitive function. Several studies have shown that Reelin dysfunction, resulting from factors such as mutations in gene RELN or low Reelin expression, is associated with schizophrenia (SCZ). We previously reported that microinjection of Reelin into cerebral ventricle prevents phencyclidine-induced cognitive and sensory-motor gating deficits. However, it remains unclear whether and how Reelin ameliorates behavioral abnormalities in the animal model of SCZ. In the present study, we evaluated the effect of recombinant Reelin microinjection into the medial prefrontal cortex (mPFC) on abnormal behaviors induced by MK-801, an N-methyl-D-aspartate receptor antagonist. Microinjection of Reelin into the mPFC prevented impairment of recognition memory of MK-801-treated mice in the novel object recognition test (NORT). On the other hand, the same treatment had no effect on deficits in sensory-motor gating and short-term memory in the pre-pulse inhibition and Y-maze tests, respectively. To establish the neural substrates that respond to Reelin, the number of c-Fos-positive cells in the mPFC was determined. A significant increase in c-Fos-positive cells in the mPFC of MK-801-treated mice was observed when compared with saline-treated mice, and this change was suppressed by microinjection of Reelin into the mPFC. A K2360/2467A Reelin that cannot bind to its receptor failed to ameliorate MK-801-induced cognitive deficits in NORT. These results suggest that Reelin prevents MK-801-induced recognition memory impairment by acting on its receptors to suppress neural activity in the mPFC of mice. |
2,331,085 | Strictly third ventricle craniopharyngiomas: pathological verification, anatomo-clinical characterization and surgical results from a comprehensive overview of 245 cases. | The strictly third ventricle craniopharyngioma topography (strictly 3V CP) defines the subgroup of lesions developed above an anatomically intact third ventricle floor (3VF). The true existence of this exceedingly rare topographical category is highly controversial owing to the presumed embryological CP origin from Rathke's pouch, a structure developmentally situated outside the neural tube. This study thoroughly analyzes the largest series of strictly 3V CPs ever collected. From 5346 CP reports published between 1887 and 2021, we selected 245 cases with reliable pathological, surgical, and/or neuroradiological verification of an intact 3VF beneath the tumor. This specific topography occurs predominantly in adult (92.6%), male (64.4%) patients presenting with headache (69.2%), and psychiatric disturbances (59.2%). Neuroradiological features defining strictly 3V CPs are a tumor-free chiasmatic cistern (95.9%), an entirely visible pituitary stalk (86.4%), and the hypothalamus positioned around the tumor's lower pole (92.6%). Most are squamous papillary (82%), showing low-risk severity adhesions to the hypothalamus (74.2%). The adamantinomatous variant, however, associates a higher risk of severe hypothalamic adhesion (p < .001). High-risk attachments are also associated with psychiatric symptoms (p = .013), which represented the major predictor for unfavorable prognoses (83.3% correctly predicted) among cases operated from 2006 onwards. CP recurrence is associated with infundibulo-tuberal symptoms (p = .036) and incomplete surgical removal (p = .02). The exclusive demographic, clinico-pathological and neuroradiological characteristics of strictly 3V CPs make them a separate, unique topographical category. Accurately distinguishing strictly 3V CPs preoperatively from those tumors replacing the infundibulum and/or tuber cinereum (infundibulo-tuberal or not strictly 3V CPs) is critical for proper, judicious surgical planning. |
2,331,086 | Effects of catechin on a rodent model of autism spectrum disorder: implications for the role of nitric oxide in neuroinflammatory pathway. | The present research work aims at deciphering the involvement of nitric oxide pathway and its modulation by ( ±)catechin hydrate in experimental paradigm of autism spectrum disorders (ASD).</AbstractText>An intracerebroventricular infusion of 4 μl of 1 M propanoic acid was given in the anterior region of the lateral ventricle to induce autism-like phenotype in male rats. Oral administration of ( ±)catechin hydrate (25, 50, and 100 mg/kg) was initiated from the 3rd day lasting till the 28th day. L-NAME (50 mg/kg) and L-arginine (800 mg/kg) were also given individually as well as in combination to explore the ability of ( ±)catechin hydrate to act via nitric oxide pathway. Behavior test for sociability, stereotypy, anxiety, depression, and novelty, repetitive, and perseverative behavior was carried out between the 14th and 28th day. On the 29th day, animals were sacrificed, and levels of mitochondrial complexes and oxidative stress parameters were evaluated. We also estimated the levels of neuroinflammatory and apoptotic markers such as TNF-α, IL-6, NF-κB, IFN-γ, HSP-70, and caspase-3. To evaluate the involvement of nitric oxide pathway, the levels of iNOS and homocysteine were estimated.</AbstractText>Treatment with ( ±)catechin hydrate significantly ameliorated behavioral, biochemical, neurological, and molecular deficits. Hence, ( ±)catechin hydrate has potential to be used as neurotherapeutic agent in ASD targeting nitric oxide pathway-mediated oxidative and nitrosative stress responsible for behavioral, biochemical, and molecular alterations via modulating nitric oxide pathway.</AbstractText>The evaluation of the levels of iNOS and homocysteine conclusively establishes the role of nitric oxide pathway in causing behavioral, biochemical, and molecular deficits and the beneficial effect of ( ±)catechin hydrate in restoring these alterations.</AbstractText>© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</CopyrightInformation> |
2,331,087 | Post-hemorrhagic ventricular dilatation affects white matter maturation in extremely preterm infants. | Data on microstructural white matter integrity in preterm infants with post-hemorrhagic ventricular dilatation (PHVD) using diffusion tensor imaging (DTI) are limited. Also, to date, no study has focused on the DTI changes in extremely preterm (EP) infants with PHVD.</AbstractText>A case-control study of EP infants <28 weeks' gestation with PHVD was conducted. Diffusivity and fractional anisotropy (FA) values of corticospinal tracts (CST) and corpus callosum (CC) were measured using DTI at term-equivalent age. Outcomes were assessed at 2-years-corrected age.</AbstractText>Twenty-one infants with PHVD and 21 matched-controls were assessed. FA values in the CC were lower in infants with PHVD compared with controls (mean difference, 0.05 [95% confidence interval (CI), 0.02-0.08], p < 0.001). In infants with periventricular hemorrhagic infarction, FA values in the CC were lower than in controls (mean difference, 0.05 [95% CI, 0.02-0.09], p = 0.005). The composite cognitive and motor scores were associated with the FA value of the CC (coefficient 114, p = 0.01 and coefficient 147, p = 0.004; respectively).</AbstractText>Extremely preterm infants with PHVD showed lower FA values in CC. A positive correlation was also shown between the composite cognitive and motor scores and FA value of the CC at 2-years-corrected age.</AbstractText>Extremely preterm infants with post-hemorrhagic ventricular dilatation showed lower fractional anisotropy values in their corpus callosum compared with controls reflecting the impaired microstructure of these commissural nerve fibers that are adjacent to the dilated ventricles. Impaired microstructure of the corpus callosum was shown to be associated with cognitive and motor scores at 2-years-corrected age.</AbstractText>© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.</CopyrightInformation> |
2,331,088 | Spaceflight Modulates the Expression of Key Oxidative Stress and Cell Cycle Related Genes in Heart. | Spaceflight causes cardiovascular changes due to microgravity-induced redistribution of body fluids and musculoskeletal unloading. Cardiac deconditioning and atrophy on Earth are associated with altered <i>Trp53</i> and oxidative stress-related pathways, but the effects of spaceflight on cardiac changes at the molecular level are less understood. We tested the hypothesis that spaceflight alters the expression of key genes related to stress response pathways, which may contribute to cardiovascular deconditioning during extended spaceflight. Mice were exposed to spaceflight for 15 days or maintained on Earth (ground control). Ventricle tissue was harvested starting ~3 h post-landing. We measured expression of select genes implicated in oxidative stress pathways and <i>Trp53</i> signaling by quantitative PCR. Cardiac expression levels of 37 of 168 genes tested were altered after spaceflight. Spaceflight downregulated transcription factor, <i>Nfe2l2 (Nrf2)</i>, upregulated <i>Nox1</i> and downregulated <i>Ptgs2</i>, suggesting a persistent increase in oxidative stress-related target genes. Spaceflight also substantially upregulated <i>Cdkn1a</i> (<i>p21</i>) and cell cycle/apoptosis-related gene <i>Myc</i>, and downregulated the inflammatory response gene <i>Tnf</i>. There were no changes in apoptosis-related genes such as <i>Trp53</i>. Spaceflight altered the expression of genes regulating redox balance, cell cycle and senescence in cardiac tissue of mice. Thus, spaceflight may contribute to cardiac dysfunction due to oxidative stress. |
2,331,089 | OTX2 Homeoprotein Functions in Adult Choroid Plexus. | The choroid plexus is an important blood barrier that secretes cerebrospinal fluid, which essential for embryonic brain development and adult brain homeostasis. The OTX2 homeoprotein is a transcription factor that is critical for choroid plexus development and remains highly expressed in adult choroid plexus. Through RNA sequencing analyses of constitutive and conditional knockdown adult mouse models, we reveal putative functional roles for OTX2 in adult choroid plexus function, including cell signaling and adhesion, and show that OTX2 regulates the expression of factors that are secreted into the cerebrospinal fluid, notably transthyretin. We also show that <i>Otx2</i> expression impacts choroid plexus immune and stress responses, and affects splicing, leading to changes in the mRNA isoforms of proteins that are implicated in the oxidative stress response and DNA repair. Through mass spectrometry analysis of OTX2 protein partners in the choroid plexus, and in known non-cell-autonomous target regions, such as the visual cortex and subventricular zone, we identify putative targets that are involved in cell adhesion, chromatin structure, and RNA processing. Thus, OTX2 retains important roles for regulating choroid plexus function and brain homeostasis throughout life. |
2,331,090 | ExpressHeart: Web Portal to Visualize Transcriptome Profiles of Non-Cardiomyocyte Cells. | Unveiling the molecular features in the heart is essential for the study of heart diseases. Non-cardiomyocytes (nonCMs) play critical roles in providing structural and mechanical support to the working myocardium. There is an increasing amount of single-cell RNA-sequencing (scRNA-seq) data characterizing the transcriptomic profiles of nonCM cells. However, no tool allows researchers to easily access the information. Thus, in this study, we develop an open-access web portal, ExpressHeart, to visualize scRNA-seq data of nonCMs from five laboratories encompassing three species. ExpressHeart enables comprehensive visualization of major cell types and subtypes in each study; visualizes gene expression in each cell type/subtype in various ways; and facilitates identifying cell-type-specific and species-specific marker genes. ExpressHeart also provides an interface to directly combine information across datasets, for example, generating lists of high confidence DEGs by taking the intersection across different datasets. Moreover, ExpressHeart performs comparisons across datasets. We show that some homolog genes (e.g., <i>Mmp14</i> in mice and <i>mmp14b</i> in zebrafish) are expressed in different cell types between mice and zebrafish, suggesting different functions across species. We expect ExpressHeart to serve as a valuable portal for investigators, shedding light on the roles of genes on heart development in nonCM cells. |
2,331,091 | GSH and Zinc Supplementation Attenuate Cadmium-Induced Cellular Stress and Stimulation of Choline Uptake in Cultured Neonatal Rat Choroid Plexus Epithelia. | Choroid plexus (CP) sequesters cadmium and other metals, protecting the brain from these neurotoxins. These metals can induce cellular stress and modulate homeostatic functions of CP, such as solute transport. We previously showed in primary cultured neonatal rat CP epithelial cells (CPECs) that cadmium induced cellular stress and stimulated choline uptake at the apical membrane, which interfaces with cerebrospinal fluid in situ. Here, in CPECs, we characterized the roles of glutathione (GSH) and Zinc supplementation in the adaptive stress response to cadmium. Cadmium increased GSH and decreased the reduced GSH-to-oxidized GSH (GSSG) ratio. Heat shock protein-70 (Hsp70), heme oxygenase (HO-1), and metallothionein (Mt-1) were induced along with the catalytic and modifier subunits of glutamate cysteine ligase (GCL), the rate-limiting enzyme in GSH synthesis. Inhibition of GCL by l-buthionine sulfoximine (BSO) enhanced stress protein induction and stimulation of choline uptake by cadmium. Zinc alone did not induce Hsp70, HO-1, or GCL subunits, or modulate choline uptake. Zinc supplementation during cadmium exposure attenuated stress protein induction and stimulation of choline uptake; this effect persisted despite inhibition of GSH synthesis. These data indicated up-regulation of GSH synthesis promotes adaptation to cadmium-induced cellular stress in CP, but Zinc may confer cytoprotection independent of GSH. |
2,331,092 | Preterm Intraventricular Hemorrhage-Induced Inflammatory Response in Human Choroid Plexus Epithelial Cells. | Following an intraventricular hemorrhage (IVH), red blood cell lysis and hemoglobin (Hb) oxidation with the release of heme can cause sterile neuroinflammation. In this study, we measured Hb derivates and cellular adhesion molecules ICAM-1 and VCAM-1 with cell-free miRNAs in cerebrospinal fluid (CSF) samples obtained from Grade-III and Grade-IV preterm IVH infants (IVH-III and IVH-IV, respectively) at multiple time points between days 0-60 after the onset of IVH. Furthermore, human choroid plexus epithelial cells (HCPEpiCs) were incubated with IVH and non-IVH CSF (10 <i>v</i>/<i>v</i> %) for 24 h in vitro to investigate the IVH-induced inflammatory response that was investigated via: (i) HMOX1, IL8, VCAM1, and ICAM1 mRNAs as well as miR-155, miR-223, and miR-181b levels by RT-qPCR; (ii) nuclear translocation of the NF-κB p65 subunit by fluorescence microscopy; and (iii) reactive oxygen species (ROS) measurement. We found a time-dependent alteration of heme, IL-8, and adhesion molecules which revealed a prolonged elevation in IVH-IV vs. IVH-III with higher miR-155 and miR-181b expression at days 41-60. Exposure of HCPEpiCs to IVH CSF samples induced HMOX1, IL8, and ICAM1 mRNA levels along with increased ROS production via the NF-κB pathway activation but without cell death, as confirmed by the cell viability assay. Additionally, the enhanced intracellular miR-155 level was accompanied by lower miR-223 and miR-181b expression in HCPEpiCs after CSF treatment. Overall, choroid plexus epithelial cells exhibit an abnormal cell phenotype after interaction with pro-inflammatory CSF of IVH origin which may contribute to the development of later clinical complications in preterm IVH. |
2,331,093 | Shunt Overdrainage: Reappraisal of the Syndrome and Proposal for an Integrative Model. | Although shunt overdrainage is a well-known complication in hydrocephalus management, the problem has been underestimated. Current literature suggests that the topic requires more examination. An insight into this condition is limited by a lack of universally agreed-upon diagnostic criteria, heterogeneity of published series, the multitude of different management options and misunderstanding of relationships among pathophysiological mechanisms involved. We carried out a review of the literature on clinical, radiological, intracranial pressure (ICP), pathophysiological and treatment concepts to finally propose an integrative model. Active prophylaxis and management are proposed according to this model based on determination of pathophysiological mechanisms and predisposing factors behind each individual case. As pathophysiology is progressively multifactorial, prevention of siphoning with gravitational valves or antisiphon devices is mandatory to avoid or minimize further complications. Shunt optimization or transferal and neuroendoscopy may be recommended when ventricular collapse and cerebrospinal fluid isolation appear. Cranial expansion may be useful in congenital or acquired craniocerebral disproportion and shunting the subarachnoid space in communicating venous hydrocephalus and idiopathic intracranial hypertension. |
2,331,094 | Diversity of Adult Neural Stem and Progenitor Cells in Physiology and Disease. | Adult neural stem and progenitor cells (NSPCs) contribute to learning, memory, maintenance of homeostasis, energy metabolism and many other essential processes. They are highly heterogeneous populations that require input from a regionally distinct microenvironment including a mix of neurons, oligodendrocytes, astrocytes, ependymal cells, NG2+ glia, vasculature, cerebrospinal fluid (CSF), and others. The diversity of NSPCs is present in all three major parts of the CNS, i.e., the brain, spinal cord, and retina. Intrinsic and extrinsic signals, e.g., neurotrophic and growth factors, master transcription factors, and mechanical properties of the extracellular matrix (ECM), collectively regulate activities and characteristics of NSPCs: quiescence/survival, proliferation, migration, differentiation, and integration. This review discusses the heterogeneous NSPC populations in the normal physiology and highlights their potentials and roles in injured/diseased states for regenerative medicine. |
2,331,095 | Cumulative Damage: Cell Death in Posthemorrhagic Hydrocephalus of Prematurity. | Globally, approximately 11% of all infants are born preterm, prior to 37 weeks' gestation. In these high-risk neonates, encephalopathy of prematurity (EoP) is a major cause of both morbidity and mortality, especially for neonates who are born very preterm (<32 weeks gestation). EoP encompasses numerous types of preterm birth-related brain abnormalities and injuries, and can culminate in a diverse array of neurodevelopmental impairments. Of note, posthemorrhagic hydrocephalus of prematurity (PHHP) can be conceptualized as a severe manifestation of EoP. PHHP impacts the immature neonatal brain at a crucial timepoint during neurodevelopment, and can result in permanent, detrimental consequences to not only cerebrospinal fluid (CSF) dynamics, but also to white and gray matter development. In this review, the relevant literature related to the diverse mechanisms of cell death in the setting of PHHP will be thoroughly discussed. Loss of the epithelial cells of the choroid plexus, ependymal cells and their motile cilia, and cellular structures within the glymphatic system are of particular interest. Greater insights into the injuries, initiating targets, and downstream signaling pathways involved in excess cell death shed light on promising areas for therapeutic intervention. This will bolster current efforts to prevent, mitigate, and reverse the consequential brain remodeling that occurs as a result of hydrocephalus and other components of EoP. |
2,331,096 | Depletion of Alpha-Melanocyte-Stimulating Hormone Induces Insatiable Appetite and Gains in Energy Reserves and Body Weight in Zebrafish. | The functions of anorexigenic neurons secreting proopiomelanocortin (POMC)/alpha-melanocyte-stimulating hormone (α-MSH) of the melanocortin system in the hypothalamus in vertebrates are energy homeostasis, food intake, and body weight regulation. However, the mechanisms remain elusive. This article reports on zebrafish that have been genetically engineered to produce α-MSH mutants, α-MSH<sup>-7aa</sup> and α-MSH<sup>-8aa</sup>, selectively lacking 7 and 8 amino acids within the α-MSH region, but retaining most of the other normal melanocortin-signaling (Pomc-derived) peptides. The α-MSH mutants exhibited hyperphagic phenotypes leading to body weight gain, as observed in human patients and mammalian models. The actions of several genes regulating appetite in zebrafish are similar to those in mammals when analyzed using gene expression analysis. These include four selected orexigenic genes: Promelanin-concentrating hormone (<i>pmch</i>), agouti-related protein 2 (<i>agrp2</i>), neuropeptide Y (<i>npy</i>), and hypothalamic hypocretin/orexin (<i>hcrt</i>). We also study five selected anorexigenic genes: Brain-derived neurotrophic factor (<i>bdnf</i>), single-minded homolog 1-a (<i>sim1a</i>), corticotropin-releasing hormone b (<i>crhb</i>), thyrotropin-releasing hormone (<i>trh</i>), and prohormone convertase 2 (<i>pcsk2</i>). The orexigenic actions of α-MSH mutants are rescued completely after hindbrain ventricle injection with a synthetic analog of α-MSH and a melanocortin receptor agonist, Melanotan II. We evaluate the adverse effects of MSH depletion on energy balance using the Alamar Blue metabolic rate assay. Our results show that α-MSH is a key regulator of POMC signaling in appetite regulation and energy expenditure, suggesting that it might be a potential therapeutic target for treating human obesity. |
2,331,097 | Identification of Reference Genes for Circadian Studies on Brain Microvessels and Choroid Plexus Samples Isolated from Rats. | Delivery of putative compounds of therapeutic value to the brain is limited by brain barriers: the blood-brain barrier located in the endothelium of the brain microvessels (BrMVs) and the blood-cerebrospinal fluid barrier located in the epithelium of the choroid plexus (ChP). Understanding their function and modulation by the circadian clock may enhance the efficacy of brain-targeting therapies. The aim of the present study was to evaluate the stability of 10 reference genes in the BrMV and ChP, isolated from male and female rats at six time points (ZT1, 5, 9, 13, 17, and 21). Gene evaluations were performed by qPCR, analyzed by RefFinder tool, and verified by analyzing the expression of the brain and muscle ARNT-like 1 (<i>Bmal1</i>) using the qPCR and digital PCR methods. We identified as the most stable genes for circadian studies tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (<i>Ywhaz</i>) and apolipoprotein E (<i>Apoe</i>) for BrMV, and beta actin (<i>Actb</i>) and hypoxanthine-guanine phosphoribosyltransferase (<i>Hprt1</i>) for ChP. After verification, ribosomal protein (<i>Rps18</i>) was also included as a sufficient reference gene. Additionally, the observed gender difference in the <i>Bmal1</i> oscillations in both BrMV and ChP suggests that separate studies for each gender are recommended. |
2,331,098 | Sarcotubular Myopathy Due to Novel <i>TRIM32</i> Mutation in Association with Multiple Sclerosis. | Azerbaijani 28-year-old female showed weakness (MRC (Medical Research Council Scale for Muscle Strength) grade 4 in the proximal part of the upper and MRC grade 2-3 in the lower extremities), difficulty in stair lifting, positive symptom of Hoover's rising, «waddling gait», decline deep reflexes symmetrical, lack of surface reflexes, positive Babinsky's reflex on the right, urinary incontinence during sneezing, prolonged walking and exercise from puberty. Additional methods made it possible to identify minor violations of conduction of the left ventricle, electromyography signs of primary muscular disease with predominant involvement of the proximal muscles of the lower extremities, elevation of serum creatine kinase (746.81 U/l), active foci of demyelination in the left frontal lobe, intrathecal synthesis of oligoclonal IgG bands (type 2) in cerebrospinal fluid, atrophy and fatty degeneration of all muscles of the shins, homozygous Variant of Uncertain Significance (VUS) c.1855C > T (p.Pro619Ser) in <i>TRIM32</i> gene and heterozygous VUS c.2300C > G (p.Thr767Arg) in <i>KIF5A</i>, c.2840G > A (p.Arg947Lys) in <i>MYH2</i>, c.1502G > C (p.Gly501Ala) in <i>POMT1</i> genes. Comparison of the phenotypes of the mutations that have been identified with the clinical picture of the patient suggests that VUS c.1855C > T (p.Pro619Ser) in the <i>TRIM32</i> gene can be pathological. Summarizing, it can be argued that the cause of the identified disorders is a homozygous variant c.1855C > T (p.Pro619Ser) in <i>TRIM32</i> gene that causes LGMDR8 in a patient with MS. |
2,331,099 | Role of Two-Dimensional Speckle-Tracking Echocardiography in Early Detection of Left Ventricular Dysfunction in Dogs. | Two-dimensional speckle-tracking echocardiography (2D-STE) is an advanced echocardiographic technique based on deformation imaging that allows comprehensive evaluation of the myocardial function. Clinical application of 2D-STE holds great potential for its ability to provide valuable information on both global and regional myocardial function and to quantify cardiac rotation and synchronicity, which are not readily possible with the conventional echocardiography. It has gained growing importance over the past decade, especially in human medicine, and its application includes assessment of myocardial function, detection of subclinical myocardial dysfunction and serving as a prognostic indicator. This review illustrates the fundamental concepts of deformation analysis and gives an overview of the current understanding and its clinical application of this technique in veterinary medicine, with a focus on early detection of left ventricular (LV) dysfunction in dogs. |
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